Multielectron dissociative ionization of methane and formaldehyde molecules with optimally tailored intense femtosecond laser pulses.

The multielectron dissociative ionization of CH4 and CH2O molecules has been investigated using optimum convolution of different dual tailored short laser pulses. Based on three dimensional molecular dynamics simulations and TDDFT approach, the dissociation probability is enhanced by designing the dual chirped-chirped laser pulses and chirped-ordinary laser pulses for formaldehyde molecule. However, it is interesting to notice that the sensitivity of enhanced dissociation probability into different tailored laser pulses is not significant for methane molecule. In this presented modifications, time variation of bond length, velocity, time dependent electron localization function and evolution of the efficient occupation states are presented to analyze the time evolution of molecular dynamics. This work is proved to be a potential way to reduce the controlling costs with a currently available pulse shaping technology.

Selective photo-dissociative ionization of methane molecule with TDDFT study.

Three dimensional calculation of control dynamics for finding the optimized laser filed is formulated using an iterative method and time-dependent density functional approach. An appropriate laser pulse is designed to control the desired products in the dissociation of methane molecule. The tailored laser pulse profile, eigenstate distributions and evolution of the efficient occupation numbers are predicted and exact energy levels of this five-atomic molecule is obtained. Dissociation rates of up to 78%, 80%, 90%, and 82% for CH2+, CH+, C+ and C++ are achieved. Based on the present approach one can reduce the controlling costs.

Hippocampal volume change relates to clinical outcome in childhood-onset schizophrenia.

BACKGROUND: Fixed hippocampal volume reductions and shape abnormalities are established findings in schizophrenia, but the relationship between hippocampal volume change and clinical outcome has been relatively unexplored in schizophrenia and other psychotic disorders. In light of recent findings correlating hippocampal volume change and clinical outcome in first-episode psychotic adults, we hypothesized that fewer decreases in hippocampal volume would be associated with better functional outcome and fewer psychotic symptoms in our rare and chronically ill population of childhood-onset schizophrenia (COS) patients. METHOD: We prospectively obtained 114 structural brain magnetic resonance images (MRIs) from 27 COS subjects, each with three or more scans between the ages of 10 and 30 years. Change in hippocampal volume, measured by fit slope and percentage change, was regressed against clinical ratings (Children's Global Assessment Scale, Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms) at last scan (controlling for sex, time between scans and total intracranial volume). RESULTS: Fewer negative symptoms were associated with less hippocampal volume decrease (fit slope: p = 0.0003, and percentage change: p = 0.005) while positive symptoms were not related to hippocampal change. There was also a relationship between improved clinical global functioning and maintained hippocampal volumes (fit slope: p = 0.025, and percentage change: p = 0.043). CONCLUSIONS: These results suggest that abnormal hippocampal development in schizophrenia can be linked to global functioning and negative symptoms. The hippocampus can be considered a potential treatment target for future therapies.

High rate of disease-related copy number variations in childhood onset schizophrenia.

Copy number variants (CNVs) are risk factors in neurodevelopmental disorders, including autism, epilepsy, intellectual disability (ID) and schizophrenia. Childhood onset schizophrenia (COS), defined as onset before the age of 13 years, is a rare and severe form of the disorder, with more striking array of prepsychotic developmental disorders and abnormalities in brain development. Because of the well-known phenotypic variability associated with pathogenic CNVs, we conducted whole genome genotyping to detect CNVs and then focused on a group of 46 rare CNVs that had well-documented risk for adult onset schizophrenia (AOS), autism, epilepsy and/or ID. We evaluated 126 COS probands, 69 of which also had a healthy full sibling. When COS probands were compared with their matched related controls, significantly more affected individuals carried disease-related CNVs (P=0.017). Moreover, COS probands showed a higher rate than that found in AOS probands (P<0.0001). A total of 15 (11.9%) subjects exhibited at least one such CNV and four of these subjects (26.7%) had two. Five of 15 (4.0% of the sample) had a 2.5-3 Mb deletion mapping to 22q11.2, a rate higher than that reported for adult onset (0.3-1%) (P<0.001) or autism spectrum disorder and, indeed, the highest rate reported for any clinical population to date. For one COS subject, a duplication found at 22q13.3 had previously only been associated with autism, and for four patients CNVs at 8q11.2, 10q22.3, 16p11.2 and 17q21.3 had only previously been associated with ID. Taken together, these findings support the well-known pleiotropic effects of these CNVs suggesting shared abnormalities early in brain development. Clinically, broad CNV-based population screening is needed to assess their overall clinical burden.

