The antioxidant 2,6-di-tert-butylphenol moiety attenuates the pro-oxidant properties of the auranofin analogue.

Metal-based drugs are gaining momentum as a rapidly developing area of medicinal inorganic chemistry. Among gold pharmaceuticals, auranofin is a well known antirheumatic drug. The efficacy of gold-organic complexes largely depends on their pro-oxidant properties since auranofin targets the redox enzyme thioredoxin reductase (TrxR). However, an uncontrollable oxygen burst may be harmful for healthy cells; therefore, the search for chemical modifications to attenuate oxidation-related general toxicity of gold containing anti-inflammatory drugs is justified. In this study, we demonstrate that the incorporation of a specific antioxidant phenol fragment can counterbalance the pro-oxidative potential of the Au containing complex molecule. The electrochemical studies of AuPPh3SR (1, R= 3,5-di-tert-butyl-4-hydroxyphenyl) and its precursors AuPPh3Cl (2) and RSH (3) showed that complex 1 and phenol 3 efficiently scavenged the radicals (as detected by cyclic voltammetry) whereas 2 had no effect. Compound 1 inhibited TrxR in vitro with IC50 0.57 ± 0.15 µM, a value one order of magnitude bigger than the potency reported for auranofin. Compound 1 (5 mg kg-1 daily gavage for 14 days) caused a decrease in ex vivo spontaneous and ascorbate-induced lipid peroxidation in the homogenates of rat lung, heart muscle, spleen, liver, kidneys, testicles and brain as assessed by the thiobarbituric acid reactive substances. Importantly, in animals fed with 1, no discernible general toxicity was registered suggesting that this compound is well tolerated. Our results provide evidence for an efficient synthetic route to obtain gold containing anti-inflammatory drug candidates with balanced pro/anti-oxidative properties.

Low FoxG1 and high Olig-2 labelling indices define a prognostically favourable subset in isocitrate dehydrogenase (IDH)-mutant gliomas.

AIMS: Previous data suggest that expression of transcription factors FoxG1 and Olig-2 can separate hotspot histone H3 family member 3A (H3F3A)-mutant tumours in paediatric glioma. We evaluated their prognostic potential and feasibility for identifying H3F3A-mutant tumours among IDH-mutant/wild-type gliomas. METHODS: Immunohistochemistry of FoxG1/Olig-2 and α-thalassaemia/mental-retardation-syndrome-X-linked gene (ATRX) in 471 cases of diffuse gliomas and molecular determination of IDH, H3F3A, MGMT and 1p/19 codeletion status. RESULTS: Mean percentage of FoxG1-positive tumour cells increased from 17% in WHO grade II to over 21% in grade III to 37% in grade IV tumours, whereas mean Olig-2 indices decreased from 29% to 28% to 17% respectively. FoxG1 indices were similar in astrocytic and oligodendroglial tumours, whereas Olig-2 indices were increased in oligodendrogliomas compared to astrocytic tumours (n = 451, P < 0.0001). FoxG1-positive nuclei were significantly reduced in IDH and H3F3A K27-mutant tumours, whereas Olig-2-positive nuclei were significantly reduced in IDH-wild-type and H3F3A G34-mutant tumours. Among IDH-mutant tumours, mean Olig-2 index was significantly higher in 1p/19q codeleted tumours (mean: 43%) compared to IDH-mutant tumours with ATRX loss (mean: 23%, P < 0.0001). A significantly better outcome was first suggested for FoxG1low tumours (n = 212, log rank P = 0.0132) and Olig-2high tumours (n = 203, log-rank P = 0.0011) based on classification and regression tree determined cutoffs, but this was not confirmed by multivariate analysis including IDH mutation, WHO grade, ATRX status and age. CONCLUSIONS: While the combined FoxG1/Olig-2 profile may discriminate H3F3A K27- and G34-mutant tumours and define a prognostically favourable subset in IDH-mutant gliomas, our data show that labelling indices of these transcription factors overlap with adult IDH-mutant and wild-type tumour classes.

The anticoagulant effect of heparin during radiofrequency ablation (RFA) in patients taking apixaban or rivaroxaban.

