bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatitis E: An overview and recent advances in clinical and laboratory research
Authors: Aggarwal Rakesh , Krawczynski Krzysztof
Published: March 2003

Hepatitis E virus (HEV) is a non‐enveloped RNA (7.5 kb) virus that is responsible for large epidemics of acute hepatitis and a proportion of sporadic hepatitis cases in southeast and central Asia, the Middle East, parts of Africa and Mexico. Hepatitis E virus infection spreads by the faecal–oral route (usually through contaminated water) and presents after an incubation period of 8–10 weeks with a clinical illness resembling other forms of acute viral hepatitis. Clinical attack rates are the highest among young adults. Asymptomatic and anicteric infections are known to occur. Chronic HEV infection is not observed. Although the mortality rate is usually low (0.07–0.6%), the illness may be particularly severe among pregnant women, with mortality rates reaching as high as 25%. Recent isolation of a swine virus resembling human HEV has opened the possibility of zoonotic HEV infection. Studies of pathogenetic events in humans and experimental animals reveal that viral excretion begins approximately 1 week prior to the onset of illness and persists for nearly 2 weks; viraemia can be detected during the late phase of the incubation period. Immunoglobulin M antibody to HEV (anti‐HEV) appears early during clinical illness but disappears rapidly over a few months. Immunoglobulin G anti‐HEV appears a few days later and persists for at least a few years. There is no specific treatment available for hepatitis E virus infection. Ensuring a clean drinking water supply remains the best preventive strategy. Recombinant vaccines are being developed that may be particularly useful for travellers to disease‐endemic areas and for pregnant women.
Evaluation of autonomic nervous function in patients with essential hypertension complicated with peptic ulcer
Authors: Yukinaka Michiko , Nomura Masahiro , Saijyo Tetsuya , Nada Tomomi , Miyajima Hitoshi , Kondo Yuki , Saito Ken , Nakaya Yutaka , Ito Susumu
Published: March 2003

Background and Aims
: The relationship between peptic ulcer, autonomic activity and the incidence of Helicobacter pylori infection in untreated hypertensive patients complicated with peptic ulcer were evaluated.

Methods
: Ten hypertensive patients with peptic ulcer (HT‐PU group), 15 untreated essential hypertensive patients without peptic ulcer (HT group) and 10 normal subjects (N group) were enrolled, and a power spectral analysis was performed in each subject. A biopsy urease test was used to detect infection by H. pylori.

Results
: No significant differences were observed in the values of mean low‐frequency (LF) power between the three groups. However, the mean high‐frequency (HF) power in the HT‐PU group was significantly greater than those of the HT and N groups (P < 0.01). The mean LF/HF ratios in the HT‐PU and HT groups were significantly greater than that of the N group (P < 0.01). With respect to H. pylori infection, no significant differences between the three groups were observed. Sympathetic activity (LF power) was increased in the HT and HT‐PU groups. Furthermore, parasympathetic activity (HF power) was increased in the HT‐PU group.

Conclusions
: These findings suggest the participation of increased parasympathetic activity in peptic ulcer patients. Therefore, it is suggested that new techniques, such as spectral analysis of heart rate variability, as used in this study, will clarify the relationship between peptic ulcer and autonomic nervous function.
Clarithromycin‐resistance and point mutations in the 23S rRNA gene in Helicobacter pylori isolates from Japan
Authors: Umegaki Noriko , Shimoyama Tadashi , Nishiya Daisuke , Suto Toshiyuki , Fukuda Shinsaku , Munakata Akihiro
Published: March 2003

Background
: Resistance of Helicobacter pylori to clarithromycin is mostly due to the point mutations in the 23S rRNA. In Japan, however, the frequency of these mutations has not been fully investigated. Furthermore, no study has used gastric biopsy specimens to detect these point mutations.

Methods
: The frequency of primary clarithromycin‐resistant H. pylori was examined by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP). Eighty‐two strains (42 isolated from patients with gastric cancer and 40 isolated from patients with chronic gastritis) were examined. Two biopsy specimens obtained from patients in whom eradication therapy including clarithromycin had failed were also studied.

Results
: Either A2143G or A2144G point mutation was detected in 90% of clarithromycin‐resistant H. pylori strains. Eight out of 82 strains (9.8%) had either A2143G or A2144G point mutation. Only one out of 42 strains in patients with gastric cancer had A2143G mutation, whereas five strains had A2144G and two had A2143G mutations in 40 strains isolated from control subjects. The proportion was significantly lower in patients with early gastric cancer (P < 0.05). This PCR‐RFLP was also applicable for DNA samples extracted from biopsy specimens and infection of clarithromycin‐resistant H. pylori was observed.

Conclusion
: The results suggest that the point mutation in the 23S rRNA gene is commonly seen in clarithromycin‐resistant H. pylori and it contributes to the treatment failure in Japan. The PCR‐RFLP system is a sensitive method by which to diagnose H. pylori infection as well as a simple method for detecting clarithromycin resistance without bacterial culture.
Acute hepatic failure: A Western perspective
Authors: Ostapowicz George , Lee William M
Published: March 2003

