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Biomedical subjects

M Fisher

Publications and source records attributed to M Fisher.

At least 271 records · Page 15Linked to original sources
PubMed1995

Potentially effective therapies for acute ischemic stroke.

Acute ischemic stroke remains without an effective therapy to improve outcome. As knowledge about the basic pathophysiology has expanded, rational approaches to therapy have evolved. The frequent presence of arterial occlusion suggested that thrombolytic therapy might be a viable approach. Both clot-specific and nonspecific thrombolytic agents are currently being evaluated in clinical trials. Focal brain ischemia induces a variety of cellular consequences. Neuroprotective therapies designed to ameliorate these metabolic abnormalities are also being evaluated in clinical trials. A key feature of all these clinical trials is the rapid initiation of therapy. In the future, we can anticipate combined therapy trials with both neuroprotective and thrombolytic drugs, an approach which is likely to be more beneficial than either one in isolation.

Acute Disease↗
PubMed1995

Comparison of a gonadotropin-releasing hormone agonist and a low dose oral contraceptive given alone or together in the treatment of hirsutism.

Chronic GnRH agonist therapy lowers androgens and decreases androgen-dependent hair shaft diameter, but the resulting induction of hypoestrogenemia has limited its usefulness as a single agent. Estrogen- and progestin-containing oral contraceptives also reduce circulating androgen levels and are commonly used empirically for the treatment of hirsutism, but have not been evaluated in a blinded randomized controlled fashion. The present study is the first double masked trial to evaluate the combination use of a GnRH agonist and an estrogen-containing oral contraceptive and tests our hypothesis that these could synergistically reduce androgen levels and suppress hormone-dependent hair growth while avoiding the symptoms and risks of agonist-induced hypoestrogenemia. We enrolled 64 women in a 24-week blinded randomized controlled trial to compare placebo, nafarelin (NAF; 400 micrograms, intranasal spray, twice daily), norethindrone (1 mg), and ethinyl estradiol (NOR 1/35; 0.035 mg, daily, for 3 of 4 weeks), or combined use of NAF and NOR 1/35 for 24 weeks. At baseline and every 8 weeks, we measured gonadotropins, estrogens, androgens, and hair growth. Bone density was assessed by dual energy x-ray adsorptiometry, and hot flashes were measured objectively. Baseline total testosterone (T), free T, percent free T, and sex hormone-binding globulin-binding capacity were similar among groups. With treatment, significant reductions (P = 0.01) in total T were seen with combination and NAF only therapy. Significant increases (P < 0.001) in the sex hormone-binding globulin-binding capacity were seen in women given NOR 1/35 alone or in combination with NAF. Free T levels decreased to approximately half of baseline levels with combination treatment (17.9 to 6.4 nmol/L; P < 0.001) and NOR 1/35 alone (20.8 to 10.2 nmol/L; P < 0.001). There was a significant decrease in hair shaft diameter after combination therapy (P < 0.05) that was not seen with either agent alone. Combination therapy also prevented the hot flashes and bone loss that occurred with agonist alone. In summary, our results demonstrate that combination GnRH agonist and low dose oral contraceptive therapy is more effective than either agent alone in the treatment of hirsutism and avoids the hypoestrogenic complications that occur with agonist only therapy.

Adult↗
PubMed1995

Multislice diffusion mapping for 3-D evolution of cerebral ischemia in a rat stroke model.

Diffusion-weighted magnetic resonance imaging (DWI) can quantitatively demonstrate cerebral ischemia within minutes after the onset of ischemia. The use of a DWI echo-planar multislice technique in this study and the mapping of the apparent diffusion coefficient (ADC) of water, a reliable indicator of ischemic regions, allow for the detection of the three-dimensional (3-D) evolution of ischemia in a rat stroke model. We evaluated 13 time points from 5 to 180 minutes after occlusion of the middle cerebral artery (MCA) and monitored the 3-D spread of ischemia. Within 5 minutes after the onset of ischemia, regions with reduced ADC values occurred. The core of the lesion, with the lowest absolute ADC values, first appeared in the lateral caudoputamen and frontoparietal cortex, then spread to adjacent areas. The volume of ischemic tissue was 224 +/- 48.5 mm3 (mean +/- SEM) after 180 minutes, ranging from 92 to 320 mm3, and this correlated well with the corrected infarct volume at postmortem (194 +/- 23.1 mm3, r = 0.72, p < 0.05). This experiment demonstrated that 3-D multislice diffusion mapping can detect ischemic regions noninvasively 5 minutes after MCA occlusion and follow the development of ischemia. The distribution of changes in absolute ADC values within the ischemic region can be followed over time, giving important information about the evolution of focal ischemia.

Animals↗
PubMed1995

Elective intubation for neurologic deterioration after stroke.

