Uso de infliximab en pacientes de un centro reumatologico / Use of infliximab in patients of a rheumatologic center

The objective of this study was to obtain post-marketing information about the use of infliximab in an ambulatory setting. We studied--retrospectively and prospectively--the case records of patients with rheumatoid arthritis (n=37), psoriatic arthritis (n=5), mixed connective tissue disease (n=1), and ankylosing spondylitis (n=2) who received infliximab (3 mg/kg) from August 2000 to January 2003. Descriptive values were given as percentage, mean or median, and standard deviation or interquartile range. Wilcoxon test was used for paired analysis of pre/post doses of corticosteroids, non-steroidal anti-inflammatory drugs, and methotrexate therapy. A p value < or = 0.05 was considered significant. Forty-five patients were included. A total of 207 infusions were administered. In 4 patients the treatment was permanently discontinued due to severe back pain during the infusion (2 cases) and serious anaphylactic reactions (2 cases). Other adverse reactions occurring during infusions were mild and successfully managed with standard treatment. A case of staphylococcal septic arthritis resolved with standard antibiotic treatment. No patient had evidence of active tuberculosis. One patient with rheumatoid arthritis and chronic renal insufficiency, received treatment with infliximab 1.9 mg/kg, every 30 days, with no changes in renal function. Due to improvement of symptoms, 14/39 (35.9%) patients could decrease the doses of corticosteroids, 15/43 (34.8%) decreased the doses of antiinflammatory drugs and 12/34 (35.3%) decreased methotrexate dosage. Although some questions remain to be elucidated, this case series shows the drug safety profile, the possibility to reduce concomitant drug doses, as well as individual approaches for situations where there are not yet guidelines available, so that rheumatologists have to make decisions based on clinical needs.

El objetivo de este estudio fue obtener informacion postmarketing sobre el uso de infliximab en un centro reumatologico de atencion ambulatoria. Se realizo un analisis retrospectivo y prospectivo de las historias clinicas de pacientes con diagnostico de artritis reumatoidea (n=37), artritis psoriasica (n=5),enfermedad mixta del tejido conectivo (n=1) y espondilitis anquilosante (n=2) que recibieron infliximab (3 mg/kg) desde agosto de 2000 a junio de 2003. El analisis descriptivo se realizo con porcentajes, media o medianay desviacion estandar o intervalo intercuartilo. La prueba de Wilcoxon se utilizo para el analisis apareado dedosis de antiinflamatorios no esteroideos y metotrexato, anterior y posterior a la administracion de infliximab. Se consideraron significativos valores de p < o = 0.05. Se incluyeron 45 pacientes a los que se les administraron un total de 207 infusiones. En 2 pacientes el infliximab se discontinuó debido a lumbalgia severa durante la infusion y en otros 2 por anafilaxia intrainfusional. Otras reacciones adversas ocurridas durante las infusiones fueron moderadas y respondieron adecuadamente al tratamiento estandar. Se presento un caso de artritis septica de rodilla por estafilococos. Un caso de artritis reumatoidea con insuficiencia renal compensada recibio infliximab en dosis de 1.9 mg/kg cada 30 dias, sin cambios en la funcion renal. Al momento, ningun paciente ha desarrollado tuberculosis activa. Debido a la mejoria clinica, se redujo la dosis de corticoides en 14/39 (35.9%) pacientes, de antiinflamatorios no esteroideos en 15/43 (34.8%) y de metotrexato en 12/34 (35.3%). En estaserie de casos se muestra el perfil de seguridad de infliximab, la posibilidad de reducir la dosis de drogas concomitantes,asi como algunos enfoques individuales sobre situaciones para las cuales no disponemos de guias basadas en la evidencia medica, y en las que los reumatologos debemos tomar decisiones segun las necesidades clinicas.

