Growth and pubertal disorders in neurofibromatosis type 1.

The first textbook of Pediatric Endocrinology in the early 1950s reported an association of neurofibromatosis type 1 (NF1) and precocious puberty (PP) and/or short stature. Recent studies have indicated that children with NF1 grow normally until puberty; thereafter height velocity and relative height (SDS or percentiles) decreases with respect to healthy peers, reaching a mean adult height close to the 25th percentile for the general population. Moreover, the percentage of patients with true short stature (<3rd percentile) increases from childhood (5%) to late puberty (20-30% in literature, 18% in our study), and final height is significantly below the genetic target and predicted adult height calculated just before or at the beginning of puberty. Finally, among the shortest patients (<10th percentile) there is a high incidence of severe complications, such as CNS tumors, huge plexiform neurofibromas and severe scoliosis. Precocious puberty is a frequent complication of NF1, and occurs mainly in association with optic pathway tumors (OPT); however, occasionally it has been reported in the absence of optic gliomas, probably with a similar incidence as in the general population. GnRH agonist therapy must be decided individually as in some patients further growth could be normal and/or treatment would not improve final height. In the presence of early pubertal signs, an OPT must be ruled out. In addition to PP, delayed puberty has been frequently reported in NF1. In a study of 123 girls with NF1, we found that the mean age at menarche (13.0 +/- 1.9 yr) was later than in their mothers (12.7 +/- 1.4 yr) and in the general population (12.4 +/- 1.2 yr; p <0.05), with a very high incidence of delayed menarche (>2 SD): 16% vs 6.8% (mothers) vs 3.4% (controls) (p <0.01). In conclusion, growth and puberty present unusual patterns in NF1, often with true pathological findings increasing medical and psychological problems.

Hepatitis C virus RNA quantitation in hepatic veins and peripheral blood in patients with liver cirrhosis: evidence for low level intrahepatic hepatitis C virus replication in advanced liver disease.

BACKGROUND: Very few data exist concerning the level of hepatitis C virus replication within the cirrhotic liver and its relationship to disease severity and progression. AIMS: To quantitate hepatitis C virus RNA in hepatic vein blood and peripheral blood in patients with cirrhosis, to evaluate the correlation of hepatitis C virus levels in paired blood samples, and to compare the results with clinical features. PATIENTS: A series of 25 patients with hepatitis C virus-related liver cirrhosis undergoing hepatic vein catheterization were studied: 11 belonged to Child Pugh class A, 8 to class B and 6 to class C. RESULTS: Hepatitis C virus RNA levels did not differ between hepatic vein blood and peripheral blood (p = 0.26), despite a trend towards higher peripheral hepatitis C virus RNA levels. Hepatitis C virus RNA levels did not differ between patients with genotype 1b and non-1b either in hepatic veins or peripheral blood. Hepatitis C virus loads varied according to the severity of cirrhosis. The patients with more severe liver disease had significantly lower RNA titres than those with less advanced cirrhosis, both in hepatic veins (p = 0.002) and peripheral blood (p = 0.004). No differences in hepatitis C virus load were observed between patients in Child Pugh classes B and C. CONCLUSIONS: The present data show that in patients with cirrhosis hepatitis C virus RNA concentrations do not differ between hepatic blood and peripheral blood and, furthermore, confirm that hepatitis C virus replication is reduced in patients with advanced cirrhosis, compared with patients with less severe liver disease. These findings might indicate that patients with liver cirrhosis maintain an efficient intrahepatic hepatitis C virus replication even in end-stage disease, although hepatitis C virus viraemia decreases according to the severity of liver disease.

Neurofibromatosis type 1 and precocious puberty.

Since neurofibromatosis type 1 (NF1) is a well known cause of precocious puberty (PP), we reviewed 412 NF1 pediatric patients to evaluate the prevalence of PP, the association with optic pathway tumors (OPT), and other clinical, auxological and hormonal data. Thirty-one of 412 patients had OPT (7.5%), 10/412 PP (2.4%), and in seven of these PP was associated with OPT (7/31, 22.6%). OPT in patients with PP involved the chiasm in four patients, and the optic nerves alone in three patients. The age at the onset of puberty (or better at diagnosis) ranged from 5.2 to 7.5 yr in girls (n=6) and from 7.9 to 8.9 yr in boys (n=4). LHRH agonist therapy was used in only three children because in the others the predicted height at diagnosis was good, treatment was refused or the patients were referred to us too late. The three treated patients attained a final height within the familial range. In the untreated patients the progression of puberty was not too rapid and final height was slightly below the genetic target in four patients; however, three patients had a final height markedly below the familial range. In conclusion, the prevalence of PP is increased in children with NF1, and frequently but not exclusively is associated with OPT. Moreover, sexual precocity does not seem to be necessarily bound to chiasmatic OPT. Treatment seems to be useful in the children with younger age at the onset of puberty or with a progressive decline in predicted final height.

