Biomedical subjects
Publications and source records attributed to R Rai.
Four hundred and sixty-seven male patients with leprosy were screened for genital involvement. Genital lesions were observed in 6.6% of all male cases of leprosy. They were seen most frequently in lepromatous leprosy (25.8%), followed by borderline lepromatous (13.3%) and borderline tuberculoid (1.4%) leprosy.
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Active site titration by a reversible tight-binding inhibitor normally depends on prior knowledge of the inhibition constant. Conversely, the determination of tight-binding inhibition constants normally requires prior knowledge of the active enzyme concentration. Often, neither of these quantities is known with sufficient accuracy. This paper describes experimental conditions under which both the enzyme active site concentration and the tight-binding inhibition constant can be determined simultaneously from a single dose-response curve. Representative experimental data are shown for the inhibition of human kallikrein.
Saccharomyces cerevisiae selectively uses good nitrogen sources (glutamine) in preference to poor ones (proline) by repressing GATA factor-dependent transcription of the genes needed to transport and catabolize poor nitrogen sources, a physiological process designated nitrogen catabolite repression (NCR). We show that some NCR-sensitive genes (CAN1, DAL5, DUR1,2, and DUR3) produce two transcripts of slightly different sizes. Synthesis of the shorter transcript is NCR-sensitive and that of the longer transcript is not. The longer transcript also predominates in gln3Delta mutants irrespective of the nitrogen source provided. We demonstrate that the longer mRNA species arises through the use of an alternative transcription start site generated by Gln3p-binding sites (GATAAs) being able to act as surrogate TATA elements. The ability of GATAAs to serve as surrogate TATAs, i.e. when synthesis of the shorter, NCR-sensitive transcripts are inhibited, correlates with sequestration of enhanced green fluorescent protein (EGFP)-Gln3p in the cytoplasm in a way that is indistinguishable from that seen with EGFP-Ure2p. However, when the shorter, NCR-sensitive DAL5 transcript predominates, EGFP-Gln3p is nuclear. These data suggest that the mechanism underlying NCR involves the cytoplasmic association of Ure2p with Gln3p, an interaction that prevents Gln3p from reaching it is binding sites upstream of NCR-sensitive genes.
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Advances in radiological and endoscopic techniques have allowed many biliary complications after orthotopic liver transplantation (OLT) to be managed without surgery. The influence of nonsurgical management on the outcome of patients requiring surgical revision has not been addressed. We reviewed our 10-year experience (October 1988 to January 1998) of Roux-en-Y choledochojejunostomy (CDJ) to treat biliary complications after OLT. Forty-six patients underwent CDJ for biliary complications (32 men, 14 women; age, 22 to 65 years; median, 60 years). Biliary reconstruction at the time of OLT was duct to duct in 41 patients, primary CDJ in 3 patients, and gall bladder conduit in 2 patients. T-tubes were used only in patients with gallbladder conduit. The indication for CDJ was biliary leak (23 patients), stricture (20 patients), biliary stones (2 patients), and biliary sludge (1 patient). Two patients (4.3%) had associated hepatic artery thrombosis. The bile leaks were diagnosed at a median of 29 days post-OLT (range, 2 to 65 days) and strictures at a median of 2 years (range, 33 days to 6.5 years) post-OLT. Before surgery, 25 patients (54%) underwent an attempt at radiological or endoscopic therapeutic intervention that failed. Median follow-up was 5 years (range, 9 months to 10 years). Early complications occurred in 12 patients (26%); the most common was chest infection (4 patients). There were 3 perioperative deaths (6%); 1 death was directly related to surgery. Late complications, mainly anastomotic strictures, occurred in 10 patients (22%), half of which were successfully treated by biliary balloon dilatation. The complication rate post-CDJ was less in those who underwent a failed nonsurgical approach than those proceeding straight to surgery (9 of 25 patients; 36% v 13 of 21 patients; 62%; P =.21, not significant). The procedure-related mortality for surgical revision of biliary complications after OLT is low, but early and late complications are common. A failed attempt at nonsurgical management does not increase the complications of reconstructive surgery. Strictures after CDJ should be considered for biliary balloon dilatation.
The obstetric management of women with antiphospholipid (aPL) syndrome remains controversial. Despite recent advances, the controversies have been fueled by our limited understanding of the multi-factorial causes of aPL-associated pregnancy loss and the lack of data from randomized studies. We have escaped from the narrow confines of the concept of aPL pregnancy loss being purely thrombotic in aetiology and attention is now focused on the adverse effects of aPL on embryonic implantation and trophoblast invasion. Combined treatment with aspirin and heparin has been demonstrated in two randomized studies to lead to a high live birth rate in aPL pregnancies. However, successful pregnancies are characterized by a high rate of perinatal complications and some women are refractory to this treatment combination. In addition to addressing these issues, multi-centre studies, which should perhaps be internet based, are needed to identify those aPL that are causative of pregnancy complications and those that are not, the role of IVIG and the long-term follow-up of both mothers with aPL and their babies.
