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Analyses de livres

     

Phage-displayed recombinant single-chain antibody fragments with high affinity for cholesteryl ester transfer protein (CETP): cDNA cloning, characterization and CETP quantification.

Cholesteryl ester transfer protein (CETP) greatly affects the metabolism of all lipoprotein classes including low-density lipoprotein (LDL) and high-density lipoprotein (HDL), both known to constitute powerful risk factors for coronary artery disease (CAD). We now report the successful first cloning and characterization of single-chain antibody fragments specific for CETP. A recombinant phage display library was generated using spleen mRNA isolated from BALB/c mice that had been immunized with highly purified CETP. Screening of the library yielded two single-chain antibody fragments with high affinity for CETP, termed 1CL8 and 1CL10, displaying respective KD values of 4.36 x 10(-9) M and 4.64 x 10(-9) M as determined by affinity sensor technology. Amino acid sequence comparison indicated the complementarity-determining regions of the respective heavy chains to be responsible for CETP high affinity binding. Fragment 1CL8 was successfully employed in clinical chemical quantification systems that uncovered an association in humans between plasma CETP concentration and total body fat mass (r=0.50, p<0.002). Because of the demonstrated superb CETP capturing capacity, combined with high binding affinity to CETP, ready access and unlimited supply, 1CL8 and 1CL10 are expected to prove powerful tools for studies on the role of CETP in atherogenesis.     

Fusion of bone marrow-derived stem cells with cardiomyocytes in a heterologous in vitro model.

OBJECTIVE: Recent studies have demonstrated that transplanted bone marrow-derived stem cells (BMCs) possess a broad differentiation potential and are able to form new cardiomyocytes. However, the identity of BMCs as true cardiomyocytes is still ambiguous. Therefore, we investigated the fate of transplanted fluorescence labeled BMCs and cardiomyocytes in co-culture. METHODS: For cell tracking we used two different fluorescent probes, Vybrant/DiO and Vybrant/DiI. BMCs were taken from human sternal marrow, purified using a Ficoll-gradient-centrifugation, treated with 5-azacytidine and stained with Vybrant/DiO. Furthermore, isolated spontaneous beating cardiomyocytes of neonatal rats (CM) were labeled with Vybrant/DiI. Thereafter, the BMCs were transplanted into CM-cultures and investigated on day 1, 4, 7, 14 and 28 using two-color fluorescence phenotyping by laser-scanning-cytometry (LSC). Two-color positive cells were harvested by patch-clamp technique and beta-MHC mRNA expression was analyzed by single-cell PCR. RESULTS: Two different morphological phenotypes were observed by LSC. First, isolated DiO labeled BMCs without contact or with direct cell contact to DiI labeled CMs. Second, some BMCs and CMs were double positive for DiO/DiI spontaneously forming hybrids. This population increased by 18% from day 1 to 4 and decreased only slightly until day 28. Additionally, few two-color positive cell formations expressed both human and rat specific beta-MHC mRNA as well as only human beta-MHC mRNA indicating that cell-fusion and transdifferentiation has occurred. CONCLUSION: These observations provide in vitro evidence for spontaneous cell fusion and transdifferentiation of BMCs in co-culture, raising the possibility that the observed phenomenons may contribute to development or maintenance of these cell types.     

Meta-analysis of randomized controlled comparisons of psychopharmacological and psychological treatments for anxiety disorders.

BACKGROUND: A number of meta-analyses have led to contradictory results regarding the efficacy of the psychological and pharmacological treatment of anxiety disorders. The main reasons for these inconsistent results seem to be the inclusion of heterogeneous studies and influences of selection biases. We performed a meta-analysis, which only included studies using a direct comparison of pharmacological, psychological, or combined treatments. METHOD: Sixteen studies on panic disorder, six studies on social anxiety disorder, and two studies on generalized anxiety disorder have been analyzed. Effect sizes for differences between the different treatment modalities were calculated. Also, the effect sizes of the pre-post differences were calculated. RESULTS: Pharmacological treatment, cognitive-behavioural treatment, and the combination of both treatment modalities all led to substantial improvement between pre- and post-treatment. Combined pharmacological and psychological treatment was superior to the monotherapies for panic disorder. For social anxiety disorder, there is only preliminary support for combined treatment. Due to lack of sufficient data, no final conclusions can be drawn for generalized anxiety disorder. CONCLUSIONS: While drug treatment and CBT showed equal efficacy, only in panic disorder the combination of pharmacological and psychological treatment was superior to either treatment alone. For the other anxiety disorders, the evidence for greater efficacy of combination treatment is still not sufficient due to lack of studies.     

Arthroscopic treatment of synovial chondromatosis of the ankle

A 34-year-old male soccer player with chronic right ankle dysfunction and a history of repeated ankle joint injuries is presented. Imaging studies revealed synovial chondromatosis of the ankle joint. Arthroscopic partial synovectomy was performed and more than 20 loose bodies were excised. Four months postoperatively the patient was asymptomatic and has returned to his previous level of sport activities. At the latest follow-up, 2 years after the initial diagnosis there is no local recurrence of the disease. Arthroscopy is a minimal invasive surgical technique, with satisfactory results in the treatment of synovial chondromatosis of the ankle joint.     

