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Biomedical subjects

P L Wahi

Publications and source records attributed to P L Wahi.

At least 19 recordsLinked to original sources

Active infective endocarditis observed in an Indian hospital 1981-1991.

Clinical data from 186 patients (133 males and 53 females) with 190 episodes of infective endocarditis (IE) occurring between January 1981 and July 1991 were studied retrospectively at a large referral hospital in Northern India with the intention of highlighting certain essential differences from those reported in the West. The mean age was much lower (25 +/- SD 12 years, range 2 to 75 years). Rheumatic heart disease was the most frequent underlying heart lesion accounting for 79 patients (42%). This was followed by congenital heart disease in 62 (33%) and normal valve endocarditis in 17 (9%). Twenty-four patients had either aortic regurgitation (n = 15) or mitral regurgitation (n = 9) of uncertain etiology. Prosthetic valve infection and mitral valve prolapse were present in only 2 patients each. A definite predisposing factor could be identified in only 28 patients (15%). Postabortal sepsis and sepsis related to childbirth accounted for 6 and 5 cases, respectively. Only 1 patient had history of intravenous drug abuse. Two-dimensional echocardiography showed vegetations in 121 patients (64%). Blood cultures were positive in only 87 (47%), with a total of 90 microbial isolates. Commonest infecting organisms were staphylococci (37 cases) and streptococci (34 cases). Except for a significantly higher number of patients with neurologic complications in the culture-negative group, there were no differences between patients with culture-positive and culture-negative IE. Of the 190 episodes of IE, the patients had received antibiotics before admission in 110 (58%) instances. A significantly greater number of culture-negative patients had received antibiotics than did culture-positive patients (87 vs 23, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Frequency of D8/17 B lymphocyte alloantigen in north Indian patients with rheumatic heart disease.

Ninety patients with rheumatic heart disease and 50 age- and sex-matched healthy human volunteers representing a North Indian population were typed for the B cell alloantigen D8/17 using a monoclonal antibody and a single step immunofluorescence technique. This alloantigen was expressed in 66.44% patients with RHD as compared with 14% of the normal population. A high relative risk (RR = 11.13) indicated a strong association of D8/17 B cell alloantigen with rheumatic heart disease. Increase in the frequency of the marker was observed with increasing age up to the fifth decade (40-49 years) in these patients. However, the frequency of this alloantigen, in the present study, in North Indian patients with rheumatic heart disease is lower than that reported in the American population.

Adolescent

Adherence of Streptococcus pyogenes M type 5 to pharyngeal and buccal cells of patients with rheumatic fever and rheumatic heart disease during a one-year follow-up.

In vitro adherence of Streptococcus pyogenes M type 5 to isolated pharyngeal and buccal epithelial cells was studied in patients with acute recurrent rheumatic fever (n = 21), chronic rheumatic heart disease (n = 33), streptococcal pharyngitis (n = 12), and in normal controls. Patients were investigated at admission and one, six and 12 months later. Streptococci adhered significantly more to the pharyngeal cells of patients with rheumatic fever and rheumatic heart disease than to the pharyngeal cells of controls. Adherence of streptococci to pharyngeal cells of patients with pharyngitis was not different from age-matched controls. The adherence of streptococci to the pharyngeal cells of patients with acute rheumatic fever fell during follow-up but even after one year remained significantly higher than in the control group. These findings suggest that host factor(s) controlling streptococcal adhesion and colonization at the pharyngeal mucosa may be important in the pathogenesis of acute rheumatic fever.

Acute Disease

Pathogenesis of congestive state in chronic obstructive pulmonary disease. Studies of body water and sodium, renal function, hemodynamics, and plasma hormones during edema and after recovery.

