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Biomedical subjects

M S Pessin

Publications and source records attributed to M S Pessin.

At least 37 records · Page 2Linked to original sources
PubMed1994

Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma.

Representational difference analysis was used to isolate unique sequences present in more than 90 percent of Kaposi's sarcoma (KS) tissues obtained from patients with acquired immunodeficiency syndrome (AIDS). These sequences were not present in tissue DNA from non-AIDS patients, but were present in 15 percent of non-KS tissue DNA samples from AIDS patients. The sequences are homologous to, but distinct from, capsid and tegument protein genes of the Gammaherpesvirinae, herpesvirus saimiri and Epstein-Barr virus. These KS-associated herpesvirus-like (KSHV) sequences appear to define a new human herpesvirus.

Acquired Immunodeficiency Syndrome↗
PubMed1994

The fatty acids in unremodelled trypanosome glycosyl-phosphatidylinositols.

Glycolipid A, the precursor of the glycosyl-phosphatidylinositol (GPI) anchor of the trypanosome variant surface glycoprotein, is constructed in two phases. First, the glycan is assembled on phosphatidylinositol (PI), yielding a glycolipid termed A'. Second, glycolipid A' undergoes fatty acid remodelling, by deacylation and reacylation, to become the dimyristoyl species glycolipid A. In this paper, we examine the fatty acid content of glycolipid A' and its cellular progenitors. A' contains exclusively stearate at the sn-1 position and a complex mixture of fatty acids (including 18:0, 18:1, 18:2, 20:4 and 22:6) at sn-2. Presumably these fatty acids derive from stearate-containing PI species which initially enter the biosynthetic pathway. We compared the diacylglycerol species from glycolipid A' with those from phosphatidylinositol to determine whether a subset of stearate-containing PIs is utilized for GPI biosynthesis. We found that the spectrum of stearate-containing diacylglycerols in PI is similar to that in A', although the proportions of each compound differ. Total PI in general was highly enriched in stearate-containing species. Differences in composition between glycosylated PI and total cellular PI may be due to the substrate specificity of the sugar transferase which initiates the GPI biosynthetic pathway. Alternatively, the species of PI present at the endoplasmic reticulum site of GPI biosynthesis may differ from those in total PI.

Animals↗
PubMed1994

Serial assessment of acute stroke using the NIH Stroke Scale.

BACKGROUND AND PURPOSE: The National Institutes of Health (NIH) Stroke Scale has been used in clinical trials to assess neurological outcome after investigational therapy for acute stroke. We used the NIH Stroke Scale to study the degree and time course of recovery in patients with acute stroke who were treated with conventional therapy. METHODS: We serially assessed 50 patients with ischemic stroke who presented within 24 hours of onset of symptoms. Patients were grouped by stroke subtype. Major neurological improvement was defined as a decrease in the stroke score by 4 points or more. RESULTS: The mean NIH stroke score for all patients improved significantly by 7 to 10 days and at last follow-up (average, 44 days). Major neurological improvement was seen in 5 of 41 patients (12%; 95% confidence interval [CI], 2% to 22%) by 24 hours, 11 of 40 patients (28%; 95% CI, 14% to 41%) by 48 hours, and 19 of 37 patients (51%; 95% CI, 35% to 67%) by follow-up. The subgroup of patients with middle cerebral artery territory embolism showed a similar pattern of improvement; in contrast, patients with lacunar infarcts did not show significant change in scores during the study period. The score on admission did not correlate with the degree of subsequent improvement or deterioration. CONCLUSIONS: A significant percentage of patients with acute ischemic stroke treated with conventional therapy show early improvement as assessed by the NIH Stroke Scale. The degree and time course of recovery may be influenced by stroke type.

Acute Disease↗
PubMed1993

Trypanosome metabolism of myristate, the fatty acid required for the variant surface glycoprotein membrane anchor.

