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Biomedical subjects

R Griffiths

Publications and source records attributed to R Griffiths.

At least 19 recordsLinked to original sources
PubMed2002

Sex-specific foraging behaviour in a monomorphic seabird.

Sexual differences in the foraging behaviour of parents have been observed in a number of sexually sizedimorphic birds, particularly seabirds, and the usual inference has been that these sex-specific differences are mediated primarily by differences in body size. To test this explanation, we compared the foraging behaviour of parents in a monomorphic seabird species, the northern gannet Morus bassanus. Using specially designed instruments and radio telemetry we found that individuals of both sexes were consistent in the directions and durations of their foraging trips. However, there were significant differences in the foraging behaviour of males and females. Female gannets were not only more selective than males in the areas where they foraged, but they also made longer, deeper dives and spent more time on the sea surface than males. As the sexes are morphologically similar in this species, then these differences are unlikely to have been mediated by body size. Our work highlights the need to investigate sexual differences in the foraging behaviour of seabirds and other species more closely, in order to test alternative theories that do not rely on differences in body size.

Animals↗
PubMed2001

Characterization of the 1H-cyclopentapyrimidine-2,4(1H,3H)-dione derivative (S)-CPW399 as a novel, potent, and subtype-selective AMPA receptor full agonist with partial desensitization properties.

(S)-CPW399 (2b) is a novel, potent, and subtype-selective AMPA receptor full agonist that, unlike (S)-willardiine and related compounds, in mouse cerebellar granule cells, stimulated an increase in [Ca(2+)](i), and induced neuronal cell death in a time- and concentration-dependent manner. Compound 2b appears to be a weakly desensitizing, full agonist at AMPA receptors and therefore represents a new pharmacological tool to investigate the role of AMPA receptors in excitotoxicity and their molecular mechanisms of desensitization.

Alanine↗
PubMed2001

Increased reproductive effort results in male-biased offspring sex ratio: an experimental study in a species with reversed sexual size dimorphism.

Adaptive sex-ratio theory predicts that parents should overproduce the more beneficial offspring sex. Based on a recent experimental study of lesser black-backed gulls, we tested this hypothesis with the great skua, Catharacta skua, a bird species closely related to gulls but where females are the larger sex. When in poor body condition, the gulls overproduced daughters, the smaller and more viable sex under those circumstances. To discriminate between a mandatory physiological overproduction of female (i.e. non-male) eggs versus the overproduction of the smaller and presumably more viable sex, we conducted an egg-removal experiment with the great skua. Since the males are smaller, larger size and being male are separated. Through egg removal we induced females to increase egg production effort. Eggs were sexed using a DNA-based technique. Manipulated pairs produced a significant male bias at the end of the extended laying sequence, while the sex ratio in the control group did not differ from unity. Our results present an example of facultative sex-ratio manipulation and support the hypothesis that in sexually dimorphic birds parents overproduce the smaller sex under adverse conditions.

Adaptation, Physiological↗
PubMed2001

The effect of treatment with Campath-1H in patients with autoimmune cytopenias.

We describe 21 patients with severe and life-threatening autoimmune cytopenias resistant to standard immunosuppression who were treated with the monoclonal antibody Campath-1H. Four patients had autoimmune neutropenia, four had autoimmune haemolytic anaemia, four had pure red cell aplasia, one had immune thrombocytopenia purpura (ITP), three had autoimmune haemolytic anaemia and ITP (Evan's syndrome), three had autoimmune pancytopenia (ITP, autoimmune neutropenia and autoimmune haemolytic anaemia), one had ITP (associated with acquired Glanzmann's disease) and autoimmune neutropenia, and one had ITP and red cell aplasia. Campath-1H was administered at a dose of 10 mg/d as an intravenous infusion for 10 d. Responses were seen in 15 patients, which were sustained in six. Relapse occurred in eight patients after Campath-1H treatment. Patients entering the study later, received cyclosporine after Campath-1H in an attempt to reduce the incidence of relapse. Three patients received a second course of Campath-1H; all responded but later relapsed. Fourteen patients are alive at a median of 12 months (range 4-61) after Campath-1H. Campath-1H represents an alternative therapeutic option for severe, refractory autoimmune cytopenias.

Adolescent↗
PubMed2001

Developing evidence-based clinicians.

Evidence-based care has heralded an advancement for health with extensive rhetoric and incentives encouraging clinicians to become active participants in practice change. This paper explores two mechanisms-research utilization and systematic reviews--as processes to develop empowerment in clinicians, and develop an ethos of basing practice on research. The intent of these approaches is to create an environment that enables clinicians to seek solutions to practice problems, inform practice decisions and develop practice policy using evidence from research. The goal is to develop evidence-based clinicians who remain active and interested in their practice and who are committed to promoting the application of research to practice. The strengths and weaknesses of these methods are explored within two case studies where they are applied to the management of hypothermia and the efficacy of postoperative observations. Key points of application for each of the methods are outlined in the conclusions.

