Predictors of adequate ultrasound quality for hepatocellular carcinoma surveillance in patients with cirrhosis.

BACKGROUND: Abdominal ultrasound fails to detect over one-fourth of hepatocellular carcinoma (HCC) at an early stage in patients with cirrhosis. Identifying patients in whom ultrasound is of inadequate quality can inform interventions to improve surveillance effectiveness. AIM: To evaluate and identify predictors of ultrasound quality in patients with cirrhosis. METHODS: We performed a retrospective cohort study among patients who underwent ultrasound examination for a cirrhosis-related indication between April 2015 and October 2015. Three fellowship-trained abdominal radiologists collectively reviewed all ultrasound exams and categorised exam quality as definitely adequate, likely adequate, likely inadequate and definitely inadequate to exclude liver lesions. We performed multivariable logistic regression to determine characteristics associated with inadequate ultrasound quality. RESULTS: Among 941 patients, 191 (20.3%) ultrasounds were inadequate for excluding HCC- 134 definitely inadequate and 57 likely inadequate. In multivariable analysis, inadequate quality was associated with male gender (OR 1.68, 95% CI 1.14-2.48), body mass index category (OR 1.67, 95% CI 1.45-1.93), Child-Pugh B or C cirrhosis (OR 1.93, 95% CI 1.32-2.81), alcohol-related cirrhosis (OR 2.11, 95% CI 1.33-3.37), NASH cirrhosis (OR 2.87, 95% CI 1.71-4.80), and in-patient status (OR 1.55, 95% CI 1.01-2.37). Ultrasounds were inadequate in over one-third of patients with Child-Pugh C cirrhosis, BMI >35, or NASH cirrhosis. CONCLUSIONS: One in five ultrasounds in patients with cirrhosis are inadequate for exclusion of HCC, which can contribute to surveillance failure. Alternative surveillance modalities are needed in subgroups prone to inadequate ultrasounds including obese patients, those with Child Pugh B or C cirrhosis, and those with alcohol- or NASH-related cirrhosis.

[The impact of neurological and medical complications on the mortality and functional situation of acute stroke patients]. / Impacto de las complicaciones neurologicas y medicas sobre la mortalidad y situacion funcional de pacientes con ictus agudo.

INTRODUCTION: Stroke patients have a high risk of presenting complications, the appearance of which can condition the prognosis of the stroke. We studied the frequency and impact of the onset of several different complications on the early and mid-term prognosis of these patients. PATIENTS AND METHODS: We conducted an observation-based study of the patients admitted to a stroke unit. The complications that occurred while hospitalised were recorded, a distinction being drawn between neurological and medical complications. The study examined their influence, according to the subtype of stroke, on intra-hospital mortality and that at 90 days, as well as on the functional situation at 90 days, by analysing the clinical factors that are predictive for the appearance of complications. RESULTS: The sample consisted of 847 patients. Altogether, 29.5% of the patients presented complications, which were more frequent in haemorrhagic stroke (50.5% versus 26.6%; p < 0.0001). The most usual complications were of a neurological nature (21%). For both subtypes, the presence of complications was associated with a higher rate of mortality both in hospital (2.1% versus 12.6%; p < 0.0001) and at 90 days (5.7% versus 29.6%; p < 0.0001), and a lower probability of independence at 90 days (72.9% versus 30.4%; p < 0.0001). The severity of the stroke on admission revealed itself as the most powerful predictor of the onset of any type of complication. CONCLUSIONS: The appearance of complications during the acute phase of the stroke has an adverse influence on mortality and on the functional prognosis. The identification of predictive factors could reduce the impact upon the progress of acute stroke patients.

