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Mobility of people with lower limb amputations: scales and questionnaires: a review.

OBJECTIVE AND DESIGN: A systematic literature review to compare mobility scales used for lower limb amputees. A literature search was carried out by computerized search of biomedical literature including Medline and Embase. The studies included were published between 1978 and 1998 and including the following keywords: amputation, artificial limbs, prosthesis, lower limb, activities of daily living, mobility. RESULTS: Thirty-five studies were identified; 19 had a measurement of separate levels of mobility comparable to each other. Sixteen studies used ordinal and ratio scales without separate levels of mobility. The widest range of measurement found was the scale from 'walking with prosthesis without a walking aid' to 'totally confined to bed'. The Stanmore Harold Wood mobility scale was published most frequently. None of the 35 studies presented give a continuous measurement of mobility. CONCLUSION: A multitude of measurement scales and questionnaires are available for differ in methods and measuring range. Measuring mobility by a scale has been shown to have limitations. Several authors did extensive research but they all measure only a number of aspects of mobility. Consensus about the measurement of mobility of lower limb amputees is not available in the recent literature.

Activities of Daily Living↗

The use of water structure breakers, urea and guanidium chloride, new mobile phase modifiers in reversed-phase partition high-performance liquid chromatography.

Organic solvent-free mobile-phase systems in ion-pair reversed-phase partition high-performance liquid chromatography (IPRP-HPLC) are demonstrated; using urea at 3.0-7.0 molal (mol kg-1) as a modifier in a mobile phase on an octadecylsilanized silica column, four nitrophenolates and metal 4-(2-pyridilazo)resorcinol (PAR) chelates (in PAR chelates system an aqueous mobile phase with 15 wt% methanol was used) were separated rapidly within 6 min at no sacrifice to the separation efficiency. On the addition of urea in the mobile phase, reduced retention times of nitrophenolates and naphthalenesulfonates and also diminution of the height equivalent to a theoretical plate were observed. The addition of urea and guanidium chloride (GuCl) in the mobile phase gave rise to a decrease in the mobile phase volume; in turn, this meant an increased volume of the stationary phase. As the concentration of urea and GuCl in the mobile phase increased, the volume of the mobile phase in the column decreased within about 70% and 40% at 7.0 molal of urea and GuCl, respectively. A decrease in the mobile phase volume suggests an increase in the extent of solvation of the bonded hydrocarbon chain of the stationary phase. The possible explanations for the LC behavior with the urea and GuCl are turned into reduction of hydrophobic interaction in LC processes, solute partitioning and entangling of alkyl chain brushes, with the addition of urea. The water structure breakers, urea and GuCl, most likely affect the solvation states of both solute molecules and the hydrocarboneous stationary phase by changing the nature of the water solvent, which provides a new technique for fine tuning of the LC resolution of the analytes.

Anions↗

Dorsal first ray mobility in women athletes with a history of stress fracture of the second or third metatarsal.

STUDY DESIGN: Retrospective case-control study. OBJECTIVE: To examine the amount of dorsal first ray mobility in subjects having a history of stress fracture of the second or third metatarsal as compared to control subjects, and to test the influence of navicular drop, length of the first ray, and generalized joint laxity on the measure of dorsal mobility. BACKGROUND: [corrected] Instability of the first ray may cause the lesser metatarsals to carry greater weight and contribute to the incidence of metatarsal stress fracture. Stability of the first ray is believed to be compromised when subtalar joint pronation continues into late stance, the first metatarsal is short, or an individual has generalized joint laxity. To date, no research has assessed the relationship of these etiological factors to the measure of first ray mobility. METHODS AND MEASURES: Fifteen women athletes having a history of a second or third metatarsal stress fracture were matched by age, body mass, and sport activity to women athletes without fracture. Dorsal first ray mobility was quantified by a device using a standard load of 55 N. Change in vertical height of the navicular during stance was the measure of foot pronation. Relative length of the first ray navicular segment compared to the length of the second ray navicular segment was measured by caliper. Generalized joint laxity was evaluated using the Beighton 9-point scale. Within-day repeated measures assessed reliability. Differences between groups were determined by independent t test. Multiple polynomial regression analysis assessed the relationship between dorsal mobility and navicular drop, length of the first ray, and joint laxity. RESULTS: Interrater reliability coefficients ranged from 0.36 for metatarsal length to 0.71 for navicular drop. The intrarater reliability coefficient for dorsal first ray mobility was 0.93. Dorsal first ray mobility was not significantly different between the 2 groups. With regression analysis, the Beighton score was the only variable retained as a significant predictor of dorsal mobility (R2 = 0.24). CONCLUSION: Results do not support the theory that describes the unstable first ray as a common cause of metatarsal stress fracture. In addition, this investigation found generalized joint laxity to be a significant predictor of dorsal first ray mobility.

