Drug-resistant tuberculosis in six hospitals in Rio de Janeiro, Brazil

SETTING: Tuberculosis (TB) drug resistance survey in six hospitals in Rio de Janeiro, Brazil. OBJECTIVE: To estimate resistance to at least one drug (DR) and multidrug resistance (MDR) and identify associated factors. DESIGN: One-year cross-sectional survey. Hospitals were included as a convenience sample. RESULTS: Of 595 patients investigated, 156 (26.2%) had previously undergone anti-tuberculosis treatment, 433 (72.8%) were not previously treated and information on the remaining 6 was not available. Overall, DR and MDR rates were high, at respectively 102 (17.1%, 95%CI 14.3-20.5) and 44 (7.4%, 95%CI 5.5-9.9) cases. Among individuals not previously treated, 17 had MDR (3.9%, 95%CI 2.4-6.3) and diagnosis in a TB reference hospital was independently associated with MDR (prevalence ratio [PR] 3.3, 95%CI 1.2-8.7) after multivariate analysis. Among previously treated individuals, 27 had MDR (17.3%, 95%CI 11.7-24.2). MDR-TB was independently associated with diagnosis in a TB reference hospital (PR 3.6, 95%CI 1.5-8.7), male sex (PR 2.3,95%CI 1.2-4.4) and dyspnoea (PR 0.3, 95%CI 0.1-0.7). CONCLUSION: We found high levels of DR- and MDR-TB. Our study design did not permit us to determine the contribution of community versus nosocomial transmission. Further studies are needed to establish this. Nevertheless, hospitals should be recognised as a potential source of transmission of resistant TB strains and urgent measures to avoid nosocomial TB transmission should be taken.

Stigmatization of alcohol and other drug users by primary care providers in Southeast Brazil

This study reports on the views of Primary Health Care (PHC) providers in Southeast Brazil on the use of alcohol and other drugs which reflect stigma, moralization, or negative judgment. Six hundred nine PHC professionals from the Brazilian states of Sao Paulo and Minas Gerais took part in the study. The majority (86.5%) of these professionals were female. Attitudes toward the use of alcohol and other drugs were evaluated in comparison to Hansen`s disease, obesity, depression, schizophrenia. HIV/AIDS, and tobacco use. The use of tobacco, marijuana/cocaine, and alcohol were the most negatively judged behaviors (p < 0.05). Nursing assistants and community health care workers demonstrated the severest judgment of alcohol use. In addition, marijuana/cocaine addicts and alcoholics suffered the highest rate of rejection by professionals. The hypothesis that the use of alcohol and other drugs is a behavior stigmatized by health professionals being confirmed, it is important to develop strategies for changing provider attitudes in order to provide a higher quality of service to these patients. This study is important as a first study among PHC professionals about social stigma of alcohol and other drugs users. (C) 2009 Elsevier Ltd. All rights reserved.

Modulation of Mediotemporal and Ventrostriatal Function in Humans by Delta 9-Tetrahydrocannabinol A Neural Basis for the Effects of Cannabis sativa on Learning and Psychosis

Context: Cannabis sativa use can impair verbal learning, provoke acute psychosis, and increase the risk of schizophrenia. It is unclear where C sativa acts in the human brain to modulate verbal learning and to induce psychotic symptoms. Objectives: To investigate the effects of 2 main psychoactive constituents of C sativa, Delta 9-tetrahydrocannabinol (Delta 9-THC) and cannabidiol, on regional brain function during verbal paired associate learning. Design: Subjects were studied on 3 separate occasions using a block design functional magnetic resonance imaging paradigm while performing a verbal paired associate learning task. Each imaging session was preceded by the ingestion of Delta 9-THC (10 mg), cannabidiol (600 mg), or placebo in a double-blind, randomized, placebo-controlled, repeated-measures, within-subject design. Setting: University research center. Participants: Fifteen healthy, native English-speaking, right-handed men of white race/ethnicity who had used C sativa 15 times or less and had minimal exposure to other illicit drugs in their lifetime. Main Outcome Measures: Regional brain activation ( blood oxygen level-dependent response), performance in a verbal learning task, and objective and subjective ratings of psychotic symptoms, anxiety, intoxication, and sedation. Results: Delta 9-Tetrahydrocannabinol increased psychotic symptoms and levels of anxiety, intoxication, and sedation, whereas no significant effect was noted on these parameters following administration of cannabidiol. Performance in the verbal learning task was not significantly modulated by either drug. Administration of Delta 9-THC augmented activation in the parahippocampal gyrus during blocks 2 and 3 such that the normal linear decrement in activation across repeated encoding blocks was no longer evident. Delta 9-Tetrahydrocannabinol also attenuated the normal time-dependent change in ventrostriatal activation during retrieval of word pairs, which was directly correlated with concurrently induced psychotic symptoms. In contrast, administration of cannabidiol had no such effect. Conclusion: The modulation of mediotemporal and ventrostriatal function by Delta 9-THC may underlie the effects of C sativa on verbal learning and psychotic symptoms, respectively.

