1,721,003 research outputs found
TNF-alpha inhibition using etanercept prevents noise-induced hearing loss by improvement of cochlear blood flow in vivo
No full textObjective: Exposure to loud noise can impair cochlear microcirculation and cause noise-induced hearing loss (NIHL). TNF-alpha signaling has been shown to be activated in NIHL and to control spiral modiolar artery vasoconstriction that regulates cochlear microcirculation. It was the aim of this experimental study to analyse the effects of the TNF-alpha inhibitor etanercept on cochlear microcirculation and hearing threshold shift in NIHL in vivo. Design: After assessment of normacusis using ABR, loud noise (106 dB SPL, 30 minutes) was applied on both ears in guinea pigs. Etanercept was administered systemically after loud noise exposure while control animals received a saline solution. In vivo fluorescence microscopy of strial capillaries was performed after surgical exposure of the cochlea for microcirculatory analysis. ABR measurements were derived from the contralateral ear. Study sample: Guinea pigs (n=6, per group). Results: Compared to controls, cochlear blood flow in strial capillary segments was significantly increased in etanercept-treated animals. Additionally, hearing threshold was preserved in animals receiving the TNF-alpha inhibitor in contrast to a significant threshold raising in controls. Conclusions: TNF-alpha inhibition using etanercept improves cochlear microcirculation and protects hearing levels after loud noise exposure and appears as a promising treatment strategy for human NIHL
Acute hyperfibrinogenemia impairs cochlear blood flow and hearing function in guinea pigs in vivo
No full textObjective: Impairment of microcirculation is a possible cause of sudden sensorineural hearing loss (SSNHL). Fibrinogen is known as a risk factor for both microvascular dysfunction and SSNHL. Therefore, the aim of this study was to investigate the effect of elevated serum levels of fibrinogen on cochlear blood flow and hearing function in vivo. Design: One group of guinea pigs received two consecutive injections of 100 mg fibrinogen while a control group received equimolar doses of albumin. Measurements of cochlear microcirculation by intravital microscopy and of hearing thresholds by auditory brainstem response (ABR) recordings were carried out before, after first and after second injection. Study sample: Ten healthy guinea pigs were randomly assigned to a treatment group or a control group of five animals each. Results: Serum fibrinogen levels were elevated after the first and second injections of fibrinogen compared to basal values and control group respectively. Increasing levels of fibrinogen were paralleled by decreasing cochlear blood flow as well as increasing hearing thresholds. Hearing threshold correlated negatively with cochlear blood flow. Conclusions: The effect of microcirculatory impairment on hearing function could be explained by a malfunction of the cochlear amplifier. Further investigation is needed to quantify cochlear potentials under elevated serum fibrinogen levels
Etanercept Prevents Decrease of Cochlear Blood Flow Dose-Dependently Caused by Tumor Necrosis Factor Alpha
No full textObjectives: Tumor necrosis factor alpha (TNF-alpha) is a mediator of inflammation and microcirculation in the cochlea. This study aimed to quantify the effect of a local increase of TNF-alpha and study the effect of its interaction with etanercept on cochlear microcirculation. Methods: Cochlear lateral wall vessels were exposed surgically and assessed by intravital microscopy in guinea pigs in vivo. First, 24 animals were randomly distributed into 4 groups of 6 each. Exposed vessels were superfused repeatedly either with 1 of 3 different concentrations of TNF-alpha (5.0, 0.5, and 0.05 ng/mL) or with placebo (0.9% saline solution). Second, 12 animals were randomly distributed into 2 groups of 6 each. Vessels were pretreated with etanercept (1.0 mu g/mL) or placebo (0.9% saline solution), and then treated by repeated superfusion with TNF-alpha (5.0 ng/mL). Results: TNF-alpha was shown to be effective in decreasing cochlear blood flow at a dose of 5.0 ng/mL (p < 0.01, analysis of variance on ranks). Lower concentrations or placebo treatment did not lead to significant changes. After pretreatment with etanercept, TNF-alpha at a dose of 5.0 ng/mL no longer led to a change in cochlear blood flow. Conclusions: The decreasing effect that TNF-alpha has on cochlear blood flow is dose-dependent. Etanercept abrogates this effect
Head and neck solitary fibrous tumors: a rare and challenging entity
