The relationship between esophageal acid exposure and the esophageal response to volumetric distention.

BACKGROUND: Increased esophagogastric junction (EGJ) distensibility is thought to contribute to gastroesophageal reflux disease (GERD). Using the functional lumen imaging probe (FLIP), we aimed to assess the esophageal response to distension among patients undergoing esophageal pH monitoring. METHODS: 25 patients (ages 22-73; 13 females) who underwent ambulatory wireless esophageal pH testing while off proton-pump inhibitors were evaluated with FLIP during sedated upper endoscopy. Esophageal reflux was quantified by total percent acid exposure time (AET; <6% was considered normal). FLIP studies were analyzed using a customized program generate FLIP topography plots to identify esophageal contractility patterns and to calculate the EGJ-distensibility index (DI). Reflux symptoms were assessed with the GERDQ. Values reflect median (interquartile range). RESULTS: Among all patients, the AET was 7.2% (3.7-11.1) and EGJ-DI was 4.2 (2.5-7.6) mm2 /mm Hg. Repetitive antegrade contractions (RACs) were induced in 19/25 (76%) of patients; AET was lower among patients with (6.1%, 3-7.8) than without (14.9, 8.5-22.3) RACs (P = .009). Correlation was weak and insignificant between AET and EGJ-DI, GERDQ and AET, and GERDQ and EGJ-DI. Patients with abnormal AET (n = 16) and normal AET (n = 9) had similar EGJ-DI, 4.6 mm2 /mm Hg (2.9-9.2) vs 3.2 (2.2-5.1), P = .207 and GERDQ, P = .138. CONCLUSIONS: Abnormal esophageal acid exposure was associated with an impaired contractile response to volume distention of the esophagus. This supports that acid exposure is dependent on acid clearance mechanisms.

Indwelling peritoneal catheters in patients with cirrhosis and refractory ascites.

BACKGROUND: The prevalence of spontaneous bacterial peritonitis (SBP) in hospitalised cirrhotics with ascites is 10-30%. Treatment for refractory ascites includes paracenteses, transjugular intrahepatic portosystemic shunt or drain placement; the latter is discouraged due to a perceived infection risk. AIM: This study aimed to evaluate the risk of bacterial peritonitis (BP) with peritoneal drains in patients with Child-Pugh class B or C cirrhosis and determine their impact on survival. METHODS: We conducted a retrospective review of end-stage liver disease (ESLD) patients with non-malignant, refractory ascites who had peritoneal drains placed for ≥3 days at Loyola University between 1999 and 2009. Cell counts were performed at drain placement and within 72 h. BP was defined as ascitic polymorphonuclear neutrophils >250/mm(3) . Univariate analysis assessed the association between demographics, laboratory markers and development of BP. Kaplan-Meier curve estimates by infection were constructed and survival distributions were compared using log-rank statistic. RESULTS: There were 227 drain placements during the study period. Twenty-two per cent were diagnosed with BP (12% had SBP at drain placement; 10% developed BP within 72 h). There was no association between BP and baseline characteristics. Patients who developed BP within 72 h of drain placement had 50% mortality at 5 months compared with 50 months in those without infection (log-rank P ≤ 0.003). CONCLUSION: In ESLD patients who received an indwelling peritoneal catheter, there was 10% risk of developing BP and significant mortality increase. Though placing drains is not the mainstay of treatment for refractory ascites, we confirm the theoretical adverse risk of peritoneal drains on infection and survival in cirrhotics.

Hyperresponsiveness of vitamin D receptor gene expression to 1,25-dihydroxyvitamin D3. A new characteristic of genetic hypercalciuric stone-forming rats.

Hypercalciuria in genetic hypercalciuric stone-forming (GHS) rats is accompanied by intestinal Ca hyperabsorption with normal serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] levels, elevation of intestinal, kidney, and bone vitamin D receptor (VDR) content, and greater 1,25(OH)2D3-induced bone resorption in vitro. To test the hypothesis that hyperresponsiveness of VDR gene expression to 1,25(OH)2D3 may mediate these observations, male GHS and wild-type Sprague- Dawley normocalciuric control rats were fed a normal Ca diet (0.6% Ca) and received a single intraperitoneal injection of either 1,25(OH)2D3 (10-200 ng/100 g body wt) or vehicle. Total RNAs were isolated from both duodenum and kidney cortex, and the VDR and calbindin mRNA levels were determined by Northern blot hybridization using specific cDNA probes. Under basal conditions, VDR mRNA levels in GHS rats were lower in duodenum and higher in kidney compared with wild-type controls. Administration of 1,25(OH)2D3 increased VDR gene expression significantly in GHS but not normocalciuric animals, in a time- and dose-dependent manner. In vivo half-life of VDR mRNA was similar in GHS and control rats in both duodenum and kidney, and was prolonged significantly (from 4-5 to > 8 h) by 1,25(OH)2D3 administration. Neither inhibition of gene transcription by actinomycin D nor inhibition of de novo protein synthesis with cycloheximide blocked the upregulation of VDR gene expression stimulated by 1,25(OH)2D3 administration. No alteration or mutation was detected in the sequence of duodenal VDR mRNA from GHS rats compared with wild-type animals. Furthermore, 1,25(OH)2D3 administration also led to an increase in duodenal and renal calbindin mRNA levels in GHS rats, whereas they were either suppressed or unchanged in wild-type animals. The results suggest that GHS rats hyperrespond to minimal doses of 1,25(OH)2D3 by an upregulation of VDR gene expression. This hyperresponsiveness of GHS rats to 1,25(OH)2D3 (a) occurs through an increase in VDR mRNA stability without involving alteration in gene transcription, de novo protein synthesis, or mRNA sequence; and (b) is likely of functional significance, and affects VDR-responsive genes in 1, 25(OH)2D3 target tissues. This unique characteristic suggests that GHS rats may be susceptible to minimal fluctuations in serum 1, 25(OH)2D3, resulting in increased VDR and VDR-responsive events, which in turn may pathologically amplify the actions of 1,25(OH)2D3 on Ca metabolism that thus contribute to the hypercalciuria and stone formation.