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Biomedical subjects

D J Cook

Publications and source records attributed to D J Cook.

At least 73 records · Page 4Linked to original sources
PubMed2000

Effect of temperature and PaCO2 on cerebral embolization during cardiopulmonary bypass in swine.

BACKGROUND: Patients experience cerebral embolization during cardiopulmonary bypass (CPB). This study determined if alterations in temperature and/or PaCO2 can reduce cerebral and ocular embolization. METHODS AND RESULTS: Forty-four pigs underwent CPB: 24 animals at 28 degrees C, and 20 at 38 degrees C. The two temperature groups were randomized to undergo embolization (67-microm fluorescent microspheres) at either hypercarbia or hypocarbia. Before and after embolization, cerebral and ocular blood flow were determined at normocarbia. Reducing temperature or PaCO2 reduced cerebral and ocular embolization. Hypocarbia reduced cerebral embolization by 60% and 45% in normothermic and hypothermic groups, respectively (p < 0.0001 and p < 0.05). Relative to normothermic animals, hypothermia reduced cerebral embolization by 37% under an elevated CO2 condition (p < 0.05), but not under hypocarbic conditions. Similarly, regardless of temperature, fewer emboli were delivered to the eye in hypocarbic animals (p < 0.05), but hypothermia did not reduce ocular embolization. CONCLUSIONS: Cerebral embolization is determined by both temperature and PaCO2 at the time of embolization. In CPB practice, reductions in temperature and/or PaCO2 during periods of embolic risk may reduce brain injury.

Animals↗
PubMed2000

Effect of cerebral embolization on regional autoregulation during cardiopulmonary bypass in dogs.

BACKGROUND: Embolization during cardiopulmonary bypass probably alters cerebral autoregulation. Therefore, using laser Doppler flowmetry we investigated the cerebral blood flow velocity changes in response to changes in arterial pressure, before and after embolization in a canine bypass model. METHODS: After Institutional Animal Care and Use Committee approval, 8 anesthetized dogs had a laser Doppler flow probe positioned over the temporoparietal dura. During 37 degrees C cardiopulmonary bypass, the cerebral blood flow velocity response to changing mean arterial pressure (40 to 85 mm Hg in random order) was assessed before and after systemic embolization of 100 mg of 97-microm latex microspheres. RESULTS: Before embolization, cerebral blood flow velocity increased 39% as mean arterial pressure increased from 40 to 85 mm Hg. Following embolization, a 94% increase in cerebral blood flow velocity was demonstrated over the same mean arterial pressure range. The slopes of the curves relating cerebral blood flow velocity to mean arterial pressure were 0.21+/-0.74 and 1.31+/-0.87, before and after embolization (p = 0.016) respectively. CONCLUSIONS: Regional cerebral blood flow autoregulation may be impaired by microembolization known to occur during cardiopulmonary bypass, increasing the dependence of cerebral blood flow on mean arterial pressure.

Animals↗
PubMed2000

The clinical significance of flow cytometry crossmatching in heart transplantation.

OBJECTIVE: Flow cytometry crossmatching (FCXM) is more sensitive than the cytotoxic crossmatch in identifying preformed antibodies to donor alloantigens, but its clinical importance is controversial. The objective of this study was to determine the association of a FCXM with survival and incidence of vascular rejection in cardiac transplant recipients with a negative cytotoxic crossmatch. METHODS: Between 1993 and 1998, 357 heart transplant recipients with a negative T cell cytotoxic crossmatch were studied by three-color FCXM to quantitate anti-donor IgG reactions against B and T lymphocytes. Reactions positive against both were consistent with human leukocyte antigen (HLA) Class I reactivity, and those against B cells only were considered to be against HLA Class II antigens. Endpoints were episodes of vascular rejection, death from acute and chronic rejection and overall survival. RESULTS: Fifty patients were FCXM for Class I-positive, 144 for Class II-positive, and 163 were negative. At 1 month, freedom from vascular rejection was 64% in Class I patients, but 90% and 96% in Class II or negative crossmatch patients (P<0.0001). Survival of the negative crossmatch group was higher than either Class I or II groups (94%, 74% and 76%, respectively, at 3 years; P<0.0001). Death from acute rejection was 3% and 2% at 3 years in negative or Class II-positive patients, but 19% in Class I patients (P<0.0001). Death from chronic rejection occurred only in Class II patients (P=0.002). CONCLUSIONS: Despite a negative T-cell cytotoxic crossmatch, a positive flow cytometry crossmatch correlates with important clinical events after heart transplantation.

Adolescent↗
PubMed2000

Bypass flow, mean arterial pressure, and cerebral perfusion during cardiopulmonary bypass in dogs.

OBJECTIVE: To determine if normal cardiopulmonary bypass (CPB) pump flows maintain cerebral perfusion in the context of reduced mean arterial pressure at 33 degrees C. DESIGN: A prospective investigation. SETTING: Animal CPB research laboratory. PARTICIPANTS: Seven dogs that underwent CPB. INTERVENTIONS: Seven dogs underwent CPB at 33 degrees C using alpha-stat management and a halothane, fentanyl-midazolam anesthetic. Cerebral blood flow was measured using the sagittal sinus outflow technique. After control measurements at 70 mm Hg, cerebral physiologic values were determined under four conditions in random order: (1) mean arterial pressure of 60 mm Hg achieved by a reduction in pump flow, (2) mean arterial pressure of 60 mmHg determined by partial opening of a femoral arterial-to-venous reservoir shunt, (3) mean arterial pressure of 45 mm Hg by reduced pump flow, and (4) mean arterial pressure of 45 mm Hg by shunt. A 9F femoral arterial-to-venous reservoir shunt was controlled by a screw clamp. MEASUREMENTS AND MAIN RESULTS: Except for the controlled variables of mean arterial pressure and bypass flow, physiologic determinants of cerebral blood flow (temperature, PaCO2 and hematocrit) did not differ under any of the CPB conditions. Pump flow per se was not a determinant of cerebral perfusion. Cerebral blood flow and cerebral oxygen delivery did not differ with changes in pump flow if mean arterial pressure did not differ. Cerebral blood flow depended on mean arterial pressure under all pump flow conditions, however. CONCLUSIONS: Over the range of flows typical in adult CPB at 33 degrees C, pump flow does not have an effect on cerebral perfusion independent of its effect on mean arterial pressure. A targeted pump flow per se is not sufficient to maintain cerebral perfusion if mean arterial blood pressure is reduced.

Animals↗
PubMed2000

Using practice guidelines to allocate medical technologies. An ethics framework.

Clinical practice guidelines are expanding their scope of authority from clinical decision making to collective policy making, and promise to gain ground as resource allocation tools in coming years. A close examination of how guidelines approach patient selection criteria offers insight into their ethical implications when used as resource allocation or rationing instruments. The purposes of this paper are: a) to examine the structure of allocative reasoning found in clinical guidelines; b) to identify the ethical principles implied and compare how guidelines enact these principles with how explicit systems-level rationing exercises and health policy analyses have approached them; and c) to offer some preliminary suggestions for how these ethical issues might be addressed in the process of guideline development. The resulting framework can be used by guideline developers and users to understand and address some of the ethical issues raised by guidelines for the use of scarce technologies.

Biomedical Technology↗
PubMed2000

Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. QUOROM Group.

BACKGROUND: The Quality of Reporting of Meta-analyses (QUOROM) conference was convened to address standards for improving the quality of reporting of meta-analyses of clinical randomised controlled trials (RCTs). METHODS: The QUOROM group consisted of 30 clinical epidemiologists, clinicians, statisticians, editors, and researchers. In conference, the group was asked to identify items they thought should be included in a checklist of standards. Whenever possible, checklist items were guided by research evidence suggesting that failure to adhere to the item proposed could lead to biased results. A modified Delphi technique was used in assessing candidate items. FINDINGS: The conference resulted in the QUOROM statement, a checklist, and a flow diagram. The checklist describes our preferred way to present the abstract, introduction, methods, results, and discussion sections of a report of a meta-analysis. It is organised into 21 headings and subheadings regarding searches, selection, validity assessment, data abstraction, study characteristics, and quantitative data synthesis, and in the results with 'trial flow', study characteristics, and quantitative data synthesis; research documentation was identified for eight of the 18 items. The flow diagram provides information about both the numbers of RCTs identified, included, and excluded and the reasons for exclusion of trials. INTERPRETATION: We hope this report will generate further thought about ways to improve the quality of reports of meta-analyses of RCTs and that interested readers, reviewers, researchers, and editors will use the QUOROM statement and generate ideas for its improvement.

Data Collection↗
PubMed2000

The use and misuse of immunologic monitoring after transplantation: approaches that have proved useful.

Current practice in the monitoring of cardiac transplants revolves around the use of the endomyocardial biopsy. While this is effective for the identification of an ongoing immune response in the graft, for years investigators have explored less invasive approaches in the hope of achieving the same goal by examining the patient's immune response. For a number of years, lymphocytes, their subsets, and their level of activation in the periphery were investigated. To a large degree, it was a lack of specificity in these approaches that led to their falling out of favor. Examination of donor-specific reactivity by means of lymphocyte proliferation assays has also been used; however, these approaches have been impeded by the time and effort required to accomplish them. During the last few years, flow cytometric cross-matching during the posttransplant period has been used at our institution. While this cross-matching focuses on the humoral immune responses, we have found it to be of value in identifying patients at risk of rejection and in allowing the assessment of treatment modalities used to treat ongoing rejection. While the perfect approach remains to be found, the potential advantages of immunologic monitoring would seem to justify continued study.

Antibody Formation↗
PubMed2000

Interobserver variation in interpreting chest radiographs for the diagnosis of acute respiratory distress syndrome.

To measure the reliability of chest radiographic diagnosis of acute respiratory distress syndrome (ARDS) we conducted an observer agreement study in which two of eight intensivists and a radiologist, blinded to one another's interpretation, reviewed 778 radiographs from 99 critically ill patients. One intensivist and a radiologist participated in pilot training. Raters made a global rating of the presence of ARDS on the basis of diffuse bilateral infiltrates. We assessed interobserver agreement in a pairwise fashion. For rater pairings in which one rater had not participated in the consensus process we found moderate levels of raw (0.68 to 0.80), chance-corrected (kappa 0.38 to 0.55), and chance-independent (Phi 0. 53 to 0.75) agreement. The pair of raters who participated in consensus training achieved excellent to almost perfect raw (0.88 to 0.94), chance-corrected (kappa 0.72 to 0.88), and chance-independent (Phi 0.74 to 0.89) agreement. We conclude that intensivists without formal consensus training can achieve moderate levels of agreement. Consensus training is necessary to achieve the substantial or almost perfect levels of agreement optimal for the conduct of clinical trials.

Adult↗
PubMed2000

Binding of some Diocleinae lectins to the mucosal surfaces of the eye and mouth.

Controlled delivery of diagnostic or therapeutically active agents to the eye and oral cavity is limited by the efficient removal mechanisms that exist in these areas. In this work, recently isolated, purified and characterised Brazilian bean lectins were examined for their ability to bind to the buccal and sublingual mucosa, cornea and conjunctiva of rat, with regard to their potential therapeutic use. These lectins were labelled using biotin (long arm) N-hydroxysuccinimide ester and a technique developed at the University of Portsmouth. Evaluation of binding after 15 min contact with intact (unfixed) rat eye and oral cavity epithelia was completed using a standard histological procedure involving the avidin-biotin reaction and formation of a brown precipitate with a 3,3'-diaminobenzidine solution. When examined by affinity chromatography, all lectins studied were found to show high percentage biotinylation (i.e. less than 4% by weight of total lectin was eluted from the column). The lectin:biotin ratio was estimated using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), and ranged between 1:2 (Cratylia floribunda) and 1:10.4 (Canavalia brasilensis). As with previous studies, all lectins bound to the mucosal surfaces to some extent--the Cratylia floribunda lectin appearing to be the most promising, whereas the Dioclea violacea lectin showed comparatively weak binding. In all cases, the presence of glucose (the hapten sugar) reduced or eliminated binding. It was concluded that glucose-mannose binding sites are present on these surfaces, and the lectins from C. floribunda showed a particular affinity for these.

Animals↗
PubMed1999

Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of Reporting of Meta-analyses.

BACKGROUND: The Quality of Reporting of Meta-analyses (QUOROM) conference was convened to address standards for improving the quality of reporting of meta-analyses of clinical randomised controlled trials (RCTs). METHODS: The QUOROM group consisted of 30 clinical epidemiologists, clinicians, statisticians, editors, and researchers. In conference, the group was asked to identify items they thought should be included in a checklist of standards. Whenever possible, checklist items were guided by research evidence suggesting that failure to adhere to the item proposed could lead to biased results. A modified Delphi technique was used in assessing candidate items. FINDINGS: The conference resulted in the QUOROM statement, a checklist, and a flow diagram. The checklist describes our preferred way to present the abstract, introduction, methods, results, and discussion sections of a report of a meta-analysis. It is organised into 21 headings and subheadings regarding searches, selection, validity assessment, data abstraction, study characteristics, and quantitative data synthesis, and in the results with "trial flow", study characteristics, and quantitative data synthesis; research documentation was identified for eight of the 18 items. The flow diagram provides information about both the numbers of RCTs identified, included, and excluded and the reasons for exclusion of trials. INTERPRETATION: We hope this report will generate further thought about ways to improve the quality of reports of meta-analyses of RCTs and that interested readers, reviewers, researchers, and editors will use the QUOROM statement and generate ideas for its improvement.

Authorship↗
PubMed1999

Life support in the intensive care unit: a qualitative investigation of technological purposes. Canadian Critical Care Trials Group.

BACKGROUND: The ability of many intensive care unit (ICU) technologies to prolong life has led to an outcomes-oriented approach to technology assessment, focusing on morbidity and mortality as clinically important end points. With advanced life support, however, the therapeutic goals sometimes shift from extending life to allowing life to end. The objective of this study was to understand the purposes for which advanced life support is withheld, provided, continued or withdrawn in the ICU. METHODS: In a 15-bed ICU in a university-affiliated hospital, the authors observed 25 rounds and 11 family meetings in which withdrawal or withholding of advanced life support was addressed. Semi-structured interviews were conducted with 7 intensivists, 5 consultants, 9 ICU nurses, the ICU nutritionist, the hospital ethicist and 3 pastoral services representatives, to discuss patients about whom life support decisions were made and to discuss life-support practices in general. Interview transcripts and field notes were analysed inductively to identify and corroborate emerging themes; data were coded following modified grounded theory techniques. Triangulation methods included corroboration among multiple sources of data, multidisciplinary team consensus, sharing of results with participants and theory triangulation. RESULTS: Although life-support technologies are traditionally deployed to treat morbidity and delay mortality in ICU patients, they are also used to orchestrate dying. Advanced life support can be withheld or withdrawn to help determine prognosis. The tempo of withdrawal influences the method and timing of death. Decisions to withhold, provide, continue or withdraw life support are socially negotiated to synchronize understanding and expectations among family members and clinicians. In discussions, one discrete life support technology is sometimes used as an archetype for the more general concept of technology. At other times, life-support technologies are discussed collectively to clarify the pursuit of appropriate goals of care. CONCLUSIONS: The orchestration of death involves process-oriented as well as outcome-oriented uses of technology. These uses should be considered in the assessment of life-support technologies and directives for their appropriate use in the ICU.

Attitude of Health Personnel↗
PubMed1999

The rational clinical examination. Does this adult patient have acute meningitis?

CONTEXT: Early clinical recognition of meningitis is imperative to allow clinicians to efficiently complete further tests and initiate appropriate therapy. OBJECTIVE: To review the accuracy and precision of the clinical examination in the diagnosis of adult meningitis. DATA SOURCES: A comprehensive review of English- and French-language literature was conducted by searching MEDLINE for 1966 to July 1997, using a structured search strategy. Additional references were identified by reviewing reference lists of pertinent articles. STUDY SELECTION: The search yielded 139 potentially relevant studies, which were reviewed by the first author. Studies were included if they described the clinical examination in the diagnosis of objectively confirmed bacterial or viral meningitis. Studies were excluded if they enrolled predominantly children or immunocompromised adults or focused only on metastatic meningitis or meningitis of a single microbial origin. A total of 10 studies met the criteria and were included in the analysis. DATA EXTRACTION: Validity of the studies was assessed by a critical appraisal of several components of the study design. These components included an assessment of the reference standard used to diagnose meningitis (lumbar puncture or autopsy), the completeness of patient ascertainment, and whether the clinical examination was described in sufficient detail to be reproducible. DATA SYNTHESIS: Individual items of the clinical history have low accuracy for the diagnosis of meningitis in adults (pooled sensitivity for headache, 50% [95% confidence interval [CI], 32%-68%]; for nausea/vomiting, 30% [95% CI, 22%-38%]). On physical examination, the absence of fever, neck stiffness, and altered mental status effectively eliminates meningitis (sensitivity, 99%-100% for the presence of 1 of these findings). Of the classic signs of meningeal irritation, only 1 study has assessed Kernig sign; no studies subsequent to the original report have evaluated Brudzinski sign. Among patients with fever and headache, jolt accentuation of headache is a useful adjunctive maneuver, with a sensitivity of 100%, specificity of 54%, positive likelihood ratio of 2.2, and negative likelihood ratio of 0 for the diagnosis of meningitis. CONCLUSIONS: Among adults with a clinical presentation that is low risk for meningitis, the clinical examination aids in excluding the diagnosis. However, given the seriousness of this infection, clinicians frequently need to proceed directly to lumbar puncture in high-risk patients. Many of the signs and symptoms of meningitis have been inadequately studied, and further prospective research is needed.

Acute Disease↗
PubMed1999

Users' guides to the medical literature: XVI. How to use a treatment recommendation. Evidence-Based Medicine Working Group and the Cochrane Applicability Methods Working Group.

Clinicians can often find treatment recommendations in traditional narrative reviews and the discussion sections of original articles and meta-analyses. Making a treatment recommendation involves framing a question, identifying management options and outcomes, collecting and summarizing evidence, and applying value judgments or preferences to arrive at an optimal course of action. Each step in this process can be conducted systematically (thus protecting against bias) or unsystematically (leaving the process open to bias). Clinicians faced with a plethora of recommendations may wish to attend to those that are less likely to be biased. Therefore, we propose a hierarchy of rigor of recommendations to guide clinicians when judging the usefulness of particular recommendations. Recommendations with the highest rigor consider all relevant options and outcomes, include a comprehensive collection of the methodologically highest quality data with an explicit strategy for summarizing the data (that is, a systematic review), and make an explicit statement of the values or preferences involved in moving from evidence to action. High rigor recommendations come from systematically developed, evidence-based practice guidelines or rigorously conducted decision analyses. Systematic reviews, which typically do not consider all relevant options and outcomes or make the preferences underlying recommendations explicit, offer intermediate rigor recommendations. Traditional approaches in which the collection and assessment of evidence remains unsystematic, all relevant options and outcomes may not be considered, and values remain implicit, provide recommendations of weak rigor. In an era in which clinicians are barraged by recommendations as to how to manage their patients, this hierarchy provides a potentially useful set of guides.

Decision Making↗