[102 patients with suspected myocarditis : Clinical presentation, diagnostics, therapy and prognosis]. / 102 Patienten mit Verdacht auf Myokarditis : Klinische Präsentation, Diagnostik, Therapie und Prognose.

INTRODUCTION: Myocarditis is a disease which is difficult to diagnose and which includes a risk of the development of dilated cardiomyopathy and sudden cardiac death. METHODS AND PATIENTS: In this study 102 patients were included from the time period 2003-2013 after diagnosis or suspected diagnosis of myocarditis in the department of internal medicine at the University Hospital Halle (Saale). RESULTS: Of the study participants 77.5% were male and the average age was 35.5 ± 14.1 years. The symptoms reported by the patients were angina in 46.1%, dyspnea in 38.2%, performance deterioration in 29.4%, palpitations in 9.8% and syncope in 8.8%. In 45.1% of patients, symptoms were preceded by a respiratory infection. All patients underwent an echocardiogram and in 36.5% it was possible to demonstrate a regional wall motion abnormality and in 20.4% a pericardial effusion. A myocardial biopsy was performed in 15.6% of the patients. The presence of cardiotropic viruses was investigated in 37.3% of patients but was detected in only 5.9%. Cardiac magnetic resonance imaging (MRI) was performed in 82 patients of whom 33.3% showed a late enhancement and 11.9% a wall movement disorder. In this study four patients, all male, died and three suffered recurrent myocarditis. CONCLUSION: This study showed the wide range of symptoms in myocarditis. Myocarditis is rarely severely manifested and in this study the mortality was 3.9%. For further optimization of the diagnostic and treatment algorithms, prospective, randomized studies would be desirable.

Fibroblast growth factor 2 is of prognostic value for patients with locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND AND PURPOSE: Patients with locally advanced SCCHN have a poor prognosis. This study investigated the prognostic value of the tumor cell expression of the fibroblast growth factor 2 (FGF-2) in patients treated with surgery followed by radiotherapy. PATIENTS AND METHODS: The impact of FGF-2-expression and 11 additional potential prognostic factors on loco-regional control (LRC), metastases-free survival (MFS), and overall survival (OS) was retrospectively evaluated in 146 patients. Additional factors included age, gender, performance status, pre-radiotherapy hemoglobin levels, tumor site, histologic grade, T-category, N-category, human papilloma virus (HPV) status, extent of resection, and chemotherapy. Univariate analyses were performed with the Kaplan-Meier method and the log-rank test, multivariate analyses with the Cox proportional hazard model. RESULTS: On multivariate analysis, improved LRC was significantly associated with FGF-2-negativity [risk ratio (RR): 7.33; 95%-confidence interval (CI): 2.88-19.05; p<0.001], lower T-category (RR: 2.42; 95%-CI: 1.47-4.33; p<0.001), lower N-category (RR: 12.36; 95%-CI: 3.48-78.91; p<0.001), and pre-radiotherapy hemoglobin levels ≥ 12 g/dl (RR: 4.18; 95%-CI: 1.73-10.53; p=0.002). No factor was significantly associated with improved MFS. Lower T-category showed a trend (RR: 1.59; 95%-CI: 0.97-2.82; p=0.069). Better OS was significantly associated with FGF-2-negativity (RR: 5.10; 2.22-11.80; p<0.001), lower T-category (RR: 2.17; 95%-CI: 1.38-3.68; p < 0.001), lower N-category (RR: 3.86; 95%-CI: 1.60-10.85; p=0.002), and pre-radiotherapy hemoglobin levels ≥ 12 g/dl (RR: 3.20; 95%-CI: 1.46-7.30; p=0.004). HPV-positivity showed a trend (RR: 2.36; 95%-CI: n.a.; p=0.054). CONCLUSIONS: Tumor cell expression of FGF-2 proved to be an independent prognostic factor for LRC and OS. This factor can help personalize treatment and stratify patients in future trials.

