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Credentials

Education ?

Medical School Score
UMDNJ at Stratford (1998)
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Awards & Distinctions ?

Awards  
Patients' Choice Award (2014)
Associations
American Society of Clinical Oncology
Society of Urologic Oncology

Affiliations ?

Dr. Brown is affiliated with 21 hospitals.

Hospital Affiliations

Score

Rankings

  • Kennedy Memorial Hospital -Umc - Stratford
    Urology
    113 E Laurel Rd, Stratford, NJ 08084
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    Top 25%
  • Our Lady Of Lourdes Medical Center
    Urology
    1600 Haddon Ave, Camden, NJ 08103
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    Top 50%
  • Virtua West Jersey Hospital - Voorhees
    94 Brick Rd, Marlton, NJ 08053
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  • Kennedy Memorial Hospital-Umc-Cherry Hill
    Urology
    2201 Chapel Ave W, Cherry Hill, NJ 08002
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  • Virtua West Jersey Hospital - Marlton
    Urology
    94 Brick Rd, Marlton, NJ 08053
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  • Cooper University Hospital
    Urology
    1 Cooper Plz, Camden, NJ 08103
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  • Kennedy University Hospital – Washington Township
    Urology
    435 Hurffville Cross Keys Rd, Blackwood, NJ 08012
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  • Virtua Health-Marlton Division
  • Kennedy Health Systems
    18 E Laurel Rd, Stratford, NJ 08084
  • South Jersey Healthcare - Elmer Hospital
    501 Front St, Elmer, NJ 08318
  • Virtua WJ Hospital Marlton
  • Virtua WJ Hospital Voorhees
  • Virtua Memorial Hospital
  • Virtua Health-Voorhees Division
  • Kennedy Health Systems Washington Township
  • Kennedy Memorial Hospitals - Stratford Division
  • Kennedy Surgical Center
  • Virtua-West Jersey Health System
  • Kennedy Memorial Hospital
  • Kennedy Health Systems Cherry Hill Division
  • Kennedy Memorial Hospitals - Washington Township Division
  • Publications & Research

    Dr. Brown has contributed to 168 publications.
    Title Receptor Heterodimerization: a New Mechanism for Platelet-derived Growth Factor Induced Resistance to Anti-epidermal Growth Factor Receptor Therapy for Bladder Cancer.
    Date February 2011
    Journal The Journal of Urology
    Excerpt

    Human bladder cancer cells resistant to anti-epidermal growth factor receptor therapy often co-express platelet-derived growth factor receptor-β. We determined whether there is functional crosstalk between epidermal growth factor receptor and platelet-derived growth factor receptor-β, and how this regulates biological functions in bladder cancer cases.

    Title Validating Bladder Cancer Xenograft Bioluminescence with Magnetic Resonance Imaging: the Significance of Hypoxia and Necrosis.
    Date January 2011
    Journal Bju International
    Excerpt

    To assess the correlation in orthotopic bladder xenografts of bioluminescence imaging (BLI) with tumour volume as determined by magnetic resonance imaging (MRI), and to define the potential role of hypoxia and necrosis in the relationship between BLI and tumour volume at autopsy.

    Title Incidence of Downstaging and Complete Remission After Neoadjuvant Chemotherapy for High-risk Upper Tract Transitional Cell Carcinoma.
    Date July 2010
    Journal Cancer
    Excerpt

    The authors evaluated the incidence of pathologic downstaging and complete remission (CR) in patients with high-grade ureteral and renal pelvic transitional cell carcinoma (TCC) (upper tract TCC) who received neoadjuvant chemotherapy followed by surgery.

    Title Long-term Outcome for Men with Teratoma Found at Postchemotherapy Retroperitoneal Lymph Node Dissection.
    Date May 2009
    Journal Cancer
    Excerpt

    Patients with pure teratoma within the postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) specimen traditionally have been considered at low risk for disease progression. The objectives of this study were to determine the disease-related outcomes of patients who had pure teratoma identified at the time of PC-RPLND and to examine the prognostic value of clinical variables that were identified previously as important predictors of disease recurrence in these patients.

    Title A Fitness Screening Model for Increasing Fitness Assessment and Research Experiences in Undergraduate Exercise Science Students.
    Date October 2008
    Journal Advances in Physiology Education
    Excerpt

    When students analyze and present original data they have collected, and hence have a cultivated sense of curiosity about the data, student learning is enhanced. It is often difficult to provide students an opportunity to practice their skills, use their knowledge, and gain research experiences during a typical course laboratory. This article describes a model of an out-of-classroom experience during which undergraduate exercise science students provide a free health and fitness screening to the campus community. Although some evidence of the effectiveness of this experience is presented, this is not a detailed evaluation of either the service or learning benefits of the fitness screening. Working in small learning groups in the classroom, students develop hypotheses about the health and fitness of the population to be screened. Then, as part of the health and fitness screening, participants are evaluated for muscular strength, aerobic fitness, body composition, blood pressure, physical activity, and blood cholesterol levels. Students then analyze the data collected during the screening, accept or reject their hypotheses based on statistical analyses of the data, and make in-class presentations of their findings. This learning experience has been used successfully to illustrate the levels of obesity, hypercholesterolemia, and lack of physical fitness in the campus community as well as provide an opportunity for students to use statistical procedures to analyze data. It has also provided students with an opportunity to practice fitness assessment and interpersonal skills that will enhance their future careers.

    Title Is Vascular Endothelial Growth Factor Modulation a Predictor of the Therapeutic Efficacy of Gefitinib for Bladder Cancer?
    Date September 2008
    Journal The Journal of Urology
    Excerpt

    PURPOSE: The epidermal growth factor receptor inhibitor gefitinib (Iressa) is currently being studied in patients with bladder cancer and it has significant anti-angiogenic activity. We investigated the relationship between the modulation of vascular endothelial growth factor (Santa Cruz Biotechnology, Santa Cruz, California) expression and the biological efficacy of gefitinib for bladder cancer. MATERIALS AND METHODS: In vitro the 4 bladder cancer cell lines 253JB-V, UMUC-3, KU-7 and UMUC-13 were treated with gefitinib and vascular endothelial growth factor secretion was measured. The effects of gefitinib on vascular endothelial growth factor promoter, proliferation, cell cycle and downstream signals were evaluated. In vivo 253JB-V and UMUC-13 were injected into nude mice and tumors were treated with 2 mg gefitinib per day. Tumor kinetics were determined and the levels of phospho-epidermal growth factor receptor (Biosource), vascular endothelial growth factor, phospho-vascular endothelial growth factor (Cell Signaling Technology), angiogenesis and apoptosis were measured. RESULTS: Epidermal growth factor receptor (Neomarkers, Fremont, California) phosphorylation was blocked efficiently in all cell lines at concentrations of 0.5 microM or greater. Gefitinib (1 microM) induced an accumulation of cells in G0/G1 without apoptosis in 253J B-V cells, whereas it had no effect in other cell lines. Gefitinib inhibited vascular endothelial growth factor secretion in 253JB-V and UMUC-13 (concentration inhibiting a 50% response 0.5 and 0.1 microM, respectively) but not in UMUC-3 or KU-7. Gefitinib decreased vascular endothelial growth factor promoter activity in 253JB-V and UMUC-13 by 40% to 60%. In vivo the growth of 253JB-V tumors was significantly inhibited by gefitinib, whereas no effect was demonstrated in UMUC-13 tumors. Vascular endothelial growth factor expression and vascular endothelial growth factor receptor activation were significantly decreased in 253JB-V tumors and to a greater extent in resistant UMUC-13 tumors. Gefitinib inhibited angiogenesis and induced apoptosis in sensitive 253JB-V tumors only. CONCLUSIONS: Epidermal growth factor receptor blockade exerts an anti-angiogenic effect on bladder cancer cells, in part by modulating vascular endothelial growth factor expression. However, down-regulation of vascular endothelial growth factor expression is not sufficient to inhibit bladder cancer growth and it should not be used as a predictor of the therapeutic efficacy of gefitinib.

    Title Prostatic Urethral Biopsy Has Limited Usefulness in Counseling Patients Regarding Final Urethral Margin Status During Orthotopic Neobladder Reconstruction.
    Date August 2008
    Journal The Journal of Urology
    Excerpt

    PURPOSE: We determined the value of preoperative transurethral prostatic urethral biopsy in predicting final distal urethral margin status at radical cystectomy. MATERIALS AND METHODS: Of 1,006 patients undergoing radical cystectomy at our institution between 1990 and 2004, 252 were men who underwent ileal neobladder and form the basis of this report. Variables collected include pathology of prostatic urethral biopsies, final pathology of the prostate, frozen section of the distal urethra, final urethral margins and survival data. RESULTS: Median patient age was 61 years. Data regarding preoperative transurethral resection prostatic urethral biopsy and/or frozen section of the urethra at the time of surgery were available for 245 of 252 patients (transurethral resection of the prostatic urethra alone in 127, urethral frozen section alone in 68 and both in 50). The incidence of positive distal urethral margin on final pathological examination was 1.1% (3 of 252) and urethral recurrence was 0.7% (2 of 252). The correlation between transurethral resection findings and frozen section margins was only 68%, and 16 patients with positive transurethral resection findings had negative frozen section margins. The negative predictive value of transurethral resection biopsy with respect to final margins was 99.4% and that of frozen section was 100%. CONCLUSIONS: While patients with no tumor on transurethral resection biopsy of the prostatic urethra have a high likelihood of negative urethral margins on final pathological evaluation, optimal negative predictive value is obtained with frozen sections. Furthermore, a positive transurethral resection prostatic urethral biopsy does not correlate with final margin and should not exclude patients from consideration for orthotopic diversion.

    Title Comparing Lymphadenectomy During Radical Nephroureterectomy: Open Versus Laparoscopic.
    Date May 2008
    Journal Urology
    Excerpt

    OBJECTIVES: Laparoscopic nephroureterectomy (LNU) is an accepted treatment for tumors of the ureter and renal pelvis, although the ability to perform a regional lymphadenectomy has been criticized. We compared the quality of lymphadenectomy with LNU with that involving open nephroureterectomy (ONU) to determine whether oncologic principles are maintained. METHODS: We searched our institutional database for patients who had undergone ONU from 1990 to 2005. These were compared with a series of patients from January 2003 to April 2007 who underwent LNU. From each patient's medical records, we assessed the number of lymph nodes removed, the number of positive nodes removed, and the density of positive nodes. The differences between groups were analyzed using the Wilcoxon rank sum statistical test. RESULTS: We identified 106 patients who underwent ONU with lymphadenectomy and 28 who underwent LNU with lymphadenectomy. The median number of nodes removed, median number of positive nodes, and median density of positive nodes were, respectively, 3, 0, and 0 for the ONU group; and 6, 0, and 0, for the LNU group. There was a statistically significant difference between groups with respect to the number of nodes removed (P = 0.01) but not with respect to the number of positive nodes removed (P = 0.61) or the lymph node density (P = 0.42). CONCLUSIONS: Offsetting the benefits of laparoscopy could be a flawed oncologic technique. We have demonstrated that lymphadenectomy, which is a potentially important component of nephroureterectomy, can be performed as well during LNU as it is with ONU when a dedicated effort is made.

    Title Sensitivity to Epidermal Growth Factor Receptor Inhibitor Requires E-cadherin Expression in Urothelial Carcinoma Cells.
    Date May 2008
    Journal Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
    Excerpt

    PURPOSE: Epidermal growth factor receptor (EGFR) is an attractive target for the treatment of urothelial carcinoma, but a clinical response can be expected in only a small proportion of patients. The aim of this study was to define molecular markers of response to cetuximab therapy in a panel of urothelial carcinoma cell lines. EXPERIMENTAL DESIGN: Eleven cell lines were investigated for antiproliferative response to cetuximab based on [(3)H]thymidine incorporation. A variety of markers, including EGFR expression, phosphorylation, and gene amplification, as well as the expression of other growth factor receptors, their ligands, and markers of epithelial-to-mesenchymal transition were investigated. Cohen's kappa statistic was used to estimate the agreement between response and expression of these markers. E-cadherin was silenced by small interfering RNA in two sensitive cell lines, and the effect on the response to cetuximab was measured. RESULTS: We were able to identify a panel of relevant markers pertaining especially to alternate growth factor receptor expression and epithelial-to-mesenchymal transition that predicted response to cetuximab. The data suggested that expression of intact HER-4 (kappa, 1.00; P = 0.008), E-cadherin (kappa, 0.81; P = 0.015), and beta-catenin (kappa, 0.81; P = 0.015) and loss of expression of platelet-derived growth factor receptor beta (kappa, 0.57; P = 0.167) were associated with response to cetuximab therapy. Silencing E-cadherin in two sensitive cell lines reduced responsiveness to cetuximab in both (P < 0.001). CONCLUSIONS: A panel of predictive markers for cetuximab response has been established in vitro and is currently being evaluated in a prospective clinical trial of neoadjuvant EGFR-targeted therapy. Most importantly, E-cadherin seems to play a central role in modulation of EGFR response in urothelial carcinoma.

    Title Magnetic Resonance Imaging Assessment of a Convective Therapy Delivery Paradigm in a Canine Prostate Model.
    Date March 2008
    Journal Journal of Magnetic Resonance Imaging : Jmri
    Excerpt

    PURPOSE: To quantitatively investigate the feasibility of MRI as a tool for assessing the spatial distribution of a convectively delivered agent using a canine prostate model. MATERIALS AND METHODS: Canine prostates (ex vivo, n = 3; in vivo, n = 12) were injected under several injection paradigms with a solution of gadolinium-DTPA for MR contrast and methylene blue as a grossly visible surrogate drug marker. Ex vivo and in vivo distributions were assessed at 1.5T and quantitatively compared. RESULTS: Measured distributions using MRI and methylene blue pathology photographs were analyzed using a Bland-Altman method. The fractional percentage volume covered (V frac) compared the measurements grossly: Pearson's correlation coefficients were R = 0.99 for ex vivo and R = 0.77 for in vivo (P < 0.05). The fractional percentage of area covered (A frac) demonstrated the high degree of spatial correlation between individual slices: R = 0.93 for ex vivo and R = 0.98 for in vivo (P < 0.05). There was no statistically observable bias in scale or offset between the measurements. CONCLUSION: Measured distributions using MRI and pathology were highly correlated and unbiased, indicating the potential of MRI as a tool for quantitative assessment of interstitial delivery of injected therapies in vivo.

    Title Viable Germ Cell Tumor at Postchemotherapy Retroperitoneal Lymph Node Dissection: Can We Predict Patients at Risk of Disease Progression?
    Date January 2008
    Journal Cancer
    Excerpt

    BACKGROUND: Patients with viable tumor at time of postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) are at an increased risk of disease progression. The objective of the current study was to determine the clinical variables that predict this adverse outcome. METHODS: Between 1980 and 2003, 236 patients with testicular cancer underwent PC-RPLND, 41 of whom (17%) were found to have viable tumor. The authors retrospectively reviewed the patients' medical records for pertinent clinical and treatment-related outcomes. At a median follow-up of 3.9 years, 18 patients (44%) had developed disease recurrence and 12 patients (29%) had died of disease. RESULTS: The group of patients who developed postoperative disease recurrence had a larger median dimension of the retroperitoneal mass (7.0 cm and 3.5 cm, respectively; P = .03). The use of adjuvant chemotherapy after PC-RPLND was less common in those patients developing postoperative disease recurrence (P = .06). On multivariate analysis, patients classified as being at intermediate or poor risk according to the International Germ Cell Consensus Classification (IGCCC) had a poorer recurrence-free survival (P = .006 and P = .07, respectively). On multivariate analysis, predictors of disease-specific survival (DSS) included an elevated alpha-fetoprotein (AFP) level before PC-RPLND (P = .003) and postoperative disease recurrence (P = .02). A serum AFP level >5.3 ng/mL before PC-RPLND was found to be predictive of a poorer DSS (P = .0007). CONCLUSIONS: Patients with viable tumor at the time of PC-RPLND are at an increased risk of disease progression. Clinical variables including classification as intermediate or poor IGCCC risk, a preoperative serum AFP level >5.3 ng/mL, and postoperative disease recurrence help to better define those patients who are at risk of future adverse outcomes.

    Title Lymph Node Density is Superior to Tnm Nodal Status in Predicting Disease-specific Survival After Radical Cystectomy for Bladder Cancer: Analysis of Pooled Data from Mdacc and Mskcc.
    Date January 2008
    Journal Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
    Excerpt

    PURPOSE: To compare the utility of lymph node density (LND) with TNM nodal status in predicting disease-specific survival (DSS) after radical cystectomy. PATIENTS AND METHODS: We identified 248 patients with nodal metastasis after radical cystectomy (without neoadjuvant chemotherapy): 162 patients from Memorial Sloan-Kettering Cancer Center (MSKCC) and 86 patients from M.D. Anderson Cancer Center (MDACC). We assessed the effect of several variables on DSS. RESULTS: After a median follow-up duration of 24 months, 134 patients died of their disease. The median DSS was 36 months, and the 1-year, 2-year, and 5-year DSS rates were 83.7%, 57.4%, and 36.6%, respectively. The median LND was 20%. The 5-year DSS rate was 54.6% for patients with LND < or = 20% v 15.3% for patients with LND higher than 20% (P < .01). Pathologic nodal (pN) status in patients was 78 for pN1 (32%), 127 for pN2 (51%), and 43 for pN3 (17%). On univariate analysis, pN status and LND were significant predictors of DSS (P < .01). However, when pN status and LND were considered jointly in a multivariate model, only LND higher than 20% predicted decreased DSS (hazard ratio [HR], 2.75; P < .01). In addition, while nonorgan-confined (ie, > pT2) primary tumor (HR, 2.40; P < .01) and adjuvant chemotherapy (HR, 0.47; P < .01) were predictors of DSS, LND remained a predictor of DSS even after accounting for adjuvant chemotherapy. CONCLUSION: LND is superior to TNM nodal status in predicting DSS for patients with lymph node-positive disease after radical cystectomy, even in the context of adjuvant chemotherapy.

    Title Distinctive Expression Pattern of Erbb Family Receptors Signifies an Aggressive Variant of Bladder Cancer.
    Date January 2008
    Journal The Journal of Urology
    Excerpt

    PURPOSE: Expression of various members of the ErbB family (epidermal growth factor receptor/ErbB-1, ErbB-2, ErbB-3 and ErbB-4) is associated with disease stage and survival in patients with urothelial carcinoma. We examined the correlation of ErbB family receptor expression with the progression of urothelial carcinoma and survival. MATERIALS AND METHODS: A urothelial carcinoma tissue array was constructed from 248 archival paraffin blocks and quality control studies were ascertained. The tissue microarray was stained for epidermal growth factor receptor, ErbB-2, ErbB-3 and ErbB-4, and analyzed using an automated reader. Patient data included grade, stage, growth pattern, recurrence and survival. RESULTS: Kaplan-Meier estimates of 5-year overall and recurrence-free survival were 58% and 27%, respectively. Patients with high grade, invasive or nonpapillary disease had a worse prognosis than patients with low grade, superficial or papillary disease (p <0.0001). High epidermal growth factor receptor or low ErbB-4 expression was associated with nonpapillary, high grade and invasive tumors as well as with significantly shorter recurrence-free and overall survival (p <0.002, 0.028 and 0.047, respectively). Levels of ErbB-2 and ErbB-3 expression were not associated with overall or recurrence-free survival. CONCLUSIONS: The expression profiles of ErbB-4 and epidermal growth factor receptor are prognostic in urothelial carcinoma. They may help in selecting patients at high risk with bladder cancer for more aggressive therapy.

