What is the effect of subepithelial lesions of the esophagus on esophageal motility?

OBJECTIVE: Esophageal motility is regulated both by coordinated stimulation and inhibition of the circular and longitudinal muscle layers of the esophagus. Although there are many diseases known to have an effect on esophageal motility, the effect of subepithelial lesions (SELs) of the esophagus on esophageal motility, which is often detected incidentally, remains still unclear. The aim of this study is to reveal the effect of SELs of the esophagus on esophageal motility evaluating it by high-resolution manometry (HRM). PATIENTS AND METHODS: A total of 32 patients with SELs in the esophagus and 12 healthy individuals were included. All patients and controls included in the study underwent HRM using a Unisensor UniTip High Resolution catheter (Laborie, Amsterdam, Netherlands) and endosonographic examination. RESULTS: The mean age was 52.60±15.56 years (range: 23-79) and the average body mass index (BMI) was 26.63±4.71 kg/m2. Gender, height, weight, and BMI measurements, smoking status, alcohol use, and DM status did not statistically differ significantly between the groups (p>0.05). Of 32 patients with SELs, 65.6% (n=21) had lesions originating in the muscularis propria, while 34.4% had lesions originating in the submucosa. The rate of abnormal motility both in the supine and in upright positions of patients with SELs was found to be significantly higher than in the control group (p=0.001, p<0.01, respectively). In patients with SELs, the incidence of infective motility was higher than the normal group (p=0.001, p<0.01, respectively). As the size of the lesion increases (>2 cm), the probability of abnormal HRM results increased. CONCLUSIONS: SELs of the esophagus have pathological effects on esophageal motility, mainly ineffective esophageal motility disorder.

Is anterior segment OCT superior to slit-lamp biomicroscopic examination for Kayser Flesicher ring in Wilson's disease?

OBJECTIVE: Detection of the Kayser-Fleischer (KF) ring in the diagnostic scoring and treatment follow-up of Wilson's Disease (WD) is important. Slit lamp (SL) biomicroscopic examination has traditionally been used in the evaluation of the KF ring. The role of Anterior Segment Optical Coherence Tomography (AS-OCT), which is used in various corneal diseases, in the detection of KF rings has attracted attention in recent years. In our study, we tried to demonstrate the effectiveness of AS-OCT in detecting the KF ring by comparing it with SL biomicroscopic examination. PATIENTS AND METHODS: 64 of 356 patients followed in our outpatient clinic due to WD were included in the study in the order of their admission to the outpatient clinic. The KF ring was evaluated in both eyes by SL-biomicroscopic examination and AS-OCT. Ophthalmic examination, and findings were performed by the same physician. RESULTS: Age range was 18-67 years, mean 33.06±10.83 years, gender was 39.1% (n: 25) female. At the time of diagnosis, the mean age was 19.48 ± 9.36 years, range was minimum 5 years and maximum 51 years. Clinical presentation was mixed type involvement n: 18 (28.1%), hepatic involvement n: 32 (50%), neurological involvement n: 14 (21.9%). The follow-up period was 2-257 months (74.6±76.16). The presence of KF ring was evaluated together with both AS-OCT and slit-lamp examination, the presence of KF could be detected in both AS-OCT and SL biomicroscopic examination in 10 patients (15.6%), in 12 (18.8%) of the cases KF ring is positive in AS-OCT but was negative in Slit-lamp biomicroscopic examination, in 65.6 (n: 42) of the cases OCT and slit-lamp biomicroscopic examination results were negative. CONCLUSIONS: The sensitivity of AS-OCT in detecting the KF ring was higher than the slit-lamp biomicroscopic examination. AS-OCT can detect early stage of KF rings in Wilson's Disease patients, so that diagnosis and treatment accuracy can be evaluated effectively.

Is belching increasing after bariatric bypass surgery in the long term period?

