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Biomedical subjects

C König

Publications and source records attributed to C König.

At least 19 recordsLinked to original sources
PubMed2001

Factors compromising antibiotic activity against biofilms of Staphylococcus epidermidis.

Several factors associated with bacterial biofilms were studied for their role in phenotypic resistance to antibiotics. These factors included bacterial slime extracted from biofilms, reduced growth rates of biofilm-embedded bacteria and high bacterial inocula. Antibiotic activity against suspended bacteria in the presence of these factors, either alone or combined, was compared with activity against adherent biofilms. All MICs, determined by standard susceptibility tests, were below the sensitivity breakpoints for Staphylococcus epidermidis strain V2. The addition of bacterial slime to suspended bacteria reduced the bactericidal activity of glycopeptides but had less or no effect on the activity of the other antibiotics tested. High bacterial inocula affected the activity of flucloxacillin and quinolones only moderately or not at all, though a more pronounced effect on glycopeptides was observed. In contrast, the bactericidal activity of most antibiotics was severely compromised when adherent bacterial biofilms were used as inocula. In conclusion, the presence of slime, slow growth rates and high bacterial counts may explain the poor activity of glycopeptides against biofilm-embedded organisms, but these factors, either alone or in combination, do not explain the lack of bactericidal activity of other drugs against biofilms. Thus, additional factors need to be identified.

Anti-Bacterial Agents↗
PubMed2001

[Technique and results of CT-guided percutaneous bone biopsy].

PURPOSE: The aim of the study was to evaluate the feasibility and results of CT-guided percutaneous bone biopsy (PBB) of unknown bone lesions in a representative number of patients. METHODS: In 92 patients (100 biopsies) with different bone lesions CT-guided PBB was performed. RESULTS: The rate of technical success, defined as a successful retrieval of a sufficient tissue sample which then was sent for histological evaluation, was 89% (89/100 biopsies). The diagnostic accuracy was defined as a clinically useful histological result and was obtained in 80% (80/100 biopsies). Minor complications (minimal bleedings) occurred in 3% of all biopsies, no special therapy was necessary. Osteolytic lesions (92%) were classified more accurately by PBB than osteoplastic (80%) or mixed lesions (67%). Considering the anticipated dignity of the lesions prior to PBB, the suspected malignant bone lesions had a better diagnostic accuracy of 82% than the suspected benign bone lesions with an accuracy of 50%. CONCLUSION: Due to its universal availability combined with a low risk and a high diagnostic value the PBB of unknown bone lesions can be regarded as a valuable diagnostic tool. However, leave-me-alone lesions should be excluded.

Biopsy, Needle↗
PubMed2001

Platelet alloantibodies in transfused patients.

BACKGROUND: Patients receiving cellular blood components may form HLA antibodies and platelet-specific alloantibodies. STUDY DESIGN AND METHODS: Serum samples from a cohort of 252 patients with hematologic or oncologic diseases who are receiving cellular blood components were studied for platelet-reactive antibodies. Specificity of platelet alloantibodies was determined with a panel of typed platelets RESULTS: Platelet-reactive antibodies were detected in the sera of 113 patients (44.8% of 252), HLA antibodies in the sera of 108 (42.9%), and platelet-specific antibodies in the sera of 20 (8%). The following platelet-specific antibodies were identified: anti-HPA-5b (n = 10), anti-HPA-1b (n = 4), anti-HPA-5a (n = 2), anti-HPA-1a (n = 1), anti-HPA-2b (n = 1), anti-HPA-1b+5b (n = 1), and anti-HPA-1b+2b (n = 1). Fifteen sera from the 108 patients with anti-HLA (13.9%) contained additional platelet-specific alloantibodies, while in 5 sera, platelet-specific alloantibodies only were detected: anti-HPA-5b (n = 4) and anti-HPA-1a (n = 1). Of the 108 sera with HLA antibodies, 29 (26.9%) showed discordant results when studied with the lymphocytotoxicity test and the glycoprotein-specific immunoassay. Ten sera contained panreactive antibodies against platelet glycoproteins (GP) IIb/IIIa, GPIa/IIa, and/or GPIb/IX. Alloimmunization occurred in 58.3 percent of female patients with previous pregnancies, but in only 23.3 percent of those without previous pregnancies (p = 0.0049). CONCLUSION: Platelet alloantibody specificities in transfused patients (predominantly anti-HPA-5b and -1b with antigen frequencies <30% among whites) differ significantly from those observed in patients with neonatal alloimmune thrombocytopenia or posttransfusion purpura, in whom anti-HPA-1a (antigen frequency >95%) is the most prevalent specificity. HLA antibody detection yields discordant results when the lymphocytotoxicity assay and a glycoprotein-specific immunoglobulin-binding assay are used.

