Direct Anterior Approach and Perioperative Fracture With a Single-Taper Wedge Femoral Component.

BACKGROUND: Despite growing interest in direct anterior approach total hip arthroplasty, perioperative femoral fracture and early aseptic loosening are increasingly recognized complications. Previous research has documented the role of surgeon experience in association with these femoral complications. The purpose of this study was to explore the relationship between femoral component design and early periprosthetic femoral complications. METHODS: This was an extension of previous work with an updated patient cohort of 5090 consecutive direct anterior primary total hip arthroplasties at a single institution with a single-taper, wedge femoral stem comprising 4 variants involving length and geometry: group 1, full-length, standard profile; group 2, full-length, reduced distal profile; group 3, short-length, standard profile; and group 4, short-length, reduced distal profile. Records were reviewed retrospectively for the incidence of early postoperative periprosthetic fracture or aseptic loosening and analyzed with regard to patient demographics and femoral stem type. RESULTS: There were 42 (0.83%) periprosthetic femur complications observed in the early postoperative period. Increased age (P < .001) and female gender (P = .023) were significantly associated with incidence of femoral complications in univariate analysis, while age maintained this significant relationship in multivariate analysis (P < .001). There was a trend toward increased complication rate in patients receiving a short stem with full profile taper (1.27%, P = .0539). CONCLUSION: Despite an overall low rate of femoral complications after direct anterior total hip arthroplasty, the risk is increased in elderly patients and females. Furthermore, femoral stem design may portend an elevated risk of these complications.

Reduced Thigh Pain with Short Femoral Stem Design Following Direct Anterior Primary Total Hip Arthroplasty.

BACKGROUND: Thigh pain is a variably reported symptom in the postoperative period following primary total hip arthroplasty (THA) with a well-fixed cementless femoral implant. While research has identified stem size, stem alignment, and differences in modulus of elasticity between implant and host bone as potential sources of thigh pain, only one study has specifically examined the impact of variation in implant design within a single femoral stem design. The purpose of this work was to determine whether there were differences in the pain experienced by patients treated with two design variants of a femoral stem during direct anterior THA. MATERIALS AND METHODS: Patients undergoing primary direct anterior THA at a single center between 2011-2015 were included in the study. Those patients suffering extensive comorbidities and postoperative complications were excluded from analysis. Study subjects completed a pain drawing and scale questionnaire for the operative hip at least one year following surgery. A cementless, single-taper wedge, titanium femoral component design available in short- and standard-length variations was used in all cases. Pain outcomes were compared between these two femoral stem options. RESULTS: A total of 1347 patients (1536 THA) met inclusion criteria for the study and surveys were returned for 820 of these THAs. Demographic data and UCLA activity scores were similar between cohorts of patients receiving the short- and standard-length components. The most common locations of pain reported were in the lower back and trochanteric region, 28% and 24% respectively. Patients in the short-length cohort reported a significantly lower incidence of pain in the anterior thigh as compared to the standard-length cohort, 12% versus 19% respectively [p=0.007]. There was no difference in the number of patients experiencing moderate to severe intensity of anterior thigh pain between these two groups, 3% versus 5% respectively [p=0.36]. No other statistically significant differences were found in the incidence of pain in the lower back, buttock, groin, trochanter, lateral thigh, or posterior thigh regions between the two cohorts. CONCLUSION: While the lower back and trochanteric region may be the most frequent areas of pain experienced in patients at one-year or more postoperative from direct anterior THA, a significantly higher incidence of anterior thigh pain is found in those patients treated with a standard-length stem design as compared to the short design. This finding may be due to contact between the tip of the distal stem with the femoral diaphysis as has been theorized in previous research, which is circumvented with the short design variant.

Lateral Unicompartmental Knee Arthroplasty Utilizing a Modified Surgical Technique and Specifically Adapted Fixed-Bearing Implant.

