1,721,006 research outputs found
Cerebrospinal Fluid Diagnostics for Neuroinfectious Diseases
No full textCerebrospinal fluid analysis is of prime importance to establish an early diagnosis of central nervous system infections. Beside the basic diagnostics containing CSF white cell count, lactate concentration and protein analysis, the targeted search for agents of bacterial, viral or fungal CNS infectious diseases is essential. Decisive methods are bacterial and fungal staining techniques, microbiological culture methods, nucleic acid amplification and antigen detection methods or indirect identification of pathogens by serologic testings including the determination of pathogen-specific intrathecal immunoglobulin synthesis. Besides imparting basic principles of cerebrospinal fluid analysis, this article focuses on special aspects of detection of infectious agents. Well-directed questions and a close communication between clinician and laboratory allow optimal diagnostic analysis for successful confirmation of the diagnosis and for optimal treatment of the patient
No neuroprotective effect of erythropoietin under clinical treatment conditions in a rabbit model of Escherichia coli meningitis
No full textDespite effective antibiotic treatment, neuronal injury is frequent among children and adults with bacterial meningitis resulting in a high rate of death and neurologic sequelae. The hematopoietic cytokine erythropoietin (EPO) provides neuroprotection in models of acute and chronic neurologic diseases. We studied whether recombinant EPO (rEPO) reduces neuronal damage in a rabbit model of Escherichia coli meningitis. Inflammation within the central nervous system (CNS) was monitored by measurement of bacterial load, pleocytosis, protein, and lactate in the cerebrospinal fluid (CSF). Neuronal damage was measured by quantification of the density of apoptotic neurons in the hippocampal dentate gyrus and the concentration of the global neuronal destruction marker neuronspecific enolase (NSE) in CSF. To increase clinical relevance, rEPO was applied as adjunctive therapy from the beginning of antibiotic therapy 12 h after infection. EPO treatment applied as an intravenous injection at a dose of 1000 IU/kg body weight resulted in plasma concentrations of 6993 +/- 1406 mIU/mL, CSF concentrations of 1291 +/- 568 mIU/mL, and a CSF-to-plasma ratio of 0.18 +/- 0.07 (mean +/- SD) 6 h after injection. Under these treatment conditions, no antiinflammatory or neuroprotective effect of EPO was observed
No neuroprotective effect of erythropoietin under clinical treatment conditions in a rabbit model of Escherichia coli meningitis
No full textDespite effective antibiotic treatment, neuronal injury is frequent among children and adults with bacterial meningitis resulting in a high rate of death and neurologic sequelae. The hematopoietic cytokine erythropoietin (EPO) provides neuroprotection in models of acute and chronic neurologic diseases. We studied whether recombinant EPO (rEPO) reduces neuronal damage in a rabbit model of Escherichia coli meningitis. Inflammation within the central nervous system (CNS) was monitored by measurement of bacterial load, pleocytosis, protein, and lactate in the cerebrospinal fluid (CSF). Neuronal damage was measured by quantification of the density of apoptotic neurons in the hippocampal dentate gyrus and the concentration of the global neuronal destruction marker neuronspecific enolase (NSE) in CSF. To increase clinical relevance, rEPO was applied as adjunctive therapy from the beginning of antibiotic therapy 12 h after infection. EPO treatment applied as an intravenous injection at a dose of 1000 IU/kg body weight resulted in plasma concentrations of 6993 +/- 1406 mIU/mL, CSF concentrations of 1291 +/- 568 mIU/mL, and a CSF-to-plasma ratio of 0.18 +/- 0.07 (mean +/- SD) 6 h after injection. Under these treatment conditions, no antiinflammatory or neuroprotective effect of EPO was observed
Matrix metalloproteinase-9 deficiency impairs host defense mechanisms against Streptococcus pneumoniae in a mouse model of bacterial meningitis
No full textMatrix metalloproteinase-9 (MMP-9) appears to contribute to blood-brain barrier damage and neuronal injury in bacterial meningitis. To further explore the function of MMP-9 in meningeal inflammation, we injected 104 colony forming units (CFU) of a Streptoccocus pneumoniae type 3 strain into the right forebrain of MMP-9 deficient mice (MMP-9(-/-), n = 16) and wild-type controls (129 x B6, n = 15). The clinical course of the disease, leukocyte recruitment into the subarachnoid space and bacterial titers in the brain did not differ. Yet, clearance of the bacteria from blood (log CFU/ml 4.7 [3.8/5.4] vs. 3.6 [3.0/4.0]; P = 0.005) and spleen homogenates (log CFU/ml 5.3 [4.8/5.5] vs. 4.0 [2.8/4.7]; P = 0.01) was reduced in MMP-9 deficient mice. A reduced systemic bacterial clearance of MMP-9(-/-) mice was confirmed in experimental S. pneumoniae peritonitis/sepsis. This implies a compromised systemic, but not intracerebral host response against S. pneumoniae in MMP-9 deficiency. (C) 2002 Published by Elsevier Science Ireland Ltd
