[Symptoms of Celiac disease in childhood]. / Les manifestations de la maladie cœliaque chez l'enfant.

The knowledge regarding celiac disease has increased dramatically in recent years, due to the availability of accurate serologic markers. Mass screening studies have shown that the prevalence of sensitization can be as high as 1/80. The range of symptoms is wide, from the classic growth failure, denutrition and diarrhea in infancy to clinically and histologically asymptomatic sensitized subjects. The interest of a routine mass screening is debated. The classical celiac disease in infancy is well known. Atypical symptoms and potentially associated disease are more frequent and potentially confounding. Physicians should be aware of any clue for celiac disease in atypical cases in order to improve the diagnostic yield, and therefore avoiding short or long term consequences.

[Recommendations for the management of bone demineralization in cystic fibrosis]. / Recommandations pour la prise en charge de la déminéralisation osseuse dans la mucoviscidose.

A high prevalence of low bone mineralization is documented in adult patients with cystic fibrosis (CF). Osteopenia is present in as much as 85% of adult patients and osteoporosis in 13 to 57% of them. In children, studies are discordant probably because of different control database. Denutrition, inflammation, vitamin D and vitamin K deficiency, altered sex hormone production, glucocorticoid therapy, and physical inactivity are well known risk factors for poor bone health. Puberty is a critical period and requires a careful follow-up for an optimal bone peak mass. This review is a consensus statement established by the national working group of the French Federation of CF Centers to develop practice guidelines for optimizing bone health in patients with CF. Recommendations for screening and for calcium, vitamin D and K supplementation are given. Further work is needed to define indications for treatment with biphosphonates and anabolic agents.

Ensuring good governance to address emerging and re-emerging animal disease threats: supporting the veterinary services of developing countries to meet OIE international standards on quality.

As an effect of increased globalisation, animal diseases, in particular those transmissible to man, have an immediate global economic and social impact. This fact, dramatically illustrated by the current avian influenza epizootic in South-East Asia and Eastern Europe, clearly demonstrates the crucial importance of the national Veterinary Services (VS) for the prevention, early detection and response for the efficient control of animal diseases. Complying with this mission for the VS presupposes the existence of appropriate governance and legislation and of an official system to control their quality and reliability- an obvious weakness in many developing and in transition countries. The World Organisation for Animal Health (OIE) has therefore developed a project aiming at strengthening the VS in those countries facing the greatest animal health threats and to bring them into line with OIE international standards already adopted by the same countries. Based on the evaluation of the VS and subsequent actions at the global, regional and national levels, the project will have a significant beneficial impact on the targeted countries as well as the international community as a whole, not only in the fields of agriculture, food security and production, and food safety, but also for the local and global prevention of emerging and re-emerging diseases of veterinary and public health importance. The project will be implemented in strong collaboration with the Food and Agriculture Organization. The actions proposed must be considered eligible for the concept of International Public Good.

[Peritonitis as a first manifestation of Neisseria type C meningitis]. / Péritonite révélatrice d'une méningite à méningocoque de type C.

A 15-year-old boy was first referred for a clinical presentation of revealed peritonitis. Abdominal endoscopy showed normal appendix but the presence of purulent peritoneal fluid. Antibiotics were immediately administered. Ten hours later clinical signs of meningitis occurred, and lumbar puncture was performed. CSF bacterial meningitis characteristics were present but no bacteria was observed. However Neisseria meningitidis type C was detected by direct peritoneal fluid examination and by 24(th) hour blood culture. Peritoneal and the CSF fluid culture were negative, but DNA analysis from peritoneal fluid was positive.

[Calcium and D vitamin status in toddlers: original study performed in the area of Rouen]. / Statut calcique et vitaminique D des enfants d'âge préscolaire. A propos d'une enquête pratiquée en région rouennaise.

