PubMed Health⌕ Search

Biomedical subjects

L Michaud

Publications and source records attributed to L Michaud.

At least 73 records · Page 4Linked to original sources
PubMed1998

Molecular mechanism of lysosomal sialidase deficiency in galactosialidosis involves its rapid degradation.

Galactosialidosis is an inherited lysosomal storage disease caused by the combined deficiency of lysosomal sialidase and beta-galactosidase secondary to the deficiency of cathepsin A/protective protein, which is associated with sialidase and beta-galactosidase in a high-molecular weight (1.27MDa) complex. Clinical phenotypes of patients as well as the composition of compounds which are stored in patient's tissues implicate sialidase deficiency as the underlying pathogenic defect. The recent cloning and sequencing of lysosomal sialidase [Pshezhetsky, Richard, Michaud, Igdoura, Wang, Elsliger, Qu, Leclerc, Gravel, Dallaire and Potier (1997), Nature Genet. 15, 316-320] allowed us to study the molecular mechanism of sialidase deficiency in galactosialidosis. By Western blotting, using antibodies against the recombinant human enzyme, and by NH2-terminal sequencing, we showed that sialidase is synthesized as a 45.5 kDa precursor and after the cleavage of the 47-amino acid signal peptide and glycosylation becomes a 48.3 kDa mature active enzyme present in the 1.27 kDa complex. Transgenic expression of sialidase in cultured skin fibroblasts from normal controls and from galactosialidosis patients, followed by immunofluorescent and immunoelectron microscopy showed that in both normal and affected cells the expressed sialidase was localized on lysosomal and plasma membranes, but the amount of sialidase found in galactosialidosis cells was approximately 5-fold reduced. Metabolic labelling studies demonstrated that the 48.3 kDa mature active form of sialidase was stable in normal fibroblasts (half-life approximately 2.7 h), whereas in galactosialidosis fibroblasts the enzyme was rapidly converted (half-life approximately 30 min) into 38.7 and 24 kDa catalytically inactive forms. Altogether our data provide evidence that the molecular mechanism of sialidase deficiency in galactosialidosis is associated with abnormal proteolytic cleavage and fast degradation.

Animals↗
PubMed1998

[Effect of rhDNase on the respiratory function and nutritional status of children and adolescents with mucoviscidosis].

BACKGROUND: In 1994 we started recombinant human deoxyribonuclease (rhDNase) in every cystic fibrosis (CF) patient whatever his (her) clinical condition, provided they were aged more than 5 years and forced vital capacity (FVC) was > or = 40%. POPULATION AND METHODS: We reviewed retrospectively the effects of rhDNase in 69 CF children and adolescents during a 2-year follow-up. Patients (35 boys, 34 girls) received 2.5 mg of rhDNase once daily from a mean age of 8.5 years (range 5-16.4). Baseline spirometric values (% predicted) and nutritional status were as followed: FVC = 84.8 +/- 21.7; forced expiratory volume in 1 second (FEV1) = 80.8 +/- 22.2; peak flow = 89.7 +/- 34.2, forced expiratory fraction 25-75% (FEF 25-75) = 71.8 +/- 32.8; Z score weight/height = -0.41 +/- 1.14; Z score weight/age = -0.48 +/- 1.25, body mass index = 15.4 +/- 1.8; caloric intake = 107 +/- 25% of recommended dietary allowances (RDA). Patients had a Shwachman-Kulczycki's score of 87 +/- 9. Spirometric and nutritional data were analysed after 1, 3, 6, 12, 18 and 24 months of treatment and compared to baseline values (changes evaluated as percent change from mean baseline for spirometric data). Shwachman-Kulczycki's score was calculated after 24 months of rhDNase. RESULTS: An improvement of FVC (+10.7%, P < 0.001) and FEV1 (+12%, P < 0.01) was noted after one month of treatment and was maintained throughout the following 2 years around 8.7% (6.4-11.4) for FVC and 8.2% (7.3-9.1) for FEV1, P < or = 0.01. This was particularly observed in children aged 5 to 10 years, in boys and in patients with a baseline FVC under 70% predicted. There was no significant change in FEF 25-75. We observed an improvement of daily caloric intake from the third month (P < 0.05) and of body mass index from the sixth month (P = 0.02). This was particularly noted in girls. Z score weight/age was improved only during the first 3 months of treatment while Z score weight/height increased only after a 2 year follow-up. There was no significant change in Shwachman-Kulczycki's score after 24 months of rhDNase. CONCLUSION: rhDNase in CF children in effective on lung function as well as on nutritional status and the response to this treatment can be evaluated after the first 3 months.

Adolescent↗
PubMed1998

[Long-term follow-up of children with esophageal caustic stenosis].

