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Biomedical subjects

E Gagné

Publications and source records attributed to E Gagné.

14 recordsLinked to original sources
PubMed2000

Redefining Rowell's syndrome.

Rowell's syndrome is believed to be a distinct and rare clinical entity originally described as lupus erythematosus associated with erythema multiforme-like lesions with immunological findings of speckled antinuclear antibodies, anti-La antibodies and a positive test for rheumatoid factor. We report two additional patients with Rowell's syndrome and review all the diagnostic criteria found in the literature. In view of the inconsistent findings of some of the diagnostic features, we propose that major and minor criteria be used to diagnose Rowell's syndrome.

Erythema Multiforme↗
PubMed2000

Calciphylaxis: seven new cases.

BACKGROUND: Calciphylaxis is a rare condition occurring most frequently in patients with end-stage renal disease (ESRD). It is characterized by vascular calcifications with a large variety of skin lesions. Even though this entity was first reported almost 50 years ago, the pathogenesis is still not well understood. OBJECTIVE: Having retrieved seven new cases from a single tertiary care hospital, the disease occurs probably more frequently than reported until now. The potential mechanism of action in this disease is discussed, particularly the hypercoagulability state. We also review potential treatments described in the literature. METHODS: Seven patients with calciphylaxis that occurred at the Hôtel-Dieu hospital between 1992 and 1998 were identified and their case histories reviewed and analyzed. CONCLUSION: Although hyperparathyroidism and imbalance of calcium-phosphorus homeostasis are paramount for calciphylaxis to occur, other mechanisms must be involved because the disease manifests itself in only a minority of ESRD patients. As the majority were under anticoagulation therapy and as we found abnormalities of the coagulation pathway in one patient, we suggest emphasizing these phenomena in the future. Along with evaluation of putative risk factors (abnormalities of the calcium:phosphate axis, diabetes), a detailed evaluation of the coagulation system should be done in every patient with calciphylaxis until more data are available.

Adult↗
PubMed1999

Lipoprotein lipase activity is decreased in a large cohort of patients with coronary artery disease and is associated with changes in lipids and lipoproteins.

Lipoprotein lipase (LPL) is crucial in the hydrolysis of triglycerides (TG) in TG-rich lipoproteins in the formation of HDL particles. As both these lipoproteins play an important role in the pathogenesis of atherosclerotic vascular disease, we sought to assess the relationship between post-heparin LPL (PH-LPL) activity and lipids and lipoproteins in a large, well-defined cohort of Dutch males with coronary artery disease (CAD). These subjects were drawn from the REGRESS study, totaled 730 in number and were evaluated against 75 healthy, normolipidemic male controls. Fasting mean PH-LPL activity in the CAD subjects was 108 46 mU/ml, compared to 138 44 mU/ml in controls (P < 0.0001). When these patients were divided into activity quartiles, those in the lowest versus the highest quartile had higher levels of TG (P < 0.001), VLDLc and VLDL-TG (P = 0.001). Conversely, levels of TC, LDL, and HDLc were lower in these patients (P = 0.001, P = 0.02, and P = 0.001, respectively). Also, in this cohort PH-LPL relationships with lipids and lipoproteins were not altered by apoE genotypes. The frequency of common mutations in the LPL gene associated with partial LPL deficiency (N291S and D9N carriers) in the lowest quartile for LPL activity was more than double the frequency in the highest quartile (12.0% vs. 5.0%; P = 0.006). By contrast, the frequency of the S447X LPL variant rose from 11.5% in the lowest to 18.3% (P = 0.006) in the highest quartile. This study, in a large cohort of CAD patients, has shown that PH-LPL activity is decreased (22%; P = 0.001) when compared to controls; that the D9N and N291S, and S447X LPL variants are genetic determinants, respectively, in CAD patients of low and high LPL PH-LPL activities; and that PH-LPL activity is strongly associated with changes in lipids and lipoproteins.

Adult↗
PubMed1998

Micronodular pneumocyte hyperplasia.

