Unsupervised detection and classification of heartbeats using the dissimilarity matrix in PCG signals.

BACKGROUND AND OBJECTIVE: Auscultation is the first technique applied to the early diagnose of any cardiovascular disease (CVD) in rural areas and poor-resources countries because of its low cost and non-invasiveness. However, it highly depends on the physician's expertise to recognize specific heart sounds heard through the stethoscope. The analysis of phonocardiogram (PCG) signals attempts to segment each cardiac cycle into the four cardiac states (S1, systole, S2 and diastole) in order to develop automatic systems applied to an efficient and reliable detection and classification of heartbeats. In this work, we propose an unsupervised approach, based on time-frequency characteristics shown by cardiac sounds, to detect and classify heartbeats S1 and S2. METHODS: The proposed system consists of a two-stage cascade. The first stage performs a rough heartbeat detection while the second stage refines the previous one, improving the temporal localization and also classifying the heartbeats into types S1 and S2. The first contribution is a novel approach that combines the dissimilarity matrix with the frame-level spectral divergence to locate heartbeats using the repetitiveness shown by the heart sounds and the temporal relationships between the intervals defined by the events S1/S2 and non-S1/S2 (systole and diastole). The second contribution is a verification-correction-classification process based on a sliding window that allows the preservation of the temporal structure of the cardiac cycle in order to be applied in the heart sound classification. The proposed method has been assessed using the open access databases PASCAL, CirCor DigiScope Phonocardiogram and an additional sound mixing procedure considering both Additive White Gaussian Noise (AWGN) and different kinds of clinical ambient noises from a commercial database. RESULTS: The proposed method outperforms the detection and classification performance of other recent state-of-the-art methods. Although our proposal achieves the best average accuracy for PCG signals without cardiac abnormalities, 99.4% in heartbeat detection and 97.2% in heartbeat classification, its worst average accuracy is always above 92% for PCG signals with cardiac abnormalities, signifying an improvement in heartbeat detection/classification above 10% compared to the other state-of-the-art methods evaluated. CONCLUSIONS: The proposed method provides the best detection/classification performance in realistic scenarios where the presence of cardiac anomalies as well as different types of clinical environmental noises are active in the PCG signal. Of note, the promising modelling of the temporal structures of the heart provided by the dissimilarity matrix together with the frame-level spectral divergence, as well as the removal of a significant number of spurious heart events and recovery of missing heart events, both corrected by the proposed verification-correction-classification algorithm, suggest that our proposal is a successful tool to be applied in heart segmentation.

Inhibition of R-[3H]-baclofen binding to rat brain synaptic membranes by a homologous series of phenyl alcohol amides anticonvulsants and their evaluation as GABAB receptor blockers.

The inhibition of the specific R-[3H]-baclofen binding to GABAB (gamma-aminobutyric acid) sites by a homologous series of phenyl alcohol amides was tested in rat brain synaptic membranes. Some of these phenyl alcohol amides were designed as anticonvulsants as well as antagonists of the GABAB receptor. These anticonvulsants showed a high affinity to the GABAB receptor. DL-2-hydroxy-2-(4'-chlorophenyl)butyramide and DL-3-hydroxy-3-(4'-chlorophenyl)pentanamide (DL-Cl-HEPP) were as effective as GABA and R-baclofen and were the most potent examined. DL-2-hydroxy-2-phenylbutyramide (DL-HEPA), (+)-HEPA, (-)-HEPA, DL-3-hydroxy-3-phenylpentanamide (DL-HEPP) and DL-4-hydroxy-4-phenylhexanamide (DL-HEPB) were as potent as DL-baclofen. The phenyl alcohol amides with fluorine in the para position of the phenyl ring were less active than DL-2-hydroxysaclofen. DL-4-hydroxy-4-(4'-chlorophenyl)hexanamide was the least active of the series. In addition, R-baclofen antagonized very effectively the anticonvulsant activity of both DL-HEPP and DL-Cl-HEPP in a dose-dependent fashion. These results support the assumption that some of these phenyl alcohol amides anticonvulsants are GABAB receptor blockers.

In vivo and in vitro effects of phenytoin (PHT) on ATPases and [14C]-PHT binding in synaptosomes and mitochondria from rat cerebral cortex.

The effect of phenytoin (PHT) on Na(+)-K(+)-ATPase and Mg(2+)-ATPase activities and on [14C]-PHT binding in vitro to synaptosomal and mitochondrial subcellular fractions from rat cerebral cortex was studied after chronic PHT treatment. Synaptosomal and mitochondrial fractions were characterized with plasma membrane and mitochondrial enzymatic markers. Synaptosomal Na(+)-K(+)-ATPase was not affected in vitro by PHT 1-200 microM or by chronic treatment with 2-50 mg/kg/day of the unlabeled drug for 8 days. Mitochondrial Mg(2+)-ATPase was significantly stimulated by PHT after chronic treatment with 5 mg/kg/day for 8 days; reaching maximal effect (76%), at 10-25 mg/kg. PHT had no effect on mitochondrial Mg(2+)-ATPase when added in vitro. [14C]-PHT binding in vitro to the subcellular fractions was determined by dialysis to assess in vivo binding of the unlabeled PHT during chronic treatment. Indeed, [14C]-PHT bound to synaptosomes was significantly reduced by chronic PHT treatment from 218 +/- 10 to 119 +/- 11 pmol/mg protein after 1 week of treatment; a similar effect was obtained after 2-3 weeks with 10 mg/kg/day. Mitochondrial fraction bound 117 +/- 10 pmol/mg protein labeled PHT. Chronic treatment with unlabeled PHT also reduced the amount of [14C]-PHT bound to 19.9 +/- 2.2 pmol/mg protein. These results show slow reversible PHT in vivo binding to synaptosomes and mitochondrias from rat cerebral cortex, supporting the idea that the modulatory action of PHT on Na+ and Ca2+ permeabilities are mediated through these slow reversible binding proteins. The data also suggest a possible role of intrasynaptosomal mitochondria in [Ca2+]i buffering.

A new homologous series of anticonvulsants: phenyl alcohol amides. Synthesis and pharmacological evaluation.

The anticonvulsant activity of a homologous series of phenyl alcohol amides is described. (+-)-2-Hydroxy-2-phenylbutyramide (1), (+-)-3-hydroxy-3-phenylpentanamide (2) and (+-)-4-hydroxy-4-phenylhexanamide (3) were prepared and tested for their anticonvulsant profile and neurotoxicity. 1, 2 and 3 exhibited a broad profile of anticonvulsant activity and a similar significant activity in the seizures provoked by maximal electroshock, pentetrazol, 4-aminopyridine, bicuculline and thiosemicarbazide, but in the strychnine and picrotoxin tests, the protection was variable. The rotarod ataxia test was used to evaluate their neurotoxicity. In this test 2 possesses the lowest neurotoxicity.