Non invasive hemodynamic monitorization for AV interval optimization in patients with ventricular resynchronization therapy.

INTRODUCTION AND OBJECTIVE: In patients (pts) with dilated cardiomyopathy and intraventricular conduction disturbances, resynchronization therapy improves cardiac function and functional capacity. Determination of the optimal AV interval is essential to optimize the therapy results and various methods have been used in daily practice to obtain such an interval. The aim of this work is to assess optimal AV determined by impedance cardiography and compare it to the interval previously obtained by transmitral flow Doppler echocardiography. PATIENTS: Seven pts were evaluated, five men, mean age of 61 +/- 10 years, with dilated cardiomyopathy, intra-ventricular conduction disturbances and heart failure, New York Heart Association functional class III or IV. Four pts had ischemic cardiomyopathy and three idiopathic. All pts had an implanted cardioverter-defibrillator with cardiac resynchronization. METHODS: The optimal AV delay was estimated by transmitral flow pulsed Doppler using the method previously described by Ritter. Subsequently, cardiac output (CO) was determined by impedance cardiography. CO was estimated for different AV delays, beginning with 80 ms until occurrence of fusion QRS. The optimal AV delay was defined as the value corresponding to the highest measured CO. The ideal AV interval was compared between the two methods used. RESULTS: The AV delay determined by echocardiography varied between 120 and 170 ms (134 +/- 17 ms). The optimum AV delay based on CO estimation varied between 110 and 190 ms (137 +/- 26 ms). There was a correlation between the delays determined by the two methods (r = 0.844; p = 0.017). CONCLUSIONS: In pts undergoing ventricular resynchronization therapy, AV delay optimization based on CO determined by impedance cardiography is comparable to that measured by transmitral flow pulsed Doppler. However, impedance cardiography seems a more objective and simpler technique.     

Intracerebral grafting impedes hippocampal cell loss during withdrawal after long-term alcohol consumption in rats

We previously found that, in the hippocampal formation as well as other central nervous system regions, withdrawal from alcohol following long periods of ingestion did not impede the ethanol-induced degenerative changes, including cell loss: on the contrary, neuronal degeneration was found to be increased in withdrawn rats. By grafting withdrawn rats either with immature hippocampal blocks or with suspensions of cultured astrocytes, we hoped to arrest the process of cell loss or even reverse it, because it is known that grafted material might display trophic and eventually protective effects in conditions of brain damage. The dentate granule and hippocampal CA3 pyramidal cells were counted both in the grafted hemisphere and in the contralateral one. Grafts of astrocyte suspensions did not interfere with the ongoing process of cell death in withdrawn rats. Conversely, grafts of hippocampal tissue impeded the degeneration observed in the granule and pyramidal cells of the grafted hemisphere, although in the contralateral one the cell loss persisted. We therefore conclude that the protective effect displayed by solid grafts might be a local process dependent on the release of diffusible trophic agents. We cannot explain the absence of any effect displayed by astroglial grafts, inasmuch as in different experimental situations such an effect was described.     

Critical analysis of the application of Bayes' theorem to sequential testing in the noninvasive diagnosis of coronary artery disease

The utility of Bayes' theorem in the noninvasive diagnosis of coronary artery disease (CAD) was analyzed in 147 patients who underwent electrocardiographic stress testing, thallium-201 perfusion imaging and coronary angiography. Eighty-nine patients had typical anginal chest discomfort and 58 had atypical chest pain. Sensitivity and specificity of the tests and prevalence of CAD at each level of testing were tabulated and compared with the results generated from Bayes' theorem. The sensitivity of electrocardiographic stress was higher in patients with multivessel CAD than in patients with 1-vessel CAD. Sensitivity, but not specificity, of each test was dependent, in part, on the result of the other test. However, the probabilities calculated from Bayes' theorem when used for sequential testing are remarkably close to the tabulated data. Thus, Bayes' theorem is useful clinically despite some evidence of test dependence. Sequential test analysis by Bayes' theorem is most useful in establishing or ruling out a diagnosis when the pretest prevalence is approximately 50% and when the 2 tests are concordant.     

