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Biomedical subjects

E H Farthmann

Publications and source records attributed to E H Farthmann.

At least 55 records · Page 3Linked to original sources

Raf-1 kinase, epidermal growth factor receptors, and mutant Ras proteins in colonic carcinomas.

Epidermal growth factor receptors (EGFR) and ras mutations are known to play a significant role in controlling cell growth and tumor promotion. Both of them transmit mitogenic signals to the nucleus by activation of Raf-1 kinase. In this study, the expression of EGFR and mutant Ras proteins, and, for the first time, the expression, phosphorylation and kinase activity of Raf-1 kinase have been determined in paired samples of colorectal cancer and mucosa. The tumor and mucosa samples did not differ significantly with regard to Raf-1 kinase content and activity. A major difference between tumors and mucosa was found, however, in the phosphorylation of Raf-1. Most of the mucosa samples (13/20), but only 1/20 of the cancer samples, contained hyperphosphorylated Raf-1. EGFR were significantly (p = 0.0025) decreased in the tumors. The decreased phosphorylation of Raf-1 in colonic carcinomas could be the result of activation of Raf-1 phosphatases or inactivation of kinases phosphorylating Raf-1. New forms of treatment based on EGFR overexpression do not seem to be suitable for the majority of colonic cancers.

Adenocarcinoma↗

Different protective effects of tauroursodeoxycholate, ursodeoxycholate, and 23-methyl-ursodeoxycholate against taurolithocholate-induced cholestasis.

The coinfusion of tauroursodeoxycholate (TUDC) prevents taurolithocholate (TLC) -induced cholestasis. 23-Methyl-ursodeoxycholate (MUDC) is a side-chain derivative of ursodeoxycholate (UDC). If conjugation with taurine is important for the protective effect of UDC, the MUDC may not be as able as TUDC to prevent TLC-induced cholestasis since it is poorly amidated by the liver. To answer this question, isolated livers of adult Sprague-Dawley rats were coinfused with MUDC (UDC, TUDC) and TLC. After 15 min, inflow rates of the bile acids were doubled. In further experiments taurine in excess was added to the coinfused bile acids. The uptake of bile acids was >90% in all groups, irrespective of whether they were perfused alone or in combination. Single perfusion of TLC caused a rapid decrease in bile flow. UDC and MUDC were hypercholeretic; TUDC moderately choleretic. During coinfusion experiments, TUDC not only completely abolished cholestasis but in addition increased bile flow and biliary bile acid secretion. UDC did prevent TLC cholestasis at the lower inflow rates. At high inflow rates, bile flow decreased significantly. Addition of taurine to this bile acid combination did not significantly improve the anticholestatic effect of UDC. At low and high infusion rates of MUDC, cholestasis induced by TLC was reduced very little. Cumulative bile flow over 30 min fell by approximately 70% as compared to that of singly perfused MUDC. Addition of taurine to the coinfused MUDC/TLC slightly, but less significantly, improved the anticholestatic effect of MUDC. Since MUDC is by far less protective than UDC (and TUDC) despite similar physiochemical properties, it is concluded that taurine conjugation of UDC seems to be a prerequisite to prevent TLC-induced cholestasis. The results imply that treatment of cholestatic liver diseases with taurine-conjugated UDC might be more appropriate than with unconjugated UDC in cases where taurine conjugation is defective or where taurine depletion has occurred.

Animals↗

Emergency laparoscopy. Technical support for the laparoscopic diagnosis of intestinal ischemia.

BACKGROUND: Laparoscopic diagnosis of intestinal ischemia is difficult. Dark-colored bowels are not a reliable indicator for infarction, because there is no correlation between color and oxygenation. The same picture is produced by intraluminal blood or feces. False diagnoses are described. METHODS: We analyzed various techniques for assessing intestinal oxygenation and perfusion to support laparoscopic diagnosis. In this study laparoscopy was performed on eight pigs. A 10-cm segment of intestine was fixed to the abdominal wall and rendered ischemic. Measurements of the ischemic segment and normal intestine were taken using laser-Doppler, Doppler ultrasound, spectrophotometer, and pulse oximeter. Doppler ultrasound and pulse oximetry were unsuitable in our model, as was laser-Doppler flowmetry. RESULTS: Only the spectrophotometer proved a highly sensitive means of assessing bowel oxygenation. CONCLUSIONS: This method provides the desired additional information about intestinal oxygenation, thus helping to interpret the laparoscopic picture of dark bowels.

