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Biomedical subjects

H C Wilson

Publications and source records attributed to H C Wilson.

At least 19 recordsLinked to original sources

A comparison of time-and-motion and self-reporting methods of work measurement.

OBJECTIVE: To compare results obtained from a time-and-motion study with those obtained using self-reporting. SUMMARY BACKGROUND DATA: Nurse executives are often required to provide additional patient care services with limited personnel resources. As a result, nurse executives must evaluate the appropriate allocation of nursing personnel resources. Work measurement may be used to evaluate personnel allocation. Multiple measurement approaches are available, but few studies have compared these methods. METHODS AND SUBJECTS: Eight nurses were observed by a single observer during five shifts (or approximately 40 hours per nurse). After completion of the time-and-motion study, participants were to self-report their work activities during their ensuing five shifts. Mixed-effects analysis of variance was used to determine the significance of the work measurement method on percentage of total time, number of activities, and mean time per activity by activity category. RESULTS: Two hundred ninety hours of time-and-motion study observations and 338 hours of self-report data were available for analysis. Comparable amounts of total time were reported within the various activity categories using time-and-motion and self-reporting methods. In terms of number of activities reported, a significantly higher number of activities were reported using time-and-motion. As a result, mean activity times were significantly longer using the self-reporting method compared with time-and-motion. CONCLUSIONS: Nurse executives should consider continuous self-reporting as a low-cost means of quantifying allocation of time among nursing personnel. Self-reporting, however, is not recommended for estimating the total number of activities or the mean time per activity because of perceptual differences between participants of what constitutes an activity.

Humans↗

Successful treatment of IgM paraproteinaemic neuropathy with fludarabine.

OBJECTIVES: To evaluate the response of four patients with IgM paraproteinaemic neuropathy to a novel therapy-pulsed intravenous fludarabine. BACKGROUND: The peripheral neuropathy associated with IgM paraproteinaemia usually runs a chronic, slowly progressive course which may eventually cause severe disability. Treatment with conventional immunosuppressive regimens has been unsatisfactory. Fludarabine is a novel purine analogue which has recently been shown to be effective in low grade lymphoid malignancies. METHODS: Four patients were treated with IgM paraproteinaemic neuropathy with intravenous pulses of fludarabine. Two of the four patients had antibodies to MAG and characteristic widely spaced myelin on nerve biopsy and a third had characteristic widely spaced myelin only. The fourth had an endoneurial lymphocytic infiltrate on nerve biopsy and a diagnosis of Waldenström's macroglobulinaemia. RESULTS: In all cases subjective and objective clinical improvement occurred associated with a significant fall in the IgM paraprotein concentration in three cases. Neurophysiological parameters improved in the three patients examined. The treatment was well tolerated. All patients developed mild, reversible lymphopenia and 50% mild generalised myelosuppression, but there were no febrile episodes. CONCLUSION: Fludarabine should be considered as a possible treatment for patients with IgM MGUS paraproteinaemic neuropathy.

Aged↗

Reversible tripeptide thrombin inhibitors as adjunctive agents to coronary thrombolysis: a comparison with heparin in a canine model of coronary artery thrombosis.

Direct inhibition of thrombin with agents such as hirudin and argatroban reduces reocclusion rates during experimental coronary thrombolysis. We compared the adjunctive potential of the tripeptide thrombin inhibitor D-methyl-phenylalanyl-prolyl-arginal (LY294468) during thrombolysis with tissue-type plasminogen activator (t-PA) with the less specific tripeptide thrombin inhibitor Boc-D-phenylalanyl-prolyl-arginal (LY178207) and the standard anticoagulant heparin. The left circumflex coronary artery (LCX) was isolated proximal to the first main branch, and coronary blood flow (CBF) was measured in 26 anesthetized dogs. Thrombogenesis was initiated by electrolytic injury of the intimal surface of the artery, producing an occlusive thrombus. Thrombolytic/adjunctive therapy was started 1 h later in the following groups: (a) t-PA alone (0.9 mg/kg, 1-h infusion), (b) t-PA + LY294468 (0.5 or 1 mg/kg/h, 2-h infusion), (c) t-PA + LY178207 (0.5 or 1 mg/kg/h, 2-h infusion), and (d) t-PA + heparin (80 U/kg bolus + 30 U/kg/h, 2-h infusion). LY294468 provided antireocclusive efficacy (time to reocclusion = > 200 min as compared with 65 min for t-PA alone; six of nine patent vessels vs. zero of six, respectively, at the end of the experiment), with no bleeding liability during t-PA-induced thrombolysis. Heparin and LY178207 were ineffective adjunctive agents. Heparin, however, significantly increased template bleeding times. LY294468 was effective as an adjunctive agent during thrombolysis and may represent a safer (less bleeding) and more effective adjunctive agent than heparin.