Mercuric chloride toxicity in rat liver mitochondria and isolated hepatocytes

The effects of mercuric chloride on isolated rat liver mitochondria and freshly isolated rat hepatocytes were investigated. Mercuric chloride (in the μM range) depresses state 3 respiration, suggesting a strong effect at the level of the phosphorylation system. It also stimulates state 4 respiration and decreases mitochondrial membrane potential, suggesting an uncoupling action. In isolated hepatocytes, mercuric chloride causes a dose- and time-dependent cell death, accompanied by depletion of intracellular glutathione. Furthermore, mercuric chloride decreases intracellular ATP and ADP levels simultaneously with increasing AMP concentration, indicating fast hydrolysis of ATP without adequate rephosphorylation. From this study we can conclude that the bioenergetic lesion promoted by mercuric chloride seems to be sufficient to explain lethal hepatocyte injury.     

Evidence of reorganization in the hippocampal mossy fiber synapses of adult rats rehabilitated after prolonged undernutrition

We have previously demonstrated that prolonged low-protein diet leads to irreversible cell loss in the hippocampal formation of the adult rat. Because the extent of the resulting hippocampal synaptic alterations is not well characterized, we studied the contacts between mossy fibers and the dendritic excrescences of CA3 pyramidal cells (MF-CA3 synapses) using quantitative methods. Moreover, we investigated whether rehabilitation from undernutrition would influence the morphology of hippocampal synapses. To address these issues, three groups of adult rats were compared: (a) rats fed with a normal diet for 12 months (control rats); (b) rats treated during the same period with low-protein diet (undernourished rats); and (c) rats undernourished for 6 months and then switched to normal diet for 6 months (recovery rats). Timm staining and electron microscopy were employed to estimate the volume of the mossy fiber system and the number and related quantitative features of MF-CA3 synapses. The volume of the suprapyramidal bundle of the mossy fiber system and its total number of synapses were smaller in undernourished rats than in control and recovery animals. These parameters did not differ between the latter two groups. The size of mossy fiber terminals and dendritic excrescences and the surface area of synapses were smaller in undernourished than in control and recovery groups. Conversely, in recovery animals, the volume of the suprapyramidal bundle of the mossy fiber system, the size of mossy fiber terminals and dendritic excrescences, and the total number and surface area of synapses were similar to those of controls. These findings indicate that, following rehabilitation, the pre- and postsynaptic compartments of MF-CA3 synapses undergo structural alterations which compensate for the neuronal loss induced by undernutrition.     

Molecular model for studying the uncultivated fungal pathogen Lacazia loboi

Lacazia loboi is an uncultivated fungal pathogen of humans and dolphins that causes cutaneous and subcutaneous infections only in the tropical areas of the Americas. It was recently found by phylogenetic analysis that this unusual pathogen is closely related to Paracoccidioides brasiliensis and to the other fungal dimorphic members of the order Onygenales. That original phylogenetic study used universal primers to amplify well-known genes. However, this approach cannot be applied to the study of other proteins. We have developed a strategy for studying the gene encoding the gp43 homologous protein of P. brasiliensis in L. loboi. The gp43 protein was selected because it has been found that this P. brasiliensis antigen strongly reacts when it is used to test sera from patients with lacaziosis. The principle behind this idea was to obtain the gp43 amino acid sequence of P. brasiliensis and other homologous fungal sequences from GenBank and design primers from their aligned conserved regions. These sets of primers were used to amplify the selected regions with genomic DNA extracted from the yeast-like cells of L. loboi from experimentally infected mice. Using this approach, we amplified 483 bp of the L. loboi gp43-like gene. These sequences had 85% identity at the nucleotide level and 75% identity with the deduced amino acid sequences of the P. brasiliensis gp43 protein. The identity of the 483-bp DNA fragment was confirmed by phylogenetic analysis. This analysis revealed that the L. loboi gp43-like deduced amino acid sequence formed a strongly supported (100%) sister group with several P. brasiliensis gp43 sequences and that this taxon in turn was linked to the other fungal sequences used in this analysis. This study shows that the use of a molecular model for investigation of the genes encoding important proteins in L. loboi is feasible.     

