The investigation of actinides' internal contamination in human body makes use of a variety of techniques. In large scale screening the technique of "in vivo" evaluation of bone 241Am burden via the determination of the nuclide activity in the skull is often used. For this purpose, adequate calibration procedures and standard phantoms are needed. The present paper summarises the studies and technical procedures followed for the development of a calibration phantom based on a commercial Alderson angiographic head in which a set of 24 241Am point sources were embedded. A theoretical study was first carried out, at the ENEA Institute for Radiation Protection, using the MCNP4-B Monte Carlo code to determine the point source distribution that closely approximates a homogeneous bone contamination. The numerical models were also used to evaluate the resulting degree of approximation. The point sources were prepared at the ENEA National Metrology Institute for ionising radiation quantities and were traceable to the Italian national standard of radionuclide activity. The sources were prepared by quantitatively dispensing a liquid solution onto a plastic disc. The activity of each source was checked by gamma-ray spectrometry and the reproducibility of the activity values was determined. Each source was then placed in the optimum position in the skull, given by the Monte Carlo modelling, by a precision mechanical device. The phantom was finally used to calibrate a whole body counter operating at the ENEA Institute for Radiation Protection. The paper reports the main theoretical and experimental aspects of this work, and also discusses the results of the first calibrations.

Actinoid Series Elements↗

PubMedDate not supplied

The blockade of mineralocorticoid hormone signaling provokes dramatic teratogenesis in cultured rat embryos.

Although the administration of adrenocortical hormones to pregnant rats provokes only limited effect on the growth and development of the fetus, the direct influence of these steroids on cultured embryos has never been studied. The disruption of cell signaling by ZK 91587, which specifically occupies the mineralocorticoid receptor, resulted within 2 days in significant and pronounced adverse effects on the total length, the somite number, the embryo curvature, the communication between vitelline and umbilical blood vessels in the allantoid, and the vascularization of the vitelline sac, in 244-hour Wistar rat embryos in culture. The average score of 16 organs declined in a dose-dependent manner, following exposure to ZK 91587, and this was totally reversed by 10 microM aldosterone which, by itself, did not at all influence the embryonic development. The organogenesis was inhibited in the order: hind limb > fore limb > optic stalk > brain > olfactory pit > otic vesicle. ZK 91587 was completely ineffective in embryos that had attained the age of 260 hours. Similar, but less dramatic, results were obtained with the mineralocorticoid antagonist RU 26752, and with the antiglucocorticoid RU 38486. Sprague-Dawley rat embryos responded in a manner similar to the Wistar conceptuses. Thus, steroid receptor-mediated cell signaling is of critical importance to the growth and development of cultured rat embryos, which form a new model system to unravel adrenocortical hormone action.

Animals↗

PubMedDate not supplied

Reliability of biomarkers of iron status, blood lipids, oxidative stress, vitamin D, C-reactive protein and fructosamine in two Dutch cohorts.

Biomarkers are widely used in epidemiology, yet there are few reliability studies to assess the appropriateness of using these biomarkers for the assessment of exposure-disease relationships. The aim of the study was to assess the reliability of 20 biomarkers in serum collected from two Dutch centres (Utrecht and Bilthoven) participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) at two points several years apart. Blood samples were collected from 30 men from Bilthoven and 35 women from Utrecht. Ferritin, total iron, total iron-binding capacity, transferrin saturation, transferrin, C-reactive protein, bilirubin, cholesterol, triglycerides, apo lipoprotein-A, apo lipoprotein-B, high-density lipoproteins, low-density lipoproteins, uric acid, creatinine, reactive oxygen metabolites, the ferric-reducing ability of plasma, protein thiol oxidation, fructosamine, and vitamin D biomarkers in serum were analysed from the blood samples at the two points of time. For all biomarkers, except C-reactive protein, there were no substantial changes in the mean levels over time. Uric acid, ferritin, creatinine, HDL, and apo lipoprotein-B levels consistently showed the highest reliability for men and women (intra-class correlation = 0.69-0.86). Among women, the ferric-reducing ability of plasma, and protein thiol oxidation had poor reliability; and among men iron-related biomarkers (except serum ferritin) had poor reliability. With the exception of a few gender-specific differences, most of the 20 biomarkers performed well and can be considered to have sufficient reliability to be used in future cohort studies.

