bluuebunny/crossref_metadata_2025 huggingface dataset:
Accumulation of copper in the liver and hepatic injury in chronic hepatitis C
Authors: Hatano Ryoji , Ebara Masaaki , Fukuda Hiroyuki , Yoshikawa Masaharu , Sugiura Nobuyuki , Kondo Fukuo , Yukawa Masae , Saisho Hiromitsu
Published: March 2003

Background and Aims
: Relationships between chronic liver disease and trace metals have not been clearly understood. To examine connections between severity of hepatic fibrosis in chronic hepatitis C and copper, iron and zinc we measured the contents of these metals in liver tissue and serum in the patients.

Methods
: Forty‐one patients (26–62 years), 13 with fibrosis representing grade F1, 16 with F2, seven with F3, and five with F4, entered this study. Metals were quantified in needle liver‐biopsy specimens by particle‐induced X‐ray emission. In serum, metals were measured by flameless atomic absorption spectrometry.

Results
: Hepatic copper content increased with progression of hepatic fibrosis (P < 0.05). The copper content correlated positively with bilirubin (r = 0.466, P = 0.0023), and with type IV collagen (r = 0.402, P = 0.0086) and correlated negatively with albumin (r = – 0.404, P = 0.080). However, hepatic iron and zinc contents did not show a significant differences between grades of fibrosis.

Conclusions
: Copper accumulation in fibrotic livers caused by chronic hepatitis C may contribute to hepatic injury. The real mechanism is not known at present, but excess copper may damage the liver by oxidative stress.
Role of neutrophils in sinusoidal endothelial cell injury after extensive hepatectomy in cholestatic rats
Authors: Ohtsuka Masayuki , Miyazaki Masaru , Kubosawa Hitoshi , Kondo Yoichiro , Ito Hiroshi , Shimizu Hiroaki , Shimizu Yoshiaki , Nozawa Satoshi , Furuya Seiji , Nakajima Nobuyuki
Published: March 2003

Background and Aims
: The authors have shown previously that sinusoidal endothelial cell injury developed concomitantly with the accumulation of neutrophils in the hepatic sinusoidal space in cholestatic rats after extensive hepatectomy. The aim of the present study was to investigate the role of neutrophils in the development of this kind of endothelial cell injury.

Methods
: Rats underwent 78% partial hepatectomy after 2 weeks of cholestasis, and subsequent external biliary drainage for 5 days. To decrease the number of neutrophils, antirat neutrophil serum was administered intraperitoneally. Some serum parameters and histological specimens were examined 48 h after partial hepatectomy.

Results
: Anti‐neutrophil serum significantly reduced the number of accumulated neutrophils in the hepatic sinusoids. Although the purine nucleoside phosphorylase : alanine aminotransferase ratio, a marker of non‐parenchymal cell injury, was increased in cholestatic‐hepatectomized rats, this abnormality was significantly attenuated by the treatment with antineutrophil serum. Electron microscopically, focal detachment of cytoplasms of sinusoidal endothelial cells was observed occasionally in cholestatic‐hepatectomized rats, but was not found in the antirat neutrophil serum‐treated rats.

Conclusion
: These results indicate that accumulated neutrophils might be important effector cells in the pathogenesis of sinusoidal endothelial cell injury after extensive hepatectomy in cholestatic rats, even after appropriate external biliary drainage.
Patients with stable uncomplicated cirrhosis have normal neutrophil function
Authors: Kirsch Richard , Woodburne Vivienne E , Shephard Enid G , Kirsch Ralph E
Published: March 2003

Background: Neutrophil function has been reported to be abnormal in patients with cirrhosis. In order to evaluate the relative contribution of hepatocellular dysfunction and portalsystemic shunting of blood to these abnormalities, neutrophil function was studied in 18 patients with cirrhosis and portal hypertension. Nine patients, with extrahepatic portal hypertension (EPH) caused by portal vein thrombosis, who had no clinical, biochemical or histologic evidence of liver disease were also studied.

Methods: Superoxide generation, phagocytosis, degranulation, leukotriene B4 release, candidacidal activity and quantitative and qualitative expression of the cell surface adhesive marker CD11b/CD18 were measured in these patients as well as in age‐ and gender‐matched controls.

Results: Patients with cirrhosis were found to have a small but statistically significant decrease in the expression of the CD18 component of MAC1 in N‐formyl‐methionyl‐leucyl‐phenylalanine‐stimulated neutrophils (P = 0.04). No significant differences were found between either of the two patient groups and the control group for any of the other parameters of neutrophil function tested.

Conclusions: These were unexpected findings in the light of data published elsewhere, which indicate impaired neutrophil function in patients with cirrhosis. The study suggests that patients with stable, uncomplicated cirrhosis and patients with EPH have normal neutrophil function.
Outcomes of primary hepatocellular carcinoma treatment: An 8‐year experience with 368 patients in Thailand
Authors: Pawarode Attaphol , Tangkijvanich Pisit , Voravud Narin
Published: March 2003

Background and Aims
: Primary hepatocellular carcinoma (HCC) is common in Thailand and its prognosis is extremely poor. Hepatic resection and liver transplantation are modes of curative therapy and various therapies have been developed to treat inoperable HCC. This study was performed to determine the outcome of therapy and to identify prognostic factors for survival among Thai patients with HCC.

Methods
: Three hundred and sixty‐eight patients with tissue‐proven or serodiagnosed HCC were studied. Differences in laboratory investigations, patient survival, treatment outcomes and prognostic factors were analysed. The Kaplan–Meier method and the log‐rank test were used to calculate and compare survival of patients receiving different therapies.