    Title Recurrence in Nonseminomatous Germ Cell Testis Tumor Patients with No Viable Tumor at Postchemotherapy Retroperitoneal Lymph Node Dissection.
    Date January 2008
    Journal Urology
    Excerpt

    OBJECTIVES: To determine disease-related outcomes in metastatic testis cancer patients with absence of viable cancer in the postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) specimen and determine whether clinical variables can help predict disease progression. METHODS: Between 1980 and 2003, 195 patients had no viable tumor at the time of PC-RPLND. We retrospectively reviewed their medical records for pertinent clinical and treatment-related outcomes. At a median follow-up of 45 months (range, 6 to 236 months), 35 patients (18%) developed recurrences, and 18 (9%) died of disease. RESULTS: On multivariate analysis, predictors of recurrence-free survival in patients with no viable tumor were advanced clinical stage (P = 0.01) and poor-risk International Germ Cell Consensus Classification (IGCCC) group (P = 0.01), whereas predictors of disease-specific survival included an elevated serum beta-human chorionic gonadotropin (hCG) level before PC-RPLND (P = 0.002), pathologic diameter of the retroperitoneal mass (P = 0.05), and postoperative recurrence (P <0.0001). An hCG level greater than 1.2 mIU/mL before PC-RPLND trended toward statistical significance (P = 0.07), and pathologic diameter of the retroperitoneal mass greater than 2.5 cm was statistically significant (P = 0.05) in predicting a poorer disease-specific survival. CONCLUSIONS: Patients with no viable tumor at PC-RPLND remain at risk of recurrence. Several clinical variables, including advanced clinical stage, poor-risk IGCCC group, preoperative serum hCG level, diameter of the retroperitoneal mass on pathology, and postoperative recurrence, help better define which patients are at risk.

    Title Differences in Survival Among Patients with Sarcomatoid Carcinoma, Carcinosarcoma and Urothelial Carcinoma of the Bladder.
    Date January 2008
    Journal The Journal of Urology
    Excerpt

    PURPOSE: Sarcomatoid carcinoma and carcinosarcoma of the bladder are rare tumors that contain epithelial and mesenchymal elements, and may portend a worse prognosis than conventional urothelial carcinoma. We investigated the survival of patients with the 2 tumor subtypes compared to survival in those with urothelial carcinoma. MATERIALS AND METHODS: Cases of sarcomatoid carcinoma, carcinosarcoma and high grade urothelial carcinoma of the bladder were identified from the Surveillance, Epidemiology and End Results Program. Demographic and pathological characteristics were compared. Differences in survival based on histological subtype were estimated using Kaplan-Meier analysis and multivariate Cox proportional hazards regression. RESULTS: Overall unadjusted survival rates for 46,515 patients with urothelial carcinoma, 135 with sarcomatoid carcinoma and 166 with carcinosarcoma were 77%, 54% and 48% at 1 year, and 47%, 37% and 17% at 5 years, respectively. Sarcomatoid carcinoma and carcinosarcoma presented at a similar age but at a higher T stage and with more frequent regional and distant metastases compared to urothelial carcinoma. On multivariate analysis patients with sarcomatoid carcinoma (HR 1.18, 95% CI 0.91-1.52) and carcinosarcoma (HR 2.00, 95% CI 1.65-2.41) were at higher risk for death compared to those with urothelial carcinoma. Overall mortality was worse with carcinosarcoma than with sarcomatoid carcinoma (HR 1.70, 95% CI 1.23-2.34). CONCLUSIONS: Compared to patients with urothelial carcinoma those with sarcomatoid carcinoma and carcinosarcoma present at a more advanced stage and are at greater risk for death even after adjusting for stage at presentation. The survival rate of sarcomatoid carcinoma is better than that of carcinosarcoma, offering some justification for the continued differentiation of these tumor types for clinical prognostication.

    Title An in Vivo Orthotopic Canine Model to Evaluate Distribution of Intraprostatic Injectate: Implications for Gene Therapy and Drug Delivery for Prostate Cancer.
    Date December 2007
    Journal Urology
    Excerpt

    OBJECTIVES: Complete and reliable infiltration of the entire prostate is important to improve the efficacy of intraprostatic gene therapy, as well as drug delivery. We sought to evaluate the optimal injection scheme and feasibility of magnetic resonance imaging (MRI) using a surrogate solution to assess the distribution of injectate in an orthotopic canine model. METHODS: Twelve dogs were anesthetized, and laparotomy was performed. Four dogs in each group were injected with a 1:10 dilution of 1% methylene blue and gadolinium-diethylenetriamine pentaacetic acid using 3, 10, and 20-core injection schemes. The dogs subsequently underwent MRI and then were killed. The prostates were harvested, sectioned, and photographed for methylene blue distribution. The cross-sectional area of the stained pathology and MRI slides was calculated, and correlation studies were performed. Statistical analysis was performed using the paired t test and Pearson's correlation test. RESULTS: The gadolinium distribution reflected the methylene blue distribution, with a Pearson's correlation coefficient of 0.97 (P <0.001). The fractional volume distribution in the 3, 10, and 20-core injection schemes was 10.2%, 28.5%, and 30.1%, respectively. The volume of distribution was significantly greater for the 10-core (P = 0.0024) and 20-core (P = 0.0025) injection schemes than for the 3-core scheme. However, no significant difference was found between the 10 and 20-core schemes (P = 0.52). CONCLUSIONS: MRI using gadolinium-diethylenetriamine pentaacetic acid is an excellent modality to evaluate the effective volume distribution of injectate in an in vivo orthotopic prostate model. The 10-core injection scheme seemed to be as good as the 20-core scheme in achieving adequate distribution of injectate within the prostate.

    Title P0 Stage at Radical Cystectomy for Bladder Cancer is Associated with Improved Outcome Independent of Traditional Clinical Risk Factors.
    Date December 2007
    Journal European Urology
    Excerpt

    OBJECTIVES: Final pathologic specimen free of detectable disease (P0) is not uncommon in patients undergoing cystectomy for bladder cancer, especially in the era of neoadjuvant chemotherapy. To improve our understanding of its significance in a contemporary series, we performed an outcomes analysis of this cohort of patients. METHODS: Over the last 15 yr, 1104 patients with bladder cancer underwent radical cystectomy at our institution. Of these, 120 (11%) were pT0N0M0 (P0) in the surgical specimen and form the basis of this report. Survival data were estimated by method of Kaplan and Meier, with Cox proportional hazards regression model used to evaluate associations between survival and variables studied. RESULTS: Clinical stages were cT1, 21 patients; cT2, 65; cT3b, 20; cT4a, 11; and cT4b, 3. The 5-yr estimates of overall (OS), disease-specific (DSS), and recurrence-free survival (RFS) rates were 84%, 88%, and 84%, respectively. With mean follow-up of 43 mo, 11 patients developed recurrences, 9 of whom died of disease. Median time to recurrence was 7.7 mo (range: 2.2-45 mo). On multivariate analysis, presence of lymphovascular invasion and concomitant carcinoma in situ on the transurethral resection of the bladder tumor specimen were the only significant prognostic factors associated with shorter OS (p = 0.04) and RFS (p = 0.049), respectively. Notably, patients who received preoperative chemotherapy (n = 77) had 5-yr survival rates similar to those of patients who did not. CONCLUSION: Although patients who are P0 at cystectomy have a good prognosis, not all can be considered cured. The favorable prognosis conferred by a P0 state appears to be independent of whether this is achieved by neoadjuvant chemotherapy or by thorough transurethral resection before cystectomy.

    Title Ability of Clinical Grade to Predict Final Pathologic Stage in Upper Urinary Tract Transitional Cell Carcinoma: Implications for Therapy.
    Date October 2007
    Journal Urology
    Excerpt

    OBJECTIVES: To evaluate whether the clinical grade predicts the final pathologic stage in upper urinary tract transitional cell carcinoma. METHODS: We retrospectively reviewed the records of 184 consecutive patients undergoing nephroureterectomy for upper urinary tract transitional cell carcinoma at our institution from 1986 to 2004. Their clinical, surgical, and pathologic data were reviewed to determine the positive and negative predictive values of the clinical biopsy grade with respect to the final pathologic disease stage. RESULTS: Of the 184 patients, 119 (64.7%) had information available regarding the clinical grade of disease from the preoperative endoscopic biopsy. The distribution was grade 1 in 2 (1.6%), grade 2 in 46 (38.7%), and grade 3 in 71 (59.7%) patients. Of the 71 patients with grade 3 disease, 47 had Stage pT2 disease or higher (66% positive predictive value). Of the 48 patients with less than grade 3 disease, 35 had less than pT2 disease (72% negative predictive value). Of the 71 patients with grade 3 disease, 30 had pT3 disease or greater (42% positive predictive value), and of the 48 patients with less than grade 3 disease, 44 had less than pT3 disease (92% negative predictive value). CONCLUSIONS: The histologic grade obtained from the diagnostic biopsy for upper urinary tract transitional cell carcinoma can be used to predict the pathologic disease stage. This information can be used to counsel patients before surgery and to identify patients for whom neoadjuvant chemotherapy would be most beneficial.

    Title Clinical and Therapeutic Significance of Aberrant Differentiation Patterns in Bladder Cancer.
    Date August 2007
    Journal Expert Review of Anticancer Therapy
    Excerpt

    Pure urothelial carcinoma makes up 90-95% of all bladder cancer. The remaining 5-10% represent urothelial carcinoma with aberrant differentiation patterns and nonurothelial carcinoma. Reviews on this topic often focus on the pathological features of these histologic subtypes. In this review we have summarized the clinical significance of each major histologic pattern and analyzed the response of each to standard treatment modalities. The main limitation to optimizing management is the inability to perform clinical trials owing to the rarity of these tumors. This can be circumvented to some degree by extrapolating knowledge acquired from more common similar tumors in other organ sites. Ultimately, however, multicenter clinical trials will need to be organized to address some key management issues.

    Title Design and Validation of 2 Objective Structured Clinical Examination Stations to Assess Core Undergraduate Examination Skills of the Hand and Knee.
    Date July 2007
    Journal The Journal of Rheumatology
    Excerpt

    OBJECTIVE: To evaluate the development, validity, and reliability of 2 undergraduate Objective Structured Clinical Examination (OSCE) stations for core hand and knee examination skills. METHODS: Two OSCE stations for hand and knee based on core skills were developed, and qualitatively assessed for face and content validity by an expert consensus panel. Construct validity was evaluated by comparing the performance of third- (n = 21) and fifth-year (n = 50) medical students with 6 specialist registrars (SpR) in rheumatology. Concurrent validity was evaluated by correlating the scores of the fifth-year students with their eventual final examination scores. The fifth-year data were used to calculate the interrater and intrarater reliabilities of 2 examiners. Intrarater reliability analyzed repeat scores using videotapes of the examinations. RESULTS: Both stations were deemed to fulfil face and content validity criteria by the expert consensus panel. There was no significant difference in the mean scores of the third- and fifth-years. There were significant differences in the mean scores between both student groups and the SpR in both stations consistent with a valid construct theory. The fifth-year hand OSCE results correlated moderately with other indices of clinical skills, but not knowledge, and satisfied concurrent validity. Inter- and intrarater reliability for both stations was high. CONCLUSION: These OSCE stations are valid and reliable tools for testing competency in core hand and knee examination skills. They can be used in educational research as outcome measures of specific teaching interventions and can also be used as an early feedback tool when teaching joint examination.

    Title Pseudosarcomatous and Sarcomatous Proliferations of the Bladder.
    Date May 2007
    Journal Human Pathology
    Excerpt

    Pseudosarcomatous fibromyxoid tumor (PFT), postoperative spindle cell nodule (PSN), sarcoma, and sarcomatoid carcinoma of the bladder are frequently difficult to distinguish histopathologically with significant differences in disease-related outcomes. A retrospective review of our pathology registry over the last 25 years identified 7 PFT, 10 PSN, 18 primary bladder sarcomas, and 17 sarcomatoid carcinomas. Most patients with PFT, PSN, sarcoma, and sarcomatoid carcinoma were diagnosed between the ages of 50 to 60 years with PFT and PSN most commonly detected in women. A previous history of urological instrumentation and bladder cancer was present in all patients with PSN but none of the patients with PFT. Pseudosarcomatous fibromyxoid tumors were characterized by a tissue culture-like proliferation of myofibroblastic cells with focal atypia and overall cytoarchitectural features mimicking nodular fasciitis. Sarcomas and sarcomatoid carcinomas exhibited cellular atypia, mitotic activity with atypical mitosis, and the presence of necrosis. Transurethral resection was sufficient to control all PFT and PSN with no evidence of distant metastatic spread. In contrast, local recurrences and distant metastases frequently occurred in patients with primary sarcoma and sarcomatoid carcinoma despite aggressive surgical management, which was often combined with neoadjuvant chemotherapy (50% and 65% disease-specific mortality, respectively). Pseudosarcomatous fibromyxoid tumor and PSN have unique clinical and pathologic features that allow their distinction from primary bladder sarcoma and sarcomatoid carcinoma.

    Title Surgical Management of Growing Teratoma Syndrome: the M. D. Anderson Cancer Center Experience.
    Date April 2007
    Journal The Journal of Urology
    Excerpt

    PURPOSE: We defined the growth rate and reviewed our experience in the surgical management of growing teratoma syndrome in patients with nonseminomatous germ cell tumors. MATERIALS AND METHODS: Nine patients were clinically diagnosed with growing teratoma syndrome at our center from 1980 to 2003. The defining criteria of growing teratoma syndrome were growing metastatic mass in the retroperitoneum or other site consisting entirely of mature teratoma detected on serial abdominal/pelvic imaging during chemotherapy, and a significant decrease in or normalization of tumor markers. RESULTS: Precise serial abdominal/pelvic radiological measurements of the retroperitoneal masses were available for 7 of 9 patients. The median growth rate of growing teratoma syndrome measured as the increase in diameter during chemotherapy was 0.7 cm per month. The median growth rate measured as the increase in tumor volume was 12.9 cc per month. Median time from the start of chemotherapy to retroperitoneal lymph node dissection was 5.4 months (range 2.7 to 21.6). Pathological evaluation of the retroperitoneal lymph node dissection specimen revealed teratoma with no viable tumor in all 9 cases. There were 2 intraoperative complications (1 aortic and 1 ureteral injury) and 4 postoperative complications (2 ileus, 1 acute pancreatitis and 1 chylous ascites). At a median followup of 2 years 7 patients were alive without disease, 1 died of postoperative sepsis and 1 died of an unknown cause. CONCLUSIONS: The growth rate of growing teratoma syndrome can vary significantly, which must be taken into account when evaluating cases. Retroperitoneal lymph node dissection is an effective treatment for growing teratoma syndrome, providing excellent local control and a low risk of progression.

    Title Laparoscopic Partial Nephrectomy: Experience in 60 Cases.
    Date March 2007
    Journal Journal of Endourology / Endourological Society
    Excerpt

    PURPOSE: To identify the factors associated with better outcomes in patients undergoing laparoscopic partial nephrectomy (LPN). PATIENTS AND METHODS: We retrospectively analyzed the medical records of 36 men and 24 women aged 31 to 80 years (mean 60 years) in whom LPN was attempted at our institution over a 3.5-year period. Baseline patient characteristics and operative, pathologic, and postoperative outcomes were analyzed. The median duration of follow-up was 14.2 months (range 1-38 months). RESULTS: The median pathologic tumor size was 2.1 cm (range 0.7-6.0 cm). Final pathologic review revealed renal-cell carcinoma in 73% of patients. Six patients (10%) required conversion to either an open partial nephrectomy or a laparoscopic radical nephrectomy. Dense perinephric adipose tissue in the setting of a small renal tumor and unanticipated multifocal disease were factors associated with surgical conversion. The median overall estimated blood loss was 112 mL, and the median warm-ischemia time was 30 minutes. Blood loss was greater in patients who did not undergo hilar clamping (467 v 65 mL; P = 0.008). CONCLUSION: Factors influencing successful LPN outcomes include selecting a tumor commensurate with the surgeon's laparoscopic experience, performing routine hilar clamping, adjunctive use of hemostatic agents, and renal-parenchymal suture ligation. The presence of thick, fibrotic perinephric fat overlying a small tumor increases the technical difficulty.

    Title Should Cystectomy Only Be Performed at High-volume Hospitals by High-volume Surgeons?
    Date February 2007
    Journal Current Opinion in Urology
    Excerpt

    PURPOSE OF REVIEW: Monitoring and improving the quality of healthcare is an evolving process that involves patients, physicians, and healthcare purchasers. Growing interest is seen in addressing quality concerns with policy changes. Surgeon and hospital volumes for specific high-risk procedures have been shown to be predictive of posttreatment outcome, but debate continues as to if the evidence justifies changes in practices. We reviewed the literature for robust evidence that surgeon and hospital volumes are markers of improved outcome of radical cystectomy. RECENT FINDINGS: Outcome can be measured by postoperative mortality, as well as complication rate, recurrence rate, and several other factors. Evidence suggests that outcome is improved after cystectomy performed at high-volume centers and by high-volume surgeons. The limitations of volume-based referral policies are discussed, and the use of alternative strategies is reviewed. SUMMARY: A significant regionalization of cystectomy has already been established. Owing to their limitations, however, volume-based referral systems have not been embraced by all parties. New strategies will continue to evolve, and validation of these strategies will be required before clinical implementation.

    Title Nephroureterectomy for Treating Upper Urinary Tract Transitional Cell Carcinoma: Time to Change the Treatment Paradigm?
    Date January 2007
    Journal Bju International
    Excerpt

    OBJECTIVE: To evaluate factors associated with disease recurrence and survival in patients undergoing nephroureterectomy for upper urinary tract transitional cell carcinoma (UUT-TCC) in one centre over an 18-year period. PATIENTS AND METHODS: The records of patients who had a nephroureterectomy for UUT-TCC at our institution from 1986 to 2004 were reviewed for clinical, pathological and treatment period data. Cox's proportional hazards regression model was used to test the statistical significance of several potential prognostic factors for recurrence and survival. RESULTS The median overall duration of follow-up was 2.5 years for 184 patients. Significant prognosticators for disease-specific survival (DSS) by univariate analysis were tumour stage (P < 0.01), tumour grade (P < 0.01), node-positive disease (P < 0.01), multifocality (P = 0.03), previous cystectomy (P < 0.01) and synchronous bilateral UUT-TCC (P = 0.02). On multivariate analysis, only tumour stage (P = 0.03) and grade (P = 0.01) correlated with DSS. The median recurrence-free survival duration was 2.4 years. In 44 patients, the disease recurred outside the bladder; 15 (8.2%) had local recurrence, 20 (10.9%) distant metastasis, and nine (4.9%) both local and distant recurrence. Bladder tumours occurred in 40 (26.1%) patients with no previous cystectomy. The evaluation of treatment outcome during three periods of the study showed no significant effect on DSS. CONCLUSION: Tumour stage and grade correlated with DSS in this cohort, with no improvement in outcome over the 18-year period assessed. Patients with high-stage and high-grade disease continue to fare poorly, suggesting a need for changing the treatment protocol. Judiciously applying a multimodal approach to the management of high-risk patients by incorporating neoadjuvant chemotherapy and surgical resection might provide, for the first time, the opportunity to improve patient outcome.

