Local toxicity of different drugs after intramuscular or intralipomatous injection in pigs: serum concentrations after three different formulations of cis(Z)-clopenthixol

Findings made by computerized tomography scanning of pelvis of patients suggested that the majority of injections intended to be intramuscular in fact are delivered in the fat tissue. This finding has raised the question what difference it makes when drugs are injected intramuscularly or intralipomatously. We have studied local toxicity after intramuscular or intralipomatous injection of different drugs in pigs, which have a subcutaneous layer of fat comparable to that of man. The pigs were killed 1, 3, 7 or 14 days after injection of antibiotics, vitamins, neuroleptics, diazepam, digoxin, pentazocine, sulphadimidine and vehicles. The tissues at the injection site were examined macro- and microscopically. In another series of experiments an aqueous or two different oily preparations of the neuroleptic drug cis(Z)-clopenthixol were given intramuscularly or intralipomatously to pigs and a series of blood samples were taken for drug level determination. The tissue examinations showed that all drugs causing local muscle damage after intramuscular injection caused considerably less extensive damage with a faster regeneration after intralipomatous injection. The pharmacokinetic study showed that there was virtually no difference between plasma-concentration-time curves after intramuscular or intralipomatous injection. Our findings indicate that intralipomatous injection of irritating drugs is better tolerated than intramuscular injection since intralipomatous injection causes less local toxicity. Our findings also suggest that the pharmacokinetics are not different. However, further studies are required to substantiate whether the findings are of general relevance.     

Local Toxicity of Different Drugs after Intramuscular or Intralipomatous Injection in Pigs: Serum Concentrations after Three Different Formulations of cis(Z)–Clopenthixol

Abstract: Findings made by computerized tomography scanning of pelvis of patients suggested that the majority of injections intended to be intramuscular in fact are delivered in the fat tissue. This finding has raised the question what difference it makes when drugs are injected intramuscularly or intralipomatously. We have studied local toxicity after intramuscular or intralipomatous injection of different drugs in pigs, which have a subcutaneous layer of fat comparable to that of man. The pigs were killed 1, 3, 7 or 14 days after injection of antibiotics, vitamins, neuroleptics, diazepam, digoxin, pentazocine, sulphadimidine and vehicles. The tissues at the injection site were examined macro– and microscopically. In another series of experiments an aqueous or two different oily preparations of the neuroleptic drug cis(Z)–clopenthixol were given intramuscularly or intralipomatously to pigs and a series of blood samples were taken for drug level determination. The tissue examinations showed that all drugs causing local muscle damage after intramuscular injection caused considerably less extensive damage with a faster regeneration after intralipomatous injection. The pharmacokinetic study showed that there was virtually no difference between plasma–concentration–time curves after intramuscular or intralipomatous injection. Our findings indicate that intralipomatous injection of irritating drugs is better tolerated than intramuscular injection since intralipomatous injection causes less local toxicity. Our findings also suggest that the pharmacokinetics are not different. However, further studies are required to substantiate whether the findings are of general relevance     

改良乳腺癌根治术的疗效观察

目的 对乳腺癌治疗中改良乳腺癌根治术的临床疗效进行观察.方法 选取我院于2000-2012年收治乳腺癌患者42例,采用改良乳腺癌根治术展开治疗,并于术后进行化疗、放疗等辅助综合治疗.结果 42例患者手术后恢复情况均良好,无胸肌萎缩、皮瓣坏死、皮下积液或水肿等并发症发生,3年内生存率为100%.结论 在对乳腺癌进行外科治疗时,改良乳腺癌根治术具有确切临床疗效.在手术中展开规范操作,术后进行综合治疗可有效抑制各种并发症发生,能大大提高患者生活质量,值得在临床中推广.     

应用自体颗粒脂肪纯化及游离移植矫正面部外观缺陷

目的探讨简便的自体脂肪颗粒纯化的方法,总结自体脂肪颗粒游离移植矫正颜面部外观缺陷的经验。方法应用一种简便的脂肪颗粒纯化技术以及脂肪颗粒注射方法对患者面部外观缺陷进行治疗,术后进行随访。结果脂肪颗粒的成活率为20%～90%,其高低与脂肪颗粒的损伤程度、是否进行了提纯、术后加压制动、注射部位的活动程度以及局部血运是否良好有关。大部分患者对外观的改善满意。结论本研究中采用的颗粒脂肪纯化和移植技术能提升脂肪移植的成活率,可有效地矫正面部外观的缺陷。     

