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

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

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

Broadband multi-wavelength campaign on PKS 2005-489

The spectral energy distribution (SED) of high-frequency peaked BL Lac objects (HBL) is characterized by two peaks: one in the UV-X-ray and one in the GeV-TeV regime. An interesting object for analyzing these broadband characteristics is PKS 2005-489, which in 2004 showed the softest TeV spectrum ever measured. In 2009, a multi-wavelength campaign has been conducted with, for the first time, simultaneous observations by H.E.S.S. (TeV), Fermi/LAT (GeV), RXTE (keV), Swift (keV, UV, optical) and ATOM (optical) to cover the two peaks of the SED. During this campaign PKS 2005-489 underwent a high state in all wavebands which gives the opportunity to study in detail the emission processes of a high state of this interesting HBL.Comment: 2009 Fermi Symposium; eConf Proceedings C09112

Induced polarization of Lambda(1116) in kaon electroproduction

We have measured. the induced polarization of the Lambda(1116) in the reaction ep - \u3e e\u27 K+ Lambda, detecting the scattered e\u27 and K+ in the final state along with the proton from the decay Lambda - \u3e p pi(-). The present study used the CEBAF Large Acceptance Spectrometer (CLAS), which allowed for a large kinematic acceptance in invariant energy W (1.6 \u3c = W \u3c = 2.7 GeV) and covered the full range of the kaon production angle at an average momentum transfer Q(2) = 1.90 GeV2. In this experiment a 5.50-GeV electron beam was incident upon an unpolarized liquid-hydrogen target. We have mapped out the W and kaon production angle dependencies of the induced polarization and found striking differences from photoproduction data over most of the kinematic range studied. However, we also found that the induced polarization is essentially Q(2) independent in our kinematic domain, suggesting that somewhere below the Q(2) covered here there must be a strong Q(2) dependence. Along with previously published photo-and electroproduction cross sections and polarization observables, these data are needed for the development of models, such as effective field theories, and as input to coupled-channel analyses that can provide evidence of previously unobserved s-channel resonances

A new method of reconstructing very-high-energy gamma-ray spectra: the Template Background Spectrum

Very-high-energy (VHE, E>0.1 TeV) gamma-ray emission regions with angular extents comparable to the field-of-view of current imaging air-Cherenkov telescopes (IACT) require additional observations of source-free regions to estimate the background contribution to the energy spectrum. This reduces the effective observation time and deteriorates the sensitivity. A new method of reconstructing spectra from IACT data without the need of additional observations of source-free regions is developed. Its application is not restricted to any specific IACT or data format. On the basis of the template background method, which defines the background in air-shower parameter space, a new spectral reconstruction method from IACT data is developed and studied, the Template Background Spectrum (TBS); TBS is tested on published H.E.S.S. data and H.E.S.S. results. Good agreement is found between VHE gamma-ray spectra reported by the H.E.S.S. collaboration and those re-analysed with TBS. This includes analyses of point-like sources, sources in crowded regions, and of very extended sources down to sources with fluxes of a few percent of the Crab Nebula flux and excess-to-background ratios around 0.1. However, the TBS background normalisation introduces new statistical and systematic errors which are accounted for, but may constitute a limiting case for very faint extended sources. The TBS method enables the spectral reconstruction of data when other methods are hampered or even fail. It does not need dedicated observations of VHE gamma-ray-free regions (e.g. as the On/Off background does) and circumvents known geometrical limitations to which other methods (e.g. the reflected-region background) for reconstructing spectral information of VHE gamma-ray emission regions are prone to; TBS would be, in specific cases, the only feasible way to reconstruct energy spectra.Comment: 18 pages, accepted for publication (Astronomy and Astrophysics

Efficacy of Bravecto® Plus spot-on solution for cats (280 mg/ml fluralaner and 14 mg/ml moxidectin) for the prevention of aelurostrongylosis in experimentally infected cats

Background: The feline lungworm Aelurostrongylus abstrusus affects the lower respiratory tract in cats worldwide. As infections may lead to chronic respiratory changes or even death, preventive treatment in cats with outdoor access is warranted. Methods: The preventive efficacy of a spot-on solution (Bravecto® Plus spot-on solution for cats, MSD) against cat aelurostrongylosis was evaluated using three different preventive treatment regimes in a negative controlled, randomized and partially blinded laboratory efficacy study with 31 purposed-bred cats. The minimum recommended dose of 2.0 mg moxidectin + 40 mg fluralaner/kg bodyweight was applied once 12 (Group [G]1), 8 (G2) or 4 (G3) weeks before experimental infection with 300 third-stage larvae (L3) of A.&nbsp;abstrusus. Another group served as untreated control (G4). Individual faecal samples were analysed as of day 30 post infection (pi) to monitor larvae excretion. Necropsy was performed at days 47–50 pi. The lungs were examined macroscopically for pathological findings and (pre-)adult worms were counted to assess preventive efficacy. Results: Beginning at day 32–40 pi, all cats of the control group were constantly shedding larvae of A.&nbsp;abstrusus, whereas only one animal of G1 excreted larvae at several consecutive days. In addition, two cats of G1 and G3 and three of G2 were positive on a single occasion. The geometric mean (GM) of the maximum number of excreted larvae was 7574.29 in the control group compared to 1.10 (G1), 1.19 (G2) and 0.53 (G3), resulting in a GM reduction of &gt; 99.9% in all treatment groups. All lungs of the control animals showed severe or very severe alterations at necropsy, while in 94.44% of the treated cats lung pathology was rated as absent or mild. The GM number of (pre-)adult A.&nbsp;abstrusus retrieved from the lungs was 26.57 in the control group, 0.09 in G1 and 0.00 in G2 and G3. Thus, GM worm count reduction was 99.66% in G1 and 100% in G2 and G3. Conclusions: A single application of Bravecto® Plus spot-on solution at a dose of 2.0 mg moxidectin + 40 mg fluralaner/kg bodyweight reliably prevents cat aelurostrongylosis for at least 12 weeks.[Figure not available: see fulltext.