Effectiveness and safety of ciclosporin as therapy for autoimmune diseases of the liver in children and adolescents.

BACKGROUND: Conventional treatment for autoimmune hepatitis results in a significant percentage of failures and several, poorly tolerated, side-effects. Therapy for autoimmune cholangitis and giant cell hepatitis associated with autoimmune haemolysis is poorly documented. Ciclosporin is a promising treatment for all of these diseases. METHODS: We reviewed the records of 12 patients treated in our unit between 1987 and 2001. Eight had autoimmune hepatitis, two had autoimmune cholangitis and two had giant cell hepatitis. Indications for ciclosporin were treatment failure (four patients) and contraindications to/refusal of steroids (eight patients). Ciclosporin was administered in five untreated cases and in seven patients during relapse. The mean duration of ciclosporin administration was 35.6 months (8-89 months). The median follow-up was 6.5 years (1.5-15 years). RESULTS: All patients achieved complete remission in a median period of 4.5 weeks (2-12 weeks). No treatment withdrawal due to side-effects occurred. Three patients required a combination of ciclosporin with conventional treatment due to severe liver function impairment. Tolerance to ciclosporin was excellent. A 20% transient elevation of serum creatinine occurred in one case, gingival hypertrophy in two and moderate hypertrichosis in two. CONCLUSIONS: Ciclosporin may be considered as a safe treatment for all autoimmune liver diseases and as an effective alternative for front-line therapy.

Muscle thickness in infants hypertrophic pyloric stenosis.

Hypertrophic pyloric stenosis (IHPS) is the most common abdominal abnormality requiring surgery in infants. It occurs due to the hypertrophic and hyperplasia of the muscular layers of the pyloric. The usual age of clinical presentation is about three weeks of life. The most important symptom is non bilious emesis, intermittent or after each feeding. From march 1996 to June 2001, 21 infants, 20 males and 1 female, were subjected to ultrasonographic, radiographic exams and after diagnosis to the pyloromyotomy extramucosa. Ultrasonography was the study of choice used to identify hypertrophic pyloric stenosis; the markers to analyse were the length and the overall diameter of the pyloric canal and the muscle thickness of the wall. The results showed that a length of the pyloric canal 20 +/- 6 mm, a diameter 13.6 +/- 2.5 mm and a muscle thickness 4.1 +/- 1 mm are diagnostics for hypertrophic pyloric stenosis.

Cholestasis as a presenting feature of acute Epstein-Barr virus infection.

Biochemical evidence of hepatic involvement in Epstein-Barr virus disease is common but clinical features of cholestasis are rare in children. We present three children with cholestasis as a presenting feature of Epstein-Barr virus disease.

Gluten-dependent diabetes-related and thyroid-related autoantibodies in patients with celiac disease.

Patients with celiac disease are at high risk of having autoimmune disorders. Moreover, untreated patients with celiac disease have been found to have a higher than expected prevalence of organ-specific autoantibodies. In a prospective study of 90 patients with celiac disease, we found that the prevalence of diabetes and thyroid-related serum antibodies was 11.1% and 14.4%, respectively. Like antiendomysium autoantibodies, these organ-specific antibodies seem to be gluten-dependent and tend to disappear during a gluten-free diet.

Platelet serotonin transporter in coeliac disease.

We investigated a peripheral serotonergic marker, i.e. platelet tritiated imipramine (3H-IMI) binding sites, which are part of the 5-HT transporter complex similar to that present in the brain, in 20 patients affected by coeliac disease (CD), as compared with 20 healthy controls. Platelet membranes and 3H-IMI binding were carried out according to a standardized protocol. The results showed that coeliac patients had significantly lower 3H-IMI binding sites than controls. This finding would suggest the presence of a dysfunction at the level of the 5-HT transporter that might underline the psychic disturbances frequently observed in coeliac patients.

Effect of celiac disease and gluten-free diet on growth hormone-binding protein, insulin-like growth factor-I, and insulin-like growth factor-binding proteins.

