A prospective, single arm study of intraosseous basivertebral nerve ablation for the treatment of chronic low back pain: 12-month results.

Background: The basivertebral nerve (BVN) has been a recently discovered target as a potential source for vertebrogenic chronic low back pain (CLBP). Prior randomized controlled trials have demonstrated safety and efficacy of BVN ablation for vertebrogenic CLBP, but minimal data exists regarding BVN ablation's clinical effectiveness with broader application outside of strict trial inclusion criteria. Methods: Prospective, single arm, open label effectiveness trial of 48 patients from community spine and pain practices treated with BVN ablation. Inclusion criteria required more than 6 months of CLBP and type 1 or 2 Modic changes on MRI to be enrolled. Patients were followed post procedure for 12 months using ODI, VAS, EQ-5D-5L and SF-36 patient reported outcome metrics.Results: 47 patients successfully received BVN ablation and 45 patients completed 12 months of follow up. Mean reduction in ODI at 12 months was 32.31 +/- 14.07 (p<0.001) with 88.89% (40/45) patients reporting a ≥15 point ODI decrease at 12 months. Mean VAS pain score decrease was 4.31+/-2.51 at 12 months (p<0.001) and more than 69% reported a 50% reduction in VAS pain scale. Similarly, SF-36 and EQ-5D-5L scores improved 26.27+/-17.19 and 0.22+/-0.15 (each p<0.001). Conclusions: This data supports the clinical effectiveness of BVN ablation in the community practice setting, with similar 12 month improvements in patient reported outcomes as seen in previously published randomized control trials.

Extracorporeal shockwave therapy raises mechanical nociceptive threshold in horses with thoracolumbar pain.

BACKGROUND: Although extracorporeal shockwave therapy (ESWT) is a common treatment for horses with back pain, effects on mechanical nociceptive threshold (MNT) and multifidus muscle cross sectional area (CSA) in the spine are unknown. OBJECTIVES: To evaluate effects of ESWT on spinal MNT and multifidus muscle CSA in horses with thoracolumbar pain. STUDY DESIGN: Non-randomised trial. METHODS: Thoracolumbar spines of 12 horses with thoracolumbar pain were radiographed to document existing pathology. Each horse received three ESWT treatments, 2 weeks apart (days 0, 14, 28). Palpation scores were documented (days 0, 45 and 65). Ultrasonographic CSA of left and right multifidus muscles was recorded at T12, T14, T16, T18, L3 and L5 (days 0, 45 and 65). MNT was measured at the same spinal sites every 7 days (day 0-56). RESULTS: Mechanical nociceptive threshold in 10/12 horses (83%) was greater at each time point compared with day 0 (P < 0.05). Mechanical nociceptive threshold increased at all time points at six sites in 2/12 (16%), at five sites in 3/12 (25%), at four sites in 4/12 (33%) and at one site in 1/12 (8%; P < 0.05). Mechanical nociceptive threshold average per cent  increase from day 0 to 56 was 64% for the thoracic region (T12-T18) and 29% for the lumbar region (L3-L5). There was no statistical difference in MNT from day 35 to 56 (P = 0.25). A bimodal analgesic trend was observed following ESWT. Degree of radiographic change was not associated with response to treatment. No significant change in multifidus muscle CSA was observed. MAIN LIMITATIONS: Small study size and lack of control group. CONCLUSIONS: Three treatments of ESWT 2 weeks apart raised MNT over a 56-day period in horses with back pain, but did not influence change in CSA of the multifidus muscle. While ESWT appears justifiable for analgesia, physiotherapeutic techniques may be necessary in conjunction for concurrent muscle rehabilitation.

Immunogenicity of Potomac horse fever vaccine when simultaneously co-administered with rabies vaccine in a multivalent vaccine or as two monovalent vaccines at separate sites.

