Mycobacterium oryzae sp. nov., a scotochromogenic, rapidly growing species is able to infect human macrophage cell line.

Gram-stain-positive, acid-fast-positive, rapidly growing, rod-shaped bacteria (designated as strains JC290T, JC430 and JC431) were isolated from paddy cultivated soils on the Western Ghats of India. Phylogenetic analysis placed the three strains among the rapidly growing mycobacteria, being most closely related to Mycobacterium tokaiense 47503T (98.8 % 16S rRNA gene sequence similarity), Mycobacterium murale MA112/96T (98.8 %) and a few other Mycobacterium species. The level of DNA-DNA reassociation of the three strains with M. tokaiense DSM 44635T was 23.4±4 % (26.1±3 %, reciprocal analysis) and 21.4±2 % (22.1±4 %, reciprocal analysis). The three novel strains shared >99.9 % 16S rRNA gene sequence similarity and DNA-DNA reassociation values >85 %. Furthermore, phylogenetic analysis based on concatenated sequences (3071 bp) of four housekeeping genes (16S rRNA, hsp65, rpoB and sodA) revealed that strain JC290T is clearly distinct from all other Mycobacteriumspecies. The three strains had diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositolmannosides, unidentified phospholipids, unidentified glycolipids and an unidentified lipid as polar lipids. The predominant isoprenoid quinone for all three strains was MK-9(H2). Fatty acids were C17 : 1ω7c, C16 : 0, C18 : 1ω9c, C16 : 1ω7c/C16 : 1ω6c and C19 : 1ω7c/C19 : 1ω6c for all the three strains. On the basis of phenotypic, chemotaxonomic and phylogenetic data, it was concluded that strains JC290T, JC430 and JC431 are members of a novel species within the genus Mycobacterium and for which the name Mycobacterium oryzae sp. nov. is proposed. The type strain is JC290T (=KCTC 39560T=LMG 28809T).

Is malnutrition a risk factor of stroke?

Obesity is an established risk factor of stroke. Malnutrition in post-stroke period is common and can influence outcome. But malnutrition, though predicted, has not yet been established as a risk factor of stroke. This descriptive study was carried out in the Department of Neurology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka and Department of Neurology, Dhaka Medical College (DMC), from January 2009 to December 2010 to explore whether malnutrition is an independent risk factor of stroke. Nutritional status of 100 stroke patients and 100 healthy controls were assessed in this study. Anthropometric measurements including Body Mass Index (BMI), Triceps skin fold (TSF), Mid-arm circumference (MAC) and Arm-muscle circumference (AMC) were measured within 7 days of stroke. Haemoglobin and haematocrit percentage, serum iron and serum albumin were measured at the same time. No significant difference was observed regarding TSF thickness, MAC, AMC, mean Hb and mean albumin level between the stroke patients and the control group, although iron level was significantly lower in stroke group. Multiple logistic regressions analysis showed that increase in age, smoking and decreased serum iron level has a positive association with stroke. Malnutrition is, according to this study, not a significant risk factor of stroke and triceps skin fold (TSF) thickness, mid-arm circumference (MAC), arm-muscle circumference (AMC), hemoglobin and serum albumin are not appropriate predictor of stroke.

Incidence of diabetes mellitus in a population-based cohort of HIV-infected and non-HIV-infected persons: the impact of clinical and therapeutic factors over time.

