Use of computed tomography sinography for evaluation of draining tracts in 27 dogs and one cat.

OBJECTIVES: To describe the clinical findings, imaging findings and outcome in patients in which CT sinography was performed, and assess to what degree this technique adds information about the extent of a tract or increases the accuracy of diagnosis of foreign bodies on CT. MATERIALS AND METHODS: Retrospective review of medical records of 27 dogs and one cat with draining tracts that had CT sinography. Pre- and post-intravenous (IV) contrast CT series were compared with CT sinography in each patient. RESULTS: Median duration of clinical signs before referral was 85 days (range 2 to 1478 days). The most common reported clinical signs were swelling (14/28, 50%) and regional pain (5/28, 18%). CT sinography revealed a more extensive tract than post-IV contrast CT in 21% cases. On post-IV contrast CT, 31% of foreign bodies were detected compared to 23% on CT sinography. All four foreign bodies detected by CT were observed in the non-contrast images. Surgery was performed after CT in 22 (79%) cases. Thirteen (46%) draining tracts resolved after surgery, three (11%) resolved without surgery, six (21%) persisted or recurred after surgery, and six (21%) were lost to follow-up. CLINICAL SIGNIFICANCE: CT sinography provides limited additional information about the extent of draining tracts compared to pre- and post-IV contrast CT images and did not increase the number of foreign bodies identified.

[Ear aid in Myanmar]. / Ohrenhilfe in Myanmar.

As the example of a small team working in Myanmar since 2010 has demonstrated, it is possible to achieve sustainable success in medical education and training in foreign countries with relatively little effort, in this case in middle ear surgery. The main requirements are outstanding communication within the team as well as with the authorities, organizations, and colleagues on site. Equally important is mindful and respectful work in the hosting country and the consideration of cultural particularities. Essential contributing factors for long-term success are intercultural exchange, interpersonal relationships, and especially the motivation of colleagues on site, which together create a foundation of trust. This trust combined with regular exchange visits enables constant professional development according to the current needs.

Preclinical pharmacokinetics and biodistribution of subcutaneously administered glycoPEGylated recombinant factor VIII (N8-GP) and development of a human pharmacokinetic prediction model.

Essentials N8-GP is an extended half-life recombinant factor VIII (FVIII) for the treatment of hemophilia A. Subcutaneous (SC) FVIII dosing might reduce the treatment burden of prophylaxis. SC N8-GP has a favorable PK profile in animal models and disappears from skin injection sites. Combined animal (SC) and clinical (IV) data suggest that daily SC dosing may provide prophylaxis. SUMMARY: Background N8-GP is an extended half-life recombinant factor VIII (FVIII) for the treatment of hemophilia A. Subcutaneous administration of FVIII may reduce the treatment burden of prophylaxis; however, standard FVIII products have low bioavailability after subcutaneous dosing in animals. Objective To evaluate the pharmacokinetics, effectiveness and local distribution of subcutaneously administered N8-GP in preclinical models and predict the human pharmacokinetic (PK) profile. Methods The pharmacokinetics of subcutaneously administered N8-GP were evaluated in FVIII knockout (F8-KO) mice and cynomolgus monkeys; a human PK prediction model in hemophilia A patients was developed. The hemostatic effect was evaluated in a tail vein bleeding model in F8-KO mice. The injection-site distribution and absorption of subcutaneously administered N8-GP were assessed in F8-KO mice by the use of temporal fluorescence imaging and immunohistochemistry. Results Subcutaneously administered N8-GP had a bioavailability, a first-order absorption rate and a half-life, respectively, of 24%, 0.094 h-1 and 14 h in F8-KO mice, and 26%, 0.33 h-1 and 15 h in cynomolgus monkeys. A dose-dependent effect of subcutaneously administered N8-GP on blood loss was observed in mice. A minimal amount of N8-GP was detected at the injection site 48-72 h after single or multiple dose(s) in F8-KO mice. Subcutaneously administered N8-GP was localized to the skin around the injection site, with time-dependent disappearance from the depot. PK modeling predicted that subcutaneously administered N8-GP at a daily dose of 12.5 IU kg-1 will provide FVIII trough levels of 2.5-10% in 95% of patients with severe hemophilia A. Conclusions Subcutaneously administered N8-GP may provide effective hemophilia A prophylaxis. A phase I clinical trial is underway to investigate this possibility.

Paenibacillus larvae Phage Tripp Genome Has 378-Base-Pair Terminal Repeats.

