bluuebunny/crossref_metadata_2025 huggingface dataset:
Collision tectonics in the New Hebrides arc (Vanuatu)
Authors: Meffre Sebastien , Crawford Anthony J
Published: March 2003

Abstract The New Hebrides island arc in Vanuatu has been significantly modified by collision with several major submarine ridges and plateaux. Bathymetric sections taken at intervals along the arc, perpendicular to the trench, show that prior to collision at 3 Ma the morphology was typical of modern intraoceanic island arcs. Collision has caused uplift of the trench and forearc (up to 6000 m), subsidence around the arc volcanic edifices (up to 2500 m), forming a large intra‐arc basin and uplift of the arc‐backarc transition (up to 2000 m). In the transition zone between collisional and non‐collisional sections of the arc, subsidence occurs in the forearc and uplift occurs around the arc volcanoes. Many of these characteristics are typical of collisions in other Western Pacific island arcs such as the Tonga–Kermadec and Izu–Bonin arcs. The pattern of uplift and subsidence has important implications for the tectonic history of the New Hebrides system. The morphology of the arc shows that collision of the West Torres Massif probably accounts for at least half the uplift. Arrival at 0.7 Ma of the West Torres Massif in the trench may have caused the slowing of subduction in the entire northern half of the arc and not just in the central segment as previously suggested. Re‐equilibration of the arc following collision probably masks any evidence of collision prior to 3 Ma. For example, the Efate re‐entrant, a large indentation in the arc immediately to the south of the collision zone, probably originated as a result of erosion during collision followed by subsidence after collision. The Vanuatu collision shows that the subduction of seamounts and ridges in an intraoceanic arc temporarily changes the arc morphology, allowing the development of angular unconformities and changing the pattern of sedimentation. This provides information which can be used to facilitate recognition of these events in ancient arc‐related sequences.
A critical assessment of new therapies in inflammatory bowel disease
Authors: RUTGEERTS PAUL
Published: March 2003

The only therapy in inflammatory bowel disease (IBD), which up to the mid‐1990s was disease modifying, was immunosuppression with azathioprine. Other ‘standard’ therapies in IBD were merely symptomatic. With the advent of biological therapies, especially the chimeric monoclonal anti‐TNF antibody infliximab, we start to target specific pathogenic disease mechanisms, which allow thorough suppression of the disease process and healing of the bowel in the long term. Moreover, infliximab is the only drug up to the present that allows short‐term healing of fistulizing Crohn’s disease. This therapy is, however, associated with problems of immunogenicity. The formation of antibodies to infliximab jeopardizes the efficacy and is associated with infusion reactions. Optimization of anti‐TNF strategies will occur in the coming years. Another promising therapy is antagonization of α4 integrins and hence, of migration of inflammatory cells to the intestine. It can be expected that more simple therapies using small molecules that inhibit the key cytokines or pro‐inflammatory processes will take over in the next decade. In the current and future approach to IBD therapy immunosuppression with azathioprine or 6‐MP and methotrexate play a central role. At the present time, the combination of infliximab with azathioprine or methotrexate can be regarded as the new standard for the therapy of refractory Crohn’s disease. In ulcerative colitis (UC) much less progress has been made and the value of biological therapy as well as of long‐term management with immunosuppression remains controversial. Probiotics are an attractive treatment option for IBD but studies so far are small and data are not yet convincing.
Hepatitis viruses: A Pandora's box?
Authors: HOWARD COLIN R
Published: March 2003

Abstract  The term hepatitis virus is reserved for those viruses that are predominantly hepatotropic, although several new agents have been assigned to this category in the absence of hepatotropism and clinical disease. The hepatitis viruses can be broadly divided into those transmitted via the fecal‐oral route, and those by blood, blood products and body fluids. Hepatitis A (picornaviridae), hepatitis B (hepadnaviridae) and hepatitis C (flaviviridae) represent the major public health problems. The epidemiology of hepatitis A virus (HAV) and hepatitis B virus (HBV) is changing in response to vaccination. In the case of HAV, older age groups are now deemed at risk, particularly of fulminant hepatitis if exposed over the age of 50. Chronic hepatitis B in some regions is now predominantly of the so‐called precore mutant type where high levels of HBV replication persist in the presence of anti‐hepatitis B virus (HBe) antibodies. The HBV vaccination is among the most cost‐effective health care measures. The epidemiological significance of mutations found increasingly in the HBV S gene isolated from vaccinated children is unclear. Evidence that hepatitis G and TT virus are significant causes of hepatitis is lacking. Of interest, however, is the finding that the related GBV‐B agent of monkeys may be a model for developing new antiviral agents against HCV. Animal models of hepatitis infections are providing new insights into the pathogenesis of hepatitis in humans. Indeed it is possible that hepatitis E is primarily an agent of pigs and other domesticated livestock. Intriguingly, the new TT virus shares many properties with the circoviruses, significant pathogens of chickens and pigs. The challenge in the next decade will be to assess the significance of these new agents in terms of public health and resources. Value judgements will have to be made in assessing the risks associated with blood containing trace amounts of these adventitious agents.