PAI-I 4G/5G polymorphism and sudden cardiac death in patients with coronary artery disease.

UNLABELLED: The 4G/5G polymorphism of the plasminogen activator inhibitor type I (PAI-I) gene is involved in coronary artery disease (CAD), with the highest risk in 4G/4G homozygotes. The role of PAI-I polymorphism in patients suffering from CAD and history of sudden cardiac death (SCD) has not been addressed yet. We studied the frequency distribution of the PAI-I gene to test the hypothesis that the 4G/4G genotype favors myocardial ischemia and, even in the absence of acute infarction, promotes SCD in patients with CAD. METHODS: The PAI-I 4G/5G genotypes and PAI-I antigen plasma levels were determined in 97 patients with CAD and a history of SCD treated with an implantable cardioverter defibrillator (ICD) (defibrillator group) comparing to 113 patients with CAD but no history of SCD (control group). RESULTS: The defibrillator group consisted of significantly more 4G/4G homozygotes and higher PAI-I levels than the control group (44% vs. 24%, 173+/-41 vs. 144+/-49 ng/ml; P<.01). The carriers of 4G allele had a significantly higher risk for SCD (odds ratio (OR) 1.9) with the highest risk in the 4G/4G genotype (OR 3.6, P<.01). CONCLUSION: These results suggest that the PAI-I 4G/4G genotype is associated with SCD in patients suffering from CAD.

Platelet glycoprotein Ia gene dimorphism alpha2-807 in malignant arrhythmia in coronary artery disease.

It has been shown recently that the variable expression of the platelet collagen receptor integrin alpha2beta1 predisposes to thrombotic risk on the one hand and hemorrhagic risk on the other hand. The level of expression of the integrin alpha2beta1 is genetically controlled and associated with the alpha2-807 dimorphism. The expression level of this platelet collagen receptor may play a central role in the rapidly evolving coronary artery lesions that lead to malignant arrhythmia and sudden cardiac death. We studied allelic frequencies of the alpha2-807 dimorphism for their relation as a risk factor for malignant arrhythmia in a well-defined subgroup of patients with coronary artery disease. We compared allelic frequencies (by sequence specific primer polymerase chain reaction) of the dimorphism that is associated with integrin alpha2beta1 levels in 94 Caucasoid survivors of sudden cardiac death with a matched group of 106 patients with coronary artery disease without sudden cardiac death. Gene frequencies in the patient groups did not differ and were similar to those in the general population represented by 217 healthy individuals. There was no overrepresentation of an allele in any group. The inherited dimorphism that is associated with the levels of platelet integrin alpha2beta1 is not associated with malignant arrhythmia in coronary artery disease patients.

Local anaesthesia versus general anaesthesia for cardioverter-defibrillator implantation.

