Myocardial injection of skeletal myoblasts impairs contractility of host cardiomyocytes

BACKGROUND: Mechanisms underlying improvement of myocardial contractile function after cell therapy as well as arrhythmic side effect remain poorly understood. We hypothesised that cell therapy might affect the mechanical properties of isolated host cardiomyocytes. METHODS: Two weeks after myocardial infarction (MI), rats were treated by intramyocardial myoblast injection (SkM, n=8), intramyocardial vehicle injection (Medium, n=6), or sham operation (Sham, n=7). Cardiac function was assessed by echocardiography. Cardiomyocytes were isolated in a modified Langendorff perfusion system, their contraction was measured by video-based inter-sarcomeric analysis. Data were compared with a control-group without myocardial infarction (Control, n=5). RESULTS: Three weeks post-treatment, ejection fraction (EF) further deteriorated in vehicle-injected and non-injected rats (respectively 40.7+/-11.4% to 33+/-5.5% and 41.8+/-8% to 33.5+/-8.3%), but was stabilised in SkM group (35.9+/-6% to 36.4+/-9.7%). Significant cell hypertrophy induced by MI was maintained after cell therapy. Single cell contraction (dL/dt(max)) decreased in SkM and vehicle groups compared to non-injected group as well as cell shortening and relaxation (dL/dt(min)) in vehicle group. A significantly increased predisposition for alternation of strong and weak contractions was observed in isolated cardiomyocytes of the SkM group. CONCLUSION: Our study provides the first evidence that injection of materials into the myocardium alters host cardiomyocytes contractile function independently of the global beneficial effect of the heart function. These findings may be important in understanding possible adverse effects.

Ranibizumab (Lucentis) in neovascular age-related macular degeneration: evidence from clinical trials

BACKGROUND: Neovascular age-related macular degeneration (AMD) has a poor prognosis if left untreated, frequently resulting in legal blindness. Ranibizumab is approved for treating neovascular AMD. However, further guidance is needed to assist ophthalmologists in clinical practice to optimise treatment outcomes. METHODS: An international retina expert panel assessed evidence available from prospective, multicentre studies evaluating different ranibizumab treatment schedules (ANCHOR, MARINA, PIER, SAILOR, SUSTAIN and EXCITE) and a literature search to generate evidence-based and consensus recommendations for treatment indication and assessment, retreatment and monitoring. RESULTS: Ranibizumab is indicated for choroidal neovascular lesions with active disease, the clinical parameters of which are outlined. Treatment initiation with three consecutive monthly injections, followed by continued monthly injections, has provided the best visual-acuity outcomes in pivotal clinical trials. If continued monthly injections are not feasible after initiation, a flexible strategy appears viable, with monthly monitoring of lesion activity recommended. Initiation regimens of fewer than three injections have not been assessed. Continuous careful monitoring with flexible retreatment may help avoid vision loss recurring. Standardised biomarkers need to be determined. CONCLUSION: Evidence-based guidelines will help to optimise treatment outcomes with ranibizumab in neovascular AMD.

Ringier (Familie)

