Homocysteine-Lowering Therapy and Early Progression of Transplant Vasculopathy: A Prospective, Randomized, IVUS-Based Study

Although observational studies suggest that hyperhomocysteinemia may be a risk factor for coronary allograft vasculopathy (CAV), prospective data on homocysteine-lowering interventions and CAV development are lacking. We, therefore, randomized 44 de novo heart transplant (HT) recipients to 15 mg/day of 5-methyl-tetrahydrofolate (n=22), or standard therapy (control group, n=22) to investigate the effect of homocysteine lowering on the change in coronary intimal hyperplasia during the first 12 months after transplant, as detected by intra-vascular ultrasound (IVUS). Although 12 months after HT, homocysteinemia was lower in folate-treated patients (p<0.001), coronary intimal area increased similarly in the two groups (p>0.4). Conversely, hypercholesterolemia and cytomegalovirus infection were both associated with increased intimal hyperplasia (p<0.04), independently from folate intake. Sub-group analysis revealed that folate therapy reduced intimal hyperplasia in patients with hyperhomocysteinemia before randomization (n=19; p=0.02), but increased intimal hyperplasia in patients with normal homocysteine plasma concentrations (p=0.02). This bimodal effect of folate therapy persisted significantly after adjusting for cytomegalovirus infection and hypercholesterolemia. Despite effective in prevent hyperhomocysteinemia after heart transplantation, folate therapy does not seem to affect early CAV onset. However, sub-group analysis suggests that folate therapy may delay CAV development only in patients with baseline hyperhomocysteinemia, while may favor CAV progression in recipients with normal baseline homocysteinemia.     

Sensory retraining is key to biofeedback therapy for formed stool fecal incontinence

OBJECTIVES: Biofeedback is a nonsurgical treatment that reportedly produces good results in 65-75% of fecally incontinent patients. However, previous studies have not ruled out nonspecific treatment effects. It is also unknown whether biofeedback works primarily by improving the strength of the striated pelvic floor muscles or by improving the rectal perception. We aimed to 1) evaluate the efficacy of biofeedback in formed-stool fecal incontinence, 2) assess the relative contribution of sensory and strength retraining to biofeedback outcomes, and 3) identify patient characteristics that predict a good response to treatment. METHODS: Twenty-four patients with frequent (at least once a week) solid-stool incontinence were provided with three to four biofeedback sessions. They were taught to squeeze in response to progressively weaker rectal distentions. Patients were re-evaluated by anorectal manometry and symptom diary 3 months after completing training and by diary and interview 6-12 months after training. RESULTS: Seventeen (71%) were classified responders; 13 became continent and four reduced incontinence frequency by at least 75%. Clinical improvements were maintained at 12-month follow-up. At 3-month follow-up, responders had significantly lower thresholds for perception of rectal distention and for sphincter contraction, but squeeze pressures did not significantly differ from those of nonresponders. Baseline measures that predicted a favorable response were sensory threshold (50 ml or less), urge threshold (100 ml or less), lower threshold for sphincter contraction, and lower threshold for the rectoanal inhibitory reflex; neither anal squeeze pressure nor severity of incontinence predicted treatment outcome. CONCLUSIONS: In solid-stool fecal incontinence biofeedback training effects are robust and seem not to be explained by expectancy or nonspecific treatment effect. Sensory retraining appears to be more relevant than strength training to the success of biofeedback.     

Automated characterization of multiple alpha peaks in multi-site electroencephalograms

The identification of alpha rhythm in the human electroencephalogram (EEG) is generally a laborious task involving visual inspection of the spectrum. Moreover the occurrence of multiple alpha rhythms is often overlooked. This paper seeks to automate the process of identifying alpha peaks and quantifying their frequency, amplitude and width as a function of position on the scalp. Experimental EEG was fitted with parameterized spectra spanning the alpha range, with results categorized by multi-site criteria into three distinct classes: no distinguishable alpha peak, a single alpha peak, and two alpha peaks. The technique avoids visual bias, integrates spatial information, and is automated. We show that multiple alpha peaks are a common feature of many spectra.     

