Search PubMed⌕ Search

Biomedical subjects

P Robinson

Publications and source records attributed to P Robinson.

At least 91 records · Page 5Linked to original sources

Platelet glycoprotein IIb/IIIa blockade with tirofiban: effect on aggregation caused by P256, an antibody to human IIb/IIIa receptors.

AIMS: P256 is a divalent antibody which aggregates human platelets by interaction with glycoprotein (GP) IIb/IIIa receptors. We investigated the effect of tirofiban, an antagonist of the GP IIb/IIIa receptor, on P256-mediated platelet aggregation. METHODS: Responses to agonists were measured turbidometrically at 37 degrees C in stirred citrated platelet-rich plasma from venous blood samples from healthy human volunteers. Inhibitory effects were determined by comparison with aggregation to the same concentration of agonist in a vehicle treated sample. RESULTS: Tirofiban inhibited a near maximally effective dose of P256 (10-7 mol l-1 ) with an IC50 of 9. 3x10-8 mol l-1. Tirofiban (10-7 mol l-1 ) inhibited responses to arachidonic acid, U46619 and P256 similarly, whereas aspirin (1. 1x10-4 mol l-1 ) inhibited arachidonic acid more effectively than P256 (P<0.007 by anova ). CONCLUSIONS: Tirofiban potently and selectively inhibits P256-stimulated aggregation of human platelets.

Abciximab↗

Pancreatic enzyme replacement therapy in cystic fibrosis: Australian guidelines. Pediatric Gastroenterological Society and the Dietitians Association of Australia.

Pancreatic enzyme replacement therapy (PERT) is a major factor associated with achieving optimum growth and nutritional status in cystic fibrosis (CF) patients with pancreatic insufficiency and consequent malabsorption. Currently in Australian CF clinics policies for the usage of PERT vary considerably. This paper highlights the current issues related to fat absorption and use of PERT in CF. It also provides evidence to support the recommendation of a PERT dose based on a standard ratio of lipase units per gram of dietary fat consumed for individual patients. A consistent approach to PERT doses will facilitate identification of patients whose PERT intake increases their risk of fibrosing colonopathy and for whom gastroenterological review is warranted. Recent reports indicate that PERT intake can be reduced with a secondary improvement in growth and nutrition status as a consequence of increased dietetic input. These Australian guidelines for the judicious use of PERT in CF should lead not only to a refinement in nutritional management of patients with CF but should also facilitate an improvement in compliance with therapy due to sophistication in patient education materials. The Australian guidelines for the use of PERT in CF if correctly applied, will also provide patients and their families with a better understanding of the relationship between PERT and nutritional status.

Adolescent↗

Effect of unilateral breathing exercises on regional lung ventilation.

We investigated the effect of a unilateral thoracic expansion exercise (TEE), a breathing manoeuvre used by physiotherapists, on regional lung ventilation. Nine trained physiotherapists aged 22-37 years completed the study. Technegas lung ventilation scans were used to determine the effect of a right unilateral TEE performed when sitting. This was compared with a maximal deep breath. Total radioactivity in each lung was determined. Each lung was sectioned into three equal zones (upper, middle and lower) and the ratio of radioactivity for each of the corresponding lung zones calculated. Ventilation was preferentially distributed to the right lung in all participants during both breathing manoeuvres. The mean (+/- S.E.M.) radioactivity ratios (right/left lung) were greater during a unilateral TEE (1.17 +/- 0.02) than during a deep breath (1.07 +/- 0.01). Seven participants achieved significantly greater ventilation to the right middle (1.15 +/- 0.03, P = 0.02) and lower zones (1.34 +/- 0.03, P = 0.02) during a unilateral TEE than to the corresponding zones on the left; this was evident soon after the initiation of the breath. The findings of this study show that relative regional ventilation to the ipsilateral lung can be increased during a unilateral TEE in trained individuals.

Adult↗

Improvement of nebulised antibiotic delivery in cystic fibrosis.

