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Credentials

Education ?

Medical School Score Rankings
The University of Texas at Houston (1984)
  •  
Top 50%

Affiliations ?

Dr. Morgan is affiliated with 5 hospitals.

Hospital Affiliations

  • Pine Creek Medical Center
    9032 Harry Hines Blvd, Dallas, TX 75235
  • Pine Creek Hospital
  • St Paul Medical Center
  • Medical City Hospital
  • Valley View Surgical Center
  • Publications & Research

    Dr. Morgan has contributed to 239 publications.
    Title Prognostic Implications and Molecular Associations of Nadh Dehydrogenase Subunit 4 (nd4) Mutations in Acute Myeloid Leukemia.
    Date March 2012
    Journal Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.k
    Excerpt

    To study the prevalence and prognostic importance of mutations in NADH dehydrogenase subunit 4 (ND4), a mitochondrial encoded transmembrane component of the electron transport chain respiratory Complex I, 452 AML patients were examined for ND4 mutations by direct sequencing. The prognostic impact of ND4 mutations was evaluated in the context of other clinical prognostic markers and genetic risk factors. In all, 29 of 452 patients (6.4%) had either somatic (n=12) or germline (n=17) ND4 mutations predicted to affect translation. Somatic mutations were more likely to be heteroplasmic (P<0.001), to occur in predicted transmembrane domains (P<0.001) and were predicted to have damaging effects upon translation (P<0.001). Patients with somatically acquired ND4 mutations had significantly longer relapse-free survival (P=0.017) and overall survival (OS) (P=0.021) than ND4(wildtype) patients. Multivariate analysis also demonstrated a tendency for increased survival in patients with somatic ND4 mutations (RFS: hazard ratio (HR) 0.25, confidence interval (CI) 0.06-1.01, P=0.052; OS: HR 0.29, CI 0.74-1.20, P=0.089). Somatic ND4(mutated) patients had a higher prevalence of concomitant DNMT3A mutations (P=0.023) and a higher percentage of the NPM1/FLT3-ITD low-risk genotype (P=0.021). Germline affected cases showed higher BAALC (P=0.036) and MLL5 (P=0.051) expression levels. Further studies are warranted to validate the favorable prognostic influence of acquired ND4 mutations in AML.

    Title Re: No Good Options. J. A. Smith, Jr. J Urol 2011; 185: 8-9.
    Date August 2011
    Journal The Journal of Urology
    Title Looking Beyond Recurrence: Comorbidities in Cancer Survivors.
    Date May 2011
    Journal Clinical Journal of Oncology Nursing
    Excerpt

    Cancer recurrence is a very real concern for cancer survivors. Surveillance for recurrence and vigilance for development of new cancers are top priorities during follow-up visits after active treatment ends. However, the cancer survivor also is at risk for the development of comorbid conditions. These conditions, including obesity, diabetes, dyslipidemia, menopause, decreased bone mass, hypertension, and hypothyroidism, are discussed with their relevance for general health and their relationships to disease-specific cancers. All of these conditions should be routinely addressed as part of the patient's survivorship care when appropriate. The oncology nurse is in a prime position to educate survivors about the risks for these conditions, both through evidence-based practice guidelines specific to each condition and also through the use of a treatment summary and care plan. This article discusses these selected comorbidities and offers strategies for nurses to address them with survivors during follow-up visits. Clinical practice guidelines for comorbidities are included, along with oncology implications and relevance for survivors. Recommendations for modifiable risk factors and healthy living also are included, along with Web sites for survivorship care plans.

    Title A 1.5 Hour Procedure for Identification of Enterococcus Species Directly from Blood Cultures.
    Date April 2011
    Journal Journal of Visualized Experiments : Jove
    Excerpt

    Enterococci are a common cause of bacteremia with E. faecalis being the predominant species followed by E. faecium. Because resistance to ampicillin and vancomycin in E. faecalis is still uncommon compared to resistance in E. faecium, the development of rapid tests allowing differentiation between enterococcal species is important for appropriate therapy and resistance surveillance. The E. faecalis OE PNA FISH assay (AdvanDx, Woburn, MA) uses species-specific peptide nucleic acid (PNA) probes in a fluorescence in situ hybridization format and offers a time to results of 1.5 hours and the potential of providing important information for species-specific treatment. Multicenter studies were performed to assess the performance of the 1.5 hour E. faecalis/OE PNA FISH procedure compared to the original 2.5 hour assay procedure and to standard bacteriology methods for the identification of enterococci directly from a positive blood culture bottle.

    Title Allergic Respiratory Disease As a Potential Co-morbidity for Hypertension.
    Date January 2011
    Journal Cardiology Journal
    Excerpt

    This article examines the relationships between allergic rhinitis and hypertension, chronic sinusitis and hypertension, and asthma and hypertension. Previous studies have demonstrated that men reporting seasonal or chronic rhinitis had on average a 3.5 mm Hg higher systolic blood pressure than those without allergic rhinitis. Proposed mechanisms to the relationship between allergic rhinitis and sinusitis with hypertension may lie in the pathway of obstructive sleep apnea via neurohumoral responses to hypoxemia. Asthmatics were 1.4 times more likely to have heart disease, and 1.3 times more likely to have high blood pressure, than non-asthmatics. The commonality of immunological dysfunction and inflammation between diseases of allergy and those mediated by hypertension and other vascular disorders may explain the correlations observed. Interestingly, obese individuals have higher levels of circulating IL-6, leptin and TNF-alpha skewing the immune system toward the allergen-reactive type 2 helper T-cell. This would mean that obese individuals were predisposed to diseases of chronic inflammation. The implications of allergic rhinitis, chronic sinusitis, and asthma deserve closer attention, especially into the possibility of co-morbidity for hypertension. Although associations between allergic diseases and hypertension have been reported, more studies need to be performed to elucidate the mechanisms behind such associations.

    Title Obstetrician-gynaecologist Knowledge of and Access to Information About the Risks of Medication Use During Pregnancy.
    Date January 2011
    Journal The Journal of Maternal-fetal & Neonatal Medicine : the Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians
    Excerpt

    To assess opinions, knowledge, and informational resources of obstetrician-gynaecologists regarding the safety of medication use during pregnancy.

    Title Prospective Comparison of the Perceived Preoperative Computed Tomographic, Endosonographic and Histopathological Stage of Oesophageal Cancer Related to Body Mass Indices.
    Date November 2010
    Journal European Radiology
    Excerpt

    Pre-morbid weight loss and low body mass index (BMI) have been reported to be associated with decreased odds of misclassification of the defined stage of oesophageal cancer by endoluminal ultrasound (EUS). The aim of this study was to assess the strengths of agreement between the perceived preoperative radiological T and N stage compared with the final histopathological stage related to four categories of BMI (low <20, normal 20-24.9, high 25-30, and obese >30 kg/m(2)). One hundred sixty-six patients with oesophageal carcinoma were studied. Strength of agreement between the CT and EUS stages and histopathological stage was determined by the weighted kappa statistic (Kw). Kw for EUS T stage related to increasing BMI category was 0.840 (P = 0.0001) to 0.620 (P = 0.001), compared with 0.415 (P = 0.018) to 0.260 (P = 0.011) for CT. Kw for EUS N stage related to increasing BMI category was 0.438 (P = 0.067) to 0.513 (P = 0.010), compared with 0.143 (P = 0.584) to 0.582 (P = 0.030) for CT. EUS was good at predicting tumour infiltration irrespective of BMI when compared with CT, while CT N staging accuracy improved with higher BMIs. Multidisciplinary teams should be aware of these limitations when planning treatment strategies.

    Title Management of Prescription and Nonprescription Drug Use During Pregnancy.
    Date November 2010
    Journal The Journal of Maternal-fetal & Neonatal Medicine : the Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians
    Excerpt

    To assess screening and treatment patterns of obstetrician-gynecologists regarding medication use during pregnancy.

    Title Obstetrician-gynecologists' Approach to Well-woman Care.
    Date September 2010
    Journal Obstetrics and Gynecology
    Excerpt

    To estimate obstetrician-gynecologists' attitudes and management practices regarding well-woman care.

    Title Screening of Herbal Extracts Against Multi-drug Resistant Acinetobacter Baumannii.
    Date September 2010
    Journal Phytotherapy Research : Ptr
    Excerpt

    Antibiotic resistance is increasing resulting in a decreasing number of fully active antimicrobial agents available to treat infections with multi-drug resistant (MDR) bacteria. Herbal medicines may offer alternative treatment options. A direct inoculation method simulating the standard disc diffusion assay was developed to determine in vitro antimicrobial activity of sixty herbal extracts against MDR-Acinetobacter baumannii (A. baumannii). Eighteen herbal extracts inhibited MDR-A. baumannii on agar plates, although the magnitude and quality of bacterial inhibition differed considerably among the antibacterial herbal extracts. Next, minimal inhibitory concentration (MIC) of these antibacterial herbal extracts was calculated using a broth microdilution assay. For most herbal extracts, the larger the zone of inhibition on agar plates, the lower the MIC. In general, hetero-resistance on agar plates correlated with higher MIC. The skip well phenomenon was seen with two herbal extracts. In conclusion, 30% of the screened herbal extracts demonstrated in vitro antibacterial activity against MDR-A. baumannii using similar rigorous testing methods as those commonly employed for assessing antimicrobial activity of synthetic antibacterial agents. Characterization of a specific compound conferring this antibacterial activity of the herbal extracts may help to identify novel antimicrobial agents active against highly resistant bacteria.

    Title Recent Advances in Combined Modality Therapy.
    Date September 2010
    Journal The Oncologist
    Excerpt

    Combined modality therapy emerged from preclinical data showing that carefully chosen drugs could enhance the sensitivity of tumor cells to radiation while having nonoverlapping toxicities. Recent advances in molecular biology involving the identification of cellular receptors, enzymes, and pathways involved in tumor growth and immortality have resulted in the development of biologically targeted drugs. This review highlights the recent clinical data in support of newer generation cytotoxic chemotherapies and systemic targeted agents in combination with radiation therapy.

    Title Carboplatin Plus Weekly Docetaxel As Salvage Chemotherapy in Docetaxel-resistant and Castration-resistant Prostate Cancer.
    Date August 2010
    Journal World Journal of Urology
    Excerpt

    There is no proven, effective, standard second-line chemotherapy for castration- and docetaxel-resistant prostate cancer (DRPC). Recent data suggest that carboplatin may be effective in combination with docetaxel in this setting; however, the optimal docetaxel/carboplatin-based regimen is still unclear.

    Title A Tagging-via-substrate Approach to Detect the Farnesylated Proteome Using Two-dimensional Electrophoresis Coupled with Western Blotting.
    Date August 2010
    Journal Molecular & Cellular Proteomics : Mcp
    Excerpt

    Prenylation is a post-translational modification critical for the proper function of multiple physiologically important proteins, including small G-proteins, such as Ras. Methods allowing rapid and selective detection of protein farnesylation and geranylgeranylation are fundamental for the understanding of prenylated protein function and for monitoring efficacy of drugs such as farnesyltransferase inhibitors (FTIs). Although the natural substrates for prenyltransferases are farnesyl pyrophosphate and geranylgeranyl pyrophosphate, farnesyltransferase has been shown to incorporate isoprenoid analogues into protein substrates. In this study, protein prenyltransferase targets were labeled using anilinogeraniol, the alcohol precursor to the unnatural farnesyl pyrophosphate analogue 8-anilinogeranyl diphosphate in a tagging-via-substrate approach. Antibodies specific for the anilinogeranyl moiety were used to detect the anilinogeranyl-modified proteins. Coupling this highly effective labeling/detection method with two-dimensional electrophoresis and subsequent Western blotting allowed simple, rapid analysis of the complex farnesylated proteome. For example, this method elucidated the differential effects induced by two chemically distinct FTIs, BMS-214,662 and L-778,123. Although both FTIs strongly inhibited farnesylation of many proteins such as Lamins, NAP1L1, N-Ras, and H-Ras, only the dual prenylation inhibitor L-778,123 blocked prenylation of Pex19, RhoB, K-Ras, Cdc42, and Rap1. This snapshot approach has significant advantages over traditional techniques, including radiolabeling, anti-farnesyl antibodies, or mass spectroscopy, and enables dynamic analysis of the farnesylated proteome.

    Title How Do We Compare? Applying Uk Pay for Performance Indicators to an Australian General Practice.
    Date July 2010
    Journal Australian Family Physician
    Excerpt

    United Kingdom general practitioners receive payment based on their performance in multiple clinical indicators. We set out to apply the same indicators in an Australian general practice to benchmark our performance and to see how much work was required to obtain the data.

    Title Mechanism of Radiosensitization by the Chk1/2 Inhibitor Azd7762 Involves Abrogation of the G2 Checkpoint and Inhibition of Homologous Recombinational Dna Repair.
    Date July 2010
    Journal Cancer Research
    Excerpt

    The median survival for patients with locally advanced pancreatic cancer treated with gemcitabine and radiation is approximately 1 year. To develop improved treatment, we have combined a Chk1/2-targeted agent, AZD7762, currently in phase I clinical trials, with gemcitabine and ionizing radiation in preclinical pancreatic tumor models. We found that in vitro AZD7762 alone or in combination with gemcitabine significantly sensitized MiaPaCa-2 cells to radiation. AZD7762 inhibited Chk1 autophosphorylation (S296 Chk1), stabilized Cdc25A, and increased ATR/ATM-mediated Chk1 phosphorylation (S345 Chk1). Radiosensitization by AZD7762 was associated with abrogation of the G(2) checkpoint as well as with inhibition of Rad51 focus formation, inhibition of homologous recombination repair, and persistent gamma-H2AX expression. AZD7762 was also a radiation sensitizer in multiple tumor xenograft models. In both MiaPaCa-2- and patient-derived xenografts, AZD7762 significantly prolonged the median time required for tumor volume doubling in response to gemcitabine and radiation. Together, our findings suggest that G(2) checkpoint abrogation and homologous recombination repair inhibition both contribute to sensitization by Chk1 inhibition. Furthermore, they support the clinical use of AZD7762 in combination with gemcitabine and radiation for patients with locally advanced pancreatic cancer.

    Title P-fluorophenylalanine-induced Restriction of Ion Uptake and Assimilation by Maize Roots.
    Date June 2010
    Journal Plant Physiology
    Excerpt

    Roots of decapitated maize seedlings (Zea mays L.) were exposed for 12 hours to 1.0 millimolar KNO(3) (98.5 atom per cent (15)N) in the presence and absence (control) of 0.1 millimolar p-fluorophenylalanine (FPA), an analog of the amino acid phenylalanine. FPA decreased nitrate uptake but had little effect on potassium uptake. In contrast, accumulation of both ions in the xylem exudate was greatly restricted. The proportion of reduced (15)N-nitrogen that was translocated at each time was also restricted by FPA. These observations are interpreted as indicating that synthesis of functional protein(s) is required for nitrate uptake and for transport of potassium, nitrate, and reduced-(15)N from xylem parenchyma cells into xylem elements. The effect of FPA on nitrate reduction is less clear. Initially, FPA limited nitrate reduction more than nitrate uptake, but by 8 hours the cumulative reduction of entering nitrate was similar ( approximately 35%) in both control and FPA-treated roots. A relationship between nitrate uptake and nitrate reduction is implied. It is suggested that nitrate influx regulates the proportion of nitrate reductase in the active state, and thereby regulates concurrent nitrate reduction in decapitated maize seedlings.

    Title Artery-to-vein Differences in Nitric Oxide Metabolites Are Diminished in Sepsis.
    Date April 2010
    Journal Critical Care Medicine
    Excerpt

    Nitric oxide deficiency may contribute to microvascular dysfunction in sepsis. Current physiologic paradigms contend that nitrite and/or S-nitrosohemoglobin mediate intravascular delivery of nitric oxide. These nitric oxide metabolites are purportedly consumed during hemoglobin deoxygenation, producing nitric oxide and coupling intravascular nitric oxide delivery with metabolic demand. Systemic nitrite and S-nitrosohemoglobin consumption can be assessed by comparing their concentrations in arterial vs. venous blood. We hypothesized that arterial vs. venous differences in nitrite and S-nitrosohemoglobin are diminished in sepsis and associated with mortality.

    Title Collaborative Care - The Role of Practice Nurses.
    Date January 2010
    Journal Australian Family Physician
    Excerpt

    Comorbid depression can occur with diabetes and heart disease. This article reports on a feasibility study focusing on additional roles for practice nurses in detecting and monitoring depression with other chronic diseases.

    Title Oral Health During Pregnancy.
    Date December 2009
    Journal The Journal of Maternal-fetal & Neonatal Medicine : the Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians
    Excerpt

    OBJECTIVES. To assess how obstetrician-gynecologists address oral health during pregnancy.

    Title Experience with a Low-pressure Colonic Pouch (mainz Ii) Urinary Diversion for Irreparable Vesicovaginal Fistula and Bladder Extrophy in East Africa.
    Date December 2009
    Journal International Urogynecology Journal and Pelvic Floor Dysfunction
    Excerpt

    We report our experience with a low-pressure colonic pouch for urinary diversion in women with irreparable vesicovaginal fistulas and bladder extrophy.

    Title Stage-for-stage Comparison of Definitive Chemoradiotherapy, Surgery Alone and Neoadjuvant Chemotherapy for Oesophageal Carcinoma.
    Date December 2009
    Journal The British Journal of Surgery
    Excerpt

    Definitive chemoradiotherapy (dCRT) has been proposed as an alternative therapy for selected patients with oesophageal cancer. The aim of this study was to determine the outcomes of dCRT, surgery alone, and neoadjuvant chemotherapy followed by surgery (CS) in patients with oesophageal cancer.

    Title Blimp-1/prdm1 Alternative Promoter Usage During Mouse Development and Plasma Cell Differentiation.
    Date November 2009
    Journal Molecular and Cellular Biology
    Excerpt

    The zinc-finger PR domain transcriptional repressor Blimp-1/Prdm1 plays essential roles in primordial germ cell specification, placental, heart, and forelimb development, plasma cell differentiation, and T-cell homeostasis. The present experiments demonstrate that the mouse Prdm1 gene has three alternative promoter regions. All three alternative first exons splice directly to exon 3, containing the translational start codon. To examine possible cell-type-specific functional activities in vivo, we generated targeted deletions that selectively eliminate two of these transcriptional start sites. Remarkably, mice lacking the previously described first exon develop normally and are fertile. However, this region contains NF-kappaB binding sites, and as shown here, NF-kappaB signaling is required for Prdm1 induction. Thus, mutant B cells fail to express Prdm1 in response to lipopolysaccharide stimulation and lack the ability to become antibody-secreting cells. An alternative distal promoter located approximately 70 kb upstream, giving rise to transcripts strongly expressed in the yolk sac, is dispensable. Thus, the deletion of exon 1B has no noticeable effect on expression levels in the embryo or adult tissues. Collectively, these experiments provide insight into the organization of the Prdm1 gene and demonstrate that NF-kappaB is a key mediator of Prdm1 expression.

    Title Eating Disorders and Obstetric-gynecologic Care.
    Date November 2009
    Journal Journal of Women's Health (2002)
    Excerpt

    Disordered eating can have consequences for gynecologic and obstetric patients and fetuses. Amenorrhea, infertility, hyperemesis gravidarum, and preterm birth have been linked to eating disorders (EDs). This study aimed to evaluate obstetrician-gynecologists' ED-related knowledge, attitudes, and practices.

    Title An Expanding Job Description for Blimp-1/prdm1.
    Date November 2009
    Journal Current Opinion in Genetics & Development
    Excerpt

    The master transcriptional regulator Blimp-1/PRDM1 contains an N-terminal PR/SET domain and five C2H2 zinc fingers located near its C-terminus that mediate DNA binding, nuclear import and recruitment of histone modifying enzymes. These activities account for its ability to control cell-fate decisions in the embryo and govern tissue homeostasis in multiple cell types in the adult organism. New experiments demonstrate an increasing degree of complexity associated with Blimp-1/PRDM1 target site selection and its associations with epigenetic modifiers. Our current understanding of how this single unique species within the family of structurally similar PRDM proteins regulates gene expression patterns and governs developmental programmes in different cell lineages is discussed.

    Title The Assessment of Prognosis of Surgically Resected Oesophageal Cancer is Dependent on the Number of Lymph Nodes Examined Pathologically.
    Date October 2009
    Journal Histopathology
    Excerpt

    The prognosis in surgically resected oesophageal carcinoma (OC) is dependent on the number of regional lymph nodes (LN) involved, but no guidance exists on how many LNs should be examined histopathologically to give a reliable pN status. The aim of this study was to determine whether the number of LNs examined after OC resection has a significant effect on the assessment of prognosis.

    Title Cancer Survivorship: History, Quality-of-life Issues, and the Evolving Multidisciplinary Approach to Implementation of Cancer Survivorship Care Plans.
    Date September 2009
    Journal Oncology Nursing Forum
    Excerpt

    To discuss the history of cancer survivorship, related quality-of-life issues, and cancer survivorship care plans (CSCPs).

    Title Considering the Patient-partner Relationship in Cancer Care: Coping Strategies for Couples.
    Date September 2009
    Journal Clinical Journal of Oncology Nursing
    Excerpt

    A cancer diagnosis, regardless of type or site, raises feelings of fear and loss of control in patients and their partners. Being married is associated with lower mortality from a wide range of illnesses, including cancer.However, the quality of marital interactions is a stronger predictor of health outcomes than marital status alone.When people face great life challenges, they attach importance to their intimate partner's behaviors.Trust, a key component of relationship quality, can lend stability as well as emotional and practical support during treatment.This article will examine the results of research focused on patients with cancer and their partners and discuss the effects of a cancer diagnosis on couples.Recommendations for clinical practice include couple behaviors, communication patterns, and coping strategies.In addition, partners should be included in assessment and interventions to improve the quality of care for patients with cancer.

    Title Patient Perceptions of Obstetrician-gynecologists' Practices Related to Hiv Testing.
    Date August 2009
    Journal Maternal and Child Health Journal
    Excerpt

    The objectives of this study were to (1) determine the percentage of obstetrician-gynecologists' patients who have been tested for HIV; (2) examine patient attitudes about HIV testing and patients' knowledge about their own risk status; (3) determine primary reasons patients decline an HIV test; and (4) learn patient recall of how their obstetrician-gynecologists approach the topic of HIV testing.

    Title Combined Anal Sphincteroplasty and Perineal Reconstruction for Fecal Incontinence in Women.
    Date July 2009
    Journal The Journal of the American Osteopathic Association
    Excerpt

    Although success rates are limited, anal sphincteroplasty is commonly used to treat women with fecal incontinence.

    Title Free Iron Ions Decrease Indoleamine 2,3-dioxygenase Expression and Reduce Ifngamma-induced Inhibition of Chlamydia Trachomatis Infection.
    Date July 2009
    Journal Microbial Pathogenesis
    Excerpt

    Interferon-gamma (IFNgamma)-mediated indoleamine 2,3-dioxygenase (IDO) expression, important in innate immunity, immune suppression, and tolerance, can be counteracted by ferrous iron (FeSO(4)). Elevation of intracellular iron levels during stimulation with IFNgamma impeded IFNgamma-induced IDO mRNA and protein expression in HEp-2 cells. Decreased IDO expression was accompanied by decreased tryptophan degradation. Accordingly, IFNgamma-mediated suppressing effects on Chlamydia trachomatis (CT) infection were reduced or even abolished in the presence of FeSO(4). Conversely, lowering intracellular iron levels by deferoxamine (DFO) did not increase IFNgamma-induced IDO expression but potentiated Chlamydia-suppressing effects by lowering intracellular iron availability. Additionally, DFO led to a CT-induced IDO expression in HEp-2 cells not treated with IFNgamma. In summary, this study demonstrates that iron acts as a regulatory element for modulating IDO expression, in addition to its function as an essential element for chlamydial growth. This may represent an important control mechanism of IDO expression at the transcriptional level.

    Title Screening for Down Syndrome: Changing Practice of Obstetricians.
    Date April 2009
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    We sought to assess the impact of American College of Obstetrician and Gynecologists (ACOG) guidelines on the practices and knowledge of obstetricians regarding screening for Down syndrome 1 year later.

    Title Do Rapid 'superbug' Tests Pay Off? Balance the Costs and Benefits of Leading-edge Technology. Interview by Alan Joch.
    Date April 2009
    Journal Materials Management in Health Care
    Excerpt

    As hospitals become increasingly sensitive to the health and financial consequences of health care-associated infections (HAIs), a new generation of molecular-based testing technologies promises to significantly shorten the time required to identify "superbugs" and other bacterial infections. The leading-edge techniques promise to reduce costs by helping hospitals quickly determine which patients to isolate because they carry active methicillin-resistant Staphylococcus aureus (MRSA) infections, for example, or which ones to release from prophylactic isolation because they ultimately tested negative for a dangerous infection. But diagnostic speed comes at a price--the costs to perform molecular tests are significantly higher than conventional methods. This challenges hospitals to balance health care expenses with medical efficacy, says molecular testing veteran Margie Morgan, Ph.D., scientific director at Cedars-Sinai Medical Center, Los Angeles. "The rapid methods can be extreme time savers and possibly help a great deal with the isolation of patients. But some of the tests may cost five times what manual methods might be, so there is a price for seeing so much of a reduction in time," she says.

    Title Non-vanillyl Resiniferatoxin Analogues As Potent and Metabolically Stable Transient Receptor Potential Vanilloid 1 Agonists.
    Date March 2009
    Journal Bioorganic & Medicinal Chemistry
    Excerpt

    A series of non-vanillyl resiniferatoxin analogues, having 4-methylsulfonylaminophenyl and fluorophenyl moieties as vanillyl surrogates, have been investigated as ligands for rat TRPV1 heterologously expressed in Chinese hamster ovary cells. Although lacking the metabolically problematic 4-hydroxy substituent on the A-region phenyl ring, the compounds retained substantial agonist potency. Indeed, the 3-methoxy-4-methylsulfonylaminophenyl analog (1) was modestly (2.5-fold) more potent than RTX, with an EC(50)=0.106 nM. Further, it resembled RTX in its kinetics and pattern of stimulation of the levels of intracellular calcium in individual cells, as revealed by imaging. Compound 1 displayed modestly enhanced in vitro stability in rat liver microsomes and in plasma, suggesting that it might be a pharmacokinetically more favorable surrogate of resiniferatoxin. Molecular modeling analyses with selected analogues provide evidence that the conformational differences could affect their binding affinities, especially for the ester versus amide at the B-region.

    Title Prognostic Significance of Failure to Cross Esophageal Tumors by Endoluminal Ultrasound.
    Date February 2009
    Journal Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus / I.s.d.e
    Excerpt

    SUMMARY: Failure to intubate and cross esophageal tumors by endosonography is reported in as many as 30% of cases and is thought to be associated with an especially poor prognosis. The aim of this study was to audit the above in a large consecutive case series of Endoscopic Ultrasound (EUS) examinations for esophageal cancer performed in a regional specialist cancer network with particular reference to outcome. A consecutive series of 411 patients underwent EUS examination by a specialist radiologist over a period of 9 years. Forty (10%) of patients required dilation, and there was total failure to cross the tumor in 12 patients (2.9%). Failure to traverse the primary tumor was associated with a diagnosis of squamous cell cancer (8 of 12 patients, 66%, rho = -0.182, P = 0.011). Limited staging information was obtained in 7 of these patients, which altered the computed tomography stage in 5 patients (71%, 3 upstaged, 2 downstaged). Six patients received definitive chemoradiotherapy, two patients surgery and four patients palliative chemotherapy. The median and 5-year survival in patients whose tumors were not crossed was 10 months and 28%, respectively, compared with 24 months and 24%, respectively in patients whose tumors were fully assessed. Failure to cross esophageal tumors in practice was far less common than the literature suggests, and esophageal tumor luminal stenosis should no longer be considered a limitation of endosonography.

    Title Gemcitabine Sensitization by Checkpoint Kinase 1 Inhibition Correlates with Inhibition of a Rad51 Dna Damage Response in Pancreatic Cancer Cells.
    Date February 2009
    Journal Molecular Cancer Therapeutics
    Excerpt

    The protein kinase checkpoint kinase 1 (Chk1) has been implicated as a key regulator of cell cycle progression and DNA repair, and inhibitors of Chk1 (e.g., UCN-01 and EXEL-9844) potentiate the cytotoxic actions of chemotherapeutic drugs in tumor cells. We have examined the ability of PD-321852, a small-molecule Chk1 inhibitor, to potentiate gemcitabine-induced clonogenic death in a panel of pancreatic cancer cell lines and evaluated the relationship between endpoints associated with Chk1 inhibition and chemosensitization. Gemcitabine chemosensitization by minimally toxic concentrations of PD-321852 ranged from minimal (<3-fold change in survival) in Panc1 cells to >30-fold in MiaPaCa2 cells. PD-321852 inhibited Chk1 in all cell lines as evidenced by stabilization of Cdc25A; in combination with gemcitabine, a synergistic loss of Chk1 protein was observed in the more sensitized cell lines. Gemcitabine chemosensitization, however, did not correlate with abrogation of the S-M or G2-M checkpoint; PD-321852 did not induce premature mitotic entry in gemcitabine-treated BxPC3 or M-Panc96 cells, which were sensitized to gemcitabine 6.2- and 4.6-fold, respectively. In the more sensitized cells lines, PD-321852 not only inhibited gemcitabine-induced Rad51 focus formation and the recovery from gemcitabine-induced replication stress, as evidenced by persistence of gamma-H2AX, but also depleted these cells of Rad51 protein. Our data suggest the inhibition of this Chk1-mediated Rad51 response to gemcitabine-induced replication stress is an important factor in determining gemcitabine chemosensitization by Chk1 inhibition in pancreatic cancer cells.

    Title United States Obstetrician-gynecologists' Accuracy in the Simulation of Diagnosing Anxiety Disorders and Depression During Pregnancy.
    Date January 2009
    Journal Journal of Psychosomatic Obstetrics and Gynaecology
    Excerpt

    The objective of this study was to examine obstetrician-gynecologists' diagnostic accuracy for mental health issues during pregnancy through utilization of clinical vignettes describing depressive and anxiety symptoms, as well as to explore factors associated with increased diagnostic accuracy and related practice patterns. Questionnaires were mailed to 1193 American College of Obstetricians and Gynecologists Fellows and Junior Fellows. The response rate was 44% after three mailings. Depression was correctly identified by over 90% of respondents, whereas significantly fewer correctly diagnosed panic disorder (55%) and generalized anxiety disorder (32%). Confidence ratings significantly predicted diagnostic accuracy in some cases. Approximately half of respondents reported referring anxiety disordered patients to a mental health professional. There may be an education gap in ob-gyns' diagnostic knowledge of anxiety disorders, which may addressed by increasing physician confidence in diagnosis through increased training.

    Title Workload and Resource Implications of Upper Gastrointestinal Cancer Surgical Centralisation in South East Wales.
    Date December 2008
    Journal Annals of the Royal College of Surgeons of England
    Excerpt

    The aim of this study was to determine whether one specialist unit could manage all patients diagnosed with oesophagogastric cancer in Gwent and Cardiff and Vale NHS Trusts over a 6-month period with regard to workload, resource and training opportunities.

    Title Improving Gemcitabine-mediated Radiosensitization Using Molecularly Targeted Therapy: a Review.
    Date December 2008
    Journal Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
    Excerpt

    In the last three decades, gemcitabine has progressed from the status of a laboratory cytotoxic drug to a standard clinical chemotherapeutic agent and a potent radiation sensitizer. In an effort to improve the efficacy of gemcitabine, additional chemotherapeutic agents have been combined with gemcitabine (both with and without radiation) but with toxicity proving to be a major limitation. Therefore, the integration of molecularly targeted agents, which potentially produce less toxicity than standard chemotherapy, with gemcitabine radiation is a promising strategy for improving chemoradiation. Two of the most promising targets, described in this review, for improving the efficacy of gemcitabine radiation are epidermal growth factor receptor and checkpoint kinase 1.

