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Biomedical subjects

M Fisher

Publications and source records attributed to M Fisher.

At least 217 records · Page 12Linked to original sources
PubMed1997

Synergistic effects of citicoline and MK-801 in temporary experimental focal ischemia in rats.

BACKGROUND AND PURPOSE: Citicoline, a naturally occurring precursor of phosphatidylcholine, is neuroprotective and is currently being assessed in clinical trials. To evaluate potential synergistic neuroprotective effects of prolonged citicoline treatment and early N-methyl-D-aspartate (NMDA) antagonist therapy, suboptimal treatment regimens of citicoline and MK-801 were tested alone and in combination in a rat model of temporary focal ischemia. METHODS: Four groups of Sprague-Dawley rats (n = 12 per group) underwent 90 minutes of temporary middle cerebral artery occlusion (MCAO) with the suture model. Animals were randomly and blindly assigned to one of four treatment groups: (1) saline, vehicle; (2) MK-801, 0.5 mg/kg IV bolus at 60 minutes after MCAO followed by saline 1 mL/kg IP daily for 7 days; (3) saline IV at 60 minutes after MCAO followed by citicoline 250 mg/kg IP daily for 7 days; or (4) both MK-801 and citicoline (daily for 7 days) active treatment. Triphenyltetrazolium chloride staining was used to assess postmortem infarct volume. Neurological scores were determined daily. RESULTS: Premature mortality between days 2 and 4 was 33.3% in group 1, 41.7% in groups 2 and 3, and 25.0% in group 4. Mean corrected infarct volume was significantly reduced in group 4 compared with the others (175.2 +/- 89.3 mm3 in group 1, 179.1 +/- 78.5 mm3 in group 2, 163.9 +/- 73.7 mm3 in group 3, and 84.7 +/- 56.8 mm3 in group 4 [P < .02, ANOVA and P < .05, Scheffé's test for group 1 versus group 4]). Mean infarct volume in animals dying prematurely was significantly (P < .05, Student's t test) larger in group 1 than those surviving for 7 days (247.2 +/- 89.5 versus 139.2 +/- 68.2 mm3), but there was no significant difference in infarct volume in groups 2, 3, and 4 between animals dying prematurely and those surviving for 7 days. CONCLUSIONS: These results demonstrate synergistic neuroprotective effects of citicoline and an NMDA antagonist in temporary experimental focal ischemia.

Animals↗
PubMed1997

Glycine site antagonist attenuates infarct size in experimental focal ischemia. Postmortem and diffusion mapping studies.

BACKGROUND AND PURPOSE: The glycine site on the N-methyl-D-aspartate (NMDA) receptor complex offers a therapeutic target for acute focal ischemia, potentially devoid of most side effects associated with competitive and noncompetitive NMDA antagonists. METHODS: A novel glycine receptor antagonist, ZD9379, was studied in 70 Sprague-Dawley rats using the suture occlusion model of permanent middle cerebral artery occlusion (MCAO). In the first experiment, 20 rats received an initial bolus of vehicle or 10 mg/kg ZD9379 (n = 10 in each group) 30 minutes after MCAO, followed by a continuous infusion of the same dose per hour for 4 hours. Diffusion-weighted MRI with echo-planar acquisition was used to generate maps of the apparent diffusion coefficient (ADC) of water. In a second experiment, 50 rats were assigned to five groups: vehicle and 10, 5, 2.5, and 1 mg/kg ZD9379 (n = 10 in each group) with the same dosing protocol but no imaging. In both experiments, infarct volume was determined by 2,3,5-triphenyltetrazolium chloride staining. RESULTS: In the first experiment, before therapy was begun, there was no significant difference in ADC-derived ischemic lesion volume between the two groups. Over time, the 10-mg/kg ZD9379-treated rats had a significant delayed regional recovery of reduced ADC values in the peripheral parietal cortex (P = .0156). Postmortem corrected infarct volume at 24 hours after MCAO was significantly smaller in the group treated with 10 mg/kg ZD9379 than in the vehicle group (119.2 +/- 52.2 versus 211.2 +/- 50.0 mm3 [mean +/- SD]; P = .0008; a reduction of 43.6%). In the second experiment, postmortem corrected infarct volumes in rats receiving 10, 5, and 2.5 mg/kg ZD9379 were significantly smaller than in those receiving vehicle, a reduction of 42.6%, 51.4%, and 42.9%, respectively (P = .0001). CONCLUSIONS: This study demonstrates that 2.5- to 10-mg/kg doses of ZD9379 initiated 30 minutes after MCAO significantly reduced infarct size. Diffusion mapping disclosed a delayed treatment effect of this glycine antagonist in focal ischemia, confirmed by the postmortem study.

