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Biomedical subjects

M Legendre

Publications and source records attributed to M Legendre.

At least 19 recordsLinked to original sources

Air bubbles under vertical vibrations.

This paper reports on an experimental study of the splitting instability of an air bubble a few centimetres in diameter placed in a sealed cylindrical cell filled with liquid and submitted to vertical oscillations. The response of the bubble to the oscillations is observed with a high-speed video camera. It is found that the bubble dynamics is closely associated with the acceleration of the cell Gamma. For small acceleration values, the bubble undergoes minor shape deformations. With increasing acceleration values, these deformations are amplified and for sufficiently large Gamma the bubble becomes toroidal. The bubble may then become unstable and split into smaller parts. The onset of bubble division is studied and its dependency on physical parameters such as the fluid viscosity, the fluid surface tension and the initial size of the bubble is presented. It is found that the criterion for the bubble splitting process is associated with a threshold based on the acceleration of the oscillations. Above this threshold, the number of bubbles present in the cell is observed to grow until a final steady state is reached. Data analysis reveals that the final bubble size may be characterized in terms of Bond number.

Journal Article↗

Intrafamilial segregation analysis of the p.E148Q MEFV allele in familial Mediterranean fever.

BACKGROUND: Familial Mediterranean fever (FMF) is the most frequent of the recurrent inherited fevers. This autosomal recessive disorder is characterised by periodic episodes of fever and serositis that commonly affect the people of Arab, Armenian, Sephardic Jewish and Turkish origin. Most of the described MEFV gene anomalies responsible for the disease are missense mutations. In the absence of any functional test, epidemiological studies or pedigree analyses are the only means of proving the deleterious character of these sequence variations. Evidence was provided by our recent study using a population-based approach, that the p.E148Q allele is probably a benign polymorphism and not a disease-causing mutation. Its implication in FMF remains, however, controversial. OBJECTIVE: To evaluate the segregation of the p.E148Q MEFV allele with FMF disease by using pedigree analysis. PARTICIPANTS: 21 patients and 48 unaffected relatives belonging to 18 independent families with FMF. RESULTS: Segregation analysis of the p.E148Q allele was compatible with a Mendelian autosomal recessive transmission of the disease phenotype in only three families. In 15 of 18 families, segregation was partly or completely defective. The p.E148Q allele was not transmitted to 14 of 19 (74%) affected children. CONCLUSIONS: No evidence of preferential transmission of p.E148Q from heterozygous parents to their affected offspring was observed. MEFV is not associated with the clinical manifestations of several patients carrying this variant. Considering p.E148Q to be a benign polymorphism should reduce the possibility of false-positive diagnoses, while highlighting genetic heterogeneity in FMF.

Adolescent↗

A new large CFTR rearrangement illustrates the importance of searching for complex alleles.

The p.Val754Met variant, described in 1996 in a CF patient, has been considered a CF mutation. However, biochemical aspects, results of functional studies and, finally, the identification of a complex deletion removing exons 3 to 10 and 14b to 16 in cis of p.Val754Met in a CF patient, argue against a strong deleterious effect. An inventory through the French CF network of patients carrying p.Val754Met led to the registration of seven patients (CF: n=4; idiopathic chronic pancreatitis: n=3) and six healthy individuals, all heterozygous for the variation. Extensive CFTR gene analysis was carried out, including the search for large rearrangements and other possible mutations. The complex deletion, whose breakpoints are described here, was found only in the four CF patients, in association with the same haplotype. This data, added to the fact that the p.[Phe508del]+[Val754Met] genotype was found in a healthy individual, bring further arguments against the association of p.Val754Met with CF. We thus suggest looking for a possible complex allele whenever p.Val754Met is detected and considering it neutral regarding genetic counseling when found in isolation.

Adolescent↗

MEFV analysis is of particularly weak diagnostic value for recurrent fevers in Western European Caucasian patients.

OBJECTIVE: Familial Mediterranean fever (FMF) is an autosomal-recessive disorder characterized by recurrent attacks of fever, with abdominal, thoracic, or articular pain. FMF is particularly common in Mediterranean populations, while other populations are rarely affected. MEFV gene analysis provides the only objective diagnostic criterion for FMF. However, the spectrum of MEFV mutations, which was first established in classically affected populations, remains insufficiently studied in other populations. The purpose of this study was to assess involvement of MEFV in the phenotype of western European Caucasian patients with a clinical diagnosis of FMF. METHODS: Mutation analysis was performed in 208 Caucasian patients from western Europe, by screening for the most common MEFV mutations in exons 2, 3, 5, and 10, and by sequencing the promoter region and the whole MEFV coding sequence in 21 of these patients. RESULTS: None of the patients carried 2 mutated alleles. Only 2 patients carried 1 mutated allele. CONCLUSION: FMF-like syndromes in western European Caucasian populations cannot be explained by MEFV mutations. These results should be helpful in avoiding laborious and costly MEFV molecular analyses that, at the population level, seem to be of poor diagnostic value in the case of western European Caucasian patients, and rather should prompt a search for other causes in those patients.

