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Biomedical subjects

M Fisher

Publications and source records attributed to M Fisher.

At least 361 records · Page 20Linked to original sources
PubMed1991

Hemorheological factors in cerebral ischemia.

We investigated 100 consecutive cerebral ischemia patients for hemorheological alterations. We measured whole and adjusted blood viscosity at 75 and 1,500 sec-1, plasma viscosity, red blood cell aggregation by the zeta sedimentation ratio, and red blood cell deformability using the centrifugal deformability technique. Patients were studied within 72 hours of the acute ischemic event, and 66 were available for follow-up evaluation approximately 2 months later. Two age- and sex-matched control groups were evaluated: 20 nonvascular neurological inpatients (patient controls) and 45 normal volunteers (normal controls). Compared with normal controls, we found significant acute increases in whole blood viscosity (1,500 sec-1), plasma viscosity, fibrinogen concentration, and zeta sedimentation ratio; the latter two variables were also increased at follow-up. Fibrinogen concentration was significantly associated with zeta sedimentation ratio and plasma viscosity and was increased for patient controls. There was a trend toward normalization of acute abnormalities over the 2-month follow-up period, and patients with more severe strokes tended to have more extensive hemorheological abnormalities. Among patients with severe stroke, fibrinogen concentration was significantly associated with the platelet activation peptide beta-thromboglobulin acutely (r = 0.63, p less than 0.005). We conclude that hemorheological abnormalities in cerebral ischemia are largely nonspecific findings, with the likely exception of patients with severe stroke.

Adult↗
PubMed1991

A 21-aminosteroid inhibits stimulated monocyte hydrogen peroxide and chemiluminescence measurements from MS patients and controls.

Monocytes are recruited to active sites of multiple sclerosis (MS) demyelination and may promote local tissue injury by generating an inflammatory response, mediated in part by the production of toxic oxygen metabolites. Corticosteroids are frequently and effectively used to ameliorate MS exacerbations, despite inadequate knowledge about the mechanism. We assessed the effects of a 21-aminosteroid, U74500A, a new class of steroid derivatives without glucocorticoid or mineralocorticoid effects, on the production of hydrogen peroxide (H2O2) and chemiluminescence by stimulated monocytes harvested from 8 stable MS patients and age- and sex-matched controls. H2O2 measurements and chemiluminescence were significantly reduced in both groups by U74500A. These results demonstrate that 21-aminosteroids reduce production of toxic oxygen metabolites by monocytes and thus their inflammatory potential, suggesting that these agents may be potentially effective and safe treatment for MS exacerbations.

Adult↗
PubMed1991

Ischemic cerebral vascular disease: an overview.

The management of patients with cerebrovascular ischemic disease (ICD) is rapidly changing due to newer diagnostic approaches and therapies being developed. In the present article, the author reviews part of his experience in the clinical and basic fields of ICD which is the most common neurologic problem leading to acute hospitalization. Clinico-anatomic categories of ICD as well as prognosis and differential diagnosis are discussed. Data from basic and research are analyzed with a main focus on their implications for clinical management.

Brain Ischemia↗
PubMed1991

Primary intracerebral and subarachnoid hemorrhage. An approach to diagnosis and therapy.

The diagnosis of primary intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) has become easier with the advent of modern imaging techniques. The incidence of ICH has declined, while SAH has remained relatively constant. The prognosis for both disorders remains dismal and the mortality rate is substantially higher than that observed with ischemic stroke. Early imaging with CT or MRI is important for rapid and accurate diagnosis. General medical management in a skilled nursing facility should be available for patients who are not moribund. Therapy for ICH is predominantly supportive and effective medical and surgical intervention remains elusive. For SAH, calcium channel blockers may reduce cerebral ischemic complications related to vasospasm, but effective medical therapy to prevent rebleeding has not been established. Early surgery after SAH should be considered in clinically stable patients. Many challenges remain regarding the prevention and treatment of both these cerebral hemorrhage subtypes.

