X-chromosomal gebundener Hydrozephalus (HSAS) Eine Erkrankung aus der Gruppe der CRASH-Syndrome

Hintergrund.  

Unter CRASH-Syndrom wird eine Gruppe von X-chromosomal vererbten Erkrankungen zusammengefasst, die eine Mutation im L1CAM-Gen vorweisen und nach dem Akronym CRASH folgende Symptome vorweisen k?nnen: Corpus-callosum-Hypoplasie, Retardierung, adduzierte Daumen, spastische Paraplegie und Hydrozephalus. Eine Erkrankung aus dieser Reihe ist der X-chromosomal gebundene Hydrozephalus, erstmals beschrieben von Bickers und Adams 1949 als Hydrozephalus mit ?quaduktstenose (HSAS).     

Kontraktur,Zuckung und Calcium

Zusammenfassung Es wurden Überlegungen und Experimente darüber angestellt, ob und wie das Ca bei der Kontraktur und bei der Zuckung von Skeletmuskeln beteiligt ist. Vor allem interessierte die Frage, ob es verschieden gebundenes bzw. lokalisiertes Ca in der Muskelfaser gibt, das unterschiedlich in Funktion treten kann (Kontraktur- bzw. Zuckungs-Ca). Im einzelnen konnten folgende Befunde erhoben werden:1. Wird ein Ganzmuskel (Sartorius) in Ca-freie Ringer-Lösung gebracht, so sinkt das Membranpotential seiner Fasern an der Oberfläche (und wahrscheinlich auch in der Tiefe) relativ langsam und wenig ab.Man kann daraus schließen, daß offenbar noch sehr lange etwas Ca von innen nach außen wandert, das ausreicht, einen großen Teil der Fasern vor stärkerer Depolarisation zu schützen. Trotzdem verliert der Muskel seine Kontrakturfähigkeit. Dies bedeutet, daß während der Ca-Verarmung eines Ganzmuskels die zur Kontrakturunfähigkeit führende Insuffizienz der elektromechanischen Kopplung schon einsetzt, bevor die Muskelfasern im Durchschnitt stärker depolarisiert und deswegen unerregbar geworden sind. Inwieweit diese am Ganzmuskel erhobenen Befunde auch für die isolierte Einzelfaser gelten, muß noch offenbleiben. Diesbezügliche eigene und fremde Untersuchungsergebnisse werden diskutiert.2. Es wird gezeigt, daß das die Kontraktur ermöglichende Ca leicht gebunden und leicht beweglich ist (Kontraktur-Ca). Dies trifft besonders für den Calciummechanismus tonischer Fasern zu. Sie können z.B. leicht Ca aus dem umgebenden Medium aufnehmen und dadurch ihre Kontrakturfähigkeit steigern. Auch Zuckungsfasern können aus einer Careichen Lösung viel Ca aufnehmen, doch wird ihre Kontrakturfähigkeit dadurch im Vergleich zu den tonischen Fasern viel weniger gesteigert. Das Ca wird hier offenbar in der Zelle rasch und so gebunden, daß es selbst durch den Trigger der depolarisierenden Kontraktursubstanz (z. B. KCl) nicht ausreichend mobilisiert werden kann.3. Dieses (im sarkoplasmatischen Reticulum?) fester gebundene Ca wird bei der Ca-Verarmung (Ca-freies Außenmedium) nur schwer und langsam abgegeben. Es scheint für die Zuckung gebraucht zu werden. Denn Zuckungen sind noch möglich, wenn im Verlauf der Ca-Verarmung keine Kontrakturen (und Nachkontrakturen) mehr auslösbar sind, d. h. das locker gebundene Ca der Zelle stark reduziert ist.4. Der Grund für die rasche Ermüdbarkeit Ca-verarmter Muskeln bei wiederholter elektrischer Reizung (Einzelzuckungen und Tetani) liegt weniger in einer Insuffizienz der mechanischen Ankopplung als in einer fortschreitenden Depolarisation der Muskelfasern infolge verlangsamter bzw. ungenügender Repolarisation.5. Es wird folgende Arbeitshypothese aufgestellt:Die Auslösung der Zuckung und der Kontraktur folgt einem verschiedenen Zeitfaktor. Nur der schnelle Trigger des Aktionspotentials vermag das im Zellinnern fester gebundene Ca für die Zuckung freizusetzen, das in einer Folgereaktion rasch wieder gebunden wird. Dagegen mobilisiert die langsame Depolarisation durch Kontrakturstoffe gerade das locker gebundene Ca, das beim Vorhandensein geeigneter Wege bzw. Transportmechanismen (worüber vorzugsweise die tonischen Muskelfasern verfügen) ins Faserinnere diffundieren und die Fibrillen nacheinander aktivieren kann.6. Die kontrakturauslösende Wirkung von H⁺- und Phosphat^–––-Ionen auch bei Ca-verarmten Muskeln beruht wahrscheinlich auf ihrer Fähigkeit, fest gebundenes Ca freizusetzen.

