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Biomedical subjects

A Dorward

Publications and source records attributed to A Dorward.

9 recordsLinked to original sources

Changes in patterns of acute medical receiving in Scotland 1996 to 2001.

The purpose of this study was to review changes in working practises of physicians and hospitals from 1996 to 2001 in the light of rising medical admissions and published reports into the organisation of acute admissions. Information was gathered by direct discussion with the appropriate lead doctor for each hospitals acute service in February 2001. The results were compared with a previously published study, which recorded the situation as of October 1996. The hospitals which were studied were the twenty seven Scottish hospitals which admit more than 3000 acute medical patients each year. There has been a 25% increase in number of consultants carrying out receiving duties. Nearly all hospitals now have an acute admission unit. Four hospitals have appointed acute care physicians. Triage of appropriate patients to more specialised ward based care has increased. There has been a rise in geriatricians involvement in acute receiving from four to fifteen hospitals. New developments include early discharge for chronic obstructive airway disease, outpatient management of venous thrombosis, discharge planning and streamlining investigation of chest pain. Two hospitals have specific alcohol support services. There continues to be progress and changes within medical and geriatric services over the last five years stimulated by the continuing rise in number of medical admissions.

Adult↗

Mitochondrial contributions to cancer cell physiology: redox balance, cell cycle, and drug resistance.

Alterations in the biochemistry of mitochondria have been associated with cell transformation and the acquisition of drug resistance to certain chemotherapeutic agents, suggesting that mitochondria may play a supportive role for the cancer cell phenotype. Mitochondria are multifunctional organelles that contribute to the cellular adenosine triphosphate (ATP) pool and cellular redox balance through the production of reactive oxygen intermediates (ROI). Our laboratory has focused on these mitochondrial functions in the context of cancer cell physiology to evaluate the potential role of mitochondria as controllers of tumour cell proliferation. Low concentrations of ROI have been implicated as messengers in intracellular signal transduction mechanisms; thus an imbalance of ROI production from the mitochondria may support cancer cell growth. In addition, suppression of mitochondrial ATP production can halt cell cycle progression at two energetic checkpoints, suggesting that the use of tumor-selective agents to reduce ATP production may offer a therapeutic target for cancer growth control.

Antineoplastic Agents↗

Coping with the inexorable rise in medical admissions: evaluating a radical reorganisation of acute medical care in a Scottish district general hospital.

OBJECTIVE: To describe radical changes in acute medical care in a district general hospital and assess their impact on staff and patients. DESIGN: A before and after comparison of structure, process and outcome indicators in the year preceding and following reorganisation. SETTING: The Adult Medicine Clinical Directorate of the Royal Alexandra Hospital in Paisley, Scotland. SUBJECTS: Staff in the Medical Directorate and a random sample of 400 patients. INTERVENTIONS: The main stimulus for reorganisation was the pressure caused by a relatively steep rise in admissions. In response, the six existing general medical wards were converted into a 38-bed Medical Admissions Unit and five more specialised wards. A new acute receiving rota allowed each consultant to concentrate almost exclusively on acute receiving for one week at a time. RESULTS: The boarding of patients in non-medical wards was eliminated through improved bed management. The needs of patients became better matched to the specialism of their consultant. The cardiologist's share of in-patients with cardiological problems rose from 34% of 2,877 cases to 58% of 3,085 cases (p < 0.001) and the respiratory physicians' share of respiratory in-patients grew from 53% of 1,281 cases to 67% of 1,287 cases (p < 0.001). After the reorganisation, medical staff had significantly fewer concerns about losing track of patients (p < 0.01) or about boarding (p < 0.01), however, concern about 'blocked beds' became greater (p < 0.05). Nurses reported more time for health promotion (p < 0.01) but also a rise in stress (p < 0.05). More patients reported that staff had time to explain their treatment (85/109 (79%) before, 93/105 (89%) after, p < 0.05) and a higher proportion felt ready for discharge (91/108 (84%) before, 99/106 (93%) after, p < 0.05). CONCLUSIONS: Radical reorganisation of medical care in response to rising acute medical admissions is achievable and may lead to improvements in care.

Adult↗

Activity of erythrocyte delta-aminolevulinic acid dehydratase in the female cynomolgus monkey (Macaca fascicularis): kinetic analysis in control and lead-exposed animals.

