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PubMed2002

Comparison between granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in the mobilization of peripheral blood stem cells.

Peripheral blood stem cells (PBSC) have become the preferred source of stem cells for autologous transplantation because of the technical advantage and the shorter time to engraftment. Mobilization of CD34+ into the peripheral blood can be achieved by the administration of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), or both, either alone or in combination with chemotherapy. G-CSF and GM-CSF differ somewhat in the number and composition of PBSCs and effector cells mobilized to the peripheral blood. The purpose of this review is to give a recent update on the type and immunologic properties of CD34+ cells and CD34+ cell subsets mobilized by G-CSF or GM-CSF with emphasis on (1) relative efficacy of CD34+ cell mobilization; (2) relative toxicities of G-CSF and GM-CSF as mobilizing agents; (3) mobilization of dendritic cells and their subsets; (4) delineation of the role of adhesion molecules, CXC receptor 4, and stromal cell-derived factor-1 signaling pathway in the release of CD34+ cell to the peripheral blood after treatment with G-CSF or GM-CSF.

Animals↗

PubMed2003

Comparison of clients of a mobile health van and a traditional STD clinic.

The objective of this study was to determine if there were any demographic, behavioral, and clinical differences between clients seen aboard a mobile sexually transmitted disease (STD)/HIV clinic compared with those seen in a traditional municipal STD/HIV health clinic for receipt of STD/HIV services. Clients seen in the two different settings were interviewed about demographic characteristics, reasons for their visit, STD history, their HIV/STD risk factors, and the risk factors of their sex partners. Clients in both settings were also offered testing for syphilis, gonorrhea, chlamydia, and HIV. Results suggested that clients seen at the mobile clinic were older, more likely to be injecting drug users themselves and/or to have sex partners who were, or had engaged in prostitution for money or drugs. Over half (54.4%) of the mobile clinic clients sought testing for HIV, and they were far less likely to be seeking care for symptoms of an STD. In contrast, only 7.1% of municipal clinic clients indicated HIV testing as the reason for their visit, whereas nearly two thirds (64.5%) reported symptoms of disease. Two percent of municipal clinic clients and 5.4% of mobile clinic clients had a positive HIV test ( p<.001), and 17.8% of STD clinic clients and 5.6% of mobile van clients had a positive gonorrhea and/or test ( p<.001). These data suggest that a mobile STD/HIV clinic may be an effective strategy to reach individuals at high risk for HIV who are not being served by traditional municipal STD/HIV health clinics.

Adult↗

PubMed2006

Lower extremity physical performance and use of compensatory strategies for mobility.

OBJECTIVES: To compare measured lower extremity physical performance in the clinic with the methods used to carry out mobility tasks at home and to identify key factors influencing day-to-day task performance. DESIGN: Cross-sectional analysis of the Women's Health and Aging Study I. SETTING: Community-dwelling female residents of Baltimore, Maryland. PARTICIPANTS: One thousand two cognitively intact women aged 65 and older with moderate to severe physical limitations. MEASUREMENTS: Compensatory strategies reportedly used for mobility in the home, distinguishing between use of no compensatory strategies, behavioral changes only, durable medical equipment (DME) with or without behavioral change, and human help; measured lower extremity (LE) physical performance (gait speed, timed chair stands, balance). RESULTS: There was a statistically significant difference in LE physical performance between women using the four types of compensatory strategy (P < .001). Women who used DME for mobility in the home had worse performance than those using human help who in turn had worse performance than those with behavioral changes only; women reporting no compensatory strategies for in-home mobility performed best. Sequential multivariate logistic regressions identified several factors other than LE physical performance that were associated with use of specific compensatory strategies. Medical conditions, education, and environmental barriers influenced whether compensatory strategies were used at all, whereas income, contact with health providers, and availability of help in the home influenced the type of compensatory strategy. CONCLUSION: Physical abilities are an important factor influencing use of compensatory strategies for mobility, but several other factors also influence the ways that women adapt to mobility limitations.

