New potent verapamil derivatives that reverse multidrug resistance in human renal carcinoma cells and in transgenic mice expressing the human MDR1 gene.

Multidrug resistance in human renal cell carcinoma is mainly caused by expression of the MDR1 gene and is characterized by a broad spectrum cross resistance to many natural product chemotherapeutic agents. This resistance can be overcome by applying chemosensitizers which inhibit the function of the MDR1 gene product P-glycoprotein. The development of new reversing agents with fewer side effects and a higher potency in modifying resistance is a high priority of research on drug resistance. We have evaluated four new verapamil derivatives on 21 primary human renal cell carcinomas in vitro, and also tested them in an MDR-transgenic mice model. These mice express the human MDR1 gene in their bone marrow cells and measurement of their white blood counts provides a simple, rapid and reliable system to screen for the potency of MDR-reversing agents in vivo. We demonstrate here that all four drugs are effective in reversing multidrug resistance in primary cultures of human renal cell carcinomas when used in combination with vinblastine chemotherapy, and to a lesser extent with doxorubicin or daunomycin chemotherapy. Our in vivo data indicate that two of these reversing agents display low toxicity at high concentrations and are more effective at low, clinically achievable concentrations, than the other two drugs and R-verapamil. These results make the two new drugs attractive candidates to be taken into clinical trials.     

Dietitians' perceptions about and personal nutrition practices for cancer risk reduction

This study was undertaken to examine the beliefs and practices of dietitians in relation to cancer risk reduction through nutrition. Respondents to the national survey (N=384, 70 percent) were similar in demographic, educational, and professional characteristics to the American Dietetic Association census data. They reported a strong preventive health orientation: mean performance on 10 preventive health behaviors was 77.5 on a 100 point scale. Half (53 percent) believed cancer would be serious if they developed it, 47 percent believed it was not likely that they would. About 20 percent of the respondents felt that the role of nutrition in cancer etiology was unclear. Dietitians believed strong research support existed for increasing whole grains, fruits and vegetables, and fiber to reduce cancer risk but that little evidence supported use of dietary supplements. Dietitians regularly practiced 75 percent of nutrition recommendations they believed to be effective in reducing cancer risk. Beliefs about the effectiveness of a recommendation accounted for the largest percentage of variance on nutritional practices. While dietitians reported many preventive health practices, including following nutrition recommendations, they seemed to be doing so for reasons other than preventing cancer.Nancie S. Merlino is Assistant Professor, Nutrition and Food Science, Wayne State University, Detroit, MI 48202 and James H. Price, Professor of Health Promotion, Department of Health Promotion, University of Toledo, Toledo, OH 43606.Acknowledgement goes to Stephen Jurs, PhD; Fredrick Andres, PhD; and John Kish, PhD for assistance in design and analysis.     

Effect of obesity on left ventricular function studied by radionuclide angiocardiography

Several studies have shown a significant association of obesity with cardiovascular morbidity and mortality. The present study was carried out to investigate central and systemic haemodynamics in overweight and moderate obese, but otherwise healthy subjects, and in a lean control group to determine whether obesity can influence left ventricular performance per se. In this study an attempt has been made to eliminate misleading factors, such as diabetes, lipid abnormalities and hypertension. A total of 67 subjects, 44 with overweight or moderate obesity and 23 lean healthy subjects, were included. Patients were divided into three groups according to BMI levels and Garrow's criteria as follows: lean control group (BMI less than 25 kg/m2); overweight (BMI from 25 to 30 kg/m2); moderate obese (BMI greater than 30 less than 40 kg/m2). Overweight and moderate obese subjects were further subgrouped according to duration of obesity (DO) in subgroup A (DO less than 98 months) and in subgroup B (DO greater than 98 months). Haemodynamic assessment was performed using first pass radionuclide angiocardiography. When compared with lean subjects, overweight and moderate obese subjects were characterized by a significant increase in cardiac output (CO), stroke volume (SV), end diastolic volume (EDV), end systolic volume (ESV), total blood volume (TBV) and total plasma volume (TPV) and by a significant decrease in left ventricular ejection fraction (EF); some of these changes appeared to be related to the degree of obesity. In overweight and moderate obese subjects, total peripheral resistance (TPR) was lower than in lean controls, but this difference was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of naloxone on the preoperative gastric volume and pH

The effect of 4 mg oral naloxone on preoperative gastric volume and pH of gastric aspirate was studied in a double-blind, randomized study. Twenty patients received 10 ml of naloxone (4 mg) mixed with 10 ml of orange juice, and 20 patients received 10 ml of isotonic saline mixed with 10 ml of orange juice, 2 h before surgery. Gastric content was obtained immediately after intubation of the trachea. No significant difference in gastric volume and pH of gastric aspirate was found between the two groups. It is concluded that naloxone does not affect gastric emptying and gastric acid secretion to a degree great enough to protect against aspiration of gastric contents into the lungs.     

The lateral arm free flap in lower extremity reconstruction

Reconstruction of skin defects of the distal third of the leg and foot is often a difficult task. Shape, resistance to shearing stresses in the weight-bearing surface and sensibility are the main features that have to be restored. For coverage of this region, the authors have used, in selected patients, the lateral arm flap (LAF) since 1994. This flap is thin, easy to dissect and has the possibility to be innervated through the posterior cutaneous nerve of the arm. Fourteen cases are presented. The drawbacks of this flap are the loss of sensibility in the forearm (partially transient) and the scar on the arm, which can be rather unsightly in young ladies and when big flaps are harvested skin graft is needed.