Patient-provider interaction from the perspectives of type 2 diabetes patients in Muscat,Oman: a qualitative study

Background  

Patients' expectations and perceptions of the medical encounter and interactions are important tools in diabetes management. Some problems regarding the interaction during encounters may be related to a lack of communication skills on the part of either the physician or the patient.     

Acute effects of halothane and enflurane on drug metabolism and protein synthesis in isolated rat hepatocytes

The metabolism of sulphanilamide, antipyrine and paracetamol was studied in the absence and presence of the anaesthetics halothane and enflurane at three different concentrations (0.5, 1.0 and 2.0 mM) in isolated hepatocytes from the rat. Cell viability and protein synthesis were monitored to evaluate toxic effects. A strong concentration related inhibition of antipyrine oxidation (40-70%) and paracetamol conjugation (20-40%) was caused by both halothane and enflurane. Acetylation of sulphanilamide was not inhibited, however, as a slight augmentation was noticed. A significant dose related decrease of cell viability (3-13%) was caused by both anaesthetics. Dose dependent inhibition of the synthesis of stationary cell proteins (15-60%) and the synthesis/secretion of medium proteins (35-85%) was caused by halothane. Similar but slightly less pronounced effects were caused by enflurane. The present findings show that volatile anaesthetics may have general effects as well as different degrees of specific effects on both membrane bound enzyme and soluble enzyme activities.     

Effect of diethylether on the formation of paracetamol sulphate and glucuronide in isolated rat hepatocytes

Diethylether has previously been shown to inhibit several pathways of drug metabolism, including conjugation of paracetamol in isolated rat hepatocytes. Since overall paracetamol conjugation consists of pathways of different subcellular localization (cytosolar sulphation and microsomal glucuronidation) the response of both pathways to diethylether was tested. The elimination of paracetamol (160 mumol/l, initial concentration) and the formation of paracetamol sulphate and glucuronide were measured (high-performance liquid chromatography) in suspensions of isolated rat hepatocytes from fasted and fed animals over 1 h in the absence and presence of diethylether (30 mmol/l). Approximately 90% of the paracetamol elimination was by sulphation and nearly 10% by glucuronidation both in the controls and in the presence of ether. The overall disposition of paracetamol and the formation of sulphate were both reduced by about 50% in the presence of ether compared to the controls while the formation of glucuronide was reduced by 70%. The results were not influenced by the nutritional state of the animals before sacrifice. It is concluded that the inhibitory effect of ether on total paracetamol metabolism was mainly caused by reduced sulphation. Since microsomal glucuronidation was also inhibited by ether, both cytosolar and microsomal enzyme systems were sensitive to diethylether.     

Hamstrings and gastrocnemius co-contraction protects the anterior cruciate ligament against failure: An in vivo study in the rat

An anesthetized rat model was used to study the effects of muscle contraction on the ultimate tensile load and the energy absorption at failure of the anterior cruciate ligament. In both knees, the joint capsule and ligaments, except for the anterior cruciate ligament, were divided, and the menisci were removed with the aid of a stereomicroscope. The cruciate ligament of the right knee was tested in tension until failure by femorotibial distraction during contraction of the hamstrings and calf muscles induced by electrical stimulation of the ischiatic nerve. The cruciate ligament of the left knee, which was loaded to failure with nonstimulated (relaxed) muscles, served as the control. The mean ultimate tensile load during muscle contraction was 86 N compared with 53 N when tested with relaxed muscles (p < 0.001). The energy absorption at failure was 0.41 and 0.19 J during contraction and relaxation, respectively (p < 0.05). This study suggests that previous investigations evaluating the force and energy necessary to rupture the anterior cruciate ligament (with use of a femur-anterior cruciate ligament-tibia complex stripped of all soft tissues and without gastrocnemius-hamstring muscle contractions) are incomplete and probably not representative of the in vivo situation.     

A Reinvestigation of the Usefulness of Breath Analysis in the Determination of Blood Acetaldehyde Concentrations

