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Biomedical subjects

E Ng

Publications and source records attributed to E Ng.

At least 37 records · Page 2Linked to original sources

Superiority of yeast over bacterial cytosine deaminase for enzyme/prodrug gene therapy in colon cancer xenografts.

The enzyme/prodrug strategy using bacterial cytosine deaminase (bCD) and 5-fluorocytosine (5-FC) is currently under investigation for cancer gene therapy. A major limitation for the use of bCD is that it is inefficient in the conversion of 5-FC into 5-fluorouracil. In the present study, we show that the K(m) of yeast cytosine deaminase (yCD) for 5-FC was 22-fold lower when compared with that of bCD. HT29 human colon cancer cells transduced with yCD (HT29/yCD) were significantly more sensitive to 5-FC in vitro than HT29 cells transduced with bCD (HT29/bCD). In tumor-bearing nude mice, complete tumor regression was observed in 6 of 13 HT29/yCD tumors in response to 5-FC treatment (500 mg/kg i.p. daily, 5 days a week for 2 weeks), whereas 0 of 10 HT29/bCD tumors were cured. Our study demonstrates an improved efficacy of the CD/5-FC treatment strategy when yCD was used. This enzyme has, therefore, a high potential to increase the therapeutic outcome of the enzyme/prodrug strategy in cancer patients.

Animals↗

Bone mineralization at the callotasis site after completion of lengthening.

We studied the course of bone mineralization of regenerate bone after callotasis lengthening. Twenty-three patients (eight boys) (mean age at operation 11.5 years, range 4-17 years; leg length discrepancy [LLD] at surgery ranging from 4 to 13 cm) underwent dual-energy X-ray absorptiometry (DEXA) scanning weekly during the distraction phase, at 2 week intervals until removal of the fixator, and at the time of their out-patient visits thereafter, for a mean of 794 +/- 420 days after removal of the apparatus. At removal of the fixator, the bone mineral content (BMC) of the regenerate was nearly 70% of the normal contralateral limb. With time, this value gradually increased, and tended to reach normal values, with no significant difference between femur and tibia. With time, the BMC of the regenerate tends to return to the value of the normal contralateral limb. Probably, once the limb length discrepancy has been equalized, the mechanical stimuli imparted through weight-bearing to the lengthened limb are of the same magnitude bilaterally. In this instance, then, the newly formed bone, responding to these physical stimuli, would normalize its mineral content, confirming that bone remodeling continues well after lengthening is terminated. Mineralization of the regenerate after completion of the lengthening process reaches values significantly greater than at removal of the fixator, with an increase of >50% of the prelengthening values, regardless of the underlying pathology. The final value of this increased BMC is not significantly different than in the normal contralateral unoperated limb. At least part of the increase in bone mineralization following callotasis lengthening is due to the normal process of growth and development.

Absorptiometry, Photon↗

Self-expandable metal stents for malignant dysphagia.

BACKGROUND: The use of self-expandable metal stents in relieving dysphagia for patients with incurable malignant oesophageal strictures was retrospectively evaluated. METHODS: Between September 1993 and August 1996, 66 male and 16 female patients with a median age of 72 years received self-expandable metal stents for malignant dysphagia. Six patients had concurrent tracheo-oesophageal fistulas. All patients were stented under sedation and stent insertion was performed under fluoroscopic guidance. RESULTS: Stent placement was successful in 80 patients (98%). There were seven early complications (inaccurate positioning (n = 3), migration (n = 1), incomplete expansion (n = 1), intractable pain (n = 1), and perforation (n = 1)). Two complications were lethal and three were treated endoscopically. Mean dysphagia grade improved from 3.2+/-0.7 to 1.8+/-0.9 (P < 0.05) after implantation. All tracheo-esophageal fistulas were successfully occluded. Upon a median follow-up of 8 weeks (range: 2-20 weeks), 30 complications developed in 21 patients (tumour overgrowth (n = 15), food bolus obstruction (n = 7), tumour ingrowth (n = 2), buckling of stent (n = 2), tracheo-esophageal fistula (n = 2), bleeding (n = 1), and gastric wall herniation through metal coils (n = 1)). Median survival was 13 weeks (range: 1-82 weeks). CONCLUSION: Self-expandable metal stents provide useful palliation in patients with incurable malignant dysphagia.

