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Biomedical subjects

R Obermaier

Publications and source records attributed to R Obermaier.

18 recordsLinked to original sources

[GERD: surgical therapy].

Proton pump inhibitors (PPIs) are generally accepted as gold standard for treatment of gastro-esophageal reflux disease (GERD). Nevertheless, there are clear indications for surgical anti-reflux therapy. Principally, laparoscopic anti-reflux therapy is an excellent therapeutic alternative in all patients, who have objective or subjective problems with long-term PPI therapy. Clear cut proof of the symptomatic gastro esophageal reflux (endoscopy, 24 h pH-testing) is an absolute prerequisite for surgery. Partial or total laparoscopic fundoplication has replaced completely open operative techniques. Treatment of the hiatal hernia and the hiatoplasty are integral parts of the operation. Perioperative complication rate is low. The long-term results are good. Proper patient selection and correct indication for operation are most important in this respect.

Anti-Ulcer Agents↗

Protective effect of endotoxin preconditioning in pancreas: analysis with DNA chip arrays.

Recently we demonstrated a protective effect of endotoxin preconditioning 24 hours before pancreatic ischemia-reperfusion injury, which has also been described for other organs. The mechanisms underlying this phenomenon, such as differential gene expression, are poorly investigated. We chose to approach this question by investigating differential gene expression in the rat pancreas over the time course of endotoxin pretreatment. Male Wistar rats (5 groups, 5 animals per group) were pretreated with endotoxin intraperitoneally (1 mg/kg of body weight). After treatment at 30 minutes, and at 3 and 24 hours the pancreas was removed. Untreated animals and animals with injection of saline solution served as controls. After RNA isolation, RNA was pooled and hybridized to Affymetrix chips to measure the relative mRNA levels of 7000 genes and 1000 expression sequence tags. Three hours after administration of endotoxin there was an activation of proinflammatory transcription factors and other proinflammatory genes. After 24 hours there was a clear decrease of these proinflammatory genes, but a remaining and increasing upregulation of important antiapoptotic genes, antiproteases, and other probably protective genes. There was also a significant upregulation of complement factors. It was surprising that heat-shock proteins and other typical immediate early genes of the AP-1 complex were not upregulated. Our data show that 24 hours after endotoxin stress there is a regulation of a network of genes that represents a multifaceted preconditioning. As most important factors, inhibition of apoptosis and antiproteatic strategies are identified. Heat-shock proteins seem to play no important role in the mechanism of endotoxin preconditioning.

Animals↗

Solitary fibrous tumour of the liver: case report and review of the literature.

BACKGROUND: Solitary fibrous tumours (SFTs) of the liver are very rare entities. Although firstly described to be tumours of pleural origin, SFTs have been reported in various organs such as the meninges, orbit, upper respiratory tract, thyroid, peritoneum, retroperitoneum and soft tissues. Histologically, this tumour often shows alternating cellular and relatively acellular areas. The cellular areas show a wide variety of patterns, making it difficult for it to be differentiated from other mesenchymal tumours. Its immunohistochemical positivity for CD34 and vimentin is believed to be unique. Histiogenesis of SFTs, however, is not yet fully understood. They are known to be usually benign, with only few reports indicating their ability to metastasize. PATIENTS AND METHODS: We review the literature on SFTs of the liver and report on the case of a 63-year-old female patient with a large SFT of the right liver. CONCLUSIONS: Surgical resection seems to be the treatment of choice. Local recurrence is scarce. Due to the very limited number of cases, data regarding the long-term survival of patients are lacking.

Female↗

Heterotopic pancreatitis with obstruction of the major duodenal papill--a rare trigger of obstructive orthotopic pancreatitis.

