Dynamic MR imaging of breast lesions: correlation with microvessel distribution pattern and histologic characteristics of prognosis.

To evaluate the association of dynamic enhancement parameters of benign and malignant breast lesions at magnetic resonance (MR) imaging with microvessel distribution and histologic prognostic tumor characteristics.Regional review board approval and informed consent were obtained. Surgical resection specimens of breast lesions (32 benign, 86 malignant) in 118 patients (age range, 28-86 years; mean, 58 years) who had undergone dynamic T1-weighted MR imaging of both breasts were included in the study. Different MR enhancement parameters and microvessel density (MVD) distribution were determined. In malignant lesions, TNM stage, tumor grade, proliferative activity, and hormone receptor expressi…

Sympathetic Vasomotor Response of the Radial Artery in Patients With Diabetic Foot Syndrome

OBJECTIVE—Neurophysiological assessment of the peripheral autonomic system is characterized by various limitations. An alternative approach to laser Doppler and venous plethymography is the assessment of the sympathetic vasomotor response of the radial artery obtained by continuous wave Doppler sonography. Nomogram data have been established and demonstrate the temporary disappearance of diastolic flow after coughing or deep inspiration. RESEARCH DESIGN AND METHODS—We assessed the sympathetic vasomotor response in 25 patients (mean age 64 years, range 43–76) with diabetic foot syndrome. The Doppler data were correlated with nerve conduction studies of the median and peroneal nerve, the exte…

A case control study of statin and magnesium administration in patients after aneurysmal subarachnoid hemorrhage: incidence of delayed cerebral ischemia and mortality

To analyse the effect of the implementation of statin and magnesium treatment on delayed cerebral ischemia (DCI) and 14 day mortality in patients with subarachnoid hemorrhage (SAH).Retrospective, single-center, observational case control study. One hundred SAH patients received either simvastatin and magnesium, solely statin or no treatment.Eighteen percent (n=5) of patients receiving statin and magnesium treatment developed a DCI whereas 24% (n=5) in the statin group and 16% (n=8) in the control group had DCI. Dead by day 14 was registered in 18% (n=5) of patients in the statin and magnesium group, in 10% (n=2) in the statin group and in 27% (n=14) in the control group. None of the results…

Response to transarterial chemoembolization as a biological selection criterion for liver transplantation in hepatocellular carcinoma.

Criteria to select patients with hepatocellular carcinoma (HCC) for liver transplantation (LT) are based on tumor size and number of nodules rather than on tumor biology. The present study was undertaken to assess the role of transarterial chemoembolization (TACE) in selecting patients with tumors suitable for LT. Ninety-six consecutive patients with HCC were treated by repeatedly performed TACE, 62 of them exceeding the Milan criteria. Patients meeting the Milan criteria were immediately listed, and patients beyond the listing criteria were listed upon downstaging of the tumor following successful TACE. Fifty patients were finally transplanted. Of these 50 patients, 34 exceeded the Milan c…

Prognostic factors and outcomes of patients with hepatocellular carcinoma in non-cirrhotic liver

To report the outcome of patients with hepatocellular carcinoma (HCC) in non-cirrhotic liver depending on the mode of primary treatment and to define clinicopathological factors influencing patients' prognosis.A retrospective analysis of an unselected cohort of 105 patients was performed. Overall survival (OS) was estimated by the Kaplan-Meier method and potentially prognostic factors were analyzed in Cox regression models.OS of the whole cohort at 1, 3, and 5 years was 66%, 47%, and 29%, respectively. Tobacco consumption, ECOG0, macroscopic vascular invasion, continuous tumor diameter, and treatment other than resection were predictors of decreased OS in the whole cohort. Resection was per…

Impact of several histopathological prognosticators and local tumour extension on oncological outcome in pT3b/c N0M0 renal cell carcinoma.

OBJECTIVE To investigate the prognostic relevance of different histopathological features and local tumour extension in patients with pT3b/c N0M0 renal cell carcinoma (RCC), as recently new proposals of reclassifying tumour fat invasion in pT3b/c RCC have been made but the effect of other histopathological tumour characteristics and combinations thereof with tumour invasion has yet to be determined in these patients. PATIENTS AND METHODS Between 1990 and 2006, 1943 patients underwent surgical treatment for renal tumours in our institution, of which 175 patients (8.7%) had pT3b/c RCC. After exclusion of 57 patients (32.6%) with lymph node and/or distant metastases at the time of diagnosis, 1…

A genetic basis for IFN-gamma production and T-bet expression in humans.

