Implant and long-term evaluation of atrial signal amplification in a single-lead ICD.

BACKGROUND: In patients without clinical indications for pacing the use of a single-lead implantable cardioverter defibrillator (ICD) implementing atrial sensing capability with proper signal amplification management may represent a useful therapeutic option, combining the positive features of both single and dual-chamber devices. The aim of the study was to evaluate the atrial signal amplification and its long-term stability in a single-lead ICD system adding atrial sensing to a standard single-chamber ICD. METHODS: P-wave amplitudes were collected and compared at implant both with a conventional external device ("unfiltered" P wave) and telemetrically with the implanted ICD ("filtered" P wave). Filtered/unfiltered P-wave ratio (amplification factor, AmF) was evaluated at implant and during follow-up. RESULTS: In 43 enrolled patients (38 men, age 64 ± 16 years), the mean filtered P wave at implant was significantly higher than the unfiltered P wave (3.85 ± 0.81 mV vs 2.0 ± 1.49 mV; P < 10(-11) ), with a mean AmF value of 2.77 ± 1.62. In seven patients with atrial fibrillation at implant, the AmF was higher (4.62 ± 1.94) than in patients in sinus rhythm (2.41 ± 1.30; P < 0.001). A significant linear correlation was found between the inverse of P wave and the AmF (R = 0.82, P < 0.00001). In 25 patients followed for 384 ± 244 days, atrial undersensing was never documented and AmF did not change from implant (3.19 ± 1.82; P = 0.24), also in different body position and breathing conditions. CONCLUSIONS: The single-lead ICD system evaluated reliably amplified P-wave amplitudes by a factor of about three, maintaining this performance during the observed follow-up.

Laparoscopic biliopancreatic diversion: our preliminary experience with 201 consecutive cases.

Surgery as a treatment modality for morbid obesity has shown impressive progress over the past decades because of a better understanding of the metabolic characteristics of obesity and the rationale for its surgical treatment. Biliopancreatic diversion was first performed in humans in 1976. Since then it has been an excellent operation for morbid obesity to achieve long-term weight reduction. We present our laparoscopic biliopancreatic diversion protocol, with or without distal gastrectomy (Resa's operation). From 1995 to October 2008 we operated on 201 patients; open biliopancreatic diversion was performed in 48 patients, while the remaining patients underwent laparoscopic biliopancreatic diversion (84 laparoscopic Scopinaro's operations, 69 laparoscopic Resa's operations). The mean operating time was 140 minutes for the open procedures, 180 minutes for Scopinaro's laparoscopic operation and 135 minutes for Resa's laparoscopic operation. The mean postoperative stay was 5.5 days. Our mortality rate consisted of two patients (0.99%) who had pulmonary embolisms. Other major complications were three cases of leakage from the jejuno-ileal anastomosis, 18 cases of incisional hernia, 6 cases of metabolic diseases; 1 case of acute hepatitis and 1 case of bronchopneumonia. Biliopancreatic diversion can be performed satisfactorily by laparoscopy. A factor that may reduce the technical difficulties and make the technique totally reversible is the gastric sparing. Thus an upper digestive endoscopy can determine preoperatively whether the patient will need a gastrectomy, depending on its results.

Hsp70 is required for optimal cell proliferation in mouse A6 mesoangioblast stem cells.

Mouse Hsp70 (70 kDa heat shock protein) is preferentially induced by heat or stress stimuli. We previously found that Hsp70 is constitutively expressed in A6 mouse mesoangioblast stem cells, but its possible role in these cells and the control of its basal transcription remained unexplored. Here we report that in the absence of stress, Ku factor is able to bind the HSE (heat shock element) consensus sequence in vitro, and in vivo it is bound to the proximal hsp70 promoter. In addition, we show that constitutive hsp70 transcription depends on the co-operative interaction of different factors such as Sp1 (specificity protein 1) and GAGA-binding protein with Ku factor, which binds the HSE consensus sequence. We used mRNA interference assays to select knockdown cell clones. These cells were able to respond to heat stress by producing a large amount of Hsp70, and produced the same amount of Hsp70 as that synthesized by stressed A6 cells. However, severe Hsp70 knockdown cells had a longer duplication time, suggesting that constitutive Hsp70 expression has an effect on the rate of proliferation.

Performance of a ventricular automatic-capture algorithm in a wide clinical setting.

