ABSTRACT
In elderly patients cognitive dysfunction and other adverse events (AEs) can impair the outcome of surgical procedures. As THR is performed with increasing frequency in aging populations, it is important to know the impact of these problems on the postoperative result. In this prospective cohort study 60 patients older than 65 years (66.7% female, 33.3% male) who received THR were included. The cognitive function was measured preoperatively, one week and six months postoperatively by the mini-mental state test (MMSE). Shortly after surgery 4 patients (6.7%) developed postoperative cognitive dysfunction, which has recovered at six-months-follow-up. In 41 patients (68.3%) AEs were recorded. Postoperative anemia occurred as the most common AE (n=32; 53.3%). During hospital stay older patients are at an increased risk for AEs. The incidence of postoperative cognitive dysfunction was observed less often than expected. Further research is necessary to assess the effect of early interventions in case of cognitive dysfunction. With use of a simple and quickly performed test like the MMSE patients can be effectively screened for impaired cognitive function. Secure identification of those patients is mandatory to avoid complications with harmful long-term effects.
Subject(s)
Aging , Arthroplasty, Replacement, Hip/adverse effects , Arthroplasty, Replacement, Hip/psychology , Cognition Disorders/epidemiology , Delirium/etiology , Postoperative Complications/epidemiology , Aged , Aged, 80 and over , Cognition Disorders/etiology , Delirium/epidemiology , Delirium/prevention & control , Female , Follow-Up Studies , Geriatric Assessment , Humans , Incidence , Male , Mental Status Schedule , Postoperative Period , Precipitating Factors , Prospective Studies , Quality of Life , Risk Factors , Socioeconomic FactorsABSTRACT
Rheumatoid arthritis (RA) is a chronic, inflammatory joint disease of unknown etiology and pronounced interpatient heterogeneity. To characterize RA at the molecular level and to uncover pathomechanisms, we performed genome-wide gene expression analysis. We identified a set of 1,054 genes significantly deregulated in pair-wise comparisons between RA and osteoarthritis (OA) patients, RA and normal donors (ND), or OA and ND. Correlation analysis revealed gene sets regulated identically in all three groups. As a prominent example secreted phosphoprotein 1 (SPP1) was identified to be significantly upregulated in RA compared with both OA and ND. SPP1 expression was found to correlate with genes expressed during an inflammatory response, T-cell activation and apoptosis, suggesting common underlying regulatory networks. A subclassification of RA patients was achieved on the basis of proteoglycan 4 (PRG4) expression, distinguishing PRG4 high and low expressors and reflecting the heterogeneity of the disease. In addition, we found that low PRG4 expression was associated with a more aggressive disease stage, which is in accordance with PRG4 loss-of-function mutations causing camptodactyly-arthropathy-coxa vara-pericarditis syndrome. Altogether we provide evidence for molecular signatures of RA and RA subclasses, sets of new candidate genes as well as for candidate gene networks, which extend our understanding of disease mechanisms and may lead to an improved diagnosis.
Subject(s)
Arthritis, Rheumatoid/genetics , Gene Expression Profiling , Adult , Aged , Aged, 80 and over , Arthritis, Rheumatoid/pathology , Female , Humans , Male , Middle Aged , Proteoglycans/genetics , Proteoglycans/metabolismSubject(s)
Arecaceae , Conservation of Natural Resources/economics , Plant Oils/economics , Biodiversity , Palm OilABSTRACT
Before elective surgery, it is mandatory that a precise history be taken to detect increased hemorrhagic diathesis and that thrombocytes, Quick/INR, and aPTT be determined. If pathological levels are found, further laboratory tests are necessary after frequent causes (e.g., liver cirrhosis) have been excluded. Single-factor analysis for the von Willebrand's factor antigen and if necessary further tests to check for von Willebrand's syndrome (multimeric analysis) as well as platelet function tests should be performed.Dysfibrinogenemia is a rare coagulation disorder, which causes elevated INR. It shows a wide spectrum of clinical manifestations including thrombophilia, excessive bleeding, and even asymptomatic cases. We present a 72-year-old patient with asymptomatic dysfibrinogenemia who needed hip replacement due to arthrosis. Lowered fibrinogen levels were substituted prior to operation and the clinical course afterwards was uneventful under additional prophylactic anticoagulation in order to prevent thrombosis. The case report illustrates the interdisciplinary teamwork which is very important in the management of patients with coagulation disorders.
