advertisement
Browse Health
Internist, Pulmonologist (lungs)
24 years of experience

Credentials

Education ?

Medical School Score Rankings
University of Washington (1988)
  •  
Top 25%

Awards & Distinctions ?

Associations
American Board of Internal Medicine

Affiliations ?

Dr. Clark is affiliated with 4 hospitals.

Hospital Affiliations

Score

Rankings

  • Providence Alaska Medical Center
    Pulmonary Disease
    PO Box 196604, Anchorage, AK 99519
    •  
    Top 25%
  • Alaska Regional Hospital
    Pulmonary Disease
    2801 Debarr Rd, Anchorage, AK 99508
    •  
    Top 50%
  • Providence Extended Care Center
    4900 Eagle St, Anchorage, AK 99503
  • Pulmonary Associates
  • Publications & Research

    Dr. Clark has contributed to 250 publications.
    Title Four-year Weight Losses in the Look Ahead Study: Factors Associated with Long-term Success.
    Date March 2012
    Journal Obesity (silver Spring, Md.)
    Excerpt

    This report provides a further analysis of the year 4 weight losses in the Look AHEAD (Action for Health in Diabetes) study and identifies factors associated with long-term success. A total of 5,145 overweight/obese men and women with type 2 diabetes were randomly assigned to an intensive lifestyle intervention (ILI) or a usual care group, referred to as Diabetes Support and Education (DSE). ILI participants were provided approximately weekly group or individual treatment in year 1; continued but less frequent contact was provided in years 2-4. DSE participants received three group educational sessions in all years. As reported previously, at year 4, ILI participants lost an average of 4.7% of initial weight, compared with 1.1% for DSE (P < 0.0001). More ILI than DSE participants lost ≥ 5% (46% vs. 25%, P < 0.0001) and ≥ 10% (23% vs. 10%, P < 0.0001) of initial weight. Within the ILI, achievement of both the 5% and 10% categorical weight losses at year 4 was strongly related to meeting these goals at year 1. A total of 887 participants in ILI lost ≥ 10% at year 1, of whom 374 (42.2%) achieved this loss at year 4. Participants who maintained the loss, compared with those who did not, attended more treatment sessions and reported more favorable physical activity and food intake at year 4. These results provide critical evidence that a comprehensive lifestyle intervention can induce clinically significant weight loss (i.e., ≥ 5%) in overweight/obese participants with type 2 diabetes and maintain this loss in more than 45% of patients at 4 years.

    Title Advances in the Mode of Action of Pyrethroids.
    Date March 2012
    Journal Topics in Current Chemistry
    Excerpt

    The ability to clone, express, and electrophysiologically measure currents carried by voltage-gated ion channels has allowed a detailed assessment of the action of pyrethroids on various target proteins.Recently, the heterologous expression of various rat brain voltage-gated sodium channel isoforms in Xenopus laevis oocytes has determined a wide range of sensitivities to the pyrethroids, with some channels virtually insensitive and others highly sensitive. Furthermore, some isoforms show selective sensitivity to certain pyrethroids and this selectivity can be altered in a state-dependent manner. Additionally, some rat brain isoforms are apparently more sensitive to pyrethroids than the corresponding human isoform. These finding may have significant relevance in judging the merit and value of assessing the risk of pyrethroid exposures to humans using toxicological studies done in rat.Other target sites for certain pyrethroids include the voltage-gated calcium and chloride channels. Of particular interest is the increased effect of Type II pyrethroids on certain phosphoforms of the N-type Ca(v)2.2 calcium channel following post-translational modification and its relationship to enhanced neurotransmitter release seen in vivo.Lastly, parallel neurobehavioral and mechanistic studies on three target sites suggest that a fundamental difference exists between the action of Types I and II pyrethroids, both on a functional and molecular level. These differences should be considered in any future risk evaluation of the pyrethroids.

    Title Hemochromatosis Gene and Nonalcoholic Fatty Liver Disease: a Systematic Review and Meta-analysis.
    Date March 2012
    Journal Journal of Hepatology
    Excerpt

    Previous studies examining the relationship between the C282Y and H63D HFE mutations and presence of nonalcoholic fatty liver disease (NAFLD) have yielded conflicting results. The goal of this study was to systematically evaluate and summarize data on the association between these two variants and the presence of NAFLD.

    Title Inhibitor of Kappa B Epsilon (iκbε) is a Non-redundant Regulator of C-rel-dependent Gene Expression in Murine T and B Cells.
    Date February 2012
    Journal Plos One
    Excerpt

    Inhibitors of kappa B (IκBs) -α, -β and -ε effect selective regulation of specific nuclear factor of kappa B (NF-κB) dimers according to cell lineage, differentiation state or stimulus, in a manner that is not yet precisely defined. Lymphocyte antigen receptor ligation leads to degradation of all three IκBs but activation only of subsets of NF-κB-dependent genes, including those regulated by c-Rel, such as anti-apoptotic CD40 and BAFF-R on B cells, and interleukin-2 (IL-2) in T cells. We report that pre-culture of a mouse T cell line with tumour necrosis factor-α (TNF) inhibits IL-2 gene expression at the level of transcription through suppressive effects on NF-κB, AP-1 and NFAT transcription factor expression and function. Selective upregulation of IκBε and suppressed nuclear translocation of c-Rel were very marked in TNF-treated, compared to control cells, whether activated via T cell receptor (TCR) pathway or TNF receptor. IκBε associated with newly synthesised c-Rel in activated cells and, in contrast to IκBα and -β, showed enhanced association with p65/c-Rel in TNF-treated cells relative to controls. Studies in IκBε-deficient mice revealed that basal nuclear expression and nuclear translocation of c-Rel at early time-points of receptor ligation were higher in IκBε-/- T and B cells, compared to wild-type. IκBε-/- mice exhibited increased lymph node cellularity and enhanced basal thymidine incorporation by lymphoid cells ex vivo. IκBε-/- T cell blasts were primed for IL-2 expression, relative to wild-type. IκBε-/- splenic B cells showed enhanced survival ex vivo, compared to wild-type, and survival correlated with basal expression of CD40 and induced expression of CD40 and BAFF-R. Enhanced basal nuclear translocation of c-Rel, and upregulation of BAFF-R and CD40 occurred despite increased IκBα expression in IκBε-/- B cells. The data imply that regulation of these c-Rel-dependent lymphoid responses is a non-redundant function of IκBε.

    Title Diagnostic Accuracy and Reliability of Ultrasonography for the Detection of Fatty Liver: a Meta-analysis.
    Date February 2012
    Journal Hepatology (baltimore, Md.)
    Excerpt

    Ultrasonography is a widely accessible imaging technique for the detection of fatty liver, but the reported accuracy and reliability have been inconsistent across studies. We aimed to perform a systematic review and meta-analysis of the diagnostic accuracy and reliability of ultrasonography for the detection of fatty liver. We used MEDLINE and Embase from October 1967 to March 2010. Studies that provided cross-tabulations of ultrasonography versus histology or standard imaging techniques, or that provided reliability data for ultrasonography, were included. Study variables were independently abstracted by three reviewers and double checked by one reviewer. Forty-nine (4720 participants) studies were included for the meta-analysis of diagnostic accuracy. The overall sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of ultrasound for the detection of moderate-severe fatty liver, compared to histology (gold standard), were 84.8% (95% confidence interval: 79.5-88.9), 93.6% (87.2-97.0), 13.3 (6.4-27.6), and 0.16 (0.12-0.22), respectively. The area under the summary receiving operating characteristics curve was 0.93 (0.91-0.95). Reliability of ultrasound for the detection of fatty liver showed kappa statistics ranging from 0.54 to 0.92 for intrarater reliability and from 0.44 to 1.00 for interrater reliability. Sensitivity and specificity of ultrasound was similar to that of other imaging techniques (i.e., computed tomography or magnetic resonance imaging). Statistical heterogeneity was present even after stratification for multiple clinically relevant characteristics. Conclusion: Ultrasonography allows for reliable and accurate detection of moderate-severe fatty liver, compared to histology. Because of its low cost, safety, and accessibility, ultrasound is likely the imaging technique of choice for screening for fatty liver in clinical and population settings.

    Title The Impact of Obesity on Breast Surgery Complications.
    Date December 2011
    Journal Plastic and Reconstructive Surgery
    Excerpt

    The increasing prevalence of obesity may worsen surgical outcomes and confound standardized metrics of surgical quality. Despite anecdotal evidence, the increased risk of complications in obese patients is not accounted for in these metrics. To better understand the impact of obesity on surgical complications, the authors designed a study to measure complication rates in obese patients presenting for a set of elective breast procedures.

    Title The Association of Arterial Shear and Flow-mediated Dilation in Diabetes.
    Date December 2011
    Journal Vascular Medicine (london, England)
    Excerpt

    While adjusting flow-mediated dilation (FMD), a measure of vascular function, for shear rate may be important when evaluating endothelial-dependent vasodilation, the relationship of FMD with shear rate in study populations with cardiovascular risk factors is unclear. We aimed to investigate the association of four measures of shear rate (peak shear rate (SR(peak)) and shear rate area under the curve through 30 seconds (SR(AUC 0-30)), 60 seconds (SR(AUC 0-60)), and time to peak dilation (SR(AUC 0-ttp))) with FMD in 50 study subjects with type 2 diabetes and mild hypertension undergoing baseline FMD testing for an exercise intervention trial. Associations among measures of shear rate and FMD were evaluated using Pearson's correlations and R(2). The four measures of shear rate were highly correlated within subjects, with Pearson's correlations ranging from 0.783 (p < 0.001) to 0.972 (p < 0.001). FMD was associated with each measure of shear rate, having a correlation of 0.576 (p < 0.001) with SR(AUC 0-30), 0.529 (p < 0.001) with SR(AUC 0-60), and 0.512 (p < 0.001) with SR(peak). Nine of 50 subjects (18%) did not dilate following the shear stimulus. Among the 41 responders, FMD had a correlation of 0.517 (p < 0.001) with SR(AUC 0-ttp) and similar correlations to those found in the full sample for SR(AUC 0-30), SR(AUC 0-60), and SR(peak). In conclusion, shear rate appears to explain up to a third of between-person variability in FMD response and our results support the reporting of shear rate and FMD with and without adjustment for shear rate in similar clinical populations with CVD risk factors.

    Title Morbidity Trajectories As Predictors of Utilization: Multi-year Disease Patterns in Taiwan's National Health Insurance Program.
    Date December 2011
    Journal Medical Care
    Excerpt

    Little is known about how morbidity levels progress over time and the implications of these morbidity trajectories for healthcare utilization.

    Title Surgical Site Infections and Cost in Obese Patients Undergoing Colorectal Surgery.
    Date November 2011
    Journal Archives of Surgery (chicago, Ill. : 1960)
    Excerpt

    To measure the effect of obesity on surgical site infection (SSI) rates and to define the cost of SSIs in patients undergoing colorectal surgery.

    Title Formation of Pbs Materials from Lead Xanthate Precursors.
    Date November 2011
    Journal Dalton Transactions (cambridge, England : 2003)
    Excerpt

    Six lead xanthate adducts Pb(S(2)COR)(2).L [R = Et, (n)Bu, L = bipy, TMEDA (tetramethylethylenediamine), PMDETA (pentamethyldiethylenetriamine)] have been synthesised and the structures of all, save Pb(S(2)COBu(n))(2).TMEDA (4) which is an oil, determined. Pb(S(2)COEt)(2).TMEDA (3) is seven-coordinate at lead through three chelating ligands and one weak intermolecular Pb‥S interaction. Both Pb(S(2)COR)(2).bipy [R = Et (1), (n)Bu (2)] are dimers in which one xanthate is terminal and the other μ(2) bridging at each sulphur, generating an eight-coordinate lead when the bipy donor is included. Both Pb(S(2)COR)(2).PMDETA [R = Et (5), (n)Bu (6)] are seven-coordinate at lead by virtue of two bidentate chelating xanthate ligands and a tridentate PMDETA; there are no intermolecular interactions. Trends in the (207)Pb NMR chemical shifts mirror the changes in the intramolecular coordination number across the series. Pb(S(2)COEt)(2).TMEDA (3) has been used to deposit PbS films on glass, Mo-coated glass and Si by AACVD. Pb(S(2)COEt)(2) also generated PbS nanocubes when decomposed under an autogenerated pressure.

    Title Genome-wide Association Analysis Identifies Variants Associated with Nonalcoholic Fatty Liver Disease That Have Distinct Effects on Metabolic Traits.
    Date August 2011
    Journal Plos Genetics
    Excerpt

    Nonalcoholic fatty liver disease (NAFLD) clusters in families, but the only known common genetic variants influencing risk are near PNPLA3. We sought to identify additional genetic variants influencing NAFLD using genome-wide association (GWA) analysis of computed tomography (CT) measured hepatic steatosis, a non-invasive measure of NAFLD, in large population based samples. Using variance components methods, we show that CT hepatic steatosis is heritable (∼26%-27%) in family-based Amish, Family Heart, and Framingham Heart Studies (n = 880 to 3,070). By carrying out a fixed-effects meta-analysis of genome-wide association (GWA) results between CT hepatic steatosis and ∼2.4 million imputed or genotyped SNPs in 7,176 individuals from the Old Order Amish, Age, Gene/Environment Susceptibility-Reykjavik study (AGES), Family Heart, and Framingham Heart Studies, we identify variants associated at genome-wide significant levels (p<5×10(-8)) in or near PNPLA3, NCAN, and PPP1R3B. We genotype these and 42 other top CT hepatic steatosis-associated SNPs in 592 subjects with biopsy-proven NAFLD from the NASH Clinical Research Network (NASH CRN). In comparisons with 1,405 healthy controls from the Myocardial Genetics Consortium (MIGen), we observe significant associations with histologic NAFLD at variants in or near NCAN, GCKR, LYPLAL1, and PNPLA3, but not PPP1R3B. Variants at these five loci exhibit distinct patterns of association with serum lipids, as well as glycemic and anthropometric traits. We identify common genetic variants influencing CT-assessed steatosis and risk of NAFLD. Hepatic steatosis associated variants are not uniformly associated with NASH/fibrosis or result in abnormalities in serum lipids or glycemic and anthropometric traits, suggesting genetic heterogeneity in the pathways influencing these traits.

    Title Comparison of the Humoral and Cellular Immune Responses Between Body and Head Lice Following Bacterial Challenge.
    Date July 2011
    Journal Insect Biochemistry and Molecular Biology
    Excerpt

    The differences in the immune response between body lice, Pediculus humanus humanus, and head lice, Pediculus humanus capitis, were investigated initially by measuring the proliferation rates of two model bacteria, a Gram-positive Staphylococcus aureus and a Gram-negative Escherichia coli, following challenge by injection. Body lice showed a significantly reduced immune response compared to head lice particularly to E. coli at the early stage of the immune challenge. Annotation of the body louse genome identified substantially fewer immune-related genes compared with other insects. Nevertheless, all required genetic components of the major immune pathways, except for the immune deficiency (Imd) pathway, are still retained in the body louse genome. Transcriptional profiling of representative genes involved in the humoral immune response, following bacterial challenge, revealed that both body and head lice, regardless of their developmental stages, exhibited an increased immune response to S. aureus but little to E. coli. Head lice, however, exhibited a significantly higher phagocytotic activity against E. coli than body lice, whereas the phagocytosis against S. aureus differed only slightly between body and head lice. These findings suggest that the greater immune response in head lice against E. coli is largely due to enhanced phagocytosis and not due to differences in the humoral immune response. The reduced phagocytotic activity in body lice could be responsible, in part, for their increased vector competence.

    Title Variation in Provider Identification of Obesity by Individual- and Neighborhood-level Characteristics Among an Insured Population.
    Date July 2011
    Journal Journal of Obesity
    Excerpt

    Objective. The purpose of this study was to examine whether neighborhood- and individual-level characteristics affect providers' likelihood of providing an obesity diagnosis code in their obese patients' claims. Methods. Logistic regressions were performed with obesity diagnosis code serving as the outcome variable and neighborhood characteristics and member characteristics serving as the independent variables (N = 16,151 obese plan members). Results. Only 7.7 percent of obese plan members had an obesity diagnosis code listed in their claims. Members living in neighborhoods with the largest proportions of Blacks were 29 percent less likely to receive an obesity diagnosis (P < .05). The odds of having an obesity diagnosis code were greater among members who were female, aged 44 or below, hypertensive, dyslipidemic, BMI >/= 35 kg/m(2), had a larger number of provider visits, or who lived in an urban area (all P < .05). Conclusions. Most health care providers do not include an obesity diagnosis code in their obese patients' claims. Rates of obesity identification were strongly related to individual characteristics and somewhat associated with neighborhood characteristics.

    Title Barriers to and Facilitators of Postpartum Follow-up Care in Women with Recent Gestational Diabetes Mellitus: a Qualitative Study.
    Date June 2011
    Journal Journal of Women's Health (2002)
    Excerpt

    Women with a history of gestational diabetes mellitus (GDM) have an increased risk of developing type 2 diabetes (T2DM) but often do not return for follow-up care. We explored barriers to and facilitators of postpartum follow-up care in women with recent GDM.

    Title Longitudinal Gait and Strength Changes Prior to and Following an Anterior Cruciate Ligament Rupture and Surgical Reconstruction: a Case Report.
    Date June 2011
    Journal The Journal of Orthopaedic and Sports Physical Therapy
    Excerpt

    Case report.

    Title Physical Activity Recommendations, Exercise Intensity, and Histological Severity of Nonalcoholic Fatty Liver Disease.
    Date April 2011
    Journal The American Journal of Gastroenterology
    Excerpt

    Factors that determine disease severity in nonalcoholic fatty liver disease (NAFLD) are unclear, but exercise is a recommended treatment. We evaluated the association between physical activity intensity and histological severity of NAFLD.

    Title Effect of Vitamin E or Metformin for Treatment of Nonalcoholic Fatty Liver Disease in Children and Adolescents: the Tonic Randomized Controlled Trial.
    Date April 2011
    Journal Jama : the Journal of the American Medical Association
    Excerpt

    Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in US children and adolescents and can present with advanced fibrosis or nonalcoholic steatohepatitis (NASH). No treatment has been established.

    Title Cardiac Pacing in Patients with a Cervical Spinal Cord Injury.
    Date March 2011
    Journal Spinal Cord
    Excerpt

    Retrospective medical record review.

    Title Temperature-dependent Rate Coefficients and Theoretical Calculations for the Oh+cl2o Reaction.
    Date March 2011
    Journal Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry
    Excerpt

    Rate coefficients k for the OH+Cl(2)O reaction are measured as a function of temperature (230-370 K) and pressure by using pulsed laser photolysis to produce OH radicals and laser-induced fluorescence to monitor their loss under pseudo-first-order conditions in OH. The reaction rate coefficient is found to be independent of pressure, within the precision of our measurements at 30-100 Torr (He) and 100 Torr (N(2)). The rate coefficients obtained at 100 Torr (He) showed a negative temperature dependence with a weak non-Arrhenius behavior. A room-temperature rate coefficient of k(1)(297 K)=(7.5±1.1)×10(-12) cm(3) molecule(-1) s(-1) is obtained, where the quoted uncertainties are 2σ and include estimated systematic errors. Theoretical methods are used to examine OH···OCl(2) and OH···ClOCl adduct formation and the potential-energy surfaces leading to the HOCl+ClO (1a) and Cl+HOOCl (1d) products in reaction (1) at the hybrid density functional UMPW1K/6-311++G(2df,p) level of theory. The OH···OCl(2) and OH···ClOCl adducts are found to have binding energies of about 0.2 kcal mol(-1). The reaction is calculated to proceed through weak pre-reactive complexes. Transition-state energies for channels (1a) and (1d) are calculated to be about 1.4 and about 3.3 kcal mol(-1) above the energy of the reactants. The results from the present study are compared with previously reported rate coefficients, and the interpretation of the possible non-Arrhenius behavior is discussed.

    Title Disparity in Physician Perception of Patients' Adherence to Medications by Obesity Status.
    Date March 2011
    Journal Obesity (silver Spring, Md.)
    Excerpt

    Physician perception of medication adherence may alter prescribing patterns. Perception of patients has been linked to readily observable factors, such as race and age. Obesity shares a similar stigma to these factors in society. We hypothesized that physicians would perceive patients with a higher BMI as nonadherent to medication. Data were collected from the baseline visit of a randomized clinical trial of patient-physician communication (240 patients and 40 physicians). Physician perception of patient medication adherence was measured on a Likert scale and dichotomized as fully adherent or not fully adherent. BMI was the predictor of interest. We performed Poisson regression analyses with robust variance estimates, adjusting for clustering of patients within physicians, to examine the association between BMI and physician perception of medication adherence. The mean (s.d.) BMI was 32.6 (7.7) kg/m(2). Forty-five percent of patients were perceived as nonadherent to medications by their physicians. Higher BMI was significantly and negatively associated with being perceived as adherent to medication (prevalence ratio (PrR) 0.76, 95% confidence interval (CI): 0.64-0.90; P = 0.002; per 10 kg/m(2) increase in BMI). BMI remained significantly and negatively associated with physician perception of medication adherence after adjustment for patient and physician characteristics (PrR 0.80, 95% CI: 0.66-0.96; P = 0.020). In this study, patients with higher BMI were less likely to be perceived as adherent to medications by their providers. Physician perception of medication adherence has been shown to affect prescribing patterns in other studies. More work is needed to understand how this perception may affect the care of patients with obesity.

    Title Enhanced Repellency of Binary Mixtures of Zanthoxylum Armatum Seed Oil, Vanillin, and Their Aerosols to Mosquitoes Under Laboratory and Field Conditions.
    Date March 2011
    Journal Journal of Medical Entomology
    Excerpt

    The repellency of Zanthoxylum armatum seed oil (ZA-SO), alone or in combination with vanillin (VA), its six major constituents, and another four major previously known Zanthoxylum piperitum fruit oil constituents, as well as aerosol products containing 5 or 10% ZA-SO and 5% VA, was evaluated against female Aedes aegypti in laboratory and field studies. Results were then compared with those of N,N-diethyl-3-methylbenzamide (DEET) as a standard. Hand in cage laboratory tests showed that 0.2, 0.1, and 0.05 mg/cm2 ZA-SO resulted in > 92% protection through 30-min postexposure and was not significantly different than 0.05 mg/cm2 DEET. Skin treated with linalool and limonene (from Z. armatum) provided > 80% repellency to female Ae. aegypti at 10-min exposure, whereas cuminaldehyde, citronellal, geranyl acetate, and cuminyl alcohol (from Zanthoxylum piperitum) provided > 90% protection during this same time period. Only cuminaldehyde and citronellal provided complete protection comparable to DEET at 10-min postexposure. After that time, repellency of all plant constituents to mosquitoes was considerably decreased (< approximately 65%). An increase in repellency and duration of effectiveness was produced by a binary 1:4 mixture of ZA-SO and VA (0.05:0.2 mg/cm2) that was significantly more effective than 0.05 mg/cm2 DEET through 90 min. In field tests, an aerosol formulation containing 5 or 10% ZA-SO plus 5% VA gave 100% repellency at 60-min postexposure. Although these formulations were equal to the level of protection afforded by 10% DEET, repellency to the binary ZA-SO aerosol formulations at 90 min was significantly less effective than DEET. However, mixtures formulated from ZA-SO and VA merit further study as potential repellents for protection of humans and domestic animals from biting and nuisance caused by mosquitoes.

    Title Effects of Metformin and Weight Loss on Serum Alanine Aminotransferase Activity in the Diabetes Prevention Program.
    Date February 2011
    Journal Obesity (silver Spring, Md.)
    Excerpt

    Nonalcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, and impaired glucose tolerance. We investigated whether metformin or changes in metabolic measurements (weight, fasting plasma glucose (FPG), or fasting insulin (FI)) improved serum alanine aminotransferase (ALT) activity, as a marker for NAFLD, in the Diabetes Prevention Program (DPP). From 1996 to 1999, 2,153 participants without marked elevations of serum ALT at baseline were randomized (1,081 to placebo, 1,072 to metformin) and treated for an average of 3.2 years. ALT increased during the first 2 years of the study, and was slightly but significantly lower in the participants randomized to metformin. In regression models adjusted for sex, baseline age, FPG, and FI, these differences remained significant, but disappeared after adjustment for weight, FPG, and FI changes at each examination. The 3-year cumulative incidence for development of abnormal ALT concentrations was not significantly different ((mean +/- s.e.) 21.4 +/- 1.4% and 24.6 +/- 1.4%, P = 0.11) in the metformin vs. placebo groups but was lower in individuals in both groups that lost more weight by the end of year 1 (metformin: 19.4 +/- 2.4% vs. 27.5 +/- 3.7%, for highest vs. lowest quartile of weight loss; placebo: 18.7 +/- 3.4% vs. 28.8 +/- 2.6%). Over 3 years of follow-up in persons at high risk for development of diabetes, serum ALT was consistently lower in those treated with metformin compared with placebo. This effect was mediated by weight loss, indicating that the effects of metformin therapy on ALT is via its effects on weight.

    Title Decreased Detoxification Genes and Genome Size Make the Human Body Louse an Efficient Model to Study Xenobiotic Metabolism.
    Date February 2011
    Journal Insect Molecular Biology
    Excerpt

    The human body louse, Pediculus humanus humanus, has one of the smallest insect genomes, containing ∼10 775 annotated genes. Annotation of detoxification [cytochrome P450 monooxygenase (P450), glutathione-S-transferase (GST), esterase (Est) and ATP-binding cassette transporter (ABC transporter)] genes revealed that they are dramatically reduced in P. h. humanus compared to other insects except for Apis mellifera. There are 37 P450, 13 GST and 17 Est genes present in P. h. humanus, approximately half the number found in Drosophila melanogaster and Anopheles gambiae. The number of putatively functional ABC transporter genes in P. h. humanus and Ap. mellifera are the same (36) but both have fewer than An. gambiae (44) or Dr. melanogaster (65). The reduction of detoxification genes in P. h. humanus may be a result of this louse's simple life history, in which it does not encounter a wide variety of xenobiotics. Neuronal component genes are highly conserved across different insect species as expected because of their critical function. Although reduced in number, P. h. humanus still retains at least a minimum repertoire of genes known to confer metabolic or toxicokinetic resistance to xenobiotics (eg Cyp3 clade P450s, Delta GSTs, B clade Ests and B/C subfamily ABC transporters), suggestive of its high potential for resistance development.

    Title Determination of Knockdown Resistance Allele Frequencies in Global Human Head Louse Populations Using the Serial Invasive Signal Amplification Reaction.
    Date January 2011
    Journal Pest Management Science
    Excerpt

    Pediculosis is the most prevalent parasitic infestation of humans. Resistance to pyrethrin- and pyrethroid-based pediculicides is due to knockdown (kdr)-type point mutations in the voltage-sensitive sodium channel alpha-subunit gene. Early detection of resistance is crucial for the selection of effective management strategies.

    Title Effect of a 12-month Intensive Lifestyle Intervention on Hepatic Steatosis in Adults with Type 2 Diabetes.
    Date January 2011
    Journal Diabetes Care
    Excerpt

    Weight loss through lifestyle changes is recommended for nonalcoholic fatty liver disease (NAFLD). However, its efficacy in patients with type 2 diabetes is unproven.

    Title Development of a Claims-based Risk Score to Identify Obese Individuals.
    Date December 2010
    Journal Population Health Management
    Excerpt

    Obesity is underdiagnosed, hampering system-based health promotion and research. Our objective was to develop and validate a claims-based risk model to identify obese persons using medical diagnosis and prescription records. We conducted a cross-sectional analysis of de-identified claims data from enrollees of 3 Blue Cross Blue Shield plans who completed a health risk assessment capturing height and weight. The final sample of 71,057 enrollees was randomly split into 2 subsamples for development and validation of the obesity risk model. Using the Johns Hopkins Adjusted Clinical Groups case-mix/predictive risk methodology, we categorized study members' diagnosis (ICD) codes. Logistic regression was used to determine which claims-based risk markers were associated with a body mass index (BMI) > or = 35 kg/m(2). The sensitivities of the scores > or =90(th) percentile to detect obesity were 26% to 33%, while the specificities were >90%. The areas under the receiver operator curve ranged from 0.67 to 0.73. In contrast, a diagnosis of obesity or an obesity medication alone had very poor sensitivity (10% and 1%, respectively); the obesity risk model identified an additional 22% of obese members. Varying the percentile cut-point from the 70(th) to the 99(th) percentile resulted in positive predictive values ranging from 15.5 to 59.2. An obesity risk score was highly specific for detecting a BMI > or = 35 kg/m(2) and substantially increased the detection of obese members beyond a provider-coded obesity diagnosis or medication claim. This model could be used for obesity care management and health promotion or for obesity-related research.

    Title Independent but Coordinated Trials: Insights from the Practice-based Opportunities for Weight Reduction Trials Collaborative Research Group.
    Date November 2010
    Journal Clinical Trials (london, England)
    Excerpt

    The National Heart, Lung, and Blood Institute (NHLBI) funded three institutions to conduct effectiveness trials of weight loss interventions in primary care settings. Unlike traditional multi-center clinical trials, each study was established as an independent trial with a distinct protocol. Still, efforts were made to coordinate and standardize several aspects of the trials. The three trials formed a collaborative group, the 'Practice-based Opportunities for Weight Reduction (POWER) Trials Collaborative Research Group.'

    Title Pyrethroid Pediculicide Resistance of Head Lice in Canada Evaluated by Serial Invasive Signal Amplification Reaction.
    Date October 2010
    Journal Journal of Cutaneous Medicine and Surgery
    Excerpt

    Most people in the United States and Canada with pediculosis will be treated with neurotoxic pediculicides containing pyrethrins or pyrethroids. Their widespread use led to significant resistance reported from various countries. Although treatment failures are frequently observed in Canada, the resistance frequency to pyrethroid pediculicide of human head lice (Pediculus humanus capitis) has not been determined.

    Title A Point Mutation in a Glutamate-gated Chloride Channel Confers Abamectin Resistance in the Two-spotted Spider Mite, Tetranychus Urticae Koch.
    Date October 2010
    Journal Insect Molecular Biology
    Excerpt

    The molecular mechanisms and genetics of abamectin resistance mediated by target site insensitivity in the two-spotted spider mite, Tetranychus urticae, were investigated by comparing two isogenic abamectin-susceptible (AbaS) and abamectin-resistant (AbaR) strains. Cloning and sequencing of full-length cDNA fragments of gamma-amino butyric acid (GABA)-gated chloride channel genes revealed no polymorphisms between the two strains. However, sequence comparison of the full-length cDNA fragment of a T. urticae glutamate-gated chloride channel gene (TuGluCl) identified a G323D point mutation as being tentatively related with abamectin resistance. In individual F(2) progenies obtained by backcrossing, the G323D genotype was confirmed to correlate with abamectin resistance. Bioassays using progeny from reciprocal crossings revealed that the abamectin resistance trait resulting from TuGluCl insensitivity is incompletely recessive.

    Title Clinical, Laboratory and Histological Associations in Adults with Nonalcoholic Fatty Liver Disease.
    Date October 2010
    Journal Hepatology (baltimore, Md.)
    Excerpt

    The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) was formed to conduct multicenter studies on the etiology, contributing factors, natural history, and treatment of nonalcoholic steatohepatitis (NASH). The aim of this study was to determine the associations of readily available demographic, clinical, and laboratory variables with the diagnosis of NASH and its key histological features, and determine the ability of these variables to predict the severity of nonalcoholic fatty liver disease (NAFLD). A total of 1266 adults were enrolled in NASH CRN studies between October 2004 and February 2008, of whom 1101 had available liver histology. The median age was 50 years; 82% were white and 12% Hispanic. The median body mass index was 33 kg/m(2); 49% had hypertension and 31% had type 2 diabetes. On liver biopsy, 57% were judged to have definite NASH and 31% bridging fibrosis or cirrhosis. Using data from the 698 patients with liver biopsies within 6 months of clinical data, patients with definite NASH were more likely to be female and have diabetes, higher levels of aspartate and alanine aminotransferases, alkaline phosphatase, gamma glutamyl transpeptidase, and homeostasis model assessment of insulin resistance (HOMA-IR). Progressive models for predicting histological diagnoses performed modestly for predicting steatohepatitis or ballooning (area under receiver operating characteristic curves [AUROC] ranged from 0.70-0.79), and better for advanced fibrosis (AUROC 0.73-0.85). CONCLUSION: Readily available clinical and laboratory variables can predict advanced fibrosis in adults with NAFLD, but additional information is needed to reliably predict the presence and severity of NASH. Prospective studies of this well-characterized population and associated tissue bank samples offer a unique opportunity to better understand the cause and natural history of NAFLD and develop more precise means for noninvasive diagnosis.

