Ethical Reasoning Among Registered Nurses Experienced in Dementia Care

Abstract. Registered nurses regarded as “experienced and good” in dementia care were interviewed about the feeding of a severely demented patient who showed refusal-like feeding behaviour. Not one of the twenty nurses could see herself using force against her patients. Most interviewees justified their decisions to feed a severely demented patient and answered questions about whether they would change their minds if there were certain circumstances in terms of words that could be interpreted as referring to the ethical principle of beneficence. The nurses stressed the difficulty to understand the meaning of severely demented patients' feeding behaviour and decide when force-feeding occurs. When asked to rank ethical principles of importance for the decision, however, the most common answer was that they would give priority to the ethical principle of autonomy. The nurses did not see the ethical principles as separate entities, that could be applied one by one, but tried to integrate them into a whole. The findings of this study were interpreted as indicating that principled ethics is not an adequate model to describe experienced nurses' ethical reasoning.     

A sensitive isotope modification of the mixed haemadsorption test applicable to the study of prozone effects

Investigations of surface antigens of animal cells require sensitive and quantitative in vitro methods. A modification of the mixed haemadsorption technique (MHT) suitable for such purposes is presented. The indicator cells have been labelled with chromium-51. During studies of experimental conditions, including reproducibility and sensitivity, the technique was used in four model systems including histocompatibility (H-2, HL-A), species, organ and blood group antigens. Isotope labelling of the indicator cells has rendered the test more sensitive and in addition some qualitative properties of antigen—antibody interaction have been studied. The test procedure is simple and fast.     

Chlorotetracycline Induces calcium mediated shape changes in human erythrocytes

Calcium was localized in the red cell membrane by light microscopy using chlorotetracycline hydrochloride (CTC) as chelate probe. Treating human erythrocytes with CTC dissolved in saline free of divalent cations, leads to a 530 nm fluorescence emission in the cell border and to characteristic cell shape changes which were evaluated to assess intramembrane calcium distribution. CTC prevented and reverted erythrocyte crenation induced either by washing or superfusing the cells with saline. The ionophore A23187, EGTA and glucose depletion depressed the shape modifying effect of CTC. Thus, CTC appears to act on red cell shape by complex formation with membrane associated calcium. This is further confirmed by the failure of degraded CTC, devoid of metal binding capacity, to modify the crenated shape. The CTC effect can be reverted by superfusing the erythrocytes with CTC-free medium. Thus, calcium binds more tightly to the membrane than to CTC and is not displaced by the antibiotic. If the bilayer couple hypothesis [Sheetz, M.P., Singer, S.J., Proc. Natl. Acad. Sci. USA 71, 4457-4461 (1974)]applies, crenation is reverted by expansion of the inner membrane half relative to the outer membrane half. Expansion of the inner membrane half results from intercalation of CTC which binds to calcium. Thus, calcium in the red cell membrane preferentially occupies the inner leaflet of the bilayer.     

Mixed haemadsorption: A mixed antiglobulin reaction applied to antigens on a glass surface: Preparation and evaluation of indicator red cells; survey of present applications

Mixed haemadsorption should be regarded as an application of the mixed antiglobulin reaction to situations where the antigen is sessile on a glass surface. Antibody attached to the antigen when exposing the latter to an antiserum is traced by red cells carrying an antiglobulin layer which makes them adsorb to the antibody.

The indicator cells are prepared by coating them first with a layer of γ-globulin from the animal species, the antibody globulin of which they are intended to trace, and then with a layer of the corresponding antiglobulin. The most effective indicator cells were obtained by attaching antibody to natural receptors on the red cells to achieve their first coating of γ-globulin.

The preparation of indicator cells for tracing antibodies from a number of species, including human, is described.

The mixed haemadsorption technique is highly specific and has a sensitivity which is comparable to that of the most sensitive serological techniques.

Test procedures adapted for different purposes are outlined and a number of applications to experimental and clinical problems are reviewed.

     

Inhibitory effects of clonidine on the allergen-induced wheal-and-flare reactions in patients with extrinsic asthma

We investigated the possibility that clonidine, an alpha 2-adrenoceptor agonist, can reduce the wheal-and-flare reactions induced by intradermal injections of allergen in patients with extrinsic asthma. Ten adult subjects with asthma with positive skin tests to one or several pollens were selected. They received, in random order and double-blind manner, clonidine (two doses, each 75 micrograms) or placebo for 3 days, and then, after a 1-week washout period, they crossed over to the other treatment for 3 days. Treatment with clonidine reduced the area of wheal-and-flare reaction induced by allergen without significantly changing the blood pressure or the plasma cortisol level. There was a drop in the histamine content of leukocytes and in the number of eosinophils in peripheral blood after allergen challenge during the placebo treatment, whereas clonidine prevented these changes. The results suggest that treatment with clonidine can reduce the inflammatory reactions induced by allergens in subjects with extrinsic asthma.     

β1-Adrenoceptor gene variations: a role in idiopathic dilated cardiomyopathy?