Androgen receptor expression: prognostic value in locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND AND PURPOSE: This study investigated the prognostic value of androgen receptor (AR) expression of tumor cells in patients treated with surgery and subsequent radio(chemo)therapy for locally advanced squamous cell carcinoma of the head and neck (SCCHN). MATERIAL AND METHODS: The impact of AR and 11 additional factors on locoregional control (LRC), metastases-free survival (MFS), and overall survival (OS) was retrospectively studied in 163 patients with nonmetastatic stage III/IV SCCHN. Additional factors included age, gender, ECOG performance status, pre-radiotherapy (pre-RT) hemoglobin levels, tumor site, histologic grade, T category, N category, HPV status, extent of resection, and concurrent chemotherapy. RESULTS: On multivariate analysis, improved LRC was significantly associated with pre-RT hemoglobin levels≥12 g/dl (risk ratio [RR] 2.22; 95% confidence interval [CI] 1.19­4.13; p=0.013), tumor site (RR 1.39; 95% CI 1.14­1.70; p=0.001), lower T category (RR 1.67; 95% CI 1.18­2.44; p=0.003), and lower N category (RR 4.18; 95% CI 1.90­10.55; p<0.001). Improved MFS was associated with AR expression (RR 2.21; 95% CI 1.01­5.41; p=0.048), better ECOG performance status (RR 3.19; 95% CI 1.50­7.14; p=0.003), lower T category (RR 2.24; 95% CI 1.47­3.65; p<0.001), and lower N category (RR 5.33; 95% CI 2.07­16.63; p<0.001). OS was positively associated with AR expression (RR 1.99; 95% CI 1.06­4.00; p=0.032), better ECOG performance status (RR 2.20; 95% CI 1.20­4.09; p=0.010), pre-RT hemoglobin levels≥12 g/dl (RR 2.13; 95% CI 1.19­3.82; p=0.012), lower T category (RR 1.81; 95% CI 1.30­2.62; p<0.001), and lower N category (RR 3.41; 95% CI: 1.65­7.80; p<0.001). CONCLUSION: Tumor cell expression of AR was an independent prognostic factor for MFS and OS and should be considered in future prospective trials.

Prognostic impact of VEGF and FLT-1 receptor expression in patients with locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND AND PURPOSE: This study investigated the prognostic value of tumor cell expression of vascular endothelial growth factor (VEGF) and its receptor fms-related tyrosine kinase 1 (FLT-1) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) who had been treated with adjuvant radiotherapy or radiochemotherapy. MATERIAL AND METHODS: The impact of tumor cell VEGF and FLT-1 expression plus 11 additional factors on loco-regional control (LRC), metastases-free survival (MFS) and overall survival (OS) was retrospectively evaluated in 157 patients. The additional factors were age, gender, performance status, pre-radiotherapy (pre-RT) hemoglobin levels, tumor site, histologic grade, T-category, N-category, human papillomavirus (HPV) status, extent of resection and chemotherapy. RESULTS: On multivariate analysis, improved LRC was significantly associated with an absence of VEGF expression (risk ratio, RR: 5.02; p = 0.009), lower T-category (RR: 2.00; p < 0.001), lower N-category (RR: 3.75; p < 0.001) and pre-RT hemoglobin levels ≥ 12 g/dl (RR: 2.20; p = 0.029). Improved MFS was significantly associated with an absence of VEGF expression (RR: 7.46; p = 0.002), lower T-category (RR: 1.97; p = 0.002), lower N-category (RR: 3.29; p = 0.005) and a favorable tumor location (RR: 1.34; p = 0.033); HPV positivity showed a trend towards improved MFS (RR: 1.43; p = 0.09). Improved OS was significantly associated with an absence of VEFG expression (RR: 3.22; p = 0.041), pre-RT hemoglobin levels ≥ 12 g/dl (RR: 2.47; p = 0.009), lower T-category (RR: 1.92; p < 0.001) and lower N-category (RR: 3.39; p < 0.001). FLT-1 expression was significantly associated with LRC and OS in the univariate but not in the multivariate analysis. CONCLUSION: VEGF expression proved to be an independent negative predictor for LRC, MFS and OS in patients treated for locally advanced SCCHN with adjuvant radiotherapy or radiochemotherapy. FLT-1 expression was not significant in multivariate analyses.

