Warfarin Hipersensitivity. How to Deal with it?

Os autores descrevem um caso clínico de hipersensibilidade à varfarina traduzido por uma elevação acentuada do INR, aquando da introdução do fármaco em doente com antecedentes tromboembólicos. Da pesquisa de polimorfismos para os genes VKORC1 e CYP2C9, utilizando técnicas de amplificação por PCR e hibridização reversa, apurou-se heterozigotia para -1639G>A (gene VKORC1) e homozigotia para 1075A>C (genótipo CYP2C9*3/*3). Os autores fazem uma revisão da farmacodinâmica da varfarina e da sua acção sobre a vitamina K, sugerindo-se indicações para a investigação de algumas variações genéticas, no sentido de obviar potenciais complicações associadas ao fármaco

An accurate test for homogeneity of odds ratios based on Cochran's Q-statistic

Background: A frequently used statistic for testing homogeneity in a meta-analysis of K independent studies is Cochran's Q. For a standard test of homogeneity the Q statistic is referred to a chi-square distribution with K - 1 degrees of freedom. For the situation in which the effects of the studies are logarithms of odds ratios, the chi-square distribution is much too conservative for moderate size studies, although it may be asymptotically correct as the individual studies become large. Methods: Using a mixture of theoretical results and simulations, we provide formulas to estimate the shape and scale parameters of a gamma distribution to t the distribution of Q. Results: Simulation studies show that the gamma distribution is a good approximation to the distribution for Q. Conclusions: : Use of the gamma distribution instead of the chi-square distribution for Q should eliminate inaccurate inferences in assessing homogeneity in a meta-analysis. (A computer program for implementing this test is provided.) This hypothesis test is competitive with the Breslow-Day test both in accuracy of level and in power

Anti-inflammatory, anti-proliferative and antioxidant profiles of selective cyclooxygenase-2 inhibition as chemoprevention for rat bladder carcinogenesis

PURPOSE: To evaluate the efficacy of a selective cyclooxygenase-2 (COX-2) inhibitor in rat bladder cancer chemoprevention, as well as to assess the relevance of inflammation, proliferation and oxidative stress in tumor growth and in its prevention. RESULTS: The main findings were: (I) the incidence of carcinoma was: control: 0% (0/8); BBN: 65% (13/20); CEL: 0% (0/8) and BBN + CEL: 12.5% (1/8); (II) the mean tumor volume per rat with tumor and per tumor were significantly lower in the BBN + CEL group (21.2 and 5.3 +/- 0.4 mm(3)) vs. BBN (138.5 +/- 7.5 and 112.5 +/- 6.4 mm(3)); (III) the incidence of pre-neoplasic (hyperplasia and dysplasia) and neoplasic (papillary tumors and carcinoma in situ-CIS) lesions were notoriously reduced in the CEL + BBN treatment; (IV) CEL significantly reduced serum TGFbeta1 and CRP and increase TNFalpha and IL-1beta (p < 0.001); (V) CEL reduced MDA formation in serum (p < 0.001) and liver (p < 0.05) and also showed a trend to reduction in kidney. METHODS: Drug treatments were performed during the first 8 w, followed by 12 w for tumor expression/prevention, in the following groups: control-vehicle; carcinogen-0.05% of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN); celecoxib (CEL)-10 mg/kg/day and preventive CEL + BBN. The bladders were analyzed for number and volume of tumor and nature of urothelium lesions. Serum was assessed for markers of inflammation, proliferation and redox status. CONCLUSIONS: Celecoxib has demonstrated an outstanding inhibitory effect on bladder cancer chemoprevention, which might be due to its expected anti-inflammatory actions, as well as by anti-proliferatory and antioxidant actions. This data supports a pivotal role of cancer chemoprevention strategies based on COX-2 inhibition

Degradation studies of hydrophilic, partially degradable and bioactive cements (HDBCs) incorporating chemically modified starch

