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  • 1
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Journal of the American Chemical Society 59 (1937), S. 1178-1182 
    ISSN: 1520-5126
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-041X
    Keywords: Parthenogenesis ; Mouse chimeras ; Proliferation ; Differentiation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Parthenogenetic cells are lost from fetal chimeras. This may be due to decreased proliferative potential. To address this question, we have made use of combined cell lineage and cell proliferation analysis. Thus, the incorporation of bromodeoxyuridine in S-phase was determined for both parthenogenetic and normal cells in several tissues of fetal day 13 and 17 chimeras. A pronounced reduction of bromodesoxyuridine incorporation by parthenogenetic cells at both developmental stages was only observed in cartilage. In brain, skeletal muscle, heart and intestinal epithelium, this reduction was either less pronounced or observed only at one of the developmental stages analysed. No difference between parthenogenetic and normal cells was observed in epidermis and ganglia. Our results show that a loss of proliferative potential of parthenogenetic cells during fetal development contributes to their rapid elimination in some tissues. The analysis of the fate of parthenogenetic cells in skeletal muscle and cartilage development demonstrated different selection mechanisms in these tissues. In skeletal muscle, parthenogenetic cells were largely excluded from the myogenic lineage proper by early post-midgestation. In primary hyaline cartilage, parthenogenetic cells persisted into adulthood but were lost from cartilages that undergo ossification during late fetal development.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 39 (1996), S. 368-370 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Keywords Type I (insulin-dependent) diabetes ; quality of care ; diabetes education ; late complications ; HbA1c ; hypoglycaemia ; diet ; cardiovascular complications ; quality of life.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The objective of this study was to assess the degree of diabetes care and education achieved for Type I (insulin-dependent) diabetes mellitus at the community level in relation to social status and to elucidate potential pathways that mediate any social class gradient. A population-based sample of 684 adults with Type I diabetes (41 % women, mean ± SD age 36 ± 11, diabetes duration 18 ± 11 years) in the district of North-Rhine (9.5 million inhabitants), Germany, were examined in their homes using a mobile ambulance. Results: HbA1c (normal 4.3–6.1 %) 8.0 ± 1.5 %, incidence of severe hypoglycaemia (injection of glucose or glucagon) 0.21 cases per patient-year; 62 % of patients had participated in a structured group treatment and teaching programme for intensification of insulin therapy; 70 % used 3 or more insulin injections per day, 9 % were on continuous subcutaneous insulin infusion; 91 % reported to have had measurements of HbA1c during the preceding year, and 80 % to have had an examination of the retina by an ophthalmologist. Care was insufficient with respect to the quality of blood pressure control (70 % of patients on antihypertensive drugs had blood pressure values ≥ 160/95 mmHg), patient awareness of proteinuria/albuminuria (27 % of patients had not heard about it) and prevention of foot complications (only 42 % with a diabetes duration over 10 years had remembered to have a foot examination during the preceding 12 months). There was a pronounced social gradient with respect to micro- and macrovascular complications (prevalence of overt nephropathy 7 vs 20 % for highest vs lowest quintiles of social class [OR 3.5, 95 % CI 1.6–7.5, p = 0.002]) and diabetes-specific quality of life. HbA1c, blood pressure and smoking accounted for part of the association between social class and microvascular complications. The social class gradient was not due to inequality to access to health services, but to lower acceptance among low social class patients of preventive and health maintaining behaviour. In conclusion, achieved standards of care are high with respect to the implementation of intensified treatment regimens, the level of patient education achieved, treatment control and eye care, whereas areas for improvement are blood pressure control and preventive measures for foot care. A substantial social gradient in diabetes care persists despite equal access of patients to health services. [Diabetologia (1998) 41: 1139–1150]
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Diabetes mellitus ; nephropathy ; pregnancy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to improve the basis upon which to advise women with diabetic nephropathy about pregnancy, we studied the effect of diabetic nephropathy on the course of pregnancy, perinatal out-come, infant development and long-term outcome of the mothers. All pregnancies of women with diabetic nephropathy (defined as proteinuria 〉400 mg/day (n=26), creatinine clearance 〈80 ml/min and hypertension in the first trimester (n=10)) followed at our centre from 1982 to 1992 were identified (34 White class F and 2 White class T) and the women and their children re-examined in the spring 1993. From the first to the third trimester the percentage of women with proteinuria over 3 g/day increased from 14 to 53% and those treated with anti-hypertensive medication from 53 to 97%. There were no intrauterine or perinatal deaths, but one child died suddenly 4 weeks postpartum. Of 36 new-borns (gestational week at birth 36(3), birth weight 2384(834) g)), 11 were born before week 34 and 8 had respiratory distress syndrome. Renal