Biochemical cartilage alteration and unexpected signal recovery in T2* mapping observed in ankle joints with mobile MRI during a transcontinental multistage footrace over 4486 km.

OBJECTIVE: The effect of ultra-long distance running on the ankle cartilage with regard to biochemical changes, thickness and lesions is examined in the progress of a transcontinental ultramarathon over 4486 km. METHOD: In an observational field study, repeated follow-up scanning of 22 participants of the TransEurope FootRace (TEFR) with a 1.5 T MRI mounted on a mobile unit was performed. For quantitative biochemical and structural evaluation of cartilage a fast low angle shot (FLASH) T2* weighted gradient-echo (GRE)-, a turbo-inversion-recovery-magnitude (TIRM)- and a fat-saturated proton density (PD)-weighted sequence were utilized. Statistical analysis of cartilage T2* and thickness changes was obtained on the 13 finishers (12 male, mean age 45.4 years, BMI 23.5 kg/m²). None of the nine non-finisher (eight male, mean age 53.8 years, BMI 23.4 kg/m²) stopped the race due to ankle problems. RESULTS: From a mean of 17.0 ms for tibial plafond and 18.0 ms for talar dome articular cartilage at baseline, nearly all observed regions of interest (ROIs) of the ankle joint cartilage showed a significant T2*-signal increase (25.6% in mean), with standard error ranging from 19% to 33% within the first 2500 km of the ultra-marathon. This initial signal behavior was followed by a signal decrease. This signal recovery (30.6% of initial increase) showed a large effect size. No significant morphological or cartilage thickness changes (at baseline 2.9 mm) were observed. CONCLUSION: After initial T2*-increase during the first 2000-2500 km, a subsequent T2*-decrease indicates the ability of the normal cartilage matrix to partially regenerate under ongoing multistage ultramarathon burden in the ankle joints.

[MRI changes of Achilles tendon and hindfoot in experienced runners and beginners during training and after a (half)-marathon competition]. / MR-tomografische Veränderungen an Achillessehne und Rückfuß von Laufanfängern und Lauferfahrenen im Trainingsverlauf und nach einem (Halb-)Marathon.

BACKGROUND: Marathon running is gaining in popularity. Its benefits regarding the cardiovascular system as well as the metabolism are beyond doubt. However, whether or not there are detrimental side effects to the musculoskeletal system such as wear and tear is an unsolved question. We therefore prospectively looked at beginners and experienced runners at a city marathon during training and after the competition for lesions to the Achilles tendon (AT) or hindfoot. MATERIAL AND METHOD: 73 healthy subjects were prospectively included in our study. They were recruited from the applicants of the city marathon or half-marathon. They underwent an initial clinical orthopaedic as well as three magnetic resonance (MRI) examinations. The MRI were conducted at the time point of study enrolment, near the end of training and directly (up to 72 hours) after the run. MRI evaluation (fat saturated T (2)-weighted sagittal STIR sequence) was performed by two independent experienced radiologists blinded to the clinical context. The results were compared for subgroups of runners, also a factorial analysis was performed. Statistical results were deemed significant for p ≤ 0.05. RESULTS: 32 women and 41 men were included. In the end there were 53 finishers and 20 non-finishers; 28 seasoned runners and 25 novices. 57 runners had no foot complaints, while 14 had foot pain during training and 13 during the marathon. Mean body weight was 71.6 kg, height was 173 cm, age was 40.2 years. Mean AT diameter was 7.0 mm and showed no change during training or after the marathon. There was no significant influence of gender on other variables investigated. There was a significant and positive correlation between AT diameter and weight (r = 0.37), also AT and height (r = 0.34), while there was negative correlation between height and signal intensity of calcaneus (r = -0.50). The signal intensity of the AT decreased during training. The signal intensity of the calcaneus decreased from inclusion until after the marathon, while the mean retrocalcanear bursa volume and AT lesion volume increased. Some of the non-finishers stopped the training because of orthopaedic symptoms. These runners generally had an apparent lesion visible in their initial MRI examination. Regarding the factorial analysis of the data, there were no risk factors predicting non-finishing or development of new lesions to be detected. Interrater reliability was moderate for retrocalcanear bursa, while it was good to excellent for AT diameter and calcaneus MR signal intensity. CONCLUSION: In our sample of primarily asymptomatic German runners, the AT diameter was higher than in symptomatic American patients. The diameter did not change during training or after the marathon. Non-finishers with orthopaedic reasons generally had a lesion on MRI in the initial examination. Apart from this, no new lesions to the AT or hindfoot are to be expected during normal training. Adaptive processes seem to be the main effect of this training.

