Once escaped from the quiescence niche, precursor cells interact with stromal components that support their survival, proliferation, and differentiation. We examined interplays between human myogenic ...precursor cells (mpc) and monocyte/macrophages (MP), the main stromal cell type observed at site of muscle regeneration. mpc selectively and specifically attracted monocytes in vitro after their release from quiescence, chemotaxis declining with differentiation. A DNA macroarry-based strategy identified five chemotactic factors accounting for 77% of chemotaxis: MP-derived chemokine, monocyte chemoattractant protein-1, fractalkine, VEGF, and the urokinase system. MP showed lower constitutive chemotactic activity than mpc, but attracted monocytes much strongly than mpc upon cross-stimulation, suggesting mpc-induced and predominantly MP-supported amplification of monocyte recruitment. Determination of 3 Hthymidine incorporation, oligosomal DNA levels and annexin-V binding showed that MP stimulate mpc proliferation by soluble factors, and rescue mpc from apoptosis by direct contacts. We conclude that once activated, mpc, which are located close by capillaries, initiate monocyte recruitment and interplay with MP to amplify chemotaxis and enhance muscle growth.
Macrophagic myofasciitis (MMF) is an emerging condition of unknown cause, detected in patients with diffuse arthromyalgias and fatigue, and characterized by muscle infiltration by granular periodic ...acid–Schiff's reagent-positive macrophages and lymphocytes. Intracytoplasmic inclusions have been observed in macrophages of some patients. To assess their significance, electron microscopy was performed in 40 consecutive cases and chemical analysis was done by microanalysis and atomic absorption spectrometry. Inclusions were constantly detected and corresponded to aluminium hydroxide, an immunostimulatory compound frequently used as a vaccine adjuvant. A lymphocytic component was constantly observed in MMF lesions. Serological tests were compatible with exposure to aluminium hydroxide-containing vaccines. History analysis revealed that 50 out of 50 patients had received vaccines against hepatitis B virus (86%), hepatitis A virus (19%) or tetanus toxoid (58%), 3–96 months (median 36 months) before biopsy. Diffuse myalgias were more frequent in patients with than without an MMF lesion at deltoid muscle biopsy (P < 0.0001). Myalgia onset was subsequent to the vaccination (median 11 months) in 94% of patients. MMF lesion was experimentally reproduced in rats. We conclude that the MMF lesion is secondary to intramuscular injection of aluminium hydroxide-containing vaccines, shows both long-term persistence of aluminium hydroxide and an ongoing local immune reaction, and is detected in patients with systemic symptoms which appeared subsequently to vaccination.
Abstract Background Objective pain assessment that is not subject to influences from either cultural or comprehension issues is desirable. Analysis of heart rate variability has been proposed as a ...potential method. This pilot study aimed to assess the performance of the PhysioDoloris™ analgesia monitor which calculates an Analgesia Nociception Index derived from heart rate variability. It was compared with visual analogical pain scores. Methods Forty-five parturients who requested epidural analgesia were recruited. Simultaneous couplets of pain scores and Analgesia Nociception Index values were recorded every 5 min regardless of the presence or absence of uterine contractions. The relationship between indices was characterized, and a cut-off value of Analgesia Nociception Index corresponding to a visual analogical score >30 (range 0–100) was used to determine the positive and negative predictive value of the Analgesia Nociception Index. Results There was a negative linear relationship between visual analogical pain scores and Analgesia Nociception Index values regardless of the presence of uterine contractions (regression coefficient ± SEM = −0.18 ± 0.032 for entire dataset). Uterine contraction significantly reduced the Analgesia Nociception Index ( P < 0.0001). Using a visual analogical pain score >30 to define a painful sensation, the lower 95% confidence limit for the Analgesia Nociception Index score was 49. Conclusion The Analgesia Nociception Index has an inverse linear relationship with visual analogical pain scores. Further studies are necessary to confirm the results of this pilot study and to look at the influence of epidural analgesia on the Analgesia Nociception Index.