Paenibacillus larvae bacteriophage Tripp was isolated from an American foulbrood diseased honey bee hive in North Carolina, USA. The 54,439-bp genome is 48.3% G+C, encodes 92 proteins, no tRNAs, and has 378-bp direct terminal repeats. It is currently unique in Genbank.

[Somatosensoric tinnitus]. / Somatosensorischer Tinnitus.

Tinnitus can be caused or triggered by functional disorders of the cervical spine, temporomandibular joint or any other musculoskeletal structure of the neck or head. This special form of tinnitus is called somatosensory tinnitus and represents a discrete subgroup among the different kinds of tinnitus. Distinctive for this kind of tinnitus are alterations in volume and frequency during movement or the stimulation of certain muscles and joints. This can be evaluated using a structured testing method. To be able to easily perceive tinnitus modulations, the test must be performed in total silence. Effective treatment modules are physiotherapy, osteopathy, neural therapy, and Qigong for self-help.

Infants under the age of six months with acute mastoiditis. A descriptive study of 15 years in Sweden.

OBJECTIVE: To investigate the occurrence, clinical signs and outcome of acute mastoiditis in infants under the age of 6 months in Sweden between the years 1993-2007. METHODS: All ENT departments in Sweden reported children 0-5 months treated for acute mastoiditis 1993-2007 and all records were reviewed. The clinical course and various characteristics were recorded. RESULTS: Seventeen young infants with acute mastoiditis were identified. Three patients had suffered acute otitis media earlier, otherwise the children were previously healthy. Preceding the episode of acute mastoiditis, the children had an upper respiratory tract infection or fever for seven days in mean (median three days) and the mean number of days with ear-symptoms was three days (median two days). Three patients were treated with antibiotics prior to admittance. Almost all children presented with clear retroauricular signs with protruding ear and redness behind the ear. The children were hospitalised for six days (mean and median). Eight patients (47%) suffered from a subperiosteal abscess. All but one patient underwent surgery: myringotomy (13); incision or punction of the mastoid (5); mastoidectomy (3). Streptococcus pneumoniae was the most frequent bacterium identified in cultures. No intracranial complications or other severe complications were found. CONCLUSION: Acute mastoiditis is extremely rare in infants under the age of 6 months. The patients in this study did not have any predisposing diseases. An upper respiratory tract infection had preceded the episode of acute mastoiditis for some time in the majority of cases, but the time from first ear symptoms to hospitalization was very short. Acute mastoiditis is a potentially life-threatening disease, but the timely administration of intravenous antibiotics and surgical intervention prevented the occurrence of severe complications in these young infants.

[Disseminated intravascular coagulopathy in a dog with Angiostrongylus vasorum infection]. / Disseminierte intravasale Koagulopathie bei einem Hund mit Angiostrongylus-vasorum-Infektion.

A 2-year-old female spayed Epagneul-Breton dog was presented with ecchymoses, but an undisturbed general condition. Clinical examination additionally revealed petechia and a haematoma. Travel history included Italy and Denmark. Laboratory abnormalities were moderate thrombocytopenia, prolonged PT, aPTT and TT, and elevated d-dimers. Initial therapy consisted of plasma transfusions, fluids, doxycycline and famotidine administration. Babesiosis, ehrlichiosis, leishmaniosis, dirofilariosis or anaplasmosis could not be confirmed. Abdominal ultrasound was unremarkable, while thoracic radiographs showed a bronchointerstitial pattern. Faecal samples collected over 3 days were positive for Angiostrongylus vasorum after examination using the Baermann lungworm test. The A. vasorum infection was successfully treated with fenbendazole, whereupon thrombocytopenia and prolonged coagulation times were resolved. In regions of low prevalence, an infection with A. vasorum should also be considered as a differential diagnosis in dogs with coagulation abnormalities. Respiratory signs can be absent with this disease. The patient may have acquired the infection abroad or in Germany.

Computed tomographic features of basihyoid ectopic thyroid carcinoma in dogs.

