RESUMEN
The key to successful treatment of acute bacterial arthritis is early diagnosis and initiation of empirical antibacterial therapy. Treatment includes antimicrobial therapy, debridement of the infected joint and treatment of pain. Empirical antibacterial treatment should be re-evaluated as soon as the causative pathogen is identified from joint fluid and other cultures. Mobilisation with partial weight bearing is encouraged early during treatment. The outcome of properly treated bacterial arthritis in the elderly is generally favourable and at least 50% of patients may recover without developing secondary osteoarthritis.
Asunto(s)
Artritis Infecciosa , Anciano , Antibacterianos/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Artralgia/tratamiento farmacológico , Artritis Infecciosa/diagnóstico , Artritis Infecciosa/tratamiento farmacológico , Artritis Infecciosa/cirugía , HumanosRESUMEN
Gastrointestinal absorption of bisphosphonates is highly variable from individual to individual (between-subject variation) and from day to day (within-subject variation), a fact that creates problems both in research and in clinical use of these drugs. We conducted a randomized, two-period cross-over pharmacokinetic (phase I) study to assess the relative bioavailability of two different clodronate preparations: an 800 mg tablet and a 400 mg capsule. Urinary excretion of clodronate correlates with gastrointestinal absorption. To minimize the confounding effect of the high variability of gastrointestinal absorption, we chose as the primary parameter the cumulative amount of clodronate excreted into urine (A(e0-t)) during 9 days (7 days of treatment, 2 days of follow-up). The 90% confidence interval calculated for the population medians of A(e0-t) was 0.83-1.09, well within the 90% confidence interval stipulated for bioequivalence for the area under the curve values (0.80-1.25). This new procedure for pooling urinary excretion data offered a clear advantage over previous methods, and thus could presumably be used to study other drugs as well that are not metabolized and may show highly variable gastrointestinal absorption.
Asunto(s)
Analgésicos no Narcóticos/farmacocinética , Ácido Clodrónico/farmacocinética , Administración Oral , Adolescente , Adulto , Analgésicos no Narcóticos/administración & dosificación , Analgésicos no Narcóticos/farmacología , Analgésicos no Narcóticos/orina , Análisis de Varianza , Área Bajo la Curva , Disponibilidad Biológica , Cápsulas/metabolismo , Cápsulas/normas , Ácido Clodrónico/administración & dosificación , Ácido Clodrónico/farmacología , Ácido Clodrónico/orina , Estudios Cruzados , Femenino , Estudios de Seguimiento , Semivida , Humanos , Absorción Intestinal/efectos de los fármacos , Absorción Intestinal/fisiología , Masculino , Estándares de Referencia , Reproducibilidad de los Resultados , Programas Informáticos , Comprimidos/metabolismo , Comprimidos/normas , Equivalencia TerapéuticaRESUMEN
OBJECTIVES: To investigate the role of complement cascade induced damage and protection against it in acute arthritides compared to rheumatoid arthritis and other chronic joint derangements. METHODS: C3c, C9, and protectin (CD59) were examined by avidin-biotin-peroxidase complex staining. RESULTS: Marked deposits of C3c and C9 were found in synovial vasculature and intercellular matrix of the lining in rheumatoid arthritis and in acute arthritides (including bacterial, reactive, and osteoarthritis flare up). Furthermore, protectin was not visible in synovial lining cells and was relatively weakly expressed in stromal and endothelial cells in rheumatoid arthritis; also in acute arthritides protectin expression was weak. In contrast, C3c and C9 deposits were not found in chronic conditions associated with degenerative diseases (osteoarthritis and osteochondritis dissecans) or mechanical causes (patellar luxation and a ruptured meniscus), in which also the protectin expression was prominent in synovial lining, endothelial and some stromal cells. CONCLUSIONS: Activation of the complement in rheumatoid arthritis and in acute arthritides seems to be associated with a decreased protection of synovial cells against cellular effects and lysis mediated by membrane attack complex.