BACKGROUND: The optimal programming of a pacemaker (PM) voltage output considers both efficiency (prolonging battery cell longevity) and patient safety (adequate safety margin). Currently, automatic capture (AC) algorithms are designed to ensure safe automatic stimulation threshold determination and pacing with a safety margin. METHODS: The aims of this prospective observational study were (1) to evaluate, over a short-term follow-up, the extent of backup pacing in patients implanted with an AC-featured PM produced by Boston Scientific (Insignia) and a wide range of ventricular leads; (2) to identify patient- or lead-specific predictors of ventricular threshold increase or missed detection of the ventricular pacing threshold; and (3) to analyze day-to-day fluctuations in the ventricular pacing threshold and the relationship between their magnitude, the characteristics of patients, and the system implanted. RESULTS: Five hundred and seventy-nine patients implanted with 89 different leads were followed up for a median of 2.1 months. Five hundred and thirty-six patients (92.5%) never experienced failure of automatic threshold testing; 571 (98.6%) did not experience permanent failure requiring continuous backup pacing at high energy. On multivariate analysis, none of the patient or lead characteristics predicted the occurrence of high-energy backup pacing during the study period. Day-to-day threshold fluctuations were associated only with higher thresholds (>1 V). CONCLUSION: AC algorithm reliably measures ventricular pacing thresholds in most patients: in only 1.4% of patients the system is permanently unable to detect the ventricular threshold. Backup pacing is not dependent on lead or patient characteristics, including lead polarization, polarity, and maturation.

Hsp70 localizes differently from chaperone Hsc70 in mouse mesoangioblasts under physiological growth conditions.

Mouse A6 mesoangioblasts express Hsp70 even in the absence of cellular stress. Its expression and its intracellular localization were investigated under normal growth conditions and under hyperthermic stress. Immunofluorescence assays indicated that without any stress a fraction of Hsp70 co-localized with actin microfilaments, in the cell cortex and in the contractile ring of dividing cells, while the Hsc70 chaperone did not. Hsp70 immunoprecipitation assays confirmed that a portion of Hsp70 binds actin. Immunoblot assays showed that both proteins were present in the nucleus. After heat treatment Hsp70 and actin continued to co-localize in the leading edge of A6 cells but not on microfilaments. Although Hsp70 and Hsc70 are both basally synthesized they showed different cellular distribution, suggesting an Hsp70 different activity respect to the Hsc70 chaperone. Moreover, we found Hsp70 in the culture medium as it has been described in other cell types.

Role of rate control and regularization through pacing in patients with chronic atrial fibrillation and preserved ventricular function: the VRR study.

AIM: High heart rates in chronic atrial fibrillation (CAF) is one of the factors responsible for hemodynamic alterations and may lead to tachycardiomyopathies. The ventricular rate regulation (VRR) study evaluates the effect of ventricular rate regularization in CAF patients with preserved ventricular function, marked ventricular rate variability, and indications for pacemaker (PM) implantation owing to symptomatic pauses. Rate regularization was achieved using VRR algorithm (INSIGNIA pacemakers, Guidant Corp., St. Paul, MN, USA). METHODS: One month after PM implantation, 58 patients followed two 3-month crossover periods (VRR-OFF; VRR-ON) in which the VRR algorithm was randomized and compared to fixed rate stimulation at 60 ppm. During follow-up visits a 6-minute walk test was performed under partially inhibited conditions (PM at 40 ppm) and ventricular response was recorded. The following parameters were measured: mean ventricular rate (MR), rate variability (RR30), rate recovery after exercise (SLOPE = (R-END - R-REC)/(R-END - 40)), R-END being the rate at end of walk and R-REC the rate 1 minute after exercise. RESULTS: The VRR algorithm decreased rate variability (RR30: -7.36 +/- 8.8; P < 0.01) without increasing ventricular rate (MR: -1.11 +/- 8.3 P = NS), while SLOPE improved significantly (SLOPE: +15.41 +/- 16.8 P < 0.01). CONCLUSIONS: VRR effectively stabilizes rate, without increasing pacing rate above spontaneous rhythm and helps achieve a more favorable autonomic balance, improving rate recovery after exercise.

Atrial tachyarrhythmia burden modelling by some electrophysiological parameters in pacemaker-recipient patients with Brady-Tachy syndrome.

