Safety and Preliminary Efficacy of Lorcaserin for Cocaine Use Disorder: A Phase I Randomized Clinical Trial.

Background and Objectives: Preclinical studies show serotonin (5-HT) 5-HT2C receptor (5-HT2CR) agonists reduce cocaine-seeking and cocaine intake. This study examined safety of the 5-HT2CR agonist lorcaserin administered with cocaine in participants with cocaine use disorder (CocUD). Secondarily, subjective response to cocaine and choice of cocaine vs. money were examined. Methods: A double-blind, randomized, placebo-controlled trial of 25 inpatient non-treatment seeking participants with CocUD. Participants were randomized to either lorcaserin (n = 17) or placebo (n = 8). Primary outcome measures included cardiovascular measures and plasma cocaine levels. Secondary measures of subjective response to cocaine were assessed using a visual analog scale (VAS) and cocaine vs. money progressive ratio choice sessions. Results: Thirteen randomized participants were included in the final analysis. No serious or unexpected adverse events were related to lorcaserin. There were no significant interactions between cocaine and lorcaserin on cardiovascular measures, plasma cocaine, or subjective ratings. After multiple comparisons correction, cocaine significantly increased blood pressure, heart rate, and QTc. Lorcaserin significantly decreased VAS ratings of "feel irritable," "feel hungry," and "I am craving." For the cocaine vs. money choice procedure, there was a significant interaction between choice (cocaine vs. money) and lorcaserin. Participants treated with lorcaserin were more likely to choose cocaine. Discussion and Conclusions: This study showed safety of lorcaserin administered with cocaine but lack of efficacy to reduce the reinforcing effects of cocaine. Scientific Significance: This study is the first to show a disconnect between effects of 5-HT2CR agonists on craving and cocaine choice in human cocaine users.

Prognostic utility of the assessment of diastolic function in patients undergoing cardiac resynchronization therapy.

Conflicting data exist about the relationship between cardiac resynchronization therapy (CRT) and diastolic function. Aims of the study are to assess diastolic patterns in patients undergoing CRT according to the 2016 recommendations of the American Society of Echocardiography/European Association of Cardiovascular Imaging and to evaluate the prognostic value of diastolic dysfunction (DD) in CRT candidates. METHODS AND RESULTS: One-hundred ninety-three patients (age: 67 ± 11 years, QRS width: 167 ± 21 ms) were included in this multicentre prospective study. Mitral filling pattern, mitral tissue Doppler velocity, tricuspid regurgitation velocity, and indexed left atrial volume were used to classify DD from grade I to III. CRT-response, defined as a reduction of left ventricular (LV) end-systolic volume > 15% at 6-month follow-up (FU), occurred in 132 (68%) patients. The primary endpoint was a composite of heart transplantation, LV assisted device implantation, or all-cause death during FU and occurred in 29 (15%) patients. CRT was associated with a degradation of DD in non-responders. At multivariable analysis corrected for clinical variables, QRS duration, mitral regurgitation, CRT-response and LV dyssynchrony, grade I DD was associated with a better outcome (HR 0.37, 95% CI: 0.14-0.96). Non-responders with grade II-III DD had the worse prognosis (HR 4.36, 95%CI: 2.10-9.06). CONCLUSIONS: The evaluation of DD in CRT candidates allows the prognostic stratification of patients, independently from CRT-response.

Utilizing Buprenorphine in the Emergency Department after Overdose.

The United States is currently in the midst of an opioid epidemic. Barriers to treatment in the emergency department can lead to missed opportunities for helping prevent overdose and relapse in individuals with opioid use disorder. The administration of buprenorphine in the emergency department can potentially lead to better treatment outcomes for these individuals.

Impulsivity and decision making in older and younger cocaine-dependent participants: A preliminary study.

BACKGROUND AND OBJECTIVES: Substance misuse is increasing in the older population, which may have differing effects on behavior compared to younger substance participants. Differences in trait and state impulsivity were assessed in younger and older cocaine-dependent participants. METHODS: Thirty-one younger cocaine-dependent participants (n = 31) and 21 older cocaine-dependent participants (n = 21) were assessed using the Barrett Impulsiveness Scale-11 and the Immediate Memory Task. RESULTS: Younger participants showed higher trait impulsivity than older participants (p =.027). However, older participants demonstrated higher state impulsivity than younger participants (p =.018). CONCLUSION: Higher state impulsivity in older cocaine participants suggests that cocaine use may have accelerating effects on the aging brain. SCIENTIFIC SIGNIFICANCE: This preliminary study adds the limited research on how cocaine use affects normal aging. Current treatments are based on younger adults, therefore the needs of older adults should be taken into consideration and studied more. (Am J Addict 2018;27:557-559).

