Search

A basin-hopping search strategy has been used to determine likely candidates for low-energy Rh(n)S(0,±) (n = 1-9) cluster structures. Cluster structures were optimized at the density functional level of theory using the PBE and PBE0 functionals. Ionization energies, electron detachment energies, HOMO-LUMO gap energies, UV-visible spectra, low-lying fragmentation channels and energies, cluster structures, spin multiplicities, and vibrational spectra are predicted for Rh(n)S(0,±) and Rh(n+1)(0,±) (n = 1-9). Donation from valence sulfur atomic p orbitals to valence rhodium atomic d orbitals and back-donation to valence sulfur atomic d orbitals leads to electron density delocalization and metal-like behavior for rhodium sulfide clusters.

The Ministry of Health (MOH) publishes clinical practice guidelines on Chronic Hepatitis B Infection to provide doctors and patients in Singapore with evidence-based guidance on managing important medical conditions. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH clinical practice guidelines on Chronic Hepatitis B Infection, for the information of readers of the Singapore Medical Journal. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website (http://www.moh.gov.sg/mohcorp/publications.aspx?id=26108). The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

A novel compound, (5-(dimethylamino)-N-(4-ethynylphenyl)-1-naphthalenesulfonamide), was prepared and characterized; it shows dual functional roles as an effective antitumor and a two-photon induced bio-imaging agent.

Introduction: Minimal hepatic encephalopathy (mHE) has been reported in up to 84 percent of cirrhotics. The natural history of mHE has not been well-described. We designed a three-year prospective cohort study to determine the prevalence and natural history of mHE among cirrhotic patients., Methods: The patient cohort comprising 62 consecutive outpatients with cirrhosis were assessed at baseline and followed-up with a repeat assessment three years later. The assessments include: (1) Neuropsychometric analysis (digit-symbol substitution test, block-design test, number-connection test A); (2) Clinical, biochemical assessment; and (3) Quality of life (QOL) assessment (abbreviated sickness impact profile)., Results: Baseline characteristics were: age 52.9 +/- 11.0 years; Child's A:B:C was 46:14:2. mHE was detected in 33.9 percent of the cohort. Older age, a higher Child-Pugh score and female gender were independently associated with mHE. mHE was associated with a poorer QOL. Follow-up assessment three years later showed that seven patients had died, while six were lost to follow-up; these patients had significantly higher baseline Child's scores. Of the remaining patients, 36/49 (73 percent) agreed to a repeat evaluation. In this group, none had mHE. QOL remained impaired despite the resolution of mHE., Conclusion: It has been shown for the first time that mHE can revert to a normal state in a significant proportion of patients with well-compensated cirrhosis.

Background: Transient elastography (TE) is a reliable non-invasive predictor of hepatic fibrosis, but data on TE in Asians are limited., Aim: To evaluate prospectively the accuracy of TE for diagnosis of hepatic fibrosis in Asians compared with APRI (aspartate transaminase to platelet ratio index)., Methods: One hundred and twenty consecutive patients who underwent liver biopsy were enrolled. TE (Fibroscan) was performed by two independent operators. Fibrosis was graded by two independent pathologists using the METAVIR classification. Area under receiver operating curves (AUROC) were used to evaluate the accuracy of TE and APRI in diagnosing significant fibrosis (F >or= 2) and cirrhosis (F4)., Results: Predominant aetiologies were hepatitis B (48%), non-alcoholic steatohepatitis (14%) and hepatitis C (8%). TE was unsuccessful in five patients (4.2%) because of small inter-costal space (three patients), obesity and ascites. There was good correlation between TE and fibrosis (r = 0.606). AUROC for diagnosis of significant fibrosis was 0.856 (95% CI 0.779-0.932) for TE and 0.673 (95% CI 0.568-0.777) for APRI. AUROC for diagnosis of cirrhosis was 0.924 (95% CI 0.857-0.990) for TE and 0.626 (95% CI 0.437-0.815) for APRI. Optimal TE value was 9.0 kPa for diagnosis of significant fibrosis and 16.0 kPa for cirrhosis with specificity/sensitivity/PPV/NPV/accuracy of 82.6%/85.2%/80.9%/86.7%/84.1% and 88.9%/82.7%/32.0%/98.8%/83.2%, respectively., Conclusions: Transient elastography is a reliable predictor of hepatic fibrosis in Asians. Failure of TE in Asians is commonly because of small inter-costal space. TE is superior to APRI for non-invasive diagnosis of hepatic fibrosis and cirrhosis.

