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Biomedical subjects

S G Edwards

Publications and source records attributed to S G Edwards.

At least 19 recordsLinked to original sources

Improved survival for HIV infected patients with severe Pneumocystis jirovecii pneumonia is independent of highly active antiretroviral therapy.

BACKGROUND: Despite a decline in incidence of Pneumocystis jirovecii pneumonia (PCP), severe PCP continues to be a common cause of admission to the intensive care unit (ICU) where mortality remains high. A study was undertaken to examine the outcome from intensive care for patients with PCP and to identify prognostic factors. METHODS: A retrospective cohort study was conducted of HIV infected adults admitted to a university affiliated hospital ICU between November 1990 and October 2005. Case note review collected information on demographic variables, use of prophylaxis and highly active antiretroviral therapy (HAART), and hospital course. The main outcome was 1 month mortality, either on the ICU or in hospital. RESULTS: Fifty nine patients were admitted to the ICU on 60 occasions. Thirty four patients (57%) required mechanical ventilation. Overall mortality was 53%. No patient received HAART before or during ICU admission. Multivariate analysis showed that the factors associated with mortality were the year of diagnosis (before mid 1996 (mortality 71%) compared with later (mortality 34%; p = 0.008)), age (p = 0.016), and the need for mechanical ventilation and/or development of pneumothorax (p = 0.031). Mortality was not associated with sex, ethnicity, prior receipt of sulpha prophylaxis, haemoglobin, serum albumin, CD4 count, PaO2, A-aO2 gradient, co-pathology in bronchoscopic lavage fluid, medical co-morbidity, APACHE II score, or duration of mechanical ventilation. CONCLUSIONS: Observed improved outcomes from severe PCP for patients admitted to the ICU occurred in the absence of intervention with HAART and probably reflect general improvements in ICU management of respiratory failure and ARDS rather than improvements in the management of PCP.

AIDS-Related Opportunistic Infections↗

A formative evaluation of the potential role of nurse practitioners in a central London HIV outpatient clinic.

In-house audit demonstrated that 49% (173/352) of patients attending routine HIV outpatient care are asymptomatic and have needs that could potentially be met by other health care professionals. We therefore evaluated the potential development and acceptability of nurse practitioner roles in contributing to HIV outpatient care. Data were collected through 26 consultation observations, 25 patient interviews, 2 patient focus groups, 22 provider interviews and 8 provider focus groups. Service users were key members of the evaluation team. With increasing HIV incidence and the change in focus of doctor-patient consultations from acute to chronic disease management, there are concerns about the sustainability of easily available routine HIV outpatient appointments using the same model of care that has prevailed over the past 20 years. Nurse practitioner models of care were considered acceptable for asymptomatic patients, including those who do not have complex issues related to highly active antiretroviral therapy (HAART). Key considerations for the role include training, supervision, referral pathways, and a clear understanding of the limitations of nursing practice. There is an emphasis on the need to consider 'new ways of working' throughout the service, rather than merely substituting or transferring clinical roles between professionals. Funding pending, nurse practitioner roles are planned for implementation in late 2004. Evaluation will determine impact on service utilization, health and economic outcomes.

Ambulatory Care↗

Behavioural predictors of subsequent hepatitis C diagnosis in a UK clinic sample of HIV positive men who have sex with men.