BACKGROUND AND AIMS: Gastric bypass surgery effectively treats obesity; however, its association with belching, which occurs in other bariatric surgeries, remains unclear. Hence, we aimed to evaluate belching occurrence after gastric bypass surgery. METHODS: We enrolled 12 healthy volunteers and 17 patients (12 and 5 underwent Roux-en-Y gastric bypass and mini-gastric bypass surgeries 24 (18-54) months prior, respectively). Gastrointestinal symptoms were assessed. Gastroscopy was performed, followed by the 24-hour pH-impedance analysis. RESULTS: Age and sex were not statistically different between the two groups (P > 0.05). Patients had a significantly higher mean DeMeester score than the healthy controls (9.11 ± 19.40 vs. 6.04 ± 5.60, P = 0.048), but the pathologic acid reflux (DeMeester score > 14) rate was similar in both groups (11.8% vs. 8.3%). Regarding the impedance, symptom-association probability was positive in 11.8% of patients. The patients also had higher alkaline reflux rates (6% vs. 0%); additionally, 50% of them experienced belching based on the questionnaire, and 25% had esophagitis based on gastroscopy. Furthermore, patients had a significantly higher number of gas reflux (123.24 ± 80 vs. 37.2 ± 21.5, P = 0.001) and supragastric/ gastric belches (182 ± 64/228 ± 66.69 vs. 25.08 ± 15.20/12.17 ± 17.65, P = 0.001). Supragastric belching was more frequent than gastric belching in the controls, whereas gastric belching was more frequent in the patients. CONCLUSION: Belching increases after gastric bypass surgery in a long-term period. Gastric belching was more frequent than supragastric belching in these patients.

Assessment of prognostic and diagnostic value of some biomarkers in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is an increasing problem worldwide. Determining a prognosis is important for the management of HCC. AIM: We aimed to investigate the impact of interleukin (IL)-29, galectin-3, leptin, fibronectin and protease-activated receptor-1 on the prognosis and diagnosis of patients with HCC. MATERIALS AND METHODS: 60 HCC patients (75% male) and 20 healthy volunteers (70% male) were enrolled in this prospective study. Serum samples were obtained during the first admission before any adjuvant or metastatic treatments were administered. Serum biomarkers were determined using ELISA kits. RESULTS: All patients had cirrhosis, and the Child - Pugh stages were as follows: 61.5% Child - Pugh A, 35.9% Child - Pugh B and 2.6% Child - Pugh C (61.7% hepatitis B virus, 11.7% hepatitis C virus, 6.7% hepatitis B virus + hepatitis C virus, 11.7% alcoholic and 8.3% cryptogenic). Fifty-three percent of the HCC patients died within a median of 7.5 months. The mean serum level of IL-29 in patients with HCC was higher than that in the control group (32.55 pg/ml vs 11.46 pg/ml, p < 0.015). Galectin-3 levels were significantly higher in the HCC group (6.7 ng/ml vs 1.38 ng/ml, p < 0.001). Fibronectin levels were higher in the control group than in the HCC group (260 635 ng/ml vs 257 353 ng/ml). However, the mean protease-activated receptor-1 and leptin levels were similar between the two groups (p > 0.05). The biomarkers were divided into two groups according to their median level. In the log rank analysis, biomarkers had no effect on survival (p > 0.05). CONCLUSIONS: IL-29 and galectin-3 levels were significantly higher in HCC patients. Although IL-29 and galectin-3 can be used as diagnostic markers for HCC, they had no prognostic value in HCC patients.

Should we worry about incidental gastrointestinal tract involvement in positron emission tomography/computed tomography as gastroenterologist?

