A case of spontaneous pneumomediastinum and pneumopericardium in a young adult.

Spontaneous medialstinal emphysema (pneumomediastinum) and pneumopericardium may be defined as the presence of free air or gas in the mediastinal structures and in the pericardial sac without an apparent precipitating cause. It most frequently occurs in young healthy adults without serious underlying pulmonary disease. Although pneumomediastinum and pneumopericardium is often asymptomatic, it may cause pain in the neck and chest, dysphonia and shortness of breath. Treatment is supportive unless the patient has a history of trauma from foreign body aspiration. The course of spontaneous pneumomediastinum and pneumopericardium is usually benign and self-limited. A case of spontaneous pneumomediastinum, pneumopericardium and subcutaneous emphysema in a 20-year-old male is reported in this paper.

Recurrent asystoles associated with vasovagal reaction during venipuncture.

A 17-year-old high school student presented with a history of habitual faintings. On 24-hour Holter monitoring, cardiac asystoles were recorded, the longest lasting approximately 7 or 8 seconds during venipuncture procedures. The asystole associated with venipuncture demonstrated the cardioinhibitory effects of vasovagal reaction with blood-injury phobia. He also had a positive response during head-up tilt test showing hypotension and relative bradycardia after intravenous isoproterenol injection. After administration of oral beta blocker, he did not show further or recurrent cardiac asystole during blood injury procedure on electrocardiographic examination. Venipuncture is the most common invasive medical procedure performed in hospital settings. While venipuncture is considered to be reasonably safe, serious complication may occur even when only a small volume of blood is withdrawn. Therefore, medical personnel should be prepared to provide appropriate care.

Anti-Helicobacter pylori activity of quinolone alkaloids from Evodiae fructus.

A biologically monitored fractionation of methanol extract of the fruit of Evodia rutaecarpa led to the isolation of six quinolone alkaloids, evocarpine (1), 1-methyl-2-[(4Z,7Z)-4,7-tridecadienyl]-4(1H)-quinolone (2), 1-methyl-2-[(6Z,9Z)-6,9-pentadecadienyl]-4(1H)-quinolo ne (3), 1-methyl-2-undecyl-4(1H)-quinolone (4), dihydroevocarpine (5), 1-methyl-2-pentadecyl-4(1H)-quinolone (6). They showed potent anti-Helicobacter pylori activity with the minimum inhibitory concentration (MIC) value of 10-20 microg/ml. However, they had no effect on Helicobacter pylori urease activity at the concentration of 300 microg/ml.

Transesophageal echocardiographic detection of thoracic aortic plaque could noninvasively predict significant obstructive coronary artery disease.

OBJECTIVE: Previous pathologic and roentgenographic studies have suggested a relation between aortic plaque and coronary artery disease but have lacked clinical utility. The study was undertaken to elucidate whether atherosclerotic aortic plaque detected by transesophageal echocardiography can be a clinically useful marker for significant obstructive coronary artery disease. METHODS: Clinical and angiographic features and intraoperative transesophageal echocardiographic findings were prospectively analyzed in 131 consecutive patients (58 women and 73 men, aged 17 to 75 years [mean 54 +/- 12]) undergoing open heart surgery. Significant obstructive coronary artery disease was defined as > or = 50% stenosis of > or = 1 major branch. RESULTS: Seventy-six (58%) of 131 patients were found to have obstructive coronary artery disease. In 76 patients with significant coronary artery disease, 71 had thoracic aortic plaque. In contrast, aortic plaque existed in only 10 of the remaining 55 patients with normal or minimally abnormal coronary arteries. The presence of aortic plaque on transesophageal echocardiographic studies had a sensitivity of 93%, a specificity of 82% and positive and negative predictive values of 88% and 90%, respectively, for significant coronary artery disease. There was a significant relationship between the degree of aortic intimal changes and the severity of coronary artery disease (r = 0.74, P < 0.0001). Multivariate logistic regression analysis of patient age, sex, risk factors of cardiovascular disease and transesophageal, echocardiographic findings revealed that atherosclerotic aortic plaque was the most significant independent predictor of coronary artery disease. CONCLUSION: This study indicates that transesophageal echocardiographic detection of atherosclerotic plaque in the thoracic aorta is useful in the noninvasive prediction of the presence and severity of coronary artery disease.

