bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of endothelin‐1 in repeated electrical stimulation‐induced microcirculatory disturbance and mucosal damage in rat stomach
Authors: FUKUMURA DAI , KUROSE IWAO , MIURA SOICHIRO , SERIZAWA HIROSHI , SEKIZUKA EIICHI , NAGATA HIROSHI , TSUCHIYA MASAHARU , ISHII HIROMASA
Published: March 2008

The aim of the present study was to clarify the involvement of endogenous endothelin in the pathogenesis of gastric mucosal damage. The rat stomach was exposed and repeated electrical stimulation (RES) was applied to the small arterial wall close to the lesser curvature. Significant mucosal haemorrhagic lesions (ulcer and erosion) were noted within 30 min after RES. Intravital microscopic observations revealed that an arteriolar constriction occurred in the submucosal layer of the rat stomach approximately 5 min after the completion of RES. Following the arteriolar constriction, the mucosal blood flow of the rat stomach, which was monitored by using a laser Doppler velocimeter, decreased to approximately 30% of the control value. The plasma immunoreactive endothelin‐1 level in the regional blood of the stomach was significantly increased immediately after RES preceding the decrease in mucosal blood flow. Immunohistochemical studies revealed that endothelin‐1 and big‐endothelin‐1 were detectable in the arteriolar endothelium around the muscularis mucosa, supporting the involvement of endothelin‐1 in RES‐induced mucosal ischaemia. In addition, BQ‐123, a specific antagonist of the endothelin A (ETA) receptor, attenuated the reduction of blood flow and the development of haemorrhagic lesions observed in gastric mucosa subjected to RES. The results of the present study suggest that an excessive production of endothelin‐1 in the arteriolar endothelium leads to microvascular derangements accompanied by haemorrhagic alterations of the gastric mucosa.
Metronidazole resistance: A predictor of failure of Helicobacter pylori eradication by triple therapy
Authors: MIDOLO PD , LAMBERT JR , TURNIDGE J.
Published: March 2008

Triple therapy (bismuth and two antibiotics) will eradicate Helicobacter pylori infection in 70–90% of subjects. Treatment failure has been attributed to patient compliance and antimicrobial drug resistance. The aim of this study was to examine factors influencing the eradication of H. pylori following triple therapy. Thirty seven subjects with H. pylori cultured from antral biopsies were treated with colloidal bismuth subcitrate (120 mg qid for 2 weeks), metronidazole (400 mg tid for 1 week) and amoxycillin (500 mg tid for 1 week). Pretreatment isolates of H. pylori were tested for metronidazole susceptibility by agar dilution according to the National Committee for Clinical Laboratory Standards guidelines. Factors including age, sex, clinical diagnosis and metronidazole resistance were evaluated in relation to H. pylori. The overall metronidazole resistance was 32%. Metronidazole resistant strains were more frequent in females, with a resistance rate of 54%. Helicobacter pylori eradication occurred in 68% of patients with a metronidazole susceptible stain and only 17% of patients with a metronidazole resistant strain (P < 0.03). Helicobacter pylori eradication is dependent upon susceptibility to metronidazole. This data would support the role for routine metronidazole susceptibility testing using appropriate standardized methods when triple therapy is to be considered.
Chronic liver disease in children on long‐term parenteral nutrition
Authors: MISRA SUDIPTA , AMENT MARVIN E , VARGAS JORGE H , SKOFF CHRISTOPHER , REYEN LAURIE , HERZOG FAY
Published: March 2008

Use of long‐term total parenteral nutrition (TPN) is often presumed to be associated with serious hepatic dysfunction. In this retrospective study, we reviewed the complete charts of patients who had received TPN for more than 2.5 years, starting in infancy or childhood, for evidence of liver dysfunction. There were 16 male and 10 female patients with a total of 254.5 patient years on TPN. Seventeen patients have been on TPN since birth or early infancy. Thirteen of 26 patients derive ≥90% of their calorie intake from TPN. Six patients had hepatomegaly; two of them also had splenomegaly. Twenty‐one patients had normal transaminases, nine have had past episodes of raised enzymes ranging from 2.5 to 7.5 times normal. Seventeen patients always had normal bilirubin levels, five had past episodes of hyperbilirubinaemia, while four patients had persistently raised bilirubin levels (range 1.5–20.7 g/dL). Alkaline phosphatase was normal for age in all patients except two. Hepatic synthetic function, as measured by albumin, pre‐albumin levels and prothrombin time, was within the normal range in all patients except one. Liver biopsies were performed in eight patients. Two biopsies showed cirrhosis, one showed chronic active hepatitis (CAH) with cholestasis, two patients had fibrosis, one showed cholestasis and two biopsies were normal. One patient with cirrhosis and one with CAH were positive for hepatitis C antibody. Another asymptomatic patient was positive for hepatitis B. Only the patient with CAH had hepatic decompensation. We conclude that clinical hepatic failure is uncommon in our group of patients on long‐term TPN for 2.5 years or more. Cirrhosis and fibrosis, when found, could not be solely attributed to TPN.
Metabolic bone disease of liver cirrhosis: Is it parallel to the clinical severity of cirrhosis?
Authors: CHEN CHUN‐CHIA , WANG SUN‐SANG , JENG FONG‐SHYA , LEE SHOU‐DONG
Published: March 2008

