Gabriel Hessel

Paracoccidioidomycosis in children: clinical presentation, follow-up and outcome

From February, 1981 to May, 2001, 63 children under 15 y old (ages 2 - 15 y, median = 8 y, mean +/- 1 SD = 8 +/- 3 y) presenting 70 episodes of Paracoccidioidomycosis were admitted. The main clinical manifestations and laboratory features observed upon admission were: lymph node enlargement (87.1%), fever (75.7%), weakness (48.6%), pallor (41.4%), hepatomegaly (40%), splenomegaly (35.7%), anemia (90%), hypergammaglobulinemia (88.5%), eosinophilia (75.5%) and hypoalbuminemia (72.5%). Moderate to severe malnutrition was detected in 35.7% of the episodes (Gomezs criterion). Radiographic and technetium studies showed bone lesions in 20 of the episodes, most of them being multiple lytic lesions, involving both long (70%) and plain bones (30%). First line treatment consisted of an association of sulfametoxazole-trimethoprin, which was used, exclusively, in 50 episodes. Follow-up of hemoglobin levels, number of eosinophils in the peripheral blood, albumin and gammaglobulin serum levels revealed significant sequential improvement one and six months after hospital admission, being quite useful to evaluate treatment effectiveness. Six patients died (9.3%) and four developed sequelae (6.3%). In conclusion, the juvenile and disseminated forms can be observed in about 70% of the episodes of PCM occurring in children younger than 15 y old, most of them presenting with a febrile lymphoproliferative syndrome associated to anemia, eosinophilia and hypergammaglobulinemia.

Fibrose cística em um centro de referência no Brasil: características clínicas e laboratoriais de 104 pacientes e sua associação com o genótipo e a gravidade da doença

OBJECTIVE To identify the clinical, laboratory and radiographic characteristics of the cystic fibrosis patients under care at Universidade Estadual de Campinas (UNICAMP) in the last decade of the twentieth century, and to investigate the association of these characteristics with genotype and severity of the disease as measured by the Shwachman score. METHODS Descriptive, retrospective and cross-sectional study of the patients assisted at UNICAMP hospitals Cystic Fibrosis Clinic from July 1990 to July 2000. RESULTS One hundred and four patients were studied; 53.8% male; 93.3% Caucasian; 89.4% presented with respiratory symptoms; 59.6% presented with digestive symptoms; 5.8% had meconium ileus; 4.8% had diabetes. The mean age at onset of symptoms was 3 months, and the mean age at diagnosis was 2 years and 4 months. At diagnosis, 69.9 and 56.6% of the patients had weight and height below 10th percentile, respectively; in 10.6%, sweat chloride was < 60 mEq/l. Staphylococcus aureus was found in 80.2%, Pseudomonas aeruginosa in 76%, and Burkholderia cepacia in 5.2%. DeltaF508 homozygosis was observed in 18.75%, whereas 62.50% of the patients were DeltaF508 heterozygous. A moderate/severe Shwachman score was found in 15.7%. Eighteen patients died in that period (17.3%). The mean age at death was 7 years and 8 months; median survival after diagnosis was 18 years and 4 months. Patients who have at least one DeltaF508 mutation have more frequent alterations in fecal fat levels when compared to patients who do not have this mutation (p < 0.05). There were no differences in any parameter between DeltaF508 homozygous and heterozygous patients. CONCLUSIONS The clinical and laboratory characteristics of the 104 patients studied were similar to the characteristics described for patients in other countries. Exceptions are the higher age at diagnosis and lower survival. Our results support the recommendation for early diagnosis and the need for more treatment opportunities in the population of cystic fibrosis patients.OBJECTIVE: To identify the clinical, laboratory and radiographic characteristics of the cystic fibrosis patients under care at Universidade Estadual de Campinas (UNICAMP) in the last decade of the twentieth century, and to investigate the association of these characteristics with genotype and severity of the disease as measured by the Shwachman score. METHODS: Descriptive, retrospective and cross-sectional study of the patients assisted at UNICAMP hospitals Cystic Fibrosis Clinic from July 1990 to July 2000. RESULTS: One hundred and four patients were studied; 53.8% male; 93.3% Caucasian; 89.4% presented with respiratory symptoms; 59.6% presented with digestive symptoms; 5.8% had meconium ileus ; 4.8% had diabetes. The mean age at onset of symptoms was 3 months, and the mean age at diagnosis was 2 years and 4 months. At diagnosis, 69.9 and 56.6% of the patients had weight and height below 10th percentile, respectively; in 10.6%, sweat chloride was < 60 mEq/l. Staphylococcus aureus was found in 80.2%, Pseudomonas aeruginosa in 76.0%, and Burkholderia cepacia in 5.2%. DF508 homozygosis was observed in 18.75%, whereas 62.50% of the patients were DF508 heterozygous. A moderate/severe Shwachman score was found in 15.7%. Eighteen patients died in that period (17.3%). The mean age at death was 7 years and 8 months; median survival after diagnosis was 18 years and 4 months. Patients who have at least one DF508 mutation have more frequent alterations in fecal fat levels when compared to patients who do not have this mutation (p < 0.05). There were no differences in any parameter between DF508 homozygous and heterozygous patients. CONCLUSIONS: The clinical and laboratory characteristics of the 104 patients studied were similar to the characteristics described for patients in other countries. Exceptions are the higher age at diagnosis and lower survival. Our results support the recommendation for early diagnosis and the need for more treatment opportunities in the population of cystic fibrosis patients.