Australia↗
PubMed2001

Identification and characterization of a novel class of interleukin-1 post-translational processing inhibitors.

Lipopolysaccharide (LPS)-activated monocytes and macrophages produce large quantities of pro-interleukin (IL)-1beta but externalize little mature cytokine. Efficient post-translational processing of the procytokine occurs in vitro when these cells encounter a secretion stimulus such as ATP, cytolytic T cells, or hypotonic stress. Each of these stimuli promotes rapid conversion of 31-kDa pro-IL-1beta to its mature 17-kDa species and release of the 17-kDa cytokine. In this study, two novel pharmacological agents, CP-424,174 and CP-412,245, are identified as potent inhibitors of stimulus-coupled IL-1beta post-translational processing. These agents, both diarylsulfonylureas, block formation of mature IL-1beta without increasing the amount of procytokine that is released extracellularly, and they inhibit independently of the secretion stimulus used. Conditioned medium derived from LPS-activated/ATP-treated human monocytes maintained in the absence and presence of CP-424,174 contained comparable quantities of IL-6, tumor necrosis factor-alpha (TNFalpha), and IL-1RA, but 30-fold less IL-1beta was generated in the test agent's presence. As a result of this decrease, monocyte conditioned medium prepared in the presence of CP-424,174 demonstrated a greatly diminished capacity to promote an IL-1-dependent response (induction of serum amyloid A synthesis by Hep3B cells). Oral administration of CP-424,174 to mice resulted in inhibition of IL-1 in the absence of an effect on IL-6 and TNFalpha. These novel agents, therefore, act as selective cytokine release inhibitors and define a new therapeutic approach for controlling IL-1 production in inflammatory diseases.

Adenosine Triphosphate↗
PubMed2000

A role for fractalkine and its receptor (CX3CR1) in cardiac allograft rejection.

The hallmark of acute allograft rejection is infiltration of the inflamed graft by circulating leukocytes. We studied the role of fractalkine (FKN) and its receptor, CX(3)CR1, in allograft rejection. FKN expression was negligible in nonrejecting cardiac isografts but was significantly enhanced in rejecting allografts. At early time points, FKN expression was particularly prominent on vascular tissues and endothelium. As rejection progressed, FKN expression was further increased, with prominent anti-FKN staining seen around vessels and on cardiac myocytes. To determine the capacity of FKN on endothelial cells to promote leukocyte adhesion, we performed adhesion assays with PBMC and monolayers of TNF-alpha-activated murine endothelial cells under low-shear conditions. Treatment with either anti-FKN or anti-CX(3)CR1-blocking Ab significantly inhibited PBMC binding, indicating that a large proportion of leukocyte binding to murine endothelium occurs via the FKN and CX(3)CR1 adhesion receptors. To determine the functional significance of FKN in rejection, we treated cardiac allograft recipients with daily injections of anti-CX(3)CR1 Ab. Treatment with the anti-CX(3)CR1 Ab significantly prolonged allograft survival from 7 +/- 1 to 49 +/- 30 days (p < 0.0008). These studies identify a critical role for FKN in the pathogenesis of acute rejection and suggest that FKN may be a useful therapeutic target in rejection.

Animals↗
PubMed2000

Possible role for the FosB/JunD AP-1 transcription factor complex in glutamate-mediated excitotoxicity in cultured cerebellar granule cells.

The potent excitatory and neurotoxic actions of glutamate are known to influence the expression of a variety of genes, including those encoding the AP-1 transcription factor, which comprises proteins belonging to the Fos and Jun families. However, the precise role of Fos- and Jun-like transcription factors in these events remains elusive. Here we demonstrate, using primary cultures of mouse brain cerebellar granule cells as an in vitro model system, a possible involvement of the FosB/JunD heterodimer in excitotoxicity. Granule cells were grown for either 2 or 7 days in vitro (DIV) before exposure to varying concentrations (1-3000 microM) of the excitotoxin glutamate. In 7-DIV cells, glutamate induced a concentration-dependent neuronal death, whereas, in 2-DIV cells, no glutamate-induced neuronal damage was seen. We were particularly interested in comparing the protein composition of the AP-1 transcription factor complex in cells exposed to excitotoxic and to nontoxic conditions. AP-1 DNA binding activity was demonstrated by gel shift analysis in nuclear extracts derived from 7-DIV cells following exposure to either a nontoxic (10 microM) or an excitotoxic (250 microM) dose of glutamate and was similarly observed in extracts of 2-DIV cells exposed to the same levels of glutamate. Gel supershift analysis using antibodies against the different Fos and Jun family members allowed differentiation between AP-1 DNA binding in nuclear extracts as a function of both 1) viability status and 2) the stage of development. Of major significance was the finding that FosB could be detected as a component of AP-1 in 7-DIV cells only under excitotoxic conditions, whereas c-Fos, Fra-2, and JunD proteins were detectable under both excitotoxic and nontoxic conditions in cells of this age. In 2-DIV cells (in which glutamate is nontoxic), AP-1 comprised combinations of only Fra-1, Fra-2, c-Jun, and JunD. Because Fos family members are unable to form homodimers, this finding raises the possibility that the FosB/JunD heterodimer may have special significance in the mechanism of excitotoxic neuronal death.

