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Biomedical subjects

C Herfarth

Publications and source records attributed to C Herfarth.

At least 19 recordsLinked to original sources

Detection of cytosine deaminase in genetically modified tumor cells by specific antibodies.

Bacterial cytosine deaminase (CD) converts the non-toxic prodrug 5-fluorocytosine (5-FC) into 5-fluorouracil (5-FU), which is toxic for mammalian cells. Therefore, the CD gene is used in cancer gene therapy to achieve high local concentration of a toxic metabolite without significant systemic toxicity. To allow the detection of CD expression at the protein level, we raised both polyclonal rabbit antisera and a monoclonal antibody (mAb) against a histidine-tagged CD fusion protein. The specificity of the polyclonal antisera and the mAb was confirmed by immunohistochemistry, immunoblot analysis, and immunoprecipitation using CD-expressing tumor cell lines. Furthermore, the antibodies can be used for ELISA assays and flow cytometry. Finally, the CD protein could be demonstrated in frozen tissue sections of CD-modified tumors in a rat tumor model using the anti-CD serum. With these antibodies, CD expression can now be monitored throughout in vitro and in vivo gene transfer studies, including clinical protocols relying on the CD suicide gene strategy.

Animals

[Mutations of ret-proto-oncogene in thyroid medullary carcinoma].

OBJECTIVE: To determine the importance of the molecular-genetic demonstration of germ-line mutation in the ret protooncogene for therapeutic measures in sporadic and hereditary medullary thyroid carcinoma (MTC). PATIENTS AND METHODS: Several molecular-genetic tests were performed on DNA of 35 families with hereditary and 81 patients with the sporadic form of MTC (isolation of genomic DNA; PCR amplification; DNA sequencing: demonstration of mutation in codon 918 with restriction enzyme FOK 1). RESULTS: A disease risk was demonstrated in 178 individuals among the 35 families, 159 of whom were investigated by molecular-genetic tests: 84 family members were found to be gene carriers. Germ-line mutation had already been suspected on clinical grounds in 76% of the carriers, 24% being discovered in a presymptomatic stage. Six children among the latter were treated prophylactically by thyroidectomy, histological evidence of C-cell hyperplasia being found in all of them, microcarcinomas in three of the older children. There were four patients among the non-carriers on whom thyroidectomy had been performed previously because of a false-positive pentagastrin-test; but germ-line mutation was now excluded. In one family, with familial MTC in two brothers, no mutation in ret-proto-oncogene has been demonstrated. The members of this family must now, as used to be routine, undergo a pentagastrin-test. Three of the 81 patients with "sporadic" MTC had a germ-line mutation, presumably a new one. CONCLUSION: Molecular-genetic tests have further improved the management of families with hereditary MTC and they thus take first place among essential diagnostic procedures. The diagnosis of sporadic MTC can be confirmed by excluding germ-line mutation in the ret-proto-oncogene.

Adolescent

Extrahepatic biliary obstruction impairs microvascular perfusion and increases leukocyte adhesion in rat liver.

To determine if disturbances of the liver microcirculation may be of pathophysiological relevance for liver damage during acute biliary obstruction, we studied the effects of bile duct ligation (BDL) on hepatic microhemodynamics and leukocyte adhesion in rat liver in vivo. Male Wistar rats were subjected to BDL for 3 days and 7 days, respectively. Sham-operated controls underwent laparotomy without BDL. After 3 days, intravital fluorescence microscopy (IVM) and hydrogen gas (H2) clearance were performed to study hepatic microvascular perfusion. Furthermore, leukocyte-endothelial cell interactions were assessed by IVM. Intercellular adhesion molecule 1 (ICAM-1) protein expression was studied by Western blot analysis and tissue immunofluorescence after 3 and 7 days, respectively. Analysis of microvascular perfusion by IVM revealed a marked impairment of sinusoidal perfusion after 3 days. Assessment of H2 clearance confirmed that overall hepatic microvascular perfusion was decreased. In addition, increased leukocyte adhesion in sinusoids and venules could be observed. A concomitant increase of ICAM-1 expression in liver tissue was also noted within the first week after BDL. Our results show that BDL is followed by a marked depression of the hepatic microcirculation and increased leukocyte adhesion in vivo within 3 to 7 days. Together, these findings suggest that deficits in microvascular perfusion and increased neutrophil infiltration may represent a potential source of liver injury during acute biliary obstruction.

