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11.
Chukwuka C Okafor Hana Haleem-Smith Patrice Laqueriere Paul A Manner Rocky S Tuan 《Journal of orthopaedic research》2006,24(3):461-473
Continual loading and articulation cycles undergone by metallic (e.g., titanium) alloy arthroplasty prostheses lead to liberation of a large number of metallic debris particulates, which have long been implicated as a primary cause of periprosthetic osteolysis and postarthroplasty aseptic implant loosening. Long-term stability of total joint replacement prostheses relies on proper integration between implant biomaterial and osseous tissue, and factors that interfere with this integration are likely to cause osteolysis. Because multipotent mesenchymal stem cells (MSCs) located adjacent to the implant have an osteoprogenitor function and are critical contributors to osseous tissue integrity, when their functions or activities are compromised, osteolysis will most likely occur. To date, it is not certain or sufficiently confirmed whether MSCs endocytose titanium particles, and if so, whether particulate endocytosis has any effect on cellular responses to wear debris. This study seeks to clarify the phenomenon of titanium endocytosis by human MSCs (hMSCs), and investigates the influence of endocytosis on their activities. hMSCs incubated with commercially pure titanium particles exhibited internalized particles, as observed by scanning electron microscopy and confocal laser scanning microscopy, with time-dependent reduction in the number of extracellular particles. Particulate endocytosis was associated with reduced rates of cellular proliferation and cell-substrate adhesion, suppressed osteogenic differentiation, and increased rate of apoptosis. These cellular effects of exposure to titanium particles were reduced when endocytosis was inhibited by treatment with cytochalasin D, and no significant effect was seen when hMSCs were treated only with conditioned medium obtained from particulate-treated cells. These findings strongly suggest that the biological responses of hMSCs to wear debris are triggered primarily by the direct endocytosis of titanium particulates, and not mediated by secreted soluble factors. In this manner, therapeutical approaches that suppress particle endocytosis could reduce the bioreactivity of hMSCs to particulates, and enhance long-term orthopedic implant prognosis by minimizing wear-debris periprosthethic osteolysis. 相似文献
12.
Paul C. Willems Leon Elmans Patricia G. Anderson Wilco C. H. Jacobs Dick B. van der Schaaf Marinus de Kleuver 《European spine journal》2006,15(10):1487-1494
The results of lumbar fusion in chronic low back pain (LBP) patients vary considerably, and there is a need for proper patient selection. Lumbosacral orthoses have been widely used to predict outcome, however, with little scientific support. The aim of the present study was to determine the value of a pantaloon cast test in selecting chronic LBP patients for lumbar fusion or conservative management. First, a systematic review of the literature was carried out in which two independent reviewers identified studies in Medline, Cochrane and Current Contents databases. Three papers met the selection criteria. In the only study with a control group, a significantly better outcome after fusion compared to conservative treatment was found in patients who reported significant pain relief while in a cast (i.e. a positive cast test). The results of lumbar fusion, however, were not significantly different for patients with a positive and those with a negative cast test. In addition to the review, a clinical cohort study of 257 LBP patients, who had been allocated to either lumbar fusion or conservative management by a temporary external transpedicular fixation trial, was performed. Prior to allocation, all had undergone a pantaloon cast test. Patients with no history of prior spine surgery and with a positive pantaloon cast test had a better outcome after lumbar fusion than those treated conservatively (P = 0.002, χ
2 test). In patients with previous spine operations the outcomes were poor and the test was of no value. From the literature and the present patient cohort, it was concluded that only in chronic LBP patients without prior spine surgery, a pantaloon cast test with substantial pain relief suggests a favorable outcome of lumbar fusion compared to conservative management. The test has no value in patients who have had previous spine surgery. 相似文献
13.
