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Biomedical subjects

R Nair

Publications and source records attributed to R Nair.

At least 19 recordsLinked to original sources

Cross-challenge studies in rhesus monkeys employing different Indian isolates of hepatitis E virus.

The aim of this study was to determine if rhesus monkeys infected with one isolate of hepatitis E virus (HEV) were immune to subsequent challenge with other isolates of the virus. Three epidemic and one sporadic Indian HEV isolates were employed in the study. The interval between primary inoculation and challenge varied from 1 year and 6 months to 2 years and 9 months. Evidence of HEV infection was ascertained by rise in serum alanine transaminase (ALT) levels and/or seroconversion to antibodies to HEV (anti-HEV), and the presence of HEV-RNA in the bile or faeces of the infected monkeys. No evidence for multiplication of virus in monkeys challenged with different HEV isolates was obtained. These results show that immunity generated by one isolate of HEV protects against different isolates of hepatitis E virus.

Adult

Epididymal fat depot lipoprotein lipase activity is lower in animals with high endogenous fat preferences.

Adipose tissue lipoprotein lipase (LPL) is a key enzyme responsible for the clearance of circulating triglycerides and has been linked to certain pathologic states such as obesity. In order to investigate whether an animal's endogenous fat-preference is associated with differences in adipose tissue LPL, we measured enzyme activity in epididymal fat from high- and low-fat preferring rats. Utilizing a 24h ad libitum feeding paradigm, four groups of outbred adult male Sprague-Dawley rats were screened separately for their macronutrient preferences. Animals exhibiting high- or low-fat preferences were identified and placed back on standard chow. LPL activity was measured in epididymal fat under chow fed or fasted conditions. Epididymal fat LPL activity was significantly less in the high-fat-preferring animals relative to the low-fat-preferring, in both the standard chow-fed state (p = 0.014) and fasted (p = 0.0007) state. LPL activity in heart ventricle and brown adipose tissue was also measured from the same animals. Activity in heart ventricle and brown adipose tissue was significantly lower in the high-fat-preferring group as compared with the low-fat-preferring only following a 24h fast (p = 0.0012 for heart and p = 0.0085 for brown adipose, high- versus low-fat preferring). The data indicate that differences in tissue LPL activity exist between animals with inherent differences in fat preference. Future comparative studies between the two groups of fat-preferring animals could lead to important clues to the regulation of the LPL.

Animals

Pediatric germ cell tumor. An experience with BEP.

PURPOSE: This study is an analysis of our experience with bleomycin, etoposide, and cisplatin (BEP) chemotherapy, in pediatric germ cell tumors (GCTs). PATIENTS AND METHODS: The study included all children (age < 16 years) who were registered between May 1988 and May 1993 with a histologically confirmed diagnosis of GCT and received BEP chemotherapy. In addition to the clinicopathological features, the response rate, survival rate, and toxicity were analyzed. RESULTS: There was a total of 56 patients, of whom 22 had an ovarian tumor and 17 each had a testicular or an extragonadal tumor. Histologically, endodermal sinus tumor was the most common type (62%). Tumor markers were increased in 89% (50 of 56). Complete responses were observed in 89.1% (49 of 55) and partial responses in 10.9% (6 of 55) of the evaluable patients. Five-year actuarial survival was 83% and progression free survival was 93%. Median follow-up was 18 months. Median survival is not yet reached. The chemotherapy was well tolerated. CONCLUSIONS: From the present report, it is apparent that BEP chemotherapy is very effective and well tolerated in children with GCT. The data probably suggests that conservative surgery, when combined with effective chemotherapy, can result in cure of the majority of children with GCTs.

Adolescent

Malignant germ cell tumors in childhood.