Acute hepatic failure (AHF) is an uncommon, devastating syndrome, which results in death or the need for liver transplantation in more than 50% of cases. While AHF has numerous causes, most cases are due to viral hepatitis and drug toxicity or idiosyncratic reactions. A significant group with indeterminate causation remains, despite careful investigation. In many of these cases a viral aetiology is suspected, although yet not proven. Major differences exist in the aetiology of AHF between the West and Eastern countries. A wider range of aetiologies exists in the West. Common causes include acetaminophen toxicity and idiosyncratic drug reactions, while viral hepatitis is less frequent. Hepatitis E infection is rarely seen in Western countries in contrast to its high prevalence in the East. The mainstay of AHF management is supportive care in an intensive care unit. Liver transplantation is now the standard of care in many Western liver units for individuals who have a less than 20% probability of survival. Lack of availability of donor livers at short notice remains a significant problem. Methods of liver support used while waiting for a donor liver or for the native liver to regenerate include bioartificial livers, extracorporeal liver‐assist devices, extracorporeal whole organ perfusion (human and transgenic pig) and hepatocyte transplantation. The effectiveness of these methods remains unproven and awaits controlled clinical trials. Both transplantation and liver‐support methods require specialized units and expensive and complicated equipment. Further research is necessary to identify modalities of therapy that would be effective as well as widely accessible.
Perihepatic lymphadenopathy in chronic hepatitis C: A complementary diagnostic element?
Authors: Ierna Dario , D’Amico Rosa Anna , Antoci Salvatore , Campanile Enrico , Neri Sergio
Published: March 2003

Background and Aims
: The authors searched for perihepatic lymph nodes during ultrasonography performed for other symptoms in 1222 Sicilian outpatients in order to assess the incidence and possible significance of the association of perihepatic lymph nodes and chronic hepatitis C.

Method
: One or two lymph nodes were observed in 184/1222 patients, and 142 of these 184 were anti‐hepatitis C virus (HCV) positive.

Results: Our results confirmed a very high incidence of perihepatic lymphadenopathy during chronic hepatitis. The concomitant presence of HCV virus and perihepatic lymph nodes may confirm the marked lymphotropism of this virus.

Conclusion
: As anti‐HCV positivity is frequent in asymptomatic subjects with normal alanine aminotransferase concentrations, the authors believe that searching for sentinel perihepatic lymph nodes during abdominal ultrasonography could be recommended in routine diagnostic screening for HCV infection. Any perihepatic lymph nodes detected by this method could pinpoint subjects for whom more specific examinations are required, especially in areas where the virus is particularly endemic.
Alcohol consumption induces hepatocyte apoptosis in patients with chronic hepatitis C infection
Authors: Pianko Stephen , Patella Shane , Sievert William
Published: March 2003

Background
: Epidemiological studies have established that heavy alcohol consumption in persons with chronic hepatitis C infection is associated with advanced liver disease, including cirrhosis. The cellular mechanisms underlying this process, which appear to occur over decades, are unknown. Increased hepatocyte apoptosis has been observed in association with hepatitis C infection. The aim of this study was to evaluate the relationship between alcohol consumption and hepatocyte apoptosis in hepatitis C‐infected patients.

Methods
: Liver tissue from 20 hepatitis C‐infected patients with variable alcohol consumption, and 10 normal control subjects was examined for hepatocyte apoptosis, proliferation and bcl‐2 expression.

Results
: Hepatocyte apoptosis was significantly greater in hepatitis C‐infected patients than in controls. In hepatitis C‐infected patients, significantly more hepatocyte apoptosis was seen in those consuming at least 30 g per day of alcohol compared with those drinking less than 10 g daily. Bcl‐2, an inhibitor of apoptosis, was not detected in liver tissue from patients with the highest ethanol intake and rate of hepatocyte apoptosis. In contrast, patients drinking lesser amounts of ethanol had lower rates of hepatocyte apoptosis and more frequent bcl‐2 expression.

Conclusions
: This study confirms that both hepatitis C infection and ethanol consumption induce hepatocyte apoptosis in humans. Ethanol‐induced hepatocyte apoptosis has previously been shown only in animal models of alcohol‐related liver injury. The precise role of apoptosis in the pathogenesis of hepatitis C‐related liver injury remains unclear, but its induction may be related to downregulation of bcl‐2 expression associated with ethanol consumption.
Use of immunomodulatory therapy (other than interferon) for the treatment of chronic hepatitis B virus infection
Authors: Lau George Kk
Published: March 2003

Chronic hepatitis B virus (HBV) infection is a major health threat in Asia. In order to design a better therapeutic regimen, the underlyng mechanism of HBV viral persistence must be understood. Immunological studies have found that impaired HBV virus‐specific T cell reactivity is the major cause of chronic infection, whereas strong and multispecific T cell responses to HBV are associated with long‐term control, but not elimination of the virus. Furthermore, in the serological clearance of hepatitis B surface antigen (HBsAg) in allogeneic haematopoietic cell transplantation, HBsAg seroconversion is associated with activation of the donor’s hepatitis B core antigen‐specific CD4+ T lymphocytes. This suggests that the donor’s hepatitis B core antigen‐specific CD4+ T cells provide ‘intermolecular T cell help’ for the HBsAg seroconversion. These findings are relevant to the future development of therapeutic vaccines or DNA vaccine as immunotherapy for chronic hepatitis B. Apart from interferon‐α, thymosin α1 (Tα1) has been investigated for treatment of chronic hepatitis B. Meta‐analysis of 4 randomized controlled studies investigating the safety and efficacy of Tα1 monotherapy for the treatment of chronic hepatitis B showed that 6 months treatment with Tα1 (1.6 mg twice weekly) almost doubles the sustained response rate (36%) compared with controls (19%; P = 0.04). However, more specific immunological approaches are being developed; notably, hepatitis B core antigen‐based therapeutic vaccine was found to induce T cell proliferative responses in chronically infected hepatitis B patients to the T helper epitope included in the construct. However, the cytokine profile observed suggested the induction of a T helper 0/T helper 2 CD4+ T cell response rather than T helper 1 response. Thus, its combination with interferon‐γ or interleukin‐12, which might reverse the CD4+ T cell response, should be considered. In the future, it is likely that different types of combination therapy may have to be tailor‐made for chronic HBV infection with different virological and immunological profiles and different degrees of liver damage.
Functional dyspepsia and Helicobacter pylori infection: A recent consensus up to 1999
Authors: Miwa Hiroto , Sato Nobuhiro
Published: March 2003

