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.

Myocardial lesions induced by prolonged alcohol feeding in rhesus monkeys.

To elucidate the effects of chronic alcohol ingestion in monkeys a synthetic, adequately balanced, fluid diet providing 40% of total calories from ethanol was gavaged through a stomach tube daily over a period of three months. Clinical, biochemical, radioisotope, and histopathological studies were performed at the beginning and end of the experiment. It was observed that chronic alcohol feeding at this dose level caused maked accumulation of triglycerides, cholesterol, and phospholipids in the serum and the liver. In the heart triglycerides and cholesterol ester were increased. Incorporation studies showed increased synthesis of triglycerides in the heart muscle and liver. Histologically the heart showed fatty change of the myocardium and evidence of focal myocytolysis, atrophy of muscle bundles, and early fibrosis. The liver showed generalized fatty change but no cirrhosis.

Pseudohypertrophic myopathy in cysticerosis.

A patient with diffuse involvement of the central nervous system and pseudohypertrophic muscular changes induced by cysticerci is described. Electromyographic and pathologic changes are reported for the first time. Electromyographic examination demonstrated numerous short-duration, low-amplitude motor unit potentials in proximal muscles. Biopsy showed swelling of muscle fibers, fiber atrophy with fibrosis, and cellular infiltration separate from inflammatory exudate surrounding numerous cysts.

Serum lipid profiles in patients of myocardial infarction in the Chandigarh area (Northern India).

To study the incidence of hyperlipoproteinaemia in patients with myocardial infarction (MI) in the Chandigarh area, estimations of various lipids have been carried out in 83 patients. A serial study has been carried out in 31 patients. Serum lipoproteins and uric acid were also estimated. Results show an incidence of only 18% hypercholesterolaemia in patients with MI and 15% in normal subjects. Age-wise distribution of hypercholesterolaemia was slightly higher in 41-60 years old patients when compared with other age groups. No other abnormality in lipid profile was observed. Hyperuricaemia was not observed. These results, therefore, differ markedly from those of similar studies published from the western world.

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.

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)

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.

Humoral immunity in experimental immune carditis.

An experimental model of carditis has been produced in the rhesus monkey by giving 12 weekly injections of a streptococcal membrane antigen. There was histological evidence of focal myocarditis, subendocardial infiltration with lymphomononuclear cells and in one animal myocardial granuloma formation. No valvular lesions were seen. Humoral immune responses monitored throughout the experiment showed that anti-heart antibodies appeared in circulation after the 2nd injection, attained maximal titres by the 6th injection, and thereafter the titres declined. The anti-membrane antibodies appeared slightly later and these titres kept rising till sacrifice. By the 6th injection there was evidence of complement consumption and appearance of circulating immune complexes. It is concluded that these immunological responses might have a role to play in the pathogenesis of carditis.

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)

Enalapril as initial and sole treatment in severe chronic heart failure with sodium retention.

Five patients, who had never received any drug treatment but who had severe chronic congestive heart failure with salt and water retention, were studied before and after a single dose of enalapril (10 mg orally). Three patients continued on enalapril as monotherapy (10 mg b.d. orally) for one month. Central haemodynamics, body fluid volumes, renal function and plasma hormones were measured at rest. The initial mean right atrial pressure was 13 +/- 4 mm Hg, pulmonary wedge pressure 29 +/- 4 mm Hg and cardiac index 1.8 +/- 0.21/min/m2. Enalapril, given acutely, caused only small changes. Two patients were withdrawn after the single dose of enalapril and treated with diuretics for clinical reasons. The remaining three patients each lost more than 4 kg in weight after one month of treatment with enalapril alone. Total body exchangeable sodium and total body water were reduced but central haemodynamics were unchanged. Although enalapril was of some benefit when given alone to patients with severe congestive heart failure, all five patients were finally treated with diuretics for clinical reasons. Enalapril is not recommended as the initial and only therapy for patients with severe congestive heart failure.

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.

Evaluation of a simpler technique for in-vivo labelling of red blood cells with 99mTc.

