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Biomedical subjects

L Fischer

Publications and source records attributed to L Fischer.

At least 55 records · Page 3Linked to original sources
PubMed2000

The impact of 3-dimensional reconstructions on operation planning in liver surgery.

BACKGROUND: Operation planning in liver surgery depends on the precise understanding of the 3-dimensional (D) relation of the tumor to the intrahepatic vascular trees. To our knowledge, the impact of anatomical 3-D reconstructions on precision in operation planning has not yet been studied. HYPOTHESIS: Three-dimensional reconstruction leads to an improvement of the ability to localize the tumor and an increased precision in operation planning in liver surgery. DESIGN: We developed a new interactive computer-based quantitative 3-D operation planning system for liver surgery, which is being introduced to the clinical routine. To evaluate whether 3-D reconstruction leads to improved operation planning, we conducted a clinical trial. The data sets of 7 virtual patients were presented to a total of 81 surgeons in different levels of training. The tumors had to be assigned to a liver segment and subsequently drawn together with the operation proposal into a given liver model. The precision of the assignment to a liver segment according to Couinaud classification and the operation proposal were measured quantitatively for each surgeon and stratified concerning 2-D and different types of 3-D presentations. RESULTS: The ability of correct tumor assignment to a liver segment was significantly correlated to the level of training (P<.05). Compared with 2-D computed tomography scans, 3-D reconstruction leads to a significant increase of precision in tumor localization by 37%. The target area of the resection proposal was improved by up to 31%. CONCLUSION: Three-dimensional reconstruction leads to a significant improvement of tumor localization ability and to an increased precision of operation planning in liver surgery.

Computer Simulation↗
PubMed2000

Identification of fluorine sites at the surface of fluorinated gamma-alumina by two-dimensional MAS NMR.

By means of 27Al triple quantum Magic-Angle Spinning Nuclear Magnetic Resonance (3QMAS NMR) and 27Al[19F] WISE MAS NMR, we were able to detect three different Al-F sites on the surface of fluorinated gamma-alumina. Three 19F resonances at 9, 20, and 33 ppm (from C6F6) correlated to 27Al resonances in the octahedral range. While the positions of the maxima in the 27Al dimension were ill-defined due to the inherently low efficiency of the 27Al[19F] CPMAS process, the center of gravity of the lines shifted significantly upfield in that dimension with increasing wt.% F. Tentatively, these three resonances were assigned to (VI)Al(O(6-n)Fn) (n = 1, 2, 3) environments on the F/gamma-Al2O3 surface. At F contents above levels corresponding to the full fluorination of the gamma-Al2O3 surface, neoformation of an AlF3 x 3H2O phase was also evidenced with an 19F resonance at -8 ppm and with an 27Al resonance at -17 ppm.

Aluminum Compounds↗
PubMed2000

Cellular interactions and signaling in cartilage development.

The long bones of the developing skeleton, such as those of the limb, arise from the process of endochondral ossification, where cartilage serves as the initial anlage element and is later replaced by bone. One of the earliest events of embryonic limb development is cellular condensation, whereby pre-cartilage mesenchymal cells aggregate as a result of specific cell-cell interactions, a requisite step in the chondrogenic pathway. In this review an extensive examination of historical and recent literature pertaining to limb development and mesenchymal condensation has been undertaken. Topics reviewed include limb initiation and axial induction, mesenchymal condensation and its regulation by various adhesion molecules, and regulation of chondrocyte differentiation and limb patterning. The complexity of limb development is exemplified by the involvement of multiple growth factors and morphogens such as Wnts, transforming growth factor-beta and fibroblast growth factors, as well as condensation events mediated by both cell-cell (neural cadherin and neural cell adhesion molecule) and cell-matrix adhesion (fibronectin, proteoglycans and collagens), as well as numerous intracellular signaling pathways transduced by integrins, mitogen activated protein kinases, protein kinase C, lipid metabolites and cyclic adenosine monophosphate. Furthermore, information pertaining to limb patterning and the functional importance of Hox genes and various other signaling molecules such as radical fringe, engrailed, Sox-9, and the Hedgehog family is reviewed. The exquisite three-dimensional structure of the vertebrate limb represents the culmination of these highly orchestrated and strictly regulated events. Understanding the development of cartilage should provide insights into mechanisms underlying the biology of both normal and pathologic (e.g. osteoarthritis) adult cartilage.

