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Biomedical subjects

S A Azer

Publications and source records attributed to S A Azer.

18 recordsLinked to original sources
PubMed2001

Rural training and the state of rural health services: effect of rural background on the perception and attitude of first-year medical students at the university of melbourne.

The aim of this project is to investigate the relationship between medical students' background and their perception of the state of rural health services; willingness to undertake internship training or work as a doctor in a rural hospital; expected benefits and disadvantages of training or working as a doctor in a rural hospital; and factors interfering with acceptance of a job as a doctor in rural areas. A questionnaire-based survey was distributed to 100 first-year medical students attending the Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne at the end of semester 1. The response rate was 97%, including 44 males and 53 females. A strong relationship was found between rural background and an intention to undertake internship training in a rural hospital (86% of students from a rural background expressed this desire vs 30% of students from an urban background). Furthermore, all students from a rural background expressed a desire to work as a doctor in a rural hospital after completing postgraduate training. Compared to urban students, students from a rural background showed a more positive attitude towards health services in rural areas including public hospitals ( P = 0.02), private general practice ( P = 0.004), ambulance service ( P = 0.0002) and baby health centres ( P = 0.005). Citizenship or gender was not significantly related to the perception of any of these services. The ranking of factors interfering with acceptance of a job as a doctor in rural areas were different for rural and urban students. Students from rural backgrounds reported spouse/partner needs (76% vs 49%, P = 0.038) and school availability for children (59% vs 30%, P = 0.023) as barriers more frequently than urban students, respectively). On the other hand, urban students rated the following factors higher: personal factors (76% vs 53%, respectively), education opportunities (56% vs 24%), social/cultural facilities (50% vs 41%) and the need for frequent travel (29% vs 12%). None of these interfering factors were significantly different. Urban students were more likely than rural students to report that their views were a result of adverse media reports. In conclusion, students from a rural background were more willing to be trained or to work as doctors in rural areas. This was associated with a greater adverse influence by the media upon students.

Asia, Southeastern↗
PubMed2001

Problem-based learning. A critical review of its educational objectives and the rationale for its use.

Over the past 30 years there has been an increasing interest in curriculum innovation in medical schools in North America, the United Kingdom, Netherlands, and Australia. Since the introduction of problem-based learning at McMaster University in Canada in 1969, several medical schools throughout the world have adopted problem-based learning as the educational and philosophical basis of their curricula. Several studies have shown that problem-based learning is an important educational strategy for integrating the curriculum, motivating the students and helping them to identify their learning issues and set their own learning goals. However, there is a great deal of concern regarding what problem-based learning means and the advantages of problem-based learning over traditional curriculum have not been clearly addressed. In this review, a broad range of the definitions of problem-based learning have been addressed and the rationale for problem-based learning and its educational objectives are discussed.

Australia↗
PubMed2001

Problem-based learning. Challenges, barriers and outcome issues.

Although many recent studies have discussed specific issues related to problem-based learning in medical education, a comprehensive review of the literature on the consequences of its use and the outcomes of curriculum based on problem-based learning have not been accurately looked at. Furthermore, there is no available review that critically evaluates challenges and barriers to the implementation of problem-based learning curriculum in medical schools. The purpose of this part is to highlight the major challenges and barriers reported during curriculum preparation and implementation and to critically evaluate the consequences of problem-based learning introduction and its educational outcomes.

Attitude of Health Personnel↗
PubMed1997

Biochemical assay of serum bile acids: methods and applications.

Immunoassays and bioluminescence assays of bile acids in serum have provided relatively simple and sensitive methods for assessing the concentration of selected sub-groups of bile acids. However, these assays do not provide full data for each of the individual bile acids. The recent development of sensitive techniques such as high-performance liquid chromatography (HPLC) and gas-liquid chromatography-mass spectrometry (GLC-MS) have made possible the separation and quantification of free and conjugated bile acids in biological samples. Several studies have demonstrated the value of individual serum bile acid levels and bile acid ratios when assessing the hepatic function of experimental animals treated with various hepatoxic agents, and in humans with various hepatic disorders. Current data show that individual serum bile acids are more sensitive and specific as early predictors of hepatic injury, and are an accurate independent prognostic indicator. These studies have provided further insight into the various determinants of serum bile acid levels in physiological and pathological conditions affecting the liver. Future studies using these techniques and perhaps monoclonal antibodies, fast atom bombardment-mass spectrometry (FAB-MS) and nuclear magnetic resonance (NMR) for bile acid assays may provide both researcher and clinician with a reliable, sensitive and specific indicator of hepatic injury.

Animals↗
PubMed1996

Sequential changes in serum levels of individual bile acids in patients with chronic cholestatic liver disease.