皮下注射低分子肝素局部按压与否对皮下出血的影响

目的探讨低分子肝素（LMWH）皮下注射经局部按压与否对皮下出血的关系。方法选择47例冠心病行皮下注射LMWH的患者,用自身对照法,即右腹部注射后局部压迫3-5min,左腹部注射后局部不压迫。观察皮下注射后1、3、7d局部皮下出血的例、性质及面积。结果观察组与对照组皮下出血例、性质、面积比较,P〈0.01,差异具有统计学意义。结论采用局部不按压方法可以显著降低皮下出血的发生率及皮下出血的程度。     

初诊2型糖尿病胰岛素强化治疗对血糖、游离脂肪酸及血脂变化的对比研究

目的观察初诊2型糖尿病患者，应用连续胰岛素皮下输注（CSII）及多次胰岛索皮下注射（MDI）强化治疗2周对血糖、游离脂肪酸（FFA）、血脂变化的对比研究。方法选择初诊2型糖尿病88例随机分为CSII组44例及MDI组44例。分别在治疗前和胰岛素强化治疗2周结束后，同时测定空腹血糖、游离脂肪酸及血脂。结果CSII组和MDI组治疗前后游离脂肪酸、血清胆固醇（Tc）、甘油三酯（TG）、低密度脂蛋白（HDL—C）、载脂蛋白B（ApoB）均明显下降（P〈0．05），高密度脂蛋白胆固醇（HDL—C）及载脂蛋白A（ApoA）均上升。结论短期强化治疗可改善2型糖尿病的血糖、游离脂肪酸及脂质代谢。     

Single injection of ONO-1301-loaded PLGA microspheres directly after ischaemia reduces ischaemic damage in rats subjected to middle cerebral artery occlusion

Objectives ONO‐1301 was developed as a novel long‐acting prostacyclin agonist with thromboxane synthase inhibitory activity. In this study, we investigated the therapeutic time window of oral ONO‐1301 and the effect of a single subcutaneous injection of ONO‐1301‐loaded poly(lactide‐co‐glycolide) (PLGA) microspheres (ONO‐1301 PLGA MS) on infarction volume, functional deficits and plasma ONO‐1301 levels following a 1 h middle cerebral artery occlusion (MCAO) in rats. Methods Rats were treated with ONO‐1301 (3 mg/kg) orally twice‐daily starting 1 (directly), 6 or 24 h after MCAO. Rats received a single subcutaneous injection of ONO‐1301 PLGA MS (10 mg/kg) directly after MCAO. Neurological scores were evaluated directly after, 1 and 6 h, 1, 2, and 3 days after MCAO. Infarct volume, oedema and plasma ONO‐1301 levels were measured three days after MCAO. Key findings Neurological scores, oedema and infarct volume were all significantly improved in rats repeatedly treated with oral ONO‐1301 and subcutaneous ONO‐1301 PLGA MS directly after MCAO. Plasma ONO‐1301 levels were significantly lower in rats treated directly after MCAO (either with ONO‐1301 or ONO‐1301 PLGA MS) than in rats treated 6 h or 24 h after MCAO. Conclusions ONO‐1301 PLGA MS subcutaneous treatment directly after MCAO showed a neuroprotective effect as well as oral ONO‐1301. This treatment should be clinically more convenient than ONO‐1301 oral administration since it is delivered as a single treatment after MCAO.     