Abstract The literature suggests that misoprostol can be offered to patients for off-label use as it has reasonable efficacy, risk/benefit ratio, tolerance and patient satisfaction, according to the ...criteria for evidence-based medicine. Both the vaginal and sublingual routes are more effective than the oral route for first-trimester cervical dilatation. Vaginal misoprostol 800 μg, repeated if necessary after 24 or 48 h, is a possible alternative for management after early pregnancy failure. However, misoprostol has not been demonstrated to be useful for the evacuation of an incomplete miscarriage, except for cervical dilatation before vacuum aspiration. Oral mifepristone 200 mg, followed 24–48 h later by vaginal, sublingual or buccal misoprostol 800 μg (followed 3–4 h later, if necessary, by misoprostol 400 μg) is a less efficacious but less aggressive alternative to vacuum aspiration for elective or medically-indicated first-trimester terminations; this alternative becomes increasingly less effective as gestational age increases. In the second trimester, vaginal misoprostol 800–2400 μg in 24 h, 24–48 h after at least 200 mg of mifepristone, is an alternative to surgery, sulprostone and gemeprost. Data for the third trimester are sparse. For women with an unripe cervix and an unscarred uterus, vaginal misoprostol 25 μg every 3–6 h is an alternative to prostaglandin E2 for cervical ripening at term for a live fetus. When oxytocin is unavailable, misoprostol can be used after delivery for prevention (sublingual misoprostol 600 μg) and treatment (sublingual misoprostol 800 μg) of postpartum haemorrhage. The use of misoprostol to promote cervical dilatation before diagnostic hysteroscopy or surgical procedures is beneficial for premenopausal women but not for postmenopausal women. Nonetheless, in view of the side effects of misoprostol, its use as a first-line treatment is not indicated, and it should be reserved for difficult cases. Misoprostol is not useful for placing or removing the types of intra-uterine devices used in Europe, regardless of parity.
Breakdown of the blood–brain barrier (BBB) and ensuing gliosis are common events following physical trauma to the central nervous system (CNS) or during autoimmune diseases such as experimental ...allergic encephalomyelitis (EAE). Some studies of EAE in rodents report that peripheral injections of complete Freund's adjuvant (CFA), which contains heat-inactivated Mycobacterium to provoke peripheral inflammation without adversely affecting the CNS, can itself lead to increased BBB permeability to small tracer molecules and certain serum proteins. To study the equivocal relationship between serum protein extravasation and reactive gliosis, we injected C57BL/6 mice with CFA and histologically assessed the permeability of various serum proteins and the reactivity of proximal microglia and astrocytes in the uninjured brainstem and spinal cord enlargements after 1–4 weeks. Our results confirm that CFA injections induce progressive increases in the perivascular extravasation of serum IgG, albumin, IgM, and exogenous horseradish peroxidase, all to varying degrees, most prominently in the brainstem and cervical spinal cord after 2–3 weeks. More importantly, neither microglial cells nor astrocytes in regions of focal serum protein leakage appeared morphologically reactive based on immunoreactivity for CR3 receptors (Mac-1) or glial fibrillary acidic protein (GFAP), respectively. Because we found no evidence of T cell infiltration accompanying the exudates, our results indicate that in the absence of physical trauma or inflammatory cells resident CNS neuroglia remain quiescent upon exposure to extravasated serum proteins.
Abstract
Background
Tricuspid regurgitation (TR) is frequent among patients with severe left-sided valvular heart disease (LS-VHD).
Objectives
This study sought to assess TR frequency, management and ...outcome in this population.
Methods
Among 6883 patients with severe LS-VHD or previous valvular intervention in the EURObservational Research Programme prospective VHD II survey, we analyzed frequency and grade of TR according to LS-VHD, and 6-month survival according to TR grade. Among 2081 patients who underwent an intervention for severe LS-VHD, we analyzed frequency and outcome of concomitant TV intervention, and concordance between Class I indications for concomitant TV surgery (patients with severe TR) and real-practice decision-making.
Results
Moderate to severe TR was very frequent among patients with severe mitral VHD (≥30%), especially in patients with secondary mitral regurgitation (46%), and rare among patients with aortic VHD (<5%). Higher TR grade was associated with a poorer 6-month survival (P<0.001). Rates of concomitant tricuspid valve (TV) intervention at the time of left-sided heart valve surgery were high at the time of mitral valve surgery (more than 40%). Concomitant TV intervention at the time of left-sided heart valve surgery (LS-HVS) was not associated with an increase in-hospital mortality (P=0.93). Concordance between Class I indications for concomitant TV surgery at the time of LS-HVS according to guidelines and real-practice decision-making was very good (88% overall).
Conclusion
TR was frequent in patients with mitral VHD and was associated with a poorer outcome as TR grade increased. Compliance to guidelines for Class I indications for concomitant TV surgery at the time of LS-HVS was very good. With the trend toward more transcatheter treatment for left-sided VHD, there is a critical need for safe and efficient tricuspid valve transcatheter treatment for patients with concomitant TR.
Funding Acknowledgement
Type of funding sources: None.
