Miracle-dz/UniFAR-FTUs huggingface dataset:
[Permanent atrial resynchronization by synchronous bi-atrial pacing in the preventive treatment of atrial flutter associated with high degree interatrial block].

UNLABELLED Interatrial conduction block results in a very delayed and retrograde activation of the left atrium and is associated with a high incidence of atrial tachyarrhythmias, especially a particular (and specific) form of atypical atrial flutter. Electrophysiologic studies have suggested that these arrhythmias were usually due to reentry and could be directly related to the conduction disturbances in the atrium. If so, we can expect reasonably that permanent atrial resynchronization resulting from simultaneous pacing in different target sites in the atria, may not only correct for interatrial dysynchrony, but also may significantly contribute to prevent arrhythmia recurrences. Twenty-eight patients, mean age 68 years, were included. The mean P wave duration in spontaneous sinus rhythm was 181 +/- 28 ms. In all patients, many recurrences of atrial tachyarrhythmia were documented, especially a specific form of atypical atrial flutter. Medical therapy was constantly ineffective. Three different pacing modes were used: 6 patients, with normal A-V conduction were implanted with a SSI device, programmed in AAT mode and connected, using a Y bifurcated connector, to two atrial leads, one positioned in the right atrium, the second one into the coronary sinus-in 14 patients, with A-V conduction defects, a conventional DDDR unit was implanted and connected to a composite biatrial electrode and a ventricular lead. In that configuration atrial resynchronization was only effective on paced atrial cycles -a specific DDD Chorus ELA Medical device with a special algorithm loaded into the RAM memory was implanted in 14 patients (8 new indications, and 6 patients first implanted with a DDDR unit). RESULTS during sinus rhythm atrial resynchronization induced a reduction of the P wave duration from 181 +/- 28 ms to 116 +/- 12 ms. During permanent pacing the mean value decreased from 209 +/- 38 ms to 108 +/- 13 ms. During follow-up (34 +/- 15 months) arrhythmia prevention was assessed by history, by monthly surface ECG's and by bimonthly 24 hours Holters recordings and telemetric interrogation of the pacemaker statistics. Twenty-one patients did not experienced any recurrence of arrhythmia. One to three recurrences occurred in the other seven patients, including six patients implanted with a conventional DDDR unit. These preliminary results seem validate the new concept of atrial resynchronization for prevention of atrial arrhythmia associated with interatrial conduction block.
Renal Insufficiency Following Radiocontrast Exposure Trial (REINFORCE): a randomized comparison of sodium bicarbonate versus sodium chloride hydration for the prevention of contrast-induced nephropathy

IntroductionFor the prevention of contrast-induced nephropathy (CIN) after coronary angiography, hydration by 0.9% sodium chloride solution and N-acetylcysteine is currently recommended. However, it is unclear whether volume supplementation with sodium bicarbonate is better than with sodium chloride when used in conjunction with nonionic, low-osmolar iopamidol. The aim of this study was to analyze and compare the effects of sodium bicarbonate and sodium chloride on renal function in 145 patients exposed to nonionic iso-osmolar contrast medium iodixanol in a randomized study. Patients and methodsRenal Insufficiency Following Radiocontrast Exposure is a prospective, randomized, single-center, double-blinded trial of 145 patients (age 72.6±6.7 years) with elevated baseline serum creatinine levels (mean 132.6±29.3 μmol/l). Eligible patients were randomized to either a 154 mEq/l infusion of sodium bicarbonate (n=71, group I) or sodium chloride 0.9% solution (n=74, group II). The primary endpoint was serum creatinine elevation beyond 25% or 44 μmol/l on the first or second day following exposure to the contrast medium. Serum creatinine, serum cystatin C, plasma viscosity, urinary enzymes alanine aminopeptidase and N-acetyl-&bgr;-D-glucosaminidase, and &agr;1-microglobulin were measured at baseline and on days 1 and 2 after contrast medium administration. ResultsAn overall proportion of five CIN (3.4%) was observed with equal distribution among the groups (4.2% in sodium bicarbonate group vs. 2.7% in sodium chloride group; P=0.614). Parameters of renal function demonstrated no differences between the two hydration regimens on day 1 after angiography; even on day 2 most parameters were similar in groups I and II. ConclusionRenal Insufficiency Following Radiocontrast Exposure demonstrates a homogeneously low rate of CIN after exposure to nonionic, iso-osmolar iodixanol regardless of the use of either bicarbonate sodium or sodium chloride solution for volume supplementation. Low-toxicity contrast media and any hydration may offset potential antioxidant effects of sodium bicarbonate.
Drug‐Induced Up‐Regulation of Dopamine D2 Receptors on Cultured Cells

