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Biomedical subjects

U Gottschalk

Publications and source records attributed to U Gottschalk.

16 recordsLinked to original sources

[Pseudoaneurysm of the left hepatic artery as a complication of ERCP with sphincterotomy].

A pseudoaneurysm of the hepatic artery is a rare complication of interventional endoscopy or transhepatic puncture. The present case report describes a symptomatic pseudoaneurysm of the left hepatic artery following endoscopic retrograde cholangio-pancreatography (ERCP). The indication was a biliary pancreatitis, and it was treated by guide-wire-sphincterotomy and extraction of sludge with a Dormia basket. A superselective angiographic embolization was not necessary because of a spontaneous thrombotic obstruction of the pseudoaneurysm.

Aneurysm, False↗

Bacterial biofilm within diseased pancreatic and biliary tracts.

BACKGROUND: Bacterial community structures in human pancreatic and biliary tracts were evaluated. METHODS: Gall bladder stones from 153 patients, 20 gall bladder walls, six common duct stones, 52 biliary stents, 21 duodenal biopsies, nine pancreatic duct biopsies, and five bile ducts were investigated using fluorescence in situ hybridisation (FISH) with ribosomal RNA targeted Cy3/Cy5 (carbocyanine) labelled oligonucleotide probes. RESULT: Duodenal, gall bladder, and bile duct walls were free of bacteria. A dense multispecies bacterial biofilm was present within the pancreatic duct of patients with calcific pancreatitis and within biliary stents, irrespective of diagnosis. The concentration, density, and amenability of the biofilm to FISH and DNA staining declined progressively with the grade of stent occlusion. The lowest detectable bacterial concentrations were found by FISH in completely occluded stents and brown/mixed gall stones. Bacteria were not detectable with FISH in cholesterol gall stones. CONCLUSIONS: A wide range of different branches and groups of bacteria participate in the development of biofilms on the surfaces of foreign bodies, such as biliary stents, mixed gall stones, or calcific pancreatic ducts, but not on the surface of pure cholesterol gall stones. Occlusion of stents leads to progressive extinction of the biofilm and mummification of its components. Deposition of cholesterol or other substances within the biofilm matrix may be a novel mechanism of host defence against bacteria present in these biofilms.

Bacteria↗

[Cyst of the common bile duct with acute abdomen].

Congenital cysts of the bile duct are well-documented anomalies of the biliary tree. Choledochal cysts frequently cause malignant changes in the epithelial lining. In such patients, the prognosis is very poor mainly because of the lack of typical symptoms in the early stages. The incidence of carcinoma in patients with bile duct cysts is estimated at 2.5 % to 15 %, compared to an incidence of 0.012 % to 0.48 % in patients without bile duct cysts. We report the case of a 32-year-old Vietnamese woman with a history of acute epigastric pain. Exploratory surgery was performed, and the segment containing the cyst and the ectopic pancreas was resected. Sonography pointed the way, and resection would have been necessary even without the abdominal symptoms.

Abdomen, Acute↗

[Intrahepatic calcification--a differential diagnostic problem].

HISTORY AND CLINICAL FINDINGS: A 57-year-old woman was admitted for investigation of intrahepatic calcifications. Intrahepatic cholangiolithiasis was suspected. In 1993 she underwent cholecystectomy because of lithiasis. The examination with endoscopic retrograde cholangiography (ERC) was planned. INVESTIGATIONS: The laboratory findings were normal except for a mild elevation of alkaline phosphatase and gammaglutamyl transpeptidase. The sonographic examination of the abdomen showed multiple hyperechoic calcifications along non-dilated bile ducts. In the spleen of normal size there were found a lot of intraparenchymatous calcifications. The abdominal roentgenography revealed calcifications also in the pancreas. In ERC, the intra- and extrahepatic bile ducts were normal with simultaneous proof of parenchymatous calcifications. TREATMENT AND COURSE: Because of the medical history of the patient and the radiologic findings the multiple parenchymatous calcifications could be referred to a miliary tuberculosis during childhood. In miliary tuberculosis, the liver almost always is involved by acute granulomatous inflammation. The therapy of hepatic tuberculosis follows the guidelines of systemic tuberculostatic therapy according to other presentations of this disease. Under sufficient therapy, tuberculotic granulomas normally heal without cicatrization. Sometimes tissue reactions in form of local fibrosis and calcification lead to a mild reduction in hepatic function as seen in this case. CONCLUSION: In the European population, intrahepatic cholangiolithiasis is a rare cause of focal hyperechoic liver lesions. In differential diagnosis, numerous diseases of possible systemic course have to be considered, which may induce calcifications of the liver or other organs. Among systemic diseases characterized by granulomatous inflammation and possible calcification tuberculosis and sarcoidosis have to be mentioned first.