    Title Recurrence Pattern and Proposed Surveillance Protocol Following Post-chemotherapy Retroperitoneal Lymph Node Dissection.
    Date January 2007
    Journal The Journal of Urology
    Excerpt

    PURPOSE: We evaluated the recurrence pattern in patients with nonseminomatous germ cell tumors treated with post-chemotherapy retroperitoneal lymph node dissection and determined the optimal surveillance strategy in these patients. MATERIALS AND METHODS: Between 1980 and 2003, 236 patients with clinical stage IIA-III nonseminomatous germ cell tumors underwent post-chemotherapy retroperitoneal lymph node dissection. Patients with increased preoperative tumor markers (alpha-fetoprotein greater than 15 ng/ml and/or beta-human chorionic gonadotropin greater than 2.2 U/ml) were excluded from study resulting in 198 patients for analysis. We retrospectively reviewed medical records for pertinent clinical and treatment related outcomes. In our patient population recurrence developed in 45 (23%) patients and 22 (11%) died of disease at a median followup of 41 months (range 6 to 250) after retroperitoneal lymph node dissection. RESULTS: The clinical stage of testis cancer was IIA in 17, IIB in 49, IIC in 83 and III in 49 patients. Of the 45 patients with postoperative recurrence, 16 had concomitant multiple sites of recurrence with a total of 64 sites reported. Of the cases of recurrence 21 (46.7%) were in those of clinical stage III, 18 (40%) stage IIC and 6 (11.8%) stage IIB disease. The most frequent site of recurrence was the chest (32, 49%), followed by the abdomen (14, 22%), supraclavicular lymph nodes (8, 13%), brain (5, 8%) and other sites (5, 8%). CONCLUSIONS: Based on the recurrence pattern we propose stage specific surveillance guidelines for the followup of patients after post-chemotherapy retroperitoneal lymph node dissection. These guidelines help identify patients at high risk for disease progression and, thus, requiring more stringent postoperative followup.

    Title Neoadjuvant Chemotherapy for Bladder Cancer.
    Date January 2007
    Journal World Journal of Urology
    Excerpt

    The 30-45% failure rate after radical cystoprostatectomy mandates that we explore and optimize multimodal therapy to achieve better disease control in these patients. Cisplatin-based multi-agent combination chemotherapy has been used with success in metastatic disease and has therefore also been introduced in patients with high-risk but non-metastatic bladder cancer. There is now convincing evidence that chemotherapy given pre-operatively can improve survival in these patients. In this review we establish the need for peri-operative chemotherapy in bladder cancer patients and summarize the evidence for the efficacy of neoadjuvant chemotherapy. The advantages and disadvantages of neoadjuvant versus adjuvant chemotherapy are discussed, and the main shortcomings of both--treatment-related toxicity and the inability to prospectively identify likely responders--are presented. Finally, a risk-adapted approach to neoadjuvant chemotherapy is presented, whereby the highest risk patients are offered treatment while those unlikely to benefit are spared the treatment-related toxicity.

    Title Molecular Markers of Urothelial Cancer and Their Use in the Monitoring of Superficial Urothelial Cancer.
    Date January 2007
    Journal Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
    Excerpt

    Multiple molecular markers have been described for use in bladder cancer patients. Some of these have been studied more extensively than others, and it is difficult for the clinician to maintain a perspective over the myriad findings that have been made. We have reviewed a selection of markers used for surveillance with an emphasis on clinical utility. The best studied markers and those with the most promising preliminary results were selected. Only studies that included surveillance for recurrence in patients with a history of bladder cancer were considered. Each marker is briefly described and its performance in monitoring bladder cancer patients is summarized. Several promising markers are available, although only four have obtained US Food and Drug Administration approval. The clinical applications that have been studied include replacement or reduction in the number of cystoscopies performed in the surveillance of bladder cancer patients, substitution for or complementary use with urinary cytology in the same setting, predicting disease recurrence and progression, and predicting and monitoring treatment response. None of the markers have been proved sensitive and specific enough to replace cystoscopy. Others, such as nuclear matrix protein 22 (NMP22) and UroVysion, appear to have some utility when used to complement or replace cytology. The other applications have not been adequately studied for any given marker. While multiple molecular markers exist for bladder cancer, their full clinical utility will not be realized until more multicenter prospective trials are conducted to verify their efficacy and safety in the monitoring of patients with superficial bladder cancer.

    Title Testosterone Prohormone Supplements.
    Date December 2006
    Journal Medicine and Science in Sports and Exercise
    Excerpt

    Testosterone prohormones such as androstenedione, androstenediol, and dehydroepiandrosterone (DHEA) have been heavily marketed as testosterone-enhancing and muscle-building nutritional supplements for the past decade. Concerns over the safety of prohormone supplement use prompted the United States Food and Drug Administration to call for a ban on androstenedione sales, and Congress passed the Anabolic Steroid Control Act of 2004, which classifies androstenedione and 17 other steroids as controlled substances. As of January 2005, these substances cannot be sold without prescription. Here, we summarize the current scientific knowledge regarding the efficacy and safety of prohormone supplementation in humans. We focus primarily on androstenedione, but we also discuss DHEA, androstenediol, 19-nor androstenedione, and 19-nor androstenediol supplements. Contrary to marketing claims, research to date indicates that the use of prohormone nutritional supplements (DHEA, androstenedione, androstenediol, and other steroid hormone supplements) does not produce either anabolic or ergogenic effects in men. Moreover, the use of prohormone nutritional supplements may raise the risk for negative health consequences.

    Title Undergraduate Musculoskeletal Examination Teaching by Trained Patient Educators--a Comparison with Doctor-led Teaching.
    Date December 2006
    Journal Rheumatology (oxford, England)
    Excerpt

    BACKGROUND: To compare the core hand and knee examination skills gained by undergraduates taught either by trained patient educators (PEs) or by doctors. METHODS: A total of 50 final year medical students were randomized to receive training from PEs or doctors. Group A were taught hand examination by a PE with rheumatoid arthritis, and knee examination by a PE with osteoarthritis. Group B was taught hand and knee examination by a consultant rheumatologist plus an untrained patient with appropriate signs. All students were taught an established core skills set in small group workshops. Students then undertook two validated objective structured clinical examination (OSCE) stations with two blinded assessors. Pre- and post-teaching questionnaires established the students' self-reported levels of skills (SRS) and a student evaluation of teaching (SET). The study was analysed as an equivalence trial. A mean difference in OSCE scores of 10% was assumed to be of educational significance. RESULTS: Although the SET scores of both groups were high, the doctor-led group received higher scores. Aside from this, the two student groups did not differ significantly. There were no significant differences in mean hand OSCE (mean difference = 0.88, P = 0.28, 95% CI = -0.73 to 2.49) or knee OSCE (mean difference = 0.28, P = 0.7, 95% CI = -1.19 to 1.75) scores. Both the upper and lower confidence intervals for each mean difference fell within the 10% range (-2.8 to 2.8 for the hand, and -2.5 to 2.5 for the knee) and equivalence was assumed. CONCLUSIONS: Adequately trained PEs can deliver clearly structured undergraduate skills, teaching with equivalent learning outcomes to those of rheumatology consultants. PEs are a valuable development to augment musculoskeletal education in the face of expanding student numbers.

    Title Viable Malignant Germ Cell Tumor in the Postchemotherapy Retroperitoneal Lymph Node Dissection Specimen: Can It Be Predicted Using Clinical Parameters?
    Date November 2006
    Journal Cancer
    Excerpt

    BACKGROUND: The presence of viable tumor in the surgical specimen after postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) is associated with an increased risk of disease progression. The objective of this study was to determine whether the presence of viable tumor in the surgical specimen could be predicted. METHODS: Between 1980 and 2003, 236 patients underwent PC-RPLND for clinical Stage IIA or III nonseminomatous germ cell tumors (NSGCT). The authors retrospectively reviewed the medical records of those patients for pertinent clinical and treatment-related outcomes. A multivariate logistic regression analysis was used to evaluate whether clinical parameters were capable of predicting the presence of viable tumor in the surgical specimen. RESULTS: International Germ Cell Consensus Classification (IGCCC) risk categories could be assigned to 218 patients, with 101 patients in the good-risk category, 32 patients in the intermediate-risk category, and 85 patients in the poor-risk category. The incidence of viable tumor in the good-risk, intermediate-risk, and poor-risk categories was similar (17.8%, 15.6%, and 15.3%, respectively); however, the risk categories predicted disease-specific and recurrence-free survival (P = .022 and P < .0001, respectively). On multivariate analysis, an elevated serum alpha-fetoprotein (AFP) level prior to PC-RPLND (P = .05) and the size of the retroperitoneal mass on pathology review (P = .02) were predictive of viable tumor in the surgical specimen. CONCLUSIONS: Although IGCCC risk categories were correlated with disease-related outcomes, the risk groups had similar incidences of viable tumor. Elevated serum AFP levels prior to surgery and the size of the retroperitoneal mass in the resected specimen may help to predict viable tumor in the PC-RPLND specimen.

    Title Predictors of Outcome in Patients Undergoing Postchemotherapy Retroperitoneal Lymph Node Dissection for Testicular Cancer.
    Date November 2006
    Journal Cancer
    Excerpt

    BACKGROUND: The management of metastatic nonseminomatous germ cell tumors (NSGCT) frequently consists of systemic chemotherapy followed by retroperitoneal lymph node dissection (PC-RPLND). The aim of the present study was to evaluate the authors' PC-RPLND experience and identify predictors of outcome in these patients. METHODS: Between 1980 and 2003, 236 patients with clinical Stage IIA-III NSGCT underwent PC-RPLND. Their medical records were retrospectively reviewed for pertinent clinical and treatment-related outcomes. The 5-year disease-specific and recurrence-free survival was 85% and 75%, respectively, with the median length of follow-up after RPLND 45 months (6-250 months). RESULTS: The median age of patients at diagnosis was 28 years, with all patients receiving systemic chemotherapy (median of 5 cycles) before RPLND. On multivariate analysis, predictors of poorer disease-specific survival (DSS) included systemic symptoms at presentation (P = .05), elevated pre-RPLND serum alpha fetoprotein (AFP, P = .006) and beta-human chorionic gonadotropin (HCG, P = .004), postoperative complications (P = .03), and recurrence (P < .0001). Predictors of poorer recurrence-free survival (RFS) included advanced clinical stage (IIC-III, P = .001) and presence of viable tumor in the RPLND specimen (P = .03). A pre-RPLND serum AFP > 9 ng/mL and HCG > 4.1 mIU/mL were found to predict a worse DSS (P = .03 and .03, respectively). CONCLUSIONS: In patients undergoing PC-RPLND, preoperative tumor markers and the occurrence of postoperative complications or recurrence are predictive of poorer DSS. Advanced clinical stage and viable tumor in the surgical specimen predict worse RFS.

    Title Acute Resistance Exercise Does Not Change the Hormonal Response to Sublingual Androstenediol Intake.
    Date September 2006
    Journal European Journal of Applied Physiology
    Excerpt

    Sublingual intake of 21.4 mg androstenediol increases serum testosterone concentrations whereas swallowing 200 mg androstenediol does not. The duration of increase in serum testosterone following sublingual androstenediol (SL-DIOL) is unknown. Resistance exercise (EX) following SL-DIOL may cause larger increases in serum estradiol concentrations than while at rest. This project evaluated the duration of change in, and the effects of acute EX on, the hormonal response to SL-DIOL. Six young resistance trained males consumed either placebo (PL) or SL-DIOL before a single session of EX or no exercise (Rest) in a random, double blind, crossover manner (for a total of four trials). Blood samples were collected before supplementation, and at 60, 120, 180, 240, 480, and 720 min post-supplementation, with the exercise occurring between 60 and 120 min. The serum [total testosterone] increased (P < 0.05) at 60 min similarly in SL-DIOL-EX and SL-DIOL-Rest by approximately 115%, and at 120 min by approximately 107% with no differences due to exercise. The serum [estradiol] increased (P < 0.05) similarly in SL-DIOL-EX and SL-DIOL-Rest by approximately 33% at 60 min and approximately 45% at 120 min, with no differences due to exercise. Serum [testosterone] returned to baseline by 240 min and serum [estradiol] returned to baseline by 720 min post-intake. These findings indicate that SL-DIOL acutely elevates serum testosterone and estradiol concentrations, that EX does not alter the endocrine response to SL-DIOL, and that the increases in serum estradiol last between 480 and 720 min while the increases in serum testosterone last <240 min following acute SL-DIOL intake.

    Title Teaching Skeletal Muscle Adaptations to Aerobic Exercise Using an American Physiological Society Classic Paper by Dr. Philip Gollnick and Colleagues.
    Date September 2006
    Journal Advances in Physiology Education
    Excerpt

    The use of primary research in the classroom enhances the critical thinking abilities of students. The present article describes a strategy for using the American Physiological Society classic paper "Enzyme activity and fiber composition in skeletal muscle of untrained and trained men" by Dr. Philip D. Gollnick and colleagues to enhance the students' ability to understand research, increase their knowledge of the adaptations to exercise, and learn computer skills in data analysis and presentation. By having students read, study, prepare graphs, and discuss the data from a classic paper, they gain an improved understanding of the factors that influence aerobic exercise ability. This study is especially useful for illuminating the exercise-specific differences in bioenergetic enzymes, muscle fiber type, and fitness characteristics that exist between untrained and trained individuals.

    Title Malignant Fibrous Histiocytoma of the Glans Penis: a Case Report.
    Date July 2006
    Journal Analytical and Quantitative Cytology and Histology / the International Academy of Cytology [and] American Society of Cytology
    Excerpt

    BACKGROUND: Malignant fibrous histiocytoma has been regarded as the most common sarcoma of older adults. However, recent opinion regards pleomorphic malignant fibrous histiocytoma as an undifferentiated high grade pleomorphic sarcoma not otherwise classifiable utilizing current techniques available in surgical pathology. Notwithstanding controversy regarding its nomenclature, malignant fibrous histiocytoma involving the penis is exceedingly rare, with only 4 cases previously described, to our knowledge. CASE: An uncircumcised 73-year-old male presented with a painless, granular, partially necrotic lesion beneath the penile foreskin. There was no history of sexually transmitted disease, constitutional symptoms or dysuria. Examination of penile shaft, testicles, spermatic cord and inguinal lymph nodes were unremarkable. Biopsy revealed a markedly pleomorphic sarcoma. Subsequent, partial penectomy revealed the same lesion with an adjacent area of squamous cell carcinoma in situ. CONCLUSION: Malignant fibrous histiocytoma remains a diagnosis of exclusion. The investigation requires extensive tumor sampling in search of areas of differentiation and a complete battery of immunohistochemical markers. Therapeutically important entities in the differential diagnosis that must be ruled out include other poorly differentiated sarcomas, sarcomatoid squamous cell carcinoma and desmoplastic melanoma.

    Title Bone Marrow-derived Cells Home to and Regenerate Retinal Pigment Epithelium After Injury.
    Date June 2006
    Journal Investigative Ophthalmology & Visual Science
    Excerpt

    PURPOSE: To determine whether hematopoietic stem and progenitor cells (HSCs/HPCs) can home to and regenerate the retinal pigment epithelium (RPE) after induced injury. METHODS: Enriched HSCs/HPCs from green fluorescent protein (gfp) transgenic mice were transplanted into irradiated recipient mice to track bone marrow-derived cells. Physical damage was induced by breaching Bruch's membrane and inducing vascular endothelial growth factor A (VEGFa) expression to promote neovascularization. RPE damage was also induced by sodium iodate injection (40 mg/kg) into wild-type or albino C57Bl/6 mice. Cell morphology, gfp expression, the presence of the Y chromosome, and the presence of melanosomes were used to determine whether the injured RPE was being repaired by the donor bone marrow. RESULTS: Injury to the RPE recruits HSC/HPC-derived cells to incorporate into the RPE layer and differentiate into an RPE phenotype. A portion of the HSCs/HPCs adopt RPE morphology, express melanosomes, and integrate into the RPE without cell fusion. CONCLUSIONS: HSCs/HPCs can migrate to the RPE layer after physical or chemical injury and regenerate a portion of the damaged cell layer.

    Title Upper Urinary Tract Tumors with Nontransitional Histology: a Single-center Experience.
    Date April 2006
    Journal Urology
    Excerpt

    OBJECTIVES: To review our experience with patients with upper urinary tract tumors of nonurothelial origin. Upper urinary tract tumors of nonurothelial origin are uncommon entities. To our knowledge, no series of patients with these neoplasms has been published in the past decade. METHODS: We reviewed the records at the University of Texas M. D. Anderson Cancer Center from 1990 to 2004 to identify patients with primary nonurothelial tumors of the upper urinary tract. We reviewed the patient records to collect data on tumor subtype, treatment, recurrence, and survival. RESULTS: Sixteen patients (1.9% of our database of patients with upper urinary tract tumors) were identified; 12 had squamous cell carcinoma, 2 had adenocarcinoma, 1 had sarcomatoid carcinoma, and 1 had small cell carcinoma. The tumors were located in the renal pelvis in 10 and the ureter in 6. Of the 16 patients, 15 had been treated with nephrectomy or nephrouterectomy and 1 with chemotherapy and radiotherapy. Fifteen of the tumors were pathologic Stage T3 or worse. Ten patients received adjuvant chemotherapy. Of the 16 patients, 9 died (1 of unknown causes), 4 were alive without disease, 2 were alive with disease, and 1 was alive at last follow-up with the disease status unknown. The median follow-up was 30.1 months, the median overall survival time was 11.3 months, and 1-year survival rate was 46%. The median recurrence-free survival time and 1-year recurrence-free survival rate were 5.8 months and 38%, respectively. CONCLUSIONS: Primary nonurothelial carcinomas of the renal pelvis and ureter are rare. Our analysis suggests a poor prognosis for most patients with these pathologic types, probably resulting from the advanced stage at diagnosis and poor responses to systemic therapy.

    Title Misconceptions About the Mechanical Advantages of Intramedullary Devices for Treatment of Proximal Femur Fractures.
    Date March 2006
    Journal Acta Orthopaedica
    Title Urinary Excretion of Steroid Metabolites After Chronic Androstenedione Ingestion.
    Date February 2005
    Journal The Journal of Clinical Endocrinology and Metabolism
    Excerpt

    Urinary steroid excretion after androstenedione intake has been examined after a single dose of 50 mg and single doses of 100 or 300 mg/d for 7 d. We evaluated the effects of 28 d of 100 mg three times a day (t.i.d.) androstenedione intake on urinary steroid excretion. Twenty healthy men, ages 30-39 yr (33.5 +/- 0.6), consumed 100 mg androstenedione t.i.d. or placebo for 28 d. Urine samples were analyzed for testosterone, epitestosterone, androsterone, and etiocholanolone via HPLC/tandem mass spectrometry on d 0 and 28. Androstenedione intake increased (P < 0.05) urinary testosterone 35.1 +/- 10.5 ng/ml vs. 251.6 +/- 87.5 ng/ml, epitestosterone 35.3 +/- 8.8 ng/ml vs. 99.7 +/- 28.7 ng/ml, androsterone 2,102 +/- 383 ng/ml vs. 15,767 +/- 3,358 ng/ml, and etiocholanolone 1,698 +/- 409 ng/ml vs. 11,329 +/- 2,656 ng/ml (means +/- se). Although the testosterone to epitestosterone ratio (T/E) tended to increase with androstenedione intake (1.2 +/- 0.3 vs. 4.0 +/- 1.6; P = 0.12), only one subject had a urinary T/E greater than the current Olympic criteria (>6.0) for a positive drug test. Chronic intake of 100 mg androstenedione t.i.d. increases the urinary excretion of steroid metabolites. Due to inconsistent increases in the T/E ratio, the T/E ratio may not effectively detect androstenedione use.

