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Telaprevir is a novel NS3A/4A protease inhibitor approved in combination with ribavirin and peg-interferon alfa for the treatment of genotype-1 chronic hepatitis C. This drug is also known to be a potent cytochrome P450 3A and drug efflux protein ATP-binding cassette B1 (also called P-glycoprotein) inhibitor, and could therefore interact with immunosuppressive drugs. For this reason, a decrease in cyclosporine (CsA) dosage has been proposed when combining this drug with telaprevir. We report herein the case of an unpredictable lack of interaction between CsA and telaprevir in a liver transplant recipient. The decrease in CsA dosage, conducted as recommended in the literature, did not result in stable CsA concentrations but decreased them. However, the decrease in CsA exposure could have been unseen without the measurement of CsA concentrations 2 h after the administration (C2 ) of the drug, because it mainly resulted from the decrease in CsA peak. The mechanism leading to this lack of drug interaction in this patient has not been fully elucidated yet, but is likely to affect the absorption phase. Therapeutic drug monitoring using only CsA trough concentrations could be falsely reassuring, and the addition of the measurement of the C2 may add useful information to adapt CsA dosage in patients co-treated with telaprevir.

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Because both descriptions of species and modern human-driven extinctions started around the same time (i.e., eighteenth century), a logical expectation is that a large proportion of species may have gone extinct without ever having been recorded. Despite this evident and widely recognized assumption, the loss of undescribed species has never been estimated. We quantified this loss for several taxonomic groups and regions for which undescribed species extinctions are likely to have occurred. Across a wide range of taxonomic groups, we applied known extinction rates computed from recorded species losses to assumed exponential decay in the proportion of species remaining undiscovered. Because all previous modeling attempts to project total species richness implicitly assumed that undescribed species extinctions could be neglected, we also evaluated the effect of neglecting them. Finally, because we assumed constant description and extinction probabilities, we applied our model to simulated data that did not conform to this assumption. Actual species losses were severely underestimated by considering only known species extinctions. According to our estimates, the proportion of undiscovered extinct species over all extinctions ranged from 0.15 to 0.59, depending on the taxonomic group and the region considered. This means that recent extinctions may be up to twice as large as the number recorded. When species differed in their extinction or description probabilities, our model underestimated extinctions of undescribed species by up to 20%.

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Blood collected from 62 fetuses aged 20-38 weeks of gestation was studied. The values of ten lipid parameters were determined: cholesterol (TC), triglycerides (TGs), apolipoprotein A1 (apo A1), apolipoprotein B (apo B), apolipoprotein E (apo E), total apolipoprotein CIII (apo CIII), apolipoprotein CIII present in particles containing apo B (apo CIII LpB) or not (apo CIII Lp non-B), lipoparticles A1 (LpA1), and lipoprotein a (Lp(a)). The results show that, except for apo E, all the studied parameters were present in lower concentrations than in adults and newborns, and that Lp(a) is not detectable at that stage in life.

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In this paper randomization of well-known former mathematical models is proposed (i.e., the Hopfield model for neural networks and the Hahn model for the cell cycle) in order to facilitate the study of their asymptotic behavior: in fact, we replace the determination of the stability basins for attractors and boundaries by the study of a unique (or a small number of) invariant measure(s), whose distribution function maxima (or, respectively, percentile contour lines) correspond to the location of the attractors (or, respectively, boundaries of their stability basins). We give the name of "confinement" to this localization of the mass of the invariant measure(s). We intend to show here that the study of the confinement is in certain cases easier than the study of underlying attractors, in particular if these last are numerous and possess small stability basins (for example, for the first time we calculate the invariant measure in the random Hopfield model in a case for which the deterministic version exhibits many attractors, and in a case of phase transition). (c) 1995 American Institute of Physics.

