胆道感染时合理选用头孢类抗生素的实验研究

目的：测定头孢哌酮等七种常用抗生素在胆汁中的药代动力学参数、以便为临床医生治疗胆道感染时提供合理选择抗菌药物的理论依据。方法：犬为实验动物、分别静脉注射头孢哌酮(先锋必),头孢三嗪(罗氏分)．头孢他定(复达欣)．头孢唑啉(先锋Ⅴ),头孢拉定(先锋Ⅵ),头孢呋新(西力欣)、头孢美唑(先锋美他醇)等抗生素后．用微生物法测定胆汁中的药物浓度．经3P87软件进行数据处理．分别得出各抗生素在胆汁中的峰值浓度(Cmax)、峰值时间(Tpeak)、半衰期(T1／2/β)、清除率(CL)、表观分布容积(Va)。结果：先锋必的Cmax最高(2464.5μg／ml),罗氏芬的Cmax稍低于先锋必、但T1／2β最长(3024min)．先锋Ⅴ、复达欣．先锋Ⅵ的Cmax,T1／2β低于前二．但明显高于西力欣,先锋美他醇。结论：胆道感染时,本组七种抗生素中罗氏芬、先锋必为首选药;先锋Ⅴ、先锋Ⅵ虽不及前二．它们具有经济．药源广的优点．仍可广泛用于治疗胆道感染的抗生素。     

纳洛酮在使用头孢类抗生素期间饮酒致双硫醒反应中的应用

纳洛酮（Naloxone），又名烯丙羟吗啡酮，为阿片受体阻断剂，自1960年首次成功合成以来，由于其对正常人无药理作用，安全性大，疗效显著，因此在临床上应用范围越来越广泛。本文统计了我院急诊科收治的使用头孢类抗生素期间饮酒导致双硫醒反应的60例病人，并探讨纳洛酮在其中的应用。     

阿奇霉素联合头孢类抗生素治疗社区获得性下呼吸道感染的疗效观察

目的 探讨阿奇霉素联合头孢类抗生素治疗下呼吸道感染的临床疗效。方法 随机选择下呼吸道感染164例分为三组：阿奇霉素联合头孢类组（A组）60例，单独阿奇霉素组（B组）46例，单独头孢类抗生素组（C组）58例，比较3组患者治疗后的临床疗效及不良反应。阿奇霉素0．5g，每131次静滴，连续7～10天；头孢噻肟钠2g，每132次静滴，连续7～10天。结果 A组显效率、总有效率均高于其他两组，差异有显著统计学意义（P〈0．01）。结论 阿奇霉素联合头孢类抗生素对治疗下呼吸道感染较单独应用阿奇霉素或头孢类抗生素有良好的疗效，不良反应发生率与单独用阿奇霉素相比差异无统计学意义（P〉0．05）。     

白细胞减少症皮窗细胞反应的临床研究

目的 :分析研究白细胞减少症患者皮窗细胞反应的变化与机体抗感染防御能力的关系。方法 :对未经治疗的原发性白细胞减少症患者 3 8例及正常对照者 3 0例进行皮窗实验 ,并比较患者中白细胞被激发者与不被激发者之间以及白细胞减少症治疗前后皮窗细胞反应的变化。结果 :3 8例患者中 ,2 3例 ( 60 .5 % )患者皮窗反应结果均相似 ,15例 ( 3 9.5 % )患者皮窗细胞反应弱于正常对照组 (P <0 .0 1) ;白细胞被激发者与不被激发者之间皮窗细胞反应差异无显著性意义 ;15例皮窗细胞反应弱的白细胞减少症患者治疗前后的皮窗细胞变化中 ,9例改变明显 ,6例无明显改变。结论 :白细胞减少症皮窗渗出物细胞变化可直接反应机体抗感染防御能力 ,初步认定白细胞减少症患者机体防御能力不一定均会下降     