Asunto(s)
Artritis/inmunología , Proteínas del Sistema Complemento/análisis , Membrana Sinovial/inmunología , Enfermedad Aguda , Adulto , Anciano , Anciano de 80 o más Años , Artritis Reumatoide/inmunología , Antígenos CD59/análisis , Enfermedad Crónica , Complemento C3c/análisis , Complemento C9/análisis , Complejo de Ataque a Membrana del Sistema Complemento/análisis , Femenino , Humanos , Traumatismos de la Rodilla/inmunología , Masculino , Persona de Mediana Edad , Osteoartritis/inmunología , Osteocondritis Disecante/inmunología , Sinovitis/inmunologíaRESUMEN
Based on the fact that synovial lining cells have some properties of transformed-appearing cells, we have examined the expression of Myc, Myb, Fos, Jun and Ras oncoproteins in synovial tissues from patients with different types of arthritis. Formalin-fixed and paraffin-embedded sections of synovial tissue from 12 patients with rheumatoid arthritis (RA), 14 with reactive arthritis (ReA), nine with other seronegative arthritis (OSA), seven with bacterial arthritis (BA), eight with probable bacterial arthritis (PBA) and eight with osteoarthritis (OA) were studied using the immunoperoxidase staining technique. The oncoproteins studied were expressed both in the synovial lining layer and in the sublining layer, consisting of lymphocytes, other inflammatory cells and blood vessels. Among the six disease entities, RA and OA appeared to be the most distinct, whereas the results obtained for ReA and OSA, and on the other hand for BA and PBA, closely resembled each other. The expression of Myc, Myb, Fos and Jun was significantly correlated both to the degree of synovial hypercellularity and the synovial lymphocytic infiltration. For Ras, such a correlation could not be seen. We conclude that we find no evidence of a cell lineage-specific or a disease-specific abnormality of proto-oncogene products in RA, and the expression of these oncoproteins is consistent with inflammation rather than with any primary abnormality of cell growth.
Asunto(s)
Artritis/diagnóstico , Proteínas Oncogénicas/biosíntesis , Membrana Sinovial/química , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Aminoácidos , Especificidad de Anticuerpos , Artritis/metabolismo , Artritis Infecciosa/metabolismo , Artritis Reactiva/metabolismo , Artritis Reumatoide/metabolismo , Proteínas de Unión al ADN/análisis , Proteínas de Unión al ADN/biosíntesis , Proteínas de Unión al ADN/inmunología , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Proteínas Oncogénicas/análisis , Proteínas Oncogénicas/inmunología , Osteoartritis/metabolismo , Prohibitinas , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas/análisis , Proteínas Proto-Oncogénicas/biosíntesis , Proteínas Proto-Oncogénicas/inmunología , Proteínas Proto-Oncogénicas c-fos/análisis , Proteínas Proto-Oncogénicas c-fos/biosíntesis , Proteínas Proto-Oncogénicas c-fos/inmunología , Proteínas Proto-Oncogénicas c-jun/análisis , Proteínas Proto-Oncogénicas c-jun/biosíntesis , Proteínas Proto-Oncogénicas c-jun/inmunología , Proteínas Proto-Oncogénicas c-myb , Proteínas Proto-Oncogénicas c-myc/análisis , Proteínas Proto-Oncogénicas c-myc/biosíntesis , Proteínas Proto-Oncogénicas c-myc/inmunología , Transactivadores/análisis , Transactivadores/biosíntesis , Transactivadores/inmunología , Proteínas ras/análisis , Proteínas ras/biosíntesis , Proteínas ras/inmunologíaRESUMEN
Estramustine phosphate is generally used as a second-line treatment in patients with advanced prostate cancer. The bone metastases due to the cancer are often treated simultaneously with clodronate in order to relieve the bone pain. Therefore, the interaction of clodronate (800 mg orally four times daily) and estramustine phosphate (280 mg orally twice daily) on their bioavailability was studied in twelve patients with prostate carcinoma and bone metastases. The drugs were first given separately, each to six patients, for five days, and then concomitantly for the same period. The bioavailabilities of the drugs were calculated on the last day of each treatment period. When clodronate was given alone, its concentrations in serum and AUC for one dose interval (6 hr) did not differ from those obtained with the drug given concomitantly with estramustine phosphate, nor did the combination of estramustine phosphate change the excretion of clodronate in urine. The serum concentrations of estramustine phosphate were elevated by about 80% when the drug was given together with clodronate. The AUC for one dose interval (12 hr) was also significantly higher for estramustine phosphate with clodronate than without clodronate. The urinary excretion of estrone, a major metabolite of estramustine phosphate, was also significantly higher after the admission with clodronate. The results suggest that clodronate increases the oral bioavailability of estramustine phosphate.
