Immunogenicity of a killed Leishmania vaccine with saponin adjuvant in dogs

Cellular and humoral immune responses of dogs to a candidate vaccine, composed of Leishmania braziliensis promastigote protein plus saponin as adjuvant, have been investigated as a pre-requisite to understanding the mechanisms of immunogenicity against canine visceral leishmaniasis (CVL). The candidate vaccine elicited strong antigenicity related to the increases of anti-Leishmania IgG isotypes, together with higher levels of lymphocytes, particularly of circulating CD8(+) T-lymphocytes and Leishmania chagasi antigen-specific CD8(+) T-lymphocytes. As indicated by the intense cell proliferation and increased nitric oxide production during in vitro stimulation by L. chagasi soluble antigens, the candidate vaccine elicited an immune activation status potentially compatible with effective control of the etiological agent of CVL.     

Correction approach for underreporting of deaths and hospital admissions due to ill-defined causes

OBJECTIVE: To propose a correction approach for underreporting and relocation of ill-defined causes of morbidity and mortality in the National Health System Mortality and Hospital Information Systems. METHODS: Modified James-Stein empirical Bayes estimators for events in delimited geographic areas were applied as a correction approach for underreporting in Brazilian municipalities in 2001. RESULTS: There was an increase of 55,671 deaths in the Mortality Information System, an underreporting correction of 5.85%. It was more effective at the age groups under five (8.1%) and 70 years old and more (6.4%); for neonatal (8.7%) and ill-defined (8.0%) causes of death; and in the states of Maranh?o (10.6%), Bahia (9.5%) and Alagoas (8.8%). Relocation of ill-defined causes of mortality changed the structure of proportional mortality in the Northern and Northeastern regions, and increased the proportion of deaths due to cardiovascular diseases and reduced those due to external and neonatal causes. Relocation of ill-defined causes of hospital admissions did not affect hospital proportional morbidity. CONCLUSIONS: The results of underreporting correction were consistent with previous studies, in terms of age groups, causes and geographic areas. Relocation of ill-defined causes of death was spatially consistent. The approach studied may be applicable on Brazilian Health Information since it can be implemented in computational algorithms. Some improvements, however, may be considered, like estimation approaches based on time-space event distribution.     

Hearing screening in a public hospital in Belo Horizonte, Minas Gerais State, Brazil: hearing impairment and risk factors in neonates and infants

The objective of this study was to estimate the prevalence of hearing impairment in children in a public hospital in Belo Horizonte, Minas Gerais, Brazil, and to investigate the association with risk factors described in the literature. This study was cross-sectional and retrospective and analyzed 798 newborns and infants evaluated in the Universal Neonatal Hearing Screening Program from June 2002 to December 2003. The risk factors established by the Joint Committee on Infant Hearing in 1994 and Azevedo in 1996 were studied, besides prematurity. Prevalence of hearing impairment was 1.8% (15 cases). A multivariate logistic regression analysis was used to verify associations between risk factors and hearing impairment, showing a significant statistical association (p < 0.05) between hearing loss and suspicion of hearing loss by relatives, hyperbilirubinemia (serum level requiring exchange transfusion), ototoxic drugs, and low birth weight. A significant prevalence of hearing impairment in neonates and infants was confirmed. Attention should thus be focused on risk factors for hearing impairment, using hearing programs that ensure prevention, early detection, and intervention.     

Universal health systems and territory: challenges for a regional policy in the Brazilian Legal Amazon

This article presents the results of a study on Federal health policy in the Brazilian Legal Amazon (BLA) from 2003 to 2005, aimed at backing the development of regional health policies. The region has peculiar dynamics, an extensive border area, and adverse social indicators. The methodology included documental and financial analysis, participatory observation, interviews with heads of various Federal Ministries and State and Municipal health secretaries from the BLA; characterization of geographic situations in the BLA; and field studies in 15 municipalities. Institutional consolidation of health policy proved to be low in the Amazon during the study period, due to structural, institutional, and political difficulties. The identification of six geographic situations was useful for systematizing land use differences with repercussions on health, and which should be considered when implementing public policies. There is a certain gap between Federal actions and territorial dynamics, expressed as a mismatch between the current policy and its recognition by local administrators. In addition to establishing a regional policy for the Amazon, there is an evident need for differentiated policies within the region.     

