Use of DDDRP pacing device in prevention and treatment of tachy-brady syndrome after Mustard procedure

A 13-year-old male patient, who underwent Mustard operation for a very complex congenital heart disease (CHD), after palliation presented a decrease of the sinus node function, developing a tachy-brady syndrome and a mild dysfunction of atrioventricular (AV) conduction. He was successfully treated using a DDDRP pacemaker, which ensured a suitable atrial rhythm and was able to interrupt supraventricular tachycardia episodes. Until now, hospitalization related to episodes of heart failure or symptomatic arrhythmia, has not been necessary.     

1-Thioangelicin: crystal structure, computer-aided studies and photobiological activity

1-Thioangelicin is a furocoumarin analog synthesized to investigate the role of the substitution of sulfur for oxygen in the parent compound angelicin. The compound was examined by X-ray diffraction, and its interaction with DNA, both in the dark and by UVA irradiation, studied by means of linear flow dichroism, chromatography and (1)H NMR. Further insight into the steric and electronic features of 1-thioangelicin has been reached through theoretical calculations, including molecular mechanics optimization, docking studies and frontier molecular orbital investigations. The experimental data indicate that thioangelicin is able to intercalate in the DNA helix and subsequent irradiation yields a cis-syn adduct, in agreement with theoretical calculations within the lower/higher singly occupied molecular orbital formalism. Antiproliferative activity has been assessed on Balb/c 3T3 cultured cells.     

Breast irradiation with three conformal photon fields for patients with high lung involvement

Since 2001, 50 breast cancer patients, for whom extensive lung/heart involvement was expected from the use of conventional tangential 2-field technique (2F) owing to complex anatomies, were irradiated using a 3-field conformal technique (3F). Dose plans were designed for both 3F and 2F and a dose volume histogram analysis on ipsilateral lung, heart, and target was conducted. The 3F technique allowed a significant reduction in ipsilateral lung irradiation: mean dose dropped from 16.0±3.8 (2F) to 12.0±2.7 Gy (3F) and V_45Gy from 20.7±6.8 (2F) to 3.2±2.9% (3F). Similarly, in patients irradiated to the left breast, heart mean dose was reduced from 8.1 Gy (2F) to 6.8 Gy (3F) and D_15% from 19.0 Gy to 14.0 Gy. All differences reached a high degree of significance. The target coverage was not clinically compromised since the slight reduction using 3F compared with 2F is limited to V_95% while V_90% difference, even if statistically significant, is small: 98.2±1.8% (3F) and 98.8±1.6 (2F). A preliminary report on clinical follow up is also included; with a mean follow up of 15.8 months, no pulmonary or cardiac complications were observed.     

Diagnostic applications of cardiac multislice CT with sixteen-row scanner: state of the art

Coronary angiography is nowadays the diagnostic standard in the evaluation of coronary artery anatomy, in the identification of stenoses and in the follow-up of revascularization procedures (PTCA-stenting, bypass). The limitations of such technique in terms of invasivity and high cost has targeted research efforts towards the development of non invasive diagnostic tools. Technological evolution in the field of helical CT has provided 2, 4, 8 and 16 detector-row multislice scanners characterized by progressive improvements in terms of spatial and temporal resolution that have made them increasingly suitable for the analysis of moving structures with high quality anatomic detail. The main cardiologic applications of multislice CT include coronary calcium scoring, the evaluation of coronary vascular anatomy and disease, follow-up of revascularization procedures (stenting, bypass), and the evaluation of cardiac walls and chambers. The aim of this paper is to describe the applications of sixteen detector-row multisclice CT in non invasive evaluation of cardiac and coronary diseases.     

Arrhythmogenic right ventricular cardiomyopathy type 1 (ARVD1): confirmation of locus assignment and mutation screening of four candidate genes

Arrhythmogenic right ventricular cardiomyopathy type 1 (ARVD1) is an autosomal dominant disorder characterised by progressive degeneration of right ventricular myocardium, arrhythmias and risk of sudden death. By linkage analysis, we previously mapped the involved gene to chromosome 14q24.3. In the present study we report on linkage analysis of one additional and unrelated family, which enabled to confirm previous locus assignment. Another family is reported, in which genetic and clinical data suggest linkage to the same locus. Direct sequencing of DNA from individuals belonging to established ARVD1 families failed to detect causative mutations in exonic sequences of four genes (POMT2, TGFbeta3, KIAAA1036 and KIAA0759) expressed in the heart and which defects could possibly induce plasma membrane instability or apoptosis, key features of ARVD pathogenesis.     

Medicinal chemistry of A2A adenosine receptor antagonists

Due to the clearly demonstrated receptor-receptor interaction between adenosine A(2A) and dopamine D(2) receptors in the basal ganglia, the discovery and development of potent and selective A(2A)adenosine receptor antagonists became, in the last ten years, an attractive field of research to discovery new drugs for the treatment of neurodegenerative disorders, such as Parkinsons disease. Different compounds have been deeply investigated as A(2A) adenosine receptor antagonists, which could be classified in two great families: xanthine derivatives and nitrogen poliheterocyclic systems. These studies led to the discovery of some highly potent and selective A(2A) adenosine receptor antagonists such as ZM241385, SCH58261 and some xanthine derivatives (KW6002), which have been used as pharmacological tools for studying this receptor subtype. However, those compounds showed some problems that do not permit their use in clinical studies, such as poor water solubility (SCH58261, and xanthine derivatives) or good affinity for A(2B) adenosine receptor subtype (ZM241385). In the last few years great efforts have been made to overcome these problems, trying to optimize not only the pharmacological profile but also the pharmacokinetic character of this class of compounds. The aim of this report is to briefly summarize the recent progress made in this attractive field of research.     

Pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine derivatives as adenosine receptor antagonists. Influence of the N5 substituent on the affinity at the human A 3 and A 2B adenosine receptor subtypes: a molecular modeling investigation

A new series of pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines bearing various substituents at both the N5-pyrimidinyl and N8-pyrazolyl positions have been synthesized, and their binding affinities at the four human adenosine receptor subtypes (hA(1), hA(2A), hA(2B), and hA(3)) have been evaluated. All the described compounds contain arylacetyl moieties at the N5 position and arylalkyl substituents at the N8 position. Surprisingly, all the compounds present their most potent affinities at the hA(2B) adenosine receptor with a range of selectivities against the other subtypes. When bulky groups are present simultaneously at the N5 and N8 positions (e.g., compound 9), the best selectivity for the hA(2B) receptor was observed (K(i)(hA(1)) = 1100 nM; K(i)(hA(2A)) = 800 nM; K(i)(hA(2B)) = 20 nM; K(i)(hA(3)) = 300 nM, K(i)(hA(1)/A(2B)) = 55, K(i)(hA(2A)/A(2B)) = 40, K(i)(hA(3)/hA(2B)) = 15). To understand the molecular significance of these results, we compared the putative TM (transmembrane) binding motif of compound 9 on both hA(2B) and hA(3) receptors. From our docking studies, compound 9 fits neatly inside the TM region of the hA(2B) receptor but not in the corresponding hA(3) region, illustrating significant differences between the two subtypes. The study herein presented permits an understanding of why the bioisosteric replacement of an -NH, present in previously reported hA(3) receptor antagonists, with a -CH(2) group at the N5 position induces such large differences in hA(2B)/hA(3) affinity. In the molecular structure of the hA(3) receptor, two residues, Ser243 (TM6) and Ser271 (TM7), create a hydrophilic region, which seems to permit a better accommodation of the phenylurea series into this putative hA(3) binding site than the phenylacetyl series.     

Cxcl10 enhances blood cells migration in the sub-ventricular zone of mice affected by experimental autoimmune encephalomyelitis

The peri-ventricular area of the forebrain constitutes a preferential site of inflammation in multiple sclerosis, and the sub-ventricular zone (SvZ) is functionally altered in its animal model experimental autoimmune encephalomyelitis (EAE). The reasons for this preferential localization are still poorly understood. We show here that, in EAE mice, blood-derived macrophages, T and B cells and microglia (Mg) from the surrounding parenchyma preferentially accumulate within the SvZ, deranging its cytoarchitecture. We found that the chemokine Cxcl10 is constitutively expressed by a subset of cells within the SvZ, constituting a primary chemo-attractant signal for activated T cells. During EAE, T cells and macrophages infiltrating the SvZ in turn secrete pro-inflammatory cytokines such as TNFα and IFNγ capable to induce Mg cells accumulation and SvZ derangement. Accordingly, lentiviral-mediated over-expression of IFNγ or TNFα in the healthy SvZ mimics Mg/microglia recruitment occurring during EAE, while Cxcl10 over-expression in the SvZ is able to increase the frequency of peri-ventricular inflammatory lesions only in EAE mice. Finally, we show, by RT-PCR and in situ hybridization, that Cxcl10 is expressed also in the healthy human SvZ, suggesting a possible molecular parallelism between multiple sclerosis and EAE.     

Peri-operative outcomes of patients with stage IV endometriosis undergoing robotic-assisted laparoscopic surgery

We analyzed peri-operative outcomes of 80 patients who underwent robotic-assisted laparoscopic surgery and were diagnosed with stage IV endometriosis (revised American Society for Reproductive Medicine) between January 2007 and December 2010 at a tertiary gynecologic oncology referral center with a fellowship training program. Eligible women had a combination of one or more factors: pelvic mass, sub-acute or chronic pelvic pain, dysmenorrhea, dyspareunia, elevated serum CA-125, diagnosed with stage IV endometriosis at surgery with robotic-assisted gynecologic procedures using the da Vinci^? Surgical System. The mean age was 43.7?±?7.0?years, body mass index 27.5?±?7.4?kg/m², and 23 (28.9%) patients had prior endometriosis surgery. Presenting symptoms included: chronic pelvic pain (48.8%), dysmenorrhea (40.3%), and dyspareunia (33.8%). Sixty-nine (86%) patients had pelvic masses (43 unilateral and 26 bilateral). Thirty-seven (46.3%) had elevated CA-125 levels (mean 97.9?±?71.6 U/ml). Forty-eight (60%) underwent robotic-assisted laparoscopic hysterectomy (RALH)/bilateral salpingo-oophorectomy (BSO), 9 (11.3%) RALH/unilateral salpingo-oophorectomy (USO), 5 (6.3%) modified radical hysterectomy, and 10 (13%) USO or BSO only. Four (5%) had ovarian cystectomies with excision of endometriotic implants. Three (3.8%) underwent appendectomy and no patient required bowel resection. Four (5%) patients required conversion to laparotomy during the first 15 cases of this series [dense adhesions (3) and ureteral injury (1)]. Mean operative time was 115?±?46?min, blood loss 88?±?67?ml, and length of stay 1.0?±?0.4?days. There were four (5%) complications (ureteral injury, cuff abscess, cuff hematoma, re-admission for nausea and vomiting secondary to narcotics) and no transfusions. One (1.3%) patient underwent a second surgery for pain (dyspareunia). Robotic-assisted surgery for stage IV endometriosis resulted in excellent pain relief, with few laparotomy conversions or complications during a robotic learning-curve experience.