    Title Depression in Acute Coronary Syndrome: Has the Evidence Been Implemented?
    Date November 2008
    Journal The Australian Journal of Rural Health
    Title Prospective Comparison of Endosonography, Computed Tomography, and Histopathological Stage of Junctional Oesophagogastric Cancer.
    Date November 2008
    Journal Clinical Radiology
    Excerpt

    To assess the strength of agreement between the perceived preoperative stage of Siewert II (oesophagogastric junction) and Siewert III (proximal gastric tumours) as determined by computed tomography (CT) and endoscopic ultrasound (EUS), both alone and in combination, with histopathological stage.

    Title Relationships Among Pain, Sleep Disturbances, and Depressive Symptoms in Outpatients from a Comprehensive Cancer Center.
    Date October 2008
    Journal Oncology Nursing Forum
    Excerpt

    To describe the pain experience of outpatients with cancer and explore the relationships with sleep disturbance, depression, and patient functioning.

    Title The Combination of Epidermal Growth Factor Receptor Inhibitors with Gemcitabine and Radiation in Pancreatic Cancer.
    Date September 2008
    Journal Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
    Excerpt

    PURPOSE: Gemcitabine-radiotherapy is a standard treatment for locally advanced pancreatic cancer. Clinical data have shown that gemcitabine plus erlotinib is superior to gemcitabine alone for advanced pancreatic cancer. Therefore, we investigated the effects of the combination of epidermal growth factor receptor inhibitors with gemcitabine and radiation on a pancreatic cancer model. EXPERIMENTAL DESIGN: EGFR signaling was analyzed by measuring phosphorylated EGFR (pEGFR(Y845, (Y1173)) and AKT (pAKT(S473)) protein levels in pancreatic cancer cell lines and tumors. The effects of scheduling on gemcitabine-mediated cytotoxicity and radiosensitization combined with erlotinib were determined by clonogenic survival. In vivo, the effects of cetuximab or erlotinib in combination with gemcitabine-radiation on the growth of BxPC-3 tumor xenografts were measured. RESULTS: We found in vitro that gemcitabine induced phosphorylation of EGFR at Y845 and Y1173 that was blocked by erlotinib. Treatment of BxPC-3 cells with gemcitabine before erlotinib enhanced gemcitabine-mediated cytotoxicity without abrogating radiosensitization. In vivo, cetuximab or erlotinib in combination with gemcitabine-radiation inhibited growth compared with gemcitabine-radiation (time to tumor doubling: gemcitabine + radiation, 19 +/- 3 days; cetuximab + gemcitabine + radiation, 30 +/- 3 days; P < 0.05, erlotinib + gemcitabine + radiation 28 +/- 3 days; P < 0.1). Cetuximab or erlotinib in combination with gemcitabine-radiation resulted in significant inhibition of pEGFR(Y1173) and pAKT(S473) early in treatment, and pEGFR(Y845), pEGFR(Y1173), and pAKT(S473) by the end of treatment. This study shows a novel difference pEGFR(Y845) and pEGFR(Y1173) in response to EGFR inhibition. CONCLUSIONS: These results show that the EGFR inhibitors cetuximab and erlotinib increase the efficacy of gemcitabine-radiation. This work supports the integration of EGFR inhibitors with gemcitabine-radiation in clinical trials for pancreatic cancer.

    Title Paclitaxel Poliglumex and Carboplatin As First-line Therapy in Ovarian, Peritoneal or Fallopian Tube Cancer: a Phase I and Feasibility Trial of the Gynecologic Oncology Group.
    Date September 2008
    Journal Gynecologic Oncology
    Excerpt

    PURPOSE: To estimate the maximum tolerated dose (MTD) of paclitaxel poliglumex (PPX) in combination with carboplatin in patients with chemotherapy-naive ovarian, primary peritoneal or fallopian tube cancer, and to assess the feasibility of administering multiple cycles of this regimen. METHODS: The first 11 patients were treated in a standard 3 + 3 dose-seeking design, with carboplatin held constant at area under the curve (AUC) of 6 and PPX at 225, 175 or 135 mg/m(2). Pharmacokinetics of PPX and carboplatin were evaluated during this dose-seeking component of the trial. MTD was defined by acute dose-limiting toxicities (DLT) in the first cycle. Twenty additional evaluable patients were treated at the estimated MTD to assess the feasibility of this regimen over >or=4cycles. RESULTS: PPX at 225 mg/m(2) resulted in DLT in 2/3 patients, and was de-escalated first to 175 mg/m(2) and then to 135 mg/m(2). PPX slowly hydrolyzed to paclitaxel and did not alter the pharmacokinetics of carboplatin. DLT within the first 4-cycles were observed in 3 patients (15%) treated at the MTD: neutropenia > 2weeks (2), febrile neutropenia (1). Nineteen patients (95%) experienced grade 4 neutropenia. Sixteen patients (80%) had at least one episode of grade 3 thrombocytopenia. Three patients (15%) had grade 2 and one had grade 3 peripheral neuropathy. Complete response by CA-125 was 75%. CONCLUSIONS: The recommended dose of PPX of 135 mg/m(2) with carboplatin (AUC = 6) in newly diagnosed ovarian cancer was feasible for multiple cycles, but hematologic toxicity was greater compared with standard carboplatin and 3-hour paclitaxel.

    Title Obstetrician-gynecologists' Screening and Management of Preterm Birth.
    Date August 2008
    Journal Obstetrics and Gynecology
    Excerpt

    To define obstetrician-gynecologists' screening for potential preterm birth risk factors and interventions they use when indicators suggest the patient may be at increased risk.

    Title Phase Ii Multicenter Open-label Study of Karenitecin in Previously Treated Epithelial Ovarian and Primary Peritoneal Cancer: a Gynecologic Oncology Group Study.
    Date July 2008
    Journal International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society
    Excerpt

    The topoisomerase I agents are established as a therapy in recurrent ovarian cancer. Karenitecin, an analog of topotecan with solubility and pharmacologic advantages, was tested in a phase II trial in previously treated patients with recurrent or persistent ovarian cancer. The drug was administered intravenously over 1 h at a dose of 1.0 mg/m(2) daily for 5 days every 21 days. Patients were treated until disease progression, intolerable toxicity, or voluntary withdrawal. Response was evaluated according to modified RECIST criteria. Twenty-seven patients were entered into the study. One patient was inevaluable for not receiving any treatment. Of the 26 evaluable patients, there were two partial responses and one complete response for a total response rate of 12%. This response rate was insufficient to justify accrual to the second stage. The most common grade 3 or 4 toxicities were neutropenia (19%) and gastrointestinal (15%). Karenitecin is a well-tolerated topoisomerase compound but has minimal activity in extensively pretreated ovarian cancer with the dose-schedule employed.

    Title Intraperitoneal Chemotherapy for Ovarian Cancer.
    Date July 2008
    Journal Advances in Experimental Medicine and Biology
    Title Obstetrician-gynecologists' Screening Patterns for Anxiety During Pregnancy.
    Date June 2008
    Journal Depression and Anxiety
    Excerpt

    As obstetrician-gynecologists (ob-gyns) take on a greater role in women's healthcare, it is important that they are aware of the high prevalence of anxiety disorders in their patient population. Anxiety disorders present during pregnancy can have detrimental effects on both mother and child. In this study, we queried 1,193 ob-gyns on their screening rates, practice patterns, training, and knowledge as they relate to anxiety disorders during pregnancy. We achieved a 44% response rate (n=397) after three mailings. Physicians reported a moderate interest in screening for and diagnosing anxiety, but less interest in treatment. Only 20% of respondents (n=79) screen for anxiety during pregnancy, and they typically refer anxiety-disordered patients to mental health professionals. Ob-gyns with comprehensive or adequate training were significantly more likely to screen than those who stated that their training was inadequate. Having a friend who has been diagnosed with an anxiety disorder also significantly increased both the likelihood that these physicians would screen and the reported level of interest in screening of anxiety disorders during pregnancy. At present, the majority of ob-gyns feel that their training in this area was barely adequate to inadequate. Specifically, generalized anxiety disorder may be the least understood. Increased training in this area would allow ob-gyns to overcome what they list as the primary barrier to anxiety screening during pregnancy--that is, inadequate training about anxiety disorders.

    Title Obstetrician-gynecologists' Practices Regarding Preterm Birth at the Limit of Viability.
    Date April 2008
    Journal The Journal of Maternal-fetal & Neonatal Medicine : the Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians
    Excerpt

    To assess obstetrician-gynecologists' judgments of gestational age of viability and earliest age of medical intervention for preterm delivery, and to associate these practice decisions with physician characteristics.

    Title Obstetrician-gynecologists' Knowledge of Preterm Birth Frequency and Risk Factors.
    Date March 2008
    Journal The Journal of Maternal-fetal & Neonatal Medicine : the Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians
    Excerpt

    To assess obstetrician-gynecologists' knowledge of preterm birth, including prevalence, risk factors, and utility of various tests in predicting increased risk.

    Title Influence of Socio-economic Deprivation on Outcomes for Patients Diagnosed with Oesophageal Cancer.
    Date March 2008
    Journal Scandinavian Journal of Gastroenterology
    Excerpt

    To determine the influence of deprivation on outcomes for patients with oesophageal cancer.

    Title Stereospecific High-affinity Trpv1 Antagonists: Chiral N-(2-benzyl-3-pivaloyloxypropyl) 2-[4-(methylsulfonylamino)phenyl]propionamide Analogues.
    Date February 2008
    Journal Journal of Medicinal Chemistry
    Excerpt

    Previously, we reported the thiourea antagonists 2a and 2b as potent and high affinity TRPV1 antagonists. For further optimization of the lead compounds, a series of their amide and alpha-substituted amide surrogates were investigated and novel chiral N-(2-benzyl-3-pivaloyloxypropyl) 2-[4-(methylsulfonylamino)phenyl]propionamide analogues were characterized as potent and stereospecific rTRPV1 antagonists. In particular, compounds 72 and 73 displayed high binding affinities, with K i values of 4.12 and 1.83 nM and potent antagonism with K i values of 0.58 and 5.2 nM, respectively, in rTRPV1/CHO cells. These values are comparable or more potent than those of 5-iodoRTX under the same assay conditions. A distinctive binding model that includes two hydrophobic pockets is proposed for this series of compounds based on docking studies of 57 and 72 with a homology model of the TM3/4 region of TRPV1.

    Title Sexual Function in Women After Rectocele Repair with Acellular Porcine Dermis Graft Vs Site-specific Rectovaginal Fascia Repair.
    Date January 2008
    Journal International Urogynecology Journal and Pelvic Floor Dysfunction
    Excerpt

    The objective of the study was to compare preoperative and postoperative sexual function between women undergoing rectocele repair with porcine dermis graft and women undergoing site-specific repair of rectovaginal fascia. A standardized, validated questionnaire (Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire [PISQ]) was used to collect preoperative sexual function data from 100 patients with rectocele pelvic organ prolapse quantification stage 2 or greater. Fifty women underwent rectocele repair utilizing porcine dermis graft (group 1) and 50 women underwent a site-specific repair of the rectovaginal fascia (group 2). The same questionnaire was administered to all subjects 6 months after surgery. The two groups were similar in age, race, parity, prior hysterectomy, and postmenopausal hormone use. Preoperative sexual function scores were similar in the two groups (group 1 81.4+/-7.3 and group 2: 83.6+/-8.2, p=1.0). Six months after surgery, PISQ scores in group 1 significantly increased (score increase 19.9+/-2.2, p=0.01). The mean increase in PISQ scores for group 2 was 6.9+/-3.1 (p=0.08). When compared with group 2, subjects undergoing rectocele repair with porcine dermis graft scored significantly higher on the PISQ 6 months after surgery (group 1 101.3+/-6.4 and group 2 89.7+/-7.1, p=0.01). We conclude that rectocele repair using porcine dermis graft is associated with improved sexual functioning when compared with site-specific rectovaginal fascia repair.

    Title Prospective Cohort Comparison of Neoadjuvant Chemoradiotherapy Versus Chemotherapy in Patients with Oesophageal Cancer.
    Date December 2007
    Journal The British Journal of Surgery
    Excerpt

    Chemotherapy and chemoradiotherapy are common neoadjuvant treatments for resectable T3 N0-1 M0 oesophageal carcinoma. The aim of this study was to compare the outcomes of these therapies in consecutive cohorts of patients.

    Title Obstetrician Gynecologists' Knowledge and Practice Regarding Human Immunodeficiency Virus Screening.
    Date December 2007
    Journal Obstetrics and Gynecology
    Excerpt

    To gather more information regarding prenatal human immunodeficiency virus (HIV) testing by examining the practice patterns of obstetrician-gynecologists.

    Title Prospective Comparison of Transthoracic Versus Transhiatal Esophagectomy Following Neoadjuvant Therapy for Esophageal Cancer.
    Date September 2007
    Journal Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus / I.s.d.e
    Excerpt

    Transthoracic esophagectomy (TT) has been championed as a better cancer operation than transhiatal esophagectomy (TH) because the approach facilitates meticulous wide tumor excision and lymphadenectomy. However, neoadjuvant chemoradiotherapy (CRTS) and chemotherapy (CS) have been reported to improve outcomes, and we aimed to compare outcomes after multimodal therapy related to the operative approach. One hundred and fifty-one consecutive patients were studied prospectively. All patients were staged with computed tomography and endoluminal ultrasound, and treatment decisions were related to stage and performance status. One hundred and nineteen TT (median age 58 years, 92 male, 54 CRTS, 65 CS) were performed compared to 32 TH (median age 57 year, 27 male, 14 CRTS, 18 CS). Primary outcome measure was survival. Post-operative morbidity and mortality were 54% and 4%, respectively, after TT compared with 59% and 6% after TH (chi2 0.239 df 1, P=0.625). Recurrent cancer was no less frequent after TT (52%) than after TH (37.5%, chi2 2.151 df=1, P=0.142). Cumulative uncorrected 5-year survival was 34% after TT compared with 53% after TH (log rank 1.44, df=1, P=0.2298). Median survival was also similar in lymph node positive patients (TT vs. TH, 23 months vs. 22 months, respectively, log rank 0.25, df=1, P=0.6199). Despite the fact that patients receiving multimodal therapy and a TH esophagectomy were less fit, operative morbidity, mortality and recurrence were similar, and survival did not differ significantly when compared with multimodal TT esophagectomy.

    Title Targeting Vascular Endothelial Growth Factor (vegf)-receptor-signaling in Renal Cell Carcinoma.
    Date August 2007
    Journal World Journal of Urology
    Excerpt

    Metastatic renal cell carcinoma (RCC) is resistant to conventional chemotherapy. Combined data for a variety of immunotherapies resulted in an overall chance of partial (PR) or complete remission (CR) of only 12.9%. There is a clear need for novel, more effective therapies to prevent relapse, control metastases and improve overall survival. Improved understanding of RCC disease biology has led to the introduction of molecularly targeted treatment strategies in these cancers. Von Hippel-Lindau (VHL) gene inactivation is observed in most clear cell renal carcinoma, resulting in vascular endothelial growth factor (VEGF) over-expression and driving the malignant phenotype. This review discusses the efficacy of novel therapies targeting the VEGF receptor (VEGFR) (e.g. anti-VEGF antibodies, VEGFR tyrosine kinase inhibitors, mTOR inhibitors), some of which were recently approved by the Food and Drug Administration/European Medicines Evaluation Agency (FDA/EMEA) and represent the new treatment standards in RCC patients.

    Title Staining of Chlamydia Trachomatis Elementary Bodies: a Suitable Method for Identifying Infected Human Monocytes by Flow Cytometry.
    Date July 2007
    Journal Journal of Microbiological Methods
    Excerpt

    Persistence of Chlamydia trachomatis (C. trachomatis) in the joint is the most frequent cause of reactive arthritis following urogenital tract infection. The resulting changes of host cell antigen- and cytokine-expression are not precisely understood. We developed and evaluated a direct cytometric approach to visualize in vitro C. trachomatis-infected monocytes. Infectious elementary bodies (EBs) of C. trachomatis serovar K were labelled by incubation with 5-(and-6)-carboxyfluorescein diacetate succinimidyl ester (CFSE). Afterwards, human peripheral blood monocytes were cultured with the CFSE-labelled EBs and analysed by flow cytometry. Real-time polymerase chain reaction (PCR) was used to demonstrate intracellular uptake and viability of CFSE-labelled C. trachomatis by the determination of gene expression. Labelling EBs with CFSE may become a valuable tool for studying the interaction between C. trachomatis and the host cell.

    Title Another View of "humanitarian Ventures" and "fistula Tourism".
    Date July 2007
    Journal International Urogynecology Journal and Pelvic Floor Dysfunction
    Excerpt

    There are many ethical issues involved in medical missions to developing countries. The Current Opinion/Update "Humanitarian ventures or 'fistula tourism?': the ethical perils of pelvic surgery in the developing world" raised many concerns about surgical trips to treat obstetric fistula. Despite a lack of experience with obstetric fistula, western surgeons may still bring surgical and public health techniques that may be of value to health systems in developing countries. Emphasis should be placed on program development and assessment first. This should include not only surgical training but also help with counseling, prevention and reintegration. Participation in clinical trials should be up to the health care personnel in the country being helped, and aide should not depend on such participation. Success will likely be determined by a national effort and integration into existing health systems, not isolated "fistula champions." The appalling situation of obstetric fistula in the twenty-first century should be a wake-up call to obstetricians/gynecologists and urologists. The dictum "first do no harm" must not evolve into "first do nothing."

    Title Interactions of Doctors with the Pharmaceutical Industry.
    Date June 2007
    Journal Journal of Medical Ethics
    Excerpt

    To assess the opinions and practice patterns of obstetrician-gynaecologists on acceptance and use of free drug samples and other incentive items from pharmaceutical representatives.

    Title Risk of Colorectal Cancer in Women with a Prior Diagnosis of Gynecologic Malignancy.
    Date June 2007
    Journal Journal of Clinical Gastroenterology
    Excerpt

    GOALS AND BACKGROUND: Earlier studies regarding the risk of colorectal cancer (CRC) in women with a prior diagnosis of gynecologic malignancies have revealed conflicting results. We sought to further clarify this association. METHODS: A retrospective cohort study was performed using the General Practice Research Database of the United Kingdom. Patients with a prior diagnosis of ovarian, uterine, or cervical cancers were compared with control patients without a prior gynecologic malignancy. The primary outcome was a diagnosis of CRC. Poisson regression analysis was used to assess the effects of potential confounders. RESULTS: The study included 1995 ovarian, 1348 uterine, and 1101 cervical cancer patients and 7980, 5392, and 4404 matched control patients, respectively. The adjusted incidence rate ratio (IRR) of CRC among ovarian cancer patients was 2.90 [95% confidence intervals (CI) 1.45-5.82]. Five of 10 cases of CRC in ovarian cancer patients were diagnosed within 6 months of the cancer diagnosis with an adjusted IRR of 8.0 (95% CI 1.9-33.6). Excluding the initial 6 months of follow-up after the diagnosis of ovarian cancer, the adjusted IRR was 1.6 (95% CI 0.76-5.03). The adjusted IRR of CRC in patients with a prior diagnosis of uterine and cervical cancer was 0.79 (95% CI 0.24-2.61) and 1.50 (95% CI 0.43-5.21), respectively. CONCLUSIONS: Women with a prior diagnosis of ovarian cancer are at an increased risk of CRC. The risk of CRC was not increased among patients with a prior history of uterine and cervical cancer.

    Title Targeting the Ras Signaling Pathway in Malignant Hematologic Diseases.
    Date May 2007
    Journal Current Drug Targets
    Excerpt

    Molecularly targeting signaling pathways that are involved in the pathogenesis of hematopoietic malignancies may lead to more specific and efficacious therapies. Activation of the RAS signal transduction cascade is a common feature in the molecular pathogenesis of hematologic malignancies. A number of novel agents targeting RAS signaling have been developed over the past decade. This review will focus on these agents, which include inhibitors of RAS post-translational modification (farnesyl transferase (FTase)-, geranylgeranyl transferase-I (GGTase-I)-, isoprenylcysteine carboxylmethyltransferase (ICMTase)-inhibitors, statins, bisphosphonates), and inhibitors of RAF and MEK activity. Although some of these inhibitors (e.g. FTase, RAF and MEK inhibitors) were developed to specifically inhibit RAS signaling, it has become clear that RAS may not be the only critical target of these compounds. This review provides a background on RAS signaling in hematologic malignancies and discusses opportunities to exploit aberrant cancer cell signaling in order to develop better treatment options for patients suffering from these diseases.

    Title What Obstetrician-gynecologists Think of Preconception Care.
    Date May 2007
    Journal Maternal and Child Health Journal
    Excerpt

    To describe obstetrician-gynecologists' opinions of preconception care (PCC) and ascertain patient uptake for this service.

    Title Prognostic Significance of Body Mass Indices for Patients Undergoing Esophagectomy for Cancer.
    Date May 2007
    Journal Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus / I.s.d.e
    Excerpt

    The aim of this study was to determine the role of body mass index (BMI) in a Western population on outcomes after esophagectomy for cancer. Two hundred and fifteen consecutive patients undergoing esophagectomy for esophageal cancer of any cell type were studied prospectively. Patients with BMIs > 25 kg/m were classified as overweight and compared with control patients with BMIs below these reference values. Ninety-seven patients (45%) had low or normal BMIs, 86 patients (40%) were overweight, and a further 32 (15%) were obese. High BMIs were associated with a higher incidence of adenocarcinoma versus squamous cell carcinoma (83%vs. 14%, P = 0.041). Operative morbidity and mortality were 53% and 3% in overweight patients compared with 49% (P = 0.489) and 8% (P = 0.123) in control patients. Cumulative survival at 5 years was 27% for overweight patients compared with 38% for control patients (P = 0.6896). In a multivariate analysis, age (hazard ratio [HR] 1.492, 95% CI 1.143-1.948, P = 0.003), T-stage (HR 1.459, 95% CI 1.028-2.071, P = 0.034), N-stage (HR 1.815, 95% CI 1.039-3.172, P = 0.036) and the number of lymph node metastases (HR 1.008, 95% CI 1.023-1.158, P = 0.008), were significantly and independently associated with durations of survival. High BMIs were not associated with increased operative risk, and long-term outcomes were similar after R0 esophagectomy.

    Title Targeting Egf-receptor-signalling in Squamous Cell Carcinomas of the Head and Neck.
    Date March 2007
    Journal British Journal of Cancer
    Excerpt

    Despite significant advances in the use of surgery, chemotherapy and radiotherapy to treat squamous cell carcinoma of the head and neck (SCCHN), prognosis has improved little over the past 30 years. There is a clear need for novel, more effective therapies to prevent relapse, control metastases and improve overall survival. Improved understanding of SCCHN disease biology has led to the introduction of molecularly targeted treatment strategies in these cancers. The epidermal growth factor receptor (EGFR) is expressed at much higher levels in SCCHN tumours than in normal epithelial tissue, and EGFR expression correlates with poor prognosis. Therefore, much effort is currently directed toward targeting aberrant EGFR activity (e.g. cell signalling) in SCCHN. This review discusses the efficacy of novel therapies targeting the EGFR (e.g. anti-EGFR antibodies and EGFR tyrosine kinase inhibitors) that are currently tested in SCCHN patients.

    Title A Case of Vancomycin-resistant Enterococcus Conjunctivitis and Its Clinically Successful Topical Treatment.
    Date March 2007
    Journal Cornea
    Excerpt

    PURPOSE: To describe what is, to our knowledge, the first documented case of vancomycin-resistant enterococcus (VRE) conjunctivitis and its successful topical treatment. METHODS: A 77-year-old white man with end-stage multiple myeloma was hospitalized for congestive heart failure and pneumonia. During hospitalization, the patient developed conjunctivitis. Cultures of the eye were directly plated into several media. The bacterium was tested for antibiotic minimum inhibitory concentration (MIC) with the Clinical and Laboratory Standards Institute (CLSI) method. RESULTS: Culture of the affected eye grew Enterococcus faecalis resistant to vancomycin. Topical treatment with moxifloxacin 0.5% (Vigamox; Alcon, Ft. Worth, TX) resulted in clinical resolution despite a MIC showing resistance. CONCLUSION: Clinical resolution of VRE conjunctivitis was shown with topical moxifloxacin therapy in this case. At the same time, we suggest the use of combined topical and systemic therapy for treatment of VRE in immunocompromised patients.

    Title Going from Genes to Proteins in Myelodysplastic Syndromes.
    Date February 2007
    Journal Proceedings of the National Academy of Sciences of the United States of America
    Title Monitoring Thyroglobulin in a Sensitive Immunoassay Has Comparable Sensitivity to Recombinant Human Tsh-stimulated Thyroglobulin in Follow-up of Thyroid Cancer Patients.
    Date February 2007
    Journal The Journal of Clinical Endocrinology and Metabolism
    Excerpt

    CONTEXT: Most thyroglobulin (Tg) assays have a sensitivity of 0.5-1 ng/ml. A minority of patients with undetectable T4-suppressed Tg levels have a recombinant human TSH (rhTSH)-stimulated Tg above 2 ng/ml and identifiable residual disease. OBJECTIVE: The objective was to determine whether a Tg assay with improved sensitivity could eliminate the need for rhTSH stimulation when baseline Tg is below 0.1 ng/ml. DESIGN: A retrospective study of two academic endocrine practices was conducted. POPULATION: A total of 194 patients undergoing rhTSH stimulation participated in the study. RESULTS: Of the 80 patients with Tg below 0.1 ng/ml, two (2.5%) had rhTSH-stimulated Tg above 2 ng/ml. One other patient with stimulation to 0.3 ng/ml and negative 123I scan had an ultrasound-detected malignant lymph node resected. None had 131I/123I imaging after rhTSH stimulation suggestive of local recurrence or distant metastasis. If T4-suppressed Tg was 0.1-0.5 or 0.6-2.0 ng/ml, rhTSH Tg was above 2 ng/ml in 24.2 and 82.4%, respectively. CONCLUSIONS: Patients with differentiated thyroid carcinoma and a T4-suppressed serum Tg below 0.1 ng/ml rarely have a rhTSH-stimulated Tg above 2 ng/ml, and none of these patients had 131I or 123I imaging after rhTSH stimulation suggestive of local recurrence or distant metastasis. We recommend monitoring such patients with a T4-suppressed Tg level and periodic neck ultrasonography. An increase in T4-suppressed serum Tg to a detectable level or the appearance of abnormal lymph nodes by physical or ultrasound exam should prompt further investigation.

    Title Relative Value of Repeat Gastric Ulcer Surveillance Gastroscopy in Diagnosing Gastric Cancer.
    Date January 2007
    Journal Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
    Excerpt

    Gastric cancer can present with the endoscopic appearances of a benign gastric ulcer (GU). Opinion remains divided on the need for follow-up of patients diagnosed with GU, and the aim of this study was to examine the long-term outcomes of patients whose GU proved malignant on follow-up gastroscopy.

    Title Cbln1 is Essential for Interaction-dependent Secretion of Cbln3.
    Date January 2007
    Journal Molecular and Cellular Biology
    Excerpt

    Cbln1 and the orphan glutamate receptor GluRdelta2 are pre- and postsynaptic components, respectively, of a novel transneuronal signaling pathway regulating synapse structure and function. We show here that Cbln1 is secreted from cerebellar granule cells in complex with a related protein, Cbln3. However, cbln1- and cbln3-null mice have different phenotypes and cbln1 cbln3 double-null mice have deficits identical to those of cbln1 knockout mice. The basis for these discordant phenotypes is that Cbln1 and Cbln3 reciprocally regulate each other's degradation and secretion such that cbln1-null mice lack both Cbln1 and Cbln3, whereas cbln3-null mice lack Cbln3 but have an approximately sixfold increase in Cbln1. Unlike Cbln1, Cbln3 cannot form homomeric complexes and is secreted only when bound to Cbln1. Structural modeling and mutation analysis reveal that, by constituting a steric clash that is masked upon binding Cbln1 in a "hide-and-run" mechanism of endoplasmic reticulum retention, a single arginine confers the unique properties of Cbln3.

    Title Integration of Egfr Inhibitors with Radiochemotherapy.
    Date January 2007
    Journal Nature Reviews. Cancer
    Excerpt

    Laboratory studies that led to the development of epidermal growth factor receptor (EGFR) inhibitors indicated that such inhibitors would be effective when given to patients with tumours that are driven by activated EGFR. However, initial clinical studies have shown modest responses to EGFR inhibitors when used alone, and it has not yet been possible to clearly identify which tumours will respond to this therapy. As a result, EGFR inhibitors are now used in combination with radiation therapy, chemotherapy and, more recently, with concurrent radiochemotherapy. In general, these clinical trials have been designed without much preclinical data. What do we need to know to make these combinations successful in the clinic?

    Title The Relationship of Premature Mitosis to Cytotoxicity in Response to Checkpoint Abrogation and Antimetabolite Treatment.
    Date December 2006
    Journal Cell Cycle (georgetown, Tex.)
    Excerpt

    Inhibition of one or both of the checkpoint kinases, Chk1 and Chk2, has been proposed as a strategy for improving the efficacy of cytotoxic chemotherapeutic agents in tumor cells. Previous studies have demonstrated that Chk1 inhibition potentiates the cytotoxicity of chemotherapeutic agents in a variety of systems. We designed a study to test whether the simultaneous depletion of Chk1 and Chk2 would sensitize cells to FdUrd- and gemcitabine-induced cytotoxicity to a greater extent than Chk1 depletion alone and to determine the contribution of premature mitosis to cytotoxicity. We found that RNAi-mediated Chk1 depletion enhanced FdUrd- and gemcitabine-mediated cytotoxicity (2- to 3-fold) in Panc-1 and SW620 cells. Furthermore, enhanced cytotoxicity by Chk1 depletion was accompanied by inhibition of FdUrd- or gemcitabine-induced Cdc25A degradation and induction of premature mitotic entry in drug-treated cells. The simultaneous depletion of Chk1 and Chk2 inhibited Cdc25A degradation, induced premature mitotic entry and enhanced cytotoxicity in response to FdUrd and gemcitabine to a similar extent as Chk1 depletion alone. These results imply that Chk2 inhibition has no immediate consequence on survival or cell cycle progression in tumor cells treated with antimetabolites, regardless of their Chk1 status. In addition, these results suggest that premature mitotic entry is a qualitative marker for enhanced antimetabolite-induced cytotoxicity by Chk1 inhibition. The finding that Chk1 inhibition significantly enhanced antimetabolite-induced cytotoxicity supports further investigation and the development of more specific Chk1 inhibitors for use in the clinic.

    Title The Influence of Phosphorylation on the Activity and Structure of the Neuronal Iq Motif Protein, Pep-19.
    Date September 2006
    Journal Brain Research
    Excerpt

    PEP-19 is a 7.6 kDa neuronally expressed polypeptide that contains a single calmodulin-binding IQ motif. The calmodulin-binding activity of several neuronal IQ motif proteins is regulated by phosphorylation of a conserved serine. We propose that the serine residue within the IQ motif of PEP-19 is phosphorylated, and that phosphorylation modifies the activity of PEP-19. Camstatin, a functionally active 25-residue fragment of PEP-19's IQ motif, binds calmodulin and inhibits neuronal nitric oxide synthase. A truncated camstatin-in which the IQ motif serine is the only phosphorylatable residue-was screened against 42 different kinases. Truncated camstatin is selectively phosphorylated by four isoforms of protein kinase C. Furthermore, treatment of full-length PEP-19 with PKCgamma catalyzes phosphorylation of the same serine residue. Fluorescent anisotropy shows that phosphorylation of camstatin inhibits its binding to calmodulin. NMR solution structures indicate that both camstatin and phospho-camstatin exist in similar dynamic turn-like conformations. This suggests that camstatin's greater affinity for calmodulin is due not to a change in the conformation of the phospho-peptide, but rather, to a disruption of hydrophobic interactions between phospho-camstatin and calmodulin caused by the presence of the hydrophilic phosphate group. The H(alpha) chemical shifts and the circular dichroism spectra of the camstatins are consistent with those of "nascent helices". We submit that PEP-19 is a PKC substrate, and that the phosphorylation state of PEP-19 may play a role in the modulation of calmodulin-dependent signaling.

