Biomedical subjects
Publications and source records attributed to C K Tan.
Spontaneous perforation of pyometra is an extremely rare emergent gynecologic disease. We report a 73-year-old woman with a spontaneously perforated pyometra presenting with acute abdomen in the emergency department. A dedicated computed tomography examination of the abdominal and pelvic regions revealed the diagnosis. The patient recovered well after surgical intervention and antibiotic treatment.
INTRODUCTION: Liver transplantation is the accepted standard of care for patients with hepatocellular carcinoma, decompensated liver cirrhosis, and acute liver failure. Since the first liver transplant done in Singapore in 1990, results have been improving. We review the overall results of liver transplantation over the last 15 years. METHODS: All transplant cases from 1990 to 2004 were reviewed retrospectively. RESULTS: 100 liver transplants were performed over the last 15 years; four in the first five years and 96 in the subsequent ten years. Overall one- and five-year survival rates were 80 percent and 78 percent, respectively. 44 were paediatric transplants, of which biliary atresia was the commonest indication for paediatric transplant. 56 were adult transplants of which hepatocellular carcinoma and decompensated hepatitis B cirrhosis were the commonest indications for adult transplant. Infection remained the commonest cause of mortality. CONCLUSION: The number of transplants carried out per year was small due to the low cadaveric donation rate, but the survival of liver transplant patients was comparable to well-established liver transplant centres.
INTRODUCTION: Referral patterns, waiting times, waiting list, and mortality provide information on how effectively a transplant programme deals with referred patients. This paper aims to review these parameters in the Singapore National Liver Transplant Programme. METHODS: Data of all patients referred to the Singapore National Liver Transplant Programme since its inception were captured and outcomes were retrieved and described. RESULTS: 562 patients were referred for liver transplant evaluation from 1990-2004, consisting of 457 adults and 105 children. The main indications for referral were hepatitis B liver disease and hepatocellular carcinoma in adults, and biliary atresia in children. Most patients were of United Network of Organ Sharing (UNOS) status 3 or 4 at the time of referral. 114 (20.28 percent) patients had transplants, consisting of 66 adults (14.44 percent) and 48 (45.71 percent) children. 138 adults and ten children were rejected for transplant, mainly for the reason of being "too early". The median waiting time for adults who had transplants was 3.3 months while adults still on the waiting list had been waiting for 16.2 months. The overall waiting list mortality was 44.3 percent, being 52.5 percent in adults and 23.2 percent in children. CONCLUSION: The overall transplantation rate is low and the waiting list mortality is high as a result of low availability of organs, particularly in adults. Paediatric liver transplant appears to have been better at dealing with referred patients but this is probably due to availability of living-related liver transplant. Improvement in these may result from the Human Organ Transplant Act.
OBJECTIVES: To examine the risk of high-flow type II endoleak following endovascular repair of abdominal aortic aneurysm with aortocaval fistula. DESIGN: Case reports. SUBJECTS: Two patients with abdominal aortic aneurysms with aortocaval fistula. METHODS: Both patients had an endovascular repair of their aortic aneurysms. RESULTS: The aneurysms were successfully treated in both patients, without any endoleak on completion angiography. Apart from a transient type II lumbar endoleak in one of the patients, no endoleak was found after 3 and 12 month follow-up. Seven other cases have been published, reporting one type II and one type Ic endoleak. CONCLUSION: We found no evidence that endovascular repair of abdominal aortic aneurysm with aortocaval fistula is associated with a higher incidence of persistent endoleak.
