Inferior Vena Cava Filter Placement During Pregnancy: an Adjuvant Option When Medical Therapy Fails

The authors present a case of a 27-year-old multiparous woman, with multiple thrombophilia, whose pregnancy was complicated with deep venous thrombosis requiring placement of a vena cava filter. At 15th week of gestation, following an acute deep venous thrombosis of the right inferior limb, anticoagulant therapy with low-molecular-weight heparin (LMWH) was instituted without improvement in her clinical status. Subsequently, at 18 weeks of pregnancy, LMWH was switched to warfarin. At 30th week of gestation, the maintenance of high thrombotic risk was the premise for placement of an inferior vena cava filter for prophylaxis of pulmonary embolism during childbirth and postpartum. There were no complications and a vaginal delivery was accomplished at 37 weeks of gestation. Venal placement of inferior vena cava filters is an attractive option as prophylaxis for pulmonary embolism during pregnancy.

Zinc Therapy of Neurological Wilson's Disease in a Woman with Two Foetus with Agenesis of the Corpus Callosum

8A>C>86A G:EDGI: A patient diagnosed Wilson’s disease (WD) 22 years previously, successfully treated initially with zinc, developed neuropsychiatric disease after years of irregular therapy. Reassuming zinc therapy was successful. After a normal pregnancy, she had two therapeutic abortions for corpus callosum agenesis, and a missed abortion. We review the genetics, physiopathology, clinics and imagiologic response to zinc therapy, the problems of pregnancy in WD, advising to maintain therapy. A hypothetic cause for fetus brain anomaly would be hypocupremia due to zinc therapy, confronting with two other possibilities, one related to Wilson’s disease in itself, other due to a congenital syndrome of agenesis of the corpus callosum, impossible to diagnose by our available diagnostic methods.

Host-induced changes in the cell surface N-linked glycoproteins, from Aspergillus fumigatus. Search for specific targets with potential for clinical therapy and/or diagnosis.

This dissertation is presented to obtain a Master degree in Structural and Functional Biochemistry

Long-Term Evaluation of Recurrence after Photodynamic Therapy with Topical Methyl Aminolevulinate for Non-Melanoma Skin Cancer: a Hospital-Based Study

Introduction & Objectives: Several factors may influence the decision to pursue nonsurgical modalities for the treatment of non-melanoma skin cancer. Topical photodynamic therapy (PDT) is a non-invasive alternative treatment reported to have a high efficacy when using standardized protocols in Bowen’s disease (BD), superficial basal cell carcinoma (BCC) and in thin nodular BCC. However, long-term recurrence studies are lacking. The aim of this study was to evaluate the long-term efficacy of PDT with topical methylaminolevulinate (MAL) for the treatment of BD and BCC in a dermato-oncology department. Materials & Methods: All patients with the diagnosis of BD or BCC, treated with MAL-PDT from the years 2004 to 2008, were enrolled. Treatment protocol included two MAL-PDT sessions one week apart repeated at three months when incomplete response, using a red light dose of 37-40 J/cm2 and an exposure time of 8’20’’. Clinical records were retrospectively reviewed, and data regarding age, sex, tumour location, size, treatment outcomes and recurrence were registered. Descriptive analysis was performed using chi square tests, followed by survival analysis with the Kaplan-Meier and Cox regression models. Results: Sixty-eight patients (median age 71.0 years, P25;P75=30;92) with a total of 78 tumours (31 BD, 45 superficial BCC, 2 nodular BCC) and a median tumour size of 5 cm2 were treated. Overall, the median follow-up period was 43.5 months (P25;P75=0;100), and a total recurrence rate of 33.8% was observed (24.4 % for BCC vs. 45.2% for BD). Estimated recurrence rates for BCC and BD were 5.0% vs. 7.4% at 6 months, 23.4% vs. 27.9% at 12 months, and 30.0% vs. 72.4% at 60 months. Both age and diagnosis were independent prognostic factors for recurrence, with significantly higher estimated recurrence rates in patients with BD (p=0.0036) or younger than 58 years old (p=0.039). The risk of recurrence (hazard ratio) was 2.4 times higher in patients with BD compared to superficial BCC (95% CI:1.1-5.3; p=0.033), and 2.8 times higher in patients younger than 58 years old (95% CI:1.2-6.5; p=0.02). Conclusions: In the studied population, estimated recurrence rates are higher than those expected from available literature, possibly due to a longer follow-up period. To the authors’ knowledge there is only one other study with a similar follow-up period, regarding BCC solely. BD, as an in situ squamous cell carcinoma, has a higher tendency to recur than superficial BCC. Despite greater cosmesis, PDT might no be the best treatment option for young patients considering their higher risk of recurrence.

