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[Bone marrow scintigraphy using radiocolloids in bone metastases. Sensitivity, specificity, reliability and indications].

The sensitivity and specificity of bone marrow scintigraphy in demonstrating skeletal metastases was examined in 40 patients with focal metastases. Radiology and MDP scintigraphy were used as reference methods. Sensitivity depends on the region of the skeleton. False negatives are the rule in parts of the skeleton containing little bone marrow. In relation to the entire bone marrow content, sensitivity is 0.64. The high proportion of false negatives (36%) in the presence of confirmed metastases and the incomplete demonstration of the bone marrow makes marrow scintigraphy unsuitable as a screening method. Occasionally lesions confined to the marrow can be demonstrated when radiographs and bone scintigrams are still negative. In advanced cases, marrow scintigraphy can demonstrate the extent of destruction of the bone marrow. Demonstration of displacement or of an 'empty bone' is evidence of invasion of the bone marrow in patients with tumours. In patients with reduced haematopoiesis of unknown origin or unidentified diffuse skeletal uptake, bone marrow scintigraphy may provide valuable information.

Adult↗

A rabbit bone marrow model system for evaluation of cytotoxicity: characterization of normal bone marrow cell cycle parameters by flow cytometry.

Characterization of a rabbit model system for the study of cell cycle effects of myelotoxic agents in normal bone marrow is described. Cell cycle phase distributions are obtained by computer analysis of flow cytometric single cell DNA histograms. Comparison of marrow aspirates with marrow samples from sacrificed animals indicates that dilution of aspirates with peripheral blood is not significant. Aspiration of marrow from one bone does not affect the cell cycle distribution of unsampled bones. Hence, sequential aspirates of different bones in a single animal may be used as representative samples for further study of effects of myelotoxins on marrow proliferation and differentiation.

Animals↗

The effect of treatment with budesonide or PGE2 in vitro on allergen-induced increases in canine bone marrow progenitors.

Increased bone marrow granulocyte-macrophage colony forming units (GM-CFU) in dogs developing allergen-induced airway hyperresponsiveness can be accounted for by a factor(s) present in serum following the allergen challenge. The present study evaluated whether in vitro treatment of bone marrow with budesonide or prostaglandin (PG)E2, prevents allergen-induced bone marrow stimulation. Eight dogs were studied after allergen and diluent inhalation challenges. Budesonide (10[-7] M) or PGE2 (10[-6] M) was added to bone marrow aspirated 24 h after challenge. Budesonide or PGE2 was also added to bone marrow aspirated before challenge, to which serum taken 24 h after challenge was subsequently added. Non-adherent mononuclear bone marrow cells were incubated in the presence of the serum and granulocyte/macrophage colony stimulating factor (GM-CSF), granulocyte stimulating factor (G-CSF), or stem cell factor (SCF), and the number of GM-CFU counted. Allergen-induced increases in the number of GM-CFU in bone marrow aspirated 24 h after allergen (P < 0.001) were not attenuated by budesonide or PGE2 treatment (P > 0.05). However, GM-CFU increases in bone marrow aspirated before challenge and incubated with post-allergen challenge serum (P < 0.001) were blocked by either budesonide or PGE2 (P < 0.001). These findings demonstrate that budesonide and PGE2 can act directly on the bone marrow, preventing allergen-induced increases in inflammatory cell progenitor production. This suggests that the bone marrow must be considered as a possible site of action for drugs which attenuate allergen-induced asthmatic responses.

Allergens↗

[Suppression by bone marrow cells of the level of specific IgE antibodies in the blood of mice and decrease in the production of IGE by bone marrow cells].

Changes in the level of the specific IgE-antibodies to ovalbumin under the influence of syngeneic cells of a bone marrow were studied. The IgE-response was induced by ovalbumin in mice (CBA X C57Bl/6)F1. The bone marrow cells suspensions (20-30 X 10(6) cells per mouse) from syngeneic donors was inoculated simultaneously with the immunization. It was found that bone marrow cells suppressed both the level of IgE-antibodies in experimental mice serum and the production of IgE by the bone marrow cells of the recipient. The ability to suppress IgE-response remained when erythrocytes, monocytes and T-lymphocytes were removed from inoculated suspensions. The bone marrow cells taken from the mice immunized with ovalbumin, at the stage of a decreasing IgE-response, provided more pronounced suppression, than bone marrow cells taken from intact animals.

Animals↗

Radiological evidence of lymphatic drainage of bone marrow cavity in long bones.

Injection of Lipiodol UF into the distal epiphyses of tibia and femur in the dog was followed within several minutes by visualization of lymphatics draining the bone. Some of the radioopaque material was retained in the bone marrow cavity and tiny lymph vessels originating in that area could be seen. Contrast medium filled also the popliteal lymph node. The problem of migration of bone marrow lymphocytes through the lymphatics to the regional lymph nodes is discussed.

Animals↗

Bone marrow and peripheral blood lymphocyte phenotype in patients with bone marrow failure.

