Hydropneumatic anal dilation in conservative treatment of chronic anal fissure: clinical outcomes and randomized comparison with topical nitroglycerin

Abstract. Background The surgical approach in chronic anal fissures (CAF) may, occasionally result in anal incontinence. The aim of this investigation was to study feasibility, effectiveness, and safety of hydropneumatic anal dilation (HAD) in conservative treatment of CAF and to compare it with local nitroglycerin (GTN) treatment.Methods Efficacy of HAD was evaluated in 109 patients (65 male, 44 female; mean age, 53.3 years), following anal dilation using Microvasive Rigiflex instrument (Otw 40 mm). Thereafter, 36 patients were randomly divided into two groups to undergo treatment with 0.25% GTN or HAD.Results Recovery rate with HAD was 79.8% after 10 days and 94.5% after 30 days. An immediate (within 24 hours) drop was observed in the level of pain; no significant complications or recurrence were reported within 2 years. Healing rate was 94.5% following HAD vs. 38.9% after GTN.Conclusion HAD should be considered a new safe option in CAF treatment.     

Activation of trigeminovascular neurons by glyceryl trinitrate

The effect of intra-carotid arterial infusions of glyceryl trinitrate (GTN), a substance known to precipitate headache, including migraine, upon the spontaneous activity of trigeminal neurons with craniovascular input was studied in cats. Second-order craniovascular neurons which received sensory input from the superior sagittal sinus were recorded in the trigeminal nucleus caudalis. Infusions of GTN were administered via a catheter inserted retrogradely into the common carotid artery through the lingual artery. Infusions of GTN (100 microg kg(-1) min(-1) in a volume of 2 ml min(-1)) increased the mean basal discharge rate of all second-order neurons to 239+/-47% of control. GTN produced a fall in mean blood pressure, but there was no correlation between this fall and the changes in discharge rate. GTN infusions sensitised neurons to the effects of electrical stimulation of the superior sagittal sinus, but not to subsequent GTN infusions. Infusions of similar volumes of vehicle did not alter the discharge rate of neurons. We conclude that GTN activates craniovascular sensory pathways at a site at, or peripheral to, the second-order neuron and that such an action may account for at least the acute-onset headache induced by GTN.     

Local application of EMLA and glyceryl trinitrate ointment before venepuncture

One hundred unpremedicated fit day surgery patients aged between 27 and 68 years were allocated randomly into one of four groups and EMLA, glyceryl trinitrate, EMLA and glyceryl trinitrate or a placebo ointment was applied to the dorsum of a hand. The pain and ease of venepuncture were determined at induction of anaesthesia 60 minutes later. Pain scores were also reassessed 1-2 hours after operation. Lower pain scores and easier venepuncture occurred when EMLA and glyceryl trinitrate ointment was applied to the dorsum of the hand.     

硝酸甘油介入~(99m)Tc-MIBI心肌显像定量测定心肌梗死面积及心肌存活的实验研究

目的　为了比较犬心肌梗死 (MI)模型的静息心肌显像、潘生丁介入心肌显像、硝酸甘油 (NTG)介入心肌显像所测定MI面积及存活心肌与病理性MI面积。方法　选择 12条杂种犬建立MI模型 ,给予NTG1.0mg后行心肌显像。次日将犬随机分为两组 :一组进行常规静息显像 ,另一组进行潘生丁介入显像 ,采用靶心图测定MI面积 ,并与病理性MI面积进行对比研究。结果　犬病理性MI面积为 ( 17.80± 3 .0 7) % ,NTG介入显像、静息显像、潘生丁介入显像测定MI面积分别为 ( 19.98± 3 .16 ) %、( 2 5 .5 3± 3 .91) %、( 31.82± 2 .82 ) %。其中NTG介入显像测定MI面积与病理性MI面积大小最为接近 (P >0 .0 5 ) ,并有很好相关性 (r =0 .91)。静息显像有 ( 2 1.5 2± 4.8) %、潘生丁显像有 ( 37.80± 4.5 ) %的梗死心肌在使用NTG后得到恢复。结论　利用NTG介入显像后可以降低静息显像、潘生丁介入显像所测得的MI面积与实际MI面积的误差 ,并可提高两者存活心肌的检出率。     

