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Aims: The aim of the study was to describe the microbiological findings of cardiac implantable electronic devices (CIEDs) infection in the 2000-2011 period at the Cardiology Unit of New Santa Chiara Hospital in Pisa (Italy)., Methods and Results: Removed CIED leads and pocket material were seeded on solid media and isolates tested for antimicrobial susceptibility with the Kirby Bauer method. Electrodes from 1204 patients were analysed and 854 (70.9%) tested positive. In 663 (77.6%) cases only one species was isolated, in 175 (20.5%) two species, and in 14 (1.8%) >2 species. In 116 cases material from the pocket was also cultured. The result was consistent with that from the electrodes in 69 (59%) cases. In 359 cases a blood sample was also obtained for culture. The result was consistent with that from the leads in 124 (35%) cases. A total of 1068 strains were isolated from electrodes. Gram-positive organisms were most frequently isolated (92.5% of isolates); particularly, coagulase-negative staphylococci (CoNS), mainly Staphylococcus epidermidis, in 69% of cases and Staphylococcus aureus in 13.8%, Gram-negative rods in 6.1%, yeasts in 1% and molds in 0.4%. Overall, Oxacillin resistance was 30%, in particular 33% among CoNS and 13% among S. aureus. Oxacillin resistance and quinolones resistance have increased in the period 2006-2011 with respect to the 5 years before. Seventeen percent of Enterobacteriaceae strains had a phenotype compatible with extended spectrum beta-lactamase expression., Conclusions: Culture of the leads offers the possibility of an aetiological diagnosis in the majority of cases. When material from the pocket can be obtained, the microbiological result is often consistent with that from the electrodes, while species isolated from blood cultures are often different and more likely to be the result of contamination. Cardiac implantable electronic device infection is more often monomicrobial, CoNS are most frequently isolated and S. epidermidis is largely the main single agent. Very early infections were associated with S. aureus infection. The pattern of susceptibility to antimicrobials is in general that of community-acquired infections, although oxacillin resistance and quinolones resistance has increased in the last 5 years.

Posttranslational processing of the TSH receptor (TSHR) involves proteolysis of a single chain holoreceptor into TSHR-alpha (or A) and TSHR-beta (or B) subunits, which remain associated via disulfide bonds and which may then form oligomers. As both uncleaved and cleavage-derived forms of this receptor have been reported to bind TSH and transduce signals, reasons for this cleavage into alpha- and beta-subunits have remained enigmatic. Recently we suggested that TSHR cleavage was related to receptor oligomerization and now we have asked if cleavage influenced the binding of G proteins to this receptor. Furthermore, as TSHR-alpha subunits are subject to shedding from the cell surface membrane, we have examined whether the remaining TSHR-beta subunits could mediate signaling themselves, either constitutively and /or ligand-induced. We found that only the cleaved form of the TSHR in transfected Chinese hamster ovary cells was able to bind Gsalpha protein, suggesting that cleavage of the native TSH receptor was associated with receptor activation. We also found that independently expressed TSHR-beta subunits on stable cell lines were unable to mediate either constitutive or TSH-induced signaling, as monitored by their inability to induce cAMP accumulation. These data suggested that receptor cleavage was intimately associated with receptor activation in the wild-type TSH receptor and that the residual TSHR-beta subunits left on the thyroid cell membrane, after TSHR cleavage and subsequent TSHR-alpha shedding, were essentially silent and did not participate in signal transduction.

Hyperfunctioning thyroid adenomas are clonal neoplasms with the intrinsic capacity of growing and differentiate independently of thyroid-stimulating hormone (TSH). We analysed the mRNA encoding thyrotropin receptor of 11 adenomas obtained by fine needle aspiration biopsy (FNAB) and found 7 mutants all located in three aminoacids clustered in the sixth transmembrane domain of the receptor. These mutations were somatic and specifically present in the tumour tissue. DNA sequence revealed that 80 to 90% of the mutations can be rapidly screened and identified by restriction enzyme analysis of the amplified cDNA obtained from the FNABs. The mutation Thr->Ile was introduced in the wild type receptor and expressed in mouse fibroblasts. These cells constitutively activate the transcription of a reporter gene under the control of cyclic AMP responsive element.