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Biomedical subjects

R Wood

Publications and source records attributed to R Wood.

At least 55 records · Page 3Linked to original sources

Forearm vasoreactivity in type 1diabetic subjects.

This study compared forearm vasoreactivity in 15 Type I diabetic subjects with 15 healthy controls. The groups were matched for age, exercise capacity, and the absence of other cardiovascular risk factors. Vasoreactivity was measured using strain gauge plethysmography, at rest, after arterial occlusion (OCC), and following OCC coupled with handgrip exercise (ROCC). Forearm blood flows were significantly elevated between conditions 2.58 +/- 0.37ml/100mltissue at rest to 26.80 +/- 6.56 after OCC and 32.80 +/- 8.26ml/100mltissue following ROCC in Type I diabetic subjects. There were no differences in forearm blood flow between groups for any of the conditions. These data indicate the degree of forearm blood flow is directly related to the intensity of the vasodilatory stimulus. However, our study did not reveal evidence of impaired vasodilatory capacity in Type I diabetic subjects compared to controls in the absence of other risk factors.

Adult↗

Extended scope of nursing practice: a multicentre randomised controlled trial of appropriately trained nurses and pre-registration house officers in pre-operative assessment in elective general surgery.

OBJECTIVES: (1) To determine whether pre-operative assessment carried out by an appropriately trained nurse (ATN) is equivalent in quality to that carried out by a pre-registration house officer (PRHO). (2) To assess whether pre-assessments carried out by ATNs and PRHOs are equivalent in terms of cost. (3) To determine whether assessments carried out by ATNs are acceptable to patients. (4) To investigate the quality of communication between senior medical staff and ATNs. DESIGN: The study design was principally a prospective randomised equivalence trial but was accompanied by additional qualitative assessment of patient and staff perceptions, and an economic evaluation. SETTING: The study was carried out at four NHS hospitals, three of which were teaching hospitals, in three NHS Trusts in Southampton, Sheffield and Doncaster. SUBJECTS: All patients attending at one site for assessment prior to general anaesthetic for elective general, vascular, urological or breast surgery were potentially included in the study. Of 1907 patients who were randomised, 1874 completed the study with a full evaluation. INTERVENTIONS: The intervention consisted of a pre-operative assessment carried out by either an ATN or a PRHO. Of the patients who completed the study with a full evaluation, 926 patients were randomised to the PRHO arm of the trial and 948 to the ATN arm. Three ATNs took part in the study, one from each centre, together with a total of 87 PRHOs. MAIN OUTCOME MEASURES: Immediately following the initial assessment of a patient by a PRHO or an ATN, one of a number of clinical research fellows, all specialist registrars in anaesthetics, repeated the assessment and recorded it on a study form, together with a list of investigations required. The clinical research fellow then evaluated the competency of the initial assessor by comparing the quality of their assessment with their own. Any deficiencies in ordering of investigations and referral to other specialities were met in order to maximise patient care. Three areas of ATN and PRHO performance were judged separately, history taking, examination and ordering of tests, and each was graded into one of four categories, the most important of which was under-assessment, which would possibly have affected peri-operative management. In the case of ordering of tests, it was possible to have both over- and under-assessed a patient on different tests. RESULTS: The pre-operative assessments carried out by the ATNs were essentially equivalent to those performed by the PRHOs in terms of under-assessment that might possibly have affected peri-operative management, although there was variation between the ATNs in terms of the quality of history taking. This may be related to the low number of patients seen at one study site. PRHOs ordered significantly more unnecessary tests than the ATNs. The substitution of ATNs for PRHOs was calculated to be cost neutral. The results of the qualitative assessment showed that the use of ATNs for pre-operative assessment was acceptable to patients; however, there was no evidence that communication between senior medical staff and those carrying out pre-operative assessments was improved by their introduction. CONCLUSIONS: This study demonstrated no reason to inhibit the development of fully nurse-led pre-operative assessment, provided that the nurses are appropriately trained and maintain sufficient workload to retain skills. CONCLUSIONS--IMPLICATIONS FOR THE HEALTH SERVICE: ATNs provide an acceptable and efficient alternative to PRHOs for the purposes of routine pre-operative assessment. Consideration will have to be given, however, to the positions of these nurses within the surgical team, and also to their career structure. CONCLUSIONS--RECOMMENDATIONS FOR FUTURE RESEARCH: Further research is needed in the following areas: (1) the extent and type of training needed for nurses undertaking the pre-operative assessment role; (2) the use, costs and benefits of routine pre-operative testing.

Clinical Competence↗

Association between tuberculosis and HIV disease progression in a high tuberculosis prevalence area.

