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Biomedical subjects

T Gould

Publications and source records attributed to T Gould.

At least 19 recordsLinked to original sources

Systemic lupus erythematosus in a patient with human immunodeficiency virus infection--challenges in diagnosis and management.

Systemic lupus erythematosus (SLE) is mainly a disease of young women. The problem of coexistent human immunodeficiency virus (HIV) infection is a growing problem in sub-Saharan Africa. We describe a case of active life-threatening neuropsychiatric lupus in a patient with underlying HIV infection. The challenges of interpreting physical signs and laboratory features that are common to both conditions, and the dilemma of treating active SLE with cytotoxics in the immunocompromised patient, are discussed.

Adult↗

Socioeconomic differences in food purchasing behaviour and suggested implications for diet-related health promotion.

BACKGROUND: The relationship between socioeconomic position (SEP) and diet has been examined mainly on the basis of food and nutrient intake. As a complement to this work, we focused on the socioeconomic patterning of food purchasing, as many educational dietary messages emphasize behaviours such as food choice when shopping. Also, the type of food people buy influences the quality of their nutrient intake. METHODS: A probability sample of households in Brisbane City, Australia (n = 1003, 66.4% response rate). Data were collected using face-to-face interviews. SEP was measured using education, occupation and household income. Food purchasing was examined on the basis of grocery items (including meat and chicken) and fruit and vegetables. RESULTS: Significant associations were found between each socioeconomic indicator and food purchasing. Persons from socioeconomically disadvantaged backgrounds were less likely to purchase grocery foods that were comparatively high in fibre and low in fat, salt and sugar. The least educated, those employed in blue-collar (manual) occupations and residents of low income households purchased fewer types of fruit and vegetables, and less regularly, than their higher status counterparts. CONCLUSIONS: Health promotion efforts aimed at narrowing socioeconomic differences in food purchasing need to be designed and implemented with an understanding of, and a sensitivity to, the barriers to nutritional improvement that difficult life circumstances can impose.

Australia↗

Tenascin-C aptamers are generated using tumor cells and purified protein.

Tenascin-C (TN-C) is an extracellular matrix protein that is overexpressed during tissue remodeling processes, including tumor growth. To identify an aptamer for testing as a tumor-selective ligand, SELEX (systematic evolution of ligands by exponential enrichment) procedures were performed using both TN-C and TN-C-expressing U251 glioblastoma cells. The different selection techniques yielded TN-C aptamers that are related in sequence. In addition, a crossover procedure that switched from tumor cell to purified protein selections was effective in isolating two high-affinity TN-C aptamers. When targeting tumor cells in vitro, the observed propensity of naive oligonucleotide pools to evolve TN-C aptamers may be due to the abundance of this protein. In vivo, TN-C abundance may also be well suited for aptamer accumulation in the tumor milieu. A size-minimized and nuclease-stabilized aptamer, TTA1, binds to the fibrinogen-like domain of TN-C with an equilibrium dissociation constant (K(d)) of 5 x 10(-9) m. At 13 kDa, this aptamer is intermediate in size between peptides and single chain antibody fragments, both of which are superior to antibodies for tumor targeting because of their smaller size. TTA1 defines a new class of ligands that are intended for targeted delivery of radioisotopes or chemical agents to diseased tissues.

Animals↗

Antioxidant-rich diets improve cerebellar physiology and motor learning in aged rats.

The free radical theory of aging predicts that reactive oxygen species are involved in the decline in function associated with aging. The present paper reports that diets supplemented with either spinach, strawberries or blueberries, nutritional sources of antioxidants, reverse age-induced declines in beta-adrenergic receptor function in cerebellar Purkinje neurons measured using electrophysiological techniques. In addition the spinach diet improved learning on a runway motor task, previously shown to be modulated by cerebellar norepinephrine. Motor learning is important for adaptation to changes in the environment and is thus critical for rehabilitation following stroke, spinal cord injury, and the onset of some neurodegenerative diseases. These data are the first to indicate that age-related deficits in motor learning and memory can be reversed with nutritional interventions.

Aging↗

An analysis of excess mortality not predicted to occur by APACHE III in an Australian level III intensive care unit.

