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Second attempts at mobilization of peripheral blood stem cells in patients with initial low CD34+ cell yields.

The purpose of this study was to determine the effectiveness of second mobilization strategies in patients who yielded < 2.5 x 10(6) CD34+ PBSC/kg after initial mobilization. Repeat mobilization attempts were made with chemotherapy and G-CSF (n = 61) or G-CSF alone (n = 58) in patients who failed initial mobilization with chemotherapy and G-CSF (n = 92) or G-CSF alone (n = 27). A median of 0.27 x 10(6) CD34+ cells/kg per apheresis was collected after the second mobilization, compared with 0.16 with initial harvests (p = 0.0001). Forty-eight percent achieved a target CD34+ cell dose > or = 2.5 x 10(6)/kg when harvests from the first and second mobilizations were combined. Fifteen of 17 patients (88%) with > or = 1.5 x 10(6) CD34+ cells/kg harvested after first mobilization had > or = 2.5 x 10(6) CD34+ cells/kg collected when first and second harvests were combined, as compared with 42 of 102 (41%) achieving < 1.5 x 10(6) CD34+ cells/kg with first PBSC harvests (p = 0.0001). Second mobilizations with chemotherapy and G-CSF or G-CSF alone resulted in similar CD34+ cell yields. Toxicities of second mobilizations were comparable with those of first mobilizations. Seventy-nine patients (66%) received high-dose chemotherapy with PBSC support, with recovery of neutrophils and platelets in a median of 11 and 15 days, respectively. Transplant-related mortality was 4%, and event-free survival at 2 years was 0.34. It was concluded that second mobilization attempts in patients who fail to achieve > or = 2.5 x 10(6) CD34+ cells/kg on initial mobilization were successful in 48% of patients. G-CSF alone was as effective as chemotherapy plus G-CSF in mobilizing CD34+ cells and was associated with less morbidity.

Adult↗

The role of exo-(1-->4)-beta-galactanase in the mobilization of polysaccharides from the cotyledon cell walls of Lupinus angustifolius following germination.

BACKGROUND AND AIMS: The cotyledons of Lupinus angustifolius contain large amounts of cell wall storage polysaccharide (CWSP) composed mainly of (1-->4)-beta-linked D-galactose residues in the form of branches attached to a rhamnogalacturonan core molecule. An exo-(1-->4)-beta-galactanase with a very high specificity towards (1-->4)-beta-linked D-galactan has been isolated from L. angustifolius cotyledons, and shown to vary (activity and specific protein) in step with CWSP mobilization. This work aimed to confirm the hypothesis that galactan is the main polymer retrieved from the wall during mobilization at the ultrastructural level, using the purified exo-galactanase as a probe. METHODS: Storage mesophyll cell walls ('ghosts') were isolated from the cotyledons of imbibed but ungerminated lupin seeds, and also from cotyledons of seedlings after the mobilization of the CWSP. The pure exo-(1-->4)-beta-galactanase was coupled to colloidal gold particles and shown to be a specific probe for (1-->4)-beta-D-galactan. They were used to localize galactan in ultrathin sections of L. angustifolius cotyledonary mesophyll tissue during CWSP mobilization. KEY RESULTS: On comparing the morphologies of isolated cell walls, the post-mobilization 'ghosts' did not have the massive wall-thickenings of pre-mobilization walls. Compositional analysis showed that the post-mobilization walls were depleted in galactose and, to a lesser extent, in arabinose. When pre-mobilization ghosts were treated with the pure exo-galactanase, they became morphologically similar to the post-mobilization ghosts. They were depleted of approximately 70% of the galactose residues that would have been mobilized in vivo, and retained all the other sugar residues originally present. Sharply defined electron-transparent wall zones or pockets are associated with CWSP mobilization, being totally free of galactan, whereas wall areas immediately adjacent to them were apparently undepleted. CONCLUSIONS: The exo-(1-->4)-beta-galactanase is the principal enzyme involved in CWSP mobilization in lupin cotyledons in vivo. The storage walls dramatically change their texture during mobilization as most of the galactan is hydrolysed during seedling development.

Cell Wall↗

Three-year post-placement survival of implants mobile at placement.