Costas D Lallas Erik P Castle Richard T Schlinkert Paul E Andrews 《JSLS, Journal of the Society of Laparoendoscopic Surgeons》2006,10(2):135-140
BACKGROUND AND OBJECTIVES: In 1999, our institution began a kidney transplant program with collaboration between the departments of General Surgery/Transplantation and Urology. From the onset, donor nephrectomies were performed laparoscopically and are currently the domain of Urology, which had no prior laparoscopic experience before this undertaking. We reviewed our experience. METHODS: A database of our experience was kept prospectively from June 1999 to November 2004. Records of both donors and recipients were reviewed. Special attention was directed toward our changes in technique and their relationship to outcomes, with emphasis on graft extraction and overall complication rates. RESULTS: We reviewed the records of 205 consecutive procedures. We report excellent donor outcomes, including mean operative time (112 minutes), estimated blood loss (120 mL), and length of stay (2.3 days). Complication (14.1%) and open conversion (1.5%) rates were low. For the recipients, early (98.0%) and 1-year (94.7%) graft survival, and ureteral ischemia (2.4%) rates were also appropriate with contemporary experience. CONCLUSIONS: We report our results on laparoscopic donor nephrectomy in a de novo renal transplant program. Because of this experience, we have ventured into other horizons of urologic laparoscopy and currently produce enough volume to support a laparoscopic fellowship. We feel that a productive donor nephrectomy program can enhance urologic laparoscopic programs and should be taken advantage of when available. 相似文献
14.
15.
Paul A Dabisch Emily A Davis Michael S Horsmon Robert J Mioduszewski 《Journal of ocular pharmacology and therapeutics》2006,22(5):323-332
The organophosphorous nerve agent sarin (GB) and the carbamate pyridostigmine bromide (PB) both inhibit acetylcholinesterase (AChE), leading to overstimulation of muscarinic receptors. Both GB and PB produce miosis through stimulation of ocular muscarinic receptors. This study investigated 2 hypotheses: (1) that the miotic response to PB would decrease following repeated injections; and (2) that repeated administration of PB would result in tolerance to the miotic effect of GB vapor. Rats were injected intramuscularly with saline, 0.04 mg/kg, 0.5 mg/kg, or 1.4 mg/kg of PB twice daily for 8 consecutive days. After day 3, animals injected with 1.4 mg/kg PB developed miotic tolerance. Twenty-four (24) h following the final PB injection, the rats were exposed to GB vapor (4.0 mg/m(3)). A similar magnitude of miosis was observed in all groups after GB exposure. However, the rate of recovery of pupil size in animals pretreated with 0.5 and 1.4 mg/kg PB was significantly increased. Twenty (20) h following exposure to GB vapor, the pupils of animals pretreated with 1.4 mg/kg PB had recovered to 77% +/- 4% of their pre-exposure baseline, whereas the saline-injected controls had recovered to only 52% +/- 2% of their pre-exposure baseline. The increased rate of recovery does not appear to be a result of protection of pupillary muscarinic receptors by the higher doses of PB, as there was no longer PB present in the animal at the time of GB exposure. These results demonstrate the development of tolerance to the miotic effect of PB following repeated exposures, and also suggest that cross-tolerance between PB and GB occurs. However, because the magnitude of the response was not reduced, the PB pretreatment and its associated miotic cross-tolerance does not appear to diminish the effectiveness of miosis as a biomarker of acute exposure to nerve agent vapor. 相似文献
16.
Matthew S Lewis Paul Maruff Brendan S Silbert Lis A Evered David A Scott 《Archives of clinical neuropsychology》2006,21(5):421-427
The reliable change index (RCI) expresses change relative to its associated error, and is useful in the identification of post-operative cognitive dysfunction (POCD). This paper examines four common RCIs that each account for error in different ways. Three rules incorporate a constant correction for practice effects and are contrasted with the standard RCI that had no correction for practice. These rules are applied to 160 patients undergoing coronary artery bypass graft (CABG) surgery who completed neuropsychological assessments preoperatively and 1 week post-operatively using error and reliability data from a comparable healthy non-surgical control group. The rules all identify POCD in a similar proportion of patients, but the use of the within subject standard deviation, expressing the effects of random error, as an error estimate is a theoretically appropriate denominator when a constant error correction, removing the effects of systematic error, is deducted from the numerator in a RCI. 相似文献
17.
