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M Ricketts

Publications and source records attributed to M Ricketts.

17 recordsLinked to original sources
PubMed2001

A policy analysis of major decisions relating to Creutzfeldt-Jakob disease and the blood supply.

Creutzfeldt-Jakob disease (CJD) is the first major challenge that the blood system has faced since the completion of the Krever inquiry in 1997. We report the results of a detailed policy analysis comparing 2 CJD-related decisions: a 1995 recall of blood from a donor with classic CJD and the 1999 decision to defer donations from individuals with a 6-month travel history to the UK between 1980 and 1996 due to concerns related to variant CJD. Overall, we observed that decision-making improved significantly from 1995 to 1999. In 1998/99 the potential threat of variant CJD was identified at an early stage, and a systematic risk assessment process was initiated. Decision-making was consultative and involved consumers. However, the perception existed that further improvement could take place in the areas of transparency of process and interaction of organizations. We observed that the presence of a second operator had an important impact on decision-making in 1998/99.

Blood Donors↗
PubMed2001

Transfusion-transmitted malaria in Canada.

Three cases of transfusion-transmitted malaria in Canada are described. Although very rare, this diagnosis should be considered in transfusion recipients who have undiagnosed symptoms consistent with malaria. Thick and thin blood smears should be urgently examined to exclude this possibility.

Adult↗
PubMed2001

Emerging infectious disease issues in blood safety.

Improvements in donor screening and testing and viral inactivation of plasma derivatives together have resulted in substantial declines in transfusion-transmitted infections over the last two decades. Most recently, nucleic acid testing techniques have been developed to screen blood and plasma donations for evidence of very recent viral infections that could be missed by conventional serologic tests. Nonetheless, the blood supply remains vulnerable to new and reemerging infections. In recent years, numerous infectious agents found worldwide have been identified as potential threats to the blood supply. Several newly discovered hepatitis viruses and agents of transmissible spongiform encephalopathies present unique challenges in assessing possible risks they may pose to the safety of blood and plasma products.

Blood Donors↗
PubMed2000

CA-Repeat polymorphism in intron 1 of HSD11B2 : effects on gene expression and salt sensitivity.

Mutations in the HSD11B2 gene encoding the kidney (11-HSD2) isozyme of 11beta-hydroxysteroid dehydrogenase cause apparent mineralocorticoid excess, a form of familial hypertension. Because the hypertension associated with AME is of the salt-sensitive type, it seemed possible that decreases in 11-HSD2 activity might be associated with salt sensitivity. To examine this, Italians with mild hypertension underwent a protocol consisting of a rapid intravenous saline infusion and subsequent furosemide diuresis. To determine whether there were genetic associations between HSD11B2 and salt sensitivity, 198 Italians were genotyped for a CA repeat polymorphism (11 alleles) in the first intron. Increased differences in mean arterial pressure between the sodium loaded and depleted states were correlated with shorter CA repeat length (R=0.214, P=0. 0025). The effect behaved as a recessive trait. This suggested that decreased HSD11B2 expression was associated with shorter CA repeat length. Furthermore, activity of renal 11-HSD2 as measured by an increase in the ratio of urinary-free cortisol/urinary-free cortisone was lower in 33 salt-sensitive subjects (urinary-free cortisol/urinary-free cortisone 0.89+/-0.04 [mean+/-SE]) compared with 34 salt-resistant subjects (0.71+/-0.04, P<0.001). However, when minigenes containing either 14 or 23 CA repeats were transfected into rabbit or human kidney cortical collecting duct cells, the construct with 14 repeats was instead expressed at levels 50% higher than those of the construct with 23 repeats, as determined by reverse transcription-polymerase chain reaction. We conclude that polymorphisms in HSD11B2 and decreased 11-HSD2 activity are associated with sensitivity to sodium loading, but a functional explanation for these associations remains to be elucidated.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1998

Notifying patients exposed to blood products associated with Creutzfeldt-Jakob disease: theoretical risk for real people.

BACKGROUND: In July 1995 the Canadian Red Cross Society recalled blood products because of the hypothetical risk of transmission of Creutzfeldt-Jakob disease (CJD) through those blood products. The authors undertook a survey to determine the views of patients and parents of patients about being notified that they or their child had received such blood products. METHODS: The study population consisted of 528 transfusion recipients, of whom 453 (85.8%) were under 16 years of age, notified by the Hospital for Sick Children, Toronto, of the CJD recalls in 1995 and 1996. Families attending an information session were asked to complete a self-administered questionnaire (85 cases). Ninety-seven families randomly selected from those who did not attend the session were interviewed by telephone. The questionnaire was adapted from a questionnaire used to evaluate families' responses to notification of transfusion and risk of HIV infection. RESULTS: More than 80% of the respondents said they wanted to be notified and would want to be notified if there were another recall. On initial receipt of the notification about two-thirds of the respondents had been anxious, fearful or angry. There was no one method of conveying the information that suited all, but a personalized letter was seen as the most acceptable method. INTERPRETATION: Most parents of children who have received blood products are in favour of being informed about the risk of CJD, despite the uncertainty of the information on risk and the anxiety that such information causes.

