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Biomedical subjects

E Schlichting

Publications and source records attributed to E Schlichting.

At least 19 recordsLinked to original sources
PubMed2000

Hemodynamic changes and systemic activation of coagulation and fibrinolysis during controlled endotoxemia in pigs.

In this study, we have established a pig model that can combine extensive hemodynamic monitoring with simultaneous repetitive (serial) blood sampling for the study of multiple variables related to the hemostatic system. Sixteen healthy young pigs were studied to evaluate the influence of continuous endotoxin infusion on hemodynamic patterns and activation of coagulation and fibrinolysis. The chief aim of the study was to investigate the applicability of analytical methods primarily developed for use with human plasma samples in quantification of factors and reaction products of the porcine coagulation and fibrinolytic systems, and further, to use these methods to study the longitudinal changes in the plasma levels of these hemostatic variables as a consequence of endotoxin infusion. We found that acute, controlled endotoxemia induced a hemodynamic state of shock and reduced pulmonary gas exchange. Simultaneously, a gradual increase in peripheral blood mononuclear cell tissue factor activity was demonstrated, and increased maximally 5.5-fold 4 hours after onset of endotoxin infusion. Thrombin-antithrombin complexes increased in plasma to maximum levels after 3 hours, accompanied by an ethanol gelation test that was regularly positive after 1 to 2 hours, and fibrin monomer levels that gradually increased maximally 3.8-fold after 6 hours. These changes were followed by gradual decreases of both fibrinogen and factor VII levels, mainly due to consumption. Plasma levels of tissue type plasminogen activator activity peaked at 1.5 hours (11.3-fold increase), whereas the peak of plasminogen activator inhibitor-1 activity (14-fold increase at 4.5 hours) was delayed compared to tissue plasminogen activator and completely extinguished plasma tissue plasminogen activator activity. The sequential activation of coagulation and fibrinolysis established a procoagulant state favoring disseminated intravascular coagulation and microthrombus formation, potentially leading to multiple organ dysfunction.

Animals↗
PubMed1998

[Breast conserving surgery for breast cancer--local recurrence].

One of the disadvantages of breast conserving treatment compared with mastectomy is the higher rate of local recurrence. Even though a local recurrence has no influence on survival, it is a psychological trauma for the woman it affects. Breast conserving treatment has been practised at Ullevaal Hospital since 1986. This study is based on data from 216 consecutive cases of breast conserving surgery, from January 1986 to March 1996. Mean observation time was 29 months. Nine (4.2%) patients experienced a local recurrence. Age, histological grade, and the size of the tumor were identified as risk factors, whereas there was no correlation between histology, axillary node involvement, and surgical margins.

Adult↗
PubMed1998

[Introduction of a new surgical technique in rectal cancer].

Local recurrence rates following surgery for rectal cancer show considerable variation in different series, but impressive results (< 4% local recurrences after five years) have been presented by surgeons using total mesorectal excision as their operative technique. In Norway, local recurrence rates of 30% have been reported. Total mesorectal excision was introduced at Ullevaal Hospital in January, 1994 following a specific training programme. To enable us to compare the results, we followed-up two groups of patients who had undergone surgery for rectal carcinoma; one group (76 patients) before the introduction of total mesorectal excision and the other (76 patients) after total mesorectal excision was introduced. Anastomotic leakages were the main problem in the initial phase, but after faecal diversion became routine only one leakage was observed. After a median observation time of 28 months we had observed two patients (4.3%) with local recurrence in the total mesorectal excision group, and ten (23.8%) in the group where total mesorectal excision had not been performed.

Adult↗
PubMed1998

[Inflammatory bowel disease and pregnancy].

Inflammatory bowel disease (ulcerative colitis and Crohn's disease) is a chronic illness, often affecting people of reproductive age. Treatment involves drugs which have potential side effects and because of this pregnancy causes considerable concern. The course of the disease is not much affected by pregnancy. The relapse rate is only slightly increased when the disease is active at the time of conception. Relapses during pregnancy should be treated in the usual manner. Surgical intervention should be carried out on the same indications as in those who are not pregnant. Frequency of complications is not increased during pregnancy, at delivery or post partum. Sectio may be necessary in perianal disease. With few exceptions, drug treatment should be continued throughout pregnancy. No adverse effects are seen with normal doses of sulfasalazine, 5-amino-salicylic acid and steroids. Planned pregnancies should be started in periods of quiescent disease.