SETTING: Adult human immunodeficiency virus (HIV) clinics affiliated to the University of Cape Town, South Africa. OBJECTIVE: To assess the impact of tuberculosis on HIV-1 disease progression in an area with high tuberculosis prevalence and minimal antiretroviral therapy use. DESIGN: Prospective patient cohort study. METHODS: Age, race, risk status, CD4+ T-lymphocyte count, history of AIDS, prophylactic co-trimoxazole and antiretroviral therapy were controlled for in a time-dependent Cox proportional hazards regression model. RESULTS: Tuberculosis fulfilling the case definition developed in 158/609 patients in the 5-year observation period. Tuberculosis was associated with an increased risk of AIDS (adjusted risk ratio [RR] = 1.60, 95% confidence interval [CI] 1.08-2.41; P = 0.02) and death (adjusted RR = 2.16, 95% CI 1.29-3.59; P = 0.003). In a stratified analysis, the increased mortality associated with tuberculosis was observed only in patients with CD4+ T-lymphocyte count > 200 cells/microliter and in those without AIDS at baseline. CONCLUSION: The onset of tuberculosis in HIV-infected patients is associated with an increased risk of AIDS and death. Although a causal link cannot be established in an observational study, our findings support the view that prolonged immune activation induced by tuberculosis leads to prolonged increased HIV replication and consequent accelerated disease progression.

AIDS-Related Opportunistic Infections↗

AIDS in Africa--survival according to AIDS-defining illness.

OBJECTIVE: Evaluation of prognostic significance of the type of AIDS-defining illness (ADI) and performance status in a cohort of AIDS patients. DESIGN, SETTING, SUBJECTS, OUTCOME MEASURES: A retrospective analysis of 280 patients with AIDS, as defined by the proposed World Health Organisation (WHO) clinical staging system, who attended two Cape Town-based HIV clinics between 1984 and 1997. Patients were stratified according to the type of initial ADI. Survival associated with each opportunistic event was determined by Kaplan-Meier analysis. Cox proportional hazard analysis was used to determine relative risk for death associated with three strata of ADI. RESULTS: Median survival associated with various initial ADIs varied from less than 3 months (encephalopathy and wasting), to over 2 years (extrapulmonary tuberculosis and herpes simplex virus infection). This effect of ADI on outcome was most striking in patients with relatively preserved CD4 counts (CD4 > 50/microliter). A performance status score 4 predicted 50% mortality at 1 month, irrespective of co-morbidity. CONCLUSION: The type of ADI is an important determinant of survival, particularly in patients with preserved CD4 counts. The stratification of patients by type of ADI and performance status may be useful in the management of patients with advanced HIV infection in resource-limited environments.

AIDS Dementia Complex↗

Clinical efficacy with formoterol in the absence of a response to salmeterol: a review.

Salmeterol and formoterol are both beta 2-agonist bronchodilators with a long duration of action and are often classified together, yet they are distinctly different in their pharmacology. Recent evidence suggests there is a subpopulation of asthmatic patients who do not respond to salmeterol, yet can attain clinical benefit with formoterol. Following a literature search, three published case reports are reviewed as well as results from two published clinical trials designed specifically to document response to formoterol in 'non-responders to salmeterol' asthmatics. Possible mechanisms underlying this observation are discussed, including pharmacological differences of the two drugs relating to agonism at the beta 2-receptor and to effect on nuclear transcription factors.

Albuterol↗

Predictors and prognostic value of oral hairy leukoplakia and oral candidiasis in South African HIV-infected patients.

BACKGROUND: Oral hairy leukoplakia and oral candidiasis diseases (OHL/OC) are common clinical manifestations of HIV/AIDS. Sparse literature exists from resource-limited countries on their incidence and impact on HIV-infected patients. OBJECTIVE: To determine the predictors and prognosis of OHL/OC in HIV-infected patients. METHODS: Patients were drawn from a cohort established in 1992 and prospectively followed until 1997 in the adult HIV clinics, University of Cape Town. Cox hazards regression models were fitted to determine the predictors of OHL/OC, and the association between OHL/OC and progression to AIDS and death. RESULTS: 218 patients presenting with OHL/OC at their initial clinic visit were excluded. 205/772 patients developed OHL/OC (27.8 cases/100 years). White ethnicity (hazard ratio [HR] = 1.73, 95% CI 1.23-2.33), CD4+ count < 200 cells/(L (HR = 2.55, 95% CI 1.89-3.45), total lymphocyte count < 1250 cells/(L (HR = 1.72, 95% CI 1.28-2.31) and WHO stage 3 or 4 (HR = 2.61, 95% CI = 1.93-3.53) where variables predictive of increased hazard to developing OHL/OC. OHL/OC were independently associated with hazard of AIDS (HR = 3.65, 95% CI 1.89-6.69) and death (HR = 2.12, 95% CI 1.47-4.34). CONCLUSIONS: The presence of OHL/OC in HIV-infected patients provides important prognostic information, and can be used as a cost-effective tool for screening patients in therapeutic interventions in resource-limited settings.

