Modernising physician resource planning: a national interactive web platform for Canadian medical trainees.

BACKGROUND: Healthcare systems rely heavily upon human resources to ensure high-quality access to care for the general population. With significant health worker shortages predicted worldwide in the coming decades, maximizing the current workforce by means of a physician resource planning (PRP) strategy that ensures the right number, mix, and distribution of physicians to meet population needs is warranted. In Canada, there is an insufficient number of primary care providers, and disproportionately low numbers of specialist physicians in rural compared to urban regions. Currently, Canadian medical students are not effectively included in PRP strategy and lack the required information for career orientation to help rebalance the population's workforce needs. This paper present the Health Human Resource (HHR) Platform, a comprehensive web tool that includes relevant workforce data to empower medical students in choosing a discipline based on both personal interests and social accountability. RESULTS: Physician workforce data, comments from Canadian residency program directors, and career planning resources were collected by the Canadian Federation of Medical Student's (CFMS) HHR Task Force. This information was consolidated to create a national interactive platform that uses a map, comparison table, and trend graphs to illustrate over 500,000 unique data points from 37 datasets, including specific information and resources spanning 62 medical specialties from 2015 onwards. There was a 24.6% response rate for program director comments. During the first 4 months of the HHR Platform launch, there were 2434 different users, of which 985 were returning, with an average of 20.0 users per day spending on average 3 min on the platform. CONCLUSIONS: The HHR Platform constitutes a national approach to PRP informing medical students on the mix and distribution of physicians needed to meet the future healthcare demands of the Canadian population.

The effect of sevoflurane and desflurane on markers of oxidative status in erythrocyte.

The aim of our study was to evaluate the markers of oxidative status of erythrocyte during general anesthesia and compare the markers of oxidative status of erythrocyte in both sevoflurane and desflurane. Venous blood samples of patients were collected the following time intervals; initial time (IT) and first hour (1st h), first (1st day) and third days (3rd day) after anesthesia (sevoflurane and Desflurane). The levels of magnesium (Mg), zinc (Zn) as a cofactor of these enzymes, malondialdehyde (MDA) and the activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) enzymes were also determined. No significant changes were observed in these measurements when the patients were exposed to desflurane anesthesia. On the other hand, the levels of Zn on erythrocytes were significantly increased at 1st hour and 1st and 3rd days compared to initial time in sevoflurane group (p < 0.01, p < 0.01, and p < 0.05, respectively). The activity of GSH-Px was significantly increased (p = 0.05) while the activity of SOD was significantly decreased (p < 0.01) at 1st hour after administration of sevoflurane compared to the initial time. There were no changes on the levels of Mg and MDA. Our results showed that sevoflurane has more impacts on the antioxidant status of erythrocytes than desflurane.

High-dose testosterone and dehydroepiandrosterone induce cardiotoxicity in rats: Assessment of echocardiographic, morphologic, and oxidative stress parameters.

The aim of this study is to assess cardiotoxic effect of testosterone (TES) and dehydroepiandrosterone (DHEA) in Sprague Dawley rats. We compared the impact of subacute (14 days) and subchronic (90 days) administration of suprapharmacologic doses of TES and DHEA on body weight, locomotor activity, muscle strength, echocardiographic parameters, heart histopathology, and oxidative stress markers with the control group. Testosterone (10, 30, and 100 mg/100 g body weight) and DHEA (10 mg/100 g body weight) administration decreased the body weights and locomotor activity (p < 0.05), and the combination of both increased muscle strength (p < 0.05) in rats. In our histopathological evaluation, misshapen cell nuclei, disorganized myocardial fibers, and leukocytic infiltrates were observed in high-dose TES (100 mg/100 g)-treated rats, especially on day 14. On day 90, mild changes such as misshapen cell nuclei, disorganized myocardial fibers, and leukocytic infiltrates were observed in TES and DHEA-treated groups. According to our echocardiographic study on day 14 and day 90, TES, especially at high doses, induced increase in left ventricular posterior wall diameter and ejection fraction (p < 0.05). In this study, blood oxidative stress marker malondialdehyde was increased slightly but not significantly in TES and DHEA groups. On the other hand, antioxidant enzymes such as SOD and glutathione peroxidase (GSH-Px) levels were slightly but not significantly increased in TES and DHEA groups. These data demonstrate that the potential risk to cardiac health due to exogenous androgen use may be related to oxidative stress in rats.

