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High-dose ara-C with autologous peripheral blood progenitor cell support induces a marked progenitor cell mobilization: an indication for patients at risk for low mobilization.

A high-dose (HD) chemotherapy scheme was designed for the collection of large numbers of peripheral blood progenitor cells (PBPC) in lymphoma patients who were candidates for myeloablative therapy with autograft. The scheme included the sequential administration of HD cyclophosphamide (CY) (7 g/m(2)) and HD ara-C (2 g/m(2) twice a day for 6 consecutive days), followed by final consolidation with PBPC autograft. PBPC harvests were scheduled following both HD CY and HD ara-C. To minimize hematologic toxicity, small aliquots of PBPC ( 20 circulating CD34(+) cells/microl, whereas the remaining 19 'low-mobilizer' patients did not reach this cut-off value. In spite of poor mobilization after HD CY, 16 out of 19 low mobilizers provided good harvests following HD ara-C; overall, median collected CD34(+) cells x 10(6)/kg were 1.4 (0-3.1) and 10.2 (0-37) after HD CY and HD ara-C, respectively (P = 0.00007). Similar patterns were observed when PBPC were evaluated by CFU-GM/kg. Complete and durable hemopoietic reconstitution followed autograft with post HD ara-C PBPC. Within the high-mobilizer group, 88 patients received HD ara-C and 79 (90%) still showed high mobilization; overall, median collected CD34(+)cells x 10(6)/kg were 17.8 (range 3-94) and 19 (range 0-107) after HD CY and HD ara-C respectively (P = NS). Thus, the scheme allowed sufficient PBPC collections for autografting in low mobilizer patients; in addition, the scheme could be considered whenever extensive chemotherapy debulking is needed prior to PBPC collection.

Adolescent↗

Proteolytic enzyme levels are increased during granulocyte colony-stimulating factor-induced hematopoietic stem cell mobilization in human donors but do not predict the number of mobilized stem cells.

Previous studies from our laboratory indicate that functional, mature neutrophils are essential for interleukin-8 (IL-8)-induced stem cell mobilization. To study a possible role of neutrophils in granulocyte colony-stimulating factor (G-CSF) induced hematopoietic mobilization, we assessed the number of circulating CD34+ cells in healthy allogeneic stem cell donors on days 3, 4, and 5 of mobilization for comparison with the number of peripheral blood neutrophils and the plasma levels of IL-8, Flt3 ligand (FL), matrix metalloproteinase-9 (MMP-9), and human neutrophil elastase (HNE). Thirty-seven of 45 donors required 1 day of apheresis to obtain 5 x 10(6) CD34+/kg recipient body weight (high responders), the remaining 8 donors required 1 extra day of apheresis on day 6 (low responders). On day 5, CD34+ numbers in the blood were significantly highe in high responders (116 x 10(3) +/- 10.4/ml) than in low responders (54.1 x 10(3) +/- 10.3, p < 0.001). In all donors, MMP-9 and HNE levels were increased compared to nonmobilized individuals, but in high responders, plasma MMP-9 levels on days 3-5 of mobilization were substantially higher than in low responders (p < or = 0.02 for MMP-9 and p = 0.89, p = 0.05 and p = 0.52 for HNE on days 3, 4, and 5, respectively). These results are in accordance with the hypothesis that neutrophils play a role in G-CSF-induced mobilization through the release of proteases such as MMP-9 and elastase. No change in plasma levels of IL-8 or Flt3 ligand was observed, suggesting that these cytokines do not play a role in stem cell mobilization. However, because stem cell numbers could not be predicted by proteolytic enzyme levels and/or neutrophil numbers, other undefined factors may be more important.

Antigens, CD34↗

Mobility performance of low-vision adults using an electronic mobility aid.