Uso de infliximab en pacientes de un centro reumatologico / Use of infliximab in patients of a rheumatologic center

The objective of this study was to obtain post-marketing information about the use of infliximab in an ambulatory setting. We studied--retrospectively and prospectively--the case records of patients with rheumatoid arthritis (n=37), psoriatic arthritis (n=5), mixed connective tissue disease (n=1), and ankylosing spondylitis (n=2) who received infliximab (3 mg/kg) from August 2000 to January 2003. Descriptive values were given as percentage, mean or median, and standard deviation or interquartile range. Wilcoxon test was used for paired analysis of pre/post doses of corticosteroids, non-steroidal anti-inflammatory drugs, and methotrexate therapy. A p value < or = 0.05 was considered significant. Forty-five patients were included. A total of 207 infusions were administered. In 4 patients the treatment was permanently discontinued due to severe back pain during the infusion (2 cases) and serious anaphylactic reactions (2 cases). Other adverse reactions occurring during infusions were mild and successfully managed with standard treatment. A case of staphylococcal septic arthritis resolved with standard antibiotic treatment. No patient had evidence of active tuberculosis. One patient with rheumatoid arthritis and chronic renal insufficiency, received treatment with infliximab 1.9 mg/kg, every 30 days, with no changes in renal function. Due to improvement of symptoms, 14/39 (35.9%) patients could decrease the doses of corticosteroids, 15/43 (34.8%) decreased the doses of antiinflammatory drugs and 12/34 (35.3%) decreased methotrexate dosage. Although some questions remain to be elucidated, this case series shows the drug safety profile, the possibility to reduce concomitant drug doses, as well as individual approaches for situations where there are not yet guidelines available, so that rheumatologists have to make decisions based on clinical needs.(AU)

El objetivo de este estudio fue obtener informacion postmarketing sobre el uso de infliximab en un centro reumatologico de atencion ambulatoria. Se realizo un analisis retrospectivo y prospectivo de las historias clinicas de pacientes con diagnostico de artritis reumatoidea (n=37), artritis psoriasica (n=5),enfermedad mixta del tejido conectivo (n=1) y espondilitis anquilosante (n=2) que recibieron infliximab (3 mg/kg) desde agosto de 2000 a junio de 2003. El analisis descriptivo se realizo con porcentajes, media o medianay desviacion estandar o intervalo intercuartilo. La prueba de Wilcoxon se utilizo para el analisis apareado dedosis de antiinflamatorios no esteroideos y metotrexato, anterior y posterior a la administracion de infliximab. Se consideraron significativos valores de p < o = 0.05. Se incluyeron 45 pacientes a los que se les administraron un total de 207 infusiones. En 2 pacientes el infliximab se discontinuó debido a lumbalgia severa durante la infusion y en otros 2 por anafilaxia intrainfusional. Otras reacciones adversas ocurridas durante las infusiones fueron moderadas y respondieron adecuadamente al tratamiento estandar. Se presento un caso de artritis septica de rodilla por estafilococos. Un caso de artritis reumatoidea con insuficiencia renal compensada recibio infliximab en dosis de 1.9 mg/kg cada 30 dias, sin cambios en la funcion renal. Al momento, ningun paciente ha desarrollado tuberculosis activa. Debido a la mejoria clinica, se redujo la dosis de corticoides en 14/39 (35.9%) pacientes, de antiinflamatorios no esteroideos en 15/43 (34.8%) y de metotrexato en 12/34 (35.3%). En estaserie de casos se muestra el perfil de seguridad de infliximab, la posibilidad de reducir la dosis de drogas concomitantes,asi como algunos enfoques individuales sobre situaciones para las cuales no disponemos de guias basadas en la evidencia medica, y en las que los reumatologos debemos tomar decisiones segun las necesidades clinicas.(AU)

Association analysis of genotypic frequencies of matrilin-1 gene in patients with osteoarthritis.

OBJECTIVE: It has been suggested that genotypic variation in the gene which encodes the matrilin-1 (MATN-1) protein may be involved in the development of hip osteoarthritis (OA). We compared genotype frequencies of the MATN-1 gene (1p35) in patients with OA and controls to determine if there is any association between the MATN-1 genotype and OA. METHODS: 73 OA patients and 53 controls from a rheumatology ambulatory center and a university hospital were studied. They were unrelated subjects. Controls were free of clinical OA. OA was defined according to the American College of Rheumatology criteria. The MATN-1 microsatellite in the 3'untranslated region was amplified by PCR. The size of the amplification products was determined by capilar electrophoresis in a DNA Genetic Analizer Genotypic distribution was compared by the chi2 test. RESULTS: We identified 4 alleles according to their basepair (bp) length: A1 = 110 bp; A2 = 108 bp; A3 = 106 bp and A6 = 104 pb. Six genotypes were found, with an observed heterozygosity of 0.48. The most frequent genotype in OA and controls was A1/A1 (43.8% and 43.4%, respectively). No significant difference in genotype distribution was found between OA - even when discriminating by the affected joint - and controls. CONCLUSION: We did not find any difference in the MATN-1 genotype distribution in OA patients and controls. To our knowledge, this would be the first time a MATN-1 allele of 104 bp (A6) has been identified These results do not support a role of the MATN-1 genotypes in the occurrence of clinical OA.

