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Biomedical subjects

P Richard

Publications and source records attributed to P Richard.

At least 37 records · Page 2Linked to original sources
PubMed2004

Agitation and changes of Bispectral Index and electroencephalographic-derived variables during sevoflurane induction in children: clonidine premedication reduces agitation compared with midazolam.

BACKGROUND: This double-blind randomized study was undertaken to assess agitation, Bispectral Index (BIS) and EEG changes during induction of anaesthesia with sevoflurane in children premedicated with midazolam or clonidine. METHODS: Children were allocated randomly to receive rectal midazolam 0.4 mg kg(-1) (n=20) or oral clonidine 4 microg kg(-1) (n=20) as premedication. Rapid induction of anaesthesia was achieved with inhalation of sevoflurane 8% in nitrous oxide 50%-oxygen 50%. After tracheal intubation, the children's lungs were mechanically ventilated and the inspired sevoflurane concentration was adjusted to achieve an end-tidal fraction of 2.5%. The EEG and BIS were recorded during induction until 10 min after tracheal intubation. The EEG was analysed using spectral analysis at five points: baseline, loss of eyelash reflex, 15 s before the nadir of the BIS (BIS(nadir)), when both pupils returned to the central position (immediately before intubation), and 10 min after intubation. RESULTS: Agitation was observed in 12 midazolam-treated and five clonidine-treated patients (P=0.05). At baseline, EEG rhythms were slower in the clonidine group. Induction of anaesthesia was associated with similar EEG changes in the two groups, with an increase in total spectral power and a shift towards low frequencies; these changes were maximal around the end of the second minute of induction (BIS(nadir)). When the pupils had returned to the central position, fast EEG rhythms increased and BIS was higher than BIS(nadir) (P<0.05). In both groups, agitation was associated with an increase in slow EEG rhythms at BIS(nadir). CONCLUSIONS: Compared with midazolam, clonidine premedication reduced agitation during sevoflurane induction. During induction with sevoflurane 8% (oxygen 50%-nitrous oxide 50%), the nadir of the BIS occurred at the end of the second minute of inhalation. Agitation was associated with a more pronounced slowing of the EEG rhythms at BIS(nadir) compared with inductions in which no agitation was observed. The BIS may not follow the depth of anaesthesia during sevoflurane induction in children.

Adjuvants, Anesthesia↗
PubMed2004

[Congenital myasthenic syndromes due to mutations in the rapsyn gene].

Congenital myasthenic syndromes (CMS) are genetic diseases characterized by dysfunctional neuromuscular transmission and usually start during the neonatal period. Most are due to postsynaptic abnormalities, specifically to mutations in the acetylcholine receptor (AChR) genes. In 2002, the group of A Engel reported the first cases of CMS with mutations in the gene coding rapsyn, a postsynaptic molecule which stabilizes AChR aggregates at the neuromuscular junction. Since this first publication, more than 30 other cases, including six in France, have been reported. Study of these published cases allows us to distinguish three classes of phenotypes: 1) severe neonatal cases; 2) more benign cases, starting during infancy; 3) cases with facial malformations, involving Jewish patients originating from the Near-East. Comparison of the observations of other groups with our own has led us to the following conclusions: the N88K mutation is frequent (homozygous in 50% of cases); besides the N88K mutation, the second mutation varies considerably; heterozygous allelic cases (N88K + another mutation) are severe; there is probably a founder effect in the European population. There is phenotypic variability in the homozygous N88K cases, with benign cases and severe cases of early expression. A Engel and colleagues report that the seven cases of benign CMS with facial malformation, previously described in the Jewish population of Iraq and Iran, were caused by mutation in the promoter region of the rapsyn gene.

Alleles↗
PubMed2004

Congenital myasthenic syndrome due to rapsyn deficiency: three cases with arthrogryposis and bulbar symptoms.

