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991.
Dramatic changes in muscle contractile and structural properties after 2 botulinum toxin injections 下载免费PDF全文
Viviane B. Minamoto PT PhD Kentaro P. Suzuki MD Shannon N. Bremner BS Richard L. Lieber PhD Samuel R. Ward PT PhD 《Muscle & nerve》2015,52(4):649-657
Introduction: Botulinum toxin is frequently administered serially to maintain therapeutic muscle paralysis, but the effect of repeated doses on muscle function are largely unknown. This study characterized the muscle response to 2 onabotulinum toxin (BoNT) injections separated by 3 months. Methods: Animal subjects received a single toxin injection (n = 8), 2 BoNT injections separated by 3 months (n = 14), or 1 BoNT and 1 saline injection separated by 3 months (n = 8). Results: The functional effect of 2 serial injections was exponentially greater than the effect of a single injection. While both groups treated with a single BoNT injection had decreased torque in the injected leg by approximately 50% relative to contralateral legs, the double BoNT injected group had decreased torque by over 95% relative to the preinjection level. Both single and double BoNT injections produced clear signs of fiber‐type grouping. Conclusions: These experiments demonstrate a disproportionately greater effect of repeated BoNT injections. Muscle Nerve 52: 649–657, 2015 相似文献
992.
The clinical application of gene transfer is hindered by the availability of the multipotential stem cells and the difficulty in obtaining efficient retroviral transduction. To assess potential means by which gene transfer into human hemopoietic stem cells might be enhanced, the retroviral transduction efficiency of human bone marrow cells (BM) or peripheral blood progenitor cells (PBPC) was compared at multiple time points after in vivo administration of granulocyte colony- stimulating factor (G-CSF). This was further compared with the transduction efficiency of cells mobilized with G-CSF plus stem cell factor (SCF) in a cohort of patients randomized to receive either one or two growth factors and with normal BM function. Using the LNL6 retrovirus, retroviral transduction efficiencies of up to 19% were observed for both PBPC and BM (n = 26 patients). There was at least a 100-fold increase in PBPC with G-CSF alone and a further 30-fold increase in the total number of progenitor cells available for retroviral transduction using the combination of SCF plus G-CSF. However, pretreatment of patients with G-CSF with or without SCF did not enhance the retroviral infectability of growth factor-mobilized progenitor cells. The effect of the growth factor, Flk-2/Flt3 ligand (FL), was also examined with respect to retroviral transduction efficiency of human progenitor cells. FL plus IL-3 in vitro increased the retroviral transduction efficiency up to eightfold compared with results observed using other combinations of cytokines tested (P < .001). These findings have clinical implications both for increasing the number of target cells for in vivo gene-marking/gene-therapy studies and improving the efficiency of gene transfer. 相似文献
993.
M R Soules D K Clifton W J Bremner R A Steiner 《The Journal of clinical endocrinology and metabolism》1987,65(3):457-464
The pulse frequency of LH and FSH (and by inference, GnRH) is a major determinant of the relative baseline plasma levels of LH and FSH. Luteal phase deficiency has been reported to be associated with increased gonadotropin pulse frequency and inadequate preovulatory follicular development. In this study we induced in normal women a supraphysiological gonadotropin pulse frequency in the follicular phase to determine its effect on follicular development and corpus luteum function. Specifically, we tested the hypothesis that a supraphysiological GnRH pulse frequency would result in deficient luteal phase production of progesterone. The subjects were six normal ovulatory women (age range, 23-35 yr). They were initially studied during a control cycle (cycle 1). Then, 25 ng/kg GnRH was administered iv every 30 min from the early follicular phase of the next cycle (cycle 2) until ovulation occurred. GnRH administration resulted in increased follicular phase plasma LH and FSH levels and LH to FSH ratios, multiple preovulatory follicles (mean, 2.8) with increased mean integrated estradiol [1302 (pg/mL)day (cycle 1) vs. 2550 (pg/mL)day (cycle 2); P less than 0.05; 4780 vs. 9360 (pmol/L)day, Systeme International units], spontaneous ovulation, decreased luteal phase plasma immunoreactive and bioactive LH levels, decreased luteal phase length [13.5 days (cycle 1) vs. 8.8 days (cycle 2); P less than 0.05], and decreased mean integrated progesterone secretion [152 (ng/mL)day (cycle 1) vs. 66 (ng/mL)day (cycle 2); P less than 0.01; 482 vs. 209 (nmol/L)day, Systeme International units]. We conclude that high frequency LH and FSH secretion during the follicular phase can induce inadequate progesterone secretion during the subsequent luteal phase, and we infer that the pathophysiological basis for this induced luteal phase deficiency is decreased LH support of corpus luteum function. 相似文献
994.