TITLE: Impacto de las complicaciones neurologicas y medicas sobre la mortalidad y situacion funcional de pacientes con ictus agudo.Introduccion. Los pacientes con ictus presentan un elevado riesgo de presentar complicaciones. Su aparicion puede condicionar el pronostico del ictus. Estudiamos la frecuencia y el impacto de la aparicion de diversas complicaciones en el pronostico precoz y a medio plazo en estos pacientes. Pacientes y metodos. Estudio observacional de los pacientes ingresados en una unidad de ictus. Se registraron las complicaciones durante su estancia, distinguiendose entre complicaciones neurologicas y medicas. Se estudio la influencia de estas segun subtipo de ictus en la mortalidad intrahospitalaria y a los 90 dias, y en la situacion funcional a los 90 dias, analizandose los factores clinicos predictores para la aparicion de complicaciones. Resultados. Muestra de 847 pacientes. Un 29,5% de los pacientes presento complicaciones, que fueron mas frecuentes en el ictus hemorragico (50,5% frente a 26,6%; p < 0,0001). Las complicaciones mas habituales fueron las neurologicas (21%). Para ambos subtipos, la presencia de complicaciones se asocio a mayor mortalidad intrahospitalaria (2,1% frente a 12,6%; p < 0,0001) y a 90 dias (5,7% frente a 29,6%; p < 0,0001), y menor probabilidad de independencia a 90 dias (72,9% frente a 30,4%; p < 0,0001). La gravedad del ictus al ingreso se mostro como el predictor mas potente en la aparicion de cualquier tipo de complicacion. Conclusiones. La aparicion de complicaciones durante la fase aguda del ictus influye de forma adversa en la mortalidad y en el pronostico funcional. La identificacion de factores predictores podria disminuir el impacto sobre la evolucion del paciente con un ictus agudo.

Functional outcome of stroke and the cumulative experience of a stroke unit.

OBJECTIVE: Patients with acute stroke are more likely to survive and achieve independence if they are treated in a stroke unit. Available information in our setting is scarce. We analyse the outcomes of our patients on the basis of cumulative experience in a stroke unit. PATIENTS AND METHODS: A retrospective cohort study of patients admitted to a stroke unit. We differentiate between two groups according to the year of admission: group A (July 2007-December 2009) and group B (January 2010-December 2011), analysing early outcome based on the score on the National Institute of Health stroke scale and mortality at discharge, and medium-term outcome in terms of mortality and functional status according to the modified Rankin scale at three months. RESULTS: A total 1070 patients were included. There were no differences between groups with respect to favourable outcome (68.3% vs 63.9), hospital mortality (5.1% vs 6.6%), or 90-day mortality (12.8% vs 13.1%). The percentage of patients who were independent at 90 days was greater in group B (56.3% vs 65.5%, P=.03). In the multivariate analysis adjusted for stroke subtype and fibrinolytic therapy, the association between patient independence and admission period remained present. CONCLUSIONS: The probability of functional independence in our patients increased alongside accumulated experience in our stroke unit with no differences in mortality.

Clinical and neuroradiological signs in adults with type 1 neurofibromatosis.

INTRODUCTION: Type 1 neurofibromatosis is the most common neurocutaneous syndrome. Most published case series study the paediatric population. MATERIAL AND METHODS: Cross-sectional study of cases of type 1 neurofibromatosis from neurology departments that were recorded in a database. We analysed the different clinical variables providing the diagnosis as well as demographic and neuroradiological variables. RESULTS: We found a total of 31 patients with type 1 neurofibromatosis. The mean age was 28.9 years and 58.4% were women. Subjects with unidentified bright objects (UBOs) were younger than those without them (22.45±8.22 years vs. 32.5±10.64; P=.011). In contrast, subjects with neurofibromas were older than those without them (30.56±10.68 years vs. 18.25±4.34; P=.032). No sex differences were found in the presentation of clinical or radiological variables. Seven patients (22.6%) had tumours; 3 were optic pathway gliomas (1 bilateral), 3 were plexiform neurofibromas, and 1 was a pilocytic astrocytoma in the brainstem. CONCLUSIONS: Patients with type 1 neurofibromatosis presented both peripheral neurofibromas and tumorous lesions of the central nervous system. Subjects with neurofibromas were older than those who did not present them, while subjects with UBOs were younger than those without such lesions.

First interim analysis of the GIDEON (Global Investigation of therapeutic decisions in hepatocellular carcinoma and of its treatment with sorafeNib) non-interventional study.