Abstract: Ligand‐induced up‐regulation of recombinant dopamine D2 receptors was assessed using C6 glioma cells stably expressing the short (415‐amino‐acid; D2S) and long (444‐amino‐acid; D2L) forms of the receptor. Overnight treatment of C6‐D2L cells with N‐propylnorapomorphine (NPA) caused a time‐ and concentration‐dependent increase in the density of receptors, as assessed by the binding of radioligand to membranes prepared from the cells, with no change in the affinity of the receptors for the radioligand. The effect of 10 µM NPA was maximal after 10 h, at which time the density of D2L receptors was more than doubled. The agonists dopamine and quinpirole also increased the density of D2L receptors. The receptor up‐regulation was not specific for agonists, because the antagonists epidepride, sulpiride, and domperidone caused smaller (30–60%) increases in receptor density. Prolonged treatment with 10 µM NPA desensitized D2L receptors, as evidenced by a reduced ability of dopamine to inhibit adenylyl cyclase, whereas treatment with sulpiride was associated with an enhanced responsiveness to dopamine. The magnitude of NPA‐induced receptor up‐regulation in each of four clonal lines of C6‐D2L cells (mean increase, 80%) was greater than in all four lines of C6‐D2S cells (33%). Inactivation of pertussis toxin‐sensitive G proteins had no effect on the basal density of D2L receptors or on the NPA‐induced receptor up‐regulation. Treatment with 5 µg/ml of cycloheximide, on the other hand, decreased the basal density of receptors and attenuated, but did not prevent, the NPA‐induced increase. Chimeric D1/D2 receptors were used to identify structural determinants of dopamine receptor regulation. Treatment with the D1/D2 agonist NPA decreased the density of D1 and chimeric CH4 and CH3 receptors. The latter two receptors have D1 sequence from the amino‐terminus to the amino‐terminal end of transmembrane region (TM) VII and VI, respectively. CH2, with D1 sequence up to the amino‐terminal end of TM V, and thus the third cytoplasmic loop of the D2 receptor, was up‐regulated by NPA or the D2‐selective agonist quinpirole. Quinpirole treatment decreased the density of CH3 and had no effect on CH4 or D1 receptors. The different responses of CH2 and CH3 to agonist treatment suggest a role for TM V and the third cytoplasmic loop in the direction of receptor regulation.
Skeletal muscle metabolism in the leg during exercise in patients with congestive heart failure.

1. Using 31P nuclear magnetic resonance, it has previously been demonstrated that patients with congestive heart failure exhibit a greater than normal phosphocreatine (PCr) depletion in the working skeletal muscles of the arm. We have studied the importance of the work necessary to reach a similar PCr depletion ([PCr]/([PCr] + [Pi]) = 0.5) in calf muscle. Our results show significantly lower values for patients with congestive heart failure in both aerobic and ischaemic conditions (respectively: 0.009 +/- 0.007 vs 0.026 +/- 0.013 W/kg body weight, P less than 0.01; 0.29 +/- 0.16 vs 0.90 +/- 0.25 J/kg body weight, P less than 0.01). 2. This original model of skeletal muscle exercise facilitates a comparison of PCr recovery rate due to a similarity in the PCr depletion and intracellular pH in the two series at the start of recovery. However, the PCr recovery rate is similar after both normoxic and ischaemic exercise, i.e. respective percentages of PCr increase in the first 25 s recovery spectrum were: (a) aerobic exercise, congestive heart failure 133 +/- 18%, control series 138 +/- 18%; (b) ischaemic exercise, congestive heart failure 114 +/- 13%, control series 118 +/- 12%. The absence of a difference in PCr recovery rate and the greater PCr depletion by ischaemic work in patients with congestive heart failure suggest modifications that cannot be explained by a reduced blood flow to the muscle. 3. When comparing the two series, intracellular pH evolved similarly in normoxia and ischaemia during both work and recovery. Thus, no increase in anaerobic glycolytic activity appears when equivalent PCr depletion has occurred.
KGF and BMP‐6 intervene in cellular reprogramming and in mesenchymal‐epithelial transition (MET) of 3T3L1 mouse adipose cells

