Bone lesions in elderly multiple myeloma

We investigated the incidence of bone lesions in elderly cases of multiple myeloma (MM) and the course of those lesions, and also evaluated the relationships of skeletal symptoms with prognostic factors, and prognosis. The subjects were 146 patients, aged 65 years or more (median age 74, range 65-97 year), who were admitted to 11 institutions between January, 1988 and December, 1997. They consisted of 64 men and 82 women. The disease type was IgG type in 88 patients, IgA type in 37 patients, Bence-Jones (BJ) type in 17 patients, IgD type in three patients, and non-secretory type in one patient. Bone lesions in elderly MM patients were compared with those in 65 non-elderly MM patients. Skeletal symptoms were noted in 104 patients, and bone pain in 75 patients at the time of diagnosis. The bone lesions were evaluated as only osteolytic lesions in 26 patients, osteolytic lesions + osteoporosis in 23 patients, only osteoporosis in 2 patients and pathologic bone fractures in 53 patients. The occurrence rate of osteoporosis plus osteolytic lesion was higher in elderly patients (63.5%) than that in non-elderly patients (NE-MM group) (28.3%) (p < 0.0001). The bone lesions were most often observed in lumbar vertebrae (58.7%), cranial bone (56.7%), thoracic vertebrae (40.4%) and ribs (27.9%). The occurrence rate of bone lesion in lumbar vertebrae was higher in elderly patients (58.7%) than that in non-elderly patients (22.6%) (p < 0.0001). The life activities were limited in 71 patients because of the bone lesions. The relationship between the prognostic factors of MM and bone lesions was evaluated. There was a significant difference in the serum Ca level between patients with and without bone pain (P < 0.0001) and between those with and without pathologic bone fracture (P < 0.01). There was a significant difference in the appearance rate of plasma cells in the bone marrow between the patients with and without bone lesions (P < 0.05), between those with and without bone pain (P < 0.01), and between those with and without pathologic fracture (P < 0.05). There was a significant difference in the serum beta 2-microglobulin level between the patients with and without bone pain, and between those with and without pathologic fracture. There were no significant differences in survival times between elderly MM patients with and without bone lesions, bone pain and pathological bone fractures, while significant differences of survival times were found between non-elderly MM patients with and without bone lesions, bone pain and pathological bone fractures (P < 0.05, each). These data suggest that there are some differences in bone lesions between elderly and non-elderly MM patients.     

IL-17A/F Modulates Fibrocyte Functions in Cooperation with CD40-Mediated Signaling

T helper 17 (Th17) cells that produce interleukin (IL)-17A and IL-17F have been found to participate in the development of bronchial asthma and bleomycin-induced pulmonary fibrosis. However, whether they play a causative role in the airway remodeling observed in these respiratory diseases remains unclear. Because fibrocytes are involved in tissue repair and fibrosis and are presumably precursors of lung fibroblasts and myofibroblasts, we examined the effects of IL-17A/F on fibrocyte functions. Both IL-17A and IL-17F enhanced fibrocytes’ α-smooth muscle actin expression. Priming fibrocytes with IL-17A enhanced their CD40-mediated IL-6 production, whereas IL-17F-priming increased the CD40-mediated mRNA expression of collagen I, vascular endothelial growth factor, and angiogenin. CD4⁺ T cells co-cultured with fibrocytes produced IL-17A, which was inhibited by blocking CD40 and CD40 ligand interactions. These findings suggest that cooperative interactions between fibrocytes and Th17 cells play an important role via CD40- and IL-17A/F-mediated signaling for collagen and proangiogenic factor production, which may lead to the extracellular matrix deposition and neovascularization seen in airway remodeling.     

