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Biomedical subjects

M Fisher

Publications and source records attributed to M Fisher.

At least 181 records · Page 10Linked to original sources
PubMed1998

A glycine site antagonist, ZD9379, reduces number of spreading depressions and infarct size in rats with permanent middle cerebral artery occlusion.

BACKGROUND AND PURPOSE: Spreading depressions (SDs) occur in experimental focal ischemia and contribute to lesion evolution. N-Methyl-D-aspartate (NMDA) antagonists inhibit SDs and reduce infarct size. The glycine site on the NMDA receptor complex offers a therapeutic target for acute focal ischemia, potentially devoid of many side effects associated with competitive and noncompetitive NMDA antagonists. We evaluated the effect of the glycine antagonist ZD9379 on SDs and brain infarction. METHODS: Male Sprague-Dawley rats (n = 18) weighing 290 to 340 g undergoing permanent middle cerebral artery occlusion (MCAO) were randomly and blindly assigned to receive drug or placebo: group 1 (pre-MCAO treatment group; n=5), a 5-mg/kg bolus of ZD9379 over 5 minutes followed by 5 mg/kg per hour drug infusion for 4 hours beginning 30 minutes before MCAO; group 2 (post-MCAO treatment group; n=7), a 5-mg/kg bolus of ZD9379 30 minutes after MCAO followed by 5 mg/kg per hour drug infusion for 4 hours; and group 3 (control group; n=6), vehicle for 5 hours beginning 30 minutes before MCAO. SDs were monitored electrophysiologically for 4.5 hours after MCAO by continuous recording of cortical DC potentials and electrocorticogram. Infarct volume was measured 24 hours after MCAO by 2,3,5-triphenyltetrazolium chloride staining. RESULTS: Corrected infarct volume was 90+/-72 mm3 (mean+/-standard deviation) in group 1, 105+/-46 mm3 in group 2, and 226+/-40 mm3 in group 3 (P<.001). The corresponding numbers of SDs in the three groups were 8.2+/-5.8, 8.1+/-2.5, and 16.0+/-5.1, respectively (P<.01). When all animals (n=18) were analyzed, infarct volumes and the number of SDs were significantly correlated (r=.68, P=.002). CONCLUSIONS: This study demonstrated that ZD9379 initiated before or after MCAO significantly reduced the number of SDs and infarct volume in a permanent focal ischemia model, implying that ZD9379 is neuroprotective and its neuroprotective effect may be related to inhibiting ischemia-related SDs.

Analysis of Variance↗
PubMed1998

A novel endothelin antagonist, A-127722, attenuates ischemic lesion size in rats with temporary middle cerebral artery occlusion: a diffusion and perfusion MRI study.

BACKGROUND AND PURPOSE: Endothelins (ETs) are potent vasoconstrictors. Plasma ET levels increase during acute brain ischemia and may worsen the ischemic damage. Diffusion-weighted MRI (DWI) and perfusion imaging (PI) are powerful tools for evaluation of acute cerebral ischemia. We studied the effects of A-127722, a novel ET(A)-selective ET antagonist, on cerebral ischemic lesion size using 2,3,5-triphenyltetrazolium chloride (TTC) staining postmortem, on acute ischemic lesion development with DWI, and on the cerebral circulation using PI. METHODS: Twenty male Sprague-Dawley rats received either 5 mg/kg of A-127722 or vehicle (n=10 per group) intravenously 30 minutes and subcutaneously 4 hours after middle cerebral artery occlusion (MCAO). Whole-brain DWI and single-slice PI were done before initiation of treatment and repeated frequently thereafter up to 4 hours after MCAO. The animals were reperfused in the MRI scanner 90 minutes after the onset of MCAO. At 24 hours the animals were killed, and the brains were cut into six 2-mm-thick slices and stained with 2% TTC. Percent hemispheric lesion volume (%HLV) was calculated for each animal. RESULTS: Physiological parameters, body weight, neurological scores, and premature mortality (2 versus 2) did not differ between the two groups. No hypotension, abnormal behavior, or other adverse effects were seen. TTC-derived %HLV was 25.3+/-5.6% for controls and 16.2+/-9.6% for treated animals (36% reduction, P<.02). Six animals in each group had successful reperfusion as shown by PI. Among these animals, %HLV was 23.2+/-3.1% for controls and 9.3+/-4.4% for treated animals (60% reduction, P=.0001). The beneficial effect of A-127722 was limited to animals in which successful reperfusion was demonstrated. No difference in PI-detected perfusion deficit size was observed between the groups. DWI did not demonstrate significant in vivo lesion size differences. CONCLUSIONS: A-127722 significantly reduced ischemic lesion size in rats without observable adverse effects. It is not clear whether the effect was due to vasodilatation of collateral arterioles not detectable by PI or whether A-127722 has neuroprotective properties that are independent of vascular effects.