Mesenchymal‐epithelial transition (MET) is an inevitable process for cellular reprogramming. MET could be induced by suppressing epithelial‐mesenchymal transition (EMT) signaling and activating an epithelial program within the cells. Aiming at MET, we investigated the potential of keratinocyte growth factor (KGF) and bone morphogenetic protein (BMP)‐6 separately for the induction of MET in 3T3L1 mouse adipose cells and to trace the molecular events that probably upregulate during MET induction. KGF successfully induced MET through upregulation of epithelial related genes and transcript expression on 3T3L1 cells. In contrast, BMP‐6 plays completely the reverse role through downregulation of all epithelial related genes and transcript expression. In KGF based treatment, seven genes (K8, K18, EpCAM, K5, K14, SMN1 and α‐SMA) out of a total of eight genes were significantly (P < 0.05/P < 0.01) upregulated. Immunostaining and immunoblotting also revealed significant (P < 0.05/P < 0.01) expression of several epithelial‐specific surface antigens and transcripts. Moreover, Ayoub Shaklar staining (specific to keratin) of KGF treated cells showed formation of keratin (reddish brown color) within cytoplasm of the cells, whereas control and BMP‐6 treated cells did not. Conclusively, KGF was observed to have the potential to enhance MET and these clues could be used in future research into cellular reprogramming and regenerative medicine.
On the efficient segmentation of network links

The Internet is experiencing a change in paradigm: once determined by text-based applications, currently, various types of audio-visual content already adopt the major part of the bandwidth. Audio-visual applications and multimedia data impose individual demands on reliability and delivery time, which are not sufficiently covered by available transport protocols. In addition, a more efficient use of network resources such as link bandwidth or the spatial distribution of network routes is essential. Therefore, a split of a given transmission path into several independent areas, where each contains a set of similar, adjacent network links is appropriate. An individual transmission and error correction scheme can be applied to such a group of related links. In previous work it has been shown that there is an optimum number of segments. Too few or too many limit the achievable efficiency, i.e. increase the required redundancy information. The search for this optimum, however, is a complex task not applicable to real-time adaptivity. This paper proposes a decentralized, metric based mechanisms to decide where a network path should be intersected, leading to a lower complexity for the retrieval of these areas. We also investigate an example where the proposed clustering approach leads to an overall redundancy information of about 1/4 of the redundancy information obtained by a traditional end-to-end approach and thus is very close to the Shannon limit.
Rôle de l'activité dépendante du calcium au cours du développement et de la maturation des neurones ganglionnaires vestibulaires de souris

Le calcium est un element indispensable a la formation du systeme nerveux. Il intervient dans de nombreuses fonctions qui permettent la mise ne place et le fonctionnement d'un organe. Le but de ce travail a ete de caracteriser les canaux calciques de type T dependants du potentiel presents transitoirement dans les neurones vestibulaires primaires et de comprendre le role des influx calciques qu'ils induisent au cours du developpement perinatal chez la souris. Grâce a des etudes electrophysiologiques et pharmacologiques nous avons caracterise les proprietes des sous-unites du canal de type T, Cav3.1 et Cav3.2, cette derniere generant un courant de forte amplitude a un stade precoce du developpement. L'etude de l'activite electrique de ces neurones revele la presence d'une depolarisation post potentiel correlee avec l'expression du canal Cav3.2. L'analyse des proprietes de l'activite electrique aux stades precoces du developpement revele qu'elle presente un ralentissement de la phase de repolarisation du potentiel d'action bloque par le cadmium. Cette activite devient plus rapide aux stades plus matures. Ces observations ont ete faites a des stades de developpement ou se deroulent la neuritogenese et la synaptogenese. Nous avons pu determiner le role physiologique de Cav3.2 et de l'activite electrique qui decoule de son activation par l'utilisation d'antisens sur un modele de culture de neurones. En l'absence de ces dernieres, un ralentissement de la pousse neuritique a ete observe, demontrant l'implication cruciale des courants calciques de type T dans la formation de ce systeme sensoriel.
Regional cerebral blood flow: studies in the fetal lamb during hypoxia, hypercapnia, acidosis, and hypotension.