    Title Cone Cell Survival and Downregulation of Gcap1 Protein in the Retinas of Gc1 Knockout Mice.
    Date November 2004
    Journal Investigative Ophthalmology & Visual Science
    Excerpt

    PURPOSE: To examine the spatial and temporal characteristics of cone cell survival and the expression of guanylate cyclase-activating proteins (GCAPs) in the guanylate cyclase (GC)-1 knockout (KO) mouse retina. METHODS: Immunohistochemical analyses with peanut agglutinin and an antibody specific for cone transducin were used to examine cone cell survival in the GC1 KO retina at 4, 5, 9, 16, and 24 weeks of age. Immunohistochemical and Northern and Western blot analyses were used to examine the expression of GCAP1 and GCAP2 in 4- to 5-week-old mice. RESULTS: The number of cone cells appeared normal throughout the superior and inferior retinal regions in 4- and 5-week-old GC1 KO mice but gradually decreased by 6 months. Cone cell loss was exacerbated in the inferior retinal region, with only 2% to 8% remaining by 6 months of age; however, 40% to 70% of the cone cells survived in the superior region at this age. GCAP1 and GCAP2 protein levels were downregulated in GC1 KO retinas at 4 weeks of age and GCAP1 immunostaining was absent from the photoreceptor outer segments. CONCLUSIONS: The results of this study show that the rate of cone cell loss in the GC1 KO mouse is comparable to that previously described in the GUCY1*B chicken and in humans with Leber congenital amaurosis (LCA)-1. The GCAP expression data, when combined with those of previous electrophysiological studies of the GC1 KO mouse retina, provide evidence that GC1-GCAP1 interactions are essential for cone cell function in mice and that GC2 and GCAP2 activities contribute to the rod cell response in the absence of GC1.

    Title Changes in Serum Testosterone and Estradiol Concentrations Following Acute Androstenedione Ingestion in Young Women.
    Date September 2004
    Journal Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Métabolisme
    Excerpt

    The effect of androstenedione intake on serum hormone concentrations in women is equivocal. Therefore, we examined the hormonal response to androstenedione intake in healthy young (22.1 +/- 0.4 y) women for 4 hours. On day 3 of the follicular phase, subjects ingested placebo, 100, or 300 mg androstenedione in a random, double-blind, cross-over manner. Blood samples were collected before and every 30 min for 240 min after intake. Serum androstenedione concentrations (means +/- SE) increased above basal (6.2 +/- 0.8 nmol/l) from 60-240 min for both 100 mg (22.6 +/- 1.0 nmol/l at 240 min) and 300 mg (28.1 +/- 1.3 nmol/l at 210 min). Androstenedione intake increased serum total testosterone concentrations above basal (1.2 +/- 0.2 nmol/l) from 120-240 min (5.5 +/- 0.9 nmol/l at 210 min) with 100 mg and from 60-240 with 300 mg (10.2 +/- 1.6 nmol/l at 210 min). Androstenedione intake also increased serum estradiol concentrations (basal 191 +/- 24 pmol/l) at 150 min with 100 mg (237 +/- 35 pmol/l) and from 150-240 min with 300 mg (reaching 260 +/- 32 pmol/l at 240 min). These data indicate that, in contrast to men, androstenedione intake in women increases serum testosterone concentrations.

    Title Rapid 3-dimensional Prototyping for Surgical Repair of Maxillofacial Fractures: a Technical Note.
    Date July 2004
    Journal Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons
    Title A Current Review of Medical Therapy for Benign Prostatic Hyperplasia.
    Date April 2004
    Journal The Journal of the American Osteopathic Association
    Excerpt

    Benign prostatic hyperplasia (BPH) is one of the most common diseases of aging men. It is estimated that by age 60 years, greater than 50% of men will have histologically documented evidence of the disease. Therapy for this disease has evolved considerably from its inception. Recent data from long-term population-based studies have shed new light on the treatment of this common problem in aging men. The authors review the current state of diagnosis of BPH and medical therapy for this condition in the primary care setting.

    Title Ingestion of a Dietary Supplement Containing Dehydroepiandrosterone (dhea) and Androstenedione Has Minimal Effect on Immune Function in Middle-aged Men.
    Date April 2004
    Journal Journal of the American College of Nutrition
    Excerpt

    OBJECTIVE: This study investigated the effects of four weeks of intake of a supplement containing dehydroepiandrosterone (DHEA), androstenedione and herbal extracts on immune function in middle-aged men. DESIGN: Subjects consumed either an oral placebo or an oral supplement for four weeks. The supplement contained a total daily dose of 150 mg DHEA, 300 mg androstenedione, 750 mg Tribulus terrestris, 625 mg chrysin, 300 mg indole-3-carbinol and 540 mg saw palmetto. MEASUREMENTS: Peripheral blood mononuclear cells were used to assess phytohemagglutinin(PHA)-induced lymphocyte proliferation and cytokine production. The cytokines measured were interleukin (IL)-2, IL-4, IL-10, IL-1beta, and interferon (IFN)-gamma. Serum free testosterone, androstenedione, estradiol, dihydrotestosterone (DHT) were also measured. RESULTS: The supplement significantly increased serum levels of androstenedione, free testosterone, estradiol and DHT during week 1 to week 4. Supplement intake did not affect LPS or ConA proliferation and had minimal effect on PHA-induced proliferation. LPS-induced production of IL-1beta, and PHA-induced IL-2, IL-4, IL-10, or IFN-gamma production was not altered by the supplement. The addition of the same supplement, DHEA or androstenedione alone to lymphocyte cultures in vitro did not alter lymphocyte proliferation, IL-2, IL-10, or IFN-gamma, but did increase IL-4. In addition, serum HDL-C concentration significantly declined. CONCLUSION: These findings suggest that, although chronic intake of a complex dietary supplement containing DHEA, androstenedione and herbal extracts increases serum androgen levels, it has minimal effect on immune function in middle-aged men.

    Title Rapid Prototyping: the Future of Trauma Surgery?
    Date January 2004
    Journal The Journal of Bone and Joint Surgery. American Volume
    Title The Contribution of Adult Hematopoietic Stem Cells to Retinal Neovascularization.
    Date June 2003
    Journal Advances in Experimental Medicine and Biology
    Title Modes of Failure and Preoperative Evaluation.
    Date February 2003
    Journal The Journal of Bone and Joint Surgery. American Volume
    Title Sequenced Reactions with Samarium(ii) Iodide. Sequential Intramolecular Reformatsky/nucleophilic Acyl Substitution Reactions for the Synthesis of Medium-sized Carbocycles.
    Date December 2002
    Journal The Journal of Organic Chemistry
    Excerpt

    Samarium(II) iodide was used to access eight- and nine-membered carbocycles via a domino reaction comprised of a Reformatsky reaction followed by a nucleophilic acyl substitution reaction. This method represents a general and efficient approach to a variety of highly functionalized, stereodefined carbocycles.

    Title Oocyte Injection in the Mouse.
    Date September 2002
    Journal Methods in Molecular Biology (clifton, N.j.)
    Title Three-dimensional Ct Modeling Versus Traditional Radiology Techniques in Treatment of Acetabular Fractures.
    Date July 2002
    Journal The Iowa Orthopaedic Journal
    Excerpt

    Recently, the authors have used the computer-generated three-dimensional (3-D) CT moving images for preoperative planning and screw/pin insertion in more than 28 cases involving plate and screw fixation of complex acetabular fractures. The authors also used stereolithography (wax or plastic 3-D model of bony anatomy) to develop a computer-generated "clip on" interpositioning template for accurate placement of plate and screws. Application of these new technologies gives the surgeon precise information about the fracture patterns and provides an effective means for preoperative planning and accurate fixation of acetabular fractures. The accuracy of the 3-D virtual presentation of the anatomy is impressive and was substantiated by phantom studies. Postoperation CT revealed no case of screw penetration in the joint. Among other benefits over conventional surgical technique, the computer-assisted surgery provided decreased operative time and morbidity, decreased radiation exposure, and obviated the need for oblique, inlet and outlet roentgen views of the pelvis for preoperative planning. A case report specifically demonstrates preoperative planning for reconstruction of acetabular fracture.

    Title Adult Hematopoietic Stem Cells Provide Functional Hemangioblast Activity During Retinal Neovascularization.
    Date June 2002
    Journal Nature Medicine
    Excerpt

    Adults maintain a reservoir of hematopoietic stem cells that can enter the circulation to reach organs in need of regeneration. We developed a novel model of retinal neovascularization in adult mice to examine the role of hematopoietic stem cells in revascularizing ischemic retinas. Adult mice were durably engrafted with hematopoietic stem cells isolated from transgenic mice expressing green fluorescent protein. We performed serial long-term transplants, to ensure activity arose from self-renewing stem cells, and single hematopoietic stem-cell transplants to show clonality. After durable hematopoietic engraftment was established, retinal ischemia was induced to promote neovascularization. Our results indicate that self-renewing adult hematopoietic stem cells have functional hemangioblast activity, that is, they can clonally differentiate into all hematopoietic cell lineages as well as endothelial cells that revascularize adult retina. We also show that recruitment of endothelial precursors to sites of ischemic injury has a significant role in neovascularization.

    Title Application of Computer-generated Stereolithography and Interpositioning Template in Acetabular Fractures: a Report of Eight Cases.
    Date June 2002
    Journal Journal of Orthopaedic Trauma
    Excerpt

    To determine the effectiveness of stereolithography modeling technologies in the surgical treatment of complex acetabular fractures, five patients with a complex fracture of the acetabulum and three patients with posterior wall fractures were considered in this study. The patients were surgically treated using an interposition template for accurate positioning of the fixation plate and screw trajectories. Intraoperative fluoroscopy confirmed precise plate placement and that all screw trajectories missed the hip joint. Fluoroscopy was only needed for confirmation of fracture reduction and for confirmation of screw location. Application of a life-size stereolithographic model of the pelvis and an interpositioning template along with the computer model of the reversed nonfractured contralateral hemipelvis provides an effective means for preoperative planning and accurate fixation of acetabular fractures. Further studies with this type of preplanning equipment may show a decrease in operative time and morbidity, decrease in radiation exposure, and improvement in accuracy of plate and screw placement.

    Title Effects of Androstenedione-herbal Supplementation on Serum Sex Hormone Concentrations in 30- to 59-year-old Men.
    Date May 2002
    Journal International Journal for Vitamin and Nutrition Research. Internationale Zeitschrift Für Vitamin- Und Ernährungsforschung. Journal International De Vitaminologie Et De Nutrition
    Excerpt

    The effectiveness of a nutritional supplement designed to enhance serum testosterone concentrations and prevent the formation of dihydrotestosterone and estrogens from the ingested androgens was investigated in healthy 30- to 59-year old men. Subjects were randomly assigned to consume DION (300 mg androstenedione, 150 mg dehydroepiandrosterone, 540 mg saw palmetto, 300 mg indole-3-carbinol, 625 mg chrysin, and 750 mg Tribulus terrestris per day; n = 28) or placebo (n = 27) for 28 days. Serum free testosterone, total testosterone, androstenedione, dihydrotestosterone, estradiol, prostate-specific antigen (PSA), and lipid concentrations were measured before and throughout the 4-week supplementation period. Serum concentrations of total testosterone and PSA were unchanged by supplementation. DION increased (p < 0.05) serum androstenedione (342%), free testosterone (38%), dihydrotestosterone (71%), and estradiol (103%) concentrations. Serum HDL-C concentrations were reduced by 5.0 mg/dL in DION (p < 0.05). Increases in serum free testosterone (r2 = 0.01), androstenedione (r2 = 0.01), dihydrotestosterone (r2 = 0.03), or estradiol (r2 = 0.07) concentrations in DION were not related to age. While the ingestion of androstenedione combined with herbal products increased serum free testosterone concentrations in older men, these herbal products did not prevent the conversion of ingested androstenedione to estradiol and dihydrotestosterone.

    Title Acute Hormonal Response to Sublingual Androstenediol Intake in Young Men.
    Date April 2002
    Journal Journal of Applied Physiology (bethesda, Md. : 1985)
    Excerpt

    The effectiveness of orally ingested androstenediol in raising serum testosterone concentrations may be limited because of hepatic breakdown of the ingested androgens. Because androstenediol administered sublingually with cyclodextrin bypasses first-pass hepatic catabolism, we evaluated the acute hormonal response to sublingual cyclodextrin androstenediol supplement in young men. Eight men (22.9 +/- 1.2 yr) experienced in strength training consumed either 20 mg androstenediol in a sublingual cyclodextrin tablet (Sl Diol) or placebo (Pl) separated by at least 1 wk in a randomized, double-blind, crossover manner. Blood samples were collected before supplementation and at 30-min intervals for 3 h after supplementation. Serum hormone concentrations did not change with Pl. Serum androstenedione concentrations were increased (P < 0.05) above baseline (11.2 +/- 1.1 nmol/l) with Sl Diol from 60 to 180 min after intake and reached a peak concentration of 25.2 +/- 2.9 nmol/l at 120 min. Serum free testosterone concentrations were increased from 86.2 +/- 9.1 pmol/l with Sl Diol from 30 to 180 min and reached a peak concentration of 175.4 +/- 12.2 pmol/l at 60 min. Serum total testosterone concentrations increased above basal (25.6 +/- 2.3 nmol/l) from 30 to 180 min with Sl Diol and reached a peak concentration of 47.9 + 2.9 nmol/l at 60 min. Serum estradiol concentrations were elevated (P < 0.05) above baseline (0.08 +/- 0.01 nmol/l) from 30 to 180 min with Sl Diol and reached 0.14 +/- 0.02 nmol/l at 180 min. These data indicate that sublingual cyclodextrin androstenediol intake increases serum androstenedione, free testosterone, total testosterone, and estradiol concentrations.

    Title Endocrine and Lipid Responses to Chronic Androstenediol-herbal Supplementation in 30 to 58 Year Old Men.
    Date February 2002
    Journal Journal of the American College of Nutrition
    Excerpt

    OBJECTIVE: The effectiveness of an androgenic nutritional supplement designed to enhance serum testosterone concentrations and prevent the formation of dihydrotestosterone and estrogen was investigated in healthy 3 to 58 year old men. DESIGN: Subjects were randomly assigned to consume a nutritional supplement (AND-HB) containing 300-mg androstenediol, 480-mg saw palmetto, 450-mg indole-3-carbinol, 300-mg chrysin, 1,500 mg gamma-linolenic acid and 1.350-mg Tribulus terrestris per day (n = 28), or placebo (n = 27) for 28 days. Subjects were stratified into age groups to represent the fourth (30 year olds, n = 20), fifth (40 year olds, n = 20) and sixth (50 year olds, n = 16) decades of life. MEASUREMENTS: Serum free testosterone, total testosterone, androstenedione, dihydrotestosterone, estradiol, prostate specific antigen and lipid concentrations were measured before supplementation and weekly for four weeks. RESULTS: Basal serum total testosterone, estradiol, and prostate specific antigen (PSA) concentrations were not different between age groups. Basal serum free testosterone concentrations were higher (p < 0.05) in the 30- (70.5 +/- 3.6 pmol/L) than in the 50 year olds (50.8 +/- 4.5 pmol/L). Basal serum androstenedione and dihydrotestosterone (DHT) concentrations were significantly higher in the 30- (for androstenedione and DHT, respectively, 10.4 +/- 0.6 nmol/L and 2198.2 +/- 166.5 pmol/L) than in the 40- (6.8 +/- 0.5 nmol/L and 1736.8 +/- 152.0 pmol/L) or 50 year olds (6.0 +/- 0.7 nmol/L and 1983.7 +/- 147.8 pmol/L). Basal serum hormone concentrations did not differ between the treatment groups. Serum concentrations of total testosterone and PSA were unchanged by supplementation. Ingestion of AND-HB resulted in increased (p < 0.05) serum androstenedione (174%), free testosterone (37%), DHT (57%) and estradiol (86%) throughout the four weeks. There was no relationship between the increases in serum free testosterone, androstenedione, DHT, or estradiol and age (r2 = 0.08, 0.03, 0.05 and 0.02, respectively). Serum HDL-C concentrations were reduced (p < 0.05) by 0.14 mmol/L in AND-HB. CONCLUSIONS: These data indicate that ingestion of androstenediol combined with herbal products does not prevent the formation of estradiol and dihydrotestosterone.

    Title Scope of the Osce.
    Date December 2001
    Journal British Dental Journal
    Title Potential of Increased Risk of Neurovascular Injury Using Proximal Interlocking Screws of Retrograde Femoral Nails in Patients with Acetabular Fractures.
    Date October 2001
    Journal Journal of Orthopaedic Trauma
    Excerpt

    OBJECTIVES: Neurologic and vascular structures are at risk of iatrogenic injury from proximal interlocking screw insertion after retrograde nailing. This risk may increase in the presence of acetabular fractures because of the displacement of soft tissues resulting from hematoma. The purpose of this study was to establish and compare the relative safe zones (RSZs) for interlocking screw insertion in adults with and without concomitant acetabular fractures. MATERIALS AND METHODS: Thirty pelvic computed tomography scans of patients with acute unilateral acetabular fracture and magnetic resonance imaging scans of five healthy legs were used to evaluate the course of the femoral sheath, neurovascular complex, and the sciatic nerve as they course through the proximal thigh in sixty-five limbs. RESULTS: The anatomy of the neurovascular structures on the fractured side was statistically different from that of the normal side. On the normal side, the RSZ at the lesser trochanteric level was identified from +7 degrees medial to +20 degrees lateral to the sagittal axis (27-degree angle zone) for anteroposterior screw placement. These values for the fractured side, respectively, changed to +1 degrees and +14 degrees (13-degree angle zone), a 52 percent decrease. The RSZ for lateral-medial screw placement was 28 degrees anterior to 39 degrees posterior to the coronal axis (67-degree angle zone) for the normal side, which changed, respectively, to 32 degrees and 41 degrees (73-degree angle zone) for the fractured side. At the level of the lesser trochanter, rotation in the femoral shaft was mimicked only in part (approximately 50 percent) by the neurovascular structures. CONCLUSION: Lateral-medial screw insertion is safer than anteroposterior insertion. Anteroposterior screw insertion becomes even more critical if the acetabulum is fractured. Femoral external rotation after rod insertion, but before screw insertion, will enlarge the safe zones.

    Title Sequenced Reactions with Samarium(ii) Iodide. Sequential Intramolecular Barbier Cyclization/grob Fragmentation for the Synthesis of Medium-sized Carbocycles.
    Date August 2001
    Journal The Journal of Organic Chemistry
    Excerpt

    Samarium(II) iodide was used to access eight-, nine-, and ten-membered carbocycles via a domino reaction composed of a cyclization/fragmentation process. 2-(Iodoalkyl)-, 2-(iodomethyl)allyl-, and 2-(2-iodomethyl)benzyl-2-methyl-3-(methanesulfonyloxy)cycloalkanones were subjected to Barbier-type reductive coupling conditions. Intermediate cycloalkanedione derivatives were also treated under similar conditions, providing bicyclic hydroxy ketones with complete diastereoselectivity and high yields. This method represents a general and efficient approach to a variety of highly functionalized, stereodefined carbocycles.

    Title Endocrine Responses to Chronic Androstenedione Intake in 30- to 56-year-old Men.
    Date December 2000
    Journal The Journal of Clinical Endocrinology and Metabolism
    Excerpt

    In young men, chronic ingestion of 100 mg androstenedione (ASD), three times per day, does not increase serum total testosterone but does increase serum estrogen and ASD concentrations. We investigated the effects of ASD ingestion in healthy 30- to 56-yr-old men. In a double-blind, randomly assigned manner, subjects consumed 100 mg ASD three times daily (n = 28), or placebo (n = 27) for 28 days. Serum ASD, dihydrotestosterone (DHT), free and total testosterone, estradiol, prostate-specific antigen (PSA), and lipid concentrations were measured at week 0 and each week throughout the supplementation period. Serum total testosterone and PSA concentrations did not change with supplementation. Elevated serum concentrations of ASD (300%), free testosterone (45%), DHT (83%), and estradiol (68%) were observed during weeks 1-4 in ASD (P < 0.05). There was no relationship between age and changes in serum ASD (r2 = 0.024), free testosterone (r2 = 0.00), or estradiol (r2 = 0.029) concentrations with ASD, whereas the serum DHT response to ASD ingestion was related to age (r2 = 0.244; P < 0.05). Serum concentrations of high-density lipoprotein cholesterol were decreased by 10% during the supplementation period (P < 0.05). These results suggest that the ingestion of 100 mg ASD, three times per day, does not increase serum total testosterone or PSA concentrations but does elicit increases in ASD, free testosterone, estradiol, and DHT and decreases serum high-density lipoprotein cholesterol concentrations.

