Chronic American trypanosomiasis: parasite persistence in endomyocardial biopsies is associated with high-grade myocarditis

Myocyte diameter, fractional area of collagen, intensity of myocarditis and parasite persistence (explored by immunohistochemistry and PCR) were evaluated in serial sections of endomyocardial biopsies from 29 outpatients with chronic chagasic cardiopathy. The patients, 25 males and four females with a mean (S.D.) age of 43 (9) years, were subsequently followed up for 3-2861 days (median=369 days). During this follow-up, 16 (55%) of the patients died. The biopsies revealed myocarditis in 25 (86%) of the patients and high-grade myocarditis in 14 (56%). Although immunohistochemistry failed to demonstrate Trypanosoma cruzi antigens in any of the samples, five (33%) of the 15 biopsies successfully tested in the PCR-based assay for T. cruzi DNA were found positive, indicating parasite persistence. There was a significant positive association between myocardial parasite persistence and high-grade myocarditis (P= 0.014); five (71%,) of the seven endomyocardial biopsies with high-grade myocarditis that were successfully tested in the PCR assays showed persistent T. cruzi DNA. The survival time of the patients was not, however, found to be significantly associated with myocardial parasite persistence, any of the morphometric measurements taken, or the presence or intensity of myocarditis.

Incidence and risk factors for agranulocytosis in Latin American countries - the Latin study

Purpose LATIN is a multinational case-control study designed to identify risk factors for agranulocytosis and to estimate the incidence rate of the disease in some Latin American countries. Methods Each study site in Brazil, Argentina and Mexico conducted an active search of agranulocytosis patients in hematology clinics and looked for possible associations with drug use. Results The overall incidence rate was 0.38 cases per 1 million inhabitant-years. Agranulocytosis patients more often took medications already associated with agranulocytosis than controls (p=0.01), mainly methimazole (OR 44.2, 95% CI 6.8 to infinity). The population attributable risk percentage (etiologic fraction) was 56%. The use of nutrient supplements was more frequent among patients than controls (p=0.03). Conclusions Agranulocytosis seems to be very rare in Latin America. The lower than expected number of cases identified during the study period precluded estimation of the risk associated to individual drugs, with the exception of methimazol. However, this is the longest series of agranulocytosis cases ever gathered in Latin America, and information on drug exposures was collected prospectively. The conclusion is that drug-induced agranulocytosis does not seem to be a major public health problem in the study regions.

Time- and Fluid-Sensitive Resuscitation for Hemodynamic Support of Children in Septic Shock Barriers to the Implementation of the American College of Critical Care Medicine/Pediatric Advanced Life Support Guidelines in a Pediatric Intensive Care Unit in a Developing World

Objectives: To analyze mortality rates of children with severe sepsis and septic shock in relation to time-sensitive fluid resuscitation and treatments received and to define barriers to the implementation of the American College of Critical Care Medicine/Pediatric Advanced Life Support guidelines in a pediatric intensive care unit in a developing country. Methods: Retrospective chart review and prospective analysis of septic shock treatment in a pediatric intensive care unit of a tertiary care teaching hospital. Ninety patients with severe sepsis or septic shock admitted between July 2002 and June 2003 were included in this study. Results: Of the 90 patients, 83% had septic shock and 17% had severe sepsis; 80 patients had preexisting severe chronic diseases. Patients with septic shock who received less than a 20-mL/kg dose of resuscitation fluid in the first hour of treatment had a mortality rate of 73%, whereas patients who received more than a 40-mL/kg dose in the first hour of treatment had a mortality rate of 33% (P < 0.05.) Patients treated less than 30 minutes after diagnosis of severe sepsis and septic shock had a significantly lower mortality rate (40%) than patients treated more than 60 Minutes after diagnosis (P < 0.05). Controlling for the risk of mortality, early fluid resuscitation was associated with a 3-fold reduction in the odds of death (odds ratio, 0.33; 95% confidence interval, 0.13-0.85). The most important barriers to achieve adequate severe sepsis and septic shock treatment were lack of adequate vascular access, lack of recognition of early shock, shortage of health care providers, and nonuse of goals and treatment protocols. Conclusions: The mortality rate was higher for children older than years, for those who received less than 40 mL/kg in the first hour, and for those whose treatment was not initiated in the first 30 Minutes after the diagnosis of septic shock. The acknowledgment of existing barriers to a timely fluid administration and the establishment of objectives to overcome these barriers may lead to a more successful implementation of the American College of Critical Care Medicine guidelines and reduced mortality rates for children with septic shock in the developing world.

