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Biomedical subjects

E Schlichting

Publications and source records attributed to E Schlichting.

36 records · Page 2Linked to original sources

[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↗

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↗

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↗

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↗

Endotoxin liberation from Neisseria meningitidis correlates to their ability to induce procoagulant and fibrinolytic factors in human monocytes.

Endotoxin released from different strains of Neisseria meningitidis were studied for their ability to induce procoagulant (tissue factor, TF), fibrinolytic (plasminogen activator, PA) and antifibrinolytic (plasminogen activator inhibitor 2, PAI-2) factors in human monocytes. Two meningococcal strains that liberate endotoxin (E+; 270+ and 840+) and 2 non-liberating (E-; 270- and 840-) strains were used. The endotoxin activity in culture filtrates of these strains was monitored with the Limulus amoebocyte lysate (LAL) test. There was a marked difference between E+ and E- strains in their ability to liberate endotoxin. Suspensions of whole bacteria of all 4 strains induced a significant (14-19-fold) increase in monocyte TF expression when present in concentrations > 10(5) CFU/ml. At lower concentrations (10(4) CFU/ml), E+ strains were clearly more potent stimulators of TF synthesis than E- strains. Culture filtrates of E+ strains were up to 10(4)-fold more potent in inducing TF synthesis than filtrates from E- strains. This marked difference in inducing potency between E+ and E- strains was also observed when monocyte PAI-2 synthesis was examined. The PA expression, on the other hand, was suppressed when monocytes were incubated in the presence of culture filtrates, especially filtrates from the E+ strains. The increased procoagulant and antifibrinolytic activity, together with reduced profibrinolytic activity of monocytes, was closely correlated to the amount of endotoxin measured in the culture filtrates. These changes may contribute substantially to the coagulopathic state seen during systemic meningococcal disease.

Cells, Cultured↗

Ploidy and survival in resectable pancreatic cancers. A retrospective study over 9 years.

OBJECTIVE: To evaluate the association between ploidy and operability and prognosis in pancreatic cancer. DESIGN: Retrospective study. SETTING: Ullevaal Hospital and the National Hospital of Norway, Oslo. SUBJECTS: 148 patients with histologically verified pancreatic cancer diagnosed between 1980 and 1988. INTERVENTIONS: 29 patients had radical resections (18 Whipple procedures and 11 total pancreatectomies). Archival tissue was investigated in the blocks from these tumours, and from five patients who had only a biopsy taken, by DNA flow cytometry. RESULTS: 26/29 tumours excised radically had diploid DNA stemlines. Two of the three aneuploid stemlines were hyperdiploid, and the third was almost triploid. Among the five inoperable tumours, two were aneuploid and three diploid. The patients who underwent radical operations lived a median of 11.5 months (range 0-82), compared with a median of 4 months (range 0-58) for those whose tumours were inoperable. Six of the 29 patients were still alive without signs of recurrent disease 51.5 months (range 41-82) after operation. All but one of these tumours had diploid DNA stemlines, and synthesis (S) phase fractions below the median value for the whole group. CONCLUSION: DNA ploidy and S phase fraction are prognostic factors in pancreatic cancer.

Aged↗

[Pseudomembranous colitis. Surgical treatment].

Pseudomembranous colitis is an inflammatory intestinal disease that is usually secondary to antibiotic treatment. The disease upsets the normal bacterial flora of the large intestine. Therapy consists of fluid replacement, discontinuation of broad-spectrum antibiotics and treatment with vancomycin or metronidazole. In severe or resistant cases surgical treatment is required. We describe one case history and give some guidelines for surgical treatment.

Cecum↗

[Indirect measurement of intramucosal pH in the gastrointestinal tract using a tonometer. A useful marker of tissue oxygenation in critically ill patients].

Multiple organ failure may develop as a consequence of defective tissue oxygenation, particularly in the gut. Measurements of intramucosal pH (pHi), accomplished by means of a tonometer placed in the stomach or in the sigmoid colon, seem to monitor the degree of mucosal oxygenation very good. The tonometer technique is noninvasive and easy to perform. pHi may be useful as an index to guide therapeutic interventions in critically ill patients.

Critical Care↗

Serum carcinoembryonic antigen in relation to survival, DNA ploidy pattern, and recurrent disease in 406 colorectal carcinoma patients.

Serum carcinoembryonic antigen (CEA) levels in relation to survival, flow cytometric DNA ploidy pattern, Dukes stage, and recurrent disease was prospectively evaluated in 406 patients with colorectal carcinoma. In 246 patients (61%) the carcinomas were DNA aneuploid. Increased preoperative CEA levels (> 5 micrograms/l) were found in 151 of 363 evaluable patients (42%). Dukes stage-B patients with preoperative CEA elevation showed significantly poorer prognosis than those with normal CEA values (p = 0.001). A weak but significant correlation was found between preoperative CEA level and Dukes stage (Kendall's tau = 0.25, p < 0.01). Of 50 evaluable patients with clinical recurrence and postoperative normal or normalized CEA levels, 28 (56%) had a rise in CEA before or at the time of clinical recurrence. The sensitivity of the CEA test for primary and for recurrent disease was not significantly different in the DNA aneuploid and the DNA near-diploid groups.

