Shwachman-Kulczycki score still useful to monitor cystic fibrosis severity

INTRODUCTION: The Shwachman-Kulczycki score was the first scoring system used in cystic fibrosis to assess disease severity. Despite its subjectivity, it is still widely used. OBJECTIVE: To study correlations among forced expiratory volume in one second (FEV1), chest radiography, chest computed tomography, 6-minute walk test, and Shwachman-Kulczycki score in patients with cystic fibrosis and to test whether the Shwachman-Kulczycki score is still useful in monitoring the severity of the disease. METHODS: A cross-sectional prospective study was performed to analyze the correlations (Spearman). Patients with clinically stable cystic fibrosis, aged 3-21 years, were included. RESULTS: 43 patients, 19F/24M, mean age 10.5 + 4.7 years, with a median Shwachman-Kulczycki score of 70 were studied. The median Brasfield and Bhalla scores were 17 and 10, respectively. The mean Z score for the 6-minute walk test was -1.1 + 1.106 and the mean FEV1 was 59 + 26 (as percentage of predicted values). The following significant correlations versus the Shwachman-Kulczycki score were found: FEV1 (r = 0.76), 6-minute walk test (r = 0.71), chest radiography (r = 0.71) and chest computed tomography (r = -0.78). When patients were divided according to FEV1, a statistically significantly correlation with the Shwachman-Kulczycki score was found only in patients with FEV1 <70% (r = 0.67). CONCLUSIONS: The Shwachman-Kulczycki score remains an useful tool for monitoring the severity of cystic fibrosis, adequately reflecting the functional impairment and chest radiography and tomography changes, especially in patients with greater impairment of lung function. When assessing patients with mild lung disease its limitations should be considered and its usefulness in such patients should be evaluated in larger populations.

Revised criteria for the assessment and interpretation of occlusal deviations in the deciduous dentition: a public health perspective

Dados secundários de uma amostra aleatória de pré-escolares brasileiros foram analisados com o objetivo de avaliar a prevalência de desvios oclusais na dentição decídua, que podem adversamente afetar a dentição permanente, com base em critérios revisados. Overjet e overbite apresentaram pontos de corte descritos na literatura para a remoção dos casos de má oclusão leve. Overjet > 3mm e overbite > 3mm afetaram 16% e 7% das crianças, respectivamente. No plano sagital foram consideradas apenas as taxas de desvios bilaterais: relação molar em degrau distal (9,7%) e mesial (6,0%); relação dos caninos Classe 2 (11,0%) e Classe 3 (2,9%). Para os demais desvios não foram relatados na literatura critérios de severidade. Valores brutos de mordida aberta anterior (27,9%); mordida cruzada posterior (11,3%); apinhamento dentário maxilar (7,0%) e mandibular (11,3%) foram registrados. A avaliação da má oclusão na dentição decídua deve considerar a severidade dos desvios para a identificação de casos e não-casos de relevância em saúde pública. Enfatiza-se a necessidade de maior consenso e melhora na interpretação de dados epidemiológicos sobre a má oclusão nesse estágio de desenvolvimento

TCF7L2 Polymorphism rs7903146 Is Associated with Coronary Artery Disease Severity and Mortality

Background: TCF7L2 polymorphisms have been consistently associated with type 2 diabetes mellitus in different populations and type 2 diabetes mellitus is a major risk factor for cardiovascular disease, especially coronary artery disease. This study aimed to evaluate the association between TCF7L2 polymorphism rs7903146 and coronary artery disease in diabetic and non-diabetic subjects. Methods and Results: two populations were studied in order to assess severity of coronary artery disease and cardiovascular events incidence. Eight-hundred and eighty nine subjects who were referred for cardiac catheterization for coronary artery disease diagnosis were cross-sectionally evaluated for coronary lesions (atherosclerotic burden) and 559 subjects from the MASS-II Trial were prospectively followed-up for 5 years and assessed for major cardiovascular events incidence. As expected, rs7903146 T allele was associated with diabetes. Although diabetic patients had a higher prevalence of coronary lesions, no association between TCF7L2 genotype and coronary lesions was found in this subgroup. However, non-diabetic individuals carrying the T allele were associated with a significantly higher frequency of coronary lesions than non-diabetic non-carriers of the risk allele (adjusted OR = 2.32 95% CI 1.27-4.24, p = 0.006). Moreover, presence of multi-vessel coronary artery disease was also associated with the CT or TT genotypes in non-diabetics. Similarly, from the prospective sample analysis, non-diabetics carrying the CT/TT genotypes had significantly more composite cardiovascular end-points events than CC carriers (p = 0.049), mainly due to an increased incidence of death (p = 0.004). Conclusions: rs7903146 T allele is associated with diabetes and, in non-diabetic individuals, with a higher prevalence and severity of coronary artery disease and cardiovascular events. name of registry site (see list below), registration number, trial registration URL in brackets.

