A rare cause of hemosuccus pancreaticus diagnosed with endoscopic ultrasound.

INTRODUCTION: Hemosuccus pancreaticus (HP), hemorrhage from the papilla of Vater through the pancreatic duct (PD), is a rare cause of upper gastrointestinal bleeding. It may be caused by chronic pancreatitis, pseudoaneurism and pancreatic tumors. Only 2% of HP involves the hepatic arteries. Endoscopic ultrasound (EUS) may not only visualize the presence of HP, previously seen on computed tomography/magnetic resonance imaging (CT/MRI), but also reveal additional pathology. CASE REPORT: A 62-year-old man was admitted with severe intermittent gastrointestinal bleeding. He underwent gastroscopy, colonoscopy and capsule endoscopy without sign of bleeding. The patient had no previous history of pancreatitis or infection. On CT and MRI scan with angiography, an aneurism of the common hepatic artery (CHA) was found, with a dilatation of the main PD toward the tail of the pancreas, but no apparent source of bleeding. EUS was then performed, and could show a partial thrombosed aneurysm of a hepatica with a diameter of 5 cm. In addition, a narrow fistula between the hepatic artery and PD could be identified using power Doppler. The patient was subsequently operated, which revealed a thrombosed arteriosclerotic aneurysm in the CHA with fistula to the PD. CONCLUSION: To the best of our knowledge, this is the second reported case of a severe gastrointestinal bleeding due to a fistula between the CHA and PD. The use of EUS in diagnosing this rare condition has not been reported before, but seems feasible.

Autotransfusion in coronary artery bypass grafting: disparity in laboratory tests and clinical performance.

OBJECTIVE: Autotransfusion during and after cardiac surgery is widely performed, but its effects on coagulation, fibrinolysis, and inflammatory response have not been known in detail. METHODS: Hemostatic and inflammatory markers were extensively studied in 40 coronary artery bypass patients undergoing a consistent intraoperative and postoperative autotransfusion protocol. An identical autotransfusion protocol was applied to 4916 consecutive coronary patients and the overall clinical results were evaluated in this large patient population. RESULTS: The autologous blood pooled before bypass remained nearly inactivated after storage. A slight elevation of thrombin-antithrombin complex and prothrombin fragment 1.2, as well as plasmin/alpha(2)-antiplasmin complex was found in the content of the extracorporeal circuit after surgery, indicating thrombin formation and fibrinolytic activity. Also some increase of beta-thromboglobulin was present. In the mediastinal shed blood, complete coagulation, as evidenced by the absence of fibrinogen, had taken place and all parameters described above were extremely elevated. However, no thrombin activity was detected. As for the inflammatory response, moderately increased levels of complement activation products, terminal complement complex, and interleukin-6 traced in the extracorporeal circuit reached very high levels in mediastinal shed blood. Autotransfusion of the residual extracorporeal circuit blood and the mediastinal drainage was followed by elevation of most of these markers in circulating plasma. On the other hand, no correlating harmful effects were recorded in the study patients or in the consecutive 4916 patients. Coagulation disturbances were rare and allogeneic transfusions were required in fewer than 4% of all patients. CONCLUSIONS: The hemostatic and immunologic systems were moderately activated in the autologous blood remaining in the extracorporeal circuit, whereas the mediastinal shed blood was highly activated in all aspects. However, autotransfusion had no correlating clinical side-effects and the subsequent exposure to allogeneic blood products was minimal.

Leucocyte filtration during cardiopulmonary reperfusion in coronary artery bypass surgery.

Postoperative organ dysfunction after cardiac operations has been related to the damaging effects of cardiopulmonary bypass (CPB). These complications are considered to be mediated partly by complement activation and subsequent activation of leucocytes due to the contact between blood and the large nonendothelial surfaces in the bypass circuit. Removal of leucocytes by filtration during the reperfusion period may potentially reduce the postoperative morbidity after CPB. Forty patients undergoing elective, primary coronary artery bypass grafting were randomized to initial identical bypass circuits until the aortic crossclamp was released. Then, the ordinary arterial line filter was closed and either a leucocyte depletion filter (n = 20), or a control filter (n = 20) was incorporated in the circuits during the reperfusion period of CPB. Blood samples were drawn at fixed intervals and analysed for white blood cell and platelet counts, plasma concentration of myeloperoxidase, C3-complement activation products, the terminal complement complex, and interleukins (IL)-6 and -8. The numbers of circulating white blood cells in the leucocyte-depleted group decreased during the reperfusion period from 5.5 (4.8-6.8) to 5.3 (4.4-6.2) x 10(9)/l, and increased in the control group from 6.5 (5.1-8.0) to 7.4 (5.7-9.0) x 10(9)/l. Two hours postoperatively the total white blood cell count in the leucocyte-depleted group was 14.7 (12.1-17.2) x 10(9)/l, and in the control group 17.6 (14.5-20.7) x 10(9)/l. The differences between the groups were statistical significant (p = 0.05). There were no statistically significant differences between the groups with regard to other test parameters or clinical data. We conclude that the use of leucocyte filters during the reperfusion period in elective coronary artery bypass surgery significantly reduced the number of circulating leucocytes, whereas no effects were seen for granulocyte activation measured as myeloperoxidase release, platelet counts, complement activation, or IL-6 and -8 release. The clinical benefit of leucocyte filters in routine or high risk patients remains to be demonstrated and is suggested to be dependent on both the efficacy and the biocompatibility of the filters.