抗甲状腺药物不良反应的再认识

抗甲状腺药物(ATD)是治疗甲状腺功能亢进症主要手段,其不良反应备受学者们关注.ATD常用药物为丙基硫氧嘧啶(PTU)和甲巯咪唑(MMI).总的来说,ATD治疗是安全且有效的,但其临床不良反应亦较常见,如对肝脏、血液系统的毒性作用、抗中性粒细胞胞浆抗体相关性肺小血管炎、低血糖、变态反应、肌肉损伤等,一般程度较轻,如能及时停用ATD则能够自行恢复,但亦可出现少见、严重的副作用,可能存在潜在致命的危险,故需引起临床医生的重视.MMI与PTU比较,其不良反应显著低于PTU,且前者大多具有剂量依赖性,后者与药物的剂量无显著相关.此外,PTU的肝毒性强于MMI,甚至可能发生致命性肝损伤和肝衰竭,在儿童甲亢治疗中推荐首选MMI.

Abstract：

Antithyroid drugs(ATD)is the main treatment for hyperthyroidism and its adverse reactions have been much concerned by physicians. Methimazole(MMI)and propylthiouracil(PTU)are the two common antitithyroid drugs used currently. Generally, the ATD are safe and effective, though their clinical adverse reactions are also relatively common. The toxic effects include liver damage and leukocytopenia, antineutrophil cytoplasmic antibody-associated pulmonary small-vessel vasculitis, hypoglycemia, allergic reactions, muscle impairment,and so on. They are usually reversible and disappear spontaneously when the drug is discontinued. However,the serious rare side effects can also occur and there may have potentially deadly threatening effects which need to be cautious for the clinicians. MMI is usually preferred over PTU because it has significantly fewer side effects. And unlike the dose-dependent side effects of MMI, there has no significant correlation between adverse reaction and drug dosage in using PTU. Moreover, PTU has more severe hepatotoxity than MMI, even fatal liver impairment and liver failure. The risk of liver damage from PTU is an important concern, particularly in children. For this reason, MMI is the first choice for treating children with hyperthyroidism.     

慢性肝病合并自身免疫性血液系统疾病的临床特征及应用糖皮质激素治疗效果分析

目的分析慢性肝病合并免疫性血液系统疾病的临床特征,探究糖皮质激素的疗效。方法回顾性分析2008年1月—2019年12月北京地坛医院收治的17例慢性肝病合并免疫性血液病患者的临床资料,根据血液病种类分为3组:自身免疫性溶血性贫血(AIHA)组、免疫性血小板减少症(ITP)组、Evans综合征组。进行糖皮质激素治疗及肝病相关治疗后,比较3组治疗前后临床资料及实验室检查指标。计量资料两组间比较采用Mann-Whitney U检验。结果 17例慢性肝病患者中有15例非病毒性肝炎患者,其中自身免疫性肝病9例(占52.9%)。17例患者血液系统疾病分布:AIHA患者6例,ITP患者8例,Evans综合征患者3例。其中13例患者进行糖皮质激素治疗,达到完全缓解或部分缓解者共12例,总有效率92.3%。ITP组TBil、DBil治疗后较治疗前显著下降[35.8(14.3～58.0)μmol/L vs 165.6(21.3～374.3)μmol/L,Z=-2.205,P=0.027;24.9(7.0～43.3)μmol/L vs 121.9(11.7～279.9)μmol/L,Z=-2.205,P=0.027];AIHA组血红蛋白治疗后较治疗前显著上升[94.0(65.0～993)g/L vs 62.2(42.3～80.5)g/L,Z=-2.242,P=0.025]。结论多种类型慢性肝病均可合并免疫性血液系统疾病,其中自身免疫性肝病合并免疫性血液系统疾病的发病率较高;糖皮质激素是慢性肝病合并免疫性血液系统疾病安全有效的治疗方法。     

