Multicenter Randomized Study on the Efficacy of Isosorbide in Patients with Mèniére's Disease / 대한평형의학회지

OBJECTIVES: Mèniére's disease is one of the most common causes of episodic vestibular syndrome that shows symptom complexes of recurrent vertigo, hearing loss, tinnitus and ear fullness. Isosorbide (Isobide) is a osmotic diuretics which has been used for Meniere's disease to reduce the endolymphatic pressure. The purpose of this study was to evaluate the efficacy of isosorbide in the treatment of Mèniére's disease by comparing the combined therapy of isosorbide and betahistine (Meniace) to betahistine only. METHODS: Among 220 patients enrolled with Mèniére's disease from 9 centers, 187 patients completed this clinical study. Patients were randomly subjected either to betahistine alone therapy at dose of 6 mg three times a day (n=97) or to combined therapy with isosorbide (dose of 30 mL three times a day) and betahistine (n=90) for 12 weeks. Two groups were compared at 4 and 12 weeks after treatment on frequency of vertigo, hearing level (pure tone audiometry, speech audiometry), electocochleography (ECoG), tinnitus (Tinnitus Handicap Inventory, THI) and quality of life (Korean functional level scale, Korean dizziness handicap inventory). RESULTS: During first 4 weeks after treatment, the frequency of vertigo was not reduced in either betahistine alone therapy group or combined therapy group. However, between 8 and 12 weeks, the frequency of vertigo was significantly reduced in either group, and in the combined group frequency of vertigo was more significantly reduced than in the betahistine alone therapy group (p=0.041). The hearing level, ECoG, tinnitus and quality of life was not significantly different between two groups. CONCLUSION: Isosorbide and betahistine combined therapy were more effective for vertigo control than betahistine alone therapy. Isosorbide is an effective diuretic in vertigo control in definite Mèniére's disease.

Isosorbide Concentration in Perilymph of the Guinea Pig After Oral Administration Versus That After Round Window Perfusion

OBJECTIVES: The aims of this study were to investigate the feasibility of isosorbide delivery into perilymph through the round window membrane (RWM), and to compare the intracochlear isosorbide concentration in perilymph after oral administration (PO) versus that after round window perfusion (RWP). METHODS: Sixteen male guinea pigs (32 ears) were used. Isosorbide, an osmotic diuretic, was administered via RWP or PO. First, to investigate the optimal perfusion time, perilymph sampling of scala tympani from the RWM was performed after RWP for 15, 30, or 60 minutes. Second, to compare the drug concentration after RWP versus that after PO, perilymph was aspirated at 3 and 6 hours after administration. Intracochlear concentration of isosorbide was analyzed by high-performance liquid chromatography coupled to refractive index detection. RESULTS: Isosorbide passed through the RWM into perilymph after RWP. After RWP for 15, 30, and 60 minutes, mean isosorbide concentrations in perilymph were 116.27+/-44.65, 245.48+/-112.84, and 279.78+/-186.32 mM, respectively. The intracochlear concentration after RWP for 30 minutes was higher than that after RWP for 15 minutes (P=0.043). At 3 and 6 hours after PO, isosorbide concentrations in perilymph were 28.88+/-4.69 and 12.67+/-2.28 mM, respectively. In contrast, the corresponding concentrations after RWP were 117.91+/-17.70 and 75.03+/-14.82 mM at 3 and 6 hours, respectively. Isosorbide concentrations in perilymph following RWP were significantly higher than those following PO at both 3 and 6 hours (P=0.025 and P=0.034, respectively). CONCLUSION: Isosorbide can rapidly pass through the RWM after RWP in guinea pigs, and 30 minutes of perfusion is considered to be appropriate. In addition, over a 6-hour period, RWP can deliver higher concentrations of isosorbide into perilymph than those achieved with PO.

