Abstract-The relationship between salt homeostasis and blood pressure has remained difficult to establish from epidemiological studies of the general population. Recently, mendelian forms of hypertension have demonstrated that mutations that increase renal salt balance lead to higher blood pressure, suggesting that mutations that decrease the net salt balance might have the converse effect. Gitelman's syndrome, caused by loss of function mutations in the Na-Cl cotransporter of the distal convoluted tubule (NCCT), features inherited hypokalemic alkalosis with so-called "normal" blood pressure. We hypothesized that the mild salt wasting of Gitelman's syndrome results in reduced blood pressure and protection from hypertension. We have formally addressed this question through the study of 199 members of a large Amish kindred with Gitelman's syndrome. Through genetic testing, family members were identified as inheriting 0 (nϭ60), 1 (nϭ113), or 2 (nϭ26) mutations in NCCT, permitting an unbiased assessment of the clinical consequences of inheriting these mutations by comparison of the phenotypes of relatives with contrasting genotypes. The results demonstrate high penetrance of hypokalemic alkalosis, hypomagnesemia, and hypocalciuria in patients inheriting 2 mutant NCCT alleles. In addition, the NCCT genotype was a significant predictor of blood pressure, with homozygous mutant family members having significantly lower age-and gender-adjusted systolic and diastolic blood pressures than those of their wild-type relatives. Moreover, both homozygote and heterozygote subjects had significantly higher 24-hour urinary Na ϩ than did wild-type subjects, reflecting a self-selected higher salt intake. Finally, heterozygous children, but not adults, had significantly lower blood pressures than those of the wild-type relatives. These findings provide formal demonstration that inherited mutations that impair renal salt handling lower blood pressure in humans.

No abstract

Since the advent of medical treatments for HIV, the promotion of adherence to these difficult treatment regimens has proven critical to disease management. Three Connecticut state-funded HIV medication adherence programs were evaluated.1 The purpose of this process evaluation was to explore and compare the goals and modality of each adherence program, assess client and staff satisfaction, and provide recommendations for the improvement of these programs. Focus group interviews with clients and individual interviews with staff were conducted at each of the programs. Interviews were transcribed, coded and analyzed with a code and retrieve method of theme identification. Focus group themes included the importance of social support on medication adherence and the "lifesaving" effect the program has had. The staff expressed that although complete adherence should be the long-term objective, more intermediate objectives should be considered (e.g., behavioral changes to increase clients' ability, self-esteem, and self-efficacy to take medications).