Activities of Daily Living↗

PubMed2006

Metabolic syndrome predicts mobility decline in a community-based sample of older adults.

OBJECTIVES: To determine whether metabolic syndrome is an independent predictor of decline in mobility in an elderly community sample. DESIGN: Biracial community-based prospective cohort study. SETTING: Urban and rural areas of central North Carolina. PARTICIPANTS: One thousand two hundred twenty-nine older African Americans and whites, mean age 77.0, who were participants in the Duke Established Populations for Epidemiologic Studies of the Elderly. MEASUREMENTS: Sociodemographic data and data on mobility (a subset of items from the Rosow-Breslau scale), depression (Center for Epidemiological Studies Depression Scale), self-report of medical conditions, body mass index, cognitive function (Short Portable Mental Status Questionnaire), blood pressure, height, and waist circumference. High-density lipoprotein cholesterol, triglycerides, and blood glucose were available from blood samples. Metabolic syndrome was calculated for subjects with complete data. RESULTS: Twenty-nine percent of the sample met criteria for metabolic syndrome. In bivariate analyses, age, sex, race, education, cognitive impairment, depression, impairment in mobility, history of stroke and heart disease, and metabolic syndrome at baseline were associated with a decline in mobility 4 years later. Regression analysis controlling for the above variables demonstrated that metabolic syndrome persisted as an independent and highly significant predictor of decline in mobility. CONCLUSION: These findings suggest that metabolic syndrome may be a distinct risk factor for mobility decline in community-dwelling older people.

Activities of Daily Living↗

PubMed1979

The effect of splinting on tooth mobility. (2) After osseous surgery.

The purpose of this study was to determine if fixed splinting of teeth with intraoral wire and acrylic splints had advantages with respect to tooth mobility, bone level and attachment level over unsplinted teeth following osseous surgery. Ten patients were chosen who exhibited bilaterally similar chronic destructive periodontitis and mobile teeth. One maxillary sextant was splinted, while the other was unsplinted. Both sextants functioned against an unsplinted mandibular arch. Following initial therapy, osseous surgery was performed in both maxillary sextants on the same day. Tooth mobility data was collected 1 week before and at 3, 6, 12, and 24 weeks following surgery. Levels of gingival attachment and bone were recorded before and 24 weeks after surgery. Splints were removed before measurements, then replaced, and the occlusion refined. Prophylaxes and oral hygiene instruction were repeated every 3 weeks throughout the study. For all categories of teeth and mobility examined, tooth mobility increased initially after surgery and subsequently decreased by 24 weeks to about presurgical values. The splinted and unsplinted segments reacted similarly throughout the study; splinting did not significantly reduce the mobility of individual teeth. Pre- and postsurgical bone and gingival attachment levels were also similar for the splinted and unsplinted segments.

Adult↗

PubMed1980

Clinical standardization of horizontal tooth mobility.

The clinical measurement of horizontal tooth mobility is discussed on the background of the current theories regarding the pathogenesis of periodontal disease. The common indices which have been designed to measure horizontal tooth mobility are discussed and critiqued. These indices are not sensitive in that they do not discriminate well between small increments in mobility. In addition, many of the indices cannot be utilized for individual teeth on a longitudinally reproducible basis. The preliminary testing of an in vitro model with mobile teeth which was designed to aid the clinician in assessing tooth mobility is described. Results indicate that the clinician may be capable of discriminating between mobilities that are in the 0.1 mm range, with the aid of the model.

Dental Instruments↗

PubMed1980

Interrelationship of inflammation and tooth mobility (trauma) in pathogenesis of periodontal disease.