[Care recommendations for type 1 neurofibromatosis]. / Raccomandazioni assistenziali per la neurofibromatosi tipo 1.

Neurofibromatosis type 1 (NF1) is a progressive, multisystem disorder affecting about 1:3000 individuals. About one third of patients show serious complications and about one half are mildly affected. Since the original National Institutes of Health Consensus Conference in 1987, that established the clinical criteria for the diagnosis of NF1, there has been significant progress toward a more complete understanding of the molecular bases for NF1, and our knowledge of the natural history and management of the NF1 has significantly improved. Despite these advances, the diagnosis of NF1 is still based largely on clinical criteria and no individual prognostic evaluation or definitive medical therapy are available. The recommendations for the care of NF1 patients and their families are constantly changing: according to the new guidelines, the mainstay of management is anticipatory guidance and surveillance for treatable complications; surveillance usually includes annual follow-up visits, unless symptoms call for more frequent visits or more accurate diagnostic evaluation.

[Evaluation and impact on incidence of admission to the neonatal care unit in cases of jaundice after early discharge form the nursery]. / Valutazioni ed impatto sull'incidenza dei ricoveri in Patologia Neonatale dell'ittero dopo dimissione precoce dalla Nursery.

UNLABELLED: We have evaluated the entity of admissions to the Neonatal Care Unit (NCU) for jaundice in the period 1996-2000 of babies early discharged from the Nursery (36-48 hours for spontaneous deliveries and 72-96 hours for cesarean section). We have found an increasing trend of admissions for jaundice (R2 = 0.76), proportional to the increasing practice of early discharge and the early discharge also for infants 34-37 weeks' gestation. The admissions for jaundice from home have increased about 8 times from 1996 to 2000, respectively from 8 to 65 cases. The mean value of maximum total bilirubinemia at admission was 20.5 +/- 2.7 mg/dl. None of the infants underwent exchange transfusion. The most part of the jaundices (69/123) were idiopathic in term infants, followed by those in preterm babies (24/123) and by those in ABO incompatibility without hemolytic disease (15/123). Mean age at admission of the total population was 6.5 +/- 3.0 days, and 9 newborns had signs of dehydration at admission, with weight loss between 11 and 13.8% from birth. Also the admissions for jaundice of extracomunitary babies have resulted increased and they had a longer hospitalization than the rest of the population (p = 0.02). CONCLUSIONS: Early discharge from the Nursery has determined an increase of admissions to NCU for jaundice. New criteria have to be considered to select more carefully the infants that can benefit of this practice.

[Endoscopic and histologic findings of gastric mucosa and Helicobacter pylori prevalence in patients suffering from chronic liver disease]. / Quadro endoscopico ed istologico della mucosa gastrica e prevalenza dell'Helicobacter pylori in pazienti con epatopatia cronica.

In this research we evaluated the prevalence of Hp in the gastric mucosa in patients suffering for chronic liver disease, either chronic hepatitis or liver cirrhosis. Sixty-three patients 27 with chronic hepatitis and 36 with liver cirrhosis, were examined by EGDS; of them we evaluated: endoscopic findings of stomach and duodenum, histology of gastric mucosa (antrum and corpus-fundus), presence of Hp in the histologic samples. We compared the positivity for Hp with the following parameters: presence of esophageal varices, macroscopic aspect of the gastric and duodenal mucosa, presence of hystological findings of gastritis, gastritis's activity, grading of the hepatic damage. In the our research we didn't point out greater prevalence of the Hp in the gastric mucosa with respect to hepatic damage, esophageal varices or macroscopic signs of gastric pathology. The Hp is significantly associated with histologic evidence of gastritis and also with the grade of gastritis's activity. The data of the present work don't suggest any correlation within the pathologic changes of the gastric mucosa caused from the liver cirrhosis and the presence or the growth of Hp.