The APACHE III derived standardized mortality ratio has been suggested as a statistic to measure intensive care unit (ICU) effectiveness. From 1991 data collected on 519 consecutive admissions to the Royal Adelaide Hospital ICU a standardized mortality ratio of 1.25 was calculated. Of the 174 deaths only 95 had a prediction of death greater than 0.5. As part of a quality assurance study we undertook a retrospective case note audit to try to identify factors that were associated with the low mortality prediction (< 0.5) in hospital deaths. Firstly we analysed the patient population that died to determine the factors that were different between patients who had a mortality prediction of greater than 0.5 versus those who had a mortality prediction of less than 0.5. Next we analysed the patient population with a mortality prediction of less than 0.5 and compared actual survivors with patients who died in hospital. Amongst low mortality prediction patients admitted to the Royal Adelaide Hospital ICU we identified age, a history of acute myocardial infarction, presentation to ICU after a cardiac arrest or with an elevated creatinine and the development of acute renal failure and septicaemia during the ICU admission as being associated with in-hospital mortality. We also documented that late hospital deaths on the ward after ICU discharge occurred more frequently with low predicted hospital mortality ICU patients. Factors other than the APACHE III score may be associated with hospital deaths of ICU patients.

APACHE↗

Combination benefit of PEGylated soluble tumor necrosis factor receptor type I (PEG sTNF-RI) and dexamethasone or indomethacin in adjuvant arthritic rats.

OBJECTIVE: To determine the potential combination benefit receptor of treatment with PEGylated soluble tumor necrosis factor type I (PEG sTNF-RI) and dexamethasone (dex) or indomethacin (indo) in adjuvant arthritic rats. SUBJECTS: 160 male Lewis Rats. TREATMENT: PEG sTNF-RI, dex, indo. METHODS: Rats with adjuvant arthritis were given daily oral dex (0.025 or 0.006 mg/kg) or indo (0.5 or 0.25 mg/kg) day 9-14, alone or in combination with PEG sTNF-RI (sc on days 9, 11, and 13 of arthritis). Efficacy was monitored by volume measurement of ankle joints, final paw weights and histologic evaluation with particular emphasis on bone lesions. RESULTS: Treatment with 1 mg/kg PEG sTNF-RI alone resulted in 27% inhibition of final paw weights, dex alone (0.025 mg/kg) gave 25% inhibition and the combination resulted in 58% inhibition. Histologic evaluation of ankle joints demonstrated 48% inhibition of bone resorption with PEG sTNF-RI alone, 55% inhibition with dex alone and the combination treatment inhibited bone resorption by 100%. Inactive doses of PEG sTNF-RI (0.3 mg/kg) and dex (0.006 mg/kg) when combined resulted in 39% inhibition of paw swelling (AUC) and 39% inhibition of bone resorption. Combination treatment with indomethacin resulted in slight additive effects on inflammation parameters but no additive effects on bone resorption. CONCLUSION: Combination therapy with PEG sTNF-RI and dexamethasone results in additive or synergistic effects depending on the dose. Combination therapy with indomethacin resulted in slight additive effects on paw swelling parameters, but no additive benefit on bone resorption. Data from these studies support the clinical investigation of the use of combination therapy of PEG sTNF-RI and dex or other corticosteroids in rheumatoid arthritis patients.

Animals↗

Antiarthritic activity of soluble tumor necrosis factor receptor type I forms in adjuvant arthritis: correlation of plasma levels with efficacy.

OBJECTIVE: To determine the importance of tumor necrosis factor (TNF) in the pathogenesis of adjuvant disease in rats and to determine plasma levels of recombinant soluble TNF receptor type I (sTNF-RI) necessary for efficacy, to project dosing for human clinical trials. METHODS: Rats with adjuvant arthritis were treated by continuous infusion with sTNF-RI forms to maintain blood levels of this TNF-alpha inhibitory protein. In addition, rats were given bolus injections of polyethylene glycol linked sTNF-RI and efficacy and plasma levels were determined. Effects of treatment in the rats were monitored by sequential volume or diameter measurement of ankle joints, final paw weights, and histologic evaluation of ankle joints, with particular emphasis on bone erosive lesions. RESULTS: In all studies and regardless of dosing methodology (bolus vs continuous infusion), minimal plasma levels for efficacy were in the 0.3-0.5 microg/ml range. Higher plasma levels resulted in greater efficacy, with maximal effects achieved when plasma levels were in the 5 microg/ml range. Beneficial effects of treatment were seen on body weight, paw swelling, splenomegaly, hepatomegaly, and bone resorption. CONCLUSION: TNF-alpha is an important mediator of all aspects of rat adjuvant disease including both the destructive processes in the joints as well as the systemic manifestations of adjuvant disease. Studies using various forms of sTNF-RI consistently show that plasma levels of 0.3-0.5 microg/ml are required for minimal efficacy and that higher plasma levels show dose-responsive enhanced efficacy.

Animals↗

Hospital records--asset or liability?

Health records of different sorts have been shown--in one region--to cost 13m pounds a year, and to take up 10 miles of shelving. Across one region, records would take up the length of the M4. Terry Gould and colleagues describe a project to establish some protocols for sensible record keeping.