Avaliação do tratamento de fissura anal crônica com isossorbida tópica a 1 por cento / Evaluation of the treatment of chronic anal fissure with topical isosorbide 1 percent

INTRODUÇÃO: Fissuras anais crônicas são úlceras benignas, dolorosas, profundas. Ocorrem devido a trauma das fezes, hipertonia esfincteriana e pobre vascularização. Cirurgia é mais efetiva, porém com efeitos adversos (incontinência anal). Terapia conservadora consegue decréscimo transitório da pressão de repouso, cicatrizando muitas lesões, sem dano muscular. MÉTODOS: Objetivando avaliar tratamento de fissuras crônicas com isossorbida (ISO) a 1 por cento tópica, foi realizado um ensaio clínico, duplo-cego em pacientes do Serviço de Coloproctologia da Universidade Federal de Sergipe (UFS) - Aracaju, Sergipe, durante um ano. Foram estudados 24 pacientes: 14 no Grupo 1 - creme com ISO, e 10 no Grupo 2 - placebo. Avaliaram-se comportamento da pressão de repouso, melhora da dor e grau de cicatrização das feridas com e sem ISO. RESULTADOS: Resultados mostraram que a fissura acometeu mais mulheres, a constipação foi observada em 58,3 por cento. Quanto à dor, obteve-se menor intensidade no Grupo 2, mas sem significância. A cicatrização ao fim de 60 dias foi igual nos dois grupos (50 por cento). Quanto às médias de pressão de repouso com 30 e 60 dias, houve queda no padrão em ambos os grupos, porém sem significância. Observou-se que pacientes curados foram os de maior redução de pressão de repouso. CONCLUSÃO: Concluiu-se que a ISO não modificou o padrão de resposta manométrica; todavia, houve melhora clínica importante nos dois grupos, cuja taxa de cicatrização foi equivalente.

INTRODUCTION: Chronic anal fissures are deep, benign and painful ulcers. The involved factors are local trauma, sphinter hypertonia and poor blood flow. Surgery is gold standard treatment, but it causes fecal incontinence. Medical non-surgical therapy gets transitory resting pressure reduction and cure of lesions, without muscular damage. METHODS: In order to evaluate the treatment of chronic anal fissures using topical isossorbide (ISO) 1 percent, a randomizated and double-blind study twas carried out in Coloproctology Section of Universidade Federal de Sergipe (UFS), Sergipe, Brazil, during one year. Twenty-four patients were evaluated: 14 in Group 1 - ISO cream, and 10 in Group 2 - placebo. Resting pressure profile, improvement of painful symptoms and degree of scaring of the fissure were evaluated. RESULTS: Ulcer was more prevalent in women, constipation was present in 58.3 percent. The evacuatory pain was less common in Group 2, but without statistical significance. After 60 days, the healing was equal in the both groups (50 percent). There was a small reduction of resting pressure means at the end of 30 and 60 days, without statistical significance. Healing patients presented more resting pressure reducing. CONCLUSION: ISO cream did not influence the manometric response standard; otherwise it offered clinical improvement in both groups, whose scarring index was similar.

Propranolol, isosorbide mononitrate and endoscopic band ligation - alone or in varying combinations for the prevention of esophageal variceal rebleeding

To compare the efficacy of propranolol, propranolol with nitrate, band ligation, and band ligation with propranolol and nitrate for the prevention of esophageal variceal rebleeding. A prospective randomized trial. Department of Gastroenterology and Hepatology, Sheikh Zayed Hospital, Lahore, from November 2003 to July 2005. One hundred and sixty cirrhotic patients with esophageal variceal bleeding were randomized to four treatment groups [propranolol, propranolol plus isosorbide mononitrate, band ligation, band ligation plus propranolol and nitrate] with 40 patients in each group. Patients were followed for 6 months after the enrolment of last patient. Primary end points were recurrence of esophageal variceal bleeding and death. Treatment complications were noted. Four treatment groups were comparable regarding baseline characteristics. Esophageal variceal rebleeding occurred in 22% patients in band ligation plus drugs group, 26% patients in drug combination group, 31% patients in banding group and 38% patients in propranolol group [p=0.41]. Difference in mortality rates was also not significant. There was no significant difference between treatment groups in prevention of esophageal variceal rebleeding

Effect of prophylactic continuous infusion of isosorbide dinitrate on myocardial protection and hemodynamics in patients undergoing off-pump coronary bypass surgery