Subject(s)
Afibrinogenemia/complications , Afibrinogenemia/therapy , Anticoagulants/administration & dosage , Arthroplasty, Replacement, Hip/adverse effects , Premedication/methods , Thrombosis/etiology , Thrombosis/prevention & control , Afibrinogenemia/diagnosis , Aged , Female , Humans , Perioperative Care/methods , Rare Diseases/prevention & control , Treatment OutcomeABSTRACT
AIMS: The introduction of clearly defined histopathological criteria for a standardised evaluation of the periprosthetic membrane, which can appear in cases of total joint arthroplasty revision surgery. METHODS: Based on histomorphological criteria, four types of periprosthetic membrane were defined: wear particle induced type (detection of foreign body particles; macrophages and multinucleated giant cells occupy at least 20% of the area; type I); infectious type (granulation tissue with neutrophilic granulocytes, plasma cells and few, if any, wear particles; type II); combined type (aspects of type I and type II occur simultaneously; type III); and indeterminate type (neither criteria for type I nor type II are fulfilled; type IV). The periprosthetic membranes of 370 patients (217 women, 153 men; mean age 67.6 years, mean period until revision surgery 7.4 years) were analysed according to the defined criteria. RESULTS: Frequency of histopathological membrane types was: type I 54.3%, type II 19.7%, type III 5.4%, type IV 15.4%, and not assessable 5.1%. The mean period between primary arthroplasty and revision surgery was 10.1 years for type I, 3.2 years for type II, 4.5 years for type III and 5.4 years for type IV. The correlation between histopathological and microbiological diagnosis was high (89.7%), and the inter-observer reproducibility sufficient (85%). CONCLUSION: The classification proposed enables standardised typing of periprosthetic membranes and may serve as a tool for further research on the pathogenesis of the loosening of total joint replacement. The study highlights the importance of non-infectious, non-particle induced loosening of prosthetic devices in orthopaedic surgery (membrane type IV), which was observed in 15.4% of patients.
Subject(s)
Arthroplasty, Replacement, Hip/adverse effects , Arthroplasty, Replacement, Knee/adverse effects , Foreign-Body Reaction/pathology , Adult , Aged , Aged, 80 and over , Arthroplasty, Replacement, Hip/methods , Arthroplasty, Replacement, Knee/methods , Female , Foreign-Body Reaction/classification , Foreign-Body Reaction/etiology , Giant Cells, Foreign-Body/pathology , Granulation Tissue/pathology , Hip Joint/pathology , Humans , Knee Joint/pathology , Male , Middle Aged , Prosthesis Failure , Prosthesis-Related Infections/complications , Prosthesis-Related Infections/pathology , ReoperationABSTRACT
After 10 years, loosening of total joint endoprostheses occurs in about 3 to 10 percent of all patients, requiring elaborate revision surgery. A periprosthetic membrane is routinely found between bone and loosened prosthesis. Further histomorphological examination allows determination of the etiology of the loosening process. Aim of this study is the introduction of clearly defined histopathological criteria for a standardized evaluation of the periprosthetic membrane. Based on histomorphological criteria and polarized light microscopy, four types of the periprosthetic membrane were defined: periprosthetic membrane of wear particle type (type I), periprosthetic membrane of infectious type (type II), periprosthetic membrane of combined type (type III), periprosthetic membrane of indifferent type (type IV). Periprosthetic membranes of 268 patients were analyzed according to the defined criteria. The correlation between histopathological and microbiological diagnosis was high (89%, p<0,001), the inter-observer reproducibility was sufficient (95%). This classification system enables a standardized diagnostic procedure and therefore is a basis for further studies concerning the etiology of and pathogenesis of prosthesis loosening.
