Angle Correction in Transcranial Doppler Sonography

Since the introduction of transcranial Doppler sonography in the early 1980s, flow velocity estimates have assumed a 0- to 30-degree angle of insonation. Based on limited radiological and anatomical studies. such an assumption appeared justified, and seemed to confer only minimal potential for error due to the cosine function in the Doppler formula. The introduction of transcranial color duplex sonography allows the direct evaluation of this assumption and the effect on flow velocities. Fifteen healthy volunteers were studied bilaterally using a unilateral transtemporal approach from the right. Velocity measurements were taken from the middle, anterior, and posterior cerebral arteries. Flow velocities were obtained with and without angle correction (0 degree). After completion of the color duplex study, velocities were obtained with a conventional, “blind” Doppler transducer at corresponding depths. For all insonated vessels the average angle of insonation was around 30 degrees. However, there was a wide variability of individual angles of insonation (0–70 degrees) in specific vessels. In 74.5% of all vessels, the angle-corrected flow velocity did not exceed the uncorrected velocity by more than 25%. In 14.5% the angle-corrected velocity was 25 to 50% higher and in 10.8% it was more than 50% higher as compared to the uncorrected velocity. Thus, the angle of insonation was unpredictable and often higher than originally expected. Angle-corrected velocities were higher than uncorrected values, and were more than 25% higher in about one-fourth of the vessels studied. Understanding of the clinical importance of such differences requires further study.     

短暂性全面遗忘症患者颈静脉瓣关闭不全的发病率升高

目的:短暂性全面遗忘症(TG A)的临床定义很明确,但关于其病因学尚不清楚。脑内静脉高压和继发的海马及间脑结构损伤是其可能的病因。在Valsalva手法检查期间对患者的颈静脉逆流进行直接研究,以确定颈静脉瓣关闭不全对TGA患者的脑内静脉高压是否有促进作用。方法:采用多普勒超声     

Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE

Increased concentrations of DNA-containing immune complexes in the serum are associated with systemic autoimmune diseases such as lupus. Stimulation of Toll-like receptor 9 (TLR9) by DNA is important in the activation of plasmacytoid dendritic cells and B cells. Here we show that HMGB1, a nuclear DNA-binding protein released from necrotic cells, was an essential component of DNA-containing immune complexes that stimulated cytokine production through a TLR9-MyD88 pathway involving the multivalent receptor RAGE. Moreover, binding of HMGB1 to class A CpG oligodeoxynucleotides considerably augmented cytokine production by means of TLR9 and RAGE. Our data demonstrate a mechanism by which HMGB1 and RAGE activate plasmacytoid dendritic cells and B cells in response to DNA and contribute to autoimmune pathogenesis.     

Validity and reliability of an ultrasound device for detecting carotid emboli.

Cardioembolic mechanisms cause 15 to 20% of all strokes and may account for the high incidence of neurological dysfunction associated with cardiopulmonary bypass. Accurate identification of high-risk subjects and/or surgical techniques would allow more effective testing and implementation of preventive or therapeutic measures to help reduce morbidity and mortality. This article reports on validity and reliability testing of a new emboli detection device that allows continuous monitoring of the common carotid artery. The instrument appears to be capable of detecting accurately particles of 193 mu or less in diameter and is highly reliable both within and between observers. In preliminary clinical use, the instrument also detected embolic signals in all patients monitored during cardiopulmonary bypass, while none were detected in healthy control subjects. These results establish the validity and reliability of a new emboli detection device and suggest its potential application to emboli detection monitoring during cardiopulmonary bypass.     

Palliative care in a general teaching hospital. 2. Establishment of a service.

OBJECTIVE: To assess the first year of operation of a palliative care service in a general teaching hospital. DESIGN, SETTING, PATIENTS: A retrospective analysis of 241 terminally ill patients referred to the Austin Hospital Palliative Care Service during its first year of operation. MAIN OUTCOME MEASURES: The occurrence and relief of pain, the occurrence and management of social and psychological problems, involvement of allied health services and the place of death. MAIN RESULTS: Unrelieved pain was the most frequent medical problem but, with appropriate medical management as well as input from other members of the multidisciplinary team, all patients achieved satisfactory pain control. The occurrence and severity of social and psychological problems was greater than expected. Most of the patients were discharged home and referred to domiciliary palliative care services; one-quarter of patients were able to die at home, one-third died in an inpatient hospice, and the remainder died in hospital. CONCLUSIONS: The Service was able to achieve most of its stated aims and has generated a much improved appreciation of the palliative care needs of patients with terminal illness and their families within the Hospital. A multidisciplinary approach to the management of terminally ill patients is crucial, and this Service has been successful despite limited staffing because of the willing involvement of other Units and Services in the Hospital. The difficulties inherent in the evaluation of a palliative care program (quality of life, cost-effectiveness) are discussed.     