The trypanosome variant surface glycoprotein (VSG) is anchored to the outer leaflet of the parasite plasma membrane by a glycosyl phosphatidylinositol (GPI). The VSG anchor is unique among GPIs in containing exclusively dimyristoylglycerol as its lipid moiety. Myristate is incorporated into the anchor precursor by sequential deacylation and specific reacylation with myristate. Although myristate is required for the VSG anchor, trypanosomes cannot synthesize this fatty acid and must import their entire supply from the host bloodstream, where it exists in low abundance. Chemical analysis of these parasites reveals that most of their myristate is in VSG protein, with no major lipid storage form. Unexpectedly, when these cells are radiolabeled with [3H]myristate in culture, most of the label is incorporated into phospholipids, with little into VSG. This apparent contradiction is explained by the fact that trypanosomes in culture medium elongate much of the [3H]myristate into palmitate and stearate, probably because the medium (with only 5% serum) contains limiting amounts of these fatty acids. In contrast, trypanosomes radiolabeled in whole blood (with higher concentrations of palmitate and stearate) do not modify most of the [3H]myristate, and instead utilize the major portion of it for GPI synthesis. Our studies suggest that bloodstream trypanosomes have evolved highly efficient means of directing myristate into the GPI biosynthetic pathway.

Acetates↗
PubMed1993

Anterior inferior cerebellar artery territory infarcts. Mechanisms and clinical features.

Arterial lesions, mechanisms, territory, and clinical features of anterior inferior cerebellar artery (AICA) territory infarcts are only based on necropsy cases. To our knowledge, no large clinical series has been reported. We selected nine consecutive patients with AICA territory infarction confirmed by magnetic resonance imaging and angiography. Atherosclerosis was the only cause and all patients were hypertensive. Patients with pure AICA territory infarcts (n = 4) were diabetic and likely had basilar branch occlusion due to basilar artery plaques that extended into the AICA or microatheroma that blocked the AICA origin. These patients had no or had only recently had (1 day) prodromata. Patients with AICA plus infarct (n = 5) had basilar artery occlusion at the AICA and reconstitution of the distal basilar artery by collaterals through hemispheric anastomoses from the posterior inferior cerebellar arteries and posterior communicating arteries. All these patients except one had prodromata. In seven of nine patients, cranial nerve involvement indicated a lateral pontine lesion in the territory supplied by the AICA. Only two patients had the complete AICA syndrome, and none of the patients had isolated vertigo. The outcome was good in seven of nine patients. Isolated unilateral AICA infarcts should be regarded as most likely due to small artery atherosclerotic disease in diabetic patients. More widespread infarctions that include that AICA territory are due to basilar artery occlusive disease.

Aged↗
PubMed1993

Very small (border zone) cerebellar infarcts. Distribution, causes, mechanisms and clinical features.

Computerized tomography (CT) and magnetic resonance imaging (MRI) allow accurate anatomical localization of large thromboembolic cerebellar infarcts in the territories of the cerebellar arteries and their branches. In addition, MRI and CT show very small cerebellar infarcts as discrete foci of signal change that are not easily localizable within well-defined arterial territories. They could be border zone infarcts. Their anatomy, mechanism and clinical features have not been studied. By reviewing our CT and MRI files over a 2-year period, we found 47 patients with very small cerebellar infarcts; 23 patients had angiography. Infarcts were cortical (32 patients), deep (10 patients) and both (five patients). Most lesions corresponded to border zone cerebellar infarcts. The mechanisms of infarction were (i) global hypoperfusion due to cardiac arrest (two patients); (ii) small or end (pial) artery disease due to intracranial atheroma or hypercoagulable states (nine patients); (iii) focal cerebellar hypoperfusion due to large artery (vertebral or basilar) occlusive disease (16 patients) or brain embolism (11 patients) resulting in infarcts in the watershed areas (27 patients total); (iv) unknown mechanism (nine patients, 19%). Large artery occlusive disease was more frequently observed in deep than in cortical infarcts (9 out of 15 versus 11 out of 37; P < 0.0001). The most frequent symptoms were dizziness, lightheadedness, unsteadiness with axial lateropulsion, dysarthria and limb clumsiness. These symptoms were either transient or recurrent, at times related to positional changes of the head or trunk. Position-related symptoms often persisted for weeks or months after the ischaemic event, and occurred mainly in patients with combined carotid and vertebrobasilar occlusive disease. Physical findings were either absent or included wide-based gait, lateropulsion, mild ipsilateral dysmetria, dysarthria or dysdiadochokinesia. We conclude that very small cerebellar infarcts are often found on CT and MRI. Their border zone distribution and frequent posturally related symptoms most often result from large or pial artery disease rather than from systemic hypotension.

