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Biomedical subjects

D L Scott

Publications and source records attributed to D L Scott.

At least 109 records · Page 6Linked to original sources
PubMed1994

DC-ART: preventing or significantly decreasing the rate of progression of structural joint damage.

Progressive joint damage, increasing deformity, and declining function characterize rheumatoid arthritis (RA). The evidence suggests structural joint damage is the predominant cause of functional impairment. Structural changes of joints are evaluated by imaging methods. Plain joint radiographs remain the best method for determining the extent and nature of structural changes at present. Newer technologies such as magnetic resonance imaging may eventually replace them. Clinical studies of antirheumatic drugs involving the assessment of prevention or significant decrease in the rate of progression of structural joint damage in RA should meet several standards. All patients who enter a study, whether they continue medication or not, must be assessed on its completion. Studies require sufficient power to determine realistic differences due to therapy. They should last long enough for a reliable analysis of the effects of joint damage; 1 year would be the minimal period for such a study, and 2 years would be preferable. Evaluation should concentrate on erosions and related structural changes in juxtaarticular bone; mapping osteoporotic areas in early disease may be a sensitive and objective measure. Assessments ought to use changes within the hands and wrists to indicate overall progression, with the feet included in evaluating early disease. There should be different therapeutic aims at various stages of RA, focussing on preventing new erosions developing in early disease (< 2 years from diagnosis), preventing new erosions occurring in established disease (2-5 years from diagnosis), reducing the rate erosions develop in established disease (< 5 years from diagnosis), and reducing the rate of joint destruction in late disease (> 5 years from diagnosis).

Antirheumatic Agents↗
PubMed1994

Guidelines for use of antirheumatic drugs.

The Vth WHO/ILAR Task Force Meeting on Rhemuatic Diseases ratified guidelines for the use of antirheumatic drugs. Indications for use, contraindications, dose, administration and other usage principles, toxicity, and advice to patients have been agreed for analgesics, nonsteroidal antiinflammatory drugs, slower acting antirheumatic drugs, corticosteroids, and hypouricemic agents.

Adrenal Cortex Hormones↗
PubMed1994

Sex differences in inflammation induced cartilage damage in rodents. The influence of sex steroids.

OBJECTIVE: To investigate sex differences in granulomatous inflammation and its effects upon articular cartilage and to assess the potential role of sex steroids in the process. METHODS: The cotton-pellet cartilage implant model was used with male and female mice in the presence and absence of gonadectomy and hormone replacement. The effects of granulomatous tissue upon articular cartilage was assessed and tissue content of interleukin 1 (IL-1) was determined. The expression of sex hormone receptors in inflammatory tissue was investigated by immunocytochemistry. RESULTS: Female mice showed a higher ability than males to degrade cartilage irrespective of the sex of the cartilage implanted. Gonadectomy resulted in a significant acceleration of cartilage damage in both sexes, which was reverted by estrogen replacement in females and androgen replacement in males. Female granulomata had significantly higher IL-1 content than those from males. Gonadectomy was associated with an increased IL-1 content in males but not in females, the effects being abolished by androgen replacement in males. Estrogen and androgen receptors were identified in inflammatory cells from the granulomatous tissue. CONCLUSION: Our data demonstrate that sex hormones affect inflammation induced cartilage degradation in male and female mice probably through the modulation of cytokine production and release in the granulomatous tissue. Further investigation on the effects of sex steroids in inflammation induced cartilage degradation may help elucidate their pathogenic role and therapeutic potential in human disease.

Animals↗
PubMed1994

Developmental analysis of bone tumors in polyomavirus transgenic mice.