    Title Effects of Anabolic Precursors on Serum Testosterone Concentrations and Adaptations to Resistance Training in Young Men.
    Date November 2000
    Journal International Journal of Sport Nutrition and Exercise Metabolism
    Excerpt

    The effects of androgen precursors, combined with herbal extracts designed to enhance testosterone formation and reduce conversion of androgens to estrogens was studied in young men. Subjects performed 3 days of resistance training per week for 8 weeks. Each day during Weeks 1, 2, 4, 5, 7, and 8, subjects consumed either placebo (PL; n = 10) or a supplement (ANDRO-6; n = 10), which contained daily doses of 300 mg androstenedione, 150 mg DHEA, 750 mg Tribulus terrestris, 625 mg Chrysin, 300 mg Indole-3-carbinol, and 540 mg Saw palmetto. Serum androstenedione concentrations were higher in ANDRO-6 after 2, 5, and 8 weeks (p <.05), while serum concentrations of free and total testosterone were unchanged in both groups. Serum estradiol was elevated at Weeks 2, 5, and 8 in ANDRO-6 (p <.05), and serum estrone was elevated at Weeks 5 and 8 (p <.05). Muscle strength increased (p <.05) similarly from Weeks 0 to 4, and again from Weeks 4 to 8 in both treatment groups. The acute effect of one third of the daily dose of ANDRO-6 and PL was studied in 10 men (23 +/- 4 years). Serum androstenedione concentrations were elevated (p <.05) in ANDRO-6 from 150 to 360 min after ingestion, while serum free or total testosterone concentrations were unchanged. These data provide evidence that the addition of these herbal extracts to androstenedione does not result in increased serum testosterone concentrations, reduce the estrogenic effect of androstenedione, and does not augment the adaptations to resistance training.

    Title Mechanical Performance of Standard and Cannulated 4.0-mm Cancellous Bone Screws.
    Date May 2000
    Journal Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society
    Excerpt

    The mechanical performance of bone screws is determined by their pull-out strength (holding power), compressive force, stripping torque, yield bending moment, ultimate bending moment, and fatigue strength. These parameters are related to the parameters of the screw design, including major thread diameter, minor thread diameter, thread length, pitch, shaft diameter, cannulation diameter, and material properties. The goal of the study was to theoretically predict the static performance of five 4.0-mm, 45-46-mm-long, cancellous, partially threaded standard and cannulated bone screws and compare the predictions with experimental measurements. A secondary goal was to determine if cannulation of the bone screw diminished its mechanical performance. The predicted values for pull-out force, compressive force, and stripping torque were determined by the thread length, major thread diameter, and thread shape factor. The screws with the largest major thread diameter and longest thread length had the greatest pull-out force, compressive strength, and stripping torque. However, when correcting for the thread length, a higher thread shape factor compensated for a smaller major diameter. The coefficient of determination (r2) for the correlation between the predicted and measured pull-out force improved from 0.75 to 0.90 when the theoretical model included the thread shape factor. The yield and ultimate bending moments are a function of the section modulus and material properties of the screw. The Ace solid screw had the greatest section modulus and yield and ultimate bending moments. The experimental data support the theoretical models for predicting the mechanical performance of bone screws. The design of the bone screws can be optimized on the basis of theoretical modeling. The strong correlation between the predicted and measured parameters allows comparison between bone screws without repeated experimental tests. Theoretical and experimental results show that cannulation of the bone screw did not inherently diminish its mechanical performance.

    Title The Lax Shoulder in Females. Issues, Answers, but Many More Questions.
    Date April 2000
    Journal Clinical Orthopaedics and Related Research
    Excerpt

    A review of the existing data on shoulder laxity in females reveals there are insufficient data to confirm the commonly held belief that shoulders in females are more lax than shoulders in males. Laxity is not synonymous with instability. Although females may have increased generalized joint laxity relative to males, generalized joint laxity does not correlate with shoulder laxity. There is conflicting data regarding shoulder laxity and gender. A review of patients with multidirectional instability who were treated operatively showed that 55% of the patients were female (N = 94) and 45% were male (N = 77), but the number or gender of patients who were treated nonoperatively was not reported. Multidirectional instability is reviewed in the context of the lax shoulder in the female. Initial treatment should be nonoperative, emphasizing physical therapy and dynamic stabilization of the shoulder. If nonoperative treatment fails, open or arthroscopic inferior capsular shift stabilization is recommended. Additional basic science and clinical trials are needed to determine whether thermal capsulorrhaphy should be considered in the treatment of patients with multidirectional instability of the shoulder.

    Title Rnx Deficiency Results in Congenital Central Hypoventilation.
    Date April 2000
    Journal Nature Genetics
    Excerpt

    The genes Tlx1 (Hox11), Enx (Hox11L2, Tlx-2) and Rnx (Hox11L2, Tlx-3) constitute a family of orphan homeobox genes. In situ hybridization has revealed considerable overlap in their expression within the nervous system, but Rnx is singularly expressed in the developing dorsal and ventral region of the medulla oblongata. Tlx1-deficient and Enx-deficient mice display phenotypes in tissues where the mutated gene is singularly expressed, resulting in asplenogenesis and hyperganglionic megacolon, respectively. To determine the developmental role of Rnx, we disrupted the locus in mouse embryonic stem (ES) cells. Rnx deficient mice developed to term, but all died within 24 hours after birth from a central respiratory failure. The electromyographic activity of intercostal muscles coupled with the C4 ventral root activity assessed in a medulla-spinal cord preparation revealed a high respiratory rate with short inspiratory duration and frequent apnea. Furthermore, a coordinate pattern existed between the abnormal activity of inspiratory neurons in the ventrolateral medulla and C4 motorneuron output, indicating a central respiratory defect in Rnx mice. Thus, Rnx is critical for the development of the ventral medullary respiratory centre and its deficiency results in a syndrome resembling congenital central hypoventilation.

    Title A Descriptive System for Lower Extremity Evaluation in Children: Data for the Newborn Infant.
    Date March 2000
    Journal Orthopedics
    Excerpt

    An efficient and practical system for examination of the lower extremities in newborn infants and children is presented. Measurements of hip rotation and abduction are performed in a supine position. During examination, the foot is held in passive correction or induced weight-bearing position to compare the tibia, forefoot, and hindfoot alignment. Thirty-six newborn infants were examined randomly to establish standard measurements for newborns. The only statistically significant difference between male and female infants occurred in hip abduction and internal and external rotation of the hips during extension. This method of examination of the lower extremity in newborn infants is useful for routine evaluation in all children.

    Title Computed Tomography Image-guided Surgery in Complex Acetabular Fractures.
    Date February 2000
    Journal Clinical Orthopaedics and Related Research
    Excerpt

    Eleven complex acetabular fractures in 10 patients were treated by open reduction with internal fixation incorporating computed tomography image guided software intraoperatively. Each of the implants placed under image guidance was found to be accurate and without penetration of the pelvis or joint space. The setup time for the system was minimal. Accuracy in the range of 1 mm was found when registration was precise (eight cases) and was in the range of 3.5 mm when registration was only approximate (three cases). Added benefits included reduced intraoperative fluoroscopic time, less need for more extensive dissection, and obviation of additional surgical approaches in some cases. Compared with a series of similar fractures treated before this image guided series, the reduction in operative time was significant. For patients with complex anterior and posterior combined fractures, the average operation times with and without application of three-dimensional imaging technique were, respectively, 5 hours 15 minutes and 6 hours 14 minutes, revealing 16% less operative time for those who had surgery using image guidance. In the single column fracture group, the operation time for those with three-dimensional imaging application, was 2 hours 58 minutes and for those with traditional surgery, 3 hours 42 minutes, indicating 20% less operative time for those with imaging modality. Intraoperative computed tomography guided imagery was found to be an accurate and suitable method for use in the operative treatment of complex acetabular fractures with substantial displacement.

    Title Effect of Oral Dhea on Serum Testosterone and Adaptations to Resistance Training in Young Men.
    Date February 2000
    Journal Journal of Applied Physiology (bethesda, Md. : 1985)
    Excerpt

    This study examined the effects of acute dehydroepiandrosterone (DHEA) ingestion on serum steroid hormones and the effect of chronic DHEA intake on the adaptations to resistance training. In 10 young men (23 +/- 4 yr old), ingestion of 50 mg of DHEA increased serum androstenedione concentrations 150% within 60 min (P < 0.05) but did not affect serum testosterone and estrogen concentrations. An additional 19 men (23 +/- 1 yr old) participated in an 8-wk whole body resistance-training program and ingested DHEA (150 mg/day, n = 9) or placebo (n = 10) during weeks 1, 2, 4, 5, 7, and 8. Serum androstenedione concentrations were significantly (P < 0.05) increased in the DHEA-treated group after 2 and 5 wk. Serum concentrations of free and total testosterone, estrone, estradiol, estriol, lipids, and liver transaminases were unaffected by supplementation and training, while strength and lean body mass increased significantly and similarly (P < 0.05) in the men treated with placebo and DHEA. These results suggest that DHEA ingestion does not enhance serum testosterone concentrations or adaptations associated with resistance training in young men.

    Title Improving Student Learning in Root Canal Treatment Using Self-assessment.
    Date November 1999
    Journal International Endodontic Journal
    Excerpt

    AIM: This paper reports the first attempts to implement a new course in endodontology for undergraduate dental students based upon independent, reflective learning and self-assessment. METHODOLOGY: The responses were analysed of two successive cohorts of third-year students to laboratory courses in (i) the restoration of teeth with crowns and (ii) endodontology and root canal treatment. The major changes introduced to the endodontology course were a substantial reduction in the number of formal lectures, the introduction of a series of structured tutorials, time for private study and the use of self-assessment in practical classes. RESULTS: The evidence indicates that the new approach increased student confidence in practical skills, although the time available for operative practice was actually reduced; there was a perceived increase in problem-solving ability; and that students felt encouraged to pursue greater understanding. Reports from tutors suggested that students' self-assessments became more accurate as the courses proceeded. Seven experimental learning points were derived from the study. These included the importance of careful planning, well-designed assessment procedures and the creation of a climate of trust and openness. CONCLUSIONS: The task of developing fully the students' skills of accurate self-assessment remains a challenge.

    Title Comparison Between the Transabdominal and Retroperitoneal Approaches for Aortic Reconstruction in Patients at High Risk.
    Date October 1999
    Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
    Excerpt

    PURPOSE: The purpose of this study was to compare the transabdominal approach with the retroperitoneal approach for elective aortic reconstruction in the patient who is at high risk. METHODS: From January 1992 through January 1997, 148 patients underwent aortic operations: 92 of the patients were classified as American Society of Anesthesia (ASA) class IV. Forty-four operations on the patients of ASA class IV were performed with the transabdominal approach (25 for abdominal aortic aneurysms and 19 for aortoiliac occlusive disease), and 48 operations were performed with the retroperitoneal approach (27 for abdominal aortic aneurysms and 21 for aortoiliac occlusive disease). There were no significant differences between the groups for comorbid risk factors or perioperative care. RESULTS: Among the patients of ASA class IV, eight (8.7%) died after operation (retroperitoneal, 3 [6.26%]; transabdominal, 5 [11.3%]; P =.5). There was no difference between groups in the number of pulmonary complications (retroperitoneal, 23 [47.9%]; transabdominal, 19 [43.2%]; P =.7) or in the development of incisional hernias (retroperitoneal, 6 [12.5%]; transabdominal, 5 [11.3%]; P =.5). The retroperitoneal approach was associated with a significant reduction in cardiac complications (retroperitoneal, 6 [12.5%]; transabdominal, 10 [22.7%]; P =.004) and in gastrointestinal complications (retroperitoneal, 5 [8.3%]; transabdominal, 15 [34.1%]). Operative time was significantly longer in the retroperitoneal group (retroperitoneal, 3.35 hours; transabdominal, 2.98 hours; P =.006), as was blood loss (retroperitoneal, 803 mL; transabdominal, 647 mL; P =.012). The patients in the retroperitoneal group required less intravenous narcotics (retroperitoneal, 36.6 +/- 21 mg; transabdominal, 49.5 +/- 28.5 mg; P =.004) and less epidural analgesics (retroperitoneal, 39.5 +/- 6.4 mg; transabdominal, 56.6 +/- 9.5 mg; P =.004). Hospital length of stay (retroperitoneal, 7.2 +/- 1.6 days; transabdominal, 12.8 +/- 2.3 days; P =.024) and hospital charges (retroperitoneal, $35,587 +/- $980; transabdominal, $54,832 +/- $1105; P =.04) were significantly lower in the retroperitoneal group. The survival rates at the 40-month follow-up period were similar between the groups (retroperitoneal, 81.3%; transabdominal, 78.7%; P =.53). CONCLUSION: In this subset of patients who were at high risk for aortic reconstruction, the postoperative complications were common. However, the number of complications was significantly lower in the retroperitoneal group. Aortic reconstruction in patients of ASA class IV appears to be more safely and economically performed with the retroperitoneal approach.

    Title Effect of Oral Androstenedione on Serum Testosterone and Adaptations to Resistance Training in Young Men: a Randomized Controlled Trial.
    Date June 1999
    Journal Jama : the Journal of the American Medical Association
    Excerpt

    CONTEXT: Androstenedione, a precursor to testosterone, is marketed to increase blood testosterone concentrations as a natural alternative to anabolic steroid use. However, whether androstenedione actually increases blood testosterone levels or produces anabolic androgenic effects is not known. OBJECTIVES: To determine if short- and long-term oral androstenedione supplementation in men increases serum testosterone levels and skeletal muscle fiber size and strength and to examine its effect on blood lipids and markers of liver function. DESIGN AND SETTING: Eight-week randomized controlled trial conducted between February and June 1998. PARTICIPANTS: Thirty healthy, normotestosterogenic men (aged 19-29 years) not taking any nutritional supplements or androgenic-anabolic steroids or engaged in resistance training. INTERVENTIONS: Twenty subjects performed 8 weeks of whole-body resistance training. During weeks 1, 2, 4, 5, 7, and 8, the men were randomized to either androstenedione, 300 mg/d (n = 10), or placebo (n = 10). The effect of a single 100-mg androstenedione dose on serum testosterone and estrogen concentrations was determined in 10 men. MAIN OUTCOME MEASURES: Changes in serum testosterone and estrogen concentrations, muscle strength, muscle fiber cross-sectional area, body composition, blood lipids, and liver transaminase activities based on assessments before and after short- and long-term androstenedione administration. RESULTS: Serum free and total testosterone concentrations were not affected by short- or long-term androstenedione administration. Serum estradiol concentration (mean [SEM]) was higher (P<.05) in the androstenedione group after 2 (310 [20] pmol/L), 5 (300 [30] pmol/L), and 8 (280 [20] pmol/L) weeks compared with presupplementation values (220 [20] pmol/L). The serum estrone concentration was significantly higher (P<.05) after 2 (153 [12] pmol/L) and 5 (142 [15] pmol/L) weeks of androstenedione supplementation compared with baseline (106 [11] pmol/L). Knee extension strength increased significantly (P<.05) and similarly in the placebo (770 [55] N vs 1095 [52] N) and androstenedione (717 [46] N vs 1024 [57] N) groups. The increase of the mean cross-sectional area of type 2 muscle fibers was also similar in androstenedione (4703 [471] vs 5307 [604] mm2; P<.05) and placebo (5271 [485] vs 5728 [451] mm2; P<.05) groups. The significant (P<.05) increases in lean body mass and decreases in fat mass were also not different in the androstenedione and placebo groups. In the androstenedione group, the serum high-density lipoprotein cholesterol concentration was reduced after 2 weeks (1.09 [0.08] mmol/L [42 (3) mg/dL] vs 0.96 [0.08] mmol/L [37 (3) mg/dL]; P<.05) and remained low after 5 and 8 weeks of training and supplementation. CONCLUSIONS: Androstenedione supplementation does not increase serum testosterone concentrations or enhance skeletal muscle adaptations to resistance training in normotestosterogenic young men and may result in adverse health consequences.

    Title Prostatic Adenocarcinoma Diagnosed by Prostate-specific Antigen Analysis of Pleural Fluid.
    Date September 1998
    Journal Urologia Internationalis
    Excerpt

    Adenocarcinoma of the prostate may result in a malignant pleural effusion. However, most of these cases involve patients with either a known primary prostate cancer or radiographic evidence of pulmonary metastases. Occasionally, the initial diagnosis of prostate cancer is made because of prostate-specific antigen (PSA) staining cells in the pleural fluid. We report a case of adenocarcinoma of the prostate that was suspected only because of an elevated PSA in the pleural fluid in a patient who lacked malignant cytology, a history of prostate cancer, and radiographic evidence of pulmonary disease.

    Title Selective Sensitization of Adriamycin-resistant P388 Murine Leukemia Cells to Antineoplastic Agents Following Transfection with Human Dna Topoisomerase Ii Alpha.
    Date March 1998
    Journal Anticancer Research
    Excerpt

    Previous studies have demonstrated decreased levels of DNA topoisomerase II alpha protein and messenger RNA in the Adriamycin-resistant P388 murine leukemia cell line P388/ADR/7 compared to the sensitive P388/4 cell line. An allelic fusion event involving the topoisomerase II alpha and the retinoic acid receptor a genes has been identified in these cells that probably contributes to the decreased topoisomerase II activity in P388/ADR/7 cells. However, this allelic mutation may be a minor contributor or even incidental to the resistance phenotype, since these cells display other candidate mechanisms of resistance, including increased P-glycoprotein, increased glutathione-S-transferase activity and an increased onset of DNA repair. To establish a role for topoisomerase II alpha in mediating the Adriamycin resistance phenotype, complementation of the mutant allele was attempted by transfecting the murine P388/ADR/7 cells with a human topoisomerase II alpha expression construct under the control of the human metallothionein IIA promoter. The majority of transfected cell lines that were obtained by selection in hygromycin B contained copies of the integrated expression construct that were rearranged. Only two of thirty-two transfected cell lines were found to contain a single, unrearranged copy of the human topoisomerase II alpha cDNA. P388/ADR/7 cell lines carrying an integrated, intact human topoisomerase II alpha expression vector were more sensitive to Adriamycin, daunorubicin, mitoxantrone, and etoposide, but not to actinomycin D and vincristine compared to control cells transfected with vector alone or cell lines with rearranged topoisomerase II alpha expression constructs. These findings suggest that topoisomerase II alpha is a selective and significant contributor to multifactorial resistance.

    Title Enx (hox11l1)-deficient Mice Develop Myenteric Neuronal Hyperplasia and Megacolon.
    Date July 1997
    Journal Nature Medicine
    Excerpt

    The isolated homeobox gene Enx (Hox11L1) is expressed in enteric neurons innervating distal ileum, and proximal and distal colon. Enx-deficient mice develop megacolon with massive distension of the proximal colon. The number of myenteric ganglia, total neurons per ganglion, and NADPH diaphorase presumptive inhibitory neurons per ganglion are increased in the proximal and distal colon, but decreased in the distal ileum of all Enx-/- mice. Enx-/- mice provide a model for human neuronal intestinal dysplasia (NID), in which myenteric neuronal hyperplasia and megacolon are seen. These results suggest that Enx is required for the proper positional specification and differentiative cell fate of enteric neurons.

