[Clinical management of rotator cuff tears. Current concepts in cell-based therapy strategies]. / Klinische Versorgung von Rupturen der Rotatorenmanschette. Aktueller Stand der Zelltherapie.

Due to the increasing demand for functionality in an aging yet physically active society, the treatment of rotator cuff tears is of ever-growing importance. Despite intensive research efforts, the treatment of degenerative rotator cuff tears, in particular their long-term outcome, is still a challenge. While in recent years the focus was on biomechanics and the technical aspects of rotator cuff reconstruction, attention has now turned to the biological considerations of tendon regeneration. This article highlights the current state of biological rotator cuff augmentation in a clinical setting and provides an insight into and an outlook on the experimental procedures.

[Quality of life and job performance resulting from operatively treated tibial plateau fractures]. / Lebensqualität und Arbeitsfähigkeit nach operativer Behandlung von Tibiakopffrakturen.

BACKGROUND: The aim of this article is to present the functional results and the effect on quality of life of surgically treated tibial plateau fractures in physically active and working patients with multiple and serious injuries. In addition, the relationships between functional and radiological outcome were evaluated and compared with activity in daily and professional life. PATIENTS AND METHODS: In all, 41 injured patients were followed up a mean of 47 months after surgical treatment and examined with radiological, functional, as well as quality of life score. RESULTS: In the radiological scoring, a mean value of 72 points (max 100 points) was achieved. In the activity score, there was an average of 63.5 points (max 100 points). When evaluating the health-related quality of life, an average score of 69.6 points was achieved. There was a significant relationship between radiological and activity scores and the radiological and life quality scores. Furthermore, the relationship between activity and quality of life scores was considered significant. Surgeon's influence on the functional outcome could be confirmed. CONCLUSION: The functional and the radiological results were moderate. Quality of life was permanently affected by the consequences of tibial plateau fracture in 12 patients; 11 patients were not re-employed. However, the quality of life was assessed as good or very good and 28 patients had returned to work. The quality of life was firmly linked to the radiological and functional parameters, which tended to be influenced by the quality of the primary surgical treatment when looking at the overall population.

No acute effects of an exposure to 50 ppm methyl methacrylate on the upper airways.

PURPOSE: The German MAK value of methyl methacrylate has been fixed at 50 ppm. The aim of this study was to evaluate possible acute effects of an exposure to 50 ppm methyl methacrylate on the upper airways of human subjects. METHODS: Twenty healthy subjects were exposed to 50 ppm methyl methacrylate and to air (sham) in an exposure chamber for 4 h according to a crossover design. Symptoms were assessed by the SPES questionnaire. Olfactory thresholds for n-butanol and mucociliary transport time were measured before and after exposure. Concentrations of interleukin 1ß and interleukin 8 were determined in nasal secretions taken after exposure. mRNA levels of interleukins 1ß, 6 and 8, tumor necrosis factor α, granulocyte-macrophage colony-stimulating factor, monocyte chemotactic protein 1, and cyclooxygenases 1 and 2 were measured in nasal epithelial cells, obtained after exposure. Possible effects were investigated by semiparametric and parametric crossover analyses. RESULTS: The score of the item "irritation to the nose" was slightly elevated following exposure to methyl methacrylate (p ≤ 0.01). Olfactory functioning was not impaired. Mucociliary transport time did not change. Neither concentrations of interleukins in nasal secretions nor mRNA levels were elevated. CONCLUSION: Only minor irritating effects on the nose were observed. The acute exposure to 50 ppm methyl methacrylate did not cause any adverse effects. However, the results cannot be extrapolated to chronic exposure.

Tissue characteristics in tendon-to-bone healing change after rotator cuff repair using botulinumneurotoxin A for temporary paralysis of the supraspinatus muscle in rats.