AIMS: To examine incidence density rate and correlates of incident diabetes mellitus in a cohort of HIV-infected individuals compared with matched non-HIV-infected persons. METHODS: Data were obtained from the South Carolina Medicaid system and the enhanced HIV/AIDS Reporting System surveillance database for persons ≥ 18 years of age who had been attended to during the period 1994 to 2011. Time-dependent proportional hazards analysis and marginal structural models were used to analyse the data. RESULTS: A total of 13 632 individuals (6816, 1:1 matched HIV-infected and non-HIV-infected persons; median age 39 years; 57% male) contributed 88 359 person-years of follow-up. Incidence rate of diabetes was higher in the non-HIV-infected group compared with the HIV-infected group (13.60 vs. 11.35 per 1000 person-years). Multivariable hazards analysis suggested a significantly lower risk of incident diabetes among HIV-infected persons treated with combination antiretroviral therapy compared with the matched non-HIV-infected persons (adjusted hazards ratio 0.55; 95% CI 0.46-0.65). Among HIV-infected persons, marginal structural modelling suggested a significantly higher risk of diabetes with cumulative exposure to protease inhibitors over the observation period (adjusted relative risk 1.35; 95% CI 1.03-1.78), but this association was not significant for exposure to non-nucleoside reverse transcriptase inhibitors. Overall, female gender, older age, non-white race/ethnicity, and pre-existing hypertension, dyslipidaemia, obesity and hepatitis C infection were associated with higher risk of diabetes incidence. CONCLUSIONS: HIV infection may not be independently associated with increased risk of diabetes. Among HIV-infected persons, exposure to protease inhibitor-based regimens may increase the risk of diabetes. Healthcare providers should make every effort to use combination antiretroviral therapy regimens with a better cardiometabolic profile.

A rabbit eye model for in vivo transformation of progenetic metacercariae of Clinostomum complanatum into ovigerous adult worms.

Clinostomum complanatum is a digenetic trematode that causes yellow grub disease in some fish species and also shows zoonotic potential by sporadically infecting humans. In this study, progenetic metacercariae of C. complanatum were obtained from the fish Trichogaster fasciatus, and were aseptically placed in conjunctival incisions made in the superior and inferior fornices of the eye of rabbits, which served as the experimental hosts. Worms were harvested without necropsy of the host on days 4 and 8 post infection, to observe in vivo transformation of the progenetic metacercariae into ovigerous adult worms. The worms appeared to cause minimal damage to the host although they were tenaciously attached. In vivo maturation was evident by the development of the vitellaria, enlargement of gonads, the presence of a large number of shelled eggs in a distended uterus and ramifications of the intestinal caeca. Obtaining mature ovigerous worms without sacrificing the host clearly gives the rabbit eye model an advantage over those described previously. Due to the relative advantage of the short time required for maturation and the prolific egg production by C. complanatum, it is suggested that this host-parasite system could be used as an excellent model for classroom teaching of trematode biology and to investigate the cues involved in in vivo transformation and host-parasite interactions.

Discovery of serum biomarkers for diagnosis of tuberculosis by NMR metabolomics including cross-validation with a second cohort.

BACKGROUND: Tuberculosis (TB) is a disease with worldwide presence and a major cause of death in several developing countries. Current diagnostic methodologies often lack specificity and sensitivity, whereas a long time is needed to obtain a conclusive result. METHODS: In an effort to develop better diagnostic methods, this study aimed at the discovery of a biomarker signature for TB diagnosis using a Nuclear Magnetic Resonance based metabolomics approach. In this study, we acquired 1H NMR spectra of blood serum samples of groups of healthy subjects, individuals with latent TB and of patients with pulmonary and extra-pulmonary TB. The resulting data were treated with uni- and multivariate statistical analysis. RESULTS: Six metabolites (inosine, hypoxanthine, mannose, asparagine, aspartate and glutamate) were validated by an independent cohort, all of them related with metabolic processes described as associated with TB infection. CONCLUSION: The findings of the study are according with the WHO Target Product Profile recommendations for a triage test to rule-out active TB.

Comparative study between combination of famciclovir and prednisolone with prednisolone alone in acute Bell's palsy.

The antiviral drug acyclovir or its analogue, valacyclovir, has been applied in various trials on Bell's palsy with inconsistent results. We compared the therapeutic effect of famciclovir plus prednisolone with prednisolone alone, in patients with Bell's palsy. In a randomized, prospective trial, 68 patients were randomized to treatment with famciclovir and prednisolone (34 patients) or prednisolone alone (34 patients). All patients underwent supportive therapy. Severity of Bell's palsy was evaluated using the House-Brackmann scale (HBS). Follow-up was done after 1 week, 1 month and 3 months, with complete recovery defined as House-Brackmann grade I. The analysis revealed that recovery rates at month 1 and 3 were significantly higher in combination group than that of prednisolone only group (94.1% vs. 61.8% and 97.1% vs. 74.5% respectively). Again recovery from mild to moderate (HBS-II, III, IV) Bell's palsy occurred completely at month 3 and that of severe (HBS-V, VI) Bell's palsy was two-third of the patients. Again in severe Bell's palsy combination treatment increased the chance of complete recovery more than 10-fold than that of steroid only. The study results suggest that better outcome for Bell's palsy patients occurred if they were treated with prednisolone and famciclovir combination instead of prednisolone alone. In fact a considerable number of patients were benefited from additional antiviral therapy with famciclovir.