A series of studies has investigated interactions between periodontal trauma and marginal periodontitis in relation to the initiation, progression and treatment of periodontal disease. Lesions of trauma in the periodontal ligament consequent to either single or jiggling displacing forces result in morphologic alterations in the ligament and alveolar bone. These changes do not initiate the loss of connective tissue attachment characteristic of marginal periodontitis. Studies conducted in squirrel monkeys and beagle dogs in which jiggling forces have been produced subjacent to an established marginal periodontitis reported increased loss of alveolar bone, but the accelerated loss of attachment which occurred in the dog model did not occur in the monkey model. To clarify the relative importance of inflammation and tooth mobility in the treatment of advanced periodontal disease, periodontal response was evaluated after removing traumatic and/or inflammatory components. Elimination of trauma in the presence of existing marginal inflammation did not reduce tooth mobility or increase bone volume. Osseous regeneration and decreased tooth mobility occurred after resolving both components, however, similar findings occurred after resolving inflammation in the presence of continued tooth mobility. Resolution of marginal inflammation is of prime importance in the management of periodontal disease. After resolution of inflammation, bone regeneration may occur around mobile teeth and, furthermore, any residual tooth mobility does not result in increased loss of connective tissue attachment.

Animals↗

PubMed1980

Tooth mobility and periodontal therapy.

Data collected as part of an 8-year longitudinal study on periodontal therapy involving 82 patients and 1974 teeth were analyzed to determine if tooth mobility influenced the result of treatment. For each patient, pocket depth, attachment level and tooth mobility were scored clinically at the initial appointment, and once a year for 8 years following periodontal therapy. The treatment consisted of scaling, oral hygiene instruction, occlusal adjustment, periodontal surgery (curettage, modified Widman or pocket elimination), followed by recall prophylaxes every 3 months. Tooth mobility data on a scale of 0--3 were related to changes in attachment levels for three grades of severity of periodontal disease, based on initial pocket depth (1--3 mm, 4--6 mm, and 7 + mm). Mean patient attachment changes were calculated from teeth in the same severity category for each patient. The data were analyzed by one-way analysis of variance and Scheffe's multiple comparison procedure to test the hypothesis of equal effects of tooth mobility on the results of the treatment for the three severity groups over 8 years. The results indicate that there is a statistically significant relationship between original tooth mobility and the change in level of attachment following treatment. Pockets of clinically mobile teeth do not respond as well to periodontal treatment as do those of firm teeth exhibiting the same initial disease severity.

Humans↗

PubMed1996

Inequalities in self rated health in the 1958 birth cohort: lifetime social circumstances or social mobility?

OBJECTIVE: To investigate explanations for social inequalities in health with respect to health related social mobility and cumulative socioeconomic circumstances over the first three decades of life. DESIGN: Longitudinal follow up. SETTING: Great Britain. SUBJECTS: Data from the 1958 birth cohort study (all children born in England, Wales, and Scotland during 3-9 March 1958) were used, from the original birth survey and from sweeps at 16, 23, and 33 years. MAIN OUTCOME MEASURES: Subjects' own ratings of their health; social differences in self rated health at age 33. RESULTS: Social mobility varied by health status, with those reporting poor health at age 23 having higher odds of downward mobility than of staying in same social class. Men with poor health were also less likely to be upwardly mobile. Prevalence of poor health at age 33 increased with decreasing social class: from 8.5% in classes I and II to 17.7% in classes IV and V among men, and from 9.4% to 18.8% among women. These social differences remained significant after adjustment for effects of social mobility. Health inequalities attenuated when adjusted for social class at birth, at age 16, or at 23 or for self rated health at age 23. When adjusted for all these variables simultaneously, social differences in self rated health at age 33 were substantially reduced and no longer significant. CONCLUSIONS: Lifetime socioeconomic circumstances accounted for inequalities in self reported health at age 33, while social mobility did not have a major effect on health inequalities.

Adolescent↗

PubMed1991

Relation between job mobility during working life and health state after retirement: a cross sectional study of 627 subjects living in the Paris area.