Abstract Th1 and Th2 cytokines secreted by polarized effector T cells play a pivotal role in the development of autoimmune and allergic diseases. However, the genetic basis of cytokine production by T lymphocytes in humans is poorly understood. In this study, we investigated the genetic contribution to cytokine production and regulation of T cell-specific transcription factors in a prospective twin study. We found a substantial genetic contribution to the production of Th1 cytokines such as IFN-γ and TNF-α with heritabilities of 0.85 (95% confidence intervals, 0.74–0.95) and 0.72 (0.50–0.93), respectively, whereas no genetic influence on production of the Th2 signature cytokine IL-4 was obs…

Transient evoked otoacoustic emissions in vestibular neuritis.

Objectives: Partial or total degeneration of the vestibulocochlear anastomosis at its takeoff from the saccular ganglion and regenerating efferent neural buds under the cochlear outer hair cells (OHCs) have been found in the temporal bones of human patients with a history of vestibular neuritis (VN). We sought to test whether VN has any functional impact on the ipsilateral OHCs by means of transient evoked otoacoustic emission (TEOAE) testing. Methods: We retrospectively analyzed prospectively collected TEOAE data of 28 patients (19 female, 9 male; age range, 21 to 60 years; median age, 42.5 years). The pure tone air conduction hearing thresholds at each standard audiometric frequency (0.12…

Comparison of electronystagmography results with dynamic posturography findings in patients with vestibular schwannoma.

Condition-5-score (C5S) and condition-6-score (C6S) of computerized dynamic platform posturography (CDPP) can detect the presence of a functional deficit of the lateral semicircular canal (and the superior vestibular nerve), irrespective of the central vestibular compensatory status, in vestibular schwannoma (VS) patients.To test whether CDPP findings differ between VS patients with and without asymmetry on caloric and/or rotational ENG studies.This was a retrospective review of 216 consecutive patients with VS. C5S and C6S of CDPP (Equitest) were compared among patients with normal caloric and rotational studies, patients with asymmetry on caloric studies and normal rotational studies, and…

C4A deficiency and nonresponse to hepatitis B vaccination

Hepatitis B vaccination failure has been linked to the presence of certain human leukocyte antigen class II alleles. However, the functional background of these associations has remained unclear. Complement component C 4 is encoded within the major histocompatibility complex and is essential for classical pathway activation.Healthy individuals (n=4269) were vaccinated in a prospective trial with Engerix B. Nonresponse was classified as anti-HBs10 U/l after the last vaccination. Seventy-three nonresponders (NR) (1.7%) were identified. For comparison 53 responders (R) (anti-HBs10 IU/l) were drawn randomly from the same cohort. C4 allotyping was carried out by high-voltage agarose gel electrop…

Manifestationen der Atherosklerose in verschiedenen Gefäßregionen

Aus pathologischen Untersuchungen ist bekannt, dass es sich bei der Atherosklerose um eine Erkrankung handelt, die den gesamten Gefasbaum betrifft. In der Framingham-Studie wurden Risikofaktoren der Atherosklerose ermittelt, die fur die Lokalisation der Atherosklerose in verschiedenen Gefasprovinzen eine unterschiedliche Wertigkeit besitzen. Patienten mit Manifestationen der Atherosklerose in Herz-, Hals- und Beinschlagadern haben im Vergleich zu einem Normalkollektiv eine schlechtere Prognose. Auserdem liegt eine hohe Koinzidenz von atherosklerotischen Lasionen in den verschiedenen Gefasregionen vor. Besonders ungunstig ist die Prognose fur Patienten, die zum Zeitpunkt der Untersuchung ber…

Multiple testing in candidate gene situations: a comparison of classical, discrete, and resampling-based procedures.

In candidate gene association studies, usually several elementary hypotheses are tested simultaneously using one particular set of data. The data normally consist of partly correlated SNP information. Every SNP can be tested for association with the disease, e.g., using the Cochran-Armitage test for trend. To account for the multiplicity of the test situation, different types of multiple testing procedures have been proposed. The question arises whether procedures taking into account the discreteness of the situation show a benefit especially in case of correlated data. We empirically evaluate several different multiple testing procedures via simulation studies using simulated correlated SN…

Genetic and environmental influences on the fibrinolytic system: a twin study.