AIMS: (1) To correlate atrial tachyarrhythmia (AT) burden of pacemaker-recipient Brady-Tachy syndrome (BTS) patients with a number of diagnostics-derived parameters after 1 month of DDD pacing; (2) to asses whether the activation of atrial overdrive or conventional rate-responsive pacing may affect relevant variables and their correlation. METHODS AND RESULTS: After 1 month of DDD pacing, rate-responsive function or persistent atrial overdrive was randomly activated for 3 months, in 92 BTS patients. Some pacemaker diagnostics parameters collected at 1- and 4-month follow-ups were included in multiple linear regression models, whose dependent variable was the Log transformation of AT burden and compared. With 1-month data, the only variables significantly correlating with Log AT burden were average (with a regression coefficient estimate of -0.07, P=0.02) and standard deviation (0.10, P=0.007) of atrial rate, mean premature atrial contraction (PAC) coupling interval (CI) (-0.005, P=0.001), frequency of PACs with CI<500 ms (1.30, P<10(-6)). Atrial pacing percentage (APP) and ventricular pacing percentage (VPP), PACs with CI>500 ms did not significantly correlate. Four-month data largely confirmed these results, except that in DDDR atrial rate average and standard deviation no longer correlated. Overdrive significantly increased APP and reduced PACs with CI>500 ms. CONCLUSION: AT burden showed significant dependence in DDD and during overdrive on atrial rate average and standard deviation. Highly premature PACs always significantly correlated with AT burden. Though increasing APP, which unexpectedly never correlated, overdrive could only reduce less premature PACs.

Mechanisms of Ca2+ liberation at fertilization.

The mechanisms underlying the Ca2+ release at fertilization of several animal organisms are reported. Four main classical theories are described, i.e., that of Ca2+ release following simple sperm contact and a G protein stimulation; that of simple sperm contact followed by a tyrosine kinase receptor activation; that of the necessity of introduction by sperm into the egg of molecules for Ca2+ release; and that the molecule introduced into the marine eggs for Ca2+ release is the same Ca2+. Two other mechanisms for Ca2+ release are also illustrated: that of ryanodine receptor stimulation and that of NAADP formation.

Nickel, lead, and cadmium induce differential cellular responses in sea urchin embryos by activating the synthesis of different HSP70s.

Treatment with heavy metals, such as nickel, lead or cadmium, elicits different cellular stress responses according to the metal used and the length of treatment. In Paracentrotus lividus embryos the inducible forms of HSP70 (HSP70/72) are different in molecular mass from the constitutively expressed HSP75, and they can be used as markers of cellular stress. Even a short treatment with each metal induces the synthesis of HSP70/72 which remain stable for at least 20h and differ little in their isoelectric points. Continuous treatment from fertilization with nickel or lead produces late irregular pluteus embryos, with peak HSP70/72 synthesis at blastula followed by the arrest of synthesis by pluteus. On the contrary, the same treatment with cadmium induces continuous HSP70/72 synthesis and produces irregular gastrula embryos which then degenerate. Moreover, a long treatment induces over control embryos a slight increase in the amount of constitutive HSP75 during development while lead treatment depresses constitutive HSP75 at early stages and doubles its quantity at late stages.

Localization of HSP70, Cdc2, and cyclin B in sea urchin oocytes in non-stressed conditions.

In Paracentrotus lividus embryos, a Mediterranean sea urchin species, HSP70 is present in all the cells. During cell division it localizes under normal growth conditions on the centrosomes and on the whole isolated mitotic apparatus. Now, in situ hybridization, Western blot analyses, and immunohistochemistry show that the HSP70 mRNA is present in both small and large P. lividus oocytes, that all four isoforms of HSP70 can be found also in the oocytes, and that a certain amount of HSP70 localizes on asters and spindles during polar body formation. Moreover, two representative cell-cycle related proteins, cyclin B, and Cdc2, are present both in small and large oocytes, concentrating in the germinal vesicles before its breaking down. Cdc2 has been found in the cytoplasm of small oocytes and in the germinal vesicles of the large ones and then together with HSP70 on the mitotic apparatus of the dividing oocytes.

Developmental biology for undergraduate students at the University of Palermo, Italy.

