Systemic nitric oxide clamping in normal humans guided by total peripheral resistance.

AIM: We wanted to stabilize the availability of nitric oxide (NO) at levels compatible with normal systemic haemodynamics to provide a model for studies of complex regulations in the absence of changes in NO levels. METHODS: Normal volunteers (23-28 years) were infused i.v. with the nitric oxide synthase (NOS) inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME) at 0.5 mg kg(-1) h(-1). One hour later, the NO donor sodium nitroprusside (SNP) was co-infused in doses eliminating the haemodynamic effects of l-NAME. Haemodynamic measurements included blood pressure (MABP) and cardiac output (CO) by impedance cardiography. RESULTS: l-NAME increased MABP and total peripheral resistance (TPR, 1.02 + or - 0.05 to 1.36 + or - 0.07 mmHg s mL(-1), mean + or - SEM, P < 0.001). With SNP, TPR fell to a stable value slightly below control (0.92 + or - 0.05 mmHg s mL(-1), P < 0.05). CO decreased with l-NAME (5.8 + or - 0.3 to 4.7 + or - 0.3 L min(-1), P < 0.01) and returned to control when SNP was added (6.0 + or - 0.3 L min(-1)). A decrease in plasma noradrenaline (42%, P < 0.01) during l-NAME administration was completely reversed by SNP. Plasma renin activity decreased during l-NAME administration and returned towards normal after addition of SNP. In contrast, plasma aldosterone was increased by l-NAME and remained elevated. CONCLUSIONS: Concomitant NOS inhibition and NO donor administration can be adjusted to maintain TPR at control level for hours. This approach may be useful in protocols in which stabilization of the peripheral supply of NO is required. However, the dissociation between renin and aldosterone secretion needs further investigation.

Prolonged prophylaxis with dalteparin to prevent late thromboembolic complications in patients undergoing major abdominal surgery: a multicenter randomized open-label study.

BACKGROUND: Patients undergoing major abdominal surgery carry a high risk of venous thromboembolism (VTE), but the optimal duration of postoperative thromboprophylaxis is unknown. OBJECTIVES: To evaluate the efficacy and safety of thromboprophylaxis with the low molecular weight heparin (dalteparin), administered for 28 days after major abdominal surgery compared to 7 days' treatment. PATIENTS/METHODS: A multicenter, prospective, assessor-blinded, open-label, randomized trial was performed in order to evaluate prolonged thromboprophylaxis after major abdominal surgery. In total, 590 patients were recruited, of whom 427 were randomized and received at least 1 day of study medication, and 343 reached an evaluable endpoint. The primary efficacy endpoint was objectively verified VTE occurring between 7 and 28 days after surgery. All patients underwent bilateral venography at day 28. RESULTS: The cumulative incidence of VTE was reduced from 16.3% with short-term thromboprophylaxis (29/178 patients) to 7.3% after prolonged thromboprophylaxis (12/165) (relative risk reduction 55%; 95% confidence interval 15-76; P=0.012). The number that needed to be treated to prevent one case of VTE was 12 (95% confidence interval 7-44). Bleeding events were not increased with prolonged compared with short-term thromboprophylaxis. CONCLUSIONS: Four-week administration of dalteparin, 5000 IU once daily, after major abdominal surgery significantly reduces the rate of VTE, without increasing the risk of bleeding, compared with 1 week of thromboprophylaxis.

Systematic review of thromboprophylaxis in colorectal surgery -- an update.

OBJECTIVE: The incidence of thromboembolism after colorectal surgery is higher than after general surgery. The aim of this paper is to update a systematic review addressing thrombosis prophylaxis in connection with colorectal surgery. METHODS: MEDLINE, EMBASE, LILACS, abstract books and reference lists from reviews were searched without language restrictions for randomized controlled trials or clinical controlled trials comparing prophylactic interventions and/or placebo up til August 2003. Five hundred and fifty-eight studies were identified of which 19 fulfilled the inclusion criteria. Data extraction was done by at least two of the authors. Outcome was deep venous thrombosis and/or pulmonary embolism diagnosed by various methods. RESULTS: Any kind of heparin is better than no treatment or placebo (11 studies) with a Peto Odds ratio (POR) at 0.32 (95% CI 0.20-0.53). Unfractionated heparin and low molecular weight heparin (4 studies) were equally effective POR 1.01 (95% CI 0.67-1.52). The combination of graduated compression stockings and LMWH is better than LMWH alone (2 studies) with a POR at 4.17 (95% CI 1.37-12.70). CONCLUSION: The optimal thromboprophylaxis in colorectal surgery is the combination of graduated compression stockings and low-dose unfractionated heparin or low molecular weight heparin.