Polymorphic debrisoquin metabolism in a Turkish population.

Debrisoquin hydroxylation polymorphism was studied in 326 unrelated healthy Turkish volunteers. Debrisoquin sulfate (10 mg) was administered to subjects, and debrisoquin and 4-hydroxydebrisoquin were determined in the 0- to 8-hour urine samples. Debrisoquin oxidation was polymorphic, with 11 subjects (3.37%; 95% confidence interval, 1.69% to 6.07%) phenotyped as poor metabolizers. The metabolic ratio between debrisoquin and 4-hydroxydebrisoquin in 8-hour urine samples ranged from 0.02 in extensive metabolizers to 263.8 in poor metabolizers. The proportion of poor metabolizers was found to be in the range observed in the other white populations studied.

Investigation of antioxidant enzymes in children with autistic disorder.

Impaired antioxidant mechanisms are unable to inactivate free radicals that may induce a number of pathophysiological processes and result in cell injury. Thus, any abnormality in antioxidant defence systems could affect neurodevelopmental processes and could have an important role in the etiology of autistic disorder. The plasma levels of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), and erythrocyte levels of GSH-Px were investigated in 45 autistic children and compared with 41 normal controls. Levels of erythrocyte SOD, erythrocyte and plasma GSH-Px were assayed spectrophotometrically. Activities of erythrocyte SOD, erythrocyte and plasma GSH-Px in autistic children were significantly lower than normals. These results indicate that autistic children have low levels of activity of blood antioxidant enzyme systems; if similar abnormalities are present in brain, free radical accumulation could damage brain tissue.

Lipid peroxidation and antioxidant system in the blood of patients with Hodgkin's disease.

OBJECTIVES: The purpose of this study was to measure the extent of lipid peroxidation and the status of antioxidants in patients with Hodgkin's disease. DESIGN AND METHODS: Glutathione peroxidase (GPX) and superoxide dismutase (SOD) activities, and malondialdehyde (MDA), selenium, zinc and copper content have been measured in 20 patients with Hodgkin's disease and 30 age-matched controls. RESULTS: Significantly higher concentrations of MDA in plasma as well as in erythrocytes were found compared to the control group. In both plasma and erythrocytes, GPX activity, selenium and zinc levels were significantly lower in patients than in controls. However, SOD activity in erythrocytes and copper levels in both plasma and erythrocytes were significantly higher in patients. CONCLUSION: We conclude that the antioxidant system is impaired in Hodgkin's disease due to the abnormal metabolism of trace elements and antioxidant enzymes.

Oxidative stress and nitric oxide related parameters in type II diabetes mellitus: effects of glycemic control.

OBJECTIVES: The aim of this study is to investigate the status of oxidative stress and nitric oxide related parameters in type II diabetes mellitus (DM) patients in which heart disease, atherosclerosis, retinopathy, and nephropathy commonly occur, and also to determine the effect of glycemic control on these parameters. DESIGN AND METHODS: Erythrocyte copper zinc-superoxide dismutase (CuZn-SOD), erythrocyte and plasma selenium dependent glutathione peroxidase (Se-GPx), erythrocyte catalase (CAT) activities, erythrocyte and plasma thiobarbituric acid reactive substances (TBARS) levels; nitrite/nitrate (NO(2)(-)/NO(3)(-)), cyclic guanosine monophosphate (cGMP) and nitrotyrosine levels in plasma of type II DM patients were measured. RESULTS: Erythrocyte CuZn-SOD activities in type II DM were significantly higher than those of the control subjects (p < 0.05). TBARS levels in type II DM were significantly higher than the control subjects (p < 0.001). Plasma NO(2)(-)/NO(3)(-) levels in type II DM patients both during poor glycemic control and after three months of oral antidiabetic treatment were significantly higher than those of the control subjects (p < 0.001). Plasma cGMP levels in type II DM patients during poor glycemic control were significantly lower than those of control subjects (p < 0.001). CONCLUSION: These results indicate that oxidative status and nitric oxide metabolism are affected in type II DM patients. We found high CuZn-SOD activity in type II DM patients. This increased activity could not protect the patients against the reactive oxygen species (ROS), since lipid peroxidation (defined by erythrocyte and plasma TBARS levels) still occurs in DM patients. After the therapy with oral antidiabetic agents for three months, erythrocyte SE-GPx and CAT activities were found to be decreased below the control values. Our results suggested that the low cGMP levels in the study may be a good marker of endothelium dysfunction in DM.

