Pyrocarbon versus cobalt-chromium in the context of spherical interposition implants: an in vitro study on cultured chondrocytes.

In the context of shoulder surgical replacement, a new generation of spherical interposition implants has been developed, with the implant being a mobile spacer rubbing against the glenoid cartilage and humeral bone cavity. The aim of the present study was to compare pyrocarbon (PyC) versus cobalt-chromium (CoCr) implants, regarding preservation and regeneration of the surrounding tissues. The effect of the biomaterials on chondrocytes was analysed in vitro. Murine primary chondrocytes were grown on discs made of PyC or CoCr using two culture media to mimic either cartilage-like or bone-like conditions (CLC or BLC). Chondrocytes did grow on PyC and CoCr without alteration in cell viability or manifestation of cytotoxicity. The tissue-like cell membranes grown under BLC were examined for the chondrocyte's ability to mineralise (by alizarin red matrix staining, calcium deposit and alkaline phosphatase activity) and for their mechanical properties (by rheological tests). For the chondrocytes grown under CLC and BLC, extracellular matrix components were analysed by histological staining and immunolabelling. Under CLC, PyC promoted type II collagen expression in chondrocytes, suggesting that they may generate a more cartilage-like matrix than samples grown on both CoCr and plastic control. In BLC, the tissue-like cell membranes grown on PyC were more mineralised and homogenous. The mechanical results corroborated the biological data, since the elastic modulus of the tissue-like cell membranes developed on the PyC surface was higher, indicating more stiffness. Overall, the results suggested that PyC might be a suitable biomaterial for spherical interposition implants.

The course of quality of life and neurocognition in newly diagnosed patients with glioblastoma.

BACKGROUND: The importance of QoL and neurocognitive functions in patients with glioblastoma (GB) is above controversy by now. We followed newly diagnosed GB patients treated with radio-chemotherapy during their course of disease by continuously evaluating their quality of life (QoL) and cognitive functions. METHODS: We included consecutive patients with newly diagnosed GB from 2010 to 2013 at the Medical University of Vienna. To assess QoL the EORTC QLQ C30 and BN20 questionnaire were used. Neurocognition was measured with the NeuroCog FX. The evaluations were done 6 times every three months, beginning at the beginning of radio-chemotherapy. RESULTS: 42 patients participated in this study. We also recorded QoL and neurocognition in 23 patients after the first disease progression. Patients maintained their cognitive summary score until relapse. Patients with left-sided tumors showed significant lower scores in the subscale verbal fluency than patients with right-sided tumors. The global health score of QoL decreased after the fifth evaluation (13months after diagnosis) whereas a peak of fatigue symptoms was obtained at the third evaluation. Furthermore, fatigue symptoms increased strongly 7months after diagnosis and patients' financial difficulties were mentioned more frequently by younger patients and in patients with lower education levels. CONCLUSIONS: QoL and cognitive long-term assessments are feasible also in some patients with GB after a symptomatic progression. Our study demonstrates maintenance of QoL and cognitive summary scales before tumor progression. Moreover, it highlights subgroups according to tumor location and socioeconomic factors.

Androgen receptor expression is associated with adverse pathological features in ureteral but not in pelvicalyceal urothelial carcinomas of the upper urinary tract.

PURPOSE: This study aims to determine the significance of androgen receptor (AR) expression in urothelial carcinoma of the upper urinary tract (UTUC). METHODS: AR expression was assessed on tissue microarrays containing specimens of 737 patients with UTUC who underwent radical nephroureterectomy with curative intent. AR expression was correlated with clinical and pathological tumor features as well as recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). RESULTS: Overall, AR was expressed in 11 % of tumors. AR expression was significantly associated with tumor necrosis as well as sessile and multifocal tumor growth but not with RFS, CSS or OS. AR was detected nearly twice as often in tumors of the ureter than of the pelvicalyceal system (p = 0.005). Subgroup analyses showed that the significant associations of AR with unfavorable pathologic features were exclusively attributable to tumors located in the ureter. However, in both ureteral and pelvicalyceal tumors, AR status was independent of RFS, CSS and OS. CONCLUSIONS: In this cohort of patients treated with RNU, AR expression was found in approximately 10 % of UTUCs, twice as often in ureteral than in pelvicalyceal tumors. While AR expression had no impact on postoperative prognosis, it was significantly associated with unfavorable pathologic features in ureteral tumors. Steroid hormone signaling might be relevant for future investigations of differences between ureteral and pelvicalyceal tumors.