Famille de pasteurs, politiciens et entrepreneurs de Zofingue, attestée pour la première fois en 1527, lorsque leur aïeul Jean, tonnelier originaire de Nîmes, obtint la bourgeoisie de Zofingue. Michael (1521-1605), avoyer, l'un de ses cinq fils, est l'ancêtre de la branche des imprimeurs et éditeurs. Après lui, de nombreux R. consolidèrent durablement l'influence de la famille. A partir du XVIIIe s., divers membres firent des carrières politiques, tels Samuel (1706-1786), avoyer, et Rudolf Friedrich (1805-1886), président de la ville. Les R. furent aussi très liés à l'Eglise. Le fils de Michael, Moritz (1557-1615), fut pasteur et doyen à Zofingue. Jusqu'au XIXe s., la famille compta une trentaine d'ecclésiastiques, essentiellement des pasteurs officiant sur le territoire bernois, tels Johann Heinrich ( -> 3) et Michael ( -> 8). Les conseillers Beat (1712-1778) et Niklaus (1734-1766) furent les premiers R. actifs dans la production protoindustrielle de drap. D'autres négociants suivirent jusqu'au milieu du XIXe s. L'architecte Niklaus Emanuel (1744-1815) construisit l'hôtel de ville de Zofingue (1792-1795) de style baroque tardif. Johann Rudolf ( -> 4) se distingua sous la République helvétique (1798-1803). Samuel (1767-1826), conseiller municipal de Zofingue, créa les armoiries du canton d'Argovie en 1803. Les R. s'affirmèrent sur le plan cantonal avec Karl Ludwig ( -> 6), chancelier, et Arnold ( -> 1), conseiller d'Etat et plusieurs fois landamman, et sur le plan fédéral avec Johann Rudolf ( -> 5), conseiller national, et Gottlieb ( -> 2), conseiller aux Etats et chancelier de la Confédération. Johann Rudolf (1803-1874) fonda, en 1833, l'imprimerie Ringier à Zofingue, reprise par son fils Franz Emil (1837-1898). A partir de 1898, Paul August ( -> 9), représentant de la troisième génération d'imprimeurs, agrandit l'entreprise dont il fit la principale imprimerie et maison d'édition de Suisse. Cette expansion se poursuivit après 1960 sous son fils Hans (1906-2003). Avec les fils de celui-ci, Christoph (naissance1941, dans la firme jusqu'en 1991) et Michael (naissance1949), Ringier devint, à partir de 1985, une entreprise multinationale et multimédia. Bibliographie – F. Schoder, Ortsbürger von Zofingen, 1962 – P. Meier, T. Häussler, Zwischen Masse, Markt und Macht, 2009

Ringier, Paul August

* naissance 18.6.1876 à Zofingue,décès 15.10.1960 à Zofingue, prot., de Zofingue. Fils de Johann Franz Emil, imprimeur, et d'Elisabeth Caroline Steiner. ∞ 1) Ida Brack, 2) Emmy Mathys. Apprentissage d'imprimeur. R. reprit la petite entreprise de son père en 1898. Il en fit la principale imprimerie et maison d'édition de Suisse en adoptant et développant le procédé de l'héliogravure. R. édita de nombreuses revues et journaux, dont la Schweizer Illustrierte Zeitung dès 1911 (Schweizer Illustrierte depuis 1965), L'Illustré à partir de 1921 et le Blick dès 1959. Bibliographie – B. Meier, T. Häussler, Zwischen Masse, Markt und Macht, 2009

Ringier (Unternehmen)

Gruppo mediatico di proprietà della fam. omonima, le cui origini risalgono alla tipografia fondata nel 1833 a Zofingen da Johann Rudolf (1803-1874). Nel 1898 Paul August Ringier, esponente della terza generazione, rilevò l'azienda, che ampliò fino a farne un'impresa tipografica industriale e una delle principali case editrici della Svizzera. Nel 1932 la Ringier fu trasformata in un gruppo, divenne una soc. anonima e fu fondata la holding. Fino al 1938 pubblicò nove riviste illustrate per fam., di intrattenimento e dedicate ai programmi radiofonici, con una tiratura complessiva di 680'000 copie; nel 1959 diede vita al Blick. Dal 1960 con Hans (1906-2003), figlio di Paul August, e dal 1985 con i suoi figli Christoph (nascita 1941; in azienda fino al 1991) e Michael (nascita 1949), l'impresa divenne il più grande gruppo mediatico della Svizzera. Dal 1980 si è espansa in Germania, Asia e negli Stati Uniti e dal 1992 nell'Europa orientale. Nel 2008 impiegava in tutto il mondo 8129 persone e la cifra d'affari ammontava a oltre 1,535 miliardi di frs. Bibliografia – P. Meier, T. Häussler, Zwischen Masse, Markt und Macht, 2009

FRAX® assessment of osteoporotic fracture probability in Switzerland

A Swiss-specific FRAX model was developed. Patient profiles at increased probability of fracture beyond currently accepted reimbursement thresholds for bone mineral density (BMD) measurement by dual X-ray absorptiometry (DXA), and osteoporosis treatment were identified.

The use of flat panel angioCT (DynaCT) for navigation through a deformed and fractured carotid stent

Navigation through a previously deployed and deformed stent is a difficult interventional task. Inadvertent navigation through the struts of a stent can potentially lead to incomplete secondary stent extension and vessel occlusion. Better visualisation of the pathway through the stent can reduce the risks of the procedural complications and reduce the reluctance of the interventionalist to navigate through a previously deployed stent. We describe a technique of visualisation of the pathway navigated by a guidewire through a previously deployed deformed and fractured carotid stent by the use of DynaCT. Three-dimensional reconstruction of the stent/microwire allows excellent visualisation of the correct pathway of the microwire within the stent.

