Experience of donation and quality of life in living kidney and liver donors.

Italian guidelines on living donation demand that we ascertain the donor's free and informed consent. Assessments to do so have to be conducted by an independent 'third party' who has nothing to do with the medical team treating the recipient. From February 2002 to December 2006, the Veneto Regional Authority's Third Party Commission evaluated 201 living liver and kidney donors. A sample of these were contacted after their surgery to assess their living donation experience and quality of life (QoL); 81 were eligible for the assessment and 69 (85.2%) responded. All donors involved in the study completed an anonymous document that included the SF-36 and a questionnaire on their donation experience. The majority (96%) of the sample expressed a positive global opinion of the experience. We concluded that the donation had positive effects on their QoL and that family support had a fundamental influence on their general well-being, and their psychic balance in particular. Some crucial issues emerged, however, i.e. 11% of donors judged the information received before the operation inadequate, 17% reported a subjective perception of bodily changes after the operation and 14% were concerned about their current health: these findings emphasize the importance of informing potential donors thoroughly before they submit to surgery.     

The development of fatal myocarditis and polymyositis in mice heterozygous for IFN-gamma and lacking the SOCS-1 gene

Mice lacking the gene encoding the suppressor of cytokine signaling-1 (SOCS-1 -/-) and heterozygous for the IFN-gamma gene (IFN-gamma +/-) avoided the IFN-gamma-dependent preweaning death of SOCS-1 -/- IFN-gamma +/+ mice but did not exhibit the good health of young adult SOCS-1 -/- IFN-gamma -/- mice. SOCS-1 -/- IFN-gamma +/- mice died within 160 days of birth with massive T lymphocyte, macrophage, and eosinophil infiltration of all skeletal muscles and a similar severe myocarditis. The cornea also developed inflammatory infiltration and often a corneal ulcer. The mice exhibited evidence of selective CD8 T lymphocyte activation in populations in the thymus, spleen, and lymph nodes and focal T- and B-lymphoid infiltrates developed in the lung and salivary gland without apparent tissue damage. Comparison of SOCS-1 -/- IFN-gamma +/- mice with various control mice indicated that the development of tissue-damaging T lymphocyte, macrophage, and eosinophil infiltrates required loss of SOCS-1 and the presence of some IFN-gamma, but that the lung lymphoid infiltrates required only loss of SOCS-1 to develop.     

Efficacy and safety of dabigatran in patients with atrial fibrillation scheduled for transoesophageal echocardiogram-guided direct electrical current cardioversion: a prospective propensity score-matched cohort study

Patients with atrial fibrillation (AF) are predisposed to a hypercoagulable state and are at an increased risk for thromboembolic events when undergoing procedures. This study investigated the long-term efficacy and safety of newly initiated anticoagulation with dabigatran versus uninterrupted vitamin K antagonist (VKA) therapy in patients with AF scheduled for transesophageal echocardiogram (TEE)-guided direct electrical current cardioversion (DCC). Consecutive adult patients with persistent AF scheduled to undergo DCC were included in the study. Patients received dabigatran 110 mg or 150 mg twice daily (bid) or VKA at therapeutic doses for at least 3?weeks before and 4?weeks after DCC. All patients underwent anamnestic, clinical, electrocardiographic and echocardiographic evaluation at each follow-up visit, and were followed up for a total period of 2 years. The primary efficacy outcome was the composite of stroke/transient ischaemic attack and systemic embolism. The primary safety outcome was major bleeding. 176 patients receiving dabigatran (77% dabigatran 150 mg bid) were propensity score-matched to 176 patients on VKA therapy. A low incidence of atrial thrombus (0.6%) at TEE was found in both groups (0.6%). The acute cardioversion success rate was 85.1% in the dabigatran group (149/175) and 83.4% in the VKA group (146/175). During the follow-up period, a similar low incidence of thromboembolic events (0.6%) was reported in both groups; the bleeding safety profile tended to favour dabigatran over VKA (1.1% vs 1.7%; P?=?0.3). Newly initiated anticoagulation with dabigatran in patients with nonvalvular AF scheduled for TEE-guided DCC seems to be as effective and safe as uninterrupted VKA therapy, during long-term follow up.     

