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Biomedical subjects

V MacDonald

Publications and source records attributed to V MacDonald.

14 recordsLinked to original sources

Reversible cross-linking and CO treatment as an approach in red cell stabilization.

We explored the use of the reversible cross-linking reagent dimethyl 3,3-dithiobispropionimidate (DTBP) in combination with CO treatment as an approach to stabilizing erythrocyte structure and function. Erythrocytes were cross-linked with different concentrations of DTBP for different times. DTBP increased erythrocyte osmotic stability, blocked lysolecithin-induced echinocytosis, and decreased erythrocyte deformability in a concentration- and time-dependent manner. Reversal of the cross-linking with the reducing agent dithioerythritol (DTE) restored osmotic fragility and response to lysolecithin as well as deformability. Complete reversal, however, is a function of the DTBP concentration and the time of cross-linking. The effects of cross-linking with 5 mM DTBP for 1 h were completely reversible after treatment with 10 mM DTE for 20 min. Longer incubation times or higher concentrations of DTBP resulted in partial reversal by DTE of the effects produced by DTBP. Cross-linking and reversal only slightly reduced the ATP content. The hemoglobin contained in the cross-linked and reversed cells could still undergo reversible oxygenation and deoxygenation. Erythrocytes were pretreated with CO, cross-linked with 5 mM DTBP for 1 or 3 h, loaded with a solution containing 500 mM glucose for 24 h, and freeze-dried in a medium containing 15% (w/v) albumin. Rehydration followed in distilled water. Complete recovery, measured as the percentage of free hemoglobin, was achieved for cells cross-linked with 5 mM DTBP for 3 h and freeze-dried to a final water content of 10-15%. Non-cross-linked cells lysed 100% on rehydration in distilled water. No methemoglobin (MetHb) formation as a result of freeze-drying was detected in CO-treated cells. In non-CO-treated cells 20% of the Hb was converted to MetHb.

Adenosine Triphosphate↗

Liposome encapsulation attenuates hemoglobin-induced vasoconstriction in rabbit arterial segments.

Free hemoglobin (Hb) induces a potent vasoconstrictor response that may limit its therapeutic application as a red blood cell replacement. We have investigated whether encapsulation of stroma-free Hb (SFHb) or cross-linked Hb (alpha alpha-Hb) in liposomes modulates Hb vasoactivity in isolated blood vessels. Relaxation of rabbit thoracic vessels was measured before and after exposure to acellular SFHb, alpha alpha-Hb, and liposome-encapsulated SFHb or alpha alpha-Hb. SFHb and alpha alpha-Hb caused significant inhibition of carbachol-induced relaxation at 0.5 mg/dl, whereas encapsulation inhibited vessel relaxation at 30- to 60-fold higher Hb concentrations. The contractile response of rabbit ear arterial segments to electrical stimulation in the presence of acellular alpha alpha-Hb resulted in a 150% increase (EC150) in contractile amplitude at 0.23 mg/dl, whereas the EC150 for encapsulated alpha alpha-Hb was 13.7 mg/dl. Mechanistic studies of the vasoconstrictor activity of Hb demonstrated that acellular alpha alpha-Hb had no effect on norepinephrine release in the rabbit ear artery. In addition, neither acellular nor encapsulated alpha alpha-Hb preparations inhibited endothelial nitric oxide (NO) synthase activity isolated from bovine pulmonary artery. However, inhibition of vessel relaxation by acellular or encapsulated alpha alpha-Hb was reversed by the NO donor S-nitrosylpenacillamine, implicating Hb-NO binding as a possible mechanism for the vasoconstrictor response. In vitro stopped-flow kinetic studies of Hb-NO binding showed similar rates of reaction for conversion of oxyhemoglobin to methemoglobin (metHb; < 2 ms), followed by rapid conversion of metHb to NO-Hb (300 ms) for both acellular and encapsulated alpha alpha-Hb, demonstrating that liposome encapsulation does not retard NO-Hb binding. The attenuated vasoactivity of encapsulated Hb may, therefore, result from the limited access of encapsulated Hb to NO imposed by the physical size of the liposome and reduced penetration of Hb across the vascular endothelium.

Animals↗

Implementing innovations in health care settings.

Innovations in health care settings are occurring at an unprecedented rate. New methods and ideas include computerized pumps, computer systems for documentation and communication, and alternative approaches to patient care. To be successfully adopted by nurses, innovations require well-planned administrative, educational and clinical support. A multi-agency research study has revealed factors that should be considered when planning innovations in health care settings.

Diffusion of Innovation↗

Prosocial behavior in hyperactive boys: effects of stimulant medication and comparison with normal boys.

To clarify the effects of stimulant medication on hyperactive (ADHD) children's prosocial as well as aversive behaviors toward peers, 19 hyperactive boys, aged 7-12, were observed as they acted as "leaders" for groups of 2-4 unfamiliar younger children. In a double-blind crossover design, subjects were observed twice, once on placebo and again on a moderate (0.6 mg/kg) dose of methylphenidate (Ritalin). Thirteen comparison boys, without problems in attention and behavior, were also observed in the same leader roles. Relative to comparison boys, hyperactive boys on placebo were more socially engaged, used more aversive leadership techniques, and were rated as less likable by the younger children in their groups. Aversive social behaviors were the strongest predictors of being disliked by the younger children. No differences were found between comparison and unmedicated hyperactive boys for any aspect of prosocial behavior. Stimulant medication had a general dampening effect on social behavior, significantly reducing social engagement and increasing (mild) dysphoria relative to the placebo condition. The implications of these findings for understanding and treating the peer relationship difficulties of hyperactive children are discussed.

