Skin cancer in mice due to very low doses of ante-natal ionizing radiation.
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Biomedical subjects
Publications and source records attributed to N Sinha.
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135 cases of oral cancer have been treated by two fractions per week, and the results are compared with 115 approximately identical cases treated by conventional five days a week schedule with other parameters being identical. Radical irradiation was done by 6000 and 6500 rd in 6--6 1/2 weeks (NSD 1800--1900 ret) and palliative dose was 4500 R/4 weeks (NSD 1532 ret). Tumour regression was found markedly superior by conventional regime in radically irradiated cases but much less superior for palliative treatment. Acute and late reaction as well as tumour control at 1 year was better with daily treatment, more so in cases treated for radical cure, while in palliative treatment, the superiority of daily regime was less marked. Our study provides evidence that only for palliation in advanced cases, radiation therapy by 2 fractions a week can be alternatively used.
A simple technique has been developed for isolating intracellular DNA and its bound proteins from uninfected and phage-infected bacteria. This technique, which utilizes aqueous salt concentrations in the physiological range, is based upon the fact that DNA exists in normal cell lysates in a stiff random coil conformation, and has an unusually large excluded volume to mass ratio. Such stiff coils display a unique combination of low sedimentation coefficient and large Stokes radius, enabling them to be separated rapidly from all other cellular components by successive centrifugal and gel permeation steps. Analysis of this purified intracellular DNA fraction from bacteriophage T4-infected Escherichia coli reveals mainly DNA and protein, with a small amount of RNA also present. Among the major proteins obtained are the DNA-dependent RNA polymerase of the host and the products of T4 genes rIIA, rIIB, and 32 (DNA-"unwinding" protein). Small amounts of the proteins coded by T4 genes 43 (DNA polymerase) and 42 (dCMP hydroxymethylase) have also been identified, in addition to at least 13 other phage-coded proteins of unidentified genes. Much of the phage-coded protein in the complex, including the gene 32 protein, does not exchange readily with the same protein exogenously added in the lysate.
Lead is a well-documented testicular toxicant. The present work was planned to study the occurrence of germ cell death after lead administration. Young growing rats were treated with 5, 10 and 20 mg kg(-1) body weight of lead for 2 weeks. Cell death was assessed by employing in situ TUNEL staining, DNA electrophoresis and morphological examination of the tubules. The results showed that Pb induced significant numbers of germ cells to undergo apoptosis in the seminiferous tubules of rats treated with 20 mg kg(-1) body weight. However, DNA fragmentation was not detected at any of the doses. The level of lead accumulation in the testis increased in a dose-dependent manner.
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Endosulfan induced testicular impairment has been reported in vivo in rats. The present study was conducted to evaluate the cytotoxic effects of endosulfan in vitro employing rat testicular cells in culture, that is Sertoli-germ cell coculture. Cytotoxic changes induced by endosulfan (0, 2, 20, 40, and 80 microM) in mixed cultures of Sertoli and germ cells were seen after 24 and 48 h of treatment. Endosulfan led to an increase in germ cell detachment from the Sertoli cell monolayer in a dose dependent manner. A loss in the viability of detached cells was observed in all treated groups. Substantial leakage of the cytosolic enzyme lactate dehydrogenase was observed in the medium after 24 and 48 h endosulfan treatment at concentrations of 20 to 80 microM. The extent of toxicity was greater after 48 h of treatment.
Contrast-induced nephrotoxicity is an important cause of hospital-acquired acute renal insufficiency. Different modalities have been used to prevent contrast induced-nephrotoxicity namely saline infusion, mannitol, furosemide, calcium channel blockers, atrial natriuretic factor and dopamine infusion with variable success. The possible role of medullary ischaemia mediated by renin angiotensin system in genesis of contrast-induced nephrotoxicity prompted us to investigate the role of captopril (a sulfhydryl group containing angiotensin-converting enzyme inhibitor) in its prevention. Seventy-one patients of diabetes mellitus undergoing coronary angiography were included in the study. Patients randomised to receive captopril, received the drug in a dose of 25 mg thrice a day for three days, starting one hour prior to angiography while the patients in the control group underwent angiography in a routine manner without receiving captopril. Following angiography, patients in the control group developed a significant increase in serum creatinine and blood urea nitrogen levels, as compared to those who received captopril. Contrast-induced nephrotoxicity (i.e. a rise of 0.5 mg/dL in serum creatinine) developed in 29 percent of the control group. Administration of captopril reduced the risk of development of contrast-induced nephrotoxicity by 79 percent. Glomerular filtration rate as measured by Tc DTPA renal scanning prior to and 24-72 hours following angiography demonstrated a mean fall of 9.6 ml/min in the control group while those in the captopril group had a mean increase of 13 ml/min in glomerular filtration rate. We conclude that abnormalities of renal perfusion possibly mediated by renin angiotensin system are responsible for development of contrast-induced nephrotoxicity. Administration of the angiotensin-converting enzyme inhibitor, captopril, offers protection against development of contrast-induced nephrotoxicity.
