周剂量紫杉醇联合顺铂治疗晚期食管癌临床观察

目的 观察周剂量紫杉醇(PTX)加顺铂(DDP)联合化疗治疗晚期食管癌的近期疗效和毒副反应.方法 晚期食管癌患者48例分为两组,PTX DDP组:PTX 80mg/m2静滴第1,8天;顺铂20mg/d静滴第1～5天.5-Fu DDP CF组:5-Fu 500mg/m2静滴,第1～5天;DDP 20mg/d静滴第1～5天,CF 100mg/次静滴,在5-Fu前2h内给药第1～5天,21天为1周期,2周期后按UICC标准评价近期疗效和毒副反应.结果 PTX DDP方案治疗20例食管癌患者有效率为70%;5-Fu DDP CF方案治疗28例的有效率为50%.前一联合方案总有效率高于后者,有显著性差异(P＜0.05),不良反应也较后者重,但大多数患者能耐受,主要为剂量限制性毒性.表现为Ⅱ～Ⅲ度为主的骨髓抑制.结论 周剂量紫杉醇联合顺铂治疗晚期食管癌近期疗效显著,毒副反应小.     

大剂量醛氢叶酸加氟尿嘧啶持续滴注联合顺铂治疗晚期食管癌临床研究

目的 观察大剂量醛氢叶酸(Leucovorin,LV)加氟尿嘧啶(5-Fluorouracil,5-Fu)持续48 h滴注联合顺铂(Cisplantin,DDP)治疗晚期食管癌与传统DF方案疗效及其不良反应的差别.方法 病理确诊的食管癌60例,随机分成治疗组30例,采用DDP 25 mg/m2静脉滴注30 min,第1～3天;LV 200 mg/m2静脉滴注2h,5-Fu 0.5静脉注射10 min,然后5-Fu 2.5/m2,用输液泵连续输注48 h,每21天重复,2个周期以上评定疗效.对照组30例,采用DDP 25mg/m2静脉滴注30 min,第1～3天;LV 60 mg/m2静脉滴注2h,第1～5天,5-Fu 500 mg/m2静脉滴注8h,每21天重复,2个周期以上评定疗效.结果 近期疗效,治疗组,完全缓解(CR)1例,部分缓解(PR)15例,稳定(SD)9例,进展(PD)5例,总有效率CR+ PR53.3％(16/30).对照组,PR 11例,SD 11例,PD 8例,无PR病例,总有效率36.7％(11/30).恶心、呕吐、口腔粘膜炎、骨髓抑制、腹泻及脱发为主要不良反应.两组均能耐受,未发生Ⅳ度毒性,骨髓抑制对照组比治疗组明显.结论 大剂量LV+ 5-Fu 48 h滴注联合铂治疗晚期食管癌近期疗效较传统DF方案好,不良反应较小,值得进一步扩大研究.     

化学药物联合每周疗法对晚期胃癌的近期效果观察

目的观察紫杉醇(PTX)联合顺铂(DDP)、甲酰四氢叶酸钙(LV)和氟脲嘧啶(5-FU)综合应用每周疗法治疗晚期胃癌的近期疗效和耐受性。方法统计分析2003～2005年24例接受联合化疗的ⅢB～Ⅳ期胃癌患者。结果总有效率58.3%。主要毒副反应为Ⅱ度胃肠道反应、神经毒性和血液系统毒性。结论PTX+DDP+LV+5-FU每周疗法治疗晚期胃癌的近期疗效肯定,毒性可耐受,值得临床推广。     

复方苦参注射液联合放、化疗治疗中晚期食管癌

目的评价复方苦参注射液联合放疗、TP化疗治疗中晚期食管癌的近期临床疗效和药物毒副作用。方法将86例中晚期食管癌患者随机分为对照组和试验组,各43例。对照组给予放疗和TP化疗:放疗总量为60～70Gy(6～7周),同时每周行TP化疗方案(PTX+DDP)。试验组在对照组处理的基础上加用复方苦参注射液20mL+生理盐水200mL静脉滴注,每天1次,3周为1个周期。结果试验组和对照组患者近期疗效比较,差异有显著性(P<0.05),试验组明显高于对照组;两组近期药物的消化道毒性反应、白细胞毒性反应、血小板毒性反应相比较,差异均有显著性(P<0.05),试验组显著低于对照组。结论复方苦参注射液联合放疗、TP化疗可提高中晚期食管癌的近期临床疗效,并减轻放化疗的药物毒副作用,提高患者生存质量。     

