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M White

Publications and source records attributed to M White.

At least 73 records · Page 4Linked to original sources
PubMed2001

Orexin a preferentially excites glucose-sensitive neurons in the lateral hypothalamus of the rat in vitro.

Falls in blood glucose induce hunger and initiate feeding. The lateral hypothalamic area (LHA) contains glucose-sensitive neurons (GSNs) and orexin neurons, both of which are stimulated by falling blood glucose and are implicated in hypoglycemia-induced feeding. We combined intracellular electrophysiological recording with fluorescein labeling of GSNs to determine their neuroanatomic and functional relationships with orexin neurons. Orexin A (1 micromol/l) caused a 500% increase (P < 0.01) in spontaneous firing rate and rapid and lasting depolarization that was tetrodotoxin-resistant and thus a direct postsynaptic effect. Orexin A altered the intrinsic neuronal properties of GSNs, consistent with increased excitability. Confocal microscopy showed that GSNs were intimately related to orexin neurons: orexin-immunoreactive axons were frequently entwined around GSN dendrites, establishing close and putatively synaptic contacts. Orexin-cell axons also passed in close proximity to glucose-responsive neurons, which are inhibited by low glucose, but orexin A caused smaller depolarization than on GSNs and only a 200% increase in spontaneous firing rate (P < 0.05 vs. GSN). We conclude that GSNs are specific target neurons for orexin A and suggest that they may mediate, at least in part, the acute appetite-stimulating effect of orexin A. Orexin neurons may regulate GSNs so as to control the onset and termination of hypoglycemia-induced feeding.

Animals↗
PubMed2001

Neutrophil survival is markedly reduced by incubation with influenza virus and Streptococcus pneumoniae: role of respiratory burst.

Bacterial superinfections are an important cause of morbidity and mortality during influenza A virus (IAV) epidemics. We demonstrate that incubation with the combination of IAV and Streptococcus pneumoniae caused marked reductions in survival of neutrophils in vitro compared with treatment with control buffer or IAV or S. pneumoniae alone. This cooperative effect was in part mediated by acceleration of neutrophil apoptosis as evidenced by increases in annexin-V binding and caspase-3 activation. However, GM-CSF did not increase survival of neutrophils exposed to IAV and S. pneumoniae. IAV enhanced neutrophil uptake of S. pneumoniae significantly. Furthermore, the combination of IAV and S. pneumoniae caused significantly more hydrogen peroxide production than IAV or S. pneumoniae alone. This increased respiratory burst activity contributed to the diminished neutrophil survival caused by IAV and S. pneumoniae. The NADPH oxidase inhibitor, diphenyleneiodonium, significantly improved survival of neutrophils treated with IAV and S. pneumoniae. These findings may help to explain the increased susceptibility of IAV-infected patients to infections with S. pneumoniae.

Cell Survival↗
PubMed2001

Comparison of 2-dimensional and 3-dimensional cardiac 82Rb PET studies.

UNLABELLED: Most new PET scanners have the capability to collect data in 3-dimensional (3D) (septa removed) mode. This allows many more detected events at the cost of increased random events and scatter. In the case of 82Rb imaging, the injected dose might have to be limited to avoid saturating the scanner. We present a comparison of 2-dimensional (2D) and 3D data collection for 82Rb cardiac studies using the ECAT EXACT scanner. METHODS: Resting 82Rb cardiac studies were collected in 2D and 3D modes for 33 consecutive patients. Four experienced physicians rated the images to determine if the different acquisition methods would lead to different patient care. A separate quantitative analysis was performed on data from multiple scans of a thoracic phantom filled to simulate cardiac and background radioactivity corresponding to 82Rb injections between 37 and 1740 MBQ: RESULTS: The 2D and 3D studies were significantly different, with the image quality being poorer in the 3D studies. The scanner collected data at near its maximal counting rate for either 1480-MBq 2D or 37-MBq 3D acquisitions. Because the data collection was counting rate limited in either mode, and there are more random and scatter events in 3D mode, the 2D acquisitions resulted in more detected true events and a better signal-to-noise ratio. CONCLUSION: Cardiac 82Rb studies should be performed in 2D mode when using the ECAT EXACT scanner.

Heart↗
PubMed2001

Nasal meningioma: report of one case and review.

A case of primary nasal meningioma in a 69-year-old women is described. The pathologic, radiologic and clinical characteristics are described. A summary of previously published articles on the subject is given.

Aged↗
PubMed2001

Financial performance and participation in Medicaid and Medi-Cal managed care.

