Die Azidose-induzierte Schwellung und intrazelluläre Azidose von Gliazellen - Bedeutung von Anionen und Kalzium

Die vorliegenden Untersuchungen stellen eine Fortsetzung langjähriger Versuche am Institut für Chirurgische Forschung dar, zellbiologische Mechanismen des zytotoxischen Hirnödems zu klären. Bislang konnten in einem in vitro Modell von Gliazellen verschiedene Mediatoren einer Gliazellschwellung im Sinne eines zytotoxischen Hirnödems charakterisiert werden. Darunter unter anderen eine Laktazidose – in Schweregraden wie sie bei Schädel-Hirn-Traumen und zerebralen Ischämien vorkommt. Ursächlich konnten sowohl der Na+/H+-Antiporter wie auch ein Chlorid- und Bikarbonat-abhängiges Transportsystem identifiziert werden die zur Akkumulation osmotisch aktiver Solute (Na+ und Cl-) in der Zelle führen und somit eine Zellschwellung bedingen. In der vorliegenden Arbeit sollten der Azidose-induzierten Schwellung zugrundeliegende Mechanismen, d.h. Membrantransporter und –kanäle weitergehend charakterisiert werden. Dabei wurde ein Schwerpunkt auf Anionentranporter und die Rolle von Kalziumionen gelegt. Die Untersuchungen erfolgten am Modell suspendierter C6 Gliomzellen als Modellzelle für Astrozyten. Durchflusszytometrisch wurde das Zellvolumen bestimmt ebenso der intrazelluläre pH unter Zuhilfenahme des pH-abhängigen Fluoreszenzfarbstoffes BCECF. Die Ergebnisse lassen sich folgendermaßen zusammenfassen: Setzt man C6 Gliomzellen einer Laktazidose von pH 6,2 aus, so kommt es zur prompten Zellschwellung die nach 60 min ihr Maximum bei 125,1 % des Ausgangsvolumens erreicht. Gleichzeitig kommt es zum Absinken des intrazellulären pH (pHi). Analoge Versuche in Chlorid- bzw. Bikarbonat-freiem Medium gingen mit einer deutlichen Hemmung der Azidose-induzierten Schwellung einher. Das Absinken von pHi war ebenfalls geringer ausgeprägt. Ähnliche Ergebnisse ließen sich mit den Inhibitoren des Cl-/HCO3--Antiporters DIDS und Niflumat erzielen. Die Zusammenschau dieser Ergebnisse lässt sie Schlussfolgerung zu, dass im Rahmen der Azidose-induzierten Schwellung der Na+-unabhängige Cl-/HCO3--Antiporter aktiv ist und zur Akkumulation von Chlorid in der Zelle führt und somit zur Zellschwellung beiträgt. Unter physiologischen Bedingungen hingegen ist der Na+-abhängige Cl-/HCO3--Antiporter aktiv und trägt zur Regulierung des ´steady state` pHi bei. In weiteren Versuchen konnte erstmals unter Verwendung der Na+-K+-Cl--Kotransportinhibitoren Bumetanid und Furosemid eine Beteiligung dieses Kotransporters an der Azidose-induzierten Schwellung nachgewiesen werden. Beide Inhibitoren führten zur deutlichen Reduktion der Zellschwellung ohne relevante Einflüsse auf den intrazellulären pH. Die Aktivierung des Transporters in Azidose führt zur Akkumulation der transportierten Ionen Natrium, Kalium und Chlorid in der Zelle, die dort als osmotisch wirksame Teilchen einen Wassereinstrom nach sich ziehen und auf diesem Wege zur Zellschwellung führen. Daneben wurde eine Abhängigkeit der Azidose-induzierten Schwellung von extrazellulären Kalziumionen gefunden. In Kalzium-freiem Medium ist ausschließlich die Zellschwellung deutlich reduziert während der Verlauf des intrazellulärem pH dem der Kontrollgruppe entsprach. Daraus lässt sich schlussfolgern, dass extrazelluläre Kalziumionen für die Aktivierung eines pH-unbeeinflussenden Transporters wie z.B. den Na+-K+-Cl--Kotransport notwendig sind. Die Chelierung intrazellulärer Kalziumionen hatte keinen Effekt auf die Azidose-induzierte Schwellung und den intrazellulären pH. Damit konnten die vorliegenden Untersuchungen die Bedeutung des Cl-/HCO3--Antiporters im Rahmen der Azidose-induzierten Schwellung näher charakterisieren und die Beteiligung des Na+-K+-Cl--Kotransportes erstmals nachweisen. Ebenfalls konnte die Bedeutung extra- nicht jedoch intrazellulärer Kalziumionen für die Azidose-induzierte Schwellung gezeigt werden

