Non-classic cystic fibrosis associated with D1152H CFTR mutation.

BACKGROUND: Limited knowledge exists on phenotypes associated with the D1152H cystic fibrosis transmembrane conductance regulator (CFTR) mutation. METHODS: Subjects with a D1152H allele in trans with another CFTR mutation were identified using the French Cystic Fibrosis Registry. Phenotypic characteristics were compared with those of pancreatic insufficient (PI) and pancreatic sufficient (PS) cystic fibrosis (CF) subjects in the Registry (CF cohort). RESULTS: Forty-two subjects with D1152H alleles were identified. Features leading to diagnosis included chronic sinopulmonary disease (n = 25), congenital absence of the vas deferens (n = 11), systematic neonatal screening (n = 4), and genetic counseling (n = 2). Median age at diagnosis was 33 [interquartile range (IQR, 24-41)] years in D1152H subjects. Median sweat chloride concentrations were 43.5 (39-63) mmol/l in D1152H subjects and were markedly lower than in PI and PS CF subjects (p < 0.05). Bronchiectasis was present in 67% of D1152H subjects, but Pseudomonas aeruginosa colonization and pancreatic insufficiency were present in <30% of subjects. Estimated rates of decline in forced expiratory volume in 1 s (FEV(1)) were lower in D1152H subjects vs PI CF subjects (p < 0.05). None of the D1152H subjects identified since 1999 had died or required lung transplantation. CONCLUSIONS: When present in trans with a CF-causing mutation, D1152H causes significant pulmonary disease, but all subjects had prolonged survival.

[Prevalence of teenage sleeping disorders]. / Troubles du sommeil chez les lycéens : prévalence et facteurs associés.

Teenage sleeping disorders can have short- and long-term consequences such as learning disorders, accidents, depression, and type 2 diabetes. OBJECTIVE: To assess the prevalence of sleeping disorders in high school students in the southwest of Brittany (Finistère), France. To search for family and social factors causing these disorders and drug use. METHOD: Observational multicenter study that took place in May, 2015, asking high school students to anonymously complete a questionnaire during school time. A variable was created: sleep disorders (TrS+) when teenagers responded "often" or "very often" to at least one of the six questions concerning sleeping disorders. RESULTS: The prevalence of TrS+ was 73 % (4170/5556). These teenagers had difficulty falling asleep (36 %), woke up during the night (33 %), or had nightmares (10 %). Their sleep routine was disrupted (35 %), they did not feel rested the following day (49 %): 9 % were late for class related to their sleeping disorders. TrS+ were more recurrent among females (OR: 2.64; P<0.0001). A negative atmosphere in high school (OR: 2.64; P<0.0001), tobacco use (>10 cigarettes per a day) (OR: 2.39; P<0.0001), alcohol (OR: 1.4, P=0.009), marijuana (<1 time per day; OR: 2.05; P=0.009), and time spent using a computer or watching television (>8h per a day; OR: 2.7; P<0.0001) had an impact on their sleep quality. Ten percent of TrS+ individuals consume medications and 9 % cannabis to help them fall asleep. CONCLUSION: Technology, drugs, and well-being at school have an impact on sleep quality. Screening of teenagers with sleeping disorders and information programs for teenagers must be provided by the teaching and medical staff.

[Acute leukemia revealed by bone magnetic resonance imaging: Two pediatric case reports]. / Leucémie aiguë découverte par imagerie par résonance magnétique osseuse : deux observations pédiatriques.

Bone and joint pain are common causes of pediatric consultation for a variety of etiologies. The causes are mostly traumatic or infectious or have an inflammatory origin. Acute leukemia (AL) can sometimes begin with osteoarticular signs and radiological investigations such as magnetic resonance imaging (MRI) can help guide the diagnosis. We report on two cases of pediatric AL revealed by osteoarticular signs, with MRI helpful in the diagnostic procedure. In these children, the first signs were recurrent joint pain, with no blood count anomalies. There was a delay between the onset of arthralgia and diagnosis due to atypical presentation of the disease. MRI guided the investigations to the diagnosis of AL. The persistence of pain or inflammation must lead to considering a bone MRI and a complete blood count must be repeated in case of persistent inflammatory bone pain to avoid a missed diagnosis of blood disease.

