The nutritional benefits of lactic acid bacteria in fermented dairy products have been well documented, especially in terms of weight gain and feed efficiency, but not in terms of small intestine adaptation. The effects of a diet supplemented (30% wt/wt) with milk fermented either by Lactobacillus casei DN-114 001 or yoghurt for 3 or 15 days were investigated in the small intestine of mice by morphometry, kinetic analysis and determination of brush-border enzyme activities. Results were compared with those obtained with standard or milk isocaloric diets. Cell proliferation and villous area were significantly increased in the proximal intestine of mice fed the fermented-milk-supplemented diets for 3 days and were associated with hypertrophy and hyperplasia of Paneth and goblet cells. Lactase-specific activity was increased by fermented-milk diets at days 3 and 15, whereas there was no variation in maltase-specific activity. Alkaline phosphatase-specific activity was increased after 3 days of the three tested diets in the whole intestine, and after 15 days in the proximal intestine. Aminopeptidase activity was increased in the distal part of the intestine after 3 days of the 3 diets. Our findings suggest that diets supplemented with fermented milks have a positive effect on the trophicity of the mucosa in the small intestine of mice.
We intended to evaluate the association between specific human leukocyte antigen (HLA)-DRB1 gene polymorphism and antiviral response to lamivudine (LAM) therapy in chronic hepatitis B (CHB) patients.
Six-digit HLA-DRB1 genotypes were determined using sequence-based typing in 334 CHB patients initially treated with LAM for at least 12 months. Antiviral response was evaluated every 3-6 months during LAM therapy.
Median age of the subjects was 43 years (range, 16-72). Median duration of LAM therapy was 69 months (range, 13-140). Median baseline serum hepatitis B virus (HBV DNA) level was 7.0 log(10) copies/ml (range, 5.5-9.1). At 12 months of LAM therapy, serum HBV DNA was undetectable by solution hybridization method in 308 (88%) patients. Among 25 HLA-DRB1 alleles identified, HLA-DRB1*090102, *080302, and *070101 were the most frequent alleles (>10%). HLA-DRB1*010101 was identified in 5.4% (18/334). The frequency of the HLA-DRB1*010101 allele was significantly lower in patients with virological response at 12 months of LAM therapy than in patients without it (4.2 vs. 19.2%, p = 0.025). The other HLA-DRB1 alleles were not associated with virological response. HBeAg loss/seroconversion and alanine aminotransferase normalization were not associated with HLA-DRB1 alleles.
The HLA-DRB1*010101 allele is closely associated with poor virological response to initial LAM therapy in CHB patients.
The aim of the study was to evaluate the frequency of anatomic variations of the hepatic duct bifurcation using magnetic resonance cholangiopancreatography (MRCP).
A total of 1,160 consecutive patients, referred to our department for MRCP due to suspected pancreatobiliary disease or before liver transplantation, were reviewed retrospectively. A total of 149 patients with less than optimal results due to imaging limitations or secondary differentiations of bile duct anatomy were excluded from the study. The final study population was composed of 1,011 cases.
Of the 1,160 patients, 149 were excluded from the analysis. Typical biliary anatomy was observed in 79.4% of cases, but female potential living liver donors more frequently presented an anatomic variation. Typical anatomy was present in 75.7% of the females and 85.3% of the males (p < 0.05). Out of the remaining 1,011 patients, 208 (20.57%) were diagnosed with different levels of various anatomic variations of the intra- and extrahepatic biliary ducts. Of the 208 cases with diagnosed variations, 204 (98.07%) and 4 (1.92%) turned out to have 1 and 2 different variations, respectively. The trifurcation variant was observed in 81 cases (8.01%), while 73 subjects (7.23%) had an aberrant right biliary duct draining into the common hepatic duct. A right dorsocaudal branch draining into the left hepatic duct was present in 42 cases (4.15%). Four cases (0.4%) had 2 different variations and 8 (0.8%) had uncommon anatomic variations.
Typical intrahepatic biliary anatomy is present in about 80% of the inhabitants of the Aegean region of Turkey, but anatomic variants seem to be more frequent in females as compared to males. Trifurcation was the most common anatomic variation in our study population. The presence of an aberrant right hepatic duct emptying into the common hepatic duct was the second most common observation amongst our findings.
Background and aims:
Gastroesophageal reflux disease (GERD) reportedly has increased in prevalence while Helicobacter pylori infection and peptic ulcer disease have been on the decrease. The aim of the present study was to examine the prevalence of GERD as well as the clinical, endoscopic and histologic variables that associate with GERD in patients referred for endoscopy.
Patients and methods:
The study population was drawn from 1,562 consecutive patients referred for endoscopy. The exclusion criteria were previous H. pylori eradication, gastric surgery, anemia and weight loss. Thus 1,128 patients were enrolled in the present study.
Of the 1,128 patients, 199 (18%) were referred for endoscopy due to heartburn and/or regurgitation. GERD, defined as chronic (>6 months) heartburn and/or regurgitation with or without erosive esophagitis, Barrett's esophagus, esophageal ulcer or stricture, was detected in 248 (22%) patients. Of the 248 GERD patients, 81 (33%) had endoscopy-negative GERD, but of those aged <50 years (n = 67), 57 (85%) were endoscopy-negative. The overall incidence of GERD was 307 per 100,000 population/year and that of endoscopy-positive GERD 207/100,000/year. The positive and negative predictive values of heartburn and regurgitation for endoscopy-positive GERD were 0.37 (95% CI 0.31-0.44) and 0.90 (95% CI 0.88-0.92), respectively. Independent risk factors for GERD were male sex (OR 1.9, 95% CI 1.3-2.7), previous medication for upper gastrointestinal symptoms (OR 2.7, 95% CI 1.7-4.1), the use of nonsteroidal anti-inflammatory drugs (NSAIDs; OR 2.0, 95% CI 1.3-3. 0), histologic esophagitis (OR 2.2, 95% CI 1.5-3.2) and incomplete intestinal metaplasia at the gastroesophageal junction (OR 1.7, 95% CI 1.0-3.1). Chronic gastritis was protective against GERD (OR 0.7, 95% CI 0.5-0.9). No association was observed between GERD and H. pylori infection. The risk of patients aged <50 years (n = 407) of having major lesion (Barrett's esophagus, esophageal stricture, peptic ulcer, esophageal/gastric carcinoma) was significantly lower than that of patients aged >50 years (n = 721; OR 0.5, 95% CI 0.3-0. 9, p = 0.01).