    Title Comparison of Failure Strength Between Metallic and Absorbable Interference Screws. Influence of Insertion Torque, Tunnel-bone Block Gap, Bone Mineral Density, and Interference.
    Date October 1996
    Journal The American Journal of Sports Medicine
    Excerpt

    Because of the good initial fixation strength of interference screws used in anterior cruciate ligament reconstruction, metal interference screws have become the standard method for fixation of bone-patellar tendon-bone grafts. To avoid some of the complications with metal screws, a bioabsorbable interference screw was developed. Data on fixation strength in older human cadavers indicate a similar failure strength between bioabsorbable and metal screws. We studied the failure mechanisms, insertion torques, and fixation strengths of absorbable and metal interference screws in cadaveric knees from young and middle-aged donors. With identical gap and screw size, the mean insertion torque for the metal screws (mean, 1.5 N-m; SD, 0.8) was significantly higher than for the absorbable screws (mean, 0.3 N-m; SD, 0.19). The mean failure load for the metal screws (mean 640 N; SD, 201) was also significantly higher than for the absorbable screws (mean, 418 N; SD, 118).

    Title Fixation Strength of Interference Screw Fixation in Bovine, Young Human, and Elderly Human Cadaver Knees: Influence of Insertion Torque, Tunnel-bone Block Gap, and Interference.
    Date September 1996
    Journal Knee Surgery, Sports Traumatology, Arthroscopy : Official Journal of the Esska
    Excerpt

    A failure analysis of interference screw fixation was performed to test the hypothesis that bovine and/or elderly human cadavers are appropriate models for bone-patellar tendon-bone anterior cruciate ligament (ACL) reconstruction fixation studies. Failure mode is an important criterion for validating experimental models. The bovine, young human, and elderly human failure loads were 799 +/- 261 N, 655 +/- 186 N, and 382 +/- 118 N, respectively, and the failure modes were 75%, 69%, and 30% tissue failures, respectively. The similarities between the bovine and young human models in failure loads and failure modes indicate that bovine models are appropriate for ACL reconstruction fixation studies. The statistically significant differences between the young human and elderly human models in failure loads and failure modes indicate that elderly human cadavers are not an appropriate model for ACL reconstruction fixation studies. The differences in failure modes are consistent with previous studies using elderly human cadavers in which the predominant failure mode was bone block pullout. The tissue failures observed in the bovine and young human models contradict previous studies suggesting fixation strength is the weakest link in bone-patellar tendon-bone ACL reconstruction. Results of linear regression modeling showed statistically significant correlations between insertion torque and failure load (R2 = 0.44, P < 0.0001) and interference (defined as the screw outer thread diameter minus the tunnel-bone block gap) and insertion torque (R2 = 0.18, P = 0.003) when data from all models was combined. Results for the bovine model multiple regression showed a statistically significant regression of insertion torque (linear) and interference (quadritic) versus failure load (R2 = 0.56, P = 0.02). Regression slopes for screw diameter (P = 0.52) and gap size (P = 1.00) were not statistically significant. These results indicate that insertion torque and interference are independent predictors of failure load and should be included in future interference screw studies in addition to bone block dimensions, tunnel size, gap size, and screw diameter. Clinicians may consider using insertion torque and interference as indicators of postoperative graft fixation regarding rehabilitation decisions.

    Title Retinoic Acid-mediated Decrease of G (alpha S) Protein Expression: Involvement of G (alpha S) in the Differentiation of Hl-60 Myeloid Cells.
    Date July 1996
    Journal Experimental Cell Research
    Excerpt

    The amount of the heterotrimeric G protein subunit G (alpha S) decreases after the induction of human myeloblastic leukemia HL-60 cells to become granulocyte-like cells in the presence of retinoic acid (RA). Compared to untreated control cells, HL-60 cells expressed decreased levels of G (alpha S) protein and mRNA levels after addition of RA to the cultures as shown by immunoblot and Northern blot analysis. The reduction of the G (alpha S) protein in HL-60 cells by antisense RNA expression was associated with (i) decreased cell doubling time; (ii) induction of a granulocyte-like phenotype; (iii) and expression of a surface marker characteristic of myeloid differentiation. Expression of a constitutively active mutant G (alpha S) (Q227L) in HL-60 cells blocked RA-induced differentiation. In contrast, treatment with forskolin, prostaglandin E2, or 8-bromo-cyclic AMP, which increase intracellular cyclic AMP (cAMP) levels, did not inhibit the RA-mediated differentiation process. No changes in cAMP levels occurred in response to RA. The present study provides insights into the involvement of G (alpha S) protein in growth regulation during differentiation of the human myeloid cell line HL-60. These data suggest that in HL-60 human myeloid cells RA-mediated decrease of G (alpha S) plays a critical role in the regulation of differentiation which is independent of intracellular cAMP.

    Title Altered Hox Expression and Segmental Identity in Mll-mutant Mice.
    Date December 1995
    Journal Nature
    Excerpt

    The mixed-lineage leukaemia gene (MLL/HRX/ALL-1) is disrupted by chromosomal translocation in human acute leukaemias that often display mixed lymphoid-myeloid phenotypes and present in infancy. MLL possesses a highly conserved SET domain also found in Drosophila trithorax (trx) and Polycomb group (Pc-G) genes, which are known to regulate homeotic genes (HOM-C) in a positive or negative fashion, respectively. Mll was targeted in mice by homologous recombination in embryonic stem (ES) cells to assess its role in pattern development. Mll heterozygous (+/-) mice had retarded growth, displayed haematopoietic abnormalities, and demonstrated bidirectional homeotic transformations of the axial skeleton as well as sternal malformations. Mll deficiency (-/-) was embryonic lethal. Anterior boundaries of Hoxa-7 and Hoxc-9 expression were shifted posteriorly in Mll +/- embryos, but their expression was abolished in Mll -/- embryos. Thus Mll is required for proper segment identity in mammals, displays haplo-insufficiency, and positively regulates Hox gene expression.

    Title Bax-deficient Mice with Lymphoid Hyperplasia and Male Germ Cell Death.
    Date November 1995
    Journal Science (new York, N.y.)
    Excerpt

    BAX, a heterodimeric partner of BCL2, counters BCL2 and promotes apoptosis in gain-of-function experiments. A Bax knockout mouse was generated that proved viable but displayed lineage-specific aberrations in cell death. Thymocytes and B cells in this mouse displayed hyperplasia, and Bax-deficient ovaries contained unusual atretic follicles with excess granulosa cells. In contrast, Bax-deficient males were infertile as a result of disordered seminiferous tubules with an accumulation of atypical premeiotic germ cells, but no mature haploid sperm. Multinucleated giant cells and dysplastic cells accompanied massive cell death. Thus, the loss of Bax results in hyperplasia or hypoplasia, depending on the cellular context.

    Title Regional Lidocaine Anesthesia Without Exsanguination for Outpatient Management of Upper Extremity Fractures.
    Date September 1995
    Journal The Iowa Orthopaedic Journal
    Excerpt

    The use of small dose intravenous lidocaine without exsanguination for upper extremity fractures in children and adults is described. A twenty-plus year experience with this technique in the outpatient setting has shown it to be effective and safe. Attention to detail is essential and inadvertent tourniquet release must be avoided.

    Title Remission Following an Elemental Diet or Prednisolone in Crohn's Disease.
    Date June 1995
    Journal Acta Paediatrica (oslo, Norway : 1992)
    Excerpt

    The short- and long-term effects of an elemental diet in children with acute Crohn's disease were compared with those of prednisolone in historical controls. Clinical remission was induced in 25 of 30 and in 18 of 28 episodes treated for six weeks with an elemental diet and prednisolone. Patients with proximal disease had longer remission after treatment with an elemental diet (p < 0.05) than did patients with colonic disease after treatment with prednisolone (p < 0.01). Disease activity index score improved in both groups compared with the pretreatment scores (p < 0.05). However, the improvement in the elemental diet group was significantly better than in the prednisolone group (p < 0.001). Changes in linear growth were better after treatment with an elemental diet compared with steroids (p < 0.001). Serum albumin and haematocrit concentrations all improved significantly in the children treated with an elemental diet (p < 0.001) but not in those treated with steroids. Thus an elemental diet was better than prednisolone in proximal disease and confirmed improved growth and nutritional status.

    Title Relationship of Dna Topoisomerase Ii Alpha and Beta Expression to Cytotoxicity of Antineoplastic Agents in Human Acute Lymphoblastic Leukemia Cell Lines.
    Date January 1995
    Journal Cancer Research
    Excerpt

    The levels of expression of topoisomerase II alpha and topoisomerase II beta were investigated in six established cell lines of human childhood acute lymphoblastic leukemia (ALL) as a function of doubling time, cell cycle distribution, and of sensitivity to the antineoplastic agents Adriamycin and etoposide. The slowest growing cell line, ALL-G, was most sensitive to both drugs, whereas the fastest growing cell line, ALL-C, was 15.3- and 6.4-fold more resistant than ALL-G to Adriamycin and etoposide, respectively. Furthermore, ALL-W, the second most rapidly dividing cell line, was most resistant to both Adriamycin (22.8-fold) and etoposide (14.1-fold). Expression of topoisomerase II alpha varied inversely with doubling time, whereas no correlation was found between topoisomerase II beta levels and doubling time. Expression of topoisomerase II beta varied inversely with that of topoisomerase II alpha. The level of topoisomerase II alpha correlated directly with the percentage of cells in S and G2-M phases, whereas topoisomerase II beta expression varied directly with the number of cells in G1. An inverse correlation was found between the level of expression of topoisomerase II beta and resistance to Adriamycin, whereas a direct correlation was observed between the level of expression of topoisomerase II alpha and resistance to Adriamycin. Studies with etoposide, although not statistically significant, were consistent with the pattern observed with Adriamycin. These findings suggest that in ALL cells, cytocidal activity of Adriamycin and etoposide may be mediated, at least in part, by topoisomerase II beta.

    Title New Method for Determining Faecal Fat Excretion in Infancy.
    Date July 1994
    Journal Archives of Disease in Childhood
    Excerpt

    Collecting complete, timed stool samples for the estimation of faecal fat from infants wearing nappies is difficult. A gravimetric method has been adapted by applying a chloroform/methanol homophasic solvent system to extract lipids from whole soiled nappies. In a study of 22 collections in six infants, no stools were lost and the recovery of lipids was 96%, with results similar to a reference titrimetric method. In addition to total fat, individual lipids were measured using gas-liquid chromatography. The method simplifies stool collection and analysis, is aesthetically more acceptable, and leads to reduced microbial hazards. It also allows the detailed study of excreted lipid species enabling the coefficient of absorption of dietary lipids of various chain lengths to be determined individually.

    Title Pancreatic Exocrine Function and Necrotising Enterocolitis.
    Date April 1994
    Journal Early Human Development
    Excerpt

    Pancreatic protease deficiency may be an aetiological factor in enteritis necroticans, a disease sharing some features of necrotising enterocolitis (NEC). Using faecal chymotrypsin measurement we have prospectively studied pancreatic exocrine function in infants at risk of NEC. No significant difference was found comparing those infants who subsequently developed NEC and those who did not.

    Title Chondroid Chordoma--a Variant of Chordoma. A Morphologic and Immunohistochemical Study.
    Date February 1994
    Journal American Journal of Clinical Pathology
    Excerpt

    In 1973, Heffelfinger and coworkers described a variant of chordoma that contained cartilaginous areas indistinguishable from hyaline type chondrosarcoma. They designated these tumors chondroid chordomas and found that they had a better prognosis than classic (nonchondroid) chordomas. Since that time, there has been an ongoing debate over whether chondroid chordoma is best considered a distinct clinicopathologic entity separable from chondrosarcoma or a misdiagnosed chondrosarcoma whose concept developed from the erroneous interpretation of morphology. In an attempt to clarify the issue, the authors used light microscopy and immunohistochemistry to study 12 chondroid chordomas, 38 classic chordomas, and 28 chondrosarcomas that arose in the base of the skull or spine. As a reference, they also analyzed the immunohistochemical profile of fetal notochord, ecchordosis physaliphora, and fetal hyaline cartilage. They found that all chondroid and nonchondroid chordomas were positive for cytokeratin, and the majority were also positive for epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA). In contrast, none of the chondrosarcomas stained for cytokeratin, EMA or CEA. Vimentin and S-100 were positive in more than 95% of both classic and chondroid chordomas and chondrosarcomas. The immunohistochemical profile of these tumors was similar to the pattern of immunoreactivity of their nonneoplastic counterparts. The authors conclude that chondroid chordomas is a variant of chordoma and should not be confused with chondrosarcoma. Because chondroid chordomas have been reported to have a better prognosis, they felt that this nosologic term should be preserved and that chondroid chordoma should continue to be a focus of clinical and pathologic study.

    Title Characterization of a Dna Topoisomerase Iialpha Gene Rearrangement in Adriamycin-resistant P388 Leukemia: Expression of a Fusion Messenger Rna Transcript Encoding Topoisomerase Iialpha and the Retinoic Acid Receptor Alpha Locus.
    Date January 1994
    Journal Cancer Research
    Excerpt

    Previous studies using cloned lines of Adriamycin-sensitive and -resistant P388 murine leukemia cells have suggested that a reduction in DNA topoisomerase II alpha (topo II alpha) enzyme activity and protein levels in drug-resistant cell lines (A. M. Deffie, J. K. Batra, and G. J. Goldenberg, Cancer Res., 49: 58-62, 1989) may be due to an allelic mutation in the topo II alpha gene (A. M. Deffie, D. J. Bosman, and G. J. Goldenberg, Cancer Res., 49: 6879-6882, 1989). The drug-resistant cell lines P388/ADR/3 and P388/ADR/7 express a shortened topo II alpha mRNA transcript in addition to the native transcript present in the drug-sensitive P388/4 cell line. Using complementary DNA probes derived from the coding sequence and 3' untranslated region of the native mouse topo II alpha transcript, we have determined that the shorter 4.5-kilobase topo II alpha transcript expressed in the drug-resistant cell lines contains only 3.5-kilobases of topo II sequence from the 5'-terminus onwards. Using a 3'-rapid amplification of cDNA ends strategy, we have cloned cDNAs representing the 3'-termini of both the native and mutant transcripts from both P388/ADR/3 and P388/ADR/7 cells. DNA sequence analysis revealed that the shorter 4.5-kilobase transcript: (a) encodes topoisomerase II alpha until nucleotide position 3494, at which point the sequence diverges for the remaining 956 bases; (b) contains a polyadenylation signal distinct from the native transcript; and (c) contains an open reading frame predicting a truncated topo II alpha fusion protein. Of great interest was the finding that the non-topo II alpha 956-base sequence in the shorter transcript encodes the promoter, exon I, and part of the first intron of the murine retinoic acid receptor alpha gene locus in the antisense orientation, suggesting that a rearrangement on chromosome 11 in the drug-resistant cells led to a gene fusion event between the loci encoding topo II alpha and retinoic acid receptor alpha.

    Title The Pathogenesis of Wild Type and Drug Resistant Mutant Strains of Bovine Herpesvirus-1 (bhv-1) in the Natural Host.
    Date February 1993
    Journal Archives of Virology
    Excerpt

    An experimental infection with bovine herpesvirus-1 was established in calves by means of intranasal inoculation. Three calves were infected with the parental strain BHV-1 w/t, three with the TK-defective strain, B 1 and four with the HPMPA-resistant strain, 3 A. Inoculation with w/t virus resulted in a reproducible clinical disease characterised by respiratory distress, fever and the presence of virus in nasal mucus. Following the acute infection, w/t-inoculated animals became seropositive for BHV-1 specific antibody. The TK-defective mutant (BHV-1 B 1) produced an acute infection similar to the parental virus in all three calves inoculated. The HPMPA-resistant mutant (BHV-1 3 A), however, showed a reduced pattern of infection and virus of lower titre was isolated from three of four calves; the antibody responses were generally lower, and one calf remained seronegative until reactivation. Following stimulation with dexamethasone 72 days after the primary inoculation, virus was re-isolated from all wild type-inoculated calves. In contrast, no evidence of reactivation was obtained from the three B 1-inoculated animals. However, all four animals inoculated with the mutant 3 A showed virus reactivation including the calf which had remained seronegative following primary virus inoculation. Previous studies have suggested that drug-resistance mutations in herpesviruses frequently are associated with reduced pathogenicity on the basis of experiments in laboratory models. The importance of the present study is the demonstration that two different drug-resistant variants of an alpha herpesvirus both have altered pathogenicity in the natural host for that infection. These results also have implications for the design and use of attenuated vaccine strains.

    Title The Steatocrit: an Improved Procedure.
    Date November 1992
    Journal Annals of Clinical Biochemistry
    Excerpt

    The steatocrit is a simple and easily repeated assay for measuring the fat content of infants' stools. However, we and others have experienced technical difficulties in its use. Three modifications were therefore made to the original procedure: incorporation of a lipid-soluble dye, improved homogenization and a heating step. The modified method was used to measure the stool fat content of young children with and without clinical steatorrhoea. Validation of the modified steatocrit is presented, together with examples of its application to both clinical research and clinical practice.

    Title Saline Breast Implant Sloshing and Bubble Hydrostatics.
    Date October 1992
    Journal Plastic and Reconstructive Surgery
    Title The Nature of Small Bowel Luminal Fluid Lactase.
    Date July 1992
    Journal Clinica Chimica Acta; International Journal of Clinical Chemistry
    Excerpt

    The evidence indicating a mucosal source for the jejunal fluid lactase activity of children is so far inconclusive. Samples of jejunal mucosa and the adjacent fluid were obtained simultaneously from 15 children. Lactase activity was measured at pH 5.9 in mucosa and fluid. Fluid activities showed a significant positive correlation with the activity of the corresponding mucosal homogenate but a stronger correlation was found with an enterocyte microvillous membrane fraction prepared from the same homogenate (r = 0.807 and 0.889, respectively). Kinetic and pH optima studies were consistent with a microvillous membrane origin. Fluid activity and pH optimum were not changed detectably when measured in the presence of an enterocyte lysosomal acid lactase inhibitor. Jejunal fluid lactase activity and its properties closely reflect the microvillous membrane enzyme. Lysosomal acid lactase does not contribute measurably to the total lactase activity of jejunal fluid.

    Title Elevated Short Chain Fatty Acid Concentrations in Anaerobic Small Bowel Contamination.
    Date July 1992
    Journal Acta Paediatrica (oslo, Norway : 1992)
    Excerpt

    Viable bacteria were identified and counted, and short chain fatty acid concentrations measured in small intestinal fluid from 74 fasting children. In nine children with anaerobic small bowel contamination, individual and total short chain fatty acid concentrations were significantly higher than the remainder of the group (p less than 0.01). Using 100 mumol/l as the upper reference limit for total short chain fatty acid concentration, the sensitivity and specificity as a test for anaerobic small bowel contamination was 89% and 98%, respectively. Measuring luminal short chain fatty acid concentrations in proximal small intestinal fluid is an accurate method for detecting anaerobic small bowel contamination in children.

    Title Using the Steatocrit to Determine Optimal Fat Content in Modular Feeds.
    Date July 1992
    Journal Archives of Disease in Childhood
    Excerpt

    The steatocrit was measured in infants with protracted diarrhoea who were receiving intragastric modular feeds. Measurements were made when fat intake was constant to determine steatocrit variability and during increases in fat intake to determine fat tolerance limits. Steatocrit variability was expressed as the range between a subject's lowest and highest steatocrit value. The median between-stool and between-day variabilities were 2% and 11% respectively. Variability was also measured in seven healthy breast fed infants. In the five still displaying appreciable physiological steatorrhoea, the between-day variability (median 8%) and between-stool variability (median 9%) were not significantly different from the protracted diarrhoea group. In the fat tolerance investigations in the protracted diarrhoea group, the steatocrit increased with increases in the module fat content. Fat intake and steatocrit were significantly positively related. A significant negative correlation was seen between steatocrit and weight gain, the latter becoming negligible at steatocrit values around 30%.