BACKGROUND/METHODS: Molecular Adsorbent Recirculating System (MARS) was used in three consecutive critically ill patients at the Singapore General Hospital with advanced malignancy and acute liver failure (ALF). Case 1 was a male patient with hepatocellular carcinoma (HCC) for which initial right hepatectomy was followed by left hepatectomy 5 months later for recurrent HCC. The postoperative course following second surgery was complicated by severe methicillin-resistant Staphylococcus aureus (MRSA) sepsis, mild azotaemia and subacute cholestatic liver failure. MARS was used thrice in this patient. Case 2 was a female patient with advanced acute lymphoblastic leukaemia (ALL) with post bone marrow transplantation (BMT) acute haemolytic-uraemic syndrome (HUS) secondary to cyclosporin A (Cy A), cytomegalovirus (CMV) infection, severe nosocomial pneumonia, acute renal failure (ARF) treated with continuous haemofiltration and acute veno-occlusive disease resulting in Budd-Chiari syndrome. The latter precipitated ALF. MARS was instituted twice. Case 3 was a male patient with advanced, refractory Hodgkin's disease previously treated with multiple courses of chemotherapy. ALF developed secondary to acute viral hepatitis B flare. He was given a trial of MARS once in the ICU. All the three patients eventually died. RESULTS: Mean MARS intradialytic systemic pressures were as follows: systolic pressure range was 95 +/- 17 to 128 +/- 17 mmHg and diastolic pressure range was 51 +/- 5 to 67 +/- 7 mmHg. Pressure at albumin dialysate exit point from dialyser 1 (Ae) ranged from 253 +/- 11 to 339 +/- 15 mmHg and that at albumin dialysate entry point into dialyser 1 (Aa) ranged from 142 +/- 11 to 210 +/- 6 mmHg. Ultrafiltration (UF) was 633 +/- 622 mL over mean treatment duration of 6.3 +/- 0.9 h with a total heparin dose of 1583 +/- 817 IU. Coagulation status pre- and 6-h post-MARS was similar: aPTT (P=0.116) and platelet count (P=0.753). There were no bleeding complications or circuit thromboses. MARS had a significant de-uraemization effect (pre- and post-MARS serum creatinine and urea: P=0.046 and 0.028, respectively) but did not significantly attenuate blood lactate, ammonia or total bilirubin levels. Albumin dialysate (Ae - Aa) urea and creatinine concentrations appeared to be sharply attenuated after 6 h of MARS. In contrast, the removal of total bilirubin by albumin dialysate from the blood compartment appeared to plateau after 4 h of continuous MARS operation. CONCLUSIONS: MARS was well-tolerated in critically ill patients with advanced and complicated cancer. Low-dose heparin was safe and did not compromise MARS circuit integrity. Although MARS had a significant de-uraemization effect, this appeared to be limited by the duration of MARS operation. Our data suggested that such a limit was reached earlier for total bilirubin. More data are needed to confirm the present findings and further delineate the saturation limit of MARS for different toxins that accumulate in ALF. This would affect the optimal duration of MARS therapy.
One day old rats received daily injections of dexamethasone and were sacrificed 24 h after the 1st and 7th injections. Neuronal death by apoptosis in the hippocampus was investigated by immunohistochemistry using bcl2, bax and caspase3 antibodies. The immunoreactivity expressed by the pyramidal neurons and the dentate granule cells with these antibodies was comparable in the dexamethasone treated and control rats injected with saline. At the ultrastructural level, the dendrites showed vacuolation indicative of degeneration in the dexamethasone administered rats. Results of reverse transcriptase-polymerase chain reaction analysis showed that bcl2 and bax mRNA was constitutively expressed in the hippocampus of control rats and showed no significant change in the dexamethasone treated rats. The results of this study indicate that dexamethasone induces degeneration of the dendrites but does not induce neuronal apoptosis in the hippocampus of postnatal rats.
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.
A cDNA encoding a protein of 36 kDa, polymerase delta-interacting protein 1 (PDIP1), that interacts with the small subunit (p50) of DNA polymerase delta (pol delta) was identified in a two-hybrid screen of a HepG2 cDNA library by using p50 as bait. The interaction of PDIP1 with p50 was confirmed by pull-down assays, and a similar assay was used to demonstrate that PDIP1 interacts directly with the proliferating cell nuclear antigen (PCNA). PCNA and p50 bound to PDIP1 simultaneously, and PDIP1 stimulated pol delta activity in vitro in the presence, but not the absence, of PCNA, suggesting that PDIP1 also interacts functionally with both p50 and PCNA. Subcellular localization studies demonstrated that PDIP1 is a nuclear protein that colocalizes with PCNA at replication foci. A putative PCNA-binding motif was identified within the C terminus of PDIP1, and a synthetic peptide containing this PCNA-binding motif was shown to bind PCNA by far-Western analysis. Northern analysis demonstrated that PDIP1 mRNA is present in a wide variety of human tissues. PDIP1 was found to be highly homologous to a previously identified protein, B12 [Wolf, F. W., Marks, R. M., Sarma. V., Byers, M. G., Katz, R. W., Shows, T. B. & Dixit, V. M. (1992) J. Biol. Chem. 267, 1317-1326], one of the early response genes induced by tumor necrosis factor alpha. PDIP1 synthesis can also be induced by tumor necrosis factor alpha and by IL-6, cytokines essential for liver regeneration after loss of hepatic tissue. It is suggested that PDIP1 provides a link between cytokine activation and DNA replication in liver as well as in other tissues.
