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Biomedical subjects

H Levesque

Publications and source records attributed to H Levesque.

At least 55 records · Page 3Linked to original sources

Increased hyaluronan and hyaluronidase production and hyaluronan degradation in injured aorta of insulin-resistant rats.

Diabetic patients have a greater incidence of restenosis, which has been shown to be related to exaggerated intimal hyperplasia. Hyaluronan (HA) has been shown to be closely involved in arterial smooth muscle cell proliferation and migration, which provoke intimal hyperplasia after balloon catheter injury. Our aim was to determine the effect of fructose feeding, which produces certain characteristics of non-insulin-dependent diabetes (ie, insulin resistance, hyperinsulinemia, and hypertriglyceridemia), on production of HA and hyaluronidase and degradation of HA in rat aorta. Treated rats received fructose (25% in tap water) 12 weeks before balloon catheter injury and 14 days afterward. Fructose-fed rats had hyperinsulinemia and hypertriglyceridemia. Injury increased intima-media wet weight (7.5%) and DNA content (20%) in control rats. This increase was significantly greater in fructose-fed rats (22% for wet weight and 34% for DNA content) and was associated with greater HA and hyaluronidase production (123% and 41%, respectively) than in control rats (49% and 7%, respectively). Determination of HA molecular mass showed that balloon catheter injury increased the number of HA fragments in the aorta of control rats. Normal aorta of fructose-fed rats contained more HA fragments than that of control rats. Injury to the aorta of fructose-fed rats increased HA fragments and induced the appearance of a very-high-molecular-mass (>2000 kDa) HA. In conclusion, fructose treatment, which induced hyperinsulinemia and hypertriglyceridemia, increased HA and hyaluronidase production and HA degradation in injured aorta. This finding suggests that HA, which has been shown to play a crucial role in proliferation and migration of arterial smooth muscle cells, may be involved in the promotional effect of long-term fructose feeding on arterial wall reaction to injury.

Animals↗

Hypertrophic osteoarthropathy can indicate recurrence of Whipple's disease.

We report the case of a patient with Whipple's disease (WD) who developed hypertrophic osteoarthropathy (HOA) characterized by digital clubbing, periostosis of the tubular bones, and polysynovitis. The HOA disclosed the recurrence of the patient's WD, since polymerase chain reaction (PCR) analysis clearly demonstrated the presence of Tropheryma whippelii in the synovial fluid from the patient's left knee. Initiation of appropriate antibiotic therapy resulted in complete healing of all clinical rheumatologic manifestations within 2 months and in disappearance of radiographic bone changes at 7-month followup. We suggest that HOA be included within the spectrum of rheumatologic manifestations of WD, and that an evaluation for WD should be considered in patients, especially middle-aged men, presenting with HOA even without gastrointestinal symptoms. PCR analysis may be useful in accurate diagnosis and management of early WD with unusual clinical manifestations, and may contribute to decreased morbidity and mortality.

Anti-Bacterial Agents↗

Influence of age on characteristics of polymyositis and dermatomyositis in adults.