AIMS: Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib (GIDEON), a global, non-interventional, surveillance study, aims to evaluate the safety of sorafenib in all patients with unresectable hepatocellular carcinoma (uHCC) under real-life practice conditions, particularly Child-Pugh B patients, who were not well represented in clinical trials. METHODS: Treatment decisions are determined by each physician according to local prescribing guidelines and clinical practice. Patients with uHCC who are candidates for systemic therapy, and for whom a decision has been made to treat with sorafenib, are eligible for inclusion. Demographic data and medical and disease history are recorded at entry. Sorafenib dosing and adverse events (AEs) are collected throughout the study. RESULTS: From January 2009 to April 2011, >3000 patients from 39 countries were enrolled. The prespecified first interim analysis was conducted when the initial approximately 500 treated patients had been followed up for ≥4 months; 479 were valid for safety evaluation. Preplanned subgroup analyses indicate differences in patient characteristics, disease aetiology and previous treatments by region. Variation in sorafenib dosing by specialty are also observed; Child-Pugh status did not appear to influence the starting dose of sorafenib. The type and incidence of AEs was consistent with findings from previous clinical studies. AE profiles were comparable between Child-Pugh subgroups. DISCUSSION: The GIDEON study is generating a large, robust database from a broad population of patients with uHCC. First interim analyses have shown global and regional differences in patient characteristics, disease aetiology and practice patterns. Subsequent planned analyses will allow further evaluation of early trends.

The clinical presentation and prognostic factors for intrahepatic and extrahepatic cholangiocarcinoma in a tertiary care centre.

BACKGROUND: The incidence of cholangiocarcinoma is rising. Accurate predictors of survival at diagnosis are not well defined. AIM: To clarify the clinical presentation and prognostic factors of intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma in a contemporary cohort of patients. METHODS: Records for consecutive patients at the University of Michigan hospital diagnosed with cholangiocarcinoma between January 2003 and April 2008 were reviewed. RESULTS: In all, 136 patients had cholangiocarcinoma (79 intra- and 57 extrahepatic cholangiocarcinoma). Median survival was 27.3 months-25.8 months for intrahepatic cholangiocarcinoma and 30.3 months for extrahepatic cholangiocarcinoma. Independent predictors of mortality at presentation on multivariate analysis were elevated bilirubin level (HR 1.04, 95%CI 1.01-1.07), CA 19-9 levels >100 U/mL (HR 1.90, 95%CI 1.17-3.08) and stage of disease (HR 1.51, 95%CI 1.16-1.96). After adjusting for baseline prognostic factors, surgical therapy was associated with improved survival (HR 0.48; 95% CI 0.26-0.88). There were no significant differences regarding clinical presentation, disease stage (P = 0.98), and survival (P = 0.51) between intra- and extrahepatic cholangiocarcinoma. CONCLUSIONS: Survival for cholangiocarcinoma remains poor with no significant difference in outcomes between intra- and extrahepatic cholangiocarcinoma. Stage of disease, bilirubin level and CA 19-9 level are important prognostic factors at presentation. Surgical therapy provides similar efficacy for both tumours when adjusted for other prognostic variables.

Geographic variation in organ availability is responsible for disparities in liver transplantation between Hispanics and Caucasians.

The aims of this study were to determine whether disparities in waiting list outcomes exist for Hispanics and African Americans during the post-MELD era, and to investigate interactions between disparities and geography. Scientific Registry of Transplant Recipients data were used to compare Hispanics and African Americans to Caucasians listed between 2003 and 2008. Endpoints included (i) receipt of a liver transplant and (ii) death or removal from the waiting list for being too sick or medically unsuitable. Adjustment for possible confounders was performed using multivariate Cox regression, with adjustment for geographic variation using a fixed-effects multilevel model. In multivariate analysis, African Americans have similar hazard of transplantation and death/removal as Caucasians during the post-MELD era. However, Hispanics are less likely to receive a transplant than Caucasians despite adjustment for potential confounders (HR 0.80, 95% CI 0.77-0.83), while having a similar hazard of death/removal. This effect disappeared after adjusting for unequal regional distribution of Hispanics, who represent 8% of patients in donation service areas (DSAs) having median waiting times of < or = 155 days versus 19% in DSAs with median waiting times of >155 days. In conclusion, disparities in liver transplantation exist for Hispanics during the post-MELD era, caused by geographic variation in organ availability.

Meta-analysis: surveillance with ultrasound for early-stage hepatocellular carcinoma in patients with cirrhosis.