[Pyomyositis in children: Two cases of Staphylococcus aureus infection]. / Pyomyosite de l'enfant : deux cas d'infection à Staphylococcus aureus.

Pyomyositis is a term used to denote primary pyogenic infection of a skeletal muscle. It is a rare disease that was first described in immunodeficient patients living in tropical climates. Lately, however, cases involving healthy children have been described in temperate climates. The origin of primary pyomyositis remains unclear, although it is thought to be caused by seeding from transient bacteremia. Onset of disease is insidious, therefore necessitating rapid diagnosis to successfully select appropriate antibiotic therapy and avoid complications. The signs and symptoms of pyomyositis are nonspecific, which highlights the importance of maintaining a broad differential diagnosis including disease entities such as osteomyelitis and septic arthritis. Magnetic resonance imaging is considered the best imaging modality for distinguishing pyomyositis from other potential etiologies. Here, we present two cases of primary pyomyositis of the lower limb muscles in an 8-year-old boy and in an 11-year-old girl.

The use of poly(ethylene glycol) hydrogels to investigate the impact of ECM chemistry and mechanics on smooth muscle cells.

Hydrogels based on poly(ethylene glycol) (PEG) are of increasing interest for regenerative medicine applications and are ideal materials to direct cell function due to the ability to confer key functionalities of native extracellular matrix (ECM) on PEG's otherwise inert backbone. Given extensive recent evidence that ECM compliance influences a variety of cell functions, PEG-based hydrogels are also attractive due to the ease with which their mechanical properties can be controlled. In these studies, we exploited the chemical and mechanical tunability of PEG-based gels to study the impact of ECM chemistry and mechanics on smooth muscle cells (SMCs) in both 2-D and 3-D model systems. First, by controlling the extent of crosslinking and therefore the mechanical properties of PEG-based hydrogels (tensile moduli from 13.7 to 423.9kPa), we report here that the assembly of F-actin stress fibers and focal adhesions, indicative of the state of actin contractility, were influenced by the compliance of 2-D PEG gels functionalized with either short adhesive peptides or full-length ECM proteins. Varying ECM ligand density and identity independent of gel compliance affected the physical properties of the focal adhesions, and also influenced SMC spreading in 2-D. Furthermore, SMCs proliferated to a greater extent as gel stiffness was increased. In contrast, the degree of SMC differentiation, which was qualitatively assessed by the extent of smooth muscle alpha-actin bundling and the association of calponin and caldesmon with the alpha-actin fibrils, was found to decrease with substrate stiffness in 2-D cultures. In 3-D, despite the fact that their viability and degree of spreading were greatly reduced, SMCs did express some contractile markers indicative of their differentiated phenotype when cultured within PEG-RGDS constructs. Combined, these data suggest that the mechanical and chemical properties of PEG hydrogels can be tuned to influence SMC phenotype in both 2-D and 3-D.

Effect of estradiol on the ultrastructure of the MCF7 human breast cancer cells in culture.

We have analyzed the effect of estradiol and of two classes of antiestrogens on the morphology of the MCF7 human breast cancer cell line by scanning and transmission electron microscopy. Estradiol progressively increased the number and the length of microvilli at the cell surface. The density of the microvilli network increased between 2 and 11 days of estrogen treatment, while the cells became more granular and less tightly attached to the surface of the dish. Estradiol also progressively transformed cells into secretory cells containing, at Day 2, large, clear mitochondria and, at Day 4, rough endoplasmic reticulum and Golgi complex. At Day 6, secretory granules (diameter, 0.2 microM), which mainly contained glycoproteins, were first developed in the cytoplasm. By Day 8, they were concentrated at the cell membrane and being liberated into the medium. Larger granules (diameter, 0.8 microM), which probably contained lipids, were obtained later (Day 11). Cell cultures in 10% fetal calf serum not treated by charcoal contained secretory granules. The modifications were induced by physiological concentrations of estradiol but not 5 alpha-dihydrotestosterone. Progesterone (10 nM for 8 days) completely inhibited the effect of estradiol on the microvilli and secretory activity. Tamoxifen or hydroxy-tamoxifen did not induce secretory activity but did alter the cell morphology compared to control cells. The effects of estradiol were observed in other estrogen receptor-positive breast cancer cell lines (ZR 75-1, T 47 D) but not in an estrogen receptor-negative cell line (BT 20). This morphological evidence that estrogens modify the cell surface of breast cancer cells in culture and transform them into "secretory cells" complements evidence that a molecular weight of approximately 50,000 into the culture medium (Cell, 24: 352-362, 1980). (The molecular weight was found first to be 46,000. It seems to be closer to 52,000 in a 10% polyacrylamide gel and by using the NEN-labeled proteins as molecular weight markers.