Antigens, Human Platelet↗
PubMed2001

New strategies in platelet inhibition in noncoronary interventions.

Thrombembolic complications frequently occur during and after endovascular procedures because of associated arterial injury and thrombotic characteristics of implanted devices such as stents. New strategies in platelet aggregation inhibition are now available blocking the final and common pathway of platelet aggregation, the glycoprotein IIb/IIIa receptor. This treatment modality seems to be more effective for prophylaxis and prevention of thrombembolic complications than standard antiplatelet therapy. Most of the data provided for glycoprotein IIb/IIIa receptor blockade are derived from studies of coronary interventions. This report reviews the pharmacodynamic differences of classic and new drugs for platelet inhibition and the basic considerations for antiplatelet therapy in noncoronary interventions.

Arteries↗
PubMed2001

[MR-venography using manual flow augmentation in an open low field MR system].

OBJECTIVE: To evaluate the feasibility of signal enhancement in the deep veins by means of manual compression of the calf (flow augmentation) as a new approach to MR venography in open configuration, low-field systems. METHODS: 10 healthy volunteers underwent MR venography of the calf unconstrained and during short localized manual compression. Gradient recalled echo sequences (FLASH, FISP) with repeated single slice acquisition and first-order gradient motion refocussing were tested in four protocols with and without arterial presaturation slabs (scan time 2.2 - 5.0 s per slice). The effect on flow enhancement was rated by means of a signal score. Interventional accessories, particularly an in-room LCD screen, were required for interactive application of compression manoeuvres. RESULTS: Sequences with arterial presaturation slabs were superior to those without regardless of the longer acquisition times. Careful targeting of compression to the mid-time of data acquisition was crucial to obtain marked flow acceleration. Enhancement was best in the case of proximally applied calf compression. Signal improvement was consistently achieved in the proximal parts of the posterior tibial and peroneal veins, but was only seen in 4/10 volunteers in the distal part of the anterior tibial vein. CONCLUSION: Flow augmentation by means of manual calf compression is a simple and effective complementary approach to MR venography in open configuration, low field MR systems.

Adult↗
PubMed2001

Linear IgA bullous dermatosis induced by atorvastatin.

Linear IgA bullous dermatosis (LABD) is an autoimmune blistering skin disease characterized by circulating IgA antibodies binding the basement membrane zone. In most cases the origin is not clear, but in a minority of cases LABD is drug induced. We describe a patient in whom linear IgA disease developed shortly after beginning therapy with atorvastatin. In Western blotting analysis we detected IgA and IgG class antibodies targeting a 97-kd protein. To our knowledge this is the first reported case of atorvastatin-induced LABD.

Anticholesteremic Agents↗
PubMed2001

Bullous pemphigoid in a patient treated with UVA-1 phototherapy for disseminated morphea.

Bullous pemphigoid is an autoimmune disease of the skin characterized by the production of antibodies directed at structures of the basement membrane zone (BMZ) leading to subepidermal blisters. Several causative triggers have been described in the literature, among them UV light. Here, we report on a 73-year-old Caucasian female with disseminated morphea who developed blisters on her extremities after receiving whole-body UVA-1 phototherapy. The initial differential diagnosis of a phototoxic versus photoallergic reaction was ruled out as the lesions continued to spread after discontinuation of phototherapy. Histological and direct immunofluorescence examination showing a subepidermal blister and linear IgG deposits along the BMZ along with detection of circulating anti-BMZ antibodies led to the diagnosis of bullous pemphigoid. Immunosuppressive therapy resulted in regression of all blisters. After ruling out other possible causes, such as neoplasias or drugs, we conclude that UVA-1 has to be regarded as the most likely trigger of the disease.

Aged↗
PubMed2001

A new device for percutaneous suture-mediated closure of arterial puncture sites using exteriorized needles: initial experience.

