Developmental and evolutionary significance of the mandibular arch and prechordal/premandibular cranium in vertebrates: revising the heterotopy scenario of gnathostome jaw evolution

The cephalic neural crest produces streams of migrating cells that populate pharyngeal arches and a more rostral, premandibular domain, to give rise to an extensive ectomesenchyme in the embryonic vertebrate head. The crest cells forming the trigeminal stream are the major source of the craniofacial skeleton; however, there is no clear distinction between the mandibular arch and the premandibular domain in this ectomesenchyme. The question regarding the evolution of the gnathostome jaw is, in part, a question about the differentiation of the mandibular arch, the rostralmost component of the pharynx, and in part a question about the developmental fate of the premandibular domain. We address the developmental definition of the mandibular arch in connection with the developmental origin of the trabeculae, paired cartilaginous elements generally believed to develop in the premandibular domain, and also of enigmatic cartilaginous elements called polar cartilages. Based on comparative embryology, we propose that the mandibular arch ectomesenchyme in gnathostomes can be defined as a Dlx1-positive domain, and that the polar cartilages, which develop from the Dlx1-negative premandibular ectomesenchyme, would represent merely posterior parts of the trabeculae. We also show, in the lamprey embryo, early migration of mandibular arch mesenchyme into the premandibular domain, and propose an updated version of the heterotopy theory on the origin of the jaw.     

An application of a patient-specific cardiac simulator for the prediction of outcomes after mitral valve replacement: a pilot study

Journal of Artificial Organs - Despite advancements in preoperative prediction of patient outcomes, determination of the most appropriate surgical treatments for patients with severely impaired...     

External compression due to seroma of ventricular assist device outflow graft

Journal of Artificial Organs - A 45-year-old woman with repaired complex congenital heart disease, who underwent placement of Jarvik 2000, a ventricular assist device (VAD) for 4 years,...     

Acute surgical unit safely reduces unnecessary after-hours cholecystectomy

Introduction

The acute surgical model has been trialled in several institutions with mixed results. The aim of this study was to determine whether the acute surgical model provides better outcomes for patients with acute biliary presentation, compared with the traditional emergency surgery model of care.

Methods

A retrospective review was carried out of patients who were admitted for management of acute biliary presentation, before and after the establishment of an acute surgical unit (ASU). Outcomes measured were time to operation, operating time, after-hours operation (6pm – 8am), length of stay and surgical complications.

Results

A total of 342 patients presented with acute biliary symptoms and were managed operatively. The median time to operation was significantly reduced in the ASU group (32.4 vs 25.4 hours, p=0.047), as were the proportion of operations performed after hours (19.5% vs 2.5%, p<0.001) and the median length of stay (4 vs 3 days, p<0.001). The median operating time, rate of conversion to open cholecystectomy and wound infection rates remained similar.

Conclusions

Implementation of an ASU can lead to objective differences in outcomes for patients who present with acute cholecystitis. In our study, the ASU significantly reduced time to operation, the number of operations performed after hours and length of stay.     

Influence of hydroxyurea on fetal hemoglobin production in vitro

Cytotoxic drugs increase circulating fetal hemoglobin levels. We examined the mechanism by measuring the fetal hemoglobin produced per BFU-E-derived erythroblast following hydroxyurea treatment in vivo and in vitro. Treatment of four sickle cell patients increased the percentage of circulating F reticulocytes. The frequencies of bone marrow or peripheral blood BFU-E or CFU-E-derived colonies and their fetal hemoglobin content were unaffected. In all cases, the number of erythroid cells/progenitor-derived colony increased. To explore further the effect of hydroxyurea on fetal hemoglobin production, we added 50 mumol/L hydroxyurea to cultures of peripheral blood BFU-E-derived erythroblasts on 1 of 9 days (day 5 through 13) to nine samples. These BFU-E were derived from the peripheral blood of normal donors, sickle trait donors, and sickle cell anemia patients and from the bone marrows of monkeys. This concentration of hydroxyurea was selected so that the frequency of BFU-E and their size was moderately decreased. Addition of hydroxyurea to these progenitor-derived erythroid cells had no effect on fetal hemoglobin content per cell. Neither did transient exposure of progenitors to hydroxyurea prior to culture in nontoxic concentrations (0 to 500 mumol/L) result in a significant increase in fetal hemoglobin content in progenitor-derived erythroblasts. These data suggest that hydroxyurea does not directly alter the HbF program expressed by progenitor-derived erythroid cells. Instead, it enhances hemoglobin F content secondarily, possibly by inducing alterations in erythropoiesis.     

