Biomedical subjects

H J Buhr

Publications and source records attributed to H J Buhr.

At least 19 recordsLinked to original sources

PubMed2001

Collagen type XVIII/endostatin is differentially expressed in primary and metastatic colorectal cancers and ovarian carcinomas.

Collagen type XVIII (C18) is a nonfibrillar collagen of basement membranes. Its C-terminal fragment, endostatin, has been identified as an inhibitor of angiogenesis. C18 is predominantly expressed by hepatocytes of normal, cirrhotic and neoplastic liver. We compared the patterns of C18 RNA-expression in colonic adenocarcinoma metastases, which represent the most frequently occurring liver tumours, to normal colon mucosa, to primary colon cancers and to ovarian cancers which are often morphologically similar to colonic cancer or metastasis. Two C18-specific RNA-probes were generated to perform in situ hybridization combined with immunohistochemistry for cytokeratin, vimentin and the endothelial marker CD31, in order to characterize the C18-expressing cells. C18/endostatin protein was localized by immunohistology. In colorectal carcinomas and their liver metastases high levels of C18 transcripts were observed in endothelial cells and fibroblasts/myofibroblasts, whereas C18 RNA was virtually absent from carcinoma cells. Ovarian carcinomas displayed high C18 RNA expression both in carcinoma and stromal cells, indicating that induction of C18 transcription in tumour stromal cells is independent of the ability of carcinoma cells to express C18. While the role of tumour cell derived C18 in cancer growth regulation remains unknown, stimulation of proteolysis of the locally strongly expressed C18 to endostatin could offer an attractive approach for a targeted antineoplastic therapy.

Adenocarcinoma↗

PubMed2001

Laser-induced thermotherapy: intra- and extralesionary recurrence after incomplete destruction of experimental liver metastasis.

PURPOSE: The aim of this study was to determine the energy (J/mm3 tumor volume) and temperature required for a complete laser-induced thermotherapy (LITT) of experimental liver tumors, and to find out causes and areas of local recurrence followed by incomplete treatment. METHODS: In VX-2 tumor-bearing rabbits LITT was performed using neodymium:yttrium-aluminum-garnet (Nd:YAG) laser (1064 nm) with a diffuser-tip applicator and a temperature feedback system. The animals were randomized into four groups (n = 20) that differed in the target temperature at the tumor border as follows: 45 degrees C, 50 degrees C, 55 degrees C and 60 degrees C. The target temperature was held for 10 min constant. Histologic examination (hematoxylin and eosin [H and E], nicotinamide adenine dinucleotide phosphate [NADPH]-dehydrogenase) was performed at 0 h, 24 h, 96 h, and 14 days after LITT. RESULTS: The pretreatment tumor volume of 2191 +/- 61 mm3 was the same for all groups (p > 0.05). Energy up to target temperature and total energy required, lesion size, and the rate of incomplete tumor ablation (recurrences) are listed below (ap < 0.05, Kruskal-Wallis test). Histologically, two forms of local recurrences could be differentiated intralesionary and extralesionary. CONCLUSIONS: To achieve complete in situ ablation under the given conditions, it is necessary to apply laser energy of 3 J/mm3 tumor volume. A minimum temperature of 60 degrees C on the tumor border presumed an application of 10 min. Recurrence was found outside the coagulation zone (extralesionary) and in high vascularized areas within the coagulation zone (intralesionary).

Animals↗

PubMed2001

Continuous changes in the optical properties of liver tissue during laser-induced interstitial thermotherapy.

BACKGROUND AND OBJECTIVE: Laser-induced thermotherapy (LITT) is a promising treatment for irresectable liver tumors. To predict the effects of laser applications and to optimize treatment planning in LITT, it is essential to gain knowledge about light distribution in tissue, tissue optical properties (absorption, scattering, anisotropy, penetration depth), and their continuous changes during therapy. STUDY DESIGN/MATERIALS AND METHODS: Measurements of optical properties were performed with a double integrating-sphere system and a laser diode (830 nm). Porcine liver tissue samples were examined in a native state (35 degrees C) and after exposure to different temperatures (45 degrees C to 80 degrees C). RESULTS: Rising temperature was accompanied by a decrease in the absorption coefficient and anisotropy factor and an increase in the scattering coefficient. These changes were only significant in the temperature range of 50 degrees to 65 degrees C (P < 0.01). The optical penetration depth decreased from 3.1mm in the native state to 1.7mm at 65 degrees C (P < 0.01). Above 65 degrees, there was no significant change in the tissue optical properties. CONCLUSIONS: The optical properties of liver tissue change significantly under the influence of tissue heating, resulting in a decreased optical penetration depth. These changes occur mainly in the temperature range of 50 degrees C to 65 degrees C, corresponding to protein denaturation. To ensure a safe and effective procedure, an adjustment of the laser power to the actual penetration depth is recommended during therapy.

