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Biomedical subjects

K O'Rourke

Publications and source records attributed to K O'Rourke.

123 records · Page 7Linked to original sources
PubMed1985

Inhibition of platelet aggregation by a monoclonal antibody against human fibronectin.

A monoclonal antibody (A3.3) has been generated against human platelet fibronectin (FN). A3.3 reacts with human plasma FN but with no other plasma proteins. A3.3 was found to inhibit thrombin- or ionophore A23187-stimulated aggregation of gel-filtered platelets in a concentration-dependent manner in both an aggregometer assay and a sensitive well plate aggregation assay. The antibody does not block secretion of serotonin. Four other anti-FN monoclonal antibodies that recognize different epitopes on FN than A3.3 does have no effect on platelet aggregation. A3.3 does not block the adhesion of CHO cells to FN-coated surfaces, indicating that it does not bind to the identified cell-binding domain of FN. A3.3 reacts with a 160/140-kDa doublet, known to contain the cell-binding domain, that is produced by digestion of FN with elastase or thermolysin. However, the antibody does not react with lower molecular weight species that also contain the cell-binding domain or with any of the other identified domains of FN. The A3.3 epitope is extremely protease sensitive and the smallest fragment found in any digest that retains reactivity with A3.3 is a 70-kDa peptide produced in low yield by mild thermolytic cleavage of FN. These data suggest that A3.3 defines a functional site present on both the platelet and plasma FN molecule that has a direct role in platelet aggregation.

Animals↗
PubMedDate not supplied

The hazards of using active clinic patients as a source of subjects for clinical studies.

The authors describe and empirically demonstrate a form of bias that results from deriving subjects for clinical studies from available patients currently being followed in specific disease clinics instead of inception cohorts (patients enrolled at a uniform and early point in their disease). They label this effect "clinic patient bias." It is a variation of prevalence-incidence (Neyman) bias in that it also results from the time gap between the onset of a specific characteristic (a risk factor, exposure or disease) and enrollment in the study, causing selective exclusion of fatal or short episodes, or mild or silent cases. Clinic patient bias may distort an estimate of relative risk in either direction. The empirical example is derived from a study of risk factors for developing complications such as peritonitis among end-stage renal disease patients treated with continuous ambulatory peritoneal dialysis (CAPD). The use of available clinic patients rather than an inception cohort (patients newly beginning CAPD) resulted in the demonstration of false apparent risk relationships for two variables: the calendar date when patients began CAPD (with those enrolled at an earlier time appearing to be at lower risk), and serum albumin level at the start of CAPD (with those having lower albumin levels appearing to be at higher risk). This example demonstrates one of the potential hazards of using active or available clinic patients as a source of subjects for clinical studies.

Cross-Sectional Studies↗
PubMedDate not supplied

Histologic estimation of coronary artery stenoses: reproducibility and the effect of training.

Histologic estimation of coronary artery stenoses (CAS) provides the 'gold-standard' for clinicopathologic correlations and medicolegal investigations, yet little evidence supports histology as a reproducible diagnostic measure, and none addresses the effect of training on its use. To study these questions, 20 randomly selected Movat-stained coronary artery cross-sections were reviewed 3 times, at 3-month intervals, by six clinical pathologists (CPs), six pathology residents (Res), seven anatomic pathologists (APs), and two cardiovascular pathologists (CVPs). Before the third iteration, a guide to CAS assessment with illustrations was provided. Inter- and intraobserver reproducibility were determined using interclass correlation coefficients (ICC) (0.40-0.75 = fair-good; > or = 0.76 = excellent agreement beyond chance). Surprisingly, all study groups had excellent interobserver reproducibility. Before training, at Time 1, the scores were CPs, 0.77; Res, 0.89; APs, 0.93; and CVPs, 0.93. After training, at Time 3, the results were CPs, 0.81; Res, 0.91; APs, 0.86; and CVPs, 0.88. Intraobserver reproducibility for CPs overall was good (ICC, 0.74), and excellent for Res, APs, and CVPs (0.89, 0.94, and 0.97, respectively). In conclusion, statistical analysis failed to demonstrate any significant effect of training or experience on observer reproducibility.

Autopsy↗
PubMedDate not supplied

The histologic estimation of coronary artery stenoses: accuracy and the effect of lumen shape.

The authors have recently investigated the histologic estimation of coronary artery stenoses (CAS) to determine its reproducibility and the effect of training on reproducibility. The present study extends this work, examining the accuracy, the sensitivity, and the specificity of the estimation of CAS. Further, the effect of one histologic variable (i.e., arterial lumen shape) on the evaluation of CAS is examined. As described previously, 20 randomly selected Movat-stained coronary artery cross-sections were reviewed three times, at 3-month intervals, by six clinical pathologists (CPs), six pathology residents (Res), seven anatomic pathologists (APs), and two cardiovascular pathologists (CVPs). Before the third iteration, training in CAS assessment was provided. In the present study, for comparison with observer estimates, image analysis was used to establish the actual percent CAS and determine observer accuracy. The results of this study showed, paradoxically, that greater experience did not correlate with greater accuracy: The CPs consistently had the highest accuracy scores and the CVPs consistently had the lowest. Training, however, improved the accuracy scores of all groups. Stenotic arterial cross-sections with residual lumens showing concentric or eccentric polymorphous shapes were consistently underestimated compared to image analysis, while lumens with a eccentric slitlike shape were consistently overestimated.

Arteries↗
PubMedDate not supplied

Predicting nutrition-associated complications for patients undergoing gastrointestinal surgery.

