Clinical laboratory assessment of hepatitis C and HIV coinfected patients according to the antiretroviral therapy received

During the year of 2001, a retrospective, descriptive study in order to determine the influence of the antiretroviral therapy received by 111 HIV-HCV coinfected patients who had undergone at least one liver biopsy was conduced, 74 of them were treated with a protease inhibitor regimen (WPI), and 37 with a non-protease inhibitor regimen (NPI). The main characteristics found were: a young patient population (mean age 41 years old in both groups), composed in most part of male individuals (74.3% WPI and 51.4% NPI) with previous risk factors for both infections (WPI 93.2% and NPI 89.2%). The most significant findings included AIDS-defining disease (WPI 18.9% and NPI 13.5% of the cases), elevated hepatic enzyme levels (WPI: SGOT 52.1 and NPI 53.2), absence of liver disease-related symptoms (16.2% for both groups), average CD4 count > 350 for both groups (WPI 362.2 and NPI 378.1), predominantly low-grade fibrosis in both populations (0-2 in 63.6% of WPI patients and in 80% of NPI patients), with necro-inflammatory activity ranging from 5-7 in 51.3% and 42.9% of WPI patients and NPI patients, respectively. It is suggested a sequential biopsy to better evaluate the evolution of the hepatic disease, according to the HAART regimen received.

Treatment of chronic hepatitis C in non-responsive patients with pegylated interferon associated with ribavirin and thalidomide: report of six cases of total remission

Hepatitis C virus (HCV) infection is an important public health issue worldwide. It is estimated that over 170 million people are infected with the virus. The present study reports six cases in which patients did not respond to combination therapy with pegylated interferon and ribavirin. However, after the addition of thalidomide to the therapy, the patients presented negative RNA PCR. The use of thalidomide combined with pegylated interferon and ribavirin for the treatment of hepatitis C is described here for the first time in the related literature.

Asymptomatic oral carriage of Candida species in HIV-infected patients in the highly active antiretroviral therapy era

Oropharyngeal candidiasis is the most common opportunistic fungal infection in individuals infected with human immunodeficiency virus. CD4+ lymphocytes count and the quantification of viral RNA in blood plasma have been found to be the main markers of HIV disease progression. The present study was conducted to evaluate Candida sp. diversity in the oral cavity of HIV-infected patients and to determine whether there was association of CD4+ cell count and viral load with asymptomatic oral Candida carriage. Out of 99 HIV-positive patients studied, 62 (62.6%) had positive culture for Candida (oral carriage) and 37 patients (37.4%) had Candida negative culture (no oral carriage). The etiologic agents most common were C. albicans and C. tropicalis. The range of CD4+ was 6-2305 cells/mm³ in colonized patients and 3-839 cells/mm³ for non-colonized patients, while the viral load was 60-90016 copies/mL for colonized patients and 75-110488 copies/mL for non colonized patients. The viral load was undetectable in 15 colonized patients and in 12 non colonized patients. Our results showed that there was no significant difference of the variables CD4+ cell count and viral load between oral candida carriage and no oral candida carriage patients.

Simultaneous quantitation of serum HBV DNA and HBeAg can distinguish between slow and fast viral responses to antiviral therapy in patients with chronic hepatitis B

BACKGROUND: The quantitation of serum HBeAg is not commonly used to monitor viral response to therapy in chronic hepatitis B. METHODS: In this study, 21 patients receiving varying therapies were followed and their viral response monitored by concomitant viral load and HBeAg quantitation in order to study the meaning and the kinetics of both parameters. RESULTS: It was possible to distinguish between three different patterns of viral response. The first was characterized by a simultaneous decrease in serum HBV DNA and HBeAg. The second pattern was characterized by a decrease in serum HBeAg but persistent detection of HBV DNA. The third pattern was characterized by undetectable HBV DNA with persistent HBeAg positivity, which points to a non-response (Pattern III-B) except when HBeAg levels showed a slow but steady drop, characterizing a "slow responder" patient (Pattern III-A). CONCLUSIONS: The first pattern is compatible with a viral response. A long-term HBeAg seropositivity with a slow and persistent decrease (Pattern III-A) is also compatible with a viral response and calls for a prolongation of anti-viral treatment.