The relation between job mobility during working life and health state after retirement was studied in a random sample of 627 retired men and women living in the Paris area who were beneficiaries of an interprofessional supplementary pension fund. State of health was evaluated by the number of health impairments that these subjects reported at the time of interview. Job mobility was defined by a dichotomic variable based on the number of different companies and branches of economic activity in which the subjects had worked. This information was obtained from the individual records supplied by the pension fund. For both sexes, a significant relation was found between the number of health impairments and job mobility: for men, the mean number of impairments was 1.7 in the high mobility group and 1.3 in the low mobility group, and for women these numbers were respectively 2.1 and 1.7. This finding seemed independent of the effects of selection and of the effects of factors such as age at the time of interview, age at retirement, previous diseases, past work accidents, and previous occupational exposures. These results suggest that a high job mobility during working life might be a risk factor for health after retirement.

Aged↗

PubMed1995

U.S. screening mammography services with mobile units: results from the National Survey of Mammography Facilities.

PURPOSE: To investigate elements of mobile facilities for mammography in the United States. MATERIALS AND METHODS: The prevalence and performance of mobile facilities for mammography in the United States were studied with regard to cost, price, quality assurance, and access. Data were acquired from the National Cancer Institute's National Survey of Mammography Facilities, conducted in 1992. RESULTS: Of the 1,057 facilities surveyed, 2.4% were identified as mobile and accounted for 3% of mammography examinations performed. All mobile facilities reported accreditation by the American College of Radiology, and 92% were in Statistically Metropolitan Areas. Most were affiliated with community hospitals or private radiology practice and were more likely to be associated with lower fees, convenient operating hours, batch interpretation, and computerized reporting than were their stationary counterparts. CONCLUSION: Mobile mammography facilities compare favorably with stationary facilities. The use of these mobile units in the United States, however, has been limited.

Accreditation↗

PubMed2004

Characterization of hematopoietic progenitor mobilization in protease-deficient mice.

Recent evidence suggests that protease release by neutrophils in the bone marrow may contribute to hematopoietic progenitor cell (HPC) mobilization. Matrix metalloproteinase-9 (MMP-9), neutrophil elastase (NE), and cathepsin G (CG) accumulate in the bone marrow during granulocyte colony-stimulating factor (G-CSF) treatment, where they are thought to degrade key substrates including vascular cell adhesion molecule-1 (VCAM-1) and CXCL12. To test this hypothesis, HPC mobilization was characterized in transgenic mice deficient in one or more hematopoietic proteases. Surprisingly, HPC mobilization by G-CSF was normal in MMP-9-deficient mice, NE x CG-deficient mice, or mice lacking dipeptidyl peptidase I, an enzyme required for the functional activation of many hematopoietic serine proteases. Moreover, combined inhibition of neutrophil serine proteases and metalloproteinases had no significant effect on HPC mobilization. VCAM-1 expression on bone marrow stromal cells decreased during G-CSF treatment of wild-type mice but not NE x CG-deficient mice, indicating that VCAM-1 cleavage is not required for efficient HPC mobilization. G-CSF induced a significant decrease in CXCL12 alpha protein expression in the bone marrow of Ne x CG-deficient mice, indicating that these proteases are not required to down-regulate CXCL12 expression. Collectively, these data suggest a complex model in which both protease-dependent and -independent pathways may contribute to HPC mobilization.

Animals↗

PubMed2006

Increased hematopoietic stem cell mobilization in aged mice.

Hematopoietic stem and progenitor cells (HSPCs) are located in the bone marrow in close association with a highly organized 3-dimensional structure formed by stroma cells, referred to as the niche. Mobilization of HSPCs from bone marrow to peripheral blood in response to granulocyte colony-stimulating factor (G-CSF) requires de-adhesion of HSPCs from the niche. The influence of aging of HSPCs on cell-stroma interactions has not been determined in detail. Using a mouse model of G-CSF-induced mobilization, we demonstrated that the ability to mobilize hematopoietic stem cells is approximately 5-fold greater in aged mice. Competitive mobilization experiments confirmed that enhanced mobilization ability was intrinsic to the stem cell. Enhanced mobilization efficiency of primitive hematopoietic cells from aged mice correlated with reduced adhesion of hematopoietic progenitor cells to stroma and with elevated levels of GTP-bound Cdc42. These results might indicate that stroma-stem cell interactions are dynamic over a lifetime and result in physiologically relevant changes in the biology of primitive hematopoietic cells with age.

