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Biomedical subjects

M L Sharma

Publications and source records attributed to M L Sharma.

At least 19 recordsLinked to original sources
PubMed1992

Persistent paralysis in critically ill patients after long-term administration of vecuronium.

BACKGROUND: The muscle relaxant vecuronium is sometimes administered to facilitate mechanical ventilation. Neuromuscular paralysis lasting up to seven days may occur after the termination of long-term administration (i.e., more than two days) of vecuronium in critically ill patients. We investigated the role of clinical factors and plasma concentrations of vecuronium and its metabolite in causing this prolonged neuromuscular blockade. METHODS: We studied 16 critically ill adult patients (8 women and 8 men) who had received vecuronium to facilitate mechanical ventilation for at least two consecutive days. Clinical factors and plasma concentrations of vecuronium and 3-desacetylvecuronium, the active metabolite of vecuronium, were compared in patients with and without prolonged neuromuscular blockade. In addition, we performed detailed pharmacokinetic studies in the patients without prolonged neuromuscular blockade. RESULTS: Seven of the 16 patients had prolonged neuromuscular blockade, lasting from six hours to more than seven days, after the termination of vecuronium therapy. These seven patients, six of whom were women, had higher plasma magnesium concentrations and lower arterial blood pH values than the nine patients without prolonged neuromuscular blockade. They also had higher plasma concentrations of 3-desacetylvecuronium and a higher frequency of renal failure (seven of seven patients vs. four of nine patients, P less than 0.03). In the patients without prolonged neuromuscular blockade, the mean (+/- SD) plasma clearance, elimination half-life, and volume of distribution of vecuronium were 2.5 +/- 1.0 ml per kilogram of body weight per minute, 299 +/- 154 minutes, and 1.1 +/- 0.6 liters per kilogram, respectively. CONCLUSIONS: Prolonged neuromuscular blockade after the termination of long-term treatment with vecuronium is associated with metabolic acidosis, elevated plasma magnesium concentrations, female sex, and probably more important, the presence of renal failure and high plasma concentrations of 3-desacetylvecuronium.

Critical Illness↗
PubMed1992

Common aetiological agent for epidemic and sporadic non-A, non-B hepatitis.

Enterovirus-like particles have been reported in the acute phase of both epidemic and sporadic non-A, non-B (NANB) hepatitis. To examine whether these particles were the causative agent in the two types of disease, 29 patients with acute viral hepatitis in a north Indian epidemic outbreak and 9 with sporadic acute disease were investigated. 25 (86%) of 29 patients with epidemic hepatitis and 5 (56%) of 9 with sporadic disease were diagnosed as having enterically-transmitted-NANB hepatitis by exclusion. Virus-like particles (VLP) of 30-34 nm were detected in stool of 1 patient with epidemic and 1 with sporadic hepatitis. The VLPs crossreacted serologically and a specific IgM response was seen in acute epidemic and sporadic serum samples. After inoculation with infected stool rhesus monkeys had a mild rise in liver enzymes, and bile samples contained VLPs. These results suggest that the aetiological agent in epidemic and sporadic disease is the same.

Animals↗
PubMed1992

Immunopharmacological properties of azepino [2, 1-b] quinazolin-12(6H)-one-7, 8, 9, 10-tetrahydro (RLX).

The effect of azepino [2,1-b]quinazolin-12(6H)-one-7, 8, 9, 10-tetrahydro (RLX) was studied on cell-mediated and humoral components of the immune system. In single (50, 100 and 200 mg/kg) and multiple (6.25, 12.50, 25 and 50 m/kg) oral dose schedules RLX significantly reduced the early (4 h) and delayed (24 and 48 h) hypersensitivity reactions to SRBC in mice. Daily oral administration of RLX (25, 50 and 100 mg/kg) produced a dose-related reduction in developing adjuvant arthritis in rats. In carrageenan-induced pleurisy in rats RLX (25, 50 and 100 mg/kg p.o.) caused a marked reduction in the volume of pleural exudate (25.26-59.64%) and infiltration of leucocytes (28.75-50.29%) into the pleural cavity. RLX produced marked inhibition of humoral antibody synthesis both in mice and rats and that of complement fixing antibody in mice. It was not cytotoxic and showed no appreciable effect on the responsiveness of splenocytes to mitogens. The observed effect of RLX on cell-mediated and humoral immune responses does not appear to be the result of general toxicity.

Animals↗
PubMed1992

Pharmacokinetics of rocuronium bromide (ORG 9426) in patients with normal renal function or patients undergoing cadaver renal transplantation.

