Ovariectomy-associated changes in bone mineral density and bone marrow haematopoiesis in rats

The relationship between the bone mass loss and bone marrow haematopoiesis in osteoporosis remains obscure. We selected 3-month-old female Sprague–Dawley rats and randomly divided them into six groups. Three groups were ovariectomized (OVX), while the other three groups were sham operated (Sham). Four, 8 and 12 weeks after the surgical procedure, the rats were euthanized and sampled. The left femur was used for measurement of bone mineral density (BMD). The right femur distal metaphysic cancellous bone was processed for morphological evaluation. Our results showed that the femur BMD in the 4-week OVX group was not significantly decreased compared with that of the 4-week Sham group, but that the volume of adipose tissue in the bone marrow was markedly increased. The femur BMD in the 8-week OVX group was decreased significantly compared with that of the 8-week Sham group ( P   <   0.05). Meanwhile, the volume of haematopoietic tissue decreased and the volume of adipose tissue increased. The number of megakaryocytes was decreased ( P   <   0.05). Interestingly, the osteoclasts and mast cells were increased in number in the 8-week OVX group ( P   <   0.05). These changes became obvious in the 12-week OVX rats, in contrast to the Sham groups. The volume of trabecular bone and the number of osteoblasts in the 12-week OVX group decreased significantly. Increased reticulin fibres were observed only in the 12-week OVX group. Our studies demonstrated a reciprocal correlation between bone-forming osteoblasts and marrow adipose tissue and suggest that OVX rats may be valuable as an animal model to study hypohaemopoiesis.     

Epithelial changes following bone marrow transplantation: cytological atypia and epithelial endocrine cells

This report describes the histological and immunocytochemical findings in gastrointestinal biopsies and skin of a patient with chronic granulocytic leukaemia which progressed to blastic transformation, who was then treated with chemotherapy and total body irradiation followed by allogeneic bone marrow transplantation. The gut showed endocrine cells in the lamina propria and these had an immunophenotype similar to the glandular epithelium at the sites studied (stomach, duodenum and rectum), supporting the idea that the endocrine cells of the gut are more resistant to the effect of radiation, chemotherapy and graft-versus-host disease (GVHD) than are other cell types in the epithelium, and that lamina proprial endocrine cells are epithelially derived in this situation. Epidermis and gut epithelium also showed marked atypia due to the conditioning regimen and GVHD, and this case illustrates the possibility of misdiagnosis of carcinoma in this increasingly common situation. An additional, unusual feature of this case was the presence of a B-cell UCHL1 + ve lymphoma of the colon at autopsy, 122 days post-transplantation.     

Immunological reconstitution following bone marrow transplantation

Summary: The recipients of hematopoietic stem cell transplants are characterized by an immunodeficiency of varying severity and duration. Their immunoincompetence is due in part to: 1) a lack of sustained transfer of donor immunity, 2) a recapitulation of lymphoid ontogeny, 3) the effects of graft-versus-host disease and its therapy, and 4) a reduction in thymic function. Recipients can have delays in the production of naive T lymphocytes following transplantation which result in defects in the production of new antigen-specific T lymphocytes and an inability to produce antibodies, especially to carbohydrate antigens.     

Two-year follow-up of bone mineral density changes in the knee after meniscal allograft transplantation: Results of an explorative study

Background

The potential chondroprotective effect of meniscal allograft transplantation (MAT) is unclear. Subchondral bone mineral density (BMD) and subchondral bone remodeling play important roles in osteoarthritis development. Evaluation of subchondral BMD after MAT might give more insight into the potential chondroprotective effect. The purpose of this study was to determine early BMD changes in the knee after MAT.

Early reconstitution of haematopoiesis after allogeneic bone marrow transplantation: a prospective histopathological study of bone marrow biopsy specimens.

To study early haematopoietic reconstitution after bone marrow transplantation bone marrow biopsy specimens taken in the third week after transplantation were evaluated. Cellularity was highly variable; localisation of the various cell lineages and the ratios of myeloid cells to erythroid cells were abnormal. Clustering of cells of the same lineage in the same stage of maturation was prominent. The bone marrow stroma showed many anomalies, including increased fibre content, periodic acid Schiff positivity of fat cells, oedema, sinus ectasia and granulomas. A comparison of biopsy findings with clinical and laboratory data showed a correlation between the amount of erythroid cells and the day of appearance of reticulocytes, as well as the number of reticulocytes. Absence of clustering of haematopoietic cells in four of five patients was associated with either failure of engraftment or early leukaemic relapse. Variables such as infections and administration of possibly myelosuppressive drugs did not influence bone marrow biopsy findings.     

