Telemonitoring predicts in advance heart failure admissions.

BACKGROUND: Heart failure (HF) is increasingly common and characterised by frequent admissions to hospital. To reduce the risk of HF hospitalisation (HFH), approaches as telemonitoring (TM) have been introduced. This study aimed to develop an algorithm for detecting patients at high risk of HFH, using daily collected physiological data (blood pressure, heart rate, weight) by non-invasive TM. METHODS: The analysis was based on home-TM data collected from a single centre as part of HF care. The prediction of HFH was considered as a signal processing and classification problem. Signal processing aimed to transform the signals to enhance the information relevant to HFH. We attempted to construct an algorithm that could identify such patterns and classify them as abnormal by assessing the predictive value of each of the monitored signals and their combinations using analysis of vectors (e.g. vectors of raw signal values, vectors of signals obtained by Multi-Resolution Analysis). RESULTS: The best predictive results were achieved with the combined used of weight and diastolic BP. The highest predictive performance was achieved using 8-day TM data (area under the receiver operator characteristic curve (AUC) 0.82±0.02). Prediction based on 4-day TM data was slightly less accurate with an AUC of 0.77±0.01. CONCLUSION: We have found that using an algorithm based on weight and diastolic blood pressure measured over 8days predicts heart failure admissions with a high degree of accuracy. The value of such an algorithm should be tested in clinical trials.

Ratsnake: a versatile image annotation tool with application to computer-aided diagnosis.

Image segmentation and annotation are key components of image-based medical computer-aided diagnosis (CAD) systems. In this paper we present Ratsnake, a publicly available generic image annotation tool providing annotation efficiency, semantic awareness, versatility, and extensibility, features that can be exploited to transform it into an effective CAD system. In order to demonstrate this unique capability, we present its novel application for the evaluation and quantification of salient objects and structures of interest in kidney biopsy images. Accurate annotation identifying and quantifying such structures in microscopy images can provide an estimation of pathogenesis in obstructive nephropathy, which is a rather common disease with severe implication in children and infants. However a tool for detecting and quantifying the disease is not yet available. A machine learning-based approach, which utilizes prior domain knowledge and textural image features, is considered for the generation of an image force field customizing the presented tool for automatic evaluation of kidney biopsy images. The experimental evaluation of the proposed application of Ratsnake demonstrates its efficiency and effectiveness and promises its wide applicability across a variety of medical imaging domains.

Image analysis framework for infection monitoring.

We present a novel framework for automatic extraction of the progress of an infection from time-series medical images, with application to pneumonia monitoring. In each image of a series, the lungs, which are the body components of interest in our study, are detected and delineated by a modified active shape model-based algorithm that is constrained by binary approximation masks. This algorithm offers resistance in the presence of infection manifestations that may distort the typical appearance of the body components of interest. The relative extent of the infection manifestations is assessed by supervised classification of samples acquired from the respective image regions. The samples are represented by multiple dissimilarity features fused according to a novel entropy-based weighted voting scheme offering nonparametric operation and robustness to outliers. The output of the proposed framework is a time series of structured data quantifying the relative extent of infection manifestations at the body components of interest over time. The results obtained indicate an improved performance over relevant state-of-the-art methods. The overall accuracy quantified by the area under receiver operating characteristic reaches 90.0 ± 2.1%. The effectiveness of the proposed framework to pneumonia monitoring, the generality, and the adaptivity of its methods open perspectives for application to other medical imaging domains.

Reduction of capsule endoscopy reading times by unsupervised image mining.

The screening of the small intestine has become painless and easy with wireless capsule endoscopy (WCE) that is a revolutionary, relatively non-invasive imaging technique performed by a wireless swallowable endoscopic capsule transmitting thousands of video frames per examination. The average time required for the visual inspection of a full 8-h WCE video ranges from 45 to 120min, depending on the experience of the examiner. In this paper, we propose a novel approach to WCE reading time reduction by unsupervised mining of video frames. The proposed methodology is based on a data reduction algorithm which is applied according to a novel scheme for the extraction of representative video frames from a full length WCE video. It can be used either as a video summarization or as a video bookmarking tool, providing the comparative advantage of being general, unbounded by the finiteness of a training set. The number of frames extracted is controlled by a parameter that can be tuned automatically. Comprehensive experiments on real WCE videos indicate that a significant reduction in the reading times is feasible. In the case of the WCE videos used this reduction reached 85% without any loss of abnormalities.