全身炎症反应综合征患者凝血系统功能紊乱的研究

目的　研究全身炎症反应综合征 (SIRS)时凝血系统的变化及其对SIRS预后的影响。方法　按照SIRS诊断标准将入住急诊监护病房的患者分为SIRS组 10 0例、非SIRS组 5 0例 ,另选健康正常人 5 0例为对照组。SIRS组又按照预后分为存活组和死亡组。分别检测血小板数 (PLT)、D 二聚体 (DD)、蛋白C、蛋白S(PC、PS)、抗凝血酶Ⅲ (ATⅢ )、血栓调节蛋白 (TM)、组织纤溶酶原激活物(TPA)、纤溶酶原激活物抑制物 (PAI 1)、凝血酶原时间 (PT)、凝血酶时间 (TT)、活化部分凝血活酶时间(APTT)、纤维蛋白原 (FBG) 12项涉及到与凝血功能有关的实验室指标。结果　 (1)SIRS组中TT、APTT、PT、DD、TM、PAI 1均高于非SIRS组对照组 (P <0 0 5 ) ;PC、PS、TPA、PLT、FBG均低于非SIRS组及对照组 (P <0 0 5 )。 (2 )ATⅢ在三组中差异无显著性 (P >0 0 5 )。 (3)DD、APTT和PAI 1在SIRS组中的死亡组与存活组相比显著升高 (P <0 0 5 ) ,并与预后有显著相关性 (P <0 0 1)。结论 (1)在SIRS时存在有凝血系统功能紊乱。 (2 )SIRS时凝血系统功能紊乱主要特征表现为各种促凝物质增加 ,机体抗凝物质减少 ,纤溶系统被抑制 ,而纤溶系统抑制在SIRS发生、发展过程中可能起到更加重要的作用。 (3)DD和PAI 1与SIRS患者的预后呈负相关。     

创伤后凝血功能障碍的相关因素研究进展

创伤后凝血功能障碍是导致病人死亡的重要原因,及时发现并祛除高危因素,方能有效地纠正凝血异常,降低创伤后病人死亡率。近年来国内外对创伤病人凝血功能障碍的研究多集中于创伤性凝血病,其他引起创伤后凝血功能障碍的相关因素则研究不多。就创伤性凝血病相关因素如颅脑损伤、抗菌药物使用、长期口服抗凝药物、长期饮酒、肝脏疾病等做一综述,以期对创伤后凝血功能障碍的因素做出全面的评估。     

观察加强药学干预对促进抗生素合理用药的效果

目的:探索促进抗生素合理用药中加强药学干预的价值.方法:本次研究于2019年1月-2020年10月在本院进行,选取64例服用抗生素患者为对象,将其随机单盲法分组,每组32例,对照组为常规指导,观察组采取加强药学干预,分析效果.结果:观察组出现不良反应少于对照组,观察组抗生素治疗时间、抗生素治疗花费、抗生素用药频度、药物...     

抗癫痫药物的毒副作用

癫痫患者需要长期服药治疗甚至终生服药、合并用药.抗癫痫药(AEDs)已证实对全身多系统均有一定的影响,在使用过程中易产生各种毒副作用,应受到临床医生的关注.本文从AEDs对皮肤结缔组织、心血管系统、消化系统、血液系统、神经系统、内分泌、代谢的不良反应,对认知功能的影响以及致畸、加重癫痫发作等方面,就其毒副作用进行综述.     