Aromatase overexpression enhances the stimulatory effects of adrenal androgens on MCF7 breast cancer cells

The intratumoral conversion of adrenal androgens into estrogens by the aromatase enzyme complex may be an important mechanism of autocrine stimulation in hormone-dependent breast tumor. The effects of estrogens on tumor development are mediated by the activity of estrogen receptor alpha that induces gene expression and cell proliferation. Thus, estrogen biosynthesis 'in situ' and/or estrogen receptor action are the main targets of endocrine treatment in endocrine-dependent breast carcinoma. In the present study we demonstrate that three major adrenal androgens, dehydroepiandrosterone, 5-androstene-3beta, 17beta-diol and 4-androstene 3,17-dione, all acquire an estradiol-like biological efficacy in aromatase transfected MCF7 breast cancer cells. Our results suggest that in postmenopausal women aromatase inhibitors might be considered as an adjuvant approach to the treatment of hormone-dependent breast tumors that overexpress aromatase.     

Elastography: new developments in ultrasound for predicting malignancy in thyroid nodules

BACKGROUND: Elastography is a newly developed dynamic technique that uses ultrasound (US) to provide an estimation of tissue stiffness by measuring the degree of distortion under the application of an external force. US elastography has been applied to differentiate malignant from benign lesions. PATIENTS: This study included 92 consecutive patients with a single thyroid nodule who underwent surgery for compressive symptoms or suspicion of malignancy on fine needle aspiration cytology. Tissue stiffness on US elastography was scored from one (greatest elastic strain) to five (no strain). RESULTS: On US elastography: scores 1 and 2 were found in 49 cases, all benign lesions; score 3 in 13 cases, one carcinoma and 12 benign lesions; and scores 4 and 5 in 30 cases, all carcinomas. Thus, the elasticity scores 4-5 were highly predictive of malignancy (P < 0.0001), with a sensitivity of 97%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 98%. In 32 patients with an indeterminate fine needle aspiration result, the conventional US was not predictive of malignancy, while an US elastographic score of 4-5 was observed in six of seven (86%) patients with carcinoma on histology, and a score of 1-3 in all 25 patients with benign lesions. CONCLUSIONS: US elastography has great potential as an adjunctive tool for the diagnosis of thyroid cancer, especially in indeterminate nodules on cytology. Larger prospective studies are needed to confirm these results and establish the diagnostic accuracy of this new technique.     

Murine hematopoietic blast colony-forming cells and their progeny have distinctive membrane marker profiles

Two distinct bone marrow-derived blast colony-forming cells can generate colonies of lineage-restricted progenitor cells in agar cultures of murine bone marrow. Both cell types selectively had a Kit⁺ ScaI⁺ phenotype distinguishing them from most lineage-restricted progenitor cells. Multicentric blast colony-forming cells stimulated by stem cell factor plus interleukin-6 (IL-6) (BL-CFC-S) were separable from most dispersed blast colony-forming cells stimulated by Flt3 ligand and IL-6 (BL-CFC-F) using CD34 and Flt3R probes. Multicentric BL-CFC-S cofractionated with colony-forming units, spleen (CFU-S) supporting the possibility that the 2 cells may be identical. The colony populations generated by BL-CFC-S were similar in their phenotype and proliferative capacity to progenitor cells in whole bone marrow but the progeny of BL-CFC-F were skewed with an abnormally high proportion of Kit⁻ Flt3R⁺ cells whose clonogenic cells tended to generate only macrophage progeny. Both blast colony populations had a high percentage of GR1⁺ and Mac1⁺ cells but BL-CFC-F colonies also contained a significant population of B220⁺ and IL-7R⁺ cells relevant to the superior ability of BL-CFC-F colony cells to generate B lymphocytes and the known dependency of this process on Flt3 ligand and IL-7. The commitment events and phenotypic changes during the generation of differing progenitor cells in blast colonies can now be clonally analyzed in a convenient in vitro culture system.     

