Why are clinical problems difficult? General practitioners' opinions concerning 24 clinical problems.

This study was conducted to describe the difficulties perceived by general practitioners concerning 24 common clinical problems and to compare their perceptions with those of faculty members in family medicine. A random sample of 467 general practitioners and all 182 faculty members in family medicine in Quebec were sent one of four open-ended questionnaires, each of which dealt with six clinical problems; 214 general practitioners and 114 faculty members participated. A total of 5111 difficulties were reported; the number reported by each subject varied from 0 to 13 (mean 2.6 [standard deviation 2.09]) per problem. The problems that generated the most difficulties were depression, confusion in the elderly, chronic back pain, loss of autonomy in the elderly and sexually transmitted disease. The most frequent difficulties were with the patient''s noncompliance with treatment, clinical diagnosis, failure of a specific treatment, inadequate health care resources and the physician''s own emotional reactions. The difficulties for each problem were the same in the two groups 70% of the time. Physician''s perceptions of their difficulties can be useful in the planning of initial training and continuing medical education.     

Molecular Study of P-Glycoprotein in Multidrug Resistance Using Surface Plasmon Resonance

P-Glycoprotein is an integral membrane protein which mediates the energy-dependent efflux of various antitumor agents from multidrug-resistant cancer cells. Surface plasmon resonance was used for the detection of P-glycoprotein after solubilization from drug-resistant and drug-sensitive Chinese hamster ovary cells and for the analysis of its interaction with cyclosporin A, a competitive inhibitor of drug efflux. Detection of P-glycoprotein relied on its binding to the monoclonal antibody C219 which was immobilized on a sensor chip. Binding of Zwittergent 3-14-solubilized P-glycoprotein to the antibody was concentration-dependent and reflected the relative abundance of P-glycoprotein in both cell lines. It was abolished when C219 was omitted or replaced by a rabbit anti-mouse IgG antibody and considerably reduced after precipitation of P-glycoprotein with wheat germ agglutinin. Preincubation of solubilized proteins with cyclosporin A increased the amount of protein bound to the antibody by approximately 30%. These results indicate that surface plasmon resonance is well suited to the detection of P-glycoprotein from biological samples and shows promise as a tool for the study of its interaction with different drugs.     

Isolation and Preliminary Characterization of Hydroxamic Acids Formed by Nitrogen-Fixing Azotobacter chroococcum B-8

The free-living diazotroph Azotobacter chroococcum B-8 responded to iron-limited growth conditions by forming hydroxamic acids and an 85,000-dalton outer membrane protein. The Fe(III)-binding hydroxamate compounds stimulated the growth of Arthrobacter flavescens JG-9 and gave a positive Csaky reaction for bound hydroxylamines. The hydroxamates were isolated from liquid cultures by benzyl alcohol extraction and purified by size exclusion chromatography and high-performance liquid chromatography. Four high-performance liquid chromatography fractions, designated A, B, C, and D, had the characteristic hydroxamate absorption maximum at 420 to 423 nm, which did not shift over a pH range from 3.0 to 9.0. Cyclic voltammograms of the iron-hydroxamate complexes exhibited reduction potentials of −0.426 to −0.442 V for fractions A, B, and D and of −0.56 V for fraction C versus the normal hydrogen electrode at pH 8.0. Based on mass spectra, nominal molecular weights of 800 and 844 were assigned to ferrated compounds A and B, respectively. Reductive hydrolysis of compounds A and B in 57% hydriodic acid yielded ornithine as detected by gas chromatography-mass spectrometry. All of these physiological and chemical data strongly support the hypothesis that the high-affinity iron-binding compounds isolated from A. chroococcum B-8 are hydroxamic acids and probably function as siderophores for this diazotroph.     

The utilization of canola and its constituents by lactating dairy cows

Three feeding trials and one nylon bag trial were conducted to determine the effect of supplementing a barley-based control diet with 3.5% canola oil (CO), 22% presscake (CPC) or 9% whole seed (WCS) on feed intake, digestibility, milk yield and composition of lactating dairy cows. Ruminal utilization of canola meal (CM), CPC and WCS was also determined. Increasing the level of fat in the diet had no significant effect on intake of concentrate or digestible energy, or on total tract digestibility of dry matter (DM), crude protein (CP) and acid detergent fibre. Addition of canola in the form of CPC and WCS gave greater energy and ether extract digestibility than C and CO (P < 0.05). Diet had no significant effect on milk production, yield of milk CP, milk lactose + ash, gross energetic efficiency of milk production, milk urea or minerals. Milk fat and 4% fat corrected milk (FCM) yield were similar with the C and CPC diets, and with the CO and WCS diets. But the CO and WCS diets gave less milk fat and FCM than the C diet (P < 0.05). Milk crude protein was higher (P < 0.05) on the WCS diet than on the C, CO and CPC diets, which were similar. Diets WCS, C and CO promoted similar levels of blood urea (BU) but BU levels with CPC and CO were lower than with the C diet (P < 0.05). Ruminal DM and CP disappearance of CM was lower than for WCS and CPC at all incubation times (P < 0.05).