Adolescent↗

Evaluation of a mobile computerized grain feeder for lactating cows grazing grass pasture.

The objective of this study was to evaluate a mobile computerized grain feeder for use to feed individually Holstein cows grazing grass pasture. Thirty-two Holstein cows averaging 95 d of lactation and 39.3 kg/d of milk were rotationally grazed on predominantly Dactylis glomerata pastures for 9 wk starting in early May. Cows were blocked according to parity, days of lactation, and milk yield. Cows were randomly assigned to a control group in which cows were individually fed grain twice daily at milking or to a group that was offered grain four times daily using a mobile grain feeder in the pasture. Cows in both groups were offered 1 kg of grain/3 kg of milk; pasture was the only source of forage. Cows fed using the mobile grain feeder consumed less grain than did control cows (9.3 vs. 11.3 kg/d) and tended to yield less milk, but with a higher fat content. A separate analysis was conducted using data from only those cows that were fed using the mobile grain feeder and that consumed, in four relatively equal amounts, at least 75% of the allotted grain of their respective pairmates (7 per group) in the control group. When cows that were using the mobile grain feeder consumed amounts of grain comparable with that of the controls, more frequent grain feeding did not alter milk yield or composition. Plasma samples (five per cow per treatment) were collected at 2-wk intervals to measure glucose, urea N, and nonesterified fatty acids (NEFA). Plasma glucose and urea N were not affected by treatment and averaged 54.9 and 19.9 mg/ dl for all cows, respectively. Cows fed grain using the mobile feeder had higher (212.4 vs. 170.5 meq/L) concentrations of NEFA than did control cows, but, when cows consumed greater than 75% of their allotted grain from the mobile feeder, concentrations of NEFA were similar. The mobile grain feeder can be used to feed cows individually on pasture; however, adaptation of the cows to the mobile grain feeder appears to be important.

Animal Feed↗

Effect of physical therapy on limited joint mobility in the diabetic foot. A pilot study.

Eleven patients with limited joint mobility and neuropathy were enrolled in a physical therapy program of passive joint mobilization at a rate of two sessions per week. Treatment resulted in a significant improvement in joint mobility after 10 sessions. Further improvement after 20 sessions did not reach the level of statistical significance, although near-normal joint mobility was attained. After completion of therapy, there was a progressive deterioration in joint mobility. No serious adverse effects were noted during treatment. This study provides some evidence that use of physical therapy may result in significant, although temporary, improvement in the mobility of the ankle and foot joints in diabetic patients with limited joint mobility and neuropathy. As limited joint mobility has been associated with the development of abnormally high pressures under the feet, which in turn may contribute to plantar ulceration in the susceptible neuropathic foot, the results indicate that physical therapy may be useful in the prevention of plantar ulceration in diabetic patients with limited joint mobility and neuropathy, although this must be verified by additional research.

Adult↗

Perceived visual ability for independent mobility in persons with retinitis pigmentosa.