In order to determine the relative roles of O2 tension and content, CO2 tension, hydrogen ion concentration, arterial blood pressure, and cardiac output in the regulation of fetal cerebral blood flow (CBF), we used radioactively labeled microspheres to measure flow to 20 major brain regions in 24 chronically catheterized fetal lambs. We continually monitored fetal heart rate and blood pressure, and periodically measured arterial PO2, PCO2, pH, and hematocrit. In addition to CBF measurements during control periods, we measured CBF during: 1) hypoxia (O2 content less than 6 ml X dl-1; O2 tension less than 15 torr) induced by having the ewe breathe a gas mixture with low O2 concentration, 2) hypercapnia (PCO2 greater than 50 torr) induced by increasing the maternal inspired CO2, 3) acidosis and alkalosis (7.60 greater than pH greater than 6.60) induced by infusing lactic acid or bicarbonate into the fetus, and 4) hypotension (blood pressure less than 35 mm Hg) and hypertension (blood pressure greater than 55 mm Hg) induced by rapidly phlebotomizing or transfusing the fetus. We used multiple regression analysis and analysis of covariance to examine the dependence of total cerebral blood flow on arterial O2 tension and content, CO2 tension, pH, blood pressure, and cardiac output. (ABSTRACT TRUNCATED AT 250 WORDS)
What are the reasons for negative phase III trials of molecular‐target‐based drugs?

The results of molecular‐biological studies of cancer are changing the way we diagnose and treat cancer. Target‐based drug discovery selects agents for development based on their mechanisms of action. The interaction between target‐based drugs and their targets can be described by classical drug‐receptor theory. Clinical trials have demonstrated that some effective target‐based drugs induce apoptosis, even though they are considered to be cyto‐static. Numerous phase III trials of target‐based drugs have been conducted. Although some have yielded strongly positive results, the majority of the results have been negative. This article seeks to clarify the value of molecular‐target‐based therapy and to discuss the reasons for negative results in phase III trials. The importance of proof‐of‐principle studies is stressed throughout preclinical and clinical trials of molecular‐target‐based drugs.
Potential contribution of computer-aided detection to the sensitivity of screening mammography.

PURPOSE To determine the false-negative rate in screening mammography, the capability of computer-aided detection (CAD) to identify these missed lesions, and whether or not CAD increases the radiologists' recall rate. MATERIALS AND METHODS All available screening mammograms that led to the detection of biopsy-proved cancer (n = 1,083) and the most recent corresponding prior mammograms (n = 427) were collected from 13 facilities. Panels of radiologists evaluated the retrospectively visible prior mammograms by means of blinded review. All mammograms were analyzed by a CAD system that marks features associated with cancer. The recall rates of 14 radiologists were prospectively measured before and after installation of the CAD system. RESULTS At retrospective review, 67% (286 of 427) of screening mammography-detected breast cancers were visible on the prior mammograms. At independent, blinded review by panels of radiologists, 27% (115 of 427) were interpreted as warranting recall on the basis of a statistical evaluation index; and the CAD system correctly marked 77% (89 of 115) of these cases. The original attending radiologists' sensitivity was 79% (427 of [427 + 115]). There was no statistically significant increase in the radiologists' recall rate when comparing the values before (8.3%) with those after (7.6%) installation of the CAD system. CONCLUSION The original attending radiologists had a false-negative rate of 21% (115 of [427 + 115]). CAD prompting could have potentially helped reduce this false-negative rate by 77% (89 of 115) without an increase in the recall rate.
A portable impedance biosensor instrument for rapid detection of avian influenza virus

The objectives of this study were to improve our previous portable impedance biosensor instrument with more rapid, reliable and quantitative features for detection of avian influenza (AI) virus and to evaluate its performance using H5N1 and H5N2 virus. A high-intensity and high-gradient magnetic field based separator was designed and fabricated for rapid separation of AI virus. KPL measuring solution was used as background medium to obtain higher stability. Twin BNC connection between the electronic circuit and the biochip was employed to prevent radio frequency interference. The amplitude limiting average filtering method was used to eliminate false signals and a linear regression model was built for the embedded control software. A data acquisition software was developed for communication and data processing. This impedance biosensor instrument could work stand-alone or be connected with a laptop via USB interface. The experimental results showed that the impedance biosensor could identify H5N1 virus with a detection limit of 103 EID50/mL in 30 min. A prototype of the improved impedance biosensor was fabricated for evaluation with cloacal swab samples from AI H5N2 virus infected chickens. Compared with viral isolation, this biosensor instrument had a false negative rate of 10%, whereas realtime RT-PCR showed a false negative/positive rate of 20%.
Operant Conditioning of Spinal Stretch Reflexes in Patients with Spinal Cord Injuries