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Summary Questions were raised and experiments were done to see if and how Calcium is associated with twitches and contractures of skeletal muscles. The main question that interested us was are there different bound or localized Ca fractions in a muscle fibre, which perform different functions (contracture- or twitch-calcium)? The following facts were shown:1. If a whole muscle (sartorius muscle) was brought into a calciumfree Ringer's solution, then the membrane potential on its surface (and probably in the depth of the fibres also) would sink comparatively slowly and comparatively little.From this fact one can say that apparently for a long time sufficient Ca diffuses from the inside to the outside fibres of the muscle to protect these fibres form a stronger depolarization. Even though the muscle looses its ability to make contractures. This means that the insufficiency of the electromechanical-coupling mechanism (causing the inability for contractures) starts during the Ca-deprivation of a whole muscle before a stronger depolarization and inexcitability of the fibres can be observed on the average. How much one can compare this reaction on the whole muscle with a reaction on a single muscle fibre is still unanswered. Our own experimental results and other experimental results are discussed.2. It is shown that the Ca-fraction that is responsible for contractures is only lightly bound and very lightly mobile (contracture-Ca). This applies especially to the calcium mechanism of tonic muscles. These muscles can, for example, absorb calcium very easily from the surrounding medium and through this they can increase their contracture ability.The twitch fibres can also take up much calcium from a calcium-rich surrounding, but their contracture ability is much less than those of the tonic type. Apparently the Ca is bound fast and in such a way by the cell that even if the cell is depolarized by a contracture substance (for example KCl), it doesn't respond well because the calcium can't be mobilized fast enough.3. This more solidly bound Ca (in the sarcoplasmatic reticulum?) is given off only slowly and with much resistance to the outside by calcium loss (surroundings are free of calcium). This calcium seems to be used for the twitches, because twitsche are still possible during the time of Ca-loss when one can't cause any contractures (or after-contractures), that is, when the loosly bound calcium is reduced.4. The reason that a calcium-deficient muscle gets fatigued so fast after continued electrical irritation (single twitches and tetanus) is not to be found so much in an insufficiency of the mechanical coupling as in an continuing depolarization of the muscle fibres following a slowed up or insufficient repolarization.5. The following working hypothesis is suggested:The causing mechanisms of the twitch and contracture are governed by different time factors. Only the fast trigger of the action potential has the ability to set free the stronger bound calcium in the interior of the cell, which in a following reaction would be very quickly bound again. On the other side, slow depolarization with contracture substances mobilizes just that loosly bound calcium, which in the presence of suitable ways of transportation mechanisms (whereby we have merely here the tonic muscles) diffuses into the centre of the fibre and can activate the fibriles one after another.6. That H⁺- and PO ₄ ^––– -ions, also in calcium deficient muscles can cause contractures is probably based upon the ability of the muscles to set free strongly bound calcium.

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Mit 8 Textabbildungen

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Mit Unterstützung der Deutschen Forschungsgemeinschaft.     

Atypical chronic lymphocytic inflammation with pontocerebellar perivascular enhancement responsive to steroids (CLIPPERS), primary angiitis of the CNS mimicking CLIPPERS or overlap syndrome? A case report

A novel type of encephalomyelitis was first described as chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) in 2010 and few additional patients were reported since then. Partially due to its unknown aetiology and a lack of pathognomonic features some have suggested that CLIPPERS may not represent a distinct disease, but rather a syndrome with different underlying aetiologies. Here we report a 49-year-old German female who presented with a number of clinical and paraclinical features described as typical for CLIPPERS, while additionally showing symptoms and findings compatible with primary angiitis of the CNS (PACNS). This case may establish a previously unnoted link between two poorly understood autoimmune conditions of the CNS.     

