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Biomedical subjects

M S Pessin

Publications and source records attributed to M S Pessin.

At least 19 recordsLinked to original sources
PubMed1992

Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke.

An open angiography-based, dose rate escalation study on the effect of intravenous infusion of recombinant tissue plasminogen activator (rt-PA) on cerebral arterial recanalization in patients with acute focal cerebral ischemia was performed at 16 centers. Arterial occlusions consistent with acute ischemia in the carotid or vertebrobasilar territory in the absence of detectable intracerebral hemorrhage were prerequisites for treatment. After the 60-minute rt-PA infusion, arterial perfusion was assessed by repeat angiography and computed tomography scans were performed at 24 hours to assess hemorrhagic transformation. Of 139 patients with symptoms of focal ischemia, 80.6% (112) had complete occlusion of the primary vessel at a mean of 5.4 +/- 1.7 hours after symptom onset. No dose rate response of cerebral arterial recanalization was observed in 93 patients who completed the rt-PA infusion. Middle cerebral artery division (M2) and branch (M3) occlusions were more likely to undergo recanalization by 60 minutes than were internal carotid artery occlusions. Hemorrhagic infarction occurred in 20.2% and parenchymatous hematoma in 10.6% of patients over all dose rates, while neurological worsening accompanied hemorrhagic transformation (hemorrhagic infarction and parenchymatous hematoma) in 9.6% of patients. All findings were within prospective safety guidelines. No dose rate correlation with hemorrhagic infarction, parenchymatous hematoma, or both was seen. Hemorrhagic transformation occurred significantly more frequently in patients receiving treatment at least 6 hours after symptom onset. No relationship between hemorrhagic transformation and recanalization was observed. This study indicates that site of occlusion, time to recanalization, and time to treatment are important variables in acute stroke intervention with this agent.

Acute Disease↗
PubMed1992

Intracranial hemorrhage after coronary thrombolysis with tissue plasminogen activator.

PURPOSE AND METHODS: We analyzed the clinical, laboratory, and radiologic data in nine patients who sustained an intracranial hemorrhage (ICH) after receiving intravenous recombinant tissue plasminogen activator (rt-PA) and heparin for treatment of acute myocardial infarction (MI). Our purpose was to delineate the clinical and radiologic features of the ICHs, as well as to determine their potential risk factors and mechanisms. RESULTS: Among 1,700 patients with an acute MI treated with an investigational two-chain rt-PA, duteplase (Burroughs Wellcome Co., Research Triangle Park, NC), nine (0.53%) developed symptomatic ICH. Neurologic symptoms occurred between 7 and 96 hours after onset of rt-PA therapy. All patients received heparin concomitantly for prevention of coronary reocclusion. The activated partial thromboplastin times (aPTTs) in five of eight (63%) patients at onset of ICH were excessively prolonged (greater than two times control); hypofibrinogenemia occurred in only one of five (20%) patients tested; and thrombocytopenia was present in only one of the nine (11%) patients. Fibrin degradation products (FDPs) were elevated in all five patients tested. Minor hemorrhage (not requiring transfusion) outside the central nervous system occurred in five of the nine patients with ICH. The ICHs were often of lobar location and of moderate to large size. They occurred at multiple sites in three patients, and were fatal in four instances (44%). CONCLUSIONS: The incidence of ICH in this series was low, and consistent with figures reported from studies with alteplase in patients with acute MI. The mechanisms of these hemorrhages remain unclear; while hypofibrinogenemia was not a uniform finding, excessive prolongation of the aPTT and elevated FDPs may have contributed to the occurrence of ICH in some patients. Still unidentified local cerebrovascular factors may play an additional role in causing ICH. In order to further clarify the mechanisms of ICH in the setting of thrombolytic therapy, prospective data collection on probable risk factors for ICH in patients with acute MI treated with rt-PA will be required.

Aged↗
PubMed1992

Embolism from vertebral artery origin occlusive disease.

We report 10 patients with severe occlusive disease of the vertebral artery (VA) origin in the neck with intra-arterial embolism to the posterior circulation. The VA lesions in seven patients were complete occlusions, and three patients had severe atherostenosis. All patients had strokes in the vertebrobasilar territory. The most frequent recipient sites of intra-arterial embolism were the intracranial VA-posterior inferior cerebellar artery region (8), and the distal basilar artery (BA) and its superior cerebellar and posterior cerebral artery branches (7). Two patients had pontine infarction due to BA embolism. The most common clinical signs were due to cerebellar infarction. Atherosclerotic disease of the VA origin has features in common with disease of the internal carotid artery origin. Both have similar risk factors and demography, and each can cause strokes by intracranial intra-arterial embolism.

Aged↗
PubMed1992

Hemorrhagic transformation. The spectrum of ischemia-related brain hemorrhage.

