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Biomedical subjects

M Cheang

Publications and source records attributed to M Cheang.

At least 19 recordsLinked to original sources
PubMed2006

Kidney transplantation outcomes in Canadian aboriginals.

Aboriginal populations experience a very high rate of end-stage renal disease (ESRD); however, little is known about the outcomes of transplantation in this population. We performed a retrospective database review to determine the short- and long-term outcomes of kidney transplantation in Aboriginals. Adult Aboriginal (AB) and Caucasian (C) individuals receiving primary kidney transplants between 1969 and 2003 in Manitoba, Canada were examined. A total of 705 recipients were included (126 AB and 579 C). AB recipients were younger, had different etiologies of ESRD, longer cold-ischemic times for deceased donor transplants, and higher peak panel reactive antibody levels. At 1 year post-transplant, there was no difference in serum creatinine, acute rejection or graft survival between AB and C recipients. However, AB recipients experienced greater weight gains early post-transplant and were more likely to develop post-transplant diabetes mellitus. AB recipients exhibited inferior 10-year graft (AB 26% vs. C 47%, p < 0.01) and patient survival (AB 50% vs. 75%, p < 0.01). When graft survival was censored for death with a functioning graft, there was no difference between the two groups. Multivariate analysis revealed AB race to be an independent predictor of premature graft failure and patient death. In conclusion, kidney transplant outcomes have historically been inferior in the Manitoba population of Canadian Aboriginals.

Adult↗
PubMed2004

Evaluation of immunohistochemical markers in non-small cell lung cancer by unsupervised hierarchical clustering analysis: a tissue microarray study of 284 cases and 18 markers.

This study has investigated a panel of immunomarkers in non-small cell lung carcinoma (NSCLC). Unsupervised hierarchical clustering analysis was used to investigate the possibility of identifying different subgroups in NSCLC based on their molecular expression profile rather than morphological features. A tissue microarray consisting of 284 cases of NSCLC was constructed. Immunohistochemistry was used to detect the presence of 18 biomarkers including synaptophysin, chromogranin, bombesin, NSE, GFI1, ASH-1, p53, p63, p21, p27, E2F-1, cyclin D1, Bcl-2, TTF-1, CEA, HER2/neu, cytokeratin 5/6, and pancytokeratin. Univariate analysis of all 18 markers for prognostic significance was performed. Immunohistochemical scoring data for NSCLC were analysed by unsupervised hierarchical clustering analysis. Kaplan-Meier survival curves were plotted for the different cluster groups of lung tumours identified by this method. Analysis of the three different World Health Organization (WHO) subtypes (adenocarcinoma, squamous cell carcinoma, large cell carcinoma) of NSCLC individually showed that different markers were significant in different subtypes. For example, p53 and p63 were significant for squamous cell carcinoma (p = 0.007 and p = 0.03, respectively), whereas cyclin D1 and HER2/neu were significant prognostic markers for adenocarcinoma (p = 0.025 and p = 0.015, respectively). These markers were not significant prognostic predictors for NSCLC as a group. Hierarchical clustering analysis of NSCLC produced four separate cluster groups, although the vast majority of cases were found in two cluster groups, one dominated by squamous cell carcinoma and the other by adenocarcinoma. The clinical outcomes of cases from the four cluster groups were not significantly different. Prognostic indicators vary between different morphological subtypes of NSCLC. Unsupervised hierarchical clustering analysis, based on an extended immunoprofile, identifies two main cluster groups corresponding to adenocarcinoma and squamous cell carcinoma; cases of large cell carcinomas are assigned to one of these two groups based on their molecular phenotype.

