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991.
R Jokic A Klimaszewski G Sridhar MF Fitzpatrick 《Canadian Metallurgical Quarterly》1998,114(4):1061-1069
OBJECTIVES: (1) To compare the continuous positive airway pressure (CPAP) requirement at the time of diagnosis (T0), after 2 weeks (T2), and after 4 weeks (T4) of CPAP treatment, in patients with severe obstructive sleep apnea (OSA); and (2) to assess whether any alteration in CPAP requirement over the first 4 weeks of CPAP treatment would influence daytime alertness, subjective sleepiness, or mood. DESIGN: A prospective, controlled, single-blind crossover study. SETTING: University teaching hospital. PATIENTS: Ten patients with newly diagnosed and previously untreated severe OSA (aged 52+/-9 years, apnea hypopnea index [AHI] of 99+/-31) and subsequently 10 control patients (aged 52+/-11 years, AHI 85+/-17). MEASUREMENTS: Overnight polysomnography with CPAP titration to determine the CPAP requirement, which was standardized for body position and sleep stage, on all three occasions (T0, T2, T4). Objective sleep quality, daytime alertness, subjective sleepiness (Epworth Sleepiness Scale), and mood (Hospital Anxiety and Depression Scale). RESULTS: CPAP requirement decreased from T0 to T2 (median difference, 1.5 cm H2O, 95% confidence interval [CI], 1.1 to 2.7 cm H2O, p=0.0004) and did not differ between T2 and T4. Use of the lower CPAP pressure during T2 to T4 was associated with a decrease in Epworth scale (mean difference, 2.6, 95% CI, 1.2 to 4; p=0.01) and anxiety (median change, 2; 95% CI, 0.5 to 2.9, p=0.03) scores, as compared with the first 2 weeks. Daytime alertness did not differ between T0 to T2 and T2 to T4. CONCLUSION: CPAP requirement falls within 2 weeks of starting CPAP treatment. A change to the lower required CPAP was not associated with any deterioration in daytime alertness but was associated with small subjective improvements in sleepiness and mood. 相似文献
992.
K Maskos C Fernandez-Catalan R Huber GP Bourenkov H Bartunik GA Ellestad P Reddy MF Wolfson CT Rauch BJ Castner R Davis HR Clarke M Petersen JN Fitzner DP Cerretti CJ March RJ Paxton RA Black W Bode 《Canadian Metallurgical Quarterly》1998,95(7):3408-3412
Tumor necrosis factor-alpha (TNFalpha) is a cytokine that induces protective inflammatory reactions and kills tumor cells but also causes severe damage when produced in excess, as in rheumatoid arthritis and septic shock. Soluble TNFalpha is released from its membrane-bound precursor by a membrane-anchored proteinase, recently identified as a multidomain metalloproteinase called TNFalpha-converting enzyme or TACE. We have cocrystallized the catalytic domain of TACE with a hydroxamic acid inhibitor and have solved its 2.0 A crystal structure. This structure reveals a polypeptide fold and a catalytic zinc environment resembling that of the snake venom metalloproteinases, identifying TACE as a member of the adamalysin/ADAM family. However, a number of large insertion loops generate unique surface features. The pro-TNFalpha cleavage site fits to the active site of TACE but seems also to be determined by its position relative to the base of the compact trimeric TNFalpha cone. The active-site cleft of TACE shares properties with the matrix metalloproteinases but exhibits unique features such as a deep S3' pocket merging with the S1' specificity pocket below the surface. The structure thus opens a different approach toward the design of specific synthetic TACE inhibitors, which could act as effective therapeutic agents in vivo to modulate TNFalpha-induced pathophysiological effects, and might also help to control related shedding processes. 相似文献
993.
