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Biomedical subjects

M McGrath

Publications and source records attributed to M McGrath.

At least 37 records · Page 2Linked to original sources
PubMed1998

Rewards and gratifications among family caregivers: towards a refined model of caring and coping.

Supplemented by a case illustration, findings from a study in Wales are reported for the first time from the application of two new instruments for measuring rewards and stresses among family caregivers. The paper takes as its starting point a critique of models of caregiving which emphasize instrumental and pathological dimensions. Findings suggest that caregivers report the existence of pervasive rewards and gratifications, as well as stresses, as part of the caregiving experience, and that these stem from varying sources. The role of rewards and satisfactions in stress-coping models is briefly discussed, and implications for changed practice and policy thinking are reviewed.

Activities of Daily Living↗
PubMed1997

The KSHV/HHV8-infected BCBL-1 lymphoma line causes tumors in SCID mice but fails to transmit virus to a human peripheral blood mononuclear cell graft.

The body-cavity-based lymphoma cell line BCBL-1, which is infected with Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8, was injected alone or with human peripheral blood mononuclear cells into SCID mice. Immunoblastic lymphomas developed at or near the site of injection. The lymphomas appeared to derive exclusively from the injected BCBL-1 cells and not from the injected human PBMC. The tumors elicited a marked murine angiogenic response, but known angiogenic cytokines were not detected in BCBL-1 cells. Transfer of BCBL-1 cells to SCID mice may represent an in vivo model for the study of KSHV/HHV8-stimulated angiogenesis.

Animals↗
PubMed1996

Biological predictors of 1-year outcome in schizophrenia in males and females.

This paper describes a prospective study designed to ascertain the predictive value of biological factors associated with schizophrenia in males and females. In a sample of 59 medication-free schizophrenic inpatients (41 males; 18 females), we assessed the correlation of four factors--rapid eye movement (REM) sleep latency, delta (slow-wave) sleep, dexamethasone suppression test (DST) cortisol levels, and ventricle-brain ratio (VBR)--with several dimensions of outcome at 1-year post-discharge. In the total sample, shorter REM latency was associated with poor outcome on all dimensions measured: rehospitalization, employment, social activity, symptomatology, and global functioning. However, none of the other biological factors were associated with any measure of outcome. The predictive value of REM latency appeared to be gender-specific; in general, the relationships between reduced REM latency and poor outcome were consistently noted in females, but were not significant in males. These results suggest that a common, possibly gender-related, pathophysiological mechanism might underlie both abnormal REM latency and poor outcome. The findings underscore the importance of considering gender differences in studies of schizophrenia.

Electroencephalography↗
PubMed1996

Effects of dietary n-3 fatty acid supplementation in men with weight loss associated with the acquired immune deficiency syndrome: Relation to indices of cytokine production.