PURPOSE: To determine the distribution of perceived ability for independent mobility in people who are at various stages of retinitis pigmentosa (RP). METHODS: A questionnaire was developed to ask subjects to rate how difficult they found each of 35 mobility situations if they had no assistance. The scale was 1 (no difficulty) to 5 (extreme difficulty). In each of 127 subjects, the Rasch analysis, a latent trait analysis, was used to convert the ordinal difficulty ratings into interval measures of perceived visual ability for independent mobility. RESULTS: Content validity of the questionnaire was shown by good separation indexes (4.55 and 8.0) and high reliability scores (0.96 and 0.98) for the person and the item parameters. Construct validity was shown with model fit statistics. Criterion validity of the questionnaire was shown by good discrimination among mobility-related behavior such as "limit independent travel," "always ask for accompaniment," "use a mobility aid," and "have a fear of falling." The mobility situation shown to require the least visual ability was "moving about in the home"; the situation requiring the most was "walking at night." Bivariate regression analysis determined that for every decade of disease progression, perceived visual ability for mobility decreased by approximately 0.5 logit, which was slightly less than 10% of the total range in the study sample. A linear combination of the visual function measures, log minimum angle of resolution, log contrast sensitivity, and log retinal area accounted for 57% of the variability in the person measure. CONCLUSIONS: The patient-based assessment, developed to determine difficulty across a range of mobility situations, is a valid way to measure perceived ability for independent mobility. This latent trait varies systematically with the progression of RP and with visual function measures.

Activities of Daily Living↗

Granulocyte colony-stimulating factor-mobilized allogeneic stem cell transplantation maintains graft-versus-leukemia effects through a perforin-dependent pathway while preventing graft-versus-host disease.

Minimization of graft-versus-host disease (GVHD) with preservation of the graft-versus-leukemia (GVL) effect is a crucial step to improve the overall survival of allogeneic bone marrow transplantation (BMT) for patients with hematological malignancies. We and other investigators have shown that granulocyte colony-stimulating factor (G-CSF)-mobilized allogeneic peripheral stem cell transplantation (PBSCT) reduces the severity of acute GVHD in murine models. In this study, we investigated whether G-CSF-mobilized PBSC maintain their GVL effect in a murine allogeneic transplant model (B6 --> B6D2F1). B6 mice (H-2(b)) were injected subcutaneously with human G-CSF (100 micrograms/kg/d) for 6 days and their splenocytes were harvested on day 7 as a source of PBSC. G-CSF mobilization dramatically improved transplant survival compared with nonmobilized controls (95% v 0%, P <.001). Systemic levels of lipopolysaccharide and tumor necrosis factor-alpha were markedly reduced in recipients of allogeneic G-CSF-mobilized donors, but cytolytic T lymphocyte (CTL) activity against host tumor target cells p815 was retained in those recipients. When leukemia was induced in recipients by coinjection of p815 tumor cells (H-2(d)) at the time of transplantation, all surviving recipients of G-CSF-mobilized B6 donors were leukemia-free at day 70 after transplant, whereas all mice who received T-cell-depleted (TCD) splenocytes from G-CSF-mobilized B6 donors died of leukemia. When splenocytes from G-CSF-mobilized perforin-deficient (pfp-/-) mice were used for transplantation, 90% of recipients died of leukemia, demonstrating that perforin is a crucial pathway mediating GVL effects after G-CSF-mobilized PBSCT. These data illustrate that G-CSF-mobilized allogeneic PBSCT separate GVL from GVHD by preserving perforin-dependent donor CTL activity while reducing systemic inflammation.

Animals↗

Factors affecting blood stem cell collections following high-dose cyclophosphamide mobilization in lymphoma, myeloma and solid tumors.

Sixty patients with malignancy were enrolled in a study of high-dose chemotherapy and peripheral blood stem cell transplantation (PBSCT). Stem cells were harvested prior to PBSCT using high-dose cyclophosphamide (CY) mobilization (4 or 7 g/m2) with collection of a median of 4.6 x 10(8)/kg mononuclear cells (range 0.2-9.5) and 21.6 x 10(4)/kg colony forming unit-granulocyte/macrophage (CFU-GM) (range 0.1-220). Forty-seven patients were mobilized once, 11 required two cycles and two required three cycles. Eight patients (13%) failed to reach the optimum CFU-GM target (greater than 15 x 10(4)/kg) following CY mobilization. A number of factors identified those patients who were likely to achieve optimum CFU-GM collections with CY mobilization. These included the use of the higher CY mobilization dose, a longer interval from last chemotherapy cycle to mobilization, and a higher premobilization bone marrow CFU-GM level. Patient's age, the degree of bone marrow infiltration, the nature of disease or the number of pre-mobilization chemotherapeutic cycles did not affect the ability to collect optimum CFU-GM numbers. Whilst the mobilization procedure was associated with moderate non-hematologic toxicity, significant hematological morbidity was observed primarily in patients mobilized using the 7 g/m2 dose. Refinements to the protocol, in particular the use of hematopoietic growth factors, are currently under investigation.