Inhibitory activity of monoamine oxidase by coumarins from Peucedanum japonicum.

Four coumarins were isolated from chloroform extract of the root of Peucedanum japonicum and identified as praeruptorin A(1), xanthotoxin (2), psoralen (3) and bergapten (4) on the basis of spectroscopic methods. The inhibitory activities of these coumarins on monoamine oxidase prepared by mouse brain were tested. The IC50 values of them were shown to be 27.4 microM (1), 40.7 microM (2), 35.8 microM (3), and 13.8 microM (4), in vitro.

Influence of some novel N-substituted azoles and pyridines on rat hepatic CYP3A activity.

A series of N-substituted heteroaromatic compounds structurally related to clotrimazole was synthesized, and the effects of these compounds on ethosuximide clearance in rats were determined as a measure of their abilities to induce cytochrome P4503A (CYP3A) activity. Ethosuximide clearance and in vitro erythromycin N-demethylase activity were shown to correlate. In this series, imidazole or other related heteroaromatic "head groups" were linked to triphenylmethane or other phenylmethane derivatives. Within the series, it was found that 1-triphenylmethane-substituted imidazoles elicited the greatest increase in CYP3A activity, and that among the triphenylmethyl-substituted imidazoles, the highest activities were achieved by the substitution of F- or Cl- in either the meta or para position of one of the phenyl rings. Diphenylmethyl-substituted pyridine was effectively devoid of activity. Compounds eliciting the largest increase in CYP3A activity (viz. 1-[(3-fluorophenyl)diphenylmethyl]imidazole, 1-[(4-fluorophenyl)diphenylmethyl]imidazole, and 1-[tri-(4-fluorophenyl)methyl]imidazole) produced little or no increase in ethoxyresorufin O-dealkylase (EROD) activity (i.e. CYP1A), whereas benzylimidazole, which elicited only a small increase in CYP3A activity, produced an almost 9-fold increase in CYP1A activity. For a series of eleven compounds exhibiting a wide range of influence on CYP3A activity, a positive correlation was found between ethosuximide clearance and hepatic CYP3A mRNA levels.

Synthesis and biological characterization of 1,4,5,6-tetrahydropyrimidine and 2-amino-3,4,5,6-tetrahydropyridine derivatives as selective m1 agonists.

Previous studies identified several novel tetrahydropyrimidine derivatives exhibiting muscarinic agonist activity in rat brain. Such compounds might be useful in treating cognitive and memory deficits associated with low acetylcholine levels, as found in Alzheimer's disease. To determine the molecular features of ligands important for binding and activity at muscarinic receptor subtypes, the series of tetrahydropyrimidines was extended. Several active compounds were examined further for functional selectivity through biochemical studies of muscarinic receptor activity using receptor subtypes expressed in cell lines. Several amidine derivatives displayed high efficacy at m1 receptors and lower activity at m3 receptors coupled to phosphoinositide (PI) metabolism in A9 L cells. Four ligands, including 1b, 1f, 2b, and 7b, exhibited marked functional selectivity for m1 vs m3 receptors. Compound 1f also exhibited low activity at m2 receptors coupled to the inhibition of adenylyl cyclase in A9 L cells. Molecular modeling studies also were initiated to help understand the nature of the interaction of muscarinic agonists with the m1 receptor using a nine amino model of the m1 receptor. Several important interactions were identified, including interactions between the ester moiety and Thr192. Additional interactions were found for oxadiazoles and alkynyl derivatives with Asn382, suggesting that enhanced potency and selectivity may be achieved by maximizing interactions with Asp105, Thr192, and Asn382. Taken together, the data indicate that several amidine derivatives display functional selectivity for m1 muscarinic receptors, warranting further evaluation as therapeutic agents for the treatment of Alzheimer's disease. In addition, several amino acid residues were identified as potential binding sites for m1 agonists. These data may be useful in directing efforts to develop even more selective m1 agonists.

