The impact of late diagnosis on the survival of patients following their first AIDS-related hospitalization in Belo Horizonte, Brazil

The purpose of this study is to estimate the survival probability of patients following their first admission for the treatment of AIDS to an infectious disease reference hospital in Belo Horizonte, Brazil, during 2005. Study subjects were monitored during a 12-month period to identify factors associated with survival probability. Late diagnosis was recorded among many of the 250 study subjects: almost half (44.8%) were diagnosed less than 30 days prior to or during their hospitalization. A high mortality rate was also detected: 39.6% of the subjects died during the 12 months of monitoring. The cumulative survival probability of the cohort group was estimated at 68.0% after 3 months and at 61.2% after 12 months. However, certain patient subgroups analyzed had even lower cumulative survival probabilities after 12 months of monitoring: if diagnosed during hospitalization, it was estimated at only 48.0% and those with no record of antiretroviral treatment had a 48.5% cumulative survival probability. Patients with severe anemia had the lowest survival probability, similar among the two lymphocyte count groups (<1000 mm(3) and >= 1000 mm(3)), the former with a 45.5% survival probability and the latter with a 46.7% one. The proportional death risk was 2.5-fold higher for men residing in other area than the capital city of the State of Minas Gerais and greater metropolitan region when compared with women residing there. The findings of this study highlight the importance of early diagnosis for predicting patient survival and reinforce the necessity off acilitating HIV diagnosis.

Anemia and dementia among the elderly: the Sao Paulo Ageing & Health Study

Background: Anemia and dementia are common diseases among the elderly, but conflicting data are available regarding an association between these two conditions. We analyzed data from the Sao Paulo Ageing & Health Study to address the relationship between anemia and dementia. Methods: This cross-sectional observational study included participants aged 65 years and older from a deprived area of the borough of Butantan, Sao Paulo, Brazil. Data about demographics, education, income, and cognitive and daily life function were collected, as well as blood samples. Anemia and dementia were defined according to WHO and DSM-IV criteria, respectively. Results: Of the 2267 subjects meeting the inclusion criteria, 2072 agreed to participate in the study; of whom 1948 had a valid total blood count and were included in the analysis. Anemia was diagnosed in 203 (10.2%) participants and dementia in 99 (5.1%). The frequency of anemia was higher in patients with dementia according to univariate analysis (odds ratio (OR) = 2.00, 95% confidence interval (CI) = 1.17-3.41, p = 0.01), but this association was not present after adjusting for age (OR = 1.33, 95% CI = 0.76-2.33, p = 0.32). Further multivariate adjustment did not change the results. Conclusion: Although anemia and dementia are frequent disorders in older people, we found their relationship to be mediated exclusively by aging in this low-income population from Sao Paulo.

Defibrotide Interferes With Several Steps of the Coagulation-Inflammation Cycle and Exhibits Therapeutic Potential to Treat Severe Malaria

Objective-The coagulation-inflammation cycle has been implicated as a critical component in malaria pathogenesis. Defibrotide (DF), a mixture of DNA aptamers, displays anticoagulant, anti-inflammatory, and endothelial cell (EC)-protective activities and has been successfully used to treat comatose children with veno-occlusive disease. DF was investigated here as a drug to treat cerebral malaria. Methods and Results-DF blocks tissue factor expression by ECs incubated with parasitized red blood cells and attenuates prothrombinase activity, platelet aggregation, and complement activation. In contrast, it does not affect nitric oxide bioavailability. We also demonstrated that Plasmodium falciparum glycosylphosphatidylinositol (Pf-GPI) induces tissue factor expression in ECs and cytokine production by dendritic cells. Notably, dendritic cells, known to modulate coagulation and inflammation systemically, were identified as a novel target for DF. Accordingly, DF inhibits Toll-like receptor ligand-dependent dendritic cells activation by a mechanism that is blocked by adenosine receptor antagonist (8-p-sulfophenyltheophylline) but not reproduced by synthetic poly-A, -C, -T, and -G. These results imply that aptameric sequences and adenosine receptor mediate dendritic cells responses to the drug. DF also prevents rosetting formation, red blood cells invasion by P. falciparum and abolishes oocysts development in Anopheles gambiae. In a murine model of cerebral malaria, DF affected parasitemia, decreased IFN-gamma levels, and ameliorated clinical score (day 5) with a trend for increased survival. Conclusion-Therapeutic use of DF in malaria is proposed. (Arterioscler Thromb Vasc Biol. 2012; 32:786-798.)

