The safety and efficacy of an extravascular, water-soluble sealant for vascular closure: initial clinical results for Mynx.

OBJECTIVE: The purpose of this study was to evaluate the hemostatic efficacy and safety of the Mynx extravascular sealant for femoral artery closure. BACKGROUND: The Mynx device is an extra-arterial vascular closure technology utilizing a water-soluble, porous, polyethylene glycol matrix that immediately seals the arteriotomy by rapidly absorbing subcutaneous fluids and expanding in the tissue tract and then, resorbs within 30 days. METHODS: The Mynx study was a prospective, multicenter, single-arm clinical investigation conducted at five European centers. The safety and effectiveness of the Mynx device was evaluated in patients following diagnostic or interventional endovascular procedures performed through 5 Fr, 6 Fr, or 7 Fr introducer sheaths in the common femoral artery. The primary safety endpoint was the combined rate of major complications within 30 days (+/-7 days). The primary efficacy endpoints were time to hemostasis and time to ambulation. RESULTS: Patient enrollment included 190 patients with 50% having undergone diagnostic catheterization and 50% interventional procedures with a mean activated clotting time of 221 sec. One (0.5%) major vascular complication (transfusion) occurred in one patient. No device-precipitated complications associated with serious clinical sequelae were reported. Mean (+/- standard deviation) times to hemostasis and ambulation were 1.3 +/- 2.3 min and 2.6 +/- 2.6 hr, respectively. There was no significant difference in median times to hemostasis between diagnostic and interventional patients (0.5 vs. 0.6 min). CONCLUSIONS: The initial experience with the extra-arterial Mynx closure technology supports hemostatic safety and efficacy in patients undergoing diagnostic and interventional catheterization procedures.     

Sample preparation and radioimmunoassay for circulating free and antibody-bound insulin concentrations in insulin-treated diabetics: a re-evaluation of methods

Methods for blood sample preparation and radioimmunoassay of free and antibody-bound serum or plasma insulin concentrations, using polyethylene glycol (PEG) solution to precipitate bound insulin, have been evaluated and compared. Method A was rapid mixing of whole blood with PEG, followed by separation of bound insulin by centrifugation into Ficoll; method B was rapid PEG addition to whole blood, followed by centrifugation alone; method C was conventional PEG addition to thawed plasma or serum, followed by centrifugation to remove bound insulin. Method A was found to have acceptable performance and reproducibility; serum free insulin levels were not significantly different from those measured by the simpler method B. In samples from insulin-dependent diabetics, serum free insulin was significantly higher and bound insulin significantly lower in method A compared to the conventional method C. However, in samples from non-diabetics there was no significant difference between methods A and C. Spurious results were obtained by addition of PEG and assay of plasma and serum samples after either freezing and thawing or incubation at 37 degrees C for 2h, compared to PEG addition and assay of fresh plasma or serum samples. We conclude that conventional, delayed addition of PEG to plasma or serum may result in redistribution of free and bound insulin and that values more representative of in vivo blood insulin levels are obtained by rapid PEG addition methods.     

复方聚乙二醇用于内镜检查前结肠准备的多中心随机对照临床研究

目的验证评价复方聚乙二醇进行结肠准备的清肠效果和安全性。方法对106例服用聚乙二醇4000口服溶液用粉(研究组)及105例甘露醇(对照组)作为结肠镜前准备的患者进行的多中心、开放、随机、对照临床研究，以整体结肠准备质量为主要疗效评价指标，并记录不良事件。结果研究组结肠整体准备的总有效率为92．4％(98／106)，对照组为80．0％(84／105)，研究组高于对照组(P=0．016)。研究组不良事件发生率为8．5％(9／106)，6例为恶心呕吐，3例为用药后实验室检查异常，均在短时间内自然缓解，对肠镜检查无影响，未发生严重不良事件。对照组不良事件发生率为14．3％(15／105)，4例为恶心呕吐等消化道症状，1例为胸闷，10例为用药后实验室检查异常，并出现1例严重不良事件。两组间不良事件发生率无显著性差异。结论复方聚乙二醇4000口服溶液用粉是用于各种临床检查肠道准备的安全有效的药物。     

Randomized Cross-Over Trial of Polyethylene Glycol Electrolyte Solution and Water for Colostomy Irrigation