[Testicular mass in a teenager: a case report of embryonic carcinoma discovered late]. / Masse testiculaire de l'adolescent : à propos d'un cas de carcinome embryonnaire de découverte tardive.

Testicular cancer is a rare disease in adolescents but is the leading cause of solid cancer in 15- to 30-year-old men. We report a clinical case of a 16-year-old who presented to the pediatric emergency unit with a testicular mass that had been enlarging for several months and the diagnosis turned out to be multimetastatic testicular cancer. However, early diagnosis largely determines the prognosis of this disease. A literature review enabled us to update the prognostic factors, the reasons for diagnostic delay, and current screening practices for this disease. There are currently no formal guidelines in France.

[Adolescents in the Pediatric Emergency Department: Detection of risk behavior and depression]. / Repérage des conduites à risque et des symptômes dépressifs chez les adolescents admis en service d'accueil des urgences.

OBJECTIVES: The main objective of this study was to estimate the prevalence of social and psychological problems, risk behaviors, and depression symptoms in a population of adolescents consulting in a Pediatric Emergency Department of a general hospital, and compare these according to the reasons for consulting. METHODS: Observational monocentric study, in the Pediatric Emergency Department of a general hospital in Britany, France, between January and September 2013, using a questionnaire dispensed to 12- to 18-year-old adolescents. The questions covered habits, school, symptoms, risk behaviors, and depression symptoms. Patients were classified into three groups based of the initial aim of the consultation: medical, traumatologic, and acute psychiatric. RESULTS: A total of 379 adolescents, median age: 15 years, were included. Adolescents from the "psychiatric" group resided significantly more often with only one of their parents or in a residential home; they were more often followed by an youth worker and/or a mental health professional such as a psychologist or a psychiatrist; consumed alcohol, cannabis, and/or tobacco more often; they complained more often of headache or abdominal and lumbar pain, dizziness, and sleep disorders; they consumed anxiolytic and hypnotic drugs more often; they ran away more often; and had signs of depression and/or suicidal ideation and behaviors. The prevalence of all these psychosocial and behavioral risks was also high in the two other groups. CONCLUSION: The Pediatric Emergency Department is a good place to detect adolescents with behavioral problems and/or depression symptoms, even if this is not the initial purpose of admission.

Nutritional status of children with acute lymphoblastic leukemia: a longitudinal study.

