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Biomedical subjects

A M Sharma

Publications and source records attributed to A M Sharma.

At least 145 records · Page 8Linked to original sources

Salt sensitivity in young normotensive subjects is associated with a hyperinsulinemic response to oral glucose.

Insulin resistance associated with a hyperinsulinemic response to oral glucose intake has been found in patients with essential hypertension and is believed to play a role in inducing hypertension by causing renal sodium and water retention. We therefore examined whether salt-sensitive, young normotensives, assumed to be predisposed to essential hypertension, exhibit impaired glucose tolerance in a similar way. The plasma insulin and glucose response to oral glucose intake (75 g) was assessed in 23 healthy, lean, male volunteers ingesting either 20 mmol or 260 mmol NaCl/day for 6 days each in a single-blind randomized crossover study. Salt sensitivity was defined as a significant drop in mean arterial blood pressure greater than 3 mmHg (means of 30 readings in the supine subject; P less than 0.05) under the low-salt diet. Following the glucose load, plasma levels of both glucose and insulin were significantly higher (P less than 0.01) in the salt-sensitive (n = 10) compared with the salt-resistant subjects (n = 13) during the high-salt diet but not during the low-salt diet. Whereas in the salt-sensitive group glucose tolerance improved with dietary salt restriction (P less than 0.01), it deteriorated in the salt-resistant group (P less than 0.05). Following the glucose load under the high-salt diet, there was a significant drop in blood pressure in the salt-sensitive (P less than 0.005) but not the salt-resistant subjects. The hyperglycemic and hyperinsulinemic response in salt-sensitive subjects suggests that insulin resistance is present in these subjects prior to the development of hypertension and that it can be ameliorated by salt restriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Somatostatin-induced hyperkalemia in a patient on maintenance hemodialysis.

A 65-year-old man, who had been undergoing maintenance hemodialysis for 20 years, suffering from severe postprandial hypotension was studied on 2 consecutive interdialytic days. The drop in blood pressure resulting from the oral administration of 75 g glucose was prevented by the concomitant infusion of somatostatin (350 micrograms/h), but this was accompanied by severe hyperkalemia (7.4 mmol/l). Suppression of insulin by somatostatin may have contributed to the hyperkalemia by impairing cellular potassium uptake. We conclude that although somatostatin prevents postprandial hypotension, hyperkalemia may limit its use in patients with end-stage renal failure.

Aged↗

Talc granulomatosis: two unusual presentations.

Two patients with history of intravenous drug use and pulmonary talc granulomatosis are presented. The first patient is a black female who was found to have increased activity of serum angiotensin converting enzyme, in addition to other clinical manifestations of sarcoidosis. The second patient is a Hispanic male smoker who presented with a solitary lung nodule and underwent transbronchial biopsies on two separate occasions with the diagnosis of talc granulomatosis. The lung nodule was found to be an adenocarcinoma on resection. Both patients had lung functions consistent with obstructive airways disease.

Adenocarcinoma↗

Abnormal acid-base regulation in salt-sensitive normotensive man.

Metabolic acidosis has recently been observed in rat models of salt-sensitive genetic hypertension. Studies in normotensive salt-sensitive men have likewise demonstrated slightly but significantly lower arterial pH and bicarbonate levels, relating salt-sensitivity to the presence of a relative acidosis in man. The administration of alkalinizing sodium salts such as sodium bicarbonate or citrate have been shown to have no effect on or to even lower blood pressure in patients with essential hypertension. Possible factors contributing to the perturbation in acid-base status include an enhanced Na+/H(+)-antiport activity, lower intracellular pH levels and altered renal electrolyte handling as found in rat models of hypertension and in patients with essential hypertension.

Acid-Base Imbalance↗

Sarcoidosis of the nervous system. A clinical approach.

Sarcoidosis is a multisystem disorder of unknown cause. The disease is characterized by the presence of noncaseating granulomas in the affected tissue system. Clinically recognizable nervous system involvement occurs in about 10% of patients with sarcoidosis, although the incidence of subclinical neurosarcoidosis is much higher. The disease appears in the differential diagnosis of many infectious and noninfectious neurological syndromes. We have reviewed all aspects of neurosarcoidosis from the point of view of practicing internists, including the clinical manifestations, cerebrospinal fluid and radiographic changes, differential diagnosis, and treatment.

Cranial Nerve Diseases↗

Dietary sodium restriction: adverse effect on plasma lipids.

In order to examine the effect of dietary sodium intake on plasma lipids, 15 healthy male volunteers were given a low-salt diet (20 mmol/day) for 3 weeks, adding either placebo, sodium chloride (200 mmol/day), or a non-chloride sodium salt (sodium citrate, 200 mmol Na/day) for one week each, in a single-blind randomized crossover study. Plasma levels of total cholesterol and LDL cholesterol were significantly higher at the end of the placebo period than with either sodium chloride (by 8.7 and 11.9%, respectively) (P less than 0.005) or sodium citrate (by 11.3% and 16.8%, respectively) (P less than 0.005). Thus this effect was dependent on sodium but not on chloride intake. Triglyceride and HDL-cholesterol levels were not affected by the dietary regimens. We conclude that short-term dietary sodium restriction may lead to a rise in plasma total and LDL cholesterol, thereby possibly increasing the risk of atherosclerotic vascular disease. Our findings render it possible that diuretic-induced lipid disturbances may also be caused by sodium depletion.