Calcinosis↗

[Care of tumor patients with biliary-duodenal drainage by the family physician. Treatment of extrahepatic biliary obstruction].

Ambulatory care of patients with tumors of the biliary system and pancreas undergoing bilioduodenal drainage for obstructive jaundice is increasingly being provided by the family doctor in cooperation with an endoscopy center. The greatest risk for the patient is the development of acute cholitis caused by blockage of the endoprosthesis with the need for immediate replacement of the latter. Apart from the clinical examination, laboratory data and ultrasonography are often required to establish the diagnosis and enable an adequate assessment of the bile flow situation to be made. Additional diagnostic procedures (e.g. endosonography and computed tomography) are needed only for the primary diagnostic work-up. The data obtained from our patients show that family doctors are well attuned to the leading symptoms, and that delays in acting on suspected obstruction of the biliary stent rarely occur.

Ambulatory Care↗

[Ultrasonographic findings, diagnosis and follow-up of a rare bile duct tumor].

An 81 year old female patient developed obstructive jaundice caused by a tubular villous adenoma of the common bile duct. As her disease progressed, we diagnosed an adenocarcinoma. An endoscopically placed biliodigestive drain had to be replaced by a PTCD. The risk of malignant transformation of common bile duct adenomas is reviewed.

Adenoma, Villous↗

[Mucinous cystadenoma of the appendix].

A 63-year old female patient was admitted with a unclear abdominal ultrasound scan. Despite all our diagnostic examinations, the diagnosis--mucinous cystadenoma--was first established during surgery by intraoperative histological evaluation. We discuss the diagnostic possibilities and therapeutic approach.

Appendectomy↗

Somatic gene therapy. Present situation and future perspective.

The ultimate goal in the management of inherited as well as acquired diseases is a rational therapy with the aim to eliminate the underlying biochemical defects, rather than a symptomatic treatment. Among other approaches somatic gene therapy is a promising candidate to meet these objectives and appears to have the potential to revolutionize modern medicine. Gene therapy is characterized by the transfer of genetic information to a patient through the use of recombinant DNA technology. Several strategies for the treatment of monogenetic disorders as well as chronical diseases like cancer and AIDS have been used in various somatic gene therapy projects. So far, 329 clinical studies (phases I, I/II and II) with over 2500 patients have been initiated worldwide since 1989. No significant toxicity and adverse side effects have been observed. To allow efficient transfer of the therapeutic genes, a variety of gene delivery techniques have been developed based on viral and non-viral vector systems. For the success of this technology it is vital to achieve regulated and sustained expression of foreign genes in specific target tissues. This will be crucial for the widespread application of somatic gene therapy. So far none for the gene delivery systems is able to meet the requirements of safety, efficiency and specificity demonstrating that vector research will be an important focus in the development of optimized transfer methods. From a regulatory point of view pharmaceutical DNA-products can be regarded as drugs and are therefore subject to the same regulations. Human gene therapy must, however, be limited to manipulations affecting somatic, differentiated cells to prevent the transferred gene from being transmitted to the individual's descendants. Applications for the purpose of 'enhancement' and not for the treatment of diseases are also not acceptable. Under these prerequisites, somatic gene therapy does not raise any new ethical concerns and can be interpreted as a special form of an organ transplantation. A comparison of the different regulatory situations of gene therapy in Europe and the United States demonstrates that for the European countries a uniform regulation is desired. Today somatic gene therapy is still in its infancy. It will continue to be scientifically and technically challenging until simple and effective procedures will have been developed. Demonstration of its clinical efficacy especially in the long term will have to be the next step. Looking at the history of biotechnology and the success of the biotechnology industry that is now providing safe and efficient products from recombinant DNA-technology there is little doubt that gene therapy will become a successful treatment for various indications in the next decade. The purpose of this article is to review the current status of the development in somatic gene therapy.

Acquired Immunodeficiency Syndrome↗

Expression of natural and synthetic genes encoding herpes simplex virus 1 protease in Escherichia coli and purification of the protein.

