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  • 1
    Keywords: CANCER ; MODEL ; MODELS ; FOLLOW-UP ; RISK ; METABOLISM ; INDEX ; CARCINOGENESIS ; ASSOCIATION ; BREAST-CANCER ; NO ; hormone ; PLASMA ; NUMBER ; WOMEN ; OBESITY ; cancer risk ; ORAL-CONTRACEPTIVES ; cholesterol ; LIPOPROTEIN ; LOW-DENSITY-LIPOPROTEIN ; case-control studies ; ABNORMALITIES ; BODY ; DIABETES-MELLITUS ; EPIC ; European Prospective Investigation into Cancer and Nutrition ; nutrition ; ENDOMETRIAL CANCER ; RELATIVE RISK ; REGRESSION-MODELS ; CLUSTER ; POSTMENOPAUSAL WOMEN ; MASS INDEX ; MASSES ; BODIES ; ONCOLOGY ; case control study ; case-control study ; REGRESSION ; ASSOCIATIONS ; ENDOMETRIAL ; RE ; INCREASE ; BODY-SIZE ; PHYSICAL-ACTIVITY ; LEVEL ; case control studies ; INTERVAL ; metabolic syndrome ; HORMONES ; prospective ; UNIT ; CANCER-RISK ; C-PEPTIDE ; SET ; case control ; LOGISTIC-REGRESSION ; BODY-MASS ; BODY-MASS-INDEX ; lipid ; HDL-CHOLESTEROL ; LOW-DENSITY ; SERUM-CHOLESTEROL
    Abstract: To clarify the role of metabolic factors in endometrial carcinogenesis, we conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), and examined the relation between prediagnostic plasma lipids, lipoproteins, and glucose, the metabolic syndrome (MetS; a cluster of metabolic factors) and endometrial cancer risk. Among pre- and postmenopausal women, 284 women developed endometrial cancer during follow-up. Using risk set sampling, 546 matched control subjects were selected. From conditional logistic regression models, high-density lipoprotein cholesterol (HDL-C) levels were inversely associated with risk body mass index (BMI)-adjusted relative risk (FR) for top versus bottom quartile 0.61 (95% confidence intervals (CI) 0.38-0.97), P-trend= 0.02). Glucose levels were positively associated with risk (BMI-adjusted RR top versus bottom quartile 1.69 (95% Cl 0.99-2.90), P-trend, = 0.03), which appeared stronger among postmenopausal women (BMI-adjusted RR top versus bottom tertile 2.61 (95% Cl 1.46-4.66), P-trend=0.0006, P-heterogeneity=0.13) and never-users of exogenous hormones (P-heterogeneity=0-005 for oral contraceptive (OC) use and 0.05 for hormone replacement therapy-use). The associations of HDL-C and glucose with risk were no longer statistically significant after further adjustment for obesity-related hormones. Plasma total cholesterol, Low-density lipoprotein cholesterol (LDL-C), and triglycerides were not significantly related to overall risk. The presence of MetS was associated with risk (RR 2.12 (95% CI 1.51-2.97)), which increased with the number of MetS factors (P-trend=0.02). An increasing number of MetS factors other than waist circumference, however, was marginally significantly associated with risk only in women with waist circumference above the median (P-interaction=0-01). None of the associations differed significantly by fasting status. These findings suggest that metabolic abnormalities and obesity may act synergistically to increase endometrial cancer risk
    Type of Publication: Journal article published
    PubMed ID: 17914105
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  • 2
    Keywords: CANCER ; MODEL ; MODELS ; THERAPY ; FOLLOW-UP ; COHORT ; cohort studies ; EXPOSURE ; RISK ; RISKS ; INDEX ; ASSOCIATION ; NO ; hormone ; HEALTH ; WOMEN ; HORMONE REPLACEMENT THERAPY ; cancer risk ; FIBER ; MEASUREMENT ERROR ; DIET ; DIETARY ; FAT ; European Prospective Investigation into Cancer and Nutrition ; nutrition ; AUSTRALIA ; ENDOMETRIAL CANCER ; RELATIVE RISK ; dietary fiber ; insulin ; IGF-I ; ASSOCIATIONS ; ENDOMETRIAL ; THERAPIES ; ENERGY-INTAKE ; PHYSICAL-ACTIVITY ; LEVEL ; INTERVAL ; USA ; prospective ; INSULIN SENSITIVITY ; VARIABLES ; CANCER-RISK ; C-PEPTIDE ; FOODS ; Nutrition Assessment ; postmenopausal ; DIANA RANDOMIZED-TRIAL ; dietary carbohydrates ; endometrial neoplasms ; glycemic index ; IOWA WOMENS HEALTH
