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Biomedical subjects

E Klar

Publications and source records attributed to E Klar.

At least 19 recordsLinked to original sources
PubMed1995

Isovolemic hemodilution with dextran prevents contrast medium induced impairment of pancreatic microcirculation in necrotizing pancreatitis of the rat.

BACKGROUND: Previous studies demonstrated that intravenous contrast medium (CM), as used in contrast enhanced computed tomography, aggravates the impairment of pancreatic microcirculation (PM) characteristic of severe pancreatitis and increases necrosis and mortality in necrotizing pancreatitis (NP) in rats. This study evaluates the use of isovolemic hemodilution, which can enhance the microcirculation in severe pancreatitis, for preventing CM-induced injury. METHODS: NP was induced in 30 dextran-tolerant Wistar rats by intraductal glycodeoxycholic acid and intravenous cerulein for 6 hours. PM was quantified by intravital microscopy using fluorescein isothiocyanate labeled erythrocytes. Based on previous results, areas with low blood flow (< 1.6 nL/min/cap) were identified and baseline recordings of capillary blood flow taken. A reduction of hematocrit to 75% of baseline was achieved by replacement of 5 mL/kg of blood with 25 mL/kg Ringer's lactate (RL) or by exchange of 8 mL/kg of blood for the same amount of dextran 70.6%. Thereafter, the nonionic CM iopamidol (Solutrast, Byk Gulden, Konstanz, Germany) was injected during 1 minute and PM measurements repeated after 30 and 60 minutes. RESULTS: Despite hemodilution with RL, pancreatic capillary perfusion was significantly decreased to 87% of baseline (0.83 +/- 0.04 mL/min/cap; n = 216) 60 minutes after CM infusion (P < 0.05). In contrast, capillary blood flow was significantly increased to 161% (1.56 +/- 0.05 nL/min/cap; n = 278) in the group treated with dextran. Moreover, the percentage of capillaries developing complete stasis was significantly lower in the dextran group (2.3 +/- 1.2%) compared to animals diluted with RL (22.3 +/- 4.8%) (P < 0.002). CONCLUSION: Isovolemic hemodilution with dextran prevents the additional impairment of pancreatic microcirculation induced by CM in NP.

Acute Disease↗
PubMed1995

Hyperoncotic dextran and systemic aprotinin in necrotizing rodent pancreatitis.

BACKGROUND: Dextrans improve pancreatic microcirculation in acute experimental pancreatitis. They could therefore facilitate the transport of a protease inhibitor to ischemic areas of tissue injury and be of additional benefit. METHODS: To compare the effects of dextrans with and without aprotinin, necrotizing pancreatitis was induced in 33 male dextran-resistant Wistar rats by intraductal infusion of low-dose glycodeoxycholic acid (10 mmol/l) followed by intravenous cerulein (5 micrograms/kg/h) for 6 h. Three and four hours after the start of the cerulein infusion the animals received infusions of either Ringer's lactate (RL) (12 ml/kg), 70,000 Da dextran (10%) (DEX-70) (4 ml/kg) alone, or DEX-70 (4 ml/kg) with aprotinin (5000 IU/kg) (DEX-70/A). RESULTS: The death rate was 60% within 9 h in the RL group (6 of 10) but only 10% in the DEX-70 group (1 of 10) (p < 0.03; Fisher's exact test) and 23% in the DEX-70/A group (3 of 13). Histomorphometry demonstrated a significant reduction of acinar necrosis in both treatment groups compared with control animals (p < 0.014; t test). Total amounts of trypsinogen activation peptides (TAP) in ascites were also significantly lower in these groups (p < 0.05; t test). CONCLUSIONS: DEX-70 given 3 h and 4 h after induction of pancreatitis significantly reduced the levels of TAP, limited acinar necrosis, and improved survival rate in acute necrotizing rodent pancreatitis. There was no additional benefit from the combination with aprotinin.

Acute Disease↗
PubMed1992

[Etiology and pathogenesis of acute pancreatitis].

The pathogenesis of acute pancreatitis is based on the following principles: 1. Biliary. In biliary pancreatitis there is a causal relationship between the induction of acute pancreatitis and the migration of gallstones. The basic pathomechanism seems to be a combination of an increase in permeability and pressure in the ductal system. 2. Intraacinar. Caerulein-pancreatitis is a well established experimental model which reflects the intracellular/interstitial type of activation. Basolateral secretion of pancreatic enzymes into the interstitial space represents the initial event. Intracellular activation of trypsin by the fusion of zymogen-granules and lysosomes has been advocated as an alternative mechanism. 3. Alcohol. The acute alcohol pancreatitis comprises a combined pathogenesis. Obstruction and reflux as well as the cytotoxic effect of alcohol seem to be the main principles. 4. Disturbance of pancreatic microcirculation. Ischemia of the pancreas seems to play a key role in the transition from pancreatic edema to necrosis. Improvement of capillary perfusion by isovolemic hemodilution with dextran 60 has been shown to be an efficient therapeutic tool.

Acute Disease↗
PubMed1991

Adverse effect of therapeutic vasoconstrictors in experimental acute pancreatitis.

