Efficacy of andrographolide in not active progressive multiple sclerosis: a prospective exploratory double-blind, parallel-group, randomized, placebo-controlled trial.

BACKGROUND: Multiple sclerosis (MS) is a chronic immune mediated disease and the progressive phase appears to have significant neurodegenerative mechanisms. The classification of the course of progressive MS (PMS) has been re-organized into categories of active vs. not active inflammatory disease and the presence vs. absence of gradual disease progression. Clinical trial experience to date in PMS with anti-inflammatory medications has shown limited effect. Andrographolide is a new class of anti-inflammatory agent, that has been proposed as a potential drug for autoimmune disorders, including MS. In the present trial, we perform an exploratory pilot study on the efficacy and safety of andrographolide (AP) compared to placebo in not active PMS. METHODS: A pilot clinical trial using 140 mg oral AP or placebo twice daily for 24 months in patients with not active primary or secondary progressive MS was conducted. The primary efficacy endpoint was the mean percentage brain volume change (mPBVC). Secondary efficacy endpoints included 3-month confirmed disability progression (3-CDP) and mean EDSS change. RESULTS: Forty-four patients were randomized: 23 were assigned to the AP group, and 21 were assigned to the placebo group. The median baseline EDSS of both groups was 6.0. Annualized mPBVC was - 0.679% for the AP group and - 1.069% for the placebo group (mean difference: -0.39; 95% CI [- 0.836-0.055], p = 0.08, relative reduction: 36.5%). In the AP group, 30% had 3-CDP compared to 41% in the placebo group (HR: 0.596; 95% CI [0.200-1.777], p = 0.06). The mean EDSS change was - 0.025 in the AP group and + 0.352 in the placebo group (mean difference: 0.63, p = 0.042). Adverse events related to AP were mild rash and dysgeusia. CONCLUSIONS: AP was well tolerated and showed a potential effect in reducing brain atrophy and disability progression, that need to be further evaluated in a larger clinical trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT02273635 retrospectively registered on October 24th, 2014.

Double Heterozygosity for Hb Durham-N.C. (HBB: c.344T>C) [ß114(G16)Leu→Pro] and the IVS-I-110 (HBB: c.93-21G>A) Causing a Severe ß-Thalassemia Phenotype.

The evaluation of a 10-month-old girl of Sicilian origin with a clinical phenotype of severe thalassemia led to the identification of two ß-globin gene defects, a ß-thalassemia (ß-thal), mutation at IVS-I-110 (HBB: c.93-21G>A) and a variant hemoglobin (Hb) mutation at codon 114 (HBB: c.344T>C) on the other allele, reported as Hb Durham-N.C. (also known as Hb Brescia) [ß114(G16)Leu→Pro] in the HbVar database. A very low Hb level (Hb 3.5 g/dL), microcytosis [mean corpuscular volume (MCV) 63.2 fL] and hypocromia [mean corpuscular Hb (MCH) 19.6 pg], increased red blood cell (RBC) distribution width (RDW) (36.0%), higher reticulocytes (6.2%), anisocytosis, poikilocytosis, hypocromia, basophilic stippling and inclusion body formation, were present in the affected subject. Analysis of other family components showed the presence of HBB: c.93-21G>A defect in the mother and in her brother, while Hb Durham-N.C. was absent in all other relatives, thus, this mutation has arisen as a de novo defect. This is the first case described as a severe thalassemic phenotype in a compound heterozygote carrier of this unstable Hb and a common ß-thalassemic allele. The important information gained from this case is that a rare dominant or recessive mutation may arise in every individual, even if this is a very rare event.

Editorial: Looked-after children - a perspective into a more resilient future.

Looked after children (LAC) are among the most vulnerable group in our society in terms of their risk of a range of poor outcomes including mental health, educational attainments and social wellbeing. Over the past decade, it has become increasingly clear that LAC have a higher prevalence of mental health problems than the general population, including children living with their families in "high-risk" populations. These children present with high rates of, both emotional and behavioural problems, and also neurodevelopmental problems. This Editorial highlights a collection of 10 articles and accompanying Introduction for a Virtual Issue on LAC, published as a free resource at: http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1475-3588/homepage/LAC.htm.

