Amiodarone versus Implantable Defibrillator (AMIOVIRT): Background, Rationale, Design, Methods, Results and Implications

Non ischemic dilated cardiomyopathy (NIDCM) is a substrate for sudden cardiac death. Treatment with amiodarone may have a positive or neutral survival benefit. The role of ICD therapy in the primary prevention of sudden cardiac death in asymptomatic NIDCM patients is not clear. The purpose of the Amiodarone versus Implantable Defibrillator (AMIOVIRT) study was to compare total mortality, arrhythmia-free survival, quality of life and costs of therapy in patients with NIDCM, asymptomatic non-sustained ventricular tachycardia (NSVT) and left ventricular ejection fraction 相似文献   

Threshold parameters of left main coronary artery stem stenosis based on intracoronary ultrasound examination

INTRODUCTION: The left main coronary stem (LMS) provides blood supply to the left ventricle, and its stenosis is associated with serious clinical consequences. The accurate assessment of LMS stenosis determines appropriate treatment and long term prognosis. So far no criteria have been established to correctly estimate the magnitude of problematic lesions as indicated by quantitative angiography (QCA). AIM: An attempt to establish intracoronary ultrasound (ICUS) threshold values of significant LMS stenosis. METHODS: The studied group consisted of 197 patients (mean age 69.72+/-8.51) who underwent percutaneous coronary intervention (PCI) of the left coronary artery. Group 1 (G1) consisted of 99 patients who had LMS diameter reduction (%DS) of less than 30%. Group 2 (G2) consisted of 77 patients with %DS between 30% and 50%, and the remaining 21 patients with %DS higher than 50% were classified as Group 3 (G3). The quantitative angiography (QCA) analysis included lumen diameter (Ldmin) which was LMS lumen diameter at the most stenotic segment as well as LMS diameter reduction (%DS). The parameters that were analysed during ICUS study included maximum plaque burden (%) (Pbmax), minimal lumen area (LAmin) and lumen stenosis (%LS) calculated according to the formula: (LAmin/LAref) x 100%. Additionally, correlations between the corresponding parameters measured using QCA and ICUS were investigated. RESULTS: Both diagnostic techniques showed the most advanced degree of atherosclerosis in G3. All the G3 patients and 5 G2 patients had MLD values less than or equal to 2 mm. In G1 LAmin values exceeded 9 mm(2) in all patients, whereas among G2 patients 12 (15.5%) had LAmin lower than 6 mm(2), 29 pts. (37.66%) within the range of 6-9 mm(2) and in the remaining 36 pts. (46.75%) it exceeded 9 mm(2). In G3 LAmin values in 17 pts. (80.95%) did not exceed 6 mm(2) and in the remaining 4 pts. (19.05%) were slightly higher. Lumen reduction higher than 50% was noted in all G3 patients and 3 G2 patients (in all these 3 G2 patients LAmin values were lower than 6 mm(2)). All G3 pts. and 3 G2 pts. with LAmin value <6 mm(2) and %LS >50% had angina and a positive stress ECG test. All of these patients (n=24) underwent LMS stent implantation. CONCLUSIONS: 1. Minimal lumen diameter of LMS < or = 2 mm in quantitative angiography indicates a very high probability of significant stenosis of this vessel. 2. Ultrasound data analysis shows that besides LMS lumen area (<9 mm(2)) stenosis significance is determined by lumen reduction of more than 50%.     

Time Course and Reversibility of Ethanol''s Suppressive Effects on Axon Sprouting in the Dentate Gyrus of the Adult Rat

Ethanol was administered chronically to adult rats in a liquid diet for 14 days preceding and for 5, 7, 8, 9, or 10 days following the unilateral destruction of the entorhinal cortex. Control groups received a diet of lab chow and water and were sacrificed at comparable survival times. An additional experimental group was given ethanol until 9 days after the lesion, then switched to lab chow and water and sacrificed 1 day later. Coronal sections through the dorsal hippocampal formation were stained and analyzed histochemically for the localization of acetylcholinesterase (AChE). Quantitative measurements of the histochemical patterns in the molecular layer of the dentate gyrus were obtained. Ethanol exposure inhibited the withdrawal of the acetylcholinesterase-stained septohippocampal fibers and limited the typical lesion-induced expansion of the pale-staining commissural/associational zone in the molecular layer of the denervated dentate gyrus. However, abstinence from ethanol for just 24 h released the inhibitory effect on the acetylcholinesterase-staining fibers, resulting in a significant expansion of the commissural/associational zone.     