Few data are available regarding calcium and vitamin D intake in toddlers, despite a remaining high growth velocity. Therefore, a study was carried out in the Rouen geographical area where the sunshine is limited. It appears that a great majority of the children studied (9/10) received plain milk, and subsequently only small quantities of vitamin D or calcium enriched milk. Nevertheless, 12% of primarily 4 to 6 year-old children do not received daily minimum requirements, and 6% of them had vitamin D insufficiency, which was demonstrated by 25OHD plasma concentrations. These concentrations declined from 18 months to 6 years old were related to discontinuation in vitamin D supplements. A great variability was observed in vitamin D supplementation as no official recommendations were followed. Modalities of this supplementation should be reconsidered.

Coupling defect of thyrotropin receptor and adenylate cyclase in a pseudohypoparathyroid patient.

A patient with type I pseudohypoparathyroidism was found to have mild hypothyroidism. The patient had an elevated basal TSH level and an exaggerated TSH response to TRH. There was no goiter despite increased TSH levels, and the 131I thyroidal uptake was low before and after exogenous TSH administration. These studies suggested that the patient might have partial resistance to TSH. The binding of radioiodinated TSH to thyroid membranes obtained by biopsy was next studied. The displacement of iodinated TSH by unlabeled TSH was found to be identical to that in normal control membranes. The adenylate cyclase stimulation by a supramaximal dose of TSH, however, was blunted (120.1 +/- 11.5 vs. 387.2 +/- 40.3 pmol cAMP/min/mg protein), while basal and NaF-stimulated activities were quite similar to the activities in normal membranes. These findings suggested a lack of signal transmission between the TSH receptor and the catalytic unit. Incubation of control membranes with TSH and GTP resulted in a synergistic effect on the adenylate cyclase activity. This was not found with the patient's membranes and suggested that the coupling failure was due to a defective guanine nucleotide regulatory protein. We conclude that in this case of type I pseudohypoparathyroidism, the associated mild primary hypothyroidism was due to a partial TSH refractoriness caused by a coupling defect between the TSH receptor and adenylate cyclase. This observation suggests that a common pathogenetic mechanism might underly type I pseudohypoparathyroidism and its associated hypothyroidism.

Resistance to the lipolytic action of epinephrine: a new feature of protein Gs deficiency.

Deficiency of protein Gs (Gs; OMIM no.103580), the stimulatory regulator of adenylyl cyclase, is associated with resistance to PTH and other hormones, sc calcifications, short stature, and skeletal defects (Albright's hereditary osteodystrophy). It is caused by heterozygous loss of function mutations in GNAS 1, the gene encoding the alpha-subunit of Gs. Obesity is a classical feature of patients with Gs deficiency, but the mechanism leading to fat accumulation has not been elucidated. We measured glycerol flux, using a nonradioactive tracer dilution approach, to analyze the lipolytic response to epinephrine in 6 patients with Gs deficiency and PTH resistance and compared it to six age-matched normal controls and nine massively obese children. Basal glycerol production was reduced by 50%, and lipolytic response to epinephrine was reduced by 67%, in Gs-deficient children, as compared with controls. The degree of impairment of lipolysis was similar in Gs-deficient children who were only moderately overweight and in morbidly obese children. These findings extend the spectrum of hormonal resistance in Gs deficiency. Besides beta-adrenergic receptors, Gs protein itself should be examined as a possible step involved in the decreased lipolysis observed in common obesity.

Ontogeny of somatostatin binding sites in respiratory nuclei of the human brainstem.