Animals↗

Comparison of laparoscopic handsewn suture techniques for experimental small-bowel anastomoses.

Laparoscopic techniques have only rarely been applied to procedures on the small bowel. A comparison of three handsewn intracorporeal anastomoses was carried out. Thirty pigs were divided into three groups, and a different technique was used in each group (SK, single knot; RS, running suture; CL, clip suture). Half of the animals had a relaparoscopy on day 4. The duration of the procedure was recorded, and the quality of anastomotic healing was assessed by morphological, radiological, mechanical, and biochemical examinations. The animals were sacrificed on postoperative day 14. The anastomoses in the SK group took significantly longer than in the RS or CL groups. The mean duration of relaparoscopy was 28 min. Bursting pressure values and hydroxyproline concentrations were without any significant difference. The SK and CL groups showed a good alignment of the layers and the RS showed necrosis and overlying mucosa. Most complications were noted in RS. The results demonstrate that manual small-bowel anastomoses can be performed laparoscopically. Single-knot and clip sutures are reliable techniques. The ongoing development of new instruments and the three-dimensional technique will basically improve the construction of intracorporeal anastomoses.

Anastomosis, Surgical↗

[Diagnosis and therapy of diaphragmatic rupture after blunt thoracic and abdominal trauma].

Diagnosis of diaphragmatic rupture is often missed after blunt thoracic and abdominal injuries because diaphragmatic injury does not play an important role beside severe injuries of intrabdominal and/or thoracic organs. Between 1976 and 1993, 141 patients were treated for traumatic injury of the diaphragm. In 42 patients with penetrating injuries following stab or shot wounds diaphragmatic lesions were diagnosed by the emergent surgical therapy. 99 had diaphragmatic tears from blunt thoracic or abdominal trauma by accidents. 14 of 99 patients sustained isolated diaphragmatic rupture, in 85 the rupture was combined with other injuries, 24 had fractures of the pelvic ring. Preoperatively the following diagnostic procedures were performed: chest radiograph in 99 patients, abdomen radiograph in 75, contrast radiographs in 34, angiography in 9, sonography in 74 and computed tomography in 48. Sensitivity and specificity of these diagnostic methods depend on the dimension of intrathoracic prolaps of abdominal organs. The sensitivity of contrast radiographs ranged from 72-78%. With the additional experience of ultrasonography since 1985 the sensitivity came up to 82%. In 11 patients additional diaphragmatic rupture was diagnosed by laparotomy indicated by liver and/or splenic rupture. Therapy of diaphragmatic injury was performed in 83 patients within 4 days, in 9 within 4 months and in 7 later than one year. For diaphragmatic repair 87 patients underwent laparotomy and 12 thoracotomy. Local complications were found in 13 patients (13.1%). 19 patients (19.2%) died postoperatively due to accompanying injuries.

Abdominal Injuries↗

[Strategy and results of advanced tumors in emergency situations].

In this retrospective trial we examined 142 patients with advanced unresectable cancer, who had bowel obstruction, bleeding, bowel lesion and abscesses and who were treated with different surgical procedures (resection, bypass, enterostomy). Mean survival rate was 8.6 months (range: 0-57 months). The mortality rate reached 21.7%. Surgical reintervention was necessary in 15.8% because of bowel obstruction and did not influence the survival rate. Despite advanced tumor disease and intestinal obstruction most patients had a good quality of life after surgical intervention.

Abdominal Abscess↗

Expression of GM-CSF and a functional GM-CSF receptor in the human colon carcinoma cell line SW403.

Only little is known about the expression of a functional granulocyte-macrophage colony-stimulating factor receptor (GMR) and its ligands in human colon carcinoma cell lines. To obtain more information on this subject, we investigated the human colon carcinoma cell line SW403, and we were able to demonstrate the constitutive synthesis of a 85-kDa GMR in SW403 cells. After stimulation with 10% fetal calf serum, GM-CSF transcripts were expressed as well. The incubation of SW403 cells with GM-CSF resulted in an intensive down-regulation of the activity of the interferon-gamma-receptor gene, which could be reconstituted by simultaneous addition of an anti-GM-CSF antibody. GM-CSF induced an activation of tyrosine-phosphorylated protein kinases with molecular weights in the range of 30 to 210 kDa, but it had no effect on the DNA synthesis of SW403 cells.

Adenocarcinoma↗

Expression of gastrin, gastrin/CCK-B and gastrin/CCK-C receptors in human colorectal carcinomas.