Oxidative stress status in adults with nephrotic syndrome.

BACKGROUND: Excessive generation of reactive oxygen species is one of the incriminated mechanisms in the pathogenesis of progressive renal injury. The role of oxidant stress in acute and chronic glomerular diseases has been investigated through experimental and clinical studies. SUBJECTS, MATERIALS AND METHODS: In the present study, oxidative stress status in adult nephrotic patients was studied by determining plasma selenium levels, erythrocyte and plasma glutathione peroxidase (GSH-Px) activities, erythrocyte superoxide dismutase (Cu-Zn-SOD) activity, erythrocyte and plasma levels of malondialdehyde (MDA). RESULTS: Twenty adult nephrotic syndrome patients included into the study had lower activities of erythrocyte (17.17 +/- 2.29 U/gHb) and plasma (153.76 +/- 20.12 U/l) GSH-Px activities when compared the controls ( 27.05 +/- 7.30 U/gHb and 308.89 +/- 55.04 U/l for erythrocyte and plasma GSH-Px activities, respectively). They also had lower erythrocyte Cu-Zn-SOD activity (1896.30 +/-94.31 U/gHb) than that of the controls (2506.17 +/- 461.08 U/gHb). Erythrocyte (483.40 +/- 37.45 nmol/gHb in patients vs 210.35 +/- 55.55 nmol/gHb in controls) and plasma (4.84 +/- 0.65 nmol/ml in patients vs 2.03 +/- 0.41 nmol/ml in controls) levels of MDA were higher in patients. Plasma selenium levels of the patients (48.0 +/- 7.28 ng/ml) were lower than that of the controls (69.25 +/-5.80 ng/ml). CONCLUSION: In conclusion, these results obtained in adult nephrotic syndrome patients support the previous data indicating an abnormality in antioxidative system of nephrotic patients.

Trace element (Al, Se, Zn, Cu) levels in serum, urine and tissues of burn patients.

Trace elements are known to play many important roles in humans. It has also been shown that some of these elements are essential in wound healing. In this study, aluminium, copper, zinc and selenium levels were determined in serum, urine and tissue samples of burned patients and the relationships between wound healing and trace elements were evaluated. Trace element levels were determined using atomic absorption spectrophotometry. During 20 days' treatment, a significant rise in aluminium levels was determined in serum, urine and tissue samples of patients. After day 5 of treatment, copper levels increased significantly only in urine samples. Zinc levels decreased in serum and tissue samples. However, zinc gave high values in urine within the first week then returned to the initial value. There was a significant decrease in zinc in serum and tissue samples taken from burned patients during treatment. Urine selenium levels showed a significant rise within the first 15 days.

Plasma glutathione peroxidase activity and selenium levels of newborns with jaundice.

The plasma glutathione peroxidase (GSH-Px) and selenium (Se) levels were determined in 31 newborns affected by jaundice (NWJ). The GSH-Px levels of both full-term and premature newborns exhibiting jaundice and having a birthweight lower than 2000 g were significantly low (p < 0.05) when compared to controls. No significant differences were found in the corresponding Se levels, which were similar in all groups and independent of the pregnancy period and birthweight.

Antioxidative metabolism in Down syndrome.

Down syndrome is the most common cause of mental retardation, affecting 1 in 700-800 liveborn infants. Although numerous biochemical abnormalities accompanying the syndrome have not yet been completely clarified, the antioxidant defense system enzymes have shown to be altered due to increased gene dosage on chromosome 21 and overproduction of superoxide dismutase (SOD-1 or Cu/Zn SOD). The purpose of this study was to investigate the activities of SOD-1 and glutathione peroxidase (GSH-Px) enzymes and the levels of their cofactors zinc (Zn), copper (Cu) and selenium (Se) in plasma of 20 Down syndrome patients. In comparison with age and sex-matched controls (n = 15), plasma GSH-Px, SOD, and Cu levels were significantly decreased in the patient group, but Zn and Se concentrations remained unchanged.

Serum selenium and glutathione-peroxidase activities and their interaction with toxic metals in dialysis and renal transplantation patients.