Prognostic factors for progression of liver structural lesions in chronic hepatitis C patients

AIM: To evaluate the epidemiological, clinical, laboratory and histological variables capable of predicting the progression of hepatic structural disturbances in chronic hepatitis C patients during the time interval between two liver biopsies. METHODS: Clinical charts of 112 chronic hepatitis C patients were retrospectively analyzed, whereas liver biopsies were revised. Immunohistochemical detection of interferon receptor was based on the Envision-Peroxidase System. RESULTS: In the multivariate analysis, the variables in the age at first biopsy, ALT levels, presence of lymphoid aggregates and siderosis were the determinants of the best model for predicting the severity of the disease. The direct progression rate of hepatic structural lesions was significantly higher in untreated patients, intermediate in treated non-responders and lower in treated responders to antiviral therapy (non-treated vs responders, 0.22 +/- 0.50 vs -0.15 +/- 0.46, P = 0.0053). Immuno-expression of interferon receptor is not a relevant factor. CONCLUSION: The best predictors of the progression of fibrosis are age at the first liver biopsy, extent of ALT elevation, inflammation at liver histology and hepatic siderosis. Antiviral treatment is effective in preventing the progression of liver structural lesions in chronic hepatitis C patients. (C) 2008 WJG. All rights reserved.

Incidence and predictors of severe liver fibrosis in HIV-infected patients with chronic hepatitis C in Brazil

The aim of this study was to examine the incidence and factors associated with the severity of liver fibrosis in 234 coinfected patients in Brazil. Patients were cared for in our clinic, from 1996 to 2004. Eligible patients were defined as patients with documented HIV and hepatitis C virus (HCV) infections and had previously undergone a liver biopsy. Patients with persistently normal alanine aminotransferase (ALT) were also included. The variables selected for study were age, gender, risk category, history of high alcohol consumption, CD4(+) T cell count, antiretroviral therapy usage, HCV genotype and duration of HCV infection. Stage of fibrosis was scored as follows: F0, no fibrosis; F1, portal fibrosis with no septa; F2, portal fibrosis with few septa; F3, bridging fibrosis with many septa; and F4, cirrhosis. The liver fibrosis stage was F3 in 39 (16.6%) and F4 in 20(8.5%) patients. Among patients with normal ALT, the liver fibrosis stage was F3-F4 in three patients (5.6%). Predictors of severe liver fibrosis (17344) by multivariate analysis were age (older patients) and genotype 3 (genotype I odds ratio [OR], 0.28; 95% confidence interval [0], 0.12 0.65). In summary, in the present study severe liver fibrosis was found in 25% of our patients and was associated with an age of more than 38 years at the time of liver biopsy as well as, HCV genotype 3. No differences were found with respect to CD4(+) T cell counts although patients with a CD4(+) T cell count greater than 50 were excluded.