Animals↗

A critical review of menstrual synchrony research.

Two experiments and three studies reported a significant level of menstrual synchrony after subjects had been treated with applications of axillary extract from a donor subject or after subjects have spent time together. Four studies failed to replicate these results. A comparison of the studies shows the only consistent difference is that those studies not finding menstrual synchrony reported problems with subjects who had irregular cycle lengths, while those finding menstrual synchrony reported no such problems. All experiments and studies were based on the methods and research design introduced by McClintock (1971). Three errors are inherent in research based on her model: (1) an implicit assumption that differences between menses onsets of randomly paired subjects vary randomly over consecutive onsets, (2) an incorrect procedure for determining the initial onset absolute difference between subjects, and (3) exclusion of subjects or some onsets of subjects who do not have the number of onsets specified by the research design. All of these errors increase the probability of finding menstrual synchrony in a sample. One or more of these errors occurred in the experiments and studies reporting synchrony; no significant levels of menstrual synchrony occur when these errors are corrected. Menstrual synchrony is not demonstrated in any of the experiments or studies.

Adult↗

LY215840, a potent 5-hydroxytryptamine (5-HT)2 receptor antagonist, blocks vascular and platelet 5-HT2 receptors and delays occlusion in a rabbit model of thrombosis.

Certain ergolines are potent and selective 5-hydroxytryptamine (5-HT)2 receptor antagonists. Previous studies with two ergoline esters, LY53857 and sergolexole, documented their potency as 5-HT2 receptor antagonists and their metabolism in rats to a less active metabolite, 1-isopropyl dihydrolysergic acid. LY215840, an ergoline amide, has been identified as a potent 5-HT2 receptor antagonist that is not hydrolyzed to 1-isopropyl dihydrolysergic acid. In the rat jugular vein, LY215840 (3 x 109-10) to 10(-8) M) blocked 5-HT2 receptors mediating contraction to 5-HT in vitro. After i.v. and p.o. administration to rats, LY215840 was a potent 5-HT2 receptor antagonist, documented by its ability to block the pressor response to 5-HT administered i.v. Furthermore, after i.v. and p.o. administration of LY215840, blockade of vascular 5-HT2 receptors persisted in excess of 2 and 6 hr, respectively. LY215840 also blocked vascular 5-HT2 receptors in doses that did not affect alpha-1, beta-1 receptors or angiotensin II pressor responses, documenting the selectivity of LY215840 as an inhibitor of 5-HT2 and not other vascular receptors that modulate vasoconstriction. In addition to inhibiting vascular 5-HT2 receptors, LY215840 also inhibited 5-HT-amplified, ADP-induced aggregation (another 5-HT2 receptor-mediated response) in both rabbit and human platelets. Because of its ability to block both platelet and vascular 5-HT2 receptors, we studied the effectiveness of LY215840 in the rabbit carotid artery model of vascular occlusion. Low i.v. doses of LY215840 markedly prolonged time to vascular occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Pharmacological assessment of the antithrombotic activity of the peptide thrombin inhibitor, D-methyl-phenylalanyl-prolyl-arginal (GYKI-14766), in a canine model of coronary artery thrombosis.