Rapid-Response Impulsivity Predicts Depression and Posttraumatic Stress Disorder Symptomatology at 1-Year Follow-Up in Blast-Exposed Service Members.

OBJECTIVE: To determine if elevated rapid-response impulsivity after blast exposure (as a putative marker of ventral prefrontal cortex [vPFC] damage) is predictive of future elevated affective symptomatology in blast-exposed service members. DESIGN: Longitudinal design with neurocognitive testing at initial assessment and 1-year follow-up assessment of psychiatric symptomatology by telephone interview. SETTING: Veterans Administration medical centers and postdeployment assessment centers at military bases. PARTICIPANTS: Blast-exposed U.S. military personnel (N=84) ages 19 to 39 years old. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Center for Epidemiological Studies-Depression Scale (CES-D) scores, Posttraumatic Stress Disorder Checklist Version 5 (PCL-5) scores, and Alcohol Use Disorders Identification Test-C (AUDIT-C) scores at the 12-month follow-up telephone interview. RESULTS: After controlling for age and affective symptom scores reported at the initial assessment, commission errors on the Continuous Performance Test-II of the initial assessment were predictive of higher symptom scores on the CES-D and PCL-5 at follow-up, but were not predictive of AUDIT-C scores. CONCLUSIONS: Elevated rapid-response impulsivity, as a behavioral marker of reduced top-down frontocortical control, is a risk factor for elevated mood and posttraumatic stress disorder symptoms over time in blast-exposed individuals. Future longitudinal studies with predeployment neurobehavioral testing could enable attribution of this relation to blast-related vPFC damage.

Laboratory impulsivity and depression in blast-exposed military personnel with post-concussion syndrome.

In military populations, traumatic brain injury (TBI) also holds potential to increase impulsivity and impair mood regulation due to blast injury effects on ventral frontal cortex - to put military personnel at risk for suicide or substance abuse. We assessed a linkage between depression and impaired behavioral inhibition in 117 blast-exposed service members (SM) and veterans with post-concussion syndrome (PCS), where PCS was defined using a Rivermead Postconcussive Symptom Questionnaire (RPQ) modified to clarify whether each symptom worsened compared to pre-blast. Center for Epidemiological Studies-Depression Scale (CES-D) scores, PTSD Checklist 5 (PCL-5) scores, and RPQ raw subscale scores correlated positively with commission and perseverative errors on the continuous performance test II (CPT-II). In contrast, the number of RPQ symptoms ostensibly worsened post-blast did not correlate with impulsive errors on the CPT-II. These data replicate earlier findings that link increased affective symptomatology to impaired behavior inhibition in military TBI populations, but where additional effects on impulsivity from the blast itself remain equivocal.

Characterization of European Yersinia enterocolitica 1A strains using restriction fragment length polymorphism and multilocus sequence analysis.

UNLABELLED: Yersinia enterocolitica is currently divided into two subspecies: subsp. enterocolitica including highly pathogenic strains of biotype 1B and subsp. palearctica including nonpathogenic strains of biotype 1A and moderately pathogenic strains of biotypes 2-5. In this work, we characterized 162 Y. enterocolitica strains of biotype 1A and 50 strains of biotypes 2-4 isolated from human, animal and food samples by restriction fragment length polymorphism using the HindIII restriction enzyme. Phylogenetic relatedness of 20 representative Y. enterocolitica strains including 15 biotype 1A strains was further studied by the multilocus sequence analysis of four housekeeping genes (glnA, gyrB, recA and HSP60). In all the analyses, biotype 1A strains formed a separate genomic group, which differed from Y. enterocolitica subsp. enterocolitica and from the strains of biotypes 2-4 of Y. enterocolitica subsp. palearctica. Based on these results, biotype 1A strains considered nonpathogenic should not be included in subspecies palearctica containing pathogenic strains of biotypes 2-5. SIGNIFICANCE AND IMPACT OF THE STUDY: Yersinia enterocolitica strains are currently divided into six biotypes and two subspecies. Strains of biotype 1A, which are phenotypically and genotypically very heterogeneous, are classified as subspecies palearctica. In this study, European Y. enterocolitica 1A strains isolated from both human and nonhuman sources were characterized using restriction fragment length polymorphism and multilocus sequence analysis. The European biotype 1A strains formed a separate group, which differed from strains belonging to subspecies enterocolitica and palearctica. This may indicate that the current division between the two subspecies is not sufficient considering the strain diversity within Y. enterocolitica.