BACKGROUND: Potomac horse fever (PHF) is a potentially fatal enterocolitis of horses caused by Neorickettsia risticii. The disease was originally recognised almost 40 years ago in the state of Maryland in the US. It is now known to occur in many areas of North America, as well as having been described in South America and Europe. Monocomponent PHF vaccines are available, but clinical protection with vaccination has been reported to be inconsistent. OBJECTIVES: This study was designed to assess the immunogenicity of a commercially available Potomac Horse Fever (PHF) vaccine when administered as either a monovalent PHF vaccine simultaneously co-administered with a separate monovalent Rabies vaccine or as a multivalent PHF/Rabies vaccine in horses. STUDY DESIGN: Randomised parallel group trial. METHODS: Ninety-one client or University owned horses participated in this open-label randomised study, with 45 horses receiving the monovalent vaccines at separate sites and 46 receiving the multivalent vaccine at a single site. Serum PHF IFA titres were determined twice prior to vaccination and at 1, 2 and 3 months after vaccination. RESULTS: Both vaccination protocols exhibited poor immunogenicity, with only one-third of all the animals demonstrating seroconversion, defined as an increase in titre of greater than 400 over baseline, at any time point after vaccination. The monovalent PHF vaccine exhibited significantly greater immunogenicity in terms of the number of horses exhibiting seroconversion, as compared to the multivalent vaccine, at one (20 vs. 11, P = 0.03) and two (18 vs. 9, p = 0.02) months post vaccination. The monovalent PHF vaccine also exhibited significantly greater immunogenicity in terms of the median (interquartile range) IFA titres, as compared to the multivalent vaccine, at one (800 [200-1600] vs. 400 [200-800], P = 0.009) and 2 months (400 [200-1600] vs. 400 [100-800], P = 0.02) post vaccination. There was no significant difference between groups at 3 months in either seroconversion rate or median IFA titers. MAIN LIMITATIONS: This study did not assess the actual protective effects of PHF vaccination but rather used the serologic response to vaccination as a surrogate biomarker of immunity. CONCLUSIONS: The multivalent PHF/Rabies vaccine exhibited lower immunogenicity as compared to the monovalent PHF vaccine co-administered with a separate Rabies vaccine.

Nicotinamide Phosphoribosyltransferase Attenuates Methotrexate Response in Juvenile Idiopathic Arthritis and In Vitro.

Variability in response to methotrexate (MTX) in the treatment of juvenile idiopathic arthritis (JIA) remains unpredictable and poorly understood. Based on previous studies implicating an interaction between nicotinamide phosphoribosyltransferase (NAMPT) expression and MTX therapy in inflammatory arthritis, we hypothesized that increased NAMPT expression would be associated with reduced therapeutic response to MTX in patients with JIA. A significant association was found between increased plasma concentrations of NAMPT and reduced therapeutic response in patients with JIA treated with MTX. Inhibition of NAMPT in cell culture by either siRNA-based gene silencing or pharmacological inhibition with FK-866 was found to result in a fourfold increase in the pharmacological activity of MTX. Collectively, these findings provide evidence that NAMPT inhibits the pharmacological activity of MTX and may represent a predictive biomarker of response, as well as a therapeutic target, in the treatment of JIA with MTX.

Seroprevalence of Borrelia burgdorferi in Horses Presented for Coggins Testing in Southwest Virginia and Change in Positive Test Results Approximately 1 Year Later.

BACKGROUND: Lyme disease can affect people, dogs, and horses, but it remains poorly understood, especially in the horse. Determining the seroprevalence of Borrelia burgdorferi in horses in different geographic areas will enable better understanding of the epidemiology of the disease, thus improving diagnosis and treatment of affected animals. HYPOTHESIS: To determine the seroprevalence of B. burgdorferi in horses in southwest Virginia. ANIMALS: Horses presented for routine Coggins testing from January 2013 to January 2014 had additional blood drawn for Lyme Multiplex Assay testing. METHODS: Of 492 samples collected, 250 samples were analyzed using the Lyme Multiplex Assay. Of the 83 horses that had positive test results to at least 1 outer surface protein (Osp), 63 were available for follow-up testing 5-17 months later (June 2014). RESULTS: Thirty-three percent of horses had positive results for antibodies to at least 1 Osp. Horses with a positive outer surface protein F (OspF) result were older (14.5 ± 0.79) than horses with a negative OspF result (11.6 ± 0.53). Of the horses available for follow-up testing, 63% had the same result as that of the initial test. There was no difference in test result between initial and follow-up testing. CONCLUSIONS: Horses seropositive to B. burgdorferi are common in Virginia, and older horses are more likely to have a positive test result for OspF than younger horses. Follow-up testing indicated that the majority of horses that were positive on initial testing did not have a different test result 5-17 months later.

