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In the late 1980s, a promising new treatment for breast cancer emerged: high-dose chemotherapy with autologous bone marrow transplantation or HDC/ABMT. By the 1990s, it had burst upon the oncology scene and disseminated rapidly before having been carefully evaluated. By the time published studies showed that the procedure was ineffective, more than 30,000 women had received the treatment, shortening their lives and adding to their suffering. This book tells of the rise and demise of HDC/ABMT for metastatic and early stage breast cancer, and fully explores the story's implications, which go well beyond the immediate procedure, and beyond breast cancer, to how we evaluate other medical procedures, especially life-saving ones. It details how the factors that drove clinical use - patient demand, physician enthusiasm, media reporting, litigation, economic exploitation, and legislative and administrative mandates - converged to propel the procedure forward despite a lack of proven clinical effectiveness. It also analyses the failure of the technology assessments and randomised clinical trials that evaluated the procedure and the ramifications of this flawed system on healthcare today. Sections of the book consider the initial conditions surrounding the emergence of the new breast cancer treatment, the drivers of clinical use, and the struggle for evidence-based medicine. A concluding section considers the significance of the story for our healthcare system.

Background: Bone Marrow Aspirate (BMA) allows the study, staging and monitoring of multiple conditions with bone marrow involvement. The BMA report is a crucial component of the post-analytical stage and significantly influences the veterinarian's understanding and decision-making process. Objective: To describe the zoographic, clinical, and quality characteristics of BMA reports, as well as the frequency of diagnoses and associated factors in dogs and cats treated at veterinary centers in Colombia from 2012 to 2023. Methods: This was a cross-sectional descriptive study. Data on zoographic and clinical variables were extracted from BMA reports and consultations; the frequency of diagnoses and associated factors were determined. Adherence to reporting quality was evaluated using established guidelines for BMA in dogs, cats, and humans. Results: A total of 135 BMA reports were reviewed from eight veterinary institutions: 116 for dogs and 19 for cats, with a mean age of 5.22 ± 3 years; 53% were males. The most common indication for BMA was anemia, alone or with other abnormalities. The least adhered-to reporting elements were puncture site (91.9%), relevant clinical data (85.2%), and morphological evaluation by cell line (52.6%). Additionally, 27.4% of the reports were excluded due to poor sample quality. The most frequent diagnosis in dogs was hypoplasia (36.1%), while in cats, it was neoplasia (40.0%). Erythroid hyperplasia and neoplasms were more prevalent in males, whereas granulocytic hypoplasia was more common in females. Conclusions: BMA as a diagnostic tool in dogs and cats in Colombia is rare. A significant proportion of samples did not meet quality criteria, and there was low adherence to reporting guidelines.

The reorganization of brain structures after intracerebral hemorrhage (ICH) insult is crucial to functional outcome. Although the pattern of neuronal rewiring is well-documented after ischemic stroke, the study of brain plasticity after ICH has been focusing on the enhancement of dendritic complexity. Here we hypothesized that functional restoration after ICH involves brain reorganization which may be favorably modulated by stem cell transplantation. In this study, bone marrow stromal cells (BMSCs) were transplanted into the perilesional sites of collagenaseinduced ICH in adult rats one day after ICH injury. Forelimb functional recovery was monitored with modified limb placing and vibrissae-elicited forelimb placement tests. Anterograde and retrograde tracing were used to assess the reorganization of bilateral forelimb areas of the sensorimotor cortex. We found that in rats transplanted with BMSCs after ICH injury, axonal sprouting occurred in the contralateral caudal forelimb area of the cortex, and was significantly higher than in ICH rat models that received only the vehicle (P 0.01). The number of positive neurons in the ipsilateral rostral forelimb area of the cortex of the BMSC group was 1.5- to 4.5-fold greater than in the vehicle group (P 0.05). No difference was found between the BMSC and vehicle groups in hemispheric atrophy or labeled neurons in the ipsilateral caudal forelimb area (P

Innate nonself recognition must rely on common structures of invading microbes. In a differential display screen for up-regulated immune genes in the moth Trichoplusia ni we have found mechanisms for recognition of bacterial cell wall fragments. One bacteria-induced gene encodes a protein that, after expression in the baculovirus system, was shown to be a peptidoglycan recognition protein (PGRP). It binds strongly to Gram-positive bacteria. We have also cloned the corresponding cDNA from mouse and human and shown this gene to be expressed in a variety of organs, notably organs of the immune system-i.e., bone marrow and spleen. In addition, purified recombinant murine PGRP was shown to possess peptidoglycan affinity. From our results and the sequence homology, we conclude that PGRP is a ubiquitous protein involved in innate immunity, conserved from insects to humans