Animals↗
PubMed1997

Anterior circulation ischemia.

Ischemic stroke in the anterior or carotid artery territory is the most common type of stroke, with a wide range of clinical manifestations. Specific stroke syndromes reflect the vascular territories involved and range from small, lacunar infarcts to those that involve the entire middle cerebral artery territory. Diagnostic imaging with computed tomography or magnetic resonance imaging is very useful for confirming the location and extent of anterior circulation strokes. Important advances for the acute management of these patients have occurred recently and more should be forthcoming soon.

Animals↗
PubMed1996

Randomized trial of recombinant platelet factor 4 versus protamine for the reversal of heparin anticoagulation in humans.

BACKGROUND: Protamine reverses heparin anticoagulation, but it can have important side effects. We compared the safety and effectiveness of intravenous recombinant platelet factor 4 (rPF4) as an alternative to protamine in a randomized blinded trial. METHODS AND RESULTS: In 81 patients having diagnostic cardiac catheterization, baseline hemodynamics were measured after a 5000-U bolus of heparin. Repeat measurements were obtained at the end of the procedure, and the anticoagulation status was determined by an activated coagulation time (ACT) and activated partial thromboplastin time (aPTT). Patients then received either protamine (50 mg IV over 10 minutes) or rPF4 (1.0 mg/kg IV over 2 minutes) in a blinded fashion. Serial measurements of hemodynamic and clotting functions were performed 5, 10, 20, and 30 minutes after drug administration. Follow-up measurements and clinical assessments were made at 1, 4, 6, and 24 hours later and after 7 days. Before drug administration, ACTs, aPTTs, and hemodynamics were similar among the groups. After drug infusion, there was no difference in ACT between the protamine and rPF4 patients. At 20 and 30 minutes after drug infusion, ACT and aPTT were slightly higher in those receiving rPF4, but these changes were small and of no clinical significance. There were no clinically meaningful differences in any of the hemodynamic variables between the groups, and there were no serious side effects in any patient. CONCLUSIONS: At the dose used in this study, rPF4 was well tolerated and reversed the anticoagulant effect of heparin. These data support its continued evaluation as an alternative to protamine after cardiac surgery.

Adult↗
PubMed1996

Hematologic disorders associated with ischemic stroke.

Hematological disorders underlie a small proportion of all ischemic strokes. The association of these coagulation abnormalities with ischemic stroke is not always clear. The etiology of stroke still remains uncertain in a large number of cases and proper screening for coagulation abnormalities and the discovery of new coagulation disorders will probably increase the rate of strokes attributable to these causes. Since large case-control studies with unselected and consecutive stroke patients from different ethnic origins have not yet been performed to determine the role of coagulation abnormalities in ischemic stroke, our knowledge is dependent on case reports and small series of mostly younger patients. Extensive hematologic evaluation of unselected stroke patients will likely yield little useful information and be too expensive. Every stroke patients needs a careful evaluation, and in selected cases, this should include coagulation parameters. Patients with unexplained strokes after a careful evaluation, previous thrombotic episodes, or a positive family history for thrombosis, are good candidates for further coagulation studies. As long as the hypercoagulable state persists, both arterial and venous thromboembolic recurrences can be expected. Many of these patients may benefit from anticoagulants. In patients with hereditary coagulation disorders, studies should be extended to close relatives. Since some coagulation tests are fairly expensive, provide only equivocal data, and are not widely available, we advise a step-by-step approach starting with the patient and family history.

Anemia, Sickle Cell↗
PubMed1996

A salt-resistant plasma membrane carbonic anhydrase is induced by salt in Dunaliella salina.

The mechanisms allowing proliferation of the unicellular green alga Dunaliella salina in up to saturating NaCl concentrations are only partially understood at present. Previously, the level of a plasma membrane Mr 60,000 protein, p60, was found to increase with rising external salinities. Based on cDNA cloning and enzymatic assays, it is now shown that p60 is an internally duplicated carbonic anhydrase, with each repeat homologous to animal and Chlamydomonas reinhardtii carbonic anhydrases, but exceptional in the excess of acidic over basic residues. Increasing salinities, alkaline shift, or removal of bicarbonate induced in D. salina parallel increases in the levels of p60, its mRNA, and external carbonic anhydrase activity. Moreover, purified p60 exhibited carbonic anhydrase activity comparable to other carbonic anhydrases. A p60-enriched soluble preparation showed maximal carbonic anhydrase activity at approximately 1.0 M NaCl and retained considerable activity at higher salt concentrations. In contrast, a similar preparation from C. reinhardtii was approximately 90% inhibited in 0.6 M NaCl. These results identified p60 as a structurally novel carbonic anhydrase transcriptionally regulated by CO2 availability and exhibiting halophilic-like characteristics. This enzyme is potentially suited to optimize CO2 uptake by cells growing in hypersaline media.

