Carlos Teixeira Brandt

Variants of CTGF are associated with hepatic fibrosis in Chinese, Sudanese, and Brazilians infected with Schistosomes

Abnormal fibrosis occurs during chronic hepatic inflammations and is the principal cause of death in hepatitis C virus and schistosome infections. Hepatic fibrosis (HF) may develop either slowly or rapidly in schistosome-infected subjects. This depends, in part, on a major genetic control exerted by genes of chromosome 6q23. A gene (connective tissue growth factor [CTGF]) is located in that region that encodes a strongly fibrogenic molecule. We show that the single nucleotide polymorphism (SNP) rs9402373 that lies close to CTGF is associated with severe HF (P = 2 × 10−6; odds ratio [OR] = 2.01; confidence interval of OR [CI] = 1.51–2.7) in two Chinese samples, in Sudanese, and in Brazilians infected with either Schistosoma japonicum or S. mansoni. Furthermore, SNP rs12526196, also located close to CTGF, is independently associated with severe fibrosis (P = 6 × 10−4; OR = 1.94; CI = 1.32–2.82) in the Chinese and Sudanese subjects. Both variants affect nuclear factor binding and may alter gene transcription or transcript stability. The identified variants may be valuable markers for the prediction of disease progression, and identify a critical step in the development of HF that could be a target for chemotherapy.

Autotransplant of spleen tissue in children with schistosomiasis: evaluation of splenic function after splenosis.

Autotransplantation of spleen tissue has been done, in the past ten years, in children with schistosomiasis mansoni with bleeding varices. The purposes of this investigation were: (1) to study the morphology and function of the remnant spleen tissue; (2) to quantify the production of tuftsin; and (3) to assess the immune response to pneumococcal vaccine of these patients. Twenty three children, who underwent splenectomy and autologous implantation of spleen tissue into the greater omentum were included in this investigation. The average postoperative follow-up is five years. Splenosis was proved by colloid liver-spleen scans. Search for Howell-Jolly bodies assessed the filtration function. Tuftsin and the titer of pneumococcal antibodies were quantified by ELISA. Splenosis was evident in all children; however, it was insufficient in two. Howell-Jolly bodies were found only in these two patients. The mean tuftsin serum concentration (335.0 +/- 29.8 ng/ml) was inside the normal range. The immune response to pneumococcal vaccination was adequate in 15 patients; intermediate in four; and inadequate in four. From the results the following conclusions can be drawn: splenosis was efficient in maintaining the filtration splenic function in more than 90% and produced tuftsin inside the range of normality. It also provided the immunologic splenic response to pneumococcal vaccination in 65% of the patients of this series.

Translocation of 99mTc labelled bacteria after intestinal ischemia and reperfusion

OBJETIVO: Isquemia e reperfusao do intestino delgado tem sido implicadas na quebra da barreira mucosa, na translocacao bacteriana e na ativacao de reacoes inflamatorias. Este estudo procurou avaliar se a Escherichia coli marcada com 99mTc transloca para linfonodos mesentericos, figado, baco, pulmao e soro de ratos submetidos a isquemia intestinal/reperfusao e se o tempo de reperfusao influencia o fenomeno. METODOS: Quarenta ratos Wistar foram submetidos a 45 minutos de isquemia intestinal atraves da oclusao da arteria mesenterica superior. A translocacao de bacterias marcadas para os diferentes orgaos e soro portal foi determinada em ratos apos reperfusao mesenterica por 30 minutos, 24 horas, sham e controles, usando contagem de radioatividade e formacao de unidades de colonias/grama de tecido (FUC/g). RESULTADOS: Todos os orgaos dos animais observados com 24 horas de reperfusao intestinal tiveram niveis maiores de radioatividade e culturas positivas (FUC/g) do que os orgaos dos ratos reperfundidos por 30 minutos, os controles, e os sham, com excecao do baco (p<0,01). CONCLUSAO: Os resultados indicaram que a isquemia e reperfusao intestinal resulta em translocacao bacteriana, mais intensamente apos 24 horas de reperfusao.

