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E Klar

Publications and source records attributed to E Klar.

At least 73 records · Page 4Linked to original sources
PubMed2000

Influence of gastrointestinal hormones on tumor microcirculation of experimental pancreatic cancer in the rat.

BACKGROUND/AIMS: Gastrointestinal hormones influence the microcirculation in the normal pancreas. In the present study, we studied the effect of cerulein and somatostatin on pancreatic cancer microcirculation after orthotopic and nonorthotopic tumor implantation. METHODS: In 36 male Lewis rats (150-180 g) induction of a ductlike pancreatic cancer was achieved by intrapancreatic or intraperitoneal tumor fragment interposition between two inert transparent polymethyl methacrylate plates. After 4 weeks, intravital microscopy of the tumor microcirculation was performed in a temperature-controlled immersion chamber. The animals received 5 microg/kg cerulein or 3 mg/kg somatostatin for 1 h intravenously. The erythrocyte velocity in normal pancreatic capillaries or in tumor vessels was measured. RESULTS: The erythrocyte velocity in the capillaries of the normal pancreas was 1.01 +/- 0.11 mm/s at baseline and increased to 1.64 +/- 0.09 mm/s after cerulein stimulation (p = 0.007). Pancreatic cancer vessels demonstrated no increase in erythrocyte velocity after orthotopic (baseline 0.95 +/- 0.14 mm/s, after 1 h 0.86 +/- 0.13 mm/s; n.s.) and nonorthotopic tumor implantation (baseline 0.91 +/- 0.12 mm/s, after 1 h 0.95 +/- 0.14 mm/s; n.s.) after cerulein stimulation. Somatostatin decreased the erythrocyte velocity both in normal pancreas (baseline 0.87 +/- 0.02 mm/s, after 1 h 0.60 +/- 0.07 mm/s; p = 0.01) and in pancreatic cancer (baseline 0.85 +/- 0.20 mm/s, after 1 h 0.63 +/- 0.18 mm/s; p = 0.02) after orthotopic tumor implantation. There was no effect of somatostatin after nonorthotopic tumor implantation (baseline 0.90 +/- 0.10 mm/s, after 1 h 0.88 +/- 0.14 mm/s; n.s.). CONCLUSION: These data suggest that pancreatic cancer microcirculation lacks physiological blood flow control by stimulatory hormones, in contrast to the normal pancreas.

Animals↗
PubMed2000

Continuous monitoring of regional cerebral blood flow: experimental and clinical validation of a novel thermal diffusion microprobe.

OBJECT: Current clinical neuromonitoring techniques lack adequate surveillance of cerebral perfusion. In this article, a novel thermal diffusion (TD) microprobe is evaluated for the continuous and quantitative assessment of intraparenchymal regional cerebral blood flow (rCBF). METHODS: To characterize the temporal resolution of this new technique, rCBF measured using the TD microprobe (TD-rCBF) was compared with rCBF levels measured by laser Doppler (LD) flowmetry during standardized variations of CBF in a sheep model. For validation of absolute values, the microprobe was implanted subcortically (20 mm below the level of dura) into 16 brain-injured patients, and TD-rCBF was compared with simultaneous rCBF measurements obtained using stable xenon-enhanced computerized tomography scanning (sXe-rCBF). The two techniques were compared using linear regression analysis as well as the Bland and Altman method. Stable TD-rCBF measurements could be obtained throughout all 3- to 5-hour sheep experiments. During hypercapnia, TD-rCBF increased from 49.3+/-15.8 ml/100 g/min (mean +/- standard deviation) to 119.6+/-47.3 ml/100 g/ min, whereas hypocapnia produced a decline in TD-rCBF from 51.2+/-12.8 ml/100 g/min to 39.3+/-5.6 m/100 g/min. Variations in mean arterial blood pressure revealed an intact autoregulation with pressure limits of approximately 65 mm Hg and approximately 170 mm Hg. After cardiac arrest TD-rCBF declined rapidly to 0 ml/100 g/min. The dynamics of changes in TD-rCBF corresponded well to the dynamics of the LD readings. A comparison of TD-rCBF and sXe-rCBF revealed a good correlation (r = 0.89; p < 0.0001) and a mean difference of 1.1+/-5.2 ml/100 g/min between the two techniques. CONCLUSIONS: The novel TD microprobe provides a sensitive, continuous, and real-time assessment of intraparenchymal rCBF in absolute flow values that are in good agreement with sXe-rCBF measurements. This study provides the basis for the integration of TD-rCBF into multimodal monitoring of patients who are at risk for secondary brain injury.