The degradation rate in Hydrophilic, Degradable and Bioactive Cements (HDBCs) containing starch/cellulose acetate blends (SCA) is still low. In order to increase degradation, higher amounts of starch are required to exceed the percolation threshold. In this work, gelatinization, acetylation and methacrylation of corn starch were performed and assessed as candidates to replace SCA in HDBCs. Formulations containing methacrylated starch were prepared with different molar ratios of 2-hydroxyethyl methacrylate and methyl methacrylate in the liquid component and the amount of residual monomer released into water was evaluated. The concentration of reducing sugars, percentage of weight loss and morphologic analyses after degradation all confirmed increased degradation of HDBC with alpha-amylase, with the appearance of pores and voids from enzymatic action. Methacrylated starch therefore is a better alternative to be used as the solid component of HDBC then SCA, since it leads to the formation of cements with a lower release of toxic monomers and more prone to hydrolytic degradation while keeping the other advantages of HDBCs.The authors acknowledge to Foundation for Science and Technology (FCT), who supported this study through funds from project Concept2Cement (POCTI/CTM/60735/2004)

The conservation value of human-modified landscapes for the world's primates

Land-use change pushes biodiversity into human-modified landscapes, where native ecosystems are surrounded by anthropic land covers (ALCs). Yet, the ability of species to use these emerging covers remains poorly understood. We quantified the use of ALCs by primates worldwide, and analyzed species' attributes that predict such use. Most species use secondary forests and tree plantations, while only few use human settlements. ALCs are used for foraging by at least 86 species with an important conservation outcome: those that tolerate heavily modified ALCs are 26% more likely to have stable or increasing populations than the global average for all primates. There is no phylogenetic signal in ALCs use. Compared to all primates on Earth, species using ALCs are less often threatened with extinction, but more often diurnal, medium or large-bodied, not strictly arboreal, and habitat generalists. These findings provide valuable quantitative information for improving management practices for primate conservation worldwide

Ganho de peso, dislipidemia e parâmetros alterados para síndrome metabólica em pacientes de primeiro episódio psicótico após seguimento de seis meses

