Reply to Letter to the Editor: Pediatric Septic Arthritis and Osteomyelitis in the USA: A National KID Database Analysis

HSS Journal ® -     

Neuropeptide Y Attenuates Stress‐Induced Bone Loss Through Suppression of Noradrenaline Circuits

Chronic stress and depression have adverse consequences on many organ systems, including the skeleton, but the mechanisms underlying stress‐induced bone loss remain unclear. Here we demonstrate that neuropeptide Y (NPY), centrally and peripherally, plays a critical role in protecting against stress‐induced bone loss. Mice lacking the anxiolytic factor NPY exhibit more anxious behavior and elevated corticosterone levels. Additionally, following a 6‐week restraint, or cold‐stress protocol, Npy‐null mice exhibit three‐fold greater bone loss compared to wild‐type mice, owing to suppression of osteoblast activity. This stress‐protective NPY pathway acts specifically through Y2 receptors. Centrally, Y2 receptors suppress corticotropin‐releasing factor expression and inhibit activation of noradrenergic neurons in the paraventricular nucleus. In the periphery, they act to control noradrenaline release from sympathetic neurons. Specific deletion of arcuate Y2 receptors recapitulates the Npy‐null stress response, coincident with elevated serum noradrenaline. Importantly, specific reintroduction of NPY solely in noradrenergic neurons of otherwise Npy‐null mice blocks the increase in circulating noradrenaline and the stress‐induced bone loss. Thus, NPY protects against excessive stress‐induced bone loss, through Y2 receptor‐mediated modulation of central and peripheral noradrenergic neurons. © 2014 American Society for Bone and Mineral Research.     

DLA-identical bone marrow grafts after low-dose total body irradiation: the effect of canine recombinant hematopoietic growth factors

Previous studies found that bone marrow (BM) allografts from DLA- identical littermates resulted in survival of two thirds of recipient dogs after otherwise lethal doses of 450 to 600 cGy of total body irradiation (TBI) because of successful allografts or autologous recovery after rejection of the allografts. The current study asked whether survival could be further improved by treating allograft recipients with recombinant canine granulocyte colony-stimulating factor (G-CSF), stem cell factor (SCF), or G-CSF/SCF. Of 21 dogs, 14 (67%) receiving allografts but no growth factors survived, 10 with successful allografts (including 5 mixed chimeras) and 4 with autologous recovery; whereas 7 animals died, 5 from infections during BM aplasia and 2 from acute graft-versus-host disease. By comparison, 30 of 34 dogs (88%) receiving hematopoietic growth factors in addition to the BM graft survived, 17 with successful allografts (including 10 mixed chimeras) and 13 with autologous recovery; whereas 4 died, all with infection related to BM aplasia after rejection of the allograft. Survival was similar for recipients of G-CSF, SCF, or the combination of G-CSF and SCF. Logistic regression analyses, which accounted for possible effects of TBI dose, showed a trend for improved survival in dogs receiving growth factors (P = .09), no change in allogeneic engraftment (P = .74), and a slight increase in autologous recovery (P = .22). In agreement with previous data, we found that grafts of BM from DLA-identical littermates improved survival of recipient dogs exposed to low but otherwise lethal doses of TBI. A further improvement in survival could be achieved by additional treatment with G-CSF, SCF, or G-CSF/SCF. Results suggest that treatment by hematopoietic growth factors along with BM grafts should be considered for victims of radiation accidents.     

Publikationsleistungen der Universitätskliniken für Anästhesiologie

Aim

This study assessed the publication performance of university departments of anesthesiology in Austria, Germany and Switzerland. The number of publications, original articles, impact factors and citations were evaluated.

Material and methods

A search was performed in PubMed to identify publications related to anesthesiology from 2001 to 2010. All articles from anesthesiology journals listed in the fields of anesthesia/pain therapy, critical care and emergency medicine by the “journal citation report 2013” in Thomson Reuters ISI web of knowledge were included. Articles from non-anaesthesiology journals, where the stem of the word anesthesia (anes*, anaes*, anäst*, anast*) appears in the affiliation field of PubMed, were included as well. The time periods 2001–2005 and 2006–2010 were compared. Articles were allocated to university departments in Austria, Germany and Switzerland via the affiliation field.