Adolescent↗

[Correlation between urethral mobility and maximal urethral closure pressure and Valsalva leak-point pressure in women with urinary stress incontinence].

OBJECTIVE: The aim of our study was to examine the relationship between urethral mobility in females and maximum urethral closure pressure (MUCP) at rest, and between urethral mobility and Valsalva leakpoint pressure (VLPP), and to determine whether urethral mobility correlates with MUCP and VLPP. DESIGN: Cross-sectional clinical study. SETTINGS: Gynecological and Obstetric Clinic, First School of Medicine of Charles University and General Faculty Hospital, Prague. MATERIALS AND METHODS: Fifty-two women with previously untreated GSI were recruited to participate in a clinical study. Their mean age was 57.2, mean body mass index (BMI) 28, and mean parity 1.8. As part of the urethral pressure profile we determined MUCP and functional urethral length (FUL). VLPP was assessed during US examination using an ultrasound contrast medium and color Doppler velocimetry (CDV). A perineal ultrasound examination in patients in supine position (by Acuson 128 XP 10, curved array probe 5 MHz) to assess the position of UVJ and the middle of the urethra was performed. The bladder was filled with 300 ml sterile saline. RESULTS: We did not find statistically significant differences in the mobility of urethrovesical junction (UVJ) and middle of the urethra between patients with low or normal VLPP at 5% level. On the other hand, we found statistically significant correlation in the mobility of urethrovesical junction (UVJ) and middle of the urethra with MUCP, where these parameters were assessed as mutually dependent values. However, if we set the borderline of UVJ hypermobility at 50 degrees or more (the difference in the value of gamma angle at maximum Valsalva maneuvre and at rest), and a low MUCP at equal to or less than 30 cm H2O, then we do not observe any correlation between the values of urethral mobility and MUCP, since combinations of these two values are too extreme. CONCLUSIONS: This study mainly compares three parameters--the urethral mobility with MUCP and with VLPP. Based on our results we can conclude that there is no statistically significant correlation between hypermobility of the urethra and VLPP at 5% level. However, we did find a statistically significant correlation between MUCP and mobility of UVJ and middle of the urethra if the values for these parameters are not strictly assessed. If we set the borderline of UVJ hypermobility at 50 degrees or more and a low MUCP at equal to or less than 30 cm H2O, then we do not observe any correlation between the values of urethral mobility and MUCP.

Adult↗

[Changes in urethra mobility after TVT operation].

OBJECTIVE: The aim of our study was to asses changes in the mobility of the whole urethra after successful TVT procedure. DESIGN: Prospective pilot study. SETTING: Obstet. Gynecol Department, General Teaching Hospital, 1st Medical Faculty, Charles University, Prague; EuroMISE Centre of the Charles University and Academy of Sciences, Prague, Czech Republic. METHODS: 101 women with proven stressed urinary incontinence were included in the study. After the TVT procedure 90 women were evaluated. As a part of the complex urogynecological investigation before surgery the transperineal ultrasound scan was performed in supine position, urinary bladder was filled to 300 ml. In the orthogonal system of coordinates the position and mobility of the whole urethra before surgery were assessed. Control examination was done 3-6 months after the surgery. The changes induced by the surgery were assessed. For the statistical evaluation t-test, Wilcox test, F test, Kruskal-Wallis test and ANOVA were used. RESULTS: Surgery significantly decreased the mobility of the whole parts of the urethra during maximal Valsalva, but the position at rest is not influenced. The women with high urethral mobility have high mobility after the surgery. The operation was more effect in patients with high mobility. Never the less the change of relative mobility is the same in all women. CONCLUSIONS: The information about the type of urethral mobility is important and may increase the success rate of TVT. Therefore the tension of the tape should be different for patients with different urethral mobility.

Female↗

[The impact of rhG-CSF mobilization on migration and adhesive function of CD4+ T cells].

