[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.

[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.

Diagnosis and surgical management of an extraskeletal osteosarcoma of the brachial plexus in a Belgian shepherd dog.

An 11-year-old Belgian shepherd presented with progressive right thoracic limb lameness. Computed tomography and magnetic resonance imaging revealed a brachial plexus neoplasm and cytology was suggestive of a sarcoma. The patient underwent forequarter amputation and hemilaminectomy of the fifth cervical to first thoracic vertebrae with nerve root transection. Histopathology confirmed extraskeletal osteosarcoma. Twelve months post-operatively, the dog was exercising normally, and computed tomography did not identify local recurrence or metastatic disease. This is the first recorded case of canine brachial plexus extraskeletal osteosarcoma.

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.

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.

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.

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.

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.

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.

Mammalian genomes contain active recombinase recognition sites.

Recombinases derived from microorganisms mediate efficient site-specific recombination. For example, the Cre recombinase from bacteriophage P1 efficiently carries out recombination at its loxP target sites. While this enzyme can function in mammalian cells, the 34bp loxP site is expected to be absent from mammalian genomes. We have discovered that sequences from the human and mouse genomes surprisingly divergent from loxP can support Cre-mediated recombination at up to 100% of the efficiency of the native loxP site in bacterial assays. Transient assays in human cells demonstrate that such pseudo-lox sites also support Cre-mediated integration and excision in the human cell environment. Pseudo sites for Cre and other recombinases may be useful for site-specific insertion of exogenous genes into mammalian genomes during gene therapy and other genetic engineering processes.

Male rape: offenders and victims.

In an analysis of 22 cases of male rape in a community setting, the gender of the victim did not appear to be of primary importance to some of the rapists, but for others, males appeared to be specific intended targets, and the rapists' assaults were an effort to deal with unresolved and conflictual aspects of their lives. For all offenders the sexual assault was an act of retaliation, an expression of power, and an assertion of their strength and manhood. The impact of rape on the male victims was similar to that on female victims, disrupting their biopsychosocial functioning; however, male rape appears to be underreported due to the stigma associated with it.

Rape: power, anger, and sexuality.

Accounts from both offenders and victims of what occurs during a rape suggest that issues of power, anger, and sexuality are important in understanding the rapist's behavior. All three issues seem to operate in every rape, but the proportion varies and one issue seems to dominate in each instance. The authors ranked accounts from 133 offenders and 92 victims for the dominant issue and found that the offenses could be categorized as power rape (sexuality used primarily to express power) or anger rape (use of sexuality to express anger). There were no rapes in which sex was the dominant issue; sexuality was always in the service of other, nonsexual needs.

[Magnetic resonance imaging in screening for bone metastasis? A prospective comparison with bone scintigraphy]. / Kernspintomographie zum Metastasen-Screening? Ein prospektiver Vergleich mit der Skelettszintigraphie.

To define the value of magnetic resonance imaging (MRI) in screening for bone metastases (BM) compared to bone scintigraphy (BSc) 102 patients with tumours with frequent BM were examined also by MRI of spine, pelvis, femora, and proximal tibiae. All patients had normal BSc and 96 (94%) normal MRI. Only 6% of the patients had focal abnormalities within the bone marrow. This indicates that there is a 94% probability of absence of BM if BSc is normal. Therefore, BSc should currently remain the method of choice for screening for BM. Despite MRI is sensitive and specific, with the common technique up to now it should not be used instead of BSc in screening because of costs, duration, and lack of whole body examination. MRI is a valuable adjunct in equivocal findings in BSc with negative results on radiographs.

Eustachian tube function in otitis-prone and healthy children.

To evaluate the significance of Eustachian tube function in recurrent acute otitis media (rAOM), 50 otitis-prone children (greater than 11 episodes of AOM) were compared with 49 children without rAOM. Tubal function tests were: initial middle-ear pressure, active tubal function (muscular opening function), passive function (pressure opening and closing levels), and inflationary and deflationary capacity. The otitis-prone children were found to have significantly poorer active tubal function than controls. Other test results did not differ between the two groups. The otitis-prone children were also divided into subgroups with and without intermittent secretory otitis media (SOM), and with and without allergy, but no differences in tubal function tests were found between the different subgroups. The findings suggest active tubal function to be the most significant variable regarding proneness to rAOM, but not to distinguish between particular subgroups of otitis-prone children. The available technique for testing Eustachian tube function is insufficiently sensitive, however, to be conclusive in individual cases, and it is still not possible to predict individual outcome of the illness from tubal function test results alone.

Continuous long-term measurements of the middle ear pressure in subjects without a history of ear disease.

A new method was used for continuous measurement of the middle ear (ME) pressure during a 24-h period. In 10 subjects without a history of ear disease a small perforation was made through the tympanic membrane. A tight rubber stopper containing a small polyethylene tube was fitted into the external ear canal. Conventional tubal function tests were performed. The equipment was then carried by the subjects for 24 h of normal activity to monitor any slow or rapid dynamic pressure change in the ME. Body position was found to be the most important factor affecting ME pressure variation, during the 24-h continuous pressure measurements. A significant pressure rise occurred in the recumbent position in all but one subject. Few rapid pressure equilibrations were seen during the recordings, indicating few tubal openings. This implies that the pressure changes in the ME seen in this study were mainly the result of gas exchange over the mucosa. The investigation might be a base for reference when investigating different kinds of pathologic conditions in the ear.