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M Johnston

Publications and source records attributed to M Johnston.

At least 55 records · Page 3Linked to original sources
PubMed2001

COMPASS: a complex of proteins associated with a trithorax-related SET domain protein.

The trithorax genes encode an evolutionarily conserved family of proteins that function to maintain specific patterns of gene expression throughout cellular development. Members of this protein family contain a highly conserved 130- to 140-amino acid motif termed the SET domain. We report the purification and molecular identification of the subunits of a protein complex in the yeast Saccharomyces cerevisiae that includes the trithorax-related protein Set1. This protein complex, which we have named COMPASS (Complex Proteins Associated with Set1), consists of seven polypeptides ranging from 130 to 25 kDa. The same seven proteins were identified in COMPASS purified either by conventional biochemical chromatography or tandem-affinity tagging of the individual subunits of the complex. Null mutants missing any one of the six nonessential subunits of COMPASS grow more slowly than wild-type cells under normal conditions and demonstrate growth sensitivity to hydroxyurea. Furthermore, gene expression profiles of strains missing either of two nonessential subunits of COMPASS are altered in similar ways, suggesting these proteins have similar roles in gene expression in vivo. Molecular characterization of trithorax complexes will facilitate defining the role of this class of proteins in the regulation of gene expression and how their misregulation results in the development of human cancer.

Chromatography, Liquid↗
PubMed2001

Baseline staging tests in primary breast cancer: a practice guideline.

BACKGROUND: Breast cancer develops in over 7000 women each year in Ontario. These patients will all undergo some staging work-up at diagnosis. The Breast Cancer Disease Site Group of the Cancer Care Ontario Practice Guidelines Initiative reviewed the evidence and indications for routine bone scanning, liver ultrasonography and chest radiography in asymptomatic women who have undergone surgery for breast cancer. METHODS: A systematic review of the published literature was combined with a consensus interpretation of the evidence in the context of conventional practice. RESULTS: There were 11 studies of bone scanning reported between 1972 and 1980, involving a total of 1307 women; bone scans detected skeletal metastases in 6.8% of those with stage I breast cancer, 8.8% with stage II and 24.5% with stage III. A total of 5407 women participated in 9 studies of bone scanning reported between 1985 and 1995; in these studies, bone scans detected skeletal metastases in only 0.5% of women with stage I disease, 2.4% with stage II and 8.3% with stage III. Among 1625 women in 4 studies of liver ultrasonography reported between 1988 and 1993, hepatic metastases were detected in 0% of patients with stage I disease, 0.4% with stage II and 2.0% with stage III. Among 3884 patients in 2 studies of chest radiography published in 1988 and 1991, lung metastases were detected in 0.1% of those with stage I, 0.2% with stage II and 1.7% with stage III. False-positive rates ranged from 10% to 22% for bone scanning, 33% to 66% for liver ultrasonography and 0% to 23% for chest radiography. The false-negative rate for bone scanning was about 10%. RECOMMENDATIONS: The following recommendations apply to women with newly diagnosed breast cancer who have undergone surgical resection and who have no symptoms, physical signs or biochemical evidence of metastases. Routine bone scanning, liver ultrasonography and chest radiography are not indicated before surgery. In women with intraductal and pathological stage I tumours, routine bone scanning, liver ultrasonography and chest radiography are not indicated as part of baseline staging. In women who have pathological stage II tumours, a postoperative bone scan is recommended as part of baseline staging. Routine liver ultrasonography and chest radiography are not indicated in this group but could be considered for patients with 4 or more positive lymph nodes. In women with pathological stage III tumours, bone scanning, liver ultrasonography and chest radiography are recommended postoperatively as part of baseline staging. In women for whom treatment options are restricted to tamoxifen or hormone therapy, or for whom no further treatment is indicated because of age or other factors, routine bone scanning, liver ultrasonography and chest radiography are not indicated as part of baseline staging.

Bone Neoplasms↗
PubMed2001

Systematic overview of the evidence for brachytherapy in clinically localized prostate cancer.