This article assesses the participation and the financial performance of licensed health maintenance organization (HMOs) in the Medicaid market. The study found that participation by Medicaid Dominant plans has more than doubled from 11 percent in 1992 to 23 percent in 1998 while Medicaid membership in Commercial Dominant plans declined from 71 percent in 1994 to 51 percent in 1998. Both participating and non-participating plans incurred operating losses in 1998. Medi-Cal participating plans had higher operating margins than Medicaid participating plans throughout the United States. Interviews with key informants express concern about competence in program management, rate adequacy, decline in Medicaid enrollment, and turbulence forces of managed care market on Medicaid programs.

California↗
PubMed2000

Comparison of TP53 mutations identified by oligonucleotide microarray and conventional DNA sequence analysis.

As the rate of gene discovery accelerates, more efficient methods are needed to analyze genes in human tissues. To assess the efficiency, sensitivity, and specificity of different methods, alterations of TP53 were independently evaluated in 108 ovarian tumors by conventional DNA sequence analysis and oligonucleotide microarray (p53 GeneChip). All mutations identified by oligonucleotide microarray and all disagreements with conventional gel-based DNA sequence analysis were confirmed by re-analysis with manual and automated dideoxy DNA sequencing. A total of 77 ovarian cancers were identified as having TP53 mutations by one of the two approaches, 71 by microarray and 63 by gel-based DNA sequence analysis. The same mutation was identified in 57 ovarian cancers, and the same wild type TP53 sequence was observed in 31 ovarian cancers by both methods, for a concordance rate of 81%. Among the mutation analyses discordant by these methods for TP53 sequence were 14 cases identified as mutated by microarray but not by conventional DNA sequence analysis and 6 cases identified as mutated by conventional DNA sequence analysis but not by microarray. Overall, the oligonucleotide microarray demonstrated a 94% accuracy rate, a 92% sensitivity, and an 100% specificity. Conventional DNA sequence analysis demonstrated an 87% accuracy rate, 82% sensitivity, and a 100% specificity. Patients with TP53 mutations had significantly shorter overall survival than those with no mutation (P = 0.02). Women with mutations in loop2, loop3, or the loop-sheet-helix domain had shorter survival than women with other mutations or women with no mutations (P = 0.01). Although further refinement would be helpful to improve the detection of certain types of TPS3 alterations, oligonucleotide microarrays were shown to be a powerful and effective tool for TP53 mutation detection.

Female↗
PubMed2000

Factors influencing alcohol and illicit drug use amongst medical students.

Alcohol, illicit drug use, and other lifestyle variables, as well as stress, anxiety and personality were evaluated in 194 first year medical students. 45% of the students reported drinking above the recommended UK limits for alcohol consumption. The age at which the first full drink of alcohol was taken was predictive of the current level of alcohol use. Cannabis was the most frequently used illicit drug (45%). There were significant positive associations between alcohol consumption and experiences such as missing study, becoming more sexually involved and getting into a physical fight or argument. There were also significant positive associations between the personality characteristic of psychoticism and alcohol and illicit drug consumption. The effectiveness of current health education on alcohol and illicit drugs is questioned.

Adolescent↗
PubMed2000

Identification of coronary thrombus with a IIb/IIIa platelet inhibitor radiopharmaceutical, technetium-99m DMP-444: A canine model.

BACKGROUND: A diagnostic test that could distinguish between stable and unstable coronary atherosclerotic plaques would be useful. We tested the ability of a new glycoprotein IIb/IIIa platelet inhibitor DMP-444, labeled with technetium (Tc)-99 m, to identify platelet-rich thrombus by nuclear imaging in a canine model. METHODS AND RESULTS: Combinations of a flow-limiting stenosis and 0 to 15 minutes of endothelial electrical stimulation at a site in the left anterior descending coronary artery were used to induce varying amounts of thrombus formation. In 10 animals with markedly positive nuclear images after the injection of Tc-99m DMP-444, the presence of platelet-rich thrombus was confirmed postmortem by gross appearance, high nuclear counts, and abundant platelets on electron microscopy. The 10 animals with negative images had lower counts, smaller thrombus weights (P<0.05 for each), and fewer platelets by electron microscopy. CONCLUSIONS: Activated platelets participating in acute thrombus formation can be accurately detected by nuclear imaging using Tc-99 m DMP-444.

Animals↗
PubMed2000

Prolongation of xenograft survival using monoclonal antibody CD45RB and cyclophosphamide in rat-to-mouse kidney and heart transplant models.

