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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
PubMed1997

Current guidelines on stress ulcer prophylaxis.

Acute uppergastrointestinal bleeding in intensive care unit (ICU) patients may occur due to peptic ulcer disease, adverse drug effects, gastric tube lesions, acute renal failure, liver failure or stress-induced gastric mucosal lesions. Gastric acid hypersecretion can be observed in patients with head trauma or neurosurgical procedures. Gastric mucosal ischaemia due to hypotension and shock is the most important risk factor for stress ulcer bleeding. Preventive strategies aim to reduce gastric acidity (histamine H2 receptor antagonists, antacids), strengthen mucosal defensive mechanisms (sucralfate, antacids, pirenzepine) and normalise gastric mucosal microcirculation (sucralfate, pirenzepine). However, the most important prophylactic measure is an optimised resuscitation and ICU regime aiming to improve oxygenation and microcirculation. All drugs approved for stress ulcer prophylaxis in Europe (H2 antagonists, antacids, pirenzepine, sucralfate) have been shown to be effective in prospective controlled randomised trials. However, due to insufficient clinical data, prostaglandins and omeprazole cannot be recommended for this use. Stress ulcer prophylaxis is indicated only in patients at risk, and not in every ICU patient. The selection of drugs today depends not only on efficacy but also on possible adverse effects and on costs. In this regard, the most cost-effective drug is sucralfate. The clinical relevance of nosocomial pneumonia due to gastric bacterial overgrowth has decreased during the past decade due to several changes in the management of critically ill patients.

Antacids↗
PubMed1996

Wingless inactivates glycogen synthase kinase-3 via an intracellular signalling pathway which involves a protein kinase C.

The Drosophila gene product Wingless (Wg) is a secreted glycoprotein and a member of the Wnt gene family. Genetic analysis of Drosophila epidermal development has defined a putative paracrine Wg signalling pathway involving the zeste-white 3/shaggy (zw3/sgg) gene product. Although putative components of Wg- (and by inference Wnt-) mediated signalling pathways have been identified by genetic analysis, the biochemical significance of most factors remains unproven. Here we show that in mouse 10T1/2 fibroblasts the activity of glycogen synthase kinase-3 (GSK-3), the murine homologue of Zw3/Sgg, is inactivated by Wg. This occurs through a signalling pathway that is distinct from insulin-mediated regulation of GSK-3 in that Wg signalling to GSK-3 is insensitive to wortmannin. Additionally, Wg-induced inactivation of GSK-3 is sensitive to both the protein kinase C (PKC) inhibitor Ro31-8220 and prolonged pre-treatment of 10T1/2 fibroblasts with phorbol ester. These findings provide the first biochemical evidence in support of the genetically defined pathway from Wg to Zw3/Sgg, and suggest a previously uncharacterized role for a PKC upstream of GSK-3/Zw3 during Wnt/Wg signal transduction.

Androstadienes↗
PubMed1996

Aerosol deposition in infants with cystic fibrosis.

Twenty asymptomatic infants with cystic fibrosis (CF) were studied to determine the amount of radiolabeled aerosol [99m technetium diethylenetriamine penta acetic acid (Tc99m DTPA)] deposited in the respiratory system and its distribution. Aerosols were generated by jet nebulization systems that were used in the wards and the laboratory. Subjects were studied in three groups: group A (n = 10) was sedated with chloral hydrate; children inhaled an aerosol of 7.7 microns mass median diameter (MMD); group B (n = 5) was not sedated, using the same nebulization system (same aerosol particle size as group A); and group C (n = 5) was not sedated; these children inhaled an aerosol with an MMD of 3.6 microns. Normal saline plus 4 mCi of Tc99m bound to DTPA was added to each nebulizer. A closed system was used to collect the expired aerosol. Radioactivity in each infant and in the equipment was measured with a gamma camera on completion of nebulization. In groups A and B, the percentages of the total dose deposited in the lung were 0.97 +/- 0.35% and 0.76 +/- 0.36%, respectively. In group C, 2.0 +/- 0.71% was deposited in the lung (P < 0.01). Deposition in the nose, mouth, and pharynx was least in group C (P < 0.01). In groups A and B, the intrathoracic deposition occurred predominantly in the trachea and main bronchi, whereas in group C, significantly more aerosol was deposited in the lung region. There was marked inter-subject variability in the percentage of aerosol deposition within the three groups. There was no correlation between percentage of aerosol deposited in the respiratory system and age, height, or weight. Sedation did not have a significant effect on deposition of aerosol in infants. This study indicates that only a small proportion of nebulized solution is deposited in the lungs of infants and that this proportion is influenced by the particle size of the aerosol. The smaller particle size (3.6 microns MMD) was deposited in the lung better than large particles.

