Register and clinical follow-up of patients with Peutz-Jeghers syndrome in Valencia. / Registro y seguimiento clínico de pacientes con síndrome de Peutz Jeghers en Valencia.

INTRODUCTION AND OBJECTIVES: Peutz-Jeghers syndrome is a rare autosomal dominant inherited disease caused by a germline mutation of the STK11/LKB1 gene, located on chromosome 19p13.3. It is characterized by mucocutaneous hyperpigmentation, hamartomatous polyposis, and predisposition to cancer. The aim of the present study was to identify and register patients with Peutz-Jeghers syndrome, describe the disease, and estimate its prevalence in Valencia (Spain). MATERIALS AND METHODS: A print-out of the clinical histories from 10 hospitals was obtained utilizing the ICD-9 code 759.6 from the Minimum Basic Data Set of Hospital Admissions of the Spanish Ministry of Health and Consumer Affairs. RESULTS: From a total of 405 clinical histories found, 15 (9 males and 6 females) fit the diagnostic criteria of Peutz-Jeghers syndrome. Mean age at diagnosis was 13.8 years and mean age at death was 54.2 years. Four males died, all from cancer. The estimated disease prevalence was 0.4/100,000 inhabitants. All the patients presented with anemia and polyps in the small bowel (80% in the duodenum, 66.7% in the ileum, and 40% in the jejunum), 93.3% underwent urgent surgical intervention and presented with intestinal invagination, and 40% of the patients developed cancer at a mean age of 48.5 years. CONCLUSION: The present study is the first register of patients with Peutz-Jeghers syndrome in Valencia, Spain. The ICD-9 code is nonspecific for rare diseases. The duodenum was the most frequent location for polyps and the majority of cases presented with intestinal invagination, bowel obstruction, and urgent surgical intervention. A large percentage of patients presented with cancer. It would be of interest to review and evaluate the existing surveillance protocols in the Valencian Community.

Reduced retinal nerve fibre layer thickness in children with severe obesity.

BACKGROUND: Some optic nerve diseases are silent and insidious. Recently, reduced thickness of retinal nerve fibre layer (RNFL) has been associated with increasing body mass index in adults. OBJECTIVES: To investigate the association of childhood obesity with RNFL measured by optical coherence tomography imaging. METHODS: Ninety-seven children aged 5-14 years classified according to standard deviation score of body mass index (SDS-BMI) were included. Parameters of metabolic risk, adipocytokines (leptin, adiponectin) and interleukin-6 were analyzed. All subjects underwent a comprehensive ophthalmologic examination with direct ophthalmoscopy. Evaluation of RNFL with optical coherence tomography of the head of the nerve was performed. RESULTS: RNFL thickness on the average and inferior, superior and nasal quadrants were decreased in severely obese children (SDS-BMI > 4) with respect to the other groups. However, no statistically significant association was found between the different groups of children and RNFL thickness in the temporal quadrant. There was a significant inverse correlation of RNFL thickness with adiposity indices (P = 0.016), leptin (P = 0.029) and interleukin-6 (P = 0.030) in overweight and obese children. CONCLUSIONS: These findings suggest that adiposity and obesity-related inflammatory factors may be associated with the loss of retinal ganglion cells in children.

Left ventricular diastolic function and cardiometabolic factors in obese normotensive children.

BACKGROUND AND AIM: Left ventricular (LV) hypertrophy and diastolic function have been found to be associated with obesity and hypertension in adults. However, there are scarce data about the association of obesity itself to cardiac alteration in children. The aim of this study was to detect early changes in LV structure and function in obese children and whether they are associated with the biomarkers of metabolic risk and endothelial activation. METHODS AND RESULTS: A total of 130 children aged 7-16 years (88 obese and 42 normal-weight children) were studied. All children had normal resting blood pressure. Two-dimensional ultrasound with M-mode imaging was performed to assess the LV mass index (LVMi), calculated as LV mass/height(2.7), and the peak diastolic of pulmonary venous flow velocity (PVFD). Tissue Doppler imaging was used to analyze ventricular performance through the ratio of the transmitral peak early filling velocity to the early average diastolic peak myocardial velocity (E/E'). The indicators of metabolic control, inflammation, and endothelial cell activation were evaluated. Compared to the controls, the obese subjects had significantly higher LVMi and E/E' and lower PVFD values, the two latest being found especially in severely obese subjects. In the multivariate analysis, the parameters of diastolic function (E/E' and PVFD) were independently associated with obesity, apolipoprotein A1, soluble vascular cell endothelial molecule-1 (sVCAM-1), and retinol-binding protein 4 (RBP4). CONCLUSION: An echocardiographic evaluation of diastolic function is a useful tool to detect early cardiac changes in obese children. Emergent cardiovascular risk markers such as apolipoprotein A1, RBP4, and sVCAM-1 are associated with the parameters of diastolic function.