In order to determine the value of serum bile acids in predicting the course of chronic cholestatic liver diseases, we measured individual serum bile acids serially, using high-performance liquid chromatography, over a 4 year observation period in 12 patients with primary biliary cirrhosis and six patients with primary sclerosing cholangitis. The changes in individual serum bile acids and the ratios thereof, conventional liver tests and Child-Turcotte and Mayo scores were compared between survivors (n = 10) and patients who underwent liver transplantation for (n = 3) or died of the liver disease (n = 5). Patients with a serum total chenodeoxycholic acid concentration at study entry that exceded 15 mumol/L were 10 times more likely to die or need a liver transplant in the following 4 years than those with chenodeoxycholic acid levels < 15 mumol/L (P < 0.05). None of the other biochemical parameters or clinicopathological scores could similarly discriminate between the two groups at entry. Time-dependent analyses for the cholic acid/chenodeoxycholic acid ratio, serum total bilirubin and albumin concentrations and Child-Turcotte and Mayo scores were able to differentiate between primary sclerosing cholangitis patients who died or were transplanted and those who were not, whereas age of the patients and other parameters did not. The taurocholic acid/taurochenodeoxycholic acid ratio fell during progression of primary biliary cirrhosis but rose in temporal relationship with primary sclerosing cholangitis. This differential pattern of change was unique compared with other clinical and laboratory indices. In conclusion, serum chenodeoxycholic acid levels and the cholic acid/chenodeoxycholic acid ratio in both diseases were independent indices that allowed for the prediction of survival or the need for liver transplantation. These indices are worthy of further examination in a larger group of patients as prognostic criteria for chronic cholestatic liver disease and in the assessment of the efficacy of therapeutic interventions, including liver transplantations.

Adult↗
PubMed1996

Current concepts of hepatic uptake, intracellular transport and biliary secretion of bile acids: physiological basis and pathophysiological changes in cholestatic liver dysfunction.

Hepatic sinusoidal uptake of bile acids is mediated by defined carrier proteins against unfavourable concentration and electrical gradients. Putative carrier proteins have been identified using bile acid photoaffinity labels and more recently using immunological probes, such as monoclonal antibodies. At the sinusoidal domain, proteins with molecular weights of 49 and 54 kDa have been shown to be carriers for bile acid transport. The 49 kDa protein has been associated with the Na(+)-dependent uptake of conjugated bile acids, while the 54 kDa carrier has been involved in the Na(+)-independent bile acid uptake process. Within the hepatocyte, cytosolic proteins, such as the glutathione S-transferase (also designated the Y protein), the Y binders and the fatty acid binding proteins, are able to bind bile acids and possibly facilitate their movement to the canalicular domain. At the canalicular domain a 100 kDa carrier protein has been isolated and it has been shown by several laboratories that this particular protein is concerned with canalicular bile acid transport. The system is ATP-dependent and follows Michaelis-Menten kinetics. Interference with bile acid transport has been demonstrated by several chemicals. The mechanisms by which these chemicals inhibit bile acid transport may explain the apparent cholestatic properties observed in patients and experimental animals treated with these agents. Several studies have shown that Na+/K(+)-ATPase activity is markedly decreased in cholestasis induced by ethinyloestradiol, taurolithocholate and chlorpromazine. However, other types of interference have been described and the cholestatic effects may be the result of several mechanisms. Cholestasis is associated with several adaptive changes that may be responsible for the accumulation of bile acids and other cholephilic compounds in the blood of these patients. It may be speculated that the nature of these changes is to protect liver parenchymal cells from an accumulation of bile acids to toxic levels. However, more detailed quantitative experiments are necessary to answer questions with regard to the significance of these changes and the effect of various hepatobiliary disorders in modifying these mechanisms. It is expected that the mechanisms by which bile acid transport is regulated and efforts to understand the molecular basis for these processes will be among the areas of future research.

Animals↗
PubMed1995

Mechanism of ketoconazole-induced elevation of individual serum bile acids in the rat: relationship to the effect of ketoconazole on bile acid uptake by isolated hepatocytes.