Animals

[ICPM-independent documentation of new reimbursement forms--method and 1995 results].

The structural health care law (known as the Gesundheitsstrukturgesetz or GSG) of the Federal Republic of Germany has been enacted to replace the covering cost prices by various forms of payment. On the basis of the Godesberg Diagnosis and Therapy Catalogue, a new system has been developed that assesses all new implications of the care benefit law. With the help of intelligent plausibility tests, a particular case (PC) or a special rate (SR) is suggested. The documentation system works without ICPM numbers. The conversion of diagnosis and therapies to ICD-10/ICPM numbers is possible. The results of the first half of 1995 and the second half of 1995 show that only two-fifths of operations can be assessed with PC or SR. Neither emphasis on certain operations nor the more differentiated illnesses are recognised as extra costs by the GSG regulations. Complete and correct documentation is achieved by a strict and stratified control system.

Computer Systems

[Endosonographic diagnosis in preoperative radiotherapy of locally advanced rectal carcinoma].

Endorectal ultrasound (EUS) is important for the indication of preoperative radio(chemo)therapy of locally advanced rectal carcinomas. Preoperative radio(chemo)therapy causes an increased echogenity of the ultrasound, which histologically corresponds with increased fibrosis. After preoperative radio(chemo)therapy, the accuracy rate of EUS of tumor infiltration depth (T) and lymph-node status (N) is 75% compared with postoperative histology. With the help of EUS before and after radio(chemo)therapy (n = 28 patients) "downstaging" was noticed endosonographically in 10 patients (3 times in T and 7 times in N staging) and "upstaging" in 3 patients (3 times in T and 1 times in N staging). There was no "understaging" of local tumor infiltration depth after preoperative radio(chemo)therapy.

Adenocarcinoma

[Outcome of surgical therapy in asymptomatic primary hyperparathyroidism].

Surgery for symptomatic hyperparathyroidism remains the standard therapy. Asymptomatic primary hyperparathyroidism (pHPT) is being diagnosed with increasing frequency owing to broad serum testing. Indications for surgery in this setting are controversial. For evaluation of surgical safety we performed a retrospective analysis of our patients who were being operated on for asymptomatic pHPT. From January 1988 until August 1995, 243 patients were treated for pHPT and registered prospectively at our unit. Seventy-six patients were classified as asymptomatic. In all, 75% of the patients were female; the mean age was 62 years. In this group, 87% of the patients had cervical sonography in order to localize the adenoma. Highly selective venous catheterization was required in cervical reexplorations. Statistical analysis for potential prognostic factors for the clinical outcome was performed. Successful cervical exploration was possible in 71 patients (94.7%). With 4 patients remaining hypercalcemic, the rate of persistency was 5.2%. Localization procedures were correct in 58% for cervical ultrasound and 77% for selective venous catheterization. Postoperative morbidity included one permanent recurrent laryngeal nerve palsy and 2 patients with hemorrhage who were treated by reoperation. While one case of permanent hypoparathyroidism was well controlled by oral supplementation, 18 patients recovered from temporary hypoparathyroidism. No postoperative mortality occurred. Risk factor analysis revealed only cervical reexplorations for HPT to be associated with a higher morbidity (P = 0.02). Surgery for asymptomatic pHPT can be performed with reasonable safety. Cervical reexplorations in asymptomatic patients should be reserved for special indications. Apart from this small group, all patients should be evaluated for surgery.

Adult

[Transtracheal monitoring of the recurrent laryngeal nerve. Prototype of a new tube].

A new sensing device for the continuous intraoperative monitoring of the recurrent laryngeal nerve is presented. It is based on a double ballooned endotracheal tube including stimulating and tracing electrodes. The system is characterised by three advantages: 1) it is atraumatic, 2) it is operating completely outside the operating field (extraterritorially), 3) nerve function is being monitored continuously from the time of intubation to the time of extubation. The presented system has been evaluated in piglets. First results in humans will be available shortly.

