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Biomedical subjects

R J Cook

Publications and source records attributed to R J Cook.

At least 19 recordsLinked to original sources
PubMed1999

Two-state mixed renewal processes for chronic disease.

We develop a model based on a two-state mixed renewal process and propose its use for modelling disease activity in studies of chronic conditions. We specify Weibull forms for the conditional transition intensities to allow for time trends, and bivariate frailties to accommodate subject-to-subject variability in the disease process. Extensions of this model are considered for stratified analyses in which strata are defined by the number of past exacerbations. Data from a motivating study of chronic bronchitis are analysed to illustrate the methodology.

Anti-Infective Agents↗
PubMed1999

Monitoring paired binary surgical outcomes using cumulative sum charts.

Correlated binary data are encountered in many areas of medical research, system reliability and quality control. For monitoring failures rates in such situations, simultaneous bivariate cumulative sum (CUSUM) charts with the addition of secondary control limits are proposed. Using an approach based on a Markov chain model, the run length properties of such a monitoring scheme can be determined for sudden, or gradual, changes in the failure rates. The proposed control charts are easy to implement, and are shown to be very effective at detecting small changes in the rate of undesirable outcomes, especially when the changes are gradual. This procedure is illustrated using bivariate outcome data arising from a series of paediatric surgeries. The methodology is sufficiently general that it may be adapted for multivariate normal, binomial or Poisson responses.

Arteries↗
PubMed1999

Human rights and abortion laws.

Human rights protections have developed to resist governmental intrusion in private life and choices. Abortion laws have evolved in legal practice to protect not fetuses as such but state interests, particularly in prenatal life. National and international tribunals are increasingly called upon to resolve conflicts between state enforcement of continuation of pregnancy against women's wishes and women's reproductive choices. Legal recognition that human life begins at conception does not resolve conflicts between respect due to women's reproductive self-determination and due to prenatal life. Human rights protect healthcare providers' claims to conscientious objection, but not at the cost of women's lives and enduring health.

Abortion, Induced↗
PubMed1999

Some ethical and legal issues in assisted reproductive technology.

The potential and actual applications of reproductive technologies have been reviewed by many governmental committees, and laws have been enacted in several countries to accommodate, limit and regulate their use. Regulatory systems have nevertheless left some legal and ethical issues unresolved, and have caused other issues to arise. Issues that regulatory systems leave unresolved, or that systems have created, include disposal of embryos that remain after patients' treatments are concluded, and multiple implantation and pregnancy. This may result in risks to maternal, embryonic and neonatal life and health, and the contentious relief that may be achieved by selective reduction of multiple pregnancies. A further concern arises when clinics must (or choose to) publicize their success rates, and they compete for favorable statistics by questionable patient selection criteria and treatment priorities.

Embryo Disposition↗
PubMed1999

The influence of dietary and nondietary calcium supplementation on blood pressure: an updated metaanalysis of randomized controlled trials.

We updated our previous systematic review of the effect of supplemental calcium on blood pressure. We extended our previous searches on MEDLINE and EMBASE to May 1997 and examined citations from relevant articles. We contacted the authors of eligible trials to ensure the accuracy and completeness of data, and to identify unpublished trials. We included any study in which investigators randomized hypertensive or normotensive people to calcium supplementation or alternative therapy and measured blood pressure for at least 2 weeks. In addition to 32 trials included in the prior metaanalysis, 10 new trials contributed to this metaanalysis. Two pairs of independent reviewers abstracted data and assessed the validity of the study data according to six quality criteria. We calculated the differences in blood pressure change between the calcium supplementation and control groups and pooled the estimates with each trial weighted with the inverse of the variance using a random effects model. The predictors of blood pressure reduction that we examined included method of supplementation, baseline blood pressure, and the methodologic quality of the studies. The pooled analysis shows a reduction in systolic blood pressure of -1.44 mm Hg (95% confidence interval -2.20 to -0.68; P < .001) and in diastolic blood pressure of -0.84 mm Hg (95% confidence interval -1.44 to -0.24; P < .001). We found statistically significant heterogeneity of results across trials (P < or = .02), which persisted when we looked at the nondietary trials alone, but not when we restricted our analysis to dietary trials. Although there was a trend toward larger effects with dietary interventions, none of the possible mediators of blood pressure reduction explained differences in treatment effect. We conclude that calcium supplementation leads to a small reduction in systolic and diastolic blood pressure. The effect of supplemental calcium in the diet is at least as great as nondietary supplementation.