The family planning "know-do" gap among married women of reproductive age in urban Pakistan.

OBJECTIVE: To examine the prevalence and predictors of family planning (FP) know-do gaps among married women of reproductive age (MWRA) in low socio-economic urban areas of Karachi, Pakistan. DESIGN: This was a cross-sectional survey of randomly selected 7288 MWRA (16-49 years) to identify predictors of the know-do gap in FP using a logistic regression model. RESULTS: More than one third (35.5%) of MWRA had FP know-do gap, i.e., despite having a knowledge of contraceptives and desire to limit or delay childbearing, they were not using contraceptives. Women were less likely to use FP if they were getting older (25-35 years: OR 1.45, 95% CI 1.09-1.94; >35 years: OR 3.02, 95% CI 1.90-4.80), from certain ethnicities (Sindhi: OR 1.64, 95% CI 1.11-2.42; Saraiki: OR 1.66, 95% CI 1.01-2.71; other minorities: OR 2.37, 95% CI 1.63-3.44); did not receive FP counselling: OR 1.43, 95% CI 1.13-1.80; and had not made a joint decision on FP: OR 1.44, 95% CI 1.06-1.98). Conversely, women were more likely to use contraceptives if they had >10 years of schooling (OR 0.66, 95% CI 0.46-0.94), with each increasing number of a living child (OR 0.68, 95% CI 0.62-0.75) and each increasing number of contraceptive method known (OR 0.93, 95% CI 0.88-0.98). CONCLUSION: The predictors associated with the FP know-do gap among MWRA should be considered when planning future strategies to improve the contraceptive prevalence rate in Pakistan.

OBJECTIF: Étudier la prévalence et les variables explicatives du fossé entre informations et actions en matière de planification familiale (FP) chez les femmes mariées en âge de procréer (MWRA) dans les quartiers urbains socio-économiquement défavorisés de Karachi, Pakistan. PLAN: Enquête transversale réalisée auprès de 7 288 MWRA (16­49 ans) sélectionnées de manière aléatoire visant à identifier les variables explicatives du fossé entre informations et actions en matière de FP en utilisant un modèle de régression logistique. RÉSULTATS: Un fossé entre informations et actions en matière de FP a été observé chez plus d'un tiers (35,5%) des MWRA, c.-à-d., qu'en dépit de connaissances sur les moyens de contraception et d'un souhait de limiter ou retarder les grossesses, ces femmes n'utilisaient aucun moyen de contraception. Les femmes étaient moins susceptibles d'avoir recours à la FP en vieillissant (25­35 ans : OR 1,45 ; IC 95% 1,09­1,94 ; >35 ans : OR 3,02 ; IC 95% 1,90­4,80), si elles appartenaient à certains groupes ethniques (Sindhi : OR 1,64 ; IC 95% 1,11­2,42 ; Saraiki : OR 1,66 ; IC 95% 1,01­2,71 ; autres minorités : OR 2,37 ; IC 95% 1,63­3,44), si elles ne bénéficiaient d'aucune aide en matière de FP (OR 1,43 ; IC 95% 1,13­1,80), et si la décision relative à la FP avait été prise unilatéralement (OR 1,44 ; IC 95% 1,06­1,98). À l'inverse, les femmes étaient plus susceptibles d'utiliser des contraceptifs si elles avaient été scolarisées pendant >10 ans (OR 0,66, ; IC 95% 0,46­0,94), à mesure que leur nombre d'enfants vivants augmentait (OR 0,68 ; IC 95% 0,62­0,75) et à mesure que le nombre de moyens contraceptifs qui leur étaient connus augmentait (OR 0,93 ; IC 95% 0,88­0,98). CONCLUSION: Les variables explicatives associées au fossé entre informations et actions en matière de FP chez les MWRA devraient être prises en compte lors de la planification de futures stratégies visant à améliorer le taux de prévalence des contraceptifs au Pakistan.