Cytokines may be involved in weight loss and disturbances of metabolism associated with human immunodeficiency virus (HIV) infection. Dietary n-3 fatty acids reduce the production of interleukin-1 (IL-1) and tumor necrosis factor (TNF) by peripheral blood mononuclear cells (PBMC) in normal humans and prevent IL-1 and TNF anorexia in animals. Accordingly, we studied the nutritional and metabolic effects of a 10-week trial of dietary fish oil (MaxEPA 18 g/day) in men with weight loss due to acquired immune deficiency syndrome (AIDS). Twenty men were enrolled, and 16 completed the 10-week supplementation period. Prior weight loss was 13.7 +/- 1.8 kg(17.4 +/- 1.6% body weight, means +/- SE). Food intake, body composition, blood chemistries, serum cytokine concentrations, in vitro production of IL-1 and TNF by PBMC, and clinical course were followed. A subset of subjects (n=12) underwent stable isotope infusions to measure de novo hepatic lipogenesis (DNL), an in vivo metabolic index that is influenced by cytokine presence and has previously been found to be elevated in AIDS. An unsupplemented group of men with AIDS wasting (10.4 +/- 2.4 kg weight loss, 13.1 +/- 2.2% body weight) was monitored for 10 weeks as controls. Baseline food intake (2,395 +/- 177 kcal/day and 95.1 +/- 7.2 g protein/day), body weight, percent fat, and fat-free mass were unchanged over the 10-week supplementation period. Serum triglycerides were reduced in hypertriglyceridemic subjects, confirming compliance with fish oil supplementation and suggesting that their hypertriglyceridemia was at least in part due to overproduction. Serum TNF and IL-1 were undetectable before or after fish oil supplementation. Serum interferon alpha (IFN) was measurable but did not change. In vitro production of IL-1 and TNF by PBMC was markedly reduced both at baseline and after fish oil supplementation in this population, even in the presence of new AIDS complications, compared with normal controls. The metabolic measurement DNL fell and weight was gained (2.1 +/- 1.3 kg) in subjects who did not develop new AIDS-related complications, but further increases in DNL and further weight loss were observed in subjects who developed a new AIDS complication (p<0.05 for interaction between new complication and change in DNL). No changes in body weight, food intake, serum triglycerides, serum cytokines, or DNL were observed in the unsupplemented group. We conclude that fish oil is a weak anticytokine agent that is unable to overcome the metabolic and nutritional consequences of acute AIDS-related complications but may exert a clinical anticytokine effect in stable AIDS patients. Cytokine production by PBMC is not a useful or reliable marker of in vivo cytokine activity in AIDS patients with weight loss. In contrast, an integrative functional index that is sensitive to cytokine presence in tissues (hepatic DNL) correlated with clinical response. These findings are relevant to the design of future studies of more potent anticytokine agents, such as thalidomide.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Lytic growth of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in culture.

Kaposi's sarcoma (KS) is the leading neoplasm of AIDS patients, and HIV infection is known to be a major risk factor for its development. However, KS can occur in the absence of HIV infection and the risk of KS development varies widely even among HIV-infected patients, with homosexual men with AIDS being 20 times more likely to develop KS than AIDS-afflicted children or hemophiliacs. These and other data strongly suggest that a sexually transmitted agent or co-factor may be involved in KS pathogenesis. Recently, DNA sequences corresponding to the genome of a novel member of the herpesvirus family have been identified within AIDS-KS biopsies, and several reports indicate that these sequences are also present in all forms of HIV-negative KS. These and other findings suggest this new agent, referred to as KS-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV8), as a candidate for the putative etiologic cofactor. However, the role of this agent in KS remains hotly debated. Further progress in understanding its biology has been severely hampered by the lack of a cell culture system for virus growth. Here we report the development of a system for the lytic growth of this virus in a latently infected B cell line and present the first ultrastructural visualization of the virus. This system will facilitate the detailed study of the molecular biology of viral replication, the testing of antiviral drugs and the development of diagnostic tests for viral infection.

Acquired Immunodeficiency Syndrome↗
PubMed1996

IL-1 beta production by human polymorphonuclear leucocytes stimulated by anti-neutrophil cytoplasmic autoantibodies: relevance to systemic vasculitis.

Neutrophils accumulate in the acute blood vessel lesions of patients with autoimmune systemic vasculitis. They have been shown previously to produce the cytokine IL-1 beta in response to stimulation with TNF. This study demonstrates that neutrophils can be stimulated by anti-neutrophil cytoplasmic antibodies (ANCA), which are present in patients with systemic vasculitis, to express mRNA and protein for IL-1 beta. Both human ANCA and MoAbs to a variety of autoantigens recognized by ANCA, including proteinase 3, myeloperoxidase, bactericidal/permeability increasing protein and elastase, are effective. This response can be inhibited by actinomycin and cycloheximide, suggesting a requirement for de novo protein synthesis. IL-1 beta production can be inhibited by pooled human intravenous immunoglobulins but not by FK506 or cyclosporin A. These data suggest that ANCA in patients with active vasculitis may stimulate neutrophils to produce cytokines. It is hypothesized that cytokine production from neutrophils that accumulate in significant numbers in vasculitic lesions contribute to and augment the local inflammatory response by the activation of vascular endothelial cells and infiltrating leucocytes.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1996

Family stress and metabolic control in diabetes.

