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Eye movements are generated by different premotor pathways. Damage to them can cause specific deficits of eye movements, such as saccades. For correlative clinico-anatomical post-mortem studies of cases with eye movement disorders it is essential to identify the functional cell groups of the oculomotor system in the human brain by marker proteins. Based on monkey studies, the premotor neurons of the saccadic system can be identified by the histochemical markers parvalbumin (PAV) and perineuronal nets in humans. These areas involve the interstitial nucleus of Cajal (INC) and the rostral interstitial nucleus of the medial longitudinal fascicle (RIMLF), which both contain premotor neurons for upgaze and downgaze. Recent monkey and human studies revealed a selective excitatory calretinin (CR)-positive input to the motoneurons mediating upgaze, but not to those for downgaze. Three premotor regions were identified as sources of CR input in monkey: y-group, INC and RIMLF. These findings suggest that the expression pattern of parvalbumin and CR may help to identify premotor neurons involved in up- or downgaze. In a post-mortem study of five human cases without neurological diseases we investigated the y-group, INC and RIMLF for the presence of parvalbumin and CR positive neurons including their co-expression. Adjacent thin paraffin sections were stained for the aggrecan (ACAN) component of perineuronal nets, parvalbumin or CR and glutamate decarboxylase. The comparative analysis of scanned thin sections of INC and RIMLF revealed medium-sized parvalbumin positive neurons with and without CR coexpression, which were intermingled. The parvalbumin/CR positive neurons in both nuclei are considered as excitatory premotor upgaze neurons. Accordingly, the parvalbumin-positive neurons lacking CR are considered as premotor downgaze neurons in RIMLF, but may in addition include inhibitory premotor upgaze neurons in the INC as indicated by co-expression of glutamate decarboxylase in a subpopulation. CR-positive neurons ensheathed by perineuronal nets in the human y-group are considered as the homolog premotor neurons described in monkey, projecting to superior rectus (SR) and inferior oblique (IO) motoneurons. In conclusion, combined immunostaining for parvalbumin, perineuronal nets and CR may well be suited for the specific identification and subsequent analysis of premotor upgaze pathways in clinical cases of isolated up- or downgaze deficits.

Targeted high-throughput sequencing of many amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD) genes in parallel has the potential to reveal novel ALS- and/or FTD-phenotypes and to provide missing links on the ALS-FTD continuum. For example, although the 43-kDa transactive response DNA binding protein is the major pathologic hallmark linking ALS and FTD, mutations in the gene encoding 43-kDa transactive response DNA binding protein (TARDBP) have been appreciated only as a cause of ALS-phenotypes, but not yet of pure FTD. Thus, the genetic link is not yet well substantiated that TARDBP mutations can cause the full spectrum of the ALS-FTD continuum. High-throughput sequencing of 18 ALS and FTD genes in an index patient presenting with early-onset pure (behavioral) FTD and a positive family history for ALS revealed an established TARDBP mutation, A382T. This finding demonstrates that a TARDPB mutation can cause early-onset pure FTD without evidence for ALS even in advanced FTD disease stages. Moreover, it indicates that TARDPB screening might be considered even in young patients with "pure" neuropsychiatric disturbances and without evidence of neurodegenerative disease in the parental generation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Loss of meniscal tissue is correlated with early osteoarthritis but few data exist regarding detailed biomechanical properties (e.g. viscoelastic behavior) of menisci in different species commonly used as animal models. The purpose of the current study was to biomechanically characterize bovine, ovine, and porcine menisci (each n = 6, midpart of the medial meniscus) and compare their properties to that of normal and degenerated human menisci (n = 6) and two commercially available artificial scaffolds (each n = 3)., Methods: Samples were tested in a cyclic, minimally constraint compression-relaxation test with a universal testing machine allowing the characterization of the viscoelastic properties including stiffness, residual force and relative sample compression. T-tests were used to compare the biomechanical parameters of all samples. Significance level was set at p < 0.05., Results: Throughout cyclic testing stiffness, residual force and relative sample compression increased significantly (p < 0.05) in all tested meniscus samples. From the tested animal meniscus samples the ovine menisci showed the highest biomechanical similarity to human menisci in terms of stiffness (human: 8.54 N/mm ± 1.87, cycle 1; ovine: 11.24 N/mm ± 2.36, cycle 1, p = 0.0528), residual force (human: 2.99 N ± 0.63, cycle 1 vs. ovine 3.24 N ± 0.13, cycle 1, p = 0.364) and relative sample compression (human 19.92% ± 0.63, cycle 1 vs. 18.72% ± 1.84 in ovine samples at cycle 1, p = 0.162). The artificial constructs -as hypothesized- revealed statistically significant inferior biomechanical properties., Conclusions: For future research the use of ovine meniscus would be desirable showing the highest biomechanical similarities to human meniscus tissue. The significantly different biomechanical properties of the artificial scaffolds highlight the necessity of cellular ingrowth and formation of extracellular matrix to gain viscoelastic properties. As a consequence, a period of unloading (at least partial weight bearing) is necessary, until the remodeling process in the scaffold is sufficient to withstand forces during weight bearing.