BACKGROUND: Brachytherapy (permanent implantation of radioactive seeds) has emerged as an alternative to existing standard therapy with radical prostatectomy or external beam radiotherapy in the treatment of clinically localized (T1 and T2) prostate cancer. The Genitourinary Cancer Disease Site Group of the Cancer Care Ontario Practice Guidelines Initiative examined the role of brachytherapy in treating clinically localized prostate cancer. METHODS: A systematic review of articles published from 1988 to April 1999, retrieved through a search of MEDLINE and CANCERLIT databases, was combined with a consensus interpretation of the evidence in the context of conventional practice. RESULTS: Although there were no randomized trials comparing brachytherapy with standard treatment, evidence was available from 13 case series and 3 cohort studies. Rates of freedom from biochemical failure (biochemically no evidence of disease [bNED]) varied considerably from one series to another and were highly dependent on tumour stage, grade and pretreatment serum prostate-specific antigen (PSA) levels. Results in patients with favourable tumours (T1 or T2 tumour, Gleason score of 6 or lower, serum PSA level of 10 ng/mL [microgram/L] or less) were comparable to those in patients undergoing radical prostatectomy. Acute urinary retention was reported in 1%-14% of patients. Long-term sequelae occurred in less than 5% of patients and included urinary incontinence, cystitis, urethral strictures and proctitis. Sexual potency was maintained after implantation in 86%-96% of patients. INTERPRETATION: At present, there is insufficient evidence to recommend the use of brachytherapy over current standard therapy for localized prostate cancer. Brachytherapy using transrectal ultrasound guidance for seed implantation is promising in terms of freedom from biochemical failure in selected patients with early-stage prostate cancer. Brachytherapy is currently available outside of clinical trials, but whenever possible patients should be asked to participate in randomized trials comparing brachytherapy and current standard therapy. Brachytherapy should be available to selected patients (those with T1c or T2a tumours, a Gleason score of 6 or lower and a serum PSA level of 10 micrograms/L or less), after discussion of the available data and potential adverse effects.

Brachytherapy↗
PubMed2001

Use of a fixed activated partial thromboplastin time ratio to establish a therapeutic range for unfractionated heparin.

BACKGROUND: The commonly recommended therapeutic range for patients receiving unfractionated heparin of 1.5 to 2.5 times the control activated partial thromboplastin time (aPTT) is not universally applicable. It has been suggested that the therapeutic range for each aPTT reagent should be based on plasma heparin levels. We sought to identify an aPTT ratio that corresponds to therapeutic anti--factor Xa heparin levels for combinations of several reagents and coagulometers that are commonly used. METHODS: Citrated plasma was collected from 126 unselected patients receiving unfractionated heparin. Four automated coagulometers and 6 commercial aPTT reagents were used to measure the aPTT. Plasma anti--factor Xa levels were measured by means of a commercially available assay. The relationship between the aPTT results and anti-factor Xa heparin levels for each reagent-coagulometer combination was determined by linear regression analysis, and the aPTT results corresponding to therapeutic anti--factor Xa heparin levels were calculated. RESULTS: For all reagent-coagulometer combinations studied, an aPTT ratio of 1.5 resulted in anti--factor Xa heparin levels considerably below the lower limit of the therapeutic range. When the aPTT was performed on any of the coagulometers assessed with the use of Actin (Dade Diagnostics, Aguada, Puerto Rico) and IL Test (Instrumentation Laboratories, Fisher Scientific, Unionville, Ontario) reagents, aPTT ratios necessary to achieve therapeutic anti--factor Xa heparin levels approximated 2.0 to 3.5. CONCLUSION: For laboratories that cannot perform heparin levels, the use of less responsive reagents and any of the coagulometers studied, along with target aPTT ratio between 2.0 and 3.5, appears to be a reasonable alternative.

Antithrombin III↗
PubMed2001

A latex D-dimer reliably excludes venous thromboembolism.