Animals

[Significance of diagnostic imaging for determining surgical indications in solid liver tumors].

Radiological imaging is essential for the differential-diagnostic appraisal and the assessment of size, number, and localization of neoplastic liver lesions. The results determine the decision for or against operation and the surgical strategy. Moreover, oncological contraindications against surgery are recognized by imaging procedures. Technical refinements of imaging comprise improved quality of ultrasound and of computed tomography and fast sequences in magnetic resonance imaging. Special investigational protocols and specific contrast agents for ultrasonography and magnetic resonance technique are highly relevant for clinical practice. The value of diagnostic procedures is demonstrated by our own experience. The differential use of imaging procedures, technical and methodological performance and the final diagnostic interpretation require a high standard of expertise. Diagnostic accuracy is limited by technical and biological factors.

Diagnostic Imaging

[Computer-based training--a new method in surgical education and continuing education].

Computer-based training (CBT) programs teach the material of a specific field and at the same time offer various ways of objectively checking the knowledge gained. The interactive use of multimedia components, such as text, graphics, animation, sound, digital slide shows, videos and quizzes, facilitates the learning process. The aim of this study was the development and evaluation of a CBT program for use by surgeons teaching students. Using SuperCard, a teaching module for distal radius fracture (DRF) was developed, containing detailed clinical information. Video clips and vivid animation combine theoretical knowledge with practical experience. Fourth-year medical students (n = 103) were tested after using the module for 90 min. Other students (n = 47) served as the control group. In a 90-min lecture, DRF was discussed. In all evaluated criteria (distinctness, detailed description, presentation of materials, structure, motivation to learn, time saved while learning and memory retention), CBT gained 15-20% better scores than the lecture. Although 87% of the students stated that their experience with computers was limited or insufficient, 100% found the use of CBT systems helpful in student teaching. Most of them suggested the use of such programs as a exam preparation/self study method (90%) or as a supplement to a lecture (40%). Based on these evaluations, it is clear that CBT modules are an appropriate future teaching and learning system that will be well accepted. In conclusion, CBT programs should be integrated into medical education as a valuable supplement. With this aim, CBT systems should be developed and used at universities as an information system for the surgical residency program.

Achievement

[Restorative proctectomy. A comparison of direct colo-anal and colon-pouch-anal anastomoses for reconstructing continuity].

Thirty-nine of 63 patients undergoing deep anterior rectal resection received a straight coloanal anastomosis (CAA); the remaining 24 patients additionally had a colon-j-pouch (CPA) constructed. After pouch-anal anastomosis, local septic complications occurred in 12.5% of patients compared to 20.5% after coloanal anastomosis. Stool frequency after pouch-anal anastomosis was 3.3 per 24 h compared to 5.2 per 24 h after straight anastomosis within the first year after ileostomy closure (P = 0.053). Continence was slightly better in the pouch group (n.s.), and anal manometry showed a significant postoperative decrease only in resting pressure after straight colonal anastomosis (P < 0.001). This study supports the construction of a colon-j-pouch after deep rectal resection, as the pouch-anal anastomosis has fewer local septic complications and seems to improve functional outcome.

Adult

[Rehabilitation of patients with alcoholic liver cirrhosis after orthotopic liver transplantation: a 7-year follow-up].

Alcoholic liver cirrhosis is the main indication for orthotopic liver transplantation. Since 1988, 52 patients with alcoholic liver cirrhosis have been transplanted at the Department of Surgery of the University of Heidelberg. The survival rates are as follows: 73% of the patients survived for 1 year, 68% for 2 and 3 years, 64% for 4 years, and 57% survived for 5 years. After transplantation, recidivism occurred in 6 patients. Remarkable in this case was the fact that all 6 patients had a relatively short period of abstention prior to surgery (2 to 5 months). In 12 patients, a small carcinoma was found in the cirrhotic liver. This had neither been seen previously by ultrasound nor by computer tomography. In summary, orthotopic liver transplantation is an excellent mode of treatment in end-stage alcoholic liver cirrhosis. However, the patients have to be carefully selected in order to avoid recidivism following transplantation.

Adult