Serial assessment of human tumor burdens in mice by the analysis of circulating DNA

Internal human xenografts provide valuable animal models to study the microenvironments and metastatic processes occurring in human cancers. However, the use of such models is hampered by the logistical difficulties of reproducibly and simply assessing tumor burden. We developed a high-sensitivity assay for quantifying human DNA in small volumes of mouse plasma, enabling in-life monitoring of systemic tumor burden. Growth kinetics analyses of various xenograft models showed the utility of circulating human DNA as a biomarker. We found that human DNA concentration reproducibly increased with disease progression and decreased after successful therapeutic intervention. A marked, transient spike in circulating human tumor DNA occurred immediately after cytotoxic therapy or surgery. This simple assay may find broad utility in target validation studies and preclinical drug development programs.     

Detection of aromatase and estrogen receptors (ERalpha, ERbeta1, ERbeta2) in human Leydig cell tumor

A Leydig cell tumor is a rare neoplasm, deriving from the interstitial cells, whose pathogenesis has not been still defined. Leydig cells of normal adult testis are known as physiological targets for estrogens. However, some studies on transgenic rodents suggest a role of estrogens in the development of Leydig cell hyperplasia and Leydig cell tumor. Therefore, with the aim to evaluate a possible link between estrogens and testicular tumorigenesis, this study investigated the expression of aromatase and estrogen receptors (ERalpha, ERbeta(1), ERbeta(2)) in testes from two patients with Leydig cell tumor. A strong immunoreactivity for aromatase, ERbeta(1), and ERbeta(2), together with a detectable ERalpha immunostaining, was revealed in tumoral tissues. These findings were confirmed by western blot analysis of tumor extracts detecting a 55 kDa P450arom, a 67 kDa ERalpha band, a 59 kDa ERbeta(1) band, and a 53 kDa ERbeta(2) band. The pattern of ER expression in neoplastic cells appears different from that of control Leydig cells exhibiting only ERbeta(1) and ERbeta(2) isoforms. The authors hypothesize how the high estrogen production could play a role in the neoplastic transformation of Leydig cells, while the exclusive presence of ERalpha in tumoral cells could amplify estradiol-17beta signaling contributing to the tumor cell growth and progression.     

Combined clinical, thyroid ultrasound and cytological features help to predict thyroid malignancy in follicular and Hupsilonrthle cell thyroid lesions: results from a series of 505 consecutive patients

OBJECTIVE: The cytological patterns of follicular and Hupsilonrthle cell nodules are included among the indeterminate results of fine-needle aspiration cytology, because distinction between benign and malignant lesion can only be made on histological criteria. The diagnostic value of atypia at cytology, clinical parameters and echographic patterns were examined to establish the risk of malignancy in 505 patients with follicular and Hupsilonrthle cell thyroid nodules at cytology. DESIGN AND PATIENTS: The study included 505 consecutive patients who had undergone thyroidectomy from the period 2002-2005. RESULTS: Histological diagnosis of malignancy was carried out in 125 of 505 (25%) patients, the follicular variant of papillary carcinoma being the most frequent histotype. Only atypia at cytology (P < 0.0001) and spot microcalcifications at ultrasound (P = 0.009) were predictive of malignancy. Male gender, normal thyroid volume, single nodularity, nodule hypoechogenicity, size and blurred margins were associated with malignancy, although not significantly. An arbitrary clinical score allowed the identification of patients with high (41%, 110 patients) and low (16%, 242 patients) risk of malignancy. Combining the clinical score with the presence of atypia at cytology we could identify 30 patients (6%) in whom the risk of malignancy was as high as 63%. CONCLUSIONS: Twenty-five per cent of patients with a cytological result of follicular and Hupsilonrthle cell thyroid lesion had a final diagnosis of malignancy. Only atypia at cytology and spot microcalcifications at thyroid ultrasound were significantly associated with malignancy. Other clinical parameters and thyroid ultrasound patterns can be used to set up a clinical score useful for predicting the individual risk of malignancy before surgery.