Developing and gaining acceptance for patient care protocols

The difficulties students experience in applying theory to practice are well documented and educationalists have employed a variety of techniques in an effort to enhance effective application. This paper describes the utilization of one such teaching/learning strategy in a diploma level course in management for registered nurses and midwives. As problem-solving individual contracts of learning, 'ripple effect' plans enabled course participants to apply general principles of management theory to specific nursing management practice in their everyday world of nursing and midwifery work, making changes in practice and procedure which were visible and real.     

Energy-dependent accumulation of fluoroquinolones in quinolone-resistant Klebsiella pneumoniae strains

The intracellular accumulation of norfloxacin and pefloxacin in Klebsiella pneumoniae was evaluated. The roles of lipopolysaccharide, capsule, and outer membrane proteins were not important for the intrabacterial accumulation of fluoroquinolones in isogenic strains with known outer membrane alterations. In fluoroquinolone-resistant clinical isolates also expressing GyrA alterations, an active efflux leading to decreased accumulation of the drugs enhanced their resistance to these agents.     

Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. The Adverse Childhood Experiences (ACE) Study

BACKGROUND: The relationship of health risk behavior and disease in adulthood to the breadth of exposure to childhood emotional, physical, or sexual abuse, and household dysfunction during childhood has not previously been described. METHODS: A questionnaire about adverse childhood experiences was mailed to 13,494 adults who had completed a standardized medical evaluation at a large HMO; 9,508 (70.5%) responded. Seven categories of adverse childhood experiences were studied: psychological, physical, or sexual abuse; violence against mother; or living with household members who were substance abusers, mentally ill or suicidal, or ever imprisoned. The number of categories of these adverse childhood experiences was then compared to measures of adult risk behavior, health status, and disease. Logistic regression was used to adjust for effects of demographic factors on the association between the cumulative number of categories of childhood exposures (range: 0-7) and risk factors for the leading causes of death in adult life. RESULTS: More than half of respondents reported at least one, and one-fourth reported > or = 2 categories of childhood exposures. We found a graded relationship between the number of categories of childhood exposure and each of the adult health risk behaviors and diseases that were studied (P < .001). Persons who had experienced four or more categories of childhood exposure, compared to those who had experienced none, had 4- to 12-fold increased health risks for alcoholism, drug abuse, depression, and suicide attempt; a 2- to 4-fold increase in smoking, poor self-rated health, > or = 50 sexual intercourse partners, and sexually transmitted disease; and 1.4- to 1.6-fold increase in physical inactivity and severe obesity. The number of categories of adverse childhood exposures showed a graded relationship to the presence of adult diseases including ischemic heart disease, cancer, chronic lung disease, skeletal fractures, and liver disease. The seven categories of adverse childhood experiences were strongly interrelated and persons with multiple categories of childhood exposure were likely to have multiple health risk factors later in life. CONCLUSIONS: We found a strong graded relationship between the breadth of exposure to abuse or household dysfunction during childhood and multiple risk factors for several of the leading causes of death in adults.     

Effects of practice and learner control on short- and long-term gain and efficiency

This study investigated the effects of practice opportunities and learner control on short- and long-term learning from a computer-based introductory statistics curriculum. In all, 380 participants were assigned to one of five conditions. The first four conditions differed in terms of the number of problems to solve per problem set. The fifth condition allowed learners to choose the amount of practice. A subset (n = 120) of the original participants returned for testing following a six-month interval. Overall, the fixed-practice conditions showed learning gains that varied in relation to the amount of practice (i.e., more was better). The data from the learner-control condition was unexpected, showing learning gains comparable with the most extended practice condition yet the fastest tutor-completion times. We discuss implications of these findings in relation to the design of efficacious instruction. Actual or potential applications of this research include the modification of computer-based instruction that can enhance individuals' learning efficiency and outcome scores.     

Phagocytosis of Escherichia coli by insect hemocytes requires both activation of the Ras/mitogen-activated protein kinase signal transduction pathway for attachment and beta3 integrin for internalization

Insect hemocytes in response to lipopolysaccharide (LPS) of Gram-negative bacteria facilitate binding and internalization of either cell-associated or cell-free LPS (Charalambidis, N. D., Foukas L. C., and Marmaras V. J. (1996) Eur. J. Biochem. 236, 200-206). An early event in LPS signaling in hemocytes involves protein tyrosine phosphorylation (Charalambidis N. D., Zervas C. G., Lambropoulou M., Katsoris P. G., and Marmaras V. J.(1995) Eur. J. Cell Biol. 67, 32-41). Here we report further data of LPS-mediated signal transduction responsible for Escherichia coli phagocytosis. We demonstrate that both adhesion of hemocytes to substrata and LPS stimulation can cause activation of p44(MAPK) in Ceratitis capitata hemocytes but with distinct kinetics indicating different functions. In addition, we showed that Drk, a homolog protein to the mammalian GRB2, is implicated in the transmission of LPS signaling, indicating that the Ras/mitogen-activated protein kinase pathway is involved. Either the cell-free or the cell-associated LPS appears to attach to the hemocyte surface by the same mechanism that is based on the cross-linking of LPS to membrane-associated p47 via the intermediacy of tyrosine derivatives generated by the action of phenol oxidase. By contrast, the cell-free LPS internalization into the hemocytes differs from the cell-associated LPS internalization. For E. coli internalization integrin receptors as well as cytoskeletal rearrangements are required, as judged by inhibition of E. coli internalization in the presence of the RGD peptide, beta3-integrin antibodies, and cytochalasin D.     

