Bone mineral density and fracture among prevalent kidney stone cases in the Third National Health and Nutrition Examination Survey.

Concern that people who form kidney stones may have reduced bone mineral density (BMD) and increased fracture risk has motivated clinical and population-based studies, but findings are inconsistent. In this cross-sectional study, we use the Third National Health and Nutrition Examination Survey (NHANES III) to determine whether a history of kidney stones (n = 793) is associated with lower femoral neck BMD and whether the association is similar for men and women. We further ask whether dietary calcium modifies the association between kidney stone history and BMD and whether there is an association between kidney stone history and prevalent spine or wrist fracture. We find that men with kidney stone history have lower femoral neck BMD than men without kidney stone history after adjusting for age, body mass index (BMI), race/ethnicity, and other potential confounders. The effect of kidney stone history on BMD is weaker for women. Men with kidney stone history also are more likely to report prevalent wrist and spine fractures. Dietary calcium, represented by usual milk consumption, is associated positively with BMD for both men and women and modifies the effect of kidney stone history on BMD for men. For men who form kidney stones, milk consumption is associated more strongly with femoral neck BMD than for men without such a history. The effect modification is such that the difference in BMD between men with and without kidney stone history is observed only at lower levels of milk consumption.

A meta-analysis and overview of the literature on treatment options for left-sided ulcerative colitis and ulcerative proctitis.

OBJECTIVES: Therapeutic trials in left-sided ulcerative colitis (L-UC) and ulcerative proctitis (UP) have lacked control for medication type, dose, delivery, and duration of therapy. METHODS: All published therapeutic articles and abstracts in L-UC or UP from 1958-1997 were reviewed. Improvement, remission rates, and adverse events were recorded for all (ALL), placebo-controlled (PC) studies, and for PC studies passing quality assessment (QA) scoring. Meta-analysis was used where appropriate. RESULTS: Left-sided UC: For active disease, 67 studies (17 PC; 10 QA) were identified. Mesalamine enemas achieved remission in a duration but not a dose response (QA), with higher remission rates than steroid enemas (ALL) and clinical improvement rates superior to oral therapies (QA, ALL). Remission maintenance: 17 (six PC, six QA) studies were identified. Mesalamine therapies had comparable remission rates at 6 months, with a possible dose but not delivery effect. Mesalamine enema dosing intervals between QHS to Q3 days maintained efficacy. Reported adverse events were most common with oral sulfasalazine and dose-independent for mesalamine. Withdrawals from therapy were less than placebo, or < or =3%. Ulcerative proctitis: For active disease, 18 (nine PC, three QA) studies were identified. Mesalamine suppositories achieved clinical improvement and remission in a duration but not dose response, with higher rates of remission than topical steroids (ALL). Remission maintenance: three (three PC, two QA) studies were identified. Remission ranged from 75% to 90% (6 months) and 61-90% (12 months) for mesalamine agents. Reported adverse events were most common for mesalamine foam (8%). Withdrawals from therapy were <2%. CONCLUSIONS: In L-UC and UP, the efficacy and side-effect profile of topical mesalamine are dose independent and superior to oral therapies and topical steroids. Economic analysis suggests that use of these agents will also result in an overall decrease in patient costs.

Prospective, randomized, double-blind trial of BQ-123 and bosentan for prevention of vasospasm following subarachnoid hemorrhage in monkeys.

Thirty-one monkeys were randomly divided into three groups to undergo baseline cerebral angiography followed by induction of subarachnoid hemorrhage by placement of autologous blood clot along the right-sided arteries of the anterior circle of Willis (Day 0). The monkeys were then given drug vehicle or one of two endothelin (ET) antagonists, BQ-123 (6 mg/kg/day) or bosentan (5 mg/kg/day) intracisternally. The BQ-123 was administered by continuous infusion from a subcutaneous pump and the bosentan was given by twice-daily injections into an Ommaya reservoir in the subcutaneous space with a catheter along the right middle cerebral artery (MCA). Seven days later (Day 7), angiography was repeated and the animals were killed. Comparison of arterial diameters shown on angiograms between Day 0 and Day 7 groups given placebo and bosentan showed significant reductions in the diameters of the right intradural internal carotid (28% +/- 6% and 30% +/- 6%, respectively, paired t-test, p < 0.05), anterior cerebral artery (29% +/- 8% and 32% +/- 6% respectively +/- 6%, respectively) and MCA (34% +/- 6% and 46% +/- 4%, respectively). Animals injected with BQ-123 had significant narrowing of the right extradural internal carotid artery (7% +/- 6%) and the basilar artery (11% +/- 3%), but not of the right MCA. Comparison of arterial diameters between groups at Day 7 showed significant variance in the right extradural internal carotid, both intradural internal carotid, right middle cerebral, and left anterior cerebral arteries; the animals injected with BQ-123 developed significantly less arterial narrowing these those receiving bosentan and placebo. Bosentan was not detected in the cerebrospinal fluid aspirated from the cisterna magna on Day 7, whereas BQ-123 was detected in two animals. We can infer from these results that BQ-123 prevents vasospasm following subarachnoid hemorrhage in monkeys, that further investigations of ET antagonists are warranted, and that ET may be an important pathophysiological mediator of vasospasm. The lack of efficacy of bosentan may be related to inadequate cerebrospinal fluid levels obtained by administration twice-daily through an Ommaya reservoir.