Aerosols↗
PubMed1996

Does treatment with L-thyroxine influence health status in middle-aged and older adults with subclinical hypothyroidism?

OBJECTIVE: To determine if health-related quality of life (HRQL) in patients of middle age and older with elevated thyroid-stimulating hormone (TSH) and normal total thyroid hormone levels-subclinical hypothyroidism-improves with L-thyroxine replacement therapy. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Outpatient clinic. PATIENTS: Thirty-seven patients with subclinical hypothyroidism, most with symptoms consistent with hypothyroidism, over 55 years of age. INTERVENTIONS: Placebo or L-thyroxine replacement therapy to achieve normal TSH level. MEASUREMENTS AND MAIN RESULTS: Disease-specific and general HRQL, cognitive function, bone mineral density, lipid levels. The mean daily dose of L-thyroxine replacement in the active group was 68 +/- 21 micrograms. TSH decreased by 8.6 mIU/L (95% confidence interval [CI] 4.1 to 13.1) and T4 increased by 27.9 nmol/L (95% CI 14.8 to 41.2). There was a statistically significant improvement in a composite psychometric memory score in treated versus control patients; all other outcomes showed similar findings in the two groups. Although confidence intervals for most measures did not exclude an important improvement in HRQL with thyroid replacement, no measure of symptoms or HRQL either showed clinically important trends in favor of treatment, or approached conventional levels of statistical significance. CONCLUSIONS: In middle-aged and older patients with elevated TSH and normal T4, it may not be harmful to follow biochemical and clinical status even in the presence of nonspecific symptoms potentially associated with hypothyroidism.

Aged↗
PubMed1996

Does volume of clinical experience affect performance of clinical clerks on surgery exit examinations?

BACKGROUND: Controversy persists over the educational value of student clerkship clinical activities. METHODS: Students (109) from the class of 1995 recorded their clinical experiences in a logbook during their surgical clerkship at one of four affiliated teaching hospitals. The influence of clinical experience on examination scores and on correlations between prerotation and postrotation examination performance was determined. RESULTS: Between sites, marked variation in clinical experience was observed but postrotation scores were similar. High-volume experience in emergency admissions and feedback was associated with better objective structured clinical examination (OSCE) performance, but high-volume outpatient clinic experience was associated with less satisfactory OSCE performance. Correlations between prerotation examination performance and the OSCE was increased by feedback on emergency and elective admissions, in a positive and negative direction, respectively. CONCLUSIONS: These data show that surgical clerks' clinical skills were enhanced by an increased volume of some but not all clinical experiences and that feedback does not necessarily enhance performance. These data suggest that both the volume of clinical experience and the quality of feedback should be carefully monitored by surgical clerkship directors.

Alberta↗
PubMed1996

Cadaveric kidney transplantation under prophylactic polyclonal antibody immunosuppression with anti-lymphoblast globulin versus anti-thymocyte globulin.