BACKGROUND: The pathogenesis of salt and water accumulation in patients with chronic obstructive pulmonary disease is unclear and may differ from that in patients with congestive heart failure due to myocardial disease. This study was undertaken to investigate some of the mechanisms involved. METHODS AND RESULTS: Hemodynamics, water and electrolyte spaces, renal function, and plasma hormone concentrations were measured in nine patients with edema due to chronic obstructive pulmonary disease and in six patients after recovery. Mean cardiac output (3.8 +/- 0.26 l/min.m2) was normal, but right atrial (11 +/- 1 mm Hg) and mean pulmonary arterial (41 +/- 3 mm Hg) pressures were increased. Mean pulmonary arterial wedge pressure (11 +/- 1 mm Hg) was normal. Pulmonary vascular resistance (8.6 +/- 1.3 mm Hg.min.m2/l) was increased, but systemic vascular resistance (19.3 +/- 1.3 mm Hg.min.m2/l) and mean arterial pressure (83 +/- 4 mm Hg) were low. All patients were hypoxemic (PaO2, 40 +/- 2 mm Hg) and hypercapnic (PaCO2, 60 +/- 2 mm Hg). There was a significant increase in total body water (+21%), extracellular volume (+45%), plasma volume (+45%), blood volume (+88%), and exchangeable sodium (+38.2%). Renal plasma flow was severely reduced (-63.2%), but glomerular filtration rate was only mildly decreased (-32%). Significant increases were seen in plasma norepinephrine (3.5-fold normal), renin activity (7.6-fold normal), vasopressin (twice normal), atrial natriuretic peptide (9.4-fold normal), growth hormone (10.7-fold normal), and cortisol (1.9-fold normal). After recovery, the PaO2 increased (50 +/- 3 mm Hg) and PaCO2 fell (45 +/- 4 mm Hg), and the patients became free from edema. All the body compartments returned toward normal, although they did not entirely reach normal values. Renal plasma flow increased significantly, and glomerular filtration became normal. Right atrial and pulmonary arterial pressures and pulmonary vascular resistance decreased (p less than 0.01). Cardiac output decreased but not significantly. Blood pressure increased but not significantly. However, systemic vascular resistance increased significantly to a normal value. CONCLUSIONS: We conclude that patients with edema due to chronic obstructive pulmonary disease have severe retention of salt and water, reduction in renal blood flow and glomerular filtration, and neurohormonal activation similar to that seen in patients with edema due to myocardial disease. However, unlike the latter, in chronic obstructive pulmonary disease cardiac output is normal, and systemic vascular resistance and arterial blood pressure are low. This probably is due to the vasodilator properties of hypercapnia. The consequent low arterial blood pressure may be the stimulus for the neurohormonal activation and retention of salt and water.

Adult

Participation of health workers, school teachers and pupils in the control of rheumatic fever: evaluation of a training programme.

In a rural community block of north India we initiated a programme for control of rheumatic fever and rheumatic heart disease (RF/RHD). This included a training campaign for all 74 health workers, 773 school teachers and 12,500 older pupils (class V to X) to enable them to suspect and refer cases of RF/RHD and counsel them about secondary prophylaxis. Training material was used by project staff, medical officers and teachers to convey that this serious disease with onset between 5 and 15 years can be recognized by four simple criteria: fever with joint pain or swelling; breathlessness and fatigue; involuntary face and limb movements. One year later we evaluated awareness generated by training by administering a questionnaire to random samples in the intervention area and in a noncontiguous control area. Health workers, teachers and pupils of the intervention block were significantly better aware of the nature, severity and presentation of the disease and reported having recognized cases whom they had referred for diagnosis, prophylaxis and counselled for follow up. We conclude that a training protocol incorporating simple messages can effectively create practical awareness for RF/RHD control among teachers, health workers and pupils in a rural community.

Community Health Workers

Blood pressure in schoolchildren in northwest India.