Epidemiologic trends in lung cancer over two decades in Northern Greece: an analysis of bronchoscopic data.

BACKGROUND AND AIM: The relative frequency of histological subtypes of lung cancer in Europe has changed dramatically during the 20th century. The aim of this study was to explore the changing epidemiology of lung cancer in Northern Greece over the last two decades. METHODS: From the extensive database of the Bronchoscopy Unit of the G. Papanicolaou General Hospital, Thessaloniki, Greece, we identified all patients with a histologic and/or cytologic report positive for lung cancer over two consecutive decades. RESULTS: Between 1/1/1986 and 31/12/2005 we identified 9981 patients with specimens positive for lung cancer. A significant increase in mean patient age was observed during the second decade (64.8 +/- 9.4 vs. 62.1 +/- 8.9, p=0.001). Men developed lung cancer ten times more often than women. The predominant histological type was squamous cell cancer in males (4203 cases, 45.7%) and adenocarcinoma (418 cases, 52.6%) in females. The number of lung cancer cases was significantly higher during the second decade compared to the first decade (5766 cases [57.8%] vs. 4215 cases [42.2%], respectively, p<0.001). There was a significant decrease in the percentage of squamous cell carcinoma in males in the second decade (2317 cases [44.1%] vs. 1886 cases [48.0%], p<0.001), and an increase in adenocarcinoma (1021 cases [19.4%] vs. 609 [11.6%], p<0.001). In females, the relative incidence of adenocarcinoma was decreased and that of squamous cell carcinoma was increased, but not significantly. There was no obvious change in the incidence of small cell lung cancer. Neoplastic lesions were most often located in the upper lobes. CONCLUSION: The number of lung cancer cases has increased in the last decade. Squamous lung cancer appears to be decreasing in men and increasing in women. Adenocarcinoma appears to be increasing in men and decreasing in women. There appears to be no change in small cell lung cancer. During the second decade there has been a significant decrease in the male: female ratio.

Microarray-MD: a system for exploratory analysis of microarray gene expression data.

In this paper, we present Microarray Medical Data explorer (Microarray-MD), a novel software system that is able to assist in the exploratory analysis of gene expression microarray data. It implements a combination scheme of multiple Support Vector Machines, which integrates a variety of gene selection criteria and allows for the discrimination of multiple diseases or subtypes of a disease. The system can be trained and automatically tune its parameters with the provision of pathologically characterized gene expression data to its input. Given a set of new, uncharacterized, patient's data as input, it outputs a decision on the type or the subtype of a disease. A graphical user interface provides easy access to the system operations and direct adjustment of its parameters. It has been tested on various publicly available datasets. The overall accuracy it achieves was estimated to exceed 90%.

CoLD: a versatile detection system for colorectal lesions in endoscopy video-frames.

In this paper, we present CoLD (colorectal lesions detector) an innovative detection system to support colorectal cancer diagnosis and detection of pre-cancerous polyps, by processing endoscopy images or video frame sequences acquired during colonoscopy. It utilizes second-order statistical features that are calculated on the wavelet transformation of each image to discriminate amongst regions of normal or abnormal tissue. An artificial neural network performs the classification of the features. CoLD integrates the feature extraction and classification algorithms under a graphical user interface, which allows both novice and expert users to utilize effectively all system's functions. It has been developed in close cooperation with gastroenterology specialists and has been tested on various colonoscopy videos. The detection accuracy of the proposed system has been estimated to be more than 95%. As it has been resulted, it can be used as a supplementary diagnostic tool for colorectal lesions.

Role of beta-adrenergic receptor subtypes in lipolysis.

