Effects of Replacement Doses of Sodium-L-Thyroxine on the Peripheral Metabolism of Thyroxine and Triiodothyronine in Man

Studies of the effect of L-thyroxine administration (0.3 mg daily for 7-9 wk) on the peripheral metabolism of (131)I-labeled triiodothyronine (T(3)) and (125)I-labeled thyroxine (T(4)) and on the concentration and binding of T(4) and T(3) in serum were carried out in 11 euthyroid female subjects. Administration of L-thyroxine led to consistent increases in serum T(3) concentration (137 vs. 197 ng/100 ml), T(3) distribution space (39.3 vs. 51.7 liters), T(3) clearance rate (22.9 vs. 30.6 liters/day) and absolute T(3) disposal rate (30 vs. 58 mug/day), but no change in apparent fractional turnover rate (60.3 vs. 60.6%/day). The proportion and absolute concentration of free T(3) also increased during L-thyroxine administration. Increases in serum total T(4) concentration (7.3 vs. 12.8 mug/100 ml) and in both the proportion and absolute concentration of free thyroxine also occurred. In five of the subjects, the kinetics of peripheral T(4) turnover were simultaneously determined and a consistent increase in fractional turnover rate (9.7 vs. 14.2%/day), clearance rate (0.84 vs. 1.37 liters/day), and absolute disposal rate (64.2 vs. 185.0 mug/day) occurred during L-thyroxine administration. Despite these increases in the serum concentration and daily disposal rate of both T(4) and T(3), the patients were not clinically thyrotoxic. However, basal metabolic rate (BMR) values were marginally elevated and, as in frank thyrotoxicosis, T(4)-binding capacities of thyroxine-binding globulin (TBG) and thyroxine-binding prealbumin (TBPA) reduced, suggesting that subclinical thyrotoxicosis was present. Thus, the often recommended replacement dose of 0.3 mg L-thyroxine daily may be greater than that required to achieve the euthyroid state.The studies have also provided additional evidence of the peripheral conversion of T(4) to T(3) in man and have permitted the calculation that approximately one-third of exogenously administered T(4) underwent deiodination to form T(3). To the extent that a similar fractional conversion occurs in the normal state, it can be calculated that a major fraction of the T(3) in serum derives from the peripheral deiodination of T(4) and that only a lesser fraction derives from direct secretion by the thyroid gland.     