BACKGROUND: Heterotopic pancreas appears in 0.5 to 13% of autopsies. The most frequent locations are stomach, duodenum or upper jejunum. Pancreatitis in heterotopic pancreas is rarely described, and clinical symptoms caused by this heterotopic inflammation are uncommon. METHOD: We report a case of heterotopic pancreatitis localized in the major duodenal papilla causing biliary obstruction and mimicking a pancreatic head tumor. Clinically and radiologically, malignancy was suspected. Preoperative biopsies showed only fibrosis. A pylorus preserving resection of the pancreatic head was performed followed by an uneventful postoperative course. RESULT: Macroscopically, in the periampullary region on the pancreatic side a thickened duodenal wall with multiple lobules and cysts was found, compressing the common bile duct. Microscopic examination showed heterotopic pancreas with inflammatory lesions surrounding the ampulla. In the orthotopic pancreas a diffuse chronic pancreatitis with marked inflammation, fibrosis and atrophy of exocrine tissue was found. CONCLUSION: In our case it was impossible to differentiate between chronic pancreatitis and pancreas carcinoma preoperatively. Radiological findings and endoscopic biopsies were not sufficient to distinguish heterotopic pancreatitis from other tumors of the pancreatic head. Clear diagnosis could only be made by complete histological examinations after pancreatic head resection, being the treatment of choice for pancreatic head tumors of unclear dignity. The differential diagnosis of heterotopic pancreatitis as trigger of unclear enlargement of the pancreatic head is very seldom.

Cholestasis↗

Influence of nitric oxide on microcirculation in pancreatic ischemia/reperfusion injury: an intravital microscopic study.

Recently, protective effects of nitric oxide donors in pancreatic ischemia/reperfusion (IRI) injury have been described. Their role in post-ischemic microcirculation was previously not investigated. Ischemia reperfusion was induced in an isolated pancreatic tail segment in situ. Animals were randomized to four experimental groups (n=7 animals/group), the control group (CO) received saline as placebo. Treatment groups received either sodium nitroprusside (SN) 5 min before until 2 h after reperfusion, L-arginine (LA) 30 min before reperfusion until 2 h after reperfusion or sodium nitroprusside and L-arginine (SNLA) together. After induction of ischemia (2 h) post-ischemic microcirculation was observed for 2 h by intravital-fluorescence microscopy. Functional-capillary density (FCD), leukocyte adherence in post-capillary venules (LAV) and histological damage were analysed. After reperfusion FCD decreased in all groups (P<0.05). FCD was significantly restored in all groups with administration of nitric oxide donors after reperfusion (P<0.05) as compared to CO without significant difference between the individual nitric oxide donor groups. Leukocyte adherence was significantly increased 1 h and 2 h after reperfusion (P<0.001) as compared to baseline, which was lower in all nitric oxide donor groups. Histological damage in the pancreatic tail-segment was significantly reduced in nitric oxide donor groups (P<0.01). Administration of nitric oxide donors might be useful in ischemia-reperfusion injury of the pancreas by its protective effect on microcirculation and inflammatory reaction.

Animals↗

Ischemic preconditioning attenuates capillary no-reflow and leukocyte adherence in postischemic pancreatitis.

BACKGROUND AND AIMS: Ischemic preconditioning (IPC) has been shown to protect several organs from ischemia-reperfusion injury. Postischemic microvascular dysfunction is considered to be the key mechanism of early graft pancreatitis after transplantation. The aim of the study was to determine whether brief ischemia and reperfusion before prolonged ischemia followed by reperfusion is protective in respect to microcirculatory derangement in postischemic pancreatitis. METHODS: In an in-situ model of ischemia-reperfusion was induced in the isolated pancreatic tail segment. Wistar rats were randomized to one group ( n=7/group) with 2-h ischemia and reperfusion (I/R) and another group with 10-min ischemia and 10-min reperfusion (IPC) before the prolonged ischemia time. Microcirculation was observed for 2 h by intravital-fluorescence microscopy that analyzed functional capillary density and leukocyte adherence in postcapillary venules. Histological damage was quantified by a semiquantitative score (edema, vacuolization, PMN infiltration, necrosis). RESULTS: IPC resulted in a significant improvement of functional capillary density (248+/-20 vs 372+/-8 cm(-1), P<0.001), a significant reduction in leukocyte adherence in postcapillary venules (476+/-79 vs 179+/-15 cells/mm(2), P<0.001) and in significantly lower histological damage (score 9+/-0.8 vs 5+/-1.4, P<0.001), when compared with the ischemia-reperfusion group. CONCLUSION: IPC reduces pancreatic inflammatory reaction by preservation of postischemic microcirculation. Therefore, it might become a useful procedure before organ procurement in pancreas transplantation.