Metabolic bone disease has long been recognized in chronic liver disease, especially cholestatic or alcoholic liver diseases. The aim of the present study was to investigate the prevalence and severity of osteodystrophy in cirrhotic men and the correlation of its incidence with the clinical severity of cirrhosis in an endemic area of post‐necrotic hepatitis. We measured serum levels of osteocalcin, 25‐hydroxyvitamin D, parathyroid hormone mid‐molecule, calcium and testosterone in 74 cirrhotic men (Child‐Pugh's classification grade A n= 30, B n= 21 and C n= 23) and 16 healthy controls. Standard X‐rays and bone mineral densities of lumbar spine were performed in 30 patients with post‐necrotic cirrhosis and 10 healthy controls. Serum levels of osteocalcin, parathyroid hormone and testosterone were significantly lower in patients with cirrhosis than in controls. Changes paralleling an increased severity of cirrhosis were found in the serum levels of 25–hydroxyvitamin D and testosterone, but not in the serum levels of osteocalcin and parathyroid hormone. The lumbar bone mineral density was significantly lower in patients with post‐necrotic cirrhosis than in controls (0.97 ± 0.13 vs 1.07±0.12 g/cm2, P<0.05) and was correlated with serum 25–hydroxyvitamin D levels (r = 0.467; P<0.005). There was no correlation between the bone mineral density and serum osteocalcin or the clinical severity of cirrhosis. The prevalence of spinal osteoporosis, as defined by a lumbar bone mineral density greater than two standard deviations below the mean value of the controls, was 20% in cirrhotic patients compared with 10% in controls. Two (6.7%) patients (both grade C) had spinal compression fractures compared with none in the control group. In conclusion, serum osteocalcin and lumbar bone mineral density were significantly lower in cirrhotic men than in controls. However, they were not correlated with each other or the clinical severity of cirrhosis.
Primary sclerosing cholangitis: An experience from India
Authors: KOCHHAR RAKESH , GOENKA MAHESH K , DAS KINSUK , NAGI BIRENDER , BHASIN DEEPAK K , CHAWLA YOGESH K , VAIPHEI KIM , SINGH KARTAR , DILAWARI JANG B
Published: March 2008

Primary sclerosing cholangitis (PSC) is considered to be rare in India. The aim of the present study was to investigate the incidence, clinical profile and outcome of PSC seen in a tertiary care centre. Over a period of 10 years (July, 1984‐June, 1994) 18 patients of PSC were diagnosed at cholangiography (14 patients by endoscopic retrograde cholangiopancreatography, two patients by percutaneous transhepatic cholangiography and two patients by both methods). The presence of secondary causes, such as choledocholithiasis, biliary tract surgery, congenital biliary tract anomalies, cholangiocarcinoma and pancreatic diseases, were excluded. These patients were evaluated retrospectively with respect to their clinical presentation, radiological findings, presence of associated idiopathic ulcerative colitis (IUC), treatment instituted and outcome. The mean (±s.d.) age at diagnosis of PSC was 39.0 (±16.1) years with a male: female ratio of 1.57:1. Nine (50%) patients had associated IUC. The diagnosis of IUC preceded that of PSC in all but one case. Fifteen (83.3%) patients had cholestatic jaundice at presentation, while three (16.7%) patients had asymptomatic rise of alkaline phosphatase. Three (16.7%) patients had recurrent cholangitis and five (27.8%) patients developed portal hypertension during the course of the disease. At cholangiography, intrahepatic radicles were involved in all and extrahepatic radicles in 12 (66.6%) cases. Patients were managed with steroids (n= 7), colchicine (n= 3), ursodeoxycholic acid (UDCA; n= 2) and methotrexate (n= 1), along with symptomatic measures. Mean duration of follow up available in 11 (61%) patients was 20.1 months (range: 1 month‐8 years). Four (36.4%) patients died. Steroids and colchicine did not have any effect while the one patient on UDCA and one on methotrexate showed improvement. In conclusion, in India PSC does not seem to be a rare entity. Its clinical profile and outcome are somewhat similar to those seen in Western countries.
Clinical significance of serum hyaluronan in patients with chronic viral liver disease
Authors: MURAWAKI YOSHIKAZU , IKUTA YUJIRO , KODA MASAHIKO , NISHIMURA YUUKO , KAWASAKI HIRONAKA
Published: March 2008

In order to elucidate the clinical significance of serum hyaluronan in chronic viral hepatitis, serum hyaluronan concentrations were measured using a sandwich enzyme binding assay in 115 patients with chronic viral hepatitis. These findings were examined in relation to the results of laboratory liver tests, levels of serum markers for fibrosis and liver histological findings. Serum hyaluronan levels increased with the progress of liver disease, particularly in liver cirrhosis. There were no significant differences in serum hyaluronan levels among the cirrhotic patients according to Child's grade. Multivariate analysis showed that the significant independent predictors of serum hyaluronan were serum aspartate aminotransferase (P= 0.020), serum alanine aminotransferase (P= 0.008), serum cholinesterase (P< 0.001), particularly serum type IV collagen 7S domain (P< 0.0001), and the histological degree of liver fibrosis (P< 0.0001). These findings suggest that elevated serum hyaluronan levels are closely related to the severity of liver fibrosis. We assessed the predictive value of serum hyaluronan in differentiating cirrhosis from chronic hepatitis, constructing receiver operating curves; we found that serum hyaluronan was a better test for diagnosing cirrhosis than serum type IV collagen 7S domain and laboratory liver tests.
Distribution of peptide‐containing nerve fibres in achalasia of the oesophagus
Authors: WATTCHOW DAVID A , COSTA MARCELLO
Published: March 2008

