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Biomedical subjects

D Cook

Publications and source records attributed to D Cook.

At least 37 records · Page 2Linked to original sources

The application of powdered activated carbon for MIB and geosmin removal: predicting PAC doses in four raw waters.

Blooms of blue-green algae in reservoirs often produce the musty-earthy taste and odour algal metabolites 2-methylisoborneol (MIB) and geosmin. MIB and geosmin are not removed by conventional water treatment and their presence in the distribution system, even at low ng L-1 levels, can result in consumer complaints. Powdered activated carbon (PAC) can effectively remove MIB and geosmin when the correct dose is applied. The homogeneous surface diffusion model (HSDM) was used to predict PAC doses required to reduce MIB and geosmin concentrations to below 10 ng L-1 at four water treatment plants in Adelaide, South Australia. In jar tests, undertaken under treatment plant conditions, the predicted doses were found to produce water of the desired quality in three of the four waters. The poor predictions found in the fourth water, which had a considerably higher turbidity, were attributed to the incorporation of PAC in a larger, denser floc, leading to a reduced effective contact time of the adsorbent. It was found that higher doses of PAC were required for both compounds to produce acceptable quality water when turbidities rose above 26 NTU.

Adsorption↗

Integration of the FISH pachytene and genetic maps of Medicago truncatula.

A molecular cytogenetic map of Medicago truncatula (2n = 2x = 16) was constructed on the basis of a pachytene DAPI karyogram. Chromosomes at this meiotic prophase stage are 20 times longer than at mitotic metaphase, and display a well differentiated pattern of brightly fluorescing heterochromatin segments. We describe here a pachytene karyogram in which all chromosomes can be identified based on chromosome length, centromere position, heterochromatin patterns, and the positions of three repetitive sequences (5S rDNA, 45S rDNA and the MtR1 tandem repeat), visualized by fluorescence in situ hybridization (FISH). We determined the correlation between genetic linkage groups and chromosomes by FISH mapping of bacterial artificial chromosome (BAC) clones, with two to five BACs per linkage group. In the cytogenetic map, chromosomes were numbered according to their corresponding linkage groups. We determined the relative positions of the 20 BACs and three repetitive sequences on the pachytene chromosomes, and compared the genetic and cytological distances between markers. The mapping resolution was determined in a euchromatic part of chromosome 5 by comparing the cytological distances between FISH signals of clones of a BAC contig with their corresponding physical distance, and showed that resolution in this region is about 60 kb. The establishment of this FISH pachytene karyotype, with a far better mapping resolution and detection sensitivity compared to those in the highly condensed mitotic metaphase complements, has created the basis for the integration of molecular, genetic and cytogenetic maps in M. truncatula.

Base Sequence↗

Gastrointestinal transit and anorectal manometry in children with colonic substance P deficiency.

BACKGROUND AND AIMS: Severe intractable constipation in children may be associated with a reduction of substance P (SP)- containing fibers in colonic circular muscle. The aim of this study was to characterize gastrointestinal transit (GIT), anorectal manometry (ARM) and electromyographic (EMG) changes in these children. METHODS: Seromuscular laparoscopic biopsies of the colon were obtained from 35 children with severe constipation. Immunofluorescent staining for SP and vasoactive intestinal peptide (VIP) were then performed on these specimens. The cohort of patients studied included a SP-deficient group (SPD, n = 25) who had reduced numbers of SP-immunoreactive nerve fibers. The other group consisted of patients with normal staining for both SP and VIP (SPN, n = 10). Gastrointestinal transit studies (gastric emptying, orocecal and colonic transit) suitable for analysis were available for 17 patients (SPD, n = 9 and SPN, n = 8). The colon was divided into segments and radioactivity counts in each segment were expressed as a percentage of the total colonic count at each time point (6, 24, 32 and 48 h). The geometric center (GC), ARM, EMG, clinical and demographic data characteristics of both groups of patients were compared. RESULTS: There were no differences in demographic data, gastric emptying, orocecal transit or geometric center of transit in the colon between the two patient groups. The ARM and EMG studies suggested that the SPN group have a higher mean threshold volume of balloon distension required to initiate a rectoanal inhibitory reflex, and a higher incidence of anismus; however, this did not reach statistical significance. CONCLUSIONS: These data suggest a trend that the SPN patients have a greater problem with obstructive defecation and abnormal rectal sensation than those with SPD. We were unable to confirm any defect in colonic transit in the SPD patients compared with the SPN group.