No full textThe objective of this study is to analyze the outcome of treatment for solitary fibrous tumors (SFTs) in the head and neck area. SFTs present as slow-growing masses, often with local compressive symptoms that are difficult to distinguish from other soft-tissue tumors. SFTs are commonly treated using local excision without adjuvant therapy. To date, only heterogeneous small series have been published, documenting the treatment results and outcome with these tumors. Retrospective study of patients with histopathologically confirmed SFT treated at two tertiary referral hospitals between 2004 and 2014. Eight men and four women with histologically confirmed SFT were identified in the records. Their age range was 37-82 years (mean 57.8 years). The mean follow-up period for eight patients was 6.75 years (range 1-24 years). Four patients were lost to follow-up. Sublocalizations were neck (n = 3), orbit (n = 2), paranasal sinus (n = 2), cheek (n = 2), hard palate (n = 1), parotid gland (n = 1), and tongue (n = 1). The first-line treatment for all of the tumors identified was surgical excision. In four cases, the surgical margins were narrow or unclear due to piecemeal resection in the paranasal sinus and orbit (n = 3) or a tumor location deep in the parapharyngeal space (n = 1). Recurrences developed in two of these cases (in the orbit and parapharyngeal space), and the other two patients were lost to follow-up. Radiotherapy and chemotherapy were not administered as first-line treatments. Overall, the local recurrence rate (n = 2/8) was 25 %. The disease-specific survival rate was 100 %. These results are consistent with the literature data and show that safe surgical excision, without opening of the tumor capsule, reduces the risk of local recurrence and leads to a favorable outcome. Tumors in the head and neck often represent a surgical challenge, and wide surgical margins are rarely possible due to the complex three-dimensional anatomic compartments in the region. Head and neck surgeons should therefore be aware that there is an increased risk of recurrence in these patients; tightly scheduled follow-up visits are mandatory for at least 10 years, if not longer. Radiotherapy only appears to be an option in patients with unresectable tumors or when wide surgical excision would cause severe functional morbidity
Etanercept Prevents Decrease of Cochlear Blood Flow Dose-Dependently Caused by Tumor Necrosis Factor Alpha
No full textObjectives: Tumor necrosis factor alpha (TNF-alpha) is a mediator of inflammation and microcirculation in the cochlea. This study aimed to quantify the effect of a local increase of TNF-alpha and study the effect of its interaction with etanercept on cochlear microcirculation. Methods: Cochlear lateral wall vessels were exposed surgically and assessed by intravital microscopy in guinea pigs in vivo. First, 24 animals were randomly distributed into 4 groups of 6 each. Exposed vessels were superfused repeatedly either with 1 of 3 different concentrations of TNF-alpha (5.0, 0.5, and 0.05 ng/mL) or with placebo (0.9% saline solution). Second, 12 animals were randomly distributed into 2 groups of 6 each. Vessels were pretreated with etanercept (1.0 mu g/mL) or placebo (0.9% saline solution), and then treated by repeated superfusion with TNF-alpha (5.0 ng/mL). Results: TNF-alpha was shown to be effective in decreasing cochlear blood flow at a dose of 5.0 ng/mL (p < 0.01, analysis of variance on ranks). Lower concentrations or placebo treatment did not lead to significant changes. After pretreatment with etanercept, TNF-alpha at a dose of 5.0 ng/mL no longer led to a change in cochlear blood flow. Conclusions: The decreasing effect that TNF-alpha has on cochlear blood flow is dose-dependent. Etanercept abrogates this effect
Betahistine exerts a dose-dependent effect on cochlear stria vascularis blood flow in guinea pigs in vivo.
Full text linkBetahistine is a histamine H(1)-receptor agonist and H(3)-receptor antagonist that is administered to treat Menière's disease. Despite widespread use, its pharmacological mode of action has not been entirely elucidated. This study investigated the effect of betahistine on guinea pigs at dosages corresponding to clinically used doses for cochlear microcirculation. Thirty healthy Dunkin-Hartley guinea pigs were randomly assigned to five groups to receive betahistine dihydrochloride in a dose of 1,000 mg/kg b. w. (milligram per kilogram body weight), 0.100 mg/kg b. w., 0.010 mg/kg b. w., 0.001 mg/kg b. w. in NaCl 0.9% or NaCl 0.9% alone as placebo. Cochlear blood flow and mean arterial pressure were continuously monitored by intravital fluorescence microscopy and invasive blood pressure measurements 3 minutes before and 15 minutes after administration of betahistine. When betahistine was administered in a dose of 1.000 mg/kg b. w. cochlear blood flow was increased to a peak value of 1.340 arbitrary units (SD: 0.246; range: 0.933-1.546 arb. units) compared to baseline (p<0.05; Two Way Repeated Measures ANOVA/Bonferroni t-test). The lowest dosage of 0.001 mg/kg b. w. betahistine or NaCl 0.9% had the same effect as placebo. Nonlinear regression revealed that there was a sigmoid correlation between increase in blood flow and dosages. Betahistine has a dose-dependent effect on the increase of blood flow in cochlear capillaries. The effects of the dosage range of betahistine on cochlear microcirculation corresponded well to clinically used single dosages to treat Menière's disease. Our data suggest that the improved effects of higher doses of betahistine in the treatment of Menière's disease might be due to a corresponding increase of cochlear blood flow
Modeling the Measurements of Cochlear Microcirculation and Hearing Function after Loud Noise
Full text linkObjective: Recent findings support the crucial role of microcirculatory disturbance and ischemia for hearing impairment especially after noise-induced hearing loss (NIHL). The aim of this study was to establish an animal model for in vivo analysis of cochlear microcirculation and hearing function after a loud noise to allow precise measurements of both parameters in vivo.