Elevated advanced oxidation protein products (AOPPs) indicate metabolic risk in severely obese children.

BACKGROUND AND AIMS: The assessment of oxidative stress may aid in the identification of subsequent metabolic risk in obese children. The objective of this study was to determine whether the plasma level of advanced oxidation protein products, analyzed with a recently proposed modified assay that involves a delipidation step (mAOPPs), was related to metabolic risk factors (MRFs) in severely obese children. METHODS AND RESULTS: The plasma levels of mAOPPs were determined by spectrophotometry in 54 severely obese and 44 healthy children. We also measured lipid peroxidation biomarkers (thiobarbituric acid-reactive substances, malondialdehyde, and 8-isoprotane F(2α)) and sulfhydryl groups, a marker of antioxidant defense. Protein oxidation and lipid peroxidation markers were higher and sulfhydryl levels were lower in obese children compared with controls. Taking metabolic risk into account, obese children were subdivided according to the cutoff point (53.2 µmol/L) obtained for their mAOPPs values from the ROC curve. Anthropometric measures and the existence of hypertension did not differ between groups. The presence of dyslipidemia and insulin resistance was significantly higher in the group with higher mAOPPs levels. The highest levels of mAOPPs were found in the children with ≥3 MRFs. The level of mAOPPs was positively correlated with triglycerides and negatively correlated with high-density lipoprotein cholesterol. There was no correlation of this marker of protein oxidation with biomarkers of lipid peroxidation. CONCLUSION: The determination of mAOPPs in delipidated plasma is an easy way to evaluate protein oxidation. It may be useful in severely obese children for better cardiovascular risk assessment.

New factors of cardiometabolic risk in severely obese children: influence of pubertal status.

The aim of this prospective study was to evaluate the utility of new biochemical markers to assess cardiometabolic risk in severely obese children and adolescents. A total of 107 subjects aged 7 to 14 years, were clinically assessed and anthropometric measures and percentage of fat mass by single frequency bioimpedance analysis were recorded. Of these, 44 were non-overweight and 63 severely obese (body mass index Z-score>2.5) which were stratified by Tanner stages. To estimate the metabolic risk the following variables were considered for analysis: Waist circumference/height>0.5, fasting glucose>100 mg/dL, triglycerides>110 mg/dL, HDL-C<40 mg/dL, and systolic or diastolic blood pressure>95th percentile for age and gender. Fasting insulinemia, apoprotein A1 and B, high-sensitive C-reactive protein, alanine aminotransferase, homocysteine, and folic and uric acids were determined. In severely obese children, metabolic risk was present more frequently in mid puberty. The normalized anthropometric parameters with respect to 50th percentile for age and gender did not differ in the presence of metabolic risk. Insulin resistance was an independent determinant of metabolic risk, adjusted by Tanner stages. Elevated high-sensitive C-reactive protein was noted without any effect of metabolic risk or pubertal stage. Homocysteine, apoprotein B, and alanine aminotransferase values increased with metabolic risk and were not influenced by puberty. Although insulin resistance remains the main factor influencing metabolic risk, biochemical markers as homocysteine, apoprotein B, and alanine aminotransferase, may be useful for identifying severe obese pubertal subjects particularly prone to comorbidities.

[Contiguous gene deletion syndrome in Xp21: an unusual form of presentation]. / Síndrome de deleción de genes contiguos en Xp21: una forma inusual de presentación.

