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  • 1
    ISSN: 1432-1041
    Keywords: Digitoxin ; biological assay ; digitoxin absorption ; digitoxin elimination ; digitalis intoxication
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 73 patients on digitoxin maintenance medication a progressive increase of mean serum digitoxin activity was found with increasing dose. However, there were considerable variations within each group. Change of dose was followed by a new steady state level close to that predicted by zero order absorption-first order elimination kinetics of the drug. In atrial fibrillation the expected fall in ventricular rate was always observed with increasing serum concentration. No significant difference in serum level was found 24 h after identical peroral and intravenous doses had been given to different groups of patients. However, significantly higher serum values were found in normal subjects than in patients with heart disease after identical peroral treatment. This probably indicates poorer absorption by the patients. In 13 subjects, the estimated serum digitoxin half-lives were 3.7 to 11.3 days. These large differences may explain much of the variation in serum values found during steady state therapy. The elimination curves were in accordance with a first order drug kinetics. Only three patients with definite digitalis intoxication were seen, all of whom had high serum values which did not overlap patients without features of intoxication. The results showed that several patients on maintenance therapy were under-digitalized. It is hoped that this or similar methods may make it possible to adjust individual treatment to compensate for differences in absorption, distribution and elimination, and thereby to increase the benefits and decrease the risks of toxicity of digitoxin therapy.
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  • 2
    ISSN: 1432-1041
    Keywords: hypertension ; hypertensive therapy ; drug utilization ; therapeutic traditions ; international differences
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A questionnaire survey based on hypertension case histories was performed among a representative sample of 400 GP's and hospital doctors in Northern Ireland, Norway and Sweden, countries having markedly different utilization of antihypertensive drugs. We found a greater propensity to start antihypertensive drug treatment in Northern Ireland than in Norway and Sweden. This was true both in mild diastolic and isolated systolic hypertension. Yet the utilization of antihypertensive drugs in Sweden is about 60% higher than in Northern Ireland and 30% higher than in Norway. Swedish physicians preferred beta-blockers as their first choice to a greater extent than physicians in Northern Ireland and Norway who selected thiazides more often. In general, the choice of drugs agreed with the sales and prescribing patterns in the three countries. Besides providing more insight in therapeutic traditions the study indicates that the lower prescribing of antihypertensive drugs in Northern Ireland, and to some extent in Norway, compared to Sweden, might be due to differences in true or apparent morbidity.
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  • 3
    ISSN: 1432-1041
    Keywords: diabetes ; therapy ; antidiabetic drugs ; therapeutic traditions ; questionnaire survey ; drug utilization ; international differences
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A questionnaire survey was carried out to explore differences in the approach to treatment of patients with Type II diabetes between physicians in Northern Ireland, Norway and Sweden, and to discover to what extent it could account for the three-fold difference in drug use between the countries. A representative sample of 400 physicians in each country was asked to give their opinions on the choice of therapy for three model cases designed to cover the spectrum of treatment — from diet alone to insulin. Significantly more Swedish (65%) than Northern Irish (51%) and Norwegian (52%) doctors suggested diet alone for uncomplicated diabetes recently discovered in a middle aged, overweight man. For symptomatic diabetes in a 76 year old overweight woman with few retinal microaneurysms, the majority of physicians in all three countries suggested treatment with sulphonylureas. Biguanides were here a more common alternative in Northern Ireland than in Scandinavia. For suspected secondary treatment failure in a 63 year old woman with no signs of complications, insulin was suggested by 71% of the Norwegian doctors but only by 44 and 49% of those in Northern Ireland and Sweden, respectively. General practitioners tended to suggest oral treatment earlier and to maintain it longer than hospital physicians. The study has demonstrated significant differences in the approach to treatment of Type II diabetes mellitus between physicians in the three countries. However, the differences were more prominent in the choice of drugs than in the threshold of drug treatment. The results also fit with qualitative but not with quantitative differences in drug sales between the countries, suggesting that important differences may exist in the prevalence of clinically recognized Type II diabetes.
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  • 4
    ISSN: 1432-0428
    Keywords: Diabetic pregnancy ; perinatal mortality ; diabetic retinopathy ; respiratory distress syndrome ; birth weight ; delivery methods ; White classification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary During the years 1970–1977, 234 pregnant diabetics were treated in Oslo. A regimen of close metabolic and obstetric control was used. The total perinatal mortality was 4.3%, and 3.1% in 160 patients followed from before week 28. In 74% of patients mean blood glucose (determined 4 times daily) during the last 5–6 weeks of pregnancy was below 6 mmol/l and in only one patient above 8 mmol/l. There was a low incidence of ketoacidosis (5 patients), pyelonephritis (3 patients), and severe preeclampsia (1 patient), although mild to moderate preeclampsia occurred in 28 patients. Preeclampsia was not associated with foetal loss. Macrosomia was rare. Respiratory distress occurred in 33 infants, in most cases light to moderate. Two foetal deaths were associated with respiratory distress. Progression of retinopathy was frequent, and appearance of or progression of proliferative changes occurred in 15 patients with retinopathy before pregnancy. Loss of visual acuity was rare, and reading vision was not lost by any patients. Induced vaginal delivery has been used in half the deliveries during the last years, whereas Caesarean section was preferred during the first years. Mean duration of pregnancy at delivery has been 260 days, 256 days during the first four years, and 262 days during the last four.