[Immunological properties of the 30 kDa antigen of toxoplasma gondii].

The molecular weight 30 kDa membrane protein of Toxoplasma gondii (Toxoplasma 30 kDa) apparently conserved in most strains of T. gondii and sera of infected hosts. The present study aimed to elucidate Toxoplasma 30 kDa as a useful diagnostic antigen for serodiagnosis of toxoplasmosis by ELISA and for induction of protective immunity. Murine spleen cells immunized with the membrane antigen of T. gondii were fused with mouse Sp2/O-Ag14 myeloma cells. Out of 8 clones selected, five were IgG2b, the others belonged to IgG1 and IgG2a. The 30 kDa antigen was distributed mainly on the surface membrane of tachyzoites by indirect fluorescence method. Murine peritoneal macrophages which were activated by 30 kDa antigen produced more amounts of NO2 compared with crude antigen-treated group, however there were no significant differences in toxoplamacidal activity between the two groups. Higher specificity of Toxoplasma 30 kDa antigen was recognized for serodiagnosis of toxoplasmosis than the crude antigen. From these results, Toxoplasma 30 kDa antigen enhances the cytotoxic effect of macrophages as well as a more reliable means for the serodiagnosis of toxoplasmosis by ELISA.

Amiodarone instilled into the canine pericardial sac migrates transmurally to produce electrophysiologic effects and suppress atrial fibrillation.

INTRODUCTION: We investigated whether amiodarone delivered into the pericardial sac exerted an effect on atrial and ventricular refractoriness, impulse generation, and conduction and on induced atrial fibrillation. METHODS AND RESULTS: All animals were anesthetized with alpha-chloralose. After a sternotomy, the pericardium was opened and cradled to produce a "container" of approximately 75 mL. Part I experimental animals received amiodarone, 0.5, 1.0, or 5.0 mg/mL, dissolved in 3 mL polysorbate 80 and 5% dextrose in water (D5W) instilled into their pericardial sac for 3-hour intervals. Part II experimental animals received either 1.0 or 5.0 mg/mL of amiodarone. Control dogs received a pericardial solution of 3 mL polysorbate 80 in D5W. Pre- and postinstillation electrophysiologic studies were performed. In part I, the increase in sinus cycle length, 1:1 AV conduction, and effective refractory period (ERP) of atrium, right ventricular (RV) and left ventricular epicardium, and RV endocardium were significantly greater in animals receiving amiodarone compared with controls. Amiodarone concentrations in the tissue samples were highest in the superficial sites of the atria, sinoatrial node, and ventricular epicardial samples and lowest in the interventricular septum. Only trace concentrations of amiodarone and no desethylamiodarone were found in the blood samples. In part II, atrial ERP significantly increased in the animals receiving amiodarone, and the number of episodes of sustained atrial fibrillation that could be induced decreased. CONCLUSIONS: Amiodarone instilled into the pericardial sac migrates transmurally to produce significant electrophysiologic effects at superficial sites and appears to suppress electrically induced atrial fibrillation.

Microwave ablation of canine atrial tachycardia induced by aconitine.

