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Biomedical subjects

Diana Wood

Publications and source records attributed to Diana Wood.

5 recordsLinked to original sources
PubMed2003

The health-related quality-of-life impact of histamine dihydrochloride plus interleukin-2 compared with interleukin-2 alone in patients with metastatic melanoma.

The aim of this study was to compare the quality-of-life (QOL) effects of interleukin-2 (IL-2) alone with those of IL-2 plus histamine dihydrochloride in the setting of a multicenter, randomized trial for patients with metastatic melanoma. QOL data were collected from July 1997 to March 2000 during a phase III trial comparing subcutaneous histamine plus IL-2 and IL-2 alone. Prior to each treatment cycle, patients completed the 76-item Quality-of-Well-Being Scale-Self-Administered (QWB-SA) questionnaire, the Overall State of Health (OSH) item, and the General Health Perception (GHP) item. A longitudinal data analysis using the generalized estimating equations approach was performed to compare changes in QWB-SA scores over time between treatment groups, and predicted QWB-SA scores from the regression analysis were used to calculate quality-adjusted survival duration over the 12-month study period. QOL analyses were conducted for all randomized patients (intent-to-treat overall population, ITT-OA) and all patients who had liver metastases at randomization (ITT-LM population). In the ITT-OA population, differences in QWB-SA scores over time between the histamine plus IL-2 group (150 patients) and the IL-2 alone group (151 patients) were not significant (P=0.511, type III F test). In the ITT-LM population (53 histamine plus IL-2 patients and 73 IL-2 alone patients), changes in QWB-SA scores over time favored the histamine plus IL-2 group (P=0.018, type III F-test). In both the ITT-OA and ITT-LM populations, QWB-SA scores deteriorated more quickly over time in the IL-2 alone group than in the histamine plus IL-2 group, resulting in a significant difference in median quality-adjusted survival duration in favor of the histamine plus IL-2 group by 31.3 days in the ITT-OA population (P=0.007, Mann-Whitney U-test), and 50.2 days in the ITT-LM population (P=0.011). OSH and GHP scores did not differ between groups. The addition of subcutaneous histamine dihydrochloride to IL-2 treatment improved median quality-adjusted survival duration and did not adversely affect QOL in patients with malignant melanoma.

Adult↗
PubMed2002

Results from a randomized phase III study comparing combined treatment with histamine dihydrochloride plus interleukin-2 versus interleukin-2 alone in patients with metastatic melanoma.

PURPOSE: Reactive oxidative species (ROS) produced by phagocytic cells have been ascribed a role in the localized suppression of lymphocyte function within malignant tumors. Histamine has been shown to inhibit ROS formation and possibly synergize with cytokines to permit activation of natural killer cells and T cells. This study was designed to determine whether the addition of histamine to a subcutaneous (SC) regimen of interleukin-2 (IL-2) would improve the survival of metastatic melanoma patients. PATIENTS AND METHODS: A phase III, multicenter, randomized, parallel group study comparing IL-2 plus histamine with IL-2 alone was conducted in 305 patients with advanced metastatic melanoma. Patients were randomized to IL-2 (9 MIU/m(2) bid SC on days 1 to 2 of weeks 1 and 3, and 2 MIU/m(2) bid SC on days 1 to 5 of weeks 2 and 4) with or without histamine (1.0 mg bid SC days 1 to 5, weeks 1 to 4). The primary end point, survival, was prospectively applied to all randomized patients (intent-to-treat-overall population, ITT-OA) and all patients having liver metastases at randomization (ITT-LM population). Secondary end points included safety of the combined treatment, time to disease progression, and response rate. RESULTS: Combined treatment with histamine plus IL-2 significantly improved overall survival in the ITT-LM population (P =.004) and showed a trend for improved survival in the ITT population (P =.125). Grade 3 and 4 adverse events were comparable in the two arms. CONCLUSION: Use of histamine as an adjunct to IL-2 is safe, well tolerated, and associated with a statistically significant prolongation of survival compared with IL-2 alone in metastatic melanoma patients with liver involvement. Further trials to confirm and understand the role of histamine in this combination treatment are underway.