Animals↗

PubMed2001

Optical properties of native and coagulated porcine liver tissue between 400 and 2400 nm.

BACKGROUND AND OBJECTIVE: Laser induced thermotherapy (LITT) is a promising treatment for irresectable liver tumors. For predicting the effects of laser applications and optimizing irradiation planning in LITT, knowledge about light distribution in tissue, optical tissue properties (absorption, scattering, anisotropy, penetration depth) and their changes due to thermal denaturation is indispensable. STUDY DESIGN/MATERIALS AND METHODS: The optical parameters in healthy porcine liver were determined in the native state and after thermal coagulation using a double integrating sphere system in the wavelength range of 400-2400 nm. RESULTS: Optical parameters showed significant fluctuations in the examined wavelength range mainly due to the water and hemoglobin content in the tissue. The greatest optical penetration depth of 7.46 mm was achieved at 1070 nm. After thermal coagulation, a clear increase in scattering and a slight decrease in absorption was found, which results in a decreased optical penetration depth. CONCLUSIONS: In order to ensure a safe and effective procedure, an adjustment of the laser power to the decreasing penetration depth is recommended during therapy. These results provide a better understanding of laser-tissue interaction and may be helpful to investigators in the field of light dosimetry in liver tissue.

Animals↗

PubMed2001

An experimental rat model for studying pulmonary microcirculation by in vivo videomicroscopy.

It is unclear what role pulmonary microcirculatory disorders play in the pathogenesis of adult respiratory distress syndrome. The aim of this study was to establish a rat model for the direct visualization of pulmonary microcirculation by in vivo fluorescence videomicroscopy. The pulmonary terminal vascular bed was visualized and the microcirculatory parameters of leukocyte sticking, erythrocyte velocity, capillary permeability, and interalveolar septal diameter were quantified. These parameters were examined simultaneously. The preparation was stable for 120 min. Under hyperthermia, there was increased permeability with a relative fluorescence of 0.39 +/- 0.19 compared to 0.16 +/- 0.13 in the control group, and interalveolar septal diameters were wider (30.7 +/- 2.9 microm) than in control animals (17.3 +/- 3 microm). Under hypothermia and hypovolemia, the erythrocyte velocity was lower (0.351 +/- 0.063 and 0.378 +/- 0.044 mm/s) than in control groups (0.527 +/- 0.07 mm/s). Under hypoventilation, we observed a higher amount of leukocyte sticking (3.1 +/- 1.1 vs 1.8 +/- 0.8 cells/alveolus) and increased permeability (relative fluorescence 1.03 +/- 0.37 vs 0.16 +/- 0.13 in the control group). The model of rat lung exposure for direct examination of microvascular structures in living animals was valuable because it remained stable for 2 h under baseline conditions and demonstrated distinct changes in microcirculatory parameters following specific pathophysiological interventions.

Animals↗

PubMed2001

Serum tenascin-C is an indicator of inflammatory bowel disease activity.

Tenascin-C is a multifunctional matrix protein that is induced in inflammation and neoplasia. In the colonic mucosa of ulcerative colitis patients tenascin-C indicates tissue repair, and mucosal concentrations are correlated with local disease activity. We prospectively examined the relationship between serum concentrations of tenascin-C parameters of disease activity in surgically treated patients with ulcerative colitis and patients with inflammatory bowel disease (IBD). Perioperative serum concentrations were quantified by ELISA in 58 patients admitted for restorative proctocolectomy; controls were 37 patients with familial adenomatous polyposis receiving the same treatment. We also measured tenascin-C serum levels in 47 patients with ulcerative colitis and Crohn's disease who were receiving nonsurgical treatment. Preoperative serum tenascin-C levels were significantly higher in ulcerative colitis patients than in controls (17.2 +/- 14.6 microg/ml vs. 3.2 +/- 1.7 microg/ml) and were significantly correlated with clinical and histological parameters of disease activity; levels decreased significantly after restorative proctocolectomy. Serum tenascin-C levels were also correlated with the course of disease activity in conservatively treated IBD patients. Tenascin-C is thus not disease-specific. However, it does indicate the activity of IBD and may reflect the degree of tissue remodeling. The tenascin-C levels therefore offers a novel serum parameter for assessing disease activity and monitoring therapy in patients with IBD.