Risk factors for postoperative seizures in patients with chronic subdural haematomas

Postoperative seizures are a frequently occurring yet not well-understood complication in patients undergoing surgical treatment of chronic subdural haematomas (cSDHs). Therefore, we investigated surgical and non-surgical risk factors that are commonly considered causal in provoking epileptic seizures, paying special attention to the intracranial course of the subdural drain (SDD) and the configuration of the haematoma. Data of patients with a cSDH, that were treated at our neurosurgical department between 2008 and 2014 were analysed. Patients suffering from severe pre-existing conditions and those who have been treated conservatively were excluded. Epidemiologic data as well as relevant clinical data were collected. Pre- and postoperative CT scans were analysed regarding morpho- and volumetric parameters. In order to objectify the influence of the SDD, its intracranial course and localisation (entering angle as well as the angle between drain and brain surface) were measured. For statistical analysis, univariate and multiple logistic regression models as well as Fisher’s exact test were used. Two hundred eleven consecutive patients have been included. Mean age was 75.6 years, and 69% were male. Nineteen (9%) patients suffered from postsurgical seizures. Membranes within the haematoma were present in 81.5%. Pre- to postoperative haematoma reduction was significant (mean of difference − 12.76 mm/ − 9.47 mm in coronal/axial CT planes, p = 0.001/ < 0.001). In 77.9%, SDD showed cortical contact with eloquent regions and had an unfavourable course in 30 cases (14.2%). Surgical complications consisted of cortical bleeding in 2.5%, fresh subdural haematoma in 33.5% and wound infections in 1.4% of patients. Neither in univariate nor in multiple regression analyses any of the following independent variates was significantly correlated with postsurgical seizures: pre-existing epilepsy, alcohol abuse, right-sided haematomas, localization and thickness of haematoma, presence of septations, SDD-localization and to-brain angle, subdural air, and electrolyte levels. Instead, in multiple regression analyses, we found the risk of postsurgical seizures to be significantly correlated and increased with left-sided cSDH treated via craniotomy (p = 0.03) and an unfavourable course of the SDD in left-sided cSDH (p = 0.033). Burr hole trepanation should be preferred over craniotomy and care must be taken when placing a SDD to avoid irritating cortical tissue. The configuration of the haematoma does not appear to affect the postoperative seizure rate

Wohnen in Sachsen-Anhalt im demographischen Wandel: wie können Kommunen und Unternehmen auf Ansprüche einer älter werdenden Bewohnerschaft reagieren? ; Handlungsempfehlungen und Befunde aus der Forschung zum demographischen Wandel in Sachsen-Anhalt

Durch den fortschreitenden demographischen Wandel in Sachsen-Anhalt verändern sich zunehmend Wohnquartiere. Aus zwei an der MLU Halle-Wittenberg durchgeführten Forschungsprojekten des Instituts für Geographie wurde deutlich, dass sich einerseits Unternehmen auf altersspezifische Wünsche und Bedürfnisse einstellen müssen, andererseits werden Kommunen gezwungen sein, sich in Zukunft verstärkt mit einer älteren Klientel zu beschäftigen. Als Schnittpunkt werden beispielsweise generationengerechte Infrastruktur- und Dienstleistungsangebote gesehen. Bei einer alternsgerechten Ausrichtung von Kommunen können diese wirtschaftlich profitieren und so den eigentlichen Ortskern im suburbanen Raum wieder stärken. Der klassische suburbane Raum ist momentan kein attraktiver Wohnstandort für Senioren, kann aber z.B. durch Eigeninitiative von Wohneigentümern (Umbaumaßnahmen) und durch politische Entscheidungen (interkommunale Zusammenarbeit) aufgewertet werden. Dazu ist es aber auch notwendig, dass sowohl Unternehmen als auch Politik ältere Bürger stärker als bisher als eine wichtige Zielgruppe identifizieren und entsprechend handeln. (Autorenreferat)The advancing demographic change within Saxony-Anhalt leads to a shift in accommodation realities. Two research projects conducted by the Institute of Geography of the MartinLuther-University Halle-Wittenberg point out that companies need to adjust more to age-specific needs and that municipalities will be under further constraint to deal with an elderly clientele in the near future. A solution can be found by offering infrastructure and services being equally suitable for all generations. By aligning itself better to an aging population, the municipality could profit economically and therefore strengthen the town center of the suburban area, which at the moment is not desirable for elderly people to live in. Improvement may be realized through proactivity by proprietors (remodeling and rebuilding) as well as political decisions (intercommunal cooperation). It is therefore necessary that companies as well as politicians see elderly people as an increasingly important target group and act more appropriately than before. (author's abstract