BACKGROUND: A majority of studies investigating the accuracy of ultrasound for detecting hepatocellular carcinoma (HCC) do not reflect how this test is used for surveillance vs. diagnosis. AIM: To determine the performance characteristics of surveillance with ultrasound for the detection of HCC, particularly early HCC as defined by the Milan criteria. METHODS: A systematic literature review using the MEDLINE and SCOPUS databases yielded six studies that evaluated the accuracy of ultrasound for HCC at any stage and 13 studies that were specific to early HCC. RESULTS: Surveillance ultrasound detected the majority of tumours before they presented clinically, with a pooled sensitivity of 94%. However, ultrasound was less effective for detecting early HCC with a sensitivity of 63%. Alpha-fetoprotein provided no additional benefit to ultrasound. Meta-regression analysis demonstrated a significantly higher sensitivity for early HCC with ultrasound every 6 months than with annual surveillance. Current studies have limitations such as verification bias and are of suboptimal quality. CONCLUSIONS: Surveillance with ultrasound demonstrates limited sensitivity for early HCC, although this may be improved by testing at 6-month intervals. Currently available evidence evaluating surveillance ultrasound has significant limitations and future studies are necessary to determine optimal surveillance methods for early HCC.

A novel model measuring the harm of transplanting hepatocellular carcinoma exceeding Milan criteria.

No empirical studies have defined the posttransplant survival that would justify expansion of the Milan criteria for liver transplantation of hepatocellular carcinoma. We created a Markov model comparing the survival benefit of transplantation for a patient with >Milan HCC, versus the harm caused to other patients on the waiting list. In the base-case analysis, the strategy of transplanting the patient with >Milan HCC resulted in a 44% increased risk of death and a utility loss of 3 quality-adjusted years of life across the pre- and posttransplant periods for a nationally representative cohort of patients on the waiting list. This harm outweighed the benefit of transplantation for a patient with >Milan HCC having a 5-year posttransplant survival of less than 61%. This survival threshold was most sensitive to geographic variations in organ shortage, with the threshold varying from 25% (Region 3) to >72% (Regions 1, 5, 7 and 9). In conclusion, expansion of the Milan criteria will require demonstrating high survival rates for the newly eligible patients-approximately 61% at 5 years after transplantation. In regions with less severe organ shortage, a more aggressive approach to transplanting these patients may be justified.

Advances in critical care hepatology.

Complications of liver disease are commonly seen in the intensive care unit (ICU). When evaluating patients with liver disease in the ICU, it is important to determine whether it is acute or chronic liver disease. Because the pathophysiological mechanisms differ among acute and chronic liver, they will be consider separately in this review. Significant advances in the management of acute liver failure highlight the importance of intracranial pressure monitoring for Grade III/IV encephalopathy, and suggest that moderate hypothermia may be a promising treatment for these patients with refractory intracranial hypertension. Chronic liver disease is best discussed in terms of the various complications that may ensue such as ascites, hepatorenal syndrome, spontaneous bacterial peritonitis, variceal hemorrhage and hepatic encephalopathy. Each of these conditions will be discussed with specific attention to critical care management.

Relationship between diabetes mellitus and adenocarcinoma of the oesophagus and gastric cardia.

BACKGROUND: Obesity is a risk factor for adenocarcinomas of the oesophagus and gastric cardia. Diabetes mellitus might mediate that association. AIM: To estimate the risk of diabetes mellitus on the development of adenocarcinoma of distal oesophagus and gastric cardia beyond that of gastro-oesophageal reflux disease. METHODS: A case-control study was performed using a national administrative database of the Veterans Administration. RESULTS: A total of 311 cases of cancer and 10,154 controls were identified. Gender, age, and race were risks for cancer. Diabetes was diagnosed in 36% of cases, and 32% of controls (P = 0.15). Diabetic complications were diagnosed in 14% of cases and 13% of controls (P = 0.60). Multiple logistic regression confirmed the absence of an association between cancer and diabetes (odds ratio 1.1, 95% confidence interval 0.8-1.5) or diabetic complications (odds ratio 0.8, 95% confidence interval 0.6-1.3), adjusting for age, gender, and race. CONCLUSIONS: Within the limitations of this case-control study, there is no evidence of an association between diabetes and adenocarcinoma of the oesophagus or gastric cardia among US veterans with gastro-oesophageal reflux disease.

Modification of mediators of immune reaction after general anaesthesia.