    Title Completed Follow-up of 1,000 Consecutive Transcervical Chorionic Villus Samplings Performed by a Single Operator.
    Date April 1992
    Journal The Australian & New Zealand Journal of Obstetrics & Gynaecology
    Excerpt

    Completed follow-up data on 1,000 patients undergoing transcervical chorionic villus sampling (CVS) performed by a single operator at the Royal Hospital for Women is presented. Prior to the introduction of CVS, approximately 750 amniocenteses were performed annually in this unit. Over the past 5 years the total number of patients having CVS or amniocentesis has increased by 1/3 and almost 1/2 of procedures are now done by CVS. We have persisted with the transcervical route believing that once the learning curve is past, this route compares favourably with the transabdominal method in loss rate and perinatal outcome. We feel the transcervical approach is better tolerated by our patients and that less procedural difficulties are encountered. With increasing operator experience the total fetal loss rate to 20 weeks' gestation in our series declined to 2.1% and late complications were no more frequent than expected. In 98.4% of patients, sufficient villi were obtained for analysis. Culture failure was extremely uncommon, occurring only twice in our series. In 1.5% of patients, a follow-up amniocentesis was required, which compares favourably with other published series. It appears that many units abandoned the transcervical route before loss rates were stabilized. In units where transcervical CVS is still performed the transabdominal route is also utilized. The reverse is not true. The authors feel that both procedures have a role in modern antenatal diagnosis.

    Title An Examination of the Psychological and Behavioural Factors in the Development of Language Retardation in Twins.
    Date September 1991
    Journal Acta Geneticae Medicae Et Gemellologiae
    Excerpt

    Using therapeutic intervention, the psychological and behavioural factors in the development of language retardation in two pairs of 4-year-old MZ twins have been examined. Although some factors are common to those found in singletons with language retardation, the factors peculiar to the twin situation are highlighted.

    Title Cell-mediated Immunity in Calves Experimentally Infected with Bhv-1.
    Date February 1991
    Journal The Veterinary Record
    Title Clinical Monitoring of Steatorrhoea in Cystic Fibrosis.
    Date October 1990
    Journal Archives of Disease in Childhood
    Title Experimental Reactivation of Bovine Herpesvirus 1 (bhv-1) by Means of Corticosteroids in an Intranasal Rabbit Model.
    Date August 1990
    Journal Archives of Virology
    Excerpt

    Intranasal inoculation of the rabbit was shown to be a viable alternative to eye inoculation as a model to study latency and reactivation of bovine herpesvirus 1 (BHV-1). In four different experiments, separate groups of rabbits were intranasally inoculated with BHV-1. In two experiments some rabbits were inoculated instead with a TK-defective (TK-) mutant strain of BHV-1. The development of a specific antibody response was monitored by both virus neutralization and ELISA assays. Cell-mediated immunity was measured by means of a skin test. Many weeks after virus inoculation the rabbits were treated with corticosteroid. Antibody formation after treatment was markedly different in wild type and in TK- virus inoculated groups. In the former, virus reactivation was suggested by a sudden rise in serum antibody levels with kinetics closely resembling those reported in infected calves following corticosteroid administration, whereas in the case of the TK- group no significant increase in antibody activity was measured. Histopathological changes in trigeminal ganglia also indicated reactivation of virus in the wild-type virus infected animals. Further evidence for reactivation was obtained by virus isolation from nasal swabs after corticosteroid treatment.

    Title A Reliable Method for Establishing Viral Infection in the Rabbit by Intranasal Inoculation.
    Date May 1990
    Journal Journal of Virological Methods
    Excerpt

    Bovine herpesvirus 1 (BHV-1) infection was established in the rabbit by a novel procedure which involved virus being injected through trephine openings on either side of the nose of anaesthetised animals. This method of intranasal inoculation produced more consistent reactions to BHV-1 inoculation, and both humoral and cell-mediated immune responses to the virus were of greater magnitude compared with those following per naris instillation of virus.

    Title Ontogeny of Pancreatic Exocrine Function.
    Date April 1990
    Journal Archives of Disease in Childhood
    Excerpt

    Exocrine pancreatic proteolytic activity, determined by serial measurement of faecal chymotrypsin concentration, was investigated in 21 preterm infants (23-32 weeks' gestation) during the first 28 days of life. The overall chymotrypsin concentration range was similar to that already described in term infants showing that pancreatic chymotrypsin secretion is equally well developed at birth in the preterm infant. A chymotrypsin concentration peak, seen in term infants at 4 days, did not occur in this study until day 8, suggesting a slower initiation of pancreatic exocrine function in the preterm infant. Median faecal chymotrypsin concentrations, calculated for each baby using data from stools passed between day 2 and day 12 of life, were significantly lower in infants who were small for gestational age when compared with those who were an appropriate size for gestational age. The lower chymotrypsin concentration in infants who were small for gestational age suggests a deleterious effect of intrauterine growth retardation on pancreatic exocrine function which may be a factor in limiting postnatal catch up growth.

    Title Animal Models for Antiviral Chemotherapy.
    Date March 1990
    Journal Antiviral Research
    Excerpt

    Traditionally animal models have formed a vital part of the preclinical evaluation of new forms of antiviral therapy. A variety of models used in the past or potentially useful in the future are considered in this short review. Several valuable and complex questions concerning virus-drug interactions in vivo have been successfully addressed by means of animal models. Better understanding of drug modes of action and virus pathogenesis in the models enable even more accurate predictions to be made for the outcome of antiviral therapy in man. The complexity of virus infections in man is such that animals are likely to remain an important part in drug evaluation for many years. To this end, new developments such as improved techniques in the production of transgenic animals are opening up a variety of completely novel methods for studying inhibitors of a wider group of viruses in vivo including the human immunodeficiency virus. However, the correct interpretation of animal data requires the critical evaluation of animal models. This review will identify several important difficulties which confront those working on antiviral chemotherapy in animals and which must continue to be addressed if confidence in animal data is to be maintained.

    Title Egg and Breast Milk Based Nitrogen Sources Compared.
    Date December 1989
    Journal Archives of Disease in Childhood
    Excerpt

    A nitrogen source based on egg protein (Vamin 9 glucose) and an alternative with an amino acid profile more similar to breast milk (Vaminolact), were compared in 14 parenterally fed infants. Subjects were randomly allocated to receive one or other amino acid solution, but were otherwise given identical diets. At the start of the study the two groups did not differ significantly in postconceptual age, postnatal age, or weight. Over a six day study period on a stable intake of intravenous nutrients there was no significant difference in growth or nitrogen retention between the two groups. Plasma amino acid profiles in those receiving Vamin 9 glucose, however, were frequently abnormal. Notably, mean concentrations of potentially neurotoxic phenylalanine and tyrosine were significantly higher (140% and 420%, respectively) in patients fed Vamin 9 compared with those given Vaminolact. An amino acid solution based on the composition of breast milk protein therefore brings plasma amino acid profiles during parenteral nutrition closer to those found in breast fed infants, and reduces in particular, the risks of hyperphenylalaninaemia and hypertyrosinaemia.

    Title Intestinal Permeability As a Measure of Small Intestinal Mucosal Integrity: Correlation with Jejunal Biopsy.
    Date October 1989
    Journal African Journal of Medicine and Medical Sciences
    Excerpt

    The permeability of the small intestine was measured and jejunal biopsy performed in 39 children with gastrointestinal disorders. Intestinal permeability was measured using orally administered mannitol and lactulose as probe molecules in an isotonic solution (274 mOs/l), and the results were expressed as the ratio of the urinary excretion of the two sugars over 5 h. Urine samples were analysed for mannitol and lactulose content by high performance liquid chromatography. Children with small intestinal mucosal damage, irrespective of the cause, had a significantly lower (P less than 0.001) mannitol excretion (mean recovery 1.21% of ingested dose) than those with a normal mucosa (mean recovery 5.3%), while lactulose excretion did not differ (P greater than 0.05). The mean value of the lactulose:mannitol urinary excretion ratios was significantly higher (P less than 0.001) in subjects with an abnormal mucosa (0.98) compared to those with a normal mucosa (0.2). Using the mean plus two standard deviations of the normal mucosa group to define the upper limit of normal, all lactulose: mannitol excretion ratios from the abnormal mucosa group were above this limit. The results of this study show that the sugar permeability test is a sensitive, non-invasive screening test for jejunal mucosal damage in children and shows good correlation with jejunal biopsy results.

    Title Prenatal, Delivery, and Infant Care Under Medicaid in Three States.
    Date October 1989
    Journal Health Care Financing Review
    Excerpt

    Medicaid services and expenditures were analyzed for care during the prenatal, delivery, and post-delivery periods in three States--California, Georgia, and Michigan. Uniform data were used from the Health Care Financing Administration's Medicaid Tape-to-Tape project, 1983-84. Results indicate that from 16 to 24 percent of all births in the States of the study, during the study period, were financed by Medicaid. Overall, the study showed that more than one-half of expenditures for the study population were for the delivery hospitalization, and less than 12 percent were for prenatal care. As expected, a substantial portion of expenditures were for high-cost deliveries, up to 41 percent of total delivery payments. From 33 to 41 percent of total Medicaid expenditures for Aid to Families with Dependent Children were for pregnancy, delivery, and newborn care in 1983.

    Title Glucose-galactose Malabsorption: Demonstration of Specific Jejunal Brush Border Membrane Defect.
    Date March 1989
    Journal Gut
    Excerpt

    Jejunal brush border glucose transport was studied in a patient with glucose-galactose malabsorption and in controls, using jejunal brush border membrane vesicles (BBMV) prepared from conventional jejunal biopsies. Whereas BBMV from controls showed a seven-fold enhancement of D-glucose uptake in the presence of an inwardly directed sodium gradient compared with its absence, no such enhancement was seen in the patient's vesicles. In BBMV from the patient, initial D-glucose uptake under sodium gradient conditions was only 10% of the mean control value. In contrast, sodium/proton exchange in BBMV from the patient was intact. These data provide the first unequivocal evidence that the jejunal brush border membrane is the site of a specific defect in sodium dependent glucose transport in glucose-galactose malabsorption. Measurement of glucose uptake by BBMV may well be the optimal diagnostic technique in this disorder.

    Title Changes in Phospholipid Metabolism Dependent on Calcium-regulated Myoblast Fusion.
    Date March 1989
    Journal Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire
    Excerpt

    Fusion-competent myoblasts can be prevented from fusing (differentiating) by reducing medium calcium concentrations from 1.65 mM to less than 50 microM. Fusion is completely retarded after 24 h but is noticeable after 48 h and significant after 72 h in low-calcium medium. After 24 h in low-calcium medium, a rapid, synchronous fusion can be initiated by return to normal (high-calcium) medium. Calcium content increases over threefold during myoblast differentiation and closely parallels the fusion process. Phospholipid content is also dependent upon the state of differentiation. Myotubes (fused myoblasts) have an almost twofold greater content of lipid phosphate per milligram of protein compared with that of myoblasts; this increase is localized to increased contents of phosphatidylcholine and pooled phosphatidylinositol - phosphatidylserine. Phospholipid synthesis (32Pi incorporation) is markedly stimulated four- to five-fold when myoblasts grown in low-calcium medium are switched to normal medium. These significant increases are observed in all the major phospholipids studied, predominantly in phosphatidylcholine and pooled phosphatidylinositol - phosphatidylserine, and most noticeably in phosphatidylinositol 4,5-bisphosphate. Furthermore, we show that phosphatidylinositol 4,5-bisphosphate prelabelled with myo-[2-3H]inositol is rapidly degraded after switching from low-calcium medium to normal medium. These changes are not observed in myotubes treated similarly, which suggests that the changes in phospholipid metabolism may be fusion related. These results support a proposal by another author, which suggests that phosphatidylinositol 4,5-bisphosphate breakdown may play an important regulating role in myoblast differentiation.

    Title Nonlipid Formula Components and Fat Absorption in the Low-birth-weight Newborn.
    Date February 1989
    Journal The American Journal of Clinical Nutrition
    Excerpt

    The relationship between nonlipid formula components and fat absorption in newborns is largely uninvestigated. Two formulas of identical fat blend but different protein quality and acid-base properties were fed to two groups of babies from birth and during 3-5 d balance periods in the third week of life. Babies receiving a formula of higher acidity containing predominantly curd protein absorbed a significantly lower percentage of their fat and nitrogen intake than babies receiving a curd-and-whey protein formula (fat absorptions of 73 +/- 11.0 and 85 +/- 8.0%, means +/- SD, p less than 0.04; N absorptions of 90 +/- 3.0 and 93 +/- 1.0%, p less than 0.03, respectively). The feces of the curd-formula babies contained a smaller proportion of long-chain, saturated fatty acids and a larger proportion of shorter-chain and unsaturated fatty acids. Fatty acid type and triglyceride structure are not the only factors influencing fat absorption in newborns. Other formula components may need modification to achieve maximum fat absorption.

    Title Faecal Chymotrypsin Concentrations in Neonates with Cystic Fibrosis and Healthy Controls.
    Date January 1989
    Journal Archives of Disease in Childhood
    Excerpt

    Specimens of meconium and random stools were collected sequentially from 25 healthy newborn babies over the first 8-14 days of life. The stool chymotrypsin concentrations increased from birth to a maximum at 4 days of age and then fell again over the next four days. The lowest individual stool concentrations either side of the four day peak were both, coincidentally, 120 micrograms/g stool. In a second group of 22 newborn babies suspected of meconium ileus and later confirmed to have cystic fibrosis, faecal chymotrypsin concentrations were all appreciably reduced. In eight babies, also with suspected meconium ileus but with negative sweat tests, chymotrypsin concentrations were within the healthy newborn range. Measuring faecal chymotrypsin concentrations is a reliable procedure for identifying pancreatic exocrine insufficiency in the newborn.

    Title Urinary Mannitol: Lactulose Excretion Ratios and Jejunal Mucosal Structure.
    Date November 1988
    Journal Archives of Disease in Childhood
    Excerpt

    A dual sugar (mannitol, lactulose) absorption test was evaluated using an iso-osmolar oral dose in two groups of children: a study group of 43 children divided into five subgroups, based on severity of mucosal damage, and a control group of 53 children with histologically normal jejunal biopsy specimens. After an oral dose, the three hour urinary mannitol: lactulose ratios in the control group showed a highly significant positive correlation with body surface area. After correction for the body surface area relationship, a control lower limit was defined by the mean -2SD of the log10 transformed control mannitol: lactulose ratios. Specificity and sensitivity for severe villous atrophy was 98% and 95% respectively but the sensitivity declined rapidly with decreasing degrees of mucosal damage, and the test would not therefore be an adequate screening procedure for all enteropathies. In sequential studies in 18 children, the changes in the mannitol: lactulose ratio were consistent with the changes in mucosal structure induced by gluten challenge or gluten withdrawal. The test may therefore have a role in any sequential study of lesions of the mucosa of the small intestine.

    Title Faecal Chymotrypsin: a Reliable Index of Exocrine Pancreatic Function.
    Date October 1988
    Journal Archives of Disease in Childhood
    Excerpt

    Simultaneous measurements of duodenal and faecal chymotrypsin were made in 30 children aged 3 weeks to 14 years. Apparent chymotrypsin secretion rates measured after stimulation with pancreozymin were compared with the mean faecal chymotrypsin concentration derived from three stool specimens collected at random within 72 hours of the intraduodenal test. In the 25 children who responded to pancreozymin stimulation the mean faecal chymotrypsin concentration was significantly positively correlated with the apparent chymotrypsin secretion rate. Correlation using single specimen stools collected at random was appreciably poorer. In the five children with undetectable or only traces of chymotrypsin in the duodenum after stimulation, the mean faecal chymotrypsin concentrations were only 3-10% of the lower limit of the reference interval. In a second group of 46 children with cystic fibrosis proved by sweat tests and clinical evidence of malabsorption, the chymotrypsin concentration measured in a single stool specimen collected at random was unequivocally subnormal in each case. Faecal chymotrypsin measurement is a rapid, simple, cheap, readily repeated, non-invasive test of high specificity and sensitivity. Faecal chymotrypsin should be measured before contemplating intraduodenal tests of pancreatic function.

    Title Effect of Reducing the Boost Dose of Fecundin on the Reproductive Performances of Previously Vaccinated Ewes.
    Date September 1988
    Journal Australian Veterinary Journal
    Title Postnatal Development of Disaccharidase Activities in Jejunal Fluid of Preterm Neonates.
    Date February 1987
    Journal Gut
    Excerpt

    Because human fetuses of 26-30 weeks gestation are known to have low levels of intestinal mucosal lactase activity, it has been assumed that live born preterm neonates of comparable gestational age are also lactase deficient. We have previously shown that disaccharidase activities in jejunal fluid in infants are highly significantly correlated with enzyme activities in the adjacent mucosa. We have now measured disaccharidase activities cross-sectionally and longitudinally in the jejunal fluid of a group of very preterm neonates of 26-29 weeks gestation who were fed with pasteurised human milk. Lactase activity was within the normal range for older infants and children within the first week of life. Sucrase: lactase ratios fell significantly in the second and third weeks of life, strongly suggesting a further increase in lactase activity. This increase was independent of postconceptional age. Preterm neonates are not as lactase deficient as previously believed, and this has implications in the search for optimal feeding regimes.

    Title The Coexistence of Carcinoid Tumor and Crohn's Disease.
    Date September 1986
    Journal Journal of Clinical Gastroenterology
    Excerpt

    We report what we take to be the ninth case of an intestinal carcinoid tumor coexisting with Crohn's disease; we believe that it is also the first case of Crohn's disease in which the carcinoid tumor involved both the small and large bowel, as well as the appendix. The two lesions may be remarkably similar in their clinical presentation, gross appearances, and radiologic features. We suggest that the actual incidence of their coexistence may be greater than the few reports suggest.

    Title Understanding the Processes of Consultation: Some Models and Their Uses.
    Date June 1986
    Journal Medical Teacher
    Title How to Make and Use Video in Teaching.
    Date April 1986
    Journal Medical Teacher
    Title Up, Up, and Away: Aeromedical Transport in Ems ... Open Forum.
    Date November 1985
    Journal Emergency Medical Services
    Title The Effect of the Uk Aircrew Chemical Defence Assembly on Thermal Strain.
    Date April 1985
    Journal Aviation, Space, and Environmental Medicine
    Excerpt

    The thermal strain imposed on helicopter aircrew by chemical protective (NBC) clothing in summer in Germany has been assessed in a laboratory simulation. The environmental conditions used were dry bulb temperature 35 degrees C, wet bulb temperature 19 degrees C and a wind speed of 2.0 m X s-1. The NBC equipment imposed a significant thermal strain on the crewman when compared with standard summer flying clothing, but not on the pilot whose tasks involve lower energy expenditures. Deep body temperature exceeded 37.6 degrees C and a significant degree of dehydration (1% of body weight) also occurred, despite the availability of a drinking facility in the respirator. It is recommended that the only practical way of preventing thermal strain in helicopter crewmen under NBC conditions is by providing personal conditioning.

    Title The Energy Expenditure of Helicopter Pilots.
    Date November 1984
    Journal Aviation, Space, and Environmental Medicine
    Excerpt

    The energy expenditure of Army Air Corps and Royal Air Force pilots has been measured during flight in Gazelle and Puma helicopters respectively. Heart rates were also recorded. The results were compared with resting values obtained in the crewroom before flight, and confirmed the findings of other authors that the energy cost of flying helicopters in level flight is about 50% higher than that of sitting at rest.

    Title Disaccharidase Activities in Jejunal Fluid.
    Date November 1983
    Journal Archives of Disease in Childhood
    Excerpt

    Jejunal fluid and mucosal tissue were obtained simultaneously from the same jejunal site in a group of 29 children by a modified biopsy procedure. Lactase, maltase, and sucrase activities were measured in both fluid and mucosal specimens using the same analytical method. The fluid enzyme activities showed highly significant positive correlations with the same enzyme activity in the relevant tissue samples. Relative concentrations of disaccharidase enzymes represented by sucrase: lactase activity ratios also showed a highly significant positive correlation between fluid and tissue. This close relation suggests that the mucosa is the sole or predominant source of disaccharidase activity in the intestinal fluid. The results of kinetic studies comparing tissue and fluid enzyme characteristics also indicate a mucosal origin for the fluid enzyme activities. We conclude that disaccharidase activities in jejunal fluid reflect closely local tissue values and that these measurements may be useful in assessing mucosal enzyme activity in infants in whom jejunal biopsy is not possible.