We hypothesized that botulinumneurotoxin A (BoNtA) positively influences tissue characteristics at the re-insertion site when used as an adjuvant prior to rotator cuff repair. One hundred and sixty Sprague-Dawley rats were randomly assigned to either a BoNtA or saline-injected control group. BoNtA or saline solution was injected into the supraspinatus muscle one week prior to repair of an artificially created supraspinatus tendon defect. Post-operatively, one subgroup was immobilized using a cast on the operated shoulder while the other had immediate mobilization. Histologically, the fibrocartilage transition zone was more prominent and better organized in the BoNtA groups when compared to the saline control group. In the immediately mobilized BoNtA groups significantly more collagen 2 at the insertion was detected than in the control groups (p<0.05). Fiber orientation of all BoNtA groups was better organized and more perpendicular to the epiphysis compared with control groups. Tendon stiffness differed significantly (p<0.05) between casted BoNtA and casted saline groups. Tendon viscoelasticity was significantly higher (p<0.05) in the immobilized saline groups no matter if repaired with increased or normal repair load. The results of this study suggest that reduction of load at the healing tendon-to-bone interface leads to improved repair tissue properties.

Polyethylene wear particles induce TLR 2 upregulation in the synovial layer of mice.

A cellular and receptor mediated response to ultra-high-molecular-weight-polyethylene (UHMWPE) wear particles results in a release of proinflammatory cytokines and induces an inflammatory reaction causing osteolysis in total joint replacement. This investigation offers insight into the toll-like receptor (TLR) mediated activation by polyethylene wear particles in the synovial layer of mice. We hypothesized that, similar to recent in vitro results, UHMWPE particles lead to an upregulation of TLR 1 and 2 and TLR 4 in vivo in the synovial tissue of mice as well. Therefore, UHMWPE particles were generated in a common knee simulator according to the ISO standard, separated by acid digestion and determined by scanning electron microscopy. Endotoxin was removed using a method based on ultracentrifugation. A particle suspension (50 µl; 0.1 vol./vol.%) was injected into the left knee joint of female Balb/c mice (n = 8). In a control group, phosphate-buffered saline was injected into the left knee of Balb/c mice (n = 8). The mice were sacrificed after 7 days. Immunohistochemical staining was performed with TLR 1, 2 and 4 polyclonal antibodies for Balb/c mice and evaluated by light microscopy. The particle-stimulated group showed a thickened synovial layer, an increased cellular infiltration and a TLR 2-upregulation in the synovial layer compared to the control group. An increased expression of TLR 1 and TLR 4 could not be demonstrated. These results indicate a mainly TLR 2-induced inflammation to polyethylene wear debris in the synovial layer of mice.

In vivo ozone exposure does not increase DNA single-strand breaks in human peripheral lymphocytes.

In this randomized parallel study, we examined whether an acute ozone (O3) exposure leads to increased DNA strand breaks in human lymphocytes. The groups were exposed to 0.21 ppm O3 or filtered air for two hours. 30min and 4.5 h after exposure, DNA damage was determined in isolated lymphocytes using the Fast Micromethod. There was no detectable effect after O3 exposure. We conclude that an acute O3 exposure at the tested concentration does not lead to persistent DNA damage.

Acute effects of an exposure to 100 ppm 1-methoxypropanol-2 on the upper airways of human subjects.