BACKGROUND AND AIM: Positron emission tomography/computed tomography(PET/CT) scans detects benign clinical conditions in addition to malignancy, and this leads to additional investigation and expenditure. The purpose of our study was to assess the endoscopic and histopathologic results of incidental 18F-FDG uptake in the GI tract. PATIENTS AND METHOD: We enrolled 110 patients who underwent gastroscopy/colonoscopy for incidental GI tract involvement in PET/CT. Histopathologic and endoscopic results were compared with FDG uptake level, pattern of uptake(diffuse/focal), and site of involvement. RESULTS: In our study, 52.7% of the patients were male and the mean age was 57±11 years. Among the participants, 47.3% and 52.7% of patients had upper GI tract and colorectal involvement in PET/CT, respectively. Gastritis and colonic polyps were the most common endoscopic diagnoses that caused FDG uptake in the upper and lower GI tract, respectively. Endoscopic evaluation was normal in 23.6% of patients with pathologic FDG involvement. The rates of adenomatous polyps, malignancy, and hyperplastic polyps were 18.5%, 13.6%, and 6.8%, respectively. The mean SUVmax were higher in malignant lesions than in non-malignant lesions (14.3±8.9 vs. 9.3±5.3)(p=0.02). Diffuse or focal FDG involvement patterns on PET/CT did not help to discriminate malignancy in the GI tract. CONCLUSION: Malignancy was detected in only 13.6% of patients with FDG involvement in the GI tract, and the involvement pattern(diffuse/focal) and SUVmax did not differentiate malignancy.

Double benefit of long-acting somatostatin analogs in a patient with coexistence of acromegaly and ulcerative colitis.

WHAT IS KNOWN AND OBJECTIVE: Somatostatin analogs control GH/IGF-1 excess in acromegaly. Somatostatin receptors also mediate the complex effects of somatostatin on the gastrointestinal tract and may be defensive in inflammatory bowel diseases, such as ulcerative colitis. We present a patient who showed good response to long-acting octreotide (OCT-LAR) treatment in terms of both acromegaly and ulcerative colitis (UC). CASE SUMMARY: A 58-year-old female patient with diagnosis of acromegaly and ulcerative colitis was started on long-acting somatostatin treatment as a first-line treatment for acromegaly as she refused to undergo transsphenoidal surgery. During the follow-up period, a significant amelioration was also observed in the course of ulcerative colitis, and clinical remission of both diseases was achieved uneventfully. WHAT IS NEW AND CONCLUSION: Somatostatin appears to be a promising candidate in the treatment of inflammatory bowel diseases.

Can Helicobacter pylori be eradicated with high-dose proton pump inhibitor in extensive metabolizers with the CYP2C19 genotypic polymorphism?

Proton pump inhibitors (PPI) metabolism and pharmacokinetics are regulated by cytochrome P450 enzymes in the liver. Cytochrome P450 2C19 (CYP2C19) polymorphism plays an import role in the metabolism of PPIs. The three possible genotypes for CYP2C19 each has a distinct effect on the pharmacodynamics of PPIs. Homozygote extensive metabolizers (HomEM) are the most frequent genotype and have two wild-types (non-mutant) (*1/*1) alleles. HomEM is associated with increased enzyme activity, which increases the rate of PPI metabolism. Intragastric pH, which is required for eradication, is lowest in HomEM. In HomEMs, an insufficient increase in intragastric pH results in decreased anti-Helicobacter pylori (HP) efficacy of the antibiotics and, therefore, lower eradication rates. We determined whether the HP eradication rate would increase after high-dose PPI treatment of extensive PPI metabolizers who had been treated unsuccessfully with a standard PPI dose. In our report, increasing the PPI dosage in patients with genotype polymorphisms may be effective on eradication rates. Eradication rates are directly affected by CYP2C19 polymorphisms, and eradication treatments should be planned considering such genotypic polymorphisms. Hence, CYP2C19 genotyping prior to treatment may facilitate determination of the optimum PPI dose to improve the therapeutic outcome. However, further researches are required to confirm this hypothesis.

Effect of retinyl acetate on transglutaminase 2 activity in carcinogen treated rat liver.