Effect of cocaine dependence on brain connections: clinical implications.

Cocaine dependence (CD) is associated with several cognitive deficits. Accumulating evidence, based on human and animal studies, has led to models for interpreting the neural basis of cognitive functions as interactions between functionally related brain regions. In this review, we focus on magnetic resonance imaging (MRI) studies using brain connectivity techniques as related to CD. The majority of these brain connectivity studies indicated that cocaine use is associated with altered brain connectivity between different structures, including cortical-striatal regions and default mode network. In cocaine users some of the altered brain connectivity measures are associated with behavioral performance, history of drug use, and treatment outcome. The implications of these brain connectivity findings to the treatment of CD and the pros and cons of the major brain connectivity techniques are discussed. Finally potential future directions in cocaine use disorder research using brain connectivity techniques are briefly described.

Relationship between neutrophil-to-lymphocyte ratio and impaired myocardial perfusion in cardiac syndrome X.

OBJECTIVE: Myocardial tissue perfusion is decreased in patients with cardiac syndrome X (CSX). Systemic inflammation appears to be an important contributor to the diseased microvascular network of these patients. The neutrophil-to-lymphocyte ratio (NLR) is a surrogate marker of inflammation. Accordingly, we evaluated this biomarker concerning the microvascular circulation of CSX patients. PATIENTS AND METHODS: This study included 60 consecutive patients (54.1 ± 7.8 years of age, 49 females) with CSX (typical chest pain, positive exercise stress test results, and normal coronary angiograms) and 60 consecutive age- and sex-matched control subjects. In all coronary territories, epicardial coronary flow was assessed by the Thrombolysis In Myocardial Infarction frame count (TFC) method, and myocardial tissue perfusion was assessed by the myocardial blush grade (MBG) method. Normal myocardial perfusion was accepted as an MBG score of 3 in all coronary territories. RESULTS: Patients with CSX had higher NLRs than those of control subjects (1.98 ± 0.77 vs 1.72 ± 0.55, respectively; p = 0.04). Among patients with CSX, those with impaired myocardial perfusion had higher NLRs than those with normal myocardial perfusion (2.13 ± 0.82 vs 1.71 ± 0.59, respectively; p = 0.028). There was a negative correlation between the NLR and total MBG score (p = 0.027, r = -0.29). Logistic regression analysis showed that the NLR was an independent and negative predictor of myocardial tissue perfusion (p = 0.027; Beta, -1.057; odds ratio, 2.878; 95% confidence interval, 1.129-7.335). CONCLUSIONS: Patients with CSX have high NLRs, and inflammation seems to be associated with distorted myocardial perfusion in these patients.

The prevalence and course of pulmonary hypertension and right ventricular dysfunction in patients undergoing orthotopic heart transplantation.

BACKGROUND: Pulmonary hypertension (PHT) and right ventricular (RV) dysfunction are among the commonly observed and potentially serious complications following heart transplantation. RV dysfunction is reported to occur in as much as half of these patients. In this study, the authors sought to examine the prevalence and the course of these prognostically important complications. METHODS: The records of 30 patients who had undergone orthotopic heart transplantation at our center were examined. Demographic and clinical variables were noted; RV dysfunction, pulmonary artery pressure on Doppler echocardiographic examination, and catheter findings were recorded. RESULTS: The mean age of the study population was 31.3 years. On preoperative assessment, PHT was present in 21 (70%) patients. The average value of systolic pulmonary artery pressure was 44.5 ± 5.9 mm Hg. The mean value of pulmonary vascular resistance was 3.3 ± 1.8 hybrid reference unit (HRU). RV dysfunction was detected on postoperative assessment in 17 (56.7%) patients. The mean ischemia time was 216 ± 77 minutes; in 3 cases it exceeded 5 hours but in none of the cases did it reach 6 hours. Rejection was detected in 14 (46.7%) patients. Most of the patients received inotropic agents in the early postoperative period. When compared with preoperative values, on follow up at the end of the first year, a significant decrease in pulmonary artery pressure was observed (47.4 ± 4.8 vs 38.5 ± 7.5 mm Hg; P = .03), and the ratio of patients experiencing RV dysfunction decreased to 16.6% (n = 5). CONCLUSION: The findings of this study indicate that RV dysfunction and PHT are common complications following heart transplantation and improve with appropriate management over time with monitoring.

