Comparison of the apoptotic effects of topically applied papaverine, diltiazem, and nitroprusside to internal thoracic artery

Abstract Objective: To detect and to compare the apoptotic effects of intraoperatively topically applied diltiazem, papaverine, and nitroprusside. Methods: Internal thoracic artery segments of ten patients were obtained during coronary bypass grafting surgery. Each internal thoracic artery segment was divided into four pieces and immersed into four different solutions containing separately saline (Group S), diltiazem (Group D), papaverine (Group P), and nitroprusside (Group N). Each segment was examined with both hematoxylin-eosin and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method in order to determine and quantify apoptosis. Results: Apoptotic cells were counted in 50 microscopic areas of each segment. No significant difference was observed among the four groups according to hematoxylin-eosin staining. However, the TUNEL method revealed a significant increase in mean apoptotic cells in the diltiazem group when compared with the other three groups (Group S=4.25±1.4; Group D=13.31±2.8; Group N=9.48±2.09; Group P=10.75±2.37). The differences between groups were significant (P=0.0001). No difference was observed between the samples of the diabetic and non-diabetic patients in any of the study groups. Conclusion: The benefit of topically applied vasodilator drugs must outweigh the potential adverse effects. In terms of apoptosis, diltiazem was found to have the most deleterious effects on internal thoracic artery graft segments. Of the analyzed medical agents, nitroprusside was found to have the least apoptotic activity, followed by papaverine. Diabetes did not have significant effect on the occurrence of apoptosis in left internal thoracic artery grafts.

TeleCondutas: fissura anal / TeleGuides: anal fissure

A fissura anal é uma laceração do revestimento do canal anal inferior. É uma das patologias benignas anorretais mais comuns e, em muitos casos, resolve-se espontaneamente. Sua prevalência é igual entre os sexos e é mais comum em adultos jovens. A grande maioria das fissuras são primárias e causadas por trauma local, como constipação, diarreia ou sexo anal. Fissuras secundárias são encontradas em pacientes com Doença de Crohn, malignidades (neoplasia epidermoide do canal anal, leucemia), tuberculose ou doenças sexualmente transmissíveis (HIV, sífilis, clamídia). Esta guia apresenta informação que orienta a conduta para casos de fissura anal no contexto da Atenção Primária à Saúde, incluindo: classificação, avaliação clínica, diagnóstico, tratamento clínico, tratamento cirúrgico e encaminhamento para especialista.

Development and validation of a stability indicating HPLC method to determine diltiazem hydrochloride in tablets and compounded capsules

ABSTRACT A stability indicating HPLC method to determine diltiazem hydrochloride (DTZ) in tablets and compounded capsules was developed and validated according to Brazilian and the International Conference on Harmonization (ICH) guidelines. The separation was carried out on a Purospher Star® C18 (150 x 4.6 mm i.d., 5 µm particle size, Merck Millipore) analytical column. The mobile phase consisted of a 0.05% (v/v) trifluoroacetic acid aqueous solution and a 0.05% trifluoroacetic acid methanolic solution (44:56, v/v). The flow rate was 1.0 mL.min-1 with a run time of 14 minutes. The detection of DTZ and degradation products (DP) was performed at 240 nm, using a diode array detector. The method proved to be linear, precise, accurate, selective, and robust, and was adequate for stability studies and routine quality control analyses of DTZ in tablets and compounded capsules.

Impact of Diltiazem Alone versus Diltiazem with Nitrate on Five-Year Clinical Outcomes in Patients with Significant Coronary Artery Spasm

PURPOSE: Calcium channel blockers diltiazem and nitrate have been used as selective coronary vasodilators for patients with significant coronary artery spasm (CAS). However, no study has compared the efficacy of diltiazem alone versus diltiazem with nitrate for long-term clinical outcomes in patients with CAS. MATERIALS AND METHODS: A total of 2741 consecutive patients without significant coronary artery disease with positive CAS by acetylcholine (Ach) provocation test between November 2004 and May 2014 were enrolled. Significant CAS was defined as a narrowing of >70% by incremental intracoronary injection of 20, 50, and 100 µg of Ach into the left coronary artery. Patients were assigned to either the diltiazem group (n=842) or the dual group (diltiazem with nitrate, n=1899) at physician discretion. To adjust for potential confounders, a propensity score matching (PSM) analysis was performed using the logistic regression model. After PSM analysis, two well-balanced groups (811 pairs, n=1622, C-statistic=0.708) were generated. RESULTS: At 5 years, there were similar incidences in primary endpoints, including mortality, myocardial infarction, revascularization, and recurrent angina requiring repeat coronary angiography between the two groups. Diltiazem alone was not an independent predictor for major adverse cardiovascular events or recurrent angina requiring repeat coronary angiography. CONCLUSION: Despite the expected improvement of endothelial function and the relief of CAS, the combination of diltiazem and nitrate treatment was not superior to diltiazem alone in reducing mortality and cardiovascular events up to 5 years in patients with significant CAS.

