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Biomedical subjects

P Wright

Publications and source records attributed to P Wright.

At least 55 records · Page 3Linked to original sources
PubMed2000

A phase II study of two HIV type 1 envelope vaccines, comparing their immunogenicity in populations at risk for acquiring HIV type 1 infection. AIDS Vaccine Evaluation Group.

Several immunogens induce HIV-specific neutralization and in vitro lymphoproliferation in adults at low HIV-1 risk, but responses in persons at high HIV-1 risk are not known. We performed a multicenter, double-blinded, adjuvant-controlled trial with two gp120 vaccines in 296 HIV-1-uninfected volunteers, including 176 reporting higher HIV-1 risk activities. The immunogens were remarkably well tolerated. After three immunizations, 210 of 241 vaccinees (87%) developed neutralizing antibodies, which persisted in 59% after 2 years. The injection drug users receiving SF-2/gp120 had decreased antibody responses relative to the lower risk groups. Envelope-specific lymphoproliferation peaked after two immunizations, and 54% of vaccinees mounted a DTH reaction to gp120 after 4 years. In summary, these immunogens have low adverse reactogenicity and induce durable antibody and T cell responses to the prototype strains. Unexpected differences in antibody responses among diverse HIV-1 risk strata lend support to the conduct of expanded phase II trials in populations other than low-risk volunteers.

AIDS Vaccines↗
PubMed2000

Route choices, anticipated forgetting, and interface design for on-line reference documents.

Preference and usability are imperfectly correlated when choice among procedures depends on anticipating cognitive difficulties. Navigation choices were explored by offering 2 routes through an on-line price catalog. The harder route never varied, but interface features of the easier route varied across readers. In Experiment 1, readers chose the easier route (82% trials) when it was visually salient but otherwise preferred the harder route from the active window. This suggested that visual factors influenced decisions. Experiment 2 equated visual factors, but choice of the easier route fell significantly when it needed an activation click. Navigating the harder route increased readers' use of an on-line notebook (i.e., people more often anticipated forgetting prices while reading). People choose easier procedures unless interface design miscues anticipated effort. Thus, usability evaluation needs to include factors influencing choices among methods.

Adult↗
PubMed2000

Text entry on handheld computers by older users.

Small pocket computers offer great potential in workplaces where mobility is needed to collect data or access reference information while carrying out tasks such as maintenance or customer support. This paper reports on three studies examining the hypothesis that data entry by older workers is easier when the pocket computer has a physical keyboard, albeit a small one, rather than a touch-screen keyboard. Using a counter-balanced, within-subjects design the accuracy and speed with which adults over 55 years of age could make or modify short text entries was measured for both kinds of pocket computer. The keyboard computer was the Hewlett Packard 360LX (HP), but the touch-screen computers varied across studies (experiment 1: Apple Newton and PalmPilot; experiment 2: Philips Nino; experiment 3: Casio E10). All studies showed significant decrements in accuracy and speed when entering text via the touch-screen. Across studies, most participants preferred using the HP's small physical keyboard. Even after additional practice with the touch screen (experiments 2 and 3) many entries still contained errors. Experiment 3 showed that younger people were faster but not more accurate than older people at using the touch-screen keyboard. It is concluded that satisfactory text entry on palm-size computers awaits improvements to the touch-screen keyboard or alternative input methods such as handwriting or voice. Interface developments that assist older people typically benefit younger users too.

Aged↗
PubMed2000

Changing pattern of organ dysfunction in early human sepsis is related to mortality.