Blood Pressure↗
PubMed1999

International developments in abortion law from 1988 to 1998.

OBJECTIVES: In 2 successive decades since 1967, legal accommodation of abortion has grown in many countries. The objective of this study was to assess whether liberalizing trends have been maintained in the last decade and whether increased protection of women's human rights has influenced legal reform. METHODS: A worldwide review was conducted of legislation and judicial rulings affecting abortion, and legal reforms were measured against governmental commitments made under international human rights treaties and at United Nations conferences. RESULTS: Since 1987, 26 jurisdictions have extended grounds for lawful abortion, and 4 countries have restricted grounds. Additional limits on access to legal abortion services include restrictions on funding of services, mandatory counseling and reflection delay requirements, third-party authorizations, and blockades of abortion clinics. CONCLUSIONS: Progressive liberalization has moved abortion laws from a focus on punishment toward concern with women's health and welfare and with their human rights. However, widespread maternal mortality and morbidity show that reform must be accompanied by accessible abortion services and improved contraceptive care and information.

Abortion, Legal↗
PubMed1999

Validity assessment of the disabilities of arm, shoulder, and hand questionnaire (DASH) for patients with psoriatic arthritis.

OBJECTIVE: To determine whether patients' perception of their functional ability, as measured by the disabilities of arm, shoulder. and hand (DASH) questionnaire, correlates with clinical measures of articular status in patients with psoriatic arthritis (PsA). METHODS: Patients attending the University of Toronto Psoriatic Arthritis Clinic between June and August 1997 were asked to complete a DASH questionnaire during their visits. Clinical assessments were performed according to a standard protocol including number of actively inflamed joints, total number of damaged joints, and grip strength. Spearman rank correlations were used to examine the relationship between clinical measures and the DASH questionnaire. RESULTS: Fifty consecutive patients, 28 men and 22 women, (mean age 49.2 yrs, mean disease duration 13 yrs) were included. DASH scores correlated with clinical measures of upper extremity function including right grip strength (r = -0.47, CI -0.67, -0.21) and number of active joints in the upper limbs (r = 0.65, CI 0.46, 0.79). As expected, the correlation between DASH scores and total number of active joints (r = 0.40, CI 0.14, 0.61) was lower than that between DASH scores and number of active joints in the upper limbs. The DASH was unrelated to clinical damage. CONCLUSION: DASH is a valid instrument for assessing upper extremity function and inflammatory disease activity in patients with PsA.

Arm↗
PubMed1998

Identification of protein-arginine N-methyltransferase as 10-formyltetrahydrofolate dehydrogenase.

S-Adenosylmethionine:protein-arginine N-methyltransferase (EC 2.1.1. 23; protein methylase I) transfers the methyl group of S-adenosyl-L-methionine to an arginine residue of a protein substrate. The homogeneous liver protein methylase I was subjected to tryptic digestion followed by reverse phase high performance liquid chromatography (HPLC) separation and either "on-line" mass spectrometric fragmentation or "off-line" Edman sequencing of selected fractions. Data base searching of both the mass spectrometric and Edman sequencing data from several peptides identified the protein methylase as 10-formyltetrahydrofolate dehydrogenase (EC 1.5.1.6; Cook, R. J., Lloyd, R. S., and Wagner, C. (1991) J. Biol. Chem. 266, 4965-4973; Swiss accession number). This identification was confirmed by comparative HPLC tryptic peptide mapping and affinity chromatography of the methylase on the 5-formyltetrahydrofolate-Sepharose affinity gel used to purify the dehydrogenase. The purified rat liver methylase had approximately 33% of the 10-formyltetrahydrofolate dehydrogenase and 36% of the aldehyde dehydrogenase activity as compared with the recombinant dehydrogenase, which also had protein methylase I activity. Polyclonal antibodies against recombinant dehydrogenase reacted with protein methylase I purified either by polyacrylamide gel electrophoresis or 5-formyltetrahydrofolate affinity chromatography. In each instance there was only a single immunoreactive band at a molecular weight of approximately 106,000. Together, these results confirm the co-identity of protein-arginine methyltransferase and 10-formyltetrahydrofolate dehydrogenase.

Amino Acid Sequence↗
PubMed1998

Incidence of and risk factors for ventilator-associated pneumonia in critically ill patients.

