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.

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.

Ultrasound diagnosis of pneumothorax.

PURPOSE: The purpose of this study was to show the effectiveness of ultrasound (US) in the evaluation of pneumothorax by comparison with X-rays and computed tomography (CT). MATERIALS AND METHODS: A series of 184 patients (130 men and 54 women), aged 26 to 82 years, underwent chest US after percutaneous needle biopsy. US findings were compared with CT postbiopsy selective slices and to X-rays. RESULTS: Pneumothorax was identified in 46 patients (25%) by CT, in 44 by US, with no false positives, and in 19 by X-rays. US sensitivity was 95.65%, specificity 100% and diagnostic effectiveness 98.91%. CONCLUSIONS: Chest US was found to be a valuable diagnostic tool in pneumothorax diagnosis, with diagnostic effectiveness well beyond X-rays and similar to CT.

Contrast-enhanced ultrasonography in Crohn's disease.

PURPOSE: The purpose of this study was to demonstrate the diagnostic efficacy of contrast-enhanced power Doppler (CEPD) after ultrasound (US) with colour power Doppler (CPD) in defining disease activity in patients with ileal Crohn's disease in the acute phase and during treatment follow-up. MATERIALS AND METHODS: The study included 15 patients with ileal Crohn's disease, 12 of whom were examined in the acute phase of their illness and then 30-60 days after treatment. Three patients were studied during clinical quiescence. All patients were examined prior to treatment with US-CPD study and then with contrast-enhanced power Doppler (CEPD) examination (CEPD) with the use of US contrast agent (SonoVue, Bracco), together with clinical assessment and laboratory tests. Disease activity was defined by the Crohn's Disease Activity Index (CDAI) and some of the most sensitive biohumoural markers. After initial US, CPD and CEPD were performed to assess enhancement of the thickened bowel wall with the use of a reference box and a semiquantitative scoring system. RESULTS: The CEPD study is more reliable then US-CPD in the diagnosis of Crohn's disease and statistically agrees significantly with clinical and laboratory indices for disease activity. CONCLUSIONS: This study demonstrates the importance of US-CPD in the follow-up of patients with Crohn's disease and suggests systematic use of the US contrast agent, which can improve diagnostic performance of abdominal US study. It also provides more information about patients both in the acute phase and during follow-up, thus improving treatment planning and better monitoring of treatment efficacy.

Familial occurrence of migraine with aura in a population-based study.

OBJECTIVE: To better define a possible genetic basis for migraine with aura (MWA). METHODS: We investigated the familial occurrence of migraine with aura in a sample of (MWA) subjects recruited from an epidemiologic study of migraine with aura involving the general population. The sample with migraine with aura (n = 26) was selected out of a total of 1392 subjects (842 women and 550 men) representative of the general population aged 18 to 65 years in the southern Italian town of San Severo. A family history of migraine with aura was determined via direct interviews with all living first-degree relatives of the 26 subjects who could be reached by investigators, 119 people: 71 women and 48 men. The diagnosis of migraine with aura was made according to the 1988 International Headache Society (IHS) criteria. RESULTS: Of the 26 subjects with migraine with aura, 7 (6 women and 1 man) had a positive family history, with a total of 7 first-degree relatives affected by the disease (1 mother, 2 fathers, 1 brother, 1 sister, and 2 children). Based on the lifetime prevalence rate of migraine with aura (1.6%) in the San Severo general population, the relative risk of migraine with aura in the first-degree relatives of the subjects was 3.68 (4.16 for women and 2.77 for men). CONCLUSION: Our subjects' relative risk rate for familial occurrence of migraine with aura was similar to that reported by one investigator, but markedly lower than that reported by another group.

Estrategias de codificación de la memoria visual en la enfermedad de Alzheimer y en el deterioro de memoria asociado a la edad / Visual memory encoding strategies in Alzheimers disease and in age-related memory impairment