Acute Disease↗

Pancreas graft thrombosis: is there a role for trypsin.

PURPOSE: Thrombosis of the pancreas graft is the main cause of early graft loss in pancreas transplantation. We investigated whether hypercoagulability develops locally in the pancreas and contributes to thrombosis formation because of ischemia or reperfusion injury. It was further hypothesized that this might be induced by excessive intravascular trypsin activity. METHODS: Ten Patients undergoing pancreas transplantation were studied. In addition to the standard operation a 14 French catheter was inserted in the distal part of the splenic vein of the pancreas graft. After reperfusion blood samples were drawn simultaneously from the splenic vein of the pancreas graft (local samples) and the radial artery (systemic samples) at 0,1,2,5,10,30, and 60 minutes after reperfusion. RESULTS: After reperfusion a progressive hypercoagulability developed locally in the pancreas as seen by an increase of thrombin-antithrombin complexes and only a transient increase of plasmin-antiplasmin complexes. In addition antithrombin 3 and protein c decreased systemically. The alterations seem not to be triggered by trypsin because trypsin activity locally remained low despite trypsinogen release and activation as assessed by trypsinogen activation peptides. CONCLUSION: Local hypercoagulability might contribute to the development of graft thrombosis, however, the mechanism seems not to be related to ectopic trypsin activation.

Antithrombins↗

Value of ultrasound in the diagnosis of acute appendicitis: interesting aspects.

OBJECTIVE: The value of ultrasound in the diagnosis of acute appendicitis is still unclear. Both, studies with excellent and such with disappointing results have been published. The aim of this investigation was to answer the question, whether the results of these studies depend on study design, the investigating clinical department, or the number of ultrasound investigators. METHODS: A systematic literature research (PubMed (NLM) database) was performed. Of 99 publications dealing with ultrasound in the diagnosis of acute appendicitis, 69 were relevant to investigate the value of ultrasound in suspected appendicitis. RESULTS: Results of single-center studies (sensitivity 81.6%, specificity 89.8%, accuracy 85.7%) are better then those of multi-center trials (38.3%, 87.6%, 62.9%). There are no distinct differences between the investigating departments (surgeons 78.9%, 88.9%, 86.0%; radiologists 83.1%, 88.1%, 83.5%; mixed 77.8%, 87.1%, 79.4%, no specification 73.8%, 87.1%, 80.45.9%). Less than 10 investigators showed better diagnostic values (84.3%, 86.8%, 85.6%) compared to studies with 10 or more investigators (64.7%, 88.6%, 67.7%). CONCLUSION: The results of multi-center trials are disappointing and the good results of single-center studies do not reflect surgical everyday life. However, excellent results can be obtained if the investigation is restricted to a few specialists irrespectively of the clinical department.

Acute Disease↗

Rapamycin as rescue therapy in a patient supported by biventricular assist device to heart transplantation with consecutive ongoing rejection.

Rapamycin is a new immunosuppressive agent that has been shown to be effective in acute heart allograft rejection. This case documents a patient suffering from cardiac sarcoidosis who was bridged to transplantation for 90 days with ongoing rejection after allograft implantation. Rejection did not abate despite treatment with antithymocyte globulin (ATG), FK506, a mycophenolate switch and courses of multiple apheresis. Initiation of rapamycin treatment resulted in a rapid resolution of cardiac rejection and reduction of concomitant immunosuppressive agents with few side-effects. Most notably was the reduction of panel reactive antibodies within a few weeks after the rapamycin initiation. This case illustrates that the utilization of rapamycin ceased ongoing rejection in a patient with a clear hyperimmune state despite prior extensive utilization of a variety of immunosuppressive strategies after heart transplantation.

