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Biomedical subjects

R Holt

Publications and source records attributed to R Holt.

At least 19 recordsLinked to original sources
PubMed2000

Tropisetron plus dexamethasone is more effective than tropisetron alone for the prevention of postoperative nausea and vomiting in children undergoing tonsillectomy.

The 5-HT3 antagonists are effective in reducing postoperative nausea and vomiting (PONV) associated with paediatric tonsillectomy. Although prophylactic tropisetron can reduce the incidence of PONV by half, the resulting level of over 40% is still unacceptably high. The aim of this study was to evaluate the effect of adding dexamethasone to tropisetron. In a blinded study, 59 children (mean age 6.1 years) were administered 0.1 mg.kg-1 up to 2 mg of tropisetron and 66 children (mean age 5.7 years) received the same dose of tropisetron plus 0.5 mg.kg-1 up to 8 mg of dexamethasone. Both drugs were given intravenously during induction of anaesthesia for tonsillectomy. During the inpatient stay of 24 h, the incidence of postoperative vomiting in the tropisetron alone group was 53% compared with 26% in the combination group (P=0.002, chi-squared). A significant reduction in nausea from 53% to 30% was also observed (P=0.02). Parents completed a daily diary for 5 days following discharge. Delayed vomiting occurred in 27% and 11% of the tropisetron and combination therapy groups, respectively (P=0.025) Sixteen percent and 9%, respectively, required medical attention (P=0.27). Tropisetron plus dexamethasone is more effective than tropisetron alone in reducing the incidence of PONV following paediatric tonsillectomy.

Adolescent↗
PubMed1998

Development of an immunoassay for monitoring the levels of ciprofloxacin in patient samples.

It has been traditional to measure drug concentrations using high pressure liquid chromatography (HPLC). While this method is highly accurate, it is time consuming and requires the use of appropriate standards for identification of the compound. In addition, identification and quantification of drugs from patient samples requires significant manipulation to remove protein. In contrast, enzyme-linked immunoassays (EIA) are able to assay samples with a high degree of specificity, and are able to process multiple samples at a time. In addition, serum proteins do not interfere with sample quantification and samples may be tested without significant preparation. We describe the development of an EIA for the detection of ciprofloxacin in serum and dialysate samples. The immunoassay is specific for ciprofloxacin and is sensitive for picogram amounts of the antibiotic.

Animals↗
PubMed1998

The role of disclosure in coping with HIV infection.

A qualitative investigation was conducted to explore the role of disclosure in HIV infection. Forty homosexual and bisexual men completed a short demographic questionnaire and participated in a one-to-one, semi-structured interview. The interview was designed to address a variety of personal, interpersonal and organizational issues related to their HIV status and participants were invited to talk about their personal experiences from immediately prior to their diagnosis to the time of the interview. The results from the interviews are presented in three sections: immediately post-diagnosis, asymptomatic phase and symptomatic/AIDS phases. The data revealed that disclosing one's HIV status was an acute and recurrent stressor. Immediately post-diagnosis, individuals were more likely to adopt a policy of non-disclosure and this provided them with an opportunity to come to terms with their diagnosis before having to contend with the reactions of others. After this phase, there was evidence that individuals increasingly used disclosure as a mechanism for coping with the disease. Disclosure of one's status was used to increase both practical and emotional support, share responsibility for sex and to facilitate self-acceptance of one's condition. The results from this investigation revealed that disclosure has a dual role in HIV infection acting as both a stressor and a mechanism by which individuals contend with their infection.

Acquired Immunodeficiency Syndrome↗
PubMed1998

An in vitro comparison of thermoplasticised gutta-percha obturation techniques with cold lateral condensation.

