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Biomedical subjects

H Weisman

Publications and source records attributed to H Weisman.

At least 19 recordsLinked to original sources
PubMed1996

Effect of sinus denervation and vagotomy on c-fos expression in the nucleus tractus solitarius after exposure to CO2.

Exposure to hypercapnia and electrical stimulation of the carotid sinus nerve (CSN) has been shown to induce c-fos expression in several brain stem regions including the nucleus tractus solitarius (NTS). To test whether the labeled neurons were activated directly by hypercapnia or secondarily via the carotid bodies (sinus nerve), adult rats were exposed to either air or 14-16% CO2 for 1 h. Experiments were done on eight groups: (1) exposure to air, (2) exposure to CO2, (3) chronic CSN denervation/CO2, (4) chronic unilateral CSN denervation/CO2, (5) chronic sham CSN denervation/CO2, (6) anesthetized/CO2, (7) anesthetized and acute vagotomy/CO2, and (8) premedicated with morphine, 10 mg s.c., 20 min before exposure to CO2. After exposure to CO2 or air the rats were anesthetized, perfused with 4% paraformaldehyde and the brains processed for immunohistochemical staining for c-fos protein using the PAP (i.e. peroxidase anti-peroxidase) technique. Labeled neurons in the area of the NTS in every second 50- "mu"m section were counted and their position plotted using a microscope and camera lucida attachment. Rats exposed to CO2 had a significantly greater number of labeled neurons in the NTS than those exposed to air. Other interventions, such as CSN denervation, surgery, anesthesia, vagotomy or injection of morphine did not significantly affect the level of c-fos expression in rats exposed to hypercapnia, indicative of central stimulation rather than secondary peripheral input. These responsive neurons may be part of a widespread central chemoreceptive complex.

Animals↗
PubMed1996

A double-blind trial of haloperidol, chlorpromazine, and lorazepam in the treatment of delirium in hospitalized AIDS patients.

OBJECTIVE: The purpose of this study was to examine the efficacy and side effects of haloperidol, chlorpromazine, and lorazepam for the treatment of the symptoms of delirium in adult AIDS patients in a randomized, double-blind, comparison trial. METHOD: Nondelirious, medically hospitalized AIDS patients (N = 244) consented to participate in the study and were monitored prospectively for the development of delirium. Patients entered the treatment phase of the study if they met DSM-III-R criteria for delirium and scored 13 or greater on the Delirium Rating Scale. Thirty patients were randomly assigned to treatment with haloperidol (N = 11), chlorpromazine (N = 13), or lorazepam (N = 6). Efficacy and side effects associated with the treatment were measured with repeated assessments using the Delirium Rating Scale, the Mini-Mental State, and the Extrapyramidal Symptom Rating Scale. RESULTS: Treatment with either haloperidol or chlorpromazine in relatively low doses resulted in significant improvement in the symptoms of delirium as measured by the Delirium Rating Scale. No improvement in the symptoms of delirium was found in the lorazepam group. Cognitive function, as measured by the Mini-Mental State, improved significantly from baseline to day 2 for patients receiving chlorpromazine. Treatment with haloperidol or chlorpromazine was associated with an extremely low prevalence of extrapyramidal side effects. All patients receiving lorazepam, however, developed treatment-limiting adverse effects. Although only a small number of patients had been treated with lorazepam, the authors became sufficiently concerned with the adverse effects to terminate that arm of the protocol early. CONCLUSIONS: Symptoms of delirium in medically hospitalized AIDS patients may be treated efficaciously with few side effects by using low-dose neuroleptics (haloperidol or chlorpromazine). Lorazepam alone appears to be ineffective and associated with treatment-limiting adverse effects.

AIDS Dementia Complex↗
PubMed1995

A chimeric IgG4 monoclonal antibody directed against CD18 reduces infarct size in a primate model of myocardial ischemia and reperfusion.

OBJECTIVES: This study attempted to determine whether neutrophil sequestration in reperfused myocardium can be inhibited and infarct size reduced by treatment with a chimeric, monoclonal IgG4 antibody (CLB54) directed against CD18 in a primate model of acute myocardial ischemia and reperfusion. BACKGROUND: Reperfusion injury, in part mediated by neutrophils, may limit the potential benefit of reestablishing infarct-related artery patency in patients with acute myocardial infarction. METHODS: Nineteen closed-chest baboons (10 control, 9 treated with CLB54) had the left anterior descending coronary artery occluded for 90 min, followed by 4 h of reflow. CLB54 (mean [+/- SD] 11 +/- 2 mg/kg body weight) or saline solution was administered intravenously 20 min before reflow. Coronary flow was determined using radiolabeled microspheres, infarct size by triphenyltetrazolium chloride staining, global and regional ventricular function by contrast ventriculography and neutrophil accumulation by a myeloperoxidase assay. RESULTS: Risk region size was the same in both groups. CLB54 treatment reduced infarct size expressed as a percent of the risk region from 41 +/- 20% in the saline-treated group to 19 +/- 17% in the CLB54-treated group (p < 0.02). This was associated with diminished myeloperoxidase activity and greater postreperfusion coronary flow in the risk region in CLB54-treated than in control baboons. Ejection fraction declined to the same extent in both groups, whereas anterior wall regional cord shortening was better preserved in CLB54-treated baboons. CONCLUSIONS: Inhibition of neutrophil sequestration with CLB54 administered before reperfusion reduces infarct size, preserves ischemic zone microvascular perfusion and minimizes the decline of regional wall motion.