Mycobacterium tuberculosis drug resistance in HIV patients in Baixada Santista, São Paulo, Brazil

Since the early 1990s, an increase in Mycobacterium tuberculosis drug resistance has been reported, with high prevalence among HIV+ patients. We evaluated the sensitivity patterns of M. tuberculosis, resistance rate, and predisposing factors among HIV+ patients in Santos, S?o Vicente, Cubat?o, Praia Grande, and Guarujá, S?o Paulo State, Brazil. The medical charts of 301 patients with positive cultures for M. tuberculosis from 1993 to 2003 were reviewed. Resistance occurred in 57 patients (18.9%), as follows: 32 (10.6%) displayed multidrug-resistant tuberculosis (resistant to at least Rifampicin and Isoniazid); 4 (1.3%) were resistant to two or more drugs; and 21 (7%) were resistant to a single drug. Acquired resistance was observed in 70.1% of cases. Drug resistance was significantly associated with previous tuberculosis treatment, duration of HIV diagnosis, and previous hospitalization. In logistic regression analysis, only previous tuberculosis treatment adjusted by age remained as an independent risk factor (OR = 5.49; 95%CI: 2.60-11.60). Drug resistance to at least one drug in 18.9% and multidrug resistance in 10.6% of cases highlight the relevance of this problem in HIV patients in the Baixada Santista.     

Serum lipoprotein(a) concentrations and alcohol consumption in hypertension: possible relevance for cardiovascular damage

OBJECTIVES: To evaluate the relationships between alcohol intake and serum lipoprotein(a) [Lp(a)], a powerful predictor of organ damage, in patients with essential hypertension with a wide range of alcohol intake, and to investigate whether the association between alcohol intake and serum Lp(a) concentrations occurs over the entire spectrum of apo(a) phenotypes. DESIGN: Cross-sectional study of a case series. SETTING: University medical centre. PATIENTS: Four hundred and two patients with untreated essential hypertension recruited at a hypertension clinic. MAIN OUTCOME MEASURES: Serum Lp(a) concentrations, apo(a) isoforms, alcohol consumption, smoking habits and cardiovascular status. RESULTS: No difference in Lp(a) concentrations was observed between teetotalers and occasional drinkers. Light drinkers (1-20 g/day ethanol), moderate drinkers (21-50 g/day), and heavy drinkers (> 50 g/day) had, respectively, 21, 26 and 57% lower median Lp(a) concentrations than teetotalers and occasional drinkers. Similar findings were obtained when male and female patients were analysed separately. Log Lp(a) concentrations were inversely and independently correlated with alcohol consumption in both men and women with hypertension. The frequency distributions of apo(a) isoforms and liver function parameters were comparable across the different alcohol intake groups. Patients with evidence of cardiovascular damage had greater concentrations of serum Lp(a) and higher frequency of low-molecular weight apo(a) isoforms as compared with patients without such evidence. CONCLUSIONS: Serum Lp(a) is inversely and dose-dependently related with alcohol intake in patients with hypertension, and this relationship is independent of the size distribution of apo(a) isoforms. Reduction of Lp(a) concentrations by regular consumption of alcohol might favourably affect the atherosclerotic risk profile of patients with hypertension and thereby decrease cardiovascular morbidity.     

Glucose Metabolism and Visceral Fat in GH Deficient Adults: Two Years of GH-Replacement

The aim of this study was to evaluate the effect of 24 months of growth hormone (GH) replacement on glucose metabolism and visceral fat in 17 adults with GH deficiency: 9 men and 8 women; age 40 ± 1.8 yr. [range 20–61] and body mass index 25 ± 0.8 Kg/m². Glucose metabolism was evaluated by a standard oral glucose tolerance test (OGTT), by the homeostatic model assessment (HOMA) insulin resistance index and by the insulin sensitivity index (ISI)-composite derived from the OGTT. Visceral fat was evaluated by CT scan. Twenty-four months of GH replacement induced an increase in the prevalence of abnormal glucose tolerance, with significant progressive increment in 2h-OGTT insulin levels at 3, 12 and 24 months (p = 0.005). Plasma glucose levels and ISI-composite did not alter during the study. HOMA-IR index increased only in the group of patients (n = 8) who had abnormal OGTT at 24 months (p = 0.012). Visceral fat reduced at month 12 and remained decreased until the end of the study (p = 0.009). In conclusion, the present study suggests that adults with GH deficiency after twenty-four months of GH replacement developed abnormal glucose tolerance, probably due to an increase in insulin resistance, associated with higher insulin levels, despite favorable alterations in body composition. Research grant-FAPER. Senior researcher-CNPQ.     