© 2002 Blackwell Publishing Asia Pty Ltd
Long‐term effect of α‐glucosidase inhibitor on late dumping syndrome
Authors: HASEGAWA TAKENAO , YONEDA MASASHI , NAKAMURA KIMIHIDE , OHNISHI KUNIYO , HARADA HIROYUKI , KYOUDA TAKESHI , YOSHIDA YOSHIKAZU , MAKINO ISAO
Published: March 2003

Dumping syndrome commonly occurs after gastrectomy. The late dumping, which is one of the dumping syndromes, is due to postprandial hypoglycaemia caused by an excessive insulin secretion after a sharp rise in plasma glucose. Several treatments, including operation, dietary fibre and somatostatin, have been attempted to relieve dumping symptoms. These treatments take effect through modulation of plasma insulin and glucose levels, but their efficacy is still under consideration. α‐Glucosidase inhibitor attenuates the postprandial increase of plasma glucose levels and is widely used for treatment of non‐insulin‐dependent diabetes mellitus (NIDDM). The acute effect of α‐glucosidase inhibitor on late dumping syndrome has been reported by some studies with test meals. The purpose of this study was to evaluate a long‐term effect of α‐glucosidase inhibitor treatment with ordinary meals in late dumping patients with NIDDM because administration of α‐glucosidase inhibitor is only ethically allowed for diabetic patients in Japan. Six late dumping patients with NIDDM were orally administered α‐glucosidase inhibitor, acarbose (50 or 100 mg), three times a day before each meal for 1 month. Diurnal changes of plasma glucose, insulin and pancreatic glucagon levels were compared before and after the α‐glucosidase inhibitor treatment. All patients had late dumping‐related symptoms, such as weakness, palpitation and dizziness before the induction of α‐glucosidase inhibitor treatment. Patients suffered from a rapid fall in plasma glucose levels from hyperglycaemia at the same time as dumping symptoms. These late dumping‐related symptoms disappeared and a rapid change of plasma glucose and insulin levels were attenuated after the α‐glucosidase inhibitor treatment. These data suggest a long‐term therapeutic efficacy of α‐glucosidase inhibitor for late dumping patients.
Protective role of adrenal glucocorticoids for gastric mucosa in spontaneously hypertensive rats
Authors: Suzuki Hidekazu , Miura Soichiro , Mori Mikiji , Akiba Yasutada , Nagahashi Shoichi , Zweifach Benjamin , Ishii Hiromasa , Schmid‐Schönbein Geert
Published: March 2003

Background: Spontaneously hypertensive rats (SHR) are a representative animal model for disturbance of the pituitary–adrenal axis, as well as disturbance of the autonomic nervous system.

Methods and Results: In this study, we showed that adrenalectomy in SHR‐induced spontaneous gastric ulcer formation. We further investigated how abnormal adrenal secretion is related to the attenuation of gastric ulcerogenesis, in terms of leucocyte infiltration and nitric oxide (NO) formation. Bilateral adrenalectomy, as well as a sham‐operation, were carried out at 12 weeks in hypertensive SHR and Wistar–Kyoto rats (WKY) and observations were made three weeks later. The number of myeloperoxidase (MPO) positive cells, NADPH diaphorase histochemistry and NO synthase (NOS) activity were determined in gastric specimens. Only in adrenalectomized, but not sham‐operated SHR, WKY and adrenalectomized WKY, could gastric ulcers be observed. Although the number of cells positive for MPO was significantly lower in hypertensive SHR than those in WKY, such cells were increased after adrenalectomy in SHR. In contrast, adrenalectomized WKY developed no increase in MPO‐positive numbers. The number of NADPH diaphorase‐positive cells increased after adrenalectomy in both strains, the extent of which was much greater in SHR than in WKY. Although NOS activity in SHR was lower than that in WKY, it was significantly increased after adrenalectomy.

Conclusions: Our data show that the development of a significant gastric ulceration may be associated with entrapment of activated leucocytes in the gastric mucosa, as well as with an excessive production of NO in adrenalectomized SHR. An enhanced adrenal glucocorticoid may be a key factor for protecting the gastric mucosa in SHR.
A prospective study of the clinical features, manometric findings, incidence and prevalence of achalasia in Singapore
Authors: Ho Khek‐Yu , Tay Hua‐Hui , Kang Jin‐Yong
Published: March 2003

Background
: This study aimed to describe the clinical features, manometric findings, prevalence and incidence of achalasia in Singapore.

Methods
: A total of 615 new patients referred for oesophageal manometry between 1989 and 1996 were examined prospectively. Twenty‐four men and 25 women fulfilled the manometric and clinical criteria for achalasia.

Results
: Their median age of onset of symptoms was 37 years (range 15–71) and 37% first developed symptoms after the age of 50 years. The presenting symptoms were dysphagia (100%), regurgitation (80%), weight loss (67%) and chest discomfort (33%). Five patients (10%) had a history of benign (mostly autoimmune) thyroid disorders. Endoscopy was reported as normal in 10/43 patients (23%) and achalasia was suggested in only 31 (72%) of 43 barium examinations. Lower oesophageal sphincter (LOS) dysfunction was present in 82% of cases. Using data from medical records and from a survey of gastroenterologists and surgeons in Singapore, the prevalence (in 1996) and incidence of achalasia in Singapore were estimated to be 1.8 per 100 000, and 0.3 per 100 000 per year, respectively. The incidence was significantly lower in Malays than Chinese or Indians. The age‐specific incidence of achalasia for both genders followed a bimodal distribution with the larger peak in the sixth decade. No cases of oesophageal carcinoma were identified among these patients.

Conclusion
: Achalasia is an uncommon condition in Singapore. The clinical and manometric features were similar to those described in Western countries.
Hepatitis C in injecting drug‐using women during and after pregnancy
Authors: Latt Noeline C , Spencer Jenean D , Beeby Philip J , M Geoffrey W , Saunders John B , Collins Edith , Cossart Yvonne E
Published: March 2003

Background: A high proportion of female injecting drug users (IDU) have evidence of hepatitis C virus (HCV) infection. We undertook a prospective study of patients attending a clinic for pregnant IDU to determine the impact of pregnancy on the course of HCV infection and whether pregnancy is affected by HCV infection.

Methods: One hundred and thirty‐one IDU were recruited and followed up with liver function tests, HCV serology and HCV‐RNA tests.