With accumulated evidence for a close relationship between Helicobacter pylori infection and many gastric disorders, the idea that this infection may invoke dyspeptic symptoms appears realistic. If curative therapy for H. pylori can bring about relief of symptoms in these patients, we would possess a new therapeutic tool for functional dyspepsia. Although there have been many clinical trials on this issue, the benefits of H. pylori treatment have been controversial. However, several large‐scale clinical studies have been very recently published, and suggest a specific direction on this clinical question. From these results, the current consensus is that H. pylori infection does not directly affect symptoms in patients with functional dyspepsia. However, most clinical trials have been performed on Western populations, and there are few reports from Asian countries. Our recent study on the Japanese population also supported the consensus, that is, a negative relationship between H. pylori infection and symptoms in functional dyspepsia patients.
Association of human leucocyte‐DR and DQ antigens in coeliac disease: A family study
Authors: Agrawal S , Gupta A , Yachha Sk , Müller‐Myhsok B , Mehrotra P , Agarwal Ss
Published: March 2003

Background and Aims
: No family studies regarding the association of coeliac disease with the human leucocyte antigen (HLA)‐DQ locus are available. Moreover, no HLA studies have been carried out in coeliac disease patients from India. The aim of this study was to study the HLA class II (DR and DQ) antigens in children with coeliac disease and in their first‐degree relatives.

Methods
: Fifteen children with coeliac disease and their first‐degree relatives (birth parents of all the coeliac disease patients and fifteen siblings) were studied. A group of 123 healthy unrelated and ethnically matched subjects were used as controls. The HLA‐DR and ‐DQ typing was carried out by a complement‐dependent microlymphocytotoxicity assay. The transmission disequilibrium test was used for analysis of results.

Results
: There was no association of coeliac disease with DR phenotypes. Ninety‐three per cent of patients (14/15) carried the DQ2 allele. DQ2 was transmitted in 15 of 19 informative cases (transmission probability of 79%, χ2 6.368 with 1 df, nominal P = 0.012 and P value corrected for multiple test = 0.035). The haplotype relative risk associated with DQ2 was 5.71 (95% confidence interval 1.71–16.28).

Conclusion
: Coeliac disease in Indian children is predominantly associated with HLA‐DQ2.
Acute liver failure: Established and putative hepatitis viruses and therapeutic implications
Authors: Williams Roger , Riordan Stephen M
Published: March 2003

Abstract Any virus that can cause an acute hepatitis will, on occasion, give rise to acute liver failure. Such infections can be separated into those due to the primary hepatitis viral infections A to E and those where hepatitis occurs as part of a systemic viral infection, as with infection with, for instance, Epstein–Barr virus, cytomegalovirus, Varicella zoster virus, adenovirus and Herpes simplex virus. In general, the frequency with which the different hepatitis viruses are responsible for acute liver failure is related to their underlying prevalence in particular countries. An apparent exception is the striking geographical variation in the reported prevalence of acute liver failure due to hepatitis C virus infection, with a much higher proportion of cases generally attributed to this agent in Japan and Taiwan than in Western countries. Recent work has focused on the possible importance of mutant hepatitis B viral strains, co‐ and super‐infection with known hepatitis viruses and certain newly described agents that may account for otherwise unexplained cases of acute liver failure. Despite an improved understanding of the pathogenesis of complicating cerebral oedema and advances in general supportive care, it is likely that the most severely affected patients with acute liver failure due to viral causes will survive only with liver transplantation, at least until approaches for promoting adequate liver regeneration are successfully developed and implemented.
Divergence of mucosal and motor effects of insulin‐like growth factor (IGF)‐I and LR3IGF‐I on rat isolated ileum following abdominal irradiation
Authors: Fraser R , Frisby C , Schirmer M , Blackshaw La , Langman J , Howarth G , Yeoh Ek
Published: March 2003

Abstract Background and Aims: In addition to its beneficial effects on small intestinal mucosal development and repair, insulin‐like growth factor (IGF)‐I has also been reported to improve neural function in toxic neuropathies. It has recently been recognized that enteric neural abnormalities contribute to the small intestinal dysmotility observed during and after abdominal radiotherapy for gynecological and pelvic malignancy. The aim of the present study was to evaluate the effects of IGF‐I (5 mg/kg per day) and the more potent analog LR3IGF‐I (5 mg/kg per day) on neurally mediated ileal dysmotility following irradiation.

Methods: Intestinal motor activity was recorded from 6–8 cm segments of explanted rat ileum using a miniaturized manometric technique during arterial perfusion with oxygenated fluorocarbon solution. Studies were performed 4 days after treatment with 10 Gy abdominal irradiation. At the time of irradiation, all rats underwent implantation of an osmotic mini‐pump that contained 100 mmol/L acetic acid vehicle (n = 8), IGF‐I (n = 8) or LR3IGF‐I (n = 7). For each experiment, the total number of pressure waves, high‐amplitude long‐duration (defined as > 20 mmHg, > 6 s; HALD) pressure waves and long bursts (> 20) of pressure waves were determined. Ileal segments from 12 non‐irradiated rats were used as controls for manometric studies. In radiotherapy treated animals, the degree of mucosal damage was determined using a standardized histologic scoring system.

