Numerical aberrations of chromosomes 16, 17, and 18 in hepatocellular carcinoma: a FISH and FCM analysis of 20 cases.
Kato A. Kubo K. Kurokawa F. Okita K. Oga A. Murakami T.
First Department of Internal Medicine, Yamaguchi University School of Medicine, Ube, Japan.
Conventional cytogenetic studies have demonstrated frequent abnormalities of specific chromosomes in hepatocellular carcinoma, although there are few reports examining the relationship between chromosomal aberrations and clinicopathologic features. In this study, numerical aberrations of chromosomes 16, 17, and 18 were examined by fluorescence in situ hybridization using pericentromeric DNA probes in 20 cases of surgically removed hepatocellular carcinoma. DNA ploidy analysis was also performed by flow cytometry. Numerical abnormalities of chromosomes 16, 17, and 18 were found in 7 of 19 cases, 15 of 20 cases, and 12 of 20 cases, respectively. Gain and/or loss of more than one chromosome was detected in 16 of 19 cases. However, aneuploidy was seen in only 9 of 20 tumors by flow cytometry. The incidence of aneusomy 17 and 18 increased with tumor size and stage progression. Fluorescence in situ hybridization analysis demonstrated that numerical chromosomal aberrations accumulated with tumor progression in hepatocellular carcinoma.
Comparison of rapid office-based serology with formal laboratory-based ELISA testing for diagnosis of Helicobacter pylori gastritis.
Kroser JA. Faigel DO. Furth EE. Metz DC.
Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia 19104, USA.
Accurate and cost-effective diagnosis of Helicobacter pylori gastritis has taken on major importance. Several serologic tests for the diagnosis of H. pylori infection are commercially available. We compared the performance of the FlexSure HP rapid IgG antibody test with the conventional HM-CAP ELISA to evaluate whether qualitative office-based serology is reliable enough to replace formal laboratory-based testing. We assessed H. pylori status by concordance in 100 consecutive patients with antral biopsy, rapid urease, and 1 microCi[14C]urea breath tests. Both antibody tests had good sensitivity and specificity (>86%). Concordance between the two antibody tests occurred in 87/93 patients (94%). Based on our data, the office-based FlexSure HP performed equally well as the laboratory-based formal ELISA and may be a better choice for initial serologic diagnosis in untreated patients.
Histamine and tissue fibrinolytic activity in duodenal ulcer disease.
Ben-Hamida A. Adesanya AA. Man WK. Spencer J.
Department of Surgery, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Patients with duodenal ulcer have lower gastroduodenal mucosal histamine and a reduced tissue fibrinolysis at the ulcer edge. In the duodenal mucosa fibrinolysis is regulated by the tissue-type and urokinase-type plasminogen activators; and inhibitors type 1 and type 2. Trends across ordered groups leading from mucosa of nonulcer control subjects, "normal" mucosa of ulcer patients, to ulcer edge were found in tissue-type plasminogen activator concentration, histamine concentration, and histamine methyltransferase activity. Concentrations of tissue-type activator, inhibitor type 1, and histamine were significantly lower at ulcer edge than at normal. An inverse correlation was found between histamine methyltransferase and plasminogen activator activities, methyltransferase and tissue-type activator, and methyltransferase and histamine. These results support the hypothesis that in active ulceration, reduction in tissue fibrinolytic activity is closely associated with enhanced release and metabolism of histamine.
Management of lactose maldigestion by consuming milk containing lactobacilli.
Lin MY. Yen CL. Chen SH.
Department of Food Science, National Chung Hsing University, Taichung, Taiwan.
The influence of nonfermented milk containing L. acidophilus or L. bulgaricus on lactose utilization by lactose maldigesters was investigated. Nonfermented milks containing L. acidophilus or L. bulgaricus at 10(8) and 10(9) CFU/ml were prepared using 2% low-fat milk. Lactose maldigestion was monitored by measuring breath hydrogen at hourly intervals for 8 hr following consumption of 400 ml of each diet. Nonfermented milk containing L. acidophilus B at 10(8) CFU/ml were not effective in reducing breath hydrogen and symptoms. Nonfermented milk containing L. acidophilus B at 10(9) CFU/ml only slightly decreased breath hydrogen production; however, the symptoms were significantly improved. Nonfermented milks containing L. bulgaricus 449 at 10(8) and 10(9) CFU/ml were effective in reducing breath hydrogen and symptoms. The results for bulgaricus milk were all significant. In this study, L. acidophilus B and L. bulgaricus 449 were chosen because of their similar beta-galactosidase activity and bile sensitivity. L. acidophilus and L. bulgaricus are both thermophilic lactobacilli and an active transport (permease) system is found in both species for lactose transport. The major factor affecting in vivo lactose digestion in this study appears to be the bacterial cell wall/membrane structures. That the cell wall/membrane structures of L. acidophilus are different from those of L. bulgaricus can be indirectly proven by the results of sonication time for maximum beta-galactosidase activity measurement. The results of this study indicate that L. bulgaricus is usually a better choice than L. acidophilus for manufacturing nonfermented milks for lactose maldigesters.
Quantitative analysis of ras gene mutation in pancreatic juice for diagnosis of pancreatic adenocarcinoma.
Tada M. Teratani T. Komatsu Y. Kawabe T. Shiratori Y. Omata M.
Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
It has recently been demonstrated that mutant ras gene was also detected in patients with mucinous cell hyperplasia without adenocarcinoma, indicating that the presence of the mutation could not be a definite marker for pancreatic adenocarcinoma. The present study was performed to differentiate pancreatic adenocarcinoma from others by quantification of mutant ras gene in pancreatic juice. By measuring mutant ras gene by polymerase chain reaction (PCR) during its logarithmic phase, the amount was semiquantitatively evaluated between 0.1 and 10% of total DNA that was extracted from pancreatic juice obtained via endoscopy. Semiquantitative analysis revealed that the mutant gene occupied more than 1% of total DNA in eight of 15 patients (53%) with pancreatic adenocarcinoma, and in all three patients (100%) with intraductal papillary neoplasm of the pancreas, but in only two of 19 cases (11%) without neoplasm. Semiquantitative analysis may provide a clinical tool for the differential diagnosis of pancreatic carcinoma.
Majority of gliadin-specific T-cell clones from celiac small intestinal mucosa produce interferon-gamma and interleukin-4.
Troncone R. Gianfrani C. Mazzarella G. Greco L. Guardiola J. Auricchio S. De Berardinis P.
Department of Pediatrics, University Federico II, Naples, Italy.
An abnormal mucosal cell-mediated immune response plays a fundamental role in the pathogenesis of celiac disease. To characterize locally infiltrating T cells, gliadin-specific T-cell clones were isolated from two treated celiac patients. Mucosal biopsies were cultured in vitro for 24 hr with a peptic-tryptic digest (PT) of gliadin. T-cell clones (TCC) were then isolated by limiting dilution. The production of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) was evaluated by ELISA in culture supernatants obtained after a short incubation with anti-CD3 and PMA, or with antigen. Twenty-two TCC were specific for gliadin and/or PT. All were CD3+, CD4+, CD8-, TCR alphabeta+. In one such clone the PT-specific response was inhibited by an anti-DQ, but not by an anti-DR antibody. Of the five gliadin-specific TCC examined, four produced IL-4 and high levels of IFN-gamma; the remaining one initially produced only IL-4, but subsequently also IFN-gamma. All clones obtained from the celiac mucosa, including the gliadin-specific ones, produced high levels of IFN-gamma, in most cases with IL-4. This cytokine profile could explain most of the immunological features of the celiac mucosa.
Colonic luminal hydrogen sulfide is not elevated in ulcerative colitis.
Moore J. Babidge W. Millard S. Roediger W.
University of Adelaide, Department of Surgery, The Queen Elizabeth Hospital, Woodville, Australia.
It has been proposed that the reduction in n-butyrate oxidation by colonic epithelial cells observed in ulcerative colitis may be related to exposure to reduced forms of sulfur derived from dissimilatory sulfate reduction by luminal microflora. This study aims to compare stool sulfide concentrations in control and colitic subjects. Control subjects had significant colorectal disease excluded by virtue of their selection. Patients with ulcerative colitis were stratified by disease extent and activity, and by salicylate drug use. Stool sulfide was measured using a direct spectrophotometric method on NaOH (free sulfide) and zinc acetate (total sulfide) stool slurries. Fifteen control and 19 colitic subjects were studied. There was no significant difference in stool sulfide between control and colitic patients (free sulfide, control = 0.52 (0.17), colitic = 0.45 (0.10), t = 0.36, P = 0.71, total sulfide, control = 1.33 (0.21), colitic = 0.96 (0.15), t = 1.44, P = 0.16). Disease extent or activity did not significantly influence stool sulfide. These results do not support a primary etiologic role for luminal sulfide in ulcerative colitis.
Gastric transit and pharmacodynamics of a two-millimeter enteric-coated pancreatin microsphere preparation in patients with chronic pancreatitis.
Bruno MJ. Borm JJ. Hoek FJ. Delzenne B. Hofmann AF. de Goeij JJ. van Royen EA. van Leeuwen DJ. Tytgat GN.
Department of Nuclear Medicine, Academic Medical Center, Amsterdam, The Netherlands.
It has been suggested that enteric-coated pancreatin microsphere (ECPM) preparations with sphere sizes larger than 1.7 mm pass through the stomach at a slower rate than a meal and therefore may be less efficacious in restoring pancreatic enzyme activity than preparations with smaller sphere sizes. The aim of this study was to investigate the gastric transit profile of a 2-mm ECPM preparation in relation to that of a solid meal and to simultaneously measure enzyme activities in eight patients with pancreatic exocrine insufficiency due to chronic pancreatitis. Gastric transit was assessed by double-isotope scintigraphy. A pancake was labeled with 99mTc. A 2-mm ECPM preparation was labeled with 171Er. Intraluminal pancreatic enzyme activities were assessed during a 6-hr period with the cholesteryl-[14C]octanoate breath test (for carboxyl ester lipase activity) and the N-benzoyl-L-tyrosyl-p-aminobenzoic acid/p-aminosalicylic acid (NBT-PABA/PAS) test (for chymotrypsin activity). The ECPM preparation passed through the stomach more rapidly (median 24 min) than the pancake (median 52 min, P < 0.05). During ECPM therapy, mean cumulative 14CO2 outputs rose significantly from 30% to 70% (P < 0.05), but remained below outcomes in healthy volunteers. Mean cumulative plasma PABA concentrations rose significantly from 46% to 87% (P < 0.05) and were not significantly different from outcomes in healthy volunteers. In chronic pancreatitis, a 2-mm ECPM preparation does not pass through the stomach more slowly than a solid meal, but in fact faster. Digestion of ester lipids and proteins showed an improvement to subnormal and normal levels, respectively.
Serum vascular endothelial growth factor levels in various liver diseases.
Akiyoshi F. Sata M. Suzuki H. Uchimura Y. Mitsuyama K. Matsuo K. Tanikawa K.
Second Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan.
The clinical significance of circulating vascular endothelial growth factor (VEGF) in patients with various liver diseases was investigated. Twenty-one patients with acute hepatitis (AH), 40 with chronic hepatitis (CH), 34 with cirrhosis (LC), 16 with fulminant hepatitis (FH), 10 with primary biliary cirrhosis (PBC), 12 with autoimmune hepatitis (AIH), and 120 healthy individuals were included. Serum VEGF levels were measured by a chemiluminescence enzyme-linked immunosorbent assay. The mean values of serum VEGF levels in the patients with AH, CH, LC, FH, AIH, PBC, and control were 172.7, 58.0, 44.1, 37.3, 49.7, 74.9, and 65.0 pg/ml, respectively. The patients with AH had a level of serum VEGF significantly higher than that of the control group (P < 0.001). The serum VEGF levels in survivors of FH were significantly increased, but not in the nonsurvivors in the recovery phase compared with the levels on admission (P < 0.05). In the LC patients, serum VEGF levels were significantly lower than those of the control group (P < 0.05). These findings suggest that serum VEGF level may be associated with hepatocyte regeneration grade.
Ultrasound-guided liver biopsy for parenchymal liver disease: an economic analysis.
Younossi ZM. Teran JC. Ganiats TG. Carey WD.
Department of Gastroenterology, The Cleveland Clinic Foundation, Ohio 44195, USA.
The use of ultrasound (US) to assist in liver biopsy for nonfocal liver disease has been shown to significantly decrease the incidence of minor complications (defined as pain requiring treatment, hypotension, or bleeding). In this study, decision analysis was used to estimate the average additional net charge for US guidance. The risks for minor and major complications were extracted from the literature. The incidence of minor complications such as pain and bleeding not requiring hospitalization has been reported as 49% for blind liver biopsy and 39% for US-guided liver biopsy. Major complications requiring hospital admission occur in 4% of blind liver biopsies and 2% of US-guided liver biopsies. A decision tree was used to calculate the total charges of liver biopsy and its associated complications. The charge for treating an episode of minor complications was estimated at $605. The charge related to an episode of major complications was estimated at $1533. The total charge for an ultrasound-guided liver biopsy (except the added charge for the use of ultrasound) was $1770, or $102 less than the same charge for blind liver biopsy. The addition of ultrasound in performing liver biopsies for diffuse parenchymal liver disease is cost-saving if the additional charge of US is less than $102.
Arterial-venous shunting in liver cirrhosis.
Molino G. Bar F. Battista S. Torchio M. Niro AG. Garello E. Avagnina P. Fava C. Grosso M. Spalluto F.
Division of General Medicine A and Centro di Informatica Medica, S. Giovanni Battista Hospital, Turin, Italy.
Controversial data exist in the literature about the presence and clinical relevance of hepatic arterial-venous shunting. An interesting opportunity for reconsidering the problem has been provided by the use, in the study of liver function, of D-sorbitol, a substance whose first-pass hepatic extraction is very high in normal subjects, while being directly related to circulatory alterations in liver cirrhosis. Because of this property, the systemic bioavailability of D-sorbitol during hepatic arterial infusion can be assumed to reflect arterial-venous shunting. Thirteen biopsy-proven cirrhotic patients (ages 35-66 years), who required diagnostic arterial catheterization, entered the study. Patients were studied on two subsequent days, in which a sterile pyrogen-free solution (1.5%) of D-sorbitol was administered by direct low-rate infusion (15 mg/min for 20 min) into the hepatic artery and the systemic circulation, respectively. Urine samples were spontaneously collected for 8-hr periods before and during/after each infusion. The hepatic arterial bioavailability of D-sorbitol was calculated as the ratio between the net cumulative urinary outputs of D-sorbitol after infusions into the hepatic artery and the systemic vein. Observed values confirm the existence and the large variability (0-88.7%) of hepatic arterial-venous shunting in cirrhotic patients.
Postperfusion energy metabolism of steatotic graft and its relation to early graft viability following liver transplantation.
Miki C. Iriyama K. Mirza DF. Mayer AD. Buckels JA. Suzuki H. McMaster P.
Department of Surgery II, Mie University Medical School, Tsu, Japan.
The present study was designed to assess energy metabolism of steatotic grafts and to determine its relation to early graft viability. Graft biopsies were taken, and the triglyceride content was determined in 29 grafts for the assessment of steatosis. The peak aspartate aminotransferase level and the concentrations of lactate and pyruvate were strongly correlated with the triglyceride content, suggesting that steatotic grafts are more vulnerable to preservation or reperfusion injury and that glucose oxidation is inhibited postoperatively in the steatotic grafts. Ketogenesis, an alternative pathway to produce energy substrates, was not accelerated even when the steatotic grafts produced more free carnitine to enhance the beta-oxidation of fatty acids. The deterioration of energy metabolism was associated with the increase in prothrombin time ratio, hepatocyte growth factor, and hyaluronic acid that reflected graft viability. Deterioration of postperfusion energy metabolism in the steatotic grafts may be involved in the development of irreversible graft damage.
Expression of protooncogene c-kit and its ligand stem cell factor (SCF) in gastric carcinoma cell lines.
Hassan S. Kinoshita Y. Kawanami C. Kishi K. Matsushima Y. Ohashi A. Funasaka Y. Okada A. Maekawa T. He-Yao W. Chiba T.
Department of Medicine, Kobe University School of Medicine, Japan.
We examined 13 human gastric carcinoma cell lines for the expression of both c-kit and stem cell factor (SCF). Expression of mRNAs was detected by both Northern blot analysis and reverse transcriptase-polymerase chain reaction (RT-PCR), and expression of translated proteins was detected by western blotting. Using RT-PCR we confirmed the expression of c-kit in five (ECC12, TMK1, MKN7, GCIY, and HGC27) cell lines. Northern blot analysis showed coexpression of both c-kit and SCF in ECC12 and expression of SCF in five other (MKN74, MKN1 OKAJIMA, KATOIII, and TMK1) cell lines. SCF stimulated both tyrosine phosphorylation of c-kit and growth of ECC12, whereas it did not stimulate those of GCIY. The sizes of c-kit transcript and protein in GCIY were slightly smaller than those of the reported ones, suggesting the presence of a biologically inactive truncated form of c-kit in GCIY. The present study suggests that c-kit/SCF system might play an important role in the carcinogenesis and tumor growth of ECC12 and that the truncated form of c-kit in GCIY might not be associated with malignant transformation.