SummaryThe determination of heritability is a key issue to assess the predictive power of polymorphisms for disease in clinical studies. The aim of this study was to determine the heritability of proteins and activation markers of the fibrinolytic system in a large cohort of healthy twins. Heritability was calculated as 0.76 for thrombin activatable fibrinolysis inhibitor (TAFI), 0.44 for plasminogen activator inhibitor-1 (PAI-1), and 0.43 for tissue plasminogen activator. No significant genetic influence was observed for α2-antiplasmin-plasmin-complex and D-dimer. Heritability explained by single gene polymorphisms was 25.2% for TAFI 505G>A, 31.5% for 1542C>G, and 50.0% for combinati…

Intratympanic Dexamethasone and Hyaluronic Acid in Patients with Low-Frequency and Ménière's-Associated Sudden Sensorineural Hearing Loss

Steroids are widely used for the treatment of cochleovestibular disorders. Direct steroid application in the middle ear cavity, when combined with a round window membrane permeability-modulating substance, increases the level of the steroid reaching the target cells. We measured hearing in patients with idiopathic isolated low-frequency sensorineural hearing loss and in patients with sudden sensorineural hearing loss and a history of Ménière's disease. Contradictory reports about effectiveness of intratympanic steroid therapy on vertigo control and hearing improvement in patients with Ménière's disease exist in the literature.Eighteen patients with isolated low-frequency idiopathic sudden s…

Long-term outcome prediction by clinicopathological risk classification algorithms in node-negative breast cancer--comparison between Adjuvant!, St Gallen, and a novel risk algorithm used in the prospective randomized Node-Negative-Breast Cancer-3 (NNBC-3) trial.

Background: Defining risk categories in breast cancer is of considerable clinical significance. We have developed a novel risk classification algorithm and compared its prognostic utility to the Web-based tool Adjuvant! and to the St Gallen risk classification. Patients and methods: After a median follow-up of 10 years, we retrospectively analyzed 410 consecutive node-negative breast cancer patients who had not received adjuvant systemic therapy. High risk was defined by any of the following criteria: (i) age 2 cm. All patients were also characterized using Adjuvant! and the St Gallen 2007 risk categories. We analyzed disease-free survival (DFS) and overall survival (OS). Results: The Node-…

Usefulness of combining clinical and radiological dental findings for a more accurate noninvasive age estimation.

: The aim of this study was to establish correlations of clinical and radiological dental findings, alone or in combination, with chronological age in adults. Dental findings and orthopantomograms of 984 patients (aged 20–60 years; 524 females/460 males) were analyzed. DMF-T index and distance (alveolar bone level, ABL) between cemento-enamel junction and alveolar bone margin were recorded. Additionally, clinical and radiological findings at each tooth crown and root were collected according to the actual status of destruction and restoration, and a total score for each dentition (TSD) was calculated. After univariate correlation analysis, correlation coefficients for ABL and TSD were impro…

Discrimination of early/intermediate and advanced/complicated coronary plaque types by radiofrequency intravascular ultrasound analysis

Radiofrequency intravascular ultrasound (IVUS-RF) analysis, as an extension of conventional IVUS imaging, may provide more accurate plaque discrimination. Thirty-two autopsy atherosclerotic coronary arteries were investigated. Corresponding sectors in different plaques were matched by histologic and RF analysis. Histologic analysis utilized the American Heart Association plaque classification. The backscattered ultrasound RF signal was analyzed by fast-Fourier transform, providing the underlying frequency components of its power spectrum. The normalized backscattered signal power (in decibels [dB]) for frequencies between 15.3 and 40.3 MHz was then measured for plaque discrimination. Advanc…

Association analysis of SCN9A gene variants with borderline personality disorder

Borderline personality disorder (BPD) is a serious psychiatric disorder affecting about 1-2% of the general population. Key features of BPD are emotional instability, strong impulsivity, repeated self-injurious behavior (SIB) and dissociation. In the etiology of BPD and its predominant symptoms, genetic factors have been suggested. The voltage-gated sodium channel Nav1.7 is expressed in sensory neurons and in the hippocampus, a key region of the limbic system probably dysfunctional in BPD and dissociative disorders. The alpha-subunit of Nav1.7 is encoded by the SCN9A gene on chromosome 2 and variations of SCN9A can lead to complete inability to sense pain. The aim of the present study was t…

Incidence of HAV and HBV infections and vaccination rates in patients with autoimmune liver diseases.

Hepatitis A virus (HAV) or hepatitis B virus (HBV) superinfection is associated with an increased mortality in patients with chronic liver diseases (CLD). Despite official recommendations, it was reported that the vaccination rate against HAV is low in patients with chronic hepatitis C infection. To evaluate the situation in patients with autoimmune liver diseases, we conducted a retrospective cohort study.Susceptibility to HAV and HBV infections, course of HAV and HBV infections, vaccination rates against HAV and HBV, and efficacy of hepatitis A/B vaccines were evaluated by antibody testing in 225 patients with autoimmune liver diseases during 1,677 person-years.Susceptibility to HAV/HBV i…

Effects of combined therapy of clopidogrel and aspirin in preventing thrombus formation on mechanical heart valves in an ex vivo rabbit model.

