De novo and inherited mutations in the X-linked gene CLCN4 are associated with syndromic intellectual disability and behavior and seizure disorders in males and females.

Variants in CLCN4, which encodes the chloride/hydrogen ion exchanger CIC-4 prominently expressed in brain, were recently described to cause X-linked intellectual disability and epilepsy. We present detailed phenotypic information on 52 individuals from 16 families with CLCN4-related disorder: 5 affected females and 2 affected males with a de novo variant in CLCN4 (6 individuals previously unreported) and 27 affected males, 3 affected females and 15 asymptomatic female carriers from 9 families with inherited CLCN4 variants (4 families previously unreported). Intellectual disability ranged from borderline to profound. Behavioral and psychiatric disorders were common in both child- and adulthood, and included autistic features, mood disorders, obsessive-compulsive behaviors and hetero- and autoaggression. Epilepsy was common, with severity ranging from epileptic encephalopathy to well-controlled seizures. Several affected individuals showed white matter changes on cerebral neuroimaging and progressive neurological symptoms, including movement disorders and spasticity. Heterozygous females can be as severely affected as males. The variability of symptoms in females is not correlated with the X inactivation pattern studied in their blood. The mutation spectrum includes frameshift, missense and splice site variants and one single-exon deletion. All missense variants were predicted to affect CLCN4's function based on in silico tools and either segregated with the phenotype in the family or were de novo. Pathogenicity of all previously unreported missense variants was further supported by electrophysiological studies in Xenopus laevis oocytes. We compare CLCN4-related disorder with conditions related to dysfunction of other members of the CLC family.

[Injuries of the posterior and lateral chest wall-importance of an additional clavicular fracture]. / Verletzungen der posterioren und lateralen Brustwand ­ Bedeutung einer zusätzlichen Klavikulafraktur.

BACKGROUND: Flail chest wall injuries (FCI) are common in younger patients due to high-speed trauma and in older patients due to low-energy trauma or falls from a low height. They show a high incidence of concomitant injuries and are therefore associated with high morbidity and mortality. If there is also an ipsilateral clavicular fracture (CF), the outcome is significantly poorer. The skeleton of the shoulder and chest loses stability and can lead to a loss of function of the shoulder and a pronounced deformation of the chest wall. OBJECTIVE: This article shows the origin and clinical importance of FCI. What importance does a concomitant ipsilateral CF have and how can these costoclavicular injuries (CCI) be managed conservatively and operatively? MATERIAL AND METHODS: After primary emergency care of the patients with appropriate diagnostics, in the presence of CCI operative stabilization was carried out by means of locked plate osteosynthesis of the clavicle and the affected ribs via minimally invasive approaches with the patient under general anesthesia. Patients were followed up postoperatively. Various minimally invasive posterolateral approaches to the chest wall were previously performed in a corpse study and then put into practice. RESULTS AND CONCLUSION: This study presents therapeutic options for the reconstruction of the chest wall based on the established literature and clinical examples. An ipsilateral CF combined with fractures of the 2nd-4th ribs can be treated through an innovative clavipectoral approach. For the other fractures, standard approaches to the anterolateral and posterolateral chest wall are performed, which are associated with a good outcome in clinical practice. An operative stabilization should be performed at the latest when FCI or CCI together with a dislocating fracture and a marked deformation of the thoracic wall are present. Remaining misalignments are associated with a simultaneous loss of function of the chest wall and shoulder.

[Lesions of the anterior chest wall-significance of additional fractures of the spine]. / Verletzungen der anterioren Brustwand ­ Bedeutung zusätzlicher Frakturen der Wirbelsäule.