OBJECTIVES: Obesity and metabolic abnormalities are frequent in psychotic patients, including first-episode psychosis. We evaluated weight and metabolic parameters in first-episode psychotic outpatients from the First Episode Psychosis Program, Universidade Federal de São Paulo (UNIFESP). METHOD: Weight, height, waist and hip circumferences, glucose and lipid levels were measured at baseline and after a six-month period. RESULTS: Fifty-seven patients were included and 44 (77.2%) of them finished the study. Patients had a median age of 26.3 years, 60% were men and 43% had a diagnosis of schizophrenia at the endpoint. Weight and BMI values increased significantly during the follow-up (p < 0.01). The average weight gain at the follow-up was 10.1% of the baseline weight (SD = 11.9). Only women presented significant waist abnormalities: at the first assessment the waist mean was 79.12 cm (SD = 10.68) and 6 months later it had increased to 89.65 cm (SD = 11.19, z = -3.182, p = 0.001). After 6 months, the total cholesterol (p = 0.004), and triglyceride levels (p = 0.016) increased, while HDL-cholesterol levels decreased (p = 0.025). During the follow-up period one patient (2.3%) developed diabetes mellitus, one (2.3%) presented altered fasting glucose, 12 (27.2%) patients developed at least two altered parameters for metabolic syndrome and 3 (6.8%) patients developed metabolic syndrome (p = 0.001). DISCUSSION: The results of this study showed that in a short period of time individuals under antipsychotic treatment had their weight increased significantly and developed important metabolic abnormalities. CONCLUSIONS: Clinicians should be aware of these risks, choose an antipsychotic that causes less weight gain and should monitor these patients carefully, and recommend prophylactic measures as diet restriction and physical activities.OBJETIVOS: Obesidade e alterações metabólicas são freqüentes em pacientes psicóticos, inclusive no primeiro episódio psicótico. Foram avaliados peso e parâmetros metabólicos em pacientes em tratamento no Programa de Episódio Psicótico da Universidade Federal de São Paulo (UNIFESP). MÉTODO: Peso, altura, medida de cintura e quadril, glicemia e perfil lipídico foram avaliados no início do tratamento e após seis meses. RESULTADOS: Cinqüenta e sete pacientes foram incluídos no estudo e 44 (72%) concluíram o estudo. Os pacientes apresentavam em média 26,3 anos, 60% eram do sexo masculino e, ao final do estudo, 43% apresentavam diagnóstico de esquizofrenia. Houve aumento significativo do peso e índice de massa corporal durante o estudo (p < 0,01). Em média, o peso aumentou 10,1% do peso inicial (SD = 11,9). Apenas mulheres apresentaram alterações na medida da cintura: no início, a média da cintura era de 79,12 cm (SD = 10,68) e, após seis meses, houve um aumento para 89,65 cm (SD = 11,19, z = -3,182, p = 0,001). Após seis meses, houve aumento do colesterol total (p = 0,004) e triglicérides (p = 0,016), e diminuição dos níveis de colesterol HDL (p = 0,025). No período, um paciente (2,3%) desenvolveu diabetes mellitus, um paciente (2,3%) apresentou glicemia de jejum alterada, 12 (27,2%) desenvolveram pelo menos dois parâmetros alterados para síndrome metabólica, e 3 (6,8%) apresentaram síndrome metabólica (p = 0,001). DISCUSSÃO: Os resultados deste estudo mostram que em um curto período de tempo pacientes em tratamento com antipsicóticos aumentaram substancialmente o peso e desenvolveram importantes alterações metabólicas. CONCLUSÃO: Os clínicos devem estar atentos a esses riscos, escolher medicações que causem menor ganho de peso, devendo monitorar esses pacientes cuidadosamente e recomendar medidas profiláticas como restrição dietética e atividade física.Universidade Federal de São Paulo (UNIFESP) Department of Psychiatry First-episode Psychosis ProgramUNIFESP, Department of Psychiatry First-episode Psychosis ProgramSciEL

Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB)

BACKGROUND:Cutaneous leishmaniasis (CL) is a neglected tropical disease caused by protozoan parasites of the genus Leishmania. CL causes enormous suffering in many countries worldwide. There is no licensed vaccine against CL, and the chemotherapy options show limited efficacy and high toxicity. Localization of the parasites inside host cells is a barrier to most standard chemo- and immune-based interventions. Hence, novel drugs, which are safe, effective and readily accessible to third-world countries and/or drug delivery technologies for effective CL treatments are desperately needed. METHODOLOGY/PRINCIPAL FINDINGS:Here we evaluated the antileishmanial properties and delivery potential of polyhexamethylene biguanide (PHMB; polyhexanide), a widely used antimicrobial and wound antiseptic, in the Leishmania model. PHMB showed an inherent antileishmanial activity at submicromolar concentrations. Our data revealed that PHMB kills Leishmania major (L. major) via a dual mechanism involving disruption of membrane integrity and selective chromosome condensation and damage. PHMB's DNA binding and host cell entry properties were further exploited to improve the delivery and immunomodulatory activities of unmethylated cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN). PHMB spontaneously bound CpG ODN, forming stable nanopolyplexes that enhanced uptake of CpG ODN, potentiated antimicrobial killing and reduced host cell toxicity of PHMB. CONCLUSIONS:Given its low cost and long history of safe topical use, PHMB holds promise as a drug for CL therapy and delivery vehicle for nucleic acid immunomodulators

Possible association between ABCC8 C49620T polymorphism and type 2 diabetes in a Nigerian population

