[Tick-borne encephalitis in a child in a nonendemic country: A case report]. / Méningo-encéphalite à tiques chez l'enfant en France : à propos d'un cas.

Tick-borne encephalitis (TBE) is an arbovirus induced by tick-borne encephalitis virus (TBEV) transmitted by tick bite. The disease is rare in France (two to three cases per year) but endemic zones extend from Western Europe to the east coast of Asia (10,000-15,000 cases per year). An 8-year-old boy was admitted to our pediatric ward in Strasbourg (France) for febrile headache with diplopia. Four days after a tick bite, he declared a febrile headache together with maculopapular rash on the elbows, knees, and cheeks. Fourteen days after the outbreak of symptoms, he showed confusion, drowsiness, and binocular diplopia. Brain MRI was normal and the electroencephalogram found diffuse slow activity with no discharge. Lumbar puncture found meningitis with 92 cells (60% neutrophils, 40% lymphocytes). The diagnosis was made with specific IgM and IgG antibody isolation in the serum (Elisa). Lyme serology was negative. The evolution was slowly favorable and the child remained hospitalized for 8 days. The neurological control examination 2 weeks later was normal except for a moderate left deviation during tandem walk and left Romberg manoeuver. Meningitis or meningoencephalitis in a child must raise the diagnosis of TBE in children, even in nonendemic countries, given the recent increased incidence of TBE and the development of tourism. Recent travel in endemic areas, a history of tick bite, and a clinical course in two phases must be sought. The diagnosis is serologic and prevention is based on vaccination.

[Hodgkin disease revealed by a nephrotic syndrome: A case report]. / Lymphome de Hodgkin révélé par un syndrome néphrotique : à propos d'un cas.

Pediatric nephrotic syndrome (NS) is most often idiopathic or primary but in rare cases, it can be secondary to neoplasia. We report on a case of steroid-resistant NS revealing as a paraneoplastic syndrome of Hodgkin disease (HD) in a 12-year-old boy. The onset of the NS can be earlier, later, or simultaneous to the HD. Treatment of the lymphoma allows the disappearance of the NS. In the case we observed, the diagnosis of HD was delayed because HD presented with an isolated, hilar adenopathy in the absence of retroperitoneal or peripheral locations. In children aged 10 years or more presenting with NS, steroid-resistant or otherwise, a possible paraneoplastic origin such as Hodgkin lymphoma should always be taken into consideration and eventually eliminated.

[Medication adverse events: Impact of pharmaceutical consultations during the hospitalization of patients]. / Évènements iatrogènes médicamenteux : impact des consultations pharmaceutiques en cours d'hospitalisation.

The medication iatrogenic events are responsible for nearly one iatrogenic event in five. The main purpose of this prospective multicenter study is to determine the effect of pharmaceutical consultations on the occurrence of medication adverse events during hospitalization (MAE). The other objectives are to study the impact of age, of the number of medications and pharmaceutical consultations on the risk of MAE. The pharmaceutical consultation is associated to a complete reassessment done by both a physician and a pharmacist for the home medication, the hospital treatment (3days after admission), the treatment during chemotherapy, and/or, the treatment when the patient goes back home. All MAE are subject to an advice for the patient, additional clinical-biological monitoring and/or prescription changes. Among the 318 patients, 217 (68%) had 1 or more clinically important MAE (89% drug-drug interaction, 8% dosing error, 2% indication error, 1% risk behavior). The patients have had 1121 pharmaceutical consultations (3.2±1.4/patient). Thus, the pharmaceutical consultations divided by 2.34 the risk of MAE (unadjusted incidence ratio, P≤0.05). Each consultation decreased by 24% the risk of MAE. Moreover, adding one medication increases from 14 to 30% as a risk of MAE on the population. Pharmaceutical consultations during the hospital stay could reduce significantly the number of medication adverse effects.

[Intra-articular osteoid osteoma in the left elbow]. / Ostéome ostéoïde du coude : un mode de révélation trompeur.

Intra-articular osteoid osteoma (OO) is a rare and difficult diagnosis. We report the case of an 11-year-old boy who presented with inflammatory monoarticular arthritis in the left elbow. This monoarthritis was resistant to all types of treatment. He had an OO, diagnosed late because the first symptoms developed subsequent to the ablation of a wart in the same elbow and were suggestive of arthritis.

[Focusing on peritoneal dialysis adequacy]. / Adéquation en dialyse péritonéale : mise au point.