Kontinuität und Wandel der Zielgebietspräferenzen und Motive älterer Binnenwanderer

Der Vergleich aktueller mit früheren Binnenwanderungsmustern älterer Menschen soll klären, inwieweit deren Zielgebiete und Migrationsmotive angesichts des Strukturwandels des Alters und zunehmender Übergänge von Babyboomern in den Ruhestand eher von Trendfortsetzungen oder -veränderungen geprägt sind. In der Zeitreihenbetrachtung haben sowohl die Standortverbundenheit der Zielgruppe als auch die Distanzempfindlichkeit überregionaler Ruhesitzwanderungen nach wie vor Bestand. Modifizierungen zeigen sich hingegen im Rahmen von interregionalen Verflechtungsanalysen: In Westdeutschland haben sich die ehemaligen Zielgebiete der älteren Fortzügler aus den Metropolen und Großstädten von den angrenzenden Umlandregionen zunehmend in periurbane und ländliche Räume verlagert. Demgegenüber verzeichnen ostdeutsche Städte Wanderungsgewinne, z. T. auch aus Rückwanderungen an den vertrauten Herkunftsort. Mit den wohnbedingten und netzwerkorientierten Motiven behalten die klassischen Umzugsdeterminanten ihren hohen Stellenwert. Im Vergleich zu früheren Untersuchungen weisen sie aktuell jedoch ein deutlich vielfältigeres Begründungsspektrum auf

How do spine surgeons cope with psychological distress : results of a cross-sectional study

Cross Sectional Study/Online Survey. In this study, we sought to assess stress, psychological distress, resilience, and coping strategies among spine surgeons in German-speaking countries. Recent studies have reported high rates of stress and burnout among surgeons. A survey via Survey Monkey™ was conducted among spine surgeons practicing in German-speaking countries using validated questionnaires for perceived stress, mental burden, resilience, and quality of life. Data on working situation and demographics were also collected. 582 surgeons responded to the survey, representing 15% of those surveyed. 79% of respondents were satisfied with their professional success. Mental burden was higher than in the general population, as was perceived stress. Chairpersons were exposed to the lowest levels of perceived stress and mental burden. Mental distress was high (GHQ ≥ 12) in 59% of residents and 27% chairpersons. Self-reported psychological resilience was higher than levels found in the general population and highest among chairpersons. Quality of life was comparable to levels reported in the general population. There were statistically significant correlations between perceived stress and mental burden scores (r s = 0.65, p < 0.001). Career level (senior physicians vs. residents, OR 0.26; 95% CI 0.10-0.66), perceived stress (OR 1.54; 95% CI 1.33-1.77), self-reported resilience (OR 0.53; 95% CI 0.33-0.84), and mental composite score (SOR 0.86; 95% CI 0.83-0.90) were predictors of high mental burden. There was no interaction between perceived stress and resilience on mental burden (p = 0.835). Spine surgeons are exposed to higher levels of stress than the general population, which are associated with higher mental distress. More professional experience and higher levels of psychological resilience are associated with lower levels of stress

Anxiety is associated with unfulfilled information needs and pain at the informed consent consultation of spine surgery patients : a longitudinal study

