Improving the safety of neuromuscular blocking agents: a statement from the USP Safe Medication Use Expert Committee.

PURPOSE: Recommendations of the interdisciplinary Safe Medication Use Expert Committee of the United States Pharmacopeia (USP) to assist health care professionals, manufacturers, and organizations in handling neuromuscular blocking agents (NMBAs) safely and effectively are discussed. SUMMARY: Review and analysis of the USP Medication Errors Reporting Program and MEDMARX program databases showed a continuing risk of patient harm or death due to errors with NMBAs. Medication errors involving wrong concentrations, wrong doses, wrong drugs, look-alike packaging, and sound-alike names, combined with lack of monitoring and communication, have been associated with the use of NMBAs in health care institutions. Serious adverse events occur when NMBAs are used without adequate safeguards. Recommendations for improving safety were developed through review and discussion of root causes and areas of concern with these medications. CONCLUSION: Medical errors with NMBAs continue to result in patient morbidity and mortality. Increased awareness and action on the part of all parties involved are needed to improve the safety of this class of medications.     

From Braxton Hicks to preterm labour: the constitution of risk in pregnancy.

With the recent introduction of preterm birth prevention programs there has been a shift in our understanding of what the presence of contractions during pregnancy means and a reconstituting of risk in ways that position increasing numbers of women at risk for preterm birth. This paper highlights the findings of a study exploring the influences of risk discourses on women's experiences of preterm labour. The primary goals of this institutional ethnographic study were to describe the effects of societal discourses, institutional structures, and nursing work processes on the everyday lives of childbearing women experiencing preterm labour. The findings suggest that risk discourses exert social control over pregnant women and result in fear, guilt, feelings of being judged or punished, and an overwhelming sense of personal responsibility for preventing preterm birth.The study also exposes ways in which biomedical constructions of risk and preterm labour affect the organization of health services, including nursing practice.     

Reproducibility of ultrasound pachymetry using the Sonogage Corneo-Gage Plus 2.

PURPOSE: The aim of this study was to determine the reproducibility of measurements made using the Sonogage Corneo-Gage Plus 2 (Cleveland, Ohio) ultrasound pachymeter of total corneal and corneal epithelial thickness in 5 different regions of the cornea. METHODS: Twenty-seven subjects at the New England College of Optometry (NECO) and 20 subjects at the Southern College of Optometry (SCO) were enrolled in this study. Measurements were taken of the central cornea as well as the nasal and temporal regions of the midperipheral and peripheral regions of the right cornea of each subject. Identical measurements were again taken in these subjects 1 week later at approximately the same time of day. Within-subject variations were then assessed using paired t tests. RESULTS: The only significant measurement differences that were found between visits were for full corneal thickness at both the nasal and temporal midperipheral locations. The mean differences for these locations were 13.5 microm and 13.7 microm, respectively. CONCLUSIONS: Epithelial corneal thickness and central and peripheral total corneal thickness measurements using the Corneo-Gage Plus 2 pachymeter were reproducible; however, midperipheral total corneal thickness measurements showed poor reproducibility.     

BJ-48, a novel thrombin-like enzyme from the Bothrops jararacussu venom with high selectivity for Arg over Lys in P1: Role of N-glycosylation in thermostability and active site accessibility.