We studied 202 patients admitted to two major teaching hospitals for planned gastrointestinal surgery to assess the ability of several techniques of nutritional assessment to predict major postoperative complications (infection and/or wound problems). Subjective global assessment (SGA) and albumin were both of predictive value, and combinations of these variables were useful in differentiating low-risk from high-risk patients. Transferrin, creatinine-height index, percent ideal weight, percent body fat, and total lymphocyte count were not useful in predicting complications. We conclude that SGA and albumin are useful "nutritional assessment techniques" for patients undergoing major gastrointestinal surgery if the purpose of such an assessment is to predict postoperative "nutrition-associated complications." The second major finding of this study was the unexpectedly low rate of complications (10%) which was found in both hospitals. We suggest that these low complication rates may be more generalizable to patient populations derived from a wide community base, rather than those described in other studies in which veterans or patients of lower socioeconomic status comprised the sample.

Female↗
PubMedDate not supplied

Does treatment with essential amino acids and hypertonic glucose improve survival in acute renal failure?: A meta-analysis.

We performed a meta-analysis of four randomized trials (RCTs) and one concurrent control study which addressed the following question: Does treatment with amino acid solutions and hypertonic glucose improve survival of seriously ill patients with acute renal failure who are unable to take oral or enteral feedings? Three RCTs compared outcomes with essential amino acid solutions (EAA) and hypertonic glucose against hypertonic glucose alone, and their results were pooled. Use of EAA was associated with an absolute increase in initial survival of 0.24 as compared to glucose (confidence interval: +.015 to +.446). Without weighting the data to reflect the quality of the RCTs, this effect was significant (p = .017). Patients needing dialysis showed a significant treatment effect (p = .015), while those not requiring dialysis did not (p = .11). However, survival to hospital discharge was not significantly improved for the patient population as a whole (p = .10). Using a standardized quality assessment protocol, the four RCTs received scores ranging from .188 to .357 out of a possible 1.00. Any statistically significant treatment effects were abolished by factoring the quality scores of the studies into the data-pooling process. Sensitivity analysis was performed to determine the effect of including the nonrandomized study. Although it had more patients than the other studies combined, the nonrandomized study was of low quality (score: .032) and its inclusion did not change the outcome of data pooling once quality weighting was applied. We conclude that the efficacy of these parenteral nutritional regimens remains uncertain in this clinical setting.

Acute Kidney Injury↗
PubMedDate not supplied

Evolution of Church teaching on prolonging life.

God gave us the gift of human life to show forth his goodness and love. We, in turn, show our love for God by respecting and fostering that gift. Thus it is not an act of responsible human love to willfully and directly end one's own or the life of another. At times, however, the choice of another good may justify the indirect surrender of human life--for example, martyrs who surrender their lives rather than deny God. From the earliest centuries of the Church, the main questions concerning care for life as an act of love for God focused on suicide and euthanasia. But as the possibility of prolonging life through medicine or surgery increased, theologians started questioning how much effort should be expended to stay alive. The terms "ordinary means" and "extraordinary means" to prolong life were gradually introduced in Catholic teaching over the centuries. "Ordinary means" originally were those readily at hand and available to all; "extraordinary means" were expensive, difficult to obtain, or inconvenient to arrange for the average person. Over the years, they were used to signify whether particular means were morally obligatory (ordinary) or morally optional (extraordinary). Today the terms "proportionate-disproportionate" and "burden-benefit" have replaced "ordinary" and "extraordinary" to a great extent.(ABSTRACT TRUNCATED AT 250 WORDS)

Catholicism↗
PubMedDate not supplied

Video-EEG recording: a four-year clinical audit.

In the setting of a regional neurological unit without an epilepsy surgery service as in our case, video-EEG telemetry is undertaken for three main reasons; to investigate whether frequent paroxysmal events represent seizures when there is clinical doubt, to attempt anatomical localization of partial seizures when standard EEG is unhelpful, and to attempt to confirm that seizures are non-epileptic when this is suspected. A clinical audit of all telemetry performed over a four-year period was carried out, in order to determine the clinical utility of this aspect of the service and to determine means of improving effectiveness in the unit. Analysis of the data showed a high rate of negative studies with no attacks recorded. Of the positive studies approximately 50% showed non-epileptic attacks. Strategies for improving the rate of positive investigations are discussed.

Electroencephalography↗
PubMedDate not supplied

Parenteral nutrition in cancer patients undergoing chemotherapy: a meta-analysis.

Despite numerous controlled clinical trials, the indications for parenteral nutritional support of cancer patients undergoing chemotherapy remain controversial. The results of the published trials have therefore been subjected to meta-analysis. The pooled data show that total parenteral nutrition (TPN) has a detrimental effect: best estimates associate TPN use with trends to decreased survival (relative risk 0.81; 95% confidence limits [CL] 0.62, 1.0) and poorer tumor response (odds ratio 0.68; 95% CL 0.40, 1.1), with a significant increase in infectious complications (odds ratio 4.1; 95% CL 2.4, 6.9), and no clinically significant effect on gastrointestinal or hematologic toxicity (data not amenable to quantitative analysis). The increased risk of infection persists when catheter-related septicemia is excluded, suggesting that TPN itself may increase susceptibility to infection. In summary, for the patients in trials to date, TPN was associated with net harm. Routine use of TPN in patients undergoing chemotherapy should be strongly discouraged, and trials involving specific groups of patients or modifications in TPN should be undertaken with caution.

Antineoplastic Agents↗