紫杉醇 顺铂治疗中晚期食管癌药物疗效观察

目的观察紫杉醇联合顺铂治疗中晚期食管癌的疗效及安全性。方法52例中晚期食管癌患者随机分为两组。治疗组(PTX+DDP):PTX:175mg/m2,静滴3h第一天;DDP75mg/m2,静滴第1天。21天为1周期。对照组(5-Fu+DDP):5-Fu750mg/m2/d,静滴第1～5天;DDP75mg/m2,静滴第1天,21d为1周期。结果治疗组25例食管癌患者的有效率为76%;对照组27例的有效率为48.15%;两组比较有显著性差异(P<0.05)。治疗组白细胞减少发生率高于对照组,但差异无统计学意义,脱发、肌肉关节痛发生率明显高于对照组(P<0.05)。结论紫杉醇联合顺铂治疗中晚期食管癌疗效优于5-Fu+DDP,疗效肯定。不良反应有所增加,但可耐受。     

放疗联合化疗治疗中晚期食管癌的临床分析

目的分析放疗联合化疗治疗中晚期食管癌的临床疗效。方法对符合条件的82例病例,随机分为2组,放疗 化疗(综合组)41例,放疗前用DDP、5-Fu、CF化疗,放疗后再给予4个周期化疗;单纯放疗(单放组)41例。结果综合组和单放组近期疗效CR PR分别为83%和51%(P<0.05),1、2、3年生存率分别为70.7%、51.2%、39.0%和46.3%、29.3%、19.5%(P<0.01),综合组生存率明显高于单放组(P<0.05),但不良反应综合组高于单放组(P<0.05)。结论放疗联合化疗对中晚期食管癌治疗有协同作用,可以提高疗效。     

紫杉醇与顺铂同步联合放疗治疗老年食管癌临床分析

目的评价紫杉醇(PTX)与顺铂(DDP)联合放疗治疗老年食管癌的疗效和毒副反应。方法对60例老年食管癌,进行紫杉醇(PTX)与顺铂(DDP)联合放疗。结果 60例患者均可评价疗效,总有效率31.2%,稳定率51.0%,临床获益率为82.2%。毒副反应主要为剂量限制性毒性,表现为Ⅲ～Ⅳ度骨髓抑制(18.9%)。结论紫杉醇(PTX)与顺铂(DDP)联合放疗治疗老年食管癌有效率较高,毒副反应可耐受。     

小儿肺炎型哮喘46例临床分析

我科2002年2月至2005年8月对62例中晚期食管癌患者进行顺铂（DDP）联合5-氟尿嘧啶（5-Fu）（PF）方案同期放化疗及单纯放疗的疗效对比，报告如下。     

康艾注射液联合放射治疗中晚期食管癌的临床对比研究

目的评价康艾注射液联合放疗治疗中晚期食管癌的近期疗效和放疗不良反应。方法将50例中晚期食管癌患者随机分为对照组和试验组,两组均采用放疗:放疗采用直线加速器6 mV-X线照射,放疗每天2 Gy总量为60⁶6 Gy(666 Gy(6⁷周),试验组在上述放疗基础上再每天静脉注射康艾注射液(长白山制药股份有限公司生产)50 mL,共计30 d,观察两组近期疗效及不良反应。结果试验组的近期总有效率为92.0%,对照组为68.0%,两组差异具有统计学意义(P<0.05)。试验组的Ⅲ/Ⅳ级消化管毒性反应、白细胞毒性反应发生率与对照组比较,均明显减轻(P<0.05)。结论康艾注射液能够有效提高中晚期食管癌放疗的临床疗效,且能显著减少放疗的不良反应。     

中晚期食管癌同步放化疗的护理

早期食管癌症状隐匿,就诊时病变已属中晚期,无法进行根治性手术切除.化疗和放疗均为中晚期食管癌的重要治疗手段[1-2].DDP、5-FU等本身为放射线增敏剂,可增加放疗的局部作用.本科2009年12月～2010年12月对30例中晚期食管癌行PF方案(DDP联合5-FU)化疗同步放射治疗,并采取相应的护理措施,取得较好的效果,现报道如下.     