OBJECTIVE: To explore the associations between self reported high risk sexual behaviours and subsequent diagnosis with hepatitis C virus (HCV) infection. METHODS: The Sex, Health and Anti-Retrovirals Project (SHARP) was a cross sectional study of sexual behaviour in HIV positive, men who have sex with men (MSM) attending a London outpatient clinic. From July 1999 to August 2000 participants completed a computer assisted self interview questionnaire (CASI) on recent sexual behaviour, recreational drug use, and detailed reporting of the last two sexual episodes involving different partners. Results were combined with routine clinic data and subsequent testing for HCV up to 21 April 2005. A new HCV diagnosis was defined as anti-HCV antibody seroconversion or positive HCV RNA following a previous negative. Incident rate ratios (IRR) were calculated using Poisson regression in Stata (version 9). Men contributed time at risk from interview until either their diagnosis or their last negative test result. RESULTS: Of the 422 men who completed questionnaires, 308 (73%) had sufficient clinical and HCV testing data available for analysis. Incident HCV infection was identified in 11 men. Unprotected anal intercourse, more than 30 sex partners in the past year, higher numbers of new anal sex partners, rimming (oro-anal sex), fisting, use of sex toys, and intranasal recreational drug use were associated with HCV. In multivariate analysis only fisting remained associated with HCV (adjusted IRR 6.27, p = 0.005). CONCLUSIONS: In this study of HIV positive MSM, fisting is strongly associated with HCV infection. Where individuals report high risk sexual behaviours, clinicians should offer appropriate testing for HCV infection.

Adult↗

Thrombotic thrombocytopaenic purpura in HIV-infected patients.

Thrombotic thrombocytopaenic purpura (TTP) results from deficiency of von Willebrand factor-cleaving protease (vWF-cp) activity. Eight HIV-infected patients presented with TTP, representing 12.5% of all TTP treated at this centre. In four patients presentation with TTP revealed underlying HIV infection, the other four patients were previously known to be HIV infected, with plasma exchange and highly active antiretroviral therapy (HAART) all recovered. Normalization of vWF-cp activity was associated with recovery. Relapse occurred in two patients who discontinued HAART against medical advice, suggesting that HIV has a causal role in this condition. Given the clear benefit from HAART in addition to plasma exchange, these data suggest that all patients presenting with TTP should undergo HIV testing.

Antiretroviral Therapy, Highly Active↗

Diagnostic utility of bone marrow sampling in HIV-infected patients since the advent of highly active antiretroviral therapy.

We investigated the diagnostic value of bone marrow (BM) sampling in investigation of HIV-infected patients presenting to a major London HIV treatment centre between 1999 and 2004. One hundred and fourteen consecutive patients underwent 130 BM samplings. The majority of BM aspirates were normal or showed non-diagnostic changes; microscopy revealed lymphoma in one and mycobacterial infection in two. Subsequent culture identified mycobacterial infection in nine samples. BM trephine had a diagnostic yield of 26% in patients with fever and cytopaenia (including mycobacteriosis in 14%, lymphoma in 6%, Castleman disease in 3% and "drug effect" in 3%), a yield of 20% in patients with fever, but no cytopaenia (mycobacteriosis in each case), and a yield of 19% in patients with cytopaenia in the absence of fever (lymphoma in 5% and "drug effect" in 14%). In investigation/staging of lymphoma, the diagnostic yield was 36%. The overall yield from BM sampling was 30% in patients receiving highly active antiretroviral therapy (HAART) and 23% in those not receiving HAART. In this study, BM sampling was of most diagnostic value in HIV-infected patients where fever and cytopaenia coexisted in the absence of localizing signs of infection, and in the staging/investigation of lymphoma. BM sampling had less diagnostic value in the investigation of fever without cytopaenia or cytopaenia without fever.

AIDS-Related Opportunistic Infections↗

Overcoming subjectivity in assessing facial lipoatrophy: is there a role for three-dimensional laser scans?