Aging↗

PubMed2006

Angiogenic cells can be rapidly mobilized and efficiently harvested from the blood following treatment with AMD3100.

Circulating endothelial progenitor cells (EPCs) are thought to contribute to angiogenesis following vascular injury, stimulating interest in their ability to mediate therapeutic angiogenesis. However, the number of EPCs in the blood is low, limiting endogenous repair, and a method to rapidly mobilize EPCs has not been reported. In this study, healthy donors were mobilized sequentially with the CXCR4 antagonist, AMD3100, and G-CSF. The number of EPCs and circulating angiogenic cells (CACs) in the blood and pheresis product was determined and the angiogenic capacity of each cell population assessed. Compared with baseline, treatment with AMD3100 or G-CSF increased the number of blood CACs 10.0-fold +/- 4.4-fold and 8.8-fold +/- 3.7-fold, respectively. The number of EPCs in the blood increased 10.2-fold +/- 3.3-fold and 21.8-fold +/- 5.4-fold, respectively. On a percell basis, CACs harvested from G-CSF-mobilized blood displayed increased in vivo angiogenic potential compared with AMD3100-mobilized CACs. Mobilized EPCs displayed a greater proliferative capacity than EPCs isolated from baseline blood. Both CACs and EPCs were efficiently harvested by leukapheresis. Cryopreserved CACs but not EPCs retained functional activity after thawing. These data show that AMD3100 is a potent and rapid mobilizer of angiogenic cells and demonstrate the feasibility of obtaining and storing large numbers of angiogenic cells by leukapheresis.

Animals↗

PubMed2002

Mobilization, collection, and processing of peripheral blood stem cells in individuals with sickle cell trait.

Mobilized peripheral blood is increasingly used as the source of hematopoietic stem cells for allogeneic transplantation, currently the only curative approach for sickle cell anemia. However, the safety and feasibility of stem cell mobilization in individuals with sickle cell trait (SCT) has not been documented. This study is a prospective controlled trial to evaluate the safety and feasibility of peripheral blood stem cell (PBSC) mobilization in 8 SCT subjects and 8 control subjects matched for age and race. Mobilization with filgrastim 10 microg/kg subcutaneous daily for 5 days was followed by 12-L apheresis on the fifth day. Filgrastim administration was accompanied by similar symptoms in all subjects; no untoward adverse events occurred in either group, including sickle cell crises. CD34+ cell mobilization response was not significantly different between SCT and control subjects. Median CD34+ cell content was also similar in PBSCs collected from SCT versus control subjects, 6.8 versus 3.9 x 10(6) CD34+ cells/70 kg, P =.165. Red cell depletion from SCT products was not possible by using hydroxyethyl starch sedimentation but was achievable with ammonium chloride lysis. There was no evidence of gelling of SCT products after thaw, and no difference in cell recovery was seen among red cell-depleted versus nondepleted products. Cryopreservation in 5% dimethyl sulfoxide/6% pentastarch was associated with superior cell recovery (both SCT and control subjects) compared with 10% dimethyl sulfoxide (P =.001). The study concluded that filgrastim mobilization, large volume apheresis, processing, and cryopreservation appears to be safe in donors with SCT, allowing PBSC use for transplantation in patients with sickle cell anemia.

Adult↗

PubMed2005

New strategies for mobilization of hematopoietic stem cells.