The ontogeny of somatostatin binding sites was studied in 16 respiratory nuclei of the human brainstem, from 19 postconceptional weeks to 6 months postnatal, by quantitative autoradiography using [(125)I-Tyr0,DTrp8]S14 as a radioligand. In the early gestational stages (19-21 postconceptional weeks), moderate to high concentrations of [(125)I-Tyr0,DTrp8]S14 binding sites were found in all nuclei, the highest density being measured in the locus coeruleus. From 19 weeks of fetal life to 6 months postnatal, a decrease in the density of labeling was observed in all nuclei. The most dramatic reduction in site density (80-90%) was found in the ventral part of the nucleus medullae oblongata lateralis and in the nucleus paragigantocellularis lateralis. A 70-80% decrease was detected in the dorsal part of the nucleus tractus solitarius, the nucleus nervi hypoglossi, the ventral part of the nucleus medullae oblongatae centralis, the nucleus ambiguus, the nucleus paragigantocellularis dorsalis, and the nucleus gigantocellularis, and a 60-70% decrease in the nucleus parabrachialis medialis, the ventrolateral and ventromedial parts of the nucleus tractus solitarius, and the nucleus praepositus hypoglossi. A 50-60% decrease was observed in the caudal part of the nucleus tractus solitarius, the nucleus dorsalis motorius nervi vagi, and the nucleus parabrachialis lateralis, whereas in the nucleus locus coeruleus, the concentration of recognition sites decreased by only 30%. The profiles of the decrease in site density differed in the various structures. In the majority of the nuclei, a gradual diminution of binding density was observed either throughout the developmental period studied or mainly during fetal life. Conversely, in two nuclei, i.e., the nucleus parabrachialis lateralis and the locus coeruleus, an abrupt decrease occurred around birth. The differential decrease in the density of somatostatin binding sites observed in respiratory nuclei during development, together with the observation that microinjection of somatostatin in some of these nuclei causes ventilatory depression and apnea, strongly suggests that the somatostatinergic systems of the human brainstem are involved in the maturation of the respiratory control.

Increased density of somatostatin binding sites in respiratory nuclei of the brainstem in sudden infant death syndrome.

Sudden infant death syndrome is the primary cause of mortality in children aged one to six months in industrialized countries. Although the etiology of this syndrome is still unknown, subtle abnormalities in the neuronal circuitry involved in the control of respiratory activity are suspected. Since stereotaxic administration of somatostatin in the brainstem of rat and cat produces fatal apnea, we have compared the densities of somatostatin binding sites in the respiratory centers of 11 cases of sudden infant death syndrome and six control infants without neuronal disease. The density of binding sites was measured in 17 structures of the pons and medulla oblongata by means of quantitative in vitro autoradiography using iodinated [Tyr0,D-Trp8]somatostatin-14 as a radioligand. The density of somatostatin binding sites was significantly higher in the medial and lateral parabrachial nuclei in the sudden infant death syndrome group than in the control group. In six other nuclei, the median of the receptor density was higher in the sudden infant death syndrome group than the maximum values measured in the control group. The presence of high concentrations of somatostatin binding sites in several respiratory nuclei of the brainstem in approximately half of the sudden infant death syndrome victims suggests that the decrease in receptor density that normally occurs during ontogeny was delayed in these infants. In particular, the high level of somatostatin binding sites in the medial and lateral parabrachial nuclei of sudden infant death syndrome suggests that the delayed maturation of these receptors may be associated with a deficit of the hyperventilatory response to hypoxia.

Anatomical distribution of somatostatin receptors in the brainstem of the human fetus.

The distribution of somatostatin binding sites was studied in the pons and medulla oblongata of three human fetuses (gestional ages 26, 28 and 30 weeks). The study was carried out by in vitro quantitative autoradiography using either [125I-Tyr0,D-Trp8]somatostatin-14 or [125I-Tyr11]somatostatin-14 as radioligands. Somatostatin binding sites were observed in a number of nuclei subserving sensory, motor or integrative functions within the pons and medulla. In addition, discrete tracts also contained significant amounts of binding sites. Among structures involved in sensory processes, a high density of binding sites (40-60 fmol/ mg wet tissue) was measured in the dorsal cochlear nucleus and in the nucleus tractus spinalis trigemini caudalis. Moderate to high levels of binding sites (30-40 fmol/mg wet tissue) were detected in the other sensory cranial nerve nuclei. A moderate density of sites (15-30 fmol/mg wet tissue) was measured in most motor nuclei, the highest concentrations being observed in the dorsal motor nucleus of the vagus nerve, the facial nucleus, the hypoglossal nucleus and the nucleus ambiguus. The griseum pontis and the nucleus corporis pontobulbaris contained very high (> 60 fmol/mg wet tissue) and high concentrations of somatostatin binding sites, respectively, while the other relay nuclei contained low to moderate levels of binding. In monoaminergic nuclei, very high and moderate to high concentrations of somatostatin binding sites were measured in the nucleus locus coeruleus and in its dorsal subnucleus, respectively. Moderate densities of sites were detected in the ventral subnucleus of the nucleus locus coeruleus and in the different parts of the raphe. In the white matter, low levels of binding were measured in the inferior cerebellar peduncle, the lateral and median lemnisci and the tractus solitarius. Conversely, moderate to high concentrations of somatostatin binding sites were measured in the median and superior cerebellar peduncles. The pyramis contained a very high density of recognition sites. A marked heterogeneity in the density of binding sites was observed within a few structures particularly in the medial accessory olivary of nucleus and the medial longitudinal fasciculus. Selective ligands were used to determine the pharmacological profile of the [Tyr11]somatostatin-14 binding sites in various brainstem regions. In the dorsal cochlear nucleus and the pyramis, all somatostatin binding sites belonged to the SSA subtype. Conversely, in the lateral paragigantocellular nucleus, all somatostatin binding sites belonged to the SSB subtype. The other regions studied contained various proportions of SSA and SSB subtypes. In conclusion, the present study shows that high concentrations of somatostatin receptors are present in many regions of the human fetus brainstem. These data support the concept that somatostatin could be involved in the maturation of brain structures.