Body Patterning↗
PubMed2000

Metastatic calcification in a dog attributable to ingestion of a tacalcitol ointment.

A 22-week-old 21-kg female Bernese Mountain Dog ingested a topical antipsoriatic preparation containing the synthetic vitamin D analog tacalcitol. The dog died after a history of lethargy, recumbency, paresis of the hindlimbs, increased rectal temperature, dyspnea, and hematemesis. Histologic examination revealed metastatic calcification in the kidneys, lungs, myocardium, brain, stomach, and tear glands. The appearance of soft tissue mineralization in multiple organs is consistent with hypercalcemia derived from excessive vitamin D uptake. Oral toxicity studies for tacalcitol in the dog are not available, but the present report emphasizes the extraordinary toxic risk of drugs containing this vitamin D analog to dogs.

Animals↗
PubMed2000

Mycophenolate mofetil for prevention of liver allograft rejection: initial results of a controlled clinical trial.

UNLABELLED: Mycophenolate Mofetil (M MF) is a new immunosuppressive agent with proven efficacy for the prevention of kidney allograft rejection. However, only little experience is available with the use of MMF in liver transplant recipients. OBJECTIVES: In this prospective, controlled trial the efficacy and safety of MMF and Azathioprine (AZA) were compared in a Neoral based quadruple immunosuppressive regimen after orthotopic liver transplantation. METHODS: Between 12/96 and 12/98 57 adult patients were enrolled in the study at the University of Hamburg. 28 patients were randomised to MMF, 29 patients to AZA in combination with equivalent doses of lymphocyte antibodies, Neoral and methylprednisolone. RESULTS: After a median follow-up of 10+/-3.2 months patient or graft survival did not differ significantly between the MMF and AZA group. However, MMF treated patients experienced less frequently acute rejection episodes (MMF: 6/28; 21.4% versus AZA: 13/29; 44.8%) (p=0.06). Furthermore, thrombocytopenia (MMF: 6/28; 21.4% versus AZA: 14/29; 48.3%) (p<0.05) and leukopenia (MMF: 2/28; 7.1% versus AZA: 6/29; 20%) (p=0.14) were less often observed under MMF compared to AZA. The incidence of serious bacterial infections and cytomegalovirus infections was almost identical in both groups. These preliminary data suggest that after liver transplantation primary immunosuppression with MMF is advantageous over AZA with regard to safety and efficacy.

Adult↗
PubMed2000

Therapeutic angiogenesis for ischemic syndromes.

Disease caused by atherosclerosis are the most common causes of morbidity and mortality in western societies. The inadequacy of current therapeutic modalities is most pronounced in the significant proportion of patients with arterial obstructive disease, in whom anatomical and technical limitations rule out the possibility of angioplasty or surgery. Therefore, less invasive approaches are necessary to treat these patients. The development of collateral circulation improves blood flow to ischemic tissues and to alleviate ischemia-related symptoms. Our project concentrates on enhancement of the natural mechanism of angiogenesis by adenoviral based vector encoding vascular endothelial growth factor as an angiogenic factor. The aim of our study was to determine the efficacy of human vascular cell infection by adenoviral based vectors in vitro and in vivo. Human saphenous vein endothelial cells and smooth muscle cells were infected by adenoviral vectors encoding the lacZ and VEGF genes (rAdlacZ, rAdVEGF). VEGF expression by adenoviral vector-infected cells was detected by western analysis and its biological activity was examined by proliferation assay. The feasibility of adenoviral based gene transfer in vivo was evaluated after direct femoral artery injection of rAdlacZ in the rat. Vascular endothelial and smooth muscle cells expressed high levels of VEGF following rAdVEGF infection. The mitogenic effect of VEGF was validated by threefold increase in EC proliferation rate in comparison to the control groups. In vivo gene transfer was demonstrated using lacZ gene transfer to arterial wall cells in the superficial femoral artery. Efficient adenoviral based gene delivery was demonstrated both in vitro and in vivo. VEGF over-expression enhanced endothelial cell proliferation, which is the key step for induction of angiogenesis.

Adenoviridae↗
PubMed1999

[Examining the shoulder in general practice].

When the cause of pain or the loss of function lies in the shoulder area itself, in most cases it can be related to a certain anatomical structure by means of a precise clinical examination. The individual tests are depicted in illustrations and concise texts. As a memory aid, the structure being tested has been added in each picture. Also, the clinically most relevant trigger points are depicted, along with their corresponding pseudoradicular symptomatology (referred pain). The aim of this article is to assist in the day-to-day treatment of common shoulder problems.