Subject(s)
Arthroplasty, Replacement, Hip/adverse effects , Hip Joint/pathology , Knee Joint/pathology , Knee Prosthesis/adverse effects , Prosthesis Failure , HumansABSTRACT
OBJECTIVE: The pathogenesis of periprosthetic bone loss in aseptic and septic prosthesis loosening is unclear. There is considerable evidence that macrophages and osteoclasts play a key role in focal bone erosion and osteolysis around the prosthesis. RANKL (receptor activator of nuclear factor kappaB ligand) was shown to be a potent osteoclastogenic factor, and to be involved in bone destruction of myeloma and rheumatoid arthritis patients. Osteoprotegerin (OPG) is the natural RANKL inhibitor and may prevent periprosthetic bone loss. METHODS: The presence and distribution of RANKL, its receptor RANK and OPG in the periprosthetic interface of septically (n = 5) and aseptically (n = 6) loosened prostheses was examined by immunohistochemistry and immunoblotting. Additionally, the immunophenotype of the inflammatory infiltrate was determined [CD3, CD68, Ki-67, tartrate-resistant acid posphatase (TRAP)]. RESULTS: Aseptic and septic cases revealed a different histopathologic pattern. However, in all cases RANKL and RANK could be demonstrated in macrophages and giant cells. In addition, RANKL detected by immunoblot analysis proved to have the same molecular weight as a recombinant RANKL used as a control (31 kD and approximately 48 kD). OPG was detected in aseptic loosening, where macrophages showed a strong staining, but multinucleated giant cells were only weakly stained. A weak OPG staining was also observed in septic loosening. CONCLUSION: The pathogenesis of bone loss in septic loosening remains unclear, because the septic membrane bears few macrophages and giant cells, and half of them express OPG. In aseptic loosening, macrophages might not be stimulated by RANKL as a result of OPG expression. But multinucleated giant cells may be activated, as they hardly express OPG. They might be responsible for periprosthetic bone loss in aseptic loosening as a result of their RANKL and RANK expression.
Subject(s)
Carrier Proteins/metabolism , Hip Prosthesis , Knee Prosthesis , Membrane Glycoproteins/metabolism , Osteolysis/metabolism , Prosthesis Failure , Prosthesis-Related Infections/metabolism , Aged , Aged, 80 and over , Arthroplasty, Replacement, Hip , Arthroplasty, Replacement, Knee , Blotting, Western , Female , Giant Cells/metabolism , Giant Cells/pathology , Glycoproteins/metabolism , Humans , Immunohistochemistry , Macrophages/metabolism , Macrophages/pathology , Male , Middle Aged , Osteolysis/microbiology , Osteolysis/pathology , Osteoprotegerin , Prosthesis-Related Infections/microbiology , Prosthesis-Related Infections/pathology , RANK Ligand , Receptor Activator of Nuclear Factor-kappa B , Receptors, Cytoplasmic and Nuclear/metabolism , Receptors, Tumor Necrosis FactorABSTRACT
In addition to systemic medication,physiotherapy, and operative measures, intraarticular therapy with corticosteroids (iaST) is a well established treatment for juvenile idiopathic arthritis (JIA). IaST is indicated in children whose inflamed joints do not respond sufficiently to systemic antiarthritic drugs and is normally carried out under in-patient conditions. Triamcinolone hexacetonide (TH) is the drug of choice for iaST because of its well documented, long-lasting effects. In younger children or those who require simultaneous injections into multiple joints, a short general anesthesia is useful, while single injections in older children can be administered after topical application of a local anesthetic. Intensive physiotherapy after iaST is important for regaining mobility lost due to the arthritis, and 2 or 3 days of post-injection rest should be adhered to after iaST of joints of the lower extremities. Several studies demonstrate long-lasting remission in the majority of the injected joints in JIA patients, with good pain-relief, improved mobility, and a significant delay in further joint destruction in comparison with joints in which the synovitis could not be adequately controlled. Various sub-types of JIA have been shown to respond differently to iaST. Intraarticular steroids can also be used to treat coxitis, since recent data failed to show a subsequent increase in the rate of femoral head necrosis. Septic arthritis, the most feared complication after iaTH, seems to be extremely rare in children. Other complications, like periarticular calcifications or subcutaneous atrophy, also occur only rarely, provided the steroid is injected correctly. The present data indicate that iaST is an effective and safe treatment for JIA. The therapeutic approach to children with JIA is multidisciplinary, and these young patients should be treated in specialised centres.
