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N Cohen

Publications and source records attributed to N Cohen.

At least 127 records · Page 7Linked to original sources
PubMed1996

[The PROGENE study, the French project of genetic analysis of familial prostatic cancer: recruitment and analysis].

OBJECTIVES: To initiate a genetic linkage study in order to localize one or several predisposition gene(s) for hereditary prostatic cancer (PC), as various epidemiological studies have demonstrated a possible family aggregation in about 25% of cases. A family segregation study [14] has also shown that a genetic predisposition, with autosomal dominant transmission and high penetrance (88% at 85 years) could be responsible for 9% of all PC. METHODS: A national collection of families with at least 2 cases of PC allowed: 1) identification of families with hereditary forms of PC, 2) creation of a constitutional DNA bank after collecting blood samples from subjects belonging to these families, and 3) a simulation study of genetic linkage analysis prior to microsatellite genotyping. RESULTS: From July 1994 to September 1995, we included 67 families (180 cases of PC). Another 45 families are currently being included. 24 of these 67 families (89 PC, 54 survivors) satisfied at least one of the criteria defined in the study by CARTER et al. for hereditary forms of familial PC. Two families were also included as the 3 patients with PC were second degree relatives. A total of 26 families therefore presented a hereditary form, 18 of which (73 PC, 46 survivors) were considered to be informative for a genetic linkage study (lod score = 4 for theta = 0.001 with an 8 allele marker). The constitutional DNA of 271 individuals of these informative families was extracted from circulating cells obtained from blood samples, immortalized lymphocytes, and the genotyping was initiated for 216 microsatellite markers distributed throughout the genome, an average of every 20 cM. CONCLUSION: Although the recruitment allowed us to identify many informative families for an inherited risk of PC, the predictive study suggested a high probability for localization of a predisposition gene by genetic linkage analysis. It would therefore be possible to identify, within the families concerned, the subjects carrying the genetic anomaly and consequently at high-risk of PC. Finally, the demonstration of the locus would allow cloning and identification of the gene (s) involved.

Female↗
PubMed1996

Early results of infrageniculate arterial reconstruction using cryopreserved homograft saphenous conduit (CADVEIN) and combination low-dose systemic immunosuppression.

BACKGROUND: The search continues for the ideal conduit for infrageniculate arterial reconstructions when the autogenous vein is unsuitable or unavailable. Based on experimental observations in our laboratory demonstrating improvement in canine cryopreserved allograft vein patency using systemic immunosuppression (Imsup), and the remarkable clinical success achieved in older (greater than 60 years of age) solid organ transplant recipients using combination low-dose Imsup, we studied the effects of Imsup on patency of cryopreserved homograft saphenous vein (CADVEIN) used for infrageniculate arterial reconstructions. STUDY DESIGN: Under the Institutional Review Board protocol, 21 infrageniculate CADVEIN grafts were placed in 19 patients between July 1993 and August 1994 for limb salvage when autogenous veins were unavailable. An immunopharmacologic protocol consisting of low-dose cyclosporine A, azathioprine, prednisone, warfarin, aspirin, and vasodilators given orally was instituted. For various reasons, 15 patients in group 1 received Imsup; five patients never received Imsup, and one patient in group 2 received Imsup briefly. Follow-up examinations were completed using the time range of six to 18 months (mean, eight plus or minus one month). RESULTS: One patient died (5.3 percent) 30 days after emergency combined venous graft and bilateral CADVEIN bypass. The actuarial 12-month primary patency in group 1 was 59.4 percent compared with 16.7 percent in group 2 (p < 0.015, log-rank test). Cellular rejection was typically seen in explanted CADVEIN. Systemic morbidity related to Imsup was minimal. The CADVEIN morbidity rate was significant: three graft aneurysms and four early graft ruptures. Major amputations were necessary in eight of 12 patients with graft closure. CONCLUSIONS: The data suggest that Imsup significantly improves CADVEIN patency with limited systemic morbidity; however, complications related to the conduit itself occurred with greater frequency and cause greater morbidity than when the autogenous veins were used. Much has yet to be learned regarding the preservation characteristics of CADVEIN and the immunologic interactions in patients receiving CADVEIN grafts, before further clinical use of this conduit can be recommended.

Adult↗
PubMed1996

Effect of furosemide oral solution versus furosemide tablets on diuresis and electrolytes in patients with moderate congestive heart failure.