We report the cases of 3 children with postsynaptic congenital myasthenic syndrome with acetylcholine receptor deficiency due to rapsyn deficiency. Symptoms began at the neonatal period with hypotonia, arthrogryposis, bulbar symptoms, and respiratory distress. Two of the 3 children needed tracheostomy and gastrostomy. Electromyograms showed a decremental response to repetitive stimulation. Muscle biopsies were normal or showed type I fiber preponderance. Genetic studies identified mutations in the rapsyn gene (RAPSN). The 3 patients were heterozygous for N88 K and a second mutation (either Y86X, 1083_1084 dupCT or IVS4-2 A > G). The patients responded favorably to anticholinesterase treatment, with a clear improvement of clinical symptoms, especially the bulbar symptoms of apneas and swallowing disturbances. This paper underlines the importance of anticholinesterase medication in patients with congenital myasthenic syndrome due to rapsyn deficiency.

Adult↗
PubMed2004

Postprandial metabolic profiles following meals and snacks eaten during simulated night and day shift work.

Shift workers are known to have an increased risk of developing cardiovascular disease (CVD) compared with day workers. An important factor contributing to this increased risk could be the increased incidence of postprandial metabolic risk factors for CVD among shift workers, as a consequence of the maladaptation of endogenous circadian rhythms to abrupt changes in shift times. We have previously shown that both simulated and real shift workers showed relatively impaired glucose and lipid tolerance if a single test meal was consumed between 00:00-02:00 h (night shift) compared with 12:00-14:00 h (day shift). The objective of the present study was to extend these observations to compare the cumulative metabolic effect of consecutive snacks/meals, as might normally be consumed throughout a period of night or day shift work. In a randomized crossover study, eight healthy nonobese men (20-33 yrs, BMI 20-25kg/m2) consumed a combination of two meals and a snack on two occasions following a standardized prestudy meal, simulating night and day shift working (total energy 2500 kcal: 40% fat, 50% carbohydrate, 10% protein). Meals were consumed at 01:00/ 13:00 h and 07:00/19:00h, and the snack at 04:00/16:00 h. Blood was taken after an overnight fast, and for 8 h following the first meal on each occasion, for the measurement of glucose, insulin, triacylglycerol (TAG), and nonesterified fatty acids (NEFA). RM-ANOVA (factors time and shift) showed a significant effect of shift for plasma TAG, with higher levels on simulated night compared to day shift (p < 0.05). There was a trend toward an effect of shift for plasma glucose, with higher plasma glucose at night (p = 0.08), and there was a time-shift interaction for plasma insulin levels (p < 0.01). NEFA levels were unaffected by shift. Inspection of the area under the plasma response curve (AUC) following each meal and snack revealed that the differences in lipid tolerance occurred throughout the study, with greatest differences occurring following the mid-shift snack. In contrast, glucose tolerance was relatively impaired following the first night-time meal, with no differences observed following the second meal. Plasma insulin levels were significantly lower following the first meal (p < 0.05), but significantly higher following the second meal (p < 0.01) on the simulated night shift. These findings confirm our previous observations of raised postprandial TAG and glucose at night, and show that sequential meal ingestion has a more pronounced effect on subsequent lipid than carbohydrate tolerance.

Adult↗
PubMed2004

Danon's disease as a cause of hypertrophic cardiomyopathy: a systematic survey.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease caused by mutations in sarcomeric genes. However, extensive genetic screening failed to identify a mutation in about a third of cases. One possible explanation is that other diseases, caused by other genes, may mimic HCM. OBJECTIVE: To investigate the possible involvement of Danon's disease, an X linked lysosomal disease, in a large population of patients with HCM. METHODS: A population of 197 index cases was considered; 124 were subsequently excluded because of a mutation in sarcomeric genes and 23 because of autosomal dominant inheritance. Fifty index cases were therefore included in molecular analysis (direct sequencing) of the lysosome associated membrane protein 2 (LAMP2) gene responsible for Danon's disease. RESULTS: Two new mutations leading to premature stop codons were identified in patients who evolved towards severe heart failure (< 25 years old): 657C>T and 173_179del. The prevalence was therefore 1% of the total population (two of 197) or 4% of enrolled index cases (two of 50). Interestingly, Danon's disease was responsible for half of the cases (two of four) with HCM and clinical skeletal myopathy but was not involved in isolated HCM (none of 41). CONCLUSIONS: Danon's disease may be involved in patients with previously diagnosed as HCM. A diagnosis strategy is proposed. To distinguish HCM from Danon's disease is important because the clinical evolution, prognosis, mode of inheritance, and therefore genetic counselling are very different.

