Review: Nutritional ecology of heavy metals.

The aim of this review is to focus the attention on the nutrition ecology of the heavy metals and on the major criticisms related to the heavy metals content in animal feeds, manure, soil and animal-origin products. Heavy metals are metallic elements that have a high density that have progressively accumulated in the food chain with negative effects for human health. Some metals are essential (Fe, I, Co, Zn, Cu, Mn, Mo, Se) to maintain various physiological functions and are usually added as nutritional additives in animal feed. Other metals (As, Cd, F, Pb, Hg) have no established biological functions and are considered as contaminants/undesirable substances. The European Union adopted several measures in order to control their presence in the environment, as a result of human activities such as: farming, industry or food processing and storage contamination. The control of the animal input could be an effective strategy to reduce human health risks related to the consumption of animal-origin products and the environmental pollution by manure. Different management of raw materials and feed, animal species as well as different legal limits can influence the spread of heavy metals. To set up effective strategies against heavy metals the complex interrelationships in rural processes, the widely variability of farming practices, the soil and climatic conditions must be considered. Innovative and sustainable approaches have discussed for the heavy metal nutrition ecology to control the environmental pollution from livestock-related activities.

The O3-Vet project: integration of a standard nomenclature of clinical terms in a veterinary electronic medical record for veterinary hospitals.

In order to improve the hospital information system of the Chilean University Hospital, the Veterinary Medicine School of Universidad de Chile made a research cooperation with Università San Raffaele Roma to develop and test a new release of the O3-Vet software application. O3-Vet was selected by the Chilean University mainly for two reasons: (1) it uses human medicine standardized technologies such as "Health Level 7" (HL7) and "Integrating the Healthcare Enterprise" (IHE), which allow a good level of data sharing and hospital management; (2) it is open source, which means it can be adapted to specific hospital needs. In the new release, a subset of diagnostic terms was added from the "Systematized Nomenclature of Medicine Clinical Terms" (SNOMED CT), selected by the "American Animal Hospital Association" (AAHA) to standardize the filing of clinical data and its retrieval. Results from a limited survey of veterinarians of the University (n=9) show that the new release improved the management of the Chilean University Hospital and the ability to retrieve useful clinical data.

Maternal functional speech to children: a comparison of autism spectrum disorder, Down syndrome, and typical development.

Children with developmental disabilities benefit from their language environment as much as, or even more than, typically developing (TD) children, but maternal language directed to developmentally delayed children is an underinvestigated topic. The purposes of the present study were to compare maternal functional language directed to children with two developmental disabilities--autism spectrum disorder (ASD) and Down syndrome (DS)--with TD children and to investigate relations of maternal functional language with child language skills. Participants were 60 mothers and their children with TD (n = 20), DS (n = 20), or ASD (n = 20). Children's mean developmental age was 24.77 months (SD = 8.47) and did not differ across the groups. Mother and child speech were studied during naturalistic play. We found (a) similarities in maternal functional language directed to the two groups of children with developmental disabilities compared to that directed to TD children and (b) a positive association between subcategories of information-salient speech and child mean length of utterance in TD dyads only. The clinical and developmental implications of these findings are discussed.

The O3-Vet project: a veterinary electronic patient record based on the web technology and the ADT-IHE actor for veterinary hospitals.

A veterinary electronic patient record, compliant with the IT standards (HL7, DICOM and IHE), was developed at the School of Veterinary Medicine, University of Milan (Italy) in order to improve the veterinary hospital workflows, making the stored clinical data more homogenous and sharable, thereby increasing the integration with current and future software applications. The system was developed by open-source software in order to reduce the implementation and maintenance costs and to make the system sharable with other veterinary hospitals or research centers without additional costs. The system was tested from May to October 2006. Results show that the majority of the veterinarians involved in the test agreed on the advantages obtained by the use of application software concerning the availability of all the useful clinical data [71.4%], the quality of the diagnostic procedures [78.58%] and the efficiency [85.58%] of hospital activities.

Use of the ratio of time to progression following first- and second-line therapy to document the activity of the combination of oxaliplatin with 5-fluorouracil in the treatment of colorectal carcinoma.

BACKGROUND: It has been proposed that the activity of a second-line treatment regimen can be documented by showing that the time to progression (TTP) following second-line therapy is longer than the TTP following first-line therapy in the same patients. PATIENTS AND METHODS: The ratio of TTP during first and second-line therapy, identified as the growth modulation index (GMI), was determined in 34 patients with advanced colorectal cancer. First-line chemotherapy consisted of one of several schedules of leucovorin (LV)-modulated 5-fluorouracil (5-FU) or raltitrexed. Second-line therapy consisted of the combination of LV-modulated 5-FU and oxaliplatin (1-OHP). Patients were switched to second-line therapy upon evidence of progressive disease following first-line therapy. RESULTS: Median TTP following first-line therapy was 13 weeks (95% confidence interval (CI): 7.6-18.7), while median TTP following second-line therapy was 31 weeks (95% CI: 21.3-41.0). Sixteen patients (47%; 95% CI: 35%-59%), showed a GMI > or = 1.33, while the remaining 18 patients (53%; 95% CI: 40%-66%) had a GMI < 1.33. Log-rank analysis of the Kaplan-Meier curves of TTP following first- versus second-line therapy demonstrated a statistically significant difference in favour of second-line therapy (P = 0.0081). CONCLUSIONS: This study demonstrates the utility of the GMI as a tool for assessing the activity of novel second-line therapeutic programs.

bcl-2 but not p53 expression is associated with resistance to chemotherapy in advanced breast cancer.

