Für die visuelle Wahrnehmung im Gehirn spielt die ungestörte Funktion von Neuronen und Gliazellen in der Netzhaut eine entscheidende Rolle. Viele schädigende Prozesse wie Entzündungen, Ischämien oder Traumata können zur Ödementstehung in der Netzhaut führen. Da die Netzhaut entwicklungsgeschichtlich einen vorverlagerten Teil des Zwischenhirns darstellt, lassen sich die pathophysiologischen Zusammenhänge, die zur Entstehung eines Netzhautödems führen, auch auf die Ödementstehung im Gehirn übertragen. Diese Arbeit beschäftigt sich mit dem Phänomen der Zellvolumenregulation von Müllerzellen – den hauptsächlich in der Netzhaut anzutreffenden Gliazellen – und leistet damit einen Beitrag zur Grundlagenerforschung der Ödementstehung in neuronalen Geweben. Die im Rahmen von Ödementstehungen regelmäßig zu beobachtenden Gefäßpermeabilitätserhöhungen führen in neuronalen Geweben auch zur Extravasation von Albumin. Unter diesem Gesichtspunkt untersucht die vorliegende Arbeit den Einfluss von bovinem Serumalbumin auf die Müllerzellen und die damit verbundenen Mechanismen am Modell der Netzhaut von Ratten.

The volume homeostasis of retinal glial cells is mediated by an autocrine purinergic mechanism of ion channel opening which is activated in response to a decrease in the extracellular osmolarity. Here, I show that erythropoietin (EPO) prevents the osmotic swelling of glial somata in retinal slices from control and diabetic rats, with a half-maximal effect at approximately 0.01 nM. The downstream signaling evoked by EPO includes a release of vascular endothelial growth factor from the cells which was blocked by Janus kinase and extracellular signal-regulated kinases (ERK)1/2 inhibitors. Transactivation of kinase insert domain-containing receptor/fms-like tyrosine kinase 1 (KDR/flk-1) evokes a calcium-dependent, exocytotic release of glutamate, followed by activation of group I/II metabotropic glutamate receptors which results in calcium-independent release of ATP and adenosine from the cells. The final step in this cascade is the activation of adenosine A(1) receptors which results in protein kinase A- and phosphoinositide 3-kinase-mediated opening of potassium and chloride channels. EPO receptor protein was immunohistochemically localized to the inner retina and photoreceptor inner segments. In isolated glial cells, EPO receptor protein is selectively localized to fibers which traverse the inner nuclear layer in situ. Inhibition of glial swelling might contribute to the neuroprotective action of EPO in the retina under pathological conditions.