Study Design: Randomized controlled trial.
Setting: Animal study.
Subjects and Methods: After assessment of normacusis (0 minutes) using evoked auditory brainstem responses (ABRs), noise (106-dB sound pressure level [SPL]) was applied to both ears in 6 guinea pigs for 30 minutes while unexposed animals served as controls. In vivo fluorescence microscopy of the stria vascularis capillaries was performed after surgical exposure of 1 cochlea. ABR measurements were derived from the contralateral ear.
Results: After noise exposure, red blood cell velocity was reduced significantly by 24.3% (120 minutes) and further decreased to 44.5% at the end of the observation (210 minutes) in contrast to stable control measurements. Vessel diameters were not affected in both groups. A gradual decrease of segmental blood flow became significant (38.1%) after 150 minutes compared with controls. Hearing thresholds shifted significantly from 20.0 ± 5.5 dB SPL (0 minutes) to 32.5 ± 4.2dB SPL (60 minutes) only in animals exposed to loud noise.
Conclusion: With regard to novel treatments targeting the stria vascularis in NIHL, this standardized model allows us to analyze in detail cochlear microcirculation and hearing function in vivo
Geschlechtsspezifischer Unterschied von Varizenblutungen und Nicht-Varizenblutungen bei Leberzirrhose auf die Sterblichkeit
Full text linkDie Erkrankung der Leberzirrhose ist nach wie vor für beide Geschlechter mit einer schlechten Prognose verknüpft. Das klinische Bild einer OGIB (VB und NVB) sind signifikante Diagnosen und Signale, die geschlechtsspezifisch den Therapieverlauf bestimmen sollten.
Zusammenfassend lässt sich sagen, dass die PatientInnen-Prognose nicht nur vom Typ der Blutungsursache abhängt, sondern auch vom Geschlecht; es mag nötig sein, verschiedene Bewältigungsstrategien auf Basis dieser beiden Faktoren zu ergreifen.
Die vorliegende Studie zeigt, dass die Komplikation der VB im Vergleich zu NVB eine höhere Sterblichkeit bei Männern verursachen, während bei den Frauen der GIB-Typus keinen Einfluss auf das Ergebnis hat. Dies unterstreicht, dass geschlechtsspezifisches klinisches Management auf dem Blutungstypus nach der Endoskopie basieren sollte
Untersuchung der Bedeutung einer postoperativen verlängerten invasiven Beatmung bei geriatrischen Patienten mit intrakraniellem Meningeom
Full text linkMeningeome sind gutartige intrakranielle Tumore. Sie haben ihren Ursprung nicht im Gehirnparenchym selbst, sondern gehen von den Meningealzellen der weichen Hirnhäute aus (Alruvaili und De Jesus, 2021). Häufig im Rahmen einer Zufallsbefundung entdeckt, neigen Meningeome (je nach ihrer Größe und/oder Lokalisation) jedoch auch zur Ausbildung neurologischer Symptome (Alruvaili und De Jesus, 2021). Aufgrund ihrer Benignität ist in der Vielzahl der Fälle von einem langsamen Wachstum auszugehen. Eine zufallsbefundliche, kleine, nicht raumfordernde Meningeom-suspekte Raumforderung kann jedoch durchaus Kriterien der Resektionswürdigkeit erfüllen, wie z. B. bei jüngeren Patienten mit entsprechender Lebenserwartung.
Allgemeinhin darf im Falle eines Meningeoms ohne neurologische Symptomatik also von einer elektiven Indikationsstellung gesprochen werden. Elektiven Operationen schwingt häufig eine beruhigende Planbarkeit mit, dennoch sind diese durchaus mit einem gewissen Risiko eines ungünstigen Ergebnisses verbunden (Reponen et al., 2014). Im Falle eines fortgeschrittenen Lebensalters kann auch eine elektive Operation eine deutliche Belastung darstellen (Johans et al., 2017). So ist ein wichtiger Punkt in der präoperativen Patientenberatung, ob und in wieweit ältere (geriatrische) Patienten das Risiko einer (elektiven) operativen Therapie auf sich nehmen sollten, im Vergleich zum erwartenden Ausgang.
