High prevalence of oral potentially malignant disorders and risk factors in a semi-urban brazilian city: a population-based cross-sectional study.

BACKGROUND: Oral Potentially Malignant Disorders (OPMDs) are defined as lesions with a greater likelihood of progressing to cancer. Population-based studies that evaluate the prevalence of OPMDs are scarce in Brazil. The aim of the present study was to determine the prevalence of OPMDs and associated risk factors in a semi-urban Brazilian population. MATERIAL AND METHODS: This is a cross-sectional study, whose universe included individuals aged 40 years or older residing in a medium-sized city of northeastern Brazil. Data collection was divided into two steps: interview and oral examination. The outcome variable was the presence of OPMDs. The predictor variables were sociodemographic characteristics and risk habits. The bivariate analysis was performed through chi-square test. The crude prevalence ratios (PR) and its respective 95% confidence intervals (CI) were calculated. Poisson regression analysis with robust variance was used to calculate adjusted PRs and 95% CI. RESULTS: Three hundred fourteen individuals were included in the study. When asked about risk habits, 58.9% reported being current smokers or ex-smokers and 62.2% reported being current drinkers or ex-drinkers. The prevalence of OPMDs was 7.6% and was significantly higher among individuals with black skin color (p < 0.001), alcohol users (p = 0.017), and individuals with both tobacco and alcohol habits (p = 0.012). CONCLUSIONS: Therefore, the population in the present study had a high frequency of risk habits associated with PMDs of the oral cavity.

HLA-DQB1 6672G>C (rs113332494) is associated with clozapine-induced neutropenia and agranulocytosis in individuals of European ancestry.

The atypical antipsychotic clozapine is the only effective medication for treatment-resistant schizophrenia. However, it can also induce serious adverse drug reactions, including agranulocytosis and neutropenia. The mechanism by which it does so is largely unknown, but there is evidence for contributing genetic factors. Several studies identified HLA-DQB1 variants and especially a polymorphism located in HLA-DQB1 (6672G>C, rs113332494) as associated with clozapine-induced agranulocytosis and neutropenia. We analysed the risk allele distribution of SNP rs113332494 in a sample of 1396 controls and 178 neutropenia cases of which 60 developed agranulocytosis. Absolute neutrophil counts of 500/mm3 and 1500/mm3 were used for defining agranulocytosis and neutropenia cases, respectively. We also performed association analyses and analysed local ancestry patterns in individuals of European ancestry, seeking replication and extension of earlier findings. HLA-DQB1 (6672G>C, rs113332494) was associated with neutropenia (OR = 6.20, P = 2.20E-06) and agranulocytosis (OR = 10.49, P = 1.83E-06) in individuals of European ancestry. The association signal strengthened after including local ancestry estimates (neutropenia: OR = 10.38, P = 6.05E-08; agranulocytosis: OR = 16.31, P = 1.39E-06), with effect sizes being considerably larger for agranulocytosis. Using local ancestry estimates for prediction, the sensitivity of rs113332494 increased from 11.28 to 55.64% for neutropenia and from 16.67 to 53.70% for agranulocytosis. Our study further strengthens the evidence implicating HLA-DQB1 in agranulocytosis and neutropenia, suggesting components of the immune system as contributing to this serious adverse drug reaction. Using local ancestry estimates might help in identifying risk variants and improve prediction of haematological adverse effects.

A case report of the successful administration of clozapine in the face of myocardial infarction, pulmonary embolism and hyperlipidaemia resulting in the termination of long-term seclusion.

