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Biomedical subjects

K O'Rourke

Publications and source records attributed to K O'Rourke.

At least 91 records · Page 5Linked to original sources
PubMed1995

[Evaluation of a training program for traditional birth attendants in Quetzaltenango, Guatemala].

In 1992, a training program for traditional birth attendants (TBAs) was initiated in Quetzaltenango, Guatemala, in order to improve the identification and treatment of neonatal disorders and high-risk pregnancies. This program was evaluated by comparing the pattern of hospital referrals by TBAs before and after the training. The study design consisted of a community intervention evaluated by means of several cross-sectional surveys. Comparisons were made between a group of TBAs who had received the training (intervention group) and another group of TBAs from nearby communities who had not received the training (control group). The outcome variables included the TBAs' ability to correctly identify obstetric complications, the point in time at which they sent mothers to the hospital, and perinatal mortality among the children whose mothers were referred to the hospital. Of the 854 women eligible, 845 participated in the study. Following the training program, there was a 200% increase in the number of mothers referred to the hospital by the TBAs. There was also improvement in the ability of the TBAs in the intervention group to refer women with obstetric complications to the hospital, although the effect of the program appeared to have been minimal on both that ability and the reduction of perinatal mortality. Nevertheless, the latter effect should be more precisely determined, since a decrease in perinatal mortality was observed in both the intervention and control groups, with no statistically significant difference.

Adolescent↗
PubMed1994

A novel RING finger protein interacts with the cytoplasmic domain of CD40.

CD40 is a member of the tumor necrosis factor receptor family and, like other members, it appears to possess no intrinsic signaling capacity (e.g. kinase activity), suggesting that signal transduction is likely mediated by associating molecules. To identify such molecules, we have utilized the yeast two-hybrid system to clone cDNAs encoding proteins that bind the CD40 cytoplasmic domain. One such interacting protein, designated CD40-binding protein, has a N-terminal RING finger motif that is found in a number of DNA-binding proteins, including the V(D)J recombination activating gene RAG1. In addition, it contains a prominent central coiled-coil segment that may allow homo- or hetero-oligomerization. The C terminus possesses substantial homology to the tumor necrosis factor receptor-associated factor (TRAF) domain that is found in two proteins (TRAF1 and TRAF2) that associate with the cytoplasmic domain of the related 75-kDa tumor necrosis factor receptor. This is the first identification of a molecule that interacts with CD40 and whose sequence suggests a potential role in signaling.

Amino Acid Sequence↗
PubMed1994

Lymphocyte function-associated antigen 1 overexpression and T cell autoreactivity.

OBJECTIVE: To determine if DNA methylation inhibitors make T cells autoreactive by inducing lymphocyte function-associated antigen type 1 (LFA-1) (CD11a/CD18) overexpression. METHODS: T cell clones were treated with 3 distinct DNA methylation inhibitors or were stably transfected with a CD18 cDNA in a mammalian expression vector, and the effects on LFA-1 expression and activation requirements were examined. RESULTS: LFA-1 overexpression, caused by DNA methylation inhibitors or by transfection, correlates with the development of autoreactivity. CONCLUSION: LFA-1 overexpression may contribute to T cell autoreactivity.

Azacitidine↗
PubMed1994

A randomized crossover trial of Quick Medical Reference (QMR) as a teaching tool for medical interns.

OBJECTIVE: To determine whether the addition of Quick Medical Reference (QMR) to usual educational tools improves an intern's performance in managing clinical cases that test diagnostic and investigative skills. DESIGN: Randomized, controlled, single-blinded crossover study. SETTING: Tertiary care teaching hospital. SUBJECTS: Comprehensive medical interns who are proficient in the use of QMR. INTERVENTION: A total of 16 interns trained in the use of QMR were randomized to work up a total of six diagnostically challenging cases, three using medical textbooks plus access to QMR and three using textbooks and no access to QMR. MEASUREMENTS: The interns provided their solutions to the cases, which consisted of the differential diagnosis and investigations. They were scored by comparing their answers with the consensus answers provided by subspecialty consultants. For each intern, the difference in mean total scores with and without QMR was calculated. RESULTS: The mean difference in total scores was 7.2% benefit (p < 0.05, 95% CI = 0.05 to 14.4) using QMR. The beneficial difference was driven mainly by improvement in diagnostic scores, with the mean difference being 11.6% (p = 0.01, 95% CI = 2.4 to 20.8). Regression analysis showed that the more difficult the case, the greater the benefit of QMR. CONCLUSIONS: Quick Medical Reference may be a useful adjunct to interns in formulating diagnostic strategies for difficult clinical cases. However, since optimal conditions were chosen for QMR benefit in this study design, the small benefit in test scores must be weighed against the time required to teach QMR to interns.