Pharmacokinetics of Nikkomycin Z after Single Rising Oral Doses

Nikkomycin Z is an antifungal drug that inhibits chitin synthase. This agent is under development as an orphan product for treatment of coccidioidomycosis. Safety and pharmacokinetics of nikkomycin Z were evaluated in healthy male subjects following single, rising oral doses ranging from 250 mg to 2,000 mg. A total of 12 subjects were recruited and divided into two groups. Group 1 (n = 6) received two out of three doses of 250 mg, 1,000 mg, or 1,750 mg and a placebo randomly in place of one of the doses. Group 2 (n = 6) received two out of three doses of 500 mg, 1,500 mg, or 2,000 mg and a placebo in place of one of the doses. Subjects were confined to the study unit overnight prior to dosing, and 12 blood samples were collected over 24 h postdosing while subjects were confined. Subjects returned for additional blood samples and safety evaluations at 48 h and 72 h after each dose. There was a 2-week washout period between doses. Plasma drug concentrations were determined using a validated high-performance liquid chromatography method. Nikkomycin Z was absorbed after oral administration, reaching a maximum concentration in serum of 2.21 μg/ml at 2 h postdose and an area under the concentration-time curve from 0 h to infinity of 11.3 μg·h/ml for the 250-mg dose. Pharmacokinetics appeared linear over the range of 250 to 500 mg; however, relative bioavailability was about 62 to 70% for the 1,000-mg dose and 42 to 47% for doses between 1,500 and 2,000 mg. The mean terminal half-life ranged from 2.1 to 2.5 h and was independent of dose. No serious or dose-related adverse events were observed. This study provides a basis for pharmacokinetic simulations and continued studies of nikkomycin Z administered in multiple doses.Nikkomycin Z (NikZ) is an antifungal agent derived from Streptomyces tendae. This agent has activity against endemic fungi, particularly Coccidioides spp. NikZ inhibits chitin synthases, which catalyze the synthesis of chitin, an essential structural component of the fungal cell wall (9, 11). This agent has been demonstrated to have activity in mouse models of coccidioidomycosis, histoplasmosis, and blastomycosis after oral gavage administration (2, 5-7). Compared to conventional antifungal agents, including fluconazole and amphotericin B, NikZ resulted in greater killing of Coccidioides spp. and was able to sterilize lung lesions in seven of eight mice dosed with 50 mg/kg/day for 6 days. The conventional agents tested did not sterilize lung lesions in any case (7).In a variety of preclinical toxicology studies involving rats and dogs, NikZ was well-tolerated with no consistent organ toxicities. The no observed effect level was at least 300 mg/kg of body weight, based on single and chronic dosing studies. In some of these studies the maximum dose of 1,000 mg/kg was given without any detectable toxicity (data on file at the University of Arizona). NikZ is expected to provide selective toxicity against susceptible fungi, since chitin synthases are not present in mammals.This study represents the first administration of NikZ to humans. NikZ was studied at doses ranging from 250 to 2,000 mg as a single dose given orally in fasting healthy volunteers. The primary goal was to determine the safety, tolerance, and pharmacokinetics.(Preliminary results for this study were presented at the 37th Interscience Conference on Antimicrobial Agents and Chemotherapy, Toronto, ON, Canada, 28 September to 1 October 1997.)     

不同剂量的替米沙坦对阵发性心房颤动的影响

目的：观察不同剂量的替米沙坦对阵发性心房颤动的预防效果,并探讨其量效关系和主要作用机制。方法：将符合入选条件的123例高血压病合并心功能不全或左室肥厚或冠心病患者随机分为替米沙坦20mg组（n=30）、40mg组（n=30）、80mg组（n=31）和对照组（n=32）。各组均口服相同剂量和时间的胺碘酮,对照组避免应用血管紧张素转换酶抑制剂（ACEI）和血管紧张素受体拮抗剂（ARB）。随访6个月,分别观察房颤复发例数、房颤发作次数、房颤首次复发时间及左室、左房内径的变化。结果：替米沙坦80mg组房颤首次复发的时间较对照组显著延长（P〈0.05）,房颤复发例数与次数6个月内显著减少（P〈0.05）,左室舒张末内径（LVEDD）与左房内径（LAD）在3个月内与对照组比较无显著差异（P〉0.05）,6个月内显著缩短（P〈0.05）。20mg组、40mg组与对照组比较差异均无统计学意义（P〉0.05）。结论：不同剂量的替米沙坦对预防房颤复发的效果不同,存在着量效关系,其作用机制主要与抑制心室、心房重构的强弱有关。     

Pharmacokinetics of EDP-420 after Ascending Single Oral Doses in Healthy Adult Volunteers