The efficiency of labelling red blood cells with intravenously administered 99mTcO4, by prior oral administration of stannous chloride dihydrate, has been evaluated. Optimum labelling occurred 1 hr after the oral dose of 200 mg of SnCl2.2 H2O and 20 min after the intravenous injection of 99mTcO4. The mechanism of labelling has been shown to be diffusion of 99Tc through the cell membrane followed by binding to haemoglobin in the presence of reducing agent. The in-vivo labelling technique has been found to be useful for the diagnosis of an abdominal mass and for static perfusion studies.

Thromboangitis obliterans: a clinical study with special emphasis on venous involvement.

Sixty-one cases of thromboangitis obliterans (TAO) were studied during 1969-70. Nearly all were males, smokers, of poor socio-economic status. Average age of presentation was 34.2 years. A majority (64%) presented with claudication pain. About one fifth gave history of migratory thrombophlebitis and venography and histological investigations suggested that sixty per cent had venous involvement. Nearly half the patients had involvement of upper limb vessels. Clinical and arteriographic studies showed femoral-popliteal junction to be the commonest site of block. No evidence of coronary artery disease, cerebral vascular disease, abnormal glucose and lipid metabolism was seen in these patients. Arteriographic findings were unlike atherosclerosis obliterans (ASO). From this study we conclude that thromboangitis obliterans (TAO) is a separate and distinct clinical and pathologic entity and the incidence of venous involvement is very high if venographic investigations are combined with clinical examination.

A rheumatic fever and rheumatic heart disease control programme in a rural community of north India.

BACKGROUND: This study was conducted in a rural community of north India to evaluate a rheumatic fever and rheumatic heart disease control programme which used the existing health and educational infrastructure. METHODS: A health education campaign was launched in a rural community block (population 140 000) with a similar non-contiguous block (population 180 000) serving as a control. In the intervention block, 74 primary health workers, 773 teachers and 12 500 students were trained to suspect the disease. Twelve medical officers in four health centres registered patients, who were put on secondary prophylaxis with penicillin or sulphonamide, and monitored their compliance. All the cases were examined by a cardiologist to confirm the diagnosis; if the diagnosis was not confirmed secondary prophylaxis was stopped. RESULTS: In the two years preceding intervention, 13 cases (case detection rate 3.6/100 000 population/year) were detected from the health centre records in the control and 22 (7.8/100 000/year) from the intervention block. During the two years of study 16 new cases (4.4/100 000/year) were registered in the control block whereas 254 suspected cases of rheumatic fever and rheumatic heart disease were referred to medical officers in the intervention block. Of these, 77 new cases (27.5/100 000/year) were registered, of which 61 (79%) were subsequently confirmed to have the disease- 48 had chronic rheumatic disease and 13 their first attack of acute rheumatic fever. Secondary prophylaxis in the form of penicillin or sulphonamide was instituted in these patients with a compliance of 85% to 95%. CONCLUSIONS: In developing countries, it is possible to successfully apply a secondary prevention programme for the early detection of rheumatic fever and rheumatic heart disease using existing primary health care auxiliaries, school teachers and pupils at an affordable additional cost.

Catecholamine-induced experimental cardiomyopathy--a histopathological, histochemical and ultrastructural study.

An experimental model of myocardiopathy was induced in rhesus monkeys following noradrenaline (NA) infusion (20 ug/kg body wt/minute), for a period of 2 hours daily for three consecutive days. The animals were sacrificed after two hours (acute phase), forty-eight hours (sub-acute phase) and twenty-one days (chronic phase). Focal depletion of succinic dehydrogenase, increase in adenosine triphosphatase, acid phosphatase and appearance of large fat droplets in myocardial muscle was noted in the acute phase. Histopathological examination revealed focal edema, opacity and fuchsinorrhagia of the muscle fibres distributed in both the ventricles. Myofibrillar degeneration, myocytolysis and vacuolization with aggregation of lymphomononuclear cells were the significant features in the acute phase. During sub-acute and chronic phases, these features became less prominent and reparative changes with proliferation of fibroblasts became more marked. By the twenty-first day, irregular, focal scars replaced the necrosed myocardium. Ultrastructurally, heart muscle showed myofibrillar disorganisation, distortion of Z and A bands, dilatation of sarcoplasmic reticulum and swelling and rupture of mitochondria. Altered membrane permeability was evidenced by the presence of reaction products of horseradish peroxidase within the cardiac cells. In the reparative phase, however, myocytolytic changes regressed and collagen deposition was the prominent feature. This experimental study has several histological features simulating human cases of myocardial infarction without coronary occlusion.