Imatinib mesylate (Gleevec) is widely-used in the treatment of chronic myeloid leukaemia (CML) and gastrointestinal stromal tumour. Up to four percent of patients treated with imatinib may develop hepatotoxicity, which usually resolves with discontinuation of the drug. We report a 45-year-old Chinese man with CML and chronic hepatitis B virus infection, on imatinib treatment, presenting with herpetic rash and acute liver failure. This case illustrates the diagnostic challenges in the management of such a patient, as well as the need for greater vigilance in the monitoring of liver function tests for patients treated with imatinib. A short review on imatinib-related hepatotoxicity is also presented.

This retrospective study evaluated patients admitted to the Department of Gastroenterology, Singapore General Hospital for variceal bleeding in the year 2004. Improvement in outcome of variceal bleeding has been reported in the West. There is no regional data on this condition. This study aims to determine the characteristics and outcome of variceal bleeding in a tertiary hospital in Southeast Asia. Twenty-two patients were eligible. The main aetiologies of liver cirrhosis were chronic hepatitis B (38%) and alcohol (33%). Child's A, B and C were 29%, 48% and 24% respectively. Nineteen patients (86%) had bleeding oesophageal varices (band ligation performed). The remaining three patients (14%) had bleeding gastric varices (N-butyl-2-cyanoacrylate injection performed). Detailed description of certain endoscopic findings was absent in up to 18 patients (82%). All patients received antibiotics and vasoactive drug. In-hospital mortality and rebleeding were 9% and 18% respectively. We conclude that the relatively low in-hospital mortality and rebleeding rates in our series are most probably due to the smaller proportion of patients with severe liver dysfunction and management which adhered to recommendations. Documentation of endoscopic findings needs to be improved to facilitate the continuation of care.

Introduction: To characterise the anthropometrical and metabolic parameters of a group of non-diabetic and non-obese patients who had histologically-proven nonalcoholic steatohepatitis (NASH)., Methods: During September 1997 to November 1999, consent for liver biopsies were sought from a consecutive series of patients, whose body mass index (BMI) were equal to or less than 30 kg per square metres, and who had persistently elevated serum alanine transaminase (more than 2.5 times upper limit of normal for more than six months), with no associated viral hepatitis, alcohol or drug-induced liver disease, hereditary liver disease and diabetes mellitus. Patients who were found to have steatohepatitis histologically were further studied. Their body weight, height, waist and hip circumferences were taken, and fasting serum lipid and glucose measured. Serum insulin was measured in six patients and insulin resistance (IR) was calculated by homeostasis model assessment. Oral glucose tolerance tests were done if fasting glucose levels were greater than 6 mmol/L. All liver biopsies were reviewed by a single histopathologist. Three age- and sex-matched controls were randomly selected for each patient., Results: 11 of 12 patients who underwent liver biopsies were found to have NASH. All 11 were Chinese: eight males and three females. 73 percent of them had hepatic fibrosis. Overall, compared to controls, they had significantly higher body weight, BMI, IR and triglyceridaemia. The female patients also had a higher waist-hip ratio than controls. None had diabetes mellitus, and one had impaired glucose tolerance/fasting glycaemia. Nine out of 11 had BMI between 25 and 30 kg per square metres., Conclusion: Significant histological changes of NASH with hepatic fibrosis were found in Singaporean Chinese non-diabetic patients with BMI of less than 30 kg per square metres.

Non-steroidal anti-inflammatory drugs (NSAIDs) and cyclo-oxygenase-2 (cox-2) inhibitors are structurally heterogeneous drugs that share similar therapeutic actions and adverse effects. Hepatotoxicity, although a relatively rare adverse effect of this class of drugs, can be severe. This has led to the withdrawal of some NSAIDs from the market. Nimesulide is an NSAID, with cox-2 preference, which has been reported to cause death from hepatic failure. However, most reports have been from European countries. Asian reports include that from Israel and India. We report three patients who presented with acute hepatitis after being prescribed nimesulide, one of whom died from fulminant hepatic failure.

The prevalence of hepatitis G virus (HGV) infection in patients with liver diseases in Singapore and its pathogenic role in these patients was studied. One hundred and forty-eight patients who had chronic hepatitis or acute non A-E hepatitis were studied. Presence of HGV RNA was determined by nested polymerase chain reaction of the 5'non-coding region of the virus in all the patients. Hepatitis G IgG antibody to the envelope (E2) antigen was tested with an enzyme immunoassay (Boehringer Mannheim, Singapore) in 76 of them. Most patients (93%) were ethnically Chinese, predominantly males (74%) and chronic hepatitis B (72%) patients. Others had chronic hepatitis C (19%) or cryptogenic cirrhosis (6%). Four patients had acute non A-E hepatitis. HGV RNA and anti-HGenv were present in 3.5% and 8.3% of those with chronic liver disease. HGV infection did not account for any of the acute non A-E hepatitis and most of the cryptogenic cirrhosis.

