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Biomedical subjects

George D Kitas

Publications and source records attributed to George D Kitas.

9 recordsLinked to original sources

Avoidance of unhealthy fattening: a longstanding proposal.

Diverse customary patterns of eating, drinking or movement are hypothesised to be effective in weight control based on laboratory experiments or theoretical calculations, in some cases supported by ecologically valid evidence. This method is applicable to healthy members of the public and to patients at high risk of and from obesity such as those having type-2 diabetes or chronic arthritis. Weight-reducing behaviour not adequately identified in current best practice educational messages includes: integration of exercise into desk-based employment; uses of stairs; uncompensated vigorous activity or reduction in amount eaten at a meal; protein level and carbohydrate timing in meals; having a "snack". This paper presents the scientific parts of a request for funds to integrate a suite of research methods based on theoretical models that can be applied to identify further, culturally and locally specific eating customs that avoid overweight and reduce obesity and can be iterated in a continuous (re)development of evidence-based expert advice and self-care practices in health and chronic disease.

Body Weight↗

Homocysteine from endothelial cells promotes LDL nitration and scavenger receptor uptake.

We recently reported that methionine-loaded human umbilical vein endothelial cells (HUVECs) exported homocysteine (Hcy) and were associated with hydroxyl radical generation and oxidation of lipids in LDL. Herein we have analysed the Hcy-induced posttranslational modifications (PTMs) of LDL protein. PTMs have been characterised using electrophoretic mobility shift, protein carbonyl ELISA, HPLC with electrochemical detection and Western blotting of 3-nitrotyrosine, and LDL uptake by scavenger receptors on monocyte/macrophages. We have also analysed PTMs in LDL isolated from rheumatoid (RA) and osteo-(OA) arthritis patients with cardiovascular disease (CVD). While reagent Hcy (< 50 microM) promoted copper-catalysed LDL protein oxidation, Hcy released from methionine-loaded HUVECs promoted LDL protein nitration. In addition, LDL nitration was associated with enhanced monocyte/macrophage uptake when compared with LDL oxidation. LDL protein nitration and uptake by monocytes, but not carbonyl formation, was elevated in both RA and OA patients with CVD compared with disease-matched patients that had no evidence of CVD. Moreover, a direct correlation between plasma total Hcy (tHcy) and LDL uptake was observed. The present studies suggest that elevated plasma tHcy may promote LDL nitration and increased scavenger receptor uptake, providing a molecular mechanism that may contribute to the clinical link between CVD and elevated plasma tHcy.

Adult↗

Inflammation and atherosclerosis in rheumatoid arthritis.

Rheumatoid arthritis (RA) associates with increased cardiovascular mortality. This appears to be predominantly due to ischaemic causes, such as myocardial infarction and congestive heart failure. The higher prevalence of cardiac ischaemia in RA is thought to be due to the accelerated development of atherosclerosis. There are two main reasons for this, which might be inter-related: the systemic inflammatory load, characteristic of RA; and the accumulation in RA of classical risk factors for coronary heart disease, which is reminiscent of the metabolic syndrome. We describe and discuss in the context of RA the involvement of local and systemic inflammatory processes in the development and rupture of atherosclerotic plaques, as well as the role of individual risk factors for coronary heart disease. We also present the challenges facing the clinical and scientific communities addressing this problem, which is receiving increasing attention.

Animals↗

Well-being in rheumatoid arthritis: the effects of disease duration and psychosocial factors.

This study examined the multivariate relationships of psychosocial factors with well-being in rheumatoid arthritis (RA). Fifty-five patients with early RA ( seven years) completed questionnaires on psychosocial factors and psychological and physical well-being. Illness perceptions related to worse depression and life satisfaction (especially in early RA) and to longer morning stiffness (especially in intermediate RA). Optimism related to lower pain in early and intermediate RA. Social support related to lower fatigue in established RA. Indications for interventions targeted by disease duration are discussed.

Adult↗

An assessment of back pain and the prevalence of sacroiliitis in sarcoidosis.