BACKGROUND: Fractures of the anterior chest wall are rare among the total number of fractures. They include sternal fractures (SF) and the adjacent cartilaginous structures of the ribs. The accident mechanism can allow conclusions to be drawn about which further accompanying injuries may be present, e.g. rib and spinal fractures. OBJECTIVE: The present work is intended to give an overview of injuries of the anterior chest wall. It includes clinical aspects as well as imaging and popular literature. MATERIAL AND METHODS: Included are injury constellations of the anterolateral chest wall, in particular of the sternum in combination with injuries of the spinal column in the sense of a sternovertebral injury (SVI). Possible treatment strategies were reviewed and the corresponding advantages and disadvantages are presented. RESULTS: In symptomatic fractures of the anterior chest wall, their operative stabilization should be considered in order to restore the stability of the trunk. In addition, rib fractures in direct trauma and spinal injuries in indirect trauma are often included in the treatment. CONCLUSION: In the case of injuries of the thoracic trunk, this must always be regarded as a unit and must therefore be clarified in the context of the clinical examination and diagnostic apparatus. The possible accident mechanism can allow conclusions to be drawn about possible injury patterns, e.g. in the sense of SVIs.

[Frequency and age distribution of combined sternovertebral injuries : Analysis of routine data from German hospitals 2005-2012]. / Häufigkeit und Altersverteilung sternovertebraler Kombinationsverletzungen : Analyse aus Routinedaten deutscher Krankenhäuser 2005­2012.

BACKGROUND: Combinations of sternal and spinal fractures often occur due to high velocity accidents and are associated with a high incidence of concomitant injuries. The anterior thoracic wall is described as the fourth column of torso stability, which is why sternovertebral injuries (SVI) present a high risk of sagittal deformation of the trunk, in particular injuries of the thoracic spine. To date, no studies have been published on the frequency distribution of the involved vertebral bodies in large patient groups. OBJECTIVES: This study was intended to elaborate a frequency distribution of vertebral fractures accompanying sternal fractures (SF) and examine the risk of a vertebral fracture accompanying a SF. MATERIAL AND METHODS: A total of 48,193 cases with the main or secondary diagnosis of a SF and 897,963 cases with vertebral fractures based on routine data of German hospitals from the years 2005-2012 were evaluated. A concomitant injury to the spinal column was examined for each vertebral body and then evaluated statistically. RESULTS AND CONCLUSIONS: Of all patients with a SF 30.96% also suffered from a vertebral fracture. Of these 3.11% were SF as the main diagnosis and 60.89% the secondary diagnosis. While vertebral fractures generally occurred most frequently in the region of the thoracolumbar transition and the second cervical vertebral body, the SVI showed a further frequency peak in the range from the lower cervical spine to the middle thoracic spine. The present study was able to show a frequency distribution of accompanying vertebral body injuries in a large and representative collective in the case of SF for the first time.

Limited evidence of chondrocyte outgrowth from adult human articular cartilage.

OBJECTIVE: Cellular outgrowth from articular cartilage tissue has been described in a number of recent experimental studies. The aim of this study was to investigate the occurrence of cellular outgrowth from articular cartilage explants isolated from adult human donors. METHOD: Macroscopically intact articular cartilage specimens were isolated from adult human donors and cultured either in their native status, or in a cleansed status achieved by forced washing to minimize attaching cells. Additionally, the effect of chemotactic stimuli including cell lysate, High-Mobility-Group-Protein B1 (HMGB-1), Trefoil-factor 3 (TFF3), bone morphogenetic protein-2 (BMP-2), transforming growth factor-ß1 (TGF-ß1), or three-dimensional fibrin or collagen matrices were investigated. Co-cultures with synovial membrane served as a positive control for a source of migratory cells. The occurrence of cellular outgrowth was analyzed by histological examination after a culture period of 4 weeks. RESULTS: Spontaneous cellular outgrowth from cleansed cartilage specimens was not observed at a relevant level and could not significantly be induced by chemotactic stimuli or three-dimensional matrices either. A forming cartilage-adjoining cell layer was only apparent in the case of native cartilage explants with cellular remnants from surgical isolation or in co-culture experiments with synovial membrane. CONCLUSION: The relevance of cellular outgrowth from cartilage tissue is largely absent in the case of adult human articular cartilage samples. A cartilage-adjoining cell layer forming around the explants may instead originate from still attaching cells that remained from surgical isolation.

Functional ankle instability as a risk factor for osteoarthritis: using T2-mapping to analyze early cartilage degeneration in the ankle joint of young athletes.

