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Biomedical subjects

M McBride

Publications and source records attributed to M McBride.

At least 37 records · Page 2Linked to original sources
PubMed1997

Mortality and cancer incidence among sawmill workers exposed to chlorophenate wood preservatives.

OBJECTIVES: This study examined the association between exposure to chlorophenates and the risk of soft tissue sarcoma; non-Hodgkin's lymphoma; Hodgkin's disease; and cancers of the lung, nose, and nasopharynx. METHODS: A retrospective cohort study was conducted of 26487 workers employed for at least 1 year between 1950 and 1985 in 11 chlorophenate-using and 3 non-using sawmills in British Columbia, Canada. Exposures by job were ascertained with interviews of senior employees. RESULTS: Probabilistic record linkage to the Canadian Mortality Data Base and the British Columbia Cancer Registry found 4710 deaths between 1950 and 1990, and 1547 incident cases of cancer between 1969 and 1989. None of the cancers of interest had elevated mortality related to chlorophenate exposure. Non-Hodgkin's lymphoma incidence (n = 65) increased with increasing chlorophenate exposure hours, yielding the following standardized incidence ratios: less than 120 hours 0.68; 120 to 1999 hours, 0.59; 2000 to 3999 hours, 1.04; 4000 to 9999 hours, 1.02; and 10000 or more hours, 1.30. CONCLUSIONS: These results are consistent with the borderline positive associations seen in other recently reported studies of chlorophenate-exposed workforces.

British Columbia↗
PubMed1997

Who gets a heart? Rationing and rationalizing in heart transplantation.

National policy on organ transplantation is made by the United Network for Organ Sharing (UNOS), a representative body composed of health care professionals and patients. Standardized criteria for determining when a patient should be placed on the waiting list for heart transplantation are now in effect nationwide. Current and future directions to maximize the utilization of available donated organs are explored.

Guidelines as Topic↗
PubMed1995

Reversible AIDS-related sclerosing cholangitis.

Although hepatobiliary involvement is common in the acquired immunodeficiency syndrome, it infrequently leads to biliary tract abnormalities. We describe a 39-year-old man with human immunodeficiency virus infection and no previous acquired immunodeficiency syndrome-defining illnesses, who presented with malaise, right upper quadrant pain, lymphadenopathy and cholestasis. An endoscopic retrograde cholangiopancreatography demonstrated sclerosing cholangitis due to disseminated B-cell nonHodgkin's lymphoma. Following chemotherapy, his symptoms and signs rapidly improved, so that 1 month later his endoscopic retrograde cholangiopancreatography had returned entirely to normal.

Adult↗
PubMed1995

Evaluation of safety and efficacy of 3TC (lamivudine) in patients with asymptomatic or mildly symptomatic human immunodeficiency virus infection: a phase I/II study.

In a phase I/II study, 7 levels of 3TC therapy (from 0.5 to 20.0 mg/kg/day) were studied in 104 asymptomatic and mildly symptomatic human immunodeficiency virus-infected patients with CD4 cell counts < or = 400 x 10(6)/L. Mild and transient episodes of diarrhea, headache, fatigue, nausea, and abdominal pain were the most frequent events reported. No dose-limiting toxicities were observed. Small and transient increases in CD4 cell counts were detected during the first 4 weeks of treatment. These were followed by progressive declines during prolonged therapy. Sustained decreases in beta 2-microglobulin, neopterin, and p24 antigen levels were seen over the 52-week study. There was no consistent dose-response correlation for any surrogate marker. Penetration of 3TC into cerebrospinal fluid (CSF) was in the same range as reported for ddC and ddI; the mean CSF-to-serum ratio was 0.06. These findings indicate that 3TC exhibits an excellent safety profile and has antiretroviral activity at the dosages studied.

Adult↗
PubMed1995

An overview of transplantation in Australia.

Organ donation in Australia has permitted transplantation of the kidneys, heart, lung, pancreas, liver and cornea. Each of these programs has successfully provided life and rehabilitation to Australians with end-stage failure of one or more organs. The programs are supported by an infrastructure of donor coordinators, matching and allocation procedures and national co-operative registries, which record and publish the outcome of each form of transplant. Four national organizations work to promote transplantation: the Transplantation Society of Australia and New Zealand; the Australasian Transplant Coordinators' Association; the Australian Kidney Foundation; and the Australian Co-ordinating Committee for Organ Registries and Donation. Australian donation rates are lower than in many, but not all, comparable developed democracies, however utilization of those donor offers is high, leading to 698 organ transplants being performed in 1993.

Australia↗
PubMed1995

Phase I trial of high-dose tamoxifen as a modulator of drug resistance in combination with daunorubicin in patients with relapsed or refractory acute leukemia.

Tamoxifen and its main metabolite N-desmethyltamoxifen (NDMTmx) have been shown to increase intracellular daunorubicin (DNR) levels in human leukemia cell lines that display the multidrug resistant (MDR) phenotype. We designed a phase I dose escalation study of Tmx (200-700 mg/day p.o. for 7 days) in combination with a fixed dose of DNR (50 mg/m2 intravenously on days 5, 6 and 7) in patients with advanced leukemia to determine whether this combination could be given safely and whether plasma levels of 10 microM, the effective in vitro MDR modulator concentration, could be achieved. Pharmacologic studies of Tmx, NDMTmx and DNR, and its main metabolite daunorubicin-ol (DNR-ol) were performed as was determination of P-glycoprotein (Pgp) using a monoclonal antibody that recognizes an external epitope of the molecule. A total of 14 patients (median age 50, range 22-67) were treated at the following dose levels: 200 mg/day: three patients; 400 mg/day: four patients; 550 mg/day: three patients; and 700 mg/day: four patients. Two patients with relapsed AML achieved remission. Toxicity of the combination was similar to that seen with DNR alone and no severe hepatic, cardiac or retinal toxicity was noted. Plasma Tmx levels approached 7 microM at the two highest dose levels studied; plasma levels of NDMTmx were slightly less. The area under the curve for DNR and its main metabolite daunorubicin-ol (DNR-ol) did not show significant changes with escalation of Tmx dose. This phase I study suggests that concentrations of Tmx high enough to reverse the MDR phenotype can be approached and that the combination of high-dose Tmx with a standard dose of DNR has an acceptable toxicity profile. More evaluation in phase II studies is necessary to define further its role as an MDR modulator.