An attractive target for anti-herpes chemotherapy is the herpes simplex virus 1 (HSV-1) protease encoded by the UL26 gene. Studies with HSV-1 strains that harbour mutations in the protease gene have demonstrated that the protease is essential for DNA packaging and virus maturation. The UL26 translation product is 635 amino acids long and undergoes autoproteolytic processing between residues Ala247/Ser248 and Ala610/Ser611. The N-terminal processing product (amino acids 1-247) contains the protease domain. To perform crystallization studies and high throughput screening for potent inhibitors, large amounts of the HSV-1 protease are required. However, expression of the natural HSV-1 protease gene in Escherichia coli using a T7-promoter-regulated system is low and does not allow for the efficient production of larger amounts of highly purified enzyme. In this report, we describe the use of a synthetic protease gene with optimized E. coli codon usage. The level of protease expression was at least 20 times higher with the synthetic gene as compared to the natural UL26 gene. The HSV-1 protease was purified to homogeneity in three steps using mixed-bed ion-exchange chromatography, affinity chromatography, and hydroxyapatite chromatography.

Amino Acid Sequence↗

A cell-surface epitope associated with liver-preferential metastasis detected by the new monoclonal antibody 3H4 in the murine tumor model ER 15-P.

In the tumor model ER 15-P, a chemically induced pleomorphic myofibrosarcoma of the C57/Bl6J mouse, cell lines with liver-preferential metastatic tumor spread were selected in vivo. In order to describe cell-surface molecules relevant for hepatic metastasis, monoclonal antibodies were raised against the liver-preferential variants. In a syngeneic immunization with viable tumor cells cyclophosphamide was used for augmentation of the humoral antitumor immunity. The monoclonal antibody mAb 3H4, an IgG2b isotype, reacted with a cell-surface epitope exclusively detected on the liver-preferential metastatic phenotype (Me) of the tumor model ER 15-P; no reactivity with the non-organ-specific metastatic phenotype (P) was observed. Regarding the morphological heterogeneity of different Me and P tumor cell populations, mAb 3H4 antigen expression was consistently associated with liver-preferential metastasis, not with different morphological stages of differentiation. It showed no cross-reaction with other tumor cell lines tested except MethA murine fibrosarcoma. The antibody was unreactive with normal tissue cells in C57/Bl6J mice. mAb 3H4 antigen expression was not dependent on the cell cycle. In an experimental assay of hematogenous metastasis, preincubation with mAb 3H4 significantly reduced the number of liver metastases of the liver-preferential tumor cells. Although no crossreaction of the primary ER 15-P with mAb 3H4 was observed, the antibody also significantly reduced the number of renal metastases of the P tumor cell population. The syngeneic IgG2b monoclonal antibody mAb 3H4 identified a new tumor-associated cell-surface antigen correlating with liver-preferential metastasis. mAb 3H4 antigen expression was a stable property of the liver-preferential tumor cells regardless of morphological diversity or functional cell status. In an in vivo blocking assay mAb 3H4 reduced liver colonization in vivo.

Animals↗

[Obstructive jaundice after granade splinter injury 49 years ago].

The present case report describes a 69 year old man who was admitted because of severe pain in the right upper abdomen by condition after a Billroth II resection of the stomach and a obstructive icterus. The reason was a common bile duct stone with a central shell splinter. Due to purulent cholangitis with inflammatory stenosis of the distal ductus choledochus endoscopic removal of the stone was only successful in repeated attempts.

Aged↗

Increased serum stability and prolonged biological half-life of neocarzinostatin covalently bound to monoclonal antibodies.

The pharmacokinetics of neocarzinostatin (NCS) have been compared to NCS conjugates with monoclonal antibodies using Balb/c and tumor bearing nude mice. Data on blood and whole body clearance revealed that the high MW conjugate persists in the body far longer and at a higher level than the free drug. Excretion of the free drug occurs with an extremely rapid renal clearance and localization of the remaining drug in the kidney, whereas the NCS immunoconjugate remained in circulation far longer allowing time for tumor localization to occur without renal accumulation of drug. In addition, NCS conjugated to monoclonal antibody was found to retain its activity in human serum better than free drug, in agreement with data obtained for other NCS-derivatives. Half-time of inactivation was greatly extended when measured under relevant conditions in a DNA strand-break assay. The results indicate that two of the most important requirements for the successful targeting of NCS in vivo, decreased clearance rate and increased serum stability are achieved by conjugation to antibody. Both results increase the probability of NCS accumulating in tissue while still in its active form. Coupling of NCS to monoclonal antibody decreases clearance and inactivation rate and increases localization of the active drug in tumor tissue.

Animals↗