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Helicobacter pylori gastritis usually manifests as recurrent abdominal pain but is sometimes discovered upon evaluation for digestive tract bleeding with severe anemia. An 11-year-old who was not under medication and had no history of pain was admitted for isolated regenerative anemia (5.6 g/dl) due to digestive tract bleeding. Laboratory tests showed only low serum iron and ferritin levels. Endoscopy disclosed hemorrhagic inflammation of the duodenal cap and antritis with a hillocky appearance. The diagnosis of H. pylori infection was established on the basis of the finding of curved Gram-negative rods on the smears and of a positive urea test. There was moderate interstitial antritis. The patient was given an H2 antagonist (ranitidine) and amoxicillin with tinidazole for six weeks. Serum IgG antibodies against H. pylori were found in the child's parents and siblings, with the exception of a 7 month old infant. A ten year old sister had been hospitalized two years earlier for hemorrhagic duodenitis ascribed at the time to use of acetylsalicylic acid. H. pylori has been reported in 40% to 95% of pediatric patients with primary gastritis. Physicians should be familiar with this frequent, often familial disease. Management rests on concomitant administration of two antimicrobials and an acid secretion inhibitor to the index patient and family members. Endoscopy is too invasive to be appropriate for monitoring the outcome. In practice, recovery is affirmed on the basis of resolution of clinical manifestations and decreased levels of anti-H. pylori antibodies.

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A fifteen-month-old child was admitted with a week history of isolated fever. On CSF (Cerebral Spinal Fluid) examination, hyperproteinorachy, hyperglycorachy and hypochlorurachy were found. The diagnosis of tuberculosis meningitis was suspected but usual tests were unable to find Mycobacterium tuberculosis in CSF, urine and sputum. Only the Polymerase Chain Reaction detected the Mycobacterium tuberculosis genome in the CSF. A specific treatment was started immediately. Apyrexia was obtained within 2 days; the outcome was favorable, without sequelae.

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Clinical, radiological and biological features of 19 cases of serologically proven Mycoplasma pneumoniae pneumonia were compared with those of 21 cases of other types of pneumonia. Some clinical features were more frequent in M pneumoniae: patients older than 5 years, association with upper respiratory tract infection, skin rashes, acute course, unsuccessful treatment with penicillin. There were no specific radiological features. When compared with the complement fixation method, the serological diagnosis using agglutination technique appears to be more sensitive.

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The treatment of insulin-dependent diabetes mellitus in a child generates new constraints in the family and requires adjustments of the daily routine. Refusal of these changes may lead to poor compliance with the treatment regimen. Poor or mistaken daily results and repeated episodes of ketoacidosis may occur as a result. Clandestine injection of insulin responsible for apparently inexplicable episodes of hypoglycemia is less common. Three new cases are reported herein. Clinical diagnosis is fairly easy and biological findings can provide confirmation. Acknowledgement of the injections by the patient is important in order to gain insight into his or her motives. Depression is known to be common among diabetics and the injections may be a symptom of depression. Another possibility is that the child expects to achieve an "irrational recovery" from the disease by taking control over the treatment. Furthermore, a child with access to a highly active drug like insulin can use this situation to acquire and maintain exceptional status within the family. The diagnosis of factitious hypoglycemia requires in every case an in-depth evaluation which may lead to psychotherapy for the child or for the entire family.

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BACKGROUND: Behçet's disease is rare in children and is exceptionally revealed by thrombophlebitis at this age of life. CASE REPORT: A girl, aged 13 years, was admitted after having suffered from thrombophlebitis of the right leg for 6 weeks. Her medical history included frequent attacks of aphthous stomatitis and conjunctivitis and one episode of iritis. At admission, thrombophlebitis with venous thrombosis was confirmed by Doppler; it was associated with aphthous gingivitis and two similar erosive lesions in the genital area. Technetium 99 perfusion scintiphotography revealed a right pulmonary embolism. The erythrocyte sedimentation rate was elevated but there was no change in coagulation factors or immunologic abnormalities, except for the presence of immune complexes and increased complement C3 component. Biopsy of the skin lesions showed vascularitis. There was no involvement of the eyes. The condition progressively improved with anticoagulant treatment for 1 year, followed by low doses of acetylsalicylic acid. CONCLUSION: Phlebothrombosis, a classic complication of Behçet's disease in adults, revealed the disease in this girl. Its mechanism remains unclear and duration of anticoagulant treatment is still debated.

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A nine year-old, mentally retarded girl was admitted because of growth retardation and recurrent respiratory infections. The lysosomal storage disease was ascertained by microscopic examination of bone marrow and gum biopsies. The diagnosis was provided by urine chromatography: the glycoasparagine Glc-Nac-Asn was characteristic of patients with aspartylglycosaminuria.