Adult↗

Effect of nitric oxide in ischemia/reperfusion of the pancreas.

BACKGROUND: Ischemia/reperfusion injury, and thus graft pancreatitis, remains a major problem in pancreas transplantation. Contradictory results about the role of nitric oxide (NO) in pancreatic ischemia/reperfusion have been reported; however, in none of the reports has a detailed comparison between inhibition of NO synthase and NO supplementation been carried out. METHODS: Vascular isolation of the pancreatic tail was performed in landrace pigs. After splenectomy catheters placed in the distal part of the splenic vessels allowed collection of the venous effluent and perfusion of the pancreatic tail. Three hours of complete warm ischemia was followed by 6 h of reperfusion. The effect of the NO donor sodium nitroprusside (SNP) and L-arginine was compared to a control group and NO synthase inhibition with L-NAME. RESULTS: Lipase in the venous effluent of the pancreas was significantly decreased in the SNP and the L-arginine groups. Vascular resistance was markedly elevated in the L-NAME group and reduced in the NO donor groups. Tissue pO2 after reperfusion was only significantly elevated in the SNP group. Granulocyte infiltration and also overall histological tissue injury were most severe in the control group followed by the L-NAME group, the SNP group, and the L-ARG group. CONCLUSION: The data show that supplementation of nitric oxide is clearly protective in pancreatic ischemia/reperfusion. However, inhibition of NO synthesis does not lead to an equally clear aggravation of tissue injury.

Acute Disease↗

[Successful catheter-guided local thrombolysis in acute pulmonary embolism in the early postoperative period after pancreatic head resection].

Pulmonary embolism in the early postoperative period is characterized by high morbidity and mortality. Systemic application of thrombolytic agents during this time is contraindicated; operative thrombectomy also has a high mortality rate. We report a case of successful local lysis in combination with catheter fragmentation of a massive two-sided pulmonary embolism diagnosed on the 4th postoperative day after pylorus-preserving duodenopancreatectomy for distal carcinoma of the common bile duct. Thrombolysis was performed in three sessions by a combination of catheter-supported interventional fragmentation of the thrombus with local rt-PA lysis. There were no bleeding complications or disturbances of anastomotic healing. The patient was discharged from the hospital on the 23rd postoperative day after changing anticoagulation to a vitamin K antagonist. The case presented demonstrates the possibility of local lysis in combination with interventional methods as a therapeutic option for pulmonary embolism in the early postoperative period as an alternative to surgical strategies.

Adenocarcinoma↗

Characterization of microcirculatory disturbance in a novel model of pancreatic ischemia-reperfusion using intravital fluorescence-microscopy.

INTRODUCTION: Microcirculatory disturbances caused by ischemia-reperfusion injury (IRI) are the crucial hallmarks of pancreatitis following pancreas transplantation. AIMS: To develop a novel rodent model of normothermic in situ ischemia of a pancreatic tail-segment that simulates the clinical situation of pancreas transplantation by flushing the organ via an inserted microcatheter and thus enables selective treatment of the organ via this access. METHODOLOGY: Four experimental groups were investigated (n = 7 Wistar rats/group): sham animals without ischemia and dissection of the pancreas; control animals with dissection of a pancreatic tail segment pedunculated on the splenic vessels and flushing od this segment with saline via a microcatheter; and two groups of animals treated like controls with a pancreatic ischemia time of 1 hour or 2 hours. With use of intravital epifluorescence microscopy, the microcirculatory damage was characterized by investigation of functional capillary density (FCD) and leukocyte adherence in postcapillary venules (LAV) before ischemia and during a reperfusion time of 2 hours. Dry:wet ratio determinations, light microscopy, and electron microscopic investigations were performed to characterize the histologic organ damage. RESULTS: FCD decreased significantly (p < 0.05) 2 hours after reperfusion in the groups of 1-hour (-29.21%) and 2-hour ischemia (-42.73%), in comparison with baseline values. LAV increased significantly (p < 0.05), 4.3- and 5.8-fold, after 1-hour and 2-hour ischemia during the observation time. The histologic damage was similar to posttransplantation pancreatitis in humans 1 hour after reperfusion. In sham and control animals these alterations were not significant. CONCLUSIONS: The rodent in situ model of pancreatic IRI showed standardized microcirculatory damage dependent on the ischemia time. Offering the possibility of selective treatment by the direct artery access to the ischemic pancreatic area, the model enables investigations of questions related to human pancreas transplantation.