Oral furosemide solution was claimed to produce a greater diuretic response than furosemide tablets in patients with congestive heart failure. The aim of this study was to assess this observation and to further investigate the effects on the electrolyte balance. We compared the effects of oral furosemide in tablets versus oral furosemide solution on serum levels as well as on 4- and cumulative 24-hour urinary volume and sodium, potassium, calcium, magnesium and zinc excretions in 10 patients with moderate congestive heart failure due to ischemic heart disease. Oral furosemide (40-80 mg) was given at the usual once-daily dosage. No change in serum electrolyte levels has been found. All urinary parameters, except zinc, were significantly greater during the first 4 h following oral solution as compared with tablets (volume p < 0.001, sodium p < 0.001, potassium p < 0.05, calcium p < 0.003, magnesium p < 0.05). However, after 24 h, significant differences were found in urinary volume (p < 0.03) and sodium excretion (p < 0.004) only. We conclude that: (1) oral furosemide solution provides a more potent 24-hour diuretic and natriuretic effect than an identical dosage in tablet form, without entailing greater cumulative urinary losses of potassium, calcium, magnesium, and zinc; (2) following the first 4 h of furosemide solution, brisk diuresis, kaliuresis, and magnesiuria are produced, and (3) despite the urinary losses, serum electrolytes remained within normal limits at 4 and 24 h.

Aged↗
PubMed1995

Gln-Arg192 polymorphism of paraoxonase and coronary heart disease in type 2 diabetes.

Paraoxonase is a high-density-lipoprotein-associated enzyme capable of hydrolysing lipid peroxides. Thus it might protect lipoproteins from oxidation. It has two isoforms, which arise from a glutamine (A isoform) to arginine (B isoform) interchange at position 192. The relevance of this polymorphism to coronary heart disease (CHD) in non-insulin-dependent diabetic patients was investigated in case-control study. Of the 434 patients, 171 had confirmed coronary artery disease; the other 263 had no history of such disease. The B allele and AB+BB genotypes were associated with an increased risk of coronary heart disease. Compared with subjects homozygous for the A allele (AA genotype), the odds ratio of CHD for subjects homozygous for the B allele was 2.5 (95% CI 1.2-5.3) and that for those heterozygous for the B allele was 1.6 (95% CI 1.1-2.4), suggesting a codominant effect on cardiovascular risk. When subjected to multivariate analysis, the B allele remained significantly associated with CHD (odds ratio 1.94, p = 0.03). The paraoxonase gene polymorphism is thus an independent cardiovascular risk factor in non-insulin-dependent diabetic patients. A possible explanation for this finding is that activity of the paraoxonase B isotype does not protect well against lipid oxidation, a major atherogenic pathway.

Arginine↗
PubMed1995

Oral vanadyl sulfate improves hepatic and peripheral insulin sensitivity in patients with non-insulin-dependent diabetes mellitus.

We examined the in vivo metabolic effects of vanadyl sulfate (VS) in non-insulin-dependent diabetes mellitus (NIDDM). Six NIDDM subjects treated with diet and/or sulfonylureas were examined at the end of three consecutive periods: placebo for 2 wk, VS (100 mg/d) for 3 wk, and placebo for 2 wk. Euglycemic hyperinsulinemic (30 mU/m2.min) clamps and oral glucose tolerance tests were performed at the end of each study period. Glycemic control at baseline was poor (fasting plasma glucose 210 +/- 19 mg/dl; HbA1c 9.6 +/- 0.6%) and improved after treatment (181 +/- 14 mg/dl [P < 0.05], 8.8 +/- 0.6%, [P < 0.002]); fasting and post-glucose tolerance test plasma insulin concentrations were unchanged. After VS, the glucose infusion rate during the clamp was increased (by approximately 88%, from 1.80 to 3.38 mg/kg.min, P < 0.0001). This improvement was due to both enhanced insulin-mediated stimulation of glucose uptake (rate of glucose disposal [Rd], +0.89 mg/kg.min) and increased inhibition of HGP (-0.74 mg/kg.min) (P < 0.0001 for both). Increased insulin-stimulated glycogen synthesis (+0.74 mg/kg.min, P < 0.0003) accounted for > 80% of the increased Rd after VS, and the improvement in insulin sensitivity was maintained after the second placebo period. The Km of skeletal muscle glycogen synthase was lowered by approximately 30% after VS treatment (P < 0.05). These results indicate that 3 wk of treatment with VS improves hepatic and peripheral insulin sensitivity in insulin-resistant NIDDM humans. These effects were sustained for up to 2 wk after discontinuation of VS.

Administration, Oral↗
PubMed1995

Counterregulation of hypoglycemia. Skeletal muscle glycogen metabolism during three hours of physiological hyperinsulinemia in humans.

