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Biomedical subjects

J Anderson

Publications and source records attributed to J Anderson.

At least 37 records · Page 2Linked to original sources

Differentiating infection from vaccination in foot-and-mouth-disease: evaluation of an ELISA based on recombinant 3ABC.

Recent devastating outbreaks of foot-and-mouth disease (FMD) in Europe have reopened the discussion about the adequacy of the non-vaccination strategy implemented by the EU in 1991. Here we describe the evaluation of a new commercially available test kit for the discrimination between vaccination and infection. The test is based on the detection of antibodies against the recombinant non-structural (NS) protein 3ABC. In contrast to immunization with vaccines free of 3ABC, these antibodies are elicited as a consequence of infection. Testing more than 3600 negative sera from several countries revealed a specificity of > 99% for bovine, ovine, and porcine samples. Antibodies specific for 3ABC can be detected as soon as 10 days post-infection. As compared with the occurrence of antibodies against structural proteins of FMDV, anti-3ABC antibodies can be detected 5-10 days later, depending on the species. No anti-3ABC antibodies were detected in sera from vaccination experiments or in field sera from vaccinated animals. However, anti-3ABC antibodies can be detected in vaccinated animals upon challenge. These results provide evidence that this test can facilitate the use of vaccines in new strategies against FMD.

Animals↗

Outcome of patients with HIV-related germ cell tumours: a case-control study.

Testicular germ cell tumour (GCT) is not an AIDS-defining illness despite an increased incidence in men with HIV infection. We performed a matched case-control study comparing outcomes in HIV-positive men and the general population with GCT, using three age and stage matched controls for each case. There was no difference in the 5-year GCT-free survival between cases and controls. However, overall survival was significantly decreased in the cases (log rank P=0.03). HIV was responsible for 70% of this mortality. The relapse-free survival for stage I patients treated with orchidectomy and surveillance was not affected by HIV status (log rank P=0.68). There was no difference in disease free survival in patients with metastatic disease (log rank P=0.78). The overall survival has not improved since the introduction of highly active antiretroviral therapy (log rank P=0.4). Thus, HIV-related GCT is not more aggressive than GCT in the general population.

Adult↗

Validation of a foot-and-mouth disease antibody screening solid-phase competition ELISA (SPCE).

This paper describes the validation of a solid-phase competition enzyme-linked immunosorbent assay (SPCE) for the serological detection of antibody to serotype O foot-and-mouth disease (FMD) in sheep, cattle and pigs. The specificity of the SPCE was calculated from the results of testing known negative sera from sheep, cattle and pigs (n=3030, 1418 and 1495, respectively). The mean percentage inhibition (PI) for known negative sheep, cattle and pig sera were 19.3, 24.1 and 20.8%, respectively. The specificity of the SPCE at a cut-off point (COP) of 60 PI was 99.50% for sheep sera, 99.44% for cattle sera and 100% for pig sera. The analytical sensitivity of the SPCE was examined by testing sera from sheep, cattle and pigs. Based on the testing of serial bleeds from experimentally infected animals, seroconversion at the 60 PI COP occurred between 4 and 9 days post-infection or -exposure, similar to that observed using the virus neutralisation test (VNT) with a COP of 1/45. When applied to 267 sheep and 143 pig samples, that were obtained in Great Britain (GB) during the 2001 FMD UK outbreak, the SPCE identified more positive samples than did the VNT. Estimates of the accuracy, repeatability and reproducibility of the SPCE were verified during the large-scale serosurveillance necessitated by the 2001 outbreak. Results from field and experimental sera showed that when compared against the VNT, the sensitivity of the SPCE was less affected by the choice of virus strain used in the test. Using the O(1) UKG 2001 FMD virus in the VNT with samples representative of the uninfected GB sheep population, the test specificity was 100% at a COP of 1/45.

Animals↗

Women from Africa living with HIV in London: a descriptive study.