BACKGROUND: Intrigued by the finding that a monoclonal antibody (mAb) directed against the B exon of restricted CD45 (CD45RB mAb) induced renal allograft tolerance in the mouse model, we hypothesized that CD45RB mAb may prevent xenograft rejection. We explored the role of CD45RB mAb in preventing xenograft rejection in rat-to-mouse kidney and heart transplant models. METHODS: Mice with rat kidney and heart xenografts were treated with a short course of mAb, cyclosporine, cyclophosphamide, or mAb + cyclophosphamide combination therapy. Untreated heart and kidney xenografts served as controls. RESULTS: Untreated controls developed acute vascular and cellular rejection rapidly with a median survival time of only 6 days. Long-term kidney (median survival time = 70 days) and heart xenograft survival (median survival time = 65 days) was achieved using the combination therapy of mAb + cyclophosphamide. One-third of the kidney recipients with combination therapy survived 100 days. Immunohistochemistry and xenospecific-antibody analysis demonstrated that combination therapy remarkably reduced IgG and IgM deposition and also inhibited CD4+, CD8+, and Mac-1+ cell infiltration at early stages. This therapy, however, did not induce tolerance in this model as evoked xenoreactive antibodies and cellular responses may be the cause of late xenograft failure. CONCLUSION: A short course of CD45RB mAb combined with cyclophosphamide effectively inhibits cellular and humoral immunoresponses and remarkably prolongs xenograft survival in rat-to-mouse heart and kidney transplant models.

Animals↗
PubMed2000

Risk of cardiovascular disease measured by carotid intima-media thickness at age 49-51: lifecourse study.

OBJECTIVE: To quantify the direct and indirect effects of fetal life, childhood, and adult life on risk of cardiovascular disease at age 49-51 years. DESIGN: Follow up study of the "Newcastle thousand families" birth cohort established in 1947. PARTICIPANTS: 154 men and 193 women who completed a health and lifestyle questionnaire and attended for clinical examination between October 1996 and December 1998. MAIN OUTCOME MEASURES: Correlations between mean intima-media thickness of the carotid artery (carotid intima-media thickness) and family history, birth weight, and socioeconomic position around birth; socioeconomic position, growth, illness, and adverse life events in childhood; and adult socioeconomic position, lifestyle, and biological risk markers. Proportions of variance in carotid intima-media thickness that were accounted for by each stage of the lifecourse. RESULTS: Socioeconomic position at birth and birth weight were negatively associated with carotid intima-media thickness, although only social class at birth in women was a statistically significant covariate independent of adult lifestyle. These early life variables accounted directly for 2.2% of total variance in men and 2.0% in women. More variation in carotid intima-media thickness was explained by adult socioeconomic position and lifestyle, which accounted directly and indirectly for 3.4% of variance in men (95% confidence interval 0.5% to 6.2%) and 7.6% in women (2.1% to 13.0%). Biological risk markers measured in adulthood independently accounted for a further 9.5% of variance in men (2.4% to 14.2%) and 4.9% in women (1.6% to 7.4%). CONCLUSIONS: Adult lifestyle and biological risk markers were the most important determinants of the cardiovascular health of the study members of the Newcastle thousand families cohort at age 49-51 years. The limited overall effect of early life factors may reflect the postwar birth year of this cohort.

Cardiovascular Diseases↗
PubMed2000

Effects of administration of a single dose of a humanized monoclonal antibody to CD11a on the immunobiology and clinical activity of psoriasis.

BACKGROUND: CD11a/CD18 comprise subunits of leukocyte function associated antigen (LFA-1), a T-cell surface molecule important in T-cell activation, T-cell emigration into skin, and cytotoxic T-cell function. OBJECTIVE: We explored the immunobiologic and clinical effects of treating moderate to severe psoriasis vulgaris with a single dose of humanized monoclonal antibody against CD11a (hu1124). METHODS: This was an open label study with a single dose of hu1124 at doses of 0.03 to 10 mg/kg. Clinical (Psoriasis Area and Severity Index [PASI]) and immunohistologic parameters (epidermal thickness, epidermal and dermal T-cell numbers, and keratinocyte intercellular adhesion molecule 1 [ICAM-1] expression) were followed. RESULTS: Treatment with hu1124, at doses higher than 1.0 mg/kg (group III), completely blocks CD11a staining for at least 14 days in both blood and psoriatic plaques. At 0.3 to 1.0 mg/kg, T-cell CD11a staining was completely blocked; however, blockade lasted less than 2 weeks (group II). Only partial saturation of either blood or plaque cellular CD11a was observed at doses of hu1124 between 0.01 and 0.1 mg/kg (group I). This pharmacodynamic response was accompanied by decreased numbers of epidermal and dermal CD3(+) T cells, decreased keratinocyte and blood vessel expression of ICAM-1, and epidermal thinning. Statistically significant drops in PASI compared with baseline were observed in group II patients at weeks 3 and 4 and in group III patients at weeks 2 through 10. No significant drop in PASI score was observed in group 1. Adverse events were mild at doses of 0.3 mg/kg or less and included mild chills, abdominal discomfort, headache, and fever. At a single dose of 0.6 mg/kg or higher, headache was the most common dose-limiting toxicity observed. CONCLUSION: Targeting CD11a may improve psoriasis by inhibiting T-cell activation, T-cell emigration into the skin, and cytotoxic T-cell function.

