Serum Unconjugated Bile Acids and Small Bowel Bacterial Overgrowth in Pediatric Intestinal Failure: A Pilot Study

Background: We determined qualitative and quantitative serum unconjugated bile acid (SUBA) levels among children with history of intestinal failure (IF) and suspected small bowel bacterial overgrowth (SBBO). Methods: This was a single‐center, case‐control pilot study conducted at Cincinnati Children's Hospital Medical Center. Children with history of IF and suspected SBBO were enrolled as subjects. Age‐matched children without IF or suspected SBBO served as controls. All participants underwent small bowel fluid sampling for microbial culture analysis. Additionally, serum fractionated and total bile acids were measured by liquid chromatography‐mass spectrometry at enrollment and following treatment for SBBO. Results: SUBA concentrations were elevated in IF subjects (median 1.16 μM, range 0.43–10.65 μM) compared with controls (median 0.10 μM, range 0.05–0.18 μM, P = 0.001). Among SUBA, chenodeoxycholic acid (CDCA) was significantly elevated in subjects (median 0.8 μM, range 0–7.08 μM) compared with controls (median 0 μM, range 0–0.03 μM, P = 0.012). When controls were excluded from analysis, IF subjects with positive aspirates for SBBO demonstrated higher concentration of CDCA (median 7.36 μM, range 1.1–8.28 μM) compared with IF subjects with negative aspirates (median 0.18 μM, range 0–1.06 μM, P = 0.017). Treatment for SBBO did not alter SUBA concentration. Conclusions: SUBA concentrations are elevated in children with history of IF and presumed SBBO compared with non‐IF controls. CDCA was more prevalent in IF subjects with positive aspirates for SBBO compared with IF subjects with negative aspirates. The determination of SUBA concentration may be a useful surrogate to small bowel fluid aspiration in the diagnosis of SBBO in children with history of IF.     

Manifestations of Gastroesophageal Reflux and Response to Omeprazole Therapy in Patients with Chronic Posterior Laryngitis: An Evaluation Based on Clinical Practice

Our aims were to describe clinical characteristics of patients with chronic posterior laryngitis and to predict the response to omeprazole therapy. Ninety-one patients with posterior laryngitis were evaluated by a questionnaire, esophageal manometry and pH recording, and endoscopy. Patients were treated with omeprazole, 20 mg twice daily for 3 months. Therapy was continued another 3 months if necessary. Clinical manifestations of reflux occurred in 84 (92%) patients, abnormal acid reflux in 53 (65%) cases, and esophagitis in 6 of 50 (12%). After 3 months of therapy significant improvement occurred in 30 of 70 patients (41%). Continuing therapy for 3 more months increased the response to 65% (45 of 69 cases). Response to therapy was associated with lower age and lower duration of laryngeal symptoms, but a consistent prediction of the response could not be made. In conclusion, patients with posterior laryngitis frequently present with manifestations of gastroesophageal reflux. Response to therapy can not be predicted with certainty.     

β-amyloid controls altered Reelin expression and processing in Alzheimer's disease

Reelin is a glycoprotein that modulates synaptic function and plasticity in the mature brain, thereby favouring memory formation. We recently reported altered cerebral Reelin expression in Alzheimer's disease (AD). Here we demonstrate pronounced Reelin changes at protein and mRNA levels in the frontal cortex in adult Down's syndrome (DS), where the extra copy of chromosome 21 leads to overexpression of β-amyloid. In cortical extracts of fetal DS samples we detected increased levels of the full-length Reelin and the 310-kDa fragment. Overexpression of mutant human amyloid precursor protein also led to an increase in levels of Reelin fragments in Tg2576 transgenic mice for human β-amyloid. Finally, in vitro Aβ42 treatment of SH-SY5Y neuroblastoma cells led to increased Reelin levels. An altered pattern of Reelin glycosylation was detected in extracts from the frontal cortex of AD patients and in Aβ42-treated SH-SY5Y cells, supporting the notion that β-amyloid triggers altered Reelin processing. These results provide evidence that Reelin expression and processing is altered in several amyloid conditions.     