BACKGROUND: Multi-vessel off-pump coronary bypass surgery (OPCAB) imposes cumulative myocardial ischemia/reperfusion injury, which may be attenuated by continuous infusion of nitrate. However, nitrate infusion and consequent decrease in preload may be hazardous during heart displacement which causes restrictive filling of the ventricles. Therefore, we evaluated the effect of nitrate infusion on myocardial protection and hemodynamics in patients undergoing OPCAB, in a prospective, randomized and controlled trial. METHODS: Fifty patients with stable angina and left ventricular ejection fraction >40% undergoing elective, isolated, multivessel OPCAB were enrolled. Patients were randomized equally to either continuous infusion of isosorbide dinitrate 0.5microg/kg/min or same amount of normal saline during the surgery. Operative data including hemodynamic variables, intraoperative ST segment changes and postoperative cardiac enzyme release (creatine kinase-MB, troponin T) were compared. RESULTS: Patients characteristic and operative data including ST segment changes and use of vasopressors were similar between the groups except the total amount of infused crystalloid during the surgery which was significantly higher in the nitrate group. Postoperative variables including cardiac enzyme release were also similar between the groups. CONCLUSIONS: Prophylactic continuous infusion of nitrate during OPCAB exerted no additional benefit in terms of myocardial protection. It also, was not associated with accentuated decrease in cardiac output during heart displacement, and the decrease in preload seems to have been nullified by modest increase in fluid therapy.

The Effect of Isosorbide Dinitrate Intravenous Injection on the Hemodynamics and Arterial Stiffness of Patients with Isolated Systolic Hypertension

BACKGROUND AND OBJECTIVES: In clinical practice, isolated systolic hypertension (ISH) is common for elderly patients and it is correlated with cardiovascular mortality. However, it is difficult to control the systolic blood pressure (BP) with using the currently available antihypertensive drugs without influencing the diastolic BP. The purpose of this study is to evaluate the effect of isosorbide dinitrate on the central BP and arterial stiffness by performing invasive testing. SUBJECTS AND METHODS: Thirty subjects who had ISH and who underwent coronary angiography were enrolled in this study. The invasively measured central blood pressure, pulse pressure and pulse wave velocity were obtained after isosorbide dinitrate was injected intravenously and these values were analyzed in relation to age, gender, the body mass index, diabetes mellitus, dyslipidemia, smoking and the current dosing with antihypertensive drugs. RESULTS: One minute after intravenous injection of isosorbide dinitrate, the central systolic BP was significantly decreased compare to the baseline value (142.23+/-12.32 mmHg vs 164.97+/-14.43 mmHg, respectively, p<0.001), and this change was sustained for 5 minutes (141.05+/-14.84 mmHg vs 164.97+/-14.43 mmHg, respectively, p<0.001). The mean values, during the 5 minute period, of the pulse pressure (65.99+/-13.63 mmHg vs 87.30+/-13.71 mmHg, respectively, p<0.001) and the pulse wave velocity (11.22+/-3.20 m/sec vs 12.91+/-4.11 m/sec, respectively, p<0.001) also revealed significant changes. Yet there was no significant decrease of the diastolic BP. Analysis of subgroups that were classified by gender, age, BMI, diabetes mellitus, dyslipidemia, smoking, the degree of the systolic BP and PWV, and taking antihypertensive drugs showed a similar pattern. CONCLUSION: Isosorbide dinitrate was very effective for selective control of the systolic BP in ISH patients. It is also expected to prevent cardiovascular complications by improving arterial stiffness.

Utilidad de isosorbide sublingual en la reversibilidad de la hipertensión pulmonar reactiva, en pacientes candidatos a trasplante cardíaco / Usefulness of sublingual isosorbide to assess the reversibility of pulmonary hypertension in cardiac transplant candidates