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  • 5
    ISSN: 1432-0428
    Keywords: Diabetic pregnancy ; metabolic profile ; diabetes mellitus ; insulin therapy ; metabolic control ; glucagon ; cortisol ; growth hormone ; ketone bodies ; blood glucose ; blood lactate ; blood pyruvate ; plasma non-esterified fatty acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In 5 closely controlled pregnant diabetics (duration of pregnancy 237–266 days) and 5 pregnant non-diabetics (duration of pregnancy 210–278 days) 4-hourly blood samples were taken throughout a 24 h period and analyzed for blood glucose, lactate, pyruvate, 3-hydroxybutyrate and acetoacetate, plasma non-esterified fatty acids (NEFA), glucagon and cortisol. 24 h urine specimen was analyzed for total catecholamines and 4-hydroxy-3-methoxymandelic acid. There were few significant differences in concentrations of metabolites and hormones in the two groups at any time, although the variations about the mean was usually greater in the diabetics. Thus for blood glucose in diabetics, mean value was 4.4 mmol/l, coefficient of variation 43%; in non-diabetics 4.1 mmol/l and 10% respectively. Mean plasma 3-hydroxybutyrate in diabetics was 0.47 mmol/l, coefficient of variation 55%; in non-diabetics 0.44 mmol/l and 37% respectively. Plasma non-esterified fatty acid levels were significantly higher in the diabetics (0.47 mmol/l) than in the non-diabetics (0.26 mmol/l). Coefficients of variation were 46% and 33% respectively. Two conclusions can be drawn; first, when near normal mean values for blood glucose are achieved, other metabolite and hormone levels are also near normal; second, even when the available means for diabetic control, strict diet and insulin-mixtures twice daily, are used at their maximum, metabolism in diabetics is more unstable than in non-diabetics.
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  • 6
    ISSN: 1432-0428
    Keywords: Combined Pancreas ; Kidney ; Transplantation Glucose ; Metabolism Long-term
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Metabolic glucose control was followed in 36 patients at 12-month intervals for up to 5 years after a successful combined kidney and segmental duct-occluded pancreas transplantation. All recipients had normal blood glucose levels at each examination. HbA1 values, intravenous glucose tolerance test, C-peptide levels and C-peptide responses to glucagon stimulation were also, on average, within the normal range. Several individual patients had, however, abnormal values for these parameters. At most 46% had abnormal values for HbA1 and intravenous glucose tolerance test, up to 13% showed low C-peptide values and up to 46% of the stimulated C-peptide responses were inadequate at the different intervals. These parameters did not deteriorate with time. This was true both for the whole group of patients as well as for the 6 patients with a 5-year observation time evaluated separately. Despite these abnormalities in glucose metabolism, all patients remained normoglycaemic without need for exogenous insulin up to 5 years after transplantation. The long-term ability of duct-occluded segmental pancreatic grafts to preserve euglycaemia therefore seems to remain intact at least for 5 years.
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  • 7
    ISSN: 1432-0428
    Keywords: Type 1 diabetes ; interstitial colloid osmotic pressure ; plasma colloid osmotic pressure ; interstitial fluid volume ; plasma volume ; transcapillary escape rate of albumin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Plasma and subcutaneous colloid osmotic pressure, transcapillary escape rate of albumin, plasma volume and extracellular fluid volume were measured in 10 long-term Type 1 (insulin-dependent) diabetic patients without clinical nephropathy. Interstitial colloid osmotic pressure was reduced compared with normal subjects (12.9±3.0 versus 15.8±2.7 mmHg, p〈0.05) and the transcapillary colloid osmotic gradient increased (17.0±2.4 versus 12.8±2.7 mmHg, p〈 0.01). Plasma volume was in the normal range and interstitial fluid volume increased by approximately 21% compared with normal subjects (p〈0.01). Transcapillary escape rate of albumin was significantly increased compared with normal subjects (8.9±1.9 versus 5.1±1.6%/h, p〈 0.01). A negative correlation was found between the transcapillary colloid osmotic gradient and interstitial fluid volume (r=0.6, 0.01〈p〈0.05). These results suggest that the increased small vessel permeability in long-term diabetes leads to wash-out of interstitial proteins and the resulting increased transcapillary colloid osmotic gradient tends to preserve the plasma volume and to limit the tendency to increased interstitial fluid volume.
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  • 8
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 9
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 10
    ISSN: 1432-0428
    Keywords: Type 1 diabetes ; T-lymphocyte responses ; HLA-restriction ; mumps ; Coxsackie B4
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To study the relationships between the responses to viral antigens and the HLA-DR3 and -DR4 associations in Type 1 (insulin-dependent) diabetes mellitus, the frequency of T-lymphocyte proliferating in response to mumps, Coxsackie B4 and varicella-zoster antigens was determined. A decreased frequency was found in T lymphocytes able to respond to mumps or Coxsackie B4 when presented together with DR3, as compared with the frequency of T lymphocytes able to respond to these viruses together with other DR determinants. This was not found for varicella-zoster or purified protein derivative of tuberculin. In contrast, an increased frequency was found in T lymphocytes responding to mumps or Coxsackie B4 together with DR4, compared with other DR determinants. The results were similar in Type 1 diabetic and healthy individuals. The results suggest that elements on the DR3 and DR4 molecules may control T-lymphocyte responses to mumps and Coxsackie B4 viruses.
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