Animals↗
PubMed1994

Chimeric 7E3 prevents carotid artery thrombosis in cynomolgus monkeys.

BACKGROUND AND PURPOSE: We compared the current antithrombotic strategy of antiplatelet therapy with aspirin, and anticoagulant therapy with heparin, with a specific genetically engineered chimeric antibody (c7E3 Fab) directed against the human glycoprotein IIb/IIIa receptor in an animal model of arterial thrombosis. METHODS: Anesthetized cynomolgus monkeys (Macaca fascicularis) were instrumented for monitoring of arterial blood pressure, heart rate, and carotid artery flow velocity. Animals were treated with saline (n = 6), aspirin (25 mg PO daily for 3 days; n = 6), heparin (100 U/kg i.v. plus infusion adjusted to maintain activated partial thromboplastin time at 2 to 3 times baseline; n = 6), aspirin plus heparin (as administered separately, n = 6), or c7E3 Fab (0.10 mg/kg i.v., n = 7; 0.15 mg/kg i.v., n = 6; 0.20 mg/kg i.v., n = 6; 0.25 mg/kg i.v., n = 6). Thrombus formation via anodal electrolytic stimulation (100 microA) to the intimal surface of the right carotid artery was initiated 15 minutes after drug administration and continued for 180 minutes. Electrolytic injury to the left carotid artery began 210 minutes after drug administration and continued for 180 minutes. Whole blood cell counts, glycoprotein IIb/IIIa receptor blockade, ex vivo platelet aggregation, template bleeding time, and activated partial thromboplastin time were assessed at various time points throughout the experimental protocol. RESULTS: Hemodynamic and hematologic parameters were comparable among groups at baseline. Treatment with c7E3 Fab inhibited ex vivo platelet aggregation, increased bleeding time, decreased thrombus weight, and increased time to occlusion in a dose-dependent manner in both vessels. Treatment with aspirin, heparin, or the combination of aspirin plus heparin was ineffective for the prevention of carotid artery thrombosis in this model. CONCLUSIONS: Inhibition of the platelet glycoprotein IIb/IIIa receptor with c7E3 Fab was found to be safe and effective for the prevention of primary thrombus formation, whereas treatment with either aspirin or heparin or the combination of the two agents failed to protect against occlusive thrombus formation in cynomolgus monkeys.

Abciximab↗
PubMed1993

Hepatic blood volume responses and compliance in cats with long-term bile duct ligation.

Hepatic capacitance responses were compared in sham-operated and 14-day bile duct-ligated cats under pentobarbital anesthesia. Both groups were subjected to splenectomy and had the anterior hepatic nerve plexus sectioned to allow stimulation; the posterior plexus was intact. Blood volume compensation for hemorrhage was reduced in the bile duct ligation group compared with the control group: The liver compensated for 20.1% and 10.6% of blood loss, respectively. Portal hypertension did not exist and hepatic compliance was unaltered despite the presence of severe biliary hyperplasia, portal tract distortion and fibrosis. The capacitance responses to hemorrhage in the bile duct ligation group were accounted for entirely by a passive compliant response to reduced portal pressure, whereas the sham surgery group showed an additional active component. Responses of liver volume and venous resistance to norepinephrine were normal, but responses to nerve stimulation were reduced. The nerve dysfunction was not universal; reflex arterial blood pressure response to carotid occlusion was normal. The data suggest that hepatic blood volume responses to hemorrhage is mediated by passive compliant responses to reduced portal pressure (stressed volume) and active responses (unstressed volume) to nerve stimulation but that long-term bile duct ligation produces selective hepatic neuropathy resulting in loss of the active component.

Animals↗
PubMed1993

Profound inhibition of platelet aggregation with monoclonal antibody 7E3 Fab after thrombolytic therapy. Results of the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) 8 Pilot Study.