Adenocarcinoma↗
PubMed2004

P63 expression in lung carcinoma: a tissue microarray study of 408 cases.

p63 is a recently discovered member of the p53 family that has been shown to be important in the development of epithelial tissues. p63 may also play a role in squamous cell carcinomas of the lung, head and neck, and cervix, and its expression is increased in these tumors. The purpose of this study was to investigate the expression of p63 in a broad spectrum of histologic types of lung tumors. A total of 441 cases of primary lung tumors with follow-up data were identified, and the paraffin-embedded tissue blocks were used to construct a duplicate core tissue microarray. After review of the tissue cores, 408 cases, consisting of 123 squamous cell carcinomas, 93 adenocarcinomas, 68 large cell carcinomas, 68 classic carcinoids, 31 atypical carcinoids, 11 large cell neuroendocrine carcinomas, and 14 small cell carcinomas, were adequate for analysis. Immunohistochemistry was performed at 2 different laboratories using monoclonal antibody 4A4 to detect the expression of p63, using different staining protocols. p53 expression was also studied with immunohistochemistry using monoclonal antibody DO-7. Kaplan-Meier curves were plotted to compare the survival of p63-expressing versus nonexpressing tumors. A large proportion of squamous cell carcinomas expressed p63 (96.9%), most showing strong positive nuclear immunoreactivity. Expression in other nonsmall cell lung cancers was also present. Thirty percent of adenocarcinomas and 37% of large cell carcinomas showed p63 expression. In the neuroendocrine tumors, an increasing proportion of tumors stained for p63 as tumor grade increased; 1.9% of classic carcinoids, 30.8% of atypical carcinoids, 50% of large cell neuroendocrine carcinomas, and 76.9% of small cell carcinomas were positive. Approximately half of the positively staining neuroendocrine cases showed strong staining. Expression of p63 was of prognostic significance in neuroendocrine tumors (P < 0.0001), with higher-grade tumors more likely to express p63. Correlation between p63 and p53 expression was not observed (P = 0.18) in nonsmall cell lung cancer; however, a significant correlation between the 2 markers was found in neuroendocrine tumors (P < 0.0001). p63 staining was repeated with a different staining protocol, yielding similar results overall but a lower percentage of positive cases (34.2% vs. 48.4% of tumors positive). In conclusion, p63 expression is consistently expressed in squamous cell carcinoma in the lung, but is also expressed in a subset of adenocarcinomas and large cell carcinomas. Pulmonary neuroendocrine tumors also show p63 staining in some instances, particularly in higher-grade tumors, and the majority of small cell carcinomas are p63-positive. These results suggest that p63 may be involved in oncogenesis in a broader range of tumors than was previously thought.

Adenocarcinoma↗
PubMed2002

HLA-A and HLA-B in Kenya, Africa: allele frequencies and identification of HLA-B*1567 and HLA-B*4426.

HLA-A and HLA-B alleles of a population from Kenya, Africa were examined by sequencing exon 2 and exon 3 DNA and typing using a Taxonomy-based Sequence-analysis (TBSA) method. Extensive diversities were observed at both HLA-A and HLA-B loci in this population. Forty-one HLA-A alleles were identified from 159 unrelated individuals. The most frequently observed alleles were A*6802 (11.64%), A*02011/09 (9.75%), A*7401/02 (9.43%), A*3001 (7.86%), A*3002 (7.23%) and A*3601 (6.6%). Forty-nine HLA-B alleles were identified in 161 unrelated individuals, including two novel alleles, B*1567 and B*4426. The most frequently observed HLA-B alleles were B*5301 (9.01%), B*5801 (8.38%), B*4201 (7.76%), B*1503 (7.14%), B*1801 (6.21%), and B*5802 (5.90%). The most frequently observed HLA-A-B haplotypes were A*3601-B*5301 (3.55%) and A*3001-B*4201 (3.19%), followed by A*7401/02-B*5801 (2.84%), A*7401/02-B*5802 (2.84%) and A*02011/09-B*1503 (2.13%). Linkage disequilibrium and chi2 analysis showed the association of these HLA-A-B haplotypes at the antigen level to be significant. The frequencies of HLA-A and HLA-B alleles from the Kenyan population were compared with that of a population from Cameroon. The difference in allele and haplotype frequency distributions partly reflected the different ethnic composition of these two African populations.

Adult↗
PubMed2002

Fractal or biologically variable delivery of cardioplegic solution prevents diastolic dysfunction after cardiopulmonary bypass.