Transglutaminase 2 (TG2) has been implicated in wound healing, cellular differentiation, apoptosis and cell survival. TG2 activity increases following acute and chronic liver injury; however, the role of TG2 in tumors, is controversial. TG2 is a retinoid-inducible enzyme. We investigated the effects of retinyl acetate (RA) on the activity and levels of TG2 during the initiation and promotion stages of liver cancer. p-Dimethylaminoazobenzene (p-DAB) was used as initiator and 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) was used as promoter in our model of carcinogenesis. Rats were divided into four groups of 24: control, corn oil control, p-DAB + TCDD, and p-DAB + TCDD + RA. Six rats from each group were sacrificed at days 30, 60, 90 and 120. TG2 activity decreased in the p-DAB + TCDD treated group, but TG2 immunostaining scores did not change by days 90 and 120. Neither TG2 enzyme activity nor the immunostaining score of TG2 protein changed in the tissues of the p-DAB + TCDD + RA group by days 90 and 120. TG2 activity was not be ameliorated by RA during the initiation or promotion stages of carcinogen induced liver cancer.

Steroid-refractory inflammatory bowel disease is a risk factor for CMV infection.

OBJECTIVE: Patients with inflammatory bowel disease (IBD) show increased the prevalence of cytomegalovirus (CMV) infection due to the severity of the disease and the immunosuppressive treatments they receive. The aim of this study was to determine the prevalence of CMV infection in IBD patients and identify the risk factors for CMV infection with different demographic characteristics in IBD patients. PATIENTS AND METHODS: We enrolled 85 patients diagnosed with IBD (43 with ulcerative colitis (UC) and 42 with Crohn's disease (CD)) in this prospective study. The clinical disease activities of UC and CD were assessed using Truelove-Witts and Crohn's disease activity index (CDAI). CMV infection was assessed by detection of DNA using real-time polymerase chain reaction (PCR) in blood samples and quantitative PCR in colonic biopsy specimens and by detection of inclusion bodies using hematoxylin-eosin staining. RESULTS: Thirteen patients with IBD exhibited concomitant CMV infection. CMV infection was not detected in any of the patients in remission. Viral loads measured in the colonic mucosa of infected patients ranged from 800-7000 genome copies/mL total extracted DNA. The mean serum CMV DNA level was 1694 ± 910 copies/mL (range: 800-3800). The rate of steroid resistance in CMV-positive cases was significantly higher than that in CMV-negative cases (p = 0.001). CD with acute exacerbation was a risk factor for CMV disease (p = 0.04). All of the CMV-positive patients received immunosuppressive treatments. CONCLUSIONS: CMV infection should be suspected in steroid-resistant UC and CD. Antiviral treatment improved the clinical outcome in steroid-resistant IBD cases with serum CMV DNA levels above 1000 copies/mL.

Effect of cytochrome P450 2C19 polymorphisms on the Helicobacter pylori eradication rate following two-week triple therapy with pantoprazole or rabeprazole.

OBJECTIVE: Cytochrome P450 2C19 (CYP2C19) polymorphisms play an important role in the metabolism of proton pump inhibitors. Rabeprazole is primarily metabolized via non-enzymatic pathways. In this study, we determined whether rabeprazole- and pantoprazole-based eradication treatments were influenced by CYP2C19 polymorphisms. PATIENTS AND METHODS: A total of 200 patients infected with Helicobacter pylori were treated with either 40 mg of pantoprazole or 20 mg of rabeprazole plus 500 mg of clarithromycin, 1000 mg of amoxicillin twice daily for 2 weeks. CYP2C19 genotype status was determined by Polymerase Chain Reaction (PCR)-restriction-fragment-length polymorphism. The genotypes of cytochrome P450 2C19 were classified as homozigote extensive metabolizer (HomEM), heterozigote metabolizer (HetEM) and poor metabolizer (PM). The CYP2C19 genotype of all patients, the effectiveness of the treatment, the effect of the genotypic polymorphism on the treatment were assessed. RESULTS: The frequencies of HotEM, HetEM, PM were 78%, 19.5% and 2.5%, respectively. 48% (n = 96) of the patients received treatment with rabeprazole and 52% (n = 104) with pantoprazole. The eradication rate was 64.7% for HomEM, 79.4% for HetEM, 100% for PM (p = 0.06). In HetEM, PM, are considered as a single group, the eradication rates were higher in patients with the HetEM and PM (HetEM+PM) genotypes than in those with the wild-type genotype (81.8 vs. 64.7% p = 0.031). Among the patients treated with rabeprazole, the eradication rates were significantly lower in those with the HomEM genotype than in those with the HetEM+PM genotypes (60% vs. 85.7% p = 0.023). CONCLUSIONS: The genotypic polymorphism is effective on the rate of eradication. Eradication treatment rate with rabeprazole is influenced by CYP2C19 genotype.

