Search PubMed⌕ Search

Biomedical subjects

M Fisher

Publications and source records attributed to M Fisher.

At least 37 records · Page 2Linked to original sources
PubMed2004

Noninvasive quantification of brain edema and the space-occupying effect in rat stroke models using magnetic resonance imaging.

BACKGROUND AND PURPOSE: Brain edema is a life-threatening consequence of stroke and leads to an extension of the affected tissue. The space-occupying effect due to brain edema can be quantified in rat stroke models with the use of MRI. The present study was performed to test 2 hypotheses: (1) Can quantification of the space-occupying effect due to brain edema serve as a noninvasive measure for brain water content? (2) Does morphometric assessment of brain swelling allow determination of true infarct size on MRI after correction for the space-occupying effect of edema? METHODS: Thirty rats were subjected to permanent suture middle cerebral artery occlusion. MRI was performed after 6 or 24 hours, and hemispheric swelling was assessed morphometrically. Interobserver and intraobserver agreements were determined for MRI measurements. In study I, the space-occupying effect due to brain edema was correlated with the absolute brain water content by the wet/dry method. In study II, lesion volumes corrected and uncorrected for edema were calculated on MRI and on TTC staining and compared. RESULTS: Interobserver and intraobserver agreements for MRI measurements were excellent (r>or=0.97). Brain water content and hemispheric swelling correlated well after 6 and 24 hours (r>or=0.95). Corrected lesion volumes correlated with r=0.78 between TTC staining and MRI. Without edema correction, lesion volumes were overestimated by 20.3% after 6 hours and by 29.6% after 24 hours of ischemia. CONCLUSIONS: Morphometric assessment of hemispheric swelling on MRI can determine the increase in absolute brain water content noninvasively and can also provide ischemic lesion volumes corrected for brain edema.

Animals↗
PubMed2004

Antitumor effects of bortezomib (PS-341) on primary effusion lymphomas.

Primary effusion lymphomas (PELs) are a rare type of non-Hodgkin's lymphoma that are resistant to cytotoxic chemotherapy. PELs manifest constitutive activation of nuclear factor kappa B (NF-kappaB), and inhibition of NF-kappaB induces apoptosis of PELs and sensitizes to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced death. Bortezomib (PS-341), a peptidyl boronic acid inhibitor of the proteasome, is a potent agent against a wide range of hematologic malignancies and has been shown to inhibit NF-kappaB. Thus, we examined the cytotoxic effects of bortezomib alone and in combination with various drugs. Bortezomib potently inhibited NF-kappaB in PEL cells in a dose-dependent manner. In addition, bortezomib inhibited growth and induced apoptosis of PEL cell lines (IC(50) values of 3.4-5.0 nM). Results of drug interactions between bortezomib and chemotherapy (doxorubicin and Taxol) were schedule-dependent: synergistic interactions were generally observed when PEL cells were pretreated with bortezomib prior to chemotherapy, whereas additive or even antagonistic interactions occurred with chemotherapy pretreatment or simultaneous treatment with bortezomib and chemotherapy. Most schedules of bortezomib and dexamethasone were synergistic, although pretreatment with dexamethasone resulted in additive interactions. Effects of combinations of bortezomib and TRAIL were generally additive. Thus, bortezomib represents a promising potential therapy for the treatment of PEL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

British HIV Association (BHIVA)/British Association for Sexual Health and HIV (BASHH) guidelines on provision of adherence support to individuals receiving antiretroviral therapy (2003).

The widespread use of highly active antiretroviral therapy (HAART) has dramatically reduced HIV-associated morbidity and mortality where treatment has been made available. Very high levels of adherence to HAART are a prerequisite for a successful virological and immunological response. Low adherence increases the risk of treatment failure and disease progression. It is also likely to lead to further transmission of resistant viruses, and to have a negative impact on the cost effectiveness of HAART. Low adherence is difficult to predict, and this has two key implications for service provision. Firstly, HAART should not be withheld on the basis of assumptions about adherence. Secondly, support with adherence should be provided to all patients prescribed HAART. Our understanding of barriers to and enablers of high adherence, and the evidence base regarding effective interventions, is limited. Meta-analysis of randomized controlled trials available from the general literature suggests multiple interventions are required to maintain high adherence to chronic therapy. This document recommends a series of measures for adoption within HIV clinical care settings, based on evaluation of existing data. High adherence is a process, not a single event, and therefore adherence support must be integrated into clinical follow up. Every prescribing unit should have a written policy on provision of adherence support, and ensure that staff are appropriately trained to make delivery of such services possible.