    Title Patient-reported Outcomes for Open Versus Laparoscopic Living Donor Nephrectomy.
    Date August 2006
    Journal Progress in Transplantation (aliso Viejo, Calif.)
    Excerpt

    Rates of living kidney donation have increased dramatically in recent years, in large part because of improved surgical techniques such as laparoscopic nephrectomy.

    Title Candida Kefyr As an Emerging Pathogen Causing Nosocomial Bloodstream Infections in Neutropenic Leukemia Patients.
    Date July 2006
    Journal Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America
    Title Obstetrician-gynecologists and Self-identified Depression: Personal and Clinical.
    Date June 2006
    Journal Depression and Anxiety
    Excerpt

    A survey was designed to explore the effect of obstetrician-gynecologists' subjective awareness of depression in themselves and close family/friends on screening patients for depression and on assessing and treating depression in three scenarios describing hypothetical patients during the adolescence, postpartum, and perimenopausal periods. Questionnaires were mailed to 397 members of the American College of Obstetricians and Gynecologists (ACOG) who participate in the Collaborative Ambulatory Research Network (CARN). Fifty-five percent of the questionnaires were returned. One third of physicians reported having suffered from depression occasionally (28.1%), often (3.8%), or all the time (2.4%) during the past year. Having personally suffered from depression was associated with elevated assessment of depression in the scenarios but not with elevated rates of screening for depression in actual practice, nor with aggressiveness of treatment choices in the scenarios. Awareness that a close friend suffered from depression was not associated with lowered mood as measured, but was associated with increased rates of screening for depression in adolescent, postpartum, and perimenopausal patients, and with elevated assessment of depression and more aggressive treatment practices for depression in hypothetical patients at these three life stages. As such, physicians' practices regarding depression may be influenced by something other than reactivity to their own emotional state.

    Title Saphenous Vein Sparing During Inguinal Lymphadenectomy to Reduce Morbidity in Patients with Vulvar Carcinoma.
    Date April 2006
    Journal Gynecologic Oncology
    Excerpt

    OBJECTIVES: To compare short- and long-term morbidity associated with saphenous vein sparing versus ligation during inguinal lymphadenectomy for vulvar carcinoma. METHODS: A retrospective evaluation of patients with carcinoma of the vulva that underwent inguinal lymphadenectomy was performed. Operative reports were evaluated and patients were divided into those who had sparing of the saphenous vein versus ligation. Postoperative short- and long-term complications were compared between the two groups using Pearson chi squared analysis. RESULTS: There were a total of 49 inguinal lymphadenectomies performed on 29 patients. The saphenous vein was spared in 18 (37%) groin dissections compared to 31(63%) in which the saphenous vein was ligated. The two groups were similar in regards to clinical characteristics. All patients received closed suction drains and prophylactic antibiotics. Median number of nodes dissected was similar. Cellulitis was more common in the vein-ligated group compared to the vein-spared group (45% vs. 0%; P < 0.001). Wound breakdown occurred in 25% of dissections where the saphenous vein was ligated versus 0% in dissections where the vein was spared (P = or < 0.02). Short-term edema (< or = 6 months) was similar between vein-ligated and vein-spared groups (67% vs. 72%, P < 1.0). Subsequently, chronic lymphedema (> 6 months) persisted in 38% of the vein-ligated group compared to 11% in the vein-spared group (P < 0.05). The incidence of recurrent disease was similar in both groups (19.3 % vs. 22.2% P < 0.1). CONCLUSIONS: Routine preservation of the saphenous vein during inguinal lymphadenectomy for vulvar carcinoma may reduce the incidence of wound cellulitis, wound breakdown, and chronic lymphedema.

    Title Molecularly Targeted Therapies in Myelodysplastic Syndromes and Acute Myeloid Leukemias.
    Date April 2006
    Journal Annals of Hematology
    Excerpt

    Although there has been significant progress in acute myeloid leukemia (AML) treatment in younger adults during the last decade, standard induction therapy still fails to induce remission in up to 40% of AML patients. Additionally, relapses are common in 50-70% of patients who achieve a complete remission, and only 20-30% of patients enjoy long-term disease-free survival. The natural history of myelodysplastic syndrome (MDS) is variable, with about half of the patients dying from cytopenic complications, and an additional 20-30% transforming to AML. The advanced age of the majority of MDS patients limits the therapeutic strategies often to supportive care. To address these shortcomings, much effort has been directed toward the development of novel treatment strategies that target the evolution and proliferation of malignant clones. Presented here is an overview of molecularly targeted therapies currently being tested in AML and MDS patients, with a focus on FMS-like tyrosine kinase 3 inhibitors, farnesyltransferase inhibitors, antiangiogenesis agents, DNA hypomethylation agents, and histone deacetylase inhibitors.

    Title Clinical Approach to Mental Health Issues Among Obstetrician-gynecologists: a Review.
    Date March 2006
    Journal Obstetrical & Gynecological Survey
    Excerpt

    In recent years, obstetrician-gynecologists have taken on a greater role in the provision of primary care. Mental health has been a topic worthy of further exploration as a result of the high prevalence rates of women presenting in gynecologic settings with depressive, anxiety, or eating-disordered symptoms. The detrimental effects of psychopathology have been well documented in the literature, especially if present during pregnancy. This article provides a review of the literature in the area of clinical practice related to mental health among obstetrician-gynecologists based on searches of the Psyc Info and MEDLINE databases. Lack of recognition and underdiagnosis are common problems that need to be addressed by focused educational initiatives. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to recall the importance of screening for various types of mental disease during an ob/gyn visit; describe the detrimental effects of psychopathology, especially during pregnancy; and explain the importance of educational initiatives in detecting and treating mental disorders.

    Title Screening for Down Syndrome: Practice Patterns and Knowledge of Obstetricians and Gynecologists.
    Date March 2006
    Journal Obstetrics and Gynecology
    Excerpt

    OBJECTIVE: To assess obstetricians' practice patterns and knowledge regarding screening for Down syndrome. METHODS: A questionnaire was mailed to 1,105 American College of Obstetricians and Gynecologists Fellows and Junior Fellows in 2004. RESULTS: Sixty percent of questionnaires were returned. Statistical analyses were limited to the 532 practicing obstetricians. Greater than 80% felt their training and experience qualified them to counsel patients about genetic issues in pregnancy. However, 45% rated their residency training regarding prenatal diagnosis as barely adequate or nonexistent. American College of Obstetricians and Gynecologists publications were rated by 86% as an important source of information on genetic counseling. Seventy-eight percent of practitioners counsel all obstetric patients about risks for fetal aneuploidy, and 67% provide counseling for heritable genetic abnormalities. Although the majority (99%) offer second-trimester Down syndrome screening, only 55% also offer first-trimester screening for Down syndrome. Almost one half (49%) use the quad screen, and 6% offer integrated first- and second-trimester screening. The majority (88%) routinely offer amniocentesis to patients who are at elevated risk for genetic abnormalities, whereas 44% also offer chorionic villus sampling. Few (2%) perform chorionic villus sampling. CONCLUSION: Most obstetricians manage patients at risk for fetal genetic abnormalities according to American College of Obstetricians and Gynecologists educational materials. This survey identified deficiencies related to Down syndrome screening, including a limited number of practitioners performing chorionic villus sampling and physicians' own perception that training regarding genetic counseling should be improved. Educational strategies are needed to address these deficiencies before first-trimester screening programs are widely implemented. LEVEL OF EVIDENCE: III.

    Title Women with a Prior Diagnosis of Breast Cancer Are Not at an Increased Risk for Subsequent Colorectal Cancer.
    Date January 2006
    Journal The American Journal of Gastroenterology
    Excerpt

    BACKGROUND: Earlier studies regarding the risk of colorectal cancer in women with a prior diagnosis of breast cancer yielded conflicting results. METHODS: A retrospective cohort study was performed using the General Practitioner Research Database of the United Kingdom. Women with a prior diagnosis of breast cancer were compared with female control patients without a prior history of breast cancer. The primary outcome was an incident diagnosis of colorectal cancer. Poisson regression analysis was utilized to assess the effects of potential confounder variables. RESULTS: The study included 17,415 breast cancer patients and 69,660 matched control patients with follow-up time in person years of 52,914 and 331,480, respectively. The relative rate of colorectal cancer among breast cancer patients was 0.80 (95% CI 0.56-1.15). The relative rate of colorectal cancer among women exposed and unexposed to tamoxifen were 0.73 (95% CI 0.49-1.08) and 1.81 (95% CI 0.85-3.85), respectively. CONCLUSION: Women with a prior diagnosis of breast cancer are not at an increased risk of colorectal cancer; these women can follow average risk screening guidelines for colorectal cancer.

    Title A Neuroendocrine Mechanism for Sustaining Fear.
    Date January 2006
    Journal Trends in Neurosciences
    Excerpt

    Fear is an adaptive response to recognition of a potentially dangerous event. Glucocorticoids are essential for maintaining a wide variety of behavioral events by their regulation of numerous genes; one such gene encodes corticotrophin-releasing hormone (CRH). CRH is involved in diverse behavioral responses to changing environmental demands. In this review, we focus on one aspect of glucocorticoid regulation of CRH--namely, fear-related responses to diverse classes of adverse events, such as those represented by contextual and cue-specific stimuli. Three extra-hypothalamic forebrain sites appear crucial for fear-related behavioral responses: the amygdala and the bed nucleus of the stria terminalis for sustaining adaptive fear-related behaviors, and the medial prefrontal cortex for modulating fear-related behaviors. Central regulation of CRH by glucocorticoids is important for adaptive and sustained fear-related behaviors, and its aberration is associated with anxiety and depressive disorders.

    Title Single-molecule Spectroscopic Determination of Lac Repressor-dna Loop Conformation.
    Date November 2005
    Journal Biophysical Journal
    Excerpt

    The Escherichia coli lactose repressor protein (LacI) provides a classic model for understanding protein-induced DNA looping. LacI has a C-terminal four-helix bundle tetramerization domain that may act as a flexible hinge. In previous work, several DNA constructs, each containing two lac operators bracketing a sequence-induced bend, were designed to stabilize different possible looping geometries. The resulting hyperstable LacI-DNA loops exist as both a compact "closed" form with a V-shaped repressor and also a more "open" form with an extended hinge. The "9C14" construct was of particular interest because footprinting, electrophoretic mobility shift, and ring closure experiments suggested that it forms both geometries. Previous fluorescence resonance energy transfer (FRET) measurements gave an efficiency of energy transfer (ET) of 70%, confirming the existence of a closed form. These measurements could not determine whether open form or intermediate geometries are populated or the timescale of interconversion. We have now applied single-molecule FRET to Cy3, Cy5 double-labeled LacI-DNA loops diffusing freely in solution. By using multiple excitation wavelengths and by carefully examining the behavior of the zero-ET peak during titration with LacI, we show that the LacI-9C14 loop exists exclusively in a single closed form exhibiting essentially 100% ET.

    Title Analysis of Structure-activity Relationships for the 'b-region' of N-(4-t-butylbenzyl)-n'-[4-(methylsulfonylamino)benzyl]-thiourea Analogues As Trpv1 Antagonists.
    Date November 2005
    Journal Bioorganic & Medicinal Chemistry Letters
    Excerpt

    The structure-activity relationships for the 'B-region' of N-(4-t-butylbenzyl)-N'-[4-(methylsulfonylamino)benzyl]thiourea analogues have been investigated as TRPV1 receptor antagonists. A docking model of potent antagonist 2 with the sensor region of TRPV1 is proposed.

    Title Analysis of Structure-activity Relationships for the 'a-region' of N-(4-t-butylbenzyl)-n'-[4-(methylsulfonylamino)benzyl]thiourea Analogues As Trpv1 Antagonists.
    Date November 2005
    Journal Bioorganic & Medicinal Chemistry Letters
    Excerpt

    The structure-activity relationships for the 'A-region' of N-(4-t-butylbenzyl)-N'-[4-(methylsulfonylamino)benzyl]thiourea analogues have been investigated as TRPV1 receptor antagonists. The 2-halogen analogues showed enhanced antagonism compared to the prototype antagonist.

    Title Neonatal Encephalopathy and Cerebral Palsy Revisited: the Current State of Knowledge and the Impact of American College of Obstetricians and Gynecologists Task Force Report.
    Date November 2005
    Journal Journal of Perinatology : Official Journal of the California Perinatal Association
    Excerpt

    OBJECTIVES: To re-assess obstetrician-gynecologists' knowledge of neonatal encephalopathy and cerebral palsy after publication of the ACOG/AAP Task Force report. STUDY DESIGN: A questionnaire investigating knowledge of neonatal encephalopathy and cerebral palsy was mailed to 1060 members of ACOG, 337 of whom participated in a similar study in 2001. RESULTS: There was a strong association between familiarity with ACOG documentation and knowledge of neonatal encephalopathy (NE) and cerebral palsy (CP) (p<0.001). As with obstetricians surveyed in 2001, knowledge gaps remain. Performance was better on practices questions than knowledge questions. About one-third (34.2%) of the physicians said their knowledge of neonatal encephalopathy was poor or deficient; the majority (76%) rated their residency training as inadequate to marginal. CONCLUSION: The results indicate better knowledge of neonatal encephalopathy and cerebral palsy among physicians more familiar with the Task Force report. There is a clear need for emphasis on these topics during training and continuing medical education.

    Title Combining Prenylation Inhibitors Causes Synergistic Cytotoxicity, Apoptosis and Disruption of Ras-to-map Kinase Signalling in Multiple Myeloma Cells.
    Date October 2005
    Journal British Journal of Haematology
    Excerpt

    The high incidence of activating RAS mutations, coupled with accumulating evidence linking RAS to multiple myeloma (MM) pathogenesis, indicate that novel therapies utilising inhibitors of RAS prenylation and signalling may be successful in the management of this disease. While preclinical studies investigating prenylation inhibitors, such as lovastatin, farnesyltransferase inhibitors (FTI) and geranylgeranyltransferase inhibitors (GGTI), have been promising, recent phase I/II clinical trials with FTI R115777 were disappointing, suggesting resistance to FTI monotherapy. To address this issue, the effects of FTI, GGTI and lovastatin alone and in combination were analysed in MM cell lines and primary cells. FTI treatment blocked H-RAS processing, but was ineffective at inhibiting K- and N-RAS prenylation because of alternative geranylgeranylation of these isoforms. However, combinations of FTI and GGTI or lovastatin were found to synergistically inhibit MM cell proliferation, migration, K- and N-RAS processing, RAS-to-mitogen-activated protein kinase signalling and to induce apoptosis. In contrast to FTI, lovastatin and some GGTI were found to cause intracellular accumulation of Rho proteins. Our results suggest that clinical efficacy of prenylation inhibitors in MM are limited by alternative prenylation of several small G-proteins, such as RhoB, K- and N-RAS. Furthermore, strategies combining FTI with GGTI or statins may provide greater efficacy in MM treatment.

    Title Role of Checkpoint Kinase 1 in Preventing Premature Mitosis in Response to Gemcitabine.
    Date October 2005
    Journal Cancer Research
    Excerpt

    The deoxycytidine analogue 2',2'-difluoro-2'-deoxycytidine (gemcitabine) is a potent radiation sensitizer in a variety of solid tumors and tumor cell lines. Previous studies have shown that radiosensitization by gemcitabine is accompanied by simultaneous depletion of dATP pools (through ribonucleotide reductase inhibition) and accumulation in the S-phase of the cell cycle. Because of the importance of cell cycle redistribution in gemcitabine-mediated radiosensitization, we investigated the role of checkpoint kinase (Chk) 1 and Chk2 in gemcitabine-induced cell cycle arrest. We hypothesized that gemcitabine might induce Chk1 or Chk2 signal transduction pathways that mediate S-phase arrest. We found that radiosensitizing concentrations of gemcitabine induced accumulation of phosphorylated Chk1 and Chk2 and down-regulation of Cdc25A in BxPC-3 (10 nmol/L), Panc-1 (100 nmol/L), A549 (30 nmol/L), RKO (30 nmol/L), and SW620 (30 nmol/L) cells. Depletion of Chk1 from Panc-1 cells prevented the down-regulation of Cdc25A in response to gemcitabine. Furthermore, Chk1 depletion permitted Panc-1 and SW620 cells treated with gemcitabine to enter mitosis despite incomplete DNA synthesis. However, depletion of neither Chk1 nor Chk2 abrogated the inhibition of DNA synthesis in response to gemcitabine. These results provide evidence that Chk1 negatively regulates entry into mitosis in response to gemcitabine. Furthermore, these data imply that Chk1 acts to coordinate the cell cycle with DNA synthesis, thus preventing premature mitotic entry in gemcitabine-treated cells.

    Title Risk of Irritable Bowel Syndrome and Depression in Women with Interstitial Cystitis: a Case-control Study.
    Date September 2005
    Journal The Journal of Urology
    Excerpt

    PURPOSE: We determined the risk of irritable bowel syndrome and depression in women with interstitial cystitis. MATERIALS AND METHODS: Cases consisted of 46 women with newly diagnosed interstitial cystitis. The control group consisted of 46 women presenting for an annual gynecologic examination. Data were collected using standardized, validated questionnaires. RESULTS: The 2 groups were similar with respect to age, race, parity, previous pelvic surgery and postmenopausal hormone use. Compared with controls patients with interstitial cystitis were more likely to be diagnosed with irritable bowel syndrome (OR 11, 95% CI 2.7 to 52, p <0.001) and depression (OR 3.97, 95% CI 1.17 to 14.1, p <0.05). In the interstitial cystitis group when we compared women with and without depression, we noted that women with depression were significantly more likely to complain of bladder pain, nocturia, abdominal pain and other bowel symptoms. CONCLUSIONS: The association of irritable bowel syndrome and depression appears to be greater in women with interstitial cystitis than in controls. Additionally, it appears that pain of bladder or bowel origin is a significant cause of depression in women with interstitial cystitis.

    Title Oncolytic Hsv Exerts Direct Antiangiogenic Activity in Ovarian Carcinoma.
    Date September 2005
    Journal Human Gene Therapy
    Excerpt

    In the present study, we investigated the ability of replication-restricted herpes simplex virus (HSV) 1716 lacking ICP34.5 to infect endothelium and disrupt tumor vasculature. HSV-1716 efficiently infected and killed mouse endothelial cell lines H5V and MS1 cells, as well as human umbilical vein endothelial cells in vitro. Capillary tube formation by endothelial cells was inhibited by HSV-1716 in vitro and in vivo. Following intratumoral administration of oncolytic HSV-1716, HSV-glycoproteins could be detected in CD31-positive tumor vascular endothelium by immunostaining. Viral DNA was recovered from highly purified microdissected tumor vascular endothelium. Furthermore, endothelium of tumors treated with HSV-1716 exhibited expression of tissue factor, a marker of endothelial damage. Importantly, HSV antigen and DNA were also detected in endothelium distant from foci of active tumor infection. After intravascular inoculation of HSV-1716, viral glycoproteins were detected in association to tumor endothelium, but not vascular endothelium of different organs. Purified tumor endothelial cells showed high proliferative capability and were susceptible to HSV-1716 infection and killing ex vivo while endothelium from normal organs was not. We conclude that oncolytic HSV-1716 exerts direct antiangiogenic effects, which may contribute to the overall therapeutic efficacy of the virus.

    Title Impact of Self-reported Familiarity with Guidelines for Cystic Fibrosis Carrier Screening.
    Date July 2005
    Journal Obstetrics and Gynecology
    Excerpt

    OBJECTIVE: To assess the impact of self-reported familiarity with published guidelines on knowledge, implementation, and opinions of obstetrician-gynecologists regarding carrier screening for cystic fibrosis. METHODS: A questionnaire pertaining to cystic fibrosis screening guidelines was mailed to 1,165 members of the American College of Obstetricians and Gynecologists. RESULTS: Sixty-four percent of questionnaires were returned. Statistical analyses were limited to the 632 respondents whose primary medical specialty was gynecology (GynOnly) or obstetrics and gynecology (ObGyns). More ObGyns had thoroughly read or skimmed the guidelines (67.1%) than had GynOnlys (41.6%). Correctly responding to basic questions regarding cystic fibrosis was associated with having read the guidelines, although responding to a more complex question was not. Familiarity with the guidelines was associated with correctly identifying the recommendations for offering screening, with practice implementation of cystic fibrosis screening, and with self-ratings of qualifications and training to offer screening and to provide counseling. In contrast, familiarity with the guidelines was not associated with ObGyn's opinion that burden of disease is likely to be influential in patient acceptance of screening. Physicians who had thoroughly read the guidelines were more likely to disagree that the cystic fibrosis screening test is too inaccurate to risk influencing reproductive decision making (thoroughly read = 79% disagree, skimmed = 69%, not read = 58%, not heard of it = 50%). CONCLUSION: There was a strong association between self-reported familiarity with the American College of Obstetricians and Gynecologists/American College of Medical Genetics guidelines and physicians' knowledge, implementation, and ratings of training for offering cystic fibrosis carrier screening.

    Title Pelvic Organ Prolapse, Constipation, and Dietary Fiber Intake in Women: a Case-control Study.
    Date June 2005
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    OBJECTIVE: This study was undertaken to determine whether there is an association among pelvic organ prolapse, constipation, and dietary fiber intake. STUDY DESIGN: Sixty consecutive women with prolapse were compared with 30 control women without prolapse. All women completed 2 validated questionnaires to assess constipation and dietary fiber intake. Multivariate analysis was performed. RESULTS: The risk for constipation was greater in women with prolapse than controls (odds ratio 4.03, 95% CI 1.5-11.4). Median insoluble fiber intake was significantly lower in women with prolapse (2.4 g) than controls (5.8 g, P < .01). The increased risk for constipation was reduced but remained significant after controlling for age and insoluble dietary fiber intake (odds ratio 2.9, 95% CI 1.1-13.5). CONCLUSION: Women with pelvic organ prolapse are at a higher risk for constipation than controls. This increased risk for constipation is partially explained by lower intake of dietary insoluble fiber by women with prolapse than controls.

    Title Sexual Function in Women with Pelvic Organ Prolapse Compared to Women Without Pelvic Organ Prolapse.
    Date May 2005
    Journal The Journal of Urology
    Excerpt

    PURPOSE: We compared sexual function in women with pelvic organ prolapse to that in women without prolapse. MATERIALS AND METHODS: We collected sexual function data using a standardized, validated, condition specific questionnaire. The study group consisted of 30 women with pelvic organ prolapse and it was compared with 30 unmatched controls without evidence of prolapse. RESULTS: The 2 groups were similar in age, race, parity and postmenopausal hormone use. Subjects in the study group were more likely to have undergone previous pelvic surgery. Mean total Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire scores +/- SD were lower in the study group compared with controls (81.4 +/- 7.3 vs 106.4 +/- 15.5, p <0.001). In the study group total questionnaire scores in women with prior pelvic surgery were similar to those in women without prior pelvic surgery (79.3 +/- 14.9 vs 82.9 +/- 10.2, p = 0.61). CONCLUSIONS: Pelvic organ prolapse appears to have a significant negative impact on sexual function.

    Title Prevalence of Cytomegalovirus (cmv) Infection Among Neonatal Intensive Care Unit (nicu) and Healthcare Workers.
    Date March 2005
    Journal The Egyptian Journal of Immunology / Egyptian Association of Immunologists
    Excerpt

    CMV is the most common cause of congenital and perinatal infection, most infections are asymptomatic at birth but later on develop handicaps, mainly neurological disturbances. The aim of the present work is to study the prevalence of CMV infection in NICU, to detect possible nosocomial transmission of CMV infection and determine possible risk factors for neonatal CMV infection. This study was carried on 175 neonates in NICU and 19 employees in the same unit. All members of the study were investigated for serum CMV-IgG and IgM by ELISA and CMV - DNA by PCR. The overall prevalence of CMV was 12.57%, 10 (5.71%) had congenital infection, while 12 cases (6.86%) had perinatal infection. In neonates with congenital CMV infection, the prevalence of breast milk feeding, congenital anomalies and blood transfusion were 80%, 30% and 60%, respectively. In neonates with perinatal CMV infection the prevalence of breast milk feeding, congenital anomalies and blood transfusion were 75%, 16.67% and 50%, respectively. On the other hand from the 19 employees, 2 (10.53%) were CMV-DNA positive by PCR, none of them was CMV-lgM positive and all of them were CMV-IgG positive. The risk factors related to CMV infection among neonates in NICU were, low birth weight, congenital anomalies and breast milk feeding, while CMV infection among employee was related to blood transfusion and employment period. In our results there was no statistical correlation between neonates in NICU and employee in the same unit. CMV infections are of more prevalence in premature and low birth weight neonates in NICU. No evidence of nosocomial CMV transmission to employee in NICU.

    Title Conservative Management of Vesicouterine Fistula After Uterine Rupture.
    Date March 2005
    Journal International Urogynecology Journal and Pelvic Floor Dysfunction
    Excerpt

    We report the closure of a vesicouterine fistula with conservative management utilizing an indwelling transurethral Foley catheter. Uterine rupture occurred during a trial of vaginal birth after cesarean section, necessitating an emergency cesarean section. Upon entry into the abdomen, the base of the bladder was noted to be involved in the uterine rupture. The bladder trigone and ureteral orifices appeared normal. A primary, two-layer bladder repair was performed. A cystogram on postoperative day 14 demonstrated a vesicouterine fistula. Conservative management involving bladder drainage for 21 days with a transurethral Foley catheter was successful in closure of the fistula.Vesicouterine fistula, a documented complication of uterine rupture due to attempted vaginal birth after previous cesarean section, can spontaneously resolve with conservative management alone.

    Title A New Questionnaire for Urinary Incontinence Diagnosis in Women: Development and Testing.
    Date March 2005
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    OBJECTIVE: The purpose of this study was to develop a questionnaire for urinary incontinence diagnosis in women and to test its reliability and validity, with incontinence specialists' clinical evaluations as the gold standard. STUDY DESIGN: One hundred seventeen urogynecology outpatients with urinary incontinence symptoms completed the Questionnaire for Urinary Incontinence Diagnosis at enrollment and 1 week and 9 months later. Baseline clinical diagnoses were compared with Questionnaire for Urinary Incontinence Diagnosis diagnoses (criterion validity). Nine-month Questionnaire for Urinary Incontinence Diagnosis change scores were compared across treatment groups (responsiveness). RESULTS: Clinical diagnoses included stress (n = 15), urge (n = 26), and mixed urinary incontinence (n = 72). Internal consistency and test-retest reliability estimates were good. Sensitivity and specificity were 85% (95% CI, 75%, 91%) and 71% (95% CI, 51%, 87%), respectively, for stress urinary incontinence and 79% (95% CI, 69%, 86%) and 79% (95% CI, 54%, 94%), respectively, for urge urinary incontinence. The Questionnaire for Urinary Incontinence Diagnosis correctly diagnosed urinary incontinence type in 80% of subjects. Questionnaire for Urinary Incontinence Diagnosis Stress and Urge scores decreased significantly in treated subjects. CONCLUSION: The Questionnaire for Urinary Incontinence Diagnosis, a new 6-item questionnaire for female urinary incontinence type diagnosis, is reliable and able to diagnose stress urinary incontinence and urge urinary incontinence in a referral urogynecology patient population with accuracy.

    Title Practice Patterns of Obstetrician-gynecologists Regarding Preconception and Prenatal Screening for Cystic Fibrosis.
    Date February 2005
    Journal Genetics in Medicine : Official Journal of the American College of Medical Genetics
    Excerpt

    OBJECTIVE: To assess practices of obstetrician-gynecologists regarding carrier screening for cystic fibrosis (CF). METHODS: A questionnaire investigating practice patterns and opinions pertaining to CF screening was mailed to 1165 members of the American College of Obstetricians and Gynecologists (ACOG), of whom 565 participate in the Collaborative Ambulatory Research Network (CARN) and 600 were randomly selected. RESULTS: Of the questionnaires, 64% were returned. Statistical analyses were limited to the 632 respondents whose primary medical specialty was gynecology (Gyn Only) or obstetrics and gynecology (ObGyn). CARN membership was not a significant factor on any nondemographic measure. Almost one-half of physicians do not ask nonpregnant patients their family history of CF or provide them with information about CF screening. The majority of ObGyns (88.7%) ask obstetric patients their family history of CF, and offer CF carrier screening. Almost two-thirds (65.8%) offer screening to all prenatal patients. Among those ObGyns who selectively offer CF screening to pregnant patients, only 27.4% utilized all of the selection criteria in the guidelines. Liability for not offering screening, familiarity with CF, and the ability to interpret a positive screening test were important physician concerns. CONCLUSION: The results indicate a need for minimizing the complexity of clinical guidelines for population-based genetic screening, prospective assessment of implementation and focused continuing education for providers.

    Title Cranberries and Urinary-tract Health: a Knowledge Assessment of American College of Obstetricians and Gynecologists Fellows.
    Date November 2004
    Journal Journal of Alternative and Complementary Medicine (new York, N.y.)
    Title Multiple Pregnancy: Knowledge and Practice Patterns of Obstetricians and Gynecologists.
    Date September 2004
    Journal Obstetrics and Gynecology
    Excerpt

    OBJECTIVE: We sought to assess knowledge and practices of obstetricians regarding multiple gestation. METHODS: A questionnaire investigating knowledge and practice patterns pertaining to multiple gestation was mailed to randomly selected American College of Obstetricians and Gynecologists (ACOG) Fellows and Junior Fellows in January 2003. Fifty-one percent (589/1,146) of the surveys were returned. RESULTS: Statistical analysis included the responses from 430 practicing obstetricians. More than 60% rated their training regarding management of multiples as adequate. Men (56.5%) were older and had been in practice longer than females. Sixty-two percent of general obstetrician-gynecologists managed twins without input from a maternal-fetal medicine specialist. An understanding of chorionicity was less than anticipated. The majority of practitioners managed twins according to recent ACOG educational materials. They did not use prophylactic cerclage, home uterine-activity monitoring, or tocolytics. Fort-six percent encouraged prophylactic bed rest. The management of breech second twins varied. CONCLUSION: Most obstetricians manage multiples according to current ACOG educational materials independent of maternal-fetal medicine specialists. This survey identified knowledge gaps, specifically in chorionicity, indicating the need to develop educational strategies addressing these insufficiencies.

    Title Fibroblast Growth Factors Regulate Prolactin Transcription Via an Atypical Rac-dependent Signaling Pathway.
    Date June 2004
    Journal Molecular Endocrinology (baltimore, Md.)
    Excerpt

    Fibroblast growth factors (FGFs) play a critical role in pituitary development and in pituitary tumor formation and progression. We have previously characterized FGF signal transduction and regulation of the tissue-specific rat prolactin (rPRL) promoter in GH4 pituitary cells. FGF induction of rPRL transcription is independent of Ras, but mediated by a protein kinase C-delta (PKCdelta)-dependent activation of MAPK (ERK). Here we demonstrate a functional role for the Rho family monomeric G protein, Rac1, in FGF regulation of PRL gene expression via an atypical signaling pathway. Expression of dominant negative Rac, but not RhoA or Cdc42, selectively inhibited FGF-induced rPRL promoter activity. Moreover, expression of dominant negative Rac also attenuated FGF-2 and FGF-4 stimulation of MAPK (ERK). However, in contrast to other Rac-dependent signaling pathways, FGF activation of rPRL promoter activity was independent of the c-Jun N-terminal kinase (JNK) and phosphoinositide 3-kinase/Akt cascades. FGFs failed to activate JNK1 or JNK2, and expression of dominant negative JNK or Akt constructs did not block FGF-induced PRL transcription. Consistent with the role of PKCdelta in FGF regulation of PRL gene expression, activation of the rPRL promoter was blocked by an inhibitor of phospholipase Cgamma (PLCgamma) activity. FGF treatment also induced rapid tyrosine phosphorylation of PLCgamma in a Rac-dependent manner. These results suggest that FGF-2 and FGF-4 activate PRL gene expression via a novel Rac1, PLCgamma, PKCdelta, and ERK cascade, independent of phosphoinositol-3-kinase and JNK.