OBJECTIVE: To provide data to guide physicians and family when deciding whether a patient should be electively intubated after ischemic stroke. DESIGN: Chart review and patient interview. Clinical course, neurologic outcome, and financial and psychosocial effect of the decision to intubate were determined. SETTING: Neurology/Neurosurgery critical care unit. PATIENTS: Of our last 250 acute carotid territory ischemic stroke cases, we found 20 patients (8%) who were electively intubated, after CT and neurologic assessment, for neurologic deterioration. INTERVENTIONS: All patients received standard medical therapy. RESULTS: Intubation occurred 3 hours to 7 days (mean, 41 hours) after the onset of symptoms; six of 20 patients required intubation within the first 6 hours. Once clinical deterioration began, 10 of 20 patients required intubation within 1 hour. Six of 20 patients were discharged alive; two subsequently died, one is mostly dependent, two became mostly independent (one of these had a hemicraniectomy and is still improving, and the other died of an intercurrent illness 4 years after her stroke), and one is totally independent. The four "good" outcome survivors were distinguished by higher Glasgow Coma Scale scores (9.2 versus 5.9), and extubation was usually possible within 72 hours. For nonsurvivors, mean hospitalization after intubation was 6.4 days. In survivors, the monthly uninsured cost was $0 to $2,000, and caregivers experienced moderate stress. The same decision would be repeated by 76% of caregivers; 53% of caregivers would want intubation for themselves. CONCLUSIONS: Satisfactory outcome is possible in the 8% of ischemic stroke patients requiring elective intubation. Possible predictors of good outcome include less severe depression of consciousness at the time of intubation, extubation within 3 days, and hemicraniectomy. In retrospect, most families would repeat the decision to intubate. Further study in more patients of the cost/benefit of cerebral resuscitation after stroke is greatly needed.

Adult↗
PubMed1995

An unusual gastrointestinal presentation of leishmaniasis.

While visceral leishmaniasis (VL) generally occurs in immunocompetent subjects in endemic areas, it has been increasingly recognised as an important opportunistic infection in the immunocompromised including those infected with the human immunodeficiency virus. We report an unusual presentation of visceral leishmaniasis in a patient with the acquired immunodeficiency syndrome (AIDS) with disease which appeared to be limited to the gastrointestinal tract.

AIDS-Related Opportunistic Infections↗
PubMed1995

The penumbra, therapeutic time window and acute ischaemic stroke.

There is a great deal of evidence that an ischaemic penumbra exists in animals and humans after the occurrence of focal brain ischaemia (Hossmann, 1994). The concept of the penumbra leads to the idea of a therapeutic time window. Because, if the region of irreversible injury (infarction) after focal ischaemia evolves in time and space, then the possibility of therapy to interfere becomes a tenable hypothesis. All of the acute stroke therapies given after onset have their basis from this hypothesis of a therapeutic time window (Fisher, 1995). As previously alluded to, a more apt term might be a window-shade, because this metaphor suggests a more dynamic event. The time and location of potentially salvageable ischaemic brain tissue after ischaemic stroke is a moving target and many unanswered questions remain. The data from animal stroke models support 2-3 hours as the time when intervention is likely to be beneficial in rats. Non-human primate data are scarce, but the few studies available do imply that at 3-4 hours after stroke onset some ischaemic tissue remains potentially salvageable. In humans, we really do not know what the time window is and we must remember that it is likely to be highly variable among individuals. This variability relates to many factors including the status of collateral flow, patient age, coexistent metabolic abnormalities (i.e. hyperglycaemia), premorbid medications and many other confounding variables. All acute stroke intervention trials are trying to initiate therapy within 6-8 hours after onset and the earlier, presumably the better. However, this approach is based upon population averaging, since we have had no convenient and reliable mechanism to determine, if an individual patient has viable tissue when therapy can be started. The availability of an imaging modality that could distinguish the presence and extent of salvageable ischaemic tissue would greatly facilitate stroke therapy trials and ultimately the selection of patients when proven therapies are available. The new MRI techniques might afford this possibility. As we enter the exciting era of effective therapy for acute ischaemic stroke, the issues surrounding the therapeutic time window(shade) will become more critical, because it is this critical time that will define the success or failure of our interventions. Therefore it is incumbent upon basic stroke researchers and clinicians to continue to define the ischaemic penumbra and to develop readily applicable mechanisms to identify and treat this moving target.

Animals↗
PubMed1995

Psychosocial variables associated with teenage pregnancy.

This study investigated whether psychosocial factors differentiate sexually active teenagers who become pregnant from those who do not. Data were collected from 64 unmarried adolescents who attended a suburban health clinic for a pregnancy test or for contraceptive care. Thirty-nine percent of the sample had been or were now pregnant, and 61% had never been pregnant. Each teenager completed a questionnaire and three self-report measures (Life Events Checklist, Self-Worth, Health Locus of Control) prior to her medical visit. Information about family, medical, and psychosocial history was obtained from chart review. When girls who had positive pregnancy tests, and sexually active girls who had never been pregnant were compared, no significant differences emerged on socioeconomic status, race, religion, age or psychological variables. However, when adolescents with a previous or current history of pregnancy (N = 25) were compared with girls who had never been pregnant (N = 39), using the Mann Whitney test, two significant differences were found: adolescents with a history of pregnancy had first intercourse at the mean age of 15 rather than 16 (p < .02) and scored higher than never-pregnant teenagers on the "Powerful Other" Health Locus of Control subscale, a measure of strong belief in external control by others (p < .01). No significant differences were detected between the groups for self-worth or life events perceived as stressful during the past year. These data indicate that in a middle-class suburban population of sexually active teenagers, earlier age at first intercourse and the influence of powerful others are important variables associated with pregnancy.

