No abstract

Judicious surgical intervention has revolutionized the management of the chronic rheumatic diseases in the last decade (Shiers, 1960;MacIntosh and Hunter, 1972;Wilson, 1972). Both reconstructive and palliative surgery have proved to be of great value in the management of patients with these disorders and these operations are today becoming commonplace. Both the indications for and the untoward effects of these operative procedures are becoming more clearly defined, and such complications as infection, loss of joint mobility, loosening of a prosthesis, and the local calcification are well recognized (Roles, 1971;Anderson, Freeman, and Swanson, 1972;Dupont and Charnley, 1972;Miller, 1972). Clearly, also, these operations carry with them the potential hazard of any anaesthetic and of the usual kind of postoperative problems such as deep venous thrombosis, pulmonary infection, or fat embolus.It is the purpose of this present short report to describe a further complication which would appear to be particularly common in certain orthopaedic procedures, namely a sudden postoperative reduction in haemoglobin concentration. To our knowledge little attention has been focused upon this problem, and, since many ofthe patients concerned are suffering from chronic diseases such as rheumatoid arthritis in which the pre-operative haemoglobin concentration itself may be low, this finding has profound clinical significance. The initial observation by one of the authors (E.P.) was that after a Shiers arthroplasty there seemed to be a marked reduction in postoperative as compared with preoperative haemoglobin concentration. Accordingly a small survey was conducted in which the pre-and postoperative haemoglobin concentrations in groups of patients undergoing different orthopaedic operations were recorded and the results are presented in this paper.Material and methods 85 patients suffering from classical or definite rheumatoid arthritis (A.R.A. criteria), all of whom had undergone operations at the Centre for Rheumatic Diseases in the previous year, were studied. Of these patients, 24 had received a Shiers arthroplasty (4 males, 20 females; mean age 54 yrs ± 3-2 S.E.M.; mean duration of arthritis 13-8 ± 19 yrs); twenty had received a McIntosh prosthesis (6 males, 14 females, mean age 51-6 yrs ± 2-8 S.E.M.; mean duration of arthritis 9-2 ± 1-4 yrs), and 21 had received anterior knee joint synovectomy (6 males, 15 females; mean age 49-8 yrs ± 2-4 S.E.M.; mean duration of arthritis 11-3 ± 2-3 yrs). These patients were selected consecutively in a retrograde fashion dating from the original observation and were not further selected in any way.In Table I the clinical details of the groups of patients studied are shown. It can be seen that these patients had severe rheumatoid arthritis denoted by the high articular indices and high erythrocyte sedimentation rate. The reduction in haemoglobin concentration (Cynamet Haemoglobin method) after operation in these groups of patients was compared with a group of 20 patients who had undergone sup...

SummaryWe have studied, over a wide range of dilutions using techniques of clot weight, thrombelastography and scanning electron microscopy, the physical properties of a blood clot formed in vitro when fresh blood was diluted with gelatinbased colloid solutions compared with crystalloid controls. The colloid solutions tested (3.5% polygeline (Haemaccel) and 4% succinylated gelatin (Gelofusine)) produced clots that had reduced median weight (P:0.001 and P:0.018, respectively) and reduced mean shear modulus (P:0.001) compared with crystalloid controls. Scanning electron microscopy showed that the fibrin formed a less extensive mesh in the presence of the gelatin-based colloids compared with crystalloid. Reduction in clot quality with gelatin-based colloids has not been noted previously and further work is needed to ascertain if this occurs in vivo as these solutions are used frequently in patients who require full haemostatic competence. (Br. J. Anaesth. 1998; 80: 204-207) Keywords: blood, coagulation; blood, colloids; fluids, i.v.; blood, haemostasis; blood, replacement; measurement techniques, thrombelastography Plasma substitutes containing degraded and modified gelatin are being used increasingly in prehospital, resuscitation, perioperative and intensive care situations. Often they are the fluid of choice in patients with uncontrolled haemorrhage both before blood transfusion and in conjunction with transfusion of packed cells. Unlike the dextran and starch solutions, so far they have been considered as having no significant effect on clotting mechanisms following studies based principally on clotting times. [1][2][3][4] While measuring whole blood coagulation times after in vitro dilution with colloids we noted a striking difference in clot quality compared with that seen with dilution using crystalloid. Our preliminary findings have been reported previously.5 In this article we describe more detailed investigations using clot weights, haematological analysis, thrombelastography and scanning electron microscopy, and include a description of the dose-response effect of varying degrees of dilution using regression analysis. Materials and methodsWherever fresh whole blood was used, care was taken to avoid prolonged venous stasis, venepuncture from the same site or delays in pipetting, and experiments were conducted under strict temperature control.CLOT WEIGHTS A total of 35 fresh whole blood samples were diluted to 15%, 30%, 45%, 60% and 75% with 0.9% sodium chloride and Ringer's solution (controls) or the test substances, 4% succinylated gelatin (Gelofusine, B. Braun (Medical) Ltd) and 3.5% polygeline solution (Haemaccel, Hoescht UK Ltd). After dividing each sample into test and control, the total volume of each sample after dilution was 5 ml. Clot weights were measured using the method described by Macfarlane.6 Because the clots would not adhere to a glass rod the test was modified by separating the clot from plasma on gauze in a funnel. Clots were weighed on an electronic balance and then examined physica...

