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Biomedical subjects

S Barton

Publications and source records attributed to S Barton.

At least 19 recordsLinked to original sources

Auditory verbal hallucinations and dysfunction of the neural substrates of speech.

OBJECTIVE: to evaluate the neural substrate of auditory verbal hallucinations (AVH), the correlation between AVH and subvocal speech (hereafter SVS), and the relationship between speech and AVH. METHOD: we reviewed the papers found by an electronic literature search on hallucinations and speech. The review was extended to the papers cited in these publications and to classical works. RESULTS: there is no conclusive evidence of structural abnormality of the speech perception area in hallucinating schizophrenic patients. However there is evidence of electrophysiological abnormalities of the auditory and speech perception cortices. Functional imaging data are inconsistent, yet point to the left superior temporal gyrus as one of the neural substrates for AVH. There is also evidence that SVS could accompany the experience of AVH. CONCLUSION: there is evidence that dysfunction of brain areas responsible for speech generation is a fundamental mechanism for generating AVH in schizophrenia. It results in a secondary activation of Wernicke's area (speech perception) and Broca's area (speech expression). The first leading to the experience of hallucinations, and the second, eventually, gives rise to a variable degree of vocal muscle activity detectable by EMG, and/or faint vocalizations detectable by sensitive microphones placed at proximity of the larynx. Direct stimulation or disease of Wernicke's area produces AVH without SVS.

Brain↗

Biomechanical evaluation of the origin of the long head of the biceps tendon.

PURPOSE: Lesions of the superior glenoid labrum extending anterior and posterior (SLAP) have recently been recognized as important sources of shoulder pain and dysfunction. Among the 4 described types of SLAP lesions, the type II SLAP involves detachment of the superior labrum from the bony glenoid and destabilization of the origin of the long head of the biceps tendon (LHBT). The purpose of this cadaveric biomechanical study was to evaluate the relative contribution regarding linear stiffness and displacement under load of the 2 origins of the LHBT: the superior glenoid labrum and the supraglenoid tubercle (the biceps anchor). TYPE OF STUDY: Cadaveric biomechanical study. METHODS: Seven pairs of fresh-frozen cadaveric shoulders were dissected free of all soft tissue except for the glenoid labrum and LHBT. Tension from 0 to 55 N was applied to the LHBT while keeping the tendon perpendicular to the face of the glenoid. Each specimen was tested for linear stiffness and biceps tendon displacement in the intact state, after releasing 1 of the LHBT origins, and after releasing the remaining origin. RESULTS: The average stiffness of the LHBT origin was 103 N/mm. Sectioning the anchor alone resulted in a 52% reduction in linear stiffness, whereas only detaching the superior glenoid labrum from the 10 o'clock to the 2 o'clock position resulted in a 15% reduction in linear stiffness. Maximum displacement of the biceps tendon origin in the intact state at the 55 N load averaged 0.99 mm. With a minimum load applied, displacement changed less than 1 mm unless both origins were released. CONCLUSIONS: The results indicate that the biceps anchor is the primary restraint of the LHBT and that the superior labrum is a secondary restraint in regard to linear stiffness. However, disruption of both restraints is required to produce the laxity typically seen in a type II SLAP lesion.

Adult↗

Why do GPs not implement evidence-based guidelines? A descriptive study.

BACKGROUND: There is an acknowledged gap between research findings and their implementation in clinical practice despite the existence of effective educational interventions. OBJECTIVES: Our aim was to identify what is impeding GPs from pursuing currently recognized good practice and implementing evidence-based guidelines in their management of hypertension in the elderly. METHOD: We carried out a qualitative study using semi-structured interviews conducted during focus group outreach visits to 34 GPs from nine practices in Merseyside involved in an educational programme designed to improve the management of hypertension in the elderly. RESULTS: Several barriers to the implementation of evidence-based guidelines in the management of hypertension in the elderly were identified. These included: doubts about the applicability of trial data to particular patients; the poor adherence of GPs to practice protocols; ageist attitudes of some GPs; the effect of time pressure and financial considerations making the subject a low priority; the absence of an effective computer system; and the absence of an educational mentor. All participants demonstrated a very positive attitude to practice-based education. They also welcomed external audit data, which compared their performance with that of other practices. Single-handed GPs were particularly enthusiastic about this approach as it provided them with the peer pressure they lacked. CONCLUSIONS: In order to bridge the gap between research and practice, educators need to address the various 'barriers to change' amongst practitioners.

Evidence-Based Medicine↗

An evaluation of near patient tests for detecting herpes simplex virus type-2 antibody.

