Epidemiological and experimental studies have shown that hyperuricaemia and gout are intricately ... more Epidemiological and experimental studies have shown that hyperuricaemia and gout are intricately linked with hypertension, metabolic syndrome, chronic kidney disease and cardiovascular disease. A number of studies suggest that hyperuricaemia and gout are independent risk factors for the development of these conditions and that these conditions account, in part, for the increased mortality rate of patients with gout. In this Review, we first discuss the links between hyperuricaemia, gout and these comorbidities, and present the mechanisms by which uric acid production and gout might favour the development of cardiovascular and renal diseases. We then emphasize the potential benefit of urate-lowering therapies on cardiovascular and renal outcomes in patients with hyperuricaemia. The mechanisms that link elevated serum uric acid levels and gout with these comorbidities seem to be multifactorial, implicating low-grade systemic inflammation and xanthine oxidase (XO) activity, as well as the deleterious effects of hyperuricaemia itself. Patients with asymptomatic hyperuricaemia should be treated by nonpharmacological means to lower their SUA levels. In patients with gout, long-term pharmacological inhibition of XO is a treatment strategy that might also reduce cardiovascular and renal comorbidities, because of its dual effect of lowering SUA levels as well as reducing free-radical production during uric acid formation.
Vol. 9 -I987 Pharmaceutisch Weekblad Scienttfic Edition officinale L. species complex and S. aspe... more Vol. 9 -I987 Pharmaceutisch Weekblad Scienttfic Edition officinale L. species complex and S. asperum Lepech. Part n. Phytosterols and triterpe.noids. Plant Syst Evol z983;I43:285-92. Wichers H J, Ten Kate J, Buys CHCM, Huizing HJ. A simple and rapid procedure to obtain nucleated proto-z87 plasts from plant material. Cytologia I984;49: xo3-9. Huizing H J, R6der E, Wiedenfeld H. Die '~C-NMR-Daten des Pyrrolizidine-Alkaloids Echimidin. Arch Pharm (Weinheim) *985;3*8:476-7. clinical pharmacological meeting Organized by the
Journal of Veterinary Pharmacology and Therapeutics, 1989
metabolism and renal clearance of sulphatroxazole in calves and cows. J . vet. Phanacol. Therap. ... more metabolism and renal clearance of sulphatroxazole in calves and cows. J . vet. Phanacol. Therap. 12, 50-57.
Background: Randomised controlled trials (RCTs) evaluating the efficacy of antagonists to tumour ... more Background: Randomised controlled trials (RCTs) evaluating the efficacy of antagonists to tumour necrosis factor a (TNFa) showed high response percentages in the groups treated with active drugs. Objective: To compare the efficacy of anti-TNF treatments for rheumatoid arthritis (RA) patients in RCTs and in daily clinical practice, with an emphasis on the efficacy for patients eligible and not eligible for RCTs of anti-TNF treatments. Methods: First, randomised placebo-controlled trials written in English for etanercept, infliximab and adalimumab for patients with RA were selected by a systematic review. Second, the DREAM (Dutch Rheumatoid Arthritis Monitoring) register with patients starting for the first time on one of the TNF-blocking agents was used. Patient characteristics, doses of medication and co-medication as well as the ACR20 response percentages were compared between RCTs and DREAM data, stratified for trial eligibility. Results: In 10 of 11 comparisons, the ACR20 response percentages were lower in daily clinical practice than in the RCT active drug group, which was significant in five of 11 comparisons. Only 34-79% of DREAM patients fulfilled the selection criteria for disease activity in the several RCTs examined. DREAM patients eligible for RCTs had higher response percentages than ineligible DREAM patients. ACR20 response percentages of eligible DREAM patients were comparable with the ACR20 response percentages of the RCT active drug group in 10 of 11 comparisons. Conclusion: The efficacy of TNF-blocking agents in RCTs exceeded the efficacy of these drugs in clinical practice. However, in clinical practice more patients with lower disease activity were treated with TNFblocking agents compared with those treated in RCTs. For daily practice patients who were eligible for RCTs, responses were more similar to responses reached in RCTs.
Several studies point to a role of Toll-like receptors (TLRs) in the development of rheumatoid ar... more Several studies point to a role of Toll-like receptors (TLRs) in the development of rheumatoid arthritis (RA). We investigated if genetic variants in TLR genes are associated with RA and response to tumour necrosis factor blocking (anti-TNF) medication.