Adult↗

Repeated dialysis anaphylaxia.

A 76-year-old woman with multiple allergic reactions was treated 17 times by haemodialysis. Symptoms of anaphylactoid reactions of increasing severity led to final death due to cardiorespiratory arrest. Anaphylactoid reactions appeared 5-30 min after the start of dialysis and lasted for 15-20 min. They first occurred on the 7th dialysis and consisted of hypotension, diarrhoea, bronchospasm, bradycardia and respiratory arrest. Change of dialysis regime, dialyser (gamma-sterilised, autoclaved), heparin, and administration of antihistamines, steroid, and adrenaline did not prevent these reactions.

Aged↗

Salt sensitivity in humans is associated with abnormal acid-base regulation.

Metabolic acidosis has recently been observed in rat models of salt-sensitive genetic hypertension. To test the hypothesis that salt sensitivity in humans may be associated with abnormal acid-base homeostasis, we performed arterial blood gas analyses in young (20-31 years old) normotensive subjects (n = 40) who were placed on a low salt diet (20 mmol NaCl/day) for 2 weeks with either 200 mmol sodium chloride or placebo added to the low salt diet for 1 week each in a randomized, single-blind crossover order. Furthermore, a subset of the subjects (seven salt-sensitive and eight salt-resistant) received 200 mmol sodium/day as the citrate salt as a supplement to the low salt diet for a third week. During each regimen, blood pressure as well as arterial pH and bicarbonate levels were measured. Salt sensitivity was defined as a significant drop in mean arterial pressure greater than 3 mm Hg (mean of 30 readings taken during each diet, p less than 0.05) while the subject was on the low salt diet. According to this definition, 16 subjects were salt-sensitive and 24 salt-resistant. During the high sodium chloride regimen, arterial pH and bicarbonate levels were significantly lower in the salt-sensitive than in the salt-resistant group (p less than 0.0001). The increase in blood pressure caused by sodium chloride correlated inversely to the arterial pH (r = -0.57, p = 0.0002) and bicarbonate levels (r = -0.52, p = 0.0007) during the high salt diet. Sodium chloride increased mean arterial blood pressure in the salt-sensitive subjects; sodium citrate did not. Sodium citrate led to an increase in pH and bicarbonate levels in both groups. Our finding that a sodium chloride-induced rise in blood pressure is associated with lower arterial plasma pH and bicarbonate levels points to an abnormality in renal acid-base regulation in salt-sensitive subjects.

Acid-Base Equilibrium↗

Reliability of salt-sensitivity testing in normotensive subjects.

We examined the reliability of dietary salt-sensitivity testing by repeatedly studying the effects of a high (220 mmol/day) and low (20 mmol/day) salt diet in 15 normotensive subjects. Reliability of classification of salt-sensitivity as described by the kappa statistic was 0.87 implying an almost perfect strength of agreement between the two parts of the study. Whereas only 20% of the subjects with negative familial histories of hypertension were salt-sensitive, this was the case with 68% of the subjects with positive familial histories. Our results show that salt-sensitivity can be reliably tested in normotensive subjects and that it is related to a familial history of hypertension.

Adult↗

Quinine dosage in severe malaria with renal failure necessitating haemodialysis.

For therapy of severe malaria with renal failure, a 2/3 reduction in the usual intravenous dose of quinine is recommended (600 mg per 24 h instead of 600 mg per 8 h). Two patients with severe malaria and renal failure requiring dialysis have been treated. The half-life was not prolonged (15 h). Quinine proved to be nondialysable. It was shown that this dose of quinine tended to lead to a low level in blood (under 10 mg.l-1). A normal dose of quinine (2 x 15 mg/kg per day) is therefore recommended for malaria therapy, even in cases with renal failure requiring haemodialysis, in order to attain the desired plasma level (5 to 15 mg.l-1).

Chromatography, High Pressure Liquid↗

Sympathetic nervous activity and noradrenaline reactivity during angiotensin converting enzyme inhibition.

The effect of the angiotensin converting enzyme inhibitor ramipril on catecholamine disposition and noradrenaline reactivity was studied in normotensive volunteers. In the first study 5 mg of ramipril or placebo was given 3 times at 12-hour intervals in a randomized, double-blind, cross-over manner (n = 10). In the second study, ramipril 10 mg daily was given for 2 weeks (n = 6). Noradrenaline reactivity increased significantly (p less than 0.05) both in short- and long-term application, while blood pressure decreased (p less than 0.01). Sulfoconjugated plasma noradrenaline decreased significantly (p less than 0.05) possibly indicating a decrease in sympathetic tone. These findings suggest that a decrease in sympathetic tone could contribute to the blood pressure-lowering effect of ramipril, whereas the increase in noradrenaline reactivity is probably a consequence of the primary change in sympathetic activity.