Costs and Cost Analysis↗

Selective attention skills in Alzheimer's disease: performance on graded cancellation tests varying in density and complexity.

Nine selective cancellation tasks were administered to nine subjects with Alzheimer's disease (AD), nine elderly control, and eight depressed subjects. Each task consisted of an 8 1/2 x 11 sheet of paper containing line drawings of geometric shapes that were identified as either targets or distractors. The nine forms of the task varied along two independent graded dimensions: (1) the total number of items in the field (Density: 3 levels) and (2) the number of different distractors in the surround (Complexity: 3 levels). Performance of the AD group was worse than that of the other groups, and performance for all groups declined with density. Error analysis of the impaired performance of the AD subjects showed that they made errors of omission that differed significantly as a function of density. There was no evidence that they could adopt a chunking strategy to accommodate the increased load.

Aged↗

Therapeutic problems arising from the use of the intravenous route for drug administration.

The kinetics of drug delivery were studied under conditions of varying iv flow rates and varying sites of drug administration into an iv system. The iv sites and rates were selected on the basis of questionnaire data obtained from nursing personnel. The rate of drug delivery from the iv system was dependent upon the iv flow rate and site of injection of the drug into the iv system. Under conditions of slow iv flow rates (3 ml/hour) there was the expected time delay required for the drug to begin to be infused but an unanticipated protracted time required for actual completion of the drug infusion. Calculation of theoretical drug blood levels based on the results of these iv studies revealed very different blood levels of drug at respective times, including different peak concentrations, depending on the iv flow rate and site at which the drug was injected into the system. Failure to appreciate the effects of slow iv rates and distal iv injection sites on actual rates of drug administration can adversely affect pharmacokinetic decisions and conceivably influence therapeutic success or failure.

Aminophylline↗

Prevalence and clinical correlates of anti-phospholipid antibodies in South Africans with systemic lupus erythematosus.

OBJECTIVE: To determine the prevalence and clinical correlates of anti-phospholipid antibodies (aPL), including anti-cardiolipin antibodies (aCL), lupus anti-coagulant (LA), anti-beta2-glycoprotein 1 (abeta2GP1), and anti-prothrombin (aPT) antibodies, in Black South African patients with systemic lupus erythematosus (SLE). METHODS: A cross-sectional study of 100 SLE patients in whom clinical characteristics, including features of the anti-phospholipid syndrome (APS), disease activity, and damage were documented, and sera tested for aCL, abeta2GP, and aPT of all isotypes, and LA. RESULTS: Positive aCL, abeta2GPI, aPT, and LA were found in 53, 84, 20, and 2 patients, respectively. Immunoglobulin (Ig)A aCL and IgG abeta2GPI were the commonest aCL (49.1%) and abeta2GPI (47%) isotypes, respectively. IgA abeta2GPI were associated with both a history of thrombosis alone (p<0.05) and a history of any clinical feature, thrombosis, and/or spontaneous abortion of the APS (p<0.05); IgA aCL were associated with a history of any clinical APS event (p<0.05); and abeta2GPI of any isotype were associated with a history of arthritis (p<0.001). CONCLUSION: Our findings provide further evidence that screening for abeta2GPI and IgA aCL isotypes may improve the risk assessment for APS in SLE patients of African extraction. Further prospective studies are warranted to determine the clinical utility of these tests and to elucidate the genetic basis for the increased IgA aPL response in SLE patients of African extraction.

Antibodies, Antinuclear↗

Animal models of arthritis: relevance to human disease.

Animal models of arthritis are used to evaluate potential antiarthritis drugs for clinical use. Therefore capacity of the model to predict efficacy in human disease is one of the most important criteria in model selection. Animal models of rheumatoid arthritis (RA) with a proven track record of predictability include rat adjuvant arthritis, rat type II collagen arthritis, mouse type II collagen arthritis, and antigen-induced arthritis in several species. Agents currently in clinical use (or trials) that are active in these models include corticosteroids, methotrexate, nonsteroidal anti-inflammatory drugs, cyclosporin A, leflunomide, interleukin-1 receptor antagonist, and soluble tumor necrosis factor receptors. For some of these agents, the models also predict that toxicities seen at higher doses for prolonged periods would preclude dosing in humans at levels that might provide disease-modifying effects. Animal models of osteoarthritis (OA) include mouse and guinea pig spontaneous OA, meniscectomy and ligament transection in guinea pigs, meniscectomy in rabbits, and meniscectomy and cruciate transection in dogs. None of these models have a proven track record of predictability in human disease because there are no agents that have been proven to provide anything other than symptomatic relief in human OA. Efficacy data and features of the various models of RA and OA are discussed with emphasis on their proven relevance to human disease.

Animals↗