In this study the innervation of the normal human oesophagus was compared with samples taken from 12 patients undergoing Heller's cardiomyotomy for achalasia. The distribution of all nerve fibres in the oesophageal wall was revealed by immunoreactivity to neuron specific enolase and subpopulations of nerve fibres were revealed by immunoreactivity to vasoactive intestinal peptide, neuropeptide Y, enkephalin and substance P. In healthy oesophagus, many nerve fibres immunoreactive for vasoactive intestinal peptide and neuropeptide Y were present in the circular and longitudinal muscle layers of the oesophageal wall and in the cardia of the stomach, whereas fibres immunoreactive for enkephalin and substance P were uncommon. Neuropeptide Y‐reactive fibres were commonly seen around blood vessels. In the myenteric plexus cell bodies reactive for vasoactive intestinal peptide and neuropeptide Y were prevalent, as were varicose and non‐varicose fibres. In contrast, samples from patients with achalasia revealed few nerve fibres immunoreactive for vasoactive intestinal peptide or neuropeptide Y in either circular or longitudinal muscle, suggesting damage to the inhibitory motor neurons to the muscle layers. Very few fibres were found that were reactive for neuron‐specific enolase, indicating that other fibre populations (e.g. excitatory cholinergic motor neurons) are also damaged in achalasia. These abnormalities were observed in biopsies from both the constricted and dilated portions of the oesophagus, but the pattern of innervation in the gastric cardia was normal. Myenteric ganglion cells were seen in the oesophagus in only two patients and varicose nerve fibres in the myenteric plexus were uncommon. Neuropeptide Y‐reactive perivascular nerve fibres were still found in achalasia as well as non‐varicose nerve fibres in the myenteric plexus. These findings indicate damage to all intrinsic neurons in the oesophageal wall in achalasia; however, extrinsic nerve fibres appear to be intact.
Detection of duodenal fluid in the oesophagus with a sodium ion selective electrode*
Authors: WATSON DAVID I , SMYTHE ANNE , MANGNALL YVONNE F , JOHNSON ALAN G
Published: March 2008

The assessment of duodeno‐oesophageal reflux is difficult as, until recently, no technique has been readily available for continuous ambulatory monitoring. A sodium ion selective electrode placed in the stomach has been previously shown to detect duodenogastric reflux by using sodium as a marker. This relies on the difference in sodium concentration between gastric (5–60 mmol/L) and duodenal, biliary and pancreatic (150 mmol/L) fluids. In this pilot study to assess the efficacy of the electrode in the distal oesophagus, eight subjects without symptomatic gastro‐oesophageal reflux and eight subjects with known duodenogastric reflux were studied. Thirty millilitre volumes of varying sodium solutions (40, 80, 100 and 140 mmol/L) were swallowed to assess the response of the electrode to sodium ions. In both groups, this revealed a constant and reproducible rise in response with increasing concentration (P< 0.0001). The stomachs of subjects with duodenogastric reflux were aspirated via a nasogastric tube to obtain 12 different samples of gastric fluid. This was assayed for sodium and bile acid concentration. The fluid was then reinfused as a 30 mL bolus into the oesophagus through a tube to simulate oesophageal reflux. A rise equivalent to 40–72 mmol/L Na+ was recorded by the electrode in response to samples that contained 58–81 mmol/L Na+ and 0.4–16 mmol/L bile acids, recorded by quantitative analysis, and a response of up to 20 mmol/L Na+ was recorded by the electrode to sodium concentrations < 49 mmol/L and bile acid concentrations of 0.005–0.6 mmol/L. The response was appropriate to the assayed bile acid concentration in all but one sample. The sodium ion selective electrode responds to bile containing fluids introduced into the oesophagus. Further investigation is warranted to determine its ability to measure duodeno‐oesophageal reflux continuously.
The Cathlocator: A novel non‐radiological method for the localization of enteral tubes
Authors: WILLIAMS AJK , FRASER R , CHORLEY DP , DENT J
Published: March 2008

Safe placement of nasogastric tubes requires reliable positioning of the tip of the tube within the stomach. Radiology and aspiration are currently used to confirm tube position, but suffer from significant problems of cost and efficacy, respectively. We have developed a novel method to locate the position of a catheter tip within the body, using the detection of a low energy electromagnetic field generated in a coil located in the catheter with an external hand‐held unit (Cathlocator). In vitro, the unit detected the distance of the coil from the detector with an accuracy of 0.1 cm over a range of 4–12 cm. In vivo studies were performed in 11 healthy volunteers using a purpose‐built manometric assembly that incorporated the signal generating coil in its tip. In all subjects the Cathlocator showed the position of the signal generating coil to be cranial to the xiphisternum when manometric and transmucosal potential difference criteria showed it to be located above the lower oesophageal sphincter. When the coil was within the stomach, the Cathlocator identified its position within the epigastric, umbilical and left hypochondrial regions of the abdomen. The distance of the coil from the surface was significantly greater when in the duodenum mean (±s.e.m. 7.6±0.3 cm; P<0.001) and oesophagus (8.6±0.2 cm; P<0.002) than the stomach (5.0±0.4 cm). In one subject studied twice there was a close correlation between the location and depth measured by the device on each occasion. The Cathlocator is a novel non‐radiological device that has the potential to be useful in the placement of gastrointestinal catheters.
An assembled electrogastrographic device to examine the meal effect on gastric slow wave
Authors: CHANG F‐Y , LEE C‐T , LEE S‐D , JANG H‐C , TSAI D‐S , FU S‐E
Published: March 2008