BACKGROUND: Although rigid fixation of endosseous implants at the time of placement is generally thought to be a prerequisite for successful osseointegration, the Dental implant Clinical Research Group (DICRG) of the Department of Veterans Affairs has reported on implants that integrated despite being mobile at placement. The present study examines the frequency of osseointegration and the 36-month post-placement survival of implants mobile at placement in a prospective, multicenter, longitudinal clinical study of more than 3,000 implants conducted by the DICRG. METHODS: A total of 3,111 implants of 6 different designs were placed in all jaw regions in more than 800 patients at 32 study centers. At the time of this report, 2,770 of these implants had been followed for 36 months post-placement. They included 89 implants that were mobile at placement. Data for demographic variables, implant coating, bone quality, incision type, bone augmentation, and antibiotic usage were recorded. An electronic hand-held probe was used to measure mobility at uncovering and at regular follow-up intervals. RESULTS: Eighty-nine of 2,770 inserted implants were mobile at placement. Results are reported for two periods: from placement to 36 months and from prosthetic loading to 36 months. The latter method eliminated early failures and resulted in substantially higher scores for both mobile implants at placement (95.9% survival from prosthetic loading to 36 months post-placement versus 79.8% from placement to 36 months) and implants not mobile at placement (98.4% versus 93.4%). Mobility at placement was significant to 3-year survival (P < 0.001). Hydroxyapatite (HA) coating improved the performance of implants mobile at placement (91.8% for HA-coated versus 53.6% for non-HA) and those not mobile at placement (97.2% for HA-coated versus 87.4% for non-HA). Radiographic findings suggested that crestal bone response around implants which were mobile versus immobile at placement was similar. CONCLUSIONS: Although implant stability at the time of placement is clearly desirable as seen in the superior 3-year survival of stable implants, it may not be an absolute prerequisite to osseointegration or to long-term survival. Several factors may influence the decision to remove or replace a mobile implant. HA-coating significantly improved the performance of both mobile and immobile implants at placement to 3 years post-placement (P < 0.001).

Adult↗

[Mobility in the community-dwelling elderly and its correlates].

OBJECTIVE: To examine mobility level in community-dwelling elderly using a questionnaire of walking ability over a distance of 1 km and its relationship to activities of daily living (ADL) and quality of life (QOL) indices, and to obtain clues to mobility impairment in the elderly. SUBJECTS AND METHODS: A total of 3,266 community-dwelling elderly aged 60 to 84 years were interviewed with questionnaires for assessing mobility, ADL and QOL levels. The mobility was assessed by walking ability over a distance of 1 km, and the ADL levels were by conventional basic ADL, comprehensive mobility index and the Tokyo Metropolitan Institute of Gerontology Index of Competence, and the QOL levels were by self-rated health, Geriatric Depression Scale (GDS) short-version and Life Satisfaction Index-K (LSIK). They were also asked about diseases for which they regularly consult doctors, and about subjective symptoms. RESULTS: Eighty-seven percent of the subjects responded to the interview, with 86.3% of male responders and 77.6% of female responders answering that they could walk on foot over a distance of 1 km without any difficulty. The percentages of subjects who answered that they could walk but with difficulty or could not walk over a distance of 1 km increased with advancing age. The correlation analysis between 1 km-walking ability and other mobility indices showed that 1 km-walking ability was a better index for identifying a slight to moderate mobility impairment, and that the mobility level was closely associated with daily activity levels in the community-dwelling elderly. The elderly with an impaired mobility had lowered self-rated health, GDS and LSIK scores. After controlling for sex and age, it was shown that prevalences of musculoskeltal (knee arthritis, lower back pain, etc.), cerebrovascular and heart diseases, and complaints of subjective symptoms which were associated with physical frailty, were closely associated with impaired mobility. Hearing and visual disturbances also had a significant relation to a lowered mobility. CONCLUSIONS: Walking ability over a distance of 1 km may be a good index for discriminating differing mobility levels which community-dwelling elderly have intrinsically. The possible etiological factors for a lowered mobility in the elderly include musculoskeletal, cerebrovascular and heart diseases; physical frailty; and hearing and visual disturbances.

Activities of Daily Living↗

[Mobile-phone e-mail use, social networks, and loneliness among Japanese high school students].