Eight dogs with a firm, nonpainful swelling in the ventral laryngeal region and with a final diagnosis of ectopic thyroid carcinoma were investigated by Computed Tomography (CT) at six different institutions. Computed Tomography findings were reviewed, focusing on lesion volume, shape, margins, relationship with surrounding structures and adjacent vessels, attenuation characteristics, and presence of metastases. Ectopic thyroid carcinomas were seen as oval-to-bilobed masses centered on the basihyoid bone with associated bone lysis, highly vascularized capsules with central poorly contrast enhancing areas. In all cases there was laryngeal wall infiltration, in two dogs invasion of the laryngeal lumen and in one case invasion of the ventral muscular and subcutaneous plane. Metastases were found in retropharyngeal lymph nodes (three cases) and in the lung (two cases). Ectopic thyroid carcinoma should be considered in the differential diagnosis when a mass in the basihyoid region is present. Described CT features may be typical for ectopic thyroid neoplasia and could be used to help decide the therapeutic plan.

National assessment of validity of coding of acute mastoiditis: a standardised reassessment of 1966 records.

OBJECTIVES: To investigate the internal validity of the diagnosis code used at discharge after treatment of acute mastoiditis. DESIGN: Retrospective national re-evaluation study of patient records 1993-2007 and make comparison with the original ICD codes. SETTING: All ENT departments at university hospitals and one large county hospital department in Sweden. PARTICIPANTS: A total of 1966 records were reviewed for patients with ICD codes for in-patient treatment of acute (529), chronic (44) and unspecified mastoiditis (21) and acute otitis media (1372). MAIN OUTCOME MEASURES: ICD codes were reviewed by the authors with a defined protocol for the clinical diagnosis of acute mastoiditis. Those not satisfying the diagnosis were given an alternative diagnosis. RESULTS: Of 529 records with ICD coding for acute mastoiditis, 397 (75%) were found to meet the definition of acute mastoiditis used in this study, while 18% were not diagnosed as having any type of mastoiditis after review. Review of the in-patients treated for acute media otitis identified an additional 60 cases fulfilling the definition of acute mastoiditis. Overdiagnosis was common, and many patients with a diagnostic code indicating acute mastoiditis had been treated for external otitis or otorrhoea with transmyringeal drainage. CONCLUSIONS: The internal validity of the diagnosis acute mastoiditis is dependent on the use of standardised, well-defined criteria. Reliability of diagnosis is fundamental for the comparison of results from different studies. Inadequate reliability in the diagnosis of acute mastoiditis also affects calculations of incidence rates and statistical power and may also affect the conclusions drawn from the results.

Generating anatomical models of the heart and the aorta from medical images for personalized physiological simulations.

The anatomy and motion of the heart and the aorta are essential for patient-specific simulations of cardiac electrophysiology, wall mechanics and hemodynamics. Within the European integrated project euHeart, algorithms have been developed that allow to efficiently generate patient-specific anatomical models from medical images from multiple imaging modalities. These models, for instance, account for myocardial deformation, cardiac wall motion, and patient-specific tissue information like myocardial scar location. Furthermore, integration of algorithms for anatomy extraction and physiological simulations has been brought forward. Physiological simulations are linked closer to anatomical models by encoding tissue properties, like the muscle fibers, into segmentation meshes. Biophysical constraints are also utilized in combination with image analysis to assess tissue properties. Both examples show directions of how physiological simulations could provide new challenges and stimuli for image analysis research in the future.

Population pharmacokinetic modeling for dose setting of nonacog beta pegol (N9-GP), a glycoPEGylated recombinant factor IX.

BACKGROUND: nonacog beta pegol (N9-GP) is a glycoPEGylated recombinant factor IX (rFIX) molecule with a prolonged half-life. OBJECTIVES: To provide information on potential dose regimens for N9-GP for phase 3 pivotal and surgery trials. METHODS: A population pharmacokinetic model was developed from single-dose data derived from the first human-dose trial with N9-GP in hemophilia B patients, and was used to extrapolate to steady-state conditions for different N9-GP dose regimens for prophylaxis. The model was also used to compare prophylaxis using N9-GP with standard prophylactic regimens using rFIX or plasma-derived (pd) FIX (40 IU kg(-1) every third day). Plasma activity following dosing with N9-GP, rFIX and pdFIX for surgery and on-demand treatment of bleeds was also simulated. RESULTS: A linear two-compartmental model best described the pharmacokinetic profiles of N9-GP, rFIX and pdFIX. A prophylactic regimen of 10 U kg(-1) N9-GP once weekly predicted mean peak and trough levels of 18 and 4.2 U dL(-1) , while 40 U kg(-1) once weekly predicted values of 72 and 17 U dL(-1) , respectively. Standard prophylactic regimens with rFIX and pdFIX predicted mean peak and trough levels of 34 and 3.9 IU dL(-1) for rFIX, and mean values of 43 and 2.1 IU dL(-1) for pdFIX. Additional simulations predicted significantly reduced dosing frequency and factor concentrate consumption for N9-GP vs. rFIX and pdFIX for surgery and the treatment of bleeds. CONCLUSIONS: N9-GP may allow prophylaxis, surgical dosing regimens and on-demand treatment of bleeding episodes with less frequent injections and lower factor concentrate consumption; this possibility is being investigated in prospective clinical trials.

