Multiple sclerosis and Chlamydia pneumoniae.
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Biomedical subjects
Publications and source records attributed to J Treib.
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Several authors have reported a chronic fatigue-like syndrome in patients that have suffered from Lyme borreliosis in the past. To further investigate this suspicion of an association without sample bias, we carried out a prospective, double-blind study and tested 1, 156 healthy young males for Borrelia antibodies. Seropositive subjects who had never suffered from clinically manifest Lyme borreliosis or neuroborreliosis showed significantly more often chronic fatigue (p = 0.02) and malaise (p = 0.01) than seronegative recruits. Therefore we believe it is worth examining whether an antibiotic therapy should be considered in patients with chronic fatigue syndrome and positive Borrelia serology.
Hydroxyethyl starch (HES) is one of the most frequently used plasma substitutes. A variety of different HES solutions exist worldwide, which differ greatly in their pharmacological properties. HES is classified according to its manufactured or in vitro molecular weight (MW) into high MW (450-480 kDa), medium MW (200 kDa), and low MW (70 kDa) starch preparations. However, this is not sufficient, because as HES is metabolized in vivo, its MW changes, and it is the in vivo MW which is responsible for the therapeutic and adverse effects of each HES. The rate of metabolization depends mainly on the degree of hydroxyethyl substitution (ranging from 0.4 to 0.7), and the C2/C6 ratio of hydroxyethylation. A high degree of substitution and a high C2/C6 ratio lead to a slow metabolization of HES, resulting in a large in vivo MW. Slowly degradable high MW HES 450/0.7 and medium MW HES 200/0.62 have a high in vivo MW and are eliminated slowly via the kidneys. As a result, these starches have a relatively long-lasting volume effect. When infusing higher volumes (>1500 ml) are infused, large molecules accumulate in the plasma. This can result in bleeding complications due to decreased factor VIII/von Willebrand factor, platelet function defects, incorporation into fibrin clots, and an unfavorable effect on rheological parameters. Rapidly degradable medium MW HES 200/0.5 or low MW HES 70/0.5 are quickly split in vivo into smaller, more favorable molecule sizes, resulting in faster renal elimination, shorter volume effect, and fewer adverse effects on coagulation and rheological parameters. For historical and marketing reasons, only slowly degradable, high MW HES (480/0.7) is available in the United States. In Europe, a large variety of HES solutions are available, dominated by medium MW, easily degradable HES (200/0.5). Because of increasing international competition and the availability of newly developed starches, it is important to be aware of the pharmacological properties of HES and the advantages and disadvantages of the individual preparations.
The goal of the present study was to investigate whether a direct association exists between false-positive recognition of IgG antibodies and inflammatory changes in the central nervous system (CNS) and whether inflammatory diseases of the CNS affect the specificity of the enzyme-linked immunosorbent assay (ELISA) of tick-borne encephalitis (TBE) virus. A group of patients (1,815), treated in the Department of Neurology, University Hospital of the Saarland, Homburg/Saar, Germany, were tested forTBE IgG antibodies by ELISA. Several subgroups of patients with and without inflammatory changes in the CSF as well as patients with and without confirmed multiple sclerosis (MS) were investigated. Overall, 4.5% of all the 1,815 patients and 4.8% of the patients with inflammatory changes in the CSF but without MS had TBE IgG antibodies. In the subgroup with inflammatory changes in the CSF and MS, 4.4% of the patients were TBE IgG-positive. In the subgroup without inflammatory changes in the CSF, 3.8% of the patients without MS were TBE IgG-positive and 4.9% of the patients with MS were TBE IgG-positive. The rate of TBE IgG positivity was not significantly different in the subgroups with and without inflammatory changes in the CSF (P = 0.45). The comparison of the subgroups with and without MS showed no significant difference in the TBE IgG titer (P = 0.83) as well. This indicates that the specificity of the ELISA was affected neither by inflammatory changes in the CSF nor by MS.
Neuroborreliosis is a very frequent subtype of infection with Borrelia burgdorferi. Because of the widely spread inapparent infections finding of diagnosis by analysis of serum antibodies is very difficult. In the years 1990-1994 the serum of 6.775 patients of the Department of Neurology in Homburg, Germany was analysed with regard to Borrelia burgdorferi specific IgG antibodies. 24% showed a positive serum titer and 20% a borderline result. 73 patients showed a specific intrathecal IgG antibody synthesis. In contrast to patients with antibodies in serum these patients showed a significant cumulation during summer. The high percentage of positive serum titers and the season independence support the assumption of widely spread inapparent infections. If a patient shows neurological symptoms the finding of serum antibodies against Borrelia burgdorferi is not sufficient for the diagnosis of Neuroborreliosis. A specific intrathecal synthesis of antibodies, is the most reliable serological indicator for Neuroborreliosis. Intrathecal synthesis usually starts three to four weeks after the first clinical symptoms.