[Differentiation of coding quality in orthopaedics by special, illustration-oriented case group analysis in the G-DRG System 2005]. / Differenzierung der Codierqualität in der Orthopädie durch spezielle abbildungsorientierte Fallgruppenanalyse im G-DRG-System 2005.

AIM: We introduce a grouping system for clinical practice which allows the separation of DRG coding in specific orthopaedic groups based on anatomic regions, operative procedures, therapeutic interventions and morbidity equivalent diagnosis groups. With this, a differentiated aim-oriented analysis of illustrated internal DRG data becomes possible. METHODS: The group-specific difference of the coding quality between the DRG groups following primary coding by the orthopaedic surgeon and final coding by the medical controlling is analysed. In a consecutive series of 1600 patients parallel documentation and group-specific comparison of the relevant DRG parameters were carried out in every case after primary and final coding. RESULTS: Analysing the group-specific share in the additional CaseMix coding, the group "spine surgery" dominated, closely followed by the groups "arthroplasty" and "surgery due to infection, tumours, diabetes". Altogether, additional cost-weight-relevant coding was necessary most frequently in the latter group (84%), followed by group "spine surgery" (65%). In DRGs representing conservative orthopaedic treatment documented procedures had nearly no influence on the cost weight. CONCLUSIONS: The introduced system of case group analysis in internal DRG documentation can lead to the detection of specific problems in primary coding and cost-weight relevant changes of the case mix. As an instrument for internal process control in the orthopaedic field, it can serve as a communicative interface between an economically oriented classification of the hospital performance and a specific problem solution of the medical staff involved in the department management.

[Significance of a coding engaged orthopaedic surgeon for the illustration quality and compensation of an orthopaedic university department in the German DRG System 2005]. / Bedeutung eines Codierbeauftragten Facharztes für die Abbildungsqualität und Vergütung einer orthopädischen Universitätsklinik im G-DRG-System 2005.

AIM: In the year 2005 the German DRG system underwent further differentiation in many areas compared to previous years. The effects of an improved coding quality by a specifically trained orthopaedic surgeon (KBFA) at an orthopaedic university department are analysed. METHODS: In a closed sample of 1 277 cases the following parameters were documented after primary coding at discharge and after the final coding by the KBFA: main diagnosis, number of additional diagnoses and procedures, the resulting G-DRG, PCCL, cost weight and revenues. These data were analysed for statistically significant differences and correlations. RESULTS: The final coding by the KBFA caused a significant (p<0.001) increase in the number of diagnoses and procedures. The intervention of the KBFA changed the DRG grouping in 34 % of the cases. The cost weight increased significantly and the case mix index raised by 0.26 in the complete sample, corresponding to an increased revenue of euro 62 per case and day. CONCLUSIONS: The establishment of a KBFA in an orthopaedic department improved the quality of revenue-relevant DRG coding and the reflection of the economic complexity level of the cases. Compared to other reports, an above-average increase of cost weight as well as specification depth for diagnoses and procedures was achieved.

Expression of the alpha4 isoform of the nicotinic acetylcholine receptor in the fetal human cerebral cortex.

Nicotinic acetylcholine receptors are likely to play an important role in neuronal migration during development. Furthermore, the alpha4 receptor subunit gene is related to a hereditary juvenile form of epilepsy. Only little information is available, however, on the expression of cerebrocortical nicotinic acetylcholine receptors during human fetal development. Using non-isotopic in situ hybridization and immunohistochemistry, we have studied the distribution of the alpha4 subunit of the nicotinic acetylcholine receptor mRNA and protein in the human frontal cortex at middle (17-24 weeks of gestation) and late (34-42 weeks of gestation) fetal stages. Both, alpha4 receptor mRNA and alpha4 receptor protein were observed beginning during week 17-18 of gestation. At this time of development, a few weakly labeled mRNA-containing cells were present mainly in the ventricular zone, the subplate and the cortical plate. A similar distribution pattern was found for the receptor protein. Around week 38 of gestation, the distribution in the cerebral cortex of alpha4 subunit-containing cells was similar to that of adult human cortices with the highest densities of labeled neurons found in layers II/III, followed by layers V and VI. Nicotinic acetylcholine receptor-containing neurons appear rather early in human fetal development. Given functional maturity, they may interact during cortical development with acetylcholine released from corticopetal fibers or other yet unknown sources subserving the process of neuronal migration and pathfinding.

[Intermediate term outcome of of a hip prosthesis revision system]. / Mittelfristige Ergebnisse mit einem Hüftschaftrevisionssystem.

