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951.
Booij LH van der Broek LA Caulfield W Dommerholt-Caris BM Clark JK van Egmond J McGuire R Muir AW Ottenheijm HC Rees DC 《Journal of medicinal chemistry》2000,43(25):4822-4833
Herein we describe the synthesis of novel di- and tripeptide derivatives with two quaternary nitrogen groups attached and the biological testing of these compounds for neuromuscular blocking (NMB) activity in vitro and in vivo. The short peptide scaffold was selected because it offers potential for desired distance between the two pharmacophoric quaternary nitrogen groups, short duration of action, straightforward synthesis, and compatibility with an injectable formulation. From a small series of compounds 20c,e are identified as effective non-depolarizing NMB agents in vitro and in vivo in anesthetized cats and Rhesus monkeys with potencies similar to those of the clinical reference compounds rocuronium (4) and suxamethonium (2) (monkey ED(90) = 0.68, 0.23, 0.16, 5.04 micromol/kg, respectively). These new peptide derivatives 20c,e have similar potency and onset time but longer duration and slower recovery than the clinically used reference compounds. The structure-activity relationships described for this chemical series lead to the conclusion that the di- or tripeptide fragment can be regarded as an alternative template to the steroid or aliphatic ester of previously reported NMBs and within this tripeptide-derived series clog P correlates well with in vitro NMB activity. 相似文献
952.
Enterocystoplasty or detrusor myectomy? Comparison of indications and outcomes for bladder augmentation 总被引:3,自引:0,他引:3
PURPOSE: We review our experience with enterocystoplasty and detrusor myectomy to delineate clinical indications and compare operative outcomes with both types of bladder augmentation. MATERIALS AND METHODS: Retrospective analysis of 61 patients who had undergone a total of 37 detrusor myectomies and 32 enterocystoplasties was performed. The patients were categorized into 6 diagnostic subsets representative of the clinical spectrum of indications for bladder augmentation. RESULTS: For most clinical indications detrusor myectomy offered comparable success or significant improvement in bladder function without incurring the significant complication rate of enterocystoplasty. CONCLUSIONS: Detrusor myectomy is a safe, successful method of bladder augmentation for most clinical indications. Myectomy does not hinder subsequent creation of an enterocystoplasty. 相似文献
953.
Fleming GF Roth BJ Baker SD Sutton GP Look KY Muggia FM Fracasso PM McGuire WP 《American journal of clinical oncology》2000,23(6):609-613
A phase I study was performed to determine the maximum tolerated doses of intravenous etoposide and paclitaxel for women with previously treated persistent or recurrent ovarian cancer. Starting doses were paclitaxel 135 mg/m2 during 24 hours and etoposide 50 mg/m2/day for 3 consecutive days. The study was designed to escalate first the dose of etoposide, and then the dose of paclitaxel, in successive cohorts of patients. In an attempt to determine whether toxicity was affected by sequence of the drugs, the order of administration of the two drugs was reversed on alternate cycles. The starting doses of paclitaxel (135 mg/m2/24 hours) and etoposide (50 mg/m2/day x 3) caused severe neutropenia even with the addition of granulocyte colony-stimulating factor, and the trial was amended to administer the paclitaxel during 3 hours. However, this also proved too myelosuppressive without growth factor support. Twenty-one women were treated. A complete response was observed in one of nine patients with measurable disease, and a major decrease in CA-125 was noted in two patients who did not have measurable disease. Because of the severe myelosuppression observed in most patients, dose reduction was often required after the first cycle. The power to detect sequence-dependent variation in toxicity was minimal; however, no large differences were observed. A combination of the usual doses of these drugs will be difficult to administer in patients who have received previous chemotherapy for ovarian cancer. 相似文献
954.
955.
McGuire JR Harvey RL 《Physical medicine and rehabilitation clinics of North America》1999,10(4):857-74, ix
Medical, neurologic, and psychiatric complications can interfere with optimal recovery after stroke and increase the cost of care. Ideally, preventing these complications would be the best and most cost-effective treatment. This article reviews the clinical implications and management strategies for venous thromboembolism, spasticity, and depression after stroke. 相似文献
956.
Vaccination remains a vital strategy in the prevention of infectious disease. Commercial vaccine formulations contain a range of additives or manufacturing residuals, which may contribute to patient concerns about vaccine safety. Primary health care professionals are well placed to address patient concerns about vaccine safety. We describe the key constituents present in vaccines, discuss issues related to safety and acceptability of these constituents, and provide a table highlighting constituents of commercially available vaccines in Australia. 相似文献
957.
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959.
McGuire SO Sortwell CE Shukitt-Hale B Joseph JA Hejna MJ Collier TJ 《Nutritional neuroscience》2006,9(5-6):251-258
The exact mechanisms contributing to poor neuronal survival in cell transplantation paradigms for Parkinson's disease (PD) are unknown. However, transplantation-induced host immune response, inflammation, and subsequent oxidative stress are likely contributors to cell death since dopamine (DA) neurons are exquisitely sensitive to oxidative damage. Multiple studies have attempted to improve cell survival by treating transplant material with antioxidant and antiinflammatory compounds, whereas far fewer studies have attempted to modify the host environment to reduce these threats. Flavonoids, phytochemicals found in fruits and vegetables, have antioxidant, antiinflammatory, and immunomodulatory properties. For example, supplementation with dietary blueberry extract (BBE) prevents oxidative stress-associated impairment of striatal motor function during aging and restores lost motor function in aged rats. We hypothesized that dietary supplementation of rodent diets with BBE would improve the survival of embryonic DA neurons transplanted into the unilaterally DA-depleted striatum. Inclusion of 2% BBE in a custom chow diet significantly increased the survival of implanted DA neurons and ameliorated rotational behavior asymmetries as compared to transplanted animals consuming a standard diet. These findings provide support for the potential of dietary phytochemicals as an easily administered and well-tolerated therapy that can be used to improve the effectiveness of DA neuron replacement. 相似文献
960.
Parekh SG Sodha S McGuire KJ Bozentka DJ Rozental TD Beredjiklian PK 《Clinical orthopaedics and related research》2004,(421):54-59
The Internet has become an important source of medical information for patients. However, the availability of this resource for individuals in the lower socioeconomic groups is limited, a concept termed the digital divide. To evaluate this phenomenon, we conducted a survey study to quantify the accessibility and use of the Internet for obtaining medical information in an outpatient hand surgery clinic population. A 28-question survey was distributed to 207 patients concerning computer accessibility, Internet use for medical and nonmedical information, Internet trust and security, and patient economic demographics. After analysis of the data, we found individuals in households with higher incomes had a greater likelihood of owning computers than those in lower income brackets. As income increases, the time spent on the Internet also increases. Another statistically significant trend was that higher income patient households thought that Internet information was trustworthy, secure, and private compared with the lower income brackets. We concluded that clinical settings where the predominant patient population earns less than $18,000 may not benefit or use physician Internet-based services or information. The concept of the digital divide seems to be a real phenomenon in the clinical practice of orthopaedics. 相似文献