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O Thorlacius-Ussing

Publications and source records attributed to O Thorlacius-Ussing.

At least 19 recordsLinked to original sources
PubMed2003

Complement activation in plasma before and after infliximab treatment in Crohn disease.

BACKGROUND: Crohn disease is characterized by up-regulated intestinal inflammation mainly caused by increased tumour necrosis factor alpha (TNF-alpha) levels. However, the complement system (C) may also have a role in maintaining inflammation. METHODS: Plasma from 26 patients with Crohn disease complicated by fistulizing ano-rectal disease was collected before and after three Infliximab infusions (5 mg kg(-1)). RESULTS: Before treatment, the C3-activation capacities (C3-AC) in plasma from patients with Crohn disease were comparable with values obtained from healthy controls. The classical C pathway-mediated C3-AC, mannan-binding lectin C4-AC, leucocyte count, C-reactive protein concentration and Crohn Disease Activity Index decreased significantly 8 weeks after the first infusion of Infliximab (P < 0.04, Wilcoxon test). CONCLUSIONS: Before treatment, all three C pathways were within the normal range in plasma from patients with Crohn disease; the decrease observed in the classical pathway-mediated C3-AC after treatment with Infliximab reflects a general down-regulation in immune activation.

Adolescent↗
PubMed2002

Complement activation mediated by mannan-binding lectin in plasma from healthy individuals and from patients with SLE, Crohn's disease and colorectal cancer. Suppressed activation by SLE plasma.

We have developed a method for quantitating mannan-binding lectin (MBL)-induced activation of the complement system (MBL-C4-AC) in human plasma. This method and an assay for MBL concentration were applied to plasma samples from healthy individuals and patients with systemic lupus erythematosus (SLE), Crohn's disease (CD) and colorectal cancer (CRC). The MBL concentration was measured by an enzyme-linked immunosorbent assay (ELISA) using monoclonal anti-MBL-antibodies and MBL-C4-AC by an ELISA using solid-phase mannan, incubating with plasma samples and quantitating the complement (C) activation by the use of antibodies against the C split-products C4b/C4c. The MBL concentration was nonsignificantly elevated in plasma from SLE-patients, whereas MBL-C4-AC was suppressed (P < 0.04). There was no correlation between MBL concentration and MBL-C4-AC in plasma from SLE-patients. In contrast, a significant correlation was found between the MBL concentration and MBL-C4-AC in plasma from healthy individuals. The C4 concentration was significantly reduced (P < 0.002) in plasma from the SLE patients and showed a significant correlation to MBL-C4-AC. The MBL-C4-AC assay was highly effective in discriminating the SLE patients from the other patient groups and healthy individuals.

Adult↗
PubMed2002

Relationship of coagulation test abnormalities to tumour burden and postoperative DVT in resected colorectal cancer.

In a prospective study, coagulation test results were compared in 137 patients with colorectal cancer (CRC) and 39 subjects with benign colorectal diseases. Prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), and soluble fibrin (SF) were measured in plasma before and after surgery. CRC patients presented with significantly higher values of F1+2 and TAT than controls. Patients with localised CRC had elevated values of F1+2 and TAT, whereas patients with advanced CRC also had elevated SF values. TAT and SF levels correlated with tumour spread, and normal values virtually excluded advanced cancer. Postoperative deep venous thrombosis (DVT) was diagnosed by phlebography in 20% of the CRC patients. Preoperative values of the markers did not predict postoperative DVT, but postoperative values did.

Adult↗
PubMed2001

ELISA for evaluating the incorporation of plasma derived complement split-products C3b/iC3b into solid-phase immune complexes.

An ELISA that measures plasma derived complement (C) split-products C3b/iC3b deposited on solid-phase immune complexes during C activation is described. Plates are coated with BSA, anti-BSA and plasma is added. Deposited C3b/iC3b is then detected by biotinylated anti-C3c-antibodies, avidin-alkaline phosphatase and para-nitrophenylphosphate. A novel feature is that the assay measures residual C activation capacity rather than in vivo generated C activation products. The assay was applied to plasma from 250 healthy blood donors. No difference in activation capacity of either the alternative (AP) or classical pathway (CP) with regard to age or gender was demonstrated. The total coefficient of variation was <5.7%. The ELISA procedure was compared to a standard hemolytic complement CH(50) assay using plasma from 23 out-patients with systemic lupus erythematosus (SLE). There was a weak correlation between the two assays for both C pathways, but neither the ELISA nor the CH(50) assay showed any correlation with the diagnostic ACR-criteria for SLE. However, the capacity of the CP was significantly reduced in SLE out-patients compared to healthy blood donors (P<0.0001).

Antigen-Antibody Complex↗
PubMed1999

Plasma urokinase receptor levels in patients with colorectal cancer: relationship to prognosis.