Adult↗
PubMed1994

GPs and managers. What the doctors saw.

Low morale among many GPs was the trigger for a survey which examined the causes of communication breakdowns and misunderstandings. Mollie McBride and colleagues outline the results.

Administrative Personnel↗
PubMed1994

Comparative activity of tamoxifen and N-desmethyltamoxifen in human multidrug resistant leukemia cell lines.

Tamoxifen (Tmx) is one of a number of agents that can reverse the multidrug resistant (MDR) phenotype in vitro; it is unique, however, in that both the parent compound and the main metabolite, N-desmethyltamoxifen (NDMTmx), have long plasma half-lives, 7 and 14 days, respectively. To determine whether NDMTmx was as active as the parent compound in restoring sensitivity to daunorubicin (DNR) in vitro, we performed uptake and retention studies in the MDR-positive human leukemia cell lines CEM-VLB and HL-60/RV+ using laser flow cytometry to quantitate intracellular DNR concentration. Cells incubated with DNR and NDMTmx 10 microM demonstrated increased intracellular DNR levels that were very similar to those obtained with DNR and Tmx 10 microM. Cellular retention of DNR was also measured after incubation with Tmx 10 microM or NDMTmx 10 microM and resuspension in fresh medium containing Tmx or NDMTmx in order to stimulate in vivo conditions. Washout curves in both cell lines were similar with both Tmx and NDMTmx. Finally, clonogenic experiments were performed to determine whether Tmx and NDMTmx demonstrated the same degree of cytotoxicity. The combination of Tmx 10 microM plus DNR and that of NDMTmx 10 microM plus DNR each resulted in > 80% growth inhibition. These results suggest that NDMTmx is as active as Tmx in restoring sensitivity to DNR in vitro, a finding which may have important implications in clinical trials that assess the ability of Tmx to reverse the MDR phenotype.

Daunorubicin↗
PubMed1993

Outpatient follow-up in women with HIV infection in Parkside Health Authority (UK).

OBJECTIVE: To describe patterns of attendance for follow-up among HIV infected women in Parkside, UK and their correlates. DESIGN: Retrospective cohort study. SUBJECTS: 103 HIV infected women. MAIN OUTCOME MEASURES: Whether patients attended for follow-up between three and 18 months. RESULTS: 31% of women were married and 46% had children. Women born in sub-Saharan Africa were significantly less likely to attend for follow-up after three months (56%) than women born in other areas who had acquired HIV either heterosexually (82%) or through injecting drug use (81%). This pattern persisted on multivariate analysis controlling for whether women were symptomatic, had had a previous positive test, were married or had children. CONCLUSIONS: HIV positive sub-Saharan African women are less likely to reattend for follow-up than women with heterosexually acquired HIV from other areas or those who acquired infection through intravenous drug use. Further studies are needed to identify barriers to follow-up for women and to shape the development of more appropriate and accessible services for HIV infected women, especially those of sub-Saharan African origin.

Adult↗
PubMed1992

Comparative cellular pharmacology of daunorubicin and idarubicin in human multidrug-resistant leukemia cells.

We examined the effect of daunorubicin (DNR), the new anthracycline derivative idarubicin (IDR), and verapamil on two leukemia cell lines that displayed the multidrug resistant (MDR) phenotype and used laser flow cytometry to quantitate intracellular anthracycline content. The vinblastine-resistant human lymphoblastic leukemia cell line CEM-VBL demonstrated minimal DNR uptake; simultaneous incubation with verapamil and DNR increased intracellular DNR uptake fourfold. IDR uptake was 10 times more rapid in these cells and simultaneous incubation with IDR and verapamil resulted in only a 1.2-fold increase of intracellular IDR. Similar results were observed in the vincristine-resistant human myeloid leukemia cell line HL-60/RV+. Intracellular retention of DNR and IDR was also measured in each cell line. In CEM-BVL cells, 38% of the original DNR concentration remained after a 2-hour resuspension in fresh medium compared with 71% of the original IDR concentration. In HL-60/RV+ cells, 36% of the DNR concentration remained compared with 51% of the IDR concentration. After incubation of CEM-VBL and HL-60/RV+ cells with DNR for 1 hour followed by resuspension in fresh medium plus verapamil, intracellular DNA retention increased 5- and 5.2-fold, respectively. However, incubation of these cells for 1 hour with IDR followed by resuspension in fresh medium plus verapamil resulted in only a 1.6- and 2.4-fold increase in intracellular IDR retention. Lastly, clonogenic experiments were performed to correlate intracellular anthracycline content with cytotoxicity. DNR alone had a minimal effect on the clonogenic growth of CEM-VBL cells, whereas the combination of DNR plus verapamil resulted in approximately 80% growth inhibition. However, incubation of these cells with IDR alone resulted in greater than 95% growth inhibition. These results suggest that IDR may be more effective than DNR in leukemia cells that display the MDR phenotype.

Cell Division↗