OBJECTIVE: We examined the pattern of organ system dysfunction, the evolution of this pattern over time, and the relationship of these features to mortality in patients who had sepsis syndrome. DESIGN: Prospective, multicenter, observational study. SETTING: Intensive care units in tertiary referral teaching hospitals. PATIENTS: A total of 287 patients who had sepsis syndrome were prospectively identified in intensive care units. MATERIALS AND MEASUREMENTS: Cardiovascular, pulmonary, neurologic, coagulation, renal, and hepatic dysfunction were assessed at onset and on day 3 of sepsis syndrome. Organ dysfunction was classified as normal, mild, moderate, severe, and extreme dysfunction. We calculated the occurrence rate and associated 30-day mortality rate of organ dysfunction at the onset of sepsis syndrome. We then measured the change in organ dysfunction from onset to day 3 of sepsis syndrome and determined, for individual organ systems, the associated 30-day mortality rate. RESULTS: At the onset of sepsis syndrome, clinically significant pulmonary dysfunction was the most common organ failure, but was not related to 30-day mortality. Clinically significant cardiovascular, neurologic, coagulation, renal, and hepatic dysfunction were less common at the onset of sepsis syndrome but were significantly associated with the 30-day mortality rate. Worsening neurologic, coagulation, and renal dysfunction from onset to day 3 of sepsis syndrome were associated with significantly higher 30-day mortality than with improvement or no change in organ dysfunction. CONCLUSIONS: Increased mortality rate in sepsis syndrome is associated with a pattern characterized by failure of nonpulmonary organ systems and, in particular, worsening neurologic, coagulation, and renal dysfunction over the first 3 days. Although initial pulmonary dysfunction is common in patients with sepsis syndrome, it is not associated with an increased mortality rate.

Aged↗
PubMed2000

Ones that got away.

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Allergy and Immunology↗
PubMed2000

A method for separation of phosphatidylcholine, triacylglycerol, non-esterified fatty acids and cholesterol esters from plasma by solid-phase extraction.

Efficient isolation of individual lipid classes is a critical step in the analysis of plasma and lipoprotein fatty acid compositions. Whilst good separations of total lipid extracts are possible by TLC, this method is time consuming and a major rate-limiting step when processing large numbers of specimens. A method for rapid separation of phosphatidylcholine (PC), non-esterified fatty acids (NEFA), cholesterol ester (CE) and triacylglycerol (TAG) from total plasma lipid extracts by solid-phase extraction (SPE) using aminopropyl silica columns has been developed and validated. Following initial separation of polar and neutral lipids, individual classes were isolated by application of solvents with increasing polarity. Recoveries for combined plasma extraction with chloroform-methanol and SPE were (%): PC 74.2 (SD 7.5), NEFA 73.6 (SD 8.3), CE 84.9 (SD 4.9), and TAG 86.8 (SD 4.9), which were significantly greater for TAG and NEFA than by TLC Both GC-flame ionisation detector and GC-MS analysis of fatty acid methyl esters demonstrated that there was no cross-contamination between lipid classes. Measurements of repeatability of fatty acid composition for TAG, PC, CE and NEFA fractions showed similar CV for each fatty acid. The magnitude of the CV appeared to be related inversely to the fractional fatty acid concentration, and was greatest at concentrations of less than 1 g/100 g total fatty acids. There was no evidence of selective elution of individual fatty acid or CE species. In conclusion, this method represents an efficient, rapid alternative to TLC for isolation of these lipid classes from plasma.

Cholesterol Esters↗
PubMed2000

"Saves" project.

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Aged↗
PubMed1999

Developments in international standardization.

Trade in animals and animal products has reached global proportions and so too has the threat of infectious diseases of veterinary importance. The Manual of Standards for Diagnostic Tests and Vaccines, published by the Office International des Epizooties (OIE), contains chapters on infectious diseases that may cause various degrees of socio-economic, public health, and/or zoo-sanitary consequence. These chapters cover the major diseases of cattle, sheep, goats, horses, pigs, poultry, lagomorphs and bees. A number of factors are considered when qualifying animals and animal products for international trade including epidemiological, clinical and testing parameters. Of particular note and relevance is a strong international movement to standardize the test methods and reference reagents in order to promote harmonization of testing and facilitation of trade. There is message here that is directed to those of us involved in the development and application of test methods for infectious disease diagnosis. Serological test methods have been and still remain the mainstay of diagnostic methods prescribed for trade. More than ever, there is a need to observe and apply international guidelines for the development and validation of serological test methods. There is also a need to develop international standard reagents for use in the calibration of test methods and the production of national and working standards. In the future, veterinary diagnostic testing laboratories involved in trade may also require a form of international accreditation unique to their specialty. This presentation describes the current developments in international standardization of test methods and reference reagents.