Necklace fibers as histopathological marker in a patient with severe form of X-linked myotubular myopathy

X-linked myotubular myopathy due to mutations in the MTM1 gene is classically characterized by a severe neonatal phenotype and a typical muscle biopsy presenting globular and centrally located nuclei in muscle myofibers. Recently, four patients with mild late-onset form have been described, a male with a hemizygous mutation and three females with heterozygous mutations in the MTM1 gene. The muscle biopsies were performed at 13-35 years of age and a new histological marker, the necklace fibers, was described. Here, we report two siblings with the pathogenic c.664 C > T mutation in the MTM1 gene, presenting a severe muscle weakness and respiratory impairment requiring ventilatory support since the first months of life until death, at the age of 36 months and 5 months. In the older brother the muscle biopsy, performed at the age of 30 months, showed almost 100% of necklace fibers, which were not present in the younger one submitted to muscle biopsy at 5 months of age. Our findings confirm the necklace fibers can be a histopathological finding of MTM1 myopathies, even in the severe neonatal form, and suggest that the necklace fibers appear or increase in number over time. (C) 2012 Elsevier B.V. All rights reserved.

Voriconazole, Combined with Amphotericin B, in the Treatment for Pulmonary Cryptococcosis Caused by C. neoformans (Serotype A) in Mice with Severe Combined Immunodeficiency (SCID)

Cryptococcosis is a subacute or chronic systemic mycosis with a cosmopolitan nature, caused by yeast of the genus Cryptococcus neoformans. The model of systemic cryptococcosis in mice with severe combined immunodeficiency (SCID) is useful for immunological and therapeutic study of the disease in immunodeficient hosts. Amphotericin B, fluconazole and flucytosine are the drugs most commonly used to treat cryptococcosis. Voriconazole is a triazole with high bioavailability, large distribution volume, and excellent penetration of the central nervous system. The objective of this study was to evaluate treatment with amphotericin B (AMB), voriconazole (VRC), and AMB, used in combination with VRC, of experimental pulmonary cryptococcosis in a murine model (SCID). The animals were inoculated intravenously (iv) with a solution containing 3.0 x 10(5) viable cells of C. neoformans ATCC 90112, (serotype A). Treatments were performed with amphotericin B (1.5 mg/kg/day), voriconazole (40.0 mg/kg/day) and AMB (1.5 mg/kg/day) combined with VRC (40.0 mg/kg/day); began 1 day after the initial infection; were daily; and lasted 15 days. Evaluations were performed using analysis of the survival curve and isolation of yeast in the lung tissue. There was a significant increase in survival in groups treated with AMB combined with VRC, compared with the untreated group and groups receiving other treatments (P < 0.05). In the group treated only with VRC and AMB combined with VRC, there was a significant reduction (P < 0.05) in the isolation of C. neoformans in lung tissue. Amphotericin B combined with voriconazole may be an effective alternative to increasing survival and may reduce yeast in the lung tissue of mice with pulmonary cryptococcosis and SCID.

Extracorporeal membrane oxygenation in severe hypoxemia: time for reappraisal?

in 2009, during the influenza A (H1N1) epidemic, there were many reported cases of pulmonary infection with severe hypoxemia that was refractory to the ventilatory strategies and rescue therapies commonly used to treat patients with severe acute respiratory distress syndrome. Many of those cases were treated with extracorporeal membrane oxygenation (ECMO), which renewed international interest in the technique. The Extracorporeal Support Study Group was created in order to practice ECMO and to employ it in the treatment of patients with severe hypoxemia. In this article, we discuss the indications for using ECMO and report the case of a patient with refractory hypoxemia who was successfully treated with ECMO.

