Modulatory effect of fluoride and irradiation on rat molar rate of wear

The hypothesis was tested that fluoride (F-) modulates molar wear rate in the irradiated rat and that enamel solubility and dentin hardness are involved in this process. Seventy five 21 day-old rats were divided into 5 groups. Groups received either F-(25 ppm) in the drinking water or irradiation to the head (15 Gy in a single dose), or a combination of the two. The rate of occlusal wear was assessed by computerized planimetry.The amount of wear was significantly higher in the F- and irradiation monotreated rats, while under combined treatment it did nor differ significantly from the control values. Fluoridation or irradiation suppressed enamel solubility, as measured by calcium release in the etchant. Dentin microhardness, expressed in Vickers hardness number, was enhanced after either treatment, but remained unaffected when F- administration preceded irradiation. Enamel solubility and dentin microhardness did not correlate significantly with the rate of occlusal wear.L’hypothèse vérifiée dans cette recherche a été la modulation par le fluoré (F-) de l’usure des molaires du rat irradié et de l’éventuelle contribution de la solubilité de l’émail et de la dureté dentinaire dans ce processus. Soixante-dix rats âgés de 21 jours ont été divisés en 5 groupes. Les groupes ont reçu soit 25ppm F- dans l’eau de boisson, soit une dose unique d’irradiation (15 Gy) dans la sphère cranio-faciale, soit les deux traitements combinés. Le niveau d’usure occlusale des molaires a été déterminée par planimétrie computerisée.La quantité d’usure a été plus prononcée chez les animaux recevant uniquement du F- ou une irradiation tandis que les deux traitements combinés ont été suivis par des valeurs d’usure semblables a celles mesurées chez les témoins. La solubilité de l’émail, établie selon la quantité de calcium présente dans la solution corrosive et exprimée en mg/l Ca+ +, a été réduite par chacun des deux traitements. La dureté de la dentine, exprimée en unités Vickers, a été amplifiée par chaque traitement, restant toutefois inchangée uniquement chez les animaux recevant du F- avant l’irradiation. Les resultats de l’étude corrélative entre l’usure occlusale et la solubilité de l’émail ou la dureté dentinaire n’ont pas atteint des valeurs significatives

Prediction of outcome in locally advanced breast cancer by post-chemotherapy nodal status and baseline serum tumour markers

In spite of the apparent improvement in outcome in locally advanced breast cancer, the prognosis remains dismal in many patients. The aim of this study was to define prognostic subgroups within this heterogeneous entity. Between 1990 and 1999, 104 consecutive patients with locally advanced breast cancer were treated by a multimodality programme consisting of 4–6 courses of CAF induction chemotherapy followed by surgery, breast-conserving when feasible. In most cases, chemotherapy was then resumed, up to a total of eight courses, followed by locoregional radiation therapy. Patients with hormone receptor-positive tumours received tamoxifen (20 mg day−1) for 5 years. At a median follow-up of 57 months, the 5-year overall survival for the entire group and the disease-free survival for the 94 operated patients were 65% and 53%, respectively. Univariate analysis identified 10 prognostic factors of overall and disease-free survival, of which four retained significance on multivariate analysis: inflammatory breast cancer (P=0.0000, P=0.0004, respectively), baseline tumour markers (P=0.003 for both), post-chemotherapy number of involved nodes (P=0.003; P=0.017) and extracapsular spread (P=0.052; P=0.014). In conclusion, besides inflammatory features, baseline tumour markers and post-chemotherapy nodal status are strong predictors of outcome in locally advanced breast cancer

New approaches for the prevention of rejection and graft-vs.-host disease in clinical bone marrow transplantation.

The two major barriers to successful allogeneic bone marrow transplantation (BMT) in animals and man are graft-vs.-host disease (GVHD) and the risk of graft rejection. GVHD is the result of alloreactivity of mature donor T-lymphocytes present in the graft-vs.-host tissues and can be completely prevented by pregraft depletion of T-lymphocytes. Graft rejection results from residual host immunocompetent lymphocytes that survive heavy chemoradiotherapy prior to allogeneic BMT. Host resistance to allograft cannot be eradicated even by conventional conditioning with high-dose cyclophosphamide (120 mg/kg) and lethal whole body irradiation (1,200 rad). In the present report we have utilized two new techniques to overcome GVHD and graft rejection following allogeneic BMT. GVHD can be prevented by a new monoclonal rat antihuman lymphocyte antibody, CAMPATH-1, which binds human complement, enabling donor serum to serve as the source of complement. Prevention of rejection of T-lymphocyte-depleted marrow allografts can be achieved by the application of total lymphoid irradiation (TLI) in addition to conventional chemoradiotherapy, prior to allogeneic BMT. TLI causes potent immunosuppression with minimal side effects. A combination of TLI for overcoming host resistance to allograft, and CAMPATH-1 for overcoming GVHD, leads to a relatively smooth posttransplant outcome with no evidence of GVHD and with no need for posttransplant immunosuppression

Elimination of graft-versus-host disease by in-vitro depletion of alloreactive lymphocytes with a monoclonal rat anti-human lymphocyte antibody (CAMPATH-1).

A new monoclonal rat anti-human lymphocyte antibody (CAMPATH-1) which lyses cells with autologous human complement was used for depletion of T lymphocytes from human bone-marrow allografts in vitro before transplantation in 11 high-risk patients. HLA-matched siblings were used as marrow donors. T-cell depletion was substantial when measured by E-rosette formation (0-0.18% residual T cells) and immunofluorescence with a monoclonal anti-T-cell antibody (0-0.5%). No anti-graft-versus-host disease prophylaxis was given after transplantation. Rapid engraftment was reported in all patients, and the post-transplantation course was uneventful. No signs of graft-versus-host disease developed in any of the patients, who were observed for a maximum period of 12 months. The method might be suitable for larger-scale studies in high-risk patients. The late graft failure seen in 2 patients may reflect residual host resistance uncompromised by GvHD