Animal Diseases↗
PubMed1999

Spatial and seasonal variation in heavy metals in the sediments and biota of two adjacent estuaries, the Orwell and the Stour, in eastern England.

A study was made of the concentrations of the elements As, Cd, Cu, Hg, Mn, Ni, Pb and Zn in the sediments and biota of two adjacent estuaries, the Orwell and Stour, in eastern England. The Orwell Estuary, with its urbanized head, was more contaminated with heavy metals than the Stour Estuary. Generally, in both estuaries, concentrations of metals were highest towards the head and the mouth. Saltmarsh sediments accumulated higher concentrations of most metals than mudflat sediments. Metal concentrations in the biota showed marked interspecific differences; Mytilus edulis had higher concentrations of Cd, Littorina littorea higher concentrations of Cu and Mn and Arenicola marina higher concentrations of Hg. Invertebrates from the Orwell had higher metal concentrations than those from the Stour. Algae had generally lower levels of metals than invertebrates. Metal concentrations were greatest and more variable in the top 10 cm of sediment. Metals were at greatest concentrations in winter and lowest in summer in sediments, algae and invertebrates. Mercury concentration increased with size in the three invertebrate species studied, but Cd and Zn generally were at higher concentrations in younger animals. Comparisons of sediments with average shale values indicated anthropogenic enrichment with several metals but it was considered that only Pb, at some sites, and possibly Hg posed potential threats to the ecology of the estuaries.

Animals↗
PubMed1999

Eicosanoid biosynthesis in an advanced deuterostomate invertebrate, the sea squirt (Ciona intestinalis).

The eicosanoid generating potential of tunic, branchial basket, intestine, ovary and tadpole larvae from the sea squirt, Ciona intestinalis, was examined using a combination of reverse phase high performance liquid chromatography, gas chromatography-mass spectrometry and enzyme immunoassay. All organs examined synthesized the lipoxygenase products 12-hydroxyeicosapentaenoic acid (12-HEPE) and 8-HEPE implying that both 8- and 12-lipoxygenase activity are widely distributed in this species. In addition, tunic and branchial basket generated significant amounts of 8,15-diHEPE and smaller amounts of 8,15-dihydroxyeicosatetraenoic acid (8,15-diHETE), while tunic alone generated small amounts of conjugated tetraene-containing material with a UV chromophore and mass ion characteristic of a lipoxin-like compound. The broad range lipoxygenase inhibitors, esculetin and nordihydroguaiaretic acid, both caused a significant dose dependent inhibition of 12-HEPE and 8,15-diHEPE biosynthesis in tunic, while the specific 5-lipoxygenase inhibitor, REV-5901, and the specific 5-lipoxygenase activating protein inhibitor, MK-866, had no observable effect on the lipoxygenase profile of this tissue. Tunic, branchial basket, intestine and ovary all generated significant amounts of prostaglandin (PG) E and PGF immunoreactive material and smaller amounts of thromboxane B immunoreactive material as measured by enzyme immunoassay. The non-specific cyclooxygenase (COX) inhibitor, indomethacin, the selective COX-1 inhibitors, resveratrol and valerylsalicylate, and the specific COX-2 inhibitors, NS-398, etolodac and DFU (5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl-2(5H)-furanone) all caused a significant dose dependent inhibition of the biosynthesis of PGE immunoreactive material. However, the specific COX-2 inhibitors were most effective, perhaps implying that a COX-2-like enzyme may be present in this species.

Animals↗
PubMed1999

Pitfalls in the application of enzyme-linked immunoassays for the detection of circulating trypanosomal antigens in serum samples.