Our study used data collected in Chung-Hsing Village to evaluate the relationship between hyperglycemia and its related factors in Taiwanese middle-aged adults in May 1998. All government employees at the Taiwan Provincial Government in Chung-Hsing Village aged 40-64 years were candidates for this study. Only 708 volunteers completed a structured questionnaire and underwent venous blood tests. To study the significant related factors of hyperglycemia, the t-test, chi(2) analysis and multivariate logistic regression were used. Our results showed that 40% of the 708 subjects were men and 60% were women. The mean age was 50.5 plus minus 6.8 years. The mean values of fasting glucose were 4.68 plus minus 1.92 mmol/L in men and 4.70 plus minus 1.70 mmol/L in women (P > 0.05). The proportions of hyperglycemia were 6.4% in men and 5.7% in women (P > 0.05). After controlling for other covariates, the multivariate logistic regression analysis showed that the significant related factors for hyperglycemia were older age (odds ratio=2.86, 95%; confidence interval=1.36-6.05; P < 0.01) and hypertriglyceridemia (odds ratio=3.34, 95%; confidence interval=1.68-6.64; P < 0.001).
Primary biliary cirrhosis (PBC) is well known to recur after liver transplantation (LT). The recurrence is usually subclinical and evident only on histological examination. Recently, a new entity of de novo autoimmune hepatitis (AIH) has emerged that occurs after LT in patients who underwent transplantation for diseases other than AIH. This new condition occurs more often in children; however, there was a recent report of the first 2 cases in adults who originally underwent LT for PBC. We report the first case of concurrent de novo AIH and recurrence of PBC documented on the liver biopsy of an adult patient who underwent LT for end-stage PBC. Unlike the earlier report of 2 adults, our patient manifested an antinuclear antibody titer of more than 1/800 from a previously negative titer pre-LT, as well as fulfilled the International AIH Group criteria for a definite diagnosis of AIH. PBC recurrence was evidenced by typical florid duct lesion, antimitochondrial antibody titer increasing from 1/40 to greater than 1/800, and an elevated serum immunoglobulin M level. After the addition of azathioprine to baseline immunosuppression of tacrolimus and prednisolone, the patient responded rapidly, with complete normalization of liver test results.
INTRODUCTION: A case of alpha-fetoprotein (AFP)-producing gastric cancer is described in a 57-year-old Chinese woman. CLINICAL PICTURE: She presented with bleeding tendency and bone pain, and was found to have haematological evidence of disseminated intravascular coagulation and spinal metastasis. Her tumour markers, including AFP, Ca 19-9 and carcinoembryonic antigen (CEA) were elevated. In view of the elevated tumour markers, there was an exhaustive search for a primary lesion in the gastrointestinal tract, liver and ovaries. There was no radiological evidence to suggest any lesion in the chest, liver or pelvis. Lectin affinity electrophoresis of the AFP showed AFP-L2 and AFP-L3 bands, which are suggestive of a non-hepatoma malignancy. MANAGEMENT: Gastroscopy showed a gastric ulcer and she developed bleeding after the gastric biopsy which required urgent surgery. Intraoperatively she was found to have carcinomatous peritone and a malignant ulcer in the greater curve of the stomach. Histology confirmed a linitis plastica like adenocarcinoma which stains for AFP. OUTCOME: She died from multi-organ failure 3 days after surgery. CONCLUSION: AFP-producing adenocarcinoma of the stomach is not uncommon. Lectin affinity electrophoresis of AFP is helpful in the differentiation between hepatoma and non-hepatoma malignancies.