The Zweymüller shaft for uncemented total hip arthroplasty was developed in the early 1970s. Encouraged by the clinical results with this stem, which was mainly used in primary arthroplasty, longer fitting stems were added to the line to accommodate bony defects and to allow for an optimal load transfer from proximal to distal. The principal of the design is to allow an optimal distal fixation while allowing the bone to remodel in the proximal part. This study reports on 89 patients who underwent revision surgery of the hip for mostly aseptic loosening. The results after a median follow-up of 36 months show an increase of the modified Harris hip score from 52 points pre- to 82 points postoperatively. Radiographic subsidence was found in nine cases, with eight having progressed for more then 3 mm. Postoperative complications occurred in 11.2%, with seven dislocations. Open revision became necessary in two cases. The stem reviewed here seems to achieve predictable results in cases where a proximal cone is still present to facilitate load transfer, while at the same time the quadrangular stem provides solid distal fixation and ensures rotary stability.

Parvalbumin-containing interneurons of the human cerebral cortex express nicotinic acetylcholine receptor proteins.

Cholinergic fibers from the basal forebrain are known to contact cholinoceptive cortical pyramidal neurons. Recent electrophysiological studies have revealed that nicotinic acetylcholine receptors are also present in human cerebrocortical interneurons. A direct visualization of nicotinic receptor subunits in cortical interneurons has, however, not yet been performed. We have applied double-immunofluorescence using antibodies against parvalbumin --a marker for the Chandelier and basket cell subpopulation of interneurons--and to the alpha4 and alpha7 subunit proteins of the nicotinic acetylcholine receptor. The vast majority of the parvalbuminergic interneurons was immunoreactive for the alpha4 and the alpha7 nicotinic acetylcholine receptor. Provided these receptors would be functional--as suggested by recent electrophysiological findings--the connectivity pattern of cholinergic afferents appears much more complex than thought before. Not only direct cholinergic impact on cortical projection neurons but also the indirect modulation of these by cholinergic corticopetal fibers contacting intrinsic cortical cells would be possible.

Nucleus basalis Meynert lesions and the expression of nicotinic acetylcholine receptor proteins in the rat frontal cerebral cortex.

An important feature of cholinergic dysfunction in Alzheimer's disease (AD) is the degenerative loss of magnocellular cholinergic neurons in the basal nucleus of Meynert. In search for suitable animal models of Alzheimer dementia, rats with lesioned basal nuclei rats have been shown to display learning and memory disturbances. We here report on the quantitative assessment of the expression of the nicotinic acetylcholine receptor alpha4 protein in the rat frontal cerebral cortex following a unilateral lesion of the basal nucleus. Cortical alpha4 isoform expression shows a significant increase on the lesioned vs. the non-lesioned control side 1 week after lesioning. By contrast, no differences were observed 4 weeks after lesioning. In consideration of these results basal nucleus lesions appear as a questionable model of AD which in contrast to the present findings shows a decrease of cortical alpha4 nicotinic acetylcholine receptor protein expression.

Expression of nicotinic acetylcholine receptors in Alzheimer's disease: postmortem investigations and experimental approaches.

Nicotinic ligand binding studies have shown rather early that the cholinoceptive system is affected in Alzheimer's disease (AD). Today, molecular histochemistry enables one to study the nicotinic acetylcholine receptor (nAChR) subunit expression on the cellular level in human autopsy brains, in animal models and in in vitro approaches, thus deciphering the distribution of nAChRs and their role as potential therapeutic targets. The studies on the nAChR expression in the frontal and temporal cortex of AD patients and age-matched controls could demonstrate that both, the numbers of alpha4- and alpha7-immunoreactive neurons and the quantitative amount, in particular of the alpha4 protein, were markedly decreased in AD. Because the number of the corresponding mRNA expressing neurons was unchanged these findings point to a translational/posttranslational rather than a transcriptional event as an underlying cause. This assumption is supported by direct mutation screening of the CHRNA4 gene which showed no functionally important mutations. To get more insight into the underlying mechanisms, two model systems organotypic culture and primary hippocampal culture - have been established, both allowing to mimic nAChR expression in vitro. In ongoing studies the possible impact of beta-amyloid (Abeta) on nAChR expression is tested. Preliminary results obtained from primary cultures point to an impaired nAChR expression following Abeta exposure.

Quantitative assessment of nicotinic acetylcholine receptor proteins in the cerebral cortex of Alzheimer patients.