Blood pressure was determined among 2,453 schoolchildren aged between 7 and 16 years in the northwest Indian town of Chandigarh to establish the norms. The percentiles were calculated for each age group in both sexes. Both systolic and diastolic blood pressure had a positive correlation with age, weight, height, and body surface area (r = 0.112-0.178, p less than 0.01). There was no difference in the systolic and diastolic pressures of boys compared with girls of corresponding age. The upper limits of normal (90th percentile) systolic/diastolic pressure were 113/74, 119/76, and 126/79 in children aged 7-9 years, children aged 10-12 years, and adolescents aged 13-16 years, respectively. The lower limits of hypertension (95th percentile) for systolic/diastolic pressure were 119/80, 124/81, and 132/82 in each of these groups, respectively. The 99th percentile values indicative of severe hypertension for systolic/diastolic pressure in these groups were 128/88, 135/88, and 149/89, respectively. The 90th percentile of height and weight shown in the percentile table should be taken into consideration whenever blood pressure exceeds the 90th percentile for age and sex while planning the management of an individual.

Adolescent

Effects of prolonged infusion of human alpha calcitonin gene-related peptide on hemodynamics, renal blood flow and hormone levels in congestive heart failure.

We have previously demonstrated that short-term infusion of calcitonin gene-related peptide (CGRP) has beneficial effects in congestive heart failure. The effects of prolonged infusion of CGRP on hemodynamic functions, plasma hormones and renal blood flow were studied in 9 patients with congestive heart failure (New York Heart Association class III or IV, ejection fraction less than 35%). Hemodynamic variables were measured at 30-minute intervals for 8 hours during CGRP infusion (8 ng/kg/min) and for 2 hours after discontinuation. CGRP caused a decrease in right atrial (28%, p less than 0.05), pulmonary artery (22%, p less than 0.02), pulmonary artery wedge (37%, p less than 0.001) and systemic arterial (18%, p less than 0.05) pressures. Systemic vascular resistance decreased more than pulmonary vascular resistance. Cardiac output (72%, p less than 0.001) and stroke volume (60%, p less than 0.02) increased. Heart rate did not change. There was no evidence of tolerance throughout the infusion. The hemodynamic effects were lost within 30 minutes of stopping CGRP. Renal blood flow (34%, p less than 0.01) and glomerular filtration rate (43%, p less than 0.01) increased. Atrial natriuretic peptide decreased (p less than 0.05), while plasma cortisol (p less than 0.02) increased. Plasma epinephrine, norepinephrine, renin activity, aldosterone and growth hormone were unchanged. It is concluded that in patients with severe congestive heart failure, CGRP has sustained beneficial effects on hemodynamic functions and has no adverse effects on hormones. Unlike many other vasodilators, CGRP also increases renal blood flow and glomerular filtration.

Calcitonin Gene-Related Peptide

Profile of right-sided endocarditis: an Indian experience.

The clinical profile of right-sided infective endocarditis in India was studied from a review of records of patients with infective endocarditis admitted to this hospital. From November 1982 to November 1989, 109 patients with infective endocarditis showed vegetations on cross-sectional echocardiography confirming the diagnosis of infective endocarditis. In 19 (17.4%) patients, only the right side of the heart was involved: specifically the tricuspid valve alone in 10; tricuspid and pulmonary valves in 4; tricuspid valve and right ventricular outflow tract in 1; tricuspid valve and right ventricular free wall in 1; pulmonary valve alone in 2; and bifurcation of pulmonary trunk in 1. Eleven patients (57.9%) had underlying congenital heart disease whereas the remaining 8 patients (42.1%) did not have any underlying heart disease. The latter group, therefore, had isolated right-sided infective endocarditis. Previous illnesses leading to isolated right-sided infective endocarditis were: puerperal sepsis in 4; septic abortion in 1; staphylococcal pneumonia in 2; and epididymoorchitis in one. Eight out of 11 patients with congenital heart disease did not report any previous illness. In the remaining 3, right-sided endocarditis followed cardiac surgery in one; dental extraction without prophylaxis in one; and pulmonary balloon valvoplasty in one. All patients with isolated right-sided infective endocarditis had features of septicaemia, but a murmur of tricuspid regurgitation was audible in only 4 (50%) of them. We conclude that, unlike western reports, the pattern of right-sided infective endocarditis in India is different. No drug addict with right-sided infective endocarditis was seen; puerperal sepsis and septic abortion were the commonest causes of isolated right-sided infective endocarditis.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Septic

Cardiovascular and hormonal effects of calcitonin gene-related peptide in congestive heart failure.