PURPOSE: The purposes of this study were to assess the loneliness of Japanese high school students who own and use a mobile phone, to clarify the relationships between students' loneliness and their social network and frequency of use of e-mail feature, and to demonstrate relationships with a student's social network and recognition of the benefits and drawbacks of mobile phone use. METHOD: The participants were 227 students from two classes in each grade of a high school in the Kanto region of Japan. Participants answered a questionnaire covering the UCLA Loneliness Scale as well as questions pertaining to the circumstances of use of their mobile phones, their social networks (e.g., number of friends), and their perceptions of the benefits and drawbacks of mobile phone use. The questionnaires of students owning a mobile phone were analyzed. Total scores for the UCLA Loneliness Scale were calculated, and factor analysis was performed for the benefits and drawbacks. RESULT: A total of 220 questionnaires were returned, for which 94.1 percent of respondents owned a mobile phone. The percentages of male and female respondents were 58% and 42%. Chronbach's alpha for the UCLA Loneliness Scale (total score) was 0.87, a result similar to previous studies with high school and university students. Factor analysis revealed five factors associated with the benefits and drawbacks of mobile phone use. Multiple-regression analysis showed that 42.9% of the variance in "frequency of e-mail use" was explained by grade level, frequency of mobile phone use, and two of the five factors from the benefits and drawbacks ("difficulty of communication," and "possible sleep loss due to nighttime e-mailing"). Stepwise multiple-regression analysis revealed that 24.4% of the variance in UCLA Loneliness Score was explained by gender, the frequency of e-mail use, the number of friends and the presence/absence of a girlfriend or boyfriend. CONCLUSION: Presence of an active social network and frequent e-mailing by mobile phone reduced students' loneliness. The frequency depended on their recognition of the benefits and drawbacks of mobile phone use and by the frequency of mobile phone use. This study established that students appreciate the usefulness of their mobile phone as an immediate communication tool, and are aware of its limitations. Although they experience frustration and lack of sleep (because of nighttime use), students use mobile phones to deepen their friendships.

Adolescent↗

The CXCR4 agonist peptide, CTCE-0021, rapidly mobilizes polymorphonuclear neutrophils and hematopoietic progenitor cells into peripheral blood and synergizes with granulocyte colony-stimulating factor.

OBJECTIVE: Mobilization of hematopoietic stem and progenitor cells (HSPC) by stromal cell-derived factor-1 (SDF-1) has been described; however, sustained adenoviral delivery or N-terminal modification was required for effect and could not be demonstrated with native protein. The aim of this study was to further investigate the SDF-1alpha/CXCR4 axis in HSPC mobilization using CTCE-0021, a cyclized CXCR4 agonist peptide, with comparable bioactivity and improved stability relative to SDF-1alpha. METHODS: Peripheral blood cells and hematopoietic progenitor cells (HPC) were quantitated in mice administered single or multiple doses of CTCE-0021 or SDF-1alpha, or mobilized by granulocyte colony-stimulating factor (G-CSF) in combination with CTCE-0021. Proteases, cytokines, and receptors implicated in HSPC mobilization were evaluated to determine mechanism of action. RESULTS: CTCE-0021 dose-dependently elevated blood neutrophils polymorphonuclear neutrophil [PMN] within 5 minutes that peaked after 1 hour and persisted for 24 hours. PMN mobilization could be maintained by daily dosing. CTCE-0021 mobilized colony-forming unit granulocyte macrophage (CFU-GM), burst-forming unit erythroid (BFU-E), and CFU-granulocyte-erythrocyte-monocyte-megakaryocyte (CFU-GEMM) that peaked within 1 hour after administration, and synergistically enhanced both PMN and HSPC mobilization when combined with G-CSF. Mobilization induced by CTCE-0021 was associated with rapid downregulation of CXCR4 expression on HPC. No appreciable changes in proteases implicated in HPC mobilization were observed. Significantly elevated plasma SDF-1 was detected in mobilized mice, which likely represents CTCE-0021. CONCLUSION: These studies indicate that CTCE-0021 is an efficient and rapid mobilizer of PMN and HPC when used alone and shows synergistic activity when used in combination with G-CSF. The mobilizing effect of this peptide appears to be mediated by downregulation of the CXCR4 receptor on HPC and altered chemokine gradient.

Animals↗

Combining G-CSF with a blockade of adhesion strongly improves the reconstitutive capacity of mobilized hematopoietic progenitor cells.