AIDS-Related Opportunistic Infections↗

A novel series of 4-piperidinopyridine and 4-piperidinopyrimidine inhibitors of 2,3-oxidosqualene cyclase-lanosterol synthase.

A novel series of 4-piperidinopyridines and 4-piperidinopyrimidines showed potent and selective inhibition of rat 2,3-oxidosqualene cyclase-lanosterol synthase (OSC) (e.g. 26 IC(50) rat = 398 +/- 25 nM, human = 112 +/- 25 nM) and gave selective oral inhibition of rat cholesterol biosynthesis (26 ED(80) = 1.2 +/- 0.3 mg/kg, n = 5; HMGCoA reductase inhibitor simvastatin ED(80) = 1.2 +/- 0.3 mg/kg, n = 5). The piperidinopyrimidine OSC inhibitors have a significantly lower pK(a) than the corresponding pyridine or the previously reported quinuclidine OSC inhibitor series. This indicates that other novel OSC inhibitors may be found in analogues of this series across a broader pK(a) range (6.0-9.0). These series may yield novel hypocholesterolemic agents for the treatment of cardiovascular disease.

Administration, Oral↗

Risk factors for developing tuberculosis in HIV-1-infected adults from communities with a low or very high incidence of tuberculosis.

OBJECTIVE: To estimate the incidence rate of tuberculosis in HIV-1-infected adults resident in a region with a high tuberculosis prevalence and to identify clinical and laboratory parameters associated with increased risk of developing tuberculosis. METHODS: Adult patients going to the University of Cape Town HIV clinics between January 1986 and May 1996. The following variables were assessed for the risk of developing tuberculosis: ethnicity, employment and education status, World Health Organization (WHO) clinical stage, erythrocyte sedimentation rate (ESR), CD4+ count, and total lymphocyte count. Tuberculin skin test data were not available. RESULTS: There were 198 prevalent and 144 incident cases of tuberculosis in the cohort of 1206 patients. The incidence rate of tuberculosis risk was 10.4/100 person years. WHO clinical stages 3 and 4 (risk ratio [RR], 3.4; 95% confidence interval [CI], 1.8-6.4), ESR >75 mm/hour (RR, 3.5; CI, 1.8-6.5) and being a member of a high-prevalence tuberculosis community (RR, 2.5; CI, 1.2-5.1) were independently associated with the risk of developing tuberculosis. CONCLUSIONS: HIV-infected adults in Cape Town are at high risk of developing tuberculosis irrespective of tuberculin skin testing. The risk increases markedly with HIV disease progression. Patients at extremely high risk can be identified on the basis of demographic and clinical features. Such individuals would be suitable for targeted tuberculosis prophylaxis.

Adult↗

Corneal insult affects the production and distribution of FGF-2 within the lacrimal gland.

The purpose of this study was to determine the distribution of FGF-2 within rabbit lacrimal glands and to determine whether corneal insult affects that distribution. The scarified corneas of experimental animals were inoculated either with adenovirus type 5 or buffer. Control animals were either untreated, or animals whose corneas were scarified. Twenty-one days later all animals were killed and the lacrimal glands were studied by immunocytochemistry and Western blotting to detect FGF-2. In untreated control animals, FGF-2 was immunolocalized predominantly within a population of elongated cells in the basal epithelium of ducts, and to a lesser degree in the basal epithelium of the acini. The elongated immunopositive cells appear to be myoepithelial cells known to be present at these sites. Interstitial cells around ducts and acini, and the basement membranes of the ducts and acini, were also immunopositive for FGF-2. Twenty-one days after adenovirus inoculation and scarification of the cornea, immunopositivity for FGF-2 was dramatically decreased in basement membranes, but increased within myoepithelial cells of the duct epithelium. These myoepithelial cells were frequently enlarged, bulging toward the duct lumen. In animals whose corneas were inoculated with buffer and scarified, or animals whose corneas were simply scarified, the changes in the lacrimal gland were similar, but somewhat less pronounced, to those of adenovirus-inoculated animals. Western blots confirmed the presence of FGF-2 immunoreactivity in all groups. The major band in untreated controls was at 24 kD, whereas all animals with corneal scarification had major bands at 38 kD. Densitometry of Western blots demonstrated that the amount of 24 kD FGF-2 present within the lacrimal gland after corneal scarification was at least 50% less than in untreated controls, whereas 38 kD FGF-2 was at least ten-fold greater. Our findings indicate that corneal scarification results in an altered distribution of FGF-2 within the lacrimal gland, which involves a decrease in low molecular weight FGF-2 and a dramatic increase in a higher molecular weight isoform of FGF-2. FGF-2 may be released from myoepithelial cells apically (exocrine) into the tear fluid and basally (autocrine/paracrine) into the connective tissue, as well as from extracellular complexes within basal laminae.