OBJECTIVE: The aim of this study was to investigate, using T2-mapping, the impact of functional instability in the ankle joint on the development of early cartilage damage. METHODS: Ethical approval for this study was provided. Thirty-six volunteers from the university sports program were divided into three groups according to their ankle status: functional ankle instability (FAI, initial ankle sprain with residual instability); ankle sprain Copers (initial sprain, without residual instability); and controls (without a history of ankle injuries). Quantitative T2-mapping magnetic resonance imaging (MRI) was performed at the beginning ('early-unloading') and at the end ('late-unloading') of the MR-examination, with a mean time span of 27 min. Zonal region-of-interest T2-mapping was performed on the talar and tibial cartilage in the deep and superficial layers. The inter-group comparisons of T2-values were analyzed using paired and unpaired t-tests. Statistical analysis of variance was performed. RESULTS: T2-values showed significant to highly significant differences in 11 of 12 regions throughout the groups. In early-unloading, the FAI-group showed a significant increase in quantitative T2-values in the medial, talar regions (P = 0.008, P = 0.027), whereas the Coper-group showed this enhancement in the central-lateral regions (P = 0.05). Especially the comparison of early-loading to late-unloading values revealed significantly decreasing T2-values over time laterally and significantly increasing T2-values medially in the FAI-group, which were not present in the Coper- or control-group. CONCLUSION: Functional instability causes unbalanced loading in the ankle joint, resulting in cartilage alterations as assessed by quantitative T2-mapping. This approach can visualize and localize early cartilage abnormalities, possibly enabling specific treatment options to prevent osteoarthritis in young athletes.

Molecular differentiation between osteophytic and articular cartilage--clues for a transient and permanent chondrocyte phenotype.

OBJECTIVE: To identify the molecular differences between the transient and permanent chondrocyte phenotype in osteophytic and articular cartilage. METHODS: Total RNA was isolated from the cartilaginous layer of osteophytes and from intact articular cartilage from knee joints of 15 adult human donors and subjected to cDNA microarray analysis. The differential expression of relevant genes between these two cartilaginous tissues was additionally validated by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and by immunohistochemistry. RESULTS: Among 47,000 screened transcripts, 600 transcripts were differentially expressed between osteophytic and articular chondrocytes. Osteophytic chondrocytes were characterized by increased expression of genes involved in the endochondral ossification process [bone gamma-carboxyglutamate protein/osteocalcin (BGLAP), bone morphogenetic protein-8B (BMP8B), collagen type I, alpha 2 (COL1A2), sclerostin (SOST), growth arrest and DNA damage-induced gene 45ß (GADD45ß), runt-related transcription factor 2 (RUNX2)], and genes encoding tissue remodeling enzymes [matrix metallopeptidase (MMP)9, 13, hyaluronan synthase 1 (HAS1)]. Articular chondrocytes expressed increased transcript levels of antagonists and inhibitors of the BMP- and Wnt-signaling pathways [Gremlin-1 (GREM1), frizzled-related protein (FRZB), WNT1 inducible signaling pathway protein-3 (WISP3)], as well as factors that inhibit terminal chondrocyte differentiation and endochondral bone formation [parathyroid hormone-like hormone (PTHLH), sex-determining region Y-box 9 (SOX9), stanniocalcin-2 (STC2), S100 calcium binding protein A1 (S100A1), S100 calcium binding protein B (S100B)]. Immunohistochemistry of tissue sections for GREM1 and BGLAP, the two most prominent differentially expressed genes, confirmed selective detection of GREM1 in articular chondrocytes and that of BGLAP in osteophytic chondrocytes and bone. CONCLUSIONS: Osteophytic and articular chondrocytes significantly differ in their gene expression pattern. In articular cartilage, a prominent expression of antagonists inhibiting the BMP- and Wnt-pathway may serve to lock and stabilize the permanent chondrocyte phenotype and thus prevent their terminal differentiation. In contrast, osteophytic chondrocytes express genes with roles in the endochondral ossification process, which may account for their transient phenotype.