Cholinergic transmission has for long been known to be one of the most severely affected systems in Alzheimer's disease (AD), resulting clinically in massive cognitive deficits. The molecular basis of this dysfunction--on both the pre- and the postsynaptic sites--is still a matter of ongoing investigations. Here, we report on the quantitative assessment of nicotinic acetylcholine receptor isoform expression in AD vs. control cortices. For both subunit proteins assessed, the alpha4 and the alpha7 isoform, highly significant decreases in diseased vs. normal cortices were observed. Both alpha4 and alpha7 subunits are known to be important constituents in hetero- (alpha4beta2) and homooligomeric (alpha7) receptor subtypes. Their decreased expression may contribute to the decreased nicotinic binding known to be accompanied by AD and severe cognitive deficits. The quantitative assessment of nicotinic acetylcholine receptor expression will help to determine those subunits suited as targets for pharmacological stimulation.

Classical Alzheimer features and cholinergic dysfunction: towards a unifying hypothesis?

OBJECTIVE: Our autopsy studies show possible links between classical Alzheimer pathology and decreased expression of nicotinic acetylcholine receptors. For further elucidation we are now using in vitro models. We report preliminary evidence for the impact of beta-amyloid on nicotinic receptor expression in hippocampal dissociation culture. METHODS: Cultures (E18 rats) were grown in a serum-free medium and incubated at 8 days in vitro for 3 days with 1 microM Abeta1-42. Expression of alpha4, alpha7, and beta2 nicotinic receptor subunit protein was assessed immunohistochemically and rated semiquantitatively. RESULTS: Abeta1-42 incubation resulted in a massive reduction of alpha4 protein-expressing neurons, this effect was less pronounced for the alpha7 and beta2 subunit protein. CONCLUSION: These findings provide first evidence for a direct impact of classical Alzheimer pathology features on nicotinic receptor expression in vitro. Our model will be useful for testing the potential of drugs to stop or reverse these effects.

Mutation screening of the CHRNA4 and CHRNB2 nicotinic cholinergic receptor genes in Alzheimer's disease.

Potential genomic changes leading to decreased nicotine binding, crucial for cognitive dysfunction in Alzheimer's disease (AD), have not yet been studied. A search for mutations of the genes coding for the most widely distributed nicotinic receptor subtype alpha4beta2 (CHRNA4/CHRNB2) has been performed in AD patients by screening the coding regions of both genes by single strand conformation analysis and heteroduplex analysis of fibroblast-derived genomic DNA. Polymorphisms in CHRNA4, none of which led to amino acid changes in the predicted sequence, were found in three patients. Although the other receptor subunits have yet to be screened, it appears likely that the reduction of nicotine binding sites in AD is not due to genomic changes.

Expression of nicotinic acetylcholine receptor subunits in the cerebral cortex in Alzheimer's disease: histotopographical correlation with amyloid plaques and hyperphosphorylated-tau protein.

Impairment of cholinergic transmission and decreased numbers of nicotinic binding sites are well-known features accompanying the cognitive dysfunction seen in Alzheimer's disease (AD). In order to elucidate the underlying cause of this cholinoceptive dysfunction, the expression of two pharmacologically different nicotinic acetylcholine receptor (nAChR) subunits (alpha4, alpha7) was studied in the cerebral cortex of Alzheimer patients as compared to controls. Patch-clamp recordings of 14 dissociated neurons of control cortices showed responses suggesting the existence of alpha4- and alpha7-containing functional nAChRs in the human cortex. In cortices of Alzheimer patients and controls, the pattern of distribution and the number of alpha4 and alpha7 mRNA-expressing neurons were similar, whereas at the protein level a decrease in the density of alpha4- and alpha7-expressing neurons of approximately 30% was observed in Alzheimer patients. The histotopographical correlation of nAChR expression with accompanying pathological changes, e.g. accumulation of hyperphosphorylated-tau (HP-tau) protein and beta-amyloid showed that neurons in the vicinity of beta-amyloid plaques bore both nAChR transcripts. Neurons heavily labelled for HP-tau, however, expressed little or no alpha4 and alpha7 mRNA. These results point to an impaired synthesis of nAChRs on the protein level as a possible cause of the cholinoceptive deficit in AD. Further investigations need to elucidate whether interactions of HP-tau with nAChR mRNA, or alterations in the quality of alpha4 and alpha7 transcripts give rise to decreased protein expression at the level of individual neurons.

Occipitocervical fusion in patients with rheumatoid arthritis.