Alkalies↗
PubMed1996

Is alignment within 8 prism diopters of orthotropia a successful outcome for infantile esotropia surgery?

OBJECTIVE: To determine if there is better long-term motor alignment or sensory outcome 5 years after surgery for infantile esotropia for patients who exhibit any of three categories of alignment 6 months after surgery: orthotropia, up to 8 prism diopters (delta) of esotropia, or up to 8 delta of exotropia. DESIGN: A 15-year prospective study with 5-year outcome determination was conducted in surgically treated esotropic infants. RESULTS: Of 118 patients in the study group, 24 had orthotropia, 84 had up to 8 delta of esotropia, and 10 had up to 8 delta of exotropia 6 months after surgery. The patients who were orthotropic 6 months after surgery were more likely to show good alignment and better binocularity 5 years after surgery than were patients with small-angle esotropia or small-angle exotropia. Patients who were esotropic 6 months after surgery were more likely to have good alignment and binocularity 5 years after surgery than were patients who were exotropic 6 months after surgery. CONCLUSION: Small-angle esotropia, small-angle exotropia, and orthotropia are not equally desirable outcomes after surgery for infantile esotropia. Orthotropia is a decidedly better outcome than a small-angle esotropia, which is preferable to a small-angle exotropia.

Esotropia↗
PubMed1996

The role of spreading depression in focal ischemia evaluated by diffusion mapping.

This study investigated the role of spontaneous and induced spreading depression (SD) on the evolution of focal ischemia in vivo. We induced focal ischemia in 12 rats using the middle cerebral artery suture occlusion (MCAO) method. Chemical stimulation of nonischemic ipsilateral cortex by potassium chloride application (KCl group; n = 7) and saline (NaCl group; n = 5) was performed at 15, 30, 45, and 60 minutes following MCAO, and SD was detected electrophysiologically. Ischemic lesion volumes assessed over 15-minute intervals, evaluated by continuous apparent diffusion coefficient (ADC) of water mapping, demonstrated that the ischemic region increased significantly during 15-minute time epochs with a single SD episode (36.5 +/- 12.9 mm3, mean +/- SD) or multiple SD episodes (39.8 +/- 22.3) compared with those without SD (13.9 +/- 11.5) (p = 0.0009). Infarct volume at postmortem 24 hours after MCAO was significantly larger in the KCl group, with more total SDs (237.8 +/- 13.8) than the NaCl group (190.5 +/- 12.6) (p = 0.0001). This study demonstrates that ischemia-related and induced SDs increase significantly ischemic lesion volume in vivo, supporting the hypothesis for a causative role of SD in extending focal ischemic injury.

Animals↗
PubMed1996

The effects of prolonged treatment with citicoline in temporary experimental focal ischemia.

Potential therapeutic effects of cytidine 5-diphosphocholine (citicoline), a key intermediary in the biosynthesis of the membrane phospholipid, phosphatidylcholine, are presumably related to enhanced phospholipid synthesis in the ischemic brain. We evaluated prolonged citicoline treatment in a temporary focal ischemia model. Using the suture occlusion model, we induced 2 hours of temporary ischemia in 30 Sprague-Dawley rats. The rats were randomly and blindly assigned to receive intraperitoneally 500 mg/kg citicoline (HD), 100 mg/kg citicoline (LD) or physiologic saline as the control group once daily for 7 days (n = 10 per group) beginning at the time of reperfusion. Neurological scoring (0-5 scale) was performed daily. After elective sacrifice on day 7, or earlier if death occurred prematurely, the brains underwent 2,3,5-triphenyltetrazolium chloride (TTC) staining for calculation of corrected infarct and edema volume. The mean corrected infarct volume in the HD group was 125 +/- 45.2 mm3 (mean +/- SD), significantly smaller than controls, 243.5 +/- 88.6 mm3 (p < 0.01, Scheffe's-test). The LD group infarct volume was 200.2 +/- 62.8 mm3 (N.S.). The mean amount of brain edema in the HD group was 46.4 +/- 45.6 mm3 was smaller than the controls, 92.3 +/- 54.4 mm3 and the LD group, 84.9 +/- 71.7 mm3 (N.S.). Mortality before day 7 in the HD was 30% while it was 50% in the two other groups. The neurologic score on day 7 was 2.5 +/- 1.8 in the HD group, 3.3 +/- 1.8 in the LD group and 3.4 +/- 1.7 in controls (N.S.). These results demonstrate that extended high dose citicoline treatment significantly reduced infarct volume in this temporary focal ischemia model and that there was a trend toward reducing brain edema and mortality. These effects may be related to membrane stabilization and inhibition of free fatty acid release.