Adenocarcinoma↗

Altered expression of p53 and mdm-2 proteins at diagnosis is associated with early treatment failure in childhood acute lymphoblastic leukemia.

PURPOSE: To determine whether potential alteration in p53 function through p53 gene mutation or mdm-2 overexpression correlates with early treatment failure in childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Diagnostic marrow samples from 34 children were analyzed for p53 gene alterations by western blot and SSCP/DNA sequence analysis and for mdm-2 overexpression by western blot analysis. These samples were derived from two groups of children with ALL: 17 good outcome patients who are in long-term continuous complete remission and 17 poor outcome patients who did not achieve a complete remission or relapsed within 6 months of achieving remission. RESULTS: Two children within the poor outcome group were found to have p53 gene mutations. Furthermore, five poor outcome patients were shown to have greater than 10-fold overexpression of mdm-2 protein compared with the mean level of mdm-2 protein measured in the good outcome group. Aberrant p53 protein expression was found in only one good outcome patient, whereas no good outcome children were found to have elevated levels (> 10-fold) of mdm-2 protein. CONCLUSION: We show for the first time that potential alteration in p53 function in childhood ALL is more common (P = .036) in cases of early treatment failure than in children who remain in long-term continuous remission.

Child↗

Patterns of geographic mobility of persons with AIDS in Canada from time of AIDS index diagnosis to death.

OBJECTIVE: To characterize migration patterns of persons with AIDS in Canada during the period from AIDS diagnosis to death. DESIGN: Descriptive, population-based study. SETTING: Canada. PATIENTS: Canada's AIDS Case Reporting Surveillance System (ACRSS) was linked to deaths in the Canadian Mortality Data Base (CMDB). Probabilistic linkage was based on initials, date of birth, date of death, birthplace, and location at diagnosis and at death. Analysis was restricted to AIDS cases reported from Jan. 1, 1982, to Sept. 30, 1994, and to deaths reported from Jan. 1, 1982, to Dec. 31, 1992. MAIN OUTCOME MEASURES: Change in usual place of residence; migration rates by region and community size. RESULTS: A total of 5755 AIDS cases recorded in the ACRSS were linked to deaths in the CMDB. Of these linked cases, 5366 (93%) included information on province or territory of usual residence or community size. A total of 160 (3.0%) persons with AIDS changed their province or territory of residence between the time of their AIDS diagnosis and death. Multivariate analysis indicated that those who changed residences between AIDS index diagnosis and death were more likely than other persons with AIDS to live in provinces other than British Columbia, Ontario and Quebec (p < 0.001), to be diagnosed earlier (p = 0.004), to be younger (p < 0.001) and to be gay or bisexual (p = 0.042). CONCLUSIONS: Our analysis revealed that only a small proportion of persons changed their residence between AIDS diagnosis and death. Geographic mobility was the greatest among persons with AIDS residing outside of the regions where the overwhelming majority of persons with AIDS in this country reside.

Acquired Immunodeficiency Syndrome↗

Method to assay the concentrations of phenolic constituents of biological interest in wines.

We describe a reversed-phase HPLC method that uses gradient elution and diode array detection to quantitate eight biologically active phenolic constitutions of wine: the cis and trans isomers of resveratrol and their glucosides, catechin, epicatechin, quercetin, and rutin. ODS Hypersil served as the stationary phase; the gradient was formed by acetic acid, methanol and water. Each analysis required an equilibration period of ten minutes and a run time of fourty minutes for completion. Satisfactory peak resolution was achieved following direct injection of a 20-muL sample, and validation was accomplished by on-line spectral comparisons with known standards. Excellent linearity was obtained for all constituents, and the detection limits ranged from 30 mug/L (trans-resveratrol) to 1.5 mg/L (catechin). Recoveries approximated 100% range (95.2-105.5%), and the method provided good precision, with coefficients of variation between 1.17 and 3.38%. All of the phenolics measured were reasonably stable in opened wines protected against sunlight for up to 1 week at room temperature or 4 degrees C, but most showed losses of 10-40% when stored for 6 weeks at either temperature.

