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Effectiveness of exercise in patients with osteoarthritis of hip or knee: nine months' follow up

ANNALS OF THE RHEUMATIC DISEASES 2001年第12期60卷 1123-1130页

作者： van Baar, ME Dekker, J Oostendorp, RAB Bijl, D Voorn, TB Bijlsma, JWJ Netherlands Inst Primary Hlth Care NL-3500 BN Utrecht Netherlands Vrije Univ Amsterdam Inst Res Extramural Med Amsterdam Netherlands Dutch Natl Inst Allied Hlth Profess Amersfoort Netherlands Univ Utrecht Dept Gen Practice Utrecht Netherlands Univ Utrecht Hosp Dept Rheumatol & Immunol NL-3584 CX Utrecht Netherlands

Objective-To determine whether the effects of an exercise programme in patients with osteoarthritis of hip or knee are sustained at six and nine months' follow up. Methods-A randomised, single blind, clinical trial was conducted in a primary care setting. Patients with osteoarthritis of hip or knee (ACR criteria) were selected. Two intervention groups were compared. Both groups received treatment from their general practitioner, including patient education and drug treatment if necessary. The experimental group also received exercise treatment from a physiotherapist in primary care. The treatment period was 12 weeks, with an ensuing 24 week follow up. The main outcome measures were pain, drug use (non-steroidal anti-inflammatory drugs), and observed disability. Results-201 patients were randomly allocated to the exercise or control group, and 183 patients completed the trial. At 24 weeks exercise treatment was associated with a small to moderate effect on pain during the past week (difference in change between the two groups -11.5 (95% CI -19.7 to -3.3). At 36 weeks no differences were found between the groups. Conclusions-Beneficial effects of exercise decline over time and finally disappear.

关键词：消炎药非甾类/投药和剂量综合疗法用药计划表运动疗法/方法随访研究骨关节炎髋/药物疗法骨关节炎髋/病理生理学骨关节炎髋/康复骨关节炎膝/药物疗法骨关节炎膝/病理生理学骨关节炎膝/康复预后活动范围关节单盲法治疗结果老年人女(雌)性人类男(雄)性中年人

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EFFICACY AND SAFETY OF NEDOCROMIL SODIUM OPHTHALMIC SOLUTION IN THE TREATMENT OF SEASONAL ALLERGIC CONJUNCTIVITIS

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AMERICAN JOURNAL OF OPHTHALMOLOGY 1992年第1期113卷 56-63页

作者： BLUMENTHAL, M CASALE, T DOCKHORN, R JARMOSZUK, I KAISER, H SMITH, R ZEITZ, HJ GRANT HOSP MAX SAMTER INST ALLERGY & CLIN IMMUNOLCHICAGOIL UNIV MINNESOTA DEPT MEDMINNEAPOLISMN 55455 UNIV IOWA HOSP & CLIN DEPT INTERNAL MEDIOWA CITYIA 52242 GRANT HOSP CLIN RES UNITCHICAGOIL UNIV KANSAS SCH MEDDEPT MEDPRAIRIE VILLAGEKS

To assess the efficacy and safety of twice-daily administration of nedocromil sodium 2% ophthalmic solution, we performed a multicenter study involving 140 patients with seasonal allergic conjunctivitis. Subjects had a history of seasonal allergic conjunctivitis and positive results of a skin test to ragweed. The trial coincided with the peak ragweed pollen season at five treatment centers. Patients treated with nedocromil sodium had improvements in symptoms with statistically significant reductions recorded for eye itching (P less-than-or-equal-to .04), conjunctival injection (P less-than-or-equal-to .001), and overall disease severity (P less-than-or-equal-to .001) as compared to the placebo-treated group. Adverse events were minor and transient. We concluded that nedocromil sodium 2% ophthalmic solution administered twice daily is effective in relieving major symptoms associated with seasonal allergic conjunctivitis.

关键词：结膜炎变应性/药物疗法用药计划表药物评价奈多罗米眼药水喹诺酮类/投药和剂量儿童女(雌)性人类男(雄)性中年人

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 1999年第5期33卷 1174-1181页

作者： Havranek, EP Thomas, I Smith, WB Ponce, GA Bilsker, M Munger, MA Wolf, RA Univ Colorado Denver Hlth Med Ctr 0960 Hlth Sci Ctr Denver CO 80204 USA Slidell Mem Hosp Slidell LA USA Louisiana Cardiovasc Res Ctr New Orleans LA USA Adult Cardiovasc Dis Hernet CA USA Univ Miami Sch Med Miami FL USA Univ Utah Heart Failure Treatment Program Salt Lake City UT 84112 USA Bristol Myers Squibb Princeton NJ USA