Prognosis of patients with locally advanced squamous cell carcinoma of the head and neck. Impact of tumor cell expression of EPO and EPO-R.

BACKGROUND AND PURPOSE: This study investigated the prognostic role of tumor cell expression of erythropoietin (EPO) and its receptor (EPO-R) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) treated with surgery plus radiotherapy. PATIENTS AND METHODS: The impact of EPO, EPO-R, and 11 additional factors on locoregional control (LRC), metastases-free survival (MFS), and overall survival (OS) was retrospectively evaluated in 144 patients. Additional factors were age, gender, performance status, preradiotherapy (pre-RT) hemoglobin levels, tumor site, histologic grade, T category, N category, human papillomavirus (HPV) status, extent of resection, and chemotherapy. Univariate analyses were performed with the Kaplan-Meier method and the log-rank test, multivariate analyses with the Cox proportional hazard model. RESULTS: On multivariate analysis, improved LRC was significantly associated with no EPO expression (risk ratio [RR] 3.72; 95 % confidence interval [CI] 1.35-15.42; p = 0.008), lower T category (RR 1.60; 95 %CI 1.14-2.32; p = 0.005), and oropharynx or larynx cancer (RR 1.23; 95 %CI 1.02-1.49; p = 0.033). Improved MFS was significantly associated with no EPO expression (RR 5.45; 95 %CI 1.13-97.81; p = 0.031), lower T category (RR 1.66; 95 %CI 1.11-2.65; p = 0.013), lower N category (RR 2.44; 95 %CI 1.04-6.66; p = 0.039), HPV positivity (RR 3.14; 95 %CI not available; p = 0.034), and oropharynx or larynx cancer (RR 1.28; 95 %CI 1.01-1.61; p = 0.041). Improved OS was significantly associated with no EPO expression (RR 4.77; 95 %CI 1.63-20.68; p = 0.003), no EPO-R expression (RR 2.36; 95 %CI 1.22-4.92; p = 0.010), lower T category (RR 1.44; 95 %CI 1.04-2.04; p = 0.027), oropharynx or larynx cancer (RR 1.30; 95 %CI 1.08-1.57; p = 0.007), and pre-RT hemoglobin ≥ 12 g/dl (RR 1.94; 95 %CI 1.03-3.65; p = 0.042). CONCLUSION: EPO expression of tumor cells was an independent prognostic factor for LRC, MFS, and OS. EPO-R expression was an independent prognostic factor for OS.

Impact of the HPV-positivity definition on the prognostic value of HPV status in patients with locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND AND PURPOSE: This study re-evaluated the prognostic value of HPV status for loco-regional control (LRC), metastases-free survival (MFS), and survival (OS) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). A modified definition of HPV positivity was used in the current study compared to the authors' previous study. PATIENTS AND METHODS: In the previous study of the same 170 patients, a tumor was defined as HPV-positive if it showed a positive in situ hybridization result in ≥10% of tumor cells and/or positive p16 immunostaining. In the current analysis, tumors were considered HPV-positive only if they showed positive results for both in situ hybridization and p16 immunostaining. In addition to HPV status, the same 11 potential prognostic factors were investigated for treatment outcomes as in the preceding study. RESULTS: In the multivariate analysis of the current study, HPV positivity was significantly associated with improved LRC [risk ratio (RR) 9.78; p<0.001], MFS (RR 7.17; p=0.008), and OS (RR 6.61; p<0.001). In the previous study, HPV positivity was associated with LRC (RR 2.34; p=0.014) and OS (RR 2.19; p=0.019), but not with MFS (RR 2.04; p=0.11). CONCLUSIONS: Applying the new definition of HPV positivity, the impact of HPV status on the prognosis of patients irradiated for locally advanced SCCHN was more prominent than in our previous study and associated with all three investigated endpoints.

Ultrafast photo-excitation dynamics in isolated, neutral water clusters.