Cerebral Hemorrhage↗
PubMed1991

Metabolic responses to ammonium acetate infusion in exercising horses.

The relationship between elevated plasma ammonia (NH3) levels, fatigue development and muscle metabolism were examined in horses during a submaximal fatigue test. Eight Quarter Horse mares were intravenously infused prior to exercise with either sodium acetate (control) or ammonium acetate (AMINF), and exercised to fatigue on an 11% grade treadmill, carrying 27 kg of lead. Time to fatigue was not different (P greater than 0.05) between groups. Intramuscular NH3 and lactate increased (P less than 0.001) during exercise; however, the treatment did not (P greater than 0.05) affect either. A treatment by exercise interaction (P less than 0.01) occurred for plasma NH3. The reciprocal relationship between changes in plasma and intramuscular alanine (ala) and glutamate (glu) indicated activation of the glucose-alanine cycle. Plasma glutamine (gln) increased (P less than 0.001) during exercise; however intramuscular gln was not (P greater than 0.05) altered. The excretion of urea-N was depressed as a result of exercise while the orotic acid/creatinine ratio did not (P greater than 0.05) change. The amino acids and urinary metabolites were not (P greater than 0.05) affected by treatment. These results did not show any metabolic evidence for a role of increased plasma NH3 levels in fatigue development. However this study did provide insight into other aspects of nitrogen metabolism during exercise in the horse.

Acetates↗
PubMed1991

Atherosclerosis: cellular aspects and potential interventions.

The pathogenesis of atherosclerosis has been extensively studied and the cellular aspects increasingly characterized. This review will focus on the basic pathology, presumed cellular events, cellular interactions, cell-lipid relationships, and potential therapies of atherosclerosis. Fatty streaks, fibrous plaques, and complicated plaques are the pathologic hallmarks of atherosclerosis. These lesions insidiously progress, and symptoms appear to develop when the plaque luminal surface destabilizes. The major cellular contributors to plaque development are monocytes/macrophages, endothelial cells, smooth muscle cells, and, to a lesser degree, lymphocytes and platelets. They interact in a complicated fashion. Growth factors and cytokines produced by these cells are also of great importance for cell-cell interaction. Hemodynamic factors contribute to atherogenesis at preferential sites within the arterial vasculature, presumably by effects on the cellular mechanisms. Hyperlipidemia, especially elevations of total and LDL-cholesterol, has been well characterized as an atherosclerotic risk factor. Cellular modification of LDL-cholesterol, primarily by oxidation, leads to more rapid uptake by macrophage-derived foam cells, enhancing plaque growth by this and other mechanisms. These observations may unify the cellular and lipid contributors to atherogenesis. Therapies directed at the cellular contributors to atherosclerosis are being assessed. Dietary n-3 fatty acid supplementation reduces the extent of experimental atherosclerosis, and human studies are in progress. Many potential cellular effects of n-3 fatty acids have been demonstrated. Other potential therapies for atherosclerosis that probably work at the cellular level include calcium channel blockers, antioxidants, and heparinoids. An exciting new era of atherosclerosis research and, hopefully, therapy has dawned, as knowledge about its cellular basis accrues.

Animals↗
PubMed1991

Sensitive, colorimetric enzyme amplification cascade for determination of alkaline phosphatase and application of the method to an immunoassay of thyrotropin.