BACKGROUND: Treatment of isolated lateral compartment arthritic disease with partial knee arthroplasty remains underutilized in comparison to medial unicompartmental arthroplasty. This study examines the survival and outcome of lateral unicompartmental arthroplasty utilizing the first implant specifically developed for the lateral compartment. MATERIALS AND METHODS: A retrospective review was performed to detect lateral unicompartmental arthroplasty procedures performed in our practice between January 2013 and May 2016. Patients indicated for surgery met specific preoperative clinical and radiographic criteria confirming lateral compartment arthritic disease with a correctable deformity, intact full-thickness medial cartilage, competent anterior cruciate ligament, and minimal disease in the patellofemoral compartment. A single implant design was used in all cases which consisted of a fixed-bearing tibial component specifically adapted to lateral compartment anatomy. Unicompartmental arthroplasty surgical technique was adjusted to attempt to recreate lateral compartment kinematics. RESULTS: Fifty-two consecutive patients (56 knees) with lateral unicompartmental arthroplasty procedures meeting minimum two-year follow up were included in the study. Thirty-nine patients were female, and 93% of cases were performed for treatment of osteoarthritis. At a mean follow up of nearly three years, Knee Society clinical and functional scores improved postoperatively by a mean difference of 41 and 21, respectively. There were two reoperations, one medial unicompartmental arthroplasty for osteoarthritis progression and a superficial debridement for a non-healing wound. Thus, failure of lateral unicondylar knee arthroplasty (UKA) was less than 2% in this study. There were no other component revisions, radiographic evidence of loosening, or clinical failures. CONCLUSIONS: At early follow up, lateral unicompartmental arthroplasty using a modified surgical technique and an implant specifically designed for the lateral compartment is a reliable treatment for isolated lateral femorotibial arthritis when meeting defined indications.

"Thicker" Polyethylene Bearings Are Not Associated With Higher Failure Rates in Primary Total Knee Arthroplasty.

BACKGROUND: Despite improvements in polyethylene bearing surface properties, only 1 previous study has examined the results of larger thickness bearings. The purpose of this study was to determine whether polyethylene thickness influenced patient outcomes and implant survival following modular total knee arthroplasty. METHODS: A retrospective review was performed of patients undergoing primary total knee arthroplasty from 2003 to 2014 in a single practice database. Patients were separated into "thin" and "thick" polyethylene groups based on manufacturer polyethylene bearing sizes of 14 mm or less compared to those greater than 14 mm, respectively. Patient clinical outcomes, need for revision surgery, and overall implant survival rates were evaluated. RESULTS: A total of 6698 primary knee arthroplasties were included, and a thin bearing was used in 96.5% of these cases. Preoperatively, patients with a thick bearing had significantly lower Knee Society clinical scores (P < .01), a trend toward lower functional scores (P = .06), and more significant coronal plane deformity. Postoperatively, patients with thick bearings exhibited better Knee Society clinical and pain scores as well as similar functional scores and University of California at Los Angeles activity scores. The overall reoperation rate and 10-year survivorship free of revision were similar between thick and thin bearings (1.7% vs 2.3%; 98.2% vs 96.1%). Patients with thin bearings were twice as likely to require a manipulation under anesthesia postoperatively (P = .02), while there were no failures in the thick bearing group due to aseptic loosening or instability. CONCLUSION: Patients with thick polyethylene bearings performed similarly or better in multiple clinical outcomes and survivorship compared to those with thin bearings.

Medial Mobile-Bearing Unicompartmental Knee Arthroplasty in Young Patients Aged Less Than or Equal to 50 Years.