Purpose Meeting the information needs of patients adequately is of high importance in informed consent consultations in surgery. However, information needs often remain unmet in the informed consent consultation. The aim of this study was to assess anxiety and pain in relation to the patients’ information needs fulfillment perioperatively. Methods We applied a question prompt list (QPL) for patients undergoing spine surgery (SN-QPL) before (t1) and a question answering list (SN-QAL) after (t2) the informed consent consultation. The patients additionally completed the “State-Trait Anxiety Operation Inventory” (STOA, cognitive and affective scale) at t1, as well as a pain numerical rating scale (NRS) at t2 and postoperative (t3). We analyzed (1) the association between anxiety, information needs and pain and (2) anxiety and pain scores regarding information needs fulfillment after the consent consultation. Results A total of n = 118 patients was included. Affective and cognitive state anxiety was only reduced postoperatively (affective p < .001, cognitive p < .05). The higher trait anxiety was, the more patients longed for information at t1–t3 (t1: r = .58/r = .74, each p < .001), (t2: r = .38/r = .49, each p < .001) and (t3: r = .29, p < .01/r = 34, p < .001). Higher grades of trait anxiety resulted in lower information needs fulfilment. Higher state anxiety levels were associated with higher pain levels. Information needs more often remained unfulfilled in high trait and state anxiety patients. Conclusion Patients’ anxiety was associated with (un)fulfilled information needs. Meeting information needs should be optimized in the process of surgeon–patient communication. Adapting the information to the patients’ anxiety levels seem to be an effective way to reduce anxiety

Großwohnsiedlungen als Ankunftsquartier? Wanderungsbewegungen und Segregationsprozess in Halle (Saale)

In Germany, large residential housing estates built during the 1950s to 1980s have become important areas for migrants and refugees. In Eastern Germany, estates from the socialist era have lost many of their inhabitants following the reunification in 1990. Some, like those in the city of Halle (Saale), have lost more than half of their population. This downward trend has stopped now and in some areas, population size grows. For Halle (Saale), we computed the in and out-migration of large socialist housing estates from 2011 to 2018 and compared it to the late 19th century parts of the inner city which are now well-sought after residential areas. We find that German residents have left in great numbersthe estates. At the same time, migrants have moved in even greater numbers to the estates. Most of them did not come from the parts of the inner city, suggesting that displacement through gentrification has not (yet) been the decisive factor for ethnic segregation. However, some migrant households are now, most recently, moving away from the estates as well and towards the city centre. This suggests that ethnic segregation is now being superseded by social segregation.In der MLU Human Geography Working Paper Series werden in unregelmäßigen Abständen aktuelle humangeographische Forschungsergebnisse des Instituts für Geowissenschaften & Geographie der Martin-Luther-Universität Halle-Wittenberg in deutscher und englischer Sprache veröffentlicht

Comparison of unruptured intracranial aneurysm treatment score and PHASES score in subarachnoid hemorrhage patients with multiple intracranial aneurysms

Objective: Unruptured Intracranial Aneurysm (UIA) Treatment Score (UIATS) and PHASES score are used to inform treatment decision making for UIAs (treatment or observation). We assessed the ability of the scoring systems to discriminate between ruptured aneurysms and UIAs in a subarachnoid hemorrhage (SAH) cohort with multiple aneurysms.Methods: We retrospectively applied PHASES and UIATS scoring to the aneurysms of 40 consecutive patients with SAH and multiple intracranial aneurysms.Results: PHASES score discriminated better between ruptured aneurysms and UIAs than UIATS. PHASES scores and the difference between the UIATS subscores were higher for ruptured aneurysms compared with UIAs, which reached significance for the PHASES score. PHASES score estimated a low 5-year rupture risk in a larger proportion of the UIAs (≤0.7% in 62.3%, ≤1.7% in 98.4%) than of the ruptured aneurysms (≤0.7% in 22.5%, ≤1.7% in 82.5%). In the 40 ruptured aneurysms, UIATS provided recommendation for treatment in 11 (27.5%), conservative management in 14 (35.0%), and was inconclusive in 15 cases (37.5%). In the 61 UIAs, UIATS recommended treatment in 16 (26.2%), conservative management in 29 (47.5%), and was inconclusive in 16 (26.2%) cases.Conclusion: Similar to previous SAH cohorts, a significant proportion of the ruptured aneurysms exhibited a low-rupture risk. Nevertheless, PHASES score discriminated between ruptured aneurysms and UIAs in our cohort; the lower discriminatory power of UIATS was due to high weights of aneurysm-independent factors. We recommend careful integration of the scores for individual decision making. Large-scale prospective trials are required to establish score-based treatment strategies for UIAs