Neuropeptide Y modulates steroid production of human adrenal H295R cells through Y1 receptors

Neuropeptide Y (NPY) is abundantly expressed in the nervous system and acts on target cells through NPY receptors. The human adrenal cortex and adrenal tumors express NPY receptor subtype Y1, but its function is unknown. We studied Y1-mediated signaling, steroidogenesis and cell proliferation in human adrenal NCI-H295R cells. Radioactive ligand binding studies showed that H295R cells express Y1 receptor specifically. NPY treatment of H295R cells stimulated the MEK/ERK1/2 pathway, confirming that H295R cells express functional Y1 receptors. Studies of the effect of NPY and related peptide PYY on adrenal steroidogenesis revealed a decrease in 11-deoxycortisol production. RIA measurements of cortisol from cell culture medium confirmed this finding. Co-treatment with the Y1 antagonist BIBP2336 reversed the inhibitory effect of NPY on cortisol production proving specificity of this effect. At mRNA level, NPY decreased HSD3B2 and CYP21A2 expression. However NPY revealed no effect on cell proliferation. Our data show that NPY can directly regulate human adrenal cortisol production.

CCK2 receptor splice variant with intron 4 retention in human gastrointestinal and lung tumours

The wild-type cholecystokinin type 2 (CCK(2)) receptor is expressed in many gastrointestinal and lung tumours. A splice variant of the CCK(2) receptor with retention of intron 4 (CCK(2)Ri4sv) showing constitutive activity associated with increased tumour growth was described in few colorectal, pancreatic and gastric cancers. Given the potential functional and clinical importance of this spliceoform, its occurrence was quantitatively characterized in a broad collection of 81 gastrointestinal and lung tumours, including insulinomas, ileal carcinoids, gastrointestinal stromal tumours (GIST), gastric, colorectal and pancreatic ductal adenocarcinomas, cholangiocellular and hepatocellular carcinomas, small cell lung cancers (SCLC), non-SCLC (nSCLC) and bronchopulmonary carcinoids, as well as 21 samples of corresponding normal tissues. These samples were assessed for transcript expression of total CCK(2) receptor, wild-type CCK(2) receptor and CCK(2)Ri4sv with end-point and real-time RT-PCR, and for total CCK(2) receptor protein expression on the basis of receptor binding with in vitro receptor autoradiography. Wild-type CCK(2) receptor transcripts were found in the vast majority of tumours and normal tissues. CCK(2)Ri4sv mRNA expression was present predominantly in insulinomas (incidence 100%), GIST (100%) and SCLC (67%), but rarely in pancreatic, colorectal and gastric carcinomas and nSCLC. It was not found in wild-type CCK(2) receptor negative tumours or any normal tissues tested. CCK(2)Ri4sv transcript levels in individual tumours were low, ranging from 0.02% to 0.14% of total CCK(2) receptor transcripts. In conclusion, the CCK(2)Ri4sv is a marker of specific gastrointestinal and lung tumours. With its high selectivity for and high incidence in SCLC and GIST, it may represent an attractive clinical target.

Refractory Hematuria in an Oliguric Patient After Pancreas Transplantation with Exocrine Pancreas Bladder Drainage

A 52-yr-old man presented with hematuria and clot retention. He had undergone simultaneous pancreas-kidney transplantation with exocrine pancreas bladder drainage 16 yr ago. The patient suffered from progressive transplant kidney failure with gradually decreasing urine output and needed hemodialysis every other day. Gross hematuria persisted after removal of all blood clots. Cystoscopy showed multiple small, flat ulcers of the bladder mucosa. Some bled discretely and were coagulated cautiously. However, hematuria was refractory to multiple urological interventions, which eventually necessitated an enteric diversion of the exocrine pancreas. Hematuria ceased following an uneventful postoperative course.

