Biomedical subjects

M Bowers

Publications and source records attributed to M Bowers.

At least 19 recordsLinked to original sources

PubMed2000

Multiple factors other than p53 influence colon cancer sensitivity to paclitaxel.

PURPOSE: To determine factors which influence the sensitivity of human colorectal carcinoma cell lines to paclitaxel. METHODS: The paclitaxel sensitivity of ten human colorectal carcinoma cell lines, and a panel of RKO colon carcinoma cell lines, isogenic except for p53 status, were studied. The inhibitory concentrations causing a 50% decrease in growth (IC50) were assayed after 3, 24, and 96 h after paclitaxel exposure. The doubling time (DT) and cell cycle parameters of cells were also measured. The expression of the multidrug resistance glycoprotein-1 (MDR-1), bcl-2 and bax was quantitatively assessed by immunoblotting. RESULTS: Mean IC50 values at 24 and 96 h drug exposure were about 1.5 logs lower than the IC50 values at 3 h, regardless of the p53 status. No difference was found between the IC50 values of wild-type and mutant p53 cells, or among the RKO panel of cells. Correlation analysis showed that: (1) resistance was associated with longer DTs, but this was generally abated by a 96-h exposure; (2) with a 3-h exposure, the combination of MDR, bcl-2 and bax parameters with DT (DT + MDR + bcl-2 bax) best correlated with IC50 values (r = 0.77); (3) with a 96-h exposure, in spite of the generally decreased IC50 values, a combination of MDR-1, bcl-2 and bax parameters (MDR + bcl-2-bax) best correlated with the IC50 values (r = 0.71). CONCLUSIONS: These results suggest that the exposure duration, DT, and expression of MDR-1, bcl-2 and bax each contribute to paclitaxel sensitivity of human colorectal carcinoma cells. In assessing paclitaxel drug resistance, multiple factors should always be considered. There may be a therapeutic window for taxanes in colon cancer by optimizing pharmacokinetics and modulating MDR-1 and bcl-2 resistance factors.

Antineoplastic Agents, Phytogenic↗

PubMed2000

Octreotide in the treatment of gastrointestinal bleeding caused by angiodysplasia in two patients with von Willebrand's disease.

Two cases of von Willebrand's disease and angiodysplasia with intractable gastrointestinal bleeding are presented. Replacement therapy with cryoprecipitate and variable purity von Willebrand factor (VWF) was ineffective, as were other treatments including steroids, immunoglobulin and hormonal replacement. Both patients required massive blood transfusion and product support. The efficacy of somatostatin and an analogue is described. In one patient, we observed a rise in von Willebrand factor activity after octreotide infusion.

Aged↗

PubMed2000

Current trends in the management of heart failure.

Heart failure will continue to present many challenges to health care providers. Research is ongoing to further understand the pathophysiology of this complex disease process. New therapies will be developed that hopefully will have a tremendous impact on the morbidity and mortality of this costly chronic illness. A multidisciplinary approach to treatment offers new opportunities to improve the overall management and quality of life of this population.

Aged↗

PubMed1998

Increased striatal dopamine transmission in schizophrenia: confirmation in a second cohort.

OBJECTIVE: The authors previously observed an increase in striatal dopamine transmission following amphetamine challenge in 15 untreated patients with schizophrenia compared to 15 matched healthy subjects. The purpose of this study was to replicate this finding in a new cohort of schizophrenic patients and healthy subjects. METHOD: Fifteen patients with schizophrenia and 15 healthy subjects matched for age, gender, ethnicity, and parental socioeconomic status were recruited for this study. Patients fulfilled DSM-IV criteria for schizophrenia, had no history of alcohol or substance abuse or dependence, and were neuroleptic free for a minimum of 21 days. Amphetamine-induced dopamine release was assessed by the reduction in dopamine D2 receptor availability induced by an acute amphetamine challenge (0.3 mg/kg, intravenous bolus). Reduction in D2 receptor availability was measured with single photon emission computed tomography and the D2 receptor radiotracer [123I]IBZM. RESULTS: No differences were observed between patients with schizophrenia and the comparison group in D2 receptor availability at baseline. Patients with schizophrenia exhibited a significantly larger reduction in D2 receptor availability following acute amphetamine challenge than the comparison group. In this study, the effect size was smaller than in the first study. Excess dopamine release following amphetamine was associated with transient emergence or worsening of positive symptoms. CONCLUSIONS: In this new cohort of subjects the authors replicated their initial observation of a dysregulation of striatal dopamine release in schizophrenia.

Adult↗

PubMed1998

Assessment of left ventricular compliance during heart preservation.

There is critical need for a greater number of donor hearts for transplantation. The demand can be relieved, in part, by an extension of preservation time. This necessitates new methods of preservation and development of means to assess the functional condition of the preserved heart. We report a heart-preservation system designed for long-term preservation support and discuss issues specifically related to extended heart preservation. This article presents methodology to assess ventricular compliance and to quantify coronary flow distribution during the use of microperfusion preservation. Ventricular adenosine triphosphate (ATP) concentrations are directly related to the immediate post-preservation function: however, direct measurement of ATP is not clinically available. Based on the premise that ventricular compliance relates directly to the ventricular ATP concentrations, we performed sequential ventricular compliance measurements using a simple left ventricular balloon during a 24 h preservation period. A porcine heart model was employed using a continuous, hypothermic, antegrade, microperfusion system for 24 h and measurements were made at specific intervals during the preservation time. The compliance measurements were ascertained by pressure-volume curves using a flaccid balloon inserted into the left ventricle through the mitral valve. In addition, to assess microvascular function during the preservation interval, regional coronary flow measurements were performed using a microsphere technique. We report that after 12 h of preservation there was a twofold reduction in ventricular compliance which decreased further by fivefold at 18 h. In contrast, there was a time-dependent decrease in left ventricular coronary flow, especially with the left-ventricular subendocardial region significantly decreasing by 50% at 12 h. In conclusion, a simple ventricular-compliance balloon provided a direct measurement of ventricular compliance of the preserved heart which may provide an indirect estimate of the ventricular high-energy phosphates of the preserved heart prior to transplantation.

Animals↗

PubMed1998