Validation of three BRCA1/2 mutation-carrier probability models Myriad, BRCAPRO and BOADICEA in a population-based series of 183 German families.

Many studies have evaluated the performance of risk assessment models for BRCA1/2 mutation carrier probabilities in different populations, but to our knowledge very few studies have been conducted in the German population so far. In the recent study, we validated the performance of three risk calculation models by names BRCAPRO, Myriad and BOADICEA in 183 German families who had undergone molecular testing of mutations in BRCA1 and BRCA2 with an indication based on clinical criteria regarding their family history of cancer. The sensitivity and specificity at the conventional threshold of 10% as well as for a threshold of 20% were evaluated. The ability to discriminate between carriers and non-carriers was judged by the area under the receiver operating characteristics curve. We further focused on the performance characteristic of these models in patients carrying large genomic rearrangements as a subtype of mutations which is currently gaining increasing importance. BRCAPRO and BOADICEA performed almost equally well in our patient population, but we found a lack of agreement to Myriad. The results obtained from this study were consistent with previously published results from other population and racial/ethnic groups. We suggest using model specific decision thresholds instead of the recommended universal value of 10%. We further suggest integrating the CaGene5 software package, which includes BRCAPRO and Myriad, in the genetic counselling of German families with suspected inherited breast and ovarian cancer because of the good performance of BRCAPRO and the substantial ease of use of this software.

Stereoselective hydrolysis of aryl-substituted dihydropyrimidines by hydantoinases.

In this study, we investigated the possibility of using a modified hydantoinase process for the production of optically pure ß-amino acids. Two aryl-substituted dihydropyrimidines D,L-6-phenyl-5,6-dihydrouracil (PheDU) and para-chloro-D,L-6-phenyl-5,6-dihydrouracil (pClPheDU) were synthesized. Hydrolysis of these novel substrates to the corresponding N-carbamoyl-ß-amino acids by three recombinant D-hydantoinases and several bacterial strains was tested. All applied recombinant D-hydantoinases and eight bacterial isolates catalyzed the conversion of PheDU to N-carbamoyl-ß-phenylalanine (NCßPhe). Some of these biocatalysts showed an enantioselectivity for either the D- or the L-PheDU enantiomer. The second dihydropyrimidinase substrate pClPheDU was hydrolyzed by all three recombinant D-hydantoinases and six of the wild-type strains. To our knowledge, this is the first dihydropyrimidinase activity reported with this aryl-substituted dihydropyrimidine. For selected biocatalysts, hydantoinase activity towards aryl-substituted hydantoins was demonstrated as well. However, none of the bacterial strains tested so far exhibited any carbamoylase activity towards NCßPhe.

Regulation of adhesion behavior of murine macrophage using supported lipid membranes displaying tunable mannose domains.

Highly uniform, strongly correlated domains of synthetically designed lipids can be incorporated into supported lipid membranes. The systematic characterization of membranes displaying a variety of domains revealed that the equilibrium size of domains significantly depends on the length of fluorocarbon chains, which can be quantitatively interpreted within the framework of an equivalent dipole model. A mono-dispersive, narrow size distribution of the domains enables us to treat the inter-domain correlations as two-dimensional colloidal crystallization and calculate the potentials of mean force. The obtained results demonstrated that both size and inter-domain correlation can precisely be controlled by the molecular structures. By coupling α-D-mannose to lipid head groups, we studied the adhesion behavior of the murine macrophage (J774A.1) on supported membranes. Specific adhesion and spreading of macrophages showed a clear dependence on the density of functional lipids. The obtained results suggest that such synthetic lipid domains can be used as a defined platform to study how cells sense the size and distribution of functional molecules during adhesion and spreading.

Assessment of clinical palpation of the axilla as a criterion for performing the sentinel node procedure in breast cancer.

AIMS: Clinically palpable lymph nodes (LNs) are regarded as a contraindication for performing the sentinel node (SN) procedure. Many studies have shown, however, that clinical assessment of axillary LNs is inaccurate. This study evaluated the reliability of clinical axillary LN assessment by experts and assessed whether inaccuracy can be related to LN size. METHODS: Three hundred and one consecutive breast cancer patients undergoing either axillary dissection or SN were studied prospectively. RESULTS: The risk of having metastasis to the LN was 40.4% if the preoperative clinical assessment was "non-palpable LN", 61.5% if the assessment was "palpable but benign LN" and 84.4% if it was "suspicious LN". There were no clinically significant differences in mean size either when the LN was palpable versus non-palpable, or when the LN had metastasis or not. CONCLUSIONS: The clinical assessment of axillary LNs as a criterion for offering the SN procedure is of little value.

Impairment-oriented training or Bobath therapy for severe arm paresis after stroke: a single-blind, multicentre randomized controlled trial.