BACKGROUND: Transgenic mice carrying the polyoma (Py) early region gene develop both vascular and bone tumors that express the transgene (R. Wang and V. L. Bautch, J. Virol. 65:5174-5183, 1991). To determine the correlation between bone tumor formation and transgene expression, mice of two lines that showed differences in tumor pattern were analyzed. EXPERIMENTAL DESIGN: Py DNA encoding the early region gene was inserted into B6D2F1 mouse embryos. Transgenic mice were sacrificed at appropriate times in development, and the histopathology of the skulls and genotype analyses were performed independently. Py transgene expression was assayed in individual skulls or small groups of skulls. RESULTS: In mice of the Py-4 line, Py oncogene expression was detectable in skulls from 14.5 days of development. These mice had normal skulls at birth, and they developed lesions histologically resembling osteosarcoma synchronously 1 to 2 weeks after birth. Mice of the Py-3 line did not express detectable levels of transgene at 3 weeks of age, and they did not develop detectable skull pathology at this age. Less than 20% of adult Py-3 mice developed calvarial osteosarcoma-like lesions, and a similar number of these mice expressed the transgene in the skull. CONCLUSIONS: These data show that Py transgene expression in bone of the skull is differentially regulated in mice of the two lines, and they indicate that epigenetic changes may be sufficient to complement expression of the Py oncogene in neoplastic bone formation during development.

Animals↗
PubMed1993

Inflammation-induced cartilage degradation in female rodents. Protective role of sex hormones.

OBJECTIVE: To investigate the effects of physiologic levels of sex steroids on inflammation and cytokine production and their consequential cartilage degradation. METHODS: We used an in vivo model of inflammation-induced cartilage degradation in female mice to study the effects of ovariectomy and hormone treatment, and in vitro culture systems to examine the influence of sex steroids on cartilage metabolism, interleukin-1 (IL-1) production by granulomatous tissue, and its effects on female mouse articular cartilage. RESULTS: Ovariectomy resulted in accelerated cartilage breakdown associated with increased production of IL-1 by granulomatous tissue. The effects of ovariectomy on cartilage were reversed by treatment with estradiol and androgen, but not by progesterone treatment. Estradiol and progesterone reduced both spontaneous and IL-1-induced cartilage degradation in vitro. Testosterone antagonized the effects of IL-1 on both proteoglycan loss and proteoglycan synthesis. CONCLUSION: These data suggest that sex steroids have an important influence on inflammation-induced cartilage breakdown in female animals, with protective effects of both estradiol and androgens. Multiple mechanisms may be involved, and they are likely to include direct immunomodulatory effects as well as interactions with the effects of cytokine and of the glucocorticoid response to inflammation.

Animals↗
PubMed1993

The extracellular matrix of reparative tissue in the vitreous: fibronectin production in proliferative diabetic retinopathy membranes.

In a preliminary investigation into the origins of the extracellular matrix glycoprotein fibronectin in proliferative diabetic retinopathy (PDR) membranes, four globes containing PDR membranes were subjected to in situ hybridisation and immunohistochemical studies. Fibronectin mRNA was found in PDR membrane cells in two of the four globes. The fibronectin-producing cells exhibited fibroblast-like or macrophage-like morphology. Occasional intraretinal macrophage-like cells which contained fibronectin mRNA were also observed in three of the eyes. Variable fibronectin immunoreactivity was observed in all the PDR membranes, while the fibronectin staining pattern in the underlying retina was similar to that reported for albumin in eyes with breakdown of the blood-retina barrier. The findings suggest that fibronectin in PDR membranes originates from both plasma-derived fibronectin and the membrane cells, and support the concept that extracellular matrix components play an important role in PDR membrane progression.

Aged↗
PubMed1993

The prevention and healing of acute non-steroidal anti-inflammatory drug-associated gastroduodenal mucosal damage by misoprostol.

This double-blind study assessed the acute development of NSAID-associated gastroduodenal (GD) damage and its prevention by misoprostol. Patients requiring chronic NSAID therapy were stratified into two groups depending on initial endoscopic appearance, Group I: normal (n = 223); Group II: non-ulcer lesions (n = 78). After 2 weeks of therapy with NSAID and either misoprostol 400-800 micrograms daily or placebo the incidence of severe mucosal damage (including ulcers) was significantly reduced by misoprostol (odds ratio; 95% CI). Group I: 4.52; 1.94, 10.51 (P = 0.018); Group II: 10.93; 1.09, 109.60 (P = 0.014); Groups I and II combined: 5.95; 3.23, 10.94 (P = 0.0003). Misoprostol exerted a significant protective effect against progression of minor to severe damage in Group II (P < 0.001). Endoscopic findings did not correlate significantly with gastrointestinal symptoms and misoprostol did not interfere with the NSAID efficacy. Significant GD damage occurs early in the course of NSAID treatment and misoprostol significantly reduces the incidence of such damage.