A randomized trial of the efficacy and tolerability of the COX-2 inhibitor rofecoxib vs ibuprofen in patients with osteoarthritis. Rofecoxib/Ibuprofen Comparator Study Group.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). It is not known whether a specific inhibitor of COX-2 will provide efficacy in osteoarthritis (OA) comparable with NSAIDs. Therefore, we compared the efficacy and safety of the rofecoxib, which specifically inhibits COX-2, with those of the NSAID ibuprofen in patients with OA. OBJECTIVE: To compare the clinical efficacy and tolerability of rofecoxib (12.5 and 25 mg once daily) with ibuprofen (800 mg 3 times daily). METHODS: A randomized, double-blind trial of 809 adults with OA was conducted. Patients with OA in whom the knee or hip was the primary source of pain were randomized to 1 of 4 treatment groups on demonstration of disease activity: placebo; rofecoxib, 12.5 or 25 mg once daily; or ibuprofen, 800 mg 3 times daily. Clinical efficacy and safety were monitored during a 6-week treatment period. RESULTS: Both doses of rofecoxib demonstrated efficacy clinically comparable with ibuprofen as assessed by 3 primary end points (pain walking on a flat surface [Western Ontario and McMaster Universities Osteoarthritis Index], patient global assessment of response to therapy, and investigator global assessment of disease status) according to predefined comparability criteria. Both rofecoxib doses and the ibuprofen dose provided significantly (P<.001) greater efficacy than placebo on all primary end points. Results from secondary end points were consistent with those of the primary end points. All treatments were well tolerated; the overall incidence rates of clinical adverse experiences were not significantly different (P>.05) among the treatment groups. CONCLUSION: Rofecoxib was well tolerated and provided clinical efficacy comparable with a high dose of the NSAID ibuprofen.

[Collagenase production increases in rheumatoid arthritis and osteoarthritis synoviocytes incubated]. / Incremento en la produccion de colagenasa en incubado de sinoviocitos de pacientes con artritis reumatoidea y osteoartrosis.

Cartilage is a specialized connective tissue. It contains few cells into an extracell matrix. The matrix mainly constituents are collagen and proteoglycans. Its degradation depends on synoviocytes activity, that secrete metalloproteases, agents to proteoglycans catabolism. There are two types of synoviocytes: macrophagics (type "A:') and fibroblastics (type "B"). The proteoglycan destruction can be LT-dependent or LT-independent. The aim of this work is synoviocytes function ex vívo study, free immune system influence. In order to do it, heparinized synovial fluid samples were obtained from 6 osteoarthritic (OA) and 6 arthritic (RA) both sex untreated patients, diagnosed according ACR criteria, which disease duration was longer than 6 months. Patients average age was 70 +/- 2 years. Control samples were synovial fluid from traumatic arthritis or non inflammatory bone-muscle pathology. Synovial fluid was centifugated at 1500 g for 30 minutes to isolate synoviocytes. Sediment containing cells was 6 hs incubed with Dulbecco-Eagles media, that has HEPES Gibco (26 mM); NaHCO3 (0.5 g/I); glutamine (2 mM), streptomicine (100 mg/l), G-penicillin (1 U/ml); anphotericine B (2.5 mg/l). Cells calification and viability were cytopathologically determined. Before and after incubation, collagenase activity was measured by ELISA-double-sandwich, using 10 micrograms/ml monoclonal anti-MMPs in phosphate-buffer-saline. The antigen-antibody complex production with inespecific proteins was blocked by bovine seric albumine. Streptavidin peroxidase was added and washed with 2,2,azin,di(3-ethyl-benztazoilinsuiphonic) acid to develop color. The link of labeled antibody by absorbance at 410 nm was determined in ELISA-spectrophothometer. RA patients earlier MMPs synoviocytes production was 1373 +/- 115 ng/ml. Then 6 hs incubation 2143 +/- 132 ng/ml was reached. The increase (56%) had high significance (p < 0.0001). OA earlier MMPs cells production was 276 +/- 23 ng/ml, but after incubation it reached 542 +/- 47 ng/ml. (96% increased with highly significativa difference too: p < 0.0001). Microscopic study was carried out before and after incubation, and shows a lot of synoviocytes with plenty of cytopiasme when the collagenase leveis were highest. On the contrary, when low MMPs production by synovial fluid, as no incubated osteoarthritic material, a few cells containing picnotics nucleous were observed. Significant quantitative differences in AR and OA enzymatic secretion were observed. Although in rheumatoid arthritic MMPs leveis synoviocytes production were 4.6 times than OA levels, after 6 hs incubation percentage of increase in OA cells secretion was highest. Described results confirm MMP-1 synthesis by synoviocytes, and these levels correlate with inflammation, more pronounced in acute (RA) than chronic pathology (OA). Synoviocyte incubation let us to test disease changes in synovial fluid according to cells number and phagocytic activity. Authors agree to assert that synovial fluid may reflect what is happening in an articular cartilago, because SF provides markers of joint disease. MMPs are giving information about pathways involved in OA and RA cartilage degradation.