G Lenzen F Pietri-Rouxel MF Drumare A Amiard S Guillot P Archimbault AD Strosberg 《Canadian Metallurgical Quarterly》1998,363(2-3):217-227
A molecular clone encoding a beta3-adrenoceptor was isolated from a canine genomic library. The cloned receptor exhibited a pharmacological profile similar to that of other species: in particular, high efficiency of the two selective beta3-adrenoceptor agonists, CL 316,243 (disodium(R,R)-5[2[[2-(chlorophenyl)-2hydroxyethyl]-amino]propyl]- 1,3-benzodioxole-2,2-dicarboxylate) and ICI 201651 ((R)4-(2-hydroxy-3-phenoxypropylaminoethoxy)-N-(2-methoxyethyl)phe noxy acetic acid) and a low affinity for the radioligand (-)-[3-(125)I]-iodocyanopindolol. Interestingly, CGP 12177A ((+/-)-4-(3-t-butylamino-2-hydroxypropoxy)benzimidazol-2-one), which is described as a partial agonist for the human receptor, was a full agonist for the canine receptor. After expression and stimulation of the canine beta3-adrenoceptor in stably transfected Chinese hamster ovary cells there was a very low accumulation of cAMP, suggesting weak coupling to Gs-protein and adenylyl cyclase. However, the response was much better in human embryonal kidney cells transfected with the canine beta3-adrenoceptor gene. The cloning of the canine beta3-adrenoceptor and the insights gained from its pharmacological characterization may allow the development of selective compounds for use in the treatment of obese dogs. 相似文献
994.
The syndrome of vacuous chewing movements (VCMs) in rats is similar in many respects to tardive dyskinesia (TD) in humans. Both syndromes are characterized by delayed onset of persistent orofacial dyskinesias in a sub-group of subjects chronically treated with neuroleptics. Using the rat model, we examined the role of NMDA receptor-mediated corticostriatal neurotransmission in the expression of VCMs. Rats were treated for 36 weeks with haloperidol decanoate or vehicle and then withdrawn for an additional 28 weeks. Chronic persistent VCMs were induced in one subgroup of treated animals (+VCM), but not in another group (-VCM). Rats from +VCM, -VCM groups and vehicle-treated controls were selected for post mortem studies (n = 12 to 14 per group). NMDA receptor levels were assessed using [3H]-MK-801 binding in sections from the mid-striatum and nucleus accumbens. Chronic haloperidol treatment produced a marked reduction of NMDA receptor binding levels throughout the striatum and nucleus accumbens. Post hoc comparisons demonstrated that -VCM rats had lower NMDA receptor binding levels than +VCM and vehicle-treated controls. Ventromedial striatum and nucleus accumbens core were the most affected areas. These findings suggest that down-regulation of striatal NMDA receptor binding levels may protect against the expression of neuroleptic-induced dyskinesia. 相似文献
995.
996.
DP Edward MF Mafee E Garcia-Valenzuela RA Weiss 《Canadian Metallurgical Quarterly》1998,36(6):1119-31, x
Coats' disease is an idiopathic disorder in which telangiectatic and aneurysmal retinal vessels leak a lipoproteinaceous exudate, with consequent bullous retinal detachment. It is a diagnostic challenge, and CT and MR imaging provide valuable information to differentiate it from other pathologies, particularly from retinoblastoma. Typical, advanced Coats' disease shows on CT a denser substance posterior to the vitreous, which on MR is hyperintense on all pulse sequences. Contrast administration on both CT and MR might give slight linear enhancement at the boundary between vitreous and exudation. Persistent hyperplastic primary vitreous (PHPV) is a unilateral disorder in a microphthalmic eye, seen in full-term infants. PHPV rarely is bilateral in patients with Norrie's disease, Warburg syndrome, or patients with retinal dysplasia. Persistent fetal vasculature leads to fibrosis, resulting in elongation of the ciliary processes, retinal detachment, and spontaneous cataracts. The CT appearance in the disorder is quite variable; however, MR imaging may be superior in demonstrating the enhancing retrolental mass and the elongated ciliary processes. 相似文献
997.
MF Dealy 《Canadian Metallurgical Quarterly》1998,23(5):12-3, 16, 18-20 passim; quiz 24-5
Dysfunctional uterine bleeding is a common complaint in adolescent girls. Clinicians working in pediatric, internal medicine, and gynecology offices and in emergency departments are often called upon to make this diagnosis. Dysfunctional bleeding is defined as irregular, painless bleeding of endometrial origin that may be excessive, prolonged, or unpatterned. Although the bleeding is usually secondary to anovulation, the diagnosis is one of exclusion. To make an accurate diagnosis, the clinician must understand the normal adolescent menstrual cycle and related hormone feedback mechanisms. This article reviews the normal hormone mechanisms in the adult and adolescent menstrual cycles in an effort to guide the clinician through the diagnosis. Potential causes and recommended treatment modalities are reviewed. 相似文献
998.