Characteristics of Yersinia enterocolitica biotype 1A strains isolated from patients and asymptomatic carriers.

Yersinia enterocolitica biotype 1A strains are frequently isolated from the environment, foods, and animals, and also from humans with yersiniosis. There are controversial reports on the pathogenicity of biotype 1A strains. In this study, 811 fecal samples from asymptomatic humans from Switzerland were studied for the presence of Y. enterocolitica. Nine (1.1%) of the 811 samples were positive for Y. enterocolitica 1A. These strains were compared with 12 Y. enterocolitica 1A strains from Swiss patients with diarrhea isolated in the same year. Almost all (20/21) Y. enterocolitica 1A strains carried the ystB gene, seven strains carried the hreP gene, and none carried the ail, ystA, myfA, yadA, or virF genes. Most (17/21) Y. enterocolitica 1A strains belonged to two major clusters, A and B, by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Strains of cluster B were only isolated from humans with diarrhea; however, ystB and hreP genes were detected in strains from both clinical and non-clinical samples and from strains of clusters A and B. Using ribotyping, six restriction patterns among biotype 1A strains were obtained with HindIII enzyme. The most common ribotype (RT I) was found in strains isolated from humans with and without diarrhea. All biotype 1A strains had a unique NotI profile by pulsed-field gel electrophoresis (PFGE), showing a very high genetic diversity. In this study, Y. enterocolitica 1A strains from clinical and non-clinical samples could not be clearly differentiated from each other. More research is needed in order to prove that biotype 1A strains are a primary cause for human yersiniosis and not only a secondary finding.

The effect of marination on lactic acid bacteria communities in raw broiler fillet strips.

Marination with marinade containing salt, sugar, and acetic acid is commonly used in Finland to enhance the value of raw broiler meat. In this study, we investigated the effect of marination, marinade components and storage time on composition of bacterial communities in modified atmosphere-packaged (MAP) broiler fillet strips. The communities were characterized using two culture-independent methods: 16S rRNA gene fragment sequencing and terminal restriction fragment length polymorphism. In unmarinated broiler fillet strips, Lactococcus spp. and Carnobacterium spp. predominated at the early storage phase but were partially replaced by Lactobacillus spp. and Leuconostoc spp. when the chilled storage time was extended. In the marinated fillet strips, Lactobacillus spp. and Leuconostoc spp. predominated independent from the storage time. By mixing the different marinade components with broiler meat, we showed that marination changed the community composition and favored Leuconostoc spp. and Lactobacillus spp. by the combined effect of carbohydrates and acetic acid in marinade. Marination increased the maximum level of lactic acid bacteria in broiler meat and enhanced CO(2) production and acidification of meat during the chilled storage. Accumulation of CO(2) in package head-space due to the enhanced growth of Leuconostoc spp. in marinated meat may lead to bulging of packages, which is a spoilage defect frequently associated with marinated and MAP raw broiler preparations in Finland.

Comparison of microbial communities in marinated and unmarinated broiler meat by metagenomics.

Most raw poultry sold in Finland at the retail level is mixed with marinades containing oil, sugar, spices and acetic acid and packaged under modified atmosphere. Premature spoilage of marinated poultry preparations has been observed and associated with high levels of Leuconostoc spp. in meat. In this study we investigated whether marination of broiler fillet strips increased the proportion of Leuconostoc spp. in the microbial communities. To obtain a comprehensive view of the microbiota, we sequenced total DNA and 16S rRNA gene amplicons from the microbial communities. The lactic acid bacterial communities were characterized also by identification of colonies. The results showed that marinade increased the proportions of the spoilage-associated Leuconostoc gasicomitatum in the communities as well as the proportions of Leuconostoc gelidum and Lactobacillus spp. The proportions of Carnobacterium, Vagococcus, Brochothrix thrermosphacta, Clostridium, Enterobacteriaceae and Vibrio were diminished in marinated meat. Analysis of 16S rRNA gene amplicons resulted in 312 and 284 operational taxonomical units (dissimilarity 0.03) in unmarinated and marinated meat, respectively, indicating that the meat communities were more diverse than hitherto shown. Metagenomic analysis revealed a number of bacterial taxa that have not been associated with late shelf-life meat before, including Vagococcus and Vibrio that belonged to the predominating part of the microbial community in unmarinated meat. According to the functional analysis of the metagenomes, the communities in both marinated and unmarinated poultry were characterized by high proportions (15.6% or 17.9%) of genes involved in carbohydrate metabolism.