Adult↗
PubMed1993

Postoperative brainstem and cerebellar infarcts.

OBJECTIVE: To study the clinical features and causes of postoperative brainstem and cerebellar infarcts. METHODS: Two groups were studied. The 10 group 1 patients had cardiac (eight) or aortic (two) surgery. The 12 group 2 patients had noncardiac-nonvascular surgery, including orthopedic (five), gynecologic (four), and general (three). Patients were studied by stroke services at university hospitals in Boston (13), Charlottesville (three), Baltimore (three), and Mainz (three) during 2 consecutive years. RESULTS: Onset of strokes was immediately postoperative (six), during the first 48 postoperative hours (nine), and delayed 3 days or more (seven). Clinical syndromes were altered level of consciousness or cognition (15), vestibulocerebellar (four), and hemiparesis with focal brainstem signs (three). Infarction involved the brainstem (13), cerebellum (13), and posterior cerebral artery hemispheric territory (10). Causes: In group 1, five infarcts were due to cardiogenic embolism and three to embolism from the aorta. One patient had a postoperative pontine lacunar infarct and one developed an infarct in the territory of a known stenotic basilar artery. In group 2, one patient had vertebral artery injury from instrumentation, one had medical complications with severe hemorrhage and hypotension, and 10 most likely had position-related vertebral artery thromboses. CONCLUSIONS: Patients with postoperative brainstem and cerebellar infarcts present with altered consciousness or vestibulocerebellar syndromes. The major cause of brain infarcts after cardiac surgery is embolism from the heart and aorta. The causes of infarction after general surgery are less clear, but neck positioning during or after surgery may play an important role by promoting thrombi in compressed arteries that later embolize intracranially when neck motion becomes free.

Adolescent↗
PubMed1993

Safety of anticoagulation after hemorrhagic infarction.

Cerebral hemorrhagic infarction visualized on CT, secondary to embolic stroke in an anticoagulated individual, is usually associated with clinically stable or improving neurologic signs; fear of transforming the hemorrhagic infarction into a hematoma, however, usually prompts cessation of anticoagulation until the blood has cleared on CT, despite the recognized risk of recurrent embolism during this non-anticoagulated period. We now report our experience with 12 patients with hemorrhagic infarction who remained anticoagulated. Eleven men and one woman, ages 33 to 77, developed hemorrhagic infarction while on heparin, warfarin, or both, for prevention of recurrent embolism. Patients were either continued on uninterrupted anticoagulation from stroke onset (n = 6), or anticoagulation was withheld for several days and then resumed (n = 4), or it was withheld for 5 and 14 days (n = 2) after stroke onset and then continued uninterrupted despite the CT appearance of hemorrhagic infarction. Eleven patients had a definite cardioembolic source for stroke (atrial fibrillation, seven; ventricular thrombus, two; and ventricular dyskinesia, two). One patient had carotid occlusion with local intra-arterial embolism. Hemorrhagic infarcts varied in size and were located in the middle cerebral artery territory in 11 patients and posterior cerebral artery territory in one. All patients remained clinically stable or improved on anticoagulation. Serial CTs showed fading hemorrhagic areas. When the risk of recurrent embolism is high, anticoagulation may be safely used in some patients with hemorrhagic infarction.