The optimal method to assess the adequacy of peritoneal dialysis therapies is controversial. Today, the adequacy must not be considered as a number or a concept assessed only by two parameters (total KT/V urea and total solute clearance) but defined by many more items. In the absence of data, based on theoretical considerations, the reanalysis of the CANUSA study showed that renal kidney function, rather than peritoneal clearance, was associated with improved survival. Residual renal function is considered as a major predictor factor of cardiovascular mortality. Results of this reanalysis were supported by the adequacy data in ADEMEX, EAPOS and ANZDATA studies. Therefore, clinical assessment plays a major role in PD adequacy. The management of fluid balance, the regular monitoring of malnutrition, the control of mineral metabolism and particularly the glucose load, considered as the "corner-stone" of the system, are the main points to be considered in the adequacy of PD patients. The essential goal is to minimize glucose load by glucose-sparing strategies in order to reduce the neoangiogenesis of the peritoneal membrane.

A metabolomic view of how the human gut microbiota impacts the host metabolome using humanized and gnotobiotic mice.

Defining the functional status of host-associated microbial ecosystems has proven challenging owing to the vast number of predicted genes within the microbiome and relatively poor understanding of community dynamics and community-host interaction. Metabolomic approaches, in which a large number of small molecule metabolites can be defined in a biological sample, offer a promising avenue to 'fingerprint' microbiota functional status. Here, we examined the effects of the human gut microbiota on the fecal and urinary metabolome of a humanized (HUM) mouse using an optimized ultra performance liquid chromatography-mass spectrometry-based method. Differences between HUM and conventional mouse urine and fecal metabolomic profiles support host-specific aspects of the microbiota's metabolomic contribution, consistent with distinct microbial compositions. Comparison of microbiota composition and metabolome of mice humanized with different human donors revealed that the vast majority of metabolomic features observed in donor samples are produced in the corresponding HUM mice, and individual-specific features suggest 'personalized' aspects of functionality can be reconstituted in mice. Feeding the mice a defined, custom diet resulted in modification of the metabolite signatures, illustrating that host diet provides an avenue for altering gut microbiota functionality, which in turn can be monitored via metabolomics. Using a defined model microbiota consisting of one or two species, we show that simplified communities can drive major changes in the host metabolomic profile. Our results demonstrate that metabolomics constitutes a powerful avenue for functional characterization of the intestinal microbiota and its interaction with the host.

Ventriculoperitoneal shunts in children on peritoneal dialysis: a survey of the International Pediatric Peritoneal Dialysis Network.

OBJECTIVE: The aim of this study was to inform best evidence-based practice by collating and disseminating the experiences of members of the International Pediatric Peritoneal Dialysis Network with children having concurrent ventriculoperitoneal shunts (VPS) and peritoneal dialysis catheters (PDC). METHODS: An online questionnaire was created and distributed to all 135 centers participating in the International Pediatric Peritoneal Dialysis Network; the overall response rate was 56 %. RESULTS: A total of 18 patients with a concurrent VPS and PDC were reported. The children were 0-12 (mean 6.8) years old at the time of placement of the second indwelling device (PDC or VPS). In 15 cases, the PDC was inserted post-VPS. On average, the two catheters were present concurrently for 23 (range 1-60) months. There were 20 episodes of peritonitis observed in 11 of the 18 patients during a period of 392 months at risk, which is a peritonitis rate of 1/19.6 months. Only one patient developed both a VPS infection and an episode of peritonitis, and these events were temporally unrelated. No episodes of an ascending shunt infection or meningitis occurred in association with any episode of peritonitis, and no other complications of catheter dysfunction were described. CONCLUSIONS: The rate of peritonitis, the absence of any documented ascending or descending infections and the lack of catheter dysfunction during the period of observation suggests that the presence of, or need for, a VPS should not preclude PD as a safe option for children requiring renal replacement therapy.

Mutations in SDCCAG8/NPHP10 Cause Bardet-Biedl Syndrome and Are Associated with Penetrant Renal Disease and Absent Polydactyly.