Calcinosis cutis extensa en pacientes adultos con dermatomiositis: a propósito de dos casos / Extensive calcinosis cutis in adult patients with dermatomyositis: two case reports

La calcinosis cutis es el término empleado para describir una serie de trastornos caracterizados por presentar depósitos de sales de calcio a nivel subcutáneo o de la dermis, ocurriendo tanto en hipercalcemia como en normocalcemia y en ocasiones se asocia a un trastorno subyacente. El pronóstico suele ser benigno y el tratamiento, tanto médico como quirúrgico, presenta resultados variables. Presentamos dos casos de pacientes adultos con diagnóstico de dermatomiositis que desarrollaron extensas zonas de calcificación subcutánea.

Calcinosis cutis is the term used to describe a group of disorders characterized by calcium deposits in the skin, occurring in hypercalcemia or normocalcemia and sometimes associated to an underlying disorder. It has a benign evolution and the treatment, both medical and surgical, present variable outcomes. We report the cases of two adult patients with diagnosis of dermatomyositis that developed extensive areas of calcium deposit.

Comparison of internal sphincterotomy with topical diltiazem for post-hemorrhoidectomy pain relief: a prospective randomized trial.

AIM: To assess the efficacy of internal sphincterotomy compared with application of topical 2% Diltiazem ointment after hemorrhoidectomy for pain relief. SETTINGS AND DESIGN: Prospective randomized study. MATERIALS AND METHODS: In an 18-month period, 108 subjects with uncomplicated Grade 3/ 4 hemorrhoids were enrolled in the study and were randomized into two equal groups: Subjects in Group A underwent internal sphincterotomy at time of primary surgery while those in Group B received 1 g of 2% Diltiazem ointment locally, thrice daily for seven days. Postoperative pain perception was measured using visual analog score (VAS) and on the basis of number of analgesic tablets (Tab tramadol 50 mg) required in each group. Time to discharge, time to return to work and incidence of complications measured and compared. STATISTICAL ANALYSIS USED: Statistical techniques applied were Student T test, Chi-square and Fisher's Exact Test. RESULTS: There were 102 analyzable subjects (Group A: 50 and Group B: 52). The mean VAS score was significantly less in the internal sphincterotomy group from the fourth postoperative day onwards compared to topical Diltiazem (2.23 vs. 3.72; P =0.031). Similarly, the mean requirement of analgesic tablets [10.54 vs. 15.40; P =0.01] was much lower in Group A. There was no significant difference in terms of time to discharge and time to return to work between the two groups. The incidence of complications was more with the internal sphincterotomy group (11.5% vs. 3 %; P =0.488). CONCLUSIONS: In patients undergoing hemorrhoidectomy, addition of surgical internal sphincterotomy results in lesser pain in the postoperative period as compared to those receiving topical application of Diltiazem.

Ponte miocárdica multiarterial: apresentações clínica e anatômica incomuns / Multi-arterial myocardial bridge: uncommon clinical and anatomical presentations

Homem de 42 anos, sem fatores de risco para doença arterial coronariana, internado com precordialgia atípica. Eletrocardiograma após a introdução de nitrato endovenoso evidenciou supradesnivelamento do segmento ST de V1 a V4. Cineangiocoronariografia demonstrou ponte miocárdica nas três artérias coronárias além de extensão incomum na descendente anterior (80 mm). A evolução foi satisfatória com a suspensão do nitrato e instituição de betabloqueador e antagonista de canais de cálcio.

We report the case of a 42-year-old man with no risk factors for coronary artery disease admitted with atypical chest pain. The electrocardiogram performed after intravenous injection of nitrate revealed ST-segment elevation in leads V1 to V4. The coronary angiography showed myocardial bridges in the three coronary arteries, besides an unusual length of the left anterior descending artery (80 mm). The patient progressed well following the discontinuation of nitrate use and introduction of beta-blockers and calcium channel antagonists.