OBJECTIVES: This study was undertaken to establish evidence for physiologic activity and to study the safety of murine-derived monoclonal antibody 7E3 Fab (m7E3 Fab) in patients receiving recombinant tissue-type plasminogen activator (rt-PA). BACKGROUND: Platelet aggregation is believed to be a significant factor in the failure of pharmacologic reperfusion. By binding to the glycoprotein IIb/IIIa receptor, m7E3 Fab inhibits platelet aggregation and has been shown experimentally to decrease the time required for lysis and to prevent reocclusion. However, the safety of profound platelet inhibition after thrombolysis for acute myocardial infarction has not been tested in humans. METHODS: Sixty patients receiving rt-PA, aspirin and heparin for acute myocardial infarction received m7E3 Fab bolus injections in ascending doses at 3, 6 and 15 h after initiation of the thrombolytic infusion. Ten patients treated with rt-PA but not m7E3 Fab were studied as control subjects. RESULTS: Receptor site blockade and inhibition of platelet aggregation to 20 mumol/liter adenosine diphosphate were maximal at a dose of 0.25 mg/kg body weight of m7E3 Fab. Fifteen (25%) m7E3 Fab-treated patients and five (50%) control patients had major bleeding; eight of these events in seven m7E3 Fab-treated patients and one in a control patient occurred at the time of aortocoronary bypass surgery. Recurrent ischemia occurred in eight (13%) m7E3 Fab-treated patients and two (20%) control subjects. Coronary angiography was performed in 43 patients; the infarct-related coronary artery was patent in 5 of 9 (56%) control patients and 34 (92%) of 37 patients receiving m7E3 Fab. CONCLUSIONS: Profound inhibition of platelet aggregation after thrombolysis was associated with bleeding rates comparable to those in control patients and a low rate of recurrent ischemia. The combination of m7E3 Fab and rt-PA, heparin and aspirin appears to be a promising and safe combination that should be evaluated in further studies of patients with acute myocardial infarction.

Aged↗
PubMed1992

Effect of U-50,488H on the contractile response of cardiomyopathic hamster ventricular myocytes.

We examined the effects of a selective kappa opioid receptor agonist (U-50,488H) on the contractile properties of single ventricular myocytes from 127 day old control (F1B) and cardiomyopathic (BIO 14.6) hamsters. Myocytes in bicarbonate buffered solution with 1.5 mM [Ca2+] were electrically stimulated with field electrodes in the bath. Length changes were monitored via myocyte edge tracking. Twitch amplitude and the velocity of cell shortening were less in the cardiomyopathic hamster myocytes than in age-matched hamsters (P less than or equal to 0.05). There was a concentration-dependent effect of U-50,488H (0.1-20 microM) to decrease twitch amplitude and shortening velocity in both control and cardiomyopathic myocytes (P less than or equal to 0.001). In cells loaded with the Ca2+ indicator indo-1 the negative inotropic action of U-50,488H was associated with a decreased indo-1 fluorescence transient amplitude. There was no difference in the negative inotropic effect of U-50,488H on control and cardiomyopathic cells. Thus, the CM hamster does not demonstrate a different contractile response to U-50,488H.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1986

Localization of intrahepatic portal vascular resistance.

The pressure drop from the portal vein to the vena cava occurs primarily across a postsinusoidal site localized to a narrow segment (less than 0.5 cm) of hepatic veins (roughly 1.5 mm diam) in the anesthetized cat. Portal venous pressure (PVP = 8.9 +/- 0.3 mmHg) and lobar hepatic venous pressure (LVP = 8.7 +/- 0.4 mmHg) are insignificantly different, and pressure changes imposed from the presinusoidal or postsinusoidal side are equally transmitted to both pressure sites. Several types of experiments were done to validate the LVP measurement. The portal vein, hepatic sinusoids, and hepatic veins proximal to the resistance site are all under a similar pressure. Previously reported calculations of hepatic vascular resistance are in error because of incorrect assumptions of sinusoidal pressure and localization of the portal resistance site as presinusoidal. Stimulation of hepatic sympathetic nerves for 3 min caused LVP and PVP to increase equally, showing that the increased "portal" resistance is postsinusoidal across the same region of the hepatic veins that was previously localized as the site of resistance in the basal state.

Animals↗
PubMed1983

Application of an automatic electronic image analyzer to the measurement of myocardial extracellular space.

The volume of the rat myocardial extracellular compartment was determined by electronic image analysis (Zeiss Micro-Videomat) and compared with values obtained by point-counting on the same histological micrographs. The data suggest that the results obtained by the two methods may be expected to be approximately within 10% of each other. The subjective component of the morphometry was not entirely eliminated due to some heterogeneity in the staining of the histological sections. Until the deficiencies in staining homogeneity are eliminated, the main advantage of the image analysis compared to point-counting will be limited to a greater labor efficiency.

Animals↗
PubMed1981

Reduction in the severity of myocardial infarction by sulfinpyrazone.

The effect of sulfinpyrazone (Anturane) on the extent of myocardial lesions caused by coronary ligation or isoproterenol, 5 mg/kg subcutaneously, was determined in the rat. Treatment was with sulfinpyrazone, 15 mg/kg twice daily for 5 days before the cardiac insult, or 21 days after the insult, or both. Pretreatment with sulfinpyrazone reduced isoproterenol-induced lesions by 42%. Treatment after isoproterenol had no significant effect. With coronary ligation, treatment before or after operation significantly reduced the size of infarct, pretreatment by 42%, post-treatment by 33%. The results provide evidence that sulfinpyrazone may have a clinically useful protective effect in individuals at risk of cardiac ischemia, as suggested in the Anturane Reinfarction Trial.

Animals↗