Altered Regulation of mRNA and miRNA Expression in Epithelial and Stromal Tissue of Keratoconus Corneas

PurposeEvaluation of mRNA and microRNA (miRNA) expression in epithelium and stroma of patients with keratoconus.MethodsThe epithelium and stroma of eight corneas of eight patients with keratoconus and eight corneas of eight non-keratoconus healthy controls were studied separately. RNA was extracted, and mRNA and miRNA analyses were performed using microarrays. Differentially expressed mRNAs and miRNAs in epithelial and stromal keratoconus samples compared to healthy controls were identified. Selected genes and miRNAs were further validated using RT-qPCR.ResultsWe discovered 170 epithelial and 1498 stromal deregulated protein-coding mRNAs in KC samples. In addition, in epithelial samples 180 miRNAs and in stromal samples 379 miRNAs were significantly deregulated more than twofold compared to controls. Pathway analysis revealed enrichment of metabolic and axon guidance pathways for epithelial cells and enrichment of metabolic, mitogen-activated protein kinase (MAPK), and focal adhesion pathways for stromal cells.ConclusionsThis study demonstrates significant differences in the expression and regulation of mRNAs and miRNAs in the epithelium and stroma of Patients with KC. Also, in addition to the well-known target candidates, we were able to identify further genes and miRNAs that may be associated with keratoconus. Signaling pathways influencing metabolic changes and cell contacts are affected in epithelial and stromal cells of patients with keratoconus.     

CT-guided high-dose-rate brachytherapy of unresectable hepatocellular carcinoma

Strahlentherapie und Onkologie - The purpose of the present study was to evaluate the clinical outcome of CT-guided high-dose-rate brachytherapy (CT-HDRBT) in patients with unresectable...     

Gadoxetic acid enhanced MRI for differentiation of FNH and HCA: a single centre experience

Objectives

Evaluation of enhancement characteristics of histopathologically confirmed focal nodular hyperplasias (FNHs) and hepatocellular adenomas (HCAs) with gadoxetic acid-enhanced MRI.

Methods

Sixty-eight patients with 115 histopathologically proven lesions (FNHs, n?=?44; HCAs, n?=?71) examined with gadoxetic acid-enhanced MRI were retrospectively enrolled (standard of reference: surgical resection, n?=?53 patients (lesions: FNHs, n?=?37; HCAs, n?=?53); biopsy, n?=?15 (lesions: FNHs, n?=?7; HCAs, n?=?18)). Two radiologists evaluated all MR images regarding morphological features as well as the vascular and hepatocyte-specific enhancement in consensus.

Results

For the hepatobiliary phase, relative enhancement of the lesions and lesion to liver enhancement were significantly lower for HCAs (mean, 48.7 (±48.4) % and 49.4 (±33.9) %) compared to FNHs (159.3 (±92.5) %; and 151.7 (±79) %; accuracy of 89 % and 90 %, respectively; P?<?0.001). Visual strong uptake of FNHs vs. hypointensity of HCAs in the hepatobiliary phase resulted in an accuracy of 92 %. This parameter was superior to all other morphological and dynamic vascular criteria alone and in combination (accuracy, 54–85 %).

Conclusions

For differentiation of FNHs and HCAs by means of MRI, gadoxetic acid uptake in the hepatobiliary phase was found to be superior to all other criteria alone and in combination.

Key Points

? EOB-MRI is well suited to differentiate FNHs and hepatocellular adenomas. ? For this purpose hepatobiliary phase is superior to unenhanced and dynamic imaging. ? Hepatobiliary phase (peripheral) hyper- or isointensity is typical for FNH. ? Hepatobiliary phase hypointensity is typical for hepatocellular adenomas. ? EOB-MRI helps to avoid misinterpretations of benign hepatocellular lesions.     

The frontal pelvic plane provides a valid reference system for implantation of the acetabular cup: spatial orientation of the pelvis in different positions

Background The frontal pelvic plane has traditionally served as the reference plane for implantation of the acetabular cup during total hip arthroplasty, with referencing performed with the patient supine on the operating table. During daily activities in an upright position, the frontal pelvic plane changes from a horizontal to a vertical orientation. If this change in orientation is accompanied by a substantial change in pelvic inclination angle, it would mean that the use of the frontal pelvic plane as a reference plane for implantation of the acetabular cup would not be valid for proper alignment of the cup. To evaluate this possibility, we measured the change of inclination of the pelvis from the supine to the standing position.

