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Biomedical subjects

J Mehta

Publications and source records attributed to J Mehta.

At least 37 records · Page 2Linked to original sources

Effect of L-arginine and an arginine-containing pentapeptide on canine femoral arterial blood flow.

The amino acid L-arginine is a precursor of endothelium derived relaxing factor (EDRF). The pentapeptide 6A (Ala-Arg-Pro-Ala-Lys) released by plasmin degradation of fibrinogen also contains arginine and relaxes vascular smooth muscle by releasing EDRF (nitric oxide). To determine and compare the effects of L-arginine, peptide 6A and a combination of L-arginine and peptide 6A on femoral artery blood flow and vascular resistance, anesthetized mongrel dog were administered saline, L-arginine, D-arginine, peptide 6A and L-arginine + peptide 6A in a random order. L-arginine and peptide 6A both induced an immediate dose-dependent short-lasting increase in femoral blood flow and a decrease in vascular resistance. Peptide 6A exerted a much greater (P less than 0.01) vasodilatory effect than did L-arginine at the same molar concentration suggesting that properties besides the arginine content are important in the effect of the pentapeptide. D-arginine had much less effect than L-arginine, indicating that the effect of L-arginine may be related to its utilization for synthesis of EDRF. When the peptide 6A was given soon after L-arginine, its effect on blood flow was not greater than that of L-arginine alone suggesting that L-arginine in a large amount makes guanylate cyclase less available for the more active peptide.

Amino Acid Sequence

"Ring around the artery" as a presenting feature in undiagnosed asthma with pneumomediastinum.

Acute bronchial asthma may be complicated by pneumomediastinum, often accompanied by the "ring around the artery" sign, described in association with asthma, trauma (gunshot wound), subclavian catheterization, and cocaine use, or with no identifiable risk factors. The diagnosis of pneumomediastinum should always be considered in an asthmatic patient with chest pain, cough, and dyspnea. Lateral chest film reveals a radiolucency outlining the right pulmonary artery. Such patients recover spontaneously with conservative therapy.

Acute Disease

Fiberoptic bronchoscopy in the diagnosis of pulmonary tuberculosis.

We reviewed the records of 80 patients with culture-positive pulmonary tuberculosis. Forty (50%) had their diagnoses established by sputum smears and cultures alone, 20 (25%) by brush/wash specimens from fiberoptic bronchoscopy alone, 18 (22.5%) from both sources, and two (2.5%) by gastric smears. The average age of the patients was 71.3 years, and only 20% had symptoms typical of pulmonary tuberculosis. Our data reveal that findings in smears from fiberoptic bronchoscopy were of comparable sensitivity (80%) to those of sputum (72.5%); in 25/80 (31.25%), diagnosis was made exclusively by fiberoptic bronchoscopy. Such a high sensitivity of fiberoptic bronchoscopy in the diagnosis of pulmonary tuberculosis indicates a threefold rise (P = .018) in the number of diagnoses made in this manner compared to our figures from 1983 (10% of diagnoses made by fiberoptic bronchoscopy). Forty-three of the 80 patients (53.8%) had either a negative sputum smear or no sputum available. Thirty of the 43 patients (69.8%) had diagnostic bronchoscopy, which provided an immediate diagnosis (smear positivity) in 18 patients (60%). Transbronchial biopsy was most useful in excluding associated malignancy. Fiberoptic bronchoscopy is playing an increasingly significant role in the diagnosis of pulmonary tuberculosis. Further studies are essential to evaluate cost effectiveness, specificity of fiberoptic bronchoscopy, and the influence of the procedure on morbidity and mortality in pulmonary tuberculosis.

Age Factors

Neutrophil function in ischemic heart disease.