Acute Disease↗
PubMed1998

A new method to improve in-bore middle cerebral artery occlusion in rats: demonstration with diffusion- and perfusion-weighted imaging.

BACKGROUND AND PURPOSE: In-bore middle cerebral artery occlusion (MCAO) enables investigators to acquire preischemic MRI data and to image ischemic changes immediately after occlusion. We have developed a highly successful in-bore MCAO method. This study describes the methods and pertinent techniques. METHODS: Sixty-seven Sprague-Dawley rats were subjected to temporary (n=36) or permanent (n=31) MCAO. The occluding device consisted of a supporting tubing, a driving line, and a silicone-coated 4-0 nylon suture occluder. Outside the magnet, the occluder was positioned in the carotid canal. MCAO was achieved in the magnet bore by remotely advancing the driving line until resistance was felt. Diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) were acquired before and immediately after occlusion and were used to document the presence of MCAO. RESULTS: Fifty-nine (88.1%) rats were successfully occluded, demonstrating hyperintensity on DWI, perfusion deficits on PWI, and no subarachnoid hemorrhage at postmortem examination. The average values of the apparent diffusion coefficient in both the frontoparietal cortex and the lateral caudoputamen significantly decreased as early as 3 minutes after the onset of ischemia. The failures included preocclusion damage (1/67), sliding out of the occluder during occlusion (1/67), no occlusion (2/67), and arterial perforation (4/67). CONCLUSIONS: Our in-bore MCAO method is easily performed and is as successful as MCAO induced outside the magnet.

Animals↗
PubMed1998

Delayed treatment with an adenosine kinase inhibitor, GP683, attenuates infarct size in rats with temporary middle cerebral artery occlusion.

BACKGROUND AND PURPOSE: Brain ischemia is associated with a marked increase in extracellular adenosine levels. This results in activation of cell surface adenosine receptors and some degree of neuroprotection. Adenosine kinase is a key enzyme controlling adenosine metabolism. Inhibition of this enzyme enhances the levels of endogenous brain adenosine already elevated as a result of the ischemic episode. We studied a novel adenosine kinase inhibitor (AKI), GP683, in a rat focal ischemia model. METHODS: Four groups of 10 adult Sprague-Dawley rats were exposed to 90 minutes of temporary middle cerebral artery (MCA) occlusion. Animals were injected intraperitoneally with vehicle, 0.5 mg/kg, 1.0 mg/kg, or 2.0 mg/kg of GP683 30, 150, and 270 minutes after the induction of ischemia by a researcher blinded to treatment group. The animals were euthanatized 24 hours after MCA occlusion, and brains were stained with 2,3,5-triphenyltetrazolium chloride. We measured brain temperatures in a separate group of 6 rats before and after administration of 1.0 mg/kg GP683. RESULTS: All treated groups showed a reduction in infarct volumes, but a significant effect was observed only in the 1.0 mg/kg-dose group (44% reduction, P=0.0077). Body weight, physiological parameters, neurological scores, and mortality did not differ among the 4 groups. No apparent behavioral side effects were observed. Brain temperatures did not change after drug injection. CONCLUSIONS: Our results indicate that the use of AKIs offers therapeutic potential and may represent a novel approach to the treatment of acute brain ischemia. The therapeutic effect observed was not caused by a decrease in brain temperature.