There are no studies that have examined the particular needs and experiences of African women living with HIV in the UK at a time when they represent an increasingly large proportion of the UK HIV epidemic. This study explores the illness biographies and daily lives of HIV-positive African women receiving treatment in London. Sixty-two women from 11 African countries attending HIV specialist clinics in five London hospitals participated in self-completion questionnaires and in depth semi-structured interviews. Using a narrative approach, women were asked to talk about their HIV status in the broader context of their life history. Important differences exist within this group based mainly on nationality, income, education level and legal status in the UK. However, marked similarities also emerged which were related in part to their situation as migrants and were compounded by their illness. Stigma, both actual and perceived, had a profound impact on women's lives, making control of information about their situation a matter of acute concern. This had an effect on how women accessed health services and voluntary sector agencies. The resilience of women in dealing with difficulties in their lives was strengthened by religious belief. Such similarities and differences need to be properly understood by health and social care professionals if they are to offer the most appropriate care for this growing population of patients.

Adult↗

Portfolios for assessment of paediatric specialist registrars.

INTRODUCTION: In 1997 the Royal College of Paediatrics and Child Health introduced portfolios to guide and monitor the learning of specialist registrars. We studied their value for assessment. METHODS: Using Bigg's SOLO criteria we devised a marking scheme based on 6 domains of competence: clinical, communication, teaching and learning, ethics and attitudes, management and evaluation, and creation of evidence. We rated portfolios according to quality of evidence presented and expectations by year of training. We similarly assessed trainee performance in the annual record of in-training assessment (RITA) interview. Specific advice based on the results of the first portfolio assessments was circulated to all trainees, instructing them to increase the structure and decrease the bulk of portfolios. A second sample of portfolios was reviewed a year later, using similar evaluations, to determine the effects. RESULTS: A total of 76 portfolios were assessed in year 1 by a single rater; 30 portfolios were assessed in year 2 by 2 independent raters. The quality of documentation improved from year 1 to year 2 but there was no significant increase in portfolio scores. The inter-rater correlation coefficient of the portfolio assessment method was 0.52 (Cohen's kappa 0.35). The inter-rater correlation coefficient of the RITA interview was 0.71 (Cohen's kappa 0.38). There was moderate inter-assessment correlation between portfolios and RITA interviews (kappa 0.26 in year 1 and 0.29 in year 2). Generalisability analysis suggested that 5 successive ratings by a single observer or independent ratings by 4 observers on the same occasion would be needed to yield a generalisability coefficient > 0.8 for overall portfolio rating. CONCLUSIONS: This method of portfolio assessment is insufficiently reliable as a sole method for high stakes, single-instance assessment, but has a place as part of a triangulation process. Repeated portfolio assessment by paired observers would increase reliability. Longer term studies are required to establish whether portfolio assessment positively influences learner behaviour.

Clinical Competence↗

Comparison of two 3ABC enzyme-linked immunosorbent assays for diagnosis of multiple-serotype foot-and-mouth disease in a cattle population in an area of endemicity.

The development of a serological test for foot-and-mouth disease virus (FMDV) which is quick and easy to use, which can identify all seven serotypes, and which can differentiate vaccinated from convalescing or potential virus carriers would be a major advance in the epidemiological toolkit for FMDV. The nonstructural polyprotein 3ABC has recently been proposed as such an antigen, and a number of diagnostic tests are being developed. This paper evaluates the performance of two FMDV tests for antibodies to nonstructural proteins in an unvaccinated cattle population from a region of Cameroon with endemic multiple-serotype FMD. The CHEKIT-FMD-3ABC bo-ov (CHEKIT) enzyme-linked immunosorbent assay (ELISA) (Bommeli Diagnostics/Intervet) is a commercially available test that was compared with a competitive 3ABC ELISA (C-ELISA) developed in Denmark. The tests were compared with the virus neutralization test as the "gold standard." Diagnostic sensitivity and specificity were examined over a range of test cutoffs by using receiver operating characteristic curves, which allowed comparison of the overall performance of each test. The results indicated that the CHEKIT ELISA kit was 23% sensitive and 98% specific and the Danish C-ELISA was 71% sensitive and 90% specific at the recommended cutoff. These results have important implications if the tests are to be used to screen herds or individual cattle in surveillance programs, at border crossings for import-export clearance, or following emergency vaccination in an outbreak situation.