Barreiras para o acesso ao tratamento da catarata senil na Fundação Altino Ventura

PURPOSE: To identify the barriers in the access to treatment of senile cataract and to evaluate the patients costs in this process. METHODS: A survey of 101 patients who would undergo cataract surgery at Altino Ventura Foundation was performed using a questionnaire. The economical and social aspects of the whole process of treatment were evaluated. RESULTS: The principal barriers of cataract treatment were: fear of surgery, patients low income, the need for preoperative examinations and the number of times the patient had to return to the service (3.2±1.5), as well as the waiting time between the first examination and the surgery (3.2±2.6 months - Mean ±SEM). The examination costs varied from 5 to 170 reais (16.6±2.7 - Mean ±SEM). DISCUSSION: The main reasons for not seeking for cataract treatment, as the fear to undergo surgery and the lack of financial resources had been similar to other Brazilian institutions. The number of times that the patient had to return to the service increased the expenses of the patient and the difficulties faced by him. Altino Ventura Foundation mainly takes care of the poorest population of the State, therefore, the expenses of the patients with transportation and examinations become obstacles to the treatment of cataract. CONCLUSIONS: The fear of surgery and the patients low income and the social level of the institutions users were the principal barriers in the access to cataract treatment in this study. The need for preoperative examinations, sometimes unnecessary, contributes to a lower efficiency of the medical services offered to individuals of low income and social conditions. The surgery carried out at the same day of the cataract diagnosis makes the solution of the illness quickly possible, diminishing the number of times necessary for the patients return to health service from three or more, to only one.

Brain Magnetic Resonance Imaging Findings in Young Patients with Hepatosplenic Schistosomiasis Mansoni without Overt Symptoms

The purpose of this study was to describe the brain magnetic resonance imaging (MRI) findings in young patients with hepatosplenic schistosomiasis mansoni without overt neurologic manifestations. This study included 34 young persons (age range = 9-25 years) with hepatosplenic schistosomiasis mansoni who had been previously treated. Patients were scanned on a 1.5-T system that included multiplanar pre-contrast and post-contrast sequences, and reports were completed by two radiologists after a consensus review. Twenty (58.8%) patients had MRI signal changes that were believed to be related to schistosomiasis mansoni. Twelve of the 20 patients had small focal hyperintensities on T2WI in the cerebral white matter, and eight patients had symmetric hyperintense basal ganglia on T1WI. There was a high frequency of brain MRI signal abnormalities in this series. Although not specific, these findings may be related to schistosomiasis.

Autotransplantation of spleen tissue in children with mansonic schistosomiasis who underwent splenectomy: Evaluation of splenic residual functions

Transplante autologo de tecido esplenico e uma tentativa de manter as funcoes esplenicas quando esplenectomia esta indicado em criancas. Ele minimiza os riscos de septicemia fulminante apos esplenectomia e tem sido feito em criancas com hipertensao porta severa, devido a hepato-esplenomegalia esquistossomotica, que se submeteram a esplenectomia. Os objetivos da presente investigacao foram: estudar a morfologia do tecido esplenico residual; avaliar a funcao de filtracao da esplenose; e avaliar a resposta imune a vacinacao polivalente contra pneumococos destes pacientes. Vinte e tres criancas com hipertensao porta, devido a esquistossomose mansonica, que se submeteram a esplenectomia, ligadura da veia gastrica esquerda, autotransplante de tecido esplenico em bolsa no omento maior foram avaliadas para as funcoes esplenicas residuais. Cintilografia hepatoesplenica com enxofre coloidal marcado com Tc-99m foi usado para deteccao dos nodulos esplenicos. A pesquisa de corpusculos de Howell Jolly foi usada para avaliar a funcao de filtracao. A avaliacao da resposta de anticorpos contra pneumococos foi medida pelo metodo de Elisa. Esplenose foi evidente em todas as criancas, contudo, em dois, foi identificado menos de cinco nodulos esplenicos no omento maior, a qual foi considerada insuficiente. Corpusculos de Howell Jolly foram encontrados no sangue periferico somente nesses dois pacientes com esplenose menos evidente. A resposta imune foi adequada em quinze pacientes; foi intermediaria em quatro pacientes e inadequada em outros quatro. Transplante autologo de tecido esplenico em bolsa do omento maior foi considerado eficiente na manutencao da funcao esplenica em mais de 90% dos pacientes e da resposta imune a vacinacao contra pneumococos em aproximadamente 65% das criancas.