Effects of oxytocin in normal man during low and high sodium diets.

AIM: We tested the hypothesis that oxytocin in normal man causes natriuresis by means of nitric oxide and/or atrial natriuretic peptide. METHODS: Normal male subjects were investigated after 4 days of sodium controlled diets (30 mmol sodium chloride day(-1), n = 8 or 230 mmol sodium chloride day(-1), n = 6). Oxytocin was infused intravenously (1 pmol kg(-1) min(-1) for 240 min). RESULTS: Mean arterial blood pressure, heart rate and glomerular filtration rate by clearance of chromium-labelled ethylenediaminetetraacetate remained stable. Plasma oxytocin increased from 2 to 3 pg mL(-1) to around 50 pg mL(-1). Oxytocin decreased urine flow (4.2 +/- 0.2--0.75 +/- 0.11 and 4.6 +/- 1.3-1.4 +/- 0.6 mL min(-1), low- and high-salt diet, respectively). During low-salt conditions, oxytocin reduced sodium and potassium excretion (11 +/- 2--4 +/- 2 and 93 +/- 19--42 +/- 3 micromol min(-1), respectively). Plasma renin, angiotensin II, aldosterone and renal excretion of metabolites of nitric oxide (nitrate and nitrite) all decreased. Plasma atrial natriuretic peptide and cyclic guanosine monophosphate were unchanged. A similar pattern was obtained during high-salt conditions but in this case the antinatriuresis was not different from that occurring during the corresponding time control series. CONCLUSIONS: The data reject the hypothesis. In contrast, we found significant antinatriuretic, antikaliuretic and antidiuretic effects, which were not mediated by the renin-angiotensin-aldosterone system, atrial natriuretic peptide, systemic haemodynamics, or processes increasing urinary excretion of metabolites of nitric oxide. The natriuretic effect of oxytocin found in laboratory animals is species-specific.

Heparins and mechanical methods for thromboprophylaxis in colorectal surgery.

BACKGROUND: Colorectal surgery implies higher risk of postoperative thromboembolic complications as deep venous thrombosis (DVT) and pulmonary embolism (PE) than general surgery. The best prophylaxis in general surgery is heparin and graded compression stockings. No systematic review on combination prophylaxis or on thrombosis prophylaxis in colorectal surgery has been published. OBJECTIVES: To compare the incidence of postoperative thromboembolism after colorectal surgery using prophylactic methods focussing on heparins and mechanical methods alone and in combinations. SEARCH STRATEGY: Electronic searches was performed in PUBMED, EMBASE, LILACS and the Cochrane Library. Abstract books from major congresses were handsearched as were reference lists from previously performed reviews. SELECTION CRITERIA: RCT or CCT comparing prophylactic interventions and/or placebo. Outcomes were ascending venography, 125 I-fibrinogen uptake test, ultrasound methods, pulmonary scintigraphy. Studies, using thermographic methods, other isotopic methods, plethysmographic methods, and purely clinical methods as the only diagnostic measure were excluded. 558 studies were identified - 477 were excluded. Only 3 of the identified studies focused exclusively on colorectal surgery. Studies of general surgery contain considerable numbers of colorectal patients. The authors of 66 studies in general and/or abdominal surgery were contacted for retrieving the results from the colorectal patients. Answers were received from very few. 19 studies entered this review. DATA COLLECTION AND ANALYSIS: All studies and all data extraction were performed by at least two of the authors. Outcome was deep venous thrombosis and/or pulmonary embolism. Analysis of bleeding complications were unfeasible. 12 meaningful outcomes were analysed by means of the fixed effects model with Peto Odds Ratios. MAIN RESULTS: Heparins versus no treatment: Any kind of heparincompared to no treatment or placebo (comparison 07.03, 11 studies). Heparin is better in preventing DVT and/or PE with a Peto Odds ratio at 0.32 (95% Confidence Interval 0.20-0.53) Unfractionated heparin versus low molecular weight heparin (comparison 08.03, 4 studies). The two treatments were found equally effective in preventing DVT and/or PE with a Peto Odds ratio 1.01 (95% Confidence Interval 0.67-1.52). Mechanical methods (comparison 10.3, 2 studies). The combination of graded compression stockings and LDH is better than LDH alone in preventing DVT and/or PE with a Peto Odds ratio at 4.17 (95% Confidence Interval 1.37-12.70). REVIEWER'S CONCLUSIONS: The optimal prophylaxis in colorectal surgery is the combination of graduated compression stockings and low-dose unfractionated heparin. The unfractionated heparin can be replaced with low molecular weight heparin.