Upgrading of Transmission Lines in Areas of Severe Environmental Constraints

The need for increasing the loading capacity of transmission lines in a traditional way, by replacing or reinforcement of the structures and foundations on routes crossing areas considered of permanent environmental preservation, may require additional works that alter the environment. The present rigorous environmental legislation turns these changes and substitution unfeasible. One way to increase the capacity of these lines is the use of new conductor technology. The aim of this paper is to discuss the needs for upgrading a transmission line and minimize or eliminate the damage to the environment by using special conductors. Because the aluminum conductor composite reinforced technology is relatively new and considering the lack of information related to its effective performance in practical system, there is a need to verify the behavior of these conductors through monitoring procedures.

Invasive aspergillosis: a severe infection in juvenile systemic lupus erythematosus patients

Infections are an important cause of morbidity and mortality in juvenile systemic lupus erythematosus (JSLE). Among them, invasive aspergillosis (IA), which is usually related to immunosuppressed patients, has been rarely reported in JSLE. From 1983 to 2011, 5604 patients were followed at our institution and 283 (5%) met the American College of Rheumatology (ACR) classification criteria for SLE. Six (2.1%) of our JSLE patients had IA. One of them was previously reported and five will be described herein. Four of them were female. The median age at JSLE diagnosis was 12 years (8-16) and the median interval between diagnosis of JSLE and IA was 6 months (1-38). All had pulmonary involvement and three of them had systemic involvement. The median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) was 19 (7-22). Diagnosis of IA was performed by isolation of Aspergillus spp., two in bronchoalveolar lavage culture and by way of autopsy in the others. All of them were treated with corticosteroids and/or immunosuppressive drugs at IA diagnosis (azathioprine and/or intravenous cyclophosphamide). They all required treatment in the pediatric intensive care unit with mechanical ventilation and antifungal therapy (fluconazole, amphotericin B, itraconazole and/or voriconazole); nonetheless, none of them survived. In conclusion, this was the first report that evaluated the prevalence of IA in a large population of JSLE patients from a tertiary pediatric hospital, and clearly showed the severity of the outcome, especially in patients with active disease and treated with immunosuppressive agents. This study reinforces the importance of early diagnosis and treatment with certain antifungals, especially in critically ill patients. Lupus (2012) 21, 1011-1016.

Anemia prevalence and its determinants in Brazilian institutionalized elderly

Objective: To estimate the prevalence of anemia and analyze the factors associated with anemia in elderly residents of long-term care institutions. Methods: This cross-sectional study was performed in male and female elderly volunteers selected in a two-stage random sampling from long-term care institutions in the city of Maringa, Brazil (2008). A diagnosis of anemia was based on the plasma hemoglobin concentration. The independent variables analyzed were gender, age, time of residence at an institution, body mass index, and serum iron and albumin concentrations. The association between anemia and the variables was assessed using the Poisson regression with robust variance in unadjusted and adjusted analyses, considering a complex sample and a significance level of 5%. Results: The sample included 124 adults older than 60 y residing in long-term care institutions (53.0% female). The prevalence of anemia was 29% and was not significantly associated with gender, serum iron concentration, time of residence at an institution, or body mass index. Conversely, hypoalbuminemia was considered a risk factor for anemia. Conclusion: There is a high prevalence of anemia in the institutionalized elderly and hypoalbuminemia is a factor associated with this outcome. Interventions are necessary to promote improvements in the health and welfare of this population. (C) 2012 Published by Elsevier Inc.

Are the severe injuries of cutaneous leishmaniasis caused by an exacerbated Th1 response?