A significant number of tumor patients fail peripheral blood progenitor cell (PBPC) mobilization and thus cannot receive potentially curative high-dose chemotherapy with subsequently required PBPC transplantation. New insights into the physiology of mobilization have revealed the pivotal role of the CXCR4/stromal derived factor-1alpha receptor-ligand interaction for stem cell retention in the bone marrow. New CXCR4 antagonists such as AMD3100 are currently in clinical studies. They act synergistically with the established mobilizing agent granulocyte colony-stimulating factor (G-CSF); thus, patients can collect more PBPCs in fewer apheresis sessions, and others that previously failed can now successfully collect sufficient PBPCs for transplantation. Experimental and clinical data suggest that the quality of AMD3100-mobilized PBPC may even be superior to PBPCs mobilized following standard therapy. CXCR4 antagonists are the most exciting development in the field of PBPC mobilization for over a decade. Additionally, new analogs of G-CSF are being introduced with favorable pharmacologic features.

Granulocyte Colony-Stimulating Factor↗

PubMed2000

CD44v10 in hematopoiesis and stem cell mobilization.

Transplantation of hematopoietic progenitor cells provides in many instances of malignant tumors an ultimate chance of curative therapy, whereby the transfer of peripheral blood stem cells (PBSC) may even be advantageous as compared to bone marrow cells. Yet, the transfer of PBSC requires mobilization of stem cells into the periphery, which is mostly achieved via hematopoietic growth factors like G-CSF. Although G-CSF has been found to efficiently mobilize stem cells in most instances, some patients do not or insufficiently respond to G-CSF treatment In addition, G-CSF treatment may by accompanied by maturation of the most primitive progenitors and this may have an impact on stem cell homing and recovery of hemopoiesis. Therefore, additional approaches for stem cell mobilization have been searched for, in particular mobilization via a blockade of an adhesion molecule expressed by CD34-positive cells, like VLA-4 (CD49d) and the hematopoietic isoform of CD44 (CD44s). We recently described that in the mouse one of the CD44 variant isoforms, CD44v10, is expressed on a subpopulation of bone marrow cells, whereas a CD44v10 receptor-globulin only binds to stromal elements. These features appeared promising for anti-CD44v10 as a means of stem cell mobilization. Indeed, treatment with anti-CD44v10 revealed promising results concerning the recovery of multilineage colony forming units in the spleen and the peripheral blood. We here summarize features of expression and function of CD44 in hematopoiesis an provide further evidence for anti-CD44v10 as a means to mobilize hematopoietic progenitor cells.

Animals↗

PubMed2001

Il-17 mobilizes peripheral blood stem cells with short- and long-term repopulating ability in mice.

Autologous and allogeneic bone marrow transplantations have evolved as important cancer therapy modalities. For both indications, peripheral blood has been shown to have distinct advantages over bone marrow as the stem cell source. Cytokine combinations for mobilization have enhanced stem cell yield and accelerated engraftment. However, novel mobilizing agents and strategies are needed to further improve clinical outcomes. Within the donor graft, the dynamic equilibrium between T cells and stem cells critically influences engraftment and transplantation results. IL-17 is a cytokine produced almost exclusively from activated T cells. IL-17 was expressed in vivo with adenovirus technology. Here, proof-of-principle studies demonstrate that IL-17 effectively mobilizes hemopoietic precursor cells (CFU-granulocyte-erythrocyte-macrophage-monocyte, CFU-high proliferative potential) and primitive hemopoietic stem cells (Lin(-/low)c-kit(+)Sca1(+)). Moreover, mouse IL-17 adenovirus-mobilized peripheral blood stem cells rescued lethally irradiated mice. Bone marrow was found to be 45-75% of donor origin at 1 year. In secondary recipients, donor-derived bone marrow cells ranged from 45 to 95%. These data show that IL-17 mobilizes stem cells in mice with short- and long-term reconstituting capacity. Additional comparative studies are needed as well as studies in tumor models to refine distinct potential clinical applications for IL-17-mobilized peripheral blood stem cells.

Animals↗