We examined the role of skeletal muscle in counterregulation of hypoglycemia (3.4 +/- 0.1 mmol/l) in 12 nondiabetic individuals (age 26 +/- 1 years, body mass index 24.2 +/- 0.7 kg/m2) during physiological hyperinsulinemia (280 +/- 25 pmol/l) compared with euglycemia (4.8 +/- 0.1 mmol/l). During hypoglycemia, hepatic glucose output (3-[3H]-glucose) was greater (7.72 +/- 2.72 mumol.kg-1.min-1, P < 0.01), glucose uptake was approximately 49% lower (21.20 +/- 3.55 mumol.kg-1.min-1, P < 0.005), and glucose clearance was reduced (P < 0.002) compared with euglycemia. Rates of flux of plasma-derived glucosyl units through glycolysis were similar in the two experiments, while glycogen synthetic rates were significantly reduced during hypoglycemia (P < 0.01) and accounted entirely for the reduction in glucose disposal. The insulin-induced activation of skeletal muscle glycogen synthase (reflected by Km decline by approximately 50% from 0.408 +/- 0.056 mmol/l and fractional velocity increase by approximately twofold from 21.8 +/- 2.7%) was completely abolished in hypoglycemia. In concert, glycogen phosphorylase activity increased during hypoglycemia by approximately 40% (P = 0.0001). Hypoglycemia resulted in seven- to eightfold increments in plasma epinephrine (P < 0.0001) and growth hormone (P < 0.001) and 40-60% increments in plasma glucagon (P < 0.005) and cortisol (P < 0.05). We conclude that, in this model of mild hypoglycemia of moderate duration, the majority of the glucose made available during the counterregulatory process (approximately 60-70%) is due to the limitation of glucose disposal, mostly via decreased glycogen synthetic activity in skeletal muscle.

Adult↗
PubMed1995

Age-related ANP release in response to acute vs. chronic sodium loading.

Atrial natriuretic peptide (ANP) levels were studied in young (2-week-old) and old (age 20 months) rats following acute (20 mL/kg bolus of normal saline i.v.) vs. chronic sodium loading (high-salt diet for 21 days). In both groups serum ANP rose significantly 1 h post i.v. loading. However, the increment was greater in the old animals. On chronic sodium load, in the young group, ANP rose significantly on days 3 and 7, subsequently declining to baseline. In the old animals, no increase in ANP was noted throughout the chronic experiment. Twenty-four-hour urinary sodium excretion was similar in the two groups following acute or chronic salt load. The results suggest that: (1) The old kidney requires a greater ANP stimulus to excrete a given acute i.v. sodium load. (2) The relatively diminished elasticity of the old heart plays a major role in the exaggerated ANP release in response to a bolus i.v. load of saline. (3) The role of ANP in maintaining homeostatic renal sodium excretion during short-term sodium oral loading is different in the two age groups.

Aging↗
PubMed1994

Insertion/deletion polymorphism of the angiotensin-converting enzyme gene is strongly associated with coronary heart disease in non-insulin-dependent diabetes mellitus.

Non-insulin-dependent diabetes mellitus (NIDDM) is considered a model of premature atherosclerosis with a strong genetic component. We have investigated the role of angiotensin-converting enzyme (ACE; EC 3.4.15.1) gene in 316 unrelated NIDDM individuals, 132 who had myocardial infarction or significant coronary stenoses and 184 with no history of coronary heart disease (CHD). A deletion-polymorphism in the ACE gene was recently reported to be associated with myocardial infarction especially in people classified as low risk. Here we report that the D allele of the ACE gene is a strong and independent risk factor for CHD in NIDDM patients. The D allele is associated with early-onset CHD in NIDDM, independently of hypertension and lipid values. A progressively increasing relative risk in individuals heterozygous and homozygous for the D allele was observed (odds ratios of 1.41 and 2.35, respectively; P < 0.007), suggesting a codominant effect on the cardiovascular risk. The percentage of CHD attributable to the ACE deletion allele was 24% in this NIDDM population. Identification of NIDDM patients carrying this putative CHD-susceptibility genotype would help early detection and treatment of CHD.

Alleles↗
PubMed1994

[Bronchiolitis obliterans organizing pneumonia].

Bronchiolitis obliterans organizing pneumonia (BOOP) is an uncommon condition of unknown etiology which often responds to corticosteroids. It is characterized by cough, patchy pulmonary infiltrations and intra-alveolar organizing fibrosis. We report a 45-year-old man and a 70-year-old woman with BOOP and elevated liver enzymes. Corticosteroid therapy led to complete recovery.

Adrenal Cortex Hormones↗
PubMed1994

Similar immune response to nonlethal infection with herpes simplex virus-1 in sensitive (BALB/c) and resistant (C57BL/6) strains of mice.

Previous investigations have demonstrated a strain-associated differential susceptibility to herpes simplex virus-1 (HSV-1) infection in mice; C57BL/6 mice are more resistant to infection than BALB/c mice. Despite considerable research dealing with the immune response to HSV-1, relatively little attention has been paid to differences in immune responses between strains with different sensitivities to the virus. Here we report that immune responses (i.e., cytokine profiles, CTL activity, serum antibody, and natural killer cell activity) following footpad infection with a sublethal dose of HSV-1 do not substantially differ between the two strains. It is notable that C57BL/6 mice are also more resistant than BALB/c mice to other pathogens, including Leishmania, and this resistance is associated with a predominant TH1 response in C57BL/6 mice versus a predominant TH2 response in BALB/c mice. However, unlike several other pathogens, the increased susceptibility to HSV-1 infection of BALB/c mice, compared to C57BL/6 mice, does not appear to involve an obvious difference in the TH1 vs TH2 dominance of the immune response to this virus.

Animals↗