This paper addresses two difficult issues in the treatment of hepatitis C: patients who fail to achieve a sustained response after the first course of treatment, and those who simultaneously suffer from chronic renal failure. With the recent improvements in firstline treatment, retreatment is mainly applicable to those who have previously received 6-month of interferon monotherapy at 3 MU thrice weekly. For those who had an end-of-treatment response but relapsed, there is a choice between interferon monotherapy at increased dose and/or duration of treatment, or a 6-month course of combination therapy. Retreatment of non-responders is generally unsuccessful, but some patients may respond to interferon-alpha 3 MU and ribavirin 1.0-1.2 g/day. For patients with chronic renal failure and hepatitis C, combination treatment is not possible because ribavirin is contraindicated. Interferon given at a dose of 1.5 MU thrice weekly was reported to be fairly well tolerated by patients who were on dialysis and resulted in end-of-treatment and sustained biochemical and virological response in some cases. Interferon given in the usual doses may be associated with severe adverse effects in patients with renal failure, and can precipitate allograft rejection in patients who have undergone renal transplantation.

Granulocytic sarcoma (GS) is an increasingly common relapse feature of acute myeloid leukemia (AML), late in the disease course or post bone marrow transplantation (BMT). Any solid organ can be affected, and there have been a number of reports of GS in breast tissue in female patients. We present a unique case of GS in a male AML patient, presenting as painless gynecomastia immediately before BMT at advanced disease. Aberrant expression of CD56 was found in the relapsed GS tissue but not in the original AML clone. Twelve months after allogeneic BMT, leukemia relapsed again in the same breast, with normal marrow morphology and full donor chimerism. The lesion failed to respond to donor lymphocyte infusion, chemotherapy and radiotherapy, and disseminated to other subcutaneous tissues.

To assess whether demography is one of the important factors determining antibody response to nuclear antigens [ANA: SSA-Ro (52K and 60K), SSB-La, snRNPs (A, 70K, B'/B), and Cenp-B], we investigated 95 and 47 sera of autoimmune hepatitis (AIH) from North America and Asia, respectively, by immunofluorescent (IF) and recombinant ELISA. Correlations among nuclear IF patterns, ELISA, and disease indices were analyzed. The frequency and titer of individual antibodies differed significantly between the groups. Patients with speckled patterns were younger in both regions and had higher aspartate aminotransferase levels only in North America. HLA-A1, B8, DQ2, and DR4 or DR3 or both in North America, and A2, B61, DQ7, and DR4 in Asia were predominant. In Asia, B61 correlated with anti-70K, and DQ7 correlated with antibodies to 52K, Cenp-B, and B'/B. In North America, A1, B8, DR3 haplotype, and DQ2 correlated with antibodies to A and 70K. Anti-B'/B and DR4 in North America, and A2 in Asia, were associated with concurrent immunologic disorder. Individual ANA clusters correlated with individual HLA in the demography, and different HLA alleles might determine disease expression as well as different ANA being produced in AIH.

Treatment of patients with chronic hepatitis C has had limited success because of relapses and nonresponse to interferon alfa therapy (currently the only established therapeutic agent). A retrospective study was done to determine the efficacy of re-treatment with interferon and the predictors of response in patients who failed to achieve sustained response after one standard course of interferon therapy (3 million units three times a week for 24 weeks). One hundred and eleven patients (47 relapsers and 64 nonresponders), mean age 45 years, were included in the study. Eighteen relapsers and 13 nonresponders received a higher dose (5 MU), and 11 relapsers and 6 nonresponders received a longer duration (48 weeks) of interferon therapy. The remaining patients received the same regimen as the first treatment. Eighty-one percent and 23% of relapsers and nonresponders, respectively, had an end-of-treatment response, and 19% and 3% of the corresponding patient groups had a sustained response to re-treatment. Two patients with breakthrough during their first treatment were the only nonresponders with sustained response after re-treatment. Sustained response was observed only in patients who received an increased dose or duration of interferon therapy. No predictor of sustained response was found. In conclusion, sustained response to re-treatment with interferon was only observed with augmentation of dose or duration of therapy in some relapsers and patients who had breakthrough. Established predictors of response to interferon in naive patients, in particular serum hepatitis C virus RNA and genotype, were not associated with sustained response to re-treatment.