EDP-420 (EP-013420, S-013420) is a first-in-class bicyclolide (bridged bicyclic macrolide) currently in clinical development for the treatment of respiratory tract infections. It has good preclinical pharmacokinetic properties across multiple species and potent in vitro and in vivo activity against respiratory tract infection pathogens, including Haemophilus influenzae, atypical organisms (e.g., Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila), and multidrug-resistant streptococci. The safety, tolerability, and pharmacokinetics of an orally administered EDP-420 suspension in 40 healthy adult subjects were assessed in a randomized, double-blind, placebo-controlled, ascending single-dose study. Eligible subjects were sequentially randomized into one of five study groups (i.e., 100-, 200-, 400-, 800-, or 1,200-mg dosing groups) consisting of eight subjects (six active and two placebo) each. EDP-420 was well tolerated. There were no serious adverse events reported, nor were there any dose-limiting clinical or laboratory adverse events reported. EDP-420 was rapidly absorbed after a single oral dose. The mean plasma terminal half-life ranged from 15.6 to 20.1 h with low clearance. At the 400-mg dose, the area under the curve was 14.4 μg·h/ml, which well exceeded the required area under the concentration-time curve to cover common respiratory tract infection pathogens based on preclinical pharmacokinetic/pharmacodynamic modeling. The long half-life and high systemic exposure of EDP-420 support once-daily dosing and may allow for shorter treatment durations compared to other macrolide antibiotics. Based on its human pharmacokinetic profiles, taken together with its in vitro/in vivo activity against common respiratory pathogens, EDP-420 warrants efficacy trials for the treatment of respiratory tract infections.Macrolide antibiotics have been used effectively and safely as first-line treatments for respiratory tract infections (RTI) for more than 50 years (34). However, the incidence of worldwide resistance to antibiotics (including macrolide antibiotics) is increasing. For example, Streptococcus pneumoniae is the most commonly implicated bacterium in RTI, being responsible for 45% of the cases of community-acquired pneumonia and 34% of acute sinusitis (1, 2). Fully 31% of S. pneumoniae infections in the United States have yielded organisms resistant to the macrolide antibiotic erythromycin, and nearly one-third are resistant to penicillin. S. pneumoniae resistance is more common in Asia, where 80% of S. pneumoniae infections are erythromycin resistant, and 53% are penicillin resistant (11, 35, 38). Thus, there is an urgent need to develop new antibiotics with activity against a broad spectrum of pathogens (especially resistant strains) commonly encountered in community-acquired RTI (1, 11, 35, 38).EDP-420 (formerly EP-013420 and S-013420) is a novel bridged bicyclic macrolide antibiotic (the structure is shown in Fig. ​Fig.1)1) currently in clinical development for the treatment of RTI. It was designed specifically to combat atypical and respiratory tract pathogens that have acquired resistance to macrolide antibiotics. EDP-420 has a unique 6,11-O-bridging moiety, with replacement of the cladinose sugar by a 3-keto group (33). RNA footprinting suggests that EDP-420 binds near the entrance to the peptide exit tunnel of the 50S ribosomal subunit from E. coli and forms interactions with both domain V and domain II of 23S rRNA (36). The additional binding motif to the 50S ribosomal subunit (i.e., a second binding site along the 23S rRNA hairpin loop 35 of domain II) provided by the 6,11-O-bridging moiety should help overcome macrolide, lincosamide, and streptogramin B resistance, resulting in an improved structure-activity relationship.Open in a separate windowFIG. 