Cerebral metabolism of [3H]-p-chloroamphetamine

The time-dependent metabolism of intraventricularly administered $\text{[}{}^3\text{H}\text{]-p-}\text{chloroamphetamine}$ was followed. The parent compound and its metabolites were recovered by high pressure liquid chromatography and characterized by high pressure liquid chromatography, thin-layer chromatography, and gas chromatography-mass spectrometry. By 4 hr after injection, two major toluene-soluble metabolites were present in brain. Their biological half-lives were different from the parent compound. On the basis of their analyses, one of the metabolites is p-chloronorephedrine, the other (P₃) is as yet unidentified. Pretreatment with Lilly 110140 prevented or markedly reduced the synthesis of both p-chloronorephedrine and P₃. Iprindole prevented the synthesis of p-chloronorephedrine. The P₃ appeared first in the brain then in the liver, suggesting that both of these organs can metabolize p-chloroamphetamine to this compound. The metabolites were recovered primarily from the nuclear and microsomal fractions following subcellular fractionation of the brain, with small quantities present in the synaptosomal fraction. The level of metabolites was higher in the brainstem than in the neocortex. Glutathione, administered simultaneously with p-chloroamphetamine either intraventricularly or intraperitoneally failed to alter the toxicity of p-chloroamphetamine.     

Clevudine University of Georgia/Abbott/Bukwang/Triangle/Yale University

The pyrimidine analog, clevudine (L-FMAU: 2'-fluoro-5-methyl-beta-L-arabinofuranosyluridine) is a potent antihepatitis B virus (HBV) and anti-Epstein-Barr virus (EBV) agent, discovered by researchers at the University of Georgia, in collaboration with Yale University and Bukwang. Bukwang transferred its technology to Triangle Pharmaceuticals in 1998 together with a license to develop clevudine worldwide except Korea [279649], [281942]. In June 1999, Triangle and Abbott Laboratories entered into a strategic alliance to copromote antiviral products including L-FMAU [326798]. In September 2000, Triangle Pharmaceuticals Inc initiated a 30-day phase I/II evaluation of clevudine in HBV-infected patients [381755]. Clevudine is a much less toxic derivative of the toxic agent P-D-FMAU. The mechanism of action of clevudine is not yet clear, but the agent induces a rapid decrease in HBV nucleic acid as doses increase from 0.3 to 10 mg/kg [319145]. It is believed that the target for clevudine lies in the viral replication mechanism. Clevudine is phosphorylated to the triphosphate form intracellularly. This is removed slowly from the cells, thus exerting a sustained inhibitory antiviral activity [178173], [320720], [320721].     

Spotlight from the American Society for Preventive Cardiology on Key Features of the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guidelines on the Management of Blood Cholesterol

The 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol retains focus on recommendations for statin treatment in the original four statin-eligible groups [those with atherosclerotic cardiovascular disease (ASCVD), diabetes, low-density lipoprotein cholesterol (LDL-C) ≥ 190 mg/dL, and higher risk primary prevention] without the use of treatment initiation or target LDL-C levels from the earlier 2013 American College of Cardiology/American Heart Association (ACC/AHA) guideline, but has several new features. First, patients with primary prevention are divided into those who are at low (< 5%), borderline (5% to < 7.5%), intermediate (7.5% to < 20%), and high (≥ 20%) risk based on the ASCVD risk estimator. Moreover, the new guideline goes further to consider a wider range of factors [now called “risk enhancers”—premature family history of ASCVD, persistently high LDL-C, chronic kidney disease (CKD), metabolic syndrome, conditions specific to women, inflammatory diseases, and high-risk ethnicities] that can be used to better inform the treatment decision. Moreover, more detailed recommendations on how the results of coronary calcium scanning can be used to inform the treatment decision are provided, including how it may be used to “de-risk” certain patients for delaying or avoiding the use of statin therapy. There are also specific sections for cholesterol management in other patient subgroups including women, children, certain ethnic groups, those with CKD, chronic inflammatory disorders and HIV, as well as discussion on the management of hypertriglyceridemia. Importantly, for persons with known ASCVD, a distinction is made for those who are at “very high risk” based on having had two major ASCVD events or one major event and two or more other high risk conditions, such as diabetes or other major risk factors, or bypass surgery or percutaneous intervention. Finally, the concept of a threshold LDL-C for initiating a non-statin therapy (after considering highest tolerated statin dosage) is provided, with ezetimibe recommended as the key non-statin to be added if the LDL-C still remains ≥ 70 mg/dL for all ASCVD patients, and in those who are at “very high risk”, further consideration for using a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. While the new guideline does have greater detail (and arguably, complexity), the refinements provide a strategy for guiding the clinician to target both statin and non-statin therapy to those most likely to derive benefit.     

