Das Kurzdarmsyndrom in Deutschland

Objective

As data about prevalence and standard of care in short bowel syndrome (SBS) are not available for Germany, this study estimated the prevalence and assessed the medical infrastructure to potentially improve care of SBS patients.

Methods

In a validated approach for prevalence estimation in rare diseases, a randomized census of 478 size-stratified hospitals with surgical, internal medicine and pediatric departments was conducted to estimate SBS prevalence. The number of SBS patients, specialized outpatient clinics and caregiver expertise were assessed.

Results

The response rate was 85?% of randomized hospitals (405/478). Strata-derived estimation yielded a total of 2,808 SBS patients in Germany for 2011/2012 (95?% CI: 1750.3865), translating into a prevalence estimation for 34/million inhabitants (95?% CI: 21.47). Overall expertise in SBS treatment was only rated “satisfactory” by most caregivers. While 86 specialized outpatient clinics were identified, there was no central registry to access these resources.

Conclusion

Short bowel syndrome, with a newly estimated prevalence of 34/million inhabitants is not a very rare medical condition in Germany. The interdisciplinary approach needed for optimal care for SBS patients would be greatly facilitated by a central registry.     

Evaluation of safety and efficacy as an adjuvant for the chitosan-based vaccine delivery vehicle ViscoGel in a single-blind randomised Phase I/IIa clinical trial

ViscoGel, a chitosan-based hydrogel, has earlier been shown to improve humoral and cell-mediated immune responses in mice. In this study, a Phase I/IIa clinical trial was conducted to primarily evaluate safety and secondarily to study the effects of ViscoGel in combination with a model vaccine, Act-HIB to Haemophilus influenzae type b, administered as a single intramuscular injection. Healthy volunteers of both sexes, ages 22–50 and not previously vaccinated to HIB, were recruited. The trial had two phases. In Phase A, three ascending dose levels of ViscoGel (25, 50 and 75 mg) were evaluated for safety in 3 × 10 subjects. Phase B had a single-blind, randomised, parallel-group design evaluating safety and efficacy in five groups, 20 subjects/group, comparing vaccination with 0.2 μg or 2 μg Act-HIB alone or combined with ViscoGel (50 mg) and one group receiving the standard Act-HIB dose (10 μg). No safety or tolerability concerns were identified. Local, transient reactions at the injection site were the most common adverse events. These were more frequent in groups receiving Act-HIB + ViscoGel, while other AEs were recorded at similar frequency in Act-HIB and Act-HIB + ViscoGel groups. Efficacy was evaluated by measuring serum anti-HIB antibodies and cellular responses in peripheral blood mononuclear cells (PBMC). There was a large variation in baseline anti-HIB antibody titres and no adjuvant effect was observed on the anti-HIB antibody production in groups vaccinated with Act-HIB + ViscoGel. ELISpot analyses revealed increased interferon-γ (IFN-γ) responses to Act-HIB in PBMCs from subjects vaccinated with Act-HIB in combination with ViscoGel, compared to groups receiving Act-HIB alone. Moreover, ViscoGel counteracted an inhibitory effect of Act-HIB vaccination on the IFN-γ response to both the vaccine itself and an irrelevant influenza antigen. In summary, ViscoGel was found to be safe and well-tolerated, supporting further examination of ViscoGel as a new innovative vehicle for vaccine development.     

Experimentelle Studien über die Sekundärknötchen in den Kniekehlenlymphknoten des Kaninchens bei Bacillus pyocyaneus-Infektion