Adenosine Kinase↗
PubMed1998

Efficacy of intra-arterial and intravenous prourokinase in an embolic stroke model evaluated by diffusion-perfusion magnetic resonance imaging.

OBJECTIVE: To explore the utility of intravenous (i.v.) prourokinase treatment, we compared intra-arterial (i.a.) and i.v. delivery in a rat embolic stroke model, using diffusion (DWI) and perfusion (PI) magnetic resonance imaging to assess in vivo effects on ischemic lesion evolution and reperfusion. BACKGROUND: Thrombolytic therapy with recombinant tissue-type plasminogen activator (rt-PA) for acute ischemic stroke is useful during the initial hours after onset. Prourokinase is a novel thrombolytic agent with potential safety advantages in comparison to rt-PA. METHODS: Twenty-four male Sprague-Dawley rats were embolized with autologous blood clots into the middle cerebral artery territory and then randomly assigned at 30 minutes after embolization to a 2-hour bolus infusion with i.a. prourokinase, i.v. prourokinase, or vehicle. DWI and PI were performed before treatment and repeated during and at the end of the treatment. RESULTS: PI demonstrated that both i.a. and i.v. significantly improved the percentage of the ischemic hemisphere that was normally perfused when the 20-minute, pretreatment, and 145-minute after embolization time points were compared; in the control group, the hypoperfused volume increased over time. DWI disclosed that the ischemic lesion evolution slightly decreased in the i.a. group, remained stable in the i.v. group, and increased over time in the control group. Infarct volume by triphenyltetrazolium chloride (TTC) staining was significantly smaller in both treatment groups than controls. CONCLUSIONS: These results demonstrate that i.a. and i.v. therapy with prourokinase are equally effective in promoting reperfusion and inhibiting the development of focal ischemic injury in this rat embolic stroke model.

Animals↗
PubMed1998

Course and outcome of chronic fatigue in children and adolescents.

PURPOSE: To describe the epidemiology, symptoms, and psychosocial characteristics of children and adolescents evaluated in a chronic fatigue program and determine the course and outcome of the syndrome in these patients. METHODS: During the summer of 1994, chart review was performed for the 58 patients evaluated between 1990 and 1994 and a telephone follow-up was conducted with 42 of the 58 families. Patients were predominantly female (71%) and white (94%), with 50% between the ages of 7 and 14 years and 50% between the ages of 15 and 21 years (mean age 14.6 years). RESULTS: At time of presentation, 50% of patients had been fatigued for 1 to 6 months and 50% had been fatigued for 7 to 36 months. Sixty percent indicated the fatigue had begun with an acute illness and 60% had a history of allergies. Most commonly reported symptoms were fatigue (100%), headache (74%), sore throat (59%), abdominal pain (48%), fever (36%), and difficulties with concentration and/or memory (33%). Most patients had a worsening of school performance and a decrease in social activities. On follow-up, there was significant improvement in many patients during the summer after the first visit, with continued improvement in most patients during the second and third years. At time of the follow-up telephone call, 43% of families considered their child "cured" and 52% considered their child "improved," whereas only 5% considered their child to be "the same." Statistical analyses demonstrated no demographic or clinical factors that distinguished between those who did or did not participate in the follow-up study, or between those who did or did not do well on follow-up. CONCLUSIONS: These data demonstrate that children and adolescents with chronic fatigue have a syndrome that is similar to that described in adults, but that the syndrome differs in several ways, most specifically, presentation earlier in the course of the illness and a more optimistic outcome.

Adolescent↗
PubMed1998

The use and cost of HIV service provision in England in 1996. National Prospective Monitoring System (NPMS) Steering Group and NPMS Working Party on Costs.