Anal Canal↗

Prevention of venous thromboembolism in critically ill surgery patients: a cross-sectional study.

BACKGROUND: The risk for venous thromboembolism (VTE) and the risk for bleeding among critically ill surgical patients are both important in the early postoperative period. MATERIALS AND METHODS: To record VTE prophylaxis prescribed for surgical patients in the intensive care unit (ICU) within the first postoperative week. We conducted a prospective observational cross-sectional study of Canadian university affiliated ICUs. RESULTS: Of 29 ICU Directors approached, 28 (96.6%) participated, representing 34 ICUs and 589 ICU beds across Canada. Among 89 patients, surgical procedures were 32 abdominal (36.0%), 19 vascular (21.3%), 10 orthopedic (11.2%), 9 trauma (10.1%), 8 neurologic (9.0%), 5 thoracic (5.6%), 5 gynecologic (5.6%), and 1 for necrotizing fasciitis (1.1%). VTE prophylaxis with unfractionated heparin, low molecular weight heparin, and intermittent pneumatic compression was used in 35 of 89 (39.3%), 8 of 89 (9.0%), and 9 of 89 (10.1%) patients, respectively, whereas 8 of 89 (9.0%) patients were receiving therapeutic anticoagulation. Two methods of VTE prophylaxis were prescribed for 20 of 89 (22.5%) patients. Prophylaxis with unfractionated or low molecular weight heparin was significantly less likely to be prescribed for postoperative ICU patients requiring mechanical ventilation compared with those weaned from mechanical ventilation (odds ratio [OR] 0.36, P =.03). The use of intermittent pneumatic compression devices was significantly associated with current hemorrhage (OR 13.5, P =.02), and risk for future hemorrhage (OR 19.3, P =.001). CONCLUSIONS: VTE prevention for surgical ICU patients within the first postoperative week appear to be individualized, and influenced by current and future risks of thrombosis and bleeding.

Adult↗

tiK+ toK+: an embryonic clock?

During embryogenesis cells make appropriately timed developmental decisions. Both 'hourglass-like' and 'clock-like' mechanisms have been demonstrated to act as timers in early development. The cell cycle rhythm, using feedback circuits to drive cells unidirectionally through checkpoints, is an example of a clock-like timer, but how it operates to time developmental events is unclear. In other cell types, cyclic oscillations in K+ channel activity, which parallel cell cycle and circadian rhythms, may be part of the timing mechanism. Changes in K+ oscillations accompany key developmental transitions and oncogenic transformation. Channel blockade interferes pharmacologically with cell cycle initiation or progression, whereas channel over-expression can be oncogenic. K+ channel activity also exists in early mouse oocytes through to at least the blastocyst stage, and it oscillates in phase with the developmental cell cycles, being high in M/G1 and low in S/G2. It resembles physiologically the activity of the K+ channels of the eag- or erg-like families. Reverse transcriptase-polymerase chain reaction of mouse oocytes has revealed the presence of transcripts encoding both EAG- and ERG-like proteins throughout preimplantation development. Channel activity continues to oscillate with a cell cycle periodicity in embryos from which the nucleus has been removed, or after inhibition by puromycin of the cyclin B-cyclin-dependent kinase 1 driven component of the chromosomal cycle. Channel oscillatory activity thus appears to be able to function autonomously of the chromosomal cycle and may represent a distinct oscillatory timing activity with possible developmental significance.