BACKGROUND: D-Dimer, a cross-linked fibrin degradation product, has a high sensitivity in patients with suspected venous thrombosis. Traditional latex D-dimer assays, however, have not been sufficiently sensitive to exclude venous thromboembolism. METHODS: To determine the clinical utility of a latex D-dimer assay (MDA D-Dimer; Organon Teknika Corporation, Durham, NC) in patients with suspected venous thromboembolism, we conducted a retrospective cohort study involving 595 unselected patients at 4 tertiary care hospitals. Patients had blood drawn for performance of the D-dimer assay and underwent objective testing for venous thromboembolism. Pretest probability was determined using validated models in 571 patients. Patients were classified as venous thromboembolism positive or negative according to results of objective tests and 3-month follow-up. The sensitivities, specificities, predictive values, and negative likelihood ratios of the assay were calculated for all patients and for subgroups of patients with known cancer or a low, moderate, or high pretest probability of venous thromboembolism. RESULTS: The prevalence of venous thromboembolism was 19.0% (113/595). Of those who had a pretest probability assessment, 35.9% had a low pretest probability, 49.7% a moderate pretest probability, and 14.4% a high pretest probability. Using a discriminant value of 0.50 microg fibrinogen equivalent units per milliliter, the assay showed an overall sensitivity of 96%, a negative predictive value of 98%, a specificity of 45%, and a negative likelihood ratio of 0.09. In patients with a low or moderate pretest probability, the sensitivity, negative predictive value, and negative likelihood ratio were 97%, 99%, and 0.07, respectively. CONCLUSIONS: The MDA D-Dimer assay is the first latex agglutination assay with sufficient sensitivity to be clinically useful in the exclusion of venous thromboembolism. A negative result has the potential to be used as the sole test to exclude venous thromboembolism in patients with a low or moderate pretest probability of disease.

Female↗
PubMed2001

Community-based cancer screening for underserved women: design and baseline findings from the Breast and Cervical Cancer Intervention Study.

BACKGROUND: Underutilization of breast and cervical cancer screening has been observed in many ethnic groups and underserved populations. Effective community-based interventions are needed to eliminate disparities in screening rates and thus to improve prospects for survival. METHODS: The Breast and Cervical Cancer Intervention Study was a controlled trial of three interventions in the San Francisco Bay Area from 1993 to 1996: (1) community-based lay health worker outreach; (2) clinic-based provider training and reminder system; and (3) patient navigator for follow-up of abnormal screening results. Study design and a description of the interventions are reported along with baseline results of a household survey conducted in four languages among 1599 women, aged 40-75. RESULTS: Seventy-six percent of women ages 40 and over had had at least one mammogram, and most had had a clinical breast examination (88%) and Pap smear (89%). Rates were significantly lower for non-English-speaking Latinas and Chinese women (56 and 32%, respectively, for mammography), and maintenance screening (three mammograms in the past 5 years) varied from 7% (non-English-speaking Chinese) to 53% (Blacks). Pap smear screening in the past 3 years was low among non-English-speaking Latinas (72%) and markedly lower among non-English-speaking Chinese women (24%). The strongest predictors of screening behavior were having private health insurance and frequent use of medical services. Having a regular clinic and speaking English were also important. Race/ethnicity, education, household income, and employment status were, overall, not significant predictors of screening behavior. CONCLUSIONS: These baseline results support the importance of cancer screening interventions targeted to persons of foreign origin, particularly those less acculturated.

Adult↗
PubMed2001

Problems with the sickness impact profile: a theoretically based analysis and a proposal for a new method of implementation and scoring.

