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Biomedical subjects

A S Walker

Publications and source records attributed to A S Walker.

At least 19 recordsLinked to original sources
PubMed2004

Selective antegrade cerebral perfusion attenuates brain metabolic deficit in aortic arch surgery: a prospective randomized trial.

BACKGROUND: Aortic arch surgery has a high incidence of brain injury. This may in part be caused by a cerebral metabolic deficit observed after hypothermic circulatory arrest (HCA). We hypothesized that selective antegrade cerebral perfusion (SACP) would attenuate this phenomenon. METHODS AND RESULTS: In a prospective randomized trial, 42 adult patients were allocated to either HCA (22) or SACP. HCA occurred at a nasopharyngeal temperature of 15 degrees C and SACP at a corporeal temperature of 25 degrees C with cerebral perfusion at 15 degrees C. Paired arterial and jugular venous samples were taken before and after arrest. Continuous transcranial Doppler monitoring of middle cerebral artery velocity (MCAV) was performed. Neuropsychometric testing was performed preoperatively and at 6 and 12 weeks postoperatively. There were 3 hospital deaths (7.1%), 2 strokes (4.8%), and 6 episodes of transient neurological deficit (14.3%). From before to after arrest, jugular bulb pO2 changed by -21.67 mm Hg (26.4) in the HCA group versus +2.27 mm Hg (18.8) in the SACP group (P=0.007). Oxygen extraction changed by +1.7 mL/dL (1.3) in the HCA group versus -1 mL/dL (2.4) in the SACP group (P<0.001). MCAV increased by 6.25 cm/s (9.1) in the HCA group and 19.2 cm/s (10.1) in the SACP group (P=0.001). Incidence of neuropsychometric deficit at 6 weeks was 6/12 (50%) in HCA patients and 8/10 (80%) in SACP patients (P=0.2), and at 12 weeks was 6/16 (38%) in HCA patients and 4/11 (36%) in SACP patients (P=1). CONCLUSIONS: SACP attenuates the metabolic changes seen after HCA. Further studies are required to assess optimal perfusion conditions and clinical outcome.

Adult↗
PubMed2004

Highly active antiretroviral therapy started in infants under 3 months of age: 72-week follow-up for CD4 cell count, viral load and drug resistance outcome.

OBJECTIVE: To assess the feasibility and impact of highly active antiretroviral therapy (HAART) started in vertically HIV-1-infected infants less than 3 months of age. DESIGN: A multicentre, phase I/II, non-randomized, open-label study (PENTA 7). METHODS: Adverse events, plasma HIV-1 RNA, CD4 cell counts, CD4 cell percentage (CD4%) and clinical progression were recorded at baseline and prospectively to 72 weeks in order to assess the toxicity, tolerability and efficacy of a combination of stavudine, didanosine and nelfinavir. Selection of genotypic resistance was also investigated. RESULTS: Twenty infants, of whom only three had Centers for Disease Control and Prevention stage B, initiated HAART at median age 2.5 months (range, 0.9-4.7) with median HIV-1 RNA concentration 5.5 log10 copies/ml (range, 3.2-6.8) and CD4% 33% (range, 11-66). Median follow-up was 96 weeks (range, 60-144). At week 72, 11 infants were still taking the original treatment. Few adverse events were reported related to treatment, all minor and causing treatment interruption in only three infants. No AIDS-defining events occurred; one child died of non-HIV-related causes (prematurity). All but two had CD4% > 25% at 72 weeks; however, 14 infants had virological failure and six acquired resistance mutations. CONCLUSIONS: Early treatment with stavudine, didanosine and nelfinavir was well tolerated and associated with good clinical and immunological outcomes at week 72. However, a high rate of virological failure with emergence of genotypic resistance is of great concern. More palatable drug combinations for infants and closer drug monitoring are required.

Antiretroviral Therapy, Highly Active↗
PubMed2003

The relationship between HIV seroconversion illness, HIV test interval and time to AIDS in a seroconverter cohort.

Seroconversion illness is known to be associated with more rapid HIV disease progression. However, symptoms are often subjective and prone to recall bias. We describe symptoms reported as seroconversion illness and examine the relationship between illness, HIV test interval (time between antibody-negative and anibody-positive test dates) and the effect of both on time to AIDS from seroconversion. We used a Cox model, adjusting for age, sex, exposure group and year of estimated seroconversion. Of 1820 individuals, information on seroconversion illness was available for 1244 of whom 423 (34%) reported symptomatic seroconversion. Persons with a short test interval (< or = 2 months) were significantly more likely to report an illness than people with a longer interval (OR 6.76, 95% CI 4.75-9.62). Time to AIDS was significantly faster (P = 0.01) in those with a short test interval. The HIV test interval is a useful replacement for information on seroconversion illness in studies of HIV disease progression.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Poor sensitivity and consistency of microscopy in the diagnosis of low grade non-gonococcal urethritis.

