PubMed Health⌕ Search

Biomedical subjects

R Cook

Publications and source records attributed to R Cook.

At least 37 records · Page 2Linked to original sources
PubMed2001

Phase II study of thalidomide in the treatment of recurrent glioblastoma multiforme.

Treatment options and prognosis remains poor for patients with recurrent glioblastoma multiforme. These tumors are highly vascularised and over express angiogenic factors such as vascular endothelial growth factor and may potentially be responsive to antiangiogenic therapies. We present the results of a phase II trial of Thalidomide, an antiangiogenic agent, in the treatment of recurrent glioblastoma multiforme. Patients were treated with 100 mg/day of Thalidomide, increased at weekly intervals by 100 mg to a maximum tolerated dose of 500 mg/d. Forty-two patients were enrolled, with 38 patients being assessable for response and 39 for toxicity. Two patients (5%) achieved a partial response and 16 (42%) had stable disease. The median survival was 31 weeks and the 1-year survival was 35%. Patients who had a partial response or stable disease had either a stabilisation or improvement in quality of life scores or performance status. Overall Thalidomide was well tolerated with no grade 4 toxicities and no treatment related deaths. The median maximum tolerated dose was 300 mg/day. The most common toxicity was fatigue to which patients developed tachyphylaxis. There was no correlation demonstrated with plasma vascular endothelial growth factor levels and response or survival. Thalidomide is a well-tolerated drug that may have some activity in the treatment of recurrent glioblastoma. Optimum dosing with antiangiogenic agents is currently under investigation. Chronic low dose therapy may be required to see conventional responses or improvements in time to progression. The dose required to achieve optimal biological impact may be better defined once we have established reliable surrogate endpoints.

Adult↗
PubMed2001

Multiple organ dysfunction: baseline and serial component scores.

OBJECTIVE: The multiple organ dysfunction score (MODS) describes and quantifies organ-specific physiology. The objective of this study was to examine the relation between six components of MODS (cardiovascular, respiratory, renal, central nervous system, hepatic, and hematologic) measured at admission to the intensive care unit (ICU) and during the ICU stay, with time to death in the ICU. DESIGN: Prospective observational cohort study. SETTING: Sixteen Canadian ICUs. PATIENTS: A total of 1,200 patients were mechanically ventilated for >48 hrs. MEASUREMENTS AND MAIN RESULTS: The six organ systems comprising MODS were measured at ICU admission (baseline scores) and daily thereafter. The change in organ dysfunction each day (serial scores) were calculated as daily component scores minus the corresponding baseline component scores. In Cox regression analyses, the independent explanatory variables were the MODS components measured at baseline and serially, and the dependent variable was the time from admission to ICU mortality. When each organ system was analyzed individually, both the baseline and serial MODS for the cardiovascular, respiratory, renal, central nervous system, and hematologic components were significantly associated with ICU mortality. After adjusting for the serial hepatic score, the baseline hepatic score was unrelated to mortality. After adjusting for all baseline and serial MODS components in aggregate, four organ systems were significantly associated with ICU mortality: cardiovascular (baseline relative risk [RR], 1.5; serial RR, 1.4); respiratory (baseline RR, 1.4; serial RR, 1.4); renal (baseline RR, 1.3; serial RR, 1.5); and central nervous system (baseline RR, 1.6; serial RR, 1.7). We found that the relative risk of mortality related to organ dysfunction varied significantly over time and among organ systems. Baseline respiratory function was not associated with mortality until the second ICU week (week 1: RR, 1.1 [0.9-1.4]; week 2 onward: RR, 1.9 [1.5-2.4]); the same was true for the change in respiratory function as measured by the serial respiratory score (week 1: RR, 1.2 [1.0-1.5]; week 2 onward: RR, 1.7 [1.4-2.1]). The serial hepatic score was not associated with mortality until the fourth ICU week (weeks 1-3: RR, 0.9 [0.7-1.1]; week 4 onward: RR, 1.4 [1.0-2.0]). CONCLUSIONS: Organ dysfunction scores describe physiology at ICU admission and during ICU stay. Although patterns vary by system, daily MODS component scores provide additional prognostic value over baseline MODS.

APACHE↗
PubMed2001

A meta-analysis of mammography screening promotion.