    Title The Role of Bcl-x(s) in Radiation Sensitivity.
    Date June 2004
    Journal Radiation Research
    Excerpt

    Bcl-X(S) is a pro-apoptosis member of the Bcl2 family that has been shown to induce cell death and enhance chemosensitivity. We have investigated the effect of Bcl-X(S) overexpression on radiation sensitivity. Using a tetracycline-repressible system, we found that removal of tetracycline for 16 h induced Bcl-X(S) and reduced the surviving fraction of NIH 3T3 cells to 25%. However, radiation sensitivity was not significantly affected by Bcl-X(S) expression; the mean inactivation doses for Bcl-X(S) repressed and Bcl-X(S) induced cells were 2.7 +/- 0.3 and 2.3 +/- 0.1 Gy, respectively. We conclude that Bcl-X(S) induces cell death without affecting radiation sensitivity. These results suggest that mitochondrial pathways to apoptosis may not have a significant role in survival after irradiation.

    Title Acute Urinary Retention Caused by a Uterine Leiomyoma: a Case Report.
    Date June 2004
    Journal The Journal of Reproductive Medicine
    Excerpt

    BACKGROUND: Large uterine leiomyomas may cause acute urinary retention from bladder outlet obstruction. CASE: A 46-year-old, premenopausal, multiparous woman presented to a large, urban, university emergency department, where a diagnosis of acute urinary retention from uterine prolapse was made. An indwelling Foley catheter was placed. A week later the patient presented to an urogynecologist's office for evaluation of the prolapse and urinary retention. Physical examination showed an 18-20-week-sized uterus with a posterior lower uterine segment leiomyoma displacing the cervix anteriorly, causing bladder outlet obstruction, and no evidence of pelvic organ prolapse. The obstruction was relieved by total abdominal hysterectomy with bilateral salpingo-oophorectomy. CONCLUSION: A large uterine leiomyoma obstructed the bladder neck and presented as urinary retention.

    Title Estrogens and Non-reproductive Behaviors Related to Activity and Fear.
    Date May 2004
    Journal Neuroscience and Biobehavioral Reviews
    Excerpt

    Estrogens affect a variety of behaviors in addition to sexual responses, some of them related to motor activity and emotional reactivity. This is true in experimental animals and in humans. The literatures on these subjects are confusing because not all of the experimental results point in the same direction. Here we propose the following theoretical suggestion, hoping to account for the variety of reports extant: following the generally arousing effects of estrogens, their hormonal actions on motor activity and fear depend on context. In a safe environment, estrogen treatment causes increased activity. But in a novel environment or in contexts otherwise perceived as threatening, activity is reduced by estrogen, due to the hormone's arousing action, which heightens fear. Many hormone-dependent neural circuits involving several neuropeptides could provide mechanisms for this dynamic. We suggest a causal route could involve the activation of corticotropin releasing hormone gene expression in the brain. In sum, estrogenic effects on arousal states, as manifest differently according to details of the environmental context during behavioral test, could account for some of the discrepancies in the literature.

    Title Ventral Medial Prefrontal Cortex and Emotional Perseveration: the Memory for Prior Extinction Training.
    Date January 2004
    Journal Behavioural Brain Research
    Excerpt

    Several years ago, we found that lesions of ventral medial prefrontal cortex (mPFCv) disrupted performance during the extinction component of a classical fear conditioning task without affecting acquisition performance. We called this emotional perseveration, hypothesizing that mPFCv may normally act to inhibit fear responses to a conditioned stimulus (CS) when the CS no longer signals danger. Subsequent studies have supported this hypothesis, showing that mPFCv is crucial for the memory of prior extinction training. The present study examined the effects of mPFCv lesions made after training. Such lesions resulted in reduced freezing to contextual stimuli and normal responding to the CS presented alone during a retention test. Rats were then subjected to extinction trials (CS without US) over multiple days. In contrast to pre-training lesions, post-training lesions had little effect on extinction rate. All rats were given additional training. Lesioned rats expressed greater fear reactions than controls, indicating that prior extinction was less effective in them. Lesioned rats also showed resistance to extinction during reextinction trials, confirming our earlier finding that lesions made before training weaken the effectiveness of extinction trials. These results suggest three conclusions. First, an intact mPFCv during acquisition may protect the animal from prolonged responding during extinction trials following brain insult. Second, changes in mPFCv may predispose subjects toward enhanced fear reactions that are difficult to extinguish when reexposed to fearful stimuli, due to a diminished capacity to benefit from the fear-reducing impact of prior extinction experience. Third, contextual cues processed by mPFCv may influence extinction performance.

    Title Duty Hours and Pregnancy Outcome Among Residents in Obstetrics and Gynecology.
    Date January 2004
    Journal Obstetrics and Gynecology
    Excerpt

    OBJECTIVE: To assess the present status of resident duty hours in obstetrics and gynecology, identify existing policies concerning work schedules during pregnancy, and evaluate pregnancy outcome in female house officers. METHODS: A questionnaire-based study was administered to residents taking the 2001 Council on Residency Education in Obstetrics and Gynecology examination. RESULTS: More than 90% of the residents reported that their institution had a maternity leave policy. The leave was usually 4-8 weeks long and was paid. Nearly 95% of residents reported that they had to take over the work of residents on maternity leave. Most women residents worked more than 80 hours weekly throughout pregnancy, and few took time off before delivery. Most pregnancies occurred during the fourth year of training and did not seem to be adversely affected by the long work hours. CONCLUSION: This study, performed before the institution of the new Accreditation Council for Graduate Medical Education resident duty hour policies, demonstrated that, although women house officers continued to work more than 80 hours per week during pregnancy, most had a good pregnancy outcome. Nevertheless, there was a higher frequency of preterm labor, preeclampsia, and fetal growth restriction in female residents than in spouses or partners of male residents.

    Title Therapeutic Efficacy of Prenylation Inhibitors in the Treatment of Myeloid Leukemia.
    Date November 2003
    Journal Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.k
    Excerpt

    Farnesyltransferase inhibitors (FTIs) represent a new class of anticancer agents that specifically target post-translational farnesylation of various proteins that mediate several cellular processes such as signal transduction, growth, differentiation, angiogenesis and apoptosis. These compounds were originally designed to block oncogenic RAS-induced tumor growth by impeding RAS localization to the membrane, but it is now evident that FTIs also affect processing of several other proteins. The need for novel therapies in myeloid leukemia is underscored by the high rate of treatment failure due to high incidences of relapse- and treatment-related toxicities. As RAS deregulation is important in the pathogenesis of myeloid leukemias, targeting of RAS signaling may provide a new therapeutic strategy. Several FTIs (eg BMS-214662, L-778,123, R-115777 and SCH66336) have entered phase I and phase II clinical trials in myeloid leukemias. This review discusses recent clinical results, potential combination therapies, mechanisms of resistance and the clinical challenges of toxicities associated with prenylation inhibitors.

    Title Synergistic Cytotoxic Effects in Myeloid Leukemia Cells Upon Cotreatment with Farnesyltransferase and Geranylgeranyl Transferase-i Inhibitors.
    Date November 2003
    Journal Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.k
    Excerpt

    As deregulation of RAS signaling is important in the pathogenesis of myeloid leukemias, molecular targeting of RAS signaling may be a promising therapeutic strategy. Farnesyl transferase inhibitors (FTIs) are the most promising class of these new cancer therapeutics. Several FTIs have entered phase II clinical trials in acute myeloid leukemia (AML). Since geranylgeranylation of K-RAS and N-RAS in the presence of FTIs may represent an important mechanism of FTI resistance, 6 geranylgeranyl transferase-I inhibitors (GGTIs) were screened alone and in combination with FTI for growth inhibition of myeloid leukemia cells. Significant growth inhibition (>70%) in myeloid cell lines was observed for GGTI-286 (9/19), GGTI-298 (14/19), GGTI-2147 (16/19) and FTI L-744,832 (17/17). GGTI treatment of NB-4 cells resulted in an accumulation of cells in G(0)/G(1), whereas FTI L-744,832 primarily caused an increase in G(2)/M. FTI and GGTIs both induced apoptosis. In all cases, FTI/GGTI cotreatment led to synergistic cytotoxic effects in both myeloid cell lines (5/5) and primary AML cells (6/6). This synergy coincided with increased apoptosis. FTI/GGTI cotreatment caused an accumulation of unprocessed N-RAS and inactive N-RAS-RAF complexes. Our results suggest that alternative geranylgeranylation of N-RAS may represent an important mechanism of resistance to FTI monotherapy in myeloid leukemia cells.

    Title Phase Ii Study of Oxaliplatin in Platinum-resistant and Refractory Ovarian Cancer: a Gynecologic Group Study.
    Date September 2003
    Journal Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
    Excerpt

    PURPOSE: A phase II study was conducted to determine the efficacy of oxaliplatin therapy in patients with platinum-resistant or refractory epithelial ovarian carcinoma. MATERIALS AND METHODS: Eligible patients were to receive oxaliplatin 130 mg/m2 intravenously over 2 hours, every 21 days, until progression of disease or adverse effects prohibited further therapy. RESULTS: Of 25 patients entered onto the study, 23 were eligible and assessable. There were no patients with complete response. One patient (4.3%) achieved a partial response, with a response duration of 6.4 months. Nine patients (39.1%) experienced stable disease, with a median duration of 5.6+ months (range, 1.8 to 13.1 months). The most frequently reported drug-related toxicities were hematologic, gastrointestinal, and neurologic. CONCLUSION: Oxaliplatin as a single agent has minimal activity in patients with platinum-resistant or refractory ovarian cancer at the dosage and schedule tested. However, future studies of oxaliplatin combined with other active agents in women with platinum-naïve or platinum-sensitive epithelial ovarian carcinoma may be indicated.

    Title Gene Silencing Mediated by Small Interfering Rnas in Mammalian Cells.
    Date June 2003
    Journal Current Medicinal Chemistry
    Excerpt

    RNA interference (RNAi) as a protecting mechanism against invasion by foreign genes was first described in C. elegans and has subsequently been demonstrated in diverse eukaryotes such as insects, plants, fungi and vertebrates. RNAi is the mechanism of sequence-specific, post-transcriptional gene silencing initiated by double-stranded RNAs (dsRNA) homologous to the gene being suppressed. dsRNAs are processed by Dicer, a cellular ribonuclease III, to generate duplexes of about 21 nt with 3'-overhangs (small interfering RNA, siRNA) which mediate sequence-specific mRNA degradation. In mammalian cells siRNA molecules are capable of specifically silencing gene expression without induction of the unspecific interferon response pathway. Thus, siRNAs have become a new and powerful alternative to other genetic tools such as antisense oligonucleotides and ribozymes to analyze loss-of-function phenotypes. Application of siRNA duplexes to interfere with the expression of a specific gene requires knowledge of target accessibility, highly effective delivery of siRNAs into target cells and for some applications long-term siRNA expression. Effective strategies to deliver siRNAs to target cells in cell culture include transduction by physical or chemical transfection. An alternative strategy uses the endogenous expression of siRNAs by various Pol III promoter expression cassettes that allow transcription of functional siRNAs or their precursors. This review summarizes some genetic and biochemical aspects of RNAi, the delivery and application of siRNAs to target cells, the kinetics of RNAi and the utility of siRNAs as analytical and potential therapeutic tools.

    Title Evaluation of Paclitaxel in Previously Treated Leiomyosarcoma of the Uterus: a Gynecologic Oncology Group Study.
    Date May 2003
    Journal Gynecologic Oncology
    Excerpt

    OBJECTIVE: The purpose of this phase II trial was to evaluate the efficacy of intravenous paclitaxel in patients with recurrent or advanced leiomyosarcoma of the uterus. METHODS: To be eligible, patients with recurrent or persistent leiomyosarcoma of the uterus were to have measurable disease not previously treated with paclitaxel and adequate hematologic (WBC >or=3000/microl, platelet count >or=100000/microl), renal (serum creatinine <or=2.0 mg%), and hepatic (bilirubin <or= 1.5 x institutional normal) functions. Paclitaxel was given at a dose of 175 mg/m(2) (135 mg/m(2) for patients with prior radiotherapy) intravenously over 3 h every 3 weeks. RESULTS: Fifty-three patients were entered on this study; 48 were evaluable for toxicity and response. Fifteen had prior irradiation and 39 had prior chemotherapy. A median of 2 (range: 1-12) courses was given. Grade 4 neutropenia occurred in 3 (6.3%) patients. No grade 4 thrombocytopenia was reported and no deaths were attributable to therapy. Four (8.4%) patients had a complete or partial response and 22.9% had stable disease. CONCLUSIONS: Although toxicity was minimal, this regimen demonstrated modest activity in patients with previously treated advanced or recurrent leiomyosarcoma of the uterus.

    Title Vaginal Erosion After Pubovaginal Sling Procedures Using Dermal Allografts.
    Date January 2003
    Journal The Journal of Urology
    Title Estrogen's Effects on Activity, Anxiety, and Fear in Two Mouse Strains.
    Date June 2002
    Journal Behavioural Brain Research
    Excerpt

    Estrogen has effects on activity levels and emotional reactivity in both humans and rats. In a recent study conducted in ovariectomized (OVX) C57BL/6 (C57) mice we found that treatment with estradiol benzoate (EB) increased anxiety, fear learning, and running wheel activity relative to vehicle control (Veh). The present study was conducted to examine the stability of these findings across mouse strains (C57 and Swiss-Webster; SW), to get a better sense of the magnitude of the anxiety response by reducing baseline anxiety levels, and to discover if EB affects activity levels in a safe environment other than the home-cage running wheel. Mice of both strains treated with EB (s.c. implant, 25 microg in sesame oil, which enters the body over 5 weeks) were more anxious than Veh animals in the open field, elevated plus, and dark-light transition tests. SW animals were less anxious than C57 in the elevated plus. EB-treated animals of both strains were more active in the running wheel than Veh animals, and more active in the test of spontaneous activity in the home cage. EB-treatment also increased fear learning in a step-down avoidance task. EB appears to have a consistent but moderate effect in elevating anxiety and in increasing fear learning in two strains of mice. It is also involved in increasing activity in two different types of locomotion in the safer home cage. We conclude that these results of increased anxiety/fear and increased activity are suggestive of a general increase in arousal, with both sets of responses increasing the likelihood of reproductive behaviors occurring only when the environment predicts success.

    Title Endodermal Cyst of the Oculomotor Nerve.
    Date April 2002
    Journal Neuroradiology
    Excerpt

    Endodermal cysts are rare congenital intracranial lesions. Although histologically benign, they can become symptomatic as a result of mass effect and cause neurological deficits. We report a 30-year-old woman who presented with paresis of her right oculomotor nerve. Magnetic resonance imaging showed a 13 x 8-mm cystic lesion originating from the right oculomotor nerve at its exit from the mesencephalon. She underwent craniotomy, biopsy, slit resection, and drainage of the cyst. To our knowledge, endodermal cysts have not been previously described in relation to the oculomotor nerve.

    Title Phase Ii Trial of Pyrazoloacridine in Recurrent Platinum-resistant Ovarian Cancer: a Gynecologic Oncology Group Study.
    Date March 2002
    Journal American Journal of Clinical Oncology
    Excerpt

    The Gynecologic Oncology Group performed a Phase II study to determine the response rate of pyrazoloacridine (PZA) in patients with platinum-resistant ovarian cancer. PZA was administered at a dose of 750 mg/m2 intravenously over 3 hours every 3 weeks. Among 24 evaluable patients, there was 1 (4.2%) complete and 1 (4.2%) partial response. The major toxicities were hematologic. With the dose and schedule used, PZA had only modest activity in this population.

    Title The Clinical Course of Deep Vein Thrombosis in Patients with Gynecologic Cancer.
    Date January 2002
    Journal Gynecologic Oncology
    Excerpt

    OBJECTIVE: The aim of this study was to evaluate the survival of gynecologic cancer patients diagnosed with deep vein thrombosis. METHODS: We retrospectively reviewed the charts of patients admitted to our institution with gynecologic malignancy who were diagnosed with deep vein thrombosis (DVT) between 1984 and 1995. Data were collected regarding site, stage, histology, treatment, and proximity of DVT to treatment with surgery, chemotherapy, and radiotherapy. This study was limited to cases of ovarian, uterine, and cervical cancer. Descriptive statistics were generated and the survival of patients from the time of DVT was calculated using the Kaplan and Meier method. Cases were then matched by site, stage, histology, and age to controls without DVT to evaluate the effect of DVT on survival. A Cox regression model was used to assess the effect of multiple variables on survival. RESULTS: A total of 74 cases were identified. Ovarian, uterine, and cervical cancer accounted for 45, 27, and 28% of cases, respectively. Approximately 64% of patients had stage III or greater disease. The median survival of all patients from the time of DVT diagnosis was 7.8 months, with only about 20% of patients surviving at 5 years. Patients with cervical cancer or patients who had radiation therapy within 3 months of DVT diagnosis had significantly lessened survival (P < 0.01) than other patients with DVT. The survival of patients from the time of cancer diagnosis with venous thrombosis was significantly worse than a matched control group without DVT (P < 0.001). On multivariate analysis, there was a twofold greater risk of dying in those patients with gynecologic cancer and DVT. CONCLUSION: The development of DVT in conjunction with a gynecologic malignancy connotes a poor prognosis, especially in patients with cervical cancer. It is possible that this poor prognosis is related to the pathophysiology that results in venous thrombosis and not just the presence of cancer.

    Title Effects of Estrogen on Activity and Fear-related Behaviors in Mice.
    Date January 2002
    Journal Hormones and Behavior
    Excerpt

    Estrogen has been shown to affect nonreproductive behaviors in humans and rodents, including anxiety, fear, and activity levels. Rat studies have shown increases and decreases in these behaviors. Inconsistencies may be due to differences in testing conditions and the extent to which each test measures anxiety, fear, or activity. Few mouse studies have been performed. The present study was conducted to address these issues by examining the effect of estradiol benzoate (EB) in ovariectomized (OVX), C57BL/6 mice on a range of behavioral paradigms measuring anxiety [open field (OF), dark-light transition (DLT), elevated plus maze (EP)], activity [running wheel (RW)], and conditioned fear learning (FCon). In OF, vehicle (Veh) animals spent more time in the center than EB-treated animals and were more active overall. In DLT, Veh animals were more active than EB-treated animals in both the dark and light compartments and made more transitions between the two. In EP, Veh animals entered a greater number of arms. During FCon, EB animals froze more than Veh to the conditioned stimulus. In contrast, in the home cage RW, EB animals were more active than Veh. Factor analysis was used to characterize intertask correlations of females' behavior and to explore the possibility that estrogen may have an impact on a general arousal factor. In sum, estrogen treatment heightened fear responses in a range of fear and anxiety-provoking situations (OF, DLT, EP, and FCon), while increasing activity in the safer RW. We suggest that EB treatment may result in a generally more aroused animal.

    Title Human Herpesvirus 6 Limbic Encephalitis After Stem Cell Transplantation.
    Date December 2001
    Journal Annals of Neurology
    Excerpt

    Central nervous system complications are common in stem cell transplant recipients, but selective involvement of the medial temporal area is unusual. The 5 patients reported here presented after stem cell transplantation with increased hippocampal T2 signal on magnetic resonance imaging and increased hippocampal glucose uptake on [F-18]fluorodeoxyglucose-positron emission tomography (FDG-PET) associated with short-term memory loss, insomnia, and temporal lobe electrographic seizure activity. The initial scalp electroencephalograms (EEGs) failed to detect seizure activity in these patients, although the memory dysfunction along with the magnetic resonance imaging and FDG-PET findings suggested subcortical seizure activity. However, extended EEG monitoring revealed repetitive temporal lobe electrographic seizure activity. Follow-up MRIs in 2 patients and postmortem findings on 1 patient suggested that hippocampal sclerosis had developed following the clinical syndrome. Cerebrospinal fluid studies revealed the presence of human herpesvirus 6, variant B, DNA in all of 3 patients who had lumbar punctures. Immunohistochemical staining for the P41 and P101 human herpesvirus 6 protein antigens showed numerous immunoreactive astrocytes and neurons in the hippocampus of 1 of the patients who died from other causes. Because of its subtle clinical presentation, this syndrome may be underrecognized, but can be diagnosed with appropriate magnetic resonance imaging techniques, EEG monitoring, and cerebrospinal fluid viral studies.

    Title Survival of Brca1 Negative Ovarian Cancer Patients Based on Family History.
    Date October 2001
    Journal Gynecologic Oncology
    Excerpt

    OBJECTIVE: To compare survival of ovarian cancer patients with and without a family history of breast or ovarian cancer who are known to be without mutations in BRCA1. METHODS: Patients with ovarian cancer were tested for germline mutations in BRCA1 by polymerase chain reaction amplification of DNA for single-strand conformation polymorphism and direct sequencing analysis to examine the 22 coding exons of BRCA1 in fresh and archived tumor specimens. Demographic and survival data were collected for statistical analysis. Survival data were calculated by the method of Kaplan and Meier and compared by the log-rank test. RESULTS: Of the 110 patients tested at our institution, 100 were noted to be negative for BRCA1 mutations. After exclusion of nonepithelial histologies, benign tumors, primary peritoneal carcinoma, and incomplete staging, 87 patients remained for analysis, of which 37 demonstrated a family history of breast or ovarian cancer. The two groups showed similar age at diagnosis, stage, grade, residual disease, and type of chemotherapy. Median actuarial survival was 75 months for those patients with a family history versus 70 months for those without (P = 0.73). Evaluation of patients with two or more relatives with breast or ovarian cancer also revealed no differences in survival. CONCLUSIONS: Family history of breast or ovarian cancer does not affect survival of patients with ovarian cancer in the absence of mutations in BRCA1. Previously described differences in survival among patients with BRCA1 mutations may be more related to genetic factors than to biases introduced by the presence of family history.

    Title Effects of the Phytoestrogen Coumestrol on Locomotor and Fear-related Behaviors in Female Mice.
    Date September 2001
    Journal Hormones and Behavior
    Excerpt

    Effects of the estrogenic plant isoflavonoid coumestrol (COUM) on locomotor activity and fear-related behaviors in both the absence and the presence of estradiol benzoate (EB) were examined in adult ovariectomized Swiss-Webster mice. In a running wheel paradigm conducted over 10 days, with treatment beginning 12 days prior to testing, daily subcutaneous (sc) injections of 10 microg of COUM did not influence locomotor activity, whereas even the low dose of EB supplied by sc Silastic implant (2.5 microg lasting 5 weeks) produced a significant increase in locomotor activity over animals receiving vehicle alone. In animals receiving both COUM and EB, locomotor activity was significantly diminished compared to the activity observed in animals receiving EB alone. The same animals were also tested in three behavioral paradigms having known activity and fear components (open field, dark/light transition, elevated plus-maze). COUM did not produce significant effects in these assays. However, in an associative fear learning paradigm (fear conditioning), COUM produced significantly less freezing ("fearfulness") in the conditioned fear task than with animals receiving vehicle or a low dose of EB, which did not differ from each other. Unlike EB, which has comparable affinities for estrogen receptor (ER) alpha and ER beta, COUM has a higher affinity for ER beta than for ER alpha. COUM might disrupt estrogen-enhanced locomotor activity by altering the dynamic by which EB acts on the brain through these two ER isoforms. The conditioned fear result suggests that COUM may produce additional effects through alternative pathways.

    Title Lack of Macrophage Fatty-acid-binding Protein Ap2 Protects Mice Deficient in Apolipoprotein E Against Atherosclerosis.
    Date July 2001
    Journal Nature Medicine
    Excerpt

    The adipocyte fatty-acid-binding protein, aP2, has an important role in regulating systemic insulin resistance and lipid metabolism. Here we demonstrate that aP2 is also expressed in macrophages, has a significant role in their biological responses and contributes to the development of atherosclerosis. Apolipoprotein E (ApoE)-deficient mice also deficient for aP2 showed protection from atherosclerosis in the absence of significant differences in serum lipids or insulin sensitivity. aP2-deficient macrophages showed alterations in inflammatory cytokine production and a reduced ability to accumulate cholesterol esters when exposed to modified lipoproteins. Apoe-/- mice with Ap2+/+ adipocytes and Ap2-/- macrophages generated by bone-marrow transplantation showed a comparable reduction in atherosclerotic lesions to those with total aP2 deficiency, indicating an independent role for macrophage aP2 in atherogenesis. Through its distinct actions in adipocytes and macrophages, aP2 provides a link between features of the metabolic syndrome and could be a new therapeutic target for the prevention of atherosclerosis.

    Title Cell-cycle-dependent Activation of Mitogen-activated Protein Kinase Kinase (mek-1/2) in Myeloid Leukemia Cell Lines and Induction of Growth Inhibition and Apoptosis by Inhibitors of Ras Signaling.
    Date April 2001
    Journal Blood
    Excerpt

    Disruption of the RAS-to-mitogen-activated protein kinase (MAPK/ERK) signaling pathway, either directly through activating RAS gene mutations or indirectly through other genetic aberrations, plays an important role in the molecular pathogenesis of myeloid leukemias. Constitutive activation of ERK-1/2 and MEK-1/2, which elicit oncogenic transformation in fibroblasts, has recently been observed in acute myeloid leukemias (AML). In this study, the activation of the RAS-to-MAPK cascade in 14 AML and 5 chronic myeloid leukemia (CML) cell lines is examined and correlated with the effects of a panel of 9 RAS signaling inhibitors on cell viability, colony formation, cell-cycle progression, and induction of apoptosis. Activation of MEK, ERK, and the transcription factors CREB-1, ATF-1, and c-Myc is demonstrated in the majority of the cell lines (9 of 14 AML and 2 of 5 CML cell lines). Although activation of the ERK cascade did not always correlate with the presence of activating RAS mutations or BCR-Abl, it is linked to the G0/G1 and the G2/M phase of the cell cycle. In contrast to most inhibitors (eg, B581, Cys-4-Abs-Met, FPT-2, FTI-276, and FTS), a significant growth inhibition was only observed for FTI-277 (19 of 19), FPT-3 (10 of 19), and the MEK inhibitors U0126 (19 of 19) and PD098059 (8 of 19). Treatment of NB-4 cells with FTI-277 primarily resulted in a G2/M block, whereas treatment with FPT-3 and U0126 led to induction of apoptosis. FTI-277 revealed strong toxicity toward normal purified CD34+ cells. The results suggest differences in the mechanisms of action and support a potential therapeutic usefulness of these inhibitors in the treatment of myeloid leukemias.

    Title Candida Chorioamnionitis After Serial Therapeutic Amniocenteses: a Possible Association.
    Date December 2000
    Journal Journal of Perinatology : Official Journal of the California Perinatal Association
    Excerpt

    BACKGROUND: Reduction amniocentesis is used in cases of severe polyhydramnios to decrease maternal discomfort and the risk of preterm labor. In a MEDLINE search (1966 to present, English language, keywords: amniocentesis, chorioamnionitis), no report of Candida chorioamnionitis after serial reduction amniocentesis exists. CASE: A 29-year-old primigravida with a history of four therapeutic amniocenteses for idiopathic polyhydramnios developed preterm labor at 30 and 5/7 weeks' gestation, rupture of membranes, and Candida albicans chorioamnionitis. Despite aggressive therapy with amphotericin B, the neonate succumbed to overwhelming systemic candidiasis. CONCLUSION: Serial amniocentesis may place patients at elevated risk for Candida chorioamnionitis and subsequent preterm delivery. Clinicians should consider early diagnostic amniocentesis in patients in preterm labor with a history of prior amniocentesis, and the routine Gram stain and culture of amniotic fluid.

    Title Targeting the Ras Signaling Pathway: a Rational, Mechanism-based Treatment for Hematologic Malignancies?
    Date October 2000
    Journal Blood
    Excerpt

    A series of alterations in the cellular genome affecting the expression or function of genes controlling cell growth and differentiation is considered to be the main cause of cancer. These mutational events include activation of oncogenes and inactivation of tumor suppressor genes. The elucidation of human cancer at the molecular level allows the design of rational, mechanism-based therapeutic agents that antagonize the specific activity of biochemical processes that are essential to the malignant phenotype of cancer cells. Because the frequency of RAS mutations is among the highest for any gene in human cancers, development of inhibitors of the Ras-mitogen-activated protein kinase pathway as potential anticancer agents is a very promising pharmacologic strategy. Inhibitors of Ras signaling have been shown to revert Ras-dependent transformation and cause regression of Ras-dependent tumors in animal models. The most promising new class of these potential cancer therapeutics are the farnesyltransferase inhibitors. The development of these compounds has been driven by the observation that oncogenic Ras function is dependent upon posttranslational modification, which enables membrane binding. In contrast to many conventional chemotherapeutics, farnesyltransferase inhibitors are remarkably specific and have been demonstrated to cause no gross systemic toxicity in animals. Some orally bioavailable inhibitors are presently being evaluated in phase II clinical trials. This review presents an overview on some inhibitors of the Ras signaling pathway, including their specificity and effectiveness in vivo. Because Ras signaling plays a crucial role in the pathogenesis of some hematologic malignancies, the potential therapeutic usefulness of these inhibitors is discussed. (Blood. 2000;96:1655-1669)

    Title Can Antenatal Clinical and Biochemical Markers Predict the Development of Severe Preeclampsia?
    Date May 2000
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    OBJECTIVE: This study was undertaken to develop a multivariable clinical predictive rule for severe preeclampsia using second-trimester clinical factors and biochemical markers. STUDY DESIGN: We performed a retrospective cohort study of all pregnant patients with single gestations from 1995 through 1997 for whom we had complete follow-up data. Through medical record review we determined whether patients had severe preeclampsia develop according to American College of Obstetricians and Gynecologists criteria. Case patients with severe preeclampsia were compared with control subjects with respect to clinical data and multiple-marker screening test results. With potential predictive factors identified in the bivariate and stratified analyses both an explanatory logistic regression model and a clinical prediction rule were created. Patients were assigned a predictive score according to the presence or absence of predictive factors, and receiver operating characteristic analysis was used to determine the optimal score cutoff point for prediction of severe preeclampsia with maximal sensitivity. RESULTS: Among the 1998 patients we found 49 patients with severe preeclampsia (prevalence, 2.5%). After we controlled for confounding variables, case patients and control subjects had similar human chorionic gonadotropin and alpha-fetoprotein levels, and the only variables that remained significantly associated with severe preeclampsia were nulliparity (relative risk, 3.8; 95% confidence interval, 1.7-8.3), history of preeclampsia (relative risk, 5.0; 95% confidence interval, 1.7-17.2), elevated screening mean arterial pressure (relative risk, 3.5; 95% confidence interval, 1.7-7.2), and low unconjugated estriol concentration (relative risk, 1.7; 95% confidence interval, 0.9-3.4). Our predictive model for severe preeclampsia, which included only these 4 variables, had a sensitivity of 76% and a specificity of 46%. CONCLUSION: Even after incorporation of the strongest risk factors, our predictive model had only modest sensitivity and specificity for discrimination of patients at risk for development of severe preeclampsia. The addition of the human chorionic gonadotropin and alpha-fetoprotein biochemical markers did not enhance the model's predictive value for severe preeclampsia.

    Title Effect of Thyroid Hormone Administration on Estrogen-induced Sex Behavior in Female Mice.
    Date April 2000
    Journal Hormones and Behavior
    Excerpt

    Effects of thyroid hormones on reproductive processes have been described in sheep, birds, and rats. To extend this subject to mice for eventual analysis with genetically modified animals, we looked for effects of thyroid hormone treatment on lordosis behavior of ovariectomized estrogen-treated female mice. High doses of thyroid hormones reduced lordosis behavior. Since we could not explain this result by pharmacokinetic or peripheral effects, we infer that it worked by a central mechanism. Future investigations must determine whether endogenous fluctuations within the thyroid's normal physiological range have any behavioral effects.