Effects of octreotide and erythromycin on gastric myoelectrical and motor activities in patients with gastroparesis.
Chen JD. Lin ZY. Edmunds MC 3rd. McCallum RW.
Lynn Institute for Healthcare Research, Integris Baptist Medical Center, Oklahoma City, Oklahoma 73112, USA.
Simultaneous recordings of gastric manometry and myoelectrical activity were made in 10 patients with gastroparesis. Intravenous erythromycin (100 mg) was administered in the fasting state for a period of 30 min. Subcutaneous injection of octreotide (100 microg) was administered before one of the four identical test meals. It was found that octreotide significantly decreased the antral motility index (30-min fasting: 4.51+/-1.04 vs 1.75+/-0.97, P < 0.02; 60-min fed: 5.16+/-1.44 vs 3.4+/-1.41, P < 0.05) and the dominant power of the EGG (fasting power: 35.19+/-1.54 vs 30.84+/-1.57 dB, P < 0.004; postprandial power increase: 5.52+/-1.06 vs -0.27+/-0.87, P < 0.001). Erythromycin significantly increased the antral motility index (3.16+/-0.96 vs 9.5+/-0.61, P < 0.001) and the dominant power of the EGG (28.86+/-1.57 dB vs 33.55+/-1.59 dB, P < 0.005) in the fasting state. An improvement in the regularity of the gastric slow wave was also noted with erythromycin. It was concluded that: (1) the inhibitory effect of octreotide on postprandial gastric motility and myoelectrical activity suggests that caution should be exercised when octreotide is used in patients with gastroparesis; and (2) the stimulatory effect of erythromycin on gastric myoelectrical activity may enhance gastric motility and gastric emptying in patients with gastroparesis.
Importance of additional reflux events during esophageal acid clearing.
Shay SS. Richter JE.
Gastroenterology Service, Walter Reed Army Medical Center, Washington, DC, USA.
Decreased swallow frequency and low-amplitude or nonconducted primary peristaltic contractions are reported to prolong acid clearing in gastroesophageal reflux disease (GERD) patients. The aim of this study is to investigate which of these, or other factors, have a dominant role in long-duration pH reflux events (pHRE). Simultaneous manometry and pH monitoring was performed for 40 min before and after (beginning 40 min postprandial) a test meal. We arbitrarily chose 180 sec to divide pHREs into long or short pHREs. Twenty GERD patients with and without esophagitis were studied. Esophagitis patients had threefold more long pHREs than patients without esophagitis. In most (56%) long pHREs, additional reflux events during acid clearing was the only finding. Only 11% of long pHREs had either a decreased swallow rate (3%) or decreased peristaltic contraction amplitude (8%), as the only finding contributing to poor acid clearing. However, 18% of long pHREs had one of these peristaltic dysfunctions in combination with additional reflux events prolonging acid clearing. Only 15% of long pHREs had no apparent reason for poor acid clearing. In interpreting 24-hr pH monitoring, one should not assume prolonged acid clearing is due to peristaltic dysfunction; instead, it is often due to additional reflux events.
Augmented eradication rates of Helicobacter pylori by new combination therapy with lansoprazole, amoxicillin, and rebamipide.
Hahm KB. Lee KJ. Kim YS. Kim JH. Cho SW. Yim H. Joo HJ.
Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea.
The aim of the present study was to determine the efficacy of a new combination regimen including an antioxidant, a proton pump inhibitor, and antibiotics against Helicobacter pylori and to document the changes of oxidative stress and cytokines involved in H. pylori-associated gastric inflammation. From 57 patients with endoscopically diagnosed gastric and/or duodenal ulcers associated with H. pylori infection five gastric antral biopsy specimens were taken for the diagnosis of H. pylori and for the experimental measures. The patients were then treated either with lansoprazole 30 mg + amoxicillin 1.5 g (LA group; 21 patients) or lansoprazole 30 mg + amoxicillin 1.5 g + rebamipide 300 mg (LAM group; 36 patients) for two weeks. Four weeks after the initiation of treatment, the patients were endoscoped again and biopsy specimens were obtained. Mucosal malondialdehyde (MDA) levels; myeloperoxidase (MPO) activities; superoxide dismutase; catalase; glutathione peroxidase; cytokines IL-1, IL-6, TNF-alpha; and chemokines IL-8, GRO-alpha, RANTES (regulated on activation normal T expressed and secreted) were measured. Using paraffin-embedded tissue sections, in situ terminal deoxyribonucleotide transferase (TdT) mediated dUTP nick end labeling (TUNEL) for apoptosis and immunohistochemical staining for inducible nitric oxide synthase (iNOS) were performed. Two weeks of treatment with the LA regimen resulted in 57.4% eradication rates of H. pylori, whereas two weeks of treatment with the LAM regimen resulted in 75.0% eradication rates. Eradication rates between these two groups were statistically significantly different (P < 0.05). Mucosal MDA levels and MPO activities were significantly lower in the LAM group than the LA group. Mucosal levels of cytokines IL-1, IL-6, and TNF-alpha and of chemokines IL-8, GRO-alpha, and RANTES were all significantly decreased after the treatment of H. pylori, especially so in the LAM group. The apoptotic index and iNOS score were significantly reduced after the eradication of H. pylori. The addition of an antioxidative drug to the eradication regimen against H. pylori has advantages either in augmenting the eradication rates of H. pylori or in decreasing the oxidative stress and cytokines levels generated by H. pylori infection.
HLA class I and II profiles of patients presenting with Chagas disease.
Deghaide NH. Dantas RO. Donadi EA.
Department of Medicine, School of Medicine of Ribeirao Preto, University of Sao Paulo, Brazil.
To evaluate the HLA class I and II profiles of a large group of patients with Chagas' disease, 176 patients presenting with pure cardiomyopathy with heart failure (N = 60), cardiomyopathy without heart failure (N = 18), pure digestive tract manifestations (N = 25), cardiac plus digestive disease (N = 40), and asymptomatic patients with positive serology for chronic Trypanosoma cruzi infection (N = 33) were studied. A total of 448 normal individuals were also studied in parallel. HLA class I and II specificities were determined using serology and oligonucleotide analysis. HLA-A30 antigen was overrepresented in the total group and in the subgroups presenting with the pure cardiac (with or without heart failure) or digestive form, conferring similar relative risks and etiologic fractions on all these presentation forms. Serologic HLA class II analysis showed that HLA-DQ1 conferred susceptibility to, while HLA-DQ7 antigen conferred protection against the development of the disease in the total group of patients. Oligonucleotide typing did not confirm the HLA class II associations obtained by serology, but showed that HLA-DQB1*06 alleles were underrepresented in the total group and in the subgroups presenting with pure digestive or cardiac disease, conferring closely similar relative risks and preventive fractions. Although asymptomatic patients showed a tendency to increased HLA-A30, they presented a significant increase of HLA-DQB1*0302 specificity. In conclusion, HLA-A30 antigen conferred susceptibility to, while HLA-DQB1*06 specificity conferred protection against, the development of the disease, regardless of the form of presentation, ie, cardiac or digestive tract disease.
Influence of H. pylori infection on gastric motor and sensory function in asymptomatic volunteers.
Saslow SB. Thumshirn M. Camilleri M. Locke GR 3rd. Thomforde GM. Burton DD. Hanson RB.
Gastroenterology Research Unit, Mayo Clinic, Rochester, Minnesota 55905, USA.
The effect of H. pylori infection on gastric motility and sensation is unclear. Our hypothesis is that H. pylori infection increases gastric sensation and reduces gastric accommodation and emptying. In eight H. pylori-positive and eight H. pylori-negative asymptomatic subjects, infection was proven by antral histology or culture. We evaluated: (1) gastric emptying of solids, (2) proximal gastric compliance, (3) fasting and postprandial proximal gastric tone and phasic contractions, (4) gastric sensation during balloon inflations or ingestion of cold water, and (5) abdominal vagal function. H. pylori infection was associated with lower gastric accommodation (median 75% postprandial increase in barostat balloon volume compared to fasting) when compared to the accommodation in uninfected volunteers (median 211% change from fasting). One H. pylori-positive subject had an abnormal abdominal vagal function test and her gastric accommodation response was reduced. Other motor and sensory functions in the two groups were similar. In asymptomatic volunteers, H. pylori infection and gastritis result in reduced accommodation (diastolic dysfunction) but no change in overall sensation or motor functions of the stomach.
Expression of p53 and p21WAF1/CIP1 proteins in gastric and esophageal cancers: comparison with mutations of the p53 gene.
Seta T. Imazeki F. Yokosuka O. Saisho H. Suzuki T. Koide Y. Isono K.
First Department of Medicine, Chiba University School of Medicine, Japan.
The p53 gene has been shown to be commonly mutated in various human cancers, and mutant p53 can act as a dominant oncogene. The intact p53 protein is also known to induce the cyclin-dependent kinase inhibitor p21WAF1/CIP1 and is implicated in cell cycle arrest. We investigated p53 gene alterations in gastric adenocarcinoma and esophageal squamous cell carcinoma to elucidate the association of the nuclear accumulation of the p53 protein and/or p21WAF1/CIP1 protein. Abnormalities of the tumor suppressor gene p53 protein and the expression of p21WAF1/CIP1 protein were analyzed by immunohistochemical techniques in 32 cases of gastric adenocarcinoma and 15 cases of esophageal squamous cell carcinoma. Twenty cases of gastric cancer and five cases of esophageal cancer were also analyzed for p53 gene mutation by polymerase chain reaction and direct nucleotide sequencing. Overexpression of p53 protein was found in 13/32 (41%) of gastric cancers and 5/15 (33%) of esophageal cancers. We found immunodetectable p53 in 10/14 cases with mutations and in none of 11 cases without mutations in gastric and esophageal cancers. Hence, immunohistochemical and genetic analyses gave concordant results in 84% of 25 cases, revealing a good correlation between immunostaining of p53 and missense mutation of the p53 gene. p53 immunostaining was not observed in cases with frameshift or splicing mutation. The expression of p21WAF1/CIP1 protein was found in 9/32 (29%) of gastric cancers and 4/15 (27%) of esophageal cancers and in 2/14 (14%) cases with alteration of the p53 gene and in 5/11 (45%) without. These results suggest that abnormalities of p53 may be closely associated with the pathogenesis of gastric adenocarcinoma and esophageal squamous cell carcinoma and that the immunoreactivity of p53 protein is a general indicator of the tumors with altered p53 function. The expression of p21WAF1/CIP1 protein was suppressed in the neoplastic tissues with and without p53 gene alteration.
Specificity of polymerase chain reaction monoclonality for diagnosis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma: direct comparison to Southern blot gene rearrangement.
Weston AP. Banerjee SK. Horvat RT. Cherian R. Campbell DR. Zoubine MN.
Molecular Gastroenterology and Pancreatic Cancer Research Unit, Veterans Administration Medical Center, Kansas City, Missouri 64128-2226, USA.
The specificity of polymerase chain reaction monoclonality in the diagnosis of gastric lymphoma was prospectively evaluated. Gastric mucosal tissue from normal gastric mucosa (N = 13), benign gastric ulcers (N = 3), chronic Helicobacter pylori gastritis (N = 3), gastric mucosa-associated lymphoid tissue (N = 16), and gastric lymphoma (N = 15) was obtained. Polymerase chain reaction amplification of the heavy-chain framework 2A gene was performed. The sensitivity and specificity of heavy-chain clonality, in the detection of gastric lymphoma, were 73.3% and 45.7%, respectively. Determination of monoclonality by polymerase chain reaction methodology is not an acceptable technique for confirming the diagnosis of gastric lymphoma as it is too sensitive, detecting minute populations of clonal lymphocytes that occur in benign diseases as well as larger populations of clonal lymphocytes associated with malignant gastric lymphoproliferative diseases. Southern blot gene rearrangement testing should be utilized to determine clonality in the evaluation of gastric lymphocytic infiltrates.
Screening for APC mutations based on detection of truncated APC proteins.
Tominaga O. Nita ME. Nagawa H. Muto T.
First Department of Surgery, University of Tokyo, Japan.
Mutation of the adenomatous polyposis coli (APC) gene is frequently found in colorectal tumors from both familial adenomatous polyposis (FAP) and non-FAP patients. Analysis of APC mutation is time-consuming and costly due to the large size of the APC gene. As the majority of APC mutations result in the truncation of gene products, the detection of truncated APC proteins may be used as a screening method for APC mutations. The aim of this study is to establish a practical method of detecting truncated APC proteins for the screening of APC mutations. APC proteins in human colorectal cancer cell lines were analyzed by western blotting. Truncated APC proteins were expressed in all of the colorectal cancer cell lines studied. Two species of truncated APC proteins were expressed in two cell lines. Western blotting is a rapid, reliable screening method for APC mutations and provides information on both alleles.
Prostaglandin levels in human colorectal mucosa: effects of sulindac in patients with familial adenomatous polyposis.
Giardiello FM. Spannhake EW. DuBois RN. Hylind LM. Robinson CR. Hubbard WC. Hamilton SR. Yang VW.
Department of Medicine, Oncology Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Recent evidence suggests that nonsteroidal antiinflammatory drugs (NSAIDs) may prevent colorectal cancer. The mechanism of action of NSAIDs in chemoprevention is unknown but may be linked to their effect on mucosal prostaglandin levels. Levels of five major prostaglandin metabolites were measured by gas chromatography-mass spectrometry in biopsy specimens of flat rectal mucosa from four patients with familial adenomatous polyposis (FAP) before and after sulindac therapy and from five healthy individuals. The prostaglandin present at highest concentration in rectal mucosa from FAP and control subjects was prostaglandin E2. The concentration of thromboxane B2 alone was significantly elevated in FAP patients compared to controls (P = 0.016). In FAP patients treated with sulindac, all prostaglandin metabolite levels were significantly reduced compared to pretreatment levels (P < 0.05) except prostaglandin D2 (P = 0.07). Prostaglandins D2, E2, F2alpha, and 6-keto-F1alpha levels also were significantly reduced in FAP patients on sulindac compared to healthy controls (P < 0.05). However, interpatient heterogeneity of response to sulindac was evident with changes ranging from +19% to -89%, and the patient with the greatest reductions after sulindac developed colorectal cancer after 35 months of therapy. Sulindac treatment, at drug doses shown to regress colorectal adenomas in FAP patients, has heterogeneous effects on the level of major prostaglandins in their rectal mucosa and may not prevent colorectal cancer due to uncoupling of prostaglandin levels and carcinogenesis.
Hepatic perfusion changes after transcatheter arterial embolization (TAE) of hepatocellular carcinoma: measurement by dynamic computed tomography (CT).
Tsushima Y. Unno Y. Koizumi J. Kusano S.
Department of Radiology, National Defense Medical College, Tokorozawa, Saitama, Japan.
We observed the hemodynamic changes at the level of the hepatic parenchyma induced by transcatheter arterial embolization (TAE) for hepatocellular carcinoma in 22 patients. TAE was performed by administration of a mixture of iodized oil, adriamycin, and mitomycin C, followed by injection of gelatin sponge particles (1-mm pieces). Perfusion measurements (arterial and portal) were done by dynamic computed tomography (CT). Arterial perfusion was increased two to six days after TAE (0.146 +/- 0.073 ml/min/ml, P < 0.0002) compared with that before TAE (0.064 +/- 0.039), but decreased again one month after TAE (0.086 +/- 0.038). Portal perfusion was decreased two to six days after TAE (0.541 +/- 0.180, P < 0.001) compared with that before TAE (0.733 +/- 0.263) and was grossly unchanged one month after TAE (0.651 +/- 0.214). We suspected that these perfusion changes were due to acute inflammatory responses. Quantification of tissue perfusion by dynamic CT was useful for studying hemodynamic changes after TAE.
Human gallbladder mucosal function: effects on intraluminal fluid and lipid composition in health and disease.
Ginanni Corradini S. Yamashita G. Nuutinen H. Chernosky A. Williams C. Hays L. Shiffman ML. Walsh RM. Svanvik J. Della Guardia P. Capocaccia L. Holzbach RT.
Department of Gastroenterology and General Surgery, Cleveland Clinic Foundation, Ohio 44195, USA.
Gallbladder mucosal absorption of fluid during fasting is a well-known process. Indirect in vivo and recent in vitro evidence for physiologically relevant gallbladder absorption of cholesterol and phospholipids from bile has been observed in humans. The present study explored and compared by indirect means the relative efficiences of human gallbladder mucosal absorption of fluid and lipids in health and disease. Biliary lipids and pigment content were measured in fasting gallbladder bile samples obtained from gallstone-free controls and from four study groups: multiple and solitary cholesterol gallstone patients, and morbidly obese subjects with and without gallstones. Bile salts and pigment content were significantly greater in gallstone-free controls than in all other disease study groups. This was interpreted as evidence of more effective gallbladder mucosal fluid absorption in nonobese gallstone-free controls compared to that in all other groups. Correlation plot analyses of biliary lipids showed lower concentrations of phospholipids than expected from the index bile salt concentrations. The same was found for cholesterol concentrations but only in supersaturated samples. These findings were much more pronounced in gallstone free-controls and were accordingly interpreted as evidence of more efficient gallbladder absorption of both phospholipids and cholesterol in controls compared with that found in each of the disease study groups. Moreover, impaired gallbladder mucosal function, while invariably associated with cholesterol gallstone disease, was not found to be a necessary consequence of the physical presence of stones. It is concluded that efficient gallbladder mucosal absorption of both fluid and apolar lipids from bile is a normal physiological process that is often seriously impaired in the presence of either cholesterol gallstone disease or at least one of its precursor forms.