Improvement of a dendritic cell-based tumour vaccine by an influenza virus.

BACKGROUND: Induction of cytotoxic T cells by dendritic cells (DCs) is a promising approach to tumour-immunotherapy. A standardized effective preparation of DCs remains a challenge for clinical application. MATERIAL AND METHODS: We assessed whether influenza A partial NS1 deletion (NS1-124) - or complete NS1 deletion (delNS1) vaccine viruses can be employed to enhance monocyte-derived dendritic cell (MODC)-based T-cell stimulation directed against malignant cells in vitro. RESULTS: Infection of cultures containing human MODCs and CD3(+) T cells with NS1 deletion viruses led to an increased induction of type I interferons and IL-6 compared with infection with wild-type virus. This correlated with the fact that infection of MODCs with NS1 deletion viruses but not with wild type virus led to stimulation of a cytotoxic T-cell (CTL) response against the Panc-1 cells, which were used as cell lysate to prime the MODCs. Moreover, stimulation of MODCs with Panc-1 tumour cell lysate obtained via lysis with the complete deletion virus delNS1, but not with the partial NS1 deletion virus also enhanced the CTL response against the tumour cells. Induction of function CTL response in those assays correlated with an increased proliferation of CD8(+) T cells. CONCLUSIONS: The pro-inflammatory capacity of influenza NS1 deletion vaccine viruses could serve as an adjuvant-like agent to improve preparations of MODC-based anti-cancer vaccines. The complete NS1 deletion virus appears to be more potent as adjuvant when used for production of tumour lysates.

Guidelines to the treatment of meningioma.

EPIDEMIOLOGY: Meningiomas constitute the largest subgroup of all intracranial tumours. Their incidence is about 2-3/100,000/yr, with a 3:2 to 2:1 female:male ratio, with a peak incidence in the sixth and the seventh decade of life. Meningiomas are usually slow growing, benign neoplasms, causing symptoms by compression of adjacent structures or by increased cranial pressure, the specific symptoms depending on the location of the tumour. RISK FACTORS: Meningiomas can be induced by radiation to the head, even by low dose radiation as used for dental radiographic examination after up to 35 yrs interval. The female preponderance in meningioma patients as well as the expression of progesterone receptor on the cell membranes of more than 50% of meningiomas is argument for an influence of gestagene in meningioma proliferation. The most frequent genetic predisposition of meningiomas is associated with neurofibromatosis 2 (NF-2); at least 40% of meningiomas show a deletion in the NF-2 gene. TREATMENT: To date, surgical resection is the mainstay of meningioma therapy. The completeness of the resection is the single most important prognostic factor for recurrence. In case of incomplete resection or recurrence, radiation therapy with 54 Gy (1.8 to 2 Gy/fraction) yields comparable results to total resection. Radiosurgery is a valuable alternative to radiotherapy (RT), maybe in the future also for surgery, as recently demonstrated. In the rare meningioma patients, that have exhausted the possibilities of surgery and RT, there have been some successful small series using hydroxyurea or interferon alpha. Future therapeutic options might consist in octreotide isotopic therapy or targeted therapy directed against tumour neo-angiogenesis or other proliferation associated markers in meningiomas.

The B-box dominates SAP-1-SRF interactions in the structure of the ternary complex.