The German MAK value of 1-methoxypropanol-2 has been fixed at 100 ppm. The aim of this study was to evaluate possible acute effects of an exposure to 100 ppm 1-methoxypropanol-2 on the upper airways of human subjects. Twenty subjects were exposed in a crossover design to 100 ppm 1-methoxypropanol-2 and to air in an exposure chamber for 4h. Subjective symptoms were assessed by questionnaire. Olfactory thresholds for n-butanol and mucociliary transport time were measured before and after exposure. Concentrations of interleukin 1ß and interleukin 8 were determined in nasal secretions taken after exposure. mRNA levels of interleukins 1ß, 6 and 8, tumor necrosis factor α, granulocyte-macrophage colony-stimulating factor, monocyte chemotactic protein 1, and cyclooxygenases 1 and 2 were measured in nasal epithelial cells, obtained after exposure. Possible effects were investigated by semiparametric and parametric cross-over analyses. Subjects did not have any subjective irritating symptoms. The olfactory threshold was slightly elevated following exposure to 1-methoxypropanol-2. Mucociliary transport time did not change. Neither concentrations of interleukins in nasal secretions nor mRNA levels except for interleukin 1ß were higher after exposure to 1-methoxypropanol-2. In conclusion, the acute exposure to 100 ppm 1-methoxypropanol-2 did not cause clear-cut adverse effects in test subjects.

Effects of an acute exposure to toluene on the DNA repair activity of the human 8-oxoguanine DNA glycosylase 1 (hOGG1) in healthy subjects.

The structure and previous studies on the biotransformation of toluene lead to the suspicion that metabolites may be formed which preferentially react with strongly nucleophilic partners such as sulfhydryl groups of cysteines in proteins. Human 8-oxoguanine DNA glycosylase 1 removes the major oxidative DNA damage and possesses eight cysteines. Its potential inactivation may lead to accumulation of DNA damage by reactive oxygen species formed by exogenous agents or by ubiquitous endogenous processes. The goal of the present investigation was to study the in vivo effect in humans of an acute toluene exposure on hOGG1 activity. Twenty healthy, non-smoking males were exposed to 50 ppm toluene and to filtered air in an exposure chamber for 270 min, using a cross-over design. Before and 30 min after the end of exposure, blood samples were taken and toluene concentrations and the hOGG1 activity were measured. hOGG1 activity was determined in peripheral mononuclear blood cells. Thirty minutes after exposure to toluene, we found a median blood concentration of 0.25 mg toluene/l. Compared with the activity before exposure, upon exposure to toluene a statistically insignificant median increase of hOGG1 activity by +0.4% and upon exposure to air by +2.3% was determined. Thus, no reduction of the hOGG1 repair activity after acute exposure to 50 ppm toluene was observed.

Longitudinal study on potential neurotoxic effects of aluminium: II. Assessment of exposure and neurobehavioral performance of Al welders in the automobile industry over 4 years.

OBJECTIVES: This is the second of two parallel longitudinal studies investigating Al exposure and neurobehavioral health of Al welders over 4 years. While the first published study in the trail and truck construction industry examined the neurobehavioral development of Al welders from age 41-45 in the group mean (Kiesswetter et al. in Int Arch Occup Environ Health 81:41-67, 2007), the present study in the automobile industry followed the development from 35 to 39. Although no conspicuous neurobehavioral developments were detected in the first study, which furthermore exhibited the higher exposure, it cannot be excluded that exposure effects appear in earlier life and exposure stages. METHODS: The longitudinal study is based on a repeated measurement design comprising 4 years with three measurements in 2 years intervals. 92 male Al welders in the automobile industry were compared with 50 non-exposed construction workers of the same industry and of similar age. The repeated measurements included total dust in air, and Al pre- and post-shift plasma and urine samples. Neurobehavioral methods comprised symptoms, verbal intelligence, logic thinking, psychomotor behavior, memory, and attention. The computer aided tests came from the Motor Performance Series and the European Neurobehavioral Evaluation System. The courses of neurobehavioral changes were analyzed with multivariate covariance-analytical methods considering the covariates age, indicators of 'a priori' intelligence differences (education or markers of 'premorbid' intelligence), and alcohol consumption (carbohydrate-deficient transferrin in plasma). Additionally, the interrelationship, reliability and validity of biomonitoring measures were examined. RESULTS: The mean environmental dust load during welding, 0.5-0.8 mg/m(3), and the mean internal load of the welders (pre-shift: 23-43 microg Al/g creatinine in urine; 5-9 microg Al/l plasma) were significantly lower than in the parallel study. Under low exposure, the stability of biomonitoring measures was reduced, but the Al load differed significantly between Al welders and referents. It could not be shown that the development of neurobehavioral performances over the 4-year period differed between both groups. Mainly, markers of premorbid intelligence and age were related to neurobehavioral performance differences but not Al exposure. CONCLUSIONS: The biomonitoring and neurobehavioral results are in line with the results of the first published study. The repeated measurement models of both studies showed no adverse neurobehavioral effects of Al welding. A modular lifetime-oriented research concept is outlined aiming at the investigation of sequential periods of exposure life with special focus on the biologically most sensitive phases like first exposure and old age.