Background: Continuous infusion of short life vasodilators are employed to test reversibility of pulmonary hypertension in cardiac transplant candidates. Sublingual isosorbide administration has not been described in the literature and it might be a simpler alternative. Aim: To evaluate sublingual isosorbide administration as a test of reversibility of pulmonary hypertension in heart failure. Patients and Methods: Prospective evaluation of patients referred for cardiac transplant evaluation. Patients underwent right catheterization for hemodynamic measurements at baseline and after repeated doses of 5 mg sublingual isosorbide every 5 minutes until observing a decrease in pulmonary vascular resistance decrease or symptomatic hypotension. Results: Twenty one patients, 18 men, age 49±15 years, were studied. Fourteen (66%) were transplanted. The mean sublingual isosorbide dose was 15±5 mg. After isosorbide administration, there was a significant decrease in mean arterial pressure (80±8.5 to 71±6.6 mmHg, p <0.0001), mean pulmonary artery pressure (38±11 to 26±7.8 mmHg, p <0.0001), systemic vascular resistance (1540±376 to 1277±332 dyn*s/cm5 p <0.001), pulmonary vascular resistance (3.5±2.2 to 2,5±1.6 Wood Units, p <0.05) and transpulmonary gradient (13±7 a 10±4 mmHg, p <0.004). The cardiac output increased from 3.96±0.7 to 4.38±0.9 L/min, p=0.05. The relation between pulmonary and systemic vascular resistance before and after isosorbide was 0.17 and 0.15, respectively (p=0.04). One transplanted patient with partial reversibility of pulmonary hypertension developed acute right heart failure. Conclusions: Sublingual isosorbide administration is useful and well tolerated to evaluate the reversibility of pulmonary hypertension prior cardiac transplant.

comparison of isosorbide mononitrate, misoprostol and combination therapy for preinduction cervical ripening at term: a randomized controlled trial

The purpose of this study was to compare the efficacy, safety, and acceptability of isosorbide mononitrate [IMN], misoprostol, and the combination therapy for cervical ripening before induction of labor at term. A prospective, double-blind, placebo-controlled, randomized clinical trial in 196 term and post-term nulliparous women with unfavorable cervices who were assigned randomly to receive either 40mg of IMN [n=65], 50 micro g of misoprostol [n=65], or both of them [n=66] in the posterior vaginal fornix. Changes in Bishop score and cervical length, progress and outcomes of labor and adverse effects were assessed. The combination therapy was more effective than IMN or misoprostol. Successful induction [vaginal delivery within 24 h of initiation of cervical ripening] was significantly higher in the misoprostol [60%] and combination therapy [62.1%] groups compared with the IMN [27.7%] group [P<0.0001]. Mean duration [h] from treatment initiation to delivery was greater for IMN [26.7 +/- 7.5] than misoprostol [16.5 +/- 6.7] and combination therapy [14.8+6.2] groups [P<0.0001]. Oxytocin was needed more in the IMN group [93.8%] than in the misoprostol [21.5%] and combination therapy [25.8%] groups [P<0.0001]. IMN was safer and more acceptable than misoprostol and combination therapy. The cesarean rate was not significantly different among groups, but the major indications were different: dystocia [54.5%] in the IMN group versus persistent non-reassuring FHR pattern [57.9%] in the misoprostol and [47.6%] in the combination therapy groups [P=0.01]. The combination therapy was more effective than either IMN or misoprostol alone for preinduction cervical ripening at term. However, IMN was safer, well tolerated and more acceptable

Prevention of Variceal Bleeding and Measurement of Hepatic Vein Pressure Gradient / 대한간학회지

No abstract available.

Estudo comparativo do uso do diltiazem como droga antiespástica em cinecoronariografia por via transradial / Comparative study of the use of diltiazem as an antispasmodic drug in coronary angiography via the transradial approach

OBJECTIVE: To evaluate the impact of the use, prior to the procedure, of injectable diltiazem to prevent complications. METHODS: Between September 2000 and July 2001, 50 patients underwent transradial coronary angiography and were randomized to receive placebo (GI) or diltiazem (GII) through a catheter inserted into the radial artery. All patients received isosorbide mononitrate. Ultrasound analyses of the radial artery were performed before examination, 30 minutes afterwards, and 7 days afterwards to evaluate the flow, the diameter, and the artery output. RESULTS: The radial artery diameter of GI was 2.4± 0.5 mm before the procedure and 2.3±0.5 mm after 30 minutes (NS), whereas in GII the diameter was 2.2±0.3 mm before the examination and 2.5±0.4 mm 30 minutes after it (P<0.001). Radial artery output in group 1 was 7.3±5.l2 mL/min before the examination and 6.1±3.5 mL/min 30 minutes after the examination (NS), and GII had an increase of 5.9±2.5 mL/min before examination to 9.05± 7.78 mL/min after the examination (P=0.04). Complications (spasm, occlusion, and partial obstruction) occurred in 4 patients (17.4 percent) in GI and did not occur in GII (P=0.04). CONCLUSION: The study suggests a decrease in vascular complications through the transradial access for coronary angiography with the use of diltiazem as an antispasmodic drug, resulting in the significant increase in the diameter of the radial artery and radial artery output