Immediate Release 3D-Printed Tablets Produced Via Fused Deposition Modeling of a Thermo-Sensitive Drug

Purpose

Dissolution speeds of tablets printed via Fused Deposition Modeling (FDM) so far are significantly lower compared to powder or granule pressed immediate release tablets. The aim of this work was to print an actual immediate release tablet by choosing suitable polymers and printing designs, also taking into account lower processing temperatures (below 100°C) owing to the used model drug pantoprazole sodium.

Methods

Five different pharmaceutical grade polymers polyvinylpyrrolidone (PVP K12), polyethylene glycol 6000 (PEG 6000), Kollidon® VA64, polyethylene glycol 20,000 (PEG 20,000) and poloxamer 407 were successfully hot-melt-extruded to drug loaded filaments and printed to tablets at the required low temperatures.

Results

Tablets with the polymers PEG 6000 and PVP K12 and with a proportion of 10% pantoprazole sodium (w/w) demonstrated a fast drug release that was completed within 29 min or 10 min, respectively. By reducing the infill rate of PVP tablets to 50% and thereby increase the tablet porosity it was even possible to reduce the mean time for total drug release to only 3 min.

Conclusions

The knowledge acquired through this work might be very beneficial for future FDM applications in the field of immediate release tablets especially with respect to thermo-sensitive drugs.

     

Perceptions and acceptability of piloted Taenia solium control and elimination interventions in two endemic communities in eastern Zambia

Infections with Taenia solium cause significant public health and economic losses worldwide. Despite effective control tools, long‐term sustained control/elimination of the parasite has not been demonstrated to date. Success of intervention programs is dependent on their acceptability to local communities. Focus group discussions (FGDs) and questionnaires (QS) were conducted in two study communities in eastern Zambia to assess local perceptions and acceptance of two piloted intervention strategies: one targeting pigs only (‘control’ study arm), and one integrated human‐ and pig‐based (‘elimination’) strategy. QS (n = 227) captured data regarding participation in project activities, knowledge and perceptions of T. solium and of the interventional drugs used in the study. FGDs (n = 18) discussed perceived advantages and disadvantages of the interventions and of the project's delivery and value. QS data revealed 67% of respondents participated in at least one educational activity, and 80% correctly identified at least one disease targeted by the education. All elimination study arm respondents (n = 113) had taken the human treatment, and 98% intended to do so next time. Most (70%) indicated willingness to pay for future treatments (median 0.20 USD per dose). Of pig‐owning respondents, 11/12 (92%) had allowed their pigs to be treated/vaccinated and all intended to do so again next time. Four pig owners indicated willingness to pay 0.10–0.50 USD per dose of treatment or vaccine. FGD feedback revealed positive perceptions of interventions; people reported improved health in themselves and their pigs, and fewer cysticerci in pork. Latrine use, hand washing, meat inspection and proper cooking of pork had reportedly increased since the program's inception. Preliminary assessment indicates that the piloted intervention methods are generally acceptable to the communities. The reported willingness of many respondents to pay for the medications would contribute to the feasibility of long‐term, government‐led T. solium intervention programs in future.     

Constructing and identifying predictors of frailty among homeless adults—A latent variable structural equations model approach

Homeless urbanites are a heterogeneous population with unique health and social service needs. The study examined situational, behavioral, health-related and resource indicators in terms of their direct impact on frailty, hypothesized as a latent variable. Using structural equation modeling (SEM), a model was tested with 150 homeless men and women, ages 40–73, from three homeless day center drop-in sites on Skid Row and one residential drug treatment (RDT) facility that works with homeless parolees and probationers. In bivariate analyses with the latent construct frailty, months homeless (p < 0.01), female gender (p < 0.05), education (p < 0.05), comorbid conditions (p < 0.001), nutrition (p < 0.001), resilience (p < 0.001), health care utilization (p < 0.01), and falls (p < 0.001) were significantly associated with frailty. In the final path model, significant predictors of frailty included educational attainment (p < 0.01), comorbid conditions (p < 0.001), nutrition (p < 0.001), resilience (p < 0.001), and falls (p < 0.01). These findings will serve as a foundation for future nurse-led, community-based initiatives that focus on key predictors of frailty among the homeless and the development of interventions.