The effects of infusing human alpha-calcitonin gene-related peptide were studied in eight patients with congestive heart failure, five normal rabbits and five rabbits with adriamycin-induced cardiomyopathy. In patients with heart failure, calcitonin gene-related peptide caused a dose-dependent increase in cardiac output and decrease in pulmonary and systemic vascular resistance and pulmonary artery pressure. The systemic blood pressure and right atrial and pulmonary wedge pressures decreased only at the highest infusion rate (16 ng/kg per min). Heart rate remained unchanged. Plasma epinephrine increased (p less than 0.05), whereas aldosterone, atrial natriuretic peptide and prolactin concentrations decreased (p less than 0.05). Plasma norepinephrine, renin activity, cortisol and growth hormone concentrations remained unchanged. In both groups of rabbits, the drug decreased blood pressure and increased cardiac output and heart rate. There was a significant increase in renal blood flow (p less than 0.05). The peptide did not affect the contraction amplitude of human and rabbit ventricular myocytes. These findings suggest that calcitonin gene-related peptide is a vasodilator in the rabbit and humans with little direct effect on ventricular myocardium. This peptide may be useful in some forms of heart failure.

Adult

Nifedipine affects neutrophil functions by a non-calcium-mediated mechanism.

Cardiac disorders are known to be associated with neutrophil infiltration. The central role of calcium in modulating neutrophil functions prompted us to examine whether Ca2+ channel blockers could affect vital neutrophil functions in mice. In vitro exposure of mice neutrophil to nifedipine resulted in inhibition of superoxide production in a dose-dependent manner. However, the inhibition of calcium uptake elicited by nifedipine did not appear to account for the observed effect since the extracellular Ca2+ enrichment and depletion did not produce a significant reversal of inhibition. In addition, there was significant inhibition (P less than 0.01) of nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase activity. Cytosolic-free Ca2+, as measured by Quin-2AM fluorescence, showed no significant change indicating that the effect was independent of inhibition of Ca2+ influx. The hypothesis was substantiated by loss of neutrophilic functions following long-term administration of nifedipine. Our data indicate that nifedipine impairs neutrophil functions and support the hypothesis that Ca2+ antagonists also affect cellular functions by non Ca2+ mediated processes.

Animals

Release of oxygen free radicals by macrophages and neutrophils in patients with rheumatic fever.

The generation of oxygen free radicals (OFR) by peripheral blood monocytes and neutrophils of patients with rheumatic fever (RF) and rheumatic heart disease (RHD) has been studied using the luminol-enhanced chemiluminescence technique. The mechanism of OFR generation was studied by measuring NADPH oxidase enzyme activity. The effect of substrate was studied by measuring the hexose monophosphate (HMP) shunt enzymes: glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. Three groups of patients [i) recurrent rheumatic activity, (ii) chronic RHD, (iii) acute pharyngitis) and normal controls were studied at day 0 and followed-up serially at 15, 90 and 180 days. The release of OFR, was significantly higher (P less than 0.001) in patients with recurrent rheumatic activity than in those with acute pharyngitis or chronic RHD, throughout the study period. A significant decline (P less than 0.001) in OFR release was observed from day 0 to day 180 in these patients, whereas no such change was observed in the chronic RHD group. This study raises the possibility that these phagocytic cells, which infiltrate the myocardium, may through generation of OFR, have a role in the pathogenesis of cardiac damage seen in patients with RHD.

Free Radicals

Surface hydrophobicity of "rheumatogenic" and "nephritogenic" strains of group A streptococci and the ultrastructural surface feature of pharyngeal cells exposed to group A streptococci.