    Title Reduced Incidence of Gestational Diabetes with Bariatric Surgery.
    Date September 2010
    Journal Journal of the American College of Surgeons
    Excerpt

    Obesity is a risk factor for gestational diabetes mellitus (GDM), and bariatric surgery is an effective treatment for obesity. Our objective was to determine the association of bariatric surgery with the incidence of GDM and related complications.

    Title Establishment of Quantitative Sequencing and Filter Contact Vial Bioassay for Monitoring Pyrethroid Resistance in the Common Bed Bug, Cimex Lectularius.
    Date September 2010
    Journal Journal of Medical Entomology
    Excerpt

    Two point mutations (V419L and L925I) in the voltage-sensitive sodium channel alpha-subunit gene have been identified in deltamethrin-resistant bed bugs. A quantitative sequencing (QS) protocol was developed to establish a population-based genotyping method as a molecular resistance-monitoring tool based on the frequency of the two mutations. The nucleotide signal ratio at each mutation site was generated from sequencing chromatograms and plotted against the corresponding resistance allele frequency. Frequency prediction equations were generated from the plots by linear regression, and the signal ratios were shown to highly correlate with resistance allele frequencies (r2 > 0.9928). As determined by QS, neither mutation was found in a bed bug population collected in 1993. Populations collected in recent years (2007-2009), however, exhibited completely or nearly saturating L925I mutation frequencies and highly variable frequencies of the V419L mutation. In addition to QS, the filter contact vial bioassay (FCVB) method was established and used to determine the baseline susceptibility and resistance of bed bugs to deltamethrin and lambda-cyhalothrin. A pyrethroid-resistant strain showed >9,375- and 6,990-fold resistance to deltamethrin and lambda-cyhalothrin, respectively. Resistance allele frequencies in different bed bug populations predicted by QS correlated well with the FCVB results, confirming the roles of the two mutations in pyrethroid resistance. Taken together, employment of QS in conjunction with FCVB should greatly facilitate the detection and monitoring of pyrethroid-resistant bed bugs in the field. The advantages of FCVB as an on-site resistance-monitoring tool are discussed.

    Title Genome Sequences of the Human Body Louse and Its Primary Endosymbiont Provide Insights into the Permanent Parasitic Lifestyle.
    Date August 2010
    Journal Proceedings of the National Academy of Sciences of the United States of America
    Excerpt

    As an obligatory parasite of humans, the body louse (Pediculus humanus humanus) is an important vector for human diseases, including epidemic typhus, relapsing fever, and trench fever. Here, we present genome sequences of the body louse and its primary bacterial endosymbiont Candidatus Riesia pediculicola. The body louse has the smallest known insect genome, spanning 108 Mb. Despite its status as an obligate parasite, it retains a remarkably complete basal insect repertoire of 10,773 protein-coding genes and 57 microRNAs. Representing hemimetabolous insects, the genome of the body louse thus provides a reference for studies of holometabolous insects. Compared with other insect genomes, the body louse genome contains significantly fewer genes associated with environmental sensing and response, including odorant and gustatory receptors and detoxifying enzymes. The unique architecture of the 18 minicircular mitochondrial chromosomes of the body louse may be linked to the loss of the gene encoding the mitochondrial single-stranded DNA binding protein. The genome of the obligatory louse endosymbiont Candidatus Riesia pediculicola encodes less than 600 genes on a short, linear chromosome and a circular plasmid. The plasmid harbors a unique arrangement of genes required for the synthesis of pantothenate, an essential vitamin deficient in the louse diet. The human body louse, its primary endosymbiont, and the bacterial pathogens that it vectors all possess genomes reduced in size compared with their free-living close relatives. Thus, the body louse genome project offers unique information and tools to use in advancing understanding of coevolution among vectors, symbionts, and pathogens.

    Title Physician Respect for Patients with Obesity.
    Date August 2010
    Journal Journal of General Internal Medicine
    Excerpt

    Obesity stigma is common in our society, and a general stigma towards obesity has also been documented in physicians. We hypothesized that physician respect for patients would be lower in patients with higher body mass index (BMI).

    Title Late Repair of Abductor Avulsion After the Transgluteal Approach for Hip Arthroplasty.
    Date August 2010
    Journal The Journal of Arthroplasty
    Excerpt

    The abductor release sometimes does not heal after a transgluteal approach for hip arthroplasty. Factors influencing the success of subsequent repair are unclear. We used magnetic resonance imaging (MRI) to compare the condition of the gluteus medius with clinical outcome after late repair of abductor dehiscence in 12 total hip patients. Evaluation included a pain rating, gait evaluation, Trendelenburg test, strength grading, and Harris Hip Score. Most had both prerepair and postrepair MRI studies to assess the repair and to grade abductor muscle fatty degeneration. Two repairs without MRI were explored surgically. Although average pain, limp, and strength scores improved significantly, rerupture occurred in 4 subjects and fatty degeneration in the gluteus medius did not improve, even with intact repair. Nine patients were satisfied; 7 of these had an intact repair. Magnetic resonance imaging and operative observations suggest that chronic degeneration in the abductor mechanism is the major impediment to successful repair.

    Title Extensive Gene Duplication of Acetylcholinesterase Associated with Organophosphate Resistance in the Two-spotted Spider Mite.
    Date August 2010
    Journal Insect Molecular Biology
    Excerpt

    Monocrotophos-resistant two-spotted spider mites (TSSMs), Tetranychus urticae, are known to possess three mutations on the acetylcholinesterase (AChE) gene (Tuace) that are involved in target site insensitivity. Cross-strain comparison of three strains (highly resistant AD, moderately resistant PyriF and susceptible UD strains) revealed that resistant strains have relatively more Tuace copies than the UD strain and that the levels of transcript were directly proportional to copy numbers. AChEs from the AD and PyriF strains had similar V(max) values to those of AChE from the UD strain but increased K(m) and reduced k(cat) constants, suggesting that the mutated, resistant form of AChE may carry a fitness cost. Relative copy numbers of Tuace in field populations varied from 2.4 to 6.1, correlating well with their levels of resistance (r(2)= 0.895). These results are suggestive of the involvement of Tuace gene duplication in resistance. Thus, monocrotophos resistance in TSSMs appears to have evolved through a combination of mutation accumulation and extensive gene duplication.

    Title A Near Infrared Instrument to Monitor Relative Hemoglobin Concentrations of Human Bone Tissue in Vitro and in Vivo.
    Date July 2010
    Journal The Review of Scientific Instruments
    Excerpt

    A continuous wave near infrared instrument has been developed to monitor in vivo changes in the hemoglobin concentration of the trabecular compartment of human bone. The transmitter uses only two laser diodes of wavelengths 685 and 830 nm, and the receiver uses a single silicon photodiode operating in the photovoltaic mode. The functioning of the instrument and the depth of penetration of the near infrared signals was determined in vitro using tissue-equivalent phantoms. The instrument achieves a depth of penetration of approximately 2 cm for an optode separation of 4 cm and, therefore, has the capacity to interrogate the trabecular compartment of human bone. The functioning of the instrument was tested in vivo to evaluate the relative oxy-hemoglobin (HbO(2)) and deoxy-hemoglobin (Hb) concentrations of the proximal tibial bone of apparently healthy, normal weight, adult subjects in response to a 3 min on, 5 min off, vascular occlusion protocol. The traces of the relative Hb and HbO(2) concentrations obtained were reproducible in controlled conditions. The instrument is relatively simple and flexible, and offers an inexpensive platform for further studies to obtain normative data for healthy cohorts, and to evaluate disease-specific performance characteristics for cohorts with vasculopathies of bone.

    Title Efficacy of Spray Formulations Containing Binary Mixtures of Clove and Eucalyptus Oils Against Susceptible and Pyrethroid/ Malathion-resistant Head Lice (anoplura: Pediculidae).
    Date July 2010
    Journal Journal of Medical Entomology
    Excerpt

    The control efficacy of clove, Eugenia caryophyllata, and eucalyptus, Eucalyptus globulus, essential oils and 15 formulations containing these essential oils alone (8, 12, and 15% sprays) and their binary mixtures (7:3, 5:5, and 3:7 by weight) against adult females of insecticide-susceptible KR-HL and dual malathion- and permethrin-resistant BR-HL strains of head louse, Pediculus humanus capitis (De Geer), was examined by using contact plus fumigant and human hair wig (placed over the head of mannequin) mortality bioassays. In contact plus fumigant mortality bioassay, essential oils from eucalyptus (0.225 mg/cm2) and clove (1.149 mg/cm2) were less effective than either d-phenothrin (0.0029 mg/cm2) or pyrethrum (0.0025 mg/cm2) based on 6-h median lethal concentration values. However, the efficacies of eucalyptus and clove oils were almost identical against females fromn both strains, despite high levels of resistance of the BR-HL females to d-phenothrin (resistance ratio, 667) and pyrethrum (resistance ratio, 754). In human hair wig mortality bioassay, eucalyptus oil spray treatment gave better control efficacy than either spray treatment with clove oil alone or their binary mixtures. Thus, eucalyptus applied as 8% sprays (15 or 20 ml) appears to provide effective protection against pediculosis even to insecticide-resistant head louse populations. Once the safety issues resolved, covering the treated hair and scalp with bath shower cap or hat would ensure the fumigant action of the essential oil.

    Title Specific Cell-cell Contact Serves As the Developmental Signal to Deactivate Discoidin I Gene Expression in Dictyostelium Discoideum.
    Date June 2010
    Journal Proceedings of the National Academy of Sciences of the United States of America
    Excerpt

    Specific cell-cell contact is a major regulatory signal controlling cell differentiation in Dictyostelium discoideum, causing dramatic changes in the developmental program of gene expression. In this report, we focus on the relationships between specific cell-cell contact and the activity of the genes for discoidin I, an endogenous lectin that has been implicated in the cell-cell cohesion process. By performing quantitative RNA dot-hybridization assays and RNA gel blot-hybridization analyses, using as a probe a recombinant plasmid containing a discoidin I cDNA insert, we have measured changes in discoiding I mRNA levels during normal development and in response to specific manipulations of the state of cellular aggregation. Our major findings are as follows. (i) During normal development on filters, there is a close temporal correspondence between the establishment of specific cell-cell contacts and the decline in discoidin I mRNA levels. By the tight-aggregate stage, discoidin I mRNA is barely detectable. (ii) When tight aggregates are disaggregated and the cells are maintained in the disaggregated state, there is a dramatic rise in discoidin I mRNA content. (iii) When cells are developed in suspension (conditions that interfere with the establishment of tight cell-cell contacts), discoidin I mRNA accumulates to abnormally high levels, and these persist well after the levels in filter-developed cells have declined. Taken together, these results strongly suggest that cell-cell contact is the normal developmental signal to deactivate discoidin I gene expression; thus, a contact-deactivated gene for which a recombinant DNA probe is available has now been identified. Furthermore, we demonstrate that exogenous cAMP almost completely blocks the disaggregation-induced reactivation of discoidin I gene expression. Possible mechanistic relationships between specific cell-cell contact, intracellular cAMP levels, and developmental gene expression are discussed.

    Title Semicontinuous Pm2.5 and Pm10 Mass and Composition Measurements in Lindon, Utah, During Winter 2007.
    Date May 2010
    Journal Journal of the Air & Waste Management Association (1995)
    Excerpt

    The U.S. Environmental Protection Agency is promoting the development and application of sampling methods for the semicontinuous determination of fine particulate matter (PM2.5, particles with an aerodynamic diameter <2.5 microm) mass and chemical composition. Data obtained with these methods will significantly improve the understanding of the primary sources, chemical conversion processes, and meteorological atmospheric processes that lead to observed PM2.5 concentrations and will aid in the understanding of the etiology of PM2.5-related health effects. During January and February 2007, several semicontinuous particulate matter (PM) monitoring systems were compared at the Utah State Lindon Air Quality Sampling site. Semicontinuous monitors included instruments to measure total PM2.5 mass (filter dynamic measurement system [FDMS] tapered element oscillating microbalance [TEOM], GRIMM), nonvolatile PM2.5 mass (TEOM), sulfate and nitrate (two PM2.5 and one PM10 [PM with an aerodynamic diameter <10 microm] ion-chromatographic-based samplers), and black carbon (aethalometer). PM10 semicontinuous mass measurements were made with GRIMM and TEOM instruments. These measurements were all made on a 1-hr average basis. Source apportionment analysis indicated that sources impacting the site were mainly urban sources and included mobile sources (gasoline and diesel) and residential burning of wood, with some elevated concentrations because of the effect of winter inversions. The FDMS TEOM and GRIMM instruments were in good agreement, but TEOM monitor measurements were low because of the presence of significant semi-volatile material. Semi-volatile mass was present dominantly in the PM2.5 mass.

    Title Repeatability of Subjective Evaluation of Lameness in Horses.
    Date April 2010
    Journal Equine Veterinary Journal
    Excerpt

    Previous studies have suggested that agreement between equine veterinarians subjectively evaluating lameness in horses is low. These studies were limited to small numbers of horses, evaluating movement on the treadmill or to evaluating previously-recorded videotape.

    Title Prompt Reduction in Use of Medications for Comorbid Conditions After Bariatric Surgery.
    Date April 2010
    Journal Obesity Surgery
    Excerpt

    Bariatric surgery leads to weight loss, but it is unclear whether surgery reduces conditions associated with obesity. We explored this by assessing the change in use of medications to treat diabetes mellitus, hypertension, and hyperlipidemia in the year following surgery.

    Title Impact of Bariatric Surgery on Hypertensive Disorders in Pregnancy: Retrospective Analysis of Insurance Claims Data.
    Date April 2010
    Journal Bmj (clinical Research Ed.)
    Excerpt

    To determine whether women who had a delivery after bariatric surgery have lower rates of hypertensive disorders in pregnancy compared with women who had a delivery before bariatric surgery.

    Title Trends in and Patterns of Obesity Reduction Medication Use in an Insured Cohort.
    Date March 2010
    Journal Obesity (silver Spring, Md.)
    Excerpt

    Several prescription medications are approved to treat obesity, yet little is known about their use in the United States. Our objective was to describe recent trends and patterns of obesity reduction medication use in an insured US population. From among ~4.2 million persons enrolled in two Blue Cross and Blue Shield plans, we obtained all medical and pharmacy claims for 86,804 persons who took an obesity reduction medication anytime during 2002-2005. Overall, obesity reduction medication use decreased significantly over time from 1% in 2002 to 0.7% in 2005 (P for trend <0.001), which was most notable for the newer medications (orlistat and sibutramine). Few (range: 11-18%) used these medications longer than 3 months regardless of whether they were Federal Drug Administration (FDA)-approved for long-term use or not. More than half (57%) of obesity reduction medication users also took narcotics and 38% took antidepressants. Few sympathomimetic users had potential serious contraindications prior to medication initiation, including cardiovascular diseases (2.4%), schizophrenia (2.5%), and age >65 (1.2%). Despite the high prevalence of obesity, obesity reduction medication use was low and decreased significantly from 2002 through 2005. Prescribers of these agents should be aware of approved durations, potential contraindications, and consider screening for depression and substance abuse.

    Title Evidence for a Separate Mechanism of Toxicity for the Type I and the Type Ii Pyrethroid Insecticides.
    Date March 2010
    Journal Neurotoxicology
    Excerpt

    Neurotoxicity and mechanistic data were collected for six alpha-cyano pyrethroids (beta-cyfluthrin, cypermethrin, deltamethrin, esfenvalerate, fenpropathrin and lambda-cyhalothrin) and up to six non-cyano containing pyrethroids (bifenthrin, S-bioallethrin [or allethrin], permethrin, pyrethrins, resmethrin [or its cis-isomer, cismethrin] and tefluthrin under standard conditions. Factor analysis and multivariate dissimilarity analysis were employed to evaluate four independent data sets comprised of (1) fifty-six behavioral and physiological parameters from an acute neurotoxicity functional observatory battery (FOB), (2) eight electrophysiological parameters from voltage clamp experiments conducted on the Na(v)1.8 sodium channel expressed in Xenopus oocytes, (3) indices of efficacy, potency and binding calculated for calcium ion influx across neuronal membranes, membrane depolarization and glutamate released from rat brain synaptosomes and (4) changes in chloride channel open state probability using a patch voltage clamp technique for membranes isolated from mouse neuroblastoma cells. The pyrethroids segregated into Type I (T--syndrome-tremors) and Type II (CS syndrome--choreoathetosis with salivation) groups based on FOB data. Of the alpha-cyano pyrethroids, deltamethrin, lambda-cyhalothrin, cyfluthrin and cypermethrin arrayed themselves strongly in a dose-dependent manner along two factors that characterize the CS syndrome. Esfenvalerate and fenpropathrin displayed weaker response profiles compared to the non-cyano pyrethroids. Visual clustering on multidimensional scaling (MDS) maps based upon sodium ion channel and calcium influx and glutamate release dissimilarities gave similar groupings. The non-cyano containing pyrethroids were arrayed in a dose-dependent manner along two different factors that characterize the T-syndrome. Bifenthrin was an outlier when MDS maps of the non-cyano pyrethroids were based on sodium ion channel characteristics and permethrin was an outlier when the MDS maps were based on calcium influx/glutamate release potency. Four of six alpha-cyano pyrethroids (lambda-cyfluthrin, cypermethrin, deltamethrin and fenpropathrin) reduced open chloride channel probability. The R-isomers of lambda-l-cyhalothrin reduced open channel probability whereas the S-isomers, antagonized the action of the R-isomers. None of the non-cyano pyrethroids reduced open channel probability, except bioallethrin, which gave a weak response. Overall, based upon neurotoxicity data and the effect of pyrethroids on sodium, calcium and chloride ion channels, it is proposed that bioallethrin, cismethrin, tefluthrin, bifenthrin and permethrin belong to one common mechanism group and deltamethrin, lambda-cyhalothrin, cyfluthrin and cypermethrin belong to a second. Fenpropathrin and esfenvalerate occupy an intermediate position between these two groups.

    Title Acute Success of Cryoablation of Left-sided Accessory Pathways: a Single Institution Study.
    Date October 2009
    Journal Journal of Cardiovascular Electrophysiology
    Excerpt

    To compare the acute success and recurrence rate of cryoablation for left-sided accessory pathways (AP) with controls who underwent radiofrequency ablation (RFA) at the same institution.

    Title Genomic and Bioinformatics Analyses of Hadv-14p, Reference Strain of a Re-emerging Respiratory Pathogen and Analysis of B1/b2.
    Date July 2009
    Journal Virus Research
    Excerpt

    Unlike other human adenovirus (HAdV) species, B is divided into subspecies B1 and B2. Originally this was partly based on restriction enzyme (RE) analysis. B1 members, except HAdV-50, are commonly associated with respiratory diseases while B2 members are rarely associated with reported respiratory diseases. Recently two members of B2 have been identified in outbreaks of acute respiratory disease (ARD). One, HAdV-14, has re-emerged after an apparent 52-year absence. Genomic analysis and bioinformatics data are reported for HAdV-14 prototype for use as a reference and to understand and counter its re-emergence. The data complement and extend the original criteria for subspecies designation, unique amongst the adenoviruses, and highlight differences between B1 and B2, representing the first comprehensive analysis of this division. These data also provide finer granularity into the pathoepidemiology of the HAdVs. Whole genome analysis uncovers heterogeneous identity structures of the hexon and fiber genes amongst the HAdV-14 and the B1/B2 subspecies, which may be important in prescient vaccine development. Analysis of cell surface proteins provides insight into HAdV-14 tropism, accounting for its role as a respiratory pathogen. This HAdV-14 prototype genome is also a reference for applications of B2 adenoviruses as vectors for vaccine development and gene therapy.

    Title Effect of Gastric Bypass Surgery on Kidney Stone Disease.
    Date June 2009
    Journal The Journal of Urology
    Excerpt

    Recent studies have demonstrated that mineral and electrolyte abnormalities develop in patients who undergo bariatric surgery. While it is known that these abnormalities are a risk factor for urolithiasis, the prevalence of stone disease after bariatric surgery is unknown. We evaluated the likelihood of being diagnosed with or treated for an upper urinary tract calculus following Roux-en-Y gastric bypass surgery.

    Title Ovicidal and Adulticidal Activities of Origanum Majorana Essential Oil Constituents Against Insecticide-susceptible and Pyrethroid/malathion-resistant Pediculus Humanus Capitis (anoplura: Pediculidae).
    Date May 2009
    Journal Journal of Agricultural and Food Chemistry
    Excerpt

    The toxicity of essential oil constituents from marjoram, Origanum majorana, to eggs and adult females of the susceptible KR-HL and dual malathion- and permethrin-resistant BR-HL strains of human head louse, Pediculus humanus capitis, was examined using contact + fumigant mortality bioassay. Results were compared with those following treatment with two pyrethroid pediculicides, d-phenothrin or pyrethrum. As judged by the lethal time to 50% mortality (LT(50)) values at the exposure rate of 0.25 mg/cm(2), 1,8-cineole (14.1 min) was the most toxic compound, followed by linalool (15.4 min) to KR-HL females. These compounds were faster acting than either d-phenothrin (24.1 min) or pyrethrum (33.4 min). Based on the lethal concentration causing 50% mortality (LC(50)) values, (-)-camphor (0.022 mg/cm(2)) was the most toxic compound, followed by linalool (0.035 mg/cm(2)), (-)-terpinen-4-ol (0.040 mg/cm(2)), alpha-terpineol (0.045 mg/cm(2)), and 1,8-cineole (0.068 mg/cm(2)) against KR-HL females. These monoterpenoids were less toxic than either d-phenothrin (LC(50), 0.0015 mg/cm(2)) or pyrethrum (0.0013 mg/cm(2)). However, the toxicities of these monoterpenoids were almost identical against females from either of the two strains, even though the BR-HL females exhibited high levels of resistance to d-phenothrin [resistance ratio (RR), 667] and pyrethrum (RR, 754). After a 24 h exposure to linalool, BR-HL egg hatch was inhibited 100 and 84% at 0.25 or 0.125 mg/cm(2), respectively, while (-)-terpinen-4-ol caused 94 and 69% inhibition of egg hatch at 0.25 and 0.125 mg/cm(2). alpha-Terpineol caused 88 and 76% inhibition of egg hatch at 0.5 and 0.25 mg/cm(2), respectively. Thus, certain monoterpenoids from O. majorana essential oil, particularly linalool, (-)-terpinen-4-ol and alpha-terpineol, merit further study as potential pediculicides and ovicides for the control of insecticide-resistant P. h. capitis populations as fumigants with contact action.

    Title Obstructive Sleep Apnea, Insulin Resistance, and Steatohepatitis in Severe Obesity.
    Date March 2009
    Journal American Journal of Respiratory and Critical Care Medicine
    Excerpt

    Obstructive sleep apnea is associated with insulin resistance and liver injury. It is unknown whether apnea contributes to insulin resistance and steatohepatitis in severe obesity.

    Title The Epidemiology of Nonalcoholic Fatty Liver Disease: a Global Perspective.
    Date January 2009
    Journal Seminars in Liver Disease
    Excerpt

    Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized cause of liver disease in the United States and worldwide. With obesity being an important risk factor universally, NAFLD is now receiving greater attention and is regarded as a public health issue. In addition, as a result of an aging population and the improving control of other major causes of chronic liver disease, such as hepatitis C and hepatitis B, the burden of NAFLD is expected to increase in years to come. Prevalence estimates of this disease vary widely across populations because of differences in methods for diagnosis and/or definition. New strategies for the prevention, diagnosis, and management will be required to alter the course of this disease.

    Title Biochemical and Molecular Analysis of Deltamethrin Resistance in the Common Bed Bug (hemiptera: Cimicidae).
    Date January 2009
    Journal Journal of Medical Entomology
    Excerpt

    This study establishes deltamethrin resistance in a common bed bug, Cimex lectularius L., population collected from New York City (NY-BB). The NY-BB population was 264-fold more resistant to 1% deltamethrin in contact bioassay compared with an insecticide-susceptible population collected in Florida (FL-BB). General esterase, glutathione S-transferase, and 7-ethoxycoumarin O-deethylase activities of NY-BB were not statistically different from those of FL-BB. cDNA fragments that encoded the open reading frame of voltage-sensitive sodium channel alpha-subunit genes from the FL-BB and NY-BB populations, respectively, were obtained by homology probing polymerase chain reaction (PCR) and sequenced. Sequence alignment of the internal and 5' and 3' rapid amplification of cDNA ends (RACE) fragments generated a 6500-bp cDNA sequence contig, which was composed of a 6084-bp open reading frame (ORF) encoding 2027 amino acid residues and 186-bp 5' and 230-bp 3' untranslated regions (5' and 3' UTRs, respectively). Sequence comparisons of the open reading frames of the alpha-subunit genes identified two point mutations (V419L and L925I) that were presented only in the NY-BB population. L925I, located the intracellular loop between IIS4 and IIS5, has been previously found in a highly pyrethroid-resistant populations of whitefly (Bemisia tabaci). V419L, located in the IS6 transmembrane segment, is a novel mutation. A Val to Met mutation at the corresponding position of the bed bug V419, however, has been identified in the tobacco budworm as a kdr-type mutation. This evidence suggests that the two mutations are likely the major resistance-causing mutations in the deltamethrin-resistant NY-BB through a knockdown-type nerve insensitivity mechanism.

    Title Link Between Doc in Near Surface Peat and Stream Water in an Upland Catchment.
    Date December 2008
    Journal The Science of the Total Environment
    Excerpt

    Hydrologic transport of dissolved organic carbon (DOC) from peat soils may differ to organo-mineral soils in how they responded to changes in flow, because of differences in soil profile and hydrology. In well-drained organo-mineral soils, low flow is through the lower mineral layer where DOC is absorbed and high flow is through the upper organic layer where DOC is produced. DOC concentrations in streams draining organo-mineral soils typically increase with flow. In saturated peat soils, both high and low flows are through an organic layer where DOC is produced. Therefore, DOC in stream water draining peat may not increase in response to changes in flow as there is no switch in flow path between a mineral and organic layer. To verify this, we conducted a high-resolution monitoring study of soil and stream water at an upland peat catchment in northern England. Our data showed a strong positive correlation between DOC concentrations at -1 and -5 cm depth and stream water, and weaker correlations between concentrations at -20 to -50 cm depth and stream water. Although near surface organic material appears to be the key source of stream water DOC in both peat and organo-mineral soils, we observed a negative correlation between stream flow and DOC concentrations instead of a positive correlation as DOC released from organic layers during low and high flow was diluted by rainfall. The differences in DOC transport processes between peat and organo-mineral soils have different implications for our understanding of long-term changes in DOC exports. While increased rainfall may cause an increase in DOC flux from peat due to an increase in water volume, it may cause a decrease in concentrations. This response is contrary to expected changes in DOC exports from organo-mineral soils, where increase rainfall is likely to result in an increase in flux and concentration.

    Title Buffering of Recovery from Acidification by Organic Acids.
    Date December 2008
    Journal The Science of the Total Environment
    Excerpt

    In the United Kingdom, as in other regions of Europe and North America, recent decreases in surface water sulphate concentrations, due to reduced sulphur emissions, have coincided with marked increases in dissolved organic carbon (DOC) concentrations. Since many of the compounds comprising DOC are acidic, the resulting increases in organic acidity may have the potential to offset the benefits of a decrease in mineral (sulphate) acidity. To test this, we used a triprotic model of organic acid dissociation to estimate the proportional organic acid buffering of reduced mineral acidity as measured in the 22 lakes and streams monitored by the UK Acid Waters Monitoring Network. For an average non-marine sulphate decrease of 30 mueq l(-1) over 15 years from 1988-2003, we estimate that around 28% was counterbalanced by rising strong organic acids, 20% by rising alkalinity (partly attributable to an increase in weak organic acids), 11% by falling inorganic aluminium and 41% by falling non-marine base cations. The situation is complicated by a concurrent decrease in marine ion concentrations, and the impact this may have had on both DOC and acidity, but results clearly demonstrate that organic acid increases have substantially limited the amount of recovery from acidification (in terms of rising alkalinity and falling aluminium) that have resulted from reducing sulphur emissions. The consistency and magnitude of sulphate and organic acid changes are consistent with a causal link between the two, possibly due to the effects of changing acidity, ionic strength and aluminium concentrations on organic matter solubility. If this is the case, then organic acids can be considered effective but partial buffers to acidity change in organic soils, and this mechanism needs to be considered in assessing and modelling recovery from acidification, and in defining realistic reference conditions. However, large spatial variations in the relative magnitude of organic acid and sulphate changes, notably for low-deposition sites in northwestern areas where organic acid increases apparently exceed non-marine sulphate decreases, suggest that additional factors, such as changes in sea-salt deposition and climatic factors, may be required to explain the full magnitude of DOC increases in UK surface waters.

    Title The Effect of a Probiotic on Hepatic Steatosis.
    Date December 2008
    Journal Journal of Clinical Gastroenterology
    Title Neurotoxic Implications of the Agonistic Action of Cs-syndrome Pyrethroids on the N-type Ca(v)2.2 Calcium Channel.
    Date December 2008
    Journal Pest Management Science
    Excerpt

    Cismethrin (T-syndrome) and deltamethrin (CS-syndrome) pyrethroids have been previously shown to increase membrane depolarization and calcium influx, but only deltamethrin increased Ca(2+)-dependent neurotransmitter release from rat brain synaptosomes. Deltamethrin's action was blocked by omega-conotoxin GVIA, delineating a separate action at N-type Ca(v)2.2 channels that is consistent with the in vivo release of neurotransmitter. It is hypothesized that other CS-syndrome pyrethroids will elicit similar actions at presynaptic nerve terminals.

    Title Determination of Permethrin Resistance Allele Frequency of Human Head Louse Populations by Quantitative Sequencing.
    Date November 2008
    Journal Journal of Medical Entomology
    Excerpt

    A quantitative sequencing (QS) protocol that detects the frequencies of sodium channel mutations (M815I, T917I, and L920F) responsible for knockdown resistance in permethrin-resistant head lice (Pediculus humanus capitis De Geer) was tested as a population genotyping method for use as a preliminary resistance monitoring tool. Genomic DNA fragments of the sodium channel a-subunit gene that encompass the three mutation sites were polymerase chain reaction (PCR)-1 amplified from individual head lice with either resistant or susceptible genotypes, and combined in various ratios to generate standard DNA template mixtures for QS. After sequencing, the signal ratios between resistant and susceptible nucleotides were calculated and plotted against the corresponding resistance allele frequencies. Quadratic regression coefficients of the plots were close to 1, demonstrating that the signal ratios are highly correlated with the resistance allele frequencies. Resistance allele frequencies predicted by QS, using either "pooled DNA" (DNA extracted from individual louse specimens and pooled) or "pooled specimen DNA" (DNA simultaneously extracted from multiple louse specimens), agreed well with those determined by individual sequencing, confirming the reliability and accuracy of QS as a population genotyping method and validating our approach of using the pooled specimen DNA as the DNA template for QS. Our protocol for QS was determined to be highly reliable for the prediction of resistance allele frequencies higher than approximately 7.4% at the 95% confidence level. According to the resistance allele frequencies determined by QS, pyrethroid resistance varies substantially among different geographical regions, emphasizing the importance of early resistance detection and proper management strategies.

    Title Cerebral Oximetry Does Not Correlate with Electroencephalography and Somatosensory Evoked Potentials in Determining the Need for Shunting During Carotid Endarterectomy.
    Date September 2008
    Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
    Excerpt

    OBJECTIVE: Several reports in the literature have described the value of regional cerebral oximetry (rSO(2)) as a neuromonitoring device during carotid endarterectomy (CEA). The use of rSO(2) is enticing because it is simpler and less expensive than other neuromonitoring modalities. This study was performed to compare the efficacy of rSO(2) with electroencephalography (EEG) and median nerve somatosensory evoked potentials (SSEP) in determining when to place a shunt during CEA. METHODS: From October 2000 to June 2006, 323 CEAs were performed under general anesthesia by six surgeons. Shunting was done selectively on the basis of EEG and SSEP monitoring under the auspices of an intraoperative neurophysiologist. All patients were retrospectively reviewed to see if significant discrepancies existed between EEG/SSEP and rSO(2). RESULTS: Twenty-four patients (7.4%) showed significant discrepancies. Sixteen patients showed no significant EEG/SSEP changes, but profound changes occurred in rSO(2), and no shunt was placed. In seven patients there was no change in rSO(2) but a profound change occurred in EEG/SSEP, and shunts were placed. In one patient early in the series, the EEG and SSEP were unchanged but the rSO(2) dropped precipitously, and a shunt was placed. In the 299 patients who showed no discrepancies, 285 were not shunted and 14 required a shunt. Two strokes occurred in the entire series (0.6%), none intraoperatively. Shunts were placed in 23 patients (7%). The sensitivity of rSO(2) compared with EEG/SSEP was 68%, and the specificity was 94%. This gave a positive-predictive value of 47% and a negative-predictive value of 98%. CONCLUSIONS: Relying on rSO(2) alone for selective shunting is potentially dangerous and might have led to intraoperative ischemic strokes in seven patients and the unnecessary use of shunts in at least 16 patients in this series. The use of rSO(2) adds nothing to the information already provided by EEG and SSEP in determining when to place a shunt during CEA.

