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991.
Calvin J. Rushing Viraj R. Rathnayake Adam J. Oxios Gabriel P. Galan Madelin Ramil Steven M. Spinner Patrick Hardigan 《The Journal of foot and ankle surgery》2018,57(6):1080-1086
In some chronic musculoskeletal conditions, patients with persistent pain and disability have still achieved recovery through behavioral adaptations (readjustment) or cognitive coping (redefinition). Although the pendulum shift from physician-reported clinical indicators to patient-reported outcomes measures (PROMs) has recently focused on quantifying residual pain and disability to determine recovery (resolution), whether patients are capable of coping with any ongoing deficits and achieving other forms of recovery has not been considered. We performed a retrospective case series to assess patient-perceived recovery and outcomes after silastic implant arthroplasty for hallux rigidus. From July 2006 to July 2016, 28 patients at a single institution were enrolled. PROMs were prospectively obtained and compared between patients considering themselves recovered without or with residual deficits (recovered-resolved, recovered-not resolved) and those not recovered. Holistic satisfaction, procedure-specific satisfaction, complications, reoperations, and failure rates were recorded. Overall, 50.0% perceived themselves as recovered-resolved, 43% as recovered-not resolved, and 7% as not recovered. The mean modified Foot Function Index was 17.26, the verbal analog scale for pain score was 2.03, and implant survivorship 100% at a median of 67 (interquartile range 28.4 to 103.5) months. Although only 50% of patients reported complete symptom resolution, satisfaction was high, and most perceived themselves as recovered, suggesting recovery in hallux rigidus might not always be predicated by the complete resolution of all symptomatology. Although PROMs relying on pain inference and functional disability will continue to be utilized with increasing frequency, foot and ankle surgeons should be cognizant of their inherent limitations in assessing other forms of recovery. 相似文献
992.
993.
Primary bone marrow blasts from 4 children with t(8;21) acute myeloid leukemia (AML), 6 children with inv(16) AML, and 2 children with t(9;11) AML were injected intravenously or transplanted under the kidney capsule of sublethally irradiated mice with severe combined immunodeficiency (SCID). Leukemic cells from all AML patients infiltrated the SCID mouse thymus, suggesting that the thymic microenvironment supports the survival and growth of human AML blasts. Blasts from 1 of 4 t(8;21) AML patients and 4 of 6 inv(16) AML patients caused histopathologically detectable disseminated leukemia. Blasts from the remaining patients produced disseminated occult leukemia that was only detected by polymerase chain reaction. Occurrence of histopathologically detectable disseminated leukemia was dependent on intravenous injection of leukemic cells; none of the mice challenged with an inoculum transplanted under the kidney capsule developed overt leukemia. No obvious association was noted between occurrence of leukemia in SCID mice and clinical or laboratory features presented by patients, including age, sex, or leukocyte count at diagnosis. To our knowledge, this study is the first to show that leukemic blasts from children with newly diagnosed AML, especially inv(16) AML, can cause disseminated human leukemia in SCID mice without exogenous cytokine support. The SCID mouse model system may prove particularly useful for designing more effective treatment strategies against childhood AML. 相似文献
994.
Identification of yeast artificial chromosomes containing the inversion 16 p-arm breakpoint associated with acute myelomonocytic leukemia 总被引:1,自引:1,他引:1
Liu P; Claxton DF; Marlton P; Hajra A; Siciliano J; Freedman M; Chandrasekharappa SC; Yanagisawa K; Stallings RL; Collins FS 《Blood》1993,82(3):716-721
We report the cloning of the chromosome 16 p-arm breakpoint involved in inversion 16(p13;q22) associated with subtype of acute myelomonocytic leukemia (AMML) M4Eo. Inter-Alu polymerase chain reaction (PCR) products from a series of interspecific somatic cell hybrids that contain only small portions of the human chromosome 16 p-arm were generated for use as fluorescent in-situ hybridization (FISH) probes. When applied to patient cells, rapid and unambiguous identification of the inversion resulted. Using FISH analysis, cosmid clones associated with the hybrids were identified that bracketed the p-arm breakpoint. A repeat-free fragment of one of these cosmids (35B11) when used as probe on Southern blots from pulsed-field gels identified rearranged macrorestriction fragments in patient DNA. Yeast artificial chromosomes (YACs) were isolated using sequences derived from cosmids flanking 35B11 in a cosmid contig. Of 4 YACs so identified, 3 were shown by FISH to cross the inversion-16 p-arm breakpoint. Therefore, the breakpoint has been molecularly cloned, and identified as being within these 3 YACs. These clones will facilitate the unraveling of the genetic events associated with inversion-16 and are available tools with immediate clinical application. 相似文献
995.
