Biomedical subjects
Publications and source records attributed to R Griffiths.
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.
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.
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.
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.
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.
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.
BACKGROUND: Various nerve blocks using local anaesthetic agents have been used in order to reduce pain after hip fracture. OBJECTIVES: To determine the effects of nerve blocks (inserted either pre-operatively, operatively or post-operatively) as part of the treatment for a hip fracture. SEARCH STRATEGY: The Cochrane Musculoskeletal Injuries Group trials register, MEDLINE, and bibliographies of trial reports were searched. Date of the most recent search: April 1998. SELECTION CRITERIA: Randomised and quasi-randomised trials involving the use of nerve blocks as part of the care of a hip fracture patient. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality, by use of an eight item scale, and extracted data. Wherever appropriate, results of outcome measures were pooled. MAIN RESULTS: Six randomised or quasi-randomised trials involving 229 patients were included. One trial related to insertion of a nerve block pre-operatively and the remaining five, to peri-operative insertion. Nerve blocks resulted in a reduction of the quantity of parental or oral analgesia administered to control pain from the fracture/operation or during surgery. It was not possible to demonstrate if this reduction in analgesia use was associated with any clinical benefit. REVIEWER'S CONCLUSIONS: Because of the small number of patients included in this review and the differing type of nerve blocks and timing of insertion, it is not possible to determine if nerve blocks confer any benefit when compared with other analgesic methods as part of the treatment of a hip fracture. Further trials with larger numbers of patients and full reporting of clinical outcomes would be justified.
Using primary cultures of mouse cerebellar granule cells as an in vitro model system, it has been demonstrated that different profiles of temporal expression of the c-fos proto-oncogene are observed under non-excitotoxic and excitotoxic conditions. A ratio has been derived previously for the steady-state level of c-fos mRNA after 30 min and 240 min which suggests that a 240 min/30 min ratio of greater than 1 correlates with excitotoxicity, whereas a ratio of less than 1 correlates with a non-excitotoxic outcome. Moreover, a positive correlation is seen with abrogation of excitotoxicity in response to selective excitatory amino acid receptor antagonists. This test, proposed as a specific biomarker for excitotoxicity is undergoing prevalidation. Excitotoxicity is defined as neuronal cell death mediated by hyperactivation of glutamate receptor subtypes and therefore might be expected to be prevented by selective glutamate receptor antagonists. In preliminary evaluation studies, we have conducted work under the direction of the European Center for Validation of Alternate Methods (ECVAM) using compounds specified by ECVAM that have been subdivided into four groups based on known or presumed actions. These groups comprise: Group 1-endogenous/synthetic excitotoxins; Group 2-environmental, putative excitotoxins; Group 3-neurotoxic but non-excitotoxic compounds, and Group 4-non-toxic compounds. The results of this study support the proposal that the c-fos mRNA time-ratio test is a specific biomarker of excitotoxicity. Just as importantly, this test has the potential for application in screening newly-designed EAA receptor antagonists in the search for clinically relevant drugs to treat a variety of neuropathologies.
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A recent study in our department demonstrated that depressing the plunger of a 50-mL syringe was reliably and linearly related to the force applied between 20 N and 50 N. Using a 50-mL syringe we constructed a simple device to help train anaesthetic assistants to apply cricoid pressure correctly. We then tested anaesthetists, operating department practitioners (non-physicians) and nurses in our hospital to see if they could correctly apply forces of 20 and 40 N. All subjects were then trained using this apparatus and once confident were retested immediately afterwards, and again 1 week and 1 month later. The results show a wide variation in the force applied with only 30% of subjects applying appropriate force at 20 N, and 40% at 40 N. Training leads to a significant improvement in performance (P < 0.005 at 20 N and P < 0.001 at 40 N) which is maintained for 1 week for both 20 N (P < 0.05) and 40 N (P < 0.05) but not for 1 month. Therefore training should be practised on a weekly basis. This is an inexpensive and simple device that we believe to be useful in helping anaesthetic assistants to apply effective cricoid pressure.