Animals↗

Impairment of microcirculation in the early reperfusion period predicts the degree of graft pancreatitis in clinical pancreas transplantation.

BACKGROUND: Graft pancreatitis is thought to be induced by ischemia/reperfusion. Animal experiments have suggested that an impaired microcirculation is crucial in this process. We have therefore studied the relevance of microcirculation in clinical pancreas transplantation. METHODS: In 17 patients undergoing pancreas transplantation, tissue pO2 was monitored continuously by an electrode implanted into the pancreatic tail. A catheter was inserted in the distal part of the splenic vein of the pancreas graft. After reperfusion blood samples were taken from this catheter and blood flow was measured by the venous outflow method. The degree of graft pancreatitis was assessed by peak-C-reactive protein (CRP) defined as highest CRP within 3 days after transplantation. RESULTS: Tissue pO2 increased within 5 min after reperfusion. Thereafter, in most patients a transient decrease was noted, indicating impairment of nutritive perfusion. During this period there was an increasing negative correlation between peak-CRP and tissue pO2 which was highly significant at 60 min after reperfusion (r=-0.70, P<0.002). Also donor age correlated significantly with peak-CRP (r=0.64, P<0.005) and to a somewhat lesser extend with tissue pO2 60 min after reperfusion (r= -0.55, P<0.03). CONCLUSION: These data show that the degree of organ damage in clinical pancreas transplantation is directly related to an impairment of microcirculation in the early reperfusion period. These data also support the idea that grafts from older donors have a higher probability to develop graft pancreatitis and that this might be due to an increased incidence of microcirculatory disturbances in these organs.

Adult↗

Ischemia/reperfusion-induced pancreatitis in rats: a new model of complete normothermic in situ ischemia of a pancreatic tail-segment.

Ischemia/reperfusion injury plays an important role in the development of graft pancreatitis and thrombosis after pancreas transplantation. Up to now there are few therapeutic options for this severe complication because very little is known about pancreatic ischemia/reperfusion injury. The same pathomechanisms may also be involved in the induction and determination of the course of acute pancreatitis. We observed the effect of 2 h of warm in situ ischemia on the postischemic tissue oxygenation, histological organ damage, and pancreatic enzymes. Experiments were performed in 21 male Wistar rats. In sham-operated animals without ischemia, the pancreas was not dissected. In the ischemia/reperfusion group a pancreatic tail-segment was carefully separated from the head, and ischemia was induced by clamping the splenic vessels for 2 h, after flushing the pancreatic tail-segment with heparinized saline. Animals treated similarly, but with opening of the clamps some seconds after induction of ischemia, served as controls. The animals were observed for 2 h after reperfusion. Tissue oxygenation was monitored by a PO2-sensitive probe (LICOX, GMS, Kiel, Germany) which was implanted into the pancreatic tissue. Blood samples were taken before, 5 min, 60 min, and 120 min after reperfusion. At the end of the experiment the pancreatic tail was excised for histological examination; biopsies froin the non-ischemic pancreatic head served as intraindividual control to exclude side effects on the nonischemic pancreatic head. In the ischemia/reperfusion group, PO2ti was significantly lower 1 h (18.0+/-1.7 mmHg) and 2 h (16.4+/-1.6 mmHg) after reperfusion compared with baseline conditions (32.8+/-5.2 mmHg) and the control group (1 h 30.6+/-1.9 mmHg, 2 h 32.4+/-2.4 mmHg). Histological injury score and plasma lipase activity were significantly higher in the ischemia/reperfusion group compared with the control group. Thus we describe a new experimental model of complete normothermic in situ ischemia of a pancreatic tail-segment with the possibility of flushing the pancreatic tail-segment and selective local application of drugs to the pancreas.