Anti-HIV Agents↗
PubMed2004

HMG CoA reductase inhibitors (statins): use in stroke prevention and outcome after stroke.

The use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) has been demonstrated to reduce the risk of primary and secondary ischemic stroke in patients with ischemic heart disease (relative risk reduction is 20-30%), confirmed by several prospective randomized placebo-controlled trials. At least one large prospective trial has also shown a similar benefit in patients without underlying ischemic heart disease. This is in contrast to an open-labeled trial conducted in the USA, which failed to demonstrate a significant benefit of statins in reducing stroke risk in hypertensive hyperlipidemic patients. It is less clear if treatment with statins before or after the onset of ischemic stroke also reduces its severity (improves outcome). Experimental animal studies where mice were pretreated with statins, demonstrated a reduced infarct size compared with untreated animals. Treatment with statins after stroke onset has also been demonstrated to enhance recovery without influencing infarct size (by increased angiogenesis, synaptogenesis and blood flow). A few clinical retrospective studies have demonstrated similar results. Prospective blinded placebo-controlled trials to test these findings are still lacking. This review discusses the various prospective trials in stroke prevention and available data on the effects of statins in improving outcome of established ischemic stroke. Alternate mechanisms of statins besides their lipid-lowering effect and relevance in reducing stroke risk and improving outcome are discussed. Finally, based on the present information, an evidence-based perspective about current and future use of statins in the short- and long-term management of ischemic stroke is presented.

Animals↗
PubMed2004

Effect of the WHI study on the attitude of Israeli gynecologists to hormonal therapy during menopause.

OBJECTIVE: To evaluate the attitude of Israeli gynecologists to the use of hormonal therapy (HT) during menopause consequent to the recent publication of the Women's Health Initiative (WHI) study. DESIGN: Gynecologists present at the annual convention of the Israeli Society of Obstetrics and Gynecology in the community were asked to complete a 5-item questionnaire on their opinions regarding hormone therapy (HT) use in light of the WHI study. RESULTS: Ninety-five percent of the physicians believed that HT is still a legitimate treatment modality during menopause, although almost 40% would now limit it to the management of climacteric symptoms. As a result of the WHI study, 65% of the physicians recommended cessation of HT use in up to 30% of their treated postmenopausal patients. The responders estimated that about 40% of their patients using HT ceased treatment on their own initiative following publication of the WHI study. CONCLUSIONS: Both physicians and patients were clearly influenced by the WHI study. Today, HT is being reserved by most gynecologists in Israel for the treatment of menopausal symptoms and is not being used as a preventive measure against future complications of heart disease and osteoporosis.

Attitude of Health Personnel↗
PubMed2003

Neuroprotective effects of MK-801 in different rat stroke models for permanent middle cerebral artery occlusion: adverse effects of hypothalamic damage and strategies for its avoidance.

BACKGROUND AND PURPOSE: Permanent middle cerebral artery occlusion (MCAO) with the use of the suture technique causes hypothalamic damage with subsequent hyperthermia, which can confound neuroprotective drug studies. In the present study the neuroprotective effects of dizocilpine (MK-801) were compared in different permanent MCAO models with and without hypothalamic damage and hyperthermia. METHODS: Sixty Sprague-Dawley rats were treated with MK-801 or placebo, beginning 15 minutes before MCAO, and assigned to the following groups: suture MCAO (group I), macrosphere MCAO without hypothalamic damage (group II), or macrosphere MCAO with intentionally induced hypothalamic infarction (group III). Body temperature was measured at 3, 6, and 24 hours. Lesion size was determined after 24 hours (2,3,5-triphenyltetrazolium chloride staining). RESULTS: Hypothalamic damage was present in animals in group I and was intentionally induced in group III with the use of a modified macrosphere MCAO technique. Body temperature was significantly increased 3, 6, and 24 hours after MCAO in these 2 groups of animals. Hypothalamic damage and subsequent hyperthermia could be avoided effectively by limiting the number of macrospheres (group II). MK-801 provided a highly significant neuroprotective effect in group II but not in groups I and III. CONCLUSIONS: Hypothalamic damage with subsequent hyperthermia masked the neuroprotective effect of MK-801. This side effect can be avoided by using the macrosphere MCAO technique with a limited number of spheres. This model therefore may be more appropriate to study the effects of neuroprotective drugs in permanent focal cerebral ischemia than the suture method.