Animals↗

Iatrogenic illness on a general medical service at a university hospital. 1981.

We found that 36% of 815 consecutive patients on a general medical service of a university hospital had an iatrogenic illness. In 9% of all persons admitted, the incident was considered major in that it threatened life or produced considerable disability. In 2% of the 815 patients, the iatrogenic illness was believed to contribute to the death of the patient. Exposure to drugs was a particularly important factor in determining which patients had complications. Given the increasing number and complexity of diagnostic procedures and therapeutic agents, monitoring of untoward events is essential, and attention should be paid to educational efforts to reduce the risks of iatrogenic illness.

Adult↗

Making a vaccinate-to-live policy a reality in foot-and-mouth disease.

Public opinion and the availability of new technologies are making the use of 'stamping- out' an increasingly unattractive option as the method of first choice for foot-and-mouth disease (FMD) control in FMD-free countries or zones seeking to control incursion of disease. There is therefore increasing pressure to adopt a 'vaccinate-to-live' policy in these circumstances. For a successful vaccinate-to-live policy, veterinary services need access to appropriate, licensed vaccines; to have adequate contingency plans to ensure that they can deliver the required vaccine, where and when it is needed; and to have developed an 'exit strategy' that enables recognition of freedom from disease as quickly as possible. This paper discusses progress towards these requirements and the problems that still need to be addressed before a vaccinate-to-live policy can become the option of first resort.

Animals↗

Learning on the Web. Case 7: recurrent pleural effusions, resistant atrial arrhythmias, and abnormal liver function tests: general medicine or cardiology?

A 65 year old man presented with recurrent pleural effusions. Repeated pleural fluid examination and pleural biopsy were unremarkable. Pericardial calcification was noted on admission and attributed to an uncomplicated episode of pericarditis 30 years previously. His symptoms and signs were not thought not to be associated with the heart. While awaiting an open pleural biopsy the patient was admitted with a further pleural effusion, jaundice, resistant atrial arrhythmias, and dyspnoea. Hepatic investigations including autoantibody screen and transjugular liver biopsy were normal. The significance of these signs and symptoms, the diagnosis, and the management of these problems are discussed in an interactive case presentation.

Aged↗

Basiliximab (anti-CD25) in combination with steroids may be an effective new treatment for steroid-resistant ulcerative colitis.

BACKGROUND: Steroid resistance represents a major clinical problem in the treatment of ulcerative colitis. In vitro, interleukin-2 renders lymphocytes steroid resistant. AIM: To explore the therapeutic potential of interleukin-2 receptor blockade in steroid-resistant ulcerative colitis with both in vitro measures and a pilot in vivo study. METHODS: Ten patients with steroid-resistant ulcerative colitis received a single bolus of 40 mg of intravenous basiliximab plus steroid treatment in an open-label, uncontrolled, 24-week study. The outcome was assessed using the Ulcerative Colitis Symptom Score, rectal biopsy and Inflammatory Bowel Disease Questionnaire. Lymphocyte steroid sensitivity was measured in vitro in 39 subjects in the presence or absence of basiliximab. RESULTS: Nine of the 10 patients achieved clinical remission within 8 weeks. At 24 weeks, seven patients were in clinical remission. Marked improvement in the Ulcerative Colitis Symptom Score was seen by 1 week (P = 0.004) and on rectal biopsy and Inflammatory Bowel Disease Questionnaire by 2 weeks (both P < 0.05). Improvements persisted to 24 weeks (Ulcerative Colitis Symptom Score, Inflammatory Bowel Disease Questionnaire, both P < 0.005). Eight of the nine responders relapsed (median, 9 weeks), but remission was re-achieved with further corticosteroids and the addition of azathioprine. At 24 weeks, seven patients were in full clinical remission, five off all steroid therapy. In vitro measurement of lymphocyte steroid sensitivity demonstrated steroid resistance in 22% of subjects. All were rendered steroid sensitive in the presence of basiliximab. CONCLUSIONS: Basiliximab appears to be effective at inducing remission in steroid-resistant ulcerative colitis. In vitro, basiliximab also produced a dramatic increase in lymphocyte steroid sensitivity in healthy subjects. Confirmation in randomized controlled studies is required.