Gallbladder volume: comparison of diabetics and controls.
Chapman BA. Chapman TM. Frampton CM. Chisholm RJ. Allan RB. Wilson IR. Burt MJ.
Department of Gastroenterology, Christchurch Hospital, Christchurch School of Medicine, New Zealand.
Diabetics are known to have an increased prevalence of gallstones. The aim of this study was to investigate whether diabetics have increased gallbladder volumes that would predispose to stasis, nucleation of cholesterol crystals, and gallstone formation. The gallbladder volume of 271 diabetic subjects and 277 controls was determined by ultrasound using the ellipse formula. Gallbladder volume was also determined by the sum of the cylinders method in 143 cases with a strong correlation (r = 0.89) between the two methods. Using analysis of variance, gallbladder volume was influenced by both diabetic type (NIDDM = 33.68 cm3, IDDM = 26.84 cm3, controls = 29.05 cm3; P = 0.018) and the presence of gallstones (gallstones = 32.04 cm3, no gallstones = 27.58 cm3; P = 0.018). The variation in gallbladder volume between NIDDM, IDDM, and control subjects was influenced by the presence of gallstones (P = 0.024, interaction term from ANOVA). Significant differences (P < 0.001) were only found between NIDDM vs IDDM and NIDDM vs control in the nongallstone group (NIDDM = 34.33 cm3, IDDM = 25.08 cm3, control = 25.17 cm3). Males had significantly larger gallbladder volumes than females: 31.98 cm3 vs 27.74 cm3 (P = 0.023). After the inclusion of BMI, HDL cholesterol, triglyceride, and age in a statistical model with gender and diabetic type in those without gallstones, significant differences were still found between NIDDM and IDDM (P = 0.013) and NIDDM and controls (P = 0.005), demonstrating that NIDDM is an independent predictor for increased gallbladder volume.
Dissolution of gallstones with simvastatin, an HMG CoA reductase inhibitor.
Chapman BA. Burt MJ. Chisholm RJ. Allan RB. Yeo KH. Ross AG.
Department of Gastroenterology and Radiology, Christchurch Hospital, New Zealand.
The aim of this study was to determine whether 12 months of therapy with Simvastatin, an HMG CoA reductase inhibitor, would dissolve gallstones. Twenty-seven subjects entered the study, all had a fasting oral cholecystogram, ultrasound examination, and fasting serum lipids prior to therapy. In addition, 22 subjects had their gallbladder ejection fraction, after CCK, determined by radionucleotide scanning. Eleven subjects had the cholesterol saturation index (CSI) of bile calculated before and at the end of 12 months of therapy. Of the 27 subjects, 26 completed 12 months of treatment with Simvastatin 20 mg daily. There was a significant fall in the total serum cholesterol (27%, P < 0.0001), LDL cholesterol (31%, P < 0.0001), triglyceride (34%, P < 0.0001) but no change in HDL after 12 months of therapy. Simvastatin treatment resulted in a 28% fall in the CSI of bile at the end of therapy (P < 0.01). The concentrations of individual bile acids did not change with therapy, and apart from a slight but significant increase in arachidonate, there were no other significant changes in the fatty acid composition of the biliary phospholipids. After 12 months of Simvastatin therapy there was a small decrease in the gallstone diameter but complete dissolution of gallstones was not achieved in any subjects. In conclusion 12 months of therapy with Simvastatin was effective in lowering the serum lipids and the CSI of bile but was not effective in dissolving gallstones.
Portal hemodynamics by duplex Doppler sonography in different grades of cirrhosis.
Chawla Y. Santa N. Dhiman RK. Dilawari JB.
Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Not much is known about the relationship between portal hemodynamics and the grades of cirrhosis. Using pulsed Doppler ultrasonography, we studied portal vein diameter, portal flow velocity, and portal blood flow rate in 37 patients with liver cirrhosis (11 Child's A, 13 Child's B, and 13 Child's C) and 10 healthy controls. There was no difference in the maximum inner diameter of the portal vein in cirrhotics and controls. However, there was a significant decrease in the portal flow velocity in patients with Child's C cirrhosis, as compared to controls and patients with Child's A and Child's B cirrhosis. The portal blood flow rate in Child's B and Child's C cirrhosis was also significantly less as compared to controls and patients with Child's A cirrhosis. Patients with ascites and encephalopathy had significantly lower portal flow velocities and blood flow rate as compared to those without ascites and encephalopathy, respectively. This study indicates that portal flow significantly decreased in cirrhotic patients with worsening Child's grade of cirrhosis.
The two different states of hepatitis B virus DNA in asymptomatic carriers: HBe-antigen-positive versus anti-HBe-positive asymptomatic carriers.
Fujiwara K. Yokosuka O. Ehata T. Chuang WL. Imazeki F. Saisho H. Omata M.
First Department of Medicine, Chiba University School of Medicine, Chiba City, Japan.
During the course of hepatitis B virus (HBV) infection, there exists a long period of normal liver function tests with different states of HBeAg/Ab. As the state of HBV in asymptomatic carriers was not well characterized, we quantitatively and qualitatively examined HBV in both HBeAg-positive and anti-HBe-positive asymptomatic carriers. Sera from 10 HBeAg-positive and 27 anti-HBe-positive asymptomatic carriers were analyzed. The amount of HBV DNA was determined by dot-blot hybridization and polymerase chain reaction. The mutations in precore and core regions, spanning 636 nucleotides, of hepatitis B virus were examined by directly sequencing the amplified HBV DNA. HBV DNA was detected in all 10 HBeAg-positive cases, whereas it was found in only 7 of 27 (26%) anti-HBe-positive cases by the nested PCR method. The mean amount of HBV DNA in HBeAg-positive cases was 10(9.1 +/- 0.7) copies/ml, while that in anti-HBe-positive cases was 10(1.0 +/- 1.5) copies/ml. There were no missense mutations in the entire precore and core genes of HBV DNA taken from HBeAg-positive asymptomatic carriers. In contrast, many mutations (mean 9.0 +/- 3.3, range 6-14) were detected in the core gene of seven anti-HBe-positive asymptomatic carriers including two cases with increments of the mutations. Analysis of the precore region revealed three wild-type and four mutant-type (including one coexisting with wild-type) cases. These data suggest that HBV exists in quite different ways in "asymptomatic" carriers; in the HBeAg-positive phase HBV probably coexists with the host and remains as the wild type, whereas in the anti-HBe-positive phase a drastically reduced amount of HBV with many mutations remains, probably as a consequence of the long-lasting interaction with the host. Nevertheless, such small amount of virus could cause fulminant hepatic failure. It is important to make further clinical and virological investigations in order to understand the state of asymptomatic carrier.
Different constitution of hepatitis C virus population in peripheral blood mononuclear cells and plasma in patients with type C chronic liver disease.
Okumura A. Yoshioka K. Aiyama T. Takayanagi M. Iwata K. Ishikawa T. Kakumu S.
First Department of Internal Medicine, Aichi Medical University, Aichi-ken, Japan.
We searched for the presence of the plus or minus strand of hepatitis C virus (HCV) RNA in peripheral blood mononuclear cells (PBMCs) from three patients with chronic HCV infection using the strand-specific reverse transcription and polymerase chain reaction (RT-PCR) method. To examine whether the HCV population of PBMCs differs from that of plasma, a sequence of the hypervariable region (HVR) in the E2/NS1 region was analyzed. All three patients had both plus and minus strands of HCV RNA in their PBMCs. Sequence study revealed that the HCV population in PBMCs was homogeneous in all patients, while that in plasma was composed of two main clones. One of these had the same sequence as the clones seen in PBMCs, except for one patient. Our results suggest that PBMCs represent one of the extrahepatic replication sites of HCV and that tissue tropism is expressed by some of the HCV population.
Comparison of HCV RNA levels by branched DNA probe assay and by competitive polymerase chain reaction to predict effectiveness of interferon treatment for patients with chronic hepatitis C virus.
Hayashi J. Kawakami Y. Nabeshima A. Kishihara Y. Furusyo N. Sawayama Y. Kinukawa N. Kashiwagi S.
Department of General Medicine, Kyushu University Hospital, Fukuoka, Japan.
To compare hepatitis C virus (HCV) RNA levels determined by branched DNA probe assay and by competitive polymerase chain reaction (PCR) as predictive markers of the response to interferon for treatment of patients with chronic HCV infection, we studied data on 140 patients treated for six months with natural interferon-alpha. Serum samples were tested for HCV RNA by PCR. HCV RNA was grouped into four genotypes by PCR with type-specific primers, and HCV RNA level was measured by branched DNA probe assay and by competitive PCR. HCV RNA was detected in all patients prior to initiation of the treatment. A complete response, sustained elimination of HCV RNA, occurred in 51 patients (36.4%). With multiple logistic regression analysis assessment, when using competitive PCR, a low level of HCV RNA (P < 0.0001), younger age (P = 0.0054) and genotype 2a and 2b (P < 0.0158) were significant predictive markers for a complete response to interferon treatment. When using branched DNA probe assay, a low level of HCV RNA (P < 0.0001) and age (P = 0.0089) were predictive markers, but genotype was not. The branched DNA probe assay had a narrower linear range for quantitation of HCV RNA level than competitive PCR. In conclusion, HCV RNA level determined by branched DNA probe assay proved to be useful for prediction of effects of interferon and it is cost effective as a marker of complete response to interferon treatment for patients with chronic HCV infection.
Idiopathic neonatal hepatitis presenting as neonatal hepatic siderosis and steatosis.
Tazawa Y. Abukawa D. Maisawa S. Nishinomiya F. Oyake Y. Takada G. Konno T.
Department of Pediatrics, Akita University School of Medicine, Hondo, Japan.
Idiopathic neonatal hepatitis (INH) is a heterogeneous disease of undetermined cause. We report a retrospective histologic reevaluation of INH. Sixty patients with INH were reviewed along with 32 biliary atresia (BA) patients. Histologic findings, iron and fat deposits, giant cell transformation, portal fibrosis, and bile duct proliferation were semiquantitatively graded from 0 to 4+. Significant histologic findings were defined as > or =2+. Frequencies of patients with significant histologic findings in the INH group were compared with those of the BA group. Among the patients with significant histologic findings, those in the INH group had significantly less iron deposits (P < 0.01), portal fibrosis (P < 0.01), and bile duct proliferation (P < 0.01) than those of the BA group. A combination of significant hepatic macrovesicular steatosis and siderosis was observed in 10 INH patients but not in any BA patient (10/60 vs 0/32, P < 0.05). Without extensive treatment, the 10 INH patients all recovered, and hepatic abnormalities normalized by the age of 12 months. In conclusion, the present study showed that the recognition of hepatic siderosis is helpful to distinguish BA from INH and that in a subset of INH patients hepatic macrovesicular steatosis and siderosis occurs.
Quality of life in persons with irritable bowel syndrome: development and validation of a new measure.
Patrick DL. Drossman DA. Frederick IO. DiCesare J. Puder KL.
Department of Health Services, University of Washington, Seattle 98195-7660, USA.
How irritable bowel syndrome (IBS) and its treatment affect quality of life (QOL) is important. To develop a quality-of-life measure specific to irritable bowel syndrome, items were generated using a conceptual model and qualitative interviews with persons diagnosed using the Rome criteria. Symptom frequency and bothersomeness indices were created. Psychometric evaluation methods involved an initial cross-sectional survey followed by a repeat survey. The resulting 34-item measure demonstrated high internal consistency (Cronbach's alpha = 0.95) and high reproducibility (ICC = 0.86) with average time of seven days (SD = 1). For discriminant validity: number of symptoms (P < 0.05), self-reported severity of symptoms (P < 0.001), and the functional bowel disorder severity index (P < 0.001) significantly predicted IBS-QOL scores. Convergent validity and analyses confirmed predictions that scores are more closely related to psychological well-being (0.45) than to function (0.36). We conclude this measure meets established psychometric criteria for reliability and validity; testing of its responsiveness is warranted.
Crohns disease stable remission after human immunodeficiency virus infection.
Pospai D. Rene E. Fiasse R. Farahat K. Beaugery L. Lammens P. Reimund C. Duclos B. Le Quintrec Y. Vandercam B. Mignon M.
Department of Gastroenterology and Nutrition, Bichat Claude-Bernard University Hospital, Paris, France.
We retrospectively assessed the clinical course in four patients with long-standing Crohn's disease who became infected with human immunodeficiency virus (HIV). The duration of active Crohn's disease was 21, 10, 4, and 4 years in our four patients. They experienced a stable remission of Crohn's disease symptoms after HIV infection. In three patients Crohn's disease was in stable remission for 5, 8, and 8 years after HIV infection and all three died from acquired immunodeficiency syndrome-related disease. One patient was still alive without recurrence of Crohn's disease symptoms 7 years following HIV detection. Our observations of a spontaneous improvement in the clinical course of Crohn's disease after HIV infection, suggests that the integrity of the immune response, especially that of CD4 T cells, plays a major role in the tissue injury mechanism in Crohn's disease.
Disseminated aseptic abscesses associated with Crohns disease: a new entity?
Andre M. Aumaitre O. Papo T. Kemeny JL. Vital-Durand D. Rousset H. Ninet J. Pointud P. Charlotte F. Godeau B. Schmidt J. Marcheix JC. Piette JC.
Department of Internal Medicine, University Hospital Gabriel Montpied, Clermont-Ferrand, France.
Our purpose is to describe seven cases of disseminated aseptic abscesses with regard to clinical, biological, radiological, and histological information, treatment, and outcome. Data were collected on seven Caucasian patients who had proven sterile deep abscesses diagnosed in French university hospitals. The onset of the disease related to abscesses began at times from June 1988 to August 1994. Follow-up periods were 1 year, 7 months to 8 years, 2 months. The age of the patients ranged from 15 to 26 years old. At onset, all had fever and six had abdominal pain. Abscesses involved spleen and abdominal lymph nodes in six cases; liver in three; pancreas, brain, and chest in one. All had polymorphonuclear leukocytosis. Pathological examination showed granulomatous abscesses. Direct and indirect investigations failed to identify any causal microorganism. On six occasions, Crohn's disease was revealed 1 to 41 months later and in one case, it preceded the onset of abscesses. One subsequently developed Sweet's syndrome. Various antibiotic regimes were inefficient. Steroids, associated in three cases with immunosuppressive agents, resulted in a rapid improvement in six patients. In one case, splenectomy followed by 5-ASA therapy was used successfully. The dramatic effectiveness of steroids and immunosuppressive agents as well as follow-up suggest that disseminated aseptic abscesses might be an extraintestinal manifestation of Crohn's disease. Although the pathogenesis of this condition remains unknown, this entity may be related to neutrophilic dermatosis in which sterile deep abscesses have been reported.
Preoperative perfusion of bypassed ileum does not improve postoperative function.
Miedema BW. Kohler L. Smith CD. Phillips SF. Kelly KA.
Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA.
This study evaluated whether twice daily isotonic perfusion of the bypassed ileum for six weeks would enhance its motor activity and its absorption of fluids, electrolytes, and vitamin B12. The study also determined if patients undergoing perfusion had improved bowel function and decreased hospital stay after ileostomy closure. Following proctocolectomy, ileal pouch-anal canal anastomosis, and diverting loop ileostomy, six patients self-infused an isotonic solution (sucrose and sodium chloride) into the bypassed ileum twice daily, while seven patients did not (controls). Two months following proctocolectomy, and just prior to ileostomy closure, a manometric catheter assembly was placed into the unused distal ileum via the stoma and the distal ileum perfused with an isotonic sodium chloride solution for 3 hr during fasting and 3 hr after a meal. Absorption was measured, single and clustered pressure waves were identified, and a motility index was calculated. Water absorption, motility index, and cluster parameters did not improve in perfused patients compared to controls during fasting or after a meal, nor did perfused patients have improved vitamin B12 absorption. The perfused patients also did no better clinically following ileostomy takedown; the onset of bowel movements, their frequency, time to tolerate a diet, and hospital stay were similar to controls. We conclude that six weeks of twice daily isotonic perfusion did not improve motor activity or water, electrolyte, and vitamin B12 absorption in the bypassed distal ileum after proctocolectomy, ileal pouch-anal canal anastomosis, and loop ileostomy. The perfusion also did not improve bowel function after ileostomy takedown.
In vivo and in vitro efficacy of octreotide for treatment of enteric cryptosporidiosis.
