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Biomedical subjects

N Leung

Publications and source records attributed to N Leung.

At least 19 recordsLinked to original sources

Deletion of the carcinoembryonic antigen-related cell adhesion molecule 1 (Ceacam1) gene contributes to colon tumor progression in a murine model of carcinogenesis.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a glycoprotein that is part of the carcinoembryonic antigen and the immunoglobulin superfamilies. We have shown that it functions as a tumor suppressor and that this function depends upon the presence of the longer CEACAM1 cytoplasmic domain. In this report, we describe the generation of a Ceacam1-/- mouse. The Ceacam1-/- colon exhibits increased in vivo proliferation relative to the wild-type counterpart with a corresponding decreased expression of the p21(Cip1) and p27(Kip1) Cyclin D kinase inhibitors. The colonic villi undergo decreased apoptosis. Out of 35 litters of mice, no spontaneous tumors in any tissues normally expressing CEACAM1 were found over the lifespan of the animals, suggesting that CEACAM1 may not be involved in initiation of tumor development. However, when mice are treated with azoxymethane to induce colonic tumors, we find that Ceacam1-/- mice developed a significantly greater number of tumors than their littermate controls. Moreover, the tumor size was greater in the knockout mice relative to that in the wild-type mice. These results indicate that deletion of CEACAM1 favors progression of colon tumorigenesis.

Animals↗

48 weeks pegylated interferon alpha-2a is superior to 24 weeks of pegylated interferon alpha-2b in achieving hepatitis B e antigen seroconversion in chronic hepatitis B infection.

BACKGROUND/AIM: Although 48-week therapy with pegylated-interferons has been shown to be effective for the treatment of chronic hepatitis B virus infection, the efficacy of a shorter duration of therapy with pegylated interferons is unknown. METHOD: We reviewed 53 hepatitis B e antigen positive Chinese patients treated with 48 weeks of pegylated interferon alpha-2a or 24 weeks of pegylated interferon alpha-2b. Sustained virological response was defined as hepatitis B e antigen seroconversion and hepatitis B virus DNA <10(5) copies/mL at week 72. RESULTS: Twenty-nine patients were treated with 48 weeks of pegylated-interferon-alpha-2a and 24 patients with 24 weeks of pegylated-interferon-alpha-2b. At the end-of-therapy, hepatitis B e antigen seroconversion and hepatitis B virus DNA <10(5) copies/mL were similar between the two groups of patients [9/29 (31.0%) vs. 2/24 (8.3%), respectively, P = 0.09]. At week 72, 10 of the 29 patients (34.5%) treated with 48 weeks of pegylated-interferon-alpha-2a compared with two of the 24 patients (8.3%) treated with 24 weeks of pegylated-interferon-alpha-2b had sustained virological response (P = 0.04). By logistic analysis, 48 weeks of pegylated-interferon-alpha-2a was independently associated with sustained virological response (P = 0.04 adjusted hazards-ratio 9.37). CONCLUSION: Further studies are required to determine the optimal duration of therapy with pegylated interferons in chronic hepatitis B.

Adult↗

Core beliefs, recalled parental rearing and eating psychopathology across different age groups.

This study explored and compared the patterns of core beliefs, recalled parental rearing behaviours and eating psychopathology in non-clinical females of different ages; university staff and university students. No differences were found between the two age groups except that younger women had higher Drive for Thinness scores. However, core beliefs were associated with eating attitudes and behaviours in younger women and with recalled parental rearing behaviours in older women. The results suggest that younger women tend to externalise their negative core beliefs in the form of disordered eating behaviour whereas older women appear to express their dysfunctional core beliefs in ways other than weight and shape-related issues. The possible mechanisms behind these findings require further investigation.

Adult↗

Natural history of patients with recurrent chronic hepatitis C virus and occult hepatitis B co-infection after liver transplantation.

It is uncertain whether occult hepatitis B virus co-infection will hasten progressive liver disease in chronic hepatitis C patients after liver transplantation. This study evaluated fibrosis progression and severe fibrosis in 118 consecutive hepatitis B surface antigen-negative patients with virological and histological evidence of recurrent chronic hepatitis C infection co-infected with occult hepatitis B virus after liver transplantation. HBV DNA was detected from serum at the time of recurrent chronic hepatitis C infection by polymerase chain reaction. Each subject underwent a repeat liver biopsy 5 years post-liver transplantation. Occult hepatitis B virus co-infection was present in 41 of the 118 (34.7%) patients. At 5 years post-liver transplantation, 13 of the 41 occult hepatitis B virus co-infected patients compared with 16 of the 77 patients without occult hepatitis B virus co-infection developed fibrosis progression (31.7% vs. 20.8%, respectively, p = 0.39). Eight of 41 the occult hepatitis B virus co-infected patients compared with 13 of the 77 patients without occult hepatitis B virus co-infection had severe fibrosis (19.5% vs. 16.9%, respectively, p = 0.97). In conclusion, occult hepatitis B virus co-infection in patients with recurrent chronic hepatitis C infection was not associated with accelerated fibrosis progression or severe fibrosis after liver transplantation.