Results
: Of the 368 patients 317 were males (86.1%, M : F ratio 6.2 : 1). The median age of all patients was 52 years range (2–85 years). Fifty‐nine patients were specifically treated and 209 were conservatively treated. Among those tested, 70% had hepatitis B virus‐related HCC. The overall median survival (range) after diagnosis and that of the treated and untreated patients were 5.6 (0–92.1), 9.0 (0–92.1) and 2.3 (0–25.9) months, respectively. More than 50% of the Okuda I patients survived beyond 30 months. The Okuda II and III patients had a median survival (range) of 5.7 (0.1–75.2) and 1.6 (0.1–25.9) months, respectively. Those patients treated by surgery, transcatheter oil chemoembolization and systemic chemotherapy had a better survival rate than did the conservatively managed patients. Surgery was found to be a better treatment than systemic chemotherapy. However, no differences between other pairs of treatment groups were identified. Subgroup analysis of the Okuda II group patients revealed the same results. Independent predictors of death were multiple lesions, advanced Okuda stage and treatment modality.

Conclusion
: Despite various kinds of therapy, the treatment outcomes for Thai HCC patients remain poor and largely depend on the disease extent and treatment received. Most Thai HCC patients are at an advanced stage at diagnosis. Thai patients who received disease‐specific treatment other than intra‐arterial chemotherapy had a better survival rate than did supportive treatment patients.
Inhibition of mitogen‐induced murine lymphocyte proliferation by Helicobacter pylori cell‐free extract
Authors: Chen Wangxue , Shu Dairu , Chadwick Vinton S
Published: March 2003

Background and Aims
: Previous studies have shown that lysates of Helicobacter pylori inhibit mitogen‐induced proliferation of human peripheral blood mononuclear cells. The objective of the present study was to determine whether H. pylori cell‐free extract (HPCE) has similar effects on murine lymphoid cells and could, therefore, be used to further delineate the mechanisms of alteration of lymphocyte function by H. pylori.

Methods
: The HPCE was prepared from a H. pylori reference strain and from five clinical strains with varying status of cagA and vacA. Mouse splenic and mesenteric lymph node cells were cultured in microwell plates in the presence or absence of varying concentrations of HPCE (0.625–12.5 μg/mL). T cell mitogens were added into the culture 2 h later and the cells were cultured at 37°C in 5% CO2 for a further 72 h. Cell proliferation was determined by a non‐radioactive rapid dye assay and the percentage inhibition caused by HPCE was calculated.

Results
: Pre‐exposure to HPCE significantly inhibited concanavalin A‐induced proliferation of murine spleen and mesenteric lymph node cells (up to 100% inhibition; P≤ 0.01). The HPCE also inhibited lymphocyte proliferation stimulated by mitogens phorbol‐myristate‐acetate and ionomycin and by the anti‐CD3ɛ monoclonal antibody (P≤ 0.05). The inhibition was dose‐dependent, but independent of the presence of virulence genes cagA or vacA. Treatment of HPCE at 80°C for 30 min, but not at 55°C for 60 min, completely abolished its inhibitory action. The HPCE, pretreated with pronase E, proteinase K, trypsin, acid or alkali also completely lost its inhibitory effect (P≤ 0.01), while in contrast, treatment with carboxypeptidase and leucine aminopeptidase had no effect.

Conclusion
: Helicobacter pylori produces heat‐labile proteins or peptides that suppress T cell mitogen‐induced proliferation of murine lymphoid cells in a similar manner to that observed with human peripheral blood mononuclear cells. The mouse cell culture system can, therefore, be used as a model to further study the mechanisms of action and antigen specificity of these immunomodulatory factors.
Prevention of proteolysis in cold‐stored rat liver by addition of amino acids to the preservation solution
Authors: Charrueau Christine , Blondé‐Cynober Françoise , Coudray‐Lucas Colette , Poupon Raoul , Chaumeil Jean‐Claude , Hannoun Laurent , Cynober Luc
Published: March 2003

Abstract Background: One process identified as detrimental in liver preservation is proteolysis.

Methods: We tested the effects of adding antiproteolytic amino acids (L‐alanine, L‐glutamine, L‐histidine, L‐leucine, L‐methionine, L‐phenylalanine, L‐proline, L‐tryptophan) to the preservation medium, in a model of reperfusion of 24 h cold‐stored rat livers.

Results: During the preservation period, antiproteolytic amino acids inhibited the proteolysis observed in stored livers as shown by branched‐chain amino acid fluxes, which switched from release to uptake. During reperfusion, cold storage of lives without the addition of antiproteolytic amino acids resulted in a decrease in the total amino acid and branched‐chain amino acid uptake and a lower perfusion flow rate. The addition of antiproteolytic amino acids during liver storage resulted in the maintenance of total amino acid and branched‐chain amino acid uptake and a significant improvement in the perfusion flow rate during reperfusion.

Conclusions: The presence of antiproteolytic amino acids in the preservation medium might be of interest in improving hepatic graft viability in transplantation.
Troglitazone prevents fatty changes of the liver in obese diabetic rats
Authors: Jia Dong Mei , Tabaru Akinari , Akiyama Toshiharu , Abe Shintaro , Otsuki Makoto
Published: March 2003

AbstractBackground and Aims:Troglitazone is a newly developed antidiabetic drug and is indicated to be useful for the treatment of patients with type II diabetes mellitus. Recently, however, it became clear that troglitazone could cause liver dysfunction in some patients. In addition, a relationship between the activation of the peroxisome proliferator‐activated receptor gamma receptor by troglitazone and colon tumorigenesis has been suggested. The present study was undertaken to examine the effects of long‐term administration of troglitazone on the liver and intestine in genetically obese and diabetic Otsuka Long‐Evans Tokushima Fatty (OLETF) and control Long‐Evans Tokushima Otsuka (LETO) rats.