OBJECTIVES: This retrospective study was undertaken to evaluate and compare the clinical and immunologic outcomes following prophylactic induction treatment with Minnesota anti-lymphoblast globulin (MALG) and Upjohn anti-thymocyte globulin (ATGAM) in cadaver renal transplantation. METHODS: From 1990 to 1994, 63 patients with renal transplants from cadavers received MALG and 77 patients received ATGAM for induction treatment. Most pretransplant parameters were equivalent in both groups. There was no significant difference in the total dose and mean duration of MALG/ATGAM administration. The post-transplant outcome in these groups was compared. RESULTS: There was no difference between the MALG and ATGAM groups with respect to the overall number of rejection episodes, median days to rejection, or the number of steroid-resistant rejection episodes. However, MALG-treated patients experienced a greater number of rejections in the first 60 days postoperatively (P = 0.06). There was no difference in the nadir serum creatinine level in the first 20 postoperative days in the two groups; however, it took fewer days to reach the nadir in the ATGAM group (P = 0.03). The incidence of delayed graft function was higher in the MALG group than in the ATGAM group (38% versus 31%) but not statistically significant. Graft survival at 12 and 24 months was comparable in both groups. However, patient survival was superior at 12 and 24 months in ATGAM-treated transplant recipients (P = 0.03). The mean serum creatinine at 6, 12, and 24 months was similar in both the MALG and ATGAM groups. The mean fall and recovery of CD3, CD4, and CD8 T-lymphocyte subsets while on MALG/ATGAM were similar in both groups. The incidence of infectious complications was greater in the MALG group. CONCLUSIONS: MALG and ATGAM have comparable clinical immunosuppressive effects. Patients receiving ATGAM experienced fewer rejections in the first 2 months, fewer infections, and better survival.

Antilymphocyte Serum↗
PubMed1996

Gene structure and differential regulation of the Rhizobium-induced peroxidase gene rip1.

Primary expression of the Rhizobium meliloti-induced peroxidase gene rip1 occurs prior to nodule morphogenesis, specifically at the site of impending rhizobial infection (D. Cook, D. Dreyer, D. Bonnet, M. Howell, E. Nony, K. VandenBosch [1995] Plant Cell 7: 43-55). We examined the distribution and structure of rip1 transcript throughout nodule development. We determined that expression of rip1 in root tips is correlated with the competence of this zone for symbiotic association, whereas after rhizobial infection rip1 transcript is specifically associated with the zone of nodule development, including nascent nodule primordia. rip1 transcripts are characterized by multiple polyadenylation sites distributed within 200 to 400 bp of the translation stop site, and a single major transcription initiation site in close proximity to the rip1 open reading frame. Thus, rip1 expression is likely to be mediated through effects on a single transcription unit. Immediately 5' of the rip1 transcription unit DNA sequence analysis identified a 377-bp DNA element containing extensive repeat structure that is widely distributed in the Medicago truncatula genome.

Base Sequence↗
PubMed1996

Targeting gamma interferon to tumor cells by a genetically engineered fusion protein secreted from myeloma cells.

The construction, synthesis and expression of a genetically engineered bifunctional antibody/cytokine fusion protein is described. To target IFN-tau to tumor cells, recombinant antibody techniques were used to construct a RM4/IFN-tau fusion protein containing the chimeric anti-tumor F(ab')2 (RM4) and the IFN-tau moiety. The recombinant cDNA of IFN-tau was linked to 3 prime end of the chimeric heavy-chain gene fragment (M4) containing the VH, the CH1 and the hinge region to form the fused heavy-chain gene fragment M4-IFN-tau. Transfection of the M4-IFN-tau gene fragment into a myeloma derived cell line VKCK which produced the chimeric light-chain of the same antibody, allowed the transfectant secreting the bifunctional fusion protein RM4/IFN-tau. The RM4/IFN-tau was purified by the affinity chromatography. Our data showed that the RM4/IFN-tau retained the TAG72 antigen-binding reactivity as well as the IFN-tau activity as measured in ELISA, FACS analysis of cell-surface TAG72 expression, immunohistochemical study, and up-regulation of cell-surface expression of CEA, HLA class I and class II antigens. Therefore, the bifunctional fusion protein RM4/IFN-tau may prove to be useful in targeting biological effects of the IFN-tau to tumor cells and in this way to stimulate the immune destruction of tumor cells.

Adenocarcinoma↗
PubMed1995

Birth weight and blood pressure: cross sectional and longitudinal relations in childhood.