PURPOSE: Measuring the anticoagulant effect of heparin during radiofrequency ablation (RFA) in patients taking apixaban and rivaroxaban is challenging, since the activated coagulation time (ACT) does not seem to reflect the true anticoagulant activity of these drugs. We therefore evaluated coagulation properties of apixaban and rivaroxaban during RFA by different coagulation assays to better monitor periprocedural hemostasis. METHODS: The study included 90 patients (61 ± 12 years) with atrial fibrillation who underwent RFA procedures. Patients received 20 mg rivaroxaban (n = 73) once or 5 mg apixaban (n = 17) twice daily 4 weeks prior to the procedure. During RFA, unfractionated heparin i.v. was given to maintain an ACT of 250-300 s. Blood samples were taken before and 10, 60, and 360 min after heparin administration. RESULTS: Heparin displayed a lower anti-Xa activity in rivaroxaban-treated patients compared to apixaban-treated patients. In contrast, D-dimer and prothrombin fragment F1+2 plasma levels indicated a higher activation of the coagulation cascade in apixaban/heparin than in rivaroxaban/heparin patients. This discordant coagulative state measured in vitro had no clinical impact in terms of bleeding or thromboembolic complications. CONCLUSION: We found different biochemical responses to rivaroxaban/heparin and apixaban/heparin during RFA. Precaution is necessary when monitoring periprocedural hemostasis in DOAC patients to avoid mismanagement.

Effect of the FXa inhibitors Rivaroxaban and Apixaban on platelet activation in patients with atrial fibrillation.

Rivaroxaban and Apixaban, increasingly used for stroke prevention in non-valvular atrial fibrillation (AF), might impact platelet reactivity directly or indirectly. By inhibition of Factor Xa (FXa) they preclude not only generation of relevant thrombin amounts but also block signalling of FXa via protease activated receptors. However, weather FXa-inhibition affects platelet haemostasis remains incompletely known. One hundred and twenty-eight patients with AF on chronic anticoagulation with either Rivaroxaban or Apixaban for at least 4 weeks were included in the study. In a time course group (25 on Rivaroxaban, 13 on Apixaban) venous blood samples were taken before NOAC medication intake in the morning as well as 2 and 6 h afterwards. In 90 patients (Rivaroxaban n = 73, Apixaban n = 17) blood samples were drawn during left atrial RFA procedures before as well as 10 and 60 min after the first heparin application (RFA group). Platelet reactivity analyzed by whole blood aggregometry (Multiplate Analyzer, Roche) in response to ADP, Collagen, TRAP and ASPI (arachidonic acid) was not altered by Rivaroxaban or Apixaban neither in the time course nor in the RFA group. Moreover, soluble P-selectin, Thrombospondin, von Willebrand Factor and beta thromboglobulin plasma levels, measured by ELISA, showed no statistically significant changes in both clinical settings for either FXa-inhibitor. The present study fails to demonstrate any significant changes on platelet reactivity in patients with AF under chronic Rivaroxaban or Apixaban medication, neither for trough or peak levels nor in case of a haemostatic activation in vivo as depicted by RFA procedures.

Improved self- and external assessment of the clinical abilities of medical students through structured improvement measures in an internal medicine bedside course.

BACKGROUND: Bedside courses are of outstanding importance when training medical students. The fact that less and less teaching is taking place nowadays at the patient's bedside makes it all the more important that the available time be put to effective use. The aim of this study was to check whether structured improvement measures in the course (scripts, lecturer briefing, e-learning cases) would improve the abilities of the students on the basis of a subjective self-assessment as well as an external assessment by the lecturers with respect to clinical abilities. METHODS: Bedside teaching takes place in the fourth study year in the Medical Clinics of the TU Munich. Both students and lecturers had the chance to hand in an anonymous, quantitative self- and external assessment of the clinical abilities of the students (German grading system) after every course date. This assessment took place online in the three categories "Medical history & examination", "Diagnosis" and "Therapy". An overall period of four semesters, each with 6 course dates, was investigated. After two of the total of four semesters in the study, the course was changed by introducing scripts, lecturer briefing as well as interactive e-learning cases. The self- and external assessment was compared both within the semester (date 1-3: A; date 4-6: B), during the course as well as before and after introducing the improvement measures ("before" (T0): SS 2012, SS 2013, "after" (T1): WS 2013/2014, SS 2014). RESULTS: There was a significant improvement in one's own abilities on the basis of the self-assessment within each semester when comparing the first (A) and the last (B) course dates. Moreover, there was a significant improvement in the performances in all three categories when T0 was compared with T1, from both the point of view of the students ("Medical history & examination": T0 =2.5±0.9, T1=2.2±0.7, pp<0.001; "Diagnosis" T0=3.1±1.0, T1=2.8 ±0.9, pp<0.001; "Therapy": T0=3.8±1.3, T1=3.5±1.2, pp<0.018) and in two of the three categories from the point of view of the lecturers ("Diagnosis": T0=3.0±1.0, T1=2.7±0.7, p.=0.028; "Therapy": T0=3.8±1.1, T1=3.1±1.0, p<0.001). SUMMARY: The structured measures to improve the course including the interactive e-learning cases could have contributed to improved practical abilities with respect to the medical history and examination techniques as well as diagnostic and therapeutic thinking. The external evaluation by lecturers confirmed the improvement with respect to the diagnostic and therapeutic abilities. They only saw no dynamic change in the student's taking histories and clinical examinations.