INTRODUCTION: We report a case of an infant where the association of Duchenne's muscular dystrophy (DMD) and pseudohypertriglyceridaemia led to the diagnosis of contiguous gene deletion syndrome in Xp21. CASE REPORT: A 7-month-old male infant who was referred due to psychomotor retardation. The examination revealed pronounced axial hypotonia. Lab findings showed high levels of muscular enzymes with creatine phosphokinase levels of 12,829 IU/L, together with high blood levels of triglycerides. Electromyogram findings were consistent with myopathic compromise. The genetic study for dystrophinopathies revealed the existence of a deletion in the dystrophin gene. Further lab findings identified high glycerol concentrations both in blood and in urine that were compatible with a glycerol kinase deficiency. The genetic study confirmed the existence of a deletion in Xp21 of the genes responsible for DMD, the glycerol kinase deficiency, the congenital adrenal hypoplasia (gene DAX1) and mental retardation (gene IL1RAPL1). CONCLUSIONS: In infants and small children with myopathic compromise, increased levels of creatine phosphokinase and pseudohypertriglyceridaemia it is essential to take into account contiguous gene deletion syndrome in Xp21 to be able to prevent and treat the metabolic complications arising from adrenal hypoplasia.

[Gastric emptying in children with gastroesophageal reflux. Evaluation by real time ultrasonography of the pyloric antrum]. / Vaciamiento gástrico en el niño afecto de reflujo gastroesofágico. Valoración mediante ecografía en tiempo real de la región antro-pilórica.

OBJECTIVE: We have studied gastric emptying using real time ultrasound in 25 healthy children and 25 children with RGE. Our aim was to establish the time and mode of gastric emptying and the volume and the degree of antral dilation in both groups at baseline and after a test meal. We also evaluated the same parameters in the RGE cases after supplying a prokinetic. PATIENTS AND METHODS: The Bolondi technique was used to measure the basal antrum volume and emptying ratio, as well as the mode and final gastric emptying time at different time-points after a solid-liquid test meal. RESULTS: Patients with RGE have a clearly longer gastric emptying time with respect to the healthy subjects in both children less than one year of age (238 +/- 48.4 vs 176.3 +/- 36.7 minute; p = 0.03) and those 1-14 years old (206.3 +/- 48.2 vs 163.3 +/- 48.1 minutes, p = 0.03). An anomalous gastric emptying, similar to a broken line, can be observed in children suffering from RGE. In contrast, a progressive reduction of antrum dilation ration was seen in healthy children and not in patients with RGE. After cisapride, gastric volume goes down at all test times in RGE children. Therefore, a decrease in final gastric emptying time cannot be observed. CONCLUSIONS: Children suffering from RGE show an alteration in gastric emptying with a clearly greater time and an anomalous mode of emptying. The antrum remained dilated for longer periods after ingestion of test food.

[Cholestatic-type hepatitis in childhood]. / Hepatitis de tipo colestásico en la infancia.

OBJECTIVE: The aim of this study was to evaluate the incidence, etiology, clinical evolution and prognosis of cholestatic hepatitis during childhood. PATIENTS AND METHODS: A retrospective study of 145 children hospitalized for acute hepatitis between December 1983 and September 1996 were studied. Cholestatic hepatitis was defined by a direct bilirubin higher than 50% of the total bilirubin. RESULTS: Five cases were identified, which represents 3.45% of all hospitalized hepatitis cases. The average age was 8 years. Cholestatic symptomatology was predominant in all cases with bilirubin values ranging from 10.5 to 32 mg/dl. Cytolysis ranged from moderate to intense. Regarding enzymes indicating cholestasis, the most elevated was 5'nucleotidase, followed by GGT. Quick's index was abnormal in 2 cases, one of which was not corrected by vitamin K. Cholesterol, triglycerides and gamma globulins were slightly increased. In only one case was there a thickening of the wall of the vesicula, which was dilated. Three cases corresponded to hepatitis A virus, one to hepatitis B virus and SMA (smooth muscle autoantibodies) were identified in the fifth. Evolution was favorable in all patients within 8 weeks, except for a girl with subacute hepatocellular insufficiency (SMA positive) where a normal state was achieved 3 months after immunosuppression treatment was started. CONCLUSIONS: 1) Cholestatic hepatitis is an infrequent form of acute hepatitis evolution in childhood and can be promoted by hepatitis virus A or B. 2) It shows a favorable prognosis, except when it comes from a non-viral etiology.