The common clinical assumption that stress has a deleterious effect on metabolic control in insulin dependent diabetes mellitus (IDDM) has not been confirmed in children and adolescents. This cross sectional study of 43 children and adolescents with IDDM and their families examined the relations between family life stress, family social support, and metabolic control. High family life stress was found to be strongly correlated with HbA1c in the whole group (n = 43) and in children under 12 years (n = 27) when considered separately. Family social support was not found to be directly related to HbA1c, but was found to buffer the effects of family life stress. These findings support the hypotheses that family stress affects metabolic control in IDDM and that good social support buffers these deleterious effects.

Adolescent↗
PubMed1995

Role of the cytoskeleton in the reaction of fibroblasts to multiple grooved substrata.

The role of the cytoskeleton and cell attachments in the alignment of baby hamster kidney fibroblasts to ridge and groove substratum topography was investigated using confocal scanning microscopy. This was carried out with normal cells and cells treated with the cytoskeleton modifiers cytochalasin D, colcemid, and taxol. Actin was localised with fluorescent phalloidin. Tubulin, vinculin, and intracellular adhesion molecule-1 were visualised by indirect immunofluorescence. The spreading, elongation, and orientation of the cells after 24 h of culture in these conditions were measured on grooves of 5, 10, and 25 microns width and 0.5, 1, 2, and 5 microns depth. We have also observed events over the first 30 min of cell attachment. Five minutes after cell attachment, F-actin condensations were seen close to the intersection of groove wall and ridge top, that is, at a topographic discontinuity. The condensations were often at right angles to the groove edge and showed a periodicity of 0.6 microns. Vinculin arrangement at the early stages of cell spreading was similar to that of actin. Organisation of the microtubule system followed later, becoming obvious at about 30 min after cell plating. The Curtis and Clark theory (that cells react to topography primarily at lines of discontinuity in the substratum by actin nucleation) is supported by these results. The use of cytoskeletal poisons did not entirely abolish cell reaction to grooves. Colcemid increased cell spreading and reduced cell orientation and elongation. Cytochalasin D reduced cell spreading, orientation, and elongation. Taxol reduced cell elongation but did not affect cell spreading and orientation. We conclude that the aggregation of actin along groove/ridge boundaries is a primary driving event in determining fibroblast orientation on microgrooved substrata.

Animals↗
PubMed1995

Mastery motivation and cognitive development in 4-year-old children born at various degrees of medical risk.

Although technology has enabled premature infants to survive, longitudinal assessments have primarily focused on IQ outcomes. The purpose of this study was to establish the usefulness of mastery assessment in establishing developmental outcome. Mastery motivation and cognition were examined in 167 preschool children born at various degrees of medical risk. Mastery motivation was measured by a videotaped toy sequence designed to tap sensorimotor practice, effect production, and problem solving. Patterns of correlations indicate that the relationship between mastery and IQ were complementary and not redundant. Three regression models showed that significant interactions between perinatal status and mastery motivation behaviors confirm mastery assessment worthy of consideration in biologically high-risk children.

Achievement↗
PubMed1995

Early clinical experience with a hybrid bioartificial liver.

BACKGROUND: Severe liver failure is associated with high mortality. Orthotopic liver transplantation (OLT) is the only effective therapeutic modality; there is a need for a 'bridge' system to support patients until an organ becomes available. METHODS: A bioartificial liver (BAL) was used to treat 10 patients with severe liver failure. A plasmapheresis system was used to pump patient plasma through a module with porcine hepatocytes. Each treatment lasted 6-7 h. RESULTS: All patients tolerated the procedure(s) well. Eight patients underwent OLT following BAL treatment(s). There were two late deaths after recovery from liver failure. Five patients with increased intracranial pressure (ICP) and decerebration had ICP normalization, increased cerebral perfusion pressure and full neurologic recovery after OLT. There was improvement in the level of encephalopathy and a significant decrease in serum ammonia after BAL treatment(s). CONCLUSIONS: BAL treatment is safe and beneficial and can be successfully used as a 'bridge' to transplantation.

Adult↗
PubMed1994

A bioartificial liver to treat severe acute liver failure.