BACKGROUND: The proteolytic enzyme plasmin, which is generated from the precursor plasminogen by the action of urokinase plasminogen activator, is thought to play a role in tumor cell invasion and metastasis. Urokinase plasminogen activator receptor (uPAR) is functionally involved in the cell surface activation (i.e., cleavage) of plasminogen. Increased tumor tissue levels of uPAR are associated with poor prognosis in several types of cancer. This retrospective study was undertaken to test the relationship between preoperative plasma levels of soluble uPAR (suPAR) and survival in patients with colorectal cancer. METHODS: suPAR levels in preoperative plasma from 591 patients with colorectal cancer were determined by use of a kinetic enzyme-linked immunosorbent assay and analyzed with respect to associations with postoperative survival, Dukes' stage, age, and serum carcinoembryonic antigen level. Plasma suPAR measurements were log transformed for survival analysis, which employed the Kaplan-Meier method and the Cox proportional hazards model. All P values reported are two-sided. RESULTS: Univariate analysis, using the log-transformed suPAR concentrations, demonstrated that there was an increasing risk of mortality with increasing plasma suPAR level (P<.0001). An arbitrary cut point, the median for all patients (1.37 ng/mL), divided patients with Dukes' stage B, C, or D disease into statistically different prognostic groups. In multivariate Cox analysis including Dukes' stage, age, and carcinoembryonic antigen level, the suPAR concentration independently predicted survival (P<.0001). CONCLUSIONS: The preoperative plasma suPAR level independently predicted survival of patients with colorectal cancer. Further studies of plasma suPAR in patients with cancer are needed to evaluate the utility of plasma suPAR measurements and cut points in identifying high-risk patients among those with early stage disease.

Adult↗
PubMed1999

Coagulation and fibrinolysis during laparoscopic cholecystectomy.

Laparoscopic surgery appears to be less traumatic to the patient than open surgery, but its influence upon coagulation and fibrinolysis is incompletely elucidated. Our aim was to measure markers of coagulation and fibrinolysis before, during. and after laparoscopic cholecystectomy (LC). Blood samples drawn on admission, on four occasions during operation as well as 2 hours after operation and on the first postoperative day in 50 patients undergoing elective LC were analyzed for prothrombin fragment 1+2 (F1+2), soluble fibrin (SF), D-dimer (DD), fibrin degradation products (FbDP), tissue-type plasminogen activator (tPA) activity and antigen, and plasminogen activator inhibitor (PAI) activity and antigen. F1+2, SF, DD, and FbDP levels increased significantly after LC. Differences between pre- and postoperative PAI and tPA levels were not significant apart from a transient increase in tPA antigen levels. tPA activity was significantly increased during operation.

Adult↗
PubMed1999

Systemic coagulation activation and anastomotic leakage after colorectal cancer surgery.

PURPOSE: The aim of the present study was to study whether patients developing anastomotic leakage after colorectal resections for colorectal cancer have laboratory signs of an altered hemostatic balance in the systemic circulation, preoperatively and postoperatively, causing an impaired healing process. METHODS: Patients operated on for colorectal cancer were studied. Seventeen consecutive patients with anastomotic leakage and 17 patients without anastomotic leakage were matched according to age, gender, tumor stage, and localization of tumor. Hemostatic balance was estimated preoperatively and at one, two, and seven days and at three months after surgery by plasma levels of sensitive markers of coagulation activation and fibrinolysis, i.e., prothrombin fragment 1 + 2, thrombin-antithrombin complexes, soluble fibrin, tissue-type plasminogen activator activity, and plasminogen activator inhibitor Type 1. RESULTS: Preoperatively, the hemostatic balance was comparable in patients with and without anastomotic leakage. In the early postoperative period, patients developing anastomotic leakage exhibited signs of systemic coagulation activation, i.e., elevated plasma levels of prothrombin fragment 1 + 2, thrombin-antithrombin complexes, soluble fibrin, and plasminogen activator inhibitor Type 1. The observed coagulation activation appeared before the anastomotic leakage became clinically evident. More patients with anastomotic leakage received perioperative blood transfusions than patients without leakage, despite the fact that duration of surgery and intraoperative blood loss were comparable in the two groups. CONCLUSIONS: Enhanced coagulation activity was observed postoperatively in patients developing anastomotic leakage after colorectal resections for colorectal cancer. Such a hypercoagulable state may contribute to the development of anastomotic leakage by facilitating formation of microthromboses in the perianastomotic area.

Age Factors↗
PubMed1999

The urokinase plasminogen activator receptor in blood from healthy individuals and patients with cancer.