BJ-48, a serine protease from the venom of Bothrops jararacussu, was purified to homogeneity using affinity chromatography on p-aminobenzamidine-agarose followed by HPLC gel filtration. BJ-48 presented 52kDa by SDS-PAGE analysis and 48,036Da by electron spray mass spectrometry. The enzyme was shown to be highly glycosylated with 42% of N-linked carbohydrates composed of Fuc(1):GalN(4):GlcN(5):Gal(1):Man(2) and a high content of sialic acid residues (8-12%). BJ-48 had optimal esterase activity at pH 7.5 and displayed maximum catalytic rate at 50 degrees C. Its hydrolytic activity was strongly inhibited by aprotinin and dithiothreitol while N-tosyl-l-phenylalanine chloromethyl ketone, 6-aminocaproic acid, E-64 and soybean trypsin inhibitor (SBTI) were ineffective. The kinetics of BJ-48 with chromogenic substrates revealed an unprecedented selectivity (10(4)-fold) for Arg over Lys in P1. BJ-48 proved to be a thrombin-like enzyme (TLE) with a specific fibrinogen-clotting activity of 73.4NIH units/mg. The TLE rapidly digested human fibrinogen Bbeta chain, but the Aalpha chain was cleaved specifically to release fibrinopeptide A with k(cat)/K(m)=2.1muM(-1)s(-1). The TLE showed no activity toward other thrombin substrates like protein C, protease-activated receptor-1 or inhibitors such as hirudin and antithrombin. A non-denaturing procedure using PNGase F and neuraminidase followed by hydrophobic interaction chromatography was employed to obtain active BJ-48 forms with variable carbohydrate content. Compared to the native enzyme, total or partially deglycosylated BJ-48 forms presented up to 2-fold reduction in their specific activities upon heating at 55/65 degrees C or treatment with SBTI. These results point out a role for BJ-48 glycosylation in thermostability and controlling the access of some canonical protein inhibitors to the active site.     

Case Study of Institution-Building by Nurse Bertha Wright and Colleagues

Purpose: To illuminate the history of nurses' participation in institution-building in the early 1900s, using the Baby Hospital in Oakland, California (now called Children's Hospital Oakland) as a case.
Design: Historical research using a framework of women's history theory focused on the women who founded Oakland's Baby Hospital, 1910–1930.
Method: Data collection included studying original sources, archival material, and interviews. Data evaluation included external criticism for authenticity and genuineness, and internal criticism for accuracy and bias.
Findings: In 1912, nurse Bertha Wright and social worker Mabel Weed, with a circle of community women, including Jessica Peixotto and Jean Howard McDuffie, established the Baby Hospital. Their activism included home visits, education, research, publications, political lobbying, and state policy and program development. At the center of this activity, was the lifelong commitment of Wright and Weed, who created new definitions of family. With social changes in the late 1920s, the male Board of Directors seized control of the hospital, and relegated women to auxiliary roles.
Conclusions: Health and social issues of the United States at the turn of the century are still problematic as a new century approaches and pertain to maternal-child health, foster care, and immigration. Feminists, including nurses, have played a central role in creating solutions. Knowledge of some of their incredible effort has been lost, particularly nursing's history in the western United States.     

Doctoral Education in Nursing for Practitioner Knowledge and for Academic Knowledge: The University of Adelaide, Australia

Australian nursing has undergone rapid academization in the past 10 years and this radical change has tended to meld the somewhat different academic traditions of North America and Britain. The introduction of doctoral education in nursing in 1987 has led to a massive increase in scholarly activity and to the preparation of talented leaders. We concur with the view expressed by Henry (1997), "I am convinced that the problems we face in the nursing services would be much more creatively solved if the majority of our doctoral programs prepared young, energetic nurses, early in their career, for clinical practice, not for research and teaching" (p. 162).     

Platelet cold agglutinins: a flow cytometric analysis.

Spontaneous EDTA-independent cold platelet agglutination is a rare phenomenon that produces pseudothrombocytopenia when blood samples are analyzed in automated cell counters. We report a case of platelet cold agglutinins and an analysis by flow cytometry. A 49 year old woman presented with abnormal vaginal bleed secondary to uterine fibroids. Platelet clumping was observed in blood samples taken in EDTA-, heparin- and citrate-containing tubes. In flow cytometric tests, patient serum agglutinated 16% of normal platelets at 22 degrees C, and 7% of platelets after incubation at 37 degrees C; in contrast, 3% and < 1% of platelets were agglutinated at 22 and 37 degrees C, respectively, after incubation with normal serum. Minimal agglutination (< 10%) was observed with patient serum at a titre of 1:5 or at temperatures > 30 degrees C. After incubation at 4 degrees C, IgM antibody and C3 were increased on the patient's platelets; no significant amount of IgM or C3 was detected on normal platelets. The specificity of the platelet cold agglutinin was determined by competitive inhibition by monoclonal anti-CD41(GPIIbIIIa). Before the addition of monoclonal antibody, patient's serum agglutinated 16% of normal platelets at 22 degrees C; after addition of anti-CD41 only 2% of the platelets were agglutinated. This blocking effect was not observed with anti-CD42. The patient's platelets functioned normally as determined by CD62 and CD63 expression in response to thrombin, normal platelet aggregation in response to collagen, ADP, and ristocetin, and a normal template bleeding time. In summary, platelet agglutination by a platelet cold agglutinin was quantitated by flow cytometry, the responsible antibody was characterized as a low titre IgM with minimal activity > 30 degrees C, and competitive binding studies supported the GPIIbIIIa complex as the binding site for the antibody. Since the antibody did not affect platelet function, we believe that these patients will not suffer complications from their platelet cold agglutinin, but it could pose a problem under circumstances such as cardiac surgery with hypothermia.     