OBJECTIVE: Mobilization of hematopoietic progenitor cells is achieved mainly by application of growth factors and, more recently, by blockade of adhesion. In this report, we describe the advantages of a combined treatment with granulocyte colony-stimulating factor (G-CSF) and anti-VLA4 (CD49d)/anti-CD44 as compared to treatment with the individual components. MATERIALS AND METHODS: Mobilization by intravenous injection of anti-CD44, anti-VLA4, or G-CSF was controlled in spleen and bone marrow with regard to frequencies of multipotential colony-forming unit (C-CFU), marrow repopulating ability, long-term reconstitution, recovery of myelopoiesis, and regain of immunocompetence. RESULTS: Mobilization by anti-CD44 had a strong effect on expansion of early progenitor cells in the bone marrow, while the recovery in the spleen was poor. In anti-CD49d-mobilized noncommitted and committed progenitors, progenitor expansion was less pronounced, but settlement in the spleen was quite efficient. Thus, anti-CD44 and anti-CD49d differently influenced mobilization. Accordingly, mobilization and recovery after transfer were improved by combining anti-CD44 with anti-CD49d treatment. Mobilization by G-CSF was most efficient with respect to recovery of progenitor cells in the spleen. However, when transferring G-CSF-mobilized cells, regain of immunocompetence was strongly delayed. This disadvantage could be overridden when progenitor cells were mobilized via blockade of adhesion and when expansion of these mobilized progenitor cells was supported by low-dose G-CSF only during the last 24 hours before transfer. CONCLUSION: Mobilization of pluripotent progenitor cells via antibody blockade of CD44 or CD49d or via G-CSF relies on distinct mechanisms. Therefore, the reconstitutive capacity of a transplant can be significantly improved by mobilization regimens combining antibody with low-dose G-CSF treatment.

Animals↗

Enhancement of the anti-tumor activity of a peripheral blood progenitor cell graft by mobilization with interleukin 2 plus granulocyte colony-stimulating factor in patients with advanced breast cancer.

OBJECTIVE: Autologous interleukin 2 (IL-2)-activated natural killer (NK) cells kill a broad spectrum of tumor targets, including breast cancer. We hypothesized that mobilization with IL-2 and granulocyte colony-stimulating factor (G-CSF) for collection of peripheral blood progenitor cells (PBPC) may enhance the anti-tumor activity of the graft in autograft recipients. We determined the dose-limiting toxicity and maximum tolerated dose of subcutaneous IL-2 given with G-CSF for PBPC mobilization, the ability of IL-2 + G-CSF mobilized stem cells to reconstitute hematopoiesis, and the in vitro immunologic function of the graft in patients with advanced breast cancer. MATERIALS AID METHODS: Forty-three women with stage IIIA/B or metastatic breast cancer underwent mobilization of PBPC with IL-2 administered subcutaneously for 14 days along with G-CSF for the latter 7 days. IL-2 was given in a dose-escalated manner, with the maximum tolerated dose determined to be 1.75 x 10(6) IU/m(2)/day. Fifteen women with stage IIIA/B or metastatic breast cancer underwent G-CSF mobilization alone and served as a control group. RESULTS: [corrected] Fifty-two percent of the patients mobilized with 1L-2 at the maximum tolerated dose reached the target number of CD34(+) cells for transplantation with three aphereses compared to 93% of control patients who were mobilized with G-CSF alone. [corrected] There was no significant impact on time to engraftment of neutrophils or platelets using either mobilization regimen. The addition of subcutaneous IL-2 to mobilization increased the cytotoxicity of IL-2-activated mononuclear cells from the PBPC product against the breast cancer cell target, MCF-7, and increased the percentage of NK cells and activated T cells in the PBPC product. The enhanced NK cell number was sustained in the early posttransplant period. CONCLUSIONS: [corrected] IL-2 + G-CSF mobilization is safe, may lead to a more immunologically functional graft without impairing hematologic recovery, and thus merits further exploration to evaluate the clinical anti-tumor efficacy of these immunocompetent grafts. [corrected] Limitations of this combined approach to stem cell mobilization include a decrease in the number of CD34(+) cells mobilized with the combined cytokines and the short duration of the increased number of anti-tumor effector cells after transplant.

Adult↗

Poor mobilization is an independent prognostic factor in patients with malignant lymphomas treated by peripheral blood stem cell transplantation.