BACKGROUND: Contemporary research has shown medial mobile-bearing unicompartmental knee arthroplasty to be an effective treatment in patients younger than 60 years; however, only one other study has specifically investigated unicompartmental arthroplasty outcomes in patients 50 years or younger. The purpose of this study was to determine the clinical outcomes and survivorship of medial mobile-bearing unicompartmental arthroplasty in this younger patient population. METHODS: A retrospective review of patients undergoing primary unicompartmental knee arthroplasty using the Oxford partial knee from 2003 to 2014 in a single practice database was performed. Patients were included in the study if they were 50 years of age or younger with a primary diagnosis of anteromedial osteoarthritis and minimum clinical follow-up of 2 years. Patient clinical outcomes, function, and need for revision surgery were assessed. RESULTS: The study included 340 knees. Average patient age was 46.5 years, and the mean follow-up was 6.1 years. Patients demonstrated significant improvements (P < .05) in range of motion (114.5 v 116.9), University of California Los Angeles activity score (4.4 vs 5.6), Knee Society clinical (37.3 vs 86.5) and functional scores (58.8 v 79.8). Overall, 20 patients required reoperation, and the predicted survival rate was 96% at 6 years and 86% at 10 years. Aseptic loosening occurred in 7 patients at an average of 5.6 years postoperatively, while 4 patients required conversion to total knee arthroplasty because of arthritic progression at a mean time of 6.6 years. There were no revision procedures required due to polyethylene liner wear or breakage. CONCLUSION: Medial mobile-bearing unicompartmental arthroplasty should be considered as a treatment option in patients younger than 50 years of age suffering from anteromedial osteoarthritis of the knee.

The rapid recovery study: Cyclobenzaprine's effect on recovery following joint arthroplasty.

Introduction: Skeletal muscle relaxants have previously not been examined in multimodal anesthesia regimens following joint arthroplasty. We sought to evaluate cyclobenzaprine's effect on postoperative opioid consumption as well as surgical recovery following joint arthroplasty. Materials and methods: In this retrospective cohort study, 471 patients undergoing 554 joint arthroplasty procedures were evaluated. Patients were divided into cohorts who did and did not receive cyclobenzaprine postoperatively, and postoperative opioid consumption and functional recovery measures were recorded in each cohort. Results: In the unadjusted model, the cyclobenzaprine cohort experienced a 1.11 increase in pain scores on postoperative day zero (95% CI (0.60, 1.62), p < 0.0001). After adjusting for age, sex, BMI, CCI, perioperative MME, laterality, procedure, anesthesia, pre-op opioid use, pre-operative other controlled substance uses and pre-op benzodiazepine use, the cyclobenzaprine cohort's pain scores were 1.08 units higher at rest (95% CI (0.59, 1.56), p < 0.0001) and 1.25 units higher with activity on postoperative-day-zero (95% CI (0.78, 1.72), p < 0.0001). Both cohorts experienced statistically insignificantly different changes in mobility scores between postoperative day zero and postoperative day one, range of motion at 6 and 12 weeks, and readmission in <90 days. Postoperative morphine milliequivalents were insignificantly different between cohorts after controlling for pain in all models (base model mean ratio: 1.06, 95% CI (0.87,1.29), p = 0.5599) (Full model mean ratio: 1.09, 95% CI (0.91,1.30), p = 0.3608). Conclusions: Cyclobenzaprine shows utility in a multimodal anesthetic approach after joint arthroplasty in patients with higher baseline pain.

Umbilical cord blood-derived very small embryonic like stem cells (VSELs) as a source of pluripotent stem cells for regenerative medicine.

Umbilical cord blood-derived very small embryonic-like stem cells (UCB-VSELs) are the most primitive stem cells circulating in fetal peripheral blood. These very rare cells slightly smaller than red blood cells i) become mobilized during delivery, ii) are enriched in fraction of CD133+ Lin-CD45- cells iii) express markers of pluripotent stem cells (e.g., Oct4, Nanog, and SSEA-4) and iv) display a distinct morphology characterized by a high nuclear/ cytoplasmic ratio and undifferentiated chromatin. We envision that VSELs are released into neonatal peripheral blood as a migrating population of stem cells involved in regeneration of tissues that become damaged in the process of delivery. They may also be responsible for the occurrence of fetal-maternal chimerism. Our most recent data suggest that UCB-VSELs exhibit some characteristics of long-term repopulating hematopoietic stem cells (LT-HSCs). We propose that UCB-VSELs may eventually be employed as a source of pluripotent stem cells in regenerative medicine.

microRNA 184 regulates expression of NFAT1 in umbilical cord blood CD4+ T cells.

