No abstract

In patients stabilized on high-dose metformin, the addition of nateglinide improved glycaemic control. The combination of these agents was well tolerated and both doses of nateglinide proved effective. The efficacy of nateglinide 60 mg and the low rate of hypoglycaemia observed at this dose make it suitable for patients close to their therapeutic target on metformin monotherapy.

Fifty patients presenting with acute deep-vein thrombosis were randomized in a prospective, controlled study to determine the safety and efficacy of a treatment with low-molecular-weight (LMW) heparin compared with unfractionated heparin. LMW heparin (n = 24) was administered twice daily subcutaneously at a dose of 2 × 150 anti-Xa units/kg body weight, and unfractionated heparin (n = 26) was given intravenously by continuous infusion at a dose of 450 anti-Xa units/kg body weight daily for 10 days. Doses were adjusted to maintain peak anti-Xa levels between 0.5 and 1.0 anti-Xa units per milliliter. One patient in the unfractionated heparin group and 2 patients in the LMW heparin group suffered from bleeding complications. Two patients on LMW heparin and on unfractionated heparin had high evidence of pulmonary embolism based on defects on ventilation-perfusion scintigraphy. Control phlebography and duplex sonography demonstrated a significant improvement during both treatment regimens. Reperfusion of the deep-vein system was 70% with LMW heparin and 75 % with unfractionated heparin. The anti-Xa levels were significantly higher in the LMW heparin group, and activated partial thromboplastin and thrombin clotting times were significantly higher in the group receiving unfractionated heparin. Thrombin-anti-thrombin III complexes and D-dimer concentration decreased during the treatment, but did not differ between the two regimens. At the end of the treatment period with LMW heparin, protein C and antithrombin III were significantly higher.

Enhanced sialylation of thyrotropin (TSH) prolongs its metabolic clearance rate and thus increases the hormone's in vivo bioactivity. This has been shown for hypothyroid rats and for recombinant human TSH, but there are few data on the sialylation of human serum TSH. The aim of this work was to further study sialylated human serum TSH, its precursors bearing terminal galactose residues, and the role of pharmacological doses of thyrotropinreleasing hormone (TRH) on their secretion under different degrees of primary hypothyroidism.We analyzed serum TSH in patients with subclinical (n=9) and overt primary hypothyroidism (n=13) compared with euthyroid individuals (n=12) and human standard pituitary TSH (IRP 80/558). Blood was drawn before and 30 min after intravenous administration of 200 µg TRH, and TSH was purified by immunoaffinity concentration. The content of sialylated (sialo-) TSH and isoforms bearing terminal galactose (Gal-TSH, asialo-Gal-TSH) was measured by Ricinus communis (RCA 120) affinity chromatography in combination with enzymatic cleavage of sialic acid residues. TSH immunoreactivity was measured by an automated second generation TSH immunoassay.Pituitary TSH contained 16·5 0·8% Gal-TSH. In euthyroid individuals the proportion of Gal-TSH was 14·6 1·9%, whereas TSH in patients with subclinical and overt primary hypothyroidism contained 23·9 3·5% (P<0·05 vs euthyroid individuals) and 21·1 1·7% Gal-TSH respectively. The mean ratio of asialo-Gal TSH was 23·8 0·6% for pituitary TSH, 35·7 4·2% in euthyroid individuals, 48·0 3·3% in patients with subclinical, and 61·5 3·8% (P<0·001 vs euthyroid individuals) in patients with overt primary hypothyroidism. For pituitary TSH the calculated proportion of sialo-TSH was 6·5 0·2%, for euthyroid individuals 20·3 2·8%, for patients with subclinical hypothyroidism 24·1 3·0%, and for patients with overt primary hypothyroidism 40·7 3·0% (P<0·001 vs euthyroid individuals). The proportions of Gal-TSH, asialo-Gal-TSH, and sialo-TSH did not differ significantly before and after TRH administration in the individuals studied.Our data show that patients with subclinical and overt primary hypothyroidism have a markedly increased proportion of serum TSH isoforms bearing terminal galactose and sialic acid residues, which may represent a mechanism for the further stimulation of thyroid function. Pharmacological doses of TRH cause an increased quantity of TSH to be released, but do not significantly alter the proportion of sialylated or terminally galactosylated TSH isoforms.