Infections in the differential diagnosis of Bell’s palsy: a plea for performing CSF analysis
No full textRifampicin followed by ceftriaxone after one hour reduces the release of toxic and proinflammatory bacterial compounds by Streptococcus pneumoniae in comparison to treatment with the bacteriolytic ceftriaxone alone
No full textUpdate Neuroborreliosis - New and Proven Options
No full textNeuroborreliosis is a nervous system infection caused by Borrelia burgdorferi sensu lato. Lyme disease is the most frequent tick-borne infectious disease in Europe affecting the skin, joints, heart, nervous system and rarely the eyes. Since the discovery of the causative pathogen Borrelia burgdorferi 30 years ago, the rapid accumulation of knowledge about this disease has resulted in well-evaluated clinical and microbiological diagnostic guidelines. Today, neuroborreliosis can generally be diagnosed and treated successfully. Progress in microbiological research has led to improved serological tests with higher sensitivity and new approaches for early diagnosis of Lyme disease. Erythema migrans is the most frequent manifestation of Borrelia infection. It is diagnosed clinically. Neuroborreliosis is diagnosed by the combination of typical neurological symptoms, cerebrospinal fluid pleocytosis and Borrelia-specific antibodies produced intrathecally. In adults, erythema migrans is treated with doxycycline, in children with amoxicillin. Standard treatment of neuroborreliosis is ceftriaxone or cefotaxime i.v. Recent studies show similar efficacy of oral doxycycline in early neuroborreliosis. An appropriate antibiotic treatment eliminates the pathogen effectively. Repeated episodes of acute manifestations of Lyme disease in treated patients are probably due to reinfection and not to relapse. Only in a small proportion of treated patients is recovery from neuroborrelioses incomplete. In addition to neurological residual sequelae recent studies have detected persistent neuropsychological deficits in a small subgroup of patients. Conversely, when borreliosis is suspected by patients suffering from non-specific symptoms, a thorough clinical and laboratory assessment is required to identify other underlying diseases
Rifampicin followed by ceftriaxone after one hour reduces the release of toxic and proinflammatory bacterial compounds by Streptococcus pneumoniae in comparison to treatment with the bacteriolytic ceftriaxone alone
No full textA probable cause of paradoxical thrombosis in zygomycosis
No full textInvasive zygomycoses (syn. mucormycoses) are rather rare but life-threatening diseases which often take a peracute course. Particularly endangered are diabetics and patients suffering from siderophilia. Zygomycosis is regularly complicated by thrombosis and subsequent necrosis. Usually it evolves from sinusitis in a rhinocerebral form. With the use of a clinical isolate (Rhizopus microsporus) and sera of the same female survivor, we investigated possible sources of the typical blood clotting. The results suggest that coagulation is probably initiated in a bimodal manner by an extracellular serine proteinase of the fungus and by elastase from the patients' leukocytes. The former causes a partial hydrolysis of fibrinogen, while the latter activates coagulation factor XIII (fibrin stabilizing factor). Both proteinases were present in the patient at the site of infection, and in vitro they jointly bring about regular clotting of fibrinogen
Characterization of an extracellular subtilisin protease ofRhizopus microsporusand evidence for its expression during invasive rhinoorbital mycosis
No full textAn endoprotease Arp (alkaline Rhizopus protease) was identified and purified to virtual homogeneity from the culture supernatant of an isolate of Rhizopus microsporus var. rhizopodiformis recovered from a non-fatal case of rhinoorbital mucormycosis. N-terminal sequencing of the mature native enzyme was obtained for the first 20 amino acids and revealed high homology to serine proteases of the subtilisin subfamily. Arp migrated in SDS-PAGE with an estimated molecular mass of 33 kDa and had a pI determined to be at pH 8.8. Arp is proteolytically active against various substrates, including elastin, over a broad pH range between 6 and 12 with an optimum at pH 10.5. After invasive mucormycosis, specific antibodies against Arp were detected in stored serum samples taken from the patient from whom the R. microsporus strain of this study had been isolated. Furthermore, in search of factors involved in thrombosis as a typical complication of mucormycosis, a procoagulatory effect of the enzyme has recently been shown. Altogether, these data substantiate the expression of Arp during human rhinoorbital mucormycosis and suggest a role of the enzyme in pathogenesis
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