HIV-associated primary pulmonary hypertension: a first case report in Thailand and literature review.

A 32-year-old woman had asymptomatic HIV infection diagnosed with primary pulmonary hypertension simultaneously. She presented after a three-month rapid progression of symptoms and hemodynamic change. Physical examination and laboratory findings were compatible with pulmonary hypertension. No sensible cause could be found for the pulmonary hypertension except the HIV seropositivity; therefore, HIV-associated primary pulmonary hypertension was diagnosed. She was treated with diltiazem and oral anti-coagulation. After four months, her functional status improved from a NYHA functional class of II to I and improved in right venticular function. Since HIV is epidemic, the authors recommend HIV testing in cases of primary pulmonary hypertension.

Chemical sphincterotomy--first line of treatment for chronic anal fissure.

Anal fissure is a common disorder which may cause symptoms at any age. Internal anal sphincterotomy is the gold standard surgical treatment which lowers the resting anal pressure and effectively heals the majority of fissures. However the post operative period may be marked by surgical risks, complications and late incidence of incontinence that is some times permanent. These complications has led to a search for alternative therapies for the treatment of chronic anal fissure. Chemical sphincterotomy has been tried using a variety of novel agents including topical glyceryl trinitrate (GTN), calcium channel blockers such as nifedipine or diltiazem and botulinum toxin. Some of these agents were found to be effective in healing chronic anal fissure with negligible side effects and are now considered as first line treatment for chronic anal fissure.

Tratamiento de la fisura anal / Treatment of the anal fissure

La fisura anal es una lesión que aparece en la porción epidérmica del canal anal, con sintomatología muy florida de dolor y sangrado defecatorio. Existen dos formas típicas, la primaria o idiopática, relacionada con la isquemia relativa del anodermo debida al incremento del tono basal esfintérico interno, y la secundaria a patologías infecciosas o del tubo digestivo. Objetivo y diseño: En los últimos años surgió el concepto de esfinterotomía química. El motivo de este trabajo es la comparación entre estas técnicas incruentas y la esfinterotomía quirúrgica, evaluando en forma prospectiva randomizada los pacientes tratados con diltiazem al 2 por ciento en vaselina sólida, trinitrato de glicerilo aplicados tópicamente y la esfinterotomía lateral interna.Material y Métodos: Durante el período comprendido entre el 31 de diciembre de 2002 y el 31 de diciembre de 2004 se trataron 174 pacientes; 56 con diltiazem al 2 por ciento, 60 con trinitrato de glicerilo y 58 por medio de esfinterotomía lateral interna 10 abierta y 48 cerrada, (Nottaras). La ubicación de la fisura fue en el 76.8 por ciento o 134 pacientes en hora VI, y en el 23.2 por ciento o 40 en hora XII. La distribución según sexo fue 96 (55.3 por ciento) varones y 78 ( 44.7 por ciento) mujeres. Resultados: Luego de una media de seguimiento de 87 días (7 a 330 días), en el grupo tratado con diltiazem, 33 pacientes presentaron la desaparición de los síntomas en la primer semana, con una curación y epitelización, sin recidiva, en 38 pacientes a las 6 semanas. 7 pacientes evolucionaron mal y necesitaron cirugía, y 9 no se presentaron al control y seguimiento.En el grupo tratado con trinitrato de glicerilo, 36 pacientes tuvieron una buena evolución, 5 necesitaron cirugía, 10 no volvieron a control y 9 suspendieron el tratamiento por reacciones adversas. El grupo de 58 pacientes tratado quirúrgicamente evolucionó favorablemente excepto 2 de ellos que necesitaron una anoplastía con deslizamiento de colgajo. Conclu...