Disparities in the Use of Mechanical Thrombectomy Alone Compared with Adjunctive Intravenous Thrombolysis in Acute Ischemic Stroke in the United States.

BACKGROUND AND PURPOSE: For patients with large-vessel occlusion, mechanical thrombectomy (MT) without IV-tPA is a proved strategy. The relative benefit of direct MT versus MT+IV-tPA for patients with indications for IV-tPA is being actively investigated. We used a national inpatient database to assess trends in use and patient profiles after MT+IV-tPA versus mechanical thrombectomy alone. MATERIALS AND METHODS: The National Inpatient Sample was queried between 2013 and 2018 for patients undergoing mechanical thrombectomy for acute ischemic stroke. Patients who received mechanical thrombectomy alone were compared with those who underwent MT+IV-tPA. The Cochran-Armitage test was conducted to assess the linear trend of use of mechanical thrombectomy alone among the entire cohort and between admissions involving non-White and White patients. All estimates were nationalized using discharge weights. RESULTS: A total of 89,645 weighted admissions were identified pertaining to mechanical thrombectomy for acute ischemic stroke from 2013 to 2018. Of these, 59,935 (66.9%) admissions involved mechanical thrombectomy alone. There was an increase in the trend toward the use of mechanical thrombectomy alone (trend: 3.26%; P < .001) per year. Multivariable regression analysis regarding patient profiles indicated that patients who identified as Black (OR = 0.83, P = .001) or Hispanic (OR = 0.79; P < .001) were more likely to undergo mechanical thrombectomy alone compared with those who identified as White. There was no statistically significant difference in the slope between non-White and White populations receiving mechanical thrombectomy alone (trend: +0.93% in favor of non-White; P = .096). CONCLUSIONS: Our results indicated that mechanical thrombectomy alone was used more frequently than MT+IV-tPA among patients with acute ischemic stroke. The disparity between those who identify as White and non-White persisted across the years, though it is closing.

Serum triglyceride level in type 2 diabetes mellitus patients with or without frozen shoulder.

BACKGROUND: Musculoskeletal disorders are very common among the diabetic patients and frozen shoulder is one of the disabling conditions. The present study was conducted to compare the serum triglyceride level among the patients of type 2 diabetic presented with and without frozen shoulder. METHODOLOGY: This case control study was conducted from January 2008 to December 2009, in the department of Physical Medicine and Rehabilitation, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka with an aim to compare the serum triglyceride level among diabetic patients presented with, and without frozen shoulder. Thirty types 2 diabetic patients with frozen shoulder were selected as cases and similar number well matched type 2 diabetic patients without frozen shoulder were selected as control. RESULTS: We prospectively studied 30 diabetes mellitus (type 2) patients with the diagnosis of frozen shoulder. The blood sugar both fasting and 2 hours after breakfast, HbA1c and serum triglyceride levels were measured in all patients and compared with those in 30 diabetic patients without frozen shoulder. The blood sugar, fasting and 2 hours after breakfast, HbA1C and serum triglyceride levels were significantly elevated in the frozen-shoulder group (fasting blood sugar p = 0.012; blood sugar 2 hours after breakfast p < 0.01; HbA1c p < 0.05; and triglyceride p < 0.001). CONCLUSION: Diabetic type 2 patients presented with frozen shoulder had higher serum triglyceride level compare to the diabetic type 2 patients without frozen shoulder.

Long-Term Rupture Risk in Patients with Unruptured Intracranial Aneurysms Treated with Endovascular Therapy: A Systematic Review and Meta-Analysis.