To investigate further the presence of an autocrine proliferative loop involving gastrin in colorectal carcinomas and to clarify the receptor responsible, 102 human colorectal carcinomas and 10 hepatic metastases were investigated for the expression of the genes encoding gastrin, the gastrin/CCK-B receptor and the gastrin/CCK-C receptor. Levels of RNA expression were assayed by RNase protection assay. In addition, gastrin/CCK receptors on crude membranes of tumour tissue were assayed by radioligand binding. High-affinity gastrin/CCK-B receptors were not detected in any of the carcinomas investigated, whereas in 36% low-affinity binding was observed, consistent with the expression of the gastrin/CCK-C receptor. RNase protection assay detected the RNA for the gastrin/CCK-B receptor in 11% of the carcinomas investigated, whereas the RNA for the gastrin/CCK-C receptor was demonstrated in 75% and the RNA for gastrin in 86% of the carcinomas investigated. These results confirm the recent demonstration of progastrin fragments in colorectal carcinomas. One possible explanation for progastrin expression is that such progastrin fragments may participate in an autocrine proliferative loop. The receptor involved in this loop is more likely to be the low-affinity gastrin/CCK-C receptor rather than the gastrin/CCK-B receptor, which is rarely expressed in colorectal carcinomas.

Binding, Competitive↗

Change of zonal bile acid processing after partial hepatectomy in the rat.

The aim of this study was to analyze whether partial hepatectomy alters functional liver heterogeneity with respect to bile acid processing. One, 5 and 21 days after liver resection (approximately 80% of liver mass) in male Sprague-Dawley rats (300-400 g), isolated livers were perfused in either the antegrade or the retrograde direction, respectively, with 32 nmol cholate/min per g liver. Uptake, metabolism and biliary secretion kinetics were determined by bolus injection of 14C-cholate. Uptake and biliary recovery (within 30 min) of cholate were > 90% in all groups. One day postresection, liver mass had already doubled and it regenerated to over 80% 5 days after resection. Serum bile acid concentration increased rapidly, peaking 6 h after resection (176.7 +/- 28.5 mumol/l) (mean +/- SEM). Twenty-one days after resection it fell to control values (23.2 +/- 3.8 mumol/l). T25 (T50), the time (min) necessary to excrete 25% (50) of the bile acid load into bile, was strikingly different between periportal and pericentral cells of controls (1.8 vs 5.7 and 3.4 vs 8.1). Five days after resection this difference became smaller (1.4 vs 2.9 and 2.8 vs 5.5) due to accelerated biliary cholate secretion in pericentral cells. Pericentral cells of controls metabolized cholate more extensively to taurocholate (approximately 83%) and glycocholate (approximately 13%) than periportal cells of controls (65%, 10%), leading to a 5-fold higher proportion of unmetabolized cholate in periportal than pericentral cells (25% vs 5%). Five days after resection the percentage of taurocholate decreased significantly at the expense of an increased formation of glycocholate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Pattern of bile acid regurgitation and metabolism during perfusion of the bile duct obstructed rat liver.

Bile acid processing in the long-term, bile duct obstructed rat liver was studied ex vivo. Twenty four and 72 h, respectively, after bile duct obstruction the isolated liver was perfused with taurodeoxycholate (16 nmol/min per g liver) the bile duct still being closed. Uptake, metabolism and regurgitation profile were traced by bolus injection of tritium-labeled bile acid; in addition, concurrent histological changes were examined by light- and electron microscopy. Ligation caused dilatation of the intrahepatic ductular branches and increased the serum bile acid concentration to 740 +/- 75 microM (controls: 16 +/- 2.12), reaching its maximum within 24 h. At 16 nmol/min per g liver uptake rate was > 96% in controls and in bile duct obstructed rats. Maximal uptake rates (assessed separately) differed between controls and bile duct obstructed rats (700 nmol/min per g liver vs. 460). Controls excreted more than 80% of labeled bile acid in bile within 10 min after bolus injection. Biliary recovery of label was virtually completed after 30 min. In bile duct obstructed rats excretion of label back to the perfusate effluent (regurgitation) started quantitatively 5 min after bolus application and peaked between 10 and 40 min; after 80 min, effluent recovery was incomplete (about 60% of bolus injected). Biliary bile acids of controls consisted of about 20% taurodeoxycholate-metabolites; bile acids in the perfusate effluent of bile duct obstructed rats of about 55%. The major metabolite in all animal groups was taurocholate; minor metabolites were tauroursocholate, tauro-3 alpha,7 = 0,12 alpha-cholanoic acid and 3-sulfo-taurodeoxycholate. Histologically, inflammation and periportal edema were present after 1 day of bile duct obstruction. After 3 days, marked proliferation of bile ductules was the dominant histological feature. It is concluded that during initial bile duct obstruction, bile acid processing is not altered, although ultrastructural alterations occur early.