Adult↗

Hepatitis B reactivation after withdrawal of pre-emptive lamivudine in patients with haematological malignancy on completion of cytotoxic chemotherapy.

BACKGROUND: The hepatic outcome of hepatitis B surface antigen (HBsAg) positive patients undergoing chemotherapy after withdrawal of pre-emptive lamivudine is unknown. AIMS: To examine the occurrence of hepatitis B virus (HBV) reactivation after withdrawal of pre-emptive lamivudine. METHODS: Pre-emptive lamivudine was started one week before initiation of chemotherapy in 46 consecutive HBsAg positive patients and continued for the entire duration of chemotherapy. Pre-emptive lamivudine was stopped at a median 3.1 (range 3.0-3.4) months after completion of chemotherapy. Patients were longitudinally followed up after withdrawal of pre-emptive lamivudine. RESULTS: Median time of follow up after withdrawal of lamivudine was 25.7 (range 5.7-75.7) months. Eleven of the 46 patients (23.9%) developed HBV reactivation after withdrawal of pre-emptive lamivudine. Eight of the 16 patients with high pre-chemotherapy HBV DNA (> or =10(4) copies/ml) compared with three of the 30 patients with low pre-chemotherapy HBV DNA (<10(4) copies/ml) developed HBV reactivation (50.0% v 10.0%, respectively; p<0.001). Hepatitis B e antigen positive patients were also more likely to develop HBV reactivation (5/11 (45.5%) v 6/35 (17.1%), respectively; p = 0.041). A high pre-chemotherapy HBV DNA (> or =10(4) copies/ml) was the most important risk factor for HBV reactivation after withdrawal of pre-emptive lamivudine on Cox proportional hazards analysis (relative risk 16.13, (95% confidence interval 2.99-87.01; p = 0.001). CONCLUSIONS: HBV reactivation is more likely to occur in patients with high pre-chemotherapy HBV DNA after withdrawal of pre-emptive lamivudine. A more prolonged course of antiviral therapy may be necessary in these patients after completion of chemotherapy in order to reduce post-chemotherapy HBV reactivation.

Adult↗

Parental rearing behaviours and eating disorders: the moderating role of core beliefs.

OBJECTIVE: Core beliefs have been shown to mediate between eating psychopathology and dysfunctional parent-daughter interactions. However, the possible moderating role of core beliefs has been neglected. This study aimed to explore the hypothesis that core beliefs serve as moderator variables in the relationship between recalled parental rearing behaviours and eating psychopathology. METHOD: Sixty-six women with a current eating disorder completed self-report measures of parental rearing behaviours, core beliefs, and eating psychopathology. RESULTS: Three core beliefs were found to moderate the relationship between paternal rejection and aspects of eating psychopathology. The predictive validity of paternal rejection on aspects of eating symptomatology was found to decrease as dysfunctional core beliefs increased. DISCUSSION: When levels of social isolation, vulnerability to harm, and self-sacrifice core beliefs were high, recalled parental relationships were no longer relevant to current eating psychopathology. The findings provide further evidence that core beliefs are important factors in eating disorder psychopathology and may be clinically useful in identifying targets for treatment.

Adolescent↗

Prolonged increase of plasma non-esterified fatty acids fully abolishes the stimulatory effect of 24 hours of moderate hyperglycaemia on insulin sensitivity and pancreatic beta-cell function in obese men.