The correlation between reflux symptoms and endoscopy-positive GERD is poor and most GERD patients aged <50 years have endoscopy-negative GERD. The use of NSAIDs is a risk factor for GERD, whereas chronic gastritis, but not H. pylori infection, may protect against GERD. Incomplete intestinal metaplasia at the gastroesophageal junction is associated with GERD.
The discriminative value of patient characteristics and dyspeptic symptoms for upper gastrointestinal endoscopic findings was prospectively assessed in 1,147 patients attending for their first diagnostic endoscopy and who answered paper (n = 431) or computerized (n = 716) questionnaires. The questionnaires provided detailed information concerning present dyspeptic symptoms, with special attention to provoking and/or relieving factors, and smoking and/or drinking habits. In logistic regression models each of a number of 'specific endoscopic diagnoses' was contrasted with normal endoscopy (n = 390), and 'relevant endoscopic disease' (oesophagitis, peptic ulcers, cancers; n = 269) was contrasted with 'irrelevant' and normal endoscopic findings (n = 878). From the regression model a receiver operating characteristic (ROC) curve could be constructed, and the area under the ROC curve (AUC) was calculated to summarize the discriminative power of the regression model. The best discrimination from patients with a normal endoscopy was achieved for patients with gastric (AUC = 0.86) or duodenal (AUC = 0.85) ulcers, followed by patients with hiatus hernia (AUC = 0.78 or oesophagitis (AUC = 0.77). The discriminative performance of the regression models was somewhat less for duodenitis/bulbitis (AUC = 0.75) and endoscopic gastritis (AUC = 0.73). In an open-access endoscopy unit setting, the value of preinvestigation history-taking for the prediction of clinically relevant endoscopic disease was very limited (AUC = 0.63).
This retrospective study aimed to determine risk factors associated with serious complications of endoscopic submucosal dissection of gastric tumors in multicenters compared between high- and low-volume centers.
Between 2001 and 2010, gastric endoscopic submucosal dissection was performed in 1190 lesions of 1082 patients in five hospitals in Saga, three high-volume and two low-volume centers. Risk factors for serious complications were evaluated. Patients' background characteristics were evaluated, including anticoagulants use and underlying diseases.
Postoperative bleeding was detected in 75 patients (6.9%), and perforation was detected in 40 patients (3.7%). Most postoperative bleeding and perforation cases were recovered with endoscopic procedures, although one case of each complication was treated by emergency surgery. Multivariate analysis indicated that risk factors for perforation were tumor location, massive submucusal invasion, endoscopists' experience of 100-149 cases and hypertension, and that risk factors for postoperative bleeding were tumor location, resected tumor size, and scar lesion. The serious complications were not different between high- and low-volume centers.
The present study indicated that risk factors for perforation during endoscopic submucosal dissection were tumor, endoscopist and patient related, although risk factors for postoperative bleeding were tumor related. There was no difference in complications between high- and low-volume centers.
1,2-Dimethylhydrazine(DMH) was administered s.c. to a group of 20 inbred BD-IX rats at the dose of 15 mg/kg body weight, weekly for 7 months. Intestinal adenocarcinoma have been found in all of the treated animals, often associated with hyperplastic or dysplastic lesions. The intestinal cancers gave metastases in 14 animals. The low incidence of extra-intestinal malignancies, the relatively short induction time, the similarity to human colorectal adenocarcinoma, make the DMH-induced intestinal cancer a highly effective experimental model.
Multiple colorectal adenocarcinomas were found in Sprague-Dawley rats after intrarectal injection of 1,2-dimethylhydrazine (DMH). These lesions along with mild hyperplasia of the surrounding mucosa developed within 34 weeks after either 3 or 8 injections of 250 mg DMH/kg body weight.
Calcium and magnesium transport at different luminal concentrations (1.25, 2.5, 5 and 10 mmol/l) and under the influence of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] were studied in vivo at the perfused colon of the rat. Net absorption of calcium and of magnesium were saturated with increasing concentrations of the perfusate. Net absorption of one ion was not affected by an increasing concentration of the other ion. 1,25(OH)2D3 (100 ng/day given subcutaneously for 4 days) stimulated net absorption of calcium and of magnesium. Presence or absence of calcium or magnesium, respectively, had no effect on the absorption of the other ion under 1,25(OH)2D3 stimulation. The results demonstrate that the colon of the rat is capable of absorbing calcium as well as magnesium. These observations suggest that calcium and magnesium in the rat colon are absorbed by two separate active transport mechanisms, which both are sensitive to 1,25(OH)2D3.
Mini-laparoscopy has, since its first description in 1998, proven to be a valuable diagnostic method in liver diseases. We re-evaluated the significance of mini-laparoscopy for diagnosis and staging of liver disease and primary liver and bile duct cancer.
Patients and methods:
1,788 consecutive patients who received a diagnostic mini-laparoscopy between 10/1998 and 06/2011 were included in this retrospective cohort study.
In chronic liver disease, cirrhosis was detected by mini-laparoscopy in 27% of cases. A comparison of microscopic versus macroscopic diagnosis of cirrhosis revealed a sampling error for histology alone of 21%. Macroscopic inspection of the liver surface contributed to the diagnosis of unknown liver diseases in approximately 38%. In patients with bile duct or liver cancer, mini-laparoscopy led to upstaging of the disease in 33 and 23%, respectively. Major complications (bowel perforation and delayed bleeding) occurred in 0.39% of cases.
Mini-laparoscopy is a valuable procedure with significant diagnostic impact in known and unknown inflammatory and malignant liver diseases. It can be safely performed even in patients with acute liver failure and severe coagulopathy and the diagnostic value does not differ from diagnostic laparoscopy performed with standard instruments.
(13)CO(2) is decreased in patients with end-stage liver disease by the [1-(13)C]-phenylalanine breath test. Decreased (13)CO(2) is supposed to be caused by the decreased ability of the liver to oxidize phenylalanine. However, no direct evidence has been reported.
The [1-(13)C]-phenylalanine breath test was performed in galactosamine hepatitis rats (n = 14) and control rats (n = 8). Plasma phenylalanine concentration before intravenous administration of [1-(13)C]-phenylalanine, the elimination rate of phenylalanine and the phenylalanine hydroxylase (PAH; EC 188.8.131.52) activity of the whole liver were examined.