Adolescent↗
PubMed1997

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↗
PubMed1996

Emerging problems in prion disease.

The authors comment on the report by Drs. Chris MacKnight and Kenneth Rockwood (see pages 529 to 536 of this issue) on the implications for Canadian physicians of human prion diseases. They argue that there is reason for concern about the possible crossover of bovine spongiform encephalopathy to humans in the form of a variant of Creutzfeldt-Jakob disease (CJD) recently identified in the United Kingdom. A second emerging issue is the potential for the causative agent of CJD to be transmitted through donated blood and tissue. Although the epidemiologic evidence suggests that this risk is remote, current national and international initiatives to increase surveillance for new cases of CJD are timely.

Animals↗
PubMed1994

The changing spectrum of AIDS index diseases in Canada.

OBJECTIVE: To describe the changing spectrum of AIDS index diseases in Canada over a 10-year period from 1981 to 1991. DESIGN: A descriptive, population-based study. SETTING: Canada. PATIENTS: All cases of AIDS in Canada reported by the Division of HIV/AIDS Epidemiology of the Department of National Health and Welfare. MAIN OUTCOME MEASURES: Age-standardized rates of initial AIDS manifestations (1987 Centers for Disease Control and Prevention case definition), by year of diagnosis among adults in Canada. RESULTS: A total of 6641 adult AIDS cases were examined. The rate of Pneumocystis carinii pneumonia (PCP) peaked in 1989 with a rate of 3.18 per 100,000, declining to 2.74 per 100,000 in 1991 (P = 0.894). Similarly, the rate of Kaposi's sarcoma (KS) stabilized during this interval from 1.06 per 100,000 in 1987 to 1.14 per 100,000 in 1991 (P = 0.189). In contrast, the rates of all other AIDS-defining illnesses increased from 1.48 per 100,000 in 1987 to 3.43 per 100,000 in 1991 (P = 0.001). For these other AIDS index diseases, significant rate increases were observed for esophageal candidiasis, cytomegalovirus (CMV) diseases, wasting syndrome, toxoplasmosis, and Mycobacterium avium complex (MAC) disease. CONCLUSIONS: Our study shows a leveling and decline in incidence of KS and PCP, respectively, and a concomitant increase of other diagnoses, especially esophageal candidiasis, CMV, wasting syndrome, toxoplasmosis, and MAC disease in Canada. These findings highlight the importance of developing specific strategies to prevent emerging AIDS index diseases and serve as a cautionary note to practicing clinicians, indicating the relative widening of the spectrum of HIV index diseases.

AIDS-Related Opportunistic Infections↗
PubMed1994

Assessment of respiratory limitation in activities of daily life among retired workers.

Epidemiologic studies of occupational lung diseases generally compare symptoms and pulmonary function between groups with differing exposure risks. However, the functional consequences (e.g., on activities of daily life) of statistically significant group differences in either symptoms or pulmonary function are rarely addressed. An understanding of this is important for both the scientific investigators and users of these public health investigations. To address this issue, we developed a 15-item questionnaire to assess breathing-related limitations in activities of daily life, and applied this in a study of 112 retired workers. For each subject, we calculated a limitation score as the number of items associated with breathing difficulty divided by the total number of applicable items. Results from this questionnaire were compared to respiratory symptoms, the Sickness Impact Profile (SIP), lung function test results, 6-min walking distance, and participants' assessment of breathing effort after the walk. The limitation score was significantly higher in subjects reporting dyspnea (22% versus 4%, p < 0.01) or occasional wheeze (27% versus 6%, p < 0.01), and correlated negatively with FEV1, MMEF, and FEV1/FVC (R2 = -0.47, -0.36, and -0.45, respectively, p < 0.0001) and breathing effort after the 6-min walk (R2 = 0.31, p < 0.01). Breathing related limitation in daily activities was also associated with a general health related limitation in household maintenance and ambulation in the SIP (p < 0.01). For each questionnaire item, we compared the responses among subjects with a normal FEV1 to those of subjects with an abnormal FEV1 (below the lower 95% confidence limit).(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗
PubMed1992

Reported seroconversions to human immunodeficiency virus among workers worldwide--a review.

The authors undertook a review of published articles on reported worldwide seroconversions to the human immunodeficiency virus (HIV) among workers who sustained occupational exposure to HIV. Documented seroconversions are occupational exposures for which the worker is tested and found negative for HIV antibody shortly after the exposure (usually within 30 days). The worker may develop symptoms of a retroviral illness, and seroconversion occurs usually within six months. In all cases the worker is interviewed to determine that there were no other risk factors for infection. Review of the literature identified 16 parenteral exposures (needlesticks or cuts with a sharp object), two mucous membrane exposures, two nonintact skin exposures and one cutaneous exposure to infected blood or body fluids.

Aged↗
PubMed1992

How many persons in Canada have been infected with human immunodeficiency virus? An exploration using backcalculation methods.