Methods:A troglitazone‐rich diet (200 mg/100 g normal chow) or a standard rat chow, free of troglitazone (control), was given to OLETF and LETO rats from 12 or 28 weeks of age until 72 weeks of age. Serum levels of glucose, insulin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were determined at several time points. In addition, histology of the liver and intestine and serum levels of cholesterol and triglycerides were examined at 72 weeks of age.

Results:Troglitazone prevented age‐related increases in fasting glucose and insulin concentrations in OLETF rats, but had no significant influences on serum levels of AST and ALT in both strains of rats. The liver weights in the control OLETF rats were significantly heavier than in the LETO rats. Troglitazone significantly reduced serum cholesterol and triglyceride levels and the liver weight. However, it had no influence on the large intestine weight and the number of colonic polyps in both OLETF and LETO rats. Sections of the liver from the untreated OLETF rats showed mild fatty changes in the central zone of the hepatic lobule, whereas those from the troglitazone‐treated OLETF rats appeared normal with no fat deposition in the hepatocytes. Troglitazone in LETO rats also caused no significant histopathologic changes of the liver tissue.

Conclusion:Our present study demonstrated that long‐term administration of troglitazone prevents the progress of the metabolic derangement and fatty changes of the liver in genetically determined obese diabetes.
Expandable metallic stents should not be used in the treatment of benign esophageal strictures
Authors: Ackroyd Roger , Watson David I , Devitt Peter G , Jamieson Glyn G
Published: March 2003

Abstract Expandable metallic stents have become popular in recent years for the treatment of esophageal strictures. While they are undoubtedly of great value in the palliation of malignant strictures and tracheo‐esophageal fistulas, there is concern over their use for the treatment of benign diseases. We report three cases, in which such problems were seen following stent insertion for benign esophageal strictures. All three patients developed further strictures above the stents, one was complicated by a tracheo‐esophageal fistula and two stents (in one patient) migrated distally into the stomach. Two of the patients underwent subsequent esophageal surgery. In both cases, this proved extremely difficult and hazardous because of the intense fibrotic reaction induced by the stents. Expandable mesh stents should not be used for the treatment of benign esophageal strictures without careful consideration of the potential problems, which can include rendering the problem inoperable.
Evaluation of pancreatic secretion after administration of secretin: Application of magnetic resonance imaging
Authors: Nanashima Atsushi , Yamaguchi Hiroyuki , Fukuda Toshio , Sakamoto Ichiro , Kuroda Akinori , Sawai Terumitsu , Nakagoe Tohru , Ayabe Hiroyoshi
Published: March 2003

Background: To evaluate pancreatic exocrine function, we measured the changes in T2 enhanced hydrograhic intensity on magnetic resonance (MR) images of the pancreas following an injection of secretin, which is representative of the changes in duodenal fluid volume.

Methods: The subjects were 10 patients with normal pancreatic function (N > 70% detected by using a pancreatic function diagnostant test) and 12 patients with hypo‐function, including those with mild hypo‐function (MH, 50–70%, six patients) and severe hypo‐function (SH < 50%, six patients).

Results: In the N group, T2 enhanced intensity of the pancreas increased to a maximum value (more than 10% compared with baseline) within 5 min of stimulation, then gradually decreased. No significant difference in the response was observed between the head and body of the pancreas. Changes in the MH group were similar to those of the N group. In contrast, significantly lower changes in T2 enhanced intensity were observed in SH group, relative to both the N and MH group (P < 0.05). The amount of secretin‐induced increase in duodenal fluid after 16 min was not significantly different among the three groups. Furthermore, an evaluation of the residual pancreatic tissue after a pancreatoduodenectomy was also feasible.

Conclusions: Our results indicate that the MR‐secretin test is useful for the evaluation of severe pancreatic exocrine dysfunction. The diagnostic test is simple, direct and non‐invasive.
A phase one study of the hepatic arterial administration of 1,25‐dihydroxyvitamin D3 for liver cancers
Authors: Finlay Ian G , Stewart Graham J , Ahkter Javed , Morris David L
Published: March 2003

Background and Aims: It is well established that exposure to 1,25‐dihydroxyvitamin D3 (1,25(OH)2D3) inhibits the proliferation of human colorectal cancer and hepatoma cell lines, both in vitro and in vivo. However, clinical trials of the administration of 1,25(OH)2D3 and analogs for the treatment of malignancy have been limited by the development of hypercalcemia. 1,25‐dihydroxyvitamin D3 is principally excreted in bile following hepatic catabolism. This suggested the hypothesis that hepatic regional administration may allow high doses of 1,25(OH)2D3 to be administered for the treatment of liver cancers without producing hypercalcemia, caused by a clinically significant first pass effect. This phase one study investigates the effect of hepatic regional administration of 1,25(OH)2D3 on serum calcium levels, together with other markers of renal and liver function.

Methods: Six subjects with hepatic colorectal cancer metastases and one with primary hepatocellular cancer were given continuous hepatic arterial infusions of 1,25(OH)2D3, for periods of 1–4 weeks. Blood samples were taken regularly and assayed for calcium levels, liver function tests and urea and electrolyte levels.

Results: Patients remained normocalcemic at dosages of up to 10 mcg/day. No patient experienced any side‐effects from the treatment.