Epidemiological and experimental studies have shown that hyperuricaemia and gout are intricately ... more Epidemiological and experimental studies have shown that hyperuricaemia and gout are intricately linked with hypertension, metabolic syndrome, chronic kidney disease and cardiovascular disease. A number of studies suggest that hyperuricaemia and gout are independent risk factors for the development of these conditions and that these conditions account, in part, for the increased mortality rate of patients with gout. In this Review, we first discuss the links between hyperuricaemia, gout and these comorbidities, and present the mechanisms by which uric acid production and gout might favour the development of cardiovascular and renal diseases. We then emphasize the potential benefit of urate-lowering therapies on cardiovascular and renal outcomes in patients with hyperuricaemia. The mechanisms that link elevated serum uric acid levels and gout with these comorbidities seem to be multifactorial, implicating low-grade systemic inflammation and xanthine oxidase (XO) activity, as well as the deleterious effects of hyperuricaemia itself. Patients with asymptomatic hyperuricaemia should be treated by nonpharmacological means to lower their SUA levels. In patients with gout, long-term pharmacological inhibition of XO is a treatment strategy that might also reduce cardiovascular and renal comorbidities, because of its dual effect of lowering SUA levels as well as reducing free-radical production during uric acid formation.
Vol. 9 -I987 Pharmaceutisch Weekblad Scienttfic Edition officinale L. species complex and S. aspe... more Vol. 9 -I987 Pharmaceutisch Weekblad Scienttfic Edition officinale L. species complex and S. asperum Lepech. Part n. Phytosterols and triterpe.noids. Plant Syst Evol z983;I43:285-92. Wichers H J, Ten Kate J, Buys CHCM, Huizing HJ. A simple and rapid procedure to obtain nucleated proto-z87 plasts from plant material. Cytologia I984;49: xo3-9. Huizing H J, R6der E, Wiedenfeld H. Die '~C-NMR-Daten des Pyrrolizidine-Alkaloids Echimidin. Arch Pharm (Weinheim) *985;3*8:476-7. clinical pharmacological meeting Organized by the
Journal of Veterinary Pharmacology and Therapeutics, 1989
metabolism and renal clearance of sulphatroxazole in calves and cows. J . vet. Phanacol. Therap. ... more metabolism and renal clearance of sulphatroxazole in calves and cows. J . vet. Phanacol. Therap. 12, 50-57.
Background: Randomised controlled trials (RCTs) evaluating the efficacy of antagonists to tumour ... more Background: Randomised controlled trials (RCTs) evaluating the efficacy of antagonists to tumour necrosis factor a (TNFa) showed high response percentages in the groups treated with active drugs. Objective: To compare the efficacy of anti-TNF treatments for rheumatoid arthritis (RA) patients in RCTs and in daily clinical practice, with an emphasis on the efficacy for patients eligible and not eligible for RCTs of anti-TNF treatments. Methods: First, randomised placebo-controlled trials written in English for etanercept, infliximab and adalimumab for patients with RA were selected by a systematic review. Second, the DREAM (Dutch Rheumatoid Arthritis Monitoring) register with patients starting for the first time on one of the TNF-blocking agents was used. Patient characteristics, doses of medication and co-medication as well as the ACR20 response percentages were compared between RCTs and DREAM data, stratified for trial eligibility. Results: In 10 of 11 comparisons, the ACR20 response percentages were lower in daily clinical practice than in the RCT active drug group, which was significant in five of 11 comparisons. Only 34-79% of DREAM patients fulfilled the selection criteria for disease activity in the several RCTs examined. DREAM patients eligible for RCTs had higher response percentages than ineligible DREAM patients. ACR20 response percentages of eligible DREAM patients were comparable with the ACR20 response percentages of the RCT active drug group in 10 of 11 comparisons. Conclusion: The efficacy of TNF-blocking agents in RCTs exceeded the efficacy of these drugs in clinical practice. However, in clinical practice more patients with lower disease activity were treated with TNFblocking agents compared with those treated in RCTs. For daily practice patients who were eligible for RCTs, responses were more similar to responses reached in RCTs.
Several studies point to a role of Toll-like receptors (TLRs) in the development of rheumatoid ar... more Several studies point to a role of Toll-like receptors (TLRs) in the development of rheumatoid arthritis (RA). We investigated if genetic variants in TLR genes are associated with RA and response to tumour necrosis factor blocking (anti-TNF) medication.
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