Cobaltoceniumethynyl gold(I) as an unusual heterodinuclear bioorganometallic fragment to study the biological properties of alkynyl gold complexes.

A cobaltoceniumethynyl gold(i) complex with a triphenylphosphane ligand triggered efficient cytotoxic effects in cancer cells in contrast to a derivative with two cobaltocenium moieties. The complex effectively inhibited the enzyme thioredoxin reductase (TrxR) suggesting this enzyme as a possible biological target. The cellular uptake of both metal fragments of the active complex was studied by atomic absorption spectroscopy and indicated a high biological stability of the complex.

[New ESH/ESC guidelines on arterial hypertension : what is new and what indications remain for renal denervation?]. / Neue ESH/ESC-Leitlinien für die arterielle Hypertonie : Was ist neu, und welche Indikation bleibt für die renale Denervierung?

Arterial hypertension is one of the most common diseases in the western world and one of the most important risk factors for other cardiovascular diseases. Despite widespread therapeutic options, there is still a large proportion of patients with uncontrolled hypertension. The new European guidelines on hypertension give clear lines of action for diagnosis and treatment sorted into appropriate evidence levels based on current scientific data. Such evidence is still unclear for renal denervation so that no clear recommendations can be given.

Safety and efficacy of the Yukon Choice Flex sirolimus-eluting coronary stent in an all-comers population cohort.

AIMS: The use of biodegradable-polymer drug-eluting stents has been shown to provide favorable results when compared with durable polymer drug-eluting stents and long-term follow up data have recently shown significant reductions in terms of very late stent thrombosis. Aim of the present study was to assess the safety and efficacy profile of a novel biodegradable polymer DES, the Yukon Choice Flex sirolimus-eluting stent. METHODS: We report here the one-year clinical outcomes associated with the use of the Yukon Choice Flex sirolimus-eluting stent in an all-comers patient population. The present stent represents a further refinement of the stent platform tested in the ISAR TEST 3 and 4 randomized clinical trials. A total of 778 consecutive patients undergoing implantation of this stent were enrolled in the present observational study and prospectively followed for one year. RESULTS: The use of the Yukon Choice Flex stent in a patient population with complex coronary lesion morphology was associated with optimal immediate angiographic results. At one year follow up the rates of death, myocardial infarction, definite stent thrombosis and ischemia-driven target lesion revascularization were respectively 2.4%, 1.9%, 0.3% and 11.3%. CONCLUSIONS: The use of the sirolimus-eluting biodegradable polymer Yukon Choice Flex stent in an all-comers population of patients with complex coronary artery disease is associated with a favorable safety and efficacy profile up to one year follow up.

Antiglioma activity of GoPI-sugar, a novel gold(I)-phosphole inhibitor: chemical synthesis, mechanistic studies, and effectiveness in vivo.