Results: Of 131 patients, 125 had HCV antibodies (anti‐HCV positive) at delivery, and of these 62% were HCV‐RNA positive. The anti‐HCV‐negative women were younger and had a shorter duration of drug use than the anti‐HCV‐positive women. There were no differences between viraemic and non‐viraemic women with respect to age, ethnicity, duration of injecting drug use, methadone maintenance dose, hepatitis B exposure or reported high‐risk behaviour. Alanine aminotransferase (ALT) levels were higher and the proportion with ALT > 55 IU/L higher in viraemic women. Viraemia persisted in all 55 women who were viraemic at term. Eleven had an ALT flare post‐partum that was unrelated to viral load and was clinically unsuspected. Four had concurrent elevated γ‐glutamyltranspeptidase and were considered to be drinking alcohol at hazardous levels. Four of 23 women who were HCV‐RNA negative at term became positive during follow up.

Conclusions: Pregnancy does not adversely affect the course of hepatitis C. A modest rebound in ALT levels, but not HCV‐RNA, occurs after delivery in some viraemic women. This supports the theory that immune mechanisms rather than direct viral cytopathology are involved in hepatocyte injury during HCV infection. Hepatitis C infection did not influence pregnancy complications and outcomes.
Where does treatment fit into the strategy to control hepatitis C?
Authors: Desmond Paul
Published: March 2003

The prevalence of hepatitis C varies greatly between countries of the Asia–Pacific region. The incidence of new cases is also markedly different between countries, particularly related to the prevalence of injecting drug use. Overall, the currently available treatments for hepatitis C are unlikely to have a major impact in the control of the infection from a population perspective while success rates are relatively low (20–45% sustained antiviral response) and treatment costs are high. There are some specific situations, such as reducing the incidence of mother‐to‐baby transmission or sexual transmission, where antiviral treatment can be used as a strategy to prevent further infection. The major aims of prevention of hepatitis C infection should lie with public health measures to prevent new infections, particularly amongst injecting drug users, and ultimately the development of an effective vaccine.
Epidemiology of hepatitis B virus infection in the Asia–Pacific region
Authors: Chen Chien‐Jen , Wang Li‐Yu , Yu Ming‐Whei
Published: March 2003

There is a wide variation of hepatitis B virus (HBV) infection in the Asia–Pacific region. The prevalence of chronic HBV infection is lowest (< 1%) in North America, Australia and New Zealand, 2–4% in Japan, 5–18% in China and highest (15–20%) in Taiwan as well as several other countries in South East Asia. Perinatal transmission is common in HBV‐hyperendemic areas. Geographical clusters of horizontal HBV infection have been reported in both high‐ and low‐risk countries. Common sources of infection, including iatrogenic and sexual transmission, have been implicated. Migrant studies indicate the importance of childhood environments in the determination of HBV infection. Rural–urban and ethnic differences in the prevalence of HBV infection have also been reported. There has been a decrease in the prevalence of HBV infection after mass HBV vaccination programmes in some Asia– Pacific countries, which may be due to the intervention of possible transmission routes through the use of disposable syringes and needles, screening of HBV infection markers in blood banks, and prevention of high‐risk tattooing, acupuncture, ear‐piercing and sexual contact. A striking decrease in the incidence of HBV infection and hepatocellular carcinoma has been observed among children in Taiwan and other areas where mass vaccination programmes have been implemented.
Effect of age and Helicobacter pylori infection on gastric acid secretion
Authors: Haruma Ken , Kamada Tomoari , Kawaguchi Hiroyuki , Okamoto Shiro , Yoshihara Masaharu , Sumii Koji , Inoue Masaki , Kishimoto Shinya , Kajiyama Goro , Miyoshi Akima
Published: March 2003

Background
: Whether gastric acid secretion decreases with age is still controversial. With the discovery of Helicobacter pylori, the association of this bacterium with gastric acid secretion has also been discussed. The aim of this study was to investigate the relationship between gastric acid secretion, age and H. pylori infection.

Methods
: The presence of H. pylori infection, the grade of fundic atrophic gastritis (FAG), and gastric acid secretion were investigated in 280 subjects without localized lesions in the upper gastrointestinal tract. Helicobacter pylori infection was confirmed by Giemsa and immunohistochemical staining, and FAG of biopsy specimens was graded on a scale of 0–4.

Results
: Both basal and maximal acid output decreased with age in H. pylori‐positive subjects, while they did not change with age in H. pylori‐negative subjects. Gastric acid secretion decreased with the progression of FAG. An age‐correlated decrease in gastric acid secretion in H. pylori‐positive subjects depended on an increasing prevalence of FAG with age.

Conclusions
: In the population studied, advancing age had no influence on gastric acid secretion in H. pylori‐negative subjects. Gastric acid secretion decreases with age in H. pylori‐positive subjects because of the increasing prevalence of FAG with age.

© 2000 Blackwell Science Asia Pty Ltd
Association of Helicobacter pylori infection with atrophic gastritis and intestinal metaplasia
Authors: Ohkuma Kenji , Okada Mitsuo , Murayama Hiroshi , Seo Mitsuru , Maeda Kazuhiro , Kanda Motonobu , Okabe Nobuo
Published: March 2003

Abstract Aims: To evaluate the effect of Helicobacter pylori infection and aging on atrophy and intestinal metaplasia of the gastric mucosa.

Methods: One hundred and sixty‐three patients were divided into three age groups and underwent an upper gastrointestinal endoscopy where no esophagitis, peptic ulcers, or malignancies were detected. Two biopsy specimens were obtained from the anterior and posterior walls of the antrum and of the fundus. These were used to evaluate the grade of gastritis, bacterial culture and histologic evidence of H. pylori infection.