Animals↗
PubMed1996

Violence and mental health problems among urban high school students.

PURPOSE: We sought to determine the extent of exposure to violence and its relationship to other mental health risks among an urban teenage population. METHODS: Students attending regularly scheduled physical education classes completed a Violence Survey, a Suicidal Ideation Survey, the Depression Self-Rating Scale (DSRS), and the Adolescent Alcohol Involvement Scale. Of the 630 students who completed the anonymous assessment 45% were male, 55% female, 61% black, 30% Hispanic; 54% grades 9-10, and 46% grades 11-12. RESULTS: Half of the students reported knowing someone who had been murdered, 61% indicated they had witnessed a robbery, 59% had witnessed a beating, 37% had witnessed a shooting, and 31% had witnessed a stabbing. Mental health problems reported by these students included: depression (DSRS score > 13) in 31%, suicidal ideation in 16%, suicide attempts in 10%, drinking > 1 x per month in 21%, and drinking daily in 5%. Univariate analysis revealed that students who witnessed a shooting or stabbing were more likely (p < .05) to be both male and black. Multivariate analysis revealed that students reporting knowing someone who was murdered were twice as likely to report suicidal ideation and four times as likely to report suicide attempts. Witnessing a stabbing was associated with twice the likelihood of reporting suicide ideation and three times the likelihood of reporting suicide attempts. Witnessing a shooting was associated with twice the likelihood of alcohol use. Witnessing a beating or robbery had no significant relationship to measured variables. CONCLUSIONS: Among this population of urban teenagers there are many who have witnessed violence and a subgroup who have witnessed shootings and stabbings and are at increased risk for mental health problems. A comprehensive medical and psychosocial history should include a violence assessment for all urban teens.

Adolescent↗
PubMed1996

Sports participation in an urban high school: academic and psychologic correlates.

PURPOSE: To study positive and negative correlates of sports participation in inner-city youth. METHODS: We distributed anonymous questionnaires to 838 students in gym classes of an urban New York City High School. Forty five percent of students were male and 55% female, with mean age 16.0 years; 64% in grades 9-10, and 36% in grades 11-12; 63% black, 27% Hispanic, and 10% other; and 30% A/B students, 38% C students, and 32% D/F students. RESULTS: All students reported some involvement in sports: 37% in 1-2 sports, 29% in 3-4 sports 24% in > or = 5 sports; 20% played on local teams, and 12% on junior or senior varsity. Approximately one-third each reported no weekday sports participation (30%), 1-2 hours per day (34%), or > or = 3 hours (36%); and 34% reported no participation on weekends, 26% reported 1-2 hours per day, and 40% > or = 3 hours. Basketball, volleyball, baseball, and weight lifting were the most common sports. Enjoyment, recreation, and competition were the most commonly reported reasons for participation. While 86% of subjects considered school "extremely" or "very" important, 35% considered sports "extremely" or "very" important. However, many believed they would "definitely" or "probably" receive an athletic scholarship (52% males, 20% females). Males reported more (p < .05) weekday, weekend, and team participation, and greater expectations (p <.001) of a future in sports. Sports involvement was not statistically associated with academic performance or scores on either the Rosenberg Self-Esteem Scale or Depression Self Rating Scale. Steroid use, at least once, was reported by 11% of males and 4% of females. Thirteen percent of students (21% males, 6% females) tried to gain weight for sports and 20% of both males and females tried to lose. Sports injuries within the past year were reported by 15% of students, and approximately three-quarters could correctly answer each of five questions about basic first aid. CONCLUSIONS: The data indicate that most of these urban youth had athletic involvement, many had unrealistic expectations for their futures, and some utilized unhealthy behaviors in an attempt to enhance performance. Among these students, no association was found between sports involvement and academic performance, self-esteem, or depression.

Adolescent↗
PubMed1996

AIDS knowledge, concerns, and behavioral changes among inner-city high school students.

Knowledge of AIDS, attitudes toward AIDS and condoms, and behavioral changes because of AIDS were studied in 771 students, Grades 9-12 (mean age, 16 years) who completed anonymous questionnaires in gym classes of a New York City high school. Students demonstrated good knowledge of AIDS, with some misconceptions, and significant concerns about AIDS, with some behavioral changes, but most continued to engage in high-risk behaviors. These data indicate that efforts aimed at HIV/AIDS prevention in adolescents must translate knowledge and concerns into behavioral change.

Acquired Immunodeficiency Syndrome↗