Effect of novel filler particles on the mechanical and wear properties of dental composites.

OBJECTIVES: The purpose of this study was to investigate the method of producing pre-polymerized fused-fiber filler modified composite (PP-FFMC) particles and the effectiveness of incorporating these novel filler particles into dental composites. METHODS: Fused-fiber filler (FFF) blocks were impregnated with composite by two different methods. Three-point flexure tests were utilized to determine which was more effective. In order to assess the effect of the addition of PP-FFMC particles, two Bis-GMA/TEGDMA based conventional composite compositions were utilized as baselines, to which the novel particles were added. Mechanical and wear tests were performed to determine the fracture toughness, biaxial flexure strength, and in vitro wear of the materials. RESULTS: Mechanical testing showed that the addition of PP-FFMC particles decreased the strength and toughness of the conventional composites. Wear tests indicated that addition of the same particles improved the wear behavior of the conventional composites. SEM analysis of the fracture surfaces indicated that the PP-FFMC particles were incorporated without creating porosity, and that fracture was transgranular through the reinforcing particles. Microscopic flaws observed in the novel particles are the likely explanation for the observed strength and toughness values. SIGNIFICANCE:The results indicate that PP-FFMC particles have the potential to improve the wear properties of dental composites, however, they adversely affect the fracture behavior. Existing processing techniques for these particles, which introduce imperfections, limit their current usefulness.     

Allogeneic hematopoietic cell transplantation for multiple myeloma

Some patients with multiple myeloma (MM) who have undergone allogeneic hematopoietic stem cell transplants remain free of disease 5 to 13 years later-a major accomplishment for a malignancy that had been resistant to all investigational therapies. Although it will require longer follow-up to determine how many are truly cured, results for patients with MM transplanted from identical twins suggest that long-term progression-free survival is possible. While 3- to 5-year survival is similar after allogeneic or autologous stem cell transplant for MM, only allograft recipients appear to enjoy long-term disease-free survival, most likely due to an allogeneic graft-versus-myeloma (GVM) effect. The very high transplant-related mortality associated with standard allogeneic stem cell transplantation is currently the major limitation to wider use of this potentially curative treatment. The challenge for clinical investigators will be to reduce the incidence of posttransplant complications. Strategies include the use of nonablative conditioning for allografts, the administration of peripheral blood stem cells (PBSC) rather than bone marrow, and the application of more focused, targeted conditioning therapies such as bone-seeking radioisotopes.     

Plasminogen activator inhibitor 1: development of a radioimmunoassay and observations on its plasma concentration during venous occlusion and after platelet aggregation

To study the effect of plasminogen activator inhibitors (PAI) on fibrinolysis it is essential to be able to specifically measure these proteins in plasma. To this end PAI-1 was purified from cortisol- stimulated HT 1080 fibrosarcoma cells and antisera raised in rabbits. The immunologic relationship of the purified inhibitor to PAI-1 in plasma and platelet extracts was established by immunoblotting and regular and reverse fibrin zymography. Furthermore, the purified product could be immunoprecipitated with antibodies to human or bovine endothelial cell-derived PAI-1. A radioimmunoassay was developed that measures both free and tissue-type plasminogen activator (t-PA)-bound PAI-1 in plasma and has an effective range of 8 to 250 ng/mL. PAI-1 antigen levels showed a twofold increase after 20 minutes of venous occlusion, partially due to hemoconcentration. Approximately one quarter of PAI-1 before and after venous occlusion is derived from platelets. After correction for hemoconcentration and the contribution of platelets to plasma PAI-1 levels, a still significant increase in PAI-1 levels was noted during venous occlusion, which suggests that the local vascular bed releases PAI-1. Concomitant with PAI-1, t-PA antigen levels increased eightfold and fibrinolytic activity 18-fold after 20 minutes of venous occlusion. PAI-1 and t-PA levels tend to augment with age: in a group of older healthy volunteers (mean age, 53 years) PAI-1 levels were twice and t-PA levels 1.7 times higher than those in a group with a mean age of 29 years. Determination of PAI-1 antigen levels before and after platelet aggregation demonstrated that 85% of PAI-1 in platelet-rich plasma is associated with platelets. The average amount of PAI-1 per platelet was 0.3 fg/platelet, ie, 4,000 molecules per platelet.     