OBJECTIVE: To determine whether myocardial protection is improved by restoring physiologic variability to the cardioplegia pressure signal during cardiopulmonary bypass, we compared cardiac function in pigs in the first hour after either conventional cold-blood cardioplegia (group CC) or computer-controlled biologically variable pulsatile cardioplegia (group BVC). METHODS: Invasive monitors and sonomicrometry crystals were placed, and cardiopulmonary bypass was initiated. The aorta was crossclamped, and cold blood cardioplegic solution was infused intermittently through the aortic root with either conventional cardioplegia (n = 8) or biologically variable pulsatile cardioplegia (n = 8; mean pressure, 75 mm Hg for 85 minutes). The crossclamp was released, cardiac function was restored, and separation from cardiopulmonary bypass was completed. With stable temperature and arterial blood gases, hemodynamics and systolic and diastolic indices were compared at 15, 30, and 60 minutes after cardiopulmonary bypass. RESULTS: Diastolic stiffness doubled from 0.027 +/- 0.016 mm Hg/mm (mean +/- SD) at baseline to 0.055 +/- 0.036 mm Hg/mm (P =.003) at 1 hour after bypass in group CC, associated with increased left ventricular end-diastolic pressure from 9 +/- 2 to 11 +/- 2 mm Hg (P =.001), mean pulmonary artery pressure from 14 +/- 2 to 20 +/- 3 mm Hg (P =.003), and serum lactate levels from 2.0 +/- 0.5 to 5.6 +/- 2.3 mmol/L (P =.008). Systolic function was not affected. In group BVC diastolic stiffness, left ventricular end-diastolic pressure, and pulmonary artery pressure values were not different from control values at any time after bypass, and serum lactate levels were significantly less than with conventional cold blood cardioplegia. Peak pressure variability with biologically variable pulsatile cardioplegia fit a power-law equation (exponent = -3.0; R(2) = 0.97), indicating fractal behavior. CONCLUSION: Diastolic cardiac function is better preserved after cardiopulmonary bypass with biologically variable pulsatile cardioplegia and fractal perfusion. This may be attributed to enhanced microcirculatory perfusion with improved myocardial protection. A model supporting these results is presented.

Animals↗
PubMed2002

Mental disorders and public safety of the community at large--does the Tarasoff principle apply in Singapore?

The Tarasoff Principle is a legal ruling arising out of the Tarasoff case in California, in which 2 therapists were found by a court to be negligent for not warning an intended victim of a threat to her by their mentally disordered patient, and she was subsequently killed. The 2 therapists were deemed to have an obligation to protect an intended victim of a patient who presented a serious danger of violence. The question is whether this would apply under Singapore law, and whether an act of disclosure to protect a victim would be a breach of confidentiality and the doctor-patient relationship.

Humans↗
PubMed2001

Evaluation of primary hemostasis in neonates with a new in vitro platelet function analyzer.

With the use of the PFA-100 platelet function analyzer to evaluate primary hemostasis in whole blood, measured as closure time (CT), neonates had shorter CTs than members of an adult control group. Multivariate analysis of measures that contribute to primary hemostasis showed that higher hematocrits and increased ristocetin cofactor activity were the best correlates for CTs of cord blood. These 2 factors may also enhance primary hemostasis in vivo and compensate for the impaired platelet function of the newborn.

Adult↗
PubMed1999

Association of Chlamydia trachomatis heat-shock protein 60 antibody and HLA class II DQ alleles.

A total of 113 female commercial sex workers had individual alleles for HLA class II genes determined by using labeled sequence-specific oligonucleotide probes to hybridize to polymerase chain reaction products of amplified DNA. Women also had microimmunofluorescent (MIF) antibody titers to Chlamydia trachomatis elementary bodies and ELISA antibody to recombinant chlamydial heat-shock protein 60 (Chsp60) determined. Women were prospectively followed at monthly intervals over 2 years for incident C. trachomatis infection and acute pelvic inflammatory disease (PID). HLA DQA1*0401 and DQB1*0402 alleles were statistically associated with increased prevalence and amount of antibody to Chsp60 but not MIF antibody. However, these alleles did not alter the risk for chlamydial PID. The potential role that HLA DQ may play in chlamydial disease pathogenesis requires further study.

Antibodies, Bacterial↗
PubMed1999

Herpes zoster and multiple sclerosis.