Neutrophils contribute to the healing of and scar formation in myocardium after ischemic injury. Many recent studies indicate that neutrophils may be involved in the genesis and propagation of myocardial ischemia. To characterize neutrophil function in ischemic heart disease, neutrophil chemotaxis, leukotriene B4 (LTB4) generation, and elastase release in plasma were measured in 20 patients with stable angina, 17 patients with unstable angina or acute myocardial infarction (AMI), and 20 age-matched control subjects. Neutrophils from patients with stable angina exhibited markedly increased chemotactic activity and LTB4 generation as compared with the age-matched control subjects (p less than 0.01). Neutrophils of nine of 17 patients with unstable angina or AMI clumped spontaneously ex vivo and exhibited marked pseudopod formation and granule extrusion on electron microscopy. Subsequent chemotactic activity and LTB4 generation by neutrophils from these patients was less than in patients with stable angina, suggesting previous in vivo activation. Plasma levels of peptide B beta, a product of fibrin degradation by human neutrophil elastase, were approximately 15-fold higher (p less than 0.001) in patients with unstable angina or AMI (588 +/- 171 pmol/l, mean +/- SEM) compared with those in patients with stable angina (37 +/- 25 pmol/l) or control subjects (40 +/- 22 pmol/l), confirming intense in vivo neutrophil activation. Our study shows enhanced neutrophil function in patients with ischemic heart disease. The increased neutrophil chemotactic activity and LTB4 generation may be markers of stable angina pectoris. Intense neutrophil activation in unstable angina or AMI, as manifested by morphologic changes in neutrophils and elastase release, may relate to ongoing in vivo cellular activation.

Chemotaxis, Leukocyte

Reduced myocardial neutrophil accumulation and infarct size following thromboxane synthetase inhibitor or receptor antagonist.

Since thromboxane A2 (TXA2) release may relate to the extension of myocardial injury following coronary ligation, the authors examined the effects of pretreatment with a selective TXA2 synthetase inhibitor U-63,557A, or a TXA2 receptor antagonist SQ-29,548, on myocardial infarct size forty-eight hours following left coronary ligation in rats. Myocardial infarct size (as percent of left ventricle, LV) was decreased from 44 +/- 3% in saline-treated control animals to 34 +/- 4% (P less than 0.05) in U-63,557A-treated animals and to 32 +/- 4% (P less than 0.05) in SQ-29,548 treated animals (U-63,557A-treated vs SQ-29,548-treated, P = NS). LV creatine kinase (CK) was 5.08 +/- 0.42 IU/mg protein in noninfarcted untreated rats and 1.79 +/- 0.21 IU/mg protein in saline-treated infarcted rats. LV CK was 2.86 +/- 0.40 IU/mg protein in U-63,557A-treated rats and 3.11 +/- 0.51 IU/mg protein in SQ-29,548-treated infarcted rats (both P less than 0.05 compared with saline-treated rats). The beneficial effects of U-63,557A and of SQ-29,548 were not accompanied by reduction in indices of myocardial oxygen demand (heart rate and arterial pressure). However, neutrophil accumulation in the infarcted myocardium was markedly decreased by U-63,557A and SQ-29,548 pretreatment. Myocardial myeloperoxidase activity, a specific marker of neutrophil infiltration, was also decreased (P less than 0.02) in U-63,557A- and SQ-29,548-treated animals (0.09 +/- 0.03 and 0.07 +/- 0.02 units/100 mg, respectively) compared with saline-treated infarcted rats (0.19 +/- 0.04 units/100 mg). In vitro incubation of U-63,557A and SQ-29,548 caused a significant and similar reduction in f-MLP-induced neutrophil chemotaxis, and U-63,557A increased prostacyclin formation in whole blood. These data suggest that reduction in the extent of myocardial injury by TXA2 synthetase or receptor inhibitors may, in part, relate to a decrease in neutrophil accumulation in the infarcted tissue. In spite of differences in mechanisms of action of U-63,557A and SQ-29,548, both agents exert a similar protective effect on the extent of myocardial injury following coronary ligation. Reduction in neutrophil accumulation in the infarcted zone, as well as in f-MLP-directed chemotaxis in vitro, suggests that TXA2 inhibition may modulate neutrophil migration.

Animals

Lisinopril versus lisinopril plus hydrochlorothiazide in essential hypertension.