OBJECTIVES: To examine the "in use" test characteristics of the POCkit "near patient" HSV-2 rapid test for the detection of HSV-2 IgG antibodies for use in the clinic. This test relies on a visual interpretation of the result. METHODS: 2093 serum samples, 229 from UK and 919 from Italian genitourinary medicine clinic patients and 945 from obstetric and gynaecology clinic patients in Italy were tested. Tests were carried out according to manufacturers' protocol in the United Kingdom and Italy. Three readers independently recorded a score for each test carried out and the results were compared. RESULTS: In the UK study, the three readers disagreed on the result on 5.2% of tests. In the Italian study, there was disagreement in 10.2% of tests. CONCLUSIONS: This study has demonstrated a problem in the subjective nature of the interpretation of the POCkit HSV-2 test. It highlights the need for adequate training of clinic staff and the need for clinics to adopt policies of quality assurance and ongoing monitoring which will ensure the validity and accuracy of this clinic based test.

Antibodies, Viral↗

Virological failure among patients on HAART from across Europe: results from the EuroSIDA study.

OBJECTIVES: To monitor the response to highly active antiretroviral therapy (HAART) over time and the proportions of patients with poor virological control in order to help provide some insight into drug resistance. DESIGN: Analysis of data from the EuroSIDA study; an observational study initiated in 1994 of almost 8500 patients with HIV from across Europe. METHODS: Patients who initiated HAART, and had both a CD4 lymphocyte count and viral load measured in the 3 months prior to starting HAART, were included in analyses. The proportion of patients with a poor virological response (defined as a viral load of > 10,000 copies/ml, using either a single measure or two consecutive measures) at 16 and 48 weeks was determined. Multivariate logistical regression was used to determine the factors associated with a poor virological response at both time points. RESULTS: Median CD4 cell count at starting HAART was 218 cells/mm3 [interquartile range (IQR), 113-327 cells/mm3] and median viral load was 4.36 log10 copies/ml (IQR, 3.57-5.04 log10 copies/ml). At 16 weeks, 16% had a viral load of > 10,000 copies/ml based on a single viral load measure and 10% if the more stringent definition of two consecutive viral loads above this level was used. At 48 weeks these proportions were 19% and 13%, respectively. Compared with patients from Southern Europe, patients from both Central and Northern Europe had approximately half the chance of a poor virological response at 16 weeks (odds ratios 0.53 and 0.47, P = 0.0015 and P < 0.0001, respectively), while at 48 weeks both regions still had approximately a 25% reduced chance of a poor virological response, but this was no longer statistically significant (odds ratio 0.77 and 0.75, P = 0.17 and P = 0.13, respectively). CONCLUSIONS: There were marked difference in virological response to HAART across regions of Europe, which may be partly explained by regional differences in access to HAART and utilisation. If drug resistance is closely related to virological failure, these results may help to provide an early insight into the potential problem of drug resistance across Europe. Continued follow-up is essential to monitor patients with poor virological control.

Anti-HIV Agents↗

Evaluation of sperm washing as a potential method of reducing HIV transmission in HIV-discordant couples wishing to have children.

OBJECTIVE: A number of discordant couples, in whom the man is HIV positive and the woman is HIV negative, wish to have children. To conceive they must abandon protected sex, posing a risk of HIV transmission to the woman and so to the child. In such circumstances purification of spermatozoa ('sperm-washing') to inseminate the woman artificially has been proposed as a method of reducing the risk of transmission. Here we evaluate whether this does represent a true risk reduction. METHODS: Semen samples from HIV-positive patients were separated into spermatozoa, non-sperm cells (NSCs) and plasma fractions. The amount of viral RNA present in each fraction was measured and compared with the level in the peripheral blood. Each fraction was also assessed for the presence of proviral DNA. The ability of spermatozoa to be infected was assessed by evaluating for the presence of HIV receptors, i.e. CD4, CCR5 and CXCR4 on the surface of the sperm, by flow cytometry. RESULTS: A poor correlation was found between the levels of HIV in blood and semen. Within the semen the virus was restricted to the plasma and/or NSCs. All spermatozoa were negative for viral RNA or proviral DNA. Spermatozoa did not express significant levels of CD4, CCR5 or CXCR4, suggesting that they are unlikely to be major targets for HIV infection. CONCLUSIONS: These data suggest that spermatozoa are not major targets of HIV infection. Purifying spermatozoa reduced the level of HIV RNA and proviral DNA to below the detection limit of the assays irrespective of the amount of virus present in the unfractionated semen. On the basis of these data we would recommend 'sperm-washing' followed by insemination as a safer alternative to natural conception for HIV-discordant couples wishing to have children.