The serum response element (SRE) is found in several immediate-early gene promoters. This DNA sequence is necessary and sufficient for rapid transcriptional induction of the human c-fos proto-oncogene in response to stimuli external to the cell. Full activation of the SRE requires the cooperative binding of a ternary complex factor (TCF) and serum response factor (SRF) to their specific DNA sites. The X-ray structure of the human SAP-1-SRF-SRE DNA ternary complex was determined (Protein Data Bank code 1hbx). It shows SAP-1 TCF bound to SRF through interactions between the SAP-1 B-box and SRF MADS domain in addition to contacts between their respective DNA-binding motifs. The SAP-1 B-box is part of a flexible linker of which 21 amino acids become ordered upon ternary complex formation. Comparison with a similar region from the yeast MATalpha2-MCM1-DNA complex suggests a common binding motif through which MADS-box proteins may interact with additional factors such as Fli-1.

Glial gene expression during aging in rat striatum and in long-term responses to 6-OHDA lesions.

The male rat striatum was examined for age-related changes in mRNAs expressed in astrocytes and microglia in two rat genotypes that differ by 35% in mean and maximum life spans: F344 and the longer-lived F1 (BN x F344) hybrid. The findings extend the established age-related increases in GFAP (glial fibrillary acidic protein) to other glial mRNAs: two lipoprotein mRNAs that are predominantly expressed in striatal astrocytes, apoE (apolipoprotein E) and apoJ (apolipoprotein J, clusterin, CLI, or SGP-2), and two mRNAs expressed in striatal microglia, TGF-beta1 and complement C1qB. By Northern blot hybridization, both genotypes showed progressive increases of GFAP mRNA to > 2.5-fold by the lifespan. Although the rat strains differed 35% in life span, the slope of the GFAP mRNA regression on age did not differ. Relative to GFAP, the increases of apoE, apoJ, C1q, and TGF-beta1 mRNAs were smaller, < or = 1.5-fold. Because prior studies showed that acute damage to striatal afferents induced astrocyte gene expression increases resembling those that also occur during aging, we examined long-term effects of damage to substantia nigra neurons on striatal astrocyte changes during aging. Young F344 rats were given 6-OHDA lesions that cause striatal dopamine deficits and induce GFAP. When examined 15 months later at age 18 months, there was no effect during prior lesions on the age-related elevation of GFAP mRNA. We conclude that aging changes in striatal GFAP mRNAs do not interact with loss of dopaminergic output to the striatum from 6-OHDA lesions and may be independent of the relatively modest dopaminergic losses during normal aging.

[Involvement of the central nervous system in hemolytic uremic syndrome/thrombotic thrombocytopenic purpura]. / Beteiligung des zentralen Nervensystemes bei hämolytischurämischem Syndrom/thrombotisch-thrombozytopenischer Purpura.

Cerebral involvement is typical for thrombotic microangiopathies like haemolytic uremic syndrome (HUS) and thrombotic-thrombopenic purpura (Moschcowitz disease or TTP). Symptoms are irritation, restless behaviour, disorientation, disturbance of consciousness, seizures, and focal neurological deficits. The lack of typical imaging changes or pathological observations may explain the unknown pathophysiological cascade leading to the neurological symptoms. We describe the development of HUS/ TTP in a 52-year-old woman after acute pneumonia caused by Diplococcus pneumoniae. The patient showed an increasing psycho-organic syndrome with disorientation, followed by severe loss of consciousness and coma. Initially, computed tomography showed slight diffuse brain oedema, which was not found in later follow-up images. Magnetic resonance imaging was normal. The TCD examination revealed general velocity increases and vasospasms (especially MCA, ACA and PCA bilateral and BA). The reduction in blood flow velocities in the basal arteries was accompanied by a marked clinical improvement. The development of vasospasms may be an explanation for the neurological deficits in HUS/TTP. The origin of the vasospasms may be found in disturbed prostacyclin production, increased serotonin or platelet factor IV release, and leucocyte activation with consecutive endothelial damage.

Functional brain organization, handedness, and immune vulnerability in musicians and non-musicians.