Diagnosis, Differential↗
PubMed1999

Enhanced protective response and immuno-adjuvant effects of porcine GM-CSF on DNA vaccination of pigs against Aujeszky's disease virus.

This study was conducted to investigate whether the co-delivery of DNA encoding porcine cytokines would enhance a protective immune response in pigs to a Pseudorabies virus (PRV; or Aujeszky's disease virus) DNA vaccine. Aujeszky's disease in pigs results in respiratory and nervous symptoms with important economic losses. To evaluate cytokine effects, eukaryotic expression vectors were constructed for porcine GM-CSF, IL-2 and IFN-gamma. cDNA for each of these cytokines was inserted under the control of a CMV promoter in the pcDNA3 plasmid and cytokine expression was confirmed after DNA transfection in various mammalian cell cultures by bioassays (GM-CSF and IL2) and ELISA (IFN-gamma). Pigs were vaccinated by single intramuscular injection with plasmid DNA encoding PRV gB and gD along with various combinations of cytokine plasmid constructs. Pig serum was tested for the production of antibody by isotype specific anti-PRV ELISA. Pigs were then challenged with the highly virulent PRV strain NIA3 on day 21 after vaccination. The survival and growth rate of pigs were monitored for seven days after the viral challenge. The co-administration of GM-CSF plasmid increased the immune response induced by gB and gD PRV DNA vaccine. This immune response was characterized by an earlier appearance of anti-PRV IgG2, a significantly enhanced anti-PRV IgG1 and IgG2 antibody response, a significantly decreased and shortened viral excretion in nasal swabs and an improved protection to the viral challenge. In contrast, the co-administration of porcine IL-2 or IFN-gamma had no adjuvant effects. Our results thus demonstrate for the first time that the application of porcine GM-CSF gene in a DNA vaccine formulation can exert immuno-adjuvant and protective effects with single vaccination in the natural host pig against Aujeszky's disease.

Adjuvants, Immunologic↗
PubMed1999

The EVH2 domain of the vasodilator-stimulated phosphoprotein mediates tetramerization, F-actin binding, and actin bundle formation.

Vasodilator-stimulated phosphoprotein (VASP) is a member of the Ena/VASP family of proteins that are implicated in regulation of the actin cytoskeleton. All family members share a tripartite structural organization, comprising an N-terminal Ena/VASP homology (EVH) 1 domain, a more divergent proline-rich central part, and a common C-terminal EVH2 region of about 160-190 amino acids. Using chemical cross-linking, sucrose gradient sedimentation, and gel filtration analyses of different truncated VASP constructs, we demonstrate that the VASP EVH2 region is both necessary and sufficient for tetramerization. Moreover, co-sedimentation and fluorescent phalloidin staining showed that the EVH2 region binds and bundles F-actin in vitro and localizes to stress fibers in transfected cells. Analysis of the functional contribution of highly conserved blocks within this region indicated that residues 259-276 of human VASP are essential for the interaction with F-actin, whereas residues 343-380 are required for tetramerization, probably via coiled-coil formation. Interactions with F-actin are enhanced by VASP tetramerization. The results demonstrate that the C-terminal EVH2 segment is not only conserved in sequence but also forms a distinct functional entity. The data suggest that the EVH2 segment represents a novel oligomerization and F-actin binding domain.

Actins↗
PubMed1999

Interactions of heterologous DNA with polyomavirus major structural protein, VP1.

'Empty' polyomavirus pseudocapsids, self-assembled from the major structural protein VP1, bind DNA non-specifically and can deliver it into the nuclei of mammalian cells for expression [Forstová et al. (1995) Hum. Gene Ther. 6, 297-3061. Formation of suitable VP1-DNA complexes appears to be the limiting step in this route of gene delivery. Here, the character of VP1-DNA interactions has been studied in detail. Electron microscopy revealed that VP1 pseudocapsids can create in vitro at least two types of interactions with double-stranded DNA: (i) highly stable complexes, requiring free DNA ends, where the DNA is partially encapsidated; and, (ii) weaker interactions of pseudocapsids with internal parts of the DNA chain.

Animals↗
PubMed1999

Absence of mutations in the YMDD motif/B region of the hepatitis B virus polymerase in famciclovir therapy failure.