Animals↗
PubMed1998

[Prevention of infections among surgeons].

Accidental exposure to blood may represent a frightening experience for health care workers because of the risk of developing infectious diseases, such as hepatitis B and C virus and HIV infection. Recommendations for follow-up after occupational exposure to HIV- and hepatitis infected blood are presented. Post-exposure chemoprophylaxis decreases the risk of occupational HIV infection after percutaneous exposure and should be administered within two hours. Studies have shown that most accidents could have been avoided with better working routines during operations.

Blood-Borne Pathogens↗
PubMed1998

Immunocytochemical detection of isolated epithelial cells in bone marrow: non-specific staining and contribution by plasma cells directly reactive to alkaline phosphatase.

Detection of isolated tumour cells (TCs) in bone marrow (BM) from epithelial cancer patients by immunocytochemical (ICC) analysis seems to predict future relapse, but the reported percentages of positive BMs among patients with localized cancer show large variations and the number of detected TCs is low. This emphasizes the importance of thoroughly testing the methods in use. This study was performed to clarify to what extent positive staining of haematopoietic cells (HCs) interferes with the ICC detection of epithelial cells in BM. BM mononuclear cells (MNCs) from normal donors and stage I-II breast cancer patients were stained with anti-cytokeratin (CK) and isotype control monoclonal antibodies (MAbs) followed by alkaline phosphatase (AP)-based visualization of immunolabelled cells. In the ICC staining of normal donors by the anti-CK MAbs AE1/AE3 or A45-B/B3, rare immunoreactive cells were detected in 7/20 and 8/19 BMs, respectively. Morphological examination recognized all these cells as typical HCs. In the breast cancer patients (n = 257), anti-CK-positive cells were detected in 26.6 per cent, excluding cells with HC morphology. Using the same morphological criteria, isotype control-positive cells were detected in 5.4 per cent of patients. Some of the false-positive events were further analysed and cells with strong reactivity against the AP enzyme alone were detected. Double ICC staining recognized the majority of these AP directly-reactive cells as CD45-negative and human Ig kappa/lambda-positive, in accordance with the phenotype of mature plasma cells. Morphological evaluation and adequate controls are important to ensure the diagnostic specificity of micrometastases in BM. It is recommended that the number of BM MNCs included in negative controls should equal the number of cells in the diagnostic specimens.

Alkaline Phosphatase↗
PubMed1998

Effect of the introduction of total mesorectal excision for the treatment of rectal cancer.

BACKGROUND: Total mesorectal excision (TME) has been reported to reduce local recurrence and improve survival rates in patients with rectal carcinoma. This paper reports the problems that have arisen with the introduction of this new surgical technique. METHODS: This was a prospective study of two consecutive groups of patients: one who underwent TME (n = 76) and one who did not (non-TME, n = 76). RESULTS: Postoperative mortality rate in the non-TME and TME group was 5 and 7 per cent respectively, and the rate of anastomotic failure was 8 and 16 per cent respectively. Anastomotic leaks in TME patients were located in the mid and lower rectum. TME patients with anastomotic failure had lower anastomoses and a longer duration of operation than non-TME patients. Intraoperative problems were encountered in 71 per cent of the failures. All TME patients who had a leak required reoperation compared with 25 per cent of non-TME patients. TME patients without postoperative complications stayed significantly longer in hospital than non-TME patients. CONCLUSION: Anastomotic dehiscence increased after introduction of the TME technique but this improved with experience.

Adult↗
PubMed1996

[Lack of specialists in gastroenterological surgery].

Despite the fact that a prognosis in 1991 predicted a surplus of ten gastroenterological surgeons in 1994, several hospitals are now experiencing a lack of applicants. In order to define the scope of this problem, the Norwegian Gastroenterological Society and The Specialty Committee for Gastroenterological Surgery sent a questionnaire and made a telephone query to all Norwegian Surgical Departments in autumn 1995. There were 21 vacant posts and 27 specialists are still needed to carry out the tasks the hospitals are instructed to perform. An initiative must be taken to increase the capacity and geographical distribution of the education and improve the working conditions, and thereby job satisfaction, of gastroenterological surgeons.