No acute effects of an exposure to 50 ppm acetaldehyde on the upper airways.

OBJECTIVE: German MAK value of acetaldehyde has been fixed at 50 ppm to prevent from irritating effects. The threshold value is mainly based on animal experiments. The aim of this study was to evaluate acute effects of an exposure to 50 ppm acetaldehyde on the upper airways of human subjects. METHODS: Twenty subjects were exposed to 50 ppm acetaldehyde and to air in an exposure chamber for 4 h according to a crossover design. Subjective symptoms were assessed by questionnaire. Olfactory threshold for n-butanol and mucociliary transport time were measured before and after exposure. Concentrations of interleukin 1beta and interleukin 8 were determined in nasal secretions taken after exposure. mRNA levels of interleukins 1beta, 6 and 8, tumour necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, monocyte chemotactic protein 1, and cyclooxygenases 1 and 2 were measured in nasal epithelial cells, gained after exposure. Possible effects were investigated by semiparametric and parametric crossover analyses. RESULTS: Exposure to acetaldehyde did not cause any subjective irritating symptoms. Olfactory threshold did not change. Mucociliary transport time increased insignificantly after exposure to acetaldehyde. Neither concentrations of interleukins in nasal secretions nor mRNA levels of inflammatory factors were higher after exposure to acetaldehyde. CONCLUSION: An acute exposure to 50 ppm acetaldehyde did not cause any adverse effects in test subjects.

3-Hydroxybenzo[a]pyrene in the urine of workers with occupational exposure to polycyclic aromatic hydrocarbons in different industries.

OBJECTIVES: This study was conducted to assess external and internal exposure of workers to polycyclic aromatic hydrocarbons (PAHs). In this context, the analytical and diagnostical reliability of 3-hydroxybenzo[a]pyrene (3OH-BaP) as a biomarker of internal exposure to PAHs was established. METHODS: Ambient and biological monitoring was carried out of 225 PAH-exposed employees of different industries. External exposure was determined by personal air sampling and analysis of 16 EPA-PAH. Internal exposure was examined by the urinary metabolites 3OH-BaP, 1-hydroxypyrene (OH-Pyr) and monohydroxylated phenanthrenes (OH-Phens). RESULTS: Benzo[a]pyrene (BaP) was detected at all workplaces. Concentrations in the breathing zone of the workers ranged from below the limit of detection up to 44.3 mug/m(3). In biological monitoring, urinary 3OH-BaP was found in median concentrations of 0.8 ng/g creatinine (crea) and the 95th percentile of 6.7 ng/g crea. The results ranged from the limit of detection up to 19.5 ng/g crea. Only 1% of the analysed samples showed concentrations below the limit of detection (0.05 ng/l). Regarding median concentrations, workers in coking plants showed lower 3OH-BaP concentrations (0.5 ng/g crea) than those employed in the production of fireproof material in refractories (1.1 ng/g crea), converter infeed (1.2 ng/g crea) and graphite electrode production (1.3 ng/g crea). Strong correlations of 3OH-BaP with OH-Pyr and the sum of OH-Phens were found for the workplaces converter infeed, coking plants and graphite electrode production (r(Pearson) ranging from 0.618 to 0.867, p<0.001). The poor correlation of BaP in the air and 3OH-BaP in urine is most probably caused by routes of uptake other than via air-for example, dermal uptake. CONCLUSION: 3OH-BaP as a metabolite of the carcinogenic BaP could be shown to be a diagnostically specific and sensitive biomarker for determining the internal exposure of workers in different industries. Using this method, the estimation of health risks for workers can be fundamentally improved, because the 3OH-BaP represents the group of carcinogenic PAHs. The procedure for analysing 3OH-BaP is complex, but it is robust and produces reliable results.