Animals↗

Organ procurement in experimental pancreas transplantation with minimal microcirculatory impairment.

BACKGROUND: Ischemia-reperfusion injury has been shown to deteriorate microcirculation in experimental pancreas transplantation. However, minor concern was taken on the impact of organ procurement in this condition. We examined the impact of a standardized technique of organ procurement on microcirculation and apoptosis in experimental pancreas transplantation. METHODS: Male Lewis rats were divided into three groups: sham-operated animals without dissection of the pancreas served as controls (n = 5); animals undergoing nearly total process of organ procurement with the pancreas pedunculated on the aorta and the hepatoduodenal ligament (n = 7), and animals receiving pancreaticoduodenal transplantation. Pancreatic grafts were preserved for 6 h in cold University of Wisconsin solution (n = 7). At 1 and 2 h reperfusion and in time-matched controls, microcirculation was assessed by means of intravital fluorescence microscopy. Tissue samples were obtained after 2 h measurement and DNA breaks of acinar cells were detected by in situ nick end-labeling (TUNEL assay). The apoptotic index (apoptotic cells per high- power fields; hpf) was quantified by microscopic counting of at least 50 hpf. RESULTS: Assessment of functional capillary density (FCD) in animals undergoing subtotal process of organ procurement revealed a slight non-significant decrease at 1 and 2 h compared with controls. In addition, leukocyte sticking to postcapillary venules (LAV) as well as the apoptotic index were found slightly increased after organ procurement compared with controls (p > 0.05). However, after pancreas transplantation the apoptotic index and the LAV were significantly increased and the FCD significantly decreased compared with both groups of non-transplanted animals (p < 0.01). CONCLUSIONS: Our validated technique of organ procurement does not negatively impact microcirculation and apoptosis in experimental pancreas transplantation.

Anastomosis, Surgical↗

Exogenous and endogenous nitric oxide donors improve post-ischemic tissue oxygenation in early pancreatic ischemia/reperfusion injury in the rat.

INTRODUCTION: In pancreatic ischemia/reperfusion (IR) injury (IRI) the role of nitric oxide (NO) is not completely understood. Using a rat model of normothermic in situ IRI, the effect of endogenous and exogenous NO donors on post-ischemic tissue oxygenation and tissue damage was investigated. METHODS: IR was induced by 2-hour normothermic in situ ischemia of a pancreatic tail segment pedunculated on the splenic vessels with 2 h of reperfusion in an untreated, an L-arginine- and a sodium-nitroprusside-treated group (Wistar rats, n = 7/group). Animals without ischemia served as controls. Tissue oxygenation (pO(2ti)) was monitored using a pO2-sensitive Clark-type electrode. Histological investigation was performed following a semiquantitative score (edema, vacuolization, PMN infiltration, necrosis). Plasma lipase was another marker of organ damage. RESULTS: The administration of L-arginine and sodium nitroprusside caused a significant amelioration of the decrease in pO2i) after reperfusion compared to IR animals (p < 0.05). Histological damage was also reduced in the NO donor groups (p < 0.05). After reperfusion, plasma lipase in the L-arginine-treated animals was significantly lower compared to IR and sodium nitroprusside (p < 0.05). CONCLUSIONS: The administration of both endogenous and exogenous NO donors is protective in IRI of the rat pancreas which can be seen by an improvement in post-ischemic tissue oxygenation which indicates better nutritive tissue perfusion, amelioration of the histological tissue injury and, in L-arginine animals, lower lipase levels. NO donors could be useful in the prevention and reduction of the pancreatic IRI.

Animals↗