Animals↗

Patient autonomy versus parentalism.

Several decision-making models have been advanced to characterize the patient-physician relationship. These include the parental model, the informed decision-making model, the interpretive model, and the deliberative model. Although these models are useful to consider in reflecting on the care we give to critically ill patients at the end of life, they require adaptation to the intensive care unit (ICU). Many clinicians adapt their approach to each individual patient and change their approach to the same patient over time. Moreover, instead of the dyadic model of one patient and one physician, multiple voices often speak for the patient and a team of clinicians care for the ICU patient. Analysis of human relationships and communication with critically ill patients and their families require transdisciplinary, multicultural, and multidisciplinary interpretation.

Authoritarianism↗

New strategies for clinical trials in patients with sepsis and septic shock.

OBJECTIVE: The difficulty in identifying new treatment modalities that significantly reduce the mortality and morbidity rates associated with sepsis has highlighted the need to reevaluate the approach to clinical trial design. The United Kingdom Medical Research Council convened an International Working Party to address these issues. DATA SOURCES: The subject areas that were to be the focus of discussion were identified by the co-chairs, and group leaders were nominated. Preconference reading material was circulated to group members. STUDY SELECTION AND DATA EXTRACTION: Small-group discussion fed into an iterative process of feedback from plenary sessions, followed by the formulation of recommendations. Finally, each working group prepared a summary of its recommendations and these are reported herein. DATA SYNTHESIS: There were five key recommendations. First, investigators should no longer rely solely on the American College of Chest Physicians/Society of Critical Care Medicine definitions of sepsis or sepsis syndrome as the basis of trial entry. Entry criteria should be based on three principles: a) All patients should have infection; b) there should be evidence of a pathologic process that represents a biologically plausible target for the proposed intervention, for example, an abnormal circulating level of a biological marker pertinent to the study drug; and c) patients should fall into an appropriate category of severity (usually severe sepsis). Second, investigators should use a scoring system for organ dysfunctions that has been validated and that can be incorporated into all sepsis studies; agreement on the use of a single system would simplify comparisons between studies. Third, the primary outcome measure generally should be mortality rates, but under appropriate circumstances major morbidities could be considered as primary end points. Regardless of choice of the duration to primary end point, patients should be followed for > or =90 days. Fourth, sample size needs to be based on a realistic assessment of achievable effect size based on knowledge of the at-risk population. Fifth, subgroups should be few in number and should be defined a priori on the basis of variables present before randomization. CONCLUSIONS: Important changes in several aspects of trial design may improve the quality of clinical studies in sepsis and maximize the chance of identifying effective therapeutic agents.

Clinical Trials as Topic↗

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↗

School-based telehealth: an empirical analysis of teacher, nurse, and administrator perceptions.

In 1997, the University of Kansas Medical Center (KUMC) and the United School District 500 (USD 500) in Kansas City, Kansas, launched an innovative telehealth project that brought health care directly into elementary schools by interactive video technology and peripheral devices. This paper focuses on the attitudes and opinions of key players--teachers, nurses, and administrators--involved in providing the service. Research methodology involved analyzing archival data and conducting interviews with key players on the project from USD 500 and KUMC. The study highlights the difficulty in delivering health care, especially telehealth care, to underserved, urban children. The data also reveal that initial challenges and negative attitudes can be overcome to effectively deliver telehealth care in the school setting.

Administrative Personnel↗

Regular versus as-needed short-acting inhaled beta-agonist therapy for chronic obstructive pulmonary disease.

