Biomedical subjects
Publications and source records attributed to B Sharma.
Vasoplasty was performed in 40 cases by the flap technique; the patency rate was 79% and the pregnancy rate 34%. The method produced acceptable results almost as good as those achieved by microsurgery but without the need for expensive apparatus and long training.
Cell-free extracts (CFE) from cultured human tumor cells, when used to sensitize lymphocytes, were capable of inducing distinct lymphocyte-mediated cytotoxicity (LMC) at low dose and had relatively low or no activity at a high dose. The higher dose of CFE suppressed markedly the induction of LMC when added to the mixed lymphocyte tumor cell cultures. The ability to induce LMC was associated most with 10,000 g fractions. All fractions, 1,000, 20,000 and 100,000 g, were able to suppress the induction of LMC, but 100,000 g fractions had the most suppressive activity. The supernatants of 100,000 g fractions were only slightly suppressive. Lymphocytes activated with tumor cell fractions were also cytotoxic to K-562 cells.
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The hemodynamic effects of dopamine (DPM) and dobutamine (DBM) were compared in 13 patients with acute cardiogenic circulatory collapse. All patients presented with acute pump failure and inadequate systemic perfusion, and most were hypotensive. Nine patients had an acute myocardial infarction (AMI); the other four patients had an acute decompensation of a previously stable ischemic cardiomyopathy, and presented with a low-output syndrome in the absence of documented AMI. Patients were studied with a randomized single crossover design using each patient as his own control. Both drugs were given at doses of 2.5, 5, and 10 micrograms/kg/min for periods of 10 minutes at each dose while hemodynamics were monitored. No other vasoactive drugs were used during the study. Because of advanced age or severe peripheral vascular disease, no patient was considered suitable for intra-aortic balloon counterpulsation. There were no significant differences between the two drugs with regard to heart rate, mean-arterial pressure, systemic vascular resistance, stroke work index, or mean right atrial pressure. DBM improved stroke index and cardiac index significantly (p less than 0.05) more than DPM at doses of 5 micrograms/kg/min. DPM increased left ventricular filling pressure (LVFP) more than DMB at 5 micrograms/kg/min (p less than 0.001) and at 10 micrograms/kg/min (p less than 0.05). Although both DPM and DBM are useful in acute cardiogenic circulatory collapse, there appear to be important differences in their effect on LVFP and in the mechanisms whereby they increase blood pressure.
Pharmacokinetic studies on antipyrine, chloramphenicol, acetaminophen, and sulphadiazine have been carried out in infants and children suffering from protein-energy malnutrition (PEM). Increased antipyrine plasma half-life in PEM indicated altered mixed oxidative microsomal enzyme activity in hepatocytes. Chloramphenicol was absorbed (ka) as well as eliminated (ke) at slower rates in PEM. The net result was that the comparative bioavailability of the drug was higher in PEM as compared to the control. Observations were similar in the case of sulphadiazine. The rate of absorption (ka) of acetaminophen was not affected in children with PEM, but the elimination rate constant was slower and plasma half-life prolonged. Noticeable improvement was observed within 6-8 weeks of nutritional rehabilitation with respect to chloramphenicol, antipyrine, and acetaminophen pharmacokinetics.
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Fourteen patients with refractory congestive heart failure (CHF) were given a single oral dose ranging from 5 to 30 mg of the new sympathomimetic drug pirbuterol. Hemodynamic measurements and plasma pirbuterol levels were obtained at control and then serially for 6 hours following drug administration. The optimal pirbuterol dose range was determined to be 20 to 30 mg. Ten patients received 20 to 30 mg pirbuterol. In this group cardiac index was significantly increased (1.9 to 2.6 L/min/m2, p less than 0.001). Pulmonary artery wedge pressures fell significantly (24 to 20 mm Hg, p less than 0.02). Decreases were also noted in mean pulmonary artery pressure (36 to 31 mm Hg, p less than 0.02), aortic diastolic pressure (71 to 65 mm Hg, p less than 0.05), systemic vascular resistance (1782 to 1201 dynes. sec. cm-5, p less than 0.001), and pulmonary vascular resistance (265 to 175 dynes.sec.cm-5, less than 0.001). Systolic and mean aortic pressure and heart rate showed no significant change from control. Hemodynamic effects persisted for 5 hours. Pirbuterol was clinically well tolerated. The mechanism of action is unclear at this time, but both inotropic and vasodilator effects are possible. Pirbuterol orally has a marked and prolonged salutary hemodynamic effect and offers promise in CHF treatment.