1.Structure of EDP-420.EDP-420 exhibits potent in vitro activities against RTI pathogens, including multidrug-resistant streptococci and atypical organisms (e.g., Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila) (21, 28, 31). For example, MIC₉₀ (i.e., the MIC required to inhibit the growth of 90% of organisms) for EDP-420 against 115 strains and 100 clinical isolates of S. pneumoniae, including macrolide-resistant strains carrying mefA and/or ermB genes, was 0.25 μg/ml, which is comparable to that of telithromycin (MIC₉₀ = 0.125 μg/ml) and significantly better than that of clarithromycin, azithromycin, and erythromycin (MIC₉₀ > 64 μg/ml) (37). The antibacterial activity of EDP-420 against S. pyogenes carrying constitutive type ermB was 32 times more potent than that of telithromycin (27). EDP-420 is potent against methicillin-susceptible Staphylococcus aureus, including strains with inducible type ermA/C (27). The MIC₉₀ of EDP-420 against Legionella spp. was 0.031 μg/ml, which is comparable to that of levofloxacin and significantly more active than erythromycin and azithromycin (9, 24). In one study, 80% of S. pneumoniae strains (10 strains, including an erythromycin-resistant strain) and all of the Haemophilus influenzae strains (10 strains) tested showed minimum bactericidal concentration/MIC ratios of <4, and EDP-420 killed more than 99.9% of viable cells of S. pneumoniae and of H. influenzae at 2× the MIC within 4 h (21). The postantibiotic effects of EDP-420 on two strains of H. influenzae, SR24159 and SR1280, lasted 4.3 and 2.2 h, which exceed and were comparable to the corresponding values for clarithromycin (2.0 and 0.2 h) and telithromycin (4.3 and 2.3 h), respectively (21). The growth of H. influenzae in the infected epithelial layers was still inhibited 12 h after the removal of EDP-420; however, bacterial growth resumed almost immediately after the removal of clarithromycin, telithromycin, and levofloxacin (26). EDP-420 showed potent intracellular activity and persistent effects against L. pneumophila both in the alveolar epithelial cells and in the bone marrow macrophages (25).In vivo, EDP-420 also demonstrated efficacy against S. pneumoniae, S. pyogenes, S. aureus, and Mycobacterium avium in mouse protection tests; against S. pneumoniae and H. influenzae in a rat lung infection model; and against penicillin- and quinolone-resistant pneumococci in a rabbit meningitis model (3-6, 17, 19, 20, 22, 28, 30, 31). The oral mean effective doses of EDP-420 sufficient to protect 50% of the mice (ED₅₀) from lethal infection were 2.93, 3.27, 3.12, and 2.12 mg/kg against S. pneumoniae SR16605, S. pneumoniae SR20946 (ermB), S. pneumoniae SR26113 (ermB), and S. pyogenes C-203, respectively, while telithromycin required higher doses of 3.07, 16.5, 3.65, and 4.24, respectively (31). The in vivo efficacy of EDP-420 against rat lung infection caused by H. influenzae SR11925 and SR1280 was comparable to that of telithromycin (31). EDP-420 nonclinical pharmacokinetics (PK) across multiple species displayed a long half-life, as well as extensive distribution and uptake into respiratory tissue and fluids (12-15, 28, 30). The preclinical safety results and good PK properties, along with the in vivo antimicrobial profiles and results of the efficacy studies in animals, supported the decision to begin phase 1 testing in healthy adult volunteers.(This study was presented in part at the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, in September 2007.)     