Mechanisms of acute natriuresis in normal humans on low sodium diet.

This study evaluates the relative importance of several mechanisms possibly involved in the natriuresis elicited by slow sodium loading, i.e. the renin-angiotensin-aldosterone system (RAAS), mean arterial blood pressure (MAP), glomerular filtration rate (GFR), atrial natriuretic peptide (ANP), oxytocin and nitric oxide (NO). Eight seated subjects on standardised sodium intake (30 mmol NaCl day(-1)) received isotonic saline intravenously (NaLoading: 20 micromol Na(+) kg(-1) min(-1) or approximately 11 ml min(-1) for 240 min). NaLoading did not change MAP or GFR (by clearance of (51)Cr-EDTA). Significant natriuresis occurred within 1 h (from 9 +/- 3 to 13 +/- 2 micromol min(-1)). A 6-fold increase was found during the last hour of infusion as plasma renin activity, angiotensin II (ANGII) and aldosterone decreased markedly. Sodium excretion continued to increase after NaLoading. During NaLoading, plasma renin activity and ANGII were linearly related (R = 0.997) as were ANGII and aldosterone (R = 0.999). The slopes were 0.40 pM ANGII (mi.u. renin activity)(-1) and 22 pM aldosterone (pM ANGII)(-1). Plasma ANP and oxytocin remained unchanged, as did the urinary excretion rates of cGMP and NO metabolites (NO(x)). In conclusion, sodium excretion may increase 7-fold without changes in MAP, GFR, plasma ANP, plasma oxytocin, and cGMP- and NO(x) excretion, but concomitant with marked decreases in circulating RAAS components. The immediate renal response to sodium excess appears to be fading of ANGII-mediated tubular sodium reabsorption. Subsequently the decrease in aldosterone may become important.

Heparins and mechanical methods for thromboprophylaxis in colorectal surgery.