The cell surface plasminogen activation system functions in promoting tumor dissemination, and is facilitated by a glycolipid anchored three domain receptor for urokinase. This receptor can also be found in a soluble form (suPAR) in extracts of tumors, as well as in plasma from both healthy individuals and cancer patients. The suPAR in plasma consists of the intact three domain protein, but neither the precise mechanism of its release from cell surfaces, nor its biological function are understood. Increased levels of plasma suPAR have been found in patients with cancers of the lung, breast, ovary, and colon, and recent data now indicates that the level of the molecule is related to patient prognosis.

Animals↗
PubMed1998

[New prognostic markers in colorectal cancer].

The majority of patients diagnosed as having colorectal cancer do not survive five years, although 70%-80% undergo curative surgery. Only a minority of the patients receive additional adjuvant chemo-, radio- and/or immunotherapy, which has proven its efficiency in a minor part of patients with Dukes C disease. Therefore, adjuvant therapy has only an insignificant impact on overall survival improvement. The present treatment of patients with colorectal cancer is far from sufficient, and this has led to considerations of how to optimize both surgical and adjuvant medical treatment strategy. Current biotechnological research in tumour biology has led to the development of several new treatment modalities, and within few years some of these will be tested clinically. It cannot be expected that all modalities may prove equally efficient in all patients. Furthermore, half the operated patients are cured by surgery alone, and these should not receive additional adjuvant treatment. Therefore, considerations are required of how to implement new modalities, and of selection of patients who are expected to benefit from a specific modality or a combination of modalities. It is suggested, that new biological markers of development, growth and dissemination of colorectal cancer can be used to predict prognosis either alone or in various combinations, and as selection markers to discriminate between patients who only need surgery and patients who may need adjuvant treatment.

Animals↗
PubMed1998

The effect of ranitidine on postoperative infectious complications following emergency colorectal surgery: a randomized, placebo-controlled, double-blind trial.

OBJECTIVE AND DESIGN: To study the potential effect of ranitidine on postoperative infectious complications following emergency colorectal surgery. A randomized, placebo-controlled, double-blind trial was carried out in three university clinics and two county hospitals in Denmark. PATIENTS AND TREATMENT: One hundred and ninety-four consecutive patients undergoing acute colorectal surgery for perforated and/or obstructed large bowel were randomized in a double-blind fashion to receive ranitidine 100 mg i.v. twice a day commencing at induction of anesthesia and continued for five days (group I) or i.v. placebo (group II). All patients were given 1.5 g metronidazole plus 3.0 g cefuroxime at the time of surgery. Patients with perforation of the colon or rectum were given metronidazole and cefuroxime for further 3 days. All patients were assessed daily until discharge from the hospital. Thirty patients were withdrawn from the study (for reasons such as other diagnosis, refused to continue, medication not given as prescribed). MAIN OUTCOME MEASURES: Patients were observed for signs of infectious complications; such as wound infection, intra-abdominal abscess, septicemia, and pneumonia. RESULTS: Both groups were similar with respect to age, sex, weight, duration of surgery, blood transfusions, and site of the procedure, as well as the histologic nature of the underlying disease process. However, the Mannheim Peritonitis Index (MPI) was significantly higher in group I compared with group II (p < 0.05). Wound infection, intraabdominal abscess, septicemia, and pneumonia were 12.9%, 5.2%, 3.8% and 14%, respectively in group I. In group II, the infectious complications were 16.1%, 6.8%, 6.9% and 22%, respectively. Twelve patients (13.8%) in the placebo group developed more than one complication compared with 5 patients (6.5%) in the ranitidine group. CONCLUSION: Ranitidine may have a beneficial effect on postoperative infectious complications in patients following acute colorectal surgery.

Adolescent↗
PubMed1996

Markers of fibrin formation in colorectal surgery: fibrinopeptide A and soluble fibrin.

Two markers of fibrin formation, fibrinopeptide A (FpA) and soluble fibrin (SF), were studied in order to elucidate whether they reflected intravascular fibrin formation in the same manner. Plasma was collected for measurements of FpA and SF in 34 patients during the course of colorectal surgery. Although both parametres reflected haemostatic activation postoperatively, covariation was neither observed preoperatively, nor on the second, third, and eighth postoperative days. At 3 months following surgery, however, FpA and SF was correlated. At that time, the activation of the coagulation system has ceased. The present results demonstrate a lack of correlation between these markers of fibrin formation during clotting activation. Quite different properties of the FpA and the SF molecules, different clearance rates and distribution volumes may explain the lack of correlation observed.

Adult↗
PubMed1996

Short-time stability of markers of coagulation and fibrinolysis in frozen plasma.

We studied the stability of three markers of coagulation (prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III complexes (TAT), and soluble fibrin (SF)) in stored frozen plasma, in addition to one marker of fibrinolysis (total fibrinogen degradation products and fibrin degradation products (TDP)). All markers were measured using enzyme linked immunosorbent assays (ELISA). None of the markers changed significantly after initial freezing. F1 + 2 in plasma was stable following storage at -80 degrees C for 3 months. In plasma containing high SF levels stored at -80 degrees C, an insignificant time dependent trend towards decreasing plasma values was observed. TAT levels in plasma decreased significantly following 3 months at -80 degrees C. TDP levels in plasma showed some fluctuation when stored in freezer. Our results suggest that careful observation of the long time storage stability of protein components is demanded in clinical research.