Background: The pathophysiological basis of reversible cerebral vasoconstriction syndrome is poorly understood but carotid artery dissection has been discussed as a rare possible cause. So far, only single cases of unilateral carotid artery dissection and reversible cerebral vasoconstriction syndrome have been reported., Case: Here, we describe the case of a 54-year old patient presenting to the emergency department with right hemiparesis, hypaesthesia and dysarthria. Furthermore, he reported two episodes of thunderclap headache after autosexual activity. Cerebral imaging showed ischaemic infarcts, slight cortical subarachnoid haemorrhage, bilateral carotid artery dissection and fluctuating intracranial vessel irregularities, compatible with reversible cerebral vasoconstriction syndrome. An extensive diagnostic work-up was normal. No typical trigger factors of reversible cerebral vasoconstriction syndrome could be found. The patient received intravenous heparin and the calcium channel blocker nimodipine. Follow-up imaging revealed no vessel irregularities, the left internal carotid artery was still occluded., Conclusion: This case supports the assumption that carotid artery dissection should be considered as a potential trigger of reversible cerebral vasoconstriction syndrome, possibly by altering sympathetic vascular tone.

The acellularization of tendons using detergents (sodium dodecyl sulfate, Triton-X, tri-nitro-butyl-phosphate) is a new source of scaffolds for tissue engineering in anterior cruciate ligament (ACL) repair. In vitro testing demonstrated that acellular tendon scaffolds are biocompatible and show good biomechanical properties, but in vivo confirmation of these results is not yet available. Therefore, the aim of this study was to see in vivo if an acellular allogenic construct colonized with autologous fibroblasts improves the quality of ACL reconstruction. ACL replacement was performed in 31 New Zealand White rabbits using a standardized model. Fifteen animals received autologous semitendinosus tendon, whereas 16 animals were treated with a tissue-engineered construct. This construct was made by acellularization of allogenic semitendinosus tendons using sodium dodecyl sulfate and subsequent in vitro colonization with autologous fibroblasts. Eight weeks postoperatively, macroscopic, biomechanical (ultimate load to failure, elongation, stiffness; n = 8/9), and histological (n = 5) examinations were performed. Biomechanical testing showed decreasing strength of the constructs at 8 weeks after implantation compared with the direct postsurgical strength. However, tissue-engineered constructs (F = 19.7 +/- 20.3 N) were significantly weaker than autologous tendons (F = 61.2 +/- 31.2 N). Histologically, the autologous tendons showed signs of partial necrosis and tissue remodeling. The tissue-engineered constructs exhibited an inflammatory reaction and showed both repopulated and acellular regions. In conclusion, in vivo results were much more unfavorable than in vitro results had suggested. Further studies have to be performed to test if modifications of the acellularization process yield better results in vivo.