Antibodies, Monoclonal↗
PubMed2000

Ten-year follow-up of critically ill patients undergoing heart transplantation.

BACKGROUND: The long-term result following heart transplantation appears very good despite complications of coronary atherosclerosis and cancer. Critically ill patients supported with mechanical devices remain a growing and difficult group in which long-term results need to be defined. The objective of this study was to review the 10-year follow-up of critically ill patients who underwent heart transplantation after support with mechanical devices. METHODS: We retrospectively analyzed all patients who underwent heart transplantation from 1986 to 1999 at the Montreal Heart Institute. RESULTS: Twenty-two patients (22/199, 11%) underwent heart transplantation after support with intra-aortic balloon pumps (n = 17) and total artificial hearts (n = 5). One hundred seventy-seven patients (177/199, 89%) underwent heart transplantation without pre-operative mechanical assistance. Patients with pre-operative mechanical assistance were younger (41 +/- 12 vs 48 +/- 10 years old, p = 0. 002), underwent a shorter waiting time to transplantation (2 +/- 2 vs 19 +/- 27 weeks, p = 0.004), and donor hearts had longer ischemic time (166 +/- 63 vs 137 +/- 49 minutes, p = 0.002) compared with patients without pre-operative mechanical assistance. One-month, 1-, 5-, and 10-year survival averaged 86% +/- 7%, 67% +/- 10%, 67% +/- 10%, and 59% +/- 12%, respectively, in patients with pre-operative mechanical assistance compared with 95% +/- 2%, 88% +/- 2%, 81% +/- 3%, and 74% +/- 4%, respectively, in patients without assistance, a significant difference (p = 0.04) that is mainly related to higher operative mortality in the former group. Although, we found no difference between the 2 groups in the 10-year freedom rate from acute rejection, infection, cancer, and coronary atherosclerosis, sepsis was the cause of 4 early deaths among patients with pre-operative mechanical assistance. CONCLUSION: Early and long-term survival was significantly decreased in critically ill patients with pre-operative mechanical assistance compared with other patients without pre-operative assistance. Sepsis is a dominant threat among patients who underwent heart transplantation with pre-operative mechanical assistance, and the lower survival is due mainly to the increased early mortality.

Adult↗
PubMed2000

Neuropsychologic and neuropsychiatric characteristics of patients with Friedreich's ataxia.

UNLABELLED: OBJECTIVES AND MATERIALS AND METHODS: Due to recent evidence of frontal-lobe related dysfunctions in patients with cerebellar atrophy, patients with Friedreich's ataxia were compared to normal subjects controlled for age, gender, and educational level on tests measuring information processing speed, visuospatial organization, selective attention, executive functions, and mood. RESULTS: Patients with Friedreich's ataxia had slowed information speed, as indicated by lengthened simple visual reaction time and increased color-word interference in the Stroop task. However, the patient group was not impaired in several tests sensitive to neocortical and particularly prefrontal cortex lesions, including an untimed version of block design, verbal fluency, Wisconsin card sorting, Tower of Hanoi, and picture arrangement. Despite serious sensorimotor dysfunctions, the patient group did not differ from controls in terms of mood, as evaluated by the Symptoms Checklist (SCL-90) and the Hamilton depression scale. CONCLUSION: These results indicate that the slowed information processing speed of patients with Friedreich's ataxia is not accompanied by major prefrontal cortex and mood disorders.

Adolescent↗
PubMed2000

Human herpesvirus 8 (KSHV) contamination of peripheral blood and autograft products from multiple myeloma patients.

Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV), has recently been identified within the bone marrow dendritic cells of multiple myeloma (MM) patients. This virus contains homologues to human cytokines such as IL-6 that could potentially stimulate myeloma cell growth and contribute to disease pathogenesis. Since mobilization chemotherapy may increase circulating dendritic cell numbers, we searched for HHV-8 in peripheral blood mononuclear cells (PBMCs) before and after mobilization chemotherapy given to MM patients. Furthermore, we determined if autograft purging using the CEPRATE SC device would reduce the percentage of HHV-8 infected stem cell products. Only two of the 39 PBMC samples collected prior to mobilization chemotherapy contained PCR detectable virus, yet nine of 37 PBMCs collected on the first day of leukapheresis had detectable HHV-8 (P = 0.016). HHV-8 was more frequently identified in autograft products before vs after Ceprate SC selection (40% vs 15%, P = 0.016). Although the role HHV-8 plays in myeloma pathogenesis remains unclear, these results imply that mobilization chemotherapy increases the numbers of circulating HHV-8-infected dendritic cells within the peripheral blood. In addition, CD34 selection of autograft products in MM patients may reduce the reintroduction of virally infected cells following high-dose chemotherapy. Bone Marrow Transplantation (2000) 25, 153-160.

Antigens, CD34↗