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Biomedical subjects

E Klar

Publications and source records attributed to E Klar.

At least 109 records · Page 6Linked to original sources

The relative safety of MRI contrast agent in acute necrotizing pancreatitis.

OBJECTIVE: To validate the safety of gadolinium-diethylenetriamine pentaacetic acid (GD-DTPA) by measuring its effect on pancreatic capillary perfusion and acinar injury in acute pancreatitis. BACKGROUND: Contrast-enhanced computed tomography (CECT) is proposed as a gold standard for early evaluation of acute necrotizing pancreatitis. However, iodinated contrast media used for CECT have been shown in these circumstances to reduce pancreatic capillary flow and increase necrosis and mortality. Recent reports suggest that post-GD MRI provides images comparable to CECT in the assessment of severe acute pancreatitis. METHODS: Necrotizing pancreatitis was induced in 14 Wistar rats by intraductal glycodeoxycholic acid (10 mM/L) and intravenous caerulein (5 microg/kg/h) over 6 hours. Intravital microscopic quantitation of pancreatic capillary blood flow was performed using fluorescein isothiocyanate-labeled erythrocytes after induction of pancreatitis and 30 and 60 minutes after an intravenous bolus of either Ringer's solution or GD-DTPA (0.2 mL/kg). RESULTS: The two study groups were comparable with regard to mean arterial pressure, heart rate, arterial blood gases, hematocrit, amylase, lipase, and trypsinogen activation peptide production throughout the experiment. GD-DTPA did not reduce capillary flow (1.93 +/- 0.05 nL/capillary/min) compared to animals infused with Ringer's solution (1.90 +/- 0.06 nL/capillary/min). CONCLUSIONS: Intravenous injection of GD-DTPA does not further impair pancreatic microcirculation or increase acinar injury in acute necrotizing pancreatitis. Because of this advantage over CT contrast medium, further development of MRI as a staging tool in acute pancreatitis seems desirable.

Animals↗

[Effect of mast cell activation on microcirculation of intestinal mucosa in inflamed small intestine of the rat].

Intravital microscopy and FITC-labeled erythrocytes were used to investigate villous perfusion in the rat small intestine in a model of inflammatory bowel disease. Inflammation was induced with s.c. application of Indomethacin. It has previously been demonstrated that systemic Indomethacin leads to an increase in villous blood flow in the small intestine of the rat. In order to determine whether mast cell activation may contribute to the increase in villous perfusion, Ketotifen was used to inhibit mast cell degranulation. We found that Ketotifen significantly reduced villous perfusion in the inflamed intestine, but had no effect in the control group. We conclude that mast cell activation is one of the mechanisms leading to hyperemia in the mucosa of the small intestine in this animal model. Further studies are required to determine whether mast cell stabilizers may be beneficial in the treatment of inflammatory bowel disease in man.

Animals↗

[Decreasing reperfusion damage with N-acetylcysteine in experimental pancreas transplantion].

In this study we investigated the effect of donor and recipient conditioning with N-acetylcysteine on the ischemia/reperfusion injury after experimental pancreas-transplantation. We performed standardized pancreaticoduodenal transplantation in male lewis rats. The pancreas was perfused with UW-solution, harvested and conserved at 4 degrees C. Cold ischemia time was 1.5 hours and 16 hours respectively. The microcirculation in the transplanted organ was quantified by means of intravital microscopy 1.5 hours after implantation and reperfusion in the recipient. After 16 hours of cold ischemia we found a significant reduction in capillary erythrocyte velocity and a significantly enhanced leucocyte/endothelium interaction. The treatment with N-acetylcysteine resulted in a significant improvement of these microcirculatory disorders after prolonged cold ischemia.

Acetylcysteine↗

[Disorders of hepatic microcirculation as early manifestation of rejection in clinical liver transplantation].

By means of thermodiffusion, monitoring of hepatic microcirculation was performed in 43 patients during the first week after liver transplantation. A significant decrease of liver perfusion was registered in 15 patients with early rejection. The disturbance of hepatic microcirculation preceded the increase of transaminases by 36 hours and the subsequent biopsy by 60 hours. Already 12 hours after the beginning of corticoid therapy liver perfusion started to recover. The quantification of hepatic microcirculation may facilitate faster diagnosis and treatment of early rejection following liver transplantation.

Graft Rejection↗

[New aspects of anti-inflammatory potential of AT III: reduction of reperfusion injury after warm liver ischemia].

Hepatic microcirculation after warm hepatic ischemia in rats can be significantly enhanced by Antithrombin III. The number of sinusoidal stickers as a tool for characterizing the leukocyte-endothelial cell interaction was significantly reduced. The peak of serum transaminases as an indicator of hepatocellular damage was significantly decreased after the AT III application. It has to be concluded that AT III application before Pringle maneuver might significantly reduce the reperfusion damage after liver resection.