INFECTION BY CYTOMEGALOVIRUS IN PATIENTS WITH NEONATAL CHOLESTASIS

BACKGROUND Neonatal cholestasis syndrome with an intra or extrahepatic origin has been associated to viral infections. The participation of the cytomegalovirus in the etiopathogenesis of neonatal hepatitis has been already known for some time, but only recently there have been indications that this virus may be one of the possible etiological factors for extrahepatic biliary atresia. AIMS To assess the prevalence of infection by cytomegalovirus in patients with intrahepatic cholestasis and extrahepatic cholestasis. To compare the clinical characteristics of the intrahepatic cholestasis and extrahepatic cholestasis groups with the cytomegalovirus serological results. Patients and Methods - This study consisted of 76 patients with neonatal cholestasis who were admitted between January 1980 and January 1999 when they underwent a cytomegalovirus serologic study using the ELISA method. A case note was kept on each patient with the following data: age of patient at admission, serologic result for cytomegalovirus, history of maternal infection, prematurity, fetal distress, birth weight, ponderal gain, choluria and fecal acholia. The final anatomic diagnosis of cholestasis was based on the results of an abdominal ultrasonography, a liver biopsy and its evolution. The patients were then divided into two groups: group I - intrahepatic cholestasis and group II - extrahepatic cholestasis. Each of these groups were then divided into two subgroups: subgroup A - positive serology (IgM) for cytomegalovirus and subgroup B - negative serology (IgM) for cytomegalovirus. RESULTS The frequency of positive serology (IgM) for cytomegalovirus was 29.4% in children with intrahepatic cholestasis and 28.5% in children with extrahepatic cholestasis. In comparison with group IIB, group IIA presented a higher rate of maternal infection history. The patients in group IIA demonstrated a delayed access to the service in comparison with group IA. The groups did not demonstrate any significant differences regarding the onset age of jaundice, choluria and fecal acholia, birth weight and ponderal gain. CONCLUSIONS The positive (IgM) seroprevalence for cytomegalovirus in children with intrahepatic cholestasis and extrahepatic cholestasis is high. The history of maternal infection was more common in extrahepatic cholestasis patients with positive serology for cytomegalovirus. There was a delay in the referral of these patients which resulted in a late diagnosis and surgical treatment.