High number of Yersinia enterocolitica 4/O:3 in cold-stored modified atmosphere-packed pig cheek meat.

Yersinia enterocolitica is a psychrotrophic, facultative anaerobic zoonotic bacterium belonging to family Enterobacteriaceae and it can be transmitted from pigs to humans through pork. The growth of bacteria belonging to Enterobacteriaceae and aerobic spoilage bacteria is usually effectively restricted by 20% or more CO(2) enriched atmosphere at refrigerated temperatures. In this study, 40 samples of meat strips from pig cheek (musculus masseter) and 40 samples from hind leg (m. semimembranosus) muscles were packaged in modified atmosphere (MA) (30% CO(2)/70% O(2)) and stored at 6°C for 12d. Twenty naturally contaminated samples per muscle type were studied on days 1 and 13. Violet red bile glucose (VRBG) and de Man Rogosa Sharpe (MRS) agar plates were used for enumeration of Enterobacteriaceae including Y. enterocolitica and lactic acid bacteria, respectively. During the 12-d storage at 6°C in MA, the mean number of bacteria on pork strips of cheek meat was increasing from 1.6 to 4.5 log cfu/g and from 3.1 to 7.2 log cfu/g on VRBG and MRS agar plates, respectively. Most of the oxidase-negative isolates on VRBG plates, which were isolated from the cheek meat samples after 12-d cold storage in MA, were identified as Y. enterocolitica 4/O:3. The mean number of this pathogen was 4.1 log cfu/g varying between 2.3 and 5.4 log cfu/g. The pH of the cheek meat and leg meat was measured on days 1 and 13, and it remained high (pH>6) in most cheek meat samples during the storage. No Y. enterocolitica 4/O:3 was isolated from meat strips of hind leg. This study shows that cheek meat of slaughter pigs is contaminated with Y. enterocolitica 4/O:3 and that this pathogen can grow well on raw pork packaged in MA at 6°C even in the presence of high number of lactic acid bacteria.

Comparison of tissue Doppler echocardiography parameters in patients with end-stage renal disease and renal transplant recipients.

BACKGROUND: Tissue Doppler echocardiography has been introduced as a useful tool to assess systolic myocardial function. In this study we sought to compare patients with end-stage renal disease (ESRD), with renal transplantations and control subjects with regard to tissue Doppler parameters. METHODS: Thirty recipients with functional grafts of overall mean age 36 +/- 7 years included 24 men. An equal number of patients with ESRD of overall mean age 35 +/- 7 years included 20 men. A third cohort was comprised of 20 age- and gender matched control subjects. Tissue Doppler imaging from the septal and lateral mitral annulus of the left ventricle and free wall of the right ventricle was performed from a 4-chamber view. RESULTS: Mean systolic and diastolic blood pressures were similar among the groups during imaging. Peak systolic velocity (S wave) at the septal annulus was similar in control subjects and recipients. S waves were significantly lower among ESRD patients compared with recipients (10.3 +/- 2.1 vs 12.0 +/- 2.5 cm/s, P = .04, respectively). Isovolumic contraction velocity of the septum and the right ventricular wall were significantly lower in ESRD patients than recipients or controls: 10.2 +/- 2.6 vs 12.5 +/- 2.8 vs 11.4 +/- 1.8 cm/s for septal wall (P = .008) and 13.9 +/- 3.6 vs 17.9 +/- 5.1 vs 16.8 +/- 5.8, for right ventricle (P = .01). CONCLUSION: Systolic indices of tissue Doppler echocardiography in recipients demonstrated similar values as control subjects and increased values compared with ESRD patients. These results suggested improvement in systolic myocardial function following renal transplantation.

Surgery-related complications in cardiac transplantation patients.