The association between ABCC8 gene C49620T polymorphism and type 2 diabetes (T2D) in populations of diverse ethnic backgrounds has been reported. However, such occurrence in an African population is yet to be established. This case-control study involving 73 T2D and 75 non-diabetic (ND) patients investigated the occurrence of this polymorphism among T2D patients in Nigeria and assessed its relationship with body lipids of patients. Demographic and clinical characteristics of patients were collected and lipid profile indices including total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and high density lipoprotein (HDL) were assayed. Restriction fragment length polymorphism-PCR (RFLP-PCR) was employed to genotype the ABCC8-C49620T polymorphism using PstI restriction enzyme. This study revealed significantly (p 0.05) of T2D for the unadjusted codominant, dominant and recessive models. Following age adjustment, the mutant genotypes (CT and TT) showed significant (p<0.05) risk of T2D for all the models with the recessive model presenting the greatest risk of T2D (OR: 2.39, 95% CI: 1.16-4.91, p<0.018). The TT genotype significantly (p<0.05) associated with high level of HDL and reduced levels of TC, TG and LDL in non-diabetic patients but was not associated with any of the demographic and clinical characteristics among T2D patients. ABCC8 C49620T polymorphism showed possible association with T2D marked by predominance of the mutant TT genotype in T2D patients. However, the relationship between TT genotype and lipid abnormalities for possible beneficial effect on people suffering from T2D is unclear

What Has Changed During the COVID-19 Pandemic? - The Effect on an Academic Breast Department in Portugal

Introduction: One year ago, Portugal entered its first lockdown because of the coronavirus disease-2019 (COVID-19) pandemic. The impact of this on delays in cancer diagnosis and treatment is a major concern, which may negatively affect the outcomes of these patients. Materials and methods: This retrospective, single-center analysis compared the clinical and pathological characteristics of breast cancer (BC) patients referred to a medical oncology first appointment between March 2020 and 2021, with the same period in the previous year. Results: Strikingly, there was a 40% reduction in the number of BC patients during lockdown. However, there was a statistically significant increase in the proportion of metastatic BC patients admitted for the first time for systemic therapy (13.6% vs. 28.9%, p = 0.003). Additionally, a statistically significant increase in the number of patients with bilateral early BC at diagnosis after March 2020 was found (7.2% vs. 1.9%, p = 0.043). Conclusion: These findings support international recommendations for an accelerated restoration of BC screening, to reduce incidence of advanced breast cancer at diagnosis and mitigate the expected impact of the COVID-19 pandemic on patients with cancer. Further work is needed to examine in detail the impact of measures to manage the COVID-19 pandemic on breast cancer outcomes.info:eu-repo/semantics/publishedVersio

Sickle cell disease in children: chronic complications and search of predictive factors for adverse outcomes

BACKGROUND: Sickle cell disease (SCD) has extremely variable phenotypes, and several factors have been associated with the severity of the disease. OBJECTIVES: To analyze the chronic complications of SCD and look for predictive risk factors for increased severity and number of complications. METHODS: Retrospective study including all children followed for SCD in the Paediatric Haematology Unit of a tertiary hospital in Portugal, who completed 17 yr old between the years 2004 and 2013. RESULTS: We identified 44 patients, 55% female and 98% black. Chronic complications occurred in 80% of cases. Slight dilatation of the left ventricle was the most frequent complication (47.7%), followed by respiratory function disturbs (43.2%), microlithiasis or cholelithiasis (40.9%), increased flow velocity of cerebral arteries (31.8%), enuresis, delayed puberty and bone abnormalities (6.8% each), sickle cell retinopathy and leg ulcer (4.6% each) and recurrent priapism (2.3%). We identified a statistically significant association between leukocytes >15 000/μL and a higher number of hospitalizations (P < 0.001) and chronic complications of the disease (P = 0.035). The occurrence of dactylitis in first year of life was also significantly associated with a higher number of hospitalizations (P = 0.004) and chronic complications (P = 0.018). The presence of α-thalassemia was associated with a lower number of chronic complications (P = 0.036). CONCLUSIONS: Leucocytosis and dactylitis in the first year of life can be predictors of SCD severity, while the presence of α-thalassemia can be protective. The determination of early predictors of chronic complications of SCD may improve the comprehensive care of these patients