Evaluation of the utility of the Vigileo FloTrac™, LiDCO™, USCOM and CardioQ™ to detect hypovolaemia in conscious volunteers: a proof of concept study 下载免费PDF全文
E. O'Loughlin M. Ward A. Crossley R. Hughes A. P. Bremner T. Corcoran 《Anaesthesia》2015,70(2):142-149
It is important to detect and treat hypovolaemia; however, detection is particularly challenging in the conscious, spontaneously breathing patient. Eight healthy male volunteers were monitored using four minimally invasive monitors: Vigileo FloTrac?; LiDCOrapid?; USCOM 1A; and CardioQ? oesophageal Doppler. Monitor output and clinical signs were recorded during incremental venesection of 2.5% estimated blood volume aliquots to a total of 20% blood volume removed. A statistically significant difference from baseline stroke volume was detected after 2.5% blood loss using the LiDCO (p = 0.007), 7.5% blood loss using the USCOM (p = 0.019), and 12.5% blood loss using the CardioQ (p = 0.046) and the FloTrac (p = 0.028). Receiver operator characteristic curves for predicting > 10% blood loss had areas under the curve of 0.68–0.82. The minimally invasive cardiac output devices tested can detect blood loss by a reduction in stroke volume in awake volunteers, and may have a role in guiding fluid replacement in conscious patients with suspected hypovolaemia. 相似文献
995.
Production of B cell growth factor(s) by neoplastic B cells from hairy cell leukemia patients 总被引:2,自引:0,他引:2
Recent studies have shown that normal human T cells contain a high- molecular-weight (mol wt) protein exhibiting B cell growth factor (BCGF) activity. Other studies have shown that virally transformed human B cells also secrete a high-mol-wt BCGF-like molecule in vitro. We have studied neoplastic B cells from patients with untreated hairy cell leukemia (HCL) to ascertain whether such cytoplasmic BCGF activity is present in the tumor cells. Studies on HCL cells from four patients indicated that BCGF-like activity was in fact present in the cytosolic extracts when tested on autochthonous HCL cells as well as on normal BCGF-dependent human B cell lines. Chromatographic analysis indicated that the BCGF activity from HCL cells was similar in mol wt as well as function to the normal T cell-derived cytosolic BCGF activity. These studies suggest that HCL cells contain and, in some cases, secrete a high-mol-wt growth factor that can be autostimulatory and appears to resemble a similar growth factor molecule found in normal human T cells. 相似文献
996.
K M Gross A M Matsumoto W J Bremner 《The Journal of clinical endocrinology and metabolism》1987,64(4):675-680
To test the hypothesis that the frequency of pulsatile LHRH stimulation can differentially control LH and FSH secretion in man, we administered low doses of LHRH in pulsatile fashion in several different regimens to men with idiopathic hypogonadotropic hypogonadism (IHH) and presumed endogenous LHRH deficiency. In study 1, four men with IHH received a constant amount of LHRH per day in three different frequencies. After an initial 7-day period of LHRH (5.0 micrograms every 2 h), the men received 2.5 micrograms every 1 h and 7.5 micrograms every 3 h, each for 4 days, in varying order. Frequent blood samples were obtained before LHRH administration and at the end of each regimen. Before LHRH administration, mean serum FSH and LH levels were low [28 +/- 3 (+/- SEM) and 6 +/- 2 ng/mL, respectively], and they increased into the normal adult male range during LHRH treatment. As the frequency of LHRH administration decreased from every 1 to 2 to 3 h, serum FSH levels progressively increased from 99 +/- 33 to 133 +/- 34 to 181 +/- 58 ng/mL (P less than 0.05). Serum LH levels (34 +/- 6, 33 +/- 6, and 34 +/- 5 ng/mL) were significantly higher than those before LHRH administration and did not differ significantly among the three regimens. Total serum testosterone (T), estradiol, and free T levels were increased by LHRH, but were not significantly different during the three regions of LHRH administration. In study 2, three men with IHH received the same amount of LHRH per dose, given in two different pulse frequencies; 2.5 micrograms LHRH were administered in frequencies of every 0.5 h and every 1.5 h, each for 4 days, in varying order. During the 0.5 h frequency, the mean serum FSH level was 42 +/- 13 ng/mL, and it rose to 80 +/- 19 ng/mL during the 1.5 h frequency (P less than 0.05). Corresponding mean serum LH levels were 25 +/- 5 and 27 +/- 4 ng/mL. Serum T and estradiol levels were not significantly different during the two LHRH regimens. We conclude that the frequency of LHRH stimulation can differentially control FSH and LH secretion by the human pituitary gland, and the pattern of hormonal stimulation may be a determinant of target organ response. 相似文献
997.