Hemorrhagic transformation of ischemic cerebral injury occurs commonly in embolic strokes. The incidence, timing, and clinical consequences of hemorrhagic transformation are reviewed. Hemorrhagic complications resulting from heparin therapy and results from recent preliminary thrombolytic treatment trials are discussed.

Brain Ischemia↗
PubMed1991

Dissociation of protein kinase C activation and sn-1,2-diacylglycerol formation. Comparison of phosphatidylinositol- and phosphatidylcholine-derived diglycerides in alpha-thrombin-stimulated fibroblasts.

Diacylglycerols (DAGs) derived from phosphatidylcholine (PC) hydrolysis have been shown to activate protein kinase C (PKC) in vitro, but it is not known whether this event occurs in response to DAGs generated via agonist-induced PC hydrolysis in intact cells. In this report we have addressed this question directly, using alpha-thrombin stimulation of IIC9 fibroblasts. PKC activation in intact cells was assessed in two ways, by measuring: 1) PKC membrane association as determined by kinase activity and Western blot analysis and 2) the phosphorylation of an endogenous PKC substrate, an 80-kDa protein. Treatment with 500 ng/ml alpha-thrombin has been shown to stimulate both phosphoinositide and PC hydrolysis, whereas treatment with 100 pg/ml alpha-thrombin stimulates only PC breakdown. Using these two conditions, we show that DAG produced from phosphoinositide, but not PC hydrolysis, is associated with the activation of PKC.

Animals↗
PubMed1991

Changing attentional demands in left hemispatial neglect.

Seven variations of a letter cancellation test were used to examine how varying attentional demands affect hemispatial neglect in patients with right hemisphere lesions. While the 14 targets always remained in the same location, the number of distractors (zero, nine, 28, or 82) as well as their complexity (one letter or nine different letters) were varied. The percentage of targets canceled in the left hemispace was linearly related to the number of distractors. There were no differences between the complexity conditions. In a second study, the same 14 targets were presented but the distractors (zero, 14, or 41) were all placed on the right. Increasing the number of distractors on the right increased neglect on both sides of the space. Taken together, these results suggest that, while the limited attentional resources of the left hemisphere are biased toward the right hemispace, the absence of contralateral attentional demands allows these resources to be directed ipsilaterally.

Aged↗
PubMed1991

Carbachol stimulates a different phospholipid metabolism than nerve growth factor and basic fibroblast growth factor in PC12 cells.

We have examined 1,2-diglycerides (DGs) generated in PC12 cells in response to the muscarinic agonist carbachol and compared them with those generated in response to the differentiation factors nerve growth factor and basic fibroblast growth factor. Whereas carbachol stimulates a greater release of inositol phosphates, all three agonists generate similar levels of DGs. In this report, we have analyzed the molecular species of PC12 DGs generated in response to these three agonists. Additionally, we have analyzed the molecular species of PC12 phospholipids. The data indicate that 1) after 1 min of either nerve growth factor or basic fibroblast growth factor stimulation, DGs arise primarily from phosphoinositide hydrolysis; 2) in contrast, after 1 min of carbachol stimulation, DG are generated equally by both phosphoinositide and phosphatidylcholine hydrolysis; and 3) after 15 min of stimulation by any of these agonists, DGs are generated largely by phosphatidylcholine hydrolysis, with a smaller component arising from the phosphoinositides. These results suggest that at least part of the mechanism by which PC12 cells distinguish between different agonists is via alterations in phospholipid sources and kinetics of DG generation.

Animals↗
PubMed1991

Accelerated intracranial occlusive disease, oral contraceptives, and cigarette use.

We report clinical and angiographic features of accelerated intracranial occlusive disease resembling moyamoya vasculopathy in five young women who used oral contraceptives (OCs) and smoked cigarettes, but generally had no other obvious risk factors for cerebrovascular disease. Three women had been on OCs for at least 4 years, one woman each had been on OCs for 3 months and for 2 weeks. All five women had smoked cigarettes for at least eight pack-years. Intermittent and progressive multifocal cognitive, visual, motor, or sensory hemispheric symptoms and signs developed in all. All patients developed strokes, four preceded by transient ischemic attacks. Cerebral angiography demonstrated bilateral supraclinoid internal carotid artery stenosis in four patients and proximal posterior cerebral artery stenosis in one. Additional features included rete mirabile, telangiectasias, prominent lenticulostriate collaterals, and multifocal distal cerebral branch occlusions. Three had mild abnormalities of serum fibrinogen, antinuclear antibody, erythrocyte sedimentation rate, or CSF IgG. After discontinuing OCs and reducing cigarette use, four women have not had further strokes over a mean follow-up of approximately 5 years. In certain young women, clinical and angiographic features resembling moyamoya may develop with the use of OCs and cigarettes. We speculate that an immunologically mediated vasculopathy may explain, in part, this unusual cerebrovascular syndrome in otherwise healthy young women.