Animals↗

Morphological and functional characteristics of tumor-infiltrating lymphocytes from human colorectal cancers after stimulation with rIL-2.

Tumor-infiltrating lymphocytes (TILs) from colorectal cancers were separated from tumor cells by enzymatic and mechanical tissue disaggregation and discontinuous density gradients. Peripheral blood lymphocytes (PBLs) were isolated using the same procedure. The freshly separated TILs and PBLs were analyzed phenotypically by flow cytometry. The CD4+/CD8+ ratios of the freshly isolated TILs and PBLs were comparable (> 1 in both lymphocyte populations). CD25+, HLA-DR+ and CD56+ cells were significantly more frequent in the TIL than in the PBL population. However, the number of CD45RA+ cells was lower in the TILs as compared to PBLs, while CD29+ accumulated by about 90% in TILs. TILs and autologous PBLs were expanded in vitro with rIL-2. The mean rate of proliferation after 4 weeks was 642-fold in TIL cultures and 335-fold in PBLs. More than 90% of the rIL-2-expanded lymphocytes expressed CD2 and the great majority was CD29+. Stimulation with rIL-2 in vitro induced an outgrowth of CD56+ cells mainly in the TILs. Accordingly the expression of CD3+ and alpha/beta receptor in the TILs was low. Those cells which phenotypically represented lymphokine-activated killer cells displayed a lytic activity against the autologous tumor as well as against allogeneic K562 and Daudi targets. In accordance with the better proliferative response of TILs in long-term cultures with rIL-2, the lytic activity of TILs against autologous and allogeneic tumor targets was significantly higher as compared to PBLs.

Adult↗

Intraperitoneal micro-organisms and the severity of peritonitis.

OBJECTIVE: To find out if there was any correlation between the type or number of pathogenic bacteria in peritoneal exudate, the values of various prognostic scores, the inflammatory response, and the outcome, in patients with peritonitis. DESIGN: Prospective open study. SETTING: University hospital, Germany. SUBJECTS: 51 Consecutive patients with secondary peritonitis. INTERVENTIONS: Laparotomy within 12 hours of admission or within 8 hours of diagnosis in 9 patients with postoperative peritonitis. MAIN OUTCOME MEASURES: Correlation between the severity of the disease (APACHE II score, Septic Severity Score, Mannheim Peritonitis Index, Peritonitis Index Altona II, and outcome), the intraperitoneal and the systemic inflammatory response, intraperitoneal and systemic endotoxin concentrations, and type and number of micro-organisms grown from peritoneal fluid. RESULTS: Intra-abdominal microbiological findings did not correlate with severity of illness judged by the scoring systems, the later incidence of infective complications, or the final outcome. The presence of intra-abdominal microbes was associated with signs of a systemic inflammatory response (median activation index 3 (range 1-3) compared with 2 (range 1-3)), the length of history (median 52 hours (range 3-72) compared with 16 hours (range 3-56), and local and systemic concentrations of endotoxin (peritoneal exudate: median 4800 EU/ml (range 0.06-136674) compared with 220 EU/ml (range 0.00-1800); plasma: median 0.05 EU/ml (range 0.00-1.32) compared with 0.04 EU/ml (range 0.00-0.13)). The sensitivity of the organisms to the antibiotics given (cefuroxime and metronidazole) did not influence the incidence of later infective complications or the outcome. CONCLUSIONS: These results do not suggest micro-organisms invading the peritoneal cavity and respective antibiotic treatment to be major determinants of the clinical course of peritonitis.

APACHE↗

[Therapy and follow-up of gastroesophageal chemical burns].