Subject(s)
Arthritis, Juvenile/drug therapy , Triamcinolone Acetonide/analogs & derivatives , Triamcinolone Acetonide/administration & dosage , Adolescent , Child , Dose-Response Relationship, Drug , Female , Follow-Up Studies , Humans , Injections, Intra-Articular , Male , Pain Measurement , Physical Therapy Modalities , Treatment Outcome , Triamcinolone Acetonide/adverse effectsABSTRACT
The following is a proposition for a simple histopathological classification system to measure inflammation in synovial tissue. This synovitis-score is employed in conventionally stained routine sections, and is applicable to every kind of synovitis, irrespective of etiology and including the following relevant morphological alterations. First: hyperplasia/enlargement of synovial lining cell layer. Second: activation of resident cells/synovial stroma. Third: inflammatory infiltration. All defined histopathological qualities are graded from absent (0), slight (1) and moderate (2) to strong (3), with summaries ranging from 0 to 9. 0 to 1 corresponds to no synovitis (inflammatory grade = 0), 2 to 3 to a slight synovitis (inflammatory grade 1), 4 to 6 to a moderate synovitis (inflammatory grade 2), and 7 to 9 to a strong synovitis (inflammatory grade 3). Using this score, we analyzed 308 random specimens of synovial tissue from degenerative (osteoarthritis (OA)) and inflammatory joint diseases - reactive arthritis (ReA), psoriasis arthritis (PA) and rheumatoid arthritis (RA) - as well as synovial tissue from healthy individuals. The mean grade given to synovitis of RA turned out to be significantly higher than the mean grade of OA (p < 0.0005) and of healthy controls (p < 0.0005). On the contrary, no significant differences could be found between the mean grades of synovitis scores from patients with RA and those with PA and ReA. Another comparison between RA-synovitis types I and II according to the Stiehl classification resulted in type I (p < 0.0005), showing significantly higher values of inflammatory infiltration, and type II (p = 0.037), showing significantly higher values of stroma activation. Since in OA, synovitis is regarded as a result of degenerative cartilage destruction whereas in inflammatory joint diseases (RA, PA, ReA), synovitis is regarded to be the cause of cartilage destruction, it can be concluded that scores with considerable high values indicate the pathogenetic potential of synovitis and that the inflammatory score may be helpful in estimating the destructive potential of synovitis at the same time. Furthermore, the comparison of the score data with the Stiehl RA-synovitis types shows that the score enables us to discriminate the morphological peculiarities of the synovitis types. In experimental pathology, it could provide standardized information on molecular synovial tissue analyses where a correlation of molecular with morphological data is essential. In diagnostic pathology, this synovitis score (in combination with other typing systems) could provide basic and standardized information concerning the degree of inflammatory alterations in synovial tissue.