The reduced expression of nuclear factor of activated T cells-1 (NFAT1) protein in umbilical cord blood (UCB)-derived CD4+ T cells and the corresponding reduction in inflammatory cytokine secretion after stimulation in part underlies their phenotypic differences from adult blood (AB) CD4+ T cells. This muted response may contribute to the lower incidence and severity of high-grade acute graft-versus-host disease (aGVHD) exhibited by UCB grafts. Here we provide evidence that a specific microRNA, miR-184, inhibits NFAT1 protein expression elicited by UCB CD4+ T cells. Endogenous expression of miR-184 in UCB is 58.4-fold higher compared with AB CD4+ T cells, and miR-184 blocks production of NFAT1 protein through its complementary target sequence on the NFATc2 mRNA without transcript degradation. Furthermore, its negative effects on NFAT1 protein and downstream interleukin-2 (IL-2) transcription are reversed through antisense blocking in UCB and can be replicated via exogenous transfection of precursor miR-184 into AB CD4+ T cells. Our findings reveal a previously uncharacterized role for miR-184 in UCB CD4+ T cells and a novel function for microRNA in the early adaptive immune response.

Model-based tracking of the hip: implications for novel analyses of hip pathology.

This study investigated the efficacy of a combined high-speed, biplane radiography and model-based tracking technique to study hip joint kinematics and arthrokinematics. Comparing model-based tracking to the gold standard of radiostereometric analysis using implanted metal beads, joint translation was measured with a bias of 0.2 mm and a precision of 0.3 mm, whereas joint rotation was measured with a bias of 0.2° and a precision of 0.8°. A novel measure of hip arthrokinematics characterizing the region of closest contact in the anterosuperior acetabulum was measured with a bias of 0.9% and a precision of 2.5%. Model-based tracking of the hip thus provides the opportunity to noninvasively study hip pathologic conditions such as osteoarthritis and femoroacetabular impingement with great accuracy.

Medial Osteoarthritis in an ACL-Deficient Knee: A Critical Analysis Review.

¼: In anterior cruciate ligament (ACL)-deficient knees, treatment of medial compartment osteoarthritis (OA) that is refractory to nonoperative modalities is a controversial subject. ¼: Currently available treatment options include unicompartmental knee arthroplasty (UKA) with or without ACL reconstruction (ACLR), high tibial osteotomy (HTO) with or without ACLR, and total knee arthroplasty (TKA). ¼: Each treatment option has its own risks and benefits, and the evidence that is reviewed in this article suggests that patient characteristics guide treatment selection. ¼: Future high-quality prospective studies that directly compare all 3 of the modalities are necessary to determine the best treatment option for different patient populations.

Umbilical cord blood-selected CD133(+) cells exhibit vasculogenic functionality in vitro and in vivo.

