Lectin mediated binding of Streptococcus pyogenes to human oropharyngeal mucosal epithelial cells.

The study was carried out to determine the role of lectins and sugars in the adhesion of S. pyogenes to human pharyngeal and buccal epithelial cells. In vitro adhesion assay has shown that Con A and Dolicos biflorus lectins inhibited the attachment of S. pyogenes to the oropharyngeal mucosal cells. Among different sugars used, N-acetyl-D-galactosamine and D-galactose have significantly blocked the binding of streptococci to PEC and BEC. These findings indicate that lectins and sugar molecules mediate the adhesion of S. pyogenes to the pharyngeal epithelial cells which may be important in the cellular pathogenesis of streptococcal infections which originate at the human oropharyngeal mucosa.

Increase in activated T cells and reduction in suppressor/cytotoxic T cells in acute rheumatic fever and active rheumatic heart disease: a longitudinal study.

In a prospective study, patients with acute rheumatic fever (ARF) and active rheumatic heart disease (ARHD) showed a significant increase in CD4+ T cells, CD22+ B cells, and CD4:CD8 cell ratio but a significant decrease in the percentages of CD8+ and CD3+ T lymphocytes compared with patients with quiescent RHD (CRHD) or streptococcal pharyngitis (SP) and normal controls. The proportion of interleukin-2 receptor (IL-2R)+ (CD25+) cells was higher in peripheral blood mononuclear cell cultures (both before and after phytohemagglutinin stimulation) of ARF and ARHD patients than in those of CRHD or SP patients or controls; this finding persisted up to 48 weeks. In ARF patients, the percentage of CD8+ cells returned to within normal range at 48 weeks. Furthermore, the percentage of IL-2R+ cells correlated positively with the percentage of CD4+ but not of CD8+ lymphocytes, suggesting that helper/inducer T cells are in an immunologically activated state and may account for aberrations in the distribution of lymphocyte populations in peripheral blood of ARF and ARHD patients.

Enhancement of IL-1, IL-2 production and IL-2 receptor generation in patients with acute rheumatic fever and active rheumatic heart disease; a prospective study.

In a prospective study, patients with quiescent rheumatic heart disease (CRHD), streptococcal pharyngitis (SP) and healthy normal subjects produced comparable amounts of IL-1 and IL-2, but acute rheumatic fever (ARF) patients produced significantly elevated amounts of IL-1 and IL-2 at all intervals up to 48 weeks. In active rheumatic heart disease (ARHD), IL-1 activity returned to within normal range at 48 weeks, but IL-2 activity remained persistently elevated compared with CRHD, SP and healthy age- and sex-matched volunteers. CD4+ T lymphocytes were significantly increased in the peripheral blood of ARF and ARHD patients. The amount of IL-2 produced by ARF and ARHD patients correlated with the percentage of helper T lymphocytes (CD4+ cells) but not with the percentage of suppressor/cytotoxic T lymphocytes (CD8+ cells). Moreover, pre- and post-phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cell (PBMC) cultures from ARF and ARHD patients contained higher proportions of IL-2R+ (CD25+) cells than those from patients with SP, CRHD and normal individuals, which persisted up to 48 weeks. The percentage of CD25+ cells in both types of PBMC cultures directly correlated with the percentage of CD4+ cells and not with CD8+ cells in active rheumatic patients only. These findings indicate that the immune response in ARF and ARHD patients is skewed to produce activated helper T cells that release IL-2 which drives the accumulation of more T helper cells. The result is an undamped helper T cell response in the peripheral blood of these patients.

Effect of nifedipine administration on the functional capacity of neutrophils.

Administration of nifedipine to mice over a period of six months caused a significant (p < 0.05) decrease in neutrophilic functions viz superoxide generation, coupled to NADPH oxidase activity as well as NADPH production by HMP shunt. Properties like chemotaxis and phagocytosis showed a similar decrease. From this study, it is seen that nifedipine causes neutrophil functional abrogation which is therefore an apparent concern for the prolonged usage of the drug. However, relevance of the mouse model to clinical situation needs further investigation.

Epidemiology of rheumatic fever and rheumatic heart disease in a rural community in northern India.

The epidemiology of rheumatic fever and rheumatic heart disease in a rural community (total population 114,610) in northern India was studied by setting up a registry based on primary health care centres. Health workers and schoolteachers were trained to identify suspected patients in school and village surveys (121 villages). Medical specialists screened 5-15-year-olds (n = 31,200). The population was followed up for 3 years (from March 1988 to March 1991). All suspected and registered cases were investigated by serial echocardiography and Doppler ultrasonography at a tertiary care centre. A total of 102 cases were confirmed to have rheumatic fever/rheumatic heart disease (prevalence, 0.09%); 66 were aged 5-15 years (prevalence, 0.21%). A total of 48 patients (24 males, 24 females; mean age, 12.11 +/- 3.7 years) were diagnosed to have a possible first attack of rheumatic fever (incidence, 0.54 per 1000 per year). Arthritis was observed in 36 (75%) and carditis in 18 (37.5%) of cases. Prolapse of the anterior mitral leaflet into the left atrium occurred in 5 (22%) cases with carditis. Mitral regurgitation was observed in all 18 cases of carditis; over the period of observation it disappeared in three cases and progressed to mitral stenosis in a further three. A total of 22 patients (11 males, 11 females; mean age, 19.41 +/- 8.1 years) were registered as rheumatic fever recurrences, and 32 patients (18 females, 14 males; mean age, 22.1 +/- 10.1 years) had chronic rheumatic heart disease. Of those with recurrences, 9 (41%) had carditis and 11 (50%) had arthritis.(ABSTRACT TRUNCATED AT 250 WORDS)

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)

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.

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.

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.

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.

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.

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.

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)

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.

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.