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The effect of the intra-articular injection of radioactive erbium 169 and yttrium 90 on the growth of the leg in rabbits has been studied. I colloid state these isotopes are used clinically for synovial ablation. These beta emitters slow down bone growth in proportion to the amount of radioactivity injected. If the joint has previously been damaged by an inflammatory arthritis the effect of the radiation on the bone growth is reduced. [ABSTRACT FROM PUBLISHER]

UTERINE FIBROIDS. Uterine fibroids are the most common tumors of the female genital tract. They can be asymptomatic or associated with various symptoms like abnormal uterine bleeding, pelvic pain, pelvic or extra pelvic compressive signs, or anaemia. They can also be associated with infertility. The main further examination for fibroids diagnosis is pelvic ultrasound. Pelvic MRI (Magnetic Resonance Imaging) is also useful before surgery or interventional radiology for fibroid mapping. All fibroids must be located according to the FIGO classification. No treatment is necessary in the absence of clinical symptoms. The management of uterine fibroids depends on the clinical signs, the mapping, and the preservation of the uterus as well as fertility. Medical treatment is the first-line option. In case of failure, therapeutic options include surgery or uterine artery embolization., Competing Interests: J.-L. Brun, C. Guinard, I. Molina-Andreo et C. Bonneton déclarent n’avoir aucun lien d’intérêts. V. Bernard déclare avoir participé à des interventions ponctuelles pour IBSA, Besins Healthcare, Merck Serono et Exeltis. S. Frantz déclare avoir été prise en charge, à l’occasion de déplacements pour congrès, par les laboratoires Theramex et Gedeon Richter. J. Carrière déclare avoir été prise en charge, à l’occasion de déplacements pour congrès, par Organon et Ferring. C. Hocké déclare avoir participé à des interventions ponctuelles pour Gedeon Richter.

Nitrous oxide (N 2 O) was found responsible for genetic and reproductive toxicities, whereas it is widely used in paediatric care units where most healthcare providers are women of childbearing age. This motivated investigating occupational overexposure and overexposure factors in several paediatric hospital units. A cross-sectional study was carried out in seven healthcare units. On each of 34 healthcare providers, air samples were extracted (portable pumps and Tedlar ® bags) and N 2 O quantified (gas chromatography, pulsed discharge ionization detection, and infrared spectrometry). The data allowed calculating mean instantaneous exposures. The mean instantaneous exposure was: i) four times higher in closed vs. open treatment rooms; ii) two times higher in case of use vs. non-use of N 2 O; iii) significantly higher in junior vs. senior healthcare providers (by 12%); and, iv) higher during presumably short vs. presumably long procedures (by 20%). Overexposures to N 2 O were mainly seen in the emergency unit and in day hospitals for thoracic/abdominal diseases and nephrology. Overexposures were frequent during short-duration procedures; among 88 N 2 O measurements, 77 (87.5%) exceeded the 200 ppm threshold over 15 minutes. The overexposures call for dedicated treatment rooms (with adequate equipment and ventilation), more efficient anaesthetic practices, appropriate training, and regular checks.

Disseminated tumor cells (DTC) in bone marrow are independently related to poor outcome in patients with breast cancer. Phenotypic characterization of DTC may be useful to improve evaluation of the metastasizing potential of DTC and also to more accurately target aggressive tumor cells. DTC were screened in bone marrow aspirates from breast cancer patients by immunocytochemistry with an anticytokeratin (anti-CK) antibody (A45B/B3). Because the cell permeabilization and fixation required for intracellular CK staining is deleterious for mRNA, we used microaspiration to isolate single tumor cells stained with a monoclonal antibody directed against a membrane epitope, epithelial cell adhesion molecule (EpCAM), in CK-positive cases. Urokinase-type plasminogen activator receptor (uPAR) was quantified by real-time quantitative RT-PCR. The SKBR3 human breast cancer cell line was used to calibrate RT-PCR. A linear relationship was observed between the cycle threshold (Ct) of uPAR and 18S gene expression and SKBR3 cells spiked (1, 3, 7, 10 and 20) in control patient bone marrow. EpCAM-positive cells were aspirated in 21 out of 25 bone marrow specimens from breast cancer patients with CK-positive cells and uPAR mRNA expression was determined in 16 cases. A high level of uPAR mRNA in DTC was detected in 8 out of 16 patients (50%) and was associated with a more aggressive primary tumor phenotype (estrogen receptor [ER]-negative, progesterone receptor [PR]-negative or HER2-positive) (p = 0.01). We demonstrated that real-time quantitative RT-PCR was reliably adapted to phenotype analysis of isolated micrometastatic cells. A larger study would be useful to confirm the importance of uPAR to define higher risk subgroups of breast cancer patients with micrometastatic disease., ((c) 2004 Wiley-Liss, Inc.)