The outlook for patients with germ cell tumors was poor before the advent of effective chemotherapy. In this study the outcome of multiagent chemotherapy in children treated for germ cell tumor is assessed. Between January 1984 and December 1990, 107 patients were diagnosed to have germ cell tumors. Postsurgical therapy was based on tumor site, stage, and histology. Combination chemotherapy was employed in patients with Stages I and II disease with postoperative raised tumor markers and all patients with Stages III and IV. Between 1984-1988, patients received cisplatin, vinblastin, bleomycin, and methotrexate (PVB-M), and thereafter between 1988-1990, they received bleomycin, etoposide, and cisplatin (BEP). Of 34 patients treated with PVB-M and 27 treated with BEP, the complete remission rate was 40% and 85%, respectively, and the overall survival was 30% at 5 years for PVB-M and 80% at 3 years for BEP. We conclude that etoposide with cisplatin is superior to vinblastin with cisplatin in the treatment of advanced germ cell tumors because of greater efficacy, decreased toxicity, and better compliance in children.

Adolescent

Modified MACOP-B chemotherapy for intermediate and high grade non Hodgkins lymphomas.

Combination chemotherapy consisting of methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisolone and bleomycin (MACOP-B) has been extensively used for the treatment of Non Hodgkins Lymphoma. However, different results have been reported. The aim of this study was to assess the feasibility of administration of this regimen on an out patient basis and to confirm the efficacy of MACOP-B. 51 patients with intermediate--and high--grade lymphoma were treated with this regimen in a single institute study. Numerous clinical features predictive of response and disease free survival were analysed. The Median age was 48 years (range 14-77). Diffuse large cell lymphoma was seen in 65%, diffuse small cleaved in 10% and diffuse mixed in 15%. Eight patients (15%) had Stage I disease, 18 (35%) Stage II, 12 (23%) Stage III and 13 (25%) Stage IV. Complete remission was achieved in 65% of the patients. With a median follow up of 18 months, 40% of the patients are alive at 40 months. Sixty percent of the complete responders are disease free at 40 months. Response rates did not differ significantly for age, sex, stage, histology, bone marrow involvement and extranodal disease. However patients with absence of B' symptoms, non bulky disease at presentation and diffuse large cell histology had a higher percentage of complete remission. Hematological toxicity occurred in 90% and was grade IV in 14% patients. Three patients died of sepsis. Severe mucositis occurred in 40% of the patients. In conclusion, while it is possible to give aggressive chemotherapy at the out patient basis in India we failed to confirm the high response rates as originally reported.

Adolescent

Maxillary extragonadal germ cell tumor: a case report.

A single case report of a patient with primary extragonadal endodermal sinus tumor affecting the maxillary region is reported here. The patient was treated with combination chemotherapy consisting of bleomycin, cisplatin and etoposide. The child achieved complete remission and is now disease free for three years.

Antineoplastic Combined Chemotherapy Protocols

The Vineberg procedure revisited: angiographic evaluation and coronary artery bypass surgery in a patient 21 years following bilateral internal mammary artery implantation.

A patient receiving bilateral internal mammary implantation (Vineberg's operation) in 1969 was symptom free for a period of 21 years. In 1990 he developed acute myocardial infarction followed by post-infarction angina. Cardiac catheterization revealed severe left main and three vessel disease and patency of both mammary implants which filled the left anterior descending and circumflex coronary arteries via collaterals. Coronary artery bypass surgery was indicated due to the native coronary artery disease and inability of the internal mammary grafts' blood flow to alleviate symptoms. The patient underwent direct coronary artery bypass grafting utilizing femoral vessels for cannulation and saphenous veins for grafting, while preserving the mammary implants. This unique case attests to the longevity of the internal mammary artery grafts. These grafts, even if directly implanted, can serve as a crucial source of blood to an otherwise severely underperfused myocardium. Strategy and technical aspects of surgical redo in patients who underwent Vineberg's operation are discussed.

Aged

Evaluation of quinapril on regional blood flow and cardiac function in patients with congestive heart failure.