High frequency of Human Cytomegalovirus DNA in the Liver of Infants with Extrahepatic Neonatal Cholestasis

BackgroundBiliary atresia (BA) is the most severe hepatic disorder in newborns and its etiopathogenesis remains unknown. Viral involvement has been proposed, including the human cytomegalovirus (HCMV). The aims of the study were to use the polymerase chain reaction (PCR) to screen the liver tissue of infants with extrahepatic cholestasis for HCMV and to correlate the results with serological antibodies against HCMV and histological findings.MethodsA retrospective study in a tertiary care setting included 35 patients (31 BA, 1 BA associated with a choledochal cyst, 2 congenital stenosis of the distal common bile duct and 1 hepatic cyst). HCMV serology was determined by ELISA. Liver and porta hepatis were examined histologically. Liver samples from infants and a control group were screened for HCMV DNA.ResultsTwelve patients had HCMV negative serology, 9 were positive for IgG antibodies and 14 were positive for IgG and IgM. Nine liver and seven porta hepatis samples were positive for HCMV DNA but none of the control group were positive (general frequency of positivity was 34.3% – 12/35). There was no correlation between HCMV positivity by PCR and the histological findings. The accuracy of serology for detecting HCMV antibodies was low.ConclusionThese results indicate an elevated frequency of HCMV in pediatric patients with extrahepatic neonatal cholestasis. They also show the low accuracy of serological tests for detecting active HCMV infection and the lack of correlation between HCMV positivity by PCR and the histopathological changes.

Nutritional status of patients with biliary atresia and autoimmune hepatitis related to serum levels of vitamins A, D and E

CONTEXT Chronic liver disease may induce to malabsorption of lipids and fat-soluble vitamins, leading to injury of nutritional status. OBJECTIVES To evaluate the nutritional status of pediatric-age patients with autoimmune hepatitis and biliary atresia related to serum levels of vitamins A, D and E and the disease severity. METHODS This controlled transverse study, evaluated the patients with autoimmune hepatitis and biliary atresia and a reference group paired by sex and age. The patients underwent anthropometric evaluation, alimentary inquiry and determination of serum levels of vitamins A, D and E by high performance liquid chromatography. The Mann-Whitney test, Spearman correlation coefficients and variance analysis (ANOVA) were utilized for data treatment, regarding significant difference if P<0.05. RESULTS The highest nutritional deficit was observed in patients with biliary atresia, mainly with cholestasis. The serum levels of vitamins A and E for the reference group changed as a function of age. The serum levels of vitamins A, D and E were higher in reference group than in patients with biliary atresia and autoimmune hepatitis together or separately. There were not difference in the serum levels of vitamins A, D and E between biliary atresia groups with cholestasis and without cholestasis. It was verified correlation between weight/age, triceps skinfold thickness, subscapular skinfold thickness, midarm circumference, midarm fat area values and vitamin A serum levels, as well as between all anthropometric indicators and vitamin E in patients with autoimmune hepatitis and biliary atresia. CONCLUSION The patients with biliary atresia and cholestasis presented the highest nutritional injury. The patients with biliary atresia and autoimmune hepatitis presented lower serum levels of vitamins A, D and E that in control group. There is a directly proportional correlation between vitamin serum levels, mainly vitamin E, and all anthropometric variables of biliary atresia and autoimmune hepatitis groups.

Associação entre os polimorfismos dos genes MBL2, TGF-β1 e CD14 com a gravidade da doença pulmonar na fibrose cística

Objective: To identify associations between genetic polymorphisms (in the MBL2, TGF-β1 and CD14 genes) and the severity of the lung disease in patients with cystic fibrosis (CF), as well as between the presence of ΔF508 alleles and lung disease severity in such patients. Methods: This was a cross-sectional cohort study, based on clinical and laboratory data, involving 105 patients with CF treated at a university hospital in the 2005-2006 period. We included 202 healthy blood donors as controls for the determination of TGF-β1 and CD14 gene polymorphisms. Polymorphisms in the MBL2 and TGF-β1 genes at codon 10, position +869, were genotyped using the allelespecific PCR technique. The C-159T polymorphism in the CD14 gene was genotyped using PCR and enzymatic digestion. Results: Of the 105 CF patients evaluated, 67 presented with severe lung disease according to the Shwachman score. The MBL2 gene polymorphisms were not associated with disease severity in the CF patients. Analysis of the T869C polymorphism in the TGF-β1 gene showed an association only between TC heterozygotes and mild pulmonary disease. Although patients presenting the TT genotype of the C159T polymorphism in the CD14 gene predominated, there was no significant difference regarding lung disease severity. Conclusions: There was an association between the TC genotype of the T869C polymorphism (TGF-β1) and mild pulmonary disease in CF patients. In the CD14 gene, the TT genotype seems to be a risk factor for pulmonary disease but is not a modulator of severity. We found no association between being a ΔF508 homozygote and presenting severe lung disease.