Mit steigendem Alter wächst das Unbehagen der Betroffenen vor intensivmedizinischen Behandlungen, welche unter Umständen von medizinischen Laien als Gerätemedizin kritisch angesehen wird (Valentin, 2017). Insbesondere nach intrakraniellen Eingriffen (wie beim Meningeom), aber auch bei entsprechendem perioperativen Risiko (wie bei geriatrischen Patienten) ist eine postoperative intensivmedizinische Behandlung oftmals notwendig (Badenes et al., 2017). Aus diesem Grund konzentrierten wir uns in der vorliegenden Dissertationsschrift auf die für ein schlechtes Outcome vulnerabelste Patientengruppe mit operativ zu entfernendem Meningeom, nämlich die der
geriatrischen.
Hinsichtlich der postoperativen Morbidität und Mortalität von geriatrischen Patienten nach Meningeom-Resektion wurden in der Vergangenheit viele Versuche unternommen, die präoperative Risikoabschätzung zu verbessern (Cohen-Inbar et al., 2010; Cohen-Inbar et al., 2011; Cohen-Inbar, 2019). Um der zuvor genannten „Gerätemedizin“ gerecht zu werden, wurde in der vorliegenden Arbeit eine prolongierte invasive Beatmungsnotwendigkeit als Surrogatparameter benutzt.
Die Inzidenz und Folgen einer sogenannten postoperativen prolonged mechanical ventilation (PMV) wurde bereits bezüglich anderer Ätiologien (z. B. in der Kardiologie oder Herzchirurgie) untersucht und hierbei der Zusammenhang von PMV und einer hohen Sterblichkeitsrate nachgewiesen (Papathanasiou et al., 2019; Suarez-Pierre et al., 2019). Für neurochirurgische Erkrankungen ist der Einfluss der PMV jedoch kaum untersucht (Schuss et al., 2020).
Somit war es das Ziel der vorliegenden Dissertationsschrift, zunächst die Klärung der Wahrscheinlichkeit des Auftretens einer PMV bei geriatrischen Patienten mit geplanter Meningeom-Resektion zu untersuchen. Anschließend war es Zielsetzung dieser Arbeit, aus der gefundenen Auftretenswahrscheinlichkeit des PMV nunmehr auch eine klinische Implikation dessen für dieses neurochirurgische Patientenkollektiv abzuleiten. Hierfür wurde der Zusammenhang von postoperativer PMV mit der Mortalität von geriatrischen Patienten nach elektiver Meningeom-Resektion untersucht. Kann durch diesen Zusammenhang mit der Mortalität eine klinische Relevanz für den Parameter PMV abgeleitet werden, so sollen Risikofaktoren für ein solches PMV in dieser speziellen Patientenkohorte identifiziert werden. Anschließend sollen diese Risikofaktoren in einem klinisch relevanten Risiko-Score zusammengefasst werden, um somit die Ergebnisse dieser Arbeit einfach und übersichtlich für die präoperative Beratung von geriatrischen Patienten mit geplanter Resektion eines intrakraniellen Meningeoms zur Verfügung stellen zu können.ACKT: A Proposal for a Novel Score to Predict Prolonged Mechanical Ventilation after Surgical Treatment of Meningioma in Geriatric Patients
Indication for surgical treatment in patients with intracranial meningioma must include both clinical aspects and an individual risk-benefit stratification, especially in geriatric patients. Prolonged mechanical ventilation (PMV) has not been investigated for its potential effects in patients with meningioma. We therefore analyzed the impact of PMV on mortality in geriatric patients who had undergone meningioma resection. Between 2009 and 2019, 261 patients aged ≥ 70 years were surgically treated for intracranial meningioma at our institution. PMV was defined as postoperative invasive ventilation of > 7 days. Postoperative PMV was present in 17 of 261 geriatric meningioma patients (7%). Twenty-five geriatric patients (10%) died within 1 year after surgery. A scoring system ("ACKT") based on the variables of age, preoperative C-reactive protein (CRP) value, Karnofsky performance scale and tumor size supports prediction of postoperative PMV (sensitivity 73%, specificity 84%). PMV is significantly associated with increased mortality after surgical treatment of meningiomas in geriatric patients. Furthermore, we suggest a novel score ("ACKT") to preoperatively estimate the risk of PMV occurrence, which might help to guide future risk-benefit assessment and patient counseling in the geriatric meningioma population
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