The purpose of this study was to identify factors that influence the effectiveness of interventions in increasing women's use of mammography screening programs. To this end, we conducted a systematic literature review of studies published between 1966 and 1997. In this review, we recorded data about the year and country in which studies were completed, the study design, the methods for measuring screening rates, various sample characteristics, the nature of the intervention, and the resulting screening rates. The PRECEDE model was used as a framework to make distinctions between the various interventions. To synthesize evidence about the baseline screening rates and the effect of interventions on the incidence of mammography screening, we fit random-effects logistic regression models. These models revealed that more recent studies (those conducted from 1990 to 1996) were associated with higher screening rates (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.2-3.9). Conversely, those designed to target older women (minimum age, 50-65 years) and those set in clinics exhibited smaller screening rates (OR, 0.6, 95% CI, 0.3-1.0, and OR, 0.5; 95% CI, 0.3-0.8, respectively). The meta-analyses also suggested methodologic issues that must be considered before the relative strength of various interventions can be assessed rigorously.

Adult↗
PubMed2000

Recognizing adolescents' 'evolving capacities' to exercise choice in reproductive healthcare.

All countries (except Somalia and the USA) have adopted the UN Convention on the Rights of the Child, which usually applies to individuals aged under 18 years. The Convention requires governments to 'respect the responsibilities, rights and duties of parents [or others acting as parents] ellipsis in a manner consistent with the evolving capacities of the child'. Many adolescents gain capacity to make decisions for themselves concerning reproductive and sexual health services, and to decide issues of confidentiality. Immature adolescents must be given usual protections. The Convention sets a legal limit on parental power to deny capable adolescents reproductive and sexual health services. The question whether an adolescent is a 'mature minor' must be decided by health service providers independently of parental judgment. The specific duties of government and health service providers to implement adolescent rights regarding their reproductive and sexual health needs are examined.

Adolescent↗
PubMed2000

Complementary medicine: knowledge, use and attitudes of doctors.

The recent growth in interest in the use of complementary medicine by the general public has been well reported. Health professionals, particularly nurses and midwives, are incorporating the use of complementary therapies into their practice. The medical profession is involved in the political processes affecting legislation governing complementary medicine and it is therefore important to determine the views of doctors when considering the use of complementary therapies by nurses within the health-care system. A critical review of published research studies which consider the knowledge, use and attitudes of doctors to complementary medicine is presented. These studies suggest doctors' interest in complementary medicine but they also raise a number of concerns including lack of evidence to demonstrate effectiveness, possible harmful effects, inadequate knowledge of doctors and lack of statutory regulation for most therapies. Recommendations of recent reports are outlined which attempt to address these and other issues.

Attitude of Health Personnel↗
PubMed2000

A national survey: transporting patients within Australian hospitals.

A telephone survey was conducted to describe current practices and policies of patient transport in Australian hospitals. The survey had a 94% response rate. Results showed considerable variability and ambiguity throughout the sample in both practice and policy. Findings also indicated that criteria used for transport practices were predominantly shaped by physiological and technological considerations. Factors related to human and financial resources, as well as psychological and emotional aspects of the patient's condition, received little attention.

Australia↗
PubMed2000

Effects of stress reduction on carotid atherosclerosis in hypertensive African Americans.

BACKGROUND AND PURPOSE: African Americans suffer disproportionately higher cardiovascular disease mortality rates than do whites. Psychosocial stress influences the development and progression of atherosclerosis. Carotid intima-media thickness (IMT) is a valid surrogate measure for coronary atherosclerosis, is a predictor of coronary outcomes and stroke, and is associated with psychosocial stress factors. Stress reduction with the Transcendental Meditation (TM) program decreases coronary heart disease risk factors and cardiovascular mortality in African Americans. B-mode ultrasound is useful for the noninvasive evaluation of carotid atherosclerosis. METHODS: This randomized controlled clinical trial evaluated the effects of the TM program on carotid IMT in hypertensive African American men and women, aged >20 years, over a 6- to 9-month period. From the initially enrolled 138 volunteers, 60 subjects completed pretest and posttest carotid IMT data. The assigned interventions were either the TM program or a health education group. By use of B-mode ultrasound, mean maximum IMT from 6 carotid segments was used to determine pretest and posttest IMT values. Regression analysis and ANCOVA were performed. RESULTS: Age and pretest IMT were found to be predictors of posttest IMT values and were used as covariates. The TM group showed a significant decrease of -0.098 mm (95% CI -0. 198 to 0.003 mm) compared with an increase of 0.054 mm (95% CI -0.05 to 0.158 mm) in the control group (P=0.038, 2-tailed). CONCLUSIONS: Stress reduction with the TM program is associated with reduced carotid atherosclerosis compared with health education in hypertensive African Americans. Further research with this stress-reduction technique is warranted to confirm these preliminary findings.