Alpha-adrenergic drugs commonly are used to treat hypotension resulting from severe acute pancreatitis. It was shown previously that although systemic arterial pressure is increased by phenylephrine, pancreatic microcirculatory perfusion is decreased. Because inadequate tissue perfusion may be critical in the progression of edematous pancreatitis to parenchymal necrosis, it was hypothesized that vasoconstrictors might be harmful in pancreatitis. Therefore the effect of phenylephrine on cerulein-induced mild pancreatitis were studied. Sprague-Dawley rats (n = 54) were randomly allocated to 6 experimental groups and subjected to the following infusion regimens: (1) cerulein (cae) + phenylephrine (phe), (2) cae + saline (NS), (3) NS + phe, (4) cae + phenoxybenzamine (pbz) + phe, (5) NS + pbz + phe, and (6) NS. Initial and terminal hematocrit, serum amylase activity, and blood ionized calcium concentration were determined. The animals were killed 9 hours after starting the infusion. Macroscopic and histologic changes were scored by a 'blinded' pathologist. Phenylephrine increased the severity of cerulein-induced pancreatitis as manifested by statistically significant adverse changes in serum amylase, hematocrit, ionized calcium, peripancreatitic soap formation, and acinar cell vacuolization. These changes were antagonized by alpha-adrenergic receptor blockade with phenoxybenzamine. It is concluded that phenylephrine is deleterious in acute experimental pancreatitis, the first demonstration of such an effect by a pharmacologic vasoconstrictor, and suggested that microcirculatory changes may be important in the transition of mild to severe pancreatitis. Caution in the use of vasoconstrictor drugs in patients with acute pancreatitis is recommended.

Acute Disease↗
PubMed1991

[The value of classification for therapy and prognosis of acute pancreatitis. Analysis of a patient sample of the Heidelberg Surgical University Clinic 1986-1989].

116 patients admitted for acute pancreatitis were analysed. In 80% of patients presenting biliary pancreatitis cholecystectomy and bile duct exploration was the prevalent treatment, in 7.8% pancreatic necrosis was removed. Indications to operate on patients with non-biliary pancreatitis included enhancement of pancreatic inflammation revealed by computed tomography and multi-organ-failure or sepsis complicating the course of the disease (incidence of laparotomy 20.3%, incidence of necrosectomy 12.3%). According to this concept 2 out of 3 patients presenting partial pancreatic necrosis recovered without operation. Lethality of patients with acute necrotizing pancreatitis (6.9%) was accounted 25%, over-all mortality 6%. Methods used for classification of severity of acute pancreatitis (Mainz classification, Ranson criteria) turned out to be not reliable. Clinical staging of pancreatitis was not in accordance with intraoperative findings in 51.9% of cases. As a prerequisite for stage-dependent therapy new objective data to access severity and clinical course of acute pancreatitis have to be worked out.

Acute Disease↗
PubMed1990

Pancreatic ischaemia in experimental acute pancreatitis: mechanism, significance and therapy.

Much clinical and experimental evidence suggests that pancreatic ischaemia in the early phase of acute pancreatitis is important in the development of pancreatic necrosis. While depletion of intravascular volume has often been assumed to be the main circulatory defect, an additional disturbance of pancreatic microcirculation has been demonstrated experimentally. Possible contributory mechanisms include chemical-induced vasoconstriction, direct injury of vessel wall, intravascular coagulation and increased endothelial permeability resulting in pancreatic oedema, haemoconcentration and impaired venous drainage. Pancreatic ischaemia as a consequence of these local effects seems to be responsible for the transition of mild pancreatitis to parenchymal necrosis. In experimental models the beneficial effect of various drugs and of sympathetic blockade has been ascribed to an improvement in pancreatic perfusion. Although effective volume therapy is generally accepted as the mainstay of conservative treatment in acute pancreatitis, the efficacy of different fluid preparations is still controversial, and simple fluid resuscitation has not been shown to prevent the development of parenchymal necrosis. The specific impairment of pancreatic microcirculation cannot be prevented merely by replenishment of intravascular volume with crystalloids, albumin or plasma despite normalization of macrohaemodynamics. In contrast, partial replacement of blood by dextran preparations has been shown to increase pancreatic perfusion by improving blood fluidity. Isovolaemic haemodilution in conjunction with conventional fluid therapy may provide a new and effective means of protecting the pancreas from secondary injury due to the early ischaemic phase of acute pancreatitis.

Acute Disease↗
PubMed1990

Therapeutic effect of isovolemic hemodilution with dextran 60 on the impairment of pancreatic microcirculation in acute biliary pancreatitis.