Das extravaskuläre Lungenwasser (EVLW) bezeichnet eine Akkumulation extravaskulärer Flüssigkeit im Lungengewebe und ist charakteristisch für das akute Lungenversagen (ALI/ARDS). Die bettseitige Messung des EVLWs eröffnet dem Kliniker die Möglichkeit einer frühzeitigen Detektion und Quantifizierung eines Lungenödems. Neben gravimetrischen und bildgebenden Methoden ist das transpulmonale Thermodilutionsverfahren ein bettseitiges Verfahren zur EVLW Bestimmung. Das transpulmonale Thermodilutionsverfahren findet entweder als Doppel- oder als Einzelindikatorverfahren Anwendung. Das Einzelindikatorverfahren ist aufgrund der einfacheren und kosteneffektiveren Handhabung zu einer weitverbreiteten Methode geworden. Trotz guter Validierung an einer Vielzahl von alternativen Methoden zur EVLW Messung ist die Einzelindikatormethode nicht vollends etabliert. Daher bedarf es der Überprüfung der Zuverlässigkeit der EVLW Bestimmung durch das Einzelindikator-Thermodilutionsverfahren anhand anderer Methoden, die zur Quantifizierung von Lungenödemen eingesetzt werden können. Diese Arbeit ist Teil eines interdisziplinären Forschungsprojektes der veterinär- und humanmedizinischen Fakultäten der Universität Leipzig zur Quantifizierung eines durch Applikation des alpha2-Rezeptotagonisten Xylazin induzierten Lungenschadens im Großtiermodell der Spezies Schaf. Neben der quantitativen Computertomographie (qCT) wurde das Einzelindikator-Thermo¬dilutions¬verfahren zur Quantifizierung eines möglichen Lungenödems eingesetzt. Hierfür wurden 16 Versuchsschafe narkotisiert und maschinell beatmet. In zwei Experimenten wurde niedrig dosiertes Xylazin (0,15 mg/kg) und in einem dritten Experiment hoch dosiertes Xylazin (0,3 mg/kg) intravenös verabreicht. Alle drei Versuchsabschnitte wurden in denselben Tieren mit jeweils mindestens 8 Wochen Zeitabstand durchgeführt. Vor und wiederholt nach der Xylazinapplikation wurden mittels qCT das Gesamtlungengewicht (MLunge) und das Gesamtlungenvolumen (VLunge), sowie mittels Einzelindikatorverfahren das EVLW bestimmt. Für die Auswertung wurde auch der auf das Körpergewicht bezogene EVLW Index (EVLWI) verwendet. In allen drei Versuchsabschnitten stiegen nach Xylazinapplikation MLunge und EVLWI an, VLunge hingegen sank erheblich ab. Der EVLWI Anstieg erreichte nach Xylazingabe nicht die Schwellenwerte für das akute Lungenversagen, sondern war vereinbar mit einem gering bis mäßig ausgeprägten Lungenödem. Die CT-basierten Parameter bestätigten dies. Vielmehr konnte mit der qCT der Nachweis von Atelektasen als wesentliche Ursache der Belüftungsstörung nachgewiesen werden. Die EVLW Messung ermöglichte darüber hinaus die Differenzierung zwischen einem mäßigen und einem ausgeprägten Lungenödem. Die vorliegende Arbeit zeigte weiterhin, dass das EVLW mit dem simultan mittels qCT bestimmten Parameter MLunge korrelierte. Für die vorliegende Xylazin-induzierten Lungenveränderung wies das Einzelindikator-Thermodilutionsverfahren jedoch bei der Überwachung von Veränderungen des EVLWs, d.h. im Sinne eines Verlaufsparameters, Schwächen auf. Zusammenfassend war die Detektion des erhöhten EVLWs nach Xylazinapplikation durch die Einzelindikator-Thermodilutionsmethode zum Nachweis und zur Quantifizierung und Differenzierung der Xylazin-induzierten Belüftungsstörung übereinstimmend mit den Ergebnissen der qCT gut möglich. Für die quantitative und differentialdiagnostische Beurteilung von CT Infiltraten ist das mittels Einzelindikator-Thermodilutionsverfahren bestimmte EVLW damit ein hilfreicher, bettseitig bestimmbarer Parameter.

The transthoracic application of synchronized direct current cardioversion (DCC) is widely used to terminate atrial fibrillation, atrial flutter, and other supraventricular tachyarrhythmia. DCC is a highly effective method for acute restoration of sinus rhythm. Although DCC is a relatively safe and frequently performed procedure, data on potential side effects are very rarely reported in the literature. The most serious complications associated with DCC are thromboembolism and intracranial hemorrhage. The true incidence of postcardioversion pulmonary edema is not known, but it is estimated to occur in 1%to 3% of patients, particularly those with coexistent heart disease. We report on a patient with a structurally normal heart who developed acute pulmonary edema after undergoing DCC. The patient had no evidence of myocardial injury according to an electrocardiogram and cardiac biomarkers. The patient was treated with intravenous diuretics. After 4 days, the pulmonary edema resolved.

No description available.

The educational medium GetWellNetWork (GWNW) in a large magnet teaching facility offered few educational videos specific to vascular patients with a focus on leg elevation after lower extremity bypass surgery. Supplying patient-specific education has the potential for providing cost-effective nursing care to vascular patients and improving hospital reimbursement. Guided by the interactive care model, a storyboard was developed using best-practice evidence for vascular postoperative patients that could lead to the development of a video to address the educational needs of vascular patients upon discharge. The practice focused question asked if a video addressing the importance of leg elevation would improve patients’ use of in-house educational videos and stakeholder satisfaction. A vascular physician (n = 1) and nursing staff (n = 9) provided feedback on the appropriateness of the evidence-based educational content for the storyboard by completing a 9-item, open-ended survey. Survey results supported development of the video and revealed positive feedback on storyboard content and that staff with 1–3 years’ experience or 15+ years’ experience had an increased understanding of the importance of evidence-based guidelines for leg elevation for vascular patients. The feedback will be used to develop a vascular-patient-specific educational video. Encouraging patients to view the video on leg elevation has the potential to improve cost effectiveness of patient care and hospital reimbursement, prevent hospital readmission that could lead to patient and caregiver hardships associated with readmission, and improve the health outcomes for postoperative vascular patients.