Ketoconazole, an imidazole derivative, has been implicated in a number of hepatic dysfunctions. The aim of the present study was to determine the effect of in vivo treatment of rats with ketoconazole on individual serum bile acid levels and the in vitro effects of ketoconazole on the hepatocellular uptake of two bile acids and two other model substrates transported by liver cells. Male Sprague-Dawley rats were treated i.p. with a single injection of ketoconazole of 25 mg/kg (n = 4) or 50 mg/kg (n = 4); the control group (n = 4) received the vehicle only at a dose of 1 ml/kg. Blood samples were collected at 4 hr after dosing. With high-performance liquid chromatography, the serum was assayed for individual serum bile acids. At the higher dose, ketoconazole produced a significant increase in serum levels of cholic acid, taurocholic acid, chenodeoxycholic acid, glycocholic acid, glycochenodeoxycholic acid, glycodeoxycholic acid, deoxycholic acid and taurochenodeoxycholic acid compared with the control group (P < .05). Cholic acid, taurocholic acid and chenodeoxycholic acid levels were significantly raised in rats treated with the lower dose. In vitro, ketoconazole strongly inhibited the hepatocellular uptake of [14C]cholic acid, [14C]taurocholic acid and [3H]ouabain but not [14C]2-aminoisobutyric acid, which indicated that the effect is relatively specific. The kinetics of inhibition were competitive and the inhibition constants for taurocholate and ouabain were 6 and 1 microM, respectively. Ketoconazole inhibited by both Na(+)-dependent taurocholate uptake and stimulated bile acid countertransport of preloaded hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Daily determination of individual serum bile acids allows early detection of hepatic allograft dysfunction.

Acute graft rejection is still a major cause of morbidity after orthotopic liver transplantation, and its diagnosis necessitates an invasive liver biopsy. Our aim has been to determine whether changes in individual serum bile acid levels after engraftment are sensitive, specific and reliable indicators of graft function and whether these changes can antedate other biochemical indicators of hepatic allograft rejection. Individual bile acids in 200 serum samples taken serially from eight adult liver transplant patients were measured. Patients with biopsy-confirmed graft dysfunction due to rejection or nonrejection causes (n = 6 episodes) had significantly higher serum concentrations of glycocholate plus glycochenodeoxycholate and taurocholate/taurochenodeoxycholate ratios than did noncomplicated grafts (n = 3). These changes antedated any other conventional biochemical parameters by at least 48 hr and were 100% sensitive and specific. None of the conventional liver function tests could match this. Acute rejection episodes (n = 3) were then compared with nonrejection causes of graft dysfunction (n = 3). In acute rejection we noted a significant increase in the concentration of glycodeoxycholate plus deoxycholate and a significant decrease in the cholate/chenodeoxycholate ratio compared with that in nonrejection graft malfunction. Both of these changes antedated any other biochemical parameters by 24 hr. In conclusion, individual serum bile acid assays, after orthotopic liver transplantation, can detect graft dysfunction resulting from any cause at an earlier time than routine biochemical tests, and they are sensitive, specific and reliable for early detection of graft dysfunction. In addition, acute rejection can be distinguished from other causes of graft dysfunction.

Adolescent↗
PubMed1994

Differential effects of cyclosporin A on transport of bile acids by rat hepatocytes: relationship to individual serum bile acid levels.

Cyclosporin A treatment has been reported to induce hepatotoxicity marked by a rise in total serum bile acid and total bilirubin. The mechanism of cyclosporin A-induced hepatotoxicity seems to be related to interference with hepatocellular transport of these substrates although this remains to be fully substantiated. The purpose of this study was to investigate whether the hepatocellular uptake of the different bile acids, in the presence of cyclosporin A, is consistent with the changes in their respective individual serum bile acid concentrations. High-performance liquid chromatography has been used to assay individual serum bile acids in cyclosporin A-treated rats at doses of 0.1, 1, and 10 mg/kg/day for 4 days. Control rats were treated with Cremophor (1 ml/kg/day). At the higher doses, cyclosporin A produced a significant increase in levels of cholic acid, taurocholic acid, chenodeoxycholic acid, and deoxycholic acid compared with controls. Serum glycocholate was unaffected even at the highest dose. Inhibition of initial rate of uptake and accumulation of [14C]cholic acid, [14C]chenodeoxycholic acid, and [14C]deoxycholic acid by isolated rat hepatocytes was consistent with the changes in their respective serum bile acids. Coincubation of rat hepatocytes with unlabeled cholic acid (100 microM), the major serum bile acid in cyclosporin A-treated rats, showed a further inhibitory effect on [14C]cholic acid and [14C]deoxycholic acid accumulation. The initial rate of uptake of [14C]glycocholate was also inhibited. However, accumulation of glycocholic acid did not show significant changes at the longer incubation times (2-30 min). In addition, coincubation of rat hepatocytes with unlabeled cholic acid (100 microM) plus cyclosporin A did not induce any inhibition of glycocholate accumulation. Together, these differences provide an explanation for the unchanged serum levels of glycocholate. In conclusion, the changes in individual serum bile acids in cyclosporin A-treated rats are consistent with the effect of this drug on their hepatocellular accumulation.

Animals↗
PubMed1993

Differential effects of cyclosporin A on the transport of bile acids by human hepatocytes.