OBJECTIVE: To determine the prevalence of antiphospholipid (aPL) and anti-beta 2 glycoprotein I (anti-beta2-GPI) antibodies in women referred for IVF and to prospectively evaluate the effect of these antibodies on IVF outcome. DESIGN: Prospective observational study. SETTING: A university hospital and IVF unit. PATIENT(S): Three hundred eighty consecutive women referred for IVF. INTERVENTION(S): Blood samples taken before commencement of IVF cycles were tested for the presence of aPL (lupus anticoagulant [LA], anticardiolipin [aCL], and antiphosphatidyl serine antibodies [aPS]) and anti-beta2-GPI antibodies. MAIN OUTCOME MEASURE(S): Antibody prevalence, pregnancy rates, and live birth rates. RESULT(S): Of the total 380 women, 89 tested persistently positive for aPL (23.4%). None of 176 women tested for IgG aPS antibodies had a positive titer. Only 3.3% (11 of 329) tested positive for anti-beta2-GPI antibodies. Pregnancy rate, live birth rate, gestational age at delivery, and birth weight were not affected by aPL status. CONCLUSION(S): Although women referred for IVF have a high prevalence of aPL, these antibodies do not affect the outcome of treatment. Screening women undergoing IVF for aPL is not justified.
INTRODUCTION: The purposes of this study were: 1) to analyze the early results of cadaveric renal transplantation from either hepatitis C virus seropositive (HCV+ ) or hepatitis C virus seronegative (HCV-) donors into HCV + recipients; and 2) to determine whether HCV+ patients with end-stage renal disease (ESRD) might benefit from receiving renal allografts from HCV + donors. METHODS: From January 1997 to June 1999, 28 patients with ESRD and HCV infection underwent 29 cadaveric renal transplants. The data were reviewed retrospectively. Nineteen of the renal transplants were performed with allografts obtained from 15 HCV + donors and 10 with allografts obtained from 10 HCV- donors. The median follow-up was 16.2 months, with an average of 15.4+/-2 months. RESULTS: Recipients of HCV + renal allografts had shorter waiting times for transplantation. On average, patients who received a kidney from HCV + donors were transplanted 9+/-3 months after being placed on the transplant list, compared to 29+/-3 months for patients who received a kidney from a HCV- donor. Shorter waiting times were noted in every blood type group. There were no significant differences in rejection episodes, infectious complications, renal function, liver function, graft survival, or patient survival. CONCLUSIONS: The use of renal allografts from HCV + donors for HCV + recipients shortens the waiting time for these patients, with no short-term differences in renal and liver function, graft loss, or patient survival.
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Human reproduction is extraordinarily wasteful. The reasons for this have taxed all of the contributors to this book. As we move into the 21st century it is sobering to reflect on the fact that we have failed to harness the power of the evolving revolution in molecular medical biology to answer the fundamental question: why is the fate of a fertilized egg so hazardous and so unsuccessful? The following account summarizes our limited knowledge of the epidemiology of miscarriage and then moves on to consider some of the medical causes of miscarriage. The contribution of genetic abnormalities to the problem of pregnancy wastage is discussed elsewhere in this volume.
The hemostatic system plays an important role in three crucial stages of pregnancy: ovulation, implantation, and placentation. A thrombophilic defect is an abnormality in the coagulation pathways that predisposes an individual to thrombosis. Pregnancy is a hypercoaguable state and interest has focused on the potential role that thrombophilic defects may play in the etiology not only of recurrent miscarriage but also of late pregnancy complications. Maternal intervillous blood flow does not develop to any significant extent before 8 weeks of gestation and thrombophilic defects are therefore unlikely to contribute to pregnancy loss before this time. Retrospective studies have reported a similar prevalence of genetic thrombophilic defects among women with recurrent first-trimester miscarriage and controls but an increased prevalence among those with second-trimester miscarriage and later pregnancy complications. There is a paucity of data documenting the prospective outcome of untreated pregnancies among women with thrombophilic defects and of the placental histology in these pregnancies. Until these issues have been addressed, routine thromboprophylaxis during pregnancy cannot be recommended for women with thrombophilic abnormalities.