American tegumentary leishmaniasis (ATL) is a disease whose clinical features are strongly related to the type of immune response it induces. Herein we report an atypical presentation of cutaneous leishmaniasis in a woman with a severe and extensive sore located in her leg, and we describe the differences between the usual local immune response in ATL and the local immune response in this patient. We observed an intense inflammatory response characterized by Th1 cells and cytokines with conspicuous expression of Toll-like receptor 3 (TLR-3). Few parasites were present, but there was an extensive tissue damage. We also discuss the immunological factors that could be related to the atypical presentation.

Correction of Severe Ptosis with a Silicone Implant Suspensor: 22 Years of Experience

Background: Patients with severe ptosis caused by poor or absent function of the levator muscle but with good frontalis muscle excursion usually benefit from a frontalis sling procedure. This is currently carried out using organic or inorganic material to connect the upper eyelid to the frontalis muscle. Methods: The aim of this study was to evaluate retrospectively 112 patients who underwent frontalis sling procedures between 1989 and 2011 using a preformed silicone implant suspensor to correct severe ptosis. Results: The results obtained using this technique were good or fair in 95.54 percent of the cases and poor in 4.46 percent of the cases. The authors discuss the results of the study and the cases in which the procedure should be indicated and highlight the advantages of the method. Conclusion: The availability of this low-cost sterile device, together with the fact that it is ready to use, requires less invasive surgery, saves time, and is sufficiently versatile to allow adjustments to be made at any time, makes the silicone eyelid sling an attractive choice for correcting ptosis. (Plast. Reconstr. Surg. 129: 453e, 2012.)

Underlying Factors Associated with Anemia in Amazonian Children: A Population-Based, Cross-Sectional Study

Background: Although iron deficiency is considered to be the main cause of anemia in children worldwide, other contributors to childhood anemia remain little studied in developing countries. We estimated the relative contributions of different factors to anemia in a population-based, cross-sectional survey. Methodology: We obtained venous blood samples from 1111 children aged 6 months to 10 years living in the frontier town of Acrelandia, northwest Brazil, to estimate the prevalence of anemia and iron deficiency by measuring hemoglobin, erythrocyte indices, ferritin, soluble transferrin receptor, and C-reactive protein concentrations. Children were simultaneously screened for vitamin A, vitamin B-12, and folate deficiencies; intestinal parasite infections; glucose-6-phosphate dehydrogenase deficiency; and sickle cell trait carriage. Multiple Poisson regression and adjusted prevalence ratios (aPR) were used to describe associations between anemia and the independent variables. Principal Findings: The prevalence of anemia, iron deficiency, and iron-deficiency anemia were 13.6%, 45.4%, and 10.3%, respectively. Children whose families were in the highest income quartile, compared with the lowest, had a lower risk of anemia (aPR, 0.60; 95% CI, 0.37-0.98). Child age (<24 months, 2.90; 2.01-4.20) and maternal parity (>2 pregnancies, 2.01; 1.40-2.87) were positively associated with anemia. Other associated correlates were iron deficiency (2.1; 1.4-3.0), vitamin B-12 (1.4; 1.0-2.2), and folate (2.0; 1.3-3.1) deficiencies, and C-reactive protein concentrations (>5 mg/L, 1.5; 1.1-2.2). Conclusions: Addressing morbidities and multiple nutritional deficiencies in children and mothers and improving the purchasing power of poorer families are potentially important interventions to reduce the burden of anemia.