    Title Weight Loss Strategies Associated with Bmi in Overweight Adults with Type 2 Diabetes at Entry into the Look Ahead (action for Health in Diabetes) Trial.
    Date August 2008
    Journal Diabetes Care
    Excerpt

    Intentional weight loss is recommended for those with type 2 diabetes, but the strategies patients attempt and their effectiveness for weight management are unknown. In this investigation we describe intentional weight loss strategies used and those related to BMI in a diverse sample of overweight participants with type 2 diabetes at enrollment in the Look AHEAD (Action for Health in Diabetes) clinical trial.

    Title Nitric Oxide Production of T Lymphocytes is Increased in Rheumatoid Arthritis.
    Date August 2008
    Journal Immunology Letters
    Excerpt

    Experimental and clinical evidence for T cell involvement in the pathology of rheumatoid arthritis (RA) is compelling, and points to a local dysregulation of T cell function in the inflamed joint. Nitric oxide (NO) has been shown to regulate T cell function under physiological conditions, but overproduction of NO may contribute to lymphocyte dysfunction characteristic of RA. Several investigations in patients with RA have documented evidence of increased NO synthesis, but these studies have focused largely on macrophage-derived NO and its impact on innate immune and inflammatory responses. In this study, we set out to explore the contribution that T cells make to NO production. We find that T cells from RA patients produce >2.5 times more NO than healthy donor T cells (p<0.001). Although NO is an important physiological mediator of mitochondrial biogenesis, mitochondrial mass is similar in RA and control T cells. In contrast, increased NO production is associated with increased cytoplasmic Ca(2+) concentrations in RA T cells (p<0.001). In vitro treatment of human peripheral blood lymphocytes, or Jurkat cells with TNF increases NO production (p=0.006 and p=0.001, respectively), whilst infliximab treatment in RA patients decreases T cell derived NO production within 6 weeks of the first infusion (p=0.005). Together, these data indicate that TNF induced NO production in T lymphocytes may contribute to perturbations of immune homeostasis in RA.

    Title Hepatic Fat and Adenosine Triphosphate Measurement in Overweight and Obese Adults Using 1h and 31p Magnetic Resonance Spectroscopy.
    Date June 2008
    Journal Liver International : Official Journal of the International Association for the Study of the Liver
    Excerpt

    BACKGROUND/AIMS: Magnetic resonance spectroscopy (MRS) measures hepatic fat and adenosine triphosphate (ATP), but magnetic resonance studies are challenging in obese subjects. We aimed to evaluate the inter- and intrarater reliability and stability of hepatic fat and ATP measurements in a cohort of overweight and obese adults. METHODS: We measured hepatic fat and ATP using proton MRS ((1)H MRS) and phosphorus MRS ((31)P MRS) at baseline in adults enrolled in the Action for Health in Diabetes (Look AHEAD) clinical trial at one site. Using logistic regression, we determined factors associated with successful MRS data acquisition. We calculated the intra- and inter-rater reliability for hepatic fat and ATP based on 20 scans analysed twice by two readers. We also calculated the stability of these measures three times on five healthy volunteers. RESULTS: Of 244 participants recruited into our ancillary study, 185 agreed to MRS. We obtained usable hepatic fat data from 151 (82%) and ATP data from 105 (58%). Obesity was the strongest predictor of failed data acquisition; every unit increase in the body mass index reduced the likelihood of successful fat data by 11% and ATP data by 14%. The inter- and intrarater reliability were excellent for fat (intraclass correlation coefficient=0.99), but substantially more variable for ATP. Fat measures appeared relatively stable, but this was less true for ATP. CONCLUSIONS: Obesity can hinder (1)H and (31)P MRS data acquisition and subsequent analysis. This impact was greater for hepatic ATP than hepatic fat.

    Title Video-assisted Transumbilical Meckel's Diverticulectomy in Children.
    Date June 2008
    Journal The American Surgeon
    Excerpt

    The treatment of Meckel's diverticulum (MD) in children is resection. Some data exist for the use of laparoscopic resection. The Video-Assisted Transumbilical (VAT) single-trocar technique has been recently described for appendectomy. We also have used this technique for the resection of MD. The purpose of this study is to report our experience with laparoscopic-assisted resection of MD using both the three-trocar and the single-trocar techniques. The Institutional Review Board approved our retrospective chart review of all patients with the diagnosis of MD. Only the cases that were treated via laparoscopy were included. Technique of resection was at the discretion of the surgeon. Nine patients underwent laparoscopic resection of an MD from 2000 to 2005. Four patients underwent the three-trocar technique (LAP n = 4) and the remaining five underwent the video-assisted transumbilical single-trocar technique (VAT n = 5) procedure. Indications for surgery included gastrointestinal bleeding (VAT n = 3; LAP n = 2), malrotation (LAP n = 2), intussusception (VAT n = 1), and abdominal pain (VAT n = 1). All patients were male, and ages ranged from 7 months to 17 years for the VAT group and 8 months to 15 years for the LAP group. The average length of surgery for the LAP versus VAT was 128 minutes (94-170 minutes) and 81.4 minutes (42-96 minutes) respectively. Of the five patients undergoing LAP, two Ladd's procedures and three appendectomies were included during the same anesthesia. Only a single appendectomy procedure was performed during a VAT. The average time until full feeds with the LAP and VAT was 4.3 days (2-8 days) and 2.0 days (1-3 days) respectively. The overall length of stay with LAP versus VAT was 4.3 days (2-8 days) and 3.7 days (2-5 days). Only one case using the LAP method required conversion to an open laparotomy. Though no randomized trial for the removal of MD exists, our data suggest that the use of laparoscopy for removal of both symptomatic and asymptomatic MD is safe and effective. Additionally, the one trocar technique is feasible and may be beneficial in terms of fewer incisions and operative costs; however, more patients need to be studied.

    Title The Influence of Organic Acids in Relation to Acid Deposition in Controlling the Acidity of Soil and Stream Waters on a Seasonal Basis.
    Date May 2008
    Journal Environmental Pollution (barking, Essex : 1987)
    Excerpt

    Much uncertainty still exists regarding the relative importance of organic acids in relation to acid deposition in controlling the acidity of soil and surface waters. This paper contributes to this debate by presenting analysis of seasonal variations in atmospheric deposition, soil solution and stream water chemistry for two UK headwater catchments with contrasting soils. Acid neutralising capacity (ANC), dissolved organic carbon (DOC) concentrations and the Na:Cl ratio of soil and stream waters displayed strong seasonal patterns with little seasonal variation observed in soil water pH. These patterns, plus the strong relationships between ANC, Cl and DOC, suggest that cation exchange and seasonal changes in the production of DOC and seasalt deposition are driving a shift in the proportion of acidity attributable to strong acid anions, from atmospheric deposition, during winter to predominantly organic acids in summer.

    Title Quantitative Comparison and Evaluation of Software Packages for Assessment of Abdominal Adipose Tissue Distribution by Magnetic Resonance Imaging.
    Date May 2008
    Journal International Journal of Obesity (2005)
    Excerpt

    OBJECTIVE: To examine five available software packages for the assessment of abdominal adipose tissue with magnetic resonance imaging, compare their features and assess the reliability of measurement results.Design:Feature evaluation and test-retest reliability of softwares (NIHImage, SliceOmatic, Analyze, HippoFat and EasyVision) used in manual, semi-automated or automated segmentation of abdominal adipose tissue. SUBJECTS: A random sample of 15 obese adults with type 2 diabetes. MEASUREMENTS: Axial T1-weighted spin echo images centered at vertebral bodies of L2-L3 were acquired at 1.5 T. Five software packages were evaluated (NIHImage, SliceOmatic, Analyze, HippoFat and EasyVision), comparing manual, semi-automated and automated segmentation approaches. Images were segmented into cross-sectional area (CSA), and the areas of visceral (VAT) and subcutaneous adipose tissue (SAT). Ease of learning and use and the design of the graphical user interface (GUI) were rated. Intra-observer accuracy and agreement between the software packages were calculated using intra-class correlation. Intra-class correlation coefficient was used to obtain test-retest reliability. RESULTS: Three of the five evaluated programs offered a semi-automated technique to segment the images based on histogram values or a user-defined threshold. One software package allowed manual delineation only. One fully automated program demonstrated the drawbacks of uncritical automated processing. The semi-automated approaches reduced variability and measurement error, and improved reproducibility. There was no significant difference in the intra-observer agreement in SAT and CSA. The VAT measurements showed significantly lower test-retest reliability. There were some differences between the software packages in qualitative aspects, such as user friendliness. CONCLUSION: Four out of five packages provided essentially the same results with respect to the inter- and intra-rater reproducibility. Our results using SliceOmatic, Analyze or NIHImage were comparable and could be used interchangeably. Newly developed fully automated approaches should be compared to one of the examined software packages.

    Title Development and Application of a Novel Environmental Preference Chamber for Assessing Responses of Laboratory Mice to Atmospheric Ammonia.
    Date May 2008
    Journal Journal of the American Association for Laboratory Animal Science : Jaalas
    Excerpt

    A novel environmental preference chamber (EPC) was developed and used to assess responses of laboratory mice to atmospheric ammonia. The EPC features 1) a test chamber with 4 individually ventilated, mutually accessible compartments; b) automated tracking of mouse movements by using paired infrared sensors; c) identification of individual mice by using photosensors; d) monitoring and regulation of the NH3 concentration in each compartment; and e) personal-computer-based data acquisition. In an initial preference study with the EPC, 4 groups of 4 laboratory mice (BALB/c/Bkl; body weight, 13.4 to 18.4 g) were each given a choice among 4 NH3 concentrations (mean +/- SE) of 4 +/- 2, 30 +/- 2, 56 +/- 4, and 110 +/- 6 ppm for 2 d after a 2-d familiarization period. Once trained to use the intercompartment tunnels, the mice made extensive use of the EPC, with each group making more than 2000 intercompartment movements during 48 h. Video recording verified the results of the automatic tracking system, which detected and correctly determined mouse location for 79% of the moves. The use of photosensors proved to be ineffective in recognizing individual mice. Although the EPC would benefit from refinement and further development, it simplified analysis of locomotion behavioral data. Results of the preference study indicated that the mice exhibited no clear preference for, or aversion to, any of the experimental concentrations of ammonia and that the mice clearly preferred the upper 2 compartments of the chamber over the lower 2 compartments. Further investigation should be conducted to verify these preliminary results and explore other preferences of laboratory mice for environmental conditions and resources.

    Title A Community Stroke Study: Factors Influencing Stroke Awareness and Hospital Arrival Time.
    Date April 2008
    Journal Journal of Stroke and Cerebrovascular Diseases : the Official Journal of National Stroke Association
    Excerpt

    One reason patients do not receive thrombolytic therapy for the treatment of stroke is late arrival to the emergency department (ED). One factor could be due to lack of awareness of stroke symptoms. We tested our hypothesis at 2 hospitals in central Illinois.

    Title Brief Communication: Clinical Implications of Short-term Variability in Liver Function Test Results.
    Date March 2008
    Journal Annals of Internal Medicine
    Excerpt

    Clinicians sometimes order liver tests as part of a screening examination or general work-up. Current guidelines do not recommend routine retesting of abnormal results in asymptomatic patients.

    Title A New Ivermectin Formulation Topically Kills Permethrin-resistant Human Head Lice (anoplura: Pediculidae).
    Date March 2008
    Journal Journal of Medical Entomology
    Excerpt

    This study examines the effectiveness of a new ivermectin formulation for the topical treatment of the human head louse, Pediculus humanus capitis De Geer (Anoplura: Pediculidae). Permethrin-resistant lice originally obtained from south Florida and maintained on an in vitro rearing system were 100% susceptible to ivermectin formulations by using a semiclinical hair tuft bioassay. The formulation was 100% effective at killing lice using 1, 0.5, and 0.25% ivermectin concentrations after 10-min exposures. As judged by the lethal time (LT)50 and LT95 values, 0.5% formulated ivermectin was 3.8 and 3.2 times faster at killing lice, respectively, than 0.5% nonformulated ivermectin, indicating that the formulation may facilitate the penetration of ivermectin into the louse. The hair tuft-based bioassay in conjunction with the in vitro rearing system provides a standardized method to assess the comparative efficacy of pediculicide formulations in a reproducible format that mimics the exposure scenario that occurs on the human scalp.

    Title Correlation Between Internal Rotation and Bony Anatomy in the Hip.
    Date March 2008
    Journal Clinical Orthopaedics and Related Research
    Excerpt

    Femoroacetabular impingement has been implicated as a risk factor for degenerative arthritis in young people with normally concentric hips. On presentation, patients with impingement have groin pain, limited internal rotation in 90 degrees flexion, and focal articular lesions. We hypothesized that the amount of internal rotation is dictated primarily by the underlying bony anatomy and not secondary to contractures. We compared 23 consecutive patients (32 hips) with 40 asymptomatic control subjects using positional magnetic resonance imaging, physical examination, and a questionnaire regarding symptoms and their commencement. There was a strong correlation between internal rotation in 90 degrees flexion and the measurable free space between the relevant bony contours on magnetic resonance imaging (r = 0.97) in the patient group and the control subjects. The range of internal rotation is closely related to skeletal anatomy, and internal rotation can be used as a noninvasive tool to predict the risk of impingement.

    Title Suboptimal Control of Glycemia, Blood Pressure, and Ldl Cholesterol in Overweight Adults with Diabetes: the Look Ahead Study.
    Date March 2008
    Journal Journal of Diabetes and Its Complications
    Excerpt

    BACKGROUND: The characteristics associated with meeting goals for glycemia, blood pressure (BP), and low-density lipoprotein (LDL) cholesterol for participants with diabetes were examined. METHODS: Baseline information on demographics, medical history, and anthropometry, as well as on hemoglobin A1c, BP, and LDL cholesterol levels, was measured in 5145 participants of Look AHEAD, a multicenter randomized trial performed to determine whether long-term weight loss and increased physical fitness reduce cardiovascular disease (CVD) in overweight and obese individuals with type 2 diabetes. Logistic regression was used to analyze these cross-sectional data to ascertain associations between participant characteristics and attainment of risk factor goals [hemoglobin A1c <7.0%, BP <130/80 mmHg, and LDL <100 mg/dl]. RESULTS: The study population had a mean age of 58.7 years and a mean body mass index of 36.0 kg/m(2). Of the total number of participants, 59.5% were female, 36.8% were of ethnic/racial minority, and 87.3% were on diabetes medications. Upon enrollment, 45.8% had hemoglobin A1c<7.0%, 51.7% had BP<130/80 mmHg, and 37.2% had LDL<100 mg/dl. All three goals were met by only 10.1%. We found consistent evidence for differences in risk factor control by age, gender, race/ethnicity, degree of obesity, education, income, CVD, source of medical care, and medication use. In multivariable analysis, African-American race, increasing degree of obesity, insulin use, and nonutilization of a lipid-lowering agent were associated with not meeting all risk factor goals. CONCLUSION: These data demonstrate that numerous baseline characteristics are associated with suboptimal control of these cardiovascular risk factors among overweight and obese adults with diabetes.

    Title Body Lice and Head Lice (anoplura: Pediculidae) Have the Smallest Genomes of Any Hemimetabolous Insect Reported to Date.
    Date January 2008
    Journal Journal of Medical Entomology
    Excerpt

    The human body louse, Pediculus humanus humanus L. (Anoplura: Pediculidae), is a vector of several diseases, including louse-borne epidemic typhus, relapsing fever, and trench fever, whereas the head louse, Pediculus humanus capitis De Geer (Anoplura: Pediculidae), is more a pest of social concern. Sequencing of the body louse genome has recently been proposed and undertaken by National Human Genome Research Institute. One of the first steps in understanding an organism's genome is to determine its genome size. Here, using flow cytometry determinations, we present evidence that body louse genome size is 104.7 +/- 1.4 Mb for females and 108.3 +/- 1.1 Mb for males. Our results suggest that head lice also have a small genome size, of similar size to the body louse. Thus, Pediculus lice have one of the smallest genome sizes known in insects, suggesting it may be a suitable choice as a minimal hemimetabolous genome.

    Title Nitric Oxide, Chronic Inflammation and Autoimmunity.
    Date October 2007
    Journal Immunology Letters
    Excerpt

    Whilst many physiological functions of nitric oxide (NO) have been revealed so far, recent evidence proposes an essential role for NO in T lymphocyte activation and signal transduction. NO acts as a second messenger, activating soluble guanyl cyclase and participating in signal transduction pathways involving cyclic GMP. NO modulates mitochondrial events that are involved in apoptosis and regulates mitochondrial biogenesis in many cell types, including lymphocytes. Several studies undertaken on patients with RA and SLE have documented increased endogenous NO synthesis, although the effects of NO may be distinct. Here, we discuss recent evidence that NO contributes to T cell dysfunction in both SLE and RA by altering multiple signaling pathways in T cells. Although NO may play a physiological role in lymphocyte cell signaling, its overproduction may perturb T cell activation, differentiation and effector responses, each of which may contribute in different ways to the pathogenesis of autoimmunity.

    Title Memories of Chicago.
    Date August 2007
    Journal Annals of Internal Medicine
    Title Pyrethroid Action on Calcium Channels: Neurotoxicological Implications.
    Date July 2007
    Journal Invertebrate Neuroscience : In
    Excerpt

    Actions of cismethrin versus deltamethrin were compared using two functional attributes of rat brain synaptosomes. Both pyrethroids increased calcium influx but only deltamethrin increased Ca(2+)-dependent neurotransmitter release following K(+)-stimulated depolarization. The action of deltamethrin was stereospecific, concentration-dependent, and blocked by omega-conotoxin GVIA. These findings delineate a separate action for deltamethrin and implicate N-type rat brain Ca(v)2.2 voltage-sensitive calcium channels (VSCC) as target sites that are consistent with the in vivo release of neurotransmitter caused by deltamethrin. Deltamethrin (10(-7) M) reduced the peak current (approx. -47%) of heterologously expressed wild type Ca(v)2.2 in a stereospecific manner. Mutation of threonine 422 to glutamic acid (T422E) in the alpha(1)-subunit results in a channel that functions as if it were permanently phosphorylated. Deltamethrin now increased peak current (approx. +49%) of T422E Ca(v)2.2 in a stereospecific manner. Collectively, these results substantiate that Ca(v)2.2 is directly modified by deltamethrin but the resulting perturbation is dependent upon the phosphorylation state of Ca(v)2.2. Our findings may provide a partial explanation for the different toxic syndromes produced by these structurally-distinct pyrethroids.

    Title Effect of Maternal Asthma on Birthweight and Neonatal Outcome in a British Inner-city Population.
    Date July 2007
    Journal Paediatric and Perinatal Epidemiology
    Excerpt

    During pregnancy, asthma-related alterations in placental function and the maternal immune system, and reduced growth affecting female but not male fetuses have been reported in a study of selected Australian women. The objective of this study was to evaluate the effect of asthma management, declared during pregnancy, on birthweight and neonatal outcome at an inner-city hospital in England. Between June 2001 and December 2003, women at antenatal clinics were questioned about asthma (n = 10 983). Women with asthma and singleton uncomplicated pregnancies ending at term were selected (n = 718), with non-asthmatic controls (n = 718). Among asthmatic women using inhaled steroids and bronchodilators (n = 170), 43% of the newborn boys had birthweights <10th centile, compared with 27% of controls (P = 0.011; OR 2.51 [95% CI: 1.52, 4.14]). For girls, the proportions were 28% and 27%. In women using bronchodilators only (n = 178) or those declaring no treatment (n = 370), birthweights were not significantly reduced. Taking account of smoking, ethnicity, gestational age and parity, there was a mean birthweight reduction with inhaled steroids and bronchodilators of 118 g [95% CI 36.0, 199.0 g] compared with the control group. There was no interaction between the effect of asthma treatment and infant gender. Infants of asthmatic women in the three subgroups who required intensive care were more likely to exhibit transient tachypnoea of the newborn than infants of control women (P < 0.005). In our population-based sample, the risk of low birthweight among asthmatic women did not depend on infant gender, while neonatal respiratory morbidity remains a significant health issue in boys and girls.

    Title Risk Factors for Venous Gas Emboli After Decompression from Prolonged Hyperbaric Exposures.
    Date July 2007
    Journal Aviation, Space, and Environmental Medicine
    Excerpt

    INTRODUCTION: The physical forces governing gas phase nucleation and growth in a liquid would predict less variation in the development of decompression sickness (DCS) than is known to occur in people. METHODS: In order to gain insight into the causes of biological susceptibility to DCS, we analyzed a dataset containing 250 human steady-state hyperbaric exposures using multivariate ordinal and linear regression analysis for relationships between venous gas emboli (VGE) and exposure parameters and subject characteristics. RESULTS: In both previously published data and new chamber exposure data, we found that the strongest predictor of VGE magnitude after decompression was the duration and depth of the hyperbaric exposure, as predicted. Of the subject factors, only age was significantly associated with VGE; body mass index (BMI) and gender were not. The relationship between age and VGE strengthened with decompression magnitude. DISCUSSION: These results suggest that the physiology of aging interacts with the mechanism of VGE generation, altering the risk of DCS after decompression.

    Title Elimination of Fluoroscopy Use in a Pediatric Electrophysiology Laboratory Utilizing Three-dimensional Mapping.
    Date June 2007
    Journal Pacing and Clinical Electrophysiology : Pace
    Excerpt

    The aim of this study was to quantify fluoroscopy use in catheter ablation procedures using a three-dimensional mapping system as the primary source of catheter guidance.

    Title Reduction in Weight and Cardiovascular Disease Risk Factors in Individuals with Type 2 Diabetes: One-year Results of the Look Ahead Trial.
    Date June 2007
    Journal Diabetes Care
    Excerpt

    OBJECTIVE: The effectiveness of intentional weight loss in reducing cardiovascular disease (CVD) events in type 2 diabetes is unknown. This report describes 1-year changes in CVD risk factors in a trial designed to examine the long-term effects of an intensive lifestyle intervention on the incidence of major CVD events. RESEARCH DESIGN AND METHODS: This study consisted of a multicentered, randomized, controlled trial of 5,145 individuals with type 2 diabetes, aged 45-74 years, with BMI >25 kg/m2 (>27 kg/m2 if taking insulin). An intensive lifestyle intervention (ILI) involving group and individual meetings to achieve and maintain weight loss through decreased caloric intake and increased physical activity was compared with a diabetes support and education (DSE) condition. RESULTS: Participants assigned to ILI lost an average 8.6% of their initial weight vs. 0.7% in DSE group (P < 0.001). Mean fitness increased in ILI by 20.9 vs. 5.8% in DSE (P < 0.001). A greater proportion of ILI participants had reductions in diabetes, hypertension, and lipid-lowering medicines. Mean A1C dropped from 7.3 to 6.6% in ILI (P < 0.001) vs. from 7.3 to 7.2% in DSE. Systolic and diastolic pressure, triglycerides, HDL cholesterol, and urine albumin-to-creatinine ratio improved significantly more in ILI than DSE participants (all P < 0.01). CONCLUSIONS: At 1 year, ILI resulted in clinically significant weight loss in people with type 2 diabetes. This was associated with improved diabetes control and CVD risk factors and reduced medicine use in ILI versus DSE. Continued intervention and follow-up will determine whether these changes are maintained and will reduce CVD risk.

    Title A Prospective Study of Plasma Ferritin Level and Incident Diabetes: the Atherosclerosis Risk in Communities (aric) Study.
    Date May 2007
    Journal American Journal of Epidemiology
    Excerpt

    The authors performed a case-cohort study nested within the Atherosclerosis Risk in Communities (ARIC) Study to determine the association between plasma ferritin level and risk of type 2 diabetes mellitus. Persons with incident cases of type 2 diabetes diagnosed over an average follow-up period of 7.9 years (n = 599) were compared with a random sample of the cohort (n = 690). After adjustment for age, gender, menopausal status, ethnicity, center, smoking, and alcohol intake, the hazard ratio for diabetes, comparing the fifth quintile of ferritin with the first quintile, was 1.74 (95% confidence interval: 1.14, 2.65; p-trend < 0.001). After further adjustment for body mass index and components of the metabolic syndrome, the hazard ratio was 0.81 (95% confidence interval: 0.49, 1.34; p-trend = 0.87). From a causal perspective, there are two alternative interpretations of these findings. Elevated iron stores, reflected in elevated plasma ferritin levels, may induce baseline metabolic abnormalities that ultimately result in diabetes. Alternatively, elevated ferritin may be just one of several metabolic abnormalities related to the underlying process that ultimately results in diabetes, rather than a causal factor for diabetes. Longitudinal studies with repeated measurements of glucose and iron metabolism parameters are needed to establish the role of iron stores and plasma ferritin in diabetes development.

    Title The Theory-practice Gap: Impact of Professional-bureaucratic Work Conflict on Newly-qualified Nurses.
    Date March 2007
    Journal Journal of Advanced Nursing
    Excerpt

    This paper reports the findings from a naturalistic enquiry undertaken in the United Kingdom into the extent to which the ideals and values of the preregistration nursing course are adopted by individual newly educated Registered Nurses.

    Title Sequencing of a New Target Genome: the Pediculus Humanus Humanus (phthiraptera: Pediculidae) Genome Project.
    Date January 2007
    Journal Journal of Medical Entomology
    Excerpt

    The human body louse, Pediculus humanus humanus (L.), and the human head louse, Pediculus humanus capitis, belong to the hemimetabolous order Phthiraptera. The body louse is the primary vector that transmits the bacterial agents of louse-borne relapsing fever, trench fever, and epidemic typhus. The genomes of the bacterial causative agents of several of these aforementioned diseases have been sequenced. Thus, determining the body louse genome will enhance studies of host-vector-pathogen interactions. Although not important as a major disease vector, head lice are of major social concern. Resistance to traditional pesticides used to control head and body lice have developed. It is imperative that new molecular targets be discovered for the development of novel compounds to control these insects. No complete genome sequence exists for a hemimetabolous insect species primarily because hemimetabolous insects often have large (2000 Mb) to very large (up to 16,300 Mb) genomes. Fortuitously, we determined that the human body louse has one of the smallest genome sizes known in insects, suggesting it may be a suitable choice as a minimal hemimetabolous genome in which many genes have been eliminated during its adaptation to human parasitism. Because many louse species infest birds and mammals, the body louse genome-sequencing project will facilitate studies of their comparative genomics. A 6-8X coverage of the body louse genome, plus sequenced expressed sequence tags, should provide the entomological, evolutionary biology, medical, and public health communities with useful genetic information.

    Title Tissue Response and Msx1 Expression After Human Fetal Digit Tip Amputation in Vitro.
    Date January 2007
    Journal Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society
    Excerpt

    Regeneration of mammalian digit tips is well described; however, associated cellular or molecular events have not been studied in humans. We describe an in vitro human fetal model of response to digit tip amputation, and report expression of the transcription repressor Msx1 in the developing and regrowing human digit tip. Human fetal digits from specimens ranging from 53 to 117 days' estimated gestational age (EGA) were cultured in a defined serum-free medium with supplemented oxygen for time periods from 4 days to 4 weeks. Histology and immunohistochemistry were performed on paired control and tip-amputated digits. Regrowing tissue covered the cut end of the distal phalanx in digits up to 80 days' EGA. Msx1 expression was detected beneath the nail field in control digits to at least 70 days' EGA and at the regrowing tip of 57-day digits at 4 and 7 days post-amputation. Our results show that human fetal digits regrow tissue in vitro in response to tip amputation. This process appears spatially associated with Msx1 expression. Msx1 expression appears increased at the regrowing tip of 57-day digits by 4 days after amputation.

    Title Intravascular Neutrophil Activation Due to Carbon Monoxide Poisoning.
    Date January 2007
    Journal American Journal of Respiratory and Critical Care Medicine
    Excerpt

    RATIONALE: We hypothesized that platelet-neutrophil interactions occur as a result of acute carbon monoxide (CO) poisoning, and subsequent neutrophil activation triggers events that cause neurologic sequelae. OBJECTIVES: To identify platelet-neutrophil interactions and neutrophil activation in patients and in animal models, and to establish the association between these intravascular events and changes linked to CO-mediated neurologic sequelae in an animal model. MEASUREMENTS AND MAIN RESULTS: Blood was obtained from 50 consecutive patients. Abnormalities were variable depending on the carboxyhemoglobin level at study admission and duration of CO exposure. Platelet-neutrophil aggregates were detected and plasma myeloperoxidase (MPO) concentration was significantly elevated in those with confirmed CO poisoning. Among patients exposed to CO for over 3 h, flow cytometry scans of neutrophils revealed increased surface expression of CD18 and, in some groups, MPO on the cell surface. Animal models revealed consistent evidence of platelet-neutrophil aggregates, neutrophil activation and surface MPO, and plasma MPO elevation. MPO was deposited along the brain vascular lining and colocalized with nitrotyrosine. CO poisoning caused abnormalities in the charge pattern of myelin basic protein (MBP), changes linked to adaptive immunologic responses responsible for neurologic sequelae in this model. Changes did not occur in thrombocytopenic rats, those receiving tirofiban to inhibit platelet-neutrophil interactions, or those receiving L-nitroarginine methyl ester to inhibit nitric oxide synthesis. Alterations in MBP did not occur in CO-poisoned knockout mice lacking MPO. CONCLUSIONS: Acute CO poisoning causes intravascular neutrophil activation due to interactions with platelets. MPO liberated by neutrophils mediates perivascular oxidative stress, which is linked to immune-mediated neurologic sequelae.

    Title Comparing Two Methods of Delivering High-flow Gas Therapy by Nasal Cannula Following Endotracheal Extubation: a Prospective, Randomized, Masked, Crossover Trial.
    Date December 2006
    Journal Journal of Perinatology : Official Journal of the California Perinatal Association
    Excerpt

    We compared two methods of delivering high-flow gas therapy by nasal cannula, applied immediately after planned endotracheal extubations of NICU patients.

    Title Lifetime Weight Patterns in Male Physicians: the Effects of Cohort and Selective Survival.
    Date December 2006
    Journal Obesity (silver Spring, Md.)
    Excerpt

    OBJECTIVE: The natural history of lifetime weight change is not well understood because of conflicting evidence from cross-sectional and longitudinal studies. Cross-sectional analyses find that adult weight is highest at approximately 60 years of age and lower thereafter. Longitudinal analyses have not found this pattern. Our objective was to test whether cohort effects and selective survival may explain the differences observed between cross-sectional and longitudinal studies. RESEARCH METHODS AND PROCEDURES: We analyzed data on white men from the Johns Hopkins Precursors Study (n = 1197). Weight and height were measured at enrollment during medical school. The Precursors Study collected subsequent weight measurements by self-report and follows all participants for mortality. RESULTS: In preliminary analyses that ignored cohort and survival effects, average weight increased 0.16 kg/yr to age 65 (p < 0.001) and declined 0.10 kg/yr thereafter (p = 0.002). When controlling for differing rates of weight change by cohort and survival group, the apparent decline after 65 years of age was mostly explained. DISCUSSION: These data suggest that, in white men, weight increases steadily until age 65 and then plateaus. These findings emphasize the necessity of longitudinal rather than cross-sectional data to describe lifetime weight patterns.

    Title Ventilatory Effects of Prolonged Hyperoxia at Pressures of 1.5-3.0 Ata.
    Date November 2006
    Journal Aviation, Space, and Environmental Medicine
    Excerpt

    It was hypothesized that long-duration exposures to toxic levels of hyperoxia would have effects on respiratory control function or activity.