BACKGROUND: Many different ocular diseases produce a common symptom of macular edema - a leakage of fluid into the retina. In addition to the presence of this structural aberration, functionally, the retina’s capacity to effectively conduct electrochemical signals will be impaired. The impediment can be demonstrated by a decreased electrical response measured via electroretinography (ERG) and visualized as a waveform with quantifiable amplitude. Macular edema and its associated effects on retinal structure and function are resultant of abnormal blood vessel growth, or angiogenesis. The process of angiogenesis involves a pathway of multiple growth factors and signaling molecules, including vascular endothelial growth factor (VEGF). Modern day treatments to help resolve macular edema target VEGF in order to inhibit pathological angiogenesis; two such anti-VEGF medications are aflibercept, or Eylea, and bevacizumab, also known as Avastin. This retrospective cohort study aims to compare the outcomes of patients treated with either Avastin or Eylea, and to observe what structural or functional changes occur in each sample. METHODS: This study included twelve eyes of 8 eligible patients that were injected with intravitreal Avastin for diabetic macular edema (DME), clinically significant macular edema (CSME), proliferative diabetic retinopathy, or non-proliferative diabetic retinopathy (NPDR), and had resolved macular edema. Five eyes of 6 eligible patients that were injected with intravitreal Eylea for NPDR, neovascular age-related macular degeneration (AMD), cystoid macular edema (CME), central retinal vein occlusion (CRVO), or DME, and had resolved edema were also included in the study. Patient data was randomly screened and collected via the MDIntelleSys (MDI) electronic medical record system at Fromer Eye Centers, New York. No personally identifiable information was collected in this study. The parameters used for comparison of the two anti-VEGF medications were the length of treatment, frequency of injection, change in ERG magnitude between subsequent scans, and net change in ERG magnitude between the baseline scan and the most recent scan obtained during the period of the study. The means of each parameter were determined to be the best measure of central tendency to summarize the data. Welch’s t-tests were conducted at a significance level of α= 0.05 between the parameters of each group to determine the significance of the differences in the means obtained. RESULTS: There was no significant difference found between the mean number of injections, time until recovery, change in magnitude, and net change in magnitude for both Avastin-treated patients and those treated with Eylea. CONCLUSION: The results of this study support the conclusion that both aflibercept and bevacizumab are comparably effective anti-VEGF treatments, in both relieving macular edema and restoring function in retinal cells. The similar outcomes observed in each treatment group offer insight into the versatility of anti-VEGF treatment and provide physicians with the flexibility of pursuing alternative medication options for their patients. Further study into the structural and functional effects of various anti-VEGF medications is needed to account for variables such as age, sex, race, or other possibly confounding factors. An inclusion of other quantifiable data such as visual acuity would also benefit this investigation. Furthermore, this study is limited by its focus solely on anti-VEGF medication; this subject of discussion would benefit from an experimental comparison between anti-VEGF treatments and other allopathic interventions. Recent studies have suggested alternatives to anti-VEGF altogether such as intravitreal triamcinolone acetonide and intravitreal steroids like dexamethasone, marketed as Ozurdex.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第12917号 / 論医博第2092号 / 新制||医||1009(附属図書館) / 32127 / 京都大学大学院医学研究科医学専攻 / (主査)教授 河野 憲二, 教授 大森 治紀, 教授 渡邉 大 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21629号 / 医博第4435号 / 新制||医||1033(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 伊佐 正, 教授 柳田 素子, 教授 宮本 享 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Ultrasound measurement of change in kidney volume is a sensitive indicator of severity of renal parenchymal injury. Am J Physiol Renal Physiol 319: F447–F457, 2020. First published July 20, 2020; doi:10.1152/ajprenal.00221.2020.—Noninvasive determination of the severity of parenchymal injury in acute kidney injury remains challenging. Edema is an early pathological process following injury, which may correlate with changes in kidney volume. The goal of the present study was to test the hypothesis that “increases in kidney volume measured in vivo using ultrasound correlate with the degree of renal parenchymal injury.” Ischemia-reperfusion (IR) of varying length was used to produce graded tissue injury. We first determined 1) whether regional kidney volume in rats varied with the severity (0, 15, 30, and 45 min) of warm bilateral IR and 2) whether this correlated with tubular injury score. We then determined whether these changes could be measured in vivo using three-dimensional ultrasound. Finally, we evaluated cumulative changes in kidney volume up to 14 days post-IR in rats to determine whether changes in renal volume were predictive of latent tubular injury following recovery of filtration. Experiments concluded that noninvasive ultrasound measurements of change in kidney volume over 2 wk are predictive of tubular injury following IR even in animals in which plasma creatinine was not elevated. We conclude that ultrasound measurements of volume are a sensitive, noninvasive marker of tissue injury in rats and that the use of three-dimensional ultrasound measurements may provide useful information regarding the timing, severity, and recovery from renal tissue injury in experimental studies.