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Contains fulltext : 57325.pdf (Publisher’s version ) (Open Access) Antibodies against cyclic citrullinated peptide (CCP) and rheumatoid factors (RFs) have been demonstrated to predate the onset of rheumatoid arthritis ( RA) by years. A nested case control study was performed within the Northern Sweden Health and Disease study cohort to analyse the presence of shared epitope ( SE) genes, defined as HLA-DRB1* 0404 or DRB1* 0401, and of anti-CCP antibodies and RFs in individuals who subsequently developed RA. Patients with RA were identified from among blood donors whose samples had been collected years before the onset of symptoms. Controls matched for age, sex, and date of sampling were selected randomly from the same cohort. The SE genes were identified by polymerase chain reaction sequence-specific primers. Anti-CCP2 antibodies and RFs were determined using enzyme immunoassays. Fifty-nine individuals with RA were identified as blood donors, with a median antedating time of 2.0 years interquartile range 0.9 - 3.9 years) before presenting with symptoms of RA. The sensitivity for SE as a diagnostic indicator for RA was 60% and the specificity was 64%. The corresponding figures for anti-CCP antibodies were 37% and 98%, and for RFs, 17 - 42% and 94%, respectively. In a logistic regression analysis, SE ( odds ratio [OR] = 2.35), anti-CCP antibodies ( OR = 15.9), and IgA-RF ( OR = 6.8) significantly predicted RA. In a combination model analysis, anti-CCP antibodies combined with SE had the highest OR (66.8, 95% confidence interval 8.3 - 539.4) in predicting RA, compared with anti-CCP antibodies without SE ( OR = 25.01, 95% confidence interval 2.8 - 222.2) or SE without anti-CCP antibodies ( OR = 1.9, 95% confidence interval 0.9 - 4.2). This study showed that the presence of anti-CCP antibodies together with SE gene carriage is associated with a very high relative risk for future development of RA.

SummaryA segment of the inferior vena cava was replaced by an expanded polytetrafluoroethylene graft in 13 dogs. Five of them served as a control group, while the other 8 were moderately or severely defibrinogenated with subcutaneous batroxobin. Plasma fibrinogen decreased to extremely low values throughout the experiment in the defibrinogenated dogs except in the moderately treated group in which it temporarily rose to 0.72-0.87 g/1 on the first postoperative day.Scanning electron microscopic observations of the haemostatic clot formed at the anastomoses of the graft revealed no significant morphological differences in platelet adhesion and/or aggregation between the three groups. These findings confirmed that platelets play a key role in primary haemostasis during defibrinogenation.The fibrin network was slightly diminished and only short fibrin filaments could be seen in the moderately and severely defibrinogenated groups respectively. These differences in composition of the clots are discussed in relation to their haemostatic capacity.

A comparison has been made between Defibrase and heparin during prolonged extracorporeal circulation with a membrane oxygenator in dogs. There was less capillary bleeding and less accumulation of platelets in lungs and on oxygenator membranes in defibrinogenated dogs. It was concluded that defibrinogenation is a superior anticoagulation alternative to heparinization under these experimental conditions.

Between May 1980 and February 1985, 30 patients were operated upon at Sahlgren's Hospital for life-threatening or disabling arrhythmias, caused by Kent's bundles. Two surgical methods were used. The outcome of surgery was fully satisfactory in 19 patients, whereas 4 patients continued to have arrhythmias after surgery. Six patients had a modified delta-wave in the ECG after surgery, but their arrhythmias could be controlled by antiarrhythmic medication. One patient died after surgery due to an undiagnosed cerebral tumor. There were 2 late deaths, between 6 and 12 months postoperatively; neither of these was caused by arrhythmias.

Blood or plasma with a known fibrinogen content was given to 2 groups of dogs defibrinogenated with an excess amount of DefibraseR. One group received a smaller volume corresponding to 0.05 g fibrinogen/kg bw and the other a larger volume corresponding to 0.08 g/kg bw during 1 hour. Circulation, lung and kidney functions were studied: coagulation and fibrinolysis variables were followed. The group receiving the smaller amount of fibrinogen did not show any adverse reactions. The other group showed decreasing arterial pO2, increased pulmonary artery pressure and decreased oxygen consumption. It is concluded that it is possible to give without adverse effects limited amounts of fibrinogen to dogs treated with an excess amount of DefibraseR.

Mongrel dogs were rapidly defibrinogenated with Defibrase R . During defibrinogenation, changes in the blood coagulation and fibrinolytic systems were followed and the circulatory, pulmonary and renal functions were studied. Besides the expected decrease in the fibrinogen concentration and an increase in fibrin(ogen) degradation products, there was a decreased cardiac output and right ventricular systolic pressure. The dogs were then given plasma intraarterially during one hour in a volume corresponding to 0.08 g fibrinogen/kg b.w. and the same recordings were repeated. The fibrinogen degradation products increased and there were measurable fibrin monomers in the plasma. While the pulmonary and renal functions remained unaffected, the cardiac output, right ventricular pressure, renal artery flow and central venous pressure were increased. It is concluded that plasma can be infused intra-arterially without disturbances in the renal and pulmonary function.