Asunto(s)
Analgésicos no Narcóticos/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , Ácido Clodrónico/uso terapéutico , Estramustina/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Administración Oral , Anciano , Anciano de 80 o más Años , Analgésicos no Narcóticos/administración & dosificación , Analgésicos no Narcóticos/farmacocinética , Análisis de Varianza , Antineoplásicos Hormonales/administración & dosificación , Antineoplásicos Hormonales/farmacocinética , Disponibilidad Biológica , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/secundario , Carcinoma/tratamiento farmacológico , Ácido Clodrónico/administración & dosificación , Ácido Clodrónico/farmacocinética , Ácido Clodrónico/orina , Sinergismo Farmacológico , Quimioterapia Combinada , Estramustina/administración & dosificación , Estramustina/farmacocinética , Estramustina/orina , Cromatografía de Gases y Espectrometría de Masas , Humanos , Masculino , Persona de Mediana Edad , Dolor/tratamiento farmacológicoRESUMEN
OBJECTIVE: The effect of food on the bioavailability of oxybutynin was assessed in a randomised cross-over study in 23 healthy volunteers. A single oral 10 mg dose of a controlled release oxybutynin tablet was administered after a high fat breakfast and to fasting subjects. The AUC, Cmax, tmax, t1/2 and MRT of oxybutynin and its active metabolite N-desethyloxybutynin were determined. RESULTS: Breakfast did not change the AUC of oxybutynin but increased the AUC of N-desethyloxybutynin by about 20%. The Cmax of oxybutynin and N-desethyloxybutynin were two-fold higher when the drug was administered after breakfast compared to the fasting state. CONCLUSION: Breakfast significantly reduced the MRT of oxybutynin and N-desethyloxybutynin.
Asunto(s)
Antagonistas Colinérgicos/farmacocinética , Interacciones Alimento-Droga , Alimentos , Ácidos Mandélicos/farmacocinética , Adulto , Área Bajo la Curva , Disponibilidad Biológica , Estudios Cruzados , Preparaciones de Acción Retardada , Femenino , Semivida , Humanos , MasculinoRESUMEN
Determination of synovial fluid (SF) lactic acid has been suggested to be an unspecific indicator of SF leukocytosis, and it is not recommended for differential diagnosis of bacterial arthritis. We analyzed the L-lactic acid content by enzymatic UV-method in 65 SF samples obtained from adult patients with acute knee arthritides. The concentration of L-lactic acid was not high in any SFs with intensive leukocytosis. The mean concentration of L-lactic acid was 13.5 mmol/l (95% confidence intervals 9.4; 17.6 mmol/l) in the synovial-fluid samples from culture-positive arthritis and 5.5 mmol/l (4.9; 6.2 mmol/l) in the synovial-fluid samples from culture-negative arthritis. Determination of SF L-lactic acid is an important part of the diagnostic setup for acute arthritis. Values > 9 mmol/l strongly support occurrence of bacterial arthritis and indicates an immediate onset of the treatment.
Asunto(s)
Artritis/metabolismo , Articulación de la Rodilla/metabolismo , Lactatos/metabolismo , Líquido Sinovial/metabolismo , Enfermedad Aguda , Adolescente , Adulto , Anciano , Artritis Infecciosa/metabolismo , Artritis Infecciosa/microbiología , Infecciones Bacterianas/metabolismo , Infecciones Bacterianas/microbiología , Femenino , Humanos , Ácido Láctico , Masculino , Persona de Mediana Edad , Concentración Osmolar , Estudios Prospectivos , Líquido Sinovial/microbiologíaRESUMEN
The use of blood culture methods for culture of synovial fluid (SF) has been suggested to increase the yield of microbes from SF of patients with septic arthritis. We report on a study of 94 SF cultures of 90 adult patients with acute effusions of the knee joint. Three different culture methods were used: conventional agar plate culture, culture with lysis and centrifugation (Isolator) and broth enrichment (BACTEC 6A and 7A). Blood was cultured simultaneously from 76 patients. In the patients with clinical septic arthritis, the SF cultures were positive by all the methods in 8 patients and negative by all the methods in 19 patients. The contamination rate of the SF cultures was 3/215 in the patients without clinical septic arthritis. We conclude that reliable evidence of septic arthritis is emerged from a SF culture by a single method, and that the choice of culture method is less critical. In addition, we discuss the role of blood cultures in the diagnosis of acute arthritides.
Asunto(s)
Artritis Infecciosa/microbiología , Líquido Sinovial/microbiología , Enfermedad Aguda , Adulto , Técnicas Bacteriológicas , Sangre , Medios de Cultivo , Humanos , Salmonella/aislamiento & purificación , Yersinia/aislamiento & purificaciónRESUMEN
Presence of muramic acid, a bacterial cell wall component, was analysed by gas chromatography-mass spectrometry in synovial fluid (SF) of 40 patients with acute inflammatory arthritis. SF muramic acid was observed in 4/14 patients with acute, culture negative inflammatory arthritis of unclear origin. Each of these four patients had a history of a recent bacterial disease (pansinuitis, purulent leg ulcer, erysipelas, unexplained fever with suspicion of cholecystitis and urinary tract infection). In the bacterial arthritis, SF muramic acid was detected in 6/12 patients (in 2/6 culture negative cases). In the reactive arthritis due to Salmonella or Yersinia, the rate of positivity was 2/14. Nineteen samples of traumatic SF effusion were muramic acid negative. These findings indicate that several cases of undefined acute inflammatory arthritis are of bacterial origin.