Adolescent↗
PubMed1999

[State of the art: gastroenterologic surgery].

Microcirculation and molecular biology are the hottest topics in modern surgical research. In familial adenomatous polyposis the incidence of carcinoma can be assessed by the localisation of the PAC-gene mutation. Restorative proctocolectomy with ileoanal pouch represents the procedure of choice. The optimal age for the operation varies between 20 and 35 years according to the localisation of the mutation. RT-PCR directed to recently defined surface antigens allows for the sensitive detection of intraoperative tumor cell liberation. Due to tumor cell detection in the systemic circulation the perioperative administration of monoclonal antibodies must be advocated. A preciser definition of lymphogenic tumor spread underlines the importance of systematic lymphadenectomy in resection of the colon. The understanding of microcirculatory disorders has optimized surgical decision-making intra- and perioperatively: function of renal and hepatic microcirculation is a reliable parameter to predict graft quality already intraoperatively and to monitor therapeutic approaches to ischemia/reperfusion injury. Results in the therapy of acute pancreatitis could be improved by operating less and later. Analysis of pancreatic microcirculation resulted in an improvement of ICU-therapy in the early stages of the disease. Transplantation of the liver is limited to hepatocellular carcinoma when its localisation or the residual hepatic function after resection preclude curative excision. In addition liver transplantation should not be carried out in tumors larger than 5 cm or in patients with more than 3 tumor nodules. Liver resection for colorectal metastases is a standard procedure. A second resection of recurrent metastases is advocated since an identical median survival can be achieved compared to the primary resection (32 mo). The surgical treatment of non-colorectal liver metastases is under evaluation and should be restricted to oncological centers. Special aspects of backwashileitis in ulcerative colitis will be outlined concerning timing of colectomy, pouch construction, and follow-up.

Gastrointestinal Diseases↗
PubMed1999

Summary of the 115th annual meeting of the German Society of Surgery: Berlin, April 28 to May 2, 1998.

The annual meeting of the German Society of Surgery is equivalent to the meeting of the American College of Surgeons. More than 4800 surgeons, internists, and basic scientists gathered in Berlin. All major issues of modern surgery were addressed in 785 oral presentations and more than 270 posters with special emphasis on progress in surgical technique, transatlantic cooperation, improvement in quality management between surgery and anesthesia, and the mainstay of surgical research--microcirculation and molecular biology. The following summary conveys an impression of the current fields of reassesssment and progress in German surgery.

General Surgery↗
PubMed1999

Assessment of hepatic perfusion in pigs by pharmacokinetic analysis of dynamic MR images.

The purpose of this study was to evaluate a new method based on magnetic resonance imaging for the characterization of hepatic perfusion. In nine pigs dynamic MRI was performed before and after partial occlusion of the portal vein. The pharmacokinetic analysis of the contrast enhancement resulted in a set of parameters (amplitude, A; perfusion rate, kp; elimination rate, kappa(e1); lag time, t(lag)) of which kp was expected to correlate with hepatic perfusion. Reference measurements were done with ultrasound flow-meters and with a thermal diffusion probe (TDP). MR perfusion rate kp significantly dropped under partial portal vein occlusion from an average of 11.3 to 4.9 min(-1) (P < 0.001), while the difference in amplitude A was not significant. The correlation between kp and the TDP measurement was r = 0.89 (P < 0.001). Pharmacokinetic analysis of MRI contrast enhancement provides a non-invasive assessment of hepatic perfusion.

Animals↗
PubMed1999

Indomethacin-induced disturbances in villous microcirculation in the rat ileum.

Indomethacin is a widely used nonsteroidal antiphlogistic compound used-among others-for the treatment of rheumatoid arthritis in humans. Common side effects of indomethacin in the gastrointestinal tract include ulcerative lesions and petechial bleeding in the mucosa. In the rat, oral intake of indomethacin induces ulcerations in the mucosa of the stomach and, if administered systemically, edema, petechial bleeding, and ulcerations in the small intestine. In order to determine if systemic administration of indomethacin may induce changes in villous perfusion, we assessed the effect of indomethacin on erythrocyte velocity and the diameter of the main arteriole in the villi of the rat ileum. We found that indomethacin led to a significant decrease in mean arteriolar blood flow (6.3 +/- 0.8 vs 5.0 +/- 1.2 nl/min, means +/- SD) 7 days after administration. Mean diameter of the main arteriole remained unchanged (control, 7. 8 +/- 0.8 vs indomethacin, 7.0 +/- 0.9 microm). In conclusion, systemic application of indomethacin leads to a decrease in blood supply to the mucosa. We previously found an increase in villous perfusion when assessed 24 h after administration of indomethacin, accompanied by an increase in arteriolar diameter of the main arteriole. In summary, different regimens of application of indomethacin lead to varying observations in microcirculatory parameters in single villi. Further studies are required to identify the underlying mechanisms.