Tuberous sclerosis complex (TSC) is an autosomal-dominant disorder characterized by mental retardation, seizures, and central nervous system and visceral hamartomas. Pulmonary involvement manifesting as lymphangioleiomyomatosis (LAM) occurs in 1% of patients (all women) with TSC. Micronodular pneumocyte hyperplasia also has been described as a rare pulmonary manifestation of TSC. We report 14 patients with micronodular pneumocyte hyperplasia (MNPH). The patients ranged in age from 23 to 57 years (mean 37.5). There were 12 women and 2 men. Nine of the patients (one man and eight women) had documented clinical manifestations of TSC: seven with LAM, two without LAM (including one man). Of the five patients who did not have TSC, three had LAM and two did not (including one man). Histologically, all 14 cases demonstrated multiple well-demarcated nodules usually measuring up to 8 mm in size, but most were 1-3 mm. The nodules were produced by a proliferation of enlarged cytologically benign type II pneumocytes, with an associated increase in alveolar macrophages and interstitial reticulin. Immunoperoxidase studies showed the type II pneumocytes within lesions to be reactive with antibodies to cytokeratin (four of four), epithelial membrane antigen (EMA) (five of five), and surfactant apoprotein B (8 of 10). HMB-45 was negative in the MNPH lesions in all nine cases studied. Follow-up was available in 9 of 10 living patients and ranged from 1 to 14 years (mean 6 years). Nine patients are alive; six are clinically stable and three have repeated pneumothoraces related to LAM. Four patients have died. None of the deaths were attributable to MNPH. MNPH appears to be a hamartomatous proliferation occurring most frequently in patients with tuberous sclerosis, is separable from and not a manifestation of LAM, has been observed to occur in men, and, like other hamartomas of tuberous sclerosis, does not appear to possess malignant potential.

Adult↗
PubMed1997

Genetic variant showing a positive interaction with beta-blocking agents with a beneficial influence on lipoprotein lipase activity, HDL cholesterol, and triglyceride levels in coronary artery disease patients. The Ser447-stop substitution in the lipoprotein lipase gene. REGRESS Study Group.

BACKGROUND: Lipoprotein lipase (LPL) is the rate-limiting enzyme in the lipolysis of triglyceride-rich lipoproteins, and the gene coding for LPL is therefore a candidate gene in atherogenesis. We previously demonstrated that two amino acid substitutions in LPL, the Asn291-Ser and the Asp9-Asn, are associated with elevated triglycerides and lower HDL cholesterol and are present with greater frequency in coronary artery disease (CAD) patients than in normolipidemic control subjects. Conversely, a third frequent mutation in this gene, the Ser447-Stop, is reported by some investigators to underlie higher HDL cholesterol levels and would represent a beneficial genetic variant in lipoprotein metabolism. We therefore sought conclusive evidence for these allegations by investigating the effects of the LPL Ser447-Stop mutation on LPL and hepatic lipase (HL) activity, HDL cholesterol, and triglycerides in a large group of CAD patients (n = 820) with normal to mildly elevated total and LDL cholesterol levels. METHODS AND RESULTS: Carriers of the Ser447-Stop allele (heterozygotes and homozygotes) had significantly higher postheparin LPL activity (P = .034), normal postheparin HL activity (P = .453), higher HDL cholesterol levels (P = .013), and lower triglyceride levels (P = .044) than noncarriers. The influence of the Ser447-Stop allele on LPL activity was pronounced in patients using beta-blockers (P = .042) and not significant in those not using them (P = .881), suggesting a gene-environment interaction between the Ser447-Stop mutation and beta-blockers. CONCLUSIONS: We conclude that the LPL Ser447-Stop mutation has a significant positive effect on LPL activity and HDL cholesterol and triglyceride levels and that certain subgroups of CAD patients carrying the Ser447-Stop mutation will have less adverse metabolic effects when placed on beta-blockers. The LPL Ser447-Stop mutation therefore should have a protective effect against the development of atherosclerosis and subsequent CAD.