BACKGROUND: Understanding the risk factors for ventilator-associated pneumonia can help to assess prognosis and devise and test preventive strategies. OBJECTIVE: To examine the baseline and time-dependent risk factors for ventilator-associated pneumonia and to determine the conditional probability and cumulative risk over the duration of stay in the intensive care unit. DESIGN: Prospective cohort study. SETTING: 16 intensive care units in Canada. PATIENTS: 1014 mechanically ventilated patients. MEASUREMENTS: Demographic and time-dependent variables reflecting illness severity, ventilation, nutrition, and drug exposure. Pneumonia was classified by using five methods: adjudication committee, bedside clinician's diagnosis, Centers for Disease Control and Prevention definition, Clinical Pulmonary Infection score, and positive culture from bronchoalveolar lavage or protected specimen brush. RESULTS: 177 of 1014 patients (17.5%) developed ventilator-associated pneumonia 9.0 +/- 5.9 days (median, 7 days [interquartile range, 5 to 10 days]) after admission to the intensive care unit. Although the cumulative risk increased over time, the daily hazard rate decreased after day 5 (3.3% at day 5, 2.3% at day 10, and 1.3% at day 15). Independent predictors of ventilator-associated pneumonia in multivariable analysis were a primary admitting diagnosis of burns (risk ratio, 5.09 [95% CI, 1.52 to 17.03]), trauma (risk ratio, 5.00 [CI, 1.91 to 13.11]), central nervous system disease (risk ratio, 3.40 [CI, 1.31 to 8.81]), respiratory disease (risk ratio, 2.79 [CI, 1.04 to 7.51]), cardiac disease (risk ratio, 2.72 [CI, 1.05 to 7.01]), mechanical ventilation in the previous 24 hours (risk ratio, 2.28 [CI, 1.11 to 4.68]), witnessed aspiration (risk ratio, 3.25 [CI, 1.62 to 6.50]), and paralytic agents (risk ratio, 1.57 [CI, 1.03 to 2.39]). Exposure to antibiotics conferred protection (risk ratio, 0.37 [CI, 0.27 to 0.51]). Independent risk factors were the same regardless of the pneumonia definition used. CONCLUSIONS: The daily risk for pneumonia decreases with increasing duration of stay in the intensive care unit. Witnessed aspiration and exposure to paralytic agents are potentially modifiable independent risk factors. Exposure to antibiotics was associated with low rates of early ventilator-associated pneumonia, but this effect attenuates over time.

Adult↗
PubMed1998

A role for jasmonate in pathogen defense of Arabidopsis.

To investigate the role of jasmonate in the defense of plants against fungal pathogens, we have studied a mutant of Arabidopsis, fad3-2 fad7-2 fad8, that cannot accumulate jasmonate. Mutant plants were extremely susceptible to root rot caused by the fungal root pathogen Pythium mastophorum (Drechs.), even though neighboring wild-type plants were largely unaffected by this fungus. Application of exogenous methyl jasmonate substantially protected mutant plants, reducing the incidence of disease to a level close to that of wild-type controls. A similar treatment with methyl jasmonate did not protect the jasmonate-insensitive mutant coi1 from infection, showing that protective action of applied jasmonate against P. mastophorum was mediated by the induction of plant defense mechanisms rather than by a direct antifungal action. Transcripts of three jasmonate-responsive defense genes are induced by Pythium challenge in the wild-type but not in the jasmonate-deficient mutant. Pythium species are ubiquitous in soil and root habitats world-wide, but most (including P. mastophorum) are considered to be minor pathogens. Our results indicate that jasmonate is essential for plant defense against Pythium and, because of the high exposure of plant roots to Pythium inoculum in soil, may well be fundamental to survival of plants in nature. Our results further indicate that the fad3-2 fad7-2 fad8 mutant is an appropriate genetic model for studying the role of this important signaling molecule in pathogen defense.

Journal Article↗
PubMed1998

Toward a successful multinational crop plant genome initiative.

Plant genome research is needed as the foundation for an entirely new level of efficiency and success in the application of genetics and breeding to crop plants and products from crop plants. Genetic improvements in crop plants beyond current capabilities are needed to meet the growing world demand not only for more food, but also a greater diversity of food, higher-quality food, and safer food, produced on less land, while conserving soil, water, and genetic resources. Plant biology research, which is poised for dramatic advances, also depends fundamentally on plant genome research. The current Arabidopsis Genome Project has proved of immediate value to plant biology research, but a much greater effort is needed to ensure the full benefits of plant biology and especially plant genome research to agriculture. International cooperation is critical, both because genome projects are too large for any one country and the information forthcoming is of benefit to the world and not just the countries that do the work. Recent research on grass genomes has revealed that, because of extensive senteny and colinearity within linkage groups that make up the chromosomes, new information on the genome of one grass can be used to understand the genomes and predict the location of genes on chromosomes of the other grasses. Genome research applied to grasses as a group thereby can increase the efficiency and effectiveness of breeding for improvement of each member of this group, which includes wheat, corn, and rice, the world's three most important sources of food.

