Heartland Regional Medical Center makes a "fitting response" to medical mistakes.

Medical mistakes is an issue that challenges many healthcare providers and organizations. The challenges are professional, personal, systemswide, financial, and morally compelling; and a fully fitting response may depend on the answer to questions that H. Richard Niebuhr used to divide all ethical considerations: what is going on here; and what is the fitting response. Heartland Regional Medical Center in St. Joseph, Missouri, asked these questions about medication errors. The response model they developed, although it is very much a work in progress, shows how a facility can go from an ethical analysis to fixing the problem.

Ultraviolet and visible light spectrophotometric approach to blood typing: objective analysis by agglutination index.

BACKGROUND: A new blood typing technology based on ultraviolet (UV) and visible light spectroscopy (UV/visible spectroscopy) has been developed. Blood groups and types are determined by quantifying reproducible changes in the UV and visible light spectra of blood in the presence of agglutinating antibodies. STUDY DESIGN AND METHODS: Samples of red cells in the presence and absence of agglutinating antibodies were examined by UV/visible spectroscopy. Blood groups and types were determined by comparing the optical density spectra obtained between 665 and 1000 nm. These comparisons generate numbers (agglutination index) ranging from 0 to 100, with smaller numbers corresponding to lack of agglutination and larger numbers corresponding to agglutination. RESULTS: The optical density of agglutinated blood is dramatically different from that of unagglutinated blood. The agglutination index derived from the relative slopes of the spectra is an objective indicator of agglutination strength. An agglutination index greater than 17 consistently and accurately established blood group- and type-specific agglutination. CONCLUSION: The method accurately predicted A, B, and O blood groups, and D type in over 275 samples. Scattering theory-based calculations of relative volumes of red cells before and after agglutination show a direct correlation with the agglutination index and provide the theoretical basis of the analysis. This quantitative technique is reproducible and has the potential for automation.

Tryptophan depletion and depressive vulnerability.

BACKGROUND: Rapid and transient depletion of tryptophan (TRP) causes a brief depressive relapse in most patients successfully treated with and taking selective serotonin reuptake inhibitors, but little change in drug-free, symptomatic depressed patients. This study investigates the effects of TRP depletion in drug-free subjects in clinical remission from a prior major depressive episode (MDE). METHODS: Twelve subjects with a prior MDE, currently in clinical remission and drug-free for at least 3 months (patients), and 12 healthy subjects without personal or family history of Axis I disorder (controls), received TRP depletion. The study was conducted in a double-blind, controlled [full (102-g) and quarter-strength (25 g) 15-amino acid drinks], crossover fashion. Behavioral ratings and plasma TRP levels were obtained prior to, during, and after testing. RESULTS: All subjects experienced significant depletion of plasma TRP on both test-drinks, showing a significant dose-response relation. Healthy control subjects had minimal mood changes, but patients had a depressive response of greater magnitude. CONCLUSIONS: In the context of prior TRP depletion studies with antidepressant-treated, and drug-free symptomatic depressed patients, these results suggest that depression may be caused not by an abnormality of 5-HT function, but by dysfunction of other systems or brain regions modulated by 5-HT.

The Kansas City palliative care curriculum--medical schools improve end-of-life training.

Midwest Bioethics Center believes that encouraging palliative care training in the school milieu is one of the keys to achieving lasting improvement in end-of-life care. Therefore, a cooperative venture to increase palliative care education in medical schools was among the first strategies envisioned in the Center's PATHWAYS initiative. Its implementation, no less than its goal, requires both time and effort.

Religious themes in medical journals.

The dialogue between medicine and religion has been expected to intensify. To test the degree of interaction empirically, the contents of four clinical medical journals for the years 1981 to 1991 were examined for reference to religious themes. Religion was important in 13 of 17,345 articles. Reasons proposed for this relative neglect are hostility, lack of interest, inadequate empirical studies, and the substitution of ethics and humanities as surrogates for religion. Scholars of religion are encouraged to submit relevant material to medical journals.

Connective tissue growth factor: a cysteine-rich mitogen secreted by human vascular endothelial cells is related to the SRC-induced immediate early gene product CEF-10.