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We report the case of a child presenting with abdominal Burkitt's lymphoma in whom a relapse presented as orbital and muscle involvement. This clinical feature is extremely rare. Two muscle and one orbital biopsies were necessary to obtain proper diagnosis. A new extension check-up showed bone marrow invasion and normal cerebrospinal fluid. This relapse was successfully treated by conventional chemotherapy and consolidated with high-dose chemotherapy, total body irradiation and autologous bone marrow transplantation. Eighteen months after transplantation, the child may be considered as definitively cured.

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Among a group of children hospitalized for "joint pain", four of the cases of reactive arthritis were due to Yersinia infection. These four cases are described. Some patients had suggestive clinical symptoms but serologic studies were needed to establish the diagnosis. Tissue group studies showed that two children were HLA B27 and one was HLA B7. Reactive arthritis due to Yersinia in a form of "enteral arthritis". The prevalence of Yersinia arthritis has not been documented. Serologic tests are essential to outrule the main differential diagnosis, i.e. chronic juvenile arthritis (juvenile rheumatoid arthritis). Short-term resolution of symptoms is seen in every case. The long-term outcome is less well documented, especially with regard to the risk of recurrence and to relationships with peripheral joint disease and spondylarthropathies of early adulthood. HLA B27 positivity may be a risk factor. The pathogenesis of Yersinia-induced reactive arthritis is unclear; current studies are focusing on immunologic factors. The uncertainties concerning long-term outcome justifies renewed interest in childhood reactive arthritis.

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The case described is that of a 9-yr-old girl presenting with aspartylglycosaminuria. Diagnosis of this lysosomal storage disease was guided by histologic study of gingival specimen sampled in the course of dental care. Transmitted electron microscopy (TEM) revealed many vesicles and cellular inclusions, altered collagenic formations, associated with abnormal extracellular matrix. Gingival biopsy is easily performed, is noniatrogenic, leaves nor scar, and could be properly used to help diagnose metabolic diseases in children.

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Objectives of management of insulin-dependent diabetes mellitus in pediatric patients include elimination of symptoms, achievement of normal growth and maintenance of blood glucose levels close to normal values. Nutritional management can contribute to achievement of these goals. In non-overweight children with diabetes mellitus, energy intake should not be restricted and distribution of nutrients should be identical to that recommended in normal children. Except in specific circumstances, reduced intake of pure, sweet-tasting carbohydrates is desirable. The central point is appropriate distribution of the main meals and snacks throughout the day. Food intake should occur at the times of peak insulin activity to avoid both hypoglycemia and postprandial hyperglycemia. Nutritional recommendations for the child and family should be part of the general guidelines for healthy eating appropriate for all individuals. Nutrition education, as well as education on use of insulin, are components of a program aimed at providing the patient with knowledge and know-how. Correction of eating mistakes and optimal adjustment of insulin dosages are the two main aspects of daily therapy.

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Two patients with Turner's syndrome and Hashimoto's thyroiditis are described. The incidence of the karyotype 46 XX (iq), 45 X is high in this association reported in the literature; thus, 17 patients among 25 with Turner's syndrome and thyroiditis had a structural abnormality of the X chromosome. Routine thyroid antibodies determination should be carried out in patients with gonadal dysgenesis between 10 and 20 years of age, and early replacement therapy should be undertaken in Turner's syndrome with Hashimoto's thyroiditis, since clinical signs of hypothyroidism are usually delayed.

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We studied the height growth of 96 children presenting with acute leukemia or non Hodgkin lymphoma, together with an investigation of GH and TSH in 41 of them. There were 2 groups: group I consisting of 19 patients without brain irradiation and group II consisting of 77 patients with prophylactic brain irradiation. Initial average height was identical in both groups. Growth rate was significantly decreased in group II but not in group I (p less than 0.01). There is a correlation between the decrease of growth rate and the decrease of GH to arginine stimulation test (p less than 0.03). A lack of response to GRF-44 was noted in 4 of 11 investigated patients. TSH and prolactin secretions were unchanged.

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We report 2 cases of neonatal auto-immune thrombocytopenia treated with high-dose intravenous gamma-globulins. Efficacy of treatment was immediate, inducing an increase in platelet levels which was transitory during the first 2 weeks but stabilized in the third week. Tolerance was excellent. Injections of 400 mg/kg/day repeated for 4 to 5 days should be preferred to a single dose of 1 to 2 g/kg.

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