Failure to thrive is common in children with celiac disease. As alterations in the growth hormone-insulin-like growth factor I (GH-IGF-I) growth axis have been reported in these patients, we studied the behavior of growth hormone-binding proteins (GH-BPs I and II), IGF-I and its binding proteins in 14 children with celiac disease, either before or after a 6-month gluten-free diet. GH-BP II levels were significantly lower in patients during the active phase of the disease than after the diet or in comparison with control subjects, appropriate for age and sex. There was no difference in the GH-BP-I levels of patients and controls, nor did they change after the diet. Blood levels of IGF-I and IGFBP-3 were reduced before the diet in all patients while ligand blotting showed that IGFBP-2 and 1 were increased. All of these parameters normalized after the gluten-free diet. IGFBP-4 was not greatly influenced by the disease. Furthermore, we found a significant, positive correlation between GH-BP II and IGF-I or IGFBP-3 levels. The height standard deviation scores and body mass indices of the patients improved significantly after the diet. The body mass index significantly and positively correlated with GH-BP II, IGF-I or IGFBP-3 levels. In conclusion, our data show that celiac children had multiple alterations in the growth axis during the active phase of the disease which disappeared during the gluten-free diet.

[Sequelae of bacterial meningitis in childhood: a study of hearing impairment]. / Sequele della meningite batterica in età pediatrica: studio dell'interessamento audiologico.

Bacterial meningitis is an infection of the central nervous system involving quite a number of neurological sequelae the most common of which is hearing impairment. To assess the incidence of audiological deficit the authors evaluated retrospectively 20 patients, between 4 months and 11 years of age, observed at the Pediatric Clinic at the University of Pisa between 1988 and 1993. A clinical-neurological examination and a complete auditory assessment (using BAEPs and impedence audiometry) has been performed in every patient between 1 and 18 months after they left hospital. 4 children had persisting neurological sequelae, 3 patients developed sensorineural hearing loss and one child visual impairment and seizures. Haemophilus Influenzae was responsible for 2 cases of sequelae and Streptococcus Pneumoniae for the other 2 cases. The number of days of illness before hospitalization and the institution of an antibacterial treatment, persistence of fever and deviation from the normal level of consciousness and persistence of neck rigidity were not correlated with the presence of sequelae. No correlation has been found between sensorineural hearing loss and the kind of antibacterial therapy. It's advisable that every child, following bacterial meningitis, should undergo a complete and repeated audiological assessment to detect any lesser impairments and/or unilateral losses that may damage the development of speech and language in any way.

[Peutz-Jeghers syndrome]. / La sindrome di Peutz-Jeghers.

An observation of Peutz-Jeghers syndrome, in a 13 year old girl, provides the Authors with the opportunity of reviewing the clinical features, the natural history and the complications of the disease, mainly the malignancies. In recent reviews the occurrence of cancer was further on investigated: gastrointestinal and non gastrointestinal tumors occurred in 22-48% of the patients examined. The surveillance protocols of the subjects at risk and genetic counseling are discussed.

[Intestinal intussusception in children]. / Invaginazione intestinale nel bambino.

Enteric intussusception is one f the most frequent causes of acute abdomen in early childhood, with an incidence of 1.3-2/1000 children born and higher frequency from the third to the twelfth month. Primary intussusception is related to predisponsing factors such as peristalsis disorders or Peyer's patch hypertrophy induced by viral infection. Secondary intussusception is due to organic injury in the intestinal wall. The most involved sites are the terminal ileum and the ileocecum, the most frequent type is ileocolic intussusception. Many clinical forms exist, including acute enteric intussusception with its pathognomonic triad intermittent abdominal pain, emesis and rectal bleeding and the atypical form with a neurological presentation, where sopor, myosis and muscular atonicity are dominating, Intussusception can also present in a subacute or chronic form with a slow and apsecific onset. In a retrospective investigation we examined 30 cases of intussusception in children hospitalized at the Pediatric Clinic of Pisa from the 1960s up to today. Our patients (16 males and 14 females) were aged between one month and two years. Clinical presentations resulted in; typical forms (60%), atypical forms (16%), subacute forms 13%) and recurrent forms (10%). Clinical suspicion was confirmed either by the presence of blood observed during rectal exploration, which is a pathognomonic sign, or by the opaque enema which led to recovery by means of hydrostatic reduction in 40% of the cases. The remaining patients (60%) underwent surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

[Celiac disease and cystic fibrosis: casual association?]. / Malattia celiaca e fibrosi cistica: associazione casuale?

The authors describe a case of association cystic fibrosis coeliac disease, which they have observed. The frequency of this association in the general population is of 1:2,000,000. M.A. presents little growth in terms of height and weight and intestinal alterations (an abundance of fatty and mucous stool). The initial diagnosis was that of coeliac disease. After two months of diet without gluten one observed an increase in weight, but o result for the intestinal disturbances. The positive result revealed from the sweat-test and the study of genomic mutation (delta F508) showed the diagnosis of cystic fibrosis associated with coeliac disease. The specific treatment of both syndromes resolved intestinal alterations and caused the diminution of the acute bronchitis frequent during the first and the second infancy.

