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Biomedical subjects

R Nair

Publications and source records attributed to R Nair.

At least 73 records · Page 4Linked to original sources
PubMed1997

Randomized, double-blind comparison of hirulog versus heparin in patients receiving streptokinase and aspirin for acute myocardial infarction (HERO). Hirulog Early Reperfusion/Occlusion (HERO) Trial Investigators.

BACKGROUND: Thrombolytic therapy improves survival after myocardial infarction through reperfusion of the infarct-related artery. Thrombin generated during thrombolytic administration may reduce the efficacy of thrombolysis. A direct thrombin inhibitor may improve early patency rates. METHODS AND RESULTS: Four hundred twelve patients presenting within 12 hours with ST-segment elevation were given aspirin and streptokinase and randomized in a double-blind manner to receive up to 60 hours of either heparin (5000 U bolus followed by 1000 to 1200 U/h), low-dose hirulog (0.125 mg/kg bolus followed by 0.25 mg x kg(-1) x h(-1) for 12 hours then 0.125 mg x kg(-1) x h(-1)), or high-dose hirulog (0.25 mg/kg bolus followed by 0.5 mg x kg(-1) x h(-1) for 12 hours then 0.25 mg x kg(-1) x h(-1)). The primary outcome was Thrombolysis In Myocardial Infarction trial (TIMI) grade 3 flow of the infarct-related artery at 90 to 120 minutes. TIMI 3 flow was 35% (95% CI, 28% to 44%) with heparin, 46% (95% CI, 38% to 55%) with low-dose hirulog, and 48% (95% CI, 40% to 57%) with high-dose hirulog (heparin versus hirulog, P=.023; heparin versus high-dose hirulog, P=.03). At 48 hours, reocclusion had occurred in 7% of heparin, 5% of low-dose hirulog, and 1% of high-dose hirulog patients (P=NS). By 35 days, death, cardiogenic shock, or reinfarction had occurred in 25 heparin (17.9%), 19 low-dose hirulog (14%), and 17 high-dose hirulog patients (12.5%) (P=NS). Two strokes occurred with heparin, none with low-dose hirulog, and two with high-dose hirulog. Major bleeding (40% from the groin site) occurred in 28% of heparin, 14% of low-dose hirulog, and 19% of high-dose hirulog patients (heparin versus low-dose hirulog, P<.01). CONCLUSIONS: Hirulog was more effective than heparin in producing early patency in patients treated with aspirin and streptokinase without increasing the risk of major bleeding. Direct thrombin inhibition may improve clinical outcome.

Analysis of Variance↗
PubMed1997

Risk analysis of coronary bypass surgery after acute myocardial infarction.

BACKGROUND: Current strategies for management of acute myocardial infarction (MI) include thrombolysis, angioplasty, and coronary bypass surgery singly or in combination. This study was designed to identify contemporary risk factors for coronary bypass surgery among patients in this high-risk group. METHODS: Between June 1992 and December 1995, 1181 consecutive patients underwent isolated coronary bypass surgery. Of these, 316 underwent coronary bypass surgery within 21 days of MI. Mean age was 65 years (range, 33 to 87 years), and 73% were male. There were 166 patients with stable angina (group 1), 107 patients with unstable angina requiring intravenous nitroglycerin for a control of ischemia (group 2), 20 patients with angina requiring intraaortic balloon counterpulsation for stabilization (group 3), and 23 patients with severe postinfarction ischemia complicated by cardiogenic shock (group 4). RESULTS: The overall in-hospital mortality rate was 5.1% (16 of 316), which was higher (p < 0.05) than the 2.5% (22 of 865) among patients undergoing coronary bypass surgery without recent myocardial infarction. Mortality increased with severity of clinical preoperative status and was 1.2% in group 1, 3.7% in group 2, 20.0% in group 3, and 26% in group 4. Serious postoperative morbidity occurred in 7.3% of patients. Multivariate logistic regression analysis identified preoperative intraaortic balloon counterpulsation, left ventricular dysfunction, and renal insufficiency as the only independent correlates of mortality. CONCLUSIONS: Coronary bypass surgery can be safely performed in stable patients at any time after acute MI, with an operative mortality similar to elective surgery. Thus, in this era of medical cost containment, there is no apparent indication for prolonged stabilization attempts that delay surgery.