Glioblastoma, an aggressive brain tumor, has a poor prognosis and a high risk of recurrence. An improved chemotherapeutic approach is required to complement radiation therapy. Gold(I) complexes bearing phosphole ligands are promising agents in the treatment of cancer and disturb the redox balance and proliferation of cancer cells by inhibiting disulfide reductases. Here, we report on the antitumor properties of the gold(I) complex 1-phenyl-bis(2-pyridyl)phosphole gold chloride thio-ß-d-glucose tetraacetate (GoPI-sugar), which exhibits antiproliferative effects on human (NCH82, NCH89) and rat (C6) glioma cell lines. Compared to carmustine (BCNU), an established nitrosourea compound for the treatment of glioblastomas that inhibits the proliferation of these glioma cell lines with an IC50 of 430µM, GoPI-sugar is more effective by two orders of magnitude. Moreover, GoPI-sugar inhibits malignant glioma growth in vivo in a C6 glioma rat model and significantly reduces tumor volume while being well tolerated. Both the gold(I) chloro- and thiosugar-substituted phospholes interact with DNA albeit more weakly for the latter. Furthermore, GoPI-sugar irreversibly and potently inhibits thioredoxin reductase (IC50 4.3nM) and human glutathione reductase (IC50 88.5nM). However, treatment with GoPI-sugar did not significantly alter redox parameters in the brain tissue of treated animals. This might be due to compensatory upregulation of redox-related enzymes but might also indicate that the antiproliferative effects of GoPI-sugar in vivo are rather based on DNA interaction and inhibition of topoisomerase I than on the disturbance of redox equilibrium. Since GoPI-sugar is highly effective against glioblastomas and well tolerated, it represents a most promising lead for drug development. This article is part of a Special Issue entitled: Thiol-Based Redox Processes.

Significant improvement of a clinical training course in physical examination after basic structural changes in the teaching content and methods.

BACKGROUND: Regular student evaluations at the Technical University Munich indicate the necessity for improvement of the clinical examination course. The aim of this study was to examine if targeted measures to restructure and improve a clinical examination course session lead to a higher level of student satisfaction as well as better self-assessment of the acquired techniques of clinical examination. METHODS: At three medical departments of the Technical University Munich during the 2010 summer semester, the quantitative results of 49 student evaluations (ratings 1-6, German scholastic grading system) of the clinical examination course were compared for a course before and a course after structured measures for improvement. These measures included structured teaching instructions, handouts and additional material from the Internet. RESULTS: 47 evaluations were completed before and 34 evaluations after the measures for improvement. The measures named above led to a significant improvement of the evaluative ratings in the following areas: short introduction to the topic of each clinical examination course (from 2.4±1.2 to1.7±1.0; p=0.0020) and to basic measures of hygiene (from 3.8±1.9 to 2.5±1.8; p=0.004), structured demonstration of each clinical examination step (from 2.9±1.5 to 1.8±1.0; p=0.001), sufficient practice of each clinical examination step (from 3.1±1.8 to 2.2±1.4; p=0.030) structured feedback on each clinical examination step (from 3.0±1.4 to 2.3±1.0; p=0.0070), use of handouts (from 5.2±1.4 to 1.8±1.4; p<0.001), advice on additional learning material (from 5.0±1.4 to 3.4±2.0; p<0.001), general learning experience (from 2.4±0.9 to 1.9±0.8; p=0.017), and self-assessment of the acquired techniques of clinical examination (from 3.5±1.3 to 2.5±1.1; p<0.01). CONCLUSION: Structured changes led to significant improvement in the evaluative ratings of a clinical examination course session concerning preparation of the tutors, structure of the course, and confidence in performing physical examinations.

Radioterapia hipofraccionada en el tratamiento preservador del cáncer de mama en estadio precoz resultados preliminares / Hypo fraction radiation therapy in the preserved tratment of early breast cancer

Resultados preliminares del tratamiento con radioterapia hipofraccionada, en pacientes con cáncer de mama en estadio precoz, y cirugía preservadora. Análisis retrospectivo de 64 pacientes estadios 0, I y II, ganglios negativos, tratadas entre marzo 2009 abril 2011. Tratamiento con planificación conformada tridimensional, dosis de 42,6 Gy en 16 fracciones de 2,66 Gy a toda la mama, más dosis adicional de 7,98 Gy en 3 fracciones al lecho del tumor primario. La distribución por estadios fue: estadio 0 15/ 64 pacientes 23,4%; estadio I 41/64 64,1%, estadio II 8/64 12,6%. Seguimiento de 1 a 2,3 meses, promedio 4,4 meses. Todas las pacientes se encuentran vivas, libres de enfermedad hasta el momento. Complicaciones agudas: 85,94 radiodermatitis grado 0-I (55/64), 7,81% radiodermatitis grado II (5/64),3,1% grado III (2/64) y 2 pacientes no fueron evaluables, 6-24 meses después de finalizar la irradiación, 53,1% no presentó complicaciones, 32,8% (21/64) presentaron radiodermatitis grado I (eritema, hiperpigmentación), 1,6% (1) dermatitis grado II, 2 pacientes dermatitis grado III,6/64 (9,3%). 3 estudios aleatorios han demostrado la efectividad de los regímenes de hipofraccionamiento, resultados comparables a los esquemas de fraccionamiento convencional. Los resultados preliminares, nos animan a continuar el empleo de estos esquemas de radioterapia en la práctica clínica. Es necesario un mayor tiempo de seguimiento en la serie de pacientes presentadas, para evaluar los resultados de control local, sobrevida y morbilidad tardía por radioterapia