function in the first trimester, diastolic blood pressure in the third trimester and an HbA1c above normal were predictive of gestational age at delivery and low birth weight (stepwise regression analysis). At follow-up of the children (n=35, age 4.5 (0.4–10) years) the majority (n=27) were normally developed but seven had psychomotor retardation (four of them major). One child had a severe motor retardation due to a congenital anomaly. At follow up, 21 of the 29 mothers had preserved renal function (creatinine 1.3 (0.8–4.3) mg/dl and 8 had developed end stage renal disease and required dialysis (2 of whom were White class T) within 3 (1–9) years postpartum. Of those, 4 women (3 White F and 1 White T) had died. Pregnancy did not seem to specifically accelerate the rate of decline of renal function. In women with diabetic nephropathy perinatal mortality can be prevented but perinatal and long-term infant morbidity remains elevated. Women with severely impaired renal function before pregnancy are at risk for serious morbidity when their children are still young. Improvement might be made if all women were to receive specialized care and counselling before, throughout and after pregnancy.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 39 (1996), S. 77-81 
    ISSN: 1432-0428
    Keywords: Diabetic nephropathy ; diabetic autonomic neuropathy ; QT interval ; hypertension ; mortality
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Patients with diabetic nephropathy face an increased risk of dying due to cardiac causes. The aim of this follow-up trial was to describe the association between the length of the QT interval, as a marker of myocardial electrical stability, and the risk of death in insulin-dependent (IDDM) diabetic patients with overt diabetic nephropathy. A consecutive sample of 85 IDDM patients with overt diabetic nephropathy (i. e. persistent proteinuria ≥ 500 mg/24 h) were followed-up until death or for a period of 5–13 years. QT intervals were measured once at baseline in a 12-lead ECG and corrected for heart rate (QTc). During the follow-up period 33 patients (39%) died. In the Cox proportional hazards model independent predictors of death were age (p=0.0007), the length of the maximum QTc period (p=0.0049), presence of autonomic neuropathy (p=0.0068), diabetes duration (p=0.0163) and RR variation (p=0.0395). In conclusion, in nephropathic IDDM patients QT prolongation is associated with an increased mortality risk which is independent of the presence of autonomic neuropathy. Further studies are needed to determine whether this risk might be reduced by therapeutic interventions.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Key words Glibenclamide, glyburide, sulphonylurea compounds, AG-EE 623 ZW, dose-response, time-action profiles, pharmacokinetics, glucose clamp technique.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin and glucose responses to glibenclamide were studied in comparison to a novel non-sulphonylurea drug (AG) by means of the euglycaemic clamp technique. Nine fasting male subjects were connected to a Biostator and 1.75, 3.5 or 7.0 mg glibenclamide or 1.0, 2.0 or 4.0 mg AG were given and blood glucose concentrations were clamped at 10 % below basal values. Glucose infusion rates were registered over 10 h after administration of the tablet. Maximal glucose infusion rates after glibenclamide were 40 % higher compared to AG (1.75 vs 1.0 mg, 3.5 vs 2.0 mg, 7.0 vs 4.0 mg, respectively) and were reached after 3–3.5 h for all doses. After glibenclamide, area under the glucose infusion curves and maximal incremental serum insulin responses were higher by 25–40 % and by 30 % compared to AG when low, medium and high doses of each drug were tested. However, a linear dose relationship was obtained for both drugs when the glucose infusion rate was plotted against the area under the insulin curve. In fact, both drugs were equipotent on a molecular weight basis. The hypoglycaemic index of both drugs (integrated glucose infusion rate divided by integrated insulin release) expressed per µmol of drug revealed a dose-dependent and parallel inverse curvilinear relation to increasing doses. This methodological approach allowed us to quantify and compare the metabolic effects of oral hypoglycaemic agents under standardised experimental conditions. [Diabetologia (1994) 37: 703–707]
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Glibenclamide ; glyburide ; sulphonylurea ; compounds ; AG-EE 623 ZW ; dose-response ; time-action profiles ; pharmacokinetics ; glucose clamp technique
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin and glucose responses to glibenclamide were studied in comparison to a novel non-sulphonylurea drug (AG) by means of the euglycaemic clamp technique. Nine fasting male subjects were connected to a Biostator and 1.75, 3.5 or 7.0 mg glibenclamide or 1.0, 2.0 or 4.0 mg AG were given and blood glucose concentrations were clamped at 10% below basal values. Glucose infusion rates were registered over 10 h after administration of the tablet. Maximal glucose infusion rates after glibenclamide were 40% higher compared to AG (1.75 vs 1.0 mg, 3.5 vs 2.0 mg, 7.0 vs 4.0 mg, respectively) and were reached after 3–3.5 h for all doses. After glibenclamide, area under the glucose infusion curves and maximal incremental serum insulin responses were higher by 25–40% and by 30% compared to AG when low, medium and high doses of each drug were tested. However, a linear dose relationship was obtained for both drugs when the glucose infusion rate was plotted against the area under the insulin curve. In fact, both drugs were equipotent on a molecular weight basis. The hypoglycaemic index of both drugs (integrated glucose infusion rate divided by integrated insulin release) expressed per μmol of drug revealed a dose-dependent and parallel inverse curvilinear relation to increasing doses. This methodological approach allowed us to quantify and compare the metabolic effects of oral hypoglycaemic agents under standardised experimental conditions.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0428