This study compared the apical sealing ability, obturation time and extrusion of gutta-percha and sealer when root canals were obturated using either cold lateral condensation or one of the three methods using thermoplasticised gutta-percha (Alpha Seal, Thermafil or JS Quick Fill) in vitro. One hundred and thirty-one root canals from 78 extracted human teeth were used; 116 canals were divided into five groups so that they were balanced with respect to prepared canal anatomy, and the remaining 15 canals were used as positive and negative controls. The canals in the first four groups were prepared with hand files using the step-down technique to a standard apical size and flare. The last group was prepared using engine-driven rotary nickel-titanium files (McSpadden) to a similar apical size and flare. One of the four obturating techniques was used to fill the canals in each of the first four groups. The fifth group was obturated using the Alpha Seal technique. The roots were immersed in india ink, demineralised and rendered transparent to assess the extent of maximum lincar dye penetration. The Alpha Seal groups had the highest number of specimens without any leakage. There was a significant difference in the proportions of specimens that did not leak when the Alpha Seal (P < 0.01) and cold lateral condensation groups (P < 0.05) were compared with JS Quick Fill. Cold lateral condensation had a higher proportion of specimens with leakage in canals with curvature greater than 20 degrees than in canals with curvatures less than 20 degrees (P < 0.05). The curvature of canals had no effect on the sealing ability of the other techniques. The method of canal preparation had no effect on the sealing ability of Alpha Seal. Alpha Seal, Thermafil and JS Quick Fill were significantly quicker to perform than cold lateral condensation.

Analysis of Variance↗
PubMed1997

Towards gene therapy of Hurler syndrome.

Allogeneic bone marrow transplantation is the most effective treatment for Hurler's syndrome. However, due to a lack of matched related donors and unacceptable morbidity of matched unrelated transplants, this therapy is not available to all patients. Therefore we have been developing an alternative approach based on transfer and expression of the normal gene in autologous bone marrow. A retroviral vector carrying the full length cDNA for alpha-L-iduronidase has been constructed and used to transduce bone marrow from patients with this disorder. A number of different gene transfer protocols have been assessed including the effect of intensive schedules of exposure of bone marrow to viral supernatant and the influence of growth factors. With these protocols we have demonstrated successful gene transfer into primitive CD34+ cells and subsequent enzyme expression in their maturing progeny. Also, using long-term bone marrow cultures, we have demonstrated high levels of enzyme expression sustained for several months. The efficiency of gene transfer has been assessed by PCR analysis of haemopoietic colonies as around 50%. No advantage has been demonstrated for the addition of growth factors or intensive viral exposure schedules. Indeed a possible disadvantage has been identified for the use of intensive transduction procedures. The enzyme is secreted into the medium and functional localisation has been demonstrated by reversal of the phenotypic effects of lysosomal storage in macrophages. This pre-clinical work forms the basis for a clinical trial of gene therapy for Hurler syndrome.

Bone Marrow Cells↗
PubMed1997

Serotonin levels as a function of age in Aplysia californica.

The neurotransmitter serotonin (5-HT) plays an important role in a number of behaviors in Aplysia californica some of which have been shown to vary with age. We were thus interested in examining the age-dependence of 5-HT in A. californica. Because animals of the same age can have very different weights, and weight alone is reliably known for wild-caught animals, we also examined the variation of 5-HT with weight. Serotonin was measured in the ring and abdominal ganglia combined, in lab-reared animals from 3 to 12 months post-hatch across a wide weight range. Serotonin increased rapidly from 4 to 6 months, and more slowly from 6 to 13 months. Serotonin scaled by soluble ganglion protein increased from 3 to 6-7 months, reached a maximum, and then decreased again. Serotonin, but not scaled 5-HT, increased significantly with weight across the whole weight range. Animals of the same weight, but different ages, had different 5-HT levels, as did young animals of the same age but different weight. Serotonin varied significantly with both age and weight, with the age-dependence being the more significant.

Aging↗
PubMed1997

Looming vulnerability to spreading contamination in subclinical OCD.