Subject(s)
Arthritis/pathology , Pathology, Clinical/methods , Synovitis/pathology , Arthritis/complications , Chronic Disease , Female , Humans , Male , Observer Variation , Prohibitins , Reproducibility of Results , Synovitis/classification , Synovitis/etiologyABSTRACT
Post-traumatic stiffness of the elbow joint in children after unreduced multifragmentary fractures of the distal humerus can be successfully treated by interposition arthroplasty. A case with long-term follow up is described, and the literature discussed.
Subject(s)
Ankylosis/surgery , Arthroplasty/methods , Elbow Injuries , Fractures, Comminuted/surgery , Fractures, Malunited/surgery , Humeral Fractures/surgery , Postoperative Complications/diagnostic imaging , Adolescent , Adult , Aged , Ankylosis/diagnostic imaging , Child , Elbow Joint/diagnostic imaging , Elbow Joint/surgery , Female , Follow-Up Studies , Fractures, Comminuted/diagnostic imaging , Fractures, Malunited/diagnostic imaging , Humans , Humeral Fractures/diagnostic imaging , Joint Instability/diagnostic imaging , Middle Aged , Radiography , ReoperationABSTRACT
OBJECTIVE: To determine whether circulating levels of insulin-like growth factors and their binding proteins are altered in patients with adult onset rheumatoid arthritis. METHODS: Plasma-levels of insulin-like growth factor-I (IGF-I), IGF-II, IGF-binding-protein 2 (IGFBP-2), and IGFBP-3 were measured by radioimmunoassay in 53 patients with clinically active rheumatoid arthritis (RA) and in 51 control subjects. RESULTS: In RA patients plasma levels of IGF-II were lower (601 +/- 34 vs. 731 +/- 32 micrograms/L (mean +/- SEM); p = 0.005; Mann-Whitney rank sum test) than in age- and sex-matched controls (n = 30 per group). In contrast, plasma levels of IGFBP-2 (412 +/- 40 vs. 254 +/- 20 micrograms/L; p = 0.003) and IGFBP-3 were elevated in RA patients (3.34 +/- 0.19 vs. 2.87 +/- 0.21 mg/L; p = 0.019) as compared with the matched controls. The molar ratio of IGF-I to IGFBP-3 was significantly reduced in subjects with RA (0.18 +/- 0.01 vs. 0.24 +/- 0.02; p = 0.008). Furthermore, in RA patients plasma levels of IGFBP-2 were positively (r = 0.45), and levels of IGF-2 negatively (r = -0.45) correlated with circulating levels of C-reactive protein (p < 0.01 in both cases; Spearman rank correlation). CONCLUSION: Increased levels of IGFBPs in RA may result in the reduced availability of free IGFs that can bind to IGF receptors. The observed changes in the IGF system may thus participate in the catabolic processes in rheumatoid arthritis.
Subject(s)
Arthritis, Rheumatoid/blood , Insulin-Like Growth Factor Binding Proteins/blood , Somatomedins/analysis , Adolescent , Adult , Aged , Aged, 80 and over , C-Reactive Protein/analysis , Female , Humans , Insulin-Like Growth Factor Binding Protein 2/blood , Insulin-Like Growth Factor Binding Protein 3/blood , Insulin-Like Growth Factor I/analysis , Insulin-Like Growth Factor II/analysis , Male , Middle AgedABSTRACT
Successful transplantation of autologous chondrocytes for repair of articular cartilage defects requires an undisturbed matrix-synthesis of the transplanted cells. This, in turn, is dependent on the composition of the synovial fluid (SF) of the respective joint. We addressed the question whether analysis of a patient's SF can predict the rate of matrix-synthesis of articular cartilage exposed to this SF in vitro. SF was obtained from 115 patients with disorders of the knee, including gonarthrosis (n = 44), meniscal tears (n = 10), rheumatoid arthritis (n = 53), and reactive arthritides (n = 8). In the SF, the