The antithrombotic activity of the tripeptide thrombin inhibitor, D-methyl-phenylalanyl-prolyl-arginal (GYKI-14766), was compared to heparin in a model of canine coronary artery thrombosis. Thrombogenesis was initiated by electrolytic injury of the intimal surface of the left circumflex coronary artery. Drug administration was started 15 min before initiation of intimal injury. Clotting times and ex vivo platelet aggregation were determined on citrated blood samples. Gingival template bleeding times were determined. Clotting times (thrombin time; activated partial thromboplastin time, APTT; prothrombin time, PT) increased in a dose-dependent manner with both anticoagulants. The two anticoagulants selectively inhibited thrombin-induced platelet aggregation. GYKI-14766 and heparin were found to delay thrombosis significantly when compared to vehicle-treated animals; minimum effective antithrombotic doses were 0.25 mg/kg/h and 80 U/kg + 30 U/kg/h, respectively. GYKI-14766 (0.25 mg/kg/h) had no effect on template bleeding time, APTT or PT. Heparin (80 U/kg + 30 U/kg/h), however, was associated with a 2.5- to 3.0-min increase in template bleeding time, a 1.8-fold and 1.7-fold increase in APTT and PT, respectively. Antithrombotic efficacy was achieved at doses of GYKI-14766 that did not affect APTT, PT or template bleeding time, whereas antithrombotic efficacy observed with heparin was associated with significant increases in APTT, PT and template bleeding time. These data demonstrate that the tripeptide thrombin inhibitor, GYKI-14766, could potentially prove to be a safer and more effective antithrombotic agent than heparin.

Animals↗

LY53857, a 5HT2 receptor antagonist, delays occlusion and inhibits platelet aggregation in a rabbit model of carotid artery occlusion.

The present study was designed to evaluate the effectiveness of the ergoline 5HT2 receptor antagonist, LY53857 in a rabbit model of vascular arterial occlusion. LY53857 (1 and 10 microM) inhibited serotonin amplified platelet aggregation responses to threshold concentrations of ADP in rabbit platelets in vitro. LY53857 (1 microM) not only inhibited the serotonin component of rabbit platelet aggregation, but also inhibited in vitro aggregation induced by ADP (48.7 +/- 16.7% inhibition), collagen (76.1 +/- 15.9% inhibition) and U46619 (65.2 +/- 12.3% inhibition). The effectiveness of this ergoline 5HT2 receptor antagonist in blocking aggregation to ADP, collagen and U46619 may be related to its ability to inhibit a serotonin component of platelet aggregation since rabbit platelets possess high concentrations of serotonin that may be released during aggregation produced by other agents. Based on the effectiveness of LY53857 to inhibit rabbit platelet aggregation, we explored the ability of LY53857 to extend the time to carotid artery occlusion in rabbits following electrical stimulation of the artery. Reproducible carotid artery occlusion was induced in rabbits by moderate stenosis coupled to arterial cross clamping, followed by electrical stimulation. With this procedure, occlusion occurred at 47.0 +/- 7 min (n = 30) after initiation of the electrical stimulation. Animals pretreated with LY53857 (50 to 500 micrograms/kg i.v.) showed a delay in the time to carotid artery occlusion (at 100 micrograms/kg i.v. occlusion time extended to 164 +/- 16 min). Furthermore, ex vivo platelet aggregation from animals treated with LY53857 (300 micrograms/kg i.v.) resulted in 40.5% inhibition of platelet aggregation in response to the combination of ADP (1 microM) and serotonin (1 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Two studies of menstrual synchrony: negative results.

In 1971 McClintock reported menstrual synchrony in pairs and groups of women who spent time together. The two studies reported herein, based on the methods and research design introduced by McClintock, fail to replicate her results. The first study is of a sample of 132 women who were sorority members or roommates of sorority members living on the campus of a large coeducational state university. The second study is of a sample of 24 women who were members of a cooperative house near the same university. In the subjects from both studies, the final mean onset absolute difference is greater than the initial mean onset absolute difference, and there are more nonsynchronous pairs of subjects than synchronous pairs. The sample from the sorority study was progressively reduced to exclude those subjects with irregular menstrual cycle lengths and those pairs in which one subject was taking oral contraceptives. Menstrual synchrony did not emerge in the reduced sample. Thus, whether or not menstrual synchrony occurs among women who spend time together should still be considered a hypothesis requiring further investigation.