Human volunteers were given ethanol (0.4 g/kg) either intravenous or per os. They were also given ethanol (0.2 g/kg) intravenous 4 hr after receiving a dose of 50 mg titrated calcium carbimide, an aldehyde dehydrogenase inhibitor. During the first hour after starting the administration of ethanol, ethanol and acetaldehyde concentrations were determined in expired air, blood from the right atrium, arterial blood, and venous blood. In the absence of calcium carbimide treatment, the respective maximal blood acetaldehyde concentrations were (range): 6-30 μM (calculated from breath analysis using a Moodrbreath partition ratio of 190 for acetaldehyde); 0-3.5 μM (right atrium blood); and 0 μM (arterial and venous blood). After calcium carbimide treatment, the maximal blood acetaldehyde concentrations were 10-220 μM (calculated from concentrations in expired air), 38-280 μM (right atrium), 31-250 μM (arterial Wood), and 7-186 μM (venous blood). With aldehyde dehydrogenase inhibition, a clear correlation existed between breath concentrations and blood concentrations. Without this inhibition, no such correlation was found. A clear arterio-venous difference was seen for acetaldehyde concentrations whUe they were artificially elevated by calcium carbimide. Our study suggests that factors other than the equilibration of acetaldehyde between alveolar air and pulmonary blood are of great importance in determining the concentration of acetaldehyde in expired air.     

Covalent binding of 2,4-diaminoanisole and 2,4-diaminotoluene in vivo.

We have studied the activation of 2,4-diaminoanisole (2,4-DAA), a mutagenic hair-dye component, and 2,4-diaminotoluene (2,4-DAT), a hepatocarcinogen, to products which blind covalently to tissue macromolecules. Four hours after a dose of 100 mg/kg ring-labeled 3H-2,4-DAA, 0.30 nmol is found covalently bound per mg liver protein. This amount is increased by 83% after phenobarbital pretreatment, and by 43% after beta-naphthoflavone-pretreatment. Almost the same degree of binding is seen in kidneys. Subcellular fractionation of livers shows that most of the bound material is in the microsomal fraction. Similar levels of covalent protein binding is seen after administering ring-labeled 3H-2,4-DAT. No significant binding to DNA in vitro or in vivo could be demonstrated using 3H-2,4-DAA or 3H-2,4-DAT, whereas 3H-2,4-DAT is found to covalently bind to hepatic RNA.     

p21CDKN1A allows the repair of replication-mediated DNA double-strand breaks induced by topoisomerase I and is inactivated by the checkpoint kinase inhibitor 7-hydroxystaurosporine

This study provides evidence for the importance of p21(CDKN1A) for the repair of replication-mediated DNA double-strand breaks (DSBs) induced by topoisomerase I. We report that defects of p21(CDKN1A) and p53 enhance camptothecin-induced histone H2AX phosphorylation (gammaH2AX), a marker for DNA DSBs. In human colon carcinoma HCT116 cells with wild-type (wt) p53, gammaH2AX reverses after camptothecin removal. By contrast, gammaH2AX increases after camptothecin removal in HCT116 cells deficient for p53 (p53-/-) or p21(CDKN1A) (p21-/-) as the cells reach the late-S and G2 phases. Since p21-/- cells exhibit similar S-phase arrest as wt cells in response to camptothecin and aphidicolin does not abrogate the enhanced gammaH2AX formation in p21-/- cells, we conclude that enhanced gammaH2AX formation in p21-/- cells is not due to re-replication. The cell cycle checkpoint abrogator and Chk1/Chk2 inhibitor 7-hydroxystaurosporine (UCN-01) also increases camptothecin-induced gammaH2AX formation and inhibits camptothecin-induced p21(CDKN1A) upregulation in HCT116 wt cells. TUNEL (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling) assays demonstrate that gammaH2AX formation in late S and G2 cells following CPT treatment corresponds to DNA breaks. However, these breaks are not related to apoptotic DNA fragmentation. We propose that p21(CDKN1A) prevents the collapse of replication forks damaged by stabilized topoisomerase I cleavage complexes.     

Determination of glucocorticoid receptors in leukemic myeloblasts by isoelectric focusing in polyacrylamide gel

We investigated the optimal conditions for measuring glucocorticoid receptor in blast cells from patients with acute nonlymphocytic leukemia. Cytosol receptor measured with isoelectric focusing was saturated after 60 min of incubation at 0 degrees C with 100 nM of either dexamethasone or triamcinolone. Saturation was achieved when cytosol from at least 7 X 10(6) cells was used for incubation. Trypsin treatment of the cytosol resulted in a sharpened peak of receptor focusing at pH 5.6 with no loss of receptor-bound radioactivity. The two physical forms of glucocorticoid receptor were isolated with DEAE cellulose chromatography. They were both found to focus at pH 5.6 during isoelectric focusing.     

Results of hepatic lobectomy for primary epithelial cancer in 31 adults.

Hepatic lobectomy for primary epithelial cancer was performed in 31 adults from 1964 through 1977 in the surgical departments of six Scandinavian hospitals. Twenty-three patients were discharged and had a 2 year survival rate of 62 per cent and a 5 year survival rate of 16 per cent. Alternatives to surgery have not yet emerged. Further progress requires centralization.