    Abstract: The associations of dietary total carbohydrates, overall glycemic index, total dietary glycemic load, total sugars, total starch, and total fiber with endometrial cancer risk were analyzed among 288,428 women in the European Prospective Investigation into Cancer and Nutrition cohort (1992-2004), including 710 incident cases diagnosed during a mean 6.4 years of follow-up. Cox proportional hazards models were used to estimate relative risks and 95% confidence intervals. There were no statistically significant associations with endometrial cancer risk for increasing quartile intakes of any of the exposure variables. However, in continuous models calibrated by using 24-hour recall values, the multivariable relative risks were 1.61 (95% confidence interval: 1.06, 2.45) per 100 g/day of total carbohydrates, 1.40 (95% confidence interval: 0.99, 1.99) per 50 units/day of total dietary glycemic load, and 1.36 (95% confidence interval: 1.05, 1.76) per 50 g/day of total sugars. These associations were stronger among women who had never used postmenopausal hormone therapy compared with ever users (total carbohydrates P-heterogeneity = 0.04). Data suggest no association of overall glycemic index, total starch, and total fiber with risk, and a possible modest positive association of total carbohydrates, total dietary glycemic load, and total sugars with risk, particularly among never users of hormone replacement therapy
    Type of Publication: Journal article published
    PubMed ID: 17670911
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  • 3
    Keywords: CANCER ; BLOOD ; Germany ; MODEL ; MODELS ; FOLLOW-UP ; RISK ; RISKS ; METABOLISM ; TISSUE ; TIME ; RISK-FACTORS ; BINDING ; CYCLE ; ASSOCIATION ; BREAST-CANCER ; hormone ; resistance ; PLASMA ; AGE ; WOMEN ; OBESITY ; risk factors ; NECROSIS-FACTOR-ALPHA ; cancer risk ; case-control studies ; nutrition ; TYPE-2 ; ENDOMETRIAL CANCER ; RELATIVE RISK ; ADIPOSE-TISSUE ; POSTMENOPAUSAL WOMEN ; insulin ; case-control study ; REGRESSION ; ENDOMETRIAL ; MENSTRUAL-CYCLE ; fat distribution ; LEVEL ; case control studies ; INTERVAL ; methods ; PHASE ; INSULIN-RESISTANCE ; metabolic syndrome ; HORMONES ; PREMENOPAUSAL ; prospective ; RISK-FACTOR ; CANCER-RISK ; type 2 diabetes ; C-PEPTIDE ; SET ; SERUM ADIPONECTIN ; BINDING PROTEIN-1 ; CIRCULATING ADIPONECTIN
    Abstract: Background: Adiponectin, an adipocytokine secreted by adipose tissue, is decreased in obesity, insulin resistance, type 2 diabetes, and polycystic ovary syndrome, all of which are well-established risk factors for endometrial cancer. Methods: We conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition to examine the relation between prediagnostic plasma adiponectin levels and endometrial cancer risk. Among pre- and postmenopausal women who were not currently using exogenous hormones, 284 women developed incident endometrial cancer during an average of 5.1 yr of follow-up. Using risk set sampling, 548 control subjects were selected, matched on center, age, menopausal status, phase of menstrual cycle, time of blood draw, and fasting status. Conditional logistic regression models were used to estimate relative risks and 95% confidence intervals. Results: Adiponectin levels were inversely associated with endometrial cancer risk [body mass index-adjusted relative risk for the top vs. bottom quartile = 0.56 (95% confidence interval 0.36-0.86), P-trend = 0.006]. There was evidence of a stronger inverse association among obese women than among nonobese women (P-heterogeneity = 0.03). The inverse association also appeared stronger for women who were postmenopausal or perimenopausal than premenopausal at baseline, but this was not statistically significantly heterogeneous (P-heterogeneity = 0.51). The association remained statistically significant after separate adjustment for other obesity-related physiological risk factors such as C-peptide, IGF binding protein-1, IGF binding protein-2, SHBG, estrone, or free testosterone but only marginally statistically significant after simultaneous adjustment for these factors. Conclusions: High circulating adiponectin levels are associated with reduced endometrial cancer risk, largely independent of other obesity-related risk factors