To evaluate the nutritional consequences of acute lymphoblastic leukemia and its treatment, 15 children with leukemia were studied. Anthropometric data, fat-free mass by impedance, energy intake, and resting energy expenditure (REE) were determined at diagnosis and on days 22, 36, and 71 of the treatment. Interleukin (IL)-1 beta, IL-6, interferon-gamma, and tumor necrosis factor were also measured. Fifteen healthy control subjects were matched for age and sex. Body weight and height and body composition were comparable at all times of the study, although three children were underweight at diagnosis (weight-for-height < 85% of French standards). Although two different methods were used for dietary recall in the two groups, energy intake expressed as a percentage of normal recommended values for age and sex was lower in patients than in control subjects (104 +/- 19%) on day 1 (47 +/- 32.1%) and day 22 (58 +/- 24%), but was comparable on day 36 (85 +/- 71%) and day 71 (85 +/- 48%). This low energy intake involved both carbohydrates and fats. Energy and carbohydrate intakes improved significantly during the study in patients. The nonprotein respiratory quotient (RQ) in patients was significantly lower than in control subjects (0.84 +/- 0.04) on day 1 (0.79 +/- 0.02) but was comparable on day 71. The REE of the patients on day 1 (5057.8 +/- 1588.4 kJ/24 h) and day 71 (4844.7 +/- 116.1 kJ/24 h) and of the control subjects (4313.8 +/- 823.5 kJ/24 h) was not significantly different. Cytokines remained undetectable on days 1, 36, and 71. The results showed that at the time of diagnosis and during this period of chemotherapy there was no evidence of raised REE. The poor intakes during the first month of chemotherapy were recent as shown by the parents' questionnaire responses and the absence of consequences in body composition. The transient decrease in RQ seemed to be an adaptative mechanism to the poor carbohydrate intake. No indication of undernutrition in the patients as a group was evident during the first 71 d of treatment although further long-term nutritional assessment is needed.

Differential effects of amiodarone and propranolol on lipid dynamics and enzymatic activities in cardiac sarcolemmal membranes.

The amphiphilic cationic cardioactive drugs (pindolol, propranolol and amiodarone) were tested for their effects on lipid dynamics (measured by fluorescence depolarization) and on enzymatic activities up to 1 mM in purified cardiac sarcolemmal vesicles from adult rat. The vesicles were enriched 12- to 37-fold (with respect to tissue homogenate) in Na+/K+ ATPase, K+-stimulated p-nitrophenylphosphatase, 5'nucleotidase and adenylate cyclase, all of which are believed to be components of sarcolemma. Phospholipids and cholesterol content were enriched 5- and 13-fold respectively. There was very little contamination of the sarcolemmal vesicles by sarcoplasmic reticulum (as judged by Ca2+ ATPase and glucose-6-phosphatase activities) or mitochondria (as judged by cytochrome-c-oxidase activity). Pindolol had no effect on lipid dynamics and enzyme activities except for the isoproterenol-stimulated adenylate cyclase. The latter was also totally inhibited at 1 microM by propranolol which inhibited Mg2+ ATPase and increased fluidity above 20 microM. Amiodarone affected all the enzyme activities (except Na+/K+ ATPase): isoproterenol-stimulated adenylate (IC50 = 30 microM), Mg2+ ATPase (IC50 = 20 microM) and K+-stimulated-p-nitrophenylphosphatase were inhibited; 5'nucleotidase was activated above 2 microM. By contrast with propranolol, amiodarone decreased lipid mobility. The effect was linear with the concentration of the drug above 1 microM.

Early effect of estrogen on chromatin ultrastructure in endometrial nuclei.

The effect of estradiol on chromatin ultrastructure in interphase nuclei was studied in immature rat and lamb endometrium. Physiological doses of estradiol within the first hour transformed the condensed chromatin into dispersed chromatin both in vivo and in vitro. These ultrastructural modifications were specifically induced by hormones translocating the estrogen receptor to the nucleus of estrogen-responsive tissues. Conversely, the antiestrogen tamoxifen gave a hypercondensation of chromatin. The addition of actinomycin D, cordycepin or alpha-amanitin, but not of cycloheximide, prevented the effect of estradiol both on the ultrastructural change and on [3H]uridine incorporation, suggesting that chromatin decondensation was closely related to transcriptional activity. These results indicate that in endometrium, estrogen rapidly provokes a large and extended modification of chromatin ultrastructure, which suggest a general effect on chromatin function rather than a selective activation of a limited number of genes.

Nuclear translocation of the estradiol receptor: partial inhibition by ethidium bromide.