We report a retrospective analysis of 61 patients admitted during the years 1974 to 1992 after having recently swallowed a corrosive agent. Within 24 hours, the localisation, severity and extent of the injury had been determined by endoscopy. In 13 patients the injury was restricted to the oropharynx, and in 48 it involved esophagus, stomach and duodenum. Fourteen had sustained a second degree injury, and 16 a third degree injury. Out of five patients with third degree injuries who were treated by operation within the first three days, two survived. Two patients operated upon for complications after 10 days of conservative treatment died. The total mortality was 21%, but 56% for those who had received a third degree injury. Thirteen patients developed a stenosis (27% of those with gastroesophageal lesions). Esophageal strictures were dilatated with bougies, but stomach stenoses were treated by resection. Of the 12 patients treated by dilatation, 4 sustained perforations and 4 of them were free of symptoms for a considerable period of time (more than 4 years).

Adolescent↗

Effects of peritonitis exudates on chemotaxis and phagocytosis of human neutrophils.

OBJECTIVE: To elucidate the in vitro effects of peritoneal exudate in patients with peritonitis on the functions of normal neutrophils (chemotaxis and phagocytosis) and to correlate these findings with constituents of the exudate, severity of disease, and clinical course. DESIGN: Open study. SETTING: University hospital, Germany. SUBJECTS: Fifty consecutive patients with secondary peritonitis and healthy volunteers. INTERVENTIONS: Samples of peritoneal exudate were taken during operation and tested for their ability to stimulate or inhibit chemotaxis and phagocytosis of polymorphonuclear neutrophils (PMN). MAIN OUTCOME MEASURES: Correlation between chemotaxis and phagocytosis and concentrations of constituents of peritoneal exudate. RESULTS: Mean (SD) exudate-induced chemotaxis was 102.5 (22.8) microns compared with 62.3 (4) in the buffer control and 116 (17) in the 1 ng/ml C5a buffer control. The mean (SD) phagocytic index (uptake of zymosan and Candida albicans) was 68.8 (28.1) % of the respective serum control. There were correlations between chemotaxis and concentrations of C3a, endotoxin, and white cell count in the exudates; between phagocytosis and concentrations of C3a, IgG, IgM, protein and granulocyte elastase activity (GE and GE-alpha 1 proteinase inhibitor complex) in the peritoneal exudate; concentrations of endotoxin, and tumour necrosis factor alpha (TNF alpha), and granulocyte elastase activity in the exudate; and concentrations of C3a, IgG, IgM, and fibrinopeptide A in the exudate. There were no differences in chemotaxis and phagocytosis between patients who survived and those who died, and only the APACHE II score, the Sepsis Severity Score and the Mannheim Peritonitis Index correlated with mortality. CONCLUSION: It is still not clear whether other constituents of the exudate, variable conditions of resorption, inflammatory conditions within the peritoneal lining, or the individual patient's capacity to limit the systemic response, may have a critical role.

APACHE↗

[Enema-induced hyperphosphatemia in ileus of the small and large intestine].

We report a case of severe hyperphosphatemia following repeated use of phosphate-containing enemas in a patient with small and large bowel ileus, who died from acute renal and cardiovascular failure. Refractory hypocalcemia presumably resulted from precipitation of calcium-phosphate. Hypocalcemia may induce alterations which seriously compromise the clinical course.

Aged↗

[Surgical therapy of pancreatic carcinoma--indications and results].

Primary malignant neoplasms of the pancreas can occur as ductal adenocarcinoma in up to 80% and as a carcinoma of the exocrine or endocrine parenchyma in up to 20%. The treatment of pancreatic cancer is tumor resection. The surgical procedure depends on the tumor site: subtotal pancreatectomy, total or partial duodenopancreatectomy (Whipple's operation). The morbidity ranges from 5 to 15% and the mortality from 2 to 10%. Pancreatic carcinoma has an extremely poor prognosis, the median survival ranges from three to six months, the 5-year survival rate is 2 to 8%. These results are caused by mostly advanced tumors at the time of diagnosis. Early tumor stages with a 5-year survival rate up to 40% account for only 10% of the resected tumors; therefore, after tumor resection, recurrent disease occurs in up to 90%.

Carcinoma, Ductal, Breast↗

[Acute cholecystitis--surgical therapy].

Acute cholecystitis as a rule requires operative treatment. When it occurs as a complication of gall stone disease, early cholecystectomy within two to three days has been accepted as a safe procedure. If possible, the laparoscopic approach should be preferred. In cases of technical difficulties conventional open cholecystectomy should be planned as a primary approach or be performed by conversion of the laparoscopic approach. Cholecystostomy performed as an interventional procedure is indicated in high-risk patients due to comorbidity only. For acalculous cholecystitis, however, this approach is regarded as the initial procedure of first choice.

Acute Disease↗