AIMS: Cardioverter-defibrillators are conventionally implanted under general anaesthesia. However, implantation under conscious sedation is being increasingly used. It has been shown that cardioverter-defibrillators can be implanted in a more pacemaker-like approach: under local anaesthesia for the surgical procedure, and with mild sedation for defibrillation threshold testing only. The aim of the present study was to compare local and general anaesthesia in defibrillation threshold testing and implantation of cardioverter-defibrillators. METHODS AND RESULTS: Forty patients were assigned to two groups: in the first 20 consecutive patients the cardioverter-defibrillator was implanted under general anaesthesia (GA), and in the subsequent 20 patients under local anaesthesia (LA). There was no significant difference between the two groups in regard of age, body weight, underlying disease, left ventricular ejection fraction, and NYHA classification. The defibrillation threshold was 13.7 +/- 5.5 J under local anaesthesia versus 10.7 +/- 4.7 J under general anaesthesia (n.s.). For defibrillation threshold testing 7.9 +/- 3.6 shocks had to be applied in patients under general anaesthesia versus 6.2 +/- 1.3 shocks under local anaesthesia (n.s.). Mean heart rate, arterial oxygen saturation and mean arterial blood pressure remained stable throughout defibrillation threshold testing, irrespective of the type of anaesthesia used. The duration of the surgical procedure was 62 +/- 16 min under GA and 60 +/- 14 min under LA (n.s.), however, the entire implantation procedure was significantly longer in patients under general anaesthesia than in those under local anaesthesia (124 +/- 24 min and 97 +/- 22 min, respectively, p < 0.005). There were no complications in either group and the procedure was well tolerated. With the use of local anaesthesia the cost of anaesthesia were reduced by 72%. CONCLUSION: Local anaesthesia in combination with mild sedation is as safe and well tolerated as general anaesthesia in cardioverter-defibrillator implantation. Lidocaine used for local anaesthesia does not adversely affect the defibrillation threshold. Device implantation in a pacemaker-like approach results in a significant reduction in total procedure time and costs, and facilitates scheduling of the procedure.

Angiotensin-converting enzyme and angiotensin II receptor 1 polymorphism in coronary disease and malignant ventricular arrhythmias.

OBJECTIVES: It has been reported that patients carrying the angiotensin-converting enzyme (ACE) deletion DD genotype with the angiotensin II type 1 (AT1) C allele are at increased risk for myocardial infarction. The frequency distribution of the ACE and AT1 receptor gene polymorphism and their possible relation regarding malignant ventricular arrhythmias in patients with coronary artery disease (CAD) and left ventricular dysfunction was determined. METHODS: The ACE I/D and AT1 A/C polymorphisms (using polymerase chain reaction) in 100 Caucasian patients suffering from CAD with a history of malignant ventricular arrhythmias treated with an implantable cardioverter defibrillator (ICD group) was compared to 127 age-matched Caucasian patients with CAD and no history of malignant ventricular arrhythmias (control group). All patients had reduced left ventricular ejection fraction of < 40% and were comparable regarding sex distribution, body mass index, ACE-inhibitor treatment, lipid status and duration of CAD. RESULTS: The prevalence of DD/CC in the ICD group was significantly higher (19% versus 10%, p < 0.0001). The risk for malignant ventricular arrhythmias was associated with the combination of ACE D and AT1 C alleles (odds-ratio: 2.4, 95% confidence interval 1.41 to 3.94, p < 0.001). The distribution of ACE and AT1 genotypes was not different between the two group. CONCLUSIONS: Patients with coronary artery disease and left ventricular dysfunction carrying ACE D and AT1 C alleles are at increased risk for development of malignant ventricular arrhythmias. Because of available pharmacological inhibitors, these results may have clinical implications for the prevention of sudden cardiac death.

Predictors of outcome in patients with implantable cardioverter defibrillators.

UNLABELLED: This study determined the impact of clinical characteristics on shock occurrence and survival in patients with implantable cardioverter-defibrillator (ICD). METHODS AND RESULTS: During a follow-up of 27 +/- 18 months, the actuarial incidence of appropriate shocks in 200 consecutive patients was 18, 36 and 72% at 1, 3, and 5 years, respectively. Coronary artery disease was the only significant predictor for shock occurrence (relative risk 1.32, p = 0.03). The actuarial incidence of total mortality was 10, 17 and 33% at 1, 3, and 5 years, respectively. The most powerful predictors for total mortality were: New York Heart Association functional class (NYHA) III (relative risk 4.8, p = 0.001) and a history of congestive cardiac failure (relative risk 3.6, p = 0.01). CONCLUSION: During long-term follow-up, the majority of patients receive appropriate shocks. No strong predictors for shock occurrence can be identified from the data analyzed. A history of congestive cardiac failure and the NYHA III are the most powerful predictors for total mortality. These clinical factors may provide valuable criteria to identify patients who will benefit from the implantation of ICD.