The efficacy of a new angiotensin converting enzyme inhibitor, lisinopril, used alone (group A) was compared with lisinopril plus hydrochlorothiazide (group B) in 26 patients with essential hypertension. Therapy with both regimens was equally effective in lowering blood pressure compared to placebo. Mean antihypertensive dose of lisinopril was lower when given in combination with hydrochlorothiazide than when given alone (48 +/- 6 vs 68 +/- 12 mg daily). Plasma renin activity increased in both groups of patients, but more in group B (p less than 0.05). Plasma aldosterone concentrations and serum uric acid levels were also higher in the group receiving lisinopril plus hydrochlorothiazide (p less than 0.05). Serum potassium concentrations were unaffected in either group. The incidence of side effects was similar in groups A and B (44% and 38%, respectively). This study suggests that lisinopril alone or in combination with hydrochlorothiazide effectively lowers blood pressure in patients with essential hypertension without any major side effects.

Angiotensin-Converting Enzyme Inhibitors

Enhancement of human neutrophil function by platelets: effects of indomethacin.

To characterize the influence of presence of platelets on human neutrophil function, neutrophil oxidative burst, chemotaxis, leukotriene B4 and prostacyclin generation were examined in the presence of physiologic concentration of platelets (40: 1). Presence of platelets significantly (P less than or equal to 0.05) increased all these neutrophil functions. To determine if cyclooxygenase products are involved in platelet-neutrophil interaction, neutrophils (+/- platelets) were incubated with indomethacin. Although high concentrations of indomethacin (10 microM) inhibited neutrophil (no platelets) chemotaxis and leukotriene B4 generation, these inhibitory effects of indomethacin were attenuated in the presence of platelets. Thus presence of platelets enhances neutrophil activity and overcomes the inhibitory effects of indomethacin on neutrophils.

Blood Platelets

The primary wave of epinephrine-induced platelet aggregation represents alpha 2-adrenoceptor status.

We examined relationships between epinephrine-induced slope of primary wave of aggregation and the alpha 2-adrenoceptor status on platelets. A concentration (10(-9) to 10(-6]-dependent increase in slope of primary wave with EC50 of epinephrine at 4.5 +/- 0.4 x 10(-7) was observed. In studies on epinephrine binding to alpha 2-adrenoceptors in competition with 3H-yohimbine to platelets, (IC50) of epinephrine was 4.8 +/- 3.4 x 10(-7) M. There was a significant (P less than or equal to 0.02) correlation between EC50 of epinephrine to evoke biological response and IC50 of epinephrine to bind to alpha 2-adrenoceptors (r-0.75). There was no relationship between number of receptor sites or dissociation constant of 3H-yohimbine binding and primary wave of platelet aggregation. These data show that the slope of primary wave in response to epinephrine reflects alpha 2-adrenoceptor binding of the agonist.

Adolescent

Reduction in plasminogen activator inhibitor-1 (PAI-1) with omega-3 polyunsaturated fatty acid (PUFA) intake.

Activity of plasminogen activator inhibitor-1 (PAI-1) in human blood correlates with thrombotic tendency and with serum triglyceride concentrations. Since intake of fish-derived omega-3 polyunsaturated fatty acids (PUFA) decreases serum triglycerides, we examined the effects of omega-3 PUFA maximum eicosapentaenoic acid (Max EPA) intake on PAI-1 levels in eight patients with coronary artery disease and in four normal subjects. After 4 weeks of Max-EPA intake by coronary artery disease patients, serum triglyceride concentrations and PAI-1 levels decreased 43 +/- 8% and 21 +/- 5%, respectively (both p less than or equal to 0.01) without any change in tissue plasminogen activator (TPA) levels. No changes were noted at 1 week of Max EPA intake in normal subjects, but at 3 weeks serum triglyceride concentrations and PAI-1 levels decreased 32 +/- 13% and 22 +/- 4%, respectively (p less than or equal to 0.01) without any change in tissue plasminogen activator (TPA) levels. No changes were noted at 1 week of Max EPA intake in normal subjects, but at 3 weeks serum triglyceride concentrations and PAI-1 levels decreased 32 +/- 13% and 22 +/- 4%, respectively (p less than or equal to 0.02) without change in TPA. The magnitude of reduction in triglycerides was dependent on the initial serum concentration (r = 0.68, p less than or equal to 0.01). In addition, decrease in PAI-1 levels correlated with reduction in serum triglycerides (r = 0.79, p less than or equal to 0.01). This study shows that omega-3 PUFA intake reduces PAI-1 levels without change in TPA antigen. These observations may relate to decrease in thrombotic activity upon consumption of large amounts of fish or fish-derived products.