Results: The HALD pressure waves were infrequent in non‐irradiated rats but occurred in all irradiated animals. Insulin‐like growth factor‐I and LR3IGF‐I had no effect on the frequency, amplitude or migration characteristics of HALD pressure waves compared with vehicle. Histologic damage was reduced in animals that received IGF‐I and LR3IGF‐I compared with vehicle‐treated animals.

Conclusions: In radiation enteritis, IGF‐I has no effect on neurally mediated small intestinal dysmotility while improving mucosal histology. The disparity between these results suggests that parallel but separate pathologic processes underlie mucosal and motor abnormalities in radiation enteritis.
Sphincter of Oddi dysfunction associated with choledochal cyst
Authors: Craig Alexander G , Chen Long‐Dian , Saccone Gino Tp , Chen John , Padbury Robert Ta , Toouli James
Published: March 2003

Abstract The pathophysiology of choledochal cysts remains unclear, although an association with anomalous pancreato‐biliary junction and the reflux of pancreatic enzymes into the biliary tree is known. Sphincter of Oddi (SO) manometry was performed in three patients with choledochal cysts. All patients exhibited an elevated basal pressure diagnostic of sphincter of Oddi dysfunction. Two patients exhibited anomalous pancreato‐biliary junction. This report suggests an association between the choledochal cyst and sphincter of Oddi dysfunction, and may suggest that SO dysfunction plays a role in choledochal cyst formation.
Iron and hepatocellular carcinoma
Authors: Deugnier Yves , Turlin Bruno
Published: March 2003

Abstract The high prevalence of hepatocellular carcinoma (HCC) in genetic hemochromatosis (GH) and the association between increased body iron stores and occurrence of HCC in subjects with iron overload unrelated to GH, and the experimental evidence of a co‐carcinogenic role of iron strongly support that iron is involved in the development of HCC.
Intestinal dysfunction in liver cirrhosis: Its role in spontaneous bacterial peritonitis
Authors: Ramachandran Anup , Balasubramanian Kunnissery A
Published: March 2003

Spontaneous bacterial peritonitis is a common illness in patients with cirrhosis and ascites that occurs without any apparent focus of infection. Bacterial translocation plays an important role in spontaneous bacterial peritonitis and it is evident from a variety of studies that the gut is a major source of this bacteria. Gut motility alterations, along with bacterial overgrowth and changes in intestinal permeability, probably play a role in this bacterial translocation. The present review looks at the role of the intestine in spontaneous bacterial peritonitis induced by liver cirrhosis and the factors influencing bacterial translocation in this disease.
TT Virus is shown in the liver by in situ hybridization with a PCR‐generated probe from the serum TTV‐DNA
Authors: Ohbayashi Hideo , Tanaka Yujiro , Ohoka Shinya , Chinzei Ryouko , Kakinuma Sei , Goto Mieko , Watanabe Mamoru , Marumo Fumiaki , Sato Chifumi
Published: March 2003

Background and Aim: It has been a conflicting issue whether TT virus (TTV), a newly isolated DNA virus from a patient with liver injury of unknown cause, is a causative agent of acute and/or chronic hepatitis. TT Virus DNA titers were shown to be 10–100‐fold greater in liver tissue than in serum, whereas the majority of TTV‐positive cases had no biochemical or histological evidence of significant liver damage. We therefore attempted in situ hybridization to investigate whether TTV is hepatotropic.

Methods: Because of the marked divergence in TTV genome types, a template for TTV‐DNA (coding region for N22 clone) was amplified and labeled with digoxigenin‐dUTP by using hemi‐nested PCR from the serum, then DNA probes were applied to the liver sections of the same case. After hybridization, the probes were visualized immunohistochemically. Besides TTV‐DNA‐negative cases, competitive inhibition experiments with unlabeled probes were performed to confirm the specificity.

Results There were no positive signals in the negative controls, and the intensity of positive signals was markedly diminished in the competitive inhibition experiments. No cross‐hybridization with different genotype probes also confirms the specificity. Under the optimal conditions, the positive signals were located in the cytoplasm of the hepatocytes in eight of nine TTV‐DNA‐positive cases. The signals were not seen in non‐parenchymal cells of the liver.

Conclusion: TT Virus is proved to be hepatotropic by in situ hybridization.
Systemic and splanchnic hemodynamics following hemorrhage and volume restitution with Haemaccel in portal hypertensive rats: The effect of propranolol
Authors: Hilzenrat Nir , Arish Arie , Yaari Arieh , Sikuler Emanuel
Published: March 2003

Background and Aims: Recently, we found in a portal hypertensive rat model that hemorrhage and volume restitution with Haemaccel, a low viscosity plasma expander, induced an increase in cardiac output and portal venous inflow. The present study was conducted to evaluate whether pretreatment with propranolol will attenuate these hyperdynamic changes.

Methods: Portal hypertension was induced by portal vein constriction. Treatment was initiated 14–21 days later. Propranolol (30 mg/kg per day) or water were administered for 7 days via a gastric gavage. Under ketamine anesthesia, 18 h after the last given dose, blood was withdrawn at a constant rate of 0.3 mL/min for 15 min followed by a 15‐min stabilization. Haemaccel was infused at the same rate and volume used for withdrawal. Hemodynamic measurements were performed after volume restitution in both groups by using radioactive microspheres.