Long-term follow-up of growth in height after successful liver transplantation.

Quantitative assessment of growth in height during the long-term follow-up of children who underwent orthotopic liver transplantation was done to allay concerns related to the progress of the children in terms of normal relationships with peers. Height curves were constructed for 119 children who received transplants at Bicêtre and Cochin Hospitals and were followed for more than 1 year. Poor linear growth was observed during the first 6 months after transplantation, during which time children received corticosteroids daily. The onset of catch-up growth was observed between 6 and 24 months after transplantation, and its magnitude did not differ between male and female patients. Both boys and girls underwent a normal pubertal growth spurt and normal development of secondary sexual characteristics. All adolescent girls had regular menstrual cycles, and one delivered a normal infant 6 years after transplantation. Patients who received transplants before the age of 2 years had poor average growth velocity by the third year after transplantation. Linear growth improved in almost all children and was not affected by the cause of the liver disease that existed before the liver transplantation except that fulminant hepatic failure was associated with poor growth. Long-term improvement of growth in height usually is obtained after liver transplantation in most children with chronic liver diseases. The use of low doses of corticosteroids, administered on an alternate-day basis, contributes to this improvement. Young age of the patient, but not the cause of the chronic liver disease, appears to influence the long-term outcome of linear growth.

Anti-rat liver microsomal and cytosolic antibodies in hepatitis C virus infection.

In order to assess the frequency of autoimmunity markers in hepatitis C virus infection, 229 RIBA 2 HCV positive individuals were tested by ELISA and Immunoblot assay using as antigen rat liver microsomal and cytosolic proteins. Twenty-one out of 229 individuals (9%) showed anti-rat liver microsome antibodies by ELISA, but the titre was low (1:100 to 1:1,600). In Immunoblot, only 5 of these 21 ELISA positive sera recognized also rat liver microsomal proteins (MW between 30 to 64 kDa). Antibodies against rat liver cytosolic proteins were found by ELISA in 14 out of 229 individuals (6%). Three of them showed a reactivity in Immunoblot to 42 kDa or 55 kDA proteins. In conclusion, HCV infection could induce an autoimmune response against rat liver microsomal and cytosolic proteins in a small number of subjects; the titre of antibodies being lower and the pattern of reactivity different in respect to patients with autoimmune hepatitis.

Clinical and immunological heterogeneity of anti-liver-kidney microsome antibody-positive autoimmune hepatitis in children.

A group of children with autoimmune hepatitis is characterized by the presence in their sera of anti-liver-kidney microsome antibody (LKMA) as defined by immunofluorescence. Immunoblot analysis of the sera of 21 such children using rat-liver microsome total proteins as antigen allowed separation into three groups--group 1, whose sera recognized a 50 kDa protein; group 2, whose sera recognized a 66 kDa protein; and group 3, whose sera recognized both proteins. Patients with the anti-66-kDa reactivity more often displayed an acute onset of the disease, less signs of portal hypertension, better sensitivity to immunosuppressive therapy, and less tendency to relapse. They also displayed a lower titer of anti-rat-liver microsome antibody in enzyme-linked immunosorbent assay (ELISA) and a serum reactivity with a rat-liver cytosolic protein. These results (a) indicate that the LKMA-positive autoimmune hepatitis of children is heterogeneous from both clinical and immunological view points, (b) suggest that children with anti-66-kDa reactivity could have a less severe disease than children with the 50-kDa reactivity, and (c) indicate that immunoblot analysis should be added to ELISA and immunofluorescence studies to achieve better characterization of these patients.

[Anti-endomysium antibodies: new serological markers for the diagnosis and follow-up of patients with gluten-sensitive enteropathy. Preliminary study]. / Anticuerpos antiendomisio: un nuevo marcador serológico para el diagnóstico y seguimiento de pacientes afectos de enteropatía sensible al gluten. Estudio preliminar.