Assessment of heparin anticoagulation: comparison of two commercially available methods.

BACKGROUND: The activated clotting time is a bedside method routinely used to monitor heparin anticoagulation during operations requiring cardiopulmonary bypass. The thrombolytic assessment system heparin management test is a new bedside method for monitoring heparin effect. We compared these methods with respect to their ability to reflect the actual heparin concentration in plasma determined by an anti-FXa method. METHODS: Two studies were done, an ex vivo study on ten patients who had coronary artery bypass using non-heparin-coated cardiopulmonary bypass circuits and full systemic heparinization and an in vitro study on single donor plasma spiked with heparin 0 to 10 IU/mL. RESULTS: Ex vivo study correlation coefficients of activated clotting time and the thrombolytic assessment system heparin management test clotting times versus anti-FXa-based heparin assay were low (r = 0.53, p = 0.002/r = 0.64, p<0.001) in contrast with the corresponding correlation coefficients for the in vitro study (r = 0.98, p<0.001/r = 0.99, p<0.001). A substantial variability in duplicate activated clotting time determinations was noted, which was less pronounced with the thrombolytic assessment system heparin management test. CONCLUSIONS: The thrombolytic assessment system method does not correlate better to the actual amount of heparin during cardiopulmonary bypass procedures than the activated clotting time method, which should be performed in duplicate.

Haemostatic parameters related to lipids and adhesion molecules.

Several components of blood, e.g. lipids, coagulation and fibrinolytic factors, are thought to be important risk factors in cardiovascular diseases. The aim of this study was to correlate these risk factors and the soluble adhesion proteins, soluble P-selection (sP-selectin) and soluble vascular cell adhesion molecule (sVCAM-1), in healthy men and women as well as to unravel any effects of smoking. One hundred and forty-two fasting men (median age 36 years) including 39 smokers, and 124 women (median age 34 years) including 35 smokers, were tested between 0800 h and 1000 h. Fibrinogen correlated positively with white blood cells (WBC) (r = 0.25), prothrombin fragment 1.2 (F1.2) (r = 0.21), cholesterol (r = 0.27), beta-thromboglobulin (r = 0.29), Factor VII clotting activity (FVIIc) (r = 0.27) (all P < 0.0001), tissue plasminogen activator antigen (t-PAag) (r = 0.22, P < 0.0005), plasminogen activator inhibitor-1 antigen (PAI-1ag) (r= 0.20) and VCAM-1 (r= 0.19) (both P< 0.002). Cholesterol and triacylglycerol (TG) correlated positively with t-PA antigen (t-PAag) (r = 0.36 and r = 0.38), PAI-1 antigen (PAI-1ag) (r = 0.35 and r = 0.50), P-selectin (r = 0.26 and r = 0.27) (all P < 0.0001) and WBC (r = 0.17, P < 0.007 and r = 0.18, P < 0.004). Cholesterol correlated also with F1.2 (r = 0.29) and TG (r= 0.44) (P< 0.0001). In addition to cholesterol and TG, sP-selectin correlated postively with PAI-1ag (r= 0.39), t-PAag (r= 0.27) and WBC (r = 0.25) (all P < 0.0001). Comparing the various test parameters in men and women, it was found that women had significantly higher levels of F 1.2 and high-density lipoprotein-cholesterol than men, whereas men had higher levels of t-PAag, PAI-lag and P-selectin than women. Smoking was associated with a rise in several of the test parameters. It can be concluded that there are correlations between several risk factors. Of particular interest is the positive correlation between sP-selectin and a number of established risk factors of cardiovascular diseases.

Effect of marine oils supplementation on coagulation and cellular activation in whole blood.

A study was performed to explore the effects of supplemental intake of various marine oils known to be part of the Eskimo diet. Healthy men and women (134) were randomly selected to consume 15 mL/d of oil from blubber of seal, cod liver, seal/cod liver, blubber of Minke whale, or no oil for ten weeks. Total cholesterol was unchanged in the oil groups, whereas high density lipoprotein cholesterol increased 7% in the seal/cod liver oil (CLO) group (P < 0.05) and 11% in the whale oil group (P < 0.005). Triacylglycerol was significantly reduced in the CLO group only. The concentration of prothrombin fragment 1 + 2 was reduced 25% (P < 0.05) after whale oil supplementation. No change in fibrinogen or factor VIIc was detected. Tumor necrosis factor generation in lipopolysaccharide (LPS)-stimulated blood was 30% reduced after whale oil (P < 0.05), but was unaffected by intake of seal or CLO. The LPS-induced tissue factor activity in monocytes was reduced to a significant degree only in the seal/CLO group (34%) and whale oil group (35%) (P < 0.05). The most dramatic change in thromboxane B2 in LPS-stimulated blood was seen after whale oil intake with 44% reduction (P < 0.01). Supplementation of a regular diet with a combination of seal oil and CLO and especially with whale oil seems to have beneficial effects on several products thought to be associated with cardiovascular and thrombotic diseases.