Atenolol y diltiazem como alternativas terapéuticas en pacientes digitalizados con fibrilación auricular crónica con respuesta ventricular rápida / Atenolol and diltizem as a therapeutic alternative for patients scanned with chronic atrial fibrillation with rapid ventricular responce

En este estudio se evaluó la eficacia del atenolol y diltiazen en pacientes digitalizados que acudieron a la consulta de cardiología del Hospital Universitario "Antonio María Pineda" con fibrilación auricular crónica y respuesta ventricular rápida en el lapso comprendido Agosto 2000 - Agosto 2001. Se realizó un estudio clínico controlado doble ciego y se constituyeron dos grupos en forma aleatoria de diez pacientes cada uno. Los criterios de inclusión fueron: diferentes sexos, edad entre 40-80 años, EKG con fibrilación auricular crónica con respuesta ventricular rápida y valores normales de urea creatinina, enzimas hepáticas, pruebas de funcionalismo tiroideo, digoxinemia y electrolitos séricos (Na, K, Ca, Mg). Las dosis de atenolol y diltiazem fueron de 50 mg al día y 60 más dos veces al día respectivamente. En el grupo de pacientes que recibió diltiazem se observó que la reducción de la frecuencia cardíaca mínima y máxima, así como el aumento de la fracción de eyección del ventrículo izquierdo fueron estadísticamente significativas con el valor de P= 0.005; P= 0,001 y P= 0.014 respectivamente. En el grupo de pacientes que recibió atenolol se observó que sólo el descenso de la frecuencia cardíaca máxima fue estadísticamente significativo (P= 0.029). Queda demostrado que la combinación diltiazem-digoxina en nuestro grupo de pacientes es más eficaz que atenolol-digoxina en controlar la FA crónica con respuesta ventricular rápida, así como mejorar la fracción de eyección determinada por ecocardiografía.

Refractory adenosine-sensitive congenital His bundle tachycardia: response to calcium-channel blockers.

The congenital form of His bundle tachycardia is an uncommon pediatric arrhythmia. We report the case of a 7-year-old child with tachycardiomyopathy. The incessant arrhythmia, detected in infancy, was resistant to amiodarone and beta-blockers. During electrophysiologic study, the tachycardia converted to sinus rhythm with intravenous adenosine and diltiazem. Subsequently, the child is maintaining sinus rhythm on oral verapamil. Calcium-channel blockers should be considered for the treatment of this arrhythmia, which is often resistant to multiple antiarrhythmic drugs.

Comparaçäo entre os efeitos da clortalidona e do diltiazem sobre a isquemia miocárdica em idosos hipertensos portadores de doença arterial coronariana / Effects of chlorthalidone and diltiazem on myocardial ischemia in elderly patients with hypertension and coronary artery disease

OBJECTIVE: Antihypertensive therapy with thiazides decreases coronary events in elderly patients. However, the influence of diuretics on myocardial ischemia has not been fully investigated. The aim of this study was to compare the effect of chlorthalidone and diltiazem on myocardial ischemia. METHODS: Following a randomized, double-blind, crossover protocol, we studied 15 elderly hypertensive patients aged 73.6 + or - 4.6 years with myocardial ischemia. All patients had angiographically documented coronary artery disease. We measured patients using 48- hour ambulatory electrocardiogram monitoring and exercise testing. After a 2-week period using placebo, patients received chlorthalidone or diltiazem for 4 weeks. RESULTS: Both treatments lowered systolic and diastolic blood pressures...

Angina inestable: los calcibloqueantes sin betabloqueantes no previenen la recurrencia de la angina, los procedimientos intervencionistas, ni la insuficiencia cardíaca / Calcium channel bloquer agentes, not associated to betabloquers, do not prevent recurrent angina, further invasive procedures or pump failure in patients hospitalized for unstable angina

Antecentes. Los calciantagonistas (CA) deberían ser eficaces en reducir la mortalidad y el infarto (IAM) no fatal en la angina inestable (AI). Se ha demostrado que los CA proporcionan alivio sintomático y mejor evolución. Objetivo. Investigar si los CA en la AI disminuyen la muerte y el IAM no fatal, previenen la recurrencia de la angina y mejoran la evolución. Material y métodos. Análisis en la base de datos del estudio ENAI (Enalapril en la Angina Inestable) que sigue durante 7 días a 1022 pacientes con AI. Indicación de betabloqueantes (BB) y CA a criterio de los participantes. Resultados. La angina recurrente y los procedimientos invasivos no son diferentes en la AI previamente tratada con CA (RR 1,02; IC95 0,74 - 1,40; P 0,8958). En 1022 pacientes los eventos secundarios aumentan en los no tratados (53,3 por ciento en 629) en relación a los tratados con CA cuando se asocian a los BB (46,7 por ciento en 392; RR 1,39; IC95 1,19 - 1,62; P 0,00003) Para Diltiazem-BB los eventos secundarios disminuyen desde un 61,3 por ciento al 38,7 por ciento (RR 1,74; ; IC95 1,39 - 2,18; P 0,0000), similar con otros CA-BB. Reducen los eventos secundarios del 66 por ciento al 34 por ciento en el grupo con SD del ST/ST normal (RR del 1,92; IC95 1,05 - 3,51; P 0,0335). Conclusiones. La indicación de CA sin BB en AI no disminuye los eventos isquémicos secundarios ni el desarrollo de insuficiencia cardíaca. Indicados en AI con SD del ST.