Human umbilical vein endothelial (HUVE) cells have been previously reported to express the genes for the A and B chains of PDGF and to secrete PDGF-related factors into culture media. Antihuman PDGF IgG affinity chromatography was used to purify PDGF-related activity from HUVE cell-conditioned media. Immunoblot analysis of the affinity-purified proteins with anti-PDGF IgG and antibodies specific for the A or B chain peptides of PDGF combined with chemotactic and mitogenic assays revealed that the major PDGF immunorelated molecule secreted by HUVE cells is a monomer of approximately 36-38 kD and that less than 10% of the purified biologically active molecules are PDGF A or B chain peptides. Screening of an HUVE cell cDNA library in the expression vector lambda gtl 1 with the anti-PDGF antibody resulted in the cloning and sequencing of a cDNA with an open reading frame encoding a 38-kD cysteine-rich secreted protein which we show to be the major PDGF-related mitogen secreted by human vascular endothelial cells. The protein has a 45% overall homology to the translation product of the v-src-induced CEF-10 mRNA from chick embryo fibroblasts. We have termed this new mitogen connective tissue growth factor.

Nucleoside diphosphate kinase from Xenopus oocytes; partial purification and characterization.

We have identified and partially purified a soluble nucleoside diphosphate kinase (NDP kinase) from Xenopus laevis oocytes. The enzyme preparation can catalyze the transfer of phosphate from ATP to all of the major oxy- and deoxynucleotides. It can also catalyze the transfer of a phosphorothioate group from gamma-S-ATP to an acceptor GDP forming gamma-S-GTP. Like NDP kinases from other sources, the catalytic mechanism appears to involve a phosphoenzyme intermediate which can be isolated. Transfer of phosphate from nucleoside triphosphates to protein is rapid, reaching saturation within 1 min following the addition of nucleoside triphosphates. The transfer of phosphate from phosphoprotein intermediate to nucleoside diphosphates is equally fast. While nucleoside diphosphate kinases are generally thought to require magnesium for activity, both the oocyte enzyme preparation and a commercial bovine liver enzyme preparation are only partially inhibited by short (10 min) exposures to 25 mM EDTA. Both enzyme preparations are, however, further inhibited by long incubations with this metal chelator (2 h, 70% inhibition). Zinc enhances the inhibition of NDP kinase by EDTA, but is ineffective on its own. Rapid phosphorylation in the presence of [gamma-32P]ATP and EDTA could be used to identify the phosphoenzyme intermediate in homogenates of Xenopus oocytes and facilitated its isolation. Sodium dodecyl sulfate polyacrylamide gel electrophoresis coupled with autoradiography indicated the presence of only a single phosphorylated species of Mr 21,500 in supernatants of fresh oocyte homogenates. Partial purification of this protein utilizing salt precipitation, hydrophobic-interaction chromatography and an affinity step with Affi-Gel Blue Sepharose resulted in a 100-fold purification and a 29% overall yield of NDP-kinase activity. Size-exclusion chromatography of the purified preparation yielded two peaks containing enzyme activity. They eluted with apparent molecular weights of 45,000 and 70,000, suggesting a native enzyme that is multimeric or associated with other proteins.

Biomedical information, peer review, and conflict of interest as they influence public health.

The peer review process serves a vital role in the publication of biomedical information. When properly functioning, review should focus exclusively on questions of scientific validity and should avoid becoming enmeshed in questions such as "authorization" and "data ownership." We present a case in which the dissenting views of a coinvestigator were suppressed because the principal investigator and grantee institution informed a medical journal that the coinvestigator was not "authorized" to use the data generated by a publicly funded grant and because the editor of a scholarly journal refused to review the dissenting manuscript and to submit that dissent to external reviewers for peer review. The current peer review system, as shown by this case, is unable to embrace dissent within the peer review process and to use dissent to serve scientific truth and the public interest.

KIE: The authors present a case involving the University of Pittsburgh School of Medicine in which the dissenting views of one of the authors, Cantekin, a coinvestigator for a National Institutes of Health funded trial, were surpressed from publication. The principle investigator and the grantee institution claimed that the coinvestigator was not authorized to use data from the publicly funded grant, and the editor of a scholarly journal refused to review the dissenting manuscript or submit it for external peer review. At the time this article was submitted, the case had attracted the attention of the media and of the U.S. Congress. It raises the issues of ownership of data from publicly financed research and of the failure of the current peer review process to deal with dissent in scientific publication.

Role of gamma-aminobutyric acid in antipanic drug efficacy.

All effective pharmacologic agents used to treat panic disorder augment gamma-aminobutyric acid (GABA) transmission. Anxiolytics and antidepressants that lack GABA activity are not effective in panic disorder. To test the hypothesis that GABA activity is a component of antipanic drug efficacy, the authors treated nine medication-free panic disorder subjects with oral baclofen (30 mg/day for 4 weeks) in a double-blind, placebo-controlled crossover trial. Baclofen, a selective GABA agonist, was significantly more effective than placebo in reducing the number of panic attacks and scores on the Hamilton anxiety scale, Zung scale, and Katz-R nervousness subscale. The authors discuss possible mechanisms of antipanic drug efficacy.