Recognition of patients with cardiovascular disease by artificial neural networks

BACKGROUND: Artificial neural networks (ANNs) are computer algorithms inspired by the highly interactive processing of the human brain. When exposed to complex data sets, ANNs can learn the mechanisms that correlate different variables and perform complex classification tasks. AIMS: A database, of 949 patients and 54 variables, was analysed to evaluate the capacity of ANNs to recognise patients with (VE+, n = 196) or without (VE-, n = 753) a history of vascular events on the basis of vascular risk factors (VRFs), carotid ultrasound variables (UVs) or both. METHOD: The performance of ANN was assessed by calculating the percentage of correct identifications of VE+ and VE- patients (sensitivity and specificity, respectively) and the prediction accuracy (weighted mean between sensitivity and specificity). RESULTS: The results showed that ANNs can be trained to identify VE+ and VE- subjects more accurately than discriminant analyses. When VRFs and UVs were used as input variables, the prediction accuracies of the ANN providing the best results were 80.8% and 79.2%, respectively. The addition of gender, age, weight, height and body mass index to UVs increased accuracy of prediction to 83.0%. When the ANNs were allowed to choose the relevant input data automatically (I.S. system-Semeion), 37 variables were selected among 54, five of which were UVs. Using this set of variables as input data, the performance of the ANNs in the classification task reached a prediction accuracy of 85.0%. with the 92.0% correct classification of VE+ patients. CONCLUSIONS: Artificial neural network technology is highly promising in the development of accurate diagnostic tools designed to recognize patients at high risk of cardiovascular diseases.     

Chronic hepatitis B in children after e antigen seroclearance: final report of a 29-year longitudinal study

Chronic hepatitis B is usually a benign disease in Caucasian children; however, the long-term prognosis remains unsettled. This report describes the results of a 29-year longitudinal study including 99 white children with chronic hepatitis B, mainly acquired horizontally: 91 were hepatitis B e antigen (HBeAg) positive (4 had cirrhosis), and 8 were HBeAg negative at presentation. Of the 91 HBeAg-positive children, 89 underwent HBeAg seroconversion after a mean period of 5.2 +/- 4.0 years and were included in the study. Of the 85 children without cirrhosis, one had HBeAg-negative hepatitis and the other 84 became inactive carriers. During a mean follow-up of 14.5 +/- 6.1 years after HBeAg seroclearance, 4 carriers experienced reactivation, and 3 of them had HBeAg-negative hepatitis at the last follow-up. Of the 8 initially HBeAg-negative children, 2 had HBeAg-negative hepatitis, and 6 were inactive carriers. Of the 4 children with cirrhosis, 2 had hepatocellular carcinoma (HCC) and remained alive and 2 lost the histological features of cirrhosis in adulthood. Two patients with HBeAg-negative hepatitis and 1 with cirrhosis had experienced drug abuse. At the end of follow-up, 15 of the 89 initially HBeAg-positive patients and 2 of 8 initially HBeAg-negative children had cleared hepatitis B surface antigen. In conclusion, the overall prognosis for chronic hepatitis B in horizontally infected Caucasian children is favorable; however, some patients progress to HCC and HBeAg-negative hepatitis. Long-term monitoring is important, as is counseling on cofactors of liver damage, such as alcohol and drug abuse.     

BOLD responses to stimuli: dependence on frequency, stimulus form, amplitude, and repetition rate