[Functional differences in the microcirculatory units of the eye]. / Funktionelle Unterschiede in den Mikrozirkulationsgebieten des Auges.

This review describes the most important regions of microcirculation within the eye - their architecture as well as their function. A special emphasis is put on the functional heterogeneity of the microvessels and their role regarding the specific functions localised within the different regions of the eye (e.g. oxygen release by the iris capillaries, production of aqueous humor within the ciliary processes). The microvasculature of choroidea and retina will be described in more detail. The precise adjustment of the blood flow to the functional needs of the inner retina is a very important aspect in the retinal vessels. Here, also pericytes can influence the vessel calibre like in the brain capillaries. Very important is the vascular reaction in general to states of hypoxia, especially to the hypoxic and radical producing states within the photoreceptors. The following reaction of neovascularisation will also be examined. Finally, we describe the metabolic situation of the ganglion cells and nerve fibers leading to and within the optic cup also with regard to glaucoma.

Human corneal endothelial cell sheets for transplantation: thermo-responsive cell culture carriers to meet cell-specific requirements.

Corneal endothelial diseases lead to severe vision impairment, motivating the transplantation of donor corneae or corneal endothelial lamellae, which is, however, impeded by endothelial cell loss during processing. Therefore, one prioritized aim in corneal tissue engineering is the generation of transplantable human corneal endothelial cell (HCEC) layers. Thermo-responsive cell culture carriers are widely used for non-enzymatic harvest of cell sheets. The current study presents a novel thermo-responsive carrier based on simultaneous electron beam immobilization and cross-linking of poly(vinyl methyl ether) (PVME) on polymeric surfaces, which allows one to adjust layer thickness, stiffness, switching amplitude and functionalization with bioactive molecules to meet cell type specific requirements. The efficacy of this approach for HCEC, which require elaborate cell culture conditions and are strongly adherent to the substratum, is demonstrated. The developed method may pave the way to tissue engineering of corneal endothelium and significantly improve therapeutic options.

Seasonal changes in the combined glucose-insulin tolerance test in normal aged horses.

BACKGROUND: Equine metabolic syndrome (EMS) is an increasingly recognized problem in adult horses. Affected horses are often obese and predisposed to the development of laminitis, especially in the spring and summer months. In addition, in the summer and fall months, increases in endogenous insulin concentrations, a marker of EMS, have been reported. HYPOTHESIS/OBJECTIVES: The purpose of this study was to evaluate seasonal changes in results of the combined glucose-insulin tolerance test (CGIT), a diagnostic test for EMS. ANIMALS: Nine healthy, aged horses with no history of laminitis and no clinical signs of EMS. METHODS: Horses were given dextrose (150 mg/kg) and insulin (0.1 U/kg) IV. Plasma glucose concentrations were measured at 0, 1, 5, 15, 30, 45, 60, 75, 90, and 150 minutes and serum insulin concentrations at 0, 5, and 75 minutes. Testing was performed in February, May, June, August, September, and November. Mean glucose concentrations, characteristics of the curve, and insulin concentrations during the CGIT were compared across months using repeated measures ANOVA (P < .05). RESULTS: No CGIT parameters indicated insulin resistance, but mean area under the curve for glucose concentrations was significantly lower in August and November compared to February and in November compared to June, indicating increased insulin-mediated glucose clearance. Glucose nadir was significantly lower in November compared to that in February. CONCLUSIONS AND CLINICAL IMPORTANCE: No clinically relevant differences were seen in the results of the CGIT, suggesting that season minimally affects results of this test in normal aged horses in the southeastern United States.

[Quality assurance in coding expertise of hospital cases in the German DRG system. Evaluation of inter-rater reliability in MDK expertise]. / Qualitätssicherung in der Kodierungsbegutachtung von Krankenhausfällen im G-DRG-System. Prüfung der Interrater-Reliabilität bei MDK-Gutachtern.

