Der Beweis für die Kontraktilität der Lungengefäße und die Beziehung zwischen Lungendurchblutung und O2-Resorption

Naunyn-Schmiedeberg's Archives of Pharmacology - Mittelst einer neuen Methode kann die pharmakologische Beeinflussung der Lungenzirkulation bestimmt werden. Es wird einerseits der Druck in der...     

Zur Kenntnis der Lungenvasomotoren

Zusammenfassung Durch Unterbindung eines Bronchus und Einschieben des so isolierten Lungenteiles in einen Plethysmographen erhält man rein zirkulatorisch bedingte Volumschwankungen (E. Weber). — Diese Methode erweist sich als ungeeignet zum Studium der pharmakologischen Beeinflussung der Lungengefäße, während bei unserer Versuchsanordnung die physiologischen Verhältnisse völlig gewahrt bleiben.Offenbar werden durch die Bronchusunterbindung noch näher zu untersuchende Bedingungen geschaffen, welche dienormalen Reaktionen auf pharmakologische Eingriffe abändern, teilweise direkt umkehren; dadurch werden irrige Schlußfolgerungen veranlaßt.Mit 2 Kurven.     

Improving Wait Times and Patient Experience Through Implementation of a Provincial Expedited Diagnostic Pathway for BI-RADS 5 Breast Lesions

Annals of Surgical Oncology - Long diagnostic intervals following abnormal breast imaging (DI) cause patient anxiety and possibly poorer prognosis. This study evaluates the effect of a provincial...     

Combined inhibition of EGFR and CK2 augments the attenuation of PI3K-Akt-mTOR signaling and the killing of cancer cells

Ser/Thr protein kinase CK2 regulates multiple processes that play important roles in the sensitivity of cancer to epidermal growth factor receptor targeting therapeutics, including PI3K-Akt-mTOR signaling, Hsp90 activity, and inhibition of apoptosis. We hypothesized that top-down inhibition of EGFR, combined with lateral suppression of multiple oncogenic pathways by targeting CK2, would create a pharmacologic synthetic lethal event and result in an improved cancer therapy compared to EGFR inhibition alone. This hypothesis was tested by combining CX-4945, a first-in-class clinical stage inhibitor of CK2, with the EGFR tyrosine kinase inhibitor, erlotinib, in vitro and in vivo in models of non-small cell lung carcinoma, NCI-H2170, and squamous cell carcinoma, A431. Our results demonstrate that combination of CX-4945 with erlotinib results in enhanced attenuation of the PI3K-Akt-mTOR pathway. We also observed an increase in apoptosis, synergistic killing of cancer cells in vitro, as well as improved antitumor efficacy in vivo. Taken together, these data position CK2 as a valid pharmacologic target for drug combinations and support further evaluation of CX-4945 in combination with EGFR targeting agents.     

NSD1 analysis for Sotos syndrome: insights and perspectives from the clinical laboratory.

PURPOSE: Sotos syndrome is a genetic disorder characterized primarily by overgrowth, developmental delay, and a characteristic facial gestalt. Defects in the NSD1 gene are present in approximately 80% of patients with Sotos syndrome. The goal of this study was to determine the incidence of NSD1 abnormalities in patients referred to a clinical laboratory for testing and to identify clinical criteria that distinguish between patients with and without NSD1 abnormalities. METHODS: Deletion or mutation analysis of the NSD1 gene was performed on 435 patients referred to our clinical genetics laboratory. Detailed clinical information was obtained on 86 patients with and without NSD1 abnormalities, and a clinical checklist was developed to help distinguish between these two groups of patients. RESULTS: Abnormalities of the NSD1 gene were identified in 55 patients, including 9 deletions and 46 mutations. Thus, in the clinical laboratory setting, deletions were found in 2% and mutations in 21% of samples analyzed, because not all patients had both tests. Thirty-three previously unreported mutations in the NSD1 gene were identified. Clinical features typically associated with Sotos syndrome were not found to be significantly different between individuals with and without NSD1 abnormalities. The clinical checklist developed included poor feeding, increased body mass index, and enlarged cerebral ventricles, in addition to the typical clinical features of Sotos syndrome, and was able to distinguish between the two groups with 80% sensitivity and 70% specificity. CONCLUSIONS: The dramatic decrease in the frequency of finding NSD1 abnormalities in the clinical laboratory is likely because of the heterogeneity of the patient population. Our experience from a diagnostic laboratory can help guide clinicians in deciding for whom NSD1 genetic analysis is indicated.     

PCR detection of granulocytic ehrlichiae in Ixodes ricinus ticks and wild small mammals in western Switzerland

The presence of granulocytic ehrlichiae was demonstrated by PCR in Ixodes ricinus ticks and wild small mammals in Switzerland in two areas of endemicity for bovine ehrlichiosis. Six ticks (three females and three nymphs) (1.4%) of 417 I. ricinus ticks collected by flagging vegetation contained ehrlichial DNA. A total of 201 small mammals from five species, wood mouse (Apodemus sylvaticus), yellow-necked mouse (Apodemus flavicollis), earth vole (Pitymys subterraneus), bank vole (Clethrionomys glareolus), and common shrew (Sorex araneus), were trapped. The analysis of I. ricinus ticks [corrected] collected on 116 small mammals showed that nine C. glareolus voles and two A. sylvaticus mice hosted infected tick larvae. In these rodents, granulocytic ehrlichia infection was also detected in blood, spleen, liver, and ear samples. Further examinations of 190 small mammals without ticks or with noninfected ticks showed the presence of ehrlichial DNA in spleen and other tissues from six additional C. glareolus, three A. flavicollis, and one S. araneus mammals. This study suggests that A. sylvaticus, A. flavicollis, S. araneus, and particularly C. glareolus are likely to be natural reservoirs for granulocytic ehrlichiae. Partial 16S rRNA gene sequences of granulocytic ehrlichiae from ticks and rodents showed a high degree of homology (99 to 100%) with granulocytic ehrlichiae isolated from humans. In contrast, groESL heat shock operon sequence analysis showed a strong divergence (approximately 5%) between the sequences in samples derived from rodents and those derived from samples from questing ticks or from other published ehrlichia sequences. Dual infections with granulocytic ehrlichia and Borrelia burgdorferi were found in ticks and small mammals.