Attitude towards genetic testing for breast cancer susceptibility: a comparison of affected and unaffected women

BRUNO M., DIGENNARO M., TOMMASI S., STEA B., DANESE T., SCHITTULLI F. & PARADISO A. (2010) European Journal of Cancer Care 19 , 360–368
Attitude towards genetic testing for breast cancer susceptibility: a comparison of affected and unaffected women The objective of this study is to evaluate women's awareness and interest in genetic testing for breast cancer risk, to identify socio‐demographic factors, to analyse the reasons for wanting or not wanting to be tested and finally to determine whether breast cancer patients and healthy women have different attitudes towards genetic testing. Consecutive series of 879 women without and with breast cancer participated in a 20‐item self‐completing questionnaire. Among breast cancer patients, 57% answered that they would definitely or probably accept being tested, compared with 84% of women without breast cancer. At the multiple logistic regression analysis only to have a diagnosis of breast cancer conditioned significantly the interest to have genetic testing. Surprisingly, a family history of breast cancer was found to have no significant impact. The most frequently cited reason for being interested in genetic testing was ‘to learn about your children's risk’. Although women's awareness about breast cancer genes is inadequate, the interest in genetic testing is substantial and higher both in healthy women and in women with breast cancer. These results provide important indications for the development of educational strategies.     

Determination of the structure of [Nle7]-endothelin by 1H NMR

[Nle⁷]-endothelin was synthesized and studied by ¹H NMR and distance geometry calculations. The NMR study was performed first in DMSO-d₆ and then in 50% acetonitrile/water since this peptide aggregates in pure water. In both cases, all spin systems were identified and assigned with the aid of two-dimensional spectroscopy (2D): COSY (for scalar couplings) and NOESY (for dipolar couplings). On the basis of the acetonitrile/water NMR parameters, and using the DISGEO program, a three-dimensional structure of [Nle⁷]-endothelin is proposed and discussed.     

Long-Term Results After Extracardiac Valved Conduits Implanted for Complex Congenital Heart Disease

Between August 1982 and December 1986, 56 patients survived implantation of an extracardiac valved conduit for complex congenital heart disease. The mean age at operation was 4.2 years (16 days to 24 yrs) and the mean weight was 15.9 kg (2.4 to 93.0 kg). The diagnosis was pulmonary atresia (PA) with ventricular septal defect (VSD) in 13 patients, tetralogy of Fallot in 11, transposition of the great arteries (TGA) with VSD in 8, truncus arteriosus, in 7, complex left ventricular outflow tract obstruction (LVOTO) in 6, complex left atrioventricular valve obstruction in 4, double outlet right ventricle with VSD and subaortic obstruction in 3, univentricular heart with pulmonary stenosis in 2, TGA with LVOTO in 1, and PA with intact ventricular septum in 1. In 35 patients, a preclotted conventional Dacron conduit (CDC) with bioprosthetic valve was used, in 19 patients a collagen-sealed Tascon valved conduit (TC) was implanted, and in 1 patient an aortic homograft was used. In a mean follow-up of 32.5 months (9 to 64 mo), there were two deaths (2/56, 3.6%) that were not related to the conduit. All survivors have been evaluated by two-dimensional and Doppler echocardiography, and 29/56 (51.8%) underwent cardiac catheterization. Nine patients (9/56, 16.1%) underwent successful valved conduit replacement, in seven cases with a nonvalved conduit. There was a significant difference (P = .011) with regard to the incidence of conduit replacement between the group with CDC (2/36, 5.5%) and the group with TC (7/19, 36.8%). Five patients underwent percutaneous transluminal balloon dilatation of the prosthetic conduit, with adequate relief of the gradient in four patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

N200 in the flanker task as a neurobehavioral tool for investigating executive control

Event-related potentials were recorded in a flanker task using arrowheads pointing to the left or to the right as targets and as congruent or incongruent flanker stimuli using squares as neutral flanker stimuli. The onset of the flanker stimuli preceded that of the target stimuli byt 100 ms. Lateralized readiness potentials showed response activation below execution threshold in correspondence to the information conveyed by the flanker stimuli. Exclusively, the incongruent flanker condition provoked a N2c, which evolved closely synchronized to the erroneous response. Graded response analyses separating incongruent trials with weak, medium, and strong incorrect response activation revealed that the N2c amplitude covaried with the magnitude of the erroneous response. The N2c in the incongruent compatibility condition of the flanker task thus corresponds to the avoidance of inappropriate responses, possibly reflecting the inhibition of automatically but erroneously primed responses. The results are compatible with studies of error correction, suggesting that efference monitoring is a constituent of executive control.     

