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Biomedical subjects

D Cunningham

Publications and source records attributed to D Cunningham.

At least 361 records · Page 20Linked to original sources
PubMed1986

Continuous ambulatory pulmonary artery pressure monitoring. A new method using a transducer tipped catheter and a simple recording system.

A transducer tipped catheter and simple recording system were used for the continuous measurement of ambulatory pulmonary artery pressure. The pulmonary artery pressure was recorded on a miniaturised tape recorder and replayed via an optical writer. Pulmonary arterial systolic and diastolic pressures can be analysed on a beat to beat basis. Continuous ambulatory monitoring was performed for a total 288 hours in 13 patients who were undergoing routine investigation for coronary artery disease. There was less than 1% zero drift and 0.25% linearity error per full scale pressure. The frequency response of the entire system was flat to 8 Hz with a linear phase delay. The transducer tipped catheter and a conventional fluid-filled system were used to measure left ventricular and pulmonary artery end diastolic pressures in eight patients. The correlation between the results obtained by the two methods was excellent. This method could be used at any centre equipped for ambulatory electrocardiographic monitoring.

Adult↗
PubMed1986

Use of Leu M1 and antiepithelial membrane antigen monoclonal antibodies for diagnosing Hodgkin's disease.

Biopsies of 82 patients diagnosed as having Hodgkin's disease were reviewed. Seventeen were reclassified histologically as non-Hodgkin's lymphoma or reactive lymphoid hyperplasia. A substantial number of cases of Hodgkin's disease were negative when stained with Leu M1. Staining for Leu M1 was not found in the cases of non-Hodgkin's lymphoma or reactive lymphoid hyperplasia. With the exception of the lymphocyte predominant nodular subtype of Hodgkin's disease, epithelial membrane antigen staining was seen in a few cases of Hodgkin's disease and non-Hodgkin's lymphomas. This was not a useful discriminating feature.

Antibodies, Monoclonal↗
PubMed1986

T-cell lymphoblastic lymphoma of the uterus complicated by Chlamydia trachomatis pneumonia.

This is the first documented case of a T-cell lymphoblastic lymphoma arising in the uterus. At presentation, the patient also had a life-threatening pneumonia due to Chlamydia trachomatis which responded to erythromycin and tetracycline. Cytotoxic therapy produced partial tumour regression, but the patient died 14 weeks after diagnosis, probably as a result of intercurrent infection.

Adult↗
PubMed1986

Short duration combination chemotherapy in the treatment of small cell lung cancer.

Ninety five patients (57 with limited disease and 38 with extensive disease) with previously untreated small cell lung cancer were entered into a study of short duration combination chemotherapy with intravenous cyclophosphamide (750 mg/m2) on day 1, adriamycin (40 mg/m2) on day 1, and etoposide VP-16 (100 mg/m2) on days 1, 2, and 3, with the addition on day 10 of methotrexate 50 mg/m2 with folinic acid rescue and vincristine 2 mg. The treatment was repeated on day 22 and only three courses were given. No maintenance chemotherapy was given, though patients with a complete response received radiotherapy (30-40 Gy (3000-4000 rads] to the primary site in most cases. Forty nine patients (86%) with limited disease achieved a response, with 26 (46%) complete remissions. Twenty five patients (66%) with extensive disease had a response, but only eight (21%) had a complete response. Actuarial survival analysis for the whole patient population showed a median survival of 13 months for patients with limited disease and seven months for those with extensive disease. The median survival was 14 months for those patients with limited disease who achieved a complete response, but only 10 months for non-responders. Myelosuppression was the major expression of toxicity. There were three deaths related to treatment and seven patients had febrile episodes during neutropenia that required antibiotics. Mucositis, which was usually mild, occurred in 49% of patients. The primary site was the main site of initial relapse in 56% of the patients who relapsed. Among patients with limited disease who achieved a complete response, relapses at the primary site were less common in those who received radiotherapy (five out of 12) than in those who did not (all eight). The results indicate that this short duration chemotherapy in small cell lung cancer gives response rates and the potential for long term survival similar to those obtained in other series while allowing patients the maximum time free from treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Phase I and pharmacokinetic study of LM985 (flavone acetic acid ester).

We have conducted a Phase I and initial clinical pharmacological evaluation of LM985, the first of a series of compounds based on the flavone ring structure to be considered for clinical trial in malignant disease. The drug was administered i.v. to 26 patients with advanced cancer on an every-21-day schedule. Patients were treated at 14 dosage levels ranging from 10 to 1500 mg/m2. Dose limiting toxicity was identified as acute reversible hypotension occurring during drug infusion; no leukopenia, alopecia, hepatic toxicity, or renal toxicity was observed, but at the higher dose range, mild sedation was apparent. Twenty patients had measurable disease and were evaluable for response. One patient with colorectal carcinoma had stable disease after three courses of LM985; however, no other responses were seen. Pharmacokinetic and in vitro drug degradation studies imply that the ester LM985 is hydrolyzed to LM975 (flavone acetic acid) rapidly in vivo. LM975 is active in a variety of animal tumor models, but it does not have the cardiovascular side effects seen with LM985 (hypotension and bradycardia) in pithed or anesthetized rats. We would recommend that LM975 be considered for clinical trial, because it seems likely that substantially higher doses of LM975 than of LM985 can be given without dose limiting cardiovascular toxicity.

Adult↗
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↗