    Title Expression and Characterization of Recombinant Gamma-tryptase.
    Date October 2006
    Journal Protein Expression and Purification
    Excerpt

    Tryptases are trypsin-like serine proteases whose expression is restricted to cells of hematopoietic origin, notably mast cells. gamma-Tryptase, a recently described member of the family also known as transmembrane tryptase (TMT), is a membrane-bound serine protease found in the secretory granules or on the surface of degranulated mast cells. The 321 amino acid protein contains an 18 amino acid propeptide linked to the catalytic domain (cd), followed by a single-span transmembrane domain. gamma-Tryptase is distinguished from other human mast cell tryptases by the presence of two unique cysteine residues, Cys(26) and Cys(145), that are predicted to form an intra-molecular disulfide bond linking the propeptide to the catalytic domain to form the mature, membrane-anchored two-chain enzyme. We expressed gamma-tryptase as either a soluble, single-chain enzyme with a C-terminal His tag (cd gamma-tryptase) or as a soluble pseudozymogen activated by enterokinase cleavage to form a two-chain protein with an N-terminal His tag (tc gamma-tryptase). Both recombinant proteins were expressed at high levels in Pichia pastoris and purified by affinity chromatography. The two forms of gamma-tryptase exhibit comparable kinetic parameters, indicating the propeptide does not contribute significantly to the substrate affinity or activity of the protease. Substrate and inhibitor library screening indicate that gamma-tryptase possesses a substrate preference and inhibitor profile distinct from that of beta-tryptase. Although the role of gamma-tryptase in mast cell function is unknown, our results suggest that it is likely to be distinct from that of beta-tryptase.

    Title Arsenic Exposure and Type 2 Diabetes: a Systematic Review of the Experimental and Epidemiological Evidence.
    Date October 2006
    Journal Environmental Health Perspectives
    Excerpt

    Chronic arsenic exposure has been suggested to contribute to diabetes development. We performed a systematic review of the experimental and epidemiologic evidence on the association of arsenic and type 2 diabetes. We identified 19 in vitro studies of arsenic and glucose metabolism. Five studies reported that arsenic interfered with transcription factors involved in insulin-related gene expression: upstream factor 1 in pancreatic beta-cells and peroxisome proliferative-activated receptor gamma in preadipocytes. Other in vitro studies assessed the effect of arsenic on glucose uptake, typically using very high concentrations of arsenite or arsenate. These studies provide limited insight on potential mechanisms. We identified 10 in vivo studies in animals. These studies showed inconsistent effects of arsenic on glucose metabolism. Finally, we identified 19 epidemiologic studies (6 in high-arsenic areas in Taiwan and Bangladesh, 9 in occupational populations, and 4 in other populations). In studies from Taiwan and Bangladesh, the pooled relative risk estimate for diabetes comparing extreme arsenic exposure categories was 2.52 (95% confidence interval, 1.69-3.75), although methodologic problems limit the interpretation of the association. The evidence from occupational studies and from general populations other than Taiwan or Bangladesh was inconsistent. In summary, the current available evidence is inadequate to establish a causal role of arsenic in diabetes. Because arsenic exposure is widespread and diabetes prevalence is reaching epidemic proportions, experimental studies using arsenic concentrations relevant to human exposure and prospective epidemiologic studies measuring arsenic biomarkers and appropriately assessing diabetes should be a research priority.

    Title Race and Comorbid Factors Predict Nonalcoholic Fatty Liver Disease Histopathology in Severely Obese Patients.
    Date September 2006
    Journal Surgery for Obesity and Related Diseases : Official Journal of the American Society for Bariatric Surgery
    Excerpt

    PURPOSE: Nonalcoholic fatty liver disease (NAFLD) is a common and potentially serious form of chronic liver disease. Although NAFLD is known to be associated with obesity and some comorbid conditions, less is known about the severity of NAFLD among different racial groups. METHODS: We prospectively studied 237 consecutive morbidly obese patients presenting for bariatric surgery. All patients underwent intraoperative liver biopsy and chart review. After excluding subjects who reported alcohol use (n = 37) or who had missing biopsy data (n = 11), 189 patients were available for analysis. Clinical and laboratory associations with each of the histological components of NAFLD were assessed using multiple logistic regression analysis. RESULTS: The mean age was 43.1 years, 84% were female, and 13% were African American. It was found that 88% had steatosis, including 35% with moderate to severe steatosis (> 33% of hepatocytes involved). Of these patients, 67% had inflammation, 46% had fibrosis, and 45% met Brunt's criteria for NASH. Compared with Caucasians and after adjustment, African Americans had significantly lower odds of severe hepatic pathology, with adjusted odds ratios of 0.1 (P = .02) for the presence of moderate or severe steatosis, 0.2 for inflammation (P = .006), 0.3 for fibrosis (P = .05), and 0.2 for NASH (P = .02). In addition, participants with one or more features of the metabolic syndrome (ie, diabetes, hypertension, or dyslipidemia) or elevated aminotransferase levels had significantly higher odds of severe hepatic histopathology. CONCLUSION: Among obese patients presenting for bariatric surgery, NAFLD is more common in Caucasians, patients with features of the metabolic syndrome, and those with elevated aminotransferase levels.

    Title Weight Loss As a Treatment for Nonalcoholic Fatty Liver Disease.
    Date September 2006
    Journal Journal of Clinical Gastroenterology
    Excerpt

    Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease that can progress to cirrhosis and hepatocellular carcinoma. NAFLD has been associated with obesity and other features of the metabolic syndrome, including insulin resistance, impaired glucose tolerance, and dyslipidemia. As a result, and with a lack of other effective treatments, weight loss achieved through lifestyle modifications (diet and exercise) has been promoted as the standard treatment. However, there is very little empiric evidence to support the effectiveness of weight loss for NAFLD. This article reviews the current literature on the effects of weight loss achieved through lifestyle modification or medications on NAFLD. To date, there have been no randomized controlled trials of weight loss interventions on hepatic pathology. Only three published trials (N = 89 subjects), which include a comparison group, have been published. These studies suggest improvement in liver enzymes and/or hepatic pathology; however, direct between group comparisons are lacking. Four small, nonrandomized studies (N = 59 subjects) have evaluated the effect of weight loss achieved with medications (4 of orlistat, 1 of sibutramine) on NAFLD. These suggest some improvement in liver enzymes and histopathology. Finally, a brief review of observational studies on the association between NAFLD pathology or liver enzymes and diet composition suggests a possible role for the manipulation of macronutrients and/or micronutrients in NAFLD treatment. In summary, there is little empiric evidence to support the role of weight loss achieved through lifestyle modification or medication in the treatment of NAFLD. Rigorously conducted, randomized controlled trials are needed in this area.

    Title The Epidemiology of Nonalcoholic Fatty Liver Disease in Adults.
    Date September 2006
    Journal Journal of Clinical Gastroenterology
    Excerpt

    Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease that has been shown to progress to cirrhosis and hepatocellular carcinoma. This article reviews the prevalence of NAFLD and the factors associated this disorder, and with the more advanced stages of NAFLD, including nonalcoholic steatohepatitis (NASH) and fibrosis. In the general population, the estimated prevalence ranges from 3% to 24%, with most estimates in the 6% to 14% range. NAFLD is extremely common among patients undergoing bariatric surgery, ranging from 84% to 96%. In these patients, 25% to 55% have NASH, 34% to 47% have fibrosis, and 2% to 12% have bridging fibrosis or cirrhosis. NAFLD appears to be most strongly associated with obesity, and insulin resistance states including diabetes and with other features of the metabolic syndrome, such as high triglycerides and low HDL. It appears to be more common in men, and it increases with increasing age and after menopause. Some data suggest that Mexican Americans are more likely to have NAFLD and blacks are less likely compared with non-Hispanic whites. More advanced stages of NAFLD are associated with older age, higher body mass index, diabetes, hypertension, high triglycerides, and/or insulin resistance. An AST/ALT ratio greater >1 may also indicate more severe disease. Although hepatocellular carcinoma can occur in the setting of NAFLD, the risk factors for hepatocellular carcinoma in the setting of NAFLD have not been established. More prospective studies are needed to determine the true risk factors for the development and progression of NAFLD to help identify patients at highest risk who might benefit from treatment trials.

    Title Ovicidal and Adulticidal Activities of Cinnamomum Zeylanicum Bark Essential Oil Compounds and Related Compounds Against Pediculus Humanus Capitis (anoplura: Pediculicidae).
    Date September 2006
    Journal International Journal for Parasitology
    Excerpt

    The toxicity of cinnamon, Cinnamomum zeylanicum, bark essential oil compounds against eggs and adult females of human head louse, Pediculus humanus capitis, was examined using direct contact and vapour phase toxicity bioassays and compared with the lethal activity of their related compounds, benzyl alcohol, cinnamic acid, cinnamyl acetate, 4-hydroxybenzaldehyde and salicylaldehyde, as well as two widely used pediculicides, d-phenothrin and pyrethrum. In a filter-paper contact toxicity bioassay with female lice at 0.25 mg/cm(2), benzaldehyde was 29- and 27-fold more toxic than pyrethrum and d-phenothrin, respectively, as judged by median lethal time (LT(50)) values. Salicylaldehyde was nine and eight times more active than pyrethrum and d-phenothrin, respectively. Pediculicidal activity of linalool was comparable with that of d-phenothrin and pyrethrum. Cinnamomum bark essential oil was slightly less effective than either d-phenothrin or pyrethrum. Benzyl alcohol and (E)-cinnamaldehyde exhibited moderate pediculicidal activity. After 24h of exposure, no hatching was observed with 0.063 mg/cm(2) salicylaldehyde, 0.125 mg/cm(2) benzaldehyde, 0.5mg/cm(2)Cinnamomum bark essential oil, 1.0 mg/cm(2) (E)-cinnamaldehyde, and 1.0 mg/cm(2) benzyl cinnamate. Little or no ovicidal activity was observed with d-phenothrin or pyrethrum. In vapour phase toxicity tests with female lice, benzaldehyde and salicylaldehyde were much more effective in closed containers than in open ones, indicating that the mode of delivery of these compounds was largely due to action in the vapour phase. Neither d-phenothrin nor pyrethrum exhibited fumigant toxicity. Cinnamomum bark essential oil and test compounds described merit further study as potential pediculicides or ovicides for the control of P. h. capitis.

    Title Breath Biomarkers and Non-alcoholic Fatty Liver Disease: Preliminary Observations.
    Date July 2006
    Journal Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
    Excerpt

    Breath biomarkers have the potential to offer information that is similar to conventional clinical tests or they are entirely unique. Preliminary data support the use of breath biomarkers in the study of liver disease, in particular non-alcoholic fatty liver disease (NAFLD). It was evaluated whether breath ethanol, ethane, sulfur compounds and acetone would be associated with hepatic histopathology amongst morbidly obese patients presenting for bariatric surgery. Breath samples were collected during a preoperative visit and compared with liver biopsies obtained during the surgery. A Student's two-tailed t-test was used to compare differences between the two groups. Linear regression was used to analyse associations between the concentrations of breath molecules and independent predictor variables. It was found that breath ethanol, ethane and acetone can be useful biomarkers in patients with NAFLD. In particular, breath ethanol can be associated with hepatic steatosis, and breath acetone can be associated with non-alcoholic steatohepatitis.

    Title Will Opposites Attract? Similarities and Differences in Students' Perceptions of the Stereotype Profiles of Other Health and Social Care Professional Groups.
    Date June 2006
    Journal Journal of Interprofessional Care
    Excerpt

    The extent to which health and social care (HSC) students hold stereotypical views of other HSC professional groups is of great potential importance to team working in health care. This paper explores students' perceptions of different HSC professional groups at the beginning of their university programmes. Findings are presented from an analysis of baseline data collected as part of the New Generation Project longitudinal cohort study which is assessing the impact of interprofessional education over time on a range of variables including stereotyping. Questionnaires were administered to a cohort of over 1200 students from 10 different HSC professional groups entering their first year of university. Stereotypes were measured using a tool adapted from Barnes et al. (2000) designed to elicit stereotype ratings on a range of nine characteristics. The findings confirm that students arrive at university with an established and consistent set of stereotypes about other health and social care professional groups. Stereotypical profiles were compiled for each professional group indicating the distinctive characteristics of the groups as well as the similarities and differences between groups.Midwives, social workers and nurses were rated most highly on interpersonal skills and on being a team player whilst doctors were rated most highly on academic ability. Doctors, midwives and social workers were perceived as having the strongest leadership role, whilst doctors were also rated most highly on decision making. All professions were rated highly on confidence and professional competence and, with the exception of social workers, on practical skills. A comparison of profiles for each professional group reveals that, for example, pharmacists and doctors were perceived as having very similar characteristics as were social workers, midwives and nurses. However, the profiles of nurses and doctors were perceived to be very different. The implications of these similarities and differences are discussed in terms of their potential impact on interprofessional interactions, role boundaries and team working.

    Title Identification of Substrates of Human Protein-tyrosine Phosphatase Ptpn22.
    Date June 2006
    Journal The Journal of Biological Chemistry
    Excerpt

    Stimulation of mature T cells activates a downstream signaling cascade involving temporally and spatially regulated phosphorylation and dephosphorylation events mediated by protein-tyrosine kinases and phosphatases, respectively. PTPN22 (Lyp), a non-receptor protein-tyrosine phosphatase, is expressed exclusively in cells of hematopoietic origin, notably in T cells where it represses signaling through the T cell receptor. We used substrate trapping coupled with mass spectrometry-based peptide identification in an unbiased approach to identify physiological substrates of PTPN22. Several potential substrates were identified in lysates from pervanadate-stimulated Jurkat cells using PTPN22-D195A/C227S, an optimized substrate trap mutant of PTPN22. These included three novel PTPN22 substrates (Vav, CD3epsilon, and valosin containing protein) and two known substrates of PEP, the mouse homolog of PTPN22 (Lck and Zap70). T cell antigen receptor (TCR) zeta was also identified as a potential substrate in Jurkat lysates by direct immunoblotting. In vitro experiments with purified recombinant proteins demonstrated that PTPN22-D195A/C227S interacted directly with activated Lck, Zap70, and TCRzeta, confirming the initial substrate trap results. Native PTPN22 dephosphorylated Lck and Zap70 at their activating tyrosine residues Tyr-394 and Tyr-493, respectively, but not at the regulatory tyrosines Tyr-505 (Lck) or Tyr-319 (Zap70). Native PTPN22 also dephosphorylated TCRzeta in vitro and in cells, and its substrate trap variant co-immunoprecipitated with TCRzeta when both were coexpressed in 293T cells, establishing TCRzeta as a direct substrate of PTPN22.

    Title Sequencing and Characterization of a Cdna Encoding a Ferritin Subunit of Colorado Potato Beetle, Leptinotarsa Decemlineata.
    Date May 2006
    Journal Archives of Insect Biochemistry and Physiology
    Excerpt

    A differentially expressed cDNA fragment (P311) from Colorado potato beetle (CPB), Leptinotarsa decemlineata (Say), was identified by restriction fragment differential display-polymerase chain reaction (RFDD-PCR) technique, and showed a strong similarity to ferritin heavy chain subunits of other organisms. Based on P311, we constructed specific primers and obtained a 840-bp cDNA fragment spanning the open reading frame of CPB ferritin subunit using the rapid amplification of cDNA ends (RACE) technique. The sequence encodes 213 amino acid residues, including a 19 amino acid signal peptide. The sequence has a conserved cysteine in the N-terminus and has the seven conserved residues that comprise the ferroxidase center, which is the feature of heavy chain ferritins of vertebrates. The CPB ferritin subunit has high amino acid sequence identity with the Apriona germari (69.3%), Galleria mellonela (54.5%), Manduca sexta (54.0%), Drosophila melanogaster (53.2%), Calpodes ethlius (51.4%), and Nilaparvata lugens (47.6%) but lower identity with the Anopheles gambiae (38.7%) and Aedes aegypti (37.8%). Using Northern blot analysis, the subunit mRNA was identified from fat body and midgut of 4th instars with much higher mRNA levels found in midgut than that in fat body (2.5-fold). Nevertheless, only the levels of mRNA in fat body was induced by dexamethasone (1.5-fold).

    Title Using a Freeze Substitution Fixation Technique and Histological Crimp Analysis for Characterizing Regions of Strain in Ligaments Loaded in Situ.
    Date May 2006
    Journal Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society
    Excerpt

    Type I collagen fibrils in tendons and ligaments assume a sinusoidal wave shape, or crimp, which straightens only with tensile load. The load response of crimp has been studied primarily in isolated subunits and not in complex, intact structures. The purpose of our study was to determine if freeze substitution fixation of an entire ligament could preserve changes in crimp morphology induced by functionally relevant loading conditions. We hypothesized that, in ligaments prepared by freeze-substitution fixation under load, crimp would progressively extinguish with increasing loads, and nonuniform strain following partial section could be detected from crimp morphology. Tensile loads ranging from 0 to 220 N were applied to patellar ligaments of 16 fresh rabbit stifle joints using simulated isometric quadriceps pull through the patella. The loaded joints were flash frozen with isopentane cooled in liquid nitrogen, then fixed using freeze substitution. Another six ligaments were loaded to 150 N following incision of the anterior third and evaluated under polarized light microscopy for crimp distribution. Ligaments with no or low loads could be identified by the presence of crimp on mid-sagittal sections. Strain distribution was inhomogeneous, in that the ligament displayed a consistent pattern of collagen fiber recruitment among three morphologically distinct bands seen on coronal sections. At very low loads (about 18 N), the fibers in a central band were uncrimped; anterior and deep bands uncrimped at higher loads. The crimp in the entire specimen was extinguished at about 67 N, which correlates closely with the previously reported toe-region of the stress-strain curve of the rabbit patellar ligament. When the anterior third was transected, fibers within that segment retained a crimp in ligaments prepared under loads that ordinarily would ablate all crimp. These findings suggest that freeze fixation could be used to map the functional microstructure of ligaments or tendons.

    Title Optimization of Oxygen Tolerance Extension in Rats by Intermittent Exposure.
    Date April 2006
    Journal Journal of Applied Physiology (bethesda, Md. : 1985)
    Excerpt

    Optimization of oxygen tolerance extension by intermittent exposure was studied in groups of 20 rats exposed to systematically varied patterns of alternating oxygen and normoxic breathing periods at 4.0, 2.0, and 1.5 ATA. Oxygen periods of 20, 60, and 120 min were alternated with normoxic intervals that provided oxygen-to-normoxia ratios of 4:1, 2:1, 1:1, and 1:3. In general, median survival times had nearly linear relationships to increasing normoxic intervals with oxygen period held constant. Exceptions occurred at 4.0 and 2.0 ATA where a 5-min normoxic interval was too short for adequate recovery even with a 20-min oxygen period, and an oxygen period of 120 min was too long even with a normoxic interval of 30 min. These exceptions did not occur at 1.5 ATA. Survival time for many intermittent exposure patterns was equivalent to that for continuous exposure to an oxygen pressure definable as a time-weighted average of the alternating oxygen and normoxia periods. However, this predictive method underestimated the degree of protection achieved by several of the intermittent exposure patterns, especially those performed at 4.0 ATA. Results provided guidance for selection of intermittent exposure patterns for direct evaluation in humans breathing oxygen at 2.0 ATA. Definition of intermittent exposure patterns and conditions that produced prominent gains in oxygen tolerance can also facilitate the performance of future experiments designed to study potential mechanisms for oxygen tolerance extension by intermittent exposure. Heat shock and oxidation-specific stress proteins that are induced by exposure to oxidant injury are suggested for emphasis in such investigations.

    Title A National Collaboration to Disseminate Skills for Outpatient Teaching in Internal Medicine: Program Description and Preliminary Evaluation.
    Date April 2006
    Journal Academic Medicine : Journal of the Association of American Medical Colleges
    Excerpt

    The shift of clinical care and teaching to outpatient settings has challenged ambulatory and community-based teachers. To address this challenge, U.S. internal medicine organizations devised "Faculty Development for General Internal Medicine: Generalist Faculty Teaching in Ambulatory Settings," a national program to train leaders to create local faculty development projects. In 1999, teams from all 386 internal medicine training institutions were invited to apply. Participation required an acceptable plan for a local project and inclusion of an institutional leader, residency or clerkship director, and a community-based faculty member on the project team. Team members attended one of three national training conferences held in 1999 and 2000 that included plenary sessions, workshops, and team meetings. Participants were invited to a wrap-up conference to present their accomplishments. One hundred ten teams from 57 university and 53 non-university hospitals attended the training conferences; 412 (93%) participants returned conference evaluations. All sessions were rated highly. Participants preferred workshops and team meetings to plenary sessions. Two hundred thirty-five (57%) would have recommended the training conference to colleagues as an outstanding experience; 148 (36%) as a good experience; and 25 (6%) as a satisfactory experience. Forty-nine teams (122 participants) returned for the wrap up conference where 35 teams presented their local faculty development projects. Cost per team trained was US$11,818. This program demonstrated a national desire for training in teaching skills, reached a broad audience of ambulatory-based clinical teachers, provided highly rated faculty development conferences in teaching skills, and facilitated development of a variety of local projects at modest expense. Partnerships were forged between academic leaders and community-based teachers.

    Title Rheumatoid Arthritis: a Disease of Chronic, Low-amplitude Signals Transduced Through T Cell Antigen Receptors?
    Date April 2006
    Journal Wiener Medizinische Wochenschrift (1946)
    Excerpt

    Technology has advanced to the stage where it is now possible to identify genes that confer low to moderate risk of developing autoimmune diseases such as rheumatoid arthritis (RA). This has been facilitated by the growing appreciation that these hard to detect genetic signals can only be defined in large cohorts of well characterized patients. In RA, the association between disease susceptibility and genes encoded within the MHC has been known for decades. Recent studies have identified several new candidate genes that provide further insights into the molecular nature of aberrant immune responses in chronic inflammatory diseases. Here, we describe some of these new genes. Based on their known functions we propose that in a subgroup of patients with RA inheritance of allelic variants at distinct loci could lead to dysregulation of adaptive immune responses characterized by chronic, low-amplitude signaling transduced by antigen T cell receptors.

    Title Roux-en-y Gastric Bypass Improves Liver Histology in Patients with Non-alcoholic Fatty Liver Disease.
    Date January 2006
    Journal Obesity Research
    Excerpt

    OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in the United States and is prevalent in morbidly obese patients. While weight loss and treatment of risk factors are recommended, the reported effects of bariatric surgery on NAFLD are mixed. RESEARCH METHODS AND PROCEDURES: We examined liver histology at the time of Roux-en-Y gastric bypass surgery and at elective incisional hernia repair after weight loss for 16 patients at one center. Slides were read by one pathologist, blinded to clinical data, using the Brunt criteria. Clinical and laboratory data were extracted from chart review. Alcohol use was ascertained by two interviews. RESULTS: At baseline, the mean age was 44 years, 50% were women, 88% were white, and the mean BMI was 51 kg/m2. None had significant alcohol use. On initial biopsy, all patients showed steatosis, 94% had inflammation, 88% had ballooning degeneration, 88% had perisinusoidal fibrosis, and 81% had portal fibrosis. The mean time between the two biopsies was 305 +/- 131 (SD) days. The mean weight loss was 118 +/- 29 lb. Steatosis improved in 15 of 16 patients, with resolution in 13. Twelve of 15 patients with inflammation at baseline showed improvement, and 12 of 14 showed less ballooning. Six of 14 patients with perisinusoidal fibrosis and 6 of 13 with portal fibrosis showed improvement. No patient had worsening of steatosis, inflammation, ballooning, or fibrosis. DISCUSSION: Our study shows improvement in all of the histological features of NAFLD after Roux-en-Y gastric bypass surgery-induced weight loss, despite significant histopathology at baseline and substantial weight loss.

    Title Racial and Socioeconomic Differences in the Weight-loss Experiences of Obese Women.
    Date November 2005
    Journal American Journal of Public Health
    Excerpt

    Focus groups stratified by race and socioeconomic status were used to examine obese women's experiences with weight-loss methods. Six themes emerged: failure of weight maintenance, use of psychological and spiritual approaches, role of family influences and societal expectations, role of African American subculture, method affordability, and racial differences in weight-loss methods. Tailored weight-management interventions for women, particularly African Americans and those of low socioeconomic status, should account for features of African American subculture and address affordability concerns, include maintenance strategies that incorporate psychological and spiritual principles, and target family attitudes and behaviors.

    Title Hepatic 31p Magnetic Resonance Spectroscopy: a Hepatologist's User Guide.
    Date October 2005
    Journal Liver International : Official Journal of the International Association for the Study of the Liver
    Excerpt

    Hepatic phosphorus magnetic resonance spectroscopy (31P MRS) offers the exciting potential of studying metabolic processes in the human liver in vivo. Many investigators have utilized 31P MRS to research a broad range of metabolic questions, and there is outstanding potential for this imaging modality in the future. However, at times it is difficult to appreciate this potential because most published series have been small, and comparisons between studies are difficult. Indeed, the published literature contains significant variation in data acquisition and data analysis techniques and, perhaps most importantly, the interpretation of the data itself. As MR technology continues to evolve and more studies are being performed, perhaps a greater consensus of study techniques and endpoints will emerge. This review summarizes the present literature on human hepatic 31P MRS.

    Title Pathways of T Cell Activation and Terminal Differentiation in Chronic Inflammation.
    Date September 2005
    Journal Current Drug Targets. Inflammation and Allergy
    Excerpt

    Immune and inflammatory responses are governed by antigen-specific T cells, whose activation, differentiation and effector function are induced by signals delivered via the T cell antigen receptor (TCR) and by costimulatory and cytokine receptors. The molecular events leading to the activation of naïve T cells have been extensively studied and are well characterized. Much less is known about the molecular and biochemical events regulating the activation of T cells in chronic inflammatory diseases such as rheumatoid arthritis (RA). This review examines the current state of knowledge of T cell activation in chronic inflammation, focusing on RA, and summarizes experimental data which indicate that the chronic inflammatory process may profoundly affect TCR and cytokine signal transduction pathways. We present evidence suggesting that in chronic inflammation, the antigen-driven TCR-mediated processes are attenuated, while cytokine-driven effector responses are sustained or even enhanced. The possible implications of this inbalance are discussed.

    Title Efficacy of Three Microbiological Monitoring Methods in a Ventilated Cage Rack.
    Date August 2005
    Journal Comparative Medicine
    Excerpt

    The use of individually ventilated caging (IVC) to house mice presents new challenges for effective microbiological monitoring. Methods that exploit the characteristics of IVC have been developed, but to the authors' knowledge, their efficacy has not been systematically investigated. Air exhausted from the IVC rack can be monitored, using sentinels housed in cages that receive rack exhaust air as their supply air, or using filters placed on the exhaust air port. To aid laboratory animal personnel in making informed decisions about effective methods for microbiological monitoring of mice in IVC, the efficacy of air monitoring methods was compared with that of contact and soiled bedding sentinel monitoring. Mice were infected with mouse hepatitis virus (MHV), mouse parvovirus (MPV), murine rotavirus (agent of epizootic diarrhea of mice [EDIM]), Sendai virus (SV), or Helicobacter spp. All agents were detected using contact sentinels. Mouse hepatitis virus was effectively detected in air and soiled bedding sentinels, and SV was detected in air sentinels only. Mouse parvovirus and Helicobacter spp. were transmitted in soiled bedding, but the efficacy of transfer was dependent on the frequency and dilution of soiled bedding transferred. Results were similar when the IVC rack was operated under positive or negative air pressure. Filters were more effective at detecting MHV and SV than they were at detecting MPV. Exposure of sentinels or filters to exhaust air was effective at detecting several infectious agents, and use of these methods could increase the efficacy of microbiological monitoring programs, especially if used with soiled bedding sentinels. In contemporary mouse colonies, a multi-faceted approach to microbiological monitoring is recommended.

    Title Chemical Conversion of Nocathiacin I to Nocathiacin Ii and a Lactone Analogue of Glycothiohexide Alpha.
    Date June 2005
    Journal Journal of Natural Products
    Excerpt

    Nocathiacin I (1) was converted to its deoxy indole analogue, nocathiacin II (2), another natural product, by a unique and facile chemical process. This process was applied to nocathiacin IV (4), generating the lactone analogue of glycothiohexide alpha (5), which was also prepared from nocathiacin II by a mild hydrolytic process. In contrast to glycothiohexide alpha (3), this lactone analogue (5) was found to exhibit in vivo antibacterial efficacy in an animal (mouse) infection model.

    Title Outcomes of a National Faculty Development Program in Teaching Skills: Prospective Follow-up of 110 Medicine Faculty Development Teams.
    Date March 2005
    Journal Journal of General Internal Medicine : Official Journal of the Society for Research and Education in Primary Care Internal Medicine
    Excerpt

    BACKGROUND: Awareness of the need for ambulatory care teaching skills training for clinician-educators is increasing. A recent Health Resources and Services Administration (HRSA)-funded national initiative trained 110 teams from U.S. teaching hospitals to implement local faculty development (FD) in teaching skills. OBJECTIVE: To assess the rate of successful implementation of local FD initiatives by these teams. METHODS: A prospective observational study followed the 110 teams for up to 24 months. Self-reported implementation, our outcome, was defined as the time from the training conference until the team reported that implementation of their FD project was completely accomplished. Factors associated with success were assessed using Kaplan-Meier analysis. RESULTS: The median follow-up was 18 months. Fifty-nine of the teams (54%) implemented their local FD project and subsequently trained over 1,400 faculty, of whom over 500 were community based. Teams that implemented their FD projects were more likely than those that did not to have the following attributes: met more frequently (P=.001), had less turnover (P=.01), had protected time (P=.01), rated their likelihood of success high (P=.03), had some project or institutional funding for FD (P=.03), and came from institutions with more than 75 department of medicine faculty (P=.03). The cost to the HRSA was $22,033 per successful team and $533 per faculty member trained. CONCLUSIONS: This national initiative was able to disseminate teaching skills training to large numbers of faculty at modest cost. Smaller teaching hospitals may have limited success without additional support or targeted funding.

    Title Nocathiacin I Analogues: Synthesis, in Vitro and in Vivo Biological Activity of Novel Semi-synthetic Thiazolyl Peptide Antibiotics.
    Date March 2005
    Journal Bioorganic & Medicinal Chemistry Letters
    Excerpt

    Several nocathiacin I analogues (4-35) were synthesized and evaluated for their antibacterial activity. Most of these semi-synthetic analogues retained very good in vitro and in vivo antibacterial activity of 1.

    Title Effects of Small Incongruities in a Sheep Model of Osteochondral Autografting.
    Date March 2005
    Journal The American Journal of Sports Medicine
    Excerpt

    BACKGROUND: Exact reconstruction of an osteochondral defect by autogenous transplantation (mosaicplasty) is difficult given the variation in joint surface contour. Clinical and experimental studies do not show the extent to which incongruity can be tolerated in autografting. HYPOTHESIS: Grafted articular cartilage will hypertrophy to correct the incongruity created by recession of the transplanted surface. STUDY DESIGN: Controlled laboratory study. METHODS: To test the response of grafts to incongruities, osteochondral autografts were transplanted from the trochlea to the femoral condyle in adult male sheep stifle joints. In groups of 6 animals, graft surfaces were placed flush, countersunk 1 mm or countersunk 2 mm, then histologically analyzed 6 weeks after surgery. Cartilage thickness, condition of the articular surfaces, and preservation of hyaline characteristics were the primary features compared. RESULTS: Bony union, vascularization, and new bone formation were present in all grafts. Cartilage-to-cartilage healing did not occur. In flush specimens, cartilage changed minimally in thickness and histologic architecture. The specimens countersunk 1 mm demonstrated significant cartilage thickening (54.7% increase, P <.05). Chondrocyte hyperplasia, tidemark advancement, and vascular invasion occurred at the chondroosseous junction, and the surface remained smooth. Cartilage necrosis and fibrous overgrowth were observed in all grafts countersunk 2 mm. CONCLUSIONS: Minimally countersunk autografts possess a capacity for remodeling that can correct initial incongruities while preserving hyaline characteristics. Grafts placed deeper do not restore the contour or composition of the original articular surface. CLINICAL RELEVANCE: If preservation of normal hyaline cartilage is the objective, thin grafted articular cartilage can remodel, but the tolerance for incongruity is limited and probably less than that reported for an intra-articular fracture.

    Title Acetabular Augmentation at Six- to 30-year Follow-up. A Biochemical and Histological Analysis.
    Date February 2005
    Journal The Journal of Bone and Joint Surgery. British Volume
    Excerpt

    In developmental dysplasia of the hip, a deficient acetabulum may be augmented by placing local autogenous iliac osseous graft, or the ilium itself, over the head of the femur with the expectation that the added bone will function as a bearing surface. We analysed this bone obtained en bloc during subsequent surgery which was performed for degenerative osteoarthritis in three patients at 6, 25 and 30 years after the initial augmentation procedure. In each patient, the augmentation comprised of red cancellous bone covered on its articulating surface by a distinct layer of white tissue. Microscopy of this tissue showed parallel rows of spindle-shaped cells lying between linearly arranged collagen bundles typical of joint capsule. Biochemical analysis showed type I collagen, the principal collagen of joint capsule and bone, with no significant quantity of type II collagen, the principal collagen of cartilage. While the added bone produced by acetabular augmentation was durable, histological and biochemical analyses suggested that it had not undergone cartilage metaplasia. The augmented acetabulum articulates with the head of the femur by means of an interposed hip joint capsule.