In the current investigation an approach has been made to explore possible relations between musical talent, left-handedness, anomalous dominance for verbal materials, and immune vulnerability. Fifty-one young adult musicians and non-musicians were tested with Wing's Standardized Tests of Musical Intelligence, with a handedness questionnaire, a dichotic listening task, and with a questionnaire assessing asthma/allergies, migraine and myopia. In addition, IgE, Ig total, beta-endorphin, testosterone, and estradiol were measured in blood serum. Musical talent was related to left-handedness and to anomalous dominance; immune vulnerability was found in female musicians, and in subjects with reversed dominance for language functions as well as in male left-handers, independently of musical talent.

Anomalous dominance, immune parameters, and spatial ability.

In a sample of male and female subjects in late adolescence, we investigated the relationship of spatial abilities to anomalous dominance and immune parameters as suggested by Geschwind's model of cerebral lateralization (Geschwind & Galaburda, 1985) In addition to the behavioral markers asthma/allergies, migraine, and myopia, we measured IgE and Ig total in blood serum. Atypical handedness, atypical language dominance, and atypical visuospatial dominance were found to be connected with spatial giftedness, and atypical handedness was related to immune vulnerability in males. This outcome provided some support for the Geschwind model in men. In women, spatial giftedness was related to immune vulnerability, but no indicator of anomalous dominance was connected with either giftedness, or immune parameters. Thus, the central thesis of the Geschwind model, i.e., elevated prenatal testosterone effects on the developing brain cause anomalous dominance and, as side effects, spatial giftedness and immune vulnerability, and all these consequences should be related to each other, was not confirmed by our data for females.

Testosterone, estradiol, ACTH and musical, spatial and verbal performance.

Testosterone, estradiol, and ACTH were determined in blood serum of 26 healthy males aged 19.16 and of 25 healthy females aged 18.77 years on average, and results were correlated with test scores of three spatial tests, a verbal fluency measure, and a test measuring general musical ability. In addition, hemispheric lateralization for verbal material and handedness was assessed. While testosterone and estradiol alone were not significantly related to any of the cognitive or musical tests, testosterone/estradiol ratio was significantly negatively correlated with spatial tests, and ACTH was significantly positively correlated with spatial and musical tests. Correlations were stronger in females than in males. The laterality index was significantly negatively correlated with testosterone in males indicating that right hemisphere involvement in verbal processing was associated with high testosterone levels.

Creative musical behavior and sex hormones: musical talent and spatial ability in the two sexes.

Creative musical behavior, musical intelligence, and spatial ability were investigated in relation to salivary testosterone (T). In a cross-sectional study with 117 adults and in an 8-yr longitudinal study with 120 adolescents, composers, instrumentalists, and nonmusicians of both sexes were compared by analyses of variance. Results indicate that an optimal T range may exist for the expression of creative musical behavior. This range may be at the bottom of normal male T range and at the top of normal female T range. In addition, musicians were found to attain significantly higher spatial test scores than nonmusicians, both, in an 8-yr-period of adolescent development and in adulthood.

Maturation rate and spatial, verbal, and musical abilities: a seven-year-longitudinal study.

We traced spatial, verbal and musical abilities through a seven-year period of adolescence. When we started our study, 60 boys had reached a mean age of 11.72, 60 girls were 11.52 on average. Menarche and mutation served as markers for maturation. We found that early, mid, and late maturers differed on spatial orientation and on tactile-visual discrimination as measured with the Witelson task. No differences between the maturational groups emerged on verbal fluency and on Wing's Standardized Tests of Musical Intelligence. At some stages, sex differences on spatial, verbal, and musical tests emerged, and disappeared at others. The sex differences in performance levels were not associated with a sex-specific relationship between maturation rate and performance levels. We found indications of the usefulness of sex hormone measurement in relation to cognitive and musical development in adolescence.

Testosterone and artistic talents.