Effects of lidocaine, ajmaline, and diltiazem on ventricular defibrillation energy requirements in isolated rabbit heart.

The majority of patients with implanted cardioverter defibrillators (ICD) require antiarrhythmic (AR) drugs. ARs may increase defibrillation energy requirements. This study investigated the effects of lidocaine, ajmaline, and diltiazem on ventricular defibrillation energy needs. In 24 isolated rabbit hearts, the 50 and 80% successful defibrillation energy (ED50, ED80) was calculated in four phases: predrug baseline condition (phase 1), and phases 2, 3, and 4 with increasing concentrations of lidocaine, ajmaline, diltiazem (n = 18). Control experiments (n = 6) with only Tyrode's solution infusion indicated that the preparation was stable over time. Defibrillation energy requirements significantly (p < 0.05) increased with all ARs. Low, medium, and high lidocaine concentrations increased ED50 and ED80 to 146, 223, and 312% and 139, 207, and 285%, respectively. Ajmaline increased ED50 and ED80 to 133, 175, and 251% and 135, 208, and 285%, respectively. Diltiazem increased ED50 and ED80 by 175, 236, and 334% and 158, 212, and 286%, respectively. The results of this study demonstrate a dose-dependent increase in defibrillation energy requirements by using lidocaine, diltiazem, and ajmaline. In patients with ICDs, administration of these drugs might cause a critical increase in defibrillation energy requirements, resulting in device failure.

Comparison of three cardioverter defibrillator implantation techniques: initial results with transvenous pectoral implantation.

A total of 121 patients underwent epicardial (n = 32), transvenous abdominal (n = 30), and transvenous pectoral (n = 59) ICD implants. Perioperative complications were defined as those occurring within 30 days after surgery. Hospital costs were calculated with $750 per day as a fixed charge. Duration of surgery was the time between the first skin incision and the last skin suture. Severe perioperative complications that were life-threatening or required surgical intervention occurred in the epicardial (6%) and transvenous (10%) abdominal groups, but not in the pectoral group. Perioperative mortality occurred only in the epicardial abdominal group, predominantly in patients with concomitant surgery (18%), and in 5% of patients without concomitant surgery. The duration of surgery was significantly shorter for transvenous pectoral implantation (58 +/- 15 min, P < 0.05) compared to transvenous abdominal implantation (115 +/- 38 min). Epicardial abdominal ICD implantation had the longest procedure time (154 +/- 31 min). The postimplant hospital length of stay was significantly shorter for pectoral implantation (5 +/- 3 days, P < 0.05) compared to transvenous (13 +/- 5) and epicardial (19 +/- 5) abdominal implantation. Total hospitalization costs significantly decreased in the pectoral implantation group ($4,068 +/- $2,099 for the pectoral group vs $14,887 +/- $4,415 and $9,975 +/- $3,657 for the epicardial and the transvenous abdominal group, respectively, P < 0.05). These initial results demonstrate the advantage of transvenous pectoral ICD implantation in terms of perioperative complications, procedure time, hospital length of stay, and hospitalization costs.

Implantation of a unipolar cardioverter/defibrillator system under local anaesthesia.