Clinical and biochemical features of autoimmune hepatitis in 36 pediatric patients

BACKGROUND Few studies on autoimmune hepatitis have enrolled non-Caucasian groups. AIMS To evaluate Brazilian children with type 1 and 2 autoimmune hepatitis regarding outcome and clinical and biochemical parameters. PATIENTS AND METHODS Thirty-six patients were submitted to a protocol that evaluated the clinical history, physical and biochemical data, and the course of the disease. Twenty-four children had type 1 autoimmune hepatitis, seven had type 2 and five had unclassified autoimmune hepatitis. Most patients were females (77%), with a median age at diagnosis of 11 years, and the median duration of symptoms was 5.5 and 8 months for types 1 and 2, respectively. Jaundice and choluria were the most common clinical manifestations. RESULTS Treatment with azathioprine and prednisone was successful in patients with type 1 and 2 autoimmune hepatitis. AST and ALT decreased after 4 to 8 weeks of treatment compared to pretreatment levels in type 1 autoimmune hepatitis. Increased GGT values returned to pretreatment levels after 1 year in the two types. Three patients died and three other patients underwent liver transplantation. CONCLUSIONS Non-Caucasian children had a similar disease when compared to Caucasian ones with autoimmune hepatitis. Increased levels of GGT during the first year of treatment should not be the only parameter for the indication of cholangiopathy.

Growth assessment in children with extra-hepatic portal vein obstruction and portal hypertension

BACKGROUND Several studies carried out to examine the growth of children with extra-hepatic portal vein obstruction and portal hypertension have reported a variety of findings. AIM To assess anthropometric indices in children with portal hypertension due to extra-hepatic portal vein obstruction and who were treated by endoscopic variceal sclerotherapy. METHODS Anthropometric data were obtained retrospectively from the medical records of 24 patients who had been followed for 3.8 +/- 2.5 years at the Pediatric Gastroenterology Outpatient Clinic of the University Hospital, Campinas, SP, Brazil. The mean Z scores of weight for age, height for age and body mass index at diagnosis and at the last consultation were compared to reference data of the National Center for Health Statistics. The two recordings were compared to assess the long-term effect of the condition. RESULTS The mean Z scores at diagnosis and at the last follow-up visit were all within normal ranges when compared to the reference population, with the following respective values: weight for age, 0.042 +/- 1.09 and 0.132 +/- 1.29; height for age, 0.200 +/- 1.04 and 0.466 +/- 1.24, and body mass index, -0.223 +/- 0.98 and -0.198 +/- 0.98. In addition, there were no significant differences between the Z score values obtained in the two recordings. CONCLUSION Portal hypertension due to extra-hepatic portal vein obstruction was not associated with growth impairment in the group of children studied.

