Abstract-Factor V (FV) Leiden and thermolabile methylenetetrahydrofolate reductase (MTHFR) are 2 common polymorphisms that have been implicated in vascular thrombosis. We determined whether these mutations predicted an adverse outcome in pregnancy. Second, we looked for an interaction between these 2 mutations in patients with recurrent fetal loss or thrombosis in pregnancy. Primigravid subjects at their booking visit to the National Maternity Hospital (Holles Street, Dublin, Ireland) were screened for the polymorphisms. Thermolabile MTHFR and FV Leiden genotypes were detected by either restriction fragment length polymorphism or heteroduplex capillary chromatography. The carrier frequency of FV Leiden in the screened primigravid population was 2.7% (allele frequency 1.36%), all being heterozygous for the mutation. This value was lower than expected from previous studies in European populations. Forty-nine percent of the screened population (289 of 584) were heterozygous for thermolabile MTHFR, and 10.6% were homozygous (62 of 584). The frequency of the 2 polymorphisms was no higher in those who subsequently developed preeclampsia (nϭ12) or intrauterine growth retardation (nϭ9), and none of the screened population developed thrombosis. However, the frequency of FV Leiden was higher in patients who subsequently miscarried after the first trimester of pregnancy (allele frequency of 5.5%, Pϭ0.0356). Among those positive for FV Leiden, 3 of 27 miscarried, compared with 24 of 572 of FV Leiden-negative patients (11% versus 4.2%). No interaction was found between the 2 mutations in the control or patient populations. In patients with a prior history of venous thrombosis, the carrier rate of FV Leiden was increased (4 of 33, allele frequency of 7.6%, Pϭ0.0115). In contrast, the carrier frequency for thermolabile MTHFR was no higher, and there was no interaction between the 2 mutations. Neither mutation occurred at a significantly higher frequency in patients with a prior history of recurrent fetal loss. In conclusion, FV Leiden is a risk factor for thrombosis in pregnancy and possibly for second-trimester miscarriage independent of thermolabile MTHFR. However, prospective analysis suggests that the risk conferred by FV Leiden is low in a primigravid population. The thermolabile MTHFR genotype was not implicated in any adverse outcome. Key Words: factor V Leiden polymorphism Ⅲ thermolabile methylenetetrahydrofolate reductase polymorphism Ⅲ pregnancy Ⅲ venous thrombosis Ⅲ recurrent fetal loss Ⅲ genetic risk factors

L50H12.5C is an effective antihypertensive regimen in patients with moderate hypertension that is uncontrolled on 50 mg losartan monotherapy, and is the preferred treatment option in these patients compared with increasing the dose of losartan. The additional benefit of losartan on platelet inhibition was not evident in our population at these doses; however, there was evidence to suggest that the uricosuric effects of losartan might ameliorate the uric acid retention effects of therapy with hydrochlorothiazide.

The development of the clinical trial process dates back to the 18th century. More recently, this process has taken on a more disciplined footing, precipitated by the atrocities of World War II and more recently by the thalidomide crises. This article discusses how the informed consent process has evolved alongside the clinical trial process and looks at the new GCP/ICH guidelines, which are now the accepted standard in obtaining consent from participants globally. It also looks at areas of research where obtaining consent and ensuring quality in the process is poorly defined, such as in emergency situations, obtaining consent from children or adolescents, clinical trials in developing countries, and the more recent controversial area of obtaining consent for genetic sampling. © 1997 John Wiley & Sons, Ltd.