The authors value the parameters of diagnostic efficacy in a preliminary study of anti-endomysium antibodies (EmA), in the diagnostic and follow-up of patients with gluten sensitive enteropathy. The study was made with 84 subjects distributed into four groups. Group I consisted of 21 patients with gluten sensitive enteropathy (GSE) who were eating gluten at the time of diagnosis. Group II consisted of 20 patients with gluten sensitive enteropathy with different periods of time of gluten free diet. Group III consisted of 16 subjects with non-evolutive neuropathies and without intestinal disease. This group was considered as controls. Group IV consisted of 27 patients with toddler diarrhoea. The sensitivity, specificity, positive predictive value, negative predictive value and efficiency were 100%.

A new antigen recognized by anti-liver-kidney-microsome antibody (LKMA).

Sera from 23 children with autoimmune chronic active hepatitis and positive for anti-liver-kidney-microsome antibody (LKMA), as defined by immunofluorescence, were analysed by Western blot (WB) and two-dimensional gel electrophoresis using rat liver microsomes as antigen, and by WB and dot-blot analysis with rat liver microsomal subfractions. Western blot analysis showed three patterns of reactivity: 13 sera recognized a 50 kD polypeptide, six sera a 66 kD polypeptide and four sera both of them. Two-dimensional gel electrophoresis, WB, and dot-blot analysis showed the 66 kD antigen to have a pI of 5.4 and to be located in the smooth domain of the endoplasmic reticulum. Western blot analysis using monospecific antisera against human IgG subclasses showed the LKMA directed against the 66 kD antigen to be mainly of the IgG1 subclass. These results indicate that LKMA associated with a subgroup of autoimmune hepatitis of children react with at least two different microsomal antigens in rat liver: (1) the 50 kD polypeptide, recently shown to be a cytochrome P-450 of the IID subfamily, and (2) a new antigen of 66 kD, the location of which suggests it may also be part of the mono-oxygenase complex.

[Therapeutic results in Giardia lamblia infestation]. / Resultados terapéuticos de la infestación por Giardia lamblia.

Therapeutic effects of metronidazole (Flagyl), tinidazole (Tricolam 500) and chlorhydrate of quinacrine in a study of 106 children with symptomatic giardiasis are compared. To evaluate results, cure percentage, efficacy and presence of secondary effects were quantified. Tinidazole was demonstrated most effective drug (96% effective) when compared with quinacrine (83.3% effective) and metronidazole (70.2%) (p less than 0.05). Authors recommend following regime: tinidazole 50-75 mg/kg divided in 2-3 doses, one day; chlorhydrate of quinacrine 6 mg/kg/day divided in 3 doses, five days; metronidazole 15-20 mg/kg/day divided in 3 doses, seven to ten days.

[Course of chronic hepatitis related to B virus in children. Study of serum viral DNA]. / Evolution des hépatites chroniques liées au virus B chez l'enfant. Etude de l'ADN viral sérique.

Nineteen children with chronic hepatitis related to the hepatitis B virus were followed for an average of 6 years. The determination of the hepatitis B virus DNA in the serum allowed us to know the state of viral replication. Thus three groups of patients could be defined: the first in which replication remained active during the total period of follow-up; the second in which the extinction of replication was observed; the third in which replication was inactive from the beginning of the serological follow-up. Symptoms, high levels of aminotransferases and histologically aggressive lesions, sometimes with cirrhosis, were more frequent in the presence of viral DNA. During the decrease of the replication, a clear-cut and time-limited increase of serum-aminotransferase levels was often noted. After the disappearance of hepatitis B virus DNA in the serum, clinical signs could be found only in children with cirrhosis or hepatocellular carcinoma. Four cases of hepatitis with initial aggressive lesions led to persistent chronic hepatitis without viral DNA in the serum. In all but one of the patients who started with an aggressive form, viral DNA disappeared in the serum. This loss occurred later and only in 2 patients of 5 who presented initially with chronic persistent hepatitis. Thus a long period of follow-up in childhood chronic hepatitis related to B virus shows frequent inactivation of viral replication. This evolution seemed to occur earlier when the initial histological lesions were aggressive as if this aggressiveness favored the elimination of the virus and the presence of specific antibodies in the serum.(ABSTRACT TRUNCATED AT 250 WORDS)