The 2016 American Society of Echocardiography (ASE) and European Association of Cardiovascular Imaging (EACVI) guidelines for the evaluation of left ventricular diastolic function reported a new ...algorithm to assess diastolic function and to estimate left ventricular filling pressure (LVFP). At least five to six different parameters were necessary to conclude, each of them with their own inter-observer variability. This article examines the reproducibility of each parameter of the algorithm and its influence on the final decision of the clinician. Echocardiographic exams of 12 non-selected patients without any known cardiac disease or follow-up but addressed to the hospital for symptoms were analyzed by two readers (one junior and one senior) in five French cardiologic tertiary centers. Inter-observer reproducibility at each step of the algorithm and final decision were analyzed. There was mild agreement on the final decision. The main reasons of discrepancy were disagreement on the significance of mitral annular calcifications and measured values that are just around the cut-off (despite good reproducibility, a slight variation could lead to misclassification of a dichotomous choice between a normal measure and a pathologic measure). Without considering performance, this multicentric French study puts forward limits to the actual algorithm recommended for LVFP pattern assessment. Agreement is excellent in caricatural (easy) cases (left ventricular pressure clearly normal or clearly elevated) but a great discordance exists in the gray zone. Improvement in the algorithm and in the method for LVFP determination is proposed.
Actinobacillus pleuropneumoniae is the etiological agent of porcine pleuropneumonia, which causes worldwide severe losses in pig farming. The virulence of the 15 serotypes of
A. pleuropneumoniae is ...mainly determined by the three major RTX toxins ApxI, ApxII and ApxIII, which are secreted by the different serotypes in various combinations. A fourth RTX toxin, ApxIV, is produced by all 15 serotypes only during infection of pigs, but not under in vitro conditions. Pigs infected with
A. pleuropneumoniae show specific antibodies directed against ApxIV. In contrast, antibodies against the other three toxins ApxI, ApxII and ApxIII are also found in pigs free of
A. pleuropneumoniae. The antibodies to the three latter might result from other, less pathogenic
Actinobacillus species such as
A. rossii and
A. suis. We used a recombinant protein based on the N′-terminal part of ApxIV to serologically detect
A. pleuropneumoniae infections in pigs by immunoblot analysis. The analysis of sera of experimentally infected pigs revealed that ApxIV-immunoblots detected
A. pleuropneumoniae infections in the second to third week post infection. We developed an indirect ELISA based on the purified recombinant N′-terminal moiety of ApxIV. The analysis of sera from pigs that were experimentally or naturally infected by
A. pleuropneumoniae, and of sera of pigs that were free of
A. pleuropneumoniae, revealed that the ELISA had a specificity of 100% and a sensitivity of 93.8%. The pre-validation study of the ApxIV-ELISA revealed that the latter was able to detect
A. pleuropneumoniae-positive herds, even when clinical and pathological signs of porcine pleuropneumonia were not evident. Pigs vaccinated with a subunit vaccine Porcilis App™ were serologically negative in the ApxIV-ELISA.
Several prognostic scoring systems have been proposed for chronic myelomonocytic leukemia (CMML), a disease in which some gene mutations-including ASXL1-have been associated with poor prognosis in ...univariable analyses. We developed and validated a prognostic score for overall survival (OS) based on mutational status and standard clinical variables.
We genotyped ASXL1 and up to 18 other genes including epigenetic (TET2, EZH2, IDH1, IDH2, DNMT3A), splicing (SF3B1, SRSF2, ZRSF2, U2AF1), transcription (RUNX1, NPM1, TP53), and signaling (NRAS, KRAS, CBL, JAK2, FLT3) regulators in 312 patients with CMML. Genotypes and clinical variables were included in a multivariable Cox model of OS validated by bootstrapping. A scoring system was developed using regression coefficients from this model.
ASXL1 mutations (P < .0001) and, to a lesser extent, SRSF2 (P = .03), CBL (P = .003), and IDH2 (P = .03) mutations predicted inferior OS in univariable analysis. The retained independent prognostic factors included ASXL1 mutations, age older than 65 years, WBC count greater than 15 ×10(9)/L, platelet count less than 100 ×10(9)/L, and anemia (hemoglobin < 10 g/dL in female patients, < 11g/dL in male patients). The resulting five-parameter prognostic score delineated three groups of patients with median OS not reached, 38.5 months, and 14.4 months, respectively (P < .0001), and was validated in an independent cohort of 165 patients (P < .0001).
A new prognostic score including ASXL1 status, age, hemoglobin, WBC, and platelet counts defines three groups of CMML patients with distinct outcomes. Based on concordance analysis, this score appears more discriminative than those based solely on clinical parameters.
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