Detection of apoptotic cells in cerebrospinal fluid of patients suffering from neurological disease

Apoptotic elimination of pathogenic immune cells is considered one of several regulatory mechanisms in inflammatory diseases. To explore the potential relationship between detection of apoptotic cells in the cerebrospinal fluid (CSF) and different types of neurological diseases, we examined cellular apoptosis at the stage of DNA fragmentation, defined by morphological criteria and a molecular biology technique (in situ tailing). During a first phase, 3446 CSF samples derived from admitted patients suffering of inflammatory (IND) and non-inflammatory neurological diseases (NIND) were analysed in the course of routine clinical diagnostics. First, all specimens were inspected for cells displaying atypical morphology following established morphological criteria of intact lymphocytes or apoptosis. In a second phase, 76 additional CSF samples collected from individuals according to investigated clinical groups were analysed in parallel by means of in situ tailing, which indicates the advanced degree of apoptotic demise through labelling of controlled DNA fragmentation. No apoptotic processes were detected by either analytical method in CSF of clinically distinct diseases, amongst others multiple sclerosis (MS). This indicates that the detection of apoptotic cells in CSF during clinical routine diagnostics does not have sufficient explanatory power for the investigated conditions. Furthermore, based on immunohistochemistry, the proportion of CSF lymphocytes expressing the pro-apoptotic receptor Fas (CD95) tended to be higher in NIND patients compared to patients with other IND and MS, but the difference was not statistically significant. In contrast, expression of the anti-apoptotic protein Bcl-2 did not differ between investigated patient groups.     

Immunology and neurology

The classical field of neuroimmunology deals with the immune response in infectious, autoimmune-mediated, ischemic, degenerative, traumatic, and neoplastic diseases of the nervous system with a major focus on immune-mediated demyelination. Recently more and more evidence points to a broader interaction between the immune and nervous systems via morphological connections, shared signal molecules and common mechanisms of signal transduction. Consequently, immune processes affect nervous functions and vice versa under both physiologic and pathologic conditions. This includes neuroendocrine (hormonal) and vegetative (neurotransmitter-mediated) influences on the immune response including conditioned immunostimulation and immunosuppression (neuroimmunomodulation) as well as effects of immune mediators (cytokines) on neuronal and psychic functions (psychoneuroimmunology). These findings have a strong impact on future strategies for the treatment of somatic as well as psychiatric diseases.     

Complementary and alternative medicine and coping in neuroimmunological diseases

The utilisation of complementary and alternative medicine (CAM) is widespread in neuroimmunological diseases like multiple sclerosis (MS) but has been disregarded in research until lately. After describing the problems of definition in CAM, different categories will be described. Various confounding factors on CAM utilisation exist, though hardly investigated. Besides sociodemographic variables like education, income, gender and age, illness-related factors like severity of disease are discussed. Furthermore, the important role of coping and CAM utilisation has not been investigated in neuroimmunological diseases, yet. Results derived from our investigations on CAM utilisation in MS indicate that users of CAM apply coping strategies, such as "rumination", "search for information" and "search for meaning in religion", more frequently than non-users and that current CAM utilisation is related to depression. Further research is needed in this field, as well as in other neuroimmunological diseases.     

Lymphocyte Subpopulations,Oxidative Burst and Apoptosis in Peripheral Blood Cells of Patients with Multiple Sclerosis–Effect of Interferon-β