Adolescent↗

Sustained release of isomazole from matrix tablets administered to dogs.

Isomazole matrix tablet formulations, with various concentrations of hydroxypropyl methylcellulose (HPMC) hydrogel, were prepared and tested for sustained-release activity. Sustained-release activity was determined by administering isomazole test formulations orally to conscious dogs, instrumented with an indwelling left ventricular pressure transducer, and monitoring cardiac inotropic changes for 12 h thereafter. The HPMC hydrogel incorporated into the tablets at a concentration of 20-30% did not significantly change the magnitude of inotropic response or duration of action. Increasing the HPMC concentration to 40 and 42.5% in the formulations decreased the peak LVdP/dt60 response (cardiac inotropic activity) to isomazole, increased the response duration, and maintained the area under the curve (AUC) of LVdP/dt60 versus time. Higher concentrations of HPMC decreased both LVdP/dt60 peak activity and AUC without producing a sustained response. A very narrow range of HPMC concentration in the matrix tablet is thus required to achieve isomazole sustained-release activity.

Administration, Oral↗

Male axillary secretions influence women's menstrual cycles: a critique.

W. B. Cutler et al. report in the December 1986 issue of Hormones and Behavior (20, 463-473), that women treated with axillary extract from male donors showed reduced variability in menstrual cycle lengths and a reduced proportion of aberrant cycles. The initial samples--seven subjects treated with the male extract and nine subjects treated with blank/ethanol--did not differ significantly in the frequency of aberrant and normal cycles. The cycles of four subjects who were having weekly coital activity were removed from the samples, since coital activity has been shown to be associated with normal-length cycles. The frequency differences of aberrant and normal cycles in the reduced extract and placebo samples were statistically significant. The experiment's conclusions are questionable because (1) the decision to remove the cycles of the four women who had weekly coital activity was not justified by the evidence from this experiment and (2) the researchers lacked an observed preexperimental data base from which to measure changes in the women's cycle lengths.

Female↗

The effects of various nutritional supplements on the growth, migration and differentiation of Xenopus laevis neural crest cells in vitro.

This study investigates the nutritional requirements of Xenopus laevis neural crest cells and melanophores developing in vitro. A comparison is made between the growth and differentiation of cells in serum-containing medium and a chemically defined, serum-free medium that we have designed. Our chemically defined medium is more efficient than serum-supplemented medium in promoting proliferation of these cells. Several supplements are required to enhance culture development. These include insulin, alpha-melanocyte stimulating hormone, somatotropin, luteotrophic hormone, linoleic acid, uridine, and putrescine. In addition, collagen and fibronectin provide the most conducive environment tested for cell migration and adhesion.

Animals↗

Female axillary secretions influence women's menstrual cycles: a critique.

Preti, Cutler, Garcia, Huggins, and Lawley report (1986, Horm. Behav. 20, 474-482) that women's menstrual cycles can be modulated with applications of female-derived secretions. An experimental sample of 10 women who reported that they had 29.5 +/- 3 day menstrual cycles was treated on a 22- to 25-day cycle with an extract of axillary secretions from a group of female donors. After two menstrual cycles, the mean absolute difference between the women's menses onsets and the treatment applications decreased significantly. A control sample of 9 women similarly treated with blank/ethanol showed no significant change. Reanalysis of the data indicates that four subjects in the extract sample synchronized with the extract cycles because of "errors" in the extract applications and another four synchronized as a result of experimental design, mathematical properties of cocycling menses onsets, and chance variations. After these factors are accounted for, no evidence suggests that the cycles of the subjects in the extract sample were modulated by the female-derived axillary secretion.

Axilla↗

Studies on cellular adhesion of Xenopus laevis melanophores: modulation of cell-cell and cell-substratum adhesion in vitro by endogenous Xenopus galactoside-binding lectin.