AIM: The purpose of this study was to evaluate differences in the D-DRG results of a hospital case by 2 independently coding MKD raters. Calculation of the 2-inter-rater reliability was performed by examination of the coding of individual hospital cases. The reasons for the non-agreement of the expert evaluations and suggestions to improve the process are discussed. METHODS: From the expert evaluation pool of the MDK-WL a random sample of 0.7% of the 57,375 expertises was taken. Distribution equality with the basic total was tested by the χ² test or, respectively, Fisher's exact test. For the total of 402 individual hospital cases, the G-DRG case sums of 2 experts of the MDK were determined independently and the results checked for each individual case for agreement or non-agreement. The corresponding confidence intervals with standard errors were analysed to test if certain major diagnosis categories (MDC) were statistically significantly more affected by differing expertise results than others. RESULTS: In 280 of the total 402 tested hospital cases, the 2 MDK raters independently reached the same G-DRG results; in 122 cases the G-DRG case sums determined by the 2 raters differed (agreement 70%; CI 65.2-74.1). Different DRG results between the 2 experts occurred regularly in the entire MDC spectrum. No MDC chapter in which significant differences between the 2 raters arose could be identified. CONCLUSION: The results of our study demonstrate an almost 70% agreement in the evaluation of hospital cost accounts by 2 independently operating MDK. This result leaves room for improvement. Optimisation potentials can be recognised on the basis of the results. Potential for improvement was established in combination with regular further training and the expansion of binding internal code recommendations as well as exchange of code-relevant information among experts in internal forums. The presented model is in principle suitable for cross-border examinations within the MDK system with the advantage that further trends could be uncovered by more variety and larger numbers of the randomly selected cases.

Healing quantitative trait loci in a combined cross analysis using related mouse strain crosses.

Inbred mouse strains MRL and LG share the ability to fully heal ear hole punches with the full range of appropriate tissues without scarring. They also share a common ancestry, MRL being formed from a multi-strain cross with two final backcrosses to LG before being inbred by brother-sister mating. Many gene-mapping studies for healing ability have been performed using these two strains, resulting in the location of about 20 quantitative trait loci (QTLs). Here, we combine two of these crosses (N = 638), MRL/lpr × C57BL/6NTac and LG/J × SM/J, in a single combined cross analysis to increase the mapping power, decrease QTL support intervals, separate multiple QTLs and establish allelic states at individual QTL. The combined cross analysis located 11 QTLs, 6 affecting only one cross (5 LG × SM and 1 MRL × B6) and 5 affecting both crosses, approximately the number of common QTLs expected given strain SNP similarity. Amongst the five QTLs mapped in both crosses, three had significantly different genetic effects, additive in one cross and over or underdominant in the other. It is possible that allelic states at these three loci are different in SM and B6 because they lead to differences in dominance interactions with the LG and MRL alleles. QTL support intervals are 40% smaller in the combined cross analysis than in either of the single crosses. Combined cross analysis was successful in enhancing the interpretation of earlier QTL results for these strains.

Seasonal changes in plasma adrenocorticotropic hormone and α-melanocyte-stimulating hormone in response to thyrotropin-releasing hormone in normal, aged horses.

BACKGROUND: Results of diagnostic tests for equine pituitary pars intermedia dysfunction (PPID), including endogenous ACTH concentration and the overnight dexamethasone suppression test (DST), are affected by season. New and potentially more sensitive diagnostic tests for equine PPID, such as thyrotropin-releasing hormone (TRH)-stimulated ACTH response, have been developed, but have had limited evaluation of seasonality. OBJECTIVE: Our purpose was to evaluate seasonal changes in plasma ACTH and alpha-melanocyte-stimulating hormone (α-MSH) responses to TRH administration. ANIMALS: Nine, healthy, aged horses with normal DST results. METHODS: Synthetic TRH (1 mg) was administered IV. Plasma ACTH and α-MSH concentrations were measured at 0, 5, 10, 15, 20, 25, 30, 45, 60, and 180 minutes. Testing was performed in February, July, August, September, October, and November. Mean TRH-stimulated ACTH and α-MSH concentrations were compared across months and time by repeated measures analysis of variance. Significance was set at the P < .05 level. RESULTS: Concentrations of ACTH and α-MSH significantly increased after TRH administration. Endogenous and TRH-stimulated ACTH and α-MSH concentrations were significantly different across months with higher concentrations in the summer and fall compared with February. CONCLUSIONS AND CLINICAL IMPORTANCE: Plasma ACTH and α-MSH responses to TRH administration experience seasonal variation, with TRH-stimulated ACTH and α-MSH concentrations increasing from summer through fall. These results support previous evidence of a seasonal influence on the equine pituitary-adrenal axis. More research is warranted with a larger number of horses to determine if seasonal reference ranges for TRH stimulation testing need to be defined.