OBJECTIVE: To explore the impact of mobilization with recombinant human granulocyte colony stimulated factor (rhG-CSF) on the migration and adhesive function and their related signal mechanism mediated by the CXCR4 and lymphocyte function antigen-1 (LFA-1) molecules on the surfaces of CD4(+) T cells. METHODS: Before and at day 5 on rhG-CSF mobilization, the expression rates of CXCR4 and LFA-1 (CD11a) on CD4(+) T cells in the peripheral blood were detected by tricolor fluorescence labeling, and the migration and adhesive activities of CD4(+) T cells to stroma cell-derived factor 1 alpha (SDF-1 alpha) and intercellular adhesion molecule-1 (ICAM-1) were also tested. RESULTS: The expression of CXCR4 on CD4(+) T lymphocytes was (84.58 +/- 20.31)% before mobilization and (81.23 +/- 22.46)% at day 5 on mobilization. The expression of LFA-1 on CD4(+) T lymphocytes before and at day 5 on mobilization was 100%. There was no significant difference in the expression CXCR-4 and LFA-1 on CD4(+) T lymphocytes whether mobilization (P > 0.05). SDF-1 alpha induced 4 hours' CD4(+) T cells migration didn't change markedly before and after mobilization \[(28.5 +/- 10.3)% vs (31.2 +/- 8.9)%\] (P > 0.05). The adhesive activity of CD4(+) T cells to ICAM-1 was decreased from (85.59 +/- 14.21)% to (61.45 +/- 15.07)% after mobilization (P < 0.05). CONCLUSIONS: The expression of CXCR4 and LFA-1 on CD4(+) T lymphocytes didn't change markedly during rhG-CSF mobilization, but the adhesive activity of CD4(+) T cells to ICAM-1 was frustrated after that.

CD4-Positive T-Lymphocytes↗

Studies on the hepatic calcium-mobilizing activity of aluminum fluoride and glucagon. Modulation by cAMP and phorbol myristate acetate.

The effects of submaximal doses of AlF4- to mobilize hepatocyte Ca2+ were potentiated by glucagon (0.1-1 nM) and 8-p-chlorophenylthio-cAMP. A similar potentiation by glucagon of submaximal doses of vasopressin, angiotensin II, and alpha 1-adrenergic agonists has been previously shown (Morgan, N. G., Charest, R., Blackmore, P. F., and Exton, J. H. (1984) Proc. Natl. Acad. Sci. U. S. A. 81, 4208-4212). When hepatocytes were pretreated with the protein kinase C activator 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA), the effects of AlF4- to mobilize Ca2+, increase myo-inositol 1,4,5-trisphosphate (IP3), and activate phosphorylase were attenuated. Treatment of hepatocytes with PMA likewise inhibits the ability of vasopressin, angiotensin II, and alpha 1-adrenergic agonists to increase IP3 and mobilize Ca2+ (Lynch, C. J., Charest, R., Bocckino, S. B., Exton, J. H., and Blackmore, P. F. (1985) J. Biol. Chem. 260, 2844-2851). In contrast, the ability of AlF4- or angiotensin II to lower cAMP or inhibit glucagon-mediated increases in cAMP was unaffected by PMA. The ability of AlF4- to lower cAMP was attenuated in hepatocytes from animals treated with islet-activating protein, whereas Ca2+ mobilization was not modified. These results suggest that the lowering of cAMP induced by AlF4- and angiotensin II was mediated by the inhibitory guanine nucleotide-binding regulatory protein of adenylate cyclase, whereas Ca2+ mobilization was not. Addition of glucagon, forskolin, or 8CPT-cAMP to hepatocytes raised IP3 and mobilized Ca2+. Both effects were blocked by PMA pretreatment, whereas cAMP and phosphorylase a levels were only minimally affected by PMA. The mobilization of Ca2+ induced by cAMP in hepatocytes incubated in low Ca2+ media was not additive with that induced by maximally effective doses of vasopressin, angiotensin II, or alpha 1-adrenergic agonists, indicating that the Ca2+ pool(s) affected by agents which increase cAMP is the same as that affected by Ca2+-mobilizing hormones which do not increase cAMP. These findings support the proposal that AlF4- mimics the effects of the Ca2+-mobilizing hormones in hepatocytes by activating a guanine nucleotide-binding regulatory protein (Np) which couples the hormone receptors to a phosphatidylinositol 4,5-bisphosphate (PIP2)-specific phosphodiesterase. They also suggest that Np, PIP2 phosphodiesterase, or a factor involved in their interaction is activated following phosphorylation by cAMP-dependent protein kinase and inhibited after phosphorylation by protein kinase C.(ABSTRACT TRUNCATED AT 400 WORDS)