BACKGROUND: Surveillance imaging of previously unruptured, coiled aneurysms remains routine even though reports of rupture of these aneurysms are extremely rare. PURPOSE: We performed meta-analysis to examine long-term rupture risk over ≥1-year follow-up duration in patients with unruptured intracranial aneurysm who underwent endovascular therapy. DATA SOURCES: Multiple databases were searched for relevant publications between 1995 and 2018. STUDY SELECTION: Studies reporting outcome of long-term rupture risk over ≥1-year follow-up in treated patients with unruptured intracranial aneurysms were included. DATA ANALYSIS: Random effects meta-analysis was used, and results were expressed as long-term rupture rate per 100 patient-year with respective 95% CIs. For ruptured aneurysms during follow-up, data were collected on size and completeness of initial Treatment. DATA SYNTHESIS: Twenty-four studies were identified. Among 4842 patients with a mean follow-up duration of 3.2 years, a total of 12 patients (0.25%) experienced rupture of previous unruptured intracranial aneurysms after endovascular treatment. Nine of these 12 patients harbored aneurysms that were large, incompletely treated, or both. A total of 2 anterior circulation, small, completely coiled aneurysms subsequently ruptured. The long-term rupture rate per 100 patient-year for unruptured intracranial aneurysms treated with endovascular therapy was 0.48 (95% CI, 0.45-0.51). Retreatment was carried out in 236 (4.9%) of these 4842 patients. LIMITATIONS: A limitation of the study is that a lack of systematic nature of follow-up and mean follow-up duration of 3.2 years are not sufficient to make general recommendations about aneurysm followup paradigms. CONCLUSIONS: Given a 5% retreatment rate, postcoil embolization spontaneous rupture of previously unruptured, small- and medium-sized, well-treated aneurysms is exceedingly rare.

Active and prospective latent tuberculosis are associated with different metabolomic profiles: clinical potential for the identification of rapid and non-invasive biomarkers.

Although 23% of world population is infected with Mycobacterium tuberculosis (M. tb), only 5-10% manifest the disease. Individuals surely exposed to M. tb that remain asymptomatic are considered potential latent TB (LTB) cases. Such asymptomatic M. tb.-exposed individuals represent a reservoir for active TB cases. Although accurate discrimination and early treatment of patients with active TB and asymptomatic M. tb.-exposed individuals are necessary to control TB, identifying those individuals at risk of developing active TB still remains a tremendous clinical challenge. This study aimed to characterize the differences in the serum metabolic profile specifically associated to active TB infected individuals or to asymptomatic M. tb.-exposed population. Interestingly, significant changes in a specific set of metabolites were shared when comparing either asymptomatic house-hold contacts of active TB patients (HHC-TB) or active TB patients (A-TB) to clinically healthy controls (HC). Furthermore, this analysis revealed statistically significant lower serum levels of aminoacids such as alanine, lysine, glutamate and glutamine, and citrate and choline in patients with A-TB, when compared to HHC-TB. The predictive ability of these metabolic changes was also evaluated. Although further validation in independent cohorts and comparison with other pulmonary infectious diseases will be necessary to assess the clinical potential, this analysis enabled the discrimination between HHC-TB and A-TB patients with an AUC value of 0.904 (confidence interval 0.81-1.00, p-value < 0.0001). Overall, the strategy described in this work could provide a sensitive, specific, and minimally invasive method that could eventually be translated into a clinical tool for TB control.

Search for new pharmacophores for antimalarial activity. Part I: synthesis and antimalarial activity of new 2-methyl-6-ureido-4-quinolinamides.

A total of 80 new 2-methyl-6-ureido-4-quinolinamides were synthesized and evaluated for their antimalarial activity. Several analogs elicited the antimalarial effect at MIC of 0.25 mg/mL against the chlooquine-sensitive P. falciparum strain. The IC(50) values of the active compounds were observed to be in ng/mL range and two of the analogs have better IC(50) value than the standard chloroquine. In the in vivo assay against mdr CQ resistant P. yoelii N67/P. yoelii nigeriensis, however, none of the compound showed complete suppression of parasitemia on day 7. One of the compounds displayed significant antibacterial effect against several strains of bacteria and was many-fold better than the standard drug gentamicin.

Detecting relapse in youth with psychotic disorders utilizing patient-generated and patient-contributed digital data from Facebook.