We have assembled an electrogastrographic device based on the main components of amplifiers, a band‐pass filter, an analogue/digital converter, low band‐pass digital filters and a personal computer. The analysis software uses autoregressive moving average modelling to compute the frequency of slow waves and uses fast Fourier transformation for power spectral computation. Twenty healthy young male volunteers were enrolled in the study to test meal‐elicited responses of the slow wave. Subjects underwent a 15 min recording while fasting and then a standard breakfast, which included 250 mL milk and a cake with a total of 1.45 kj, was ingested within 5 min. The post‐prandial 15 min recording was immediately resumed after the meal. A slight but significant increase in the frequency of slow waves was seen in post‐prandial measurements (mean ± s.d., 0.0506±0.0005 vs 0.0497±0.0005 Hz; P<0.0001). Moreover, a significant enhancement of the power of slow waves was elicited following the meal (36.0±3.1 vs 27.6±3.1 dB; P<0.0001). We conclude that this assembled electrogastrographic device is a reliable means of monitoring gastric myoelectrical activity because the phenomenon of post‐prandial responses of slow waves in either frequency or power is well demonstrated.
Case report: Recurrent hyperammonaemic encephalopathy due to citrullinaemia in a 52 year old man
Authors: CHOW WC , NG HS , TAN† IK , THUM TY
Published: March 2008

The present report describes a Chinese male who presented for the first time with recurrent encephalopathy and hyperammonaemia at the age of 52 years. He was found to have citrullinaemia. To our knowledge, this is the first Chinese with citrullinaemia and the first non‐Japanese who has the variant form of presentation. The patient also has the longest asymptomatic period for citruliinaemia so far described. The patient's biochemical derangement, clinical features and the postulation of his late presentation are discussed. It is noteworthy that simple therapeutic measures, such as lactulose and dietary protein restriction, controlled his symptoms well.
Serum hyaluronic acid reflects the effect of interferon treatment on hepatic fibrosis in patients with chronic hepatitis C
Authors: YAMADA MASAHIKO , FUKUDA YOSHIHIDE , KOYAMA YASUO , NAKANO ISAO , URANO FUMIHIRO , KATANO YOSHIAKI , HAYAKAWA TETSUO
Published: March 2008

Changes in serum hyaluronic acid (HA) in 35 patients treated with interferon (IFN) were studied and the histological change in fibrosis was analysed. Serum HA levels and hepatitis C virus (HCV) RNA were followed from the start of therapy to 12 months after completion of treatment. Histological changes in pre‐ and post‐treatment liver biopsies were assessed using a modified Knodell's scoring system. The serum levels of HA (r = 0.79; P<0.0001) correlated with the degree of fibrosis more closely than with that of amino terminal peptides of type III procollagen (PIIIP; r = 0.45; P<0.05) or type IV collagen (IV‐C; r = 0.42; P<0.05). Only complete responders (CR) had a significant decrease in serum levels of HA and IV‐C (P<0.05), in parallel with histological improvement (P<0.01). Neither partial responders (PR) nor non‐responders (NR) had significant changes in histological scores and in serum levels of fibrotic markers. Significant differences were observed between CR and NR, both in HA levels (P<0.01) and PIIIP levels (P<0.05) 12 months after the cessation of treatment. These results suggest that serum HA is an indicator of the extent of fibrosis in chronic hepatitis C. Serial determinations of serum HA levels may be of use for monitoring the histological response of hepatic fibrosis to IFN treatment in chronic hepatitis C.
Premedication with cyclosporine and perindopril modifies the ischaemia‐reperfusion injury during liver resection in rats
Authors: HARDY KJ , TANCHEROEN S , SHULKES A
Published: March 2008

The aim of the present study was to determine whether pretreatment with cyclosporine (CsA), or perindopril (an angiotensin converting enzyme inhibitor) would modify the ischaemia‐reperfusion injury of vascular occlusion during liver resection. Rats were allocated to four groups (n= 20 for each group): (i) sham operated; (ii) liver resection only; (iii) CsA (15 mg/kg); and (iv) perindopril (4 mg/kg during the three days before ischaemia‐reperfusion injury with liver resection). The ischaemia was produced by a 30 min continuous occlusion. The model was designed to study liver function tests as the principal parameter. Compared with liver resection only, bilirubin was significantly lower with perindopril on days 8 and 23, but significantly higher with CsA on days 1 and 2. The alanine aminotransferase peak (day 1) was significantly lower with both perindopril and CsA. The prothrombin time was significantly less on days 2 and 4 with perindopril and day 4 with CsA. Liver histological changes were minimal in all groups at 30 min ischaemia, but were significantly less severe in the perindopril group. There was a significant decrease in the weight of the regenerated liver at day 23 with perindopril and a significantly lower drop in weight on day 1 and the rate of gain was significantly greater. Perindopril (4 mg/kg) and CsA (15 mg/kg) significantly alter liver function tests, liver histology and bodyweight following an ischaemia‐reperfusion injury associated with liver resection. These findings could limit ischaemia‐reperfusion injury for major liver resections in the clinical setting.
Potentiation of carbon tetrachloride‐induced liver damage by dibutylyl‐3′,5′‐cyclic AMP in unstarved rats
Authors: IRITA KAZUO , OKABE HIRONAO , YAMAKAWA MASAE , YOSHITAKE JUN‐ICHI , TAKAHASHI SHOSUKE
Published: March 2008