Haemopoietic stem cell therapy is an increasingly adopted procedure in the treatment of patients with malignant lymphoma. In this retrospective analysis, we evaluated 262 patients, 57 (22%) with Hodgkin's and 205 (78%) with non-Hodgkin's lymphomas (NHL), and 665 harvesting procedures in order to assess the impact of poor mobilization on survival and to determine the factors that may be predictive of CD34(+) poor mobilization. The mobilization chemotherapy regimens consisted of high-dose cyclophosphamide in 92 patients (35.1%) and a high-dose cytarabine-containing regimen (DHAP in 87 patients -(33.2%), MAD in 83 (31.7%)). The incidence of poor mobilizers (<2 x 10(6) CD34(+) cells/kg) was 17.9% overall, with a 10% of very poor mobilizers (< or = 1 x 10(6)/kg). Refractory disease status and chemotherapeutic load (>3 regimens) before mobilization played a negative role and were associated with poor mobilization. Survival analysis of all harvested patients showed an overall survival at 3 years of 71% in good mobilizers vs 33% in poor mobilizers (P=0.002). The event-free survival at 3 years was 23% in poor mobilizers and 58% in good mobilizers (P=0.04). We conclude that in NHL patients, poor mobilization status is predictive of survival.

Adult↗

High steady-state plasma levels of flt3-ligand in the peripheral blood is a good predictor for poor mobilization of CD34+ PBSC in patients undergoing high-dose chemotherapy and stem cell rescue.

flt3-ligand (flt3-L) is a very effective mobilizer of hematopoietic stem cells (HSC) and is capable of inducing multilineage hematopoietic cell differentiation both in vivo and in vitro. We measured, by ELISA, the plasma peripheral blood flt3-L concentrations in 28 non-Hodgkin's lymphoma (NHL) patients before and after mobilization with three different mobilization regimens, including priming with cyclophosphamide (CY) plus G-CSF, CY plus GM-CSF, and CY plus GM-CSF (8 days) followed by G-CSF. We also determined the levels of flt3-L in the peripheral blood during four apheresis collections and 6 months after transplantation. The steady-state level of flt3-L in NHL patients (n = 18) who mobilized > or =2 x 10(6) CD34+ cells/kg in four apheresis collections was 34 +/- 4 pg/ml and was similar to the levels observed in 10 normal controls (27 +/- 7, p = 0.1) regardless of the mobilization protocol used. In contrast, patients who failed to mobilize a total of >0.4 x 10(6) CD34+ cells/kg in two consecutive apheresis collections (n = 10) had flt3-L levels of 106 +/- 11 pg/ml, significantly higher (p = 0.006) than that of the good mobilizers group, regardless of the mobilization protocol used. Similar results were observed in 29 multiple myeloma (MM) patients. A mean of 23.8 +/- 7.9 pg/ml and 450 +/- 85 pg/ml flt3-L was obtained in the good mobilizers (n = 24) and the nonmobilizers (n = 5) groups of patients, respectively. Statistical analysis revealed a significant difference (p = 0.0006) between the two groups of MM patients, but no correlation was observed between the levels of flt3-L and CD34+ cell/microl, in mobilized peripheral blood. Our results also suggest that measurement of plasma levels of flt3-L before mobilization can be clinically useful to predict for patients with poor mobilization outcome.

Adjuvants, Immunologic↗

The role of diagnosis in patients failing peripheral blood progenitor cell mobilization.

BACKGROUND: Failure to mobilize PBPCs for auto-logous transplantation has mostly been attributed to previous therapy and poses therapeutic problems. STUDY DESIGN AND METHODS: The role of underlying disease was analyzed in 17 of 73 (23%) patients with PBPC mobilization failure, and secondary mobilization with high-dose filgrastim was attempted. RESULTS: Of 16 patients with acute leukemia, 13 (81%) mobilized poorly. In contrast, of 57 patients with non-Hodgkin's lymphoma, Hodgkin's lymphoma, multiple myeloma, and solid tumor, 53 (93%, p < 0.001) showed good PBPC mobilization. Relapsed disease did not predispose to poor mobilization. As secondary mobilization attempt, 7 patients received 25 micro g per kg per day filgrastim without chemotherapy leading to a 3.7 +/- 2.8-fold (SD) increase in the maximum number of circulating CD34+ cells (p = 0.104). PBPC apheresis yielded 3.3 (+/-0.5) x 10(6) CD34+ cells per kg of body weight in 5 patients. Four poor mobilizers received 50 micro g per kg per day filgrastim as second or third mobilization attempt. Circulating CD34+ cells in these patients increased by 1.5 (+/-0.7) compared with the primary G-CSF application. CONCLUSION: Selective PBPC mobilization failure was seen in patients with acute leukemia whereas remarkably good mobilization was seen in other malignancies. Increasing the filgrastim dose to 25 micro g per kg per day may allow PBPC collection in patients failing PBPC mobilization.