Results: Eight rats were studied in each group. In the propranolol‐treated animals, portal venous inflow was decreased (2.4 ± 0.8 vs 3.8 ± 0.7 mL/min per 100 g bodyweight; P < 0.01), while splanchnic arteriolar and porto‐collateral resistance were increased (52.8 ± 21.0 vs 32.8 ± 13.0 and 6.0 ± 1.4 vs 4.1 ± 0.7 mmHg × min × 100 g bodyweight/mL; P < 0.05, respectively). Cardiac output, mean arterial pressure, heart rate, total peripheral resistance and portal pressure were not significantly different between the two groups.

Conclusion: In this model, pretreatment with propranolol prevented the increase in portal venous inflow, which occurs following hemorrhage and volume restitution with Haemaccel. Although caution should be taken in extrapolating data from animal models to humans, our results suggest that volume replacement during a portal hypertensive‐related bleeding episode may be safer in a patient treated with non‐selective β‐adrenoreceptor antagonists.
Lamivudine treatment for hepatitis B reactivation in HBsAg carriers after organ transplantation: A 4‐year experience
Authors: Liu Chun‐Jen , Lai Ming‐Yang , Lee Po‐Huang , Chou Nai‐Kuan , Chu Shu‐Hsun , Chen Pei‐Jer , Kao Jia‐Horng , Jen Yung‐Ming , Chen Ding‐Shinn
Published: March 2003

Background: Reactivation of hepatitis B after organ transplantation in hepatitis B surface antigen (HBsAg) carriers may be fatal. In this study, we reported our experience of lamivudine treatment in HBsAg carriers who had post‐transplant reactivation of hepatitis B.

Methods: The patients were 15 men and one woman. Nine received kidney transplants, six received heart transplants, and one received a lung transplant. They developed a reactivation of hepatitis B 1–101 months (median, 14 months) after transplantation. They received lamivudine 100 mg daily on a compassionate‐use basis, and had regular follow ups. The median pretreatment total serum bilirubin level was 3.0 mg/dL, and the alanine aminotransferase level was 357 U/L. Four of the 16 patients were positive for HBeAg. The serum hepatitis B virus (HBV) DNA levels were > 3000 pg/mL in 13 (81%) patients. Three were coinfected with hepatitis C virus.

Results: The overall survival rate was 75%. All four fatal cases had a pretreatment total serum bilirubin level of ≥ 3 mg/dL. Serum HBV‐DNA soon became undetectable in 12 survivors. Of the 12 survivors, after a median treatment period of 101 weeks, a lamivudine‐resistant strain with variation in the YMDD motif of the HBV polymerase gene developed in three (25%). None had significant adverse reactions to lamivudine treatment.

Conclusions: These results indicated that lamivudine is effective in the treatment of post‐transplant hepatitis B reactivation, including patients with dual chronic hepatitis B and C. Early recognition of HBV reactivation and prompt lamivudine treatment are important to prevent mortality.
Calcium‐parathyroid hormone‐vitamin D axis and metabolic bone disease in chronic viral liver disease
Authors: Duarte Mônica Pc , Farias Maria Lucia F , Coelho Henrique Sérgio M , Mendonça Laura Mc , Stabnov Lisa Md , Oliveira Maria Do Carmo D , Lamy Ricardo A , Oliveira Dhianah S
Published: March 2003

Background: The main process involved in hepatic osteodystrophy seems to be osteoporosis, but decreased 25‐hydroxylation of vitamin D might lead to osteomalacia and secondary hyperparathyroidism.

Methods and Results: We studied bone mineral density (BMD) by using DEXA‐Expert Lunar, biochemical markers of bone turnover and calcium‐parathyroid hormone (PTH)‐vitamin D axis in 100 patients with chronic viral hepatitis secondary to hepatitis C virus: 49 non‐cirrhotic (NCir) and 51 with cirrhosis (Cir) confirmed by liver biopsy and/or clinical and biochemical features. When compared to the age‐matched population, 25% of the patients had low BMD at the lumbar spine (LS), 26.2% at Ward's triangle, 15.5% at the femoral neck (FN), and 20.2% at the trochanter. No difference was found either between Cir and NCir groups or between sexes. Urinary N‐telopeptide was increased in 31.86% of the patients, and negatively correlated with BMD at the LS and trochanter (P < 0.02). Serum bone‐specific alkaline phosphatase was elevated in 21% of the patients and negatively correlated with BMD at the trochanter and Ward's triangle (P < 0.02). Fasting 25‐hydroxyvitamin D was low in only three Cir patients, with no difference between the Cir and NCir groups, but it was higher in men (51.8 ± 16.0 ng/mL) compared to women (40.4 ± 14.4 ng/mL; P = 0.001). Fasting serum calcium was lower in Cir than NCir patients, P = 0.019. Fasting intact PTH was elevated in 42% of the patients, but the mean serum levels were similar in Cir and NCir groups.

Conclusion: We found no evidence of vitamin D deficiency, but cannot exclude the participation of PTH in the high bone turnover and bone loss in the population with chronic viral hepatitis.
Endoscopically demonstrable esophageal changes after Helicobacter pylori eradication in patients with gastric disease
Authors: Yachida Shinichi , Saito Daizo , Kozu Takahiro , Gotoda Takuji , Inui Tetsuya , Fujishiro Mitsuhiro , Oda Ichiro , Okabayashi Takehiro , Kakugawa Yasuo , Ono Hiroyuki , Kondo Hitoshi
Published: March 2003

Background and Aims: An increased prevalence of reflux esophagitis has been reported following Helicobacter pylori (H. pylori) eradication in patients with duodenal ulcers in Western countries. However, it has remained unknown whether this might also appertain to individuals with other diseases. We therefore carried out this study to determine the effect of eradicating H. pylori infection in a series of Japanese patients.