Conclusions: Administration of 1,25(OH)2D3 as a continuous hepatic arterial infusion allows a high dosage to be administered without inducing hypercalcemia. This route of administration may allow the potential of 1,25(OH)2D3 in the treatment of hepatic cancers to be realized.
Imaging and clinical characteristics of focal atrophy of segments 2 and 3 in primary sclerosing cholangitis
Authors: Caldwell Stephen H , Hespenheide Elizabeth E , Harris Danielle , De Lange Eduard E
Published: March 2003

Background and Aims: Focal atrophy in primary sclerosing cholangitis (PSC) is usually thought to result from severe biliary stricture and focal biliary cirrhosis. Atrophy of the left lateral segments (segments 2 and 3) are striking when observed grossly. This type of atrophy may be subtle on cross‐sectional imaging and by endoscopic retrograde cholangiopancreatography (ERCP) because of the peripheral location and compensatory hypertrophy of other parts of the liver. We examined 44 consecutive PSC patients to determine the incidence and clinical characteristics of this abnormality, and to correlate imaging studies with the gross appearance.

Methods: We reviewed all cases of PSC encountered over a 3 year period ascertained from the liver disease registry. Magnetic resonance imaging or CT images were re‐examined for evidence of segment 2 and 3 atrophy.

Results: Four of 44 patients had focal segment 2 and 3 atrophy. These four had been confirmed laparoscopically or by inspection of the liver explant. The remaining segments of the liver were relatively spared of injury in two of the patients, and three of the four patients had preserved synthetic function without evidence of portal hypertension. While the abnormality is clearly visible on cross‐sectional imaging, its peripheral location caused it to be an unobtrusive. Likewise, ERCP did not clearly reveal the abnormality on initial inspection.

Conclusions: We conclude that focal atrophy of segments 2 and 3 is a sometimes early and subtle finding in PSC that may be overlooked in cross‐sectional imaging or ERCP unless specifically sought.
Radioisotope scintigraphy in the diagnosis of hepatic hydrothorax
Authors: Bhattacharya Anish , Mittal Bhagwant Rai , Biswas Tapas , Dhiman Radha Krishan , Singh Baljinder , Jindal Surinder Kumar , Chawla Yogesh
Published: March 2003

Background: Pleural effusion in cirrhotic patients (hepatic hydrothorax) may result from migration of ascitic fluid across defects in the diaphragm. Biochemical analysis of ascitic and pleural fluid provides only indirect information about the nature and origin of the effusion. The present study was performed in order to demonstrate the presence/absence of peritoneo–pleural communication by radioisotope imaging.

Methods: Ten patients with cirrhotic ascites and pleural effusion were studied with 99mTc sulfur colloid scintigraphy to look for movement of the radiotracer from the peritoneal to the pleural cavity. Serum–ascitic albumin gradient (SAAG) and serum–pleural fluid albumin gradient (SPAG) values were determined in eight patients to examine the nature of the ascitic and pleural fluids.

Results: Transdiaphragmatic movement of ascitic fluid into the pleural space was demonstrated (generally within 2 h of intraperitoneal injection of the radiotracer) in eight of 10 patients; six on the right side, one on the left and one bilaterally. Two patients in whom pleural fluid was transudative on SPAG values were negative for peritoneo–pleural communications.

Conclusions: Radionuclide scintigraphy is a simple, safe and relatively non‐invasive method to confirm passage of ascitic fluid across the diaphragm.
Cerebral vascular resistance assessed by transcranial color Doppler ultrasonography in patients with chronic liver diseases
Authors: Kawakami Manri , Koda Masahiko , Murawaki Yoshikazu , Kawasaki Hironaka , Ikawa Shiro
Published: March 2003

Background and Aim: Cerebral hemodynamic derangement is well known in patients with liver cirrhosis. The advent of transcranial Doppler enables a non‐invasive observation of cerebral hemodynamics. To evaluate the clinical usefulness we examined cross‐sectionally and longitudinally cerebral hemodynamic parameters in patients with cirrhosis.

Methods: The subjects of the cross‐sectional study were 117 patients with cirrhosis, 15 patients with chronic hepatitis and 25 healthy controls. The longitudinal study included 26 cirrhotic patients without encephalopathy, and 27 cirrhotic patients with encephalopathy. The pulsatility and resistive indices of the right middle cerebral artery were used as parameters of cerebral hemodynamics.

Results: Cerebral pulsatility and resistive indices were significantly higher in patients with cirrhosis (1.05 ± 0.23, P < 0.0001 and 0.63 ± 0.07, P < 0.0001, respectively) than in the controls (0.75 ± 0.11 and 0.55 ± 0.05, respectively) and patients with chronic hepatitis (0.81 ± 0.11 and 0.52 ± 0.05, respectively). Cerebral pulsatility and resistive indices were significantly related with the severity of liver cirrhosis. Patients with encephalopathy had higher cerebral pulsatility and resistive indices than patients without encephalopathy. In the longitudinal studies, cerebral pulsatility and resistive indices were changed in parallel with the severity of cirrhosis and encephalopathy. Cerebral pulsatility and resistive indices were significantly correlated with the blood ammonia level and serum levels of bilirubin and albumin.

Conclusion: These cross‐sectional and longitudinal studies showed that cerebral vascular resistance indices measured by using transcranial Doppler were increased in association with the severity of cirrhosis and encephalopathy. Cerebral pulsatility and resistive indices are real‐time and useful parameters to assess and monitor cirrhotic patients.
High viral loads, serum alanine aminotransferase and gender are predictive factors for the development of hepatocellular carcinoma from viral compensated liver cirrhosis
Authors: Ishikawa Toru , Ichida Takafumi , Yamagiwa Satoshi , Sugahara Satoshi , Uehara Kazuhiro , Okoshi Shogo , Asakura Hitoshi
Published: March 2003

Background and Aims:

The aims of the present study were to determine the occurrence rate of hepatocellular carcinoma (HCC) and to assess the risk factors for the development of HCC in compensated viral liver cirrhosis.