In vitro lipolysis stimulated by low (-)-isoprenaline concentrations (< or =30 nM) in epididymal white adipocytes from Sprague-Dawley rats was inhibited at least 60-80% by the specific beta1-antagonists LK 204-545 and CGP 20712A (1 microM), suggesting that at these low (10 nM) concentrations of (-)-isoprenaline lipolysis was primarily (80%) but not solely mediated via beta1-adrenergic receptors. Low concentrations (100 nM) of (-)-noradrenaline and formoterol also confirmed a role for beta1-adrenergic receptors in mediating lipolysis at low concentrations of these agonists. At higher agonist concentrations, beta3-adrenergic receptors were fully activated and were the dominant beta-adrenergic receptor subtype mediating the maximum lipolytic response, and the maximum response was not affected by the beta1-antagonists, demonstrating that the beta3-receptor is capable of inducing maximum lipolysis on its own. Studies of lipolysis induced by the relatively beta2-selective agonist formoterol in the presence of beta1-blockade (1 microM CGP 20712A) demonstrated the inability of the beta2-selective antagonist ICI 118-551 to inhibit the residual lipolysis at concentrations of ICI 118-551 < or = 1 microM. Higher concentrations of ICI 118-551 inhibited the residual formoterol-induced lipolysis competetively, but with low affinity (approximately 500-fold lower than its beta2-adrenergic receptor pA2, 7.80 +/- 0.21), suggesting that formoterol was not acting via beta2-adrenergic receptors. These data are consistent with beta1-adrenergic receptors playing an important role in lipolysis at physiological but not pharmacological concentrations of catecholamines and that beta2-adrenergic receptors play no obvious direct role in mediating beta-adrenergic receptor agonist-induced lipolysis in vitro. Finally, racemic-SR 59230A, unlike the pure (S, S)-isomer (a beta3-selective antagonist), was found to be a nonselective antagonist at the three beta-adrenergic receptor subtypes, showing that the other enantiomers have different selectivity.

LK 204-545, a highly selective beta1-adrenoceptor antagonist at human beta-adrenoceptors.

LK 204-545 ((+/-)-1-(2-(3-(2-cyano-4-(2-cyclopropyl-methoxy-ethoxy)phenoxy)-2-hydro xy-propyl-amino)-ethyl)-3-(4-hydrxy-phenyl) urea), an antagonist that possesses high beta1-/beta2-selectivity in the rat, and a range of cardio-selective and non-selective beta-adrenoceptor antagonists were examined to compare their radioligand binding affinities for human beta1-, beta2- and beta3-adrenoceptors transfected into CHO cells. LK 204-545 and CGP 20712A displayed the highest beta1-/beta2- (approximately 1800 and approximately 650, respectively) and beta1-/beta3-selectivity (approximately 17000 and approximately 2200, respectively) at human beta-adrenoceptors with LK 204-545 being approximately 2.75-fold more beta1-/beta2-selective and approximately 8-fold beta1-/beta3-selective than CGP 20712A. The high potency of LK 204-545 at transfected human beta1-adrenoceptors and in functional models of rat beta1-adrenoceptors together with its high selectivity, identify it as a useful ligand for studying beta1-adrenoceptors and suggest that it may be the preferred ligand for human beta-adrenoceptor studies.

beta(1)- and beta(2)-Adrenoceptor antagonist activity of a series of para-substituted N-isopropylphenoxypropanolamines.

To further explore the structure-activity relationships of beta-adrenoceptor (beta-AR) antagonists, a series of 25 para-substituted N-isopropylphenoxy-propanolamines were synthesised, nine of which are new compounds. All have been examined for their ability to antagonise beta(1)-ARs in rat atria and beta(2)-ARs in rat trachea. Substitution in the para-position of the phenyl ring is thought to confer beta(3)-specificity and the selectivity of these compounds for the beta(1)-AR ranges from 1.5-234. None of the compounds tested were selective for the beta(2)-AR. Of the 25 compounds studied, 22 had reasonable (pA(2) > 7) potencies for the rat beta(1)-AR. Only compound 1 displayed reasonable (pA(2) > 7) potency for the rat beta(2)-AR. Twenty two compounds were used as the training set for comparative molecular field analysis (CoMFA) of antagonist potency (pA(2)) at the rat beta(1)- and beta(2)-ARs. The inclusion of a number of additional physical characteristics improved the QSAR analysis over models derived solely using the CoMFA electrostatic and steric fields. The final models predicted the beta(1)- and beta(2)-AR potency of the compounds in the training set with high accuracy (r(2) = 0.93 and 0.86 respectively). The final beta(1)-AR model predicted the beta(1)-potencies of two out of the three test compounds, not included in the training set, with residual pA(2) values < -0.14, whereas the test compounds were not as well predicted by our final beta(2)-AR model (residual pA(2) values < -0.38).