Increase of (13)CO(2) in the breath [Delta(13)CO(2) ( per thousand)] of galactosamine hepatitis rats 2 min after administration of [1-(13)C]-phenylalanine was only 1/5 of that in control rats. The concentration of plasma phenylalanine and the elimination rate of plasma phenylalanine in hepatitis rats did not show significant differences compared to control rats. On the other hand, a clear difference in the activity of PAH was observed between hepatitis rats and control rats. Delta(13)CO(2) ( per thousand) 2 min after administration of [1-(13)C]-phenylalanine was highly correlated to the PAH activity of the whole liver (r = 0.917).
It was strongly indicated that decreased Delta(13)CO(2 ) in hepatitis rats was the result of decreased activity of PAH.
Endotoxemia, measured by Limulus amebocyte lysate (LAL) assay, was found to be present in 34 (46%) out of 72 patients with liver cirrhosis and in 7 (22%) out of 32 patients with chronic active hepatitis (CAH). In cirrhotics, no difference in the alteration of liver function tests and renal function was found between the two groups. However, 18 months mortality was higher in the group with endotoxemia in respect to the group without endotoxemia (p less than 0.05). In CAH patients, the Limulus-positive group showed a higher level of serum gamma-globulins, compared to the Limulus-negative group (p less than 0.005). Moreover, CAH patients with a positive LAL test showed marked histological activity and bridging necrosis more frequently than those with a negative test. This suggests that in these patients the appearance of endotoxemia may indicate a more advanced stage of the disease.
The frequency of acute and chronic pancreatitis is 3.3 and 2.1%, respectively, in 107,754 adult autopsies in Japan. Acute pancreatitis is highly associated with liver diseases of various etiologies such as subacute hepatitis (16.1%), fulminant hepatitis (13.5%), biliary cirrhosis (10.5%), cholangiocarcinoma (8.6%) and postnecrotic cirrhosis (7.1%). Chronic pancreatitis is also closely related to various liver diseases. It is suggested that the portal venous stasis in liver diseases may predispose the patients to develop pancreatitis regardless of the etiology of liver diseases.
The effects of TY-10957, a stable PGI2 derivative, on gastroduodenal lesions and secretory responses were examined in rats and compared with those of ornoprostil, a PGE1 derivative. Orally administered TY-10957 dose dependently prevented gastric lesions induced by ethanol/HC1 (60% ethanol in 150 mM HCl) and duodenal ulcers induced by mepirizole (200 mg/kg); a significant effect was obtained at 3 micrograms/kg or greater in the former and at 300 micrograms/kg in the latter. Intraduodenally administered TY-10957 had minimal effects on gastric acid secretion, and at the highest dose (300 micrograms/kg) both the basal acid output and that stimulated by histamine (20 mg/kg) were significantly reduced by about 40%. TY-10957 (30-300 micrograms/kg s.c.) produced a marked increase of alkaline secretion in both stomach and duodenum of anesthetized rats, and these effects were significant at 30 micrograms/kg in the stomach and at 100 micrograms/kg in the duodenum. On the other hand, ornoprostil produced a potent and significant inhibition against ethanol/HCl-induced lesions (greater than 1 microgram/kg), but had no effect on mepirizole-induced duodenal ulcers. This PGE1 derivative had no influence on both basal and stimulated acid secretion and did not significantly affect alkaline secretion even at 100 micrograms/kg. These results suggest that TY-10957 has a protective action on both gastric and duodenal mucosa. The mechanism of duodenal antiulcer effect may involve both inhibition of acid and stimulation of alkaline secretion, while the gastroprotective action of this agent may be attributed to other factors.
Liver transplantation (LTx) is the only established treatment in patients with end-stage primary biliary cirrhosis (PBC). Although short-term survival after LTx in this group of patients is usually good, few data exist on the long-term survival. The optimal timing of transplantation is difficult. Thus, the aims of this study were to assess the long-term survival of patients with PBC after LTx and to identify potential predictive factors for a positive outcome.
Survival of 28 patients with PBC who underwent LTx between 1985 and July 1999 in a single center was studied by Kaplan-Meier analysis and was compared to predicted survival without LTx using established prognostic models for PBC, the Mayo and European risk scores. Potential prognostic parameters obtained before LTx were tested for correlation to survival. Rates of bone fractures as markers of hepatic osteodystrophy were compared before and after LTx.
Median follow-up after LTx was 90 months with a maximum of 140 months. Actuarial survival of patients with PBC was 89% after 1, 5, and 10 years and was significantly better than estimated survival without LTx after 1-7 years as calculated by the Mayo and European risk scores. Of several parameters tested, only serum bilirubin and the prognostic scores, but no other liver function tests obtained immediately prior to transplantation were significantly correlated with survival after LTx. The duration of intensive care after LTx was not associated with any parameters obtained before LTx. Bone fractures were diagnosed in 43% of patients of whom the vast majority were osteopenic before LTx as determined by osteodensitometry.
Long-term survival of a well-defined group of patients with PBC was excellent after LTx and was inversely correlated with preoperative serum bilirubin levels as well as Mayo and European risk scores.
