Use of monoclonal antibodies against myosin light chains 1 to detect the corresponding antigen in blood of patients with myocardial infarction

Research Institute of Human Genetics, All-Union Medical Genetics Research Center, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. D. Ado.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 112, No. 10, pp. 416–417, October, 1991.     

Vergleichende Untersuchungen der Bilirubinämie und Kreislaufzeit bei Dekompensation des Herzens

Zusammenfassung Es wurden₃₀₀ Bestimmungen der Kreislaufzeit mit Lobelin, Decholin und Tachimetrine bei₄₉ Kranken ausgeführt. Von diesen Kranken waren 30 herzkrank ohne primäre Leberschädigung, davon 23 dekompensiert und 7 nichtdekompensiert. Bei denselben Kranken wurde gleichzeitig auch die Bilirubinämie bestimmt.Es wurde gefunden, daß die Kreislaufzeit am meisten beiden dekompensierten Herzkranken vergrößert war, bei ihnen war auch der Durchschnittswert der Bilirubinämie am größten. Die Gallenfarbstoffwerte im Blute bei dekompensierten Herzfällen unterliegen kleineren Veränderungen als die Kreislaufzeit, die von vielen Faktoren abhängt. Obwohl die Kreislaufzeiten größere vorübergehende Schwankungen aufweisen, laufen sie im großen und ganzen mit den Werten der Bilirubinämie parallel, und zwar besonders in den Fällen einer klinischen Besserung der Dekompensation. Das gilt vor allem für die mit der Lobelinmethode erhaltenen Kreislaufzeiten wohl deshalb, weil das eine objektive Methode ist.Vermindert sich die Bilirubinmenge im Blute und verkleinert sich gleichzeitig die vorher erhöhte Kreislaufzeit, so kann man das für eine sichere Verbesserung des Zustandes des Herzkranken halten. Im Gegensatze dazu sind die gleichzeitige Vermehrung der Bilirubinämie und die Vergrößerung der Kreislaufzeit Zeichen der Verschlechterung der Herzerkrankung.Während Decholin und Tachimetrine bei anderen Kranken eine gewisse Bedeutung für die Bestimmung der Kreislaufzeit haben, sind sie bei dekompensierten Herzkranken nicht geeignet.     

The importance of evaluating findings given activity level propositions in order to avoid misleading evidence

ABSTRACT

The advancement of DNA technology comes with the increased sensitivity of amplification systems, where DNA traces are routinely detected without a known biological source. These systems also have increased discriminating capacity, providing larger likelihood ratios (LRs) when a corresponding DNA profile is observed. Questions in court are shifting from identity to transfer mechanism, where the presence of an individual’s DNA is conceded by both parties, but the activities that led to its deposition is in dispute. One way of handling propositions developed at the activity level is with the use of graphical structures known as Bayesian Networks (BNs). The following is an evaluation of a case, given activity level propositions, through the application of BNs. Alternative case findings will be explored for the given scenario to show the potential value of the DNA evidence for different outcomes within the broader case context.     

Impaired Vestibular Function and Low Bone Mineral Density: Data from the Baltimore Longitudinal Study of Aging

Animal studies have demonstrated that experimentally induced vestibular ablation leads to a decrease in bone mineral density, through mechanisms mediated by the sympathetic nervous system. Loss of bone mineral density is a common and potentially morbid condition that occurs with aging, and we sought to investigate whether vestibular loss is associated with low bone mineral density in older adults. We evaluated this question in a cross-sectional analysis of data from the Baltimore Longitudinal Study of Aging (BLSA), a large, prospective cohort study managed by the National Institute on Aging (N = 389). Vestibular function was assessed with cervical vestibular evoked myogenic potentials (cVEMPs), a measure of saccular function. Bone mineral density was assessed using dual-energy X-ray absorptiometry (DEXA). In two-way t test analysis, we observed that individuals with reduced vestibular physiologic function had significantly lower bone mineral density. In adjusted multivariate linear regression analyses, we observed that older individuals with reduced vestibular physiologic function had significantly lower bone mineral density, specifically in weight-bearing hip and lower extremity bones. These results suggest that the vestibular system may contribute to bone homeostasis in older adults, notably of the weight-bearing hip bones at greatest risk of osteoporotic fracture. Further longitudinal analysis of vestibular function and bone mineral density in humans is needed to characterize this relationship and investigate the potential confounding effect of physical activity.     

Development of a non-denaturing electrophoresis system for characterization of neutralizing epitopes on HPV virus-like particles

The precise structure of the HPV16 major neutralizing epitope recognized by H16.V5 monoclonal antibody is unknown. This paper describes a novel polyacrylamide gel electrophoresis (PAGE) for separation of HPV virus-like particles (VLPs) using cetyltrimethylammonium chloride (CTAC) as a solubilizing agent. CTAC PAGE employs KOH/CH3CO2H (pH 4-5.4) as a buffer system, K+ as the leading ion and 3-aminopropionic acid as a trailing ion. The unique characteristics of a cationic electrophoresis system allow separation of VLPs without heat denaturation. HPV VLP gel migration patterns were dependent on pre-treatment conditions: (1) thiol-agent reduction alone resulted in a 174 kDa band (interpreted as a L1 trimer), a 53 kDa band (size of the L1 monomer), as well as higher Mr aggregates consistent with a pentamer size; (2) both heat denaturation and thiol-agent reduction resulted in a 53 kDa band. Western blot analysis showed that the 174 kDa L1 trimer was strongly immunoreactive with H16.V5 and HPV16 VLP ELISA positive human sera, whereas no reactivity was seen with the monomeric L1 unit. These data suggest that a structure consistent with the migration pattern of a L1 trimer contains the major neutralizing epitope recognized by the H16.V5 MAb and human sera.     