Animals↗
PubMed1998

von Willebrand disease and its management in oral and maxillofacial surgery.

von Willebrand disease (vWD) is the most common of the hereditary disorders of coagulation. We describe the pathophysiology, diagnosis and the new simplified classification of the disorder and discuss the management of patients about to undergo dental procedures and maxillofacial surgery. Close collaboration between oral and maxillofacial surgeons and haematologists in the management of patients with vWD is essential.

Blood Loss, Surgical↗
PubMed1998

Radiological assessment in psoriatic arthritis.

Our objective was to compare the reliability and responsiveness of the original Steinbrocker's (OS), our modified Steinbrocker's (MS) and Larsen's (L) radiological scoring methods for detecting radiological change in psoriatic arthritis over time. Two sets of radiographs of the hands and feet at least 2 yr apart were selected from 68 patients. Films were randomly presented and scored independently by a rheumatologist (DDG) and a radiologist (DS), in a blinded fashion using all methods. The index of reliability was the intraclass coefficient (ICC) and the responsiveness was assessed using plots and regression analyses. All three radiological scoring methods have excellent interobserver and good intra-observer reliability. L and MS are equally responsive and superior to OS in detecting change in joint damage over time. Thus, the L or MS radiological scoring methods can be used to monitor disease progression in psoriatic arthritis.

Adult↗
PubMed1998

A seven-gene locus for synthesis of phenazine-1-carboxylic acid by Pseudomonas fluorescens 2-79.

Pseudomonas fluorescens 2-79 produces the broad-spectrum antibiotic phenazine-1-carboxylic acid (PCA), which is active against a variety of fungal root pathogens. In this study, seven genes designated phzABCDEFG that are sufficient for synthesis of PCA were localized within a 6.8-kb BglII-XbaI fragment from the phenazine biosynthesis locus of strain 2-79. Polypeptides corresponding to all phz genes were identified by analysis of recombinant plasmids in a T7 promoter/polymerase expression system. Products of the phzC, phzD, and phzE genes have similarities to enzymes of shikimic acid and chorismic acid metabolism and, together with PhzF, are absolutely necessary for PCA production. PhzG is similar to pyridoxamine-5'-phosphate oxidases and probably is a source of cofactor for the PCA-synthesizing enzyme(s). Products of the phzA and phzB genes are highly homologous to each other and may be involved in stabilization of a putative PCA-synthesizing multienzyme complex. Two new genes, phzX and phzY, that are homologous to phzA and phzB, respectively, were cloned and sequenced from P. aureofaciens 30-84, which produces PCA, 2-hydroxyphenazine-1-carboxylic acid, and 2-hydroxyphenazine. Based on functional analysis of the phz genes from strains 2-79 and 30-84, we postulate that different species of fluorescent pseudomonads have similar genetic systems that confer the ability to synthesize PCA.

Amino Acid Sequence↗
PubMed1998

HLA markers and progression in psoriatic arthritis.

OBJECTIVE: To investigate whether the addition of all serologically defined HLA antigens to a baseline model further influences the predisposition to disease progression in psoriatic arthritis (PsA). METHODS: Patients with PsA followed prospectively over 19 years were studied. Clinical and laboratory assessments of both active inflammation and clinical damage were performed at 6 month intervals according to a standard protocol. Progression of damage was defined as transition to higher damage states defined by the number of damaged joints. A model that provides estimates of the ratio of transition rates for an individual with the antigen versus one without, and examines the antigen effect on each of the 3 transition rates, was used. HLA antigens were examined in groups by loci under the assumption of common effects across transitions when added to the basic model. The significance levels were examined in comparison with Bonferroni type corrections. Likelihood ratio chi-squared statistics were used as a basis for the significance levels. In total, 292 patients with PsA were included in the study. RESULTS: Only HLA-B22 was added to the original model, which includes HLA-B39, providing risk for progression in early stages, HLA-B27 in the presence of HLA-DR7 providing risk for progression through all states, and DQw3 providing increased risk in the absence of DR7, while in the presence of DR7 it provides "protection." HLA-B22 provides protection from disease progression through all states. CONCLUSION: This study extends our report that HLA antigens serve as markers for disease progression in PsA.

Adolescent↗