OBJECTIVE: To test the safety and efficacy of a bioartificial liver support system in patients with severe acute liver failure. SUMMARY BACKGROUND DATA: The authors developed a bioartificial liver using porcine hepatocytes. The system was tested in vitro and shown to have differentiated liver functions (cytochrome P450 activity, synthesis of liver-specific proteins, bilirubin synthesis, and conjugation). When tested in vivo in experimental animals with liver failure, it gave substantial metabolic and hemodynamic support. METHODS: Seven patients with severe acute liver failure received a double lumen catheter in the saphenous vein; blood was removed, plasma was separated and perfused through a cartridge containing 4 to 6 x 10(9) porcine hepatocytes, and plasma and blood cells were reconstituted and reinfused. Each treatment lasted 6 to 7 hours. RESULTS: All patients tolerated the procedure(s) well, with neurologic improvement, decreased intracranial pressure (23.0 +/- 2.3 to 7.8 +/- 1.7 mm Hg; p < 0.005) associated with an increase in cerebral perfusion pressure, decreased plasma ammonia (163.3 +/- 21.3 to 112.2 +/- 9.8 microMoles/L; p < 0.01), and increased encephalopathy index (0.60 +/- 0.17 to 1.24 +/- 0.22; p < 0.03). All patients survived, had a liver transplant, and were discharged from the hospital. CONCLUSIONS: This bioartificial liver is safe and serves as an effective "bridge" to liver transplant in some patients.

Adolescent↗
PubMed1993

Breaking the adhesions of a cell with its substratum.

Investigation of the relative slowness with which trypsin detaches epithelial cells from their adhesions with a substratum suggests that the adherent surface of the cells is normally rather inaccessible to the enzyme. Trypsinisation of cells through a porous filter allowing access of the enzyme to the underside of the cells greatly accelerated detachment: a result consistent with this explanation.

Animals↗
PubMed1993

A non-lymphoma idiotype is indicative and predictive for B cell malignancies in AIDS.

The 1F7 idiotype previously defined (J Immunol 147:933;1991 and Eur J Immunol 22:1749;1992) is expressed on antibodies reactive to different proteins of HIV (gp41, p24, gp120). Since serum levels of 1F7 (IgM or IgG) are significantly higher in patients with HIV lymphoma as opposed to HIV-infected individuals, normal controls and non-HIV lymphoma patients, we hypothesized the B-cell neoplasms were the source of the idiotype. However, immunohistochemistry on cryostat sections revealed no 1F7 idiotype signal on neoplastic B-cells nor tumor infiltrative T-cells (n = 8). Interestingly, reactive lymphocytosis adjacent to tumor masses and reactive follicular hyperplastic controls (n = 5) exhibited significant 1F7 reactivity. The reactivity appeared in paracortical and perifollicular lymphoid regions, predominantly regions of B, T and antigen presenting cells in lymph nodes or tonsils. A survey of electrophoretically defined paraproteins with anti-HIV specificities derived from HIV-infected patients showed no Western blot reactivity with the 1F7 anti-idiotypic antibody. Therefore, the idiotype does not appear to be a direct product of B-cell neoplasia or abnormal B-cell proliferation, but is produced by B cell clones responding to HIV infection. This high level of serum 1F7 reactivity could be an important clue in the pathogenesis of HIV lymphomas and confers a highly predictive serological test for HIV lymphoma.

Animals↗
PubMed1993

Nailfold capillary circulation in osteoarthritis.

Nailfold capillaries in 28 patients with OA affecting the distal interphalangeal joints were compared to 23 age- and sex-matched controls without OA. Patients with OA showed a significantly lower density of capillaries in their nailfolds and significantly more capillary morphological abnormalities including haemorrhage, 'drop out', dilatation and irregularity. There was a trend for OA patients to have warmer fingers with reduced finger to brachial blood pressure ratios. There were significant correlations between nailfold capillary numbers and average joint tenderness and between capillary morphological changes and joint swelling. These results reveal a relationship between interphalangeal joint OA and nailfold capillary abnormalities and density. As changes in microcirculation may be pertinent to the pathogenesis of OA, further studies which could explore possible causal relationships are warranted.

Aged↗