Animals↗
PubMed2000

Primary care groups. Serving from the shadows.

A study of appointments to the boards of 59 PCGs covered by the 13 health authorities in the West Midlands found concerns about fairness, openness and transparency. There was concern about the lack of a competency framework for GP members. Health authorities questioned whether the lay members of boards were representative of the local population. Some health authorities provided no induction training for boards.

Community Participation↗
PubMed2000

H2-DMalpha(-/-) mice show the importance of major histocompatibility complex-bound peptide in cardiac allograft rejection.

The role played by antigenic peptides bound to major histocompatibility complex (MHC) molecules is evaluated with H2-DMalpha(-/)- mice. These mice have predominantly class II-associated invariant chain peptide (CLIP)-, not antigenic peptide-bound, MHC class II. H2-DMalpha(-/)- donor heart grafts survived three times longer than wild-type grafts and slightly longer than I-A(beta)(b)-(/)- grafts. Proliferative T cell response was absent, and cytolytic response was reduced against the H2-DMalpha(-/)- grafts in vivo. Residual cytolytic T cell and antibody responses against intact MHC class I lead to eventual rejection. Removal of both H2-DMalpha and beta2-microglobulin (beta2m) in cardiac grafts lead to greater (8-10 times) graft survival, whereas removal of beta2m alone did not have any effect. These results demonstrate the significance of peptide rather than just allogeneic MHC, in eliciting graft rejection.

Animals↗
PubMed2000

Altered intragraft immune responses and improved renal function in MHC class II-deficient mouse kidney allografts.

BACKGROUND: During renal allograft rejection, expression of MHC class II antigens is up-regulated on the parenchymal cells of the kidney. This up-regulation of MHC class II proteins may stimulate the intragraft alloimmune response by promoting their recognition by recipient CD4+ T cells. In previous studies, absence of donor MHC class II antigens did not affect skin graft survival, but resulted in prolonged survival of cardiac allografts. METHODS: To further explore the role of MHC class II antigens in kidney graft rejection, we performed vascularized kidney transplants using donor kidneys from A(beta)b-deficient mice that lack MHC class II expression. RESULTS: At 4 weeks after transplant, GFR was substantially depressed in control allografts (2.18+/-0.46 ml/min/kg) compared to nonrejecting isografts (7.98+/-1.62 ml/min/kg; P<0.01), but significantly higher in class II- allografts (4.38+/-0.60 ml/min/kg; P<0.05). Despite the improvement in renal function, class II- allograft demonstrated histologic features of acute rejection, not unlike control allografts. However, morphometric analysis at 1 week after transplantation demonstrated significantly fewer CD4+ T cells infiltrating class II- allografts (12.8+/-1.2 cells/mm2) compared to controls (25.5+/-2.6 cells/mm2; P=0.0007). Finally, the intragraft profile of cytokines was altered in class II- allografts, with significantly reduced expression of Th2 cytokine mRNA compared to controls. CONCLUSIONS: These results support a role of MHC class II antigens in the kidney regulating immune cells within the graft. Further, effector pathways triggered by class II antigens promote renal injury during rejection.

Animals↗
PubMed2000

Perceived expressed emotion in the siblings and parents of hospitalized patients with anorexia nervosa.

OBJECTIVE: The present study investigated the relationship between the level of perceived Expressed Emotion (EE) of the siblings and parents of patients hospitalized with anorexia nervosa and its effect on weight gain and psychological functioning. METHOD: The Level of Expressed Emotion (LEE) Scale was administered on admission to 19 patients with anorexia nervosa who completed the LEE three times so as to identify their perceptions of their relationship with their closest age sibling, mother, and father. They were also required to complete the Eating Disorder Inventory 2 (EDI-2). Patients' closest age sibling completed the Family Attitude Scale (FAS). The patients' body mass index (BMI) was calculated 6 weeks later, and the EDI-2 readministered. RESULTS: Perceived EE was not predictive of BMI change after 6 weeks of hospitalization. A composite perceived family EE score was a significant predictor of change on the Interpersonal Distrust, Maturity Fears, and Perfectionism subscales of the EDI-2. DISCUSSION: These findings suggest that patients' perceptions of their relationships with their closest aged sibling, mother, and father are poor predictors of weight gain and improvement in psychological functioning following 6 weeks of inpatient treatment.