Guarino A. Berni Canani R. Spagnuolo MI. Bisceglia M. Boccia MC. Rubino A.
Department of Pediatrics, University Federico II of Naples, Italy.
Previous evidence suggested a role of enterotoxin in the pathophysiology of cryptosporidiosis. If so, antisecretory drugs should be effective in reducing diarrhea. We evaluated the in vivo and in vitro efficacy of octreotide, which possesses antisecretory effects, for cryptosporidial diarrhea. Two children with severe cryptosporidial diarrhea were treated with octreotide. The volume modifications and chemical composition of stools were determined. Fecal supernatant was added to Caco-2 cell monolayers mounted in Ussing chambers with or without serosal octreotide and electrical parameters were monitored. Octreotide was effective in reducing the stool volume and fecal Na+ concentration. Fecal supernatant induced an enterotoxin-like increase in transepithelial potential difference. Octreotide induced a dose-dependent decrease in basal potential difference, consistent with an absorptive effect. In cells pretreated with octreotide, fecal supernatant induced an increase in the potential difference, whose magnitude and duration were significantly reduced compared to untreated cells. These results provide in vivo and in vitro evidence for the secretory nature of cryptosporidial diarrhea and for the efficacy of octreotide through a direct interaction with the enterocyte.
Interleukin-6 and small intestinal luminal immunoglobulins.
Riordan SM. McIver CJ. Wakefield D. Thomas MC. Duncombe VM. Bolin TD.
Department of Gastroenterology, The Prince of Wales Hospital, University of New South Wales, Sydney, Australia.
Our aim was to determine the relationships between interleukin-6 and immunoglobulin levels within small intestinal luminal secretions. Twenty adult subjects with small intestinal bacterial overgrowth (N = 13), irritable bowel syndrome (N = 4), and nonulcer dyspepsia (N = 3) underwent endoscopic aspiration of secretions from the small intestinal mucosal surface for assessment of IL-6, IgA1, IgA2, IgM, IgG1, IgG2, IgG3, and IgG4 concentrations. Serum immunoglobulin concentrations and small intestinal histology were also determined. IgA2 and IgG3 were the predominant IgA and IgG subclasses in luminal secretions in 19/20 (95%) and 20/20 (100%) subjects, respectively. IgA1 and IgG1 predominated in serum in all subjects. No subject had villous atrophy. Luminal IL-6 concentrations correlated significantly with luminal IgA2, IgM, and IgG3 concentrations but not with IgA1 or any other IgG subclass levels. Conversely, luminal IL-6 or immunoglobulin concentrations did not correlate significantly with levels of any immunoglobulin isotype in serum. These observations suggest that important relationships exist between local IL-6 and IgA2, IgM, and IgG3 responses in human small intestinal luminal secretions. Local investigation is mandatory when assessing intestinal immune activity.
Improving the gastrointestinal safety of NSAIDs: the development of misoprostol--from hypothesis to clinical practice.
University of Washington, Seattle, USA.
Arthritis is a major source of disability for the American population. It results in significant morbidity for the millions of patients affected and costs billions of dollars yearly for diagnosis and management. Nonsteroidal antiinflammatory drugs (NSAIDs) are the principal therapy for the majority of arthritis patients. It has been estimated that more than 15 million people with arthritis take these drugs daily. This use is predicted to increase greatly not only as a result of an aging population, with the consequent increase in the prevalence of arthritis, but also because NSAIDs may prove to have a role in decreasing colonic neoplasia and in reducing the likelihood of conditions such as Alzheimer's disease. It is therefore increasingly important to understand the nature of the side effects associated with these agents as well as ways of decreasing or preventing their occurrence. NSAIDs inhibit the enzymes cyclooxygenase-1 and cyclooxygenase-2. This reduces the synthesis of prostaglandins and therefore decreases joint inflammation, but it may also lead to the development of gastric and duodenal ulcers. For this reason, exogenous prostaglandins have been studied for their potential role in preventing NSAID-associated ulcers and ulcer complications. This paper reviews the development of the prostaglandin E1 analog misoprostol, the theory behind its use as a mucosal protective agent, and the results of studies in animals as well as in normal volunteers and patients with arthritis. Ultimately, a study was performed to evaluate whether misoprostol reduces the incidence of serious ulcer complications in patients taking NSAIDs. It is an interesting story, which promises to be of increasing importance as NSAID use expands to new indications while concern remains about their associated complications, especially those related to the gastrointestinal tract.
Effect of one-month treatment with nonsteroidal antiinflammatory drugs (NSAIDs) on gastric pH of rheumatoid arthritis patients.
Savarino V. Mela GS. Zentilin P. Cimmino MA. Parisi M. Mele MR. Pivari M. Bisso G. Celle G.
Dipartimento di Medicina Interna, Cattedra di Gastroenterologia and Reumatologia, Universita di Genova, Italy.
The use of NSAIDs is strongly associated with peptic ulceration. The inhibition of prostaglandin synthesis with the consequent increase of gastric acidity is considered a possible mechanism. Therefore we decided to assess the effect of one-month treatment with NSAIDs on the circadian gastric pH of rheumatoid arthritis (RA) patients. We studied 11 consecutive patients (one man and 10 women, median age 55, range 26-72 years) with confirmed RA. None was H. pylori positive. A 24-hr gastric pH recording was performed both in basal conditions and after one-month treatment with either indomethacin 150 mg/day (eight cases) or ketoprofen 300 mg/day (three cases). Only the 10 female patients were eligible for final analysis, and six matched healthy subjects not taking NSAIDs were used as control group. The number of 24-hr pH readings for various pH thresholds was calculated for both populations. The highest acid levels (pH < 3.0) did not differ between the two pH profiles of the control group (7440 vs 7391, P = NS), while they predominated after the one-month NSAID treatment (10,339 vs 11,440, P < 0.001) in RA patients. These findings show that there is an increased gastric acidity after one-month of treatment with NSAIDs in female patients with RA of recent onset. This may sustain the rationale of using antisecretory agents to prevent gastroduodenal ulcerations in these patients.
One-week triple therapy with lansoprazole, clarithromycin, and metronidazole to cure Helicobacter pylori infection in peptic ulcer disease in Korea.
Perng CL. Kim JG. El-Zimaity HM. Osato MS. Graham DY.
Department of Medicine, Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas 77030, USA.
The efficacy and acceptability of classical bismuth triple therapy may be limited by poor patient compliance and adverse effects. It is widely agreed that improved, simpler, and reliable therapies are needed to cure Helicobacter pylori infection and foster patient compliance. We evaluated the efficacy and side effects of a Bazzoli triple therapy substituting lansoprazole for omeprazole for H. pylori infection in active peptic ulcer in Korea (30 mg of lansoprazole, 250 mg of clarithromycin, and 400 mg of metronidazole, all twice daily). H. pylori status was evaluated by rapid urease test, histology, and culture at entry and four or more weeks after ending antimicrobial therapy. Fifty-eight patients (mean age: 43 years) with gastric (N = 30) or duodenal ulcer (N = 28) and H. pylori infection were studied. H. pylori was cured in 47 (81%, 95% CI = 69-90%). Mild side effects, including vomiting, diarrhea, and itching, were observed in four patients (7%). Compliance averaged 95%. Fifty-five ulcers (95%) were healed. Pretreatment pylorobulbar deformity was observed in 49 patients (85%), and in 43 (88%) the deformity disappeared after treatment. Pretreatment metronidazole and clarithromycin resistance was observed in 87% and 2% of patients, respectively. The cure rate of H. pylori infection was significantly higher in patients >50 years of age than those
Flow cytometric method to detect lymphocyte transformation in drug-allergic hepatic injury.
Ikeda T. Noguchi O. Kobayashi F. Tozuka S. Tokushima K. Sakamoto S. Marumo F. Sato C.
Department of Internal Medicine, Yokosuka Kyousai Hospital, Kanagawa, Japan.
Flow cytometric methods for the analysis of incorporated bromodeoxyuridine are extremely rapid and simple. We investigated whether these methods were useful for detecting drug-allergic hepatic injury in 18 patients with drug-allergic hepatic injury, 18 healthy controls, and 9 nonallergic patients receiving drugs. Peripheral blood mononuclear cells were stimulated with drug solutions. Incorporation of bromodeoxyuridine was detected after labeling with FITC, and S-phase cells were counted by flow cytometry. Percentages of S-phase cells in drug-stimulated culture minus those in spontaneous cultures were less than 1% in both healthy controls and nonallergic patients receiving drugs. Taking 1% as the upper limit, 13 patients (72%) were judged as positive. After the in vitro addition of interleukin-2, two patients among five who had been judged as negative were judged as positive. Lymphocyte transformation test by flow cytometry may be useful in the diagnosis of drug-allergic hepatic injury.
Suspected biliary complications after laparoscopic and open cholecystectomy leading to endoscopic cholangiography: a retrospective comparison.
Gholson CF. Dungan C. Neff G. Ferguson R. Favrot D. Nandy I. Banish P. Sittig K.
Department of Medicine, Louisiana State University College of Medicine, Shreveport, USA.
To study how suspected postoperative biliary complications are influenced by surgical technique, we compared clinical profiles of 63 patients referred for ERCP after open (OC) and laparoscopic cholecystectomy (LC) over a four-year period. ERCP was not performed for postoperative pain alone and only six (9.5%) studies were normal. Referrals after LC were younger (mean 39.1 vs 53.6 years, P < 0.001) and ERCP was requested earlier (mean 71.6 vs 2360 days, P < 0.001) in the postoperative course. Choledocholithiasis (CDL) alone, the most common finding, was successfully managed with a single ERCP in 97.2% of cases. CDL after LC occurred in younger patients (35.5 vs 58.9 years, P < 0.01) who presented earlier (mean 98.6 days vs 5.1 years, P < 0.01), without biliary ductal dilatation (P < 0.01). Although CDL after LC was associated with higher ALT and bilirubin levels than after OC, the difference was not statistically significant. Cystic duct leaks (LC: six patients, OC: four patients) were typically associated with CDL after OC and 90% resolved with endoscopic therapy. Biliary ligation (four cases) was managed successfully with choledochojejunostomy. We conclude that findings at ERCP for suspected biliary obstruction or injury after OC or LC are similar and usually can be endoscopically managed. After LC, referrals currently are younger, present much earlier, and retained stones are less likely to be associated with ductal dilatation than after OC.
Similarity in gallstone formation from 900 kcal/day diets containing 16 g vs 30 g of daily fat: evidence that fat restriction is not the main culprit of cholelithiasis during rapid weight reduction.
Vezina WC. Grace DM. Hutton LC. Alfieri MH. Colby PR. Downey DB. Vanderwerf RJ. White NF. Ward RP.
Department of Nuclear Medicine, University Campus, London Health Sciences Center, Ontario, Canada.
Diets containing essentially no fat, 1-2 g fat per day, have resulted in cholesterol gallstones. Greater fat may result in less gallbladder stasis. Do gallstones form with greater fat content? We studied 272 moderately obese subjects who had normal gallbladder ultrasonograms. The 900 kcal/day liquid diets contained either 16 g fat (N = 94) or 30 g fat (N = 178) each day for 13 weeks. A second gallbladder ultrasound was performed. Sixteen of 94 (17.0%) of the 16-g fat group developed stones with a weight loss of 18 (+/- 7) kg and a body mass index (BMI) decrease of 6 (+/- 2) kg/m2. Twenty of 178 (11.2%) of the 30-g fat group developed stones (P = 0.18, no difference in stone formation) with similar weight loss of 20 (+/- 7) kg (P = 0.08) and BMI decrease of 7 (+/- 2) kg/m2 (P = 0.04). Substantial fat for rapid weight-reducing diets resulted in gallstone formation. Since experiments have shown that our higher fat diet, containing 10 g fat per meal, results in maximal gallbladder emptying, cholelithiasis from rapid weight loss may not be solely attributable to gallbladder stasis.
Postprandial cholecystokinin response in patients with chronic pancreatitis in treatment with oral substitutive pancreatic enzymes.
Garces MC. Gomez-Cerezo J. Codoceo R. Grande C. Barbado J. Vazquez JJ.
Department of Internal Medicine, La Paz Hospital, Autonoma University of Madrid, Spain.
Cholecystokinin (CCK) response to a test meal should be increased in patients with pancreatic insufficiency, as trypsin is absent from the duodenum. If pancreatic enzymes are added, a restoration of the inhibitory feedback should result in lower levels of CCK. Ten patients with chronic pancreatitis and steatorrhea were studied. CCK basal and postprandial levels were evaluated the day before and 45 and 90 days after treatment with oral pancreatin. Twelve healthy volunteers were included as reference group. CCK basal levels did not vary. CCK response to a test meal was increased in patients before treatment and diminished when oral enzymes were maintained for months even after three days of therapy withdrawal. We conclude that long-term therapy with oral enzymes induces changes in CCK response that do not regress after three days of treatment suspension.
Overexpression of platelet-derived growth factor (PDGF) B chain and type beta PDGF receptor in human chronic pancreatitis.
Ebert M. Kasper HU. Hernberg S. Friess H. Buchler MW. Roessner A. Korc M. Malfertheiner P.
Department of Gastroenterology, Otto-von-Guericke University Magdeburg, Germany.
Platelet-derived growth factors (PDGF) are mitogenic polypeptides that are involved in cellular proliferation and tissue repair. The expression of PDGFs and type beta PDGF receptor was examined in the normal human pancreas and in chronic pancreatitis, a fibrotic disease associated with fibroblastic proliferation, atrophy, and acinar cell dedifferentiation. In the normal human pancreas, PDGF A chain mRNA levels were relatively abundant, whereas PDGF B chain mRNA levels were not detected, and type beta PDGF receptor mRNA transcripts were present at low levels. In the normal pancreas, PDGF immunoreactivity was present in islet cells, whereas type beta PDGF receptor immunoreactivity was present in acinar cells. In chronic pancreatitis, PDGF A chain mRNA transcripts were also abundant, and 11 of 19 samples exhibited the PDGF B chain mRNA transcript. In addition, there was a significant increase in the mRNA levels of type beta PDGF receptor in the pancreatitis samples by comparison with the normal pancreas (P < 0.001). In chronic pancreatitis tissues, PDGF and type beta PDGF receptor immunoreactivity were present in acinar, ductal, islet, and endothelial cells, fibroblasts, and leukocytes. The concomitant overexpression of PDGFs and of the type beta PDGF receptor points to the existence of autocrine and paracrine PDGF-dependent loops in human chronic pancreatitis.
Fecal lysozyme in assessment of disease activity in inflammatory bowel disease.
van der Sluys Veer A. Brouwer J. Biemond I. Bohbouth GE. Verspaget HW. Lamers CB.
Department of Gastroenterology and Hepatology, Leiden University Hospital, The Netherlands.
This study was undertaken to determine whether measurement of fecal lysozyme is helpful in determining disease activity in inflammatory bowel disease. In 112 patients with Crohn's disease, 46 patients with ulcerative colitis, and 40 controls, fecal lysozyme concentration was measured. Results were correlated with CDAI and AI in Crohn's disease and with Truelove and Witts' grading in ulcerative colitis. Fecal lysozyme concentration (mean +/- SEM) was significantly (P < 0.001) higher in Crohn's disease (75 +/- 14 microg/g) and ulcerative colitis (238 +/- 33 microg/g) than in controls (6 +/- 1 microg/g). There was only a weak correlation between fecal lysozyme concentration and CDAI (r = 0.32; P = 0.001) and AI (r = 0.38; P < 0.0005) in patients with Crohn's disease and with Truelove and Witts' grading (r = 0.47; P = 0.001) in ulcerative colitis. When CDAI > or = 150 or AI > or = 100 were used as the standard for active disease, fecal lysozyme concentration was elevated in 78% of patients with active colonic Crohn's disease. In ulcerative colitis fecal lysozyme concentration was increased in active disease (95% in grade II and 94% in grade III) as compared 33% in grade I. Measurement of fecal lysozyme is of little help in diagnosing and determining disease activity of inflammatory bowel disease as whole, but it may be of help for diagnosis and assessment of activity of colonic IBD.
Expression of E-selectin, sialyl Lewis X, and macrophage inflammatory protein-1alpha by colonic epithelial cells in ulcerative colitis.
Vainer B. Nielsen OH. Horn T.
Department of Gastroenterology C, Herlev Hospital, Copenhagen, Denmark.
The pathogenic significance of cell adhesion molecules (CAMs) in ulcerative colitis (UC) is largely unknown. Colonic expression of E-selectin, sialyl Lewis X (sLe(x)), and macrophage inflammatory protein-1x (MIP-1alpha) as well as serum concentrations of E-selectin and MIP-1alpha in UC were studied. Thirty patients with UC, 10 patients with irritable bowel syndrome, and 10 healthy subjects were included. Colonic biopsies were stained immunohistochemically, and blood concentrations were measured with an ELISA technique. Soluble E-selectin did not correlate with diagnosis or disease activity. MIP-1alpha was below the detection limit. Epithelial cells expressed all three molecules, both on surface membranes and intracellularly. sLe(x) staining was weaker (P = 0.0002) and MIP-1alpha staining stronger (P = 0.014) in UC patients than in controls. Leukocyte MIP-alpha staining correlated with diagnosis (P = 0.021), sLe(x) staining (P = 0.023), and colonoscopy (P = 0.018). It is shown that E-selectin, sLe(x), and MIP-1alpha are synthesized and expressed by epithelial cells, indicating that CAMs are not only involved in leukocyte extravasation and migration, but also in the interaction between leukocytes and colonic epithelium. This knowledge might contribute to the development of improved treatments in UC.