Surgical hepatosplenic schistosomiasis mansoni in children: a Doppler Duplex study of the portal vein and the hepatic artery

From January 1990 to September 1993, 25 children with hepatosplenic schistosomiasis mansoni and oesophageal varices underwent splenectomy, ligature of the left gastric vein and autoimplantation of 100 g of spleen into the great omentum at the University Hospital, Recife, Brazil. The diameters and the blood flow velocities of the portal vein and the hepatic artery were measured before and after surgery. A Doppler Duplex (Aloka 680) with a convex transductor of 3.5 MHz was used. Post-operative follow-up revealed (i) a significant decrease in the mean diameter of the portal vein from 12.6 +/- 2.1 mm to 9.6 +/- 1.9 mm, (ii) a significant increase in the mean diameter of the hepatic artery from 5.0 +/- 1.4 mm to 5.3 +/- 1.2 mm, (iii) a significant decrease in the mean blood flow velocity in the portal vein from 31.1 +/- 8.0 cm/s to 22.4 +/- 7.1 cm/s, and (iv) no significant change in blood flow velocity in the hepatic artery. The study supports the concept that surgical treatment for portal hypertension in patients with hepatosplenic schistosomiasis mansoni, which includes splenectomy, results in a decrease of venous portal blood flow to the liver associated with an increase in the arterial hepatic blood flow. The physiological implications of these haemodynamic changes in the long term remain to be investigated.

Esplenectomia e ligadura da veia gástrica esquerda na esquistossomose mansônica: efeitos sobre pressão das varizes do esôfago e indicadores endoscópicos de risco de sangramento por varizes esofagogástricas

BACKGROUND A significant number of patients with schistosomiasis develop the hepatosplenic form, with portal hypertension, in which bleeding caused by rupture of esophagogastric varices emerged as the leading cause of morbidity and mortality. AIM To investigate the effects of splenectomy and ligature of the left gastric vein on risk factors for bleeding of esophagogastric varices in patients with schistosomiasis mansoni, hepatosplenic form, with a history of upper gastrointestinal bleeding. METHODS The main risk factors of bleeding from esophagogastric varices were studied in 34 patients. The following parameters were investigated: 1) esophageal variceal pressure, measured by the endoscopic pneumatic balloon technique; 2) size, fundamental color, extension and red signs of esophageal varices, gastric varices and gastropathy of portal hypertension. The evaluations were performed in the preoperative period, immediate postoperative period (between the sixth and eighth postoperative days) and the sixth month of follow-up. RESULTS The variceal pressure has fallen from 22.3+/-2.6 mmHg before surgery to 16.0+/-3.0 mmHg in the immediate postoperative period (p<0.001), reaching 13.3+/- 2.6 mmHg in the sixth month of follow-up. A significant reduction of the frequency of the parameters associated with a greater risk of hemorrhage was observed between the preoperative period and six-month follow-up, when the proportion of large esophageal varices (p<0.05), varices extending to the upper esophagus (p<0.05), bluish varices (p<0.01), varices with red signs (p<0.01) and gastropathy (p<0.05) decreased. CONCLUSION In patients with hepatosplenic schistosomiasis with a previous history of variceal hemorrhage, splenectomy and gastric vein ligation was effective in reducing the main hemorrhagic risk factors until the sixth month of follow-up, indicating a good way to control the bleeding episodes.BACKGROUND: A significant number of patients with schistosomiasis develop the hepatosplenic form, with portal hypertension, in which bleeding caused by rupture of esophagogastric varices emerged as the leading cause of morbidity and mortality. AIM: To investigate the effects of splenectomy and ligature of the left gastric vein on risk factors for bleeding of esophagogastric varices in patients with schistosomiasis mansoni, hepatosplenic form, with a history of upper gastrointestinal bleeding. METHODS: The main risk factors of bleeding from esophagogastric varices were studied in 34 patients. The following parameters were investigated: 1) esophageal variceal pressure, measured by the endoscopic pneumatic balloon technique; 2) size, fundamental color, extension and red signs of esophageal varices, gastric varices and gastropathy of portal hypertension. The evaluations were performed in the preoperative period, immediate postoperative period (between the sixth and eighth postoperative days) and the sixth month of follow-up. RESULTS: The variceal pressure has fallen from 22.3+/-2.6 mmHg before surgery to 16.0+/-3.0 mmHg in the immediate postoperative period (p<0.001), reaching 13.3+/- 2.6 mmHg in the sixth month of follow-up. A significant reduction of the frequency of the parameters associated with a greater risk of hemorrhage was observed between the preoperative period and six-month follow-up, when the proportion of large esophageal varices (p<0.05), varices extending to the upper esophagus (p<0.05), bluish varices (p<0.01), varices with red signs (p<0.01) and gastropathy (p<0.05) decreased. CONCLUSION: In patients with hepatosplenic schistosomiasis with a previous history of variceal hemorrhage, splenectomy and gastric vein ligation was effective in reducing the main hemorrhagic risk factors until the sixth month of follow-up, indicating a good way to control the bleeding episodes.