Evaluating budesonide efficacy in nasal polyposis and predicting the resistance to treatment

Cell resistance to glucocorticoids is a major problem in the treatment of nasal polyposis (NP). The objectives of this study were to observe the effect of budesonide on the expression of IL-1 beta, TNF-alpha, granulocyte macrophage-colony stimulating factor, intercellular adhesion molecule (ICAM)-1, basic fibroblast growth factor, eotaxin-2, glucocorticoid receptor (GR)-alpha, GR-beta, c-Fos and p65 in nasal polyps and to correlate their expression to clinical response. Biopsies from nasal polyps were obtained from 20 patients before and after treatment with topical budesonide. Clinical response to treatment was monitored by a questionnaire and nasal endoscopy. The mRNA levels of the studied genes were measured by real-time quantitative (RQ)-PCR. There was a significant decrease in the expression of TNF-alpha (P < 0.05), eotaxin-2 (P < 0.05) and p65 (P < 0.05) in NP after treatment. Poor responders to glucocorticoids showed higher expression of IL-1 beta (3.74 vs. 0.14; P < 0.005), ICAM-1 (1.91 vs. 0.29; P < 0.05) and p65 (0.70 vs. 0.16; P < 0.05) before treatment. Following treatment, IL-1 beta (4.18 vs. 0.42; P < 0.005) and GR-beta (0.95 vs. 0.28; P < 0.05) mRNA expression was higher in this group. Topical budesonide reduced the expression of TNF-alpha, eotaxin-2 and p65. Poor responders to topical budesonide exhibit higher levels of IL-1 beta, ICAM-1 and nuclear factor (NF)-kappa B at diagnosis and higher expression of both IL-1 beta and GR-beta after treatment. These results emphasize the anti-inflammatory action of topical budesonide at the molecular level and its importance in the treatment of NP. Nevertheless, IL-1 beta, ICAM-1 and NF-kappa B may be associated with primary resistance to glucocorticoids in NP, whereas higher expression of GR-beta in poor responders only after glucocorticoid treatment may represent a secondary drug resistance mechanism in this disease.

Comparison of clinical features and drug therapies among European and Latin American patients with juvenile dermatomyositis

Objective To compare the demographic features, presenting manifestations, diagnostic investigations, disease course, and drug therapies of children with juvenile dermatomyositis (JDM) followed in Europe and Latin America. Methods Patients were inception cohorts seen between 1980 and 2004 in 27 paediatric rheumatology centres. The following information was collected through the review of patient charts: sex; age at disease onset; date of disease onset and diagnosis; onset type; presenting clinical features; diagnostic investigations; course type; and medications received during disease course. Results Four hundred and ninety patients (65.5% females, mean onset age 7.0 years, mean disease duration 7.7 years) were included. Disease presentation was acute or insidious in 57.1% and 42.9% of the patients, respectively. The course type was monophasic in 41.3% of patients and chronic polycyclic or continuous in 58.6% of patients. The more common presenting manifestations were muscle weakness (84.9%), Gottron`s papules (72.9%), heliotrope rash (62%), and malar rash (56.7%). Overall, the demographic and clinical features of the 2 continental cohorts were comparable. European patients received more frequently high-dose intravenous methylprednisolone, cyclosporine, cyclophosphamide, and azathioprine, while methotrexate and antimalarials medications were used more commonly by Latin American physicians. Conclusion The demographic and clinical characteristics of JDM are similar in European and Latin American patients. We found, however, several differences in the use of medications between European and Latin American paediatric rheumatologists.

Is Suppression of Hypothalamic-Pituitary-Adrenal Axis Significant During Clinical Treatment of Phimosis?