BACKGROUND: Long term follow-up of children with esophageal caustic stenosis is not well known. The aim of the present study was to describe functional, organic and psychological, as well as social consequences. PATIENTS AND METHODS: Thirty-four children with a mean age of 3 years and 7 months +/- 3 years and 2 months (ranges: 1 month-14 years and 3 months) were included in a longitudinal study. Various parameters have been studied: treatment, functional symptoms, nutritional status (weight/height, body composition) and psychological and social consequences. chi 2 and Mann-Whitney tests were used for statistical analysis. RESULTS: Twenty-one patients have been treated by mechanical dilatations whereas surgery was performed in 12 children; the mean number of dilatations per child was higher in patients treated by dilatations (21 +/- 17 vs 14 +/- 16; P < 0.05). The frequency of dysphagia was not different in patients with colon interposition or not (69% vs 53%; P = 0.1). Nutritional status was not affected by the presence of esophageal caustic stenosis. Psychological and social consequences were characterized by scholastic difficulties, anxiety and severe depression. One case of suicide was observed. CONCLUSION: Children with caustic stenosis should be followed for a long period of time. A multidisciplinary approach is necessary, taking into account medical, social and psychological consequences.

Adolescent↗
PubMed1998

[Children who swallow air].

UNLABELLED: Gas in the gut derives from swallowed air, intra-luminal production and diffusion from the blood. Excessive swallowed air may cause pathologic aerophagy. CASE REPORTS: This report describes four children aged from 3 to 12 years with pathologic aerophagy due to excessive air swallowing. One of them had a "Gas Bloat Syndrome". Clinical presentation was very incongruous. However, the clinical features were characteristic: abdominal distention increasing throughout the day, associated with visible and often audible air swallowing and excessive flatus. The questioning and clinical examination helped for diagnosing. Medical symptomatic treatment was associated with a psychotherapy approach. CONCLUSION: A better recognition of this condition might contribute towards earlier diagnosis.

Adolescent↗
PubMed1998

Cystic fibrosis: nutritional consequences and management.

Malnutrition is an adverse prognostic factor in cystic fibrosis, influencing the course of pulmonary disease and correlating inversely with survival. A positive energy balance between energy intake and the combination of total energy expenditure, energy losses and growth-related energy cost is essential to maintain normal nutritional status. Before starting nutritional supplementation, it is important to rule out pathological conditions that may have a deleterious effect on nutritional status: persistent exocrine pancreatic insufficiency, chronic bacterial pulmonary colonization, impaired glucose tolerance, specific nutritional deficits and associated disorders leading to a decrease of energy intake. Several methods are available, ranging from boosted oral nutrition to behavioural intervention, oral supplementation, enteral nutrition and, rarely, parenteral nutrition. The use of elemental nutrients for either oral supplementation or enteral nutrition seems of no nutritional benefit and is more expensive than conventional polymeric nutrients. Provided that the goals of the nutritional supplementation are fulfilled, simpler is often better.

Adolescent↗
PubMed1998

Comparing the extent of protein build-up on several disposable lenses by two spectrophotometric methods.

This study aims to quantify levels of protein build-up on high-water ionic (Type IV) disposable contact lenses worn by patients, by two spectrophotometric methods, previously validated only with conventional lenses. Forty lenses were analyzed and the related results were compared. The Ninhydrine-Lysozyme method and the Coomassie Blue Albumin one agreed in identifying the most spoiled lenses. Etafilcon A attracted significantly more protein than the other materials tested, which were in the following decreasing order of protein spoilation: Ocuflcon D, Ocufilcon A and Vasurfilcon A. These similar findings suggest that it is possible to use the above mentioned analysis methods for an accurate evaluation of the contamination of several materials of disposable/frequent replacement lenses as for conventional lenses.

Journal Article↗
PubMed1998

Congenital hepatic fibrosis: findings at MR cholangiopancreatography.

OBJECTIVE: This study describes the MR imaging features of congenital hepatic fibrosis in four children who were examined with MR cholangiopancreatography. CONCLUSION: MR cholangiopancreatography effectively reveals biliary cysts, dilatation of intrahepatic bile ducts, and polycystic kidney disease, findings often associated with congenital hepatic fibrosis. This diagnosis should be suspected when these biliary and renal abnormalities are associated with hepatosplenomegaly in a patient with normal liver function.

Adolescent↗
PubMed1998

[Trichobezoars in children and adolescents].