DNA, Viral↗

Therapeutic substitution and therapeutic conservatism as cost-containment strategies in primary care: a study of fundholders and non-fundholders.

BACKGROUND: General practice (GP) fundholders contained prescribing costs by restricting the rise in volume of prescribing and by increasing generic prescribing. It is uncertain whether they used more sophisticated approaches to medicine choice in attempts to contain costs. AIM: To examine whether fundholding practices have adopted medicine-specific strategies to contain prescribing costs--i.e. switching to less expensive but equally effective medicines or resisting the uptake of newer more expensive medicines--by examination of the prescribing of ulcer-healing and antidepressant medicines in the period before and after practices became fundholders. METHOD: Comparison of prescribing data of 52 fundholding practices before fundholding and after fundholding with that of matched non-fundholding practices. Measures examined were prescribing costs (net ingredient cost in each therapeutic area per ASTRO-pu); prescribing volume (defined daily doses per ASTRO-pu); the proportion of all ulcer-healing medicines prescribed as cimetidine, ranitidine, nizatidine, and as proton pump inhibitors; and the proportion of all antidepressant medicines prescribed as selective serotonin re-uptake inhibitors. RESULTS: In comparison with non-fundholding practices, fundholders increasingly prescribed less expensive medicines (cimetidine and nizatidine) within the class of histamine2 receptor antagonists. However, fundholders adopted proton pump inhibitors or selective serotonin re-uptake inhibitors at the same rate as non-fundholders. CONCLUSION: Fundholders have used therapeutic substitution with medicines of equal effectiveness to contain prescribing costs. There is no evidence that fundholders have been slower than non-fundholders to use newer, more expensive medicines.

Aged↗

Addressing barriers to change: an RCT of practice-based education to improve the management of hypertension in the elderly.

BACKGROUND: In the future, primary care groups (PCGs) will have to consider how best to apply audit and education to fulfil their commitment to clinical governance and to facilitate the implementation of research findings. AIM: To establish whether an exploration of 'barriers to change' can enhance the effectiveness of an educational intervention designed to improve the management of hypertension in the elderly. METHOD: A parallel-arm, randomized, single-blind, controlled trial of practice-based educational visits in 18 practices. These practices had previously taken part in a multipractice audit of the management of hypertension in the elderly. Both groups received outreach visits in their own practice, during which they received the results of the previous audit. The nine 'intervention' practices were encouraged to explore barriers that would prevent them from implementing pertinent research findings. The control group was not encouraged to do this. The main outcome measure of the trial was determined in advance as 'the stated management of systolic hypertension in patients aged 70 to 79'. A secondary endpoint was the stated management of a specific patient scenario. The endpoints were tested by questionnaire before and after the educational intervention. RESULTS: For the primary endpoint, there was a statistically significant difference in the stated threshold for treating systolic hypertension between intervention and control groups after the visits (161.8 mmHg versus 167.2 mmHg; P = 0.007). For the secondary endpoint, there was also a statistically significant difference between the two groups, after the visits, in their willingness to treat a 70-year-old male with mild hypertension (89% of doctors would treat in the intervention group versus 57% in the control group; P = 0.047). CONCLUSION: The effectiveness of an educational intervention is significantly improved by addressing the barriers preventing practitioners from implementing the findings of research.

Aged↗

A study of imidazole-based nuclear magnetic resonance probes of cellular pH.

A number of imidazole-based compounds were tested for their utility as (1)H NMR molecular probes of intracellular pH. Imidazole, previously found useful as a probe of erythrocyte pH, reported a pH in perfused canine glioma cells that was more than 1 pH unit lower than that reported by inorganic phosphate, consistent with the known lysosomal compartmentation of the molecule. Imidazole acetate, also proposed as an NMR probe of cellular pH, was found not to enter the cells of this study. Histidine was found to be readily taken up by cells and reported a pH consistent with that reported by inorganic phosphate. Using the chemical shift of the histidine H2 proton in cells incubated with 10 mM histidine, cellular pH measurements could be obtained in less than 1 s. This compares quite favorably with the measurement time, typically several minutes, needed to assess in vivo pH by (31)P NMR. The use of histidine as a probe of pH is demonstrated in perfused canine and rat glioma cells subjected to ischemia or to low extracellular pH.

Animals↗

Survival in 2367 zidovudine-treated patients according to use of other nucleoside analogue drugs. The EuroSIDA Study Group.