PURPOSE: Water for colostomy irrigation is largely absorbed by the colon, which may result in less efficient expulsion of stool. This study compared the outcome of colonic cleansing with water and polyethylene glycol solution.METHODS: In a cross-over study, 41 colostomy irrigators were randomly assigned to water or polyethylene glycol solution irrigation first and then the other regimen, each for one week. Patients recorded fluid inflow time, total washout time, cramps, leakage episodes, number of stoma pouches used, and satisfaction scores (Visual Analog Scale, 1–10: 1 = poor, and 10 = excellent). The median and interquartile range for each variable was calculated, and the two treatments were compared (Wilcoxons test).RESULTS: Eight patients failed to complete the study. Thirty-three patients (20 females; mean age, 55 (range, 39–73) years) provided 352 irrigation sessions: water (n = 176), and polyethylene glycol solution (n = 176). Irrigation was performed every 24, 48, and 72 hours by 17, 9, and 7 patients respectively, using 500 ml (n = 1), 750 ml (n = 2), 1,000 ml (n = 16), 1,500 ml (n = 11), 2,000 ml (n = 2), and 3,500 ml (n = 1) of fluid. The median and interquartile range for water vs. polyethylene glycol solution were: fluid inflow time (6 (range, 4.4–10.8) vs. 6.3 (range, 4.1–11) minutes; P = 0.48), total washout time (53 (range, 33–69) vs. 38 (range, 28–55) minutes; P = 0.01), leakage episodes (2.3 (range, 1.7–3.8) vs. 0.7 (range, 0.2–1); P < 0.001), satisfaction score (5.8 (range, 4–7.5) vs. 8.8 (range, 8.3–10); P < 0.001), and stoma pouch usage per week (75 (range, 45–80) vs. 43 (range, 0–80); P = 0.008). No difference was demonstrated for frequency of cramps (P = 0.24).CONCLUSIONS: Polyethylene glycol solution performed significantly better than water and may be a superior alternative fluid regimen for colostomy irrigation.Austin OBichere was supported by a grant from St. Marks Hospital/Northwick Park Institute for Medical Research and Dansac Limited.Poster presentation in part at the meeting of The American Society of Colon and Rectal Surgeons, San Diego, California, June 2 to 7, 2001, and presented at the meeting of the Association of Coloproctologists of Great Britain and Ireland, Harrogate, United Kingdom, June 25 to 27, 2001.     

不同渗透压液体洗胃对兔内环境和肺组织的影响

目的探讨不同渗透压液体洗胃对兔内环境和肺组织的影响。方法将32只日本长耳大白兔随机分为正常对照组(NC组)、清水组(CW组)、0.45%氯化钠溶液组(HS组)、0.9%氯化钠溶液组(NS组),每组8只。CW组、HS组、NS组分别用清水、0.45%氯化钠溶液和0.9%氯化钠溶液进行洗胃,NC组仅置胃管不洗胃。各组在置胃管前以及洗胃结束后(NC组在对应时间点)采血检测血电解质,计算血浆渗透压;然后用气栓法处死兔,取全肺检测肺系数,取右下肺行苏木精-伊红染色,光镜下观察肺组织病理学变化情况。结果洗胃前各组兔血电解质、血浆渗透压相比,差异无统计学意义。洗胃后,CW组和HS组血钠浓度、血浆渗透压显著下降(均P0.05);CW组、HS组和NS组血钾、血钙浓度显著下降(均P0.05)。CW组和HS组肺系数较另两组显著升高(均P0.05)。结论清水和0.45%氯化钠溶液洗胃可导致低钠、低钾和低钙,血浆渗透压下降,肺系数增加,诱发和加重肺水肿。0.9%氯化钠溶液洗胃可降低低钠血症发生率,减缓血钙下降速度,并对血浆渗透压、肺系数无明显影响。     

Employing a PLGA-TPGS based nanoparticle to improve the ocular delivery of Acyclovir

Delivering drugs via the ocular route has always been a challenge for poorly soluble drugs. The various anatomical and physiological barriers in the eye cavity hinder the residence of drugs within the corneal and precorneal regions. In this study, the nanosystem that could sufficiently deliver the poorly soluble Acyclovir topically via ocular route. Our nanosystem is composed of the biocompatible PLGA polymer stabilized with TPGS which possess a high emulsifying capacity and is also known as P-gp inhibitor. The optimized nanoparticles were prepared with 0.3% TPGS and had particle-size of 262.3?nm, zeta-potential of +15.14?mV. The physicochemical-characterization, ex vivo transcorneal permeation, ocular-irritation and Acyclovir ocular-availability, following topical ocular application of PLGA-NPs in rabbit eyes, were performed. The tested parameters and irritation by Draize’s test suggested the suitability and safety of PLGA-NPs for ocular use. An ultrahigh performance liquid chromatographic method was developed, validated, and applied to quantify Acyclovir in aqueous humor which was shown to be significantly higher (p?<?0.05) using the developed nanoparticles as compared to Acyclovir-aqueous suspension following their single topical ocular administration. Noticeable 2.78-, 1.71- and 2.2-times increased values of AUC_0–24h, t_1/2 (h) and MRT_0–24h were found, respectively, with the PLGA-TPGS-NPs as compared to ACY-AqS. These results demonstrate the superiority of delivering Acyclovir using a nanosystem compared to conventional methods.     

