In polycystic kidney disease (PKD), erythropoietin (EPO) production and interstitial vascularization are increased compared with other kidney diseases. EPO and several angiogenic factors are controlled by hypoxia-inducible transcription factors (HIFs), which are composed of a constitutive beta-subunit and two alternative alpha-subunits (HIF-1alpha, HIF-2alpha). We hypothesized that cyst expansion may result in pericystic hypoxia and consecutive up-regulation of HIF and thus examined the expression of HIF-alpha and HIF target genes in human PKD and in a rodent PKD model. HIF-1alpha and HIF-2alpha were found to be up-regulated in cyst epithelium and cells of cyst walls, respectively. The distinct expression pattern of the HIF-alpha isoforms closely resembles the respective pattern in normal kidneys under systemic hypoxia. Pimonidazole staining, a marker for tissue hypoxia, confirmed the existence of regional hypoxia in polycystic kidneys. Immunohistochemistry for selected target genes implicated a role for HIF-1alpha in vascular endothelial growth factor and Glut-1 activation and HIF-2alpha in endoglin and EPO stimulation. Polycystin-deficient cells showed physiological, oxygen-dependent HIF-alpha modulation, excluding a direct influence of polycystin deficiency on HIF-alpha regulation. In conclusion, HIF accumulation in human and rat PKD seems to be responsible for increased EPO production and pericystic hypervascularity and may have an impact on progression of PKD.

Our data showed a high variance of the reported neck-shaft angles. Notably, we identified the inconsistency of the published methods of measurement as a central issue. The reported effect of rotation-correction cannot be reliably verified.

Digital templating with external calibration markers is the standard method for planning total hip arthroplasty. We determined the geometrical basis of the magnification effect, compared magnification with external and internal calibration markers, and examined the influence on magnification of the position of the calibration markers, patient weight, and body mass index (BMI). A formula was derived to calculate magnification with internal and external calibration markers, informed by 100 digital radiographs of the pelvis. Intraclass correlations between the measured and calculated values and the strength of relationships between magnification, position and distance of calibration markers and height, weight, and BMI were sought. There was a weak correlation between magnification of internal and external calibration markers (r = 0.297–0.361; p < 0.01). Intraclass correlations were 0.882–1.000 (p = 0.000) for all parameters. There were also weak correlations between magnification of internal and external calibration markers and weight and BMI (r = 0.420, p = 0.000; r = 0.428, p = 0.000, respectively). The correlation between external and internal calibration markers was poor, indicating the need for more accurate calibration methods. While weight and BMI weakly correlated with the magnification of markers, future studies should examine this phenomenon in more detail.

This review emphasizes the prognostic value of spinal MRI for adults with SCIWORA. Using the MRI classification system in future reports will enhance comparability and interpretability and might improve our understanding of the condition.

Background and purposeAdequate restoration of femoral offset (FO) is critical for successful outcome after hip arthroplasty or fixation of hip fracture. Previous studies have identified that hip rotation influences the projected femoral offset (FOP) on plain anteroposterior (AP) radiographs, but the precise effect of rotation is unknown.Patients and methodsWe developed a novel method of assessing rotation-corrected femoral offset (FORC), tested its clinical application in 222 AP hip radiographs following proximal femoral nailing, and validated it in 25 cases with corresponding computed tomography (CT) scans.ResultsThe mean FORC was 57 (29–93) mm, which differed significantly (p < 0.001) from the mean FOP 49 (22–65) mm and from the mean femoral offset determined by the standard method: 49 (23–66) mm. FORC correlated closely with femoral offset assessed by CT (FOCT); the Spearman correlation coefficient was 0.94 (95% CI: 0.88–0.97). The intraclass correlation coefficient for the assessment of FORC by AP hip radiographs correlating the repeated measurements of 1 observer and of 2 independent blinded observers was 1.0 and 1.0, respectively.InterpretationHip rotation affects the FOP on plain AP radiographs of the hip in a predictable way and should be adequately accounted for.

Systematic review, level III.

While anteroposterior pelvis radiographs are susceptible to rotational errors, the coronal reconstruction of the proximal femur in the femoral neck plane allows the correct measurement of the NSA.

The inhibitor of apoptosis protein survivin is of critical importance for regulation of cellular division and survival. Published data point to a restricted function of survivin in embryonic development and cancer; thus survivin has been broadly proposed as an ideal molecular target for specific anti-cancer therapy. In contrast to this paradigm, we report here broad expression of survivin in adult differentiated tissues, as demonstrated at the mRNA and protein levels. Focusing on the kidney, survivin is strongly expressed in proximal tubuli, particularly at the apical membrane, which can be verified in rat, mouse, and human kidneys. In the latter, survivin expression seems to be even stronger in proximal tubuli than in adjacent cancerous tissue. Primary and immortalized human renal tubular cells also showed high levels of survivin protein expression, and RNA interference resulted in a partial G 2 /M arrest of the cell cycle and increased rate of apoptosis. In conclusion, survivin may be of importance for renal pathophysiology and pathology The kidney is an organ with a multitude of highly specific tasks, such as maintenance of water and electrolyte homeostasis, blood pressure control, and regulation of erythropoiesis. For most of these, the tubular system is of crucial importance. Renal tubular cells are very sensitive to a large number of clinically relevant stresses, such as hypoxia/ischemia, sepsis, or different toxic agents. The uniform pathomorphological appearance of such lesions is acute tubular necrosis, which leads to acute renal failure and has profound socio-economical impact, as well as high relevance for mortality of the critically ill patients. In addition, acute tubular injury can contribute to the progression of chronic kidney disease. 1Together with the thick ascending limb of Henle, the proximal tubule is the most sensitive region of the tubular system. Most of the transepithelial transport takes place in the proximal tubule, leading to a very high rate of energy consumption. At the same time the availability of energy substrates is restricted, because tubular cells are not able to perform glycolysis and the peritubular blood supply is easily hampered because of its postcapillary character.2,3 Taken together, the proximal tubule is a functionally important but highly susceptible structure. Considering the delicate nature of the proximal tubulus, its extraordinary ability for repair is remarkable, which involves a high rate of proliferation and differentiation processes potentially leading to complete restoration of