UNLABELLED: The adverse reactions that may occur during a surgical intervention are of concern to anesthesiologists and allergists due to the civil responsibility they entail and the increased demand for healthcare in allergology units. The aim of the present study was to determine the prevalence of adverse reactions in our setting (Island of Lanzarote) and modifications to immune response mediators using three types of representative myorelaxants (succinylcholine, cisatracurium and vecuronium) in order to predict and prevent adverse reactions. MATERIAL AND METHODS: We performed a prospective, cross sectional, observational study in a population of 201 patients scheduled to undergo surgery in the Surgery Department of the Lanzarote General Hospital from October 1998. Three groups were retrospectively selected: vecuronium (73 patients), cisatracurium (80 patients), and succinylcholine (48 patients). Blood was extracted from all patients before and after the intervention and the following in vitro variables were evaluated: histaminemia, eosinophil cationic protein, tryptase, IgE to latex, CD4/CD8 fractions, total lymphocytes, total IgE, C3 and C4, and also the histaminuria. CONCLUSIONS: The mean age of the patients was 41 years with a predominance of women. Sixty percent had not previously undergone surgery. The mean operating time was 2 hours. Digestive surgery accounted for the greatest number of interventions (38.8 %) and most of the patients had no personal history of atopy (91.5 %). The greatest number of perioperative reactions was produced by cisatracurium (38.8 %), followed by succinylcholine (27.4 %) and vecuronium (20 %). The reactions observed were immediate type 1 and 2 reactions. All reactions were reversible without sequelae. Histaminuria levels were significantly decreased in the cisatracurium group. Histaminemia and eosinophil cationic protein showed no significant changes in any of the three groups. Tryptase concentrations in blood did not increase in the postoperative period in any of the three groups. On the contrary, concentrations were significantly lower than basal values. In the vecuronium and succinylcholine groups, CD4/CD8 fractions decreased in the postoperative period. Total lymphocytes decreased in all three groups. Total IgE tended to decrease in the cisatracurium and succinylcholine groups. IgE to latex was negative in the three groups. Specific IgE to succinylcholine was unmodified. C3 complement fraction was unmodified in all three groups and C4 fraction was reduced in the vecuronium group. In our setting and in our patients, the three myorelaxants produced immunosuppression of immune response mediators. The present study confirms that tests for allergy to myorelaxants are not indicated in the preoperative period.

Hepatocellular carcinoma.

The number of papers published regarding hepatocellular carcinoma between 1999 and 2001 increased from previous years. This year a study confirmed the increase in incidence in the United States. Also, several studies established for the first time that tobacco smoking was a risk factor for the development of this tumor. Several studies established that the process of angiogenesis is critical for the development of hepatocellular carcinoma, and one paper indicated that inhibiting this process might lead to possible treatment of this tumor. Resection was compared with liver transplantation for the first time in two studies. It was shown that transplantation offered the overall best long-term option, but in a certain group of patients without portal hypertension and well-preserved liver function resection is the best option.

Dextran sulfate sodium-induced murine colitis activates NF-kappaB and increases galanin-1 receptor expression.

Galanin is widely distributed in enteric nerve terminals and acts to modulate intestinal motility by altering smooth muscle contraction. This ligand causes Cl(-) secretion when colonic epithelial cells express the galanin-1 receptor (Gal1-R) subtype. Because Gal1-R expression by colonic epithelia is upregulated by the transcription factor nuclear factor-kappaB (NF-kappaB), increasingly appreciated as critical in the pathophysiology of inflammatory bowel disease, we wondered whether the diarrhea associated with this condition could be due to NF-kappaB-mediated increases in Gal1-R expression. To test this hypothesis, we provided oral dextran sulfate sodium (DSS) to C57BL/6J mice. Although Gal1-R are not normally expressed by epithelial cells lining the mouse colon, DSS treatment resulted in increased NF-kappaB activation and Gal1-R expression. Whereas galanin had no effect on murine colonic tissues studied ex vivo, it progressively increased short-circuit current and colonic fluid secretion in DSS-treated mice. Concomitant parenteral administration of the NF-kappaB inhibitor dexamethasone attenuated the activation of this transcription factor by DSS, inhibiting the increase in Gal1-R expression. Although Gal1-R-specific antagonists do not exist, intracolonic administration of commercially available galanin antibody diminished the DSS-induced increase in colonic fluid accumulation. Overall, these data demonstrate that a significant component of the excessive fluid secretion observed in DSS-treated mice is due to increased Gal1-R expression.

Endoscopic transpapillary drainage of pancreatic abscess: technique and results.