AIM: To investigate deposition patterns and to assess the delivery rate of two nebuliser systems in children with cystic fibrosis (CF). METHODS: Thirty three children with CF on regular treatment with nebulised antibiotics had radioisotope scans performed using technetium-99m labelled aerosol antibiotic generated by a Ventstream nebuliser (median mass diameter (MMD), 3.3 microm; delivery rate, 0. 075 ml/min) under conditions similar to their routine home practice. The inhomogeneity of the images was scored on a 1-10 rating scale (a low score indicating even distribution of the antibiotic), and stomach deposition was measured as a percentage of overall deposition. Twenty patients had a repeat scan using an Optimist nebuliser (MMD, 1.8 microm; delivery rate, 0.02 ml/min). RESULTS: The mean inhomogeneity scores were 5.4 in the Ventstream group and 3. 5 in the Optimist group. Mean stomach deposition was 17.3% in the 33 patients using the Ventstream nebuliser. There was an inverse relation between height and stomach deposition (r = 0.69). In the 20 patients who had both nebulisers, the mean percentages of stomach deposition for the Ventstream and Optimist nebulisers were 11.8% and 1.6%, respectively. The Ventstream nebuliser delivered antibiotic at an average 2.8 times faster rate than the Optimist nebuliser. IMPLICATIONS: A smaller particle size results in a more homogenous distribution of the antibiotic in the lungs with decreased stomach deposition. This should not be seen as a recommendation to use the Optimist nebuliser because more antibiotic was delivered to most parts of the lung with the Ventstream because of its increased delivery rate.

Administration, Inhalation↗

Early use of inhaled nedocromil sodium in children following an acute episode of asthma.

BACKGROUND: Current guidelines on the treatment of childhood asthma recommend the introduction of an anti-inflammatory drug in children who have persistent symptoms and require regular treatment with a bronchodilator. The efficacy and safety of inhaled nedocromil sodium (Tilade Mint aerosol) administered using a Fisonair spacer at a dose of 4 mg three times daily was compared with placebo in the treatment of asthmatic children aged 6-12 years who are symptomatic and recovering from an acute exacerbation of asthma. METHODS: A group comparative, double blind, placebo controlled trial was performed in children who were recovering from an acute episode of asthma following treatment in the emergency department of the hospital or in children referred from their general practitioner following a wheezing episode and documented evidence of at least two previous episodes of wheezing. A two week baseline period on existing bronchodilator treatment was followed by a 12 week treatment period on either nedocromil sodium (2 mg/puff) or placebo. Both treatments were administered using a Fisonair spacer at a dose of two puffs three times daily. Changes from baseline values in daytime asthma and night time asthma symptom scores, usage of rescue bronchodilators, mean peak expiratory flow (PEF) recorded twice daily on diary cards, patients' opinion of treatment, and withdrawals due to treatment failure were measured during the primary treatment period (last six weeks of treatment). RESULTS: One hundred and forty two children aged 6-12 years entered the baseline period. Sixty three were withdrawn due to failure to meet the entry criteria (18) or the criteria for asthma symptom severity (15) or reversibility (9), because they developed uncontrolled asthma (2), because they took disallowed treatment (2), or for other non-trial related reasons (17). Seventy nine patients (46 boys) of mean age 8. 8 years entered the treatment period. There were significant differences in the changes from baseline values during the last six weeks of treatment in favour of nedocromil sodium compared with placebo in the primary variables of daytime asthma and night time asthma, morning and evening PEF, and the usage of rescue inhaled bronchodilators; 53% of patients reported nedocromil sodium to be very or moderately effective compared with 44% placebo. Improvement in asthma symptoms, PEF, and reduction in use of rescue bronchodilators did not reach statistical significance until after six weeks of treatment. Twenty two patients were withdrawn or dropped out during the treatment phase, 12 due to uncontrolled asthma or persistence of asthma symptoms, four due to suspected adverse drug reactions (nedocromil sodium 3 (headaches 2, angio-oedema/urticaria 1), placebo 1(persistent cough)), and six due to non-treatment related reasons. Seventy one adverse events were reported by 27 patients in the nedocromil group and 75 by 30 patients in the placebo group. CONCLUSIONS: Asthma symptoms, use of bronchodilators, and lung function can be improved significantly in children recovering from an acute exacerbation of asthma or wheeze and currently receiving treatment with bronchodilators alone by the addition of inhaled nedocromil sodium at a dose of 4 mg three times daily administered using a Fisonair holding chamber.