Using the efficient nonlinear conversion scheme which was recently developed in our group [M. Beutler, M. Ghotbi, F. Noack, and I. V. Hertel, Opt. Lett. 134, 1491 (2010); M. Ghotbi, M. Beutler, and F. Noack, ibid 35, 3492 (2010)] to provide intense sub-50 fs vacuum ultraviolet laser pulses we have performed the first real time study of ultrafast, photo-induced dynamics in the electronically excited Ã-state of water clusters (H(2)O)(n) and (D(2)O)(n) , n=2-10. Three relevant time scales, 1.8-2.5, 10-30, and 50-150 fs, can be distinguished which-guided by the available theoretical results-are attributed to H (D)-ejection, OH (OD) dissociation, and a nonadiabatic transition through a conical intersection, respectively. While a direct quantitative comparison is only very preliminary, the present results provide a crucial test for future modeling of excited state dynamics in water clusters, and should help to unravel some of the many still unresolved puzzles about water.

Two-octave supercontinuum generation in a water-filled photonic crystal fiber.

Supercontinuum generation in a water-filled photonic crystal fiber is reported. By only filling the central hollow core of this fiber with water, the fiber properties are changed such that the air cladding provides broadband guiding. Using a pump wavelength of 1200 nm and few-microjoule pump pulses, the generation of supercontinua with two-octave spectral coverage from 410 to 1640 nm is experimentally demonstrated. Numerical simulations confirm these results, revealing a transition from a soliton-induced mechanism to self-phase modulation dominated spectral broadening with increasing pump power. Compared to supercontinua generated in glass core photonic fibers, the liquid core supercontinua show a higher degree of coherence, and the larger mode field area and the higher damage threshold of the water core enable significantly higher pulse energies of the white light pulses, ranging up to 0.39microJ.

Broadly tunable, sub-30 fs near-infrared pulses from an optical parametric amplifier based on BiB3O6.

We report the generation of tunable femtosecond pulses in the near-IR using a two-stage, white-light seeded, collinear, femtosecond optical parametric amplifier (OPA). The OPA, based on BiB(3)O(6) crystal in both stages and pumped at 800 nm by a 1 kHz Ti:sapphire laser amplifier, provides sub-30 fs signal pulses across the whole tuning range of 1.15-1.6 microm with minimum duration of 22 fs and maximum signal energy of 80 microJ.

Generation of 2.5 µJ vacuum ultraviolet pulses with sub-50 fs duration by noncollinear four-wave mixing in argon.

Generation of sub-50fs vacuum UV pulses with more than 2.5µJ energy at a 1kHz repetition rate is reported. The pulses at 160nm are produced using noncollinear difference-frequency four-wave mixing between the fundamental and third harmonics of an amplified Ti:sapphire laser in argon. While the pulse duration is maintained by increasing the phase-matching pressure, noncollinear interaction improves the conversion efficiency by 1 order of magnitude in comparison with the previous results in collinear geometry.

[Foetal rhabdomyosarcoma with massive cardiac and placental infiltration associated with intrauterine foetal death]. / Zum intrauterinen Fruchttod führendes fetales Rhabdomyosarkom mit ausgeprägter cardialer und placentarer Infiltration.

Rhabdomyosarcoma is a common malignant soft-tissue tumour in children, accounting for 6-7% of all malignant tumours in childhood. Congenital neoplasms are very rare in childhood and represent 2.5% of all paediatric tumours; the intrauterine or congenital diagnosis of rhabdomyosarcomas is extremely seldom. The most frequent locations of rhabdomyosarcomas are the head and neck regions. There are a number of ultrasonographic differential diagnoses. In cases of foetal rhabdomyosarcomas in utero, not only distant metastases but also the possibility of placental infiltration and thus of hypothetical distant metastases in the mother must be taken into consideration because of their metastatic potential. Only very few cases of transplacental penetration of tumour cells and especially of foeto-maternal metastatic invasion, in contrast to materno-foetal tumour cell transfer in the case of maternal cancer disease, have been reported in the literature. We report on a foetal rhabdomyosarcoma of the head and neck area with massive cardiac and placental infiltration associated with intrauterine foetal death in the second trimester. Sonographic features and necropsy findings are described and the differential diagnosis is discussed. Furthermore, diagnostic approaches to rule out a pattern of transplacental metastases are presented.

p53 Mutations in carcinoma of the esophagus and gastroesophageal junction.