Adult↗
PubMed1991

Cerebrovascular complications after orthotopic liver transplantation: a clinicopathologic study.

We analyzed 55 autopsy cases in 1,357 patients undergoing orthotopic liver transplantation at the University of Pittsburgh and found that 13 (23.6%) patients had intracranial bleeding, and five (9%) had infarcts. Eight patients had bleeding localized to one intracranial compartment: intracerebral hemorrhage (three patients); subarachnoid hemorrhage (three patients); and subdural hematoma (two patients). Five patients had combinations of multiple sites of bleeding: three with subarachnoid hemorrhage-intracerebral hemorrhage, one with subarachnoid hemorrhage-intracerebral hemorrhage-subdural hematoma, and one with subdural hematoma-intracerebral hemorrhage. Coexistent CNS infections (fungal or bacterial) were associated with hemorrhagic infarcts and intracerebral hemorrhage in four patients. Cerebral embolism and hemorrhagic infarction from bacterial endocarditis occurred in one patient. Five patients died of intracranial bleeding. Severe coagulopathy was the major cause of intracranial bleeding and was associated with systemic bleeding in 12 patients. Significant systemic or metabolic complications were present in all patients and masked the focal signs of the intracranial process in more than one half.

Adult↗
PubMed1990

Molecular species analysis of mitogen-stimulated 1,2-diglycerides in fibroblasts. Comparison of alpha-thrombin, epidermal growth factor, and platelet-derived growth factor.

Recent studies have implicated the hydrolysis of phosphoinositides and phosphatidylcholine in agonist-stimulated events. The potent mitogen, alpha-thrombin, stimulates the generation of diglycerides in a biphasic and sustained manner in IIC9 fibroblasts (Wright, T. M., Rangan, L. A., Shin, H. S., and Raben, D. M. (1988) J. Biol. Chem. 263, 9374-9380). Using measurements of radiolabeled headgroup release and molecular species analysis, we previously determined that alpha-thrombin generates diglycerides through the hydrolysis of both the phosphoinositides and phosphatidylcholine at early times (15 s), and at later times (greater than or equal to 5 min) through the hydrolysis of primarily, if not exclusively, phosphatidylcholine (Pessin, M. S., and Raben, D. M. (1989) J. Biol. Chem. 264, 8729-8738). In contrast, IIC9 fibroblasts respond to the mitogenic treatments of (a) alpha-thrombin following chymotrypsin pretreatment or (b) epidermal growth factor by increasing their levels of diglycerides in a monophasic and sustained manner (Wright, T. M., Rangan, L. A., Shin, H. S., and Raben, D. M. (1988) J. Biol. Chem. 263, 9374-9380). In this report, we have analyzed the molecular species of the diglycerides generated by these two different treatments and have also examined the lipid response of IIC9 fibroblasts to platelet-derived growth factor. Based on both the molecular species analyses and the release of radiolabeled head-groups, all three of these different mitogenic treatments generate diglycerides primarily through the stimulation of phosphatidylcholine hydrolysis. However, while similar, the molecular species profiles of the diglycerides generated by these three treatments are not identical to the molecular species profile of total cellular phosphatidylcholine. In addition, the molecular species profiles of the diglycerides generated by these three mitogenic treatments greatly resemble each other, with significant differences between any two profiles occurring in at most one molecular species. This finding differs from that seen with alpha-thrombin stimulation alone, where the molecular species profile of the diglycerides generated following 5 min of alpha-thrombin stimulation is nearly identical to the molecular species profile of total cellular phosphatidylcholine. These data support the possibility of hormone-sensitive phosphatidylcholine pools or selective diglyceride metabolism.

Animals↗
PubMed1990

Kinetic and molecular species analyses of mitogen-induced increases in diglycerides: evidence for stimulated hydrolysis of phosphoinositides and phosphatidylcholine.

A wide variety of agonist-induced events appear to be mediated through an increase in cellular diglyceride levels. With regard to the ability of diglycerides to mediate these events, three important parameters must be considered: a) the kinetics of diglyceride generation, b) the absolute mass levels, and c) their molecular species. While this increase is often due to a stimulated hydrolysis of phosphoinositides, there is increasing evidence that the stimulated hydrolysis of phosphatidylcholine also contributes to agonist-induced increases in diglyceride levels. The kinetics of mass increases in diglyceride levels stimulated in cultured fibroblasts are agonist-dependent. High concentrations of alpha-thrombin stimulate a biphasic increase in diglyceride levels with the first phase peaking at 15 s and the second phase peaking at 5 min. In contrast, stimulation with epidermal growth factor, or platelet-derived growth factor, results in a monophasic increase in cellular diglyceride levels. Furthermore, the molecular species and phospholipid source of the stimulated diglycerides are also agonist-dependent. While the hydrolysis of phosphoinositides is major source of diglycerides initially generated in response to some agonists (15 s with alpha-thrombin at 500 ng/ml), phosphatidylcholine is hydrolyzed as well. Following longer incubations, or at all times following stimulation by epidermal growth factor or platelet-derived growth factor, phosphatidylcholine hydrolysis is the principal source of the stimulated diglycerides.