Programmed cell death is an important determinant of the response to chemotherapy. Among the factors controlling this process, a significant role is played by bcl-2 and p53, the expression of which, together with estrogen receptor content and tumor proliferative activity, was investigated by means of immunohistochemistry in 55 advanced breast cancer patients (median age, 60 years; range, 25-71 years). Analysis of bcl-2 expression identified two groups of patients with a significant difference in response rate. A total of 17 patients (31%) responded to chemotherapy (5 had a complete response and 12 had a partial response): 14 of 32 (44%) bcl-2-negative patients (< 40% stained cells) and only 3 of 23 (13%) bcl-2-positive patients (> or = 40% of stained cells; P = 0.019 by Fisher's exact test). The two groups were well balanced in terms of age, performance status, disease-free survival, menopausal status, and type of chemotherapy. bcl-2-negative tumors showed a tendency toward a higher p53 expression and proliferation rate, whereas an excess of bone as the dominant disease site was evident among the bcl-2-positive ones. However, the only variable to result significantly different between the two groups was estrogen receptor expression (P = 0.004). A multivariate logistic regression model showed that bcl-2 maintained its power of discriminating two groups with a different probability of responding to chemotherapy, although the greatest contribution was given by dominant disease site and type of chemotherapy. In conclusion, the results of this study suggest a possible role for bcl-2 in predicting resistance to chemotherapy.

Inductively coupled plasma mass spectroscopy quantitation of platinum-DNA adducts in peripheral blood leukocytes of patients receiving cisplatin- or carboplatin-based chemotherapy.

Platinum-DNA adducts can be assayed in peripheral blood leukocytes by means of atomic absorption spectroscopy and ELISA, and high adduct levels have been correlated previously with favorable clinical response to platinum-based chemotherapy. Our purpose was to study adduct formation in peripheral blood leukocytes by means of a new method, inductively coupled plasma mass spectroscopy (ICP-MS), and to correlate adduct formation with clinical response and toxicity. Platinum (Pt)-DNA adducts were measured by means of ICP-MS in leukocytes of 66 patients receiving a cisplatin- or carboplatin-based chemotherapy, collected either before the beginning of treatment and incubated in vitro with cisplatin or 1 and 24 h after the administration of drug to the patient. The Pt-DNA adduct level in leukocytes from patients exposed to drug in vitro was 14.33 +/- 14.71 fmol/microgram DNA (mean +/- SD), which was not significantly different from the value of 23.4 +/- 19.53 fmol/microgram DNA observed in leukocytes from nine healthy volunteers. In samples collected after the administration of chemotherapy, Pt-DNA adducts ranged from 1.91 +/- 3.59 fmol/microgram DNA (mean +/- SD) at the 1-h time point to 2.61 +/- 3.35 fmol/microgram DNA at 24 h (P > 0.05). Adduct levels in leukocytes exposed in vitro did not correlate with adduct levels from patients treated with cisplatin-based chemotherapy (r = 0.085 and 0.011 at 1 and 24 h, respectively). At 24 h, adduct levels in patients receiving cisplatin (3.15 +/- 3.64 fmol/microgram DNA, mean +/- SD) were significantly higher (P = 0.02) than those observed in patients treated with standard dose carboplatin (0.57 +/- 0.73 fmol/microgram DNA) and also higher than those in patients receiving high-dose carboplatin (1.18 +/- 1.06 fmol/microgram DNA), although the latter difference did not reach statistical significance (P = 0.071). No differences in adduct levels (mean +/- SD) were evident between patients responsive (3.23 +/- 3.51 fmol/microgram DNA) and nonresponsive (2.34 +/- 3.01 fmol/microgram DNA) to chemotherapy. In the homogeneous group of patients treated with combination of cisplatin and 5FU, received dose intensity, hemoglobin decrease, and posttreatment creatinine could not be linked with the extent of leukocyte adduct formation. The data presented here demonstrate that ICP-MS allows the detection of adducts in patients treated with cisplatin or carboplatin and suggest that adduct formation in leukocytes is not a major determinant of response or toxicity.

[The radiocesium level in children from Byelarus]. / Livello di radiocesio in ragazzi provenienti dalla Bielorussia.

In 1994, the Institute of Applied Physics of Milan carried out a study to measure cesium 137 levels in some boys and girls from Belarus, mainly the Gomel district, which is still a risk area for radioactive contamination. In the summer, nearly 700 boys and girls (age range: 8-14 years) were accommodated by some Italian families in Piedmont and Lombardy. Our research was just meant to collect some pieces of information and dealt with whole body counter measurements (70 children) and with the analysis of radiocesium levels in urine samples (50 children). Our Institute collaborated with the Service of Radiation Protection in Ispra and with the ENEL Service of Radiation Protection in Trino Vercellese. In all, we examined 70 children, divided in groups of 8-10 children each. The results of our measurements show that radiocesium levels ranged from about ten Bq to some thousands Bq. In some children who exhibited high radiocesium levels, its distribution in the body was also studied and shown to be uniform. Finally, the comparison between body and urine Cesium levels allowed us to calculate the biological half-life of soluble cesium.