Vulvar Lichen Sclerosus: Efficacy of Photodynamic Therapy Under Conscious Sedation with Inhaled 50% Nitrous Oxide and Oxygen Mixture

Anogenital lichen sclerosus is a chronic, inflammatory, mucocutaneous disorder of significant morbidity. Common symptoms include pruritus, pain, dysuria, and dyspareunia, frequently of difficult control. Photodynamic therapy (PDT) may be an effective therapeutic option in selected cases refractory to first--‐line treatment options. However, procedure--‐related pain is a limiting factor in patient adherence to treatment. Conscious sedation and analgesia with a ready--‐to--‐use gas mixture of nitrous oxide and oxygen is useful in short--‐term procedures. It provides a rapid, effective, and short--‐lived effect, without the need for anesthesiology support. A 75--‐year--‐old woman presented with a highly symptomatic, histologically confirmed vulvar lichen sclerosus, with at least 15 years of evolution. Pain, pruritus, and dysuria were intense and disabling. Treatment with ultrapotent topical corticosteroids proved to be ineffective despite patient compliance. She was then referred for PDT. A total of 3 sessions were performed, held at a mean interval of 9 weeks, and under the analgesic and sedative effect of nitrous oxide/oxygen gas. Response to treatment was evaluated through a daily, self--‐reported pain rating scale. Dysuria remitted completely after the first PDT session. An 80% reduction in pruritus and pain was observed after the third session, and has been sustained for the past six months without further need for topical corticotherapy. Treatment sessions were well tolerated and pain-- free, with no side effects to report. PDT appears to be effective in the symptomatic treatment of vulvar lichen sclerosus. To the authors’ knowledge this is the first case reporting the use of inhaled nitrous oxide/oxygen gas mixture during PDT performed in the genital area. Its analgesic and sedative effects may increase patients’ adherence to this painful procedure. Furthermore, given its safety, it can be easily managed in outpatient clinics by trained dermatologists.

RISK FACTORS OF HIV-1 VERTICAL TRANSMISSION (VT) AND THE INFLUENCE OF ANTIRETROVIRAL THERAPY (ART) IN PREGNANCY OUTCOME

In the absence of intervention, the rate of vertical transmission of HIV can range from 15-45%. With the inclusion of antiretroviral drugs during pregnancy and the choice of delivery route this amounts to less than 2%. However ARV use during pregnancy has generated several questions regarding the adverse effects of the gestational and neonatal outcome. This study aims to analyze the risk factors for vertical transmission of HIV-1 seropositive pregnant women living in Rio Grande and the influence of the use of ARVs in pregnancy outcome. Among the 262 pregnant women studied the rate of vertical transmission of HIV was found to be 3.8%. Regarding the VT, there was a lower risk of transmission when antiretroviral drugs were used and prenatal care was conducted at the referral service. However, the use of ART did not influence the outcome of pregnancy. However, initiation of prenatal care after the first trimester had an influence on low birth weight, as well as performance of less than six visits increased the risk of prematurity. Therefore, the risk factors analyzed in this study appear to be related to the realization of inadequate pre-natal and maternal behavior.

Renal Replacement Therapy in Critically Ill Patients - What Modality Should We Choose?

A lesão renal aguda é uma complicação comum nas unidades de cuidados intensivos. A mortalidade do doente crítico que requer diálise é extremamente elevada, apesar dos avanços significativos dos cuidados prestados a estes doentes. Há várias décadas que se discute o tipo de modalidade dialítica a oferecer a estes doentes (continua ou intermitente) e os principais fatores que pesam na decisão clínica são os meios e a experiência do centro, bem como a condição clínica do doente. Vários estudos tentaram estabelecer a melhor abordagem ao doente crítico com lesão renal aguda e necessidade dialítica, em termos de sobrevida do doente e recuperação renal. Nesta revisão tentarei resumir as evidências disponíveis sobre este tema.