Blood Pressure and Alcohol Intake in Heart Patients

The association between alcohol consumption and blood pressure has been studied in 2025 male and 282 female patients undergoing diagnostic coronary angiography. The increase in amount of alcohol consumed correlated with higher systolic and diastolic blood pressure; this effect was especially pronounced in men over 50 years of age. The association was less marked in male patients under 50 years old, in women, and in patients on antihypertensive medication. Readings in the range of definitive hypertension were more prevalent among older patients consuming six or more drinks daily than in abstainers of the same age group.     

p16INK4A and p15INK4B gene deletions in primary leukemias

The 9p21 locus has been deleted at a high frequency in a wide variety of tumors. Recently, two genes, p16INK4A and p15INK4B (also called MTS1 and MTS2), have been localized in close proximity at the 9p21 locus, encoding cyclin-dependent kinases 4/6 inhibitors of relative molecular mass 16 kD and 15 kD, respectively and also found to be deleted at a high frequency in tumor cell lines. We analyzed p16INK4A and p15INK4B genes in 178 cases of primary leukemias including 81 cases of chronic lymphocytic leukemia (CLL), seven of hairy cell leukemia (HCL), seven of chronic myelogenous leukemia (CML), 43 of acute myelogenous leukemia (AML), 27 of acute lymphoblastic leukemia (ALL), and 13 of myelodysplastic syndrome (MDS) by Southern blot analyses. The ALL cases showed a relatively high frequency of homozygous deletions (22%, 6 of 27) at the p16INK4A gene locus. Interestingly, of the six cases with p16INK4A homozygous deletions, only three showed homozygous deletions at the p15INK4B gene. In 81 CLL patients, we detected one homozygous and five heterozygous deletions at both the p16INK4A and p15INK4B genes and two heterozygous deletions at the p16INK4A gene alone. Deletion of these two genes in AML cases is relatively low (9%). We did not detect deletions in any of the MDS, HCL, and CML cases examined. Sequence analyses of p16INK4A gene of six CLL cases with heterozygous deletion at this locus showed a 27-bp deletion at the splice acceptor site of intron 1 in one case and changes in the coding sequence in three other cases. The data presented in this report showed that (1) p16INK4A and p15INK4B genes are preferentially deleted homozygously in ALL and heterozygously in CLL cases with frequent mutation in the second allele, and (2) p16INK4A gene appears to be more frequently deleted than p15INK4B gene.     

Chronotropic response to exercise predicts angiographic severity in patients with suspected or stable coronary artery disease

Inappropriate chronotropic response to exercise has been observed to correlate with poor prognosis in patients with coronary disease, but the mechanism for this association is not well defined. We attempted to examine the association between chronotropic response to exercise and angiographic severity of coronary disease in patients with suspected or stable coronary artery disease. The chronotropic response, expressed as peak heart rate, chronotropic index (ratio of heart rate reserve and metabolic reserve utilized), or percent maximal heart rate achieved, was correlated with angiographic findings obtained within 180 days of the test. Significant coronary disease was defined as ≥1 stenosis of ≥50% in a major epicardial artery or its main branches; severe coronary disease was defined as ≥50% stenosis in all 3 epicardial arteries, or in the left main coronary trunk, or 2-vessel disease with ≥70% proximal left anterior descending artery stenosis. We observed that peak heart rate and percent maximal heart rate achieved were independent negative predictors of both significant and severe coronary disease by logistic regression. The chronotropic index predicted severe coronary disease only. All 3 parameters of chronotropic response exhibited a significant gradient of abnormality across the spectrum of coronary disease (p < 0.01 for all), expressed by the number of vessels involved and correlated with left anterior descending artery involvement (p < 0.05 for all). We conclude that chronotropic response to exercise predicts the presence and angiographic severity of coronary disease. This association is likely related to the proportion of left ventricular myocardium rendered ischemic during stress.     