[3H]Rilmenidine-labelled imidazoline-receptor binding sites co-localize with [3H]2-(benzofuranyl)-2-imidazoline-labelled imidazoline-receptor binding sites and monoamine oxidase-B in rabbit, but not rat, kidney.

The distribution and relative densities of imidazoline-receptor binding sites (I-RBS) and monoamine oxidase (MAO)-A and -B enzyme(s) in rat and rabbit kidney were compared autoradiographically using fixed nanomolar concentrations of [3H]rilmenidine and [3H]2-(benzofuranyl)-2-imidazoline ([3H]2-BFI) to label I-RBS, and [3H]RO41-1049 and [3H]RO19-6327 to label MAO-A and -B isoenzymes, respectively. In rat kidney, high densities of I-RBS labelled by [3H]rilmenidine were observed in the cortex and outer stripe (120-280 fmol/mg tissue), in contrast to low I-RBS densities labelled by [3H]2-BFI (<4 fmol/mg). A relatively high density of [3H]RO41-1049 binding to MAO-A enzyme was present in all regions of the rat kidney (160-210 fmol/mg) compared with a low density of [3H]RO19-6327 binding to MAO-B (< 25 fmol/mg). Comparison of MAO-A and -B distributions with that of [3H]rilmenidine-labelled I-RBS strongly suggests a lack of association in rat kidney. Similarly, the extremely low densities of [3H]2-BFI-labelled I2-RBS in rat kidney contrasts with the density of MAO-A, but is consistent with the low density of MAO-B. Rabbit kidney cortex and outer stripe contained high relative densities of [3H]rilmenidine-labelled I-RBS (200-215 fmol/mg) and [3H]2-BFI-labelled I2-RBS (45-60 fmol/mg) with lower densities in the inner stripe and inner medulla (< or = 100 and 30 fmol/mg respectively). A high density of MAO-A binding was observed in the inner stripe (515 fmol/mg) with lower levels in the cortex and outer stripe (100-240 fmol/mg), while high densities of MAO-B binding were observed in the cortex and outer stripe (290-450 fmol/mg) with lower levels in the inner stripe (65 fmol/mg). The correlation between the localization of [3H]rilmenidine-labelled I-RBS and [3H]RO19-6327-labelled MAO-B in rabbit kidney (r = 0.87, P = 0.057) suggest that [3H]rilmenidine may label a binding site co-existent with MAO-B, but not MAO-A (n.s.), in this tissue, but rilmenidine did not inhibit [3H]RO41-1049 or [3H]RO19-6327 binding. The distribution of [3H]2-BFI-labelled I2-RBS overlapped the combined distributions of both MAO-A and -B isoenzymes, suggesting that [3H]2-BFI may label sites on both enzymes in the rabbit, but [3H]2-BFI binding only correlated with [3H]RO19-6327 (r = 0.84, P = 0.07), not [3H]RO41-1049 binding (n.s.). Moreover, 2-BFI only inhibited [3H]RO19-6327, not [3H]RO41-1049 binding. These data are consistent with reports that I2-RBS are located on MAO-B and allosterically influence the catalytic site. The relationship of [3H]rilmenidine- and [3H]2-BFI-labelled I-RBS and the identity of non-MAO-associated [3H]rilmenidine-labelled I-RBS requires further investigation.

Radiopacity of elastomeric impression materials.