Visually impaired people rank obstacle location and identification as two of the most important mobility problems faced. Traditional mobility aids (the long cane) provide information about where an object is located but only within their limited (one metre) range. Although objects are located when traditional aids are used, it is unlikely that they are identified. The Bristol Mobility Aid (BMA) is an electronic travel aid that presents scene images to remaining residual vision in a number of view formats. Previous work has suggested visually impaired observers have better static object recognition using this aid. We investigated the mobility performance of subjects with retinitis pigmentosa using the BMA by determining the percentage preferred walking speed (PPWS), and the number of errors made with three different BMA headset views on an indoor mobility course. We found low-vision subjects had significantly reduced PPWS in two of the three headset views and interestingly, sighted subjects had significantly reduced PPWS when using the BMA in all three views. The numbers of errors made were significantly higher across all vision groups when the BMA was worn. We found that the BMA does not currently increase mobility in the visually impaired. Results are discussed in terms of modifications that could be made to the aid and methodological limitations.

Aged↗

Re-thinking the analysis of intergenerational social mobility: a comment on John W. Fox's "Social class, mental illness, and social mobility".

The method of analyzing social mobility described by Fox (1990) is flawed in its adjustment for between-group differences in destination status when estimating the extent of the mentally ill's mobility as compared with the general population. Use of the recommended model with hypothetical data sets resulted in a significant finding when no overall upward or downward mobility occurred, and a non-significant result when the downward mobility of a psychotic group was contrived to be massive. An alternative model for the test of group differences in mobility is suggested within the framework of log-linear analysis commended by Fox (1990). This method indicated significantly more downward and less upward mobility in mentally ill groups when data from four studies were re-analyzed. We conclude that the weight of evidence from published studies supports the notion of social selection-drift, although this does not imply the inconsequence of social factors in the aetiology of schizophrenia (and other psychoses) or in its prognosis and occupational consequences.

Humans↗

Segmental mobility of the lumbar spine during a posterior to anterior mobilization: assessment using dynamic MRI.

OBJECTIVES: To quantify segmental mobility of the lumbar spine during a posterior to anterior spinal mobilization procedure. DESIGN: Descriptive study using dynamic magnetic resonance imaging. BACKGROUND: The posterior to anterior spinal mobilization procedure is frequently used in the assessment and management of spinal dysfunction. How this procedure influences segmental spinal motion however, is not known. METHODS: Eleven asymptomatic subjects were positioned prone within a vertically open double donut design magnetic resonance imaging system. An anteriorly directed force was applied manually at each lumbar spinous process while magnetic resonance images were obtained continuously in the sagittal plane. The intervertebral angle was used to quantify segmental motion. RESULTS: The direction of motion at the tested segment was always extension, with values ranging from 1.2 (SD 2.2) at L2 to 3.0 (SD 2.3) degrees at L5. When the force was applied at L3, L4 and L5, the non-tested (adjacent) segments also were observed to move into extension. However, when the posterior to anterior force was applied at L1 and L2 the three caudal segments moved into flexion. CONCLUSIONS: Posterior to anterior spinal mobilization consistently caused extension at the tested segment, while the motion of the collective lumbar spine was either an increase or decrease in lordosis depending on the segment at which the force was applied. RELEVANCE: Passive movement techniques are commonly used to identify the symptomatic lumbar segment(s) and can be used as a treatment aimed at increasing mobility and/or decreasing pain. Knowledge of how this procedure influences segmental motion of healthy spines is important in understanding how altered mobility is related to symptoms.

Adult↗

Effects of exposure to low pH on the lateral mobility of influenza hemagglutinin expressed at the cell surface: correlation between mobility inhibition and inactivation.