1-Methyl-3-isobutylxanthine↗

An equation for DNA electrophoretic mobility in agarose gels.

Assignment of molecular weight to DNA fragments on the basis of electrophoretic mobility in agarose gels is complicated by nonlinearity of the relationship between mobility and molecular weight. Graphical methods that linearize sigmoidal curves provide a simplified description of the mobility function when applied to normalized mobility data. This description is valid over a wide range of molecular weights. Linear duplex molecules of lengths ranging from 118 to 169,200 base pairs were electrophoresed at voltage gradients of 1 to 6 V/cm through horizontal slab gels ranging from 0.2 to 1.6% agarose. A logit transformation of the mobility graphed versus the logarithm of molecular weight, analogous to a Hill plot of enzyme kinetics, is a straight line. Changes in the voltage gradient or gel composition alter the position but not the slope or linearity of the data plotted by this method. The logistic representation is compared with the conventional graph of log molecular weight versus mobility, with the graph of molecular weight versus reciprocal mobility, and with Probit analysis of the mobility function. Parameters were determined for one equation that accurately describes DNA mobility as a function of the three tested variables. Curves are presented that are useful in predicting fragment length, migration, resolution, and gel performance.

DNA, Viral↗

Phosphorylation-induced mobility shift in phospholamban in sodium dodecyl sulfate-polyacrylamide gels. Evidence for a protein structure consisting of multiple identical phosphorylatable subunits.

Phosphorylation of purified phospholamban isolated from canine cardiac sarcoplasmic reticulum vesicles decreased the electrophoretic mobility of the protein in sodium dodecyl sulfate (SDS)-polyacrylamide gels. Different mobility forms of phospholamban in SDS gels were visualized both by direct protein staining and by autoradiography. Unphosphorylated phospholamban migrated with an apparent Mr = 25,000 in SDS gels; maximal phosphorylation of phospholamban by cAMP- or Ca2+-calmodulin-dependent protein kinase increased the apparent Mr to 27,000. Partial phosphorylation of phospholamban by either protein kinase gave intermediate mobility forms of molecular weights between 25,000 and 27,000, suggesting that more than one phosphorylation site was present on the holoprotein for each activity. Boiling of phospholamban in SDS dissociated the holoprotein into an apparently homogeneous class of low molecular weight "monomers." Only two mobility forms of monomeric phospholamban were observed in SDS gels after phosphorylation by cAMP-dependent protein kinase, corresponding to 9-kDa dephospho- and 11-kDa phosphoproteins. All of the 9-kDa protein could be phosphorylated and converted into the 11-kDa mobility form, suggesting the presence of only one site of phosphorylation on a single type of monomer for cAMP-dependent protein kinase. Simultaneous phosphorylation of monomeric phospholamban by cAMP-dependent protein kinase and Ca2+-calmodulin-dependent protein kinase gave an additional mobility form of the protein, suggesting that different sites of phosphorylation were present for each activity on each monomer. Incomplete dissociation of the holoprotein by boiling it in a relatively low concentration of SDS facilitated the detection of five major mobility forms of the protein in SDS gels, and the mobilities of all of these forms were decreased by phosphorylation. We propose that the high molecular weight form of phospholamban is a multimer of electrophoretically indistinguishable monomers, each of which contains a different phosphorylation site for cAMP-dependent protein kinase activity and Ca2+-calmodulin-dependent protein kinase activity. Phosphorylation of phospholamban at multiple sites is responsible for the various mobility forms of the holoprotein detected in SDS-polyacrylamide gels.