BACKGROUND AIMS: Current clinical trials utilize non-selected bone marrow (BM) mononuclear cells (MNC) to augment vasculo genesis within ischemic vascular beds. Recent reports have identified a diminished number and function of hemat-opoietic stem cells (HSC) from aged and diseased patients. Umbilical cord blood (UCB) provides a potential robust allo-geneic source of HSC for therapeutic vasculogenesis. METHODS: MNC and magnetically isolated CD133(+) cells were assessed for viability (trypan blue) and surface phenotype (flow cytometry). To test in vivo functionality of the cells, NOD/SCID mice underwent ligation of the right femoral artery followed immediately by cell injection. Blood flow recovery, necrosis, BM engraftment of human cells and histologic capillary density were determined. Cells were tested for potential mechanisms mediating the in vivo effects, including migration, cytokine secretion and angiogenic augmentation (Matrigel assays). RESULTS: Surface expression analysis showed CD31 (PECAM) expression was greatly increased in UCB CD133(+) cells compared with BM MNC. At 28 days, perfusion ratios were highest in animals receiving UCB CD133(+) cells, while animals receiving BM CD133(+) cells and BM MNC demonstrated perfusion ratios statistically higher than in animals treated with cytokine media alone. Animals receiving CD133(+) cells showed a statistically higher capillary density, reduced severe digit necrosis and increased engraftment in the BM than animals treated with unselected BM MNC. In vitro studies showed equivalent migration to stromal-derived factor-1 (SDF-1), increased production of tumor necrosis factor alpha (TNF-alpha) and increased branch points with the co-incubation of CD133(+) cells with human umbilical vein endothelial cells (HUVEC) in the Matrigel angiogenesis assay. CONCLUSIONS: Taken together, UCB CD133(+) cells exhibit robust vasculogenic functionality compared with BM MNC in response to ischemia.

Outcome reporting patterns in total knee arthroplasty: A systematic review.

BACKGROUND: Total knee arthroplasty (TKA) is one of the most effective ways to treat end-stage painful conditions of the knee. However, non-standardized reporting patterns can make quantitative analysis of patient outcomes difficult. METHODS: A systematic review of the literature was performed using keywords "total knee arthroplasty" and "total knee replacement." Randomized controlled trials (RCTs) meeting the inclusion criteria were sorted and reviewed. Type of study, outcome measures used to report their results, and the actual results were recorded. Quantitative analysis was performed. RESULTS: A total of 233 RCTs were included. There was significant variability in the reporting of short term and long term outcomes in total knee arthroplasty. The most common treatment domains in order of decreasing frequency were objective knee function, subjective knee function, perioperative complications, and pain. Range of motion was the most common outcome metric reported in all the RCTs and also was the most common metric used to assess objective knee function. The most common patient reported outcome measure used to assess postoperative function was the Knee Society Score followed by Knee Injury and Osteoarthritis Outcome Score. The Visual Analog Scale was the most common measurement tool used to assess postoperative pain. Most studies assessed patient outcomes in three treatment domains. None reported outcomes in all seven domains. CONCLUSION: There is significant variability in outcome reporting patterns in TKA literature. Most studies do not track outcomes comprehensively, with a significant minority of the RCTs tracking outcomes in only one treatment domain.

Medial Unicompartmental Knee Arthroplasty for the Treatment of Focal Femoral Osteonecrosis.

BACKGROUND: Previous research has indicated that unicompartmental arthroplasty may be an effective treatment for focal osteonecrosis in the knee; however, these reports have been composed of small patient cohorts and without characterization of the osteonecrotic lesions. Therefore, the purpose of this study was to investigate the effectiveness of unicompartmental arthroplasty for the treatment of focal osteonecrosis within the medial femoral condyle including an assessment of lesion size. METHODS: A consecutive series of >5,000 unicompartmental knee arthroplasties performed at a single institution was retrospectively reviewed to identify cases of medial femoral condyle osteonecrosis with a minimum 2-year follow-up. Lesion size was classified according to the ratio of lesion width to condylar width, as well as lesion depth relative to condylar depth. Patient-reported outcome measures and need for a revision procedure were studied. RESULTS: Sixty-four patients (32 males, 32 females; 65 knees) with a mean age of 64 years were included. The mean patient follow-up was 5.3 years (range, 2 to 12 years). The mean ratio of lesion width to condylar width was 64%, the mean lesion depth was 1.11 cm, and 82% of cases demonstrated subchondral collapse. At the time of the latest follow-up, patients demonstrated substantial improvements in the pain, function, and clinical components of the Knee Society Score, by 36, 25, and 51, respectively. Four patients (6%) required a revision, of which only 1 was for aseptic loosening of the femoral component. CONCLUSIONS: Unicompartmental arthroplasty is an effective treatment for advanced-stage focal osteonecrosis of the medial femoral condyle. Loss of component fixation to the femoral condyle did not appear to be a substantial concern because there was only 1 femoral failure as a result of aseptic loosening, despite lesions affecting a significant portion of the femoral condyle. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Furan Decorated Nucleoside Analogues as Fluorescent Probes: synthesis, photophysical evaluation and site-specific incorporation.