    Title Development of Intestinal Disaccharidases in Preterm Infants.
    Date October 1983
    Journal Lancet
    Title The 'oxylog': an Evaluation.
    Date February 1983
    Journal Ergonomics
    Title The Effect of Head Cooling on Deep Body Temperature and Thermal Comfort in Man.
    Date October 1982
    Journal Aviation, Space, and Environmental Medicine
    Excerpt

    A liquid conditioned hood (LCH) made of stretch nylon was used to investigate the effect of head cooling on deep body temperature and thermal comfort in man. Six male subjects each performed two experiments of 2 h duration, in a climatic chamber, in conditions of dry bulb temperature 40 degrees C, wet bulb temperature 29 degrees C and 50 mm black globe temperature 50 degrees C. In one experiment head cooling was given during the first hour and in the other during the second hour. In both experiment, auditory canal (Tac) and oesophageal (Toe) temperatures increased during the first hour. During the second hour, without head cooling Tac and Toe continued to increase, whilst with head cooling no further increase in either was observed with an improvement in both head and body thermal comfort and with a small decrease in mean skin temperature.

    Title Maximal Oxygen Uptake: Its Measurement, Application, and Limitations.
    Date April 1981
    Journal Aviation, Space, and Environmental Medicine
    Excerpt

    Maximal aerobic power (VO2 max) was determined by direct measurement in 10 male subjects whilst exercising on a bicycle ergometer, and whilst running uphill on a treadmill at speeds of 10 and 12 km/h. There was no significant difference between VO2 max measured at the two treadmill speeds, but the VO2 max measured on the bicycle was 20% lower than on the treadmill. An estimate of the variance of the treadmill determined VO2 max was obtained from repeated measurements on five subjects. The 95% tolerance interval about a single measurement of VO2 max was +/- 7.8 ml.kg-1.min-11. It is recommended that when indirect methods for determining VO2 max are calibrated against the direct method, the latter should be based upon the treadmill. Reservations are expressed concerning the value of the direct method for determining VO2 max, and of the concept of VO2 max as a measure of physical fitness.

    Title A Comparison of Some Indirect Methods for Predicting Maximal Oxygen Uptake.
    Date April 1981
    Journal Aviation, Space, and Environmental Medicine
    Excerpt

    Nine male subjects took part in a comparative evaluation of four indirect tests commonly used for predicting maximum aerobic power (VO2 max). In three of these tests (involving cycling, stepping and walking) VO2 max was predicted from submaximal heart rates; in the fourth, VO2 max was predicted from the time taken to run 2 km. Additionally, VO2 max was predicted from the body fat content. All predicted values were compared with the VO2 max determined directly on a treadmill. The best estimates of VO2 max were provided by the timed run, and by the step test. Both heart rate measured during walking and body fat content proved totally inadequate for the reliable prediction of VO2 max. Taking into account such factors as cost, safety, and the time required for testing, it is concluded that the timed run is the submaximal test most suited to the indirect determination of VO2 max.

    Title Synovial Sarcoma: an Electron Microscopic Study of Monophasic and Biphasic Forms.
    Date July 1980
    Journal Cancer
    Excerpt

    Seven cases of synovial sarcoma were studied by electron microscopy. The 4 cases of the monophasic spindle type contained elongated cells arranged in sheets and cords; ultrastructurally the cells contained many cytoplasmic processes and were scattered in an amorphous matrix. The monophasic spindle type demonstrates ultrastructural characteristics that are unique and serve to differentiate it from the biphasic pattern and from fibrosarcoma. Three cases of the biphasic variety demonstrated cytologic characteristics of a true glandular epithelium and a malignant spindle cell stroma. The epithelial nature of the biphasic variety is a feature that raises doubt whether synovium is the stem cell.

    Title Duodenal Bile Acids in Infants with Protracted Diarrhoea.
    Date June 1979
    Journal Archives of Disease in Childhood
    Excerpt

    Bile acids were estimated in the duodenum of infants with protracted diarrhoea and compared with those in a control group. Significantly lower levels of total bile acids were found in infants with protracted diarrhoea, a finding which may be due to ileal dysfunction. Low concentrations of total bile acids may contribute to the poor nutritional state of these patients by impairing the normal digestion and absorption of dietary fat and fat-soluble vitamins. The absence of deconjugated bile acids in the duodenal juice of most infants with protracted diarrhoea suggests that they do not contribute significantly to the pathophysiology of this disorder.

    Title Validity of Fecal Coliforms, Total Coliforms, and Fecal Streptococci As Indicators of Viruses in Chlorinated Primary Sewage Effluents.
    Date March 1979
    Journal Applied and Environmental Microbiology
    Excerpt

    Quantities of combined chlorine that usually destroyed more than 99.999% of the indigenous fecal coliforms, total coliforms, and fecal streptococci in primary sewage effluents destroyed only 85 to 99% of the indigenous viruses present. Viruses were recovered from five of eight chlorinated primary effluents from which fecal coliforms were not recovered by standard most-probable-number procedures. The limited volumes of such chlorinated effluents that can be tested for indicator bacteria with currently available multiple-tube and membrane filter techniques restrict the value of fecal coliforms, fecal streptococci, and even total coliforms as indicators of viruses in these effluents. Although fecal coliforms and fecal streptococci are useful indicators of viruses in effluents from which these bacteria are recovered, the absence of these bacteria and even total coliforms from disinfected effluents (in standard tests) does not assure that viruses are also absent.

    Title Reduction of Bile Acid Loss in Cystic Fibrosis by Dietary Means.
    Date October 1978
    Journal Archives of Disease in Childhood
    Excerpt

    On a 'normal' diet increased faecal bile acid excretion was found in 14 of 16 children with cystic fibrosis who had steatorrhoea, but excretion was normal in 2 such children without steatorrhoea. The 16 children with steatorrhoea took 3 regimens of diet and therapy: a 'normal' diet with pancreatic enzyme supplements, a diet of reduced long-chain triglycerides with added medium-chain triglycerides, and the same diet with added pancreatic enzyme supplements. On each of these three regimens steatorrhoea and faecal bile acid loss were significantly less than on no treatment, with the lowest excretions occurring on the diet of reduced long-chain triglycerides with added medium-chain triglycerides and pancreatic enzyme supplements. Although a reduction in steatorrhoea was nearly always accompanied by a decrease in bile acid excretion, the initial bile acid loss was very variable and could not be predicted for any given degree of steatorrhoea. This suggests that at least one other factor, possibly liver disease or bile acid pool size, influences bile acid loss in the faeces.

    Title Duodenal Bile Acid Conjugation Patterns and Dietary Sulphur Amino Acids in the Newborn.
    Date May 1978
    Journal Gut
    Excerpt

    Patterns of glycine and taurine conjugation of bile acids in duodenal juice have been studied in 20 low birth weight babies at 12 and 22 days of age. They were fed from birth on one of three feeds containing different amounts of taurine and its precursors, cysteine and methionone. Taurine conjugation predominated in those fed on human milk throughout the first three weeks of life. In those fed on SMA or S26 infant feeding formulae, both of which contain very little taurine, concentrations of glycine conjugates were found to exceed those of taurine conjugates by the 12th day. The low glycine-taurine conjugate ratios previously described in newborn babies are, therefore, probably related to the taurine content of the milk which they received. Glycine-taurine conjugate ratios less than 1.0 occur in breast fed infants during the first three weeks of life.

    Title Urinary 5-hydroxyindoleacetic Acid in 8-hour Collections As an Aid in Diagnosis of Coeliac Disease.
    Date May 1978
    Journal Archives of Disease in Childhood
    Excerpt

    8-hour urine excretions of 5-hydroxyindoleacetic acid (5-HIAA) were measured in 18 children with coeliac disease before treatment and the results expressed as microgram 5-HIAA/mg creatinine. Similar measurements were made on urine collections from an age-matched control group of 24 children. Significantly higher values of 5-HIAA excretion were found in children with untreated coeliac disease. Measurement of the 5-HIAA: creatinine ratio in 8-hour urine collections is therefore proposed as an aid in the diagnosis of coeliac disease.

    Title Congenital Pseudarthrosis of Long Bones: a Clinical, Radiographic, Histologic and Ultrastructural Study.
    Date March 1978
    Journal Clinical Orthopaedics and Related Research
    Excerpt

    Sixteen patients with pseudarthrosis of the tibia and one of the radius were evaluated clinically, radiograpically, and microscopically and separated into 3 groups; 8 had neurofibromatosis clinically, 3 had fibrous dysplasia histologically, and 6 had no evidence of either neurofibromatosis or fibrous dysplasia. Prognosis and therapy were determined by correlated clinical, radiographic, and histological observations. Fracture before age 2 years carried a poor prognosis. Electron microscopy allowed neither differentiation among these fibrous lesions, nor any clue to their origin, nor did it support the concept of a neural or vascular derivation.

    Title A Diy Human Calorimeter for 100 Pounds.
    Date October 1977
    Journal The Proceedings of the Nutrition Society
    Title Preparation of Mental Health Personnel for the Delivery of Mental Retardation Services.
    Date May 1977
    Journal Community Mental Health Journal
    Excerpt

    The developmental experience of an urban community mental health-mental retardation center is presented as a guiding model for other community mental health centers interested in "tooling up" their mental retardation services. Surveying personnel needs, establishing educational objectives tailored to personnel, presenting specific knowledge about mental retardation, clarifying mandates for community mental health-mental retardation service, and two conceptual frameworks for service delivery are elaborated.

    Title Cast Brace Treatment of Plateau and Bicondylar Fractures of the Proximal Tibia.
    Date October 1976
    Journal Clinical Orthopaedics and Related Research
    Excerpt

    Twenty-nine patients with 30 intraarticular proximal tibial fractures were treated with early application of a cast brace. All fractures united, knee motion was excellent or good in all but one patient. The fracture fragments did not lose position after cast brace application. Varus or valgus deformities could be corrected and maintained. Ninety per cent had no pain at follow-up. Hospital stay was as short as two days and generally under two weeks.

    Title Elevated Serum Igg4 Levels in Cystic Fibrosis Patients.
    Date September 1976
    Journal Clinical Allergy
    Excerpt

    The quantitative measurement of the IgG subclass composition of the sera from sixteen patients with cystic fibrosis has revealed grossly elevated levels of IgG4 in seven patients. The possible significance of this observation is discussed in relation to recent reports of a high incidence of immediate-type hypersensitivity in such patients.

    Title Proceedings: Stimulation of Intestinal Cyclic Amp by a Heat Stable Toxin of Escherichia Coli 0148.
    Date August 1976
    Journal Gut
    Title Duodenal Bile Acids in Infancy.
    Date March 1976
    Journal Archives of Disease in Childhood
    Excerpt

    Duodenal bile acids have been estimated in three age groups in infancy from birth to 7 months, and age-related changes have been shown. The lowest concentrations of duodenal bile acids occurred in the youngest infants, and increasing concentrations were found with increasing age. Taurine conjugated bile acids predominated in early infancy, while in older infants bile acids were mainly conjugated with glycine. The probable presence of taurolithocholic acid in the duodenal bil of 2 newborns before the establishment of a gastrointestinal microflora remains to be confirmed, but could result either from transplacental passage of secondary bile acids or from endogenous synthesis by the fetal liver.

    Title Comparative Trial of Pancrex V Forte and Nutrizym in Treatment of Malabsorption in Cystic Fibrosis.
    Date December 1974
    Journal British Medical Journal
    Title Endoplasmic Reticulum Size and Morphology in Bone Disorders. Relation to Protein Synthesis and Malignancy.
    Date September 1974
    Journal Clinical Orthopaedics and Related Research
    Title Congenital Pseudarthrosis of the Radius.
    Date April 1974
    Journal The Journal of Bone and Joint Surgery. American Volume
    Title The Stability of Ethanol in Stored Blood. I. Important Variables and Interpretation of Results.
    Date November 1973
    Journal Analytica Chimica Acta
    Title The Stability of Ethanol in Stored Blood. Ii. The Mechanism of Ethanol Oxidation.
    Date November 1973
    Journal Analytica Chimica Acta
    Title An Exploratory Study of Interaction Amongst British and Immigrant Children.
    Date October 1973
    Journal The British Journal of Social and Clinical Psychology
    Title Objective Measurement of Motor Skill Acquisition.
    Date September 1973
    Journal Physical Therapy
    Title Uterine Bleeding Following Insertion of Two Iud's.
    Date September 1972
    Journal Alaska Medicine
    Title Increased Excretion of 5-hydroxyindoleacetic Acid in Urine of Children with Untreated Coeliac Disease.
    Date August 1972
    Journal Archives of Disease in Childhood
    Title Insulin Excretion in Cystic Fibrosis.
    Date June 1972
    Journal Archives of Disease in Childhood
    Title Gamma Radiation Effects on Sitophilus Zeamais and S. Granarius.
    Date April 1972
    Journal Journal of Economic Entomology
    Title Inhibition of Sugar Transport by Cystic Fibrosis Plasma.
    Date February 1972
    Journal Gut
    Title Plasma Growth Hormone Levels in Children with the Prader-willi Syndrome.
    Date November 1971
    Journal Australian Paediatric Journal
    Title Inhibition of Sugar Transport by Plasma from Cystic-fibrosis Patients.
    Date November 1971
    Journal Lancet
    Title Growth Hormone Response to Oral Glucose Load in Untreated Diabetic Children.
    Date June 1971
    Journal Archives of Disease in Childhood
    Title Immediate Pharyngeal Repair After Pharyngo-laryngectomy Using the Medially Based Chest Flap.
    Date December 1970
    Journal The Journal of Laryngology and Otology
    Title Thoracotracheostomy After Resection of the Larynx and Cervical Trachea for Cancer.
    Date December 1970
    Journal The Journal of Laryngology and Otology
    Title Deliberate Delayed Primary Skin-grafting.
    Date December 1970
    Journal The British Journal of Surgery
    Title Infusion Thrombophlebitis.
    Date October 1970
    Journal The British Journal of Clinical Practice
    Title Horizontal Incisions for Radical Neck Dissections.
    Date July 1970
    Journal Archives of Otolaryngology (chicago, Ill. : 1960)
    Title Plasma Insulin and Growth Hormone Levels in Untreated Diabetic Children.
    Date June 1970
    Journal Archives of Disease in Childhood
    Title Electron Microscopy of the Skin of the Teleost, Hippoglossoides Elassodon.
    Date March 1970
    Journal Zeitschrift Für Zellforschung Und Mikroskopische Anatomie (vienna, Austria : 1948)
    Title The Photoinhibition of Coleoptile Growth and Its Bearing on Phototropism. Anl-7409.
    Date February 1970
    Journal Anl
    Title Nasal Polyposis.
    Date January 1970
    Journal Postgraduate Medical Journal
    Title Larval Skin of the Flathead Sole, Hippoglossoides Elassodon.
    Date January 1970
    Journal Zeitschrift Für Zellforschung Und Mikroskopische Anatomie (vienna, Austria : 1948)
    Title Collagen Formation and Calcification in Teleost Scales.
    Date August 1969
    Journal Zeitschrift Für Zellforschung Und Mikroskopische Anatomie (vienna, Austria : 1948)
    Title Growth-hormone Response to Oral Glucose in Children with Simple Obesity.
    Date July 1969
    Journal Lancet
    Title Growth Hormone Secretion Provoked by Insulin-induced Hypoglycaemia in Children of Short Stature.
    Date July 1967
    Journal Archives of Disease in Childhood
    Title Growth Hormone-induced Nitrogen Retention in Children of Short Stature.
    Date July 1967
    Journal Archives of Disease in Childhood
    Title Retrograde Nailing of Femur Shaft Fractures Through the Intercondylar Notch for Specific Indications: 10 Years Experience.
    Date
    Journal Surgical Technology International
    Title Composition and Structure of Starch from Taproots of Contrasting Genotypes of Medicago Sativa L.
    Date
    Journal Plant Physiology
    Excerpt

    The objective of this study was to examine the composition and branch chain lengths of alfalfa (Medicago sativa L.) taproot starch during starch utilization and reaccumulation in response to defoliation. Genotypes were propagated vegetatively and well-established plants were sampled at defoliation and at weekly intervals thereafter. Starch granules from root tissues were dispersed in dimethyl sulfoxide and starch components separated using gel permeation chromatography. Root starches also were debranched enzymically, and branch chain lengths were examined. Results indicate that, irrespective of starch concentration, starch from taproots of the high starch genotype was composed of approximately 80% high molecular weight starch with I(2)-Kl absorbance characteristics similar to amylopectin. The remaining 20% of the starch was low molecular weight with I(2)-Kl absorbance characteristics similar to amylose. Starches of the low starch genotype contained approximately 85% high molecular weight polysaccharide at high root starch concentrations (>50 grams per kilogram). At low root starch concentrations (<10 grams per kilogram), starch from the low starch genotype had nearly equal proportions of low and high molecular weight polysaccharide. The I(2)-Kl absorbance properties of the low molecular weight starches from roots of the low starch genotype indicated that some branching may be present. The distribution of chain lengths from amylopectin did not change during starch degradation and reaccumulation for the high starch genotype. In the low starch genotype, the proportion of low molecular weight branches having a degree of polymerization between 1 and 30 was decreased at the very low starch concentrations observed on the 14th day of regrowth. Higher concentrations and/or quantities of starch in roots of the high starch genotype were not associated with greater rate of herbage regrowth, when compared to the low starch genotype.

    Title The Impact of Variant Histology on the Outcome of Bladder Cancer Treated with Curative Intent.
    Date
    Journal Urologic Oncology
    Excerpt

    Patient risk stratification is essential for optimal management of patients with bladder cancer. Risk status determines the application and timing of therapeutic interventions such as repeat transurethral resection, intravesical chemo- and immunotherapy, systemic chemotherapy, and radical cystectomy. One key factor in such risk stratification appears to be the presence of variant histologic patterns in the bladder tumor. More than 90% of tumors are conventional urothelial carcinoma, and the rest consist of urothelial carcinoma with aberrant differentiation (squamous/glandular differentiation, small cell carcinoma, sarcomatoid carcinoma, and micropapillary carcinoma) or nonurothelial carcinoma (squamous cell carcinoma and adenocarcinoma). In this review, we focus on the implications of aberrant differentiation on the management of patients with bladder cancer. All of the variant histologies portend a worse prognosis than pure urothelial carcinoma. Although radical cystectomy remains the mainstay of treatment in all forms of bladder cancer, we highlight the use of neoadjuvant chemotherapy in patients with subtypes responsive to such therapy.

    Title The Role of Radical Cystectomy in Patients with Clinical T4b Bladder Cancer.
    Date
    Journal Urologic Oncology
    Excerpt

    Patients with clinical T4b bladder cancer (extension to pelvic wall and/or adjacent organs other than prostate, vagina, or uterus) are commonly considered unresectable. We hypothesized that select patients might achieve durable benefit from multiagent chemotherapy and extirpative surgery.

    Title Retrograde Nailing of Femur Shaft Fractures Through the Intercondylar Notch for Specific Indications: 10 Years Experience.
    Date
    Journal Surgical Technology International
    Excerpt

    Closed antegrade intramedullary nailing is the current standard of care for the treatment of femoral shaft fractures. This technique has been shown to have excellent results demonstrated by a high rate of fracture union and the low incidence of infection. However, there are complications specific to antegrade intramedullary nailing, as well as specific injury patterns that make this treatment less attractive.

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