Adult↗
PubMed1997

SR Ca(2+)-ATPase activity and expression in ventricular myocardium of dogs with heart failure.

The purpose of this study was to examine the activity and expression of sarcoplasmic reticulum (SR) Ca(2+)-ATPase in left ventricular (LV) myocardium of dogs with chronic heart failure (HF). LV and right ventricular (RV) tissue specimens were obtained from six normal (NL) control dogs and six dogs with chronic HF (LV ejection fraction, 23 +/- 2%) produced by multiple sequential intracoronary microembolizations. Thapsigargin-sensitive Ca(2+)-ATPase activity was measured in isolated SR membrane fractions prepared from LV and RV myocardium. Ca(2+)-ATPase expression, using a specific dog myocardium monoclonal antibody, was measured in sodium dodecyl sulfate (SDS) extract prepared from LV and RV myocardium. Ca(2+)-ATPase activity in both ventricles of NL or HF dogs increased with increasing Ca2+ concentration and reached a plateau at 3 microM Ca2+. The maximal velocity (Vmax, mumol Pi released.min-1.mg-1) of Ca(2+)-ATPase activity was significantly lower in LV of HF dogs compared with NL (0.15 +/- 0.01 vs. 0.23 +/- 0.01, P < 0.05), whereas the affinity of the Ca2+ pump for Ca2+ was unchanged. LV tissue levels of Ca(2+)-ATPase (densitometric units/5 micrograms noncollagen protein) were also significantly lower in LV myocardium of HF dogs compared with NL (3.52 +/- 0.43 vs. 5.53 +/- 0.47, P < 0.05). No significant differences in Ca(2+)-ATPase activity or expression were observed in RV myocardium of HF dogs compared with NL. We conclude that SR Ca(2+)-ATPase activity and protein levels are reduced in LV myocardium of dogs with chronic HF. This abnormality of the SR Ca2+ pump of the failed LV can result in impaired Ca2+ uptake and ultimately to Ca2+ overload and global LV dysfunction.

Animals↗
PubMed1996

Pharmacological characterization of alpha 1-adrenoceptors in porcine uterine artery.

This study was undertaken to ascertain if changes in the affinity to alpha 1-adrenoceptor agonists and antagonists could explain the increase in uterine artery vasoconstriction to adrenergic stimuli during the luteal phase of the estrous cycle in pigs. We also sought to determine the subtype(s) of adrenoceptor (alpha 1A and alpha 1B) in the porcine uterine artery. When phenylephrine was the agonist, uterine artery pA2 values for prazosin were 8.98, 9.04 and 9.10 in the luteal and follicular phases and in early pregnancy, respectively. The KA (dissociation constant) values for phenylephrine were 6.5, 3.7 and 4.4 (microM) in the luteal and follicular phases and in early pregnancy, respectively. The use of the putative alpha 1A-adrenoceptor WB4101 (2-[[[2-(2,6-dimethoxyphenoxy)ethyl]amino]methyl]-1,4-benzodioxane ) and the alpha 1B-adrenoceptor antagonist chloroethylclonidine indicated that both alpha 1A- and alpha 1B-adrenoceptors are present in the porcine uterine artery and that a similar magnitude of inhibition of responses to noradrenaline by each of the antagonists occurred in arteries from the luteal and follicular phases and in early pregnancy. This suggests that the alpha 1A:alpha 1B adrenoceptor ratio does not vary significantly during the estrous cycle and in early pregnancy. This study indicates that porcine uterine artery alpha 1-adrenoceptor affinity is similar in the luteal and follicular phases of the estrous cycle and in early pregnancy.

Animals↗
PubMed1996

Increased left ventricular dysfunction in elderly patients despite successful thrombolysis: the GUSTO-I angiographic experience.