Ketotifen therapy for acute ulcerative colitis in children: a pilot study.
Jones NL. Roifman CM. Griffiths AM. Sherman P.
Division of Gastroenterology, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.
Eosinophils contribute to the inflammatory process in a variety of chronic inflammatory bowel diseases. Ketotifen is beneficial in experimental models of colitis and in patients with eosinophilic gastroenteritis. Therefore, we investigated the efficacy of ketotifen therapy for the treatment of active ulcerative colitis. Children with newly or previously diagnosed ulcerative colitis with mild-moderate disease activity were treated with ketotifen at a dosage of 4 mg daily for eight weeks. Efficacy was determined by a physician disease severity index and by endoscopic and histologic examinations. Ten patients were enrolled. Symptoms improved in four patients and resolved completely in one patient. There was endoscopic improvement in three patients and histologic improvement in one. Increased eosinophils on rectal biopsy at entry were present in two of the responders. Five patients withdrew due to a lack of symptomatic improvement. No adverse events were identified. Low-dose ketotifen offers a limited therapeutic advantage in active ulcerative colitis that may be enhanced in the subgroup of patients with a high eosinophil count in the colonic mucosa. Further study of therapeutic efficacy with increased dosages of the mast cell stabilizer for acute and maintenance therapy is warranted.
Human defunctionalized colon: a histopathological and pharmacological study of muscularis propria in resection specimens.
Violi V. Cobianchi F. Adami M. Torri T. Ferraro G. Roncoroni L.
Istituto di Clinica Chirurgica Generale e Terapia Chirurgica, University of Parma Medical School, Italy.
Despite the regression of "diversion colitis," temporary functional disorders after bowel continuity restoration could be caused by changes in the smooth muscle of excluded segments; however, studies on the muscularis propria have yielded contradictory results. This study was aimed at evaluating possible histopathological changes in muscular layers and motility of the defunctionalized human colon. Ten patients with defunctionalized colorectum (group A) and 10 controls (group B) underwent restorative or primary resection surgery. Strips were taken proximal to the colostomy (specimens A1) and the defunctionalized segment (specimens A2), and from the proximal (specimens B1) and distal extremity (specimens B2) of resected colons. Measurements of the thickness of the muscularis propria and of the volume density of the myenteric plexus, as well as of spontaneous motility and responses to electrical and pharmacological stimulation were taken. The muscularis propria was thicker in A2 than in A1 specimens (P = 0.004) and in B2 than in B1 specimens (P = 0.007). No differences were recorded either in the myenteric plexus volume density or in colonic motility. No differences were recorded in intergroup comparisons. As no structural or functional changes related to defunctionalization were found, clinical disorders after colorectal restoration could rather result from underlying colonic pathology and/or incomplete distal colon resection.
Intra- and extracellular water dynamics on rehydration in cholera and noncholera patients.
Hossain MI. Kabir I. Fuchs GJ. McCutcheon MJ. Alvarez JO. Khaled MA.
International Centre for Diarrheal Disease Research, Bangladesh, Dhaka.
To estimate the intra- and extracellular body water compartments during rehydration of patients with cholera and noncholera diarrhea by bioimpedance analyzer, we studied 30 patients with acute watery diarrhea. Total body water (TBW), intracellular water (ICW), and extracellular water (ECW) of severely dehydrated adult patients were measured with a dual frequency bioimpedance analyzer at different phases of rehydration. Fluid compartments between cholera and noncholera patients were compared. Cholera patients gained more TBW than noncholera patients during recovery. Unlike patients with noncholera diarrhea, the gain in cholera patients was mainly contributed by the ICW (1.5 +/- 1.6 vs 3.0 +/- 1.2 liters, respectively, P < 0.01). It was also observed that the recovery of the ICW compartment in cholera patients occurred rapidly within the first 2 hr after infusion. Differential dynamics of body water compartments in cholera compared to noncholera patients as observed in this study may contribute further to understanding the mechanism of dehydration in diarrheal disease, which might help in improving case management.
Plasma cholecystokinin and gallbladder responses to increasing doses of bombesin in celiac disease.
Thimister PW. Hopman WP. Rosenbusch G. Jansen JB.
Department of Gastroenterology & Hepatology, University Hospital Nijmegen, The Netherlands.
Impaired postprandial gallbladder emptying in celiac disease has been attributed to an absence of appropriate cholecystokinin release. To determine if a flat jejunal mucosa in celiac patients is related to a reduced cholecystokinin-secreting capacity, increasing doses of bombesin were infused into six patients with celiac disease and a flat jejunal mucosa (group A), in seven celiac patients with a normal jejunal mucosa while on a gluten-free diet (group B), and in seven healthy controls (group C). Bombesin induced significant (P < 0.05) increments of plasma CCK to a maximum value of 1.0 +/- 0.3 pM in group A, to 1.5 +/- 0.3 pM in group B, and to 1.2 +/- 0.3 pM in group C (NS between groups), that were accompanied by significant (P < 0.05) gallbladder emptying responses of 70 +/- 4% in group A, 47 +/- 10% in group B and 65 +/- 5% in group C. Dose-response relationships were not different between groups. We conclude that there is no major impairment of gallbladder responsiveness to bombesin or of cholecystokinin-secreting capacity in patients with a flat jejunal mucosa due to celiac disease.
Sideropenic anemia and celiac disease: one study, two points of view.
Carroccio A. Iannitto E. Cavataio F. Montalto G. Tumminello M. Campagna P. Lipari MG. Notarbartolo A. Iacono G.
Cattedra di Medicina Interna, Universita de Palermo, Italy.
Recent studies have pointed to the relationship between iron deficiency anemia and celiac disease, although data on the prevalence of celiac disease in anemic patients have been conflicting, and there is no agreement on the best screening procedure for CD in these patients. Our aims were to evaluate the relationship between anemia and celiac disease (CD) from two different points of view--the hematology clinic and the pediatric gastroenterology department--and to evaluate the utility of anti-endomysial antibody determination in screening anemic patients for CD using human umbilical cord as substrate. We studied 130 patients with CD (58 males, 72 females; median age 18 months) diagnosed at a department of Pediatric Gastroenterology, and 85 patients with iron deficiency anemia (38 males, 47 females; median age 48 years) observed at a hematology outpatient clinic. From the 85 adult patients with iron deficiency anemia, we selected a subgroup of 25 subjects with no improvement in Hb after two months of iron therapy (80 mg/day orally). Routine hematochemical tests were performed in all 215 patients. All pediatric and adult subjects underwent immunological screening for celiac disease (AGA and EmA assay); intestinal biopsy was also performed on patients testing positive. In the adult anemic patients a serum sample was stored at -20 degrees C on first observation, and after 6-18 months EmA on human umbilical cord were assayed. In the pediatric patients with CD, anemia was observed in 91/130 patients (70% of cases, the most frequent symptom after poor growth); however, this was the only presenting symptom of CD in 2/130 patients (1.5% of cases). Anemia was sideropenic in 41/91 patients (iron
Small intestinal transit time and intraluminal pH in ileocecal resected patients with Crohns disease.
Fallingborg J. Pedersen P. Jacobsen BA.
Department of Medical Gastroenterology, Aalborg Hospital, Denmark.
The pH and transit times of the gut are important for the delivery of active drug from several tablets used in the treatment of Crohn's disease (CD). Many patients with CD undergo an ileocecal resection, which might influence small intestinal pH and transit time. The effect of ileocecal resection on these variables has not previously been studied. Intraluminal pH and transit time were measured in nine ileocecal-resected CD patients and 13 healthy volunteers using pH-sensitive radiocapsules. Small intestinal transit time (SITT) was significantly shorter in ileocecal-resected patients (5.2 hr, controls 8.0 hr). The pH levels of the small intestine were identical in patients and controls, whereas cecal pH was 0.9 pH units higher in resected CD patients. The time spent with pH higher than 5.5, 6.0, 6.5, and 7.0 was significantly shorter in patients than in controls. There was no correlation between the SITT and the length of resected ileum or between the SITT and the time elapsed since the resection. We conclude that ileocecal resection decreases the SITT and the time with pH higher than 5.5-7.0. The study indicates that this reduction of the SITT is mainly due to the resection of the ileocecal valve and is, to a certain extent, independent of the length of resected ileum. An ileocecal resection might therefore affect the delivery of active drug from tablets with pH-dependent delivery.
IL-10 synergizes with IL-4 and IL-13 in inhibiting lysosomal enzyme secretion by human monocytes and lamina propria mononuclear cells from patients with inflammatory bowel disease.
Lugering N. Kucharzik T. Stein H. Winde G. Lugering A. Hasilik A. Domschke W. Stoll R.
Department of Medicine B, University of Munster, Germany.
Tissue injury and inflammation in inflammatory bowel disease (IBD) are associated with enhanced monocytic lysosomal enzyme release. In this study, peripheral monocytes and lamina propria mononuclear cells (LPMNC) were isolated from IBD patients and normal controls. Cells were stimulated with lipopolysaccharide after treatment with IL-13, IL-4, and IL-10, and enzyme secretion was assessed by using the corresponding p-nitrophenyl glycosides as substrates. Molecular forms of cathepsin D were examined to describe the mode of enzyme release. IL-10 and IL-4 strongly down-regulate enzyme secretion in IBD monocytes. IBD monocytes showed a diminished responsiveness to the inhibitory effect of IL-13. Impaired monocyte response was not found with combinations of IL-13 and IL-10 or IL-4 and IL-10. LPMNC from involved IBD mucosa showed significantly higher enzyme secretion compared with LPMNC from noninvolved IBD mucosa but responded inefficiently to either IL-4, IL-13, or IL-10 alone. However, combined treatment with IL-10 and IL-4 or IL-10 and IL-13 strongly suppressed enzyme release by these cells. Both the precursor and mature forms of cathepsin D were elevated in IBD patients. While IL-13 reduced mainly the precursor form, the effect of IL-4 and IL-10 concerns both the precursor and mature form of cathepsin D. Our results favor the potent clinical utility of combined treatment, thus improving chances of developing effective treatments for human IBD.
Polymorphism of motilin gene in patients with Crohns disease.
Annese V. Piepoli A. Andriulli A. Napolitano G. Bisceglia L. Zelante L. Gasparini P.
Division of Gastroenterology, C.S.S. Hospital, I.R.C.C.S., San Giovanni Rotondo, Italy.
An increasing body of evidence supports the concept of genetic heterogeneity within inflammatory bowel disease (IBD). In this study, a polymorphism of the motilin gene, which determines an amino acid substitution in the motilin protein, has been investigated in IBD patients. Fifty patients with ulcerative colitis (UC), and 52 with Crohn's disease (CD) were investigated for anti-neutrophil cytoplasmatic antibodies (ANCA) and the polymorphism in the second exon of the motilin gene. Sixty unrelated blood donors served as controls. ANCA were found in 30% of UC and 13% of CD. In controls the DNA polymorphism identified two alleles (1 and 2) at a frequency of 42% and 58%, respectively. Patients with either UC or CD showed a slight increase in the frequency of allele 2 (69% and 60%, respectively; P > 0.05 vs controls). This allele was predominant in ANCA-positive CD patients (86%; P < 0.04) while in UC it did not differ. All ANCA-positive CD patients had the disease confined to the colon. A polymorphism of second exon of the motilin gene, leading to a protein variant, is significantly more frequent in the subset of ANCA-positive CD patients. This subgroup of patients appears to share peculiar genetic and clinical features.
Increased prevalence of autoantibodies in celiac disease.
Lerner A. Blank M. Lahat N. Shoenfeld Y.
Department of Pediatrics, Carmel Medical Center, Haifa, Israel.
Several features suggest an immune mechanism operates in celiac disease. Information on the autoantibody repertoire in this condition is lacking. The purpose of the study was to investigate the reactivity of celiac patients sera to various autoantigens widely distributed in the human intestine. Seventy children, celiacs and controls, were evaluated for serum autoantibodies using ELISA and immunofluorescence. Celiac patients had increased prevalence of serum anti-single-stranded DNA (14%), anti-double-stranded DNA (23%), anti-cardiolipin (14%), and anti-endomysial autoantibodies (63%). The relevance of this finding on the extraintestinal manifestations of celiac disease or the coexistence of autoimmune conditions and celiac disease remains to be determined.
Asymptomatic Helicobacter pylori gastritis is associated with increased sucrose permeability.
Borch K. Sjostedt C. Hannestad U. Soderholm JD. Franzen L. Mardh S.
Department of Surgery, University Hospital of Linkoping, Sweden.
Our aim was to investigate whether there are changes in permeability to sucrose in asymptomatic Helicobacter pylori gastritis. Nineteen asymptomatic subjects with Helicobacter pylori-associated gastritis with no or mild mucosal atrophy and 19 age- and sex-matched normal controls were studied by peroral load of sucrose (100 g). The fraction of the given oral dose of sucrose excreted in urine was increased in subjects with Helicobacter pylori gastritis (median 0.08% versus 0.04% in controls). Sucrose excretion was not related to atrophy, intestinal metaplasia, or inflammation in the gastric mucosa. However, sucrose permeability was related to the degree of inflammatory (neutrophil) activity, since moderate activity was associated with higher sucrose excretion than mild activity (median 0.13% vs 0.07%). Asymptomatic Helicobacter pylori gastritis was associated with an increased sucrose permeability, which could be a sign of gastric mucosal leakage. This could have implications for the diseases and complications associated with Helicobacter pylori infection.
Low prevalence of Helicobacter pylori infection in patients with hamartomatous fundic polyps.
Sakai N. Tatsuta M. Hirasawa R. Iishi H. Baba M. Yokota Y. Ikeda F.
Department of Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan.
Helicobacter pylori infection of the gastric mucosal surface was investigated in patients with hamartomatous fundic polyps or hyperplastic polyps and in patients without endoscopic evidence of disease (healthy subjects). Presence of H. pylori infection was determined by culture, histologic examination, and the endoscopic phenol red test. Adherence of H. pylori was evaluated with scanning electron microscopic examination of antral biopsy specimens. Both prevalence of H. pylori infection (P < 0.001) and H. pylori adherence (P < 0.05) were less in patients with hamartomatous fundic polyps than in healthy subjects and patients with hyperplastic polyps. However, the percentages of plasma cells in gastric mucosa that contained IgA and of gastric epithelial cells that expressed Lewis b did not differ significantly among the three groups. These findings suggest that defense mechanisms against the attachment of H. pylori other than IgA or Lewis b antigen are present in patients with hamartomarous fundic polyps.
Double-blind comparison of lansoprazole 15 mg, lansoprazole 30 mg, and placebo in the maintenance of healed gastric ulcer.
Kovacs TO. Campbell D. Haber M. Rose P. Jennings DE. Richter J.
Center for Ulcer Research and Education, VA Medical Center West Los Angeles, California 90073, USA.
Our purpose was to compare the safety and efficacy of lansoprazole 15 mg and 30 mg with placebo in preventing recurrence in 49 patients with a history of gastric ulcer. Within one month, 40% of patients receiving placebo experienced ulcer recurrence compared to 0% and 7% of patients receiving lansoprazole 15 mg and 30 mg, respectively. All placebo patients became symptomatic, experienced ulcer recurrence or withdrew from the study by month 9. As compared to placebo, a significantly (P < 0.001) higher percentage of patients treated with lansoprazole 15 mg (83%) and lansoprazole 30 mg (93%) with healed gastric ulcer disease remained healed at month 12. Of patients asymptomatic at baseline, 100% and 59% of those treated with lansoprazole 15 mg and 30 mg, respectively, remained asymptomatic at month 12. The incidence of adverse events was comparable among the treatment groups. Lansoprazole safely and effectively reduces ulcer recurrence in patients with a history of gastric ulcer disease.
Impact of ingested liquids on 24-hour ambulatory pH tests.
Shoenut JP. Duerksen D. Yaffe CS.
St. Boniface General Hospital, and Department of Medicine, University of Manitoba, Winnipeg, Canada.