, 5 and the LJP 394-90-09 Investigator ConsortiumObjective. To investigate whether treatment with abetimus delays renal flare in patients with lupus nephritis. Secondary objectives included evaluation of the effect of abetimus on C3 levels, anti-doublestranded DNA (anti-dsDNA) antibody levels, use of high-dose corticosteroids and/or cyclophosphamide, and major systemic lupus erythematosus (SLE) flare.Methods. We conducted a randomized, placebocontrolled study of treatment with abetimus at 100 mg/week for up to 22 months in SLE patients. Three hundred seventeen patients with a history of renal flare and anti-dsDNA levels >15 IU/ml were randomized to a treatment group (158 abetimus, 159 placebo); 298 (94%) were enrolled in the intent-to-treat ( Abetimus treatment decreased anti-dsDNA antibody levels (P < 0.0001), and reductions in anti-dsDNA levels were associated with increases in C3 levels (P < 0.0001). More patients in the abetimus group experienced >50% reductions in proteinuria at 1 year, compared with the placebo group (nominal P ‫؍‬ 0.047). Trends toward reduced rates of renal flare and major SLE flare were noted in patients treated with abetimus who had impaired renal function at baseline. Treatment with abetimus for up to 22 months was well tolerated.Conclusion. Abetimus at 100 mg/week significantly reduced anti-dsDNA antibody levels but did not significantly prolong time to renal flare when compared with placebo. Multiple positive trends in renal end points were observed in the abetimus treatment group.There is a substantial body of evidence implicating anti-double-stranded DNA (anti-dsDNA) antibodies in the pathogenesis of lupus nephritis. Anti-dsDNA antibodies are rarely found in individuals without SLE (1-4), and their presence is diagnostic for SLE and prognostic for development of lupus nephritis. The presence of anti-dsDNA antibodies often correlates with active renal disease (5-8). Anti-dsDNA antibodies are concentrated in the kidneys of SLE patients and often have a much higher avidity for dsDNA than do antibodies in the circulation (9,10). Well-controlled studies have demonstrated a strong correlation between rises in anti-dsDNA antibody levels and subsequent exacerbations of . Similarly, reductions in antiClinicalTrials.gov identifier: NCT00035308.

IntroductionThe objective of this study was to evaluate the long-term safety and efficacy of tabalumab, a monoclonal antibody that neutralizes membrane-bound and soluble B-cell-activating factor, in rheumatoid arthritis (RA) patients.MethodsPatients with RA who completed one of two 24-week randomized controlled trials (RCTs) participated in this 52-week, flexible-dose, open-label extension study. Patients in RCT1 received intravenous placebo, 30-mg tabalumab or 80-mg tabalumab every 3 weeks, and patients in RCT2 received subcutaneous placebo or 1-, 3-, 10-, 30-, 60- or 120-mg tabalumab every 4 weeks (Q4W). Regardless of prior treatment, all patients in this study received subcutaneous 60-mg tabalumab Q4W for the first 3 months, then a one-time increase to 120-mg tabalumab Q4W (60-mg/120-mg group) and a one-time decrease to 60-mg tabalumab Q4W per patient was allowed (60-mg/120-mg/60-mg group).ResultsThere were 182 patients enrolled: 60 mg (n = 60), 60/120 mg (n = 121) and 60/120/60 mg (n = 1). Pretabalumab baseline disease activity was generally higher in the 60-mg/120-mg group. There was a higher frequency of serious adverse events and treatment-emergent adverse events, as well as infections and injection-site reactions, in the 60-mg/120-mg group. One death unrelated to the study drug occurred (60-mg/120-mg group). In both groups, total B-cell counts decreased by approximately 40% from the baseline level in the RCT originating study. Both groups demonstrated efficacy through 52 weeks of treatment relative to baseline pretabalumab disease activity based on American College of Rheumatology criteria improvement ≥20%, ≥50% and ≥70%; European League against Rheumatism Responder Index in 28 joints; Disease Activity Score in 28 joints–C-reactive protein; and Health Assessment Questionnaire–Disability Index.ConclusionsWith long-term, open-label tabalumab treatment, no unexpected safety signals were observed, and B-cell reductions were consistent with previous findings. Despite differences in RCT originating studies, both groups demonstrated an efficacy response through the 52-week extension.Trial registrationClinicalTrials.gov Identifier: NCT00837811 (registered 3 February 2009).Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-014-0415-2) contains supplementary material, which is available to authorized users.