Melatonin may have a role in the pathogenesis of functional dyspepsia in males.

OBJECTIVE: Pathogenesis of functional dyspepsia (FD) is complex. Melatonin is synthesized in enterochromaffin cells (EC) of the digestive system. It may influence gut function. The aim of this study is to evaluate the serum melatonin levels in FD patients. PATIENTS AND METHODS: A total of 57 FD patients, and 12 healthy controls were enrolled in this study between 2008-2010 years. Diagnosis of FD was established based on the Rome III Criteria. Blood samples were taken at 10 a.m. and serum samples were stored in -85°C. Serum melatonin levels were determined by an enzyme-linked immunosorbent assay (ELISA) kit. (polyclonal Kennaway G280 anti-melatonin antibody, Bühlmann Laboratories AG, Schönenbuch, Switzerland). RESULTS: Twenty-three (40.3%) patients were male, and, mean age was 44.3 ± 12.1 years. Mean age of control group was 38.5 ± 11.8 years, and 7 of them were male. The mean serum concentration of melatonin in patients and control group were 31.19 ± 43.4 pg/ml and 14.8 ± 20.9 pg/ml, respectively (p < 0.05). Melatonin levels were significantly higher in male patients (38.6 ± 55 pg/ml vs 12.8 ± 22 pg/ml, p < 0.05). However, melatonin levels were similar in females (p > 0.05). CONCLUSIONS: The serum melatonin levels were significantly higher in male patients with functional dyspepsia. High nocturnal melatonin secretion may play a role in the pathogenesis of functional dyspepsia, especially in males.

Targeting tachykinin receptors for the treatment of functional gastrointestinal disorders with a focus on irritable bowel syndrome.

BACKGROUND: Tachykinins (TKs) are a family of endogenous peptides widely expressed in the central and in the peripheral nervous systems as well as in the gastrointestinal (GI) tract. They act as full agonists at three different membrane receptors neurokinin (NK) 1, NK2, and NK3, which are G protein-coupled receptors and in the GI tract are expressed both on neurons and effector cells. PURPOSE: This article reviews the literature concerning the role of TKs in the GI tract function in physiological and pathological conditions and their potential relevance in the treatment of functional GI disorders with particular reference to irritable bowel syndrome (IBS). The efficacy of NK1 antagonists in chemotherapy-induced and postoperative nausea and vomiting is well established. While pharmacodynamic studies have reported conflicting and negative results concerning the effects of NK1 and of NK3 antagonists, respectively, on the GI tract function in humans, clinical studies applying the NK3 antagonist talnetant in IBS-D were negative. Pharmacodynamic studies applying NK2 antagonists have suggested a role for antagonism of NK2 receptors in modulation of GI chemical-induced altered motility and of stress-induced altered bowel habits. Clinical studies and in particular a recently completed Phase 2 study have reported that the NK2 antagonist ibodutant is effective and safe in treating symptoms of D-IBS, especially in females.

Infliximab in inflammatory bowel disease: attention to adverse events.

