Accuracy of Swabs, Tissue Specimens, and Lead Samples in Diagnosis of Cardiac Rhythm Management Device Infections

Aims: Pacemaker and implantable-cardioverter defibrillator lead infections widely increased with consequent need to accurately recognize responsible bacteria.
Methods: Between May 2003 and December 2007, we extracted 118 leads, 104 (87.3%) due to infections (sepsis, lead-associated endocarditis, pocket infection) or chronic draining sinus (with negative local bacteriological analyses). Swabs and tissue specimens from pocket and fragments of pin and tip of each extracted lead were obtained during extraction and sent for bacteriological examination.
Results: Cultures from explanted lead pins returned positive results in 100% of the cases presenting with local infections and in 92.5% of those with chronic draining sinus. In cases of sepsis, positive results of blood samples are less common than lead samples (58.3 vs 86.7, P = 0.02), the latter being more sensitive for infection diagnosis. Concordance between bacterial isolates from pocket and lead is quite low, approaching 45%, seemingly due to contamination effect. Concordance between isolates within the lead (pin and tip) is quite high, close to 70%, reflecting a more accurate expression of the real infection. In cases of sepsis, concordance between lead and blood samples, and mainly from tip and blood, is very high, resembling 80–85%; consequently bacterial isolates from the lead, particularly from lead tip, are clearly associated with clinical infections.
Conclusions: Our results strongly support the hypothesis that chronic draining sinus is often sustained by infection. Moreover, diagnostic accuracy of lead samples is higher not only than swabs and tissue samples, but also than blood samples to confirm an infection and to guide effective therapy.     

Doppler echocardiographic assessment of time to peak velocity in the aorta and pulmonary artery of small for gestational age fetuses

Summary. The time to peak velocity was measured at the level of the ascending aorta and pulmonary artery by Doppler echocardiography in 38 small-for-gestational age (SGA) fetuses before and during maternal hyperoxygenation. The values were compared to a reference range derived from the study of 142 appropriate-for-gestational age (AGA) fetuses. In the SGA fetuses the time to peak velocity at the level of pulmonary artery was significantly lower and at the level of the aorta significantly higher than in AGA fetuses. During maternal hyperoxygenation the aortic time to peak velocity decreased towards normal range but there was no significant change at the level of the pulmonary artery. These results may indicate variations of aortic and pulmonary pressures in SGA fetuses that can be partially modified by maternal hyperoxygenation and which may be associated with changes in the peripheral resistance of the cerebral circulation.     

THE FATE OF PATIENTS WITH LOCALLY ADVANCED BLADDER CANCER TREATED CONSERVATIVELY WITH NEOADJUVANT CHEMOTHERAPY, EXTENSIVE TRANSURETHRAL RESECTION AND RADIOTHERAPY: 10-YEAR EXPERIENCE

Purpose

We asses the results of bladder preservation for infiltrating cancer. The potential for neoadjuvant chemotherapy followed by extensive transurethral resection and radiotherapy was evaluated in 40 patients with T2-T4a G2-G3 bladder carcinoma.

Materials and Methods

From 1983 to 1995, 40 patients with bladder cancer underwent bladder sparing treatment, consisting of neoadjuvant chemotherapy, extensive transurethral resection and radiotherapy. Most patients had T3G3 cancer. A deep transurethral resection biopsy was performed before and after chemotherapy, and an extensive transurethral resection was repeated at the end of radiotherapy. Of the patients 30 received cisplatin and methotrexate and 10 also received vinblastine. Total dose of radiotherapy was 60 to 65 Gy. Recurrent superficial tumors were treated transurethrally. Radical cystectomy was considered for persistent or recurrent invasive disease.

Results

Complete response occurred in 19 patients (47.5%) after chemotherapy, and in 8 patients after transurethral resection and radiotherapy (67.5%). Within 10 years 8 responding patients (30%) had local recurrences and 3 underwent cystectomy. Of the patients 14 (35%) are alive, including 13 with no evidence of disease (mean survival 65 months), 5 died of unrelated disease and 21 (52.5%) died of distant metastases (mean survival 28 months). Of the 21 patients 14 had residual tumor after radiotherapy, 3 presented with distant metastases after vesical infiltrating recurrence and 4 had distant metastases in the absence of locoregional recurrence. In 22 patients (55%) the bladder was salvaged. Patients with complete response to chemotherapy had a low risk for recurrent infiltrating tumors and metastases.

Conclusions

Complete tumor control was maintained at 5 years in more than 50% of the patients treated conservatively. Bladder salvage is feasible in select patients.     

Coexpression of CD69 and HLADR activation markers on synovial fluid T lymphocytes of patients affected by rheumatoid arthritis: a three-colour cytometric analysis.