Adolescent↗
PubMed2004

[Oculopharyngeal muscular dystrophy: study of patients from seven Spanish families with different GCG expansions in PABP2 gene].

INTRODUCTION: Autosomal dominant oculopharyngeal muscular dystrophy (OPMD), with late onset due to ptosis and/or dysphagia, is caused by short (GCG)8-13 triplet-repeat expansions in the polyadenylation binding protein 2 (PABP2) gene, which is localized in chromosome 14q11. The severity of the dominant OPMD as well as the number of expansions that cause the disease are variable. (GCG)9 is mentioned as the most frequent and the genotype/phenotype has still not been well-determined. OBJECTIVE: To describe the type of expansions (GCG)n found in Spanish families with OPMD, establishing if there is variability of them and the possible geno-phenotypical correlations. METHODS: Clinicopathological and molecular studies have been performed in 15 consecutive patients, belonging to seven Spanish families with OPMD. The muscular biopsy study under electronmicroscopy shows intranuclear inclusions (INIs) in all the examined patients (one patient per family). The genetic findings confirm the cause of the disease in all the affected members and in one clinically asymptomatic member of one recently examined family: three families (six, one and one studied members, respectively) present the (GCG)9 expansion, two families (one studied member each one) present the (GCG)10 expansion and two families (one and four studied members respectively) present the (GCG)11 expansion. In these 15 patients with a short GCG expansion causing OPMD, clinical tests for OPMD and a follow-up study of their clinical course have been carefully assessed: in patients with the (GCG)9 expansion major abnormalities appeared in extrinsic ocular mobility and more precocious presentation of limb girld (lumbopelvic preferentially) weakness leading to a great disability before the seventh decade of life under the seventies in some patients and sometimes leading to death. In patients with (GCG)10 and (GCG)11 expansions, eye movements are always preserved and the limb girld muscles weakness did not appear before the seventh decade. No correlation seems to exist between age of onset of the ptosis or dysphagia and the different (GCG)n expansions and the surgical treatment of ptosis, performed in eight patients, showed good results independently of the (GCG)n mutation. CONCLUSIONS: Although further clinical and genetic studies are necessary to establish a strict genotype/phenotype correlation in OPMD, we concluded that the (GCG)9 expansion involve more severe phenotypes than those related to the (GCG)10 or (GCG)11 expansions. Therefore, genetic testing could benefit prognosis in asymptomatic individuals.

Adult↗
PubMed2003

Accuracy of European diagnostic criteria for familial hypertrophic cardiomyopathy in a genotyped population.

BACKGROUND: Since the sensitivity of conventional diagnostic criteria for familial hypertrophic cardiomyopathy (HCM) is low, new diagnostic criteria were proposed by a European collaboration. However, their diagnostic value remains unknown. The aim of the study was to evaluate the accuracy of these new criteria, using the genetic status as the criterion of reference. METHODS: We studied 109 genotyped adults (54 genetically affected, 55 unaffected) from 7 families (mutations in 3 genes). Major European echographic criteria were a maximal wall thickness >or=13 mm or >or=15 mm according to the segment involved, or the presence of SAM. Major European ECG criteria were abnormal Q waves, left ventricular hypertrophy, or marked ST-T changes. Combined major/minor European criteria were also evaluated. RESULTS: Sensitivity and specificity of major European criteria (72 and 92%, respectively) were similar to those of major conventional criteria (70 and 94%) and were not improved by combined major/minor European criteria (72 and 90%). When all the minor European criteria were considered, sensitivity increased to 87% but specificity dramatically decreased to 51%. However, one of these minor ECG criteria, deep S V2, was of interest and when added to major European criteria, sensitivity increased to 76% and specificity remained good (90%). CONCLUSIONS: The diagnostic value of new European criteria for HCM was evaluated for the first time. We found that it was not different from that of conventional criteria, with a good specificity but a low sensitivity. Additional criteria should be studied to improve the early identification of HCM.