OBJECTIVES: Sarcoidosis is a chronic granulomatous multisystem disease in which arthritis is relatively common. Arthritis of the sacroiliac joints (sacroiliitis) has been described in sarcoidosis but is thought to be rare. The objective of this study was to determine the prevalence of sacroiliitis in a secondary-care population of patients with sarcoidosis. METHODS: Patients attending a specialist secondary-care sarcoidosis clinic underwent evaluation of spinal symptoms using a standard back pain questionnaire, examination of spinal mobility, and laboratory measurements of erythrocyte sedimentation rate, C-reactive protein, serum angiotensin-converting enzyme, and neopterin/creatinine ratio. Tissue typing for the presence of the human leukocyte antigen (HLA)-B27 allele was undertaken. Radiographs of the sacroiliac joints were obtained in each patient and reviewed independently by two observers; a further observer reviewed disputed radiographs. RESULTS: Sixty-one patients completed the assessments (80.3% of all patients invited to participate). Forty-nine of 61 patients (80.3%) reported having back pain at some point in their lives. Thirty-one of 61 patients (50.8%) had a score on the back pain questionnaire suggestive of inflammatory spinal disease, but only 3 of these patients had erosive damage of the sacroiliac joints on radiography indicating sacroiliitis. One further patient had erosive damage on radiography, making a total of four individuals with evidence of sacroiliitis, a prevalence of 6.6%. Four patients (one patient with sacroiliitis) were positive for HLA-B27. The back pain questionnaire had a sensitivity of 75% and a specificity of 51% for sacroiliitis in this population. CONCLUSION: The prevalence of spondyloarthropathy in the normal population has been estimated to be 1.9%. In the sarcoid population studied the prevalence was 6.6% suggesting a possible association between these two conditions. The standard back pain questionnaire for the identification of inflammatory spinal disease had a low sensitivity and specificity in this population.

Arthritis↗

Predictive value of antibodies to cyclic citrullinated peptide in patients with very early inflammatory arthritis.

OBJECTIVE: To study the prognostic value of antibodies to cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF), alone and in combination, in patients with very early synovitis. METHODS: A cross-sectional study was performed in patients with established inflammatory and noninflammatory disease to validate the assay in our unit and confirm previously reported sensitivities and specificities of anti-CCP antibodies. Subsequently, patients with synovitis of 3 months' duration were followed for 72 weeks and the ability of anti-CCP antibodies and RF to predict the development of rheumatoid arthritis (RA) and persistent inflammatory arthritis was assessed. RESULTS: One hundred twenty-four patients were assessed in the initial cross-sectional study. Anti-CCP antibodies and RF were detected by ELISA in only 4% of patients with non-RA inflammatory disease and in no patient with noninflammatory disease. Ninety-six patients with very early synovitis were assessed longitudinally. In these patients with early arthritis, the combination of anti-CCP antibodies and RF had a specificity, positive predictive value (PPV), sensitivity, and negative predictive value (NPV) for a diagnosis of RA of 100%, 100%, 58%, and 88%, respectively. The specificity, PPV, sensitivity, and NPV of this antibody combination for the development of persistent disease-fulfilling classification criteria for RA were 97%, 86%, 63%, and 91%, respectively. CONCLUSION: In patients with synovitis of 3 months' duration, a combination of anti-CCP antibodies and RF has a high specificity and PPV for the development of persistent RA. This autoantibody combination can be used to identify patients with disease destined to develop RA who may be appropriate for very early intervention.

Adult↗

Reversing myocardial microvascular disease in a patient with rheumatoid arthritis.

Rheumatoid arthritis (RA) is associated with increased cardiovascular mortality. This is regarded as being due to accelerated coronary atherosclerosis. We describe a 62-year-old man with seropositive erosive RA and extraarticular manifestations but no history of cardiovascular disease. Noninvasive assessment of myocardial blood flow by adenosine stressed thallium scanning showed reversible ischemia and diffusely poor myocardial perfusion. Repeat assessment after intensive immunosuppression for rheumatoid vasculitis revealed resolution of the ischemic changes and generally increased myocardial perfusion. Coronary angiography revealed no significant atheroma, suggesting that myocardial microvascular disease was responsible for the ischemia. This may be an important determinant of cardiovascular outcome in RA, and this case indicated that it can be reversed with immunosuppression.

Arthritis, Rheumatoid↗

Validation of a novel ELISA for measurement of MDA-LDL in human plasma.

The involvement of oxidatively modified low density lipoprotein (LDL) in the development of CHD is widely described. We have produced two antibodies, recognizing the lipid oxidation product malondialdehyde (MDA) on whole LDL or ApoB-100. The antibodies were utilized in the development of an ELISA for quantitation of MDA-LDL in human plasma. Intra- and inter-assay coefficients of variation (% CV) were measured as 4.8 and 7.7%, respectively, and sensitivity of the assay as 0.04 micro g/ml MDA-LDL. Recovery of standard MDA-LDL from native LDL was 102%, indicating the ELISA to be specific with no interference from other biomolecules. Further validation of the ELISA was carried out against two established methods for measurement of lipid peroxidation products, MDA by HPLC and F(2)-isoprostanes by GC-MS. Results indicated that MDA-LDL is formed at a later stage of oxidation than either MDA or F(2)-isoprostanes. In vivo analysis demonstrated that the ELISA was able to determine steady-state concentrations of plasma MDA-LDL (an end marker of lipid peroxidation). A reference range of 34.3 +/- 8.8 micro g/ml MDA-LDL was established for healthy individuals. Further, the ELISA was used to show significantly increased plasma MDA-LDL levels in subjects with confirmed ischemic heart disease, and could therefore possibly be of benefit as a diagnostic tool for assessing CHD risk.

Adolescent↗