Clinical pharmacokinetics of depot leuprorelin

Leuprorelin acetate is a synthetic agonist analogue of gonadotropin-releasing hormone. Continued leuprorelin administration results in suppression of gonadal steroid synthesis, resulting in pharmacological castration. Since leuprorelin is a peptide, it is orally inactive and generally given subcutaneously or intramuscularly. Sustained release parenteral depot formulations, in which the hydrophilic leuprorelin is entrapped in biodegradable highly lipophilic synthetic polymer microspheres, have been developed to avoid daily injections. The peptide drug is released from these depot formulations at a functionally constant daily rate for 1, 3 or 4 months, depending on the polymer type [polylactic/glycolic acid (PLGA) for a 1-month depot and polylactic acid (PLA) for depot of >2 months], with doses ranging between 3.75 and 30mg. Mean peak plasma leuprorelin concentrations (C(max)) of 13.1, 20.8 to 21.8, 47.4, 54.5 and 53 microg/L occur within 1 to 3 hours of depot subcutaneous administration of 3.75, 7.5, 11.25, 15 and 30 mg, respectively, compared with 32 to 35 microg/L at 36 to 60 min after a subcutaneous injection of 1mg of a non-depot formulation. Sustained drug release from the PLGA microspheres maintains plasma concentrations between 0.4 and 1.4 microg/L over 28 days after single 3.75, 7.5 or 15mg depot injections. Mean areas under the concentration-time curve (AUCs) are similar for subcutaneous or intravenous injection of short-acting leuprorelin 1mg; a significant dose-related increase in the AUC from 0 to 35 days is noted after depot injection of leuprorelin 3.75, 7.5 and 15mg. Mean volume of distribution of leuprorelin is 37L after a single subcutaneous injection of 1mg, and 36, 33 and 27L after depot administration of 3.75, 7.5 and 15mg, respectively. Total body clearance is 9.1 L/h and elimination half-life 3.6 hours after a subcutaneous 1mg injection; corresponding values after intravenous injection are 8.3 L/h and 2.9 hours. A 3-month depot PLA formulation of leuprorelin acetate 11.25mg ensures a C(max) of around 20 microg/L at 3 hours after subcutaneous injection, and continuous drug concentrations of 0.43 to 0.19 microg/L from day 7 until before the next injection. Recently, an implant that delivers leuprorelin for 1 year has been evaluated. Serum leuprorelin concentrations remained at a steady mean of 0.93 microg/L until week 52, suggesting zero-order drug release from the implant. In general, regular or depot leuprorelin treatment is well tolerated. Local reactions are more common after application of the 3- or 4-month depot in comparison with the 1-month depot.     

安脱达尘螨疫苗治疗儿童过敏性哮喘的疗效及安全性评价

目的:评价安脱达尘螨变应原疫苗治疗过敏性哮喘的疗效及安全性。方法:采用自身对照方法,对125例尘螨过敏性哮喘患儿皮下注射特异性免疫疫苗(安脱达),记录治疗前后哮喘症状、合并用药评分,同时计算与免疫相关不良反应发生率,评价其安全性。结果:脱敏治疗1年后125例患儿哮喘症状明显改善,合并用药计分明显减少。80.0%(100/125)的哮喘患儿伴发过敏性鼻炎,脱敏治疗1年后鼻炎症状明显改善。23.2%的患儿因哮喘症状明显好转,在治疗第26周末自行停用合并药物,第52周末随访病情,哮喘复发率为10.3%(3/29)。125例患儿总计接受免疫治疗注射2676次,43例患儿出现100例次局部不良反应,局部不良反应的发生率为3.7%(100/2676),14例患儿出现23例次全身不良反应,全身不良反应发生率0.9%(23/2676),未出现致死性全身不良反应。结论:标准化变应原进行脱敏治疗在规范化操作下是一种安全有效的治疗方法。     

局部皮下注射神经妥乐平治疗神经源性疼痛的临床观察

目的通过临床观察评价神经妥乐平局部皮下注射治疗神经源性疼痛的疗效与安全性。方法21例神经源性疼痛患者皮下注射神经妥乐平3.6 U/次,1周2次,连续3周为1个疗程,采用疼痛视觉模拟评分法(VAS法)评定疗效并进行统计学分析。结果治疗后患者疼痛强度显著性降低(P<0.05),未出现明显不良反应。结论神经妥乐平皮下注射治疗神经源性疼痛,有效、安全、简便。     

脂肪瘤与皮下脂肪细胞药理学特性差异的研究

目的研究脂肪瘤细胞与皮下脂肪细胞药理学特性的差异，为探讨脂肪瘤的形成机制和非手术治疗的方法提供理论依据。方法用不同浓度的异丙肾上腺素、肾上腺素、去甲肾上腺素和ＢＲＬ３７３４４分别激动离体人脂肪瘤和皮下脂肪细胞上的β受体，根据β受体激动后产生的ｃＡＭＰ的量效曲线和最大效应，分析脂肪瘤细胞和皮下脂肪细胞上β受体药理学特性的差异。结果几种不同的β受体激动剂脂肪瘤细胞上的β受体后产生ｃＡＭＰ的最大效应均小于正常皮下脂肪细胞。几种激动剂激动２种脂肪细胞上的β受体作用强度顺序相同，即异丙肾上腺素＞肾上腺素＞去甲肾上腺素＞ＢＲＬ３７３４４。ＢＲＬ３７３４４对２种脂肪细胞上β受体的激动作用都很微弱，且最大效应间无显著差异。结论脂肪瘤细胞上的β肾上腺素受体对β受体激动剂的敏感性低于正常皮下脂肪细胞。ＢＲＬ３７３４４对人脂肪瘤细胞和皮下脂肪细胞上β受体的激动作用微弱。     

