Differential Diagnoses of Systemic Mastocytosis in Routinely Processed Bone Marrow Biopsy Specimens: A Review

Diagnosis of systemic mastocytosis (SM) is mainly based on the morphological demonstration of compact mast cell infiltrates in various tissue sites. In almost all patients such infiltrates are detected in the bone marrow. Reliable immunohistochemical markers for the diagnosis and grading of SM have been established, but various differential diagnoses including myeloproliferative neoplasms, basophilic and eosinophilic leukemias may be very difficult to delineate. Even more challenging is the recognition of hematological neoplasms with signs of mast cell differentiation but not fulfilling diagnostic criteria for SM, especially the rare myelomastocytic leukemia. It is also important to separate the reactive state of mast cell hyperplasia from indolent variants of SM, especially those with a very low degree of bone marrow infiltration and absence of compact mast cell infiltrates. When the lymphocytic component of the SM infiltrate is very prominent, SM may be confused with an indolent lymphoma, especially lymphoplasmacytic lymphoma which almost always shows a marked reactive increase in mast cells. In aggressive and leukemic variants of SM, mast cells may be very atypical and devoid of metachromatic granules. This hypogranulation can be regarded as cellular atypia and may lead to the misdiagnosis aspect of monocytic leukemia or histiocytic neoplasm. Regarding immunohistochemical anomalies, mast cells in aggressive and leukemic SM have been found to express CD30 (Ki1-antigen). Thus, anaplastic large cell lymphoma or Hodgkin's disease may first be considered rather than SM. There is increasing evidence that most patients with long-standing adult-type urticaria pigmentosalike skin lesions have in fact indolent SM. Therefore, such skin lesions are an important clue to the correct diagnosis in these patients. However, in aggressive or leukemic SM skin lesions are usually absent and then the correct diagnosis relies on an appropriate investigation of bone marrow biopsy specimens using both SM-related immunohistochemical markers (tryptase, KIT, CD25, CD30) but also markers excluding potential differential diagnoses. Investigation for presence of the activating KIT point mutation D816V is very helpful to establish a correct diagnosis of SM in all the difficult cases exhibiting a low degree of bone marrow infiltration or puzzling morphological findings. Copyright (C) 2010 S. Karger AG, Base

Effect of risedronate on joint structure and symptoms of knee osteoarthritis: results of the BRISK randomized, controlled trial [ISRCTN01928173]

To determine the efficacy and safety of risedronate in patients with knee osteoarthritis (OA), the British study of risedronate in structure and symptoms of knee OA (BRISK), a 1-year prospective, double-blind, placebo-controlled study, enrolled patients (40–80 years of age) with mild to moderate OA of the medial compartment of the knee. The primary aims were to detect differences in symptoms and function. Patients were randomized to once-daily risedronate (5 mg or 15 mg) or placebo. Radiographs were taken at baseline and 1 year for assessment of joint-space width using a standardized radiographic method with fluoroscopic positioning of the joint. Pain, function, and stiffness were assessed using the Western Ontario and McMaster Universities (WOMAC) OA index. The patient global assessment and use of walking aids were measured and bone and cartilage markers were assessed. The intention-to-treat population consisted of 284 patients. Those receiving risedronate at 15 mg showed improvement of the WOMAC index, particularly of physical function, significant improvement of the patient global assessment (P < 0.001), and decreased use of walking aids relative to patients receiving the placebo (P = 0.009). A trend towards attenuation of joint-space narrowing was observed in the group receiving 15 mg risedronate. Eight percent (n = 7) of patients receiving placebo and 4% (n = 4) of patients receiving 5 mg risedronate exhibited detectable progression of disease (joint-space width ≥ 25% or ≥ 0.75 mm) versus 1% (n = 1) of patients receiving 15 mg risedronate (P = 0.067). Risedronate (15 mg) significantly reduced markers of cartilage degradation and bone resorption. Both doses of risedronate were well tolerated. In this study, clear trends towards improvement were observed in both joint structure and symptoms in patients with primary knee OA treated with risedronate

Identification of nonlinearity in conductivity equation via Dirichlet-to-Neumann map

We prove that the linear term and quadratic nonlinear term entering a nonlinear elliptic equation of divergence type can be uniquely identified by the Dirichlet to Neuman map. The unique identifiability is proved using the complex geometrical optics solutions and singular solutions

Relativistic Elastostatics I: Bodies in Rigid Rotation

We consider elastic bodies in rigid rotation, both nonrelativistically and in special relativity. Assuming a body to be in its natural state in the absence of rotation, we prove the existence of solutions to the elastic field equations for small angular velocity.Comment: 25 page

Relationships between internal and external handcycle training load in people with spinal cord injury training for the handbikebattle

Objective: To establish the relationship between internal and external handcycling training load for monitoring training in people with paraplegia. Design: Observational study. Subjects: Ten people with paraplegia. Methods: All participants performed a graded peak exercise test. Power output and heart rate (HR) were measured and the session rating of perceived exertion (sRPE) was determined during a 12-week training period. Training Stress Score (TSS) was calculated from power output data, and TRaining IMPuls (TRIMP) was determined, based on HR, HRzones and sRPE. Partial correlations (for all training sessions of all participants) and Pearson’s correlations (for all training sessions of an individual participant) were performed to determine the relationship between external (TSS) and internal (TRIMPHR, TRIMPHRzones and TRIMPsRPE) training loads. Results: Partial correlations between measures of internal and external loads (r = 0.81–0.85) and correlations between TRIMPsRPE and TRIMP scores based on HR (r = 0.77–0.78) were very large. At the individual level, Pearson’s correlations varied from moderate (r=0.48) to nearly perfect (r = 0.99). Conclusion: TRIMPsRPE and TRIMPHR showed very large correlations with external training load, and thus appear appropriate for use in monitoring handcycling training load in people with paraplegia. However, it is recommended that both measures are used in combination, when possible, since some individuals showed weaker relationships