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Biomedical subjects

D Cunningham

Publications and source records attributed to D Cunningham.

At least 325 records · Page 18Linked to original sources
PubMed1985

Alfacalcidol as a modulator of growth of low grade non-Hodgkin's lymphomas.

Ten patients with low grade non-Hodgkin's lymphoma (seven follicular small cleaved and three small lymphocytic) were treated with 1 microgram oral alfacalcidol (1 alpha-hydroxycholecalciferol) daily. Of the seven patients with lymphomas of follicular small cleaved subtype, one achieved complete and three partial remission, whereas none of three patients with small lymphocytic lymphomas responded. In seven of the 10 patients, 1,25(OH)2D3 receptors were measured in tissue from lymph nodes, and a positive correlation between the presence and amount of receptor and response to alfacalcidol was found. These preliminary data suggest that alfacalcidol has appreciable antitumour activity in low grade non-Hodgkin's lymphomas.

Adult↗
PubMed1985

Comparison of serum and cerebrospinal fluid levels of methotrexate in man during high-dose chemotherapy for aggressive non-Hodgkin's lymphoma.

The relationship between plasma and cerebrospinal fluid levels of methotrexate was studied in five patients, four with aggressive non-Hodgkin's lymphoma and one with mixed epithelial mesothelial tumour, who were treated with high-dose methotrexate (1.5 g/m2) as part of combination chemotherapy. Cerebrospinal fluid was sampled for 24 h via a permanent indwelling lumbar catheter. No complications were observed with this technique. In two patients with central nervous system involvement adequate "cytotoxic" levels (greater than 10(-6) M) were obtained for greater than 12 h. The remaining three patients, with no direct evidence of central nervous system involvement, never attained adequate cytotoxic methotrexate levels in the cerebrospinal fluid. Serum levels were therapeutic in all patients. These results suggest that patients with central nervous system tumour involvement may receive adequate doses of methotrexate in the cerebrospinal fluid. Patients with occult central nervous system tumour involvement may not attain adequate cerebrospinal fluid levels. A 24-h serum methotrexate level of greater than 10(-5) M may indicate that patients have achieved therapeutic cerebrospinal fluid levels of methotrexate. Cranial irradiation following chemotherapy is still recommended in this tumour group until adequate cytotoxic levels of methotrexate can be obtained in all patients for prolonged periods.

Adult↗
PubMed1985

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↗
PubMed1985

Functional and structural changes of the human proximal small intestine after cytotoxic therapy.

The effects of cytotoxic therapy on the structure and function of the proximal jejunum were studied in six patients receiving intravenous cyclophosphamide (300 mg/m2), methotrexate (40 mg/m2), and 5-fluorouracil (600 mg/m2) as adjuvant therapy for breast cancer. Using a steady state, triple lumen tube perfusion system the absorption of water and electrolytes was measured before and 48 h after administration of the cytotoxic agents. Jejunal biopsies were obtained at each perfusion. Median (range) water absorption fell from 126 (40-142) to 84 (46-142) ml/h/30 cm, with parallel changes for electrolytes; none of the changes was significant. Brush border disaccharidases did not change at 48 h after chemotherapy, while mature enterocytes appeared normal by both light and electron microscopy. Crypt cells and immature enterocytes, however, showed focal vacuolation by light microscopy, corresponding to the occurrence of large residual bodies (secondary lysosomes) containing partially degraded fragments of damaged crypt cells. The confinement of ultrastructural changes to the immature cell population may explain the failure of this study to show a consistent change in the absorptive function of the jejunum 48 h after chemotherapy.

Adult↗
PubMed1985

Measuring the impact of health interventions: a review of available instruments.

Interest in the measurement of the impact of health services has been increasing for three main reasons. Policy makers and service providers wish to be reassured that they are: (i) benefitting the public for whom the service is provided; (ii) in times of economic recession and limited resources, achieving the 'best value for money'; and (iii) given the need to make economies in health expenditures, maintaining standards of the health care. Recent developments in information for the evaluation of health services have tended to emphasis the control and monitoring of expenditure in preference to the control and monitoring of quality. There is concern that this might lead to adverse consequences for patients and for the health service as a whole in that the quality of services provided might deteriorate. Health interventions are considered to be successful if they result in a beneficial change in the health of the population for whom they are provided. If the health of the population is not improved, or maintained, questions are raised about either the appropriateness of the intervention in relation to health policies which have been selected, or about the quality of the care which has been provided. Because of this, it is necessary to monitor both the outcome of a heath intervention in terms of the change in the level of health of the population, and also to measure the quality and the effectiveness of the care provided. Health services research has, over the years, developed a number of different types of measures which can be applied to health services and has suggested a number of applications for such measures in terms of the impact on the health of patients and the general population and the quality and effectiveness of health services. The first section of this paper reviews a selection of measures for both health and the effects of health interventions and discusses their applicability as management tools. The use to which such measures are put obviously depends upon the type of decisions which they are to inform, which in turn are dependent upon the organisational level at which the decision is to be made, and the policy objectives of the service to which they relate. The second part of the paper discusses factors which must be taken into account when choosing measures to monitor the impact of the health services. In examining the suitability of a management tool, a measure must be proven to provide information which is universally acceptable and which conforms to a number of scientific standards.(ABSTRACT TRUNCATED AT 400 WORDS)

England↗
PubMed1985

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↗
PubMed1985

Macular deposits in galactokinase deficiency.