A comparison of esmolol & diltiazem for heart rate control during coronary revascularisation on beating heart.

This prospective study was done to compare the control of heart rate and haemodynamics during coronary artery revascularisation without cardiopulmonary bypass using either esmolol or diltiazem. Sixty adult patients with one or two vessel coronary artery disease, were randomly divided into 2 equal groups. Group A received a 500 micrograms/kg loading dose of esmolol followed by a 100 micrograms/kg/h infusion, for control of heart rate during surgical anastomosis of the coronary vessel. While Group B received 0.15 mg/kg diltiazem as a loading dose followed by a 5 mg/h infusion for heart rate control, during the anastomosis. It was seen that heart rate control was better in Group A, 51.4 (+/- 1.3) beats/min, than in Group B, 69.6 (+/- 3.9) beats/min but the decrease in heart rate was significant in both the groups at peak effect compared to respective predrug values. Group A patients had unchanged systemic resistance and pulmonary artery wedge pressure but mean pulmonary artery pressure and pulmonary vascular resistance were significantly raised. Group B patients had decreased systemic resistance, mean pulmonary artery pressure and pulmonary artery wedge pressure, and reduced right ventricular stroke work index. We concluded that although esmolol provided dramatically slower heart rates, during surgery, the resulting elevations in mean pulmonary artery pressure and pulmonary vascular resistance would require caution if used in patients with underlying right ventricular dysfunction from ischaemia or infarction. Diltiazem by virtue of its effects on systemic vascular resistance, cardiac output, and lowering of mean arterial pressure may be a better choice in hypertensive patients.

Neutrophil signaling alteration: an adverse inflammatory response after burn shock

The inflammatory response syndrome in shock-like states might frequently be accompained by an oxidative cell/tissue demage in one or more organ-systems in the body. The inflammatory response related hyperactivation of neutrophils can contribute to oxidative cell/tissue damage. Studies discussed in this review examined the role of cell sgnaling pathways in the hyperactivation of neutrophils in an early stage of burn injury shock. The studies were carried out in peripheral blood neutrophils isolated from rats with a 25 per cent body surface area scald burn. Neutrophil cell signaling responses were evaluated by measuring cytosolic [Ca2+] and protein kinase C activity, and were correlated with neutrophil superoxide production. The cytosolic [Ca2+] and protein kinase C responses were highly upregulated along with enhanced superoxide production in the early phase of burn injury. The treatment of burn-injured rats with the calcium antagonist diltiazem abrogated enhanced Ca2+ and protein kinase C signaling and superoxide generation. The signaling upregulation in neutrophils could result from potentiation of actions of burn-injury induced chemotactic mediators on the leukocytes. The neutrophil signaling upregulation leading to increased superoxide generation could thus be responsible for the oxidative cell/tissue damage. The organ-system dysfunction/failure accompanying burn shock may be initiated with the oxidative cell/tissue damage.

Revascularización miocárdica con conductos arteriales: arteria radial en combinación con arterias mamarias / Myocardial revascularization with arterial conduits: combined use of radial and internal mammary arteries

Se presentan los resultados de 123 pacientes sometidos a cirugía de revascularización miocárdica utilizando conductos arteriales: arterias mamarias y arteria radial. La mamaria izquierda casi siempre es empleada para revascularizar el territorio de la arteria descendente anterior y generalmente in situ, mientras que con la derecha se revascularizó las áreas dependientes de coronaria derecha y circunfleja; finalmente la arteria radial se destinó a los territorios del ramo diagonal, circunfleja y a veces de la descendente posterior. La arteria radial estuvo disponible para realizar anastomosis múltiples debido a su extensión aproximada de 20 cm. Asimismo el empleo combinado de estos tres conductos arteriales permite una revascularización arterial exclusiva en la mayoría de los pacientes operados con una baja morbimortalidad temprana y alejada