The Response of Thyrotropin and Triiodothyronine to Various Doses of Thyrotropin Releasing Hormone in Normal Man

Abstract. The relationship between serum thyrotropin (TSH) and serum triiodothyronine (T3) before and after injection of different doses of thyrotropin releasing hormone (TRH), given as single injections or as multiple injections with short intervals, was investigated in normal men. A positive correlation between prestimulated serum TSH and serum T₃ levels and between the increase in the serum TSH and the serum T3 levels after TRH was found when repeated tests were performed in the same individual. There was a dose dependent TSH and T3 response to TRH. The smallest dose that produced a maximal response of both TSH and T3 was only 30 ug TRH. After six injections of 30 ug TRH with an interval of 30 minutes the increase in TSH was two times and the increase in T3 was three times as high as the maximal increase after single injections of TRH. This test with multiple injections of TRH may prove to be of clinical value in the measurement of both pituitary and thyroid function in selected patients. The close positive correlation between the serum TSH and serum T3 levels in basal conditions, demonstrated in four normal subjects in this study, probably reflects the steady state level determined by the hypothalamus from which the feedback control of TSH secretion operates.     

The Response of Thyrotropin and Triiodothyronine to Various Doses of Thyrotropin Releasing Hormone in Normal Man

Abstract. The relationship between serum thyrotropin (TSH) and serum triiodothyronine (T₃) before and after injection of different doses of thyrotropin releasing hormone (TRH), given as single injections or as multiple injections with short intervals, was investigated in normal men. A positive correlation between prestimulated serum TSH and serum T₃ levels and between the increase in the serum TSH and the serum T₃ levels after TRH was found when repeated tests were performed in the same individual. There was a dose dependent TSH and T₃ response to TRH. The smallest dose that produced a maximal response of both TSH and T₃ was only 30 μg TRH. After six injections of 30 μg TRH with an interval of 30 minutes the increase in TSH was two times and the increase in T₃ was three times as high as the maximal increase after single injections of TRH. This test with multiple injections of TRH may prove to be of clinical value in the measurement of both pituitary and thyroid function in selected patients. The close positive correlation between the serum TSH and serum T₃ levels in basal conditions, demonstrated in four normal subjects in this study, probably reflects the steady state level determined by the hypothalamus from which the feedback control of TSH secretion operates.     

Effects of Different Doses of Chlorpromazine on Renal Function in the Dog

This study was carried out to examine the effects of low ‘alpha-blocking’ and higher ‘membrane-stabilizing’ doses of chlorpromazine (CPZ) on renal function. CPZ was given at slow infusion rate either intravenously or into the left renal artery at three levels (0.5–1.0, 3–8, and 10–15 mg/kg) to 10 anesthetized dogs. An increase in plasma hemoglobin sometimes occurred within few minutes after infusion of more than 10 mg/kg CPZ, probably due to a hemolytic effect of such high doses. Systemic infusion of 0.5–1 mg/kg CPZ caused an increase in urine volume, sodium excretion, and renal plasma flow, and a decrease in filtration fraction and free water clearance was demonstrated in all dogs. At higher CPZ doses renal plasma flow increased further, whereas urine volume and electrolyte excretion were of the same order at all dose levels. A 21 % decrease in tubular maximum para-aminohippurate transport (TmpAH) was observed at the highest CPZ doses. After unilateral renal intra-arterial CPZ infusion the percentage change in urine volume, urinary sodium excretion, and TmPAH were of the same order on the infused side as on the contralateral side. Even though the results at all dose levels can be explained by an ‘alpha-blocking’ effect of CPZ, possible membrane-stabilizing effects of CPZ cannot be excluded.     

不同剂量右美托咪啶对拔管期心血管反应的影响

目的：观察手术结束前单次静脉输注不同剂量右美托咪啶对全麻苏醒拔管期患者心血管反应的影响,探讨右美托咪啶在拔管期应用的最佳剂量。方法：美国麻醉师协会（AmericanSocietyofAnesthesiologists,AsA）评分I或Ⅱ级择期行腹腔镜胆囊切除术的患者80例,将其随机均分为A、B、C、D4组,每组20例。手术结束前10min各组分别静脉输注如下药物：A组0,9％氯化钠液10mL,B组右美托咪啶0．3μg／kg,C组右关托咪啶0．5μg／kg,D组右美托咪啶0．7μg／kg。记录手术前、拔管前1min、拔管时、拔管后1min、5min、10min、20min、30min的平均动脉压（MAP）和心率（HR）;观察患者呼吸恢复时间、苏醒时间、拔管时间及围拔管期不良反应发生情况。结果：与手术前比较,拔管前1min、拔管时、拔管后1minA组的MAP、HR及B组的MAP均显著升高（P〈0．05）,而C、D两组MAP、HR变化不明显。拔管后5min、10min、20min、30min时C、D组MAP和HR与手术前比较显著降低（P〉0．05）。D组有4例发生低血压和5例发生心动过缓,显著高于其余3组;D组患者自主呼吸恢复时间、拔管时间及苏醒时间与A、B、C3组比较,显著延长（P〉0．05）;拔管期间C、D组的呛咳和躁动发生率显著低于A、B两组（P〉0．05）。结论：0．5μg／kg右美托咪啶可以有效抑制全麻苏醒拔管期的心血管反应并减轻拔管期躁动、喻咳等不良反应窟生．同时不影响今廉拔管及苏醒时间．     