OBJECTIVE: To assess the efficacy and adverse effects of infliximab in patients with Crohn's disease and ulcerative colitis who are resistant to conventional therapy or having fistulising type Crohn's disease. PATIENTS AND METHODS: The patients with a diagnosis of inflammatory bowel disease received infliximab between 2007 and 2009 were followed-up prospectively. Infliximab 5 mg/kg was given at week 0, 2, 6, and every 8 weeks thereafter. Early and late adverse events occurring during the treatment were recorded for each patient. RESULTS: There were 36 patients [mean age 35±12, 17 male] included in the study. Thirty-two (88%) patients were receiving concomitant long-term immunosuppressive therapy. Complete or partial response was obtained in 75% of all patients. At least one adverse event was observed in 10 (28%) patients. Anaphylaxis was seen in 2 (6%) patients, mild acute infusion reaction in 2 (6%) patients, hypotension in 2 (6%) patients, respiratory distress in 2 (6%) patients, skin rash and eruptions in 2 (6%) patients, one hypertension (3%) and one (3%) tightness in the chest. Treatment was continued in all except patients with anaphylaxis. No infection, tumour or cases of death were observed. CONCLUSIONS: Several adverse events might be observed in patients who receive infliximab. Care should be given to patients whom treatment was restarted after a break in regard to anaphylaxis. No serious adverse event was observed during infliximab treatment except allergic events.

Treatment failure may lead to accelerated fibrosis progression in patients with chronic hepatitis C.

Chronic hepatitis C (CHC) patients with treatment failure (TF) remain at risk of continuing fibrosis progression. However, it has not been investigated whether there is an increased risk of accelerated fibrosis progression after failed interferon-based therapy. We aimed to investigate long-term influence of TF on fibrosis progression compared with untreated patients with CHC. We studied 125 patients with CHC who underwent paired liver biopsies from 1994 to 2012. Patients with advanced fibrosis were excluded from the analysis. Sixty-three patients had TF, and 62 patients were treatment-naïve (TN). Annual fibrosis progression rate (FPR) was calculated, and significant fibrosis progression (SFP) was defined as ≥ 2 stage increase in fibrosis during follow-up. Multiple regression analyses were performed to find out independent predictors of FPR and SFP. Demographic characteristics and duration between paired liver biopsies were similar in TF and TN groups. Baseline alanine aminotransferase and gamma-glutamyl transferase (GGT) levels (71 ± 31 vs 47 ± 22, P < 0.001 and 49 ± 39 vs 36 ± 28, P = 0.027, respectively), baseline mean fibrosis stage (2.2 ± 0.7 vs 1.9 ± 0.7, P = 0.018) and histologic activity index (6.3 ± 1.9 vs 4.3 ± 1.6, P < 0.001) were higher in the TF group compared with the TN group. In regression analyses, the strongest independent predictor of fibrosis progression was the GGT level (OR: 1.03, 95%CI 1.01-1.5, P < 0.001). Treatment experience (OR: 5.97, 95%CI 1.81-19.7, P = 0.003) also appeared as an independent predictor of both FPR and SFP. Failed interferon-based CHC treatment may lead to accelerated FPR in the long-term compared with the natural course.

Clinical significance of serum circulating insulin-like growth factor-1 (IGF-1) mRNA in hepatocellular carcinoma.