Longitudinal study on potential neurotoxic effects of aluminium: I. Assessment of exposure and neurobehavioural performance of Al welders in the train and truck construction industry over 4 years.

OBJECTIVES: Previous cross sectional studies on potential neurotoxic effects of long-term aluminium exposures by aluminium welders lack clear interpretable results for methodological reasons. The present longitudinal study examined on the one hand the reliability and representativity of Al-biomonitoring as indicator of individual long-term exposure and on the other hand the long-term changes of neurobehavioural performance in Al welders in relation to Al exposure and neurobehavioural performance changes of a non-exposed control group. METHODS: The longitudinal study compared repeatedly measured exposure data and neurobehavioural data of 20, initially 44, male Al welders in the train and truck construction industry with data of a control group of similar age on the basis of three investigations over a period of 4 years. The repeated measurements of exposure included total dust in air as well as Al in pre- and post-shift plasma and urine samples. Neurobehavioural methods comprised symptoms, verbal intelligence, logic thinking, psychomotor behaviour, memory, and attention. Computer-aided tests from the Motor Performance Series (MLS) and the European Neurobehavioural Evaluation System (EURO-NES) were used. The characteristics of the biomonitoring data and the relationship to neurobehavioural data were examined with methods of correlation and regression analysis. The courses of neurobehavioural changes were analysed with multivariate covariance-analytical methods (MANCOVA) considering the covariates age, indicators of 'a priori' intelligence differences (education or 'premorbid' intelligence), and alcohol consumption (carbohydrate-deficient transferrin in plasma, CDT). RESULTS: The mean total dust load during welding, near to the routinely worn ventilated helmets, was in the range of 5-8 mg/m(3). The biomonitoring data of the welders (pre-shift: 88-140 microg Al/g creatinine in urine; 13-16 microg Al/l plasma) showed a high long-term stability but also sensitivity to acute shift dependent exposure changes. The Al welders who had been working in this profession at an average of 15 years showed no significantly increased symptom levels compared with the control group. Explorative regression and covariance analyses revealed neither a correlation between biomonitoring and performance variables nor a significant difference between Al-exposed and controls in the performance courses during the 4 years period. Explorative modelling indicated that the structure of neurobehavioural outcomes could be determined by possible indicators of intellectual 'a priori' (premorbid) differences between subjects but not by their exposure information. CONCLUSIONS: Compared to studies in the literature this study is characterized by relatively high and non-confounded Al exposure of the welders, a repeated-measurement design, and multivariate analyses. However, the long-term stable interindividual differences of internal Al exposure were not related to interindividual differences in neurobehavioural performances. Additionally, the lack of processual changes of neurobehavioural performances during the observation phase and the insignificant group differences do not make it very probable that degenerative processes caused by Al had happened before study onset or stopped just at this time point.

Ambient and biological monitoring of coke plant workers -- determination of exposure to polycyclic aromatic hydrocarbons.