气相色谱法测定环孢素口服溶液中乙醇和丙二醇含量

目的：建立气相毛细管色谱法测定环孢素口服溶液中的乙醇和丙二醇含量;方法：色谱柱为TG-624(30 m × 0.25 mm × 1.4 μm),采用程序升温;进样口温度：200 ℃;检测器温度：220 ℃;柱流量：0.2 ml.min^-1;进样量：1 μl;进样方式：分流;分流比：20:1;载气：氮气;内标物为正丙醇,溶剂为二甲基亚砜。结果：乙醇在1.491 mg.ml^-1～3.479 mg.ml^-1的范围内,其峰面积与浓度呈良好线性关系,y=0.5376x-0.0422, r=0.9999;高、中、低三个浓度的加样回收率分别为99.6%、100.8%、99.5%;定量限为19.9 mg.ml^-1,检测限为6.0 mg.ml^-1;重复性和中间精密度的RSD分别为0.04%﹑0.33%。丙二醇在1.4639 mg.ml^-1～3.4157 mg.ml^-1的范围内线性关系良好,y=0.3924x-0.0152, r =0.9997;高、中、低三个浓度的加样回收率分别为101.3%、100.5%、100.6%;定量限为19.5 mg.ml^-1,检测限为5.8 mg.ml^-1;重复性和中间精密度的RSD分别为0.60%﹑0.74%。结论：经验证,该方法简便易行,线性、专属性、耐用性、精密度、稳定性良好,可用于测定环孢素口服溶液中乙醇和丙二醇含量。     

Differences in clinical chemistry values according to the use of two laxatives for colonoscopy

Objectives

Polyethylene glycol–electrolyte lavage solutions (PEG–ELSs) and sodium phosphate formulations (NaPs) are two major colon cleansing laxatives used in preparation for endoscopic examinations of the gastrointestinal tract. PEG–ELSs are osmotically balanced preparations, whereas NaPs are hyperosmotic purgatives. This study aimed to evaluate the effects of these two laxatives on routine chemistry tests.

Design and methods

We retrospectively reviewed 9366 clinical records of patients who had health checkups with or without colonoscopy from July 2010 to June 2011. We compared the values of 19 clinical chemistry parameters in the NaPs group (n = 3239) and the PEG–ELSs group (n = 1279) with those of controls (without colonoscopy, n = 4848).

Results

Compared with controls, the NaPs group had higher mean values of inorganic phosphate, sodium, chloride, creatinine, total protein, AST, and ALT, and lower mean values of calcium and potassium, exceeding acceptable biases. Notably, inorganic phosphate showed the largest % bias (51.14%). In the PEG–ELSs laxative group, higher mean values of inorganic phosphorus, creatinine, uric acid, AST, and total bilirubin and a lower mean value of potassium were observed compared with controls, exceeding acceptable biases. The effects of NaPs on inorganic phosphate, calcium, and electrolyte levels exceeded those of PEG–ELSs.

Conclusions

PEG–ELSs rather than NaPs are recommended as the first choice for bowel preparation, taking safety concerns and the reliability of laboratory values into account. Blood chemistry data from blood samples drawn after the ingestion of laxatives for colonoscopy should be interpreted with caution.     

Massive Ethylene Glycol Poisoning Triggers Osmotic Demyelination Syndrome

Background

Ethylene glycol is a toxic organic solvent implicated in thousands of accidental and intentional poisonings each year. Osmotic demyelination syndrome (ODS) is traditionally known as a complication of the rapid correction of hyponatremia.

Objective

Our aim was to describe how patients with ethylene glycol toxicity may be at risk for developing ODS in the absence of hyponatremia.

Case Report

A 64-year old female patient was comatose upon presentation and laboratory results revealed an anion gap of 39, a plasma sodium of 150 mEq/L, a plasma potassium of 3.5 mEq/L, an osmolal gap of 218, an arterial blood gas pH of 7.02, whole blood lactate of 32 mEq/L, no measurable blood ethanol, and a plasma ethylene glycol concentration of 1055.5 mg/dL. The patient was treated for ethylene glycol poisoning with fomepizole and hemodialysis. Despite having elevated serum sodium levels, the patient's hospital course was complicated by ODS.

Conclusions

Rapid changes in serum osmolality from ethylene glycol toxicity or its subsequent treatment can cause ODS independent of serum sodium levels.     

Physiology of the salivary glands

Salivary gland products are essential for oral health. Saliva is produced by three pairs of major salivary glands, the parotid, the submandibular and sublingual glands and by numerous minor salivary glands scattered around the oral cavity. Salivary water and electrolyte secretion is an energy consuming active two-stage process. First the acini secrete isotonic primary saliva into the luminal terminal end pieces of the gland parenchyma. This saliva is then modified by electrolyte reabsorption to form a hypotonic secretion in the ductal systems. Salivary proteins are continuously synthesized, and stored in secretory granules within the cell. Both electrolyte and protein secretion are highly regulated processes. Electrolyte secretion is primarily stimulated by parasympathetic stimulation while protein secretion is preferentially activated by sympathetic stimulation, but there is a considerable cross-talk and synergism between the two regulatory pathways. Approximately 1.0–1.5 litres of saliva is secreted by healthy persons each day, consisting of water, electrolytes, lubricants, antimicrobial compounds, enzymes and growth factors. These components of saliva facilitate speech, mastication and swallowing, and initiate food digestion. In addition, it protects the oral mucosa and the teeth. Thus, saliva secreted into the oral cavity is essential to maintain physiological conditions in the mouth.