Quinapril, a nonsulfhydryl ACE inhibitor, was evaluated in ten New York Heart Association (NYHA) functional class (FC) II-III CHF patients to determine its effects on regional blood flow [effective renal plasma flow (ERPF), renal blood flow (RBF), renal vascular resistance (RVR), hepatic blood flow (HBF), hepatic vascular resistance (HVR), segmental limb pressure (SLP), creatinine clearance (CRCL)] and cardiac function [left ventricular ejection fraction (LVEF)]. Previous vasodilator therapy was withdrawn 2 weeks before baseline measurements. Stable regimens of digoxin and diuretics were continued throughout the study. ERPF was assessed using p-aminohippurate (PAH), HBF by indocyanine green (ICG) clearance, and LVEF by radionuclide scintography. Segmental limb pressures were measured by Doppler flow detection. Measurements were performed at baseline (B) and after 4 weeks of quinapril therapy (10 mg BID). Quinapril increased renal (P less than 0.05) and hepatic blood flow (P = 0.06) and significantly reduced renal and hepatic vascular resistance. Glomerular filtration rate and left ventricular ejection fraction were unchanged. Mean arterial pressure and brachial segmental pressures decreased without change in heart rate. Noninvasive cardiovascular assessments indicate that quinapril improves regional blood flow while exhibiting no change in left ventricular ejection fraction, in patients with NYHA FC II-III CHF.

Antihypertensive Agents

Amplification and overexpression of epidermal growth factor receptor gene in human oropharyngeal cancer.

The presence of epidermal growth factor receptor (EGF-R) gene was determined in 84 patients with squamous cell carcinoma (SCC) of the oropharyngeal region--a highly prevalent, chewing-tobacco associated malignancy in India, using Southern hybridisation analysis of DNA extracted from primary tumor tissues. We observed a 3- to 8-fold amplification of EGF-R gene in 19/66 (29%) of the SCCs of the oral cavity, and about 30-fold EGF-R amplification in 2/18 (11%) hypopharyngeal cancers. Dot blot analysis of total RNA from several tumour tissues, revealed overexpression of the EGF-R gene in the examined patients, with the EGF-R gene amplified. 4 patients with single copy EGF-R gene, did not exhibit overexpression of the gene. Within our sample set, no correlation was evident between EGF-R gene amplification and clinico-pathological parameters of the malignancy. The amplification and overexpression of the EGF-R gene observed in the primary tumour tissues of 25% (21/84) of the human oropharyngeal cancers, indicate possible involvement of the gene in the pathogenesis of these cancers.

Adult

Thrombotic thrombocytopenic purpura: outcome in 24 patients with renal impairment treated with plasma exchange. Canadian Apheresis Study Group.

The Canadian Apheresis Study Group recently completed a randomized clinical trial involving 102 patients with thrombotic thrombocytopenic purpura (TTP), in which treatment with plasma infusion and treatment with plasma exchange were compared. Thirty-three other patients were ineligible or refused to be randomly assigned in the trial. Of the 33 patients, 24 were assessed as ineligible because they would be unable to tolerate the fluid input that would occur if they were randomly assigned to receive plasma infusion. All 24 patients had oliguria and elevated creatinine and/or blood urea nitrogen level. These 24 patients were treated with acetylsalicyclic acid, dipyridamole, and plasma exchange according to the standardized protocol defined in the trial. Blood for tests of factors possibly involved in the pathogenesis of TTP was drawn before exchange and at intervals during and after exchange. The mean platelet count before exchange was 35.5 x 10(9) per L. In 12 of the 24 patients, the platelet count reached 150 x 10(9) per L or greater by 7 days after the initiation of plasma exchange. Three patients responded partially, in that their platelet count increased to at least twice that at presentation, but remained below 150 x 10(9) per L. One patient died during the first week. Of the eight other patients who experienced treatment failure at the 7-day assessment point, six subsequently responded, four while continuing to receive plasma exchange and two after plasma exchange had been discontinued. Of the 15 patients who either responded fully or responded partially by the end of the first cycle, all survived.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Anomalous septal perforator artery: a source for supportive circulation in severe coronary artery disease--case reports.

Anomalous origin of a septal perforator artery is an infrequent angiographic finding. However, its recognition is important in patients with coronary artery disease in order to avoid misdiagnosis and consequent management mistake. In 2 patients, coronary arteriography demonstrated an anomalous septal perforator artery supplying significant blood flow to a myocardial region previously perfused by a severely obstructed major coronary vessel. It appears that an anomalous septal artery can serve as an important source for supportive circulation in severe coronary artery disease.

Aged

Laparoscopic gastrointestinal surgery.