~(99m)Tc-MIBI心肌显像心肌活力评估及在冠脉成形术中的应用研究

目的　探讨有效提高常规静息９９ｍＴｃ－甲基异丁基异腈（ＭＩＢＩ）心肌显像检测存活心肌的方法,评价该方法在血管成形术中评估存活心肌的价值。方法分别对２０例、３０例和１０例冠心病病人血管成型术前和术后进行,（１）静息－含服硝酸甘油介入,（２）静息－门控,（３）静息－延迟（４ｈ）９９ｍＴｃ－ＭＩＢＩ心肌显像。结果 ３种方法评估存活心肌阳性预测值分别为９５．９％、６８．５％和８４．１％;阴性预测值分别为６８．２％、９０．１％和９０．０％;预测准确率分别为８２．５％、７７．３％和８７．２％。结论（１）～（３）种显像方法有效地提高了常规静息９９ｍＴｃ－ＭＩＢＩ心肌显像为血管成形术适应证的选择和临床评估其疗效提供了客观依据。     

三叉神经痛大鼠三叉神经节内谷氨酸表达分布的研究

目的研究三叉神经痛(TN)大鼠时其三叉神经节(TG)内谷氨酸(Glu)表达与分布的关系。方法皮下注射硝酸甘油构建三叉神经痛大鼠模型;应用免疫组化技术检测大鼠三叉神经节Glu含量与分布。结果皮下注射硝酸甘油构建三叉神经痛大鼠的三叉神经节内Glu含量增多且其主要分布在三叉神经节表层。结论 Glu可能与三叉神经痛发生有密切关系。     

A systematic review of medical therapy for anal fissure

PURPOSE This is a meta-analysis of randomized, controlled trials to assess the efficacy and morbidity of medical therapies for anal fissure.METHODS Medline and the Cochrane Controlled Trials Register and the Cochrane Colorectal Cancer Review Groups Controlled Trials Register were searched using the terms anal fissure randomized from 1966 to 2002. Studies in which participants were randomized to a nonsurgical therapy for anal fissure were the focus of this review. Comparison groups included an operative procedure, an alternate medical therapy, or placebo. Chronic fissure, acute fissure, and fissure in children were included in the review, however, atypical fissure associated with inflammatory bowel disease, cancer, or anal infection were excluded. Data were abstracted from published reports and meeting abstracts, assessing method of randomization, blinding, intention to treat and dropouts, therapies, supportive measures, dosing and frequency, and crossovers. Outcome measures included nonhealing of the fissure and adverse events.RESULTS Twenty one different comparisons of medical therapies to heal anal fissure have been reported in 31 trials, including 9 agents—glyceryl trinitrate, isosorbide dinitrate, botulinum toxin, diltiazem, nifedipine, hydrocortisone, lidocaine, bran, placebo—as well as anal dilators and surgical sphincterotomy. Glyceryl trinitrate was favored in the analysis over placebo (odds ratio = 0.55, 95 percent confidence interval, 0.41–0.74). After excluding two studies from analysis because of placebo response rates >2 standard deviations below the mean for all studies, the advantage of glyceryl trinitrate over placebo was no longer statistically significant (odds ratio = 0.78; 95 percent confidence interval, 0.56–1.08). Nifedipine and diltiazem did not differ from glyceryl trinitrate in their ability to cure fissure (0.66; 0.22–2.01). Botulinum toxin compared with placebo showed no significant efficacy (0.75; 0.32–1.77), and was also no better than glyceryl trinitrate (0.48; 0.21–1.10). Surgery was more effective than medical therapy in curing fissure (0.12; 0.07–0.22).CONCLUSIONS Medical therapy for chronic anal fissure, acute fissure, and fissure in children may be applied with a chance of cure that is only marginally better than placebo, and for chronic fissure, far less effective than surgery.Reprints are not available.     