Deficiency of the enzyme, galactokinase, is a recognized cause of "juvenile" lens opacities; these opacities are felt to be its only clinical expression. The deficiency itself is inherited as an autosomal recessive and as such is expected to be clinically manifest in the homozygote. We have recently demonstrated cataracts and associated bilateral macular deposits in a white male who is heterozygous for the deficiency of the enzyme and whose dietary intake of milk and its products is extremely high. To our knowledge, intraretinal deposits have not previously been described in patients with galactokinase deficiency, and their clinical significance and biochemical makeup can only be speculative. Dietary restriction of galactose is recommended for all individuals proven to be deficient in this enzyme, whether homozygous or heterozygous.

Adult↗
PubMed1984

Progression of pseudovitelliform macular dystrophy.

Pseudovitelliform macular dystrophy is a dominantly inherited macular disorder. It is characterized by the presence of horizontally oval yellowish deposits within the maculas that are approximately one-third disc diameter in size. As classically described, progression of the lesions over a follow-up period of as long as six years has not been described and the prognosis for retention of good visual function is excellent. We report the ophthalmoscopic appearance of six eyes of three patients from a very subtle alteration of macular pigmentation to severe disruption of macular architecture, and demonstrate in one of our patients drastic deterioration in both ophthalmoscopic appearance and visual function over a three-year period of follow-up. The prognosis for retention of good vision in this disorder must include the possibility of the eventual development of severe visual impairment.

Adult↗
PubMed1984

Advanced gastric cancer: experience in Scotland using 5-fluorouracil, adriamycin and mitomycin-C.

Eighty-four patients with advanced gastric cancer treated in four centres in Scotland between June 1980 and December 1982 were reviewed following treatment with 5-fluorouracil, adriamycin and mitomycin-C (FAM). Eighty-one patients were evaluable. Twenty-eight patients (35 per cent) responded (four complete) with a median duration of response of 10.5 months and median survival of 17 months. Ten are still alive. Response was associated with an improvement in performance status. Eight patients (10 per cent) had stable disease with a median survival of 10 months. Forty-five (55 per cent) had progressive disease with a median survival of 4.5 months; one patient remains alive. Analysis of prognostic variables indicated that the presence of hepatic metastases had a negative influence on response to FAM (P less than 0.001). Treatment was well tolerated on an outpatient basis. FAM offers good palliative therapy in a proportion of patients with this disease, especially those without overt liver metastases.

Adenocarcinoma↗
PubMed1984

Treatment of advanced ovarian cancer with combination chemotherapy using cyclophosphamide, adriamycin and cis-platinum.

Fifty-four patients with advanced ovarian cancer have been treated with combination chemotherapy using cyclophosphamide, adriamycin and cis-platinum. The toxicity of the regimen was manageable but few patients were prepared to tolerate more than 6 months of treatment. Those in complete clinical remission at that time were offered second-look laparotomy and if apparently free of disease, therapy was discontinued. Forty-seven patients could be assessed of whom 33 had had no previous therapy. Twenty-two of these were clinically free of disease after completion of chemotherapy of whom 12 had no detectable disease at second-look laparotomy. Of 14 patients who had failed previous therapy only one remains clinically free of disease. The results in the untreated patients demonstrate the primary importance of bulk reduction at initial laparotomy. The use of the regimen in patients who have failed on previous treatment or in patients with bulk disease seems to be palliative and the toxicity should be assessed in this context.

Adult↗
PubMed1983

A randomised multicentre single blind comparison of a cannabinoid anti-emetic (levonantradol) with chlorpromazine in patients receiving their first cytotoxic chemotherapy.

One hundred and eight patients selected to receive combinations of highly emetic cytotoxic chemotherapy for malignant disease were included in a study of anti-emetic therapy. The patients were randomly allocated to receive levonantradol (0.5, 0.75 or 1 mg) or chlorpromazine (25 mg) prior to receiving their first course of cytotoxic therapy. The appropriate anti-emetic was administered 2 hr prior to the start of chemotherapy, 2 hr after chemotherapy and subsequently at 4-hourly intervals for a further 8 hr. The extent of anorexia, nausea and vomiting along with other side-effects were assessed at regular intervals by physicians and nursing staff during the 24 hr following chemotherapy. In addition, a self-assessment questionnaire was completed by the patients. Levonantradol (0.5 mg) was superior to chlorpromazine (25 mg) as an anti-emetic. Both were reasonably well tolerated, although at this dose of levonantradol 22% of patients experienced dysphoric reactions. At higher doses of levonantradol the proportion of patients experiencing these reactions rose to 50%, but without a concomitant increase in antiemetic activity. Neither drug achieved satisfactory control of vomiting in patients receiving combinations containing cis-platinum. We conclude that levonantradol (0.5 mg) is a more effective anti-emetic than chlorpromazine (25 mg) in patients receiving cytotoxic chemotherapy. However, its use cannot be recommended due to its high incidence of unacceptable central nervous system side-effects.

Adolescent↗