The experimental infection of two goats with Trypanosoma vivax trypanosomes provided samples for analysis using parasitology techniques and antigen-detection enzyme-linked immunosorbent assays (ELISAs) for T. vivax, T. congolense and T. brucei. Clinical, parasitological and serological findings were monitored during the course of infection to identify problems in the application of these ELISAs. The data clearly showed that the ELISAs examined were entirely unsuitable for the reliable detection of trypanosomal antigen. Consequently, research strategies pertinent to the development of a new generation of both antigen and antibody ELISAs are outlined considering the problems encountered. These were (1) the reactivity of the reagents; (2) the specificity of the reagents; (3) the nature of the test sample, e.g. the compartmentalisation of trypanosomes between plasma, serum and red blood cells; (4) possible interference with the ELISA through immune complexing; and (5) the biology of the host/trypanosome relationship to gain an understanding of fluctuations in trypanosomes in the systemic circulation.

Animals↗
PubMed1999

Failure to respond to treatment with typical antipsychotics is not associated with CYP2D6 ultrarapid hydroxylation.

AIMS: To investigate whether or not there is a correlation between failure to respond to typical antipsychotics and CYP2D6 ultrarapid metaboliser status. METHODS: CYP2D6 phenotype (metaboliser status) was assigned following genotyping for gene duplication, as well as for the CYP2D6*3, CYP2D6*4, and CYP2D6*5 null alleles in 235 treatment-refractory patients and 73 nonrefractory patients. RESULTS: Four (1.7%) of the 235 treatment-refractory subjects were positive on the duplication assay, but, of these, two were found to represent duplications of a null allele (CYP2D6*4 ), therefore leaving only two (0.85%) positive for duplication of a wild type allele (ultrarapid metabolisers). Three (4.1%) of the nonrefractory subjects had a genotype consistent with ultrarapid metaboliser status. Fisher's exact test gave a two-tailed P value of 0.091, i.e. a trend towards an excess of ultrarapid metabolisers in the nonrefractory group, which was in the opposite direction to that predicted by our hypothesis. CONCLUSIONS: Although the results show a trend towards an excess of ultrarapid metabolisers in the nonrefractory group, the percentages in the two groups of patients are both within the range for ultrarapid metabolisers in Caucasian populations. Our data are not consistent with ultrarapid metaboliser status being a major cause of failure to respond to typical antipsychotics.

Alleles↗
PubMed1999

The development of a collaborative stroke training programme for nurses.

The effectiveness of multidisciplinary stroke rehabilitation may be enhanced by nurses and therapists adopting a single consistent approach to the positioning and mobilizing of patients. As patients can spend as little as 4% of the waking day receiving 'therapy' there is considerable potential for a more dynamic nursing intervention, which may contribute to improving patient care. We aimed to investigate whether physiotherapists could step back from direct patient treatment in order to participate in a structured training programme for nurses involved with patients recovering from stroke on an established elderly care rehabilitation ward in a district general hospital. Qualitative methods were used within a participatory action research framework to describe the development process and content of the training programme. Nursing staff, physiotherapists and their respective managers were interviewed to identify perceived training needs. This informed the structure and content of the training course and allowed insight into interprofessional working.

Attitude of Health Personnel↗
PubMed1999

Adenovirus-mediated TNF-alpha gene transfer induces significant tumor regression in mice.

Recombinant adenovirus vectors are highly efficient at in vitro and in vivo gene delivery. The in vitro infection of a mouse colon adenocarcinoma cell line MCA-26 with the adenovirus AdV-LacZ can reach a maximal 75% of infectivity at an MOI of 1000. Intratumoral injection of AdV-LacZ (2X10(9) pfu) resulted in substantial gene transfer in nearly 70% of MCA-26 tumors. After the in vitro infection of AdV-TNF-alpha, infected MCA-26 cells showed significant secretion of TNF-alpha (45 ng/ml/10(6) cells) in tissue culture. The secretion peaks at day 2 and is diminished at day 4 following the viral infection. Infected MCA-26 tumor cells secreting TNF-alpha significantly reduced their tumorigenicity in syngeneic BALB/c mice. In mice bearing small tumors, intratumoral injection of 2X10(9) pfu of AdV-TNF-alpha virus with a repeated booster treatment resulted in complete regression of three tumors and significant diminution of the other two with a mean tumor-weight of 0.16 g; this is in contrast to 0.85 and 1.62 g for tumors injected with the control AdV-pLpA and PBS respectively (p < 0.01). Mice with complete tumor regression further developed protective immunity against the second challenge of MCA-26 inoculation. In mice bearing large tumors, this treatment also caused significant inhibition of tumor growth with a mean tumor weight of 0.65 g vis-a-vis 3.05 g for tumors injected with the control AdV-pLpA. On the contrary, in mice bearing large tumors, the treatment of tumors with pCI-TNF-alpha delivered by the gene gun did not induce significant tumor inhibition. These results indicate that the adenoviral delivery of TNF-alpha gene is more efficient than the particle-mediated gene gun device, and that adenovirus-mediated cytokine gene therapy may be a useful approach in the clinical management of human solid tumors.