Combinations of recombinant colony-stimulating factors are required for optimal hematopoietic differentiation in serum-deprived culture 总被引:5,自引:1,他引:5
Previous in vitro investigations on enriched human hematopoietic progenitors have led to the conclusion that the purified recombinant multipoietins, interleukin 3 (IL-3) and granulocyte-macrophage colony- stimulating factor (GM-CSF) can alone induce the formation of colonies from a variety of multipotent and lineage committed progenitors. Since fetal calf serum was included in these cultures and itself might contain growth factors or other cofactors, we re-examined the actions of the CSFs in serum-deprived conditions. Results show that both the multipoietins are inadequate stimuli of colony formation. At maximal concentrations IL-3 alone induces only 25% of the granulocyte and macrophage colony-forming units (CFU-G and CFU-M) produced by a T-cell conditioned medium that contains a mixture of CSFs. When IL-3 was added at the initiation of the cultures and erythropoietin (ep), G-CSF, or M- CSF added on day 3, almost full recovery of erythroid, granulocytic, and monocytic colonies, respectively, was obtained. Similar results were obtained with GM-CSF except that fewer erythroid colonies were recovered at high concentrations, and almost maximal CFU-M proliferation could be induced. These results show that in serum- deprived conditions, the multipoietins must be combined with lineage specific CSFs for full progenitor expression. 相似文献
996.
Interleukin-3 down-regulates its own receptor 总被引:4,自引:0,他引:4
To gain insight into the mechanisms involved in regulating murine interleukin-3 (mIL-3) receptor expression, we have examined the effects of mIL-3 and murine granulocyte-macrophage colony-stimulating factor (mGM-CSF) on mIL-3 receptor internalization and re-expression and studied the relationship between mIL-3 cell surface receptor density and growth factor sensitivity. As a source of cells for our studies, we used a B6SUtA clone, B6SUtA1, which grows equally well in mIL-3 or mGM- CSF when supplemented with 20% fetal calf serum (FCS) in RPMI 1640. Intracellular processing studies carried out in the presence and absence of methylamine suggested that mIL-3 is cleaved at two specific sites before its complete digestion within lysosomes. However, unlike its ligand, cycloheximide studies indicated that internalized mIL-3 receptors are recycled to the cell surface. When B6SUtA1 cells were continuously passaged in mIL-3, cell populations allowed to exhaust the mIL-3 in the medium (high density cells) expressed more than ten times (ie, approximately 100,000/cell) the mIL-3 receptor number of those growing exponentially at low cell concentrations (low density cells). Since the high density cells were no larger than the low density cells, the marked increase in mIL-3 receptor number per cell reflects a true up-regulation of receptor expression. A kinetic analysis of this up- regulation revealed that it begins within one hour of mIL-3 exhaustion. Moreover, proliferation assays with these two cell populations, using 3H-thymidine incorporation, suggested that the high density cells were 30-fold more responsive to mIL-3. However, when B6SUtA1 cells were passaged in mGM-CSF, there was no difference in mIL-3 receptor number between high density and low density cells (ie, approximately 100,000/cell). Identical studies carried out with another mIL-3 dependent cell line, 32D C3, demonstrated that this phenomenon was not unique to B6SUtA1 cells. 相似文献
997.
Objective: To investigate the influence of balance, fear of falling and pain on the type of gait aids used by low care residential older persons. Method: A cross‐sectional design was used. Valid and reliable measures of balance (Berg Balance Test), fear of falling (Falls Efficacy Scale) and pain (Geriatric Pain Measure) were collected. The influence of these clinical factors on the type of gait aid subjects used (no aid, stick or frame, or both) was analysed using one‐way anova for multiple independent groups. Results: Balance and fear of falling were significantly related to the type of gait aid subjects used (P < 0.05), whereas pain had no significant influence (P > 0.05). Conclusions: Balance and fear of falling are significantly associated with the type of gait aid used in this low care population and thus might be important clinical factors to consider when prescribing gait aids. The Berg Balance Test and the Falls Efficacy Scale appear to be useful quantitative tools that might assist this. 相似文献
998.