Adenosine Triphosphatases↗

Rapid engraftment by peripheral blood progenitor cells mobilized by recombinant human stem cell factor and recombinant human granulocyte colony-stimulating factor in nonhuman primates.

We have previously shown that administration of low-dose recombinant human stem cell factor (rhSCF) plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) to baboons mobilizes greater numbers of progenitor cells in the blood than does administration of rhG-CSF alone. The purpose of the present study was to determine whether marrow repopulating cells are present in the blood of nonhuman primates administered low-dose rhSCF plus rhG-CSF, and if present, whether these cells engraft lethally irradiated recipients as rapidly as blood cells mobilized by treatment with rhG-CSF alone. One group of baboons was administered low-dose rhSCF (25 micrograms/kg/d) plus rhG-CSF (100 micrograms/kg/d) while a second group received rhG-CSF alone (100 micrograms/kg/d). Each animal underwent a single 2-hour leukapheresis occurring the day when the number of progenitor cells per volume of blood was maximal. For baboons administered low-dose rhSCF plus rhG-CSF, the leukapheresis products contained 1.8-fold more mononuclear cells and 14.0-fold more progenitor cells compared to the leukapheresis products from animals treated with rhG-CSF alone. All animals successfully engrafted after transplantation of cryopreserved autologous blood cells. In animals transplanted with low-dose rhSCF plus rhG-CSF mobilized blood cells, we observed a time to a platelet count of > 20,000 was 8 days +/- 0, to a white blood cell count (WBC) of > 1,000 was 11 +/- 1 days, and to an absolute neutrophil count (ANC) of > 500 was 12 +/- 1 days. These results compared with 42 +/- 12, 16 +/- 1, and 24 +/- 4 days to achieve platelets > 20,000, WBC > 1,000, and ANC > 500, respectively, for baboons transplanted with rhG-CSF mobilized blood cells. Animals transplanted with low-dose rhSCF plus rhG-CSF mobilized blood cells had blood counts equivalent to pretransplant values within 3 weeks after transplant. The results suggest that the combination of low-dose rhSCF plus rhG-CSF mobilizes greater numbers of progenitor cells that can be collected by leukapheresis than does rhG-CSF alone, that blood cells mobilized by low-dose rhSCF plus rhG-CSF contain marrow repopulating cells, and finally that using a single 2-hour leukapheresis to collect cells, the blood cells mobilized by low-dose rhSCF plus rhG-CSF engraft lethally irradiated recipients more rapidly than do blood cells mobilized by rhG-CSF alone.

Animals↗

The mobilization of primitive hemopoietic progenitors into the peripheral blood.

There is considerable interest in the use of peripheral blood progenitor cells (PBPC) for hemopoietic rescue following high dose chemotherapy. Current regimens mobilize CD34+ with variable efficacy and there remains considerable empiricism in the design of these regimens. Some involve myelosuppression, some the administration of various cytokines alone or in combination, while a combination of chemotherapy and cytokines is employed in others. Certain protocols result in mobilization within one week while in others, maximal PBPC levels occur only after several weeks. Thus, procedures required for optimal mobilization of PBPC remain to be defined. An understanding of the mechanisms responsible for mobilization may lead to the development of improved mobilization strategies. Herein we review data that explore the mechanisms involved in the mobilization of PBPC in man. These data demonstrate that mobilization is associated with marked changes in the expression and function of cell adhesion molecules (CAMs) on hemopoietic progenitor cells (HPC), suggesting that the release of HPC into the blood involves a perturbation of the adhesive interactions between these cells and the marrow stroma that, in steady-state conditions, serve to restrict HPC to the bone marrow. Downregulation of c-kit is invariably associated with successful mobilization which, when combined with data from in vitro studies, implies a key role for stem cell factor (SCF) as an orchestrator of mobilization.

Animals↗

[Experimental study on the effects of tension-reduced early mobilization on extensor tendon healing].