OBJECTIVE: The aim of the study was to measure the use and estimate the cost of HIV service provision in England. DESIGN AND SETTING: Standardised activity and case-severity data were collected prospectively in 10 English HIV clinics (5 London and 5 non-London sites) for the periods 1 January 1996 to 30 June 1996 and 1 July 1996 to 31 December 1996 and linked to unit cost data. In total, 5440 patients with HIV infection attended during the first 6 months and 5708 during the second 6 months in 1996. MAIN OUTCOME MEASURES AND RESULTS: The mean number of inpatient days per patient-year for patients with AIDS was 19.7 [95% confidence interval (CI): 13.7 to 25.7] for January to June and 20.8 (95% CI: 15.3 to 26.4) for July to December 1996. The mean number of outpatient visits for asymptomatic patients with HIV infection was 14.8 (95% CI: 11.9 to 17.6) and 13.3 (95% CI: 10.8 to 15.7) for the respective periods and 16.1 (95% CI: 13.21 to 18.97) and 15.7 (95% CI: 11.2 to 20.2), respectively, for patients with symptomatic non-AIDS (i.e. symptomatic patients with HIV infection but without AIDS-defining conditions). Substantial centre-to-centre variation was observed, suggesting that many clinics can continue the shift from an inpatient- to an outpatient-based service. Cost estimates per patient-year for HIV service provision for 1996 varied from 4695 Pounds (95% CI: 3769 Pounds to 5648 Pounds) for asymptomatic patients, to 7605 Pounds (95% CI: 6273 Pounds to 8909 Pounds) for symptomatic non-AIDS patients to 20,358 Pounds (95% CI: 17,681 Pounds to 23,206 Pounds) for patients with AIDS. CONCLUSIONS: Different combinations of antiretroviral therapy affect the cost estimates of HIV service provision differently. Anticipated reduction in inpatient-related activity through the increased use of combination antiretroviral therapy will further shift service provision from an inpatient- to outpatient-based service and reduce costs per patient-year. The extent and duration of such effects are currently unknown. The long term effects of combination treatment on the morbidity and mortality patterns of individuals infected with HIV are also currently unknown, as are their implications on the use and cost of HIV service provision. Multicentre databases like the National Prospective Monitoring System (NPMS) will provide healthcare professionals with information to improve existing services and anticipate the impact of new developments.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Nucleoside combinations for antiretroviral therapy: efficacy of stavudine in combination with either didanosine or lamivudine.

This paper reviews the results of three trials, HIV NAT002, AI455-053, and AIDS Clinical Trials Group (ACTG) 306, all of which evaluated the effectiveness of stavudine (d4T)-containing two-nucleoside combinations in antiretroviral-naive patients with human immunodeficiency virus type 1 (HIV-1) infection. The latter two studies directly compared d4T plus didanosine (ddI) or lamivudine (3TC) versus zidovudine (ZDV) plus each of these two nucleosides. The combined results of the three trials support the conclusion that d4T can be used effectively in combination with either ddI or 3TC to reduce viral loads and increase CD4 cell counts in patients with HIV-1 infection. The results of AI455-053 and ACTG 306 show further that combination of d4T with either ddI or 3TC is at least as effective as the use of ZDV with these nucleosides.

Adult↗
PubMed1998

Mental health care in a high school based health service.

This paper describes the mental health services provided at a high school based health center that integrates mental health and medical services. Five years after the inception of the center in 1988, mental health visits had quadrupled. In 1992 alone, students made 1,002 mental health visits. Strikingly, one-third of these students reported problematic substance use among other family members. Other leading reasons for utilizing mental health services included pregnancy (19%), past or present suicidal ideation (14%), obesity (8.7%), ongoing depression (8%), and issues related to sexuality (7.5%).

Adolescent↗
PubMed1998

Critical care--the worldwide perspective.

The development of the specialty of critical care and the intensivist is outlined and the data that favours critically ill patients being cared for by intensivists are reviewed. The future challenges for intensive and critical care are dealing with the new ethical dilemmas raised by intensive care, providing appropriate intensive care in both developed and developing countries and applying the principles of evidence-based medicine to intensive therapy.

Allied Health Personnel↗