Posttraumatisches septisches Abdomen

Abdominal infection has the fifth highest incidence of all posttraumatic infections but has the second highest mortality rate with 25%,pneumonia,with 29%, being the only posttraumatic infection that is more frequently lethal.Posttraumatic abdominal sepsis, on the other hand, has a mortality rate of almost 50%.This rate cannot be reduced except by prompt identification of the correct diagnosis of the underlying injury or complication.This means that delayed laparotomy is strikingly detrimental in these patients, with 46% mortality as opposed to 11% in patients who undergo laparotomy promptly. In parallel with this, the mortality of fresh-onset and localized peritonitis is 14%,whereas that of diffuse purulent peritonitis is up to a devastating 42%.     

Rekonstruktion und Stabilisierung nach fehlverheilten Frakturen und Pseudarthrosen im Femurbereich mit Marknagel und anderen Osteosyntheseverfahren (LISS-System)

Malunion and nonunion after fracture present many difficulties in trauma surgery. Selection of the best therapy and operative techique requires careful analysis of the complications. Hyperthrophic nonunion of the femur shaft is mostly best treated with locking reamed nails. Significant differences in torsions after nailing can be corrected by repositioning of the distal interlocking screws if recognized sufficiently early. After fracture healing an open rotation osteotomy is necessary; stabilization can be achieved by means of medullary nails or a condylar plate. How a malalignment of the bone axis is corrected depends on the position of a malunion, the functional deficit caused, and the biomechanical demands on the joint. Condylar plates can often solve the problems in this region. There are also guidelines for ¶the treatment of atrophic and infected nonunions (recommended procedures are ¶aggressive debridement, autologous cancellous bone graft, and biological osteosynthesis), but the treatment of individual cases requires a exhaustive knowledge of and experience in this special field. It is quite common for even well-established procedures to fail. When the bone is biologically reduced and this is the reason for malunion newly developed techniques of internal fixation can be applied. The less invasive stabilization system (LISS), combined with autologous cancellous bone grafting if necessary, can result in healing even in a worst-case scenario.     

Video-enhanced visualization of the larynx and intubation with the Bullard laryngoscope — equipment report

PURPOSE: A simple technical solution is presented to provide video transmission from the tip of a Bullard laryngoscope to a bedside video display, while the operator is still able to look through the viewing ocular of the Bullard laryngoscope during tracheal intubation. EQUIPMENT: This is achieved by insertion of an ultrathin fibreoptic video-endoscopic system into the working channel of the Bullard laryngoscope. Thereby the view from the distal blade tip is transmitted to a bedside monitor, without interfering with the use of the Bullards laryngoscope's original eyepiece. The presented technical solution allows video transmission without considerable additional weight normally associated with attaching video endoscopy cameras, light and camera cables to endoscopic devices. Thus, the Bullard laryngoscope remains lightweight and easy to maneuver. A screw-threaded adapter with a side-port is proposed to prevent displacement of the fibreoptic cable while still allowing application of oxygen. CONCLUSION: Experience and skills with tracheal intubation using the presented video-enhanced Bullard laryngoscope can be achieved in the originally intended way, while the supervisor or attending viewers can follow the tracheal intubation procedure on the video display.     

Tissue engineering of bone for mandibular augmentation in immunocompetent minipigs: preliminary study.

Large mandibular defects caused by trauma, infection or resection of a tumour are still a major problem for plastic and maxillofacial surgeons. The modern concept of tissue engineering combines the osteoinductive effects of osteogenic cells with a suitable scaffold structure to promote differentiation of osteoblasts and optimal matrix production. Critical size mandibular bone defects were therefore made to investigate the osteogenic potential of periosteal cells and a bioabsorbable polymer fleece (Ethisorb 510) in minipigs. Periosteal cells were isolated from four minipigs, expanded in vitro and seeded with fibrin glue into Ethisorb 510 fleeces. Tissue constructs were used to repair critical size mandibular defects and compared with two minipigs with untreated bone defects. Bone healing was evaluated after 90 and 180 days by radiographs and a histological scoring system. The radiographs showed increased radiodensity of defects filled with the cell-fibrin-fleece-constructs compared with the untreated control group after 90 and 180 days in vivo. The defects repaired by the cell-fibrin-scaffolds (180 days in vivo) obtained the highest histological mean score 2.9 (range 2-3), while defects filled by cell-fibrin-scaffolds (90 days in vivo) achieved a mean score of 2.1 (range 2-3). In contrast, the control group (n = 2) scored 1 and 2. The results show that a combination of periosteal cells and polymer fleeces may be a promising approach for clinical mandibular augmentation.