Adult↗

Macrophage proteomic fingerprinting predicts HIV-1-associated cognitive impairment.

BACKGROUND: Specific proteins produced from monocytes may be linked to the pathogenesis and aid in the diagnosis of HIV-1-associated dementia (HAD). OBJECTIVE: The authors assessed whether a diagnostic phenomic protein profile could be obtained from monocyte-derived macrophages (MDM) from HIV-1-infected patients with cognitive impairment. METHODS: Twenty-one HIV-1-infected Hispanic women and 10 seronegative controls matched by age and sex were followed at the University of Puerto Rico Medical Sciences Campus, where neuropsychological, immune, and viral parameters were tested. Monocytes were recovered by Percoll gradient centrifugation from peripheral blood mononuclear cells. MDM lysates were prepared after 7 days of cultivation and protein profiles analyzed by surface enhanced laser desorption/ionization (SELDI)-time of flight (TOF) ProteinChip tests. Classification trees were prepared for statistical analyses. RESULTS: A total of 177 protein peaks from 2 to 80 kDa were evaluated in 31 patient MDM lysates by SELDI-TOF ProteinChip assays. Select protein peaks, at 5028 and 4320 Da, separated HIV-1-infected from HIV-1-seronegative subjects with a sensitivity of 100% and a specificity of 80%. Thirty-eight peaks were used to differentiate HIV-1-infected subjects with and without cognitive impairment. A 4348 Da protein separated the two groups with a sensitivity of 100% and a specificity of 75%. CONCLUSIONS: The identification of unique phenomic MDM profiles from cognitively impaired HIV-1-infected patients supports the hypothesis that changes in monocyte function parallel the development of HAD.

AIDS Dementia Complex↗

Multicenter study of human immunodeficiency virus-related germ cell tumors.

PURPOSE: Testicular germ cell tumors (GCT) occur at increased frequency in men with human immunodeficiency virus (HIV). This multicenter study addresses the characteristics of these tumors. PATIENTS AND METHODS: Patients with HIV-related GCT were identified from six HIV treatment centers. The incidence was calculated from the center with the most complete linked oncology and HIV databases. RESULTS: Thirty-five patients with HIV-related GCT were identified. The median age at GCT diagnosis was 34 years (range, 27 to 64 years). The median CD4 cell count was 315/mm3 (range, 90 to 960/mm3) at this time. The histologic classification was seminoma in 26 patients (74%) and nonseminomatous GCT in nine patients (26%). Twenty-one patients (60%) had stage I disease and 14 patients had metastatic disease. Overall six patients relapsed, three died from GCT, and seven died from HIV disease, resulting in a 2-year overall survival rate of 81%. HIV-related seminoma occurred more frequently than in the age- and sex-matched HIV-negative population, with a relative risk of 5.4 (95% confidence interval, 3.35 to 8.10); however, nonseminomatous GCT did not occur more frequently, and there was no change in the incidence of GCT since the introduction of highly active antiretroviral therapy. CONCLUSION: Testicular seminoma occurs significantly more frequently in HIV-positive men than in the matched control population. Patients with HIV-related GCTs present and should be treated in a similar manner to those in the HIV-negative population. After a median follow-up of 4.6 years, 9% of the patients died from GCT. Most of the mortality relates to HIV infection.

Adolescent↗

Role of metabotropic glutamate receptor subtype 5 (mGluR5) in the maintenance of cold hypersensitivity following a peripheral mononeuropathy in the rat.