Methods: Of a total of 203 H. pylori‐positive patients successfully cured of infection, 82 cases (58 males, 24 females) with gastric disease, but not duodenal ulcers, were included in the present study; median age 56 years (range 18–80) and median follow up of 24 months (range 6–65). The patients were investigated clinically and endoscopically at regular intervals.

Results: Mild reflux esophagitis developed after eradication in three of 55 (5.5%) patients formerly without this condition, while it improved after eradication in five of 27 (18.5%) patients, with the disease endoscopically diagnosed prior to eradication. The estimated incidence of esophagitis within 3 years was 4.8% after cure of infection. Short segment Barrett's esophagus developed after eradication in six of 58 (10.3%) patients who did not have it prior to the therapy, while the condition did not improve in 24 patients affected before eradication.

Conclusions: Endoscopic esophageal changes after H. pylori eradication in the present series of Japanese patients were relatively infrequent and mild. This therapeutic approach thus appears to be safe and unproblematic.
Extending the reading time increases the accuracy of rapid whole blood test for diagnosis of Helicobacter pylori infection
Authors: Chen Tseng‐Shing , Chang Full‐Young , Lee Shou‐Dong
Published: March 2003

Background: To evaluate the accuracy of two rapid whole blood tests (the BM‐Test Helicobacter pylori and the QuikPac IV One Step H. pylori Whole Blood Test), and compare this to a conventional quantitative ELISA test (HEL‐p TEST II).

Methods: Helicobacter pylori status in dyspeptic patients was assessed by culture, histology, and rapid urease tests on biopsies from the antrum and corpus. The optimal cut‐off value of the reading time for the rapid blood tests was determined by using the receiver characteristics operative (ROC) curves.

Results: In the 141 patients examined, 89 were infected, 51 were not infected, and one was indeterminate (only positive in either urease test or histology). Areas under ROC curves were greater in the BM‐Test compared with the QuikPac IV (0.948 vs 0.840, P < 0.01), with their most appropriate cut‐off reading times at 360 and 395 min, respectively, rather than 10 min as suggested by the manufacturer. The sensitivity and specificity were 94.4% and 94.1% at 360 min, and 74.2 and 96.1% at 10 min for the BM‐Test; 80.9, 76.5 at 395 min and 3.4 and 100% at 10 min for the QuikPac IV. The antibody titer of the quantitative ELISA test was negatively correlated with the reaction time of the two rapid blood tests in H. pylori‐infected patients (P < 0.05, r = –0.3).

Conclusions: The BM‐Test is an appropriate office‐based test for diagnosing H. pylori infection in Chinese patients. Extending the reading time would facilitate the readability of rapid blood tests with a resultant increase in accuracy.
Correlation of rectum‐associated lymph nodules with the development of experimentally induced acute colonic inflammation in rats
Authors: Ichikawa Sanae , Gu Shouzhi , Yamashita Akira
Published: March 2003

Background and Aims: The mechanisms of inflammation in ulcerative colitis occurring initially in the rectum and then extending throughout the colon are still unknown. The aim of this study is to investigate the correlation of rectum‐associated lymph nodules (RALN) and the development of a dextran sulfate sodium‐induced experimentally acute colonic inflammation in rats.

Methods: We immunohistochemically analyzed the lymph nodules in the rectal region of rats using monoclonal antibodies to specific markers.

Results: Rectum‐associated lymph nodules resembled the Peyer's patches, where CD4+, CD8+ lymphocytes and Mar 1+ macrophages were observed. After the administration of dextran‐sulfate sodium (DSS), RALN showed hypertrophy with an increase in the number of CD4+, CD8+, and interleukin (IL)‐2R+ lymphocytes in the periphery, as well as Mar 1+ macrophages in the entire region. Concurrently, platelet/endothelin cell adhesion molecule‐1 (PECAM–1+) blood vessels, including high‐endothelial venules (HEV), were increased in number in the interfollicular areas. Furthermore, a number of small lymph nodules varying in size were observed in the upper region of the rectum. Some of them were initially confined to the lamina propria mucosae, and became large enough to extend deeper into the tela submucosa. These DSS‐induced lymph nodules contained large numbers of CD4+ lymphocytes, IL‐2R+ lymphocytes, and Mar 1+ macrophages.

Conclusions: The pathological changes of ulcerative colitis were well correlated with the development of both RALN and DSS‐induced lymph nodules. The immunological reaction that occurred in DSS‐induced lymph nodules is significantly associated with the expansion of colitis from the lower region of rectum to the upper region of rectum and colon.
Therapeutic vaccination in chronic hepatitis B
Authors: SENTURK HAKAN , TABAK FEHMI , AKDOGAN MERAL , ERDEM LEVENT , MERT ALI , OZARAS RESAT , SANDER ERSAN , OZBAY GULSEN , BADUR SELIM
Published: March 2003

Aims: The aim was to test the efficacy of a pre‐S2‐containing vaccine (Genhevac‐B) in chronic hepatitis B (CHB). Twenty‐five naive patients (22 male, three female; median age 35; range: 6–69 years) with CHB were recruited. The inclusion criteria were: hepatitis B e antigen (HBeAg) positive or HBV‐DNA detectable with liquid hybridization; alanine aminotransferase (ALT) is at least 1.5‐fold the upper normal limit and histological evidence of chronic hepatitis.