BACKGROUND: Clinical experience suggests that young multiple sclerosis patients may have herpes zoster (HZ) earlier and more often than the general population. As there is evidence of a relationship between varicella zoster virus (VZV) and MS, a study of HZ and MS was undertaken. METHODS: Eight hundred and twenty-nine patient-members of the Manitoba Chapter of the Canadian Multiple Sclerosis Society were surveyed by mail. Six hundred and thirty-three (76%) responded. Questions included: age at diagnosis of MS, history of HZ (yes, no, probably), number of episodes of HZ and age at each occurrence, date of birth, and sex of respondent. The controls were consecutive patients with other neurological diseases (OND) attending local neurological or neurosurgical clinics, plus practice-based and population-based surveys of herpes zoster without reference to any other disease. The OND controls were assessed at the time of their outpatient visits. RESULTS: In the MS group with a positive/probable history of HZ, the HZ/MS rate was 106/633 (16.8%); in the practice-based survey the rate was 192/3534 (5.4%); and among the patients with OND it was 42/616 (6.8%). The HZ occurred at an earlier age in the MS group. The majority of male patients had HZ prior to the diagnosis of MS. The date of diagnosis is more likely to be a precise memory as opposed to the onset of symptoms. More than one attack of HZ was also more common in the MS group. CONCLUSIONS: This survey adds to the evidence that patients with MS have a unique relationship with the herpes zoster virus.

Adolescent↗
PubMed1998

Beneficial effects of treatment of early subclinical rejection: a randomized study.

The prevalence of subclinical rejection, by the Banff criteria, is approximately 30% in the first 3 mo in renal transplant recipients. A randomized study was performed to determine whether the treatment of subclinical rejection with corticosteroids was associated with improved outcomes in these patients. Seventy-two patients, stratified by donor source, were randomized to biopsies at 1, 2, 3, 6, and 12 mo (Biopsy group), or to 6- and 12-mo biopsies only (Control group). Patients were analyzed by "intent to treat" and were followed for a minimum of 2 yr. Patients in the Biopsy arm of the study had a significant decrease in early (months 2 and 3) and late (months 7 to 12) acute rejection episodes, a reduced chronic tubulointerstitial score at 6 mo, and a lower serum creatinine at 24 mo than did patients in the Control arm. There was a trend toward an increase in infectious morbidity, but no increase in mortality, in the patients randomized to the Biopsy group. The results of this study suggest that early protocol biopsies and the treatment of subclinical rejection with corticosteroids may lead to better histologic and functional outcomes in renal transplant recipients.

Biopsy↗
PubMed1998

Identification of clinical and histopathologic risk factors for diminished renal function 2 years posttransplant.

The aim of this study was to identify early clinical and pathologic variates that independently predict diminished renal allograft function at 24 mo posttransplant. A clinical pathologic data base was prospectively derived from 71 patients in whom protocol renal biopsies were performed at 1, 2, 3, 6, and 12 mo posttransplant. The major end point was the 24-mo serum creatinine. Variates correlating independently (r2 = 0.67) with the 24-mo serum creatinine were the chronic biopsy scores (months 3 and 6), late rejections (months 4 to 6), cyclosporin A (CsA) levels (months 1 to 2), and delayed graft function. The adjusted odds ratio (OR) and 95% confidence interval (CI) for having a serum creatinine > or = 130 mumol/L at 24 mo increased for every year the donor age increased (OR = 1.07; 95% CI, 1.02 to 1.13; range, 9 to 55) or for each late rejection episode (OR = 5.9; 95% CI, 1.7 to 20.1), whereas a mean CsA level > 300 micrograms/L from months 1 to 3 was protective (OR = 0.07; 95% CI, 0.01 to 0.43). Variates correlating independently (r2 = 0.53) with the change in serum creatinine from 6 to 24 mo (delta Cr6-24) were the chronic biopsy scores at months 3 and 6. The adjusted OR of the delta Cr6-24 rising > or = +20 mumol/L increased for every year the donor age increased (OR = 1.09; 95% CI, 1.02 to 1.16; range 9 to 56) or when the 6-mo chronic biopsy score was > or = 2 (OR = 6.6; 95% CI, 1.2 to 36.4). An estimate of the relative risk for diminished renal function at 2 yr can be assigned within 6 mo of transplant based on chronic pathology, late acute rejections, CsA levels, and donor age.