Adult↗

Childhood environment, intergenerational mobility, and adult health--evidence from Swedish data.

STUDY OBJECTIVE: The aim was to examine whether body height is associated with intergenerational social mobility, and to determine the importance of intergenerational mobility for adult health. DESIGN: Information from a survey conducted by Statistics Sweden on a randomly selected sample was supplemented with mortality data during a six year follow up. PARTICIPANTS: The sample was identified in 1980-81 and comprised 14,757 persons aged 16-74 years. The non-response rate was 14%. In the current study a subsample of 9203 persons aged 30-74 years at the time of the interview was used. MEASUREMENTS AND MAIN RESULTS: Information on adult height, socioeconomic status during childhood and in adult life, self perceived general health, and self reported longstanding illness at the time of the interview was supplemented with mortality data during the follow up period. The direction of the intergenerational mobility was defined as upward mobility, downward mobility, and no intergenerational mobility. The chances of falling into each of these three groups for tall, medium, and short persons were compared. The three mobility groups were also compared with regard to general health, longstanding illness and early death. The tall third of the sample was upwardly mobile to a larger extent than the short third, while the short third was more likely to be downwardly mobile. The upwardly mobile group perceived their health as bad much less than was expected. It also included a smaller number of persons with longstanding illness. Mortality, however, was not lower in this group. CONCLUSIONS: Childhood environment influences height, height is linked to upward mobility, and upward mobility is linked to better health. This is one way in which childhood environment has an impact on adult health.

Adult↗

Health-related social mobility: a comparison of currently employed men and women in Britain and Finland.

Selective health-related social mobility has been suggested as one possible explanation for health inequalities. The aim of this paper is to examine the size and significance of the contribution which health-related social mobility makes to social class differences in health. We do this by examining the association between intergenerational social mobility and health among currently employed men and women in Britain and Finland. We used comparable nationally representative interview surveys from Britain and Finland. The British data is derived from the General Household Survey for 1988 and 1989, and the Finnish data from the 1986 Survey on Living Conditions. Health measures included limiting long-standing illness and self-assessed health as below good. Social mobility was measured comparing the respondent's class of origin (father's occupation) with his/her class of destination (own current occupation). Social structural changes and related social mobility have been more dramatic in Finland than in Britain during the last few decades. Downward mobility has been relatively rare, and mobility has taken place predominantly upwards. In Finland downward mobility from upper non-manual to manual worker was associated with a somewhat higher risk of limiting long-standing illness than expected among men as well as women. However, there was no statistically significant interaction effect on health between the respondent's father's occupational class and his/her own current class. In Britain, neither self-assessed health nor limiting long-standing illness were related to social mobility. Some weak evidence for health-related downward social mobility was found for currently employed Finnish men and women, but not for their British counterparts. Moreover, the evidence is weaker for self-assessed health than for limiting long-standing illness. Where social mobility may have been health-related, it concerns very rare and small groups; therefore health inequalities among the currently employed cannot be explained by intergenerational health-related social mobility.

Adult↗

Anti-LFA-1 blocking antibodies prevent mobilization of hematopoietic progenitor cells induced by interleukin-8.