PURPOSE: To assess the feasibility and initial clinical results of Closer (Perclose, Redwood City, California), a new device for percutaneous suture-mediated closure of arterial puncture sites. METHODS: Vascular interventions were performed using 6 and 7 French sheaths in 22 consecutive patients. All patients underwent suture-mediated percutaneous closure with the new device. Patients were followed by physical examination the day after the procedure. RESULTS: Immediate hemostasis was achieved in 20/22 patients (91%). In 3 out of 5 antegrade closures, only one suture was captured. In two cases, this was managed by reinsertion of a second device. In another patient, hemostasis was not achieved by the device due to knot entrapment. No major complications were observed. The overall rate of minor complications was 9% (2/22) due to hematomas without the need for blood transfusions. CONCLUSION: Percutaneous suture with this new device is an acceptably safe and effective method to achieve immediate hemostasis of the arterial access site after interventional procedures with minimized manipulation of the puncture track.

Adult↗
PubMed2000

[MRI-guided percutaneous radiofrequency ablation of hepatic neoplasms--first technical and clinical experiences].

PURPOSE: To evaluate the safety and efficacy of MR-guided radiofrequency ablation (RFA) of hepatic neoplasms. MATERIAL AND METHODS: 16 hepatic neoplasms (1.3-3.0 cm in diameter) in 11 patients were treated by 22 percutaneous RFA sessions during a prospective study. 16 G, MR-compatible cooled-tip electrodes with active lengths of 2 cm and 3 cm, respectively, were placed under MR-guidance in an open 0.2 Tesla MR system (Magnetom Open, Siemens, Erlangen) using fast T1-weighted sequences. Pretreatment studies, evaluation of tumor necrosis (one week after last RFA), and further follow-up studies every 3 months were performed using 1.5 Tesla MR systems. RESULTS: The mean procedure time was 2.8 (1.5-3.3) h. Complications related to percutaneous treatment were not encountered. 14 of 16 neoplasms (87%) showed no CM enhancement during MRI after the last RFA and were judged to be completely necrotic. In 11 tumors one treatment session was necessary, in 4 tumors two and in one tumor three. Follow-up studies revealed persistent complete necrosis in 13 of 14 (93%) tumors during a period of 3-18 (median: 11.8) months. In 5 patients new intrahepatic tumors developed that were not suitable for further RFA treatment because of their number, size and location. CONCLUSION: MR-guided RFA using single cooled tip electrodes is safe and technically effective for treatment of hepatic neoplasms up to 3 cm in size, however further improvements are necessary.

Adult↗
PubMed2000

[Pulsed spray lysis with reteplase in peripheral arterial occlusions--technique and initial results].

PURPOSE: Urokinase followed by rt-PA are the most frequently used drugs approved for thrombolysis in peripheral arteries in the USA and Europe. We wanted to test the safety and efficacy of low-dose reteplase administered by pulsed spray technique. MATERIALS AND METHODS: 10 patients with acute or subacute occlusion of a peripheral artery (n = 8) or graft (n = 2) were treated (history 8 +/- 17 days; occlusion length 4-60 cm, mean 23 cm). Reteplase was administered as an intra-arterial (i.a.) bolus (0.5 U/10 cm of occlusion length) followed by pulsed spray lysis (1 U/h for the first 2 h, then 0.5 U/h). The catheter was placed into the occlusion. In addition the patients received heparin (i.a.) and aspirin (oral). The site of puncture was closed with a percutaneous suturing system prior to discontinuation of heparin treatment. RESULTS: A total dose of 3.3 +/- 1.2 U reteplase was administered. The primary success rate was 7/10. Two distal embolizations and two bleeding complications were observed (one minor bleeding at the site of puncture and one rupture of the suture which had to be treated surgically). CONCLUSION: With regard to our limited data, low-dose i.a. reteplase seems to be safe and effective. Two bleeding complications were observed which both occurred at the site of puncture. Discontinuation of heparin treatment prior to sheath removal is recommended. Fibrinolysis with reteplase may be an alternative to urokinase or rt-PA.

Aged↗
PubMed1999

Inactivation of the p53-homologue p73 by the mdm2-oncoprotein.