We have investigated cell-cell and cell-substratum adhesion of Xenopus laevis neural crest cells at various stages of melanophore differentiation. Single-cell suspensions were obtained by trypsinization and aggregated in a cell-cell adhesion assay. Unpigmented cells did not adhere while the rate of adhesion of melanophores correlated with the degree of melanization. Melanophore cell-cell adhesion decreased significantly in the presence of beta-galactosidase, which suggests that cell-surface galactose is involved. Beta-galactoside-binding lectin has been isolated and purified from embryos at the stage of neural crest migration. When added to aggregating cells smaller, looser clusters formed compared to controls. When lectin was added to cells in stationary culture to test cell-substratum adhesion, melanophores spread more smoothly and formed more regular spacing patterns. These results suggest that this lectin can modulate receptors used in cell-cell and cell-substratum adhesion of melanophores.

Animals↗

Acute myopathy in horses at grass in east and south east Scotland.

A myopathy of horses at grass in east and south east Scotland was recognised in the autumn and winter of 1984 and the spring of 1985. The clinical signs resembled those of paralytic myoglobinuria. Grossly increased creatine kinase activities and the passage of dark brown urine were consistent features. However, the horses were not in training, most of them died and the muscles affected were those of posture and respiration rather than movement. The condition may be unrelated to nutritional myopathy because all the cases had adequate levels of alpha-tocopherol although their selenium status varied from normal to deficient. The clinical and pathological findings in 12 cases are presented and the differential diagnosis and possible aetiologies discussed.

Acute Disease↗

Cell surface carbohydrate involvement in controlling the adhesion and morphology of neural crest cells and melanophores of Xenopus laevis.

Pieces of dorsal neural tube (stages 22-23) or late neural crest tissue (stages 24-26) of Xenopus laevis were cultured. Migratory cells moved out of explants to form an outgrowth of multipolar melanophores on the substratum. Treatment with beta-galactosidase (0.1-0.4 U/ml) to remove cell surface galactose was correlated with detachment of melanophores. In the presence of lower concentrations of this enzyme the shapes of these cells were converted to arborized, spidery morphologies and cell movement was inhibited. Unpigmented cells were affected more slowly. Neuraminidase treatment, to remove cell surface sialic acid and expose more galactose, only affected melanophores. These became increasingly spread on the substratum and cell overlap was observed. These results suggest that the relative amounts of galactose and sialic acid at the cell surface become increasingly important in controlling cell adhesion as X. laevis neural crest cells migrate and differentiate into melanophores.

Animals↗

Molecular basis for the in vitro and in vivo cardiotonic activities of AR-L100.

Imidazo[4,5-b]pyridines, such as AR-L57, AR-L100 and AR-L115 (Vardax), have been of interest as inotropic agents for the management of congestive heart failure. Although it has been presumed that their activities derive from inhibition of phosphodiesterase, it is now apparent that similar structural analogs possess surprisingly diverse pharmacologies and mechanisms of action. AR-L100 increased the contractile state of cat papillary muscles in a concentration-dependent manner; these effects were not blocked by either alpha, beta or H2-receptor antagonists. To determine whether the contractile responses resulted from intracellular cyclic AMP accumulation, the cardiotonic actions of AR-L100 were assessed in the presence of carbachol. Muscarinic receptor stimulation did not alter inotropic responses to AR-L100; in addition, AR-L100 did not potentiate the inotropic actions of isoproterenol. These results imply that cyclic AMP is not involved in the cardiac responses to this agent. AR-L100 inhibited Na+,K+-adenosine triphosphatase activity of either canine kidney or cardiac sarcolemmal vesicles. Inhibition of this enzyme paralleled inotropic responses in vitro; that is, in papillary muscle, the EC50 for contractility was 11.5 microM compared with an IC50 for inhibition of Na+,K+-adenosine triphosphatase of 8 microM. By contrast, the IC50 for inhibition of phosphodiesterase (isozyme III) was 280 microM. AR-L100 also inhibited sodium pump activity in intact cat papillary muscles. Concentrations of 30 and 100 microM AR-L100 resulted in 13 and 45% decreases in ouabain-sensitive 86Rb+ uptake determined at 3 Hz. In anesthetized dogs, AR-L100 increased contractility but did not alter either heart rate or mean arterial blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