    Title Articular Cartilage Adjacent to Experimental Defects is Subject to Atypical Strains.
    Date February 2005
    Journal Clinical Orthopaedics and Related Research
    Excerpt

    We tested the hypothesis that articular cartilage adjacent to experimental osteochondral defects is not subject to unusual strains under load. A 2.5-mm drill hole was made in the medial femoral condyle of 15 knees from 10 adult rabbits. Experimental joints were loaded with simulated quadriceps force, then frozen under load and preserved by freeze-substitution fixation. Deformation in the region of the defect was evaluated by scanning electron and light microscopy and compared with nondrilled and nonloaded control knees. To simulate blood clot, alginate was placed into some defects before loading. In loaded knees, articular cartilage at the edge of the drill hole was abnormally flattened and folded into the defect. Opposing tibial cartilage or meniscus intruded into the femoral defect beyond the cement line. Alginate did not prevent incursion of opposing cartilage. In this standard drill-hole model, the articular cartilage defect is occupied by the opposing surface when a joint is loaded. Any tissue growing or surgically implanted in the defect is subject to loading and displacement, therefore complicating attempts to characterize the healing or regenerative potential in similar drill-hole models. Deformation of cartilage at the defect edge suggests load concentration or increased compliance. Either phenomenon would contribute to subsequent degeneration of the cartilage adjacent to defects.

    Title Serum Ferritin and Risk of the Metabolic Syndrome in U.s. Adults.
    Date February 2005
    Journal Diabetes Care
    Excerpt

    We examined the relationship among iron stores, the metabolic syndrome, and insulin resistance.

    Title Healing of Reamed Glenoid Bone Articulating with a Metal Humeral Hemiarthroplasty: a Canine Model.
    Date February 2005
    Journal Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society
    Excerpt

    This study characterizes the healing response of the glenoid after spherical reaming and prosthetic humeral head replacement in a canine model of glenohumeral hemiarthroplasty. The right glenoid of twelve skeletally mature female dogs was reamed to a uniform radius of curvature, removing all cartilage down to bleeding subchondral bone. The glenoid was not resurfaced. The humeral head was replaced with a stemmed metal prosthesis. Post-surgery, the operated limbs were immobilized for seven days, with motion allowed ad libitum thereafter. Fluorescent bone labels were administered to identify bone formation. These procedures were not complicated by instability, infection or death. Six animals were euthanized at 10 week and six more at 24 week. The intact glenohumeral joints were evaluated by gross examination, assessment of glenoid concavity, and light microscopy of methylmethacrylate sections. At 10 week, vascular fibrous tissue partially covered the glenoid, maintaining a concave surface congruent with the prosthetic humeral head. New bone formed at the margin of the glenoid, and the density of the periarticular trabecular bone increased. At 24 week, the healing was more advanced; thick fibrocartilaginous tissue covered the entire glenoid surface. These results demonstrate that spherical glenoid reaming produced a consistent healing response characterized by remodelling of the reamed bony concavity to a congruent, living, smooth, securely attached interface articulating with the humeral prosthesis.

    Title Dietary Composition and Nonalcoholic Fatty Liver Disease.
    Date December 2004
    Journal Digestive Diseases and Sciences
    Excerpt

    Nonalcoholic fatty liver disease (NAFLD) is a common and potentially serious form of chronic liver disease that occurs in patients who do not abuse alcohol. Present dietary recommendations for all Americans, including those with NAFLD, endorse a low-calorie, low-fat diet. However, little is known about the effect of diet composition on liver histopathology in patients with NAFLD. The aim of this study was to determine whether overall calorie intake and diet composition are associated with the severity of NAFLD histopathology. Seventy-four consecutive morbidly obese patients presenting for bariatric surgery from January 2001 to March 2002 were retrospectively reviewed. In addition to a standard surgical and psychological evaluation, all patients underwent a preoperative dietary evaluation using a standardized 24-hr food recall. Food intake was evaluated for total calories and macronutrients and compared to liver histopathology from biopsies routinely obtained during surgery. Associations with the severity of steatosis and the presence of inflammation or fibrosis were assessed separately using chi-square for categorical variables and ANOVA for continuous variables. Further, we conducted multiple logistic regression analyses for each histological outcome. There were no significant associations between either total caloric intake or protein intake and either steatosis, fibrosis, or inflammation. However, higher CHO intake was associated with significantly higher odds of inflammation, while higher fat intake was associated with significantly lower odds of inflammation. In conclusion, present dietary recommendations may worsen NAFLD histopathology.

    Title Insecticidal Activity of Plant Essential Oils Against Pediculus Humanus Capitis (anoplura: Pediculidae).
    Date September 2004
    Journal Journal of Medical Entomology
    Excerpt

    The insecticidal activity of 54 plant essential oils against female Pediculus humanus capitis De Geer was examined using direct contact and fumigation methods, and compared with the lethal activity of delta-phenothrin and pyrethrum, two commonly used pediculicides. In a filter paper contact bioassay with female P. humanus capitis, the pediculicidal activity was more pronounced in eucalyptus, marjoram, pennyroyal, and rosemary oils than in delta-phenothrin and pyrethrum on the basis of LT50 values at 0.0625 mg/cm2. At 0.125 mg/cm2, pediculicidal activity of cade, cardamone ceylon, clove bud, myrtle, rosewood, and sage oils was comparable with that of the test insecticides. In fumigation tests with female P. humanus capitis at 0.25 mg/cm2, eucalyptus, marjoram, pennyroyal, and rosemary oils were more effective in closed containers than in open ones, indicating that the effect of these oils was largely a result of action in the vapor phase. Neither delta-phenothrin nor pyrethrum exhibited fumigant toxicity. The essential oils described herein merit further study as potential control agents for P. humanus capitis.

    Title Slaughter Without Prestunning.
    Date August 2004
    Journal The Veterinary Record
    Title Effects of Removal of the Acetabular Labrum in a Sheep Hip Model.
    Date August 2004
    Journal Osteoarthritis and Cartilage / Oars, Osteoarthritis Research Society
    Excerpt

    The aim of this study was to learn whether partial resection of the acetabular labrum would lead to degenerative arthritis in an ovine model.

    Title Faculty Development Needs.
    Date July 2004
    Journal Journal of General Internal Medicine
    Excerpt

    We compared prior training in 4 areas (general teaching skills, teaching specific content areas, teaching by specific methods and in specific settings, and general professional skills) among community-based teachers based in private practices (N = 61) compared with those in community sites operated by teaching institutions (N = 64) and hospital-based faculty (N = 291), all of whom attended one of three national faculty development conferences. The prevalence of prior training was low. Hospital-based faculty reported the most prior training in all 4 categories, teaching hospital affiliated community-based teachers an intermediate amount, and private practice community-based teachers the least (all P <.05). This association remained after multivariable adjustment for age, gender, and amount of time spent in teaching and clinical activities. Preferences for future training reported frequently by the private practice community-based teachers included: time management (48%); teaching evidence-based medicine (46%); evaluation of learners (38%); giving feedback (39%); outpatient precepting (38%); and "teaching in the presence of the patient" (39%).

    Title Field Validation of Aedes Aegypti (diptera: Culicidae) Age Estimation by Analysis of Cuticular Hydrocarbons.
    Date July 2004
    Journal Journal of Medical Entomology
    Excerpt

    In previous studies, we developed linear regression models to age-grade female Aedes aegypti L. reared and maintained under controlled laboratory conditions. The models were based on temporal differences between two cuticular hydrocarbons, pentacosane (C25H52) and nonacosane (C29H60), which were extracted from Ae. aegypti legs and analyzed by gas-liquid chromatography. These initial models predicted adult female age up to 165 DD (12-15 calendar d at 28 degrees C). The age of older mosquitoes, however, could not be accurately predicted. In this study, our original regression models were tested using age data obtained from mosquitoes maintained in a field laboratory and those that were marked, released, and recaptured in northwestern Thailand. Our field data led to the development of two new regression models: one for the cool-dry season (February-March) and one for the rainy season (July-August). Both models resulted in better estimates of age than the original model and thus improved our ability to predict the age of Ae. aegypti to 15 calendar d. Females older than 15 d can be identified as such, but their exact age cannot yet be estimated. The new models will be useful for epidemiological studies and evaluating the impact of Ae. aegypti control interventions for disease prevention.

    Title Independent Cerebral Vasoconstrictive Effects of Hyperoxia and Accompanying Arterial Hypocapnia at 1 Ata.
    Date July 2004
    Journal Journal of Applied Physiology (bethesda, Md. : 1985)
    Excerpt

    Breathing 100% O2 at 1 atmosphere absolute (ATA) is known to be associated with a decrease in cerebral blood flow (CBF). It is also accompanied by a fall in arterial Pco2 leading to uncertainty as to whether the cerebral vasoconstriction is totally or only in part caused by arterial hypocapnia. We tested the hypothesis that the increase in arterial Po2 while O2 was breathed at 1.0 ATA decreases CBF independently of a concurrent fall in arterial Pco2. CBF was measured in seven healthy men aged 21-62 yr by using noninvasive continuous arterial spin-labeled-perfusion MRI. The tracer in this technique, magnetically labeled protons in blood, has a half-life of seconds, allowing repetitive measurements over short time frames without contamination. CBF and arterial blood gases were measured while breathing air, 100% O2, and 4 and 6% CO2 in air and O2 backgrounds. Arterial Po2 increased from 91.7 +/- 6.8 Torr in air to 576.7 +/- 18.9 Torr in O2. Arterial Pco2 fell from 43.3 +/- 1.8 Torr in air to 40.2 +/- 3.3 Torr in O2. CBF-arterial Pco2 response curves for the air and hyperoxic runs were nearly parallel and separated by a distance representing a 28.7-32.6% decrement in CBF. Regression analysis confirmed the independent cerebral vasoconstrictive effect of increased arterial Po2. The present results also demonstrate that the magnitude of this effect at 1.0 ATA is greater than previously measured.

    Title Ovicidal and Adulticidal Activity of Eucalyptus Globulus Leaf Oil Terpenoids Against Pediculus Humanus Capitis (anoplura: Pediculidae).
    Date June 2004
    Journal Journal of Agricultural and Food Chemistry
    Excerpt

    The toxic effects of Eucalyptus globulus leaf oil-derived monoterpenoids [1,8-cineole, l-phellandrene, (-)-alpha-pinene, 2-beta-pinene, trans-pinocarveol, gamma-terpinene, and 1-alpha-terpineol] and the known Eucalyptusleaf oil terpenoids (beta-eudesmol and geranyl acetate) on eggs and females of the human head louse, Pediculus humanus capitis, were examined using direct contact and fumigation bioassays and compared with the lethal activity of delta-phenothrin and pyrethrum, two commonly used pediculicides. In a filter paper contact bioassay with female P. h. capitis, the pediculicidal activity was more pronounced with Eucalyptus leaf oil than with either delta-phenothrin or pyrethrum on the basis of LT(50) values (0.125 vs 0.25 mg/cm(2)). 1,8-Cineole was 2.2- and 2.3-fold more toxic than either delta-phenothrin or pyrethrum, respectively. The pediculicidal activities of (-)-alpha-pinene, 2-beta-pinene, and (E)-pinocarveol were comparable to those of delta-phenothrin and pyrethrum. l-Phellandrene, gamma-terpinene, and 1-alpha-terpineol were relatively less active than delta-phenothrin and pyrethrum. beta-Eudesmol and geranyl acetate were ineffective. 1-alpha-Terpineol and (E)-pinocaveol were highly effective at 0.5 and 1.0 mg/cm(2), respectively, against P. h. capitis eggs. At 1.0 mg/cm(2), (-)-alpha-pinene, 2-beta-pinene, and gamma-terpinene exhibited moderate ovicidal activity, whereas little or no ovicidal activity was observed with the other terpenoids and with delta-phenothrin and pyrethrum. In fumigation tests with female P. h. capitis at 0.25 mg/cm(2), 1,8-cineole, (-)-alpha-pinene, (E)-pinocarveol, and 1-alpha-terpineol were more effective in closed cups than in open ones, indicating that the effect of the monoterpenoids was largely due to action in the vapor phase. Neither delta-phenothrin nor pyrethrum exhibited fumigant toxicity. Eucalyptus leaf oil, particularly 1,8-cineole, 1-alpha-terpineol, and (E)-pinocaveol, merits further study as potential pediculicides or lead compounds for the control of P. h. capitis.

    Title Teaching the Teachers: National Survey of Faculty Development in Departments of Medicine of U.s. Teaching Hospitals.
    Date June 2004
    Journal Journal of General Internal Medicine : Official Journal of the Society for Research and Education in Primary Care Internal Medicine
    Excerpt

    OBJECTIVE: To determine the prevalence, topics, methods, and intensity of ongoing faculty development (FD) in teaching skills. DESIGN: Mailed survey. PARTICIPANTS: Two hundred and seventy-seven of the 386 (72%) U.S. teaching hospitals with internal medicine residency programs. MEASUREMENTS: Prevalence and characteristics of ongoing FD. RESULTS: One hundred and eight teaching hospitals (39%) reported ongoing FD. Hospitals with a primary medical school affiliation (university hospitals) were more likely to have ongoing FD than non-university hospitals. For non-university hospitals, funding from the Health Resources Services Administration and >50 house staff were associated with ongoing FD. For university hospitals, >100 department of medicine faculty was associated. Ongoing programs included a mean of 10.4 topics (standard deviation, 5.4). Most offered half-day workshops (80%), but 22% offered > or =1-month programs. Evaluations were predominantly limited to postcourse evaluations forms. Only 14% of the hospitals with ongoing FD (5% of all hospitals) had "advanced" programs, defined as offering > or =10 topics, lasting >2 days, and using > or =3 experiential teaching methods. These were significantly more likely to be university hospitals and to offer salary support and/or protected time to their FD instructors. Generalists and hospital-based faculty were more likely to receive training than subspecialist and community-based faculty. Factors facilitating participation in FD activities were supervisor attitudes, FD expertise, and institutional culture. CONCLUSIONS: A minority of U.S. teaching hospitals offer ongoing faculty development in teaching skills. Continued progress will likely require increased institutional commitment, improved evaluations, and adequate resources, particularly FD instructors and funding.

    Title T Cell Receptor Zeta Reconstitution Fails to Restore Responses of T Cells Rendered Hyporesponsive by Tumor Necrosis Factor Alpha.
    Date April 2004
    Journal Proceedings of the National Academy of Sciences of the United States of America
    Excerpt

    Expression and function of the antigen T cell receptor (TCR) play a central role in regulating immune responsiveness. Accordingly, targeting the expression of TCRalphabeta or its associated CD3 subunits profoundly influences T cell development and adaptive immunity. Down-regulation of the invariant TCRzeta chain has been documented in a wide variety of chronic inflammatory and infectious diseases, and is thought to contribute to the paradoxical immune suppression observed in these diseases. Previously, we reported that prolonged exposure of T cell hybridoma clones to tumor necrosis factor alpha (TNF) induces nondeletional and reversible hyporesponsiveness to TCR engagement, associated with down-regulation of TCRzeta chain expression, impaired TCR/CD3 complex assembly, and attenuation of TCR-induced membrane proximal tyrosine phosphorylation. Here, we have tested whether receptor specific T cell responses are rescued in TNF-treated T cell hybridomas by retroviral-mediated expression of zeta-chimeric (C2zeta) receptors or wild-type TCRzeta. Expression of C2zeta receptors at the cell surface is relatively refractory to chronic TNF stimulation. However, C2zeta receptor function depends on association with endogenous TCRzeta chains, whose expression is down-regulated by TNF, and so C2 receptor specific responses are attenuated in TNF-treated T cells. Unexpectedly, overexpression of wild-type TCRzeta maintains cell surface TCR/CD3 complex expression but fails to rescue receptor proximal signaling in TNF-treated T cells, suggesting the existence of hitherto unrecognized mechanisms through which TNF regulates T cell responsiveness. We provide additional evidence that TNF also uncouples distal TCR signaling pathways independently of its effects on TCRzeta expression.

    Title Negative Trials in Nonalcoholic Steatohepatitis: Why They Happen and What They Teach Us.
    Date April 2004
    Journal Hepatology (baltimore, Md.)
    Title The Predictions of Nursing Leaders.
    Date March 2004
    Journal Nursing Times
    Title Factors Associated with Palliative Care Knowledge Among Internal Medicine House Staff.
    Date February 2004
    Journal Journal of Palliative Care
    Excerpt

    PURPOSE: To assess knowledge and associated factors in palliative care. METHODS: Self-administered survey of 88 internal medicine house officers in 1996. RESULTS: Twenty-one interns and 36 residents completed the survey for a response rate of 65%. Most house officers reported 1-5 hours of prior formal training in palliative care, 1-5 hours in pain management, and 6-20 hours in ethics. The mean knowledge score was 75% correct (SD = 8); pain management scores were lowest (70%). Overall, interns had a significantly lower mean score than residents (70% vs. 77%; p = 0.001). In multivariate analysis, only the year of residency was significantly associated with knowledge score; prior formal training in palliative care, pain management, or ethics was not. One third of house officers rated themselves as "not at all" or "only slightly" at ease in caring for a dying patient. These self-ratings were not associated with prior training or knowledge, but were higher in residents compared to interns. CONCLUSIONS: Palliative care knowledge and ease with dying patients were higher in later years of residency but were not associated with prior formal palliative care training. These data highlight the continued need to evaluate and improve training in palliative care and pain management.

    Title Prevalence and Correlates of Obesity in a Community Sample of Individuals with Severe and Persistent Mental Illness.
    Date January 2004
    Journal The Journal of Nervous and Mental Disease
    Excerpt

    Individuals with severe and persistent mental illness (SPMI) have a preponderance of weight problems, possibly even greater than the obesity epidemic in the general population. Although atypical antipsychotics cause weight gain, their contribution to obesity has not been characterized in a community setting where individuals may take multiple psychotropics associated with weight gain. Using survey information including measured height and weight from a random sample of Maryland Medicaid recipients with SPMI, we compared obesity prevalence to the National Health and Nutrition Examination Survey (NHANES III) sample and a Maryland sample (Behavioral Risk Factor Surveillance System) of the general population adjusted to SPMI demographic characteristics. We investigated correlates of obesity in the SPMI sample. The results indicate that both men and especially women with SPMI had a higher prevalence of obesity than the general population; this portends substantial health implications. A fourfold association between atypical antipsychotics and prevalent obesity was found in men but not in women; further work should clarify mechanisms of obesity in the SPMI.

    Title Toward Better Interaction Between Orthopaedists and Researchers.
    Date January 2004
    Journal The Journal of Bone and Joint Surgery. American Volume
    Title The Effectiveness of a Community/academic Health Center Partnership in Decreasing the Level of Blood Pressure in an Urban African-american Population.
    Date November 2003
    Journal Ethnicity & Disease
    Excerpt

    This study investigated the effectiveness of a community-academic health center partnership, utilizing nurse-supervised indigenous community health workers, in decreasing the blood pressure in an urban African-American population. A four-year randomized clinical trial was conducted in the Sandtown-Winchester community, which has an excess prevalence of high blood pressure, in order to test the effectiveness of 2 different levels of intervention intensity on increasing the control of high blood pressure. Community health workers were trained and certified in blood pressure management, monitoring, education and counseling, social support mobilization, and community outreach and follow up. The primary results were a significant decrease in mean systolic and diastolic pressures after both levels of intervention, and a significant increase in the percentage of individuals with controlled high blood pressure. Surprisingly, no differences in results were observed between the 2 levels of intervention intensity. This study supports the use of community-based partnership efforts, and the utilization of indigenous health workers, to enhance the control of high blood pressure in a high-risk, African-American urban population.

    Title For the Patient. Community Health Workers Help to Reduce High Blood Pressure.
    Date November 2003
    Journal Ethnicity & Disease
    Title Permethrin-resistant Human Head Lice, Pediculus Capitis, and Their Treatment.
    Date September 2003
    Journal Archives of Dermatology
    Excerpt

    To compare the pediculicidal activity of Ovide lotion and its active ingredient, 0.5% malathion, with Nix and its active ingredient, 1% permethrin, in permethrin-resistant head lice.

    Title The Prevalence and Etiology of Elevated Aminotransferase Levels in the United States.
    Date July 2003
    Journal The American Journal of Gastroenterology
    Excerpt

    Chronic liver disease is a major cause of morbidity and mortality in the United States. Although often used to detect liver disease, the prevalence and etiology of elevated aminotransferases are unknown. We analyzed data on adults ages 17 yr and older (N = 15,676) from the Third National Health and Nutrition Examination Survey (1988-1994). Participants were classified as having elevated aminotransferase levels if either aspartate aminotransferase or alanine aminotransferase was elevated above normal. Aminotransferase elevation was classified as "explained" if there was laboratory evidence of hepatitis B or C infection, iron overload, or if there was a history of alcohol consumption. Analyses were weighted to provide national estimates. The prevalence of aminotransferase elevation in the United States was 7.9%. Aminotransferase elevation was more common in men compared to women (9.3% vs 6.6%, p = 0.002), in Mexican Americans (14.9%) and non-Hispanic blacks (8.1%) compared to non-Hispanic whites (7.1%, p < 0.001). High alcohol consumption, hepatitis B or C infection and high transferrin saturation were found in only 31.0% of cases. Aminotransferase elevation was unexplained in the majority (69.0%). In both men and women, unexplained aminotransferase elevation was significantly associated with higher body mass index, waist circumference, triglycerides, fasting insulin, and lower HDL; and with type 2 diabetes and hypertension in women (all p < 0.05). Aminotransferase elevation was common in the United States, and the majority could not be unexplained by alcohol consumption, viral hepatitis or hemochromatosis. Unexplained aminotransferase elevation was strongly associated with adiposity and other features of the metabolic syndrome, and thus may represent nonalcoholic fatty liver disease.

    Title Repair of the Unilateral Cleft Lip/nose Deformity.
    Date July 2003
    Journal Facial Plastic Surgery : Fps
    Excerpt

    Successful surgical repair of the unilateral cleft lip and nose deformity, defined as normal orbicularis oris function and near-perfect symmetry of the repaired lip and nose, demands that the surgeon possess complete understanding of the embryology and anatomy of the midfacial defects. The surgical approach to repair of the unilateral cleft lip/nose should place great emphasis on achieving symmetry, not only with the lip segments but also perhaps even more importantly with the nasal tip. The reconstruction should recreate an intact fully functional orbicularis oris muscle across the cleft and camouflage the scar optimally. We have found that modification of the Millard rotation-advancement flap technique, with particular attention to the primary nasal repair, provides the best outcomes. In patients who have undergone primary repair of the lip and/or nose deformity, secondary rhinoplasty is generally required, regardless of the technique used at the primary repair. The degree of nasal deformity, however, is less severe following primary repair of the asymmetric nasal tip. We have found that the sliding flap cheliorhinoplasty, Wang's modification of the Vissarionov technique, provides excellent results for most secondary cleft rhinoplasties.

    Title Nonalcoholic Fatty Liver Disease: an Underrecognized Cause of Cryptogenic Cirrhosis.
    Date July 2003
    Journal Jama : the Journal of the American Medical Association
    Excerpt

    Cryptogenic cirrhosis is a common cause of liver-related morbidity and mortality in the United States. Nonalcoholic fatty liver disease (NAFLD) is now recognized as the most common cause of cryptogenic cirrhosis. However, the diagnosis of cirrhosis in patients with NAFLD appears to be delayed compared with those with other chronic liver diseases and thus carries a higher mortality rate. This delay in diagnosis is illustrated in our case of a 53-year-old man who presented with hepatic hydrothorax and ascites, whose workup revealed cirrhosis due to NAFLD. Although a diagnosis of presumed NAFLD can be made noninvasively, a definitive diagnosis requires a liver biopsy specimen. A biopsy specimen is also important for detecting histologically advanced disease, which may be clinically silent and undetected by aminotransferases or diagnostic imaging. Although there are no proven treatments, recommendations for patients with NAFLD include avoidance of hepatotoxins and aggressive management of associated conditions, such as hypertriglyceridemia and type 2 diabetes mellitus.

    Title Decellularized Dermal Grafting in Cleft Palate Repair.
    Date June 2003
    Journal Archives of Facial Plastic Surgery : Official Publication for the American Academy of Facial Plastic and Reconstructive Surgery, Inc. and the International Federation of Facial Plastic Surgery Societies
    Excerpt

    OBJECTIVE: To assess the efficacy of decellularized dermal grafting used as an adjunct to the performance of primary repair of wide cleft palates. DESIGN: Retrospective review. SETTING: Tertiary referral center for large managed care organization. METHODS: Seven consecutive patients with clefts of the hard and soft palates wider than 15 mm as measured at the posterior edge of the hard palate. Palates were repaired in the standard 2-flap approach with intravelar veloplasty. The decellularized dermal graft (AlloDerm) was applied immediately deep to the oral mucosal closure. Patients were followed up with serial postoperative examination. Palates were assessed for dehiscence, fistula, infection, rejection, scarring, and contracture. RESULTS: There were no fistulas. In 2 patients, the oral mucosa dehisced, exposing the dermal graft. In 2 other cases, nasal mucosal tears were inadvertently created during closure of the nasal layer. In all cases, the decellularized dermal graft mucosalized and, by clinical examination, became incorporated into the wound. There were no cases of local inflammation or infection. The degree of scarring and contracture was indistinguishable from the adjacent scar. CONCLUSIONS: Decellularized dermal graft is safe and effective for use in primary closure of wide clefts involving the hard and soft palates. Its application to wide clefts otherwise at risk of fistula is justified. Its use in repair of an existing fistula is also promising.

    Title Radiation Protection Program for Declared Pregnant Workers at Los Alamos National Laboratory.
    Date May 2003
    Journal Health Physics
    Excerpt

    This article presents an overview of Los Alamos National Laboratory's (LANL) Fetal Radiation Protection Program (FRP) that satisfies the requirements set forth in 10 CFR 835 and LANL's Radiation Protection Program. At LANL, the FRP is one of three components of the larger Reproductive Health Hazards Program, which also includes Occupational Medicine and Industrial Hygiene. Although pregnant employees usually enter the program through Occupational Medicine, coordination with all three groups is achieved. The most important part of the FRP Program is performance of the workplace evaluation at the pregnant worker's workplace. At the meeting between the health physicist and the pregnant employee, the following topics are reviewed: risks to the embryo/fetus of working around sources of ionizing radiation; LANL's requirements and 10 CFR 835 regulations; her dose history; basic methods of radiation protection; and a detailed discussion of the work assignments/locations that enables the health physicist to complete an evaluation of the level of radiological hazards. Interface with her supervisor and the Operational Health Physics health physicist in charge of her work areas is essential in acquiring additional information. All of these data, including the radiation dose history and recommendations for possible work modifications or reassignment, are summarized in the workplace evaluation memo, which becomes part of the pregnant employee's medical file. Using input from LANL's legal staff, the author developed a document titled "Guidance to the Supervisors Regarding Fetal Radiation Protection and Reproductive Health Hazards," which instructs supervisors regarding the requirements and regulations, contact names for workplace evaluations, and, very importantly, how to avoid discriminatory behavior against pregnant employees.

    Title Methyl Parathion in Residential Properties: Relocation and Decontamination Methodology.
    Date May 2003
    Journal Environmental Health Perspectives
    Excerpt

    In November 1994 methyl parathion (MP), a restricted agricultural pesticide, was discovered to have been illegally sprayed within hundreds of residences in Lorain County, Ohio. Surface levels and air concentrations of MP revealed detectable levels of the pesticide 3 years after spraying. Because of the high toxicity of MP (lethal dose to 50% of rats tested [LD50] = 15 mg/kg) and long half-life indoors, risk-based relocation and decontamination criteria were created. Relocation criteria were derived based on levels of p-nitrophenol in urine, a metabolic byproduct of MP exposure. In Ohio, concentrations of MP on surfaces and in the air were also used to trigger relocations. The criteria applied in Ohio underwent refinement as cases of MP misuse were found in Mississippi and then in several other states. The MP investigation (1994-1997) was the largest pesticide misuse case in the nation, ultimately involving the sampling of 9,000 residences and the decontamination of 1,000 properties. This article describes the methodology used for relocation of residents and decontamination of properties having MP.

    Title Chicago Area Methyl Parathion Response.
    Date May 2003
    Journal Environmental Health Perspectives
    Excerpt

    The Illinois Department of Public Health participated in the Chicago, Illinois, area methyl parathion (MP) response with several other federal, state, and local government agencies beginning in April 1997. This response was initiated on evidence that hundreds of homes in the Chicago area were illegally treated for cockroaches with MP over a period of several years. Through applicator receipt books and information reported by property owners and tenants, 968 homes were identified as having been treated with MP. Upon implementation of a response plan developed by the Methyl Parathion Health Sciences Steering Committee, environmental sampling and urine monitoring were provided for eligible households. Environmental sampling was conducted in 903 homes, with MP detected above levels of concern in 596 residences. Residents of these homes were offered urine sampling to determine the extent of exposure to MP. Urine samples were collected and analyzed for p-nitrophenol in 1,913 individuals. Implementation of the protocol resulted in 550 residents being relocated during the remediation of 100 households.

    Title Hepatic Steatosis and Type 2 Diabetes Mellitus.
    Date April 2003
    Journal Current Diabetes Reports
    Excerpt

    Type 2 diabetes is strongly associated with nonalcoholic fatty liver disease (NAFLD), a spectrum of liver damage that ranges from relatively benign hepatic steatosis to potentially fatal cirrhosis. The severities of insulin resistance and liver damage parallel each other, with the greatest prevalence of cirrhosis occurring in cirrhotics. However, it is unknown whether one of these conditions causes the other, or if both are consequences of another process. Experimental evidence suggests that both insulin resistance and NAFLD result from a chronic inflammatory state. The mechanisms driving this chronic inflammation are unknown but might include the egress of products from intestinal bacteria into the portal blood, liver, and systemic circulation to trigger a sustained inflammatory cytokine response in genetically susceptible individuals. More research is needed to evaluate this hypothesis and to determine the benefits of treatments that interrupt this pathogenic cascade.

    Title Highly Potent Non-peptidic Inhibitors of the Hcv Ns3/ns4a Serine Protease.
    Date March 2003
    Journal Bioorganic & Medicinal Chemistry Letters
    Excerpt

    Screening of a diverse set of bisbenzimidazoles for inhibition of the hepatitis C virus (HCV) serine protease NS3/NS4A led to the identification of a potent Zn(2+)-dependent inhibitor (1). Optimization of this screening hit afforded a 10-fold more potent inhibitor (46) under Zn(2+) conditions (K(i)=27nM). This compound (46) binds also to NS3/NS4A in a Zn(2+) independent fashion (K(i)=1microM). The SAR of this class of compounds under Zn(2+) conditions is highly divergent compared to the SAR in the absence of Zn(2+), suggesting two distinct binding modes.

    Title Defining Nonalcoholic Fatty Liver Disease: Implications for Epidemiologic Studies.
    Date January 2003
    Journal Gastroenterology
    Title The 'butterfly' Graft in Functional Secondary Rhinoplasty.
    Date December 2002
    Journal The Laryngoscope
    Excerpt

    OBJECTIVE: To describe a surgical technique (the conchal cartilage "butterfly" graft) which, when used in properly selected patients, has been found to be a dependable method for alleviation of postrhinoplasty internal nasal valve dysfunction. STUDY DESIGN: Retrospective chart review. METHODS: Analysis of consecutive patients with weakness and/or collapse of the upper lateral cartilages following rhinoplasty. Seventy-two patients (37 women and 35 men, age range 17-76 y) had severe nasal obstruction and were found to have indications for this procedure. All patients had undergone at least one rhinoplastic procedure. All patients were followed for a minimum of 2 years after surgery. RESULTS: All 72 patients experienced significant subjective improvement in relative nasal obstruction. Two patients (3%) reported less than total resolution of their difficulty breathing through their nose; the remaining 70 patients (97%) reported complete resolution of their nasal airway problems. No patients reported their postoperative nasal obstruction as the same or worse than their preoperative baseline. Sixty-two patients (86%) reported improvement in the appearance of their nose, 8 patients (11%) felt that their appearance was unchanged, and 2 patients (3%) felt that the appearance of their nose was made worse by the procedure. CONCLUSIONS: Patients presenting with nasal obstruction after rhinoplasty are frequently found to have collapse and/or weakening of their upper lateral cartilages with resulting nasal valve dysfunction. The conchal cartilage "butterfly" graft is a technique which, when properly performed during revision rhinoplasty, yields predictable functional and cosmetic results with minimal morbidity.