Various tumors of neuroendocrine origin that have amine precursor and decarboxylation (APUD) characteristics can be visualized in vivo after intravenous injection of the somatostatin analogue [123I-Tyr3]-octreotide. However, the relatively short effective half-life of this compound and the high background of radioactivity in the abdomen are drawbacks in its application. Therefore, an 111In-coupled somatostatin analogue ([111In-DTPA-D-Phe1]-octreotide) was developed. This analogue is excreted mainly via the kidneys, 90% of the dose being present in the urine 24 h after injection. Using 111In-octreotide scintigraphy, 7 out of 7 gastrinomas, 4 out of 7 insulinomas, 1 out of 1 glucagonoma, 3 out of 3 unclassified apudomas, but none out of 18 exocrine pancreatic carcinomas were visualized. Also, 19 out of 19 carcinoids, 15 out of 15 glomus tumors, 8 out of 12 medullary thyroid carcinomas, 6 out of 6 small cell lung carcinomas, 4 out of 4 growth hormone-producing and 6 out of 9 clinically nonfunctioning pituitary adenomas were visualized. Apart from APUD-cell-derived tumors, 111In-octreotide scintigraphy was also successfully applied to visualize breast cancer, lymphomas and granulomas. In 39 out of 50 patients with breast carcinoma, 10 out of 11 patients with non-Hodgkin lymphomas, 3 out of 3 patients with Hodgkin's disease, and 8 out of 8 patients with sarcoidosis, tumor sites accumulated radioactivity during octreotide scintigraphy. In a considerable number of patients with carcinoids and glomus tumors, but also in patients with granulomas and lymphomas, 111In-octreotide scintigraphy revealed more tumor sites than did conventional imaging techniques.(ABSTRACT TRUNCATED AT 250 WORDS)
The fecal excretion of 111In-oxine-labeled autologous granulocytes was determined in 58 patients with Crohn's disease. A representative analysis of the total amount of excreted cells requires a 4-day stool sampling at least in those patients suffering from Crohn's ileitis or ileocolitis. Various laboratory tests (Orosomucoid, alpha 1-antitrypsin, C-reactive protein, erythrocyte sedimentation rate, leukocytes, thrombocytes, albumin, Fe, alpha 1-globulin and alpha 2-globulin) and the van Hees index significantly correlated with this specific estimate of intestinal inflammation, indicating that it is of little importance which one is clinically used for the assessment of inflammatory activity in Crohn's disease.
The value of the Crohn's disease activity index (CDAI) in defining clinical remission in Crohn's disease has been assessed in 71 studies using a new method to quantitate gut inflammatory activity: faecal 111In-labelled granulocyte excretion. The range of faecal 111In granulocyte excretion in the irritable bowel syndrome was found to be 0.2-1.9% (mean +/- SD 0.98 +/- 0.55%) of injected dose. 63 (89%) of studies with a CDAI less than 150 and 88% of studies with a serum albumin greater than 35 g/l had faecal 111In granulocyte excretion above the upper limit found in the irritable bowel syndrome ranging from 2.4% to 40%. This study shows that the majority of patients with Crohn's disease in clinical remission have significant gut inflammatory activity. Whether treatment of this activity will alter the natural history of the disease needs prospective evaluation.
In a double-blind, dose comparison multicenter trial 115 patients with duodenal ulcer were treated with either 20 or 30 mg oral omeprazole once daily for 4 weeks. There was no difference in the healing rates for the two groups after 2 and 4 weeks. After 2 weeks with 20 and 30 mg healing frequencies were 79.0 and 72.7%, after 4 weeks 96.5 and 92.7%. No difference was observed between the groups in the number of pain episodes during day and night. No side effects to the drug occurred. A daily dose of 20 mg omeprazole may be effective in ulcer therapy.
118 patients who had recovered from acute pancreatitis underwent endoscopic retrograde pancreatography (ERCP) during a long-term follow-up (mean 4.4 years, range 1-17) to investigate the frequency and features of residual ductal lesions. Oedematous and necrohaemorrhagic pancreatitis occurred in 35 and in 83 patients, respectively. The aetiology was biliary (39 patients), alcoholic (32), biliary-alcoholic (18) and miscellaneous (29). After oedematous pancreatitis, ERCP was normal in 31, showed obstructive pancreatitis in 2 and a slight localized and smooth stricture of the main duct in 2 patients. After necrotizing pancreatitis, 29 patients showed ductal changes without features of chronic pancreatitis, 7 obstructive, 3 chronic calcifying pancreatitis and 44 normal pictures. In 17 patients submitted to two or three ERCPs during a mean 10-year follow-up, the ductal appearance was unchanged in 12, worsened in 3, and improved in 2 patients. The aetiology of pancreatitis and frequency of recurrences was similar in patients with or without scarring lesions. We conclude that residual ductal lesions are common after acute necrotizing pancreatitis.
RMI 12330 A, a compound of the lactamamide series, is a potent inhibitor of vasoactive intestinal polypeptide(VIP)- and prostaglandin (PG)-stimulated colonic secretion in the rat. This substance was tested on the adenylate cyclase system in human colonic mucosa. RMI 12330 A inhibited PGE2-, 16,16-dimethyl-PGE2- as well as VIP-sensitive adenylate cyclases in a dose-related manner. Half-maximal inhibition of hormone-stimulated enzyme activities occurred at a lactamimide concentration of about 0.15 mM. Lactamimide inhibition was non-competitive. Our results are compatible with the concept of RMI 12330 A acting as an inhibitor of colonic secretion via inhibition of hormone-sensitive adenylate cyclase. Since basal, NaF- and guanylyl-imidodiphosphate-stimulated enzyme activities were also affected by this compound, we may conclude that RMI 12330 A is a non-specific inhibitor of the human colonic adenylate cyclase system.
This prospective study was designed to validate a novel biopsy urease test as well as a simplified 13C-urea breath test for the detection of Helicobacter pylori. In addition, the hypothesis was tested that both the reaction velocity of the urease test and the 13CO2 excess of the urea breath test may allow a prediction of the severity of gastritis. Seventy dyspeptic patients with unknown H. pylori status were included. The H. pylori status was assessed by means of culture and histology after Warthin and Starry stain. One antral and one body biopsy specimen were separately analyzed by the novel biopsy urease test (HUT). Also, a 13C-urea breath test using 75 mg 13C-labelled urea and orange juice as test meal was performed in all patients. Forty-seven patients (67%) were H. pylori positive as judged from histology and culture. In 46 patients, H. pylori infection was also detected by the novel biopsy urease test and by the urea breath test as well (sensitivity 97.9%). False-positive results were not observed by either method (specificity 100%). Both the reaction velocity of the urease test and the 13CO2 excess of the breath test significantly correlated with H. pylori density and grade and activity of gastritis. The determination coefficients, however, indicated that both methods allow a reliable prediction of the severity of gastritis only in about 40-50% of the patients. In conclusion, the novel biopsy urease test and the simplified 13C-urea breath test proved to be highly accurate in diagnosing H. pylori infection. Despite a significant correlation, neither the reaction velocity of the urease test nor the 13CO2 excess of the breath test are clinically useful for the prediction of the severity of gastritis.
The (13)C-octanoic acid breath test is a convenient method for assessing gastric emptying (GE). Success depends on obtaining a well-characterized time profile of the excretion of label in breath, which may not be the case if GE is delayed.
To use Bayesian techniques in conjunction with hierarchical modelling as a method to increase the success of the modelling process.