Animals↗
PubMed2003

Multicenter study of human immunodeficiency virus-related germ cell tumors.

PURPOSE: Testicular germ cell tumors (GCT) occur at increased frequency in men with human immunodeficiency virus (HIV). This multicenter study addresses the characteristics of these tumors. PATIENTS AND METHODS: Patients with HIV-related GCT were identified from six HIV treatment centers. The incidence was calculated from the center with the most complete linked oncology and HIV databases. RESULTS: Thirty-five patients with HIV-related GCT were identified. The median age at GCT diagnosis was 34 years (range, 27 to 64 years). The median CD4 cell count was 315/mm3 (range, 90 to 960/mm3) at this time. The histologic classification was seminoma in 26 patients (74%) and nonseminomatous GCT in nine patients (26%). Twenty-one patients (60%) had stage I disease and 14 patients had metastatic disease. Overall six patients relapsed, three died from GCT, and seven died from HIV disease, resulting in a 2-year overall survival rate of 81%. HIV-related seminoma occurred more frequently than in the age- and sex-matched HIV-negative population, with a relative risk of 5.4 (95% confidence interval, 3.35 to 8.10); however, nonseminomatous GCT did not occur more frequently, and there was no change in the incidence of GCT since the introduction of highly active antiretroviral therapy. CONCLUSION: Testicular seminoma occurs significantly more frequently in HIV-positive men than in the matched control population. Patients with HIV-related GCTs present and should be treated in a similar manner to those in the HIV-negative population. After a median follow-up of 4.6 years, 9% of the patients died from GCT. Most of the mortality relates to HIV infection.

Adolescent↗
PubMed2003

Design of artificial transcription factors to selectively regulate the pro-apoptotic bax gene.

The tumor suppressor p53 is the most commonly mutated gene in human cancers. Active p53 is able to stimulate the transcription of a variety of genes including the pro-apoptotic gene bax, as well as p21, a cell cycle regulator. In this study we produced novel zinc finger transcription factors that would selectively increase the expression of bax, but not of other p53 targets. Reporter gene assays in p53-negative Saos-2 cells showed that the novel zinc finger proteins stimulated transcription driven by a minimal bax promoter, but not that driven by a minimal p21 promoter. Moreover, electromobility shift assays demonstrated that the novel transcription factors could bind the bax promoter sequence with high affinity and selectivity. Expression of a five zinc finger protein (5ZFAV) in COS-7 cells resulted in an increase in Bax protein levels, indicating that this novel transcription factor could act on endogenous gene expression. Expression of 5ZFAV also drastically reduced Saos-2 cell survival; this effect could be reversed by the general caspase inhibitor B-D-FMK. These data suggest that 5ZFAV is able to induce apoptosis through increased Bax expression. Further, while expression of 5ZFAV in p53-deficient Saos-2 cells reduced cell survival, there was little effect on U-2 OS cells which have wild-type p53. Thus the selective induction of the pro-apoptotic bax gene may be a valuable adjunct to cancer chemotherapy by diminishing survival of p53-deficient tumor cells.

Animals↗
PubMed2003

An open-label study of tenofovir in HIV-1 and Hepatitis B virus co-infected individuals.

BACKGROUND: Tenofovir is a novel nucleotide analogue recommended for use in HIV-1 infected treatment-experienced patients. Recent data suggest an effect on Hepatitis B virus (HBV) replication. We therefore investigated the use of tenofovir in HIV-1 and HBV co-infected individuals. METHODS: Twenty HIV-1/HBV co-infected patients with a median of 108 weeks lamivudine experience (range, 0-270 weeks) received tenofovir 245 mg daily in addition to or as part of their combination antiretroviral therapy. Their immunologic parameters and HIV-1 RNA and HBV DNA viral loads were followed over a period of 52 weeks. In addition, their HBV DNA polymerase was sequenced at baseline to measure the frequency of YMDD mutations that are associated with lamivudine resistance. FINDINGS: A significant decrease in HBV DNA viral load (4 x log ) and alanine aminotransferase levels was observed. There were no significant overall differences between the lamivudine-experienced (n = 15) and -naive (n = 5) individuals and tenofovir was well tolerated. Five patients (25%) underwent HBe antigen seroconversion during the study period. Out of the 15 lamivudine-experienced individuals, 10 had YMDD mutations and one had YIDD mutations in HBV DNA. INTERPRETATION: These results indicate that 52 weeks of tenofovir in addition to antiretroviral therapy is active against HBV, and it appears to overcome lamivudine resistance.