OBJECTIVE: To evaluate prospectively the safety and feasibility of the implantation of cardioverter/defibrillator systems under local anaesthesia. Conventionally, cardioverter/defibrillator systems are implanted under general anaesthesia. With the development of single-lead transvenous unipolar cardioverter/defibrillator systems for subpectoral implantation a pacemaker-like approach for device implantation appears applicable. METHODS: Implantation of a single-lead transvenous unipolar cardioverter/defibrillator under local anaesthesia with sedation for defibrillation threshold testing was performed in 37 consecutive patients. The presenting arrhythmia was ventricular fibrillation in 13 patients, and monomorphic ventricular tachycardia in 24 patients. A 1% lidocaine solution was used for local anaesthesia, and midazolam was applied for sedation to perform defibrillation threshold testing. Arterial blood pressure, arterial oxygen saturation and heart rate were monitored throughout the procedure. The patient's tolerance of the implantation procedure was evaluated with a standardized questionnaire. RESULTS: The unipolar transvenous cardioverter/defibrillator system was implanted successfully in all patients under local anaesthesia. During defibrillation threshold testing, sufficient sedation was achieved with 12.5 +/- 3.7 mg midazolam. For determination of the defibrillation threshold 5.9 +/- 1.4 episodes of ventricular fibrillation were induced. The mean defibrillation threshold was 13.1 +/- 5.5 J, and the mean duration of the implantation procedure was 68 +/- 30 min. Mean heart rate, mean arterial blood pressure and arterial oxygen saturation were not significantly different before and after defibrillation threshold testing. Twenty-six patients (70%) were symptom-free throughout the implantation procedure; most of the remaining patients reported minor symptoms. There were no complications, and patients were discharged 2.2 +/- 0.7 days after implantation. In 12 patients, post-implant testing of the implantable cardioverter/defibrillators was performed successfully, without sedation, 2.8 +/- 1.4 days after as an outpatient procedure. CONCLUSION: Single-lead unipolar transvenous implantable cardioverter/defibrillator systems can be safely implanted under local anaesthesia with mild sedation for defibrillation threshold testing. The procedure is well tolerated.

Cardiac involvement in systemic sclerosis.

OBJECTIVE: To assess the incidence and extent of cardiac involvement in systemic sclerosis (SSc) patients with no apparent cardiac symptoms. METHODS: Surface electrocardiography, ambulatory electrocardiography, radionuclide ventriculography, myocardial scintigraphy, and echocardiography were performed in 18 patients. RESULTS: These studies demonstrated ventricular tachycardia in 1 patient, nonsustained ventricular tachycardia in 5, supraventricular tachycardia in 6, decreased left ventricular ejection fraction in 2, decreased right ventricular ejection fraction in 8, and stress-induced reversible myocardial perfusion abnormalities in 6. CONCLUSION: These observations demonstrate a high rate of cardiac abnormalities in SSc patients without cardiac symptoms.

Serum osteocalcin levels in primary hyperparathyroidism.

The serum levels of osteocalcin, a 49-amino-acid bone-matrix protein, have been found to be a specific biochemical parameter of bone formation. The aim of our study was to compare the sensitivity of serum osteocalcin levels with that of alkaline phosphatase in the evaluation of patients with primary hyperparathyroidism. In 40 patients with biochemically and histologically confirmed primary hyperparathyroidism, the serum levels of osteocalcin, intact parathyroid hormone, alkaline phosphatase, calcium, phosphorus, and creatinine were determined preoperatively. The serum levels of osteocalcin were elevated in 22 patients (55%), whereas the serum levels of alkaline phosphatase were increased in 18 patients (45%). In 10 patients (25%) the serum levels of osteocalcin, but not those of alkaline phosphatase, were increased, whereas in six patients the activity of alkaline phosphatase was high, but the serum osteocalcin levels were normal. When the biochemical data of the patients with increased serum osteocalcin levels were compared with those of the patients with serum osteocalcin levels within the normal range, the serum levels of intact parathyroid hormone and alkaline phosphatase were significantly increased in the group of patients with elevated serum osteocalcin levels. Our data indicate that serum osteocalcin levels might be a clinically useful additional parameter in the evaluation of patients with primary hyperparathyroidism.

Evaluating antiarrhythmic strategies: a knowledge-based system for exploring clinical data.

Medical therapy for cardiac arrhythmias is still to a large extent based on empirical methods. Assessing and evaluating different therapeutical strategies constitutes the starting point for inducing decision methods to select the appropriate regimen for an individual patient. We designed a computer-based system that establishes a set of heuristic rules linking attributes in a data base of patients with rhythm disturbances. A feasibility analysis conducted on a small set of 23 patients indicated that constraints on the number of attributes and their clinical relevancy together with a representation scheme for temporal changes have to be incorporated to provide for a useful and efficient algorithm.