The Sickness Impact Profile (SIP) is one of the most widely used health status measures, but there are problems with the measure that lead to inconsistent and illogical scores. There are many desirable features to the SIP development methodology in that it is based on a good range of items and the item weightings are valuable. The current method of scoring the SIP is the use of a summated total and was selected based on limited empirical evidence. However, in this paper we argue that there are problems with the SIP because the current empirically derived method of scoring is incompatible with both the underlying theoretical scaling framework (Thurstone scaling) and the nature of the items in the SIP. In addition, the items do not have properties consistent with the scaling methodology. We suggest that it is crucial to take both a theoretical and empirical approach to selecting a scoring method. To examine problems associated with the SIP we explored the underlying scaling methodology and identified the types of items in the SIP. A new method of scoring is proposed that is consistent with the items and scaling in the SIP, namely using the maximum individual weighting from the items that were checked as a category score. This new method of scoring resolves many of the previously observed problems in the SIP. The new method of scoring also presented the opportunity for a new implementation of the SIP that reduces the number of items that most respondents, especially those with severe limitations, would be asked. Without taking a theoretical approach to scoring we suggest that subsequent, empirically based, scale amendments are unlikely to solve the problems. It is proposed that this new method of scoring justifies a thorough empirical investigation.

Activities of Daily Living↗
PubMed2001

Consequences of disease: testing the WHO International Classification of Impairments, Disabilities and Handicaps (ICIDH) model.

The International Classification of Impairments, Disabilities and Handicaps (ICIDH) model proposes that there are three consequences of disease, impairment (I), disability (D) and handicap (H) and that they are sequentially related. This paper examines first, whether I, D and H can be measured independently and second, whether there is support for the sequential or causal relationship between the three constructs. Cross-sectional data from a representative sample of 101 disabled adults and longitudinal data from 108 myocardial infarction (MI) and 68 Stroke patients were used. Standard measures of I were used for each clinical condition. Measures of D and H were derived from the British version of the Sickness Impact Profile (SIP) and additional measures of D were available for the Stroke group. Judges classified SIP items according to ICIDH definitions of D and H. Correlation, Confirmatory Factor Analyses and Path Analyses were used to examine the main hypotheses. Valid measures of D and H were derived and there was evidence of separation of the three constructs for the Stroke patients but not for the other groups. For both Stroke and MI, I was not predictive of D and H. For Stroke, the best path model included a path from D to H, but not from H to D and this was found for self-report and performance measures of D. Using these measures, the ICIDH model was supported in that D predicted H for stroke, but there was no support for a path between I and D or between I and H. Further it was not always possible to distinguish the three constructs. Possible limitations in the measures and in the ICIDH model as a testable scientific model are discussed.

Activities of Daily Living↗
PubMed2001

Sources of support and the physical and mental well-being of young women with breast cancer.

Women following the stress resulting from the diagnosis and treatment for breast cancer draw resources from their network of friends and relatives. These resources include both emotional support and instrumental resources such as getting a ride to a medical appointment. Emotional support buffers the effects of the stresses they face and improves their mental well-being while the existence, rather than the use, of instrumental supports is positively related to physical well-being. These hypotheses are tested on a population-based cohort of 336 women in the United States, diagnosed and treated for breast cancer when aged 50 or less. Most are married (65%), work (75%), have dependent children (63%), are white (70%), and had a mastectomy (51%). Results of the multi-variate analyses indicate that consistent with predictions, controlling for socio-demographic and treatment-related variables, the size of the social network was related to greater emotional and instrumental support, and greater emotional support was related to better mental well-being. Contrary to predictions, greater use of instrumental resources was related to poorer physical well-being. The results indicate the importance of social resources on well-being following life-threatening illness.

Adaptation, Psychological↗
PubMed2001

Surveying Saccharomyces genomes to identify functional elements by comparative DNA sequence analysis.

Comparative sequence analysis has facilitated the discovery of protein coding genes and important functional sequences within proteins, but has been less useful for identifying functional sequence elements in nonprotein-coding DNA because the relatively rapid rate of change of nonprotein-coding sequences and the relative simplicity of non-coding regulatory sequence elements necessitates the comparison of sequences of relatively closely related species. We tested the use of comparative DNA sequence analysis to aid identification of promoter regulatory elements, nonprotein-coding RNA genes, and small protein-coding genes by surveying random DNA sequences of several Saccharomyces yeast species, with the goal of learning which species are best suited for comparisons with S. cerevisiae. We also determined the DNA sequence of a few specific promoters and RNA genes of several Saccharomyces species to determine the degree of conservation of known functional elements within the genome. Our results lead us to conclude that comparative DNA sequence analysis will enable identification of functionally conserved elements within the yeast genome, and suggest a path for obtaining this information.