Kinetic analysis of erythrocyte delta-aminolevulinic acid dehydrase (delta-ALAD) from female cynomolgus monkeys revealed differences in pH optimum and Michaelis constants according to their exposure to lead. In vitro incubation of delta-ALAD with 5 mM dithiothreitol (DTT) or 100-200 microM zinc resulted in an enhanced enzyme activity being expressed. These effects were additive. Activation with DTT or zinc resulted in the abolition of pH differences between control and exposed animals and revealed an increased quantity of enzyme in exposed animals. delta-ALAD in control monkeys was observed to be very sensitive to inhibition by lead in vitro with an apparent inhibition constant (Ki) of 0.12 microM. The effect of lead on monkey delta-ALAD enzyme kinetics is similar to that seen with human samples and thus is a useful model for measuring biological response to lead exposure.

Animals↗

Phase II studies of mitozolomide in melanoma, lung and ovarian cancer.

Seventy-seven patients were treated with oral mitozolomide to assess the activity of this drug in melanoma, lung and ovarian cancer. Partial responses were seen in five of 18 evaluable patients with small cell lung cancer (SCLC) and three of 20 with melanoma. No activity was apparent in non small cell lung or epithelial ovarian cancer. The major toxicity was myelosuppression which necessitated reduction in the initial dosage from 115 to 90 mg/m2. However, even at this dose level, unpredictable WHO grade 4 toxicity occurred in non-pretreated patients. Thrombocytopenia was more common than leucopenia and eight patients required platelet transfusion for spontaneous or tumour-related haemorrhage. Myelotoxicity was considered responsible for two deaths and was a significant contributory factor in a further three. Non-haematological toxicity was minor. Thus, despite demonstrable activity in SCLC and melanoma, unpredictable myelosuppression is likely to preclude further assessment in combination chemotherapy regimes in these tumours.

Adult↗

High-dose cyclophosphamide and VP 16 as late dosage intensification therapy for small cell carcinoma of lung.

This study investigated the use of late dose intensification therapy (LDIT) with cyclophosphamide (180 mg/kg) and VP 16 (1 g/m2) plus autologous bone marrow rescue in 22 patients with small cell lung cancer (SCLC). These patients were selected from a group of 95 patients who received three courses of a five-drug induction regimen comprising cyclophosphamide (750-1000 mg/m2), adriamycin (40 mg/m2), VP 16 (100 mg/m2) for 3 days, methotrexate (50 mg/m2) and vincristine (2 mg) (CAVMO). There were 16 patients with limited disease, 8 of whom were in complete remission (CR) and 8 in partial remission (PR) after the induction therapy. The other 6 patients had extensive disease; 3 of these achieved CR and 3 PR after induction therapy. Of the 11 patients in PR, 5 responded to LDIT; 3 had a further PR, and 2 CR. Subsequent to LDIT radiotherapy 4000 cGy was given to the primary site in 10 of the 22 patients. Since the start of the study, 19 of the 22 patients have relapsed and died (median survival 11 months), while 3 remain alive and in remission at 11, 11, and 24 months. Comparison of the survival of patients receiving LDIT with that of an equivalent group (with respect to staging and response to induction chemotherapy) of patients who received induction chemotherapy alone showed no significant difference. In this study, LDIT following conventional induction therapy in patients with chemosensitive tumours did not improve survival.

Antineoplastic Combined Chemotherapy Protocols↗

The role of VP-16 in the treatment of small-cell lung cancer: studies of the West of Scotland Lung Cancer Group.

Reviews of published studies indicate that the incorporation of VP-16 (Vepesid) into combination chemotherapy for small-cell lung cancer may improve overall response rates from 50% to between 65% and 80%. In addition, high-dose VP-16 may yield a higher response rate than that obtained with conventional doses. The West of Scotland Lung Cancer Group has therefore conducted studies to examine the effects of VP-16 both in a combination regimen as induction therapy and (together with high-dose cyclophosphamide) as late intensification therapy in high dose, aimed at preventing relapse in responding patients. Response to induction treatment improved with the addition of VP-16, compared to earlier studies carried out by the group, yielding an overall response rate of 80% for patients with limited disease and 62% for those with extensive disease. Although induction therapy comprised only three courses (lasting 9 weeks), the median response duration of 9.5 months for complete responders and the median survival of 14 months for complete responders (limited disease) were in keeping with those obtained using more prolonged induction therapy. The intensification therapy with high-dose cyclophosphamide and high-dose VP-16, however, yielded no improvement in overall survival in those responding patients who received it compared with those who did not. Radiotherapy following late-dose intensification prevented local tumor recurrence but appeared to have no effect on overall survival. Resistance to VP-16 and other drugs is a possible deterrent to successful therapy in small-cell lung cancer, and it is suggested that research focus on a possible role for calcium channel blockers in circumventing drug resistance.

Carcinoma, Small Cell↗