following parameters were determined: Interleukin-1 beta, IL-6, IL-8, IL-1-RA, TNF alpha, Insulin-like growth-factor I (IGF-I), IGF-II, IGF-binding protein-2 (IGFBP-2), IGFBP-3 as well as total proteinase activity and total collagenase activity. To assess the effect of SF on the matrix synthesis of articular chondrocytes, bovine cartilage was incubated in the presence of SF, and the rate of proteoglycan synthesis subsequently determined. In some cases, a monoclonal antibody directed against IGF-I was added. SF from patients with OA or trauma, respectively, stimulated PG-synthesis of bovine cartilage more markedly than did SF from patients with rheumatic arthritides. On the average, 60 percent of the SF-induced increase of cartilage matrix synthesis could be titrated out by an anti-IGF-I-AB. The best predictor for the SF-effects on PG-synthesis of exposed cartilage was the proportion of free IGF-I (r = 0.573, p < 0.001, Spearman rank correlation) followed by the SF-concentrations of IGF-I (with a positive sign), IGFBP-3, IL-1 beta, and TNF alpha (all with a negative sign). According to our data, IGF-I is the most important anabolic factor in human SF with respect to cartilage PG-synthesis. The proportion of free IGF-I seems to be of special importance in this regard. Low SF-levels of free IGF-I could be identified as a possible risk-factor for a sub-optimal protoeglycan synthesis of chondrocytes exposed to this synovial milieu.
Subject(s)
Chondrocytes/transplantation , Cytokines/physiology , Extracellular Matrix Proteins/biosynthesis , Growth Substances/physiology , Knee Joint/surgery , Synovial Fluid/physiology , Adult , Aged , Aged, 80 and over , Animals , Cattle , Chondrocytes/pathology , Female , Humans , Knee Joint/pathology , Male , Middle Aged , Prognosis , Proteoglycans/metabolism , Regeneration/physiology , Synovial Fluid/chemistry , Wound Healing/physiologyABSTRACT
OBJECTIVE: Methotrexate (MTX) has become the disease modifying drug of choice for the treatment of rheumatoid arthritis (RA). Direct effects of MTX on articular cartilage in vivo and in vitro were studied to determine possible adverse effects of the drug. METHODS: For in vitro experiments, adult bovine articular cartilage explants were cultured in the presence of MTX (0 to 100 microM), and effects on DNA and matrix metabolism were studied. For in vivo studies, 48 adult female rabbits were treated with MTX (30 mg/kg/week intramuscularly) or placebo, respectively, for up to 12 weeks, and effects on the cartilage of the femoral condyles were assessed. RESULTS: In vitro, MTX dose dependently increased the uptake of [3H]-thymidine, and decreased incorporation of [3H]-d-uridine into chondrocytes with a half maximal effect at 0.03 microM, suggesting inhibition of thymidylate-synthetase activity by the drug. MTX also dose dependently reduced the proportion of chondrocytes in S-phase, as determined by flow cytometry. MTX did not affect LDH release from chondrocytes or the proportion of viable cells, nor did it change the rate of protein synthesis, proteoglycan synthesis, proteoglycan breakdown, or the hydrodynamic size of newly synthesised proteoglycans. In vivo, MTX did not appreciably affect proteoglycan synthesis of the chondrocytes, proteoglycan content of the cartilage matrix, density of the chondrocyte population, or histological integrity of the cartilage. CONCLUSIONS: The data suggest the absence of major adverse effects by MTX on articular cartilage proteoglycan metabolism. Chondrocyte DNA metabolism seems to be changed by MTX only in concentrations and exposition periods clearly exceeding those found in synovial fluid of RA patients receiving the commonly prescribed doses of the drug.