Retrospective analysis of 164 individual breath tests using the WinBUGS program. The approach was tested by analysing the complete dataset simultaneously, and also as individual studies.
The time required for Bayesian modelling was comparable with that needed for the usual methods. The results obtained were almost identical to those obtained from conventional modelling for well-behaved breath tests, but much more realistic in cases where the experimental data was poor, or when GE was delayed.
The use of Bayesian estimation of the parameters of the (13)C-octanoic acid breath test is demonstrated. By adopting a hierarchical model, realistic values for the lag phase and half-emptying time were obtained in situations when conventional parameter estimation failed. This is particularly relevant when GE is unexpectedly delayed. We recommend that WinBUGS become the method of choice for analysing breath test data.
We investigated the diagnostic properties of the (13)C-urea breath test ((13)C-UBT) prospectively. These are well validated in nonresected patients before and after treatment of Helicobacter pylori infection but not in patients with partial gastric resection due to peptic ulcer disease.
Hospitalized patients with previous gastric resection and indications for upper gastrointestinal endoscopy were recruited for the study. Biopsy specimens were obtained from the fundus mucosa and the gastric remnant adjacent to the gastroenteric anastomosis for histological examination and rapid urease test (HUT test). Histological slides were evaluated after hematoxylin and eosin and Warthin-Starry dye staining. 200 ml orange juice was given orally after two baseline breath samples had been taken, and 30 min after ingestion of 75 mg (13)C urea two more breath samples were obtained and analyzed by ratio mass spectrometry. The Warthin-Starry dye-stained sample was taken as reference.
68 patients (47 male, 21 female, mean age 62 years; 52 Billroth II resection, 17 Billroth I resection) were included in the study. The overall prevalence of histologically proven H. pylori infection was 36.7%. The sensitivity of the (13)C-UBT was 52%, the specificity 93%. The positive predictive value was 81.25%, the negative predictive value 76.9% and the accuracy was 77.9%. The sensitivity of the HUT test reached 60%, and the specificity 97%.
The diagnostic accuracy of (13)C-UBT compared with the Warthin-Starry dye staining is low. The breath test, performed in the above-described manner, cannot be recommended as a noninvasive diagnostic tool for diagnosis of H. pylori infection in patients after partial gastrectomy as a result of peptic ulcer disease.
Using a rat model of hepatectomy, we investigated whether the severity of hepatopathy could be quantitatively measured from changes in expiratory (13)CO(2) levels after intravenous administration of [1-(13)C]galactose. MATERIALS ANd
Under nembutal anesthesia, 100 mg/kg [1-(13)C]galactose was administered to rats via the femoral vein, and expiratory (13)CO(2) levels were measured for 60 min. Then, 30, 70 or 90% hepatectomy was performed. In the control group, simple laparotomy was performed. Breath test was conducted 20 min after laparotomy. We examined the correlation of total (13)CO(2) output (S) or single point (13)CO(2) level (SP) every 5 min until 30 min, and at 45 and 60 min with liver weight/body weight (LW/BW) (%).
In the control group, the breath test graph reached a plateau level, but in all groups undergoing hepatectomy a plateau level was not reached during measurement. The correlation coefficient between S(30) after [1-(13)C]galactose administration and LW/BW was 0.889 (p< 0.0001). The correlation coefficient between SP(25) after [1-(13)C]galactose administration and LW/BW was highest, 0.923 (p< 0.0001).
In the breath test with intravenously administered [1-(13)C]galactose, hepatopathy could be evaluated by measuring S(30) and hepatopathy could be more accurately quantitatively evaluated by measuring SP(25) over a short period.
Human pancreatic cationic trypsin labelled with 131I was administered into the duodenum in 9 healthy individuals. Five had earlier been proctocolectomized and had ileostomies. Radioactivity was measured in plasma, urine, ileostomy content and feces for a period of 72 h. Radioactivity was present in plasma 15 min after administration. The total recovery of radioactivity was 78-98%, the largest amount being observed in urine during the first 24-hour period. About 20% of the administered radioactive dose was recovered in ileostomy content and 10% in feces. The recovered radioactivity in plasma, urine and extracts of ileostomy content and feces was characterized with dialysis and gel filtration. All radioactivity in plasma and urine corresponded to free 131I, whereas in the extracts radioactivity corresponding to intact enzyme and degradation products as well as a small amount of free 131I was observed. It is concluded that pancreatic trypsin is degraded during intestinal passage as with other proteins. Due to a deiodinating mechanism in the intestine, only free 131I is absorbed into the circulation. This deiodination does not take place in duodenal juice. The absence of high molecular weight radioactivity in plasma argues against an enteropancreatic circulation.
Serum retinol and serum carotene concentrations were determined over a 6-month period in 137 outpatients with Crohn's disease. Serum retinol measurements were within the reference range for all patients at each assessment period, while serum carotene levels were low in about one quarter of the patients. Of the 56 patients who completed 48-hour stool collections, 41% had stool fat values exceeding the reference value. Serum retinol concentrations were not significantly correlated with the serum carotene concentrations, with the 48-hour stool fat content, or with the Crohn's disease activity. In contrast serum retinol concentrations were correlated with the dietary levels of vitamin A. Serum carotene concentrations were inversely correlated with the stool fat content but were not related to Crohn's disease activity or dietary levels of carotene or total vitamin A. Thus: (1) serum retinol concentrations were normal in this moderately large group of patients with Crohn's disease and did not reflect a low dietary vitamin A intake by 34% of the population; (2) serum carotene levels were frequently low in patients with Crohn's disease, possibly due to the presence of steatorrhea, but were not related to low dietary intakes of carotene or to active Crohn's disease, and (3) a low serum level of carotene does not indicate that the patient is at risk of developing vitamin A deficiency.