OBJECTIVE: To study the effects of augmented exercise therapy time for arm rehabilitation as either Bobath therapy or the impairment-oriented training (Arm BASIS training) in stroke patients with arm severe paresis. DESIGN: Single blind, multicentre randomized control trial. SETTING: Three inpatient neurorehabilitation centres. SUBJECTS: Sixty-two anterior circulation ischaemic stroke patients. INTERVENTIONS: Random assignment to three group: (A) no augmented exercise therapy time, (B) augmented exercise therapy time as Bobath therapy and (C) augmented exercise therapy time as Arm BASIS training. MAIN OUTCOME MEASURE: Fugl-Meyer arm motor score. Secondary measure: Action Research Arm Test (ARA). Ancillary measures: Fugl-Meyer arm sensation and joint motion/pain scores and the Ashworth Scale (elbow flexors). RESULTS: An overall effect of augmented exercise therapy time on Fugl-Meyer scores after four weeks was not corroborated (mean and 95% confidence interval (CI) of change scores: no augmented exercise therapy time (n=20) 8.8, 5.2-12.3; augmented exercise therapy time (n=40) 9.9, 6.8-13.9; p = 0.2657). The group who received the augmented exercise therapy time as Arm BASIS training (n=20) had, however, higher gains than the group receiving the augmented exercise therapy time as Bobath therapy (n=20) (mean and 95% CI of change scores: Bobath 7.2, 2.6-11.8; BASIS 12.6, 8.4-16.8; p = 0.0432). Passive joint motion/pain deteriorated less in the group who received BASIS training (mean and 95% CI of change scores: Bobath -3.2, -5.2 to -1.1; BASIS 0.1, -1.8-2.0; p = 0.0090). ARA, Fugl-Meyer arm sensation, and Ashworth Scale scores were not differentially affected. CONCLUSIONS: The augmented exercise therapy time as Arm BASIS training enhanced selective motor control. Type of training was more relevant for recovery of motor control than therapeutic time spent.

[Telephone surveys. Advantages and drawbacks]. / Telefonsurveys Vor- und Nachteile.

Telephone surveys have gained considerable importance in recent years. The present article describes advantages and drawbacks of this mode of data collection. Particular attention is devoted to a number of aspects involved: costs, computer-assisted fieldwork, response rates, special demands on sampling, use of incentives, survey participation and the role of telephone surveys in flexible mixed-mode survey designs. A concluding section offers some practical recommendations on carrying out telephone surveys.

Amphetamine fails to facilitate motor performance and to enhance motor recovery among stroke patients with mild arm paresis: interim analysis and termination of a double blind, randomised, placebo-controlled trial.

PURPOSE: To assess the effects of d-amphetamine on motor facilitation and recovery in stroke patients with mild arm paresis receiving the Arm Ability training. METHODS: Thirty-one stroke patients with mild arm paresis were randomly assigned to either (a.) receiving placebo or (b.) d-amphetamine twice a week 2 hours before Arm Ability training sessions for three weeks. MAIN OUTCOME MEASURE: time needed to perform TEMPA tasks, a measure of upper extremity performance reflecting everyday life tasks. Secondary measures: aimed movements, tapping, and a 10 m walkway as well as motor performance during training sessions. RESULTS: The interim efficacy analysis of 26 stroke patients who completed the study intervention showed overall arm motor recovery both from pre to post test after 3 weeks of training and from pre test to follow-up 1 year later. No superior effect of d-amphetamine over placebo could be substantiated for either motor facilitation during training or motor recovery (post training or long-term). D-amphetamine exerted mild effects on blood pressure. Serious adverse events were not observed. CONCLUSIONS: d-Amphetamine failed to facilitate motor performance during training sessions, to promote skill acquisition with training tasks, and most importantly to enhance motor recovery among patients with mild arm paresis after stroke.

False-negative frozen section of sentinel lymph node biopsy for breast cancer.

A prospective study is presented of frozen section examinations (FS) performed in parallel with 265 consecutive sentinel lymph node procedures (SLNP) over a 20-month period. The final pathological study included immunohistochemistry (IHC) for keratin if the haematoxylin-eosin (HE)-stained section was tumour free. FS correctly identified node-positive or node-negative axillae in 235 cases. In 28 SLNPs the final examination gave a positive result not detected in the FS, resulting in reoperation. In 21 of these false-negative (FN) cases micrometastases (MIM) were present. There were no false-positive cases, but in two cases of lobular carcinoma the findings in the FS were equivocal, the final reports recording metastases in one but not in the other. Lobular carcinoma and other less common subtypes of carcinoma were overrepresented, ductal carcinoma not otherwise specified (NOS) being less likely to affect the FN findings.