Abstract Background: The aim of our study was to investigate the efficacy of the combination of clopidogrel and aspirin in the prevention of thrombus formation on artificial heart valves in an experimental rabbit model as compared to anticoagulation with warfarin. Methods: Studies were performed after oral administration of clopidogrel and aspirin in group I (n=9) for 5 days, after 5±2 days treatment with warfarin in group II (n=9) and without medication in group III (n=9). Leaflets from Sulzer Carbomedics bileaflet valves were placed in a flow chamber. The flow chamber was filled with blood in a continuous circulation between the carotid artery and the jugular vein. Results: In group III, …

Expression of multiple epigenetically regulated cancer/germline genes in nonsmall cell lung cancer.

Cancer/germline (CG) antigens represent promising targets for widely applicable mono- and multiantigen cancer vaccines for nonsmall cell lung cancer (NSCLC). Since little is known about their composite expression in this tumor type, we analyzed 7 CG genes (MAGE-A3, NY-ESO-1, LAGE-1, BRDT, HOM-TES-85, TPX-1 and LDHC) in 102 human NSCLC specimens. About 81% of NSCLC express at least 1 and half of the specimen at least 2 CG genes. Activation of most of these genes occurs more frequently in squamous cell cancer than in adenocarcinomas. Even though we found all genes but one to be regulated by genomic methylation, not all of them are co-expressed. In particular, combining CG genes not localized …

Genetic and environmental contributions to plasma C-reactive protein and interleukin-6 levels--a study in twins.

Elevated baseline levels of acute-phase proteins such as C-reactive protein (CRP) or cytokines like interleukin-6 (IL-6) are known risk factors for atherosclerosis and cardiovascular disease (CVD) events. However, until today, there is only controversial information about the contribution of genetic and environmental factors. Therefore, we performed an open prospective study in 108 monozygotic (MZ) and 60 same-sex dizygotic (DZ) twin pairs to analyse the genetic and environmental contributions to plasma CRP and IL-6 levels. Heritability of IL-6 was 0.61, indicating that plasma IL-6 levels are to a major part influenced by genetic determinants; however, for CRP, heritability was only 0.22, p…

Interaction between gene variants of the serotonin transporter promoter region (5-HTTLPR) and catecholO-methyltransferase (COMT) in borderline personality disorder

Borderline personality disorder (BPD) is characterized by a heterogeneous symptomatology with instability in impulse control, interpersonal relationships and self-image. BPD patients display repeated self-injury, chronic suicidal tendencies and emotional dysregulation, mainly dysregulation of negative affect. In its etiology, genetic and environmental factors have been suggested. Recently, an investigation in male healthy volunteers found gene–gene effects of the catechol-O-methyl-transferase (COMT) low-activity (Met158) and the low-expression allele of the deletion/insertion (short/long or S/L, respectively) polymorphism in the serotonin transporter-linked promoter region (5-HTTLPR) on the…

Searching for Gene Expression Differences in Primary Fibroblasts Between Patients with One and Two Neoplasms in Childhood

Genetic factors are important for developing primary and subsequent malignancies in children. This study investigated the role of genetic factors involved in DNA-repair. Designed as a feasibility study, it addressed the possibility of obtaining samples for genetic analyses from former patients through the German Childhood Cancer Registry. Testing feasibility was as important as the biological question itself. We analyzed the expression of DNA-repair genes in untreated primary fibroblasts of 20 individuals with a second neoplasm compared to 20 matched single neoplasm cases using customized cDNA microarrays (1344 gene sequences, about 800 genes). Matching was by first neoplasm, age, and year …

Dynamic posturography findings predict balance status in vestibular schwannoma patients.