Adolescent↗

PubMed2001

Changes of colonic mucosal microcirculation and histology in two colitis models: an experimental study using intravital microscopy and a new histological scoring system.

This study investigated capillary blood flow (CBF) and pathomorphological alterations in the mucosa of different bowel segments at different times after disease onset in rats with colitis induced by either trinitrobenzensulfonic acid (TNBS) or mitomycin-C. CBF was determined by intravital microscopy using fluorescein-labeled erythrocytes. The histological degree of inflammation was assessed by a new scoring system. Severe acute histological changes were found in the distal colon 24 hr after induction of TNBS colitis (score: 8.9+/-1.0). CBF was increased (2.9+/-0.05 vs. 2.6+/-0.04 nl/min in healthy controls). The histological alterations persisted until day 3 (8.5+/-0.9) when CBF significantly decreased (1.8+/-0.05 nl/min). After 15 days, moderate acute inflammation was still detectable histologically (5.4+/-1.3), but CBF had returned to normal values. In mitomycin-C colitis, changes developed mainly in the proximal colon: After three days, there was mild inflammation (2.8+/-1.2) with normal CBF (2.5+/-0.1 nl/min). After seven days, the inflammation had increased (4.8+/-1.1), while CBF had decreased (1.5+/-0.06 nl/min). These changes persisted for six weeks (5.3+/-0.7; 1.2+/-0.05 nl/min). These data suggest that disturbed colonic microcirculation may play an important role in the pathogenesis of inflammatory bowel disease regardless of the histopathomorphological alterations.

Animals↗

PubMed2001

Activation of signal-transducer and activator of transcription 1 (STAT1) in pouchitis.

Activation of signal transducer and activator of transcription 1 (STAT1) is a hallmark of IFN-gamma receptor signal transduction but is also part of the signalling pathway of other cytokines/growth factor receptors. In ulcerative colitis, high levels of activation and expression of STAT1 have been observed in comparison with both Crohn's Disease and normal controls. Pouchitis develops in some patients after Ileal-Pouch-Anal-Anastomosis (IPAA). The pathophysiology and aetiology of pouchitis is still unclear. Recent studies have shown an increased production of proinflammatory cytokines including IFN-gamma. To investigate the expression and activation of STAT1 in pouchitis and the influence of treatment, patients were followed longitudinally from pouch operation. Diagnosis of pouchitis was made by clinical, endoscopic and histological criteria. Biopsies were obtained during routine endoscopy and snap frozen in liquid nitrogen. Nuclear and cytosolic extracts were prepared and the expression and activation of specific transcription factors were assessed by Western blot, electrophoretic mobility shift assay and immunofluorescence. Patients who develop pouchitis show highly increased levels of STAT1 alpha as well as STAT1 beta expression and activation in comparison with both normal pouch and normal ileal mucosa. Improvement of pouchitis during antibiotic therapy relates to a normalization of STAT1 expression and activation. We conclude that activation of STAT1 correlates to clinical disease activity and therefore STAT1 could play an important role in the pathophysiology of pouchitis. Similarities in the pattern of activation of STAT1 in pouchitis and ulcerative colitis may suggest a common pathway in the immunopathophysiology of both diseases.

Adult↗

PubMed2001

An improved clinical model of orthotopic pancreatic cancer in immunocompetent Lewis rats.