Recurrent miscarriage and later pregnancy complications are in some cases associated with placental thrombosis and infarction. The aim of this study was to assess the value of low dose aspirin (75 mg daily) in improving the subsequent livebirth rate amongst women with either unexplained recurrent early miscarriage (<13 weeks gestation; n = 805) or unexplained late pregnancy loss (n = 250). Amongst women with recurrent early miscarriages, there was no significant difference in the livebirth rate between those who took aspirin (251/367; 68.4%) compared with those who did not take aspirin [278/438; 63.5%; odds ratio (OR) 1.24; 95% confidence interval (CI) 0.93-1.67]. This relationship was independent of the number of previous early miscarriages. In contrast, women with a previous late miscarriage who took aspirin had a significantly higher livebirth rate (122/189; 64.6%) compared with those who did not take aspirin (30/61; 49.2%: OR 1.88; 95% CI 1.04-3.37). The empirical use of low dose aspirin amongst women with unexplained recurrent early miscarriage is not justified. We are currently investigating the role of incremental doses of aspirin in the treatment of women both with early miscarriages associated with thrombophilic abnormalities and in those with late pregnancy losses.
The prevalence of polycystic ovaries (PCO) was established amongst 2199 consecutive women (median age 33 years; range 19-46) with a history of recurrent miscarriage (median 3; 3-14). A diagnosis of PCO was made if the ovarian volume was enlarged (>9 ml), there were >/=10 cysts of 2-8 mm in diameter in one plane and there was increased density of the stroma. In a cohort study, the prospective pregnancy outcome of 486 of the women scanned who were antiphospholipid antibody negative and who received no pharmacological treatment during their next pregnancy was studied. The prevalence of PCO was 40.7% (895/2199). The livebirth rate was similar amongst women with PCO (60.9%; 142/233) compared to that amongst women with normal ovarian morphology (58.5%; 148/253; not significant). Neither an elevated serum luteinizing hormone concentration (>10 IU/l) nor an elevated serum testosterone concentration (>3 nmol/l) was associated with an increased miscarriage rate. Polycystic ovarian morphology is not predictive of pregnancy loss amongst ovulatory women with recurrent miscarriage conceiving spontaneously. The search for a specific endocrine abnormality that can divide women with PCO into those with a good and those with a poorer prognosis for a future successful pregnancy continues.
The purpose of this study was to determine the prevalence of thyroid antibodies in women with recurrent miscarriage and to observe whether their presence was predictive of future pregnancy outcome. A total of 870 consecutive, non-pregnant women with a history of three or more pregnancy losses and normal parental karyotypes were investigated for the presence of thyroglobulin antibodies (TgAb) and for thyroid microsomal antibodies (TmAb). Thyroid antibodies were found in 162 (19%) women. TgAb only were found in eight women (5%); TmAb only in 98 (60%) and both TgAb and TmAb were found in 56 (35%). Thirteen women had a history of thyroid disease and a further 15 women were found to have abnormal thyroid function. All 28 were excluded from the pregnancy outcome study. Among the remaining 134 thyroid antibody positive women, 36 women were not tested and normal thyroid stimulating hormone results were obtained for 98. In the group proven euthyroid, 14 of 24 untreated pregnancies resulted in live births (58%). Among the 710 thyroid antibody negative women, 47 of 81 untreated pregnancies resulted in live births (58%). The future risk of pregnancy loss in women with unexplained recurrent miscarriage is not affected by their thyroid antibody status.
BACKGROUND: Percutaneous stent placement is an accepted method of palliation in malignant biliary obstruction. Factors predicting early mortality after this procedure have not been identified. METHODS: We performed a retrospective study of 141 patients with malignant biliary obstruction who underwent percutaneous stent placement for biliary decompression to identify the risk factors associated with early mortality (< or = 30 days). RESULTS: Of 14 clinicopathological and laboratory variables analysed blood urea, albumin, haemoglobin and alkaline phosphatase were found to be significant on univariate analysis. The age and gender of the patient along with cancer type, level of obstruction, presence of pyrexia and bilirubin level had no influence on early mortality. Stepwise logistic regression identified the haemoglobin level and blood urea to be independently significant in predicting early mortality. Overall 30-day mortality was 20.5% (29/141). Patients with blood urea over 4.3 mmol/l and a haemoglobin less than 10.9 g/dl had a mortality rate of 52% (12/23) compared with 14% (17/118) in the remainder. Using these two variables a regression equation has been derived which allows calculation of the probability of survival at 30 days after the percutaneous procedure. CONCLUSIONS: Laboratory variables in patients with malignant obstructive jaundice can be used to predict mortality following percutaneous stent insertion.
We define magnetization for a noisy autoassociative neural network driven by an external periodic field. Numerical simulations are carried out to investigate the effect of drive amplitude and frequency and noise strength on the area of the hysteresis loop. We observe that in the presence of weak periodic signal, the network exhibits a maximum in the hysteresis loop area at a nonzero noise intensity indicating maximum synchronization between the periodic signal and the response. It also goes through a maximum as a function of signal frequency.
We have investigated the effect of noise on a simple prey-predator model where the oscillations are triggered by the internal dynamics of the system without the aid of any external periodic drive. We report the occurrence of stochastic resonancelike behavior in this system, which does not have a threshold or a potential barrier, in the absence of an external drive.