Zusammenfassung Die Frage ist, ob eine Neubildung von Sekundärknötchen in den Kniekehlenlkn des Kaninchens nach Einspritzung einer virulenten Bacillus pyocyaneuskultur in dem abhängigen Lymphgefäßgebiet eintritt oder nicht. Eine genaue Methode für die Bestimmung der Mengen der verschiedenen Gewebsbestandteile der Lkn wurde ausgearbeitet (s. S. 260), und mit dieser Methode wurden Lkn von 11 normalen und 22 Versuchstieren untersucht.Bei dem Vergleich der Mengenwerte der Lkn der eingespritzten Seite mit denen der nicht gespritzten, sowie jener mit den Werten völlig normaler Tiere ergab sich in sämtlichen Versuchen in den Lkn der gespritzten Seite eine bedeutende Neubildung von Skn. Diese Neubildung war von 5 bis zu 7 Tagen nach der Einspritzung zu verspüren. Nach etwa 10–20 Tagen erreichte sie ihren Höhepunkt, und die betreffenden Lkn übertrafen die der anderen Seite sowie die der normalen Tieren um Hunderte von Skn. Nach einem Monat waren die Skn wieder in Rückbildung begriffen. Dieses Verhalten scheint uns eine gewisse Stütze zu sein für dieHellmansche Auffassung, daß die Skn Reaktionszentren gegen Spaltpilze usw. darstellen.Die bekannte Schwellungsreaktion des lymphatischen Gewebes auf Antigene verschiedener Art kam auch in unseren Versuchen deutlich zum Ausdruck. Durch Gewichitsbestimmungen der Popliteallkn von 49 normalen Tieren zeigte es sich, daß der Gewichtsunterschied unter normalen Verhältnissen im allgemeinen höchstens 1 cg beträgt. Ganz anders verhielten sich die Versuchstiere. In den ersten Versuchstagen war der Lkn der gespritzten Seite immer sehr stark geschwollen und übertraf den der anderen Seite um viele cg. Diese Gewichtsvermehrung nahm während des Verlaufs der Versuche ununterbrochen ab. Die betreffende Schwellungsreaktion fällt nicht mit der Sknneubildungsreaktion zusmmmen, denn die Schwellung ist schon im Abklingen begriffen, wenn die Neubildung von Skn ihren Höhepunkt — nach etwa 10–20 Tagen — erreicht.Die durchschnittliche Größe der Skn war in den Lkn der gespritzten Seite im allgemeinen verhältnismäßig groß. Jedoch ließ sich in dieser Beziehung keine regelmäßige Reaktion nachweisen. Auch über die Rinden- und Markprozentzahlen läßt sich nichts sicheres aussagen.Wir haben unsere Schnittreihen auch einer genauen mikroskopischen Musterung unterworfen. Diese hat vor allem gezeigt, daß keine nachweisbare allgemeine Reaktion des lymphatischen Systems bei den Einspritzungsversuchen vorhanden war. Die Reaktion schien vielmehr an den Lkn der gespritzten Seite streng lokalisiert zu sein. Nur hier ließen sich entzündliche Veränderungen verschiedener Art nachweisen.Mit 15 Abbildungen im Text     

躯干运动和负重时对足底支撑面侧向横移的姿势控制

目的:本研究假设自主运动命令和姿势控制信号间有冲突,因此设计在附加重物和不同自主任务的同时给予足底一个模拟受滑的干扰(横移)来观察姿势变化并分析其是否受冲突命令或者力学参数的影响.方法:受试者在执行各种不同的自主任务时,随机给予足底支撑面一个左侧或右侧的横移干扰.这些不同的自主任务包括不负重静止站立、静止站立单手负重5kg、负重5kg站立并躯干静止侧屈15°、负重5kg动态地提重物和放重物5项任务.测量和分析下列参数:中心压力的侧位移(COP)、躯干和股部在冠状面上的角位移和腹内压(IAP).结果:干扰离开质量(向右)、始反应超射的幅度、达到终平衡的时间和达到平衡前COP位移的次数都增加,这种情况可以看作是为了再获得平衡的姿势反应效率降低,因此,如果质量的重力效果能对抗干扰,则再获得平衡的反应效率甚至可以被增进.结论:提重和负重是危害姿势反应效率的因素,因为提重和负重改变了重力效果,加大了对躯干的干扰.在动态条件下躯干的运动不是被横移干扰增强就是被横移干扰抵消,并没有显著地影响改变最终平衡位置姿势校正的效应.因此附加任务的同时给一个支持面上的横移干扰,姿势控制的效应可以被抵消.这个减低的效应可以引起脊柱周围结构的负荷增加和增加受伤的危险性.但是,在恰当地放置负重的位置时,反而可以增进躯干控制和协助恢复姿势平衡.     