Immunogenicity and safety of a new liquid hexavalent combined vaccine compared with separate administration of reference licensed vaccines in infants.

OBJECTIVE: The immunogenicity and safety of a new liquid hexavalent vaccine (diphtheria-tetanus-acellular pertussis-inactivated polio vaccine-hepatitis B-polyribosyl ribitol phosphate conjugated to tetanus protein; Hexavac; Aventis Pasteur MSD, Lyon, France) are compared with those of reference vaccines [diphtheria-tetanus-acellular pertussis-inactivated polio vaccine reconstituting lyophilized purified Haemophilus influenzae polysaccharide conjugated to tetanus protein vaccine (Pentavac; Aventis Pasteur MSD) and hepatitis B vaccine (H-B-Vax II; Aventis Pasteur MSD)] injected separately at the same visit in a prospective multicenter, comparative, open label trial. METHODS: Infants were randomized to receive Hexavac (n = 423) or Pentavac and H-B-Vax II (n = 425) as a primary immunization series at 2, 4 and 6 months of age. Seroprotection and seroconversion rates against all antigens at 1 month after the primary series were compared between the two vaccine groups with 95% confidence intervals (CI0.95) and were considered clinically equivalent (not inferior) when the upper limit of the 95% confidence interval on the difference (reference, hexavalent) was below predefined differences. RESULTS: Hexavac met and surpassed the pre-defined criteria for clinical equivalence to Pentavac and H-B-Vax II given concomitantly. It elicited similar seroprotection and seroconversion rates against all antigens. Seroprotection and seroconversion rates obtained 1 month after the third dose of Hexavac were >90% for all antigens. The postimmunization antibody geometric mean titers (GMT) for hepatitis B and purified Haemophilus influenzae polysaccharide were about 2-fold higher in infants who received the reference vaccines than in infants who had received Hexavac. GMTs for poliovirus antibodies tended to be enhanced in infants vaccinated with Hexavac. GMTs for all other antigens were very similar among both groups. Hexavac was generally well-tolerated. At least one local reaction was reported in 20.3% of Hexavac injections compared with 15.8% at the Pentavac injections site and 3.8% at the H-B-Vax II injections site. These reactions were generally mild and transient. At least one systemic adverse event was reported in 45.7% of Hexavac injections compared with 42.2% of Pentavac and H-B-Vax II injections (mild fever, irritability and drowsiness were most frequently reported). The frequency of adverse events was not significantly different between groups. No vaccine-related serious adverse event occurred during the study. CONCLUSION: This liquid hexavalent vaccine was generally well-tolerated and provided immune responses adequate to be protective against six infectious diseases with a single injection, given at 2, 4 and 6 months of age.

Vitamin D supplementation in pregnancy: a controlled trial of two methods.