Inappropriate Medication Use as a Risk Factor for Self-Reported Adverse Drug Effects in Older Adults

OBJECTIVES: To determine the association between inappropriate medication use and self‐reported adverse drug effects (ADEs). DESIGN: Prospective cohort study with three annual mailed surveys. SETTING: Population‐based sample of Iowa Medicare beneficiaries. PARTICIPANTS: Cohort members (n=626) with established mobility disability and complete pharmacy dispensing records, continuous Medicare eligibility, and survey data. MEASUREMENTS: The number of unique drug ingredients dispensed and inappropriate use were assessed for the year before the ADE survey. Inappropriate medication use was defined according to published criteria: contraindicated drugs for elderly people, drug–disease interactions (constructed from linked Medicare claims), drug–drug interactions, and therapeutic duplications. An ADE was defined from the following question: “In the past 12 months, have you experienced an unwanted effect or side effect of a medication?” RESULTS: Of respondents to the ADE survey, 22.0% reported having experienced an ADE in the past year, and 322 (51.4%) received at least one potential inappropriate medication. Factors associated univariately with ADE self‐report were number of medications, number of mobility limitations, any inappropriate medication use, and each of the individual domain appropriateness indicators, as well as number of different domains of inappropriate use. The adjusted odds ratio for developing an ADE was 2.14 (95% confidence interval=1.26–3.65) for those with inappropriate use versus no inappropriate use. CONCLUSION: Efforts to reduce ADEs by reducing medication inappropriateness should be encouraged as a complement to efforts focused on reducing the number of medications prescribed.     

The Course of Adverse Effects of Nortriptyline and Venlafaxine in Elderly Patients with Major Depression

OBJECTIVES: To evaluate tolerability and course of adverse effects of antidepressants in elderly patients and to study the association between number and severity of adverse effects and age, physical comorbidity, antidepressant dose. and depression severity.
DESIGN: Double-blind, randomized controlled trial followed by an open treatment phase of 3 years.
SETTING: Psychiatric hospital in the Netherlands.
PARTICIPANTS: Eighty-one elderly depressed inpatients.
INTERVENTION: Patients were treated with venlafaxine or nortriptyline.
MEASUREMENTS: Frequency and severity of 43 individual adverse effects were assessed using the Symptom, Sign, Side-Effect Checklist. Severity of depression was assessed using the Montgomery Åsberg Depression Rating Scale.
RESULTS: Both antidepressants were tolerated well, with no differences in clinical effectiveness, and most adverse effects decreased with time. The number and severity of adverse effects was not related to age or physical comorbidities. There was a significant relationship between the severity of depression and the severity of adverse effects, although the relationship between the dose of the antidepressant and the severity of the adverse effects was of only borderline statistical significance.
CONCLUSION: Elderly patients tolerated venlafaxine and nortriptyline well, and most adverse effects decreased with time as the depression improved. Age and physical comorbidities were not related to number and severity of adverse effects.     

利尿剂相关的肾损害

利尿剂是临床常用药物，广泛应用于利尿消肿、降压和脑水肿等治疗。利尿剂可直接或间接导致肾脏功能和组织学改变。利尿剂可通过细胞外容量的减少、人球和出球小动脉张力的改变和球一管反馈等机制导致肾血流量的减少和肾小球滤过率(GFR)的下降。利尿剂还可引起急性间质性肾炎、肾小管堵塞等肾脏损害；长期使用利尿剂可导致肾结石、尿沉渣异常和低钾性肾病等慢性改变，所以临床医生必须重视和避免利尿剂的肾毒性作用。     

