Femoral head injuries: Which treatment strategy can be recommended?

Despite different operative and non-operative treatment regimens, the outcome after femoral head fractures has changed little over the past decades. The initial trauma itself as well as secondary changes such as posttraumatic osteoarthritis, avascular necrosis or heterotopic ossification is often responsible for severe loss of function of the afflicted hip joint. Anatomic reduction of all fracture fragments seems to be a major influencing factor in determining the outcome quality. Eight years ago we inaugurated a new surgical approach for better access and visualisation for the treatment of femoral head fractures, using the "trochanteric flip" (digastric) osteotomy. Thus inspection of the entire hip joint and accurate fragment reduction under direct visual control are possible. After good initial experiences with this operative procedure we changed our standard treatment regimen to this approach in an attempt to achieve the most accurate anatomic reduction of the femoral head in every affected patient. Between 1998 and 2006 we operated on 12 patients with femoral head fractures associated with posterior hip dislocation, using the new surgical approach. Patients were followed for 2-96 months and outcome was documented with the Merle d'Aubigne and Postel score as well as the Thompson and Epstein score. The posttraumatic formation of heterotopic bone was documented with the Brooker score. Retrospective analysis of these 12 patients showed good or excellent results in 10 patients (83.3%). The two patients with poor outcome developed an avascular necrosis of the femoral head and underwent total hip arthroplasty. Periarticular heterotopic ossification was seen in five patients. In four patients this caused a significantly reduced range of motion and was therefore considered as a posttraumatic complication. The two patients with the most severe heterotopic bone formation (Brooker III and IV) had initially sustained multiple injuries including brain injury. Comparing our results with earlier published series including our own before changing the treatment protocol, the data suggest a favorable outcome in patients with trochanteric flip (digastric) osteotomy for the treatment of femoral head fractures.

Cardiovascular risk factors impair native collateral development and may impair efficacy of therapeutic interventions

Animal and early clinical studies of gene therapy for tissue ischaemia suggested that this approach might provide benefit to patients with coronary artery disease not amenable to traditional revascularization. This enthusiasm was then tempered by the subsequent disappointing results of randomized clinical trials and led researchers to develop strategies using progenitor cells as an alternative to improve collateral function. However, the recent publication of several randomized clinical trials reporting either negative or weakly positive results using this approach have led to questions regarding its effectiveness. There are several factors that need to be considered in explaining the discordance between the positive studies of such treatments in animals and the disappointing results seen in randomized patient trials. Aside from the practical issues of arteriogenic therapies, such as effective delivery, vascular remodelling is an extraordinarily complex process, and the administration of a single agent or cell in the hope that it would lead to lasting physiological effects may be far too simplistic an approach. In addition, however, evidence now suggests that many of the traditional cardiovascular risk factors-such as age and hypercholesterolemia-may impair the host response not only to ischaemia but, critically, also to treatment as well. This review discusses the evidence and mechanisms for these observations and highlights future directions that might be taken in an effort to provide more effective therapies.

Severe phenotype with cis-acting heterozygous PMP22 mutations

We report on a 20-year-old male with severe Charcot-Marie-Tooth (CMT) disease and a de novo deletion (c.281delG, p.G94AfsX17) on the paternal PMP22 allele harboring c.353C>T (p.T118M). RNA-based sequence analysis confirmed the absence of nonsense-mediated decay and the presence of the mutant transcripts in Epstein-Barr virus-transformed lymphoblastoid cells of our patient. His clinical findings included early onset of polyneuropathy, loss of muscle mass with distal pareses, hammer toes, and progressive scoliosis. There was no neuropsychological alteration. Our results suggest that the deletion c.281delG alone is responsible for the severe CMT phenotype. To the best of our knowledge, this is the second report on a proven paternal origin of a de novo single-base mutation in the PMP22 gene.

Orbitale Fettgewebsatrophie bei lokaler Bimatoprost-Therapie - Kann Bimatoprost einen Enophthalmus verursachen?

PURPOSE: The aim of this communication is to report enophthalmos as a possible new adverse effect of topical bimatoprost treatment. PATIENTS AND METHODS: A retrospective case series of five glaucoma patients under long-term topical bimatoprost treatment was evaluated. Documentation with photo and Hertel exophthalmometry was reviewed. RESULTS: In all five patients a deep lid sulcus, reduced infraocular fat pads and enophthalmos-suspicious Hertel values were found (mean 11.9 mm; SD 2.4). Other aetiologies for enophthalmos were excluded anamnestically and by clinical examination. CONCLUSION: Bimatoprost may lead to an alteration of the eyelid with deepening of the lid sulcus and may also be responsible for an iatrogenic orbital fat atrophy. A possible mechanism of action might be the induction of apoptosis of orbital fibroblasts with a remodelling of the extracellular matrix. Prospective studies are necessary to confirm this cross-sectional observation.