OBJECTIVES The primary purpose of this study was to determine the acute and long-term hemodynamic and clinical effects of irbesartan in patients with heart failure. BACKGROUND Inhibition of angiotensin II production by angiotensin-converting enzyme (ACE) inhibitors reduces morbidity and mortality in patients with heart failure. Irbesartan is an orally active antagonist of the angiotensin II AT, receptor subtype with potential efficacy in heart failure. METHODS Two hundred eighteen patients with symptomatic heart failure (New York Heart Association [NYHA] class II-IV) and left ventricular ejection fraction less than or equal to 40% participated in the study. Serial hemodynamic measurements were made over 24 h following randomization to irbesartan 12.5 mg, 37.5 mg, 75 mg, 150 mg or placebo. After the first dose of study medication, patients receiving placebo were reallocated to one of the four irbesartan doses, treatment was continued for 12 weeks and hemodynamic measurements were repeated. RESULTS Irbesartan induced significant dose-related decreases in pulmonary capillary wedge pressure (average change -5.9 +/- 0.9 mm Hg and -5.3 +/- 0.9 mm Hg for irbesartan 75 mg and 150 mg, respectively) after 12 weeks of therapy without causing reflex tachycardia and without increasing plasma norepinephrine. The neurohormonal effects of irbesartan were highly variable and none of the changes was statistically significant. There was a significant dose-related decrease in the percentage of patients discontinuing study medication because of worsening heart failure. Irbesartan was well tolerated without evidence of dose-related cough or azotemia. CONCLUSIONS Irbesartan, at once-daily doses of 75 mg and 150 mg, induced sustained hemodynamic improvement and prevented worsening heart failure. (C) 1999 by the American College of Cardiology.

关键词：血管紧张素受体拮抗剂抗高血压药/投药和剂量抗高血压药/治疗应用联苯化合物/投药和剂量联苯化合物/治疗应用剂量效应关系药物双盲法用药计划表随访研究心力衰竭/血液心力衰竭/药物疗法心力衰竭/病理生理学血流动力学/药物作用去甲肾上腺素/血液受体血管紧张素 1型受体血管紧张素 2型安全单盲法四唑类/投药和剂量四唑类/治疗应用治疗结果青少年成年人女(雌)性人类男(雄)性中年人

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A randomized trial measuring fecal blood loss after treatment with rofecoxib, ibuprofen, or placebo in healthy subjects

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AMERICAN JOURNAL OF MEDICINE 2000年第3期109卷 201-206页

作者： Hunt, RH Bowen, B Mortensen, ER Simon, TJ James, C Cagliola, A Quan, H Bolognese, JA Merck Res Labs West Point PA 19486 USA McMaster Univ Hamilton ON Canada Univ Toronto Toronto ON Canada

PURPOSE: Gastrointestinal microbleeding, as assessed by the measurement of (51)chromium-labeled red blood cells, is a marker of the mucosal injury associated with the use of nonsteroidal anti-inflammatory drugs. This study tested the hypotheses that cyclooxygenase-2 specific inhibition with rofecoxib would cause less fecal blood loss than a therapeutic dose of ibuprofen and would be equivalent to placebo. SUBJECTS AND METHODS: In this randomized, double-blind group study, gastrointestinal blood loss was assessed by measurement of fecal (51)chromium radioactivity during a 1-week placebo baseline period and during 4 weeks of treatment with rofecoxib) (25 mg or 50 mg once daily), ibuprofen (800 mg three times daily), or placebo in 67 healthy subjects. Gastrointestinal blood loss during treatment weeks 2 to 4 (versus the baseline period) was expressed as the geometric mean ratio of fecal radioactivity in weeks 2 to 4 compared with baseline. RESULTS: Ibuprofen caused significantly (P <0.001) greater gastrointestinal blood loss (geometric mean ratio of 5.2, 95% confidence interval [CI]: 4.2 to 6.3) than the 25-mg dose of rofecoxib (2.6, 95% CI: 2.2 to 3.1), the 50-mg dose of rofecoxib (2.6, 95% CI: 2.2 to 3.0), or placebo (2.1, 95% CI: 1.8 to 2.5). In contrast, gastrointestinal blood loss with both doses of rofecoxib were equivalent to placebo by a predetermined clinical similarity bound. CONCLUSIONS: In healthy subjects, treatment with rofecoxib, at 2 to 4 times the doses that are currently recommended for the treatment of patients with osteoarthritis, produced significantly less fecal blood loss than a therapeutic dose of ibuprofen and was equivalent to placebo. (C) 2000 by Excerpta Medica, Inc.