A prospective investigation of the impact of ingested liquids on 24-hr pH test scores was conducted. Eighty-two patients contributed 142 samples. The liquids used were coffee/tea (N = 35), water (N = 32), fruit juice (N = 29), cola (N = 34), and beer (N = 12). The pH of cola, juice, and beer are approximately 3.0. The parameters studied included: total test time, total drink time, total minutes of pH < 4.0 during drink, minutes of < pH 4.0 10 min before drink, and minutes of pH < 4.0 10 min following drink. Analysis was performed using one-way ANOVA and repeated measures. Age of patients, total test time, and total time pH < 4.0 were not significantly different (P > 0.05). The total time to consume the drink was significantly greater (P < 0.05) for beer than all other liquids. The total time (7.7 +/- 6.0 min) pH < 4.0 for cola was significantly different (P < 0.023) than beer (3.3 +/- 3.7 min), tea/coffee (1.4 +/- 6.5 min), and water (1.1 +/- 2.5 min). The percentage of total time pH < 4.0 was not significantly different (P > 0.05) among any of the liquids. The percentage of time pH < 4.0 during the drink was the highest for cola (63 +/- 47%) and juice (51 +/- 57%); water, coffee/tea, and beer were not significantly different (P > 0.05). Although the impact of cola and juice were the greatest, none of these had an impact that exceeded 0.5%. The lack of impact of beer appears to be due to the increased period of time it takes to consume. We conclude that the impact of ingested fluids is minimal and can probably be disregarded in most patient groups.
Effect of amino acids on lower esophageal sphincter characteristics and gastroesophageal reflux in humans.
Gielkens HA. Lamers CB. Masclee AA.
Department of Gastroenterology-Hepatology, University Hospital Leiden, The Netherlands.
The effect of a commercially available mixed amino acids solution, when given either intravenously or intragastrically, on lower esophageal sphincter (LES) pressure, frequency of transient LES relaxations (TLESRs) and gastroesophageal reflux (GER) was investigated in six healthy volunteers. LES pressure and esophageal pH were simultaneously recorded on three separate occasions 1 hr before (basal) and 3 hr during intravenous or intragastric infusion of amino acids (250 mg protein/kg/hr) or saline (control). No significant changes in LES pressure were seen in the control experiment. Intravenous amino acids caused a rapid and sustained (P < 0.01) decrease in LES pressure whereas intragastric amino acids decreased LES pressure only gradually and temporarily (P < 0.01). In the three experiments no significant differences were observed in TLESR frequency, the number of GER episodes, the mechanism of reflux, or duration of acid exposure. In healthy subjects both intragastric and, especially, intravenous infusion of amino acids significantly decrease LES pressure but do not affect the frequency of TLESRs or GER episodes during a continuous liquid gastric load.
Concurrent fluoroscopy and manometry reveal differences in laparoscopic Nissen and anterior fundoplication.
Anderson JA. Myers JC. Watson DI. Gabb M. Mathew G. Jamieson GG.
University Department of Surgery, Royal Adelaide Hospital, South Australia.
A prospective double-blind randomized trial was initiated to examine two types of laparoscopic fundoplication (Nissen and anterior). Thirty-two patients with proven gastroesophageal reflux disease presenting for primary laparoscopic antireflux surgery were randomized to undergo either Nissen fundoplication (N = 13) or anterior hemifundoplication (N = 19). Postoperative fluoroscopic and manometric examination was carried out concomitantly. Nissen fundoplication resulted in significantly greater elevation of resting (33.5 vs 23 mm Hg) and residual lower esophageal sphincter pressures (17 vs 6.5 mm Hg) and lower esophageal ramp pressure (26 vs 20.5 mm Hg) than the anterior partial fundoplication. A smaller radiologically measured sphincter opening diameter was seen following Nissen fundoplication (9 mm) compared with anterior fundoplication (12 mm). Lower esophageal ramp pressure correlated weakly (r = 0.37, P = 0.04) with postoperative dysphagia. It is concluded that the type of fundoplication performed significantly influences postoperative manometric and video barium radiology outcomes. The clinical relevance of this requires further investigation.
Most Helicobacter pylori-infected patients have specific antibodies, and some also have H. pylori antigens and genomic material in bile: is it a risk factor for gallstone formation?
Figura N. Cetta F. Angelico M. Montalto G. Cetta D. Pacenti L. Vindigni C. Vaira D. Festuccia F. De Santis A. Rattan G. Giannace R. Campagna S. Gennari C.
Institute of Internal Medicine, University of Siena, Italy.
Bile may contain a 130-kDa protein endowed with aminopeptidase activity and the ability to promote cholesterol crystallisation. As >90% of H. pylori strains have a similar peptidase activity, and half the isolates express a 110- to 140-kDa antigen, the CagA protein, we investigated a possible association between H. pylori infection and gallstones, and the presence in bile samples of factors related to H. pylori that could increase cholesterol crystallization. The prevalence of H. pylori infection was 82.1% in 112 patients with gallstones and 80.3% in 112 controls (NS). Fifteen bile samples out of 23 specimens from infected patients (65.2%) contained anti-CagA antibodies. A approximately 60-kDa antigen only reacting with an anti-CagA antibody was found in five bile samples (21.7%) from 23 infected patients. One bile sample (4.1%) contained ureA and cagA genes of H. pylori. The homology of CagA with the N-terminal sequence of aminopeptidase N was very low. We concluded that the presence of specific antibody to H. pylori in most bile samples tested and of an H. pylori putative antigen in a discrete number of cases may represent factors that increase the risk of gallstone formation.
Analysis of human T-cell antigen receptor variable beta gene usage following vaccination with recombinant HBsAg.
Yuh K. Sugyo S. Nakamura K. Shijo H. Emi K. Harada K. Yoshitake S. Kimura N. Moribe T. Kaneshige T. Okumura M.
First Department of Internal Medicine, School of Medicine, Fukuoka University, Japan.
We analyzed the TcR Vbeta gene usage before and after vaccination with the hepatitis B vaccine since changes in the TcR Vbeta gene families would be considered to provide preliminary evidence of a mechanism to prevent HBV infection. Six healthy adult volunteers received immunizations. TcR Vbeta usage, T-cell proliferation, and HLA class II alleles were examined in peripheral blood mononuclear cells (PBMC) both before and after vaccination. Furthermore, TcR Vbeta usage in postimmunization PBMC was also compared with PBMC cultured with recombinant HBsAg (rHBsAg). The level of in vitro T-cell proliferation in the presence of rHBsAg increased significantly (P < 0.01) in PBMC isolated after vaccinations. Increases in the different TcR Vbeta genes were also observed in each individual following vaccinations, regardless of the similarity in their HLA alleles. Specific HBV-related antigen-responsive T cells were induced after HB vaccination, without any common restriction for the TcR Vbeta gene families. The mechanism that helps prevent HBV infection was thus found to involve multiclonal alterations in the TcR Vbeta repertoire.
Chronic splanchnic hemodynamic effects of spironolactone with unrestricted sodium diet in patients with compensated cirrhosis.
Sugano S. Kawafune T. Okajima T. Ishii K. Watanabe M. Takamura N.
Department of Internal Medicine, Saiseikai Wakakusa Hospital, Yokohama, Japan.
The purpose of this study is to determine the hemodynamic effects of spironolactone administration associated with an unrestricted sodium diet (salt 10 g) in patients with compensated cirrhosis and portal hypertension. We studied the hemodynamic changes following eight weeks of administration of either placebo (N = 6) or spironolactone (100 mg/day) (N = 6 Pugh-Child's A and 6 B). No significant changes were observed after the administration of the placebo. Spironolactone induced a significant reduction in the hepatic venous pressure gradient (HVPG) (-10.1 +/- 13.3%, P < 0.05), which was associated with a significant reduction of cardiac output (-11.5 +/- 9.3%, P < 0.01), plasma volume (-8.1 +/- 4.7%, P < 0.01), and wedged hepatic venous pressure (-10.5 +/- 11.6%, P < 0.05). There was no significant change in hepatic blood flow and there was no significant correlation between the change in the HVPG and the change in circulating plasma volume. A decrease in the HVPG greater than 10% was observed in eight of 12 patients (67%), defined as responders, at eight weeks. Six of six (100%) grade A patients and two of six (33%) grade B patients responded. This study demonstrated that spironolactone with an unrestricted sodium diet decreased the HVPG in grade A patients but did not significantly decrease the HVPG in grade B patients.
Giant gastric ulcers and risk factors for gastroduodenal mucosal disease in orthotopic lung transplant patients.
Lipson DA. Berlin JA. Palevsky HI. Kotloff RM. Tino G. Bavaria J. Kaiser L. Long WB. Metz DC. Lichtenstein GR.
Department of Internal Medicine, University of Pennsylvania Medical Center, Philadelphia, USA.
Giant gastric ulcers are defined as ulcers with a diameter greater than 3 cm. Previously they have not been described in lung transplant recipients. We report a high incidence of symptomatic giant gastric ulcers and identify the risk factors for ulcer development in these patients. We examined the records of all 95 patients who had undergone lung transplantation at our institution from November 1991 to July 1995. Fourteen of the patients who underwent lung transplantation developed symptoms that required esophagogastroduodenoscopy. Three of these patients (21%) were found to have giant gastric ulcers. The relative risk of giant gastric ulcer in symptomatic patients undergoing endoscopy after lung transplantation is over 40 times that of population controls. The patients who developed giant gastric ulcers, despite H2 antagonist use, had all received bilateral lung transplantation and had received nonsteroidal antiinflammatory drugs, cyclosporine, and high-dose intravenous corticosteroids. The risk of developing giant gastric ulcers is significantly increased in patients who have undergone bilateral orthotopic lung transplantation. Clinicians should be made aware of this complication in order to avoid use of ulcerogenic medications in this population. Avoidance of these medications could potentially minimize the risk of this complication.
Helicobacter pylori infection and peptic ulcer disease in cirrhosis.
Department of Internal Medicine, Chi Mei Foundation Hospital, Yung Kang City, Tainan, Taiwan.
An increased frequency of peptic ulcer disease is noted in patients with cirrhosis, but the role of H. pylori in this disorder remains to be determined. The diagnosis of cirrhosis was confirmed by a combination of clinical, biochemical, radiological, and histological methods. The severity of cirrhosis was assessed by Pugh's modification of Child's criteria. Upper gastrointestinal endoscopy was performed consecutively to evaluate the presence of varices and gastroduodenal mucosa. H. pylori status was assessed by histology, urease test, and serology. In all, 130 patients with cirrhosis were recruited into the study; there were 86 males and 44 females with a mean (SD) age of 54.4 (12.7) years. The H. pylori prevalence was 76.2%. There was no difference in age between the H. pylori-positive and -negative cirrhotics (P = 0.29). The H. pylori prevalence revealed no difference among cirrhotics with Child A (77.8%), Child B (72.9%), and Child C (78.6%) (P = 0.8), and neither was there a difference in H. pylori prevalence in cirrhotics with and without congestive gastropathy (77% vs 73.7%, P = 0.84). The prevalence of H. pylori in cirrhotics with and without varices did not show a statistical difference (75% vs 81.8%, P = 0.68). There also was no difference in the H. pylori prevalence between cirrhotic patients with and without peptic ulcers (84.4% vs 69.7%, P = 0.09). In conclusion, the prevalence of H. pylori or peptic ulcer is independent of the severity of cirrhotic liver disease. The association between H. pylori infection and peptic ulcer disease is weak in cirrhosis.
In vitro wound repair by human gastric fibroblasts: implications for ulcer healing.
Piazuelo E. Lanas A. Jimenez P. Garcia-Gonzalez A. Esteva F.
Unidad Mixta de Investigacion, Service of Biochemistry, Hospital Clinico Universitario, Universidad de Zaragoza, Spain.
Fibroblasts modulate epithelial biological activities and play a key role in the ulcer healing process. There is no information regarding the biological response of human gastric fibroblasts to regulatory compounds. The aim of this study was to assess the effects of growth factors and prostaglandins on an in vitro model of human gastric fibroblast wound repair. Subconfluent fibroblast cultures were used to study proliferative responses, determined by [3H]thymidine incorporation into DNA. In vitro wound repair was determined in confluent fibroblast monolayers after mechanical denudation. The presence of putative growth factors secreted by fibroblasts was studied in conditioned medium by heparin-affinity chromatography and immunodetection with specific antibodies. Serum and platelet-derived growth factor (PDGF) -BB induced a dramatic increase in both gastric fibroblast proliferation and closure of wounded cell monolayers, whereas these activities were inhibited by both transforming growth factor (TGF) -beta1 and prostaglandin E1. Basal activities in unstimulated gastric fibroblasts were lower than those obtained in skin fibroblasts. Conditioned medium stimulated fibroblast proliferation and wound repair activity, which was inhibited by the addition of suramin, and was partially dependent on the presence of PDGF-like factor. PDGF is a major, autocrine promotor of human gastric fibroblast-dependent wound repair activities, which are inhibited by prostaglandins and TGF-beta. These findings might be important for future therapeutic ulcer healing approaches.
Gallstone prevalence in Germany: the Ulm Gallbladder Stone Study.
Kratzer W. Kachele V. Mason RA. Hill V. Hay B. Haug C. Adler G. Beckh K. Muche R.
Department of Internal Medicine, Institute for Clinical Chemistry, University of Ulm, Germany.
The Ulm Gallbladder Stone Study is the first ultrasound-based epidemiologic survey of cholecystolithiasis in the former West Germany. A study population of 1116 blood donors (656 men, age 38.0 +/- 12.0 years; 460 women, age 34.1 +/- 11.2 years) at the Central Blood Bank of the German Red Cross in Ulm was examined between April 1994 and February 1995. Based on age, subjects were assigned to one of four groups (18-30, 31-40, 41-50, and 51-65 years). Following a structured interview of each study subject, an ultrasound examination was carried out and a blood sample obtained for laboratory study. Overall, 6.0% (95% (95% CI: 4.8%-7.6%) of all study subjects (5.8% of the men and 6.3% of the women) exhibited evidence of current or past gallbladder disease (cholelithiasis or history of cholecystectomy). The prevalence of gallbladder disease correlated positively with age, reaching a maximum of 13.7% (9.5-20.0) in the 51- to 65-year-old age group, and also correlated as with body mass index (BMI). Female subjects with previous full-term pregnancies showed a higher prevalence of cholelithiasis, but this difference was not statistically significant for age-adjusted analysis. Subjects with a family history of cholelithiasis were found to suffer from gallstones in 11.5% (8.0-16.7) of cases compared with 4.6% (3.4%-6.3%) of subjects without such family history. Autopsy studies conducted in Germany have shown the prevalence of gallstones to be about 13.1% in men and 33.8% in women. Our sonographic data are relatively low in comparison. This may be due, in part, to the specific selection characteristics inherent in retrospective autopsy studies, such as age distribution and the presence of other pathologic factors associated with increased risk for cholelithiasis. The Ulm data rank in the lower third of the prevalence range reported for European sonographic studies to date. Age, positive family history, and increased BMI all correlated positively with the prevalence of gallbladder disease (P < 0.05). For the study population as a whole, there was no gender-specific increased risk for the development of gallstones.
Adjuvant cholylsarcosine during ursodeoxycholic acid treatment of primary biliary cirrhosis.
Ricci P. Hofmann AF. Hagey LR. Jorgensen RA. Rolland Dickson E. Lindor KD.
Division of Gastroenterology and Hepatology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
We postulated that coadministration of cholylsarcosine with ursodeoxycholic acid might provide additional benefit to primary biliary cirrhosis patients with an incomplete response to ursodeoxycholic acid. Our aim was to test the tolerability and the effect of adjuvant cholylsarcosine on liver tests and plasma cholesterol in primary biliary cirrhosis patients receiving ursodeoxycholic acid. Four primary biliary cirrhosis patients, who, despite more than a year of ursodeoxycholic acid therapy, had one or more liver tests persistently equal to or greater than twice the upper limit of normal, received cholylsarcosine (12-15 mg/kg/day) in addition to ursodeoxycholic acid (13-15 mg/kg/day) for six weeks in an open label study. Values of liver tests and plasma cholesterol, determined every two weeks, remained unchanged. One patient discontinued cholylsarcosine at week 4 because of new-onset pruritus. Analysis of duodenal bile acids in one patient showed 52% enrichment in cholylsarcosine and hydrophilic bile acids constituted 87% of total bile acids. It is concluded that the addition of cholylsarcosine to ursodeoxycholic acid did not influence liver tests in four primary biliary cirrhosis patients who had not responded completely to ursodeoxycholic acid alone. Cholylsarcosine was absorbed and became a dominant biliary bile acid; its administration was associated with increased pruritus.
Effects on gastric circulation of treatment for portal hypertension in cirrhosis.
Sezai S. Ito M. Sakurai Y. Kamisaka K. Abe T. Ikegami F. Yamamoto Y. Hirano M.
Division of Gastroenterology, Kanto NTT Hospital, Tokyo, Japan.
We evaluated the gastric circulatory effects of the type of treatment administered for portal hypertension. Of 14 patients with cirrhosis, seven received a transjugular intrahepatic portosystemic shunt (TIPS; group T) and seven received percutaneous transhepatic portographic embolization (PTPE; group P). Patients were evaluated over the course of one year. After treatment, portal venous pressure was significantly reduced from 39 +/- 6 cm H2O to 32 +/- 5 (P < 0.001) in group T and was significantly elevated from 29 +/- 10 to 33 +/- 8 (P < 0.05) in group P. The portal flow velocity (Vmean) was significantly higher in group T vs group P (P < 0.0001). The congestion index was significantly lower in group T than in group P (P < 0.0001). The gastric mucosal blood flow was increased in group T but was unchanged in group P. Esophageal varices showed some improvement in both groups, but the portal hypertensive gastropathy was improved only in group T. These findings help to explain the differing effects on the gastric circulation related to the type of treatment used for portal hypertension.