Testosterone (T) is not administered orally, because it has been reported to be rapidly metabolized by the liver. We hypothesized that sufficient doses of T or T enanthate (TE), administered orally in oil, would result in clinically useful elevations in serum T. We also hypothesized that coadministration of dutasteride (D) with T or TE would minimize increases in serum DHT seen previously with oral administration. Therefore, we conducted a pharmacokinetic study of oral T and TE in oil, with and without concomitant D, in normal men whose T production had been temporarily suppressed by the GnRH antagonist acyline. Thirteen healthy men (mean age, 24 +/- 6 yr) were enrolled and assigned to oral T (n = 7) and oral TE (n = 6) groups and were administered 200, 400, or 800 mg of either T or TE in sesame oil in the morning on 3 successive days 24 h after receiving acyline. Blood samples for measurement of serum T and dihydrotestosterone were obtained before T or TE administration and 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 h after administration. Subjects were then administered D for 4 d before repeating the sequence of T or TE doses with D. Serum T was significantly increased in a dose-dependent fashion with the administration of oral T or TE in oil. Coadministration of D with oral T or TE significantly increased the 24-hr average serum T levels compared with administration of T or TE alone [average serum T after 400 mg dose, 8.7 +/- 3.0 nmol/l (T) and 8.3 +/- 5.7 nmol/l (TE) vs. 16.1 +/- 5.8 nmol/l (T +D) and 15.0 +/- 8.8 nmol/l (TE + D); P < 0.05 for T vs. T and D]. The administration of oral T or TE in oil combined with D results in unexpected and potentially therapeutic increases in serum T. Additional studies of this combination as a novel form of oral androgen therapy are warranted. 相似文献
998.
KMI Salem OA Shannak BE Scammell CG Moran 《Annals of the Royal College of Surgeons of England》2014,96(6):446-451
Introduction
Dislocation following hip hemiarthroplasty (HHA), its incidence, predictors, treatment outcomes and mortality were investigated in a single centre series.Methods
The prospectively collected data on neck of femur fracture admissions compiled over 11 years were reviewed. Place of residence, place of fall, past medical history, intraoperative factors (grade of surgeon, delay in surgery, type of implant and operative time), postoperative complications and mortality were compared between patients who suffered a dislocation and those who did not. In the dislocation group, the mean number of dislocations, reduction method, type and fate of implant, and mortality were investigated.Results
Prospective data on 8,631 admissions were collected; 41% of these were managed with a HHA. The dislocation rate was 0.76%. A delay in surgery of >24 hours was associated with a fourfold increase in the dislocation risk. The majority (81%) of dislocations occurred in the first six weeks and closed manipulation was the definitive treatment in only 23% of the cases. The mortality rate was not increased following HHA dislocation.Conclusions
The delay in surgery was the most important predictor of HHA dislocation. Closed reduction was associated with a high failure rate. While an initial attempt at closed reduction for a first dislocation is recommended, for redislocators, we recommend early exploration/revision as an alternative to repeat manipulations. 相似文献999.
Promotion of estrogen-induced mammary gland carcinogenesis by androgen in the male Noble rat: probable mediation by steroid receptors 总被引:1,自引:0,他引:1
Both endogenous and exogenous estrogen exposure is associated with an
increased breast cancer risk. In some studies, elevated serum testosterone
levels have also been linked to an increased breast cancer risk. Estrogen
alone or combined with progesterone induces high mammary tumor incidences
in various strains of both male and female rats. Mammary gland ductal
adenocarcinomas were induced after 17beta- estradiol (E2) and testosterone
propionate (TP) treatment in male Noble rats. Tumor incidence was 100%
after 8-9 months of treatment. Such neoplasms were not detected after
either estrogen or androgen exposure alone within this time period. TP
alone caused disruption of mammary gland ducts and proliferation of stromal
tissue, while E2 treatment alone induced both ductal epithelial growth and
nodular atypical hyperplasia. To study the interaction of these hormones in
mammary tumorigenesis, sex hormone receptors were characterized in mammary
glands of Noble rats. Estrogen receptor-alpha (ER) was detected in age-
matched, untreated mammary gland epithelium; in most early atypical
hyperplastic lesions appearing after E2 and E2 + TP treatment and in E2 +
TP-induced mammary tumors. Two major ER putative isoforms, 116 and 120 kDa,
were detected in E2- and E2 + TP-treated mammary glands, and in the induced
tumors. A 54 kDa ER protein was found in untreated and TP-treated mammary
glands, and in the induced tumors. Both progesterone receptor-B (PR-B) and
PR-A2, as well as androgen receptor-B (AR-B) and AR-A isoforms were
markedly elevated in all E2 + TP-induced mammary tumors. However, the
levels of both PR and AR were very low in mammary glands of E2- and E2 +
TP-treated male rats. Low and moderate levels of AR and PR, respectively,
were detected in most atypical hyperplastic lesions induced by E2- and E2 +
TP-treated mammary glands. These results suggest that androgens may
interact with either AR or PR, and perhaps both receptors, in E2 +
TP-induced mammary glands and the induced tumors to effect the reduction in
latency period, enhance tumor size, and increase incidence to 100%.
相似文献
1000.
Telomerase reverse transcriptase expression is increased early in the Barrett’s metaplasia, dysplasia, adenocarcinoma sequence 总被引:18,自引:2,他引:16
Reginald V. N. Lord F.R.A.C.S. Dennis Salonga B.S. Kathleen D. Danenberg M.S. Jeffrey H. Peters M.D. Tom R. DeMeester M.D. Ji Min Park B.S. Jan Johansson M.D. Kristin A. Skinner M.D. Para Chandrasoma M.D. Steven R. DeMeester M.D. Cedric G. Bremner M.Ch. Peter I. Tsai M.D. Peter V. Danenberg Ph.D. 《Journal of gastrointestinal surgery》2000,4(2):135-142