Acute Disease↗

Increased airway smooth muscle in sudden infant death syndrome.

The underlying pathophysiological mechanism behind death in the sudden infant death syndrome (SIDS) is uncertain. Although infants dying of SIDS frequently have a postmortem examination performed, no specific diagnostic pathology in any organ system has been identified. Previous theories relating to the cause of death in SIDS have included increased lower airway closure. We examined the airway morphometry of 57 infants who died of SIDS and compared these findings with those obtained from 21 age-matched infants who had died of non-SIDS causes. Airway wall dimensions, epithelial thickness, and the area of smooth muscle within the airway wall were measured. Airways from infants who died of SIDS showed a significantly higher proportion of airway smooth muscle than control airways when corrected for age and sex (p < 0.01). There was no significant difference between the groups for wall thickness or epithelial thickness. Increased airway smooth muscle in infants who have died of SIDS may contribute to excessive airway narrowing, raising the possibility that the cause of death in this condition is related to abnormalities in lower airway function.

Airway Resistance↗

Estimates of the virological benefit of antiretroviral therapy are both assay- and analysis-dependent.

OBJECTIVE: To assess the potential discrepancies in reported changes in plasma viral load (PVL) depending on how values below the detection limit of the assay are handled in the data analysis phase of a randomized controlled clinical trial. DESIGN: Data from a recently completed clinical trial comparing combinations of zidovudine, didanosine and nevirapine were analysed. In this trial, PVL was measured using an assay with a lower quantification limit of 400 HIV-1 RNA copies/ml initially. All PVL values less than 500 copies/ml were retested with a more sensitive assay with a lower quantification limit of 20 copies/ml. METHODS: Several summary measures for assessing change in PVL were calculated using three different methods to adjust for PVL values less than the quantification limit of the assay. The differences between these measures were evaluated. RESULTS: We found that the magnitude of the discrepancy between summary measures used to report changes in PVL depended on the proportion of subjects with PVL less than the quantification limit of the assay, how those observations were handled in the data analysis, and the relative difference between the quantification limits of the conventional and more sensitive assay. CONCLUSION: The lack of consensus in reporting of PVL data in the literature makes the interpretation of published trial results difficult. In the absence of agreement on the most appropriate summary measure of PVL data, we recommend that all summaries include information on the quantification limit of the assay used, the proportion of observations at or below the quantification limit and how these observations were handled in the data analysis.

Analysis of Variance↗

Suppression of plasma viral load below 20 copies/ml is required to achieve a long-term response to therapy.

BACKGROUND: Current guidelines state that the goal of antiretroviral therapy for HIV-infected individuals is to suppress plasma viral load (pVL) to below 400 copies/ml. METHODS: Predictors of achieving and maintaining pVL suppression were examined in a randomized trial of combinations of zidovudine, nevirapine and didanosine in patients with CD4+ T cell counts of between 200 and 600 x 10(6) cells/l who were naive to antiretroviral therapy and AIDS-free at enrolment. RESULTS: One hundred and four patients had pVL > 500 copies/ml at baseline and a pVL nadir below 500 copies/ml. Of these, 77 patients experienced an increase in pVL above 500 copies/ml. The median number of days of pVL suppression to below 500 copies/ml was 285 (42) for patients with pVL nadir < or = (>) 20 copies/ml (P = 00.0001). The relative risk of an increase in pVL above 500 copies/ml associated with a pVL nadir below 20 copies/ml was 0.11 (P = 0.0001). The relative risks of an increase in pVL above 5000 copies/ml associated with a pVL nadir below 20 copies/ml or between 20 and 400 copies/ml were 0.05 [95% confidence interval (CI), 0.02-0.12] and 0.37 (95% CI, 0.23-0.61) respectively, compared with individuals with a pVL nadir > 400 copies/ml. Individuals with a pVL nadir < or = 20 copies/ml were at a significantly lower risk of virologic failure than individuals with a pVL nadir of between 21 and 400 copies/ml (P = 0.0001). CONCLUSIONS: Our results demonstrate that suppression of pVL below 20 copies/ml is necessary to achieve a long-term antiretroviral response. Our data support the need for a revision of current therapeutic guidelines for the management of HIV infection.