The present study examined the hypothesis, stimulated by the looming vulnerability model of anxiety (Riskind, in press, Behaviour Research and Therapy), that subclinical OCD is associated with a subjective sense of looming vulnerability. One-hundred and four undergraduates rated vignettes of common, everyday situations involving exposure to possible dirt, germs, or contamination. Participants in a subclinical obsessional group had a far higher sense of looming vulnerability to spreading contamination than did those in a control group. Results verified that the subjective sense of looming vulnerability still had separate, distinct and significant contributions to fear-of-contamination symptoms, with the effects of cognitive appraisals of other aspects of threat (such as probability of harm, or lack of control) removed. In contrast, these other cognitive appraisals had no significant associations with symptoms that proved to be independent of the subjective sense of looming vulnerability. A path analysis further explored the dependency of these other cognitive appraisals on looming vulnerability. This analysis found that part of the effects of the subjective sense of looming vulnerability on fears may be indirect and mediated via correlated effects of other cognitive appraisals.

Adult↗
PubMed1996

Inhaled nitric oxide increases coronary artery patency after thrombolysis.

BACKGROUND: Nitric oxide (NO) and nitrosovasodilators that release NO inhibit platelet aggregation. The antithrombotic effect of intravenously infused nitrosovasodilators is usually accompanied by systemic vasodilation. Inhaled NO is a pulmonary vasodilator that does not produce systemic hemodynamic effects. This study examines the antithrombotic effect of inhaled NO in a canine model of platelet-mediated coronary artery reocclusion after thrombolysis. METHODS AND RESULTS: In 25 anesthetized dogs, a segment of the left anterior descending coronary artery was traumatized and a high-grade stenosis created. Thrombus was injected at this site, and tissue plasminogen activator was administered, producing cyclic flow variations (CFVs) in 24 of 25 dogs. CFV frequency was unchanged in dogs not breathing NO but decreased by 35 +/- 9% (P < .05) and 53 +/- 7% (P < .01) while dogs breathed 20 and 80 parts per million (ppm) NO, respectively. The coronary artery patency ratio (fraction of time during which the coronary artery was patent; CAPR) was unchanged in dogs not treated with NO but increased from 51 +/- 7% to 64 +/- 8% while breathing 20 ppm NO (P < .01) and from 49 +/- 3% to 75 +/- 7% while breathing 80 ppm NO (P < .01). The increased CAPR during 80 ppm NO administration persisted during a 45-minute posttreatment period (70 +/- 7%, P < .05 versus baseline). NO inhalation did not change systemic hemodynamics. In a pharmacological model of coronary vasoconstriction, inhaled NO did not reverse the effect of the thromboxane A2 agonist U-46619. In vitro ADP-induced platelet aggregation was inhibited by NO gas. CONCLUSIONS: Inhaled NO at concentrations of 20 and 80 ppm increases coronary patency and decreases CFV frequency in a canine model of platelet-mediated coronary reocclusion after thrombolysis without producing systemic hemodynamic effects.

Adenosine Diphosphate↗
PubMed1996

The effect of domestic water filters on water fluoride content.

The effect of filtration on water fluoride level was investigated in a study using commercially available filters. Testing was carried out in London (low fluoride), Braintree (optimum fluoride, naturally occurring) and Birmingham (optimum fluoride, artificially adjusted). It was found that none of the filters removed fluoride. In Birmingham, but not in either Braintree or London, there was a small, clinically insignificant increase in fluoride levels with filtration using two of the five filters. It is concluded that the water filtration systems tested will not affect the advantage offered by optimum water fluoride levels. Fluoride dietary supplements should not be prescribed for children living in optimal fluoride areas, irrespective of whether they use household filters.

Analysis of Variance↗
PubMed1996

Long-term in vitro correction of alpha-L-iduronidase deficiency (Hurler syndrome) in human bone marrow.