The study of pancreatic cancer (PaCa) requires orthotopic, clinically relevant animal models. The aims of this study were to establish an orthotopic model of ductal pancreatic adenocarcinoma in immunocompetent Lewis rats and to develop a scoring system to quantify local tumor infiltration and distant metastasis. Cells (10(7)) of the rat ductal PaCa cell line DSL-6A/C1 were injected s.c. into donor rats. After 8 weeks, either three (IPL-3) or five (IPL-5) fragments (1 mm3) of the resulting s.c. tumors were microsurgically implanted into the pancreas of recipient rats. In another series of animals, 10(7) DSL-6A/C1 cells were directly injected (INJ) into the pancreas. All animals were monitored daily until death or for 16 weeks. At autopsy, volume of primary tumors and ascites, local and systemic tumor spread, and histologic phenotype were assessed. IPL-5 resulted in significantly larger tumors (12,224 +/- 1,933 mm3), more local infiltration and systemic spread (score: 18.3 +/- 2.0 points), severe clinical tumor disease, and lethality (50%) in comparison to the other induction techniques (IPL-3: 283 +/- 115 mm3/3.5 +/- 0.8 points/0; INJ: 752 +/- 207 mm3/4.3 +/- 0.8 points/8%). Histologic examination revealed moderately to well-differentiated ductal tumors, surrounded by dense stroma. Intraperitoneal tumor dissemination in the INJ group occurred simultaneous with primary tumor growth, indicating PaCa cell spread during injection. Orthotopic implantation of five DSL-6A/C1 tumor fragments into the rat pancreas provides a valid clinical model of ductal pancreatic adenocarcinoma in immunocompetent rodents for preclinical treatment studies. The dissemination score we used permitted quantification of local and systemic tumor spread.

Adenocarcinoma↗

PubMed2001

Endothelin mediates local and systemic disease sequelae in severe experimental pancreatitis.

Endothelin-1 has been shown to reduce pancreatic blood flow and cause focal acinar cell necrosis similar to those seen in acute pancreatitis (AP), whereas therapy with endothelin receptor antagonists enhanced pancreatic capillary blood flow (PCBF) and decreased mortality rates. The current study evaluated the role of endothelin in the development of severe AP. Trypsinogen activation peptides, acinar cell necrosis, and PCBF were used as local indicators of disease severity, fluid sequestration, cardiorespiratory and renal parameters, and colonic capillary blood flow as systemic disease indicators. The following groups of animals were examined: 1) rats with mild edematous AP and 2) severe necrotizing AP treated with and without endothelin, 3) transgenic rats overexpressing endothelin with severe AP, and 4) rats with severe AP prophylactically treated with endothelin receptor antagonists. The following observations were made: endothelin superimposed on mild AP caused hemoconcentration, a decrease in PCBF, and necrosis and ascites not seen in this model without endothelin exposure. Endothelin superimposed on severe AP had no significant effects. After induction of severe AP, less PCBF and more acinar cell necrosis were observed in transgenic rats than in their normal littermates. Prophylactic endothelin receptor antagonists improved local (acinar necrosis, PCBF) and systemic parameters (ascites, urine production, colonic capillary blood flow) of disease severity in animals with severe AP. These observations underscore the role of endothelin as a mediator of disease severity in AP and suggest that endothelin receptor blockade may become a promising therapeutic tool in this disease.

Acute Disease↗

PubMed2001

Neuroendocrine differentiation is a relevant prognostic factor in stage III-IV colorectal cancer.

OBJECTIVE: To determine the prognostic relevance of neuroendocrine differentiation in colorectal cancer. METHODS: The survival of 116 patients with colorectal cancer of stages III (n = 59) and IV (n = 57) was correlated with the extent of neuroendocrine differentiation. Chromogranin A and synaptophysin were used as neuroendocrine markers. Based on the degree of immunoreactivity for these markers, tumours were classified as 0 (no expression of neuroendocrine markers), 1 (< 2% cells staining positive for neuroendocrine markers) and 2 (> 2% cells staining positive for neuroendocrine markers). Patients were followed up for more than 5 years or until death. RESULTS: Seven of 59 (11.8%) stage III cancers and 13/57 (22.8%) stage IV cancers belonged to group 2. The 96 patients of groups 0 and 1 lived for 48.9 months, whereas the 20 patients of group 2 survived for only 18.6 months (Kaplan-Meier survival curves, P < 0.001). The difference was most striking in stage III disease with 79.4 months' survival for combined groups 0 and 1, and 38.9 months' survival for group 2 (P < 0.01). Using the multivariate Cox regression model, the presence of more than 2% of cells with neuroendocrine differentiation was found to be an independent prognostic parameter for stage III and IV disease. No correlation was observed between neuroendocrine differentiation and tumour location, grade, depth of invasion or stage. CONCLUSION: Neuroendocrine differentiation is often seen in colorectal cancer. It is an independent prognostic factor in stage III-IV colorectal cancer.

