Lebensqualität polytraumatisierter Patienten 2 Jahre nach Unfall

Objective:

The present study analyses long-term survival, functional outcome and quality of live 2 years after trauma.

Patients and methods:

The complete consecutive data sets of patients admitted through the ER from 8/1998 until 8/2000 was documented and analyzed by a standardized protocol (GOS: Glasgow Outcome Score, SF-36, EuroQuol) precisely 2 years after trauma. 2-year mortality was based on the information provided by family physicians and community officials.

Results:

A total of 482 patients (mean ISS 24) was prospectively included (mean age 39 years). 2 years after trauma 26% had died. 68% were fully rehabilitated according to GOS, the rest remained severely disabled whereof 13% needed permanent care. EuroQuol and SF-36 revealed chronic pain and anxiety states in >50% of the patients. Everyday activities and mobility were permanently impaired in 40–50%. The social situation after trauma included increased unemployment (5% to 13,5%), disablement (0% to 15,3%), retraining (9,9%) and job changes (15,8%). Very often (30%) patients had to tolerate significant financial losses. Private live and family situation was seemingly unchanged.

Conclusions:

Patients after severe multiple trauma often suffer from significant psychophysical and socioeconomic impairment requiring adequate treatment and care from both health system and family resources. Based on structured early rehabilitation and occupational reintegration a coherent, long-term restructuring effort is needed for these patients.     

Epstein-Barr virus-associated B-cell lymphoproliferative disorders in angloimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, unspecified

Various patterns of Epstein-Barr virus (EBV)-associated B-cell lymphoproliferation occur in patients with immunodeficiency. We studied 17 cases of T-cell lymphoma displaying extensive EBV-driven B-cell lymphoproliferation or simultaneous/subsequent EBV-associated B-cell lymphoma. In 10 cases of angioimmunoblastic T-cell lymphoma, an uncommonly prominent population of EBV+ atypical, activated, focally confluent large transformed B cells was found in the background of T-cell lymphoma. In 4 cases, an EBV-associated B-cell neoplasm (3 diffuse large B-cell lymphomas, 1 plasmacytoma) occurred in patients with T-cell lymphoma. Three cases were composite lymphomas of a peripheral T-cell lymphoma, unspecified, combined with EBV-associated diffuse large B-cell lymphoma. The transformed B-cell population displayed EBV latency types 2 and 3. Monoclonal and oligoclonal B-cell populations were detected in 5 and 6 cases, respectively. Similar to other states of immunodeficiency, disease-related and therapy-induced immunosuppression in T-cell lymphoma may lead to a prominent EBV-associated B-cell lymphoproliferation and to EBV+ B-cell neoplasms.     

Long-Term Growth Selection of Mice Changes the Intrinsic Susceptibility of Myogenic Cells to Apoptosis

Myogenic cells were derived from mice long-term selected over 70 generations for high 6-weeks body weight (DU-6) and from unselected control mice (DU-Ks). The cells were grown in medium with 10% foetal bovine serum (FBS) for 8 days or transferred to low serum conditions (1% FBS) at days 4 and 6 of cultivation, respectively, and maintained for two further days. In both cell lines, serum reduction induced decreases in DNA and protein contents, and in DNA synthesis rate. It also triggered apoptotic cell death as demonstrated by increased DNA strand breaks and expression of active caspase-3. Concomitantly, the anti-apoptotic protein bcl-2 was enhanced. The basal frequency of apoptotic cells decreased with time of cultivation in both lines and was lower in DU-6 than in DU-Ks cells. However, the increase in apoptosis induced by serum reduction was more pronounced in DU-6 than in DU-Ks cells and did not differ between the time points of serum reduction. The results suggest that growth selection decreases the basal apoptosis frequency of muscle satellite cells under normal supply, but enhances the intrinsic susceptibility to growth factor withdrawal by serum deprivation as a severe apoptotic stimulus. Furthermore, the apoptotic response to growth factor withdrawal seems to be largely independent of the stage of myogenic development.     

Chromosomal gains at 9q characterize enteropathy-type T-cell lymphoma

Genetic alterations in enteropathy-type T-cell lymphoma (ETL) are unknown so far. In this series, 38 cases of ETL were analyzed by comparative genomic hybridization (CGH). CGH revealed chromosomal imbalances in 87% of cases analyzed, with recurrent gains of genetic material involving chromosomes 9q (in 58% of cases), 7q (24%), 5q (18%), and 1q (16%). Recurrent losses of genetic material occurred on chromosomes 8p and 13q (24% each), and 9p (18%). In this first systematic genetic study on ETL, chromosomal gains on 9q (minimal overlapping region 9q33-q34) were found to be highly characteristic of ETL. Fluorescence in situ hybridization analysis on four cases of ETL, using a probe for 9q34, indicated frequent and multiple gains of chromosomal material at 9q34 (up to nine signals per case). Among 16 patients with ETL who survived initial disease presentation, patients with more than three chromosomal gains or losses (n = 11) followed a worse clinical course than those with three or less imbalances (n = 5). The observation of similar genetic alterations in ETL and in primary gastric (n = 4) and colonic (n = 1) T-cell lymphoma, not otherwise specified, is suggestive of a genetic relationship of gastrointestinal T-cell lymphomas at either localization.     