The biological activity of auranofin: implications for novel treatment of diseases

More than 30?years ago, auranofin was developed for the treatment of rheumatoid arthritis as a substitution for the injectable gold compounds aurothiomalate and aurothioglucose. Both the ease of oral administration over intramuscular injections and more potent anti-inflammatory effects in vitro made auranofin seem like an excellent substitute for the traditional injectable gold compounds. Despite efficacy in the treatment of both rheumatoid arthritis and psoriasis, currently, auranofin is seldom used as a treatment for patients with rheumatoid arthritis as more novel anti-rheumatic medications have become available. Despite the decline in its clinical applications, research on auranofin has continued as it shows promise in the treatment of several different diseases. In recent years, advances in technology have allowed researchers to use molecular techniques to identify novel mechanisms of action of auranofin. Additionally, researchers are discovering potential new applications of auranofin. Dual inhibition of inflammatory pathways and thiol redox enzymes by auranofin makes it a new candidate for cancer therapy and treating microbial infections. This review will summarize recently obtained data on the mechanisms of action of auranofin, and potential new applications of auranofin in the treatment of various diseases, including several types of leukaemia, carcinomas, and parasitic, bacterial, and viral infections.     

Design and Implementation of a Group Prenatal Care Model for Somali Women at a Low-Resource Health Clinic

ObjectiveTo design and implement group prenatal care (GPC) for Somali women and to evaluate participants’ satisfaction, knowledge, and care engagement.DesignQuality improvement project.Setting/Local ProblemA federally qualified health center in an urban Midwestern setting, which serves a largely East African immigrant and refugee population.ParticipantsPregnant Somali women at more than 20 weeks gestation receiving prenatal care at the project site. Many participants were non–English speaking.Intervention/MeasurementsWhile honoring the 13 essential elements of CenteringPregnancy, the model was adapted to the East African population at the project site and offered to all eligible women receiving individual prenatal care at the clinic. Women attended biweekly sessions, including individual assessment and education, exposure to integrative health therapies, and group discussion. Pre- and postintervention data were collected in surveys and in-depth interviews from March through August 2017.ResultsSeventeen Somali women attended a median of two sessions (range = 1–7). Self-reported results for knowledge of safe exercise in pregnancy (p = .02), exclusive breastfeeding (p = .04), what happens in the hospital (p = .02), and stress management (p = .03) increased after GPC participation. Ninety-three percent of women preferred GPC to individual care.ConclusionWhen adapted to meet the needs of Somali women, GPC has the potential to improve care satisfaction, increase knowledge, and reduce stress during pregnancy and the postpartum period. This model may interest women and care providers in similar community health care settings.     

Long-term assessment of the Ross procedure in adults: Clinical and echocardiographic follow-up at 20 years

IntroductionThe Ross procedure is an alternative to standard aortic valve (AV) replacement in young and middle-aged patients. However, durability and incidence of reoperation remain a concern for most cardiac surgeons. Our aim was to assess very long-term clinical and echocardiographic outcomes of the Ross procedure.MethodsWe conducted a single-center retrospective analysis of 56 consecutive adult patients who underwent the Ross procedure. Mean age at surgery was 44±12 years (range, 16-65 years) and 55% were male. Clinical endpoints included overall mortality and the need for valve reoperation due to graft failure. The echocardiographic endpoint was the presence of any graft deterioration. Median clinical follow-up was 20 years (1120 patient/years).ResultsIndications for surgery were dominant aortic stenosis in 50% and isolated aortic regurgitation in 21%. Concomitant mitral valve repair was performed in 21% and a subcoronary technique was most commonly used (86%). Overall long-term survival was 91%, 80% and 77% at 15, 20 and 24 years, respectively. The survival rate was similar to the age- and gender-matched general population (p=0.44). During the follow-up period, freedom from graft reoperation was 80%. Eleven patients (31%) developed moderate AV regurgitation, three (8.6%) developed moderate pulmonary regurgitation and one (2.9%) presented moderate pulmonary stenosis.ConclusionThe Ross procedure, mostly using a subcoronary approach, proved to have good clinical and hemodynamic results, with low reoperation rates in long-term follow-up. Moderate autograft regurgitation was a frequent finding but had no significant clinical impact.