Introduction: Looked-after children.

Looked-after children (LAC) (also known as children in care) are among the most vulnerable group in our society. This is in terms of their risk of a range of poor outcomes including mental health, educational attainment and social wellbeing (Meltzer, Gatward, Corbin, Goodman, & Ford, 2003). Over the past decade, it has become increasingly clear that LAC have a higher prevalence of mental health problems than the general population, including children living with their families in 'high-risk' populations. These children present with high rates of, not only emotional and behavioural problems, but also neurodevelopmental problems. The present Virtual Issue focusing on the mental health of this group of young people brings together research published in CAMH over the past 15 years.

Double screening for syphilis and HIV in pregnant women in a priority municipality for the elimination of vertical transmission in Brazil: incidence, risk factors and spatial analysis.

BACKGROUND: The Brazilian Ministry of Health (MoH) recommends double screening (DS) for syphilis and HIV during the first and third trimesters of antenatal care (ANC) to mitigate vertical transmission. We surveyed DS outcomes and their associated factors in a priority Brazilian municipality with >100 000 inhabitants who face challenges for both health problems. METHODS: A total of 399 women were followed up throughout pregnancy using medical records. Spatial and multinomial logistic analyses were performed. RESULTS: There was an incidence rate of 24.8%, 59.4% and 15.8% for 'full DS', 'partial DS' and 'without DS', respectively. Younger women and those with a history of both prematurity and multiparity were less likely to be in the 'full DS' category. There was an overlap of high-density clusters of 'full DS' and 'ANC in better quality basic health units', adherent to both the Family Health Strategy and the National Program for Access and Quality Improvement in Primary Care. CONCLUSIONS: The poor DS outcomes presented in 75% of the cases were mostly linked to delays in starting ANC appointments or their discontinuity. Thus, the MoH recommendations, accompanied by ongoing training, technical assistance and the periodic evaluation of their implementation, need to effectively reach providers and promote counseling and awareness about the importance of DS for pregnant women.

Analysis of anti-tuberculosis drug resistance and sociodemographic and clinical aspects of patients admitted in a referral hospital.

OBJECTIVE: To determine the occurrence of anti-tuberculosis drug resistance and its association with sociodemographic and clinical characteristics of patients in a referral hospital. METHODS: This was a cross-sectional study based on data from patients who had mycobacterial culture identified and defined antimicrobials sensitivity profile (June 2014 to February 2016). The descriptive statistical analysis and Fisher's exact test were used to compare proportions. RESULTS: The study included 104 patients who had positive results for Mycobacterium tuberculosis . Bacilloscopy had high positivity (93.3%). A total of 15 patients (14.4%) had resistant strains and six (5.6%) multidrug-resistant. The sociodemographic and clinical characteristics were not related with resistance. CONCLUSION: This study contributed to further the understandings about the tuberculosis patients' profile, the study also served as a tool for development of specific public policies. Patients diagnosed with resistant tuberculosis must be under greater supervision.

Comparison between Ogawa-Kudoh and modified Petroff techniques for mycobacteria cultivation in the diagnosis of pulmonary tuberculosis.

OBJECTIVE: To compare the performance of the Ogawa-Kudoh method with the modified Petroff technique in diagnosis of pulmonary tuberculosis. METHODS: A total of 205 sputum samples from 166 patients with clinical suspicion or under pulmonary tuberculosis follow-up, seen at a public tertiary care hospital, from July 2014 to July 2016 were used. All samples were simultaneously processed using the Ogawa-Kudoh and modified Petroff decontamination methods, according to the recommendations of the Ministry of Health. In the statistical analysis, the McNemar test and the Kappa index were used, respectively, to compare proportions and verify agreement between data. RESULTS: The Ogawa-Kudoh and modified Petroff methods were efficient in mycobacteria detection, with no significant differences in results (p=0.549) and contamination rate of the cultures (p=0.065). The agreement between techniques was considered excellent (Kappa index of 0.877) and Ogawa-Kudoh, as compared to the modified Petroff technique, showed sensitivity of 90.4%, specificity of 96.6%, positive predictive value of 94.3% and negative predictive value of 94.2%. CONCLUSION: The Ogawa-Kudoh technique proved to be sufficiently sensitive and specific for diagnosis of pulmonary tuberculosis, and, therefore, suitable for routine laboratory application. Since it is simple, low-cost and has less technical requirements for biosafety and professional training, Ogawa-Kudoh is an alternative for managers and healthcare professionals to promote the expansion of bacteriological diagnostic coverage of pulmonary tuberculosis.