Metabolic syndrome and insulin resistance in obese adolescents

Objetivo: Verificar a prevalencia da sindrome metabolica e da resistencia a insulina em adolescentes obesos e sua relacao com diferentes indicadores de composicao corporal.Metodos: Estudo transversal com 79 adolescentes de dez a 18 anos. Os indicadores de composicao corporal foram: indice de massa corporea (IMC), porcentagem de gordura corporal, circunferencia abdominal e gordura subcutânea. A sindrome metabolica foi diagnosticada segundo os criterios de Cook et al. A resistencia a insulina foi determinada pelo indice de Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) para valores acima de 3,16. Utilizou-se a analise de curvas ROC para avaliar o IMC e a circunferencia abdominal, identificando-se os individuos com resistencia a insulina e sindrome metabolica. O ponto de corte correspondeu ao percentual acima do valor de referencia para o diagnostico de obesidade.Resultados: A sindrome metabolica foi diagnosticada em 45,5% dos pacientes e a resistencia a insulina, em 29,1%. A resistencia a insulina apresentou associacao com o HDL-colesterol (p=0,032) e com a sindrome metabolica (p=0,006). Todos os indicadores de composicao corporal avaliados apresentaram correlacao com a resistencia a insulina (p<0,01). Na avaliacao dos pontos de corte, os valores de 23,5 e 36,3% acima do valor de referencia do IMC permitiram identificar a resistencia a insulina e a sindrome metabolica. O melhor ponto de corte da circunferencia abdominal para identificar a resistencia a insulina foi de 40%.Conclusoes: Todos os indicadores de composicao corporal, o HDL-colesterol e a sindrome metabolica apresentaram correlacao com a resistencia a insulina. O IMC mostrou-se o indicador antropometrico mais eficaz para identificar a resistencia a insulina.Objective: To verify the prevalence of metabolic syndrome and insulin resistance in obese adolescents and its relationship with different body composition indicators. Methods: A cross-sectional study comprising 79 adolescents aged ten to 18 years old. The assessed body composition indicators were: body mass index (BMI), body fat percentage, abdominal circumference, and subcutaneous fat. The metabolic syndrome was diagnosed according to the criteria proposed by Cook et al. The insulin resistance was determined by the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) index for values above 3.16. The analysis of ROC curves was used to assess the BMI and the abdominal circumference, aiming to identify the subjects with metabolic syndrome and insulin resistance. The cutoff point corresponded to the percentage above the reference value used to diagnose obesity. Results: The metabolic syndrome was diagnosed in 45.5% of the patients and insulin resistance, in 29.1%. Insulin resistance showed association with HDL-cholesterol (p=0.032) and with metabolic syndrome (p=0.006). All body composition indicators were correlated with insulin resistance (p<0.01). In relation to the cutoff point evaluation, the values of 23.5 and 36.3% above the BMI reference point allowed the identification of insulin resistance and metabolic syndrome. The best cutoff point for abdominal circumference to identify insulin resistance was 40%. Conclusions: All body composition indicators, HDL-cholesterol and metabolic syndrome showed correlation with insulin resistance. The BMI was the most effective anthropometric indicator to identify insulin resistance.

Volumetric capnography as a tool to detect early peripheric lung obstruction in cystic fibrosis patients

OBJECTIVE To compare spirometry and volumetric capnography (VCap) to determine if the capnographic values add more information about early lung disease in cystic fibrosis (CF) patients. METHODS This was a cross-sectional study involving CF patients: Group I (42 patients, 6-12 years of age); and Group II (22 patients, 13-20 years of age). The corresponding control groups were comprised of 30 and 50 healthy subjects, respectively. Forced vital capacity (FVC), forced expiratory volume in one second (FEV(1)), and the FEV(1)/FVC ratio was determined by spirometry. Using VCap, we measured peripheral oxygen saturation (SpO(2)), respiratory rate (RR), inspiratory time (IT), expiratory time (ET), and the phase III slope normalized by expiratory volume (phase III slope/Ve). RESULTS In comparison with control groups, all CF patients presented higher phase III slope/Ve values (p < 0.001) independent of the pulmonary disease stage. The phase III slope/Ve was significantly higher in the 24 patients who presented normal spirometry results (p = 0.018). The Group II patients showed lower FVC, FEV(1), FEV(1)/FVC (p < 0.05), and also lower SpO(2) values (p < 0.001) when compared with Group I patients. In comparison with Control Group II, the Group II patients presented higher RR (p < 0.001), and lower IT and ET values (p < 0.001). CONCLUSIONS Compared to the controls, all studied CF patients showed an increase in phase III slope/Ve values. VCap identified the heterogeneity of the ventilation distribution in the peripheral airways of CF patients who presented normal spirometry.