Attention Deficit Disorder with Hyperactivity↗

Immunoglobulin bound to platelets as immune complexes or specific antibody in specimens from acquired immunodeficiency syndrome and immune thrombocytopenic purpura.

Acquired immunodeficiency syndrome (AIDS), lymphadenopathy syndrome (LAS), and immune thrombocytopenic purpura (ITP) specimens were tested by an enzyme-linked immunosorbent assay (ELISA) for immunoglobulin (Ig) bound to platelets. All specimen evaluations were performed with General Diagnostic's newly developed kit procedure. The test measured but did not distinguish immune complex (IC) binding with platelet Fc receptor sites from platelet-specific antibody (PAb) binding with platelet antigen Fab-binding sites. Alkaline phosphatase-labeled antihuman IgG as conjugate detected IgG as low as 2.0 ng/ml or platelet-adsorbed, heat-aggregated IgG, simulating IC, at 2-10 ng/ml. There was a high prevalence of platelet-bound Ig in AIDS specimens (25/25) compared with normals (2/15), detected primarily by the indirect ELISA (p less than 0.001), and a preponderance of PAb in ITP specimens (5/5) compared with normals (6/22), by the direct ELISA (p less than 0.01). AIDS specimens had a geometric mean titer (GMT) of 173 ng of IgG bound/10(7) platelets, compared with the Ig from ITP, which had a GMT of 20 (p less than .0002). Monoclonal antibody to human receptors for IgG Fc fragment (anti Fc gamma R) inhibited 69% of specimens tested as having platelet-bindable antibody. Thus, the ELISA procedure would be useful in assessing but not in differentiating platelet-bound Ig in patients with AIDS and ITP and certain other clinical groups tested.

Acquired Immunodeficiency Syndrome↗

The development of writing posture in left-handed children and its relation to sex and reading skills.

Recordings of handwriting posture were taken on left-handed children at grades 1, 3 and 5. The main findings were that most young boys eventually change from a parallel to an inverted posture, while most girls show an early preference for the non-inverted writing posture. The data are discussed in terms of current notions about why the inverted posture develops. Discussion also centers on the finding that for grade 5 boys, the parallel posture is associated with poor reading scores.

Age Factors↗

Increased blood viscosity in a patient with sickle cell anemia.

Although intracellular viscosity is greatly increased in deoxygenated sickle cells, the viscosity of blood is not, because patients' packed cell volumes (PCV) are usually extremely low (15-25%). A young women with sickle cell anemia was admitted with a typical painful crisis, and was found to have a PCV of 39% with a reticulocyte count of 3.6%. During a hospitalization of 48 h, the PCV rose to 46%; her pain subsided but her behavior became bizarre, cardiopulmonary arrest occurred, and she could not be resuscitated. At autopsy, no abnormalities were found except for congested blood vessels containing sickle cells. It was subsequently discovered that she and her family had been exposed to carbon monoxide for a week prior to admission. Blood samples from another patient studied with a PCV of 40% showed progressively decreased viscosity if they contained 13-20% carboxyhemoglobin. It is suggested that preexisting accelerated erythropoesis was further stimulated by CO, and caused "compensatory polycythemia", but that the CO prevented most of the newly formed cells from sickling and being destroyed. Admission to hospital caused a gradual disappearance of CO but the patient's PXV continued to rise. Her death may have been due to a rare form of hyperviscosity syndrome, when the level of carboxyhemoglobin in her blood fell to more normal levels and her cells regained the ability to sickle. Treatment of sickle cell anemia with an effective non-covalently bound agent could have a similar effect, if the agent were withdrawn abruptly.

Acute Disease↗

Postoperative pain management in frail older adults.

PURPOSE: To evaluate the Frail Elder Pain Management Program (FEPMP) implemented for patients who had hip fracture repairs at a community hospital in 1995. Based on standards of geriatric and pain management practice, the FEPMP included education sessions, preprinted analgesic orders, pain flow sheets, written resources, and clinical support. A Logic Model reflected the program's conceptualization. DESIGN: Preexperimental pretest and posttest design. SAMPLE: A random sample of 50 charts of patients aged 75 and older who had hip fracture repairs were audited from each of two periods: the preimplementation period (1994-95) and the postimplementation period (1997-98). METHODS: A chart audit tool was developed, tested, and used. Data were analyzed using descriptive, parametric and nonparametric statistics. FINDINGS: Surgeons' prescriptions and nurses' pain management practices improved significantly (p = .0001). Pain assessment modestly improved. Patient outcomes also improved. IMPLICATIONS FOR PRACTICE AND EDUCATION: A programmatic approach to pain management is effective for improving practice and outcomes for frail elders.

Aged↗