A quantitative theory is developed for the relationship between stimulus and the resulting blood oxygen level-dependent (BOLD) functional MRI signal. The relationship of stimuli to neuronal activity during evoked responses is inferred from recent physiology-based quantitative modeling of evoked response potentials (ERPs). A hemodynamic model is then used to calculate the BOLD response to neuronal activity having the form of an impulse, a sinusoid, or an ERP-like damped sinusoid. Using the resulting equations, the BOLD response is analyzed for different forms, frequencies, and amplitudes of stimuli, in contrast with previous research, which has mostly concentrated on sustained stimuli. The BOLD frequency response is found to be closely linear in the parameter ranges of interest, with the form of a low-pass filter with a weak resonance at approximately 0.07 Hz. An improved BOLD impulse response is systematically obtained which includes initial dip and post-stimulus undershoot for some parameter ranges. It is found that the BOLD response depends strongly on the precise temporal course of the evoked neuronal activity, not just its peak value or typical amplitude. Indeed, for short stimuli, the linear BOLD response is closely proportional to the time-integrated activity change evoked by the stimulus, regardless of amplitude. It is concluded that there can be widely differing proportionalities between BOLD and peak activity, that this is the likely reason for the low level of correspondence seen experimentally between ERP sources and BOLD measurements and that non-BOLD measurements, such as ERPs, can be used to correct for this effect to obtain improved activity estimates. Finally, stimulus sequences that optimize the signal-to-noise ratio in event-related BOLD fMRI (efMRI) experiments are derived using the hemodynamic transfer function.     

The use of echocardiography for the non-invasive evaluation of coronary artery disease

In the Western world, there are now millions of patients who undergo clinical procedures that evaluate coronary artery status each year. Methods span from direct imaging using angiography, computerized tomography, to nuclear magnetic imaging as well as to functional studies, such as positron emission tomography. These techniques have provided significant information to physicians, but there is still need for an improved accessibility. Angiographic methods are expensive and expose the patient to significant amounts of radiation, undesirable in younger patients. Among the novel technologies for coronary diagnostics, transthoracic echocardiography (TTE) of coronary arteries has provided an important alternative, particularly in everyday practice. Diagnostic arterial TTE can allow determination of the coronary wall lumen in at least three major coronary segments (left main [LM], left arterial descending [LAD] and right coronary artery [RCA]). Coronary wall thickness using the LAD has been preliminarily shown to be related to the risk of coronary events. Since it is well ascertained that coronary lesions found in any location indicate that at least 80% of the coronary tree is affected, this is very important clinical information. Evaluation of coronary status by TTE is a novel technology providing important information in ischemic syndromes, in cases of coronary malformations and other coronary diseases.

• KEY MESSAGES

• Coronary evaluation can be carried out by a variety of both invasive and non-invasive methods, many requiring radiation exposure or patient immobility.

• Transthoracic echocardiography (TTE) of the coronaries can, in particular, evaluate the coronary wall thickness, and this may be directly related to the coronary disease risk.

• TTE is a useful method for the monitoring of coronary flow reserve and can allow the detection of coronary malformations.

     

Personality disorders and the five-factor model among French speakers in Africa and europe

Objective: To describe the relation between personality disorders (PDs) and the Five-Factor Model (FFM)-a dimensional model describing normal personality traits known for its invariance across cultures-in 2 different cultural settings. Several authors have suggested that PDs may be more accurately described using a dimensional model instead of a categorical one. Method: Subjects from 9 French-speaking African countries (n = 2014) and from Switzerland (n = 697) completed both the French version of the International Personality Disorder Examination screening questionnaire, assessing the 10 DSM-IV PDs, and the French version of the Revised NEO Personality Inventory, assessing the 5 domains and 30 facets of the FFM. Results: Correlations between PDs and the 5 domains of the FFM were similar in both samples. For example, neuroticism was highly correlated with borderline, avoidant, and dependent PDs in both Africa and Switzerland. The total rank-order correlation (rho) between the 2 correlation matrices was very high (rho = 0.93) and significant (P < 0.001), as were the rhos for all domains of the FFM and all PDs, except paranoid and dependent PDs. However, the rhos for PDs across facet scales were all highly significant (P < 0.001). Moreover, 80% of Widiger and colleagues' predictions and 70% of Lynam and Widiger's prototypes, concerning the relation between PDs and the FFM, were confirmed in both samples. Conclusions: The relation between PDs and the FFM was stable in 2 samples separated by a great cultural distance. These results suggest that a dimensional approach and in particular the FFM may be useful for describing PDs in various cultural settings.