    Title Ultrasonographic Prediction of Fetal Macrosomia. Association with Cesarean Delivery.
    Date March 2000
    Journal The Journal of Reproductive Medicine
    Excerpt

    OBJECTIVE: To investigate whether the incorrect ultrasonographic prediction of macrosomia affects the cesarean delivery rate among nonmacrosomic neonates. STUDY DESIGN: For this retrospective, cohort study, comprehensive ultrasonographic records were reviewed at two centers. Patients with singleton, nonanomalous gestations whose ultrasonography predicted an estimated fetal weight > or = 4,000 g composed one cohort (n = 135), while the other cohort (n = 129) consisted of patients whose ultrasonography predicted an estimated fetal weight between 3,000 and 3,999 g. We compared the cesarean delivery rate in neonates falsely diagnosed with macrosomia (false positives) with the rate in those correctly diagnosed as nonmacrosomic (true negatives). RESULTS: The rate of cesarean delivery was significantly higher among those falsely diagnosed by ultrasonography with a macrosomic fetus as compared to those with a fetus truly diagnosed as nonmacrosomic (42.3% vs. 24.3%, relative risk = 1.74, 95% confidence interval 1.09-2.78). Subgroup analyses excluding diabetic mothers and multiparous women and comparing false positives with true negatives with neonatal birth weights between 3,500 and 4,000 g (birth weights similar to false positives) demonstrated significantly increased cesarean delivery rates among false positives. CONCLUSION: Even in nonmacrosomic neonates, the antenatal ultrasonographic diagnosis of suspected macrosomia is associated with a significant increase in cesarean delivery rates.

    Title Prediction of Delivery Among Women with Early Preterm Labor by Means of Clinical Characteristics Alone.
    Date January 2000
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    OBJECTIVE: This study was undertaken to assess whether individual clinical factors or combinations thereof could be used to accurately predict the risk of delivery within 1 week of admission among women with preterm labor and minimal cervical dilatation. STUDY DESIGN: We performed a case-control study of patients admitted to our institution with preterm labor and minimal cervical dilatation. A case patient was a patient who sought treatment with uterine contractions between 24 and 34 weeks' gestation with cervical dilatation </=2 cm, who received tocolysis with magnesium sulfate, and who was delivered within 7 days of admission. Control subjects were those who had the same presentation with preterm labor but were not delivered within the first 7 days after admission. The medical records of case patients and control subjects were then abstracted, and information on >70 potential predictors was recorded. Statistical analysis consisted of bivariate and multivariable methods. We also generated a multivariable clinical predictive model with the purpose of detecting a proportion as high as possible of those destined to be delivered within 1 week (high sensitivity). We estimated that we would need 50 case patients and 150 control subjects to detect an odds ratio of 2.5 for risk factors with a prevalence of 20%, an alpha error of.05, a beta error of.20, and a control subject/case patient ratio of 3:1. RESULTS: Three variables were eligible for inclusion in our logistic models according to the bivariate analyses-bleeding on admission, substance abuse, and admission white blood cell count >/=14,000 cells/microL. The simplest and most favorable model included only 2 variables, bleeding and substance abuse, and yielded a sensitivity of 46% and a specificity of 76%. The full 3-variable model had similar test characteristics. For no model were we able to achieve a sensitivity >/=50%. CONCLUSION: The results of this case-control study suggest that combinations of clinical factors do not yield an adequate level of discrimination to be used alone for predicting the likelihood of delivery within 1 week among patients with minimal degrees of cervical dilatation.

    Title Contribution of Ventrolateral Prefrontal Cortex to the Acquisition and Extinction of Conditioned Fear in Rats.
    Date December 1999
    Journal Neurobiology of Learning and Memory
    Excerpt

    The ventrolateral, agranular insular portion of prefrontal cortex (PFC) in rats is involved in visceral functions and has been shown to be involved in emotional processes. However, its contribution to aversive learning has not been well defined. Classical fear conditioning has been a powerful tool for illuminating some of the primary neural structures involved in aversive emotional learning. We measured both the acquisition and the extinction of conditioned fear following lesions of the ventrolateral PFC of rats. Lesions reduced fear reactivity to contextual stimuli associated with conditioning without affecting CS acquisition, and had no effect on response extinction. Ventrolateral PFC may normally be involved in the processing of contextual information while not being directly involved in extinction processes within the aversive domain.

    Title Surgical Management of Vulvar Cancer.
    Date October 1999
    Journal Seminars in Surgical Oncology
    Excerpt

    Vulvar cancer is an uncommon disease, marked by typical long delays in diagnosis due to lack of awareness by doctors and patients. The most common histology is squamous, although melanoma, sarcoma and adenocarcinoma occur less frequently. The predictable spread pattern of vulvar cancer to regional then distant lymphatics has allowed for improvements in survival largely due to radical surgical intervention. However, the significant morbidity from radical surgery has led to the search for better prognostic indicators and complementary therapeutic modalities to modify the extent of surgery in both early and advanced disease. En bloc radical vulvectomy and bilateral inguinal-femoral lymphadenectomy are rarely performed today: an early invasive stage has been defined where only limited excision is required. The extent of and the indications for inguinal lymphadenectomy for various clinical tumors and role of separate incisions have been clarified. When disease has spread to more than one inguinal node, adjuvant radiotherapy has replaced pelvic lymphadenectomy as the standard. Inguinal radiotherapy without groin dissection does not appear to be adequate therapy for most patients. The use of chemotherapy and radiation to shrink large tumors to allow surgical resection continues to be evaluated but has demonstrated excellent results to date. The utility of newer techniques of sentinel node mapping is also being evaluated in squamous cancers and melanoma to limit the extent of lymphadenectomy in patients with clinically normally lymph nodes.

    Title Multiple Courses of Antenatal Corticosteroids and Outcome of Premature Neonates. North American Thyrotropin-releasing Hormone Study Group.
    Date October 1999
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    OBJECTIVES: We sought to examine outcome for premature neonates after multiple courses of antenatal corticosteroids compared with a single course. STUDY DESIGN: We performed a post hoc nonrandomized analysis on 710 neonates of 25-32 weeks' gestation who were born to mothers enrolled in the North American Thyrotropin-Releasing Hormone Trial and who received 1, 2, or >/=3 courses of antenatal corticosteroids. RESULTS: There was no detectable clinical difference in incidence of respiratory distress syndrome, chronic lung disease, and intraventricular hemorrhage related to courses of antenatal corticosteroids, and outcome was similar for infants delivered at 7-13 days compared with those delivered at 1-6 days after receiving antenatal corticosteroids. Compared with those who received a single course, neonates who received >/=2 courses had lower birth weights (-39 g, P =.02), and those receiving >/=3 courses had increased risk of death (adjusted odds ratio, 2.8; 95% confidence interval, 1.3-5.9; P =.01) and lower levels of plasma cortisol at age 2 hours. CONCLUSION: In this retrospective analysis multiple courses of antenatal corticosteroids did not improve outcome and were associated with increased mortality, decreased fetal growth, and prolonged adrenal suppression.

    Title Association of Polymorphism Within the Promoter of the Tumor Necrosis Factor Alpha Gene with Increased Risk of Preterm Premature Rupture of the Fetal Membranes.
    Date June 1999
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    The rarer allele of a polymorphism within the promoter region at position -308 of the gene for tumor necrosis factor alpha is associated with increased gene transcription. In this study we tested the hypothesis that this rarer allele is associated with spontaneous preterm birth.

    Title High Deferral Rate for Maternal-neonatal Donor Pairs for an Allogeneic Umbilical Cord Blood Bank.
    Date May 1999
    Journal Transfusion
    Excerpt

    To fully evaluate the safety and efficacy of umbilical cord blood (UCB) as a source of hematopoietic progenitor cells, UCB banks are being established worldwide to provide a readily accessible resource of stem and progenitor cells for allogeneic transplantation. Guidelines for UCB donor criteria have been proposed to minimize the possibility of disease transmission to UCB recipients.

    Title Occult Bilateral Involvement in Stage I Epithelial Ovarian Cancer.
    Date April 1999
    Journal Gynecologic Oncology
    Excerpt

    OBJECTIVE: The aim of this study was to determine the incidence of occult bilateral involvement in Stage I epithelial ovarian cancer. METHODS: We retrospectively reviewed the records of all patients (n = 135) with Stage I epithelial ovarian cancer treated at the University of Pennsylvania Cancer Center between 1985 and 1996. A study group of patients (n = 118) who underwent a bilateral salpingo-oophorectomy as part of their staging laparotomy was identified. Operative notes, pathology reports, and discharge summaries were reviewed to document stage, grade, histology, intraoperative impression, gross pathological description, and microscopic diagnosis. Clinically occult bilateral involvement was defined as pathologically documented ovarian involvement by tumor in an ovary that appeared normal to the surgeon during staging laparotomy. RESULTS: The study group consisted of mostly Stage IA (79/118, 67%), followed by Stage IC (35/118, 30%) and Stage IB (4/118, 3%), tumors. In 9/118 (7.6%) of these cases, bilateral disease was documented in the pathology report. In 3/118 (2.5%) of these cases, the bilateral involvement by tumor was clinically occult at the time of surgery. In only 1/118 (0.85%) of these cases did a clinically abnormal appearing ovary not contain tumor. CONCLUSION: Occult involvement by early ovarian cancer is uncommon at the time of staging laparotomy. In appropriately counseled patients strongly desiring to preserve fertility, a unilateral salpingo-oophorectomy may be considered as part of a staging procedure for apparent Stage IA epithelial ovarian cancer if the contralateral ovary appears normal to the surgeon. Consideration should be given to a wedge biopsy with intraoperative frozen section to help exclude occult disease in the normal appearing ovary.

    Title Predicting Delivery Within 48 Hours in Women Treated with Parenteral Tocolysis.
    Date April 1999
    Journal Obstetrics and Gynecology
    Excerpt

    OBJECTIVE: To develop a prediction rule using clinical admission characteristics for women treated with parenteral tocolysis for preterm labor who are at highest risk of delivery within 48 hours. METHODS: We performed a case-control study of patients treated with magnesium sulfate for idiopathic preterm labor. A case was defined as a patient who received magnesium sulfate tocolysis and delivered within 48 hours of admission. We selected a 48-hour delay to delivery as a clinically relevant endpoint for the maximization of steroid benefit. Controls were patients who received magnesium sulfate tocolysis and remained undelivered 48 hours after admission. Cases and controls were identified by merging a pharmacy billing database with International Classification of Disease codes for premature labor. Medical records were reviewed and risk factor information was obtained. We focused on risk factors within the first hour of admission, because our goal was to identify patients at high risk of delivery early in their hospital course. Backward stepwise logistic regression was used to develop explanatory and predictive models. The focus of the predictive model was to maximize the test's sensitivity and negative predictive value. RESULTS: We identified 50 cases and 150 controls. The following six variables were included in the initial multivariable models based on bivariate analyses: white blood cell count at least 14.0 (1000/microL), cervical dilation at least 2 cm, bleeding, substance abuse, parity, and previous abortion. A two-variable model containing cervical dilation and bleeding had an overall accuracy of 73%, sensitivity of 62%, and specificity of 76%, and it was as sensitive and specific as more complex models. CONCLUSION: Cervical dilation of at least 2 cm and bleeding on admission had an overall accuracy of 73% in predicting the likelihood of delivery within 48 hours in women receiving magnesium sulfate.

    Title Multicenter Evaluation of the Bactec Mgit 960 System for Recovery of Mycobacteria.
    Date March 1999
    Journal Journal of Clinical Microbiology
    Excerpt

    We evaluated the BACTEC MGIT 960 system, which is a fully automated, noninvasive system for the growth and detection of mycobacteria with a capacity to incubate and continuously monitor 960 7-ml culture tubes. We studied 3,330 specimens, 2,210 respiratory and 1,120 nonrespiratory specimens, collected from 2,346 patients treated at six sites. Processed specimens were inoculated into the BACTEC MGIT 960 and BACTEC 460 TB systems, as well as onto Lowenstein-Jensen slants and Middlebrook 7H11/7H11 selective plates. From all culture systems, a total of 362 isolates of mycobacteria were recovered; these were recovered from 353 specimens collected from 247 patients. The greatest number of isolates of mycobacteria (289, or 80% of the 362 isolates) was recovered with the BACTEC MGIT 960, followed by the BACTEC 460 TB (271, or 75%) and solid media (250, or 69%). From all culture systems a total of 132 isolates of Mycobacterium tuberculosis complex were recovered. The greatest number of isolates of M. tuberculosis complex was recovered when liquid medium was combined with conventional solid media; the number recovered with BACTEC 460 TB plus solid media was 128 (97%), that recovered with BACTEC MGIT 960 plus solid media was 121 (92%), that recovered with BACTEC 460 TB was 119 (90%) and that recovered with all solid media combined was 105 (79%). The recovery with BACTEC MGIT 960 alone was 102 (77%). The mean times to detection (TTD) for M. tuberculosis complex were 14.4 days for BACTEC MGIT, 15.2 days for BACTEC 460 TB, and 24.1 days for solid media. The numbers of isolates of Mycobacterium avium complex (MAC) recovered were 172 (100%) for all systems, 147 (85%) for BACTEC MGIT 960, 123 (72%) for BACTEC 460 TB, and 106 (62%) for all solid media combined. The TTD for MAC in each system were 10.0 days for BACTEC MGIT 960, 10.4 days for BACTEC 460 TB, and 25.9 days for solid media. Breakthrough contamination rates (percentages of isolates) for each of the systems were 8.1% for BACTEC MGIT 960, 4.9% for BACTEC 460 TB, and 21.1% for all solid media combined.

    Title Antiphospholipid Antibodies in Chronic Hypertension: the Value of Screening During Pregnancy.
    Date March 1999
    Journal American Journal of Perinatology
    Excerpt

    To determine if screening for antiphospholipid antibodies in gravid chronic hypertension patients is warranted, we performed a retrospective cohort study to test the association between antiphospholipid antibodies and perinatal outcome in this group of women. The primary outcome we compared was adverse perinatal outcome, defined as delivery <37 weeks' gestation secondary to maternal or fetal indications, intrauterine or neonatal death, birth weight <10th percentile for gestational age, early-onset severe preeclampsia, or placental abruption. Our sample size allowed for the detection of a 60% reduction in the relative risk of adverse perinatal outcome in patients who were antiphospholipid antibody screen negative (80% power, P = 0.05). No increased risk of adverse perinatal outcome was demonstrated among patients with positive serum antiphospholipid antibodies (33.3%, 5/15) versus patients with negative screening (40.0%, 22/55) in our cohort (RR 0.88, 95% Cl 0.38-1.83). Furthermore, antiphospholipid antibody status was not associated with adverse perinatal outcome after controlling for classic indications for antibody screening (RRMH 0.63, 95% Cl 0.30-1.33). In conclusion, chronic hypertension patients with positive antiphospholipid antibody screening are not at increased risk for adverse perinatal outcome compared to those with negative screening. Therefore, screening for antiphospholipid antibodies in chronic hypertension patients without classic indications for screening is not warranted.

    Title Allelotype Analysis of Uterine Leiomyoma: Localization of a Potential Tumor Suppressor Gene to a 4-cm Region of Chromosome 7q.
    Date January 1999
    Journal Molecular Carcinogenesis
    Excerpt

    Uterine leiomyoma is a benign smooth muscle tumor of the myometrium and is the most commonly encountered neoplasm in women of reproductive age. As for most benign tumors, the pathogenesis of leiomyoma remains obscure, especially at the molecular genetic level. The purpose of this study was to perform a genome-wide allelotype analysis to identify potential sites of tumor suppressor gene inactivation. Fifty-two cases of uterine leiomyoma were subjected to allelotype analysis by using matched pairs of tumor and blood DNA. Loss of heterozygosity (LOH) was assessed at 61 microsatellite markers distributed throughout the genome and representing all 41 chromosome arms. In general, LOH was very rare except on chromosome 7q, where LOH was observed in 34% of all informative tumors. Fine-deletion mapping with 25 microsatellite markers from the 7q22 region revealed a minimal deletion unit of approximately 4 cM, bounded by the markers D7S2453 proximally and D7S496 distally, that probably harbors a novel tumor suppressor gene involved in the etiology of this tumor.

    Title Recurrence of Gestational Diabetes: Who is at Risk?
    Date November 1998
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    OBJECTIVE: The object was to determine the recurrence rate of gestational diabetes mellitus and to find various risk factors that might increase this rate. STUDY DESIGN: Seventy-eight patients with gestational diabetes mellitus in their index pregnancies were evaluated in subsequent pregnancies. Medical records for the index and subsequent pregnancies were abstracted for age, parity, body mass index, birth weight, gestational age of gestational diabetes mellitus diagnosis, insulin requirement, weight gain, and interval between pregnancies. These variables were then compared between patients with and without gestational diabetes mellitus in their subsequent pregnancies. RESULTS: Fifty-four of 78 patients (69%) had gestational diabetes mellitus in a subsequent pregnancy. The recurrence of gestational diabetes mellitus was more common when the following variables were present in the index pregnancy: parity > or = 1 (P < .004; odds ratio 3.0, 95% confidence interval 1.4-4.8), body mass index > or = 30 kg/m2 (P < .04; odds ratio 3.6, 95% confidence interval 1.1-25.9), gestational diabetes mellitus diagnosis at < or = 24 gestational weeks (P < .0003; odds ratio 20.4, 95% confidence interval 2.5-444), and insulin requirement (P < .0002; odds ratio 2.3, 95% confidence interval 1.3-3.4). A weight gain of > or = 15 pounds (P < .003; odds ratio 2.9, 95% confidence interval 1.0-5.3) and an interval between pregnancies < or = 24 months (P < .03; odds ratio 1.6, 95% confidence interval 1.1-2.2) were also associated with a recurrence of gestational diabetes mellitus. A multiple logistic regression analysis revealed that an interval of < or = 24 months and a weight gain of > or = 15 pounds between pregnancies were most strongly correlated with a recurrence of gestational diabetes mellitus. CONCLUSIONS: Gestational diabetes mellitus is more likely to recur in parous, obese women who had an early gestational diabetes mellitus diagnosis and required insulin in the index pregnancy. In addition, a shorter interval (< or = 24 months) and a larger weight gain (> or = 15 pounds) between pregnancies appear to be the most significant risk factors for a recurrence of gestational diabetes mellitus.

    Title Diagnosis of Fetal Renal Anomalies.
    Date October 1998
    Journal Obstetrics and Gynecology Clinics of North America
    Excerpt

    Urinary tract abnormalities are fairly common in the perinatal period. Ultrasonography is an effective diagnostic tool for identifying fetal urinary tract anomalies and can be helpful in establishing prognosis and guiding treatment decisions. The sonographer is encouraged to characterize and localize the fetal urinary tract abnormality when identified. In doing so, the correct diagnosis can be selected from the differential possibilities, providing vital clinical information needed to develop a care plan for both the pregnant woman and her fetus.

    Title Clinical Characteristics of Clear Cell Carcinoma of the Ovary.
    Date September 1998
    Journal Gynecologic Oncology
    Excerpt

    OBJECTIVE: The aim of this study is to evaluate the clinical characteristics of clear cell carcinoma of the ovary. METHODS: Between 1986 and 1996, 45 patients with clear cell carcinoma of the ovary were identified by scanning the medical records department and the tumor registry at our institution. RESULTS: Median age was 55 years (range 31-80 years). Tumors were 60% (27/45) stage I, 11% (5/45) stage II, 20% (9/45) stage III, and 9% (4/45) stage IV. All patients presented with a pelvic mass ranging in size from 2 x 3 to 20 x 30 cm and all except 1 had optimal cytoreduction. All patients received postoperative platinum-based chemotherapy, 47% (21/45) in combination with paclitaxel. One stage Ia patient refused therapy. Of the 6 stage III/IV patients with measurable residual tumor, 67% (4/6) partially responded to first line chemotherapy by CT scan or second look laparotomy. Recurrences occurred in 37% (10/27) stage I patients, including 18% (2/11) stage Ia, 33% (1/3) stage Ib, and 54% (7/13) stage Ic. Time to recurrence was 16 and 38 months for the two stage Ia patients and 35 months (median, range 18-56 months) for the stage Ic patients. Survival after recurrence was significantly related to disease-free interval after primary chemotherapy. With a median follow-up of 40 months (range 4-145 months), 93% (25/27) of stage I patients are alive, 20% (5/25) with disease, while 46% (6/13) of stage III/IV patients are alive. Median survival for the stage III/IV patients was 22 months (range 4-70 months). CONCLUSIONS: Clear cell tumors of ovary frequently present at early stages. However, these tumors have a propensity for recurrence even after primary chemotherapy in early stage tumors.

    Title Antepartum Cervical Ripening: Applying Prostaglandin E2 Gel in Conjunction with Scheduled Nonstress Tests in Postdate Pregnancies.
    Date September 1998
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    Our purpose was to evaluate whether inserting prostaglandin E2 gel at the time of scheduled nonstress tests in patients with postdate pregnancies can decrease rates of intervention.

    Title The Healthy Neighborhoods Project: a Local Health Department's Role in Catalyzing Community Development.
    Date June 1998
    Journal Health Education & Behavior : the Official Publication of the Society for Public Health Education
    Excerpt

    Studies show that community development approaches to health education may lead not only to improved social, economic, and health status but also to increased individual participation in health education and preventive health care activities. However, because of categorical funding restraints and philosophical issues, local health departments have rarely given control of defining project outcomes to the community. One such project was in a low-income urban neighborhood in the San Francisco Bay Area. In this Healthy Neighborhoods Project, the health department catalyzed community development and organization in a multiethnic public housing complex. As a result, an empowered community successfully advocated to improve public safety by installing street speed humps and increased street lighting. After project completion, residents initiated several additional health actions, including the removal of a neighborhood tobacco billboard. This article describes the project, which may serve as a model for other urban public health programs to explore their role in community empowerment.

    Title Does Cesarean Section Decrease the Incidence of Major Birth Trauma?
    Date May 1998
    Journal Journal of Perinatology : Official Journal of the California Perinatal Association
    Excerpt

    OBJECTIVE: To determine whether the increase in frequency of cesarean section is associated with a decreased incidence of major birth trauma. STUDY DESIGN: A retrospective cohort study was performed evaluating all neonatal cases of major birth trauma from January 1989 to December 1994. Major birth trauma was defined as peripheral plexus or nerve injuries, fractures, or lacerations. The data were grouped into two mutually exclusive periods (January 1989 to December 1990 vs January 1991 to December 1994) in which a significant difference in the cesarean section rate was known. RESULTS: Of 17,957 deliveries during the period, 141 cases of birth trauma occurred. One hundred thirty-seven of the 141 medical records were available for review, and 116 were classified as having had major birth trauma and were included in the study. The overall incidence of major birth trauma was 6.5/1000 deliveries. During the two-year period (January 1989 to December 1990), 18.3% of deliveries were by cesarean section and the major birth trauma rate was 8.4/1000 deliveries. During the following 4 years, the cesarean section rate was 22.3% and the major birth trauma rate was 5.3/1000 deliveries. Significant differences in the birth trauma chi(2) = 6.12, p = 0.013) and cesarean section (chi(2) = 40.80, p < 0.001) rates were observed. Controlling for the mode of delivery lessened the association between time period and birth trauma incidence (chi(2)MH = 3.28, p = 0.07). A significant decrease in the occurrence of major birth trauma in neonates delivered by cesarean section in the later period was discovered (relative risk = 0.46, 95% confidence interval 0.22 to 0.97). This decrease appeared to be mediated by a decrease in total lacerations between the periods (chi(2) = 11.76, p < 0.001), because the rates of other types of major birth trauma did not differ in neonates delivered by cesarean section or the vaginal route. CONCLUSIONS: With a 4% increase in rate of cesarean section at our institution, a significant decrease in the occurrence of major birth trauma was observed. This finding cannot be explained by a decreased risk of neonatal trauma in patients delivering vaginally, but rather by a decreased risk of neonatal trauma at cesarean section during the latter period.

    Title Cortical Blindness and Anton Syndrome in a Patient with Obstetric Hemorrhage.
    Date May 1998
    Journal Obstetrics and Gynecology
    Excerpt

    Cortical blindness is characterized by loss of vision in the presence of intact anterior visual pathways. Anton syndrome, a form of anosognosia, is a rare complication of cortical blindness involving compromise of the visual association centers, with resulting patient denial of blindness. Both syndromes have been associated with computed tomography findings of localized cortical ischemia. In most cases, both the clinical and radiologic features are reversible.

    Title The Effects of Carbohydrate Restriction in Patients with Diet-controlled Gestational Diabetes.
    Date April 1998
    Journal Obstetrics and Gynecology
    Excerpt

    OBJECTIVE: To determine the effect of carbohydrate restriction on perinatal outcome in patients with diet-controlled gestational diabetes mellitus (GDM). METHODS: Women with diet-controlled GDM were divided non-randomly into two groups based on their dietary carbohydrate content: those with low dietary carbohydrate content (below 42%) and those with high dietary carbohydrate content (exceeding 45%). Subjects kept dietary accounts and were followed with daily fasting and postprandial glucose assessments. Subjects also were tested daily for urinary ketones. Glycosylated hemoglobin, mean fasting and postprandial glucose values, incidence of macrosomia and large for gestational age (LGA) infants, cesarean deliveries for cephalopelvic disproportion and macrosomia, and need for insulin therapy were compared between the groups. RESULTS: The two groups were identical in terms of demographic characteristics. Significant reductions in the postprandial glucose values were seen among subjects in the low-carbohydrate group (P < .04). Fewer subjects in the low-carbohydrate group required the addition of insulin for glucose control (P < .047; relative risk [RR] 0.14; 95% confidence interval [CI] 0.02, 1.00). The incidence of LGA infants was significantly lower in the low-carbohydrate group (P < .035; RR 0.22; 95% CI 0.05, 0.91). Subjects in the low carbohydrate group also had a lower rate of cesarean deliveries for cephalopelvic disproportion and macrosomia (P < .037; RR 0.15; 95% CI 0.04, 0.94). CONCLUSION: Carbohydrate restriction in patients with diet-controlled GDM results in improved glycemic control, less need for insulin therapy, a decrease in the incidence LGA infants, and a decrease in cesarean deliveries for cephalopelvic disproportion and macrosomia.

    Title Cycles of Dose-intensive Chemotherapy with Peripheral Stem Cell Support in Persistent or Recurrent Platinum-sensitive Ovarian Cancer.
    Date February 1998
    Journal Gynecologic Oncology
    Excerpt

    OBJECTIVE: The objective was to determine the toxicity and surgically documented response rate of sequential high-dose chemotherapy with peripheral stem cell support in patients with persistent or recurrent cisplatin-sensitive ovarian cancer. METHODS: Fourteen patients (average age, 45 years) were treated with cyclophosphamide (4.5 g/m2), followed by granulocyte colony-stimulating factor (G-CSF)-stimulated peripheral stem cell harvests. The subsequent regimen prescribed three courses of carboplatin (1 g/m2) and cyclophosphamide (1.5 g/m2 with 2-mercaptoethanesulfonate) every 2 weeks with stem cell support. This was followed by three courses of paclitaxel at 250 mg/m2 every 2 weeks with G-CSF support only. Six patients were entered on the basis of a positive second-look laparotomy and 8 patients had a first recurrence after at least a 6-month disease-free interval. RESULTS: Fourteen patients were entered and 12 patients completed all planned courses of therapy (mean time, 13 weeks). Normal hematopoiesis was reestablished after each cycle. Hospitalization for neutropenic fever occurred in 11/93 cycles (11.8%). Thirteen patients required blood transfusions and in 12 patients platelet transfusions were given. One patient had grade 3 neurotoxicity. An initial elevated CA 125 returned to normal in 7/8 patients (88%) and 71% of patients with measurable disease responded to therapy. There were 2 pathologic complete responders (PCR), making the PCR rate 2/14 or 14% (0-35%). CONCLUSION: Although this regimen was well tolerated and clinical response rates were high, the surgically documented response rate was not clearly superior to conventional salvage regimens in platinum-sensitive patients.

    Title Predictive Factors for Neonatal Morbidity in Neonates with an Umbilical Arterial Cord Ph Less Than 7.00.
    Date December 1997
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    OBJECTIVE: Fewer than 50% of neonates with an umbilical arterial pH < 7.00 have neonatal complications. Our objective was to identify clinical predictive factors for adverse outcomes in this group of neonates. STUDY DESIGN: In this case-control study both cases and controls had an umbilical arterial cord pH < 7.00. Cases were defined as those neonates who had seizures, grade 3 to 4 intraventricular hemorrhage, gastrointestinal dysfunction, respiratory distress syndrome requiring intubation, sepsis, or death. Controls had an umbilical arterial cord pH < 7.00 and no complications. A multivariable prediction model was created, with variables having an association with adverse outcome by bivariate analyses, attempting to predict which neonates in this umbilical arterial pH range are at greatest risk for adverse outcomes. RESULTS: We identified 73 of 10,705 neonates born between July 1992 and October 1996 with an umbilical arterial cord pH < 7.00. Thirty-five neonates met our case definition, and the remaining 38 composed the control group. Cases had significantly lower arterial pH values and 1- and 5-minute Apgar scores, greater arterial base deficit values, and a higher incidence of abruptio placentae and maternal cocaine use. More cases were delivered before 34 weeks. There were three neonatal deaths, two cases of grade 3 or 4 intraventricular hemorrhage, five cases of gastrointestinal dysfunction, and four cases of neonatal seizures. In our predictive model for adverse neonatal outcome, an arterial base deficit > or = 16 mmol/L and a 5-minute Apgar score < 7 had a sensitivity and a specificity of 79% and 80.8%, respectively. CONCLUSION: Neonatal morbidity in neonates with an umbilical arterial cord pH < 7.00 can be predicted by a high arterial base deficit value and low 5-minute Apgar score.

    Title The Association Between Maternal Cocaine Use and Placenta Previa.
    Date December 1997
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    OBJECTIVE: Our aim was to determine whether maternal cocaine exposure is a risk factor for placenta previa. STUDY DESIGN: In this case-control study, cases of placenta previa confirmed at delivery (ascertained by International Classification of Diseases, ninth revision, Clinical Modification, code-based search, N = 40) were compared with a random sample of patients without placenta previa (N = 80) in a ratio of two controls per case. Data on antecedent maternal cocaine use, as well as other potential risk factors for placenta previa, were obtained from a review of the prenatal chart and the hospital record. Categorization of cocaine use was based on either patient self-report or urine toxicologic testing, or both. Multiple logistic regression was performed to assess the association between cocaine and placenta previa while we controlled for other variables. RESULTS: After the effects of other variables were adjusted for, maternal cocaine use was an independent risk factor for placenta previa (adjusted odds ratio = 4.39, 95% confidence interval 1.17 to 16.4). Other significant risk factors included a history of cesarean section and prior elective abortion. CONCLUSION: These results suggest that cocaine use, as well as prior cesarean section, prior elective abortion, and parity, are associated with placenta previa.

    Title Intrapartum Airway Management for Giant Fetal Neck Masses: the Exit (ex Utero Intrapartum Treatment) Procedure.
    Date December 1997
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    OBJECTIVE: Our goal was to review our experience with the EXIT (ex utero intrapartum treatment) procedure in the management of five cases with life-threatening fetal neck masses. STUDY DESIGN: We present a retrospective review of prenatal presentation and course, diagnostic accuracy of imaging studies, intraoperative management, complications, and outcomes. RESULTS: Polyhydramnios was the initial presenting symptom in three of five fetuses with a mean gestational age of 25 +/- 6 weeks. Preterm labor occurred in two patients. Fetal magnetic resonance imaging provided accurate diagnosis in all four cases whereas conventional ultrasonography led to the diagnosis in four of five cases. The mean duration of EXIT was 28 +/- 22 minutes. The mean venous cord blood gas values were pH 7.22 +/- 0.05, PCO2 61 +/- 11 mm Hg, and PO2 42 +/- 8 mm Hg. In four of five cases an airway was successfully secured. CONCLUSIONS: The EXIT procedure provides up to 1 hour of good uteroplacental support and is the procedure of choice to secure an airway in the fetus with a giant neck mass.