BACKGROUND: Colorectal surgery implies higher risk of postoperative thromboembolic complications as deep venous thrombosis (DVT) and pulmonary embolism (PE) than general surgery. The best prophylaxis in general surgery is heparin and graded compression stockings. No systematic review on combination prophylaxis or on thrombosis prophylaxis in colorectal surgery has been published. OBJECTIVES: To compare the incidence of postoperative thromboembolism after colorectal surgery using prophylactic methods focussing on heparins and mechanical methods alone and in combinations. SEARCH STRATEGY: Electronic searches was performed in MEDLINE, EMBASE back to 1970. Abstract books from major congresses were handsearched as were reference lists from previously performed reviews. SELECTION CRITERIA: RCT or CCT comparing prophylactic interventions and/or placebo. Outcomes were ascending venography, 125 I-fibrinogen uptake test, ultrasound methods, pulmonary scintigraphy. Studies, using thermographic methods, other isotopic methods, plethysmographic methods, and purely clinical methods as the only diagnostic measure were excluded. 558 studies were identified - 477 were excluded. Only 3 of the identified studies focused exclusively on colorectal surgery. Studies of general surgery contain considerable numbers of colorectal patients. The authors of 66 studies in general and/or abdominal surgery were contacted for retrieving the results from the colorectal patients. Answers were received from very few. 19 studies entered this review. DATA COLLECTION AND ANALYSIS: All studies and all data extraction were performed independently by at least two of the authors. Outcome was deep venous thrombosis and/or pulmonary embolism. Analysis of bleeding complications were unfeasible. 12 meaningful outcomes were analysed by means of the fixed effects model with Peto Odds Ratios. MAIN RESULTS: Heparins versus no treatment: Any kind of heparincompared to no treatment or placebo (comparison 07.03, 11 studies). Heparin is better in preventing DVT and/or PE with a Peto Odds ratio at 0.32 (95% Confidence Interval 0.20-0.53) Unfractionated heparin versus low molecular weight heparin (comparison 08.03, 4 studies). The two treatments were found equally effective in preventing DVT and/or PE with a Peto Odds ratio 1.01 (95% Confidence Interval 0.67-1.52). Mechanical methods (comparison 10.3, 2 studies). The combination of graded compression stockings and LDH is better than LDH alone in preventing DVT and/or PE with a Peto Odds ratio at 4.17 (95% Confidence Interval 1.37-12.70). REVIEWER'S CONCLUSIONS: The optimal prophylaxis in colorectal surgery is the combination of graduated compression stockings and low-dose unfractionated heparin. The unfractionated heparin can be replaced with low molecular weight heparin.

Survey of the use of thromboprophylaxis in laparoscopic surgery in Denmark.

BACKGROUND: The aim of this study was to determine the current use of thromboprophylaxis for laparoscopic surgery in Denmark. METHODS: Postal questionnaires were sent to all Danish surgical departments that performed laparoscopic surgery according to the National Laparoscopic Cholecystectomy Database. RESULTS: There was a written protocol for thromboprophylaxis in 93 per cent of the responding departments. In 37 per cent thromboprophylaxis was used for all patients undergoing laparoscopic surgery; only 7 per cent used thromboprophylaxis sporadically. All departments used low molecular weight heparin, 74 per cent in combination with graduated compression stockings. The criteria for using thromboprophylaxis varied greatly; in many departments conversion of the procedure to an open operation was not considered a criterion. Some 20 per cent of the departments reported previous thromboembolic complications following laparoscopic surgery. CONCLUSION: Despite the widespread use of thromboprophylaxis, symptomatic thromboembolic complications were reported from several departments. Further studies are needed to determine whether laparoscopic surgery should be considered a high-risk procedure.

Cysteines involved in the interconversion between dehydrogenase and oxidase forms of bovine xanthine oxidoreductase.

Mammalian xanthine oxidoreductase exists intracellularly in its dehydrogenase form. However, outside of this reducing milieu the enzyme quickly transforms into an oxidase form. Interconversion can be controlled by sulfhydryl reactive reagents, suggesting that disulfide bridging is linked to this phenomenon. The present work identified cysteines involved in the interconversion process. Purified enzyme was subjected to mild reduction with 1,4-dithioerythriol to regain dehydrogenase activity, and the accessible cysteines were labeled with specific radioactive alkylation reagents, iodoacetic acid. This partial alkylation stabilizes the dehydrogenase form, presumable by hindering formation of disulfide bond(s). Six of 38 cysteines were found to be labeled (residues 169, 170, 535, 992, 1317, and 1325). The significance of this labeling of bovine xanthine oxidoreductase is discussed in relation to structural knowledge about the enzyme, and especially by comparison with the AA sequences of avian and invertebrate enzymes, which do not undergo conversion. Cysteines 535 and 992 are the most likely marked residues to be involved in the interconversion, whereas the other cysteines are located too far from the cofactorbinding areas in xanthine oxidoreductase.

Assignment of disulfide bridges in bovine CD36.