Pitavastatin Nissan/Kowa Yakuhin/Novartis/Sankyo

Pitavastatin (nisvastatin) is an HMG CoA reductase inhibitor being developed jointly by Nissan, Kowa Kogyo, Novartis and Sankyo for the potential treatment of atherosclerosis and hyperlipidemia.     

N-Nitroso-N-Methyldodecylamine and N-Nitroso-N-Methyltetradecylamine in household dishwashing liquids

Eleven household dishwashing liquids and four household surface cleaners were analysed for N-nitroso-N-methyldodecylamine and N-nitroso-N-methyltetradecylamine by gas chromatography with detection using a Thermal Energy Analyzer. Both nitrosamines were found in three of the dishwashing detergents and one of the surface cleaners. [1-¹⁴C]-N-Nitroso-N-methyldodecylamine was used to determine recoveries, which were between 65 and 88%. Levels of N-nitroso-N-methyldodecylamine ranged from 112 to 661 ppb and those of N-nitroso-N-methyltetradecylamine from 46 to 151 ppb. A simple method was developed to screen the products for N,N-dimethyldodecylamine-N-oxide, a surfactant ingredient suspected of being the source of these nitrosamines. By application of this method it was established that all of the products formulated with this amine oxide contained these two nitrosamines, whereas in products that did not contain this ingredient, these nitrosamines were not detected.     

PROTON AND POTASSIUM TRANSPORT BY H+/K+-ATPases

1. H⁺/K⁺-ATPases are members of the P-type ATPase multigene family. The prototypical H⁺/K⁺-ATPase is the protein that acidifies gastric luminal contents. The physiological and pharmacological significance of this pump has led to a detailed investigation of its biochemistry and molecular and cell biology. 2. Recently, a number of closely related H⁺/K⁺-ATPase isoforms have been discovered. These isoforms are present in organs other than the stomach, including the colon and kidney, where they contribute to acid—base and potassium homeostasis. The structure, expression and physiological roles of the gastric H⁺/K⁺-ATPase and other isoforms are reviewed.     