Although most patients who experience a first-episode of psychosis achieve remission of positive psychotic symptoms, relapse is common. Existing relapse evaluation strategies are limited by their reliance on direct and timely contact with professionals, and accurate reporting of symptoms. A method by which to objectively identify early relapse warning signs could facilitate swift intervention. We collected 52,815 Facebook posts across 51 participants with recent onset psychosis (mean age = 23.96 years; 70.58% male) and applied anomaly detection to explore linguistic and behavioral changes associated with psychotic relapse. We built a one-class classification model that makes patient-specific personalized predictions on risk to relapse. Significant differences were identified in the words posted to Facebook in the month preceding a relapse hospitalization compared to periods of relative health, including increased usage of words belonging to the swear (p < 0.0001, Wilcoxon signed rank test), anger (p < 0.001), and death (p < 0.0001) categories, decreased usage of words belonging to work (p = 0.00579), friends (p < 0.0001), and health (p < 0.0001) categories, as well as a significantly increased use of first (p < 0.0001) and second-person (p < 0.001) pronouns. We additionally observed a significant increase in co-tagging (p < 0.001) and friending (p < 0.0001) behaviors in the month before a relapse hospitalization. Our classifier achieved a specificity of 0.71 in predicting relapse. Results indicate that social media activity captures objective linguistic and behavioral markers of psychotic relapse in young individuals with recent onset psychosis. Machine-learning models were capable of making personalized predictions of imminent relapse hospitalizations at the patient-specific level.

Exercise capacity reflects airflow limitation rather than hypoxaemia in patients with pulmonary arteriovenous malformations.

BACKGROUND: Pulmonary arteriovenous malformations (PAVMs) generate a right-to-left shunt. Impaired gas exchange results in hypoxaemia and impaired CO2 clearance. Most patients compensate effectively but some are dyspneic, and these are rarely the most hypoxaemic. AIM: To test degrees of concurrent pathology influencing exercise capacity. DESIGN: Replicate, sequential single centre, prospective studies. METHODS: Cardiopulmonary exercise tests (CPETs) were performed in 26 patients with PAVMs, including individuals with and without known airflow obstruction. To replicate, relationships were tested prospectively in an independent cohort where self-reported exercise capacity evaluated by the Veterans Specific Activity Questionnaire (VSAQ) was used to calculate metabolic equivalents (METs) at peak exercise (n = 71). Additional measurements included oxygen saturation (SpO2), forced expiratory volume in 1 s (FEV1), vital capacity (VC), fractional exhaled nitric oxide (FeNO), haemoglobin and iron indices. RESULTS: By CPET, the peak work rate was only minimally associated with low SpO2 or low arterial oxygen content (calculated as CaO2=1.34 × SpO2 × haemoglobin), but was reduced in patients with low FEV1 or VC. Supranormal work rates were seen in patients with severe right-to-left shunting and SpO2 < 90%, but only if FEV1 was >80% predicted. VSAQ-calculated METS also demonstrated little relationship with SpO2, and in crude and CaO2-adjusted regression, were lower in patients with lower FEV1 or VC. Bronchodilation increased airflow even where spirometry was in the normal range: exhaled nitric oxide measurements were normal in 80% of cases, and unrelated to any PAVM-specific variable. CONCLUSIONS: Exercise capacity is reduced by relatively mild airflow limitation (obstructive or restrictive) in the setting of PAVMs.

Antibiotic prescribing practices in primary and secondary health care facilities in Uttar Pradesh, India.