Clinical characteristics and possible phenotypes of an adult severe asthma population

Background: Currently, there are no studies of well-characterized severe asthmatics in Brazil. We aimed to study a population of severe treated asthmatics still uncontrolled to characterize them and define possible phenotypes. Methods: Descriptive cross-sectional outpatient study of severe asthmatics, evaluating functional and inflammatory markers, health-related quality of life, anxiety and depression symptoms, clinical control status, and characteristics related to atopy, age of asthma onset, induced sputum eosinophil levels, and airflow limitation. We also grouped the subgroups characteristics to identify phenotypes. The study is registered on ClinicalTrial.gov NCT 01089322. Results: From 128 eligible patients with severe/uncontrolled asthma, 74 fulfilled the inclusion criteria. The cohort was comprised of 85% women, frequently with a body mass index higher than 31 kg m(-2), atopy (60%), early-onset disease (50%), sputum eosinophilia (80%), comorbidities, and reduced quality of life. Nonatopics had significant higher asthma onset (19 y.a.) and twice level of induced sputum eosinophil. Late-onset patients had significantly less atopy (57%) and higher levels of induced sputum eosinophils. Non-eosinophilics had lower levels of inflammatory markers. Patients with airflow limitation had more intensive care unit admissions (56%) and 1.5 times more airway resistance. Subgroups characteristics identified a priori four well-characterized phenotypes, with 55% presenting sputum eosinophilia. Conclusion: Our data emphasize the high burden of disease, the persistence of inflammation and the existence of clinical possible phenotypes population sharing common features with published cohorts. Despite the necessity of further investigation into pathogenic mechanisms, this study with clinically difficult patient group may help to improve future asthma care. (C) 2011 Elsevier Ltd. All rights reserved.

Haemodynamic effects of aliskiren in decompensated severe heart failure

Aim: The renin-angiotensin-aldosterone system (RAAS) has dual pathways to angiotensin II production; therefore, multiple blockages may be useful in heart failure. In this study, we evaluated the short-term haemodynamic effects of aliskiren, a direct renin inhibitor, in patients with decompensated severe heart failure who were also taking angiotensin-converting enzyme ( ACE) inhibitors. Materials and methods: A total of 16 patients (14 men, two women, mean age: 60.3 years) were enrolled in the study. The inclusion criteria included hospitalisation due to decompensated heart failure, ACE inhibitor use, and an ejection fraction < 40% (mean: 21.9 +/- 6.7%). The exclusion criteria were: creatinine > 2.0 mg/dl, cardiac pacemaker, serum K+ > 5.5 mEq/l, and systolic blood pressure < 70 mmHg. Patients either received 150 mg/d aliskiren for 7 days (aliskiren group, n = 10) or did not receive aliskiren (control group, n = 6). Primary end points were systemic vascular resistance and cardiac index values. Repeated-measures analysis of variance (ANOVA) was used to assess variables before and after intervention. A two-sided p-value < 0.05 was considered statistically significant. Results: Compared to pre-intervention levels, systemic vascular resistance was reduced by 20.4% in aliskiren patients, but it increased by 2.9% in control patients (p = 0.038). The cardiac index was not significantly increased by 19.0% in aliskiren patients, but decreased by 8.4% in control patients (p = 0.127). No differences in the pulmonary capillary or systolic blood pressure values were observed between the groups. Conclusion: Aliskiren use reduced systemic vascular resistance in patients with decompensated heart failure taking ACE inhibitors.

Guanylate cyclase inhibition by methylene blue as an option in the treatment of vasoplegia after a severe burn. A medical hypothesis

Today it is known that severe burns can be accompanied by the phenomenon of vasoplegic syndrome (VS), which is manifested by persistent and diffuse vasodilation, hypotension and low vascular resistance, resulting in circulatory and respiratory failure. The decrease in systemic vascular resistance observed in VS is associated with excessive production of nitric oxide (NO). In the last 2 decades, studies have reported promising results from the administration of an NO competitor, methylene blue (MB), which is an inhibitor of the soluble guanylate cyclase (sGC), in the treatment of refractory cases of vasoplegia. This medical hypothesis rationale is focused on the tripod of burns/vasoplegia catecholamine resistant/methylene blue. This article has 3 main objectives: 1) to study the guanylate cyclase inhibition by MB in burns; 2) to suggest MB as a viable, safe and useful co-adjuvant therapeutic tool of fluid resuscitation, and; 3) to suggest MB as burns hypotensive vasoplegia amine-resistant treatment.