Adrenergic beta-Antagonists↗
PubMed1996

The Asp9 Asn mutation in the lipoprotein lipase gene is associated with increased progression of coronary atherosclerosis. REGRESS Study Group, Interuniversity Cardiology Institute, Utrecht, The Netherlands. Regression Growth Evaluation Statin Study.

BACKGROUND: Many patients suffering from premature coronary artery disease report a family history for such events. A mutation in a particular gene, which confers susceptibility for atherosclerosis, will be found more frequently in individuals suffering from coronary atherosclerosis than in the general population. We have recently reported the identification of an Asp9 Asn substitution in the lipoprotein lipase (LPL) enzyme. We analyzed the impact of this mutation on the progression of coronary atherosclerosis and the effect of pravastatin in both carriers and noncarriers. METHODS AND RESULTS: All patients were enrolled in the quantitative coronary angiographic clinical trial REGRESS, which studied the impact of pravastatin therapy on coronary atherosclerosis. The Asp9 Asn mutation was identified in 38 of 819 (4.8%) patients. Carriers of the mutation more often had a positive family history of cardiovascular disease and lower HDL cholesterol levels than noncarriers. In the placebo group, carriers showed more progression of coronary atherosclerosis than noncarriers: mean reduction of the minimum obstruction diameter of -0.25 mm versus -0.12 mm (P = .029) and increase of percentage diameter stenosis of 6.4% versus 1.4% (P = .004). Moreover, the adjusted relative risk for a clinical event for carriers was calculated at 2.16 (95% CI, 1.09 to 4.29; P = .027). Although the lipid-lowering effect of pravastatin was attenuated in carriers, it appeared that these patients showed a response similar to noncarriers in terms of less progression of atherosclerosis and event-free survival. CONCLUSIONS: This study shows that heterozygosity for a mutation in the LPL gene, which causes only subtle changes in fasting plasma lipids, may promote the progression of coronary atherosclerosis and diminish clinical event-free survival.

Amino Acid Sequence↗
PubMed1996

Complete paternal isodisomy for chromosome 8 unmasked by lipoprotein lipase deficiency.

Uniparental disomy (UPD)-the inheritance of two homologous chromosomes from a single parent-may be unmasked in humans by the unexpected appearance of developmental abnormalities, genetic disorders resulting from genomic imprinting, or recessive traits. Here we report a female patient with familial chylomicronemia resulting from complete lipoprotein-lipase (LPL) deficiency due to homozygosity for a frameshift mutation in exon 2 of the LPL gene. She was the normal term product of an unremarkable pregnancy and had shown normal development until her current age of 5.5 years. The father (age 33 years) and the mother (age 24 years) were unrelated and healthy, with no family history of stillbirths or malformations. The father was a heterozygous carrier of the mutation, whereas no mutation in the LPL gene was detected in the mother. Southern blotting did not reveal any LPL gene rearrangement in the proband or her parents. The proband was homozygous for 17 informative markers spanning both arms of chromosome 8 and specifically for the haplotype containing the paternally derived LPL gene. This shows that homozygosity for the defective mutation in the LPL gene resulted from a complete paternal isodisomy for chromosome 8. This is the first report of UPD for chromosome 8 unmasked by LPL deficiency and suggests that normal development can occur with two paternally derived copies of human chromosome 8.

Adult↗
PubMed1996

Lack of association of the apolipoprotein A-I-C-III-A-IV gene XmnI and SstI polymorphisms and of the lipoprotein lipase gene mutations in familial combined hyperlipoproteinemia in French Canadian subjects.