Morphological disruption of colonic mucosa by free or cholestyramine-bound bile acids

In order to assess the effects of free or resin-bound bile acids on colonic topography, adult rats were surgically provided with an indwelling infusion catheter in the proximal cecum, which exited at the neck behind the head. Conscious, unrestrained rats were allowed chowad libitum and were administered 1 ml of an infusion mixture twice daily for five days. The infusion mixtures included either carrier saline, 100 mg cholestyramine, 165 μmol mixed bile acids, or the bile acids bound to cholestyramine. Additional groups of rats were fed defined diets with and without 2% cholestyramine. Compared to fed controls, colonic infusions of saline had little effect on colon topography. Infusions of 100 mg of cholestyramine in saline twice each day did cause some apparent damage to surface morphology of the colon, but not to the extent observed during feeding of the resin as 2% of the diet. In contrast, extensive surface damage of the colon was observed by twice daily infusions of either 165 μmol of an equimolar mixture of cholic, deoxycholic, and chenodeoxycholic acids, or by the bile acids mixed previously with the ion-exchange resin. The data suggest that topographical damage of the colon observed during feeding of bile acid-sequestering resins is in large part due to increased concentrations of either bound or unbound bile acids in the large bowel.     

Analytical profile of N‐ethyl‐N‐cyclopropyl lysergamide (ECPLA), an isomer of lysergic acid 2,4‐dimethylazetidide (LSZ)

Recent investigations have shown that N‐ethyl‐N‐cyclopropyl lysergamide (ECPLA) produces LSD‐like behavioral effects in mice, which suggests that it may act as a hallucinogen in humans. Although the use of ECPLA as a recreational drug has been limited, key analytical data that can be used to detect ECPLA are required for future forensic and clinical investigations. ECPLA is an isomer of (2′S,4′S)‐lysergic acid 2,4‐dimethylazetidide (LSZ), a lysergamide that emerged as a recreational drug in 2013. Several analytical approaches were examined, including single‐ and tandem mass spectrometry platforms at low and high resolution, gas‐ and liquid chromatography (GC, LC), nuclear magnetic resonance spectroscopy (NMR), and GC condensed‐phase infrared spectroscopy (GC‐sIR). ECPLA and LSZ could be differentiated by NMR, GC‐sIR, GC, and LC‐based methods. The electron ionization mass spectra of ECPLA and LSZ contained ion clusters typically observed with related lysergamides such as m/z 150–155, m/z 177–182, m/z 191–197, m/z 205–208, and m/z 219–224. One of the significant differences in abundance related to these clusters included ions at m/z 196 and m/z 207/208. The base peaks were detected at m/z 221 in both cases followed by the retro‐Diels‐Alder fragment at m/z 292. Minor but noticeable differences between the two isomers could also be seen in the relative abundance of m/z 98 and m/z 41. Electrospray ionization mass spectra included lysergamide‐related ions at m/z 281, 251, 223, 208, 197, 180, and 140. LSZ (but not ECPLA) showed product ions at m/z 267 and m/z 98 under the conditions used.     

In vivo metabolism of the designer anabolic steroid hemapolin in the thoroughbred horse

Hemapolin (2α,3α‐epithio‐17α‐methyl‐5α‐androstan‐17β‐ol) is a designer steroid that is an ingredient in several “dietary” and “nutritional” supplements available online. As an unusual chemical modification to the steroid A‐ring could allow this compound to pass through antidoping screens undetected, the metabolism of hemapolin was investigated by an in vivo equine drug administration study coupled with GC‐MS analysis. Following administration of synthetically prepared hemapolin to a thoroughbred horse, madol (17α‐methyl‐5α‐androst‐2‐en‐17β‐ol), reduced and dihydroxylated madol (17α‐methyl‐5α‐androstane‐2β,3α,17β‐triol), and the isomeric enone metabolites 17β‐hydroxy‐17α‐methyl‐5α‐androst‐3‐en‐2‐one and 17β‐hydroxy‐17α‐methyl‐5α‐androst‐2‐en‐4‐one, were detected and confirmed in equine urine extracts by comparison with a library of synthetically derived reference materials. A number of additional madol derivatives derived from hydroxylation, dihydroxylation, and trihydroxylation were also detected but not fully identified by this approach. A yeast cell‐based androgen receptor bioassay of available reference materials showed that hemapolin and many of the metabolites identified by this study were potent activators of the equine androgen receptor. This study reveals the metabolites resulting from the equine administration of the androgen hemapolin that can be incorporated into routine GC‐MS antidoping screening and confirmation protocols to detect the illicit use of this agent in equine sports.