Adult↗
PubMed1994

Induced delivery of anencephalic fetuses: a response to James L. Walsh and Moira M. McQueen.

James Walsh and Moira McQueen accurately conclude that the early delivery of anencephalic fetuses is morally acceptable, but the reasoning they use to reach that conclusion is flawed. First, the principle of double effect does not require a weighing of good and evil, but rather seeks a sufficient reason for tolerating the physical evil indirectly intended. Second, the principle of double effect requires a clear distinction between physical and moral causality. Third, the Catholic moral tradition will not admit direct and intended killing of the innocent. Rather, early delivery of anencephalic fetuses is permissible because of the pathology associated with delivery of anencephalic fetuses at full term. Thus, the early delivery of an anencephalic infant is acceptable if the purpose of the moral act is avoiding a pathological condition on the part of the mother.

Anencephaly↗
PubMed1994

Risk factor analysis of peri-neonatal mortality in rural Guatemala.

Peri-neonatal mortality is a serious health problem in Guatemala, especially in rural areas where most deliveries occur at home and are overseen by traditional birth attendants (TBAs) who function in the role of midwives. The three aims of the work reported here were to identify important predictors of peri-neonatal mortality within a rural area of Guatemala; to assess the effects of traditional and modern health care providers on such mortality; and to find ways of identifying high-risk women who might benefit from transfer to a hospital or clinic. For these purposes a case-control study was conducted of 120 women in the rural department of Quetzaltenango who had lost their babies from the 20th week of pregnancy through the 28th day of life. These women and 120 controls were interviewed in their homes by trained physicians, using questionnaires in Spanish or the appropriate Indian dialect, and the results were analyzed through a series of statistical tests. It was found that the complications of pregnancy and delivery with the greatest statistical significance were prematurity, malpresentation, and prolonged labor. Population-based attributable risks of these complications demonstrated that they accounted for significant proportions of the observed peri-neonatal mortality. While these conditions cannot be eliminated, within the rural Guatemalan context it appears that early referral of women with these complications to more specialized care settings could result in improved delivery outcomes.

Adolescent↗
PubMed1994

Meta-analysis of highly selective vagotomy versus truncal vagotomy and pyloroplasty in the surgical treatment of uncomplicated duodenal ulcer.

OBJECTIVE: To compare critically by meta-analysis the postoperative outcomes after truncal vagotomy and pyloroplasty (TVP) and after highly selective vagotomy (HSV). DATA SOURCES: A search was conducted on MEDLINE with the keywords "peptic ulcer" and "vagotomy". Bibliographics of the articles retrieved and review articles pertaining to the subject were scanned further. STUDY SELECTION: Included were only published prospective, randomized controlled trials comparing TVP and HSV in the English-language literature up to April 1991. Twelve studies were found. DATA EXTRACTION: Two authors, working independently, abstracted raw data on mortality, recurrence, dumping, diarrhea and postoperative Visick grading. DATA SYNTHESIS: A ratio greater than 1.0 indicates a higher proportion occurring with TVP and less than 1.0 a higher proportion with HSV. [Table: See Text] CONCLUSION: The results suggest that the likelihood of adverse long-term sequelae is higher with TVP whereas the likelihood of recurrence is higher with HSV.

Confidence Intervals↗
PubMed1993

Effect of alpha-interferon treatment in patients with hepatitis B e antigen-positive chronic hepatitis B. A meta-analysis.

PURPOSE: To determine whether alpha-interferon is effective in terminating viral replication and in eradicating the carrier state in patients with chronic hepatitis B virus (HBV) infection. DATA SOURCES: Randomized controlled studies published in the English literature between January 1966 and June 1992 were identified through a MEDLINE computer search. STUDY SELECTION: Fifteen randomized controlled studies with a total of 837 adult chronic HBV carriers who were positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were identified. Studies were included if patients were treated for at least 3 months and followed for at least 6 months after cessation of therapy. RESULTS: Overall, the loss of HBsAg occurred 6% more often in interferon-treated patients than the natural seroconversion seen in controls (7.8% compared with 1.8%, P = 0.001), and the loss of viral replication occurred approximately 20% more often in treated patients than in controls (33% compared with 12% for loss of HBeAg and 37% compared with 17% for the loss of HBV DNA, P = 0.0001) if patients received interferon for 3 to 6 months and were followed for 6 to 12 months. Interferon also had a significant treatment effect on the development of antibodies to HBsAg (anti-HBs), antibodies to HBeAg (anti-HBe), and on the normalization of alanine aminotransferase levels. CONCLUSIONS: Alpha-interferon is effective in terminating viral replication and in eradicating the carrier state in patients with chronic HBV infection who are HBeAg positive when these patients are treated for 3 to 6 months and followed for 6 to 12 months after cessation of therapy. Follow-up studies are required to determine whether interferon reduces the risk for developing cirrhosis or hepatocellular carcinoma.