Subjects and methods We evaluated 120 patients, first positioned in a standing position and then supine on a table. Three pelvic landmarks were digitized percutaneously, and the spatial coordinates were calculated with regard to pelvic orientation in the horizontal and the vertical plane.

Results We found a mean inclination of 6.7° in the standing position and 5.6° in the supine position. Patients who were more than 60 years of age who did not have coxarthrosis had a greater inclination angle (8.7°) while standing. Pelvic orientation was stable with regard to the supine and standing positions. These results were independent of sex, level of arthrosis, or status after implantation of a total hip replacement.

Interpretation The frontal pelvic plane is a valid reference plane for implantation of the acetabular cup.

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Validation of the EORTC QLQ-C30 and EORTC QLQ-H&N35 in patients with laryngeal cancer after surgery

Background.

The aim of this study was to test the validity of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core Module (QLQ‐C30) and Head and Neck Module (QLQ‐H&N35) for patients who have undergone surgery due to laryngeal cancer.

Methods.

A total of 323 patients from 6 different centers in Germany who had been operated on completed the QLQ‐C30 and the QLQ‐H&N35 in addition to being surveyed in a personal interview.

Results.

Multitrait scaling analysis confirmed the proposed scale structure of both questionnaires. Cronbach's alpha of the QLQ‐C30 scales ranged from 0.64 (Cognitive Functioning) to 0.94 (Global Health Status); the alpha of the QLQ‐H&N35 ranged from 0.55 (Speech) to 0.90 (Sexuality). Known‐groups comparisons showed multiple differences in sociodemographic and clinical variables.

Conclusion.

It can be concluded that the QLQ‐H&N35, in conjunction with the QLQ‐C30, is a reliable instrument that is able to differentiate between diverse groups of patients with laryngeal cancer after surgery. © 2008 Wiley Periodicals, Inc. Head Neck, 2009     

Mn-DPDP–enhanced MR imaging of malignant liver lesions: Efficacy and safety in 20 patients

Twenty patients with malignant liver lesions underwent magnetic resonance (MR) imaging with manganese (II) DPDP [N,N′-dipyridoxylethylenediamine-N,N′-diacetate 5,5′-bis(phosphate)] to evaluate the safety and efficacy of the contrast agent. In two groups of 10 patients each, 5 μmol/kg Mn-DPDP was administered intravenously (3 mL/min) at a concentration of either 50 or 10 μmol/mL. T1- and T2-weighted images were obtained with a 1.5-T imager. Six patients reported a total of eight instances of side effects (flush, feeling of warmth, metallic taste) of which seven occured at the 50 μmol/mL concentration. A significant decrease in alkaline phosphatase levels 2 hours after injection was recorded. On T1-weighted images, the 10 μmol/mL formulation yielded significantly greater increases in contrast-to-noise ratio (79.8%–137.5%) than the 50 μmol/mL formulation (46.2%–86.6%). In a blinded reader study of 10 patients with one to five lesions each, no lesion was missed on Mn-DPDP–enhanced T1-weighted images; however, four false-positive foci were identified. The authors conclude that slow administration of 5 μmol/kg Mn-DPDP at a concentration of 10 μmol/mL is safe and efficient enough to proceed to further clinical trials.     

High-dose Remifentanil Does Not Impair Cerebrovascular Carbon Dioxide Reactivity in Healthy Male Volunteers

Background: Cerebrovascular carbon dioxide reactivity during high-dose remifentanil infusion was investigated in volunteers by measurement of regional cerebral blood flow (rCBF) and mean CBF velocity (CBFv).

Methods: Ten healthy male volunteers with a laryngeal mask for artificial ventilation received remifentanil at an infusion rate of 2 and 4 [mu]g [middle dot] kg-1 [middle dot] min-1 under normocapnia, hypocapnia, and hypercapnia. Stable xenon-enhanced computed tomography and transcranial Doppler ultrasonography of the left middle cerebral artery were used to assess rCBF and mean CBFv, respectively. If required, blood pressure was maintained within baseline values with intravenous phenylephrine to avoid confounding effects of altered hemodynamics.