Incremento en la produccion de colagenasa en incubado de sinoviocitos de pacientes con artritis reumatoidea y osteoartrosis. / [Collagenase production increases in rheumatoid arthritis and osteoarthritis synoviocytes incubated]

Cartilage is a specialized connective tissue. It contains few cells into an extracell matrix. The matrix mainly constituents are collagen and proteoglycans. Its degradation depends on synoviocytes activity, that secrete metalloproteases, agents to proteoglycans catabolism. There are two types of synoviocytes: macrophagics (type [quot ]A:) and fibroblastics (type [quot ]B[quot ]). The proteoglycan destruction can be LT-dependent or LT-independent. The aim of this work is synoviocytes function ex vívo study, free immune system influence. In order to do it, heparinized synovial fluid samples were obtained from 6 osteoarthritic (OA) and 6 arthritic (RA) both sex untreated patients, diagnosed according ACR criteria, which disease duration was longer than 6 months. Patients average age was 70 +/- 2 years. Control samples were synovial fluid from traumatic arthritis or non inflammatory bone-muscle pathology. Synovial fluid was centifugated at 1500 g for 30 minutes to isolate synoviocytes. Sediment containing cells was 6 hs incubed with Dulbecco-Eagles media, that has HEPES Gibco (26 mM); NaHCO3 (0.5 g/I); glutamine (2 mM), streptomicine (100 mg/l), G-penicillin (1 U/ml); anphotericine B (2.5 mg/l). Cells calification and viability were cytopathologically determined. Before and after incubation, collagenase activity was measured by ELISA-double-sandwich, using 10 micrograms/ml monoclonal anti-MMPs in phosphate-buffer-saline. The antigen-antibody complex production with inespecific proteins was blocked by bovine seric albumine. Streptavidin peroxidase was added and washed with 2,2,azin,di(3-ethyl-benztazoilinsuiphonic) acid to develop color. The link of labeled antibody by absorbance at 410 nm was determined in ELISA-spectrophothometer. RA patients earlier MMPs synoviocytes production was 1373 +/- 115 ng/ml. Then 6 hs incubation 2143 +/- 132 ng/ml was reached. The increase (56

) had high significance (p < 0.0001). OA earlier MMPs cells production was 276 +/- 23 ng/ml, but after incubation it reached 542 +/- 47 ng/ml. (96

increased with highly significativa difference too: p < 0.0001). Microscopic study was carried out before and after incubation, and shows a lot of synoviocytes with plenty of cytopiasme when the collagenase leveis were highest. On the contrary, when low MMPs production by synovial fluid, as no incubated osteoarthritic material, a few cells containing picnotics nucleous were observed. Significant quantitative differences in AR and OA enzymatic secretion were observed. Although in rheumatoid arthritic MMPs leveis synoviocytes production were 4.6 times than OA levels, after 6 hs incubation percentage of increase in OA cells secretion was highest. Described results confirm MMP-1 synthesis by synoviocytes, and these levels correlate with inflammation, more pronounced in acute (RA) than chronic pathology (OA). Synoviocyte incubation let us to test disease changes in synovial fluid according to cells number and phagocytic activity. Authors agree to assert that synovial fluid may reflect what is happening in an articular cartilago, because SF provides markers of joint disease. MMPs are giving information about pathways involved in OA and RA cartilage degradation.