BACKGROUND: Recent studies suggested p53 mutations as a prognostic factor. Tumors of the esophagus and gastroesophageal (GE) junction show raising incidence with a general poor prognosis. METHODS: p53 Mutational spectra in 103 patients (68 squamous cell carcinoma/SCC and 35 adenocarcinoma/AC) were compared to clinical and pathologic data. RESULTS AND CONCLUSIONS: p53 Mutations were found in 26 of 68 SSC (38.2%) and in 12 of 35 AC (34.5%). We only found G > T transversions in smokers with SCC. The survival of patients was not affected by p53 mutational status. In our study, the frequency and mutational spectrum of mutant p53 is similar in both histological types without prognostic relevance.

Course and outcome of fetuses suspected of having coarctation of the aorta during gestation.

PURPOSE: To report the course and outcome of a group of fetuses with prenatal suspicion of coarctation of the aorta. MATERIALS AND METHODS: Retrospective observational study in two tertiary fetal cardiology centers between 1993 - 2005. RESULTS: 96 fetuses of whom 52 infants were born alive were studied. Of the 52 liveborn infants, 34 had coarctation of the aorta (65.4 %), thirteen had prenatally diagnosed additional cardiac anomalies (VSD, ASD, aortic and pulmonary stenosis, persistent left superior vena cava) and three were managed as having hypoplastic left heart syndrome. Three neonates had additional extracardiac malformations diagnosed prenatally. 22 neonates underwent surgery, nineteen within the first ten days of life. One neonate only developed clinical signs of coarctation on the fourteenth day of life. The early surgical mortality was three of 22 (13.6 %). The mortality was influenced by prematurity. The survival rate on the basis of intention-to-treat was twenty-nine of 34 neonates with confirmed coarctation (85.3 %). CONCLUSION: Coarctation of aorta during fetal life continues to be a difficult diagnosis. The potential of progressive hypoplasia of left heart structures during gestation in the case of fetal aortic isthmus stenosis with the development of a hypoplastic left heart should be kept in mind and therefore sequential echo-cardiography is recommended during gestation.

[Vasculitis: histopathology and differential diagnosis]. / Vaskulitis: Histopathologie und Differenzialdiagnose.

A histopathologically confirmed biopsy is the gold standard for the diagnosis of vasculitis. Possible etiologies include primary systemic vasculitis, secondary vasculitis or isolated single organ vasculitis, although on histopathological grounds alone a clear differentiation is frequently not possible. The key criteria of morphological vasculitis work-up include vessel size, type of inflammation (granulomatous, necrotizing and/or leukocytoclastic) as well as the presence or absence of immune complexes and extravascular inflammatory changes. Together with the typical organ involvement and serological data, these criteria constitute the basis of vasculitis classification. Differential diagnostic overlaps and possible discrimination methods are presented. In the same way that the clinical approach of vasculitis patients is an interdisciplinary one, histopathology can only provide a definite diagnosis in combination with clinical and serological data. A conclusive morphological diagnosis depends on the right time of biopsy and the selection of appropriate biopsy material.

L1 cell adhesion molecule (L1CAM) as a pathogenetic factor in endometriosis.