BACKGROUND: Nephrotoxicity associated with cyclosporine A (CsA) administration is characterized by marked renal vasoconstriction, interstitial fibrosis, and arteriolar hypertrophy. While the molecular mechanisms of CsA toxicity are not well characterized, previous studies have demonstrated that altered arachidonic acid (AA) metabolism plays a role its pathogenesis. Using a rat renal transplant model, the purpose of this study was to examine the effects of CsA on the 5-lipoxygenase (5-LO) pathway of AA metabolism. METHODS: The PVG (RT1c) strain of rats underwent kidney transplantation, and recipients of nonrejecting kidney transplants were treated with either 50 mg/kg/day CsA or vehicle (N = 24). To determine the physiologic significance of increased leukotriene (LT) production, the peptidoleukotriene receptor antagonist SKF 106203 was administered to CsA-treated animals for six days. RESULTS: CsA caused a substantial reduction in glomerular filtration rate (GFR) in the transplanted rats compared with the vehicle-treated controls (1.5 +/- 0.6 vs. 4.1 +/- 0.8 mL/min/kg, P < 0.05). The reduction in renal function was associated with enhanced urinary excretion of the peptidoleukotriene metabolites LTE4 (1431 +/- 207 vs. 953 +/- 125 pg/24 h, P < 0.05) and N-acetyl-LTE4 (4411 +/- 848 vs. 463 +/- 70 pg/24 h, P < 0.001). LT receptor blockade had a significant protective effect on renal transplant function in CsA-treated animals (GFR, 4.8 +/- 1.1 vs. 1.7 +/- 0.9 mL/min/kg, P < 0.05), such that CsA-treated animals that received SKF106203 maintained GFR at levels similar to controls that never received CsA (4.1 +/- 0.8 mL/min/kg). Peptidoleukotriene receptor blockade also prevented the histomorphological abnormalities caused by CsA, including tubular vacuolization. CONCLUSIONS: These studies identify a critical role for LTs in the pathophysiology of CsA nephrotoxicity and suggest that LT antagonists may be useful in preventing CsA-associated kidney toxicity.
Hip fracture surgery is common and the population at risk is generally elderly. There is no consensus of opinion regarding the safest form of anaesthesia for these patients. We performed a meta-analysis of 15 randomized trials that compare morbidity and mortality associated with general or regional anaesthesia for hip fracture patients. There was a reduced 1-month mortality and incidence of deep vein thrombosis in the regional anaesthesia group. Operations performed under general anaesthesia had a reduction in operation time. No other outcome measures reached a statistically significant difference. There was a tendency towards a lower incidence of myocardial infarction, confusion and postoperative hypoxia in the regional anaesthetic group, and cerebrovascular accident and intra-operative hypotension in the general anaesthetic group. We conclude that there are marginal advantages for regional anaesthesia compared to general anaesthesia for hip fracture patients in terms of early mortality and risk of deep vein thrombosis.
OBJECTIVE: To develop a client-generated outcome measure for use in community nursing. METHOD: Participants for the study were identified from the case load of community health nurses, from a nursing home service and from residents of a retirement village. All participants had a diagnosis of venous leg ulcer (VLU) and/or type 2 diabetes. Preliminary development of the measure involved focus groups of community clients and health professionals, and pilot testing of an existing quality of life (QoL) measure, the Patient-Generated Index. The resulting Client-Generated Index was tested for reliability and validity. RESULTS: The Pearson's correlation coefficient between administration of the CGI at T1 and T2 was 0.526 (n = 51; p = 0.0001). The CGI correlated significantly with four of eight dimensions of the SF-36, and with pain as a clinical marker for VLU r = 0.54 (p = 0.001). Overall, participants with VLU reported a lower QoL (mean CGI score 2.8) compared to those with diabetes (mean CGI score 4.1). CONCLUSIONS: The CGI was developed to measure outcomes in community health settings. Some measures of its reliability and validity are demonstrated and further research is needed to validate the instrument using other client groups. IMPLICATIONS: If routine assessment and evaluation is to contribute to measures of outcome, the instruments need to be concise and acceptable to health care providers. The CGI has all these properties.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
We continue to explore the basics of anaesthesia with another article from Rachelle Griffiths, this month looking at supportive pharmacology. If you think this looks too complicated for a Back to Basics piece, read it in small chunks--and be grateful that you are not my spelling checker, which has gone berserk! This Back to Basics series is drawing to a close soon. However, if you have suggestions for any more articles, or perhaps an article itself, then do contact me via Headquarters.