Ten consecutive patients aged 25 to 75 with postoperative empyema or hemothorax conventionally treated with drainage without sufficient effect were given intrapleural instillations of streptokinase (Kabikinase, 250,000 IE) for 4 hours). The effects on systemic fibrinolysis were studied. Venous blood samples for determination of fibrinolytic activity on fibrin plates, plasminogen, alpha 2-antiplasmin, alpha 2-macroglobulin, fibrinogen, fibrin(ogen) degradation products (FDP) and thrombin time were taken before instillation, after instillation and then after 24 hours. Preinstillation values were compared to the values 4 and 24 hours after instillation with Student's paired t-test. There were no differences in fibrinolytic activity, alpha 2-macroglobulin and thrombin time. There was a slight increase in plasminogen, alpha 2-antiplasmin and fibrinogen, probably due to an acute phase reaction. Fibrin degradation products showed an increase with border line significance. These changes are not consistent with generalized fibrinolysis, and it is concluded that intrapleural instillations of streptokinase can be given safely in the early posttraumatic or postoperative period.

Defibrase was used for anticoagulation in dogs during extracorporeal perfusion up to 6 hours with a Travenol membrane oxygenator or a Pall filter. The anticoagulation effect was adequate. The already low fibrinogen concentration became unmeasurable, the platelet count decreased, and the fibrin(ogen) degradation products increased during the perfusion. Histological examination showed platelets and white blood cells on the membranes. Perfusion pressure and blood flow were stable during the experiments, and no bleeding, thromboembolism or other adverse side-effects were noted. Defibrase might be an alternative to heparin for anti-coagulation during extra-corporeal circulation.

Four dogs were given heparin and four other dogs were defibrinogenated with Defibrase®. The dogs were then perfused for six hours with a membrane oxygenator. Capillary bleeding tendency was measured with a standardized skin-flap technique. Platelet accumulation in the lungs and on the oxygenator membranes was examined with 51Cr-labelled platelets and with scanning electron microscopy. Fibrin deposits on the oxygenator membranes were examined with immunoelectrophoresis after plasmic degradation. Pump flow, gas transfer across the oxygenator membrane and coagulation data were followed.Capillary bleeding from the skin-flap was more pronounced in the dogs treated with heparin than in the defibrinogenated dogs. The 51Cr-labelled platelets accumulated in the lungs and on the membranes of both groups, but more pronounced in the heparinized animals. Scanning electron microscopy confirmed the findings for oxygenator membranes. Both groups of animals had fibrin deposits on the membranes with wide individual variations. There was no difference between the two groups concerning gas exchange across the oxygenation membranes. The pump flow was higher in the defibrinogenated dogs (mean flow 38-64 ml/min and kg bw) than in the heparinized ones (mean flow 22-40 ml/min and kg bw).Anticoagulation with Defibrase® might be an alternative to heparin during prolonged extracorporeal perfusion.

Ischemic myocardial injury is the main cause for myocardial dysfunction after open-heart surgery and the main cause for ischemic damage is imbalance between energy demand and energy supply before, during, and after aortic cross clamping [1, 2]. The major steps taken to prevent myocardial injury are cooling and cardiac arrest. In patients with ischemic heart disease uneven distribution of cold cardioplegic solution will occur, resulting in impaired cooling of poststenotic areas, as shown by thermography [3]. Ischemia induces liberation of catecholamines from the nerve endings in the myocardium [4], which together with the raised sympathetic activity during cardiopulmonary bypass [5] increases the metabolic rate, with resulting energy depletion and increased ischemic damage. The energy supply during the ischemic period relies to a great extent on glycolysis or glycogenolysis.

A four-hour insulin "clamp" technique was used to study the dose-response relationship between a wide range of plasma concentrations of insulin (5.0-7000 mU/l), free fatty acids, adrenaline and noradrenaline in 28 patients directly after open heart surgery. The influence of beta-blockers is discussed. All patients had elevated levels of free fatty acids at the beginning of the study (1020 +/- 77 mumol/l). After 4 hours the decline in free fatty acids was significant in all insulin-treated patients and most pronounced in the groups with insulin concentrations of more than approximately 350 mU/l, i.e. when insulin was infused with 0.3 units/kg bw/hour or more. No significant decrease in free fatty acids was observed in the control group. Adrenaline and noradrenaline in plasma were markedly increased throughout the study and were unaffected by the insulin infusions in all groups.

Myocardial protection with cold cardioplegia has made it possible to prolong the time of aortic cross-clamping during open-heart surgery. Myocardial ischemia for up to 120 minutes is considered acceptable under these conditions. Eighty-seven patients operated upon for various heart lesions with cardiopulmonary bypass and aortic cross-clamping for more than 2 hours (mean time 146 minutes) were reviewed. Myocardial protection was achieved with cold cardioplegia, in some cases with additional topical cooling of the heart. Ten patients died and 77 were discharged from the hospital. Perioperative and early postoperative deaths could not be correlated to aortic cross-clamping time or the method of myocardial protection. Aortic cross-clamping can be safely performed for a period far longer than 2 hours with myocardial preservation by cold cardioplegia.

The splanchnic balance of glucose was studied in the basal state and at three levels of "clamped" hyperinsulinemia (260 +/- 23, 510 +/- 59, 3875 +/- 367 mU/liter) in 24 patients (43-70 years of age), who had undergone coronary surgery about 1 hr previously. The splanchnic balance of glucose in the basal state was negative in all patients (-1.6 +/- 0.3 mg/kg/min) and was changed into a zero-balance within 30 min when 0.15 or 0.3 U/kg/hr of insulin was infused. At an insulin infusion rate of 1.0 U/kg/hr the net splanchnic glucose balance was turned into a significant positive balance of an average 0.9 +/- 0.3 mg/kg/min.