Adolescent↗
PubMed1993

High level thrombospondin 1 expression in two NIH 3T3 cloned lines confers serum- and anchorage-independent growth.

Thrombospondin (TSP) is a trimeric molecule synthesized by a variety of normal and transformed cells and secreted into the extracellular matrix. A number of studies have shown TSP to be intimately involved in the regulation of cellular proliferation. These include the findings that TSP is a mitogen-inducible immediate-early response gene; it localizes to areas of cellular proliferation in the developing mouse embryo; it augments the proliferative response to epidermal growth factor; anti-TSP monoclonal antibodies block cell proliferation; and TSP levels correlate directly with the growth and invasive phenotype and inversely with the degree of differentiation of squamous carcinoma cells. To determine whether TSP could behave as an oncogene, conferring serum and anchorage independence, NIH 3T3 cells were stably transfected with a TSP expression vector. Clones producing high levels of TSP displayed enhanced viability and a proliferative advantage in serum-reduced media. Moreover, this growth advantage could be specifically negated by treatment of the transfected cells with anti-TSP monoclonal antibodies. While the TSP overexpressing clones were capable of anchorage-independent growth in soft agar, surprisingly, they were incapable of forming tumors in nude mice, possibly due to the in vivo antiangiogenic activity of TSP. Regardless, these studies demonstrate that overexpression of thrombospondin, a constituent of the extracellular matrix, results in serum and anchorage independent growth, attributes normally associated with the transformed phenotype.

3T3 Cells↗
PubMed1993

A randomized trial of a decisional aid for mental capacity assessments.

The objective of this study was to evaluate the clinical utility of a decisional aid for mental capacity assessments which was developed using a group judgment methodology. This was carried out by a randomized, controlled trial. The subjects comprised 64 University of Toronto psychiatry residents in postgraduate years 1 through 4. Residents were randomized to carry out mental capacity assessments on simulated cases with, or without, the use of the decisional aid. The main outcome measure was the extent of agreement between the mental capacity determinations of residents and those of experts. There was no difference between the intervention and control groups with respect to the overall mean level of agreement with experts (0.87 vs 0.86, p = 0.88; 95% confidence interval for the difference between the study groups, -0.07 to +0.08). A logistic regression analysis, which adjusted for imbalances between the groups, also revealed no difference between the groups in their agreement with experts. The mean time per competency assessment was significantly longer in the intervention group (19.1 vs 10.8 min; p < 0.001). It was concluded that the decisional aid did not improve the ability of the psychiatry residents to make mental capacity assessments on simulated cases. Despite relatively limited formal training, the psychiatry residents had a high level of agreement with experts.

Adult↗
PubMed1992

Characterization of mouse thrombospondin 2 sequence and expression during cell growth and development.

Thrombospondin (TSP) is an extracellular matrix glycoprotein whose expression has been associated with a variety of cellular processes including growth and embryogenesis. The recent discovery of the existence of a second mouse TSP gene necessitates careful examination of the discrete biochemical and functional properties associated with each molecule. In this report, the primary structures of human TSP, mouse TSP1 (mTSP1), mouse TSP2 (mTSP2), and chicken TSP are compared; and the expression of mTSP1 and mTSP2 during embryogenesis and growth factor-mediated cell proliferation is examined. The cloning and sequencing of the entire coding regions of mTSP1 and mTSP2 revealed considerable conservation of residues critical for TSP structure and function; these data suggest that TSP2 is capable of trimer formation and many of the same cell-surface and ligand interactions that mediate TSP function. Comparison of the various TSP sequences also allowed the assignment based on sequence homology of previously reported human TSP as TSP1 and chicken TSP as TSP2. mTSP2, like mTSP1, was shown to be a primary response gene when quiescent Swiss 3T3 cells were stimulated with serum, platelet-derived growth factor BB, basic fibroblast growth factor, or interleukin-1 beta. Interestingly, TSP1 and TSP2 exhibited markedly different tissue- and stage-specific patterns of mRNA expression during mouse embryogenesis, implying that the two TSP molecules possess discrete functional properties important for development. Additionally, the TSP genes (Thbs1 and Thbs2) were mapped to single loci on mouse chromosomes 2 and 17, respectively.

3T3 Cells↗
PubMed1992

Pain relief: the perspective of Catholic tradition.