OBJECTIVE: The surgical techniques was first described by Lower and Shumway for cardiac transplantation have not changed for many years; they are still being commonly used worldwide despite recently presented alternatives. We sought to evaluate the surgical complications among our cardiac transplantation patients in whom we performed the standard technique. PATIENTS AND METHODS: The standard biatrial anastomosis technique was used in 13 patients who have a mean follow-up of 18.6 (1 to 38) months. During the follow-up, echocardiographic assessment was performed to evaluate left and right atrial diameters, tricuspid and mitral valve regurgitation, interatrial septum, and suture lines. Elecotrocardiograms were evaluated for arryhthmia and pacemaker requirements in the midterm. RESULTS: The mean left and right atrial diameters were measured as 40.5 (32 to 57) x 66.6 (48 to 78) and 37.9 (32 to 43) x 56.3 (48 to 69) mm, respectively. The jet area was calculated at less than 5 cm(2) for mitral and tricuspid valve regurgitation, which can be defined as "mild" regurgitation. There was no increase in the degree of regurgitation of both atrioventricular valves during the follow-up period. In one patient, a thrombus was detected in the suture line; there was a nonsignificant left to right shunt in another patient. A temporary pacemaker was indicated in two patients. Atrial fibrillation was detected in three patients, who responded to medical therapy. During the follow-up atrial fibrillation developed in one patient. CONCLUSION: The cardiac transplantation operation using the standard technique may result in atrial dysfuntion due to deformation of atrial integrity and geometry. However, when we evaluated our results, we concluded that the standard surgical technique was a safe, simple, effective, and feasible method.

Lipid profiles of patients with a transplanted heart before and after the operation.

BACKGROUND: Graft coronary artery disease, a serious problem after orthotopic heart transplantation (OHT), has multifactorial etiologies with dyslipidemia as one of the major risk factors. In this study we examined lipid profiles and drug therapy of our patients before and after OHT. METHODS: Thirteen patients who underwent OHT at our center were enrolled in the study. We noted the patients' clinical and demographic data and current medications as well as pre- and postoperative lipid values. RESULTS: The mean age of the study group was 32.0 +/- 13.2 years with three women. Compared to the preoperative values, significant increases were detected in the mean levels of low-density lipoprotein (LDL) (81.3 +/- 29.1 vs 103.5 +/- 22.2 mg/dL; P = .03) and total cholesterol (142.0 +/- 58.5 vs 184.0 +/- 37.8 mg/dL; P = .02), while triglyceride (113.5 +/- 67.3 vs 137.0 +/- 69.9 mg/dL; P = .1) and high-density lipoprotein (42.7 +/- 10.2 vs 48.7 +/- 14.4 mg/dL; P = .2) levels did not change significantly at 2 to 3 months postoperatively. On follow-up eight patients were prescribed a statin (atorvastatin in all), one of whom was on ezetimibe in addition to statin and one, fenofibrate. The patients tolerated lipid-lowering agents well; no significant side effect was noted. CONCLUSION: These findings demonstrated increased lipid values, mainly in total cholesterol and LDL levels, after OHT. Regarding the importance of dyslipidemia as a major atherosclerotic risk factor, we believe that statins in the absence of a contraindication should be part of the treatment protocol in patients with a transplanted heart.

The effects of chronic carvedilol therapy on QT dispersion in patients with congestive heart failure.

BACKGROUND: Carvedilol therapy reduces mortality from sudden cardiac death and progressive pump failure in congestive heart failure (CHF). However, the effect(s) of carvedilol on ventricular repolarization characteristics is unclear. AIM: The aim of the study was to investigate the effects of chronic carvedilol therapy on ventricular repolarization characteristics as assessed by QT dispersion (QTd) in patients with CHF. METHOD: Nineteen patients (age 53+/-12 years; 16 male, three female) with CHF (eight ischemic, 11 non-ischemic dilated cardiomyopathy) were prospectively included in the study. Carvedilol was administered in addition to standard therapy for CHF at a dose of 3.125 mg bid and uptitrated biweekly to the maximum tolerated dose. From standard 12-lead electrocardiograms the maximum and minimum QT intervals (QTmax, QTmin), QTd, corrected QT intervals (QTcmax, QTcmin) and corrected QTd (QTcd) values were calculated at baseline, after the 2nd and the 16th month of carvedilol therapy. RESULTS: A significant reduction was noted in the QTd and QTcd values with carvedilol therapy after the 16th month (QTd: 81+/-22 ms vs. 40+/-4.3 ms P<0.001; QTcd: 91+/-25 ms vs. 51+/-7 ms P<0.001), but not after the 2nd month (P>0.05). The resting heart rate was also significantly reduced after a 16-month course of carvedilol therapy (78+/-13 bpm vs. 66+/-15 bpm, P<0.05). Carvedilol therapy did not alter QTmax and QTcmax intervals (P>0.05), however, QT min and QTcmin significantly increased with carvedilol at the 16th month (P<0.001 and P<0.01, respectively). CONCLUSION: Long-term carvedilol therapy was associated with a reduction in QTd, an effect that might contribute to the favorable effects of carvedilol in reducing sudden cardiac death in CHF.