DC microelectrode array for investigating the intracellular ion changes.

Microelectrode arrays (MEAs) are extensively being used to study the electrical properties of cells. Most of the MEAs use metal electrodes which are in direct contact with the cells. When using DC currents, this leads to undesirable chemical influencing of the cell. Also, metal electrodes are unsuitable for the measuring of constant potentials. A new kind of MEA is developed which replaces the metal electrodes by electrolyte-filled microchannels with Ag/AgCl-electrodes at their ends. The surface of the DCMEA consists of a nanoporous membrane that acts as a homogenous cell substrate, thus avoiding any topographical guidance of the cells. It is adhered to a polydimethylsiloxane layer with four electrode channels embedded in it, using a novel plasma bonding method. A transparent polymer ground plate connects the channels to the silver electrodes as shown in Fig. 1. This MEA allows for the stimulation of the cells with stationary, non-homogenous electric fields, e.g. to simulate the electrical environment near wounds in vitro. It has been proposed in the literature that intracellular ions are involved during cell migration. The DCMEA can be used to simulate in vitro electric fields to investigate intracellular ion changes. By loading cells with ion specific fluorescence dyes, real-time ion kinetic changes can directly be carried out on DCMEA. These studies will be performed by using a time lapse video microscope. In this paper we present the detailed fabrication and testing of the new DCMEA. Results on intracellular ion flows will be presented using this DCMEA.

Biological relevance of ion energy in performance of human endothelial cells on ion-implanted flexible polyurethane surfaces.

To improve the biocompatibility of polyurethane (PUR), we modified the surface by irradiation with different ions (Carbon; C, Oxygen; O, Nitrogen; N, or Argon; Ar) at 0.3-50 keV energy and doses of 1,00E+13 - 1,00E+15 ions/cm(2). The effects of ion implantation using different ion energies and densities were observed on adhesion, proliferation, and viability of human umbilical vein endothelial cells (HUVECs). The long-term in vitro stability of ion-implanted PUR was also investigated. Ion irradiation moderately affected the surface roughness (R(a)), but strongly enhanced the work of adhesion (W(a)). Cell adhesion was markedly improved on O-, N-, and Ar-, but not on C-implanted PUR surfaces. Medium ion energies and lower ion doses produced the best HUVEC attachment and proliferation, indicating the importance of choosing the proper range of energy applied during ion irradiation. In addition, apoptosis rates were significantly reduced when compared with unmodified PUR (uPUR). N implantation significantly protected the surface, although C implantation led to stronger surface erosions than on uPUR. In total, ion implantation on flexible PUR surfaces strongly improved the material surface characteristics and biocompatibility. Electron beam ion implantation within an appropriate energy window is thus a key to improving flexible PUR surfaces for clinical use to support endothelial cell performance. Thus, it can contribute to designing small-diameter grafts, which are in great demand, towards vascular tissue engineering applications.

[Cataract extraction and blue light--impact on the retina]. / Kataraktextraktion und Blaulicht--Wirkung auf die Netzhaut.

This review focuses on the scientific background for the use of "yellow artificial lenses". We will address the fact that numerous basic scientific publications point to a rationale for this practice although it is often difficult to derive clear-cut evidence from clinical epidemiological studies for the preventive use of yellow artificial lenses. In the first part we refer to studies showing that especially the shortwave part of the visible spectrum of light can be harmful for the retina and optic nerve. For this, we have screened the literature for the major sources of radical production and for the targets of oxidative stress after impingement of "blue light" on the retina. Furthermore, we can show that many studies in cell and molecular biology, animal experiments and first clinical trials point to a preferential use of yellow-tinted lenses especially in the elderly and AMD patients.

Physical vapor deposition of zirconium or titanium thin films on flexible polyurethane highly support adhesion and physiology of human endothelial cells.