Animals↗

[Lack of stimulation of CD11b/CD18 induced leukocyte adhesioin by platelet activating factor (PAF) and f-MLP in malignant tumor endothelium in experimental pancreas cancer of the rat].

UNLABELLED: The interaction between immunocompetent cells and tumor-endothelium is essential for effective immunologic recognition. In the present study we evaluated resting and CD11b/CD18-mediated leukocyte adhesion on tumor-endothelium of experimental pancreatic carcinoma and in healthy pancreatic venules. METHODS: 22 male Lewis rats (120-140 g) were anesthetized. Duct-like pancreatic carcinoma (DSL6A, Am. J. Pathol. 1993; 143:292) was induced by intrapancreatic implantation of tumor fragments between inert polymethylmetacrylat plates. After 4 wks the tumor-bearing pancreas was exposed and the microcirculation studied. Parameters in tumor vessels (15-40 microns) and healthy pancreatic collecting venules (20-40 microns) included: Erythrocyte velocity, Leukocyte adhesion, Vessel diameter and wall shear rate. Measurements were obtained before and 5 min after adding f-MLP (100 mM) or PAF (50 mM), two CD11b/CD18 agonists of different potency to the immersion chamber. RESULTS: [table: see text] CONCLUSION: In experimental pancreatic carcinoma leukocyte adhesion of low affinity is reduced despite comparable wall shear rates. The CD11b/Cd18-mediated adhesion of high affinity, which is inducible by f-MLP and PAF in healthy pancreatic venules, is absent in tumor vessels. This may be a mechanism by which malignant tumors escape immune control.

Animals↗

[Experimental evaluation of dynamic MRI for quantifying liver perfusion].

Gadolinium-DTPA enhanced dynamic MR imaging is a new method for the quantification of portal bloodflow and liver perfusion. In this study we evaluated the validity of this method comparing it with thermodiffusion and dopplerflowmetry in pigs. We found a significant correlation of tissue perfusion between dMRI and thermodiffusion and of portal bloodflow between dMRI and dopplerflowmetry. Partial occlusion of the portal vene was accurately detected by dMRI. Dynamic MRI could become a valuable diagnostic method for the quantification of liver perfusion.

Animals↗

[Reduction of local and systemic complications of acute pancreatitis by monoclonal antibody to ICAM-1].

The prognosis of acute necrotizing pancreatitis is dependent on systemic complications. The endothelial adhesion molecule ICAM-1 mediates both leukocyte adhesion and migration. Expression of ICAM-1 was investigated at various time points in mild and severe necrotizing pancreatitis in the pancreas, lungs and intestine. A possible therapeutic effect of monoclonal antibodies against ICAM-1 was evaluated in severe necrotizing disease. The expression of ICAM-1 preceded the fulminant leukocyte Infiltration of the organs. In contrast to mild pancreatitis, ICAM-1 expression was increased at an earlier time point and systemically in severe necrotizing disease. Treatment with antibodies against ICAM-1 improved microcirculation and reduced local and systemic organ damage in severe pancreatitis.

Animals↗

[Understanding microcirculation deficits as the key to surgical planning in visceral surgery].

It was the aim of our investigation to analyse microcirculatory disorders in order to optimize surgical decision-making intra- and perioperatively. Acute pancreatitis: The surgical principle to operate less and later is based on an improved ICU therapy. Using intravital microscopic quantification of pancreatic microcirculation it could be shown experimentally that in the early phase pancreatic necroses can be limited by improvement of pancreatic microcirculation. Hemodilution with dextran is superior to other regimens. Liver resection: The expansion of liver resections requires a reduction of ischaemia/reperfusion injury. Preconditioning of the liver, i.e. induction of short-term ischaemia prior to the main ischaemic period, results in an induction of protective mechanisms with increased tolerance to ischaemia. Liver transplantation: Liver microcirculation is a reliable parameter to predict graft quality intraoperatively and to monitor therapeutic approaches to ischaemia/reperfusion injury. With the analysis of microcirculatory disorders, a basic understanding for organ dysfunctions which lead to operation or are a result of surgical therapy can be gained.

Animals↗

Typical experiences of a former research fellow in the USA.

Besides personal experience as a former research fellow, the prerequisites for a successful research fellowship in the USA were analysed. Individual initiatives without any infrastructure for successful reintegration at home will fail. Isolated publications will carry the insignia of the guest university without providing benefit for the home institution at a later stage. The ideal constellation is the continuity of international cooperation in combination with an active research group at home. In addition to the respective publications, the following achievements of a research period in the USA can be attained: Establishing ongoing contacts to an international research group in the own field of interest; training in "how to write a scientific paper"; introduction to the "international scientific community". The potential contact to other groups cannot be planned, but represents an important aspect of a research period. To learn to appreciate other peoples' way of living adds to the personality of every scientist.

Fellowships and Scholarships↗

[Development of a computer-assisted learning program for liver transplantation].