OBJECTIVES: To determine the reliability of the diagnosis of non-gonococcal urethritis (NGU), and the variation between and within microscopists, from urethral smears at a large London genitourinary medicine clinic. METHODS: A senior microscopist (SM) preselected 60 Gram stained urethral smear slides, 20 negative (<5 polymorphs/hpf), 20 low grade NGU (5-20 p/hpf), and 20 high grade NGU (>20 p/hpf). Ten experienced microscopists, blinded to these initial grades, examined all slides giving each a polymorph score. After relabelling and randomly changing their order, the slides were re-examined by the same microscopists. Finally, the SM determined whether the study had resulted in loss of cells from any of the slides. The SM's initial grading and the consensus among microscopists provide two gold standards for analysis. RESULTS: Nine low grade and five high grade slides were removed from analysis because of loss of cells. By SM standard, considering microscopists' readings as simply non-NGU (<5 p/hpf) or NGU (>or=5 p/hpf), 97% from negative slides were correct (variation 93-100 across microscopists), 68% from low grade slides (45-95), and 94% from high grade slides (83-100). Consistency between repeat readings by the same microscopist was 96% for negatives, 75% for low grade and 89% for high grade slides. Results were similar by consensus standard. CONCLUSIONS: There was considerable variation between and within microscopists in the diagnosis of NGU. Sensitivity was strongly related to grade of urethritis, with an appreciable proportion of low grade urethritis falsely diagnosed as negative. With increasing attendances for sexual health screening, a false positive rate of only 3% may lead to many false diagnoses.

Humans↗
PubMed2001

Age as a determinant of survival in HIV infection.

Age is a major determinant of mortality for many diseases including HIV infection, yet the effect of age is rarely studied directly. In this article, we review what is known about the effect of age at seroconversion on HIV disease progression and survival prior to the widespread use of HAART before describing appropriate methods for adjusting for background mortality in more detail. We then investigate the impact of HAART on the effect of age at seroconversion on mortality and consider the estimation of the age effect in seroprevalent cohorts with regard to lack of knowledge of the true age at infection. Finally, we discuss mechanisms by which age at seroconversion might impact on disease progression and death. Throughout, we use published results by the Collaborative Group on AIDS Incubation and HIV Survival (CGAIHS), and published results and data from the Concerted Action on SeroConversion to AIDS and Death in Europe (CASCADE) for illustration.

Adult↗
PubMed2000

Analysis of multivariate failure-time data from HIV clinical trials.

We illustrate the use of marginal methods for the analysis of multivariate failure-time data using a large trial in HIV infection in which the composite endpoint of AIDS or death incorporates more than 20 events with varying severity. Multivariate failure-time methods are required to investigate whether treatment delays development of new AIDS events. AIDS events can be grouped and treatment effects estimated using only the first event to occur in each group for each individual. Alternatively, all events can be included by fitting a separate baseline hazard for development of each event, and restricting treatment effects to be common within groups of events. In either case, model-based or minimum-variance estimates of the overall effect of treatment can be constructed. The covariance matrix for the treatment-effect estimates can be used in multiple testing procedures. Results from the Delta trial suggest that combination antiretroviral therapy with AZT plus either ddI or ddC may delay progression to more severe AIDS events compared to AZT monotherapy. These late events are generally untreatable and prophylaxis is not available. Trials are not generally powered to detect treatment effects on individual events making up a composite endpoint, and therefore all analyses are exploratory rather than providing definitive evidence. However, marginal multivariate models provide an easily available approach for modeling the effect of covariates on multiple disease processes, and allow the likely effects of treatment to be presented in a manner which is easily understood. They can be used in a variety of ways to explore different patterns of treatment effects and are also useful for testing multiple hypotheses regarding treatment effects on several different composite endpoints.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Markers of HIV infection in the Concorde trial. Concorde Co-ordinating Committee.

The Concorde trial compared immediate (Imm) with deferred (Def) AZT monotherapy in asymptomatic HIV-positive participants. Haematological and immunological markers and weight were measured throughout, and correlated with clinical endpoints. Markers associated with disease progression (CD4 lymphocyte count and percentage, platelets, p24 antigen and beta 2 microglobulin favoured Imm: those associated with toxicity (haemoglobin, neutrophils and white cell count) favoured Def. CD8 and total lymphocyte count did not differ significantly between groups. In multivariate analysis, the combination of baseline CD4, p24 antigen and beta 2m was the best baseline predictor of disease. Including change in CD4 and beta 2m at 12 weeks, or changes over follow-up in these markers significantly improved the fit. Markers were also incorporated into the definition of 'clinical' endpoints. Hazard ratio estimates from end-points that included CD4 < 50 and CD4 < 25 were closest to those for AIDS or death alone, but added very few extra events. Use of other landmark CD4 counts (100 or greater) or relative decreases in counts (25% or more) increased the number of events, but overestimated the effect of immediate AZT. Although AZT had a beneficial effect on the surrogate markers of efficacy evaluated, these changes did not predict clinical outcome, nor could the markers be usefully incorporated into an endpoint definition.

