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Biomedical subjects

D R Bell

Publications and source records attributed to D R Bell.

At least 109 records · Page 6Linked to original sources
PubMed1987

The chemotherapy of onchocerciasis. XII. The prediction of microfilarial loads in patients with onchocerciasis after treatment with diethylcarbamazine in northern Ghana.

This paper presents some statistical problems of analysing changes in patterns of microfilarial loads in onchocerciasis patients after chemotherapeutic treatment. Analyses are made of a pooled set of data from ten separate studies of diethylcarbamazine (DEC) conducted at the Onchocerciasis Chemotherapeutic Research Centre, Tamale, between 1978 and 1983. Regression models of microfilarial load at different intervals post-treatment are fitted with initial microfilarial load, total dose of DEC, duration of treatment and age of the patient as the independent variables. Appropriate transformations of the variables are chosen by examination of plots of residuals for violations of the assumptions underlying the regression models. A dose response curve for DEC is produced.

Adult↗
PubMed1986

Multidrug resistance.

Multidrug resistance describes a complex phenotype whose predominant feature is resistance to a wide range of structurally unrelated cytotoxic compounds, many of which are anticancer agents. This phenotype occurs frequently in mammalian cell lines and transplantable tumours selected for resistance to a single drug. Reduced cellular accumulation of the drugs involved appears to account for the resistance. This may be a consequence of reduced drug influx, increased drug efflux, or both. A wide variety of biochemical changes have been identified in multidrug resistant cell lines, the most consistent of which is the increased expression of P-glycoprotein, a conserved, high molecular weight, plasma membrane glycoprotein. The level of P-glycoprotein expression correlates with the degree of drug resistance in a variety of different cell types. In a number of multidrug resistant cell lines, overexpression of P-glycoprotein results from gene amplification. While the function of P-glycoprotein is unknown, independent lines of evidence support the notion that P-glycoprotein is the causative molecule mediating the multidrug resistance phenotype. Significant levels of P-glycoprotein expression have been detected in some biopsy specimens from patients with ovarian and sarcoma tumours. These findings suggest that multidrug resistant tumour cells can occur in human malignancies. The presence of such cells may affect the outcome of chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1985

cis-Diamminedichloroplatinum-induced hypomagnesemia and renal magnesium wasting.

Hypomagnesemia is a well-recognised complication of cis-diamminedichloroplatinum (DDP) treatment. We prospectively evaluated 50 patients with advanced malignant disease receiving DDP for the development of hypomagnesemia. Urinary magnesium excretion was measured in 24 patients. The mean serum magnesium fell from 0.79 mmol/l (normal 0.7-1.1 mmol/l) prior to therapy to 0.55 mmol/l 3 months after commencing DDP. All 50 patients had become hypomagnesemic by this time and 10% were symptomatic, requiring oral magnesium supplementation. At 6 weeks after commencing DDP only four patients had restricted urinary magnesium excretion to less than 1.0 mmol/day. The other patients clearly had inappropriately high levels of urinary magnesium excretion, suggesting that DDP may induce a renal tubular defect in magnesium conservation. Hypomagnesemia is a common complication of DDP therapy which in many patients is asymptomatic. Further, more detailed studies of renal magnesium handling are necessary to determine fully the effect of DDP on urinary magnesium excretion.

Adult↗
PubMed1985

Functional bases for individualities among vascular smooth muscles.

This review deals with cellular factors that contribute to individualities of vascular smooth-muscle function in different organ systems and at different levels of the vascular tree. Particular attention has been given to: membrane receptors responsive to catecholamines, serotonin, angiotensin II, dopamine, and acetylcholine; membrane properties, including resting and action potentials, and the Na+, K+ ATPase electrogenic pump; regulation of cellular Ca2+; contractile proteins; metabolism, and cell messengers. Differences in membrane receptors appear to be the major basis for the individualities found in various vascular smooth muscles. Differences in cell-membrane properties and Ca2+ regulation are also significant causes of variability. Cell metabolism and contractile proteins contribute relatively less to the individualities of vascular smooth muscle. Too little is known about cell messengers to assess their contribution to this individuality.

Animals↗
PubMed1985

Intestinal hemodynamics in dogs with chronic one-kidney, one-wrapped hypertension.

In pentobarbital-anesthetized dogs with chronic one-kidney, one-wrapped perinephritic hypertension, the status of blood flow and resistance differs among vascular beds. There is normal blood flow with elevated resistance in the limb and elevated blood flow with normal resistance in the ileum. In the present study we investigated the mechanism of elevated flow and normal resistance in the ileum by measuring blood flow, pressure, O2 consumption, reactive hyperemia, pressure-flow relationships, resistance at maximal vasodilation, and nonentrapment (shunting) of 9-microns microspheres in vascularly isolated, blood-perfused ilea of 11 24-h fasted dogs with chronic (greater than 4 wk duration) one-kidney perinephritic hypertension [1KH; PA = 163 +/- 8 (SD) mmHg] and 15 fasted normotensive one-kidney, sham-wrapped dogs (1KC; PA = 108 +/- 7 mmHg). In 1KH ileal blood flow was elevated by 35% (P less than 0.001), but ileal vascular resistance was unchanged. Pressure-flow relationships were similar in hypertensive and normotensive ilea, with little evidence for significant autoregulation in either. We also noted no significant differences in ileal O2 consumption, reactive hyperemia, or resistance at maximal vasodilation. However, we found nonentrapment of microspheres to be a positive function of perfusion pressure (P less than 0.02) and to be increased by 40% during ileal perfusion at levels of perfusion pressure within the hypertensive range (150-200 mmHg). Thus the increased ileal blood flow in 1KH may reflect the effects of a poorly autoregulating tissue, as well as "shunt" flow through pressure-activated channels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Detection of P-glycoprotein in ovarian cancer: a molecular marker associated with multidrug resistance.