Efforts to study patient care from the perspective of Catholic ethics date back four centuries. In the course of this history, a prominent issue has always been management of pain and the efforts to avoid pain. Thus, Catholic theologians were concerned about the effects of pain medication upon the psychic function and considered whether or not hastening death for suffering people was allowed and the ethical norms for using opioids to remove pain when death is imminent. Moreover, the issue of "overmedication" for difficult or elderly patients has been a concern. The President's Commission on Ethics in Medicine and Human Research has utilized many of the principles developed by Catholic theologians when considering the matter of pain relief for dying persons.

Attitude to Death↗
PubMed1992

Incorporating variations in the quality of individual randomized trials into meta-analysis.

Meta-analysis is a method of synthesizing evidence from multiple sources. It has been increasingly applied to combine results from randomized trials of therapeutic strategies. Unfortunately there is often variation in the quality of the trials that are included in meta-analyses, limiting the value of combining the results in an overview. This variation in quality can lead to both bias and reduction in precision of the estimate of the therapy's effectiveness. There are a number of methods for quantifying the quality of trials including the detailed Chalmers system and simple scales. The nature of the relationship between these quality scores and the true estimate of effectiveness is unknown at this time. We discuss four methods of incorporating quality into meta-analysis: threshold score as inclusion/exclusion criterion, use of quality score as a weight in statistical pooling, visual plot of effect size against quality score and sequential combination of trial results based on quality score. The last method permits an examination of the relation between quality and both bias and precision on the pooled estimates. We conclude that while it is possible to incorporate the effect of variation of quality of individual trials into overviews, this issue requires more study.

Bias↗
PubMed1992

Application of a stopping rule based on total treatment failures: the postoperative Crohn's disease trial.

The Postoperative Crohn's Disease Trial (PCDT), a placebo-controlled randomized trial of Rowasa I in the prevention of postoperative recurrence of Crohn's disease, is used as an example of how a stopping rule based on total endpoint occurrences can provide considerable advantage over standard fixed sample size methods. It can be used when the primary outcome is occurrence or time to occurrence and does not raise the troublesome issues regarding the unblinding of group differences that other sequential methods create. The main advantage of the total endpoint stopping rule is that it provides set power. Standard fixed sample size designs provide a given power only on average. The power actually achieved in a particular fixed sample size trial is largely determined by the overall observed rate of endpoint occurrences. This claim about the total endpoint stopping rule is well established in the statistical literature and, as well as outlining the mathematical details in an Appendix, we use computer simulation of the PCDT to demonstrate that use of the stopping rule will allow termination of the trial while maintaining power and type I error at a predetermined level.

Aminosalicylic Acids↗
PubMed1992

Regulatory intensity, hospital size and the formalization of medical staff organization in hospitals.

Using a theory of organizational response to regulation, this study examined the effects of regulatory intensity and hospital size on the formalization of medical staff organization in Canadian hospitals. The general hypothesis was that, in provinces with greater regulatory intensity, hospitals would exhibit greater formalization of medical staff, and greater involvement of physicians in hospital governance and management; larger hospitals would have greater formalization of medical staff than smaller hospitals. Data from 574 hospitals indicated that both hospital size and provincial regulatory intensity were important factors predictive of the overall formalization of medical staff organization. Depending upon the provincial location, hospitals have developed different patterns of formalizing their medical staff structures.

Canada↗
PubMed1992

Knowing and practicing ethics.

The interrelationship between ethics and child and adolescent psychiatry is discussed, particularly as it relates to clinical practice. Three principles for ethical clinical practice are presented from a philosophical perspective and illustrated with two case vignettes. A formulation is reached that states that ethical theory parallels clinical theory.

Adolescent↗
PubMed1991

A second, expressed thrombospondin gene (Thbs2) exists in the mouse genome.

The diverse and occasionally conflicting properties described for the extracellular, cell surface-associated protein thrombospondin (TSP) have raised the possibility that functionally distinct forms of the protein exist in the same organism. We have isolated and characterized a partial cDNA clone for mouse TSP that is clearly homologous to, but distinct from, the coding sequence for mouse TSP deduced from a mouse genomic clone (Bornstein, P., Alfi, D., Devarayalu, L., Framson, P., and Li, P. (1990) J. Biol. Chem. 265, 16691-16698). This second TSP, which we term thrombospondin 2, is the product of a separate gene (Thbs2) and is expressed in a variety of mouse tissues in a pattern that differs from that for TSP1. Based on their translated amino acid sequences, it seems likely that TSP1 and TSP2 will be found to have both common and unique properties and that the functional consequences of TSP production will reflect the ratio of the levels of these two related proteins.

Amino Acid Sequence↗