Arctic patterned-ground ecosystems: A synthesis of field studies and models along a North American Arctic Transect

Arctic landscapes have visually striking patterns of small polygons, circles, and hummocks. The linkages between the geophysical and biological components of these systems and their responses to climate changes are not well understood. The "Biocomplexity of Patterned Ground Ecosystems" project examined patterned-ground features (PGFs) in all five Arctic bioclimate subzones along an 1800-km trans-Arctic temperature gradient in northern Alaska and northwestern Canada. This paper provides an overview of the transect to illustrate the trends in climate, PGFs, vegetation, n-factors, soils, active-layer depth, and frost heave along the climate gradient. We emphasize the thermal effects of the vegetation and snow on the heat and water fluxes within patterned-ground systems. Four new modeling approaches build on the theme that vegetation controls microscale soil temperature differences between the centers and margins of the PGFs, and these in turn drive the movement of water, affect the formation of aggradation ice, promote differential soil heave, and regulate a host of system propel-ties that affect the ability of plants to colonize the centers of these features. We conclude with an examination of the possible effects of a climate wan-ning on patterned-ground ecosystems.

Coronary artery injury due to catheter ablation in adults: presentations and outcomes

BACKGROUND: Currently, only anecdotal information exists on the presentation and outcome of coronary arterial injury after ablation procedures. METHODS AND RESULTS: Four patients who sustained coronary artery injury of a cohort of patients undergoing 4655 consecutive ablation procedures (0.09%) are described. The patients' mean age was 45+/-11 years, and 1.8+/-0.5 prior ablation attempts had been unsuccessful. Coronary injury occurred from epicardial ventricular tachycardia ablation in 2 patients (irrigated radiofrequency ablation in one and cryoablation in the other) and ablation within the middle cardiac vein with irrigated radiofrequency in 2 patients. All involved branches of the right coronary artery. Acute occlusion presenting with ST-segment elevation immediately after ablation was recognized during the procedure in 2 cases. Occlusion failed to respond to nitroglycerin or balloon dilation, and stenting was required in both cases. Acute myocardial infarction occurred 2 weeks after epicardial ablation as a result of occlusion of a right ventricular branch of the right coronary artery giving rise to the posterior descending coronary artery in 1 patient. A moderate asymptomatic stenosis was seen on angiography after epicardial cryoablation in 1 patient. All patients recovered and remained asymptomatic from the coronary injury and arrhythmias during 37+/-53 months of follow-up. CONCLUSIONS: Coronary arterial injury after ablation procedures is rare. It may present acutely or several weeks after an ablation procedure. Acute occlusion appears to require coronary stenting. Unanticipated anatomic variations can predispose to coronary injury.

Gene therapy for immunodeficiency due to adenosine deaminase deficiency

BACKGROUND: We investigated the long-term outcome of gene therapy for severe combined immunodeficiency (SCID) due to the lack of adenosine deaminase (ADA), a fatal disorder of purine metabolism and immunodeficiency. METHODS: We infused autologous CD34+ bone marrow cells transduced with a retroviral vector containing the ADA gene into 10 children with SCID due to ADA deficiency who lacked an HLA-identical sibling donor, after nonmyeloablative conditioning with busulfan. Enzyme-replacement therapy was not given after infusion of the cells. RESULTS: All patients are alive after a median follow-up of 4.0 years (range, 1.8 to 8.0). Transduced hematopoietic stem cells have stably engrafted and differentiated into myeloid cells containing ADA (mean range at 1 year in bone marrow lineages, 3.5 to 8.9%) and lymphoid cells (mean range in peripheral blood, 52.4 to 88.0%). Eight patients do not require enzyme-replacement therapy, their blood cells continue to express ADA, and they have no signs of defective detoxification of purine metabolites. Nine patients had immune reconstitution with increases in T-cell counts (median count at 3 years, 1.07x10(9) per liter) and normalization of T-cell function. In the five patients in whom intravenous immune globulin replacement was discontinued, antigen-specific antibody responses were elicited after exposure to vaccines or viral antigens. Effective protection against infections and improvement in physical development made a normal lifestyle possible. Serious adverse events included prolonged neutropenia (in two patients), hypertension (in one), central-venous-catheter-related infections (in two), Epstein-Barr virus reactivation (in one), and autoimmune hepatitis (in one). CONCLUSIONS: Gene therapy, combined with reduced-intensity conditioning, is a safe and effective treatment for SCID in patients with ADA deficiency. (ClinicalTrials.gov numbers, NCT00598481 and NCT00599781.)