Base Sequence↗
PubMed2001

Intracranial pressure accommodation is impaired by blocking pathways leading to extracranial lymphatics.

Tracer studies indicate that cerebrospinal fluid (CSF) transport can occur through the cribriform plate into the nasal submucosa, where it is absorbed by cervical lymphatics. We tested the hypothesis that sealing the cribriform plate extracranially would impair the ability of the CSF pressure-regulating systems to compensate for volume infusions. Sheep were challenged with constant flow or constant pressure infusions of artificial CSF into the CSF compartment before and after the nasal mucosal side of the cribriform plate was sealed. With both infusion protocols, the intracranial pressure (ICP) vs. flow rate relationships were shifted significantly to the left when the cribriform plate was blocked. This indicated that obstruction of the cribriform plate reduced CSF clearance. Sham surgical procedures had no significant effects. Estimates of the proportional flow through cribriform and noncribriform routes suggested that cranial CSF absorption occurred primarily through the cribriform plate at low ICPs. Additional drainage sites (arachnoid villi or other lymphatic pathways) appeared to be recruited only when intracranial pressures were elevated. These data challenge the conventional view that CSF is absorbed principally via arachnoid villi and provide further support for the existence of several anatomically distinct cranial CSF transport pathways.

Animals↗
PubMed2001

Comparison of cerebrospinal fluid transport in fetal and adult sheep.

We quantified cerebrospinal fluid (CSF) transport (conductance) and CSF outflow resistance in late-gestation fetal and adult sheep using two methods, a constant pressure infusion method and a bolus injection technique into the lateral ventricles. No significant differences in CSF conductance (fetus 0.013 +/- 0.002, adult 0.014 +/- 0.003 ml x min(-1) x cm H(2)O(-1)) or CSF outflow resistance (fetus 83.7 +/- 9.8, adult 84.7 +/- 19.7 cm H(2)O x ml(-1) x min) were observed. To confirm CSF transport to plasma in fetal animals, (125)I- or (131)I-labeled human serum albumin (HSA) was injected into the lateral ventricles. The tracer entered fetal plasma with an average mass transport rate of 1.91 +/- 0.47% injected/h (n = 9). In two fetuses, we monitored the tracer appearance in plasma and cervical and thoracic duct lymph after injection of radioactive HSA into the ventricular CSF. As was the case in adult animals, fetal tracer concentrations increased in all three compartments over time, with the highest concentrations measured in lymph collected from the cervical lymphatics. These results 1) indicate that global CSF transport parameters in the late-gestation fetus and adult sheep are similar and 2) suggest an important role for extracranial lymphatic vessels in CSF transport before birth.

Animals↗
PubMed2001

Self-efficacy and goal importance in the prediction of physical disability in people following hospitalization: a prospective study.

OBJECTIVES: This prospective study evaluates the role of self-efficacy and goal importance in predicting decreases in disability in activities of everyday living. METHOD: Disability, self-efficacy and goal importance were each assessed before and at 3 and 9 months after participants underwent joint replacement surgery. RESULTS: Disability had decreased at 3 and 9 months post-surgery assessments. Self-efficacy beliefs were higher at 3 and 9 months following surgery while goal importance was increased at 9 months but not at 3 months. Medical variables and prior disability predicted disability at 3 months. Social-cognitive variables did not contribute to the prediction of 3 months disability. Pre-surgery goal importance and self-efficacy at 3 months were independent predictors of disability at 9 months after controlling for pre-surgery and 3 months disability. Evidence also suggested that goal importance and self-efficacy interacted to predict levels of disability at 9 months following surgery. CONCLUSIONS: The findings demonstrate that recovery is governed not solely by medical phenomena but also by psychological variables and suggest that modification of these variables may have an impact on recovery outcomes. Moreover, attention should be paid to the timing of such intervention and to the length of follow-up.