    Title Prostatitis-like Symptoms: One Year Later.
    Date December 2002
    Journal Bju International
    Excerpt

    To re-survey (after 1 year) men identified in 1999 as having perineal and/or ejaculatory pain/discomfort severe enough to suggest a clinical diagnosis of chronic prostatitis (using the National Institutes of Health-Chronic Prostatitis Symptom Index, NIH-CPSI), and to compare them with an age-matched population of men who had no prostatitis-like symptoms in the initial survey, to determine the effect of time on specific symptoms associated with the diagnosis of chronic prostatitis.

    Title Modeling Pesticide Volatilization from Turf.
    Date November 2002
    Journal Journal of Environmental Quality
    Excerpt

    Pesticide volatilization models are typically based on equilibrium partitioning of the chemical into solid, liquid, and gaseous phases in the soil environment. In turf systems direct vaporization from vegetation surfaces is a more likely source, and it is difficult to apply equilibrium methods to plant material due to the uncertainties of solid-liquid-gas partitioning. An alternative approach is to assume that pesticide volatilization is governed by the same processes that affect water evaporation. A model was developed in which evapotranspiration values, as determined by the Penman equation, were adjusted to chemical vaporization using ratios of water and chemical saturated vapor pressures and latent heats of vaporization. The model also assumes first-order degradation of pesticide on turf vegetation over time. The model was tested by comparisons of predictions with measurements of volatilization for eight pesticides measured during 3 to 7 d in 11 field experiments. Measured volatilization fluxes ranged from 0.1 to 22% of applied chemical. Pesticides were divided into two groups based on saturated vapor pressures and organic C partition coefficients. One pesticide was selected from each group to calibrate the model's volatilization constant for the group, and the remaining pesticides were used for model testing. Testing results indicated that the model provides relatively conservative estimates of pesticide volatilization. Predicted mean losses exceeded observations by 20%, and the model explained 67% of the observed variation in volatilization fluxes. The model was most accurate for those chemicals that exhibited the largest volatilization losses.

    Title Immediate Reconstruction of Extruded Alloplastic Nasal Implants with Irradiated Homograft Costal Cartilage.
    Date September 2002
    Journal The Laryngoscope
    Excerpt

    OBJECTIVE: To describe a novel surgical protocol for the management of patients presenting with extruded nasal implants. STUDY DESIGN: Retrospective chart review. METHODS: Analysis of consecutive patients presenting with extruded nasal implants from 1986 to 2000. Patients were selected from a large database of revision rhinoplasty cases. Inclusion criteria were: 1) at least one previous rhinoplasty procedure, 2) an extruded nasal implant that was documented preoperatively, 3) immediate reconstruction that was carried out with irradiated homograft costal cartilage (IHCC), and 4) at least 1 year of follow-up recorded, including standard postoperative rhinoplasty photographs. A total of 18 patients met the inclusion criteria and form the basis of this study. Data gathered from the charts included date of surgery, last date of follow-up, location of implant extrusion, alloplastic material, specific use of IHCC for reconstruction, percent of clinical IHCC resorption at last follow-up, and presence of warping of the IHCC. RESULTS: All 18 patients were satisfied with the cosmetic outcomes of their nasal reconstructions. The most common extruded alloplast was Silastic, followed by Gore-Tex (W.L. Gore & Associates, Inc., Flagstaff, AZ). There were no cases of extrusion or infection of the IHCC implant subsequent to immediate reconstruction of the extruded alloplast. Clinical resorption of the IHCC was minimal, with a mean follow-up of 26 months. Only one patient had a complication, warpage, resulting in removal of the IHCC. In that patient, the IHCC still had carving markings on the implant after 2 years in vivo. CONCLUSIONS: In this series of patients, a novel surgical protocol was used. The extruded implant was removed and immediate reconstruction with irradiated rib cartilage was done. All patients were evaluated for postoperative infection, graft extrusion, and satisfaction with cosmetic result. There was one major complication in this series of 18 patients, warping of the IHCC, which necessitated removal and replacement. This approach appears to be a reasonable method for reconstruction of extruded nasal alloplasts.

    Title Shotgun Identification of Protein Modifications from Protein Complexes and Lens Tissue.
    Date August 2002
    Journal Proceedings of the National Academy of Sciences of the United States of America
    Excerpt

    Large-scale genomics has enabled proteomics by creating sequence infrastructures that can be used with mass spectrometry data to identify proteins. Although protein sequences can be deduced from nucleotide sequences, posttranslational modifications to proteins, in general, cannot. We describe a process for the analysis of posttranslational modifications that is simple, robust, general, and can be applied to complicated protein mixtures. A protein or protein mixture is digested by using three different enzymes: one that cleaves in a site-specific manner and two others that cleave nonspecifically. The mixture of peptides is separated by multidimensional liquid chromatography and analyzed by a tandem mass spectrometer. This approach has been applied to modification analyses of proteins in a simple protein mixture, Cdc2p protein complexes isolated through the use of an affinity tag, and lens tissue from a patient with congenital cataracts. Phosphorylation sites have been detected with known stoichiometry of as low as 10%. Eighteen sites of four different types of modification have been detected on three of the five proteins in a simple mixture, three of which were previously unreported. Three proteins from Cdc2p isolated complexes yielded eight sites containing three different types of modifications. In the lens tissue, 270 proteins were identified, and 11 different crystallins were found to contain a total of 73 sites of modification. Modifications identified in the crystallin proteins included Ser, Thr, and Tyr phosphorylation, Arg and Lys methylation, Lys acetylation, and Met, Tyr, and Trp oxidations. The method presented will be useful in discovering co- and posttranslational modifications of proteins.

    Title Nonalcoholic Fatty Liver Disease.
    Date June 2002
    Journal Gastroenterology
    Title Intuition and the Development of Expertise in Surgical Ward and Intensive Care Nurses.
    Date May 2002
    Journal Journal of Advanced Nursing
    Excerpt

    The aim of this study was to explore and identify nurses' clinical expertise in surgical ward and intensive care settings in England. One of the objectives of the study and the focus of this paper was the exploration of these nurses' understanding and use of intuition in the context of their practice.

    Title Obesity and Approaches to Weight in an Urban African-american Community.
    Date April 2002
    Journal Ethnicity & Disease
    Excerpt

    OBJECTIVES: To describe the prevalence of obesity, associated factors, and current approaches to weight in an inner city African-American community. DESIGN: In-home survey by community health interviewers. Setting: Baltimore, Maryland. PARTICIPANTS: 2196 community residents identified in a probability sample of census blocks. MAIN OUTCOME MEASURES: Self-reported height and weight and calculated Body Mass Index (BMI), category of BMI, and stated weight goals. RESULTS: Sixty percent of participants were overweight (BMI> or =25 kg/m2), and 31% were obese (BMI> or =30 kg/m2). In multivariate analysis, women, those earning $15,000-30,000, and those aged 45-60 were more likely to be obese; less likely to be obese were smokers, daily drinkers, and those with "good" or "excellent" health. Sixty-one percent of obese participants reported trying to lose weight, while 36% of normal weight participants were trying to gain weight. Of those trying to lose weight, 35% were using recommended approaches, and 26% received "the professional help they needed to control their weight." CONCLUSIONS: Although obesity was prevalent, few were using recommended weight loss strategies and a significant minority of normal weight participants were trying to gain weight, indicating a need for improved weight management and obesity prevention in the African-American community.

    Title Dna-based Genotyping Techniques for the Detection of Point Mutations Associated with Insecticide Resistance in Colorado Potato Beetle Leptinotarsa Decemlineata.
    Date April 2002
    Journal Pest Management Science
    Excerpt

    Three DNA-based genotyping techniques, bi-directional PCR amplification of specific allele (bi-PASA), single-stranded conformational polymorphism (SSCP) and minisequencing, have been developed and compared for the detection of the S291G (insensitive acetylcholinesterase) and L1014F (insensitive sodium channel) mutations associated with azinphos-methyl and permethrin resistance, respectively, in the Colorado potato beetle (Leptinotarsa decemlineata). Extraction of genomic DNA from individual neonates that were hatched from previously collected egg masses is the most efficient and reliable means to obtain suitable templates in terms of convenience, economy, speed and DNA quality. Bi-PASA, employing two allele-specific primers, appears to be the most efficient and rapid genotyping method for the simultaneous detection of both resistant/susceptible homozygous (SS, RR) and heterozygous (SR) alleles. Its resolution, however, is strongly dependent on the quality of template genomic DNA. SSCP also allows unambiguous genotyping, including the detection of heterozygous alleles, and is less dependent on template DNA quality, but requires a longer processing time. Minisequencing is amenable to a 96-well microtiter plate format for the processing of a large number of samples and allows direct detection of resistant/susceptible homozygous alleles but is not as efficient as the PASA and SSCP in detecting heterozygous alleles. In considering the advantages and disadvantages of each technique, DNA-based genotyping is best employed in combinations, with the bi-PASA as the primary method and the SSCP and minisequencing as the secondary validating methods. These methods are rugged, rapid, cost-effective and capable of resolving SS, RR and SR individuals. The availability of such DNA-based genotyping techniques, using neonate genomic DNA as templates, will enable the precise monitoring of the resistant and susceptible allele frequencies, including those of heterozygote individuals, in field populations of L. decemlineata.

    Title Local Flaps in Scar Revision.
    Date March 2002
    Journal Facial Plastic Surgery : Fps
    Excerpt

    Local and regional skin flaps provide the foundation for reconstructive surgery of the face. When planned and executed properly, local skin flaps provide rapid reconstruction using donor tissue with excellent color and texture match, and a reliable, adequate blood supply. The majority of local skin flaps are utilized for reconstruction after superficial cancer extirpation, however, unfavorable scars from previous trauma, burns, or reconstruction efforts provide the motivated patient and surgeon another opportunity to restore form and function. This article reviews techniques commonly used to reconstruct the face and provides several cases where these techniques were successfully employed.

    Title Mechanisms of Pyrethroid Neurotoxicity: Implications for Cumulative Risk Assessment.
    Date March 2002
    Journal Toxicology
    Excerpt

    The Food Quality Protection Act (FQPA) of 1996 requires the United States Environmental Protection Agency to consider the cumulative effects of exposure to pesticides having a 'common mechanism of toxicity.' This paper reviews the information available on the acute neurotoxicity and mechanisms of toxic action of pyrethroid insecticides in mammals from the perspective of the 'common mechanism' statute of the FQPA. The principal effects of pyrethroids as a class are various signs of excitatory neurotoxicity. Historically, pyrethroids were grouped into two subclasses (Types I and II) based on chemical structure and the production of either the T (tremor) or CS (choreoathetosis with salivation) intoxication syndrome following intravenous or intracerebral administration to rodents. Although this classification system is widely employed, it has several shortcomings for the identification of common toxic effects. In particular, it does not reflect the diversity of intoxication signs found following oral administration of various pyrethroids. Pyrethroids act in vitro on a variety of putative biochemical and physiological target sites, four of which merit consideration as sites of toxic action. Voltage-sensitive sodium channels, the sites of insecticidal action, are also important target sites in mammals. Unlike insects, mammals have multiple sodium channel isoforms that vary in their biophysical and pharmacological properties, including their differential sensitivity to pyrethroids. Pyrethroids also act on some isoforms of voltage-sensitive calcium and chloride channels, and these effects may contribute to the toxicity of some compounds. Effects on peripheral-type benzodiazepine receptors are unlikely to be a principal cause of pyrethroid intoxication but may contribute to or enhance convulsions caused by actions at other target sites. In contrast, other putative target sites that have been identified in vitro do not appear to play a major role in pyrethroid intoxication. The diverse toxic actions and pharmacological effects of pyrethroids suggest that simple additivity models based on combined actions at a single target are not appropriate to assess the risks of cumulative exposure to multiple pyrethroids.

    Title Prostate Carcinoma Metastatic to the Cervical Lymph Nodes: Report of Two Cases and Review of the Literature.
    Date January 2002
    Journal American Journal of Otolaryngology
    Excerpt

    The cervical lymph nodes are a common site of metastasis for cancers originating in the upper aerodigestive tract. Rarely, cancers originating from sites other than the head and neck can metastasize to the cervical lymph node chain. We report on 2 recent patients with metastatic prostate cancer to the cervical lymph nodes.

    Title Long-term Entecavir Treatment Results in Sustained Antiviral Efficacy and Prolonged Life Span in the Woodchuck Model of Chronic Hepatitis Infection.
    Date December 2001
    Journal The Journal of Infectious Diseases
    Excerpt

    Entecavir (ETV) is a guanosine nucleoside analogue with potent antiviral efficacy in woodchucks chronically infected with woodchuck hepatitis virus. To explore the consequences of prolonged virus suppression, woodchucks received ETV orally for 8 weeks and then weekly for 12 months. Of the 6 animals withdrawn from therapy and monitored for an additional 28 months, 3 had a sustained antiviral response and had no evidence of hepatocellular carcinoma (HCC). Of the 6 animals that continued on a weekly ETV regimen for an additional 22 months, 4 exhibited serum viral DNA levels near the lower limit of detection for >2 years and had no evidence of HCC. Viral antigens and covalently closed circular DNA levels in liver samples were significantly reduced in all animals. ETV was well tolerated, and there was no evidence of resistant variants. On the basis of historical data, long-term ETV treatment appeared to significantly prolong the life of treated animals and delay the emergence of HCC.

    Title Emerging Perceptions of Facial Plastic Surgery Among Medical Students.
    Date December 2001
    Journal Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-head and Neck Surgery
    Excerpt

    OBJECTIVE: The purpose of this study was to examine the perceptions of medical students regarding facial aesthetic surgery and those specialists most likely to perform aesthetic or reconstructive facial surgery. METHODS: A survey was designed based on a review of the literature to assess the desirable characteristics and the perceived role of the facial plastic and reconstructive surgeon (FPRS). The surveys were distributed to 2 populations: medical students from 4 medical schools and members of the general public. RESULTS: A total of 339 surveys were collected, 217 from medical students and 122 from the general public. Medical students and the public had similar responses. The results demonstrated that respondents preferred a male plastic surgeon from the ages of 41 to 50 years old and would look to their family doctor for a recommendation. Facial aesthetic and reconstructive surgery was considered the domain of maxillofacial and general plastic surgeons, not the FPRS. CONCLUSION: Integration of the FPRS into the medical school curriculum may help to improve the perceived role of the specialty within the medical community. It is important for the specialty to communicate to aspiring physicians the dedicated training of an otolaryngologist specializing in FPRS.

    Title Localized Laryngotracheobronchial Amyloidosis: Case Report and Review of the Literature.
    Date October 2001
    Journal Ear, Nose, & Throat Journal
    Excerpt

    Although localized laryngotracheobronchial amyloidosis is rare, the otolaryngologist--head and neck surgeon should be familiar with this condition. Its characteristic appearance can suggest its presence in a patient who has the typical initial symptoms. Biopsies during direct laryngoscopy and bronchoscopy can play both a diagnostic and therapeutic role. After an appropriate examination to rule out systemic involvement, the patient should be managed with conservative surgery, although the use of a CO2 laser might be more efficacious than conventional surgery. With appropriate diagnosis and treatment, patients should expect a favorable prognosis. In this article, we describe a new case of localized laryngotracheobronchial amyloidosis in a 67-year-old woman, and we review the literature on this subject.

    Title The Contribution of Md-phd Training to Academic Orthopaedic Faculties.
    Date September 2001
    Journal Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society
    Excerpt

    Little is known about the distribution of research-trained physicians across the various specialties. To document the extent to which MD-PhD programs are a source of research-trained faculty for orthopaedic departments, this study examined the specialty choices of graduates of the Medical Scientist Training Program (MSTP) from 1964 to 1994. The MSTP, a combined MD-PhD program supported by the National Institute of General Medical Sciences, (NIGMS), produces roughly 25% of all MD-PhDs in the US. METHODS: Copies of the appendices from training grant applications containing information on MSTP graduates were obtained from the NIGMS. Also, a questionnaire was mailed to 116 university-affiliated orthopaedic surgery departments asking how many faculty were MD's, PhDs or MD-PhDs. RESULTS: Records were obtained for all MST programs. Information on postdoctoral training and/or a current position was reported for 1615 graduates who earned both MD and PhD. Of these graduates, 277 chose non-clinical paths. The other 1338 entered a residency or internship. Of these, 593 were still in residency training, 566 were academic faculty members and 130 were in private practice. In the records, 12 (0.9%) were listed as orthopaedic surgical residents (6) or faculty (6). At this time, all 12 have completed training, and 11 are in academic practice. Eighty-three departments replied to the questionnaire. In that sample of 1761 faculty positions, 1478 were MDs, 217 were PhDs and 36 (2.0%) were MD-PhDs. CONCLUSION: Despite robust support of MD-PhD programs, the number of dual degree recipients on orthopaedic faculties is small when compared to the relative size of the specialty. Other sources of research-trained staff should perhaps be developed.

    Title A Preliminary Study of Joint Surface Changes After an Intraarticular Fracture: a Sheep Model of a Tibia Fracture with Weight Bearing After Internal Fixation.
    Date August 2001
    Journal Journal of Orthopaedic Trauma
    Excerpt

    OBJECTIVE: To evaluate the changes in the articular cartilage and subchondral bone after an osteotomy designed to simulate an articular fracture. DESIGN: The contribution of the cartilage and subchondral bone was evaluated twelve weeks after creating a 1.0-millimeter step-off in the medial plateau of the tibia of twelve adult domestic sheep. All animals surviving were labeled with fluorescent markers for bone production, oxytetracycline (fifty milligrams per kilogram), and calcein (twelve milligrams per kilogram) nine and 11.5 weeks after surgery. The knees were loaded in compression using an Instron materials tester with pressure-sensitive film to record joint contact pressures above and below the medial meniscus. SETTING: The studies were performed in the research laboratories of the Orthopaedic Laboratory at Harborview Medical Center in Seattle, Washington and the Madigan Army Medical Center in Tacoma, Washington. ANIMALS: Twelve adult domestic sheep. INTERVENTION: An intraarticular osteotomy of the medial tibial plateau with 1.0 millimeter of displacement was performed. The osteotomy was stabilized with 3.5-millimeter lag screws. MAIN OUTCOME MEASURES: The contact pressures of the knee joint and articular histology were evaluated twelve weeks after surgery. Samples of the articular cartilage were analyzed by light microscopy and electron microscopy to evaluate the response of the articular cartilage and subchondral bone of the differential joint loading because of the irregularity in the articular surface caused by the osteotomy. RESULTS: The knees with an intraarticular step-off had two major contact areas with an intervening zone of reduced load corresponding to the edge of the depressed fragment. Coronal histologic sections through the articular surface showed the presence of thinning and fibrillation on the high side of the step-off and some compensatory hypertrophy of the cartilage. The subchondral bone was not responsible for restoring articular congruity because the rate of bone production was similar between the low side of the articular fracture (1.85 micrometers per day) and the high side of the fracture (1.67 micrometers per day). Scanning electron microscopy showed partial cartilage remodeling by deformation of the high side cartilage with bending of the vertical collagen fibrils, even in the unloaded state. CONCLUSIONS: In this model with a small fracture displacement (1.0 millimeter), which was less than the thickness of the articular cartilage (1.5 millimeters), the contour of the joint improved despite residual articular surface incongruency after the fracture healing.

    Title Alberto Facundo Borges, Md.
    Date July 2001
    Journal Archives of Facial Plastic Surgery : Official Publication for the American Academy of Facial Plastic and Reconstructive Surgery, Inc. and the International Federation of Facial Plastic Surgery Societies
    Title Prolonged Exposure of T Cells to Tnf Down-regulates Tcr Zeta and Expression of the Tcr/cd3 Complex at the Cell Surface.
    Date July 2001
    Journal Journal of Immunology (baltimore, Md. : 1950)
    Excerpt

    A role for TNF-alpha in the pathogenesis of chronic inflammatory disease is now firmly established. Paradoxically, TNF also has potent immunomodulatory effects on CD4(+) T lymphocytes, because Ag-specific proliferative and cytokine responses are suppressed following prolonged exposure to TNF. We explored whether TNF attenuated T cell activation by uncoupling proximal TCR signal transduction pathways using a mouse T cell hybridoma model. Chronic TNF exposure induced profound, but reversible, T cell hyporesponsiveness, with TNF-treated T cells requiring TCR engagement with higher peptide concentrations for longer periods of time for commitment to IL-2 production. Subsequent experiments revealed that chronic TNF exposure led to a reversible loss of TCRzeta chain expression, in part through a reduction in gene transcription. Down-regulation of TCRzeta expression impaired TCR/CD3 assembly and expression at the cell surface and uncoupled membrane-proximal tyrosine phosphorylation events, including phosphorylation of the TCRzeta chain itself, CD3epsilon, ZAP-70 protein tyrosine kinase, and linker for activation of T cells (LAT). Intracellular Ca(2+) mobilization was also suppressed in TNF-treated T cells. We propose that TNF may contribute to T cell hyporesponsiveness in chronic inflammatory and infectious diseases by mechanisms that include down-regulation of TCRzeta expression. We speculate that by uncoupling proximal TCR signals TNF could also interrupt mechanisms of peripheral tolerance that are dependent upon intact TCR signal transduction pathways.

    Title Crystal Structure of Human Cathepsin V.
    Date December 2000
    Journal Biochemistry
    Excerpt

    Cathepsin V is a lysosomal cysteine protease that is expressed in the thymus, testis and corneal epithelium. We have determined the 1.6 A resolution crystal structure of human cathepsin V associated with an irreversible vinyl sulfone inhibitor. The fold of this enzyme is similar to the fold adopted by other members of the papain superfamily of cysteine proteases. This study provides a framework for understanding the structural basis for cathepsin V's activity and will aid in the design of inhibitors of this enzyme. A comparison of cathepsin V's active site with the active sites of related proteases revealed a number of differences, especially in the S2 and S3 subsites, that could be exploited in identifying specific cathepsin V inhibitors or in identifying inhibitors of other cysteine proteases that would be selective against cathepsin V.

    Title An Animal Model for the Study of Genetic Predisposition in the Pathogenesis of Middle Ear Inflammation.
    Date October 2000
    Journal The Laryngoscope
    Excerpt

    OBJECTIVES: Chronic otitis media with effusion (COME) is the most prevalent inflammatory disease in children and is associated with numerous adverse long-term sequelae. Many factors have been associated with an increased risk of developing COME, one of which may be a genetic predisposition to the disease. To study the role that genetics play in the pathogenesis of COME, we used an animal model to compare the middle ear inflammatory responses in two different strains of rats (Lewis and Fisher). METHODS: In earlier studies, we demonstrated that exposure of the middle ear to endotoxin caused early extensive exudation and, later, goblet cell hyperplasia and mucin hypersecretion. In the present study, the animals were divided into six groups. In each group the animals were given transtympanic injection with gram-positive bacterial cell wall product (peptidoglycan-polysaccharide [PG-PS]). The middle ear bullae were studied at 1 week and 3 weeks after infection, and after systemic reinfection. Comparisons were made of the quantity of mucin exudate by enzyme-linked immunosorbent assay and by histological evaluation of the middle ear epithelial thickness. RESULTS: Our data demonstrate a statistically significant difference in middle ear inflammation and effusion formation between the two genetically different strains of rats. CONCLUSIONS: These data support the hypothesis that the middle ear response to PG-PS may be genetically determined and therefore suggest that genetic predisposition may play a role in the pathogenesis of COME.

    Title A Novel Approach to Serine Protease Inhibition: Kinetic Characterization of Inhibitors Whose Potencies and Selectivities Are Dramatically Enhanced by Zinc(ii).
    Date May 2000
    Journal Biochemistry
    Excerpt

    Serine proteases play a role in a variety of disease states and thus are attractive targets for therapeutic intervention. We report the kinetic characterization of a class of serine protease inhibitors whose potencies and selectivities are dramatically enhanced in the presence of Zn(II). The structural basis for Zn(II)-mediated inhibition of trypsin-like proteases has recently been reported [Katz, B. A., Clark, J. M., Finer-Moore, J. S., Jenkins, T. E., Johnson, C. R., Ross, M. J., Luong, C., Moore, W. R., and Stroud, R. M. (1998) Nature 391, 608-612]. A case study of the kinetic behavior of human tryptase inhibitors is provided to illustrate the general phenomenon of Zn(II)-mediated inhibition. Tryptase, Zn(II), and the inhibitor form a ternary complex which exhibits classic tight-binding inhibition. The half-life for release of inhibitor from the tryptase-Zn(II)-inhibitor complex has been measured for a number of inhibitors. Consistent with tight-binding behavior, potent tryptase inhibitors are characterized by extremely slow rates of dissociation from the ternary complex with half-lives on the order of hours. A model of human serum, designed to reproduce physiological levels of Zn(II), has been employed to evaluate the performance of Zn(II)-potentiated tryptase inhibitors under physiological conditions. We demonstrate that Zn(II)-mediated inhibition can be achieved at physiological Zn(II) levels.

    Title Community Health Survey in an Urban African-american Neighborhood: Distribution and Correlates of Elevated Blood Pressure.
    Date May 2000
    Journal Ethnicity & Disease
    Excerpt

    While considerable improvements have been made over the last 30 years in hypertension (HTN) awareness, treatment, and control, a recent reversal of these trends has been documented with African-American adults, particularly among those continuing to suffer from uncontrolled hypertension and its adverse consequences. This paper presents data from a cross-sectional representative survey of the health status of an urban African-American community. The study was designed in partnership with community leadership to improve HTN care and control. The baseline survey was a face-to-face interview (including blood pressure [BP] measurements) of 2,196 adults residing in randomly selected blocks in the Sandtown-Winchester neighborhood in Baltimore City. These sample data were compared with national data from the NHANES III survey, and demonstrated similar awareness of hypertension. However, hypertension control rates among treated hypertensives were significantly lower in the study community (28%) than in the national survey (44%). Compared with normotensive individuals, those with HTN were significantly older, had less education, were less likely to be employed, and had lower annual incomes. Individuals with HTN were also significantly more likely to rate their health as poor/fair, to report a history of heart disease, stroke, diabetes, kidney disease, obesity, high cholesterol, and lack of exercise, as well as to be at greater risk of alcoholism or alcohol problems. Hypertensive individuals (88% with reported prior history, 12% newly detected) were significantly more likely to have a usual source of care, have seen a health professional in the last 12 months, and to be extremely satisfied with the provider; however, 20% of individuals with hypertension reported no health insurance. These data indicate the need for focused interventions to enhance hypertension maintenance of care and adherence to treatment.

    Title Lens Cytoskeleton and Transparency: a Model.
    Date January 2000
    Journal Eye (london, England)
    Excerpt

    The function of the cytoskeleton in lens was first considered when cytoplasmic microtubules were observed in elongating fibre cells of the chick lens nearly 40 years ago. Since that time, tubulin, actin, vimentin and intermediate filaments have been identified and found to function in mitosis, motility and cellular morphology during lens cell differentiation. A role for the cytoskeleton in accommodation has been proposed and modification of the cytoskeletal proteins has been observed in several cataract models. Recently, a progressive increase in protein aggregation and lens opacification was found to correspond with the loss of cytoskeletal protein in the selenite model for cataract. In the present report a model is proposed for the role of tubulin, actin, vimentin, spectrin and the lens-specific filaments, filensin and CP49, in the establishment and maintenance of transparent lens cell structure.

    Title Lens Cytoplasmic Phase Separation.
    Date December 1999
    Journal International Review of Cytology
    Excerpt

    Cytoplasmic transparency is a unique feature of lens cells. The cytoplasm is a concentrated solution of crystallin proteins with minor constituents that include cytoskeletal proteins and lens specific intermediate filaments. Under normal physiological conditions, the proteins exist as a single transparent phase. With normal aging, progressive modification of the interactions between lens proteins occurs so that conditions within the lens become favorable for phase separation. These conditions produce intracellular inhomogeneities that approach or exceed the dimensions of the wavelength of visible light (400 to 700 nm) and light scattering from lens cells increases. The resulting opacification is the primary factor in the visual loss experienced in cataract, the leading cause of blindness in the world. We study biochemical factors that regulate the cytoplasmic phase separation and maintain normal cellular transparency.

    Title Systemic Reactivation of Otitis Media with Effusion in a Rat Model.
    Date August 1999
    Journal Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-head and Neck Surgery
    Excerpt

    OBJECTIVE: This study addresses the interaction of bacterial antigens, specifically peptidoglycan-polysaccharide (PG-PS) and lipopolysaccharide (LPS), in the induction and reactivation of mucoid middle ear effusions. METHODS: Twenty-seven rats underwent eustachian tube obstruction before inoculation of the middle ear bulla with PG-PS. Three weeks later, after resolution of all middle ear effusions, 6 rats were randomly selected and euthanized as the first control group (control I). The remaining 21 animals were randomly assigned to 3 groups that received intravenous injections of Krebs Ringer (control II), PG-PS, and LPS, respectively. These rats were euthanized 2 days after intravenous injection. Middle ear mucin production and histologic changes were measured in all animals. RESULTS: The mean concentrations of mucin were 0.94 +/- 0.52 mg/mL, 0.41 +/- 0.87 mg/mL, 16.33 +/- 3.67 mg/mL, and 1.15 +/- 0.41 mg/mL in the control I, control II, PG-PS, and LPS groups, respectively. Thus the mean concentration of mucin in the middle ear lavage samples was significantly greater in rats that were injected intravenously with PG-PS than in rats in other groups (P < 0.05). Histologic analyses demonstrated a greater degree of goblet cell hyperplasia in the PG-PS group than in other groups. CONCLUSIONS: This is the first animal model of recurring otitis media with effusion in which a systemic injection of PG-PS was used to reactivate a middle ear effusion in rats previously primed with a transtympanic injection of PG-PS. This study suggests that after otitis media with effusion has resolved, it may be reactivated by the presence of bacterial antigens and/or cytokines in the systemic circulation.

    Title Polyisoprenyl Phosphate (pipp) Signaling Regulates Phospholipase D Activity: a 'stop' Signaling Switch for Aspirin-triggered Lipoxin A4.
    Date May 1999
    Journal The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology
    Excerpt

    It is of wide interest to understand how opposing extracellular signals (positive or negative) are translated into intracellular signaling events. Receptor-ligand interactions initiate the generation of bioactive lipids by human neutrophils (PMN), which serve as signals to orchestrate cellular responses important in host defense and inflammation. We recently identified a novel polyisoprenyl phosphate (PIPP) signaling pathway and found that one of its components, presqualene diphosphate (PSDP), is a potent negative intracellular signal in PMN that regulates superoxide anion generation by several stimuli, including phosphatidic acid. We determined intracellular PIPP signaling by autocoids with opposing actions on PMN: leukotriene B4 (LTB4), a potent chemoattractant, and lipoxin A4 (LXA4), a 'stop signal' for recruitment. LTB4 receptor activation initiated a rapid decrease in PSDP levels concurrent with activation of PLD and cellular responses. In sharp contrast, activation of the LXA4 receptor reversed LTB4-initiated PSDP remodeling, leading to an accumulation of PSDP and potent inhibition of both PLD and superoxide anion generation. Thus, an inverse relationship was established for PSDP levels and PLD activity with two PMN ligands that evoke opposing responses. In addition, PSDP directly inhibited both isolated human recombinant (Ki = 6 nM) and plant (Ki = 20 nM) PLD. Together, these findings link PIPP remodeling to intracellular regulation of PMN function and suggest a role for PIPPs as lipid repressors in signal transduction, a novel mechanism that may also explain aspirin's suppressive actions in vivo in cell signaling.

    Title Disruption of the Sparc Locus in Mice Alters the Differentiation of Lenticular Epithelial Cells and Leads to Cataract Formation.
    Date April 1999
    Journal Experimental Eye Research
    Excerpt

    SPARC (secreted protein acidic and rich in cysteine) is a matricellular protein that regulates cellular adhesion and proliferation. In this report, we show that SPARC protein is restricted to epithelial cells of the murine lens and ends abruptly at the equatorial bow region where lens fiber differentiation begins. SPARC protein was not detected in the lens capsule or in differentiated lens fibers. SPARC-null mice developed cataracts at approximately 3-4 months after birth, at which time posterior subcapsular opacities were observed by slit lamp ophthalmoscopy. Histological analyses of ocular sections from 3-month old animals revealed several microscopic abnormalities present in the SPARC-null mice but absent from the wild-type animals. Fiber cell elongation was incomplete posteriorly and resulted in displacement of the lenticular nucleus to the posterior of the lens. Nuclear debris was present in the posterior subcapsular region of the lens, an indication of the abnormal migration and elongation of either fetal or anterior epithelial cells, and the bow region was disrupted and vacuolated. In the anterior lens, the capsule appeared to be thickened and was lined by atypical, plump cuboidal epithelium. Moreover, anterior cortical fibers were swollen. Polyacrylamide gel electrophoresis of the epithelial, cortical and nuclear fractions of wild-type and SPARC-null lenses indicated no significant differences among the alpha-, beta-, and gamma-crystallins. Expression of alphaB-crystallin appeared similar in fiber cells of wild-type and SPARC-null lenses, although the distribution of alphaB-crystallin was asymmetric in SPARC-null lenses as a result of abnormal lens fiber differentiation. No evidence of atypical extracellular matrix deposition in areas other than the capsule was detected in wild-type or SPARC-null lens at 3 months of age. We conclude that the disruption of the Sparc locus in mice results in the alteration of two fundamental processes of lens development: differentiation of epithelial cells and maturation of fiber cells.