Adult↗
PubMed1996

Fibrin and fibrinogen degradation products in plasma of patients with colorectal adenocarcinoma.

PURPOSE: The aim of the present study was to correlate the preoperative plasma levels of TDP in patients with colorectal cancer to tumor stage, metastasis, and postoperative thromboembolic complications. METHODS: Ninety-one patients with colorectal cancer, 20 patients with colorectal adenoma, and 71 patients without neoplastic lesions in the colon or rectum were included in this prospective study. Before surgery, total fibrin and fibrinogen degradation products (TDP) were measured in plasma of all patients with a specific enzyme-linked immunosorbent assay test. Phlebography was performed postoperatively in 82 of 91 patients with colorectal cancer. RESULTS: Median TDP in plasma of patients with colorectal cancer (805 (range, 339-5,024) ng fibrinogen equivalents (ngFE)) was significantly higher than TDP in patients with colorectal adenoma (591 (range, 417-1386) ngFE/ml) and TDP in patients without neoplastic lesions in the colon (632.8 (range, 180-2622) ngFE/ml; P < or = 0.003). In patients with colorectal cancer and liver metastasis, TDP in plasma (1085.5 (range, 468-5024) ngFE/ml) was significantly higher than in patients with localized tumor growth (753 (range, (339-2,780) ngFE/ml; P < or = 0.02). Twenty of 82 patients (24 percent) with cancer developed thromboembolic complications. TDP was preoperatively significantly higher in this group of patients (1,101 (range, 468-2,167) ngFE/ml) compared with patients without thromboembolic complications (753 (range, 339-5024) ngFE/ml; P < or = 0.04). CONCLUSION: Preoperative plasma levels of TDP were elevated in patients with colorectal cancer, especially in patients with liver metastasis and in patients developing postoperative deep venous thrombosis.

Adenocarcinoma↗
PubMed1996

Pre- and postoperative state of coagulation and fibrinolysis in plasma of patients with benign and malignant colorectal disease--a preliminary study.

This study was carried out in order to compare the coagulation balance in patients with colorectal cancer before and after surgical removal of tumor with an age matched non-malignancy control group. Furthermore, it was studied whether preoperative coagulation state in cancer patients was correlated to the postoperative development of deep venous thrombosis (DVT) diagnosed by venography. Plasma was collected preoperatively in 93 cancer patients and 30 controls, and postoperatively on day one, two, seven, and ninety in 88 cancer patients and 18 controls. Prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin complex (TAT), and total fibrin(ogen) degradation products (TDP) were quantitated in plasma by enzyme linked immunosorbent assays (ELISA). As compared to controls, patients admitted for cancer treatment displayed significantly higher levels of F1 + 2 and TAT. Patients suffering from advanced colorectal cancer had significantly higher levels of TAT and TDP as compared to patients with localized colorectal cancer. Twenty-three percent of cancer patients developed DVT postoperatively. Preoperatively these patients displayed significantly higher TDP levels, and postoperatively higher levels of F1 + 2, TAT, and TDP compared to cancer patients without DVT. The marked activation of blood coagulation and fibrinolysis observed in all patients following major abdominal surgery was even more pronounced in patients not cured for cancer.

Adult↗
PubMed1995

Soluble fibrin in plasma before and after surgery for benign and malignant colorectal disease.

In a prospective study, plasma levels of soluble fibrin (SF) were assessed in 97 patients with colorectal cancer immediately before and 1, 2, 7, and 90 days after surgery, 18 patients undergoing surgery for benign colorectal disease serving as controls. Age distribution, routine blood analysis, duration of surgery, perioperative blood loss and anaesthesia was similar in the two groups. SF was quantitated using a commercial enzyme-linked immunosorbent assay. The preoperative plasma level of SF was normal in cancer patients as a whole. However, patients with disseminated colorectal cancer had higher levels of SF preoperatively compared to patients with localized colorectal cancer (p < 0.01) and controls (p < 0.005). On days 1, 2, and 7 days postoperatively, a rather pronounced increase in plasma SF was observed in cancer patients as well as in the controls. Three months after surgery, plasma SF had normalized in controls and in patients undergoing curative cancer treatment. Postoperative deep venous thrombosis (DVT) was detected in 23% of the cancer patients by means of phlebography. The preoperative values of SF in these patients were higher compared to patients not developing DVT (p < 0.05). Patients with colon cancer displayed higher SF in plasma than patients with rectal cancer (p < 0.05).

Adult↗