Effect of aqueous garlic [Allium sativum L.] extract on acetylcholine and isosorbide-induced relaxation of isolated aorta in rat

The hypotensive effect of garlic has been well-documented in human subjects and animals. Since endothelial activity regulates vascular reactivity in physiological and pathophysiological conditions, the aim of the present study was to investigate the effect of garlic on endothelium-dependent and independent relaxation of rat aorta for elucidation of mechanism of the garlic anti-hypertensive effect. Four and eight weeks after treatment with garlic extract, aortic rings were studied for relaxation response to acetylcholine and isosorbide dinitrate. The obtained results showed that endothelium-dependent relaxation response of aortic rings to acetylcholine, from rats treated with garlic for 4 and 8 weeks, increases about 5-24% and 3-27%, respectively compared to controls. But, endothelium-independent relaxation response to isosorbide showed no difference in all groups. Moreover, the relaxant effect of garlic extract was time-dependent. The obtained findings strongly suggest that garlic exerts its relaxant effect through endothelium by production and/or releasing of endothelium-derived relaxing factor

A Ratio of Arterial Oxygen Tension to Inspired Oxygen Fraction (PaO2/FiO2 ratio) after Cardiopulmonary Bypass in Coronary Artery Bypass Graft Surgery: Amrinone-Dopamine versus Isosorbide Dinitrate-Dopamine / 대한마취과학회지

BACKGROUND: Cardiopulmonary bypass (CPB) may produce lung injury with decreased PaO2/FiO2 ratio in patients undergoing CABG surgery. We examined PaO2/FiO2 ratio and incidence of PaO2/FiO2 < 300 or 150 to determine the differences in oxygenation with the use of amrinone-dopamine (DP) or isosorbide dinitrate (IDN)-DP in patients undergoing CABG. METHODS: Twenty patients undergoing elective CABG were divided into two groups according to drug used on separation from CPB: IDN-DP (Group 1, n = 10) or amrinone-DP (Group 2, n = 10). Anesthesia was induced and maintained with propofol, fentanyl and vecuronium. IDN infusion (1.0microgram/kg/min) was started preoperatively in both groups. Mild hypothermic CPB was applied with a roller pump and nonpulsatile flow maintained a mean arterial pressure of 60-80 mmHg. In Group 2, amrinone was administered (0.75 mg/kg + 10microgram/kg/min) instead of IDN at the time of CPB separation. DP infusion (3microgram/kg/min) was started at a rectal temperature more than 35.5oC and adjusted to maintain acceptable hemodynamics. IDN-DP or amrinone-DP infusion, monitoring and sedation with propofol were continued in the intensive care unit (ICU). PaO2/FiO2 ratio under controlled ventilation with air/O2 mixture (FiO2 0.6) was checked immediately before CPB (pre-CPB), 30 mins (post-CPB30), 60 mins after CPB (post-CPB60) and 30 mins after admission to ICU (ICU30). RESULTS: There was no significant difference between the groups in the terms of the duration of arotic cross clamp, PaO2/FiO2 at pre-CPB, PaO2/FiO2 at post-CPB60, PaO2/FiO2 at ICU30 or in the incidence of PaO2/FiO2 < 150, PaO2/FiO2 < 300 at ICU30. But there was a significant difference in PaO2/FiO2 post CPB30 (263.3 +/- 105.5 in Group 1 vs. 381.7 +/- 69.5 in Group 2, P<0.05). CONCLUSIONS: Amrinone-DP provides more favorable oxygenation immediately after CPB in CABG surgery than IDN-DP.