    Type of Publication: Journal article published
    PubMed ID: 17062769
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  • 4
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    German Medical Science; Düsseldorf, Köln
    In:  Hypertonie 2003; 27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga; 20031126-20031129; Bonn; DOC03hochV43 /20041111/
    Publication Date: 2004-11-12
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 5
    ISSN: 0303-7207
    Keywords: Catecholamine ; Glucagon ; Glucose ; Insulin ; Pyruvate kinase ; Thyroid
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1041
    Keywords: Ganciclovir ; Renal failure ; pharmacokinetics ; haemodialysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics of ganciclovir was evaluated in a 73-year old anuric, haemodialyzed patient given 1.25 mg·kg-1 at the end of each haemodialysis session, three times per week. A biexponential decrease in plasma ganciclovir was observed, with a peak concentration of 3.7 mg·1-1 followed by a steady state value of 2.6 mg·1-1 for almost 40 h. The total plasma clearance was 0.05 ml·min-1·kg-1, the volume of distribution at steady state was 0.61·kg-1, the elimination half life was 132 h, the area under curve was 372 μg·h·ml-1, the mean residence time was 190 h, and the percentage of ganciclovir cleared from plasma after a 5 h haemodialysis session was 52.1%. The simulated pharmacokinetics over one month, following the same scheme of administration, did not suggest marked accumulation of ganciclovir. These results were obtained after a reduction of 58% in the recommended dose in patients with impaired renal function.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1279-8517
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Keywords Hyperinsulinaemic clamp ; insulin receptor ; IRS-1 ; RT-PCR.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We investigated the regulation of the mRNA expression of the insulin receptor, insulin receptor substrate-1 (IRS-1) and p85α-phosphatidylinositol-3-kinase (PI-3K), three major actors of insulin action, in skeletal muscle from 10 healthy lean volunteers, 13 obese patients with Type II (non-insulin-dependent) diabetes mellitus and 7 non-diabetic obese subjects. The in vivo regulation by insulin was studied using a 3-h euglycaemic, hyperinsulinaemic clamp. There were no differences in the basal concentrations of the three mRNAs in skeletal muscle between groups. Insulin infusion produced a twofold reduction in insulin receptor substrate-1 mRNA expression in the three groups (p 〈 0.02). In contrast, insulin increased p85α-phosphatidylinositol-3-kinase mRNA expression in muscle from non-diabetic subjects ( + 98 ± 22 % in lean and + 127 ± 16 % in obese, p 〈 0.02) but this effect was totally impaired in Type II diabetic patients ( + 5 ± 12 %, NS). A similar defect in insulin action on p85α-phosphatidylinositol-3-kinase mRNA expression was observed in abdominal subcutaneous adipose tissue ( + 138 ± 25 %, p 〈 0.01 in lean and + 46 ± 14 %, p 〈 0.02 in obese and + 29 ± 11 %, NS in Type II diabetic patients). The lack of action of insulin on p85α-phosphatidylinositol-3-kinase mRNA in diabetic subjects was probably not due to a deleterious effect of hyperglycaemia since improvement of the glycaemic control for 10 days did not restore the response in muscle or in adipose tissue. This study provides evidence for a defect in the regulation by insulin of PI-3K gene expression in Type II diabetic patients, thus reinforcing the concept that alterations at the gene expression might be involved in the pathogeny of Type II diabetes. [Diabetologia (1999) 42: 358–364]