Distress and quality of life do not change over time in patients with operated and conservatively managed intracranial meningioma

Purpose The patients’ burden with asymptomatic meningiomas and patients with good clinical outcome after meningioma resection often remains neglected. In this study, we aimed to investigate the longitudinal changes of psychological distress and quality of life in these patient groups. Methods Patients with conservatively managed (CM) or operated (OM) meningiomas and excellent neurological status, who were screened for psychological distress during the follow-up visit (t1), were included. We performed a follow-up mail/telephone-based survey 3–6 months (t2) after t1. Distress was measured using Hospital Anxiety and Depression Scale (HADS), Distress Thermometer (DT), 36-item Short Form (SF-36), and Brief Fatigue Inventory (BFI). Results Sixty-two patients participated in t1 and 47 in t2. The number of patients reporting increased or borderline values remained high 3 months after initial presentation, with n = 25 (53%) of patients reporting increased anxiety symptom severity and n = 29 (62%) reporting increased depressive symptom severity values. The proportion of distressed patients according to a DT score remained similar after 3 months. Forty-four percent of patients reported significant distress in OM and 33% in CM group. The most common problems among distressed patients were fatigue (t2 75%) and worries (t2 50%), followed by pain, sleep disturbances, sadness, and nervousness. Tumor progress was associated with increased depression scores (OR 6.3 (1.1–36.7)). Conclusion The level of psychological distress in asymptomatic meningiomas and postoperative meningiomas with excellent outcome is high. Further investigations are needed to identify and counsel the patients at risk

An age-dependent outcome analysis of microvascular decompression and percutaneous thermocoagulation in trigeminal neuralgia

BACKGROUND Trigeminal neuralgia (TN) is a severe pain condition and the most common facial neuralgia. While microvascular decompression (MVD) presents an excellent treatment in neurovascular compression cases, percutaneous thermocoagulation (PT) of the ganglion Gasseri is an alternative option. This study aimed to evaluate post-operative complication rate and outcome of both treatment strategies related to the patient’s age. METHODS The medical records of all patients with the diagnosis of trigeminal neuralgia undergoing an MVD or PT of the ganglion Gasseri (between January 2007 and September 2017) were reviewed to determine the efficacy and the complication rate of both methods in regard to the patient’s age. RESULTS Seventy-nine patients underwent MVD surgery and 39 a PT. The mean age of patients in the MVD group was 61 years and 73 years in the PT group. There were 59 (50%) female patients. Nerve-vessel conflict could be identified in 78 (98.7%) MVD and 17 (43.6%) PT patients on preoperative MRI. Charlson comorbidity index was significantly higher in PT group (2.4 (1.8) versus 3.8 (1.8) p < 0.001). The Barrow pain score (BPS) at the last follow-up demonstrated higher scores after PT (p = 0.007). The complication rate was markedly higher in PT group, mostly due to the facial hypesthesia (84.6% versus 27.8%; p < 0.001). Mean symptom-free survival was significantly shorter in the PT group (9 vs. 26 months, p < 0.001). It remained statistically significant when stratified into age groups: (65 years and older: 9 vs. 18 months, p = 0.001). Duration of symptoms (OR 1.005, 95% CI 1.000–1.010), primary procedure (OR 6.198, 95% CI 2.650–14.496), patient age (OR 1.033, 95% CI 1.002–1.066), and postoperative complication rate (OR 2.777, 95% CI 1.309–5.890) were associated with treatment failure. CONCLUSION In this patient series, the MVD is confirmed to be an excellent treatment option independent of patient’s age. However, while PT is an effective procedure, time to pain recurrence is shorter, and the favorable outcome (BPS 1 and 2) rate is lower compared to MVD. Hence MVD should be the preferred treatment and PT should remain an alternative in very selected cases when latter is not possible but not in the elderly patient per se