Adenoviridae Infections↗

Distribution of growth factors and immune cells are altered in the lacrimal gland during pregnancy and lactation.

We have undertaken a series of studies to elucidate the roles of growth factors (FGF-2, EGF, TGF-beta1) and prolactin (PRL) in lacrimal gland function during pregnancy and lactation, and to better understand the status of the immune system within the lacrimal gland during those physiological states. In this initial study, lacrimal glands of pregnant (d15, d29), lactating (9d, 22d), and adult female control rabbits, were evaluated by immunohistochemistry, Western blotting and image analysis. In control rabbits EGF, TGF-beta1, and PRL, were immunolocalized primarily in the apical cytoplasm of intralobular ductal epithelial cells, and acini demonstrated a basement membrane-associated immunopositivity for TGF-beta1. FGF-2 immunolocalized in myoepithelial cells in the basal ductal epithelium and complexed to the basement membrane enclosing ducts and acini. Cells immunopositive for immune cell markers (RTLA and CD18) were apparent primarily around interlobular ducts. In d29 pregnant rabbits immunopositivity for EGF and TGF-beta1 was increased within intralobular ducts, both apically and basally, and within some interlobular ductal epithelial cells. Immunopositivity for PRL was strongest in d29 pregnant rabbits within the apical and basal cytoplasm of intralobular ductal epithelial cells. Immunopositivity for FGF-2 in myoepithelial cells was strong in d15 and d29 pregnant rabbits, although basement membrane-associated immunopositivity around acini was often decreased. Immunostaining for EGF and TGF-beta1 in lactating rabbits was similar to that in d29 pregnant rabbits, although basement membrane-associated immunopositivity around acini was more comparable to controls. By 22d lactation immunopositivity for FGF-2 closely resembled that in controls. Image analysis of pregnant and lactating rabbits demonstrated that cells immunopositive for RTLA and CD18 were less abundant around ducts and more abundant between acini, although in 22d lactating rabbits the size of periductal foci was increased to nearly that of controls. Western blots correlated well with the immunohistochemistry. Our findings demonstrate that pregnancy and lactation are accompanied by a shift in the distributions of growth factors and PRL, suggestive of increased release both apically into the lacrimal fluid and basally into the interstitium. Additional shifts in the distributions of cells of the immune system from periductal foci to interacinar sites suggest that there is a recruitment of immune cells away from ducts and toward the connective tissue interstitium surrounding the acini, possibly as part of a heightened state of immune readiness during pregnancy and lactation.

Animals↗

Evening report.

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Illinois↗

Diagnosing HIV-associated tuberculosis: reducing costs and diagnostic delay.

SETTING: University-affiliated hospital in South Africa. OBJECTIVE: To assess the time to diagnosis and the yield and laboratory cost of diagnostic procedures in human immunodeficiency virus (HIV) associated tuberculosis. DESIGN: Cohort study. PATIENTS: Adult HIV-infected patients with newly-diagnosed tuberculosis admitted over a 2-year period. RESULTS: A total of 141 admissions fulfilled the case definition. Sputum smear yield (43% overall) correlated strongly with chest radiograph appearance but not with CD4+ lymphocyte count. Sputum smear yield was approximately 40% per sample sent, resulting in a high cumulative yield when > or = three samples were sent. Smear of sputum or wide needle lymph node aspirates were the most cost-effective diagnostic methods. Significant diagnostic delay occurred in sputum smear-negative patients. Most patients with sputum smear-negative tuberculosis had either pleural effusions or lymphadenopathy. Lymph node biopsy had a high diagnostic yield even in patients with symmetrical nodes, but was under-utilised in this group. There was unnecessary expenditure on cultures, with many patients having several positive cultures. CONCLUSION: Repeated sputum smear examination produces a high cumulative yield in HIV-associated tuberculosis. Considerable savings in laboratory utilisation and bed occupancy would have been made if a streamlined diagnostic approach with greater use of lymph node aspirate and early pleural or lymph node biopsy had been followed.

Adult↗