The p73beta protein shares structural and functional similarities with the tumor suppressor gene product p53. Both proteins activate transcription from p53-responsive promoters. p53's activity is antagonized by the mdm2 protein (also termed hdm2 in human cells). Complex formation between p53 and mdm2 results in p53's transcriptional inactivation and destabilization. Here we show that overexpression of mdm2 reduces p73beta's ability to activate transcription, too. The mdm2 protein forms a specific complex with p73beta in vitro with an efficiency comparable to p53-binding. Further, both p73beta and p53 relocalize a transport-defective mutant of mdm2 from the cytoplasm to the nucleus, arguing that complex formation occurs in vivo as well. Mutational analysis suggests that the interaction between p73beta and mdm2 follows structural principles analogous to the p53-mdm2-complex. Whereas p53 is destabilized in the presence of mdm2, the amount of intracellular p73beta was not detectably reduced by mdm2. The carboxyterminal RING finger domain of mdm2 was found to be required to reduce the intracellular abundance of p53, but it was dispensable for transcriptionally inactivating either p53 or p73beta. Our results suggest that the autoregulatory feedback loop between p53 and mdm2 also controls p73's activity, but that mdm2-mediated protein degradation is unique to p53.

Biological Transport↗
PubMed1999

A recessive mutation leading to vertebral ankylosis in zebrafish is associated with amino acid alterations in the homologue of the human membrane-associated guanylate kinase DLG3.

We describe the characterization of the zebrafish homologue of the human gene DLG3. The zebrafish dlg3 gene encodes a membrane-associated guanylate kinase containing a single PDZ domain. This gene was cloned using a gene-trap construct inserted in the gene's first intron. The insertion co-segregates with a viable mutation called humpback (hmp), which leads to formation of ankylotic vertebrae in adult fishes. Insertion and mutation have both been mapped to chromosome 12, in a segment which is syntenic with region p12 to q12 of human chromosome 17. The hmp mutant phenotype, however, appears to be due to two point mutations in the guanylate kinase domain rather than to the transgene insertion itself. The results of this study are discussed in the light of the possible function of the guanylate kinase domain.

Animals↗
PubMed1999

The frequency of phospholipase A2 binding of basophilic granulocytes does not decrease during bee-venom-specific immunotherapy.

BACKGROUND: The major allergenic component of bee venom is phospholipase A2 (PLA2). METHODS: In this study, PLA2 was used to analyze and enrich PLA2-binding cells from peripheral blood by high gradient magnetic cell sorting. RESULTS: In normal donors, the frequency of allergen (PLA2)-binding cells among peripheral blood mononuclear cells (PBMC) as determined by flow cytometry is below 0.1%, whereas in bee-venom-allergic patients, PLA2-binding cells are readily detectable at frequencies of up to 2.3%. In severely bee-venom-allergic patients, many basophilic granulocytes are present, as defined by anti-CD9, CD25, and CD38 mAb, comprising up to 95% of the PLA2-binding cells. From blood of allergic and normal donors, about equal absolute numbers of allergen-binding CD19/21-positive B cells can be enriched. Severe anaphylactic reactions (Mueller grade IV) and failure of or adverse reactions during immunotherapy are associated with high numbers of circulating allergen-binding basophils. Interestingly, in the patients studied, the number of PLA2-binding basophilic granulocytes did not markedly change during rush immunotherapy and up to 6 months of maintenance immunotherapy. CONCLUSIONS: The specific and reproducible enrichment of PLA2-binding cells provides a new tool for the analysis and monitoring of effector cells in bee-venom-allergic patients with immediate-type hypersensitivity.

Adolescent↗
PubMed1999

Adenovirus type 5 E4orf3 protein relieves p53 inhibition by E1B-55-kilodalton protein.

The E1B-55-kDa protein of adenovirus type 5 and the p53 tumor suppressor gene product form a complex that localizes to the cytoplasm, thereby downregulating p53's transcriptional activity. The E4orf6 protein binds and relocalizes E1B-55-kDa, and the proteins act synergistically to inactivate p53. We show that another adenovirus E4 gene product, E4orf3, is also sufficient to relocalize E1B-55-kDa from the cytoplasm to the nucleus. Both proteins are then found in discrete nuclear structures (tracks) that are known to contain components of the promyelocytic leukemia-associated nuclear structure. Simultaneously, p53 is dissociated from E1B-55-kDa and is found evenly distributed over the nucleoplasm. In the presence of E4orf3, p53-dependent transcriptional activity is no longer repressed by E1B-55-kDa. When E1B-55-kDa is coexpressed with E4orf3 and E4orf6, E1B-55-kDa is found to colocalize with E4orf6 rather than E4orf3. In parallel, p53 is inhibited and degraded by the combination of E1B-55-kDa and E4orf6, regardless of coexpressed E4orf3. This suggests that the effects of E4orf6 on E1B-55-kDa overrule the actions of E4orf3. When cells are infected with virus expressing E4orf3 but not E4orf6, E1B is found in the cell nucleus and p53 enters the virus replication centers. After infection with wild-type adenovirus, E4orf3 is expressed before E4orf6 and E1B temporarily colocalizes with E4orf3 in nuclear tracks before associating with E4orf6. We propose that during adenovirus infection, the E4orf3 protein transiently liberates p53 from its association with E1B-55-kDa. Subsequently, p53 is inactivated and degraded by the combination of E1B-55-kDa and E4orf6.