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0428
    Keywords: Stable isotope ; [13C] glucose ; mass spectrometry ; human ; oral glucose load ; gas chromatography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The use of 13C labelled glucose in human metabolic studies has been limited by the high cost of the tracer and the problems of measuring low 13C isotopic abundance in plasma glucose. In the present work we describe a new gas chromatograph-isotope ratio mass spectrometer allowing the measurement of a 0.001 atom % increase in 13C abundance over baseline, on a nanomole glucose sample. Studies were performed in rats and in human subjects. The rate of glucose appearance in 24 h fasted rats using D-[1-13C] glucose as tracer and analysed by this new method was found to be 10.4±0.7 mg·kg−1· min−1, a value 21% lower than that found using D-[6,6-2H2] glucose as tracer (13.1±1.1 mg· kg−1· min−1) analysed by classic gas chromatography-mass spectrometry. The new method was also used to trace, in combination with D-[6,6 2H2] glucose, the metabolic fate in human subjects of two oral glucose loads (0.5 g· kg·−1), 1 g· kg ·−1) labelled with 0.1% D-[U-13C] glucose. During the six hours following the glucose load, it was found that total glucose appearance was 0.97±0.04 g· kg·−1 and 1.2±0.04 g· kg·−1, exogenous glucose appearance was 0.51±0.02 g· kg·−1 and 0.84±0.04 g· kg·−1, endogenous glucose production was 0.44±0.04 g· kg·−1 and 0.35±0.06 g·kg·−1 after the 0.5 and 1 g·kg·−1 load respectively. These values are similar to those reported using glucose labelled with radioactive isotopes. These results show that reliable kinetic parameters of glucose metabolism can be determined, without health hazard, in humans, at low cost, using 13C labelled glucose analysed with a new gas chromatograph-isotope ratio mass spectrometer.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: Keywords Uncoupling protein-3 ; obesity ; fasting ; skeletal muscle ; thermogenesis.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Uncoupling protein-3 (UCP3) is a mitochondrial protein expressed in skeletal muscle, an important site of thermogenesis in humans. By uncoupling respiration from ATP synthesis, UCP3 might be involved in the control of energy expenditure. Two transcripts encoding long (UCP3L) and short (UCP3S) form are generated from the human UCP3 gene. UCP3S is predicted to encode a protein which lacks the C-terminus of UCP3L, a region which contains motifs critical for uncoupling activity. We have investigated the regulation of UCP3L and UCP3S mRNAs in lean and obese humans. A specific reverse transcription-competitive polymerase chain reaction assay was developed to separately quantify the two mRNAs. Each transcript represents half of total UCP3 mRNA in 16 vastus lateralis muscle samples. The amounts of UCP3L and UCP3S mRNAs did not differ between obese and lean subjects. The effect of fasting was studied in six lean and seven obese subjects maintained on a hypocaloric diet (1045 kJ/d) for 5 days. Calorie restriction results in an approximately threefold increase of UCP3L and UCP3S mRNA levels. The induction was similar in lean and obese subjects. The data suggest that there is no major alteration of UCP3 gene expression and regulation at the level of transcription and alternative splicing in skeletal muscle of obese subjects. [Diabetologia (1998) 41: 829–832]
    Type of Medium: Electronic Resource
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