A pH-sensitive microsphere system for the colon delivery of tacrolimus containing nanoparticles.

Nanoparticles (NP) are known to accumulate at the site of inflammation in inflammatory bowel disease. In order to avoid premature uptake or degradation of NP during their passage through the small intestine, it appeared necessary to devise a form of local delivery system for NP. Tacrolimus (FK506) loaded poly(lactic-co-glycolic acid) NP entrapped into pH-sensitive microspheres (NPMS) were designed to achieve greater selectivity to their site of action when administered orally. The therapeutic efficacy of this drug delivery system was tested in an experimental colitis in rats. The in vitro characterization showed a successful incorporation of FK506-NP and strongly pH-sensitive release kinetics of both NP and drug. During the in vivo studies, clinical activity, colon/body weight index, and myeloperoxidase activity were determined to assess the severity of inflammation. Systemic availability of a fluorescent dye entrapped in the microspheres was measured in order to determine possible adverse effects. The NPMS as well as the controls of NP and MS formulations exhibited significant mitigating effects in the clinical activity index after 3 days of treatment with similar levels for the various therapies. When observing colon/body weight index and myeloperoxidase activity, only the NPMS group reached statistically significant differences (P<0.05) compared to the colitis control group while other groups did not (colitis control: 21.94+/-4.97; FK506 solution: 15.81+/-3.42; FK506-NP: 17.03+/-5.52; FK506-MS: 15.17+/-7.81; and FK-NPMS: 10.26+/-7.76 U/mg tissue). Moreover, the NPMS system reduced the systemic absorption of the entrapped dye compared to the dye solution or simple NP formulation (relative biovailability-solution: 100+/-14.9%; NP: 46.8+/-8.6%; and NPMS: 29.4+/-3.3%). The results suggest that the NPMS system can provide selective delivery of NP in the colon and develop a significant mitigating effect, while the control group treatments appeared to be insufficient.     

October 2001: 40-year-old Xhosa male with back pain and leg weakness

A 40-year-old Xhosa male presented with progressive upper lumbar back pain and weakness At examination he was emaciated and had enlarged lymph nodes in the groin and axilla. Both lower limbs were severely atrophic and weak. Sensation to touch and pain was decreased below L3 bilaterally. MR of the spine showed a discrete, contrast-enhancing epidural mass. A T10-T12 laminectomy revealed an soft, vascular extradural tumor dorsal to the cord. The mass was loosely applied to the dura and easy to remove. The operative specimen consisted of a sausage-shaped (3.5 x 2.0 x 1.2 cm), thinly-encapsulated mass of reddish-brown tissue. The cut surface had a mottled, vaguely nodular, yellowish-brown appearance. Microscopic examination revealed sheets of hematopoeitic elements, including myeloid, red cell and megakaryocytic lines, the latter showing Factor 8-related positivity. The final diagnosis was extramedullary hematopoiesis (EMH). A bone marrow biopsy performed as a result of the diagnosis showed a myeloproliferative disease and polycythemia vera. EMH in the spinal epidural space is a rare but treatable cause of progressive paraparesis in patients with a variety of hematological disorders. Since 1956 there have been more than 50 reported cases, most of which occurred in association with thalassaemia. In spinal cord compression secondary to EMH, the lesions are commonly localized to the mid-lower thoracic region.     