Aged

Reproducibility of histology in leprosy lesions.

The variability of three commonly used histological parameters in leprosy histology was examined within and between lesions on individual patients by taking two biopsies, either from opposing edges of the same lesion or from the edge of two separate lesions. There was little variation in granuloma fraction (GF), bacterial index (BI), or histological classification on the Ridley-Jopling scale between biopsies from opposing edges of the same lesion, but there was considerable variation in the GF between biopsies from the edge of different lesions. A lesser degree of variation was seen in the BI between different lesions, and there was little difference in histological classification between established lesions. Thus, it appears that local factors influence the size of the leprosy granuloma, but its histological composition and bacterial load are determined systemically.

Adult

Ethanol stimulates prostacyclin biosynthesis by human neutrophils and potentiates anti-platelet aggregatory effects of prostacyclin.

Previous reports on the direct effects of ethanol on human platelet aggregation function have been inconsistent. Ethanol ingestion produces vasodilation and raises intracellular cyclic AMP concentrations, effects similar to those of prostacyclin. We, therefore, hypothesized that ethanol may influence biosynthesis and/or bioactivity of prostacyclin. In our experiments, ethanol in concentrations up to 400 mg% had no consistent inhibitory effect on platelet aggregation in response to epinephrine, ADP, or combination of subthreshold concentrations of epinephrine plus ADP. However, ethanol in concentrations as low as 10 mg% potentiated the platelet aggregation inhibitory effects of prostacyclin. In addition, ethanol (20 mg%) decreased formation of thromboxane A2 in whole blood by 41% and stimulated formation of prostacyclin by 160% (both P less than 0.01). Additional studies using isolated human cells demonstrated synthesis of prostacyclin by neutrophils in the presence of platelets, and this neutrophil prostacyclin formation was enhanced in the presence of ethanol. These effects of alcohol in concentrations achieved after moderate intake may relate to the hemodynamic, biochemical, and cardioprotective effects of ethanol.

Drug Synergism

Similar efficacy of nitrendipine in young and elderly hypertensive patients.

Calcium channel blockers have been postulated to be more effective as monotherapeutic antihypertensive agents in the elderly than in younger patients. To determine if a new dihydropyridine derivative, nitrendipine, is more effective in the elderly (older than 60 years) than in younger hypertensive subjects (younger than 60 years), nitrendipine was administered in a multicentered study to 21 elderly and 33 younger subjects with essential hypertension. After gradual discontinuation of previous antihypertensive therapy and 2 weeks of placebo, the daily dose of nitrendipine (10 to 40 mg) was titrated over 3 weeks to achieve a 10 mm Hg decrease in supine diastolic blood pressure (BP) for patients entering with 90 to 99 mm Hg. For patients entering with at least 100 mm Hg, the dose was titrated to diastolic BP no greater than 90 mm Hg. Titrated dose of nitrendipine was maintained for 4 additional weeks. Propranolol was added for "symptomatic" tachycardia. Nitrendipine reduced BP in 90% of patients completing all phases of the study (n = 49). The proportion of responders was 47% among the elderly and 44% among young subjects. Change in heart rate was similar in both groups (-0.1 +/- 9.9 and +2.9 +/- 8.8 beats/min, mean +/- standard deviation). Two elderly and 1 younger subject required addition of propranolol (difference not significant). There was no correlation between the age of patients and changes in supine systolic and diastolic BP or heart rate (r = 0.21, -0.15 and -0.21, respectively). Adverse effects occurred with equal frequency in older and younger subjects (19 of 21 vs 23 of 33 patients, difference not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult