Search PubMed⌕ Search

Biomedical subjects

D J Cook

Publications and source records attributed to D J Cook.

At least 127 records · Page 7Linked to original sources

Critical cerebral perfusion pressure during tepid heart operations in dogs.

BACKGROUND: The management of blood pressure during cardiopulmonary bypass varies widely. This may be particularly relevant with the trend to warmer bypass temperatures and an older patient population. Therefore, we examined the minimal perfusion pressure that maintains cerebral oxygen delivery during cardiopulmonary bypass at 33 degrees C. METHODS: Ten dogs were placed on bypass and body temperature was reduced to 33 degrees C (alpha-stat pH management). At six randomly ordered mean arterial blood pressures (35, 40, 45, 50, 60, and 70 mm Hg), cerebral blood flow, oxygen delivery, and metabolic rate were determined. RESULTS: Cerebral oxygen delivery was stable if the mean arterial pressure was greater than or equal to 60 mm Hg. If mean arterial pressure was less than or equal to 50 mm Hg, cerebral oxygen delivery decreased, and at less than 45 mm Hg cerebral ischemia was seen. CONCLUSIONS: In a dog without vascular disease, the brain becomes perfusion pressure-dependent at a mean arterial pressure of approximately 50 mm Hg. There is no leftward shift of the cerebral autoregulatory curve during bypass at 33 degrees C. Greater support of mean arterial pressure during "tepid" cardiopulmonary bypass is indicated in the current adult surgical population that is older and has vascular comorbidity.

Animals↗

Hemodilution and whole body oxygen balance during normothermic cardiopulmonary bypass in dogs.

OBJECTIVE: The purpose of this study was to determine the minimum hematocrit value that can support whole body oxygen consumption during normothermic cardiopulmonary bypass. The effect of hemodilution on peripheral resistance, whole body oxygen delivery, and oxygen consumption was determined over a range of hematocrit values. METHODS: Measurements were obtained during 38 degrees C cardiopulmonary bypass with progressive normovolemic hemodilution (hematocrit value 40% to 9%) in nine dogs. Dextran 70 (6%) was used as a diluent. Anesthesia consisted of high-dose fentanyl and midazolam. A mean arterial pressure of 60 mm Hg was maintained throughout cardiopulmonary bypass via increases in pump flow. RESULTS: Progressive hemodilution was associated with a decreasing total peripheral resistance. During normothermic cardiopulmonary bypass with a whole blood prime, the whole body oxygen consumption approximated values previously reported in dogs under nonbypass conditions. Oxygen delivery and whole body oxygen uptake were maintained between a hematocrit value of 39% and 25%. Significant decreases for both were seen when the hematocrit value was reduced to 18% and below. CONCLUSIONS: A hematocrit level greater than 18% was needed to maintain systemic oxygen delivery and consumption during warm cardiopulmonary bypass. The critical hematocrit value may be higher under bypass than nonbypass conditions because the flow increases that are practical during cardiopulmonary bypass do not approximate those seen in response to hemodilution of the intact circulation. Finally, the critical hematocrit value for the body may be higher than that required for the brain during warm cardiopulmonary bypass.

Animals↗

HLA-DP: a class II restriction molecule involved in epitope spreading during the development of multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system. It is widely believed that complex polygenic inheritance patterns involving HLA-DR and -DQ class II genes contribute to MS susceptibility, and current evidence indicates that disease risk vs disease outcome may be associated with distinctly different HLA class II alleles. We have recently shown that the early development of MS is accompanied by an extensive plasticity of myelin self-recognition with the acquisition of neo-autoreactivity, or epitope spreading, as a prominent feature. Although we did not observe a common determinant recognized by patients sharing identical HLA-DR or -DQ class II alleles, we did observe epitope spreading to the p50-63 determinant of myelin proteolipid protein (PLP) in two study subjects showing complete disparity at HLA-DR and -DQ but identity at the HLA-DP allele DPB1*0301. In the present study we show that self-recognition during the early stages in the development of MS involves HLA-DP class II restricted responses to the PLP 50-63 spreading determinant. Our results suggest that self-presentation by HLA-DP may play an important role in epitope spreading and in the propagation of self-recognition during the clinical progression of MS.

Adult↗

Evidence-based medicine. A tool for enhancing critical care practice.

Evidence-based medicine (EBM) involves caring for patients by explicitly integrating clinical research evidence with pathophysiologic reasoning, caregiver experience, and patient preferences. EBM is a style of practice and teaching which may also help plan future research. This article discusses the application of EBM to critical care.

Critical Care↗

Prognosis in anoxic and traumatic coma.

This article presents a systematic review of the prognostic factors in coma caused by hypoxia and anoxia, and traumatic head injury. In the case of anoxic coma, poor prognosis can be determined very accurately at the bedside by the lack of brainstem reflexes assessed at day three post-insult. Electroencephalogram (EEG) and evoked potentials (i.e., auditory and somatosensory) detect additional patients with poor prognosis. Clinical examination is not as helpful in the case of traumatic coma. Evoked potentials performed within the first week detect approximately half of patients with a poor prognosis. EEG adds only a small amount of prognostic information.

Adult↗

Vascular rejection post heart transplantation is associated with positive flow cytometric cross-matching.

OBJECTIVE: Use of flow cytometry cross-matching for measurement of donor-specific alloreactivity and monitoring anti-donor antibodies is well established. This study was performed to determine (1) its accuracy as a marker of vascular rejection, (2) its correlation with post-transplant outcome and (3) its ability to monitor highly sensitized patients requiring antibody removal with plasma exchange. METHODS: Serial serum samples from 99 heart transplant recipients were examined for the presence of anti-donor antibodies of the IgG class that were reactive with T and/or B cryopreserved donor lymphocytes. A sub-group of 20 HLA sensitized patients required plasma exchange to remove the anti-HLA antibodies and were monitored with flow cytometry cross-matching to assess the degree of antibody removal. RESULTS: Positive T-cell reactions were observed in 26 patients and positive B-cell reactions in 54. Twenty patients had vascular rejection. A significantly larger number of patients with a positive flow cytometry cross-match had vascular rejection (42% versus 12% for T-cell reactions, and 32% versus 7% for B-cell reactions; P = 0.002 each). Of the patients who had vascular rejection, 11 had a positive T-cell reaction (flow cytometry cross-match sensitivity of 55%), and 17 had a positive B-cell reaction (sensitivity of 85%). Of the 79 patients who did not develop vascular rejection, 64 had a negative T-cell reaction (specificity of 81%), and 42 had a negative B-cell reaction (specificity of 53%). The actuarial 2-year survival estimates were significantly higher in patients with negative T-cell reactions (90% versus 75%; P = 0.04), and B-cell reactions (95% versus 78%; P = 0.02). In the highly sensitized subgroup (n = 20) the effectiveness of plasma exchange to decrease anti-HLA antibody reactivity was a strong predictor of outcome. For patients in whom plasma exchange (PE) reduced anti-donor reactivity, 1-year survival was 87% compared to 25% in those whom PE did not reduce the level of antibody binding as assessed with flow cytometry cross-matching (P < 0.0001). CONCLUSIONS: Flow cytometry cross-matching provides a valuable marker for the detection of vascular rejection after cardiac transplantation. Quantitative measurements may allow evaluation of the efficacy of treatment modalities employed in the management of vascular rejection in an attempt to improve outcome.

Actuarial Analysis↗

Normothermic cardiopulmonary bypass increases heparin requirements necessary to maintain anticoagulation.

OBJECTIVE: With the practice of warm cardiopulmonary bypass (CPB) at our institution we have observed an apparent increase in heparin requirements. CPB temperature predictability affects pharmacokinetics and differences in drug metabolism can be expected. We hypothesized that heparin requirements would increase with increasing CPB temperature. METHODS: Following Institutional Review Board approval, we reviewed the charts of 354 patients undergoing primary coronary artery bypass graft surgery. We recorded patient demographic data, CPB duration, heparin requirements, and temperature during CPB. CPB was conducted between 24 degrees C and 37 degrees C. The Spearman's correlation coefficient, Pearson chi-square, and rank-sum tests were used for data analysis. RESULTS: Core temperature during CPB correlated with heparin requirements (r = 0.13, p < 0.02). However, CPB duration was shorter in warm patients than in cold patients (r = -0.455, p < 0.0001). Additional heparin requirements adjusted for duration of CPB (units/minute) were also significantly greater in the warm group (p = 0.018). CONCLUSIONS: Maintenance of adequate heparin anticoagulation during CPB is clinically important. Warm CPB patients required more heparin per minute than those undergoing cold CPB. More frequent assessment of anticoagulation and administration of additional heparin should be considered in patients undergoing warm CPB.

Aged↗

Development of a questionnaire to measure quality of life in patients with irritable bowel syndrome.

OBJECTIVE: To develop a questionnaire for measuring health-related quality of life (HRQL) in patients with Irritable Bowel Syndrome (IBS). METHODS: We surveyed the existing literature, and interviewed patients and clinicians, to develop a list of 182 potential problems for IBS patients. One hundred patients with IBS completed a questionnaire in which they told us whether each of the 182 items was a problem for them, and if so the magnitude of their importance in their lives. RESULTS: Patients identified four major problem areas: bowel symptoms, fatigue, activity limitations, and emotional dysfunction. On the basis of these findings, we constructed a 26-item questionnaire which, in pre-testing, 16 patients found clear and easy to complete. CONCLUSION: We have developed a questionnaire that measures HRQL in IBS patients and is suitable for use as an outcome measure in clinical trials in IBS.

Activities of Daily Living↗

Telekid Care: bringing health care into schools.

BACKGROUND: Telekid Care is a project that attempts to overcome the health and educational barriers faced by children in urban Kansas City, Kansas. Telemedicine units were placed in school nurses' offices and linked to physicians at the University of Kansas Medical Center (KUMC). This paper describes the development of this project, presents utilization data, and discuss the lessons learned from the application of telemedicine in a school setting. RESULTS: Project developers spent 11 months designing the protocol and procedures for a pilot test. Four elementary schools participated, and 187 consultations were conducted. The most common reason for consultation was ear, nose, and throat (ENT) problems, making up 28% of all consults. Mandatory school physical examinations and dermatology problems combined to make up an additional 40% of the consults. The average time that elapsed between the request for a consult and confirmation of an appointment was 23 minutes. When immediate service was requested, 85% of the consults occurred the day of the request. These results strongly demonstrate telemedicine's ability to offer immediate service to children in need. CONCLUSION: Telemedicine enabled underserved inner-city children to gain access to health services. This service was most effective when it was integrated into the delivery system. Furthermore, community groups strongly favored the project, positively influencing its acceptance as an innovative health care delivery system.

Appointments and Schedules↗

Confidence in life-support decisions in the intensive care unit: a survey of healthcare workers. Canadian Critical Care Trials Group.

OBJECTIVE: To examine the relationship between intensive care unit (ICU) healthcare workers' confidence and their decision to withdraw life support. DESIGN: Cross-sectional survey of Canadian intensivists, ICU housestaff, and bedside nurses. Respondents chose the level of care (from comfort measures only to full aggressive care) for 12 patients described in clinical scenarios, and rated their confidence in their decisions. SETTING: Thirty-seven Canadian university-affiliated hospitals. PATIENTS: None. INTERVENTIONS: We used discrete data analysis models to examine the association between the chosen level of care, confidence in the decisions, the clinical scenario, and healthcare worker group. MEASUREMENTS AND MAIN RESULTS: The response rate was 1,361 (76%)/1,795; for this analysis, we used data from 1,306 respondents with completed questionnaires. Responses for each scenario varied widely among respondents. The level of care chosen was dependent on the scenario, the healthcare worker group, and the confidence with which the decisions were made (p < .001 for each). Intensivists were less aggressive than the ICU nurses, who were less aggressive than the housestaff, but the magnitude of effect was small. Overall, respondents were very confident about their decisions 34% of the time. After adjustment for clinical scenario and chosen level of care, intensivists were more confident than nurses, who were more confident than housestaff (40% of intensivists, 29% of nurses, and 23% of housestaff were very confident). In general, healthcare workers tended to be more confident when they chose extreme levels of care than when they chose intermediate levels of care. Considerable variability in responses to scenarios remained even when we considered only those responses made with the highest level of confidence. CONCLUSIONS: While confidence in decisions about withdrawal of life support increases with seniority and authority, consistency of decisions may not. When given standard information, healthcare workers can make contradictory decisions yet still be very confident about the level of care they would administer.

Aged↗

Frequency and methodologic rigor of quality-of-life assessments in the critical care literature.

OBJECTIVES: To present a framework for describing/measuring quality of life (QOL) and health-related quality of life (HRQL), and to assess the frequency and methodologic rigor of QOL studies in the adult critical care literature. DATA SOURCES: Computerized bibliographic search of published research, manual search of key intensive care unit (ICU) journals, and citation review of relevant articles. STUDY SELECTION: We manually searched Critical Care Medicine, American Journal of Respiratory and Critical Care Medicine, and Intensive Care Medicine for the period January 1992 to July 1995 to assess the frequency of published QOL studies. Combined with a computerized bibliographic search, we found 64 studies that met our criteria that reported on patient-related outcomes (other than mortality) after hospital discharge. DATA EXTRACTION: We abstracted data on the nature of each study, the instruments used to measure QOL, and the methodologic rigor of the QOL assessments. We evaluated each study using criteria we developed to assess the validity of HRQL measurements. MEASUREMENTS AND MAIN RESULTS: In our manual search, we found 1,073 articles relevant to the practice of adult critical care. Of these, 19 (1.7%)/1073 included QOL measurements. Combined with our comprehensive search strategy, we found 64 papers that evaluated QOL in ICU patients. These papers dealt primarily with issues of: prognosis (32 [50%]), resource allocation (23 [36%]), and clinical prediction (9 [14%]). We found no randomized trials that included post-ICU QOL as an outcome. With respect to the validity of the HRQL assessments, 63/64 (98%) studies evaluated aspects of patients' lives that we considered important. Thirty-three (52%) studies were limited in scope to specific aspects of HRQL, and 31 (48%) studies covered broad areas of HRQL. In these 64 studies, there were 108 different instruments used. The reliability and validity of the instruments used were reported in 7 (6%) and 15 (14%) cases, respectively. For 81 (75%) instruments, the investigators either explained the results or used informative, qualitative descriptors whose interpretation was self-evident. Overall, three (5%) of the included studies met all four methodologic criteria to assess the validity of HRQL assessments. CONCLUSIONS: QOL assessments occur infrequently in the ICU literature and are of limited methodologic quality. More studies using valid and reliable instruments are necessary to document the long-term QOL of critically ill patients, especially those at risk of a "poor" outcome.

Adult↗

How to use practice guidelines in the intensive care unit: Diagnosis and management of unstable angina.

OBJECTIVE: Practice guidelines are often based on expert opinion, and are sometimes based on research evidence, but are usually a mix of both. The goal of this article is to aid in the evaluation of the validity of practice guidelines. DATA SYNTHESIS: The Agency for Health Care Policy and Research Practice Guideline on Management of Unstable Angina and other relevant primary and synthetic research. METHODS: Critical appraisal of guidelines requires understanding how guideline developers identified, appraised, and summarized the evidence, and how they chose the values reflected in their recommendations. To determine whether guidelines are applicable in our practice, we look for clear and concise recommendations about specific populations, describing common options linked to clinically important outcomes. Guidelines must be considered in light of local skills, culture, and resources, and need to be individualized to different patients and settings. CONCLUSIONS: As better evidence and new clinical insights emerge, guidelines require updating. The ultimate value of a guideline is determined by evaluating its effect on process of care, resource utilization, and most importantly, patient outcomes.

Angina, Unstable↗

How to use a review article: prophylactic endoscopic sclerotherapy for esophageal varices. Evidence Based Critical Care Medicine Group.

OBJECTIVE: To assess the validity of a meta-analysis about sclerotherapy for the primary prevention of bleeding from esophageal varices, to interpret the results, and discuss whether they apply in practice. DATA SOURCES: Critical appraisal techniques for systematic reviews. DATA EXTRACTION: Systematic reviews are distinct from narrative reviews in that they answer specific clinical questions, and have explicit and reproducible methods for searching, selecting, and appraising the primary studies, to create the most valid synthesis of the evidence. DATA SYNTHESIS: Meta-analyses are systematic reviews containing a critical appraisal and statistical summary of individual study results and their confidence limits, whereas qualitative systematic reviews provide a narrative executive summary of study results. CONCLUSIONS: High-quality systematic reviews are being used increasingly to guide practice, strengthening the link between research results and improved health outcomes. Understanding their strengths and limitations helps us to use them appropriately in practice.

Critical Care↗

Tunneling short-term central venous catheters to prevent catheter-related infection: a meta-analysis of randomized, controlled trials.

OBJECTIVE: To evaluate the efficacy of tunneling short-term central venous catheters to prevent catheter-related infections. DATA SOURCES: MEDLINE, EMBASE, conference proceedings, citation review of relevant primary and review articles, personal files, and contact with expert informants. STUDY SELECTION: From a pool of 225 randomized, controlled trials of venous and arterial catheter management, we identified 12 relevant trials and included seven of these trials in the analysis. DATA EXTRACTION: In duplicate, independently, we abstracted data on the population, intervention, outcomes, and methodologic quality. DATA SYNTHESIS: Tunneling decreased bacterial colonization of the catheter by 39% (relative risk of 0.61; 95% confidence interval [CI] of 0.39 to 0.95) and decreased catheter-related sepsis with bacteriologic confirmation by 44% (relative risk of 0.56; 95% CI of 0.31 to 1) in comparison with standard placement. The majority of the benefit in the decreased rate of catheter-sepsis came from one trial at the internal jugular site (relative risk of 0.30, 95% CI of 0.10 to 0.89) and the reduction in risk was not significant when the data from five subclavian catheter trials were pooled (relative risk of 0.71, 95% CI of 0.36 to 1.43). Tunneling was not associated with increased risk of mechanical complications from placement or technical difficulties during placement. However, this outcome was not rigorously evaluated. CONCLUSIONS: Tunneling decreases central venous catheter-related infections. However, current evidence does not support routine tunneling until its efficacy is evaluated at different placement sites and relative to other interventions.

Bacteremia↗

Benefit of heparin in central venous and pulmonary artery catheters: a meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the effect of heparin on thrombus formation and infection associated with use of central venous and pulmonary artery catheters. DATA SOURCES: We used MEDLINE, EMBASE, citation review of relevant primary and review articles, personal files, and contact with expert informants. STUDY SELECTION: Fourteen randomized controlled trials evaluating prophylactic doses of heparin or heparin bonding were included. DATA EXTRACTION: In duplicate, independently, we abstracted data on the population, intervention, outcome, and methodologic quality. DATA SYNTHESIS: Prophylactic heparin decreases catheter-related venous thrombosis (relative risk [RR], 0.43; 95% confidence interval [CI], 0.23, 0.78) and bacterial colonization (RR, 0.18; 95% CI, 0.06, 0.60) of central venous catheters and may decrease catheter-related bacteremia (RR, 0.26; 95% CI, 0.07, 1.03). Heparin bonding decreases the risk of pulmonary artery catheter clot formation within 24 h (RR, 0.08; 95% CI, 0.02, 0.37). CONCLUSIONS: Heparin administration effectively reduces thrombus formation and may reduce catheter-related infections in patients who have central venous and pulmonary artery catheters in place. Cost-effectiveness comparisons of unfractionated heparin, low molecular weight heparin, and warfarin are needed.