Biomarkers↗

PubMedDate not supplied

Outcome measurement from the functional status perspective.

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Community Health Nursing↗

PubMedDate not supplied

Effect of total parenteral nutrition on the protein kinetics of patients with cancer cachexia.

AIMS AND BACKGROUND: The question of whether TPN is able to reverse lean body mass depletion in cachectic cancer patients and, in particular, its effect on protein kinetics is a matter of some controversy. This study investigates the impact of TPN on protein kinetics in patients with gastric cancer. METHODS: The study involved three patients with 14-30% weight loss. They were administered a TPN regimen including 33-40 kcal/kg/day and 1.4-1.7 g amino acid/kg/day. The protein metabolism was studied before and during TPN using a stable amino acid isotope. RESULTS: Whole body protein turnover and breakdown did not change during TPN, whereas whole body protein synthesis increased from 3.39 +/- 1.04 to 6.05 +/- 0.48 g/kg/day (P = 0.03). However, the net balance, which was slightly negative prior to TPN, became positive during nutritional support. In the skeletal muscle compartment the synthesis improved with TPN (from 9.38 +/- 2.6 nmol/100 mL/min to 35.95 +/- 3.4 nmol/100 mL/min; P = 0.0143), whereas breakdown did not change significantly. CONCLUSIONS: TPN triggers a positive metabolic response in cachectic cancer patients. Whether this results in a clinical benefit for the patient requires further investigation.

Adult↗

PubMedDate not supplied

Vascular endothelial growth factor (VEGF) and other common tissue prognostic indicators in breast cancer: a case-control study.

VEGF is a specific mitogen and survival factor for endothelial cells and a key promoter of angiogenesis in physiological and pathological conditions. Nevertheless, VEGF tissue evaluation in cancer patients as a prognostic factor compared to the conventional histological and biological parameters is still controversial. In this case-control study, tissue VEGF was retrospectively determined by immunohistochemistry and related to T, N, ER, PgR, c-erbB-2, p53, MIB-1 and cyclin D1 in 129 breast cancer patients. Seventy-four of these patients had developed distant metastases postoperatively. The remaining 55 patients had remained disease-free >10 years after surgery. In 17 (13%) of the 129 patients (six with distant metastases and eleven disease-free) tissue and plasma VEGF were concomitantly evaluated. In univariate analysis no significant differences in VEGF and tumor size were found between metastatic and disease-free patients, whereas there were significant differences in N, ER, PgR, c-erbB-2, p53, MIB-1 and cyclin D1 (p ranging from 0.001 to 0.0001). In multivariate analysis VEGF showed less significance than N, ER, c-erbB-2, MIB-1 and cyclin D1 (p = 0.012, p = 0.007, p = 0.005, p = 0.005, p = 0.002 and p = 0.001, respectively). VEGF was a significant unfavorable prognostic indicator only in the N+ subset (p = 0.015), while ER (p = 0.05 and p = 0.021) and MIB-1 (p = 0.031 and p = 0.022) were significant in both the N+ and N- subgroups. In multivariate analysis in the 74 metastatic cases VEGF did not show any significance in relation to disease-free interval and overall survival from the time of mastectomy and from the time of relapse, whereas N and PgR did (p ranging from 0.018 to 0.001). In conclusion, tissue VEGF does not seem a suitable candidate to replace conventional histological and other common biological prognostic factors in breast cancer.

Adult↗

PubMedDate not supplied

Clinical use of tumor markers in the postoperative management of breast cancer patients: new concepts.

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Antigens, Tumor-Associated, Carbohydrate↗

PubMedDate not supplied

Mutations in the 11 beta-hydroxysteroid dehydrogenase type II enzyme associated with hypertension and possibly stillbirth.

The 11 beta-hydroxysteroid dehydrogenase type II enzyme (11 beta HSD2) converts cortisol into cortisone, thus preventing occupation of the non-selective mineralocorticoid receptor by glucocorticoids in the kidney. Placental 11 beta HSD2 is also thought to protect the fetus from the high maternal circulating levels of glucocorticoids. Mutations generating inactive enzymes have been described in the HSD11B2 gene in the congenital syndrome of apparent mineralocorticoid excess (AME)--a low renin form of hypertension. Recently, a mutation has been identified in a family with AME and in which there is a high incidence of stillbirths. In this study we have expressed the R374X mutation and show that the mutant is devoid of enzyme activity in intact mammalian cells expressing a significant level of the truncated protein. While this observation elucidates the cause of AME in this family the degree to which R374X also contributes to the higher incidence of failed pregnancies remains to be determined.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMedDate not supplied

Role of the ouabain-like factor and Na-K pump in rat and human genetic hypertension.