Dextran of different molecular weight (Dx 40, Dx 60/70) has often been evaluated as adjunct treatment of experimental acute pancreatitis. A beneficial effect has been documented by a decrease in its lethality. However, the mechanism of action is poorly understood. A specific effect on the pancreatic microcirculation generally has not been documented and differentiation from unspecific improvement of pancreatic blood flow due to volume expansion has been difficult. This investigation was designed to quantify the effect of dextran on the impairment of pancreatic microcirculation during acute biliary pancreatitis by means of intravital microscopy. Dextran 60 (Dx 60, molecular weight 60,000) was chosen in light of the increase in vascular permeability in the early stage of pancreatitis as demonstrated previously in the same model. Isovolemic hemodilution, i.e., exchange of whole blood for Dx 60 was used as a mode of administration to achieve instantaneous onset of therapy without changes in intravascular volume. In the control group a progressive reduction of pancreatic capillary perfusion commenced 30 minutes after induction of acute pancreatitis, resulting in cessation of nutritive tissue perfusion after 3 hours. In the animals subjected to hemodilution, stabilization of the pancreatic microcirculation was accomplished throughout the observation period of 6 hours. Because volume-related effects could be excluded by the protocol and by monitoring central venous pressure and hematocrit, a specific effect of hemodilution with DX 60 on the pancreatic microcirculation is indicated by our results.

Acute Disease↗
PubMed1990

[Protein C deficiency with recurrent infarct of the small intestine].

Protein C and antithrombin III represent main inhibitors of the plasmatic coagulation system. Due to the lack of practicable assays the clinical importance of protein C was only established during the last six years. In familial protein C deficiency 77% of patients present with recurrent venous thromboses, half of them below the age of 30. In addition to recurrent superficial thrombophlebitis more serious manifestations like deep vein thrombosis and pulmonary embolism have been described. Mesenteric vein thrombosis has been reported in only 5 cases all of which could be controlled by conservative treatment. In our patient protein C deficiency was discovered 10 years after the angiographic diagnosis of portal and mesenteric vein thrombosis. Thereafter, the patient complained of recurrent abdominal discomfort. Intestinal ischaemia due to mesenteric vein thrombosis required segmental resection twice. Postoperatively the patient was heparinized. After excluding a secondary protein C deficiency due to a lack in vitamin K, hepatic disease, or disseminated intravascular coagulation, long-term anticoagulation by dicumarol was implemented as therapy of first choice.

Female↗
PubMed1990

Microcirculation of the pancreas. A quantitative study of physiology and changes in pancreatitis.

A rabbit model was designed to study the microcirculation of the pancreas with special reference to changes occurring during acute pancreatitis. Intravital microscopy was used in conjunction with video techniques allowing for continuous observation and off-line evaluation of microvessel diameters and blood cell velocities. Based on the microvessel geometry a functional microvascular unit could be defined at the level of the pancreatic lobule consisting of intralobular arteries and veins and an arcade-like preferential pathway framing the capillary network. Experimental acute pancreatitis resulted in immediate leakage of the macromolecular plasma marker (FITC-Dextran 70) from the microvasculature suggesting increased permeability. In contrast to control conditions, pancreatic capillaries were excluded from the circulation during acute pancreatitis starting 30 min after induction with only single capillaries remaining perfused after 3 hours. At the same time, there was constant blood flow through the preferential pathways representing shunt perfusion.

Acute Disease↗
PubMed1989

Clear cell sarcoma of tendons and aponeuroses: case presentation with special reference to immunohistochemical findings.

The case of a 27-year-old woman with recurring and metastasizing clear cell sarcoma (CCS) of tendons and aponeuroses is presented. Clinical setting, protracted course, and light microscopic appearance were in agreement with the original description. Immunohistologically, the tumor cells consistently expressed vimentin, S-100 protein, melanoma-associated antigens p97 and 7 kD peptide (as detected by monoclonal antibodies 96.5 and HMB-45, respectively), and major histocompatibility complex class I and (focally) class II antigens. Furthermore, the lymphocyte-associated antigen CD24 was detectable in the entire tumor cell population. Reactivity of the neoplastic cells with monoclonal antibodies to melanoma-associated antigens provides further evidence for a neural crest origin of CCS.

Adult↗
PubMed1986

[Emergency surgical indications of the colon and rectum--perforation and hemorrhage].

Colorectal perforation per se requires surgical intervention whereas in lower gastrointestinal bleeding localisation of the bleeding point has priority to any therapeutic action. Among the prevailing diagnostic methods coloscopy was found to be clinically most relevant. In profuse bleeding or for the interval detection of angiodysplasia angiography is the means of first choice. Subtotal colectomy has proved advantageous, if resection is necessitated without localisation of the bleeding site. The present operative concept in colonic perforation implies the primary excision of the lesion in diverticular as well as in neoplastic disease.

Colonic Diseases↗
PubMed1984

[Fibronectin].

Fibronectin is a dimeric glycoprotein with a molecular weight of 440,000. It is a soluble constituent of plasma and other body fluids and a fibrillar matrix protein of connective tissue. The two components are structurally similar and convertible. The possibility of multiple molecular interactions gives rise to a variety of biological functions. The regulation of cell growth and the reduced shedding of fibronectin from malignant cells raises the question as to whether fibronectin is valid as a tumour marker. In wound healing and chronic inflammation fibronectin serves as a scaffold for the formation of collagen. As opsonic protein it maintains reticuloendothelial function. Especially in shock, fibronectin may become the limiting factor of unspecific host defence mechanisms. The value of a substitution therapy will be discussed.

Animals↗