Manifestações oculares em pacientes que tiveram desnutrição nos primeiros seis meses de vida

PURPOSE To investigate possible ophthalmologic alterations in patients who had severe malnutrition during the first six months of life. METHODS 182 eyes of 91, 2 to 11-year-old, children who had had severe malnutrition during the first six months of life (study group) were analyzed. As a control group 88 children selected according to similar characteristics of age, gender, demographic and economic conditions were included. RESULTS In the study group, a higher frequency of children with visual acuity from 0.3 to 0.1 and less than 0.1 (11.5% versus 0.7% - p< 0.0001) was observed. There was a higher frequency of astigmatism and myopia in the study group. A higher frequency of astigmatism of one diopter or more in the study group (p< 0.0001) was also observed. The fundoscopic alterations were pale optic nerve (2.2%), increased disc cup (4.4%), increased vascular tortuosity (6.6%), alteration of retina color (13.2%) and retinal pigment epithelium cell atrophy (12.0%). CONCLUSIONS The present data support the concept that early malnutrition interferes in the individuals visual health. Further studies are necessary to establish a more precise cause-effect relationship.

Fetal alcohol spectrum disorders among children in a Brazilian orphanage

BACKGROUND The objective was to investigate the frequency of fetal alcohol spectrum disorders (FASD) and ophthalmologic anomalies in orphanage children in Brazil. METHODS A prospective study was performed on 94 children living in an orphanage in Brazil. The children were examined by a multidisciplinary team consisting of specialists in pediatrics, neurology, psychology, neuropsychiatry, and ophthalmology. RESULTS The main reasons for living in the orphanage, in 61% of the children, were negligence, child abuse, and abandonment. Of all the children studied, 50% had mothers with known alcohol abuse and 47% had one or more diagnoses of neurodevelopmental/behavioral and/or cognitive deficits. General developmental delay was found in 18%, intellectual disability in 3%, cognitive impairment in 27%, attention-deficit/hyperactivity disorder in 14%, and autism in 3%. Altogether 17% had FASD, comprising three children with fetal alcohol syndrome (FAS), six with partial FAS, and seven with alcohol-related neurodevelopmental disorder. 16% had ophthalmological findings such as poor vision, strabismus, and dysmorphology of the optic nerves. Twenty-eight children (30%) were adopted from the orphanage; of these, six had FASD (two FAS, three partial FAS, one alcohol-related neurodevelopmental disorder), five had attention-deficit/hyperactivity disorder, and eight had developmental delay. CONCLUSION Nearly half of the children living in the orphanage had neurodevelopmental disorders and a considerable number showed signs of damage from prenatal alcohol exposure. A broader look at the problem of FASD in Brazil and other South American countries is desirable to document the burden of disease and provide data for targeting prevention efforts.