BACKGROUND: Endometriosis is a benign and progressive disease with a high prevalence. Women with endometriosis, especially with atypical endometriosis, have a higher probability for developing ovarian cancer compared with women without endometriosis. The L1 cell adhesion molecule (L1CAM) is over expressed in ovarian and endometrial carcinomas and is associated with a bad prognosis. Here, we have analysed L1CAM expression in endometriosis. METHODS AND RESULTS: In our study with the samples from 79 patients with, and 37 patients without, endometriosis, we found that endometriosis cell lines and short-term cultures of endometrium from women with endometriosis expressed L1CAM at the mRNA and protein level. Quantitative RT-PCR analysis showed that L1CAM was expressed at significantly higher level in the epithelial compartment from patients with endometriosis compared with healthy controls (P = 0.0126). By immunohistochemical staining, 15 of 31 ovarian endometriotic lesions (48%) were shown to have L1CAM-positive staining. Of these 15 L1CAM-positive samples, 13 were atypical endometriotic lesions. Soluble L1 present in the conditioned medium of epithelial endometrium cultures from women with endometriosis was able to stimulate neurite outgrowth as measured in a chicken ganglion assay. CONCLUSIONS: We propose that L1CAM could promote endometriosis development by increasing enervation and aggravation. L1CAM expression is higher in atypical endometriosis compared with normal endometriosis.

[How Valid is the Performance Diagnostic in Soccer?]. / Wie valide ist die Leistungsdiagnostik im Fußball?

BACKGROUND: Assessments of physical and physiological performance tests in soccer sports are still unspecific yet. There is also a lack of scientific validation using those as a "golden standard". Concerning match performance a large deficit also exist in sports and medical science. OBJECTIVE: The aim and purpose of this multicentric and prospective diagnostic study was to evaluate the validity of current established and recommended diagnostic tests for endurance and match performance (golden standard: real time of playing) in soccer. MATERIALS AND METHODS: In a prospective study protocol two German soccer teams from the fourth (n = 22) and third (n = 24) national league first underwent different tests of performance and diagnostics ahead of the competition season (tapping, drop jump, counter movement jump, speed dribbling, treadmill running test). Afterwards, match performance of each athlete was assessed by real time of playing (as a surrogate parameter) during the half season (14 and 25 matches). We finally compared test parameters with the match performance in a linear regression analysis. RESULTS: Our analysis showed no statistical relevant relationship between test parameters and match performance (r(2) < 0.10). Only the assessment in maximum of relative oxygen uptake during the treadmill test for endurance was associated with a higher amount of variance (12%). CONCLUSIONS: According to the study results there is no relevant and valid correlation between current established diagnostic tests in soccer sport and sport-specific performance. The time of real engagement during a match might be associated with a quality of performance for the single athlete. Therefore, the assessment of this match activity is the most important parameter for improving diagnostic tests in soccer. The existence of a "golden standard" is essential for validation of any tests and parameters and the development of new specific assessments. At the moment, physical performance tests have no scientific evidence in soccer sports.

2,4,6-Triphenylphosphinine and 2,4,6-triphenylposphabarrelene revisited: synthesis, reactivity and coordination chemistry.

The synthesis of 2,4,6-triphenylphosphinine has been revisited and a general protocol for the preparation of such low-coordinate phosphorus compounds in good to excellent yields could be established. This allows to investigate several aspects of the chemistry of 2,4,6-triarylphosphinine, such as the reaction with in situ generated benzyne to give 2,4,6-triphenylphosphabarrelene. The corresponding 2,4,6-triphenylphosphabarrelene-selenide could be characterized crystallographically for the first time and the structural and electronic properties of this cage-compound in comparison to classical triarylphosphines could be evaluated. Moreover, [(L)W(CO)5)] complexes of both 2,4,6-triphenylphosphinine and 2,4,6-triphenylphosphabarrelene were prepared and characterized by means of X-ray crystallography. This allowed for the first time a direct structural comparison of these related phosphorus compounds, coordinated to the same metal fragment.

NMR relaxation investigation of water mobility in aqueous bovine serum albumin solutions.

T1 and T2 dispersion measurements of proton spin relaxation on aqueous solutions of bovine serum albumin as a function of both protein concentration and temperature, covering Larmor frequencies from 3 kHz to 75 MHz, will be presented as a most conclusive test for a three-phase fast-exchange relaxation model. By means of a computer curve fitting of this model to the experimental data, we were able to separate 3 distinct water environments and, in addition, the rotational tumbling of the bovine serum albumin molecules.