OBJECTIVE: This study sought to determine whether the recovery of regional and global left ventricular function is reduced in elderly patients despite successful thrombolytic therapy for acute myocardial infarction. Comparisons were made between elderly (> or = 75 years old, n = 47) and adult (< 75 years old, n = 434) patients enrolled in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) angiographic trial who underwent catheterization at 90 min and 5 to 7 days after thrombolysis and who had an open infarct-related artery with Thrombolysis in Myocardial Infarction (TIMI) grade 2 to 3 flow at both times. BACKGROUND: The morbidity and mortality of acute myocardial infarction is increased in elderly patients, presumably because of multiple adverse coexistent baseline variables. However, functional recovery after thrombolysis has not been characterized in the elderly. METHODS: Ejection fraction, end-systolic volume index, infarct and noninfarct zone contractile function (SD/chord) and infarct extent (number of chords) were determined. RESULTS: At 90 min, elderly patients with an open infarct-related artery had decreased infarct zone contractile function (-2.8 +/- 0.2 vs. -2.3 +/- 0.1 SD/chord in adults, p < or = 0.05) and a greater extent of injury (26.0 +/- 2.6 vs. 20.7 +/- 0.8 chords in adults, p < or = 0.05). At 5- to 7-day follow-up ventriculography, ejection fraction was reduced, and end-systolic volume index was significantly increased in elderly patients compared with adults. The severity of regional wall motion dysfunction in the infarct zone was also greater in the elderly than in adults at 5- to 7-day follow-up (-2.6 +/- 0.2 vs. -1.9 +/- 0.1 SD/chord, respectively, p < or = 0.005). Non-infarct zone contractile function at 90-min ventriculography was similar in both groups. Despite a patent infarct-related artery at 90-min, the 30-day mortality rate in the elderly remained elevated (17.8%) compared with that of adults (4%) (p < or = 0.0001). Elderly patients were predominantly female and had a higher prevalence of hypertension, multivessel coronary disease, previous infarction, anterior infarctions and later time to treatment (between 3 and 6 h) than adults. However, age > or = 75 years remained an independent determinant by multivariable regression analysis of 1-week postinfarction end-systolic volume index, regional left ventricular dysfunction (p = 0.02 and p < or = 0.008, respectively) and 30-day mortality (p < or = 0.0001). CONCLUSIONS: Elderly patients had increased damage in the infarct zone and had persistently increased mortality despite sustained infarct-related artery patency after successful thrombolysis. Although the causes are probably multifactorial, a more rapid progression of ischemic injury or a blunted postreperfusion recovery appears to contribute to the poorer outcomes in elderly patients.

Adult↗
PubMed1996

Intestinal malrotation--experience with 56 patients.

Intestinal malrotation is a common cause of upper gastro-intestinal obstruction and presents with duodenal obstruction caused by volvulus of the midgut loop. Patients are therefore at risk of catastrophic midgut infarction and it is a more frequent cause of duodenal obstruction in infants than duodenal atresia (92% in the neonatal period). Urgent upper contrast studies under surgical supervision are necessary in those patients whose plain films are not diagnostic. Rectal bleeding is an ominous sign, with 78% of patients having gangrenous bowel. Total midgut infarction is incompatible with survival in a Third-World environment.

Female↗
PubMed1996

Ectopic kidney presenting as appendix mass or abscess.

Renal ectopia is very rare and its associated pyelonephritis can simulate an appendix mass/ abscess or colonic tumour which may result in needless surgical exploration, as illustrated by our experience with 3 cases reported in this article. Careful ultrasonography and urinalysis can obviate this confusion and save unnecessary operation.

Female↗
PubMed1996

Low dose cytosine arabinoside in the treatment of myelodysplastic syndrome.