HSV excretion after bone marrow transplantation: a 4-year survey

BACKGROUND: Herpes simplex virus (HSV) oral excretions are common after bone marrow transplantation (BMT). OBJECTIVE: We report a 4-year systematic survey of HSV excretions in an adult population who underwent BMT (289 transplantations). STUDY DESIGN: Patients received either intravenous ACV treatment when mucositis occurred or systematic intravenous ACV prophylaxis from initiation of the BMT conditioning until the end of aplasia. All patients were followed up for HSV excretions. RESULTS: Twenty-eight patients (9.7%) excreted HSV. The occurrence of HSV excretions was similar in both allogeneic and autologous transplant patients. The incidence was significantly lower when ACV was systematically used after transplantation (2.5%) compared to when ACV was implemented for mucositis (12%). ACV-resistant HSV was detected in three patients who received allogeneic transplantation, representing 27% of allogeneic recipients excreting HSV. CONCLUSION: HSV infection prophylaxis with high dose of intravenous ACV resulted in a decreased incidence of HSV excretion. Nevertheless, the risk of emergence of ACV resistance, especially among allogeneic transplant patients, appears to be identical whatever the route and dose of ACV prophylaxis.     

A prospective study of diagnosis of Toxoplasma gondii infection after bone marrow transplantation

Active infection with Toxoplasma gondii in immunocompromised transplant recipients can lead to toxoplasmosis, which may have a rapid disease course and in some cases be fatal. It is of paramount importance to diagnose toxoplasmosis at an early stage, and to initiate specific treatment to improve the outcome. Polymerase chain reaction (PCR) is today the primary diagnostic tool to diagnose toxoplasmosis in immunocompromised patients. Timely diagnosis may, however, be difficult if toxoplasmosis is at first asymptomatic. To investigate the magnitude of toxoplasmosis after bone marrow transplantation (BMT), we conducted a screening study by PCR where 21 autologous and 12 allogeneic BMT recipients were included. Peripheral blood samples were taken one week prior to BMT; thereafter, blood samples were drawn weekly for the first 6 months, and monthly up to one year after BMT. The samples were analyzed by conventional PCR and real-time PCR. T. gondii DNA was detected in peripheral blood from one patient 5 days post allogeneic BMT. There were no clinical signs of toxoplasmosis. Medical records were reviewed and showed a previously undiagnosed eye infection in another allogeneic BMT recipient. These two patients were seropositive for T. gondii. We concluded that monitoring for T. gondii DNA in peripheral blood samples using PCR might be a valuable method for identifying toxoplasma-seropositive stem cell transplant recipients.     

Functional hyposplenism following allogeneic bone marrow transplantation.

AIMS--To investigate the incidence of functional hyposplenism in a group of patients who had undergone allogeneic bone marrow transplantation (BMT). METHODS--Splenic function was assessed by counting the number of gluteraldehyde fixed red blood cells containing pits or indentations as examined by interference phase microscopy. Normal values are < 2% whereas splenectomy patients have values of 25 to 40%. RESULTS--Twenty eight BMT recipients (17 men, 11 women) were studied at varying periods post-transplant and the results compared with 20 healthy volunteers and 10 patients who had undergone splenectomy or had splenic atrophy because of haematological conditions. Of the 28 BMT recipients, one had undergone a prior splenectomy; of the remaining 27 patients, four (15%) had evidence of functional hyposplenism with between 5.0 and 34.0% pitted cells. Of these four patients, one had active extensive chronic graft versus host disease (GvHD) which has been previously reported to be associated with functional hyposplenism following transplantation. Only one of the four patients had peripheral blood red cell changes typical of hyposplenism. CONCLUSION--These results confirm that extensive chronic GvHD is associated with hyposplenism. Intermediate degrees of functional hyposplenism may also occur following BMT in the absence of chronic GvHD and in the absence of haematological features of hyposplenism on routine blood films. This may be of significance in mediating the susceptibility to infection with encapsulating bacteria seen following allogeneic BMT.     

骨髓同种异体干细胞移植后淋巴组织增殖性疾病

1.病例简介:患者男,34岁。无明显诱因出现活动后乏力、气短,自觉头晕、头痛9个月入院。体检无明显异常。血常规示红细胞及白细胞减少,分片偶见原始细胞。骨髓穿刺示原始+幼稚淋巴细胞占59%。流式细胞学免疫分型CD33、CD7、CD11b、CD19、CD5、CD2、CD3阳性。染色体未见异常。临床诊断为急性淋巴细胞性白血病,双表型。于确诊后7个月进行骨髓同种异体干细胞移植。移植后给予环孢酰胺免疫抑制剂治疗,病情平稳。于移植后第55天检查发现患者右颈后可触及肿大淋巴结2枚,大小均约1·5cm×1·0cm×1·0cm。临床考虑:(1)白血病髓外复发;(2)病毒…     