Methods:

Two hundred and thirty‐nine cirrhotic patients (65 hepatitis B surface antigen (HBsAg) positive, 165 hepatitis C virus (HCV) antibody positive (anti‐HCV), and nine with both HBsAg and anti‐HCV positivity) were studied. The Kaplan–Meier method evaluated by a log–rank test was used to estimate the cumulative probability of HCC development. Independent predictors of HCC development were estimated by using the Cox proportional hazard regression analysis.

Results:

Dual infection manifested as HBsAg and anti‐HCV positive was the highest risk of HCC. Multivariate analysis indicated that anti‐HCV positive, HBsAg positive, and lactate dehydrogenase were independent predictors of the development of HCC among individuals with viral cirrhosis. In the HBsAg‐positive group, a high‐titer of HBV‐DNA (more than 3.7 log genome equivalents (LGE)/mL) was most predictive of HCC development. In the anti‐HCV‐positive group, male gender and a high‐titer of HCV‐RNA (more than 1.0 Meq/mL) were predictive factors for the development of HCC.

Conclusions:

Individuals with high viral loads should be monitored for the development of HCC. Clinical efforts at eradicating or reducing the viral load may reduce the risk for HCC.
A case of Behçet’s disease accompanied by colitis with longitudinal ulcers and granuloma
Authors: NAGANUMA MAKOTO , IWAO YASUSHI , KASHIWAGI KAZUHIRO , FUNAKOSHI SHINSUKE , ISHII HIROMASA , HIBI TOSHIFUMI
Published: March 2003

A 37‐year‐old female presenting with oral and genital ulcers and erythema nodosum on both arms was diagnosed as having Behçet’s disease. The symptoms resolved spontaneously. However, she was admitted to our hospital (Keio University Hospital) several months later because of fever, aphthous ulcers of the oral cavity, lower abdominal pain and frequent diarrhea. A colonoscopic examination revealed multiple ulcers including longitudinal ulcers in the ascending and transverse colon, and histological examination of biopsied specimens demonstrated non‐caseating epithelioid granuloma. Treatment with prednisolone and 5‐aminosalicylic acid was started, and the patient responded well clinically. One month later, a repeated colonoscopy confirmed that the lesions including longitudinal ulcers had disappeared. In this report, we describe our experience of this rare case of Behçet’s disease concomitant with colonic longitudinal ulcers and epithelioid granuloma, and discuss the difficulties in making a differential diagnosis, primarily with regard to Crohn’s disease.
Different outcomes of vertical transmission of hepatitis C virus in a twin pregnancy
Authors: INUI AYANO , FUJISAWA TOMOO , SOGO TSUYOSHI , KOMATSU HARUKI , ISOZAKI ATSUSHI , SEKINE ISAO
Published: March 2003

The risk of vertical transmission of hepatitis C virus (HCV) from mother to infant has been well documented, but the exact mode of transmission is still unclear. In a set of monochorionic diamniotic monozygous twins, only the second baby was infected with HCV from the mother who was positive for serum HCV‐RNA. The babies had an uncomplicated vaginal delivery 3 min apart and they were both bottle fed from the outset. The second baby developed clinical hepatitis that persisted to 30 months follow up. The intrauterine environment should have been identical for these twins, and therefore, the maternal HCV factors, including viral load are not the sole determining factors for mother‐to‐infant transmission of HCV.

© 2002 Blackwell Publishing Asia Pty Ltd
The additive effect of opioids and nitric oxide in increasing pentylenetetrazole‐induced seizure threshold in cholestatic mice
Authors: HOMAYOUN HOUMAN , SAYYAH MOHAMMAD , DEHPOUR AHMAD REZA
Published: March 2003

Background: Accumulation of endogenous opioids and overproduction of nitric oxide has been reported in cholestatic mice. It is well known that endogenous opioids and nitric oxide alter the susceptibility of experimental animals to different models of seizure.

Methods: The alterations in clonic seizure thresholds, induced by pentylenetetrazole from 1 to 6 days after bile duct ligation, were evaluated in mice. Whether the pretreatment of cholestatic mice with different doses of opioid receptor antagonist naltrexone, or nitric oxide inhibitor Nω‐nitro‐L‐arginine methyl ester would have changed the clonic seizure threshold was also examined.

Results: While in sham‐operated mice the clonic seizure threshold was similar to that of the thresholds in unoperated controls, a time‐dependent increase in the threshold was observed in cholestatic mice, reaching a peak on day 3 after bile duct ligation and declining partially after the 4th day. Chronic pretreatment with naltrexone (2, 5 and 10 mg/kg, i.p.) reversed the increased threshold in cholestatic mice on day 3 after operation in a dose‐dependent manner with the highest doses used restoring the threshold to that of the control animals. A similar reversal of the increased threshold was observed after acute (1, 3 and 10 mg/kg, i.p.) or chronic (10 mg/kg, i.p. for 4 days) pretreatment with Nω‐nitro‐L‐arginine

methyl ester. Moreover, concurrent administration of doses of Nω‐nitro‐L‐arginine methyl ester and naltrexone that each separately induced a partial reversal of increased seizure threshold in cholestasis caused a complete restoring of the threshold to the control level.