The present study was carried out to determine the surface hydrophobicity of group A streptococcal strains responsible for rheumatic fever (RF), "rheumatogenic" strains (RG strains) and strains causing glomerulonephritis, "nephritogenic" strains (NG strains) in relation to their adhesion to human pharyngeal cells. Scanning electronmicroscopic (SEM) studies were carried out to the difference, if any, in the adherence of group A streptococci (M type 5) to pharyngeal and buccal cells (PEC and BEC). By employing two techniques for hydrophobicity determination, salt aggregation titre (SAT) and n-hexadecane binding technique, it was observed that RG strains (M5, M1 and M6) were more hydrophobic than NG strain, M49. However, NG strain M12 was almost equally as hydrophobic as RG strains. The adherence of RG strains, except M1 and M24, to PEC was greater in number than that of NG strains. Although M1 strain was hydrophobic, its adherence to PEC was less. Pepsin and trypsin treatment with streptococci reduced the hydrophobicity and adherence of RG and NG strains to PEC. SEM studies revealed firmly adhered indigenous bacteria on PEC and BEC. Streptococci (M5) adhered more to PEC than to BEC. SEM studies also showed that PEC had a peculiar ultrastructural surface feature to which streptococci adhered. These findings suggest that streptococcal hydrophobicity alone does not determine their adhesion to PEC. The surface nature of PEC might be a characteristic feature of the epithelial cells that allows streptococci to adhere and colonize or it might be a consequence of streptococcal adhesion.

Alkanes

Pathogenesis of edema in constrictive pericarditis. Studies of body water and sodium, renal function, hemodynamics, and plasma hormones before and after pericardiectomy.

BACKGROUND: The pathogenesis of sodium and water accumulation in chronic constrictive pericarditis is not well understood and may differ from that in patients with chronic congestive heart failure due to myocardial disease. This study was undertaken to investigate some of the mechanisms. METHODS AND RESULTS: Using standard techniques, the hemodynamics, water and electrolyte spaces, renal function, and plasma concentrations of hormones were measured in 16 patients with untreated constrictive pericarditis and were measured again in eight patients after pericardiectomy. The average hemodynamic measurements were as follows: cardiac output, 1.98 l/min/m2; right atrial pressure, 22.9 mm Hg; pulmonary wedge pressure, 24.2 mm Hg; and mean pulmonary artery pressure 30.2 mm Hg. The systemic and pulmonary vascular resistances (36.3 +/- 2.5 and 3.2 +/- 0.3 mm Hg.min.m2/l, respectively) were increased. Significant increases occurred in total body water (36%), extracellular volume (81%), plasma volume (53%), and exchangeable sodium (63%). The renal plasma flow was only moderately decreased (49%), and the glomerular filtration rate was normal. Significant increases also occurred in plasma concentrations of norepinephrine (3.6 times normal), renin activity (7.2 time normal), aldosterone (3.4 times normal), cortisol (1.4 times normal), growth hormone (21.8 times normal), and atrial natriuretic peptide (5 times normal). The ratio of left atrial to aortic diameter measured by echocardiography was only minimally increased (1.29 +/- 0.04), indicating that in constrictive pericarditis the atria are prevented from expanding. The studies repeated after pericardiectomy in the eight patients showed that all measurements returned toward normal. CONCLUSIONS: The restricted distensibility of the atria, in constrictive pericarditis, limits the secretion of atrial natriuretic factor and, thus, reduces its natriuretic and diuretic effects. This results in retention of water and sodium greater than that occurring in patients with edema from myocardial disease. The arterial pressure is maintained more by the expansion of the blood volume than by an increase in the peripheral vascular resistance.

Adult

Controlled clinical trial of nifedipine alone and in combination with dilazep in patients with angina pectoris.

The present study was performed to see if the combined treatment with nifedipine and dilazep offers any advantage over monotherapy with nifedipine alone in angina of effort. Thirty-three patients out of 40 with classical stable angina of effort completed this double-blind, randomized, parallel design comparative clinical trial. Both nifedipine alone (15-60 mg) and in combination with dilazep (50 mg) three times a day produced a significant reduction in angina attacks, consumption of nitroglycerin tablets and increased exercise tolerance. There was, however, no difference in the reduction in these parameters between the two groups. There was no significant reduction in blood pressure both systolic as well as diastolic and rate pressure product both when nifedipine was given alone and when it was given in combination with dilazep. Laboratory data did not reveal any dysfunction of liver, kidney and hemopoietic system. The results obtained show that there was no beneficial effect of adding dilazep to nifedipine therapy in the treatment of angina pectoris.