BALB/c Mice Infected with Antimony Treatment Refractory Isolate of Leishmania braziliensis Present Severe Lesions due to IL-4 Production

Background: Leishmania braziliensis is the main causative agent of cutaneous leishmaniasis in Brazil. Protection against infection is related to development of Th1 responses, but the mechanisms that mediate susceptibility are still poorly understood. Murine models have been the most important tools in understanding the immunopathogenesis of L. major infection and have shown that Th2 responses favor parasite survival. In contrast, L. braziliensis-infected mice develop strong Th1 responses and easily resolve the infection, thus making the study of factors affecting susceptibility to this parasite difficult. Methodology/Principal Findings: Here, we describe an experimental model for the evaluation of the mechanisms mediating susceptibility to L. braziliensis infection. BALB/c mice were inoculated with stationary phase promastigotes of L. braziliensis, isolates LTCP393(R) and LTCP15171(S), which are resistant and susceptible to antimony and nitric oxide (NO), respectively. Mice inoculated with LTCP393(R) presented larger lesions that healed more slowly and contained higher parasite loads than lesions caused by LTCP15171(S). Inflammatory infiltrates in the lesions and production of IFN-gamma, TNF-alpha, IL-10 and TGF-beta were similar in mice inoculated with either isolate, indicating that these factors did not contribute to the different disease manifestations observed. In contrast, IL-4 production was strongly increased in LTCP393(R)-inoculated animals and also arginase I (Arg I) expression. Moreover, anti-IL-4 monoclonal antibody (mAb) treatment resulted in decreased lesion thickness and parasite burden in animals inoculated with LTCP393(R), but not in those inoculated with LTCP15171(S). Conclusion/Significance: We conclude that the ability of L. braziliensis isolates to induce Th2 responses affects the susceptibility to infection with these isolates and contributes to the increased virulence and severity of disease associated with them. Since these data reflect what happens in human infection, this model could be useful to study the pathogenesis of the L. braziliensis infection, as well as to design new strategies of therapeutic intervention.

T cells, adhesion molecules and modulation of apoptosis in visceral leishmaniasis glomerulonephritis

Background: Immune complex deposition is the accepted mechanism of pathogenesis of VL glomerulopathy however other immune elements may participate. Further in the present study, no difference was seen between immunoglobulin and C3b deposit intensity in glomeruli between infected and non-infected dogs thus T cells, adhesion molecules and parameters of proliferation and apoptosis were analysed in dogs with naturally acquired VL from an endemic area. The dog is the most important domestic reservoir of the protozoa Leishmania (L.) chagasi that causes visceral leishmaniasis (VL). The similarity of VL manifestation in humans and dogs renders the study of canine VL nephropathy of interest with regard to human pathology. Methods: From 55 dogs with VL and 8 control non-infected dogs from an endemic area, kidney samples were analyzed by immunohistochemistry for immunoglobulin and C3b deposits, staining for CD4+ and CD8+ T cells, ICAM-1, P-selectin and quantified using morphometry. Besides proliferation marker Ki-67, apoptosis markers M30 and TUNEL staining, and related cytokines TNF-alpha, IL-1 alpha were searched and quantified. Results: We observed similar IgG, IgM and IgA and C3b deposit intensity in dogs with VL and non-infected control dogs. However we detected the Leishmania antigen in cells in glomeruli in 54, CD4+ T cells in the glomeruli of 44, and CD8+ T cells in 17 of a total of 55 dogs with VL. Leishmania antigen was absent and T cells were absent/scarse in eight non-infected control dogs. CD 4+ T cells predominate in proliferative patterns of glomerulonephritis, however the presence of CD4+ and CD8+ T cells were not different in intensity in different patterns of glomerulonephritis. The expression of ICAM-1 and P-selectin was significantly greater in the glomeruli of infected dogs than in control dogs. In all patterns of glomerulonephritis the expression of ICAM-1 ranged from minimum to moderately severe and P-selectin from absent to severe. In the control animals the expression of these molecules ranged from absent to medium intensity. It was not observed any correlation between severity of the disease and these markers. There was a correlation between the number of Leishmania antigen positive cells and CD4+ T cells, and between the number of CD4+ T cells and CD8+ T cells. In dogs presenting different histopathological patterns of glomerulonephritis, parameters of proliferation and apoptosis were studied. Ki-67, a proliferative marker, was not detected locally, but fewer apoptotic cells and lower TNF-alpha expression were seen in infected animals than in non-infected controls. Conclusion: Immunopathogenic mechanisms of VL glomerulonephritis are complex and data in the present study suggest no clear participation of immunoglobulin and C3b deposits in these dogs but the possible migration of CD4+ T cells into the glomeruli, participation of adhesion molecules, and diminished apoptosis of cells contributing to determine the proliferative pattern of glomerulonephritis in VL.

