Pregnancy-associated plasma protein A and mortality in haemodialysis.

BACKGROUND: Elevated pregnancy-associated plasma protein A (PAPP-A) levels are associated with increased risk of death in ischaemic heart disease as well as in haemodialysis patients. Previous research indicates that the prognostic value of PAPP-A may be stronger in patients with concomitant diabetes mellitus or signs of inflammation. We studied the association between PAPP-A and outcomes in prevalent haemodialysis patients and hypothesized that diabetes mellitus and inflammation status act as effect modifiers. MATERIALS AND METHODS: Circulating PAPP-A levels were quantified using ELISA. Cox proportional hazards and quantile regression models were used for associations between PAPP-A and mortality. PAPP-A levels were log-transformed for Normality. RESULTS: During 60-month follow-up, 37 (40%) of the 92 participants died. Higher PAPP-A was associated with increased risk of mortality in unadjusted analysis (HR per SD = 1.4, 95% CI = 1-1.9, P = .03) and when adjusted for confounders and cardiovascular risk factors (HR = 1.8, 95% CI = 1.18-2.73, P = .006). An interaction between PAPP-A levels and diabetes mellitus on mortality was found (HR for the multiplicative interaction term = 2.74 95% CI = 1.02-7.37, P = .05). In a quantile regression adjusted for age and sex, one SD increase in PAPP-A was associated with 22 months shorter estimated time until 25% of the patients died (95% CI -35 to -9.1 months). CONCLUSIONS: Increased PAPP-A levels are associated with higher all-cause mortality in prevalent haemodialysis patients with concomitant diabetes mellitus.

Bravo capsule system optimizes intragastric pH monitoring over prolonged time: effects of ghrelin on gastric acid and hormone secretion in the rat.

AIM: To evaluate measurements of intragastric pH with the Bravo capsule system over a prolonged time. METHODS: A Bravo capsule was placed inside the rat gastric body and pH was studied for periods up to five consecutive days. For comparison, a gastric fistula model was used. Effects of ghrelin and esomeprazole, with or without pentagastrin, on gastric pH were studied. In addition, effects of esomeprazole on plasma ghrelin, gastrin and somatostatin were analyzed. RESULTS: All rats recovered after surgery. The average 24-h pH during free feeding was 2.3 +/- 0.1 (n = 20) with a variation of 18% +/- 6% over 5 d. Ghrelin, 2400 pmol/kg, t.i.d. increased pH from 1.7 +/- 0.1 to 3.1 +/- 0.3 (P < 0.01) as recorded with the Bravo system. After esomeprazole (1 mg/kg, 3 mg/kg and 5 mg/kg) there was a dose-dependent pH increase of maximally 3.4 +/- 0.1, with day-to-day variation over the entire period of 8% +/- 3%. The fistula and pH studies generated similar results. Acid inhibition with esomeprazole increased plasma ghrelin from 10 +/- 2 pmol/L to 65 +/- 26 pmol/L (P < 0.001), and somatostatin from 10 +/- 2 pmol/L to 67 +/- 18 pmol/L (P < 0.001). CONCLUSION: pH measurements with the Bravo capsule are reliable, and comparable to those of the gastric fistula model. The Bravo system optimizes accurate intragastric pH monitoring over prolonged periods and allows both short- and long-term evaluation of effects of drugs and hormones.