In a retrospective study of 79 consecutive patients, we evaluated characteristics of polymyositis (PM) and dermatomyositis (DM) and compared clinical presentation, biochemical findings, histologic changes, evolution, complications, and mortality rate of elderly patients (aged > or = 65 yr) and younger patients (aged < or = 64 yr) at the onset of PM/DM. We found a high prevalence of PM/DM in elderly patients: 23 patients (29%) were aged 65 years or over. We also found that esophageal involvement (34.8% versus 16.1%, respectively) and bacterial pneumonia related to both ventilatory insufficiency and esophageal impairment (21.7% versus 5.4%, respectively) were more common in elderly patients compared with younger patients, resulting in increased morbidity and mortality rates. Moreover, malignancy frequency was higher in elderly patients compared with younger patients (47.8% versus 9.1%, respectively, p = 0.0001), particularly patients with DM (10/11). Fifty percent of malignancies were colon malignancies in elderly patients. Erythrocyte sedimentation rate, C-reactive protein, fibrinogen, and ferritin levels were also higher in the elderly patient group compared with the younger group, and the presence of serum hypoprotidemia, hypoalbuminemia, and anemia was more frequent. Finally, PM/DM complete remission was less frequent (13.6% versus 41.1%) and the mortality rate (47.8% versus 7.3%) was higher in elderly patients than in younger patients. The main causes of death in elderly patients were bacterial pneumonia, due to ventilatory insufficiency and esophageal impairment, and malignancies. Our findings therefore indicate that PM/DM-related esophageal and lung involvement should be systematically searched for in elderly patients. Esophageal manometry and pulmonary function tests should become an integral part of initial evaluation in elderly patients for early detection of impairment. Moreover, as we observed a marked overrepresentation of colon cancer in elderly patients with DM, we suggest that the search for malignancies in elderly patients with DM should include lower gastrointestinal tract investigations.

Activities of Daily Living↗

Intravenous immunoglobulins as treatment of life threatening esophageal involvement in polymyositis and dermatomyositis.

Esophageal involvement is considered a major cause of morbidity and an indicator of poor prognosis in polymyositis (PM) and dermatomyositis (DM). We describe 3 patients with steroid resistant PM/DM with life threatening esophageal involvement, resulting in impossible oral feeding and enteral nutrition with a gastric tube. All patients had both dramatic and rapid improvement of all clinical manifestations after initiation of intravenous immunoglobulin (IVIG) therapy. Swallowing disorders completely disappeared after the second infusion of IVIG, which permitted normal oral feeding and ablation of the gastric tube. Our findings suggest IVIG should be considered the treatment of choice in such cases.

Adult↗

Manometry of the upper intestinal tract in patients with systemic sclerosis: a prospective study.

OBJECTIVE: To assess both the prevalence and the characteristics of motor disorders of the small bowel in patients with systemic sclerosis (SSc) and to investigate for an association between clinical manifestations in the upper intestinal tract, capillaroscopic features, esophageal motor impairment, and manometric evidence of motor disturbances. METHODS: Fasting and postprandial motor activity of the upper intestinal tract was studied in 17 consecutive patients with SSc (6 with and 11 without clinical manifestations of small bowel involvement) and 17 age- and sex-matched healthy control subjects. RESULTS: The prevalence of manometric evidence of intestinal involvement was as high as 88% in the SSc patients; normal motor activity was present in only 2 patients. The median values for duodenal and jejunal interdigestive phase III migrating motor complex duration, amplitude, and velocity and the postprandial motility index were therefore lower in SSc patients compared with controls. Our manometric findings indicated that there are both neuropathic and myopathic stages of upper intestinal tract dysfunction in SSc. Furthermore, no association could be found between the severity of the intestinal manometric abnormalities and clinical presentation, SSc subsets, disease score, capillaroscopic findings, or esophageal manometric impairment. CONCLUSION: We suggest that manometry of the upper intestinal tract may be useful in SSc patients with clinical manifestations in the small bowel (i.e., malabsorption syndrome or pseudoobstruction) in that it can be used to accurately evaluate both the nature and the severity of motor disturbances. Furthermore, this procedure can be used to assist in the selection of patients who may require octreotide therapy.

Adult↗

[Role of hyaluronic acid in the arterial response to angioplasty].