The principal aim of our study was to investigate the usefulness of serum protein and circulating mRNA of insulin-like growth factor-1 (IGF-1) as a diagnostic and prognostic tool in hepatocellular carcinoma (HCC). Fifty-four HCC patients and age- and sex-matched 20 healthy controls were enrolled into this study. Pretreatment serum IGF-1 and IGF-1 mRNA were determined by the solid-phase sandwich ELISA and quantitative RT-PCR method, respectively. The median age at diagnosis was 60 years, range 36-77 years; where majority of group were male (n = 48, 88.8%). All patients had cirrhotic history. Forty-six percent (n = 25) of patients had Child-Pugh score A, 30% (n = 16) had score B or C. All of the patients were treated with local therapies and none of them received sorafenib. The baseline serum IGF-1 mRNA levels were significantly higher in HCC patients than in the control group (p = 0.04), whereas no significant difference was observed for IGF-1 protein levels between the two group (p = 0.18). Patients with history of HBV infection, who were not treated, and who received multiple palliative treatment for HCC had higher serum IGF-1 mRNA levels (p = 0.03, 0.03, and 0.05, respectively). Poor performance status (p < 0.001), viral etiology of cirrhosis (p = 0.03), larger tumor size (p = 0.01), lower serum hemoglobin levels (p = 0.03), and not be treated for HCC (p = 0.001) related to worse survival. However, neither serum IGF-1 nor serum IGF-1 mRNA had significantly adverse effect on survival (p = 0.53 and 0.42, respectively).

Clinical significance of serum hepatocyte growth factor (HGF) levels in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the commonest primary malignant cancer of the liver in the world. This study was conducted to investigate the serum levels of hepatocyte growth factor (HGF)in HCC patients and the relationship with tumor progression and known prognostic parameters. Fifty-four patients with HCC were investigated. Pretreatment HGF levels were employed the quantitative sandwich enzyme immunoassay technique (ELISA). Age and sex matched 20 healthy controls were included in the analysis. The median age of the patients was 60 years (range 36-77 years); where males consistituted of majority of the group (88.8%). All of patients had cirrhotic history. Fourty-six percent (n = 25) of patients had Child-Pugh Score A, 30% (n = 16) had Score B or C. All of the patients were treated with local therapies but none of them received sorafenib. The baseline serum HGF levels were significantly higher in patients with HCC than in the control group (p < 0.001). Male patients had higher serum HGF levels compared with female patients (p = 0.01). Serum HGF levels were significantly higher in the patients with elevated serum ALT levels than others with normal serum ALT levels (p = 0.05). Poor performance status (p < 0.001), viral etiology of cirrhosis (p = 0.03), larger tumor size (p = 0.01), lower serum hemogloblin levels (p = 0.03), and not be treated for HCC (p = 0.001) related to worse survival. However, serum HGF did not have significantly adverse effect on survival (p = 0.58). Despite serum HGF levels were found diagnostic value, serum HGF levels had no prognostic value in patients with HCC.

Influence of a neurokinin-1 receptor antagonist (aprepitant) on gastric sensorimotor function in healthy volunteers.

BACKGROUND: Substance P (SP) is a member of the neurokinin (NK) family and is one of the established neurotransmitters in the mammalian central and enteric nervous system. It is unclear whether NK1 receptors are involved in the control of gastric sensorimotor function in man. METHODS: We studied the effects of aprepitant, an NK1 receptor antagonist used in the treatment of chemotherapy-induced emesis, on gastric sensorimotor function in healthy volunteers. Sixteen healthy volunteers (six males, 32.4 ± 2.7 years) were studied on three separate occasions after placebo, aprepitant 80 or 125 mg in randomized double-blind study to assess gastric compliance, perception to isobaric distensions, and gastric accommodation with a gastric barostat. KEY RESULTS: Compared to placebo, both doses of aprepitant did not influence gastric compliance or sensitivity to gastric distension. Aprepitant 80 and 125 mg did not have any significant effects on gastric accommodation compared with placebo (mean postprandial gastric volume increase, respectively, 83.4 ± 28.4 vs 35.3 ± 16.2 vs 83.9 ± 30.4 mL, NS). Postprandial gastric compliance and sensitivity to distention were also not altered. CONCLUSIONS & INFERENCES: In health, NK1 receptors do not appear to be involved in the control of gastric compliance, accommodation or sensitivity to distention in man.

Late effects of renal transplantation on endothelial functions and cardiac morphology.