Crisis de esclerodermia renal: rol de la vasculopatía esclerodérmica en la inducción de fibrosis cutáneo-visceral en dos casos / Renal scleroderma crisis: role of sclerodermic vasculopathy in the induction of cutaneous and visceral fibrosis: report of 2 cases

Although fibrosis and vasculopathy coexist in most patients with progressive systemic sclerosis, it is not clear if these events are the result of an unique etiologic factor or if one is consequence of the other. We report two cases of progressive systemic sclerosis that evolved to a renal scleroderma crisis. A 36 years old female presented with a Sjögren syndrome and painful subcutaneous nodules whose biopsy showed perivascular lymphocytic infiltration, perivascular thickening and normal skin. The ESR was 100 mm/h. She developed an hypertensive crisis and progressive renal failure, followed by a rapidly evolving progressive systemic sclerosis. The patient died in the course of this crisis. A 32 years old female with a progressive systemic sclerosis refractory to D-penicillamine treatment, receiving cyclosporin, presented a renal scleroderma crisis, that was successfully treated, with complete recovery of renal function. We highlight the different evolution of these cases, probably due to an early diagnosis and a better experience in the management of this condition

A Case of Myocardial Infarction caused by a Variant Angina during Treatment with beta-blocker of Intramural Hematoma

Variant angina is characterized by repeated attack at rest associated with ST-segment elevation on ECG and caused by the spasm of coronary artery. But, the pathogenesis of spasm is not well known. A 44-year old man was transferred for the management of intramural hematoma at descending thoracic aorta and uncontrolled hypertension. We started to control hypertension with nitroprusside, propranolol, amlodipine, and doxazocin. At 4th hospital day, severe chest pain, dizziness, and diaphoresis were developed, and ECG showed not only ST-segment elevation on lead II, III, aVF but also 2 degree AV block(Mobitz type II). CK-MB revealed 52.3 ng/dl. When coronary angiography performed emergently, it showed total occlusion of right coronary artery (RCA) and diffuse minimal narrowing of left anterior descending coronary artery (LAD). After nitroglycerin was infused via right coronary catheter, the RCA was opened completely, and reperfusion arrhythmia was developed. Medication were changed to nifedipine, diltiazem, nicorandil, isosorbide mononitrate and he had no more chest pain.

Eficacia del isosorbide en aerosol en el manejo de la crisis hipertensiva de la preeclampsia severa / Efficancy of isosorbide in aerosol in the management of hypertensive crisis of severe preeclampsia

En un estudio clínico aleatorizado se evaluaron 36 pacientes con preclampsia severa divididos en dos grupos de 18 pacientes c/u. Grupo A: Recibieron 1.25 mg de isosorbide en aerosol oral al ingreso, repitiéndose la dosis a los 10 minutos si la reducción en la presión arterial media fue < 15 por ciento, Grupo B: Recibieron sulfato de magnesio en infusión continua intravenosa, 4 g la primera hora y después un gramo por hora durante cinco horas. En ambos grupos se administró terapia con líquidos parenterales y se vigiló con monitor la presión arterial desde el ingreso, se determinó frecuencia cardiaca materna (FCM), fetal (FCF) y proteinuria antes y después del fármaco, así como el Apgar del producto al minuto y a los cinco minutos. El grupo A presentó disminución significativa de la presión arterial (p<0.0002), FCM (p<0.005), FCF (p<0.05), 13 pacientes con una aplicación y cinco con dos. En el grupo B tres pacientes no respondieron, y el resto tuvo un mal control de la presión arterial (p>0.05), sin cambios en FCM. FCM y proteinuria. En ningún caso hubo progresión a eclampsia. Al comparar ambos grupos entre sí, hubo una diferencia significativa para la presión arterial (<0.005), FCM (p<0.05), FCF (p<0.002) y Apgar al minuto (p<0.01) en el grupo con isosorbide. Los datos sugieren que el isosorbide es eficaz y seguro en el manejo de la preeclampsia severa

A Case of Endoscopic Removal of Common Bile Duct Stone with Isosorbide Dinitrate / 대한소화관운동학회지

No abstract available.