Adult↗

Obesity and cardiovascular hemodynamic function.

Marked abnormalities in cardiovascular structure and hemodynamic function are present both in normotensive and hypertensive obese individuals. Cardiac abnormalities include excentric left ventricular hypertrophy and left atrial dilatation, a finding compatible with the presence of cardiac volume overload. In contrast, hypertension, often associated with abdominal obesity, is characterized by increased peripheral resistance and concentric hypertrophy. Weight reduction can result in marked improvement of ventricular dimensions and cardiac function in patients undergoing massive weight reduction following bariatric surgery. In this paper we review recent findings that have broadened our understanding of cardiovascular hemodynamic function in obesity.

Blood Pressure↗

Role of adipose tissue for cardiovascular-renal regulation in health and disease.

Obesity is associated with profound alterations of the cardiovascular system including an increase in systemic blood pressure. Several vasoactive factors, including non-esterified fatty acids, angiotensin II, prostaglandins, and nitric oxide are known to be produced by adipose tissue, and are therefore of particular interest regarding their potential role for the regulation of vascular tone and structure. In addition, central nervous system actions of the adipose tissue-derived hormone leptin may contribute to increased sympathetic nervous system activity that is typically found in obesity. Enhanced leptin-driven renal sympathetic out-flow, in combination with low atrial natriuretic peptide plasma levels possibly due to over-expression of the natriuretic peptide clearance receptor in adipocytes, may enhance sodium retention and volume expansion, both key features in the pathophysiology of obesity-associated hypertension. In this review, we discuss these and other possible contributions of adipose tissue to the regulation of cardiovascular-renal function and speculate on the role of adipose tissue for the development of obesity-associated hypertension.

Adipose Tissue↗

Comparison of the efficacy and safety of losartan (50-100 mg) with the T-type calcium channel blocker mibefradil (50-100 mg) in mild to moderate hypertension.

The objective of this study was to compare the antihypertensive efficacy and safety of losartan and mibefradil. 324 outpatients (57 +/- 9.2 years) with mild to moderate hypertension were randomly allocated in a double-blind fashion to receive 50 mg of losartan or mibefradil once daily p.o. for 6 weeks after 2 weeks of placebo run-in. Titration was then forced to 100 mg of losartan or mibefradil for an additional 6 weeks. Patients were assessed at baseline, 6 and 12 weeks. The primary efficacy variable was change in predose sitting diastolic (SDBP) and systolic (SSBP) blood pressure at 12 weeks. Secondary variables included change in mean 24-hour ambulatory blood pressure and comparison of safety and tolerability. Both treatments lowered SSBP and SDBP at 6 and 12 weeks (week 6: mibefradil -14/-9 mm Hg; losartan -12/-7 mm Hg) (P <0.001). The primary objective, a difference between treatments in reduction of SSBP and SDBP at week 12 could be demonstrated (mibefradil -22/-16 mm Hg; losartan -16/-10 mm Hg) (P=0.003 and P=0.001, respectively). Twenty-four-hour SBP and 24-hour DBP were reduced (P<0.001) within each treatment group at weeks 6 and 12. The secondary objective, a difference between treatments in reduction of 24-hour blood pressure at week 12 could be demonstrated (P<0.001). Twenty-four-hour heart rate was lowered in the mibefradil group at weeks 6 and 12 (P < 0.001). Responder rates at 6 and 12 weeks were 56.2% and 78.5% for mibefradil versus 56.1% and 55.3% for losartan (P = 0.001). Both treatments were equally well tolerated. This study demonstrates that 50 mg losartan is comparably effective to 50 mg mibefradil in the treatment of mild to moderate hypertension with 100 mg mibefradil being more potent than losartan.

Adolescent↗

Asthma mortality in a metropolitan county hospital, a 38-year study.

A 38-year (1949-1986) retrospective chart review of 535 decedent asthmatic patients was undertaken to determine trends in asthma-related deaths. Records of 187 decedents with clinical and autopsy evidence were analyzed. An overall decrease in asthma-related deaths over the four interval periods of the study was noted. Thirty-five percent of the patients died within 24 hours, and 85% died within 7 days of admission. Seventy-five percent of decedents were greater than 40 years of age. Fifty-two percent of the patients were white, 34% black, and 13% Hispanic. Mortality was higher in younger (less than 40 years) blacks and in older (greater than 40 years) whites. The number of deaths was inversely proportional to the number of patients managed in the pulmonary/ICU setting. Longer duration (greater than 10 years) of asthma was associated with a higher (60%) mortality. Mucus plugging occurred in 74% of patients. Previous hospitalization (93%), previous intubations, and inadequate assessment (peak expiratory flow rates, pulsus paradoxus) also were associated with higher mortality.

Age Factors↗