Regular short-acting inhaled beta-agonist therapy is of uncertain benefit in patients with chronic obstructive pulmonary disease (COPD). We conducted a randomized, concealed, double-blind, placebo-controlled crossover trial in two periods, each of 3-mo duration, involving 53 patients with a smoking history of > 20 pack-years, an FEV1 of < 70% predicted, and an FEV1/VC ratio of < 0.7 after inhalation of 200 microg albuterol. All patients received regular ipratropium bromide at 20 microg per puff in 2 puffs four times daily, beclomethasone at 250 microg per puff or equivalent corticosteroid in 2 puffs twice daily, and open-label inhaled albuterol as needed. Interventional therapy consisted of regular inhaled albuterol (100 microg per puff, in 2 puffs four times daily) versus placebo. Patients used twice as much active albuterol in the regular use period (mean: 8.07 puffs of coded and 4.68 puffs of open-label medication; total: 12.75 puffs daily) than during the as-needed period (mean: 6.34 puffs of open-label albuterol daily). Despite greater beta-agonist use, patients showed similar results during treatment and control periods for all outcomes. Differences between active and placebo periods were: FEV1: -0.04 L (95% confidence interval [CI]: -0.09 to 0.01 L); slow vital capacity: 0.04 L (95% CI: -0.12 to 0.20 L); 6-min walk test distance: -3.1 m (95% CI: -16.8 to 10.5 m); and Chronic Respiratory Questionnaire scores for dyspnea: 0.02 (95% CI: -0.13 to 0.16); fatigue: -0.02 (95% CI: -0.25 to 0.20); mastery: 0.01 (95% CI: -0.20 to 0.24); and emotional function: 0.02 (95% CI: -0.20 to 0.24). We found that in patients with COPD, use of regular short-acting inhaled beta-agonists resulted in twice as much beta-agonist use without physiologic or clinical benefit as did use on an as-needed basis.

Administration, Inhalation↗

The HCL gene of Medicago truncatula controls Rhizobium-induced root hair curling.

The symbiotic infection of the model legume Medicago truncatula by Sinorhizobium meliloti involves marked root hair curling, a stage where entrapment of the microsymbiont occurs in a chamber from which infection thread formation is initiated within the root hair. We have genetically dissected these early symbiotic interactions using both plant and rhizobial mutants and have identified a M. truncatula gene, HCL, which controls root hair curling. S. meliloti Nod factors, which are required for the infection process, induced wild-type epidermal nodulin gene expression and root hair deformation in hcl mutants, while Nod factor induction of cortical cell division foci was reduced compared to wild-type plants. Studies of the position of nuclei and of the microtubule cytoskeleton network of hcl mutants revealed that root hair, as well as cortical cells, were activated in response to S. meliloti. However, the asymmetric microtubule network that is typical of curled root hairs, did not form in the mutants, and activated cortical cells did not become polarised and did not exhibit the microtubular cytoplasmic bridges characteristic of the pre-infection threads induced by rhizobia in M. truncatula. These data suggest that hcl mutations alter the formation of signalling centres that normally provide positional information for the reorganisation of the microtubular cytoskeleton in epidermal and cortical cells.

Acetyltransferases↗

Grades of recommendation for antithrombotic agents.

The strength of any recommendation depends on two factors: the trade-off between benefits and risks, and the strength of the methodology that leads us to estimates of the treatment effect. The framework that we used for this conference captures these factors. We grade the trade-off between benefits and risks in two categories: (1) the trade-off is clear enough that most patients, despite differences in values, would make the same choice; and (2) the trade-off is less clear, and each patient's values will likely lead to different choices. We grade methodologic strength in three categories: (1) randomized trials, ideally summarized in a meta-analysis, that show consistent results; (2) randomized trials with inconsistent results; and (3)observational studies. The framework summarized in Table 1 therefore generates recommendations from the very strong (1A: benefit/risk clear, methods strong) to the very weak (2C: benefit/risk questionable, methods weak). Whatever the grade of recommendation, clinicians must bring their judgment considering local and individual patient circumstances, and patient values, to bear in making individual decisions. In general, however, they should place progressively greater weight on expert recommendations as they move from 2C to 1A.

Fibrinolytic Agents↗

Predicting success in weaning from mechanical ventilation.