Adenocarcinoma↗

Association between DNA ploidy pattern and cellular atypia in colorectal carcinomas. A new clinical application of DNA flow cytometric study?

Fresh tissue specimens from 406 colorectal carcinomas were analyzed by DNA flow cytometric study, and the DNA ploidy pattern was compared with Dukes' stage, histologic grade, and degree of cellular atypia. Sixty-one percent of the carcinomas had a distinct aneuploid DNA pattern. The proportion of aneuploid carcinomas was significantly higher in the advanced Dukes' stages than in the localized ones. A highly significant association was found between DNA ploidy pattern and degree of cellular atypia, whereas no association was demonstrated between DNA ploidy pattern and histologic grade. This finding might indicate that cellular atypia has a stronger prognostic impact than the growth pattern of the tumor. The authors suggest that flow cytometric DNA quantification may replace assessment of cellular atypia in the histologic evaluation. Furthermore, together with earlier findings by others, these results indicate that the degree of cellular atypia may be conserved during the development from adenomas to carcinomas.

Adenocarcinoma↗

[Pancreatic cancer. Treatment and results].

Between 1980 and 1989, 151 patients were treated for adenocarcinoma of the pancreas. One fifth of the patients underwent radical surgery whereas 1/3 had a palliative operation. Leakage from the pancreatico-duodenal anastomosis, constructed with a mucosa to mucosa technique, did not occur in patients operated with pancreatico-duodenal resection (n = 19). The postoperative lethality in this group was 5%. Median overall survival time was four months, after a radical operation 11.5 months and after a palliative operation five months. Five patients with cancer of the papillary region had a median survival time of 40 months and four patients are still alive.

Adenocarcinoma↗

[Use of resources in the treatment of pancreatic cancer].

We calculated the costs of surgery for pancreatic cancer in 151 patients treated for carcinoma of the pancreas at Ullevål sykehus, University of Oslo, during the period 1980-89. The costs of the diagnostic process and the hospital stay were calculated separately. We found that radical surgery cost about NOK 80,000 more than a palliative operation. The median survival time after radical operation was only 11 months, compared with five months after palliative surgery. We are discussing the price of the surgery in relation to the results. We stress the importance of restrictive selection criteria for radical surgery of pancreatic cancer and conclude that the higher cost of radical surgery as compared with palliative procedures is acceptable.

Adult↗

[Study and diagnosis of pancreatic cancer].

The most common initial symptom was abdominal pain. Other frequent debut symptoms were loss of weight and jaundice. ERCP and PTC were found to be the best diagnostic procedures. CT or ultrasonography were normal in 10-20% of the patients. Nearly all tumors of the pancreas were found by the ERCP procedure. We also used angiography to evaluate operability of the pancreas tumor. Angiography was found to be a very uncertain diagnostic procedure, however, and we have now decided not to use angiography in the future evaluation of patients with cancer of the pancreas.

Adult↗

[Splenectomy in hematologic diseases].

We present the results of splenectomy in 45 patients with haematological diseases during the period 1975-85. Of 16 patients with immunologic thrombocytopenia, splenectomy resulted in a satisfactory and sustained platelet elevation in 11 (69%). Splenectomy corrected anaemia in all five patients with hereditary spherocytosis. Of seven patients with autoimmunohaemolytic anaemia, four responded satisfactorily. Postoperative complications occurred in ten of 45 patients (22%). There was no post-operative mortality. Only 49 per cent of the patients had received antipneumococcal vaccination. This is not satisfactory, and all unvaccinated, splenectomized patients should be offered vaccine. If possible, the vaccination should be performed before operation.

Adolescent↗

Kinin antagonist does not protect against the hypotensive response to endotoxin, anaphylaxis or acute pancreatitis.

The vasodilator bradykinin (Bk) has long been though to participate in shock induced by endotoxemia, anaphylaxis and acute pancreatitis. Recently developed kinin antagonists have made it possible to test this hypothesis. We studied the effect of two of them. DArg0Hyp3-Thi5.8-DPhe7-Bk (45 and 220 micrograms/kg/min) and Lys-Lys-Hyp2-Thi5.8-DPhe7-Bk (100 micrograms/kg/min) on the early hypotensive response to Escherichia coli lipopolysaccharide (LPS). Rats infused with the antagonist vehicle were used as controls. At 45 micrograms/kg/min, DArg0-Hyp3-Thi5.8-dPhe7-Bk prevented the hypotensive response to high doses of Bk; however, neither antagonist prevented the hypotensive response to LPS. Circulating kinins measured 3 min after injecting LPS or vehicle were similar (16.3 +/- 1.4 vs. 26.0 +/- 7.2 pg/ml; P greater than .23). In allergically sensitized rats, 500 micrograms/kg/min DArg0-Hyp3-Thi5.8-DPhe-7-Bk did not alter the hypotensive (anaphylactic) response to antigen challenge (P greater than .38). Similarly, hypotension caused by development of acute pancreatitis in rats was not prevented by infusion of DArg0-Hyp3-Thi5.8-DPhe7-Bk at 200 micrograms/kg/min, 10 min) (P greater than .69). These results indicate that in the rate formation of kinins is not a major contributor to the hypotensive response observed in early endotoxemia, anaphylaxis and acute pancreatitis.

Acute Disease↗