Non-myeloablative allogeneic haematopoietic cell transplantation for relapsed diffuse large B-cell lymphoma: a multicentre experience

Patients with relapsed diffuse large B-cell lymphoma (DLBCL) who have failed or are ineligible for autologous haematopoietic cell transplantation (HCT) have a poor prognosis. We examined the outcomes of non-myeloablative allogeneic HCT in this setting. Thirty-one patients with DLBCL and one patient with Burkitt lymphoma received allogeneic HCT following 2 Gy total body irradiation with or without fludarabine. Median age was 52 years. Twenty-four patients (75%) had undergone prior autologous HCT. Disease status at HCT was complete response (14/32, 44%), partial response (9/32, 28%), or refractory (9/32, 28%). Cumulative incidences of acute graft-versus-host disease (GVHD) grades II-IV, grades III-IV, and chronic GVHD were 53%, 19%, and 47% respectively. With a median follow-up of 45 months, 3-year estimated overall (OS) and progression-free survival (PFS) was 45% and 35% respectively. Three-year cumulative incidences of relapse and non-relapse mortality were 41% and 25% respectively. In multivariate models, chemosensitive disease and receipt of >or=4 lines of treatment before HCT were associated with better OS. Patients with chemosensitive disease had 3-year OS and PFS of 56% and 43% respectively. Non-myeloablative allogeneic HCT can produce long-term disease-free survival in patients with chemosensitive relapsed DLBCL who have failed or are ineligible for autologous HCT.     

Non-myeloablative allografting from human leucocyte antigen-identical sibling donors for treatment of acute myeloid leukaemia in first complete remission

Many patients with acute myeloid leukaemia (AML) in first complete remission (CR1) are ineligible for allogeneic transplantation as a result of age or medical problems other than leukaemia. Eighteen patients (median age 59 years, range 36-73 years) with de novo (n = 13) and secondary (n = 5) AML in morphological CR1, who were not candidates for conventional allografting, received non-myeloablative peripheral blood stem cell transplants from human leucocyte antigen identical sibling donors after conditioning with 2 Gy total body irradiation (TBI; n = 10) or 2 Gy TBI and 90 mg/m2 of fludarabine (n = 8). Postgrafting immunosuppression was with cyclosporine and mycophenolate mofetil. Two rejections were observed in patients not given fludarabine and one died with relapse. Overall, 10 patients died between 77 and 841 d, seven from relapse and three from non-relapse mortality (NRM). Day +100 NRM was 0% with a 1-year estimated NRM of 17%[95% confidence interval (CI) 0-35%]. The median follow-up among the eight survivors was 766 d (range, 188-1141 d). Seven of these eight survivors remain in complete remission (CR). One-year estimates of overall and progression-free survivals were 54% (95% CI 31-78%) and 42% (95% CI 19-66%) respectively. While follow-up is short, this analysis demonstrates that the procedure is sufficiently safe to be studied in a wider group of patients.     

Rituximab for follicular lymphoma

Treatment with the chimeric anti-CD20 antibody rituximab has been rapidly accepted into the clinical treatment of patients with CD20 positive lymphoma. The low toxicity profile, relative ease of administration, and encouraging response rates observed as a single agent allow it to be used alone or in combination with or following standard chemotherapies. Patients with follicular non-Hodgkin's lymphoma (NHL) have a high response rate to treatment with this new modality, with overall response rates of 50% to 60% in the relapsed setting and 70% in the initial setting. The addition of scheduled retreatment or maintenance therapy leads to improved clinical responses and delays time to progression. Combination trials with chemotherapy demonstrate feasibility and promising response rates including clearing of minimal residual disease detected using molecular techniques. To date, there are limited randomized clinical trial data available to guide the use of this new modality in this patient population and few long-term results. It remains difficult to determine when and how to use this new modality best in the overall treatment course of these patients. This paper discusses the rationale for the use of rituximab in patients with follicular NHL and discusses the available data involving dosing, schedule, timing, and combinations with chemotherapy.     

Foot pain: specific indications for scintigraphy

Bone scintigraphy is requested as part of the investigation of foot pain, but its contribution to clinical management has not been comprehensively documented. Previously published data are limited; the most comprehensive series identified scintigraphic abnormalities in patients with primarily orthopaedic problems and a control group was not included (Maurice HD et al. J Bone Joint Surg 1987;69B:448 52). The aim of this study was to evaluate whether bone scintigraphy may be useful in different clinical circumstances indicated by referral request details. Regions of scintigraphic abnormality were scored and compared with clinical details drawn from case notes of 60 patients with foot pain. The commonest clinical indications for scans were: confirmation of the clinical suspicion of plantar fasciitis, documentation of the extent of inflammatory arthritis and location of focal pathology. A group of 30 asymptomatic, age- and sex-matched controls were also studied. In 14 out of 19 symptomatic feet in the plantar fasciitis group, focal uptake at the medial calcaneal tubercle was present, confirming the diagnosis. In patients with non-specific, diffuse foot pain, the bone scan identified focal abnormalities in 11 out of 14 cases, thus directing the clinician to the site of pathology. Scintigraphy also proved useful in mapping local inflammatory disease. Technetium-99m methylene diphosphonate image abnormalities occurred in the control group most commonly in the midfoot (16 regions in 13 subjects) and first metatarsophalangeal joint (19 regions in 14 subjects).