Atrial fibrillation occurring early after cardiovascular surgery: impact of the surgical procedure

Purpose

Postoperative atrial fibrillation/flutter (AF) is still the most common complication after cardiovascular surgery, and it is important to determine the risk factors in order to establish effective management for recent postoperative AF. This study investigated the clinical predictors of postoperative AF using a prospectively collected database.

Methods

A total of 418 patients underwent cardiovascular surgery and were enrolled in this study. The relationship between postoperative AF and perioperative factors was examined.

Results

Postoperative AF occurred in 134 patients (32.1 %). A univariate analysis showed that an older age, hypertension, perioperative transfusion, use of cardiopulmonary bypass and thoracic aortic surgery were significantly associated with postoperative AF. The incidence of fibrillation was 49.4 % (39/79) in patients having aortic surgery. A multivariate analysis revealed that an older age, transfusion, and aortic surgery were all independent predictors of postoperative AF.

Conclusions

An older age, transfusion, and aortic surgery are strong independent predictors of postoperative AF. These findings help to identify high-risk patients for AF after cardiovascular surgery. Careful perioperative management is required for older patients undergoing aortic surgery with cardiopulmonary bypass.     

Kv7.2-7.5 voltage-gated potassium channel (KCNQ2-5) opener, retigabine, reduces capsaicin-induced visceral pain in mice

The taiep rat is a myelin mutant in which immobility episodes (IEs) can be induced in adult males by gripping. EEG recordings during gripping-induced IEs show a rapid eye movement (REM) sleep-like pattern, similar to that reported for narcolepsy-cataplexy suggesting that IEs represent a disorder of REM-sleep. An alpha(2) adrenoceptor agonist increases gripping-induced IEs, whereas alpha(2) antagonists decrease these. We have studied the effect of prazosin on IEs and the levels of alpha(1) adrenoceptors were evaluated in cerebro-cortical homogenates of taiep and control rats. Systemic administration of prazosin results in a significant increase in both the frequency and duration of gripping-induced IEs. Our results show that cerebro-cortical tissue is not an adequate candidate for the expression of cataplexy-like symptoms, but prazosin, an alpha(1) antagonist, is a potent inducer of gripping-induced immobility episodes in taiep rats.     