Cells, Cultured↗
PubMed1990

Chinese-white differences in the distribution of occlusive cerebrovascular disease.

The distribution of cerebrovascular lesions is affected by race. Blacks and Japanese have more intracranial occlusive cerebrovascular disease, while whites have more extracranial disease. Despite a high incidence of stroke in China, there are few formal studies of the distribution of vascular occlusive disease in Chinese populations. We compared clinical and angiographic features of 24 white and 24 Chinese patients with symptomatic occlusive cerebrovascular disease. In symptomatic vascular territories, whites had more severe (greater than or equal to 50% stenosis) extracranial lesions, while Chinese had more severe intracranial lesions. When we counted mild and severe lesions in a symptomatic territory, whites had more extracranial lesions while Chinese had more intracranial lesions. When we combined symptomatic and asymptomatic territories, whites had more extracranial lesions, while Chinese had more intracranial lesions. White patients reported more transient ischemic attacks. The distribution of lesions, however, was not explained by differences in incidence of transient ischemia, hypertension, diabetes, hypercholesterolemia, or ischemic heart disease between the groups. The preponderance of intracranial vascular lesions in Chinese patients is similar to that seen in blacks and Japanese. Racial differences in the occurrence of extracranial and intracranial lesions raise the possibility of a different underlying pathophysiology for the 2 locations.

Aged↗
PubMed1990

Prognostic significance of ventricular blood in supratentorial hemorrhage: a volumetric study.

We reviewed CTs from 47 patients with 48 spontaneous, supratentorial brain hemorrhages to determine the effect of ventricular blood on outcome. We correlated volumetric analysis of the parenchymal (P) and ventricular (V) blood, as well as other clinical and CT features, with clinical outcome in a statistical analysis. Hemorrhages were located in putamen 20/48 (42%), thalamus 13/48 (27%), lobar 9/48 (19%), caudate 3/48 (6%), and miscellaneous locations 3/48 (6%). Outcome in putaminal hemorrhages was highly correlated with the total (P + V) and P blood volumes, whereas the V blood was less important. For thalamic hemorrhages, outcome correlated more highly with the V and P + V volumes than with the P portion. Outcome for all hemorrhages was significantly correlated, in descending order of importance, with the severity of the initial neurologic deficit, P + V blood, hydrocephalus, the number of ventricles containing blood, P, V, and blood in the 4th ventricle. In general patients with more than 20 cc of V blood did poorly. Although hydrocephalus was associated with poor outcome, ventricular drainage did not benefit 8 of 9 patients.

Aged↗
PubMed1979

Mechanisms of acute carotid stroke.

In a three-year study, the clinical course and results of intracranial angiography were compared in patients having an acute stroke in the carotid artery territory combined with angiographic abnormalities indicating severe extracranial carotid stenosis or occlusion. Two major mechanisms of stroke were delineated. In one group, the angiographic intracranial abnormalities strongly suggested the presence of embolism in the cerebral vessels supplied by the stenotic or occluded carotid artery; many of these patients had no obvious transient ischemic attacks prior to their stroke and experienced a moderate to severe clinical deficit. In the other group, evidence of embolism was absent; many showed a widespread delay in cerebral arterial perfusion, experienced a greater frequency of transient ischemic attacks before their stroke, and had a milder stroke than did those with embolism.

Carotid Artery Diseases↗
PubMed1979

Reduced incidence of cerebral ischemia following rupture of intracranial aneurysms.

A randomized study was carried out to determine if the administration of reserpine and kanamycin to lower the concentration of vasoactive biogenic monoamines would reduce the incidence of cerebral vascular ischemic complications and death following the rupture of intracranial aneurysms. Twenty-six treated and twenty-eight control (untreated) patients were studied. In the preoperative period, eight control (untreated) patients developed symptomatic cerebral ischemia as opposed to one treated patient. There was no correlation between the preoperative clinical findings of ischemia and angiographic evidence of vasospasm. In the post-operative period four control and one treated patient developed symptomatic cerebral ischemia; vasospasm, as demonstrated by cerebral angiography, paralleled these findings.

Cerebral Infarction↗