Purpose: Corticoids have been an option for phimosis treatment since 1993. However, long-term use or repeated cycles pose a concern regarding drug absorption and consequent systemic effects. The aim of this study was to investigate the effect of topical corticoids used in treating phimosis on the hypothalamus-pituitary-adrenal axis in children. Materials and Methods: A total of 31 children were included in the study. Cortisol secretion was evaluated by the measurement of salivary cortisol in saliva samples collected at 9:00 a.m, before starting treatment and after 8 weeks of topical treatment with 0.05% clobetasol propionate. Salivary cortisol was determined by radioimmunoassay. To confirm that use of clobetasol propionate was not detected by the assay, the presence of cortisol circadian rhythm was checked by an extra saliva sample obtained at 11:00 p.m. from 10 children, and was observed to be maintained in all of them. Results: No significant difference in salivary cortisol levels was observed between samples obtained at 9:00 a.m. before starting treatment and after completing treatment when the entire group was analyzed. However, in 2 children the salivary cortisol levels after treatment were lower than the cutoff value (358 ng/dl) assumed to be suggestive of hypothalamus-pituitary-adrenal axis suppression. Conclusions: Topical clobetasol propionate used twice daily for clinical treatment of phimosis does not affect the hypothalamus-pituitary-adrenal axis in most patients. However, salivary cortisol level should be considered as a laboratory marker in long-term treatment or during repeated cycles to detect possible hypothalamus-pituitary-adrenal axis suppression.

Predictors of word-level literacy amongst Grade 3 children in five diverse languages

Groups of Grade 3 children were tested on measures of word-level literacy and undertook tasks that required the ability to associate sounds with letter sequences and that involved visual, auditory and phonological-processing skills. These groups came from different language backgrounds in which the language of instruction was Arabic, Chinese, English, Hungarian or Portuguese. Similar measures were used across the groups, with tests being adapted to be appropriate for the language of the children. Findings indicated that measures of decoding and phonological-processing skills were good predictors of word reading and spelling among Arabic- and English-speaking children, but were less able to predict variability in these same early literacy skills among Chinese- and Hungarian-speaking children, and were better at predicting variability in Portuguese word reading than spelling. Results were discussed with reference to the relative transparency of the script and issues of dyslexia assessment across languages. Overall, the findings argue for the need to take account of features of the orthography used to represent a language when developing assessment procedures for a particular language and that assessment of word-level literacy skills and a phonological perspective of dyslexia may not be universally applicable across all language contexts. Copyright (C) 2008 John Wiley & Sons, Ltd.

Determination of P-glycoprotein, MDR-related protein 1, breast cancer resistance protein, and lung-resistance protein expression in leukemic stem cells of acute myeloid leukemia

Background: The most primitive leukemic precursor in acute myeloid leukemia (AML) is thought to be the leukemic stem cell (LSC), which retains the properties of self-renewal and high proliferative capacity and quiescence of the hematopoietic stem cell. LSC seems to be immunophenotypically distinct and more resistant to chemotherapy than the more committed blasts. Considering that the multidrug resistance (MDR) constitutive expression may be a barrier to therapy in AML, we have investigated whether various MDR transporters were differentially expressed at the protein level by different leukemic subsets. Methods: The relative expression of the drug-efflux pumps P-gp, MRP, LRP, and BCRP was evaluated by mean fluorescence index (MFI) and the Kolmogorov-Smirnov analysis (D values) in five leukemic subpopulations: CD34(+)CD38(-)CD123(+) (LSCs), CD34(+)CD38(+)CD123(-), CD34(+)CD38(+)CD123(+), CD34(+)CD38(+)CD123(-), and CD34(-) mature cells in 26 bone marrow samples of CD34(+) AML cases. Results: The comparison between the two more immature subsets (LSC versus CD34(+)CD38(-)CD123(-) cells) revealed a higher P-gp, MRP, and LRP expression in LSCs. The comparative analysis between LSCs and subsets of intermediate maturation (CD34(+)CD38(+)) demonstrated the higher BCRP expression in the LSCs. In addition, P-gp expression was also significantly higher in the LSC compared to CD34(+)CD38(+)CD123(-) subpopulation. Finally, the comparative analysis between LSC and the most mature subset (CD34(-)) revealed higher MRP and LRP and lower P-gp expression in the LSCs. Conclusions: Considering the cellular heterogeneity of AML, the higher MDR transporters expression at the most immature, self-renewable, and quiescent LSC population reinforces that MDR is one of the mechanisms responsible for treatment failure. (C) 2008 Clinical Cytometry Society.