Adolescent↗
PubMed1995

Molecular analysis of HLA class II genes in Goodpasture's disease.

A molecular analysis of HLA class II genes was undertaken in order to characterize the previously reported association between HLA-DR2 and glomerulonephritis caused by antibodies to glomerular basement membrane (Goodpasture's disease). Genomic DNA was prepared from 53 patients with Goodpasture's disease and analysed by: (i) Southern blotting using cDNA probes to DRB, DQA and DQB genes, after digestion with TaqI endonuclease; (ii) allele-specific oligonucleotide probing of specifically amplified DNA; and (iii) nucleotide sequencing of relevant alleles. The patients had a greatly increased frequency of DRw15 (a subspecificity of DR2) which was present in 75.5% of patients and 31% of controls (p < 0.0001). The frequency of DR4 was also increased, especially in patients without DRw15. Overall, 90.5% of the patients had either DRw15 or DR4. In contrast, the frequency of DR1 was significantly reduced (patients 5.6%, controls 20.7%, p < 0.01). Differences in the frequencies of DQA and DQB alleles could all be explained by linkage disequilibrium. Nucleotide sequences of relevant alleles were identical to those previously published. Comparison of derived amino acid sequences of expressed DR beta chains showed that the DR beta chains of DRw15 and DR4 shared a six-amino-acid motif from positions 26-31, that included four polymorphic amino acids none of which are shared with DR1. A sequence-specific oligonucleotide detected this amino-acid motif in 45/49 (91.8%) patients tested. Thus, this particular motif, which lies on the floor of the antigen binding groove, has a stronger association with Goodpasture's disease than any individual allele, and may be of pathogenic significance.

Alleles↗
PubMed1995

Back to school: training opportunities in school-based health centers.

School-based health centers are a rapidly growing model for provision of comprehensive, primary health care to elementary, middle, and senior high school students. They offer an exciting new training opportunity that is nontraditional, multidisciplinary, and relevant to future practice. The programs funded by the Robert Wood Johnson Foundation found that trainees made a significant contribution to their projects. The value of school-based health centers as training sites extends to trainees, schools, and the future growth of school-based health centers. Integration of medical and mental health services and delivery of services by a multidisciplinary team are essential components of school-based health centers. These characteristics make school sites well suited to the training needs and practice opportunities sought by a number of disciplines, including developmental and behavioral pediatrics. A school-based health center rotation may be particularly important in developmental and behavioral pediatrics because many trainees may be called on to consult with schools in their future careers, and this rotation may provide their only school-related experience.

Education↗
PubMed1994

The effects of blinding on acceptance of research papers by peer review.

OBJECTIVE: To study whether reviewers aware of author identity are biased in favor of authors with more previous publications. DESIGN: Randomized controlled trial. SETTING: Editorial office of the Journal of Developmental and Behavioral Pediatrics. PARTICIPANTS: Two "blinded" and two "nonblinded" reviewers assigned to 57 consecutive manuscripts submitted between September 1991 and March 1992. OUTCOME MEASURES: Spearman rank correlation coefficients were used to compare the sum of rating scores of 1 to 5 (1, accept; 5, reject) given by the two blinded reviewers, the two nonblinded reviewers, and the editors to the number of articles published previously by the first and senior authors (as determined from requested curricula vitae). Blinded reviewers were sent a questionnaire asking whether they could determine the identity of the authors, how they knew, and whether they thought binding changed the quality or difficulty of their review. RESULTS: The Wilcoxon Sign Rank Test disclosed no differences between blinded and nonblinded scores. The number of previous articles by the senior author was significantly correlated (P < .01) with blinded scores (r = -.45) and editors' decisions (r = -.45), but not with nonblinded scores; the number of articles by the first author was correlated (P < .05) with editors' decisions (r = -.35) but not with blinded or nonblinded scores. Fifty (46%) of 108 blinded reviewers correctly guessed the identity of the authors, mostly from self-references and knowledge of the work; 86% believed blinding did not change the quality of their review, and 73% believed it did not change the difficulty of performing a review. CONCLUSIONS: Blinded reviewers and editors in this study, but not nonblinded reviewers, gave better scores to authors with more previous articles. These results suggest that blinded reviewers may provide more unbiased reviews and that nonblinded reviewers may be affected by various types of bias.

Authorship↗