Endogenous ouabain-like factor (OLF) is present in mammal tissues and after standardized extraction procedure can be similarly quantified by two independent assays: RIA and Na-KATPase inhibition. OLF was quantified both from plasma and tissues obtained from MHS hypertensive and MNS normotensive rats, maintained under the same environmental and dietary conditions, and from plasma of healthy volunteers and essential hypertensive patients. OLF biochemical characterization shows that it behaves like ouabain except for a 1000-fold higher affinity for the ouabain low-affinity Na-KATPase isoforms than ouabain. Tissue and plasma levels of OLF are higher in MHS than in MNS rats and are not influenced by exogenous OLF sources. Plasma OLF is also increased in a subgroup of hypertensive patients. Both in rats and humans a primary cell membrane alteration affecting ion transports seems to be linked to the increased levels of OLF. An antihypertensive compound which selectively antagonizes the pressor effect of OLF and corrects the ion transport defect is under development and can represent a new pharmacological approach to the treatment of hypertension.

Adrenal Glands↗

PubMedDate not supplied

[Study of the relationships between self-injurious behavior and pain reactivity in infantile autism].

Autism can be considered as an early general developmental disorder, characterized by problems of social interaction, problems of verbal and non verbal communication, and behavioral or ideational stereotypes. However, within autism we observe a clinical heterogeneity of autistic disorders which suggests the possibility of autistic subtypes. Several authors hypothesize an analgesia among autistic children; this analgesia may be related to self-mutilation found among autistics. The current research had two objectives: 1) to develop and validate evaluation tools for measuring aggression directed towards the self (Yale-Paris Self-Injurious Behavior Scale: YAPA SIB) and pain reactivity (Pre-Linguistic Behavioral Pain Reactivity Scale: PLBPRS); instruments appropriate for autistics and capable of showing different behavioral sub-types; 2) to study in 80 autistic children pain reactivity, self-injurious behavior, and their relation in different observational situations. The results show that the scales of self-injurious behavior and pain reactivity have good discriminative capacity, good test-retest reliability, and good validity. The results suggest additionally that the apparent decreased pain reactivity observed in autistics does not derive from a real analgesia but from a different mode of pain expression related to difficulties with verbal communication, body representation and certain cognitive disorders (learning disorders, problems representing sensations and emotions, problems establishing cause-effect relationships). Additionally, there is a significant relationship between certain self-injurious behaviors and the apparent reduced pain reactivity. Interpretations of this result are presented and the possible role of stress in autism is discussed.

Autistic Disorder↗

PubMedDate not supplied

Analysis of 4-ABP-DNA adducts and p53 alterations in urinary bladder carcinoma.

BACKGROUND: Activated intermediates of 4-aminobiphenyl (4-ABP) are able to covalently interact with DNA to form adducts. There is a large body of evidence indicating that carcinogen-DNA adduct formation can be one of the cancer initiating mechanisms. MATERIALS AND METHODS: (4-ABP)-induced DNA damage in association with p53 overexpression and mutations were evaluated in specimens of urothelial bladder cancers from 106 patients. RESULTS: 4-ABP-DNA adduct levels resulted higher in smokers compared to non smokers, with a borderline statistical value. p53 nuclear overexpression was related to tumor grading, while no significant correlation with stage, 4-ABP-DNA adducts, smoking habit, and disease recurrence could be observed. Concerning molecular analysis, p53 point mutations were found in 17 of 106 cases (16%) and mutational pattern was significantly associated both with higher grade and stage, but no correlation was found with disease recurrence. CONCLUSIONS: These results suggest that other sources, in addition to tobacco smoke, may contribute to 4-ABP-DNA adducts formation in bladder tissue and that p53 expression/mutation cannot be considered a prognostic factor in bladder cancer.

Aminobiphenyl Compounds↗