Results: Helicobacter pylori infection was found to be directly associated with an increased risk of gastritis grade (odds ratio (OR) = 90 (95% CI; 30–270)). An age of 60 years and older along with H. pylori infection was also strongly associated with an increased risk of atrophy (OR = 6.6, (95% CI; 2.9–15.2)); OR = 9.8, (95% CI; 2.7–35.4)), as was intestinal metaplasia of the gastric mucosa (OR = 5.5, (95% CI; 1.7–17.6)); OR = 7.9, (95% CI; 2.8–46.1)). The prevalence of atrophic gastritis increased with advancing age in H. pylori‐infected patients, but no such phenomenon was observed in H. pylori‐uninfected patients. The prevalence of intestinal metaplasia significantly increased with advancing age, irrespective of the presence of H. pylori infection. In addition, H. pylori uninfected female patients had a decreased risk of intestinal metaplasia.

Conclusions: These results suggest that atrophic gastritis is not a normal aging process, but instead is likely to be the result of H. pylori infection, while intestinal metaplasia is caused by both the aging process and H. pylori infection. A decreased risk of intestinal metaplasia found in uninfected female subjects may partly explain the lower prevalence of gastric cancer in females than in males.
Decreased anti‐Saccharomyces cerevisiae antibody titer by mesalazine in patients with Crohn’s disease
Authors: Oshitani Nobuhibe , Hato Fumihiko , Matsumoto Takayuki , Jinno Yoshio , Sawa Yoshinori , Hara Junichi , Nakamura Shiro , Seki Shuichi , Arakawa Tetsuo , Kitano Atsuo , Kitagawa Seiichi , Kuroki Tetsuo
Published: March 2003

Background

Saccharomyces cerevisiae may contribute to the pathophysiology of Crohn’s disease. We determined serum anti‐Saccharomyces cerevisiae antibody (ASCA) levels in patients with inflammatory bowel disease.

Methods and Results

Immunoglobulin G (IgG) ASCA was measured by using an ELISA in serum samples from 19 patients with ulcerative colitis, 18 patients with Crohn’s disease and 7 healthy controls. The ASCA level was significantly higher in patients with ulcerative colitis and patients with Crohn’s disease than in controls, and was significantly higher in patients with Crohn’s disease compared with patients with ulcerative colitis. Age, gender, disease activity, extent of disease and small bowel involvement each did not affect ASCA levels. The use of elemental or polymeric diet therapy for Crohn’s disease and administration of corticosteroids to patients with inflammatory bowel disease also did not affect ASCA levels. The ASCA titer was significantly lower in patients with Crohn’s disease taking mesalazine than in those not taking it, although, serum IgG levels did not differ between these two groups, which might imply a suppression of IgG production by mesalazine at the intestinal level.

Conclusions

The finding of increased serum ASCA titers in patients with inflammatory bowel disease suggests that Saccharomyces cerevisiae may play a role in the pathophysiology of this condition.
Efficacy of consensus interferon in the treatment of chronic hepatitis C
Authors: Kao Jia‐Horng , Chen Pei‐Jer , Lai Ming‐Yang , Chen Ding‐Shinn
Published: March 2003

Background and Aims

Consensus interferon (CIFN) is a newly developed type I interferon. The aim of this study was to investigate the safety and efficacy of CIFN in the treatment of patients with chronic hepatitis C and to determine the predictors for sustained response.

Methods

Patients were randomized to receive 3 μg or 9 μg CIFN three times a week for 24 weeks, followed by 24 weeks of observation. Efficacy was assessed by normalization of serum transaminase levels and disappearance of serum hepatitis C virus (HCV)‐RNA at the end of treatment and at 24 weeks after stopping treatment. Histologic response was defined as a decrease of at least two points in the Knodell necroinflammatory score at week 48 and was compared with baseline.

Results

There were no serious adverse effects related to CIFN therapy. Overall, 44% of patients receiving 3 μg and 48% of patients receiving 9 μg had normalization of serum transaminase levels and disappearance of HCV viremia at the end of treatment. At 24 weeks after stopping treatment, 16% of patients in receiving 9 μg and 12% of patients receiving 3 μg had sustained responses. The histologic responses in patients receiving 9 μg and those receiving 3 μg were 60% and 36%, respectively. The necroinflammatory score was significantly reduced from baseline to week 48 in both groups. In addition, bodyweight < 60 kg and pretreatment serum HCV‐RNA level < 0.5 MEq/mL can serve as predictors for sustained response to CIFN treatment.

Conclusions

These findings suggest that 9 μg CIFN is safe and effective in the treatment of patients with chronic hepatitis C.
Ranitidine‐related Stevens–Johnson syndrome in patients with severe liver diseases: A report of two cases
Authors: Lin Chen‐Chun , Wu Jaw‐Ching , Huang De‐Feng , Huang Yi‐Shin , Huang Yi‐Hsiang , Huo Teh‐Ia , Chang Full‐Young , Lee Shou‐Dong
Published: March 2003

Abstract Ranitidine is widely used and well tolerated. Ranitidine‐related skin eruption is rare and usually mild. We presented two patients who developed Stevens–Johnson syndrome after ranitidine therapy. Before therapy, both patients had severe liver disease and jaundice. The first was a case of ketoconazole‐induced hepatitis, and the second was a case of hepatitis C‐related liver cirrhosis with hepatocellular carcinoma. Ranitidine was the most likely drug responsible for causing Stevens–Johnson syndrome in these two patients.
‘Pseudo‐aldosteronism’ induced by intravenous glycyrrhizin treatment of chronic hepatitis C patients
Authors: Rossum Tekla GJ Van , De Jong Frank H , Hop Wim CJ , Boomsma Frans , Schalm Solko W
Published: March 2003

Background and Aims: Treatment with intravenous glycyrrhizin reduces the progression of liver disease caused by chronic hepatitis C (HCV) infection. Glycyrrhetinic acid, a metabolite of glycyrrhizin, inhibits the renal conversion of cortisol to cortisone by inhibiting the enzyme 11β‐hydroxysteroiddehydrogenase in the kidney. The resulting excess of cortisol subsequently stimulates the mineralocorticoid receptor, leading to pseudo‐aldosteronism with hypertension, hypokalemia and eventually renin and aldosterone suppression. The aim of this study was to evaluate the occurrence of pseudo‐aldosteronism after treatment of chronic hepatitis C (HCV) patients with increasing doses of intravenous glycyrrhizin.

