ABSTRACT
BACKGROUND: Systemic sclerosis (SSc) is a multisystem disease associated with significant morbidity and increased mortality. The prevalence of different gastrointestinal (GI) manifestations has been investigated in multiple, but mainly small, retrospective studies. In this study, we investigated the prevalence and risk for a broad spectrum of GI disorders and malignancies in a large sample of inpatients with SSc in the United States. METHODS: We conducted a retrospective analysis using the 2010-2011 Healthcare Cost and Utilization Project - Nationwide Inpatient Sample (HCUP-NIS). SSc patients were identified by ICD-9-CM code 710.1. Non-SSc patients ("controls") were matched to cases 4:1 by age and sex. We examined demographics, clinical characteristics, and a range of GI conditions. RESULTS: From 15,824,031 total patients, 13,633 cases of SSc were matched to 54,532 controls. The prevalence of GI manifestations among SSc patients was 59.24% compared to 29.96% for controls (P<0.0001). Significantly elevated GI manifestations in SSc patients included dysphagia (4.3% vs. 1.9%, P<0.0001), esophageal reflux (34.8% vs. 15.4%, P<0.0001), Barrett's esophagus (1.7% vs. 0.3%, P<0.0001), constipation (6% vs. 4.6%, P<0.0001), diarrhea (4.5% vs. 2.4%, P<0.0001), fecal incontinence (0.4% vs. 0.2%, P<0.0001), and celiac disease (0.2% vs. 0%, P<0.0001). Some GI disorders were significantly lower in SSc patients, including cholelithiasis (1.6% vs. 2.1%, P<0.0001) and GI malignancies (1% vs. 2.2%, P<0.0001). CONCLUSIONS: Our results emphasize the established association between SSc and esophageal disorders, such as dysphagia and reflux disease. Our analysis indicated a significant positive association between SSc and celiac disease, and a negative association between SSC and cholelithiasis.
ABSTRACT
The goal of the present investigation was to study a full dose-response of quinpirole in production of species-specific 50 kHz ultrasonic vocalizations in rats, and to study involvement of D2 and D3 dopamine receptors in this response. Quinpirole, a D2/D3 dopamine agonist with high selectivity for D2 dopamine receptors, was injected into the shell of the nucleus accumbens. Quinpirole induced species-specific 50 kHz ultrasonic vocalizations at a wide range of doses as compared to saline. The dose-response study showed a triphasic effect of quinpirole and reached two comparable peak responses in the number of emitted vocalizations at 0.25 µg and 6 µg, respectively (a 24-fold dose difference). These two peaks were separated by a decreased phase. A medium dose range (0.5-1.0 µg) of quinpirole consistently depressed production of calls to the control level. Application of antagonists of D2 dopamine receptors (raclopride) and D3 dopamine receptors (U-99194A) before quinpirole revealed that quinpirole activates differentially the D2 and D3 dopamine receptors at different doses. The vocalization response induced by the low dose of quinpirole (0.25 µg) was antagonized by local pretreatment with the D3 receptor antagonist but not by the D2 receptor antagonist. On the other hand, the response induced by the high dose of quinpirole (6 µg) was antagonized by a similar local pretreatment with the D2 receptor antagonist but not by the D3 receptor antagonist. In conclusion, the results indicated that quinpirole can induce 50 kHz vocalizations after its direct intra-accumbens application in rats, and both D2 and D3 dopamine receptors are involved in the response. They play, however, different functional roles, as revealed by the triphasic effect of increasing doses of quinpirole.