The effects of proglumide analogue. CR 1392, on pancreatic exocrine secretion were studied in the isolated pancreatic acini and the isolated perfused pancreata of rats. In the isolated acini, CR 1392 caused a parallel rightward shift of the dose-response curve for amylase secretion stimulated by cholecystokinin octapeptide (CCK-8). CR 1392 inhibited maximally stimulated amylase release by CCK-8 (100 pM) in a concentration-dependent manner, with a half maximal inhibition (ID50) at 8.0 +/- 0.6 microM. CR 1409, another proglumide analogue, also caused a concentration-dependent inhibition (ID50: 3.2 +/- 0.4 microM). Although CR 1409 was about 2.5-fold more potent than CR 1392 in inhibiting the stimulated amylase release, 1 mM CR 1409 caused 107.4 +/- 0.9% increase in amylase release, suggesting acinar cell damage. CR 1392 (1 mM) also caused 19.9 +/- 2.3% increase in amylase release, but was less toxic than CR 1409. The antagonism produced by CR 1392 was selective for CCK and had no effect on amylase release stimulated by other receptor secretagogues or by agents bypassing receptors. CR 1392 added 20 min after the CCK-8 stimulation rapidly abolished pancreatic exocrine secretion in both isolated acini and isolated perfused pancreas. Although the inhibitory effect of CR 1392 was fully reversible in the isolated acini, the pancreata perfused with 100 microM CR 1392 for 20 min did not respond to the subsequent stimulation with CCK-8 for more than 20 min. These results indicate that CR 1392 is a potent, competitive, specific and long acting antagonist of CCK in rat pancreas.
A stable isotope labeling (13C and D) was administered to 8 subjects in order to observe the short-term effect of phytosterols (Cytellin 9 g/day) or calcium (calcium gluconate 3 g/day) on the processes involved in cholesterol elimination in the feces. Under control conditions, the mean fraction of fecal cholesterol having a plasmatic origin was 69% and that of cholesterol secreted by the digestive tract 11%. The remaining fraction represented unabsorbed dietary cholesterol. While both treatments reduced the absorption of cholesterol, Cytellin enhanced the fecal excretion of plasma cholesterol and calcium lowered it. The change observed in the rate of intestinal external secretion did not follow the change in the fecal excretion of cholesterol.
The 13C-mixed triglyceride (13C-MTG) breath test (BT) is a safe and noninvasive method to measure exocrine pancreatic function. We examined the reproducibility of the 13C-MTG BT in a group of 17 healthy controls and 8 adult patients with cystic fibrosis (CF). In controls no statistically significant difference in percentage dose recovered (PDR) was found between the first and the second result of repeated tests: the mean values were 35.5 +/- 5.5 vs. 32.3 +/- 7.4 PDR (n = 17). Also in the group of CF patients (n = 8) no significant difference between duplicate tests was found: mean values 17.5 +/- 7.5 and 17.5 +/- 7.8 PDR, respectively. The coefficient of repeatability is 8 PDR for the controls and CF patients together. Two factors might influence the outcome of the test. First, individually measured CO2 excretion instead of the usually assumed 9 mmol/h/kg CO2 production might alter the result of the 13CO2-MTG BT. Therefore CO2 production was measured by indirect calorimetry in 12 healthy controls and 13 CF patients. Measured CO2 excretion was not significantly different between healthy controls and CF patients. Secondly, exercise might influence BT results due to its separate effects on both CO2 production and excretion. The influence of physical exercise at a level of 25 or 50 W was studied on a bicycle ergometer in 4 healthy controls during the last 5 min of each 30-min sampling period. Exercise gave lower test results, on average 85% of the PDR value at rest. Incidently, it was observed in 1 patient that use of 13C-enriched food during the day preceding the test caused inappropriately low test results in the 13C-MTG BT. The 13C-MTG BT is a test with a fair but less than desirable reproducibility. Test conditions should be standardized to eliminate confounding influences. Exercise should be limited or strictly defined. Diet on the day preceding the test should not contain naturally 13C-enriched food. There is no need to measure individual CO2 production.
Many of the reports on the diagnostic efficacy of the 13C-urea breath test (13C-UBT) for the detection of Helicobacter pylori in the residual stomach have shown negative results. We conducted an evaluation to establish a standardized protocol and an appropriate cutoff value for 13C-UBT in partial gastrectomy patients.
Forty-two patients undergoing partial gastrectomy were included. Three gastric biopsies from the anastomotic site and mid-to-high body were taken at panendoscopy for histology, culture and rapid urease test (RUT). The 13C-UBT protocol included ingestion of 100 mg 13C-urea, use of mouthwash, and the body in a horizontal position on the left side. Six breath samples were taken after ingestion.
The Delta 13CO2 values were significantly elevated in infected patients at all time points, and values were higher at 20 min and thereafter than at an earlier time point. The sensitivity of 13C-UBT was 96.3% with the cutoff of 2.0 per thousand at 40 min. The accuracy rates were highest with 13C-UBT, culture, RUT and histological tests, in that order.
Forty minutes and a cutoff of 2.0 per thousand were found to be optimal for the test, with the body position horizontal on the left side. In the present protocol 13C-UBT appears to be a reliable tool with the same accuracy rate as other routine tests in patients with a remnant stomach.
Confirmation of Helicobacter pylori eradication by urea breath test (UBT) is currently performed 4-6 weeks after completion of therapy because of unacceptable false-negative results in UBTs performed earlier. Use of a high-dose citric acid test meal appears to enable accurate detection of H. pylori even during short term therapy with proton pump inhibitors.
To evaluate if use of a high dose citric acid (4.0 g) test meal can decrease the interval required for confirmation of eradication after triple therapy.
233 patients positive for H. pylori were randomized to undergo UBT at 7 days or 14 days after triple therapy, and again at 6 weeks. The latter test was considered the gold standard test.
The UBT performed 6 weeks after the end of treatment found that 79.9% were cured. The same test 7 days after therapy found false-negative detection of H. pylori in 7.3% patients compared to 3.2% patients examined after 14 days. The sensitivity, specificity, positive and negative predictive values and accuracy for evaluation on day 14 were 80, 100, 100, 96.3 and 96.7%, respectively.
High-dose citric acid-based UBT is a valid test for the assessment of H. pylori status 14 days after triple therapy. This may obviate the delay in instituting second-line eradication therapy, or further evaluation of the symptomatic patient unresponsive to therapy despite eradication.
Knowledge is limited regarding the effects of rabeprazole on gastric emptying. This randomized, open, crossover study was undertaken to investigate the effects.