A highly sensitive flavin adenine dinucleotide-3'-phosphate (FADP)-based enzyme amplification cascade has been developed for determining alkaline phosphatase (ALP; EC 3.1.3.1). The cascade detects ALP via the dephosphorylation of the novel substrate FADP to produce the cofactor FAD, which binds stoichiometrically to inactive apo D-amino acid oxidase (D-AAO). The resulting active holo D-AAO oxidizes D-proline to produce hydrogen peroxide, which is quantified by the horseradish peroxidase-mediated conversion of 3,5-dichloro-2-hydroxybenzenesulfonic acid and 4-aminoantipyrine to a colored product. The FADP-based enzyme amplification cascade has been used in a novel releasable linker immunoassay (RELIA) to quantify thyrotropin (TSH). In the assay, TSH is first captured onto antibody-coated chromium dioxide particles. After formation of an antibody-TSH sandwich with a dethiobiotinylated second antibody, the complex is reacted with a streptavidin-ALP conjugate. Biotin is then used to release the conjugate into solution, and ALP is quantified in an automated version of the FADP-based amplification cascade on the aca discrete clinical analyzer (Du Pont). The sensitivity of the colorimetric RELIA assay for TSH (less than 0.1 milli-int. unit/L) is comparable with that of fluorometric assays. This technology provides a way to adapt to the aca high-sensitivity immunoassays for a wide range of analytes via colorimetric detection.

Clinical Enzyme Tests↗
PubMed1991

Acute rheumatic fever in West Virginia. Not just a disease of children.

Rheumatic fever is a poststreptococcal disease that is receiving renewed attention by the medical community. We describe a recent increase in the number of observed cases of acute rheumatic fever (ARF) in West Virginia. This is the fifth report of a recent increase in the incidence of ARF in the Ohio Valley area in the last 4 years. In contrast to the other reports, nearly two thirds of our cases of ARF were in adults, more than half of whom had suffered previous bouts of ARF. In these adults with recurrences, none was taking prophylactic penicillin at the time of presentation. Carditis was present in seven adults, two without a history of carditis. Arthritis was present in all adult patients. These data indicate a possible geographic phenomenon related to the increased number of observed cases of ARF and document that ARF is not simply a disease of childhood. Furthermore, our findings highlight the need for extended penicillin prophylaxis for secondary prevention of ARF, especially for those with an increased risk of acquiring a streptococcal upper respiratory tract infection.

Acute Disease↗
PubMed1991

In vitro interaction of astrocytes and pericytes with capillary-like structures of brain microvessel endothelium.

A new method to study the interaction of astrocytes and pericytes with cerebral capillary endothelial cells in vitro is described. Endothelial cells derived from bovine brain were cultured on gelatin coated slides and covered with type 1 collagen. Endothelial cells aggregated and formed capillary-like structures (CS) within 3 days. The lining cells of the CS stained immunohistochemically for factor VIII-related antigen. Astrocytes isolated from neonatal mice or pericytes from bovine brain were added to the preparations after the formation of CS. After various periods of co-culture, the slides were fixed with methanol and examined with the immunohistochemical stain for glial fibrillary acidic protein or smooth muscle actin to demonstrate astrocytes or pericytes respectively. Five hours after addition, only 10% of astrocytes were associated with CS. However, by 24 hours, 70% of the astrocytes had assumed a position adjacent to the CS. The astrocytes then developed processes which were intimately apposed to the CS by 3 days, at which time they resembled the in vivo structural relationship between astrocytes and microvessels that occur in areas of central nervous system injury. Progressive elongation of the astrocytes or their processes at the CS was evident at 6 and 9 days of co-culture. The cross-section of CS co-cultured with astrocytes showed continuous cells surrounding a lumen, and the endothelial cells appeared to be connected by tight junctions. When pericytes were added to CS cultures they also preferentially associated with CS, but the contact occurred more rapidly than with astrocytes, 50% being associated with CS by 5 hours. The CS were almost completely covered with elongated pericytes by 24 hours. A chemotactic assay was developed that showed that there was a chemotactic attraction of pericytes to the CS. Thus an in vitro system is now available to study the interrelationships of these cell types and their interaction in development, regeneration and differentiation of the blood-brain barrier.

Animals↗
PubMed1990

Inhibition of 3-hydroxy-3-methylglutaryl coenzyme A synthase by antibiotic 1233A and other beta-lactones.