BACKGROUND: Trichobezoars are composed of hair or fibres. The typical patient presenting with a trichobezoar is an adolescent girl experiencing mental disturbance or retardation. CASE REPORT: Three girls with trichobezoars were seen. Two of them, 4 and 15 years old, had serious digestive antecedents (corrosive oesophagogastritis and oesophageal atresia, respectively) and had undergone previous surgery. The third was a 13-year-old mentally retarded girl. In two cases, an enzymatic dissolution trial was unsuccessful, requiring secondary surgical removal after, in one case, ineffective gastroscopic removal complicated by an oesophageal perforation. The third child had an initial operative removal. DISCUSSION: Serious digestive antecedents may favour bezoars, a diagnosis that must be evoked in such patients presenting with chronic digestive symptoms. Enzymatic dissolution is ineffective for large bezoars, and gastroscopic removal carries some risks such as perforation or intestinal obstruction. Operative removal is usually indicated. Psychiatric follow-up is needed to prevent this complication in children with serious digestive antecedents and to reduce the risk of recurrences.

Adolescent↗
PubMed1997

[Small intestine atresia and abnormal insertion of the umbilicus in a child with fetal alcohol syndrome].

BACKGROUND: Fetal alcohol syndrome is quite common in our region (incidence: 1/700 live births). It usually associates facial dysmorphism, intra-uterine growth retardation and mental delay. CASE REPORT: Jonathan, born to an alcoholic mother, presented a typical dysmorphy of fetal alcohol syndrome and a low inserted umbilicus. A small bowel atresia was discovered at the third day of life and operated on. CONCLUSION: Although never been previously described, this association suggests a common embryological origin between fetal alcohol syndrome, small bowel atresia, and umbilical abnormality.

Female↗
PubMed1997

[Autoimmune hepatitis treated with cyclosporin revealed by acute hepatocellular failure].

BACKGROUND: Autoimmune hepatitis (AIH), usually chronic hepatitis, can be revealed by an acute episode of hepatic failure not easily treatable. CASE REPORT: A 4 year-old boy presented with severe acute hepatic failure (AHF) without hypergammaglobulinemia, revealing AIH. A triple immunosuppressive treatment (prednisolone, azathioprine, ciclosporine) was started when clinical and biological signs worsened (prothrombin time 18%, factor V 32%). Liver functions significantly improved within 10 days, although complications due to intensive immunosuppression occurred (Candida septicemia). CONCLUSION: AIH must be evocated in each case of AHF. Some observations of AIH treated with ciclosporine are published but protocols of its administration are variable: ciclosporine is used alone or associated with other drugs, in first intention or secondarily, when the classical treatment is contra-indicated or fails. Controlled studies are needed to precise ciclosporine indications in AIH and to propose the best protocol.

Anti-Inflammatory Agents↗
PubMed1997

[Gastroesophageal reflux and esophageal motility disorders in infants with vagal hyperreflectivity presenting severe syncope].

AIM: The aim of the study was to evaluate the prevalence of gastroesophageal reflux and abnormalities of esophageal motility in a population of neonates referred for apparently life threatening event (ALTE) and presenting vagal hyperreflectivity. POPULATION AND METHODS: The study included 17 infants, who were examined after an ALTE. They were admitted at a mean age of 11.7 weeks (range 1-40 weeks). Vagal hyperreflectivity was confirmed in each infant by oculocardiac reflex. Before treatment, 24-hour intraesophageal pH-monitoring and esophageal manometry were performed. RESULTS: pH-monitoring and esophageal manometry were both normal in only two patients. pH-monitoring showed pathological reflux (% of time with pH < 4 more than 4.8%) in 10/17 (59%) patients. Manometric studies showed esophageal dysmotility in 12/17 (71%) of patients. Hypertensive lower sphincter was noted in 11/17 (65%) infants. Patients with normal manometry were older than patients presenting with esophageal dysmotility (P < 0.05). CONCLUSION: This study shows a high frequency of gastroesophageal reflux and dysmotility in infants with vagal hyperreflectivity. Hypertensive lower esophageal sphincter as well as vagal hyperreflectivity may correspond to dysmaturity of autonomous nervous system and facilitate the occurrence of ALTE.

Esophageal Motility Disorders↗
PubMed1997

[Neonatal esophago-gastro-duodenoscopy. Apropos of 123 examinations performed on 107 newborn infants].

UNLABELLED: Upper gastrointestinal endoscopy is frequently used in the neonatal period. The aim of this study was to assess the frequency of the different lesions occurring as well as to precise indications of upper gastrointestinal endoscopy in neonates. POPULATION AND METHODS: A retrospective study including 107 neonates referred between October 1986 and April 1995 has been achieved in the pediatric gastroenterology unit of the Lille University Hospital. Various factors were analysed: gestational age, sex, reasons for endoscopy and macroscopic lesions observed. Three groups were constituted according to macroscopic findings; group I: normal aspect (n = 22); group II: isolated esophagitis (n = 27); group III: esogastritis or gastroduodenitis or esogastroduodenitis (n = 38). Chi 2 test was performed for statistical analysis. RESULTS: Signs recalling esophagitis (cry during feeding) were more frequent in group II than in group III: 37% vs 13% (P < 0.03). The neonates undergoing endoscopy for life-threatening events were more frequent in group I than in group II or III, respectively: 59% vs 15% (P < 0.01) and 59% vs 8% (P < 10(-4). Upper gastrointestinal endoscopy led to a precise diagnosis in 80% of the neonates. However 95% of those examined for hematemesis presented macroscopic lesions. CONCLUSIONS: Hematemesis and suspicion of esophagitis are good indications for upper gastrointestinal endoscopy in neonatal period. In life-threatening events and suspicion of pyloric stenosis, upper gastrointestinal endoscopy is only complementary of more contributive other examinations.