Chronic hepatitis C: hepatic iron content does not correlate with response to antiviral therapy

The complex interaction between hepatitis C virus infection, iron homeostasis and the response to antiviral treatment remains controversial. The aim of this study was to evaluate the influence of hepatic iron concentration (HIC) on the sustained virological response (SVR) to antiviral therapy in patients with chronic hepatitis C. A total of 50 patients who underwent pretreatment liver biopsy with assessment of HIC by graphite furnace atomic absorption spectroscopy and were subsequently submitted to antiviral treatment with interferon/peginterferon and ribavirin were included in the study. Patients with alcoholism, history of multiple blood transfusion, chronic kidney disease, hemolytic anemia and parenteral iron therapy were excluded. The iron related markers and HIC were compared between those who achieved an SVR and non-responders (NR) patients. The mean age was 45.7 years and the proportion of patients' gender was not different between SVR and NR patients. The median serum iron was 138 and 134 µg/dL (p = 0.9), the median serum ferritin was 152.5 and 179.5 ng/mL (p = 0.87) and the median HIC was 9.9 and 8.2 µmol/g dry tissue (p = 0.51), for SVR and NR patients, respectively. Thus, hepatic iron concentration, determined by a reliable quantitative method, was not a negative predictive factor of SVR in patients with chronic hepatitis C presenting mild to moderate hepatic iron accumulation.

Efeitos de um Programa de Reabilitação Respiratória em Indivíduos Operados a Cancro do Pulmão

O tratamento cirúrgico e os tratamentos coadjuvantes do cancro do pulmão de não pequenas células (CPNPC), como a quimioterapia, afetam negativamente a saúde física e psicológica dos pacientes. Um programa de reabilitação respiratória (PRR) pode ajudar no controlo de sintomas, melhorar a capacidade funcional e a qualidade de vida desta população. Objetivo: verificar a influência de um programa de reabilitação respiratória composto por fisioterapia torácica, treino aeróbio, treino de força e educação para a saúde, em parâmetros como a qualidade de vida, a ansiedade e depressão, a dispneia, a capacidade funcional para realizar exercício e a força muscular, em 6 doentes operados a CPNPC. Métodos: estudo retrospetivo, do tipo série de estudos de caso, que incluiu 6 casos clínicos. As medidas de resultados utilizadas foram: qualidade de vida; dispneia; ansiedade e depressão; capacidade funcional para a marcha; e força muscular. Resultados: no final do PRR, os 6 participantes apresentaram melhoria nos níveis de qualidade de vida, uma diminuição nos valores de ansiedade e depressão e um grau de dispneia inferior ao avaliado inicialmente. Foi ainda verificado um aumento da capacidade funcional para o exercício e da força muscular em todos os casos clínicos. Conclusão: O PRR pareceu produzir efeitos positivos na diminuição dos sintomas, assim como melhorou a qualidade de vida, a capacidade funcional para a marcha e a força muscular dos 6 participantes.

Acute gouty arthritis as a manifestation of immune reconstitution inflammatory syndrome after initiation of antiretroviral therapy

Immune reconstitution inflammatory syndrome (IRIS) in HIV-infected subjects initiating antiretroviral therapy most commonly involves new or worsening manifestations of previously subclinical or overt infectious diseases. Reports of non-infectious IRIS are much less common but represent important diagnostic and treatment challenges. We report on a 34-year-old HIV-infected male patient with no history of gout who developed acute gouty arthritis in a single joint one month after initiating highly active antiretroviral therapy.