OBJECTIVE To test whether condition 5 score (C5S) and condition 6 score (C6S) of the sensory organization test of computerized dynamic platform posturography (CDPP) differ between vestibular schwannoma (VS) patients with and without vestibular symptoms. STUDY DESIGN Retrospective review of prospectively collected data. SETTING Tertiary academic referral center. PATIENTS Two hundred and sixteen consecutive patients with a histological diagnosis of a VS (103 women; 113 men; age range, 18-78 years; median, 54 years) who had been preoperatively evaluated by CDPP. A hundred and twelve patients had a history of vertigo, dizziness, and/or imbalance, and 104 patients had neither present nor past ve…

Role of the progesterone receptor for paclitaxel resistance in primary breast cancer

Paclitaxel plays an important role in the treatment of primary breast cancer. However, a substantial proportion of patients treated with paclitaxel does not appear to derive any benefit from this therapy. We performed a prospective study using tumour cells isolated from 50 primary breast carcinomas. Sensitivity of primary tumour cells to paclitaxel was determined in a clinically relevant range of concentrations (0.85-27.2 microg ml(-1) paclitaxel) using an ATP assay. Chemosensitivity data were used to study a possible association with immunohistochemically determined oestrogen and progesterone receptor (ER and PR) status, as well as histopathological parameters. Progesterone receptor (PR) m…

Abstract 5504: Second neoplasms after childhood cancer and gene expression differences in primary fibroblasts

Abstract Treatment of the primary neoplasm with radiotherapy or chemotherapy is an established risk factor for second neoplasms (SNs) after childhood cancer. As only a small percentage of the treated children suffer from SN, other shared risk factors must be involved. A predisposition for the occurrence of a SN might be a pre-existing somatic genetic defect associated with DNA repair. We investigated the association between gene expression involved in DNA-repair and the development of SNs after childhood cancer. Designed as a feasibility study this project addressed the possibility of obtaining samples for genetic analyses from former patients through the German Childhood Cancer Registry. W…

Impact of infectious burden on extent and long-term prognosis of atherosclerosis.

Background — Recent findings suggest a causative role of infections in the pathogenesis of atherosclerosis. In hypothesizing an association between infectious agents and the development of atherosclerosis, we would expect a correlation to the extent of atherosclerosis. Moreover, this effect could be multiplied by the number of pathogens to which an individual had been exposed. Methods and Results — In 572 patients, IgG or IgA antibodies to herpes simplex virus 1 and 2, cytomegalovirus, Epstein-Barr virus, Hemophilus influenzae , Chlamydia pneumoniae , Mycoplasma pneumoniae , and Helicobacter pylori were measured. The extent of atherosclerosis was determined by coronary angiography, carotid…

Impact of infectious burden on progression of carotid atherosclerosis.

Background and Purpose— Recent findings suggest a causative role of infections in the pathogenesis of atherosclerosis. The extent of atherosclerosis and the prognosis of patients with atherosclerosis seem to be increased by the number of infections to which an individual has been exposed. In a prospective study, we evaluated the effect of 8 pathogens and the aggregate pathogen burden on the progression of carotid atherosclerosis. Methods— In 504 patients (74.9% men; age, 62.9±10 years), we measured intima-media thickness and prevalence of carotid artery stenosis. Follow-up measurements after a mean of 2.5 years were available in 427 patients (85%). Blood samples were taken, and IgG or IgA …

S36.4: Control of false discovery rate in adaptive designs

Cochlear origin of early hearing loss in vestibular schwannoma.

Objective: To test whether early hearing loss (HL) is cochlear in origin in patients with vestibular schwannoma (VS). Study Design: Retrospective case review in an academic tertiary referral center. Methods: A group of 19 VS patients with normal/symmetrical hearing and a group of 20 VS patients with mild HL (threshold at any tested frequency better than 45 dB HL) on the tumor ear side. Differences of the amplitudes of the distortion products of otoacoustic emissions (DPOAEs) between the tumor ear and the nontumor ear were studied at frequencies of 1, 1.4, 2, 2.8, and 4 kHz. The Wilcoxon test was used to compare the ears for both groups and to test for possible differences in tumor size betw…

Einfluss eines gest�rten Glukosestoffwechsels auf Manifestationen und Prognose der Atherosklerose in verschiedenen Gef��regionen

Patienten mit kardiovaskularen Erkrankungen haben eine deutlich schlechtere Prognose, wenn ein Diabetes mellitus (DM) vorliegt. Bereits bei Vorliegen eines abnormalen Nuchternglukosewertes ist die Inzidenz kardiovaskularer Ereignisse erhoht. Ziel dieser Untersuchung war es, den Einfluss diabetischer Stoffwechselstorungen auf die Inzidenz atherosklerotischer Manifestationen und auf die Langzeitprognose von Patienten mit Atherosklerose in multiplen Gefasregionen zu erfassen. Wir schlossen 906 Patienten (73% Manner, mittleres Alter 62,5 ± 9 Jahre) vor geplanter Koronarangiographie prospektiv in die Untersuchung ein. Bei allen Patienten wurde der periphere Gefasstatus mittels Duplexsonographie …