Cytoskeletal Proteins↗

Clinical efficacy and safety of fluticasone propionate 250 microg twice daily administered via a HFA 134a pressurized metered dose inhaler to patients with mild to moderate asthma. French study group.

This study compared the efficacy and safety of the fluticasone propionate 125 microg pressurized metered dose inhaler (pMDI) propelled by either hydrofluoroalkane (HFA) 134a or chlorofluorocarbon (CFC) propellants, in adult patients with asthma. HFA 134a is a non-ozone depleting propellant used as a replacement for the CFC propellants 11 and 12 which are being phased out in accordance with the Montreal Protocol. Three hundred and eighty patients with mild to moderate asthma and 'room for improvement' in their treatment were randomized to receive fluticasone propionate 250 microg twice daily via pMDIs propelled by either CFC propellants 11 and 12 (n = 195) or HFA 134a (n = 185). Fluticasone propionate significantly improved lung function over the 4-week treatment period in both treatment groups. The improvement in mean morning peak expiratory flow (PEF) after 7 days of treatment was approximately 12 l min(-1) in both groups, rising to approximately 22 l min(-1) at the end of the 4-week treatment period. The adjusted mean difference between the two formulations over weeks 1-4 was -1 l min(-1) (90% confidence interval: -7, 5 l min(-1)), confirming their equivalence. Clinical comparability was also demonstrated with respect to secondary efficacy variables, including daily symptom scores, evening PEF and clinic visit expiratory measurements. There were no clinically relevant differences in adverse events or serum cortisol levels between the two groups. The fluticasone propionate 125 microg HFA 134a pMDI is an effective and well tolerated product and is a suitable replacement for the fluticasone propionate 125 microg CFC pMDI at a microgram equivalent dose.

Administration, Inhalation↗

[Anti-angina effect of amiodarone versus delayed-action propranolol. A double-blind randomized study].

Long-acting Propranolol (160 mg/day) and Amiodarone (200 mg/day after impregnation) were compared in chronic stable angina pectoris. Forty-three patients with stable angina of effort were included in a randomised double blind trial (19 in the amiodarone and 24 in the propranolol group). The duration of the study was 8 weeks; the placebo phase (2 weeks) was followed by 6 weeks of active treatment. An exercise stress test was performed before and after the treatment period. The number of episodes of angina and the consumption of glyceryl trinitrate decreased significantly (p less than 0.001) in the same proportion with both drugs with respect to the placebo period. The time to the appearance of criteria of positivity of the exercise stress test increased from 6.82 +/- 0.50 mn to 8.35 +/- 0.50 mn with amiodarone, and from 7.15 +/- 0.47 mn to 9.50 +/- 0.52 with the propranolol preparation. This improvement was very significant compared with the placebo phase (p less than 0.001) but the difference between the two drugs was not statistically significant (p = 0.39). The other parameters which were studied (time to onset of angina, total duration of exercise, maximum heart rate, double product, maximum ST depression) changed in a parallel fashion significantly versus placebo. There were no differences between the two treatment groups with the exception of the resting heart rate which decreased more in patients on propranolol (80.94 +/- 3.92 to 62.47 +/- 1.97) than in patients on amiodarone (84.87 +/- 2.63 to 73.41 +/- 2.01; p less than 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Therapeutic problems posed by hemiballism of metastatic origin].

A 40 year old woman undergoing treatment for cancer of the breast presented with metastatic hemiballism. Diagnosis was supported by the presence of bone and liver metastases and by CT-scan showing an enhanced rapidly growing lesion in the subthalamic region contralateral to hemiballism. Treatment by corticotherapy and neuroleptics was ineffective. Radiotherapy was unsuccessful. Metastatic hemiballism is a rare disease with no effective treatment.

Adult↗

[Respiratory manifestations in hereditary angioneurotic edema].

Hereditary angioneurotic oedema is an autosomal dominant state associated with a quantitative, and sometimes purely functional, deficiency of C1 esterase inhibitor (C1 INH). The clinical manifestations may begin during adulthood or childhood; they are periodical and of varying severity. Beside oedema of the skin and digestive disorders, respiratory disorders are bound to attract attention. They consist of laryngeal oedema, which may end in lethal asphyxia if tracheotomy is not performed, or, exceptionally, of pulmonary oedema requiring assisted ventilation, as in the case reported here. The diagnosis, suspected in the presence of a decrease in CH50 and C4, is confirmed by a quantitative assay of C1 INH, which is low, and/or by the Fong and Good's functional tests. The physiopathological mechanisms are complex. They involve complement activation through the classical route, and activation of the coagulation system contact phase. Patients with severe attacks now benefit from treatment with preparations of C1 INH in high concentrations. The best treatment, however, is prophylactic, using testosterone derivatives, danazol and stanozolol, which can be prescribed for long periods taking into account their usually moderate side-effects.