Soy protein diet significantly improves endothelial function and lipid parameters.

BACKGROUND: Replacement of animal protein with soy protein in the diet is associated with decreased cholesterol levels. However, the effects of soy protein diet on endothelial function are not well known. HYPOTHESIS: The aim of the study was to investigate the effects of soy protein diet on plasma lipids and endothelial function parameters assessed by two different methods. METHODS: Twenty hypercholesterolemic, nonsmoker male patients (age 50.1+/-11.8 years), with a normal body mass index, were included. After calculating their daily requirements, a diet with 25-30% of energy from fats. 10-12% from proteins, and the rest from carbohydrates was instituted. Sixty percent of the animal source proteins of the diet were substituted by soy. The anthropometric measures, lipid parameters, and endothelial functions of the subjects were assessed at baseline and 6 weeks after soy protein diet. Flow-mediated endothelium-dependent dilatation (EDD) and plasma thrombomodulin (TM) levels were evaluated as endothelial function parameters. RESULTS: After diet, plasma total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, and triglyceride levels decreased significantly (p <0.001, p < 0.001, p = 0.039, and p = 0.001, respectively). The mean plasma TM levels were also significantly reduced with diet (p = 0.004). Studies of the brachial artery indicated a borderline dilatation in baseline brachial artery diameter (p = 0.05), however the diameter at reactive hyperemia was significantly larger after diet (p<0.001), resulting in a significant improvement of EDD (p = 0.002). CONCLUSION: Soy protein diet significantly improves plasma lipid profile in patients with hypercholesterolemia. Furthermore, the endothelial function, as judged by two different methods (EDD and plasma TM levels), also improves with soy protein diet.

P wave dispersion on 12-lead electrocardiography in patients with paroxysmal atrial fibrillation.

The prolongation of intraatrial and interatrial conduction time and the inhomogeneous propagation of sinus impulses have been shown in patients with atrial fibrillation. Recently P wave dispersion (PWD), which is believed to reflect inhomogeneous atrial conduction, has been proposed as being useful for the prediction of paroxysmal atrial fibrillation (PAF). Ninety consecutive patients (46 men, 44 women; aged 55 +/- 13 years) with a history of idiopathic PAF and 70 healthy subjects (42 men, 28 women; mean age 53 +/- 14 years) were studied. The P wave duration was calculated in all 12 leads of the surface ECG. The difference between the maximum and minimum P wave duration was calculated and this difference was defined as P wave dispersion (PWD = Pmax-Pmin). All patients and controls were also evaluated by echocardiography to measure the left atrial diameter and left ventricular ejection fraction (LVEF). There was no difference between patients and controls in gender (P = 0.26), age (P = 0.12), LVEF (66 +/- 4% vs 67 +/- 5%, P = 0.8) and left atrial diameter (36 +/- 4 mm vs 34 +/- 6 mm, P = 0.13). P maximum duration was found to be significantly higher in patients with a history of PAF (116 +/- 17 ms) than controls (101 +/- 11 ms, P < 0.001). P wave dispersion was also significantly higher in patients than in controls (44 +/- 15 ms vs 27 +/- 10 ms, P < 0.001). There was a weak correlation between age and P wave dispersion (r = 0.27, P < 0.001). A P maximum value of 106 ms separated patients with PAF from control subjects with a sensitivity of 83%, a specificity of 72%, and a positive predictive accuracy of 79%. A P wave dispersion value of 36 ms separated patients from control subjects with a sensitivity of 77%, a specificity of 82%, and a positive predictive accuracy of 85%. In conclusion, P maximum duration and P wave dispersion calculated on a standard surface ECG are simple ECG markers that could be used to identify the patients with idiopathic paroxysmal atrial fibrillation.