The German Society for Surgery recently decided to rename the "video library" as a "multimedia library", which will include also interactive, nonlinear computerised teachware in surgery. We report on the complex interaction of authors, editor, and the computer-based training laboratory, and the pitfalls with respect to data collection, structure, implementation, and technical aspects of the CD-ROM liver transplantation.

Computer-Assisted Instruction↗

[Effect of primary surgical therapy on the course of C-cell carcinoma of the thyroid gland].

The effect of the type of initial surgery for medullary thyroid carcinoma on the outcome is obscure. Some 40 patients with hereditary medullary thyroid carcinoma underwent either thyroidectomy and modified radical neck dissection (n = 18), subtotal thyroid resection (n = 10), or thyroidectomy (n = 12), partly with selective lymphadenectomy, as initial surgery. Patients who underwent thyroidectomy and modified radical neck dissection as their first operation had higher cure rates and lower morbidity. Thus the initial procedure is decisive for the further outcome in patients with hereditary medullary thyroid carcinoma.

Adolescent↗

[Continuous monitoring of the recurrent laryngeal nerve].

A new "all in one" sensing device for tracing and continuous intraoperative monitoring of the recurrent laryngeal nerve during thyroid surgery is described. The system, based on a double ballooned endotracheal tube, is atraumatic, easy to use and sensitive even to imminent trauma to the nerves. The most striking feature of this instrument is that it operates outside the sterile operating field and truly monitors continuously throughout the operation.

Adult↗

[Chronic liver immunologic factors in ischemic type biliary lesions (ITBL) --> reduced Th1 and increased Th2 response].

Compared to patients with a stable liver function, we found a decreased Th1 and increased Th2 response in patients presenting with ischemic type biliary lesions following liver transplantation. It remains open to speculation whether these immunological changes were induced by the damage of the bile ducts, occur as an additional damaging factor or are found as an epiphenomenon in patients with liver transplant dysfunction.

Bile Ducts↗

Continuous measurement of porcine renal cortex microcirculation with enhanced thermal diffusion technology.

Continuous monitoring of renal cortical blood flow (RCBF) in the perioperative setting of aortic or renal vascular surgery could facilitate the early detection of vascular complications, possibly resulting in a reduction of postoperative renal failure. A new prototype system for measurement of parenchymous organ perfusion based on the principle of thermal diffusion ("TD"-Thermal Diffusion Electrode, Thermal Technologies Inc., Cambridge, MA, USA) was used for RCBF measurements in the outer cortex of the porcine kidney. We validated the sensitivity of the device to detect renal blood flow impairment, comparing TD flow data with renal artery blood flow values (RABF), measured by ultrasonic flow probes. The hypothesis was tested that acute disturbances of RCBF, induced by a variable degree of renal artery stenosis, can be immediately detected and continuously monitored by TD measurements in the porcine renal cortex. Mean baseline RCBF measured by TD electrodes was 68.1 +/- 25.0 ml/100 g/min. Mean baseline RABF was 102.1 +/- 26.6 ml/min. Controlled induction of a variable degree of renal arterial occlusion by implanted vascular balloon occluders was always followed by an immediate and proportional decline of RCBF, as measured by TD. Flow data obtained with both methods were significantly correlated by linear regression (r=.82, r2=.68; P < 0.0001). Dynamic changes of RABF in the time course of renal artery partial/total occlusion and arterial flow release could be continuously followed by detection of corresponding flow changes of RCBF. We conclude that the TD system investigated in the current study allows a continuous and sensitive determination of porcine renal cortex perfusion. A clinical evaluation of the method, e.g., in the perioperative setting of aortic or renal transplantation surgery, now appears to be justified.

Animals↗

First clinical realization of continuous monitoring of liver microcirculation after transplantation by thermodiffusion.

To date, no method is available for the continuous long-term monitoring of liver microcirculation in patients. Experimentally, thermodiffusion has been validated in the quantification of hepatic perfusion. In an attempt to investigate the practicability of thermodiffusion technology in patients after liver transplantation thermodiffusion probes were inserted into the graft in seven patients during liver transplantation. Continuous monitoring started intraoperatively and was performed until day 7, when the probes were extracted transcutaneously. No probe-related complications (i.e., hemorrhage, infection) were observed. In four patients with normal graft function, liver perfusion recovered within 12 h from the intraoperative reduction to a range between 85 and 93 ml/100 g per min. In contrast, primary graft failure (n = 1) was characterized by a constant decrease of hepatic perfusion (< 50 ml/100 g per min). In prolonged reperfusion injury (n = 1), a second peak of transaminases was paralleled by an impairment of liver microcirculation. In one patient, R2 rejection on day 7 was preceded by a drop in hepatic perfusion 48 h earlier. Thus, thermodiffusion is a safe and reliable method for the continuous quantification of liver microcirculation after transplantation in patients. Measurements are reproducible for at least 7 days. Changes in hepatic perfusion during postoperative complications can be detected. The characteristics of microcirculatory disorders will have to be defined in a larger number of patients.

Adolescent↗