Proteoglycan's activation by adhesion molecules and L metalloproteases in rheumatoid arthritis and osteoarthritis.

Two groups of patients were studied, both in accordance with ACR criteria. First group (41 cases) suffering R.A. Second group (36 cases) suffering O.A. In both pathologies MMPs, ICAM and VCAM from synovial fluid and plasma were studied. Measurements were made with ELISA-sandwich in a Metrolab spectrophotometer at 410 nm for MMPs, and 491 nm for ICAM and VCAM. As control, samples of patients with noninflammatory muscle skeletal disorders or traumatic arthritis and healthy witness were used. Synovial concentration of MMPs in R.A. was 1402 +/- 76 ng/ml, a higher significant value (p < 0.0001) compared with osteoarthritis: 353 +/- 23 ng/ml. In the witness plasma, MMPs were not detected. Plasmatic and synovial levels of the adhesion molecules present different values in both pathologies and between them. Synovial ICAM level in R.A. (280 +/- 9.8 ng/ml) is significantly higher than in O.A. (163 +/- 10 ng/ml) (p < 0.001), but lower than the plasmatic ones (370 +/- 35 ng/ml) (p < 0.001). All these values are significantly higher than the normal plasma (121 +/- 6.5 ng/ml) (p < 0.01, p < 0.005, and p < 0.0001, respectively) VCAM increase regarding basal values (140 +/- 5.6 ng/ml) (p < 0.001) and in a similar proportion for both pathologies (R.A.: 186 +/- 9.3 ng/ml and O.A.: 207 +/- 14.3 ng/ml). Their plasmatic levels were higher (270 +/- 45 and 320 +/- 38 ng/ml) (p < 0.001) but without significative difference between them. There is correlation among MMPs, ICAM and VCAM variations. The variability can be explained by concomitance several evolutive steps. Each pathology shows a different grade of cellularity, inverted predominance in the relation TIMPs/ collagenase and different generator mechanisms of MMPs. Our findings reinforce the importance as diagnostic guide of adhesion molecules dosage, and possible therapeutic use of MMPs inhibitors and ICAM or VCAM antagonists en R.A. and related pathologies.

Proteoglycan's activation by adhesion molecules and L metalloproteases in rheumathoid arthritis and ostheoarthritis

Two groups of patients were studied, both in accordance with ACR criteria. First group (41 cases) suffering R.A.. Second group (36 cases) suffering O.A. In both pathologies MMPs, ICAM and VCAM from synovial fluid and plasma were studied. Measurements were made with ELISA-sandwich in a Metrolab spectrophotometer at 410 mm for MMPs, and 491 nm for ICAM and VCAM. As control, samples of patients with noninflammatory muscle skeletal disorders or traumatic arthritis and healthy witness were used. Synovial concentration of MMPs in R.A. was 1402+76 ng/ml, a higher significant value (p<0.0001) compared with ostheoarthritis: 353+23 ng/ml. In the witness plasma, MMPs were not detected. Plasmatic and synovial levels of the adhesion molecules present different values in both pathologies and between them. Synovial ICAM level in R.A. (280+9.8 ng/ml) is significantly higher than in O.A. (163+10 ng/ml) (p<0.001), but lower than plasmatic ones (370+35 ng/ml) (p,0.001). All these values are significantly higher than the normal plasma (121+6.5 ng/ml) (p<0.005, and p<0.0001, respectively) VCAM increase regarding basal values (140+5.6 ng/ml) (p<0.001) and in a similar proportion for both pathologies (R.A.: 186+9.3 ng/ml and O.A.: 207+14.3 ng/ml). Their plasmatic levels were higher (270+45 and 320+38 ng/ml) (p<0.001) but without significative difference between them. There is correlation among MMPs, ICAM and VCAM variations. The variability can be explained by concomitance several evolutive steps. Each pathology shows a different grade of cellularity, inverted predominance in the relation TIMPs/collagenase and different generator mechanisms of MMPs. Our findings reinforce the importance as diagnostic guide of adhesion molecules dosage, and possible therapeutic use of MMPs inhibitors and ICAM ou VCAM antagonists en R.A. and related pathologies.