Fine T-Cell Subsets in Alcoholics as Determined by the Expression of l-Selectin, Leukocyte Common Antigen, and β-Integrin

Alcoholics admitted to the hospital solely for detoxication have been studied by flow cytometry to evaluate changes in the surface markers of peripheral blood leukocytes. As we have shown previously, such patients have an elevated percentage of CD8^hl lymphocytes that are HLA DR⁺; we now demonstrate that they also have striking alterations in the quantitative relationships of the fine T-cell subsets. Both CD4⁺ and CD8^hl lymphocytes have a sharply reduced percentage of the l -selectin⁺ CD45RA⁺ subset, increased percentages of the CD45RA-subsets, and several other fine subset alterations. The fine subset profile suggests, according to current correlations of phenotype and function, that both CD4⁺ suppressor inducer and CD4-dependent CD8⁺ suppressor effector cells are reduced, whereas other subsets, including CD8⁺ CTL or their precursors, are increased in relative percentages. Some of the phenotypic changes are reversible over the several days following withdrawal. In other results, the percentage of CD8^hl lymphocytes expressing CD11b (β-integrin) is shown to be reciprocal with the percentage expressing l -selectin both in normals and alcoholics. However, the regression function of CD11b vs. l -selectin on CD8^hl cells is different for the alcoholics than for the normals, indicating an abnormality in the regulation of the expression of these two adhesion markers. Taken together, this abnormality of adhesion molecules and the fine subset alterations previously described indicate widespread changes in the peripheral lymphocytes of currently drinking alcoholics. These changes suggest functional deficiencies that may include alterations of lymphocyte traffic and other adhesion-dependent functions, and a shift in the balance of regulatory interactions.     

Cytokines as an adjuvant to tumor vaccines: Efficacy of local methods of delivery

Background: We examined alternative methods of delivering cytokines as an adjunct for priming lymph node (LN) cells draining sites of vaccine inoculation for the purpose of generating immune cells for adoptive immunotherapy. Methods: Using syngeneic murine tumors we examined the ability of IL-2, IL-4, or GM-CSF delivered locally to a site of tumor inoculum to induce antitumor reactive draining LN cells. Mice were inoculated subcutaneously with tumor cells transduced to secrete cytokine; tumor cells admixed with fibroblasts transduced to secrete cytokine; or intralesional inoculation of cytokine in established tumor to induce sensitized LN cells capable of mediating tumor regression in adoptive transfer. Results: Both IL-4 and GM-CSF cytokines were effective in enhancing the antitumor reactivity of vaccine-primed LN cells compared to IL-2, which was ineffective. The local delivery of GM-CSF by autocrine or paracrine secretion of genetically engineered cells, as well as direct intratumoral delivery was capable of upregulating LN sensitization compared to systemic administration, which did not. Conclusions: The local delivery of GM-CSF as an adjuvant for tumor vaccination can be accomplished by various methods, including direct injection, which avoids the need for gene transfer.     

Examination of pre- and posttreatment MHPG during cognitive therapy.

Sixteen unipolar depressed patients were treated with cognitive therapy for 12 weeks. Pretreatment 24-hour urinary MHPG levels were unable to predict treatment response. There was a nonsignificant trend for cognitive therapy responders to show a decrease in MHPG during treatment when compared to nonresponders.