The purpose of this study was to measure and classify the radiopacity of various elastomeric impression materials available on the open market and to compare their appearance in radiographs of the oral tissues. In order to measure and classify their radiopacity, twenty-eight specimens of various materials were placed and exposed on film together with an aluminium stepwedge. A dummy head was used to investigate the radiographic density of the above specimens in comparison with that of simulated oral tissues.

Partial agonist activity of celiprolol.

Celiprolol given intravenously (i.v.) to pithed rats in the dose range of 0.1-10,000 micrograms/g produced a dose-dependent increase in heart rate (HR) which was greatest (123 beats/min) at 1,000-3,000 micrograms/kg. This partial agonist effect was blocked by the selective beta 1-adrenoceptor antagonist CGP 20712A. Celiprolol also produced a vasodepressor effect in this dose range which was abolished by the relatively selective beta 2-adrenoceptor antagonist ICI 118551 but not CGP 20712A. The magnitude of this intrinsic sympathomimetic activity (ISA) response was not significantly altered by reserpine pretreatment. Celiprolol also antagonised the effects of isoprenaline 0.05 microgram/kg on HR and blood pressure (BP). The beta 1 selectivity of celiprolol as an antagonist in pithed rats (beta 1/beta 2 = 340:1) was similar to that observed in studies with isolated guinea pig atria and trachea (beta 1/beta 2 = 63:1), both being considerably greater than that observed with atenolol. Celiprolol, however, like atenolol, potentiated the bronchoconstrictor responses to histamine (3 micrograms/kg). Metabolic studies of rats and human urine failed to show significant amounts of potentially vasoactive metabolites. These data are consistent with celiprolol acting as both a beta 1- and beta 2- adrenoceptor partial agonist.

Computer-aided mapping of the beta-adrenoceptor. 1. Explanation for effect of para substitution on blocking activity at the beta-1-adrenoceptor.

Anomalously low affinities for the beta-1-adrenoceptor are seen for members of a series of para-substituted N-isopropylphenoxypropanolamines in which the substituent is able to conjugate with the aromatic ring. The energy of conjugation was calculated using the AM1 semiempirical molecular orbital method and appears to correlate with the loss of binding energy, and hence affinity for the receptor. This suggests that binding is associated with movement of the substituent out of the plane of the aromatic ring due to steric interference with the receptor. A previously unrecognized binding site for aromatic groups off the para position is also identified.

Dry socket: frequency of occurrence after intraligamentary anesthesia.

To determine whether the use of intraligamentary anesthesia increases the incidence of dry socket, results of 305 extractions of mandibular molars in two groups of patients were studied. In the first group, inferior alveolar nerve block was applied, and, in the second, intraligamentary anesthesia was applied. A solution of 2% lidocaine with 1:80,000 epinephrine was used. Statistical analysis of the postoperative occurrence of dry socket indicated that the use of intraligamentary anesthesia did not result in a higher frequency of dry socket than did conventional anesthesia.

[Histiocytosis X: roentgenological findings in 23 cases]. / Histiozytosis X: Röntgenologische Beobachtungen an 23 Fällen.

The authors describe the clinical, roentgenological findings, especially the oral manifestation and differential diagnosis of histiocytosis X in 23 cases. It is shown that the clinical and roentgenological differential diagnosis is problematically.

[Clinical and roentgenographic follow-up study of tricalcium phosphate ceramic in bone cavities of apicoectomized teeth]. / Klinike kai aktinographike melete tes exelixes tes akrorrhizektomes me plerose tes ostikes koilotetas me keramiko phosphoriko triasbestio.

In 8 patients aged 16-30 years with periapical osteolytic areas (1,5-2 cm) of anterior maxillary and mandibular teeth root canal treatment and apicoectomy were performed. The bone cavity following apicoectomy was filled with tricalcium phosphate ceramic (small spheres diameter more than 1 mm and less than 2 mm). Patients were re-examined the following day as well as on the 4th, 7th, and 15th postoperative day. Follow up at the 1, 3, 6, 12 and 18 postoperative months did not show any problem of the healed wood nor any rejection of the implanted material. Radiographically, some resorption of the material as well as new bone formation were noticed 12 and 18 month after the operation.