Purpose: The presence of tumor cells in bone marrow has been reported to represent an important prognostic indicator in breast cancer, but the clinical significance of circulating cells in peripheral blood is less well known. The aim of this study was to evaluate the feasibility of identifying cytokeratin (CK)-expressing cells in peripheral blood with an automat-assisted immunohistochemical detection system and to compare it with detection of tumor cells in bone marrow samples., Experimental Design: Cytospun Ficoll fractions of peripheral blood and bone marrow were obtained simultaneously in 114 breast cancer patients at different stages of the disease (I to IV) before treatment with chemotherapy. The pancytokeratin (CK) monoclonal antibody A45-B/B3 (anti-CKs 8, 18, and 19) was used for epithelial cell detection. Immunostained cells were detected by an automated cellular imaging system (ChromaVision Medical System)., Results: CK+ cells were detected in 28 (24.5%) patients in blood and in 67 (59%) patients in bone marrow. Twenty-six (93%) patients with CK-positive cells in blood also had positive bone marrow (P < 0.001). Positive cells were detected in peripheral blood in 3/39 (7.5%) operable breast cancers (stage I/II), 9 of 36 (25%) locally advanced breast cancers (stage III), and 16 of 39 (41%) patients with metastatic disease (stage IV; P = 0.017). In the subgroup of nonmetastatic patients (n = 75), prognostic factors for poor disease-free survival were: absence of estrogen receptor; presence of CK+ cells in bone marrow (P = 0.012); clinical nodal involvement; large tumor size (T4); and presence of tumor emboli. Presence of circulating CK+ cells in the peripheral blood was not statistically correlated with disease-free survival. On multivariate analysis, independent indicators for disease-free survival were: absence of estrogen receptor (P = 0.043) and presence of CK+ cells in bone marrow (P = 0.076)., Conclusions: The clinical relevance of circulating epithelial cells as a prognostic factor is not supported by the present data, especially in comparison with tumor cells in the bone marrow. However, this method of detection may be useful to monitor the efficacy of treatment in advanced or metastatic breast cancer.

The adenomatous polyposis coli (APC) gene has been found to be mutated during the development of sporadic colorectal cancers as well as in familial adenomatous polyposis (FAP). These conditions result from initially somatic and germ line mutations respectively. In both cases, the expressed protein is truncated at its carboxyterminal region. Investigations into the role of wild-type APC have led to a better understanding of the importance of mutations in the genesis and progression of adenomas. APC was shown to regulate cell growth and cell death, to bind beta-catenin, and to colocalize with microtubules. APC truncation was therefore hypothesized to alter cell multiplication and cells are no longer able to undergo apoptosis. Owing to its beta-catenin binding, APC can modify the pool of beta-catenin which is in part utilized in the assembly of adherens junctions and in nuclear signalling. Truncated APC is unable to regulate this pool thereby altering adhesion and cell signalling. Finally, APC involvement in microtubule-dependent locomotion may explain some changes in cell movement which are observed in adenomas. The establishment of murine mutants and of normal and malignant intestinal cell cultures have allowed to assess biochemical and physiological properties of APC and its putative role in the genesis of colorectal carcinogenesis. Moreover, these experimental models have suggested a variety of possible therapeutic approaches.

The adenomatous polyposis coli (APC) gene has been found to be mutated during the development of sporadic colorectal tumours as well as in familial adenomatous polyposis patients (FAP), mutations being somatic or germinal respectively. The gene product is truncated in the carboxyterminal region but the role of the APC protein in tumorigenesis is not well understood. The purpose of this review is to reassess studies on the APC protein in an attempt to understand how the loss of its functions may cause or contribute to the development of carcinomas.

Fetal bone resorption was measured by an organ culture technique using fetuses from thyroparathyroidectomized (TPTX) pregnant rats to investigate the roles of fetal and maternal hormones in the regulation of basal bone resorption in utero. Thyroparathyroidectomized female rats were treated with thyroxine and/or metabolites of vitamin D3. Basal bone resorption was greatly increased in fetuses from TPTX mothers. Administration of 1,25-dihydroxycholecalciferol or 1,24,25-trihydroxycholecalciferol to TPTX female rats normalized the basal bone resorption of the fetus whereas injection of 24,25-dihydroxycholecalciferol was without effect. Treatment of the TPTX mothers with thyroxine was also shown to normalize basal bone resorption in the fetus.