Homing of transplanted bone marrow cells in livers of Schistosoma mansoni‐infected mice

Elkhafif N, Voss B, Hammam O, Yehia H, Mansy S, Akl M, Boehm S, Mahmoud S, El Bendary O, El Fandy G. Homing of transplanted bone marrow cells in livers of Schistosoma mansoni‐infected mice. APMIS 2010; 118: 277–87. The efficiency of differentiation of bone marrow cells (BMCs) into hepatocytes in vivo and its importance in physiopathological processes is still debated. Murine schistosomiasis was used as a liver injury model and unfractionated male mice BMCs were transplanted through intrahepatic injection into non‐irradiated Schistosoma mansoni‐infected female mice on their 16th week post‐infection. Two weeks after bone marrow transplantation, mice were sacrificed on a weekly basis until 10 weeks. Tracing of male donor‐derived cells in female recipient mice livers was carried out by the detection of Y chromosome expression by fluorescent in situ hybridization (FISH) and also of chromodomain Y‐linked (CDYL) protein by indirect immunofluorescence (IF). Their transformation into hepatocytes was studied by double labelling indirect IF using antibodies directed against CDYL and mouse albumin. Histopathological and electron microscopic examinations revealed the presence of small hepatocyte‐like cells in the periportal tracts and in between the hepatocytes facing the sinusoids. Donor‐derived cells showing Y chromosome by FISH and expressing CDYL protein by IF were recovered in the infected transplanted livers. The initial number of these cells increased with increased post‐transplantation time. Cells were mainly localized in the periphery of schistosoma granuloma. Few donor‐derived cells appeared within the hepatic parenchymal tissue and showed positivity for albumin secretion by double labelling with IF. We suggest that transplanted bone marrow stem cells can repopulate the Schistosoma‐infected liver of immunocompetent mice. Their differentiation is a complex event controlled by many factors and needs to be further characterized extensively. The extent and type of liver injury and the number of transplanted cells are important variables in the process of stem cell engraftment and differentiation into functioning hepatic cells that still need to be defined.     

Contextualising psychological distress among regular ecstasy users: The importance of sociodemographic factors and patterns of drug use

Introduction and Aims. Considerable concern has been raised about associations between ecstasy use and mental health. Studies of ecstasy users typically investigate varying levels of lifetime use of ecstasy, and often fail to account for other drug use and sociodemographic characteristics of participants, which may explain mixed findings. The current study aimed to examine the relationship between patterns of recent (last six months) ecstasy use and psychological distress among current, regular ecstasy users, controlling for sociodemographic risk factors and patterns of other drug use. Design and Methods. Data were collected from regular ecstasy users (n = 752) recruited from each capital city in Australia as part of the Ecstasy and related Drugs Reporting System (EDRS). Psychological distress was assessed using the Kessler Psychological Distress Scale (K10). Data were analysed using multinomial logistic regression. Results. Seven per cent of the sample scored in the ‘high’ distress category and 55% in the ‘medium’ distress category. Patterns of ecstasy use were not independently associated with psychological distress. The strongest predictors of distress were female sex, lower education, unemployment, ‘binge’ drug use including ecstasy (use for >48 h without sleep), frequent cannabis use and daily tobacco use. Discussion and Conclusions. Regular ecstasy users have elevated levels of psychological distress compared with the general population; however, ecstasy use per se was not independently related to such distress. Other factors, including sociodemographic characteristics and other drug use patterns, appear to be more important. These findings highlight the importance of targeting patterns of polydrug use in order to reduce drug‐related harm among regular ecstasy users.[George J, Kinner SA, Bruno R, Degenhardt L, Dunn M. Contextualising psychological distress among regular ecstasy users: The importance of sociodemographic factors and patterns of drug use. Drug Alcohol Rev 2010]     

Carcinogenic Evaluation of Estazolam via Diet in CD Strain Sprague-Dawley Rats and B6C3F1 Mice for 2 Years