关键词：铬放射性同位素/诊断应用环氧化酶2 环氧化酶2抑制剂环加氧酶抑制药/投药和剂量双盲法用药计划表红细胞/放射性核素显像胃肠出血/化学诱导胃肠出血/放射性核素显像布洛芬/投药和剂量同工酶类/拮抗剂和抑制剂内酯类/投药和剂量膜蛋白质类潜血骨关节炎/药物疗法前列腺素内过氧化物合酶类放射性药物/诊断应用参考值砜类治疗结果人类男(雄)性中年人

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The neurochemical basis for the behavioral effects of Triadimefon

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NEUROBIOLOGICAL MECHANISMS OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES 2000年第1期914卷 336-353页

作者： Hill, D Ikaiddi, M Mazzio, E Soliman, KFA Florida A&M Univ Coll Pharm & Pharmaceut Sci Tallahassee FL 32307 USA

Administration of triadimefon (TDF) [1-(4-chlorophenoxy)-3,3-dimethyl-1-(1-H-1,2,4-triazol-1-yl)-2-butanone] in rodents incites heightened locomotor and stereotypy response, primarily through potentiation of dopaminergic activity. In the present study, 8 male Sprague-Dawley rats received repeated injections, on alternate days (100 mg/kg, 14 days) of TDF or corn oil. Enhanced locomotor and stereotypy behavioral patterns occurred in response to TDF injections, lasting until the 12th day of injection. Tolerance to this effect was evident by a lack of response to TDF injection by the 14(th) day. Similarly, a withdrawal period and challenge dose of TDF (5 days, 25 mg/kg) was ineffective in espousing locomotor or stereotypy behavioral changes. Cross sensitization to cocaine was also evident, since withdrawal and a challenge dose (8 days, 5 mg/kg) was also ineffective. Adaptative biochemical changes in dopaminergic function were examined after both acute (100 nl kg) and repeated administration of TDF (100 mg/kg, 14 days) by examining [H-3] dopamine (DA) uptake and DA release in both striatal (ST) and nucleus accumbens (NA) tissue. In corroboration with behavioral pattern indicating development of tolerance, there were significant changes in dopaminergic function. Repeated TDF exposure in vivo resulted in significant attenuation of ST and NA DA uptake in response to TDF (10(-4) to 10(-7) M) or cocaine (10(-5) to 10(-8) M) in vitro. Acute exposure to TDF in vivo also attenuated ST DA inhibitory effects of cocaine and TDF. Repetitive administration of TDF in vivo had no effect on in vitro TDF- or amphetamine-stimulated release of ST or NA DA. However, there was a significant reduction in amphetamine-stimulated DA release in animals after acute exposure to TDF in vivo. It was concluded from this study that the effects of chronic TDF exposure may primarily involve effects on DA uptake in the ST and NA.

关键词：苯丙胺/药理学行为动物/药物作用脑化学/药物作用可卡因/药理学纹状体/药物作用纹状体/代谢多巴胺/代谢多巴胺摄取抑制剂/药理学剂量效应关系药物用药计划表药物相互作用运动活动/药物作用伏核/药物作用伏核/代谢大鼠 Sprague-Dawley 刻板行为/药物作用时间因素三唑类/投药和剂量氚/代谢动物男(雄)性大鼠

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PHARMACOKINETIC RATIONALE FOR A MALARIAL SUPPRESSANT ADMINISTERED ONCE MONTHLY

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ANNALS OF TROPICAL MEDICINE AND PARASITOLOGY 1975年第2期69卷 141-146页

作者： PECK, CC LEWIS, AN JOYCE, BE LETTERMAN GEN HOSP SAN FRANCISCOCA 94129 UNIV CALIF INT CTR MED RESMED CTRSAN FRANCISCOCA 94102

Click to increase image sizeClick to decrease image size

关键词：剂型剂量效应关系药物用药计划表药物评价药物疗法联合叶酸拮抗剂/治疗应用半衰期印度疟疾/血液疟疾/药物疗法马来西亚/人种学乙胺嘧啶/血液乙胺嘧啶/药理学乙胺嘧啶/治疗应用磺胺多辛/血液磺胺多辛/药理学磺胺多辛/治疗应用氨苯磺胺类/药理学青少年成年人人类男(雄)性

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Prevention of heterotopic ossification in hip arthroplasty - The influence of the duration of treatment

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INTERNATIONAL ORTHOPAEDICS 1999年第2期23卷 107-110页