3-Hydroxy-3-methylglutaryl CoA synthase was shown to be inhibited in a time-dependent, irreversible manner by compounds containing the substituted beta-lactone functionality found in the natural product 1233A. The rate of inactivation (kinact) was found to approach the rate of catalysis (kcat). The inactivation was irreversible over several hours. A related compound lacking the hydroxymethyl substituent on the beta-lactone ring is a reversible inhibitor and is competitive with respect to acetylCoA. The results are consistent with beta-lactone ring opening by the active site Cys to form an enzyme bound thioester.

Acetates↗
PubMed1990

Cyclosporin therapy for steroid resistant nephrotic focal glomerulosclerosis.

A young man with focal glomerulosclerosis and severe steroid resistant nephrotic syndrome was treated with oral cyclosporin for six months without histological evidence of drug induced nephrotoxicity. A marked and sustained partial remission of the degree of proteinuria one year following cessation of treatment was not accompanied by a deterioration in renal function. Cyclosporin may have a role, as yet not fully defined, in the treatment of steroid-resistant or dependent nephrotic syndrome.

Administration, Oral↗
PubMed1990

Intracranial hemorrhage after use of tissue plasminogen activator for coronary thrombolysis.

Tissue plasminogen activator (tPA), an approved coronary thrombolytic agent, can cause serious bleeding. We report the cases of six patients with intracranial hemorrhage after tPA treatment for acute myocardial infarction. None of the patients were hypertensive at admission, and only one was hypertensive during therapy. Intravenous tPA, 100 mg, was followed by continuous intravenous heparin infusion; intracranial hemorrhage occurred between 2 and 14 hours after tPA infusion ended and between 3 and 17 hours after heparin therapy was started. The partial thromboplastin time (PTT) was excessively prolonged (from 81 s to more than 150 s) in all patients at onset of intracranial hemorrhage. The intracerebral hematomas were predominantly of lobar location, and two patients had multiple simultaneous hemorrhages. Four patients died from massive intracranial hemorrhage; the mechanism for these hemorrhages was unclear. Factors possibly related to hemorrhage include a systemic fibrinolytic state or a platelet anti-aggregant effect produced by tPA and enhanced hemorrhagic tendency caused by the combined effects of tPA and heparin. Local vascular changes at the bleeding site remain as potential contributing factors for isolated intracranial hemorrhage.

Aged↗
PubMed1990

Altered coagulation in cerebral ischemia. Platelet, thrombin, and plasmin activity.

We investigated hemostatic function in patients with cerebral ischemia by evaluating platelet activation, fibrin generation, and fibrinolysis. Plasma beta-thromboglobulin, an index of platelet activation, was significantly increased both acutely (14.9 +/- 9.2 ng/mL; n = 85) and approximately 2 months later (17.3 +/- 10.1 ng/mL; n = 57). Thrombin activity was measured using assays for fibrinopeptide A and fibrin D-dimer. Increased fibrinopeptide A was found in 9 (11.5%) of 78 patients acutely and 6 (10.7%) of 56 at follow-up; fibrin D-dimer levels were significantly increased acutely (166 +/- 188 ng/mL; n = 66) but not at follow-up. Fibrinolytic activity was measured using assays for fibrinopeptide B-beta 1-42 and plasminogen activator inhibitor 1. Fibrinopeptide B-beta 1-42 was significantly reduced acutely (6.3 +/- 2.2 pmol/mL; n = 35) and at follow-up (4.8 +/- 1.5 pmol/mL; n = 21). Plasminogen activator inhibitor 1 was normal acutely (20.1 +/- 12.0 ng/mL; n = 73) but increased at follow-up (27.8 +/- 20.1 ng/mL; n = 45). These results demonstrate that patients with cerebral ischemia have abnormal hemostatic function that is not explained by the acute phase reaction, and that components of the prethrombotic state are present in some of these patients.

Adult↗