Objetivo: 1. Determinar las diferencias en las estrategias de codificación en la memoria visual entre un grupo control de sujetos normales, y pacientes con Enfermedad de Alzheimer (EA) y con Deterioro de Memoria Asociada a la Edad (DMAE). 2. Definir las estrategias de codificación autogestadas aún presentes. Metodología: Comparemos 14 pacientes con EA (criterios del NINCDS-ADRDA 3-4); 14 pacientes con DMAE (criterios de Crook, GDS 2) y 16 sujetos control respecto a las estrategias de codificación de la memoria visual usando la Figura Compleja de Rey (FCR). Las diferencias intergrupales fueron estudiadas con el test de Kruskall Wallis y las correlaciones con coeficiente de Spearman. Resultados: Observamos diferencias intergrupales en el recuerdo inmediato de la FCR (KW = 7,49; p < 0,002) y en el recuerdo diferido (KW = 5,96; p < 0,05). La producción en la copia y en la evocación inmediata de la FCR presentó correlaciones negativas con el nivel de deterioro cognitivo (r = -0,70 p < 0,001). Los controles y los pacientes con DMAE mostraron alta frecuencia de uso de la estrategia sintética en el recuerdo diferido de la FCR mientras que los EA usaron mayormente estrategia no sintéticas o caóticas (x² Fisher = 3,50 p < 0,03). Conclusiones: Los resultados sugieren la mantención de las estrategias de codificación autogestadas presentes puede tener una influencia positiva sobre la memoria en el DMAE, pero es poco probable en la EA. (AU)

Estrategias de codificación de la memoria visual en la enfermedad de Alzheimer y en el deterioro de memoria asociado a la edad / Visual memory encoding strategies in Alzheimer's disease and in age-related memory impairment

Objetivo: 1. Determinar las diferencias en las estrategias de codificación en la memoria visual entre un grupo control de sujetos normales, y pacientes con Enfermedad de Alzheimer (EA) y con Deterioro de Memoria Asociada a la Edad (DMAE). 2. Definir las estrategias de codificación autogestadas aún presentes. Metodología: Comparemos 14 pacientes con EA (criterios del NINCDS-ADRDA 3-4); 14 pacientes con DMAE (criterios de Crook, GDS 2) y 16 sujetos control respecto a las estrategias de codificación de la memoria visual usando la Figura Compleja de Rey (FCR). Las diferencias intergrupales fueron estudiadas con el test de Kruskall Wallis y las correlaciones con coeficiente de Spearman. Resultados: Observamos diferencias intergrupales en el recuerdo inmediato de la FCR (KW = 7,49; p < 0,002) y en el recuerdo diferido (KW = 5,96; p < 0,05). La producción en la copia y en la evocación inmediata de la FCR presentó correlaciones negativas con el nivel de deterioro cognitivo (r = -0,70 p < 0,001). Los controles y los pacientes con DMAE mostraron alta frecuencia de uso de la estrategia sintética en el recuerdo diferido de la FCR mientras que los EA usaron mayormente estrategia no sintéticas o caóticas (x² Fisher = 3,50 p < 0,03). Conclusiones: Los resultados sugieren la mantención de las estrategias de codificación autogestadas presentes puede tener una influencia positiva sobre la memoria en el DMAE, pero es poco probable en la EA.

Escala de evaluación para enfermedad de Alzheimer: adaptación ala lengua castellana, confiabilidad interexaminadores y en retesteo seriado / Alzheimer disease assesment scale: spanish adaptation (Argentinean version), test-retest and interrater reliability

La Escala de Evaluación para Enfermedad de Alzheimer (ADAS) valora los dominios cognitivos más afectados por la enfermedad de Alzheimer (EA). Su fácil y rápida implementación hacen de ésta una de las escalas más utilizadas. Objetivo: Adaptación de ítems cognitivos, y su valoración de la reproductibilidad en el testeo seriado y de confiabilidad interexaminadores, en normal y EA. Método: La adaptación a nuestro idioma se valoró en 110 controles (edad: 59,06 + 8,90, educación 10,46 + 4,7, 42 por ciento varones, MMSE 29,3 + 0,7). Las palabras seleccionadas para las subescalas de memoria, fueron concretas y de alta frecuencia, como los objetos a nominar. Se estudió la sensibilidad y confiabilidad del testeo seriado comparando 20 pacientes con EA leve a moderada (GDS 3,35 + 1,1) y 22 controles apareados por edad y educación. Se evaluó la confiabilidad interexaminadores. Resultados: Los enfermos calificaron peor en escalas cognitiva y de memoria (p<.00001). El retest presentó alta correlación (Spearman = p<.001) en la mayoría de las variables de ambos grupos, excepto en órdenes y orientación en controles. Se descartó el efecto de aprendizaje. Se observó buena a sustancial concordancia interinvestigador (kappa.66 para subescala de memoria y .74 para subescala cognitiva). Conclusiones: Esta adaptación del ADAS es sensible y confiable. Si bien el Wilcoxon fue no significativo en ambos grupos, los valores de algunas variables del grupo control mostraron mejor rendimiento en el retesteo, por lo que debe considerarse el efecto de aprendizaje en estos (AU)

Escala de evaluación para enfermedad de Alzheimer: adaptación ala lengua castellana, confiabilidad interexaminadores y en retesteo seriado / Alzheimer disease assesment scale: spanish adaptation (Argentinean version), test-retest and interrater reliability