BACKGROUND: Cardiometabolic health significantly impacts on the mortality of people with severe mental illness. Clozapine has the greatest efficacy for Treatment Resistant Schizophrenia (TRS) but the greatest negative impact on cardiometabolic health. Balancing the risks and benefits of treatment, dignity, autonomy, liberty, mental and physical health can be challenging, particularly when imposing interventions with potentially life threatening adverse events, such as clozapine. We describe the successful administration of clozapine in the face of myocardial infarction, pulmonary embolism and hyperlipidaemia resulting in the termination of long-term seclusion for a gentleman with TRS in high secure psychiatric services. CASE PRESENTATION: The impact of clozapine on a 44-year-old gentleman with TRS, extreme violence requiring physical restraint and long-term segregation, and numerous other significant physical health complications is described. He had metabolic syndrome; a poor diet, sedentary lifestyle, Body Mass Index (BMI) of 31.5, poorly controlled lipids and had smoked heavily since childhood. During preparations to initiate clozapine, he suffered a myocardial infarction and pulmonary embolism. His compliance with secondary prevention medications was poor due to paranoid persecutory and somatic delusions. Despite these concerns, nasogastric administration of clozapine was approved and prescribed within nine months of his myocardial infarction and a month from his pulmonary embolism but was ultimately not required. Accepting oral medication, his mental state made a rapid and dramatic improvement. After spending 1046 days in seclusion, this was terminated 94 days after clozapine initiation. He has been compliant with all medications for 24 months, had no incidents of violence or seclusion, and has been transferred to medium secure services. His physical health stabilised despite continuing to lead a sedentary lifestyle and remaining obese (BMI of 35). He developed hypertension, Type II Diabetes Mellitus and his triglycerides rose to 22.2 mmol/L in the same month after clozapine initiation. However, with pharmacological intervention, 24 months later these are controlled, and he has had no further thromboembolic events. CONCLUSIONS: We highlight that despite significant physical health concerns, clozapine can be successfully initiated and safely prescribed with a significantly positive effect on both the psychiatric and holistic care of patients with treatment resistant schizophrenia.

Tick, tock, lock: night-time confinement in high security - history, practice, ethics and practicalities.

SummaryNight-time confinement, locking patients in their bedrooms overnight, is practiced within high-secure hospitals in the UK. This article provides context, sets out the history and reviews the ethical and pragmatic issues at stake. Thought is given to the future, where we appear to be moving toward a different approach.Declaration of interestE.S. is a consultant forensic psychiatrist at Ashworth Hospital. All his patients are confined at night. He represents the Royal College of Psychiatrists Forensic Faculty at the National Oversight Group, which is the strategic advisory body providing assurance to NHS England regarding the commissioning and provision of high-secure services.

El virus del Zika. Un agente teratogénico ocular / Zika virus. A teratogenic agent for the eyes

No disponible

Cross neutralization of coral snake venoms by commercial Australian snake antivenoms.

CONTEXT: Although rare, coral snake envenomation is a serious health threat in Brazil, because of the highly neurotoxic venom and the scarcely available antivenom. The major bottleneck for antivenom production is the low availability of venom. Furthermore, the available serum is not effective against all coral snake species found in Brazil. An alternative to circumvent the lack of venom for serum production and the restricted protection of the actually available antivenom would be of great value. We compared the Brazilian coral snake and mono and polyvalent Australian antivenoms in terms of reactivity and protection. METHODS: The immunoreactivity of venoms from 9 coral snakes species were assayed by ELISA and western blot using the Brazilian Micrurus and the Australian pentavalent as well as monovalent anti-Notechis, Oxyuranus and Pseudechis antivenoms. Neutralization assays were performed in mice, using 3 LD50 of the venoms, incubated for 30 minutes with 100 µL of antivenom/animal. DISCUSSION: All the venoms reacted against the autologous and heterologous antivenoms. Nevertheless, the neutralization assays showed that the coral snake antivenom was only effective against M. corallinus, M. frontalis, M. fulvius, M. nigrocinctus and M. pyrrhocryptus venoms. On the other hand, the Australian pentavalent antivenom neutralized all venoms except the one from M. spixii. A combination of anti-Oxyuranus and Pseudechis monovalent sera, extended the protection to M. altirostris and, partially, to M. ibiboboca. By adding Notechis antivenom to this mixture, we obtained full protection against M. ibiboboca and partial neutralization against M. lemniscatus venoms. CONCLUSIONS: Our findings confirm the limited effectiveness of the Brazilian coral snake antivenom and indicate that antivenoms made from Australian snakes venoms are an effective alternative for coral snake bites in South America and also in the United States were coral snake antivenom production has been discontinued.