不同剂量二甲双胍对抗精神病药物所致肥胖的疗效

目的探讨二甲双胍治疗抗精神病药物导致的体质量增加的疗效与剂量关系。方法将长期服抗精神病药物治疗(≥1年)伴肥胖的246例患者,按随机数字表法分为研究A组61例、研究B组62例、研究C组61例、对照组62例。研究A组、研究B组、研究C组分别给予二甲双胍750 mg·d-1、1 000 mg·d-1、1 500 mg·d-1治疗6个月,对照组不予干预直接随访;分别于入组前及入组后1、2、3、6个月测定身高、体质量、空腹血糖。结果各研究组体质量和BMI变化与对照组比较:研究A组在入组后1、2、3、6个月时差异均无统计学意义(均P>0.05);研究B组在入组后1、2个月时差异无统计学意义(均P>0.05),在3、6个月时差异有统计学意义(体质量明显下降,均P<0.05);研究C组在入组后1个月时差异无统计学意义(P>0.05),在2、3、6个月时差异有统计学意义(体质量明显下降,P<0.05或P<0.01)。各研究组空腹血糖减分值在各时间点差异均无统计学意义(均P>0.05);而在入组后6个月各研究组空腹血糖稳定或略降,对照组则呈升高趋势,各研究组血糖减分值分别与对照组比较,差异均有统计学意义(均P<0.01)。结论二甲双胍能有效降低长期抗精神病药物治疗伴肥胖患者的体质量,其剂量在1 000~1 500 mg·d-1效果更明显。     

Repeated Doses of Combined Oral Lysine Acetylsalicylate and Metoclopramide in the Acute Treatment of Migraine

The combination of lysine acetylsalicylate and metoclopramide is effective in the treatment of migraine attacks. It was unknown whether repeated doses could improve efficacy.
The aim of this open trial was to evaluate the effects of a second, and eventually a third dose of lysine acetylsalicylate and metoclopramide when a first dose of the treatment was ineffective. Patients were asked to take a second dose 2 hours after a first dose when they thought that the first dose was ineffective. They were allowed to take a third dose or their rescue medication 2 hours after the second dose when they judged that the treatment remained ineffective.
Two hundred ninety-two patients were included in the study; 262 of the 292 patients treated 517 attacks.
Headache relief (reduction in headache severity from grade 3 or 2 to grade 1 or 0) was observed in 54.8% of attacks after one dose, in 48.1% of attacks after a second dose, and in 40.3% of attacks after a third dose.
Complete headache relief without recurrence and without use of a rescue medication was reported in 37% of the total attacks.
The patients judged their treatment as good or excellent in 78% of attacks treated with one dose, in 41% of those treated with two doses, and in 19% of those treated with three doses.
Tolerance, as judged by the patients, was considered good in 92% of treated attacks. Minor side effects occurred in 6% of attacks after a first dose, in 4.5% of attacks after a second dose, in 1.5% of attacks after a third dose, in 2% after unspecified delay, and in 14% overall.
In conclusion, the efficacy of lysine acetylsalicylate and metoclopramide in the treatment of migraine attacks can be improved by repeated doses. It is well tolerated.     