The parenteral controlled release of liposome encapsulated chloroquine in mice

Free (0.6 mg), and liposome encapsulated chloroquine (0.6, 3 mg), were injected intraperitoneally, intramuscularly and subcutaneously in mice. Intraperitoneal administration of liposome-encapsulated chloroquine resulted in high and long lasting concentrations of chloroquine in the blood compared with intraperitoneal administration of free chloroquine. After administration of the liposome-encapsulated chloroquine the concentrations in the spleen were also higher, indicating that chloroquine liposomes reached the blood compartment intact after intraperitoneal administration. After intramuscular and subcutaneous administration the chloroquine liposomes acted as a local depot, giving a slower release from the subcutaneous fat layer than from the muscle depot. After the 0.6 mg dose a burst effect was found at about 7 h in most of the animals; this was not found after the 3 mg dose. This finding and the slower release after the 3 mg dose than after the 0.6 mg dose could be explained by the formation of aggregates after the injection.     

Factors predicting retention in treatment: 10-year experience of a methadone maintenance treatment (MMT) clinic in Israel

The aims were to identify predictors of treatment retention in an Israeli methadone maintenance treatment (MMT) clinic, and to compare the findings to other international settings. We prospectively studied 492 patients admitted since 1993 through 10 years to an Israeli MMT clinic associated with a university-affiliated tertiary care medical center. Analyses (Kaplan Meier and Cox regression) included methadone dose and urinalysis results (for methadone, cocaine, opiates, benzodiazepines, THC, amphetamines) of each patient in the first month and after 1 year in treatment (or during the last month if the stay was >3 months and <1 year) and patients' characteristics (modified ASI). The 1-year retention rate was 74.4%; 65.8% stopped opiate abuse after 1 year in treatment. On admission, 13.6% of patients had used cocaine: there was a net decrease of 61.6% after 1 year. Factors predicting prolonged retention in MMT treatment (Cox regression) were daily methadone dose of 100mg or greater, negative urine for opiates after 1 year, and being a parent on admission. We conclude that our good outcome results (high rate of retention after 1 year (74.4%), high proportion of opiate abuse cessation (65.8%), and net reduction in cocaine abuse, similar to normal standards in other MMT clinics elsewhere in the world, justify the expansion of the MMT clinic network in Israel in order to make treatment available to all those who need it. A protocol favoring higher methadone dosage as appropriate is recommended.     

Enhancement of the results of neck liposuction with the FAMI technique

Submental liposuction is an excellent procedure for improving the aging neck by reducing the cervicomental angle and increasing the definition of the mandibular border. However, it does not address the loss of volume of the chin and perioral areas caused by atrophy of hard and soft tissues. In this study, thirty patients underwent concomitant submental tumescent liposuction and fat augmentation with the FAMI (fat autograft muscle injection) technique in order to assess short-term results and complications associated with these two relatively noninvasive procedures. All patients had improvement in the cervicomental border, a smoother mandibular border, and a more proportioned chin following 3-5 days of swelling. Patients followed for 6 months to one year had long term retention of fat. There were no significant complications. In this preliminary series, submental tumescent liposuction with FAMI provided enhanced aesthetic results with little downtime and minimal complications.     

改良皮下注射硼替佐米在多发性骨髓瘤治疗中的临床价值研究

目的 分析改良皮下注射硼替佐米在多发性骨髓瘤治疗中的临床价值.方法 72例多发性骨髓瘤患者,采用随机抽样法分为参照组和实验组,每组36例.两组患者均使用硼替佐米进行治疗,参照组患者采用传统常规注射,研究组患者采用改良皮下注射.比较两组患者药物注射后躯体疼痛程度和注射药物后不良事件发生情况.结果 药物注射后,研究组患者视...     

大隐静脉曲张微创治疗进展

大隐静脉曲张(GSVV)是一张常见疾病,主要表现为下肢浅静脉迂曲扩张,常合并溃疡、湿疹、静脉炎等。由于静脉血液动力学改变,使静脉主干和皮肤毛细血管压力增高, 导致皮肤皮下缺血缺氧和营养缺乏, 皮肤色素沉着、 纤维化、 皮下脂肪硬化、 皮肤萎缩, 最终形成静脉性溃疡;随着医疗技术的发展,各种微创治疗方式应用于GSVV,该文就GSVV治疗现状予以综述。     