BACKGROUND: Prevalence and incidence rates of lipodystrophy vary widely and frequently rely upon self- and/or clinician reports. Currently no validated assessment tool for facial lipoatrophy is available. AIMS AND OBJECTIVES: To illustrate that assessment of the severity of facial lipoatrophy by patients and clinicians is subjective. To evaluate the reproducibility of facial three-dimensional surface laser scans. METHODS: Twenty-three HIV-positive men were recruited from an inner London HIV outpatient clinic in September 2001. CD4 count, viral load, antiretroviral history and body mass index were recorded. Patients and clinicians independently assessed the severity of facial lipoatrophy on a four-point scale and the level agreement was measured. Seventeen of the 23 patients (73.9%) underwent two scans 1 week apart, which were then superimposed. The volume difference (mm3) and mean difference (mm) between the scans for five regions of the face were measured and compared with the self-reported grade of facial lipoatrophy. RESULTS: For each pair of clinicians (P=0.03, 0.005 and 0.0002, respectively), and for one patient-clinician pair (P=0.004), there was a significant systematic difference between the two sets of gradings of facial lipoatrophy. The level of disagreement was generally higher for patients reporting facial lipoatrophy (n=17) compared to those not reporting it (n=6). The mean volume difference and mean difference between any region were within 200 mm3 and 0.25 mm, respectively. Reproducibility was unaffected by the self-reported grade of facial lipoatrophy. CONCLUSIONS: Assessment of the severity of facial lipoatrophy by patients and clinicians is subjective. Three-dimensional facial laser scans are reproducible and may provide an objective tool for monitoring changes in facial lipoatrophy.

Adult↗

Polymyositis masquerading as mitochondrial toxicity.

A 66 year old HIV infected male heavy smoker presented with arthralgia, myalgia, and weight loss which was originally ascribed to nucleoside induced mitochondrial toxicity. Despite withdrawal of antiretroviral therapy a proximal myopathy developed. Further investigation excluded malignancy. Polymyositis was diagnosed on muscle biopsy. The patient recovered completely with oral prednisolone. This case highlights the importance of muscle biopsy in HIV infected patients whose myopathy persists despite withdrawal of antiretroviral therapy and the need for thorough investigation of non-specific symptoms in HIV infected patients who are receiving antiretroviral therapy.

Aged↗

Cognitive correlates of supratentorial atrophy on MRI in multiple sclerosis.

OBJECTIVES: We aimed to investigate associations between neuropsychological indices and normalized volumes of supratentorial structures, and the area of the corpus callosum. MATERIALS AND METHODS: We studied 40 patients with clinically definite MS, using 3D-acquired MRI (MPRAGE, Magnetization Prepared Rapid Acquisition Gradient Echo) and stereology. Subjects underwent a neuropsychological battery interrogating multiple cognitive domains, from which a global Cognitive Index Score (CIS) was derived. RESULTS: White matter volumes were significantly correlated with CIS (rho= -0.59, P<0.0001) and with many of the individual cognitive tests. CIS was also significantly correlated with the corpus callosal area (rho= -0.49, P<0.002). Grey matter volumes did not significantly correlate with any cognitive test. CONCLUSIONS: These volume/function relationships presumably reflect the effects of subcortical axonal and myelin loss on the neural networks that subserve cognition. If serial MRI volume estimations can index accumulating cognitive deficits, this simple technique may be useful in therapeutic trials.

Adult↗

Mode of antagonism of Brevibacillus brevis against Botrytis cinerea in vitro.

AIMS: To assess the activity of Brevibacillus brevis (formerly Bacillus brevis) Nagano and the antibiotic it produces, gramicidin S, against the plant pathogen Botrytis cinerea. METHODS AND RESULTS: Germination and growth of Bot. cinerea were assessed in the presence of B. brevis or gramicidin S in liquid media, on solid media and on leaf sections of Chinese cabbage. Germination was 10-fold more sensitive to gramicidin S than growth. Inhibition of Bot. cinerea was greater in liquid media compared with on solid media. Activity of gramicidin S against Bot. cinerea on leaf sections was much lower than in vitro. In vitro inhibition of Bot. cinerea by B. brevis Nagano was similar to equivalent levels of gramicidin. CONCLUSIONS: Antibiosis, via gramicidin S, is the mode of antagonism exhibited by B. brevis Nagano against Bot. cinerea in vitro. SIGNIFICANCE AND IMPACT OF THE STUDY: The mode of antagonism of B. brevis against Bot. cinerea was elucidated. The differing activity of gramicidin S against Bot. Cinerea in vitro and on leaf sections indicates one mechanism by which biocontrol activity may differ between laboratory and field conditions.