Hepatitis G and C viruses respond to interferon-alpha with different virologic kinetics.
Yang G. Caroli-Bosc FX. Laffont C. Bianchi D. Dantin S. Lefebvre JC. Doglio A.
Laboratoire de Virologie, Faculte de Medecine, Nice, France.
The aim of this work was to specify the time course of response to interferon (IFN) of hepatitis G virus (HGV) and hepatitis C virus (HCV) in coinfected individuals. A group of 33 patients, undergoing 12 months of IFN therapy for chronic hepatitis C, was screened for the presence of both HGV and HCV RNAs to select seven coinfected patients. Spontaneous recovery from HGV infection was excluded through the detection of antibodies to the envelope-2 protein of HGV and HCV isolates were genotyped. Within three months of treatment, we found that HGV RNA was transiently cleared in 6/7 patients, but the rate of long-term favorable response was very low (1/7). In addition, considering the same individuals separately, it was shown that HGV and HCV responded to IFN with different kinetics in 5/7 patients. Taken together, these results underscore the importance of the virological basis of the resistance to IFN treatment.
Prognostic evaluation of early indicators in fulminant hepatic failure by multivariate analysis.
Dhiman RK. Seth AK. Jain S. Chawla YK. Dilawari JB.
Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Viral hepatitis is the commonest cause of fulminant hepatic failure (FHF) in developing countries. We evaluated the early indicators of prognosis in these patients by multivariate analysis. The records of 204 consecutive patients with acute liver failure admitted with hepatic encephalopathy over five years were studied. The etiology of these patients included virus related in 186 (91.1%), drug induced in 15 (7.4%), Wilson's disease in one (0.5%), acute Budd-Chiari syndrome in one (0.5%), and malignant infiltration in one (0.5%). Patients with FHF complicating viral hepatitis were analyzed by univariate and multivariate analysis. These patients were further subclassified depending upon the interval between the onset of jaundice and the onset of encephalopathy into hyperacute (HALF; interval 0-7 days), acute (ALF; interval 8-28 days) and subacute liver failure (SALF; interval 4-12 weeks). Sixty (32.3%) patients with viral hepatitis survived. Univariate analysis showed that the interval between onset of encephalopathy and onset of jaundice, grade of encephalopathy, raised intracranial pressure, prothrombin time, and serum bilirubin levels on admission were related to outcome in these patients. Multivariate logistic regression analysis showed that the presence of raised intracranial pressure at the time of admission, prothrombin time >100 sec on admission, age (>50 yr), and onset of encephalopathy seven days after onset of jaundice were associated with poor prognosis. Forty seven (37.0%) of 129 patients with HALF survived compared with 9 (22.5%) of 40 with ALF and 4 (21.1%) of 19 with SALF (P = NS). Raised intracranial pressure was more frequent in patients with HALF (48.8%) than in patients with ALF (32.5%) and SALF (15.8%; P = 0.01), while clinically detectable ascites was more frequent in patients with SALF (78.9%) compared with HALF (19.7%) and ALF (37.5%; P < 0.0001). The factors adversely affecting the outcome in our patients with FHF complicating viral hepatitis include presence of overt clinical features of raised ICP at the time of hospitalization, prothrombin time (>100 sec) on admission, age (>50 yr), and onset of encephalopathy seven days after onset of jaundice.
Prognostic value of generation of growth hormone-stimulated insulin-like growth factor-I (IGF-I) and its binding protein-3 in patients with compensated and decompensated liver cirrhosis.
Assy N. Hochberg Z. Enat R. Baruch Y.
Department of Medicine B, The Liver Unit, Rambam Medical Center, Haifa, Israel.
Our aim was to study the prognostic value of growth hormone (GH) -stimulated insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) generation in patients with compensated [group 1 (N = 8) with a Child-Pugh (CP) score of 5-8] and decompensated postnecrotic liver cirrhosis [group 2 (N = 7) with a CP score of 9-12]. Serum levels of IGF-I, GH-binding protein (GHBP), and IGFBP-3 were measured before and 24 hr after a single subcutaneous injection of recombinant human GH (rhGH, 0.14 units/kg). Patients (mean age 56 years) were followed prospectively for three years. Six patients (40%) died during the follow-up period, of whom half had a CP score
Antibodies to Ro/La, Cenp-B, and snRNPs antigens in autoimmune hepatitis of North America versus Asia: patterns of immunofluorescence, ELISA reactivities, and HLA association.
Parveen S. Morshed SA. Arima K. Nishioka M. Czaja AJ. Chow WC. Ng HS.
Third Department of Internal Medicine, Kagawa Medical School, Japan.
To assess whether demography is one of the important factors determining antibody response to nuclear antigens [ANA: SSA-Ro (52K and 60K), SSB-La, snRNPs (A, 70K, B'/B), and Cenp-B], we investigated 95 and 47 sera of autoimmune hepatitis (AIH) from North America and Asia, respectively, by immunofluorescent (IF) and recombinant ELISA. Correlations among nuclear IF patterns, ELISA, and disease indices were analyzed. The frequency and titer of individual antibodies differed significantly between the groups. Patients with speckled patterns were younger in both regions and had higher aspartate aminotransferase levels only in North America. HLA-A1, B8, DQ2, and DR4 or DR3 or both in North America, and A2, B61, DQ7, and DR4 in Asia were predominant. In Asia, B61 correlated with anti-70K, and DQ7 correlated with antibodies to 52K, Cenp-B, and B'/B. In North America, A1, B8, DR3 haplotype, and DQ2 correlated with antibodies to A and 70K. Anti-B'/B and DR4 in North America, and A2 in Asia, were associated with concurrent immunologic disorder. Individual ANA clusters correlated with individual HLA in the demography, and different HLA alleles might determine disease expression as well as different ANA being produced in AIH.
Collagenous colitis and Yersinia enterocolitica infection.
Makinen M. Niemela S. Lehtola J. Karttunen TJ.
Department of Pathology, University of Oulu, Finland.
Collagenous colitis is a rare clinical and pathological entity characterized by watery diarrhea and deposition of collagen beneath the surface epithelium of the colon. Its etiology is unknown. We present a careful retrospective clinicopathological analysis of six patients with collagenous colitis diagnosed at our hospital during a three-year period. Three of the patients had had a Yersinia enterocolitica infection, detected by stool culture and elevated serum antibody titers, preceding the diagnosis of collagenous colitis. Four patients had duodenal villous atrophy, which in two patients was refractory to a gluten-free diet. We propose that Yersinia enterocolitica infection may be a triggering factor for the development of collagenous colitis in some cases. Duodenal villous atrophy not responding to gluten withdrawal is common in association with collagenous colitis.
Effect of leuprolide acetate in treatment of abdominal pain and nausea in premenopausal women with functional bowel disease: a double-blind, placebo-controlled, randomized study.
Mathias JR. Clench MH. Abell TL. Koch KL. Lehman G. Robinson M. Rothstein R. Snape WJ.
University of Texas Medical Branch, Galveston, USA.
We have previously reported impressive results in using a gonadotropin-releasing hormone analog, leuprolide acetate (Lupron), in the treatment of moderate to severe symptoms (especially abdominal pain and nausea) in patients with functional bowel disease (FBD). Pain is the hallmark of patients with FBD, and there is no consistent therapy for the treatment of these patients. The purpose of the present study was to expand the investigation to study similar patients (menstruating females) in a multicenter, double-blind, placebo-controlled, randomized study using Lupron Depot (which delivers a continuous dose of drug for one month), 3.75 mg (N = 32) or 7.5 mg (N = 33), or placebo (N = 35) given intramuscularly every four weeks for 16 weeks. Symptoms were assessed using daily diary cards to record abdominal pain, nausea, vomiting, early satiety, anorexia, bloating, and altered bowel habits. Additional assessment tools were quality of life questionnaires, psychological profile, oral-to-cecal transit using the hydrogen breath test, antroduodenal manometry, reproductive hormone levels, and global evaluations by both patient and investigator. Patients in both Lupron Depot-treated groups showed consistent improvement in symptoms; however, only the Lupron Depot 7.5 mg group showed a significant improvement for abdominal pain and nausea compared to placebo (P < 0.001). Patient quality of life assessments and global evaluations completed by both patient and investigators were highly significant compared to placebo (P < 0.001). All reproductive hormone levels significantly decreased for both Lupron Depot-treated groups by week 4 and were significantly different compared to placebo at week 16 (P < 0.001). This study shows that leuprolide acetate is effective in controlling the debilitating symptoms of abdominal pain and nausea in patients with FBD.
Activated protein C resistance, thrombophilia, and inflammatory bowel disease.
Heneghan MA. Cleary B. Murray M. O'Gorman TA. McCarthy CF.
Department of Medicine, Clinical Science Institute, University College Hospital Galway, Ireland.
Thromboembolic events frequently complicate the clinical course of patients with inflammatory bowel disease (IBD). Hereditary thrombophilia may contribute to this tendency. Resistance to activated protein C is the most recently described thrombophilic state and may account for up to 40% of patients with thrombophilia. Thirty-seven patients with IBD were studied (mean age 44 years, range 18-82 years). Three patients had a history of thrombotic episodes. The 37 controls included 23 men and 17 women (mean age 48 years, range 16-89 years). Disease activity was assessed using the Harvey Bradshaw index for patients with Crohn's disease and the Truelove and Witts grading system for patients with ulcerative colitis. Levels of fibrinogen, antithrombin III (ATIII), protein C, protein S, activated protein C resistance (APCR), and the presence of a lupus anticoagulant (LA) were determined. Median ATIII levels in patients with IBD were significantly lower than controls (98% vs 106%, P = 0.007), while fibrinogen was elevated (4.2 vs 3.3 g/liter, P = 0.026) despite quiescent disease activity. LA was detected in 7/37 patients in the IBD group compared to 0/37 controls. (chi2 = 5.68, P = 0.017). No significant difference was observed in levels of inherited thrombophilic factors and in particular APCR between IBD patients and controls. In conclusion, the presence of inherited thrombophilic defects, in particular APCR, is uncommon in patients with IBD and does not merit routine screening.
Interferon-alpha2b therapy is efficacious in Asian-Americans with chronic hepatitis B infection: a prospective controlled trial.
Martin P. Hann HW. Westerberg S. Munoz SJ. Rubin R. Maddrey WC.
UCLA School of Medicine, Los Angeles, California 90095-1749, USA.
Chronic hepatitis B virus infection is endemic in Asian communities in the United States. The purpose of the current study was to compare the antiviral efficacy of interferon-alpha2b in a group of adult Asian patients chronically infected with hepatitis B with active replication compared to a control group of Caucasian patients treated with the same regimen. Patients with entry aminotransferase (ALT) levels greater than three times the upper limit of normal received interferon-alpha2b, 5 million units, subcutaneously daily for 16 weeks. Patients with pretreatment ALT levels 1.5-3 times the upper limit of normal received prednisone for a total of six weeks prior to interferon starting at 60 mg daily with reduction in dosage by 20 mg every two weeks with a two-week period between finishing prednisone and starting interferon-alpha2b. Eight (62%) of the 13 Asians and six (60%) of the 10 Caucasians cleared HBeAg and HBV DNA from serum (NS). By the end of one year of follow-up after therapy, four (67%) of six Caucasian responders but none of the Asian responders had cleared hepatitis B surface antigen from serum (P < 0.05). Loss of serum markers of active replication appeared less durable in the Asian responders compared to the Caucasians with reappearance of serum HBeAg in two (25%) of eight of the former but only one (17%) of the latter group. Three other Asian patients subsequently redeveloped HBeAg in serum. It is concluded that adult Asian-Americans have an identical initial response rate to antiviral therapy with interferon-alpha2b; however, the response may be less durable and does not usually lead to loss of HBsAg.
Dissolution of gallbladder stones with methyl tert-butyl ether and stone recurrence: a European survey.
Hellstern A. Leuschner U. Benjaminov A. Ackermann H. Heine T. Festi D. Orsini M. Roda E. Northfield TC. Jazrawi R. Kurtz W. Schmeck-Lindenau HJ. Stumpf J. Eidsvoll BE. Aadland E. Lux G. Boehnke E. Wurbs D. Delhaye M. Cremer M. Sinn I. Horing E. v Gaisberg
Center of Internal Medicine, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
Since there are now several ways to treat symptomatic gallstone disease, one is able to select treatment on the basis of the patient's comfort, the practicability, effectiveness, and side effects of the technique, and the relative costs. In order to assess the present status of contact dissolution with methyl tert-butyl ether with regard to these aspects, the present enquiry reports the data of 21 European hospitals. Eight hundred three patients were selected for contact litholysis of cholesterol gallbladder stones using methyl tert-butyl ether. Percutaneous transhepatic puncture of the gallbladder was performed under x-ray or ultrasound guidance. Dissolution rate, side effects, and treatment times of 268 patients from one single center were compared to those of 535 patients from the other 20 centers. Two hundred sixty-four patients were followed for five years to assess stone recurrence. Physicians were asked how they assessed the expenditure of the method, the discomfort to the patients, and the staffing situation. Patients were asked to indicate their acceptance on an analog scale. Puncture was successful in 761 (94.8%) patients. Prophylactic administration of antibiotics was not necessary. Stones were dissolved in 724 (95.1%) patients. In 315 (43.5%) sludge remained in the gallbladder. The most severe complication was bile leakage, which led 12 (1.6%) patients to have elective cholecystectomy. Toxic injuries due to the ether were not reported. Method-related lethality amounted to 0%, 30-day-lethality to 0.4%. Stone recurrence rate was about 40% in solitary stones and about 70% in multiple stones over five years. Patients with multiple stones developed recurrent stones almost twice as often as those with solitary stones. The probability of stone recurrence in patients with sludge in the gallbladder after catheter removal was not statistically significantly different from those without sludge. Seventy to 90% of the centers found the puncture to be simple and not distressing for patients and the relation between expenditure and therapeutic success to be acceptable. The acceptance of contact litholysis by the patients was excellent. Contact litholysis when applied by an experienced team provides real advantages in the treatment of gallstone disease. The method is technically simple, well accepted by the patients, and can be easily applied in community hospitals. Contact litholysis may be of particular value in patients who are not suitable for anesthesia or surgery.
Histological findings of gallbladder mucosa in 95 control subjects and 80 patients with asymptomatic gallstones.
Csendes A. Smok G. Burdiles P. Diaz JC. Maluenda F. Korn O.
Department of Surgery and Pathology, University Hospital, Santiago, Chile.
The histological appearance of gallbladder mucosa in 95 control subjects and in 80 patients with asymptomatic gallstones separated according to age and sex was determined in a prospective study. The number and size of stones in the latter group were also analyzed. Among controls, 33% showed abnormal histological findings, mainly chronic cholecystitis, which increased with age and was frequently seen among women. All patients with asymptomatic gallstones showed chronic cholecystitis and/or cholesterolosis, and 5% showed acute inflammatory changes. In 55% of them a single stone was found. These findings suggest that chronic inflammatory changes can occur in the gallbladder mucosa prior to the appearance of macroscopic stones at the gallbladder.
Risk factors for gallstone disease in Mexicans are similar to those found in Mexican-Americans.
Mendez-Sanchez N. Vega H. Uribe M. Guevara L. Ramos MH. Vargas-Vorackova F.
Biliary Tract Disorders Clinic, Fundacion Clinica Medica Sur and Department of Gastroenterology, Instituto Nacional de la Nutricion, Tlalpan, Mexico City, Mexico.
According to epidemiological studies, gallstone disease is a very common disease in Mexican-Americans and Mexicans. However, the major risk factors for cholelithiasis in Mexicans have not been identified. We designed a case-control study in a group of Mexican subjects with and without gallstone disease confirmed by ultrasound. These subjects were prospectively studied over a three-year period. Clinical and epidemiological data were collected by means of a questionnaire. A total of 1500 subjects were included in this study: 1000 with and 500 without gallstone disease. The major risk factor in both men and women was body mass index [odds ratio (OR) 1.64 and 1.96, respectively; P < 0.008 and 0.001]. In addition, parity was an important factor in women (OR 2.17, P < 0.001), whereas age was associated with gallstone disease in men (OR 1.43, P < 0.001). We found that body mass index, parity, and age were the principal risk factors for gallstone disease in this group of Mexican subjects. These results are similar to those found in Mexican-American populations.
Dixit VK. Prakash A. Gupta A. Pandey M. Gautam A. Kumar M. Shukla VK.