It has been reported that carbon tetrachloride‐induced liver damage is potentiated by starvation partly due to fat accumulation in the liver and a decrease in hepatic reduced glutathione concentration and that dibutylyl‐3′,5′‐cyclic AMP (DBcAMP) affects fuel metabolism and decreases hepatic reduced glutathione. We investigated the effects of DBcAMP on carbon tetrachloride‐induced liver damage both in unstarved and starved rats. In unstarved rats, intraperitoneal administration of DBcAMP potentiated an increase in serum alanine aminotransferase activity and fatty vacuolization in the liver, both of which were induced by carbon tetrachloride. Hepatic reduced glutathione concentration was also reduced by DBcAMP, although the change was not significant. In contrast, the administration of DBcAMP in starved rats did not affect carbon tetrachloride‐induced changes in serum alanine aminotransferase activity, histological alterations and hepatic reduced glutathione concentration. Administration of DBcAMP to control rats induced different responses in unstarved control rats compared with starved control rats: in unstarved rats, blood glucose concentration decreased but serum free fatty acid concentration increased, whereas in starved rats, blood glucose concentration increased and serum free fatty acid concentration decreased. It was suggested that DBcAMP potentiated carbon tetrachloride‐induced liver damage in unstarved rats, probably due to hepatic fat accumulation and a decreased hepatic reduced glutathione concentration. The former could increase the affinity of the liver for carbon tetrachloride and the latter could accelerate carbon tetrachloride‐induced lipid peroxidation. It was also suggested that DBcAMP failed to affect carbon tetrachloride‐induced liver damage in starved rats, probably because starvation had already decreased hepatic glutathione concentration and DBcAMP had different effects on fuel metabolism compared with effects observed in unstarved rats.
Microvascular disturbances in the colonic mucosa in antibiotic‐associated haemorrhagic colitis: Involvement of platelet aggregation
Authors: YONEI YOSHIKAZU , YOSHIZAKI YOSUKE , TSUKADA NOBUHIRO , INAGAKI YASUTAKA , MIYAMOTO KEI , SUZUKI OSAMU , KIRYU YASUYOSHI , HIBI TOSHIFUMI , ODA MASAYA , ISHII HIROMASA
Published: March 2008

An ultrastructural study of the colonic mucosa was performed in four patients with antibiotic‐associated haemorrhagic colitis and new findings are reported. Colonoscopy was performed and biopsy specimens were obtained within 24 h of the onset of bloody diarrhoea. Colonoscopy demonstrated diffuse oedematous and haemorrhagic mucosa with erosions and white coat. Light microscopy revealed mucosal haemorrhage and inflammatory cell infiltration. Ultrastructurally, platelet aggregation was frequently present in the lumina of colonic mucosal capillaries, causing engorgement of red blood cells in adjacent microvessels. Mild to severe damage was observed in capillary endothelial cells, including discontinuity of basement membranes, gaps between endothelial cells and the destruction of capillaries. There was no evidence of microvascular spasm. In conclusion, our findings suggest that antibiotics directly or indirectly cause microcirculatory disturbances, which result in tissue damage and haemorrhage, in the colonic mucosa.
Case report: Hippocratic digital and Crohn's disease
Authors: MAKIYAMA KAZUYA , ISHIDA KAZUO , ZEA‐IRIARTE WALTER , ITSUNO MINORU , YAMAKAWA MASAKI , MORI NORIHIKO
Published: March 2008

A case of Hippocratic digital associated with secondary hypertrophic osteoarthropathy complicating Crohn's disease in a 29 year old Japanese male is reported. Hippocratic digital, or finger clubbing, complicating inflammatory bowel disease has been frequently reported in the Western hemisphere. However, its association with secondary hypertrophic osteoarthropathy has been very rarely found in that disease. In Japan, Hippocratic digital has not been described previously. With regard to the pathogenesis of Hippocratic digital and secondary hypertrophic osteoarthropathy, the theory that both entities belong to the same pathological spectrum and that megakaryocytes or platelet clumps may play the most important role, is discussed.
Inhibition of colon cancer precursors in the rat by sulindac sulphone is not dependent on inhibition of prostaglandin synthesis
Authors: CHARALAMBOUS DORA , O'BRIEN PAUL E
Published: March 2008

The non‐steroidal anti‐inflammatory drug, sulindac, inhibits the growth of colorectal tumours in animal models of colon cancer and causes regression of polyps in patients with familial adenomatous polyposis. The mechanism by which sulindac exerts this inhibitory effect is not known, but it has been postulated to be via the inhibition of prostaglandin synthesis. However, two recent studies have indicated that sulindac sulphone, the non‐prostaglandin inhibiting metabolite of sulindac, may be important in tumour inhibition. In the present study, we examined the effect of sulindac sulphone on the formation of aberrant crypt foci, the earliest identifiable lesions in the development of colorectal cancer, in the rat colon. We have previously shown that sulindac causes a dose dependent inhibition of aberrant crypt formation in this model. Aberrant crypt foci were induced with two oral doses of 1,2–dimethyl hydrazine at 25 mg/kg per dose. Treatment with sulindac sulphone at either 10 mg/kg b.d., or 20 mg/kg, b.d., was started on the day following administration of the first carcinogen dose and was continued for 3 weeks. Colons were then removed and examined for aberrant crypt foci. Colonic crypts were visualized by staining the unsectioned colon in 0.2% methylene blue solution. There was a significant reduction in the number of aberrant foci in rats treated with sulindac sulphone at 20 mg/kg, b.d. (ANOVA, P= 0.0054). The mechanism by which non‐steroidal anti‐inflammatory drugs inhibit formation of aberrant crypt foci is not clear; however, these data suggest that it is not due to the inhibition of prostaglandin synthesis.
Increased urinary endothelin excretion in patients with liver cirrhosis
Authors: KITANO MASAYUKI , UEMASU JIRO , KAWASAKI HIRONAKA
Published: March 2008