BACKGROUND/AIMS: Nucleoside analogues such as lamivudine and famciclovir are potent drugs for treatment of chronic hepatitis B virus infection. Breakthrough infections during lamivudine therapy are associated with mutations in the YMDD motif and putative B region of the HBV polymerase. This study investigated whether failure of famciclovir therapy is also associated with presence or emergence of particular mutations in the HBV polymerase. METHODS: We analyzed longitudinally the sequence of the priming and polymerase domain in seven patients with primary non-response to therapy and two patients with a breakthrough during therapy. Two patients who responded to therapy served as a control. RESULTS: The YMDD motif and the B region were conserved in all isolates. V-->I changes at position 555 just downstream of the YMDD motif were observed before and during therapy in a virus subpopulation of two patients with a primary non-response. In patients with a breakthrough, 378-V-->I and 424-N-->D mutations emerged in the N terminal part of the polymerase domain during follow-up. Lamivudine rescue therapy initiated in four patients, including a patient infected with YMDD(555-V-->I) variants, efficiently reduced viremia. CONCLUSIONS: These data indicate that failure of famciclovir therapy can occur independently of mutations in the YMDD motif or B region of the HBV polymerase and provide a rationale for rescue therapy with lamivudine.

2-Aminopurine↗
PubMed1999

Crosslinking of imprinted proteases to maintain a tailor-made substrate selectivity in aqueous solutions.

A covalent method to keep imprinted properties of proteins stable in aqueous as well as in organic environment is described. To stabilize the ligand induced acceptance for D-configured substrates by alpha-chymotrypsin or subtilisin Carlsberg, each protein was first vinylated by acylation with itaconic anhydride. Then, the tailoring of the derivatized proteins by precipitation in the presence of N-acetyl-D-tryptophan from an aqueous medium with 1-propanol, and the subsequent crosslinking of the enzyme preparations with ethylene glycol dimethacrylate in cyclohexane was carried out. The crosslinked imprinted proteins (CLIPs) obtained catalyzed the hydrolysis of N-acetyl-D-tryptophan ethyl ester in phosphate buffer and the corresponding back reaction in cyclohexane, respectively. The repeated use of CLIP-alpha-chymotrypsin in D-ester hydrolysis was demonstrated. Furthermore, this particular CLIP-alpha-chymotrypsin showed no loss in activity when it subsequently was used in the synthesis of N-acetyl-D-tryptophan ethyl ester in cyclohexane again. In the case of D-ester hydrolysis the reaction rate acceleration (k(enz)/k(nonenz)) was in the same order of magnitude of about 10(4)-10(5) mM(-1) for the two CLIP-proteases. The results suggest that enzymes tailored by imprinting technique do not lose their induced "new" property in the presence of water when they are prepared according to the described vinylation/crosslinking method (CLIP technique).

Chymotrypsin↗
PubMed1999

Transmission of malaria tertiana by multi-organ donation.

In this report, transmission of malaria via a liver, a kidney, and possibly a heart allograft from a single donor is described. The donor had immigrated from Cameroon to Germany 18 months before, but had no clinical signs of active malaria infection. The liver transplant recipient and one of the two kidney transplant patients developed febrile illness with the appearance of Plasmodium vivax in blood smears 5 and 6 wk after transplantation, respectively. In the heart transplant recipient, a subclinical malaria infection was suspected based on a rise of malaria antibodies late after transplantation, whereas the recipient of the second kidney allograft had no clinical or laboratory evidence of malaria. Both liver and kidney recipients with active malaria responded to medical treatment. However, the liver transplant patient developed progressive cholestasis and died 5 months after transplantation from liver failure possibly due to side effects of the malaria medication. Other cases of malaria in solid organ recipients are briefly reviewed.

Adult↗
PubMed1999

Liver transplantation for acute liver failure.

Under conservative management, the mortality rate of acute liver failure is very high. Liver transplantation is an established life-saving therapy, offering survival rates between 60 and 90%. The decision for liver transplantation should be based on prognostic criteria, including patient's age, aetiology of liver disease, degree and onset of encephalopathy, serum bilirubin, prothrombin time or international normalized ratio (INR), serum creatinine, factor V level and arterial pH. Auxiliary liver transplantation is becoming an attractive treatment modality, allowing temporary bridging of liver function until recovery of the native liver. For children with acute liver failure, living related transplantation represents an additional option. In adult patients, living donation is not yet established since the maximum extent of liver resection safely tolerated and the amount of liver tissue necessary for sufficient graft function is still a matter of debate.

Adolescent↗