Adenocarcinoma↗

PubMed2000

Expression of SIALYL-Le(x) antigen defined by MAb AM-3 is an independent prognostic marker in colorectal carcinoma patients.

Expression of mucin-bound sialyl-Le(x) antigen during the progression of colorectal carcinoma and its potential prognostic value were analysed in sections of tumours from 182 patients with a documented follow-up by immunohistochemistry using the monoclonal antibody (MAb) AM-3. Two groups of colonic carcinomas with weak (n = 79) and strong (n = 103) sialyl-Le(x) expression were discerned. The percentage of strongly expressing tumours increased with the progression of the disease (UICC stage I = 10%, stage II = 46%, stage III = 63%, stage IV = 68%, p < 0.0001). Seventy-four percent of patients with carcinomas exhibiting a strong sialyl-Le(x) expression but only 34% of patients with weak sialyl-Le(x) expression died of the disease (p = 0.0026). In multivariate analysis, strong sialyl-Le(x) expression increased the relative risk of cancer-related death 3.8-fold (95% CI = 1.8-7.9, p = 0.00034). The separate analyses of patients in UICC stage II (n = 56), III (n =5 9) and IV (n = 57) revealed that strong sialyl-Le(x) expression was associated with a reduction of the 5-year overall survival rate in UICC stage II (84% vs. 54%, p = 0.0013) and in stage III patients (86% vs. 35%, p = 0.0008) after curative resection but was not relevant in patients with distant metastases. In conclusion, the strong expression of sialyl-Le(x) antigen defined by the MAb AM-3 in colorectal carcinomas is an independent unfavourable prognostic factor after curative resection in stage II and III patients. The predictive power of the sialyl-Le(x) expression may be helpful to define subgroups of patients at high risk for whom preventive adjuvant therapy can be selectively applied before the occurrence of detectable metastases.

Adult↗

PubMed2000

Natural T-cell response against MHC class I epitopes of epithelial cell adhesion molecule, her-2/neu, and carcinoembryonic antigen in patients with colorectal cancer.

The antigens epithelial cell adhesion molecule (Ep-CAM), her-2/neu, and carcinoembryonic antigen (CEA) are potential T-cell targets in antigen-specific vaccination-based cancer therapy. We performed this study to evaluate whether a natural specific T-cell response against these tumor-associated antigens (TAAs) already exists in patients with colorectal carcinoma (CRC). We used the IFN-gamma ELISPOT assay to detect circulating TAA-reactive T cells directly ex vivo in unstimulated peripheral blood mononuclear cells. We analyzed the T-cell response in peripheral blood mononuclear cells of 22 HLA-A2-positive patients with CRC and 8 HLA-A2-positive healthy subjects against 3 HLA A2-restricted peptide epitopes of the TAAs Ep-CAM (GLKAGVIAV), her-2/neu (IISAVVGIL), and CEA (YLSGANLNL). Seven of 22 patients but none of the 8 healthy subjects had T cells specifically secreting IFN-gamma in response to one to three of these antigens (n = 4, Ep-CAM; n = 5, her-2/neu; n = 6, CEA). In three of the seven responding patients, TAA-reactive T cells were further characterized by flow cytometry. In all three patients, the majority of these T cells have a CD3+CD8+IFN-gamma+CD69+CD45RA+ phenotype, resembling activated effector-type T cells. T-cell responses occurred only in patients with metastatic disease (Dukes' stages C and D). The results of this study indicate that natural T-cell responses against TAAs occur in approximately one-half of CRC patients with involvement of lymph nodes or distant metastases, but not in CRC patients with disease confined to the intestinum.

Antibodies, Monoclonal↗

PubMed2000

Esophageal hypermotility associated with intramural pseudodiverticulosis. Primary esophageal disease or epiphenomena?

Esophageal intramural pseudodiverticulosis is a very rare disease of unclear etiology. The clinical picture is characterized by progressive dysphagia. Because of its frequent association with alcohol abuse and subsequent weight loss, it must be differentiated reliably from esophageal carcinoma. The diagnosis is established by the characteristic detection of multiple intramural contrast accumulations in the barium esophagogram. Additional endoscopic and endosonographic confirmation and histological examination are required to exclude a malignant tumor. Moreover, associated diseases are almost always present and should also be diagnosed by pH-metry, cytology, and esophageal manometry. Good and long-lasting therapeutic success can be achieved by bouginage of the stenosis with concomitant treatment of the associated esophageal diseases. Based on two case reports of patients with this disease, we discuss the unusual association with esophageal hypermotility as well as the symptoms, clinical course, therapy, and pathogenesis of the disease.