Adult↗
PubMed2002

Lamin A/C mutations with lipodystrophy, cardiac abnormalities, and muscular dystrophy.

Mutations in the lamin A/C gene are found in Emery-Dreifuss muscular dystrophy, limb girdle muscular dystrophy with cardiac conduction disturbances, dilated cardiomyopathy with conduction system disease, and familial partial lipodystrophy. Cases with lamin A/C mutations presenting with lipodystrophy in combination with cardiac and/or skeletal muscle abnormalities are described.

Adult↗
PubMed2002

The influence of long emersion on biota, ammonium fluxes and nitrification in intertidal sediments of Marennes-Oléron Bay, France.

A comparative study between waterlogged and reflooded intertidal sediments was undertaken in March and June 1999 through statistical analysis of selected sediment parameters (biota, salinity, O2, Eh), pool sizes and benthic fluxes of nutrients (NH4+, NO2-, NO3-) and nitrification rates. In March samples, absence of polychaetes and oligochaetes from upper sediment horizons were due to erosional events sweeping away surface sediments. Presence of richer annelid assemblages in June samples indicated more stable hydrodynamic conditions that favoured the development of benthic microalgae biofilms. Dewatering of sediments during a 3-day emersion period promoted a salinity rise on top layers, migration of pore water ions towards the sediment surface, and created sediment fissures that accelerated water exchange on reflooding. Reflooded and waterlogged sediment systems were comparable with respect to the release of NH4+ to overlying water but were different with respect to nitrification rates. Sediment-water NH4+ fluxes were higher (P = 0.011) in March (3.3 mmol m(-2) day(-1) compared to June (1.4 mmol m(-2) day(-1) due to higher macrofauna biomasses and lower benthic microalgae concentrations in March samples. Potential nitrification rates (range from 19 to 60 mmol NO3- (-2) day(-1)) were not statistically different between March and June. A thinner oxic layer in reflooded compared with waterlogged systems reflects a decrease of O2 diffusion into sediment at high salinities which resulted in the fall of the actual nitrification rates (P < 0.05). Our data suggest that long term dessication of intertidal sediments may depress the nitrification process at the ecosystem level.

Analysis of Variance↗
PubMed2002

[Prevention of thromboembolic risk in spinal cord injury: results of a questionnaire concerning short- and long-term treatment].

INTRODUCTION: The use of medications to prevent thromboembolic risk is recommended in spinal cord injury patients during the early phase, but there is no consensus on treatment duration and modalities. Differences in practice include choice of medication (heparin, low molecular weight heparin, inhibitors of platelet aggregation), treatment duration (three to six months or more), and criteria for discontinuation of treatment. GOALS: To determine usual practice modalities for prophylaxis of deep vein thrombosis in spinal cord injury patients, and to identify determinant criteria. METHODS: Postal survey of physiatrists taking care of spinal cord injury patients. The questionnaire asks the physician about his usual practice modalities (choice of treatments, paraclinical tests, use of compressive stockings, during and after the first six months and criteria for discontinuation of treatments). RESULTS: Forty-two questionnaires were suitable for analysis. Results show that usual practice modalities combine venous doppler testing only in the setting of suggestive clinical signs, treatment with low molecular weight heparin during three to six months, and combination with compressive stockings. DISCUSSION: Despite the absence of consensus on this question, our results are consistent with data from the literature, which identify acute spinal cord lesions as a factor of high risk for deep vein thrombosis. The risk decreases during the chronic phase. Adjuvant techniques include mobilisation, elastic compression, and standing. A study of long-term treatment modalities after deep vein thrombosis would be needed.

Bandages↗
PubMed2002

Genetic testing and genetic counselling in hypertrophic cardiomyopathy: the French experience.