作者： Vastel, L Kerboull, L Dejean, O Courpied, JP Kerboull, M Hop Cochin Serv Chirurg Orthoped F-75674 Paris 14 France

A retrospective study has been carried out to assess the effectiveness of indomethacin in preventing heterotopic ossification after total hip arthroplasty, and the effect of using it for different periods of time. One hundred and sixty-eight hips operated on in 1983 were not given indomethacin and acted as a control. One hundred and fifty hips operated on in 1988 were given indomethacin and divided into 3 groups: 42 received indomethacin for 5 days, 49 for 11 days and 59 for 45 days. The results indicate that ossification is significantly reduced in those patients receiving indomethacin for 5 and 11 days, but there was no additional reduction when it was given for 45 days. Treatment should begin on the night of operation and continued for 11 days while the patient remains in hospital.

关键词：消炎药非甾类/投药和剂量关节成形术置换髋/副作用用药计划表发病率吲哚美辛/投药和剂量骨化异位性/诊断显像骨化异位性/病因学骨化异位性/预防和控制放射摄影术回顾性研究时间因素治疗结果老年人女(雌)性人类男(雄)性中年人

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Sildenafil citrate and blood-pressure-lowering drugs: Results of drug interaction studies with an organic nitrate and a calcium antagonist

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AMERICAN JOURNAL OF CARDIOLOGY 1999年第5A期83卷 21C-28C页

作者： Webb, DJ Freestone, S Allen, MJ Muirhead, GJ Univ Edinburgh Dept Med Sci Edinburgh Midlothian Scotland Inveresk Clin Res Edinburgh Midlothian Scotland Pfizer Cent Res Sandwich Kent England

Sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), is a well-tolerated and highly effective treatment for erectile dysfunction. The mechanism of action of sildenafil depends on activation of the nitric oxide (NO)cGMP pathway during sexual stimulation, which results In corpus cavernosal smooth muscle relaxation and penile erection. Endogenously derived NO is also involved in blood pressure regulation through its effect on basal vascular tone, which is mediated by cGMP levels. Organic nitrates and NO donors exert their therapeutic effects on blood pressure and vascular smooth muscle by the same mechanism as endogenous NO. Since both sildenafil and organic nitrates exert their pharmacologic effects via increases in cGMP concentrations, a double-blind, placebo-controlled, crossover study was undertaken to investigate the effects of sildenafil coadministered with glyceryl trinitrate on blood pressure and heart rate in healthy male subjects. The hemodynamic effects of sildenafil were also evaluated in a second placebo-controlled crossover study in men with hypertension who were taking the calcium antagonist amlodipine, which has a mechanism of action that does not involve the cGMP pathway. In the first crossover study, subjects were treated with oral sildenafil (25 mg, 3 times a day for 4 days) or placebo and then challenged on day 4 with a 40-minute, stepwise, intravenous infusion of glyceryl trinitrate (0.5 mg/mL in 5% dextrose at an initial infusion rate of 2.5 mu g/min and doubling every 5 minutes to a maximum rate of 40 mu g/min) 1 hour after taking sildenafil or placebo. On day 5, subjects received a sublingual glyceryl trinitrate tablet (500 mu g) 1 hour after taking 25 mg of sildenafil or placebo. During sildenafil treatment, the subjects were significantly less tolerant of intravenously administered glyceryl trinitrate than during placebo treatment based on the occurrence of a >25 mm Hg decrease in

关键词：氨氯地平/药理学抗高血压药/药理学血压/药物作用交叉研究双盲法用药计划表药物相互作用心率/药物作用高血压/药物疗法高血压/病理生理学硝酸甘油/药理学磷酸二酯酶抑制剂/药理学哌嗪类/药理学参考值血管舒张药/药理学成年人老年人人类男(雄)性中年人

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Decitabine in myelodysplastic syndromes

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SEMINARS IN HEMATOLOGY 2005年第3期42卷 S23-S31页

作者： Saba, HI Wijermans, PW Univ S Florida Coll Med James A Haley Vet Hosp H Lee Moffit Canc Ctr & Res InstDept Internal Me Tampa FL 33612 USA Leyenburg Hosp Dept Haematol The Hague Netherlands

Myelodysplastic syndromes (MDS) are a heterogenous group of hematopoietic stem cell disorders that are multifactorial in their etiology. Aberrant DNA hypermethylation is now thought to be involved in MDS, as numerous tumor-suppressor genes have been identified that are silenced in these patients. Thus, the use of DNA methyltransferase inhibitors, such as 5-aza-2'-deoxycytidine (decitabine, Dacogen, MGI Pharma Inc, Bloomington, MN), for reversal of this process appears to be a rational intervention that may influence the course of the disease. Several phase I/II studies have been conducted using a low-dose schedule of decitabine in MDS patients. Based on these studies, decitabine appears to be effective and generally well tolerated, especially in those patients with worse prognostic indicators. Recent results of a phase III study also confirmed that patients treated with decitabine compared to standard supportive care had higher overall response rates and longer time to AML transformation. Decitabine appears to be a promising new therapy for the treatment of MDS; however, defining the optimal dosing schedule and exploring the possible use in combination with other agents such as the histone deacetylase inhibitors need further evaluation.