Tumor proliferative activity and response to first-line chemotherapy in advanced breast carcinoma.

The relationship between tumor proliferative activity and response to first-line chemotherapy and survival was investigated in 76 advanced breast cancer patients. Proliferative activity was determined by means of Ki-67 immunohistologic staining on primary tumors (55 patients) or at the relapse site (21 patients), and was classified as low ( < or = 25% of stained cells) or high ( > 25% of stained cells). The usual WHO response criteria were used. The median duration of follow-up was 18 months (range 3-58). Forty-seven patients (62%) had tumors with low, and 29 (38%) had tumors with a high rate of proliferative activity. The two groups were well balanced in terms of important variables such as disease-free survival, performance status, age, menopausal status, and the type of first-line chemotherapy (anthracycline-based regimens versus cyclophosphamide-methotrexate-5-fluorouracil). The estrogen receptor (ER) content, measured by means of immunohistochemical assay, was markedly different in the two groups, with 27/47 tumors with low proliferative activity (57%) and 6/29 with high-proliferative activity (21%) being ER positive ( > or = 45% of stained cells) (p = 0.003). Moreover, a significant difference in the metastatic pattern was also evident, with a higher incidence of bone and a lower incidence of soft tissue metastases in the group of patients with tumors with low proliferative activity (p = 0.004). Overall, 10/47 responses (21%: PR = 7, and CR = 3) were observed in the group with a low rate of proliferative activity, versus 14/29 (48%: PR = 9, and CR = 5) in the group with highly proliferative tumors, the difference being statistically significant (p = 0.03). When a multivariate analysis was performed, the only factor that retained independent prognostic significance was the predominant site of disease, particularly soft tissues (p = 0.003). Despite the difference in response rate, when survival analysis was performed according to the Kaplan-Meier method, no significant difference was observed in the two groups, but when the analysis was limited to responsive patients, the median survival observed in those with a low and those with a high rate of proliferation was 35 and 19 months respectively (p = 0.02). The same results were obtained when multivariate survival analysis was carried out using Cox's regression model. These data suggest that there is a link between tumor proliferative activity and response to chemotherapy in advanced breast cancer, and may indicate the need to use more intensive treatments in selected patients with highly proliferative tumors.

[The use of monoclonal antibodies that recognize the neural cell adhesion molecule (NCAM) in the diagnosis of bone marrow localization of small cell lung cancer]. / L'uso di anticorpi monoclonali che riconoscono la neural cell adhesion molecule (NCAM) nella diagnosi delle localizzazioni midollari di microcitoma polmonare.

We have used immunocytochemistry to identify tumor cells in bone-marrow aspirates of 40 untreated patients with small cell lung cancer and we compared the results with conventional histomorphology. The monoclonal antibodies (MAbs) used were NCC-LU-243 and NCC-LU-246 (both cluster 1). For each MAb 76 slides were evaluated. Sixty bone-marrow biopsies were also obtained from these patients. The positivity rate between the 2 MAbs was not statistically different (46% for NCC-LU-246 and 43% for NCC-LU-243). Bone-marrow biopsies detected tumor localization in 8/60 specimens (13%), significantly less than immunocytochemistry with anti-NCAM MAbs (p = 0.003). Moreover, bone-marrow aspirates were positive for cluster 1 antigen in 6/16 patients with limited disease at diagnosis. The results confirm that NCC-LU-243 and NCC-LU-246 have equivalent ability to identify bone-marrow involvement; immunocytochemistry appears to be better suited for this purpose than conventional bone-marrow biopsy; a non-negligible proportion of patients with "limited disease" might be understaged; the clinical value of detecting bone marrow involvement by immunocytochemistry is still unclear.

AFP and HCG in germ cell tumors.

The high specificity and sensitivity of testicular tumor markers make them particularly useful in the management of these neoplasms. Basal value represents an independent prognostic variable, influencing the choice of therapy. An increase in marker level before chemotherapy could also acquire a powerful prognostic significance. The decay curve pattern is indicative of the radicality of surgery. Also during chemotherapy the behavior of markers conditions further therapeutic strategies.

A primitive lymphoma of the uterine cervix. Case report.

A case of primitive lymphoma of the uterine cervix is discussed. After two years of vaginal post-coital bleeding, the echography showed the presence of a supraisthmic mass. The patient underwent a total hysterectomy with bilateral salpingo-oophorectomy. The histology was consistent with a B-cell non-Hodgkin's lymphoma (NHL), follicular centre derived. The patient was staged as IIE and treated with six cycles of chemotherapy (CHOP), achieving a complete remission. The paper stresses the value of histology in the diagnosis of lymphoma of the uterine cervix and the effectiveness of the treatment, and reviews the relevant literature.