Carcinogenic Evaluation of Estazolam via Diet in CD Strain Sprague-DawleyRats and B6C3F1 Mice for 2 Years. KIMURA, E. T., FORT, F. L,,BURATTO, B., TEKELI, S., KESTERSON, J. W., HEYMAN, I. A., ANDCUSICK, P. K. (1984). Fundam. Appl. Toxicol. 4, 827–842.A comparative toxicity and carcinogenicity study was carriedout for 2 years with estazolam, a benzodiazepine, via diet inSprague-Dawley rats (0.5, 2, and 10 mg/kg/day) and in B6C3F1mice (0.8, 3, and 10 mg/kg/day). In rats, no biologically significantchanges were seen with respect to mortality, clinical signs,food consumption, or occurrence of palpable masses. Body weightgain in females (10 mg/kg/day) was depressed 12.6% and reflecteda maximum-tolerated dosage (females). Spontaneous and incidentalnonneoplastic lesions were consistent with aging in this speciesand unrelated to drug treatment. No biologically significantdifferences in tumor incidences occurred. Mice were more responsiveto estazolam as suggested by (1) increased mortality (males)at 10 mg/kg/day, (2) increased food consumption and body weightgains (females), (3) withdrawal signs characterized by hyperactivity/aggressivenessand convulsions, and (4) appearance of dose-related nodularhyperplasia of the liver due to the relatively high dosagesused coupled with the propensity of benzodiazepines to enhanceliver enzyme induction. Several spontaneous benign and malignanttumors observed in all groups were not considered to be drugrelated. Based on the findings in these studies, estazolam wasnot considered to be carcinogenic when administered via dietto either rats at 0.5, 2, and 10 mg/kg/day or to mice at 0.8,3, and 10 mg/kg/day for 2 consecutive years.     

Molecular detection of t(8;21)/AML1-ETO in AML M1/M2: correlation with cytogenetics, morphology and immunophenotype

The t(8;21) identifies a subgroup of acute myeloid leukaemia (AML) with a relatively good prognosis which may merit different treatment. It is associated predominantly, but not exclusively, with AML M2, and corresponds to rearrangements involving the AML1 and ETO genes. AML1-ETO positive, t(8;21) negative cases are well recognized but their incidence is unknown. In order to determine optimal prospective AML1-ETO RT-PCR screening strategies, we analysed 64 unselected AML M1 and M2 cases and correlated the results with other biological parameters. Molecular screening increased the overall detection rate from 8% to 14%. AML1-ETO was found in 3% (1/32) of AML M1 and 25% (8/32) of M2, including three patients without a classic t(8;21) but with chromosome 8 abnormalities. It was more common in younger patients. Correlation with morphology enabled development of a scoring system which detected all nine AML1-ETO-positive cases with a false positive rate of 7% (4/55). Although certain AML1-ETO-positive cases demonstrated characteristic immunological features (CD19 and CD34 expression, CD33 negativity), each of these markers was insufficiently specific to permit prediction in an individual case. We conclude that initial routine prospective molecular screening for AML1-ETO in all AMLs, combined with standardized morphological and immunological analysis, is desirable in order to produce improved prognostic stratification and to determine whether screening can ultimately be restricted to appropriate subgroups.     

Successful Catheter Ablation of Atrial Fibrillation

Catheter Ablation of AF. Introduction: Catheter ablation of a case of incessant atrial fibrillation was attempted using linear right atrial lesions created by sequential applications of radiofrequency energy.
Methods and Results: A 46-year-old patient had incessant episodes of atrial fibrillation. He had previously undergone successful radiofrequency catheter ablation of a common atrial flutter. Antiarrhythmic drugs including amiodarone and various drug combinations were ineffective. A 7-French specially designed 14-polar catheter with interelectrode distance of 3 mm was used to create linear lesions in the right atrium. Each electrode was 4 mm in length and able to transmit radiofrequency energy. Three linear lesions, two longitudinal and one transverse that connected the two longitudinal lesions, were created using 30 radiofrequency applications of 10 to 40 W. The final application interrupted an atrial fibrillation that had been persistent for 55 minutes. No sustained atrial fibrillation was inducible despite repeated pacing maneuvers. There was no complication. In short-term follow-up of 3 months, the patient has been free of arrhythmias without antiarrhythmic medication.
Conclusion: Successful catheter ablation of human atrial fibrillation is feasible using linear atrial lesions created by radiofrequency energy delivery. Further studies are mandatory to ascertain the efficacy and safety of this procedure, as well as to assess different catheter techniques.