The multifunctional membrane protein CD36 is expressed on platelets, mature monocytes and macrophages, microvascular endothelial cells and mammary epithelial cells. The exact physiological function of this glycoprotein is unclear. In order to determine the number and pattern of disulfide bridges, CD36 was purified from bovine milk fat globule membranes. The purification procedure involved Triton X-114 extraction, DEAE-Sepharose ion-exchange chromatography and reverse-phase chromatography on a Resource RPC column. The CD36 preparation was used for characterization of the disulfide bridge pattern, which was determined by peptide mapping, amino acid sequence analysis, and matrix-assisted laser-desorption ionization/time of flight mass spectrometry. We have found that there are no free cysteines in CD36 and that the six centrally clustered cysteines are linked by disulfide bonds, Cys242-Cys310, Cys271-Cys332 and Cys312-Cys321, resulting in a 1-3, 2-6 and 4-5 arrangement of the disulfide bridges. These data are in agreement with a model where the protein is oriented so that it has two short intracellular segments (residues 1-6 and 461-471) and two transmembrane domains (residues 7-28 and 439-460), and with four cysteines expected to be acylated placed near the intracellular side of the membrane. The remaining part of CD36 is extracellular, comprising eight glycosylations and three disulfide bridges. In the CD36 family of membrane proteins, it is likely that a similar pattern of disulfide bridges can be found in the sensory neuron membrane protein-1 from the silk moth Antheraea polyphemus and the mammalian scavenger receptor class B type I, whereas lysosome membrane protein II, and epithelial membrane protein from Drosophila melanogaster are both lacking one cysteine in the area of interest.

Incidence and prevention of deep venous thrombosis occurring late after general surgery: randomised controlled study of prolonged thromboprophylaxis.

OBJECTIVE: To study the incidence of late deep venous thrombosis (DVT), and to evaluate a regimen of prolonged thromboprophylaxis after general surgery. DESIGN: Randomised, controlled, open trial, with blinded evaluation. SETTING: University hospital, Denmark. SUBJECTS: 176 consecutive patients undergoing major elective abdominal or non-cardiac thoracic operations, of whom 118 were eligible for evaluation. INTERVENTIONS: Thromboprophylaxis with a low-molecular-weight heparin, tinzaparin, given for four weeks (n = 58), compared with one week (control group, n = 60). MAIN OUTCOME MEASURES: Presence of DVT established by bilateral venography four weeks after the operation. RESULTS: The incidence of late DVT in the control group was 6/60 (10%, 95% confidence interval (CI) 4% to 21%). In the prophylaxis group it was 3/58 (5.2%, 95% CI 1% to 14%) (p = 0.49). CONCLUSION: Prolonged thromboprophylaxis had no significant effect on the incidence of DVT occurring late after general surgery.

An ester bond linking a fragment of a serine proteinase to its serpin inhibitor.

Most known members of the serpin superfamily are serine proteinase inhibitors. Serpins are therefore important regulators of blood coagulation, complement activation, fibrinolysis, and turnover of extracellular matrix. Serpins form SDS-resistant complexes of 1:1 stoichiometry with their target proteinases by reaction of their P1-P1' peptide bond with the active site of the proteinases. The nature of the interactions responsible for the high stability of the complexes is a controversial issue. We subjected the complex between the serine proteinase urokinase-type plasminogen activator (uPA) and the serpin plasminogen activator inhibitor-1 (PAI-1) to proteolytic digestion under nondenaturing conditions. The complex could be degraded to a fragment containing two disulfide-linked peptides from uPA, one of which included the active site Ser, while PAI-1 was left undegraded. By further proteolytic digestion after denaturation and reduction, it was also possible to degrade the PAI-1 moiety, and we isolated a fragment containing 10 amino acids from uPA, encompassing the active site Ser, and 6 amino acids from PAI-1, including the P1 Arg. Characterization of the fragment gave results fully in agreement with the hypothesis that it contained an ester bond between the hydroxyl group of the active site Ser and the carboxyl group of the P1 Arg. These data for the first time provide direct evidence that serine proteinases are entrapped at an acyl intermediate stage in serine proteinase-serpin complexes.

Extracorporeal shock wave lithotripsy as first line monotherapy of solitary calyceal calculi.