To investigate the possible role of viral glycoprotein mobility in membrane fusion, fluorescence photobleaching recovery was employed to study the effects of exposure to mildly acidic pH (required to convert many viral fusion proteins to the fusion-active form) on the lateral mobility of influenza hemagglutinin (HA) proteins expressed at the surface of transfected cells. HA proteins from two different strains were compared: X:31 HA, which is activated by a brief exposure to pH 4.9 but is irreversibly inactivated at longer exposure times, and HA from A/Japan/305/57, which is relatively stable to inactivation at this pH [Puri, A., Booy, F.P., Doms, R.W., White, J.M., & Blumenthal, R. (1990) J. Virol. 64, 3824-3832]. The HA proteins from both strains, expressed in CV-1 cells using VS-40 vectors, exhibited relatively unrestricted lateral diffusion at the cell surface. The high mobility persisted following a brief exposure (1 min) to pH 4.9 to mediate conversion to the fusogenic state. Longer times (up to 15 min) of preincubation at pH 4.9 inhibited the lateral mobility of X:31 HA (the lateral diffusion rate was markedly reduced, followed by immobilization) but not of A/Japan HA, whose fusion activity is resistant to such treatment. Inhibition of the lateral mobility of X:31 HA due to preincubation at low pH was not specific to the CV-1 cells and was found also in a CHO cell line stably expressing this protein. The results presented demonstrate a close correlation between loss of mobility and inactivation of fusogenic activity, in accord with the notion that lateral motion of the HA proteins is required for fusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Field asymmetric waveform ion mobility spectrometry studies of proteins: Dipole alignment in ion mobility spectrometry?

Approaches to separation and characterization of ions based on their mobilities in gases date back to the 1960s. Conventional ion mobility spectrometry (IMS) measures the absolute mobility, and field asymmetric waveform IMS (FAIMS) exploits the difference between mobilities at high and low electric fields. However, in all previous IMS and FAIMS experiments ions experienced an essentially free rotation; thus the separation was based on the orientationally averaged cross-sections Omega(avg) between ions and buffer gas molecules. Virtually all large ions are permanent electric dipoles that will be oriented by a sufficiently strong electric field. Under typical FAIMS conditions this will occur for dipole moments >400 D, found for many macroions including most proteins above approximately 30 kDa. Mobilities of aligned dipoles depend on directional cross-sections Omega(dir) (rather than Omega(avg)), which should have a major effect on FAIMS separation parameters. Here we report the FAIMS behavior of electrospray-ionization-generated ions for 10 proteins up to approximately 70 kDa. Those above 29 kDa exhibit a strong increase of mobility at high field, which is consistent with predicted ion dipole alignment. This effect expands the useful FAIMS separation power by an order of magnitude, allowing separation of up to approximately 10(2) distinct protein conformers and potentially revealing information about Omega(dir) and ion dipole moment that is of utility for structural characterization. Possible approaches to extending dipole alignment to smaller ions are discussed.

Electrochemistry↗

Elevation of extracellular adenosine mobilizes haematopoietic progenitor cells and granulocytes into peripheral blood and enhances the mobilizing effects of granulocyte colony-stimulating factor.

We tested the capabilities of drugs elevating extracellular adenosine and of granulocyte colony-stimulating factor (G-CSF), given alone or in combination, to mobilize haematopoietic progenitor cells for granulocytes and macrophages (GM-CFC) and granulocytes into peripheral blood. Elevation of extracellular adenosine was induced by joint administration of dipyridamole (DP), a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP) serving as an adenosine prodrug. DP + AMP, G-CSF or all these drugs in combination were administered either singly or repeatedly in a 4-d treatment regimen. Elevation of extracellular adenosine was found to mobilize significantly both GM-CFC and granulocytes after both single and repeated administration of DP + AMP. These results show that the elevation of extracellular adenosine presents a potent mechanism for mobilization of GM-CFC and granulocytes into the blood. When the combination of DP + AMP + G-CSF was given under the 4-d regimen, the mobilizing effects of its administration were additive when compared with those of DP + AMP alone or G-CSF alone. The observed ability of the drugs elevating extracellular adenosine to enhance the mobilizing action of G-CSF points out possible practical utilization of the findings presented here. This conclusion is further supported by the results of an additional experiment which indicate that blocking of haemodynamic side effects of drugs elevating extracellular adenosine by noradrenaline does not suppress their mobilizing effects.

Adenosine↗

CD34+ cell positive selection from mobilized peripheral blood by an indirect immunomagnetic method: effect of the type of mobilization and assessment of tumor depletion ability.