A New Mouse Model for Marfan Syndrome Presents Phenotypic Variability Associated with the Genetic Background and Overall Levels of Fbn1 Expression

Marfan syndrome is an autosomal dominant disease of connective tissue caused by mutations in the fibrillin-1 encoding gene FBN1. Patients present cardiovascular, ocular and skeletal manifestations, and although being fully penetrant, MFS is characterized by a wide clinical variability both within and between families. Here we describe a new mouse model of MFS that recapitulates the clinical heterogeneity of the syndrome in humans. Heterozygotes for the mutant Fbn1 allele mg Delta(loxPneo), carrying the same internal deletion of exons 19-24 as the mg Delta mouse model, present defective microfibrillar deposition, emphysema, deterioration of aortic wall and kyphosis. However, the onset of a clinical phenotypes is earlier in the 129/Sv than in C57BL/6 background, indicating the existence of genetic modifiers of MFS between these two mouse strains. In addition, we characterized a wide clinical variability within the 129/Sv congenic heterozygotes, suggesting involvement of epigenetic factors in disease severity. Finally, we show a strong negative correlation between overall levels of Fbn1 expression and the severity of the phenotypes, corroborating the suggested protective role of normal fibrillin-1 in MFS pathogenesis, and supporting the development of therapies based on increasing Fbn1 expression.

Phylogenetic position of the acariform mites: sensitivity to homology assessment under total evidence

Background: Mites (Acari) have traditionally been treated as monophyletic, albeit composed of two major lineages: Acariformes and Parasitiformes. Yet recent studies based on morphology, molecular data, or combinations thereof, have increasingly drawn their monophyly into question. Furthermore, the usually basal (molecular) position of one or both mite lineages among the chelicerates is in conflict to their morphology, and to the widely accepted view that mites are close relatives of Ricinulei. Results: The phylogenetic position of the acariform mites is examined through employing SSU, partial LSU sequences, and morphology from 91 chelicerate extant terminals (forty Acariformes). In a static homology framework, molecular sequences were aligned using their secondary structure as guide, whereby regions of ambiguous alignment were discarded, and pre-aligned sequences analyzed under parsimony and different mixed models in a Bayesian inference. Parsimony and Bayesian analyses led to trees largely congruent concerning infraordinal, well-supported branches, but with low support for inter-ordinal relationships. An exception is Solifugae + Acariformes (P. P = 100%, J. = 0.91). In a dynamic homology framework, two analyses were run: a standard POY analysis and an analysis constrained by secondary structure. Both analyses led to largely congruent trees; supporting a (Palpigradi (Solifugae Acariformes)) clade and Ricinulei as sister group of Tetrapulmonata with the topology (Ricinulei (Amblypygi (Uropygi Araneae))). Combined analysis with two different morphological data matrices were run in order to evaluate the impact of constraining the analysis on the recovered topology when employing secondary structure as a guide for homology establishment. The constrained combined analysis yielded two topologies similar to the exclusively molecular analysis for both morphological matrices, except for the recovery of Pedipalpi instead of the (Uropygi Araneae) clade. The standard (direct optimization) POY analysis, however, led to the recovery of trees differing in the absence of the otherwise well-supported group Solifugae + Acariformes. Conclusions: Previous studies combining ribosomal sequences and morphology often recovered topologies similar to purely morphological analyses of Chelicerata. The apparent stability of certain clades not recovered here, like Haplocnemata and Acari, is regarded as a byproduct of the way the molecular homology was previously established using the instrumentalist approach implemented in POY. Constraining the analysis by a priori homology assessment is defended here as a way of maintaining the severity of the test when adding new data to the analysis. Although the strength of the method advocated here is keeping phylogenetic information from regions usually discarded in an exclusively static homology framework; it still has the inconvenience of being uninformative on the effect of alignment ambiguity on resampling methods of clade support estimation. Finally, putative morphological apomorphies of Solifugae + Acariformes are the reduction of the proximal cheliceral podomere, medial abutting of the leg coxae, loss of sperm nuclear membrane, and presence of differentiated germinative and secretory regions in the testis delivering their products into a common lumen.