At present, the most efficient therapeutical treatment of multiple sclerosis (MS) is achieved by IFN-β. However, its in vivo effects remain incompletely understood. If applied parenterally, the hydrophobic IFN-β acts primarily on blood cells with probable selectivity for functionally different lymphocyte subpopulations, monocytes and granulocytes. We have investigated the expression of the activation marker interleukin-2 receptor-α (CD25) on CD3⁺ T cells, CD19⁺ B cells, foetal-type γδ⁺CD3⁺ T cells and foetal-type CD5⁺CD19⁺ B cells of the peripheral blood. In addition, the oxidative burst activity and apoptosis have been determined in mononuclear and polymorphonuclear blood cells, respectively. The study accompanied a phase III trial with IFN-β1b (BETAFERON^®, Schering). Two groups of MS patients with relapsing-remitting course of the disease have been investigated at 8 time points (days 0, 5, 15, 31, 60, 90, 180 and 270 after starting therapy): (1) verum group (n=8) with application of 8 Mill. units IFN-β1b every other day, and (2) placebo group (n=4) with application of placebo for 3 months and therapy as in (1) from day 90 onward. The main results were: (1) Activated T cells decreased until day 180 in the verum group and return thereafter to pre-treatment values, whereas in the placebo group the values remained relatively stable over the whole observation period. (2) Activated B cells increased between days 90 and 270 in both groups, i.e. after verum application in both groups. (3) Foetal-type B cells were more activated than total B and T cells with increase over time in both groups. (4) Foetal-type T cells exerted relatively stable intra-individual levels with generally low CD25 expression, but punctual CD25 peaks in both groups. (5) The spontaneous oxidative burst was higher in lymphocytes, more variable in monocytes and faster increasing in granulocytes in the verum group than in the placebo group. (6) Apoptosis of mononuclear cells and granulocytes showed similar variations in the verum and placebo groups with the exception of a selective increase over time of the proportion of granulocytes undergoing induced apoptosis in the verum group. It is concluded that IFN-β has the following main effects on the immune system of MS patients: (1) the T cell immunity is systemically and reversibly suppressed, (2) the foetal-type lymphocytes, which are responsible for the first line of defence of infections, are stimulated in the long range, (3) the oxidative burst activity is increased in lymphocytes and granulocytes and instable in monocytes, and (4) the inducibility of apoptosis in granulocytes is increased. Re-examination of the altered blood cell parameters after long-term IFN-β therapy is warranted.     

Results of titanium locking plate and stainless steel cerclage wire combination in femoral fractures

Background:

Some in vitro studies warn combining different metals in orthopedic surgery. The aim of this study is to determine the impact of combining titanium and stainless steel on bone healing and the clinical course of patients undergoing internal fixation of femoral fractures.

Materials and Methods:

69 patients with femoral fractures had polyaxial locking plate osteosynthesis. The locking plate was made of a titanium alloy. Two different cohorts were defined: (a) sole plating and (b) additional stainless steel cerclage wiring. Postoperative radiographs and clinical followup were performed at 6 weeks, 3 months and 12 months.

Results:

Cohorts A and B had 36 and 33 patients, respectively. Patient demographics and comorbidities were similar in both groups. In two cases in cohort A, surgical revision was necessary. No complication could be attributed to the combination of titanium and stainless steel.

Conclusion:

The combination of stainless steel cerclage wires and titanium plates does not compromise fracture healing or the postoperative clinical course.     

Composite lymphoma: the interface between Hodgkin's and non-Hodgkin's lymphoma

Hodgkin's lymphoma is a rare neoplasm mainly affecting young people. Within the last decade, nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL) has been separated from all other cases of the so-called classical type. Moreover, the derivation of Hodgkin's lymphoma from germinal centre B-cells has been established, giving rise to a possible clonal relationship between Hodgkin's lymphoma and the non-Hodgkin's lymphomas (NHLs). The interface between them therefore has both diagnostic and biological aspects. Diagnostic difficulties arise, due to overlapping definitions, between biologically unrelated entities, e.g. classical Hodgkin's lymphoma and NLPHL or anaplastic large cell lymphoma, respectively. On the other hand, there is a biological grey zone regarding composite lymphomas consisting of Hodgkin's lymphoma and any NHL. This simultaneous or subsequent occurrence of Hodgkin's lymphoma and non-Hodgkin's lymphomas may, or may not, be clonally related. For management purposes lymphomas, e.g. NLPHL and T cell-rich B-cell lymphoma, must be distinguished along a continuous spectrum of progression.     

Transcranial brain sonography findings related to neuropsychological impairment in multiple sclerosis

Journal of Neurology - Cognitive dysfunction, fatigue and mood disorder contribute to the neuropsychological impairment that is common in multiple sclerosis (MS). The present paper reviews...