A common prothrombin variant (20210 G to A) increases the risk of myocardial infarction in young women

Using specimens from a population-based case control study among women ages 18 to 44 years in western Washington, we assessed the relationship between carriership of a genetic clotting factor II variant (20210 G-->A) and myocardial infarction (MI). The factor II variant was previously shown to be present in 1% to 2% of the population, to increase the levels of factor II, and to be associated with venous thrombotic disease. Personal interviews and blood samples were obtained from 79 women with a first myocardial infarction and 381 control women identified through random-digit telephone dialing. Polymerase chain reaction (PCR) method was used to determine the factor II genotypes. The factor II 20210 G to A transition was present more often in women with MI (5.1%) than among control women (1.6%). The age-adjusted odds ratio for MI was 4.0 (95% confidence interval 1.1 to 15.1). The relative risk was high when another major cardiovascular risk factor was also present, such as smoking (odds ratio 43.3, 95% confidence interval 6.7 to 281), and the risk seemed limited to those with other risk factors. These results, in which the effect of major coronary risk factors is enhanced fourfold to sixfold by the prothrombin variant, are similar to those previously reported for another genetic clotting abnormality, factor V Leiden. We conclude that factor II 20210 G to A increases the risk of myocardial infarction in young women, especially in the women with other major risk factors for coronary heart disease.     

Laparoscopic Nissen fundoplication for the treatment of gastroesophageal reflux disease

The Nissen fundoplication is the most common operative approach to the correction of gastroesophageal reflux disease (GERD) in the United States. This report describes our success in performing this anti-reflux procedure laparoscopically in 28 patients with symptomatic GERD refractory to conventional medical therapy. Our laparoscopic technique does not differ significantly from the traditional, open Nissen fundoplication. After surgery, all patients reported symptomatic relief, and none required medication for the control of reflux symptoms. Oral feedings were begun on the first postoperative day, and patients were typically discharged on the second day after surgery. All but two patients resumed normal eating within an average of 26 days. Two patients experienced longer term postoperative dysphagia, including one who had undergone a highly selective vagotomy concurrent with the antireflux surgery.     

Excess corticotropin releasing hormone-binding protein in the hypothalamic-pituitary-adrenal axis in transgenic mice

Corticotropin-releasing hormone (CRH) is the primary hypothalamic releasing factor that mediates the mammalian stress response. The CRH-binding protein (CRH-BP) is secreted from corticotropes, the pituitary CRH target cells, suggesting that the CRH-BP may modulate hypothalamic-pituitary-adrenal (HPA) axis activity by preventing CRH receptor stimulation. Transgenic mice were generated that constitutively express elevated levels of CRH-BP in the anterior pituitary gland. RNA and protein analyses confirmed the elevation of pituitary CRH-BP. Basal plasma concentrations of corticosterone and adrenocorticotropin hormone (ACTH) are unchanged, and a normal pattern of increased corticosterone and ACTH was observed after restraint stress. However, CRH and vasopressin (AVP) mRNA levels in the transgenic mice are increased by 82 and 35%, respectively, to compensate for the excess CRH-BP, consistent with the idea that CRH-BP levels are important for homeostasis. The transgenic mice exhibit increased activity in standard behavioral tests, and an altered circadian pattern of food intake which may be due to transgene expression in the brain. Alterations in CRH and AVP in response to elevated pituitary CRH-BP clearly demonstrate that regulation of CRH-BP is important in the function of the HPA axis.     

Clinical pharmacokinetics of nifedipine. Implications for the care of the elderly

Nifedipine, the prototype for the dihydropyridine class of calcium antagonists, has been available for 20 years and its efficacy as a vasodilator and an antihypertensive agent is well recognised. The development of the so-called nifedipine gastrointestinal therapeutic system (GITS), which allows once-daily administration, has modified and improved the overall therapeutic profile of nifedipine to such a significant extent that it might almost be considered a new drug entity. The nifedipine GITS is associated with distinct improvements in terms of patient compliance and convenience, and a reduced incidence of adverse effects. With regard to the care of the elderly, this 'new' drug offers the prospect of a well tolerated and effective treatment without major cost implications.