Previously, we have shown that interleukin (IL)-8 induces the rapid (15 to 30 minutes) mobilization of hematopoietic progenitor cells (HPC) in mice. Because integrins are essential for adhesion and transendothelial migration of HPC, we studied the involvement of the beta2-integrin leukocyte function-associated antigen-1 (LFA-1) in IL-8-induced mobilization. After a single injection of blocking anti-LFA-1 antibodies, no mobilization of colony-forming cells was observed. In addition, when mice were pretreated with anti-LFA-1 or saline and subsequently injected with 30 microg of IL-8, mobilization of HPC was completely blocked. We showed that this was not due to anti-LFA-1 antibodies affecting colony formation, as addition of anti-LFA-1 antibodies to colony cultures in semisolid medium had no inhibitory activity. Also, anti-intercellular adhesion molecule (ICAM)-1 antibodies, directed to the main ligand of LFA-1 significantly inhibited the IL-8-induced mobilization. Furthermore, IL-1-induced mobilization was significantly inhibited by anti-LFA-1 antibodies. Because LFA-1 is reported to be expressed on more differentiated HPC, it was considered that the IL-8-induced mobilization of more primitive HPC would not be blocked by anti-LFA-1 antibodies. Transplantation of blood-derived mononuclear cells (MNC) from IL-8-mobilized animals pretreated with anti-LFA-1 antibodies protected only 25% of lethally irradiated recipient mice, whereas the radioprotection rate of control mice transplanted with MNC derived from IL-8-mobilized animals was 86% (P < .01). Anti-LFA-1 antibodies did not interfere with stem cell homing, as transplantation of IL-8-mobilized blood MNC, incubated in vitro with these antibodies resulted in 100% radioprotection. We conclude that anti-LFA-1 antibodies completely prevent the rapid mobilization of colony-forming cells and of cells with radioprotective capacity induced by IL-8. These results indicate a major role for the beta2-integrin LFA-1 in the IL-8-induced mobilization of hematopoietic stem cells.

Animals↗

Mobile phone ownership and use among school children in three Hungarian cities.

In spite of rapid worldwide increase in mobile phone use and public concerns about associated potential health effects, little is known about patterns of mobile phone ownership and use in the general population and among children. In April 2005, we conducted a survey of mobile phone ownership and use among fourth grade school children in three Hungarian cities. From 24 schools, 1301 student filled out a short, self-administered questionnaire on basic demographics, mobile phone ownership, pattern of mobile phone use, and after-school activities. Overall, 989 students (76%) owned a mobile phone. Three hundred thirteen students (24%) used a mobile phone daily to make phone calls, and an additional 427 students (33%) used mobile phones for phone calls at least several times per week. Sixty-six students (5%) sent text messages daily and an additional 308 students (24%) sent text messages at least several times per week. Girls, children with no siblings, children who were members of a sport club, and children who played computer games daily were more likely to own and use mobile phones regularly. A higher number of socially disadvantaged children in a class predicted lower likelihood of regular mobile phone use among children. Our results suggest that mobile phone ownership and regular use is highly prevalent among school children in Hungary. Due to rapid changes in ownership patterns follow up surveys will be required to obtain information on temporal trends and changes in mobile phone ownership and pattern of use among school children.

Cell Phone↗

Haematological recovery after high-dose consolidation chemotherapy with peripheral blood progenitor cell rescue: the effects of the mobilization regimen and post-transplant growth factors.

PURPOSE: Peripheral blood progenitor cells (PBPC), mobilized by chemotherapy, growth factors (GF) or the combination of these modalities are currently used in most autologous transplants settings. Patient selection factors and infused cell numbers have been related to the rate of haematological recovery after transplant (p-Tx). The effect of the mobilization regimen on haematological recovery has rarely been reported and is addressed herein. The value of p-Tx GF use is also evaluated. METHODS: A literature review identified studies reporting both mobilization results and haematological recovery (time to ANC > 0.5 or 1.0 x 10(9)/1 and PLT > 20 or 50 x 10(9)/1). The studies are listed in tables showing the mobilization regimen, disease, infused CD34+ cell and CFU-GM dose, p-TX GF use and haematological recovery. The ranges of recovery times for each transplant setting are summarized in a figure in addition to the ranges of recovery times using GF after autologous bone marrow transplants in controlled studies. RESULTS: Transplantation of cells mobilized by G-CSF results in faster haematological recovery than transplantation of cells mobilized by GM-CSF. This difference disappears when chemotherapy is included in the mobilization regimen. GF have minimal effect on haematological recovery after transplantation of PBPC mobilized by chemotherapy plus GF and some effect on neutrophil recovery after transplants of PBPC mobilized by GF only. CONCLUSIONS: Recovery after PBPC transplantation depends on the mobilization method and is best predictable when mobilization occurs with chemotherapy plus GF. In this situation, the value of post-transplant growth factors is questionable. Careful choice of the mobilization method, including optimal timing of leucapheresis and patient selection factors, determine the leucapheresis yield and thus the rate of haematological recovery.