Angina Pectoris

Neutrophil oxygen free radical production proportionates with the degree of myocardial ischemia.

OBJECTIVE: To assess the production of oxygen free radicals by chemiluminescence and to assess leukocyte aggregation, in patients with acute myocardial infarction and angina pectoris, and to compare these to creatine kinase-MB levels. DESIGN: Prospective study with serial estimation at presentation and 72 h later. SETTING: Referral, tertiary care hospital. PATIENTS: Group 1, acute myocardial infarction (n = 18); group 2, stable angina pectoris (n = 8); and age-and sex-matched normal healthy persons (n = 12). All patients included had pain of less than 24 h duration with typical electrocardiographic and laboratory abnormalities. Patients or controls who had any inflammatory disease in the preceding two weeks or who were on anti-inflammatory drugs, calcium channel or beta-adrenoceptor blockers, were excluded. TESTS: Venous blood samples taken at presentation and 72 h later were analyzed for creatine kinase-MB using a standard kit, neutrophilic chemiluminescence and leukocyte aggregation. MAIN RESULTS: In group 1 there were significant rises in both creatine kinase-MB and chemiluminescence, which subsequently regressed (P less than 0.02). There was, however, no statistical correlation between the two. The qualitative pattern of the rise and fall of chemiluminescence was similar in group 2. Changes in leukergy in both groups were not significant. CONCLUSIONS: Oxygen free radical generation occurs early in myocardial ischemia with regression by 72 h. Neutrophilic chemiluminescence may provide an alternative method for assessment of myocardial ischemia.

Cell Aggregation

NADPH oxidase activity in the monocytes and neutrophils of patients with rheumatic fever.

The enzyme NADPH oxidase is involved in the production of oxygen free radicals. We measured its activity in neutrophils and monocytes obtained from patients with acute rheumatic fever, chronic rheumatic heart disease, acute streptococcal pharyngitis and normal controls. Follow up studies were made at 15 days, 3 months and 6 months. Streptococcal membrane antigen, carbohydrate antigens and latex were used to stimulate the oxidative activity in the neutrophils and monocytes. These three agents caused a significant increase in the enzyme activity of the phagocytes of patients with acute rheumatic fever and chronic rheumatic heart disease (p less than 0.001) but not in acute pharyngitis. Maximal NADPH oxidase enzyme activity was observed in patients with acute rheumatic fever. During the follow-up, there was a significant decline in the enzymatic activity in patients with acute rheumatic fever but not in those with chronic rheumatic heart disease. Enzymatic activity was greater when the phagocytic cells were triggered with membrane as compared to carbohydrate antigen and latex in all the groups and at all intervals. The enzymatic response of neutrophils and monocytes was similar although the magnitude of the NADPH oxidase activity was significantly higher in neutrophils than in monocytes.

Adult

Nifedipine administration impairs natural resistance of mice to Salmonella typhimurium.

Administration of Ca2+ channel blockers in cardiac disorders and the central role of Ca2+ in modulating neutrophil functions, prompted us to investigate whether administration of nifedipine to mice would alter their natural resistance to infectious agents like Salmonella typhimurium. Neutrophil chemiluminescence (CL) in response to S. typhimurium was significantly (p less than 0.01) decreased in mice fed with nifedipine (0.015 mg/kg body weight) over a period of six months. Intracellular killing of S. typhimurium by isolated neutrophils also decreased significantly (p less than 0.01) and exponentially with nifedipine administration, representing a 42% fall at six months. In addition the drug administration lowered the survival rate of animals following challenge by a lethal dose of S. typhimurium (LD50 = 1 x 10(4) bacteria/animal). Our data suggest that long term administration of nifedipine lowers the natural resistance of mice to S. typhimurium owing to impaired neutrophil functions.

Animals