    Title Evidence for Magnesium Sulfate As a Tocolytic Agent.
    Date November 1997
    Journal Obstetrical & Gynecological Survey
    Excerpt

    The objective of our study is to quantitatively examine the available evidence regarding the efficacy and side effects of magnesium sulfate for acute tocolysis (from randomized trials) compared with placebo and beta-agonist agents. Randomized trials comparing magnesium sulfate with placebo or beta-agonists for tocolysis were identified with a MEDLINE-based search and was supplemented by a search of obstetrical textbooks and bibliographies. Trials underwent quality evaluation and data abstraction by two independent, blinded investigators. Outcomes evaluated included delivery delay of various durations as well as the frequency of major and minor side effects. Summary odds ratios and 95 percent confidence intervals for dichotomous outcomes were calculated using a random effects model. Interstudy heterogeneity for these outcomes was assessed with a Q statistic. We identified 12 randomized controlled trials of magnesium sulfate for acute tocolysis. Four studies were excluded because of either lack of comparison of magnesium sulfate to either placebo or beta-agonists or lack of reporting clinical outcomes of interest. The eight remaining randomized trials comparing magnesium sulfate with placebo or beta-agonists were included in this analysis. There was no significant difference between MgSO4 and placebo for any of the measured outcomes for delay in delivery. Comparing magnesium sulfate to ritodrine or beta-agonists did not demonstrate any differences between the agents in achieving clinically significant tocolysis. There was a significant difference between MgSO4 and beta-agonists in the frequency of medication discontinuation because of side effects, but not in the frequency of major adverse drug events. There are few data comparing magnesium sulfate with a placebo for acute tocolysis. Magnesium sulfate seems to be comparable to ritodrine and beta-agonists, although the available data are not sufficient for a rational choice between these agents.

    Title [observations on Pe-eclampsia-eclampsia and the Advances in the Evolution of Some Laboratory Tests].
    Date September 1997
    Journal Ginecología Y Obstetricia De México
    Excerpt

    The preeclampsia-eclampsia syndrome is a vasospastic disorder and probably has a placental origin. Once the hypertensive syndrome is established the uteroplacental blood flow is reduced as well as the intervillous blood flow. Since 18-24 weeks of gestation and before the symptoms of preeclampsia become overt, changes in placental flow velocity can be detected with Doppler technics. The placental theories for the etiology of preeclampsia are focused on the hypoxic effect in the trophoblastic tissue of second trimester. The placental ischemic changes are evident and seen in the uteroplacental bed. They are interrelated with the stages of trophoblastic invasion of the spiral arteries during the 14 and 20 weeks. When the trophoblastic invasion is over, the spiral arteries become a high resistance system. The defect observed in preeclampsia is the lack of invasion of the trophoblast to the maternal arteries. The diminished placental perfusion probably creates endothelial damage. This damage has several effects: decreased prostaglandin production, activated coagulation cascade, stimulated fibrin aggregation, and increased vascular permeability. The ideal laboratory test for preeclampsia shall predict the onset of this entity. Recent findings seem promising. The fibronectin concentration increases 2-3 wks. prior to the clinical manifestation of preeclampsia. Severe hypertension shows an abnormal decrease in fibronectin levels. Hypocalciuria has been described as an early predictor in the development of preeclampsia. Other agents undergoing extensive evaluation as predictors are: uric acid, b-thromboglobin, prolactin and atrial natriuretic peptide. Recently high levels of b-HCG (human corionic gonadotrophin) have been linked to a lack of trophoblastic invasion during the second trimester, therefore this is a potential marker for those patients that will eventually develop preeclampsia.

    Title Disseminated Congenital Neuroblastoma Involving the Placenta.
    Date August 1997
    Journal Archives of Pathology & Laboratory Medicine
    Excerpt

    Neuroblastoma, a tumor of primitive neuroectodermal cells, is one of the most common solid malignancies of neonates. Placental metastases have been described in rare cases of congenital neuroblastoma, usually in association with hydrops fetalis, placentomegaly, and widespread disease in the neonate. We report a case in which the unexpected diagnosis of neuroblastoma was made based on the postnatal finding of tumor emboli confined to fetal vessels of the placenta. Radiation and chemotherapy were given based on this diagnosis, obviating the need for an invasive diagnostic procedure.

    Title A Rapidly Growing Fetal Teratoma.
    Date June 1997
    Journal Lancet
    Title A Retrospective Analysis of Erb's Palsy Cases and Their Relation to Birth Weight and Trauma at Delivery.
    Date June 1997
    Journal The Journal of Maternal-fetal Medicine
    Excerpt

    Brachial plexus injury is assumed to be associated with the traumatic delivery of a macrosomic fetus in the vast majority of cases. This study was undertaken to examine the relationship of brachial plexus injury to birth weight and trauma at delivery, to compare our incidence to the incidence in other populations, and to examine how the incidence of brachial plexus injury has changed in our institution over the last 30 years. A retrospective analysis of 14,358 births from January 1, 1987, to June 30, 1991, identified 15 cases of brachial plexus injury (all Erb's palsy, incidence 0.10%). Maternal and neonatal charts were reviewed. There were 14 cases of Erb's palsy out of 11,484 vaginal deliveries (0.12%) and one case of Erb's palsy out of 2,874 cesarean deliveries. There was birth trauma (i.e., shoulder dystocia) noted at the time of delivery in eight cases (53.3%). However, a surprising finding was that in the other seven cases (46.7%) there was no evidence of shoulder dystocia at delivery. In the group in which Erb's palsy occurred and trauma was noted at the time of delivery, the average birth weight was 4,265 +/-480 g (range 3,550-5,110 g), with seven out of eight (88%) being large for gestational age (LGA). In the group in which Erb's palsy occurred but no trauma was noted at the time of delivery, the average birth weight was 2,906 +/- 745 g (range 1,590-3,950 g), with one out of seven (14%) being LGA. The infants without recognizable trauma weighed significantly less (P = 0.0009). In the group with trauma noted at delivery one out of eight (13%) received pitocin, and in the group without trauma noted at delivery one out of seven (14%) received pitocin. There was no significant difference in 5 min Apgar scores < 7 (3/8 vs. 0/7), umbilical cord pH (7.27 +/- 0.07 vs. 7.24 +/- 0.10), or base excess (-3.1 +/- 1.6 vs. -5.3 +/- 3.3) between those with recognizable trauma and those without recognizable trauma. The incidence of brachial plexus injury in this institution from 1987 to 1991 was 0.10%, which was unchanged from the incidence of 0.12% from 1954 to 1959, even though the cesarean rate rose from 5% to 20% during this period. The appearance of Erb's palsy in the newborn may not be as closely linked to birth weight and recognizable birth trauma as has previously been thought. In this study half the cases of Erb's palsy occurred in normal-sized infants without trauma noted at delivery. The incidence of Erb's palsy in our population is similar to that of other reported studies and has remained unchanged over the past 30 years, even as our cesarean rate has risen from 5% to 20%.

    Title The Risk of Periventricular-intraventricular Hemorrhage with Vacuum Extraction of Neonates Weighing 2000 Grams or Less.
    Date June 1997
    Journal Journal of Perinatology : Official Journal of the California Perinatal Association
    Excerpt

    OBJECTIVE: The objective of this retrospective study was to test the hypothesis that vacuum extraction of neonates with a birth weight < or = 2000 gm is associated with an increased risk of periventricular-intraventricular hemorrhage (PV-IVH). STUDY DESIGN: One hundred sixty-eight neonates weighing < or = 2000 gm were entered into this case control study. Fifty-six neonates delivered by silicone-rubber vacuum comprised the study group. For every infant born by vacuum-assisted delivery, two spontaneously delivered neonates served as controls (n = 112) and were matched for best obstetric gestational age (within 1 week), delivery date within 1 year, and birth weight < or = 2000 gm. Maternal and neonatal medical records were reviewed for demographic variables, antenatal complications, indication for vacuum-assisted delivery, neonatal birth weight, Apgar scores, umbilical cord blood gas values, and neonatal morbidity including the incidence of PV-IVH. All perinatal outcome variables were compared between the vacuum-assisted and spontaneously delivered groups. RESULTS: Both groups were similar with regard to maternal age, parity, antepartum complications, gestational age at delivery, neonatal birth weight, and gender. Both groups were also similar with regard to the incidence of 1-minute Apgar score < 5, small for gestational age, cephalhematoma, birth trauma, respiratory distress syndrome, hyperbilirubinemia, and sepsis. There was a significant increased incidence of 5-minute Apgar scores < 7 in the vacuum-assisted group (p = 0.04). No significant difference was observed in the incidence of PV-IVH grades 1 through 4 (21.4% vacuum group vs 16.1% control group, odds ratio 1.42, 0.58 to 3.45). CONCLUSION: Indicated use of the silicone-rubber vacuum to assist vaginal delivery of neonates weighing < or = 2000 gm does not appear to be associated with an increased risk of PV-IVH or other neonatal complications.

    Title Female Genital Mutilation. An Issue on the Doorstep of the American Medical Community.
    Date April 1997
    Journal The Journal of Legal Medicine
    Title Deletion Mapping of Two Potential Chromosome 14 Tumor Suppressor Gene Loci in Ovarian Carcinoma.
    Date February 1997
    Journal Cancer Research
    Excerpt

    Previous allelotyping studies of epithelial ovarian carcinoma suggest that loss of heterozygosity on chromosome 14q may be a common genetic alteration in this tumor type. The purpose of this study was to determine a precise frequency of chromosome 14q allelic loss in ovarian carcinomas and to define a minimal region(s) of deletion. Seventy-six ovarian carcinomas representative of the complete spectrum of grade, stage, and histological subtype were selected for PCR-based deletion mapping analysis using 15 highly polymorphic microsatellite markers spanning the length of this chromosome arm. Loss of heterozygosity was observed in 49% of the tumors studied, placing 14q among the most frequently affected chromosomal regions in ovarian cancer. Deletions were observed in all tumor grades and stages and in all histological subtypes except tumors of low malignant potential. Deletion of the entire chromosome arm was rare; the majority of tumors displayed partial losses, providing an informative basis for detailed deletion mapping. Two distinct minimal regions of deletion were delineated. One region was defined by markers D14S80 and D14S75 at 14q12-13, and the other region was defined by markers D14S65 and D14S267 at 14q32. These data implicate the involvement of two tumor suppressor genes on chromosome 14q in a substantial fraction of ovarian carcinomas.

    Title Effect of Surgical Debulking on Survival in Stage Iv Ovarian Cancer.
    Date February 1997
    Journal Gynecologic Oncology
    Excerpt

    In order to determine whether optimal surgical debulking in Stage IV epithelial ovarian cancer impacts survival, a retrospective review of patients treated at the University of Pennsylvania Cancer Center (UPCC) from 1984 to 1995 diagnosed with Stage IV epithelial ovarian cancer was performed. Data were collected regarding grade, histology, reason for allocation to Stage IV, extent of surgery performed and residual disease at initial staging procedure, major perioperative complications, first-line chemotherapy regimen, length of inpatient hospital stay, outcome at second-look laparotomy, follow-up, and survival. For the purposes of this study, optimal cytoreduction was defined as a residual disease of 2 cm or less. Forty-seven patients with Stage IV epithelial ovarian cancer identified in the Society of Gynecologic Oncologists (SGO) Database at UPCC are included. Fourteen of 47 (30%) were optimally cytoreduced at the time of their staging procedure. Twenty-six of 47 (55%) were deemed Stage IV by virtue of positive pleural effusion cytology only. Twenty-one of 47 (45%) had intraparenchymal liver involvement or metastatic disease outside of the abdomen. The median survival of the suboptimally debulked group was 17 months, while median survival in the optimal group was 37 months (P = 0.0295). These data suggest that Stage IV epithelial ovarian cancer patients with less than 2 cm residual disease have a survival advantage over patients with greater than 2 cm residual.

    Title Advanced Maternal Age: Perinatal Outcome when Controlling for Physician Selection.
    Date January 1997
    Journal Journal of Perinatology : Official Journal of the California Perinatal Association
    Excerpt

    OBJECTIVE: Our purpose was to determine whether differences in maternal outcome because of maternal age could be controlled by the elimination of bias in physician selection. STUDY DESIGN: We performed a case-control study that compared pregnancy outcomes of 164 patients delivered at our institution at > or = 40 years old with outcomes in a control group consisting of the next two deliveries by the same attending physician of women with ages 20 to 29 years. Retrospective analysis of the antepartum and intrapartum records was done to compare clinical outcome. RESULTS: We observed a significant increased incidence of nulliparous cesarean delivery (p = 0.046), elevated results of glucose screens with a 50 gm load (p = 0.00002), and hypertension throughout pregnancy in the older patients in spite of controlling for physician selection. The older patient group was more likely to have used assisted reproductive techniques (p = 0.000005) and had higher baseline weights (p = 0.001) and maximum pregnancy weights (p = 0.042). However, the neonatal outcome was similar in both groups. Despite controlling for physician selection, we demonstrated increased rates of abdominal delivery, glucose intolerance, and hypertension in older patients. Fetal and neonatal outcomes were similar in both groups. CONCLUSION: Women > or = 40 years old tend to have an increased incidence of a few pregnancy-related complications, even when controlling for physician selection.

    Title Racial Differences in Survival from Gynecologic Cancer.
    Date December 1996
    Journal Obstetrics and Gynecology
    Excerpt

    OBJECTIVE: To determine whether survival from gynecologic cancer is different between African-American and white patients at an inner-city hospital with both a large clinic and a private service. METHODS: We studied 538 patients (89 African American, 449 white) diagnosed with cervical, uterine, or ovarian cancer at a single institution from January 1, 1989 through December 31, 1993. Information was obtained on age, stage, site of disease, histology, and type of health insurance (public or commercial). Insurance coverage was used as a proxy for socioeconomic status. Overall survival was estimated by the method of Kaplan and Meier and compared by the log-rank test. Cox proportional hazard modeling was used to evaluate the effects of multiple factors on survival. RESULTS: African-American patients were significantly older and were more likely to have cervical cancer and public insurance than white patients. Overall survival was worse for African-American patients than for white patients (P < .05). However, stage for stage, there was no significant difference in survival between the groups. There was also no difference when patients were grouped by insurance status. African Americans had a significantly worse survival for cervical cancer than whites, and African-American patients older than 65 years had a worse survival than whites of similar age. On multivariate analysis, only stage and insurance coverage were significant predictors of survival. CONCLUSIONS: African-American patients with gynecologic cancer at our institution have worse overall survival than white patients. The survival difference seems to be due predominantly to differences in socioeconomic status and stage at diagnosis.

    Title Does Station of the Fetal Head at Epidural Placement Affect the Position of the Fetal Vertex at Delivery?
    Date December 1996
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    The objective study was to determine whether epidural placement before engagement of the fetal head is associated with an increase in the incidence of malposition at delivery.

    Title Reduction of Right Atrial Peak Systolic Velocity in Growth-restricted Discordant Twins.
    Date December 1996
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    The objective of this study was to measure blood flow velocity changes through the tricuspid valve in intrauterine growth-restricted twins.

    Title Clinical and Pathological Features of Ovarian Cancer in Women with Germ-line Mutations of Brca1.
    Date November 1996
    Journal The New England Journal of Medicine
    Excerpt

    BACKGROUND: We tested the hypothesis that ovarian cancers associated with germ-line mutations of BRCA1 have distinct clinical and pathological features as compared with sporadic ovarian cancers. METHODS: We reviewed clinical and pathological data on patients with primary epithelial ovarian cancer found to have germ-line mutations of BRCA1. Survival among patients with advanced-stage cancer and such mutations was compared with that in control patients matched stage, grade, and histologic subtype of the tumors. A combination of single-strand conformation and sequencing analyses was used to examine the 22 coding exons and intronic splice-donor and splice-acceptor regions of BRCA1 for mutations in pathological specimens. Alternatively, some patients were known to be obligate carriers of the mutant BRCA1 gene because of their parental relationships with documented mutant-gene carriers. RESULTS: We identified 53 patients with germ-line mutations of BRCA1. The average age at diagnosis was 48 years (range, 28 to 78). Histologic examination in 43 of the 53 patients showed serous adenocarcinoma. Thirty-seven tumors were of grade 3, 11 were of grade 2, 2 were of grade 1, and 3 were of low malignant potential. In 38 patients, the tumors were of stage III; 9 patients (including those with tumors of low malignant potential) had stage I disease, 5 had stage IV, and 1 had stage II. As of June 1996, with a median follow-up among survivors of 71 months from diagnosis, 20 patients had died of ovarian cancer, 27 had no evidence of the disease, 4 were alive with the disease, and 2 had died of other diseases. Actuarial median survival for the 43 patients with and advanced-stage disease was 77 months, as compared with 29 months for the matched controls (P<0.001). CONCLUSIONS: As compared with sporadic ovarian cancers, cancers associated with BRCA1 mutation appear to have a significantly more favorable clinical course.

    Title Cervical Assessment: Visual or Digital?
    Date November 1996
    Journal Journal of Perinatology : Official Journal of the California Perinatal Association
    Excerpt

    Our hypothesis for this study was that visual cervical assessment is not equivalent to digital assessment in patients with uterine contractions. We compared visual with digital cervical examinations done on 133 gravid women evaluated in the labor and delivery department because of uterine contractions. Patients at 27 weeks' gestation or more, subjectively in early labor, were prospectively entered into the study. Cervical dilatation and effacement were determined by two separate examiners blinded to each other's assessment, one by digital examination and the other by visual examination, in random order no more than 5 minutes apart. Eight of 133 patients were excluded from data analysis because of inability to visualize the cervix during speculum examination. Data analysis was done with correlation coefficient and the Bland and Altman test for agreement of two clinical measurements. Visual examination only underestimated actual cervical dilation by 0.60 cm (95% confidence interval [CI] 0.58 to 0.62 cm) and the limits of agreement were -2.06 cm (95% CI -2.02 to -2.09 cm) to 3.25 cm (95% CI 3.21 to 3.29 cm). Similarly, visual assessment underestimated effacement by 14.2% (95% CI 13.7% to 14.6%) and the limits of agreement were -41.3% (95% CI -40.5% to 42.0%) to 69.9% (95% CI 68.8% to 70.4%). In conclusion, cervical assessment in patients with uterine contractions who are thought to be in labor by visual speculum examination is not equivalent to that by digital examination. This difference seems to only be clinically significant if the cervix is more than 3 cm dilated.

    Title Prevention of Rh Isoimmunization After Spontaneous, Massive Fetomaternal Hemorrhage.
    Date October 1996
    Journal Southern Medical Journal
    Excerpt

    Massive fetomaternal hemorrhage has been associated with numerous risk factors and can occur spontaneously. The risk is probably greater when a woman who is Rh negative has an ABO-compatible fetus. We report the case of a gravid, A-negative unsensitized patient who came to the hospital at term complaining of decreased fetal movement over the previous 24 hours. During evaluation, the fetal heart rate was found to have decreased beat-to-beat variability and repetitive late decelerations, and the mother was delivered of a 3,005 gA-positive neonate (by cesarean section) with a hemoglobin level of 2.9 g/dL. An acid elution test showed 400 mL of fetal blood in the maternal circulation, and the patient received 23 ampules (6,900 micrograms) of Rh immune globulin postpartum. The patient's condition was observed for 156 days after delivery; she did not become sensitized to the Rh factor. A massive fetomaternal hemorrhage can occur without any antecedent risk factors, with a risk of subsequent morbidity to the neonate. Sensitization can be prevented by prompt administration of adequate amounts of Rh immune globulin.

    Title Transforming Nursing's Vision: History, Holism, and the Health Care System.
    Date September 1996
    Journal Kentucky Nurse
    Title Mutations of the Brca2 Gene in Ovarian Carcinomas.
    Date August 1996
    Journal Cancer Research
    Excerpt

    Inherited mutations in the recently discovered BRCA2 gene are believed to be responsible for a significant fraction of early-onset hereditary breast cancers. Unlike BRCA1, however, which confers a high risk to both breast and ovarian cancer, the incidence of ovarian cancer appears to be much lower In BRCA2-linked families, causing uncertainty as to the relevance of BRCA2 to hereditary ovarian cancer. Numerous allelotype studies indicate that allelic deletions Including the BRCA2 locus on chromosome 13q are common in ovarian cancers in general, suggesting that somatic mutations of this gene may be involved in sporadic ovarian tumorigenesis. The purpose of this study was to test the hypothesis that germline or somatic mutations of BRCA2 are associated with hereditary and/or sporadic ovarian cancers, respectively. The entire 10.2-kb coding region of BRCA2 was screened for mutations in 130 consecutive ovarian tumors, the only selection criterion being a pathological diagnosis of epithelial ovarian carcinoma. Loss of heterozygosity at markers flanking BRCA2 was observed in 56% of the tumors. Four germline mutations and two somatic mutations were identified; two of the germline mutations are recurrent, having been previously described. Remarkably, the patients with germline mutations were late-onset cases with no medical or family histories suggestive of hereditary cancer. These data suggest that mutations of BRCA2 are rare in sporadic ovarian cancers, and that the proportion of ovarian cancers resulting from hereditary predisposition may be higher than previously suspected based on estimates derived from studies of highly penetrant genetic loci.

    Title Dating of Pregnancy by Trimesters: a Review and Reappraisal.
    Date July 1996
    Journal Obstetrical & Gynecological Survey
    Excerpt

    Many patients and obstetricians divide the events of human pregnancy into three intervals traditionally termed "trimesters." This system presumably arose from an equal division of the "9 months of pregnancy" into 3-month intervals. There are several problems with this system that follows pregnancy by months or trimesters. First, the average human pregnancy lasting 280 days or 40 weeks is not evenly divisible by three, leaving one to wonder how long each trimester is. Second, conversion from "weeks pregnant" to "months pregnant" is often an estimate that can foster misunderstanding between the patient and her obstetrician. Last, following pregnancy by the Gregorian calendar does not reflect embryonic or fetal developmental milestones. We propose a revision of this system to one in which natural embryonic and fetal developmental landmarks are used instead of trimesters to define the progressive stages of pregnancy. These landmarks occur approximately at 5-week intervals allowing a more simple division of pregnancy into four 10-week quartiles, each with two 5-week intervals. This article reviews many of these important landmarks within this framework. This system emphasizes a developmentally based way of understanding the events of pregnancy for both the patient and the obstetrician.

    Title Cocaine's Effect on Plasma Oxytocin Concentrations in the Baboon During Late Pregnancy.
    Date July 1996
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    The hypothesis for this investigation was that intravenous cocaine would result in an elevation of maternal plasma oxytocin levels in the baboon during late pregnancy.

    Title Naturally Occurring Insulin Autoantibodies in Neonates of Normal Pregnancies and Their Relationship to Insulinemia and Birth Weight.
    Date May 1996
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    OBJECTIVE: The objectives of this study were to determine whether insulin autoantibodies are present in umbilical cord blood from normal pregnancies, determine whether cord blood insulin autoantibody levels correlate with respective maternal levels at delivery, determine whether cord blood insulin autoantibody levels are related to cord blood or maternal insulin levels, and to determine what relationship neonatal birth weight has with either cord blood insulin autoantibody and insulin levels or maternal insulin autoantibody and insulin levels. STUDY DESIGN: Paired umbilical cord and maternal serum samples were taken from 70 normal subjects at delivery. Measurements of serum insulin autoantibody (competitive charcoal radiobinding assay) and insulin (radioimmune inhibition assay) levels were performed. Multiple linear regression analysis and paired t tests were used for data analyses. RESULTS: Neonatal insulin autoantibody levels (120 nU/ml) were more than two times higher than maternal levels (49 nU/ml) (p < 0.001). No correlation was observed between neonatal and maternal insulin autoantibody levels (r = 0.14, p = 0.25). A positive correlation of both neonatal and maternal insulin with birth weight was observed (r = 0.28, p < 0.02; and r = 0.36, p < 0.01, respectively). CONCLUSIONS: These results suggest that the insulin autoantibody levels in fetal cord blood are not related to maternal levels in normal uncomplicated pregnancies. In addition, insulin levels in both maternal and neonatal circulations were positively correlated with increased birth weight in the normal pregnancies studied.

    Title Decreasing the Cesarean Section Rate in a Private Hospital: Success Without Mandated Clinical Changes.
    Date March 1996
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    OBJECTIVE: We analyzed the delivery statistics from our institution to describe a successful program of cesarean section delivery reduction and to help us understand what factors explained the reduction. STUDY DESIGN: A retrospective analysis of various cesarean section rates and risk factors from a prospectively collected delivery database of all patients delivered between May 15, 1988, and June 30, 1994. During the study period we instituted a program of increasing awareness, confidential provider feedback, more aggressive laboring techniques, and other clinical guidelines. The delivery data were divided into 6-month intervals and analyzed by chi 2 tables. RESULTS: The overall cesarean section rate fell from 31.1% to 15.4%. Similar reductions were noted in the primary (17.9% to 9.8%) and repeat cesarean section rates (13.2% to 5.7%). The primary cesarean section rate fall was accompanied by a drop in abdominal delivery for cephalopelvic disproportion and fetal distress. The repeat cesarean section rate is explained by a significant increase in trial and successful vaginal birth after cesarean delivery. No increase in maternal, fetal, or neonatal morbidity or mortality was observed. CONCLUSIONS: We have demonstrated that the cesarean delivery rate can be safely lowered in a private hospital without mandated clinical changes. Our data suggest that careful and detailed feedback can lead to improved clinical practice.

    Title Differential Contribution of Dorsal and Ventral Medial Prefrontal Cortex to the Acquisition and Extinction of Conditioned Fear in Rats.
    Date December 1995
    Journal Behavioral Neuroscience
    Excerpt

    The emotional reactivity of rats with lesions of the dorsal portion of medial prefrontal cortex (mPFC) was examined using a classical fear conditioning paradigm. Conditioned fear behavior (freezing responses) was measured during both the acquisition and extinction phases of the task. Lesions enhanced fear reactivity to both the conditioned stimulus (CS) and contextual stimuli during both phases, suggesting that dorsal mPFC lesions produce a general increase in fear reactivity in response to fear conditioning. M. A. Morgan, L. M. Romanski, and J. E. LeDoux (1993) found that lesions just ventral to the present lesions had no effect during acquisition of the same task and prolonged the fear response to the CS (but not the context) during extinction. Thus, both dorsal and ventral regions of mPFC are involved in the fear system, but each modulates different aspects of fear responsivity.

    Title Phosphoryl Migration During the Chemical Synthesis of Rna.
    Date November 1995
    Journal Nucleic Acids Research
    Excerpt

    By the use of high sensitivity assay systems, we have measured the occurrence of strand scission and phosphoryl migration that accompany the deblocking of chemically synthesized oligoribonucleotides. Substantial phosphoryl migration was observed for both enzymatically derived poly(uridylic acid) and synthetic uridine oligoribonucleotides 2'-O-protected with the 1-(2-fluorophenyl)-4-methoxypiperidin-4-yl (Fpmp) group, when these species were subjected to the acidic conditions suggested for Fpmp deprotection. Strand scission occurred in parallel and could be demonstrated readily by 5'-32P end labeling, but not by 3'-32P end labeling, of the acid-treated oligoribonucleotides. Increasing the pH of the deprotection solution and decreasing the temperature at which the deprotection was accomplished diminished both phosphoryl migration and strand scission. A mechanism that can rationalize these results is discussed.

    Title Postprandial Versus Preprandial Blood Glucose Monitoring in Women with Gestational Diabetes Mellitus Requiring Insulin Therapy.
    Date November 1995
    Journal The New England Journal of Medicine
    Excerpt

    BACKGROUND. The fetuses of women with gestational diabetes mellitus are at risk for macrosomia and its attendant complications. The best method of achieving euglycemia in these women and reducing morbidity in their infants is not known. We compared the efficacy of postprandial and preprandial monitoring in achieving glycemic control in women with gestational diabetes. METHODS. We studied 66 women with gestational diabetes mellitus who required insulin therapy at 30 weeks of gestation or earlier. The women were randomly assigned to have their diabetes managed according to the results of preprandial monitoring or postprandial monitoring (one hour after meals) of blood glucose concentrations. Both groups were also monitored with fasting blood glucose measurements. The goal of insulin therapy was a preprandial value of 60 to 105 mg per deciliter (3.3 to 5.9 mmol per liter) or a postprandial value of less than 140 mg per deciliter (7.8 mmol per liter). Obstetrical data and information on neonatal outcomes were collected. RESULTS. The prepregnancy weight, weight gain during pregnancy, gestational age at the diagnosis of diabetes and at delivery, degree of compliance with therapy, and degree of achievement of target blood glucose concentrations were similar in the two groups. The mean (+/- SD) change in the glycosylated hemoglobin value was greater in the group in which postprandial measurements were used (-3.0 +/- 2.2 percent vs. 0.6 +/- 1.6 percent, P < 0.001) and the infants' birth weight was lower (3469 +/- 668 vs. 3848 +/- 434 g, P = 0.01). Similarly, the infants born to the women in the postprandial-monitoring group had a lower rate of neonatal hypoglycemia (3 percent vs. 21 percent, P = 0.05), were less often large for gestational age (12 percent vs. 42 percent, P = 0.01) and were less often delivered by cesarean section because of cephalopelvic disproportion (12 percent vs. 36 percent, P = 0.04) than those in the preprandial-monitoring group. CONCLUSIONS. Adjustment of insulin therapy in women with gestational diabetes according to the results of postprandial, rather than preprandial, blood glucose values improves glycemic control and decreases the risk of neonatal hypoglycemia, macrosomia, and cesarean delivery.

    Title Labor and Delivery Management of the Multiple Gestation.
    Date September 1995
    Journal Obstetrics and Gynecology Clinics of North America
    Excerpt

    Labor and delivery management of multiple gestations remains controversial. The authors review issues relating to the management of labor and the administration of anesthesia in twin gestations. A comprehensive review of published data pertaining to delivery route planning for twins using fetal presentation, gestational age, and estimated fetal weight is presented. Individualization of intrapartum care in twin gestations is imperative.

    Title The Impact of Amniotic Fluid Volume Assessed Intrapartum on Perinatal Outcome.
    Date September 1995
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    Our purpose was to determine the value of routine intrapartum amniotic fluid volume assessment on perinatal outcome.

    Title Recurrent Squamous Cell Carcinoma of the Cervix with Pulmonary Lymphangitic Metastasis.
    Date May 1995
    Journal International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics
    Excerpt

    A case report and review of the world literature are presented to examine all the reported cases of cervical carcinoma manifesting as pulmonary lymphangitic carcinomatosis in order to better understand this rare condition. The clinical and pathologic features of this disease process are reviewed, as are potential treatment options. We present the first reported case of an immunocompromised patient with cervical carcinoma and pulmonary lymphangitic metastasis with a prospective diagnosis made by transbronchial biopsy. Given that this condition carries a uniformly fatal prognosis, unwanted therapy may result from a missed diagnosis. A prospective pathologic diagnosis by transbronchial biopsy may guide appropriate therapy in these patients.

    Title Secondary Cytoreduction in Epithelial Ovarian Cancer.
    Date April 1995
    Journal Critical Reviews in Oncology/hematology
    Title Intrapartum Electronic Fetal Heart Rate Monitoring Versus Intermittent Auscultation: a Meta-analysis.
    Date April 1995
    Journal Obstetrics and Gynecology
    Title Antepartum Surveillance for a History of Stillbirth: when to Begin?
    Date March 1995
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    OBJECTIVE: A history of stillbirth is universally accepted as an indication for antepartum fetal heart rate testing. Our goal was to examine when fetal testing should begin in an otherwise healthy patient with a history of stillbirth. STUDY DESIGN: This is a nonconcurrent cohort study of patients who were seen for antepartum surveillance from January 1979 to December 1991 with a history of stillbirth as the only indication for testing. Subsequent pregnancies were evaluated for adverse outcomes and abnormal antepartum test results. RESULTS: There was one case of recurrent stillbirth among the 300 study patients. Nineteen patients (6.4%) had one or more positive antepartum surveillance tests (positive contraction stress test or biophysical profile < or = 4). Three patients (1%) had positive tests before 32 weeks, all of whom were subsequently delivered without incident at term. Three patients were delivered for positive tests at < 36 weeks, one by cesarean section for fetal distress. We could not detect a relationship between the gestational age of the previous stillborn and the incidence of abnormal tests or fetal distress in subsequent pregnancies. CONCLUSION: Antepartum surveillance should begin at > or = 32 weeks in the healthy pregnant woman with a history of stillbirth.