Gastroenterology↗
PubMed1996

Interactions of endotoxin with human blood cells and serum proteins.

Endotoxin interacts with several plasma protein systems and blood cells, causing release of a multitude of endogenous mediators that contribute to the pathophysiological process of sepsis. Binding of 125I-labelled lipopolysaccharide, LPS, to human blood in vitro showed that the major part of the 125I-LPS was recovered in plasma, whereas only small amounts were retained in washed suspensions of granulocytes, erythrocytes, monocytes and lymphocytes, respectively. Whole leukocyte preparations or isolated subpopulations incubated with 125I-LPS or fluorescein-conjugated LPS followed by autoradiography, flow cytometry or immunofluorescence microscopy showed unequivocally that monocytes bound much more LPS than did granulocytes and lymphocytes. Lipoprotein electrophoresis followed by autoradiography showed that 125I-LPS bound to all the purified lipoprotein fractions, which was also confirmed by gel filtration chromatography. These findings demonstrate that monocytes represent the most important blood cell for LPS binding and that radiolabelled LPS is able to bind to lipoproteins as well as to other serum constituents.

Blood Proteins↗
PubMed1995

Monitoring of tissue oxygenation in shock: an experimental study in pigs.

OBJECTIVE: To evaluate different methods and markers for assessing adequacy of tissue oxygenation in shock. DESIGN: Prospective, controlled animal trial. Two groups of six pigs, subjected to either a superior mesenteric artery occlusion shock or a hemorrhagic shock. A third group of five pigs served as controls. SETTING: Hospital animal research laboratory. SUBJECTS: Anesthetized, ventilated, juvenile, domestic pigs. INTERVENTIONS: Clamping of the superior mesenteric artery for 5 hrs, followed by reperfusion or withdrawal of blood to achieve a mean arterial pressure of 50 mm Hg for 3 hrs was performed, followed by resuscitation using the withdrawn whole blood. Invasive hemodynamic monitoring with arterial and pulmonary artery catheters was done. A tonometer was placed in the terminal ileum. MEASUREMENTS AND MAIN RESULTS: Ileal intramucosal pH, systemic base excess (or deficit), lactate concentration in systemic venous and arterial blood as well as in portal blood, ascitic fluid, and thoracic duct lymph, hemodynamics, and oxygen-related variables were measured. Five hours of intestinal ischemia caused no significant changes compared with the control group with regard to base excess or any of the hemodynamic or oxygen-related variables measured. However, lactate concentrations in the ascitic fluid and intramucosal pH were significantly altered within 1 hr of regional ischemia. Lactate concentration in the thoracic duct lymph was significantly increased after 2 hrs of ischemia, while lactate concentrations in the portal, systemic, and arterial blood were significantly increased after 2 hrs of regional ischemia. Reperfusion was associated with a high mortality rate, and only one animal survived the reperfusion period. In the hemorrhagic shock group, cardiac output and mean arterial pressure were significantly (intentionally) decreased 60 mins after the hemorrhage, while the heart rate, base excess, and systemic and portal blood lactate concentrations were significantly increased after 2 hrs of general hypoperfusion compared with those values in the control group. Ileal intramucosal pH, mixed venous oxygen saturation, oxygen delivery, oxygen extraction, and lactate concentrations in the arterial blood and thoracic duct lymph were significantly different from those values in the control group 3 hrs after the onset of hemorrhagic shock. Reperfusion induced a normalization of the hemodynamic and metabolic status of the animals. CONCLUSION: Many conventional markers of tissue hypoxia are useful when assessing general hypoperfusion, whereas intestinal intramucosal pH is the only reliable and clinically useful indicator of inadequate regional intestinal tissue oxygenation.

Animals↗
PubMed1995

Freshly isolated tumour-infiltrating T-lymphocytes have a high cytotoxic potential, as measured by their ability to induce apoptosis in the target cell.