The development of molecular biology techniques has enabled us to clone the genetic sequence of three new hepatitis viruses, namely, hepatitis C virus, hepatitis E virus and hepatitis G, or GBV-C virus in the last decade. Hepatitis C virus (HCV) is now known to account for the majority of the parenterally transmitted non-A, non-B hepatitis and hepatitis E virus (HEV) is the major cause of the epidemics of enterally transmitted non-A, non-B hepatitis in the less developed countries, mainly through contaminated water supplies. While 80% of those who were infected with HCV will become chronic carriers, there is no known chronic carrier state for HEV. To date, 6 major genotypes of HCV were identified, with various variants of genotype 6 described in Southeast Asia. In Singapore, the majority of our chronic hepatitis C patients are infected with genotype 1. The seroprevalence rate of HEV is 10% to 14% in Singapore. This probably reflects our suboptimal sanitary condition in the past rather than a reflection of a currently high HEV infection rate in our population. However, local cases of acute hepatitis E have been reported. As for the most recently cloned hepatitis G virus, its aetiologic role in the remaining cases of non-A, non-B hepatitis is still unclear. Some preliminary evidence suggests that it may be just an innocent bystander with limited pathogenicity and it certainly cannot account for all the remaining cases of non A-E hepatitis. Hence, the search for yet another hepatitis virus continues.

Seroprevalence of hepatitis E is now documented in many countries around the world, but studies of its clinical manifestations and serologic course have been confined to endemic areas. We have prospectively evaluated the occurrence, evolution, and outcome of acute hepatitis E in our patients. Fifteen patients (11 men, 4 women; median age: 41 years) were diagnosed to have acute, sporadic hepatitis E between July 1993 and January 1995; 10 of the 15 were followed up. Sera anti-hepatitis E virus (HEV) immunoglobulin (Ig)G and IgM antibodies and HEV ribonucleic acid in the blood and stool were tested at weeks 1 and 2; serial tests for hepatitis E antibodies and liver function were carried out at months 1, 3, 6, 9, 12, and 18. Coinfection with hepatitis A and superinfection on chronic hepatitis B were found in 3 and 2 patients, respectively. One patient had transient passage of virus in the stool, but none was viremic. Eighty-seven percent of patients lost their IgM antibodies within 3 months, but anti-HEV IgG, once present, persisted throughout follow-up. All patients but one had complete recovery. A higher than reported level of alanine transaminase (mean: 28.5 times normal) and the lack of viremia during acute infection in our patients may be due to increased immune-mediated viral clearance.

The seroprevalence of anti-HEV IgG was determined in a hospital-based population in a general medical unit. Patients who were otherwise well but admitted for acute, non-hepatological conditions represent the "healthy" general population, and those admitted primarily with liver disorders were studied. The seroprevalence of anti-HEV IgG was found to be 10.5% in the "healthy" population and 14.7% amongst those with liver diseases. The lack of travel history and past history of jaundice suggests presence of local cases and subclinical manifestation in some of the infected patients. There is an association between seroprevalence of hepatitis A and E, suggesting common predisposing factors for both infections. Anti-HAV IgG has a higher seroprevalence. Retesting of anti-HEV IgG in those who were initially positive found persistence of antibodies beyond twelve months. Both anti-HAV IgG and anti-HEV IgG were found more commonly in the older age groups.

Malignant histiocytosis, as defined by Rappaport, is now known as a manifestation of malignant lymphoma, the majority of which is the T-cell type. However, unlike the typical presentation of most non-Hodgkin lymphomas, this condition presents with atypical features mimicking acute hepatitis or infectious mononucleosis. The latter diagnosis is often made because of the occurrence of atypical mononuclear cells on the peripheral blood films. This is clearly seen in the seven patients we report where the initial diagnoses were that of viral fever or hepatitis. Some characteristics were found in these patients to differentiate the condition from infectious mononucleosis (IMS) and acute hepatitis (AH): paucity of lymph nodes, cholestasis and prolonged prothrombin time (PT) which is atypical IMS; persistent fever, thrombocytopaenia and disproportionately high aspartate aminotransferase which is unusual in AH in the absence of any drug or alcohol history. The PT is the most important prognosis factor. Early diagnosis and treatment led to improved survival in an otherwise aggressive and rapidly fatal condition.