A substantial body of evidence suggests involvement of the human beta1-adrenoceptor (beta1-AR) gene in the pathophysiology of dilated cardiomyopathy (DCM), a severe heart disease of significant public health impact. Beta1-AR-mediated signal transduction is dramatically altered due to downregulation, resulting in an impairment of myocardial response. The important role of genetic factors in idiopathic dilated cardiomyopathy (IDCM) recently recognized, we analyzed this prime candidate gene for genetic variation in carefully selected patients and controls. In this preliminary study, 18 single nucleotide polymorphisms were observed, 17 of which were located in the N-terminal and C-terminal region of the coding exon, resulting in 7 amino acid exchanges: Ser-49-Gly, Ala-59-Ser, Gly-389-Arg, Arg-399-Cys, His-402-Arg, Thr-404-Ala, and Pro-418-Ala. These mutations resulted in 11 different beta1-AR genotypes. Importantly, the genotypes carrying the Ser-49-Gly mutation in the N-terminus of the molecule in a heterozygous or homozygous form were observed significantly more frequently in the group of IDCM patients. The present results may provide a clue on the molecular mechanisms involved in IDCM, and add moreover interesting information on nature, distribution, and evolutionary aspects of sequence variation in human adrenergic receptor genes.     

Cationic-amphiphilic arpromidine-derived guanidines and a histamine trifluoromethyl-toluidide derivative may activate pertussis toxin-sensitive G-proteins by a receptor-independent mechanism

Formyl peptides activate superoxide anion (O₂ ^–) formation in human neutrophils and in HL-60 cells via pertussis toxin (PTX)-sensitive guanine nucleotide-binding proteins (G-proteins), and histamine (HA) mediates inhibition of O₂ ^– formation via H₂-receptors. We have studied the effects of lipophilic arpromidine-derived guanidines, which are potent, full H₂-receptor agonists in the guinea pig atrium, on O₂ ^– formation and on activation of G-proteins in HL-60 membranes and on purified G-proteins. We have also studied the effects of a HA trifluoromethyl-toluidide derivative (HTMT), a cationic-amphiphilic HA derivative which activates O₂ ^– formation in HL-60 cells through a mechanism which is independent of known HA receptor subtypes, on G-protein activation. Guanidines, at concentrations, up to 30 mol/l inhibited and, at concentrations above 30 mol/l, enhanced formyl peptide-induce O₂ ^– formation in neutrophils. In HL-60 cells, guanidines per se activated O₂ ^– formation. The stimulatory effects of guanidines on O₂ ^– formation were not inhibited by H₁- or H₂-receptor antagonists. In HL-60 membranes, guanidines and HTMT, activated high-affinity GTPase in a PTX-sensitive manner. These substances also increased GTP hydrolysis effected by transducin and G_i/G_o-proteins. Our data suggest that lipophilic guanidines and HTMT may act as receptor-independent activators of PTX-sensitive G-proteins, resulting in stimulation of O ₂ ^– formation.     

Physicochemical Characterization of Protein-Free Low Density Lipoprotein Models and Influence of Drug Loading

Purpose. Drug free and drug loaded protein-free low density lipoprotein (LDL) models consisting mainly of phospholipids, cholesterol, cholesterol esters, and triglycerides in ratios found for physiological LDL have been prepared. Their physicochemical characteristics were compared with those of physiological LDL. Methods. Different characterization methods were used: photon correlation spectroscopy, transmission electron microscopy, X-ray solution scattering, and ¹H nuclear magnetic resonance spectroscopy (NMR). Results. Particle sizes are highly dependent on the preparation method and in particular on the homogenization conditions. Electron microscopy indicates that the size distributions of model systems are much broader than those of physiological LDL. The X-ray solution scattering patterns of the model systems display a temperature dependent maximum near 3.8 nm similar to that found in the patterns of physiological LDL. NMR indicates a comparable mobility of the lipid molecules in model particles and in physiological LDL. The influence of drug loading is similar to that found earlier for physiological LDL. In particular, the incorporation of the anti-cancer drug WB 4291 seems to have a fluidizing effect on the lipids in the core region of the particles. Conclusions. The preparation method of LDL model systems is of crucial importance as only the solvent evaporation method yielded systems in the size range of physiological LDL with acceptable high lipid concentrations. The fluidizing influence of temperature and drug incorporation (WB 4291) may be a disadvantage in drug targeting.     

Blastocyst development after sperm selection at high magnification is associated with size and number of nuclear vacuoles

Spermatozoa selection at high magnification before intracytoplasmic sperm injection seems to be positively associated with pregnancy rates after day 3 embryo transfers. The aim was to demonstrate an association between the presence of vacuoles in sperm nuclei and the competence of embryos to develop to day 5. Grading of spermatozoa at x 6000-x 12,500 magnification: grade I, no vacuoles; grade II, or=1 large vacuole; grade IV, large vacuoles with other abnormalities. The outcome of embryo development in a group of 25 patients after sibling oocyte injection with the four different grades of spermatozoa showed no significant difference in embryo quality up to day 3. However, the occurrence of blastocyst formation was 56.3 and 61.4% with grade I and II spermatozoa respectively, compared with 5.1% with grade III and 0% with grade IV respectively (P < 0.001). Spermatozoa selection at high magnification using Nomarski interference contrast is useful to identify more precisely the size and the number of nuclear vacuoles that greatly exert a negative effect on embryo development to the blastocyst stage. These observations confirm previous studies pointing to possible 'early and late paternal effects', both of which may have an impact on early embryonic development.