Antineoplastic Combined Chemotherapy Protocols↗

Progressive versus catastrophic loss of the ability to walk: implications for the prevention of mobility loss.

OBJECTIVES: Loss of mobility is an important functional outcome that can have devastating effects on quality of life and the ability of older persons to remain independent in the community. Although a large amount of research has been done on risk factors for disability onset, little work has focused on the pace of disability progression. This study characterizes the development of severe walking disability over time and evaluates risk factors and subsequent mortality as they relate to mobility disability with progressive or catastrophic onset. DESIGN: Population-based prospective cohort study with annual follow-up assessments for up to 7 years SETTING: Three communities of the Established Populations for Epidemiologic Studies of the Elderly. PARTICIPANTS: There were 5,355 persons not disabled at baseline and the first follow-up who had adequate data available to classify mobility disability during subsequent follow-ups. MEASUREMENTS: Severe mobility disability was defined as the need for help from a person to walk across a room or inability to walk across a room. Those developing severe mobility disability were classified as having progressive mobility disability if they had been unable to walk half a mile in either of the prior 2 years. They were classified as having catastrophic mobility disability if they reported having been able to walk half a mile in two previous annual interviews. RESULTS: The overall incidence of severe mobility disability was 11.6 cases/1,000 person years. Those age 85 and older or having three or more chronic conditions at baseline were significantly more likely to develop progressive disability than catastrophic disability. Stroke, hip fracture, and cancer occurring during follow-up were associated with very high risk of severe mobility disability. For stroke and hip fracture, the risk was twice as high for catastrophic disability as for progressive disability, but this difference did not reach statistical significance. Risk for catastrophic disability from cancer was significantly greater than for progressive disability. Half of catastrophic disability subjects had stroke, hip fracture, or cancer in the year immediately preceding this disability. Incident heart attack did not predict severe mobility disability. Among those who developed severe mobility disability, type of disability did not influence subsequent survival for the first 3 years, but beyond 3 years those with catastrophic disability had a relative risk of death of 0.4 (95% confidence interval 0.2-0.9) compared with those with progressive disability. CONCLUSION: The observation that risk factors and mortality outcomes were both different for progressive and catastrophic mobility disability supports the value of ascertaining the pace of disability development as a useful characterization of disability. Further progress in developing prevention and treatment strategies may be made by taking the pace of disability development into account.

Aged↗

Mobility status after inpatient stroke rehabilitation: 1-year follow-up and prognostic factors.

OBJECTIVES: To evaluate the stability of mobility status achieved by stroke patients during hospital rehabilitation treatment over time and to identify reliable prognostic factors associated with mobility changes. DESIGN: Follow-up evaluation in consecutive first-ever stroke patients 1 year after hospital discharge. Multiple logistic regressions were used to analyze increases and decreases in Rivermead Mobility Index (RMI) scores (dependent variables) between discharge and follow-up. Independent variables were medical, demographic, and social factors. SETTING: Rehabilitation hospital. PATIENTS: A cohort of 155 patients with sequelae of first stroke, with a final sample of 141. MAIN OUTCOME MEASURES: Mobility status at 1-year follow-up, as measured by the RMI, and odds ratios (OR) for improvement and decline in mobility. RESULTS: Functionally, 19.9% improved the mobility levels achieved during the inpatient rehabilitation treatment; levels of 42.6% worsened. Patients with global aphasia (OR = 5.66; 95% confidence interval [CI], 1.50-21.33), unilateral neglect (OR = 3.01; 95% CI, 1.21-7.50), and age 75 years or older (OR = 5.77; 95% CI, 1.42-23.34) had a higher probability of mobility decline than the remaining patients. Postdischarge rehabilitation treatment (PDT), received by 52.5% of the final sample, was significantly and positively associated with mobility improvement (OR = 5.86; 95% CI, 2.02-17.00). Absence of PDT was associated with a decline in mobility (OR = 3.73; 95% CI, 1.73-8.04). CONCLUSIONS: In most cases, mobility status had not yet stabilized at hospital discharge. PDT was useful in preventing a deterioration in mobility improvement achieved during inpatient treatment and in helping increase the likelihood of further mobility improvement.

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