Acute Disease↗

[Metabolism of fenofibrate and fenofibric acid in vivo and in cultures of liver epithelial cells (author's transl)].

In vitro and in vivo studies using capillary column gas chromatography alone or coupled with mass spectrometry resulted in the identification of several metabolites of fenofibrate (LF 178). Fenofibric acid (LF 153) was omnipresent, being found in rats after acute, subacute and chronic administration, in human urine during chronic treatment, and in cultures of rat and human liver cells. Other metabolites were LF 433 (LF 153 benzhydrol), which increases in rats with the duration of treatment while LF 153 decreases, and LF - phenol" found in human urine. In hepatocyte cultures, fenofibric acid was predominant, but fenofibrate itself and LF 321 (LF 178 benzhydrol) were also present in addition to the above-mentioned metabolites. LF 321, however, was only found in human liver cell cultures.

Animals↗

Cryopreservation of rainbow trout sperm by deep-freezing.

Cryopreservation trials on rainbow trout (Salmo gairdneri) sperm were carried out using two basic extenders: Mounib's medium (M) and Ménézo's medium (Me) to which were added bovine serum albumin (BSA) and tellurite egg yolk (Institut Pasteur). After 10 p. 100 of DMSO was added to these different deep-freeze diluents (DD), they were mixed with the sperm and then deep-frozen into 100 microliter pellets on dry ice. The pellets were stored in liquid nitrogen for periods lasting from 3 days to 6 months. The intensity of sperm motility and fertilizing ability were measured before and after cryopreservation. After the sperm was diluted in Ménézo's medium, slight spermatozoon motility was noticed, which probably caused their early exhaustion and would explain the lower fertilizing ability observed after thawing. Mounib's medium gave better results, especially after 10 p. 100 of egg yolk was added. The optimal deep-freeze conditions were: 1/3 dilution, no equilibration after dilution but immediate deep-freezing at a rate of 10 to 40 degrees C/min. Thawing had to be carried out rapidly in 10 sec. However, the spermatozoa were altered during the freezing-thawing process, and during insemination more frozen spermatozoa had to be used to equal the fertilization rate obtained with non-frozen sperm. However, the fertile spermatozoa gave normal embryogenesis and no abnormal development was seen up to the vesicle resorption stage. At the end of spermiation, sperm fitness for deep-freezing decreased, perhaps due to sperm senescence. Pooling the sperm of several males partially compensated for the loss of fertilizing ability seen at the end of the reproductive period.

Animals↗

Comparative efficacy of short-acting and long-acting quinidine for maintenance of sinus rhythm after electrical conversion of atrial fibrillation.

Forty patients with chronic atrial fibrillation, apparently unrelated to any overt heart disease, were randomly allocated to two groups after restoration of sinus rhythm by direct current shock. The patients in group A were given 4 daily doses of quinidine polygalacturonate, while those in group B were given 2 daily doses of a long-acting quinidine preparation, quinidine arabogalactan sulphate. The percentage of early relapses (within the first month following DC shock) was not significantly different in the two groups: 44-4% in group A and 35% in group B (P greater than 0-50). On the other hand, there were fewer late relapses with long-acting quinidine. After 18 months of treatment, 27-8% of patient in group A remained in sinus rhythm, compared with 61% in group B (P less than 0-05). The average amount of quinidine actually ingested by the patients in group A was smaller than that in group B. However, this could not entirely account for the difference observed in the incidence of relapse since with short-acting quinidine the proportion of patients remaining in sinu rhythm was similar whether the dose was decreased or not. The incidence of gastrointestinal side-effects was the same in the two groups and there were no seriou complications that could be attributed to treatment. It is concluded that long-acting quinidine preparations are more effective than conventional quinidine in preventing late relapses of atrial fibrillation.

Aged↗

Use of high-resolution open tubular glass capillary columns to separate acidic metabolites in urine.

We used high-resolution glass capillary columns to study the trimethylsilyl derivatives of some acidic metabolites found in pooled urine specimens form control and postpartum subjects. About 30 compounds were identified by gas chromatography-mass spectrometry-computer techniques. In general, open tubular capillary columns effect better resolution of trimethylsilyl derivatives of organic acids than do conventional packed columns. GESE-30 proved to be a good general-purpose stationary phase, whereas OV-17 offered certain advantages in resolving aromatic acid components.

Adult↗