Regulatory T cell-derived interleukin-15 promotes the diversity of immunological memory

While the immunosuppressive function of regulatory T (Treg) cells has been extensively studied, their immune-supportive roles have been less well investigated. Using a lymphocytic choriomeningitis virus (LCMV) Armstrong infection mouse model, we found that Treg cell-derived interleukin (IL)-15 is required for long-term maintenance of the KLRG1⁺IL-7Rα⁻CD62L⁻ terminal effector memory CD8⁺ T (tTEM) cell subset, but dispensable for the suppressive function of Treg cells themselves. In contrast, deletion of Il15 from other sources, including myeloid cells and muscles, did not affect the composition of the memory CD8⁺ T cell pool. Our findings identify Treg cells as an essential IL-15 source maintaining tTEM cells and suggest that Treg cells promote the diversity of immunological memory.     

High frequency of genetic aberrations in enteropathy-type T-cell lymphoma

To define genetic aberrations playing a role in the development of enteropathy-type T-cell lymphoma (ETL), we examined 26 such tumors using a battery of 47 microsatellite markers. The most frequent aberration (seen in 40% of informative genotypes) was amplification of genomic material in region 9q34 encompassing c-abl and Notch-1 gene loci. Other frequent amplifications were detected in regions 5q33.3-34 and 7q31 (both in more than 30%). Multiple losses of heterozygosity were detected in 6p24, 7p21, 17q23-25, regions containing putative tumor suppressor genes, and in the p53 locus in 17p13.1. Analysis of the pattern of occurrence of these aberrations revealed existence of two ETL subgroups: one of them characterized by the 9q34 aberration and another smaller one showing allelic imbalances in 3q27. These two aberrations were mutually exclusive. Microsatellite instability (MSI) was detected in 69% of the examined lymphomas; the percentage of MSI-positive genotypes per tumor ranged from 2% to 12%. The spectrum of genetic alterations detected showed patterns dependent on morphology. Monomorpic ETLs displayed frequently biallelic TCR-gamma gene rearrangement (p = 0078, chi(2) test). They showed a different pattern and fewer allelic imbalances (no 3q27, 4q28, 13q14, fewer 5q21, or 5q33.3-34 aberrations) and a lower frequency of MSI than pleomorphic ETLs.     

Therapeutic apheresis in myasthenia gravis patients: a six year follow-up.

Six years ago 4 patients suffering from myasthenia gravis (MG) types C and E according to Compston with failed drug therapy were initially treated 3 times (1 patient, a total of 11 times) by protein A immunoadsorption (Immunosorba, Excorim AB, Lund, Sweden). No further immunoadsorption treatments have been carried out. In addition, 3 patients were given a thymectomy. The present status of the patients was checked. We could see a beneficial effect in all MG patients. The patients are fit for work; each has an improved Besinger index. The patients were used as their own controls. A higher anti-AChRAb level 6 years after protein A immunoadsorption than at the beginning was seen in all patients, combined with less serious MG. In addition, their immunomodulation could be induced as seen in lymphocyte and inflammatory protein changes during the first 36 days after beginning immunoadsorption treatment. A larger population has to be investigated to verify these results.     

Intravenous immunoglobulins as therapeutic option in the treatment of multiple sclerosis

Journal of Neurology - Treatment of neurological disorders with intravenous immunoglobulin (IVIG) is an increasing feature of practice for an expanding range of indications. This article reviews...     

Bcl-2 expressing T lymphocytes in multiple sclerosis lesions

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. T lymphocytes play a major role in the pathogenesis of the disease. The exact mechanisms by which the inflammation is regulated in MS have not yet been defined. Studies in animal models of MS suggest that apoptosis of T  cells is the main factor terminating inflammation. The process of apoptosis itself is regulated by a range of pro- and anti-apoptotic proteins. The bcl-2 gene family is an important member of these proteins. The present study investigated the expression of the anti-apoptotic protein bcl-2 in 11 chronic MS cases including five relapsing-remitting and six chronic progressive MS patients. A total of 35 lesions containing all stages of demyelinating activity were studied. The number of CD3-positive T  cells and the absolute and relative numbers of T  cells expressing bcl-2 were determined by double immunocytochemistry. Bcl-2 is expressed by T lymphocytes in MS plaques. Patients with chronic progressive MS have a higher proportion of bcl-2 expressing T  cells than patients with relapsing remitting disease. Highest numbers of bcl-2-positive T lymphocytes were found in remyelinating and demyelinated lesions, whereas active demyelinating lesions revealed lower numbers. These data indicate that cell-death-related proteins such as the anti-apoptotic protein bcl-2 are expressed in MS lesions and that they might have important effects on the regulation of elimination or persistence of inflammatory cells in the central nervous system.