Cyclosporin A (CsA) treatment has been reported to cause rises in serum bile acids both in humans and rats. It has also been shown to suppress bile flow in situ in rats and inhibit the transport of bile salts by rat hepatocytes. The purpose of this study was to examine the influence of CsA on uptake of radiolabelled cholate (CA), glycocholate (GC) and taurocholate (TC) by isolated human hepatocytes. CsA did not significantly change Vmax for CA uptake [0.23 +/- 0.01 vs 0.25 +/- 0.02 nmol/mg protein/min for control and CsA (10 microM), respectively], but significantly increased Km (37 +/- 2 vs 86 +/- 8 microM). Similarly, Vmax for TC uptake was not affected (0.51 +/- 0.02 vs 0.67 +/- 0.05 nmol/mg protein/min) while Km was significantly increased [46 +/- 3 vs 109 +/- 11 microM for control and CsA (10 microM), respectively]. On the other hand, neither Vmax nor Km for GC uptake was affected by CsA. The data indicate a competitive pattern of inhibition induced by CsA on CA and TC uptake. Furthermore, CsA was found to cause a dose-related inhibition of accumulation of both cholate and taurocholate, but not GC accumulation. None of the concentrations of CsA showed a significant effect on the integrity of the human hepatocytes as assessed by ALT (alanine aminotransferase), AST (aspartate aminotransferase) and LDH (lactate dehydrogenase) release. The findings, in human hepatocytes, are generally consistent with the observations reported from rodent studies. They strongly support the contention that serum bile acid increases in CsA-treated patients are due to interference with the hepatocellular transport and accumulation of particular bile acids.

Adolescent↗
PubMed1993

Selectivity and sensitivity of changes in serum bile acids during induction of cirrhosis in rats.

Because some patients with cirrhosis have serum transaminase levels within the normal range, a prospective study was undertaken to determine whether the concentration of individual serum bile acids would be a sensitive indicator of development of cirrhosis. The choline-deficient rat has been used as a model for study of these changes. Using high-performance liquid chromatography, we measured the concentrations of individual serum bile acids at 3, 6, 10, 20 and 30 wk of dietary intake. Serum levels of total glycine- and taurine-conjugated bile acids were elevated at all stages tested as compared with levels in control groups (choline supplemented). Similarly, unconjugated bile acids and, particularly, cholic acid showed significantly higher levels at all stages except with the occurrence of cirrhosis at 30 wk, at which time there was a significantly lower level for unconjugated bile acids (0.48 +/- 0.11 vs. 1.40 +/- 0.36 in controls) and for cholic acid (0.17 +/- 0.05 vs. 0.91 +/- 0.39 in controls). The ratio of serum cholic acid to serum chenodeoxycholic acid changed in temporal relationship to progression in the histological lesions in livers of these rats. The ratio was at its highest at 78 +/- 3 at 3 wk (no histological change) and decreased with increasing time and changes in histological appearance until 30 wk, at which time it was down to 1.6 +/- 0.6. The routinely used markers of liver injury (serum ALT, alkaline phosphatase and bilirubin), however, did not match the progression of hepatic histological changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗
PubMedDate not supplied

Hepatoprotection in ethinylestradiol-treated rats is provided by tauroursodeoxycholic acid, but not by ursodeoxycholic acid.

Ursodeoxycholic acid (UDCA) and tauroursodeoxycholic acid (TUDCA) have been suggested as potential treatments for drug-induced cholestasis. It was therefore decided to study the effects of administration of UDCA or TUDCA on individual serum bile acid concentration, conventional liver tests and associated hepatic ultrastructural changes in ethinylestradiol-treated (EE) rats mg/kg per day). Control rats were treated s.c. with propylene glycol. EE-treated rats were randomly assigned to receive daily i.p. injections of placebo, TUDCA or UDCA. Four rats in each group were treated for 4 consecutive days, and a second four for 14 days. After 4 days of treatment, the serum levels of cholic acid and taurocholic acid were significantly increased in EE-treated rats. None of the conventional liver tests were significantly different among the four groups. After 14 days of treatment the serum levels of cholic acid, chenodeoxycholic acid, glycocholic acid, glycochenodeoxycholic acid, taurocholic acid, taurochenodeoxycholic acid, bilirubin, alkaline phosphatase and gamma glutamyltransferase were significantly raised in EE and EE plus UDCA treated rats. EE plus TUDCA treated rats, however, had no significant changes in these individual serum bile acids or conventional liver tests. The ultrastructure of livers from EE plus TUDCA treated rats was similar to those of controls. On the other hand, EE and EE plus UDCA rats both showed a significant reduction in sinusoidal microvilli. These results show that treatment of rats for 4 days with EE induces significant rises in the serum concentrations of two individual bile acids and that TUDCA protects against this.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Retrosternal pain.

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Angina, Unstable↗