Methods: Forty‐four HCV patients with chronic hepatitis or compensated cirrhosis were treated with intravenous glycyrrhizin 6 × 200 mg/week, 3 × 240 mg/week or 3 × 0 mg/week (placebo) for 4 weeks. In all patients, bodyweight, blood pressure and plasma concentrations of sodium, potassium, cortisol, DHEA‐S (dehydroepiandrosterone sulfate), renin and aldosterone were measured before, and at 0 and 4 weeks after treatment.

Results: Within the placebo group, no significant changes were observed. Within the 1200 mg group systolic blood pressure was significantly higher at the end of treatment, while aldosterone was significantly lower; at the end of the follow‐up period these values had returned to baseline. The changes from baseline in systolic and diastolic blood pressure at the end of treatment were significantly higher in the 1200 mg group compared to the placebo group. The changes in aldosterone and potassium concentrations at the end of treatment increased with increasing dosage, although not significantly.

Conclusion: Hepatitis C virus patients with chronic hepatitis or compensated cirrhosis show minor reversible symptoms of pseudo‐aldosteronism after treatment with 1200 mg glycyrrhizin weekly for 4 weeks.
Prevalence of hepatitis B or C virus infections in patients with non‐Hodgkin's lymphoma
Authors: Kuniyoshi Masami , Nakamuta Makoto , Sakai Hironori , Enjoji Munechika , Kinukawa Naoko , Kotoh Kazuhiro , Fukutomi Marie , Yokota Masaki , Nishi Hidehiro , Iwamoto Hiroaki , Uike Naokuni , Nishimura Junji , Inaba Shuichi , Maeda Yoshiaki , Nawata Hajime , Muta Koichiro
Published: March 2003

Background: Hepatitis C virus (HCV) and hepatitis B virus (HBV) are not only hepatotropic, but also lymphotropic viruses. Recently, some reports suggested that these viruses may participate in the development of malignant lymphoproliferative disorders.

Methods: We investigated the prevalence of HCV or HBV infection in 348 patients with non‐Hodgkin's lymphoma (NHL). We also compared these prevalences with those in blood donors as a control group representing the general population in our area (n = 1 513 358). Next, we evaluated the clinical and pathologic characteristics of HCV‐ or HBV‐infected NHL cases. Non‐Hodgkin's lymphoma was classified according to the Working Formulation classification.

Results: Thirty‐seven cases (14.9%) were found to be infected with HCV or HBV; of these, 20 (8.1%) were infected with HCV, and 17 (6.9%) with HBV. In male NHL patients, the rate of HCV infection was significantly higher than in an age‐ and sex‐matched population in the same area (P < 0.001, Mantel– Haenszel test). The rate of HBV infection also tended to be higher in the population (P = 0.0551). In contrast, in female NHL patients, the rate of HCV or HBV infection was not higher than in the general population. In HCV‐infected cases, 15 cases (75%) had B‐cell NHL and 16 cases (80%) were classified as being in the intermediate grade; B‐cell NHL comprised 83% of all NHL cases. In HBV‐infected NHL cases, 11 (65%) were of B‐cell type and 10 (58%) were classified as being in the intermediate grade.

Conclusions: The high prevalence of HCV or HBV infections in our study population provides epidemiologic evidence suggesting that HCV and HBV infections may be involved in the development of a subgroup of NHL in males. Our investigation also revealed that both HCV‐ and HBV‐infected NHL patients showed certain similarities in clinical and pathologic manifestations.
A case of autoimmune hepatitis with a high titer of antimitochondrial antibody and normal γ‐globulinemia
Authors: Shibata Minoru , Morizane Toshio , Tanaka Atsushi , Onozuka Yasushi , Uchida Toshikazu , Gershwin M Eric , Mitamura Keiji
Published: March 2003

Abstract We report here a patient with chronic active hepatitis who had no markers for hepatitis viruses and no hyper‐γ‐globulinemia, but had high titers of antimitochondrial antibody. Serum levels of alkaline phosphatase were normal, and antinuclear antibody, antismooth muscle antibody, and antiliver kidney microsome antibody tested negative. The titers of antimitochondrial antibody exceeded 1:640, and the positivity for anti‐M2 was ascertained by using both ELISA and immunoblot with beef‐heart mitochondria and a recombinant pyruvate dehydrogenase E2 subunit as antigens. This patient responded to ursodeoxycholic acid (UDCA) therapy in the beginning, but her hepatitis flared up during UDCA therapy. In contrast, she responded completely to corticosteroid therapy. The clinical course and histological findings of this patient strongly suggest that this patient has autoimmune hepatitis.
Treatment of hepatocellular carcinoma by percutaneous laser hyperthermia
Authors: Christophi Christopher , Muralidharan Vijayaragavan
Published: March 2003

Background and Aim: The majority of patients with hepatocellular carcinoma (HCC) are unsuitable for partial liver resection or transplantation because of unfavorable tumor characteristics or underlying severe liver disease. Techniques of in situ tumor ablation may be an alternative to resection and have the advantage of reduced morbidity and mortality. Percutaneous laser‐induced hyperthermia produces predictable areas of tumor necrosis with minimal complications. This study assesses the effectiveness of percutaneous interstitial laser hyperthermia in eight patients with hepatocellular carcinoma occurring on a background of chronic liver disease.