The urinary endothelin level in patients with chronic liver disease was determined in order to explore its possible involvement in renal function. The plasma endothelin level was significantly higher in patients with liver cirrhosis (LC) than in those with chronic hepatitis (CH) or in control patients (C). Similarly, urinary endothelin excretion in LC was significantly increased, compared with CH and C. Urinary endothelin demonstrated a significant positive correlation with creatinine clearance. The ratio of endothelin clearance/creatinine clearance did not differ statistically among the three groups. Urinary sodium excretion in LC was positively correlated with plasma endothelin, but not with urinary endothelin. Urinary endothelin excretion demonstrated a significant negative correlation with urinary kallikrein in LC. The present data suggest that increased urinary endothelin excretion in cirrhotic patients primarily depends upon elevated plasma levels of endothelin, but not renal production. Also, a possible link between endothelin and the kallikrein‐kinin system in liver cirrhosis is indicated.
Gastric mucosal energy metabolism and intracellular mucin content changes in patients with liver cirrhosis
Authors: KAWANO SUNAO , TANIMURA HIROHISA , TSUJI SHINGO , TAKEI YOSHIYUKI , NAGANO KOUICHI , KASHIWAGI TORU , FUSAMOTO HIDEYUKI , KAMADA TAKENOBU
Published: March 2008

Biopsy samples from patients with liver cirrhosis were investigated for changes in gastric mucosal energy metabolism and intracellular mucin content using high performance liquid chromatography and an image analysing system. The test group consisted of eight non‐cirrhotic patients with endoscopically normal mucosa (controls) and eight cirrhotic patients with oesophageal varices. The amount of ATP, energy charge level and intracellular mucin content were all significantly decreased in cirrhotic patients when compared with those of the controls. The decrease in energy charge also correlated well with the decrease in intracellular mucin content in the gastric mucosa. The results indicate that gastric mucosal energy metabolism is impaired in cirrhotic patients concomitantly with a decrease in the intracellular mucin content in the gastric mucosa. These changes may weaken defensive mechanisms against acid and NSAID, resulting in gastric mucosal injury in cirrhotic patients.
Effect of verapamil on renal haemodynamics in a portal hypertensive rat model
Authors: LAY CHII‐SHYAN , YANG MAY CHUEN‐MAY , WU SUE‐LIN , TSAI YANG‐TE , WU KUO‐LIANG , CHIEN SHU
Published: March 2008

In order to investigate the effects of verapamil on renal haemodynamics in rats with portal hypertension, verapamil was given at either a low (0.2 mg/kg) or high (2 mg/kg) dose to rats after portal vein ligation. An approximate 12% decrease in mean arterial pressure followed administration of low dose verapamil, with a significant decrease in cardiac output and renal blood flow, as well as reduced portal pressure, observed; these signs were all indicative of a rise in renal vascular resistance. In contrast, the marked fall in both mean arterial pressure and cardiac output with high dose verapamil, accompanied by a significant decrease in portal pressure and no change in renal blood flow, suggests a reduction in renal vascular resistance. This study shows that the acute effects of verapamil on renal haemodynamics may vary with the dose used. Also, acute verapamil administration tends to decrease renal blood flow to alter the autoregulation of the kidney; thus, caution should be taken in the clinical use of verapamil in the treatment of cirrhosis with portal hypertension.
Idiopathic adulthood ductopenia
Authors: NAKANO ISAO , FUKUDA YOSHIHIDE , KOYAMA YASUO , URANO FUMIHIRO , YAMADA MASAHIKO , KATANO YOSHIAKI , MARUI AKIKO , IMADA KAZUMI , HAYAKAWA TETSUO , ITO MASAFUMI , YAMASHITA YORIKO , IMOTO MASAMI , NAKANUMA YASUNI
Published: March 2008

In 1981, a 26 year old man occasionally demonstrated elevated serum transaminase concentrations. He had no history of medication, or a personal or family history of jaundice, except for prolonged physiological jaundice as a neonate. Serum hepatitis B surface antigen, hepatitis C virus antibody and anti‐mitochondrial antibody were absent. A wedge biopsy specimen revealed ductular proliferation, mild inflammation of the portal area and disappearance of bile ducts from 80% of the portal tracts. Serial sections demonstrated a vanishing bile duct. Endoscopic retrograde choledo‐chopancreatography, portography and arteriography demonstrated no abnormalities. In 1994, the patient died of hepatic failure following a 12 year observation period. He was subsequently diagnosed with idiopathic adulthood ductopenia on the basis of the criteria proposed by Ludwig.
Effect of cisapride on functional dyspepsia in patients with and without histological gastritis: A double‐blind placebo‐controlled trial
Authors: YEOH KG , KANG JY , TAY HH , GWEE KA , TAN CC , WEE A , TEH M , CHOO HF , CHINTANA‐WILDE W
Published: March 2008

In the present double‐blind placebo‐controlled study the effect of cisapride on functional dyspepsia was evaluated in patients with and without histological gastritis. Patients with functional dyspepsia and whose symptoms persisted after a 2 week run‐in period with antacid treatment were randomized to receive cisapride (10 mg) or matching placebo three times daily for 4 weeks. Symptoms of epigastric pain, bloating, nausea, belching, early satiety and heartburn were graded on a four‐point scale based on patients’ feedback and diary card recording. A global response was also formulated by the investigators. One hundred and four patients entered the study and 76 completed the trial, comprising 36 patients with histological gastritis and 40 patients without gastritis. Symptom scores in both gastritis and non‐gastritis groups were significantly improved by both cisapride and placebo; however, the improvement was not statistically different between the two treatment groups. Cisapride produced a good or better global response in 58% of subjects with histological gastritis and in 53% of subjects without gastritis compared with 47% and 52%, respectively, of patients on placebo; this difference was not statistically significant. Gastric histology did not influence the effect of cisapride on the symptoms of functional dyspepsia.
Tungstic acid reduction of cold‐resistant stress‐induced ulceration in rats
Authors: QIU BS , PFEIFFER CJ , WU W , CHO CH
Published: March 2008