Uteroglobin-related protein 1 gene -112G/a polymorphism and atopic asthma in Sicilian children.

The secretory protein, uteroglobin-related protein 1 (UGRP1), is expressed mainly in the lung and trachea and recently has been implicated in asthma. The -112G to A transition in the promoter was reported to be associated with asthma in the Japanese population. However, this has not been replicated in other studies. The aim of this study was to find the association of the UGRP1 gene polymorphism with atopic asthma in the Sicilian population. We conducted a transmission disequilibrium test (TDT) in 73 trios identified through 113 pediatric patients being treated for asthma. A case-control study also was performed by comparing the 113 unrelated asthmatic children and 230 unrelated healthy Italian subjects (121 children and 109 adults). The -112 G/A polymorphism was genotyped by the polymerase chain reaction-restriction fragment length polymorphism method and direct sequencing. The TDT revealed that the -112A allele was not preferentially transmitted from the parents to asthmatic offspring (chi-square = 3.08; p = NS). Neither the presence of at least one A allele in an individual's genotype (sum of the G/A and A/A genotype) nor the -112A allele was more prevalent among the asthma subjects than among the control subjects. Our results suggest that the -112G/A polymorphism does not play a significant role in the genetic predisposition of the UGRP1 gene in atopic asthma in the Sicilian population.     

Further investigations on the expression of HLA-DR, CD33 and CD13 surface antigens in purified bone marrow and peripheral blood CD34± haematopoietic progenitor cells

Summary. We evaluated the HLA-DR, CD33 and CD13 antigen expression on CD34± haematopoietic progenitor cells (HPC) isolated from the bone marrow (BM) and peripheral blood (PB) of normal donors. The majority of both BM and PB CD34± HPC expressed CD13 and HLA-DR. The coexpression of CD34 and CD33 was found in a minor CD34± subset. After 7 d of culture in the presence of interleukin-3 and granulocyte-macrophage colony-stimulating factor, CD33 expression was detected in about 50% of HPC. At this point CD34 antigen expression was lost and CD13 and HLA-DR expression was partially lost. After 14 d of culture, the majority of HPC were CD33±. HPC maintained the capacity to generate colony forming unit granulocyte-macrophage but they lost the capacity to generate burst forming unit-erythroid. A correlation was found between the percentage of CD34±/HLA-DR± cells and the total number of colony forming cells in unfractionated samples from BM and PB of patients with malignancies. These studies demonstrate that, in normal conditions, only a minor subset of CD34± cells coexpress CD33 antigen either in BM or in PB and CD33 antigen is a lineage marker which is coexpressed with HLA-DR and CD13 on a progenitor committed to the granulocytic-macrophagic lineage.     

Serum C-reactive protein and cognitive function in healthy elderly Italian community dwellers

BACKGROUND: Chronic low-grade inflammation, as measured with the peripheral serum marker C-reactive protein (sCRP), may be a risk factor for dementia in elderly persons. METHODS: The relationship between sCRP and score on the Mini-Mental State Examination (MMSE), a commonly used screening cognitive measure, was investigated in 540 well functioning, healthy, and cognitively normal elders (age 73 +/- 6 years). Sociodemographic status, lifestyle, health status, traditional and nontraditional cardiovascular risk factors including plasma total homocysteine (tHcy), and other peripheral blood markers of vascular inflammation (leukocyte count, serum albumin, and plasma fibrinogen) were also assessed. RESULTS: Risk for having sCRP in the highest decile (>0.7 mg/dl) was significantly higher in individuals with MMSE score 24-25 (odds ratio = 3.07, 95% confidence interval, 1.2-7.9) and 26-28 (odds ratio = 2.10, 95% confidence interval, 1.1-3.9) compared with those scoring above 28 (reference group). Results were unaffected by adjustment for all potential confounders. No association was found between MMSE and peripheral markers of vascular inflammation other than sCRP, but lower MMSE scores were also independently associated with hyperhomocysteinemia (plasma tHcy > 15 mmol/L). CONCLUSION: In healthy, cognitively normal elderly community dwellers, increased sCRP levels are associated with concurrent cognitive impairment as measured by MMSE. The association is independent of sociodemographic status, lifestyle, health status, and traditional and nontraditional cardiovascular risk factors including hyperhomocysteinemia. Results support the hypothesis that chronic low-grade inflammation may be involved in age-related cognitive impairment.