Conclusions: Based on these findings, both opioid receptors and nitric oxide may be involved in the dramatic increase in pentylenetetrazole‐induced seizure threshold in cholestasis.
Tumor necrosis factor‐α and transforming growth factor‐β reflect severity of liver damage in primary biliary cirrhosis
Authors: NEUMAN MANUELA , ANGULO PAUL , MALKIEWICZ IZABELLA , JORGENSEN ROBERTA , SHEAR NEIL , DICKSON E ROLLAND , HABER JULIA , KATZ GADY , LINDOR KEITH
Published: March 2003

Background and Aims The pathogenesis of primary biliary cirrhosis (PBC) is unknown. The role of cytokines such as tumor necrosis factor‐α (TNF‐α) and transforming growth factor‐β (ΤGF‐β), and the effect of ursodeoxycholic acid (UDCA) in modifying the cytokine environment in patients with PBC has remained largely unstudied. Our aims were to determine: (i) the relationship between serum levels of TNF‐α and TGF‐β and the severity of PBC; and (ii) the effects of UDCA therapy on TNF‐α and TGF‐β levels in patients with PBC.

Methods We studied 90 patients who had been treated with UDCA (53 patients) or placebo (37 patients) for 2 years as part of a randomized, double‐blind, controlled trial. Patients were divided into histological stage I/II or stage III/IV disease. Serum TNF‐α and TGF‐β levels were quantified by enzyme‐linked immunoabsorbent assay.

Results Baseline levels of TNF‐α were significantly greater in patients with stage III/IV compared to stage I/II disease. After 2 years of treatment with UDCA, patients showed a significantly greater decrease in TNF‐α levels and progression risk score compared to placebo‐treated patients. TNF‐α and TGF‐β levels were significantly reduced compared to baseline levels in the UDCA‐treated group after 2 years, while there was no significant change in the levels of placebo‐treated patients.

Conclusions Serum TNF‐α and TGF‐β levels may reflect severity of disease in patients with PBC. The beneficial effects of UDCA therapy may be explained by lowering serum levels of these two cytokines.
Genetic testing for HFE hemochromatosis in Australia: The value of testing relatives of simple heterozygotes
Authors: CAVANAUGH JULEEN A , WILSON SUSAN R , BASSETT MARK L
Published: March 2003

Abstract
Background
: It is unclear whether screening of relatives of C282Y and H63D heterozygotes (other than compound heterozygotes) for hemochromatosis will detect sufficient numbers of cases to justify introduction of this screening strategy.

Methods
: Conditional probabilities were determined using published Australian allele frequencies and penetrance data to determine the detection rate of hemochromatosis by testing the siblings and offspring of heterozygotes (subjects with only one HFE mutation).

Results
: The number of individuals who are at risk of developing increased body iron stores because of HFE mutations is substantially higher (1 in 80) than previously estimated. In addition, 33% of the Australian population are heterozygous for either C282Y or H63D. Based on population estimates, the relative risk to the offspring of C282Y and H63D heterozygotes of developing increased iron stores is 4.1 and 1.5, respectively, while the relative risk to each sibling is 2.3 and 1, respectively. The risk of developing clinical features of hemochromatosis or hepatic fibrosis is likely to be substantially lower.

Conclusions
: Although the detection rate from testing the families of unaffected heterozygotes is low, this can be justified as a clinically useful screening strategy. At the present time this strategy should be restricted to first‐degree relatives of heterozygotes. Further studies are recommended to determine if cascade genetic screening is a cost‐effective alternative to general population screening.

© 2002 Blackwell Publishing Asia Pty Ltd
Endoscopic hemostasis of a bleeding marginal ulcer: Hemoclipping or dual therapy with epinephrine injection and heater probe thermocoagulation
Authors: Lee Yi‐Chia , Wang Hsiu‐Po , Yang Chang‐Shiu , Yang Tzeng‐Huey , Chen Jiann‐Hwa , Lin Chun‐Che , Tsai Chiang‐Yen , Chang Li‐Ying , Huang Shih‐Pei , Wu Ming‐Shiang , Lin Jaw‐Town
Published: March 2003

Background and Aims:
Endoscopic hemoclipping and dual therapy with epinephrine injection and heater probe thermocoagulation have been proven effective in the hemostasis of bleeding peptic ulcers. However, the hemostatic efficacy has not been investigated in bleeding marginal ulcers. The aim of this study is to investigate the hemostatic efficacy of endoscopic hemoclipping and dual therapy with epinephrine injection and heater probe thermocoagulation in bleeding marginal ulcers.

Methods:
From November 1997 to July 2000, 50 patients with active marginal ulcer bleeding underwent either hemoclipping (20 patients) or dual therapy (30 patients) for hemostasis. The demographic data, clinicopathological characteristics, endoscopic findings, initial hemostatic rates, rebleeding rates, amount of blood transfusion, the need of surgery, and mortality rates were collected and analyzed.

Results:
Marginal ulcers were located at the anastomotic site (64%), saddle portion (22%), efferent loop (10%), or at the afferent loop (4%). The bleeding stigmata were classified into spurting artery (32%), oozing vessel (38%), visible vessel (20%), and blood clot adhesion (10%). The overall therapeutic results in 50 patients were initial hemostasis (100%), rebleeding rate (22%), need for surgery (4%), and hospital mortality rate (4%). There was no significant difference in demographic data and clinicopathological characteristics between the two modes of treatments, whereas recurrent bleeding developed in 5% in the hemoclipping group and 33% in the dual therapy group. No complication related to the procedure occurred in either mode of therapy. The hospital mortality rates were 0 and 6.7%, respectively.

Conclusion:
Endoscopy is effective in achieving initial hemostasis from bleeding marginal ulcers. However, the rebleeding rate remains high and repeated endoscopy may be needed to arrest the hemorrhage.