This article describes a course for undergraduate students required for graduation in the Biological Sciences given by one of us (G. Giudice). The second author (K. Onorato) is responsible for computer graphics. Included in the description is a review of the various topics which are discussed in the lectures, as well as a collection of the graphics which accompany many of the lecture topics. Axis formation is reviewed in various model systems, and organogenesis, as it is understood at the molecular level in several genetic systems, is presented. Sex determination is reviewed in Drosophila and Caenorhabditis, followed by a discussion of developmental phenomena which involve clear-cut cellular interactions. Finally, assorted topics such as urodele limb regeneration, cell division control, aging and left-right asymmetry determination are presented.

[Isolated non-compaction of left ventricle in childhood: clinical experience with 5 cases]. / Non compattazione isolata del ventricolo sinistro in età pediatrica: esperienza clinica su cinque casi.

BACKGROUND: Isolated noncompaction of the left ventricular myocardium, a rare congenital disorder, is thought to be due to an arrest of myocardial morphogenesis. It is characterized by an excessively prominent trabecular meshwork and by deep intertrabecular recesses. The aim of this study was to clarify the late outcome of this malformation, reporting our experience on 5 pediatric patients observed for a period of 11 years. METHODS: We describe the clinical, electrocardiographic and echocardiographic findings of 5 pediatric cases, with an age ranging from 1 month to 10 years. The mean follow-up was 4.5 years (> 10 years in 1 patient). RESULTS: In no case did life-threatening ventricular arrhythmias or systemic embolic events occur. Four patients who developed heart failure have been submitted to digoxin, diuretic, angiotensin-converting enzyme and anticoagulant therapy. One of them is still asymptomatic and in good health. One patient died while on the waiting list for cardiac transplantation. CONCLUSIONS: The appropriate and early diagnosis and treatment of this disorder can improve the outcome even though further studies will be needed to elucidate its long-term prognosis. At the same time, in view of the high incidence of a positive family history, evaluation of all members of the family is warranted.

Apical ventricular septal defect with reverse bidirectional transseptal flow: a sign of restriction within the right ventricle.

Apical ventricular septal defects (VSD) may spontaneously become restricted or may even close following tissue outgrowth within the right ventricle in the region of the apical muscle bundles. We report a case of spontaneous restriction of an apical VSD localized within the right ventricle in the region of prominent apical trabeculae, in which pulsed Doppler interrogation showed an unusual pattern of bidirectional blood flow across the VSD, with right to left flow in systole and left to right in diastole. Angiography confirmed these unusual aspects. This reverse bidirectional transseptal flow is due to the physiological incorporation of the apical part of the right ventricular cavity in the left ventricle and may be, in the absence of right outflow obstruction, a sign of restriction of the VSD inside the right ventricle.

Genes of the sea urchin embryo: An annotated list as of December 1994.

The main literature regarding gene structure and expression in sea urchin embryos is schematically reported and briefly commented upon. Although the subject has expanded particularly over the last 10 years, to which the review mostly refers, some historical reference is also given. More space is reserved to the regulation of the synthesis of histones and cytoskeletal actins, where the attention of various authors has been especially present; the regulation of such a synthesis is described both at a territorial level and a temporal level during the sea urchin development.

A study on the effect of the inhibition of polyadenylylation on the production of giant cytoplasmic RNA in sea urchin embryos.

It is suggested that inhibition of RNA polyadenylylation in sea urchin mesenchyme blastulae causes a disturbance of the transport of all the size classes of newly synthesized RNA from the nucleus to the cytoplasm.

Synthesis of RNA in isolated nuclei of sea urchin embryos.

It is demonstrated that isolated nuclei of sea urchin embryos are able to incorporate radioactive nucleotides into RNA.Some properties of the incorporation system are described.

Effect of chemical animalization and vegetalization on the synthesis of ribosomal RNA in sea urchin embryos.

Treatment of embryos of Paracentrotus lividus with a concentration of ZnSO4 which causes animalization, strongly inhibits the initiation of ribosomal RNA synthesis.The vegetalizing agent LiCl does not seem clearly to affect the synthesis of this RNA.

Gene expression in sea urchin development.

Actinomycin D has been administered for various lengths of time and at various concentrations to developing sea urchin embryos. The results obtained support the following suggestions. (1) The shape of respiratory curve up to the mesenchyme blastula stage is not under direct gene control. (2) The RNA needed for gastrulation seems to be made during the period between early and late blastula. (3) The RNA needed for skeleton differentiation is continously made from some time before early gastrula throughout skeleton growth. (4) The process of development of skeleton is extremely sensitive to actinomycin.