The aim of this study was to develop and characterize novel metal-polymer constructs to improve the biocompatibility of flexible but hydrophobic polyurethane (PUR) implants. Using a physical vapor deposition (PVD) technique, thin films (< or =100 nm) of zirconium (Zr) or titanium (Ti) were deposited on the polyurethane surface. Both coatings displayed good stability when subjected to cross-cutting test and especially Zr showed only minor and superficial cracks in the scanning electron microscopy analysis. PVD coating resulted in significantly lowered contact angles and the standard surface free energy of wetting (Delta(wet)G degrees ) turned to more favorable negative values (Ti: -40; Zr: -30; untreated PUR (uPUR): +10.1 mN/m). This may lead to the highly enhanced adhesion and proliferation properties observed with human umbilical vein endothelial cells (HUVECs). In addition, the novel coatings had no toxic effect and even drastically reduced apoptosis rates of HUVECs. Cell morphology, nitric oxide production, and mitochondrial membrane potential--both at static and flow conditions--were superior compared with uPUR, thus demonstrating intact physiological functions. Therefore, we suggest that combining PUR as a flexible material with a thin coating of Zr or Ti as the improved biocompatible surface may have advantages for use, for example, vascular graft material.

Neurodegenerative diseases of the retina and potential for protection and recovery.

Recent advances in our understanding of the mechanisms in the cascade of events resulting in retinal cell death in ocular pathologies like glaucoma, diabetic retinopathy and age-related macular degeneration led to the common descriptive term of neurodegenerative diseases of the retina. The final common pathophysiologic pathway of these diseases includes a particular form of metabolic stress, resulting in an insufficient supply of nutrients to the respective target structures (optic nerve head, retina). During metabolic stress, glutamate is released initiating the death of neurones containing ionotropic glutamate (N-methyl-D-aspartat, NMDA) receptors present on ganglion cells and a specific type of amacrine cells. Experimental studies demonstrate that several drugs reduce or prevent the death of retinal neurones deficient of nutrients. These agents generally block NMDA receptors to prevent the action of glutamate or halt the subsequent pathophysiologic cycle resulting in cell death. The major causes for cell death following activation of NMDA receptors are the influx of calcium and sodium into cells, the generation of free radicals linked to the formation of advanced glycation endproducts (AGEs) and/or advanced lipoxidation endproducts (ALEs) as well as defects in the mitochondrial respiratory chain. Substances preventing these cytotoxic events are considered to be potentially neuroprotective.

Pam3CSK4 and LTA-TLRs ligands associated with microdomains induce IL8 production in human adrenocortical cancer cells.

Bacterially derived ligands, Pam3CSK4 and LPS, can directly impact adrenal glands steroidogenesis through microdomain-related TLR1/2 and 4, respectively, and indirectly via immune cell-derived cytokines. The bilateral immunoadrenal relationship plays an important role in the proper functioning of both systems. CXC chemokine-dependent immune cell infiltration into adrenocortical carcinomas (ACC), which correlates with poor prognosis, is a common phenomenon. Recently, IL8 was identified in ACC and NCI-H295R cells, and was found to contribute to ACC tumour growth. The aim of this study was to clarify the role of different TLR ligands in IL8 production in NCI-H295R cells. This is the first study to demonstrate the expression of several TLRs including TLR1, 3, 6, 7 and 9 in human adrenocortical cells by using the RT-PCR approach. Only stimulation with TLR1/6 together with TLR2 ligands resulted in IL8 peptide and mRNA induction in a dose and time-dependent manner. Our data suggest that gram-positive bacteria-related TLR1/2/6 ligands might contribute to adrenal gland tumorigenesis via IL8 production.

[DRG evaluation results--state comparisons: MDK Baden-Württemberg versus MDK Westfalen-Lippe]. / DRG-Prüfergebnisse im Ländervergleich: MDK Baden-Württemberg und MDK Westfalen-Lippe.