A randomized study was conducted to evaluate the effects of single-dose and daily vitamin D supplementation in pregnant women during the last trimester of a winter pregnancy in the Northwest of France. The women were divided into three randomized groups: one (N = 21) was given a vitamin D2 supplement of 1000 IU/day during the last three months of pregnancy, one (N = 27) was given a single oral dose of 5 mg at the seventh month of pregnancy, and one (N = 29) acted as a control. Venous plasma samples were obtained at delivery from the women and from cord blood, and levels of calcium, 25-OHD, and 1,25(OH)2D were determined. No significant difference in plasma calcium concentration was found among the three groups, but within each group plasma calcium concentrations were higher in the cord samples than in the respective maternal samples. The levels of the two metabolites measured were consistently lower in the cord samples than in the respective maternal samples. Cord 25-OHD concentrations correlated with those of maternal plasma. No significant modification of maternal calciuria or of the birth weight of term infants was observed. 25-OHD concentrations were greater in maternal and cord plasma from treated mothers, but only a slight difference was observed between the supplemented groups. 1,25(OH)2D concentrations were not significantly different in the three groups. A single 5-mg dose of vitamin D given orally at the seventh month of pregnancy provides effective prophylaxis in the authors' region.

Dominantly inherited ureteropelvic junction obstruction.

We report on siblings from two families with unilateral ureteropelvic junction obstruction. HLA studies were undertaken and found to be a useful marker between affected members. We believe that incomplete penetrance with variable expression is the most probable mode of transmission of this disorder.

Financial risk and hospital cost for elderly patients in non-age stratified urology DRGs.

The Diagnostic Related Group (DRG) hospital payment system may be inequitable for certain groups of Medicare patients. This study of 216 Medicare urology patients in the ten non-age stratified urology DRGs demonstrated that patients seventy years of age and older (70+) had higher resource consumption than patients under seventy years of age (70-). Findings were: (1) older patients (70+) had higher total hospital costs (+12,022 per patient) than younger patients (70-) (+9,872 per patient); (2) a longer hospital length of stay (14.2 days vs 11.6 days); (3) financial risk of +1,756 loss per (70+) patient vs +1,309 profit per (70-) patient (p less than 0.05); (4) more diagnoses and procedures per patient, and (5) a higher mortality (4.0% vs 3.3%). These findings suggest that the current DRG scheme may be inequitable vis-a-vis the older urology patient in non-age stratified DRGs, and thus could limit access and quality of care for these patients in the future.

Comparison of two oral rehydration solutions in eutrophic infants with moderate acute diarrhea: results of an interim analysis.

A randomized, multicenter clinical trial comparing two oral rehydration solutions (ORS) with different sugar content and total osmolality was carried out in France. Solution A had 168 mmol/L of sugar and a total osmolarity of 326 mosm/kg; solution D had 90 mmol/L of sugar and a total osmolarity of 240 mosm/kg. Weight gain, stool output, and biologic variables were analyzed. This interim analysis included 49 infants (27 in group A and 22 in group D). Patients in both groups gained weight without any significant difference between the two ORS. Between admission and day 4, the overall number of stools and the number of liquid stools decreased. Laboratory values were within the normal range on admission and remained unchanged. The weight increase during the first 24 hours and the reduced frequency of stools was similar in both groups.

[Radio-immunoassay method for determination of parathyroid hormone. Use of a commercially available antiserum and an international standard (author's transl)]. / Technique de dosage radioimmunologique de la parathormone humaine. Utilisation d'un antiserum disponible et d'un etalon international

A radio-immunoassay method of parathyroid hormone in peripheral circulation is described utilizing both commercially available antibody and bovine PTH preparation for iodination. As a standard, the bovine PTH delivered from the Medical Research Council (MRC) is used. Antibody-bound hormone is separated from free hormone by solid phase immunoprecipitation. Good cross reactivity of this antiserum to human PTH is shown, but because of the lack of human standard, it is demonstrated, that results may be expressed in reference to the MRC bovine hormone. The coefficient of interassay variation is 12% and the detection limit is 300 pg/ml. In every healthy subject, immunoreactive PTH is detected: the normal distribution range (n equals 31) was 400 to 1800 pg/ml. Two hypoparathyroid patients have undetectable levels. There is a slight overlap between normal and those from hyperparathyroid patients. The present method gives results expressed in international units (MRC standard). The reliability of the PTH radio-immunoassay is dependent on the characteristics of the antiserum. This method provides a basis for the establishment of PTH values with the possibility of comparing results in health and disease.