地高辛抗血清对老龄大鼠心肌缺氧复氧损伤影响的体外实验

目的:观察内洋地黄素水平在老龄大鼠心肌细胞缺氧复氧损伤中的变化以及地高辛抗血清的保护作用。方法:实验于2005-04/05在皖南医学院病理生理教研室完成。取10只24月龄和10只6月龄雄性普通级SD大鼠,分别制备青年和老龄大鼠心肌细胞匀浆,老龄和成年大鼠为两大组,每组分为7小组,即每只大鼠心肌随机分到各小组中,共计14小组,每组10支试管。正常对照组:给予CO2和O2的混合气体(1∶19)通气40min;缺氧复氧组:CO2,O2,N2混合气体(5∶4∶91)通气20min后换成CO2和O2的混合气体(1∶19)通气20min;阴性对照组:同缺氧复氧组,但于再给氧前加入0.1mL的非特异性灭活兔血清;地高辛抗血清组:同缺氧复氧组,但于再给氧前加入0.1mL的非特异性地高辛抗血清(分别为1∶90000,60000,30000,10000)。观察大鼠心肌细胞钠-钾-三磷酸腺苷酶活性和线粒体内钙聚集程度,分析其剂量-效应关系。结果:①缺氧复氧时,青年组和老龄组大鼠心肌分泌内洋地黄素均显著升高,但老龄组显著低于青年组[(0.081±0.03),(0.153±0.06);(0.074±0.04),(0.125±0.05)ng/g;P<0.05]。②缺氧复氧时,老龄组与青年组心肌细胞钠-钾-三磷酸腺苷酶活性显著受抑制[(0.239±0.015),(0.778±0.050);(0.350±0.047),(0.836±0.044)μkat/g;P<0.05],老龄组与青年组相比,其抑制效应显著增强(P<0.05)。③缺氧复氧时,老龄组线粒体内钙与青年组比较明显增强[(0.082±0.011),(0.495±0.095);(0.075±0.008),(0.412±0.084)mmol/L,P<0.05]。④老龄组和青年组相比,地高辛抗血清呈剂量依赖性的恢复钠-钾-三磷酸腺苷酶活性(r=0.695,0.797,n=5,P<0.05),减轻线粒体内钙聚集(r=-0.565,-0.649,n=5,P<0.05);经直线回归分析发现,老龄鼠回归系数大于青年组(酶活性抑制K=1.50,0.94,线粒体内钙K=-7.43,-6.46)。结论:心肌细胞缺氧复氧时,老龄鼠损伤较青年大鼠更显著,其机制与老龄大鼠心肌细胞钠-钾-三磷酸腺苷酶对内洋地黄素敏感性增加有关,地高辛抗血清对老龄大鼠心肌细胞缺氧复氧保护作用更有效。     

Contrasting effects of recombinant human granulocyte-macrophage colony- stimulating factor (CSF) and granulocyte CSF treatment on the cycling of blood elements in childhood-onset cyclic neutropenia

Recombinant human granulocyte colony-stimulating factor (G-CSF) treatment has been shown to increase average neutrophil counts substantially in patients with childhood-onset cyclic neutropenia (or "cyclic hematopoiesis"), but not to eliminate the cyclic oscillations of neutrophil counts or those of other blood elements (monocytes, platelets, eosinophils, and reticulocytes) that are characteristic of this hematopoietic disorder. Indeed, oscillations of neutrophil counts are amplified during G-CSF treatment. We have compared the effects of recombinant granulocyte-macrophage-CSF (GM-CSF) with those of G-CSF in three patients with this disease (2 men and 1 woman, 17, 30, and 32 years of age). These patients were treated with GM-CSF (2.1 micrograms/kg/day, subcutaneously) for 6 weeks, preceded and followed by 6 to 13 weeks of detailed observation to document changes in the cyclic oscillations of blood neutrophils and other blood elements; two of the patients were subsequently treated with G-CSF (5.0 micrograms/kg/d, subcutaneously) and observed for comparable periods of time. Unlike G-CSF treatment, which increased average neutrophil counts more than 20-fold, GM-CSF increased neutrophil counts only modestly, from 1.6- to 3.9-fold, although eosinophilia of varying prominence was induced in each patient. However, at the same time, GM-CSF treatment dampened or eliminated the multilineage oscillations of circulating blood elements (neutrophils, monocytes, platelets, and/or reticulocytes) in each of the patients. In contrast, G-CSF treatment of the same patients markedly amplified the oscillations of neutrophil counts and caused the cycling of other blood elements (monocytes in particular) to become more distinct. These findings support the conclusion that the distinctive cycling of blood cell production in childhood-onset cyclic neutropenia results from abnormalities in the coordinate regulation of both GM-CSF-responsive, multipotential progenitor cells and G-CSF-responsive, lineage-restricted, neutrophil progenitors.