Anti-HIV Agents↗

A randomized, double-blind trial comparing combinations of nevirapine, didanosine, and zidovudine for HIV-infected patients: the INCAS Trial. Italy, The Netherlands, Canada and Australia Study.

CONTEXT: Current guidelines recommend that individuals infected with the human immunodeficiency virus type 1 (HIV-1) be treated using combinations of antiretroviral agents to achieve sustained suppression of viral replication as measured by the plasma HIV-1 RNA assay, in the hopes of achieving prolonged remission of the disease. However, until recently, many drug combinations have not led to sustained suppression of HIV-1 RNA. OBJECTIVE: To compare the virologic effects of various combinations of nevirapine, didanosine, and zidovudine. DESIGN: Double-blind, controlled, randomized trial. SETTING: University-affiliated ambulatory research clinics in Italy, the Netherlands, Canada and Australia (INCAS). PATIENTS: Antiretroviral therapy-naive adults free of the acquired immunodeficiency syndrome with CD4 cell counts between 0.20 and 0.60x10(9)/L (200-600/microL). INTERVENTION: Patients received zidovudine plus nevirapine (plus didanosine placebo), zidovudine plus didanosine (plus nevirapine placebo), or zidovudine plus didanosine plus nevirapine. MAIN OUTCOME MEASURE: Plasma HIV-1 RNA. RESULTS: Of the 153 enrolled patients, 151 were evaluable. At week 8, plasma HIV-1 RNA levels had decreased by log 2.18, 1.55, and 0.90 in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively (P<.05). The proportions of patients with plasma HIV-1 RNA levels below 20 copies per milliliter at week 52 were 51%, 12%, and 0% in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively (P<.001). Viral amplification was attempted in 59 patients at 6 months. Viral isolation was unsuccessful in 19 (79%) of 24, 10 (53%) of 19, and 5 (31%) of 16 patients in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively. Among patients from whom virus could be amplified, resistance to nevirapine was found in all 11 patients receiving zidovudine plus nevirapine and in all 5 patients receiving triple drug therapy. Rates of disease progression or death were 23% (11/47), 25% (13/53), and 12% (6/51) for the zidovudine plus nevirapine, zidovudine plus didanosine, and triple drug therapy groups, respectively (P=.08). CONCLUSIONS: Triple drug therapy with zidovudine, didanosine, and nevirapine led to a substantially greater and sustained decrease in plasma viral load than the 2-drug regimens studied. Our results also suggest that suppression of viral replication, as demonstrated by a decrease in the plasma HIV-1 RNA load below the level of quantitation of the most sensitive test available, may at least forestall the development of resistance.

Adult↗

CTAP and MRI.

Explore the source record for details and available documents.

Humans↗

The polymerase chain reaction: from functional genomics to high-school practical classes.

After a decade of intensive use as an in vitro alternative to cloning DNA, PCR is now well established as the default method for DNA and RNA analysis. Recent developments have consolidated this position by the introduction of more robust formats, improvements in thermal cyclers and labelling and detection methods. The trend is towards increasing automation, although comparatively few diagnostic kits based on PCR are in wide use. At the same time the applications of PCR are being extended with modifications such as long, accurate PCR and arrayed oligonucleotides or expressed sequences.

Chromosome Mapping↗