Adult↗
PubMed1998

Juvenile rheumatoid arthritis in a Canadian First Nations (aboriginal) population: onset subtypes and HLA associations.

OBJECTIVE: To determine onset subtypes and HLA associations of juvenile rheumatoid arthritis (JRA) in a First Nations (aboriginal) population; to determine whether population frequencies of HLA antigens may explain the distribution of subtypes of JRA in this population. METHODS: All patients were children from Manitoba and Northwestern Ontario seen in a single pediatric rheumatology clinic between 1975 and 1996. Patients were identified from a clinic registry. Controls were adults of Algonkian Cree and Ojibway heritage. Class I and II major histocompatibility (HLA) typing was performed for First Nations patients and controls. RESULTS: There were a total of 74 First Nations patients with JRA. The relative frequency of rheumatoid factor (RF) positive polyarticular JRA was higher and that of pauciarticular JRA was lower in First Nations compared with Caucasian patients (42 versus 3% and 22 versus 58%, respectively; p = 0.00000). HLA-DRB1*04 (63%), 08 (43%), and 1402 (25%) were the most common DRB1 antigens among controls. The main subtypes of DRB1*04 were 0404 (33% of controls) and 0407 (23%). HLA typing was performed for 39 First Nations patients; 27 were Cree or Ojibway, 4 were from other tribes, and 8 were part First Nations. Among Cree and Ojibway, 59% of controls and 63% of patients with RF positive polyarticular JRA (n = 16) had HLA-DRB1 antigens bearing the rheumatoid arthritis (RA) shared epitope (OR 1.16, 95% CI: 0.38, 3.48). The OR for polyarticular RF positive JRA in those with DRB1*0802 and 0901 were 0.15, 95% CI: 0.02; and 1.24 and 5.83, 95% CI: 1.58, 28.38, respectively. CONCLUSION: There was a high frequency of the RA shared epitope represented by both HLA-DRB1*0404 and 1402 in this Algonkian population. This high frequency may explain the high frequency of RF positive polyarticular JRA. DRB1*0802 may be protective, whereas DRB1*0901 may increase the risk for this subtype of JRA.

Adult↗
PubMed1998

HLA associations of seropositive rheumatoid arthritis in a Cree and Ojibway population.

OBJECTIVE: To determine the HLA associations of seropositive rheumatoid arthritis (RA) in a Cree and Ojibway population; to determine whether specific alleles distinguish juvenile or adult onset. METHODS: HLA-A, B, C, and DRB1 alleles were analyzed in 23 Ojibway and Cree patients with RA seen in a single tertiary care center. Comparisons were made with published results of controls and with results of 18 patients with rheumatoid factor (RF) positive polyarticular juvenile rheumatoid arthritis (JRA) from the same population. RESULTS: Comparisons among patients with RA, patients with RF positive polyarticular JRA, and controls showed increased frequencies of the RA shared epitope in patients with RA and of DRB1*0901 in patients with seropositive polyarticular JRA, while the frequency of DRB1*08 alleles was decreased in patients with RF positive polyarticular JRA. CONCLUSION: In this population, DRB1*0901 may promote while DRB1*08 alleles may protect against a juvenile onset of RA specifically. In contrast, the RA shared epitope may have a greater effect on the risk of adult onset seropositive RA. Due to the small patient numbers, these results require confirmation.

Adult↗
PubMed1997

The varicella zoster virus: a pilot trial of a potential therapeutic agent in multiple sclerosis.

There are a number of similarities in the geographic, latitudinal, and epidemiological features of multiple sclerosis (MS) and varicella (V). In the experimental model of MS, repeated high antigen doses (myelin basic protein) have deleted both the clinical and pathological manifestations of the disease. Therefore, it seemed appropriate to explore the effects of varicella zoster vaccine on patients with MS. Fifty patients with chronic progressive MS were vaccinated with attenuated varicella virus vaccine and followed for one year. Fourteen patients improved, four became worse, and twenty-nine were unchanged. All patients were seropositive for varicella before vaccination and all had a rise in varicella antibodies after the vaccinations. There were no major untoward results from the vaccine. Four patients developed mild chicken-pox after vaccination. This was a short-term pilot trial without control subjects. Thus, the apparently favourable clinical and magnetic imaging changes must be assessed with caution, as must the lack of adverse effects.