© 2002 Blackwell Publishing Asia Pty Ltd
Hepatitis flares and hepatitis B e antigen seroconversion: Implication in anti‐hepatitis B virus therapy1
Authors: LIAW YUN‐FAN
Published: March 2003

Abstract  Hepatitis flares or acute exacerbations, defined as an abrupt elevation of serum alanine aminotransferase (ALT) over fivefold the upper limit of normal (ULN), of chronic hepatitis B virus (HBV) infection are the results of HLA‐I restricted, cytotoxic T lymphocyte (CTL)‐mediated immune response against HBV and its downstream mechanisms. Higher ALT levels reflect a more vigorous immune response and a more extensive hepatolysis that, in the extreme situation, may lead to decompensation and failure. In contrast, higher ALT also reflects a more robust immune clearance of HBV and, therefore, a higher chance of HBV‐DNA loss and hepatitis B e antigen (HBeAg) seroconversion, both in the setting of natural course and drug therapy. Alanine aminotransferase of fivefold the ULN appears to be a significant cut‐off level to categorize the patients in terms of endogenous immune response against HBV. Patients with ALT levels less than fivefold the ULN or those with a less vigorous immune response require immunomodulation to induce robust immune response to enhance HBV clearance. In contrast, those with a more vigorous immune response or those with ALT flare over fivefold the ULN should be monitored closely for spontaneous HBV clearance/HBeAg seroconversion or to start direct antiviral therapy in time to prevent the occurrence or deterioration of hepatic decompensation. In conclusion, a better understanding of the pathogenetic mechanisms and natural course of hepatitis flares, wiser selection of patients and the timing of drug therapy are crucial to achieve better treatment results.
Cholangiocarcinoma in liver cirrhosis
Authors: HUI CHEE‐KIN , YUEN MAN‐FUNG , TSO WAI‐KUEN , NG IRENE OI‐LIN , CHAN ANNIE ON‐ON , LAI CHING‐LUNG
Published: March 2003

Background and Aim: Hepatocellular carcinoma (HCC) is usually associated with chronic liver diseases and liver cirrhosis, while conversely, cholangiocarcinoma (CC) usually occurs in a non‐cirrhotic liver. The purpose of the present study was to evaluate CC in liver cirrhosis.

Methods: Between January 1998 and December 1999, 26 patients with CC were retrospectively reviewed. The occurrence of CC in chronic hepatitis B infection‐related liver cirrhosis, portal vein thrombosis (PVT) and survival were analyzed.

Results: Twenty‐six patients with CC (19 with a non‐cirrhotic liver and seven with chronic hepatitis B infection‐related liver cirrhosis) were included in the present study. All cases of CC in the cirrhotic group were incidentally discovered during routine screening for HCC. The mean age (± SD) was 58.8 ± 14 years in the cirrhotic group and 73.2 ± 15.9 years (P = 0.001) in the non‐cirrhotic group. When compared to the cirrhotic group, the non‐cirrhotic group had a higher median level of albumin (42 compared to 30 g/L, P = 0.005), bilirubin (117.5 compared to 18 µmol/L, P = 0.01), alkaline phosphatase (291.5 compared to 100 U/L, P = 0.001) and gamma glutamyl transpeptidases (215.5 compared to 31 U/L, P = 0.001). In contrast, the cirrhotic group had a higher median prothrombin time (PT) compared to the non‐cirrhotic group (18.2 compared to 12 s, P = 0.05). In the non‐cirrhotic group, only one patient (5.3%) showed evidence of PVT on a computerized tomography and Doppler ultrasound, while in the cirrhotic group six patients (85.7%) had PVT (P < 0.001). The median survival period in the cirrhotic group was six months (range 2–24 months) compared to 16 months (range 6–41 months) in the non‐cirrhotic group (P = 0.036).

Conclusion: CC in cirrhotic liver presented at a younger age and patients who developed CC were prone to PVT. The survival period was also shorter in comparison to that of non‐cirrhotic liver patients.
Paediatricians: Referral rates and speech pathology waiting lists
Authors: KEATING D , SYRMIS M , HAMILTON L , McMAHON S
Published: March 2003

Objective:

This study aimed to examine paediatricians’ training in and understanding of communication development and disabilities and their attitudes to speech pathology waiting lists and management practices. The relationship between these factors and referral rates was also investigated.

Methodology:

A total of 229 paediatricians registered with the Australian College of Paediatrics participated in the study in November 1996. They answered 15 multiple‐choice questions designed to collect demographic information and data pertaining to their training and understanding of communication development and disabilities. The survey also obtained data on referral rates to public and private speech pathology services and on paediatricians’ perceptions of speech pathology waiting lists and possible management strategies.

Results:

Referral rate to public and private speech pathology services was found to be associated with the quality of paediatricians’ training in and knowledge of communication development and disabilities. Paediatricians who had regular contact with speech pathologists were also more likely to make more referrals. Waiting lists had a negative influence on referral rate. Treatment rather than assessment waiting lists were preferred. Paediatricians believed the best solution to speech pathology waiting lists was an increase in staffing levels particularly in community health centres. Respondents reported that 1–4 months was an acceptable time to wait for speech pathology care and indicated the order of importance of factors for prioritising children.

Conclusions:

The results have important implications for developing best practice models for improving referral processes and access to speech pathology services for children with communication disabilities.
Gentamicin dosage intervals in neonates: Longer dosage interval—less toxicity
Authors: DAVIES MW , CARTWRIGHT DW
Published: March 2003

Objectives:

The aim of this study was to determine the incidence of toxic trough serum gentamicin levels in neonates in the first week of life, with different dosage intervals.