Eighty-four patients with solitary calyceal stones were treated with Extracorporeal Shock Wave Lithotripsy (ESWL) as first line monotherapy. The indications for treatment were pain in 51 patients (61%), infection in 11 patients (13%), pain and infection in 18 patients (21%) and others in 4 patients (5%). Stone size (largest diameter) was median 9 mm (range 2-25 mm). Follow-up consisted of clinical control, isotope renography and a plain film after 1 month; hereafter plain films after 3 and 6 months. Auxiliary procedures due to steinstrasse were performed in 3 out of 4 patients (1 nephrostomy, 1 nephrostomy + ESWL of ureteral fragments, and 1 ureteroscopic manipulation). Retreatment of the calyceal stone was performed in 3 patients within 6 months (2 re-ESWL, 1 lower pole resection). Stone-free (without retreatment or auxiliary procedures) were 26/84 (31%) after 1 month, 34/84 (40%) after 3 months and 38/84 (45%) after 6 months. Free of pain were 43/69 (62%) after 1 month, 50/69 (72%) after 3 months and 59/69 (86%) after 6 months. Free of infection were 18/29 (62%) after 1 month, 19/29 (66%) after 3 months and 21/29 (72%) after 6 months. Complications included steinstrasse in 4 patients, sepsis in 3 patients, displacement of JJ-stent in 2 patients and atrio-ventricular dissociation in 1 patient. To conclude: ESWL as first line therapy for solitary calyceal calculi offers good results with regard to pain and clearance of infection, but leaves 55% with residual stone material.

Purification of the bovine xanthine oxidoreductase from milk fat globule membranes and cloning of complementary deoxyribonucleic acid.

The amino acid sequence of the bovine xanthine oxidoreductase was determined by cloning and sequencing cDNA clones encoding the enzyme. Partial amino acid sequence corresponding to 54% of the total sequence were also determined from purified bovine milk xanthine oxidoreductase, showing identity with the translated cDNA sequence. The cDNA of 4719 nucleotides included a 5' untranslated region of 96 nucleotides, an open reading frame encoding a xanthine oxidoreductase of 1332 amino acid residues, and a 3' untranslated region of 624 nucleotides including two polyadenylation signals and a poly (A) tail of 74 nucleotides. The identity between the amino acid sequence of the bovine xanthine oxidoreductase and xanthine oxidoreductase from mammalian species was 86 to 90%.

Colour Doppler flow imaging ultrasonography versus venography as screening method for asymptomatic postoperative deep venous thrombosis.

OBJECTIVE: To evaluate colour Doppler flow imaging ultrasonography (CDFI), compared with venography, as a screening method for postoperative deep venous thrombosis (DVT) in a clinical trial on thromboprophylaxis. METHODS: Patients undergoing major abdominal or thoracic surgery were prospectively screened for DVT by CDFI. Patients were examined preoperatively, and on post-operative days 1, 3, 7, 14, 21, and 28. When the CDFI was positive venography was performed. Bilateral venography was performed on day 28 in all patients. The study group comprised 82 patients who underwent CDFI and venography on the same day: four because of suspected DVT (positive CDFI), and 78 on day 28 according to protocol. RESULTS: DVT was detected by venography in seven patients, in three of whom CDFI was positive. CDFI was falsely positive in one case. There were two popliteal and five calf DVTs, of which CDFI detected one and two, respectively. The sensitivity of CDFI was 43%, the specificity 99%. The PVpos for CDFI was 75%, and the PVneg 96%. CONCLUSION: Due to low sensitivity, CDFI cannot stand alone as a screening method for asymptomatic postoperative DVT.

Synchronized inhibition of the phospholipid mediated autoactivation of factor XII in plasma by beta 2-glycoprotein I and anti-beta 2-glycoprotein I.

