Mutations in the tight-junction gene claudin 19 (CLDN19) are associated with renal magnesium wasting, renal failure, and severe ocular involvement

Claudins are major components of tight junctions and contribute to the epithelial-barrier function by restricting free diffusion of solutes through the paracellular pathway. We have mapped a new locus for recessive renal magnesium loss on chromosome 1p34.2 and have identified mutations in CLDN19, a member of the claudin multigene family, in patients affected by hypomagnesemia, renal failure, and severe ocular abnormalities. CLDN19 encodes the tight-junction protein claudin-19, and we demonstrate high expression of CLDN19 in renal tubules and the retina. The identified mutations interfere severely with either cell-membrane trafficking or the assembly of the claudin-19 protein. The identification of CLDN19 mutations in patients with chronic renal failure and severe visual impairment supports the fundamental role of claudin-19 for normal renal tubular function and undisturbed organization and development of the retina.

A novel multiple-trauma CT-scanning protocol using patient repositioning

Emergency CT examination is considered to be a trade-off between a short scan time and the acceptance of artifacts. This study evaluates the influence of patient repositioning on artifacts and scan time. Eighty-three consecutive multiple-trauma patients were included in this prospective study. Patients were examined without repositioning (group 1, n=39) or with patient rotation to feet-first with arms raised for scanning the chest and abdomen/pelvis (group 2, n=44). The mean scan time was 21 min in group 1 and 25 min in group 2 (P=0.01). The mean repositioning time in group 2 was 8 min. Significantly, more artifacts were observed in group 1 (with a repeated scan in 7%) than in group 2 (P=0.0001). This novel multiple- trauma CT-scanning protocol with patient repositioning achieves a higher image quality with significantly fewer artifacts than without repositioning but increases scan time slightly.

Computer-assisted arthroplasty using bioengineered autografts

Recent advances in tissue-engineered cartilage open the door to new clinical treatments of joint lesions. Common to all therapies with in-vitro-engineered autografts is the need for optimal fit of the construct to allow screwless implantation and optimal integration into the live joint. Computer-assisted surgery (CAS) techniques are prime candidates to ensure the required accuracy, while at the same time simplifying the procedure. A pilot study has been conducted aiming at assembling a new set of methods to support ankle joint arthroplasty using bioengineered autografts. Computer assistance allows planning of the implant shape on a computed tomography (CT) image, manufacturing the construct according to the plan, and interoperatively navigating the surgical tools for implantation. A rotational symmetric model of the joint surface was used to avoid segmentation of the CT image; new software was developed to determine the joint axis and make the implant shape parameterizable. A complete cycle of treatment from planning to operation was conducted on a human cadaveric foot, thus proving the feasibility of computer-assisted arthroplasty using bioengineered autografts

Magnetic resonance angiography in infrapopliteal arterial disease: prospective comparison of 1.5 and 3 Tesla magnetic resonance imaging

PURPOSE: To prospectively determine the accuracy of 1.5 Tesla (T) and 3 T magnetic resonance angiography (MRA) versus digital subtraction angiography (DSA) in the depiction of infrageniculate arteries in patients with symptomatic peripheral arterial disease. PATIENTS AND METHODS: A prospective 1.5 T, 3 T MRA, and DSA comparison was used to evaluate 360 vessel segments in 10 patients (15 limbs) with chronic symptomatic peripheral arterial disease. Selective DSA was performed within 30 days before both MRAs. The accuracy of 1.5 T and 3 T MRA was compared with DSA as the standard of reference by consensus agreement of 2 experienced readers. Signal-to-noise ratios (SNR) and signal-difference-to-noise ratios (SDNRs) were quantified. RESULTS: No significant difference in overall image quality, sufficiency for diagnosis, depiction of arterial anatomy, motion artifacts, and venous overlap was found comparing 1.5 T with 3 T MRA (P > 0.05 by Wilcoxon signed rank and as by Cohen k test). Overall sensitivity of 1.5 and 3 T MRA for detection of significant arterial stenosis was 79% and 82%, and specificity was 87% and 87% for both modalities, respectively. Interobserver agreement was excellent k > 0.8, P < 0.05) for 1.5 T as well as for 3 T MRA. SNR and SDNR were significantly increased using the 3 T system (average increase: 36.5%, P < 0.032 by t test, and 38.5%, P < 0.037 respectively). CONCLUSIONS: Despite marked improvement of SDNR, 3 T MRA does not yet provide a significantly higher accuracy in diagnostic imaging of atherosclerotic lesions below the knee joint as compared with 1.5 T MRA.

Effects of anatomic conformation on three-dimensional motion of the caudal lumbar and lumbosacral portions of the vertebral column of dogs

OBJECTIVE: To determine the association between the 3-dimensional (3-D) motion pattern of the caudal lumbar and lumbosacral portions of the canine vertebral column and the morphology of vertebrae, facet joints, and intervertebral disks. SAMPLE POPULATION: Vertebral columns of 9 German Shepherd Dogs and 16 dogs of other breeds with similar body weights and body conditions. PROCEDURE: Different morphometric parameters of the vertebral column were assessed by computed tomography (CT) and magnetic resonance imaging. Anatomic conformation and the 3-D motion pattern were compared, and correlation coefficients were calculated. RESULTS: Total range of motion for flexion and extension was mainly associated with the facet joint angle, the facet joint angle difference between levels of the vertebral column in the transverse plane on CT images, disk height, and lever arm length. CONCLUSIONS AND CLINICAL RELEVANCE: Motion is a complex process that is influenced by the entire 3-D conformation of the lumbar portion of the vertebral column. In vivo dynamic measurements of the 3-D motion pattern of the lumbar and lumbosacral portions of the vertebral column will be necessary to further assess biomechanics that could lead to disk degeneration in dogs.

Comparison of different radiography systems in an experimental study for detection of forearm fractures and evaluation of the Müller-AO and Frykman classification for distal radius fractures

OBJECTIVES: We sought to compare the diagnostic performance of screen-film radiography, storage-phosphor radiography, and a flat-panel detector system in detecting forearm fractures and to classify distal radius fractures according to the Müller-AO and Frykman classifications compared with the true extent, depicted by anatomic preparation. MATERIALS AND METHODS: A total of 71 cadaver arms were fractured in a material testing machine creating different fractures of the radius and ulna as well as of the carpal bones. Radiographs of the complete forearm were evaluated by 3 radiologists, and anatomic preparation was used as standard of reference in a receiver operating curve analysis. RESULTS: The highest diagnostic performance was obtained for the detection of distal radius fractures with area under the receiver operating curve (AUC) values of 0.959 for screen-film radiography, 0.966 for storage-phosphor radiography, and 0.971 for the flat-panel detector system (P > 0.05). Exact classification was slightly better for the Frykman (kappa values of 0.457-0.478) compared with the Müller-AO classification (kappa values of 0.404-0.447), but agreement can be considered as moderate for both classifications. CONCLUSIONS: The 3 imaging systems showed a comparable diagnostic performance in detecting forearm fractures. A high diagnostic performance was demonstrated for distal radius fractures and conventional radiography can be routinely performed for fracture detection. However, compared with anatomic preparation, depiction of the true extent of distal radius fractures was limited and the severity of distal radius fractures tends to be underestimated.