Results: Hemodynamic parameters were maintained constant over time. Remifentanil infusion at 2 and 4 [mu]g [middle dot] kg-1 [middle dot] min-1 significantly decreased rCBF and mean CBFv. Both rCBF and mean CBFv increased as the arterial carbon dioxide tension increased from hypocapnia to hypercapnia, indicating that cerebrovascular reactivity remained intact. The average slopes of rCBF reactivity were 0.56 +/- 0.27 and 0.49 +/- 0.28 ml [middle dot] 100 g-1 [middle dot] min-1 [middle dot] mmHg-1 for 2 and 4 [mu]g[middle dot]kg-1[middle dot]min-1 remifentanil, respectively (relative change in percent/mmHg: 1.9 +/- 0.8 and 1.6 +/- 0.5, respectively). The average slopes for mean CBFv reactivity were 1.61 +/- 0.95 and 1.54 +/- 0.83 cm [middle dot] s-1 [middle dot] mmHg-1 for 2 and 4 [mu]g [middle dot] kg-1 [middle dot] min-1 remifentanil, respectively (relative change in percent/mmHg: 1.86 +/- 0.59 and 1.79 +/- 0.59, respectively). Preanesthesia and postanesthesia values of rCBF and mean CBFv did not differ.     

Radiographic versus ultrasound evaluation of the Risser Grade in adolescent idiopathic scoliosis: a prospective study of 46 patients

The determination of skeletal age is essential in the management of patients with scoliosis. One of the most frequently used techniques to determine skeletal maturity is the method described by Risser. However, repeated X-ray exposure in the follow-up examinations of scoliosis patients may increase the risk of cancer. We compared conventional radiological evaluation of the Risser grade with ultrasound evaluation. For scoliosis patients routine application of ultrasound in the follow-up examinations may significantly reduce radiation exposure. 46 adolescent idiopathic scoliosis patients (median age, 14.5 years) were investigated. Sonographic and radiographic assessment of Risser sign was carried out by two independent senior staff skeletal radiologists. Agreement of Risser Grade between the two diagnostic methods was determined by Kappa statistics. Coefficients <0.21, 0.21–0.40, 0.41–0.60, 0.61–0.80, and >0.80 were rated as poor, fair, moderate, good, and very good agreement. For Risser Grades I–III 100% agreement was found between the two methods. Disagreement between radiographic and sonographic evaluation was found in Risser Grades IV and V. In five patients, X-ray evaluation yielded Risser Grade V while ultrasound showed Risser Grade IV. In one patient, radiographic examination resulted in Risser Grade IV while Grade V was detected in ultrasound. Overall, the Kappa value showed very good agreement between the two diagnostic methods. Our findings suggest that ultrasound can be applied as an alternative method to X-ray evaluation in Risser Grade determination. It should be routinely used in clinical practice to reduce the patients exposure to radiation.     

Local cooling reduces regional bone blood flow

Local cooling is very common after bone and joint surgery. Therefore the knowledge of bone blood flow during local cooling is of substantial interest. Previous studies revealed that hypothermia leads to vasoconstriction followed by decreased blood flow levels. The aim of this study was to characterize if local cooling is capable of inducing reduced blood flow in bone tissue using a stepwise‐reduced temperature protocol in experimental rabbits. To examine bone blood flow we utilized the fluorescent microsphere (FM) method. In New Zealand white rabbits one randomly chosen hind limb was cooled stepwise from 32 to 2°C, whereas the contra lateral hind limb served as control. Injection of microspheres was performed after stabilization of bone and muscle temperature at each temperature level. Bones were removed, dissected and fluorescence intensity was determined to calculate blood flow values. We found that blood flow of all cooled regions decreased relative to the applied external temperature. At maximum cooling blood flow was almost completely disrupted, indicating local cooling as powerful regulatory mechanism for regional bone blood flow (RBBF). Postoperative cooling therefore may lead to strongly decreased bone blood flow values. As a result external cooling has capacity to both diminish bone healing and reduce bleeding complications. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1820–1827, 2013