In Vitro and In Vivo Validation of Human and Goat Chondrocyte Labeling by Green Fluorescent Protein Lentivirus Transduction

We investigated whether human articular chondrocytes can be labeled efficiently and for long-term with a green fluorescent protein (GFP) lentivirus and whether the viral transduction would influence cell proliferation and tissue-forming capacity. The method was then applied to track goat articular chondrocytes after autologous implantation in cartilage defects. Expression of GFP in transduced chondrocytes was detected cytofluorimetrically and immunohistochemically. Chondrogenic capacity of chondrocytes was assessed by Safranin-O staining, immunostaining for type II collagen, and glycosaminoglycan content. Human articular chondrocytes were efficiently transduced with GFP lentivirus (73.4 +/- 0.5% at passage 1) and maintained the expression of GFP up to 22 weeks of in vitro culture after transduction. Upon implantation in nude mice, 12 weeks after transduction, the percentage of labeled cells (73.6 +/- 3.3%) was similar to the initial one. Importantly, viral transduction of chondrocytes did not affect the cell proliferation rate, chondrogenic differentiation, or tissue-forming capacity, either in vitro or in vivo. Goat articular chondrocytes were also efficiently transduced with GFP lentivirus (78.3 +/- 3.2%) and maintained the expression of GFP in the reparative tissue after orthotopic implantation. This study demonstrates the feasibility of efficient and relatively long-term labeling of human chondrocytes for co-culture on integration studies, and indicates the potential of this stable labeling technique for tracking animal chondrocytes for in cartilage repair studies.

Sellar collision tumor involving pituitary gonadotroph adenoma and chondroma: a potential clinical diagnosis

We report on a 74-year-old male patient who presented with progressive neuroophthalmologic symptoms soon after the administration of a long-acting gonadotropin-releasing hormone agonist for treatment of a prostate cancer. Imaging revealed a destructively growing and extensively calcified sellar mass inconsistent with a pituitary adenoma. A transseptal transsphenoidal tumor mass reduction yielded a histological diagnosis of a collision tumor comprised of a gonadotroph adenoma intermingled with osteochondroma. We discuss a potential causal relationship between the administration of the long-acting gonadotropin-releasing hormone agonist and the sudden appearance of the previously unsuspected sellar lesion. Although the association of these two tumors is very likely coincidental, the possibility of causal relationship is addressed.

D-Dimers Predict Stroke Subtype when Assessed Early

Early classification of ischemic stroke subtype is important for secondary stroke prevention and may guide further investigations.

Landscape and well-being: a scoping study on the health-promoting impact of outdoor environments

OBJECTIVES: The present literature review conceptualises landscape as a health resource that promotes physical, mental, and social well-being. Different health-promoting landscape characteristics are discussed. METHODS: This article is based on a scoping study which represents a special kind of qualitative literature review. Over 120 studies have been reviewed in a five-step-procedure, resulting in a heuristic device. RESULTS: A set of meaningful pathways that link landscape and health have been identified. Landscapes have the potential to promote mental well-being through attention restoration, stress reduction, and the evocation of positive emotions; physical well-being through the promotion of physical activity in daily life as well as leisure time and through walkable environments; and social well-being through social integration, social engagement and participation, and through social support and security. CONCLUSION: This scoping study allows us to systematically describe the potential of landscape as a resource for physical, mental and social well-being. A heuristic framework is presented that can be applied in future studies, facilitating systematic and focused research approaches and informing practical public health interventions.

Working Alliance Inventory-Short Revised (WAI-SR): psychometric properties in outpatients and inpatients

The Working Alliance Inventory-Short Revised (WAI-SR) is a recently refined measure of the therapeutic alliance that assesses three key aspects of the therapeutic alliance: (a) agreement on the tasks of therapy, (b) agreement on the goals of therapy and (c) development of an affective bond. The WAI-SR demonstrated good psychometric properties in an initial validation in psychotherapy outpatients in the USA. The generalizability of these findings is limited because in some countries a substantial portion of individual psychotherapy is delivered in inpatient settings. This study investigated and compared the psychometric properties of the WAI-SR in German outpatients (N = 88) and inpatients (N = 243). In both samples reliability (alpha > 0.80) and convergent validity with the Helping Alliance Questionnaire were good (r > 0.64). Confirmatory factor analysis showed acceptable to good model fit for the proposed Bond-Task-Goal model in both samples. Multi-group analysis demonstrated that the same constructs were measured across settings. Alliance ratings of outpatients and inpatients differed regarding the overlap of alliance components and the magnitude of the alliance ratings: The differentiation of the alliance components was poorer in inpatients and they reported lower alliances. Unique aspects of the alliance in inpatient treatment are discussed and a need for further research on the alliance in inpatient settings is pointed out. Overall, the WAI-SR can be recommended for alliance assessment in both settings.