The ciliopathies are an expanding group of disorders caused by mutations in genes implicated in the biogenesis and function of primary cilia. Bardet-Biedl syndrome (BBS) is a model ciliopathy characterized by progressive retinal degeneration, obesity, polydactyly, cognitive impairment, kidney anomalies and hypogonadism. Mutations in SDCCAG8(NPHP10) were described recently in patients with nephronophthisis and retinal degeneration (Senior-Loken syndrome; SLS). Given the phenotypic and genetic overlap between known ciliopathy genes, we hypothesized that mutations in SDCCAG8 might also contribute alleles to more severe, multisystemic ciliopathies. We performed genetic and phenotypic analyses of 2 independent BBS cohorts. Subsequent to mutation screening, we made a detailed phenotypic analysis of 5 families mutated for SDCCAG8 (3 homozygous and 2 compound heterozygous mutations) and conducted statistical analyses across both cohorts to examine possible phenotype-genotype correlations with mutations at this locus. All patients with mutations in SDCCAG8 fulfilled the diagnostic criteria for BBS (retinal degeneration, obesity, cognitive defects, renal failure, hypogonadism). Interestingly, none of the patients with primary SDCCAG8 mutations had polydactyly, a frequent but not obligatory BBS feature. In contrast, the same patients displayed early-onset renal failure, obesity, as well as recurrent pulmonary and ENT infections. Comparison of the phenotypes of these families with our entire BBS cohort indicated that renal impairment and absent polydactyly correlated significantly with causal SDCCAG8 mutations. Thus, SDCCAG8 mutations are sufficient to cause BBS in 1-2% of our combined cohorts, and define this gene as the sixteenth BBS locus (BBS16). The absence of polydactyly and the concomitant, apparently fully penetrant association with early kidney failure represents the first significant genotype-phenotype correlation in BBS that potentially represents an indicator for phenotype-driven priority screening and informs specific patient management.

[Dapsone for chronic skin lesions in 3 children suffering from Henoch-Schönlein vasculitis]. / Traitement par la dapsone des formes cutanées chroniques du purpura rhumatoïde : à propos de 3 cas.

We describe 3 cases of chronic purpuric skin lesions in children suffering from systemic vasculitis: 3 children with Henoch-Schönlein purpura. Dapsone was introduced when skin lesions were recurrent, extensive, and persistent, due to its known ability to act as an anti-IgA and as an anticytotoxic agent against polynuclear neutrophils. Fast and complete but purely suspensive healing of skin lesions was noted. One child developed methemoglobinemia, a known side-effect of dapsone, highlighting the need for adequate prescription and follow-up.

Peritoneal dialysis tailored to pediatric needs.

Consideration of specific pediatric aspects is essential to achieve adequate peritoneal dialysis (PD) treatment in children. These are first of all the rapid growth, in particular during infancy and puberty, which must be accompanied by a positive calcium balance, and the age dependent changes in body composition. The high total body water content and the high ultrafiltration rates required in anuric infants for adequate nutrition predispose to overshooting convective sodium losses and severe hypotension. Tissue fragility and rapid increases in intraabdominal fat mass predispose to hernia and dialysate leaks. Peritoneal equilibration tests should repeatedly been performed to optimize individual dwell time. Intraperitoneal pressure measurements give an objective measure of intraperitoneal filling, which allow for an optimized dwell volume, that is, increased dialysis efficiency without increasing the risk of hernias, leaks, and retrofiltration. We present the concept of adapted PD, that is, the combination of short dwells with low fill volume to promote ultrafiltration and long dwells with a high fill volume to improve purification within one PD session. The use of PD solutions with low glucose degradation product content is recommended in children, but unfortunately still not feasible in many countries.

Domestic activities after myocardial infarction. Their impact is underestimated.

BACKGROUND: Although aptitude for resumption of work is usually evaluated after myocardial infarction, the return home often entails significant daily obligations whose cardiovascular implications are poorly described and may well be underestimated. AIM: The aim of this study was to evaluate the consequences of domestic activities on blood pressure and heart rate in patients with recent myocardial infarction DESIGN: This was an observational study. SETTING: Inpatients, at the end of a three week period of cardiovascular rehabilitation. POPULATION: Patients with recent myocardial infarction. METHODS: We studied patients who had benefited from a three-week period of cardiovascular rehabilitation after a myocardial infarction, all treated with beta-blockers. At the end of the rehabilitation period, patients were submitted to a standardized exercise test with measurement of V.O2. They also carried out, on a separate day, four standardized domestic tasks in a random order along with an automated measurement of blood pressure and heart rate. RESULTS: We included 16 men and 11 women, aged 35 to 74 years. Vacuum cleaning led to a much greater increase in the product of heart rate and systolic blood pressure (DP) than did window cleaning, bathroom cleaning or ironing. It also led to an increase in heart rate to 70-90% of maximum heart rate during the exercise test and 47-65% of the maximal DP on the exercise test. Although the women were more accustomed to these tasks than the men, they did not appear to benefit from any training effect. The average level of DP observed in some patients during domestic tasks was comparable to that of a maximum exercise test indicating that they were not adequately prepared for a return to household activities. CONCLUSION: Domestic tasks should not be underestimated as they can lead to a significant increase in DP. They tend not to be taken into account in the rehabilitation of patients after a myocardial infarction. CLINICAL REHABILITATION IMPACT: The traditional methods of rehabilitation are not well adapted for resumption of domestic life, especially for women who are most involved in these activities. We recommend an individual approach involving performance of real life tasks taking account of the personality of the patients, their lifestyle and home environment.