Black People↗
PubMed2000

Endoscopic plantar fasciotomy for chronic heel pain.

The purpose of our study was to determine whether endoscopic plantar fasciotomy is a safe and effective operation in this patient population. We reviewed our surgical results following endoscopic plantar fasciotomy in sixteen patients (twenty feet) with an average preoperative duration of symptoms of four years. Of the 20 feet, 9 had complete relief of pain while symptoms were improved in nine feet. One patient with bilateral symptoms had no relief in either foot. The average AOFAS hindfoot score improved from 62 to 80, a statistically significant difference. Unilateral patients did better than bilateral with no bilateral patients reporting complete resolution of symptoms. There were no iatrogenic nerve injuries. On the basis of our review, we recommend endoscopic plantar fasciotomy as an alternative to open plantar fascial release for those patients with recalcitrant heel pain.

Chronic Disease↗
PubMed1999

Randomization of the receptor alpha chain recruitment epitope reveals a functional interleukin-5 with charge depletion in the CD loop.

We report the functional phage display of single chain human interleukin-5 (scIL-5) and its use for receptor-binding epitope randomization. Enzyme-linked immunosorbent assays and optical biosensor analyses verified expression of scIL-5 on the phage surface and binding of scIL-5 phage to interleukin-5 receptor alpha chain. Furthermore, an asymmetrically disabled but functional scIL-5 mutant, (wt/A5)scIL-5, was displayed on phage. (wt/A5)scIL-5 was constructed from an N-terminal half containing the original five charged residues (88EERRR92) in the CD loop, including the Glu89 and Arg91 believed key in the alpha chain recognition site, combined with a C-terminal half containing a disabled CD loop sequence (88AAAAA92) missing the key recognition residues. This asymmetric variant was used as a starting point to generate an scIL-5 library in which the intact 88-92 N-terminal CD loop was randomized. From this epitope library, a receptor-binding variant of IL-5 was detected, (SLRGG/A5)scIL-5, in which the only charged residue in the CD loop is an Arg at position 90. Characterization of this variant expressed as a soluble protein in E. coli shows that the IL-5 pharmacophore for receptor alpha chain binding can function with a single positive charge in the CD loop. Charge-depleted CD loop mimetics of IL-5 suggest the importance of charge distribution in functional IL-5 receptor recruitment.

Bacteriophages↗
PubMed1999

Robotic selective sampling and total automation for anti-CMV screening.

The provision of anti-cytomegalovirus (CMV)-negative blood products causes the blood banking community considerable logistical problems. This is due firstly to the fact that only a select group of patients require anti-CMV-negative units, namely the immunocompromised. Secondly, the prevalence of CMV antibody in the blood donor population is high and, thirdly, the demand for anti-CMV-negative blood components continues to increase. To address this problem, a system of robotic selective sampling and total assay automation for anti-CMV screening has been developed. An in-house computer program generates a worklist from the donation database of samples requiring screening to meet clinical demand. Algorithms incorporated in the program ensure that the minimum number of samples possible are selected for provision of anti-CMV-negative products. This 'intelligent' selection of samples substantially reduces reagent cost. Robotic pipetting from the electronically derived worklist, masterplate to test plate robotic transfer and use of an automated assay processor maintains specific sample identification throughout. Results are read mechanically and transmitted directly to the main computer system. Robotic selective sampling and total assay automation produces an efficient, secure, auditable and completely traceable system for the provision of anti-CMV-negative units. The system produced a substantial reduction in labour costs with a 40% reduction in reagent usage. This system can be readily adapted for screening other markers on a selective basis.

Antibodies, Viral↗
PubMed1999

Risk factors for clinically important upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group.

