Blood brain barrier in meningitis.
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Biomedical subjects
Publications and source records attributed to B Sharma.
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Cyclophosphamide (CY) has been shown to modulate a number of immune responses. In the present study, we have examined the effect of CY on human natural killer (NK) cells in vitro. Lymphocytes from six normal volunteers were cultured alone or with CY in the medium containing human AB plasma, and their cytotoxicity was assessed against cells of K562. The results demonstrated that lymphocytes when cultured with CY had 154 to 333% increase in NK cell activity as compared to lymphocytes that were cultured in the absence of CY. Similarly, CY markedly boosted the cytotoxic activity of lymphocytes from two healthy donors against cells from cultured B-leukemia 3163. Maximal augmentation occurred in cultured lymphocytes that expressed low levels of effector NK activity. Lymphocytes from 13 of 15 children with acute leukemia in remission when cultured alone had no reactivity to autologous leukemia cells. In the presence of CY, lymphocytes from eight of 15 of these patients developed cytotoxicity against autologous leukemia cells. CY was effective in augmenting NK cell activity at concentrations ranging from 7.5 to 60 micrograms/ml. Maximal potentiation of NK cell activity was induced after 8 hr of treatment with CY, although the increase in NK activity was started within 2 hr of incubation with CY. CY-activated NK cells were found in glass wool- and nylon wool-nonadherent cells. Treatment of lymphocytes with CY did not increase the extracellular levels of interferon. The results of this study demonstrate that CY can activate NK cells in vitro. The possible mechanisms of CY-induced augmentation of NK cell activity are discussed.
Diastolic left ventricular (LV) properties were studied at rest and during spontaneous angina pectoris during cardiac catheterization in 10 patients with severe coronary artery disease. During spontaneous angina there was a significant increase in LV filling pressures through diastole. The right ventricular end-diastolic pressure was measured at rest and during spontaneous angina in 7 of 10 patients and showed an increase from 7 +/- 3 to 10 +/- 4 mm Hg (mean +/- SD) (p less than 0.02). The T index (a measure of LV isovolumic relaxation) at rest was 51 +/- 17 ms and increased during angina to 58 +/- 12 ms (p less than 0.01), indicating an early diastolic relaxation dysfunction. Frame-by-frame LV volumes and corresponding pressures were analyzed from 3 consecutive beats in 5 of 10 patients. In 4 of these 5, the pressure-volume loop shifted upward and slightly to the right during angina. There was a significant increase in the rate of filling during mid-diastole with angina. Left atrial stroke work index increased by 35% during angina, suggesting an increased work load on the left atrium to maintain late diastolic filling.
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.