[What do women think of pelvic examination and what are our lessons?].
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Biomedical subjects
Publications and source records attributed to B Kaplan.
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BACKGROUND: It has been well documented that a regimen of mycophenolate mofetil (MMF), cyclosporine (CsA), and prednisone (Pred) reduces the incidence of acute rejection in renal transplant recipients, as compared with previous regimens based on azathioprine (AZA), CsA, and Pred. In the general renal transplant patient population, immunosuppressive regimens that include MMF are usually well tolerated. It is not clear whether this holds true for older transplant recipients, who may be more susceptible to complications from the greater immunosuppression conferred by MMF. METHODS: We retrospectively analyzed our geriatric renal transplant population (age >60 years, 1990-1998) and compared a cohort of 46 patients treated with AZA, Pred, and CsA to a cohort of 45 patients treated with MMF, Pred, and CsA. RESULTS: There were no significant differences between the groups with regard to pretransplantation demographics. Patient and graft survival during the first year was not significantly different between the groups. During the first year of follow-up, we observed 27 infections requiring hospitalization in 15 patients in the MMF-treated group as compared with 10 infections in 7 patients in the AZA-treated group. A Cox proportional hazard model accounting for the above mentioned covariates isolated MMF versus AZA as a significant risk factor for the occurrence of serious infectious events (all: P<0.01; cytomegalovirus, fungal: P<0.01). CONCLUSION: We conclude that an immunosuppressive regimen of MMF, CsA, and Pred seems to be correlated with an increased incidence of infectious adverse events as compared with AZA, CsA, and Pred in elderly patients.
BACKGROUND: A number of factors have been implicated in decreasing long-term renal graft survival. Factors such as living versus cadaveric donor status, acute rejection, and HLA matching have been studied in detail. Mild obesity defined as a body mass index (BMI) of >25 has been found to have a deleterious effect on a number of physiologic processes. We studied the effect of a BMI >25 on long-term renal transplantation outcome. METHODS: A total of 405 patients who underwent transplantation at Saint Barnabas Medical Center from 1990 to 1997 were evaluated. All known variables impacting on long-term graft function were collected. Multivariate analysis utilizing the Cox-proportional hazard model and Kaplan-Meier actuarial survival were applied to these risk factors. RESULTS: BMI >25 was isolated as an independent risk factor for both decreased graft survival and patient survival (relative risk 2.0 for each). Cadaveric donor status, acute rejection, and use of azathioprine versus mycophenolate mofetil were the only other significant risk factors. CONCLUSIONS: Mild obesity before transplantation has a negative impact on long-term renal graft and patient survival.
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With intestine transplants the allograft is dependent on itself for maintenance of adequate immunosuppression. We evaluated an intestinal transplant recipient who required very large doses of either tacrolimus or cyclosporine emulsion to achieve acceptable blood concentrations. Pharmacokinetic studies revealed bioavailabilities of 2% and 6% respectively, while D-xylose and B12 absorption were found to be within normal limits and fecal fat was only slightly increased, suggesting that there was a selective absorptive defect for these drugs. Biopsies of the allograft ileum revealed a high P-glycoprotein activity compared to the jejunum or to intestinal biopsies from other normal subjects. This may be a contributing factor to poor immunosuppressive drug absorption in this patient and others.
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Biochemical markers for Alzheimer's disease (AD) are of great value for precise diagnosis and in studies of the pathogenetic processes of this disease. A new biochemical assay allowing to differentiate AD from other forms of dementia is described. The assay is based on the extraction of amyloid beta (A beta) from milligram amounts of brain tissue by using 20% acetonitrile in 0.1% trifluoroacetic acid and its detection by Western blotting. The presence of the 4 kDa A beta was demonstrated in all cases of AD (n = 8) that were diagnosed by the independent histopathological examination of the postmortem tissues. No A beta was found in tissue extracts from seven out of eight cases of other forms of dementia. In contrast to other biochemical techniques of A beta detection in brain, the developed assay is simple; it does not require any special equipment and allows detection of A beta using milligram amounts of brain tissue.
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OBJECTIVE: To determine whether a change occurs in fetal middle-cerebral and umbilical artery flow after glucose challenge testing. METHOD: Fetal middle-cerebral and umbilical artery flow was assessed by Color Dopppler technology in 21 pregnant patients before and after the 50-g glucose challenge test. The resistance index (IR) was evaluated separately for each vessel. Statistical significance was determined by Chi-square test and repeated measurement analysis with two co-variates. RESULTS: After glucose ingestion the RI was significantly decreased in the middle-cerebral artery, but not in the umbilical artery. A significant increase in RI was recorded in the umbilical artery when maternal plasma glucose level exceeded 102 mg%. CONCLUSION: Maternal ingestion of glucose significantly alters blood flow velocimetry in the fetal middle-cerebral and umbilical arteries. These changes may lead to the misinterpretation of normal results. It is therefore recommended that sonographic flow velocimetry assessment not be performed early after concentrated glucose ingestion.
This article described micromethods useful for the extraction, purification, and amino acid sequencing of amyloid proteins contained in minute specimens obtained from patients with systemic forms of amyloidosis. We posit that these procedures can also be applied to the biochemical characterization of cerebral amyloid deposits. The selection of the techniques is dependent on the type of sample to be extracted (fresh or formalin fixed) as well as the amount of congophilic material present. Although amyloid proteins are isolated and purified more easily from fresh tissue, it must be noted that formalin-fixed specimens are available more readily for analysis due to the common diagnostic use of fine needle tissue biopsies and are therefore, important for both current and retrospective studies. Remarkably, despite the expected difficulties associated with formalin treatment we were able to extract and sequence amyloid proteins from fixed tissues presumably due to the resistance of amyloid to formalin cross-linking. Through the continued development of techniques for small-scale protein separation and application of highly sensitive microsequencing and mass spectral methods, exact identification of the protein contained in fibrillar amyloid deposits can be determined. Such information has therapeutic and prognostic relevance and can increase our understanding of the pathogenesis of amyloidosis.