Methods: Patients with confirmed HCC with less than five tumor nodules of less than 7 cm maximum diameter were selected for treatment. Tumor response was monitored by dynamic CT, α‐fetoprotein levels and liver function tests. Patients were discharged within 24 h.

Results: There were six males and two females, with liver disease of Child–Pugh grade C in five, and grade B in the others. Two patients had tumor recurrence following previous segmental resection. Four had solitary lesions, and individual lesion size ranged between 3 and 7 cm. Avascularity and significant necrosis of the tumor was achieved on all lesions less than 4 cm, but was unsuccessful in tumors greater than 5 cm despite repeated treatments. Survival of patients ranged from 3 to 18 months.

Conclusions: Percutaneous laser hyperthermia produces significant tumor necrosis and has the advantage of low morbidity, and cost effectiveness. Further refinement is needed to achieve elimination of viable tumor cells at the tumor host interface by further knowledge of appropriate dosimetry levels, manipulation of blood flow and synergistic effects with other therapeutic modalities.
Effects and mechanisms of somatostatin analogs on apoptosis of pancreatic acinar cells in acute pancreatitis in mice
Authors: Yuan Yaozong , Gong Zihua , Lou Kaixian , Tu Shuiping , Di Zukang , Xu Jiayu
Published: March 2003

Aim:

To investigate the effects of somatostatin analogs (SSa) on apoptosis of pancreatic acinar cells and apoptosis‐regulated gene bax, and p53 in treating acute pancreatitis in mice.

Methods:

In cerulein‐induced pancreatitis, with or without treatment of somatostatin, analogs (Octreotide) in CD‐1 (BALB/c × DΒΑ/1) mice, apoptosis of pancreatic acinar cells was detected by using the TdT‐mediated dUTP nick‐end labeling (TUNEL) method, and the expression of apoptosis‐regulated gene bax and p53 was determined by using the streptavidin‐peroxidase immunohistochemical technique and the RT‐PCR method, respectively.

Results:

On HE staining, acinar cells in the pancreas showed pyknotic nuclei and the formation of apoptotic bodies, which are the typical morphological features of apoptosis. Regarding TUNEL use, the apoptotic index of pancreatic acinar cells in the non‐treated group at 5 and 14 h after induction of acute pancreatitis was significantly lower than those of the SSa‐treated group, respectively (P < 0.01). On immunohistochemistry and RT‐PCR, there was an expression of neither bax nor p53 in normal pancreatic tissues. The expression of bax in the SSa‐treated group at 5 and 14 h after treatment of SSa was markedly higher than those of the non‐treated group, respectively (P < 0.01), but there was no significant difference in the expression of p53 between the SSa‐treated group and the non‐treated group.

Conclusions:

The induction of apoptosis in pancreatic acinar cells injury to reduce inflammatory reaction might be one of the mechanisms of SSa in treating acute pancreatitis in mice, and the mechanisms of apoptosis probably correlated with the expression of apoptosis‐regulated gene bax, but have no relationship with the expression of p53.
Post‐partum acute exacerbation of chronic hepatitis in a hepatitis C‐carrier mother
Authors: Chen Jin‐De , Chung Jing‐Liang , Kao Jia‐Horng , Chen Ding‐Shinn
Published: March 2003

Hepatitis C virus infection is a global health problem; however, the interaction between pregnancy and chronic hepatitis C remains controversial. A Taiwanese woman with chronic hepatitis C had an uncomplicated pregnancy and gave birth to a female baby through spontaneous vaginal delivery. The serum levels of alanine aminotransferase and hepatitis C virus (HCV) RNA were measured before pregnancy, in the first and third trimesters, 1 and 3 months after delivery, respectively. During her pregnancy, the serum aminotransferase levels became normalized, while the serum HCV‐RNA levels declined significantly and consecutively with the lowest viral load in the third trimester. One month after delivery, she had an abrupt elevation of serum HCV‐RNA level, paralleling a hepatitis flare with serum aminotransferase level more than 20‐fold the upper normal limit. The serum HCV‐RNA levels declined thereafter, and serum aminotransferase levels became normalized 3 months postdelivery. She was infected with HCV genotype 1a throughout the entire follow‐up period, and other causes of hepatitis flare were excluded. In conclusion, post‐partum acute exacerbation of chronic hepatitis may occur in HCV‐carrier mothers, and an abrupt elevation of serum HCV‐RNA level may be associated with the acute exacerbation.
Current perspectives in gallbladder carcinoma
Authors: Kaushik Satyendra P
Published: March 2003

Abstract Carcinoma gallbladder (CaGB) is not a common malignancy in a large number of countries in the world, except Chile, Japan, some parts of India, and a few other regions. Lacunae exist even today in terms of understanding of its epidemiology, aetiopathogenesis, and in the early pick up of malignanacy, as well as in choosing the most appropriate treatment option for a given case. While Japanese surgeons have advocated radical resections for CaGB and have shown good outcome resulting in long‐ term survival, others have not felt convinced about the desirability of undertaking such morbid surgical procedures in all patients. Also, radical resections have not always resulted in a tumor‐free state and a cure in a large percentage of cases. Under the circumstances, the clinician's mind is often confused as to the most beneficial option for that patient once curative resection is not possible. Palliation of the jaundice and/or gastric outlet obstruction relieves the symptoms but does not prolong survival. The role of adjuvant chemotherapy with or without cytoreductive surgery has not been fully explored in CaGB. The present review quotes experience that seems to support the above contention. However, a number of well‐designed multicentric trials are required to confirm the above philosophy of treatment for the benefit of patients suffering from CaGB.
Enhancement of tumor radioresponse by combined chemotherapy in murine hepatocarcinoma1
Authors: Seong Jinsil , Kim Sung Hee , Suh Chang OK
Published: March 2003

Background and Aims: Recent studies have shown that local radiotherapy can be an effective component of the treatment for hepatocellular carcinoma. To further improve therapeutic efficacy, use of drugs that can beneficially interact with radiation has been suggested. The purpose of this study was to identify drugs that can enhance radioresponse of murine hepatocarcinoma.