The synthesis and photophysical evaluation of modified nucleoside analogues in which a five-membered heterocycle (furan, thiophene, oxazole and thiazole) is attached to the 5 position of 2'-deoxyuridine are reported. The furan containing derivative is identified as the most promising responsive nucleoside of this family due to its emission quantum efficiency and degree of sensitivity to its microenvironment. The furan moiety was then attached to the 5 position of 2'-deoxycytidine as well as the 8 position of adenosine and guanosine. Photophysical evaluation of these four furan containing nucleoside analogues reveal distinct differences in the absorption, emission and quantum efficiency depending upon the class of nucleoside (pyrimidine or purine). Comparing the photophysical properties of all furan containing nucleosides, identifies the furan thymidine analogue, 5-(fur-2-yl)-2'-deoxyuridine, as the best candidate for use as a responsive fluorescent probe in nucleic acids. 5-(fur-2-yl)-2'-deoxyuridine was then converted to the corresponding phosphoramidite and site specifically incorporated into DNA oligonucleotides with greater than 88% coupling efficiency. Such furan-modified oligonucleotides form stable duplexes upon hybridization to their complementary DNA strands and display favorable fluorescent features.

Factor VIIIa regulates substrate delivery to the intrinsic factor X-activating complex.

Activation of coagulation factor X (fX) by activated factors IX (fIXa) and VIII (fVIIIa) requires the assembly of the enzyme-cofactor-substrate fIXa-fVIIIa-fX complex on negatively charged phospholipid membranes. Using flow cytometry, we explored formation of the intermediate membrane-bound binary complexes of fIXa, fVIIIa, and fX. Studies of the coordinate binding of coagulation factors to 0.8-microm phospholipid vesicles (25/75 phosphatidylserine/phosphatidylcholine) showed that fVIII (fVIIIa), fIXa, and fX bind to 32 700 +/- 5000 (33 200 +/- 14 100), 20 000 +/- 4500, and 30 500 +/- 1300 binding sites per vesicle with apparent K(d) values of 76 +/- 23 (71 +/- 5), 1510 +/- 430, and 223 +/- 79 nm, respectively. FVIII at 10 nm induced the appearance of additional high-affinity sites for fIXa (1810 +/- 370, 20 +/- 5 nm) and fX (12 630 +/- 690, 14 +/- 4 nm), whereas fX at 100 nm induced high-affinity sites for fIXa (541 +/- 67, 23 +/- 5 nm). The effects of fVIII and fVIIIa on the binding of fIXa or fX were similar. The apparent Michaelis constant of the fX activation by fIXa was a linear function of the fVIIIa concentration with a slope of 1.00 +/- 0.12 and an intrinsic K(m) value of 8.0 +/- 1.5 nm, in agreement with the hypothesis that the reaction rate is limited by the fVIIIa-fX complex formation. In addition, direct correlation was observed between the fX activation rate and formation of the fVIIIa-fX complex. Titration of fX, fVIIIa, phospholipid concentration and phosphatidylserine content suggested that at high fVIIIa concentration the reaction rate is regulated by the concentration of free fX rather than of membrane-bound fX. The obtained results reveal formation of high-affinity fVIIIa-fX complexes on phospholipid membranes and suggest their role in regulating fX activation by anchoring and delivering fX to the enzymatic complex.

Evaluation of the reactivity of apoptosis markers before and after cryopreservation in cord blood CD34(+) cells.