Cost-Effectiveness Models for Chronic Obstructive Pulmonary Disease: Cross-Model Comparison of Hypothetical Treatment Scenarios

ObjectivesTo compare different chronic obstructive pulmonary disease (COPD) cost-effectiveness models with respect to structure and input parameters and to cross-validate the models by running the same hypothetical treatment scenarios.MethodsCOPD modeling groups simulated four hypothetical interventions with their model and compared the results with a reference scenario of no intervention. The four interventions modeled assumed 1) 20% reduction in decline in lung function, 2) 25% reduction in exacerbation frequency, 3) 10% reduction in all-cause mortality, and 4) all these effects combined. The interventions were simulated for a 5-year and lifetime horizon with standardization, if possible, for sex, age, COPD severity, smoking status, exacerbation frequencies, mortality due to other causes, utilities, costs, and discount rates. Furthermore, uncertainty around the outcomes of intervention four was compared.ResultsSeven out of nine contacted COPD modeling groups agreed to participate. The 5-year incremental cost-effectiveness ratios (ICERs) for the most comprehensive intervention, intervention four, was €17,000/quality-adjusted life-year (QALY) for two models, €25,000 to €28,000/QALY for three models, and €47,000/QALY for the remaining two models. Differences in the ICERs could mainly be explained by differences in input values for disease progression, exacerbation-related mortality, and all-cause mortality, with high input values resulting in low ICERs and vice versa. Lifetime results were mainly affected by the input values for mortality. The probability of intervention four to be cost-effective at a willingness-to-pay value of €50,000/QALY was 90% to 100% for five models and about 70% and 50% for the other two models, respectively.ConclusionsMortality was the most important factor determining the differences in cost-effectiveness outcomes between models.     

Cost-effectiveness of roflumilast as an add-on treatment to long-acting bronchodilators in the treatment of COPD associated with chronic bronchitis in the United Kingdom

Objective

To estimate the cost-effectiveness of adding a selective phosphodiesterase-4 inhibitor, roflumilast, to a long-acting bronchodilator therapy (LABA) for the treatment of patients with severe-to-very severe chronic obstructive pulmonary disease (COPD) associated with chronic bronchitis with a history of frequent exacerbations from the UK payer perspective.

Methods

A Markov model was developed to predict the lifetime cost and outcomes [exacerbations rates, life expectancy, and quality-adjusted life years (QALY)] in patients treated with roflumilast, which showed a reduction in the exacerbation rates and lung function improvement in a pooled analysis from two clinical trials, M2-124 and M2-125. Sensitivity analyses were conducted to explore the impact of uncertainties on the cost-effectiveness.

Results

The addition of roflumilast to concomitant LABA reduced the number of exacerbations from 15.6 to 12.7 [2.9 (95 % CI 0.88–4.92) exacerbations avoided] and increased QALYs from 5.45 to 5.61 [0.16 (95 % CI 0.02–0.31) QALYs gained], at an incremental cost of £3,197 (95 % CI £2,135–£4,253). Cost in LABA alone and LABA + roflumilast were £16,161 and £19,358 respectively. The incremental cost-effectiveness ratios in the base case were £19,505 (95 % CI £364–£38,646) per quality-adjusted life-year gained and 18,219 (95 % CI £12,697–£49,135) per life-year gained. Sensitivity analyses suggest that among the main determinants of cost-effectiveness are the reduction of exacerbations and the case fatality rate due to hospital-treated exacerbations. Probabilistic sensitivity analysis suggests that the probability of roflumilast being cost-effective is 82 % at willingness-to-pay £30,000 per QALY.

Conclusions

The addition of roflumilast to LABA in the treatment of patients with severe-to-very severe COPD reduces the rate of exacerbations and can be cost-effective in the UK setting.     

Understanding neurobehavioral genetics of zebrafish

Abstract

Due to its fully sequenced genome, high genetic homology to humans, external fertilization, fast development, transparency of embryos, low cost and active reproduction, the zebrafish (Danio rerio) has become a novel promising model organism in biomedicine. Zebrafish are a useful tool in genetic and neuroscience research, including linking various genetic mutations to brain mechanisms using forward and reverse genetics. These approaches have produced novel models of rare genetic CNS disorders and common brain illnesses, such as addiction, aggression, anxiety and depression. Genetically modified zebrafish also foster neuroanatomical studies, manipulating neural circuits and linking them to different behaviors. Here, we discuss recent advances in neurogenetics of zebrafish, and evaluate their unique strengths, inherent limitations and the rapidly growing potential for elucidating the conserved roles of genes in neuropsychiatric disorders.