Distribution of flunixin meglumine and firocoxib into aqueous humor of horses.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used systemically for the treatment of inflammatory ocular disease in horses. However, little information exists regarding the ocular penetration of this class of drugs in the horse. OBJECTIVE: To determine the distribution of orally administered flunixin meglumine and firocoxib into the aqueous humor of horses. ANIMALS: Fifteen healthy adult horses with no evidence of ophthalmic disease. METHODS: Horses were randomly assigned to a control group and 2 treatment groups of equal sizes (n = 5). Horses assigned to the treatment groups received an NSAID (flunixin meglumine, 1.1 mg/kg PO q24h or firocoxib, 0.1 mg/kg PO q24h for 7 days). Horses in the control group received no medications. Concentrations of flunixin meglumine and firocoxib in serum and aqueous humor and prostaglandin (PG) E(2) in aqueous humor were determined on days 1, 3, and 5 and aqueous : serum ratios were calculated. RESULTS: Firocoxib penetrated the aqueous humor to a significantly greater extent than did flunixin meglumine at days 3 and 5. Aqueous : serum ratios were 3.59 ± 3.32 and 11.99 ± 4.62% for flunixin meglumine and firocoxib, respectively. Ocular PGE(2) concentrations showed no differences at any time point among study groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Both flunixin meglumine and firocoxib penetrated into the aqueous humor of horses. This study suggests that orally administered firocoxib penetrates the aqueous humor better than orally administered flunixin meglumine at label dosages in the absence of ocular inflammation. Firocoxib should be considered for the treatment of inflammatory ophthalmic lesions in horses at risk for the development of adverse effects associated with nonselective NSAID administration.

Evidence of the development of 'domain-restricted' expertise in the recognition of asymmetric motion characteristics of hindlimb lameness in the horse.

REASONS FOR PERFORMING STUDY: Visual assessment of horses' movements is subjective, affected by bias and dependent on the level of experience of the assessor. However, to date there are no data available on the ability of the human visual system to recognise (a)symmetry in moving objects. OBJECTIVES: To investigate, using visual lameness assessment, the limits of human perception and the ability of experienced and nonexperienced individuals to detect asymmetry in 2 moving objects simulating hindlimb lameness in the horse. METHODS: Twelve experienced individuals (equine and small animal clinicians), and 24 nonexperienced individuals (undergraduate veterinary students) were presented with computer simulations showing 2 'tuber coxae markers' created using data from both lame and nonperceptibly lame horses, as well as artificial data based on a sine wave. Individuals were asked to classify as symmetrical or asymmetrical, and then rank based on the grade of perceived asymmetry. Repeatability and learning effect were evaluated by repeating the tests on a subset of subjects. RESULTS: The threshold for detection of movement asymmetry was found to be approximately 25% difference in amplitude between the 2 moving objects for all individuals. There was no significant difference between experienced and nonexperienced individuals in the ability to detect asymmetry in the simulations based on artificial data. However, the percentage of correct answers was higher for experienced compared to nonexperienced individuals for simulations based on data from real lame horses. CONCLUSIONS: There was a significant difference between experienced and nonexperienced individuals in the ability to identify asymmetric movement based on the pattern seen in a lame horse, as opposed to an artificial pattern for which all individuals showed similar performance. POTENTIAL RELEVANCE: The study provides the basis for the development of computer simulations that could aid in training veterinarians in the diagnosis of lameness and, even, the objective assessment of expertise in this field.

Intra- and interobserver agreement in the interpretation of navicular bones on radiographs and computed tomography scans.