[Circulating calcitonin in fulminating purpura in children]. / Calcitonine circulante au cours du purpura fulminans de l'enfant.

Hypocalcaemia may complicate the treatment of fulminating meningococcaemia in children. In an attempt to elucidate the pathophysiology of the hypocalcaemia, we have measured accompanying changes in blood levels of calcitonin (BW-336-6 antiserum) and parathyroid hormone (C-terminal antiserum IRE). Ten children aged 1-11 years with fulminating meningococcaemia are studied. The high PTH levels may be a response to the hypocalcaemia, but the hypercalcitoninaemia seems inappropriate. Provided the immunoreactivity of the calcitonin detected corresponds to calcitonin 1-32, the origin of this hypercalcitoninaemia remains to be explained.

Siblings of sudden infant death syndrome and near miss in about 30 families: is there a genetic factor?

The purposes of this study were: (1) to compare our data with those reported in the general population; (2) to find a factor implicated in repetitive accidents; (3) to look for a possible genetic factor; and (4) to evaluate whether or not the risk of recurrence was the same in a family with two or more infants having died of sudden intant death syndrome (SIDS) as in the general population. We study retrospectively 77 files which constitute a group of 30 families which was analysed with reference to a list of data laid out in the shape of genealogical trees. Our study shows that risk factors are similar to those described previously and repetitive among siblings or cousins. The rate of recurrence is not available for the general population. On studying some family trees, we can speculate on the existence of an autosomal dominant gene with incomplete penetrance.

[Esophageal pH-metry and gastroesophageal reflux in infants and children]. / pHmétrie oesophagienne et reflux gastro-oesophagien du nourrisson et de l'enfant.

Twenty five infants, all under 3-year-old, 16 with symptoms of gastroesophageal reflux and 9 controls, were studied by continuous pH esophageal monitoring during 18 to 24 h. The diagnostic value of several pH parameters was calculated in reference to the upper limits of normal ranges previously determined in other studies performed in similarly aged children. Sensitivity and specificity of these parameters were respectively 69 and 89 p. 100 for the time elapsed below pH 4, 44 and 100 p. 100 for the number of reflux episodes per hour, 56 and 89 p. 100 for the duration of the longest episode of reflux, and 31 and 100 p. 100 for the number of reflux episodes lasting more than 5 min. These results confirm that a percentage Of reflux time (less than pH 4) longer than 5.2 p. 100 of the total duration of pH recording has the best discriminative value. However in clinical practice 2 or 3 h postprandial pH recording have a good diagnostic value when the results are expressed using a reflux score, as in adult patients. In further studies concerning gastroesophageal reflux in infants, it is concluded that diagnostic criteria must include evidence of reflux using a discriminant pH parameter.

[Hemorrhagic dengue with shock in children in French Polynesia]. / La dengue hémorragique avec choc chez l'enfant en Polynésie française.

The dengue fever is an intertropical arbovirus, well known in French Polynesia where the first cases of dengue haemorrhagic fever appeared at the end of 1989. The authors report their experience in the paediatrics ward of the Centre Hospitalier Territorial (CHT) of Papeete, where, from 1990 to 1992, 310 cases of dengue fever have been registered with 79 cases of dengue shock syndrome (25.5%) and 12 deaths (4%). Then, following an epidemiologic summary and a description of how the clinical picture evolves in children, they insist on the fact that the pathophysiology of dengue fever is unknown, and there is no predictive factor; even if, in this study, the young age seems to be factor of severity. Therefore, an epidemiologic survey, and a very close monitoring of each case are necessary, in order to start an aggressive symptomatic treatment as soon as possible. The antivector's fight is still the only prevention against this arbovirosis.