Z-line examination by the PillCam? SB: Prospective comparison of three ingestion protocols

AIM: To evaluate the Z-line visualization by the PillCam™ SB2 using three different ingestion protocols.METHODS: Ninety consecutive patients undergoing small bowel capsule endoscopy (SBCE) between January and May 2008 were included in the study. They swallowed the capsule in the standing (Group A = 30), supine (Group B = 30) and right supine positions (Group C = 30). Baseline patient characteristics, difficulties in capsule ingestion, esophageal transit times (ETT) and Z-line visualization were noted.RESULTS: No significant differences were found between the groups with regard to baseline patient characteristics, ingestion difficulties and complete SB examinations (P > 0.05). At least 1 frame of the Z-line was detected in 15.8%, 46.7% and 90% of patients in groups A, B and C, respectively (P < 0.001). The average number of Z-line images was 0.21 ± 0.53, 3.23 ± 6.59 and 5.53 ± 7.55 and the mean % of the Z-line detected was 71.3, 25.1 and 8.3, in groups A, B and C, respectively (both P < 0.001). ETT times were longer in the supine group followed by the right supine and the standing groups (median of 237 s vs 64 s and 39 s, respectively; P < 0.001).CONCLUSION: Z-line visualization in patients undergoing SBCE can be accurately achieved in most cases when the capsule is swallowed in the right supine position.     

Z-line examination by the PillCam~(TM) SB:Prospective comparison of three ingestion protocols

AIM:To evaluate the Z-line visualization by the PillCamTM SB2 using three different ingestion protocols. METHODS:Ninety consecutive patients undergoing small bowel capsule endoscopy(SBCE)between January and May 2008 were included in the study. They swallowed the capsule in the standing(Group A= 30),supine(Group B=30)and right supine positions (Group C=30).Baseline patient characteristics, difficulties in capsule ingestion,esophageal transit times(ETT)and Z-line visualization were noted. RESULTS:No significa...     

Ethanol‐Induced Increase of Agouti‐Related Protein (AgRP) Immunoreactivity in the Arcuate Nucleus of the Hypothalamus of C57BL/6J,but not 129/SvJ,Inbred Mice

Background: The melanocortin (MC) system is composed of peptides that are cleaved from the polypeptide precursor, pro‐opiomelanocortin (POMC). Previous research has shown that MC receptor (MCR) agonists reduce, and MCR antagonists increase, ethanol consumption in rats and mice. Consistently, genetic deletion of the endogenous MCR antagonist, agouti‐related protein (AgRP), causes reductions of ethanol‐reinforced lever pressing and binge‐like ethanol drinking in C57BL/6J mice. Ethanol also has direct effects on the central MC system, as chronic exposure to an ethanol‐containing diet causes significant reductions of α‐melanocyte stimulating hormone (α‐MSH) immunoreactivity in specific brain regions of Sprague‐Dawley rats. Together, these observations suggest that the central MC system modulates neurobiological responses to ethanol. To further characterize the role of the MC system in responses to ethanol, here we compared AgRP and α‐MSH immunoreactivity in response to an acute injection of saline or ethanol between high ethanol drinking C57BL/6J mice and moderate ethanol drinking 129/SvJ mice. Methods: Mice received an intraperitoneal (i.p.) injection of ethanol (1.5 g/kg or 3.5 g/kg; mixed in 0.9% saline) or an equivolume of 0.9% saline. Two hours after injection, animals were sacrificed and their brains were processed for AgRP and α‐MSH immunoreactivity. Results: Results indicated that acute ethanol administration triggered a dose‐dependent increase in AgRP immunoreactivity in the arcuate (ARC) of C57BL/6J mice, an effect that was not evident in the 129/SvJ strain. Although acute administration of ethanol did not influence α‐MSH immunoreactivity, C57BL/6J mice had significantly greater overall α‐MSH immunoreactivity in the ARC, dorsomedial, and lateral regions of the hypothalamus relative to the 129/SvJ strain. In contrast, C57BL/6J mice displayed significantly lower α‐MSH immunoreactivity in the medial amygdala. Conclusions: The results show that acute ethanol exposure has direct effects on endogenous AgRP activity in ethanol preferring C57BL/6J mice. It is suggested that ethanol‐induced increases in AgRP may be part of a positive feedback system that stimulates excessive binge‐like ethanol drinking in C57BL/6J mice. Inherent differences in α‐MSH immunoreactivity may contribute to differences in neurobiological responses to ethanol that are characteristically observed between the C57BL/6J and 129/SvJ inbred strains of mice.     

Long-term remission of severe refractory dermatopolymyositis with a weekly-scheme of immunoglobulin followed by rituximab therapy

We report on a 44-year-old woman affected by dermatopolymyositis resistant to conventional therapies who experienced long-term clinical improvement and remission after treatment with intravenous polyvalent immunoglobulin in a weekly schedule followed by rituximab therapy.