Meniscus tears are frequent indications for arthroscopic evaluation which can result in partial or total meniscectomy. Allografts or synthetic meniscus scaffolds have been used with varying success to prevent early degenerative joint disease in these cases. Problems related to reduced initial and long-term stability, as well as immunological reactions prevent widespread clinical use so far. Therefore, the aim of this study was to develop a new construct for tissue engineering of the human meniscus based on an acellular meniscus allograft. Human menisci (n = 16) were collected and acellularized using the detergent sodium dodecyl sulfate as the main ingredient or left untreated as control group. These acellularized menisci were characterized biomechanically using a repetitive ball indentation test (Stiffness N/mm, residual force N, relative compression force N) and by histological (hematoxylin-eosin, phase-contrast) as well as immunohistochemical (collagen I, II, VI) investigation. The processed menisci histologically appeared cell-free and had biomechanical properties similar to the intact meniscus samples (p > 0.05). The collagen fiber arrangement was not altered, according to phase-contrast microscopy and immunohistochemical labeling. The removal of the immunogenic cell components combined with the preservation of the mechanically relevant parts of the extracellular matrix could make these scaffolds ideal implants for future tissue engineering of the meniscus., ((c) 2008 Wiley Periodicals, Inc.)

How do students use multimedia tools to support their learning during a gross anatomy dissection course? We investigated this question in the anatomic dissection course for first year medical students at the University of Munich (n=850) by giving all participating students access to an anatomical multimedia CD-ROM. The use of this multimedia learning tool was voluntary and it was not essential for the end-of-course examination. After the examination, two questionnaires (return rate first questionnaire n(1)=347, approximately 41%; return rate second questionnaire n(2)=644, approximately 76%) were given to the surveyed students with the following content: evaluation of the multimedia learning tool, details about the usage of different kinds of available learning media, and finally an evaluation of the media used for teaching during the course. Furthermore we collected personal data from participants such as age, gender and the score achieved in the examination. Classical textbooks and anatomical atlases were used by 84% of students for preparation. The multimedia learning tool was used by 34% as an additional media for learning. The multimedia learning tool was not used alone. The data showed differences with regard to gender and performance of students, but not relating to age. Students rated the computer-specific features, e.g. three-dimensional (3D) models, virtual simulations, and an interactive quiz module, as major reasons for using the multimedia learning tool. Our results show that medical students use anatomic multimedia learning tools primarily as an additional medium for learning, and thus lead to the conclusion that the main learning media are still textbooks and anatomic atlases.

Introduction: The availability of autogenous tendons (middle part of patellar tendon, semitendinosus/gracilis, or quadriceps tendon) for cruciate ligament reconstructions is restricted and related to withdrawal morbidity. Allografts and synthetic ligament materials often show problems regarding long-term stability and immunological reactions. Therefore, the aim of this study was to develop and characterize a new scaffold based on acellular allografts seeded with autologous cells for tissue engineering of the anterior cruciate ligament (ACL)., Materials and Methods: Semitendinosus tendons of New Zealand White (NZW) rabbits were harvested and acellularized using the detergent sodium dodecyle sulfate (SDS) as the main ingredient. After that, cultured (37 degrees C, 5% CO(2), medium) dermal fibroblasts were injected into the tendons. These constructs were further cultivated for 4, 7, or 14 days under the same culture conditions. Native, acellular, and seeded tendons underwent biomechanical testing (ultimate load to failure [N], stiffness [N/mm], and elongation [%], each n = 9] and histological hematoxylin-eosin (H.E.) staining. Detailed immunohistochemical (collagen I, III, IV, VI, pro-collagen I, versican, and vimentin) analyses were conducted to detect changes in the composition and structure of the extracellular matrix (ECM) after acellularization., Results: Histologically, a cell-free, crimped slack tendon structure after acellularization and a good integration of the cells after injection (4, 7, and 14 days) were seen. Metabolic activity of the seeded cells was demonstrated by positive immunohistochemical staining for pro-collagen I, which was negative in nonseeded constructs. Major differences in staining patterns of the various other ECM components were not observed. Biomechanically, the maximum load to failure of these tendons was comparable to native tendons (P = 0.429; native 134.5 +/- 12.9 N; acellular 118.5 +/- 7.3 N; seeded 132.3 +/- 5.6 N). Stiffness and elongation were comparable between native and acellular tendons, but differed significantly after seeding (P < 0.001)., Conclusion: The described method is suitable to make tendons completely cell free without changing their major biomechanical properties. Preservation of the ECM and of the collagen fiber structure by this method should give an ideal environment for autologous cell integration and metabolic activity in contrast to other approaches for tissue acellularization. The cell disruption and extraction of cell detritus should minimize adverse immunogenic reactions.