To determine the effect of end-stage renal disease on the pharmacokinetics of reocuronium bromide (ORG 9426), a new nondepolarizing monoquaternary steroidal neuromuscular blocking drug, the authors administered 600 micrograms/kg rocuronium (2 x ED95) intravenously to ten patients undergoing cadaver renal transplantation and ten healthy patients undergoing elective minor surgery (controls). All patients were anesthetized with nitrous oxide (50-70% in oxygen) and isoflurane (end-tidal concentrations of 1.2 +/- 0.5% and 0.8 +/- 0.2%, mean +/- SD, for control and transplant groups, respectively). Plasma concentrations of rocuronium were determined by capillary gas chromatography. A population-based pharmacokinetic analysis (NONMEM) was used to determine typical values, standard errors, and interindividual variability for the pharmacokinetic parameters and to determine whether these values differed between control and renal transplant patients. Total plasma clearance (2.89 +/- 0.25 ml.kg-1.min-1, mean +/- SE) and volume of the central compartment (76.9 +/- 10.6 ml/kg) did not differ between control and renal transplant patients, whereas volume of distribution at steady state was greater in renal transplant patients (264 +/- 19 ml/kg) than in control patients (207 +/- 14 ml/kg). This resulted in a longer elimination half life in renal transplant patients (97.2 +/- 17.3 min) compared to controls (70.9 +/- 4.7 min). The authors conclude that renal failure and renal transplantation alter the distribution but not the clearance of rocuronium.

Adult↗
PubMed1992

Failure to reduce experimental myocardial infarct size with ibuprofen pre-treatment in rats.

The prophylactic role of ibuprofen in experimental myocardial infarction has not been reported. Twenty-four rats pre-treated with ibuprofen (30 mg/kg), po, for 21 days were subjected to myocardial infarction by administration of isoprenaline hydrochloride (85 mg/kg), sc, on two consecutive days. An equal number of rats were given saline to serve as control. Heart specimens were taken for macroscopic and microscopic examination after 1 day, 5 days, 12 days and 21 days, following myocardial infarction. Ibuprofen pre-treatment caused a significant increase in infarct size at all the intervals studied (P less than 0.01), indicating that ibuprofen exerted a harmful effect in increasing the size of experimental myocardial infarction.

Animals↗
PubMed1991

Pharmacokinetics, neuromuscular effects, and biodisposition of 3-desacetylvecuronium (Org 7268) in cats.

The pharmacokinetics, biodisposition, and neuromuscular blocking properties of 3-desacetylvecuronium were studied in 17 adult cats. Animals were divided into three groups: five cats with kidney failure induced by bilateral ligation of the renal pedicles, six cats with galactosamine-induced fulminant hepatitis, and six control cats. An intravenous bolus of 300 micrograms.kg-1 of 3-desacetylvecuronium was rapidly injected into the jugular vein. Arterial blood, urine, and bile samples were collected at regular intervals for 6 h in control cats and for 8 h in cats with kidney or liver failure. The liver was excised for analysis at the end of the experiment. In cats with renal failure, 3-desacetylvecuronium pharmacokinetic and pharmacodynamic variables did not differ from those in control cats. In cats with liver failure, plasma clearance was significantly less and mean residence time greater than in control cats (2.8 +/- 0.6 vs. 14.1 +/- 6.5 ml.kg-1.min-1 and 334 +/- 225 vs. 49 +/- 29 min, mean +/- SD, respectively). Volume of distribution at steady state in cats with liver failure and in control cats was not different. Also, in cats with liver failure, the duration of action and recovery index of 3-desacetylvecuronium was significantly greater than in control cats (168 +/- 62 vs. 82 +/- 32 min, and 39 +/- 19 vs. 10 +/- 4 min, respectively). Onset time of neuromuscular blockade was similar in all three groups. Total recovery of 3-desacetylvecuronium, for all three groups, in urine, bile, and liver was 90 +/- 11% (mean +/- SD). In control cats, 70 +/- 18% of 3-desacetylvecuronium was recovered in bile and liver and 19 +/- 14% in urine. No 3,17-bidesacetylvecuronium (a putative 3-desacetylvecuronium metabolite) was detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Hemato-clinical changes in phenylhydrazine-induced acute hemolytic anaemia in calves.

Acute anaemia was induced in calves aged 1 week, using the oxidant chemical phenylhydrazine-hydrochloride (PHH). The hematoclinical responses to graded doses were evaluated. Mild anaemia was observed with the 60 mg/kg body weight (B.W.) dose. The 100 mg/kg B.W. dose was too toxic. The sublethal 80 mg/kg B.W. dose produced the desired type of hemolytic anaemia, the peak of which being observed on d 4 post-injection (p.i.). Hemolytic anaemia was evidenced by hemoglobinaemia and hemoglobinuria. The acute toxicity symptoms lasted for about 30 min. Thereafter, the animals appeared to overcome the stress. In general, increases in pulse and respiration coincided with progress of the hemolytic syndrome. Peak response occurred 48 to 60 h p.i.

Acute Disease↗
PubMed1991

Pathomorphological changes in calf erythrocytes during phenylhydrazine-induced acute hemolytic anaemia.