Familial combined hyperlipoproteinemia (FCH) is a common familial lipoprotein disorder characterized by elevated plasma cholesterol and triglyceride levels with segregation in first-degree relatives. Most affected subjects with FCH have elevated plasma levels of apolipoprotein (apo) B. The disorder results from oversecretion of hepatic apoB-containing lipoprotein particles. The genetic defect(s) are unknown. Previous work has suggested that genetic polymorphisms of the apoA-I gene and functional abnormalities of the lipoprotein lipase (LPL) gene are associated with FCH. We investigated the XmnI and SstI restriction fragment length polymorphisms (RFLP) of the apoA-I gene in FCH subjects of French Canadian descent. We also investigated three common functional mutations of the lipoprotein lipase (LPL) gene (LPLGly188Glu, LPLPro207Leu, and LPLAsp250Asn) in French Canadians that account for approximately 97% of cases of complete LPL deficiency in the province of Québec, Canada. We identified and characterized 54 FCH probands in lipid clinics and examined at least one first-degree relative. There were 37 men and 17 women (mean age 48 +/- 9 and 58 +/- 8 years, respectively). None of the probands had diabetes mellitus; mean plasma glucose was 5.5 mmol/L. High blood pressure was diagnosed in 32% of men and 29% of women. The body mass index (weight (kg)/height(m2)) was elevated in probands (27 +/- 4 for men and 26 +/- 4 for women). Mean plasma levels of cholesterol (C) was 7.6 +/- 1.5 mmol/L, triglycerides 3.5 +/- 1.6 mmol/L, LDL-C 4.9 +/- 1.2 mmol/L, HDL-C 1.0 +/- 0.3 mmol/L, and apoB 1.83 +/- 0.67 g/L in the probands. Allele frequency of the rare alleles of the XmnI and SstI RFLP was not significantly different from a healthy reference group. In several families studied, the XmnI and SstI RFLP did not unequivocally segregate with the FCH phenotype. There was no significant effect of the presence or absence of the XmnI or SstI RFLP's on plasma lipids, lipoprotein cholesterol or apoB levels. Only one FCH proband was found to have a mutation of the LPL gene (Gly188Glu), and this did not segregate with the FCH phenotype in the family. We conclude that in our highly selected group of FCH subjects of French Canadian descent, the XmnI and SstI RFLPs of the apoA-I gene and common functional mutations of the LPL gene resulting in complete LPL deficiency are not associated with FCH.

Adult↗
PubMed1995

A lipoprotein lipase mutation (Asn291Ser) is associated with reduced HDL cholesterol levels in premature atherosclerosis.

A reduction of high density lipoprotein cholesterol (HDC) is recognized as an important risk factor for coronary artery disease (CAD). We now show in approximately 1 in 20 males with proven atherosclerosis that an Asn291Ser mutation in the human lipoprotein lipase (LPL) gene is associated with significantly reduced HDL levels (P = 0.001) and results in a significant decrease in LPL catalytic activity (P < 0.0009). The relative frequency of this mutation increases in those patients with lower HDL cholesterol levels. In vitro mutagenesis and expression studies confirm that this change is associated with a significant reduction in LPL activity. Our data support the relationship between LPL activity and HDL-C levels, and suggest that a specific LPL mutation may be a factor in the development of atherosclerosis.

Adult↗
PubMed1995

A frequently occurring mutation in the lipoprotein lipase gene (Asn291Ser) contributes to the expression of familial combined hyperlipidemia.

We performed denaturing gradient gel electrophoresis (DGGE) of exons 4, 5, 6 and their exon-intron boundaries of the LPL-gene in 169 unrelated male patients suffering from familial combined hyperlipidemia (FCH). Twenty patients were found to carry a nucleotide substitution in exon 6. Sequence and PCR/digestion analysis revealed one common mutation (Asn291Ser) in all these cases. This mutation was talso present in 215 male controls, albeit at a lower frequency than in FCH patients (10/215 = 4.6% vs. 20/169 = 11.8%; p < 0.02). Analysis of lipid, lipoprotein and apolipoprotein levels demonstrated an association between the presence of this Asn291Ser substitution and decreased HDL-cholesterol (0.94 +/- 0.31 vs. 1.12 +/- 0.26 mmol/l; p < 0.04) in our controls. FCH patients carrying this mutation showed decreased HDL-cholesterol (0.75 +/- 0.16 vs. 0.95 +/- 0.36 mmol/l; p = 0.05) and increased triglyceride levels (5.96 +/- 4.12 vs. 3.48 +/- 1.78 mmol/l; p < 0.005) compared to non-carriers. The high triglyceride and low HDL-cholesterol phenotype in carriers of this substitution was most obvious when BMI exceeded 27 kg/m2. Our study of male FCH patients revealed the presence of a common mutation in the LPL-gene that is associated with lipoprotein abnormalities, indicating that defective LPL is at least one of the factors contributing to the FCH-phenotype.