Injury risk evaluation in sport climbing.

The aim of this study was to quantify and rate acute sport climbing injuries. Acute sport climbing injuries occurring from 2002 to 2006 were retrospectively assessed with a standardized web based questionnaire. A total number of 1962 climbers reported 699 injuries, which is equivalent to 0.2 injuries per 1 000 h of sport participation. Most (74.4%) of the injuries were of minor severity rated NACA I or NACA II. Injury distribution between the upper (42.6%) and lower extremities (41.3%) was similar, with ligament injuries, contusions and fractures being the most common injury types. Years of climbing experience (p<0.01), difficulty level (p<0.01), climbing time per week during summer (p<0.01) and winter (p<0.01) months were correlated with the injury rate. Age (p<0.05 (p=0.034)), years of climbing experience (p<0.01) and average climbing level (p<0.01) were correlated to the injury severity rated through NACA scores. The risk of acute injuries per 1 000 h of sport participation in sport climbing was lower than in previous studies on general rock climbing and higher than in studies on indoor climbing. In order to perform inter-study comparisons of future studies on climbing injuries, the use of a systematic and standardized scoring system (UIAA score) is essential.

Transplanted chondrocytes inhibit endochondral ossification within cartilage repair tissue.

The aim of this study was to investigate the effect of transplanted chondrocytes on endochondral bone formation in cartilage repair tissue. In the knee joint of miniature pigs, cartilage lesions were treated by microfracturing and were then either left empty, covered with a collagen membrane, or treated by matrix-associated autologous chondrocyte transplantation. In control lesions, the subchondral bone plate was left intact (partial-thickness lesion). The repair tissues were analyzed after 12 weeks by histological methods focusing on bone formation and vascularization. The effect of chondrocytes on angiogenesis was assessed by in vitro assays. The presence of antiangiogenic proteins in cartilage repair tissue, including thrombospondin-1 (TSP-1) and chondromodulin-I (ChM-I), was detected immunohistochemically and their expression in chondrocytes and bone marrow stromal cells was measured by quantitative RT-PCR. Significant outgrowths of subchondral bone and excessive endochondral ossification within the repair tissue were regularly observed in lesions with an exposed or microfractured subchondral bone plate. In contrast, such excessive bone formation was significantly inhibited by the additional transplantation of chondrocytes. Cartilaginous repair tissue that resisted ossification was strongly positive for the antiangiogenic proteins, TSP-1 and ChM-I, which were, however, not detectable in vascularized osseous outgrowths. Chondrocytes were identified to be the major source of TSP-1- and ChM-I expression and were shown to counteract the angiogenic activity of endothelial cells. These data suggest that the resistance of cartilaginous repair tissue against endochondral ossification following the transplantation of chondrocytes is associated with the presence of antiangiogenic proteins whose individual relevance has yet to be further explored.

Chondrogenic differentiation of growth factor-stimulated precursor cells in cartilage repair tissue is associated with increased HIF-1alpha activity.

OBJECTIVE: To investigate the chondrogenic potential of growth factor-stimulated periosteal cells with respect to the activity of Hypoxia-inducible Factor 1alpha (HIF-1alpha). METHODS: Scaffold-bound autologous periosteal cells, which had been activated by Insulin-like Growth Factor 1 (IGF-1) or Bone Morphogenetic Protein 2 (BMP-2) gene transfer using both adeno-associated virus (AAV) and adenoviral (Ad) vectors, were applied to chondral lesions in the knee joints of miniature pigs. Six weeks after transplantation, the repair tissues were investigated for collagen type I and type II content as well as for HIF-1alpha expression. The functional role of phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling on BMP-2/IGF-1-induced HIF-1alpha expression was assessed in vitro by employing specific inhibitors. RESULTS: Unstimulated periosteal cells formed a fibrous extracellular matrix in the superficial zone and a fibrocartilaginous matrix in deep zones of the repair tissue. This zonal difference was reflected by the absence of HIF-1alpha staining in superficial areas, but moderate HIF-1alpha expression in deep zones. In contrast, Ad/AAVBMP-2-stimulated periosteal cells, and to a lesser degree Ad/AAVIGF-1-infected cells, adopted a chondrocyte-like phenotype with strong intracellular HIF-1alpha staining throughout all zones of the repair tissue and formed a hyaline-like matrix. In vitro, BMP-2 and IGF-1 supplementation increased HIF-1alpha protein levels in periosteal cells, which was based on posttranscriptional mechanisms rather than de novo mRNA synthesis, involving predominantly the MEK/ERK pathway. CONCLUSION: This pilot experimental study on a relatively small number of animals indicated that chondrogenesis by precursor cells is facilitated in deeper hypoxic zones of cartilage repair tissue and is stimulated by growth factors which enhance HIF-1alpha activity.