REASONS FOR PERFORMING STUDY: Criteria for the radiographic evaluation of navicular bones in horses have been published to standardise classification of radiographic signs. However, intra- and interobserver agreement have not been established. OBJECTIVE: To determine intra- and interobserver agreement in the evaluation of radiographic and computed tomographic (CT) navicular changes. It was hypothesised that: 1) intraobserver agreement would be better than interobserver agreement; 2) agreement would be better for CT than for radiography; and 3) pathological changes would be recognised with greater certainty with CT. METHODS: Radiographs and CT scans of 60 cadaver navicular bones were evaluated by 3 observers using published criteria. A subset of 30 studies was evaluated twice by one observer. Agreement was tested using the kappa statistic. Certainty about pathological changes was evaluated by giving the observers the option to choose 'not sure'. RESULTS: Agreement varied from poor to almost perfect for radiographic evaluation and from poor to substantial for CT evaluation. For radiographic evaluation mean interobserver agreement was fair, as it was for CT evaluation. For radiographic evaluation mean intraobserver agreement was moderate as it was for CT evaluation. Pathological changes were evaluated with greater certainty on CT scans compared to radiographs; however, this was not associated with improved agreement. CONCLUSIONS: Variations in classification of navicular lesions in radiographic and CT studies were considerable between and within observers and challenge the use of such studies for diagnostic and prognostic purposes. POTENTIAL RELEVANCE: The results of this study allowed the identification of evaluation criteria with sufficient precision to be useful for navicular bone evaluation.

Spectrum of computed tomographic findings in 58 canine elbows with fragmentation of the medial coronoid process.

OBJECTIVE: To describe in detail the computed tomographic findings in elbows of dogs with fragmentation of the medial coronoid process of the ulna. METHODS: Retrospective review of computed tomographic images of 58 elbows that had displaced medial coronoid process fragment(s), non-displaced medial coronoid process fragment or a stable fissure in the articular cartilage of the medial coronoid process at arthroscopy. RESULTS: Bone fragments were observed in 85 per cent elbows with a displaced fragment at arthroscopy, in 18 per cent elbows with a non-displaced fragment and in 29 per cent elbows with a stable fissure. Fissures in the subchondral bone were observed in computed tomographic images of 43 per cent elbows that had a stable fissure at arthroscopy. Abnormal shape, sclerosis and lucency affecting the medial coronoid process, subchondral sclerosis of the ulna and humerus, irregular radial incisure of the ulna and periarticular osteophytes were observed in a similar proportion in dogs regardless of the arthroscopic findings. Kissing lesions affecting the medial aspect of the humeral condyle were mainly associated with displaced fragments. Signs of joint incongruity were observed in dorsal and sagittal reconstructed computed tomographic images in 24 per cent elbows. CLINICAL SIGNIFICANCE: A wide range of abnormalities may be observed in computed tomographic images of dogs with fragmented medial coronoid process. Computed tomographic is moderately sensitive for detection of fragments.

Sulforaphane targets pancreatic tumour-initiating cells by NF-kappaB-induced antiapoptotic signalling.

BACKGROUND AND AIMS: Emerging evidence suggests that highly treatment-resistant tumour-initiating cells (TICs) play a central role in the pathogenesis of pancreatic cancer. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered to be a novel anticancer agent; however, recent studies have shown that many pancreatic cancer cells are resistant to apoptosis induction by TRAIL due to TRAIL-activated nuclear factor-kappaB (NF-kappaB) signalling. Several chemopreventive agents are able to inhibit NF-kappaB, and favourable results have been obtained--for example, for the broccoli compound sulforaphane-in preventing metastasis in clinical studies. The aim of the study was to identify TICs in pancreatic carcinoma for analysis of resistance mechanisms and for definition of sensitising agents. METHODS: TICs were defined by expression patterns of a CD44(+)/CD24(-), CD44(+)/CD24(+) or CD44(+)/CD133(+) phenotype and correlation to growth in immunodeficient mice, differentiation grade, clonogenic growth, sphere formation, aldehyde dehydrogenase (ALDH) activity and therapy resistance. RESULTS: Mechanistically, specific binding of transcriptionally active cRel-containing NF-kappaB complexes in TICs was observed. Sulforaphane prevented NF-kappaB binding, downregulated apoptosis inhibitors and induced apoptosis, together with prevention of clonogenicity. Gemcitabine, the chemopreventive agents resveratrol and wogonin, and the death ligand TRAIL were less effective. In a xenograft model, sulforaphane strongly blocked tumour growth and angiogenesis, while combination with TRAIL had an additive effect without obvious cytotoxicity in normal cells. Freshly isolated patient tumour cells expressing markers for TICs could be sensitised by sulforaphane for TRAIL-induced cytotoxicity. CONCLUSION: The data provide new insights into resistance mechanisms of TICs and suggest the combination of sulforaphane with TRAIL as a promising strategy for targeting of pancreatic TICs.