Chromosomenuntersuchungen an menschlichen Fibroblastenkulturen nach Zugabe von Cyproheptadin

Cyproheptadin was tested on chromosomes in fibroblast cultures of children for its possible mutagenic efficacy. Neither 24-hour exposure to Cyproheptadin at concentrations of 8–16 mg/l medium nor a chronic exposure for 8–11 weeks at a concentration of 8 mg/l caused any discernable chromosomal mutations. At concentrations between 8–16 mg/l reversible cytomorphological and cytochemical changes occured; 32 mg/l suppressed cell division and higher concentrations (64–128 mg/l) brought about irreversible changes leading to cell death. These reactions were rather in vitro cytotoxic effects of unspecific nature.     

Nucleic acid-sensing TLRs and autoimmunity: novel insights from structural and cell biology

Invasion of pathogenic microorganisms or tissue damage activates innate immune signaling receptors that sample subcellular locations for foreign molecular structures, altered host molecules, or signs of compartment breaches. Upon engagement of innate immune receptors an acute but transient inflammatory response is initiated, aimed at the clearance of pathogens and cellular debris. Among the molecules that are sensed are nucleic acids, which activate several members of the transmembrane Toll-like receptor (TLR) family. Inappropriate recognition of nucleic acids by TLRs can cause inflammatory pathologies and autoimmunity. Here, we review the mechanisms involved in triggering nucleic acid-sensing TLRs and indicate checkpoints that restrict their activation to endolysosomal compartments. These mechanisms are crucial to sample the content of endosomes for nucleic acids in the context of infection or tissue damage, yet prevent accidental activation by host nucleic acids under physiological conditions. Decoding the molecular mechanisms that regulate nucleic acid recognition by TLRs is central to understand pathologies linked to unrestricted nucleic acid sensing and to develop novel therapeutic strategies.     

HMGB1 signals through toll-like receptor (TLR) 4 and TLR2

In response to bacterial endotoxin (e.g., LPS) or endogenous proinflammatory cytokines (e.g., TNF and IL-1beta), innate immune cells release HMGB1, a late cytokine mediator of lethal endotoxemia and sepsis. The delayed kinetics of HMGB1 release makes it an attractive therapeutic target with a wider window of opportunity for the treatment of lethal systemic inflammation. However, the receptor(s) responsible for HMGB1-mediated production of proinflammatory cytokines has not been well characterized. Here we demonstrate that in human whole blood, neutralizing antibodies against Toll-like receptor 4 (TLR4, but not TLR2 or receptor for advanced glycation end product) dose-dependently attenuate HMGB1-induced IL-8 release. Similarly, in primary human macrophages, HMGB1-induced TNF release is dose-dependently inhibited by anti-TLR4 antibodies. In primary macrophages from knockout mice, HMGB1 activates significantly less TNF release in cells obtained from MyD88 and TLR4 knockout mice as compared with cells from TLR2 knockout and wild-type controls. However, in human embryonic kidney 293 cells transfected with TLR2 or TLR4, HMGB1 effectively induces IL-8 release only from TLR2 overexpressing cells. Consistently, anti-TLR2 antibodies dose-dependently attenuate HMGB1-induced IL-8 release in human embryonic kidney/TLR2-expressing cells and markedly reduce HMGB1 cell surface binding on murine macrophage-like RAW 264.7 cells. Taken together, our data suggest that there is a differential usage of TLR2 and TLR4 in HMGB1 signaling in primary cells and in established cell lines, adding complexity to studies of HMGB1 signaling which was not previously expected.     

Schlaganfall

Zusammenfassung Der Schlaganfall ist mittlerweile eine behandelbare Erkrankung geworden. Pharmakologische Ansätze wie die Thrombolyse mit rt-PA, aber auch fundiertere Kenntnisse zu den erforderlichen Basismaßnahmen eröffnen insbesondere bei der Ischämie neue therapeutische Möglichkeiten. Aber das Zeitfenster ist eng, Transport in die Klinik und erste diagnostische Maßnahmen sollten spätestens 3 h nach Beginn der Symptomatik abgeschlossen sein: time is brain! Doch nach wie vor geht zu viel Zeit verloren durch eine zu späte Verständigung des Rettungsdienstes oder durch unzureichende Logistik im Krankenhaus. Stroke Units sind in allen Bundesländern etabliert und haben sich auf die Behandlung des akuten Schlaganfall spezialisiert. Eine enge lokale und regionale Kooperation von Rettungsdiensten und Krankenhäusern sowie eine gute Aufklärungsarbeit der Bevölkerung sind erforderlich, um im Ernstfall einen reibungslosen und schnellen Ablauf zu gewährleisten.