OBJECTIVE: To examine cross sectional and longitudinal relations between birth weight and blood pressure in childhood. DESIGN: Cross sectional study of primary school children aged 9-11 years, with analysis in relation to previous measurements at 5-7 years in a subgroup. SETTING: 20 primary schools in Guildford and Carlisle. SUBJECTS: 1511 children measured at 9-11 years (response rate 79%), including 549 who had been measured at 5-7 years. MAIN OUTCOME MEASURES: Blood pressure at 9-11 years, change in blood pressure between 5-7 and 9-11 years, birth weight (based on maternal recall), and placental weight (based on birth records). RESULTS: At 9-11 years birth weight was inversely related both to systolic blood pressure (regression coefficient -2.80 mm Hg/kg; 95% confidence interval -3.84 to -1.76) and to diastolic blood pressure (regression coefficient -1.42 mm Hg/kg; -2.14 to -0.70) once current height and body mass index were taken into account. Placental weight was inversely related to blood pressure after adjustment for current height and body mass index but placental ratio (placental weight to birth weight) was unrelated to blood pressure. Between 5-7 and 9-11 years systolic blood pressure rose more rapidly in children of lower birth weight (regression coefficient -1.71 mm Hg/kg; -3.35 to -0.07). This effect seemed to be stronger in girls. CONCLUSIONS: Birth weight rather than placental ratio is the early life factor most importantly related to blood pressure in childhood. The results support the possibility of "amplification" of the relation between birth weight and blood pressure, particularly in girls.

Aging↗
PubMed1995

Endoscopic ligation compared with sclerotherapy for treatment of esophageal variceal bleeding. A meta-analysis.

PURPOSE: To compare the effect of endoscopic ligation with that of sclerotherapy in the treatment of patients with bleeding esophageal varices. DATA SOURCES: Strategies to identify published and unpublished research included searches of computerized bibliographic and scientific citations, review of citations in relevant primary articles, searches of services providing information on unpublished studies, contact with primary investigators and the ligation equipment manufacturer, and review of proceedings from pertinent scientific meetings. STUDY SELECTION: From 158 potentially relevant articles, duplicate independent review identified 7 relevant randomized trials that compared endoscopic ligation with sclerotherapy for the treatment of patients with bleeding esophageal varices. DATA ABSTRACTION: Independent, duplicate data abstraction of the population, intervention, outcome, and methodologic quality of the trials was done. DATA SYNTHESIS: Ligation therapy compared with sclerotherapy reduced the rebleeding rate (odds ratio, 0.52 [95% CI, 0.37 to 0.74]), the mortality rate (odds ratio, 0.67 [CI, 0.46 to 0.98]), and the rate of death due to bleeding (odds ratio, 0.49 [CI, 0.24 to 0.996]). Four patients would need to be treated with ligation instead of sclerotherapy to avert one rebleeding episode, and 10 would need to be treated with ligation instead of sclerotherapy to prevent one death. Esophageal strictures occurred less frequently with ligation (odds ratio, 0.10 [CI, 0.03 to 0.29]), but no significant differences were seen between treatments for pulmonary infections or bacterial peritonitis. Additionally, the number of endoscopic treatment sessions required to achieve variceal obliteration was lower with ligation than with sclerotherapy. CONCLUSIONS: On the basis of lower rates of rebleeding, mortality, and complications and the need for fewer endoscopic treatments, ligation should be considered the endoscopic treatment of choice for patients with esophageal variceal bleeding.

Cause of Death↗
PubMed1995

Accuracy of a saliva test for HIV antibody.

The accuracy of a saliva collection and testing protocol for determination of HIV-1 antibody status was assessed under realistic field conditions. The 1,256 study participants came from two lower-prevalence settings--a self-referral testing clinic (478) and a street-based outreach program (431)--and two high-prevalence clinics--an HIV/AIDS treatment clinic (337) and a hemophilia clinic (10). Saliva was collected using the Omni-Sal collection device and was tested by technicians blind to serum status using a modified protocol that employed the Recombigen HIV-1 EIA. Serum was tested using standard methods. A single saliva enzyme immunoassay (EIA) correctly identified 358 of 368 seropositive individuals, for a sensitivity of 97.3% (95% CI: 95.1%-98.7), and 888 of 888 seronegative individuals, for a specificity of 100% (95% CI: 99.6-100). Confirmation of saliva EIA positives with a repeat saliva EIA and an in-house saliva radioimmunoprecipitation assay resulted in a substantial drop in sensitivity to 85.3% (95% CI: 81.0-89.0). We conclude that a single saliva EIA using the modified test protocol described is sufficiently accurate for surveillance purposes, but we do not recommend it for diagnostic purposes or screening.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Basic statistics for clinicians: 4. Correlation and regression.