We tested the efficacy of microwave-frequency energy for ablating atrial tachycardia in eight open-chest dogs. Five other dogs served as controls. Atrial tachycardia was induced by direct application of aconitine crystals to the epicardial atrial surface or by injection of aconitine solution (0.15 mg/ml) into the right or left atrial myocardium. Atrial tachycardias (n = 15) developed at a cycle length of 253 +/- 64 msec or within 245 +/- 116 sec after topical application or injection of aconitine. Catheter ablation was attempted on 10 atrial tachycardias in 8 experiment dogs by using continuous, unmodulated microwave energy from a 915 MHz frequency signal generator via a 7F helical or whip antenna catheter. Successful ablation was defined as conversion of atrial tachycardia to sinus rhythm during delivery of microwave energy and maintenance of sinus rhythm for > 5 minutes after termination of energy delivery. All 10 atrial tachycardias were successfully ablated by 2.3 +/- 1.6 applications of microwave energy for each atrial tachycardia induced. Forward microwave power level was 50.5 +/- 8.1 W, and the duration of energy application was 25.0 +/- 27.6 seconds. Sinus rhythm resumed 9.5 +/- 9.2 seconds after the onset of microwave energy application. After a mean follow-up of 10.4 minutes, seven atrial tachycardias recurred, most likely the result of diffusion of aconitine beyond the perimeter of rhe ablation lesions. Atrial tachycardia did not recur in 3 of 3 dogs that had larger ablation lesion. Gross examination revealed 10 demarcated round or oval transmural lesions in the right or left atrium, ranging from 12.6 to 105.6 mm2 in area.(ABSTRACT TRUNCATED AT 250 WORDS)

Design, synthesis, and neurochemical evaluation of 2-amino-5-(alkoxycarbonyl)-3,4,5,6-tetrahydropyridines and 2-amino-5-(alkoxycarbonyl)-1,4,5,6-tetrahydropyrimidines as M1 muscarinic receptor agonists.

Four regioisomers of 2-amino-(methoxycarbonyl)-3,4,5,6-tetrahydropyridine (2a-5a) were synthesized as the racemates to evaluate the utility of exocyclic amidines in the development of novel agonists for M1 muscarinic receptors. Of the four regioisomers, only racemic 2-amino-5-(methoxycarbonyl)-3,4,5,6-tetrahydropyridine (4a; CDD-0075-A) displayed high affinity (IC50 = 10 +/- 3.0 microM) and activity at muscarinic receptors coupled to PI metabolism in the rat cortex (260 +/- 4.5% stimulation above basal levels at 100 microM). A series of 2-amino-5-(alkoxycarbonyl)-3,4,5,6-tetrahydropyridines then was synthesized for further evaluation as M1 agonists. Only the propargyl derivative (4d) retained substantial agonist activity (120 +/- 14% at 100 microM) in this series. On the basis of the activity of the 5-(alkoxycarbonyl)-1,4,5,6- tetrahydropyrimidines (1a and 1d) and the 2-amino-5-(alkoxycarbonyl)-3,4,5,6-tetrahydropyridines, the corresponding cyclic guanidine derivatives were synthesized and tested. 2-Amino-5-(methoxycarbonyl)-1,4,5,6-tetrahydropyrimidine (7a) displayed a modest affinity for muscarinic receptors in the CNS (22 +/- 5.3 microM) and an ability to stimulate PI turnover in rat cerebral cortex (81 +/- 16% at 100 microM). The propargyl derivative (7d) also had modest binding affinity (31 +/- 15 microM) and high activity (150 +/- 8.5% at 100 microM), as expected based on the activity of propargyl esters of 1,4,5,6-tetrahydropyrimidine and 2-amino-3,4,5,6-tetrahydropyridine. Computational chemical studies revealed five distinct minimum-energy conformations for 1a, (R)-4a, and 7a, and three for 1d, (R)-4d, and 7d, each with a unique orientation of the ester moiety. Each of the five conformations for 1a could be superimposed upon a unique conformer of (R)-4a and 7a, suggesting that the compounds interact with muscarinic receptors in a similar fashion. Taken together, the data indicate the general utility of amidine systems as suitable replacements for the ammonium group of acetylcholine in developing ligands with activity at M1 muscarinic receptors in the central nervous system. Such compounds might be useful in the treatment of patients with Alzheimer's disease.