OBJECTIVE: To evaluate the incidence and risk factors for clinically important upper gastrointestinal bleeding in critically ill patients requiring mechanical ventilation. DESIGN: In duplicate, blinded adjudicators determined the presence of clinically important gastrointestinal bleeding using a priori criteria, evaluating relevant clinical, laboratory, and diagnostic data. Cox proportional hazards regression analyses were used to examine baseline and time-dependent risk factors for bleeding. SETTING: Sixteen university-affiliated intensive care units (ICUs) in Canada. PATIENTS: A total of 1,077 critically ill ICU patients ventilated for at least 48 hrs. INTERVENTIONS: Patients were randomized to stress ulcer prophylaxis with intravenous ranitidine or nasogastric sucralfate; otherwise, management was at the discretion of the ICU team. MEASUREMENTS AND MAIN RESULTS: Demographic data included patient characteristics, Acute Physiology and Chronic Health Evaluation II score, and multiple organ dysfunction (MOD) score. Each day in the ICU, physiologic measurements including MOD score, feeding, and other treatment variables were recorded. The significant risk factors for upper gastrointestinal bleeding in the univariable analyses were low platelet count, maximum serum creatinine, maximum MOD score, maximum pulmonary component of the MOD score, maximum hepatic component of the MOD score, maximum renal component of the MOD score, enteral nutrition, and stress ulcer prophylaxis with ranitidine. The only independent predictors of bleeding in the multivariable analysis were maximum serum creatinine (relative risk = 1.16 [95% confidence interval = 1.02-1.32]), enteral nutrition (relative risk = 0.30 [95% confidence interval = 0.13-0.67]), and ranitidine administration (relative risk = 0.39 [95% confidence interval = 0.17-0.83]). CONCLUSIONS: In critically ill ventilated patients, renal failure was independently associated with an increased risk of clinically important gastrointestinal bleeding, whereas enteral nutrition and stress ulcer prophylaxis with ranitidine conferred significantly lower bleeding rates.

APACHE↗
PubMed1999

Evaluation of antibodies to beta2-glycoprotein 1 in the causation of coronary atherosclerosis as part of the antiphospholipid syndrome.

BACKGROUND: Anticardiolipin antibodies (aCL) are associated with accelerated coronary atherosclerosis. Beta2-glycoprotein 1 is a cofactor necessary for the binding of aCL. AIM: The aim of this study was to determine whether antibodies to beta2-glycoprotein 1 (anti-beta2GP1) predispose to coronary artery disease (CAD), and whether the measurement of anti-beta2GP1 will be more useful than aCL alone in the evaluation of coronary risk. METHODS: Persons who had undergone coronary angiography were invited to participate, and risk factors for coronary atherosclerosis recorded. IgG aCL and anti-beta2GP1 were measured and fasting triglyceride (TG) and total cholesterol (TC) levels were determined. Angiographic score (AS) was defined as the number of diseased vessels (0, 1, 2, 3), (>50% stenosis). Ethics Committee approval was obtained. Statistical comparison used the Student's t test and Chi-squared test. RESULTS: Ninety-seven subjects (63 male) with age range 38-81 years (mean 66.0) participated. There were 31 subjects with AS=0, 27 with AS=1, 22 with AS=2, and 17 with AS=3. The three subjects with positive aCL all had CAD, as did three of the four subjects with positive anti-beta2GP1. Among patients with CAD, there was an equal incidence (4.5%, three/66) of aCL and anti-beta2GP1, and an incidence of either aCL or anti-beta2GP1 of 7.6% (five/66). Compared to the group with AS=0, those with AS=1, 2 or 3 comprised a higher mean age (p=0.001) however, there was no significant difference in the prevalence of other coronary risk factors between the two groups. There was no difference in the proportions of patients with either aCL or anti-beta2GP1 in the group with AS=1, 2, or 3, compared to the group with AS=0 (5/66 c.f. 1/31, chi2=0.146, p>0.5). CONCLUSIONS: Our study has not supported an association between anti-beta2GP1 and CAD. The measurement of anti-beta2GP1 (or aCL) in the investigation of premature CAD is not justified on the basis of our results.

Adult↗
PubMed1999

Priming with a secreted form of the fusion protein of respiratory syncytial virus (RSV) promotes interleukin-4 (IL-4) and IL-5 production but not pulmonary eosinophilia following RSV challenge.

The attachment (G) protein of respiratory syncytial virus (RSV) is synthesized as two mature forms: a membrane-anchored form and a smaller secreted form. BALB/c mice scarified with vaccinia virus (VV) expressing the secreted form develop a greater pulmonary eosinophilic influx following RSV challenge than do mice scarified with VV expressing the membrane-anchored form. To determine if a soluble form of an RSV protein was sufficient to induce eosinophilia following RSV challenge, a cDNA that encoded a secreted form of the fusion (F) protein of RSV was constructed and expressed in VV (VV-Ftm(-)). Splenocytes and lung lymphocytes from mice primed with VV-Ftm(-) produced significantly more of the Th2 cytokines interleukin-4 (IL-4) and IL-5 than did mice vaccinated with VV expressing either the native (membrane-anchored) form of the F protein or the G protein. Although mice scarified with VV-Ftm(-) developed a slight increase in the number of pulmonary eosinophils following RSV infection, the increase was not as great as that seen in VV-G-primed mice. Despite the increased IL-4 and IL-5 production and in contrast to mice primed with VV-G, mice primed with VV-Ftm(-) developed RSV-specific cytotoxic T lymphocytes (CTL) and maintained high levels of gamma interferon production. These data demonstrate that recombinant VV strains expressing soluble forms of RSV proteins induce immune responses that are more Th2-like. However, this change alone does not appear sufficient to induce vaccine-augmented disease in the face of active CD8(+) CTL populations.

