The effects of two phasic oral contraceptives on hemostasis and platelet function.

OBJECTIVE: To compare the effects on hemostatic parameters of a combiphasic oral contraceptive containing desogestrel and ethinyl estradiol (DSG/EE) and a triphasic oral contraceptive containing levonorgestrel and ethinyl estradiol (LNG/EE). METHODS: In an open-label, randomized, group-comparative study in 10 healthy volunteers per treatment group, the effects on parameters of coagulation, anticoagulation, fibrinolysis, antifibrinolysis and platelet function were determined at baseline, after three treatment cycles, and after a post-treatment cycle. Changes from baseline were analyzed using a paired t-test, whereas between-group differences were analyzed by means of an analysis of co-variance. RESULTS: Both OC preparations induced modest changes of some coagulation, anticoagulation, fibrinolysis and antifibrinolysis parameters, although all mean values remained within the normal range. No significant effects were observed with either OC with respect to platelet function. Statistically significant differences between the two preparations could occasionally e observed: the concentrations of antithrombin II (AT-III) and Factor VII were higher with the DSG/EE preparation than with LNG/EE preparation at the end of treatment and AT-III activity, AT-III concentration, Factor X concentration, and plasminogen activity were higher with DSG/EE than with LNG/EE in the post-treatment cycle. CONCLUSIONS: Combiphasic DSG/EE and triphasic LNG/EE, both OCs with a comparable amount of EE per cycle, had no clinically significant effect on the overall hemostatic balance.

[Cardiac function and the skin microcirculation in acromegaly]. / Kardiale Funktion und kutane Mikrozirkulation bei Akromegalie.

The microcirculation was measured by nail-fold capillary video microscopy in 21 patients (12 men, 9 women; mean age 54.7 [29-74] years) with acromegaly. Levels of growth hormone (12.0-71.7 microU/ml) and of somatomedin C (2.4-10.5 IU/ml) were elevated in 10 patients, despite preceding treatment. Eleven patients had an increase in myocardial thickness and nine had impairment of left ventricular function, although only slight in most. Left ventricular hypertrophy was demonstrable even in the absence of hypertension. No patient had evidence of coronary heart disease. Nail-fold capillary video microscopy (capillary density, torque index, reactive hyperaemia, epidermal blood flow) failed to distinguish between successfully treated patients and those with persistently elevated growth hormone concentrations or disease duration of over 5 years. There was no evidence of inadequate capillary blood flow as a cause of abnormal function in hypertrophied organs.

[Cardiac metastasis as cause of therapy-resistant heart failure]. / Herzmetastase als Ursache einer therapierefraktären Herzinsuffizienz.

Ultrasonography revealed a renal tumour (4 x 4 cm) in a 67-year-old man with right-sided lumbar pain and macrohematuria. In addition he had marked nocturnal dyspnoea with dry cough. He had lost about 10 kg in weight. On admission he had atrial fibrillation with an irregular ventricular rate (140 beats/min) and engorgement of the neck veins. Two-dimensional echocardiography, undertaken because of signs of increasing heart failure and a fall of systolic blood pressure to below 100 mm Hg, demonstrated a space-occupying lesion in the right ventricle, 4 x 2 x 1 cm, indicating an intracardiac thrombus or solid tumour. The heart failure continued to worsen, despite treatment with cardiac glycosides, verapamil and diuretics. Hence an exploratory thoracotomy was performed. This revealed an intracardiac tumour which had markedly displaced the right ventricular inflow tract and infiltrated the entire myocardium, but not the tricuspid valve. As much of the tumour as possible was resected, but the patient died postoperatively of heart failure. The intracardiac tumour proved to be a metastasis from the papillary carcinoma of the kidney. This had infiltrated the renal capsule and pelvis and invaded the branches of the right renal vein.

Development of a luminescence immunoassay for follitropin suitable for clinical routine.

We developed a luminescence immunoassay (LIA) for follitropin, based on the synthesis of a follitropin-N-(4-aminobutyl)-N-ethylisoluminol conjugate. The luminescence tracer was purified by gel chromatography. Antibody-bound and non-bound tracer fractions were separated by using a second antibody reagent bound to magnetic particles. The assay can be performed within 24 hours and is sufficiently sensitive for the measurement of all clinically relevant follitropin concentrations including the subnormal range.

[Familial nonneoplastic inappropriate thyrotropin secretion]. / Familiäre, nicht-neoplastische inadäquate Thyreotropin-Inkretion.

A follicular thyroid carcinoma was suspected in a 62-year-old woman after the fifth goitre excision for non-neoplastic inappropriate thyrotropin secretion. Small-follicular adenoma could not be excluded histologically. After an attempt at thyrotropin suppression with L-thyroxine, triiodothyronine, D-thyroxine with L-thyroxine, and bromocriptine had failed, lasting if partial decrease in the maximally elevated TSH levels was achieved with triiodothyroacetic acid (TRIAC). One of the patient's three daughters also has non-neoplastic inappropriate thyrotropin secretion and has had two goitre excisions. It is most likely a familial form of inappropriate TSH secretion.