不同剂量纳洛酮对术后舒芬太尼镇痛的影响

目的:观察不同剂量纳洛酮对术后采用患者静脉自控镇痛(patient-controlled intravenous analgesia,PCIA)方式给予舒芬太尼的镇痛效果的影响及对患者术后恶心呕吐的影响。方法:选择美国麻醉医师协会(American Society of Anesthesiologists,ASA)分级Ⅰ~Ⅱ级、在全身麻醉联合硬膜外麻醉下行全子宫或者全子宫加双附件切除术的患者100例,按照随机数字表将患者随机分为C组、N1组、N2组、N3组,每组25例。C组硬膜外注射0.9%氯化钠液4 mL,N1、N2、N3组分别硬膜外注射5、10、20μg/mL的纳络酮4 mL,静脉注射舒芬太尼0.1μg/kg作为负荷剂量的镇痛药物后应用舒芬太尼静脉镇痛泵(4mL/h)。手术后6、12、24 h观察患者的视觉模拟评分(visual analogue scale,VAS)及恶心呕吐评分等不良反应。结果:(1)与C组比较,N1组术后6、12 h内静息和活动时的VAS评分均较低(P0.05),N3组术后6 h内静息和活动时的VAS评分较高(P0.05)。N2组与C组比较差异无统计学意义(P0.05)。N2组、N3组术后6、12 h内静息和活动时的VAS评分明显高于N1组(P0.05/0.01);(2)与C组比较,N1组、N2组、N3组恶心或呕吐发生率较低(P0.05),恶心或呕吐的评分较低(P0.05/0.01)。与C组比较,N1组、N2组、N3组观察期间需要应用昂丹斯琼的患者例数较少(P0.05)。4组患者均无其他不良事件发生。结论:硬膜外应用小剂量纳络酮可以有效地减少术后舒芬太尼PCIA所引起的恶心呕吐,5μg/mL的纳络酮同时还可增强舒芬太尼的镇痛效能。     

Effects of Different Doses of Acetylsalicylic Acid on Renal Function in the Dog

This study was carried out in order to examine the effect of increasing doses of intravenously administered lysine-acetylsalicylic acid (ASA) on renal function in dogs. The first purpose was to examine the acute effects on renal water and solute output. The second purpose was to correlate the para-aminohippuric (PAH) clearance measurements with measurement of renal PAH extraction and renal blood flow (RBF). After 7 mg/kg ASA (20–80 μg SA/ml plasma) a decrease in sodium excretion was observed in all dogs. With increasing ASA doses, the urine sodium excretion declined to 23 % of the control period excretion. Tubular reabsorption of free water increased 10%. A significant and dose-related decrease in PAH clearance was observed in all dogs, from 108.7 ml/min after 7 mg/kg ASA to 58.8 ml/min after 200 mg/kg ASA. The creatinine clearance was unchanged. PAH extraction fell in all dogs. RBF (measured by flowmeter) decreased 21 % at the highest plasma SA levels, as compared with 46 % decrease in PAH clearance. ASA seems to inhibit tubular transport of PAH. Inhibition of prostaglandin synthesis by ASA offers one explanation of the effects on RBF and sodium excretion.     

不同剂量右美托咪啶复合罗哌卡因对臂丛神经阻滞效果的影响

目的探讨不同剂量右美托咪啶复合罗哌卡因对臂丛神经阻滞效果的影响。方法选取2014年4月~2016年3月我院收治的83例上肢手术患者。随机分为对照组41例和观察组42例。对照组注射右美托咪啶50μg+罗哌卡因40ml实施麻醉,观察组注射右美托咪啶100μg+罗哌卡因40ml麻醉,观察对比两组运动阻滞起效、持续时间,感觉阻滞起效、持续时间,术后镇痛时间、疼痛评分及不良反应发生率。结果观察组运动及感觉阻滞起效时间均低于对照组,运动及感觉阻滞持续时间均高于对照组,差异具有统计学意义(P0.05);观察组术后镇痛时间长于对照组,术后疼痛评分低于对照组,差异具有统计学意义(P0.05);两组不良反应发生率对比,差异无统计学意义(P0.05)。结论大剂量右美托咪啶复合罗哌卡因对臂丛神经阻滞效果较佳,运动及感觉阻滞起效时间短,阻滞持续时间长,术后镇痛时间长,可减轻患者疼痛程度,安全性高。     