Two groups of female rats were used to investigate vitamin D metabolism in the pregnant animals and in their fetuses. In the first group, 3 micrograms of 25-hydroxyvitamin D3 (25-OH-D3) per kg of body weight were injected into intact or nephrectomized (NX) pregnant rats 3 h before sacrifice on day 21 of pregnancy; in the second group, 2 and 6 ng, respectively, of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) per day were infused continuously into pregnant rats between days 17 and 21 of pregnancy. The findings in the fetuses were obtained by quantitative analysis of extracts (Extrelut) of total fetal body lipids; the extracts were purified on Sep Pak and vitamin D sterols were further separated by high-pressure liquid chromatography. Three hours after the dams were injected with 25-OH-D3, the maternal plasma concentration (mean +/- SD) of 1,25(OH)2D3 was 221 +/- 84 pg/ml. In NX pregnant rats, the 1,25(OH)2D3 levels were still elevated: 95.6 +/- 49.0 pg/ml vs 45 +/- 22 pg/ml in control rats. In fetuses from intact or NX dams, the levels of 25-OH-D3 and 1,25(OH)2D3 were not different from the results obtained in the control fetuses but 24,25(OH)2D3 concentrations were increased (6.7 +/- 1.2 ng vs 2.2 +/- 0.7 ng/g body weight). After maternal infusion of 2 or 6 ng/day of 1,25(OH)2D3 (n = 8), plasma concentrations (mean +/- SD) of the metabolite were 64 +/- 31 and 517 +/- 356 pg/ml, respectively, the second being significantly higher than that of the control rats; 25-OH-D3 and 24,25(OH)2D3 levels did not change. 1,25(OH)2D3 contents (mean +/- SD) in fetuses from the treated dams were not different from those of control fetuses (10 +/- 2 pg/g body weight). Our results suggest that pregnant rats and their fetuses were protected against an excessive increase of 1,25(OH)2D3 concentrations in the maternal plasma; although there was some individual hypercalcemia, no significant increase in mean calcemia was detected in the dams, and 1,25(OH)2D3 either did not cross the placental barrier or was rapidly metabolized because we did not find any changes in the fetal content. As in intact or NX pregnant rats, 25-OH-D3 was metabolized into 1,25(OH)2D3, the increase of 24,25(OH)2D3 in the fetuses might be associated with a protective mechanism.

A method is described by which the action of hormones on cartilage and bone matrix in mice is ascertained by measuring 35S release from bone explants. Parathyroid extract was found to increase the rate of 35S release in vitro as well as in samples from pretreated animals, whereas calcitonin and 25-hydroxycholecalciferol were effective only in vitro.

1,25-dihydroxyvitamin D3[1,25(OH)2D3] effects on bone resorption in organ culture and on 45Ca2+ efflux rates in bone cells were measured in presence of a calcium channel inhibitor, diltiazem. Though, diltiazem reduced the 45Ca release from mice calvaria it did not act at the same Ca compartment as 1,25(OH)2D3 to alter Ca2+ flux parameters. It therefore seems difficult to hypothesize a simple relationship between bone resorption and Ca2+ movements in bone cells.

Present knowledge of the alloantigenic status of the placenta, which makes it a natural semi-allogeneic allograft is briefly surveyed. The systemic immunoregulatory mechanisms operating during normal allopregnancy which are not a prerequisite for a successful pregnancy are recalled. The placenta--dependent local mechanisms, e.g. trophoblast dependent decidual suppressor cells, factor mediated and factor independent resistance to cell mediated lysis, are surveyed as well as some of the mechanisms of action of trophoblast regulatory factors, namely suppressor cell induction and inhibition of IL-2 dependent cell growth/activation. The main feature of the CBA x DBA/2 model of spontaneous abortions in mice, and its prevention by anti Balb/c leukocyte immunisation are described. It was shown that anti-T cell depletion prevents the anti-abortive effects of immunisation. Such a treatment is also able to restore normal placental weight in auto-immune MRL lpr mice, which are known to display excess seric CSF beta-like activity (CSFs being in vitro efficient growth factors for trophoblasts). Transfer of such cells into the MHC compatible CBA/J prevents resorbtions upon a subsequent mating with DBA/2. Thus, direct effects of CSFs beta 1 and beta 2 as anti abortifacient (IL3 and GM CSF) are described together with the abortificacient effects of TNFs and NKs activators.

A method for studying in vitro bone matrix resorption by the use of 35S injection was investigated. Various hormones were tested and their effects on 35S and 45Ca metabolism were compared.