ADHD and infant disorganized attachment: a prospective study of children next-born after stillbirth.

OBJECTIVE: To examine whether infant disorganized attachment predicts ADHD at school age. METHOD: A cohort of 53 children who had been identified as having significant levels of disorganized attachment in infancy is compared to a control group. Symptoms and signs of ADHD at age 7 are evaluated together with a range of relevant maternal variables. RESULTS: An association is found between infant disorganized attachment scores and teacher-rated symptoms of ADHD (but not ADHD caseness). Probable ADHD caseness in the child is associated with self-rated retrospective ADHD scores in mothers. Possible ADHD caseness is associated with a measure of unresolved mourning in mothers. Mother-rated ADHD in the child was associated with low overall maternal psychosocial functioning. CONCLUSION: The finding of a link between scores for disorganized attachment at 1 year and later teacher-rated symptoms of ADHD suggests the need for further studies.

Analysis of anti-tuberculosis drug resistance and sociodemographic and clinical aspects of patients admitted in a referral hospital / Análise da resistência a medicamentos antituberculose e aspectos sociodemográficos e clínicos de pacientes atendidos em hospital referência

ABSTRACT Objective To determine the occurrence of anti-tuberculosis drug resistance and its association with sociodemographic and clinical characteristics of patients in a referral hospital. Methods This was a cross-sectional study based on data from patients who had mycobacterial culture identified and defined antimicrobials sensitivity profile (June 2014 to February 2016). The descriptive statistical analysis and Fisher's exact test were used to compare proportions. Results The study included 104 patients who had positive results for Mycobacterium tuberculosis . Bacilloscopy had high positivity (93.3%). A total of 15 patients (14.4%) had resistant strains and six (5.6%) multidrug-resistant. The sociodemographic and clinical characteristics were not related with resistance. Conclusion This study contributed to further the understandings about the tuberculosis patients' profile, the study also served as a tool for development of specific public policies. Patients diagnosed with resistant tuberculosis must be under greater supervision.

RESUMO Objetivo Verificar a ocorrência de resistência a fármacos antituberculose e a associação com características sociodemográficas e clínicas de pacientes de um hospital referência. Métodos Estudo transversal, com dados de pacientes que tiveram a cultura de micobactérias identificada e o respectivo perfil de sensibilidade aos antimicrobianos definido (junho de 2014 a fevereiro de 2016). Foram realizados a análise estatística descritiva e o teste exato de Fisher, para comparação de proporções. Resultados O estudo envolveu 104 pacientes, e todos tiveram resultados para Mycobacterium tuberculosis . A baciloscopia atingiu alta positividade (93,3%), e 15 pacientes (14,4%) apresentaram linhagens resistentes, sendo 6 (5,6%) multirresistentes. As características sociodemográficas e clínicas não foram associadas à resistência. Conclusão A pesquisa permitiu conhecer melhor o perfil dos pacientes com tuberculose e constitui ferramenta para elaboração de políticas públicas específicas. Os pacientes diagnosticados com tuberculose resistente devem ser submetidos à maior supervisão.

Xanthohumol, a prenylated flavonoid from hops (Humulus lupulus L.), protects rat tissues against oxidative damage after acute ethanol administration.

Ethanol-mediated free radical generation is directly involved in alcoholic liver disease. In addition, chronic alcohol bingeing also induces pathological changes and dysfunction in multi-organs. In the present study, the protective effect of xanthohumol (XN) on ethanol-induced damage was evaluated by determining antioxidative parameters and stress oxidative markers in liver, kidney, lung, heart and brain of rats. An acute treatment (4 g/kg b.w.) of ethanol resulted in the depletion of superoxide dismutase, catalase and glutathione S-transferase activities and reduced glutathione content. This effect was accompanied by the increased activity of tissue damage marker enzymes (glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and lactate dehydrogenase) and a significant increase in lipid peroxidation and hydrogen peroxide concentrations. Pre-treatment with XN protected rat tissues from ethanol-induced oxidative imbalance and partially mitigated the levels to nearly normal levels in all tissues checked. This effect was dose dependent, suggesting that XN reduces stress oxidative and protects rat tissues from alcohol-induced injury.