Department of Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
Xanthogranulomatous cholecystitis exists in a small but significant proportion of routine cholecystectomy specimens. A few recent reports have shown a possible association of this disease with carcinoma of the gallbladder. All cholecystectomized specimens were prospectively evaluated over a period of two and half years in a single surgical unit to examine the incidence of xanthogranulomatous cholecystitis and its association, if any, with carcinoma of the gallbladder in an area that is prone to gallbladder diseases. A total of 460 cholecystectomies were performed for various gallbladder diseases. Histological confirmation revealed chronic cholecystitis in 311 (67.6%) cases, carcinoma of the gallbladder in 62 (13.5%), acute cholecystitis in 29 (6.3%), xanthogranulomatous cholecystitis in 41 (8.9%), and xanthogranuloma and carcinoma of the gallbladder in one case (0.2%) only. Almost all cases were suspected to have chronic cholecystitis on clinical and ultrasonographic features. Two specimens on gross examination showed mass lesions, and hence were suspected to be carcinoma of the gallbladder. Subsequent frozen section and histopathology demonstrated xanthogranulomatous cholecystitis. Only one case of xanthogranuloma was found to be associated with carcinoma of the gallbladder but no firm association could be established between xanthogranulomatous cholecystitis and carcinoma of the gallbladder.
Expression of p53 and p21 are independent prognostic factors in patients with serosal invasion by gastric carcinoma.
Ikeguchi M. Saito H. Katano K. Tsujitani S. Maeta M. Kaibara N.
Department of Surgery I, Faculty of Medicine, Tottori University, Yonago, Japan.
To evaluate whether the expression of p53 and that of p21 are independent prognostic factors in patients with advanced gastric cancer, we investigated clinicopathological factors and the expression of p53 and p21 in 158 patients with gastric cancer that had invaded the serosa and who had undergone curative gastrectomy. In multivariate survival analysis of 156 surviving patients, we evaluated the size of the tumor, lymph node metastasis, venous invasion, lymph node dissection, expression of p53, and expression of p21 as independent prognostic factors. Moreover, we divided patients into four groups according to the expression of p53 and p21 in their tumors [group A, p53-/p21-, N = 40 (one died within 30 days of surgery); group B, p53-/p21+, N = 23; group C, p53+/p21-, N = 58; and group D, p53+/p21+, N = 37 (one died within 30 days of surgery)]. The 5- and 10-year survival rates of 39 patients in group A were 71.7% and 64.3%, those of 23 patients in group B were 81.4% and 81.4%, those of 58 patients in group C were 35.6% and 30.2%, and those of 36 patients in group D were 67.9% and 60.7%. The prognosis of patients in group C was poorer than that of patients in the other three groups. This result indicates that the evaluation of the expression of both p53 and p21 expression might provide prognostic information that is more accurate than that provided by evaluation of the expression of p53 alone.
REP-PCR fragments as biomarkers for differentiating gastroduodenal disease-specific Helicobacter pylori strains.
Kwon DH. El-Zaatari FA. Woo JS. Perng CL. Graham DY. Go MF.
Department of Medicine, Veterans Affairs Medical Center, Baylor College of Medicine, Houston, Texas 77030, USA.
We previously identified four potential putative gastroduodenal disease fragments by using the interspersed repetitive extragenic palindromic DNA sequence based PCR (REP-PCR) technique. We investigated these fragments with regard to their disease specificity. The putative disease-specific REP-PCR fragments were cloned, mapped by restriction enzymes, cross-hybridized, and confirmed by Southern hybridization. The four fragments were also used as probes against REP-PCR amplicons from H. pylori isolates obtained from gastritis (N = 20), duodenal ulcer (N = 30), and gastric cancer patients (N = 30). Three of these fragments (1.4- and 0.76-kb for gastritis; 1.35 kb for duodenal ulcer) were amplified without any discrimination between any disease-specific H. pylori isolates. However, amplification following hybridization with the fourth 0.81-kb fragment was observed only from gastritis (60%) and duodenal ulcer (52%) but with none (0%) of gastric cancer patients. Nucleotide sequence analysis of the 0.81-kb fragment revealed that it was an open reading frame of the hypothetical protein HP0373 matched to the position of 380,966 to 383,068 nucleotides of the H. pylori complete genome sequence. Hence, the REP-PCR sequence was not a extragenic palindromic DNA sequence. The hypothetical protein was also present in all the tested isolates. The REP-PCR fingerprinting technique is useful to differentiate disease-specific H. pylori strains based on the interspersed repetitive extragenic palindromic DNA sequences; however, it may not be useful to identify disease-specific virulence determinant(s) without being confirmed by DNA sequence analysis and functional studies.
Prevalence of upper gastrointestinal lesions and Helicobacter pylori infection in Crohns disease.
D'Inca R. Sturniolo G. Cassaro M. di Pace C. Longo G. Callegari I. Rugge M.
Divisione di Gastroenterologia, Cattedra di Istochimica e Immunoistochimica Patologica, Universita di Padova, Italy.
Crohn's disease can affect the upper gut with reported variable frequency, although concurrent Helicobacter pylori infection has been reported to be low. We prospectively investigated the prevalence of esophageal, gastric, and duodenal lesions and Helicobacter pylori infection in 67 Crohn's disease, 41 ulcerative colitis patients, and 43 controls. Symptoms, esophagogastroduodenoscopy, and multiple biopsies were performed on all patients consecutively. Endoscopic lesions were found in 63% of Crohn's disease patients, with a Helicobacter pylori prevalence of 28%. Granulomas were found in three patients. Twenty-two percent of the ulcerative colitis patients had lesions, with a 29% prevalence of Helicobacter pylori infection. Half of the controls had pathological endoscopy, and Helicobacter pylori was positive in 40% of the cases. Subjective symptoms did not predict the presence of endoscopic lesions or Helicobacter pylori infection in inflammatory bowel disease patients. Chronic gastritis and duodenitis are common in Crohn's disease patients, and the majority are not associated with Helicobacter pylori infection.
Rabeprazole in treatment of acid peptic diseases: results of three placebo-controlled dose-response clinical trials in duodenal ulcer, gastric ulcer, and gastroesophageal reflux disease (GERD). The Rabeprazole Study Group.
Cloud ML. Enas N. Humphries TJ. Bassion S.
Eli Lilly and Company, Indianapolis, Indiana, USA.
Rabeprazole, a new proton pump inhibitor, was studied in patients with acid-peptic-related diseases (duodenal ulcer, gastric ulcer, GERD) in three placebo-controlled, double-blind, randomized clinical trials. Men and women over the age of 18 were enrolled if the presence of an active duodenal or gastric ulcer or erosive or ulcerative esophagitis was confirmed on upper gastrointestinal endoscopy. Patients were randomly allocated to either placebo or rabeprazole 20 mg or 40 mg in the duodenal and gastric ulcer protocols or to placebo or rabeprazole 10 mg, 20 mg, or 40 mg in the GERD protocol. All doses of rabeprazole in all three studies were statistically significantly superior to placebo in healing acid-related lesions. There were no treatment differences between the rabeprazole doses in healing active peptic lesions. The incidence of positive [13C]urea breath test for H. pylori was 53% in patients with duodenal or gastric ulcers. H. pylori status was not effected by treatment with rabeprazole.
Empirical therapy versus diagnostic tests in gastroesophageal reflux disease: a medical decision analysis.
Sonnenberg A. Delco F. El-Serag HB.
Department of Veterans Affairs Medical Center and the University of New Mexico, Albuquerque 87108, USA.
Our objective was to describe the conditions that determine the costs of empirical therapy in gastroesophageal reflux disease (GERD). Our design was a threshold analysis using a decision tree. The costs of medications were estimated from the average wholesale prices. The costs of diagnostic procedures were expressed as the sum of physician and facility costs. A decision tree was modeled to calculate the threshold probability of GERD, for which empirical therapy became the preferred management strategy. Bayes' formula was used to transform the sensitivity and specificity of various symptoms and the joint occurrence of multiple symptoms into disease probabilities. The decision in favor of empirical therapy is influenced by four factors: the probability of GERD, the duration or costs of GERD therapy, the costs of erroneous empirical therapy in patients with diagnosis other than GERD, and the costs of diagnostic procedures. In general, the expected benefit of saving the costs of a diagnostic procedure outweighs the costs of occasional erroneous empirical therapy. However, if surgical therapy is considered or antisecretory therapy is administered for a time period of 10 or more years, diagnostic confirmation of GERD should be sought. In the long run, the failure to differentiate between peptic ulcer and GERD results in the highest cost associated with erroneous empirical therapy. In patients with multiple characteristic symptoms of GERD, the diagnosis can be ascertained with sufficient confidence to warrant empirical therapy.
Prevalence of Barretts esophagus in Hispanics is similar to Caucasians.
Bersentes K. Fass R. Padda S. Johnson C. Sampliner RE.
Arizona Health Sciences Center and Tucson Veterans Affairs Medical Center, Department of Internal Medicine, 85723, USA.
Barrett's esophagus (BE) is considered to be a disease of white males with a prevalence ranging from 0.5 to 4.0% in patients undergoing upper endoscopy (EGD) for any indication, and from 12 to 15% in patients with gastroesophageal reflux disease (GERD). The prevalence of BE in Hispanics is not known, but it is assumed to be lower. The aims of this study were to determine the prevalence of BE in Hispanic patients and to compare demographic and endoscopic characteristics with Caucasian patients with BE. Records of patients undergoing an EGD between October 1993 and October 1996 were retrospectively reviewed. Patients were included in the study only if they had columnar-appearing esophageal mucosa at endoscopy and intestinal metaplasia with Alcian blue-staining goblet cells on biopsy. An extensive chart review was performed in patients with BE. There were 75 new cases of BE discovered: 60 (80%) were Caucasians, 6 (8%) Hispanics, 1 (1.4%) Native American, and 8 (10.6%) patients with either unknown or unconfirmed ethnicity. Of the 75 patients, 74 male, and the mean age was 65 +/- 11.4 years (range 36-92 years). The prevalence of BE in Caucasians and Hispanics undergoing EGD for any reason was similar (5.3% and 3.8%, respectively, P = 0.563). The prevalence of BE in patients presenting with GERD symptoms was also similar between Caucasians and Hispanics (25% and 16%, respectively, P = 0.304). The two groups did not differ significantly with respect to age, symptoms, habits, or endoscopic findings. In conclusion, the prevalence of BE among Hispanic patients is similar to Caucasian patients, an unexpected finding.
Eosinophil activation in ulcerative colitis: studies on mucosal release and localization of eosinophil granule constituents.
Raab Y. Fredens K. Gerdin B. Hallgren R.
Department of Surgery, University Hospital, Uppsala, Sweden.
Activation of eosinophil granulocytes (eosinophils) seems to contribute to the pathophysiology of several inflammatory conditions. This process was evaluated in 18 patients with ulcerative colitis and in 18 healthy controls using intraluminal segmental perfusion of the sigmoid colon and rectum and immunoanalysis for eosinophil cationic protein (ECP) in the perfusate. Immunohistochemistry for eosinophils and neutrophils was made in simultaneously taken biopsies and in biopsies from surgical specimens taken from additional 10 patients. The mucosal release of ECP was increased severalfold in patients with UC. The bowel biopsies demonstrated a lamina propria infiltrated with eosinophils. The degree of eosinophil activation/degranulation was related to the intensity of the inflammatory reaction. Activated eosinophils and extracellular deposits of ECP were, in particular, seen in crypt abscesses and in areas with damaged surface epithelium. Since ECP is highly cytotoxic, its release at the site of inflammatory bowel lesions might reflect a potential pathophysiological mechanism.
Plasma and mucosal fatty acid pattern in colectomized ulcerative colitis patients.
Esteve M. Navarro E. Klaassen J. Abad-Lacruz A. Gonzalez-Huix F. Cabre E. Ramos E. Condom E. Fernandez-Banares F. Pastor C. Humbert P. Marti-Rague J. Gassull MA.
Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain.
Patients with inflammatory bowel disease (IBD) have increased plasma n3 polyunsaturated fatty acids (PUFAs), which in ulcerative colitis (UC) patients persists six months after colectomy, suggesting a primary abnormality in fatty acid (FA) metabolism in IBD. This finding needed to be confirmed in a larger series of UC long-term colectomized patients. We aimed to assess the plasma FA pattern in UC colectomized patients with either Brooke's ileostomy (UC-BI) or ileal pouch anal anastomosis (UC-IPAA) and the mucosal FA pattern in the ileal reservoir of the UC-IPAA patients. Plasma FAs were assessed in 63 UC colectomized patients (31 with BI and 32 with IPAA) and 30 controls. In 26 UC-IPAA (8 with pouchitis and 18 without pouchitis) and in 13 healthy controls gut mucosal FAs were also investigated. FAs were detected by capillary column gas-liquid chromatography. Increased levels of saturated fatty acids (SFAs) and decreased percentages of monounsaturated fatty acids (MUFAs) were observed in both groups of patients. There were no changes in plasma n3 and n6 PUFAs. The mucosal FA pattern of the ileal reservoir consisted of increased long-chain PUFAs, specially n6 PUFA, and a decrease of their essential precursors. High percentages of SFAs and low percentages of MUFAs were also seen. The plasma FA profile previously described in IBD is not observed long-term after colectomy in UC, suggesting that it is related with the presence of inflamed intestine. High concentrations of SFAs and decreased percentages of MUFAs might represent early events in disturbed FA metabolism in IBD. The changes in FAs of the ileal reservoir, which closely resemble those found in human and experimental IBD, probably represent a common pattern of intestinal inflammation.
Intestinal expression of human heat shock protein 90 in patients with Crohns disease and ulcerative colitis.
Stahl M. Ludwig D. Fellermann K. Stange EF.
Department of Internal Medicine I, Medical University of Lubeck, Germany.
Heat shock proteins are induced by several stress factors and are potential antigens in autoimmune disorders. Expression of heat shock protein 90 (HSP 90) was investigated in patients with inflammatory bowel disease and normal controls. We combined western blot analysis with laser densitometry for quantitation. Localization of HSP 90 was investigated by immunohistochemistry. Western blots showed a significant mucosal expression of HSP 90, which was comparable in patients and controls. There was also no difference between normal and inflamed mucosa in inflammatory bowel disease. In immunohistochemical staining studies, HSP 90 was detected in epithelial cells, mononuclear cells, giant cells, nerve cells, and endothelial cells of small vessels. There was no difference in the intensity of staining or localization in patients with inflammatory bowel disease compared to controls. These findings render a potential protective or immunogenic function of HSP 90 in inflammatory bowel disease unlikely.
Glutathione content of colonic mucosa: evidence for oxidative damage in active ulcerative colitis.
Holmes EW. Yong SL. Eiznhamer D. Keshavarzian A.
Department of Pathology, Loyola University Stritch School of Medicine, Maywood, Illinois 60153, USA.
Oxidative stress appears to play a role in the tissue damage of active ulcerative colitis, and it has been suggested that a defect in mucosal antioxidant defenses is a etiological factor in the disease. This study was undertaken to investigate the mucosal content and oxidation state of glutathione in ulcerative colitis in the active and inactive states and to examine the relationship between glutathione content and disease activity in this patient population. Endoscopic biopsies of colon mucosa were collected from normal subjects, from macroscopically normal tissue of patients with inactive and active ulcerative colitis, and from inflamed tissue of patients with active ulcerative colitis. The mucosal contents of GSH and GSSG were determined by liquid chromatography. We found no significant differences in tissue contents of reduced glutathione among the four groups. The median tissue level of oxidized glutathione in inflamed mucosa from patients with active ulcerative colitis was increased 1.7-fold (P = 0.017) over that of patients with inactive disease. The oxidized glutathione content of the mucosa also showed significant positive correlations with clinical and histological indices of disease severity among ulcerative colitis patients. In conclusion, a change in the redox status of mucosal glutathione is associated with inflammation and disease activity in ulcerative colitis. This change appears to be a consequence of inflammation rather than a pathogenic factor for the disease.
Sucrosemia in untreated celiac disease: a potential screening test.
Cox MA. Lewis KO. Cooper BT.
Department of Clinical Chemistry, City Hospital, Birmingham, UK.
During studies to develop serum tests of small intestinal permeability, we detected an unidentified disaccharide in HPLC traces of sera from untreated celiacs. This present study aimed to identify the disaccharide and determine whether the presence of the disaccharide in the serum after an oral challenge had potential as a simple screening test for celiac disease. The disaccharide was identified as sucrose by incubation studies of sera with disaccharidases. Twenty untreated celiacs, 15 treated celiacs, and 20 normal or dyspeptic controls were studied for the presence of sucrose in their serum after an oral load (8 g). The results in celiacs were compared with the presence of serum IgA endomysial antibodies. The 10 normal controls were also given a larger sucrose challenge (50 g). Ten of the untreated celiacs and 10 controls had their brush border disaccharidase activities measured. Sucrose eluted in the same position as the unidentified disaccharide in the HPLC trace and the latter could be removed by incubation with sucrase. All untreated celiacs but none of the treated celiacs had sucrose in their serum after the 8-g oral challenge. None of the controls had sucrose in their serum after the 8-g or 50-g challenges. Three untreated celiacs were IgA endomysial antibody negative as were all the treated cases. Brush border sucrase activity was low in untreated celiac disease. The presence of sucrose in the serum after an oral load shows promise as a noninvasive test for celiac disease.
Premorbid hair growth over the trunk and severity of alcohol-related liver disease.
Kumar N. Anand BS.
Department of Gastroenterology, G.B. Pant Hospital, New Delhi, India.
It is unclear why only a minority (