Adenine↗
PubMed2003

Adolescents and eating disorders: an examination of a day treatment program.

OBJECTIVE: In this study, we report on our day treatment program (DTP) for adolescents and young adults with eating disorders (EDs). METHOD: Data for the 82 female patients in DTP were examined, compared across ED diagnosis and by age (adolescents vs. young adults). At admission, patients completed the Eating Disorder Inventory-2 (EDI-2) and the Beck Depression Inventory (BDI) and the Family Adaptability and Cohesion Evaluation Scale- II (FACES-II). RESULTS: Forty-nine percent of patients successfully completed the day program and 13% required hospitalization following day treatment. Overall, there were no significant differences between the adolescents and adults at discharge of the day program. DISCUSSION: With shortened inpatient (IP) hospitalizations, DTPs can provide the long-term care required by many adolescent patients for psychological and physical recovery. This may be particularly important for the development of children and adolescents.

Adolescent↗
PubMed2003

Prediction of cardiovascular risk in people with diabetes.

People with diabetes are at high risk of cardiovascular morbidity and mortality, especially if they have already developed vascular problems. For patients who are apparently free of vascular complications, risk tables are often used to assess the risk of cardiovascular events in the following years, and to decide on treatment with statins or anti-platelet therapy. These risk prediction tables include estimates of traditional cardiovascular risk factors and are based on populations, some of which only contained a very small number of people with diabetes. Multiple problems can be identified with these tables, and many seriously underestimate cardiovascular risk in people with diabetes. Possible ways of addressing this include using risk estimation tools based solely on diabetic populations, adding in additional traditional variables such as triglycerides or left ventricular hypertrophy, including novel cardiovascular risk factors, or intervening at a lower level of estimated risk in people with diabetes compared with non-diabetic subjects. Alternatively, estimates of individual risk could be abandoned and all people with diabetes could be treated with statins and other effective agents.

Diabetes Mellitus↗
PubMed2003

Factors associated with a reduced CD4 lymphocyte count response to HAART despite full viral suppression in the EuroSIDA study.

OBJECTIVES: To describe the prevalence and risk factors of poor CD4 count rise despite a good virological response on highly active antiretroviral treatment (HAART). METHODS: The patients from the EuroSIDA study who started HAART with a baseline CD4 count of <350 cells/microL and where all viral load (pVL) measures remained below 500 HIV-1 RNA copies/mL between 6 and 12 months after the start of HAART were included. The risk factors for poor CD4 count rise were analyzed by multiple regression. RESULTS: Seven hundred and eighty patients were included. A low CD4 count response was observed in 225 patients (29%). The risk factors for this condition were older age, lower CD4 count at baseline, higher increase from the nadir to baseline CD4 count and lower pVL at baseline. Patients taking > or =one drug from each of the three antiviral classes were more likely to have a good CD4 response but a minority of the study participants was taking this treatment regimen (3.1%) and the confidence interval was large. CONCLUSIONS: A poor immune reconstitution despite a good virological control is frequent after initiation of HAART among patients with a baseline CD4 count of <350 cells/microL. The underlying mechanisms leading to this condition seems mainly driven by the age and the baseline immunological and virological status of the patients.

Adult↗
PubMed2003

Detection of frequency resonance energy transfer pair on double-labeled microsphere and Bacillus anthracis spores by flow cytometry.

Development of an ultrasensitive biosensor for biological hazards in the environment is a major need for pollutant control and for the detection of biological warfare. Fluorescence methods combined with immunodiagnostic methods are the most common. To minimize background noise, arising from the unspecific adsorption effect, we have adapted the FRET (frequency resonance energy transfer) effect to the immunofluorescence method. FRET will increase the selectivity of the diagnosis process by introducing a requirement for two different reporter molecules that have to label the antigen surface at a distance that will enable FRET. Utilizing the multiparameter capability of flow cytometry analysis to analyze the double-labeling/FRET immunostaining will lead to a highly selective and sensitive diagnostic method. This work examined the FRET interaction of fluorescence-labeled avidin molecules on biotin-coated microspheres as a model system. As target system, we have used labeled polyclonal antibodies on Bacillus anthracis spores. The antibodies used were purified immunoglobulin G (IgG) molecules raised in rabbits against B. anthracis exosoporium components. The antibodies were fluorescence labeled by a donor-acceptor chromophore pair, alexa488 as a donor and alexa594 as an acceptor. On labeling the spores with alexa488-IgG as a donor and alexa594-IgG as an acceptor, excitation at 488 nm results in quenching of the alexa-488 fluorescence (E(q) = 35%) and appearance of the alexa594 fluorescence (E(s) = 22%), as detected by flow cytometry analysis. The FRET effect leads to a further isolated gate (FL1/FL3) for the target spores compared to competitive spores such as B. thuringiensis subsp. israelensis and B. subtilis. This new approach, combining FRET labeling and flow cytometry analysis, improved the selectivity of the B. anthracis spores by a factor of 10 with respect to B. thuringiensis subsp. israelensis and a factor of 100 with respect to B. subtilis as control spores.