Angioplasty has become enormously popular since its introduction in 1979 for the treatment of arterial stenosis at coronary or other sites. The success rate is currently around 95%. Unfortunately, restenosis occurs in 30 to 40% of cases within six months of the procedure. Restenosis is the result of a number of events that are triggered by the angioplasty. These events involve both blood components (platelets, leukocytes, and plasma constituents) and arterial wall components (smooth muscle cells [SMCs], endothelial cells, and the extracellular matrix). Hyaluronate is a high-molecular-weight glycosaminoglycane found in the extracellular matrix of arterial SMCs and endothelial cells. Hyaluronate and its receptors (CD44 and RHAMM or receptor for HA-mediated motility) contribute actively to leukocyte adhesion and infiltration at experimental angioplasty sites. Studies of cell cultures have shown that leukocyte adhesion and migration are inhibited by substances (antibodies, peptides, high levels of hyaluronate) that prevent hyaluronate from binding to CD44 and RHAMM. Hyaluronate expression by arterial SMCs is modulated by the angioplasty-produced arterial lesion. The SMCs that migrate and divide actively at the arterial lesion site are those that express hyaluronate, CD44, and RHAMM. Hyaluronate both stimulates SMC migration via an effect on RHAMM and enhances SMC division via an effect on CD44. In animal studies, administration of high levels of hyaluronate to saturate hyaluronate receptors on leukocytes and SMCs was followed by inhibition of leukocyte infiltration into the damaged arterial wall and by a significant reduction in the arterial neointima. Hyaluronate, a compound with an excellent safety profile, may offer hope for the prevention of restenosis after angioplasty.

Angioplasty↗

The nucleotide sequence of Saccharomyces cerevisiae chromosome XIV and its evolutionary implications.

In 1992 we started assembling an ordered library of cosmid clones from chromosome XIV of the yeast Saccharomyces cerevisiae. At that time, only 49 genes were known to be located on this chromosome and we estimated that 80% to 90% of its genes were yet to be discovered. In 1993, a team of 20 European laboratories began the systematic sequence analysis of chromosome XIV. The completed and intensively checked final sequence of 784,328 base pairs was released in April, 1996. Substantial parts had been published before or had previously been made available on request. The sequence contained 419 known or presumptive protein-coding genes, including two pseudogenes and three retrotransposons, 14 tRNA genes, and three small nuclear RNA genes. For 116 (30%) protein-coding sequences, one or more structural homologues were identified elsewhere in the yeast genome. Half of them belong to duplicated groups of 6-14 loosely linked genes, in most cases with conserved gene order and orientation (relaxed interchromosomal synteny). We have considered the possible evolutionary origins of this unexpected feature of yeast genome organization.

Base Sequence↗

Benefit of a 2-month treatment with a micronized, purified flavonoidic fraction on venous ulcer healing. A randomized, double-blind, controlled versus placebo trial.

OBJECTIVE: To assess the efficacy of a micronized purified flavonoid fraction (Daflon 500 mg = Dios) in venous leg ulcer healing, in addition to compression therapy and standardized local care. DESIGN: Double-blind, multicentre, randomized, parallel groups, controlled versus placebo trial; stratification according to ulcer size. SUBJECTS: 107 patients, with venous ulcer of the leg for at least 3 months, and accepting bandaging therapy. RESULTS: 105 patients (Dios = 53, placebo = 52) were available for an intention to treat (ITT) analysis. Age (mean +/- SD, 71+/-11 years), gender (M = 33, F = 74) and ulcer size were evenly distributed among both groups. 99 patients completed the protocol (Dios = 51, placebo = 48). Among the 91 patients with ulcer size < or = 100 cm (Dios = 44, placebo = 47), a significantly higher number of patients had complete ulcer healing at 2 months in the Dios group (n = 14) in comparison to the placebo group (n = 6) after ITT analysis (32 vs. 13%, p = 0.028) and after per protocol analysis (32 vs. 14%, p = 0.048), and a shorter time duration of healing (p = 0.037). Among the 14 patients with ulcer size > 10 cm (Dios = 9, placebo = 5), no ulcer healed. CONCLUSION: This study showed that a 2-month course of purified micronized flavonoid fraction (2 tablets/day), in addition to conventional treatment, is of benefit in patients by accelerating complete healing of venous leg ulcers which are < or = 10 cm in diameter.

Adolescent↗