Mobilized peripheral blood has been shown to be a suitable source of hematopoietic progenitor cells for autologous transplantation in oncologic patients. However, tumor cell contamination can potentially occur, although to a lesser extent than in the bone marrow. CD34+ cell positive selection has been developed as a system for the ex vivo purging of remaining tumor cells when used in mobilized peripheral blood. This method has shown a lower purification potential than that obtained with bone marrow or cord blood. The reason for this is not clear, but different groups have tried to improve the purity and yield of the positive selection on mobilized peripheral blood by predepletion of nonlymphoid cell populations, since they can induce nonspecific binding. The present study was designed to test an indirect immunomagnetic CD34+ cell selection method to make it reproducible, feasible, and effective for purging mobilized peripheral blood. Twenty-nine samples from mobilized peripheral blood were tested. The median starting CD34+ percentage was 0.8 (0.3%-4.2%), and the median final purity was 87% (32.7%-99.7%), with a median yield of 44.8% (15%-83.5%). The highest purity was reproducibly achieved when the starting percentage of CD34+ cells was higher than 0.65% (median purity 93.7, range 81%-99.7%, CV 6%) on samples obtained from patients primed with chemotherapy alone or chemotherapy plus recombinant human granulocyte-colony stimulating factor. No relation was found between the content of contaminating nucleated cells and the final CD34+ cell purity. This method showed a depletion capacity, assessed by PCR on samples contaminated with K562 leukemic cells, of about 3 logs. These results indicate that this indirect immunomagnetic method can produce high purity CD34+ cell fractions from mobilized peripheral blood with a high efficiency of tumor depletion.

Antigens, CD34↗

Mobile phones in the hospital: improved mobile communication and mitigation of EMI concerns can lead to an overall benefit to healthcare.

There is a growing trend in hospitals throughout the world to incorporate mobile phones and other wireless technology to offer more efficient, cost effective, and higher quality healthcare. Misunderstanding of mobile phone systems, electromagnetic interference with medical devices, and available management solutions, however, has led to a wide range of inconsistent hospital policies. Recent reviews and commentaries on the subject have provided inconsistent and in some cases factually incorrect information that confuses the issue. At one extreme, unmanaged use of mobile phones in areas where life-critical medical devices are in operation can result in atypical situations that may place patients at risk. At the other extreme, overly-restrictive policies based upon speculation may deny benefits by acting as an obstacle to technology. Overly-restrictive policies may also not address growing and legitimate communication needs of patients and visitors in times of crisis. While it may not be feasible for hospitals to manage every mobile phone handset that is randomly brought into their facility without certain limits on use in areas where life-critical devices are commonly in operation, restrictions are not usually necessary throughout the entire facility. Restrictive policies are also better facilitated when easily accessible areas are designated where mobile phone use is encouraged. Controlled mobile phone systems for use by doctors and staff for hospital-specific communication, by contrast, can operate compatibly throughout the entire hospital facility with appropriate system design and management, even in sensitive areas, and such systems have already been deployed in a number of hospitals throughout the U.S.

Cell Phone↗

Assessing environmentally determined mobility disability: self-report versus observed community mobility.

OBJECTIVES: To examine the test-retest reliability and concurrent validity of a new self-report measure of mobility function by comparing it with observed mobility, self-reported activity of daily living (ADL) function, and performance-based measures of gait and balance. DESIGN: Cross-sectional study involving two groups of older adults. SETTING: Community sites in Seattle, Washington, and Waterloo, Ontario, Canada. PARTICIPANTS: Fifty-four adults aged 70 and older, recruited. MEASUREMENTS: Subjects completed the Environmental Analysis of Mobility Questionnaire (EAMQ), reporting frequency of encounter and avoidance of 24 features of the physical environment, grouped into eight dimensions, on two occasions 1 week apart. Subjects were observed and videotaped during six trips into the community; frequency of encounters with environmental features within the eight dimensions was recorded. EAMQ encounter and avoidance scores were compared with observed environmental encounters, with disability in ADLs and instrumental ADLs (IADLs), and lower extremity functional measures including the Short Physical Performance Battery (SPPB) and the Berg Balance Test. RESULTS: EAMQ test-retest reliability was high for all eight dimensions (intraclass correlation coefficient range=0.81-1.0) and for summary encounter (0.98) and avoidance (0.96) scores. Observed mobility was significantly correlated (Spearman correlation = r) with EAMQ summary encounter (r=0.66) and avoidance (r=-0.58) scores. Moderate correlations were present between the EAMQ (encounter or avoidance) and observed mobility in the distance, temporal, terrain, posture, load, and density dimensions but not in the attention and ambient dimensions. EAMQ encounter/avoidance was significantly associated with ADL and IADL ability and performance on the SPPB and Berg Balance Test. CONCLUSION: Self-reported frequency of encounter and avoidance of specific environmental features appears to be a valid method for determining environmentally specific mobility disability but needs to be confirmed in a larger sample.