Adult↗
PubMed1997

Common infectious diseases in a population with low multiple sclerosis and varicella occurrence.

A previous study revealed the rarity of varicella zoster virus (VZV) diseases among 5601 Hutterite Brethren living in a high-risk area for these diseases. The current study was established to determine the frequency of other common infectious diseases. The information was gathered from a population-based study of a unique group of Manitoba citizens and compared with an equal number of their age and sex-matched neighbors. The data were contained in the records of the Manitoba Health Services Commission (MHSC). The MHSC, the sole paying agency for medical diseases in Manitoba, contained 94,383,972 records for all of Manitoba for the years 1985 to 1991 inclusive. From these, the records of a cohort of 5601 Hutterites and an equal number of non-Hutterite age- and sex-matched controls were examined for the frequency of 14 diseases of interest. To be eligible a Hutterite subject must have one of the 22 unique family names and live on a Colony with the precise address. A control must be age (within 10 years) and sex-matched, live in the same or a contiguous postal code, and use the same medical practitioners. There were no interventions or identification of any member of the study. Mumps, acute coryza, and rubella are of the same frequency among the two groups. Only herpes simplex and cellulitis are more common among the Hutterites. All of the other nine common infectious diseases are significantly more common among the controls. The VZV diseases are not exclusively less common among the Hutterite Brethren. Nine other common infectious diseases are also less common but the degree of significant difference does not reach the level of the VZV diseases. The reduction in numbers of these diseases among the Hutterites is not related to the vaccination habits of the group and is not due to physical isolation. The Hutterites appear to have a more effective immune system relative to their neighbors.

Age Factors↗
PubMed1997

Varicella zoster antibodies after herpes zoster, varicella and multiple sclerosis.

BACKGROUND: We previously showed that Manitoba Hutterites seek physician care for varicella zoster virus infection significantly less than non-Hutterites. The current study was undertaken to measure varicella zoster virus seroprevalence for Hutterite and non-Hutterite controls. METHODS: Blood was obtained from 315 Hutterites and 259 similar age and sex controls at the time of blood donations to The Canadian Red Cross Society. The controls were from the same or a contiguous postal code area and were collected at the same time as the Hutterite samples. The immune status of the specimens was determined by the ELISA method (enzyme linked immunosorbent assay). RESULTS: Twenty-eight per cent of 315 Hutterites had no immunity and an additional 25% had only marginal immunity. Among the 259 controls, 10% had no immunity and an additional 10% had only marginal immunity (p < .0001). CONCLUSIONS: Manitoba Hutterites have significantly decreased seroprevalence to varicella zoster virus infection. This study of serum varicella zoster virus antibodies verifies a previous population based study that demonstrated the relative rarity of varicella and herpes zoster among a particular population group.

Adult↗
PubMed1997

Quantification of the placebo response in ulcerative colitis.

BACKGROUND & AIMS: There is consistently a measurable benefit noted among placebo users in treatment trials of ulcerative colitis (UC). The aim of this study was to define the placebo response in active UC and identify study features that influence the placebo response. METHODS: MEDLINE database was searched for placebo-controlled treatment studies of active UC. Data extraction was performed by two reviewers, and one separate investigator reviewed all trials and data extraction before data tabulation. Placebo remission and benefit rates were determined for clinical, endoscopic, and histological outcomes. Synthesis analysis on the weighted proportions from the different studies explored the placebo response as it related to eight study variables. RESULTS: Thirty-eight of 44 studies identified were included in the analysis. The clinical remission rate was 9.1% (confidence interval [CI], 6.6-11.6) and the benefit rate was 26.7% (CI, 24.1-29.2). Similar rates were observed endoscopically and histologically. The number of study visits (< or =3 vs. >3) modified placebo response as assessed by clinical benefit (P = 0.05), endoscopic remission (P = 0.02), and histological remission (P = 0.04). Other study variables were not significant placebo response modifiers. CONCLUSIONS: In trials of active UC, the placebo remission rate is approximately 10% and the placebo benefit rate is approximately 30%. These rates are consistent regardless of assessment end point. The placebo response is greater in trials with more frequent study visits (more than three).

Colitis, Ulcerative↗