Comparison between Ogawa-Kudoh and modified Petroff techniques for mycobacteria cultivation in the diagnosis of pulmonary tuberculosis / Comparação entre os métodos de Ogawa-Kudoh e Petroff modificado para o cultivo de micobactérias no diagnóstico da tuberculose pulmonar

ABSTRACT Objective To compare the performance of the Ogawa-Kudoh method with the modified Petroff technique in diagnosis of pulmonary tuberculosis. Methods A total of 205 sputum samples from 166 patients with clinical suspicion or under pulmonary tuberculosis follow-up, seen at a public tertiary care hospital, from July 2014 to July 2016 were used. All samples were simultaneously processed using the Ogawa-Kudoh and modified Petroff decontamination methods, according to the recommendations of the Ministry of Health. In the statistical analysis, the McNemar test and the Kappa index were used, respectively, to compare proportions and verify agreement between data. Results The Ogawa-Kudoh and modified Petroff methods were efficient in mycobacteria detection, with no significant differences in results (p=0.549) and contamination rate of the cultures (p=0.065). The agreement between techniques was considered excellent (Kappa index of 0.877) and Ogawa-Kudoh, as compared to the modified Petroff technique, showed sensitivity of 90.4%, specificity of 96.6%, positive predictive value of 94.3% and negative predictive value of 94.2%. Conclusion The Ogawa-Kudoh technique proved to be sufficiently sensitive and specific for diagnosis of pulmonary tuberculosis, and, therefore, suitable for routine laboratory application. Since it is simple, low-cost and has less technical requirements for biosafety and professional training, Ogawa-Kudoh is an alternative for managers and healthcare professionals to promote the expansion of bacteriological diagnostic coverage of pulmonary tuberculosis.

RESUMO Objetivo Comparar o desempenho do método de Ogawa-Kudoh ao de Petroff modificado no diagnóstico da tuberculose pulmonar. Métodos Utilizaram-se 205 amostras de escarro de 166 pacientes com suspeita clínica ou controle de tuberculose pulmonar atendidos em um hospital público terciário, entre os meses de julho de 2014 a julho de 2016. Todas as amostras foram processadas simultaneamente pelos métodos de descontaminação Ogawa-Kudoh e Petroff modificado, seguindo as recomendações do Ministério da Saúde. Na análise estatística, foi empregado o teste de McNemar, para comparação de proporções, e o índice Kappa, para verificar o grau de concordância entre os dados. Resultados Os métodos Ogawa-Kudoh e Petroff modificado mostraram-se eficientes na detecção de micobactérias, não sendo verificadas discordâncias significativas tanto nas comparações de pares de resultados (p=0,549), como na taxa de contaminação das culturas (p=0,065). O grau de concordância das técnicas foi considerado excelente (índice Kappa de 0,877), e o Ogawa-Kudoh, em relação ao Petroff modificado, apresentou 90,4% de sensibilidade, 96,6% de especificidade, 94,3% de valor preditivo positivo e 94,2% de valor preditivo negativo. Conclusão O método de Ogawa-Kudoh revelou-se suficientemente sensível e específico para o diagnóstico da tuberculose pulmonar e, portanto, adequado para a aplicação na rotina laboratorial. Por ser mais simples, de baixo custo e com menores exigências técnicas de biossegurança e capacitação profissional, o Ogawa-Kudoh apresenta-se como alternativa para gestores e profissionais da área promoverem a ampliação da cobertura diagnóstica bacteriológica da tuberculose pulmonar.

Xanthohumol prevents carbon tetrachloride-induced acute liver injury in rats.

