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Biomedical subjects

C König

Publications and source records attributed to C König.

At least 19 recordsLinked to original sources

Molecular epidemiology of West Nile Virus in humans.

After the introduction of West Nile Virus into the United States of America in 1999 followed by annual WNV epidemics during the mosquito seasons and spreading of the virus from the East (New York; 1999) to the West of the U.S. (California; 2003/2004) there appeared the question of whether a similar scenario could happen in Europe, too. To be able to answer this question the German Ministry of Health decided to investigate the prevalence and incidence of WNV infections in German blood donors. First a test algorithm was established taking into account the high level of cross-reactivity between different flavivirus infections in serological test systems. AntiWNV-suspicious specimens were further investigated for their neutralisation capacity and by an antiWNV confirmation assay developed in-house. As a preliminary result of our studies a very low prevalence of WNV infections in healthy German blood donors was measured. Development of highly specific test systems is necessary for accurate and reliable differential diagnosis of flavivirus infections.

Antibodies, Viral↗

Magnetic resonance imaging guided corticosteroid injection of sacroiliac joints in patients with spondylarthropathy. Are multiple injections more beneficial?

Efficacy of a second magnetic resonance (MR) imaging guided corticosteroid injection of inflamed sacroiliac joints (SIJ) in patients with spondylarthropathy. Thirty-one patients received 50 injections in an outpatient basis. Fifteen of 31 patients who relapsed or were non-responders received a second injection. All had MR guided injection of 40 mg triamcinolone acetonide into SIJ using an open 0.2 Tesla unit. Twenty of 31 patients after the first injection, and 9 of 15 patients after the second injection reported subjective improvement, which lasted for a mean of 8.7+/-10.9 and 16.1+/-15.8 months for each group. Subchondral bone marrow edema resolved in 15 of 20 patients who reported subjective improvement, after the first injection. No complications occurred. MR guided steroid injection of SIJ is effective and safe. Since there is no exposure to radiation it could be performed many times. Repeated injections seem to be beneficial for primary non-responders and patients who relapsed.

Adolescent↗

[Children: improving the prevention and early advancement in children with behavioral- and developmental disorders in the Ennepe-Ruhr District].

Developmental behavioural disorders in early childhood are a serious public health problem, because they signify a higher risk of social, regulatory and emotional impairment in later life. The public health office in Ennepe-Ruhr develops in cooperation with the communities a programme of health promotion for children and their families. An important motive is continually rising costs for supporting children with developmental problems. An element in the programme is a project of counselling mothers with babies and toddlers with excessive crying, serious sleep disorders and anxiety problems. This example of early intervention promises short-term relief, early identification of problem children and the strengthening of parental resources. A key issue is the introduction of a systematic evaluation of all communal funding for measures of support for preschool children. It shows that such measures start relatively late, and the coordination at community level is not always optimal. Some progress has been made, but criteria to measure the efficiency of current health promotion are still lacking. According to public health research early intervention for risk groups (single mothers, migrant families or families depending on public assistance) promises to give children and their families a better social and health perspective in life. It should be a primary health target for communities to develop evidence-based health programmes for children, focussing on mental and social well-being. Studies indicate that such interventions might have positive financial results.

Adolescent↗

Synaptic congenital myasthenic syndrome in three patients due to a novel missense mutation (T441A) of the COLQ gene.

Congenital myasthenic syndromes (CMS) with deficiency of endplate acetylcholinesterase (AChE) are caused by mutations in the synapse specific collagenic tail subunit gene (COLQ) of AChE. We identified a novel missense mutation (T441A) homozygously in three CMS patients from two unrelated German families. The mutation is located in the C-terminal region of the ColQ protein, which initiates assembly of the triple helix, and is essential for insertion of the tail subunit into the basal lamina. Density gradient analysis of AChE extracted from muscle of one of the patients revealed the absence of asymmetric AChE. All patients were characterized by an onset of disease in childhood, exercise-induced proximal weakness, absence of ptosis and ophthalmoparesis, a decremental EMG response, and deterioration in response to anticholinesterase drugs. However, age at onset, disease progression, disease severity, and functional impairment varied considerably among the three patients. As adults, two siblings from one family experience only mild impairment, while the third patient requires a wheelchair for most of the day and assisted ventilation at night.

Acetylcholinesterase↗

[Differential diagnosis of bullous skin lesions in neonates: pemphigoid gestationis].

The clinical relevance of bullous skin diseases in newborns varies widely. We present the case of a preterm, 35 weeks of gestation, infant who was admitted to our hospital with skin lesions on face, thorax and plantae. There were no other pathological findings on clinical and neurological examinations. During another pregnancy the mother of the child had already suffered from pemphigoid gestationis. In the blood of the newborn complement-fixing auto-antibodies against BP180, the common antigen of pemphigoid gestationis and bullous pemphigoid, were detected. The skin lesions disappeared after a few days of local antiseptic therapy. Pemphigoid gestations is a rare autoimmune dermatosis in pregnancy. The frequency of skin lesions in newborns of mothers with pemphigoid gestationis is estimated to about 5 -- 10 %.

Diagnosis, Differential↗

Radiopaque markers in endovascular stents--benefit and potential hazards.

AIM: The primary objective of this study was to evaluate the impact of radiopaque markers on stent visibility. The secondary objective was to investigate the impact of such radiopaque markers on localized corrosion at the stent corpus-marker interfaces. MATERIAL AND METHODS: The radiopacity of the following stents was evaluated at different fluoroscopy modes (spotfilm, continuous fluoroscopy, 15 p/s, 7.5 p/s, 3 p/s): Memotherm Flexx (FX), Memotherm Luminexx (LX)(Bard), SMART (SM), SMARTeR (SMR)(Cordis). Four readers evaluated a total of 3200 images (160 per stent per fluoro mode) according to the following radiopacity score (RS): 0 = no stent visible, 1 = poor, 2 = acceptable, 3 = good, and 4 = very good stent visibility. LX and SMR stents (n = 5/group) were subjected to potentiodynamic polarization testing in de-aerated Hanks salt solution at 37 degrees C using a potentiostat. Palmaz-Schatz stents (n = 3) were used as the control group for comparative evaluation. The corrosion current density (I corr ) and the breakdown value (E bd ) were compared parameters of interest. RESULTS: At the spotfilm mode the LX, the SM and the SMR were rated well to very well visible in 99 %, 96 %, 96 %, and the FX only in 64 %. At 7.5 p/s (standard fluoro mode) the LX was considered to be well to very well visible in 77 %, followed by the SMR in 12.5 %, the SM in 1 %, and the FX in 0 %. The SMR stents exhibited the highest E bd values (802 +/- 112 mV vs SCE), while the LX stents exhibited the lowest E bd values (155 +/- 38 mV vs SCE). Also, the average E bd values for the SMR stents were better than those exhibited by the PS stents (503 +/- 107 mV vs SCE). CONCLUSION: Stent radiopacity can be increased significantly with the help of radiopaque markers (p < 0,0001 LX vs. FX). However, the surface condition of the stent corpus and the mode of attachment of the marker onto the corpus may have a significant impact on the uniformity of the final corrosion behavior. It is not feasible to determine the clinical impact of this localized corrosion behavior from this in vitro study. Further experimentation is recommended to ascertain the same.

Coated Materials, Biocompatible↗

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↗

[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↗

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↗

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↗

[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↗

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↗

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↗

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↗

[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↗

[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↗

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↗