Morphological divergence in the curvature of human femoral diaphyses: Tracing the central mass distributions of cross-sections

The diaphysis of the human femoral bone has a physiological anterior curvature; additionally, there is a curvature to the medial side or lateral side. In addition to compression stress from gravity during standing, walking, and running, these bones are continuously exposed to complex stresses from the traction forces of the various strong muscles attached to them. The femoral diaphysis is subjected to these mechanical stresses, and the direction and size of its curvature are defined according to Wolff's law and the mechanostat theory of Frost. The purpose of this study was to quantitatively evaluate the curvature of the femoral diaphysis in Japanese skeletons by determining the curve connecting the central mass distributions (CMD) of cross-sectional images. A total of 90 right femora (46 males and 44 females) were randomly selected from modern Japanese skeletal specimens. Full-length images of these bones were acquired using a clinical computed tomography scanner. The range between the lower end of the lesser trochanter and the adductor tubercle of each femur was divided at regular intervals to obtain ten planes, and nine levels were analyzed. The CMD curve was determined by connecting the CMDs of each of the nine cross-sections. First, the CMD of a cross-section in each of the nine slices was calculated, and the nine trajectories were superimposed from above. Then, by converting the shape of the entire CMD curve to superimpose the coordinates of the endpoint on the starting point, a closed arc representing the curvature of the femur was determined. For both males and females, the patterns varied from mostly medial to largely lateral curvature. The size of the curvature also varied for individuals. By analyzing only the coordinates of the vertex of the CMD curve of each femoral bone, the outlines of the diaphyseal curvatures could be recognized. The femora were thereby divided into two groups: medial bending and lateral bending. Considering males and females together, the number in the lateral-curvature group (n = 51) was larger than that in the medial-curvature group (n = 39). Moreover, the average age of the lateral-curvature group was significantly higher than that of the medial-curvature group (p < 0.05). In males, with an increase in the cortical bone proportion of the cross-sectional area, the anterior vertex of diaphyseal bending tended to be more prominent. This cortical proportion was significantly higher in the medial-curvature groups than in the lateral-curvature group (p < 0.01). The phenomena observed in this study may be related to pathophysiologies such as atypical fractures of the femur and osteoarthritis of the knee joints.     

Successful Treatment with Cyclosporine and High-Dose Gamma Immunoglobulin for Persistent Parvovirus b19 Infection in a Patient with Refractory Autoimmune Hemolytic Anemia

We describe a patient with persistent pure red cell aplasia due to human parvovirus B19 (HPVB19) infection during immunosuppressive therapy for refractory autoimmune hemolytic anemia (AIHA). The patient had been given corticosteroid (CS) and/or azathioprine for AIHA. During the course of treatment, reticulocyte count and hemoglobin levels decreased suddenly. Bone marrow aspirate showed erythroid lineage-specific aplasia with a few giant proerythroblasts, suggesting the presence of HPVB19 infection. The diagnosis of aplastic crisis due to HPVB19 infection was based on positive test results by polymerase chain reaction for HPVB19 immunoglobulin M (IgM) antibody and B19 DNA. Although splenectomy followed by administration of high-dose gamma globulin (HDIG) and plasma exchange were performed, the crisis and hemolysis recurred. Aplastic crises occurred several times when the B19 IgG result became negative and the CD4+ lymphocyte count was less than 300/microL. The patient showed complete recovery from anemia after CS was switched to cyclosporin A (CsA) and intermittent administration of HDIG. The result for B19 IgG antibody was continuously positive, and the DNA result became negative after these treatments. The results in this case indicated that concomitant administration of CsA and intermittent administration of HDIG can lead to cure of chronic anemia due to HPVB19 infection in patients with refractory AIHA.     

High incidence of subclinical peripheral neuropathy in myelitis with hyperIgEaemia and mite antigen-specific IgE (atopic myelitis): an electrophysiological study

OBJECTIVE: To study subclinical involvement of the peripheral nerves in myelitis with hyperIgEaemia and mite antigen-specific IgE (atopic myelitis: AM). MATERIAL AND METHODS: We carried out a nerve conduction study of the median, ulnar, tibial, and sural nerves in 21 patients with AM and in 28 patients with clinically definite or laboratory-supported definite multiple sclerosis (MS). RESULTS: The patients with AM showed a significantly higher frequency of abnormal records than the MS patients in the sensory nerve conduction study (52.4% vs. 14.3%, p = 0.0106). The frequency of abnormal records in the motor nerve conduction study in AM patients was twice as high as in MS patients (38.1% vs. 17.9%), but the difference was not statistically significant. Abnormality in the F-wave-evoked frequency in the median nerve was also significantly more common in AM patients than in MS patients (57.9% vs. 10.7%, p = 0.0016). CONCLUSIONS: These findings suggest that subclinical peripheral neuropathy is frequent in patients with AM.