Twenty eight patients of myelodysplastic syndrome (MDS) were treated with low dose cytosine arabinoside to study the effect of this treatment modality. All patients presented with a hemoglobin of less than 12 Gm/dl, 4 (15%) had neutropenia with an absolute neutrophil count of less than 500 x 10(6)/L and 18 (65%) had thrombocytopenia of less than 100 x 10(9)/L. The subtypes according to the bone marrow evaluation included 14 patients of refractory anemia with excess blasts (RAEB), 10 refractory anemia with excess blasts in transformation (RAEB-T), and 4 chronic myelomonocytic leukemia (CMML). Five patients (18%) achieved complete hematological response, 10 (36%) had a partial response and 9 (33%) patients had no response. Four patients died early during treatment due to tumor lysis (1 CMML) and hemorrhage (3 RAEB). Seven patients progressed to acute myeloid leukemia (AML) while on therapy and three progressed to AML after completion of therapy. Five patients died of hemorrhage and 3 of septicaemia after achieving an objective response. The mean duration of follow up in these patient was 8 months (range 1 month-3 years). Only 3 patients of RAEB have survived for greater than 2 years. Our data reveals the short term benefit of this mode of therapy and emphasizes the need to develop newer therapeutic approaches.

Adolescent↗
PubMed1996

Infections in the immunocompromised host: a prospective multicenter survey in patients receiving chemotherapy for acute leukemia.

Patients receiving chemotherapy for acute leukemia were prospectively followed up to determine the frequency, nature and outcome, of episodes of infection during a 6 or 12 month period at each of the participating centres. A total of 605 cycles of chemotherapy were surveyed. Of these, 490 cycles were received by patients with acute lymphoblastic leukemia (ALL) and 115 by patients with acute non-lymphoblastic leukemia (ANLL). 241 episodes of infection were recorded during the survey: 179 among ALL patients and 62 among patients of ANLL. Infections were more common during chemotherapy for ANLL than for ALL, occurring in 54% (62/115) and 36% (179/490) of chemotherapeutic cycle respectively. A favorable response to empiric antibacterial agents was seen in 39% (23/59) of episodes in ANLL patients and 77% (134/174) of episodes among ALL patients. Infection presented as fever of unidentified origin in an overwhelming majority (63%) of episodes. Gastroenteritis and pneumonia occurred with a frequency of 11% and 10% while the frequency of all other diagnoses was 3% or less. Overall, E coli and Candida were the most frequently isolated organisms while Staphylococcus aureus and Group A Streptococci were the most frequent isolates from blood and throat swabs, respectively. A high degree of resistance to commonly used antimicrobial agents was seen among the most frequently isolated organisms. About 75% of episodes of infection which did not respond to antibacterial agents responded to empiric systemic antifungal therapy; although fungi were mycologically isolated in only a quarter of these instances. Oropharyngeal candidiasis occurred in association with 3% of chemotherapeutic cycles.

Humans↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

A tissue-culture model for the study of canine vocal fold fibroblasts.

A tissue-culture model has been developed for the study of fibroblasts from the canine vocal fold. Laryngeal tissue (lamina propria) obtained from euthanized dogs is rinsed, cut into 1-mm3 pieces, and incubated in 5% carbon dioxide at 37 degrees C. A confluent monolayer is established within several days. Detectable levels of elastin in the tissue culture supernatant are measured by an indirect enzyme-linked immunosorbent assay. Various external agents have been shown to affect elastin production. The effects of KTP laser irradiation, hydrocortisone (1.3 mumol/L), transforming growth factor-beta (10 ng/mL), and human leukocyte elastase have been measured. Thus the canine vocal fold fibroblast tissue culture is established as a model for further investigations to improve wound healing and to understand the wound-healing process following laryngeal microsurgery.

Animals↗
PubMed1995

Chromosome investigations & clinical outcome in patients with myelodysplastic syndromes.