BACKGROUND: Pancreatic abscess is one of the serious complications of acute pancreatitis. Traditionally, pancreatic abscess has been treated by operative drainage. Based on experience with endoscopic transpapillary drainage of pseudocysts, a similar technique was used in patients with pancreatic abscess. METHOD: Patients were evaluated by endoscopic retrograde cholangiopancreatography. In those with pancreatic abscess communicating with the main pancreatic duct, pancreatic sphincterotomy, saline irrigation of the abscess cavity, and catheter dilation followed by 10F pancreatic stent placement were done. Instillation of gentamicin and nasopancreatic catheter drainage were used in difficult cases. RESULTS: Of 22 patients with pancreatic abscess, 11 underwent endoscopic transpapillary drainage with technical success in 10 patients (90%); 8 patients (74%) had resolution of pancreatic abscess, clinically and radiographically. Intracavitary instillation of gentamicin and nasopancreatic catheter drainage were used in 2 patients. Two patients in whom endoscopic transpapillary drainage failed underwent operative drainage with a favorable outcome, and the one patient in whom endoscopic treatment was technically unsuccessful underwent successful percutaneous drainage. One patient had mild pancreatitis. CONCLUSION: Endoscopic transpapillary drainage is an effective nonoperative therapy for selected cases of pancreatic abscess and is associated with minimal morbidity and no mortality.

Azoxymethane-induced fulminant hepatic failure in C57BL/6J mice: characterization of a new animal model.

Without transplantation, approximately 50-90% of all patients with fulminant hepatic failure (FHF) die. This poor outcome is due in part to the absence of an appropriate animal model, which would allow for a greater understanding of the pathophysiology of this syndrome. Given the reports of liver injury in humans and livestock fed cycad palm nuts on the island of Guam, we hypothesized that the active ingredient azoxymethane (AOM) could cause FHF. We therefore evaluated AOM in C57BL/6J mice. Histologically, we observed microvesicular steatosis 2 h, sinusoidal dilatation 4 h, and centrilobular necrosis 20 h after AOM administration, and transmission electron microscopy showed that this agent causes mitochondrial injury. FHF was associated with all four stages of encephalopathy, as well as by a prodromal period of decreased eating and drinking lasting approximately 15 h before the development of stage I encephalopathy (i.e., loss of scatter reflex). Late encephalopathy was associated with increased arterial ammonia, decreased serum glucose, and evidence of brain edema (astrocyte swelling). We show that AOM-induced FHF is highly reproducible, without evidence of lot-to-lot variability, and is dose dependent. These findings therefore suggest that AOM is an excellent agent for the study of FHF, as well as indicate that Guamanian FHF may be due to AOM found in unwashed cycad palm nuts.

Pathogenic Escherichia coli increase Cl- secretion from intestinal epithelia by upregulating galanin-1 receptor expression.

Galanin is widely distributed in enteric nerve terminals lining the human gastrointestinal (GI) tract. We have shown previously that galanin-1 receptors (Gal1-R) are expressed by epithelial cells lining the human GI tract, and upon activation cause Cl- secretion. Because expression of this receptor is transcriptionally regulated by nuclear factor-kappa B (NF-kappa B), which is activated by enteric pathogens as a part of the host epithelial response to infection, we investigated whether such bacterial pathogens could directly increase Gal1-R expression in the T84-cell model system. Pathogenic Escherichia coli, but not nonpathogenic E. coli, activate a p50/p65 NF-kappa B complex that binds to oligonucleotides corresponding to a recognition site located within the 5' flanking region of the human GAL1R gene. Pathogenic E. coli, but not normal commensal organisms, increase Gal1-R mRNA synthesis and [(125)I]galanin binding sites. Whereas galanin increases short-circuit current (Isc) approximately 5-fold in uninfected T84 cells, exposure to pathogenic, but not nonpathogenic, E. coli results in galanin increasing Isc approximately 20-fold. To confirm the validity of these in vitro observations, we also studied C57BL/6J mice infected with enterohemorrhagic E. coli (EHEC) by gavage. Infection caused a progressive increase in both NF-kappa B activation and Gal1-R expression, with maximal levels of both observed 3 days after gavage. Ussing chamber studies revealed that colons infected with EHEC, but not those exposed to normal colonic flora, markedly increased Isc in response to galanin. These data indicate that pathogen-induced increases in Gal1-R expression by epithelial cells lining the colon may represent a novel unifying pathway responsible for at least a portion of the excessive fluid secretion observed during infectious diarrhea.