Selenium, aluminum, cadmium, and magnesium concentrations and glutathione-peroxidase activities in sera of 35 healthy individuals, 30 renal transplants, and 30 hemodialysis patients were measured. Serum selenium, aluminum, and cadmium concentrations in both groups of patients were higher than the controls (p less than 0.001), whereas the serum glutathione-peroxidase levels were lower (p less than 0.001). According to our results, it can be concluded that the patients receiving hemodialysis are subjected to more toxic elements than the transplantation patients. These findings imply that dietary selenium supplement may be suggested in renal failure for the detoxification of elements, such as cadmium and mercury. The essential trace element selenium takes part not only in the direct protection of endothelial cells against the accumulation of aggressive oxygen species, but also in the prevention of the toxic effects of cadmium or in the modulation of the active calcium transport.

Selenium and Behçet's disease.

Behçet's disease is an inflammatory disorder of unknown etiology, characterized by recurrent oral and genital aphthous ulcers, ocular inflammation, and skin lesions of erythema nodosum and acneiform eruptions. Selenium (Se) affects all components of the immune system, i.e., the development and expression of nonspecific, humoral, and cell-mediated responses. In general, a deficiency in Se appears to result in immunosuppression, whereas supplementation with low doses of Se appears to result in augmentation and/or restoration of immunologic functions. In this study, the distribution of Se and IgG, IgM in serum were compared in samples from healthy adult control and Behçet's disease patients. The serum Se levels were measured by AA-30-40 Varian Spectra, and immunoglobulins were measured by immunodiffusion technique. The mean (SD) serum Se level of 54.24 +/- 8.06 ng/mL among Behçet's disease subjects was significantly different (P less than 0.01) from that in the control subjects (90.01 +/- 9.94 ng/mL). We also measured IgG and IgM as 10.01 +/- 2.74 mg/mL and 1.26 +/- 0.29 mg/mL, respectively for patients, and 15.08 +/- 4.73 mg/mL and 1.58 +/- 0.43 mg/mL for controls. The mean values of IgG and IgM for patients were significantly (P less than 0.05) different from the values of controls. It seems, therefore, that a deficiency in selenium impedes the humoral immune response.

Effects of statins on oxidative stress.

Free oxygen radicals and insufficient antioxidant enzymes have been implicated in the pathogenesis of hypercholesterolemia (HC). Trace elements function as cofactors in antioxidant enzymes. Antioxidant system and trace elements were investigated in many different studies including HC, but these subjects have not been investigated as a whole in these patients. The aim of the present study was to investigate the antioxidative system and trace elements in hypercholesterolemic patients given fluvastatin therapy. We examined malondialdehyde (MDA), copper zinc-superoxide dismutase (CuZn-SOD), and glutathione peroxidase (GSH-Px) activities together with copper (Cu), iron (Fe), and zinc (Zn) levels in erythrocytes of 35 patients with HC and 27 healthy control subjects. It was found that in patients with HC, erythrocyte MDA was significantly higher than those of controls and erythrocyte CuZn-SOD and GSH-Px activities were significantly lower in patients with HC. Erythrocyte iron levels were significantly higher than those of controls, and erythrocyte copper and zinc levels were significantly lower in patients with HC. Plasma lipid levels and the oxidative state were analyzed in statin-treatment groups given fluvastatin therapy before and after a 3-mo treatment period. In conclusion, we found that fluvastatin has significant antioxidant properties and these effects might be very important in managing dyslipidemia by improving endothelial function.

Omission of the deconjugation step in urine analysis and the unaltered outcome of CYP2D6 phenotyping with dextromethorphan.

The present study was aimed at determining whether the deconjugation step in chemical analysis could be omitted without altering the outcome of phenotyping CYP2D6 with dextromethorphan. This drug and its metabolite, dextrorphan, were assayed by high-performance liquid chromatography (HPLC) in urine. Urinary levels of dextromethorphan and dextrorphan with and without enzymatic (beta-glucuronidase) treatment of urine and the metabolic ratios for dextromethorphan were determined in 45 subjects. Although the enzymatic treatment did not alter the urinary concentration of dextromethorphan in both phenotypes, it increased the urinary concentration of dextrorphan in both poor and extensive metabolizers by 3.7- and 12.8-fold, respectively. A urinary unconjugated dextromethorphan/unconjugated dextrorphan metabolic ratio of 2.00 and a total dextromethorphan/total dextrorphan metabolic ratio of 0.30, respectively, identified three poor metabolizers. Enzymatic treatment decreased the urinary antimode value. Moreover, the urinary metabolic ratio based on unconjugated dextrorphan and dextromethorphan correlated well with that based on assay of total dextrorphan and dextromethorphan (rs = 0.9458, P < 0.001). The results show that urinary analysis of dextrorphan and dextromethorphan omitting the enzymatic deconjugation step is a fast, reliable and sensitive method and could be used for studying CYP2D6 type genetic polymorphism in man.