AIMS: A major breakthrough in the molecular genetics of hypertrophic cardiomyopathy (HCM) has made genetic testing now available in clinical practice, raising new questions about its implications, potential benefits, and the organisation of the procedure. The aim of this work was (1) to discuss the different questions related to genetic testing in HCM, and propose guidelines for the different situations, (2) to report our preliminary experience with a specific procedure. METHODS AND RESULTS: The main questions asked by patients and relatives concern presymptomatic diagnosis and prenatal counselling/diagnosis, while clinicians sometimes discuss diagnostic and prognostic testing. To take into account the complex medical and psychological implications of this new approach, we developed a specific, multidisciplinary, and multiple step procedure, including a cardiologist, a geneticist, and a psychologist. Seventy subjects were examined, including (1) 29 adults for presymptomatic diagnosis (of whom 10 left the procedure after the first visit and 19 continued, among whom six had a mutation and two experienced negative psychological impact, observed during follow up), (2) nine couples of parents for presymptomatic diagnosis in their children (the procedure was stopped after the first visit in eight and continued in one), (3) 22 couples for prenatal counselling (no prenatal genetic testing was asked for after the first visit), and (4) 10 subjects for diagnostic testing. We decided to perform no prognostic testing. CONCLUSION: Our preliminary experience confirms the complexity of the situation and suggests the necessity for a specific procedure to ensure good practice in genetic testing of HCM.

Adolescent↗
PubMed2001

Cloning and expression of a fungal L-arabinitol 4-dehydrogenase gene.

L-Arabinitol 4-dehydrogenase (EC ) was purified from the filamentous fungus Trichoderma reesei (Hypocrea jecorina). It is an enzyme in the L-arabinose catabolic pathway of fungi catalyzing the reaction from L-arabinitol to L-xylulose. The amino acid sequence of peptide fragments was determined and used to identify the corresponding gene. We named the gene lad1. It is not constitutively expressed. In a Northern analysis we found it only after growth on L-arabinose. The gene was cloned and overexpressed in Saccharomyces cerevisiae, and the enzyme activity was confirmed in a cell extract. The enzyme consists of 377 amino acids and has a calculated molecular mass of 39,822 Da. It belongs to the family of zinc-binding dehydrogenases and has some amino acid sequence similarity to sorbitol dehydrogenases. It shows activity toward L-arabinitol, adonitol (ribitol), and xylitol with K(m) values of about 40 mM toward L-arabinitol and adonitol and about 180 mM toward xylitol. No activity was observed with D-sorbitol, D-arabinitol, and D-mannitol. NAD is the required cofactor with a K(m) of 180 microM. No activity was observed with NADP.

Amino Acid Sequence↗
PubMed2001

Iron porphyrins as models of cytochrome c oxidase.

A series of iron porphyrins has been synthesized as models of cytochrome c oxidase; their activity as 4e catalysts in the reduction of dioxygen has been studied at pH 7. These compounds have been obtained by grafting very different residues onto the same iron complex, namely tripodal tetraamines, pickets, and straps, in order to change the environment of the metal center. In the case of porphyrins bearing a tripodal cap, the secondary amines have been alkylated with different substituents so as to modify the electronic environment of the distal pocket. Surprisingly, when the iron porphyrin is functionalized with four identical acrylamido pickets, the resulting complex exhibits biomimetic activity in that it catalyzes oxygen reduction with almost no production of hydrogen peroxide. The crystal structure of the redox-inactive zinc(II) analogue is reported; this shows how the metal influences the spatial arrangement of the four pickets through axial coordination and hydrogen bonding. Even a bis-strapped iron porphyrin, for which no dimerization or self-aggregation can occur at the electrode surface, acts as a 4e catalyst for O2 reduction. It is thus demonstrated that at pH close to physiological values, the iron porphyrin is an intrinsically efficient catalyst for the reduction of oxygen to water.

Catalysis↗
PubMed2001

Superelastic scattering of electrons from highly charged ions with inner shell vacancies.

We report the measurement of electrons scattered superelastically from highly charged ions having an initial K-shell vacancy. In this process, the scattered electron gains approximately 725 eV of energy from the deexcitation of an excited He-like F7+(1s2s 3S) metastable ion to its ground state. Theoretical calculations based on an R-matrix approach agree well in position, shape, and magnitude with the experimental data.

Journal Article↗