Cross neutralization of coral snake venoms by commercial Australian snake antivenoms

Context: Although rare, coral snake envenomation is a serious health threat in Brazil, because of the highly neurotoxic venom and the scarcely available antivenom. The major bottleneck for antivenom production is the low availability of venom. Furthermore, the available serum is not effective against all coral snake species found in Brazil. An alternative to circumvent the lack of venom for serum production and the restricted protection of the actually available antivenom would be of great value. We compared the Brazilian coral snake and mono and polyvalent Australian antivenoms in terms of reactivity and protection. Methods: The immunoreactivity of venoms from 9 coral snakes species were assayed by ELISA and western blot using the Brazilian Micrurus and the Australian pentavalent as well as monovalent antiNotechis, Oxyuranus and Pseudechis antivenoms. Neutralization assays were performed in mice, using 3 LD50 of the venoms, incubated for 30 minutes with 100 mu L of antivenom/animal. Discussion: All the venoms reacted against the autologous and heterologous antivenoms. Nevertheless, the neutralization assays showed that the coral snake antivenom was only effective against M. corallinus, M. frontalis, M. fulvius, M. nigrocinctus and M. pyrrhocryptus venoms. On the other hand, the Australian pentavalent antivenom neutralized all venoms except the one from M. spixii. A combination of anti-Oxyuranus and Pseudechis monovalent sera, extended the protection to M. altirostris and, partially, to M. ibiboboca. By adding Notechis antivenom to this mixture, we obtained full protection against M. ibiboboca and partial neutralization against M. lemniscatus venoms. Conclusions: Our findings confirm the limited effectiveness of the Brazilian coral snake antivenom and indicate that antivenoms made from Australian snakes venoms are an effective alternative for coral snake bites in South America and also in the United States were coral snake antivenom production has been discontinued.

Ciliopatías y su relación con la oftalmología / The ciliopathies and their relationship with ophthalmology

No disponible

Reversal of the anticoagulant and anti-hemostatic effect of low molecular weight heparin by direct prothrombin activation

Lopap, found in the bristles of Lonomia obliqua caterpillar, is the first exogenous prothrombin activator that shows serine protease-like activity, independent of prothrombinase components and unique lipocalin reported to interfere with hemostasis mechanisms. To assess the action of an exogenous prothrombin activator reversing the anticoagulant and antihemostatic effect induced by low molecular weight heparin (LMWH), male New Zealand rabbits (N = 20, weighing 3.8-4.0 kg) allocated to 4 groups were anticoagulated with 1800 IU/kg LMWH (iv) over 2 min, followed by iv administration of saline (SG) or recombinant Lopap (rLopap) at 1 µg/kg (LG1) or 10 µg/kg (LG10), 10 min after the injection of LMWH, in a blind manner. Control animals (CG) were treated only with saline. The action of rLopap was assessed in terms of activated partial thromboplastin time (aPTT), prothrombin fragment F1+2, fibrinogen, and ear puncture bleeding time (BT) at 5, 10, 15, 17, 20, 30, 40, 60, and 90 min after initiation of LMWH infusion. LG10 animals showed a decrease of aPTT in more than 50% and BT near to normal baseline. The level of prothrombin fragment F1+2 measured by ELISA had a 6-fold increase with rLopap treatment (10 µg/kg) and was inversely proportional to BT in LMWH-treated animals. Thus, Lopap, obtained in recombinant form using E. coli expression system, was useful in antagonizing the effect of LMWH through direct prothrombin activation, which can be a possible strategy for the reversal of bleeding and anticoagulant events.