Animals↗
PubMed1999

Thermodiffusion for continuous quantification of hepatic microcirculation--validation and potential in liver transplantation.

Hepatic microcirculation is a main determinant of reperfusion injury and graft quality in liver transplantation. Methods available for the quantification of hepatic microcirculation are indirect, are invasive, or preclude postoperative application. The aim of this study was the validation of thermodiffusion in a new modification allowing long-term use in the clinical setting. In six pigs Doppler flowmeters were positioned around the hepatic artery and portal vein for the measurement of total liver blood flow. Liver perfusion was quantified by thermodiffusion and compared to H(2) clearance as an established technique under baseline conditions, during different degrees of portal venous obstruction and during occlusion of the hepatic artery. Thermodiffusion measurements were recorded for five days postoperatively followed by histological evaluation of the hepatic puncture site. Perfusion data obtained by thermodiffusion were significantly correlated to H(2) clearance (r = 0.94, P < 0. 001) and to liver blood flow (r = 0.9, P < 0.05). The agreement between thermodiffusion and H(2) clearance was excellent (mean difference -2.1 ml/100 g/min; limits of agreement -12.5 and 8.3 ml/100 g/min). Occlusion of the portal vein or hepatic artery was immediately detected by thermodiffusion, indicating a decrease of perfusion by 64 +/- 7% or 27 +/- 5% of baseline, respectively. Perfusion values at baseline and during vascular occlusion were reproducible during the entire observation period. Histological changes of the liver tissue adjacent to the thermodiffusion probes were minute and did not influence long-term measurements. In vivo validation proved that enhanced thermodiffusion is a minimally invasive technique for the continuous, real-time quantification of hepatic microcirculation. Changes in liver perfusion can be safely detected over several days postoperatively. The implication for liver transplantation has led to the clinical application of thermodiffusion.

Animals↗
PubMed1999

[The VCS clip--experimental experiences with a new vascular suture stapling device].

Despite improvements in technique and suture material, vascular anastomosis is still associated with a significant rate of early (stenosis, thrombosis) and late (intimal hyperplasia) complications. Although automatic mechanical staplers were practical und comparatively safe to use, they did not play a major role in vascular surgery, probably due to the complexity and difficult handling. In an experimental study with the VCS clip system, we found a significant improvement in performing a hepatic artery anastomosis [9.2 +/- 1.5 min (VCS) vs 20.6 +/- 2.7 min (suture), P < 0.001], early patency and flow rate [150 +/- 29.1 ml/min (1.0 h)-->79.9 +/- 24.0 ml/min (24 h) (suture) vs 186 +/- 45 ml/min (1.0 h)-->162 +/- 48 ml/min (VCS), P < 0.005]. Besides easy handling, the VCS clip system allows for a fast, standardized vascular anastomosis without intimal penetration.

Anastomosis, Surgical↗
PubMed1999

[Current management of hepatic, biliary and pancreatic trauma].

The management of hepatic trauma should be, if possible, non-operative and is initially determined by hemodynamic stability, absence of coagulopathy and limited need for blood transfusions. In hemodynamically unstable patients specific attempts to control intraparenchymal hemorrhage and resection are contraindicated. Perihepatic packing is the therapy of choice. If the hemorrhage cannot be controlled, parenchymal resection or hepatectomy with subsequent transplantation must be performed. Biliary leakage is the cause of chronic complications. The current management of intraparenchymal lesions consists of longterm drainage or stenting as combined radiological and endoscopical techniques. Pancreatic ruptures without ductal injury are treated non-operatively or by external drainage. Ductal lesions with persistent fistulas are handled depending on localization either by distal resection, pancreaticojejunostomy of the injured segment, or partial pancreaticoduodenectomy if massive disruption of the pancreatic head, duodenum or bile duct are present.

Abdominal Injuries↗
PubMed1999

Development of a computer based training program for liver transplantation.