Cytokine Signatures of Innate and Adaptive Immunity in 17DD Yellow Fever Vaccinated Children and Its Association With the Level of Neutralizing Antibody

Background. The live attenuated yellow fever (YF) vaccines have been available for decades and are considered highly effective and one of the safest vaccines worldwide. Methods. The impact of YF-17DD-antigens recall on cytokine profiles of YF-17DD-vaccinated children were characterized using short-term cultures of whole blood samples and single-cell flow cytometry. This study enrolled seroconverters and nonseroconverters after primovaccination (PV-PRNT(+) and PV-PRNT(-)), seroconverters after revaccination (RV-PRNT(+)), and unvaccinated volunteers (UV-PRNT(-)). Results. The analysis demonstrated in the PV-PRNT(+) group a balanced involvement of pro-inflammatory/regulatory adaptive immunity with a prominent participation of innate immunity pro-inflammatory events (IL-12(+) and TNF-alpha(+) NEU and MON). Using the PV-PRNT(+) cytokine signature as a reference profile, PV-PRNT(+) presented a striking lack of innate immunity proinflammatory response along with an increased adaptive regulatory profile (IL-4(+) CD4(+) T cells and IL-10(+) and IL-5(+) CD8(+) T cells). Conversely, the RV-PRNT(+) shifted the overall cytokine signatures toward an innate immunity pro-inflammatory profile and restored the adaptive regulatory response. Conclusions. The data demonstrated that the overall cytokine signature was associated with the levels of PRNT antibodies with a balanced innate/adaptive immunity with proinflammatory/regulatory profile as the hallmark of PV-PRNT(MEDIUM+), whereas a polarized regulatory response was observed in PV-PRNT(-) and a prominent proinflammatory signature was the characteristic of PV-PRNT(HIGH+).

The Stability of the Blood Oxygenation Level-Dependent Functional MRI Response to Motor Tasks Is Altered in Patients With Chronic Ischemic Stroke

Background and Purpose-Functional MRI is a powerful tool to investigate recovery of brain function in patients with stroke. An inherent assumption in functional MRI data analysis is that the blood oxygenation level-dependent (BOLD) signal is stable over the course of the examination. In this study, we evaluated the validity of such assumption in patients with chronic stroke. Methods-Fifteen patients performed a simple motor task with repeated epochs using the paretic and the unaffected hand in separate runs. The corresponding BOLD signal time courses were extracted from the primary and supplementary motor areas of both hemispheres. Statistical maps were obtained by the conventional General Linear Model and by a parametric General Linear Model. Results-Stable BOLD amplitude was observed when the task was executed with the unaffected hand. Conversely, the BOLD signal amplitude in both primary and supplementary motor areas was progressively attenuated in every patient when the task was executed with the paretic hand. The conventional General Linear Model analysis failed to detect brain activation during movement of the paretic hand. However, the proposed parametric General Linear Model corrected the misdetection problem and showed robust activation in both primary and supplementary motor areas. Conclusions-The use of data analysis tools that are built on the premise of a stable BOLD signal may lead to misdetection of functional regions and underestimation of brain activity in patients with stroke. The present data urge the use of caution when relying on the BOLD response as a marker of brain reorganization in patients with stroke. (Stroke. 2010; 41:1921-1926.)

Positive impact of omega-3 fatty acid supplementation in a dog with drug-resistant epilepsy: A case study

Epilepsy is the most common neurological disorder in both dogs and humans. Although the pharmacological options for treatment of epilepsies have increased. it has been reported that two-thirds of dogs with epilepsy are refractory to antiepileptic drug therapy. To our knowledge, there are no experimental Studies in the literature that show an effect of omega-3 supplementation oil epilepsy in dogs. Our case study describes the effectiveness of daily intake of a moderate amount of fish oil in a case of canine epilepsy. (C) 2009 Elsevier Inc. All rights reserved.

Effects of feeding high levels of cactus (Opuntia ficus-indica Mill) cladodes on urinary output and electrolyte excretion in goats

A study was conducted to determine the effects of feeding spineless cactus cladodes on diuresis and urinary electrolyte excretion in goats. Five bucks were used in a 5 x 5 Latin square experiment with 17-day periods. Experimental diets contained (g/kg dry matter (DM) basis) 370, 470, 570, 670, and 770 spineless cactus cladodes. Water consumption from feed and urine output increased linearly (P<0.05) as the level of cactus cladodes in the diet increased. However, water intake from drinking was low and unaffected by cactus cladode level. Creatinine clearance and urinary Na excretion were similar for all dietary treatments while K excretion decrease linearly (P<0.05) as the level of cactus cladodes in the diet increased. Feeding cactus cladodes caused diuresis and reduced urinary K excretion in goats. Possible reasons for these effects include water over-consumption from cactus cladodes and high dietary K intake. (C) 2007 Elsevier B.V. All rights reserved.