VEGF Promotes Malaria-Associated Acute Lung Injury in Mice

The spectrum of the clinical presentation and severity of malaria infections is broad, ranging from uncomplicated febrile illness to severe forms of disease such as cerebral malaria (CM), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pregnancy-associated malaria (PAM) or severe anemia (SA). Rodent models that mimic human CM, PAM and SA syndromes have been established. Here, we show that DBA/2 mice infected with P. berghei ANKA constitute a new model for malaria-associated ALI. Up to 60% of the mice showed dyspnea, airway obstruction and hypoxemia and died between days 7 and 12 post-infection. The most common pathological findings were pleural effusion, pulmonary hemorrhage and edema, consistent with increased lung vessel permeability, while the blood-brain barrier was intact. Malaria-associated ALI correlated with high levels of circulating VEGF, produced de novo in the spleen, and its blockage led to protection of mice from this syndrome. In addition, either splenectomization or administration of the anti-inflammatory molecule carbon monoxide led to a significant reduction in the levels of sera VEGF and to protection from ALI. The similarities between the physiopathological lesions described here and the ones occurring in humans, as well as the demonstration that VEGF is a critical host factor in the onset of malaria-associated ALI in mice, not only offers important mechanistic insights into the processes underlying the pathology related with malaria but may also pave the way for interventional studies.

Use of Hyaluronidase to Prevent Perineal Trauma During Spontaneous Births: A Randomized, Placebo-Controlled, Double-blind, Clinical Trial

Introduction: The purpose of this study was to compare the frequency and severity of perineal trauma during spontaneous birth with or without perineal injections of hyaluronidase (HAase). Methods: A randomized, placebo-controlled, double-blind clinical trial was conducted in a midwife-led, in-hospital birth center in Sao Paulo, Brazil. Primiparous women (N = 160) were randomly assigned to an experimental (n = 80) or control (n = 80) group. During the second stage of labor, women in the experimental group received an injection of 20.000 turbidity-reducing units of HAase in the posterior region of the perineum, and those in the control group received a placebo injection. The assessment of perineal outcome was performed by 2 independent nurse-midwives. A 1-tailed Fisher exact test was performed, and a P value < .025 was considered statistically significant. Results: Perineal integrity occurred in 34.2% of the experimental group and in 32.5% of the control group, which was not a statistically significant difference (P = .477). First-degree laceration was the most common trauma in the posterior region of the perineum in women in both groups (experimental = 56%, control = 42.6%). Severe perineal trauma occurred in 28.9% of the experimental group and 38.8% of the control group, which also was not a statistically significant difference (P =. 131). The depth of second-degree perineal lacerations in the experimental and control groups, measured by the Peri-Rule, was 1.9 cm and 2.3 cm, respectively. An episiotomy was performed in 11 women (experimental group = 3, control group = 8), and 4 (all in control group) had third-degree lacerations. Discussion: The use of injectable HAase did not increase the proportion of intact perineum and did not reduce the proportion of severe perineal trauma in our sample. J Midwifery Womens Health 2011; 56: 436-445 (C) 2011 by the American College of Nurse-Midwives.

Drip fungigation in early blight control of tomato

The aim was to verify if the fungigation via drip irrigation is an alternative to the conventional method of spraying on tomato for controlling early blight. Tomato plants (variety Santa Clara) were grown in pots inside a greenhouse. Fifty days after transplanting, the plants were inoculated with Alternaria solani and treated with four different fungicides: azoxystrobin (8 g 100 L(-1)), difeconazole (50 mL 100 L(-1)), metiram+piraclostrobin (200 g 100 L(-1)) and tebuconazole (100 mL 100 L(-1)) using two applications methods: conventional spraying and fiingigation dripping. The control plants did not receive fungicide application. To assess the severity of the disease, we used a rating scale expressed as the area under the disease progress curve (AUDPC) and production factors, such as number, weight and average diameter of the fruit and its productivity. The experimental design was completely randomized in factorial scheme 4 x 2 + 1 with eight replicates. Each plot had one plant in one pot. A 27% reduction in disease severity was observed when compared with the control plants, with no significant difference noted regarding the application method. The number of fruits did not statistically differ between the treatments. The average weight and diameter of the fruits were superior in the plants that had fungicide application compared to the control plant, reflecting an increase in productivity. Fungigation through water dripping is an alternative to the conventional method of spraying cultured tomatoes.