We identified 65 observational studies of weaning predictors that had been reported in 70 publications. After grouping predictors with similar names but different thresholds, the following predictors met our relevance criteria: heterogeneous populations, 51; COPD patients, 21; and cardiovascular ICU patients, 45. Many variables were of no use in predicting the results of weaning. Moreover, few variables had been studied in > 50 patients or had results presented to generate estimates of predictive power. For stepwise reductions in mechanical support, the most promising predictors were a rapid shallow breathing index (RSBI) < 65 breaths/min/L (measured using the ventilator settings that were in effect at the time that the prediction was made) and a pressure time product < 275 cm H2O/L/s. The pooled likelihood ratios (LRs) were 1.1 (95% confidence interval [CI], 0.95 to 1.28) for a respiratory rate [RR] of < 38 breaths/min and 0.32 (95% CI, 0.06 to 1.71) for an RR of > 38 breaths/min, which indicate that an RR of < 38 breaths/min leaves the probability of successful weaning virtually unchanged but that a value of > 38 breaths/min leads to a small reduction in the probability of success in weaning the level of mechanical support. For trials of unassisted breathing, the most promising weaning predictors include the following: RR; RSBI; a product of RSBI and occlusion pressure < 450 cm H2O breaths/min/L; maximal inspiratory pressure (PImax) < 20 cm H2O; and a knowledge-based system for adjusting pressure support. Pooled results for the power of a positive test result for both RR and RSBI were limited (highest LR, 2.23), while the power of a negative test result was substantial (ie, LR, 0.09 to 0.23). Summary data suggest a similar predictive power for RR and RSBI. In the prediction of successful extubation, an RR of < 38 breaths/min (sensitivity, 88%; specificity, 47%), an RSBI < 100 or 105 breaths/min/L (sensitivity, 65 to 96%; specificity, 0 to 73%), PImax, and APACHE (acute physiology and chronic health evaluation) II scores that are obtained at hospital admission appear to be the most promising. After pooling, two variables appeared to have some value. An RR of > 38 breaths/min and an RSBI of > 100 breaths/min/L appear to reduce the probability of successful extubation, and PImax < 0.3, for which the pooled LR is 2.23 (95% CI, 1.15 to 4.34), appears to marginally increase the likelihood of successful extubation. Judging by areas under the receiver operator curve for all variables, none of these variables demonstrate more than modest accuracy in predicting weaning outcome. Why do most of these tests perform so poorly? The likely explanation is that clinicians have already considered the results when they choose patients for trials of weaning.

APACHE↗

Trials of miscellaneous interventions to wean from mechanical ventilation.

We found eight randomized controlled trials (RCTs) of miscellaneous interventions that were designed to facilitate the process of weaning from mechanical ventilation. The two RCTs of high-fat/low-carbohydrate enteral nutrition found favorable physiologic effects on CO2 production and respiratory quotient, rendering this type of nutrition potentially useful in patients with impaired ventilatory reserve; however, no conclusions can be made about the outcomes of the duration of ventilation and weaning success. The two RCTs of postextubation use of noninvasive ventilation are conflicting, showing potential short-term physiologic benefit in one study, but no benefit in terms of reintubation rates or other morbidity. These RCTs are less promising than other applications of noninvasive ventilation such as those in patients with COPD exacerbations. One RCT showed no improvement in success of weaning with exogenous growth hormone administration. In the setting of very frequent baseline blood gas analyses, one RCT of oximetry and capnography was associated with significantly fewer blood gas analyses. Biofeedback to enhance safe and rapid weaning showed a dramatically lower duration of ventilation in one RCT that did not report the weaning methods used. One RCT of preextubation acupuncture showed lower rates of laryngospasm in the acupuncture group. Overall, these studies were underpowered for clinically important outcomes. Multidisciplinary, patient-centered, holistic, and non-pulmonary approaches to weaning may provide additional safe, effective adjunctive methods of hastening liberation from mechanical ventilation.

Acupuncture↗