Activities of Daily Living↗

A synthesis of selected literature on mobility: a basis for studying impaired mobility.

The concept of mobility can be found in the nursing diagnosis literature as impaired physical mobility, which is generally defined as limitations of physical movement within the environment. In this context, mobility is viewed within the confines of the physical realm. This conceptualization is restrictive in scope and therefore does not provide much direction for the nurse clinician. The theoretical basis of mobility must be strengthened to generate the knowledge necessary to understand impaired physical mobility. The purpose of this article is to present a consolidated review of the literature related to the concept of mobility. Studies from the social sciences are explored. Conceptual orientations from the health literature also are discussed. Finally, the nursing perspective is examined, including the measurement of the concept.

Activities of Daily Living↗

Factors affecting body tissue mobilization in early lactation dairy cows. 2. Effect of dietary fat on mobilization of body fat and protein.

Twenty-two multiparous Holstein cows were fed either a control diet or a control diet plus 3% added fat (dry matter basis) to determine the effect of added dietary fat on body tissue mobilization and milk production. Body composition measurements were taken using the D2O dilution technique at -2, 5, and 12 wk postpartum. Cows fed added fat produced 2.7 kg/d more milk than did those fed the control diet alone, but milk production, milk composition, and dry matter intake were not affected by diet. The maximum amount of body tissue loss occurred between -2 and 5 wk postpartum when cows fed both diets mobilized 46 kg of body fat and 12 kg of body protein. Between 5 and 12 wk postpartum, only small changes in both body protein and body fat were observed. Even though cows fed added fat showed a tendency toward reduced body fat mobilization (66 kg for cows fed the control diet vs. 37 kg for cows fed the control diet plus added fat) and increased body protein mobilization (4.8 kg for cows fed the control diet vs. 19.5 kg for cows fed the control diet plus added fat), the differences were not significant. Apparent differences in fat mobilization between diets might have been due to initial body fat stores (159 kg for cows fed the control diet vs. 126 kg for cows fed the control diet plus added fat). Across diets, one unit of change in body condition score corresponded to about 55 kg of empty body fat. Supplemental dietary fat did not reduce body tissue mobilization in early lactation.

Adipose Tissue↗

Assessment of tooth mobility using small loads. I. Technical devices and calculations of tooth mobility in periodontal health and disease.

An apparatus for recording tooth mobility of maxillary anterior teeth using loads below 100 p in a bucco-lingual direction is described. Strain gauges and a differential transformer are used as sensors of force and displacement. The displacement is recorded at the same location on the tooth surface and in the same direction as the loading force. Compressed air is used as the source of force. Documentation of signals is obtained by means of a two-channel potentiometric recorder. Tooth mobility was studied in six subjects with healthy periodontal conditions and in six subjects with moderate periodontal disease. Repeated measurements under standardized conditions demonstrated a satisfactory reproducibility of the measuring method. Tooth mobility curves within the 20-80 p loading range were transformed to lines of regression. Analysis of such lines seems to provide further information of tooth mobility qualities as compared to previous methods of tooth mobility measurements.

Dental Stress Analysis↗

Use of recombinant human growth hormone (rhGH) plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) for the mobilization and collection of CD34+ cells in poor mobilizers.