La Escala de Evaluación para Enfermedad de Alzheimer (ADAS) valora los dominios cognitivos más afectados por la enfermedad de Alzheimer (EA). Su fácil y rápida implementación hacen de ésta una de las escalas más utilizadas. Objetivo: Adaptación de ítems cognitivos, y su valoración de la reproductibilidad en el testeo seriado y de confiabilidad interexaminadores, en normal y EA. Método: La adaptación a nuestro idioma se valoró en 110 controles (edad: 59,06 + 8,90, educación 10,46 + 4,7, 42 por ciento varones, MMSE 29,3 + 0,7). Las palabras seleccionadas para las subescalas de memoria, fueron concretas y de alta frecuencia, como los objetos a nominar. Se estudió la sensibilidad y confiabilidad del testeo seriado comparando 20 pacientes con EA leve a moderada (GDS 3,35 + 1,1) y 22 controles apareados por edad y educación. Se evaluó la confiabilidad interexaminadores. Resultados: Los enfermos calificaron peor en escalas cognitiva y de memoria (p<.00001). El retest presentó alta correlación (Spearman = p<.001) en la mayoría de las variables de ambos grupos, excepto en órdenes y orientación en controles. Se descartó el efecto de aprendizaje. Se observó buena a sustancial concordancia interinvestigador (kappa.66 para subescala de memoria y .74 para subescala cognitiva). Conclusiones: Esta adaptación del ADAS es sensible y confiable. Si bien el Wilcoxon fue no significativo en ambos grupos, los valores de algunas variables del grupo control mostraron mejor rendimiento en el retesteo, por lo que debe considerarse el efecto de aprendizaje en estos

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%).

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.

[Hydronephrosis and peripelvic cysts. A new echographic sign for the differential diagnosis]. / Idronefrosi e cisti peripieliche. Un nuovo segno ecografico per la diagnosi differenziale.

The differential diagnosis of peripelvic cysts and hydronephrosis by means of US sometimes presents some problems; in fact, the use of urography to solve a diagnostic doubt is not uncommon. This study was aimed at demonstrating that another US sign, which we have called the "convexity" sign, can be useful in allowing peripelvic cysts to be distinguished from hydronephrosis. Thus, cysts exhibit convex walls and curved outline, whereas in hydronephrosis the walls of the dilated calices are linear. The latter feature is present in all degrees of hydronephrosis, except in severe cases. Forty-nine adult patients, a total of 98 kidneys, were examined with US and urography; 69 kidneys were found to be pathologic: 48 presented with cysts, and 21 with hydronephrosis. In addition to the new sign, the classic signs of peripelvic cysts were also considered, that is the separate areas and the non-visualization of the ureter. The sensitivity of the new sign was 97% and its specificity was 95%. The sensitivity and the specificity of the classic signs were 97% and 95%, respectively for the separated areas, and 100% and 91% for the non-visualization of the ureter. The cumulative sensitivity of the 3 signs was 99%, and their specificity 96%. Our results show how the integrated analysis of the considered signs (especially those with high specificity) is useful for the differential diagnosis, and therefore to avoid the indiscriminate use of urography.

Feasibility and efficacy of arginine 2-mercaptoethanesulfonate (ARGIMESNA) in the prevention of hemorragic cystitis from ifosfamide (IFO).

Tolerability and efficacy of the new uroprotective agent ARGIMESNA was assessed within a randomized cross-over study comparing it to sodiummercaptoethanesulfonate (MESNA), in patients treated with IFO. MESNA i.v., 20% of IFO dose, was given to all patients before chemotherapy; 4 h later, at random, they received ARGIMESNA p.o., 20% of IFO dose every 2 h x 4, or MESNA p.o., 40% of IFO dose every 4 h x 2. Overall, 78 cycles of oral uroprotection were administered: 37 for ARGIMESNA capsules; 41 for MESNA vials p.o. ARGIMESNA was subjectively better tolerated, determining gastro-intestinal discomfort in only 12 out of 37 cycles versus 34/41 of MESNA p.o. (p less than 0.001). Both preparations were equivalent for subjective and objective efficacy since no cycles were complicated by urinary symptoms (dysuria, stranguria, or hematuria). Nevertheless, 2 patients (7.7%) refused further oral assumption of both uroprotectors, whereas MESNA i.v. was added in other 7 patients because of nausea and vomiting caused by chemotherapy. In conclusion, this new oral preparation of mercaptoethanesulfonate turned out to be well tolerated, safe and active in the prevention of haemorrhagic cystitis from IFO.

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.

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.