Adult↗
PubMed1993

The long-term use of D-penicillamine for treating rheumatoid arthritis: is continuous therapy necessary?

Patients with RA often fail to comply with their therapy. We investigated the extent of non-compliance with D-penicillamine therapy and also whether patients needed continuous treatment after they had shown a therapeutic response. We developed a simple urinary test, measuring cysteine-penicillamine mixed disulphide by a high performance liquid chromatography technique, as an indicator of compliance. Using this method we evaluated compliance in 59 consecutive RA patients attending rheumatology outpatients for monitoring of D-penicillamine therapy. Evidence of poor compliance was shown in 39%. There was no relationship between poor compliance and disease activity. A possible explanation for this paradox emerged from a therapeutic study of the efficacy of intermittent treatment in patients in partial clinical remission on long-term D-penicillamine. In 14 randomly selected patients the daily dose of D-penicillamine was reduced in frequency over 6 months from 250-750 mg daily to the same dose taken 1 week out of every 4. The patients were compared to matched controls who remained on continuous therapy. After 30 months both the intermittent and continuous therapy groups had similar clinical and laboratory scores for disease activity. Our results suggest that many patients may not comply with their prescribed D-penicillamine regime, but such variation in compliance may not be clinically important since intermittent treatment may sustain response in the longer term.

Adult↗
PubMed1993

Cartilage degradation by polymorphonuclear leucocytes: in vitro assessment of the pathogenic mechanisms.

Polymorphonuclear leucocytes (PMNs), which predominate in inflammatory synovial fluid, can degrade cartilage. This was measured by a novel in vitro model; PMNs were incubated for up to one hour with 2 or 3 microns sections of cartilage and the glycosaminoglycan loss determined by microdensitometry after alcian blue staining. Glycosaminoglycan loss could be as a result of damage from reactive oxygen species, proteolytic enzymes, or a combination of the two. The relative contributions of these mechanisms were evaluated using selective inhibitors. The results show that activated PMNs will degrade cartilage and that this degradation is due to proteolytic enzymes and not reactive oxygen species. There is a specificity involving elastase but not other serine proteases. It is suggested that enzyme inhibition may play a part in reducing PMN mediated cartilage damage.

Animals↗
PubMed1993

Protective effect of androgens against inflammation induced cartilage degradation in male rodents.

OBJECTIVES: Rheumatoid arthritis (RA) is a disease which predominantly affects women. Interestingly, low serum androgen levels and clinical improvement with androgen replacement have been reported in male patients. The aetiopathogenic role of sex hormones in arthritis and their potential long term effects on joint destruction and disability remains unclear, however. This study was designed to investigate the potential influence of sex hormones on inflammation induced cartilage degradation in male rodents. METHODS: An in vivo model of cotton wrapped cartilage implants was used to assess the effects of androgen, oestradiol, and progesterone on inflammation induced cartilage degradation, and in vitro techniques were used to investigate the direct actions on cartilage metabolism and cytokine production in male animals. RESULTS: Orchidectomy resulted in accelerated cartilage damage which was reversed by replacement of physiological levels of androgens. Granulomatous tissue from castrated male rodents produced higher amounts of interleukin 1. Sex hormones reduced spontaneous proteoglycan loss in vitro but did not interfere with the effects of interleukin 1 on cultured cartilage. CONCLUSIONS: Androgens appear to protect cartilage from inflammation induced breakdown in male animals. These results support a pathogenic role for hypoandrogenism in rheumatoid arthritis and suggest that long term androgen replacement may help prevent joint damage and disability.

Androgens↗