INTERACTIONS OF Na+, H2O2 AND THE Na+-Ca2+ EXCHANGER STIMULATE Ca2+ RELEASE IN CK1.4 CELLS

1. The present study aimed to demonstrate that interactions of cations, hydrogen peroxide (H₂O₂) and the Na⁺-Ca²⁺exchanger stimulate Ca²⁺ release and oscillations of cytosolic Ca²⁺ [Ca²⁺]i in non-transfected Chinese Hamster Ovary (CHO) C1 cells and in transfected CHO (CK1.4) cells that contained an expression vector coding the Na⁺-Ca²⁺ exchanger sequence. 2. The [⁴⁵Ca²⁺] uptake assay, fura-2 fluorescence imaging and 2² and 2³ factorial orthogonal statistics provide comparative, direct, efficient, quantitative and transient methods to delineate the effects of such interactions on Ca²⁺ influx, Ca²⁺release and [Ca²⁺]i in C1 and CK1.4 cells. 3. In contrast to the control of either Na⁺-, Ca²⁺- or H₂O₂-free or CI cells, an elevated [⁴⁵Ca²⁺] uptake was induced by Ca²⁺, Na⁺ and H₂O₂ individually and in combination, intracellular Ca²⁺ release was activated by H₂O₂ and by combinations of either H₂O₂ and Na⁺, H₂O₂ and the Na⁺-Ca²⁺ exchanger, Na⁺ and the Na⁺-Ca²⁺ exchanger or by H₂O₂, Na⁺ and the Na⁺-Ca²⁺ exchanger and a rise in [Ca²⁺]i was triggered by H₂O₂, Na⁺ and a combination of Na⁺ and the Na⁺-Ca²⁺exchanger. 4. These results indicate that interactions between H₂O₂, Na⁺ and the Na⁺-Ca²⁺ exchanger stimulate intracellular Ca²⁺mobilization via Ca²⁺-induced Ca²⁺ release mechanisms, ATP-activated G-protein coupled P_2y-purinoceptor-sensitive pathways, Na⁺-Ca²⁺ exchanger-mediated Ca²⁺ influx and cation-π interaction (a strong non-covalent force between the cation and the π face of an aromatic structure in the transmembrane protein). 5. The present findings provide important clues for understanding Ca²⁺ signal transduction mechanisms from the plasma membrane to the endoplasmic reticulum.     

Amlodipine/Valsartan/Hydrochlorothiazide

Amlodipine/valsartan/hydrochlorothiazide (HCTZ) is a fixed-dose combination of the well established antihypertensive agents amlodipine (a calcium channel antagonist), valsartan (an angiotensin II receptor antagonist), and HCTZ (a thiazide diuretic). In patients with moderate or severe hypertension, triple combination therapy with amlodipine + valsartan + HCTZ produced significantly greater reductions from baseline in mean sitting systolic and diastolic BP (msSBP and msDBP) than either valsartan + HCTZ, amlodipine + HCTZ, or amlodipine + valsartan in a large, 8-week, randomized, double-blind, multinational, phase III trial. Furthermore, the proportion of patients achieving overall BP control at endpoint was significantly greater with the triple combination regimen than with any of the dual regimens, with significantly more triple combination recipients achieving msSBP and msDBP control at each assessment throughout the trial. Subgroup analyses of this study suggested that amlodipine + valsartan + HCTZ was generally more effective in reducing BP and providing overall BP control than the dual combination therapies, irrespective of age, race, gender, ethnicity, or hypertension severity. Several smaller studies provide data that support the efficacy of amlodipine + valsartan + HCTZ in patients whose BP is inadequately controlled with amlodipine + valsartan, amlodipine + HCTZ, or valsartan + HCTZ dual combination therapy. Treatment with amlodipine + valsartan + HCTZ for up to 8 weeks was generally well tolerated in the large, phase III trial, with most adverse events being transient and of mild to moderate severity.     

EFFECTS OF THE OPIOID PEPTIDES [MET5]ENKEPHALIN-ARG6-PHE7 AND [MET5]ENKEPHALIN-ARG6-GLY7-LEU8 ON CHOLINERGIC NEUROTRANSMISSION IN THE RABBIT ISOLATED ATRIA

1. The effect of the opioid peptides [Met5]enkephalin-Arg6-Phe7 (MEAP) and [Met5]enkephalin-Arg6-Gly7-Leu8 (MEAGL) were compared with those of [Leu5]enkephalin and [D-Ala2,Met5]enkephalinamide (DAME) on cholinergic neurotransmission in the rabbit isolated atria. 2. Rabbit isolated atria had a resting rate of 190 beats/min. In the presence of the beta-adrenoceptor antagonist propranolol (0.3 mumol/l), atria responded to electrical field stimulation with a cholinergically mediated negative chronotropic response. The opioid peptides had no effect on the resting rate, but inhibited the negative chronotropic response to field stimulation. The IC50 values for inhibiting the cholinergic responses were 1.4 mumol/l for [Leu5]enkephalin (LE), 1.4 mumol/l for MEAP, 1.3 mumol/l for MEAGL and 0.2 mumol/l for DAME. Responses of a similar magnitude to exogenous acetylcholine were unaffected. 3. Thus, MEAP, MEAGL and LE had similar potencies but DAME was about seven times more potent in inhibiting cholinergic neurotransmission in the rabbit isolated atria. The site of inhibition appears to be prejunctional.