In 24 healthy volunteers (13 men and 11 women, aged 22-53 years), solid emptying was assessed twice using the 13C-octanoate breath test. On one occasion, the subjects received 20 mg rabeprazole for the preceding 2 days and 1 h before the test. On another occasion, they underwent no pretreatment. The time course of cumulative recovery of 13CO2 in breath was fitted to z(t)=m(1-e-kt)beta-1, and regression constants of k and beta were determined. The half 13CO2 excretion time (t(1/2)b)) and the time of maximal excretion (tmax) were calculated. Under the crossover protocol, k and beta can describe the emptying features more precisely; a larger (smaller) beta indicates a slower (faster) emptying in the early phase, and a larger (smaller) k indicates a faster (slower) emptying in the later phase. Between the two occasions, k, beta, t(1/2)b, and tmax were compared.
Rabeprazole significantly decreased k and beta, significantly prolonged t(1/2)b, but tmax remained unchanged.
Rabeprazole has dual effects on solid emptying: an initial acceleration with a subsequent deceleration, resulting in an overall delay.
An experimental procedure using stable isotope-labeled cholesterol (13C and D) was carried out on 15 healthy subjects to distinguish the different origins of neutral fecal sterols in man: nonabsorption of dietary cholesterol, fecal excretion by transfer of plasmatic cholesterol and external secretion of cholesterol biosynthetized in digestive tract and directly eliminated. For a mean daily mass of 652 mg of fecal cholesterol, unabsorbed dietary cholesterol is 20% (133 mg), excreted cholesterol 67% (434 mg) and cholesterol from external secretion 13% (85 mg). A short treatment (4 days) with cholestyramine or different bile acids was then administered to each subject to study the possible variations in their fecal elimination of cholesterol. The more evident effect was the large stimulation of external secretion of cholesterol (234 mg/day) observed after chenodeoxycholic acid feeding (1 g/day). This treatment tends also to decrease dietary cholesterol absorption and to enhance excretion of cholesterol.
In pharmacokinetics, the Wagner-Nelson (W-N) method can accurately estimate the rate of drug absorption from its urinary elimination rate. A stable isotope (13C) breath test attempts to estimate the rate of absorption of 13C, as an index of gastric emptying rate, from the rate of pulmonary elimination of 13CO2. The time-gastric emptying curve determined by the breath test is quite different from that determined by scintigraphy or ultrasonography. In this report, we have shown that the W-N method can adjust the difference.
The W-N equation to estimate gastric emptying from breath data is as follows: the fractional cumulative amount of gastric contents emptied by time t = Abreath (t)/Abreath (infinity) + (1/0.65).d[Abreath (t)/Abreath (infinity) ]/dt, where Abreath (t) = the cumulative recovery of 13CO2 in breath by time t and Abreath ( infinity ) = the ultimate cumulative 13CO2 recovery. The emptying flow curve generated by ultrasonography was compared with that generated by the W-N method-adjusted breath test in 6 volunteers.
The emptying curves by the W-N method were almost identical to those by ultrasound.
The W-N method can generate an accurate emptying flow curve from 13CO2 data, and it can adjust the difference between ultrasonography and the breath test.
Scintigraphy and the 13C-octanoic acid breath test are both applied to assess gastric emptying. Using the 13C-octanoic acid breath test, excretion curves show 13C excretion immediately after ingestion of a solid egg meal, in contrast with scintigraphy where gastric emptying is observed after a lag phase. The aim of our study was to investigate whether transpyloric flow occurs during and directly after meal ingestion. Therefore, transpyloric flow was measured during and after ingestion of an egg meal labeled with 13C-octanoic acid, using Doppler ultrasonography. The breath test was performed simultaneously, with samples taken at regular intervals. The first emptying episode was observed 6.9 (3.9-16.2) min after start of meal ingestion. A significant relation between recovery of 13C and total duration of gastric emptying during the first 20 min was observed (partial correlation coefficient r = 0.80, p < 0.001). In conclusion, transpyloric flow starts during ingestion of a solid egg meal and results in detectable excretion of 13C.
In the choice of reconstructions, digestive and absorptive disturbances, resulting in weight loss after subtotal gastrectomy, remain a problem. The aim of this study was to compare fat absorptive function after Billroth I (B-I) and Roux-en-Y (RY) reconstructions after subtotal gastrectomy for gastric cancer.
A (13)C-labeled mixed triglyceride breath test was performed in 31 patients after subtotal gastrectomy and in 15 healthy volunteers to assess fat digestive and absorptive function. Seventeen B-I reconstructions and 14 RY reconstructions were performed after subtotal gastrectomy. Fat digestive and absorptive function was determined by percent (13)CO(2) cumulative dose at 7 h. Relationship between fat absorptive function and perioperative factors were analyzed.
Gender distribution, mean age, pathological staging, level of lymph node dissection, preservative procedure of the vagus nerve and mean follow-up period in the two surgical groups did not differ significantly. Only the type of reconstruction (p = 0.024) was associated with differences in fat digestive and absorptive function by univariate analysis: B-I reconstruction was superior to RY reconstruction.
Fat digestive and absorptive function after B-I reconstruction was superior to that after RY reconstruction, probably because the B-I reconstruction was the procedure that permitted food passage through the duodenum.
(13)C-hiolein is a purified algal triglyceride which is synthesized with 98% of all carbon atoms of the molecule uniformly (13)C-labeled. Orlistat is the new name for tetrahydrolipstatin (THL), which is a specific and potent inhibitor of gastrointestinal lipases which induces artificial fat malabsorption in humans. The aim of the present study was to use the (13)C-hiolein breath test (HBT) to assess THL-induced fat malabsorption in healthy volunteers.
Eight healthy volunteers of normal body weight underwent 2 study periods of 4 days of diet with or without THL 120 mg t.i.d. On day 5, a HBT was performed. (13)CO(2) recovery in breath samples was measured over 24 h by isotope ratio mass spectrometry.
The peak (13)CO(2) excretion occurred only after 5 h in both treatment groups with little difference during the first 4 h between the groups. THL potently reduced fat digestion and absorption with the most pronounced effect observed after 8 h: 1.1+/-0.2 vs. 2.3+/-0.3% dose in control experiments (p<0.05). The 24-hour cumulative (13)CO(2) excretion was also significantly reduced by THL: 14.9+/-2.2 vs. 28.4+/-4.1% dose in control experiments (p<0.05). In 6 of the 8 subjects, the cumulative (13)CO(2) excretion was lower with THL 120 mg t.i.d. than with placebo.
The HBT well reflects THL-induced artificial fat maldigestion in healthy volunteers.