Journal Article↗
PubMed2001

Spontaneous, elicited and cued causal attributions in the year following a first myocardial infarction.

OBJECTIVES: To assess myocardial infarction (MI) patients' causal beliefs, how they change over time and the effects of different assessment methods. METHOD: The study used a longitudinal design with a follow-up to 1 year. The participants were 100 MI patients who were recruited within 72 hours of admission. Each participant was interviewed and their causal attributions (spontaneous, elicited and cued) were assessed using four different methods. RESULTS: 'Stress', 'smoking', 'it is in the family', 'eating fatty foods' and 'work' items were the most commonly mentioned causes for the MI at all times of measurement and across all measures. On each occasion 'stress' and 'smoking' were selected as the most important causes and patients made fewer attributions over time. Finally, the attributional assessment method used did not affect type of attributions but fewer attributions were reported using the spontaneous method. CONCLUSION: Patients do provide causal attributions following an MI. While many are similar to causal factors identified by medicine, patients appear to place more emphasis on 'stress'. As predicted by attribution theory, attributions changed over time. The method of obtaining the attributions does not appear to affect the attributions made but greatly affects their number. While all the methods used have their place, the cued method with a list of possible attributions offers a rich return for effort expended.

Journal Article↗
PubMed2001

Surveillance programs for early stage non-seminomatous testicular cancer: a practice guideline.

BACKGROUND AND PURPOSE: To identify an appropriate surveillance program for men with clinical stage I non-seminomatous germ cell tumors of the testis (NSGCT). MATERIALS AND METHODS: A systematic review of the published literature was combined with a consensus process, around the interpretation of the evidence in the context of conventional practice, to develop an evidence-based practice guideline. RESULTS: No randomized controlled trials (RCTs) comparing surveillance schedules were found, but data from 12 case series and one RCT which compared radiotherapy with surveillance were reviewed. Variations in the schedules were not associated with observed variations in relapse, salvage, or survival rates. CONCLUSIONS: Men with clinical stage I testicular cancer, as defined by a normal physical examination, normal radiological scans (computed tomography [CT]) and serum markers (alpha-fetoprotein [AFP] and beta-subunit of human chorionic gonadotropin (betaHCG) which are normal or fall within normal limits during their expected half-lives, are eligible for surveillance. A recommended surveillance schedule is as follows: 1) Physical examination, blood serum marker tests (AFP and HCG), and chest x-rays should be conducted every month in the first year, every 2 months in the second year, every 3 months in the third year, and every 6 months in the fourth and fifth years; and 2) CT scans of the abdomen and pelvis should be conducted every 3 months in the first year, every 4 to 6 months in the second year and every 6 months in the third year, and once a year in the fourth and fifth year.

Germinoma↗
PubMed2001

Fibrinolytic variables in patients with recurrent venous thrombosis: a prospective cohort study.

To determine whether fibrinolytic testing predicts recurrent venous thrombosis, we have performed a prospective cohort study in which 303 patients with a first episode of venous thromboembolism underwent comprehensive fibrinolytic testing while receiving oral anticoagulants, and after anticoagulants had been discontinued. They were then followed for up to 3 years for recurrent venous thrombosis. No systematic differences in the levels or activity of type 1 plasminogen activator inhibitor (PAI-1), tissue plasminogen activator (tPA) or euglobulin clot lysis times were detected between patients who did, or did not, suffer recurrent thrombosis. There were also no differences in these variables when patients whose initial thrombosis was idiopathic were compared to patients whose thrombosis occurred in the setting of a known thrombotic risk factor. Based on these results, neither measuring fibrinolytic parameters in patients with venous thromboembolism, nor modification of treatment based on the results of such testing, are justified. Our study also confirms that patients with idiopathic venous thromboembolism have a high risk of recurrence.

Anticoagulants↗