Instability and deformity of the cervical spine caused by rheumatoid arthritis is a well known entity. Operative intervention is indicated for patients with progressive deformity and when pain is resistant to conservative treatment. In a series of 39 patients who underwent posterior occipitocervical fusion with a Y plate, 22 patients were observed clinically and radiographically at average 41.5 months after surgery. In 35 of the 39 patients the main indication for surgery was pain, and in 30 of the 39 patients additional neurologic deficit (radiculopathy or myelopathy) was present. Thirty-one of the 39 patients had atlantoaxial instability. The atlantoaxial instability was associated with cranial migration of the dens in 19 patients. According to the classification of Conaty and Mongan 77.3% patients had satisfactory results and 22.7% had unsatisfactory results. Of the 30 patients with neurologic deficit, nine patients had a significant improvement. No patient had a worse result after surgery. Solid fusion was seen in all 22 patients at followup. Seven patients experienced complications directly related to the surgical procedure. Posterior fixation combined with anterior decompression in the presence of spinal stenosis represents a useful and safe method to treat instability and deformity caused by rheumatoid arthritis. Early surgical procedures may reduce the complication rate.

[Dorsal occipitocervical fusion--indications and results]. / Die dorsale occipitozervikale Fusion--Indikationen und Resultate.

STUDY DESIGN: This report will relate to our experience with the occipitocervical fusion with the y-plate, which we used in the treatment of 53 patients. METHODS: 39 of the patients had rheumatoid arthritis. Other indications demanding surgery were posttraumatic conditions, degenerative and congenital lesions, osteomyelitis, tumor and psoriasis arthritis. Before surgery, all patients suffered from pain in the neck and/or in the back of the head. On a linear scale from 0 to 10, the pain was rated as 8.0 in average (range 4 to 10). 33 patients had an instability of the atlantoaxial region and 26 patients a basilar invagination of the odontoid. A cervical myelopathy was found in 23 cases. One surgeon fused the occiput to C2 in 30 cases, to C3-C5 in 14 cases and to C7-T2 in 9 cases. In 17 patients a resection of the odontoid had to be performed before fusion to adequately decompress the spinal cord. RESULTS: 31 of the patients could be controlled with a follow-up of at average 45.9 months. 16 patients had died. At the time of follow-up, the pain was rated as 2.1 in average (range 0 to 8). The myelopathy cleared up in all cases but 3.9 patients required further operations on the cervical spine. 5 patients developed an instability at the level(s) below the fusion and an enlargement of the fusion to these levels had been performed. The fusion rate was 98.1%. The results were satisfying in 25 (80.6%) and not satisfying in 5 patients (19.4%). CONCLUSIONS: These results show the effectiveness of the occipitocervical fusion with the y-plate in a wide range of applications. It offers advantages above other techniques.

[Occipitocervical fusion in chronic polyarthritis]. / Die okzipitozervikale Fusion bei chronischer Polyarthritis.

This report will relate our experience with the y-plate, which we used in the treatment of 39 patients (32 women and 7 men) with a mean age of 62.6 years (range 47 to 79 years) between 1987 and 1994. All patients had rheumatoid arthritis. Occipitocervical fusion was indicated by instabilities within the occipitocervical region and in cases with additional basilar invagination and/or after transoral dens resection for decompression of the spinal cord. The length of the fusion depended on the pathological changes of the subaxial cervical spine. Before surgery, 35 patients suffered from strong and 4 patients from moderate pain in the neck and/or the back of the head. On a linear scale from 0 to 10, the pain was rated as 8:1 on average (range 4 to 10). 31 patients had an instability of the atlantoaxial region and 19 patients a basilar invagination of the odontoid. A cervical myelopathy was found in 20 cases. One surgeon fused the occiput to C2 in 22 cases, to C3-C5 in 8 cases and to C7-T2 in 9 cases. An important factor in this operation is the integration of atlantoaxial screws in order to resist the translational dislocation of C1/C2. In 13 patients a resection of the odontoid had to be performed to adequately decompress the spinal cord. A reduction of C2 without dens resection was performed in cases with reducible instability C1/2. 32 of the patients could be controlled with a minimum follow-up of 12 months (average 32.2 months, range 12 to 66 months). Out of the other 7, 6 patients had died. At the time of follow-up, the pain was rated as 2.3 on average (range 0 to 10). A myelopathy was present in 2 cases. Six patients required further operations on the cervical spine; 4 patients developed an instability at the level(s) below the fusion and an enlargement of the fusion to these levels has been performed. The fusion rate was 96.9%, despite breakage of the implant in 3 and a screw loosening in 2 patients. According to the criteria of Conaty, the result was satisfying in 25 (75%) and not satisfying in 8 patients (25%). These results show the effectiveness of the occipitocervical fusion with the y-plate in rheumatoid arthritis. A transoral dens resection is only indicated in cases with basilar invagination causing a compression of the spinal cord or in such cases where a compression caused by the dens or the retrodental pannus formation cannot be treated by a reduction of the second cervical vertebra alone.