Antibodies, Bacterial↗
PubMed2003

Diabetes: can we stop the time bomb?

Type 2 diabetes is increasing in prevalence and it is estimated that three million individuals in the UK will have the disease by 2010. People with diabetes have a high risk of cardiovascular disease-coronary heart disease is more prevalent, more extensive, and more diffuse. For all cardiovascular syndromes, the mortality is virtually doubled in patients with diabetes. Large clinical trials have provided clear evidence of the reduction in cardiovascular risk that can be achieved by treating hyperglycaemia as well as traditional risk factors, such as hypertension and hyperlipidaemia. The challenge now is for all health care professionals to implement the treatment guidelines.

Anticholesteremic Agents↗
PubMed2003

Infection and risk of ischemic stroke: differences among stroke subtypes.

BACKGROUND AND PURPOSE: Although prior studies have demonstrated that 25% to 35% of stroke patients have had a recent infection, the role of infection as a risk factor remains unclear. Our aim was to characterize the effect of infectious/inflammatory syndromes on stroke risk. METHODS: Case-control and crossover analyses of 233 cases and 363 controls aged 21 to 89 years were performed. Cases were patients hospitalized with a first ischemic stroke at a Los Angeles, California, medical center. Controls were outpatients in the hypertension, diabetes, and general medical clinics. All subjects were administered a neurological examination, an infection/inflammation (I/I) examination, and an interview to elicit recent I/I history at baseline (within several days of stroke onset) and again approximately 2 months later. Three physicians classified subjects by the presence or absence of I/I within 1 month of the index dates, based on findings of the I/I examination, the interview report, and laboratory results. RESULTS: Infections, either total or specific, were not found more frequently in cases than controls. However, patients with a recent respiratory tract infection suffered more often from large-vessel atherothromboembolic or cardioembolic stroke than did patients without infection (48% vs 24%, P=0.07). The age- and sex-adjusted relative risk estimate for these subtypes was 1.75 (95% CI, 0.86 to 3.55). The risk was notably high for those without stroke risk factors: 4.15 (95% CI, 1.22 to 14.1) for normotensives, 2.71 (95% CI, 1.04 to 7.06) for nondiabetics, and 1.74 (95% CI, 0.74 to 4.07) for nonsmokers. Patients with a recent respiratory infection also had a more severe neurological deficit on admission than those without infection (P=0.05). CONCLUSIONS: Our results suggest that respiratory tract infection may act as a trigger and increase the risk of large-vessel and/or cardioembolic ischemic stroke, especially in those without vascular risk factors.

Adult↗
PubMed2003

Knowledge and attitude towards personal health care and menopause among women with ischemic heart disease undergoing coronary angiography.

The aim of this study was to assess the knowledge, perception, and attitude towards personal health care and menopause among women with ischemic heart disease. The study population consisted of 100 menopausal women attending the cardiac unit for coronary angiography. All women completed a 20-item questionnaire, covering information on health-care habits, life style and attitude towards menopause. About half of the study population had ever smoked, were overweight, had never tried to lose weight and did not exercise regularly. The majority regularly underwent screening mammography, Pap smear and lipid profile measurement. There was a positive statistically significant correlation between years of education and having annual mammography, Pap smear and lipid profile, performing breast self-examinations and taking an annual vacation. Sixty eight per cent of the study population had never used hormone replacement therapy (HRT), 13.2% had used HRT in the past and 18.8% were currently using HRT. There was a negative statistically significant correlation between use of HRT and age and number of children, and a positive statistically significant correlation between use of HRT and having an annual Pap smear and mammography scan. Only a relatively small percentage of the study population safeguarded their health care or used HRT. We believe that stronger efforts are needed to promote good health-related behaviors for these women.

Aged↗