Granulocytes enhance LPS-induced tissue factor activity in monocytes via an interaction with platelets.

In the present study we have investigated the effect of platelets and granulocytes on bacterial lipopolysaccharide (LPS)-induced tissue factor (TF) activity in monocytes. Experiments were performed on freshly isolated cells resuspended in heparinized plasma and recombined with platelet-poor or platelet-rich plasma. In a platelet-dependent reaction the granulocytes enhanced LPS-induced TF activity by an average of 100%. The effect was dose dependent with regard to the number of both granulocytes and platelets, respectively. Granulocytes and/or platelets did not affect LPS-induced tumor necrosis factor (TNF) secretion from monocytes. Phorbol myristate acetate (PMA) per se was not able to induce TF activity in our system. In contrast, the agonist caused a substantial increase in TF activity induced by LPS. The effect was totally dependent on the presence of platelets and was shown to be due to stimulation of both granulocytes and monocytes (the activity rose from 30 +/- 7 to 83 +/- 12 mU/10(6) cells in the presence of platelets and from 69 +/- 8 to 143 +/- 22 mU/10(6) cells in the presence of platelets and granulocytes). Effects similar to those observed with PMA were obtained with physiological concentrations (10 ng/ml) of TNF. A combination of these two agonists gave no further amplification of LPS-induced TF activity compared with the effect of the agonists separately. Low concentrations of a monoclonal anti-CD15 antibody abolished the stimulatory effects of platelets and granulocytes. Furthermore, the anti-CD15 antibody neutralized the effect of TNF, whereas the PMA effect was reduced by almost 75%. These results were confirmed in a whole-blood system. The inhibitory effect of the antibody may be associated with CD15's role as a complementary ligand for PADGEM. Our study indicates that a close interaction between granulocytes, platelets, and monocytes is essential for optimal TF activity induced by LPS. It is hypothesized that the effect of granulocytes is related to their ability to activate platelets. We propose that upon activation granulocytes secrete a product that enhances the capacity of platelets to stimulate TF activity in monocytes.

Human leukocyte elastase and cathepsin G inactivate factor VII by limited proteolysis.

The effect of supernatant from phorbol myristate acetate (PMA) stimulated human polymorphonuclear granulocytes (PMN) on human factor VII was studied in vitro. The supernatant caused a rapid loss in factor VII coagulant activity by the action of human leukocyte elastase (HLE) and cathepsin G in the supernatant, as demonstrated by the use of specific inhibitors of the two serine proteases, respectively. Preincubation of the supernatant with the elastase inhibitor and the cathepsin G inhibitor preserved 80% and 25% of the clotting activity, respectively. Calcium protected factor VII completely from the supernatant mediated inactivation. Cathepsin G and HLE purified from PMN each destroyed the coagulant activity of factor VII when added to a non-plasma system. There were, however, no effect on factor VII activity when cathepsin G was added to plasma. Polyacrylamide gel electrophoresis in the presence of SDS indicated that HLE and cathepsin G cleaved the zymogen in the same manner, producing (a) peptide(s) of low molecular mass and a single large product of 48 kDa. Preincubation of factor VII with calcium ions inhibited the proteolytic action of HLE and cathepsin G. It is suggested that HLE and cathepsin G from activated granulocytes may be partly responsible for the loss in factor VII activity that is observed during sepsis.

Bacillus subtilis 168 genetic transformation mediated by outgrowing spores: necessity for cell contact.

Transforming activity released in sequential genetic order during the first synchronous cycle of DNA replication during outgrowth of spores of Bacillus subtilis 168 was investigated. A transformation assay was used consisting of outgrowing spores as DNA donors and multiply marked competent cells as recipients. DNA synthesis inhibitors known to stop DNA release were used during and subsequent to DNA transfer to recipient cells. The released DNA sedimented with the outgrowing cells after low-speed centrifugation, and it was discovered that markers released both early and late were resistant to up to 500 microgram of deoxyribonuclease per ml under conditions in which the transforming capacity of purified DNA was eliminated by 5 microgram of the nuclease per ml. Inaccessibility to deoxyribonuclease was increased and maintained during the transformation event while detergents and proteolytic attack did not expose the released chromosome to nuclease action. The results indicate that tight physical contact between outgrowing spores and competent cells is required for transformation in this system.