Musical composers, instrumentalists, and painters were compared with nonmusicians from a student and from an nonstudent population on testosterone levels in saliva. This steroid served as a marker for physiological androgyny. The ANOVA showed a significant group by sex interaction. Male composers attained significantly lower mean testosterone values than male instrumentalists and male nonmusicians; female composers had significantly higher mean testosterone values than female instrumentalists and female nonmusicians. Painters of both sexes did not differ significantly from controls. Spatial ability was assessed in the five groups. Significant differences on spatial test performance were not reflected in differences on salivary testosterone. Our results showed that musical composers of both sexes were physiologically highly androgynous. Creative musical behavior was associated with testosterone levels that minimized sex differences.

Testosterone and musical talent.

Two recently published hypotheses on the biological basis of special talents are discussed in relation to experimental data obtained from musical composers, instrumentalists, painters, and non-musicians, and from adolescent boys and girls with different levels of musical capacities. Both hypotheses assign an important influence to prenatal testosterone effects on the developing brain. Geschwind and Galaburda (1985) predict that subjects with special talents may have anomalous hemispheric dominance for verbal material. This was confirmed experimentally in adolescents and in adults using a dichotic listening task to assess functional lateralization. Hassler and Nieschlag (1989) expect musicians of both sexes to be psychologically androgynous and to have current testosterone levels that differ from sex-typed males and females. Salivary testosterone was measured in adults and in adolescents. Creative musical behavior was associated with very low testosterone values in males, and with high testosterone levels in females. Sexual activity level and motivation did not differ between males with testosterone levels less than or equal to 200 pmol/l and those with greater than 220 pmol/l. We tentatively suggest from our data that, among a complex interaction of biological and social factors, an optimal testosterone range may exist for the expression of creative musical behavior. Exceeding the range in the course of adolescence may be detrimental for musical creativity in boys.

Functional cerebral asymmetries and cognitive abilities in musicians, painters, and controls.

The relative participation of left- and right-hemisphere functions in verbal and spatial processing with musical composers, instrumentalists, painters, and non-musicians from student and junior high school populations was investigated. Hemispheric lateralization was related to the outcome of tests measuring spatial orientation, spatial visualization, tactile-visual discrimination, and verbal fluency. The relationship between lateral dominance and cognitive variables was influenced by sex and musical talents and the ability to paint. Males, irrespective of talents, were lateralized stronger than females. These sex differences were due to nonmusicians, only. Male and female composers, instrumentalists, and painters did not differ in language lateralization. Female left-handers showed a marked tendency for reversed language lateralization; left-handed males did not.

Masculinity, femininity, and musical composition psychological and psychoendocrinological aspects of musical and spatial faculties.

Physiological and psychological masculinity and femininity were assessed in relation to musical capacities and spatial ability. Male composers had lower mean testosterone levels than male instrumentalists and male non-musicians; female composers had higher testosterone levels than female instrumentalists and female non-musicians. Testosterone in saliva was the physiological marker for androgyny. All of the groups were found to be psychologically androgynous on Bem's Sex-Role Inventory and all groups had above average spatial ability. Musicians, however, surpassed non-musicians on spatial visualization and on Witelson's Dichaptic Stimulation Test.

[MRI of the cervical spine. Creation of a surface coil. Technical and clinical results]. / IRM du rachis cervical. Réalisation d'une antenne de surface. Résultats techniques et cliniques.

Cervical myelopathy represents a good indication for study by Magnetic Resonance Imaging (MRI). The MRI examination may be performed without hospitalisation and without any pain or risk for the patient. It often gives sufficient information to decide whether to proceed with surgical intervention, after imaging on standard plain films and ever before cervical myelography. An efficient study of the cervical spinal cord requires special surface coils adapted to this region. We have developed a surface coil, working as a receiver, inductively coupled, tuned and matched all at once, and easy to use. The concave form of this coil has been studied so as to be comfortable for all patients. It can be directly connected to our Thomson CGR machines (Magniscan 5000). In continuous routine use for 6 months, without any problems, it has been found to be very reliable. We present here some results on different types of myelopathy and discuss methodological aspects concerning the choice of acquisition parameters in the examinations. The simplicity of its realisation and the low cost leads us to believe that it will be possible to construct other surface coils convenient on many other parts of the body.