Methods: C3H/HeJ mice bearing 8 mm tumors of murine hepatocarcinoma, HCa‐I, were treated with 25 Gy radiation and one of the following drugs: 5‐Fu, 150 mg/kg; adriamycin, 8 mg/kg; cisplatin, 6 mg/kg; paclitaxel, 40 mg/kg; and gemcitabine, 50 mg/kg. Tumor response to the treatment was determined by the use of a tumor growth delay assay and by an enhancement factor. The apoptotic level was assessed in tissue sections. The expression of regulating molecules was analyzed by using western blotting for p53, Bcl‐2, Bax, Bcl‐XL, Bcl‐XS, and p21WAF1/CIP1.

Results: Among the drugs tested, only gemcitabine enhanced the antitumor effect of radiation, with an enhancement factor of 1.6. The induction of apoptosis by a combination of gemcitabine and radiation was shown as only an additive level. In the analysis of radiation‐induced expression of regulating molecules, the most significant change by combining gemcitabine with radiation was the activation of p21WAF1/CIP1.

Conclusion: Gemcitabine is the first to show an enhancement of radioresponse of murine hepatocarcinoma when combined with radiation. The key element of enhancement is thought to be p21WAF1/CIP1.
Alterations of telomerase activity and terminal restriction fragment in gastric cancer and its premalignant lesions
Authors: Yang Shi‐Ming , Fang Dian‐Chun , Luo Yuan‐Hui , Lu Rong , Battle Paul D , Liu Wei‐Wen
Published: March 2003

Aims: In order to explore the role of alterations of telomerase activity and terminal restriction fragment (TRF) length in the development and progression of gastric cancer.

Methods: Telomerase activity was detected in 176 specimens of gastric mucosa obtained through an operation or endoscopical biopsy by using the telomeric repeat amplification protocol (TRAP) assay. Meanwhile, the mean length of TRF was measured with the use of a Southern blot in part of those samples.

Results: Telomerase activity was detected in 14 of 57 (24.6%) chronic atrophy gastritis patients, six of 18 (33.3%) intestinal metaplasia patients, three of eight (37.5%) dysplasia patients and 60 of 65 (92.3%) gastric cancer patients, respectively. Normal gastric mucosa revealed no telomerase activity. No association was found between telomerase activity and any clinicopathological parameters. The mean TRF length was decreased gradually with age in normal mucosa and in gastric cancer tissue. Regression analysis demonstrated that the reduction rate in these tissues was 41 ± 12 base pairs/year. Among 35 gastric cancers, TRF length was shown to be shorter in 20 cases (57.1%), similar in 12 cases (34.3%) and elongated in three cases (7.6%), compared to the corresponding adjacent tissues. The mean TRF length tended to decrease as the mucosa underwent chronic atrophy gastritis, intestinal metaplasia, dysplasia and into gastric cancer. The mean TRF length in gastric cancer was not statistically correlated with clinicopathological parameters and telomerase activity.

Conclusions: Our results suggest that telomerase is expressed during the early stage of gastric carcinogenesis, and that the clinical significance of TRF length appears to be limited in gastric cancer.
Expression of B7 costimulatory molecules by cells infiltrating the colon in experimental colitis induced by oral dextran sulfate sodium in the mouse
Authors: Grose Randall H , Howarth Gordon S , Xian Cory J , Hohmann Arthur W
Published: March 2003

Background and Aim:

T‐cell activation, mediated by the interaction with major histocompatibility complex (MHC)‐peptide complexes and B7 costimulatory molecules on antigen‐presenting cells, is an essential event in the pathogenesis of inflammatory bowel disease (IBD). We investigated the expression of B7 costimulatory molecules on cells in the colon in an experimental mouse model of IBD to determine whether the B7/ligand interaction could provide a target for therapeutic intervention in IBD.

Methods:

Experimental colitis was induced in mice by oral consumption of water substituted with 5% dextran sulfate sodium (DSS). Mice (n = 4) were killed 1, 2, 3, 4 and 7 days after commencing DSS consumption, and colonic tissue was collected and examined immunohistochemically for T cells, B cells, macrophages and cells expressing B7‐1 or B7‐2.

Results:

Compared to control mice drinking water, macrophage numbers in the colonic epithelium were elevated sevenfold by day 1 and T cells were elevated threefold by day 3 following commencement of DSS consumption. Numbers of infiltrating B7‐positive (B7+) cells were not significantly elevated until day 7 when B7‐1+, B7‐2+ cells and macrophages were increased 20‐fold compared to normal mice.