Lupus anticoagulants are a group of antibodies commonly found in patients with autoimmune diseases such as systemic lupus erythematosus. Lupus anticoagulants inhibit phospholipid dependent coagulation and may bind to negatively charged phospholipids. Recent studies have suggested an association between anti-beta 2-glycoprotein I and a lupus anticoagulant, whose activity is frequently dependent on the presence of beta 2-glycoprotein I. Based on these observations, the effect of anti-beta 2-glycoprotein I on the autoactivation of factor XII in plasma was investigated. Autoactivation initiated by the presence of negatively charged phospholipids, but not by sulfatide, was strongly inhibited by immunoaffinity purified anti-beta 2-glycoprotein I. The dose-response curve of anti-beta 2-glycoprotein I was identical with that of a precipitating antibody, showing no inhibition at low and high antibody dilutions and maximal inhibition at an intermediate dilution. At high antibody concentrations, an increased rate of factor XIIa activation was observed. This increase was of the same magnitude as the decreased rate observed in plasma supplemented with the same amount of beta 2-glycoprotein I as in the plasma itself. This confirms the inhibitory effect of beta 2-GP-I on the contact activation and shows that inhibition is effective on the autoactivation of factor XII in plasma. The inhibitory action of beta 2-glycoprotein I was independent of the inhibition caused by the anti-beta 2-glycoprotein I/beta 2 glycoprotein I complex suggesting a synchronized inhibition of factor XII autoactivation by beta 2-glycoprotein I and anti-beta 2-glycoprotein I. The inhibition caused by the antibody is suggested to be caused by a reduced availability of negatively charged phospholipids due to the binding of the anti-beta 2-GP-I/beta 2-GP-I complex. This complex may be a lupus anticoagulant.

Postoperative fatal pulmonary embolism in a general surgical department.

BACKGROUND: This retrospective study describes the cases of postoperative pulmonary embolism (PE) in a general surgical department during a 3-year period. METHODS: To analyze the cases of PE, all patient data from the hospital central registry of diagnoses, pulmonary ventilation/perfusion scintigraphies (V/P scans), and autopsy records from a hospital in Denmark for the 3-year period from August 1986 to August 1989 were reviewed. Antithrombotic prophylaxis was applied routinely according to standard instructions. A total of 2,049 emergency and 2,832 elective operations were performed. The PEs were verified by autopsy or perfusion/ventilation scintigraphy. RESULTS: Postoperative PE was verified in 30 patients, which is equivalent to an incidence of 0.6% (95% confidence limits: 0.4% to 0.8%). With correction for autopsy rate (65%) the incidence is estimated to be 1.0% (0.6% to 1.3%). The incidence of fatal PE was 0.4% (0.2% to 0.5%). Fatal PE was found in 8.6% (5.0% to 13.5%) of the patients who had an autopsy performed. The incidence of fatal postoperative PE among patients who received thromboprophylaxis was 3.5%, compared with 11.2% in patients who did not receive prophylaxis, P < 0.05. Pulmonary embolism occurred in 3 patients younger than 40 years, and in 12 patients who had undergone minor surgery. CONCLUSIONS: The results of this retrospective study suggest that the incidence of fatal PE is reduced by low-dose heparin prophylaxis, and that the risk of developing PE is not limited to patients subjected to major surgery or older than 40 years of age. It is concluded that the indications for antithrombotic prophylaxis should also include minor surgery and patients aged less than 40 years. A standard instruction is strongly recommended for thromboprophylaxis in surgery, especially when dealing with emergency surgery.

Dextran sulphate inhibits phospholipid and sulphatide mediated autoactivation of factor XII.

In normal plasma, high molecular mass dextran sulphate (DS500) induces formation of amidolytic activity towards the chromogenic substrate H-D-Pro-Phe-Arg-p-nitroanilide (S-2302) specific to factor XII and kallikrein. No amidolytic activity was formed when plasma deficient in prekallikrein was exposed to DS500. In contrast, factor XII amidolytic activity was formed upon exposure to sulphatide or acidic phospholipids. To assess whether DS500 interferes with the sulphatide and the acidic phospholipid in activating factor XII, plasma deficient in prekallikrein was incubated with phosphatidylinositol phosphate (PtdInsP) and sulphatide at the conditions necessary for activation with these surfaces and various concentrations of DS500. DS500 inhibited both the PtdInsP and the sulphatide-mediated autoactivation in an antithrombin III independent manner. Heparin also inhibited the PtdInsP mediated autoactivation but not that mediated by sulphatide. The heparin inhibition was due to enhancement of the antithrombin III activity, which could be partly blocked by preincubation of plasma with rabbit anti-human antithrombin III IgG.