A comparative assessment of endothelium from pseudophakic and phakic donor corneas stored in organ culture

AIMS To evaluate the endothelial quality of corneas obtained from pseudophakic donors and to compare the data with matched phakic controls. METHODS Corneas from eyes with posterior chamber intraocular lenses (PCIOLs) and corneas from phakic eyes (controls) were stored for 1-2 weeks in organ culture and then examined after staining with Alizarin red S. The corneas were divided into two groups according to the duration of storage. Endothelial cell density, the percentage of hexagonal cells, and the coefficient of variation (CV) were determined. RESULTS There was no statistically significant difference between the 14 PCIOL corneas and the 13 controls stored in organ culture for 7 days for any of the three parameters studied. The mean cell density was 2155 (SD 529) cells/mm(2) in the PCIOL corneas and 2118 (453) cells/mm(2) in the controls (p=0.85). The mean percentage of hexagonal cells was 52% (8%) and 58% (7%), respectively (p=0.06). The mean CV was 0.32 (0.18) in the pseudophakic corneas and 0.39 (0.18) in the controls (p=0.33). Moreover, there was no significant difference between the PCIOL corneas and the controls stored for up to 2 weeks. CONCLUSIONS The corneal endothelium from eyes with PCIOLs appears to be similar to that of phakic eyes after 1-2 weeks in organ culture. This finding suggests that corneas from pseudophakic eyes should not routinely be disqualified for transplantation. The use of at least some pseudophakic corneas may substantially increase the potential donor pool.

Spatial and temporal patterns of greenness on the Yamal Peninsula, Russia: interactions of ecological and social factors affecting the Arctic normalized difference vegetation index

The causes of a greening trend detected in the Arctic using the normalized difference vegetation index (NDVI) are still poorly understood. Changes in NDVI are a result of multiple ecological and social factors that affect tundra net primary productivity. Here we use a 25 year time series of AVHRR-derived NDVI data (AVHRR: advanced very high resolution radiometer), climate analysis, a global geographic information database and ground-based studies to examine the spatial and temporal patterns of vegetation greenness on the Yamal Peninsula, Russia. We assess the effects of climate change, gas-field development, reindeer grazing and permafrost degradation. In contrast to the case for Arctic North America, there has not been a significant trend in summer temperature or NDVI, and much of the pattern of NDVI in this region is due to disturbances. There has been a 37% change in early-summer coastal sea-ice concentration, a 4% increase in summer land temperatures and a 7% change in the average time-integrated NDVI over the length of the satellite observations. Gas-field infrastructure is not currently extensive enough to affect regional NDVI patterns. The effect of reindeer is difficult to quantitatively assess because of the lack of control areas where reindeer are excluded. Many of the greenest landscapes on the Yamal are associated with landslides and drainage networks that have resulted from ongoing rapid permafrost degradation. A warming climate and enhanced winter snow are likely to exacerbate positive feedbacks between climate and permafrost thawing. We present a diagram that summarizes the social and ecological factors that influence Arctic NDVI. The NDVI should be viewed as a powerful monitoring tool that integrates the cumulative effect of a multitude of factors affecting Arctic land-cover change.

Revealing the elusive molecular biology of the vault RNA

Recently several novel and previously reported non-protein-coding RNAs (ncRNAs) have been identified to be upregulated upon Epstein-Barr virus (EBV) infection in human B-lymphocytes. A group of these significantly upregulated ncRNAs are called vault RNAs (vtRNAs). ,b Only about 5% of the total cellular vtRNAs are connected to the vault particle, the largest known ribonucleoprotein particle (RNP) in eukaryotic cells. However the function of this ncRNA family and moreover of the vault particle remains still rather unclear. Our previous findings suggest a link between EBV infection and vtRNA expression. Consequently we are interested which part of the viral genome is responsible for the upregulation and moreover which function the vtRNAs might possess during virus propagation. To address this question we have separately overexpressed specific EBV-encoded, latently expressed proteins in BL2-cells to determine the influence on the vault RNA levels. Thereby we identified one EBV-encoded protein, called Latent Membrane Protein 1 (LMP1), which significantly contributes to the vtRNA upregulation. We used LMP1 mutants to characterize the region of the protein and the responsible pathway for triggering the elevated vtRNA expression. Our results suggest that the NFkB- pathway might be involved in this process. To investigate a possible functional connection between the vtRNA and EBV infection, we have overexpressed vtRNA1-1 in BL41, a cell line usually not expressing this vault RNA. We show that overexpression of vtRNA1-1 leads to a better viral establishment and markedly protects cells from undergoing apoptosis. Knock-down of the major vault protein, the main component of the vault particle, had no effect on EBV infection and apoptosis resistance. Thus these results support the view that the observed phenotype is caused by the vtRNA rather than the vault particle.