Antibiosis↗

Experience of nevirapine use in a London cohort of HIV-infected pregnant women.

OBJECTIVE: To describe the experience of four London HIV centres prescribing nevirapine (NVP) to HIV-1 infected pregnant women with respect to immunological and virological response, tolerability and pregnancy outcome. METHODS: We identified all HIV-1-infected women who received NVP as part of a triple antiretroviral regimen during pregnancy between January 1997 and September 1999. Laboratory results, clinical events, side-effects and pregnancy outcome were abstracted using a standardized proforma from the medical records. RESULTS: Forty-six women were identified, 85% of whom were black African. At initiation of NVP, the median age was 29 years and the median baseline CD4 cell count and viral load were 242 cells/microL and 4.15 log10 copies/mL, respectively. Thirty-two out of 36 women who had a plasma sample obtained at, or just prior to, delivery had an undetectable viral load (< 50 to < 400 copies/mL). Adverse events that were definitely attributed to NVP included a generalized rash (n = 2) and hepatitis (n = 2). Obstetric complications occurred in nine women (19.5%), which was not statistically different (P = 0.36) from that found in a historical (1990-96) control group 7/51 (14%). The rate of preterm delivery (13%) was similar to that previously reported in HIV-1 infected pregnant women (18%). CONCLUSIONS: NVP (as part of highly active antiretroviral therapy) reduced plasma viraemia to below the limit of detection in 89% of women. It was generally well tolerated and clinical and laboratory adverse events were infrequent. There was no evidence of an increase in obstetric complications including preterm delivery during the second and third trimesters of pregnancy.

Adult↗

Selective media for the specific isolation and enumeration of Botrytis cinerea conidia.

AIMS: To develop selective media for the enumeration of Botrytis cinerea. METHODS AND RESULTS: Two new media, Botrytis Selective Medium (BSM) and Botrytis Spore Trap Medium (BSTM), were developed and compared with currently available media for the enumeration of B. cinerea conidia from the environment. The new Botrytis media proved advantageous over previous media because they were easier to prepare, had greater selectivity and allowed enumeration when a greater number of colony-forming units were present on individual plates. CONCLUSION: BSM and BSTM were shown to be suitable selective media for the enumeration of B. cinerea conidia from the environment. SIGNIFICANCE AND IMPACT OF THE STUDY: The media developed can be used to monitor the population of the pathogen B. cinerea and will allow detailed studies within the crop environments.

Ascomycota↗

Quantification of trichothecene-producing Fusarium species in harvested grain by competitive PCR to determine efficacies of fungicides against Fusarium head blight of winter wheat.

We developed a PCR-based assay to quantify trichothecene-producing Fusarium based on primers derived from the trichodiene synthase gene (Tri5). The primers were tested against a range of fusarium head blight (FHB) (also known as scab) pathogens and found to amplify specifically a 260-bp product from 25 isolates belonging to six trichothecene-producing Fusarium species. Amounts of the trichothecene-producing Fusarium and the trichothecene mycotoxin deoxynivalenol (DON) in harvested grain from a field trial designed to test the efficacies of the fungicides metconazole, azoxystrobin, and tebuconazole to control FHB were quantified. No correlation was found between FHB severity and DON in harvested grain, but a good correlation existed between the amount of trichothecene-producing Fusarium and DON present within grain. Azoxystrobin did not affect levels of trichothecene-producing Fusarium compared with those of untreated controls. Metconazole and tebuconazole significantly reduced the amount of trichothecene-producing Fusarium in harvested grain. We hypothesize that the fungicides affected the relationship between FHB severity and the amount of DON in harvested grain by altering the proportion of trichothecene-producing Fusarium within the FHB disease complex and not by altering the rate of DON production. The Tri5 quantitative PCR assay will aid research directed towards reducing amounts of trichothecene mycotoxins in food and animal feed.

Antifungal Agents↗