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Cartilage, Articular/drug effects , Methotrexate/pharmacology , Animals , Anti-Inflammatory Agents/pharmacokinetics , Cartilage, Articular/metabolism , Cattle , Cell Division/drug effects , Culture Techniques , DNA/metabolism , Dose-Response Relationship, Drug , Female , Hindlimb , Injections, Intramuscular , Methotrexate/pharmacokinetics , Proteoglycans/analysis , Rabbits , Steroids , Synovial Fluid/chemistry , Synovial Fluid/metabolismABSTRACT
To determine whether systemic administration of methotrexate (MTX) can prevent joint destruction in experimental osteoarthrosis (OA) in rabbits, the disorder was induced unilaterally in the knee joints of 40 rabbits by partial medial meniscectomy and sectioning of the medial collateral and both cruciate ligaments. A sham operation (arthrotomy only) was performed in another four animals. Effects on the cartilage of the femoral condyles were studied after 6 and 12 weeks. Twelve weeks after induction, femoral and tibial osteophyte formation was demonstrated on radiographs in all cases. Marked cartilage damage was found histologically (median Mankin score 10 vs 1 for non-operated controls; P < 0.05, Wilcoxon test). Cartilage proteoglycan (GAG) content (dye binding assay) was reduced in operated joints [63 +/- 8 (mean +/- SEM) vs 75 +/- 6 micrograms chondroitin sulfate/mg cartilage wet weight], and the leukocyte count in the joints was elevated (226 +/- 14 vs 7 +/- 3 leukocytes per microliter joint aspirate after injection of 0.5 ml saline solution; both P < 0.05, Wilcoxon test). The rate of GAG synthesis was unchanged (ex vivo labelling with 35S-sulfate). Treatment with MTX (30 mg x kg body weight-1 x week-1 i.m., starting 12 h postoperatively) reduced cartilage damage (median Mankin score 8 vs 10 for placebo, P < 0.05, Mann-Whitney U-test), but had no significant effect on the other parameters tested. No significant MTX effects were observed on cartilage from nonoperated joints. Our data indicate that MTX may have a limited therapeutic effect in experimental OA in the rabbit.
Subject(s)
Antirheumatic Agents/pharmacology , Methotrexate/pharmacology , Osteoarthritis/pathology , Animals , Cartilage, Articular/pathology , Disease Models, Animal , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Injections, Intramuscular , Knee Joint/pathology , RabbitsABSTRACT
Severe hyponatremia may be chronic (days) or acute (hours), symptomatic or asymptomatic. Severe chronic symptomatic hyponatremia (serum sodium concentration < 110 to 115 mM/liter) occurs most commonly in the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The treatment of this hyponatremia is a challenge to practicing physicians, in part because an overly rapid correction of hyponatremia may cause brain damage. The latter sometimes takes the form of central pontine myelinolysis (CPM). On the basis of available clinical and experimental literature, the rate of correction of this symptomatic hyponatremia should be no more than 0.5 mM per liter per hour, and the initial treatment should be halted once a mildly hyponatremic range of the serum sodium concentration has been reached (approximately 125 to 130 mM/liter). In contrast, severe chronic asymptomatic hyponatremia may be treated sufficiently by a fluid restriction. On the other hand, severe symptomatic acute hyponatremia should be treated promptly and rapidly, using hypertonic saline, to initially reach a mildly hyponatremic level.