Adverse Effects of GLP-1 Receptor Agonists

Glucagon-like peptide-1 (GLP-1) receptor agonists are a class of injective anti-diabetic drugs that improve glycemic control and many other atherosclerosis-related parameters in patients with type 2 diabetes (T2D). However, the use of this relatively new class of drugs may be associated with certain adverse effects. Concerns have been expressed regarding the effects of these drugs on pancreatic and thyroid tissue, since animal studies and analyses of drug databases indicate an association of GLP-1 receptor agonists with pancreatitis, pancreatic cancer, and thyroid cancer. However, several meta-analyses failed to confirm a cause-effect relation between GLP-1 receptor agonists and the development of these adverse effects. One benefit of GLP-1 receptor agonists is that they do not cause hypoglycemia when combined with metformin or thiazolidinediones, but the dose of concomitant sulphonylurea or insulin may have to be decreased to reduce the risk of hypoglycemic episodes. On the other hand, several case reports have linked the use of these drugs, mainly exenatide, with the occurrence of acute kidney injury, primarily through hemodynamic derangement due to nausea, vomiting, and diarrhea. The most common symptoms associated with the use of GLP-1 receptor agonists are gastrointestinal symptoms, mainly nausea. Other common adverse effects include injection site reactions, headache, and nasopharyngitis, but these effects do not usually result in discontinuation of the drug. Current evidence shows that GLP-1 receptor agonists have no negative effects on the cardiovascular risk of patients with T2D. Thus, GLP-1 receptor agonists appear to have a favorable safety profile, but ongoing trials will further assess their cardiovascular effects. The aim of this review is to analyze critically the available data regarding adverse events of GLP-1 receptor agonists in different anatomic systems published in Pubmed and Scopus. Whenever possible, certain differences between GLP-1 receptor agonists are described. The review also provides the reader with structured data that compare the rates of the most common adverse effects for each of the various GLP-1 receptor agonists.     

Modelling the 3-year risk of myocardial infarction among participants in the Data Collection on Adverse Events of Anti-HIV Drugs (DAD) study

Objectives

To estimate the 3‐year risk of myocardial infarction (MI) among participants in the Data Collection on Adverse Events of Anti‐HIV Drugs (DAD) study.

Methods

Conventional cardiovascular risk equations were applied to baseline data from the DAD study to estimate the 3‐year risk of MI. Best estimates were obtained by simply applying the risk equations, with upper and lower limits based on worst case and optimistic case scenarios. Three‐year risks of AIDS or death were also estimated based on a prognostic scoring system for patients receiving antiretroviral (ARV) treatment, and on estimated AIDS rates in untreated people with HIV for those patients not on ARVs or if they were to cease ARVs.

Results

Analyses were based on 17 600 patients (24.3% female) recruited into the DAD study with baseline data and no previous MI. The overall 3‐year risk of MI was estimated to be 0.72% (lower limit 0.35, upper limit 1.12%), corresponding to a total predicted 127 (65–197) MIs over a 3‐year follow‐up period. The risk was much greater for men than women (0.92% vs. 0.07%), with only three (2–8) MIs predicted in women. The 3‐year risk of MI was estimated to increase from 0.30% (0.20–0.38%) in ARV naive patients to 1.07% (0.43–1.77%) in patients receiving ARVs from all three drug classes. The estimated 3‐year risk of AIDS or death was in the range 6.2% to 11.1% in patients receiving ARVs if they continued treatment, and 22.5% to 29.4% if they ceased ARVs.

Discussion

These models suggest that although the increase in relative risk of MI as a result of ARV treatment may be as high as threefold in a worst case scenario, the absolute risk is modest with a best estimate of 3‐year risk less than or equal to 1% in all groups of patients, and is outweighed by the benefits of ARV treatment in terms of reduced risk of AIDS and death in most patients. As estimates are based on models not validated for people receiving ARV drugs, all estimates should be interpreted cautiously.

     

利尿剂的不良反应及对心力衰竭预后影响的研究进展

目前在临床上利尿剂仍为心力衰竭治疗的一线药物,其可迅速减轻心力衰竭患者水钠潴留,明显缓解症状并消除水肿,但长期、大量、不恰当地使用利尿剂可以产生许多不良反应。已有研究表明长期使用利尿剂可能增加部分心力衰竭患者死亡危险,但目前尚无利尿剂对心力衰竭病死率影响的确切结论。     

Clozapine-Induced Myocarditis: Recognizing a Potentially Fatal Adverse Reaction

A 46-year-old man with a history of paranoid schizophrenia was admitted with a recurrence of psychotic symptoms. Improvement was noted after the initiation of clozapine. After 2 weeks of clozapine therapy, chest pressure and abnormal cardiac biomarkers (in the presence of a normal coronary angiogram) raised suspicion of myocarditis. That diagnosis was confirmed by means of cardiac magnetic resonance imaging. Discontinuation of the clozapine led to resolution of the cardiac symptoms. Clozapine-induced myocarditis is rare and can be missed for lack of specific clinical findings. In order to prevent disease progression and a possibly fatal outcome, early recognition of the condition and prompt discontinuation of clozapine are necessary.     