Adult↗
PubMed2000

Development of an instrument to assess readiness to recover in anorexia nervosa.

OBJECTIVE: The degree to which patients with anorexia nervosa demonstrate readiness to recover from their illness has received scant theoretical or empirical attention. Investigating the prevalence and degree of amotivation for recovery in anorexia nervosa, its role in outcome, and the effectiveness of interventions designed to enhance readiness to recover necessitates the existence of a reliable and valid measure of motivational issues relevant to the disorder. The present study aimed to develop and evaluate an instrument for assessing readiness to recover in anorexia nervosa, namely, the Anorexia Nervosa Stages of Change Questionnaire (ANSOCQ), a 23-item self-report questionnaire based on Prochaska and DiClemente's stages of change model. METHOD: Seventy-one inpatients with anorexia nervosa participated in the study. On several occasions during their admission, participants completed the ANSOCQ as well as questionnaires assessing readiness to recover, anorexic symptomatology, general distress, and social desirability. RESULTS: The ANSOCQ demonstrated good internal consistency (.90) and 1-week test-retest reliability (.89). Various aspects of validity were also supported, such as significant relationships with other instruments assessing readiness to recover and the prediction of weight gain during different periods of treatment. DISCUSSION: The results suggest that the ANSOCQ is a psychometrically sound instrument that may prove useful in investigating the role of readiness to recover in anorexia nervosa.

Adolescent↗
PubMed2000

General versus spinal/epidural anaesthesia for surgery for hip fractures in adults.

BACKGROUND: The majority of hip fracture patients are treated surgically, requiring anaesthesia. OBJECTIVES: To compare different types of anaesthesia for surgical repair of hip fractures (proximal femoral fractures) in adults. This is primarily regional (spinal or epidural) anaesthesia versus inhalation general anaesthesia, but also includes ketamine anaesthesia versus inhalation general anaesthesia. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group trials register, Medline, selected orthopaedic and anaesthetic journals and conference proceedings, and reference lists of relevant articles. Date of the most recent search: August 1998. SELECTION CRITERIA: Randomised and quasi-randomised trials comparing different methods of anaesthesia for hip fracture surgery in skeletally mature persons. Trials comparing the use of local nerve blocks are not considered in this review. Neither are trials using different types of drugs or techniques with one type of anaesthesia. The primary outcome was mortality. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality, using a nine item scale, and extracted data. The other two reviewers independently checked these results. Wherever appropriate and possible, results were pooled. MAIN RESULTS: Fifteen trials, involving 2162 patients, which compared regional anaesthesia with general anaesthesia, were included. All trials had methodological flaws. Regional anaesthesia was associated with a decreased mortality at one month (49/766 (6.4%) versus 76/812 (9.4%)) of borderline statistical significance (Peto odds ratio 0.66, 95% confidence interval 0.46 to 0.96)). The results for three month mortality were not statistically significant, although the confidence interval does not exclude the possibility of a clinically relevant reduction (86/726 (11.8%) versus 98/765 (12.8%), Peto odds ratio 0.91, 95% confidence interval 0.67 to 1.24). The reduced numbers at one year, coming exclusively from two studies, preclude any useful conclusions for long term mortality (80/354 (22.6%) versus 78/372 (21.0%), Peto odds ratio 1.10, 95% confidence interval 0.77 to 1.57). Regional anaesthesia was associated with a tendency to a longer operation (weighted mean difference 4.8 minutes, 95% confidence interval 1.1 to 8.6 minutes), and a reduced risk of deep venous thrombosis (39/129 (30%) versus 61/37(76%); Peto odds ratio 0. 41, 95% confidence interval 0.23 to 0.72), although this conclusion is insecure due to possible selection bias in the subgroups in whom this outcome was measured. No other statistically significant differences in outcome were identified. There was insufficient evidence to draw any conclusions from a further two included trials, involving a total of 100 patients, which compared other types of anaesthesia. REVIEWER'S CONCLUSIONS: Regional anaesthesia and general anaesthesia appear to produce comparable results for most of the outcomes studied. Regional anaesthesia may reduce short-term mortality but no conclusions can be drawn for longer term mortality.

Adult↗