Aged↗

PubMed2000

Increased carboplatin concentration in liver tumors through temporary flow retardation with starch microspheres (Spherex) and gelatin powder (Gelfoam): an experimental study in liver tumor-bearing rabbits.

Regional chemotherapy of primary and secondary malignant liver tumors is superior to systemic therapy. The regional advantage can be further increased by flow retardation. Absorbable gelatin powder (Gelfoam) and starch microspheres (Spherex) may serve as embolizing agents because of their particle size and embolization time. Carboplatin was for the first time applied as a cytostatic agent in regional chemotherapy. Embolization and flow retardation times were measured. The embolization time of Gelfoam was 27 min, and that of starch microspheres (Spherex), 7 min, on average. Mean flow retardation of Gelfoam was 153 min, and that of starch microspheres (Spherex) 38 min. The concentration differences in systemic and regional chemotherapy were determined in VX-2 liver tumor-bearing rabbits. In regional chemotherapy, the tumor concentration was increased by a factor of 3.6 compared with systemic therapy. Coapplication with an embolizing agent increased the tumor concentration of carboplatin by a factor of 44 to 47. Concentrations of absorbable gelatin powder (Gelfoam) and starch microspheres (Spherex) did not differ significantly.

Animals↗

PubMed2000

[Topics and focuses of clinical studies in gastroenterological surgery].

High-quality clinical research offers the opportunity to exert a direct influence on medical decision-making. To take stock of the current situation in clinical gastroenterological surgery, a questionnaire was sent to 171 surgical departments focussing on visceral surgery. Of the 93 that responded, 45.2% conducted a total of 91 clinical studies. Only 8.8% of these were described as prospective randomized clinical studies; 60% were single-center studies. The studies were financed from the department budget in 60 cases, supported by industry in 27 cases and funded by independent institutions such as German Research Foundation or the Federal Ministry for Education and Research in 4 cases. Of the researchers performing the studies, 7.7% had been exempted from other duties and 92.8% were additionally involved in the clinical routine. The majority of the clinical studies in Germany deal with diseases of the esophagus and pancreas or with chronic inflammatory bowel diseases. The old and new states of the Federal Republic of Germany show no appreciable differences in the development and performance of clinical studies.

Clinical Trials as Topic↗

PubMed2000

The insertion of the lesser and greater gastric omenta and its significance for the T classification of gastric carcinomas (UICC).

The problem of T classification of proximal gastric carcinomas is becoming increasingly important due to a rise in the incidence of these tumors. The aim of this study was to examine the gastric insertion of the lesser and greater omenta and its role in the T classification of gastric carcinomas. The stomach and greater and lesser omenta were removed from 76 fixed cadavers and 12 measurements each were done in defined localizations. The lesser omentum extended to the gastric wall in 98% of the cases. This junction as well as the omental thickness and thus the retroperitoneal part are especially pronounced in the cardiac region. According to the current UICC classification, even advanced tumors extending into the gastric wall can be classified T2 as long as they do not penetrate the visceral peritoneum. This results in "understaging" and a seemingly poorer prognosis for cardiac carcinomas. Our study results support the recommendation of Hermanek and Wittekind [5] to subdivide the T2 stage of gastric carcinomas on the basis of infiltration depth.

Cadaver↗

PubMed2000

Experimental models of acute pancreatitis: are they suitable for evaluating therapy?

Since randomized controlled studies of severe acute human pancreatitis can be performed only with restrictions, at least some aspects of innovative therapy concepts should first be clarified in animal experiments. In vitro trials are inadequate for this purpose since they cannot simulate the complex course of severe acute pancreatitis. Animal test results can be transferred to clinical practice if the results are based on trials with established models, standardized methods, and a study design imitating the clinical situation. This contribution discusses the demands on such an animal model of acute pancreatitis and a corresponding study protocol and presents models and protocols which meet these requirements. Concrete examples are presented to show that animal experiments are of great value under these conditions, especially in acute necrotizing pancreatitis. Further standardization of models, protocols, and monitoring should further improve future animal therapy studies at least to the extent that it is possible to select particularly promising substances, which should then be tested in randomized controlled trials.

Acute Disease↗