Anti-HIV Agents↗
PubMed1984

Development of knowledge of visual-tactual affordances of substance.

Infants of 12 months were familiarized in the dark with an object of either a hard or an elastic (spongy) substance. Following 60 sec of manipulation, a visual preference test was given with simultaneous presentation of 2 films of identical objects, 1 moving in a pattern characteristic of a rigid object and 1 moving in a pattern characteristic of an elastic object. Infants handled the 2 substances differently in an appropriate manner and looked preferentially with more and longer first looks to the type of substance familiarized. A replication of this experiment with familiarization in the light yielded comparable results. A third experiment with 1-month-old infants allowed them to mouth objects of either a hard or a soft substance for haptic familiarization and then tested looking preferences with real objects moving rigidly or deforming. These infants looked longer at the object moving in a manner characteristic of the novel substance. The results, together, suggest that quite young infants detect intermodal invariants specifying some substances and perceive the affordance of the substance.

Child Development↗
PubMed1983

Conditions for the chemical and physical inactivation of the K. Fu. strain of the agent of Creutzfeldt-Jakob disease.

The unusual resistance of the "unconventional viruses" to inactivation by the commonly used disinfectants has led to a high degree of apprehension regarding patients with any form of dementia. The rapid adaptation of a newly acquired isolate of the agent of Creutzfeldt-Jakob Disease (CJD) to mice made possible this large scale study of its heat and chemical stability. The agent showed a decrease in titer of approximately two logs following incubation at 80 degrees C for 30 minutes with no additional loss at 80 degrees C for up to 500 minutes. There was greater than a three log decrease in titer at 100 degrees C for 30 minutes and temperatures of 115 degrees and 130 degrees C completely inactivated the agent. Treatment with sodium hypochlorite at three concentrations (0.33 per cent, 0.66 per cent and 1.31 per cent) showed inactivation of greater than 99 per cent at each. Crude agent preparations were not inactivated by sodium dodecylsulfate at detergent to protein ratios up to 4:1. These results suggest that those hospital supplies which resist autoclaving may be adequately disinfected by autoclaving for at least 30 minutes. Treatment of surfaces with solutions of sodium hypochlorite (household bleach) at concentrations of 15 to 25 per cent is also effective. Detergent treatment of contaminated surfaces or materials is inadequate for proper decontamination.

Animals↗
PubMed1980

Detection of elasticity as an invariant property of objects by young infants.

Three-month-old infants were habituated to two different motions of deformation, presented 'live' with an object of sponge rubber. After habituation, one-third of the subjects was presented with a third deforming motion; one-third was presented with a rigid motion of the same object; and the other third was presented with a continuation of the habituation sequence. The group presented with a rigid motion dishabituated, exhibiting a sharp increase in looking time. The other two groups showed little or no increase. These results suggest that infants perceive elasticity of substance, in contrast to rigidity, as an invariant property of an object over different deforming motions.

Elasticity↗
PubMedDate not supplied

Co-trimoxazole as prophylaxis against opportunistic infections in HIV-infected Zambian children (CHAP): a double-blind randomised placebo-controlled trial.

BACKGROUND: No trials of co-trimoxazole (trimethoprim-sulfamethoxazole) prophylaxis for HIV-infected adults or children have been done in areas with high levels of bacterial resistance to this antibiotic. We aimed to assess the efficacy of daily co-trimoxazole in such an area. METHODS: We did a double-blind randomised placebo-controlled trial in children aged 1-14 years with clinical features of HIV infection in Zambia. Primary outcomes were mortality and adverse events possibly related to treatment. Analysis was by intention to treat. FINDINGS: In October, 2003, the data and safety monitoring committee recommended early stopping of the trial. 541 children had been randomly assigned; seven were subsequently identified as HIV negative and excluded. After median follow-up of 19 months, 74 (28%) children in the co-trimoxazole group and 112 (42%) in the placebo group had died (hazard ratio [HR] 0.57 [95% CI 0.43-0.77], p=0.0002). This benefit applied in children followed up beyond 12 months (n=320, HR 0.48 [0.27-0.84], test for heterogeneity p=0.60) and across all ages (test for heterogeneity p=0.82) and baseline CD4 counts (test for heterogeneity p=0.36). 16 (6%) children in the co-trimoxazole group had grade 3 or 4 adverse events compared with 18 (7%) in the placebo group. These events included rash (one placebo), and a neutrophil count on one occasion less than 0.5x10(9)/L (16 [6%] co-trimoxazole vs seven [3%] placebo, p=0.06). Pneumocystis carinii was identified by immunofluorescence in only one (placebo) of 73 nasopharyngeal aspirates from children with pneumonia. INTERPRETATION: Our results suggest that children of all ages with clinical features of HIV infection should receive co-trimoxazole prophylaxis in resource-poor settings, irrespective of local resistance to this drug.

AIDS-Related Opportunistic Infections↗