Adult↗
PubMed1993

Thrombolytic intervention in acute thrombotic and embolic stroke.

Stroke is one of the leading causes of death in the industrial nations of the world. Up to now, there has been no therapeutic strategy available which has been proven by controlled clinical trials. In the majority of acute stroke patients acute thrombosis contributes to carotid and vertebrobasilar arterial occlusions. Therefore, significant interest has focused on the possible value of fibrinolytic therapy in acute stroke. The principal goal is the rapid lysis of occluding thrombus with a minimum risk of intracranial or systemic hemorrhage. Clinical investigations on thrombolysis in cerebrovascular ischemia included different plasminogen-activators such as urokinase, streptokinase, and tissue plasminogen activator, either given systemically or locally via an intraarterial catheter. The pivotal trials conducted so far have revealed a wide range of recanalization rates, an acceptable safety and, also, encouraging effects on neurologic outcome. Thrombolysis itself carries the risk of intracranial bleeding, a practical limitation of this approach in acute stroke. On the other hand, hemorrhagic infarction and parenchymatous hematoma are natural consequences of thromboembolic stroke, possibly as a result of persistent occlusion of an artery. Hemorrhage following thrombolysis seems to show the same features seen in untreated patients and with an incidence similar to that in untreated patients. Future developments in thrombolysis in acute stroke should include improved early recruitment of patients, evaluation of noninvasive techniques in the pretreatment assessment of patients, the evaluation of advanced invasive techniques for delivery of the thrombolytic agent and assessment of combined treatment strategies. Clinical studies evaluating these strategies are currently under way.

Cerebral Hemorrhage↗
PubMed1993

Common carotid artery occlusion with patent internal and external carotid arteries: diagnosis and surgical management.

PURPOSE: Occlusion of the common carotid artery (CCA) is generally associated with occlusion of the ipsilateral internal carotid artery (ICA) and external carotid artery (ECA). Occasionally, however, collateral circulation to the ECA may preserve patency of the ICA via retrograde perfusion through the bulb. These patients may suffer ongoing transient ischemic attacks and risk for stroke. Recognition of this pathologic variant may allow for effective surgical intervention. METHODS: We have performed seven operations in six patients with occluded CCAs and patent ECA and ICAs. The occluded CCA was on the left side in each case (p < 0.01). Six of the operations were performed for ischemic symptoms, including amaurosis fugax in five patients, hemispheric TIA in one patient, and profound global ischemia in two patients who had concomitant occlusions of other extracranial vessels. In the five most recent cases the patent ECA and ICA above the occluded CCA were recognized by preoperative duplex scanning, which prompted cerebral angiography. A variety of reconstructive procedures were used, depending on the pathologic anatomy. These procedures included subclavian or axillary artery to carotid artery bypass with carotid endarterectomy (five), carotid endarterectomy with thrombectomy of the proximal CCA (one), and ascending aorta to carotid artery bypass (one). RESULTS: There were no strokes associated with the surgery, although one patient had transient neurologic symptoms and a seizure associated with documented reperfusion edema. Three of the patients had preoperative and postoperative transcranial Doppler studies that documented significant improvement in intracranial hemodynamics. Five of the patients have had continuously patent grafts with relief of symptoms for an average of 40 months (range 3 to 155 months). The remaining patient had graft occlusion after 72 months and underwent repeat operation for amaurosis fugax and global ischemia. His second graft remains patent, and he is symptom free 21 months later. CONCLUSIONS: Recognition of patent distal vessels above a CCA occlusion depends on a high index of suspicion, careful investigation of the carotid bulb with duplex scanning, and delayed arteriographic views of the bulb allowing for late collateral vessel filling. The favorable results in this small series of patients supports an aggressive surgical approach when patients with symptoms are encountered with patent distal vessels above an occluded CCA.

Aged↗
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↗