Corneal cross-linking in keratoconus using the standard and rapid treatment protocol: differences in demarcation line and 12-month outcomes.

PURPOSE To compare the occurrence rate and depth of the demarcation line and topographical outcome after corneal cross-linking (CXL) for keratoconus using two different treatment protocols. METHODS A retrospective analysis of 131 eyes with progressive keratoconus treated with CXL using riboflavin and UV-A was performed. Eyes were treated either with the standard Dresden protocol (30 minutes irradiation, 3 mW/cm(2), UV-XTM 1000) or a rapid protocol (10 minutes irradiation, 9 mW/cm(2), UV-XTM 2000). The presence and depth of the corneal demarcation line was assessed with an anterior segment optical coherence tomography device 1 month after CXL by a masked observer. Corneal topography and tomography was performed at baseline and at 12-month follow-up with Pentacam and the TMS (Topographic Modeling System) device. RESULTS In the standard protocol group, 76.5% (62/81) of treated corneas revealed a demarcation line 1 month after CXL, whereas such a demarcation line was observed in only 22% (11/50) of eyes treated with the rapid protocol (P < 0.0001). The demarcation line was significantly more superficial in the rapid protocol group (P = 0.004). Corneal topography values between baseline and 12 months after CXL showed a mean change of -0.76 diopters (D) in Kmax (SD ± 2.7) in the standard protocol group versus a mean change of +0.72 D in Kmax (SD ± 1.5) in the rapid protocol (P = 0.007). CONCLUSIONS The rapid CXL protocol negatively influences the occurrence and depth of the demarcation line 1 month after CXL. Our results show a negative effect on the topographical outcome 1 year after CXL.

Impact of corneal cross-linking on topical drug penetration in humans.

PURPOSE To analyse the influence of corneal cross-linking (CXL) with ultraviolet-A (UV-A) and riboflavin on drug permeability in human subjects. METHODS Keratoconus patients (n = 23; mean age 26.9 ± 5.8 years) undergoing a standard CXL procedure with UV-A (5.4 J/cm(2) , 30 min) and riboflavin in one eye were included in the study. The pupillary diameter, measured before and every 3 min for 30 min after the topical application of one drop of 2% pilocarpine, was used as an indirect measure of the corneal permeability. The pupillary diameter was measured with an infrared pupillometer device before (baseline) and 4 months after CXL. RESULTS Prior to pilocarpine application, no significant difference in the pupillary diameter was detected before CXL and 4 months later. The mean decrease in the pupillary diameter after the application of pilocarpine was similar at baseline and the 4-month follow-up visit: mean decreases of 3.9 and 3.7 mm were observed 30 min after pilocarpine application, respectively (p > 0.05). CONCLUSIONS No significant influence of CXL on the corneal penetration of topically applied pilocarpine was observed in this clinical study.

Expression of the vault RNA protects cells from undergoing apoptosis

Non-protein-coding RNAs are a functionally versatile class of transcripts found in all domains of life exerting their biological role at the RNA level. Recently, we demonstrated that the vault-associated RNAs (vtRNAs) were significantly up-regulated in human B cells upon Epstein-Barr virus (EBV) infection [1,2]. vtRNAs are an integral part of the vault complex, a huge and evolutionarily conserved cytoplasmic ribonucleoprotein complex. The major vault protein (MVP) is the main structural component of the complex while vtRNA accounts for only 5% of its mass. Very little is known about the function(s) of the vtRNAs or the vault complex. In particular the role and significance of the previously observed vtRNA up-regulation upon EBV infection remained unclear. We individually expressed EBV-encoded genes in B cells and found the latent membrane protein 1 (LMP1) as trigger for vtRNA up-regulation. To unravel a putative functional interconnection between vtRNA expression and EBV infection, we ectopically expressed vtRNA1-1 in human B cells and observed an improved viral establishment. Furthermore, expression of vtRNA1-1 but not of the other vtRNA paralogs protected cells from undergoing apoptosis. Knock-down of MVP had no effect on these phenotypes thus revealing the vtRNA and not the vault complex to contribute to the enhanced EBV establishment and apoptosis resistance. Mutational analysis highlighted the central domain of the vtRNA to be involved in the anti-apoptotic effect. Ongoing research aims at characterizing the target of vtRNA1-1 in the apoptotic pathway. In summary, our data reveal a crucial cellular function for the so far elusive RNA biology of the vtRNAs.