The aim of the present study was to evaluate the coexpression of very early (CD69), early (CD25) and late (HLADR) antigens and to analyse the mean fluorescence intensity (MFI) of such activation markers on synovial fluid (SF) and peripheral blood (PB) lymphocytes of patients affected by rheumatoid arthritis (RA) and other types of chronic synovitis (OCS). A three colour cytometric analysis was performed using a peridinin chlorophyll protein conjugated anti-CD3 antibody in combination with fluorescein isothiocyanate or phycoerythrin labelled anti-CD69, anti-HLADR, anti-CD25 monoclonal antibodies (mAbs). A T cell gating method was utilized, so that three sets of bivariant dot plot quadrant displays were obtained (CD69/HLADR, CD69/CD25, CD25/HLADR). A large percentage of SF T lymphocytes in RA showed the coexpression of very early and late activation antigens (CD3 + CD69 + HLADR +), whereas CD3 + CD69 + CD25 + bearing cells and CD3 + CD25 + HLADR + lymphocytes were only a small percentage. Similar results were obtained in patients with OCS, although to a lesser extent. No statistically significant differences in MFI of CD69 and HLADR positive SF T cells between RA and OCS were observed. The CD69 + CD25-HLADR + T cell subset is the most commonly represented in the synovial environment, among those we have evaluated; this phenotype may be characteristic of chronic inflammatory arthritis.     

INTERLEUKIN 6 GENE-TRANSFECTED MOUSE MAMMARY ADENOCARCINOMA: TUMOUR CELL GROWTH AND METASTATIC POTENTIAL

Cells from the spontaneous metastatic TSA mammary adenocarcinoma of BALB/C mouse were transfected with the murine (interleukin-6) IL6 gene. The clone (TSA-IL6) secreting the largest amount of IL6 displayed an in vitro increased growth rate compared with that of TSA cells transfected with the neomycin resistance gene only (TSA-neo). TSA-IL6 cell colonies consisted mainly of fusiform cells and TSA-neo colonies of polygonal cells. When subcutaneously (s.c.) injected in syngeneic mice, TSA-IL6 cells gave rise to tumours that grew significantly slower than TSA-neo cell tumours. Microscopically, TSA-IL6 tumours displayed a fascicular pattern of growth, associated with a very scanty macrophage infiltrate. S.c. TSA-IL6 tumours were significantly less metastatic than TSA-neo tumours. By contrast, following intravenous (i.v.) challenge, TSA-IL6 cells produced 5–7 times more lung metastases than TSA-neo cells. The i.v. TSA-IL6 cell lung metastases showed a marked macrophage infiltrate and a rich vascularization. The high in vitro TSA-IL6 cell growth rate is attributable to the IL6-induced production of growth factors, some of which possess heparin-binding properties, such as amphiregulin. The differences in vascularization and macrophage infiltrate may underlie the observed differences between s.c. TSA-IL6 tumour growth with low spontaneous metastatic potential and the widespread growth of i.v. metastasis. © 1997 John Wiley & Sons, Ltd.     

Substrate Ablation in Treatment of Atrial Fibrillation

From the time catheter ablation of atrial fibrillation (AF) was first reported, of the two dominant approaches for AF ablation, only pulmonary vein (PV) isolation has been modified, while circumferential pulmonary vein ablation (CPVA) as performed by our group in Milan has remained substantially unmodified. In fact, PV isolation as initially performed by Haissaguerre et al. has undergone rapid evolution toward substrate modification with significantly higher success rates without major complications. Modification of such technique was due to modification of the substrate. It is now evident that substrate modification is indeed crucial for curing AF particularly in patients with long-lasting or permanent AF. Indeed, to achieve good outcomes, any ablation technique should simultaneously include elimination of all triggers associated with modification of both anatomic and autonomic substrate, as we started to do many years ago by performing CPVA.     

Interactions of Monoamine Oxidase Inhibitors,N-Acetylenic Analogues of Tryptamine,with Rat Liver Microsomal Cytochrome P450

Abstract— Interactions between some novel and potent monoamine oxidase inhibitors (MAOIs), acetylenic analogues of tryptamine, and rat liver microsomal cytochrome P450 (P450) as evidenced by visible spectra analysis were analysed. Compounds with a secondary aliphatic amine moiety throughout induced type II difference spectra and exhibited the highest affinity for P450, whereas tertiary amines induced type I spectral changes and showed diminished affinity. P450 dependent aniline hydroxylase activity was inhibited by all compounds in an irreversible time-dependent manner. Only tertiary aliphatic amines constituted the substrate for P450-dependent N-demethylase activity, with comparable kinetic parameters. The N-demethylated metabolites were identified by thin-layer chromatography and mass-spectrometric analyses. These findings describe the role of P450-dependent microsomal mono-oxygenase systems in the metabolism of some MAOI acetylenic tryptamine derivatives and the possible hepatic contribution to adverse interactions between MAOIs, endobiotics and sympathomimetic compounds.     

PROLACTIN STIMULATION BY INTRAVENOUS LABETALOL IS MEDIATED INSIDE THE CENTRAL NERVOUS SYSTEM

We have previously reported that labetalol infusion increases prolactin (PRL) secretion in hypertensive patients. In an attempt to investigate the site where labetalol stimulates PRL, the drug was infused intravenously (100 mg) into healthy subjects, both under basal conditions and after pretreatment with l -dopa plus carbidopa (250 mg and 25 mg respectively every 6 h for 1 day), since this regimen has been reported to blunt the PRL responses to centrally acting stimuli. The effects of oral labetalol administration (100 and 200 mg) on PRL was also evaluated. Serum PRL concentration did not change after oral labetalol, whereas it was increased by intravenous drug administration. This effect was completely abolished by pretreatment with l -dopa plus carbidopa. These findings, though they do not demonstrate the mechanism, suggest that the hyperprolactinaemia induced by labetalol is mediated inside the blood–brain barrier.