The present report describes a Chinese male who presented for the first time with recurrent encephalopathy and hyperammonaemia at the age of 52 years. He was found to have citrullinaemia. To our knowledge, this is the first Chinese with citrullinaemia and the first non-Japanese who has the variant form of presentation. The patient also has the longest asymptomatic period for citrullinaemia so far described. The patient's biochemical derangement, clinical features and the postulation of his late presentation are discussed. It is noteworthy that simple therapeutic measures, such as lactulose and dietary protein restriction, controlled his symptoms well.

The immunogenicity and reactogenicity of an inactivated hepatitis A virus (HAV) vaccine was studied in healthy Singaporean adult volunteers. One hundred and forty healthy volunteers with normal alanine (ALT) and aspartate (AST) transaminases and no previous exposure to HAV, received three 1 ml doses (720 ELISA units) of an inactivated HAV vaccine (Smithkline Beechams Biologicals) following a 0, 1, 6 months vaccination schedule. All subjects were asked to record and grade the severity of any reactions for three consecutive days after each dose. Serum ALT and AST as well as anti-HAV were measured at 0, 1, 2, 6 and 7 months after the first vaccine dose. Anti-HAV seroconversion occurred when levels rose above 40 mIU/ml. Eighty-five percent of vaccinees seroconverted after the first innoculation and 99% after the second injection. All vaccinees seroconverted after the third dose. Geometric mean anti-HAV titers (GMTs) were, respectively, 119, 391, 4406 mIU/ml one month after each of the three doses. The most common side effect was transient pain and tenderness at the vaccination site. No elevation of ALT or AST levels were noted during the study period. The inactivated hepatitis A vaccine used in this study is safe and highly immunogenic in the local adult population. Two doses one month apart appeared to give adequate protection.

Between 1992 and 1994 the Paediatric Metabolic Centre screened 403 patients for inherited metabolic disease. Seventeen patients were diagnosed, including 7 with organic acidurias, 5 with mucopolysaccharidoses, 2 with amino acid disorders, 2 with carbohydrate disorders and 1 with hyperlipidaemia. The ethnic distribution of disorders in Singapore is compared with incidences reported by others in this part of the world. It is likely that further studies will indicate which diagnostic or screening tests would best serve this community.

Over an 18-month period, 31 cholecystectomies were performed for empyema of the gall bladder. Analysis of these 31 cases showed that clinical features referable to the diagnosis and seriousness of this condition were few. The presence of a gall bladder mass was detected in only 35% of patients. In adopting a policy of early cholecystectomy for patients admitted for acute gall bladder disease, a low mortality rate of 3.2% was achieved for this group of patients with empyema of the gall bladder. Based on these results, we found that empyema of the gall bladder is another good reason to support early cholecystectomy.

Gallstone obstruction of the cystic duct with resulting repeated attacks of inflammation and pressure necrosis leads to the formation of cholecystocholedochal fistulas (Mirizzi syndrome type II). Obstructive jaundice and cholangitis are the common presentations of the condition. These fistulas are often not recognized before operation and constitute a high risk of damage to the common duct during a formal cholecystectomy. A high index of suspicion is required to diagnose the condition. We report five patients with cholecystocholedochal fistulas diagnosed by endoscopic retrograde cholangiography that delineated the fistula and the obstructing stone. The plan of management was formulated before surgery, and persistent attempt to dissect the Calot's triangle was avoided. In three patients the common duct defect was closed with the use of a gallbladder flap. Hepaticojejunostomy was required for the two difficult cases with large common duct defects and inflamed tissue.

A prospective study was carried out to evaluate the use of routine operative cholangiography in 382 patients undergoing elective cholecystectomy. Operative cholangiography was performed in 356 patients. In each patient, the presence or absence of clinical and operative indications for common duct exploration was correlated with the result of the operative cholangiography. In 114 patients (32%) there were one or more indications for exploration and only 34 patients showed positive cholangiographic findings and were explored. Ductal stones were found in 25 patients and nine patients had negative explorations. In the remaining 242 patients who had no indication for common duct exploration, normal cholangiogram was obtained in 234 patients and eight had false positive cholangiograms and were explored unnecessarily. No unsuspected common duct stones were detected in the whole series. Based on these results, a plea is made for selective operative cholangiography.

Microcystic adnexal carcinoma (MAC) is a recently described rare adnexal neoplasm showing benign histologic features but a locally aggressive behavior. It has most commonly been reported to occur on the face but it has also been noted in the axilla and buttock. We describe a 41-year-old white male with a 5-year history of MAC on the scalp and treatment by Mohs micrographic surgery. To our knowledge, this is the first case of MAC reported to occur on the scalp.