Preliminary results obtained with hypo fractionated radiotherapy in patients with early breast cancer who have undergone breast conserving surgery. Retrospective analysis 64 patients treated from March 2009- April 2011. Treated with 3D conformal radiation therapy; dose 42.6 Gy in 16 fractions 2.66 Gy was given to the breast followed by a boost to tumor bed of 7.98 Gy in 3 fractions. Distribution according to stage was: Stage 0 15/64 patients 23.4%; stage I 41/64 64.1% and stage II 8/64 12.6%. Mean follow up 4, 4 months, with range 1 to 2.3 months. All patients are alive and free of disease, at moment analysis the data. Acute complications: Grade 0-1 skin reactions 85.94% (55/64 ), grade II 7.81% (5/64 ), grade III 3,1% (2/64), 2 patients could not be evaluated. 6-24 months after completion treatment 53,1% had no complications; 32.8% (21/64) grade I dermatitis (Erythema, hyper pigmentation); 1.6% (1) grade II, 2 patients grade III dermatitis, 6/64 patients (9.3%) there was mild subcutaneous fibrosis. 3 randomized clinical trials, regimens of hypo fraction y have produced results comparable to conventional fractionation. The preliminary results of this study are encouraging; we continue to apply this regimen in the clinical practice. Obviously a longer follow up time is necessary to determine results regarding survival, local control and chronic complications of radiotherapy in the present study

Erythropoietin-induced progenitor cell mobilisation in patients with acute ST-segment-elevation myocardial infarction and restenosis.

Erythropoietin improves myocardial function and enhances re-endothelialisation. Aim of this study was to analyse progenitor cell mobilisation and restenosis in patients from the Regeneration of Vital Myocardium in ST-Segment Elevation Myocardial Infarction by Erythropoietin (REVIVAL-3) study. Patients with STEMI undergoing percutaneous coronary intervention (PCI) were randomly assigned to Epoetin beta (EPO) (n=68) or placebo (n=70). Drug-eluting stents (DES) were utilised in 93% of patients receiving EPO and in 95% of patients receiving placebo (p=0.83). Serial venous blood samples were drawn; CD133+ progenitor cells were quantified by four-colour flow cytometry and cytokines interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL-12 and tumour necrosis factor (TNF) alpha were analysed by cytometric bead array. Forty-eight hours after PCI a significant increase in CD133+ progenitor cells was observed in the EPO group. Yet, no differences in plasma cytokines were found. Quantitative coronary angiography after six months revealed an increase in segment diameter stenosis in the EPO group (32 ± 19% vs. 26 ± 14%, p=0.046). However, this increase in neointima generation was not associated with progenitor cell mobilisation. EPO in patients with STEMI treated with PCI is associated with an increase in diameter stenosis that is not associated with circulating progenitor cells.

Radioterapia estereotáctica extracraneal un nuevo paradigma: en terapéutica oncológica: experiencia preliminar / Extra cranial stereotactic radiation therapy: a new paradigm in oncology therapeutic: preliminar experience