HES are high-polymeric glucose compounds obtained via hydrolysis and subsequent hydroxyethylation from the highly-branched amylopectin contained in maize. Initially, the HES were only characterized by their in vitro molecular weight (Mw), without consideration of the in vivo hydrolysis by alpha-amylase. The degree of substitution and the molar substitution ratio quantify the hydroxyethylation. The glucose units can be substituted at carbon 2, 3 and 6 leading to various substitution patterns. This pattern is described with the C2/C6 hydroxyethylation ratio. The higher the degree of substitution and the C2/C6 ratio, the less the starch is metabolized. The in vitro Mw, the degree of substitution and the C2/C6 ratio are the main determinants of the in vivo Mw which is clinically relevant. Haemorrhagic complications that occur after infusing larger volumes of HES can be avoided with a starch of low in vivo Mw. This is not only due to a lesser effect on the coagulation system which prevents an acquired type I von Willebrand syndrome, but also to a smaller decrease in platelet volume, since platelet volume and platelet function are positively correlated. In addition, HES with low in vivo Mw has significantly better rheological effects than HES with a high in vivo Mw, as high Mw macromolecules affect plasma viscosity negatively. Furthermore high Mw HES macromolecules lead to a distinctive decrease in fibronectin concentration that reflects saturation of the reticuloendothelial system. Another advantage of low in vivo Mw HES is its rather short half-life. Patients with an increased bleeding risk, microcirculatory disturbance or affected RES should receive HES with low in vivo Mw. In the future, HES should be mainly characterized by the in vivo and not the in vitro Mw.
Within the last few years, an increase in cases of tick-borne encephalitis (TBE) as well as an expansion of TBE-endemic regions have been noted in southern Germany. In 1994, a patient was diagnosed for the first time with TBE that had been acquired in Saarland. Up to this point, the Saarland had been considered TBE-free. In a retrospective study, we tested serum samples from 904 patients with abnormalities in the cerebrospinal fluid (CSF) for TBE antibodies. The IgG ELISA used (Immunozym-FSME-IgG, Immuno GmbH, Heidelberg, Germany) yielded 47 positive and 134 borderline sera. The percentage of positive sera showed a significant increase during the time period studied (1989-1994): One IgG-positive serum sample was also IgM-positive. Of the CSF samples, 2 were IgG-positive and 7 were borderline for IgG. In three patients, a positive intrathecal antibody index (IAI) was found, indicating an incrathecal antibody production. An analysis of the vaccination history of the patients showed that only 19% of the patients with a positive TBE IgG titre and only 5.9% of the borderline patients had been vaccinated against TBE. We compared 98 patients that tested positive or borderline for TBE IgG with 98 sex-and-age-matched patients that tested negative. The parameters studied included the patient's complaints upon discharge, the average duration of stationary treatment and 16 different neurological symptoms. We did not observe any significant differences between the two groups. We also tested the sera of 704 of the 904 patients for antibodies to Borrelia burgdorferi (Borrelia burgdorferi ELISA, Genzyme Virotech GmbH, Rüsselsheim, Germany). 155 (22.0%) of the sera were IgG-positive, 136 (19.3%) were borderline, 32 patients (4.6%) had a positive intrathecal antibody index (IAI). The fact that no patient with a clinically manifest case of TBE had acquired the disease in the Saarland indicates that the actual risk of acquiring an acute TBE in the Saarland is very low, despite the high percentage of samples that tested positive for IgG in the ELISA. The increase in the number of serum samples that tested positive for TBE IgG during the last years could be explained by an expansion of TBE regions into the Saarland, increasing vaccination of the population or more travel to endemic regions. The proportion of patients with IgG antibodies to Borrelia was 22%. Because only part of the patients suffered from an acute, clinically manifest borreliosis, and since the serum IgG titre had remained positive for many years after contact with the microorganisms, we suspected that a large percentage of the population would show signs of a clinically silent infection in their sera. 4.6% of the patients had a positive IAI quotient, a clear indication of neuroborreliosis.