Macrophage-derived foam cells express apolipoprotein E (apoE) abundantly in atherosclerotic lesions. To examine the physiologic role of apoE secretion by the macrophage in atherogenesis, bone marrow transplantation was used to reconstitute C57BL/6 mice with macrophages that were either null or wild type for the apoE gene. After 13 weeks on an atherogenic diet, C57BL/6 mice reconstituted with apoE null marrow developed 10-fold more atherosclerosis than controls in the absence of significant differences in serum cholesterol levels or lipoprotein profiles. ApoE expression was absent in the macrophage-derived foam cells of C57BL/6 mice reconstituted with apoE null marrow. Thus, lack of apoE expression by the macrophage promotes foam cell formation. These data support a protective role for apoE expression by the macrophage in early atherogenesis.

Bone marrow-derived cells have been postulated as a source of multipotent mesenchymal stem cells (MSC). However, the whole fraction of MSC remains heterogeneous and the expansion of primitive subset of these cells is still not well established. Here, we optimized the protocol for propagating the low-adherent subfraction of MSC which results in long-term expansion of population characterized by CD45-CD14+CD34+ phenotype along with expression of common MSC markers. We established that the expanded MSC are capable of differentiating into endothelial cells highly expressing angiogenic markers and exhibiting functional properties of endothelium. Moreover, we found these cells to be multipotent and capable of giving rise into cells from neuronal lineages. Interestingly, the expanded MSC form characteristic cellular spheres in vitro indicating primitive features of these cells. In sum, we isolated the novel multipotent subpopulation of CD45-CD14+CD34+ bone marrow-derived cells that could be maintained in long-term culture without losing this potential.

To support and enhance the in vitro growth and activity of mesenchymal stem cells (MSCs), the cell culture medium may be supplemented with various proteins and factors to mimic the physiological environment in which the cells optimally proliferate and differentiate. In this study, the effects of mechanical factors on cellular metabolic responses were investigated experimentally using a bioreactor. The effects of various chemical factors, such as growth factors, cytokines, and hormones, were also investigated.

Porous calcium phosphates have osteoconductive properties. The aim of this study was to obtain synthetic calcium phosphate bone graft substitute. X-ray diffraction was employed to investigate the formation of the beta-tricalcium phosphate (β-TCP) phase. We evaluated the effects of bone marrow on the osteoconductivity and mechanical properties of synthetic bone graft (SG). SG cylinders loaded with bone marrow (SGBM) and SG alone were implanted into rabbits femoral condyle bone defects. Histological examinations revealed the resorption of the SG, trabecular bone with osteoblasts and osteoid substance around the implants, and colonization inside the porous β-TCP by newly formed bone. Histomorphometry conducted after three months revealed the osteoid surface to be higher in SGBM than SG (p less than 0.05). The compressive strengths of SG and SGBM were significantly higher than the anatomic control at all time periods. The elastic modulus of SBG and SGBM became weaker after implantation. The present results indicate that β-TCP is a good matrix for bone marrow, which contributes osteoinductive properties in an orthotopic. The composite biomaterial may be useful in reconstructive bone surgery.

Bone Marrow Pathology has been extensively revised to reflect the significant advances which have occurred in the application of cytogenetics and in particular, molecular genetics in the diagnosis, classification and understanding of haematological disorders.

Pycnogenol (procyanidin extracted from Pinus maritima) has been shown to be a potent free radical scavenger and an antioxidant phytochemical. The effects of pycnogenol on immune and haemopoietic dysfunction in senescence-accelerated mice (SAM), as a murine model of accelerated ageing, were determined. SAMP8, a strain of senile-prone mice, exhibit learning and memory deficits, immunodeficiency and dysfunction of the haemopoietic system. Oral feeding with pycnogenol for 2 months significantly improved their T- and B-cell function. Pycnogenol also augmented the proliferative capacity of haemopoietic progenitors of bone marrow in SAMP8. These data suggest that pycnogenol may be useful for either retardation or restoration of parameters associated with ageing.