Metabolic fate of ultratrace levels of GeCl(4) in the rat and in vitro studies on its basal cytotoxicity and carcinogenic potential in Balb/3T3 and HaCaT cell linesdagger.

The use of germanium (Ge) and the possibility of exposure to trace and ultratrace amounts of this element is increasing. Germanium is widely used in the industrial field as a semiconductor and also as a dietary supplement, an elixir to 'promote health and cure disease' (e.g. cancer and AIDS). More recently, germanium nanoparticles, ranging in size from 60 to 80 nm, have been developed as a potential spleen imaging agent. Like other metal-based nanoparticles used in nanomedicine, Ge nanoparticles may release trace and ultratrace amounts of Ge ions when injected. The metabolic fate and toxicity of these ions still needs to be evaluated. In this study the metabolic fate of a cationic tetravalent Ge species was studied in vivo by injecting rats i.p. with ultratrace amounts of Ge (80 ng kg(-1)) as [(68)Ge]GeCl(4). The cytotoxicity and carcinogenic potential was assessed in vitro using immortalised human skin keratinocytes and mouse fibroblasts (HaCaT and Balb/c 3T3 cell lines, respectively). At 24 h post-exposure Ge was poorly retained in rat tissues (kidney, liver, intestine, femur, spleen and the heart were the organs with the highest Ge concentration). In the blood, Ge was rapidly cleared, being almost equally distributed between plasma and red blood cells. The excretion was mainly via the urine. The hepatic and renal intracellular distribution showed the highest recovery of Ge in the cytosol and the nuclear fractions. Chromatographic separation and ultrafiltration experiments on kidney and liver cytosols showed that the bulk of Ge was associated with low molecular weight components, representing a 'mobile pool' of the element in the body. However, a significant part of the element was able to interact with biological macromolecules which could be responsible for the presence of Ge in the liver and kidney after 7 days. The in vitro experiments confirmed the low degree of cytotoxicity of GeCl(4) both in HaCaT and Balb/3T3. The latter model was more sensitive to the toxic effects induced by Ge as shown by a colony forming efficiency (CFE) greater than 70% at 700 microm of exposure. At the highest exposure concentration tested (700 microm) GeCl(4) failed to induce morphological neoplastic transformation of the cells, suggesting for the first time that a cationic form of Ge ions has no carcinogenic potential. This supports the results of the only study reported in mice, treated orally long-term to an anionic species of Ge such as sodium germanate (Kanisawa and Schroeder, 1967).

A comparative study of different release apparatus in generating in vitro-in vivo correlations for extended release formulations.

The importance of hydrodynamics in the development of in vitro-in vivo correlations (IVIVCs) for a BCS Class II compound housed in a hydrophilic matrix formulation and for a BCS Class I compound housed in an osmotic pump formulation was assessed. In vitro release data were collected in media simulating the fasted state conditions in the stomach, small intestine and the ascending colon using the USP II, the USP III and the USP IV release apparatuses. Using the data collected with the USP II apparatus, the plasma profiles were simulated and compared with human plasma profiles obtained after administration of the same dosage forms to healthy fasted volunteers. Data obtained with the USP III and USP IV apparatuses were directly correlated with the deconvoluted human plasma profiles. In vitro hydrodynamics affected the release profile from the hydrophilic matrix. For both formulations, based on the values of the difference factor, all three apparatuses were equally useful in predicting the actual in vivo profile on an average basis. Although some hydrodynamic variability is likely with low solubility drugs in hydrophilic matrices, the hydrodynamics of USP II, III and IV may all be adequate as a starting point for generating IVIVCs for monolithic dosage forms in the fasted state.

In-center daily on-line hemodiafiltration: a 4-year experience in children.