    Title Effects of Prolonged Oxygen Exposure at 1.5, 2.0, or 2.5 Ata on Pulmonary Function in Men (predictive Studies V).
    Date March 1999
    Journal Journal of Applied Physiology (bethesda, Md. : 1985)
    Excerpt

    As part of a study of human organ O2 tolerance, lung flow-volume and spirometric measurements were performed repeatedly before, during, and after continuous O2 exposures at 1.5, 2.0, and 2.5 ATA for average durations of 17.7, 9.0, and 5.7 h, respectively (effects of O2 breathing at 3.0 ATA for 3.5 h were reported previously; J. M. Clark, R. M. Jackson, C. J. Lambertsen, R. Gelfand, W. D. B. Hiller, and M. Unger. J. Appl. Physiol. 71: 878-885, 1991). Additional measurements of pulmonary mechanical function, gas exchange, and alveolar inflammatory cells were obtained before and after O2 exposure. Rates of pulmonary symptom development and lung volume reduction increased progressively with elevation of O2 pressure. Average rates of vital capacity reduction over a useful range of O2 pressures provided a valuable general description of pulmonary O2 tolerance in humans. However, the existence of multiple pulmonary effects of O2 toxicity and the complexity of their interactions require awareness that deviations from the average relationships may occur in different individuals or under varying conditions of O2 exposure and subsequent recovery. The associated pulmonary function deficits may represent responses to a composite of direct and indirect effects of O2 poisoning, along with related consequences and subsequent reactions to those effects.

    Title Delayed Complications of Nonoperative Management of Blunt Adult Splenic Trauma.
    Date July 1998
    Journal Archives of Surgery (chicago, Ill. : 1960)
    Excerpt

    OBJECTIVE: To determine the incidence and type of delayed complications from nonoperative management of adult splenic injury. DESIGN: Retrospective medical record review. SETTING: University teaching hospital, level I trauma center. PATIENTS: Two hundred eighty patients were admitted to the adult trauma service with blunt splenic injury during a 4-year period. Men constituted 66% of the population. The mean (+/-SEM) age was 32.2+/-1.0 years and the mean (+/-SEM) Injury Severity Score was 22.8+/-0.9. Fifty-nine patients (21%) died of multiple injuries within 48 hours and were eliminated from the study. One hundred thirty-four patients (48%) were treated operatively within the first 48 hours after injury and 87 patients (31%) were managed nonoperatively. MAIN OUTCOME MEASURES: We reviewed the number of units of blood transfused, intensive care unit length of stay, overall length of stay, outcome, and complications occurring more than 48 hours after injury directly attributable to the splenic injury. RESULTS: Patients managed nonoperatively had a significantly lower Injury Severity Score (P<.05) than patients treated operatively. Length of stay was significantly decreased in both the number of intensive care unit days as well as total length of stay (P<.05). The number of units of blood transfused was also significantly decreased in patients managed nonoperatively (P<.05). Seven patients (8%) managed nonoperatively developed delayed complications requiring intervention. Five patients had overt bleeding that occurred at 4 days (3 patients), 6 days (1 patient), and 8 days (1 patient) after injury. Three patients underwent splenectomy, 1 had a splenic artery pseudoaneurysm embolization, and 1 had 2 areas of bleeding embolization. Two patients developed splenic abscesses at approximately 1 month after injury; both were treated by splenectomy. CONCLUSION: Significant numbers of delayed splenic complications do occur with nonoperative management of splenic injuries and are potentially life-threatening.

    Title Transcatheter Fenestration of Hemi-fontan Baffles After Completion of Fontan Physiology Using Balloon Dilatation and Stent Placement.
    Date May 1998
    Journal Catheterization and Cardiovascular Diagnosis
    Excerpt

    De novo transcatheter fenestration of hemi-Fontan baffles has not been previously described. The purpose of this report is to present our experience in such de novo transcatheter fenestration in two consecutive patients with absent fenestration in whom the hemi-Fontan baffle was the only direct access to the pulmonary venous atrium.

    Title Hypoxic Ventilatory Sensitivity in Men is Not Reduced by Prolonged Hyperoxia (predictive Studies V and Vi).
    Date March 1998
    Journal Journal of Applied Physiology (bethesda, Md. : 1985)
    Excerpt

    Potential adverse effects on the O2-sensing function of the carotid body when its cells are exposed to toxic O2 pressures were assessed during investigations of human organ tolerance to prolonged continuous and intermittent hyperoxia (Predictive Studies V and VI). Isocapnic hypoxic ventilatory responses (HVR) were determined at 1.0 ATA before and after severe hyperoxic exposures: 1) continuous O2 breathing at 1.5, 2.0, and 2.5 ATA for 17.7, 9.0, and 5.7 h and 2) intermittent O2 breathing at 2.0 ATA (30 min O2-30 min normoxia) for 14.3 O2 h within 30-h total time. Postexposure curvature of HVR hyperbolas was not reduced compared with preexposure controls. The hyperbolas were temporarily elevated to higher ventilations than controls due to increments in respiratory frequency that were proportional to O2 exposure time, not O2 pressure. In humans, prolonged hyperoxia does not attenuate the hypoxia-sensing function of the peripheral chemoreceptors, even after exposures that approach limits of human pulmonary and central nervous system O2 tolerance. Current applications of hyperoxia in hyperbaric O2 therapy and in subsea- and aerospace-related operations are guided by and are well within these exposure limits.

    Title Design of Potent Selective Zinc-mediated Serine Protease Inhibitors.
    Date March 1998
    Journal Nature
    Excerpt

    Many serine proteases are targets for therapeutic intervention because they often play key roles in disease. Small molecule inhibitors of serine proteases with high affinity are especially interesting as they could be used as scaffolds from which to develop drugs selective for protease targets. One such inhibitor is bis(5-amidino-2-benzimidazolyl)methane (BABIM), standing out as the best inhibitor of trypsin (by a factor of over 100) in a series of over 60 relatively closely related analogues. By probing the structural basis of inhibition, we discovered, using crystallographic methods, a new mode of high-affinity binding in which a Zn2+ ion is tetrahedrally coordinated between two chelating nitrogens of BABIM and two active site residues, His57 and Ser 195. Zn2+, at subphysiological levels, enhances inhibition by over 10(3)-fold. The distinct Zn2+ coordination geometry implies a strong dependence of affinity on substituents. This unique structural paradigm has enabled development of potent, highly selective, Zn2+-dependent inhibitors of several therapeutically important serine proteases, using a physiologically ubiquitous metal ion.

    Title Alcohol and Drug Use in Adult Patients with Musculoskeletal Injuries.
    Date December 1997
    Journal American Journal of Orthopedics (belle Mead, N.j.)
    Excerpt

    This study reviewed trauma registry data for information on the prevalence of alcohol and drug use in adult patients with fractures and dislocations admitted to Hermann Hospital, Houston, Texas, from January 1992 to December 1994. Of the 1776 adult patients aged 18 years or older, 1126 (63%) were tested for blood alcohol concentration, and 873 (49%) had their urine screened for a panel of 58 drugs. Of the patients tested, 467 (41%) had positive blood alcohol concentrations, and 335 (30%) were legally intoxicated (blood alcohol concentration > or = 0.10%). Of the patients providing urine specimens, 191 (22%) had samples that were positive for one or more drugs. Overall, 9% of the patients tested were positive for both alcohol and drugs, and 54% were positive for either alcohol or drugs. The highest prevalence of alcohol use was in patients aged 21 to 33 years, and men were intoxicated more often than women. Alcohol use was more commonly associated with motor vehicle accidents, pedestrian or bicycle accidents, and gunshot wounds; intoxification was associated with a higher incidence of tibia fractures. The average injury severity score was higher, the duration of stay was longer, and total hospital charges were higher for the alcohol-positive group. Patients testing positive for alcohol or drugs were more likely to lack insurance coverage.

    Title Production of Crystallizable Human Chymase from a Bacillus Subtilis System.
    Date October 1997
    Journal Febs Letters
    Excerpt

    A Bacillus subtilis strain deficient in seven extracellular proteases was used to produce human mast cell chymase and is a viable expression system for serine proteases and other classes of proteins. Chymase is produced at 0.3-0.5 mg/l and is purified by three chromatography steps. Two crystal forms of PMSF-treated chymase were optimized. The first is C2 with a=47.94 A, b=85.23 A, c=174.18 A, beta=96.74 degrees, and diffracts to at least 2.1 A, while the second is P212121, with cell dimensions a=43.93 A, b=58.16 A, and c=86.09 A, and a diffraction limit of approximately 1.9 A. The first crystal form has either three or four molecules/asymmetric unit, while the second has one molecule/asymmetric unit.

    Title Protein Changes During Aging and the Effects of Long-term Cortisol Treatment in Macaque Monkey Lens.
    Date August 1997
    Journal Optometry and Vision Science : Official Publication of the American Academy of Optometry
    Excerpt

    Macaca nemestrina pig-tail macaques were administered daily oral doses of 3.85 or 5.78 mg/kg of cortisol for 1 year. The ages of the macaques were from 19 to 29 years. After 1 year, lenses were observed using a slitlamp ophthalmoscope and the stage of cataract was classified in each eye. Enucleated lenses were analyzed for content of soluble and insoluble proteins. Lens proteins were analyzed using SDS polyacrylamide gel electrophoresis (SDS-PAGE) and the changes in lens proteins were quantified using densitometry of the individual gels. Untreated control lenses were obtained over the range of 4 to 29 years of age and the proteins were analyzed. A slow progressive increase in the cataract stage and in the proportion of insoluble protein aggregates corresponded with the animal age, not the cortisol treatment. The observed changes in the protein components may suggest an important role for cytoskeletal proteins in lens transparency during aging. Exposure to high doses of oral steroids over a period of 1 year did not result in detectable modification of crystallin or cytoskeletal proteins. Even at high doses, longer exposure may be necessary to produce the cataract associated with steroid administration.

    Title Scanning Electron Microscopy of "fibrillated" and "malacic" Human Articular Cartilage: Technical Considerations.
    Date August 1997
    Journal Microscopy Research and Technique
    Excerpt

    Specimens of articular cartilage from human knees with gross evidence of malacia (dull appearance and/or softness) or fibrillation (exposed fibrous strands and/or staining with India ink) were prepared for scanning electron microscopy (SEM) and compared to cartilage from apparently intact regions. Vertical cryofractures were made through the center of each specimen, so the matrix collagen structure and its relationship to surface features could be examined. Soft, dull, malacic cartilage was characterized by the presence of numerous clefts among the collagen fibers within the most superficial region of the cartilage. In one form of this condition, these clefts did not extend through the articular surface. In a second form, usually observed where the tangential zone was normally thin or absent, the free ends of radial collagen fibers were exposed, but the deeper layers were intact. Two forms of fibrillation were also identified. The first is created by separation of the superficial lamellae which curl up from the tangential layer and form frondlike projections above the normal plane of the joint surface. In the second, deep radial fibers are exposed by vertical fissures. This second form is associated with advanced damage to the joint. The early stages of cartilage failure are characterized by debonding among the major collagen fiber tracts. This process may initiate in the deep tangential zone where the radial fibers cross into the surface. The patterns of the degenerative changes are dictated by the original architecture of the collagen matrix. The microscopic findings do not correlate adequately with conventional gross grading. SEM provides useful information about injured articular cartilage.

    Title Relationship of 133xe Cerebral Blood Flow to Middle Cerebral Arterial Flow Velocity in Men at Rest.
    Date December 1996
    Journal Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
    Excerpt

    Cerebral blood flow (CBF) was measured by 133Xe clearance simultaneously with the velocity of blood flow through the left middle cerebral artery (MCA) over a wide range of arterial PCO2 in eight normal men. Average arterial PCO2, which was varied by giving 4% and 6% CO2 in O2 and by controlled hyperventilation on O2, ranged from 25.3 to 49.9 mm Hg. Corresponding average values of global CBF15 were 27.2 and 65.0 ml 100 g min-1, respectively, whereas MCA blood-flow velocity ranged from 42.8 to 94.2 cm/s. The relationship of CBF to MCA blood-flow velocity over the imposed range of arterial PCO2 was described analytically by a parabola with the equation: CBF = 22.8 - 0.17 x velocity + 0.006 x velocity2 The observed data indicate that MCA blood-flow velocity is a useful index of CBF response to change in arterial PCO2 during O2 breathing at rest. With respect to baseline values measured while breathing 100% O2 spontaneously, percent changes in velocity were significantly smaller than corresponding percent changes in CBF at increased levels of arterial PCO2 and larger than CBF changes at the lower arterial PCO2. These observed relative changes are consistent with MCA vasodilation at the site of measurement during exposure to progressive hypercapnia and also during extreme hyperventilation hypocapnia.

    Title Cognitive Components of Picture Naming.
    Date September 1996
    Journal Psychological Bulletin
    Excerpt

    A substantial research literature documents the effects of diverse item attributes, task conditions, and participant characteristics on the case of picture naming. The authors review what the research has revealed about 3 generally accepted stages of naming a pictured object: object identification, name activation, and response generation. They also show that dual coding theory gives a coherent and plausible account of these findings without positing amodal conceptual representations, and they identify issues and methods that may further advance the understanding of picture naming and related cognitive tasks.

    Title Transferrin Receptor Expression in Nonsmall Cell Lung Cancer. Histopathologic and Clinical Correlates.
    Date June 1996
    Journal Cancer
    Excerpt

    BACKGROUND. In the search for tumor-related antigens with survival-predictive value, previous studies have yielded varied conclusions regarding the expression of one such antigen, the transferrin receptor in lung cancer. The goal of this study was to define the frequency of expression of transferrin receptor in lung cancer specimens and gather preliminary data regarding the prognostic value of this tumor-related antigen. METHODS. Tissue immunoreactivity was studied with a murine monoclonal antibody to transferrin receptor in patients with nonsmall cell lung cancer who underwent surgical resection at the Medical Center Hospital of Vermont during the period from January, 1988, to May, 1991. RESULTS. The study group consisted of 32 patients (21 males and 11 females) with an average follow-up length of 27 months (standard deviation of 16 months). There were 17 patients with adenocarcinoma, 14 with squamous cell carcinoma, and 1 with large cell carcinoma. At the end of data accumulation, a total of 16 deaths had been recorded (8 with squamous cell, 8 with adenocarcinoma). Normal lung tissue did not stain for transferrin receptor; however, 13 of 17 (76%) adenocarcinomas, 13 of 14 (93%) squamous cell carcinomas, and the 1 large cell carcinoma stained positively for transferrin receptor. Staining for transferrin receptor was graded according to pattern and intensity and categorized as absent-weak or strong. Survival analysis was performed to evaluate patient outcome based on a variety of clinical and experimentally determined characteristics. Groups based on N-status (N0 vs. N1 + N2, P = 0.08), stage (Stage 1 vs. Stage 2 + 3 P = 0.13), age (younger than 60 vs. 60 years or older, P = 0.09), and transferrin receptor staining (absent-weak vs. strong, P = 0.14) achieved nearly significant differences in survival. Further analysis of the differences in survival for groupings based on transferrin receptor staining found that these differences in survival reached significance for patients with larger tumors (T2 or T3, P = 0.02). CONCLUSIONS. Transferrin receptor is expressed in the majority of lung cancers and the presence of transferrin receptor in nonsmall cell lung cancers may be an indicator of poorer prognosis in certain groups of patients.

    Title Melas: Clinical and Pathologic Correlations with Mri, Xenon/ct, and Mr Spectroscopy.
    Date February 1996
    Journal Neurology
    Excerpt

    We describe the clinical, imaging, and pathologic findings in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). The patient experienced her first stroke-like episode at age forty-four. Brain MRI, obtained at symptom onset, at 3 weeks, and at 1 year, revealed migrating T2-weighted hyperintensities in the temporal/parietal and occipital cortices and later revealed atrophy. Abnormal cerebrovascular reserve was evident on xenon/CT four days after the first MRI. MR spectroscopy at 1 year revealed increased lactate in both the occipital and temporal lobes. Histologic sections demonstrated spongy degeneration of the cortex that was most prominent at the crests of the gyri. Electron microscopy of the blood vessels showed increased numbers of abnormal mitochondria within the vascular smooth muscle and in endothelial cells. We hypothesize that the stroke-like episodes in MELAS may be due to impaired autoregulation secondary to the impaired metabolic activity of mitochondria in the endothelial and smooth muscle cells of blood vessels.

    Title Tryptase Inhibitors Block Allergen-induced Airway and Inflammatory Responses in Allergic Sheep.
    Date January 1996
    Journal American Journal of Respiratory and Critical Care Medicine
    Excerpt

    Tryptase, a mast cell serine protease, has been implicated in the pathophysiology of allergic asthma, but formal evidence to support this hypothesis has been limited by the lack of specific inhibitors for use in vivo. Therefore, in this study we examined the effects of two inhibitors of tryptase, APC 366 [N-(1-hydroxy-2-naphthoyl)-L-arginyl-L-prolinamide hydrochloride] and BABIM [bis(5-amidino-2-benzimidazolyl)methane] on antigen-induced early and late responses, airway responsiveness as measured by carbachol provocation, microvascular permeability as measured by bronchoalveolar lavage (BAL) albumin concentrations, and tissue eosinophilia from biopsies in allergic sheep. APC 366 and BABIM were administered by aerosol in all experiments. In vehicle control trials, antigen challenge resulted in peak early and late increases in specific lung resistance (SRL) of (mean +/- SE, n = 6) 259 +/- 30% and 183 +/- 27% over baseline, respectively. Treatment with APC 366 (9 mg/3 ml H2O given 0.5 h before, 4 h after, and 24 h after antigen challenge) slightly reduced the peak early response (194 +/- 41%), but significantly inhibited the late response (38 +/- 6%, p < 0.05 versus control trials). Twenty-four hours after challenge, APC 366 also completely blocked the antigen-induced airway hyperresponsiveness to inhaled carbachol observed in the control trial.(ABSTRACT TRUNCATED AT 250 WORDS)

    Title Ph Testing of Feeding-tube Aspirates to Determine Placement.
    Date November 1995
    Journal Nutrition in Clinical Practice : Official Publication of the American Society for Parenteral and Enteral Nutrition
    Excerpt

    Although radiologic confirmation of tube placement remains the "gold standard," there is growing evidence that pH testing of feeding-tube aspirates can reduce (although not totally eliminate) reliance on x-rays used for this purpose. This article describes that evidence and tells how it was obtained. Reducing the number of x-rays needed to confirm tube position can have far-reaching financial benefits.

    Title Vertical Gaze Palsies from Medial Thalamic Infarctions Without Midbrain Involvement.
    Date September 1995
    Journal Stroke; a Journal of Cerebral Circulation
    Excerpt

    BACKGROUND: Although the supranuclear pathways for vertical gaze control are not well defined, lesions of the mesencephalic reticular formation including the nucleus of Darkschewitsch, the rostral interstitial medial longitudinal fasciculus, the interstitial nucleus of Cajal, and the posterior commissure are known to produce vertical gaze palsies. MRI studies have not previously reported isolated thalamic lesions as the cause of vertical gaze palsies. CASE DESCRIPTIONS: Three patients with acute paralysis of vertical gaze were imaged with MRI. Sagittal T1 and axial T1, T2, and proton-weighted images were obtained. All three patients had repeated scans performed from 3 days to 6 weeks after the original study. Two patients exhibited unilateral right thalamic infarcts (polar and paramedial territory), and one patient had a bilateral paramedian thalamic infarction. There was no evidence of midbrain involvement on any of the images. CONCLUSIONS: Vertical gaze palsies are known to be produced by lesions of the rostral interstitial medial longitudinal fasciculus. This MRI study reveals thalamic infarctions without associated midbrain infarctions in three patients with vertical gaze palsies. This may be explained by interruption of supranuclear inputs.

    Title Mast Cell Tryptase: a New Target for Therapeutic Intervention in Asthma.
    Date August 1995
    Journal International Archives of Allergy and Immunology
    Title Human Tolerance and Physiological Responses to Exercise While Breathing Oxygen at 2.0 Ata.
    Date July 1995
    Journal Aviation, Space, and Environmental Medicine
    Excerpt

    Multiple physiological functions were monitored in ten men who performed two 30-min periods of 150-W ergometer exercise during 120-min exposures to O2 at 2.0 ATA. There were no convulsions or electroencephalographic manifestations of increased excitability. Sequential measurements of peripheral visual fields, pulmonary mechanical function, mental performance, and cardiovascular function during the resting recovery after each of the two exercise periods were not detectably altered from pre-exercise control values. Pre- and post-exposure measurements of visual acuity, accommodation, pupil diameter, visual cortical activity, and retinal electrical activity also revealed no significant differences. While CNS symptoms were absent, average arterial PCO2 rose by about 5 mm Hg during both exercise periods. This finding was confirmed in six subjects who performed four 6-min periods of continuous exercise at 50, 100, 150, and 200 W while breathing O2 at 2.0 ATA. Average arterial PCO2 rose nearly linearly from 34.3 mm Hg at rest to 44.0 mm Hg at 200 W. Arterial PCO2-related increments in brain blood flow and PO2 may explain part or all of the known detrimental influence of exercise on CNS O2 tolerance.

    Title Quantitative Analysis of the Lens Cell Microstructure in Selenite Cataract Using a Two-dimensional Fourier Analysis.
    Date July 1995
    Journal Experimental Eye Research
    Excerpt

    Using two-dimensional (2-D) Fourier methods, we analysed the cellular microstructure of three rat lenses: normal transparent, selenite-induced cataractous and selenite-treated plus a phase separation inhibitor (PSI) to prevent cataract. 2-D Fourier analysis of electron micrographs of the lens cells quantified the dimensions of the spatial fluctuations in electron density of the lens cell microstructure. The 2-D Fourier spectra of the transparent normal and PSI-treated lens cells were remarkably similar while those of the opaque selenite-treated lens cells were dramatically different. In the opaque cells the contributions of large Fourier components (larger than half the wavelength of light) in the 2-D Fourier spectra were much greater than in the transparent cells. The results of the 2-D Fourier analysis of electron micrographs are consistent with the theory of transparency of the eye.

    Title Delayed Neuropsychologic Sequelae After Carbon Monoxide Poisoning: Prevention by Treatment with Hyperbaric Oxygen.
    Date May 1995
    Journal Annals of Emergency Medicine
    Excerpt

    STUDY OBJECTIVE: Carbon monoxide (CO) poisoning is a major clinical problem. The risk of morbidity and the most effective treatment have not been clearly established. We measured the incidence of delayed neurologic sequelae (DNS) in a group of patients acutely poisoned with CO and tested the null hypothesis that the incidence would not be affected by treatment with hyperbaric oxygen (HBO). DESIGN: We conducted a prospective, randomized study in patients with mild to moderate CO poisoning who presented within 6 hours. Patients had no history of loss of consciousness or cardiac instability. INTERVENTIONS: The incidence of DNS was compared between groups treated with ambient pressure 100% oxygen or HBO (2.8 ATA for 30 minutes followed by 2.0 ATA oxygen for 90 minutes). DNS were defined as development of new symptoms after oxygen treatment plus deterioration on one or more subtests of a standardized neuropsychologic screening battery. RESULTS: In 7 of 30 patients (23%), DNS developed after treatment with ambient-pressure oxygen, whereas no sequelae developed in 30 patients after HBO treatment (P < .05). DNS occurred 6 +/- 1 (mean +/- SE) days after poisoning and persisted 41 +/- 8 days. At follow-up 4 weeks after poisoning, patients who had been treated with ambient pressure oxygen and had not sustained DNS exhibited a worse mean score on one subtest, Trail Making, compared with the group treated with HBO and with a control group matched according to age and education level. There were no differences in scores between the control group and the hyperbaric oxygen group. CONCLUSION: DNS after CO poisoning cannot be predicted on the basis of a patient's clinical history or CO level. HBO treatment decreased the incidence of DNS after CO poisoning.

    Title Retrieval Mechanisms in the Development of Instance and Superordinate Naming of Pictures.
    Date August 1994
    Journal Journal of Experimental Child Psychology
    Excerpt

    Children's use of superordinate names lags behind their use of instance names, and production lags behind comprehension. The hypothesis that both of these developmental delays reflect underlying retrieval difficulties predicts an interaction between name generality (instance vs. superordinate) and task (comprehension vs. production). Specifically, production of superordinate names should be more difficult for children than the separate name generality and task effects would predict. To examine this hypothesis, 32 junior kindergarten and 32 Grade 1 children in Experiment 1 performed an instance and superordinate name comprehension task for 96 single-exemplar pictures from 12 categories, and 32 junior kindergarten and 32 Grade 1 children in Experiment 2 produced instance or superordinate names for the same pictures. As predicted, the combination of superordinate names and language production was particularly difficult, especially for junior kindergarten children. High rates of instance name intrusions and other findings suggest that superordinate name production may be interfered with by more readily available instance names. Weak inhibition of competing instance names and other mechanistic explanations for the effects are considered.

    Title Survey of the Anopheles Maculatus Complex (diptera: Culicidae) in Peninsular Malaysia by Analysis of Cuticular Lipids.
    Date January 1994
    Journal Journal of Medical Entomology
    Excerpt

    Anopheles maculatus Theobald sensu lato is a species complex now consisting of eight sibling species; An. maculatus is still represented by two cytologically distinct forms; i.e., the widely distributed sensu strictu or B, and E from southern Thailand and adjacent areas in northern Malaysia. Cuticular lipid profiles in conjunction with principal component analysis was used to separate An. maculatus form E from sensu stricto form B in a preliminary survey of the An. maculatus complex at five locations spanning peninsular Malaysia. The relative rank orders, from the areas of the five gas chromatographic peaks used to determine lipid differences for specimens from peninsular Malaysia, matched well with those from cytogenetically identified colony specimens of An. maculatus forms B and E. The two-dimensional principal component pattern of specimens identified as form E was highly clumped, which indicated that very similar cuticular lipids were present within this putative malaria vector. Both forms coexisted in peninsular Malaysia, but form E may be dominant except in the south.

    Title Encephalopathy Due to Severe Hyponatremia in an Ultramarathon Runner.
    Date October 1993
    Journal The Western Journal of Medicine
    Title Nosocomial Legionella Pneumonia in the Neonate.
    Date September 1993
    Journal Pediatrics
    Title The Use of Postoperative Suction Drainage in Total Hip Arthroplasty.
    Date January 1993
    Journal Orthopedics
    Excerpt

    Two hundred eight primary total hip arthroplasties were reviewed to evaluate the effect of closed suction drainage. This review included 45 hips in which closed drains were used and 163 hips in which drains were not used. These two groups were compared for possible differences in wound problems, temperature elevations, changes in Hgb/Hct, and the need for transfusions. There was no statistically significant difference in postoperative temperatures or decrease in Hgb. However, there were four superficial wound infections in the drained group and three superficial wound infections in the non-drained group (P < .025). There were no deep infections in either group. These findings suggest closed suction drainage provides no apparent advantage in uncomplicated primary total hip arthroplasty.

    Title Dynamic Heterogeneity of Cerebral Hypoperfusion After Prolonged Cardiac Arrest in Dogs Measured by the Stable Xenon/ct Technique: a Preliminary Study.
    Date May 1992
    Journal Resuscitation
    Excerpt

    After prolonged cardiac arrest and reperfusion, global cerebral blood flow (gCBF) is decreased to about 50% normal for many hours. Measurement of gCBF does not reveal regional variation of flow or permit testing of hypotheses involving multifocal no-flow or low-flow areas. We employed the noninvasive stable Xenon-enhanced Computerized Tomography (Xe/CT) local CBF (LCBF) method for use in dogs before and after ventricular fibrillation (VF) cardiac arrest of 10 min. This was followed by external cardiopulmonary resuscitation (CPR) and control of cardiovascular pulmonary variables to 7 h postarrest. In a sham (no arrest) experiment, the three CT levels studied showed normal regional heterogeneity of LCBF values, all between 10 and 75 ml/100 cm3 per min for white matter and 20 and 130 ml/100 cm3 per min for gray matter. In four preliminary CPR experiments, the expected global hyperemia at 15 min after arrest, was followed by hypoperfusion with gCBF reduced to about 50% control and increased heterogeneity of LCBF. Trickle flow areas (LCBF less than 10 ml/100 cm3 per min) not present prearrest, were interspersed among regions of low, normal, or even high flow. Regions of 125-500 mm3 with trickle flow or higher flows, in different areas at different times, involving deep and superficial structures migrated and persisted to 6 h, with gCBF remaining low. These preliminary results suggest: no initial no-reflow foci (less than 10 ml/100 cm3 per min) larger than 125 mm3 persisting through the initial global hyperemic phase; delayed multifocal hypoperfusion more severe than suggested by gCBF measurements; and trickle flow areas caused by dynamic factors.

    Title Nontraumatic Femur Fracture in an Oligomenorrheic Athlete.
    Date April 1992
    Journal Medicine and Science in Sports and Exercise
    Excerpt

    Exercise-associated amenorrhea is the cessation of menses in a woman following onset of training or an increase in training intensity. Its physiologic basis is characterized by consistently low levels of gonadotropin and ovarian hormones, but the underlying cause of this phenomenon is unknown. Although osteopenia has been described in amenorrheic women athletes, it has been primarily a laboratory diagnosis. Several recent studies have described a significantly lower bone mineral density (BMD) in the lumbar spine of amenorrheic athletes. Marcus et al. also reported an increased number of metatarsal and tibial stress fractures in a group of amenorrheic women. We report here the first case of a nontraumatic femur fracture in an amenorrheic athlete. A 32-yr-old white female, with four prior fibular stress fractures, suffered a left femoral shaft fracture during the 13th mile of a half-marathon. The fracture was successfully internally fixed. Biochemical studies showed no metabolic abnormality. Bone mineral density of the lumbar spine, femoral neck, tibia, and fibula were below the mean for both eumenorrheic and amenorrheic female athletes. Exercise-associated amenorrhea is a medical problem that may have serious implications for both competitive and high-intensity recreational female athletes.

    Title Cuticular Lipid Differences Between the Malaria Vector and Non-vector Forms of the Anopheles Maculatus Complex.
    Date February 1992
    Journal Medical and Veterinary Entomology
    Excerpt

    Two chromosomal forms (E and F) of the Anopheles maculatus Theobald complex were distinguished by gas-liquid chromatographic (GC) analysis of cuticular lipids in association with a multivariate principal component analysis. The GC chromatogram obtained from n-hexane extracts of individual specimens showed no consistent qualitative differences in normalized peak areas between forms. Of the seventeen consistent peaks, five were found to be quantitatively different between forms at a high (99.5-99.95%) level of statistical confidence. Relative ratios of these five quantitatively different GC peaks were used as criteria to distinguish single specimens as either form E or form F. Chemical structures of the five GC peaks were assigned by both electron impact and chemical ionization gas chromatography/mass spectrometry analysis. The first three peaks, which were always doublets, were partially resolved saturated and mono-unsaturated free fatty acids; the other two peaks were n-alkanes. Principal component analysis substantiated that the vector form E has very similar cuticular lipid profiles and is well separated from the non-vector form F.

    Title Pulmonary Function in Men After Oxygen Breathing at 3.0 Ata for 3.5 H.
    Date January 1992
    Journal Journal of Applied Physiology (bethesda, Md. : 1985)
    Excerpt

    As a pulmonary component of Predictive Studies V, designed to determine O2 tolerance of multiple organs and systems in humans at 3.0-1.5 ATA, pulmonary function was evaluated at 1.0 ATA in 13 healthy men before and after O2 exposure at 3.0 ATA for 3.5 h. Measurements included flow-volume loops, spirometry, and airway resistance (Raw) (n = 12); CO diffusing capacity (n = 11); closing volumes (n = 6); and air vs. HeO2 forced vital capacity maneuvers (n = 5). Chest discomfort, cough, and dyspnea were experienced during exposure in mild degree by most subjects. Mean forced expiratory volume in 1 s (FEV1) and forced expiratory flow at 25-75% of vital capacity (FEF25-75) were significantly reduced postexposure by 5.9 and 11.8%, respectively, whereas forced vital capacity was not significantly changed. The average difference in maximum midexpiratory flow rates at 50% vital capacity on air and HeO2 was significantly reduced postexposure by 18%. Raw and CO diffusing capacity were not changed postexposure. The relatively large change in FEF25-75 compared with FEV1, the reduction in density dependence of flow, and the normal Raw postexposure are all consistent with flow limitation in peripheral airways as a major cause of the observed reduction in expiratory flow. Postexposure pulmonary function changes in one subject who convulsed at 3.0 h of exposure are compared with corresponding average changes in 12 subjects who did not convulse.

