Mutations of the ret protooncogene in German multiple endocrine neoplasia families: Relation between genotype and phenotype.

It has been suggested that not only the position but also the nature of the mutations of the ret protooncogene strongly correlate with the clinical manifestation of the multiple endocrine neoplasm type 2 (MEN 2) syndrome. In particular, individuals with a Cys634-Arg substitution should have a greater risk of developing parathyroid disease. We, therefore, analyzed 94 unrelated families from Germany with inherited medullary thyroid carcinoma (MTC) for mutation of the ret protooncogene. In all but 1 of 59 families with MEN 2A, germline mutations in the extracellular domain of the ret protein were found. Some 81% of the MEN 2A mutations affected codon 634. Phenotype-genotype correlations suggested that the prevalence of pheochromocytoma and hyperparathyroidism is significantly higher in families with codon 634 mutations, but there was no correlation with the nature of the mutation. In all but 1 of 27 familial MTC (FMTC) families, mutations were detected in 1 of 4 cysteines in the extracellular domain of the ret protooncogene. Half of the FMTC mutations affected codon 634. Mutations outside of codon 634 occurred more often in FMTC families than in MEN 2A families. In all but 1 of 8 MEN 2B patients, de novo mutations in codon 918 were found. These data confirm the preferential localization of MEN 2-associated mutations and the correlation between disease phenotype and the position of the ret mutation, but there was no correlation between the occurrence of hyperparathyroidism or pheochromocytoma and the nature of the mutation

Do all roads lead to rome? The potential of different approaches to diagnose Aelurostrongylus abstrusus infection in cats

An infection with the cat lungworm, Aelurostrongylus abstrusus, can be subclinical, but it can also cause severe respiratory clinical signs. Larvae excretion, antibody levels, clinical assessment findings of the respiratory system and diagnostic imaging findings were recorded and compared for six cats with experimental aelurostrongylosis. In five cats, patency started 33–47 days post infection (pi), but two cats excreted larvae only in long intervals and low numbers. Positive ELISA results were observed in four cats with patent aelurostrongylosis, starting between five days before and 85 days after onset of patency. One seropositive cat remained copromicroscopically negative. Mild respiratory signs were observed in all cats examined. A computed tomographic (CT) examination of the lungs displayed distinct alterations, even in absence of evident clinical signs or when larvae excretion was low or negative. The thoracic radiograph evaluation correlated with the CT results, but CT was more distinctive. After anthelmintic treatment in the 25th week post infection, pulmonary imaging findings improved back to normal within 6–24 weeks. This study shows that a multifaceted approach, including diagnostic imaging, can provide a clearer diagnosis and monitoring of disease progression. Furthermore, a CT examination provides an alternative to post mortem examination and worm counts in anthelmintic efficacy studies

Identification of occult metastases of medullary thyroid carcinoma by pentagastrin-stimulated intravenous calcitonin sampling followed by targeted surgery

BACKGROUND: High calcitonin (CT) serum levels suggest metastatic spread in medullary thyroid carcinoma (MTC) after thyroidectomy. In limited disease stages, however, morphological investigations including ultrasound, magnetic resonance imaging (MRI) and 18F-FDG positron emission tomography ([18F]FDG-PET) may often fail to identify exact tumour sites. OBJECTIVE: The aim of the present study was to establish an improved strategy to identify small cervical tumours by combining pentagastrin stimulation with bilateral cervical intravenous CT sampling followed by high-resolution ultrasound. DESIGN AND PATIENTS: Six MTC patients were examined, of whom five patients already had bilateral neck dissection. Five patients had sporadic MTC, and one patient suffered from MEN2a. RESULTS: Retrospective analysis of all patients revealed a highly sensitive positive correlation between an early calcitonin peak (20–40 s after pentagastrin injection) and site of cervical tumour affection. Postinterventional ultrasound examination of the affected regions of the neck revealed suspicious presence; in some cases small lymph nodes of less than 1 cm in size were then surgically excised. On histology, small tumours could be identified in four patients. Postsurgical examination revealed a clear decline of basal serum calcitonin levels in four patients (between −41% and −100%). In two patients CT normalized to baseline levels (< 10 pg/ml) and in another two patients CT rendered to near normal (14 and 17 pg/ml). CONCLUSION: Pentagastrin stimulation-based intravenous catheter sampling may be beneficial in the diagnostic work-up of MTC after thyroidectomy. Our data show that an early calcitonin peak (20–40 s after administration of pentagastrin) helps to identify tumour-affected regions

A Spectacular VHE Gamma-Ray Outburst from PKS 2155-304 in 2006

Since 2002 the VHE (>100 GeV) gamma-ray flux of the high-frequency peaked BL Lac PKS 2155-304 has been monitored with the High Energy Stereoscopic System (HESS). An extreme gamma-ray outburst was detected in the early hours of July 28, 2006 (MJD 53944). The average flux above 200 GeV observed during this outburst is ~7 times the flux observed from the Crab Nebula above the same threshold. Peak fluxes are measured with one-minute time scale resolution at more than twice this average value. Variability is seen up to ~600 s in the Fourier power spectrum, and well-resolved bursts varying on time scales of ~200 seconds are observed. There are no strong indications for spectral variability within the data. Assuming the emission region has a size comparable to the Schwarzschild radius of a ~10^9 solar mass black hole, Doppler factors greater than 100 are required to accommodate the observed variability time scales.Comment: 4 pages, 3 figures; To appear in the Proceedings of the 30th ICRC (Merida, Mexico

Pain severity predicts depressive symptoms over and above individual illnesses and multimorbidity in older adults.