Ethidium bromide (EB), an intercalating drug, has been shown to prevent the in vitro interaction of the estrogen receptor (R) with DNA (André et al., 1976). We have now studied the effect of this drug on the nuclear translocation of R in order to determine whether DNA integrity is needed for this translocation. In a cell-free reconstituted system made of purified nuclei and cytosol, the pretreatment of nuclei by EB prevented approximately half of the R nuclear translocation, but was unable to extract more than 17% of the E2-R previously translocated. A series of indirect evidences suggests that EB inhibits the nuclear translocation of R by interacting with nuclear DNA. The degree of the inhibition was related to the amount of drug bound to nuclei and was in agreement with the degree of ultrastructural modifications of chromatin. R was not irreversibly altered by the drug. The EB inhibition was only observed with DNA-containing particles and with estrogen receptor able to bind to DNA. In surviving uteri the drug also inhibited the R nuclear translocation. These resuts indicate two types of nuclear translocation of R, one sensitive and the other resistant to EB, and suggest that DNA is required for the EB-sensitive translocation.

Somatostatin treatment of psoriasis.

Somatostatin treatment was administered to 20 psoriatic patients according to the following protocol: Continuous infusion (250 micrograms/h) for at least 2 days followed either by short infusions (1 h) at 8 A.M. and 8 P.M. (12 cases) or by repeating the initial 2-day infusion (eight patients). Before treatment (day 0) and on day 6, biopsy specimens were taken for routine examination (12 patients) and for ultrastructure (seven patients). In vitro immunological studies were carried out on peripheral blood lymphocytes (six patients) on day 0 and day 8. In two patients, somatostatin was stopped because of serious side effects. Thus, clinical results were evaluated in 18 patients, on day 30. In ten of them no improvement whatsoever occurred, two had a partial clearing and an almost complete remission was achieved in six others. Ultrastructural studies showed, on day 6, enlargement of the intercellular spaces with deposits of granular material of glucidic composition, associated with features of cellular damage. Percentages of T and B cells were unmodified but a significant depression of mitogenic stimulation by PHA and ConA was clearly observed on day 8. Even if somatostatin treatment may have a beneficial effect in some patients it seems much less valid than other well-known therapies for psoriasis.

[Biliary atresia in French Polynesia. Retrospective study of 10 years]. / L'atrésie des voies biliaires en Polynésie française. Etude rétrospective sur 10 ans.

BACKGROUND: French Polynesia includes several ethnic groups; thus, it is well suited for evaluation of racial incidence of extrahepatic biliary atresia (BA). On the other hand, its geographic localization, far from specialized centers, does not facilitate early referral, indispensable for effective surgery. POPULATION AND METHODS: The files of 17 infants with BA, born in French Polynesia between 1 December 1981 and 1 December 1991, were retrospectively studied. During this period, there were 53,111 live births. RESULTS: The incidence of BA was 1/3,124. There were eight boys and nine girls; all belonged to the Maohi ethnic group (67% of the total population). They were admitted at the mean age of 71 +/- 33 days (range: 15-120 days); 15 of them were transferred to France at a mean age of 80 +/- 38 days (range: 35-150 days) and were operated on at 99 +/- 43 days (range: 48-195 days). The Kasai procedure was effective in four patients, with a follow-up ranging from 7 to 10 years. Among the 11 other patients, two underwent liver transplantation, four are waiting for transplantation and four have died. CONCLUSIONS: The influence of race on the incidence of BA has not been statistically established here even though this incidence appears high in French Polynesia and similar to Chinese babies in Hawaii. Local geographic conditions explain late admission in pediatric Units whereas possibilities for early surgery are improving.

[Treatment with hydroxyurea of polycythemia vera in a 11 year-old child]. / Traitement par hydroxyurée d'une polyglobulie primitive chez un enfant de 11 ans.

BACKGROUND: Polycythemia vera is a very rare disease in childhood; its treatment for this reason is not well established. CASE REPORT: An 11-year-old boy was admitted for polycythemia vera. The three classical major criteria for this condition were present and no cause for secondary polyglobulia could be recognized. The patient was given hydroxyurea. Three years later, he is well with hematocrit below 50%. CONCLUSIONS: Oral continuous myelosuppressive therapy with hydroxyurea may be proposed in children if there is no HLA-matched family member. Long-term follow-up is nevertheless necessary in order to detect relapse or side-effects of the treatment.