Methods:

This was a retrospective study of neonates born between 01.07.95 and 31.12.95, who received gentamicin. Data were collected on birth weight, gestation, gentamicin dose, the trough level of gentamicin, serum creatinine and urine output. A trough serum gentamicin level of ≥1.5 mg/L was considered toxic.

Results:

One hundred and seventy infants met the study criteria. All 21 infants in group one (24–29 weeks) received gentamicin with a dosage interval of 24 h. Sixteen (76%) infants had toxic trough serum gentamicin levels. In group two (30–34 weeks) 8 infants had gentamicin q12hly and all (100%) had toxic trough serum gentamicin levels. Fourteen infants had gentamicin every 18 h and 13 (93%) had toxic trough serum gentamicin levels. Sixty‐one infants had gentamicin q24hly and 25 (41%) had toxic trough serum gentamicin levels. The differences in proportions with toxic levels were statistically significant. In group three (≥35 weeks) 29 infants had gentamicin q12hly and 25 (86%) had toxic trough serum gentamicin levels. Six infants had gentamicin every 18 h and 2 (33%) had toxic trough serum gentamicin levels. Thirty‐one infants had gentamicin q24hly and 4 (13%) had toxic trough serum gentamicin levels. The differences in proportions comparing infants having gentamicin q12hly with those having it q24hly were statistically significant.

Conclusions:

A starting gentamicin dosage interval of 12 h in infants of any gestational age, or a starting dosage interval of 24 h for infants of less than 30 weeks gestational age, leads to most having toxic trough serum gentamicin levels. In infants of 30 weeks gestational age or greater, most have safe non‐toxic trough serum gentamicin levels if started on a dosage interval of 24 h.
Low dose oral anticoagulation therapy in Chinese children with congenital heart disease
Authors: CHEUNG YF , LEUNG MP
Published: March 2003

Objectives:

This study aims to evaluate the efficacy of a low dose warfarin regimen for Chinese children requiring anticoagulation therapy and its safety when monitored on an outpatient basis. Current recommendations are based on extrapolations from the adult experience and a high target international normalised ratio (INR) is adopted amongst the Western countries.

Methodology:

This is a 10‐year retrospective study from January 1986 to June 1996. Effectiveness of warfarin therapy was monitored by the prothrombin time, standardised and expressed as the INR. A target INR of 1.5–2.5 was adopted for children with cardiac diseases requiring anticoagulation therapy for primary and secondary prophylaxis against thromboembolism. From the clinical records, demographic data, induction warfarin dosage, changes of dosages and related events on follow‐up, frequency of outpatient visits, complications and serial INR results were reviewed.

Results:

Thirty‐five patients (23 boys, 12 girls) were included with a mean age at initiation of warfarin therapy of 8.4±5.8 years. Amongst these, 66% (n=23) were after isolated valvar replacement, 28% (n=10) after Fontan operation with or without valvar replacement and 6% (n=2) after deep vein thrombosis. Regression estimate of the induction dose was 0.05–0.13 mg kg−1 in order to achieve the target INR range after 2 days of warfarin therapy. The daily maintenance warfarin dose was correlated with the bodyweight [dose (mg day−1)=0.04×bodyweight (kg)+0.87, r=0.63, P<0.0001]. Young children required significantly higher daily warfarin maintenance dose when adjusted for bodyweight [dose (mg kg day−1)=antilog10{−0.02×age (years)−0.80}, r=−0.74, P<0.0001]. The mean maintenance warfarin dosage was significantly lower in patients after the Fontan operation, with or without valvar replacement, in the absence of apparent liver dysfunction. The total period of follow‐up was 159 patient‐years. No serious bleeding complications or embolic phenomena were documented. One patient died of thrombosis of the mitral valve prosthesis. The overall incidence of thrombosis was 0.6 per 100 patient‐years.

Conclusions:

A low dose warfarin regimen to maintain a target INR of 1.5–2.5 provides adequate protection in Chinese children against thromboembolism whilst allowing safe outpatient monitoring of the anticoagulation status.
Incidence of invasive pneumococcal disease in Sydney children, 1991–96
Authors: Liddle JLM , Mcintyre PB , Davis CWC
Published: March 2003

Objective: Few data are available on invasive disease due to Streptococcus pneumoniae in representative Australian childhood populations. This study aimed to determine the age‐specific incidence of invasive pneumococcal disease in Sydney children.

Methodology: Population‐based prospective study where isolates of Streptococcus pneumoniae from normally sterile sites were identified through an established laboratory surveillance network. Isolates came from children aged under 15 years living within the boundaries of Central, Eastern, Southern, Western and South‐western Sydney Area Health Services from 1 July 1991 to 30 June 1996.

Results: Invasive pneumococcal disease was identified in 320 children during a 5‐year period, of whom 193 (60%) were under 2 years of age. The incidence per 100 000 children was 12.7 per 100 000 (95% CI: 11.4–14.2/100 000) under 15 years; 31.7 (95% CI 28.1–35.7) under 5 years, and 45.5 (95% CI 38.9–53.3) under 2 years. The incidence of pneumococcal meningitis in children aged under 2 years was 10.5 per 100 000 (95% CI: 7.4–14.5/100 000).

Conclusions: The incidence of childhood invasive pneumococcal disease in Sydney was stable during 1991–96 and comparable to rates reported from other industrialized countries. There was no evidence of any change in pneumococcal disease incidence with reduction in invasive Haemophilus influenzae type b (Hib) disease following introduction of Hib immunization.