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.     

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.     

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.     

Phase I study of gemcitabine and liposomal doxorubicin in relapsed ovarian cancer

Twenty-three patients were enrolled in a phase I study conducted to determine the maximum tolerated doses (MTD) of combined liposomal doxorubicin (CAE) and gemcitabine (GEM) in relapsed ovarian cancer patients. A total of 82 courses are evaluable, with a median number of three cycles administered per patient (range 2-8). GEM was administered on days 1 and 8 by 30-min intravenous infusion immediately after CAE given by 60-min intravenous infusion on day 1; cycles were repeated every 21 days. The starting doses were CAE 20 mg/m(2) and GEM 600 mg/m(2). Following dose levels were 20/800; 20/1,000; 30/800; 30/1,000; 35/800, and 35/1,000 for CAE and GEM, respectively. The MTD was reached at dose level 5, with febrile neutropenia and thrombocytopenia as dose-limiting toxicities. After the MTD, granulocyte-colony stimulating factor was administered in 15% of cycles. Non-hematological toxicity was mild and manageable. All patients are so far evaluable for response. Among them, 5 partial responses (21.7%; 95% confidence interval, CI: 4.9-38.5), 5 disease stabilizations (21.7%, 95% CI: 4.9-38.5) and 13 progressions (56.6%, 95% CI: 36.4-76.8) have been registered. These results warrant further research in a phase II study.     

Cardiovascular risk in hypertensive patients: results of the Pandora project

BACKGROUND: The aim of the Pandora project is to collect epidemiological information, check diagnostic and therapeutic pathways, and assess outcomes in a large hypertensive population. This report presents the results on patients enrolled in the study between 1997-1999. METHODS: Twenty-one general practitioners working in the Ravenna Local Health Service took part in the study. They were supplied with IBM compatible PCs and were trained to enter the patient's data (age, gender, familiarity for cardiovascular diseases, smoking, hospitalisations for cardiovascular disorders, diabetes, blood pressure, total cholesterolemia, creatininemia, antihypertensive therapy) on So.Ge.Pa. software. Cardiovascular risk factors were assessed according to the WHO - ISH joint committee recommendations. RESULTS: 2,608 treated hypertensive patients were enrolled, 65% of whom showed inadequate blood pressure control. The prevalence of inadequate BP control was higher in patients on multiple-drug antihypertensive therapy compared with those on monotherapy (71.9% vs. 47.9%), in older than in younger patients (70.7% vs. 56.1%) and in patients with three cardiovascular risk factors, or diabetes, or affected target organs, compared to those with two or less risk factors (72.4% vs. 63.3%), (p < 0.001 for all). 63.6% of patients were at risk for age, 36.6% for family history of cardiovascular diseases and 31.7% for severe hypercholesterolemia. CONCLUSIONS: BP control was inadequate in a large percentage of patients, but it was particularly unsatisfactory in the elderly and in patients with high cardiovascular risk. A cluster of cardiovascular risk factors was found in both adequately and inadequately controlled hypertensive patients.     

Urban air pollution and respiratory emergency visits at pediatric unit, Reggio Emilia, Italy

Short-term effects of air pollution on daily mortality and hospital admissions for respiratory causes are well documented. Few studies, however, explore the association between exposure to air pollution and daily emergency room visits for respiratory disorders, particularly in Italy and particularly among children as a susceptible population. A time-series analysis was conducted to explore the short-term association between air pollutants (PM10, total suspended particulates [TSP], NO2, SO2, CO, O3) and pediatric emergency room (ER) visits in a small city of northern Italy, Reggio Emilia, during the period 03/01/2001-03/31/2002. There were 1051 ER visits included in the study. Data were analyzed using generalized additive models (GAM), adjusting for various confounding variables, including temperature, humidity, and pollens (Graminaceae). The analyses were also stratified according to the nationality of children (Italians and foreigners). In single-pollutant models, the strongest associations were observed at lag 3 for a 10-microg/m3 increase of TSP (2.7% increase in ER, 95% CI 0.7-4.6) and PM10 (3.0% increase, 95% CI 0.4-5.7), and at lag 4 for a 10-microg/m3 increase of NO2 (11.0% increase in ER, 95% CI 3.6-18.8). At lag 3, the percentage increase in ER visits is similar for the 2 groups of children (Italians and foreigners) for TSP and PM10. The results of the study support the findings that air pollution is a relevant determinant of deterioration of respiratory health among children.     

A novel PTPN11 gene mutation bridges Noonan syndrome, multiple lentigines/LEOPARD syndrome and Noonan-like/multiple giant cell lesion syndrome

Noonan (NS) and multiple lentigines/LEOPARD syndromes (LS) have proved to be associated with distinct PTPN11 mutations. Noonan-like/multiple giant cell lesion syndrome (NLS) is a rare disease, characterised by short stature, facial dysmorphisms, congenital heart defect (CHD) and central giant cell lesions. PTPN11 gene mutations have been reported in a single NLS family and two sporadic patients. Here we report a patient with a complex phenotype progressing throughout the years from NS at birth towards LS and NLS. PTPN11 gene analysis disclosed a novel missense mutation (Ala461Thr) in exon 12, affecting the consensus sequence of the SHP2-active site. This observation joins together NS and LS to NLS into a unique genetic defect, broadening the clinical and molecular spectrum of PTPN11-related disorders.     

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.