Mechanical properties of hyaline and repair cartilage studied by nanoindentation.

Articular cartilage is a highly organized tissue that is well adapted to the functional demands in joints but difficult to replicate via tissue engineering or regeneration. Its viscoelastic properties allow cartilage to adapt to both slow and rapid mechanical loading. Several cartilage repair strategies that aim to restore tissue and protect it from further degeneration have been introduced. The key to their success is the quality of the newly formed tissue. In this study, periosteal cells loaded on a scaffold were used to repair large partial-thickness cartilage defects in the knee joint of miniature pigs. The repair cartilage was analyzed 26 weeks after surgery and compared both morphologically and mechanically with healthy hyaline cartilage. Contact stiffness, reduced modulus and hardness as key mechanical properties were examined in vitro by nanoindentation in phosphate-buffered saline at room temperature. In addition, the influence of tissue fixation with paraformaldehyde on the biomechanical properties was investigated. Although the repair process resulted in the formation of a stable fibrocartilaginous tissue, its contact stiffness was lower than that of hyaline cartilage by a factor of 10. Fixation with paraformaldehyde significantly increased the stiffness of cartilaginous tissue by one order of magnitude, and therefore, should not be used when studying biomechanical properties of cartilage. Our study suggests a sensitive method for measuring the contact stiffness of articular cartilage and demonstrates the importance of mechanical analysis for proper evaluation of the success of cartilage repair strategies.

Stabilization of flail chest injuries: minimized approach techniques to treat the core of instability.

PURPOSE: Stabilizing techniques of flail chest injuries usually need wide approaches to the chest wall. Three main regions need to be considered when stabilizing the rib cage: median-anterior with dissection of pectoral muscle; lateral-axillary with dissection of musculi (mm) serratus, externus abdominis; posterior inter spinoscapular with division of mm rhomboidei, trapezius and latissimus dorsi. Severe morbidity due to these invasive approaches needs to be considered. This study discusses possibilities for minimized approaches to the shown regions. METHOD: Fifteen patients were stabilized by locked plate osteosynthesis (MatrixRib®) between May 2012 and April 2014 and prospectively followed up. Flail chest injuries were managed through limited incisions to the anterior, the lateral, and the posterior parts of the chest wall or their combinations. Each approach was 4-10 cm using Alexis® retractor. RESULTS: One minimized approach offered sufficient access at least to four ribs posterior and laterally, four pairs of ribs anterior in all cases. There was no need to divide latissimus dorsi muscle. Trapezius und rhomboid muscles were only limited divided, whereas a subcutaneous dissection of serratus and abdominis muscles was necessary. A follow-up showed sufficient consolidation. COMPLICATIONS: pneumothorax (2) and seroma (2). CONCLUSION: Minimized approaches allow sufficient stabilization of severe dislocated rib fractures without extensive dissection or division of the important muscles. Keeping the arm and, thus, the scapula mobile is very important for providing the largest reachable surface of the rib cage through each approach.

Bone-implant interface shear modulus and ultimate stress in a transcortical rabbit model of open-pore Ti6Al4V implants.