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BACKGROUND: Pulmonary artery hypertension is a common sequelae of a variety of cardiac and lung diseases. Pathogenesis of primary and secondary pulmonary artery hypertension is still debatable. METHODS AND RESULTS: We studied the serum lipoprotein(a) levels in patients with primary (n=27) and secondary (n=19) pulmonary artery hypertension (Eisenmenger syndrome). The results were compared with age and sex matched controls (n=46). We also studied the frequency of high levels of lipoprotein(a) (> 30 mg/dl) in pulmonary artery hypertension. Mean lipoprotein(a) levels were significantly higher in the pulmonary artery hypertension group compared to age- and sex-matched controls (31.60+/-15.49 mg/dl v. 14.66+/-14.7; p=0.0001). All patients were classified into two groups on the basis of their lipoprotein(a) levels (<30 mg/dl and >30 mg/dl). There was a higher frequency of lipoprotein(a) >30 mg/dl in patients of pulmonary artery hypertension v. controls (52% v. 24%; p= <0.001). Younger age, higher functional class, more severe congestive heart failure, shorter duration of symptoms. and more cases of hemoptysis were observed in the group with lipoprotein(a) >30 mg/dl. CONCLUSIONS: High lipoprotein(a) may be a marker and be associated with a more adverse prognosis in severe pulmonary artery hypertension. Larger prospective studies are needed to establish lipoprotein(a) as a risk factor for the development of pulmonary artery hypertension.
BACKGROUND: Thrombotic occlusion of a prosthetic valve continues to be an uncommon but serious complication. Intravenous thrombolytic therapy has been proposed as an alternative to surgical treatment, but only in critically ill patients. METHODS AND RESULTS: Forty-one consecutive patients presenting with 48 episodes of prosthetic valve thrombosis (44 mitral and 4 aortic) were treated with thrombolytic therapy under serial echocardiographic guidance. There were 14 male and 27 female patients. The anticoagulation status was inadequate in 89.6% of episodes. Atrial fibrillation was present in 47.9% of episodes. The prostheses involved in these episodes were tilting disc in 45, bileaflet in 2, and ball and cage type in 1. The Sorin prosthetic valve was the most commonly involved. The time interval between valve replacement and thrombosis ranged from 1 month to 108 months (mean 20.4+/-20.6 months). Patients were in New York Heart Association functional class III in 47.9% and in class II in 43.9% of episodes. Thrombolytic agents used were streptokinase and urokinase in 44 and 4 episodes, respectively. The mean duration of thrombolytic therapy was 27.9+/-15.0 hours and the overall success rate was 87.5%. Patients developed peripheral embolism with almost complete recovery in 5 episodes while significant bleeding that required termination of thrombolytic therapy was observed in 2 episodes. Redo valve replacement was done in 3 episodes because these patients did not improve on thrombolytic therapy (all 3 cases were of recurrent prosthetic valve thrombosis and were found to have pannus peroperatively). Three patients died during thrombolytic therapy because of persistent heart failure. Six patients experienced a total of 13 epidoses of recurrent prosthetic valve thrombosis including index episodes (rethrombosis in 5, re-rethrombosis in 1). They were treated with repeated thrombolysis with a success rate of 76.92%. The mean duration of thrombolytic therapy in these episodes was 36.1+/-14.0 hours. CONCLUSIONS: In patients with prosthetic valve thrombosis, intravenous thrombolysis guided by echocardiography is a safe and effective method that may expand the indications for nonsurgical treatment of prosthetic valve thrombosis. By using serial echocardiography, the duration of thrombolytic therapy can be tailored to the patient's requirement for normalization of valve hemodynamics.
BACKGROUND: Coronary artery disease (CAD) is associated with a higher incidence of allograft failure and mortality in patients with end-stage renal disease (ESRD) following renal transplant. AIM: To evaluate the efficacy of using carotid intimal medial thickness (CIMT) to predict the presence of CAD in patients with ESRD, using coronary angiography (CAG) as the gold standard. MATERIALS AND METHODS: This prospective study enrolled consecutive patients with ESRD who underwent CAG as a part of pretransplant evaluation to rule out the presence of atherosclerotic CAD. An operator who was blinded with respect to the results of the CAG, measured carotid IMT in all patients prior to CAG and recorded it on videotape. Two independent observers blinded to the results of CAG measured carotid IMT offline to validate its predictive accuracy as a noninvasive test in predicting the presence or absence of CAD. Measurement of carotid IMT was done on USG B mode 7.5 MHZ probe [HP 5500 andover, Massachusetts]. Student's t-test was used for inter-group comparisons. Pearson correlation coefficient test was used to assess the relation between CAD and various risk factors and carotid IMT. Linear regression analysis was applied to identify independent factors determining presence of CAD. A P value < 0.05 was considered statistically significant. RESULTS: Mean CIMT was significantly higher in those with CAD as compared to those without [0.80+/- 0.06 vs.0.70+/-0.06 mm, P< 0.0001). Patients with CIMT> 0.75 mm were older and had more incidence of diabetes(78% vs. 47%; P=0.001). Only 4/53 (7%) of patients with CIMT< 0.75 mm had CAD, vs. 38/52 (73%) in those with CIMT >0.75 mm. The sensitivity and specificity of using CIMT > 0.75 as a predictor of CAD was 90.47%and 73% and its positive and negative predictive values were 0.73 and 0.92. On multivariate analysis, only CIMT was a significant predictor of CAD. CONCLUSION: Carotid IMT can be used to predict CAD in patients with ESRD. In the absence of other risk factors,patients with IMT< 0.75 mm may not need a pretransplant CAG.
Twenty patients of isolated mitral stenosis in normal sinus rhythm (age 22 +/- 4 yrs) in whom symptoms of systemic and pulmonary congestion were controlled on diuretics were the subjects of the present study. The effects of addition of Metoprolol 50 mg po bid for 4 weeks on subjective and objective indices of exercise tolerance were evaluated. Metoprolol produced greater than 50% subjective improvement in 80% of these patients. The increase in time to dyspnoea and total work done on treadmill after 90-120 mins, and after 12 hrs of a dose of metoprolol, were both significant (p less than 0.01). In none of the patients, resting heart rate less than 50/mt, resting and exercise systolic BP less than 90 and less than 105 mmHg, respectively, or any important untoward effects were observed. Metoprolol's beneficial effects and safety can be judged in these patients at two hours after first dose in out patients clinic.
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