Haematological profiles after Intensive phase of Anti Koch Treatment with special emphasis on bone marrow changes

BackgroundTuberculosis remains a major public health problem in various parts of the world. It leads to various haematological changes. Study of these haematological changes will help better patient management.Objective & methodsIt is to evaluate haematological changes in tuberculosis patients and compare the result with special emphasis to bone marrow changes as active case search is sharply decreasing the miliary tuberculosis. It is also to evaluate the patients with before and after the Intensive Phase of Anti Koch Treatment. Sputum positive and sputum negative tuberculosis patients confirmed by other ancillary techniques were included into this study. It is conducted at a tertiary level hospital in rural area.ResultIn this study bone marrow hypercellularity was of erythroid series with only 1.92% patients showed granuloma in bone marrow aspiration. In addition to bone marrow changes, significant changes were evident in haemoglobin level, Erythrocyte Sedimentation Rate (ESR) Total White Blood Cell count and RBC count.DiscussionIn majority cases this study showed Erythroid Hyperplasia. It is sharp contrast with other study where myeloid hyperplasia was evident. This study also differs from other study where high number of bone marrow granuloma was reported. In this study only 1.92% cases showed bone marrow granuloma. This study also documented higher number of anaemic cases mostly because of the institute serves poor and tribal population.ConclusionIn our study the cases showing granuloma and hyperplasia of myeloid series were limited. With introduction of Directly Observed Treatment and house to house active case search helped to sharply decrease bone marrow granuloma by limiting multi-organ spread. This study showed, ESR level may be considered as prognostic parameters of tuberculosis.     

Adverse effects of amiodarone therapy in adults with congenital heart disease

Objective: Amiodarone is a highly effective antiarrhythmic therapy, however its tox‐ icity profile often limits treatment. This is particularly relevant in adults with congeni‐ tal heart disease (CHD), who are often young and in whom other antiarrhythmic agents commonly fail or are contraindicated. We sought to determine incidence and predictors of adverse effects caused by amiodarone in adult CHD (ACHD).
Design: A retrospective review of patients with moderate to complex ACHD treated with amiodarone at our center between 2000 and 2017 was performed. Incidence and predictors of adverse effects were described. Efficacy of amiodarone therapy in controlling the clinical arrhythmia was assessed as complete, partial, or failed.
Results: Amiodarone was prescribed in 57 patients of 902 ACHD patients reviewed (6%), for a mean duration of 2.7 ± 4.3 years. Significant adverse effects occurred in 56%, most commonly thyroid dysfunction, with amiodarone‐induced thyrotoxicosis (AIT) in 30% and amiodarone‐induced hypothyroidism in 14%. AIT frequently led to arrhythmia exacerbation and occurred most in those with Fontan anatomy. Severe dermatological effects were seen in 7% and bradycardia requiring pacing in 5%. Interstitial lung disease, peripheral neuropathy and alopecia were observed in single cases. Amiodarone toxicity led to discontinuation of the drug in 42%. Amiodarone was highly effective when tolerated, however, achieving complete arrhythmia con‐ trol in 63%, partial control in 35%, with failure to control in only one patient.
Conclusions: Amiodarone therapy is effective in moderate to complex ACHD pa‐ tients, but is frequently limited by adverse effects. ACHD patients seem especially vulnerable to thyroid dysfunction, with Fontan patients in particular at increased risk of AIT.