关键词： DNA Methylation DNA Modification Methylases/antagonists & inhibitors Drug Administration Schedule drug therapy Prognosis Treatment Outcome *DNA甲基化用药计划表预后 Prognosis Treatment Outcome Histone Deacetylase Inhibitors Myelodysplastic Syndromes decitabine DNA Methylation DNA Methyltransferase Inhibitor Maintenance Therapy Drug Administration Schedule Drug Therapy

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A simple phenolic antioxidant protocatechuic acid enhances tumor promotion and oxidative stress in female ICR mouse skin: dose- and timing-dependent enhancement and involvement of bioactivation by tyrosinase

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CARCINOGENESIS 2000年第10期21卷 1899-1907页

作者： Nakamura, Y Torikai, K Ohto, Y Murakami, A Tanaka, T Ohigashi, H Kyoto Univ Grad Sch Agr Div Appl Life Sci Kyoto 6068502 Japan Kinki Univ Fac Biol Oriented Sci & Technol Dept Biotechnol Sci Wakayama 6496493 Japan Kanazawa Med Univ Dept Pathol 1 Uchinada Ishikawa 9200293 Japan

The modifying effects of topical application of the phenolic antioxidant protocatechuic acid (PA) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse skin tumor promotion were investigated. Dimethylbenz[a]anthracene-initiated female ICR mice were treated with TPA (1.6 nmol) twice weekly for 20 weeks to promote papilloma formation. Pre-treatment with 16 nmol PA 30 min prior to each TPA treatment significantly inhibited the number of papillomas per mouse by 52% (P < 0.05). On the other hand, PA pre-treatment at a high dose (1600 nmol) significantly enhanced tumor numbers by 38% (P < 0.05). Interestingly, in the group treated with a quite high dose (20000 nmol) of PA 5 min prior to each TPA application, the average number of tumors per mouse was reduced by 38%, whereas the same PA dose 3 h before TPA treatment significantly enhanced tumor numbers by 84% (P < 0.01). These results suggested that topically applied PA was converted to compound(s) lacking antioxidative properties and/or rather possessing the potential to enhance tumor development. A similar tendency was also observed in the short-term experiment of TPA-induced inflammation and oxidative stress;i.e. two groups pretreated with PA at 20 000 nmol, 30 min and 3 h before TPA treatment, did not show suppression or even significantly enhanced TPA-induced leukocyte infiltration, H2O2 generation, thiobarbituric acid-reacting substances level and proliferating cell nuclear antigen index, while PA treatment together with TPA significantly suppressed these parameters. Treatment with a high dose (20 000 nmol) of PA alone for 3 h enhanced oxidative stress by reducing glutathione levels in mouse skin, which was counteracted by the tyrosinase inhibitor arbutin, Oxidative stress responses such as leukocyte infiltration and H2O2 generation were also counteracted by arbutin, These results suggested that tyrosinase-dependent oxidative metabolism of PA was at least partially involved in the enhanced effects of PA on TPA-

关键词： 9 10-二甲基-1 2-苯并蒽/拮抗剂和抑制剂 9 10-二甲基-1 2-苯并蒽/毒性抗氧化剂/药代动力学抗氧化剂/药理学抗氧化剂/毒性生物转化致癌物/拮抗剂和抑制剂致癌物/药理学致癌物/毒性皮炎接触性/代谢剂量效应关系药物用药计划表药物协同作用谷胱甘肽/代谢谷胱甘肽过氧化酶/代谢谷胱甘肽转移酶/代谢过氧化氢/代谢小鼠近交ICR 一元酚单氧酶/代谢氧化性应激/药物作用乳头状瘤/化学诱导乳头状瘤/代谢乳头状瘤/预防和控制皮肤/药物作用皮肤/代谢皮肤/病理学皮肤肿瘤/化学诱导皮肤肿瘤/代谢皮肤肿瘤/预防和控制十四酰佛波乙酯/拮抗剂和抑制剂十四酰佛波乙酯/毒性动物女(雌)性小鼠

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