OBJECTIVES: The aims of this study were to determine external and internal polycyclic aromatic hydrocarbon (PAH) exposure in a coke plant and to contribute to the evaluation of biological limit values. METHODS: Personal air sampling was carried out on a study population of 24 coke plant workers. In detail, 16 PAHs were determined, among them phenanthrene, pyrene and benzo[ a]pyrene. For the determination of internal exposure, post-shift urine samples from the workers were examined for hydroxylated metabolites of pyrene (1-hydroxypyrene, 1-OHP) and phenanthrene (1-, 2+9-, 3-, 4-hydroxyphenanthrene, 1-, 2+9-, 3-, 4-OHPhe). In both cases, approved HPLC methods were used. RESULTS: The workers were classified into three groups. The group most exposed was that on the top side of the coke oven, with a mean value of 491.2 microg/m(3) for the sum of all sixteen PAHs. The mean value at the bench side was 26.61 microg/m(3), while it was 76.18 microg/m(3) in the group of workers with no dedicated location (=complete area). Both the excretion of 1-OHP and the sum of hydroxyphenanthrenes had the highest mean levels in the top side group of workers (mean: 19.70 microg/g creatinine (crea.) and 39.18 microg/g crea.), followed by the bench-side workers (mean: 7.01 microg/g crea. and 12.95 microg/g crea.) and the whole-area workers (mean: 3.57 microg/g crea. and 8.70 micorg/g crea.). The concentrations of all urinary metabolites correlated significantly with benzo[ a]pyrene (BaP) in the air. CONCLUSIONS: According to these correlations, urinary concentrations of 8 and 11 microg 1-OHP/g crea., respectively 16 and 23 microg/g crea. for the sum of hydroxyphenanthrenes, correspond to BaP concentrations in air of 2 and 5 micorg/m(3), the German technical guiding concentration (TRK value). Our results are in line with others reported in the literature. That means that it should be possible today to define a standard of occupational hygiene and medicine in coke plants using the elimination of hydroxyphenanthrenes and hydroxypyrene in urine as markers for internal PAH exposure.

Analysis of 8-oxo-7,8-dihydro-2'-deoxyguanosine and DNA strand breaks in white blood cells of occupationally exposed workers: comparison with ambient monitoring, urinary metabolites and enzyme polymorphisms.

The relationship between biomarkers of effect (8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo, HPLC system) and tail extent moment (comet assay)), markers of external and internal exposure, and biomarkers of susceptibility was evaluated for coke-oven and graphite-electrode-producing plant workers exposed to polycyclic aromatic hydrocarbons (PAHs). Mean 8-oxodGuo levels in white blood cells (WBC) of exposed workers were between 1.38 times (coke-oven, n = 20; P < 0.01) and 2.15 times (graphite-electrode-producing plant, n = 30; P < 0.01) higher than levels found in control samples (mean +/- SD 0.52 +/- 0.16 8-oxodGuo/10(5) dGuo, n = 47). The mean tail extent moment in lymphocytes was 1.38 times higher for coke-oven workers (n = 19; P = 0.09) and 3.13 times higher for graphite-electrode-producing plant workers (n = 29; P < 0.01) when compared with controls (mean plus minus SD 2.54 +/- 0.68, n = 32). Elevated tail extent moments (>3.73) were found in the majority (84%) of PAH-exposed workers showing increased DNA adduct levels (>0.78 8-oxodGuo/10(5) dGuo). However, no association (P > 0.05) was found between DNA damage (8-oxodGuo/10(5) dGuo or tail extent moment) in WBC of all PAH-exposed workers and either benzo[a]pyrene levels or the sum of 16 PAH levels in the air at work place. Furthermore, no relation (P > 0.05) could be established between DNA damage in WBC and biomarkers of internal exposure (1-hydroxypyrene (1-OHP) and sum of five hydroxyphenanthrenes (OHPHs)). Higher exposure to airborne pyrene and phenanthrene led to increasing concentrations of the metabolites 1-OHP (P < 0.01) and the sum of five OHPHs (P < 0.01) in the urine of PAH-exposed workers. The polymorphisms of genes CYP1A1, GSTM1, GSTT1 and GSTP1 (biomarkers of susceptibility) showed no association with biomarkers of effect. In conclusion, both biomarkers of effect may be appropriate for further surveillance studies of workers under PAH exposure.