Xanthohumol (XN), a prenyl flavonoid present in beer, prevents the acute hepatic injury induced by carbon tetrachloride (CCl4) in rats. Pre-treatment of rats with XN significantly reduced the increased liver weight observed in CCl4-intoxicated rats, normalised the increased values of plasma lactate dehydrogenase, glutamate oxaloacetate transaminase and glutamate pyruvate transaminase activities and reduced the incidence of histopathological alterations produced by CCl4. The oxidative stress induced by CCl4 administration elicited a significant decrease in the levels of reduced glutathione as well as an increase in thiobarbituric acid reactive substances (TBARS) and H2O2 concentrations. Pre-treatment of rats with XN resulted in a significant (p<0.05) increase in reduced glutathione (GSH) content and a reduction in TBARS and H2O2 concentrations to their normal values. XN pre-treatment also prevented the significant reductions of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase activities observed in CCl4-treated rats compared to control animals. Our results suggest that the hepatoprotective effect of XN is based on its antioxidant properties as well as it being an efficient inhibitor of lipid peroxidation and a protector against the degradation of antioxidant enzymes induced by CCl4 intoxication.

Use of psychotropics among looked after children: an audit in the Borough of Lambeth.

Background Looked after children and young people (LAC) have higher incidence of mental health problems than non-looked after children. Many mental health difficulties are missed in this group, in particular the effects of trauma and loss and the resulting depression. LAC often move between placements, which further disrupts their care and therapeutic interventions. NICE recommends that in most mental health disorders, children and adolescents should receive specific psychological therapies as first-line treatment, before medication. This standard should apply to LAC. Setting The audit was conducted in the Lambeth CLAMHS, a specialist mental health team working with LAC. Question To ascertain if Lambeth LAC (living in the borough) are receiving psychotropic medication without CLAMHS input and as their only treatment. (All LAC who are on psychotropic medication should have been offered psychological treatments first.) Methods A questionnaire was sent out to Lambeth general practice (GP) surgeries to find out what medications children were prescribed, if any. When children were prescribed psychotropic medication checks were made to ascertain whether they were receiving input from mental health services. Results LAC were seen in 67 different GP surgeries across Lambeth. Responses from 63 surgeries relating to 145 children (87.34% of the total number) were received. Conclusions There were no LAC in Lambeth who were prescribed psychotropic medication without a CAMHS service being involved. All the patients that were on psychotropic medication were known by CLAMHS or another child and adolescent mental health service within the South London and Maudsley NHS Foundation Trust. This is in accordance with NICE recommendations.

Acquired and inherited thrombophilia in women with unexplained fetal losses.

OBJECTIVE: The purpose of this study was to investigate the possible role of inherited and acquired thrombophilia in women with unexplained abortions and intrauterine fetal death. STUDY DESIGN: We included 75 women with >/=1 unexplained fetal loss, and 75 control subjects with at least 1 healthy term infant and without gestational complications. All of these women were tested for mutations of factor V Leiden, methylenetetrahydrofolate reductase, and prothrombin gene; deficiencies of antithrombin-III, protein C, and protein S; and the presence of antiphospholipid antibodies and fasting homocysteine concentration. A placental histologic study was also carried out. RESULTS: Thirty-five percent of the 75 patients had thrombophilia (control subjects, 16%; P =.008; odds ratio, 2.78). This prevalence was more prominent in second and third trimesters (P =.0002; odds ratio, 6.3), and the presence of combined genetic defects was associated with intrauterine fetal death (P =.04; odds ratio, 12; 95% CI, 1.44-102). When we analyzed the overall gestations of the patients, we observed an increase of intrauterine fetal death in patients with thrombophilia (P =.01) and early pregnancy loss in patients without thrombophilia (P =.02). The analysis of the correlation between extensive placental infarctions and thrombophilic defects rendered values in the boundaries of significance (P =.05). CONCLUSION: The significant high prevalence of biologic causes in patients with late fetal loss suggests that a study of thrombophilia should be carried out, together with an assessment of a preventive treatment.

Leucemia "cutis" / Leukemia cutis

A pele pode mostrar vários sinais de doenças internas. Nas leucemias, lesões cutâneas podem estar associadas à doença sistêmica. Relatamos um caso de leucemia monocítica aguda com leukemia cutis.

The skin can show signs of internal disease. In leukemia, cutaneous lesions can be associated with systemic disease. We report a case of acute monocytic leukemia with leukemia cutis.