AIMS/HYPOTHESIS: A prolonged increase of plasma NEFA impairs acute glucose-stimulated insulin secretion (GSIS) in vitro and in vivo. Our study therefore examined the combined effect of increased plasma NEFA and glucose on GSIS in humans. METHODS: We examined GSIS on four occasions in eight obese men during a 10 mmol/l hyperglycaemic clamp and after a 24-h infusion of (i) normal saline, (ii) intralipid and heparin to raise plasma NEFA about two-fold above basal, (iii) 20% dextrose to raise plasma glucose to about 7.5 mmol/l and (iv) intralipid and heparin combined with 20% dextrose to raise plasma NEFA and glucose. RESULTS: In study (iii) insulin sensitivity was about 20% greater than in study (i) and the disposition index was about 50% higher. Insulin sensitivity tended to be lower in study (ii) whereas the disposition index was lower than in study (i), confirming previous observations. The combination of increased plasma NEFA and glucose (study iv) reduced insulin sensitivity in comparison with study (i) and completely abolished the increase in insulin sensitivity and disposition index seen in study (iii), but did not reduce the latter to a lower value than that in the saline control study (study i). CONCLUSIONS/INTERPRETATION: We showed that a prolonged increase of plasma NEFA completely abolishes the stimulatory effect of moderate hyperglycaemia on insulin sensitivity and beta-cell function in obese humans. This suggests that previous observations, showing that a prolonged increase of plasma NEFA impairs pancreatic beta-cell function, also apply to the hyperglycaemic state.

Blood Glucose↗

Somatoform dissociation in eating-disordered patients.

This study investigated the role of somatoform dissociation in eating disorders and pathological eating behaviour, relative to the established association of eating pathology with psychological dissociation. The participants were 131 women with DSM-IV diagnoses of anorexic or bulimic disorders and 75 women who had no such disorder. Each woman completed measures of psychological and somatoform dissociation, as well as a measure of bulimic attitudes. The current presence or absence of specific bulimic behaviours was identified during the clinical interview. Levels of both forms of dissociation were higher in the women who had diagnoses of disorders with a bulimic component (bulimia nervosa; anorexia nervosa of the binge/purge subtype) than in the non-clinical or restrictive anorexic women. Somatoform dissociation showed particularly strong links with the presence of bulimic behavioural features (excessive exercise, laxative abuse, diet pill abuse, diuretic abuse) and with bulimic attitudes. The formulation and treatment of cases where there are bulimic features is likely to be enhanced by the assessment of somatoform dissociation.

Adult↗

Core beliefs and bulimic symptomatology in non-eating-disordered women: the mediating role of borderline characteristics.

OBJECTIVE: To establish whether borderline personality disorder symptoms play a mediating role in the relationship between early maladaptive schemata and bulimic symptomatology, using a nonclinical sample. METHOD: Sixty-one female undergraduate students completed the Bulimic Investigatory Test, Edinburgh (BITE), the Borderline Syndrome Index (BSI), and the short form of the Young Schema Questionnaire (YSQ). RESULTS: Borderline symptoms were found to be a perfect mediator in the relationship between defectiveness/shame beliefs and bulimic symptomatology. CONCLUSIONS: A model is proposed suggesting that the functional utility of bulimic behaviors might be in counteracting the negative emotions associated with borderline symptoms.

Adolescent↗

Acute cholestatic liver disease protects against glycerol-induced acute renal failure in the rat.

BACKGROUND: It is widely held that liver disease predisposes toward acute tubular necrosis. The present study examines the effect of acute cholestatic liver disease on the susceptibility to glycerol-induced acute tubular necrosis in the rat. METHODS: Acute cholestatic liver disease was induced by ligation of the common bile duct, while the intramuscular injection of hypertonic glycerol was used to induce acute tubular necrosis. Renal injury was assessed by plasma creatinine concentration and renal histology. An in vitro model of heme protein-induced renal injury (hemoglobin in conjunction with glutathione depletion) was employed to assess the cytoprotective effects of bilirubin. RESULTS: Ligation of the common bile duct markedly reduced acute renal injury that occurs in the glycerol model (7.5 mL/kg body weight), as evidenced by a lower plasma creatinine concentration and less severe renal histologic injury. At a higher dose of glycerol (10 mL/kg body weight), ligation of the common bile duct again reduced renal injury and cumulative mortality that occurs five days after the induction of this model of acute renal failure. These protective effects of ligation of the common bile duct could not be ascribed to less severe muscle injury or red cell damage. Ligation of the common bile duct induced heme oxygenase-1 in the kidney and markedly so in the liver. Inhibition of heme oxygenase significantly attenuated, but did not prevent, the protective effects conferred by ligation of the common bile duct. Bilirubin, in low micromolar concentrations, was cytoprotective against heme protein-induced cell injury in vitro. CONCLUSIONS: Ligation of the common bile duct confers resistance to glycerol-induced acute tubular necrosis in the rat, actions that arise, in part, from the induction of heme oxygenase-1 in the kidney and liver. Bilirubin, in micromolar concentrations, protects against heme protein-induced renal injury. Our studies uncover a novel form of acquired resistance to renal injury, occurring, unexpectedly, in the setting of acute cholestatic liver disease. We speculate that such potentially cytoprotective alterations may safeguard the kidney against irreversible functional and structural injury in the hepatorenal syndrome.