BACKGROUND: Multi-morbidity in older adults is commonly associated with depressed mood. Similarly, subjective reports of pain are also associated with both physical illness and increased depressive symptoms. However, whether pain independently contributes to the experience of depression in older people with multi-morbidity has not been studied. METHODS: In this study, participants were 1281 consecutive older adults presenting to one of 19 primary care services in Australia (recruitment rate = 75%). Participants were asked to indicate the presence of a number of common chronic illnesses, to rate their current pain severity and to complete the Geriatric Depression Scale. RESULTS: Results confirmed that the number of medical illnesses reported was strongly associated with depressive symptoms. Twenty-six percent of participants with multi-morbidity scored in the clinical range for depressive symptoms in comparison to 15% of participants with no illnesses or a single illness. In regression analyses, the presence of chronic pain (t = 5.969, p < 0.0005), diabetes (t = 4.309, p < 0.0005), respiratory (t = 3.720, p < 0.0005) or neurological illness (t = 2.701, p = 0.007) were all independent contributors to depressive symptoms. Even when controlling for each individual illness, and the overall number of illnesses (t = 2.207, p = 0.028), pain severity remained an independent predictor of depressed mood (F change = 28.866, p < 0.0005, t = 5.373, p < 0.0005). CONCLUSIONS: Physicians should consider screening for mood problems amongst those with multi-morbidity, particularly those who experience pain

Anwendung der mathematischen Optimierung bei der physikalisch und geometrisch nichtlinearen Analyse und Bemessung seismisch beanspruchter Tragwerke

Moderne Bemessungskonzepte für seismisch beanspruchte Hochbauten, wie die Methode der Kapazitäts-bemessung, planen inelastisches Verhalten einzelner Bereiche der Konstruktion beim Entwurf bewußt ein, um so einen Teil der durch das Beben eingetragenen Energie als inelastische Formänderungsarbeit zu absorbieren. Wird bei Akzeptanz inelastischen Verhaltens eine bestimmte Belastungsintensität, die als adaptive Grenzlast oder Einspiellast bezeichnet wird, überschritten, kann es infolge zyklischer Einwirkungen zu einer unbe-grenzten Akkumulation inelastischer Deformationen kommen. Die adaptive Grenzlast stellt damit für zyklische Einwirkungen eine geeignete Kenngröße zur Bewertung der Tragwerksqualität dar, bei der neben der Sicherung des Gleichgewichts ein bestimmtes Schädigungsniveau nicht überschritten wird. Im vorliegenden Beitrag werden die Grundzüge eines Bemessungs- und Nachweiskonzeptes für seismisch beanspruchte Stahlbetontragwerke, das unter Einbeziehung der Grundprinzipe der Kapazitätsbemessung von einem einheitlichen Kriterium zur Beschreibung des Grenzzustandes der Tragfähigkeit auf der Basis der adaptive Grenzlast ausgeht, vorgestellt. Dabei ist die Abschätzung der Verformungen notwendiger Bestandteil des Nachweis- bzw. Bemessungskonzeptes. Bei Druckgliedern ist die Berücksichtigung des Einflusses der Verformungen notwendiger Bestandteil des Bemessungskonzeptes. Entsprechende Erweiterungen der Berechnungsmodelle zur Berücksichtigung des Einflusses geometrisch nichtlinearer Effekte im Sinne einer Theorie II. Ordnung werden vorgestellt

Dark matter powered stars: Constraints from the extragalactic background light

The existence of predominantly cold non-baryonic dark matter is unambiguously demonstrated by several observations (e.g., structure formation, big bang nucleosynthesis, gravitational lensing, and rotational curves of spiral galaxies). A candidate well motivated by particle physics is a weakly interacting massive particle (WIMP). Self-annihilating WIMPs would affect the stellar evolution especially in the early universe. Stars powered by self-annihilating WIMP dark matter should possess different properties compared with standard stars. While a direct detection of such dark matter powered stars seems very challenging, their cumulative emission might leave an imprint in the diffuse metagalactic radiation fields, in particular in the mid-infrared part of the electromagnetic spectrum. In this work the possible contributions of dark matter powered stars (dark stars; DSs) to the extragalactic background light (EBL) are calculated. It is shown that existing data and limits of the EBL intensity can already be used to rule out some DS parameter sets.Comment: Accepted for publication in ApJ; 7 pages, 5 figure