Our daily dialysis program was started in September 2002: in-center daily on-line hemodiafiltration (DIH) was carried out in 3-hour sessions, 5 - 6 times weekly, on-line assessment KT/Vurea of minimal 1.5 per session, polysulfone membranes. 12 children were included: median age 7.4 years (2.10 - 16.8 years), renal residual function less than 3 ml/min/1.73 m2 (Kcreat + Kurea/2), vascular access central catheter (n = 4) or fistula (n = 8), 7/12 being converted from peritoneal dialysis to DIH. Median follow-up on DIH was 11 months (4 - 43 months), endpoint was kidney transplantation (11/12) or transfer to another center (1/12). Monthly assessments of dialysis parameters (KT/Vurea, predialysis phosphatemia), diet survey (3 consecutive days), medications (number of antihypertensive drugs, phosphate chelators, potassium chelators) and statural growth were performed. At start of DIH, diet intake due to medical prescription and limited appetite was restrictive with limitation in water, salt (20 mmol/day), potassium and proteins (median 35 g/day, range 20 - 80 g); only 2/12 children were free of antihypertensive drugs, all received phosphate and potassium chelators, and growth retardation occurred (7/12 in prepubertal children, median height SDS -1.52) despite rhGH therapy (5/12 patients). At the end of DIH, diet was free, protein intake high (2 - 3 g/kg/day, range 30 - 100), 10/12 children were free of antihypertensive drugs, 4/12 received potassium chelators, 1/12 received phosphate chelators. All the prepubertal children at inclusion (n = 7) showed catch-up growth with a median growth rate of 0.8 cm/month (0.5 - 1.6 cm/ month). DIH allowed to maintain predialysis phosphatemia in a low normal range (median 1.23 mmol/l, range 1.65 - 0.63), without (11/12 children) need of phosphate chelators. Thanks to DIH children, parents and team care discovered during DIH a new way of life with motivated children, showing natural compliance (no diet restriction, no or few drugs), and most of all children developing with catch-up of growth.

Worldwide variation of dialysis-associated peritonitis in children.

Peritonitis is the most common cause of dialysis failure in children on chronic peritoneal dialysis. We performed a prospective study of 501 peritonitis episodes in 44 pediatric dialysis centers located in 14 countries that examined peritonitis etiology, efficiency of opinion-based management guidelines, and final outcomes. Culture-negative incidence varied significantly from 11% in North America to 67% in Mexico. Argentina and North America had the highest rate of Gram-negative episodes. Pseudomonas-based peritonitis was eightfold more common in the United States than in Europe, and correlated with the frequency of exit site cleansing and topical mupirocin administration. Significant regional variation in antibiotic susceptibility was noted for the first generation cephalosporins and aminoglycosides. Initial response rates to standardized empiric antibiotic treatment did not differ between regions; however, final outcomes were significantly less favorable in Eastern Europe. The wide regional variation in culture-negative peritonitis, and the distribution and antibiotic susceptibilities of causative bacteria needs to be taken into consideration when the guidelines for empiric therapy of pediatric dialysis-associated peritonitis are revised.

An allograft inflammatory factor 1 (AIF1) single nucleotide polymorphism (SNP) is associated with anticentromere antibody positive systemic sclerosis.

OBJECTIVE: To identify genetic associations between allograft inflammatory factor 1 (AIF1) and systemic sclerosis (SSc), or its subsets, using a single nucleotide polymorphism (SNP) in a replicate case-control study. METHODS: The frequencies of alleles and genotypes of an SNP, rs2269475, for the AIF1 gene were examined in two large independent cohorts of SSc patients (n = 1015 total), and compared with two groups of normal controls (n = 893 total). Both cases and controls were stratified by ethnicity (Caucasian, African American and Hispanic) and by autoantibody status [anti-centromere antibodies (ACA) and anti-topoisomerase I antibody (ATA)]. RESULTS: The minor T allele and CT/TT genotype frequencies of the AIF1 SNP were not observed more frequently in SSc patients of the three ethnic groups (individually or combined) when compared with controls. On the other hand, T and CT/TT frequencies were significantly increased in ACA-positive Caucasian SSc patients, and all ACA-positive SSc patients (the three ethnic groups combined), when compared with ACA-negative SSc patients and with normal controls, with odds ratios of approximately 1.5. CONCLUSION: The data demonstrate a genetic association between AIF1 and the ACA-positive subset of SSc. This polymorphism is a non-synonymous substitution and therefore likely to represent an important functional change in AIF1. Since vascular pathology is a prominent feature in ACA-positive SSc patients, the observed association with a vasculotrophic inflammatory gene is biologically plausible and warrants further research.