[Williams-Beuren syndrome and celiac disease]. / Sindrome di Williams-Beuren associata a malattia celiaca.

The authors describe a case of Williams syndrome-Coeliac Disease that they have observed at the age of three years and 10/12. There are few reports in the literature. We focus on the variability of clinical and biochemical aspects of Williams Disease and the necessity for an adequate gastroenterologic follow-up (anti-gliadine antibody and anti-endomisium antibody) in these patients with little growth in terms of weight and height and intestinal alterations present in superior measure in companion with the reported standards for the same syndrome.

[Bacterial meningitis. Review of literature and retrospective study of 208 cases observed]. / Le meningiti batteriche. Revisione della letteratura e studio retrospettivo in 208 casi osservati.

Bacterial meningitis is a particularly dangerous infection of the central nervous system involving quite a number of mortal cases and frequent neurological sequelae. Etiology varies in relation to the patient's age. In the first 2 months of life Streptococcus B, Listeria monocytogenes, Escherichia coli and other Gram negative enteric bacilli are more frequently isolated while in older children Haemophilus influenzae, Neisseria meningitidis and Streptococcus pneumoniae are more common. Clinical symptoms take a different form according to the patient's age: symptoms of a general kind prevail in the first 2 months of life while in older children signs of meningeal irritation predominate. In a review of the survey of cases of bacterial meningitis observed at the Clinica Pediatrica in Pisa from 1970 to July 1993, with a retrospective research, 208 patients have been examined, considering age, etiology, clinical course especially observing the course of temperature, liquor characteristics, normalisation of the index of phlogosis, mortality and neurological sequelae. In the last ten years the availability of 3rd generation cephalosporin has provided the possibility of comparing two groups of patients of an age ranging between 1 month and 14 years. Twenty cases were treated with ampicillin and chloramphenicol and 30 cases with cephalosporins the evaluation made considering the course of temperature, the normalization of the liquor index has revealed a more favourable clinical course in the second group of patients.

[Celiac disease associated with chronic autoimmune hepatitis. Description of a case]. / Associazione tra malattia celiaca ed epatite cronica autoimmune. Descrizione di un caso.

The authors describe a case of coeliac disease and autoimmune chronic hepatitis in the same patient. Case description allows a critical review of the literature and evaluation of pathogenetic hypotheses.

[Plasma L-carnitine levels in children with celiac disease]. / Concentrazioni plasmatiche di L-carnitina in bambini celiaci.

Carnitine is a very important co-factor for the metabolism of fatty acids, because it is the necessary carrier for the passage of acyl groups inside the mitochondria, where beta-oxidation takes place. In the human body the total pool of carnitine is made by two fractions, one being endogenous and the second exogenous. The absorption of exogenous carnitine takes place mainly at duodenal-jejunal level by an active transport mechanism based on amino acid carrier. Plasma L-carnitine concentrations have been measured in 66 coeliac patients (mean age: 7 years and 4 months). Thirty three of them were on a free diet and the other 33 were on a gluten-free diet for at last six month. In 10 patients we studied plasma L-carnitine levels both on a free diet and on a gluten-free diet. As controls we examined 33 healthy children comparable for age. Plasma L-carnitine concentrations have been measured by a spectrophotometrical method according to Marquis and Fritz's technique and subsequently modified by Pearson and Seccombe. In the 66 coeliac patients the mean values of serum L-carnitine were significantly lower than those in the controls (p < 0.001). The levels were significantly lower in patients a free diet with respect to those on gluten-free diet (p < 0.01). The 10 subjects who were examined both on free diet and on gluten-free diet showed an increase of plasma concentrations in the latter condition.(ABSTRACT TRUNCATED AT 250 WORDS)

[24-hour esophageal pH-metry in the evaluation of gastroesophageal reflux pathology]. / La pH-metria esofagea delle 24 ore nella valutazione della patologia da reflusso gastroesofageo.

Gastro-esophageal reflux (GER) in infants was studied using 24-hour esophageal pH monitoring. Gastro-esophageal reflux was detected in 32/41 subjects. In our patients the main symptoms were vomiting, regurgitation, failure-to-thrive, chronic respiratory problems such as asthma, apnea, recurrent pneumonia. All patients with GER were treated appropriately with prone positioning and medical therapy (prokinetic agent and, eventually, ranitidine). Successful treatment of the reflux was obtained in all patients. In our opinion the 24-hour intraesophageal pH monitoring is a highly diagnostic test to identify the presence of GER and evaluate its gravity.