Sprague‐Dawley rats were restrained at 4°C for 2 h (stress). Tungstic acid in a single dose of 0.01, 0.1, 1, 10, 100 or 300 mg/kg (dissolved in distilled water) was administered intragastrically to animals 30 min prior to stress. Stress induced significant gastric mucosal damage, whereas tungstic acid pretreatment dose‐dependently reduced lesion formation. Doses of tungstic acid of 1 mg/kg and higher significantly (P < 0.05–0.001) decreased ulcers. The mucosal mast cell counts in rats pretreated with tungstic acid were significantly higher than those of control rats. In motility experiments using oral administration of amberlite pellets, pretreatment with tungstic acid dose‐dependently reduced the gastric emptying rate during a 1 h period of stress. Gastric mucosal xanthine oxidase and superoxide dismutase (SOD) activities, after pretreatment with a single dose of tungstic acid, were not altered in stressed animals. It is suggested that tungstic acid effectively antagonizes stress‐induced gastric ulcers, possibly by decreasing motility and mass cell degranulation. Xanthine oxidase and SOD activities and mucous content were not changed in the gastric mucosa by the present method of tungstic acid administration.
A controlled trial comparing the efficacy of rice‐based and hypotonic glucose oral rehydration solutions in infants and young children with gastroenteritis
Authors: WALL CR , SWANSON CE , CLEGHORN GJ
Published: March 2008

A prospective randomized trial was conducted to compare the efficacy of a rice‐based oral rehydration solution (ORS) with glucose ORS in infants and children under 5 years of age with acute diarrhoea and mild to moderate dehydration (< 10%). One hundred children presenting to a large metropolitan teaching hospital were eligible for entry to the study and were randomized to receive rice ORS or glucose ORS. Outcome measures were stool output (SO), duration of illness (DD) and recovery time to introduction of other fluids (RTF) and diet (RTD). Significant differences were found for all outcome measures in favour of the rice ORS group. Mean SO was lower (160 vs 213 mL; P < 0.02), mean DD was reduced (17.3 vs 24.3 h; P = 0.03) and median RTF was decreased (12.7 vs 18.1 h; P < 0.001) in the rice ORS group compared with the glucose ORS group. The median time to introduction of diet and mean length of hospital stay showed similar significant reductions. Our study has shown rice ORS to be an acceptable alternative to glucose ORS in young children and have shown that it is significantly more effective in reducing the course of diarrhoeal illness and the time taken to return to normal drinking and eating habits.
Effect of quinolone antibiotics on hepatic growth and protein synthesis following partial hepatectomy in rats
Authors: MINUK GY , ASSY N , DING LX , GAUTHIER T , PASHNIAK DD
Published: March 2008

Quinolone antibiotics inhibit eukaryotic as well as prokaryotic cell growth and protein synthesis. To determine whether these properties adversely affect hepatic growth and recovery following surgical resection, five groups of healthy, adult male rats (n = 7–8/group) were treated for 10 days with equal volumes of either ofloxacin (50 mg/kg), fleroxacin (25mg/kg), ciprofloxacin (25 mg/kg), norfloxacin (15mg/kg) or sterile saline (controls) prior to 70% partial hepatectomy (PH) and daily thereafter until death. Restituted liver mass, DNA and protein synthesis rates were determined at 24, 48 and 72 h PH. The results of the study revealed that all parameters of hepatic regeneration were similar in the five study groups at each time interval. To ensure that an effect on hepatic regeneration was not dose‐dependent, additional experiments were performed where 1, 10 and 100 mg/kg ciprofloxacin was administered and DNA synthesis was measured 24 h post‐PH. Once again, the results were similar to sterile saline‐treated controls. These findings suggest that the quinolone antibiotics are unlikely to have an adverse effect on hepatic recovery following surgical resection of the liver and are safe to use in that setting.
Antibodies to hepatitis C virus and elevated transaminase levels in a town of hyperendemicity in Iwate, Japan
Authors: KOYAMA TOMIKO , TSUDA FUMIO , ISHIKAWA KAZUYOSHI , OISHI HIROSHI , TAZAWA MINORU , YOSHIZAWA HIROSHI , SATO SHUNICHI , OKAMOTO HIROAKI
Published: March 2008

In an annual survey for liver function tests in persons aged > xs35 years in Iwate Prefecture, Japan, a town was identified where high levels of alanine aminotransferase abounded. Of 5152 inhabitants aged > 35 years in this town, antibodies to hepatitis C virus (HCV) determined by enzyme‐linked immunosorbent assay with HCV core peptides were detected in 798 (15.5%) people, hepatitis B surface antigen was detected in 47 (0.9%) people and antibodies to hepatitis B surface antigen and/or hepatitis B core antigen unaccompanied by surface antigenaemia were detected in 1748 (33.9%) people. Antibodies to HCV core peptides correlated closely with the antibodies detected by passive haem‐agglutination with recombinant HCV proteins of the second generation. Antibodies to HCV core peptides were particularly common in one of the nine districts of the town (district 8), where 276 (45.3%) of 609 inhabitants tested positive; there were no differences in the frequency of serological markers of hepatitis B virus (HEV) infection among residents in the nine districts. Of the 798 individuals with antibodies to HCV core peptides, 257 (32.2%) were found to have elevated transaminase levels. A history of transfusion was associated with a high frequency of antibodies to HCV core peptides, except in district 8 where such antibodies were equally frequent in residents irrespective of transfusions. These results indicate an epidemiology of HCV distinct from that of HBV in this town and a very local spread of HCV, as well as a high frequency of hepatic injuries in individuals with antibodies to HCV.
Infra‐red (ATR/FT) spectroscopic study on the conformational structure of the isolated human gastric mucus pretreated with ethanol
Authors: LIN SHAN‐YANG , WU CHEW‐WUN , LI MAY‐JANE , LIANG RUN‐CHU
Published: March 2008

