Venous thromboembolism is a relevant and underestimated adverse event in cancer patients treated in phase I studies.

BACKGROUND: To investigate, retrospectively, the role of tumour histotype and antiangiogenic drugs for venous thromboembolism (VTE) development in advanced cancer patients treated in phase I studies. METHODS: Patients enrolled and treated in phase I studies conducted by SENDO (Southern Europe New Drugs Organisation) were considered. RESULTS: Data of 1415 patients were included in the analysis: 526 (37.2%) patients were males, median age was 57.3 years (range: 13-85). Fifty-six (3.96%) patients developed a VTE. At multivariate analysis gynaecologic (hazard ratio (HR): 2.8, 95% confidence interval (CI): 1.29-6.23, P=0.009) and gastrointestinal tumours (HR: 3.23, 95% CI: 1.18-8.87, P=0.023) as well as combination regimens of cytotoxic and antiangiogenic agents (HR: 2.6, 95% CI: 1.11-6.30, P=0.028), white blood cell >11,000 µl(-1) (HR: 2.59, 95% CI: 1.10-6.09, P=0.028) and haemoglobin<10 g dl(-1) (HR: 3.1, 95% CI: 1.07-8.94, P=0.037) were statistically correlated with VTE development. Venous thromboembolism was the fourth most common cause of drug discontinuation. The median time from first drug administration to discontinuation was 1.4 for VTE and 2.3 months for the other adverse events (P=0.02). CONCLUSION: Venous thromboembolism is a relatively common complication among patients treated in the context of phase I studies, and may lead to early drug discontinuation. A greater risk of developing VTE is associated with the diagnosis of gynaecologic and gastrointestinal tumours and the combined use of chemotherapy and antiangiogenic drugs.

Incidence, risk factors and clinical implications of venous thromboembolism in cancer patients treated within the context of phase I studies: the 'SENDO experience'.

BACKGROUND: To investigate the incidence, risk factors and clinical implications of venous thromboembolism (VTE) in advanced cancer patients treated in phase I studies. PATIENTS AND METHODS: Patients enrolled and treated in phase I studies conducted by SENDO (Southern Europe New Drugs Organization) Foundation between 2000 and 2010 in 15 experimental centers were considered for the study. Clinical data, including adverse events, were prospectively collected during the studies and retrospectively pooled for VTE analysis. RESULTS: Data of 1415 patients were considered for analysis. Five hundred and twenty-six (37.2%) patients were males, and median age was 57.3 years (range: 13-85). Eighty-five percent of patients had metastatic disease, while the remaining had locally advanced irresectable disease. For 706 (49.9%) of the patients, the study treatment was with cytotoxic agent(s) only, for 314 with target therapy(ies) only, while the remaining patients received a target therapy in combination with a cytotoxic drug. Fifty-six (3.96%) patients who developed a VTE, almost all (89.3%) during the course of treatment, the remaining during the follow-up. At univariate analysis, the Khorana score, the combination of an antiangiogenic agent with a cytotoxic drug, and the time from first cancer diagnosis to study entry (as continuous variable) were associated with a statistically significant increase of VTE occurrence. The multivariate analysis confirmed only a statistically significant association for the Khorana score. The hazard ratio of VTE occurrence was 7.88 [95% confidence interval (CI) 2.86-21.70) and 2.74 (95% CI 1.27-5.92) times higher for the highest (≥3) and intermediate (1-2) scores as compared with score = 0. CONCLUSIONS: VTE is a relatively common complication among patients treated in the context of phase I studies. The Khorana score predicts VTE development and can be used to identify patients at high of VTE.

Prevention of diabetes-increased aging effect on rat collagen-linked fluorescence by aminoguanidine and rutin.