Aluminium phosphide poisoning: haemodynamic observations.

Haemodynamic measurements were made on 25 patients with aluminium phosphide poisoning. There was severe hypotension (mean arterial pressure 62.7 +/- 19.3 mmHg) and reduction in cardiac output (2.13 +/- 0.9 lit/min/m2). However, the systemic vascular resistance was only moderately elevated (2050 +/- 732 dynes/m2). The right atrial pressure was increased but the pulmonary artery and pulmonary capillary wedge pressures were normal, even in patients with pulmonary oedema. Thirteen patients (52%) who died had a lower cardiac output (p less than 0.05). Saline infusion significantly improved haemodynamics in some patients. Its judicious use early in the course of treatment may be beneficial.

Evaluation of pulmonary hypertension in chronic rheumatic mitral regurgitation.

The incidence of pulmonary arterial hypertension (PAH) in 39 patients with angiographically proven chronic rheumatic mitral regurgitation (MR) is reported. The overall incidence of PAH were found to be 76.9%. There were 51.3% patients with mild, 15.4% with moderate and 10.2% with severe PAH. Pulmonary arterial hypertension was present in 93% of patients below 20 years of age. Clinical and radiological assessment of PAH did not show any correlation with the haemodynamic data. Electrocardiographic right ventricular hypertrophy was seen in 4, and biventricular hypertrophy in 5 patients. All of them had moderate to severe PAH. Echocardiographic left atrial (LA) size showed an inverse correlation with mean pulmonary artery pressure (PAP) (p less than 0.001), r = 0.63). Presence of mid-systolic notch in pulmonary valve echoes indicated mean PAP more than 37mmHg (mean 54.1 +/- 19.1). Fifty-six percent patients with mid-systolic notch had moderate to severe PAH. Sixteen (94%) out of 17 patients with raised left ventricular end diastolic pressure had elevated mean PAP, and 30% of them had moderate to severe PAH. This data shows that pulmonary hypertension is relatively common in our patients with chronic rheumatic MR, and that the severity of PAH correlates well.

Brain abscess in cyanotic congenital heart disease.

Twenty-eight patients of cyanotic congenital heart disease (CHD) complicated with brain abscess were reviewed. There were 22 males and 6 females with a mean age of 9.1 +/- 5.5 years. Tetralogy of Fallot was the commonest cyanotic CHD observed. Transposition of great arteries (PS), tricuspid atresia with VSD, PS and double outlet right ventricle with VSD comprised 25% of the cardiac lesions. Febrile illness was the commonest mode of presentation (42.86%). Frontal lobe was the commonest site of abscess localization (37.5%) followed by parietal lobe (32.5%). Multiple abscess were seen in 32.14% and in 35.7% the pus was sterile on culture. Twelve patients died (mortality -42.8%), and autopsy reports were available in 6. Infective endocarditis was suspected in 7 on clinical grounds, while at autopsy, out of 6 only 2 had evidence of right-sided endocarditis. There was no correlation of mortality with age, sex, type of micro-organism, site of abscess localization and the nature of heart disease. Multiple abscesses, features of raised intracranial tension and associated meningitis/ventriculitis predicted a grim outcome.

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.

Pregnancy with heart disease. Experience at Postgraduate Institute of Medical Education and Research, Chandigarh.

Pregnant patients with heart disease seen between 1980 and 1985 were studied. The incidence of heart disease in pregnancy was 1.3%. Rheumatic heart disease was the commonest lesion (78%), followed by congenital heart disease (18.7%). In the rheumatic heart disease group, mitral stenosis was the commonest lesion (71.54%), and patients who had been or were operated on for their heart disease had less severe dyspnoea and fewer complications. The mode of delivery and the foetal and maternal mortality did not differ significantly in operated and non operated patients.