Acute Kidney Injury↗

Outcome of group cognitive-behavior therapy for bulimia nervosa: the role of core beliefs.

It is hypothesized that individuals who benefit less from CBT will be those who have more pathological core beliefs (unconditional beliefs, unrelated to food, shape and weight). Twenty bulimic women were treated using 12 sessions of conventional group CBT. Eating behavior and attitudes were assessed pre- and posttreatment. Core beliefs were assessed at the beginning of the programme, and were used as predictors of change across treatment (once any effect of pretreatment psychopathology was taken into account). Group CBT was effective, with reductions of over 50% in bulimic symptoms. Outcome on most indices was associated with pretreatment levels of pathological core beliefs. Possible reasons for these findings are discussed.

Adolescent↗

Chronic hepatitis B virus infection in Asian countries.

Of the estimated 50 million new cases of hepatitis B virus (HBV) infection diagnosed annually, 5-10% of adults and up to 90% of infants will become chronically infected, 75% of these in Asia where hepatitis B is the leading cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC). In Indonesia, 4.6% of the population was positive for HBsAg in 1994 and of these, 21% were positive for HBeAg and 73% for anti-HBe; 44% and 45% of Indonesian patients with cirrhosis and HCC, respectively, were HBsAg positive. In the Philippines, there appear to be two types of age-specific HBsAg prevalence, suggesting different modes of transmission. In Thailand, 8-10% of males and 6-8% of females are HBsAg positive, with HBsAg also found in 30% of patients with cirrhosis and 50-75% of those with HCC. In Taiwan, 75-80% of patients with chronic liver disease are HBsAg positive, and HBsAg is found in 34% and 72% of patients with cirrhosis and HCC, respectively. In China, 73% of patients with chronic hepatitis and 78% and 71% of those with cirrhosis and HCC, respectively, are HBsAg positive. In Singapore, the prevalence of HBsAg has dropped since the introduction of HBV vaccination and the HBsAg seroprevalence of unvaccinated individuals over 5 years of age is 4.5%. In Malaysia, 5.24% of healthy volunteers, with a mean age of 34 years, were positive for HBsAg in 1997. In the highly endemic countries in Asia, the majority of infections are contracted postnatally or perinatally. Three phases of chronic HBV infection are recognized: phase 1 patients are HBeAg positive with high levels of virus in the serum and minimal hepatic inflammation; phase 2 patients have intermittent or continuous hepatitis of varying degrees of severity; phase 3 is the inactive phase during which viral concentrations are low and there is minimal inflammatory activity in the liver. In general, patients who clear HBeAg have a better prognosis than patients who remain HBeAg-positive for prolonged periods of time. The outcome after anti-HBe seroconversion depends on the degree of pre-existing liver damage and any subsequent HBV reactivation. Without pre-existing cirrhosis, there may be only slight fibrosis or mild chronic hepatitis, but with pre-existing cirrhosis, further complications may ensue. HBsAg-negative chronic hepatitis B is a phase of chronic HBV infection during which a mutation arises resulting in the inability of the virus to produce HBeAg. Such patients tend to have more severe liver disease and run a more rapidly progressive course. The annual probability of developing cirrhosis varies from 0.1 to 1.0% depending on the duration of HBV replication, the severity of disease and the presence of concomitant infections or drugs. The annual incidence of hepatic decompensation in HBV-related cirrhosis varies from 2 to 10% and in these patients the 5-year survival rate drops dramatically to 14-35%. The annual risk of developing HCC in patients with cirrhosis varies between 1 and 6%; the overall reported annual detection rate of HCC in surveillance studies, which included individuals with chronic hepatitis B and cirrhosis, is 0.8-4.1%. Chronic hepatitis B is not a static disease and the natural history of the disease is affected by both viral and host factors. The prognosis is poor with decompensated cirrhosis and effective treatment options are limited. Prevention of HBV infection thorough vaccination is still, therefore, the best strategy for decreasing the incidence of hepatitis B-associated cirrhosis and HCC.

Asia↗

Nucleoside analogues in the treatment of chronic hepatitis B.