Frequent deletion of p16INK4a/MTS1 and p15INK4b/MTS2 in pediatric acute lymphoblastic leukemia 总被引:3,自引:2,他引:3
Okuda T; Shurtleff SA; Valentine MB; Raimondi SC; Head DR; Behm F; Curcio- Brint AM; Liu Q; Pui CH; Sherr CJ 《Blood》1995,85(9):2321-2330
The tandemly linked p16INK4aMTS1 and p15INK4b/MTS2 genes on chromosome 9, band p21 encode proteins that function as specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6. This locus undergoes frequent bi-allelic deletion in human cancer cell lines, suggesting that the encoded proteins may function as tumor suppressors. However, more recent analysis of primary tumor samples has shown a much lower frequency of abnormalities affecting this region, raising doubt over the importance of these proteins in human malignancies. Hemizygous deletions and rearrangements of chromosome 9, band p21, are among the most frequent cytogenetic abnormalities detected in pediatric acute lymphoblastic leukemia (ALL), occurring in approximately 10% of cases. To determine if the p16INK4a/p15INK4b locus might be the target of these chromosomal lesions, we analyzed both genes in primary clinical samples from 43 pediatric ALL patients using interphase fluorescence in situ hybridization, Southern blot analysis, and the polymerase chain reaction. Deletions of p16INK4a/p15INK4b were identified in 18 of 20 cases with cytogenetically observed abnormalities of 9p and 5 of 23 with apparently normal chromosomes 9p, with the majority containing bi- allelic deletions (16 homozygous/7 hemizygous). Although most homozygous deletions involved both genes, Southern blot analysis showed an interstitial deletion in a single case that was confined to p16INK4a, suggesting that p15INK4b was not the critical target gene in this case. Sequence analysis of both p16INK4a and p15INK4b in all seven cases with hemizygous deletions failed to show mutations within the coding regions of the retained alleles. In this select group of patients, deletion of p16INK4a/p15INK4b was associated with T-cell phenotype, nonhyperdiploid karyotype (< 50 chromosomes), and poor event- free survival. These findings indicate that deletion of the p16INK4a/p15INK4b locus is one of the most common genetic abnormalities so far detected in pediatric ALL, and that loss of one or more of these cell cycle kinase inhibitors is important in leukemogenesis. 相似文献
999.
Interleukin-4 induces programmed cell death (apoptosis) in cases of high-risk acute lymphoblastic leukemia 总被引:3,自引:1,他引:3
Manabe A; Coustan-Smith E; Kumagai M; Behm FG; Raimondi SC; Pui CH; Campana D 《Blood》1994,83(7):1731-1737
We investigated the effects of interleukin-4 (IL-4) on the survival of leukemic and normal B-cell progenitors cultured on bone marrow stroma. IL-4 (at 100 U/mL) was cytotoxic in 16 of 21 cases of B-lineage acute lymphoblastic leukemia, causing reductions in CD19+ cell numbers that ranged from 50% to greater than 99% (median 83.5%) of those in parallel cultures not exposed to the cytokine. All nine cases with the t(9;22)(q34;q11) or the t(4;11)(q21;q23), chromosomal features that are often associated with multidrug resistance and a fatal outcome, were susceptible to IL-4 toxicity. IL-4 cytotoxicity resulted from induction of programmed cell death (apoptosis); there was no evidence of cell killing mediated by T, natural killer, or stromal cells. IL-4 cytotoxicity extended to a proportion of normal B-cell progenitors. After 7 days of culture with IL-4 at 100 U/mL, fewer CD19+, CD34+ normal lymphoblasts (the most immature subset) survived: in five experiments the mean (+/- SEM) reduction in cell recoveries caused by IL-4 was 60.0% +/- 6.0%. By contrast, reductions in recovery of more differentiated bone marrow B cells (CD19+, CD34-, surface Ig+) were low (6.6% +/- 2.2%; P < .001 by t-test). Our findings indicate that IL-4 is cytotoxic for human B-cell precursors and support clinical testing of IL-4 in cases of high-risk lymphoblastic leukemia resistant to conventional therapy. 相似文献
1000.
Prolactin (PRL) is an important immunoregulatory hormone secreted by the
anterior pituitary gland. Hyperprolactinaemia has been implicated in the
pathogenesis of systemic lupus erythematosus (SLE). However, clinical
studies regarding the PRL level and lupus disease activity have yielded
contradictory results. The aim of our present study was, therefore, to
re-evaluate the association of PRL level and disease activity in SLE by
analysing a larger patient cohort and following them up serially.
Seventy-two consecutive SLE patients were recruited and the serum PRL level
was measured at each visit. Our results showed that hyperprolactinaemia
(> 500 mIU/l) occurred in 35% (25/72) of the patients. A total of 72%
(18/25) of the hyperprolactinaemic patients had mild elevation (arbitrarily
defined as 500-800 mIU/l) of the level only. No correlation could be found
between the PRL level and various clinical and serological parameters of
lupus disease activity. On serial follow-up of 44 patients, again no
correlation between PRL and disease activity could be demonstrated. We
conclude that hyperprolactinaemia occurs in some patients with SLE, but the
serum level of PRL does not correlate with clinical or serological disease
activity and is not a reliable marker for disease monitoring. The mechanism
and pathoaetiological and clinical significance of hyperprolactinaemia in a
small subset of SLE patients remain unclear and a longer follow-up is
necessary.
相似文献