Metabolic ratios of four probes of CYP2D6 in Turkish subjects: a cross-over study.

The relationships among the metabolic ratios for the standard probe drugs of CYP2D6 activity, such as debrisoquine, sparteine, metoprolol and dextromethorphan, were studied in 32 Turkish subjects. All subjects were randomly selected according to their phenotypes from a group of 111 Turkish subjects whose oxidation status had been tested for debrisoquine previously. All subjects were given a 10 mg debrisoquine tablet, a 100 mg sparteine tablet, a 100 mg. metoprolol tablet and a 20 mg dextromethorphan capsule orally with a wash-out period of at least 1 week between each probe administration. Metabolic ratios were calculated as percentage of dose excreted as parent drug/percentage of dose excreted as its hydroxymetabolite of parent drug in 0-8 h urine. Three poor metabolisers (PM) of debrisoquine were identified. They were also PMs of the other test probes and no misclassification by the 4 phenotyping methods was observed. All six correlations among the metabolic ratios of the 4 probe drugs assessed by Spearman's rank test were highly significant (P < 0.001). The present findings indicate that the oxidative metabolism of debrisoquine, sparteine, metoprolol and dextromethorphan is catalysed by the same cytochrome P450 in the Turkish subjects.

Prevalence of preventable ear disorders in over 15,000 schoolchildren in northern India.

BACKGROUND: There is a considerable scarcity of reliable population-based data on the prevalence of preventable ear disorders in developing countries. This study was conducted to determine the prevalence of preventable ear disorders in primary school children (aged 5 to 12 years) in northern India. METHOD: A pro forma questionnaire was used to screen 15 718 primary school children in New Delhi for ear disorders. Ear examinations were conducted using otoscopy and impedance audiometry. RESULTS: Impacted cerumen was prevalent in 7.93 per cent of schoolchildren, 4.79 per cent suffered from chronic otitis media and 3.06 per cent suffered from otitis media with effusion. Acute otitis media was detected in 0.65 per cent and foreign bodies were found in 0.34 per cent of the children. CONCLUSION: Preventable ear diseases posed a significant health problem among children at primary school level. Regular screening of children during this stage would ensure that their school lives were not affected by hearing impairments or preventable ear disorders. Information gathered in this study will help in effective treatment prioritisation of ear disorders, planning and resource allocation.

Association of GPX1 polymorphism, GPX activity and prostate cancer risk.

Prostate cancer is the second most common cancer in men worldwide. Although the aetiology of this disease remains largely unclear, several lines of evidence suggest that oxidative stress plays a role in prostate carcinogenesis. The antioxidant enzyme glutathione peroxidase 1 (GPX1) is part of the enzymatic antioxidant defence, preventing oxidative damage to DNA, proteins and lipids by detoxifying hydrogen and lipid peroxides that may contribute to prostate cancer development. Some studies indicate an association between GPX1 Pro198Leu polymorphism and an increased risk of cancer. The purpose of the present study was to determine the possible association of GPX1 Pro198Leu polymorphism and erythrocyte GPX activity with the risk of developing prostate cancer and to clarify whether erythrocyte GPX activity levels were correlated with the GPX1 Pro198Leu genotype in the Turkish population. The GPX1 Pro198Leu genotype was determined in 33 prostate cancer patients and 91 control individuals. As evident from our results, there was no difference between genotype and/or allele frequencies in prostate cancer patients and controls. No significant difference was found in GPX1 genotype or allele frequency between aggressive and non-aggressive prostate cancer patients. It can be suggested with these findings that individual susceptibility of prostate cancer may be modulated by GPX1 polymorphism, but it needs further studies.

Prolonged foreign body impaction in the oesophagus.

It is not unusual for a foreign body to be swallowed and become lodged in the oesophagus. It is, however, very unusual for such a foreign body to remain lodged for a period of six months. This particular case, a 37-year-old man, is interesting because of the length of time the foreign body, a denture, remained in the oesophagus without complications, its successful removal and the nature of the foreign body, which is prone to cause complications on prolonged stay or during removal.