In order to investigate the conformational structure of isolated human gastric mucus gel pretreated with or without ethanol, gel samples were determined by attenuated total reflection/Fourier transform‐infra‐red (ATR/FT‐IR) microspectroscopy. The result indicates that the secondary structure‐dependent amide I band and the glycoprotein region were significantly different in the gastric mucus gels pretreated with and without 40% ethanol. The structural composition of β‐sheet structure (1640‐1600 cm−1) increased from 38.48 to 55.08% (+16.6%) after 6‐hour pretreatment with 40% ethanol, but the β‐turn structure, (1660‐1700 cm−1) decreased from 41.38 to 24.29% (‐17.05%). The peak area ranging from 1180 to 1000 cm−1, assigned to the glycoprotein region, was also different after pretreatment with ethanol for 6 h. The higher peak area of the carbohydrate band was obtained in the frequency region between 1000 and 1040 cm−1 and 1100 and 1180 cm−1 for mucus gel pretreated with 40% ethanol. However, the peak area ranging from 1100 to 1040 cm−1 mainly due to the symmetric phosphate stretching mode of proteins was somewhat lower for the ethanol‐pretreated mucus gel than the native mucus gel. This result strongly reveals that ethanol significantly modified the conformational structure of proteins and carbohydrates of gastric mucus gel. We propose that the dehydration and interference of hydrophobic interactions in the isolated mucus gel after pretreatment with ethanol might be responsible for this conformational change.
A quantitative assessment of serum chylomicron by light scattering intensity: Application to the intestinal fat absorption test
Authors: TAZUMA SUSUMU , MIURA HIROYUKI , HIRANO NAOMICHI , HATTORI YOSHIHIRO , KAJIHARA TSUYOSHI , TSUCHIMOTO DENYA , MIYAKE HIROAKI , NISHIOKA TOMOJI , HYOGO HIDEYUKI , NAKAO SEIJI , YAMASHITA GUNJI , KAJIYAMA GORO
Published: March 2008

A novel fat absorption test to clarify the malabsorption syndrome was developed using a micronephelometric technique and compared with the classic conventional technique using 131I‐triolein. An integrity of time‐sequential light scattered from chylomicron‐related turbidity in serum was determined between 0 and 300 min after butter fat load, being expressed in terms of the light scattering intensity (LSI). A good correlation was obtained between LSI and the serum level of chylomicron‐triglyceride determined by an ultracentrifugation technique (r=0.819, P < 0.001). The maximal LSI was consistently observed at 180 min after administration of a test meal in the normal group (n= 39), whereas the malabsorption syndrome group (n= 35) was distinctly different and could be further classified according to four patterns of LSI changes. In addition, an inverse correlation was found between this fat absorption test and the 131I‐triolein absorption test. It was concluded that the micronephelometric technique which does not use a radionuclide is advantageous in its simple and safe evaluation of fat malabsorption syndrome.
GB virus‐C infection among chronic haemodialysis patients: Clinical implications
Authors: OKUDA KUNIO , KANDA TATSUO , YOKOSUKA OSAMU , HAYASHI HARUYUKI , YOKOZEKI KAZUO , OHTAKE YOSHIO , IRIE YASUBUMI
Published: March 2008

It is known that patients on chronic haemodialysis are frequently infected with hepatitis C virus (HCV). It has recently been found that GB virus‐C (GBV‐C) and hepatitis G virus frequently coinfect patients with HCV. This study aimed at elucidating the clinical implications of GBV‐C infection among haemodialysis patients who have and do not have HCV infection. GBV‐C RNA was detected in sera of randomly selected 98 anti‐HCV‐positive and 85 ‐negative patients on dialysis by reverse transcription‐polymerase chain reaction using two sets of amplification primers made from the reported sequences of the non‐structural protein 3 and 5’ untranslated regions. In these patients, liver function tests were carried out at regular intervals. There were six patients who were coinfected with HCV and GBV‐C and three who had only GBV‐C RNA. All had a history of past blood transfusion. The onset of mild hepatitis was identified in three HCV‐negative patients; elevation of alanine aminotransferase (ALT) following blood transfusion was very mild but recognizable, and aspartate aminotransferase (AST) was higher than ALT. In two of six coinfected patients, the onset of liver disease was recognized with a peak ALT of 72 and 90 IU/L, respectively. Two of these six were Amplicore (HCV‐RNA) negative and asymptomatic, two had low‐grade HCV viraemia and two moderate‐grade HCV viraemia. Of the 98 anti‐HCV‐positive cases, 41 were thought to have had nosocomial infection of HCV or non‐A, non‐B virus; none of them had GBV‐C. GBV‐C RNA was negative in nine patients who had chronic non‐A‐E hepatitis. GBV‐C infection was detected in 6.1% of anti‐HCV‐positive and in 3.5% of‐negative dialysis patients. All had blood transfusion in the past, and there was no evidence of patient‐to‐patient spread of GBV‐C in hospital. The liver disease was very mild and self‐limited in GBV‐C infection alone. The natural history of coinfected patients may be similar to that of those with chronic HCV infection, but the liver disease appears to be milder.
An unusual choledochal cyst
Authors: GUPTA ROHIT , PRUTHI HARJEET SINGH , BAIJAL SANJAY SARAN , SARASWAT VIVEK ANAND
Published: March 2008

We report a case of Caroli's disease associated with diverticulae and choledochocele of the common bile duct, a wide pancreaticobiliary angle and non‐cirrhotic portal hypertension. This patient presented with recurrent episodes of cholangitis. To our knowledge, such a range of findings in the same patient has not been previously reported in the English language literature.