Oral submucous fibrosis (OSF) is a chronic fibrotic disease of the oral cavity and oropharynx characterized by fibroelastic change in the mucosa which leads to progressive inability to open the mouth. The inflammatory cells in the lesional tissue consist mainly of T lymphocytes, with a high CD4:CD8 ratio, and major histocompatibility complex (MHC) class II expressing antigen-presenting cells. Cytokines and growth factors produced by inflammatory cells within the lesion may promote fibrosis by inducing proliferation of fibroblasts, upregulating collagen synthesis and downregulating collagenase production. The authors used a three-stage immunoperoxidase technique to investigate the expression of interleukin alpha (IL-1alpha) and beta, IL-6 interferon (IFN)-alpha, beta and gamma, transforming growth factor beta (TGF-beta), platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) in frozen sections of OSF and compared it with that in normal buccal mucosa. The expression of cytokines and growth factors in normal tissues was consistent with their well known distribution and cell of origin, but the intensity and distribution in OSF were all, with the exception of IFN-alpha and gamma, upregulated with strong expression in both the epithelium and underlying connective tissue. IFN-alpha showed a similar pattern of staining in both normal mucosa and OSF. IFN-gamma showed little or no expression in most lesional tissues, suggesting an innate deficiency or downregulation of this cytokine. The general increase in pro-inflammatory cytokines and growth factors, and reduced production of IFN-gamma, may play an important role in the pathogenesis of OSF. 相似文献
999.
CM Almeida MM Kanashiro FB Rangel Filho MF Mata TL Kipnis WD da Silva 《Canadian Metallurgical Quarterly》1998,143(21):579-584
Adult white leghorn hens hyperimmunised with Brazilian snake venoms of the genus Bothrops and/or Crotalus produced antibodies capable of recognising, combining with and neutralising the toxic and lethal components of the venoms. The antibodies were first detected by an enzyme-linked immunosorbent assay two weeks after starting the immunisation schedule, reached the highest titres by the third week and remained high for at least 24 weeks. These antibodies are transferred to the egg yolk from which they were isolated as enriched IgY preparations by a combination of methods using positive and negative precipitation with sodium sulphate and/or caprylic acid. The yolk-derived IgY preparations contained antibodies which blocked the phospholipase A2-dependent haemolytic activity of both venoms and the haemorrhagic activity of Bothrops venom, and neutralised the toxic lethal activities of the venoms with good efficacy. The median effective dose (ED50) of the IgY anti-Bothrops venom was 592.5 microliters/2LD50 and, 1.0 ml neutralised 0.0675 mg of venom. The ED50 of the IgY anti-Crotalus venom was 457.5 microliters/3LD50 and 1.0 ml neutralised 0.075 mg of venom. 相似文献
1000.
Sentences were processed through simulations of cochlear-implant signal processors with 6, 8, 12, 16, and 20 channels and were presented to normal-hearing listeners at +2 db S/N and at -2 db S/N. The signal-processing operations included bandpass filtering, rectification, and smoothing of the signal in each band, estimation of the rms energy of the signal in each band (computed every 4 ms), and generation of sinusoids with frequencies equal to the center frequencies of the bands and amplitudes equal to the rms levels in each band. The sinusoids were summed and presented to listeners for identification. At issue was the number of channels necessary to reach maximum performance on tests of sentence understanding. At +2 dB S/N, the performance maximum was reached with 12 channels of stimulation. At -2 dB S/N, the performance maximum was reached with 20 channels of stimulation. These results, in combination with the outcome that in quiet, asymptotic performance is reached with five channels of stimulation, demonstrate that more channels are needed in noise than in quiet to reach a high level of sentence understanding and that, as the S/N becomes poorer, more channels are needed to achieve a given level of performance. 相似文献