In acute hemolytic anaemia of calves induced with phenylhydrazine-hydrochloride, accentuated degenerative changes in circulating erythrocytes occurred on the 5th d post-injection. Marked anisocytosis and poikilocytosis were observed. Crenated cells, acanthocytes (star-shaped cells), dacrocytes (tear drop cells), bite cells, and schistocytes predominated. Heinz bodies were the cytoplasmic hallmark of hemolytic anaemia. The regenerative nature of anaemia was evidenced by early appearance of reticulocytes in peripheral blood.

Acute Disease↗
PubMed1990

Cardiac injuries--a clinical and autopsy profile.

One hundred two patients sustaining cardiac injuries over a 4-year period were analysed to highlight the natural history of the cardiac injuries. There were 45 blunt, 36 stab, and 21 gunshot injuries. The injury involved the ventricle in 85, atrium in seven, pulmonary artery in five cases, and resulted in crush injury to the heart in the remaining five cases. Thirty-three patients (32.3%) died on the scene and 58 (56.9%) died during the transportation. Only 11 patients (10.8%) reached the hospital alive, and ten of these patients survived following thoracotomy and repair of the cardiac injury. The factors influencing the natural course of cardiac injury were analysed: 2.2% of patients with blunt cardiac trauma reached the hospital alive compared to 19.4% with stab and 14.3% with gunshot injuries; ventricular injuries had a greater prehospital mortality compared to atrial or pulmonary artery injuries; 11.3% of patients sustaining injury to right ventricle reached the hospital alive compared to 3% of those with left ventricular injuries. These data emphasize the need for rapid transport, immediate recognition, and aggressive surgical management, to make a favourable impact on the natural history of cardiac injuries.

Adolescent↗
PubMed1989

Surgical experience with diseases of the tricuspid valve. Cross-sectional and Doppler echocardiographic evaluation following DeVega's repair.

Seventy-eight patients undergoing mitral valve surgery with or without replacement of the aortic valve also underwent procedures on the tricuspid valve over a period of 10 years. All patients were in functional class III or IV preoperatively. The procedures were performed in all patients with organic disease of the tricuspid valve (N = 44) and in those with moderate or severe functional tricuspid valvar regurgitation (N = 34). Seventy-one patients underwent DeVega's annuloplasty with or without commissurotomy. The overall mortality was 11.5%. 65 long-term survivors were followed up for a period of 6 months to 10 years (mean 5.3 years). Sixty-three patients were in functional class I or II at the last follow-up. Six patients had clinical evidence of mild to moderate tricuspid regurgitation. Regression of cardiomegaly (as judged by the chest radiograph and right ventricular hypertrophy seen in the electrocardiogram) was evident in most cases. Fifty-one of 54 patients evaluated by cross-sectional echocardiography were reported to have a functionally normal tricuspid valve. Doppler echocardiography in 28 patients showed no significant tricuspid regurgitation or stenosis in 26 patients. Eleven consecutive patients undergoing DeVega's annuloplasty were studied prospectively with pre- and postoperative Doppler echocardiography. Good correlation existed between right ventricular systolic pressures predicted by Doppler with those obtained preoperatively at cardiac catheterization. Postoperative Doppler echocardiography in these 11 patients showed complete restoration of competence of the tricuspid valve as well as normalisation of the right ventricular systolic pressure in 10 patients.

Adult↗
PubMed1989

Anti-arthritic activity of boswellic acids in bovine serum albumin (BSA)-induced arthritis.

The effect of boswellic acids on bovine serum albumin (BSA)-induced arthritis in rabbits was studied. Oral administration of boswellic acids (25, 50 and 100 mg/kg/day) significantly reduced the population of leucocytes in a BSA-injected knee and changed the electrophoretic pattern of the synovial fluid proteins. The local injection of boswellic acids (5, 10 and 20 mg) into the knee 15 min prior to BSA challenge also significantly reduced the infiltration of leucocytes into the knee joint, reduced the infiltration of leucocytes into the pleural cavity and inhibited the migration of PMN in vitro. The leucocyte-inhibitory activity of boswellic acids was not due to its cytotoxic effect. The boswellic acids did not show any detergent or surfactant properties.

Animals↗
PubMed1989

Hypotensive activity of 8,24-euphadien-3 beta-ol (euphol).

8,24-Euphadien-3 beta-ol (euphol) on i.v. administration was found to exhibit a hypotensive activity in normotensive anesthetised dogs and rats which varied from a slight to a marked degree depending upon the dose range. Euphol inhibited various autonomic pressor and depressor responses. The hypotensive effect was not affected in dogs pretreated with atropine, antistine, and beta-blockers and in bilaterally vagotomised and carotid sinus denervated animals. The fall in blood pressure was enhanced in spinal transected and eviscerated dogs and after ganglion blockade with hexamethonium. Localisation of euphol to central cardiovascular loci displayed no effect on blood pressure. The LD50 in mice was found to be 1500 mg/kg i.p. and greater than 2 g/kg by the oral route.

Animals↗