Presentar resultados preliminares del tratamiento con radioterapia estereotáctica extracraneal en metástasis hepáticas, tumores pulmonares y otras lesiones metastásicas. Se describe método terapéutico y se presenta un análisis prospectivo de 25 pacientes tratados en el servicio de radioterapia la Trinidad con esta modalidad de radioterapia de alta precisión, desde marzo de 2009. Se utilizó un acelerador lineal Varian® IX versión Trilogy con equipo de imágenes incorporado. Las dosis de radioterapia oscilaron entre 60 Gy en 3 fracciones a 44,5 Gy en 10 fracciones. El tiempo de seguimiento osciló de <1 mes a 16 meses. Se incluyeron un total de 25 individuos (44 lesiones); 14 pacientes con metástasis hepáticas, 5 con metástasis pulmonares (3 de ellos también recibieron tratamiento por metástasis hepáticas), 4 con tumores primarios de pulmón, 2 con metástasis vertebrales y 3 con otras lesiones secundarias. La tolerancia al tratamiento fue en general satisfactoria, sin complicaciones severas. Se observó estabilización o regresión parcial de las lesiones en 17 pacientes, persistencia o progresión local en 3 pacientes. En 13 individuos la enfermedad a distancia permaneció estable y en 10 ocurrió progresión de la misma, durante este tiempo limitado de seguimiento. Cuatro pacientes han fallecido con enfermedad. La radioterapia extracraneal estereotáctica es una modalidad terapéutica novedosa, con gran potencial en el manejo multidisciplinario de las enfermedades neoplásicas. Los resultados preliminares de este trabajo, demuestran su efectividad, seguridad y la factibilidad de su aplicación en nuestro país

Present the preliminary results obtained with stereotactic body radiation therapy in liver metastases, pulmonary tumors and other metastatic lesions. Treatment is described, presenting a prospective analysis of 25 patients treated in La Trinidad Radiation Therapy Service since March 2009. Patients were treated using a dual energy IX Varian® linear accelerator Trilogy version, with on board imaging. Doses of radiation varied from 60 Gy in 3 fractions to 44.5 Gy in 10 fractions. Follow up time varied from < 1 month to 16 months. Total of 25 patients were included in the study (44 lesions); 14 patients with liver metastases, 5 with lung metastases (3 of them also received treatment for liver metastases), 4 primary lung tumors, 2 vertebral metastases, and 3 with other metastatic lesions. Treatment was in general well tolerated with no serious complications. Partial regression or stabilization of the treated lesions occurred in 17 patients, persistence or local progression was seen in 3 patients. In 13 individuals there was no appearance of new metastatic disease and 10 showed progression of distant disease, during this limited follow up time. Four patients have died with disease. Stereotactic body radiation is a novel high precision radiation therapy technique with a great potential in the multidisciplinary management of patients with neoplastic disease. The preliminary results of this study and the review of the literature support the safety, and effectiveness of this treatment modality and the feasibility of employing in Venezuela

Circulating tissue factor and microparticles are not increased in patients with deep vein thrombosis.

BACKGROUND: Circulating tissue factor (TF) is associated with inflammation and may contribute to thrombotic events. Aim of this study was to analyze circulating TF activity and proinflammatory cytokines in patients with deep venous thrombosis. PATIENTS AND METHODS: Forty-eight patients with deep vein thrombosis and 45 control subjects were included. Venous blood samples were obtained at diagnosis for analysis of TF activity, TF antigen, prothrombin fragment F1 + 2, microparticles (expressing phosphatidylserine and supporting FXa generation), Interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-12 and tumor-necrosis-factor-alpha (TNF). RESULTS: TF antigen, activity and microparticles were similar in both groups: In contrast, a significant increase in plasma IL-6, IL-8 and F1 + 2 levels was found in thrombosis. This increase in IL-6 and IL-8 as well as F1 + 2 was not correlated with the extent of thrombosis, predisposing factors or onset of symptoms. CONCLUSIONS: Circulating TF and microparticles are not elevated in deep venous thrombosis. The increase in IL-6, IL-8 and F1 + 2 during thrombosis was not proportional to the extent or predisposing risk factors.

[Traumatic optic neuropathy: a review of the literature in the light of personal experiences]. / Die traumatische Optikusneuropathie: Aktuelle Literaturübersicht im Spiegel eigener Erfahrungen.