Hyperactive spinal stretch reflexes (SSRs) often occur with spinal cord injuries (SCI). These altered SSRs may impair movement. Recent studies in monkeys and human subjects have indicated that the magnitude of SSRs can be modulated using operant conditioning. The purpose of this study was to determine whether hyperactive biceps brachii SSRs could be operantly conditioned downward. Seventeen chronic (> 1 year postlesion) spinal cord-injured patients participated. Subjects were trained to keep biceps background (prestretch) electromyographic (EMG) activity and elbow angle at predetermined levels prior to having the elbow rapidly extended by a torque motor to elicit the biceps SSR. All subjects participated in six baseline sessions over a 2-week period. Then, subjects were randomly assigned to either control or training groups for the next 24 sessions over an 8-week period. By the end of the study, training subjects had significantly reduced biceps SSRs (t test, P < 0.001), while control subjects SSRs were not significantly reduced (t test, P > 0.05). The reduced SSRs persisted for up to 4 months following cessation of training. The results of this study support the hypothesis that hyperactive SSRs can be operantly conditioned downward in SCI patients.
Substance P-Fibronectin-Cytokine Interactions in Myeloproliferative Disorders with Bone Marrow Fibrosis

Bone marrow (BM) fibrosis could occur secondarily to several clinical disorders: hematological and nonhematological. Clinical presentation of fibrosis could occur in myeloproliferative diseases, lymphoma, myelodysplastic syndrome and myeloma. The pathophysiology underlying BM fibrosis remains unclear despite intensive study, with a corresponding lack of specific therapy. This review discusses new insights in the role of substance P, cytokines and fibronectin in the development of BM fibrosis. Substance P is a neuropeptide that possesses pleiotropic properties, e.g. neurotransmission and immune/hematopoietic modulation and is linked to BM fibrosis. Cytokines and growth factors, in particular those associated with fibrogenic properties, e.g. TGF-β, IL-1 and platelet-derived growth factor, are linked to BM fibrosis. Extracellular matrix proteins are increased in patients with BM fibrosis. Fibronectin in the sera of patients with BM fibrosis is complexed to substance P. Fibronectin appears to protect substance P from degradation by endogenous peptidases. This review describes the preliminary findings on the colocalization of substance P and fibronectin in the BM of patients with fibrosis. These data are reviewed in the context of published reports with particular focus on the relevant cytokines. A more detailed understanding of intra- and intercellular mechanisms in BM fibrosis may lead to effective therapy.
Étude des couples chimiokines/récepteurs comme nouvelles cibles thérapeutiques des cancers colorectaux métastasés : études précliniques

Avec 42 000 nouveaux cas diagnostiques en 2012, le cancer colorectal (CCR) represente en France le troisieme cancer en termes d’incidence. Les metastases, qui surviennent principalement au niveau du foie et des poumons, en constituent la principale cause de deces. Malgre les progres recents de la chimiotherapie et des agents cibles, le taux de survie a 5 ans des patients presentant un CCR metastase reste faible. Aujourd’hui, la resection chirurgicale est le seul traitement curatif, cependant moins de 20% des patients porteurs de metastases sont operables. Il existe donc un grand nombre de patients presentant un CCR metastase pour lequel aucun traitement curatif ne peut etre propose. La formation des metastases a partir d’une tumeur primaire resulte d’une longue serie d’etapes sequentielles liees les unes aux autres. L’issue de ce processus depend a la fois des proprietes intrinseques des cellules tumorales et de la reponse de l’hote. Il a recemment ete montre que les couples chimiokines/recepteurs interviennent dans le controle des differentes etapes de la progression tumorale.Le projet de recherche developpe au cours de mon travail de these avait pour objectif d’utiliser les chimiokines et leurs recepteurs dans de nouvelles strategies therapeutiques pour bloquer et/ou eradiquer les metastases hepatiques et pulmonaires des CCRs. Le travail s’est articule selon deux axes dans lesquels nous avons montre d’une part que, le blocage du recepteur de chimiokines CXCR7 permet de limiter les metastases pulmonaires de CCRs et d’autre part que, le transfert de gene codant CX3CL1 au niveau du foie entraine une reponse anti-tumorale efficace dans les metastases hepatiques de CCRs.