Methods: In the first period, all patients received monthly injections of 20, 40 and 60 μg of the vaccine. One month after the last injection, patients who still had HBV‐DNA were divided into two randomly assigned groups. While the patients in the first group and the patients who lost HBV‐DNA in the first period continued to receive monthly injections of 20 μg vaccine for a further 6 months, the patients in the second group received 9 MU interferon α‐2b (Roferon‐A), three times per week using the same method as for the first group. Patients were followed up after 12 months without treatment. Response was defined as the loss of HBV‐DNA and normalization of ALT.

Results: Six of the 25 patients lost HBV‐DNA after 3 months. Nine of the remainder were randomly placed in the first group (vaccine‐only) and 10 were placed in the second group (vaccine + interferon). End‐of‐treatment response was achieved, overall, 8/15 from the vaccine group and 6/10 from the combination. One patient from each group relapsed during the follow up. Overall, the sustained response (SR) rate was 46% (7/15) in the vaccine group, and 50% (5/10) in the combination group. Histological improvement was achieved in 6/7 SR with vaccine‐only and all five with combination treatment, while 1/8 of failures of vaccine and 2/5 of failures of combination improved.

Conclusions: It was concluded that Genhevac‐B decreases serum HBV‐DNA levels in the majority of patients with CHB and sustained clearance was achieved in some patients. Combination of interferon‐α with Genhevac‐B is effective for the vaccine failures and may increase sustained response compared to interferon‐α alone. However, the mechanism of action is yet to be explained.
Mediation of transcatheter arterial chemoembolization induced gastric slow‐wave dysrhythmia by endogenous prostaglandin1
Authors: CHANG CHI‐SEN , YANG SHENG‐SHUN , YEH HONG‐ZEN , KO CHUNG‐WANG , LIEN HAN‐CHUNG , CHEN GRAN‐HUM
Published: March 2003

Background and Aims: In recent years, gastric slow‐wave dysrhythmias induced by transcatheter arterial chemoembolization (TACE) have been observed. Enhanced endogenous prostaglandin may be a possible mechanism for the myoelectrical changes. The aim of this study was to evaluate whether the gastric slow‐wave dysrhythmias induced by TACE may be mediated by ketoprofen, a prostaglandin synthesis inhibitor.

Methods: Twenty‐three patients with hepatocellular carcinoma (HCC) admitted for TACE were enrolled. A follow‐up TACE was scheduled to take place 2 months later. During the next admission for TACE, 50 mg of ketoprofen was given intramuscularly 12 h for 3 days, beginning 48 h before TACE, as premedication. Cutaneous electrogastrography (EGG) was performed before and within 24 h after TACE.

Results: The results showed that the change in the fasting EGG parameters after TACE without premedication was not statistically significant. However, the postprandial EGG parameters, including the dominant frequency (DF); the percentages of DF in the normal, bradygastric and tachygastric range; along with the dominant frequency instability coefficient, deteriorated significantly after the procedure (P < 0.01). After the follow‐up TACE with ketoprofen premedication, neither the fasting nor postprandial EGG parameters in the control group changed significantly.

Conclusions: Gastric slow‐wave dysrhythmias induced by TACE may be mediated by ketoprofen, a prostaglandin synthesis inhibitor, in HCC patients. However, the improvement in the gastric myoelectrical activity does not eliminate the degree of nausea/vomiting after TACE.
Acute and 7‐day portal pressure response to carvedilol and propranolol in cirrhotics
Authors: DE BINAY K , DAS DEBASISH , SEN SAMBIT , BISWAS PRANAB K , MANDAL SANJAY K , MAJUMDAR DEBASIS , MAITY AJIT K
Published: March 2003

Background Carvedilol, a non‐selective beta‐ and α‐1 blocking agent, has portal hypotensive action. This study evaluates the acute and 7‐day response to carvedilol, and compares it to that of propranolol.

Methods Thirty‐six cirrhotics were randomized into two groups of 18 each, and treated with carvedilol or propranolol. Hepatic venous pressure gradient (HVPG) was measured before and 90 min after either 25 mg carvedilol or 80 mg propranolol was administered orally, and again 7 days after 12.5 mg carvedilol daily or 80 mg propranolol daily, respectively. ‘Responders’ were defined as those with HVPG reduction of ≥ 20%.

Results With carvedilol, 11/18(61.1%) and 11/17(64.7%) patients responded acutely and after 7 days, respectively, while 9/18(50%) and 10/16(62.5%) did so to propranolol. However, HVPG reduction (percent) by carvedilol was not superior to that by propranolol either acutely (27.67 ± 31.49 compared to 22.98 ± 27.40, P = 0.6) or after 7 days (28.2 ± 29.05 compared to 23.25 ± 20.15, P = 0.6). With carvedilol, the acute HVPG response (P < 0.001) and responder status (P = 0.018) were good predictors of the response after 7 days, but were weak predictors in the case of propranolol (0.1 > P > 0.05 and P = 0.059, respectively). On carvedilol, only one patient (with ascites) developed symptomatic systemic hypotension with oliguria.