Expression of selectin ligands on murine effector and IL-10-producing CD4+ T cells from non-infected and infected tissues

Endothelial selectins are crucial for the recruitment of leukocytes into sites of inflammation. On T cells, ligands for selectins become induced upon differentiation into the effector/memory stage. Initial in vitro studies suggested a correlation between the Th1 phenotype and ligand expression, but whether this also holds true in vivo remained uncertain. We here analyzed selectin ligands on CD4+ T cells producing IFN-gamma, IL-4 or IL-10, prototypic cytokines of the Th1, Th2 and Tr1 subset, respectively. We analyzed mice infected with influenza virus, the bacterium Listeria, and the parasites Toxoplasma (all Th1 models) or Nippostrongylus (Th2 model). A link between the Th1 phenotype and ligand expression was not found in vivo. Surprisingly, the potentially regulatory IL-10-producing T cells displayed the highest frequency of ligand-positive cells in general. Within the inflamed tissues, the frequencies of P-selectin-binding cells increased in the dominant subset, either Th1 or Th2. Up-regulation was also found for E-selectin ligands during influenza, but not Nippostrongylus infection. In conclusion, conditions driving T cell polarization into either Th1 or Th2 in vivo do not affect the expression of selectin ligands, but acquisition of P-selectin binding and hence migration into inflamed tissues is boosted by an inflammatory milieu.     

High rates of clustering of strains causing tuberculosis in Harare, Zimbabwe: a molecular epidemiological study

We examined the pattern of tuberculosis (TB) transmission (i.e., reactivation versus recent transmission) and the impact of human immunodeficiency virus (HIV) infection in Harare, Zimbabwe. Consecutive adult smear-positive pulmonary TB patients presenting to an urban hospital in Harare were enrolled. A detailed epidemiological questionnaire was completed, and tests for HIV type 1 and CD4 cell counts were performed for each patient. Molecular fingerprinting of the genomic DNA recovered from cultures of sputum was performed by two molecular typing methods: spacer oligonucleotide typing (spoligotyping) and analysis of variable number of tandem DNA repeats (VNTRs). A cluster was defined as isolates from two or more patients that shared the same spoligotype pattern or the same VNTR pattern, or both. DNA suitable for typing was recovered from 224 patients. The prevalence of HIV infection was 79%. Of 187 patient isolates (78.6%) typed by both spoligotyping and analysis of VNTRs, 147 were identified as part of a cluster by both methods. By spoligotyping alone, 84.1% of patient isolates were grouped into 20 clusters. The cluster size was generally <8 patient isolates, although three large clusters comprised 68, 25, and 23 patient isolates. A total of 89.4% of the patient isolates grouped into 12 clusters defined by analysis of VNTRs, with 2 large clusters consisting of 127 and 13 patient isolates, respectively. Thirty-six percent of patient isolates with a shared spoligotype and 17% with a shared VNTR pattern were geographically linked within Harare, but they were not linked on the basis of the patient's home district. In a multivariate analysis, there were no independent predictors of clustering, including HIV infection status. Comparison with the International Spoligotype database (Pasteur Institute, Pointe a Pitre, Guadeloupe) demonstrated that our three largest spoligotype clusters are well recognized and ubiquitous in Africa. In this epidemiologically well characterized urban population with a high prevalence of HIV infection, we identified a very high level of strain clustering, indicating substantial ongoing recent TB transmission. Geographic linkage could be detected in a proportion of these clusters. A small group of actively circulating strains accounted for most of the cases of TB transmission.     

Neues zur Pathogenese prim?r systemischer Immunvaskulitiden

Primary systemic vasculitides are defined according immunopathological features and the size of the involved vessels. Three anti-neutrophil cytoplasmic autoantibody (ANCA) associated small vessel vasculitides (Wegener’s granulomatosis, Churg-Strauss syndrome, microscopic polyangiitis) can be distinguished from the so-called Non-ANCA-associated vasculitides, i.e. granulomatous vasculitides of large vessels (giant cell arteritis, Takayasu arteritis) and immune complex-mediated vasculitides of medium-sized and small vessels (Polyarteriitis nodosa, Kawasaki disease and Henoch-Schönlein purpura, cryoglobulinemic vasculitis, cutaneous leukocytoklastische angiitis). Predisposing genetic and other endogenous and exogenous factors facilitate the activation of innate immunity and induce persisting inflammatory reactions resulting in different forms of (auto)-immune vasculitides.