Adult↗
PubMed2002

Support for students with academic difficulties.

CONTEXT: The human and financial costs of academic failure amongst medical students are extremely high. Often, remedial support is infrequently available or is available only for students failing their final examinations. We describe the design, implementation and preliminary evaluation of a remedial programme (RP) for students who experience academic difficulties. METHODS: A total of 24 students were identified from Years 4 and 5 of the undergraduate medical course at our medical school. Students invited to participate were identified following failure in summative and/or continuous assessment processes. Students underwent an individual educational diagnosis by means of free discussion and a semi-structured interview. Each negotiated a problem list, action plan and learning contract with course tutors. Of the 24 students, 16 received academic support and tutorials. Tutorial content was determined by individual students and took place over a 6-12-month period, initially individually and subsequently in pairs. Regular feedback and appraisal occurred. Information was delivered to the medical school academic progress review system. Student satisfaction was investigated and subsequent examination scores reviewed. RESULTS: The causes of academic failure were widespread and ranged from deficient study skills to financial, domestic and emotional problems. In contrast, the subjects in which students had difficulty were remarkably similar, in that they all related to core clinical skills and frequently involved communication skills. Students enjoyed the programme, reported improved motivation both for study and for their chosen career and demonstrated a greatly improved pass rate in subsequent examinations. CONCLUSIONS: The causes of academic failure in undergraduate medical students are diverse and are often not academic in origin. Students can benefit from an individually tailored remedial programme and go on to success in subsequent parts of the curriculum. Provision of individually tailored remedial teaching is labour-intensive and requires full faculty support.

Curriculum↗
PubMed2002

Characterisation of the effects of potassium channel modulating agents on mouse intestinal smooth muscle.

The actions of agents which modulate ATP-sensitive potassium (K(ATP)) channels in excitable cells were investigated in an in-vitro preparation of mouse ileum from which the mucosa was removed. A range of potassium channel openers of diverse structure, cromakalim (0.1-100 microM), pinacidil (0.1-200 microM) and its analogue P1060 (0.1-200 microM), SDZ PCO400 ((-)-(3S,4R)-3,4-dihydro-3-hydroxy-2,2-dimethyl-4-(3-oxo-cyclopent-1-enyloxy)-2H-1-benzopyran-6-carbonitrile) (0.3-60 microM), caused concentration-related reduction in twitch height of electrical field stimulated ileum. P1060 and SDZ PCO400 were the most potent agents; diazoxide (0.1-100 microM) was without effect. The order of inhibitory potency, based on EC50 values (concentration of a relaxant producing 50% of the maximum inhibition of twitch) was: P1060 = SDZ PCO400 > cromakalim > pinacidil. The relaxant effect of the potassium channel openers was antagonised by the sulfonylureas glibenclamide (0.1-1.0 microM) and glipizide (3-30 microM) but the nature of the antagonism differed. Antagonism of P1060 and SDZ PCO400 by glibenclamide appeared to be competitive whereas the antagonism of relaxation induced by cromakalim and pinacidil was apparently not competitive. Both phentolamine (1-10 microM) and tolbutamide (100-300 microM) showed competitive antagonism of the actions of pinacidil while yohimbine (1-20 microM) did not antagonise relaxation and appeared to have actions at sites other than the K(ATP) channel in this preparation. The relative effectiveness of the antagonists on pinacidil-induced relaxation was found to be: glibenclamide > phentolamine > tolbutamide > yohimbine, which is in agreement with studies in other tissues. The results show that many structurally diverse potassium channel openers are potent relaxants of mouse ileum. These observations are consistent with the existence of ATP-dependent K+ channels in murine intestinal muscle which, however, differ somewhat in properties from those reported for vascular muscle and pancreatic beta-cells.

Animals↗