Conclusion Carvedilol is a relatively safe, effective portal hypotensive agent, both acutely and over 7 days, but not superior to propranolol, at least in Indians. The acute hemodynamic response seems promising in predicting long‐term response.
Pediatric liver disease in the United States: Epidemiology and impact
Authors: ARYA GAJRA , BALISTRERI WILLIAM F
Published: March 2003

Liver diseases which affect children are unique. Diseases such as inborn errors of metabolism are fertile grounds for investigation. Study of these ‘experiments of nature’ will provide insight into hepatobiliary function and lead to novel treatment modalities. Successful treatment or prevention of liver disease in children will have long‐term implications. This report describes the current burden of pediatric liver disease and offers approaches to intervention. © 2002 Blackwell Publishing Asia Pty Ltd
Study of the motile activity of the colon in rectal inertia constipation
Authors: SHAFIK AHMED , AHMED ISMAIL
Published: March 2003

Background: We have recently demonstrated that rectal distension effected left colonic contraction, which probably acts to feed the rectum with fecal matter each time the rectum distends and evacuates its contents. This effect was postulated to occur through the recto‐colic reflex. As the colonic status in rectal inertia constipation was scarcely addressed in the literature, we investigated this point.

Methods: The response of the colonic pressure to rectal balloon distension in increments of 10 mL of water was studied in 38 patients with rectal inertia constipation (IC) (age 42.6 ± 14.3 years, 29 women) and 12 healthy volunteers (40.9 ± 12.2 years, nine women). The rectal and colonic pressures were measured by saline‐perfused tubes connected to a pneumohydraulic infusion system. The rectum was distended by a condom applied to the end of a 10‐F catheter.

Results: The rectal and left colonic resting pressures were significantly
lower in the patients than in the controls (P < 0.5, P < 0.05,
respectively). In the healthy volunteers, rectal distension up to first rectal sensation
produced no significant rectal or colonic pressure changes (P > 0.05, P
> 0.05). At urge, rectal and left colonic pressures increased significantly (P
< 0.001, P < 0.001, respectively), but there were no changes in the
right colonic pressure (P > 0.05). The colonic response lasted as long
as the rectum was distended. In IC, patients did not perceive the first rectal or
urge sensation up to a rectal balloon filling of 300 mL; there was no rectal or colonic
pressure response (P > 0.05, P > 0.05).

Conclusion: In normal subjects, left colonic contraction on rectal distension probably acts to feed the rectum with fecal material. In IC, the low left colonic resting pressure assumedly points to left colonic hypotonia which appears to aggravate the constipation produced by the inertic rectum. Furthermore, non‐response of the left colon to rectal distension probably impedes rectal feeding with fecal matter and enhances constipation.

© 2002 Blackwell Science Asia Pty Ltd
Long‐term quality of life of postoperative rectal cancer patients
Authors: HAMASHIMA CHISATO
Published: March 2003

Abstract

Background:
The long‐term quality of life (QOL) of postoperative rectal cancer patients has not been previously investigated in Japan and may vary depending on the surgical technique used (i.e. with or without a stoma).

Methods:
The Kanagawa Cancer Registry was used to select 348 rectal cancer patients who underwent surgery at the St Marianna University Hospital between 1978 and 1997. Of these, 164 surviving patients were sent a postal survey consisting of the Japanese EuroQol instrument with an additional questionnaire on present symptoms and lifestyle.

Results and conclusions:
One hundred and ten responses were received, including 38 from stoma patients. The presence of a stoma did not affect the QOL of the male patients, while it did affect that of the female patients. The QOL of the long‐term survival group was associated with several items concerning lifestyle, symptoms and usual activity, and the association did not depend on the presence of a stoma. The long‐term QOL could be recognized according to the characteristics of rectal cancer patients, independent of the presence of a stoma.

© 2002 Blackwell Publishing Asia Pty Ltd
Management of bleeding in the cirrhotic patient
Authors: Chung Sydney
Published: March 2003

Abstract  Important advances have been made in the management of variceal bleeding. Despite these advances, bleeding in the patient with cirrhosis remains one of the most demanding clinical challenges that a gastroenterologist or gastrointestinal surgeon may face. The aim is to identify the source of bleeding, control active bleeding and prevent rebleeding. This requires a multidisciplinary team, and the optimal management algorithm depends on the clinical circumstance of the patient and the local availability of endoscopic, radiological and surgical expertise. Injection sclerotherapy is effective in stopping acute variceal bleeding, but has the drawback of a high incidence of complications. Endoscopic variceal ligation is just as effective, and is associated with fewer complications. An overtube allows repeated introductions of the endoscope to be more tolerable for the patient and protects the airway against aspiration of blood; its use should be encouraged in patients with massive bleeding. Newer ligators can deliver multiple bands without removal of the scope but the high cost of these disposable devices limits their widespread use. Bleeding from gastric varices is even more challenging; the treatment of choice is injection with cyanoacrylate glue. To prevent rebleeding, beta‐blockers are recommended for all patients with large varices (including those which have never bled). Injection sclerotherapy or band ligation, conducted at weekly intervals after the initial control of bleeding, is equally effective at obliterating varices and decreasing the risk of further hemorrhage; band ligation results in fewer complications. Other newer treatment modalities for variceal bleeding, such as somatostatin analogs, transjugular intrahepatic portasystemic shunt and liver transplantation, offer more optimal approaches to control bleeding and prevent rebleeding, but may be prohibitively expensive. Even for the most affluent communities, affordability, cost‐effectiveness, and resource rationing are important considerations in management of patients with cirrhosis complicated by gastrointestinal bleeding.

© 2002 Blackwell Publishing Asia Pty Ltd