Correlation and regression help us to understand the relation between variables and to predict patients' status in regard to a particular variable of interest. Correlation examines the strength of the relation between two variables, neither of which is considered the variable one is trying to predict (the target variable). Regression analysis examines the ability of one or more factors, called independent variables, to predict a patient's status in regard to the target or dependent variable. Independent and dependent variables may be continuous (taking a wide range of values) or binary (dichotomous, yielding yes-or-no results). Regression models can be used to construct clinical prediction rules that help to guide clinical decisions. In considering regression and correlation, clinicians should pay more attention to the magnitude of the correlation or the predictive power of the regression than to whether the relation is statistically significant.

Data Interpretation, Statistical↗
PubMed1995

Basic statistics for clinicians: 3. Assessing the effects of treatment: measures of association.

In the third of a series of four articles the authors show the calculation of measures of association and discuss their usefulness in clinical decision making. From the rates of death or other "events" in experimental and control groups in a clinical trial, we can calculate the relative risk (RR) of the event after the experimental treatment, expressed as a percentage of the risk without such treatment. The absolute risk reduction (ARR) is the difference in the risk of an event between the groups. The relative risk reduction is the percentage of the baseline risk (the risk of an event in the control patients) removed as a result of therapy. The odds ratio (OR), which is the measure of choice in case-control studies, gives the ratio of the odds of an event in the experimental group to those in the control group. The OR and the RR provide limited information in reporting the results of prospective trials because they do not reflect changes in the baseline risk. The ARR and the number needed to treat, which tells the clinician how many patients need to be treated to prevent one event, reflect both the baseline risk and the relative risk reduction. If the timing of events is important--to determine whether treatment extends life, for example--survival curves are used to show when events occur over time.

Case-Control Studies↗
PubMed1995

Basic statistics for clinicians: 2. Interpreting study results: confidence intervals.

In the second of four articles, the authors discuss the "estimation" approach to interpreting study results. Whereas, in hypothesis testing, study results lead the reader to reject or accept a null hypothesis, in estimation the reader can assess whether a result is strong or weak, definitive or not. A confidence interval, based on the observed result and the size of the sample, is calculated. It provides a range of probabilities within which the true probability would lie 95% or 90% of the time, depending on the precision desired. It also provides a way of determining whether the sample is large enough to make the trial definitive. If the lower boundary of a confidence interval is above the threshold considered clinically significant, then the trial is positive and definitive, if the lower boundary is somewhat below the threshold, the trial is positive, but studies with larger samples are needed. Similarly, if the upper boundary of a confidence interval is below the threshold considered significant, the trial is negative and definitive. However, a negative result with a confidence interval that crosses the threshold means that trials with larger samples are needed to make a definitive determination of clinical importance.

Clinical Trials as Topic↗
PubMed1995

Basic statistics for clinicians: 1. Hypothesis testing.

In the first of a series of four articles the authors explain the statistical concepts of hypothesis testing and p values. In many clinical trials investigators test a null hypothesis that there is no difference between a new treatment and a placebo or between two treatments. The result of a single experiment will almost always show some difference between the experimental and the control groups. Is the difference due to chance, or is it large enough to reject the null hypothesis and conclude that there is a true difference in treatment effects? Statistical tests yield a p value: the probability that the experiment would show a difference as great or greater than that observed if the null hypothesis were true. By convention, p values of less than 0.05 are considered statistically significant, and investigators conclude that there is a real difference. However, the smaller the sample size, the greater the chance of erroneously concluding that the experimental treatment does not differ from the control--in statistical terms, the power of the test may be inadequate. Tests of several outcomes from one set of data may lead to an erroneous conclusion that an outcome is significant if the joint probability of the outcomes is not taken into account. Hypothesis testing has limitations, which will be discussed in the next article in the series.

Clinical Trials as Topic↗