In stroke penumbra perfusion depends passively on hemodynamics. So far hemodynamic effects of low molecular weight hydroxyethylstarch (HES) has not been investigated. Ten stroke patients received hypervolemic HES therapy. Cardiac output and heart rate were monitored using the bioimpedance method, blood pressure by conventional measurement. The Scandinavian Stroke Scale assessed clinical outcome. Circadian cardiac output changes were measured in 20 controls. Patients' cardiac output increased after the loading dose (5.3 +/- 1.4 l min(-1) to 6.5 +/- 1.7 l min(-1), p < 0.01), fluctuating then between 5 and 7 l min(-1) without nocturnal decrease. Beside an initial increase, the heart rate showed, like blood pressure, no remarkable changes. The Scandinavian Stroke Scale score did not change significantly. The controls showed a circadian cardiac output fluctuation (2.00 am, 5.3 +/- 0.3 l min(-1); 8.30 am, 8.1 +/- 0.6 l min(-1). Our patients showed a hemodynamic and clinical stabilization under therapy with low molecular weight HES. The physiological nocturnal decrease of cardiac output and blood, which might cause clinical deterioration in stroke patients, was avoided.
Perfusion is thought to be impaired in brain edema due to reduced perfusion pressure. Brain edema therapy is assumed to improve perfusion. We assessed regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV) and mean transit time of blood (MTT) using perfusion-weighted magnetic resonance imaging (MRI) in 15 patients showing acute local brain edema due to infarction or intracerebral hematoma. Patients were treated by intravenous infusion of 125 ml 40% sorbitol over 10 min. rCBF, rCBV and MTT in the edematous region were measured before and 30 min after treatment. Before treatment rCBF (46.5 +/- 12.1 vs. 42.9 +/- 10.5 ml 100 g-1 min-1), MTT (4.7 +/- 1.9 vs. 4.0 +/- 1.7 s) and rCBV (5.4 +/- 1.7 vs. 4.7 +/- 1.1 ml 100 g-1) were significantly (p < 0.05) increased in the edematous region compared to the contralateral side. After treatment no significant differences could be found. We interpret the elevation of MTT and rCBV in the edema as signs of an autoregulative compensation of an impaired perfusion. rCBF is even over-compensated. After brain edema therapy perfusion seems normalised. This new MRI method appears as useful for measuring therapeutic effects on cerebral perfusion.
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INTRODUCTION: The noninvasive management of the conservative therapy for intracranial pressure (ICP) with hyperosmolar substances is a central problem in the treatment of brain edema. Using transcranial Doppler (TCD), a continuous monitoring of ICP is now possible, because the TCD pulsatility index (PI) intraindividually closely correlates with the level of ICP. PATIENTS AND METHODS: We administered an ICP-lowering treatment 113 times in 10 patients with intracranial bleeding or ischemic stroke who also had signs of elevated ICP in the computer tomogram. The treatment was carried out over a period of 9 days, using 50 g each of intravenous sorbitol (n = 38) and mannitol (n = 32) or oral glycerol (n = 43). RESULTS: PI was significantly lowered between 20.0 and 23.9% (p < 0.01) by all substances in the affected and unaffected sides. The differences between the three substances and the differences between the affected and unaffected sides were not significant. The duration of the therapeutic effect of glycerol (190 +/- 41 min) was significantly longer (p < 0.01) than that of sorbitol (150 +/- 28 min) or mannitol (130 +/- 20 min). The duration of the therapeutic effect was also significantly shorter (p < 0.01) in patients with a high PI (> 1.5). All three substances led to a significant increase (p < 0.01) in minimal (= diastolic) flow velocity (Vmin). The increase was highest for glycerol (56.3 +/-72.6%). SUMMARY: The decrease in PI under therapy was caused by an increase in Vmin. This indicates that ICP therapy with hyperosmolar substances improves brain edema and does not suggest a therapy-induced vasoconstriction.
Systematic studies of a possible human neuropathogenicity of the Erve virus have not yet been carried out. In a randomized, blind study 166 patients with viral encephalitis, 46 patients with cerebral hemorrhage, 72 patients with "thunderclap" headache, and 205 healthy blood donors were examined by indirect immunofluorescence for Erve virus antibodies. None of the patients with encephalitis, two patients with cerebral hemorrhage (4.3%), 10 patients with thunderclap headache (13.9%; p < 0.0001), and two blood donors (1.0%) exhibited antibodies against the Erve virus. These results suggest a human pathogenicity of the Erve virus for the first time.
The authors performed a clinical and serologic follow-up study after 4.2 +/- 1.2 years in 44 patients with clinical signs of neuroborreliosis and specific intrathecal antibody production. All patients had been treated with ceftriaxone 2 g/day for 10 days. Although neurologic deficits decreased significantly, more than half the patients had unspecific complaints resembling a chronic fatigue syndrome and showed persisting positive immunoglobulin M serum titers for Borrelia in the Western blot analysis.
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