BACKGROUND: Emerging antibiotic resistance in common pathogens is a worldwide problem known to be related to inappropriate overuse of antibiotics. Wide variability in antibiotic use throughout the world is because of various factors, including socio-cultural differences. OBJECTIVE: To study the rate of antibiotic prescribing for common outpatient illnesses and the various disease, patient, physician and health facility characteristics, which influence this in primary and secondary healthcare settings in Uttar Pradesh. METHODS: After sampling of health facilities - both private and government, rural and urban, a cross-sectional survey of prescriptions for patients presenting with runny or blocked nose, cough, sore throat, diarrhoea or fever without localizing symptoms was conducted. Information on disease, patient, physician and facility characteristics was collected. Outcome factors: antibiotic prescription and group of antibiotic prescribed. No intervention was made. RESULTS: Overall antibiotic prescription rate was 81.8%. It was significantly higher in urban private than in government settings, and higher in rural than in urban settings. Presence of fever prompted antibiotic use across all strata. Lower age of patients and higher socioeconomic status were associated with higher antibiotic use. Patient requests for antibiotics were very rare. Specialist practices with staff with higher qualifications and better opportunities for updating knowledge were associated with lower antibiotic prescribing. Government health-facilities with larger staff complement and better infrastructure was associated with lower prescribing rates. The most common antimicrobial agents used were the penicillin, sulfonamides and fluoroquinolones. Injection use paralleled antibiotic use. CONCLUSIONS: These data on overprescribing of antibiotics can be used to design educational programs for physicians working in these settings.

Direct evidence that protein kinase C plays an essential role in the development of late preconditioning against myocardial stunning in conscious rabbits and that epsilon is the isoform involved.

Brief ischemic episodes confer marked protection against myocardial stunning 1-3 d later (late preconditioning [PC] against stunning). The mechanism of this powerful protective effect is poorly understood. Although protein kinase C (PKC) has been implicated in PC against infarction, it is unknown whether it triggers late PC against stunning. In addition, the entire PKC hypothesis of ischemic PC remains controversial, possibly because the effects of PKC inhibitors on PC protection have not been correlated with their effects on PKC activity and/or translocation in vivo. Thus, conscious rabbits underwent a sequence of six 4-min coronary occlusion (O)/4-min reperfusion (R) cycles for three consecutive days (days 1, 2, and 3). In the control group (group I, n = 7), the recovery of systolic wall thickening after the six O/R cycles was markedly improved on days 2 and 3 compared with day 1, indicating the development of late PC against stunning. Administration of the PKC inhibitor chelerythrine at a dose of 5 mg/kg before the first O on day 1 (group II, n = 10) abrogated the late PC effect against stunning, whereas a 10-fold lower dose (0.5 mg/kg; group III, n = 7) did not. Administration of 5 mg/kg of chelerythrine 10 min after the sixth reperfusion on day 1 (group IV, n = 6) failed to block late PC against stunning. When rabbits were given 5 mg/kg of chelerythrine in the absence of O/R (group V, n = 5), the severity of myocardial stunning 24 h later was not modified. Pretreatment with phorbol 12-myristate 13-acetate (4 microg/kg) on day 1 without ischemia (group VI, n = 11) induced late PC against stunning on day 2 and the magnitude of this effect was equivalent to that observed after ischemic PC. In vehicle-treated rabbits (group VIII, n = 5), the six O/R cycles caused translocation of PKC isoforms epsilon and eta from the cytosolic to the particulate fraction without significant changes in total PKC activity, in the subcellular distribution of total PKC activity, or in the subcellular distribution of the alpha, beta1, beta2, gamma, delta, zeta, iota, lambda, and mu isoforms. The higher dose of chelerythrine (5 mg/kg; group X, n = 5) prevented the translocation of both PKC epsilon and eta induced by ischemic PC, whereas the lower dose (0.5 mg/kg; group XI, n = 5) prevented the translocation of PKC eta but not that of epsilon, indicating that the activation of epsilon is necessary for late PC to occur whereas that of eta is not. To our knowledge, this is the first demonstration that a PKC inhibitor actually prevents the translocation of PKC induced by ischemic PC in vivo, and that this inhibition of PKC translocation results in loss of PC protection. Taken together, the results demonstrate that the mechanism of late PC against myocardial stunning in conscious rabbits involves a PKC-mediated signaling pathway, and implicate epsilon as the specific PKC isoform responsible for the development of this cardioprotective phenomenon.

Efficacy of isoniazid prophylaxis in renal allograft recipients.