BACKGROUND: Endothelial dysfunction is common in patients undergoing hemodialysis (HD), and cardiovascular morbidity and mortality are higher in these patients. In this study, we evaluated the late posttransplantation effects of cyclosporine and tacrolimus on endothelial function, inflammation, and cardiac architecture. METHODS: The study included 12 patients undergoing hemodialysis (group 1); 22 renal transplant recipients, of which 13 were receiving cyclosporine therapy (group 2) and 9 were receiving tacrolimus therapy (group 3); and 12 healthy control individuals (group 4). Kidney recipients were included if the transplantation procedure had been performed at least 1 year before the study. Asymmetric dimethylarginine, C-reactive protein, carotid intima-media thickness, left ventricular posterior wall thickness, interventricular septal thickness, left ventricular muscle mass index, flow-mediated dilation, and nitroglycerine-induced dilation of the brachial artery were evaluated. RESULTS: Serum asymmetric dimethylarginine, C-reactive protein, carotid intima-media thickness, left ventricular posterior wall thickness, interventricular septal thickness, and left ventricular muscle mass index values were significantly higher in patients undergoing HD than in the other 3 groups (P < .05), whereas percent change in flow-mediated dilation and nitroglycerine-induced dilation of the brachial artery was significantly lower (P < .05). CONCLUSION: Patients undergoing HD demonstrate endothelial dysfunction. In the late posttransplantation period, kidney recipients seem to have similar endothelial function and cardiac architecture as in the healthy population. This result may explain the reduction in cardiovascular morbidity and mortality after transplantation in patients undergoing HD. Tacrolimus and cyclosporine have similar effects on endothelial function.

Influence of ghrelin on the gastric accommodation reflex and on meal-induced satiety in man.

Ghrelin increases gastric tone in the fasting state and enhances gastric emptying in gastroparesis. The aims of the study were to evaluate the effect of ghrelin on postprandial gastric tone and on meal-induced satiety in health. Ten healthy volunteers underwent a barostat study on two occasions. After determination of intra-abdominal pressure (minimal distending pressure, MDP), isobaric volume measurement was performed for 90 min at MDP + 2 mmHg. After 20 min, ghrelin (40 microg) or saline was administered i.v. over 30 min in a double-blind-randomized cross-over design, followed 10 min later by a liquid meal (200 mL, 300 kcal). Stepwise isobaric distentions (+2 mmHg per 2 min) were performed 60 min after the meal. Data (mean +/- SEM) were compared using paired Student's t-test and ANOVA. Separately, a satiety drinking test (15 mL min(-1) until satiety score 5) was performed on 10 subjects twice, after treatment with placebo or ghrelin. Ghrelin infusion significantly inhibited gastric accommodation (mean volume increase adjusted means 108.0 +/- 50 vs 23.0 +/- 49 mL, P = 0.03, ANCOVA with the premeal postinfusion volume as covariate) and reduced postprandial gastric volumes (197.2 +/- 24.6 vs 353.5 +/- 50.0 mL, P = 0.01). Pressures inducing perception or discomfort during postprandial gastric distentions were not altered. During satiety testing, ghrelin did not alter nutrient volume ingested till maximal satiety (637.5 +/- 70.9 vs 637.5 +/- 56.2 mL, ns). Ghrelin administered during the meal significantly inhibits gastric accommodation in health, but this is not associated with early satiation.

Epidural extension of a lumbar vertebral haemangioma.

Vertebral haemangiomas are relatively common, but those extending into the epidural space are rare. A 59-year-old man with severe lower back and right leg pain that did not resolve with conservative treatment was seen in an outpatient clinic. Magnetic resonance imaging of the lumbar spine identified an L3 vertebral corpus lesion with epidural extension. The diagnosis was unclear, so the patient underwent surgery. The pathologic diagnosis was capillary haemangioma, so angiography-guided embolization was performed postoperatively. Vertebral haemangioma must be considered when there is evidence of a vertebral corpus lesion with epidural extension on magnetic resonance imaging.