Duodenoscopy↗
PubMed1997

Cloning, expression and chromosomal mapping of human lysosomal sialidase and characterization of mutations in sialidosis.

Sialidase (neuraminidase, EC 3.2.1.18) catalyses the hydrolysis of terminal sialic acid residues of glyconjugates. Sialidase has been well studied in viruses and bacteria where it destroys the sialic acid-containing receptors at the surface of host cells, and mobilizes bacterial nutrients. In mammals, three types of sialidases, lysosomal, plasma membrane and cytosolic, have been described. For lysosomal sialidase in humans, the primary genetic deficiency results in an autosomal recessive disease, sialidosis, associated with tissue accumulation and urinary excretion of sialylated oligosaccharides and glycolipids. Sialidosis includes two main clinical variants: late-onset, sialidosis type I, characterized by bilateral macular cherry-red spots and myoclonus, and infantile-onset, sialidosis type II, characterized by skeletal dysplasia, mental retardation and hepatosplenomegaly. We report the identification of human lysosomal sialidase cDNA, its cloning, sequencing and expression. Examination of six sialidosis patients revealed three mutations, one frameshift insertion and two missense. We mapped the lysosomal sialidase gene to human chromosome 6 (6p21.3), which is consistent with the previous chromosomal assignment of this gene in proximity to the HLA locus.

Amino Acid Sequence↗
PubMed1997

Normal gastric histology in Helicobacter pylori-infected children.

BACKGROUND: In adults, Helicobacter pylori infection is always associated with gastritis or ulcer. However, very active gastritis and ulcers are rarely seen in children. The aim of the present work was to study the relationships between H. pylori and gastric mucosa in children. METHODS: Eighty infected children and adolescents including 48 (60%) neurologically impaired institutionalized patients, aged 2 months-22 years (mean 11.7 +/- 5.2 years) were studied retrospectively. All the patients underwent gastroscopy, and three antral and two fundic biopsy specimens were taken for histology and bacteriology. RESULTS: A normal gastric mucosa was found in 22 of 80 patients (27.5%), whereas the others had gastritis (n = 58, 72.5%). There were no statistical differences between patients with normal histology and those presenting with gastritis for age, sex, ethnic background, symptoms, and the degree of bacterial colonization. The macroscopic aspect of gastritis was less frequently found in children with a normal histology compared with those with histological gastritis (p < 0.001). CONCLUSIONS: These data show that H. pylori infection can be associated with a normal gastric histology in children.

Adolescent↗
PubMed1996

Influence of recombinant interferon alpha on nutritional status and growth pattern in children with chronic viral hepatitis.

UNLABELLED: Anorexia and weight loss are frequently reported as adverse effects during recombinant interferon alpha (rIFN-alpha) treatment. The aim of the present study was to assess both nutritional status and growth of children and adolescents treated with rIFN-alpha for chronic viral hepatitis. Eleven patients aged 4-16 years with histologically proven chronic active hepatitis (hepatitis B, n = 9; hepatitis C, n = 2) receiving rIFN-alpha subcutaneously thrice a week for 6 months were studied. Weight and height increments were assessed during the 6 months before starting rIFN-alpha. Weight and height were measured every 3 months (M0, M3, M6) during the 6 months of rIFN-alpha treatment, then every 6 months during the follow up period (6-36 months). Weight decreased in every child during rIFN-alpha treatment (weight loss varies from 0.5 to 2.6 kg after 3 months of treatment). Weight/age Z-score decreased from 0.12 at M0 to -0.69 at M3 (P < 0.01), then increased between M3 and M6 (-0.33) (P < 0.01), but normalized (0.02) only 6 months after completion of treatment. Nutritional status was significantly impaired during treatment (Z-score for weight/height decreased from 0.18 at M0 to -0.74 at M3, P < 0.01) and recovered progressively thereafter. Height and height velocity were not modified by rIFN-alpha treatment. A reduction of the caloric intake observed between M0 and M3 might explain these features. CONCLUSION: Significant but transient abnormalities of the nutritional status are encountered constantly at the beginning of rIFN-alpha therapy without any deleterious effect on growth. Information of the families and nutritional intervention during treatment should be required, in order to limit the importance of weight loss.

Adolescent↗