Immigrants to Germany and their children are at particular risk for tuberculosis (TB). -
35 Patients (10 male / 25 female aged 2 - 59 years (median 33 years) originating mostly from high incidence ...countries in Asia (19 (54.3%)) in Africa (14 (40.0%) and East Europe (2 (5.7%)), attended at the Tropical Medicine Unit were analysed. -
Primary clinical presentation was most frequently lymphadenitis (13 (37.1%)). Other organs involved included bones (7 (20.0%)), central nervous system (5 (14.3%)), urogenital organs (3 (8.6%)), lung (3 (8.6%)), mediastinum, (2 (5.7%)) and abdomen (2 (5.7%)). ESR was abnormal in 21/28 (75.0%), CRP in 20/35 (57.1%), and protein electrophoresis in 22/26 (84.6%) cases. The tuberculin skin test was strongly positive in all 15 cases where the test had been performed. Tuberculosis interferon gamma release assay (TB-IGRA) was positive in all 35 cases (100%). PCR for nucleic acids of Mycobacterium (M.) tuberculosis complex was positive in only 7/20 (35.0%) cases. M. tuberculosis was identified in 32/35 (91.4%), M. bovis in 2 (5.7%) cases. 1 case was diagnosed clinically. All patients were negative for HIV. Typical histopathology was seen in the 29 cases, where biopsies had been taken. Chest-X-ray did not reveal specific pulmonary lesions in the majority of cases (22/35 (62.9%)). Diagnosis of TB was mostly delayed (4 to 299 weeks, (median 8)). The most frequent primary suspicion was a malignancy (17/35 (48.6%)) while TB was initially suspected in 5 cases only. Diagnosis of TB is impeded by its multifaceted presentation especially in immigrants.
The updated recommendations presented here reflect new developments in the diagnostic work-up and immunotherapy of multiple sclerosis (MS) as well as optimization of medical care for MS patients. ...Monoclonal antibodies provide considerable improvement of treatment, but their use in basic therapy is restricted by their side effect profile. Thus, for the time being, natalizumab is only approved for monotherapy after basic treatment has failed or for rapidly progressive relapsing-remitting MS. In contrast, long-term data on recombinant beta-interferons and glatiramer acetate (Copaxone) show that even after several years no unexpected side effects occur and that a prolonged therapeutic effect can be assumed which correlates with the dose or frequency of treatment. Recently IFN-beta1b (Betaferon) was approved for prophylactic treatment after the first attack (clinically isolated syndrome, CIS). During treatment with beta-interferons, neutralizing antibodies can emerge with possible loss of effectivity. In contrast, antibodies play no role in treatment with glatiramer acetate. During or after therapy with mitoxantrone, serious side effects (cardiomyopathy, acute myeloid leukemia) appeared in 0.2-0.4% of cases. Plasmapheresis is limited to individual curative attempts in escalating therapy of a severe attack. According to the revised McDonald criteria, the diagnosis of MS can be made as early as the occurrence of the first attack (CIS). Recommendations for optimized care of MS patients are also new, thus implementing a resolution of the European Parliament.
Background: Axonal damage is the main cause for permanent disability in patients with multiple sclerosis (MS), the most common chronic inflammatory CNS disorder in young adults. The majority of ...studies in the past focussed on the involvement of CD4+ T cells in MS pathogenesis both in humans as well as in the animal model of MS, experimental autoimmune encephalomyelitis (EAE). Objective: Although several recent findings demonstrated the involvement of CD8+ T cells in MS and established a pathogenic role of myelln-specific CD8+ T cells in the animal model, mechanistic insights into CD8-driven CNS damage are lacking. Methods: To observe the interactions between antigen-specific T cells and their targets in living brain tissue, we applied a quasi-in vivo confocal imaging approach of organotypic brain slices derived from transgenic mice. In this setting, we used both CD8+ T cells (CTL) and CD4+ T cells carrying transgenic T cell receptors specific for the same antigen as effector cells. Results: While we could clearly demonstrate the capacity of CTLs to damage myelinated axons pulsed with cognate antigen, it remains unresolved to this date, whether axonal injury is the result of a targeted hit against the axon itself or the consequence of an attack against the myelin structure (collateral damage). To specifically answer this question, we next restricted the transgenic expression of the cognate antigen exclusively to the cytosol of oligodendrocytes. Conclusions: Here, we could unambigously show that axonal injury is the result of "collateral damage" by antigen-specific CTL targeting their cognate antigen presented by oligodendrocytes.