Recombinant human bone morphogenetic protein-2 for grade III open segmental tibial fractures from combat injuries in Iraq.

This is a retrospective consecutive case series of 138 Gustillo-Anderson type IIIB and IIIC segmental tibial fractures treated at Walter Reed Army Medical Center in soldiers injured in Iraq between March 2003 and March 2005. Five patients with a head injury and four who were lost to follow-up were excluded. The patients were treated definitively with either a ringed external fixator or a reamed intramedullary nail, evaluated in terms of supplementary bone grafting with either autogenous bone (group 1, 67 patients) or recombinant human bone morphogenetic protein-2 at 1.50 mg/ml applied to an absorbable collagen sponge (group 2, 62 patients). The mechanism of injury, defect size and classification, associated injuries, presence of infection, preliminary treatment/fixation, number of procedures before definitive management, time to and details of definitive management, subsequent infection, re-operation, smoking history and other complications were noted. Radiographs were assessed for union, delayed union or nonunion by an independent investigator. All the patients were male. Their mean age was 26.6 years (20 to 42) and the mean follow-up was for 15.6 months (12 to 32). Group 2 had a slightly higher profile of concomitant injuries and a slightly worse fracture classification, but these were not significant. The rate of union was 76% (51 of 67) for group 1 and 92% for group 2 (57 of 62; p = 0.015). There was also a higher rate of subsequent infection in group 1 (14.9%) compared with group 2 (3.2%; p = 0.001) and a higher rate of re-operation (28%) in group 1 (p = 0.003). There were no observed hypersensitivity reactions to the recombinant human bone morphogenetic protein-2 implant.

VEGF expression by mesenchymal stem cells contributes to angiogenesis in pancreatic carcinoma.

Little is known about the factors that enable the mobilisation of human mesenchymal stem cells (MSC) from the bone marrow into the blood stream and their recruitment to and retention in the tumour. We found specific migration of MSC towards growth factors present in pancreatic tumours, such as PDGF, EGF, VEGF and specific inhibitors Glivec, Erbitux and Avastin interfered with migration. Within a few hours, MSC migrated into spheroids consisting of pancreatic cancer cells, fibroblasts and endothelial cells as measured by time-lapse microscopy. Supernatant from subconfluent MSC increased sprouting of HUVEC due to VEGF production by MSC itself as demonstrated by RT-PCR and ELISA. Only few MSCs were differentiated into endothelial cells in vitro, whereas in vivo differentiation was not observed. Lentiviral GFP-marked MSCs, injected in nude mice xenografted with orthotopic pancreatic tumours, preferentially migrated into the tumours as observed by FACS analysis of green fluorescent cells. By immunofluorescence and intravital microscopic studies, we found the interaction of MSC with the endothelium of blood vessels. Mesenchymal stem cells supported tumour angiogenesis in vivo, that is CD31(+) vessel density was increased after the transfer of MSC compared with siVEGF-MSC. Our data demonstrate the migration of MSC toward tumour vessels and suggest a supportive role in angiogenesis.

Improved lentiviral transduction of human mesenchymal stem cells for therapeutic intervention in pancreatic cancer.

Genetic modification of human bone marrow mesenchymal stem cells (MSC) is highly valuable for their exploitation in basic science and therapeutic applications, for example in cancer. We present here a new, fast and easy-to-use method to enrich a functional population of lentiviral (LV)-transduced MSC expressing enhanced green fluorescent protein (eGFP). We replaced the eGFP gene by a fusion gene of puromycin acetyltransferase and eGFP. Upon LV gene transfer and puromycin selection, we quickly obtained a pure transduced MSC population, in which growth, differentiation capacity and migration preferences were not compromised. Furthermore, we are the first to report the migration velocity of MSC among which 30% were moving and velocity of about 15 mum h(-1) was not altered by LV transduction. Manipulated MSC underwent senescence one passage earlier than non-transduced cells, suggesting the use for therapeutic intervention in early passage numbers. Upon tail vein application in nude mice, the majority of LV-transduced MSC could be detected in human orthotopic pancreatic tumor xenografts and to a minor extent in mouse liver, kidney and lung. Together, LV transduction of genes to MSC followed by puromycin selection is a powerful tool for basic research and improves the therapeutic prospects of MSC as vehicles in gene therapy.