A rickettsia-like organism isolated from infected, farm-reared Cherax quadricarinatus was cultured in the yolk sac of developing chicken eggs, but could not be cultured in 3 continuous cell lines, bluegill fry (BF-2), fathead minnow (FHM), and Spodoptera frugiperda (Sf-9). The organism was confirmed by fulfilling Koch's postulates as the aetiological agent of mortalities amongst C. quadricarinatus. When C. quadricarinatus was inoculated with the organism, mortality was 100% at 28 degrees C and 80% at an ambient temperature of 24 degrees C. Horizontal transmission with food and via the waterborne route was demonstrated, but mortalities were lower at 30 and 10% respectively over a 4 wk period. The 16S rRNA sequence of 1325 base pairs of the Gram-negative, obligate intracellular organism was 95.6% homologous to Coxiella burnetii. Of 18 species compared to this rickettsia, the next most closely related bacterium was Legionella pneumophila at 86.7%. The suggested classification of this organism is Order Rickettsiales, family Rickettsiaceae, tribe Rickettsieae, within the genus Coxiella. We suggest it should be named Coxiella cheraxi sp. nov.
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Hepatocellular carcinoma is often diagnosed at a late, inoperable stage for which there are no uniformly efficacious treatment available presently. The oral anti-oestrogen drug, tamoxifen, has been used in such patients, based on the belief that the growth of hepatocellular carcinoma is promoted by endogenous oestrogen via a receptor-mediated process. In this review, we examine the trials reported in the literature using tamoxifen in hepatocellular carcinoma. Randomized controlled trials with tamoxifen have so far revealed mixed results. We propose that this may be due to the fact that the mechanism of action of tamoxifen in hepatocellular carcinoma is via an oestrogen-receptor independent pathway that requires much higher doses of tamoxifen for activation than those used in the trials so far. Thus there must be a paradigm shift to dissociate the action of tamoxifen from oestrogen receptors in hepatocellular carcinoma. This means that future trials with tamoxifen in hepatocellular carcinoma should use higher doses of tamoxifen, at least four to eight-fold that of the dose that is efficacious in an oestrogen-receptor dependent mechanism.
BACKGROUND: Our study used data collected in the Chung-Shing-Shin-Tseun community of Taiwan in May 1998 to evaluate the distribution of fasting glucose and the relation between hyperglycemia and the cardiovascular risk factors and sociodemographic factors in elderly persons. METHODS: Individuals aged 65 and over were recruited as study subjects. A total of 1,093 persons, out of 1,774 registered residents, were contacted in face-to-face interviews. The response rate was 61.6%. However, only 586 respondents took blood tests and completed questionnaires. Analysis in this study was based on these 586 subjects. The t test, chi-square analysis, and multivariate logistic regression were used to study the significant correlates of hyperglycemia. RESULTS: Of the individuals in our study, 66.0% were men and 34.0% were women. The mean age was 73.1 +/- 5.3 years. The mean values of fasting glucose were 5.5 +/- 1.6 mmol/L in elderly men and 5.7 +/- 2.1 mmol/L in elderly women. The hyperglycemic rates determined by modified World Health Organization criteria (> or =6.05 mmol/L) were 20.2% in elderly men and 20.7% in elderly women. Multivariate logistic regression analysis was used, after controlling the other covariates, to show that the significant related factors in hyperglycemia were obesity (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.02-4.5), high systolic pressure (OR 2.1, 95% CI 1.1-4.0), and hypertriglyceridemia (OR 2.1, 95% CI 1.03-4.4). No significant association was found between hyperglycemia and gender, age, high diastolic pressure, abnormal glutamic pyruvic transaminase, hypercholesterolemia, hyperuricemia, renal function impairment, education level, retirement status, or marital status. CONCLUSIONS: The prevalence of hyperglycemia is high in elderly persons. Hyperglycemia is significantly associated with obesity, high systolic pressure, and hypertriglyceridemia in elderly persons. It is important to examine other cardiovascular risk factors if one cardiovascular risk factor is observed.