Background: Placenta previa percreta with invasion of the broad ligament and uterine cervix is an extremely rare condition and carries high maternal and fetal morbidity and mortality., Case: A 39-year-old, multiparous woman with two previous cesarean sections presented in active labor at term with placenta previa percreta involving the left broad ligament and cervix. The patient was managed by antepartum diagnosis of placenta previa accreta, supracervical hysterectomy, and blood transfusion., Conclusion: This case was managed consistent with the literature, and favorable maternal and fetal outcomes were achieved.

Objective: To study the association between various fetal congenital malformations and the biophysical profile (BPP), we tested the following hypotheses: (1) a specific organ system malformation is associated with the absence of one or more BPP parameters, and (2) four BPP parameters are not affected by the advancement of fetal maturation., Study Design: From 1985 to 1995, 316 fetuses with congenital malformations and 351 controls were identified in a high-risk population undergoing ultrasound examinations of anatomic structures and biophysical profile evaluations. For investigation of the influence of fetal maturity on biophysical profile evaluations, both the malformed fetuses and the controls were stratified into two gestational-age groups, 26-34 weeks and > 34 completed weeks. Four parameters of the BPP, including (1) fetal breathing, (2) gross fetal movements, (3) fetal muscle tone, and (4) quantitative amniotic fluid volume, were divided into low (0-6) and high (8) total score subgroups. Tests of significance were done using chi 2 analysis, Student's t test or Fisher's exact test, as appropriate. Level of significance was set at P < .05., Results: When comparing malformed fetuses to controls, the malformed group had a statistically significantly higher percentage of low BPP scores due to absent fluid, tone or breathing. Fetuses with a musculoskeletal anomaly were statistically significantly more likely to lose points for fetal movement (P < .02); fetuses with a genitourinary system anomaly lost points for fluid (P < .001), tone (P < .005) and breathing (P < .005); fetuses with a central nervous system anomaly lost points for tone (P < .02) and breathing (P < .001); and fetuses with a thoracic anomaly lost points for breathing (P < .002). There was no statistically significant difference in BPP scores between fetuses at 26-34 weeks' gestational age and fetuses > 34 completed weeks' gestational age., Conclusion: The two hypotheses were confirmed by the study results.

Yeast cells were irradiated with 3.5 MeV alpha-particles and 30 MeV electrons, as reference radiation. The kinetics of DNA double-strand break (dsb) rejoining during incubation of cells under non-growth conditions (PLDR conditions) were measured using the neutral sedimentation technique. A monophasic kinetic was found after irradiation of cells with alpha-particles, with a dose-independent t1/2 value of about 13 h. The kinetics of rejoining of dsb induced by 30 MeV electrons was found to be biphasic, with dose-independent t1/2 values of 3.8 h for the initial and of about 11 h for the slow component. The fraction of the slow component was, however, dose-dependent. These kinetics were measured for both types of radiation at doses yielding high surviving fractions (5% up to 100%). Dsb are induced linearly with dose of both radiations. The RBE value of alpha-particles was found to be 2.5 for initial dsb. The RBE of alpha-particles increased as a consequence of dsb rejoining. This increase in RBE value suggests that DSB may be primary lesions for chromosome aberrations, cellular inactivation and oncogenic transformation of mammalian cells which all exhibit high RBE values of alpha-particles.