DISCORDANCE BETWEEN BODY MASS INDEX AND ANTHROPOMETRIC MEASUREMENTS AMONG HIV-1-INFECTED PATIENTS ON ANTIRETROVIRAL THERAPY AND WITH LIPOATROPHY/LIPOHYPERTROPHY SYNDROME

Introduction: Highly Active Antiretroviral Therapy (HAART) has improved and extended the lives of thousands of people living with HIV/AIDS around the world. However, this treatment can lead to the development of adverse reactions such as lipoatrophy/lipohypertrophy syndrome (LLS) and its associated risks. Objective: This study was designed to assess the prevalence of self-reported lipodystrophy and nutritional status by anthropometric measurements in patients with HIV/AIDS. Methods: An observational study of 227 adult patients in the Secondary Immunodeficiencies Outpatient Department of Dermatology, Hospital das Clínicas, Faculty of Medicine, University of São Paulo (3002 ADEE-HCFMUSP). The sample was divided into three groups; Group 1 = 92 patients on HAART and with self-reported lipodystrophy, Group 2 = 70 patients on HAART without self-reported lipodystrophy and Group 3 = 65 patients not taking HAART. The nutritional status of individuals in the study sample was determined by body mass index (BMI) and percentage of body fat (% BF). The cardiovascular risk and diseases associated with abdominal obesity were determined by waist/hip ratio (WHR) and waist circumference (WC). Results: The prevalence of self-reported lipoatrophy/lipohypertrophy syndrome was 33% among women and 59% among men. Anthropometry showed depletion of fat mass in the evaluation of the triceps (TSF) in the treatment groups with HAART and was statistically independent of gender; for men p = 0.001, and for women p = 0.007. Similar results were found in the measurement of skin folds of the upper and lower body (p = 0.001 and p = 0.003 respectively). In assessing the nutritional status of groups by BMI and % BF, excess weight and body fat were more prevalent among women compared to men (p = 0.726). The WHR and WC revealed risks for cardiovascular and other diseases associated with abdominal obesity for women on HAART and with self-reported LLS (p = 0.005) and (p = 0.011). Conclusions: Anthropometric measurements were useful in the confirmation of the prevalence of LLS. BMI alone does not appear to be a good parameter for assessing the nutritional status of HIV-infected patients on HAART and with LLS. Other anthropometric measurements are needed to evaluate patients with the lipoatrophy/lipohypertrophy syndrome.

EFFECT OF HIGHLY ACTIVE ANTIRETROVIRAL THERAPY ON VAGINAL Candida spp. ISOLATION IN HIV-INFECTED COMPARED TO HIV-UNINFECTED WOMEN

 Vulvovaginal candidiasis (VVC) in HIV-infected women contributed to the impairment of their quality of life. The aim of this study was to evaluate the effect of highly active antiretroviral therapy (HAART) use on the vaginal Candida spp. isolation in HIV-infected compared to HIV-uninfected women. This cross-sectional study included 178 HIV-infected (HIV group) and 200 HIV-uninfected women (control) that were studied at the Specialized Assistance Service (SAE) for sexually transmitted diseases (STD)/AIDS of the city of Maringá, Brazil, from April 1 to October 30, 2011. The yeasts were isolated and identified by phenotypic and molecular methods. The in vitro antifungal susceptibility to fluconazole, itraconazole, nystatin and amphotericin B was tested by the reference microdilution method. Higher frequencies of total vaginal Candida spp. isolation were found in the HIV-infected group than in the control group. However, both groups showed a similar frequency of colonization and VVC. Although C. albicans was the most frequent and sensitive to azolics and polyenes in both HIV-infected and uninfected women, the emerging resistance of C. glabrata to amphotericin B in the HIV-infected women was observed. Although higher frequency of vaginal Candida spp. isolation had been observed in the HIV-infected than in HIV-uninfected women, colonization and VVC showed similar frequency in both groups, indicating that HAART appears to protect against vaginal colonization and VVC.