STUDY OBJECTIVE: To identify historical and physical examination findings that are predictive of ectopic pregnancy (EP) in pregnant patients with abdominal pain or bleeding. METHODS: This study was conducted in an urban academic emergency department as a prospective observational study of consecutive patients from August 1, 1991, to August 31, 1992, who had abdominal pain or vaginal bleeding and a positive beta-human chorionic gonadotropin level. Patients were excluded if they had a diagnostic ultrasound during a previous visit, or if the uterine size was larger than 12 weeks by pelvic examination. Data were analyzed using chi2 with a P value less than. 05 identified as significant. Odds ratios were determined for significant variables. A classification and regression tree analysis was then performed using the predictive variables to derive a decision tree. RESULTS: Four hundred forty-one patients were enrolled, 57 of whom (13%) had an EP. Factors by history that increased the risk of EP included pain that was described as moderate to severe, lateral, or sharp. Pain located in the midline decreased the risk of EP. A history of previous intrauterine device use, infertility, prior pelvic surgery, or tubal ligation were each found to be predictive. On physical examination, the presence of peritoneal signs, cervical motion tenderness, or lateral or bilateral abdominal or pelvic tenderness increased the risk of EP. A uterine size larger than 8 weeks by pelvic examination decreased the risk of EP. Combinations of predictive variables identified subsets of patients with either an increased or decreased frequency of EP, but in no case was a combination identified that would confirm or exclude this diagnosis with a high degree of certainty. CONCLUSION: History and physical examination findings predictive of EP were identified. However, no constellation of findings could confirm or exclude this diagnosis with a high degree of reliability.
Abdominal pain occurs frequently in renal transplant recipients receiving mycophenolate mofetil (MMF) therapy. The cause of this abdominal pain has not been fully elucidated, but may involve local irritation, as well as inhibition of rapidly dividing cells of the gastrointestinal (GI) tract. This milieu of inflammation and added immunosuppression is conducive to activation of cytomegalovirus (CMV). We therefore sought to find the prevalence of active CMV in patients presenting with abdominal pain on maintenance MMF therapy. All patients receiving a renal transplant at our center from March 1, 1997, to September 1, 1997, were studied. Any patient presenting with midepigastric pain for greater than 3 days underwent esophagogastroduodenoscopy (EGD) with biopsy. CMV was diagnosed by the presence of inclusion bodies and immunohistochemical studies. Ten patients presented with persistent midepigastric pain; nine of these patients had evidence of GI CMV. Patients who were CMV negative and received an allograft from CMV-positive donors and those with leukopenia were at significantly increased risk for the development of abdominal pain. In our study population, the majority of patients on maintenance MMF therapy who presented with persistent midepigastric pain had evidence of active CMV infection in the upper gastrointestinal tract.
In this study, the antioxidant protection of ascorbic acid (AA) supplementation during different unfed periods (24, 48, 120 h) was determined with blood lipid peroxidation level (thiobarbituric acid reactive substances, TBARS) and compared with plasma antioxidant sulfydryl group (RSH) content. Weight loss was induced by increasing the unfed period together with vitamin C supplementation. Blood AA levels decreased by starvation but increased by vitamin C supplementation. RSH content in plasma also decreased with the unfed period; these decreases became apparent by vitamin C supplementation. TBARS formation increased significantly by AA supplementation in the 120-h starvation period.
The aim of the present study was to investigate the impact of hormonal changes during pregnancy and lactation on the expression of peripheral-type benzodiazepine receptors in platelet membranes. Platelet peripheral benzodiazepine receptor binding characteristics, Hamilton anxiety and depression rating Scores, and progesterone and prolactin (PRL) levels were evaluated during pregnancy and lactation in 17 pregnant women [first (n = 9) and third (n = 8) trimesters], 10 lactating women, and 8 nonpregnant women. A significant decrease (38-41%) in peripheral benzodiazepine receptor density was observed in women during the third trimester of pregnancy when compared to nonpregnant controls and women in their first trimester of pregnancy. The decrease is peripheral benzodiazepine receptors was parallel to the peak in progesterone and PRL secretion. The reduction in peripheral benzodiazepine receptor expression is hormone-dependent and may play a regulatory role geared to prevent pregnancy-related overactivity of the hypothalamic-pituitary-ovarian, hypothalamic-pituitary-adrenal, and hypothalamic-PRL axes.
PURPOSE: We previously demonstrated that aneuploidy-free oocytes may be preselected by testing the first and second polar bodies removed from oocytes following their maturation and fertilization. The present paper describes the results of the application of the method in 659 in vitro fertilization cycles from patients of advanced maternal age. METHODS: Using micromanipulation techniques, 3943 oocytes were tested by polar body sampling and fluorescent on situ hybridization analysis using specific probes for chromosomes 13, 18, and 21. RESULTS: Fluorescent in situ hybridization results were available for 3217 (81.6%) of 3943 oocytes studied, of which 1388 (43.1%) had aneuploidies; 35.7% of the aneuploidies were of first meiotic division origin, and 26.1% of second meiotic division origin. Most errors in the first meiotic division were represented by chromatid malsegregation. The transfer of embryos deriving from 1558 of 1829 aneuploidy-free oocytes in 614 treatment cycles resulted in 131 clinical pregnancies and 88 healthy children born after confirmation of the polar body diagnosis. CONCLUSIONS: Polar body testing of oocytes provides an accurate and reliable approach for prevention of age-related aneuploidies in in vitro fertilization patients of advanced maternal age.