Venelin Kounev

Increased rates of drug allergy in inflammatory bowel disease (IBD) patients compared to irritable bowel syndrome (IBS) patients and normal controls

Background and Aims: Drug allergy (rash, angioedema, anaphylactic, anaphylactoid reactions) is a frequently encountered clinical problem, and published reports suggest that it is present in up to 20% of hospitalized patients. The rate of drug allergy among patients with 1BD (Crohns disease (CD), ulcerative colitis (UC)) has not been previously described. We hypothesized that adult patients with chronic gut inflammation would have increased rates of drug allergy compared to controls. Methods: Retrospective observational analysis was performed on all 1BD patients followed at a tertiary referral center. All intake visits were reviewed for histories of drug allergy, defined as emergence of rash, angnoedema, anaphytactic/ anaphylactoid reaction following challenge with the offending agent. Demographic information regarding patients as well as classes of agents inducing allergic reactions were recorded, as was the duration of the IBD. Controls included patients with irritable bowel syndrome as well as healthy volunteers without clinical evidence of gastrointestinal disease. Results: Records of 410 IBD patients (297 CD, 107 UC, 6 indeterminate colitis) were reviewed, as weft as 230 control patients (IBS 50, normal 180). 33.2% of IBD patients and 19% of controls demonstrated drug allergy ( p = < 0.001 Chi-square). There was no difference between the prevalence of drug allergy between CD and UC patients. The duration of disease did not impact on the prevalence of drug allergy. There were significantly more female IBD patients with drug allergy when compared to males (36% vs. 25%; p = < 0 . 0 3 ) which corresponded with an increased rate of drug allergy noted in the female control population. The classes of drugs associated with allergic reactions in IBD patients included penicillin (13.9%), sulfa (8.3%), narcotics (7.1%). The prevalence of antibiotic allergy in the IBD patients was 22% compared with 11% of controls (p = <O.001). Conclusions: The prevalence of drag allergy is significantly higher in patients with IBD compared to patients with IBS or healthy volunteers. Female IBD patients have a higher prevalence of allergic reactions compared to males, but there is no difference in the prevalence of the reactions between UC and CD Drug allergnc IBD patients are a commonly encountered phenotype which pose added clinical challenges in management.

Viral Hepatitis: Hepatitis B (& D)

The field of viral hepatitis including that of hepatitis B is rapidly evolving. There continues to be an explosion of new information not only on treatment options but also on management of those with acute and/or chronic hepatitis B. In light of this, the focus of this chapter is not on addressing information typically in textbooks of hepatology but rather on a framework of specific patient management questions which may be faced by the provider in the care of the patient affected by hepatitis B infection.

Pharmacologic Treatment of Esophageal Dysmotility

Esophageal dysmotility is a medical term that refers to an interruption in the bolus propagation through the esophagus. This chapter provides a description of the esophageal anatomy and physiology, the causes (if known) of esophageal dysmotility, and the current pharmacologic treatments.

Tu1800 Functional Connectivity of Somatosensory Cortex Is Enhanced by Acute Esophageal Acid Exposure in Rats

Earlier studies have shown the effect of acute esophageal acid exposure on cerebral cortical functional connectivity. Effect of chronic acid exposure as well as acute acid challenge in the setting of remote chronic acid exposure is not known. Aim: To determine the effect of chronic esophageal acid exposure with and without acute acid re-challenge on functional connectivity (FC) of anterior cingulate cortex (ACC). Methods: We studied two groups of adult Sprague-Dawley rats (n=11/ per group). One group had esophageal HCl infusion (0.1N, 0.1ml/min) 20 min/day for 7 consecutive days. The other group had normal saline (0.9%) infusion with similar frequency and duration. After a 7-day hiatus, each rat underwent a 6 min scan (effect of chronic remote acid exposure), followed by 10 min HCL infusion (0.1N, 0.2ml/min), followed by a 6 min scan (effect of acid re-challenge). We acquired gradient ECHO images on a 9.4T scanner. All image registrations were performed in FSL/ FLIRT and further processing and analysis was done with AFNI. We used seed-based FC analysis between ACC and the rest of brain (cingulate seeds were chosen based on prior demonstration of positive BOLD activity). FC between ACC and insula was re-studied by seeds placed in the insula based on the positive BOLD signal identified from previous studies. Two-sample independent and paired t-test were applied for between and within group analysis. Multiple comparisons were corrected with Monte-Carlo simulations (p<=0.025, cluster size of 6 voxels).Results: Compared with saline group, chronic acid group exhibited significantly reduced FC (decrease correlation coefficient (CC)) between ACC and middle cingulate (MCC), retrosplenial cortex (RSC), hippocampus, primary and secondary somatosensory (S1 and S2), Caudate Putamen (Cpu) and thalamus in the resting state. Acute acid challenge resulted in increased connectivity (increased CC) between ACC and MCC, RSC, hippocampus, S1, S2, Cpu, thalamus and primary and secondary motor area (M1/M2) in both groups, however, the magnitude of increase was significantly greater for saline compared to acid group. In contrast, the connectivity between ACC and insula significantly decreased after acute acid re-challenge in the chronic acid but not in the saline group (table)(figure) (CC: 0.38 to 0.17,P<0.05). Conclusions: Connectivity of cingulate cortex with a number of brain regions is susceptible to change by chronic and acute acid exposure. Chronic acid exposure reduces cingulate connectivity which can last for at least of 7 days. Acute acid rechallenge in the setting of remote chronic acid exposure affects cingulate connectivity differently from remote chronic acid exposure. In that, it enhances the FC and it affects additional brain regions. Effect of acid re-challenge on ACC-insula FC is opposite to that of other altered connections. Acid-induced Changes in ACC Functional Connectivity with Various Brain Regions (P<0.05)