Many nucleoside analogues have been investigated for the treatment of chronic hepatitis B. Some were withdrawn because of significant adverse effects and some are still in the early stage of clinical assessment. Lamivudine has been demonstrated to have consistent efficacy and safety in large-scale, phase III clinical trials. It has achieved a milestone in the treatment of chronic hepatitis B and is now commercially available in many countries. Being a potent inhibitor of hepatitis B viral replication, it achieved around 18% HBeAg seroconversion in HBeAg-positive patients after 1 year of therapy. HBeAg seroconversion is a good endpoint for therapy and has been shown to be 80% durable. The response was better among patients with raised pretreatment alanine aminotransferase levels. Liver necro-inflammation and fibrosis improved significantly after 1 year. Further improvement on extended therapy was observed together with an incremental increase in HBeAg seroconversion. Similar efficacy was demonstrated in HBeAg-negative viraemic patients. The main drawback is the emergence of drug-resistant variants starting from the sixth to ninth month of treatment. This can be associated with varying degrees of relapse of disease activity and may offset the benefit of therapy. With extended therapy, drug-resistant variants continue to emergence at a rate of around 20% per year. Adefovir dipivoxil and entacavir are nucleoside or nucleotide analogues shown to suppress both the wild-type and lamivudine-resistant virus. Combination of these nucleoside/nucleotide analogues with immune modulators may be the answer to eradicate the virus in short-term therapy and avoid the issue of drug resistance.

2-Aminopurine↗

The relationship between parental bonding and core beliefs in anorexic and bulimic women.

OBJECTIVE: The role of core beliefs in the psychopathology of eating disorders has been considered in recent years. Young (1994) hypothesized that unhealthy core beliefs originate from the experience from the first few years of life. The aim of the present study was to consider whether perceived parental bonding might explain the development of such beliefs in eating disordered women. METHOD: The participants were 30 anorexics, 27 bulimics and 23 comparison women who completed measures of core beliefs and perceived parental bonding. RESULTS: There were significant differences in perceived parental bonding behaviours across groups. The association between parental bonding and core beliefs were much stronger in the anorexic group than that in either the bulimic or the control group. In particular, a perceived low level of parental care was predictive of the presence of some unhealthy core beliefs in anorexic women. CONCLUSION: Longitudinal research is needed to confirm these findings among anorexic and bulimic women. Clinically, these findings provide insight into the possible origins or core beliefs, and hence might aid their challenge in schema-focused cognitive therapy.

Adolescent↗

Liver disease-significant improvement with lamivudine.

The natural history of chronic hepatitis B virus (HBV) infection is highly variable, ranging from a benign course to one of shortened life expectancy. Liver histology represents an accurate tool for assessing progressive liver disease, and has been used in five recent Phase III clinical trials of the oral nucleoside analogue, lamivudine, 100 mg/day, in patients with chronic hepatitis B. Significant improvements in the Knodell histological activity index (HAI) score were reported with lamivudine, with greater decreases noted after 2 years of therapy, consistent with continued alanine transaminase (ALT) normalisation. Histological data showed that lamivudine therapy can resolve or lessen the progression of fibrosis, and reduce the progression to cirrhosis in patients with chronic hepatitis B. These trials also showed that lamivudine provoked significant enhancement of hepatitis B e antigen (HBeAg) seroconversion compared with placebo, and had a profound effect on serum HBV DNA, resulting in rapid suppression of viraemia. The emergence of variants with a mutation in the YMDD (tyrosine-methionine-aspartate-as-partate) motif did not cause significant worsening of the Knodell HAI score. In conclusion, lamivudine is the first oral antiviral therapy for the treatment of chronic hepatitis B. It reduces significantly the severity of liver disease and reduces progression to cirrhosis. In addition, because lamivudine is well tolerated it represents a viable therapeutic option that may improve the prognosis of patients with chronic hepatitis B.

Antiviral Agents↗

Core beliefs in anorexic and bulimic women.

There is research evidence to suggest the presence of dysfunctional cognitions in anorexia nervosa and bulimia nervosa that are not related to food, weight, or shape. These maladaptive cognitions have not been addressed by the conventional cognitive behavioral models of etiology or therapy. This study aimed to assess the impact of unhealthy core beliefs on eating disorders and their symptoms. Twenty restricting anorexics, 10 bulimic anorexics, 27 bulimics, and 23 normal controls completed Young's Schema Questionnaire. Eating behaviors and attitudes were also measured. The results indicate that both anorexic and bulimic women had significantly higher levels of unhealthy core beliefs than comparison women, but the clinical groups only differed on one individual core belief (entitlement). However, there were different patterns of association between core beliefs and eating psychopathology in anorexic and bulimic women. It is suggested that future clinical practice should incorporate core beliefs as a potential element in the assessment and treatment of eating disorders.

Adolescent↗