The role of free radicals and oxidative stress in neurological disorders has only recently been recognized, leaving clinical neurologists to seek in vain for information on the subject even in major ...textbooks. What published information there is may consist of brief reminders of the possible association of superoxidase dismutase with familial amyotrophic lateral sclerosis and nitrous oxide with migraine. With luck they may also find information on the purported role of free radicals in the pathogenesis of traumatic brain injury. Oxidative Stress and Free Radical Damage in Neurology sets the record straight, focusing on clinical and research issues regarding the interplay of free radicals and the human nervous system. Crucially, the chapters cover numerous antioxidants and their possible therapeutic role in neurological disorders. Key illnesses such as epilepsy, multiple sclerosis and Parkinson's are analyzed, and chapters also examine more general issues such as the link between free radicals and inflammation of the central nervous system. Clinicians and laboratory researchers alike will find that this book augments their understanding not only of the widespread involvement of free radicals in the central nervous system but also of some uncertainties surrounding whether free radical damage in neurology plays a primary or secondary role.
Urea cycle defects belong to the most common metabolic disorders with a cumulative incidence of 1:8000. A common trait of urea cycle defects is a disturbed detoxification of ammonia leading to ...hyperammonemia in the event of a high nitrogen load. Most patients develop symptoms in the neonatal period or in infancy, e. g. vomiting, seizures and disturbed consciousness. Depending on the affected enzyme and its residual activity, patients differ in the age at first presentation, the character and severity of symptoms and in the susceptibility to metabolic derangement. The presence of hyperammonemia and an altered plasma amino acid profile give the essential diagnostic clues. Since modern therapeutic measures have prolonged the life expectancy of these patients and provided the possibility of a first presentation in adulthood, patients with urea cycle defects have become an increasing challenge in internal medicine. The reported case series illustrates the heterogeneous clinical course of these disorders from childhood to adulthood.
Autoimmune T cells play a key role as regulators and effectors of autoimmune disease. In multiple sclerosis (MS), activated T cells specific for myelin components or other locally expressed ...autoantigens enter the CNS and recognize their antigen(s) on local antigen-presenting cells. After local stimulation, the T cells produce a plethora of cytokines and inflammatory mediators that have profound effects on the local cellular environment, induce and recruit additional inflammatory cells, and contribute to myelin damage. An increasingly detailed knowledge of these processes will greatly facilitate the development of new immunotherapies. This article focuses on the role of T cells in MS. We provide a brief overview of the principles of T-cell immunology, discuss the experimental techniques available for studying T cells, address the role of T cells in the pathogenesis of MS, and highlight modern concepts for immunotherapy.
The inflammatory myopathies include dermatomyositis, polymyositis, and inclusion body myositis. In dermatomyositis, muscle fiber injury is secondary to an antibody- or immune-complex-mediated immune ...response against a vascular-endothelial component. In polymyositis and inclusion body myositis, CD8+ T cells and macrophages invade and eventually destroy initially nonnecrotic muscle fibers. The autoaggressive T cells have the phenotype of activated (HLA-DR+) memory (CD45RO+) cells. T-cell receptor analyses indicate that the autoaggressive T cells are oligoclonal. In inflammatory lesions, muscle fibers express various cytoplasmic and surface molecules that are not detectable in normal fibers. These molecules, which include HLA class I antigens, heat-shock proteins, adhesion molecules, and Fas, are probably induced by locally secreted cytokines. The autoaggressive CD8+ T cells harbor granules containing perforin that aggregate near the contact zone with the target muscle fiber. This is consistent with a perforin- and secretion-dependent mechanism of muscle fiber injury. Many invaded muscle fibers also express the Fas "death receptor," but signs of apoptosis are absent.
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