Henk R Franke F Froukje Snaaijer Paul W H Houben Marius J van der Mooren 《Gynecological endocrinology》2006,22(12):692-697
OBJECTIVE: To assess the effects of adding combined estradiol/norethisterone acetate therapy (CENT) to goserelin acetate treatment (GA) of dysfunctional uterine bleeding (DUB) in perimenopausal women. METHODS: In a randomized, placebo-controlled, double-blind trial followed by an open follow-up study, 31 perimenopausal women with DUB were recruited from gynecological outpatient departments of two Dutch hospitals and randomized for treatment with either GA/placebo or GA/CENT for 6 months followed by 18 months of GA/CENT for all. The main outcome measures were abdominal pain, number of bleeding days, double-layer endometrial thickness (DET), Greene climacteric score (GCS), visual analog scale for well-being, bone mineral density (BMD) and mammographic density (BI-RAD score). RESULTS: Abdominal pain, number of bleeding days and DET decreased in both groups, the between-group difference in decrease not being statistically significant. GCS initially showed significant improvement in the GA/CENT group. BMD decreased significantly in the GA/placebo group (-4.1%) compared with the GA/CENT group (-0.3%). Another 18 months of GA/CENT did not result in a lasting difference in BMD between groups. BI-RAD scores did not differ significantly between or within the two groups. CONCLUSIONS: Adding CENT to GA treatment for DUB in perimenopausal women initially prevented BMD loss and improved climacteric complaints, while having no negative impact on vaginal bleeding, abdominal pain or BI-RAD scores. However, prolonged treatment did not result in a lasting prevention of bone loss. 相似文献
18.
PURPOSE: Concern over stigma as a consequence of genetic testing has grown in response to the recent increase in genetic research and testing resulting from the Human Genome Project. However, whether a genetic or hereditary basis necessarily confers a stigma to a condition remains unexamined. METHODS: We performed a qualitative interview study with 86 individuals with one of four conditions: deafness or hearing loss, breast cancer, sickle cell disease, and cystic fibrosis. The first two groups were divided approximately between people who ascribed their conditions to a genetic or hereditary cause and those who did not. RESULTS: Respondents interpreted genetic or hereditary causes and nongenetic causes in a variety of ways. Subjects with breast cancer reported the most consistently negative interpretation of genetic cause. This response concerned future ill health, not an enduring sense of stigma. Deaf and hard of hearing subjects provided the most consistently positive comments about a genetic or hereditary basis to their condition, casting familial hearing loss as a vital component of group and individual identity. Respondents with sickle cell disease and cystic fibrosis offered similar and positive interpretations of the genetic cause of their condition insofar as it meant their conditions were not contagious. CONCLUSIONS: Although some subjects report feeling stigmatized as a result of their condition, this stigmatization is not uniformly associated with the condition's cause, genetic or otherwise. Instead, stigma emerges from a variety of sources in the context of the lived experience of a particular condition. 相似文献
19.
20.
Abraham Nudelman Yitschak Binnes Naomi Shmueli-Broide Yael Odessa J. Paul Hieble Anthony C. Sulpizio 《Archiv der Pharmazie》1996,329(3):125-132
Vinylogous (Groups III and V ) and acetylenologous (Group IV ) analogs of the classical β-adrenergic agents — stimulants and blockers — were prepared in order to evaluate the effect of degree of saturation, position of unsaturation and rigidity of the chain linking the aromatic ring and the amino containing functional group on biological activity. Derivatives from Group III , which represent 4-aryl-3-butenyl-2-ol-amine analogs of Group II , retained β1-adrenoceptor antagonist activity albeit substantially less potent (50–200-fold) than that possessed by their aryloxy counterparts. Consistent with the SAR for Group II compounds, substitution at position 2 of the aromatic ring yielded the most potent antagonists ( 5a, 5d, 5g ), with KB's ranging from 73–93 nM while 3,4-dichloro substitution ( 5e ) markedly reduced antagonist potency (KB = 2,400 nM). Agonist activity was also noted for 5b and 5d , suggesting that these compounds may be best classified as partial agonists. Representatives from Groups IV and V were inactive as antagonists at the β1-adrenoceptor confirming the importance of the spatial relationship between the hydroxyl and the amino nitrogen. 相似文献