BACKGROUND: Therapy of traumatic optic neuropathy (TON) is still discussed controversially. Studies of medical treatment and surgical decompression of the nerve could not find any correlation between therapy and result. Today's knowledge of the treatment in TON is to be analyzed by the latest results in the literature, supplemented by personal experiences with our own patients, who underwent a combination of corticosteroids and surgical decompression. METHODS: The study group consisted of 9 patients at the age of 13-58 years. 8 patients suffered from a cranial trauma, 1 patient had sinus surgery, which resulted in an indirect damage of the optic nerve. Pretherapeutically, 5 patients had residual vision, 4 patients were blind. A fracture line through the optic canal in the CT-scan was seen in 6 cases. Decompression was performed within 24 hours in 3 cases; in the worst 3 cases it took up to 8 days. In 8 patients the intervention was performed via an endonasal, microscopic-endoscopic approach, once it was done transfacially. Simultaneously, high-dose corticosteroids were administered. RESULTS: All patients with a residual vision before therapy showed an improvement of their visual acuity: In the best case visual acuity changed from perception of light to 0.8. All patients with posttraumatic blindness remained blind after therapy. CONCLUSION: A surgical decompression may be considered in patients with residual vision. Referring to the latest data in the literature endonasal, microscopic-endoscopic decompression is then to be combined with simultaneous application of high-dose corticosteroids. In our opinion, a mere wait-and-see strategy completely without any treatment can hardly be recommended.

Tissue Factor-Factor VIIa complex induces cytokine expression in coronary artery smooth muscle cells.

OBJECTIVE: Within atherosclerotic lesions Tissue Factor (TF)-Factor VIIa (FVIIa) not only contributes to thrombotic events but also alters vascular remodeling through enhancement of migration. Moreover, the TF-FVIIa-FXa complex activates protease-activated receptors (PAR). TF/FVIIa/PAR-2 signaling has also been shown to promote proliferation and metastasis of tumor cells. Since coagulation factors promote inflammation which plays a major role during atherosclerosis as well as tumor metastasis this study sought to investigate the effects of FVIIa on the inflammatory response in vascular cells. METHODS/RESULTS: FVIIa induces interleukin-8 (IL-8) and IL-6 in primary smooth muscle cells (SMC), which was correlated to the expression of TF and PAR-2 as shown by immunoassay and qRT-PCR. The effect was dose-dependent and required TF, the proteolytic activity of FVIIa and PAR-2. Secondary effects of downstream coagulation factors were excluded. No proinflammatory FVIIa effect was observed in endothelial cells (EC) and mononuclear cells (MNC), expressing either TF or PAR-2. In atherosclerotic lesions mRNA expression of PAR-1, PAR-2 and IL-8 was elevated compared to healthy vessels indicating a role for PAR-1 and PAR-2 signaling in atherosclerosis. CONCLUSION: In addition to the procoagulant and promigratory role of the TF-FVIIa complex we identify a proinflammatory role of FVIIa in human SMC dependent on expression of TF and PAR-2 that provides yet another link between coagulation and inflammation.

[Multifocal manifestation of Rosai-Dorfman disease. A rare case of purely extranodal sinus histiocytosis in the elderly]. / Multifokale Manifestation einer Rosai-Dorfman-Erkrankung. Seltene, rein extranodale Sinushistiozytose im Erwachsenenalter.

Rosai-Dorfman disease belongs to the group of childhood histiocytoses and was initially described as sinus histiocytosis with massive lymphadenopathy. Its rare purely extranodal manifestation is primarily found in the head and neck region. An atypical primary manifestation in an elderly patient with multifocal extranodal disease is described, and this pathological entity is reviewed. Specific difficulties concerning differential diagnostic aspects as well as individually appropriate treatment strategies are discussed.

[Atypical gout tophi for differential diagnosis of head and neck tumors : case report and review of the literature]. / Atypische Gichttophi als Differenzialdiagnose von HNO-Tumoren : Fallbericht und Literaturübersicht.

Gout is a mostly hereditary metabolic disease and is considered a disease of affluence. The disease is promoted by a purine-rich diet and shows an intermittent course of inflammatory joint manifestations and periods free of symptoms. The pathognomonic sign of the disease is an acute and very painful monarthritis with typical local deposits of uric acid, so-called gout tophi. No or inadequate treatment leads to the chronic form of gouty arthritis characterized more by joint destruction than by persistent pain. In head and neck gout tophi are seen as nodular lesions along the outer helical edges of the auricle. A case report of gout manifestation in the infratemporal fossa, deriving from the temporomandibular joint, with arrosion of the bony skull base demonstrates gout as a relevant disease for the ENT clinician. Potential diagnostic difficulties as well as recommendations for a therapeutic regimen of gouty lesions in such critical localizations will be reviewed.