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

Non-clinical isolates bring new findings on enterococcal virulence

Dissertation presented to obtain the PhD degree in Biology

Coronary Revascularization Induces a Shift From Cardiac Toward Noncardiac Mortality Without Improving Survival in Vascular Surgery Patient

OBJECTIVE: Although evidence has shown that ischemic heart disease (IHD) in vascular surgery patients has a negative impact on the prognosis after surgery, it is unclear whether directed treatment of IHD may influence cause-specific and overall mortality. The objective of this study was to determine the prognostic implication of coronary revascularization (CR) on overall and cause-specific mortality in vascular surgery patients. METHODS: Patients undergoing surgery for abdominal aortic aneurysm, carotid artery stenosis, or peripheral artery disease in a university hospital in The Netherlands between January 2003 and December 2011 were retrospectively included. Survival estimates were obtained by Kaplan-Meier and Cox regression analysis. RESULTS: A total of 1104 patients were included. Adjusted survival analyses showed that IHD significantly increased the risk of overall mortality (hazard ratio [HR], 1.50; 95% confidence interval, 1.21-1.87) and cardiovascular death (HR, 1.93; 95% confidence interval, 1.35-2.76). Compared with those without CR, patients previously undergoing CR had similar overall mortality (HR, 1.38 vs 1.62; P = .274) and cardiovascular mortality (HR, 1.83 vs 2.02; P = .656). Nonrevascularized IHD patients were more likely to die of IHD (6.9% vs 35.7%), whereas revascularized IHD patients more frequently died of cardiovascular causes unrelated to IHD (39.1% vs 64.3%; P = .018). CONCLUSIONS: This study confirms the significance of IHD for postoperative survival of vascular surgery patients. CR was associated with lower IHD-related death rates. However, it failed to provide an overall survival benefit because of an increased rate of cardiovascular mortality unrelated to IHD. Intensification of secondary prevention regimens may be required to prevent this shift toward non-IHD-related death and thereby improve life expectancy.

Cost-Effectiveness of Non-Vitamin K Antagonist Oral Anticoagulants for Atrial Fibrillation in Portugal

INTRODUCTION AND OBJECTIVES:Recently, three novel non-vitamin K antagonist oral anticoagulants received approval for reimbursement in Portugal for patients with non-valvular atrial fibrillation (AF). It is therefore important to evaluate the relative cost-effectiveness of these new oral anticoagulants in Portuguese AF patients. METHODS: A Markov model was used to analyze disease progression over a lifetime horizon. Relative efficacy data for stroke (ischemic and hemorrhagic), bleeding (intracranial, other major bleeding and clinically relevant non-major bleeding), myocardial infarction and treatment discontinuation were obtained by pairwise indirect comparisons between apixaban, dabigatran and rivaroxaban using warfarin as a common comparator. Data on resource use were obtained from the database of diagnosis-related groups and an expert panel. Model outputs included life years gained, quality-adjusted life years (QALYs), direct healthcare costs and incremental cost-effectiveness ratios (ICERs). RESULTS:Apixaban provided the most life years gained and QALYs. The ICERs of apixaban compared to warfarin and dabigatran were €5529/QALY and €9163/QALY, respectively. Apixaban was dominant over rivaroxaban (greater health gains and lower costs). The results were robust over a wide range of inputs in sensitivity analyses. Apixaban had a 70% probability of being cost-effective (at a threshold of €20 000/QALY) compared to all the other therapeutic options. CONCLUSIONS:Apixaban is a cost-effective alternative to warfarin and dabigatran and is dominant over rivaroxaban in AF patients from the perspective of the Portuguese national healthcare system. These conclusions are based on indirect comparisons, but despite this limitation, the information is useful for healthcare decision-makers.