[Vertebral compression revealing acute lymphoblastic leukemia]. / Tassements vertébraux révélateurs de leucémie aiguë lymphoblastique.

BACKGROUND: Vertebral compression is rarely the first manifestation of acute leukemia (AL) in children. CASE REPORT: Three children, 13, 4 and 13 years of age respectively, suffered from recent and persistent back pain. The first patient was considered as having psychosomatic problems despite thrombocytopenia at the first examination. The second patient was also pale with hematoma on his legs so that AL could be rapidly recognised. An initial diagnosis of Scheuermann disease was proposed for the third patient in whom hemogram was performed due to worsening of his general condition. The three patients had extended vertebral demineralisation on the first X-rays. CONCLUSION: Causes of back pain in children are often organic at this age of life. They must be searched by suitable examinations.

[Frequency of gastroesophageal reflux in infants and in young children with cystic fibrosis]. / Fréquence du reflux gastrooesophagien chez le nourrisson et le jeune enfant atteints de mucoviscidose.

BACKGROUND: Gastro-esophageal reflux (GER) is common in chronic bronchopulmonary diseases, and may aggravate them. The aim of this study was to study frequency and characteristics of GER in infants and toddlers with cystic fibrosis (CF). POPULATION AND METHODS: Twenty-five CF patients, 45 to 954 days-old (mean 219 days) without clinical evidence of bronchopulmonary infection, were studied by prolonged pHmetry (19.45 +/- 1.89 hours). Their pulmonary state was evaluated by the number of previous courses of antibiotic treatment and analysis of the X-rays. RESULTS: Nineteen children had GER (76%); four of them had no clinical sign of GER. All 19 patients had mild or moderate signs of pulmonary impairment. The reflux index (percentage of time with pH < 4) was 12.82%. The GER episodes were more frequent during walking time (p < 0.001), but longer during sleeping time (p < 0.001). CONCLUSIONS: GER is frequent in CF patients, even the youngest. It seems primary, and not related to pulmonary impairment. Its frequency and its potential severity lead to suggesting a pHmetry to every new CF patient.

[Utilization of an equimolar mixture of oxygen-nitrous oxide in a general pediatric ward]. / Utilisation du mélange équimolaire oxygène-protoxyde d'azote dans un service de pédiatrie générale.

UNLABELLED: We report our experience of the utilization of the 50% oxygen-nitrous oxide mixture (nitrous oxide 50%) in our general pediatric ward after one year of use. PATIENTS AND METHODS: Between 1st April 1997 and 31st March 1998, children who had to undergo a painful procedure were proposed to inhale 50% nitrous oxide before the procedure. We evaluate pain, restlessness and adverse effects. RESULTS: The procedures (127 of them) were carried out in 90 children (61 boys). They were aged from 5 months to 15 years (mean: 5.7 years; median: 4.1 years). Indications were: lumbar puncture (n = 45), burning dressing (n = 29), venous cannulation (n = 12), minor surgery (n = 27), and miscellaneous (n = 14). Inhalation time was between 2 to 70 min (mean: 14.4 min; median: 11 min). Pain was absent or low in 106 cases (83.4%). Restlessness was absent or low in 100 cases (78.8%). Averse events were observed 12 times, but they were always minor and quickly reversible. CONCLUSION: Nitrous oxide (50%) can be used successfully in a general pediatric ward. Other studies are necessary to define the best conditions.

[Terminolateral portacaval shunt does not prevent hepatic regeneration after 65% hepatectomy in the dog. Value of parenteral nutritional support]. / Le shunt porto-cave termino-latéral n'empêche pas la régénération hépatique après hépatectomie de 65% chez le chien. Intérêt du support nutritionnel parentéral.

Lack of portal blood supply to the liver induced by end to side porto-caval shunt leads to liver atrophy but does not prevent hepatic regeneration after 65% hepatectomy in the dog. This work demonstrates the usefulness of parenteral nutritive support with a branched-chain amino acids enriched essential amino-acids solution in helping hepatic function restoration by comparison of three groups of animals which were fed either parenterally (two groups) or per os (1 group).