Umbilical cord blood (CB) CD34(+) cells, on the basis of flow cytometry analysis, are comprised of multiple populations. In in vitro assays, only CD34(regular) FSC(high) cells are functional and low percentages of nonfunctional CD34(regular) FSC(low) cells were determined to be present in liquid-stored CB. Liquid-stored CD34(regular) FSC(high) cells prior to cryopreservation were judged to be functional by the formation of erythroid and myeloid colonies and transmigration assays. We have further evaluated the occurrence of apoptosis in CB CD34(+) cells using various apoptotic markers to understand better the influence of storage conditions that could be utilized with transplantation of CB. Of the CD34(regular) FSC(low) cells shown in the present study, 20-45% were labeled with the apoptotic reagents annexin-V, fluorescent caspase peptide substrates, and the anti-mitochondrial antibody APO2.7, but these cells were minimally stained with 7-aminoactinomycin-D (7-AAD). These apoptotic reagents identify different cellular targets, indicating the initiation of the apoptotic cascade prior to cryopreservation/thawing. Following cryopreservation and thawing, the apoptotic markers SYTO-16, tetramethyl rhodamine ethyl ester (TMRE), and 7-AAD showed the presence of apoptotic cells. After cryopreservation/thawing, enumeration of CB CD34(+) cells was reduced 10-65% when excluding cells positive for apoptotic markers. We attempted to limit the progression of apoptosis observed after cryopreservation/thawing by the addition of anti-apoptotic reagents z-VAD-fmk (100 microM) and Q-VD-OPH (100 microM) (peptide inhibitors of caspases) without or with the inclusion of survival reagents for CD34(+) cells-stromal-derived factor-1 (SDF-1), stem cell factor (SCF), thrombopoietin, and diprotin A, an inhibitor of CD26 prior to cryopreservation. The expression of apoptosis markers was minimally affected even when using combinations of caspase inhibitors/ CD34(+) cell survival cytokines in an attempt to block apoptosis caused by cryopreservation/thawing. Decreases in apoptosis marker reactivity following cryopreservation were not observed except for a reduced expression of APO2.7 reactivity with z-VAD-fmk and Q-VD-OPH caspase inhibitors. The ability of the inhibitors of apoptosis of CD34(+) cells to generate CFU-GM, CFU-MK, or BFUE colonies was also unaffected except with z-VAD-fmk (100 microM) and Q-VD-OPH (100 microM). The occurrence of apoptosis, as measured by flow cytometry with selected apoptotic markers, suggests a reduction in the number of viable CD34(+) cells.

Posterior Shoulder Instability in Overhead Athletes.

Posterior shoulder instability in overhead athletes presents a unique and difficult challenge. Often, this group has an inherent capsular laxity and/or humeral retroversion to accommodate the range of motion necessary to throw. This adaptation makes the diagnosis of posterior capsulolabral pathology challenging, as the examiner must differentiate between adaptive capsular laxity and pathologic instability. Further complicating matters, the intraoperative surgeon must find the delicate balance of achieving stability while still allowing the necessary range of motion.

Weak platelet agonists and U46619 induce apoptosis-like events in platelets, in the absence of phosphatidylserine exposure.

Platelets express apoptotic markers during storage, while aging and after stimulation with strong agonists thrombin and collagen. It is unknown if the weak agonists ADP and epinephrine or U46619, a thromboxane analog, induce the expression of apoptotic markers in platelets. To answer this question, we measured phosphatidylserine exposure, gelsolin cleavage and decrease in membrane mitochondrial potential after stimulation with these agonists. No phosphatidylserine exposure was evident, however, gelsolin cleavage and a platelet population with a decreased membrane mitochondrial potential appeared, suggesting that in platelets selective agonists can induce apoptosis in the absence of phosphatidylserine exposure. Interestingly, costimulation by thrombin plus collagen together with each of the other agonists increased the phosphatidylserine exposure induced by strong agonists. These findings may be of importance in platelet activation and apoptosis under pathophysiological conditions where multiple effectors are involved.