Long-Term Recurrence of Nonmelanoma Skin Cancer after Topical Methylaminolevulinate Photodynamic Therapy in a Dermato-Oncology Department

BACKGROUND: Most available studies on the efficacy of topical photodynamic therapy focus on short-to medium-term results. Long-term data are scarce. OBJECTIVE: To evaluate the long-term efficacy of photodynamic therapy with topical methylaminolevulinate to treat Bowen's disease and basal cell carcinoma in the clinical practice setting of a dermato-oncology department. METHODS: The study included patients diagnosed with Bowen's disease or basal cell carcinoma, and who received photodynamic therapy from 2004 to 2008. Treatment protocol and clinical follow-up were standardized. The primary endpoint was clinically observed recurrence in a previous photodynamic therapy-treated area. Descriptive and survival analyses were performed. RESULTS: A total of 31 Bowen's disease lesions and 44 superficial basal cell carcinoma were treated, with a median follow-up of 43.5 months. Recurrence was observed in 14 Bowen's disease lesions (53.8%) and in 11 superficial basal cell carcinoma (33.3%). Significantly higher estimates for recurrence rates were found in patients with Bowen's disease (p=0.0036) or those aged under 58 years (p=0.039). The risk of recurrence was higher in patients with Bowen's disease than in those with superficial basal cell carcinoma and younger patients. CONCLUSIONS: Recurrence should be considered when choosing to treat non-melanoma skin cancer with photodynamic therapy. Younger age and Bowen's disease were independent predictors for long-term recurrence, suggesting the need to establish an extended period of follow-up for this subset of patients.

Rate of reversion of hepatosplenic schistosomiasis after specific therapy

Seventy patients with hepatosplenic schistosomiasis were treated with oxamniquine. The patients lived iti an endemic area and were evaluated 6, 18 and 24 months after treatment, during which time transmission in the area was interrupted. After treatment, clinical improvement occurred in 49 (70%) of the patients, as seen by reduction in visceromegaly and reversion of liver nodules. Reversion of hepatosplenic disease occurred in 28 (40%) patients and in liver nodularity in 26 (47.3%)patients after 24 months. Reversion of hepatosplenic disease was seen in 12 (21%) patients and liver nodules disappeared in 4 (8.5%) as early as 6 months after treatment. In general, hepatosplenomegaly reverses earlier than liver nodularity. Itis notable that reversion of hepatosplenic disease occurred in many individuals with a history ofprevious treatment and also in some with advanced age. In four cases this clinical form of the disease had existed for 20 years. Therefore, there must exist factors other than age and duration of the condition which determine the reversibility of this clinical form. Ourresults reinforce the concept that, in patients with hepatosplenic disease without esophageal hemorrhages, specific treatment shouldpreceed surgical intervention even in those with a history of previous treatment. At least 18 months should be allowed for the ejfects of treatment to be manifest.

Overexpressing BDNF in Neural Stem Cells using non-viral gene delivery strategies

Dissertação para obtenção do Grau de Mestre em Biotecnologia

The role of integrated home-based care in patient adherence to antiretroviral therapy

Non-adherence is one of the primary obstacles to successful antiretroviral therapy in HIV+ patients worldwide. In Brazil, the Domiciliary Therapeutic Assistance is a multidisciplinary and integrated home-based assistance program provided for HIV+ patients confined in their homes due to physical deficiency. This study investigated ADT's ability to monitor and promote appropriate adherence to ARV therapy. Fifty-six individuals were recruited from three study groups: Group 1 - patients currently in the ADT program, Group 2 - 21 patients previously treated by the ADT program, and Group 3 - 20 patients who have always been treated using conventional ambulatory care. Using multivariable self-reporting to evaluate adherence, patients in the ADT program had significantly better adherence than patients in ambulatory care (F = 6.66, p = 0.003). This effect was independent of demographic and socioeconomic characteristics as well as medical history. Patients in the ADT program also showed a trend towards greater therapeutic success than ambulatory patients. These results suggest the incorporation of characteristics of ADT in conventional ambulatory care as a strategy to increase adherence to ARV therapy.