Proteoglycans activation by adhesion molecules and L metalloproteases in rheumathoid arthritis and ostheoarthritis

Two groups of patients were studied, both in accordance with ACR criteria. First group (41 cases) suffering R.A.. Second group (36 cases) suffering O.A. In both pathologies MMPs, ICAM and VCAM from synovial fluid and plasma were studied. Measurements were made with ELISA-sandwich in a Metrolab spectrophotometer at 410 mm for MMPs, and 491 nm for ICAM and VCAM. As control, samples of patients with noninflammatory muscle skeletal disorders or traumatic arthritis and healthy witness were used. Synovial concentration of MMPs in R.A. was 1402+76 ng/ml, a higher significant value (p<0.0001) compared with ostheoarthritis: 353+23 ng/ml. In the witness plasma, MMPs were not detected. Plasmatic and synovial levels of the adhesion molecules present different values in both pathologies and between them. Synovial ICAM level in R.A. (280+9.8 ng/ml) is significantly higher than in O.A. (163+10 ng/ml) (p<0.001), but lower than plasmatic ones (370+35 ng/ml) (p,0.001). All these values are significantly higher than the normal plasma (121+6.5 ng/ml) (p<0.005, and p<0.0001, respectively) VCAM increase regarding basal values (140+5.6 ng/ml) (p<0.001) and in a similar proportion for both pathologies (R.A.: 186+9.3 ng/ml and O.A.: 207+14.3 ng/ml). Their plasmatic levels were higher (270+45 and 320+38 ng/ml) (p<0.001) but without significative difference between them. There is correlation among MMPs, ICAM and VCAM variations. The variability can be explained by concomitance several evolutive steps. Each pathology shows a different grade of cellularity, inverted predominance in the relation TIMPs/collagenase and different generator mechanisms of MMPs. Our findings reinforce the importance as diagnostic guide of adhesion molecules dosage, and possible therapeutic use of MMPs inhibitors and ICAM ou VCAM antagonists en R.A. and related pathologies. (AU)

[The percutaneous absorption of diclofenac]. / Die perkutane Resorption von Diclofenac.

The percutaneous absorption of diclofenac diethylammonium 1.16% (w/w) in a combination of emulsion cream and gel (Voltaren Emulgel) and of diclofenac sodium 1% (w/w) in a cream formulation (Voltaren cream) was investigated in guinea-pig, rabbit and man. The percutaneous absorption of diclofenac sodium in guinea-pig was 3 to 6% of the dose when the cream formulation in doses of 320, 100 or 40 mg was applied on 10 cm2 of occluded skin and left in place for 6 h. The transdermal delivery of 14C-labelled diclofenac yielded plateau plasma concentrations of radiotracer from 1.5 h after application until removal of the residual cream. Subsequently the steady state drug depots in the skin and muscle tissue were depleted promptly. During daily administration the steady state levels in the muscle tissue in proximity to the application site were about 3 times higher than in distant muscle tissue. By topical application on knee joints of rabbits diclofenac penetrated into the patellar ligament, the adipose corpus and the synovial fluid. In man the percutaneous absorption was 6% of the dose when the Emulgel formulation was spread by 5 mg/cm2 and left for 12 h on non-occluded skin. The pattern of metabolites of diclofenac in human urine was the same after topical and oral administration. In man, upon daily topical administration of 3 times 2.5 g cream formulation (10 mg/cm2) the diclofenac steady state plasma levels were 20 to 40 nmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Farmacodinamia clínica del ácido tiaprofénico / Clinical pharmacodynamics of the tiaprofenic acid

El ácido tiaprofénico [ácido alfa-benzoil-5-thienil- 2 propiónico ha demostrado ser un activo inhibidor reversible de la ciclooxigenasa. La evidencia de que ciertas prostaglandinas (PGs), enzimas lisozómicas y otros autacoides producían injuria articular y reacciones sinoviales, nos sugirió la investigación de la eficacia a corto plazo del ácido tiaprofénico, en el tratamiento de la artritis reumatoidea. El estudio fue realizado sobre 20 pacientes adultos, portadores de sinovitis con derrame, a los cuales fue suspendida toda otra medicación antiinflamatoria, 7 días antes de comenzar el estudio. En todos los pacientes se analizó la concentración de: PGE2 2, P6F2-alfa fosfatasa ácida, dehidrogenasa láctica y cantidad de células en el líquido sinovial, antes y después de 8 días de tratamiento con 600mg/día/vía oral, de ácido tiaprofénico. La detección de los niveles de las PGs se realizó por cromatografía sobre capa fina y ensayo biológico sobre fundus gástrico de rata, contra testigo. Luego del 5º día se observó una disminución progresiva de la reacción inflamatoria. En corto tiempo el ácido tiaprofénico provocó una caída significativa en los valores de LDH (p<0,02), PGE2 (p<0,001), fosfatasa ácida (p<0,005)., PGF2-alfa (p<0,001) y en el número de células (p<0,02). Concluimos en que el ácido tiaprofénico es una droga anti-PGs y antiinflamatoria efectiva a corto período de tratamiento (AU)