Clinical pharmacokinetics of nitrates

Summary The pharmacokinetics of organic nitrates are discussed with emphasis on the possible clinical relevance. For glyceryl trinitrate, the measurement of plasma concentrations is very difficult. Its pharmacokinetics are unusual, with a very rapid disappearance from plasma, and large intraindividual and interindividual variations. After oral administration, there seems to be a very extensive first-pass hepatic extraction and the plasma concentrations are often below the detection limit; after sublingual administration, glyceryl trinitrate appears in plasma. With transdermal glyceryl trinitrate controlled-release systems, plasma concentrations of glyceryl trinitrate can be maintained over 24 hours, although with fluctuations and important intraindividual and interindividual variability. After administration of glyceryl trinitrate via different routes, glyceryl dinitrates and mononitrates are present in plasma. The pharmacokinetics of isosorbide dinitrate are somewhat easier to understand. The substance disappears less rapidly from the plasma than does glyceryl trinitrate. After oral administration, there is also a hepatic first-pass extraction; the plasma concentrations can be prolonged by administering slow-release products. Sublingual administration leads to higher plasma concentrations than oral administration. Isosorbide dinitrate is metabolized in the organism to isosorbide 5-mononitrate and isosorbide 2-mononitrate, which both have vasodilator activity: after administration of isosorbide dinitrate, the mononitrates, and mainly the 5-mononitrate, reach very high concentrations in plasma. Isosorbide 5-mononitrate has been studied in its own right as an antianginal agent: it is completely absorbed after oral administration; it has a half-life of around 4 hours, and oral standard and controlled-release formulations have been extensively studied. For several reasons, including attenuation of the effects with time and the appearance of active metabolites, the relationship between the plasma concentrations of nitrates and their therapeutic effects is very complex. Knowledge of the pharmacokinetics of these substances is only of limited interest.     

Enhanced Preservation of Pig Cardiac Allografts by Combining Erythropoietin With Glyceryl Trinitrate and Zoniporide

Erythropoietin has a tissue‐protective effect independent of its erythropoietic effect that may be enhanced by combining it with the nitric oxide donor glyceryl trinitrate (GTN) and the sodium–hydrogen exchange inhibitor zoniporide in rat hearts stored with an extracellular‐based preservation solution (EBPS). We thus sought to test this combination of agents in a porcine model of orthotopic heart transplantation incorporating donor brain death and total ischaemic time of approximately 260 min. Pig hearts were stored in one of four storage solutions: unmodified EBPS (CON), EBPS supplemented with GTN and zoniporide (GZ), EBPS supplemented with erythropoietin and zoniporide (EZ), or EBPS supplemented with all three agents (EGZ). A total of 4/5 EGZ hearts were successfully weaned from cardiopulmonary bypass compared with only 2/5 GZ hearts, 0/5 CON hearts and 0/5 EG hearts (p = 0.017). Following weaning from bypass EGZ hearts demonstrated superior contractility and haemodynamics than GZ hearts. All weaned hearts displayed impaired diastolic function. Release of troponin I from EGZ hearts was lower than all other groups. In conclusion, supplementation of EBPS with erythropoietin, glyceryl trinitrate and zoniporide provided superior donor heart preservation than all other strategies tested.     

大鼠静脉注射硝酸甘油后脑膜ICAM-1表达的研究

目的:观察大鼠偏头痛不同时相脑膜组织细胞间黏附因子1(ICAM-1)的表达特征.方法:采用硝酸甘油(GrN)2 μg/kg·min-1iv法建立大鼠偏头痛模型,采用Western blot法观察对照组、GTNiv0.5,2,4,6,10 h组脑膜中的ICAM-1蛋白表达量.结果:GTN iv后4 h大鼠脑膜ICAM-1蛋白表达量增高,6 h蛋白表达量达高峰,然后逐渐回落,至10 h接近正常水平.结论:GTN iv呈时限性ICAM-1蛋白表达增强,提示ICAM-1参与了偏头痛的病理过程.