Interictal Spike EEG Source Analysis in Hypothalamic Hamartoma Epilepsy

Objective: The epilepsy associated with the hypothalamic hamartomas constitutes a syndrome with peculiar seizures, usually refractory to medical therapy, mild cognitive delay, behavioural problems and multifocal spike activity in the scalp electroencephalogram (EEG). The cortical origin of spikes has been widely assumed but not specifically demonstrated. Methods: We present results of a source analysis of interictal spikes from 4 patients (age 2–25 years) with epilepsy and hypothalamic hamartoma, using EEG scalp recordings (32 electrodes) and realistic boundary element models constructed from volumetric magnetic resonance imaging (MRIs). Multifocal spike activity was the most common finding, distributed mainly over the frontal and temporal lobes. A spike classification based on scalp topography was done and averaging within each class performed to improve the signal to noise ratio. Single moving dipole models were used, as well as the Rap-MUSIC algorithm. Results: All spikes with good signal to noise ratio were best explained by initial deep sources in the neighbourhood of the hamartoma, with late sources located in the cortex. Not a single patient could have his spike activity explained by a combination of cortical sources. Conclusions: Overall, the results demonstrate a consistent origin of spike activity in the subcortical region in the neighbourhood of the hamartoma, with late spread to cortical areas.

The role of Rac1-modulated gene transcription in tumorigenesis

Dissertation presented to obtain the Ph.D degree in Biology

PARACOCCIDIOIDOMYCOSIS: CHALLENGES IN THE DEVELOPMENT OF A VACCINE AGAINST AN ENDEMIC MYCOSIS IN THE AMERICAS

SUMMARYParacoccidioidomycosis (PCM), caused by Paracoccidioides spp, is an important endemic mycosis in Latin America. There are two recognized Paracoccidioides species, P. brasiliensis and P. lutzii, based on phylogenetic differences; however, the pathogenesis and disease manifestations of both are indistinguishable at present. Approximately 1,853 (~51,2%) of 3,583 confirmed deaths in Brazil due to systemic mycoses from 1996-2006 were caused by PCM. Antifungal treatment is required for patients with PCM. The initial treatment lasts from two to six months and sulfa derivatives, amphotericin B, azoles and terbinafine are used in clinical practice; however, despite prolonged therapy, relapses are still a problem. An effective Th1-biased cellular immune response is essential to control the disease, which can be induced by exogenous antigens or modulated by prophylactic or therapeutic vaccines. Stimulation of B cells or passive transference of monoclonal antibodies are also important means that may be used to improve the efficacy of paracoccidioidomycosis treatment in the future. This review critically details major challenges facing the development of a vaccine to combat PCM.

IMPACT OF THE PEGYLATED-INTERFERON AND RIBAVIRIN THERAPY ON THE TREATMENT-RELATED MORTALITY OF PATIENTS WITH CIRRHOSIS DUE TO HEPATITIS C VIRUS

Although the protease inhibitors have revolutionized the therapy of chronic hepatitis C (CHC), the concomitant use of pegylated-interferon (PEG-IFN) and ribavirin (RBV) is associated to a high rate of adverse effects. In this study, we evaluated the consequences of PEG-IFN and RBV and their relationship with mortality in patients with cirrhosis. METHODS: Medical records of CHC who underwent treatment with PEG-IFN and RBV in a public hospital in Brazil were evaluated. All the patients with cirrhosis were selected, and their clinical and laboratory characteristics, response to treatment, side effects and mortality were evaluated. RESULTS: From the 1,059 patients with CHC, 257 cirrhotic patients were evaluated. Of these, 45 (17.5%) achieved sustained viral response (SVR). Early discontinuation of therapy occurred in 105 (40.8%) patients, of which 39 (15.2%) were due to serious adverse effects. The mortality rate among the 257 cirrhotic patients was 4.3%, occurring in 06/242 (2.4%) of the Child-A, and in 05/15 (33.3%) of the Child-B patients. In conclusion, the treatment of patients with cirrhosis due to HCV with PEG-IFN and RBV shows a low SVR rate and a high mortality, especially in patients with liver dysfunction.

BRAIN ABSCESS DUE TO Staphylococcus aureus OF CRYPTOGENIC SOURCE IN AN HIV-1 INFECTED PATIENT IN USE OF ANTIRETROVIRAL THERAPY

The spectrum of neurological complications associated with human immunodeficiency virus type 1 (HIV-1) infection is broad. The most frequent etiologies include primary diseases (caused by HIV itself) or secondary diseases (opportunistic infections or neoplasms). Despite these conditions, HIV-infected patients are susceptible to other infections observed in patients without HIV infection. Here we report a rare case of a brain abscess caused by Staphylococcus aureus in an HIV-infected patient. After drainage of the abscess and treatment with oxacilin, the patient had a favorable outcome. This case reinforces the importance of a timely neurosurgical procedure that supported adequate management of an unusual cause of expansive brain lesions in HIV-1 infected patients.