Results

A total of 45 university departments in Austria, Germany and Switzerland and 125,979 publications from 2,863 journals (65 anesthesiology journals, 2,798 non-anesthesiology journals) were analyzed. Of the publications 23?% could not be allocated to a given university department of anesthesiology. In the observation period the university department of anesthesiology in Berlin achieved most publications (n?=?479) and impact points (1,384), whereas Vienna accumulated most original articles (n?=?156). Austria had the most publications per million inhabitants in 2006-2010 (n=50) followed by Switzerland (n=49) and Germany (n=35). The number of publications during the observation period decreased in Germany (0.5?%), Austria (7?%) and Switzerland (8?%). Tables 2 and 4–8 of this article are available at Springer Link under Supplemental.

Conclusions

The research performance varied among the university departments of anesthesiology in Germany, Austria and Switzerland whereby larger university departments, such as Berlin or Vienna published most. Publication output in Germany, Austria and Switzerland has decreased. Data processing in PubMed should be improved.     

Densitometric regional ejection fraction: a new three-dimensional index of regional left ventricular function--comparison with geometric methods

Densitometric regional ejection fraction obtained by computer analysis of digital subtraction ventriculography was evaluated as a new, quantitative, three-dimensional index of regional left ventricular performance. Eighteen patients with coronary artery disease and seven control subjects had right anterior oblique ventriculography at rest and immediately after rapid atrial pacing using central venous injection of contrast material. Regional left ventricular ejection fraction was determined by densitometry in six segments drawn around the end-diastolic center of gravity, and compared with two conventional indexes of segmental wall motion: area and radial regional ejection fraction. Densitometric, area or radial regional ejection fraction was classified as abnormal if it fell at least 2 standard deviations below the corresponding mean value in the normal group. The densitometric method did not require outlining of the end-systolic left ventricular silhouette and was the easiest and fastest to perform of all three techniques. In addition, intra- and interobserver reproducibilities were higher with the densitometric method (r = 0.97 and 0.95) than with either the area (r = 0.84 and 0.82) or the radial method (r = 0.82 and 0.76). Regional left ventricular dysfunction as assessed by the densitometric, area and radial techniques allowed the detection of coronary artery disease in 50, 50 and 44% of the patients at rest and in 83, 67 and 61% of the patients in the post-pacing period, respectively. Post-pacing regional left ventricular dysfunction accurately predicted the presence or absence of greater than 70% diameter stenosis in the supplying coronary artery in 75, 67 and 56% of the cases, respectively. Thus, densitometric analysis of digital subtraction ventriculography allows a fast and reproducible three-dimensional determination of regional left ventricular ejection fraction. Using this technique, pacing-induced regional dysfunction can be detected in most patients with coronary artery disease and corresponds well with the location of significant coronary artery lesions.     

Recurrent febrile panniculitis and hepatitis in two patients with acquired complement deficiency and paraproteinemia

Repeated episodes of febrile panniculitis and hepatitis were the main clinical features in two patients with an IgG1 kappa paraproteinemia and severe depletion of the early components of the classical pathway of complement (acquired C1 inhibitor deficiency). They did not have episodes of cutaneous angioedema or evidence of immune complex disease. In the more severely affected patient, the episodes responded to steroids. These features have not been described with acquired C1 inhibitor deficiency and may be related to complement activation.     

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.     

运动性心律失常

运动性心律失常是指发生于机体剧烈运动期间或之后的心律失常。临床表现不一,从心悸、头晕、晕厥、心绞痛、急性心肌梗死和充血性心力衰竭,甚至到心脏性猝死。运动性心律失常可见于心肌缺血,如患有动脉粥样硬化性心脏病以及患有原发性或继发性心肌病的患者。然而,也可能发生在似乎健康的个体。在后一组人群中,运动性心律失常可以是良性的,但也可以是获得性(如药物诱发)或先天性(如先天性长QT综合征或致心律失常性右室发育不良)心电活动或结构的异常而呈恶性。这种潜在病理生理学机制的复杂性,使运动性心律失常的诊断和治疗成为临床医学上的…     

The functional half-life of H-2Kd-restricted T cell epitopes on living cells

The functional half-life (t_1/2) of different complexes formed by major histocompatibility complex (MHC) class I molecules and antigen on the surface of target cells was measured using specific cytotoxic T lymphocyte (CTL) clones in cytolysis, and interferon-γ-production and Ca²⁺-mobilization assays. Functional t_1/2 values of 5–10 h were obtained, which are in accordance with some previous estimations obtained from biochemical and immunochemical measurements. Moreover, these values were independent of the type of target cell, fixation of the target cells, or proteases able to degrade the peptides, suggesting that the unfolding of the peptide/MHC complexes at the cell surface alone determines the functional t_1/2 of the CTL epitopes.