An in vivo method for the quantitative evaluation of local anesthetics

We describe a mouse model for evaluation of skin anesthesia after infiltration of local anesthetic. The method involves subcutaneous injection of the anesthetic over the abdomen, and monitoring the vocalization response to electrical stimulus as a measure of analgesia. Prior to drug injection, the vocalization threshold was determined. Mice that vocalized at < or = 8 mA were included in the study. The model was tested using representative agents of the two classes of local anesthetics, bupivacaine, an amide, and chloroprocaine, an ester. The time course and dose response were assessed after injection. The median analgesic time was 15, 40, and 55 min for 0.015%, 0.0625%, and 0.25% bupivacaine and 30, 50, and 55 min for 0.125%, 0.25%, and 2.0% chloroprocaine, respectively. Statistical analysis of the data showed that this method is sufficiently sensitive to detect differences between the dose and duration of local anesthesia (p<0.05, by log rank test of the survival curves). To further validate the model, we compared the duration of anesthesia between the 0.5% bupivacaine and a new long-acting liposomal formulation of 2% bupivacaine. The results showed that the new formulation significantly prolonged the duration of anesthesia (p<0.05). This simple and reliable method may facilitate research on the pharmacology of infiltration anesthesia and the development of new local anesthetics and/or formulations.     

Influenza Vaccination and Warfarin Anticoagulation: A Comparison of Subcutaneous and Intramuscular Routes of Administration in Elderly Men

Study Objectives . To determine if subcutaneous administration of influenza vaccine is as immunogenic as the intramuscular route, and to evaluate the frequency of local adverse events associated with both routes in elderly anticoagulated men. Design . Single-blind, prospective study of consecutively enrolled subjects. Setting . Ambulatory clinic at a university-affiliated Veterans Affairs medical center. Patients . Twenty-six men age 60 years or older, receiving therapeutic dosages of warfarin. Interventions . Subjects were randomized to receive either intramuscular or subcutaneous injection of a standard trivalent influenza vaccine. Measurements and Main Results . Serum antibody titers to the vaccine's components were measured at baseline, and 6 weeks and 4 months after vaccination. Both routes of administration induced comparable serum antibody titers. There were no differences in adverse events at administration sites between routes of administration. Conclusions . Elderly individuals are able to mount an immune response to influenza vaccine and produce antibody concentrations deemed protective. The routes of administration are similarly effective at inducing an immune response. The intramuscular route in anticoagulated elderly men does not commonly result in local bleeding complications.     

宫颈癌患者卵巢移位部位的探讨（附46例分析）

目的：探讨年轻宫颈癌患者行卵巢移位术对卵巢功能的影响及移位于皮下,腹腔两组卵巢移位术患者的临床比较,方法：46例年轻官颈癌患者行根治术的同时进行了卵巢移位,其中卵巢移位于皮下者24例,移于腹腔内22例,观察对比两组患者的临床表现,及术前、术后1个月,6个月,1年分别抽血查FSH、LH、E2。结果：皮下组有18例出现周期性腹痛,15例出现局部肿块,腹腔组均无,两组比较有显著性差异（P＜0．01）;皮下组2例出现卵巢囊肿,4例出现急发生腹痛,6例出现更年期症状,腹腔组4例出现更年期症状,无卵巢囊肿,急性腹痛发生,两组比较无显著性差异（P＞0．05）,皮下组有3例术后1个月FSH,LH升高,1例E2下降达绝经后水平;腹腔组有2例术后1个月FSH、LH升高达绝经后水平,术后6个月时复查均恢复正常,两组比较无显著性差异（P＞0．05）。结论：年轻宫颈癌患者行卵巢移位术后能保持良好的卵巢功能,从临床表现上看,保留的卵巢移位于腹腔内优于移位于皮下。     

Human growth hormone: New delivery systems, alternative routes of administration, and their pharmacological relevance

The availability of recombinant human growth hormone (GH) has broadened its range of clinical applications. Approved indications for GH therapy include treatment of growth hormone deficiency (in children and in adults), Turner syndrome, Prader-Willi syndrome, chronic renal insufficiency and more recently, idiopathic short stature in children, AIDS-related wasting and fat accumulation associated with lipodystrophy in adults. Therapy with GH usually begins at a low dose and is gradually titrated to obtain optimal efficacy while minimizing side effects. It is usually administered on a daily basis by subcutaneous injection, since this was considered to impact upon patient compliance, extended-release GH preparations were developed and new delivery platforms - e.g., auto-injectors and needle-free devices - were introduced in order to improve not only compliance and convenience but also dosing accuracy. In addition, alternative less invasive modes of administration such as the nasal, pulmonary and transdermal routes have also been investigated. Here, we provide an overview of the different technologies and routes of GH administration and discuss the principles, limitations and pharmacological profiles for each approach.