Periprosthetic bone mineral density changes after unicondylar knee arthroplasty

BackgroundUnicompartmental knee arthroplasty (UKA) has received renewed interest in the last decade. UKA involves minor injury to soft tissues, limited removal of bone and delicate preservation of knee anatomy and geometry. In theory, UKA provides an opportunity to restore post-surgical knee kinematics to near normal.HypothesisUKA leaves patellofemoral joint free to meet high mechanical forces with no stress-shielding and therefore might preserve bone mineral density (BMD).Patients and methodsWe studied 21 patients with osteoarthritis(OA), who had received medial compartment UKA at Kuopio University Hospital between October 1997 and September 2000. BMD was measured by dual-energy X-ray absorptiometry (DEXA), at baseline (within a week after surgery) and at intervals until 7 years.ResultsDEXA results were reproducible. The highest rate of periprosthetic bone loss occurred during the first 3 months after UKA. The average loss in BMD was 4.4% (p = 0.039) in the femoral diaphysis and it ranged from 11.2% (p < 0.001) to 11.9% (p = 0.002) in the distal femoral metaphysis; however, BMD changes in these regions, from 2 years to 7 years, were nonsignificant. At the 1-year follow-up, the BMD of the medial tibial metaphysis had increased by 8.9% (p = 0.02), whereas those in the lateral tibial metaphysial (–2.4%) and diaphysial regions (–2.0%) did not change significantly.InterpretationsUKA did not preserve periprosthetic BMD in the distal femoral metaphysis, whereas BMD changes in the tibial metaphysis were minor, consistent with a mechanical balance between the medial and lateral tibial compartments.Level of Evidence 2bProspective case control study.     

Physical activity and 5-year changes in physical performance tests and bone mineral density in postmenopausal women: the Yokogoshi Study

Objective

The effect of physical activity on musculoskeletal health in older adults is not completely understood. The aim of this study was to determine the relationship between physical activity and 5-year changes in physical performance tests and bone mineral density (BMD) in postmenopausal women.

Study design

The design was a 5-year cohort study.

Main outcome measures

Subjects were 507 women (55-74 years old) living in a rural community in Japan. Physical activity assessed included housework, farm work, and moderate leisure-time physical activity within the previous week. Measurements at baseline included handgrip strength, walking time (timed “Up & Go” test) and BMD of the femoral neck and vertebrae. Five-year changes in these measures (outcome variables) were compared among groups with different levels of physical activity by analysis of covariance.

Results

Women who did not do housework performed worse in changes in handgrip strength (difference = 2.22 kg, P = 0.0201) and worse in changes in the walking time (difference = 0.54 s, P = 0.0072) than those who did housework alone. Women who spent at least 9 h per week (median = 24) doing farm work performed better in changes in handgrip strength (difference = 0.28 kg, P = 0.0334), but worse in changes in the walking time (difference = 0.66 s, P < 0.0001) than those who did not do farm work. However, leisure-time activity was not associated with changes in any outcome variable, and none of the physical activities predicted BMD changes.

Conclusions

Engaging in housework and farm work are determinants of physical function in postmenopausal women, which may help them maintain independence in daily living.     

Fungal encephalitis following bone marrow transplantation: clinical findings and prognosis

Background: Central nervous system fungal infections (FI) are important complications and a cause of mortality in patients who receive hematopoietic stem cell transplantation (HSCT). Aims: To study the clinical aspects of fungal encephalitis (FE). Settings and Design: The study was carried out at the HSCT Center of the Hospital de Clnunicas, Federal University of Paranalpha, Curitiba, Brazil. Materials and Methods: Clinical records and autopsy reports from patients submitted to HSCT with a diagnosis of FE. Results: Twelve patients were diagnosed with FE presenting with lowered level of consciousness, hemiparesis and seizures. We were able to identify two subgroups regarding susceptibility to FE: (1) patients with early onset FI and severe leucopoenia, and (2) patients with later onset FI with graft-versus-host disease using immunosuppressive drugs. Eleven of the patients died directly due to the neurological complication, all had post-mortem confirmation of the diagnosis of FI. Conclusions: These clinical, paraclinical and temporal patterns may provide the opportunity for earlier diagnosis and interventions.     