Truncation of peptide deformylase reduces the growth rate and stabilizes solvent production in Clostridium beijerinckii NCIMB 8052

The wild-type strain of Clostridium beijerinckii NCIMB 8052 tends to degenerate (i.e., lose the ability to form solvents) after prolonged periods of laboratory culture. Several Tn1545 mutants of this organism showing enhanced long-term stability of solvent production were isolated. Four of them harbor identical insertions within the fms (def) gene, which encodes peptide deformylase (PDF). The C. beijerinckii fms gene product contains four diagnostic residues involved in the Zn2+ coordination and catalysis found in all PDFs, but it is unusually small, because it lacks the dispensable disordered C-terminal domain. Unlike previously characterized PDFs from Escherichia coli and Thermus thermophilus, the C. beijerinckii PDF can apparently tolerate N-terminal truncation. The Tn1545 insertion in the mutants is at a site corresponding to residue 15 of the predicted gene product. This probably removes 23 N-terminal residues from PDF, leaving a 116-residue protein. The mutant PDF retains at least partial function, and it complements an fms(Ts) strain of E. coli. Northern hybridizations indicate that the mutant gene is actively transcribed in C. beijerinckii. This can only occur from a previously unsuspected, outwardly directed promoter located close to the right end of Tn1545. The Tn1545 insertion in fms causes a reduction in the growth rate of C. beijerinckii, and, associated with this, the bacteria display an enhanced stability of solvent production. The latter phenotype can be mimicked in the wild type by reducing the growth rate. Therefore, the observed amelioration of degeneration in the mutants is probably due to their reduced growth rates.     

Halohydrin analogues of cryptophycin 1: synthesis and biological activity

The chloro-, bromo-, and iodo-derivatives 2-4 of the antimitotic drug cryptophycin 1 were synthesized by opening the epoxide ring. The biological activities of the compounds were tested in an in vitro microtubule assembly and a cell proliferation assay. The chloro-derivative 2 showed lower activity in the tubulin assay compared to 3 and 4, but they all showed similar inhibition in the proliferation assay.     

Increased shelf-life of fosphenytoin: solubilization of a degradant, phenytoin, through complexation with (SBE)7m-beta-CD

BACKGROUND: Rates of in-hospital death after coronary artery bypass grafting (CABG) have been studied in many regions of Canada as possible indicators of hospital-specific quality of care. This nationwide study examined observed and risk-adjusted death rates for 23 Canadian hospitals performing CABG. METHODS: Hospital discharge data were obtained from the Canadian Institute for Health Information and were used to identify all CABG procedures performed in Canadian hospitals in fiscal years 1992/93 through 1995/96. Cases from Quebec hospitals were not studied because hospitals in that province do not report to the institute. Observed death rates were evaluated, and a logistic regression model was used to calculate a risk-adjusted death rate for each hospital for the 4-year period studied. Changes over time in hospital-specific death rates were also examined. RESULTS: A total of 50,357 CABG cases were studied, with an overall death rate of 3.6%. Interhospital comparisons showed that average severity of illness varied considerably across hospitals. Despite risk adjustment accounting for this variable severity, there was considerable variation in adjusted death rates across the 23 hospitals, from 1.95% to 5.76% (p < 0.001 for difference across hospitals). For some hospitals, death rates decreased between 1992/93 and 1995/96, whereas for others the rates were stable or increased. INTERPRETATION: Risk-adjusted rates of in-hospital death after CABG vary widely across Canadian hospitals. There may be differences in quality of care across hospitals, and focused quality-improvement initiatives may be necessary in some institutions.     

The entry of [D-penicillamine2,5]enkephalin into the central nervous system: saturation kinetics and specificity

The delta opioid receptor-selective, enzymatically stable peptide [D-Penicillamine2,5]enkephalin (DPDPE) has recently acquired special significance with the identification of a saturable uptake system for this analgesic into the CNS. The aim of the present study was to characterize further the entry of [3H]DPDPE into the brain and CSF by means of a bilateral in situ brain perfusion method. Initial experiments revealed a saturable [3H]DPDPE uptake into the brain that followed Michaelis-Menten type kinetics with a K(m) value of 45.5 +/- 27.6 microM, a V(max) value of 51.1 +/- 13.2 pmol x min(-1) x g(-1) and a K(d) value of 0.6 +/- 0.3 microl x min(-1) x g(-1). Uptake of [3H]DPDPE into the CSF could not be inhibited (K(d) = 0.9 +/- 0.1 microl x min(-1) x g(-1)). Entry of [3H]DPDPE into the CNS was not inhibited in the presence of 10 mM 2-aminobicyclo-[2,2,1]-heptane-2-carboxylic acid (BCH) or 50 microM ICI 174,864, which suggests that the saturable mechanism does not involve the large neutral amino acid transporter or binding to opioid receptors. It would also appear that [3H]DPDPE is not in competition with either poly-L-lysine or insulin to enter the CNS. However, both of these substances significantly increased the CNS entry of [3H]DPDPE but not that of the vascular space marker [14C]sucrose, and this may have valuable clinical implications. It is not known at present which saturable uptake mechanism is responsible for the CNS entry of [3H]DPDPE, but overall the results suggest a carrier-mediated transport system.