We have developed a 14C-urea breath test to follow the course of Helicobacter felis infection in mice. Peak 14CO2 production occurred approximately 8 min after substrate administration. The test values were compared to those from a rapid urease test and correlated with the presence of pathogens by histology. The sensitivity was 99%, specificity 91%, positive predictive value 95% and negative predictive value 99% when the assay was conducted in fasted mice. We conclude that in mice the breath test analysis is a useful noninvasive method for detecting the presence of H. felis or for evaluating therapeutic agents affecting growth or survival of the organism.
In previous histochemical studies the distribution of the two Ca(2+)-binding proteins MRP8 and MRP14 as well as their heterocomplex MRP8/14 has been demonstrated in different inflammatory diseases. Monoclonal antibodies against MRP8 and MRP14 and their heterodimer MRP8/14 (27E10 epitope) were used to investigate immunohistochemically the distribution of these proteins in routinely processed small and large bowel tissues from patients with Crohn's disease (CD). Furthermore, we used a sandwich immunoassay to measure serum concentrations of MRPs in 62 patients were simultaneously assessed by the Crohn's disease activity index (CDAI) and the severity activity index of Goebell (SAI). In our immunohistochemical study, MRP8, MRP14 and heterocomplex MRP8/14 were demonstrated in the majority of granulocytes and macrophages in active CD. Additionally, a strong complex MRP8/14 immunoreactivity was present in epithelial cells adjacent to ulcerative and fissuring lesions in the bowel. Serum MRP8/14 concentrations were significantly (p < 0.0001) increased in patients with active CD (CDAI > 150, SAI > 120). No correlations were found for level of MRP14 and MRP8 alone, respectively. The follow-up of individual patients with initially active CD showed a further increase in MRP8/14 levels during acute attacks of the inflammatory process. We suggest that our assay for MRP8/14 discriminates well between active and inactive CD and may have considerable potential in the analysis of clinical disease activity in CD patients. Our morphological results confirm the finding of increased MRP8/14 serum levels in patients with active CD.
Certain CNS-active compounds decrease gastric acid secretion in vivo. In this study a number of tricyclic antipsychotic or antidepressant compounds together with haloperidol, a nontricyclic antipsychotic agent, were shown to inhibit dibutyryl-cAMP-stimulated [14C]aminopyrine uptake, an index of acid secretory activity in a rat isolated gastric mucosal cell preparation. The observed order of potency was: thioridazine greater than chlorpromazine greater than haloperidol approximately equal to desipramine approximately equal to imipramine greater than clozapine. Comparison of these potencies with those of the known (H+ + K+)ATPase inhibitors timoprazole and omeprazole revealed that the potency of timoprazole was similar to the one of clozapine while omeprazole was intermediate between thioridazine and chlorpromazine. Pirenzepine was ineffective.
The effect of age and sex on the N-demethylation rate of 14C-aminopyrine was studied by breath test in 28 normal subjects (12 men, 16 women) aged 26 to 86. It was found that demethylation of aminopyrine was inversely related with age and unaffected by sex. 6 out of 8 patients aged 70 or over, had breath test values within the range of values obtained in 31 patients with alcoholic cirrhosis. In the elderly, a breath test can therefore be considered abnormal only if it is compared with a control group of the same age.
The prognostic value of the intravenous 14C-aminopyrine breath test (ABT) in liver cirrhosis was compared to that of the well-established multiparametric Child-Pugh classification and that of serum bile acids, an endogenous parameter of liver function for which a prognostic value in patients with liver cirrhosis has been demonstrated previously. 84 patients with liver cirrhosis were studied. 32 of the patients died during the observation period. Survival was analyzed for periods of 3, 6 and 12 months after examination. For all chosen observation periods, the Child-Pugh score was of prognostic value. ABT gave prognostic information for periods of 6 and 12 months of survival, but was by far inferior to the Child-Pugh score. Serum bile acids in our population did not yield prognostic information at any time interval studied. We conclude that in our group of cirrhotic patients, the prognostic value of the Child-Pugh classification was by far superior to quantitative liver function tests in predicting survival.
The cholyl glycine-1-14C breath test was evaluated in a variety of gastrointestinal disorders. 138 tests were performed in 106 patients. Methods of data expression were evaluated and the cumulative 8-hour value was used. In 27 control patients the upper limit of the normal was found to be 78. A good correlation was found between the peak values and the cumulative 8-hour values (r = 0.95, p less than 0.01). The reproducibility of the test was good (r = 0.985, p less than 0.05). Abnormal results were found in 12 out of 13 cases with resection of the ileum and 11 out of 14 cases with Crohn's disease of the distal small bowel. The test was normal in cases with diseases of the proximal small bowel (celiac, Whipple's and Chron's diseases). The test was also normal in patients with colitis. It was abnormal in some of the cases after cholecystectomy and in most cases with carcinoma of the pancreas. The breath test was useful in monitoring the results of treatment in bacterial overgrowth of the small bowel. False negative results were observed after antibiotic treatment. The method seems to be more sensitive than the Schilling test in diagnosing disease of the distal small bowel.
18 control subjects and 18 patients, with a variety of gastrointestinal conditions were investigated using a 10-muCi 14C-D-xylose breath test. The latter also underwent quantitative bacterial studies of fluid obtained by intestinal intubation. In 14 patients a smaller dose of 3 muCi 14C-D-xylose was compared to the standard dose and there was a good correlation between the two doses. The peak value of the 14C-D-xylose test provided the best discrimination between patients with and without bacterial overgrowth. The 14C-glycocholic acid test performed in 15 patients, although as sensitive, was less discriminating. The 14C-D-xylose breath test is reliable and more specific in confirming the diagnosis of small intestinal bacterial overgrowth without having to resort to direct bacterial studies.
The effect of a peripheral cholecystokinin (CCK)-receptor antagonist, CR 1409, on pancreatic growth has been studied in the rat. 1.8 nmol/kg CCK-8 or caerulein and 3.6 nmol/kg bombesin or gastrin-releasing peptide (GRP) administered subcutaneously 3 times daily for 4 successive days increased pancreatic weight and its content in protein, enzymes and RNA but not in DNA, suggesting cellular hypertrophy. CR 1409 (10 mg/kg) administered intragastrically 30 min prior to peptides prevented pancreatic growth due to CCK-8 or caerulein but not that induced by bombesin and GRP. It is concluded that bombesin and GRP act on the exocrine pancreas directly rather than through the release of CCK.