The growth and scope of laparoscopic gastrointestinal surgery are outstripping the ability of medical journals to print series and reports of experience, and much data remain anectodal and preliminary. Laparoscopic cholecystectomy has become established, although, unfortunately, peroperative cholangiography has not yet become normal practice, despite convincing published evidence that it is likely to reduce the increased number of bile ducts that are damaged by laparoscopic surgeons. Imaging the bile ducts and the overall management of choledocholithiasis need re-evaluation, and the approach will change as more surgeons explore the bile ducts laparoscopically. Laparoscopic hiatal anti-reflux surgery will soon be routine, and a whole range of laparoscopically assisted operations on the oesophagus, colon, and rectum will become commonplace. Operations on the liver remain anecdotal. Throughout this rapid progress, surgeons must not forget the principles of (open) surgical practice, whilst carefully kept registers and regular audit of operations will provide new surgical standards.

Cholecystectomy, Laparoscopic

Chronic myelomonocytic leukaemia (an analysis of fourteen consecutive cases).

Fourteen consecutive cases of chronic myelomonocytic leukaemia aged 6 to 73 (mean 40.5) years were reviewed to define the natural history of the disease and the risk of acute transformation. The common presenting features included anaemia, fever, purpura, and bleeding tendencies. Abnormal karyotypes were seen in 4 of 6 patients subjected to cytogenetic analysis. Low dose cytosine arabinoside achieved complete remission in two and partial remission in one, of the four patients treated with this modality. The mean survival was 5.6 (range 2-12) months and two patients) evolved to acute myeloid leukaemia. The long term survival with the present form of therapy in chronic myelomonocytic leukaemia is poor.

Adolescent

Restriction fragment length polymorphism of the L-myc gene in oral cancer patients.

Restriction fragment length polymorphism (RFLP) of the L-myc gene was examined in DNAs from primary tumour tissues and peripheral blood cells (PBC) of 76 Indian patients with squamous cell carcinoma of the oral cavity, and PBC from 101 normal healthy volunteers. The patients and the normal healthy volunteers were classified into three genetic types according to the polymorphic patterns defined by the two alleles (6.6 kb, S fragment; and 10.0 kb, L fragment). DNA isolated from the PBC of each patient always exhibited the same pattern of L-myc alleles as that observed for the corresponding tumour DNA. However, a striking correlation was found between the RFLP pattern and the stage of differentiation of the tumours, as well as the size of the tumour. Thus, a preponderance of the S fragment was observed in the poor to moderately differentiated tumours and the larger (greater than 4 cm) sized tumours. Further, analysis of L-myc RFLP with the clinical pattern of the malignancy showed no significant correlation with nodal metastasis, TNM staging or recurrence of the tumour. The relative ratios of the three genotypes (L-L, L-S, S-S) in the oral cancer patients were not significantly different from those seen in the healthy Indians, implying no predisposition to oral cancer by either allele. However, our results showed that oral cancer patients with a genotype including an S fragment are more likely to develop a poor to moderately differentiated tumour or a larger tumour than a patient without an S fragment. The L and S alleles were equally distributed in the population, with the frequency of each allele being 0.50, consistent with Hardy-Weinberg's law.

Adult

Elucidation of the nifedipine-quinidine interaction.

Four case reports have been published that document a clinically significant drug interaction between nifedipine and quinidine in patients with left ventricular dysfunction. To define the population at risk and the mechanisms involved in manifestations of this interaction, 12 patients currently treated with quinidine for either ventricular or supraventricular arrhythmias were stratified into two groups based on left ventricular ejection fraction (EF) measurements (group A greater than 35%; group B less than 35%). The interaction was conducted through two phases: oral quinidine (Q) and oral quinidine plus nifedipine (N + Q). Pharmacokinetic modeling of total body clearance (CL) and AUC were assessed for each phase. One patient (group A, 70% EF) exhibited the interaction with a 41% decrease in steady-state serum quinidine concentrations. The patient's AUC and CL were 48.2 micrograms/ml.hr (Q) versus 28.6 micrograms/ml.hr (N + Q) and 94.4 ml/min (Q) versus 159.1 ml/min (N + Q), respectively. There was no difference in AUC or CL between the Q and N + Q phases or between groups A and B for the entire population. The N + Q interaction is not hemodynamically mediated. Clinical consideration of the possibility of this low-frequency interaction should be noted.

Adult