Patients with aplastic anemia (AA) respond to immunosuppressive therapy, and several lines of laboratory evidence support a role for cell-mediated immunity in the pathogenesis of marrow failure including expansion of cytotoxic T lymphocytes (CTL) in the blood of AA patients, overexpression of inhibitors such as IFN-gamma in the marrow of AA patients, and suppression of hematopoietic cells by CTL in vitro. However, the phenotype of immune effectors in the marrow of AA patients remains unknown. We examined severe (sAA) and moderate AA (mAA) patients and compared them to healthy volunteers and patients with myelodysplastic syndrome (MDS). Our study shows that percentages of HLA-DR+ CD8+ lymphocytes and natural killer (NK) cells, CD56+, were elevated in the marrow of AA patients. Peripheral blood (PB), in all instances, did not reflect changes seen in the bone marrow (BM). Increased percentages of activated CD8+ cells were found in marrow and blood in 43% of AA patients, but in 28% of AA patients, activation of CD8+ cells was only detectable in the marrow. During hematopoietic recovery, activated CD8+ cells and NK cells in marrow declined, but not to normal levels. T cells bearing the gamma delta-phenotype were elevated in the blood of sAA patients (p < 0.05) but were not significantly increased in BM from sAA and MDS patients. Percentages of activated immune effectors are increased in the marrow of AA patients as is consistent with a localized immune response in this disease. Marrow phenotyping may be more sensitive than peripheral blood analysis for detecting an abnormal cellular immune response.

Anemia, Aplastic↗

Outcome for patients who relapse after allogeneic bone marrow transplantation for chronic myeloid leukemia. Chronic Leukemia Working Party. European Bone Marrow Transplantation Group.

We studied the clinical course of 130 chronic myeloid leukemia (CML) patients (89 males and 41 females) in the European Bone Marrow Transplantation Group (EBMT) registry who received transplants before January 1, 1988 and who subsequently had evidence of recurrent leukemia. All patients had received a pretransplant conditioning regimen including total body irradiation (TBI). The first evidence of relapse was cytogenetic only in 74 (57%) patients and hematologic in 56 (43%). The overall actuarial survival from relapse was 36% at 6 years, with a significantly higher proportion of survivors among female patients (53% v 30%; P < .002). In univariate analysis, the 6-year probability of survival was 52% for patients with cytogenetic relapse and 30% for patients relapsing in chronic phase (CP), while no patient who relapsed in advanced phase (AP or BC) survived more than 3.5 years from relapse (P < .0001). The actuarial survival of patients relapsing before 6 months, between 6 and 12 months, and later than 12 months after transplant was 27%, 26%, and 45%, respectively (P < .002). Among patients with cytogenetic relapse, partial or complete disappearance of Ph-positive cells occurred in 40% of untreated patients and in 42% of those treated with interferon (IFN). However, IFN therapy significantly delayed progression toward hematologic disease. Cytogenetic responses were observed in 25% of patients who received IFN for relapse into CP, while only one minor cytogenetic response was reported in patients on conventional chemotherapy. For patients presenting with cytogenetic relapse as well as for those in hematologic relapse, IFN therapy significantly improved the 2-year probability of survival. However, long-term survival for IFN-treated patients in either group was not different from long-term survival in comparable patients not receiving IFN therapy. Twenty-nine patients of this series underwent a second bone marrow transplant (BMT) and the projected survival at 4 years after the second transplant is 28%. In multivariate Cox regression analysis, four factors remained significantly associated with survival: disease phase at relapse (P < .0001), duration of time interval from BMT to relapse (P = .0001), interferon therapy at relapse (P = .0024), and patient sex (P = .0032). This retrospective study provides evidence that some patients who relapse after BMT may benefit from treatment with IFN; a second BMT may offer the chance of cure. Data from this analysis may be useful in designing future prospective trials on posttransplant CML relapse.

Adolescent↗

Bone lesions with soft-tissue mass: magnetic resonance imaging diagnosis of lymphomatous involvement of the bone marrow versus multiple myeloma and bone metastases.

Bone metastases from solid primary tumors, as well as multiple myeloma and secondary lymphoma may all present with bone lesions and associated soft-tissue masses on magnetic resonance images of the spine. In bone metastases and myeloma, the cortex of the affected bone is usually destroyed and a bulging contour is observed at the site of extraosseous spread. In cases of lymphomatous involvement of the bone marrow, however, we have observed that spread to the extraosseous soft-tissues occurs without alteration of the shape or contour of the affected bone. In order to assess whether this pattern of spread is indeed suggestive or even diagnostic of lymphoma of the bone marrow, we reviewed spinal bone marrow MR images of 66 patients, with bone metastases from solid primary tumors (33 patients), multiple myeloma (20 patients) and stage IV lymphoma with bone marrow involvement (13 patients), who had bone lesions and contiguous soft-tissue masses. If tumor was present on either side of the bony cortex but the contour of the affected bone was preserved, a "wrap-around" sign was diagnosed. A "wrap-around" sign was found in 12 of the 13 patients with lymphoma but in none of the patients with metastases or myeloma. On MR images of the bone marrow, the demonstration of tumor spread beyond the bony cortex without disruption of the outline of the diseased bone may favor the diagnosis of lymphoma more than that of metastases or multiple myeloma.