Copper sprays and windbreaks for control of citrus canker on young orange trees in southern Brazil

The benefit of windbreaks and copper sprays for control of citrus canker caused by Xanthomonas axonopodis pv. citri was investigated in a commercial citrus orchard located in a citrus canker endemic area in southern Brazil. Control of canker was evaluated as incidence and severity of lesions on foliage and by the effect on premature leaf and fruit drop for three production seasons. Effect of the treatments on fruit production was evaluated as incidence of citrus canker on prematurely abscised fruits and harvested fruits. Copper application significantly reduced damage to foliage and fruit, while windbreaks made little contribution to disease control. Copper sprays increased fruit yield for 3 years. This could be attributed to lower incidence of fruit with lesions and fewer fruits abscised due to canker infection. Incidence and severity on the leaves were inversely related to the number of fruits harvested per tree and directly related to the number of fruits abscised per tree. Published by Elsevier Ltd.

Viroid species associated with the bark-cracking phenotype of `Tahiti` acid lime in the State of Sao Paulo, Brazil

Viroids have been used as ""graft transmissible dwarfing agents"" (GTDA) in several countries, mainly to reduce growth of citrus trees, thus increasing their density in orchards. In the State of Sao Paulo, Brazil, plants of the acid lime `Tahiti` are usually grafted with a complex of GTDA, presumably viroids. The aim of the present work was the identification and molecular characterization of the viroids infecting trees of acid lime `Tahiti` displaying ""Quebra galho"" (bark-cracking). Viroids were identified and characterized by biological indexing in `Etrog` citron, Northern-blot hybridization, RT-PCR, cloning and complete sequencing of the RNA genomes. Citrus exocortis viroid (CEVd), Hop stunt viroid (HSVd) and Citrus dwarfing viroid (CDVd) were found in different combinations. Although we have not been able to infer a direct relationship between the agronomical performance and symptom severity with the presence of a specific viroid or viroid combination, the differences in the severity of ""Quebra-galho"" symptoms among different trees is probably associated with the presence (or absence) of CEVd, with its interaction with other viroids perhaps determining the different phenotypes observed in the field.

Development of Ramulosis Disease of Cotton Under Controlled Environment and Field Conditions

Colletotrichum gossypii var. cephalosporioides, the fungus that causes ramulosis disease of cotton, is widespread in Brazil and can cause severe yield loss. Because weather conditions greatly affect disease development, the objective of this work was to develop weather-based models to assess disease favorability. Latent period, incidence, and severity of ramulosis symptoms were evaluated in controlled environment experiments using factorial combinations of temperature (15, 20, 25, 30, and 35 degrees C) and leaf wetness duration (0, 4, 8, 16, 32, and 64 h after inoculation). Severity was modeled as an exponential function of leaf wetness duration and temperature. At the optimum temperature of disease development, 27 degrees C, average latent period was 10 days. Maximum ramulosis severity occurred from 20 to 30 degrees C, with sharp decreases at lower and higher temperatures. Ramulosis severity increased as wetness periods were increased from 4 to 32 h. In field experiments at Piracicaba, Sao Paulo State, Brazil, cotton plots were inoculated (10(5) conidia ml(-1)) and ramulosis severity was evaluated weekly. The model obtained from the controlled environment study was used to generate a disease favorability index for comparison with disease progress rate in the field. Hourly measurements of solar radiation, temperature, relative humidity, leaf wetness duration, rainfall, and wind speed were also evaluated as possible explanatory variables. Both the disease favorability model and a model based on rainfall explained ramulosis growth rate well, with R(2) of 0.89 and 0.91, respectively. They are proposed as models of ramulosis development rate on cotton in Brazil, and weather-disease relationships revealed by this work can form the basis of a warning system for ramulosis development.