Animals↗
PubMed1999

Aberrant prostaglandin synthase 2 expression defines an antigen-presenting cell defect for insulin-dependent diabetes mellitus.

Prostaglandins (PGs) are lipid molecules that profoundly affect cellular processes including inflammation and immune response. Pathways contributing to PG output are highly regulated in antigen-presenting cells such as macrophages and monocytes, which produce large quantities of these molecules upon activation. In this report, we demonstrate aberrant constitutive expression of the normally inducible cyclooxygenase PG synthase 2 (PGS(2)/ COX-2) in nonactivated monocytes of humans with insulin-dependent diabetes mellitus (IDDM) and those with islet autoantibodies at increased risk of developing this disease. Constitutive PGS(2) appears to characterize a high risk for diabetes as it correlates with and predicts a low first-phase insulin response in autoantibody-positive subjects. Abnormal PGS(2) expression in at-risk subjects affected immune response in vitro, as the presence of a specific PGS(2) inhibitor, NS398, significantly increased IL-2 receptor alpha-chain (CD25) expression on phytohemagglutinin-stimulated T cells. The effect of PGS(2) on CD25 expression was most profound in subjects expressing both DR04 and DQbeta0302 high-risk alleles, suggesting that this cyclooxygenase interacts with diabetes-associated MHC class II antigens to limit T-cell activation. These results indicate that constitutive PGS(2) expression in monocytes defines an antigen-presenting cell defect affecting immune response, and that this expression is a novel cell-associated risk marker for IDDM.

Adolescent↗
PubMed1999

Expression and activity of vitamin D-metabolizing cytochrome P450s (CYP1alpha and CYP24) in human nonsmall cell lung carcinomas.

Extrarenal 25-hydroxyvitamin D3-1alpha-hydroxylase is believed to play a major role in the pathogenesis of hypercalcemia associated with various types of granulomatous and lymphoproliferative diseases and certain solid tumors. In this paper, we describe the cloning of the cytochrome P450 component of the extrarenal enzyme from a human nonsmall cell lung carcinoma, SW 900. The cytochrome P450 for the extrarenal 1alpha-hydroxylase has an amino acid sequence identical to that of the cytochrome P450 component of the CYP1alpha, the renal form of the enzyme, and appears to be a product of the same gene. CYP1alpha messenger RNA (mRNA) and 1alpha-hydroxylase enzyme activity were detected in two (SW 900, SK-Luci-6) of a series of five nonsmall cell lung carcinoma cell lines. All five lung cell lines were cultured with the same medium under the same conditions, but only two of the five expressed 1alpha-hydroxylase enzyme; two others (WT-E, Calu-1) expressed high levels of the reciprocally regulated enzyme, 25-hydroxyvitamin D3-24-hydroxylase, with its specific cytochrome P450 component, CYP24. Although under basal conditions the lung cell line SW 900 expressed only CYP1alpha and showed 1alpha-hydroxylase enzyme activity, when treated with small concentrations of 1alpha,25-dihydroxyvitamin D3 or high concentrations of 25-hydroxyvitamin D3, it began to express CYP24 and exhibit 24-hydroxylase enzyme activity. Somewhat surprisingly, SW 900 cells still had detectable CYP1alpha mRNA some 24 h after vitamin D treatment despite the fact that 1alpha-hydroxylase enzyme activity was unmeasurable. These data are consistent with the emerging hypothesis that vitamin D through its active form does not directly turn off CYP1alpha mRNA production but, rather, strongly stimulates CYP24, thereby masking CYP1alpha activity. The factor(s) responsible for the basal expression of CYP1alpha in SW 900 and SK-Luci-6 is currently unknown.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1999

PCGs going live.

Explore the source record for details and available documents.

Decision Making, Organizational↗