Subject(s)
Hyponatremia/diagnosis , Hyponatremia/therapy , Adolescent , Diagnosis, Differential , Humans , Hyponatremia/blood , Inappropriate ADH Syndrome/blood , Inappropriate ADH Syndrome/diagnosis , Inappropriate ADH Syndrome/therapy , Male , Sodium/blood , Water/administration & dosageABSTRACT
The objective of this study was to quantify insulin-like growth factor (IGF) binding proteins (IGFBPs) in the synovial fluid (SF) and plasma of patients with rheumatic diseases and to study the role of these proteins in the regulation of cartilage proteoglycan (PG) synthesis. Immunological determination of IGFBP-2, IGFBP-3, IGF-I, IGF-II, interleukin-1 beta (IL-1 beta) and tumour necrosis factor alpha (TNF alpha) was undertaken in the SF and plasma of 115 patients with rheumatoid arthritis (RA; n = 53), osteoarthritis (OA; n = 44) and other rheumatic disorders. We also determined the effects of SF on bovine cartilage PG synthesis in culture. IGFBP-2 and IGFBP-3 were elevated in the plasma (by 38% and 28%, respectively) and SF (by 56% and 59%, respectively) of patients with RA compared to age- and sex-matched OA controls (determined by RIA and confirmed by Western ligand blot). IGF-I and IGF-II did not differ significantly between the two groups. OA SF, and, to a lesser extent, RA SF stimulated cartilage PG synthesis in culture, and more than 60% of this activity was neutralised by a specific monoclonal anti-IGF-I antibody. Human IGFBP-3 dose-dependently inhibited the stimulation of cartilage PG synthesis effected by SF or human IGF-I. In RA patients, the SF concentration of IGFBP-3 was positively correlated with SF levels of IL-1 beta and TNF alpha, with the serum levels of C-reactive protein and with the erythrocyte sedimentation rate. We concluded that IGF-I is, under the conditions studied, the most important anabolic factor in human SF with respect to articular cartilage PG synthesis. The bioactivity of IGF-I in joints is modulated by IGFBP-3, which is elevated in RA SF compared to OA SF. Elevated IGFBP-3 in RA SF may reduce the availability of IGF-I to articular chondrocytes, thus interfering with cartilage PG synthesis in RA.
Subject(s)
Arthritis, Rheumatoid/metabolism , Cartilage/metabolism , Insulin-Like Growth Factor Binding Protein 3/biosynthesis , Insulin-Like Growth Factor I/pharmacology , Proteoglycans/biosynthesis , Synovial Fluid/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Animals , Arthritis, Rheumatoid/pathology , Cartilage/drug effects , Cattle , Culture Techniques , Drug Antagonism , Female , Humans , Insulin-Like Growth Factor Binding Protein 3/pharmacology , Male , Middle AgedABSTRACT
OBJECTIVE: To determine whether the activity of cartilage-degrading enzymes in the synovial fluid (SF) of patients with rheumatoid arthritis and other joint diseases is correlated with the concentration of cytokines in the SF. METHODS: Cytokines and cartilage-degrading enzymes were determined in the SF of 97 patients with various disorders involving the knee joints (rheumatoid arthritis (RA) n 44; osteoarthritis (OA) n 35; meniscal trauma (Men) n 10; reactive arthritides (ReA) n 8). In these samples we measured the concentrations of interleukin-1 alpha and beta, IL-1-receptor antagonist (IL-1ra), IL-6, IL-8, tumor necrosis factor alpha (TNF alpha; all by ELISA), collagenase-activity and caseinase-activity (by substrate assays). RESULTS: With the exception of IL-1 alpha and IL-6, cytokine-concentrations were significantly higher in RA than in OA SF-samples (p < 0.05; ANOVA on ranks). IL-1ra, IL-6, and IL-1 beta were correlated best with the collagenase-activity in the SF (r = 0.63; 0.57; 0.55; Spearman's rank correlation), while IL-1 beta (r = 0.53) and IL-1ra (r = 0.52) were best correlated with the caseinase-activity in the samples. The SF-concentration of IL-1ra was well correlated with the levels of IL-6, IL-1 beta, II-8, and TNF alpha (r from 0.73 to 0.66; all p < 0.005), but not with IL1 alpha. The molar ratio of IL-1 to IL-1ra in the SF was neither correlated with the activity of collagenase nor caseinase. IL-1 beta and IL-1ra in the SF were positively correlated with the erythrocyte sedimentation rate (ESR). CONCLUSIONS: The determination of IL-1 beta and IL-1ra in the SF of patients with joint disorders as examined in this study seems to allow to a certain extent a prediction of the collagenase- and caseinase-activity contained in the diseased joint. We would favor.