We have used the technique of backcalculation to estimate the number of persons in Canada who have been infected with human immunodeficiency virus type 1 (HIV) as of July 1989. We first corrected national AIDS surveillance data in Canada for reporting delay and for underreporting. We then used standard Weibull natural history models as well as an alternative progression model in which the hazard of AIDS was dampened in keeping with observed data from large cohorts. Maximum likelihood techniques were then used to derive the infection curve most consistent with these data. Our best estimate based on this alternative progression model, an underreporting rate of 20%, and a logistic infection curve, was that approximately 29,000 persons in Canada had ever had HIV infection as of July 1989. In a sensitivity analysis utilizing less likely assumptions, the estimates ranged from 17,243 to 48,277. Restricting the same backcalculation process to females under the same assumptions, we estimated that approximately 2,900 females in Canada had ever had HIV infection as of July 1989. The best fitting step function infection curve in females appears to be continuing to rise. Given these estimates, it follows that approximately one in ten infected persons in Canada is female. However, females have only accounted for about one in seventeen AIDS cases. These data are in accord with the widespread impression that transmission of HIV to women has occurred more recently and is on the rise across Canada. The current estimate is lower than previous estimates which placed the number of infected Canadians in the 50,000 to 100,000 range. This lowering should not be taken to mean the situation is improving; rather, the early estimates were simply too high having been based on inadequate data and a rudimentary understanding of the natural history of HIV. Backcalculation is an excellent technique for modelling the incidence of HIV infection several years in the past, but it is not reliable for the most recent few years. A significant increase in HIV infection rates may have occurred in the past few years and it would be beyond the capacity of backcalculation to detect. Backcalculation and unlinked cross-sectional specimen surveys together have the potential to provide an effective means of monitoring the HIV epidemic.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Chimeric proteins define variable and essential regions of Ha-ras-encoded protein.

The biological role of amino acid differences between the human 21-kDa Ha-ras protein (p21) and the human 23-kDa R-ras protein (p23) was investigated by engineering mutant Ha-ras p21 molecules containing divergent amino acid sequences from R-ras p23. Variant amino acids from R-ras p23 regions 1-30, 52-57, 67-78, 1-30 and 67-78 together, and 112-124 were substituted for the corresponding Ha-ras p21 amino acid regions 1-4, 26-31, 41-52, 1-4 and 41-52 together, and 86-98, respectively. Rat fibroblasts transfected with genes encoding these position-12 valine-substituted chimeric Ha-ras proteins displayed the same properties of morphological transformation and anchorage-independent growth as Ha-ras T24 oncogene-transformed fibroblasts. However, substitution of variant amino acids from the 80 C-terminal residues (amino acids 138-218) of R-ras p23 for the corresponding p21 amino acids (residues 112-189) inactivated the transforming activity of position-12 valine-substituted p21. The converse substitution of Ha-ras p21 C-terminal residues into R-ras p23 did not result in transformation by position-38 valine-substituted p23. These data are discussed in terms of the structure of ras proteins and the nature of interactions determining the specificity of effector function.

Amino Acid Sequence↗
PubMed1984

Blot hybridisation analysis of genomic DNA.

Restriction endonuclease analysis of specific gene sequences is proving to be a valuable technique for characterisation and diagnosis of inherited disorders. This paper describes detailed protocols for isolation, restriction, and blot hybridisation of genomic DNA. Problems and alternatives in the procedure are discussed and a troubleshooting guide has been provided to help rectify faults.

Autoradiography↗
PubMed1982

Effect of retinol and retinoic acid on permeability, electrical resistance and phase transition of lipid bilayers.

Retinol and retinoic acid have been incorporated into the artificial membrane systems, planar bimolecular lipid membranes and liposomes, and their effects on several membrane parameters have been measured. 1. Retinol and retinoic acid increased the permeability of egg lecithin liposomes to K+, I- and glucose when incorporated into the membranes at levels as low as 0.5 membrane mol%. Retinoic acid influenced permeability more than did retinol for each of the solutes tested. 2. Retinol and retinoic acid both decreased the electrical resistance of egg lecithin-planar bimolecular lipid membranes from 0.5 to 8 membrane mol%. Retinoic acid effected a larger change than did retinol. 3. Retinol and retinoic acid increased the permeability of dimyristoylphosphatidylcholine and dipalmitoylphosphatidylcholine liposomes to water at 1.0 and 3.0 membrane mol%. A larger effect on water permeability was measured for retinoic acid than for retinol. 4. Retinol and retinoic acid at 1.0 and 3.0 membrane mol% were shown to lower the phase-transition temperature of liposomes composed of dimyristoylphosphatidylcholine or dipalmitoylphosphatidylcholine. Phase-transition temperatures were monitored by abrupt changes in water permeability and liposome size associated with the transition. Retinoic acid lowered the phase-transition temperature of dimyristoylphosphatidylcholine liposomes more than did retinol, while both retinoids had almost the same effect on dipalmitoylphosphatidylcholine liposomes.

Dimyristoylphosphatidylcholine↗