    Title Response of Cortical Bone to Local Controlled Release of Sodium Fluoride: the Effect of Implant Insertion Site.
    Date November 1991
    Journal Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society
    Excerpt

    In a previous experiment, sodium fluoride in a biodegradable polymer matrix was introduced into the femoral canal of the rabbit and bone formation was compared with contralateral controls. We noted significant bone formation, but only in the distal third of the periosteal surface of the femur. This experiment was performed to distinguish fluoride-induced periosteal bone formation from that due to the reactive osteogenic changes associated with local injury caused by the process of implantation. A proximal approach on the right leg and a distal approach on the left were used for the insertion of the implants in rabbits. Femurs were removed after 30 days and tested for stiffness and load to failure. The cross-sectional area of mineralized bone was determined at proximal, midshaft, and distal locations. Fluorescent bone tissue growth labels were injected at weekly intervals to measure the rate of new periosteal bone formation. The results were compared with a control group that received sham implants. Results showed no difference between measured properties in right and left femurs in the control group or in those exposed to fluoride. A significant increase was found in the fluoride group in load to failure, along with cross-sectional area of mineralized bone, and periosteal growth rates compared with the control group, but no difference was seen in stiffness. No difference was detected between the response proximally and distally in the fluoride group regardless of the location of insertion. There were no detectable changes in serum fluoride level after implantation of the poly L-lactic acid/sodium fluoride matrix. These results show that fluoride exerts its osteogenic effects equally at proximal, midshaft, and distal regions of diaphyseal bone and is uninfluenced by the site of local injury due to insertion of the implant.

    Title Amphotericin B Lipid Complex Therapy of Experimental Fungal Infections in Mice.
    Date August 1991
    Journal Antimicrobial Agents and Chemotherapy
    Excerpt

    The amphotericin B lipid complex (ABLC), which is composed of amphotericin B and the phospholipids dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol, was evaluated for its acute toxicity in mice and for its efficacy in mice infected with a variety of fungal pathogens. ABLC was markedly less toxic to mice when it was administered intravenously; it had a 50% lethal dose of greater than 40 mg/kg compared with a 50% lethal dose of 3 mg/kg for Fungizone, the desoxycholate form of amphotericin B. ABLC was efficacious against systemic infections in mice caused by Candida albicans, Candida species other than C. albicans, Cryptococcus neoformans, and Histoplasma capsulatum. ABLC was also efficacious in immunocompromised animals infected with C. albicans, Aspergillus fumigatus, and H. capsulatum. Against some infections, the efficacy of ABLC was comparable to that of Fungizone, while against other infections Fungizone was two- to fourfold more effective than ABLC. Against several infections. Fungizone could not be given at therapeutic levels because of intravenous toxicity. ABLC, with its reduced toxicity, could be administered at drug levels capable of giving a therapeutic response. ABLC should be of value in the treatment of severe fungal infections in humans.

    Title Further Observations on the Phagocytosis of Candida Albicans by Hamster and Human Oocytes.
    Date March 1991
    Journal Molecular Reproduction and Development
    Excerpt

    Pathogenic yeast, Candida albicans, were incubated with hamster and human oocytes for up to 21 hours in order to determine the nature and time course of phagocytosis of these organisms. Aliquotes of the interacting cells were taken at various time intervals for electron microscopic examination. Some specimens had their zona pellucidae enzymatically removed prior to incubation with yeast, and these specimens showed the most extensive interaction and phagocytosis of Candida. The zona pullucida appears to be an effective barrier to yeast, at least over the time span studied. The observations are consistent with the hypothesis of an initial attachment of yeast via a surface component to oocyte microvilli followed by phagocytic uptake into an endosome. There is no compelling evidence of lysosomal degradation of the yeast over the time course of this study; however, the oocytes appear to undergo some degenerative changes at long incubation times.

    Title Unexpected Sequence Diversity in the Amino-terminal Ends of the Coat Proteins of Strains of Sugarcane Mosaic Virus.
    Date March 1991
    Journal The Journal of General Virology
    Excerpt

    The sequence of the 3'-terminal 1343 nucleotides of the SC strain of the sugarcane mosaic virus (SCMV-SC) genome was compared with the 1376 nucleotides at the 3' terminus of maize dwarf mosaic virus B (MDMV-B). The SCMV-SC sequence includes an open reading frame which codes for the viral coat protein of 313 amino acids (nucleotides 157 to 1116), followed by a 3' non-coding region of 235 nucleotides and a poly(A) tail. The MDMV-B sequence codes for the capsid protein (nucleotides 157 to 1139) of 328 amino acids and has a 3' non-coding region of 236 nucleotides. The coat protein of SCMV-SC has 92% identity with that of MDMV-B except for the region between amino acid residues 27 and 70 of SCMV-SC. This region of SCMV-SC is smaller (44 residues) than the equivalent region in MDMV-B (59 residues) and has only 22% identity with the MDMV-B sequence. Possible mechanisms for the generation of this sequence diversity are discussed. Despite this diversity, the sequence identities of both the major part of the coat proteins and the 3' non-coding regions confirm the proposal, based on previously described serological data, that SCMV-SC and MDMV-B are strains of SCMV.

    Title Translation of the Humeral Head on the Glenoid with Passive Glenohumeral Motion.
    Date December 1990
    Journal The Journal of Bone and Joint Surgery. American Volume
    Excerpt

    We have demonstrated that certain passive motions of the glenohumeral joint are reproducibly accompanied by translation of the head of the humerus on the glenoid. We investigated the relationship of these translations to the position of the glenohumeral joint and to applied torques and forces in seven isolated glenohumeral joints from fresh cadavera, using a six-degrees-of-freedom position sensor and a six-axis force and torque transducer. Reproducible and significant translation occurred in an anterior direction with glenohumeral flexion and in a posterior direction with extension. We also observed translation with cross-body movement. The translation occurring with flexion was obligate in that it could not be prevented by the application of an oppositely directed force of thirty to forty newtons. Operative tightening of the posterior portion of the capsule increased the anterior translation on flexion and cross-body movement and caused it to occur earlier in the arc of motion compared with the intact glenohumeral joint. Operative tightening of the posterior part of the capsule also resulted in significant superior translation with flexion of the glenohumeral joint.

    Title Lysobactin, a Novel Antibacterial Agent Produced by Lysobacter Sp. Ii. Biological Properties.
    Date February 1989
    Journal The Journal of Antibiotics
    Excerpt

    Lysobactin, an antibiotic isolated from a strain of Lysobacter, is 2 to 4-fold more active than vancomycin against aerobic and anaerobic Gram-positive bacteria. Included in the spectrum of lysobactin are Staphylococci, Streptococci, corynebacteria, clostridia and various other Gram-positive anaerobic bacteria. The activity of lysobactin against aerobic and anaerobic Gram-negative bacteria is poor. When given parenterally the compound was efficacious in systemic staphylococcal and streptococcal infections in mice. Similarly, when applied topically lysobactin was also curative in a staphylococcal wound infection in mice. Some studies on the mode of action of lysobactin are presented.

    Title In Vivo Depression of Reserve Albumin Binding Capacity by Cadmium: a Preliminary Evaluation.
    Date April 1988
    Journal Life Sciences
    Excerpt

    The effect of cadmium upon the depression of reserve albumin binding capacity (%RABC) was investigated in male, New Zealand white rabbits at daily dosages of 0.65 mg and 0.90 mg Cd/kg body weight. Correlations of % RABC to the duration of exposure were strongest at the higher dosage. After 30-35 days exposure, the decline in % RABC was partially reversed. Levels of total protein in urine increased sharply within a few days after the % RABC had been reduced by cadmium to their lowest values.

    Title Anatomy of the Abductor Muscles of the Hip As Studied by Computed Tomography.
    Date November 1987
    Journal The Journal of Bone and Joint Surgery. American Volume
    Excerpt

    Computed tomography provides a non-invasive method for studying anatomy in live subjects. The abductor muscles of the hip were studied by using computed tomography to describe their position, size, and orientation. The outlines of the muscles were clearly identifiable; patterns that are associated with trauma, arthritis, and so on, differed from normal. The patterns in eighteen normal hips in twelve adults were mapped in detail. The cross-sectional areas of the abductor muscles were measured and vectors representing the total pull of the abductor muscle in the frontal and sagittal planes were constructed for each hip. The variations in individual and composite muscular anatomy were recorded. The inclination of the axis of the abductor muscle ranged from 17 to 26 degrees (standard deviation, 2.9 degrees) in the frontal plane and from -2 to 14 degrees (standard deviation, 4.2 degrees) in the sagittal plane.

    Title In Vivo Evaluation of Tigemonam, a Novel Oral Monobactam.
    Date May 1987
    Journal Antimicrobial Agents and Chemotherapy
    Excerpt

    Tigemonam, a new monobactam with excellent activity against gram-negative bacteria, was evaluated for in vivo efficacy and absorption after oral administration to laboratory animals. Tigemonam is absorbed when administered orally to mice and dogs. In a variety of gram-negative systemic infections in mice, orally administered tigemonam was efficacious in all infections studied. Comparison drugs such as amoxicillin, cephalexin, and cefaclor were less efficacious, especially in infections caused by beta-lactamase-producing organisms. In localized infections, tigemonam also demonstrated excellent in vivo activity. In acute pyelonephritis in mice caused by Escherichia coli or Proteus sp., tigemonam was very effective. In a rat lung model with Klebsiella pneumoniae, tigemonam was active with a median effective dose of 46 mg/kg compared with 160 mg/kg for cefaclor and over 200 mg/kg for amoxicillin. Tigemonam was well absorbed in laboratory animals and with its excellent gram-negative spectrum of activity should prove of value in oral antibiotic therapy in humans.

    Title Hyperbaric Hyperoxia Reversibly Inhibits Erythrocyte Phospholipid Fatty Acid Turnover.
    Date May 1987
    Journal Journal of Applied Physiology (bethesda, Md. : 1985)
    Excerpt

    The present study is one component of a comprehensive investigation of oxygen tolerance of tissues and organs in normal human subjects. The focus of this study was the acylation of membrane phospholipid in situ by erythrocytes. Activation of exogenous [9,10-3H]oleic acid to acyl thioester and transesterification of the acyl thioester into phospholipid by intact human erythrocytes incubated in vitro decreased 30% after exposure of 10 human subjects to hyperbaric hyperoxia (100% O2, 3 ATA, 3.5 h). Partial recovery of activity could be detected when additional cells were obtained from these subjects and assayed in vitro 24 h after cessation of exposure. No significant change in membrane phospholipid fatty acid composition was detected under these conditions. The reduced glutathione content of intact erythrocytes increased by 15% after hyperbaric hyperoxia and remained elevated 24 h after exposure. In isolated membranes prepared from the same cells activation of [9,10-3H]oleic acid to acyl thioester and its transesterification into phospholipid did not change after hyperoxia. Since the ability of intact cells to replace oxidized fatty acids in membrane phospholipids via deacylation and reacylation in situ may be necessary for the maintenance of membrane integrity during exposure to oxidative stress, the decrease in [9,10-3H]oleic acid incorporation by human erythrocytes detected in vitro after hyperbaric hyperoxia in vivo may reflect an early event in the pathogenesis of oxygen-induced cellular injury and may be a useful index for assessment of the tolerance of tissues to hyperoxia.

    Title Prosthetic Replacement for Chronic Unreduced Dislocations of the Shoulder.
    Date April 1987
    Journal Clinical Orthopaedics and Related Research
    Excerpt

    Seven patients with chronic dislocations of the shoulder were treated by humeral head or total shoulder replacement. All patients had significant humeral head damage. Three dislocations were posterior and four were anterior. All had been unreduced for at least two months. A Neer prosthesis was used in each patient and the version of the humeral component was altered by 30 degrees-50 degrees away from the direction of the dislocation. Only a sling and swathe was used postoperatively, and the patient was allowed early motion in a limited-goals physical therapy program. There were no redislocations and all patients were improved over their preoperative status. Five patients achieved a good result and two had a fair result based on a 100-unit rating system. One transient axillary nerve palsy occurred, but there were no other complications. Prosthetic replacement for chronic unreduced shoulder dislocations is a reliable procedure when severe humeral head damage exists.

    Title Evaluation of Aztreonam, Cefoperazone, Latamoxef and Ceftazidime in the Hamster Colitis Model.
    Date March 1987
    Journal The Journal of Antimicrobial Chemotherapy
    Excerpt

    Aztreonam, ceftazidime, cefoperazone and latamoxef (moxalactam) were evaluated in a hamster model for antibiotic-associated colitis. Aztreonam, a novel monocyclic beta-lactam antibiotic specifically directed against aerobic Gram-negative bacteria with limited activity against Gram-positive and anaerobic bacteria did not cause haemorrhagic caecitis and death in hamsters when administered intraperitioneally or orally. Quantitative caecal cultures showed no changes in the anaerobic caecal microflora of hamsters treated intraperitoneally with aztreonam and only a temporary decrease in anaerobic Gram-negative bacilli in hamsters treated orally. Clostridium difficile and its cytotoxin were not present in these animals. Parenteral administration of ceftazidime also did not affect the anaerobic caecal microflora or cause caecitis. However, when given orally, ceftazidime suppressed the anaerobic caecal microflora and a lethal C. difficile-induced caecitis developed. Latamoxef or cefoperazone given parenterally resulted in caecitis and death in five days with marked changes in the anaerobic caecal microflora and C. difficile present in the caecal contents of these animals. The lethal haemorrhagic caecitis observed in this study was indistinguishable from that seen in the clindamycin-induced colitis model in the hamster. The possible correlation of these findings to gastrointestinal disturbances as a complication of antibiotic therapy in humans is discussed.

    Title Characterization of the Atp-promoted Aspect of Na+-ca2+ Exchange Present in Squid Retinal Nerve Axolemma.
    Date October 1986
    Journal Biochimica Et Biophysica Acta
    Excerpt

    Using an in vitro system which consists of an axolemma-rich vesicle fraction prepared from squid retinal nerve fibers, an Na+-Ca2+ exchange process has been characterized and appears identical with that reported in squid giant axon. This exchange is absolutely dependent on the establishment of an Na+ gradient, shows monovalent and divalent cation specificity and is highly sensitive to monensin, A23187 and valinomycin but not to ouabain, digitoxigenin, vanadate, pentylenetetrazole, tetrodotoxin or tetraethylammonium. Furthermore, it was found that the exchange process is enhanced by the addition of ATP. This ATP-promoted aspects of Na+-Ca2+ exchange shares many similar characteristics with Na+-Ca2+ ATP hydrolysis and may indicate a common mechanism for both activities via a protein phosphorylation-dephosphorylation event.

    Title Effect of Hyperbaric Oxygen Exposure on Oxygen Tension Within the Medullary Canal in the Rabbit Tibial Osteomyelitis Model.
    Date September 1986
    Journal Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society
    Excerpt

    The effect on intramedullary oxygen tension of 100% oxygen exposure at 1, 2, 2.4, and 3 atm pressure was studied in 12 New Zealand white rabbits with chronic right tibial osteomyelitis. The model, modified from that described by others, incorporates a multipuncture silastic closure plug placed transcortically in the proximal tibial metaphysis through which platinum needle, polarographic electrode oxygen tension determinations can be made without repeat surgical exposure. In 40% of the control, left, noninfected tibial metaphyses the baseline oxygen tension with the animals breathing room air at sea level was suboptimal for leukocyte bacterial killing. This oxygen tension was depressed further in the infected right tibia. Medullary canal oxygen tension increased in response to hyperbaric oxygen exposure in both the infected and noninfected tibiae. Whereas the amount of the oxygen tension increase varied with the presence of infection and depth of dive, neither the time for oxygen tension to plateau nor the time required for return to baseline tension after completion of hyperbaric oxygen exposure varied with the presence of infection or depth of dive. After completion of hyperbaric oxygen exposure, the oxygen tension within the medullary canal returned to baseline within 15 min.

    Title Improved Determination of Cadmium in Blood and Plasma by Flameless Atomic Absorption Spectroscopy.
    Date June 1986
    Journal Bulletin of Environmental Contamination and Toxicology
    Title Auditory and Vestibular Function in Hyperbaric Oxygen.
    Date September 1985
    Journal Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-head and Neck Surgery
    Excerpt

    The therapeutic value of high partial pressures of oxygen is limited by the toxicity of oxygen. Pulmonary damage, visual impairment, and convulsions are known hazards during hyperoxic exposure, but dose-effect relationships have not been quantified for specific organs or functions. As part of an integrated study of organ oxygen tolerance in man (Predictive Study V of the Institute for Environmental Medicine), auditory and vestibular function was evaluated in man before, during, and after exposure to 100% oxygen at 3 atmospheres absolute pressure for 2 to 3.5 hours. No alterations in hearing or equilibrium were detected, suggesting that ototoxicity is not a factor that would limit exposure under these conditions.

    Title Regulation of Discoidin I Gene Expression in Dictyostelium Discoideum by Cell-cell Contact and Camp.
    Date July 1985
    Journal Journal of Cellular Biochemistry
    Excerpt

    We have previously presented evidence that cell-cell contact is the normal developmental signal to deactivate discoidin I gene expression in D discoideum [Berger EA, Clark JM: Proc Natl Acad Sci USA 80:4983, 1983]. Here we provide genetic evidence to support this hypothesis by examining gene expression in a cohesion-defective mutant, strain EB-21, which enters the developmental program but is blocked at the loose mound stage. When this strain was developed in suspension, the cells remained almost entirely as single amoebae, unlike the wild type, which formed large multicellular aggregates. In both strains, discoidin I mRNA levels were low in vegetative cells but rose sharply during the first few hours of development. However, the peak level reached at 8 hr in EB-21 exceeded that observed in wild type, and while the level declined markedly over the next few hours in wild type, it remained highly elevated in the mutant. Thus, there was a correlation between the inability of EB-21 to form normal cell-cell contacts and its deficiency in inactivating discoidin I gene expression. Previous studies from several laboratories, including this one, have demonstrated that exogenously added cAMP can block or reverse the changes in gene expression normally seen upon cell disaggregation. This has led us to propose that cAMP serves as a second messenger regulating the expression of contact-regulated genes. Here we provide additional support for this hypothesis. Intracellular cAMP levels rapidly dropped several-fold when wild type tight cell aggregates were disaggregated and remained low as the cells were cultured in the disaggregated state. Furthermore, overexpression of discoidin I mRNA late in development in EB-21 was corrected by addition of high concentrations of cAMP. These results are consistent with a second messenger function for cAMP in the contact-mediated regulatory response, and they indicate that the cAMP response machinery for discoidin I gene expression is capable of functioning in the cohesion-defective EB-21 strain.

    Title Human Respiration at Rest in Rapid Compression and at High Pressures and Gas Densities.
    Date April 1983
    Journal Journal of Applied Physiology: Respiratory, Environmental and Exercise Physiology
    Excerpt

    Ventilation (V), end-tidal PCO2 (PACO2), and CO2 elimination rate were measured in men at rest breathing CO2-free gas over the pressure range 1-50 ATA and the gas density range 0.4-25 g/l, during slow and rapid compressions, at stable elevated ambient pressures and during slow decompressions in several phases of Predictive Studies III-1971 and Predictive Studies IV-1975. Inspired O2 was at or near natural O2 levels during compressions and at stable high pressures; it was 0.5 ATA during decompressions. Rapid compressions to high pressures did not impair respiratory homeostasis. Progressive increase in pulmonary gas flow resistance due to elevation of ambient pressure and inspired gas density to the He-O2 equivalent of 5,000 feet of seawater was not observed to progressively decrease resting V, or to progressively increase resting PACO2. Rather, a complex pattern of change in PACO2 was seen. As both ambient pressure and pulmonary gas flow resistance were progressively raised, PACO2 at first increased, went through a maximum, and then declined towards values near the 1 ATA level. It is suggested that this pattern of PACO2 change results from interaction on ventilation of 1) increase in pulmonary resistance due to elevation of gas density with 2) increase in respiratory drive postulated as due to generalized CNS excitation associated with exposure to high hydrostatic pressure. There may be a similar interaction between increased gas flow resistance and increase in respiratory drive related to nitrogen partial pressure and the narcosis resulting therefrom.

    Title Successful Therapy of Cerebral Air Embolism with Hyperbaric Oxygen at 2.8 Ata.
    Date August 1982
    Journal Undersea Biomedical Research
    Excerpt

    A 60-year-old male patient suddenly developed blindness, agitation, and disorientation 36 h after coronary bypass surgery. Onset of symptoms followed efforts to clear an air-filled radial artery cannula. Seven hours after onset of symptoms, initial compression to 2.8 ATA (60 fsw), 100% oxygen (U.S. Navy Table 6), steroids, intravenous fluids, and antiplatelet drugs were used for therapy. The patient's agitation and disorientation dictated that we avoid initial compression to 6 ATA (165 fsw), contrary to conventional practice in therapy of air embolism, and instead immediately give oxygen at 2.8 ATA. After a second treatment with USN Table 6, given 6 h after the first, the patient's vision and mental state returned to normal. He subsequently had an uneventful recovery from surgery and cerebral air embolism.

    Title Characterization of Polysaccharide Accumulation in a Cell Division Defective Mutant of Escherichia Coli 15t-.
    Date March 1982
    Journal Journal of General Microbiology
    Excerpt

    Escherichia coli 15T-R1, a temperature-dependent cell division mutant, grows into filaments of various lengths (200 to 500 microgram) at 24 degrees C, but divides essentially normally at 37 degrees C. When grown to late-exponential phase at the restrictive temperature, the elongated cells showed discrete areas of increased density at polar regions and other sites in the cytoplasm, when viewed by phase contrast microscopy. Electron microscopy of preparations specifically stained for polysaccharide revealed clusters of granules with a similar distribution pattern to that of the dense areas seen by phase contrast microscopy. The granules were susceptible to alpha-amylase digestion, and chemical analysis of the extracted and purified polysaccharide showed that it consisted of polyglucose, including glycogen. At 24 degrees C the R1 cells contained about twice as much polyglucose and four times as much glucogen as at 37 degrees C.

    Title Systemic Gas Embolus: a Discussion of Its Pathogenesis in the Neonate, with a Review of the Literature.
    Date October 1977
    Journal American Journal of Diseases of Children (1960)
    Excerpt

    We report, a term newborn infant with congenital vocal cord paralysis and congenital viral myocarditis. In her five days of life she developed a pneumomediastinum, pneumopericardium, subcutaneous emphysema, and terminally a pneumothorax and systemic air embolus. This unusual case is used to develop a concept of the pathogenesis of extraventilatory air, and is also represented in diagrammatic form.

    Title Umbilical Artery Catheterization by a Cutdown Procedure.
    Date July 1977
    Journal Pediatrics
    Excerpt

    In severely ill newborns conventional methods of umbilical artery catheterization sometimes fail to achieve a functioning intravascular line. In 18 of 19 such newborns requiring umbilical artery catheters for optimal management, successful catheterization was attained using a cutdown procedure on the umbilical arteries. Vascular perforation within the anulus umbilicalis, tunica intima invagination ahead of an advancing catheter, and subintimal cannulation were defined as the causes of initial catheterization failure in all 19 newborns.

    Title Basophil Hypersensitivity Response in Rabbits.
    Date March 1977
    Journal Infection and Immunity
    Excerpt

    A cutaneous basophil hypersensitivity response has been observed in rabbits immunized with bovine serum albumin and challenged intradermally with this antigen 7 days later. The cellular response appears to be similar to cutaneous basophil hypersensitivity reported in guinea pigs and humans. A basophil response was also observed in rabbits immunized with Staphylococcus aureus and challenged with viable staphylococcal cells 7 days later. A method of observing basophil infiltration in rabbits by means of connective tissue spreads obtained from the subcutaneous connective tissue is described. The rabbit should serve as an excellent model for the study of basophil responses as these animals have a significant basophil component with few if any tissue mast cells which may be confused both morphologically and functionally with the basophil.

    Title Resuscitation Equipment Board for Nurseries and Delivery Rooms.
    Date January 1977
    Journal Jama : the Journal of the American Medical Association
    Excerpt

    A resuscitation equipment board for mounting in delivery rooms and nurseries facilitates orderly and effective resuscitation of asphyxiated neonates.

    Title Pulmonary Oxygen Toxicity: a Review.
    Date July 1972
    Journal Pharmacological Reviews
    Title Sequence Studies of Satellite Tobacco Necrosis Virus Rna. Isolation and Characterization of a 5'-terminal Trinucleotide.
    Date January 1972
    Journal Journal of Molecular Biology
    Title The Measurement of Intracranial Echo Pulsations.
    Date December 1971
    Journal Medical & Biological Engineering
    Title Ultrasonic Studies of Brain Movements.
    Date October 1971
    Journal Neurology
    Title Ultrasonic Echo Pulsations in Range. A Study of Rise Times and Delay Times.
    Date July 1971
    Journal Acta Neurochirurgica
    Title Rate of Development of Pulmonary O2 Toxicity in Man During O2 Breathing at 2.0 Ata.
    Date June 1971
    Journal Journal of Applied Physiology
    Title Alveolar-arterial O2 Differences in Man at 0.2, 1.0, 2.0, and 3.5 Ata Inspired Po2.
    Date June 1971
    Journal Journal of Applied Physiology
    Title The Deformation of the Ultrasonic Field in Passage Across the Living and Cadaver Head.
    Date May 1971
    Journal Medical & Biological Engineering
    Title Pulsatile Echo-encephalography.
    Date January 1971
    Journal Acta Neurologica Scandinavica. Supplementum
    Title Experimental Observations on the Origin of the M-echo.
    Date April 1970
    Journal Medical & Biological Engineering
    Title Inferential Observations on the Origin of the M-echo.
    Date April 1970
    Journal Medical & Biological Engineering
    Title Interpreter Error in Echoencephalography.
    Date August 1969
    Journal Neurology
    Title A Calibrating Device for Variations in Range of Ultrasonic Echoes.
    Date July 1969
    Journal Medical & Biological Engineering
    Title Transient Unilateral Loss of Vision Associated with Oxygen at High Pressure.
    Date May 1969
    Journal Archives of Ophthalmology
    Title Effect of the Skull in Degrading the Display of Echoencephalographic B and C Scans.
    Date January 1969
    Journal The Journal of the Acoustical Society of America
    Title Action of Spleen Phosphodiesterase Uponsoluble Ribonucleic Acid.
    Date August 1968
    Journal Archives of Biochemistry and Biophysics
    Title Effect of Oxygen at 2 Atmospheres on the Pulmonary Mechanics of Normal Man.
    Date May 1968
    Journal Journal of Applied Physiology
    Title Alterations in the Pulmonary Capillary Bed During Early O2 Toxicity in Man.
    Date May 1968
    Journal Journal of Applied Physiology
    Title The Satellite Tobacco Necrosis Virus in Studies of Genetic Coding.
    Date April 1968
    Journal Cold Spring Harbor Symposia on Quantitative Biology
    Title The in Vitro Translation of a Monocistronic Message.
    Date July 1966
    Journal Proceedings of the National Academy of Sciences of the United States of America
    Title Inhibitors of the Transfer of Amino Acids from Aminoacyl Soluble Ribonucleic Acid to Proteins.
    Date February 1966
    Journal The Journal of Biological Chemistry
    Title Mammal-like Dentition in a Mesozoic Crocodylian.
    Date
    Journal Science (new York, N.y.)
    Excerpt

    Crocodylian teeth are generally conical with little differentiation in shape along the tooth row. The mandible is incapable of any fore-aft movement, and feeding typically involves little or no intraoral processing. Complex, multi-cusped, mammal-like teeth differentiated along the tooth row have been found in a Cretaceous crocodylian from Malawi. The morphology of the teeth and mandible indicates that food items were processed by back-to-front (proal) movement of the mandible, unlike living crocodylians but as in some mammals and Sphenodon (the tuatara).

    Title Simultaneous Light Scattering and Intrinsic Fluorescence Measurement for the Classification of Airborne Particles.
    Date
    Journal Applied Optics
    Excerpt

    We describe a prototype laboratory light-scattering instrument that integrates two approaches to airborne particle characterization: spatial light-scattering analysis and intrinsic fluorescence measurement, with the aim of providing an effective means of classifying biological particles within an ambient aerosol. The system uses a single continuous-wave 266-nm ultraviolet laser to generate both the spatial elastic scatter data (from which an assessment of particle size and shape is made) and the particle intrinsic fluorescence data from particles in the approximate size range of 1-10-mum diameter carried in a sample airflow through the laser beam. Preliminary results suggest that this multiparameter measurement approach can provide an effective means of classifying different particle types and can reduce occurrences of false-positive detection of biological aerosols.

    Title Measurement of Weight in Clinical Trials: is One Day Enough?
    Date
    Journal Journal of Obesity (online)
    Excerpt

    Background. Weight is typically measured on a single day in research studies. This practice assumes negligible day-to-day weight variability, although little evidence exists to support this assumption. We compared the precision of measuring weight on one versus two days among control participants in the Weight Loss Maintenance trial. Methods. Trained staff measured weight on two separate days at baseline, 12 months, and 30 months (2004-2007). We calculated the standard deviation (SD) of mean weight change from baseline to the 12- and 30-month visits using (a) the first and (b) both daily weights from each visit and conducted a variance components analysis (2009). Results. Of the 316 participants with follow-up measurements, mean (SD) age was 55.8 (8.5) years, BMI was 30.8 (4.5) kg/m(2), 64% were women, 36% were black, and 50% were obese. At 12 months, the SD of mean weight change was 5.1 versus 5.0 kg using one versus two days of weight measurements (P = .76), while at 30 months the corresponding SDs were 6.3 and 6.3 kg (P = .98). We observed similar findings within subgroups of BMI, sex, and race. Day-to-day variability within individuals accounted for <1% of variability in weight. Conclusions. Measurement of weight on two separate days has no advantage over measurement on a single day in studies with well-standardized weight measurement protocols.

    Title Risk of Complications After Bariatric Surgery Among Individuals with and Without Type 2 Diabetes Mellitus.
    Date
    Journal Surgery for Obesity and Related Diseases : Official Journal of the American Society for Bariatric Surgery
    Excerpt

    BACKGROUND: Type 2 diabetes mellitus is highly prevalent in obese individuals. Bariatric surgery, promoted for reducing the medical problems of morbid obesity, has been increasingly recognized for its particular efficacy in treating diabetes. However, before bariatric surgery can be recommended for the treatment of diabetes, its safety in the diabetic population must be known. We assessed the odds of complications after bariatric surgery in patients with and without diabetes. METHODS: This was a retrospective cohort study. Using an administrative database from 7 Blue Cross/Blue Shield plans, we identified 22,288 subjects who had undergone bariatric surgery from 2002 to 2008. From this cohort, we selected 6754 pairs of surgical patients (1 with and 1 without diabetes) matched by age, gender, health plan, and year of surgery. With conditional logistic regression analysis, we determined the relative odds of postoperative complications for ≤12 months after surgery in the 2 groups. RESULTS: The mean age of the surgical patients was 46 years, and 79% were women. Postoperative complications were rare and comparable in those with and without diabetes. The most common complications were nausea, vomiting, and abdominal pain (8.8%), the need for a gastric revision procedure (5.0%), and upper endoscopy (2.3%). Select cardiac, infectious, and renal complications occurred more frequently in the diabetic group. The incidence of cardiac complications was greater in the 2-3-month and 4-6-month postoperative periods (odds ratio [OR] 1.7, P < .001), the incidence of infectious complications was greater in the 0-1-month (OR 1.3, P < .02) and 4-6-month (OR 1.8, P < .001) periods, and the incidence of renal complications was greater in the 2-3-month postoperative period (OR 4.6, P = .01). CONCLUSIONS: Our findings support the safety of bariatric surgery in obese individuals with diabetes, although management strategies to avert postoperative cardiac, infectious, and renal complications in this population might be warranted.

    Similar doctors nearby

    Dr. Nelson Isada

    Internal Medicine
    34 years experience
    Anchorage, AK

    Dr. Peter Hulman

    Internal Medicine
    29 years experience
    Anchorage, AK

    Dr. Catherine Kilby

    Internal Medicine
    19 years experience
    Anchorage, AK

    Dr. Keith Brownsberger

    Internal Medicine
    Anchorage, AK

    Dr. Mary Demers

    Internal Medicine
    27 years experience
    Anchorage, AK

    Dr. Julie McCormick

    Internal Medicine
    16 years experience
    Anchorage, AK
    Search All Similar Doctors