    Title Preterm Premature Rupture of Membranes and Abruptio Placentae: is There an Association Between These Pregnancy Complications?
    Date March 1995
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    OBJECTIVE: Our purpose was to determine whether the incidence of abruptio placentae is increased in pregnancies with preterm premature rupture of membranes and to assess whether certain clinical risk factors in this group predispose them to have abruptio placentae. STUDY DESIGN: A retrospective cohort study over a 2.5-year period was performed. The study group consisted of 756 singleton pregnancies between 20 and 36 weeks' gestation complicated by preterm premature rupture of membranes and managed expectantly. The control group consisted of 11,240 pregnancies not complicated by preterm premature rupture of membranes and delivered during the same time period. The incidence of abruptio placentae was compared between the two groups. The study group of patients with preterm premature rupture of membranes was further subdivided into cases with (n = 38) and without abruptio placentae (n = 718) and compared. Clinical factors such as admission amniotic fluid index, history of bleeding before or after rupture of membranes, incidence of intrapartum fetal distress, and low 5-minute Apgar scores (< 6), latency-to-delivery interval, gestational age and weight at delivery, and incidence of amnionitis and endometritis were compared. RESULTS: The incidence of abruptio placentae in the study group (38/756, 5%) was significantly higher than that in the control group (97/11, 240, 0.9%) (p < 0.001, odds ratio = confidence interval). Comparison of cases with preterm premature rupture of membranes with and without abruptio placentae demonstrated both groups to have a similar gestational age at delivery, birth weight, latency-to-delivery interval, amniotic fluid index, and infectious morbidity. The group with abruptio placentae had a significantly higher incidence of bleeding before rupture of membranes (six of 38, 15% vs eight of 718, 1%; p < 0.005) and of intrapartum fetal distress (18/38, 46% vs 49/718, 7%; p < 0.0009). CONCLUSIONS: Pregnancies complicated by preterm premature rupture of membranes that are managed expectantly are at significant risk for abruptio placentae. Preterm premature rupture of membranes in such cases is more often preceded by bleeding. These abruptions may predispose the patient to intrapartum fetal distress.

    Title The "dangerous Multipara": Fact or Fiction?
    Date March 1995
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    OBJECTIVE: Our purpose was to compare the intrapartum complication incidence among grand multiparous women with that of age-matched control multiparous women. STUDY DESIGN: A total of 382 grand multiparous women (para > or = 5) were compared with 382 age-matched control subjects (para 2 to 4), all delivering between July 1989 and September 1991. Intrapartum complications classically associated with grand multiparity (abruptio placentae, dysfunctional labor, fetal malpresentation, postpartum hemorrhage, and shoulder dystocia) were compared. RESULT: Both groups had comparable antepartum complications and gestational ages at delivery. The overall intrapartum complication incidence for grand multiparous women was 33% (127/382 patients), not significantly different from that of the control multiparous women, 27% (103/382). Grand multiparity was associated with an increased incidence of macrosomia (16% vs 11%) and a decreased incidence of operative delivery (14% vs 21%). Macrosomia increased the incidence of intrapartum complications from 31% to 46% (p < 0.03) in the grand multiparous patients, and a trend was observed in the multiparous patients, from 26% to 37%. However, when properly controlled, this was noted to be a confounding variable and was not related to parity. CONCLUSIONS: In a largely Hispanic population grand multiparous patients do not have an increased incidence of intrapartum complications.

    Title Term Early-onset Neonatal Seizures: Obstetric Characteristics, Etiologic Classifications, and Perinatal Care.
    Date February 1995
    Journal Obstetrics and Gynecology
    Excerpt

    OBJECTIVE: To describe obstetric characteristics and etiologic classifications and assess perinatal care in term neonates with early-onset seizures. METHODS: We performed a retrospective review of neonatal and obstetric records of neonates delivered at term with a diagnosis of early-onset seizures between January 1981 and December 1992 at Long Beach Memorial Medical Center. Data regarding obstetric characteristics and etiologic classifications of the seizures were abstracted from the medical records. Lack of antepartum testing in high-risk patients, delayed intervention with nonreassuring antepartum or intrapartum fetal heart rate patterns, birth trauma, and failure to use prophylactic antibiotics or treat infection were the criteria used for identifying seizures that were potentially preventable. RESULTS: Forty term neonates had early-onset seizures out of 60,712 live births (0.07%). These seizures were attributed to hypoxic events in 15 neonates (37.5%), cerebral malformations in seven (17.5%), cerebral infarcts in seven (17.5%), intracranial hemorrhage in five (12.5%), infection in three, and an unknown etiology in three. Twenty-three neonates had 5-minute Apgar scores of 7 or greater (cerebral malformations excluded). Seven of these neonates (30%) had cerebral infarcts. A review of all records identified nine cases (22.5%) of the early-onset seizures as potentially preventable. CONCLUSION: The majority of the term early-onset neonatal seizures identified did not appear to be preventable. Many of the neonates with 5-minute Apgar scores of 7 or greater had cerebral infarcts.

    Title Efficacy of Intraperitoneal Sodium Carboxymethylcellulose in Preventing Postoperative Adhesion Formation.
    Date January 1995
    Journal The Journal of Reproductive Medicine
    Excerpt

    Various regimens to reduce postoperative intraperitoneal adhesion formation have been tested; however, none has been consistently successful. The purpose of this study was to compare the efficacy of three compounds instilled into the peritoneal cavity--32% dextran 70, 0.9% normal saline and sodium carboxymethylcellulose--to no therapy on their ability to prevent postoperative adhesion formation in the New Zealand white rabbit. Bilateral posterior uterine horn incisions and cecal and transverse colon abrasions were performed during a two-phased study on each of 25 rabbits that were randomly assigned in a blind fashion into one of four study groups. Two weeks postoperatively, each rabbit underwent an autopsy to assess the magnitude of intraperitoneal adhesion formation. Adhesion scores were determined by counting the number of adhesions and assigning one or two points for each thin, filmy or dense, broad adhesion. As compared to no therapy, all three substances tested significantly reduced adhesion formation. Although 32% dextran 70 and 0.9% normal saline showed similar results, the degree of adhesion formation was reduced most significantly with sodium carboxymethylcellulose (P < .002) Sodium carboxymethylcellulose is effective in preventing postoperative adhesion formation in the New Zealand white rabbit.

    Title Type I Fetal Cystic Adenomatoid Malformation of the Lung with Hydrops at 18 Weeks' Gestation: a Case Report.
    Date December 1994
    Journal Journal of Perinatology : Official Journal of the California Perinatal Association
    Excerpt

    Fetal cystic adenomatoid malformation, type I, is a rare pulmonary anomaly that has been diagnosed after 20 weeks' gestation. The prognosis of this malformation is usually dependent on whether it is microcystic, types II and III, or macrocystic, type I. We report a case of severe macrocystic fetal cystic adenomatoid malformation diagnosed at 18.4 weeks' gestation. This case demonstrates that fetal cystic adenomatoid malformation can be diagnosed at 18 weeks and that hydrops with oligohydramnios may be part of the natural history of type I lesions this early in pregnancy.

    Title Gestational Diabetes: Does the Presence of Risk Factors Influence Perinatal Outcome?
    Date November 1994
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    OBJECTIVE: Our purpose was to determine whether gestational diabetics with risk factors for gestational diabetes have worse glucose tolerance and poorer birth outcomes than those without risk factors. STUDY DESIGN: We conducted a nonconcurrent cohort study of gestational diabetics identified by universal screening and delivered from Jan. 1, 1990, to Dec. 31, 1992. Multiple gestations and patients with chronic medical conditions were excluded. The following risk factors for gestational diabetes mellitus were abstracted: obesity (> 80 kg), family history of diabetes, previous gestational diabetes mellitus, and previous macrosomic, stillborn, or anomalous fetus. Patients with one or more risk factors were compared with those without risk factors. A group of low-risk nondiabetic patients served as controls. The incidences of A2 diabetes mellitus, cesarean section, neonatal macrosomia, and shoulder dystocia were the outcome variables of interest. RESULTS: Selective screening would have failed to detect 43% of gestational diabetics. Twenty-eight percent of the missed gestational diabetics would have required insulin (class A2). When compared with controls, patients with gestational diabetes mellitus were at increased risk for macrosomia (26% vs 11%, p < 0.01), cesarean section (37% vs 15%, p < 0.01), and shoulder dystocia (9% vs 2%, p < 0.05). Patients with and without risk factors did not differ in mean maternal age, gestational age at delivery, birth weight, incidence of requiring insulin, macrosomia, or cesarean delivery. The similarities between those with and without risk factors remained after stratification by maternal age (> or = 30 years). CONCLUSION: Gestational diabetics are at increased risk for adverse birth outcomes compared with low-risk controls. Class A2 diabetes mellitus and fetal macrosomia with its attendant risks are equally prevalent among patients with and without risk factors for gestational diabetes mellitus. Because > 40% of cases will be missed with selective screening, universal screening should be favored for detection of gestational diabetes mellitus.

    Title Iron(ii) Bleomycin-mediated Degradation of a Dna-rna Heteroduplex.
    Date September 1994
    Journal Biochemistry
    Excerpt

    The effect of iron(II) bleomycin on a DNA-RNA heteroduplex was investigated using a substrate formed by reverse transcription of Escherichia coli 5S ribosomal RNA. Both strands of the heteroduplex were cleaved by FeII.BLM A2 at comparable concentrations; complete digestion of both strands was observed using 5 microM FeII.BLM A2. The DNA strand of the heteroduplex was cleaved predominantly at 5'-G-pyr-3' sites; the sites of cleavage of the DNA strand were a subset of those observed for the corresponding DNA strand of a DNA duplex of identical sequence. The sites of cleavage of the RNA strand of the heteroduplex involved both purines and pyrimidines and were found to be different than the sites of cleavage of the 5S rRNA alone, demonstrating that cleavage of the former must actually have involved heteroduplex recognition by FeII.BLM A2. Both the DNA and RNA strands of the heteroduplex were cleaved by FeII.BLM A2 in the presence of physiological concentrations of Mg2+, consistent with the possibility that DNA-RNA heteroduplexes may be therapeutically relevant targets for bleomycin.

    Title Pneumonia in the Neonatal Intensive Care Unit. Diagnosis by Quantitative Bacterial Tracheal Aspirate Cultures.
    Date September 1994
    Journal Journal of Perinatology : Official Journal of the California Perinatal Association
    Excerpt

    Growth of > or = 10(5) colonies of bacteria per milliliter obtained at bronchoscopy in children and adults correlates with bacterial pneumonia. To determine whether quantitative tracheal aspirate cultures aid in diagnosis of pneumonia in the neonatal intensive care unit setting, tracheal aspirates were obtained from 25 infants who had recently undergone endotracheal intubation; 15 of the infants had suspected pneumonia and 10 control infants had undergone intubation for suspected apnea of prematurity (4 infants) or elective surgery (6 infants). Studies also were performed to detect Mycoplasma, Ureaplasma, viruses, and Pneumocystis. Tracheal aspirates from 2 of 15 infants with suspected pneumonia grew > or = 10(5) bacteria, and 1 was positive for respiratory syncytial virus. These infants were considered to have pneumonia. In 12 infants whose tracheal aspirates grew < 10(5) bacteria, respiratory decompensation later was explained by other causes in 11 infants, and there was one false-negative culture. There were three false-positive tracheal aspirates in the control group. We conclude that tracheal aspirates of infants who have recently had an endotracheal tube placed may be useful for diagnosing pneumonia and for identifying the causative agent.

    Title Endometriosis and Tamoxifen Therapy.
    Date August 1994
    Journal International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics
    Excerpt

    Tamoxifen is an estrogen antagonist/agonist often associated with antiestrogenic effects such as hot flushes and vaginal dryness in premenopausal women. Estrogenic side-effects, such as thromboembolic phenomena and endometrial proliferation has been reported in postmenopausal women. Paradoxically, tamoxifen has also been shown to be capable of increasing estrogen levels in premenopausal women. Since tamoxifen is being used more frequently in this group of women, potential adverse effects are only now being recognized. Two cases of premenopausal women who developed symptomatic endometriomas while on tamoxifen for breast cancer, are reported. Stimulation of endometriosis should be considered when pain and an ovarian mass develops in a woman on tamoxifen. The unique effects of tamoxifen in premenopausal women may contribute to this even in the presence of regular ovulation.

    Title Abruptio Placentae: Perinatal Outcome in Normotensive and Hypertensive Patients.
    Date July 1994
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    OBJECTIVE: The objective of this study was to compare perinatal outcomes of hypertensive and normotensive women experiencing abruptio placentae. Our hypothesis is that hypertensive women have a less favorable perinatal outcome than do normotensive women. STUDY DESIGN: Women with the diagnosis of abruptio placentae delivered between July 1, 1988, and May 31, 1992, composed the study group (n = 226) in this case-control study. The incidence of abruptio placentae was 0.7% during this time. Those women with either multifetal gestations (n = 4) or delivery before 20 weeks' gestation (n = 2) were excluded from data analysis. The remaining 220 patients were divided according to their hypertensive (n = 29) or normotensive (n = 191) status. Maternal and neonatal medical records were reviewed and abstracted for demographic variables, antepartum complications, delivery route, abruptio placentae grade, neonatal gender, birth weight, Apgar score, cord pH, and perinatal mortality. These perinatal outcome variables were compared between the hypertensive and normotensive patient groups. RESULTS: Black women with abruptio placentae were significantly more likely to be hypertensive (p = 0.0078). Hypertensive women with abruptio placentae had the antepartum complication diabetes mellitus significantly more often than did normotensive women (p = 0.032). However, they were similar to normotensive women with regard to the frequency of positive urine drug screen and trauma. Hypertensive women were no more likely to be delivered before 32 or 37 weeks' gestation, have neonates weighing < 1500 or 2500 gm, or to be delivered by cesarean section. Abruptio placentae grades 2 and 3 occurred more often in hypertensive women (p = 0.053), as did significantly lower umbilical cord artery (p = 0.005) and venous (p = 0.003) pH values. Neonates from hypertensive women were no more likely to have low 5-minute Apgar scores or to die than those from normotensive women. CONCLUSION: Although hypertensive women experiencing abruptio placentae are more likely to have higher-grade abruptio placentae and lower umbilical cord pH values, the overall perinatal outcome was not significantly different from that of normotensive women experiencing abruptio placentae.

    Title Intravenous Administration of Cocaine Stimulates Gravid Baboon Myometrium in the Last Third of Gestation.
    Date June 1994
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    The hypothesis for this investigation was that intravenous cocaine results in a dose-dependent increase in myometrial activity of the unanesthetized, chronically instrumented gravid nonhuman primate.

    Title Application of Backpropagation Neural Networks to Diagnosis of Breast and Ovarian Cancer.
    Date May 1994
    Journal Cancer Letters
    Excerpt

    Neural network programs have been developed in an attempt to improve the diagnosis of breast and ovarian cancer using a group of laboratory tests and the age of the patient. The laboratory tests employed in this study include albumin, cholesterol, HDL-cholesterol, triglyceride, apolipoproteins A1 and B, NMR linewidth (the Fossel Index) and a tumor marker (i.e., CA 15-3 or CA 125). The breast cancer study involved 104 patients (45 malignant and 59 benign subjects). The ovarian cancer study involved 98 individuals (35 malignant, 36 benign and 27 control subjects). Methods are outlined for identification of the most influential input parameters and optimization of network structure and training. Network characteristics were contrasted with the test results of the appropriate serum tumor marker assay. For the breast cancer study, the best neural network program, using six input parameters, had a sensitivity of only 55.6% and a specificity of 72.9%. The tumor marker CA 15-3 alone gave results of 61.3% and 64.4%, respectively. For the ovarian cancer study, the best neural network program, using six input parameters, had a sensitivity of 80.6% and a specificity of 85.5%. The tumor marker CA 125 alone gave results of 77.8% and 82.3%, respectively. These methods provide an objective approach to neural network optimization and parameter selection applicable to other data bases of clinical and laboratory data.

    Title Palliative Fetal Surgery for Diaphragmatic Hernia.
    Date April 1994
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    Congenital diaphragmatic hernia is associated with a poor prognosis in spite of advances in antenatal detection and newborn care. Open fetal surgery has been suggested as a strategy for salvaging selected fetuses at high risk for pulmonary hypoplasia as a result of this lesion. We report a strategy for palliative fetal surgery with definitive repair postponed to the newborn period.

    Title Massive Maternal Obesity and Perioperative Cesarean Morbidity.
    Date March 1994
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    OBJECTIVE: Our purpose was to determine the impact of massive maternal obesity (weight > 300 pounds) on perioperative morbidity among patients undergoing cesarean section. STUDY DESIGN: A case-control study was conducted on 43 massively obese pregnant women, identified by perinatal database search, who were delivered by cesarean section between Jan. 1, 1987, and Dec. 31, 1991, at Long Beach Memorial Women's Hospital. Forty-three randomly selected patients who underwent cesarean delivery served as the control group. Medical records were abstracted for perioperative variables and compared between groups. Student t test, chi 2, and Fisher's exact statistical analysis were used where appropriate. RESULTS: No significant differences were observed between groups for maternal age, parity, use of prophylactic antibiotics, length of recovery room stay, or wound dehiscence. The massively obese group was observed to be at significantly increased risk for emergency cesarean section (32.6% vs 9.3%, p = 0.02), prolonged delivery interval (25.6% vs 4.6%, p = 0.01), and total operative time (48.8% vs 9.3%, p < 0.0001), blood loss > 1000 ml (34.9% vs 9.3%, p = 0.009), multiple epidural placement failures (14.0% vs 0%, p = 0.02), postoperative endometritis (32.6% vs 4.9%, p = 0.002), and prolonged hospitalization (34.9% vs 2.3%, p = 0.0003). CONCLUSION: Massively obese pregnant women undergoing cesarean section are at significantly increased risk for perioperative morbidity.

    Title Extinction of Emotional Learning: Contribution of Medial Prefrontal Cortex.
    Date March 1994
    Journal Neuroscience Letters
    Excerpt

    Stimuli associated with painful or otherwise unpleasant events acquire aversive emotional properties in animals and humans. Subsequent presentation of the stimulus alone (in the absence of the unpleasant event) leads to the eventual extinction of the aversive reaction. Although the neural basis of emotional learning has been studied extensively, considerably less is known about the neural basis of emotional extinction. In the present study, we show that the medial prefrontal cortex plays an important role in the regulation of fear extinction in rats, a finding that may help elucidate the mechanisms and, possibly, the treatment of disorders of uncontrolled fear, such as anxiety, phobic, panic and posttraumatic stress disorders in humans.

    Title Influence of Labor and Route of Delivery on the Frequency of Respiratory Morbidity in Term Neonates.
    Date February 1994
    Journal International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics
    Excerpt

    OBJECTIVES: The purpose of this study is to compare the frequency of respiratory morbidity (RDS-Type I, RDS-Type II and PFC) in term neonates relative to three different delivery modes (cesarean delivery without labor, cesarean in labor, vaginal delivery). METHODS: A case-control study was performed consisting of 692 maternal/neonate pairs at term gestation with either a documented mature lung profile at an obstetrical age > or = 37 weeks' gestation or a Dubowitz age > or = 38 weeks' gestation. RESULTS: Overall, the frequency of neonatal respiratory morbidity was 5.1%. Neonatal respiratory morbidity was observed in 23 (12.4%) of 186 cases when cesarean delivery was performed prior to the onset of labor; in 10 (5.6%) of 177 cases when the cesarean delivery was performed after labor had ensued; and in 2 (0.6%) of 329 cases when the fetus was delivered vaginally (P < 0.001). CONCLUSION: The frequency of respiratory morbidity in term neonates is influenced by labor and route of delivery, and it is highest when cesarean delivery is performed prior to the onset of labor.

    Title Effects of Labetalol on Uterine Blood Flow and Cardiovascular Hemodynamics in the Hypertensive Gravid Baboon.
    Date June 1993
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    The purpose of this study was to investigate the effects of labetalol on uterine blood flow and cardiovascular parameters in acutely instrumented, hypertensive gravid baboons.

    Title Establishment of a Hydrogen Peroxide Resistant Variant of Renal Tubular Epithelial Cells: Role of Calcium-independent Phospholipase A2 in Cell Damage.
    Date March 1993
    Journal Archives of Biochemistry and Biophysics
    Excerpt

    Renal epithelial cells resistant to oxidant stress mediated by hydrogen peroxide have been isolated and characterized. African green monkey kidney epithelial cell line, BSC-1 cells, chronically exposed to 50 microM hydrogen peroxide for 15 passages exhibited increased catalase (1.5-fold) and glutathione peroxidase (2.4-fold) activity, as well as increased total cellular glutathione (1.6-fold). This was associated with the acquisition of resistance to hydrogen peroxide cytotoxicity, as judged by nuclear staining with ethidium homodimer and clonogenic survival assay. H2O2-adapted and wild-type BSC-1 cells were used to examine the role of elevated cytosolic calcium concentration and the activation of phospholipase A2 in the development of lethal cell injury. Despite dramatic differences in resistance to oxidative stress, both cell types showed similar kinetics of cytosolic calcium increase in response to challenge with hydrogen peroxide. In contrast to this, oxidant-induced release of arachidonic acid correlated with the resistance of both types of BSC-1 cells to oxidative stress. A mechanism-based inhibitor of calcium-independent phospholipase A2 (Hazen et al., J. Biol. Chem. 266, 7227, 1991) reduced oxidant-induced lethal cell injury, suggesting that this class of phospholipases contributes to damage of BSC-1 cells exposed to hydrogen peroxide. H2O2-adapted BSC-1 cells may represent a valuable tool to study adaptation to oxidative stress and various mechanisms of cell injury.

    Title Perinatal Outcome in Pregnancy Complicated by Massive Obesity.
    Date November 1992
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    OBJECTIVE: Our objective was to determine the impact of massive obesity during pregnancy, defined as maternal weight > 300 pounds, on perinatal outcome. STUDY DESIGN: A case-controlled study was conducted. Between Jan. 1, 1986, and Dec. 31, 1990, 111 pregnant women weighing > 300 pounds who were delivered at Long Beach Memorial Women's Hospital were identified with a perinatal data base search. A control group matched for maternal age and parity was selected, and perinatal variables were compared between groups. To control for potential confounding medical complications, massively obese patients with diabetes and/or chronic hypertension antedating the index pregnancy were excluded from the obese group, and the data were reanalyzed. The Student t test chi 2, and Fisher's exact statistical analysis were used where appropriate. RESULTS: Massively obese pregnant women are significantly more likely to have a multitude of adverse perinatal outcomes, including primary cesarean section (32.4% vs 14.3%, p = 0.002), macrosomia (30.2% vs 11.6%, p = 0.0001), intrauterine growth retardation (8.1% vs 0.9%, p = 0.03), and neonatal admission to the intensive care unit (15.6% vs 4.5%, p = 0.01). They also are significantly more likely to have chronic hypertension (27.0% vs 0.9%, p < 0.0001) and insulin-dependent diabetes mellitus (19.8% vs 2.7%, p = 0.0001). However, when those massively obese pregnant women with diabetes and/or hypertension antedating pregnancy are excluded from analysis, no statistically significant differences in perinatal outcome persisted. CONCLUSION: Massively obese pregnant women are at high risk for adverse perinatal outcome; however, this risk appears to be related to medical complications of obesity.

    Title Severity of Asthma and Perinatal Outcome.
    Date November 1992
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    OBJECTIVE: Our objective was to determine the impact of asthma and its severity, as determined by medication requirements, on perinatal outcome. STUDY DESIGN: A case-controlled study was conducted. Among 30,940 live births at Long Beach Memorial Medical Center Women's Hospital, 183 deliveries occurred between Jan. 1, 1985, and Dec. 31, 1990, that were coded for the diagnosis of asthma. Eighty-one that required the chronic use of medications to control their disease were identified. Thirty-one patients were steroid dependent and 50 were non-steroid-medication dependent. A control group was randomly selected (excluding maternal transports), and selected perinatal variables were compared between groups. RESULTS: When compared with controls, steroid-dependent asthmatics were at significantly increased risk for gestational (1.5% vs 12.9%) and insulin-requiring diabetes (0% vs 9.7%). Preterm delivery and preterm premature ruptured membranes occurred significantly more often in both asthmatic groups. Overall cesarean section rate was significantly increased in the non-steroid-medication-dependent asthmatic group when compared with controls (56.0% vs 30.0%). Delivery by primary cesarean section was significantly more common in the steroid-dependent group (38.7% vs 19.2%), and a strong trend was noted among the non-steroid-medication-dependent patients (34.0% vs 19.2%). Cesarean delivery for fetal distress was also more common in these two asthmatic groups. Neonates born to both groups of asthmatic pregnant women were significantly more likely to be of birth weight < 2500 gm but did not have an increased frequency of intrauterine growth restriction. No significant differences in low 5-minute Apgar scores were found; however, neonates born to both steroid-dependent and non-steroid-medication-dependent asthmatics were significantly more likely to be admitted to the neonatal intensive care unit (39.0% and 22.0% vs 7.7%). Preterm delivery and low birth weight were complications observed significantly more often in the steroid-dependent asthma group when compared with the non-steroid-medication-dependent group (54.8% vs 14.0% and 45.2% vs 14.0%). CONCLUSIONS: Perinatal outcome is compromised in the pregnancy complicated by chronic medication-dependent asthma. The extent is variable and is associated with disease severity, as measured by medication requirements.

    Title Septic Arthritis and Bacteremia Due to Mycoplasma Resistant to Antimicrobial Therapy in a Patient with Systemic Lupus Erythematosus.
    Date October 1992
    Journal Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America
    Excerpt

    We report a case of septic arthritis caused by Mycoplasma hominis in a patient with systemic lupus erythematosus. The infection started as monarthritis but spread to at least four joints despite apparently suitable therapy with various antimicrobial agents, including doxycycline, clindamycin, and ciprofloxacin; subsequent bacteremia was documented. Control was ultimately achieved with use of the experimental fluoroquinolone temafloxacin in combination with doxycycline administration, arthroscopic drainage of a persistently infected joint, several intravenous infusions of immunoglobulins (which led to increases in levels of antibodies specific to M. hominis), and discontinuation of corticosteroid therapy. Antimicrobial susceptibility testing of various mycoplasmal isolates showed the presence of the tetM gene, disparity between susceptibility to tetracycline and doxycycline, and increasing resistance to most antimicrobial agents used (including to fluoroquinolones before clinical use), although the patient ultimately had a favorable clinical response to treatment with combined modalities.

    Title Evaluation of the Fetal-pelvic Relationship.
    Date October 1992
    Journal Clinical Obstetrics and Gynecology
    Title Mild Oxidative Stress: Cellular Mode of Mitogenic Effect.
    Date September 1992
    Journal Renal Failure
    Title Department of Pharmacy-initiated Program for Streamlining Empirical Antibiotic Therapy.
    Date August 1992
    Journal Hospital Pharmacy
    Excerpt

    The outcome of a department of pharmacy-initiated "streamlining" study designed to promote cost-conscious modifications of empirically selected antibiotic therapy is described. Two hundred forty-one evaluable adult patients started on restricted-use antibiotics at this university-affiliated community private teaching hospital were enrolled in a 9-week prospective streamlining study. Patients were alternately assigned to a Control (i.e., no pharmacist-initiated streamlining recommendations offered based on culture and susceptibility reports) or a Pharmacist Intervention group (i.e., pharmacist offers recommendations to streamline therapy). A statistically significant greater number of patients had their empiric antibiotic treatment courses modified to more appropriate antibiotic choices after receipt of culture and susceptibility reports among private prescribers in the Pharmacist Intervention group (83%) than in the Control group (38%) (p = .006). Additionally, pharmacists were overall successful in gaining prescriber acceptance for 64% of recommended changes of empiric antibiotic treatment courses before the receipt of culture and susceptibility reports (e.g., dose and/or frequency changes). There was no program effect observed with respect to improved physician response to microbiologic data that would allow streamlining empirical antibiotic choices in the Housestaff (i.e., medical or surgical residents), or infectious disease consultant prescriber groups. Projected overall annual cost savings that would be achieved as a result of continued efforts by pharmacists directed at streamlining empirical "restricted" antibiotic regimens is approximately +40,000.

    Title Paranoid Schizophrenia May Be Caused by Dopamine Hyperactivity of Ca1 Hippocampus.
    Date June 1992
    Journal Biological Psychiatry
    Excerpt

    Explicit consolidation of memory, or fixation of declarative belief, appears to be physically represented in changes of synaptic conductances of neurons in the parietal-temporal-occipital association cortex (PTO) of the mammalian forebrain. This fixation of belief in PTO is postulated to be critically dependent on a diffuse reinforcement signal via the inferior temporal cortex (ITC) ultimately caused by an increased output of the CA1 pyramidal cells of hippocampus. Analogous to the reinforcing mechanisms of other forebrain systems, this updating of the connection weights of the neural nets in PTO by the output of the critical neurons in CA1 is directly related to concentrations of dopamine (DA). We propose that the delusions (i.e., unreasonable beliefs) of paranoid schizophrenia are caused by a hyperactivity of the same DA-sensitive CA1 neurons that are responsible for the fixation of normal beliefs. The dramatic reduction in delusions with administration of neuroleptics, as DA D2 blockers, in schizophrenics may thus be explained by their acting to ameliorate the hyperactivity of these CA1 DA D2 receptors.

    Title Efficacy of the Fetal-pelvic Index in Nulliparous Women at High Risk for Fetal-pelvic Disproportion.
    Date April 1992
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    OBJECTIVE: The null hypothesis of this study is that the fetal-pelvic index will not determine the presence or absence of fetal-pelvic disproportion in 137 nulliparous women at high risk for fetal-pelvic disproportion. STUDY DESIGN: This study was undertaken by comparing the blinded fetal-pelvic index values and two other methods of identifying fetal-pelvic disproportion, ultrasonography-derived estimated fetal weight greater than or equal to 4000 gm and Mengert's index, to delivery outcomes in 137 nulliparous women at high risk for fetal-pelvic disproportion. RESULTS: After adequate labor trials, 55 of 73 patients who required operative intervention had a positive fetal-pelvic index (sensitivity = 75%). Seventeen of the 18 patients with a false-negative fetal-pelvic index value had persistent malpositions (15 occipitoposterior, 1 occipitotransverse, and 1 face presentation). Spontaneous vaginal deliveries occurred in 64 patients with 62 of them having a negative fetal-pelvic index (specificity 97%). The overall predictability of the fetal-pelvic index in this patient population was 85% and the positive predictability was 96%. However, neither ultrasonography-derived estimated fetal weight nor x-ray pelvimetry, when used alone, accurately detected the presence or absence of fetal-pelvic disproportion in nulliparous women at high risk for the condition. CONCLUSION: The fetal-pelvic index is efficacious in determining the presence or absence of fetal-pelvic disproportion in nulliparous women at high risk for the condition.

    Title Extended-field Radiation Therapy in Early-stage Cervical Carcinoma: Survival and Complications.
    Date January 1992
    Journal Gynecologic Oncology
    Excerpt

    Four hundred fifteen patients with early-stage cervical carcinoma were explored via a transperitoneal approach for radical hysterectomy at the Hospital of the University of Pennsylvania between January 1, 1960, and December 31, 1985. Twenty-four of these patients were found to have histologic documentation of para-aortic lymph node metastases. Twenty-one patients (88%) were treated primarily with extended-field radiotherapy. Forty-eight percent of these patients have survived greater than 5 years from diagnosis. Six patients have been followed more than 10 years after initial treatment. All six are alive although one patient has recurrent disease that was diagnosed at 164 months. Patients with adenocarcinoma or adenosquamous carcinoma had a survival significantly lower than that of those with squamous cell cancers (p = 0.022). Complications included one treatment-related death from multiple fistulas and sepsis, one vesicovaginal fistula, two enteric fistulas, and two small bowel obstructions. The major morbidity rate was 19%. Extended-field radiation is effective therapy for para-aortic nodal metastasis associated with early-stage squamous cell carcinomas of the cervix but carries a considerable morbidity rate. Other modalities such as combined chemotherapy and radiation may be necessary for adenocarcinoma.