Asparagine↗
PubMed1994

Analysis of DNA changes in the LPL gene in patients with familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCHL) is a common lipid disorder characterized by an increase in cholesterol and/or triglyceride levels in multiple individuals of the same family. Prior reports document a decreased activity of lipoprotein lipase (LPL) in FCHL, and studies of the role of LPL in the remodeling of nascent lipoproteins suggest that disturbances in LPL function could underlie FCHL. We studied the LPL gene in 31 unrelated individuals with FCHL. A total of 25 DNA changes (13 "silent" substitutions and 12 DNA changes resulting in amino acid substitutions) were detected in 16 patients. Three new exonic polymorphisms as well as a previously described Ser447-->stop and an Asp9-->Asn substitution were seen with similar frequency on control and FCHL chromosomes. Two novel DNA changes resulting in an Asp21-->Val and an His44-->Tyr substitution were seen in only two FCHL individuals. In vitro studies showed no effect of these mutations on LPL catalytic activity. LPL mutations impairing catalytic activity did not represent a significant factor leading to FCHL in this population. Variations in any portion of the coding region of the LPL gene affecting other functions besides catalysis are not a frequent cause of FCHL.

Adult↗
PubMed1989

Morphologic prognostic factors of malignant mixed müllerian tumor of the uterus: a clinicopathologic study of 58 cases.

Sixty-one patients with malignant mixed müllerian tumor (MMMT) of the uterus were seen at L'Hôtel-Dieu de Québec between 1950 and 1986, and the histopathologic material was available for review in 58 cases. Of the morphologic parameters studied, the histologic grade of both epithelial and mesenchymal components correlated with the initial stage. Patients with stages I and II disease had a significantly better survival rate than those with stages III and IV (P less than 0.006). Twenty-five patients with a minimum follow-up of two years were initially stage I or II. All six patients of this subgroup with an epithelial component of serous carcinoma type were dead of their disease at 2 yr. Although not statistically significant, tumor necrosis, the mode of tumor invasive (pushing and infiltrative), and the ratio of epithelial to mesenchymal components tended to influence the outcome. The mitotic rate, the type of mesenchymal components, and vascular and myometrial invasion were of no prognostic significance. We conclude that the outcome of patients with uterine MMMT is mainly influenced by the initial stage and the type of epithelial component. The influence of tumor necrosis, the ratio of epithelial to mesenchymal component, and the mode of tumor invasion deserve further studies.

Adult↗
PubMed1982

[Psychiatric exam under court order apropos of patients who refuse to submit to a psychiatric exam].

In this retrospective study 52 patients who had not committed any offence were examined against their will by Court order in the emergency department of a psychiatric hospital. They were compared with a control group of patients reflecting the usual clientele attending without compulsion the emergency department of the same hospital. This research reveals it is the immediate family rather than medico-social agencies that took the initiative in arranging the Court-ordered psychiatric examination. Such patients were no different than the usual patients seen in the emergency department as to age, sex, marital status and past psychiatric history. It was at the level of symptomatology and diagnosis that such patients differed from patients in the control group. The patients refusing to submit to a psychiatric examination not only were more agitated and aggressive, but they were more disorganized, more delusional, and had more hallucinations than the patients in the control group. They were in fact grossly psychotic patients with paranoid and manic features dominating the clinical picture. Our study demonstrated that as far as Montreal is concerned flagrant abuse of civil rights is far more the exception than the rule. Furthermore, if society had to abandon compulsory measures in some cases, it would be the seriously mentally ill who would suffer.

Adolescent↗