In vitro infectivity of species of Leishmania (Viannia) responsible for American cutaneous leishmaniasis

There is little available information regarding the infectivity of New World Leishmania species, particularly those from the Amazonian Brazil, where there are six species of the subgenus Viannia causing American cutaneous leishmaniasis (ACL). The aim of this study was to compare, in vitro, the potential infectivity of the following Leishmania (Viannia) spp.: L. (V.) braziliensis from localized cutaneous leishmaniasis (LCL) and mucocutaneous leishmaniasis (MCL) patients, L. (V.) guyanensis, L. (V.) shawi, L. (V.) lainsoni and L. (V.) naiffi from LCL patients only, in cultured BALB/c mice peritoneal macrophage, as well as the production of NO by the infected cells. The infectivity of parasites was expressed by the infection index and, the nitric oxide (NO) production in the macrophage culture supernatant was measured by the Griess method. It was found that L. (V.) braziliensis from MCL, the more severe form of disease, showed the highest (p <= 0.05) infection index (397), as well as the lowest NO production (2.15 mu M) compared with those of other species. In contrast, L. (V.) naiffi which is less pathogenic for the human showed the lowest infection index (301) and the highest NO production (4.11 mu M). These results demonstrated a negative correlation between the infectivity and the ability of these parasites to escape from the microbicidal activity of the host cell.

Factor XIIIa plus Dermal Dendrocyte Parasitism in American Tegumentary Leishmaniasis Skin Lesions

Dendritic cells belong to a family of antigen-presenting cells that are localized at the entry sites, such as skin and mucosa. Dendritic cells are related to immune surveillance function. The role of Langerhans cells in the pathogenesis of skin infectious diseases is well studied; however, there are few articles addressing involvement of factor XIIIa-positive dermal dendrocytes (FXIIIa+ DD) in such processes. FXIIIa+ DDs are bone marrow-monocytic lineage-derived cells and members of the skin immune system. Due to their immune phenotype and functional characteristics, they are considered complementary cells to Langerhans cells in the process of antigen presentation and inducing immune response. To verify the interaction between FXIIIa+ DD and Leishmania amastigotes, 22 biopsies of American tegumentary leishmaniasis (ATL) skin lesions were subjected to double staining technique with anti-factor XIIIa and anti-Leishmania antibodies. FXIIIa+ DDs were hypertrophic and abundant in the cutaneous reaction of ATL. FXIIIa+ DDs harboring parasites were observed in I I of 22 skin biopsies. The data obtained suggest that FXIIIa+ DD plays a role in the pathogenesis of ATL skin lesion as host cell, immune effector, and/or antigen-presenting cell.

Current Patient Management of Chronic Myeloid Leukemia in Latin America A Study by the Latin American Leukemia Net (LALNET)

BACKGROUND: Treatment recommendations have been developed for management of patients with chronic myeloid leukemia (CML). METHODS: A 30-item multiple-choice questionnaire was administered to 435 hematologists and oncohematologists in 16 Latin American countries. Physicians self-reported their diagnostic, therapeutic, and disease management strategies. RESULTS: Imatinib is available as initial therapy to 92% of physicians, and 42% of physicians have access to both second-generation tyrosine kinase inhibitors. Standard-dose imatinib is the preferred initial therapy for most patients, but 20% would manage a young patient initially with an allogeneic stem cell transplant from a sibling donor, and 10% would only offer hydroxyurea to an elderly patient. Seventy-two percent of responders perform routine cytogenetic analysis for monitoring patients on therapy, and 59% routinely use quantitative polymerase chain reaction. For patients who fail imatinib therapy, 61% would increase the dose of imatinib before considering change to a second-generation tyrosine kinase inhibitor, except for patients aged 60 years, for whom a switch to a second-generation tyrosine kinase inhibitor was the preferred choice. CONCLUSIONS: The answers to this survey provide insight into the management of patients with CML in Latin America. Some deviations from current recommendations were identified. Understanding the treatment patterns of patients with CML in broad population studies is important to identify needs and improve patient care. Cancer 2010;116:4991-5000. (C) 2070 American Cancer Society.

Evaluation of the prognostic significance of serum galectin-3 in American Joint Committee on Cancer stage III and stage IV melanoma patients

Galectin-3 (Gal-3) is a member of the P-galactoside-binding lectins family and has been implicated in angiogenesis, tumor invasion, and metastatic process in vitro and in vivo. As we showed recently that advanced melanoma patients presented high serum level of Gal-3, we investigated the association of this protein with the outcome of melanoma patients. Whether this protein could be a biomarker has riot been assessed, and we compared the prognostic value of serum Gal-3 in multivariate analysis with lactate dehydrogenase, C-reactive protein and S100B. We conclude that Gal-3 could be of prognostic value in melanoma patients; more precisely, this protein has a strong independent prognostic signification with a cut-off value of 10 ng/ml. After these data, we believe that serum Gal-3 measurement can have an important role in the follow-up and management of advanced American Joint Commission on Cancer stage III and stage IV melanoma patients. Further studies will uncover whether Gal-3 will be able to open new therapeutic perspectives. Melanoma Res 19:316-320 (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Comparison of clinical features and drug therapies among European and Latin American patients with juvenile dermatomyositis