This experimental study on laser-textured implants aimed to evaluate periimplant bone elasticity and ultimate stress of the bone-implant interface in a rabbit femur model. After randomization, two cylindrical Ti6Al4V samples (3.5 mm wide, 5.5 mm long) were transcortically implanted in each femur of 15 female New Zealand White Rabbits. Polished implants had been laser-textured with 100, 200, and 300 microm diameter pores, and another corundum blasted implant was additionally textured with 200 microm pores. Twelve weeks into the experiment, a modified push-out test was performed. The median shear modulus indicating the elasticity of the periimplant bone was 41.12 MPa for the proximal implant location and 25.38 MPa for the distal, without evidence for significant differences between implant types. Taking into account the median ultimate shear stress for 200 microm implants with and without corundum blasting, no significant difference could be demonstrated. However, for blasted 200 microm implants a statistically significant (p<0.025) relative gain in ultimate shear stress of 41% and 17% was proven in comparison with 100 and 300 microm implants, respectively. Non-blasted 200 microm implants reached 48% relative gain in respect of 100 microm samples.

Evaluation of low-cost computer monitors for the detection of cervical spine injuries in the emergency room: an observer confidence-based study.

BACKGROUND: To compare the diagnostic value of low-cost computer monitors and a Picture Archiving and Communication System (PACS) workstation for the evaluation of cervical spine fractures in the emergency room. METHODS: Two groups of readers blinded to the diagnoses (2 radiologists and 3 orthopaedic surgeons) independently assessed-digital radiographs of the cervical spine (anterior-posterior, oblique and trans-oral-dens views). The radiographs of 57 patients who arrived consecutively to the emergency room in 2004 with clinical suspicion of a cervical spine injury were evaluated. The diagnostic values of these radiographs were scored on a 3-point scale (1 = diagnosis not possible/bad image quality, 2 = diagnosis uncertain, 3 = clear diagnosis of fracture or no fracture) on a PACS workstation and on two different liquid crystal display (LCD) personal computer monitors. The images were randomised to avoid memory effects. We used logistic mixed-effects models to determine the possible effects of monitor type on the evaluation of x ray images. To determine the overall effects of monitor type, this variable was used as a fixed effect, and the image number and reader group (radiologist or orthopaedic surgeon) were used as random effects on display quality. Group-specific effects were examined, with the reader group and additional fixed effects as terms. A significance level of 0.05 was established for assessing the contribution of each fixed effect to the model. RESULTS: Overall, the diagnostic score did not differ significantly between standard personal computer monitors and the PACS workstation (both p values were 0.78). CONCLUSION: Low-cost LCD personal computer monitors may be useful in establishing a diagnosis of cervical spine fractures in the emergency room.

First clinical study of a novel complete metal-free ceramic total knee replacement system.

BACKGROUND: The aim of the study was to evaluate the safety and efficacy of a novel metal-free ceramic total knee replacement system. METHODS: Thirty-eight primary total knee arthroplasties (TKAs) were performed on 34 patients using the metal-free BPK-S ceramic total knee replacement system with both the femoral and tibial components of an alumina/zirconia ceramic composite. The clinical outcome was evaluated pre- and postoperatively at 3 (n = 32 TKA) and 12 months (n = 32 TKA) using the Knee Society Score (KSS), the Oxford Knee Score and the EQ-5D. Safety analysis was performed by radiological examination and assessment of adverse events. RESULTS: Postoperatively, the KSS, Oxford Knee Score and EQ-5D improved significantly at 3 and 12 months (p < 0.001). Non-progressive partial radiolucent lines were observed in six cases, but there was no osteolysis and no implant loosening. Induction or exacerbation of allergies did not occur during the follow-up. CONCLUSIONS: The metal-free BPK-S ceramic total knee replacement system proved to be a safe and clinically efficient alternative to metal implants in this short-term follow-up study.

Effect of acute brain death on release of atrium and B-type natriuretic peptides in an animal model.