To evaluate survival according to use of different nucleoside drugs in a routine clinical setting, we studied a large group of zidovudine-treated patients seen in clinics across Europe. A total of 3128 subjects was recruited to the observational, prospective EuroSIDA study in May 1994. These were consecutive patients (up to a predefined limit) seen at outpatient clinics in 37 centers from 16 European countries and followed at 6-month intervals by use of standardized forms completed by clinicians at the respective centers. This report concerns 2367 subjects who began antiretroviral therapy with a regime that included zidovudine either before study entry or during the course of follow-up. Cox proportional hazards models were fitted, with use of other antiretroviral drugs, CD4 count, and date of development of AIDS fitted as time-dependent covariates. Survival times from start of therapy were left truncated at study entry to avoid survival bias. In addition to zidovudine, antiretroviral drugs used included didanosine (ddI) (n = 1119; median 1.6 years after starting zidovudine), dideoxycytidine (ddC) (n = 592; median 1.9 years after starting zidovudine), stavudine (d4T) (n = 241; median 2.9 years after starting zidovudine) and lamivudine (3TC) (n = 33 ; median 2.7 years after starting zidovudine). Of the 2367 patients, 613 died during follow-up. Overall, risk of death was reduced in those zidovudine-treated patients who began at least one other nucleoside analogue drug with or after taking zidovudine (relative hazard [RH], 0.61; 95% confidence interval [CI], 0.51-0.72, adjusting for CD4 count, development of AIDS, and age). Fitting each drug separately, there was a larger association with reduced mortality for starting 3TC (RH, 0.41; 95% CI, 0.28-0.62) than for starting ddl (RH, 0.79; 95% CI, 0.67-0.93), ddC (RH, 0.74; 95% CI, 0.59-0.92) or d4T (RH, 0.67; 95% CI, 0.49-0.91). These results suggest that the beneficial effect of nucleoside combination therapy identified in controlled trials can be seen in routine clinical practice.

Adult↗

Sodium selenite and N-acetylcysteine in antiretroviral-naive HIV-1-infected patients: a randomized, controlled pilot study.

BACKGROUND: The aim of this work was to study the effects of combined oral administration of N-acetylcysteine (NAC) and sodium selenite (Se) on plasma glutathione (GSH), lymphocyte subpopulations and viral load in asymptomatic human immunodeficiency virus (HIV)-infected patients. METHODS: We used a prospective, randomized and controlled therapy trial with partial crossover. Twenty-four antiretroviral-naive HIV-infected outpatients at Centers for Disease Control (CDC)'93 stages I and II were randomized to receive the antioxidant combination NAC 600 mg t.i.d. and Se 500 micrograms per day for either 24 weeks (group A, n = 13) or from the end of week 12 (group B, n = 11) until the end of week 24. Thus, group B served as untreated control during the first 12 weeks. RESULTS: There was (a) a trend towards an increase in the percentage of CD4+ lymphocytes after 6 weeks (P = 0.08); (b) an increase in the CD4/CD8 ratio after 6 and 12 weeks (P = 0.02 and P = 0.04 respectively); and (c) a decrease in the absolute CD8/CD38 count and percentage of lymphocytes after 6 weeks (P = 0.002 and P = 0.033 respectively) and 12 weeks (P = 0.033, P = 0.1 respectively) in group A compared with the control period of group B. The effects observed in group A were, however, not paralleled to the same extent by group B after crossing-over to treatment after 12 weeks. In addition, erythrocyte glutathione peroxidase (GSH-Px) activity and GSH, glutathionedisulphide (GSSG) concentrations and the reduced/total GSH ratio were not affected by the treatment. Serum selenium levels increased significantly (P < 0.001) upon treatment. Viral load was not altered. CONCLUSIONS: The changes in lymphocyte subsets after NAC/Se treatment were not comparable to those after standard antiretroviral drug therapy. This, however, does not preclude per se possible benefits of antioxidant supplementation in HIV disease.

Acetylcysteine↗

Health promotion in different medical settings: women's health, community health and private practice.

This paper describes the health promotion role of doctors in two medical practice settings: women's and community health centres, and fee-for-service practice. It proposes the establishment of divisions of primary health care in Australia which would be multi-disciplinary and focus on community-wide health issues. The paper is based on data from an interview survey of medical practitioners who had worked in metropolitan Adelaide women's and community health centres and from a questionnaire survey of GPs in private practice. The types of health promotion activity by the doctors in the different settings are discussed. It is concluded that private practice GPs are involved primarily in providing health education advice to individual patients. Doctors within women's and community health centres are more likely to report involvement in group health promotion activity and broader community development initiatives. The study concludes that health promotion which focuses on the health of the local community is best conducted within multidisciplinary health centres. GPs in private practice are limited by the structure of their setting (particularly the fee-for-service basis and reliance on a single discipline) to health promotion which focuses on the needs of individual patients.

Attitude of Health Personnel↗