The existence and future of every scientific area is directly and indirectly dependent on advanced education in that area and the quality of the work performed. Our aim in developing this program was to improve advanced education in liver transplant surgery and to ensure the quality of the work performed by every surgeon operating in this field. We developed a module that contains extensive information on the pathogenesis, symptoms, diagnosis, X-rays and treatment plans as well as operation-videos and case studies on the most common aspects in liver transplantation. This "teachware" is now on CD-ROM and can be installed on every personal computer without special computer knowledge. The expansion and updating of the material is technically facilitated with the help of an authoring tool.

CD-ROM↗
PubMed1999

Trypsinogen activation peptides (TAP) in peritoneal fluid as predictors of late histopathologic injury in necrotizing pancreatitis of the rat.

The levels of trypsinogen activation peptides (TAP) were quantified by ELISA immunoassay in acute pancreatitis of the rat and compared to the degree of late histopathological sequelae and exocrine functional impairment 4 and 12 weeks after the acute phase of the disease. For this purpose acute pancreatitis of different severity was induced using a suitable rat model recently described. Forty five surviving animals were studied. The level of TAP in peritoneal exudate measured 3 and 6 hr after pancreatitis induction correlated well with the amount of the late histopathological injury at the end of the corresponding observation period (at 4 weeks after 3 hr: r = 0.75, P = 0.003, after 6 hr: r = 0.72, P = 0.005, Pearson; and at 12 weeks after 3 hr: r = 0.86, P = 0.0001, after 6 hr: r = 0.84, P = 0.0001, Pearson). A negative correlation of TAP with the impairment of exocrine function was found only at 4 weeks for the secretion of total protein (r = -0.76 after 3 hr; r = -0.62 after 6 hr) and for exocrine function (r = -0.67 after 3 hr, r = -0.57 after 6 hr), but not at 12 weeks after acute pancreatitis. No correlation with plasma amylase and lipase was found. We conclude that quantitation of TAP in ascites provides an accurate prediction of late histopathologic sequelae. Pancreatic exocrine function could be predicted by TAP assay only in the early stage after pancreatitis induction (eg, four weeks). In later stages of the disease (eg, 12 weeks) remaining pancreatic tissue seems to compensate for any exocrine deficits that have occurred.

Animals↗
PubMed1999

Effect of training on the incidence of nerve damage in thyroid surgery.

BACKGROUND: In thyroid surgery early postoperative recurrent laryngeal nerve (RLN) dysfunction offers a sensitive measure of the quality of the operation. The aim of this study was to analyse the effect of training in thyroid surgery on the rate of early functional disturbances of the RLN after thyroid resection. METHODS: In 617 patients (median age 48 years, female to male ratio 2.8:1) who underwent unilateral or bilateral thyroid resection, 1059 RLNs were subjected to operative risk. Laryngoscopy was performed before and after operation. The 45 surgeons were divided into three groups: group 1, specialist thyroid surgeons; group 2, experienced surgeons; and group 3, residents. Personal gain of experience was defined by the preceding number of thyroid operations. Within each group the complication profile was determined by adding the personal complication profiles of each surgeon. RESULTS: The complication rates were low during surgical residency (group 3). In group 2 complication rates increased up to the 50th operation. Group 1 showed the expected exponential decrease to under per cent after another 130 operations. CONCLUSION: Complication rates are affected considerably by the extent of surgical experience in a non-linear and complex logarithmic manner, starting with low rates in the beginner group, peaking after further experience and then decreasing exponentially.

Adolescent↗
PubMed1999

Reduced basal and stimulated leukocyte adherence in tumor endothelium of experimental pancreatic cancer.

BACKGROUND: The interaction between immunocompetent cells and tumor endothelium is essential for an effective immunological response. In the present study, we evaluated resting and CD11b/CD18-mediated leukocyte adhesion in tumor vessels of experimental pancreatic cancer and in healthy pancreatic venules in the rat. METHODS: Solid tumor fragments (1 mm3) were interposed intrapancreatically between inert transparent polymethylmetacrylate plates for intravital microscopy (n = 12) by which tumor microcirculation, leukocyte-tumor-endothelium interaction, and the effect of the chemoattractants N-formyl-methioninleucylphenylalanine (fMLP) and platelet-activating factor (PAF) on leukocyte adherence was investigated. RESULTS: Leukocyte adhesion in pancreatic tumor vessels was significantly reduced compared to healthy pancreatic venules. Both fMLP and PAF dramatically increased leukocyte adherence in normal pancreatic venules. No change in leukocyte adhesion was present in tumor vessels after exposure to these chemotactic substances. CONCLUSION: Resting and stimulated integrin-dependent leukocyte adhesion is strongly reduced in malignant vessels of experimental pancreatic cancer, which may be an important mechanism to escape immune control.