Biliary excretion and conjugation of diacid angiotensin-converting enzyme inhibitors.

The metabolism and biliary excretion of the diacid angiotensin-converting enzyme inhibitors enalapril, lisinopril, perindopril and ramipril have been studied in an isolated perfused rat liver model. Inhibitors were presented to the livers at a dose of 100 micrograms. The hepatic clearance of lisinopril was very low (0.072 ml/min) and was hardly excreted into the bile. The clearances of enalapril, perindopril and ramipril were higher at 0.63, 0.87 and 9.9 ml/min, respectively, and were excreted into bile. The amounts of ester prodrugs excreted in bile were 4.0, 6.1 and 14%, respectively, whereas the diacid forms were excreted to the extent of 46, 27 and 71% of the administered dose, respectively, over 4 hr. Glucuronide metabolites were only detected in bile in significant concentrations for perindopril and ramipril. Base hydrolysis of the perfusate samples showed that lisinopril was not significantly metabolized to conjugates and that little metabolism of enalapril occurred other than rapid conversion to the diacid form. However, both perindopril and ramipril were extensively metabolized beyond the diacid form. These differences in hepatic handling can in part be explained by their octanol-buffer partition coefficients but may also be related to the introduction of a bicyclic ring in perindopril and ramipril which increases their ability to be metabolized and excreted into bile. These differences in hepatic handling of angiotensin-converting enzyme are likely to influence their clinical usefulness, particularly in renal and hepatic disease.

[Arterial pressure variation following an intravenous and submucous injection of local anaesthetic solutions with vasoconstrictor]. / Metaboles tes arteriakes pieses ystera apo endophlebia kai ypoblennogonia egchyse topikon anaisthetikon dialymaton me aggeiosyspastiko.

This paper deals with the control, registration and statistical evaluation of blood pressure variations (systolic, diastolic and average) after an i.v. and submucous injection of fixed quantity local anaesthetic solutions (0.05 ml) in white hamsters. The solutions used were: lidocaine 2% with adrenaline 1/80,000, lidocaine 3% with noradrenaline 1/25,000. The intravenous injection of all three local anaesthetic solutions has caused an increase of the arterial pressure parameters which was statistically significant (P less than 0.01). The submucous injection of lidocaine 2% solution with adrenaline 1/80,000 and lidocaine 2% with noradrenaline 1/80,000 has not caused mentionworthy arterial pressure variations. On the contrary, the submucous injection of lidocaine 3% solution with noradrenaline 1/25,000 has led to an increase of the arterial pressure which is statistically important (P less than 0.05). The research results have led to the following conclusions: 1) Intravascular injection of local anaesthetics with adrenaline or noradrenaline has immediate negative consequences on the circulatory system, a fact which renders necessary a test respiration prior to any stem anaesthesia. 2) The submucous injection of lidocaine solutions with adrenaline or noradrenaline 1/80,000 may be described as harmless with respect to cardiovascular toxicity, and 3) The 3% lidocaine solution with noradrenaline 1/25,000 has proved to be capable of producing significant increase of the arterial pressure following a submucous injection. Anaesthetic solutions with 1/25,000 noradrenaline concentration should not be used, while they must be considered as extremely hazardous for patients with cardiovascular problems.

Biotransformation studies of di-acid angiotensin converting enzyme inhibitors.

The biotransformation of di-acid angiotensin converting enzyme inhibitors (I) to cyclized lactam metabolites was studied in the urine of rats using gas chromatography-mass spectrometry. Chemical synthesis of the corresponding piperazine-dione metabolite (III) was achieved by reaction of enalapril, perindopril or ramipril with acetic acid anhydride followed by hydrolysis of the ester group by sodium in ethanol or by acid hydrolysis. Electron impact and chemical ionization mass spectra confirmed the structure of these potential novel metabolites. Selected ion monitoring of urinary extracts demonstrated small amounts (less than 5%) of these lactams for all three inhibitors, however, it was shown that the majority of these lactams were formed as a result of sample treatment rather than due to biotransformation.