To test if freshly isolated tumour-infiltrating lymphocytes (TIL) can induce apoptosis in a target cell, we have combined two previously described methods. Because TIL predominantly are T-lymphocytes, we have applied a redirected approach. When the target cells that express anti-human-CD3 monoclonal antibodies in their membranes bind to the T cell receptor-associated CD3-complex, signals are generated, which activate T cell effector mechanisms. This approach circumvents problems with MHC-restriction and allows for functional testing of all T cells, irrespective of their clonal specificity. In order to assay for induction of DNA fragmentation, we have labelled the target cell nuclei with [3H]thymidine. Upon harvesting fragmented DNA are washed away. Electrophoretic analysis of the fragmented DNA demonstrated the characteristic 'ladder' pattern, consistent with apoptosis. This rapid and simple assay monitors the capacity of different T cells to induce apoptosis in the target cell. It depends on intercellular interactions and clearly discriminates between different T cell subsets. With this assay we demonstrate the functional integrity of the cytotoxic effector arm of freshly isolated TIL.

Adenocarcinoma↗
PubMed1995

Endothelin and hemodynamic responses to superior mesenteric artery occlusion shock and hemorrhagic shock in pigs.

Endothelin is a novel, potent, endogenous vasoconstrictor derived predominantly from endothelium and macrophages. Release of endothelin-1 (ET-1) into biological fluids was determined by radioimmunoassay in pigs undergoing either a hemorrhagic (3 h) or superior mesenteric artery (SMA) occlusion (5 h) shock followed by reperfusion (90 min) or a control group which was observed for 8 h. After surgery, there was a significant increase in ET-1 in jugular and carotid plasma, lymph, and ascitic fluid in all three models. The portal plasma ET-1 level was significantly increased (p < .05, assessed by the Spearman rank coefficient rho) in both shock models, but no significant increase was noted in the control group. In the SMA occlusion shock model, four pigs died within 30 min of reperfusion, and these animals had a much higher level of portal ET-1 (22.3 +/- 5.5 fmol/mL) than the two pigs that were alive by the end of the observation period (11.5 +/- 1.3 fmol/mL). Reperfusion in the SMA occlusion shock model induced a critical form of circulatory shock characterized by hypotension, decreased cardiac output, and decreased left and right ventricular stroke work index, and death occurred usually within 90 min. Reperfusion of the shed blood in the hemorrhagic shock model almost normalized the hemodynamic derangements caused by the hypovolemia (with the exception of RVSWI), and the portal plasma and ascitic ET-1 levels decreased. These results indicate that ET-1 is released from the gut in response to both general hypoperfusion and selective intestinal ischemia and reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Alterations in mucosal morphology and permeability, but no bacterial or endotoxin translocation takes place after intestinal ischemia and early reperfusion in pigs.

Ischemia and reperfusion of the gut may be an important etiological factor in the development of multiple organ failure. We have used a hemorrhagic and a superior mesenteric artery (SMA) occlusion shock model in pigs to estimate the effect of ischemia and reperfusion on intestinal morphology, mucosal permeability, and the occurrence of bacterial or endotoxin translocation. Mucosal ulceration and necrosis were found in the SMA shock model, while the morphological changes were less pronounced in the hemorrhagic shock model. Scanning electron microscopy showed shrinkage of the villi and plugging of the colonic crypts in both shock models. Enterocyte cell kinetics was investigated using 5-bromo-2'-deoksyuridine (BrdU) incorporation and immunovisualization by anti-BrdU antibodies. Cell renewal was almost completely lost from the jejunum to the rectum in both shock models. Intramucosal pH was measured using a tonometer placed in the terminal ileum. Segments of intestinal mucosa were mounted in Ussing chambers, and permeability was measured using radiolabeled probe molecules of differing molecular weights. Augmented molecular flux of inulin (M(r) 5.000) and mannitol (M(r) 182) and loss of short circuit current (Isc) and transepithelial potential difference (PD) were found in mucosae from both shock models. Endotoxin was demonstrated in the ascitic fluid in both shock models; 9.5 (2.7-14.3) (median and 95% confidence interval) EU/mL in the SMA occlusion model and 16.0 (4.9-29.4) EU/mL in the hemorrhagic shock model), but the levels were not significantly higher than in the control model 6.5 (4.3-34.0) EU/mL.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

[Surgical treatment of gastrointestinal malignant melanoma].