Adolescent↗

Osteogenesis after bone and bone marrow transplantation. The ability of ceramic materials to sustain osteogenesis from transplanted bone marrow cells: preliminary studies.

The ability of four different ceramic materials to support osteogenesis when placed with bone marrow into an intermuscular site was studied. In the search for biodegradable porous ceramic materials that could be used for bone replacement and that would slowly be replaced by bone by means of "creeping substitution," the authors fabricated porous alumina, calcium aluminate, calcium hydroxyapatite, and tricalcium phosphate. Specially shaped compacts, impregnated with autologous bone marrow, were inserted into intermuscular pouches in rabbits and retrieved after 14-182 days. Newly formed bone was found within the contents of the well after 14 days and was visible at all times up to 182 days. The bone was frequently found to have adhered to the ceramic and to have penetrated the interior if the pore size was greater than 100 micron. Further investigation of the use of synthetic materials in bone replacement is warranted due to the finding that some porous ceramic material permit bony ingrowth from autologous marrow cells.

Aluminum↗

The use of bone marrow cells grown in long-term culture for autologous bone marrow transplantation in acute myeloid leukaemia: an update.

Eleven patients with acute myeloid leukaemia have been transplanted with autologous marrow grown in long-term bone marrow culture. In the high risk group (six patients who had all previously relapsed) the procedure induced a remission in two patients who were in florid relapse at the time of the transplant. Five patients were transplanted in first remission and they remain well and disease-free between 150 and 12 weeks after their autologous transplant.

Adolescent↗

Alveolar bone marrow as a cell source for regenerative medicine: differences between alveolar and iliac bone marrow stromal cells.

UNLABELLED: We isolated and expanded BMSCs from human alveolar/jaw bone at a high success rate (70%). These cells had potent osteogenic potential in vitro and in vivo, although their chondrogenic and adipogenic potential was less than that of iliac cells. INTRODUCTION: Human bone marrow stromal cells (BMSCs) have osteogenic, chondrogenic, and adipogenic potential, but marrow aspiration from iliac crest is an invasive procedure. Alveolar BMSCs may be more useful for regenerative medicine, because the marrow can be aspirated from alveolar bone with minimal pain. MATERIALS AND METHODS: In this study, alveolar bone marrow samples were obtained from 41 patients, 6-66 years of age, during the course of oral surgery. BMSCs were seeded and maintained in culture with 10% FBS and basic fibroblast growth factor. In addition, BMSCs were induced to differentiate into osteoblasts, chondrocytes, or adipocytes in appropriate medium. RESULTS AND CONCLUSION: From a small volume (0.1-3 ml) of aspirates, alveolar BMSCs expanded at a success ratio of 29/41 (70%). The success rate decreased with increasing donor age, perhaps because of age-dependent decreases in the number and proliferative capacity of BMSCs. The expanded BMSCs differentiated into osteoblasts under osteogenic conditions in 21-28 days: the mRNA levels of osteocalcin, osteopontin, and bone sialoprotein, along with the calcium level, in alveolar BMSC cultures were similar to those in iliac cultures. However, unlike iliac BMSC, alveolar BMSC showed poor chondrogenic or adipogenic potential, and similar differences were observed between canine alveolar and iliac BMSCs. Subsequently, human alveolar BMSCs attached to beta-tricalcium phosphate were transplanted into immunodeficient mice. In transplants, new bone formed with osteoblasts and osteocytes that expressed human vimentin, human osteocalcin, and human GAPDH. These findings suggest that BMSCs have distinctive features depending on their in vivo location and that alveolar BMSCs will be useful in cell therapy for bone diseases.

Adipocytes↗

Differentiation of functionally active mouse T lymphocytes from functionally inactive bone marrow precursors II. Limited recovery of T-cell responses from mouse bone marrow in tissue culture.

The limited differentiation of mature T cell function from mouse bone marrow in tissue culture is described and compared with similar differentiation occuring in vivo in irradiated bone marrow protected mice. Data are presented to show that a pool of precursors, similar in size to that able to produce early (transient?) regeneration in thymectomized recipients, is responsible for the development of mitogen responsive T cells active in MLC (proliferation) and CML (development of cytotoxic cells) assays. In contrast, a helper cell population which augments antibody formation from T-depleted normal spleen cells derives from a pool of similar precursors yet does not seem to be theta positive. Similarly, larger cells (perhaps typical of those giving rise to suppressor T cells in vivo) give rise to a suppressor cell pool after 4 days of culture, though again only a fraction of this suppressor activity could be attributed to theta positive cells. It is suggested that much of the data for regenration of T lymphocytes in vitro from T-depleted sources needs to be re-interpreted in terms of this evidence for a pool of post-thymic precursors of T cells in such T-deficient cell populations.

Animals↗