Observations made in detecting left ventricular thrombus with two dimensional echocardiography in 25 patients are reviewed. In 20 patients thrombus was documented on angiography, surgery postmortem examination or serial two dimensional echocardiographic findings; in the remaining five patients two dimensional echocardiographic findings of thrombus were unequivocal. In all 25 patients wall motion abnormalities ranging from hypokinesia to frank dyskinesia were present at the site of the thrombus. Twenty-three patients had an apical thrombus; two had thrombus adjacent to the inferior wall. Clear delineation of the endocardium and thrombus margin was considered essential to the correct diagnosis of thrombus. Both intracavitary motion of the thrombus margin and a layering effect were noted infrequently although they were of benefit in identifying an intracardiac mass as thrombus. In addition, serial evaluations were helpful in establishing the correct diagnosis. False positive diagnoses can be minimized if one understands certain technical limitations of this method and correctly identifies apical structures that are not thrombi. Axial and lateral resolution problems inherent with this technique can produce intracavitary echoes that may simulate thrombi. In addition, normal or pathologic structures at the apex may also simulate thrombi. These structures include the papillary muscles, muscular trabeculae, chordal structures and tangential information from normal myocardium. Varying the sector orientation or acoustic window, or both, will aid in correctly identifying these structures and distinguishing them from left ventricular thrombi.
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6 children with protein calorie malnutrition (PCM) and 5 control children received a single dose of sulfadiazine (25 mg/kg body weight). Absorption rate constant in the control group was 0.735 +/- 0.058 h-1 and in PCM 0.519 +/- 0.03 h-1. Peak blood levels of the drug were similar in both groups. However, the time to reach the peak was shorter in the control than in the PCM group. Elimination rate constant and half life of the drug were 0.0233 +/- 0.0026 h-1 and 31.78 +/- 3.82 h, respectively, in the PCM group and 0.0332 +/- 0.0022 h-1 and 21.27 +/- 1.51 h, respectively, in the control group. These values differ significantly from each other. The area under the blood concentration-time curve was more than double in the PCM group as compared to the control group. Urinary excretion of the drug in 48 h was significantly more in control (19.3 +/- 1.4 mg/kg body weight) in comparison to the PCM group (13.6 +/- 1.7 mg/kg body weight). However, the free drug concentration in urine/kg body weight was not altered in the PCM group. There was a significant decrease in quantity of acetylated drug in the PCM group as compared to the controls. In view of these observations, therapy with sulfadiazine in children suffering from PCM requires reconsideration.
Between 1975 and 1979 we performed coronary arteriography on 15 patients with end-stage renal failure and clinical evidence of severe ischemic heart disease. One patient died after the procedure of severe pump failure. Ten patients subsequently received coronary-artery bypass grafts, and two of these patients also received mitral-valve replacement. One patient, a diabetic, died of sepsis after surgery. Eight of the nine surviving patients, including the two patients who had undergone mitral-valve replacement, are markedly improved as a result of surgery. Our experience indicates that these patients can undergo angiography and coronary-artery bypass surgery at an increased but acceptable risk, provided dialysis is done before and after cardiac catheterization and surgery to control extracellular volume overload and hyperkalemia. The operation benefits patients with end-stage renal failure and severe ischemic heart disease by relieving angina and improving their level of activity. It is unclear whether survival is improved for these patients.
Eighteen patients with ischemic heart disease who underwent left ventricular aneurysmectomy (LVA) and concomitant mitral valve replacement (MVR) for severe mitral regurgitation during 1973-1978 were identified. Eleven patients (61%) underwent aortocoronary bypass procedures (CABG) at the same operation. All patients had New York Heart Association class III or IV symptoms of congestive heart failure; six (33%) had disabling angina pectoris and four (22%) had had life-threatening ventricular tachycardia. Surgical mortality was 11%. The survival rate at 2 and 3 years was 80% and 57%, respectivey, with a mean follow-up of 21 months (range 4-56 months). At follow-up all patients had improved symptomatically by at least one functional clas; four patients were class II and six were class 1. The mean values (+/ SEM) for preoperative cardiac index, left ventricular end-diastolic pressure and ejection fraciton were 2.0 +/- 0.1 l/min/m2, 22 +/- 2.3 mm Hg, and 30 +/- 3.5%, respectively. Postoperative right-heart catheterization in seven patients revealed no difference between preoperative and postoperative resting cardiac index and pulmonary wedge pressure, although all seven patients claimed significant improvement. Thus, although resting hemodynamics may not be altered, combined LVA, MVR and CABG can be performed with acceptable surgical risk in these seriously ill patients and can provide excellent symptomatic improvement with good long-term survival.
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During the years 1974 of 1976, 514 patients with prehospital cardiopulmonary arrest were brought to the Hennepin County Medical Center (HCMC) Emergency Department. Of these, 344 patients (67%) were either dead on arrival or died in the emergency department despite efforts at resuscitation. The remaining 170 patients were admitted to the coronary care unit. Eighty-seven patients (51%) died in the coronary care unit, primarily from uncontrolled rhythm disturbances and/or cardiogenic shock. The remaining 83 patients (16% of the total group, 49% of those admitted to the hospital) were discharged alive from HCMC. In this group, 49 patients of the 83 long-term survivors were ambulatory with full mental function when discharged. The remaining 34 patients were trnasferred to chronic care facilities for medical treatment of on-going problems. Of the 49 ambulatory patients, satisfactory data for follow-up was obtained on 47. Their mortality rate was 15% in the first year and 50% in the second, primarily from sudden death syndrome.