Farmacodinamia clínica del ácido tiaprofénico / Clinical pharmacodynamics of the tiaprofenic acid

El ácido tiaprofénico [ácido alfa-benzoil-5-thienil- 2 propiónico ha demostrado ser un activo inhibidor reversible de la ciclooxigenasa. La evidencia de que ciertas prostaglandinas (PGs), enzimas lisozómicas y otros autacoides producían injuria articular y reacciones sinoviales, nos sugirió la investigación de la eficacia a corto plazo del ácido tiaprofénico, en el tratamiento de la artritis reumatoidea. El estudio fue realizado sobre 20 pacientes adultos, portadores de sinovitis con derrame, a los cuales fue suspendida toda otra medicación antiinflamatoria, 7 días antes de comenzar el estudio. En todos los pacientes se analizó la concentración de: PGE2 2, P6F2-alfa fosfatasa ácida, dehidrogenasa láctica y cantidad de células en el líquido sinovial, antes y después de 8 días de tratamiento con 600mg/día/vía oral, de ácido tiaprofénico. La detección de los niveles de las PGs se realizó por cromatografía sobre capa fina y ensayo biológico sobre fundus gástrico de rata, contra testigo. Luego del 5§ día se observó una disminución progresiva de la reacción inflamatoria. En corto tiempo el ácido tiaprofénico provocó una caída significativa en los valores de LDH (p<0,02), PGE2 (p<0,001), fosfatasa ácida (p<0,005)., PGF2-alfa (p<0,001) y en el número de células (p<0,02). Concluimos en que el ácido tiaprofénico es una droga anti-PGs y antiinflamatoria efectiva a corto período de tratamiento

Anti-prostaglandin and anti-inflammatory short-term efficacy of piroxicam in rheumatoid arthritis.

The efficacy of anti-inflammatory agents is related to their concentration in the peripheral compartments. In rheumatoid arthritis a drug's affinity for synovial tissue and synovial fluid is a decisive factor in treatment. The short-term efficacy of piroxicam was studied, relating the synovial concentration of prostaglandins and acid phosphatase and LDH to piroxicam synovial and plasma levels. After withdrawal of synovial fluid for pre-treatment measurements, 10 patients received 20 to 30 mg of piroxicam/day for eight days. The drug reached an average level of 3.56 +/- 0.9 micrograms/ml in synovial fluid, and 7.73 +/- 1.6 micrograms/ml in plasma. The acid phosphatase decreased from an initial average level of 29 mu/ml to a final average level of 15.999 mu/ml. The LDH showed an initial average level of 725.3 mu/ml and a final average of 471.2 mu/ml (p less than 0.01). The prostaglandin levels were quantified by two methods: indirectly, by measuring the malonilaldehyde concentration in nMol/ml, which showed an average level decrease of 48.75% in 100% of the cases; and directly, by means of thin layer chromatography and biological assay on rats' gastric fundus, against controls. The disappearance of PGE1 and a significant decrease in PGF2 alpha (100%) were observed. We conclude that piroxicam is an effective drug for the short-term treatment of rheumatoid arthritis. It penetrates rheumatoid synovial fluid, reaching 50% plasma concentrations. It has an anti-prostaglandin action, and could stabilize lysosomal membrane.

A simple method for detection of IgG rheumatoid factor.

A simple method for detection of IgG rheumatoid factor (RF) in sera and joint fluid is described. The technique is based on the action of 0.1 M 2-mercaptoethanol mixed directly with the material. After 2 h of incubation determinations of human anti-IgG were performed by latex agglutination test. Comparison with data obtained by using the conventional method, sequential 24 h treatment with 0.1 M 2-mercaptoethanol and 0.01 M iodoacetamide, shows similar results for both methods. A correlation was observed between the presence of IgGRF in synovial fluid and a severe clinical course with invalidating forms in patients suffering rheumatoid arthritis.