Adenocarcinoma↗
PubMed1999

Effects of a physiotherapist-led stroke training programme for nurses.

AIM: to assess the effects of a physiotherapist-led stroke training programme for nurses working in a rehabilitation ward on clinical practice and patient outcome. METHOD: before and after group comparison with outcome assessment by observational and quantitative methods. Non-participant observation before and after the 5-month training programme recorded patient position, transfers and contact with nursing staff. Quantitative assessments of disability, satisfaction and mood were made at baseline, discharge and 4 months after stroke onset. We also noted selected stroke complications, rehabilitation ward length of stay and discharge destination. RESULTS: there was a significant improvement in the number of observed 'good' transfers of patients undertaken by nurses (chi2 = 9.13, df = 1, P = 0.003) but the training programme had no impact on the time the patients spent in 'poor' positions. There was no significant difference between the two groups for Barthel index scores at discharge and at 4 months. Neither was there any significant difference in the Hospital Anxiety and Depression scale, occurrence of secondary complications, length of stay or the Patient and Carer Satisfaction Questionnaires. CONCLUSION: within the limitations of the research design adopted, some improvements in clinical practice were reported but there were no significant differences in patient outcome. The training programme required no additional resources and should be replicable in most district general hospitals.

Aged↗
PubMed1999

Effects of ibuprofen on the physiology and survival of hypothermic sepsis. Ibuprofen in Sepsis Study Group.

OBJECTIVES: The objective was to compare the clinical and physiologic characteristics of febrile septic patients with hypothermic septic patients; and to examine plasma levels of cytokines tumor necrosis factor alpha (TNF-alpha and interleukin 6 (IL-6) and the lipid mediators thromboxane B2 (TxB2) and prostacyclin in hypothermic septic patients in comparison with febrile patients. Most importantly, we wanted to report the effect of ibuprofen treatment on vital signs, organ failure, and mortality in hypothermic sepsis. SETTING: The study was performed in the intensive care units (ICUs) of seven clinical centers in the United States and Canada. PATIENTS: Four hundred fifty-five patients admitted to the ICU who met defined criteria for severe sepsis and were suspected of having a serious infection. INTERVENTION: Ibuprofen at a dose of 10 mg/kg (maximum 800 mg) was administered intravenously over 30 to 60 mins every 6 hrs for eight doses vs. placebo (glycine buffer vehicle). MEASUREMENTS AND MAIN RESULTS: Forty-four (10%) septic patients met criteria for hypothermia and 409 were febrile. The mortality rate was significantly higher in hypothermic patients, 70% vs. 35% for febrile patients. At study entry, urinary metabolites of TxB2, prostacyclin, and serum levels of TNF-alpha and IL-6 were significantly elevated in hypothermic patients compared with febrile patients. In hypothermic patients treated with ibuprofen, there was a trend toward an increased number of days free of major organ system failures and a significant reduction in the 30-day mortality rate from 90% (18/20 placebo-treated patients) to 54% (13/24 ibuprofen-treated patients). CONCLUSIONS: Hypothermic sepsis has an incidence of approximately 10% and an untreated mortality twice that of severe sepsis presenting with fever. When compared with febrile patients, the hypothermic group has an amplified response with respect to cytokines TNF-alpha and IL-6 and lipid mediators TxB2 and prostacyclin. Treatment with ibuprofen may decrease mortality in this select group of septic patients.

Anti-Inflammatory Agents, Non-Steroidal↗