Malignant melanoma is the most common metastatic lesion of the intestine, found at autopsy in approximately 60% of patients who die from melanoma. Common symptoms include bleeding, perforation and ileus/subileus. Patients with such symptoms should be operated on immediately, if they are not too reduced because of advanced disease. Long-term survival (five years) has been achieved in 34 of 179 (19%) of stage IVA melanoma patients after a radical operation procedure. Surgical removal of gastrointestinal metastases provides effective palliation in 80-95% of patients, who undergo laparotomy. We describe two patients with gastrointestinal metastases from malignant melanoma. A 33 year-old man had a large melanoma metastasis removed (non-radically) from the small intestine. He recovered rapidly, and experienced good palliative effect for three months, but died from a recurrence of the disease six months after operation. The other patient had a melanoma metastasis in the right lobe of the liver, which was treated by right hemihepatectomy. There has been no recurrence ten months after operation. We recommend surgical removal of abdominal melanoma metastasis if the surgery can be performed without unacceptable risk.

Adult↗
PubMed1994

Limited heterogeneity in the T-cell receptor V-gene usage in lymphocytes infiltrating human colorectal tumours.

The presence of T lymphocytes in solid tumours may reflect an ongoing immune response against the transformed cells. We have used polymerase chain reaction (PCR) technology to investigate the T-cell receptor variable-region gene (V-gene) usage in freshly isolated tumour-infiltrating lymphocytes (TILs) to look for a possible oligoclonality of T cells in the tumour area. We used 19 different V beta-family-specific primers. Peripheral blood lymphocytes and lamina propria lymphocytes from the same patients were also tested by PCR. Our results demonstrate a limited heterogeneity in the V-gene usage of TILs from seven patients with colorectal cancers, suggesting a local antigen-driven immune response at the tumour site.

Adenocarcinoma↗
PubMed1994

Human colorectal tumour infiltrating lymphocytes express activation markers and the CD45RO molecule, showing a primed population of lymphocytes in the tumour area.

This study investigated the phenotype of freshly isolated human tumour infiltrating lymphocytes (TIL) from 14 patients with colorectal tumours, and compared them with lymphocytes derived from the lamina propria of the unaffected mucosa and with lymphocytes derived from peripheral blood of the same patients. It was found that TIL expressed the activation markers CD25 and HLA-DR to a higher extent than the peripheral blood lymphocytes (p = 0.01), and that both lamina propria lymphocytes and TIL preferentially expressed the CD45RO + phenotype, associated with memory cells, in contrast with peripheral blood lymphocytes [corrected]. Both lamina propria lymphocytes and TIL contained few natural killer (NK) cells (CD3-CD56+) compared with peripheral blood lymphocytes (p = 0.001), and this was reflected in the cytotoxicity assays. After 1 to 2 weeks in culture with interleukin-2 100 U/ml, lymphocytes from all three compartments had a high cytolytic activity against all targets tested, consistent with the lymphokine activated killer cell phenomenon. No increase in the number of NK cells was noted after culture, but 20-30% of the T cells now coexpressed the CD56 molecule. This was most prominent in the CD8+ subset, but lymphokine activated killer cell activity was found in both CD4+ and CD8+ subsets. Possible tumour escape mechanisms are discussed.

Colonic Neoplasms↗
PubMed1994

Lipoproteins do not modulate the tissue factor activity, plasminogen activator or tumour necrosis factor production induced by lipopolysaccharide stimulation of human monocytes.

Upon stimulation with lipopolysaccharides (LPS), monocytes are able to produce tissue factor (TF), the most powerful physiological procoagulant substance known. In several assay systems LPS bound to lipoprotein has been reported to be less active than unbound LPS in stimulating monocytes. In the present study the LPS-induced TF activity was, however, not prevented by lipoproteins (VLDL, LDL, HDL). In fact, the very low density (VLDL) fraction further increased the TF inducing capacity of LPS. The lipoproteins per se mediated reduced plasminogen activator (PA) production in monocytes. LPS had an even more and significant depressing effect on PA production, which was not further decreased in the presence of lipoproteins. Furthermore, LPS-induced release of tumour necrosis factor (TNF), a marker of monocyte activity, was not inhibited by lipoproteins. Our experiments suggest that lipoproteins do not render LPS less effective in stimulating TNF release, procoagulant and fibrinolytic activities in human monocytes.

Cells, Cultured↗