Antioxidants↗

High incidence of potential p53 inactivation in poor outcome childhood acute lymphoblastic leukemia at diagnosis.

Previous studies have indicated that p53 gene mutations were an uncommon event in acute lymphoblastic leukemia (ALL) in children. In one series of 330 patients, p53 mutations were seen in fewer than 3%. We analyzed bone marrow mononuclear cells derived from 10 children with ALL at diagnosis who subsequently failed to achieve a complete remission or who developed relapse within 6 months of attaining complete remission for p53 gene mutations and mdm-2 overexpression. We found that three children had p53 gene mutations, and four overexpressed mdm-2. Also, experiments comparing relative levels of mdm-2 RNA and protein in these patients demonstrated that mdm-2 overexpression can occur at the transcriptional and posttranscriptional level in primary leukemic cells. Although we were unable to link Waf-1 RNA expression with p53 status in childhood ALL, our data show potential p53 inactivation by multiple mechanisms in a large percentage of these patients and demonstrate that these alterations can be detected at diagnosis. Inactivation of the p53 pathway may, therefore, be important in children with ALL who fail to respond to treatment and may be useful for the early identification of children requiring alternative therapies.

Adolescent↗

The health of Canada's immigrants in 1994-95.

The "healthy immigrant effect" observed in other countries also prevails in Canada. Immigrants, especially recent immigrants, are less likely than the Canadian-born population to have chronic conditions or disabilities. The effect is most evident among those from non-European countries, who constitute the majority of recent immigrants to Canada. This article compares the health status, health care utilization, and health-related behaviour of immigrants with the Canadian-born population, and is based on self-reported data from the 1994-95 National Population Health Survey. Health status is examined in terms of chronic conditions, disability and health-related dependency. The indicators of health care utilization are hospitalization, contact with physicians and dentists, and unmet needs for health services. The health-related behaviours analysed are smoking and leisure time physical activity.

Adolescent↗

Disability among Canada's aboriginal peoples in 1991.

In 1991, disability rates among adults were high for Aboriginal people, compared with the total Canadian population: 31% versus 13%. For all ages and levels of education, Aboriginal disability rates were much higher than those of Canadians overall. While most younger Aboriginal persons with a disability were only slightly disabled and did not need help with their daily activities, at age 55 and over, more than half of Aboriginal persons with a disability were either moderately or severely disabled and required such help. Nonetheless, most of the Aboriginal population with disabilities who needed help received it, so only a small proportion of them had unmet needs for assistance. The need for assistance, however, increased with the severity of disability. Recent improvements in survivorship mean that more Aboriginal people will live to older ages, at which disability rates are higher. This has implications for their need for health and social services, and the associated costs. Statistics Canada's 1991 Aboriginal Peoples Survey (APS) was used to examine the prevalence and severity of disability and the degree of dependence in the Aboriginal population. Where possible, these results are compared with data for the total Canadian household population from the 1991 Health and Activity Limitation Survey (HALS).

Adolescent↗

Health expectancy by immigrant status, 1986 and 1991.

Analyses based on census data, vital statistics, and data from the Health and Activity Limitation Surveys show that immigrants, especially those from non-European countries, had a longer life expectancy and more years of life free of disability and dependency than did the Canadian-born. But while immigrants were less likely than the Canadian-born to be disabled, they were only slightly less likely to be dependent on others for help with activities of daily living. The reasons for immigrants' longevity and good health are likely related to the "healthy immigrant effect."

Activities of Daily Living↗

Sex ratio of babies is unchanged after transfer of fast- versus slow-cleaving embryos.