The efficacy of isoniazid (INH) prophylaxis in renal allograft recipients who are on long-term immunosuppression in a region highly prevalent for tuberculosis (TB) was studied. INH (300 mg/d in patients weighing more than 35 kg and 5 mg/kg/d in patients with <35 kg body weight) together with Pyridoxine 50 mg/d for 1 year was started in randomly assigned renal allograft recipients. Occurrence of clinical tuberculosis during the initial 2 years posttransplantation was observed in the risk group and patients at no risk. Risks were defined as acute rejection episodes and exposure to antirejection therapy, past history of TB completely or incompletely treated, radiological evidence of past tuberculosis, history of tuberculosis in close contacts. Among 480 patients registered in the study, INH prophylaxis was given to 219 randomly assigned renal allograft recipients. Results were compared among patients developing TB during the initial 2 years posttransplantation in both the groups. Risk factors were analyzed for comparison in both groups. No significant difference was observed in terms of past history of TB, TB in close contacts, episodes of acute rejection during the initial 3 months, and comorbidities such as cytomegalovirus infection, hepatitis C virus infection, and posttransplant diabetes. One patient from the INH group and 10 patients from the non-INH group developed TB during the initial 2 years posttransplantation (P < .0001). None of patients required discontinuation of INH. INH was observed to be safe and effective as a chemoprophylactic agent in renal allograft recipients.

Outcome of pregnancy in renal allograft recipients: SIUT experience.

The course of pregnancy and its outcome was studied in renal allograft recipients. Between November 1985 and November 2005, a total of 1481 renal transplants were carried out at the Sindh Institute of Urology and Transplantation (SIUT); among them were 348 females, with 73 potential females for pregnancy. All patients received cyclosporine and prednisolone, with 82% also receiving azathioprine and 4 patients mycophenolate mofetil as a third immunosuppressant drug. We evaluated incidence of hypertension, diabetes, pre-eclampsia, urinary tract infection (UTI), rejection during pregnancy and during 3 months' postdelivery as well as outcomes of pregnancy. Among 73 potential candidates, 31 had 47 pregnancies, after an average of 31 months (8-86 months). Of 31 subjects, 21 subjects were hypertensive on one or two drugs prior to conception. A rise in blood pressure during pregnancy was noticed in 7 patients. Albuminuria from trace to 3+ appeared in 13 patients and glycosuria in one other. Blood sugar levels remained within normal range in all subjects. UTIs occurred during pregnancy in 7 patients. Among 47 pregnancies, 9 had abortions (7 spontaneous, 2 therapeutic) and 6 had preterm deliveries. The others were full-term deliveries: 12 via a lower segment caesarean section and 20 were normal vaginal deliveries. Average birth weight was 4.8 lbs. At an average follow-up of 38 months the serum creatinine values ranged from 0.94 to 2.3 mg %. One patient developed acute irreversible graft dysfunction soon after delivery. Our study demonstrated that pregnancy did not reduce renal graft survival, but newborns are at greater risk of premature birth and low birth weight.

Use of Xpert(®) MTB/RIF assay in the first national anti-tuberculosis drug resistance survey in Pakistan.

SETTING: The first national anti-tuberculosis drug resistance survey in Pakistan, a high tuberculosis (TB) and low human immunodeficiency virus (HIV) burden country. OBJECTIVE: To determine the proportion of patients with multidrug-resistant TB (MDR-TB) and to compare the performance of Xpert(®) MTB/RIF with conventional phenotypic drug susceptibility testing (DST). METHODS: Sputum samples were collected from 1972 consecutively enrolled pulmonary TB patients from 40 clusters. Phenotypic DST was performed in parallel with Xpert. RESULTS: The proportion of MDR-TB patients was 3.7% (95%CI 2.5-5.0) among new and 18.1% (95%CI 13.0-23.4) among previously treated cases. A valid rifampicin (RMP) testing result was available from substantially more cases with Xpert (n = 1809) than with phenotypic DST (n = 1592). Among strains with discordant results, rpoB sequencing revealed only one false-resistant result (new TB case) with Xpert and 7.7% (8/104) of RMP-resistant cases missed with Xpert against 3.8% (4/14) by phenotypic DST. This difference was not significant. CONCLUSIONS: This survey provides the first representative data for Pakistan on its MDR-TB burden. The Xpert assay had nearly 100% specificity, even in a low MDR-TB prevalence setting. The use of this assay greatly simplifies survey logistics, making it a feasible option for survey implementation, especially in resource-constrained settings.