Allogeneic bone marrow transplantation is the most effective treatment for Hurler syndrome but, since this therapy is not available to all patients, we have considered an alternative approach based on transfer and expression of the normal gene in autologous bone marrow. A retroviral vector carrying the full-length cDNA for alpha-L-iduronidase has been constructed and used to transduce bone marrow from patients with this disorder. Various gene-transfer protocols have been assessed including the effect of intensive schedules of exposure of bone marrow to viral supernatant and the influence of growth factors. With these protocols, we have demonstrated successful gene transfer into primitive CD34+ cells and subsequent enzyme expression in their maturing progeny. Also, by using long-term bone marrow cultures, we have demonstrated high levels of enzyme expression sustained for several months. The efficiency of gene transfer has been assessed by PCR analysis of hemopoietic colonies as 25-56%. No advantage has been demonstrated for the addition of growth factors or intensive viral exposure schedules. The enzyme is secreted into the medium and functional localization has been demonstrated by reversal of the phenotypic effects of lysosomal storage in macrophages. This work suggests that retroviral gene transfer into human bone marrow may offer the prospect for gene therapy of Hurler syndrome in young patients without a matched sibling donor.

Antigens, CD34↗
PubMed1995

Costs and management of urinary incontinence in long-term care.

The three aims of the study were (1) to assess the impact and cost of urinary incontinence in long-term care, (2) to determine whether 24-hour incontinence monitoring provides information that improves management, and (3) to ascertain whether costs (nursing time and laundry) could be reduced. The setting was two 24-bed long-term care units in an urban hospital. The research was conducted in three stages. During the initial stage, the impact of incontinence was measured on each unit. Impact was defined as total number of incontinent episodes, nursing time spent changing these patients, and laundry costs, measured during a 7-day period on each unit. After this phase of the investigation, individualized 24-hour incontinence monitoring, followed by recommendations and implementation of care plan, was carried out on one unit. No monitoring or recommendations for care were completed on the other unit, which served as a control. During the third phase of the study, the number of incontinent episodes, nursing time, and laundry costs were again measured on both units. Initially (58%) of residents (24/48) were incontinent, representing 859 episodes of urinary leakage each week that required 45 hours of nursing time to change clothing, containment devices, and bed linens. The direct costs of the nursing time and laundry, expressed in Canadian dollars were $8.60/day per incontinent resident. After 24-hour monitoring of 10 residents one on unit, suggestions were made for various incontinence management programs. An unexpected but simple recommendation was a change to a better containment system for urinary leakage. When impact was measured, a 13% reduction in the number of incontinent episodes was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

A chimeric murine/human antibody Fab fragment directed against the platelet GPIIb/IIIa receptor enhances and sustains arterial thrombolysis with recombinant tissue-type plasminogen activator in baboons.

Inhibition of the platelet glycoprotein (GP) IIb/IIIa receptor with the murine monoclonal antibody 7E3 abolishes ex vivo platelet aggregation, reduces thrombogenicity, and sustains arterial recanalization with recombinant tissue-type plasminogen activator (rt-PA). A chimeric murine/human Fab fragment of 7E3 (c7E3-Fab) has a markedly reduced immunogenicity, but its potency as an adjunct for thrombolysis with rt-PA has not been evaluated. The effects of a single intravenous bolus injection of aspirin (17 mg/kg) or c7E3-Fab (0.45 mg/kg) on thrombolysis and reocclusion induced with rt-PA were studied in groups of six baboons with femoral arterial thrombosis and superimposed high-grade stenosis. This dose of c7E3-Fab blocked 96 +/- 1% of the platelet GPIIb/IIIa receptors and abolished ADP-induced platelet aggregation. Bolus intravenous injections of rt-PA (0.25 mg/kg) were repeated at 15-minute intervals until reperfusion occurred (maximum of four injections). In the aspirin group, reperfusion was obtained within 51 +/- 16 minutes (mean +/- SD) but was rapidly followed by reocclusion within 6 +/- 9 minutes and by cyclic reflow and reocclusion. In the c7E3-Fab group, reperfusion was obtained within 25 +/- 8 minutes (P < .01 versus aspirin group) and was associated with a delayed reocclusion of 63 +/- 63 minutes (P < .05 versus aspirin group). Template bleeding times remained unchanged in the aspirin/rt-PA group but were markedly prolonged (to > 30 minutes) in the c7E3-Fab/rt-PA group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