Objective To compare the demographic features, presenting manifestations, diagnostic investigations, disease course, and drug therapies of children with juvenile dermatomyositis (JDM) followed in Europe and Latin America. Methods Patients were inception cohorts seen between 1980 and 2004 in 27 paediatric rheumatology centres. The following information was collected through the review of patient charts: sex; age at disease onset; date of disease onset and diagnosis; onset type; presenting clinical features; diagnostic investigations; course type; and medications received during disease course. Results Four hundred and ninety patients (65.5% females, mean onset age 7.0 years, mean disease duration 7.7 years) were included. Disease presentation was acute or insidious in 57.1% and 42.9% of the patients, respectively. The course type was monophasic in 41.3% of patients and chronic polycyclic or continuous in 58.6% of patients. The more common presenting manifestations were muscle weakness (84.9%), Gottron`s papules (72.9%), heliotrope rash (62%), and malar rash (56.7%). Overall, the demographic and clinical features of the 2 continental cohorts were comparable. European patients received more frequently high-dose intravenous methylprednisolone, cyclosporine, cyclophosphamide, and azathioprine, while methotrexate and antimalarials medications were used more commonly by Latin American physicians. Conclusion The demographic and clinical characteristics of JDM are similar in European and Latin American patients. We found, however, several differences in the use of medications between European and Latin American paediatric rheumatologists.

The Provisional Paediatric Rheumatology International Trials Organisation/American College of Rheumatology/European League Against Rheumatism disease activity core set for the evaluation of response to therapy in juvenile dermatomyositis: A prospective validation study

Objective. To validate a core set of outcome measures for the evaluation of response to treatment in patients with juvenile dermatomyositis (DM). Methods. In 2001, a preliminary consensus-derived core set for evaluating response to therapy in juvenile DM was established. In the present study, the core set was validated through an evidence-based, large-scale data collection that led to the enrollment of 294 patients from 36 countries. Consecutive patients with active disease were assessed at baseline and after 6 months. The validation procedures included assessment of feasibility, responsiveness, discriminant and construct ability, concordce in the evaluation of response to therapy between physicians and parents, redundancy, internal consistency, and ability to predict a therapeutic response. Results. The following clinical measures were found to be feasible, and to have good construct validity, discriminative ability, and internal consistency; furthermore, they were not redundant, proved responsive to clinically important changes in disease activity, and were associated strongly with treatment outcome and thus were included in the final core set: 1) physician`s global assessment of disease activity, 2) muscle strength, 3) global disease activity measure, 4) parent`s global assessment of patient`s well-being, 5) functional ability, and 6) health-related quality of life. Conclusion. The members of the Paediatric Rheumatology International Trials Organisation, with the endorsement of the American College of Rheumatology and the European Leauge Against Rheumatism, propose a core set of criteria for the evaluation of response of therapy that is scientifically and clinically relevant and statistically validated. The core set will help standardize the conduct and reporting of clinical trials and assist practitioners in deciding whether a child with juvenile DM has responded adequately to therapy.

Nasal allergies in the Latin American population: Results from the Allergies in Latin America survey

Allergies in Latin America is the first cross-national survey that describes the symptoms, impact, and treatment of nasal allergies (NAs) in individuals >= 4 years old in Latin America (LA). In total, 22,012 households across the Latin American countries of Argentina, Brazil, Chile, Colombia, Ecuador, Mexico, Peru, and Venezuela were screened for children, adolescents, and adults with a diagnosis of NA and either symptoms or treatment in the past 12 months. A total of 1088 adults and 457 children and adolescents were included and the sample was probability based to ensure valid statistical inference to the population. Approximately 7% of the LA population was diagnosed with NAs with two of three respondents stating that their allergies were seasonal or intermittent in nature. A general practice physician or otolaryngologist diagnosed the majority of individuals surveyed. Nasal congestion was the most common and bothersome symptom of NAs. Sufferers indicated that their symptoms affected productivity and sleep and had a negative impact on quality of life. Two-thirds of patients reported taking some type of medication for their NAs, with a roughly equal percentage of patients reporting taking over-the-counter versus prescription medications. Changing medications was most commonly done in those reporting inadequate efficacy. The most common reasons cited for dissatisfaction with current medications were related to inadequate effectiveness, effectiveness wearing off with chronic use, failure to provide 24-hour relief, and bothersome side effects (e.g., unpleasant taste and retrograde drainage into the esophagus). Findings from this cross-national survey on NAs have confirmed a high prevalence of physician-diagnosed NAs and a considerable negative impact on daily quality of life and work productivity as well as substantial disease management challenges in LA. Through identification of disease impact on the LA population and further defining treatment gaps, clinicians in LA may better understand and treat NAs, thus leading to improvements in overall patient satisfaction and quality of life. (Allergy Asthma Proc 31:S9-S27, 2010; doi: 10.2500/aap.2010.31.3347)