The present series of experiments were designed to examine the contribution of metabotropic glutamate receptor subtype 5 (mGluR5) to neuropathic pain by determining the effects of the selective mGluR5 antagonist MPEP (2-methyl-6-(phenylethynyl)-pyridine) on neuropathy-induced cold hypersensitivity. Unilateral chronic constriction injury (CCI) to the sciatic nerve in rats produced an increase in the number of hind paw withdrawals from a cold surface (4 +/- 2 degrees C) which was dose-dependently inhibited by systemic (i.p.) injection of MPEP (ID(50) = 11.3 mg/kg). In vivo brain mGluR5 receptor occupancy following systemic (i.p.) MPEP revealed that >90% occupancy is required for behavioral efficacy. Intracerebroventricular (i.c.v.) injection of MPEP dose-dependently inhibited CCI-induced cold hypersensitivity (ID(50) = 123.5 nmol), while microinjection of MPEP directly into the rostral ventromedial medulla (RVM) potently inhibited this hypersensitivity (ID(50) = 1.3 pmol). A role for mGluR5 in the RVM was further supported by the observation that intra-RVM injection of the mGluR5 agonist CHPG (10 nmol; 2-chloro-5-hydroxyphenylglycine) produced cold hypersensitivity in naïve rats that was blocked by pretreatment with intra-RVM MPEP (3 nmol). Intrathecal (500 nmol; i.t.) or intraplantar (300 nmol; i.pl.) injection of MPEP was ineffective in reversing CCI-induced cold hypersensitivity. These results demonstrate that mGluR5 contributes to cold hypersensitivity following peripheral neuropathy exclusively at supraspinal sites in the CNS. Additionally, mGluR5 in the RVM significantly contributes to the maintenance of cold hypersensitivity, likely via activation of descending nociceptive facilitatory systems.

Animals↗

Early prostate cancer: prevention, treatment modalities, and quality of life issues.

Our understanding of the screening, prevention and treatment of early prostate cancer is improving. This is a result of new data from clinical trials and the incorporation of efficacy measures based on risk assessment and quality of life (QoL). This review aims to examine completed and ongoing clinical trials that address issues in early prostate cancer, including screening, prevention, treatment, and QoL. Prostate-specific antigen (PSA) testing has a crucial and evolving role in detecting primary prostate cancer, evaluating prevention interventions and assessing the effectiveness of treatment. Questions remain about the optimal PSA parameters appropriate for primary screening and for diagnosing relapse. Emerging and established data provide evidence that early intervention with hormone therapy, either as immediate or adjuvant therapy, delays progression in prostate cancer patients with intermediate or poor prognosis. The impact of therapeutic modality on QoL has become better characterized, as QoL instruments have been developed, validated and applied.

Aged↗

Epidemiology and prevention of unexpected in-hospital deaths.

INTRODUCTION: The medical literature has only documented the importace of adverse events in terms of patient outcomes and cost to the health service over the last decade. This review focuses on the incidence, risk factors and prevention on unexpected in-hospital deaths. DISCUSSION: The incidence of unexpected in-hospital deaths in the two major retrospective studies was 0.5% and 0.8% of all hospital admissions. A prospective study of surgical patients documented an incidence of nearly 7.1%. The risk factors that have been associated with hospital death include: increasing age; non-elective operative procedure; negligence; human error and unstable bedside observations in the hours prior to death. Although a number of intreventions have been suggested to prevent unexpected in-hospital deaths, very few studies have been performed to determine effectiveness. In a single institution historical control study, the introduction of a Medical Emergency Team was associated with 50% reduction in the casemix adjusted incidence of in-hospital cardiac arrest calls. CONCLUSION: There are a number of studies to suggest that in-hospital deaths are both predictable and preventable. More work is required to determine effective strategies to manage this problem.

Hospital Mortality↗

Nitrate levels and the age of groundwater from the Upper Devonian sandstone aquifer in Fife, Scotland.

The tritium concentrations in 13 groundwater samples from boreholes throughout the Upper Devonian sandstone aquifer of Fife have been measured. Due to atmospheric variations in tritium concentrations over the last century, this radioactive tracer can be used as a groundwater age indicator. In this study, the groundwater tritium concentrations have allowed for the area to be divided into three zones, and the variable chemistry of the groundwater samples, including the problem of recent elevated nitrate levels in the Fife Aquifer, has been interpreted in terms of their relative ages.

Environmental Monitoring↗