Adenovirus E1B Proteins↗
PubMed1998

Bacterial concentrations in pus and infected peritoneal fluid--implications for bactericidal activity of antibiotics.

Little is known about how many bacteria are present at an infectious focus at the onset of antibiotic therapy. The number of cfu was determined in pus and infected peritoneal fluids obtained from 41 patients. Pathogens were detected in 71% of specimens. There were high concentrations of bacteria in culture-positive samples, in both soft-tissue and peritoneal infections, averaging 2 x 10(8) cfu/mL. These concentrations were much higher than the standard inoculum size used in in-vitro susceptibility tests, 5 x 10(5) cfu/mL. The impact of this discrepancy on antibacterial efficacy was studied with amikacin, ciprofloxacin, imipenem and piperacillin against Escherichia coli and Staphylococcus aureus. The inhibitory and bactericidal activities of amikacin and ciprofloxacin determined with high inocula were two to four times lower than with standard inocula, whereas the activity of piperacillin was diminished at least 128-fold. Similar activity was observed with these drugs in Mueller-Hinton broth and peritoneal fluid. The bactericidal activity of imipenem was reduced in peritoneal fluid. Thus, conditions prevailing at the infection site may compromise antibiotic activity determined in vitro.

Abdominal Abscess↗
PubMed1998

Inactivation of p53 but not p73 by adenovirus type 5 E1B 55-kilodalton and E4 34-kilodalton oncoproteins.

The adenovirus E1B 55-kDa and E4 34-kDa oncoproteins bind and inactivate the p53 tumor suppressor gene product, resulting in cell transformation. A recently discovered cellular protein, p73, shows extensive similarities to p53 in structure and function. Here we show that the simultaneous transient expression of E1B 55-kDa and E4 34-kDa proteins is sufficient to drastically shorten the intracellular half-life of p53, leading to strongly reduced steady-state p53 levels. Concomitantly, the E1B 55-kDa and E4 34-kDa proteins act synergistically to inactivate the transcriptional activity of p53. Mutational analysis suggests that physical interactions between the E1B 55-kDa protein and p53 and between the E1B 55-kDa and E4 34-kDa proteins are both required for p53 degradation. In contrast, the ability of p53 to interact with the cellular mdm2 oncoprotein or with its cognate DNA element appears to be dispensable for its destabilization by adenovirus gene products. The adenovirus E1B 55-kDa protein did not detectably interact with p73 and failed to inhibit p73-mediated transcription; also, the E1B 55-kDa and E4 34-kDa proteins did not promote p73 degradation. When five amino acids near the amino termini were exchanged at corresponding positions between p53 and p73, this rendered p53 resistant and p73 susceptible to complex formation and inactivation by the E1B 55-kDa protein. Our results suggest that while p53 inactivation is a central step in virus-induced tumor development, efficient transformation can occur without targeting p73.

Adenovirus E1B Proteins↗
PubMed1997

Autosterilization of biodegradable implants by injection molding process.

Sterilization of degradable implants by standard procedures may damage the parts due to the labile chemical nature of the polymers. This study examined whether the injection molding process used for the production of polymeric parts may itself sterilize the implant due to high temperature, pressure, and shear forces applied. Poly-D,L-lactic acid (PDLLA) and poly-L-lactic acid (PLLA) granules were contaminated with thermoresistant spores of Bacillus stearothermophilus (>10(5) spores/g). Sterile and contaminated granules of both polymers were injection molded and tested for sterility. All 27 samples produced with sterile PDLLA and processed at 120 degrees C and all 18 samples produced with sterile PLLA at 200 degrees C remained sterile after injection molding and handling. However, in five out of 28 PDLLA samples and in one out of 26 PLLA samples produced with contaminated material, spores had survived the process. In conclusion, the injection molding process could not reliably sterilize parts produced with polylactic acid granules that were heavily contaminated with thermoresistant organisms. However, the number of viable spores was significantly reduced by more than 99.99%. Thus, the injection molding process might allow the autosterilization of parts produced with raw material that is not heavily contaminated.

Biocompatible Materials↗