Products from the advanced Maillard reaction, which increase during aging and diabetes, may contribute to the development of the typical pathology of aging and diabetes. These compounds are detectable only by their characteristic fluorescence, and few data based on long-term studies are available. For this reason, we studied subcutaneous skin collagen fluorescence in 57 nondiabetic (10- to 110-wk-old) and 74 streptozocin-induced diabetic (10- to 22-wk-old) rats. An exponential increase (r = 0.969, P less than 0.001) of collagen-linked fluorescence (excitation at 370 nm, emission at 440 nm) was observed with aging; after a lag, diabetes induced an earlier dramatic elevation of the fluorescence, suggesting a more complicated phenomenon than simple accumulation. To prevent such increases, the effects of 1 g.kg-1.day-1 aminoguanidine, suggested to be an inhibitor of the advanced glycosylation reaction, and 1 g.kg-1.day-1 rutin, an aldose reductase inhibitor, in drinking water were tested. Both treatments had a significant lowering effect on collagen fluorescence in diabetic rats. The mechanisms by which aminoguanidine and rutin prevent the accumulation of fluorescence are unknown, but these observations raise the question of whether they could be identical. If fluorescence is a marker for age-related pathologies and diabetic sequelae, aminoguanidine and rutin could have therapeutic effects in their prevention.

Differential effect of 9 beta-chloro-16, 16-dimethyl prostaglandin E2 (nocloprost) on the radiation response of human normal fibroblasts and colon adenocarcinoma cells.

The possible influence of 9 beta-chloro-16,16-dimethyl prostaglandin E2 (nocloprost) on the effect of 137Cs gamma irradiation was investigated comparatively in human normal fibroblasts and colon adenocarcinoma cells. By itself, the compound did not influence the proliferation of cells of either cell type or the clonogenic capacity of carcinoma cells. Moreover, nocloprost did not induce any DNA strand breakage, as evaluated by neutral elution, in cells of either cell type. A 2-h incubation with nocloprost before irradiation induced an enhancement of fibroblast survival after an exposure of 10 Gy. This protective effect was not observed in adenocarcinoma cells under the same treatment conditions. The amount of double-strand breaks induced by 50 Gy was reduced in normal cells but not in tumor cells exposed to the prostaglandin analog before irradiation. Moreover, incubation with nocloprost for 2 h after irradiation remarkably enhanced the rate of rejoining of DNA breaks in fibroblasts but not in adenocarcinoma cells. Overall, these findings indicate a specific radioprotective effect of nocloprost in normal cells and no influence of the compound on the cytotoxic effect of ionizing radiation on colon adenocarcinoma cells.

[Depression and nutrition in a group of women during climacteric]. / Depressione e alimentazione in un gruppo di donne in climaterio.

Depression and eating disorders are often combined. Depression and weight changes are often observed in climacteric women. In our study the possibility of an association of depressive reactions and eating behavioral changes are assessed among 42 climacteric patients.

Attachment and detachment processes as a typological index of relational systems.

Attachment and detachment processes, as defined by modern attachment theories, place them as integrative between innate and acquired behaviors, like a regulatory system for every close relationship. As a consequence, family attachment styles, which proceed-throughout development-together with personal identity construction processes, stress the notion of relationship as a dialectical and interactive process, defining the irreducible duality of human experience, in which the personal individuality construction is linked, since the earliest phases of life, to the significant relationships. Dysfunctional patterns of attachment and detachment and self-construction processes interact in defining personal organizations one can observe in psychopathological situations; some clinical examples are proposed.

In vivo studied on the metabolism of dibenzo [c,f]-[1,2] diazepine.

The in vivo metabolism of dibenzo [c,f]-[1,2] diazepine (I) was studied after i.p. administration to rats, in order to observe the influence of the heteroatom on the metabolic pathway. Metabolites were separated by chromatography and their structures elucidated by mass spectrometry, by both gas chromatography coupled with mass spectrometry and the direct inlet system. Six metabolites were identified, some of them by direct comparison with authentic samples.

In vitro studies on the metabolism of dibenzo[c,f]-[1,2]diazepine.

Dibenzo [c,f]-[1,2] diazepine is a new compound with a tricyclic structure and a double bond between two nitrogen atoms in positions 1 and 2 of the molecule. Its in vitro metabolism has been studied, incubating the compound with rat liver microsomes. Two metabolites have been identified: dibenzo [c,f] - [1,2]diazepine-1-N-oxide and a monohydroxyderivative in the aromatic ring.