INTRODUCTION: Atrium and B-type natriuretic peptides (ANP and BNP) and big endothelin (ET)-1 are markers for severity of heart failure and may be used in the quality assessment of donor hearts. Elevated cardiac troponins predict early graft failure after heart transplantation. This study evaluated the effects of acute brain death (BD) on the release of ANP, BNP, big ET-1, and cardiac troponins in an animal model. MATERIALS AND METHODS: Pigs were randomized into a BD group (n=5) and a control group (n=5). In the first group, acute BD was induced, and anesthesia was stopped. In the control animals, a sham operation was performed, and anesthesia was continued. Parameters were measured at baseline and for 13 hours postoperatively. RESULTS: After acute BD, there were significant hemodynamic changes. In the control group, the BNP level was higher than in the BD group and decreased over time (P =0.016). There was no significant change in BNP release in the BD group up to 13 hours (P =0.1). ANP release remained stable over time in the control group (P =0.35) but decreased in the BD group (P =0.043). The big ET-1 levels were not different between groups. Cardiac troponin I was elevated in the BD group 5 hours after BD (P< 0.05) but remained under 1.5 mg/L throughout the study. CONCLUSION: Acute BD did not lead to an increase of BNP and ANP levels. Moreover, intact brain function seems to augment the release of natriuretic peptides from the myocardium. Further clinical evaluation of prognostic values of natriuretic peptides for the assessment of donor hearts is necessary. Cardiac troponins are a useful additional tool in the evaluation of donor hearts.

Quantitative determination of chromium and nickel in tumour and tumour-free human tissue.

Environmental pollution with carcinogenic substances, in addition to individual abuse, are discussed as important factors causing development of cancer. We must assume that certain nickel and chromium compounds, which are ubiquitous in our ecosystem, must have carcinogenic effects on humans too. The aim of this study is therefore to examine the extent to which the accumulation of the potentially carcinogenic metal ions nickel and chromium could be measured in tissue from tumour patients. We examined tumour and tumour-free tissue obtained from a total of 48 patients who had carcinomas of the stomach, bowel, or kidney. We also analyzed nickel and chromium content in whole blood and urine samples from these persons. The quantitative metal estimations were done using atomic absorption spectrophotometry. Differences between chromium and/or nickel content in tumour or tumour-free tissue were not observed. An accumulation of these metal ions in tumour tissue is therefore improbable. We were also unable to find differences in metal content with regard to chromium and nickel as related to the appearance of tumour in the organ. In contrast, tumour patients had a 5- to 7-fold increase over normal values for chromium and nickel in blood and urine. This was attributable to unavoidable contamination of tissue and body fluids with chromium- and nickel-containing instruments during major surgical procedures.

Comparison of 3,000 IU aXa of the low molecular weight heparin certoparin with 5,000 IU aXa in prevention of deep vein thrombosis after total hip replacement. German Thrombosis Study Group.

BACKGROUND: The aim of this randomized, double-blind and prospective clinical trial was to investigate whether an increase of the conventional daily dosage (3,000 IU aXa) of the low molecular weight heparin certoparin up to 5,000 IU aXa/day might lower the incidence of deep vein thrombosis (DVT) in patients undergoing elective hip surgery. METHODS: The main criterium of this trial was the incidence of DVT diagnosed by bilateral ascending venography, which was performed either if DVT was clinically suspected or in each remaining patient between the 12th and the 14th postoperative day. A total number of 172 patients were enrolled to receive the conventional dosage of 3,000 IU aXa (Mono-Embolex NM) and 169 patients to receive the high dosage form (5,000 IU aXa) once daily. The mean age (+/-SD) was 69.6+/-9.5 and 67+/-11.7 years. RESULTS: No relevant differences were found concerning predisposing risk factors. The duration of surgery was 93+/-25.2 and 88+/-21.4 min (mean+/-SD). Surgical type and approach were not different between the groups. Deep vein thrombosis was detected in 17 patients (9.9%) in the conventional dose group and in 16 patients (9.5%) in the high dose group (intent-to-treat analysis; n.s.). The rate of bleeding complications was not significantly different except the cell saver volumes (770+/-136 vs 475+/-186 ml; p<0.001). No significant difference was found in the serious adverse event reporting along the lines of EC-GCP (10 vs 8 events; p=0.65). CONCLUSIONS: This clinical trial confirmed that the conventional dosage (3,000 IU aXa/day) of certoparin ensures maximal antithrombotic activity.