We report on the first detailed comparison of evaluation results regarding the correct billing in the G-DRG (German diagnosis-related group) system. For two Medical Review Boards of the Statutory Health Insurance Funds of comparable size (MDK Baden-Württemberg and MDK Westfalen-Lippe), we analysed consecutive expertises regarding correct billing according to section sign 275 SGB V, and the results were compared in terms of the frequency of DRG-relevant error codes, their relevance to revenue, and the question of error clustering (specific DRGs, primary diagnoses, etc.). The analysis comprised 51,010 individual expertises pertaining to billings of the year 2005 (admittance to hospital from January 1 to December 31, 2005). The proportion of disapproved cases was 38.5% in Baden-Württemberg and 44.6% in Westfalen-Lippe. Among these, errors to the disadvantage of the Health Insurance (incorrectly high) were 33.9% and 39.3%, respectively, and errors to the disadvantage of the hospitals (incorrectly low) were 4.6% and 5.3%, respectively. The resulting ratio (incorrectly high vs. low) was an identical 7.4 in both cases. Not only the most commonly rejected DRGs but also the primary and secondary diagnoses were similar in both cases, while the disapproved procedure codes showed a significant variability (analysis based on the respective 10 most common objections). We discuss the similarities and differences in these results and their possible causes, and demonstrate the cost relevance of this audit segment. Result comparisons of this type can yield insights into streamlining of the review practice of Medical Review Boards, as well as increase the efficiency and effectiveness of the selection of cases.

Vascular-adrenal niche--endothelial cell-mediated sensitization of human adrenocortical cells to angiotensin II.

Alterations in both vasculature and renin-angiotensin-aldosterone system are a consistent finding in the metabolic syndrome. Adrenal tissue is highly vascularized and encounters blood flow, exceeding by far the volume expected for its size. Endothelial cells in the adrenal vasculature are therefore a major cellular component of adrenocortical tissue. The aim of the study was to analyze the cellular interaction between endothelial and steroid producing cells, focusing on endothelial cell-factor-mediated activation of aldosterone synthesis. The interaction between human endothelial (HUVECs) cell-conditioned medium and human adrenocortical (NCI-H295R) cells IN VITRO induced a significant surge in aldosterone secretion. The endothelial cell-conditioned medium together with angiotensin II and forskolin also potentiated aldosterone release by 1.5-fold and 2.6-fold, respectively, while preincubation of NCI-H295R cells for 24 h with endothelial cell-conditioned medium enhanced and sensitized the response of NCI-H295R to subsequent angiotensin II and forskolin stimuli by 2.5-fold and 2.2-fold, respectively. The increase in aldosterone release after preincubation with endothelial cell-conditioned medium was sensitive to cycloheximide and KN-93. Cellular conditioning with endothelial-cell factors exerts a hitherto unknown paracrine regulation of aldosterone production in human adrenocortical cells. This interaction may contribute to altered basal aldosterone release and have a role in patients with hypertension.

Effects of different titanium alloys and nanosize surface patterning on adhesion, differentiation, and orientation of osteoblast-like cells.

To test nanosize surface patterning for application as implant material, a suitable titanium composition has to be found first. Therefore we investigated the effect of surface chemistry on attachment and differentiation of osteoblast-like cells on pure titanium prepared by pulsed laser deposition (TiPLD) and different Ti alloys (Ti6Al4V, TiNb30 and TiNb13Zr13). Early attachment (30 min) and alkaline phosphatase (ALP) activity (day 5) was found to be fastest and highest, respectively, in cells grown on TiPLD and Ti6Al4V. Osteoblasts seeded on TiPLD produced most osteopontin (day 10), whereas expression of this extracellular matrix protein was an order of magnitude lower on the TiNb30 surface. In contrast, expression of the corresponding receptor, CD44, was not influenced by surface chemistry. Thus, TiPLD was used for further experiments to explore the influence of surface nanostructures on osteoblast adhesion, differentiation and orientation. By laser-induced oxidation, we produced patterns of parallel Ti oxide lines with different widths (0.2-10 microm) and distances (2-20 and 1,000 microm), but a common height of only 12 nm. These structures did not influence ALP activity (days 5-9), but had a positive effect on cell alignment. Two days after plating, the majority of the focal contacts were placed on the oxide lines. The portion of larger focal adhesions bridging two lines was inversely related to the line distance (2-20 microm). In contrast, the portion of aligned cells did not depend on the line distance. On average, 43% of the cells orientated parallel towards the lines, whereas 34% orientated vertically. In the control pattern (1,000 microm line distance), cell distribution was completely at random. Because a significant surplus of the cells preferred a parallel alignment, the nanosize difference in height between Ti surface and oxide lines may be sufficient to orientate the cells by contact guiding. However, gradients in electrostatic potential and surface charge density at the Ti/Ti oxide interface may additionally influence focal contact formation and cell guidance.