Tu1104 Objective Identification of Common Daily Activities by Their Manometric Signatures Using Ambulatory Pressure Recording

Background: During pathological assessment of esophageal biopsies several histological features characterizing the diagnosis of microscopic esophagitis [basal cell hyperplasia (BCH), papillary enlongation (PE), dilated intercellular spaces (DIS) and epithelial neutrofilic/eosinophilic infiltration (Neu/Eos)] can be assessed. Limited data are available about the single contribution of these histological abnormalities on the diagnosis of GERD and its related mucosal integrity in well-defined patients with reflux disease. Aim: To determine whether these histological features contribute differently to the diagnosis GERD and to the impairment of mucosal integrity as expressed by baseline impedance (BI) levels. Methods:One hundred and four consecutive patients with typical reflux symptoms underwent upper endoscopy and multiple biopsies were taken at Z-line and 2 cm above it, in order to assess the presence and severity of BCH, PE, DIS and Neu/Eos [0 (absent), 1 (mild), and 2 (marked)]. Within 3 days from endoscopy, patients underwent impedance-pH testing off-therapy. During manual analysis of the impedance-pH tracings, we measured the esophageal acid expsosure time (AET) over the 24 hours and the total (acid + non-acid) number of impedance-detected reflux episodes. We evaluated BI values at 3 and 5cm above the LES, during the overnight rest, for at least 30 minutes after excluding swallows and reflux induced changes. Twenty healthy volunteers (HVs; 11F/9M; mean age 44) who underwent the same procedures were also enrolled as controls. Results:We included 85 patients with an endoscopic/impedancepH diagnosis of GERD (45F/40M; mean age 46) who had esophageal mucosal breaks at upper endoscopy or an abnormal esophageal acid exposure or a normal esophageal acid exposure but a positive reflux-symptom association at impedance-pH testing. Among these patients, BI values at both 3 and 5 cm above the LES positively correlated with the esophageal AET (r2=0.2033, P<0.001 and r2=0.1859, P<0.001, respectively) and the number of impedance-detected reflux episodes (r2=0.1373, P<0.001 and r2=0,1526, P<0.001, respectively). Moreover, as shown in the Table, BCH and DIS were the lesions more significantly correlated with the endoscopic/impedance-pH diagnosis of GERD. No significant correlation was observed between BI values and impedance-pH parameters or histological lesions in HVs (p=ns). Conclusions: BCH and DIS contribute more than PE and Eos/Neu to the endoscopic/ impedance-pH diagnosis of GERD. Moreover, the same lesions seem to play a greater role than PE and Eos/Neu in determining mucosal integrity impairment as expressed by BI values in GERD patients. Overall, BCH and DIS can be considered the histological markers requiring more carefully evaluation during pathologic assessment in order to help the diagnosis of GERD. Correlation of BI levels with ME histologic features

Su1972 Characterization of a Rodent Model for Functional MRI Studies of Esophageal Acid Related Sensory Physiology

Background: Insula represents an important site in the brain for multi-modal convergence and has been implicated in processing of visceral sensation. Earlier fMRI studies in humans (Lawall, et al. Am J Physiol 2008;294:G787-94) have shown activation and sensitization of insula in response to esophageal acid stimulation. However, response characteristics of insular neurons to esophageal chemical and mechanical stimulation have not been studied. Aims: Our aims in this study were: (i) to determine the influence of esophageal acid stimulation on the insular cortex neurons (ICNs) and (ii) to characterize the responses of these neurons to esophageal distension (ED) and colorectal distension (CRD) before and after esophageal acid exposure. Methods: Eleven male rats (SD, 300-400g) were initially anaesthetized with a mixture of α-chloralose (80mg/kg, i.p.) + urethane (800mg/kg, i.p.). The anesthetics were periodically supplemented (i.v.) every 3 hours with one-fourth of the initial dose and the blood pressure was constantly monitored. A craniotomy (Bregma: +2.5 to -2.5 mm, 2.0 to 7.0 mm lateral) was performed to access insular cortex (IC). Extracellular recordings from the ICNs (Bregma: +1.8 to -2.2 mm, 5.0 to 7.4 mm lateral, 5.8 to 7.8 mm dorso-ventral) were made from the neurons that responded to ED (30-60 mmHg) and/or CRD (30-60 mmHg). After characterization of ICNs to visceral stimulation (ED and CRD), 0.1 ml of PBS (0.1M, pH 7.4) was infused slowly (0.1ml/min) into the esophagus followed by the same volume of 0.1N HCl (pH 1.2). The infusate (0.1 ml) was applied three times at 60s, 300s and 540s. The interval of each infusion time was 4 minutes. The ED and CRD were repeated 15 minutes after acid infusion to study the responses of neurons. Results: Fifteen ED or CRD sensitive neurons were studied for their responses to PBS and acid infusion. All neurons (15/15, 100%) exhibited excitation (p<0.05) following acid infusion, whereas PBS had no effect on the responses of these neurons. Eleven EDand 10 CRDresponsive neurons were fully characterized to preand post-acid condition. Following acid infusion, 11/11 (100%) ED-responsive neurons exhibited increased activity in response to ED. In contrast, 10/10 (100%) CRD-responsive neurons exhibited decreased activity during CRD. In addition, acid, but not PBS, infusion increased the spontaneous firing of all recorded neurons and continued for 30 to 45 minutes after cessation of infusion. Conclusions: Intraesophageal acid infusion significantly alters the response characteristics of ICNs in rats. Esophageal acid infusion differentially modulates the activities of ICNs that receive convergent input from esophagus and colon.