Nutritional epidemiology during school age.

Nutritional research covers different fields, two of which are of particular interest: evaluation of the nutritional status, and epidemiology of food consumption. For many years, studies in these fields have been promoted by our research group, which bases its methodology on anthropometric measurements, bioelectrical impedance measurements, and check of nutritional habits. Our studies involve more than 2500 subjects from pre-school age to adolescence. This work represents the basis for an educational approach with the ultimate aim of improving life styles. One of our first studies on school meals during nursery period and composition and application of "dietary tables" showed inadequacies of energy intakes and macronutrients distribution. In another study, aimed to evaluate the intake of soluble sugars, more than 2/3 of participating school children were found to consume more than 70 g of soluble sugars per day, while 10% of them exceeded 150 g/day. Results of the following study, in which special attention was given to salted and sweet snacks, showed that snacks can account for 34% of the total daily energy intake; although its adequacy, the energy distribution per macronutrients showed a clear imbalance. As for adolescence, a very critical age, the evaluation of weight self-perception revealed that only 62% of them had a correct perception of their weight. This research also devoted special attention to home prepared breakfast, which is consumed by the vast majority of enrolled subjects, although only rarely it is nutritionally adequate. A double age-related trend could thus be drawn: on one side, there is the tendency of the "overweight status" to decrease (from a starting-point of about 20%); on the other side, this tendency is unfortunately compensated by the increasing trend of "obesity" (which almost reaches 30%).

Follow-up of mediastinal lymphoma: role of ultrasonography.

PURPOSE: Patients with lymphoma are often young and require long and intensive treatment, the toxic effects of which compound the impact of frequent radiological examinations. Computed tomography (CT) is of great value in the evaluation of the mediastinum, which is frequently involved by the disease, but carries a high radiation load. Ultrasonography (US) has therefore been proposed as an alternative procedure to evaluate response to treatment. Major advantages include good compliance, absence of patient risks, low cost, easy reproducibility, dynamic images enabling multiplanar evaluation and qualitative and quantitative criteria. The purpose of this study was to investigate the role of US in evaluating response to treatment in patients with mediastinal lymphomas using CT as the gold standard. MATERIALS AND METHODS: In 2005, 12 patients were evaluated by chest X-ray, mediastinal sonography and contrast-enhanced CT (gold standard). Each mediastinal region was accurately assessed for adenopathies. Lymph nodes were studied by evaluating their structure and morphology, measuring their size and classifying them according to location. RESULTS: US proved to be more sensitive and accurate (93%) than X-ray [66% sensitivity and 68% diagnostic accuracy (DA)]. In particular, the best sensitivity values were observed in the supraaortic (97% vs. 55%), prevascular (97% vs. 39%) and paratracheal (87% vs. 77%) regions and in the aortopulmonary window (80% vs. 0%). Deeper mediastinal compartments (subcarinal region and posterior mediastinum) could not be assessed. X-ray proved to be superior in hilar adenopathies only. US provides qualitative information (hypoechoic or hyperechoic tissues) in addition to quantitative data (maximum diameter of each lymph node) it shares with CT. DISCUSSION.: Compared with X-ray, US allows for a better evaluation of the anterior mediastinal regions, showing small, central adenopathies that do not alter the mediastinal lines on X-ray. It is, however, of very limited value in the evaluation of posterior compartments because of their deep location. US adds qualitative criteria to the quantitative criteria typical of CT. Limitations of mediastinal US include site of adenopathies, dependence on the patient's characteristics (body habit, concurrent diseases and chest anatomy) and dependence on the operator. CONCLUSIONS: US may have a specific role in monitoring patients with mediastinal adenopathies, providing early indications on possible response to treatment and allowing the frequency of CT follow-up scans to be reduced. In conclusion, US may be used to complement, but not replace CT, which remains the gold standard.