不同剂量DMPA对哺乳期妇女卵巢功能恢复的影响

[目的]比较不同剂量醋酸甲羟孕酮（DMPA）应用于哺乳期妇女后卵巢功能的恢复情况,以选择最佳避孕剂量.[方法]选择应用DMPA避孕满1年的哺乳期妇女,共83例,按注射剂量分为两组：Ⅰ组43例,注射剂量150 mg;Ⅱ组40例,注射剂量75 mg.应用基础体温测量法和超声监测比较两组对象停用DMPA后基础体温、卵泡发育及排卵情况.[结果]停用第1月复诊,两组基础体温、排卵情况均无显著差异（P〉0.05）;第2及第3月复诊基础体温、排卵率均有显著差异（P〈0.05）,低剂量组均明显优于高剂量组.[结论]在中国哺乳期妇女中应用低剂量DMPA作为避孕措施,停针后基础体温可较快恢复呈双相,排卵也较快恢复,即卵巢功能可较快恢复正常,其高效、经济,患者易于接受,值得推广使用.     

不同剂量利多卡因预处理对罗库溴铵注射痛的影响

目的比较利多卡因不同剂量预处理对罗库溴铵注射痛的影响。方法 120例行全身麻醉择期手术的患者按照完全随机的方法分为利多卡因10mg3mL预处理组（A组）,利多卡因25mg3mL预处理组（B组）,利多卡因50mg3mL预处理组（C组）,生理盐水3mL预处理组（D组）。观察不同剂量的利多卡因预处理对罗库溴铵注射痛的影响。结果 A、B、C和D组注射罗库溴铵的疼痛发生率分别为53%、27%、3%和90%。与生理盐水预处理组相比,利多卡因预处理组能明显减轻罗库溴铵引起的注射痛（P〈0.01）;剂量越大,效果越明显。结论利多卡因10、25、50mg预处理均能显著降低罗库溴铵注射时引起的疼痛,以50mg利多卡因更为有效。     

术前预注不同剂量地塞米松对腹腔镜胆囊切除术患者术后恢复的影响

【目的】观察术前给予不同剂量的地塞米松对腹腔镜胆囊切除术（LC）患者术后恢复的影响。【方法】分析本院219例LC临床资料,术前分别予地塞米松8mg（A组）69例、地塞米松4rag（B组）71例、等剂量生理盐水（C组）79例。术后第1h、4h、6h、12h进行VAs镇痛评分,并记录术后不良反应。【结果】A、B组VAS镇痛评分均较C组显著降低（P〈0．05）;A组与B组相比,术后VAs评分差异无统计学意义（P〉0．05）。术后恶心、呕吐发生率A组明显低于B、C组（P〈0．05）。术后所需止痛药,A、B、C组差异无统计学意义（P〉0．05）。【结论】术前常规应用8mg地塞米松可减少LC患者术后疼痛,同时减少术后恶心呕吐发生率。     

不同剂量的右美托咪定复合舒芬太尼在子宫全切术中的镇痛效果研究

【目的】探讨不同剂量的右美托咪定复合舒芬太尼在子宫全切术中的镇痛效果。【方法】选取行择期开腹子宫全切术的患者80例,随机分成四组,每组20例。A组（对照组）用舒芬太尼镇痛,B组（低剂量组）用低剂量右美托咪定复合舒芬太尼镇痛,C组（中剂量组）用中剂量右美托咪定复合舒芬太尼镇痛,D组（高剂量组）用高剂量右美托咪定复合舒芬太尼镇痛,通过观察并记录四组不同时点的平均动脉压（MAP）、心率（HR）、脉搏血氧饱和度（SpO2）和呼吸频率（RR）,同时记录四组患者不良反应的情况,比较四组的临床镇痛效果。【结果】右美托咪定复合舒芬太尼比单独使用舒芬太尼有更好的镇痛、镇静效果;中剂量组镇痛效果比低剂量组确切、不良反应比高剂量组少。【结论】中剂量的右美托咪定复合舒芬太尼在子宫全切术中有更好的镇痛效果,值得临床推广。