Animals↗
PubMed1998

Effect of different immunosuppressive agents on acute pancreatitis: a comparative study in an improved animal model.

BACKGROUND: Immunosuppressive drugs have been associated with the development and progression of acute pancreatitis after organ transplantation. Consequently, a reduction or a change in immunosuppressive therapy has been recommended once posttransplantation pancreatitis has been suspected. However, it is not known which of the available immunosuppressive agents is most harmful to the pancreas and which may be used safely in this situation. The objective of this study was to investigate the effect of different immunosuppressive drugs in various dosages on intrapancreatic protease activation, acinar cell necrosis, and mortality in an improved model of acute necrotizing pancreatitis in the rat. The rat model of acute necrotizing pancreatitis, like posttransplantation pancreatitis, is characterized by ischemia and microcirculatory disorders. METHOD: Acute pancreatitis was induced in rats by using a combination of low-dose controlled intraductal glycodeoxycholic acid superimposed on intravenous cerulein hyperstimulation. Six hours thereafter, animals were randomized to intravenous therapy with 2, 10, or 50 mg/kg/day prednisolone (PRED); 3, 15, or 60 mg/kg/day cyclosporine A (CsA); 10 mg/kg/day azathioprine (AZA); 0.6 mg/kg/day orthoclone OKT3 (OKT3); or saline. After 36 hr, surviving animals were killed to determine acinar cell necrosis and trypsinogen activation peptides levels (TAP) in blood and ascites. RESULTS: Compared with saline-treated control rats, animals treated with 60 mg/kg/day CsA developed significantly more acinar cell necrosis and had increased amounts of TAP in ascites. Likewise, there was more extensive acinar cell necrosis in animals subjected to AZA therapy. However, this was not associated with incremental TAP. Animals treated with 3 or 15 mg/kg/day CsA, OKT3, or PRED showed no significant changes in these target parameters. Animals given 10 or 50 mg/kg/day PRED even had decreased hematocrit values and produced significantly less ascites than animals in the other groups. CONCLUSION: The present results suggest that AZA and high doses of CsA aggravate acute pancreatitis and should, therefore, be avoided once posttransplantation pancreatitis has been suspected, whereas lower doses of CsA, OKT3, and PRED may be used safely. PRED can even be used at higher doses as may be required when graft rejection is suspected.

Acute Disease↗
PubMed1998

Effect of surgeon expertise on the outcome in primary hyperparathyroidism.

BACKGROUND: Success in surgery for primary hyperparathyroidism (PHPT) is thought to be closely linked to surgical expertise. We investigated the effect of the surgeon's experience on the postoperative outcome in patients with PHPT. DESIGN: Cohort study with retrospective analysis. SETTING: University tertiary care center. PATIENTS: Two hundred thirty consecutive patients with PHPT. We excluded patients with prior cervical surgery, parathyroid carcinoma, multiple endocrine neoplasia types 1 and 2, and renal hyperparathyroidism. INTERVENTIONS: All 230 patients underwent bilateral neck exploration for PHPT. MAIN OUTCOME MEASURES: We registered complication rates, fulfillment of predefined operative concepts, and operative time in 230 cervical revisions for PHPT and compared the results of experienced surgeons (40 or more cervical revisions for PHPT performed before 1988) with those of surgeons still in training. RESULTS: Two surgeons classified as experienced operated on 75 patients. Under supervision of these surgeons, most operative procedures (n=155) were performed by 12 different surgeons classified as less experienced. Complications were observed in 31 patients (13.5%) with no statistical difference between the specialists and the less-experienced surgeons (P=.85). The ability to demonstrate 4 or more parathyroid glands was significantly increased for the specialists (74.7% vs 51.6%; P<.001), who also terminated the operation earlier (average, 15 minutes; P<.001). CONCLUSION: In an analysis of 230 operations for PHPT in patients without prior neck surgery, no effect of the surgeon's experience on postoperative outcome was demonstrated. Under the supervision of experienced endocrine surgeons, less-experienced surgeons perform cervical revisions for PHPT with comparable results, although with longer operating time.

Adolescent↗