Asunto(s)
Artritis Reactiva/metabolismo , Ácidos Murámicos/análisis , Infecciones por Salmonella/metabolismo , Líquido Sinovial/química , Yersinia/metabolismo , Enfermedad Aguda , Cromatografía de Gases y Espectrometría de Masas , Humanos , Ácidos Murámicos/metabolismoRESUMEN
The pharmacokinetic parameters describing the fate of one intravenous clodronate (disodium dichloromethane diphosphonate) dose was studied in 24 normal subjects and in 24 patients with different degrees of renal insufficiency. The aim of the study was to derive data for adjustment of dosage in relation to renal function. Disodium clodronate in serum and urine samples was analyzed by capillary gas chromatography with mass-selective detection. The renal clearance (CLR) of clodronate was highly dependent on renal function and declined successively with declining glomerular filtration rate (GFR). Plasma clearance (CLP) declined, too, but to a lesser degree than CLR. The impairment of renal function resulted in decreased cumulative urinary elimination of clodronate and increased total areas under the serum concentration-time curve (AUC0-infinity). Hence, as the renal elimination of clodronate diminishes with decreasing GFR, there is a related retention of the substance. As a result of the present study, the following dosages are recommended: creatinine clearance (CLCr) from 50 to 80 ml/minute, 75-100% of normal dose; CLCr 12-50 ml/minute, 50-75% of normal dose; and ClCr < 12 ml/minute, 50% of normal dose. The results must be interpreted with caution in patients with malignancy and severe skeletal disease, in whom the nonrenal clearance may vary markedly.
Asunto(s)
Ácido Clodrónico/farmacocinética , Adulto , Anciano , Ácido Clodrónico/administración & dosificación , Ácido Clodrónico/sangre , Ácido Clodrónico/orina , Femenino , Semivida , Humanos , Infusiones Intravenosas , Fallo Renal Crónico/metabolismo , Masculino , Tasa de Depuración Metabólica , Persona de Mediana Edad , Factores de TiempoRESUMEN
Increased catalytic activity of synovial-type (group II) phospholipase A2 (syn-PLA2), has been associated with cartilage erosions in rheumatoid arthritis and osteoarthritis. The catalytic activity of phospholipase A2 and the concentration of syn-PLA2 were measured in a prospective study in synovial fluid (SF) samples from 66 patients with acute knee joint effusion. The median (range) of the concentration of syn-PLA2 in SF was 210 micrograms/l (80-1480 micrograms/l) in culture-positive septic arthritis, 460 micrograms/l (270-1040 micrograms/l) in reactive arthritis, 780 micrograms/l (120-2710 micrograms/l) in osteoarthritis and 230 micrograms/l (80-1400 micrograms/l) in traumatic joint effusions. High concentrations of syn-PLA2 are found also in SF of patients with arthritides not expected to lead to permanent destruction of cartilage.
Asunto(s)
Artritis/metabolismo , Fosfolipasas A/metabolismo , Líquido Sinovial/metabolismo , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Catálisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Concentración Osmolar , Fosfolipasas A/sangre , Fosfolipasas A2RESUMEN
The use of D-lactic acid in differential diagnosis of bacterial arthritis was evaluated in a prospective study. The concentration of D-lactic acid was determined by the enzymatic UV-method in sixty-eight synovial fluids (SF) and in twenty four sera from adult patients with acute knee effusion. High concentrations of D-lactic acid (> 0.15 mmol/l) were measured most frequently in SF from bacterial arthritis, but also in individual culture-negative SF samples from patients with inflammatory culture-negative joint effusions with and without identified history of infections. Determination of SF D-lactic acid is not useful in differential diagnosis of bacterial arthritis.
Asunto(s)
Artritis Infecciosa , Lactatos/análisis , Líquido Sinovial/química , Artritis Infecciosa/sangre , Diagnóstico Diferencial , Humanos , Lactatos/sangre , Ácido Láctico , Estudios ProspectivosRESUMEN
In this comparative analysis of laboratory data, we examined the characteristics of synovial fluid leukocytosis in eighty adult patients with bacterial arthritis, reactive arthritis or rheumatoid arthritis of the knee joint. Synovial fluid leukocyte count and the percentage of polymorphonuclear cells seemed to perform well as a discriminator between bacterial infection and acute flare of the underlying disease in patients with rheumatoid arthritis. In contrast, there were no definite difference in the intensity of synovial fluid leukocytosis between patients with bacterial arthritis caused by living bacteria and patients with reactive arthritis probably caused by bacterial antigens.