Numerous clinical and experimental studies have been reported on early postoperative mobilization after flexor tendon repair. However, there have been only a few experimental studies reported on extensor tendon repair. In 1989, Ishiguro reported the usefulness of tension-reduced early mobilization in clinical cases of extensor tendon ruptures. The purpose of this experimental study was to examine the in vivo effect of tension-reduced early mobilization on extensor tendon healing in chicken. An experiment was performed on the extensor tendons of 218 chickens in an attempt to examine the effects of tension-reduced early mobilization on tendon healing and adhesion. The extensor tendon of the fourth toe was cut and the distal stump of the tendon was transferred to the extensor tendon of the third toe. Postoperatively two protocols were employed. In the immobilization group, a cast was applied for three weeks. In the early-mobilization group, immediate active motion of the digits was allowed. A tension-reduced position was maintained by taping the fourth toe to the dorsum of the third. The findings from the early mobilization group and from the immobilization group were as follows: 1. Macroscopically, sutures at the repair site of the early-mobilized tendon were not evident after three weeks because of fibrous connective tissue growth. Despite this abundant connective tissue, tendon gliding was observed to be smooth. Between the suture site and the gliding floor, loose connective tissue, similar to normal paratenon, was observed. Histology confirmed this observation. 2. The tensile strength required to extend the MP joint was significantly lower for the early-mobilization group than for the immobilization group, suggesting minimal adhesion between the sutured tendon and the gliding floor in the early-mobilization group. 3. No significant difference in tensile strength among the various tendon repair techniques employed was observed at the suture site.

Animals↗

Primitive long-term culture initiating cells (LTC-ICs) in granulocyte colony-stimulating factor mobilized peripheral blood progenitor cells have similar potential for ex vivo expansion as primitive LTC-ICs in steady state bone marrow.

We have recently shown that more than 90% of long-term culture initiating cells (LTC-IC) mobilized in the peripheral blood (PB) of normal individuals express HLA-DR and CD38 antigens and can sustain hematopoiesis for only 5 weeks. However, 10% of LTC-IC in mobilized PB are CD34+ HLA-DR- and CD34+ CD38- and can sustain hematopoiesis for at least 8 weeks. We now examine the ex vivo expansion potential of CD34+ HLA-DR+ cells (rich in mature LTC-IC) and CD34+ HLA-DR- cells (rich in primitive LTC-IC) in granulocyte colony-stimulating factor (G-CSF) mobilized PB progenitor cells (PBPC). Cells were cultured in contact with M2-10B4 cells (contact) or in transwells above M2-10B4 (noncontact) without and with interleukin-3 (IL-3) and macrophage inflammatory protein (MIP-1alpha) for 2 and 5 weeks. Progeny were evaluated for the presence of colony-forming cells (CFC) and LTC-IC. When CD34+ HLA-DR+ PB cells were cultured in contact cultures without cytokines, a threefold expansion of CFC was seen at 2 weeks, but an 80% decrease in CFC was seen at week 5. Further, the recovery of LTC-IC at week 2 was only 17% and 1% at week 5. This confirms our previous observation that although CD34+ HLA-DR+ mobilized PB cells can initiate long-term cultures, they are relatively mature and cannot sustain long-term hematopoiesis. In contrast, when CD34+ HLA-DR- mobilized PB cells were cultured in contact cultures without cytokines, CFC expansion persisted until week 5 and 49% and 11% of LTC-IC were recovered at week 2 and 5, respectively. As we have shown for steady state bone marrow (BM) progenitors, recovery of LTC-IC was threefold higher when CD34+ HLA-DR- PBPC were cultured in noncontact rather than contact cultures, and improved further when IL-3 and MIP-1alpha were added to noncontact cultures (96 +/- 2% maintained at week 5). We conclude that although G-CSF mobilizes a large population of "mature" CD34+ HLA-DR+ LTC-IC with a limited proliferative capacity, primitive CD34+ HLA-DR- LTC-IC present in mobilized PB have similar characteristics as LTC-IC from steady state BM: (1) they can be maintained in noncontact cultures containing IL-3 and MIP-1alpha for at least 5 weeks; (2) they are subject to the same proliferation inhibitory influences of contact with stroma. Since the absolute number of primitive LTC-IC (week 8 LTC-IC) per mL of G-CSF mobilized PB is similar to that per mL of steady state BM, these studies further confirm that G-CSF mobilized PBPC may have similar long-term repopulating abilities as steady state BM.

Antigens, CD34↗