The activity of recombinant human growth hormone (rhGH) in enhancing CD34(+) cell mobilization elicited by chemotherapy plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) was evaluated in 16 hard-to-mobilize patients, that is, those achieving a peak of circulating CD34+ cells 10/microL or less, or a collection of CD34(+) cells equal to or less than 2 x 10(6)/kg. Patients who had failed a first mobilization attempt with chemotherapy plus rhG-CSF (5 microg/kg/d) were remobilized with chemotherapy plus rhG-CSF and rhGH (100 microg/kg/d). As compared with rhG-CSF, the combined rhGH/rhG-CSF treatment induced significantly higher (P < or =.05) median peak values for CD34(+) cells/microL (7 versus 29), colony-forming cells (CFCs)/mL (2154 versus 28,510), and long-term culture-initiating cells (LTC-ICs)/mL (25 versus 511). Following rhG-CSF and rhGH/rhG-CSF, the median yields of CD34(+) cells per leukapheresis were 1.1 x 10(6)/kg and 2.3 x 10(6)/kg (P < or =.008), respectively; the median total collections of CD34(+) cells were 1.1 x 10(6)/kg and 6 x 10(6)/kg (P < or =.008), respectively. No specific side effect could be ascribed to rhGH, except a transient hyperglycemia occurring in 2 patients. Reinfusion of rhGH/rhG-CSF-mobilized cells following myeloablative therapy resulted in prompt hematopoietic recovery. In conclusion, our data demonstrate that in poor mobilizers addition of rhGH to rhG-CSF allows the patients to efficiently mobilize and collect CD34(+) cells with maintained functional properties.

Adult↗

Ion mobility spectrometry and ion mobility spectrometry/mass spectrometric characterization of dimenhydrinate.

Positive and negative ion mobility spectra of dimenhydrinate are presented, and the calculated reduced mobility (K0) values for the most significant peaks are reported. Mass identification of the ionic species associated with the peaks in the ion mobility spectra was achieved by interfacing the ion mobility spectrometer to a mass spectrometer. The application of ion mobility spectrometry to the detection of dimenhydrinate and other drug residues on the hands of patients admitted to hospital with drug overdose is also discussed.

Dimenhydrinate↗

Mobilization of the non-conjugative plasmid RSF1010: a genetic and DNA sequence analysis of the mobilization region.

The entire region required for mobilization of the non-conjugative plasmid RSF1010 has been cloned into a mobilization-deficient pBR322 derivative. The segment of DNA cloned was approximately 1.8 kb and included the origin of conjugal DNA transfer (oriT). The DNA sequence of the mobilization region has been determined, and revealed the presence of several overlapping reading frames. The isolation and mapping of both Tn1725 and BamH1-linker insertions and comparison with the DNA sequence data has allowed the identification of three genes required for mobilization. Two of these genes are overlapping and encode proteins of 16 kDa and greater than 65 kDa (although the truncated protein is functional, the gene extends outside the region cloned). The third gene is transcribed in the opposite direction. Promoters capable of transcribing these genes were located by S1 mapping in the inter-cistronic region between these divergently transcribed genes. The oriT site is located in this region, and the transcriptional patterns observed for mob+ and mob- plasmids implied that the promoters may be regulated by two of the mobilization proteins binding to the oriT site.

Base Sequence↗

The mobile receptor hypothesis revisited: a mechanistic role for hormone receptor lateral mobility in signal transduction.

Recent application of the technique of fluorescence photobleaching recovery to direct measurement of the lateral mobility of plasma membrane-localized hormone receptors has shed new light on the role of receptor lateral mobility in signal transduction. Receptors for insulin and EGF have been known for some time to be largely immobile at physiological temperatures. This presumably relates to their signal transduction mechanism, which appears to require intermolecular autophosphorylation (receptor aggregation) for activation. In contrast, G-protein coupled receptors must interact with other membrane components to bring about signal transduction, and it is interesting in this regard that the adenylate cyclase (AC) activating vasopressin V2-receptor is highly laterally mobile at 37 degrees C. It has recently been possible to reversibly modulate the V2-receptor mobile fraction (f) to largely varying extents, and to demonstrate thereby a direct effect on the maximal rate of in vivo cAMP production at 37 degrees C in response to vasopressin. A direct correlation between f and maximal cAMP production indicates that f may be a key parameter in hormone signal transduction in vivo, especially at sub-KD (physiological) hormone concentrations, with mobile receptors being required to effect G-protein activation.

Adenylyl Cyclases↗