Adult↗

The effect of positive pressure airway support on mortality and the need for intubation in cardiogenic pulmonary edema: a systematic review.

OBJECTIVE: To critically appraise and summarize the trials examining the addition of continuous positive airway pressure (CPAP) or noninvasive positive pressure ventilation (NPPV) to standard therapy on hospital mortality, need for endotracheal intubation, and predischarge left ventricular function in patients admitted to the hospital with cardiogenic pulmonary edema with gas exchange abnormalities. DATA SOURCES: We searched MEDLINE (1983 to June 1997) and bibliographies of all selected articles and review articles. We also reviewed the abstracts from the proceedings of relevant meetings from 1985 to 1997. STUDY SELECTION: (1) POPULATION: patients presenting to hospital with cardiogenic pulmonary edema; (2) intervention: one of the following three: (a) the use of CPAP and standard medical therapy vs standard medical therapy alone; (b) the use of NPPV and standard medical therapy vs standard medical therapy alone; and (c) the use of NPPV and standard therapy vs CPAP and standard therapy; (3) outcome: hospital survival, need for endotracheal intubation, or predischarge left ventricular dysfunction; and (4) study design: randomized controlled trial (RCT); if there were fewer than two RCTs, other study designs were included. DATA EXTRACTION: Two authors independently extracted data and evaluated the methodologic quality of the studies. DATA SYNTHESIS: CPAP was associated with a decrease in need for intubation (risk difference, -26%, 95% confidence intervals, -13 to -38%) and a trend to a decrease in hospital mortality (risk difference, -6.6%; +3 to -16%) compared with standard therapy alone. There was insufficient evidence to comment on the effectiveness of NPPV either compared with standard therapy or CPAP and standard therapy. Evidence was also lacking on the potential for either intervention to cause harm. CONCLUSIONS: A modest amount of favorable experimental evidence exists to support the use of CPAP in patients with cardiogenic pulmonary edema. CPAP appears to decrease intubation rates and data suggest a trend toward a decrease in mortality, although the potential for harm has not been excluded. The role of NPPV in this setting requires further study before it can be widely recommended.

Clinical Trials as Topic↗

Flow cytometry crossmatching (FCXM) in the UNOS Kidney Transplant Registry.

1. Among 5,776 transplants reported to the UNOS Scientific Renal Transplant Registry with flow cytometry crossmatch (FCXM) results, 13% had a positive FCXM. The majority (8.8%) had B-cell only reactivity and the remaining 4.2% had T-cell reactivity. 2. Retransplanted patients, females and sensitized patients were more likely to have been FCXM positive than primary transplants, males, or unsensitized patients. 3. A positive FCXM was associated with less than optimal function as evidenced by an increased need for posttransplant dialysis, more grafts that never functioned, longer hospital stays and a higher incidence of rejection. 4. The impact of antibodies detected by FCXM on graft survival was strongest among retransplanted patients (60% 3-year graft survival with a positive FCXM vs 79% with a negative FCXM, p = 0.003), although significant differences were also noted in primary transplants (76% 3-year graft survival with a positive FCXM vs 81% with a negative FCXM, p < 0.001). Class I reactivity generally had a greater impact on survival, although class II antibodies had a deleterious effect as well. 5. Primary transplants across a T+B+ FCXM (n = 187) had a 76% 3-year graft survival rate compared with 74% for 509 T-B+ transplants. Both were significantly lower than the 81% 3-year graft survival rate for 5,017 T-B- FCXM transplants. 6. Retransplants across a T+B+ FCXM (n = 48) had a 60% 3-year regraft survival rate compared with 73% for 118 T-B+ regrafts and 79% when the FCXM was negative when tested against both targets (T-B-, n = 698). 7. Although there is room for improvement in the technique, the FCXM continues to be effective in identifying kidney transplants at risk of early graft failure and of rejection.

B-Lymphocytes↗