Effects of tamoxifen on lipid profile and coagulation parameters in male patients with pubertal gynecomastia.

BACKGROUND/AIM: The estrogenic actions of tamoxifen on lipid profiles and hemostasis have been extensively demonstrated in women. Due to limited experience with this drug in males, it is uncertain whether these effects are also present in men. The aim of our study was to assess the response of blood lipids, lipoproteins, and coagulation parameters in a group of men taking tamoxifen. METHODS: We studied 15 healthy boys with pubertal gynecomastia who were given 10 mg tamoxifen per day. Total testosterone, sex-hormone-binding globulin, estradiol, serum lipids, apolipoprotein B, apolipoprotein A-I, lipoprotein(a), fibrinogen, antithrombin III, von Willebrand factor, and markers of activated coagulation and fibrinolysis were determined at baseline and 1 and 3 months after beginning of the tamoxifen treatment. RESULTS: Total cholesterol and lipoprotein(a) showed moderate but significant decreases from baseline. Low-density lipoprotein and high-density lipoprotein cholesterol concentrations as well as triglyceride and apolipoprotein B levels became lower, but these changes were not statistically significant. Among clotting parameters, antithrombin III was reduced, and von Willebrand factor increased significantly. Markers of activated coagulation and fibrinolysis remained unchanged throughout the period of therapy. CONCLUSIONS: The effects of tamoxifen on blood lipids and hemostasis we found in this group of healthy young men were qualitatively similar, but lesser than those previously described in women.

A novel (288delC) mutation in exon 2 of GPIIb associated with type I Glanzmann's thrombasthenia.

This work reports the molecular genetic analysis of two patients who suffer mucocutaneous haemorrhages, prolonged bleeding time and failure of platelets to aggregate, either spontaneously or in response to agonists. The absence of platelet surface glycoprotein (GP)IIb-IIIa complexes confirmed the clinical diagnosis of Glanzmann's thrombasthenia (GT). Polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis of exon 2 of GPIIb showed polymorphic bands caused by the homozygous deletion of a cytosine at position 288 relative to the translation start site. causing a shifting of the reading frame and appearance of a premature termination codon. The heterozygous relatives showed a reduced platelet content of GPIIb-IIIa, and a correlation was found between the levels of GPIIb mRNA and surface expression of GPIIb-IIIa complexes. Unlike other mRNAs carrying a nonsense mutation, (288Cdel)GPIIb does not force alternative splicing of GPIIb mRNA. As expected, co-transfection of Chinese hamster ovary (CHO) cells with cDNAs encoding GPIIIa and (288delC)GPIIb failed to enhance the surface exposure of GPIIIa. It is concluded that the (288delC)GPIIb mutation is responsible for the thrombasthenic phenotype of the patients. In addition, it has also been determined that heterodimerization of GPIIb-IIIa requires the integrity of exons 2 and 3 of GPIIb.

[Biochemical assessment of nutritional status in the Canary Islands population (1998)]. / Evaluación bioquímica del estado nutricional de la población canaria (1998).

UNLABELLED: Nutrition surveys include information about dietary intake and nutritional status utilising clinical, biochemical and anthropometric measurements. OBJECTIVE: To evaluate the nutritional status of the Canary Island population by means of biochemical and haematological indicators METHODOLOGY: A cross-sectional study was realised in a representative subsample aged 6 to 75 years that participated in the Nutritional Survey of the Canary Islands, 1997-98 (ENCA). We determined levels of ferritin and vitamin B12 (enzyme-immunoassay), serum and erythrocytic folic acid (automated ionic catchment), retinol, tocopherol and carotenes (high performance liquid chromatography) and minerals (atomic absorption spectrometry) RESULTS: There were neither sex, age nor socio-economic differences in the reference population sample and the ENCA sample. The participation rate was 48.8%. 25% of the women had deficit levels of ferritin and the prevalence of anaemia in women over 18 years was 2.9%. 13% of the population had low erythrocyte folic acid levels, that increased with age, and 3.4% had low vitamin B12 levels, which, on the contrary, decreased with age, 15% of the population presented a deficit of alpha-tocopherol and 5.2% of retinol, being more frequent in the youngest group, and 56.4% and 41.1% exhibited low levels of beta-carotene and lycopene respectively. Among mineral and trace elements, low levels of manganese drew attention due to its heightened prevalence, and, to a lesser extent, selenium. CONCLUSIONS: In spite of the complexity of its interpretation, this data yields a precise estimation of nutritional status for certain vitamins and minerals in the Canary Island population.

Use of antithrombin III in critical patients.

OBJECTIVE: To evaluate the effect of the AT III concentrates upon the clinical evolution and hemostatic parameters. DESIGN: Prospective, open, randomized trial. PATIENTS AND PARTICIPANTS: Septic and multiple trauma patients admitted to our Intensive Care Unit. SETTING: Levels of AT III below 70% were used as criteria to choose 36 patients, 20 of whom received treatment with AT III and 16 did not. INTERVENTIONS: AT III concentrates were administered at an initial dose of 60 U/kg followed by 10 U/kg every six hours. RESULTS: The administration of AT III neither contributes to alterations in haemostasis, nor the clinical evolution (evaluated according to Apache II score). CONCLUSIONS: The results suggest that the administration of AT III concentrates to critical patients with acquired low levels, but without manifest DIC, may not be justified; although further studies on a larger population are required to establish definite conclusions.

The heterogeneity of type IIA von Willebrand's disease: studies with protease inhibitors.

The absence of large von Willebrand factor (vWF) multimers from plasma is a characteristic of Type IIA von Willebrand's disease (vWD) and is thought to contribute to the clinical expression of this disorder. Recently, three IIA patients have been reported in whom intermediate and large multimers could be restored if blood were collected in 5 mm EDTA, 6 mmol/L N-ethylmaleimide, and 1 mmol/L leupeptin. This suggested that absence of large multimers resulted from in vitro proteolysis. We have now collected blood from ten Type IIA vWD patients in these inhibitors but were not able to detect large multimers in the plasma of any of them. In addition, intermediate-sized multimers were reduced or completely absent in all. The inclusion of inhibitors in the citrate anticoagulant, as compared to citrate alone, was found to increase the relative proportion of intermediate multimers in some patients but had no effect in others, and in none did it restore large multimers to plasma. The results with platelet vWF were more varied. Four patients showed an absence or decrease of large multimers, whereas in seven patients large multimers were present. When compared with citrate anticoagulant alone, the inclusion of inhibitors in the anticoagulant had little or no effect on the platelet multimeric pattern. 1-Deamino-8-D-Arginine Vasopressin (DDAVP) was administered to six patients from five families. Two patients from one family showed complete correction and a third patient showed almost complete correction of her bleeding time. Two patients showed minimal correction and one showed no detectable correction. An increase in multimer size after DDAVP tended to be associated with correction of the bleeding time. However, in no case did the largest multimers appear in plasma even in patients with complete bleeding time correction. The presence or absence of inhibitors in the anticoagulant had little or no effect on the multimeric pattern after DDAVP. These results indicate that Type IIA vWD is a heterogeneous disorder in which absence of largest and intermediate multimers is an in vivo phenomenon.