PURPOSE: A higher proportion of male offspring has been observed after transferring faster-developing embryos in a number of animal species. Therefore, we evaluated the correlation between the sex ratio of delivered babies and the cleavage stage of transferred embryos in a human IVF-ET program. METHODS: The sex of infants born (n = 104) after transfer of exclusively slower-cleaving < or = 3 cell (n = 41) versus exclusively faster-cleaving > or = 4 cell (n = 63) embryos was compared. Furthermore, all boys and girls resulting from IVF-ET (n = 213) were compared with respect to: the average number of cells in the embryos that were transferred, the embryo with the greatest number of cells in the cohort transferred and the percentage of embryos that were faster cleaving. RESULTS: Thirty seven percent (15/41) of infants resulting from the transfer of exclusively slower-growing embryos were girls and 38% (24/36) of the infants from the faster-growing embryos were girls (NS). The analysis all 213 babies born after 145 embryo transfer procedures did not suggest any differences in embryo cleavage rates in embryo transfers leading to male versus female infants. CONCLUSIONS: A greater number of boys born was not observed after transfer of faster-cleaving embryos as has been described in other animal species. The race to be male may not occur until later cleavage divisions or may not occur in the human embryo.

Cell Division↗

Intravenous albumin does not prevent the development of severe ovarian hyperstimulation syndrome in an in-vitro fertilization programme.

A cohort study was undertaken to compare the effect at the time of oocyte retrieval of the i.v. administration of either 1000 ml of lactated Ringer's solution or 1000 ml of a 5% solution of human albumin on in-vitro fertilization patients at risk for severe ovarian hyperstimulation syndrome (OHSS). A total of 207 patients with an oestradiol concentration > 10,000 pmol/l and/or > 15 follicles (> 10 mm diameter) on the day of human chorionic gonadotrophin (HCG) injection were reviewed. Of these, 158 women received 500 ml of lactated Ringer's solution both before and after egg retrieval, and 49 women received two infusions of 500 ml of 5% human albumin in normal saline at the time of egg retrieval. Severe OHSS developed in two patients who received human albumin and in 10 women who did not receive the albumin. This difference was not statistically significant. There were no differences between the two groups in terms of age, number of follicles punctured at transvaginal oocyte retrieval or oestradiol concentration at the time of HCG injection. The administration of a 5% human albumin solution does not prevent the development of severe OHSS in at risk patients. It does appear to blunt the severity of the condition.

Adult↗

How many stool examinations are necessary to detect pathogenic intestinal protozoa?

Recent reports have suggested that examination of one stool specimen is sufficient to detect protozoa in symptomatic patients. To verify this hypothesis, we examined specimens submitted to the regional laboratory of a large, prepaid health plan that provides primary care to a membership representative of the general population in northern California. We examined the number and results of stool specimen examinations in the two-month period before detection of Entamoeba histolytica in 125 infected persons, of Giardia lamblia in 154 infected persons, and of Dientamoeba fragilis in 60 persons infected with this parasite. About 13% of the entire group had a single stool specimen examined, 19% had two examined, 65% had three examined, and 6% had more than three examined. Most infections were detected in the first specimen or specimens submitted, but many were not detected until later examination. Thirteen patients with E. histolytica (10.4%) required 4-9 examinations. The sensitivity of one examination was compared with that of three examinations; with the additional examinations, the yield increased 22.7% (95% confidence interval [CI] = 11.8-33.5%) for E. histolytica, 11.3% (95% CI = 6.9-81.8%) for G. lamblia, and 31.1% (95% CI = 17.7-54.4%) for D. fragilis. Our results suggest that a single stool specimen examination will miss many pathogenic protozoan infections in symptomatic persons.

Animals↗

The impact of estimation method and population adjustment on Canadian life table estimates.

Abridged life tables centred on 1991 were produced from the 1991 Canadian census, net census undercoverage estimates, and death data from 1990 to 1992. The sensitivity of life table values to differing methods of estimation and population estimates was investigated. The results from four methods by Greville, Chiang, and Keyfitz were compared, and population estimates, both adjusted and unadjusted for net census undercoverage, were used to test the effects of method and type of population estimates on life table values. The results indicate that the method used to derive the estimates had much less influence on the life table values than did the choice of population estimate. The change in life expectancy at birth due to the method of calculation chosen was at most 15 days, whereas the change due to the population estimate chosen was about 73 days. Since there are age, sex and provincial variations in net undercoverage rates, life expectancies differed accordingly.