    Keywords: Key words Diabetes mellitus ; nephropathy ; pregnancy.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to improve the basis upon which to advise women with diabetic nephropathy about pregnancy, we studied the effect of diabetic nephropathy on the course of pregnancy, perinatal outcome, infant development and long-term outcome of the mothers. All pregnancies of women with diabetic nephropathy (defined as proteinuria 〉 400 mg/day (n = 26), creatinine clearance 〈 80 ml/min and hypertension in the first trimester (n = 10) ) followed at our centre from 1982 to 1992 were identified (34 White class F and 2 White class T) and the women and their children re-examined in the spring 1993. From the first to the third trimester the percentage of women with proteinuria over 3 g/day increased from 14 to 53 % and those treated with antihypertensive medication from 53 to 97 %. There were no intrauterine or perinatal deaths, but one child died suddenly 4 weeks postpartum. Of 36 newborns (gestational week at birth 36(3), birth weight 2384(834) g) ), 11 were born before week 34 and 8 had respiratory distress syndrome. Renal function in the first trimester, diastolic blood pressure in the third trimester and an HbA1c above normal were predictive of gestational age at delivery and low birth weight (stepwise regression analysis). At follow-up of the children (n = 35, age 4.5 (0.4–10) years) the majority (n = 27) were normally developed but seven had psychomotor retardation (four of them major). One child had a severe motor retardation due to a congenital anomaly. At follow up, 21 of the 29 mothers had preserved renal function (creatinine 1.3 (0.8–4.3) mg/dl and 8 had developed end stage renal disease and required dialysis (2 of whom were White class T) within 3 (1–9) years postpartum. Of those, 4 women (3 White F and 1 White T) had died. Pregnancy did not seem to specifically accelerate the rate of decline of renal function. In women with diabetic nephropathy perinatal mortality can be prevented but perinatal and long-term infant morbidity remains elevated. Women with severely impaired renal function before pregnancy are at risk for serious morbidity when their children are still young. Improvement might be made if all women were to receive specialized care and counselling before, throughout and after pregnancy. [Diabetologia (1995) 38: 227–235].
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: Dietary sodium ; diabetes mellitus ; blood pressure ; nephropathy ; body volumes ; exchangeable body sodium ; renin-angiotensin-aldosterone system ; atrial natriuretic peptide ; noradrenaline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The objectives of the study were to assess the effects of moderate sodium restriction on blood pressure in insulin-dependent diabetic (IDDM) patients with nephropathy and high normal or mildly hypertensive blood pressure (primary objective), and to document possible associated changes of exchangeable body sodium, body volumes, components of the renin-angiotensin-aldosterone system, atrial natriuretic peptide, and catecholamines (secondary objective). Sixteen patients with untreated systolic blood pressure ≥ 140 〈160 mmHg and/or diastolic blood pressure ≥ 85 〈100 mmHg were included in a double-blind, randomized, placebo-controlled trial. After a 4-week run-in period on their usual diet and a 2-week dietary training period to reduce sodium intake to about 90 mmol/day, eight patients received 100 mmol/day sodium supplement (group 2) and eight patients a matching placebo (group 1) for 4 weeks while continuing on the reduced-sodium diet. Patients were examined at weekly intervals. Main response variables were mean values of supine and sitting systolic and diastolic blood pressure as measured in the clinic and by the patients at home. The differences in blood pressure between the beginning and the end of the blinded 4-week study period were calculated and the differences in changes between the two patient groups were regarded as the main outcome parameters. During the blinded 4-week study period, average urinary sodium excretion was 92±33 (mean ± SD) mmol/day in group 1 and 199±52 mmol/day in group 2 (p=0.0002). The differences in blood pressure changes between the two patient groups were 3.9(−1.2 to 9) mmHg [mean (95% confidence intervals)] for systolic home blood pressure, 0.9(−3.7 to 5.5) mmHg for diastolic home blood pressure, 4.9(−3.3 to 13.1) mmHg for clinic systolic blood pressure and 5.3(1 to 9.7 mmHg, p=0.02) for clinic diastolic blood pressure. Combining all patients, there were relevant associations between changes of urinary sodium excretion and blood volume (Spearman correlation coefficient r=0.57), blood pressure and angiotensin II (diastolic: r=−0.7; systolic: r=−0.48), and exchangeable body sodium and renin activity (r=−0.5). In conclusion, in this study of IDDM patients with nephropathy and high normal or mildly hypertensive blood pressure, a difference in sodium intake of about 100 mmol/day for a period of 4 weeks led to a slight reduction of clinic diastolic blood pressure. Studies including larger numbers of patients with various stages of nephropathy and hypertension are needed to definitely clarify the effects of sodium restriction in IDDM.
    Type of Medium: Electronic Resource
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