A total of 25 patients with primary myelodysplastic syndrome (p-MDS) were cytogenetically investigated. The incidence of abnormal karyotypes was higher, detected in 88 per cent of the patients and the most frequent abnormality was a terminal deletion of chromosome 7 (45% of the patients with abnormal karyotypes) followed by an i (17q) (18%), +21(14%), -5/5q (9%), del (11) (q22) (9%). Cytogenetic analysis after therapy/after leukaemic transformation indicated either stable clones (2 patients) or emergence of new clones such as inv(5) (q32q36), del (17) (p13), +20, +22 (1 patient each). It is to be noted that of the 8 patients with leukaemic transformation, 5 had del (7q). The leukaemic transformation (32% of the patients) was not related to the percentage of abnormal karyotypes not to the percentage of blasts at the time of the MDS presentation. Chromosome instability was shown by 10 (45%) patients. Our data indicate that higher frequency of chromosomal aberrations with involvement of chromosome 7 may be the result of underlying disease.

Adolescent↗
PubMed1994

Regulation of intra- and extracellular pH in the rat brain in acute hypercapnia: a re-appraisal.

Recent results have demonstrated that intracellular pH (pHi) in nerve and glial cells is not regulated back to normal during CO2 exposure if extracellular pH (pHe) is reduced. This raises the question about regulation of pHi and pHe in vivo. In order to successively reduce pHe we exposed animals to incremental increases in CO2 tension (11, 27.5, 42.5%) and studied regulation of pHi during the first 90 min of hypercapnia. Extracellular pH, as well as Na+, K+, and Cl- concentrations, were also measured, as were whole tissue contents of Na+, K+, and Cl-. At all CO2 tensions studied, pHe slowly increased during CO2 exposure. In animals breathing 11% CO2 (delta pHe approximately 0.2 units), pHi increased slowly. However, in animals exposed to 27.5% CO2 or 42.5% CO2 (delta pHe > 0.4 units), no regulation of pHi was observed. Extracellular HCO3- concentrations increased substantially already during the first 15 min of hypercapnia (not significant in animals breathing 42.5% CO2), and then gradually rose. These increases were accompanied by a decrease in Cl- and an increase in Na+ concentration, K+ concentration remaining constant. The total tissue content of these ions remained constant, suggesting that extracellular HCO3- concentration increases by Cl-/HCO3- antiport and/or by Na+.2HCO3- symport, the HCO3- emanating from intracellular sources. The results challenge the dogma of the supremacy of mechanisms regulating pHi, and suggest that brain cells, possibly astrocytes, regulate pHe at the expense of their own pH homeostasis. By inference, we further conclude that regulation of pHi normally occurs only if pHe is first regulated back close to normal value.

Animals↗
PubMed1994

Correlation of intracoronary ultrasound plaque characteristics in atherosclerotic coronary artery disease patients with clinical variables.

It was examined whether intracoronary ultrasound-defined plaque morphology of symptom-producing, severely stenosed, atherosclerotic coronary artery lesions is related to patient-related clinical variables. Data regarding anginal pattern (stable vs unstable), age, sex, history of smoking, diabetes, hypertension, hypercholesterolemia and lesion location were recorded in 146 hemodynamically stable patients referred for clinically indicated balloon angioplasty or directional atherectomy. Intracoronary ultrasound images of the lesions were obtained before and after the intervention. Lesions were classified as soft (homogeneous echoes less dense than adventitia) or hard (bright echoes with or without acoustic shadowing). Eighty-three lesions (57%) were classified as soft and 63 (43%) as hard. Univariate analysis showed anginal pattern, age, vessel location and history of smoking to be significantly related to plaque morphology. Multivariate analysis revealed only anginal pattern, age and vessel location to be independent predictors of plaque morphology. The frequency of echogenic hard plaque was significantly higher in patients aged > 60 years (56 vs 30%; p = 0.001), those with stable angina (69 vs 35%; p = 0.002), and lesions located in the distal arterial segments (68 vs 31%; p < 0.001) than in younger ones, those with unstable angina, and lesions in proximal segments, respectively. Based on previous studies, echogenic hard plaques are likely to be predominantly fibrous or calcific, or both, whereas low-echogenicity soft plaques are likely to be fibrocellular, lipid rich or thrombotic, or a combination. This difference in plaque morphology is probably due to differences in the predominant mechanism of plaque formation (i.e., slow growth vs rupture/thrombosis).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