[Spontaneous thrombocyte aggregation and blood sugar profile in children with diabetes mellitus type I treated with human and porcine insulin]. / Spontane Thrombozytenaggregation und Blutzuckerprofile unter Human- und Schweine-Insulintherapie bei Kindern mit Diabetes mellitus Typ I.

In a three-year bicentric cross-sectional investigation on type I diabetic children aged between 6 and 18 years, blood sugar profiles and spontaneous thrombocyte aggregation were reported besides anamnestic and clinical data. In the children treated with human insulin, raised spontaneous thrombocyte aggregation was significantly more frequent than in those treated with porcine insulin. At the same time, blood sugar fluctuation from day to day measured between 7 and 9 a.m. tended to be raised in the children treated with human insulin; the fluctuation in the diurnal profile measured over 14 days was indeed very much greater. Since the two groups were comparable as to sex distribution, age, duration of disease, quality of compensation, application and dose of insulin, the greater fluctuation of blood sugar in the children treated with human insulin appears to be the cause for the raised spontaneous thrombocyte aggregation.

Microcirculation and hemorheology of children with type I diabetes.

A group of 53 children, suffering from diabetes mellitus type I and a group of 12 healthy children were compared. In both groups the following data were determined: Haemoglobin A1C, retinal blood flow (video fluorescence angiography), erythrocyte velocity in finger nailfold capillaries (video capillaroscopy), capillary tortuosity, plasma viscosity, erythrocyte rigidity, and haematocrit. The degree of capillary tortuosity was significantly elevated and erythrocyte velocity was significantly diminished in the group of diabetic children in comparison to the healthy children. Regarding rheological data there was a significant decrease in erythrocyte deformability for the diabetic children. Diabetic children with good stabilization presented better rheological parameters than the poorly stabilized ones. Although these findings provided sufficient information, it will be necessary to cover a long follow up period to judge the prognosis of good and poorly stabilized diabetic children.

Pharmacodynamics of human insulin (recombinant DNA)--regular, NPH, and mixtures--obtained by the Gerritzen method in healthy volunteers.

The study was concerned with the comparison of the action profile of regular and NPH preparations of human insulin (recombinant DNA) and of PPI (pork purified insulin). In addition, the action profiles of some mixtures (10:90, 15:85, 20:80, 25:75, 30:70) of regular and NPH human insulin were evaluated. The comparisons were based on the Gerritzen test. There was no statistically significant difference in the time-course of the blood glucose levels after administration of NPH human insulin and NPH PPI. A tendency was noted, however, that NPH human insulin has a faster onset of action and that the serum glucose minimum for NPH human insulin lasts longer. The serum glucose curves after the application of regular and NPH human insulin initially lie closer together than after the respective PPI preparations. In the later phase, regular human insulin interferes less with the NPH curves. This means that combinations of regular and NPH human insulin may have a clinically useful action profile. No skin reaction or other adverse reaction was detected after application of human insulin and no antibodies against human insulin and Escherichia coli protein were found.

Comparison of biosynthetic human insulin and pork insulin in the Gerritzen test.

Biosynthetic human insulin (BHI) produced by recombinant DNA technology has been proven to be identical to pancreatic human insulin. It differs from pork insulin in one carboxy-terminal amino acid of the B-chain, where alanine substitutes for threonine. This leads to a higher hydrophilicity and usually lowers the tendency of insulin molecules to aggregate. To study its biologic effect in man, the Gerritzen test was applied. BHI regular (10 IU) or purified pork insulin (PPI) (10 IU) was injected subcutaneously to evaluate the insulin action profile. The time course of plasma glucose levels under both BHI and PPI did not significantly. BHI seems to lower the blood glucose somewhat faster during the first 30 min and, during the late phase, somewhat less than pork insulin. In general, for both BHI and PPI, the onset of action occurs within 15 and 30 min; after 60 min, plasma glucose levels drop by 44.3% for BHI and by 40% for PPI. The plasma glucose minimum was reached about 2 h after injection; therefore, the slope of the plasma glucose fall after 60 min was only marginal. The minimum levels were steady over about 1.75 h. At 2.5 h postinjection plasma glucose rose gradually and reached starting levels after about 7 h. BHI was as well tolerated in the intradermal skin testing as were pork insulin and a placebo solution.

Effects of buformin on the metabolsim of the isolated haemoglobin-free perfused hindlimb of normal rats.

Using the isolated, haemoglobin-free, perfused resting hindlimb of normal rats buformin neither had a direct insulin-like effect on glucose uptake by muscle tissue nor potentiated the effect of insulin on glucose uptake after oral pretreatment for one or several days with low and high doses (30 mg-350 mg/kg). Effects on glycogenolysis could not be detected. Glycerol release was inhibited after several days of pretreatment with low and high doses of buformin. The utilization of added oleate was also partly inhibited. The level of energy rich phosphates in the muscle tissue and oxygen consumption were not affected under any of the conditions used in these experiments.