Conclusion:

These results demonstrate that an initial and rapid infiltration of the colonic epithelium by B7‐negative macrophages is followed by an infiltration of T cells and subsequent upregulation of the B7 costimulatory molecules potentiating the inflammatory reaction in this disease model. These results suggest an intervention strategy based on the blockade of the B7‐costimulatory axis could find application in the treatment of inflammatory bowel disease.
Synchronous triple cancers at middle and lower esophagus and stomach with different histological features and genetic alterations
Authors: CHANG YU‐TING , TSAI CHUN‐I , YANG TZENG‐HUEY , SHIH CHIA‐WEN , WU MING‐SHIANG , LIN JAW‐TOWN
Published: March 2003

Synchronous multiple primary malignancies are relatively unusual. We describe a case of synchronous triple cancers located at the middle and lower esophagus and the stomach in a 59‐year‐old Taiwanese man who presented with progressive dysphagia, epigastralgia, and bodyweight loss in 1 month. Endoscopic and histological features, microsatellite instability status of genomic DNA, and immunohistochemical staining of p53, MUC2, Fhit, c‐erbB‐2 and E‐cadherin of all three cancers were demonstrated. We noted that these three cancers arose from different clones and that p53 mutation, instead of microsatellite instability, may play a major role in the development of multiple primary malignancies in this patient.
Fas (Apo‐1/CD95) and Fas ligand interaction between gastric cancer cells and immune cells
Authors: LEE TAE‐BUM , MIN YOUNG‐DON , LIM SUNG‐CHUL , KIM KYUNG‐JONG , JEON HO‐JONG , CHOI SEOK‐MIN , CHOI CHEOL‐HEE
Published: March 2003

Background and aims: It has been proposed that the expression of Fas ligand (Fas L) in tumors may play an important role in immune escape. This study was undertaken to test a ‘counterattack’ theory as a mechanism of immune escape in gastric carcinoma.

Methods: Expression of Fas and Fas L was examined in the human gastric cancer cell lines

using reverse transcription–polymerase chain reaction. Cytotoxicity was determined

by the MTT [3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide] assay.

Apoptosis of target Jurkat cells was examined after coculture with the effector gastric

cancer cells in vitro. Immunohistochemical staining was performed for the

detection of Fas and FasL in tumor‐infiltrating lymphocytes (TIL) and gastric cancer

cells in vivo. Apoptosis was detected by terminal deoxynucleotidyl transferase

(TdT)‐mediated dUTP nick‐end labeling (TUNEL) method in vitro and in vivo.

Results: Fas and FasL mRNA were found to be differentially expressed in gastric cancer cell lines. The coculture experiment showed that apoptosis of Jurkat was induced by a FasL‐overexpressing effector gastric cell SNU‐484. In a Fas‐expressing gastric cell SNU‐638, Fas expression was upregulated by the treatment of gamma‐interferon in a time‐ and concentration‐dependent manner. SNU‐638 treated with gamma‐interferon was more sensitive to anti‐Fas antibody‐mediated cytotoxicity than was the control cell line, suggesting an increase of functional Fas in gastric cancer cells. The expression of FasL in gastric cancer cells and of Fas in apoptotic TIL was also detected in

vivo.

Conclusion: The data indicate that the FasL expression of gastric cancer cells supports a ‘counterattack

theory’ in gastric cancer cells and that the upregulation of Fas by IFN‐γ

in SNU‐638 may accelerate the apoptosis pathway through the Fas and FasL interaction

between gastric cancer cells and immune cells. This result is supported by the expression

of FasL in gastric cancer cells and apoptotic TIL in vivo. It is implicated that the different biological behaviors of gastric cancer cells could be at least in part explained by Fas and FasL interaction with immune cells.
Automated enzymatic mitochondrial antibody assay for the diagnosis of primary biliary cirrhosis: Applications of a routine diagnostic tool for the detection of antimitochondrial antibodies
Authors: HAZAMA HIROAKI , OMAGARI KATSUHISA , MASUDA JUN‐ICHI , OHBA KAZUO , KINOSHITA HIDEKI , MATSUO ISAO , ISOMOTO HAJIME , MIZUTA YOHEI , MURASE KUNIHIKO , MURATA IKUO , KOHNO SHIGERU
Published: March 2003

Background and Aims: An automated enzymatic mitochondrial antibody assay (EMA) kit for the diagnosis of primary biliary cirrhosis (PBC) has become commercially available recently. The aim of this study was to assess the clinical utility of the enzyme inhibition assay using this EMA kit for the diagnosis of PBC.

Methods: We tested the immunoreactivity of sera from 54 histologically confirmed Japanese PBC patients to the 2‐oxo‐acid dehydrogenase complex (2‐OADC) enzymes by enzyme inhibition assay using commercially available TRACE (EMA) assay kit, and compared the results with those of indirect immunofluorescence, commercial enzyme‐linked immunosorbent assay (ELISA) using MESACUP Mitochondria M2 kit, and immunoblotting on bovine heart mitochondria.

Results: Of the 54 sera, 43 (80%) were positive for antimitochondrial antibodies
(AMA) by immunofluorescence, 39 (72%) for enzymatic inhibitory antibody to
pyruvate dehydrogenase complex (PDC) by EMA, 33 (61%) for immunoglobulin
G (IgG) class anti‐PDC antibody by ELISA, and 53 (98%) for IgG, IgM, or IgA
class antibodies against at least one of the 2‐OADC enzymes by immunoblotting. Of
these, 43 (80%) were positive for IgG, IgM, or IgA class antibodies against
the E2 subunit of PDC (PDC‐E2) by immunoblotting. Thirty‐six of the 54 sera (67%)
showed identical results in all of the four assays, and 40 (74%) were all
negative or positive by EMA, ELISA, and immunoblotting in PDC‐relevant reactivity.
There was a significant correlation between the number of detected immunoglobulin
classes of anti‐PDC‐E2 by immunoblotting and anti‐PDC by EMA (P < 0.0001),
and a significant inverse correlation between IgG class anti‐PDC by ELISA and units
of PDC activity by EMA (r = −0.87, P < 0.0001).

Conclusions: Although EMA had lower sensitivity compared with immunofluorescence and immunoblotting, this assay should be included among the routine diagnostic tools for the detection of AMA specific to PBC in clinical laboratories because of its high specificity, objective read‐out, and rapid turnaround time.

© 2002 Blackwell Science Asia Pty Ltd