Adolescent↗

Maternal demographic characteristics and rates of low birth weight in Canada, 1961 to 1990.

Vital statistics on live births were used to examine trends in the demographic characteristics of mothers and rates of low birth weight (LBW) (under 2,500 grams) among children born to residents of Canada (excluding Newfoundland) from 1961 to 1990. The total number of live births with known birth weight declined from 458,000 in 1961 to 397,000 in 1990 (-13%). Over those three decades, the number of LBW infants dropped from 33,100 to 22,000 (-34%), and the proportion of live births accounted for by LBW infants (LBW rate) fell from 7.2% in 1961 to 5.5% in 1990 (-24%). An infant's birth weight is related to the mother's health and socio-economic environment. In urban Canada, the LBW rate was about 1.4 times higher in the lowest income neighbourhoods than in the highest. It was also higher among unmarried mothers than their married counterparts (7.3% vs. 5.0% in 1990), and greater among teenage mothers than those aged 20 to 34 (6.7% vs. 5.4% in 1990). The LBW rate was higher among first-borns than second children (6.0% vs. 4.9% in 1990). From 1961 to 1990, the proportion of births occurring outside marriage rose (especially in Quebec), as did the proportion of mothers of "parity 1" (those giving birth to their first child). Conversely, the proportion of births to teenage mothers declined. The LBW rate generally dropped across all maternal demographic characteristics examined, and in every region, over the period studied. The strongest decline was among unmarried mothers (from 11.3% in 1961 to 7.3% in 1990). By region, Quebec had consistently higher LBW rates than the other three regions. However, Quebec's LBW rate declined dramatically between 1961 and 1990, especially among unmarried mothers (from 13.8% to 7.5%). The LBW rate, standardized to the 1961 distribution of maternal age, parity and marital status, declined from 7.2% in 1961 to 5.1% in 1990 (-29%). By 1990, Quebec's standardized LBW rate (5.2%) was very close to the Canadian average (5.1%), while the Maritimes had the highest standardized LBW rate (5.3%). Thus, after standardization there was an almost complete reversal of the regional ranking which had prevailed in 1961.

Adolescent↗

How far is it to the nearest hospital? Calculating distances using the Statistics Canada Postal Code Conversion File.

This report demonstrates how to calculate distances between points described in terms of latitude and longitude, using the Postal Code Conversion File (PCCF) and other files available from the Geography Division of Statistics Canada. Examples based on hospital data show how the results can be summarized in the form of tables, figures, or maps. Aerial distance to the nearest hospital is a crude but objective indicator of geographic accessibility to hospital services. Distances were calculated between enumeration area centroids for the population and blockface or enumeration area centroids for the hospitals. The median aerial distance to the nearest hospital facility in Canada was less than 3 km, while the mean distance was about 6 km. For teaching hospitals, the median aerial distance was a little less than 30 km, while the mean distance was a little more than 90 km. As most health files for administrative and research purposes contain postal codes, these techniques have potentially wide application.

Abstracting and Indexing↗

Reductions in age-specific mortality among children and seniors in Canada and the United States, 1971-1989.

We compared mortality rates for children and seniors in Canada and the United States in 1971 and 1989. Children in Canada experienced a greater decrease in mortality during this period than did all children in the United States. In particular, while mortality rates for both boys and girls in Canada were higher than those for White children in the United States in 1971, in 1989 the rates for Canadian children were lower. Seniors in Canada experienced a similar or lesser reduction in age-specific mortality than did seniors in the United States. Even though senior women in the United States experienced a reduction in mortality comparable to that of senior women in Canada, Canadian senior women in general had lower level of mortality than their counterparts in the United States. Senior men in the United States experienced a relatively greater reduction than did their counterparts in Canada. The greater decline in mortality for senior men in the United States enabled them to catch up with the lower level of mortality for their Canadian counterparts in 1989. These general conclusions apply whether we compare the Canadian experience to that of the entire population or the White population in the United States. These trends in mortality reductions may reflect the fact that free universal Medicare is available for all ages in Canada, while most publicly-funded Medicare entitlements begin at age 65 in the United States.

Adolescent↗