    Title A Statement of Assumptions and Principles Concerning Education About Life-threatening Illness, Death, Dying, and Bereavement for Volunteers and Non-professionals. International Work Group on Death, Dying and Bereavement.
    Date November 1991
    Journal The American Journal of Hospice & Palliative Care
    Title The Fetal-pelvic Index: a Method of Identifying Fetal-pelvic Disproportion in Women Attempting Vaginal Birth After Previous Cesarean Delivery.
    Date September 1991
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    In 1986 the fetal-pelvic index was introduced as an accurate method of prospectively identifying the presence or absence of fetal-pelvic disproportion. The concept of the fetal-pelvic index is one in which the fetal head and abdominal circumferences (ultrasonographic mensuration) are compared with the respective maternal pelvic inlet and midpelvic circumferences (x-ray pelvimetry). The purpose of this study is to evaluate the efficacy of this index as a predictor of fetal-pelvic disproportion in gravid women attempting vaginal birth after previous cesarean delivery. Findings of the fetal-pelvic index are compared with those of two other means of identifying fetal-pelvic disproportion (Colcher-Sussman x-ray pelvimetry and ultrasonographically derived estimated fetal weight of greater than or equal to 4000 gm). Of the 65 prospective study participants, 18 (28%) failed to progress in labor, and a repeat cesarean delivery was required. Forty-seven of the 52 patients with a negative fetal-pelvic index value were delivered vaginally (negative predictability = 0.90). Of the five with false-negative fetal-pelvic index values, four fetuses persisted in an occipitoposterior position and failed to progress in labor. All 13 patients with a positive fetal-pelvic index value failed to progress in labor and required a cesarean delivery (positive predictability = 1.00). In contrast, when used alone, neither x-ray pelvimetry nor ultrasonography-determined estimated fetal weight of greater than or equal to 4000 gm provided accurate identification of fetal-pelvic disproportion.

    Title Tetrasomy of the Short Arm of Chromosome 9: Prenatal Diagnosis and Further Delineation of the Phenotype.
    Date August 1991
    Journal American Journal of Medical Genetics
    Excerpt

    A fetus with multiple malformations was identified by prenatal ultrasound investigation. Cordocentesis and fetal lymphocyte chromosome analysis demonstrated a model number of 47 chromosomes. The extra chromosome material was identified as an isochromosome of the entire short arm of chromosome 9 with no involvement of the heterochromatic region of the long arm [47,XY, + i(9p)]. This represents the first report of prenatal diagnosis of tetrasomy 9p. Further delineation of the phenotype is discussed.

    Title Treatment of Advanced and Recurrent Endometrial Cancer with Cisplatin, Doxorubicin, and Cyclophosphamide.
    Date July 1991
    Journal Gynecologic Oncology
    Excerpt

    Twenty-five patients with recurrent or advanced-stage endometrial cancer were treated with cisplatin, doxorubicin, and cyclophosphamide (PAC) from May 1982 to November 1987. A retrospective chart analysis was performed to evaluate the effect of treatment on survival and progression-free interval. Toxicity was moderate. Neutropenia was the most common side effect. Age, performance status, and tumor cytoreduction were statistically significant predictors of survival time (P less than 0.03). In the 17 evaluable patients, the response rate was 47%. PAC is an active regimen in the treatment of endometrial cancer. Larger prospective studies are needed to evaluate whether tumor cytoreduction is important in the treatment of this disease.

    Title Effect of Intravenous Cocaine on Uterine Blood Flow in the Gravid Baboon.
    Date May 1991
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    Cocaine abuse during pregnancy is associated with adverse perinatal outcome, believed to be a result of potent vasoconstrictive effects that cocaine has on the maternal cardiovascular system. The direct effect of cocaine on the pregnant, nonhuman primates' uterine vasculature in vivo has not been examined. We investigated the effects of intravenous cocaine on maternal arterial blood pressure, uterine blood flow, and uterine vascular resistance in four unanesthetized, chronically instrumented pregnant baboons. Baboons were instrumented during the latter half of pregnancy, placing an ultrasonic flow probe around one uterine artery and catheters in the maternal inferior vena cava and aorta. Bolus intravenous cocaine hydrochloride doses of 0.05 mg/kg, 0.1 mg/kg, and 0.3 mg/kg by maternal weight were infused 30 minutes apart at least 5 days after surgical instrumentation. The maternal blood pressure rose 7.3% and 12.0% after the 0.1 mg/kg and 0.3 mg/kg cocaine infusions, respectively, and the uterine blood flow fell in a dose-dependent fashion 13.1% and 22.7%. Plasma norepinephrine levels rose in response to the 0.3 mg/kg cocaine infusion. These studies show that low doses of cocaine significantly reduce uterine blood flow in the pregnant baboon in a dose-dependent manner by increasing uterine vascular resistance.

    Title Management and Outcome of Two Pregnancies in a Woman with Craniodiaphyseal Dysplasia.
    Date February 1991
    Journal American Journal of Perinatology
    Excerpt

    Hyperostotic bone dysplasias are characterized by progressive hyperostosis and sclerosis of the cranium and facial bones. As a result of progressive bony overgrowth, intracranial pressure may increase and lead to brain and nerve compression, cranial nerve palsies, and an increased incidence of seizures. The long bones often exhibit defective modeling as well as variable degrees of metaphyseal and diaphyseal hyperostosis. In addition, the axial skeleton (including the pelvis) is often hyperostotic and sclerotic. The clinical features of these disorders may have relevance to the outcome of pregnancy; however, there are no reports on the management and pregnancy outcome of patients affected with hyperostotic bone disease. In this report, we describe the course of two pregnancies in a woman with craniodiaphyseal dysplasia (a rare craniotubular dysplasia). Prenatal assessment, method of delivery, choice of anesthesia, and neonatal management are discussed. Although this disorder is rare, the pathophysiologic considerations relevant to pregnancy outcome may be applicable to the management of pregnant women with other hyperostotic bone dysplasias.

    Title Electrocardiographic Abnormalities During Ritodrine Administration.
    Date June 1990
    Journal Southern Medical Journal
    Excerpt

    Electrocardiographic abnormalities have been reported during ritodrine tocolysis. No previous studies, however, have included controls. The purpose of this study is to evaluate the electrocardiographic tracings of patients receiving ritodrine tocolysis and compare them with those of matched controls. Holter monitors were placed on eight patients receiving ritodrine tocolysis and eight control patients for 24 hours to make continuous electrocardiographic records. Twelve-lead electrocardiograms, serum glucose, and electrolyte concentrations were monitored serially in all patients. Four of the eight patients receiving ritodrine tocolysis demonstrated ST segment depression, while none of the control patients manifested any electrocardiographic abnormalities. The observed ST segment depression appears to be related to the degree of maternal tachycardia and the level of hypokalemia and hyperglycemia that occurs during early ritodrine tocolysis.

    Title Vaginal and Bladder Angiosarcoma After Therapeutic Irradiation.
    Date December 1989
    Journal Southern Medical Journal
    Excerpt

    Angiosarcoma involving the female genitourinary tract is a rare soft tissue malignancy of vascular origin. We have described probably the first reported case of postirradiation angiosarcoma involving the vagina and bladder, and have reviewed the existing literature on the subject of angiosarcoma resulting from previous therapeutic irradiation for gynecologic malignancy.

    Title Bilateral Simultaneous Tubal Pregnancy: Case Report and Review of the Literature.
    Date June 1989
    Journal Obstetrical & Gynecological Survey
    Title Treatment of Stage Ii Endometrial Carcinoma.
    Date May 1989
    Journal Gynecologic Oncology
    Excerpt

    The optimal management of stage II carcinoma of the endometrium remains to be established. We reviewed our experience in treating 42 patients with stage II endometrial cancer by surgery, radiation, or combined radiation and surgery at the Hospital of the University of Pennsylvania. The overall 5-year survival was 47.6%. The 5-year survivals of patients treated by surgery only, radiation only, or combination radiation and surgery were 68.5, 36.5, and 46.1%, respectively, which were not significantly different. Histologic grade was found a significant prognostic factor but type of cervical involvement was not. Major complication rates were similar in each treatment group. We conclude that the majority of patients with stage II endometrial carcinoma are best treated by combination radiation and surgery, but in a select subset of patients, radical hysterectomy and lymphadenectomy constitute a reasonable treatment option.

    Title Antenatal Diagnosis of Candida Chorioamnionitis.
    Date March 1989
    Journal Southern Medical Journal
    Title Efficacy of the Fetal-pelvic Index As a Predictor of Fetal-pelvic Disproportion in Women with Abnormal Labor Patterns That Require Labor Augmentations.
    Date December 1988
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    The fetal-pelvic index, which compares fetal head and abdomen circumferences with respective maternal inlet and midpelvic circumferences, was introduced in 1986 as a means of identifying the presence or absence of fetal-pelvic disproportion. In this study the efficacy of the fetal-pelvic index was evaluated in 46 patients with abnormal labor patterns that required labor augmentations and was compared with that of two other means (Colcher-Sussman x-ray pelvimetry and ultrasonographically derived estimated fetal weight greater than or equal to 4000 gm). Of the 24 women who required operative intervention (19 cesarean sections and five operative vaginal procedures), 17 had positive fetal-pelvic index values (sensitivity = 0.71). Six of the seven fetuses of patients with false-negative fetal-pelvic index values persisted in an occipitoposterior presentation, and these patients failed to progress in labor. Of the 22 patients in whom vaginal deliveries were spontaneous, 21 had negative fetal-pelvic index values (specificity = 0.95). Of the 18 women with positive fetal-pelvic index values, 17 required operative intervention (positive predictability = 0.94). In contrast, when used alone, neither x-ray pelvimetry nor ultrasonographically derived estimated fetal weight greater than or equal to 4000 gm provided accurate identification of fetal-pelvic disproportion.

    Title Efficacy of the Fetal-pelvic Index in Patients Requiring Labor Induction.
    Date October 1988
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    The fetal-pelvic index is a recently described means of identifying the presence or absence of fetal-pelvic disproportion. In this follow-up study, the efficacy of the fetal-pelvic index was evaluated in 49 patients requiring labor induction and was compared with two other methods used to identify fetal-pelvic disproportion (Colcher-Sussman x-ray pelvimetry and ultrasound-derived estimated fetal weight). Twelve of 14 patients who required operative intervention also demonstrated a positive fetal-pelvic index (sensitivity = 86%). Spontaneous vaginal deliveries occurred in 35 patients, all of whom demonstrated negative fetal-pelvic index values (specificity = 100%). Overall the predictability of the fetal-pelvic index was 96%. In comparison, when used alone, neither x-ray pelvimetry nor ultrasound-derived estimated fetal weight accurately detected the presence or absence of fetal-pelvic disproportion in patients requiring labor induction.

    Title Efficacy of the Fetal-pelvic Index for Delivery of Neonates Weighing 4000 Grams or Greater: a Preliminary Report.
    Date June 1988
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    The fetal-pelvic index was recently introduced as an accurate method of prospectively identifying the presence or absence of fetal-pelvic disproportion. In that report the ability to detect fetal-pelvic disproportion in patients with macrosomic fetuses was not specifically addressed. The objective of this study is to compare the efficacy of three methods used to identify the presence or absence of fetal-pelvic disproportion (the fetal-pelvic index, Colcher-Sussman x-ray pelvimetry, and estimated fetal weight greater than or equal to 4000 gm) in patients delivered of neonates weighing greater than or equal to 4000 gm after an adequate trial of labor (N = 34). Of the 18 patients requiring operative intervention, all but one had a positive fetal-pelvic index value (sensitivity = 94%). Of the 16 patients in whom vaginal deliveries were spontaneous, all but one had a negative value (specificity = 94%). On the basis of these data, the fetal-pelvic index is an accurate method of predicting the presence or absence of fetal-pelvic disproportion in patients delivered of neonates weighing greater than or equal to 4000 gm.

    Title Pregnancy-induced Hypertension Without Proteinuria: is It True Preeclampsia?
    Date March 1988
    Journal Southern Medical Journal
    Excerpt

    A profile scoring system has recently been developed as a standardized method of early identification and severity assessment of pregnancy-induced hypertension (PIH). The purpose of this study is twofold: (1) to compare the PIH profile scores of patients demonstrating mild PIH without proteinuria with those of patients demonstrating mild PIH with proteinuria, and (2) to introduce the PIH profile graph as a standardized clinical assessment tool. Serial PIH profile data after 24 weeks' gestation from 46 term primigravid patients with mild PIH (group 1 = 19 patients without proteinuria; group 2 = 27 patients with proteinuria) were plotted on PIH profile graphs and compared. Profile scores from ten normotensive primigravidas at term served as controls. Serial profile scores for groups 1 and 2 showed similar patterns on the profile graph. Based on these data, we believe that PIH without proteinuria is clinically and biochemically a manifestation of true preeclampsia before the onset of proteinuria. Furthermore, the PIH profile graph allows one to identify subtle changes in the disorder and to anticipate the development of severe preeclampsia.

    Title Plasma Fibronectin Levels in Normal Pregnancy and Pre-eclampsia: a Preliminary Report.
    Date February 1988
    Journal International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics
    Excerpt

    Fibronectin, a major component of the extracellular matrix and basement membranes throughout the body, is thought to maintain the integrity of both the reticulo-endothelial system and microvasculature. In this study, plasma fibronectin levels were assayed by nephelometry in nine pre-eclamptic gravid women, nine normotensive gravid women and ten non-gravid women. The mean plasma fibronectin level (+/-S.E.M.) in pre-eclamptic gravidas (1687 +/- 101 micrograms/ml) is significantly higher than that of either normotensive gravidae (1129 +/- 99 micrograms/ml) or non-gravid women (897 +/- 60 micrograms/ml). Although the mechanism for elevated levels of plasma fibronectin in patients with pre-eclampsia is not clear, it may serve as an early biochemical marker for this disorder.

    Title Uterus Didelphys with Unilateral Hematocolpos, Ipsilateral Renal Agenesis and Menses. A Case Report and Literature Review.
    Date May 1987
    Journal The Journal of Reproductive Medicine
    Excerpt

    A 13-year-old girl with signs and symptoms of an acute abdomen was found to have uterus didelphys, unilateral hematocolpos, ipsilateral renal agenesis and menses. A review of the literature in English revealed 115 reported cases. This complex congenital anomaly is seen most commonly in adolescents with dysmenorrhea of progressive severity, abdominal pain and a pelvic mass.

    Title Failure of Rapid Agglutination Methods to Detect Oxacillin-resistant Staphylococcus Aureus.
    Date November 1986
    Journal Journal of Clinical Microbiology
    Excerpt

    Although a latex agglutination test (StaphAurex) and a hemagglutination test (Staphyloslide) correctly identified all strains of Staphylococcus aureus that were susceptible or had intermediate susceptibility to oxacillin, 17 of 73 (23%) and 18 of 73 (25%) strains of oxacillin-resistant S. aureus were not identified by StaphAurex and Staphyloslide, respectively. All strains not detected were resistant to trimethoprim-sulfamethoxazole and rifampin.

    Title The Fetal-pelvic Index As an Indicator of Fetal-pelvic Disproportion: a Preliminary Report.
    Date October 1986
    Journal American Journal of Obstetrics and Gynecology
    Excerpt

    The objective of this study was to develop a standardized method of identifying fetal-pelvic disproportion by comparing fetal head and abdomen circumferences with the respective maternal pelvic inlet and midpelvis circumferences. Fetal ultrasound and maternal x-ray pelvimetry measurements were performed on 75 term pregnant women with indications for a trial of labor. By means of individually measured fetal and maternal pelvic diameters, circumferences of the fetal head, fetal abdomen, maternal pelvic inlet, and maternal midpelvis were computed. Based on four circumference differences between the fetus and maternal pelvis (fetal head--maternal pelvic inlet, fetal head--maternal midpelvis, fetal abdomen--maternal pelvic inlet, and fetal abdomen--maternal midpelvis), a fetal pelvic index number was derived from the sum of the two most positive values. Of the 27 patients requiring cesarean sections for failure to progress in labor, all but four had positive fetal pelvic index values (sensitivity = 85%). Of the 48 patients who were delivered vaginally, all but four had negative fetal pelvic index values (specificity = 92%).

    Title Effect of Short-duration Constant Exercise on Permeability of Cockerel Aorta to 125i-albumin.
    Date December 1985
    Journal Journal of Applied Physiology (bethesda, Md. : 1985)
    Excerpt

    To determine quantitatively the effect of short duration constant exercise on the rate of uptake (U) of intravenously injected 125I-labeled cockerel albumin (A) by the aorta of the adult cockerel, 24 birds divided into age-matched pairs, each pair consisting of an exercised and nonexercised control bird, were studied. The time period of heparinization, anesthesia, and time from injection of A (each member of each pair received about 50 microCi from the same batch) to the death of the animal (T) was identical for each member of each pair. The exercised animal was exercised at a constant speed of 3.2 kph at 0 degrees elevation for between 2 and 5 min on a treadmill. U was defined as accumulated wall radioactivity (dpm)/plasma radioactivity (dpm/ml) X endothelial surface area (cm2) X T (s). Free 125I in the injectate amounted to 1.29 +/- 0.31% (mean +/- SD). Free 125I in the plasma and the wall in the exercise and control animals was not significantly different: plasma 0.84 +/- 0.34% (mean +/- SD) and 0.55 +/- 0.18 (P less than 0.20); wall 3.38 +/- 5.64% and 6.42 +/- 4.72 (P less than 0.04). Injected A remaining in the blood at between 8 and 16 min after intravenous injection was 83 +/- 8.7% (n = 10) in the exercised and 82 +/- 10% (n = 7) in the control (P less than 0.2). U was greater in the exercise group in 9 out of 12 matched pairs (P less than 0.05). We conclude that U increases for short periods of constant exercise.

    Title Disseminated Sporotrichosis with Sporothrix Schenckii Fungemia.
    Date June 1984
    Journal Diagnostic Microbiology and Infectious Disease
    Excerpt

    The laboratory diagnosis and therapeutic management of disseminated sporotrichosis can present many problems to the clinical laboratory and the clinician. Culturing of clinical specimens is necessary because the direct microscopic examination of specimens for Sporothrix schenckii often is not useful. Although this organism has been recovered from many specimen sites, recovery from blood has been rare. This report summarizes data concerning recovery of S. schenckii from clinical specimens and the use of serologic and fungal antimicrobial susceptibility data. It appears to be the first antemortem recovery of S. schenckii from blood reported since 1909.

    Title An Extracellular H2o2-requiring Enzyme Preparation Involved in Lignin Biodegradation by the White Rot Basidiomycete Phanerochaete Chrysosporium.
    Date October 1983
    Journal Biochemical and Biophysical Research Communications
    Excerpt

    An H2O2-requiring enzyme system was found in the extracellular medium of ligninolytic cultures of Phanerochaete chrysosporium. The enzyme system generated ethylene from 2-keto-4-thiomethyl butyric acid (KTBA), and oxidized a variety of lignin model compounds including the diarylpropane 1-(4'-ethoxy-3'-methoxyphenyl) 1,3-dihydroxy-2-(4"-methoxyphenyl)propane (I), a beta-ether dimer 1-(4'-ethoxy-3'-methoxyphenyl)glycerol-beta-guaiacyl ether (IV) and an olefin 1-(4'-ethoxy-3'-methoxyphenyl)1,2-propene (VI). The products found were equivalent to the metabolic products previously isolated from intact ligninolytic cultures. In addition, the enzyme system partially degraded 14C-ring labeled lignin. The enzyme was not found in high nitrogen (N) cultures, nor in cultures of a ligninolytic mutant strain which is incapable of metabolizing lignin.

    Title Degradation of the Gamma-carboxyl-containing Diarylpropane Lignin Model Compound 3-(4'-ethoxy-3'-methoxyphenyl)-2-(4''-methoxyphenyl)propionic Acid by the Basidiomycete Phanerochaete Chrysosporium.
    Date
    Journal Applied and Environmental Microbiology
    Excerpt

    The white-rot basidiomycete Phanerochaete chrysosporium metabolized 3-(4'-ethoxy-3'-methoxyphenyl)-2-(4''-methoxyphenyl)propionic acid (V) in low-nitrogen, stationary cultures, conditions under which ligninolytic activity is expressed. The ability of several fungal mutant strains to degrade V reflected their ability to degrade [C]lignin to CO(2). 1-(4'-Ethoxy-3'-methoxyphenyl)-2-(4''-methoxyphenyl)-2- hydroxyethane (VII), anisyl alcohol, and 4-ethoxy-3-methoxybenzyl alcohol were isolated as metabolic products, indicating an initial oxidative decarboxylation of V, followed by alpha, beta cleavage of the intermediate (VII). Exogenously added VII was rapidly converted to anisyl alcohol and 4-ethoxy-3-methoxybenzyl alcohol. When the degradation of V was carried out under O(2), O was incorporated into the beta position of the diarylethane product (VII), indicating that the reaction is oxygenative.

    Title Radiotherapy Combined with Gemcitabine and Oxaliplatin in Pancreatic Cancer Cells.
    Date
    Journal Translational Oncology
    Excerpt

    Clinical evidence suggests that gemcitabine (Gem) plus oxaliplatin (Ox) is superior to gemcitabine alone in advanced pancreatic carcinoma. The addition of radiation to gemcitabine improves response and is a standard treatment for locally advanced disease. We investigated the effect of oxaliplatin on gemcitabine-based chemoradiation by determining whether gemcitabine and oxaliplatin produced synergistic cytotoxicity using median effect analysis and radiosensitization using clonogenic survival assays. We analyzed the effects of gemcitabine and oxaliplatin on cell cycle distribution by DNA content and on radiation-induced DNA damage repair by phosphorylated H2AX (gamma-H2AX). Gemcitabine and oxaliplatin produced schedule-dependent synergistic cytotoxicity in BxPC-3 and Panc-1 cells (combination indices: 0.76 +/- 0.05, 0.61 +/- 0.11). In BxPC-3 cells, oxaliplatin did not affect gemcitabine-mediated radiosensitization (Gem 1.99 +/- 0.27; Gem + Ox 2.38 +/- 0.30). In Panc-1 cells, oxaliplatin significantly enhanced gemcitabine-mediated radiosensitization (Gem 1.31 +/- 0.05; Gem + Ox 2.90 +/- 0.31). Radiosensitization by gemcitabine was accompanied by early S-phase arrest and induction/persistence of gamma-H2AX protein, which were unaltered by oxaliplatin. Addition of oxaliplatin to gemcitabine produces radiosensitization equal to or greater than gemcitabine alone, supporting our clinical investigation of oxaliplatin with gemcitabine-radiation in pancreatic cancer aimed at improving systemic disease control while maintaining local tumor radiosensitization.

    Title Chronic Corticosterone Administration Does Not Potentiate Unconditioned Freezing to the Predator Odor, Trimethylthiazoline.
    Date
    Journal Behavioural Brain Research
    Excerpt

    Chronic high levels of corticosterone (CORT) are known to facilitate learning and memory of aversive events. Whether this effect of chronic CORT also generalizes to unconditioned or unlearned fear behavior is not known. The present study investigated whether high levels of chronic CORT enhance unconditioned fear to a predator odor, trimethylthiazoline (TMT), an innate fear stimulus to rodents. TMT induces a dose-related freezing response, a prototypical behavior to fearful stimuli, in rats. The first experiment demonstrated that dose-related freezing to repeated exposures of TMT does not habituate, sensitize or produce contextually conditioned fear, and therefore can be used to measure the effects of chronic CORT on unconditioned fear to repeated exposures of TMT. In Experiment 2, 21-day release corticosterone pellets (200mg) were implanted subcutaneously in male, Sprague-Dawley rats. Control rats received sham implantation. On days when TMT was not present, chronic CORT rats froze significantly more than sham rats. However, while TMT-induced freezing in both chronic CORT and sham rats, freezing during exposure to TMT was not further enhanced in chronic CORT rats. Thus, chronic CORT appears to increase fear as measured by freezing, possibly by enhancing vigilance, but does not facilitate fear behavior induced by the innate fear stimulus, TMT.

    Title Comment on Wall Et Al.: "ethical Aspects of Urinary Diversion for Women with Irreparable Obstetric Fistulas in Developing Countries"
    Date
    Journal International Urogynecology Journal and Pelvic Floor Dysfunction
    Title Rbx1 (ring Box Protein 1) E3 Ubiquitin Ligase is Required for Genomic Integrity by Modulating Dna Replication Licensing Proteins.
    Date
    Journal The Journal of Biological Chemistry
    Excerpt

    RBX1 (RING box protein 1), also known as ROC1 (Regulator of Cullin 1), is an essential component of SCF (Skp1/Cullins/F-box) E3 ubiquitin ligases, which target diverse proteins for proteasome-mediated degradation. Our recent study showed that RBX1 silencing triggered a DNA damage response (DDR) leading to G(2)-M arrest, senescence, and apoptosis, with the mechanism remaining elusive. Here, we show that, in human cancer cells, RBX1 silencing causes the accumulation of DNA replication licensing proteins CDT1 and ORC1, leading to DNA double-strand breaks, DDR, G(2) arrest, and, eventually, aneuploidy. Whereas CHK1 activation by RBX1 silencing is responsible for the G(2) arrest, enhanced DNA damage renders cancer cells more sensitive to radiation. In Caenorhabditis elegans, RBX-1 silencing causes CDT-1 accumulation, triggering DDR in intestinal cells, which is largely abrogated by simultaneous CDT-1 silencing. RBX-1 silencing also induces lethality during development of embryos and in adulthood. Thus, RBX1 E3 ligase is essential for the maintenance of mammalian genome integrity and the proper development and viability in C. elegans.

    Title Bayesian Hierarchical Changepoint Methods in Modeling the Tumor Growth Profiles in Xenograft Experiments.
    Date
    Journal Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
    Excerpt

    PURPOSE: The standard approach of using tumor doubling time to assess growth delay may not accurately represent tumor response, especially if the growth rates are not constant. Therefore, we developed a method to compare the antitumor activities of different treatments in xenograft experiments that uses the entire growth curve to estimate non-constant growth rates.EXPERIMENTAL DESIGN: A Bayesian hierarchical changepoint (BHC) method was used to model logarithmically transformed tumor volumes. Each tumor was assumed to have a growth profile, represented by a pre-nadir regression rate, a regression period, a nadir volume, and a post-nadir regrowth rate. Confidence intervals were calculated to compare these features between different treatments. We used data from a study assessing the effects of radiation, gemcitabine, and a Chk1/2 inhibitor on MiaPaCa-2 xenografts.RESULTS: We found that the BHC model provided a good fit to the data and more descriptive features than the tumor doubling approach. This model detected significant tumor regression in the AZD7762+1Gy and GEM+1Gy that was not detected when comparing the tumor doubling times. The BHC model also provided evidence that the growth inhibition resulted from a direct tumor effect rather than an indirect effect on the tumor bed, as evidenced by dramatic tumor regression in response to effective treatments and similar post-nadir regrowth rates across all treatment groups.CONCLUSIONS: Compared with the tumor doubling time approach, the BHC model utilizes all data, providing more descriptive features that address mechanisms underlying tumor growth inhibition and maximize the biological information obtained from tumor xenografts studies.

    Title Cancer Patients with Pain: the Spouse/partner Relationship and Quality of Life.
    Date
    Journal Cancer Nursing
    Excerpt

    A diagnosis of cancer affects not only the patient but also his/her spouse/partner. In addition to facing a life-threatening illness, changes in role and financial threats can impact the dyad.

    Title Cervical Cancer Screening.
    Date
    Journal Journal of the National Comprehensive Cancer Network : Jnccn
    Excerpt

    Overview Despite a significant decrease in the incidence and mortality of cervical carcinoma in the United States, an estimated 12,200 women will be diagnosed with the disease in 2010, with 4210 expected deaths.(1) High-risk groups include women without access to health care and those who have immigrated to the United States from countries where cervical cancer screening is not routinely performed.(2) Because cervical cytology screening is the current method for early detection of this neoplasm, the purpose of these guidelines is to provide direction for the evaluation and management of cervical cytology. These guidelines include recommendations on screening techniques, initiation, and frequency of screening, and management of abnormal screening results including colposcopy. Cervical cytology screening techniques include liquid-based cytology or conventional Papanicolaou (Pap) smears. Unless specifically noted, these techniques are collectively referred to as cervical cytology in this discussion. Human papillomavirus (HPV) DNA testing for primary cervical cancer has been approved by the FDA; several diagnostic tests are available (e.g., HPV high-risk and HPV 16/18 DNA tests, Hybrid Capture 2 HPV DNA test). However, HPV DNA testing is not recommended in women younger than 21 years.(3) HPV DNA testing for high-risk virus types can also be used as a component of both primary screening and workup of abnormal cytology results; it is not useful to test for low-risk virus types.(3) (See HPV DNA Testing on page 1378 for more detail about these tests.) Colposcopy, along with colposcopically directed biopsies, is the primary method for evaluating women with abnormal cervical cytologies....

    Title Cervical Cancer.
    Date
    Journal Journal of the National Comprehensive Cancer Network : Jnccn
    Excerpt

    Overview An estimated 12,200 new cases of cervical cancer will be diagnosed in the United States in 2010, and 4200 people will die of the disease.(1) Cervical cancer rates are decreasing among women in the United States, although incidence remains high among Hispanic/Latino, black, and Asian women.(2-5) However, cervical cancer is a major world health problem for women. The global yearly incidence of cervical cancer for 2002 was 493,200; the annual death rate was 273,500. It is the third most common cancer in women worldwide,(6,7) with 78% of cases occurring in developing countries, where cervical cancer is the second most frequent cause of cancer death in women. Persistent human papillomavirus (HPV) infection is regarded as the most important factor contributing to the development of cervical cancer. A relationship seems to exist between the incidence of cervical cancer and the prevalence of HPV in the population. The prevalence of chronic HPV in countries with a high incidence of cervical cancer is 10% to 20%, whereas its prevalence in low-incidence countries is 5% to 10%.(6) Immunization against HPV prevents infection with certain types of HPV and, thus, is expected to prevent specific HPV cancer in women (see NCCN Clinical Practice Guidelines in Oncology [NCCN Guidelines] for Cervical Cancer Screening, in this issue; to view the most recent version of these guidelines, visit the NCCN Web site at www.NCCN.org).(8-12) Other epidemiologic risk factors associated with cervical cancer are a history of smoking, parity, contraceptive use, early age at onset of coitus, larger number...

    Title Modulation of Anthracycline-induced Cytotoxicity by Targeting the Prenylated Proteome in Myeloid Leukemia Cells.
    Date
    Journal Journal of Molecular Medicine (berlin, Germany)
    Excerpt

    Deregulation of Ras/ERK signaling in myeloid leukemias makes this pathway an interesting target for drug development. Myeloid leukemia cell lines were screened for idarubicin-induced apoptosis, cell-cycle progression, cell-cycle-dependent MAP kinase kinase (MEK-1/2) activation, and Top2 expression. Cell-cycle-dependent activation of MEK/ERK signaling was blocked using farnesyltransferase inhibitor (FTI) BMS-214,662 and dual prenyltransferase inhibitor (DPI) L-778,123 to disrupt Ras signaling. Idarubicin caused a G2/M cell-cycle arrest characterized by elevated diphosphorylated MEK-1/2 and Top2α expression levels. The FTI/DPIs elicited distinct effects on Ras signaling, protein prenylation, cell cycling and apoptosis. Combining these FTI/DPIs with idarubicin synergistically inhibited proliferation of leukemia cell lines, but the L-778,123+idarubicin combination exhibited synergistic growth inhibition over a greater range of drug concentrations. Interestingly, combined FTI/DPI treatment synergistically inhibited cell proliferation, induced apoptosis and nearly completely blocked protein prenylation. Inhibition of K-Ras expression by RNA interference or blockade of its post-translational prenylation led to increased BMS-214,662-induced apoptosis. Our results suggest that nearly complete inhibition of protein prenylation using an FTI + DPI combination is the most effective method to induce apoptosis and to block anthracycline-induced activation of ERK signaling.

    Title Phase I/ii Randomized Trial of Dendritic Cell Vaccination with or Without Cyclophosphamide for Consolidation Therapy of Advanced Ovarian Cancer in First or Second Remission.
    Date
    Journal Cancer Immunology, Immunotherapy : Cii
    Excerpt

    In spite of increased rates of complete response to initial chemotherapy, most patients with advanced ovarian cancer relapse and succumb to progressive disease. Immunotherapy may have potential for consolidation therapy.

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