自体骨髓干细胞移植治疗血栓闭塞性脉管炎：5年随访

背景：慢性缺血性疾病的长期疗效评估较短期疗效评估更为重要,关系患者远期生活质量及长期生存率。 目的：分析自体骨髓干细胞移植治疗血栓闭塞性脉管炎的5年随访结果。 方法：收集新疆医科大学第一附属医院血管甲状腺外科自2007年8月至2010年1月行自体骨髓干细胞移植的血栓闭塞性脉管炎患者43例。移植后1,2,3,4,5年电话定期随访疼痛、冷感、间歇性跛行距离,并观察患肢溃疡的变化情况。移植后1年复查患肢静脉血氧分压和血氧饱和度。 结果与结论：有完整随访资料的血栓闭塞性脉管炎患者38例进入结果分析。38例患者的疼痛、冷感、间歇性跛行情况较移植前明显好转,差异有显著性意义(Z值分别为-4.277、-5.086、-3.574,P < 0.001)。移植后1-5年间相比,患者的疼痛、冷感情况差异无显著性意义(P > 0.05),间歇性跛行距离逐渐增加,差异有显著性意义(Z=43.898,P < 0.001)。患肢静脉血氧分压和血氧饱和度移植前与移植后1年对比差异有显著性意义(t值分别为36.790、43.964,P值分别为0.040、0.037)。以上结果表明自体骨髓干细胞移植治疗血栓闭塞性脉管长期效果稳定。  中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

FOXP3 expression following bone marrow transplantation for IPEX syndrome after reduced-intensity conditioning

The objective of this study is to determine if immune reconstitution of FOXP3+ T regulatory cells correlates with clinical improvement of IPEX syndrome following allogeneic hematopoietic stem cell transplant. An 8-months-old male infant with a mutation in the polyadenylation site of FOXP3 gene, absence of FOXP3 protein expression and clinical manifestations of IPEX syndrome, including eczema, colitis, failure to thrive, TPN requirement, and elevated serum IgE, underwent matched unrelated hematopoietic stem cell transplant. After reduced-intensity conditioning with alemtuzumab followed by fludarabine and melphalan the patient’s neutrophils engrafted day +15 and platelets day +29. Patient was a full donor chimera day +28 and +60. Intracellular FOXP3 protein expression in CD4+ T cells was absent pre-HSCT. After transplantation, percentage CD4+ T cells expressing FOXP3+CD25 bright phenotype quickly increased from 4.5 (day +29) to 23% (day +90) and continued in this trend. Foxp3 mRNA expression confirmed flow cytometry data. Serum IgE levels decreased from 5,000 IU/ml pre-transplant to 6 IU/ml on day +90, eczema resolved, and secretory diarrhea and feeding intolerance improved. T regulatory cell reconstitution is evident soon after HSCT following reduced-intensity conditioning correlating with development of full donor chimerism. Increased FOXP3 expression correlates with correction of clinical and laboratory manifestations of IPEX syndrome providing direct evidence that HSCT is a curative procedure for this disorder.     

Psychosocial predictors of immune response following bone marrow transplantation

This study analyzed the relationship between some psychosocial variables (depression, anxiety, stress, coping strategies, social support, optimism, rationality, and need for harmony) and clinical parameters indicative of immunological response after bone marrow transplantation (BMT; day of engraftment, number of infections and hemoglobin level) while controlling for demographic variables (age, educative level, civil state, and time from cancer diagnosis). Thirty-one post BMT hematological cancer patients were evaluated. Results show that higher educative levels are associated to lower number of infections, while age is associated with a delay in the time of engraftment; coping strategies, specially redefinition of the situation, relaxation, stoicism and passivity, are positively associated with the three clinical indices; depression is positively associated to number of infections during the hospitalization period; and rationality is associated with lower hemoglobin levels. These results suggest that psychosocial variables, especially coping strategies, play an important role in determining the immunological response after BMT.     

Histopathological changes in the liver after allogeneic bone marrow transplantation

Postmortem and surgical specimens of liver from 20 patients who had undergone allogeneic bone marrow transplantation for a variety of disorders were examined. The lesions fell into five major categories: bile duct atypia often associated with portal tract fibrosis (8 cases), veno-occlusive disease (2 cases), small foci of non-zonal hepatocyte necrosis (3 cases), opportunistic infections (3 cases), and a miscellaneous group of non-specific abnormalities. Our findings, in conjunction with those in experimental animals, point strongly to the bile duct lesion being a specific manifestation of graft versus host disease (GvHD). Veno-occlusive disease has also been reported recently as a possible manifestation of a graft versus host reaction and, although both our patients with this lesion had evidence of GvHD in the skin and gastrointestinal tract, both had also received irradiation and 6-thioguanine, and these may have been responsible. The foci of hepatocyte necrosis could not be attributed to GvHD with any confidence as the lesion was of only minor severity, infrequent, highly non-specific in appearance and, furthermore, did not correlate well with the presence of bile duct lesions. The absence of specific clinical and biochemical findings in human hepatic GvHD stresses the need for biopsy to make a firm diagnosis. However, the patchy distribution of the bile duct lesion and its absence from the needle biopsies examined in this study suggest possible sampling problems, and further study is necessary to assess its value.