A multidrug resistance phenotype is frequently observed in animal and human cell lines selected for in vitro resistance to a single chemotherapeutic agent. Overexpression of a highly conserved cell-surface glycoprotein (P-glycoprotein) is consistently associated with this phenotype in these mutant lines. A monoclonal antibody against P-glycoprotein was used to examine tumor samples from five patients with advanced ovarian cancer for evidence of P-glycoprotein overexpression. High levels of P-glycoprotein were detected in samples from two patients suggesting that a multidrug resistance mutation may also occur in ovarian cancer. This finding has broad implications for the understanding of nonresponse to chemotherapy in a variety of human neoplasms, and may provide a rational explanation for failure of chemotherapy in treatment of advanced ovarian cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1984

High-dose methotrexate with leucovorin rescue, vinblastine, and bleomycin with or without tamoxifen in metastatic renal cell carcinoma.

A regimen of high-dose methotrexate with leucovorin rescue, vinblastine, and bleomycin with or without tamoxifen was administered to 34 patients with metastatic renal cell carcinoma. No complete remissions were observed, but ten patients (30%) achieved partial remission and an additional 13 patients (39%) had stabilization of disease. The median survival of responding patients (110 weeks) was significantly longer than that of nonresponding patients. The addition of tamoxifen did not influence response or survival. This regimen was tolerated without significant toxicity. A prospective randomized study of the vinblastine and high-dose methotrexate regimen compared to the respective single agents seem to be indicated.

Adenocarcinoma↗
PubMed1983

Extravascular distribution of albumin and IgG during high-permeability edema in skin.

The effects of local intra-arterial infusions of bradykinin on the interstitial distribution of albumin and gamma-immunoglobulin G (IgG) was studied in hind paw skin of anesthetized rabbits. After 4 h of a continuous bradykinin infusion, lymph flow in a prenodal popliteal lymphatic was five times base line. The lymph-to-plasma concentration ratio for total protein was increased by 34%. Samples of heel skin were taken at the end of the experiment. The extracellular and plasma spaces in the tissue samples were measured using 51Cr-labeled ethylenediaminetetraacetic acid and 125I-labeled human serum albumin, respectively. The protein spaces were calculated from measurements of endogenous albumin and IgG concentrations using rocket electroimmunoassay. After bradykinin, the interstitial volume was 28% greater than control, whereas the extravascular masses of albumin and IgG were twice as great as the control values. Based on lymph concentration, both proteins distributed in 50% of the interstitial volume during control. Following bradykinin, both proteins distributed in a greater fraction of the interstitium. However, the excluded volume, equal to 0.9 ml/g dry wt, was not altered after bradykinin. This may indicate an increase in free-fluid channels with no hydration of the interstitial gel matrix.

Animals↗
PubMed1982

Alternating non-cross-resistant combination chemotherapy for small cell anaplastic carcinoma of the lung.

The development of drug resistance limits the survival or patients with small cell anaplastic carcinoma of the lung (SCLC). The present study was undertaken to overcome this problem by administering two alternating noncross resistant combination chemotherapy regimens. One-hundred-one patients were entered on study, and 98 were evaluable, with a median onstudy time of 55+ weeks. All patients received the initial combination therapy of cyclophosphamide, methotrexate, and vincristine, alternating every three weeks with Adriamycin and VP16-213 (etoposide). Radiation therapy was not a standard part of protocol. Thirty-two patients had regional disease (LD), and 66 had extensive disease (ED). Overall, 76% of patients responded to this therapy with 30 (31%) complete remission (CR) and 44 (45%) partial remissions (PR); the respective CR and PR rates were 31% and 50% for LD, and 30% and 42% for ED patients. Myelosuppression was the principal toxicity with a leukocyte nadir of 2.0 X 10(9)/1 in 10% of cycles. Septicemia in six neutropenic ED patients with progressive disease contributed to the only treatment-related deaths. Patients entering CR had a median survival greater than 51 weeks (range, 8-150+); 58+ for LD and 49+ for ED patients. Patients in PR had respective median survivals of 33+ (overall), 43+ (LD), and 24+ (ED) weeks. Forty patients have had relapses with initial sites being local sites in 35%, and neurologic in 38%. Although this protocol has not discernibly delayed the onset of drug resistance, the problem should be considered when new protocols are designed in SCLC.

Antineoplastic Agents↗
PubMed1982

Advanced ovarian cancer: a prospective randomised trial of chlorambucil versus combined cyclophosphamide and cis-diamminedichloroplatinum.

Thirty-seven patients with advanced ovarian cancer were treated in a prospective, randomised trial comparing chlorambucil with a combination of cyclophosphamide and cis-diamminedichloroplatinum (cis DDP). Treatment with the combination was associated with an increased overall response rate (69% versus 23%) (p = 0.04). A response was associated with a longer median survival but no survival advantage was demonstrated for patients who received cyclophosphamide/cis DDP. A larger study is needed to evaluate fully the potential of regimens containing cis DDP in the management of advanced ovarian cancer.

Chlorambucil↗