Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0085437 (bacterial meningitis)
 4,038 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The CD14 antigen, an important cell surface molecule of monocytic cells, is involved in cellular activation: it binds lipopolysaccharide and other cellular lipid structures. Brain macrophages play a pivotal role during inflammatory reactions of the CNS parenchyma, ventricles and meninges. A soluble form of CD14 (sCD14) was measured in paired cerebrospinal fluid (CSF) and serum samples from 91 patients with different neurological diseases. Mean levels of circulating sCD14 in CSF in a control group of 22 patients with neurologic complaints but no neurological deficit on clinical examination were 0.19 +/- 0.06 (mean +/- SD) mg/l. The CSF/blood ratios of sCD14 was 49 +/- 16 x 10(-3), while those of albumin were 4.4 +/- 1.4 x 10(-3). These extremely high CSF/blood ratios of the sCD14 molecule compared to albumin indicate a local cerebral production. No significant changes in CSF sCD14 levels were found in patients with non-inflammatory neurological diseases (NID). In contrast, CSF sCD14 levels were markedly elevated during acute meningitis, but there was no direct correlation between sCD14 and monocyte count in the CSF. Thus, sCD14 could not originate in the CSF compartment from monocytes alone. The highest values for sCD14 were found in CSF during infections with various pathogens such as Staphylococcus aureus or Listeria monocytogenes. While sCD14 serum levels dramatically increased during acute bacterial meningitis, sCD14 ratios did not correlate with albumin ratios during the course of disease. Therefore, increased CSF sCD14 may originate from cerebral production by activated or infiltrated macrophages rather than passive diffusion from the blood, while elevated sCD14 serum levels resulted from enhanced local production. Increased CSF and serum sCD14 values were also observed in meningitis caused by viral infection. As in bacterial meningitis, sCD14 in CSF specimens did not correlate with the function of the blood/CSF barrier. Repeated lumbar punctures revealed a normalization of CSF sCD14 levels during clinical recovery. These results provide the first evidence for local production of sCD14 within the CNS. Our findings further indicate that sCD14 in CSF is a reliable marker for activation of macrophages within the CNS during inflammatory processes.
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PMID:Cerebrospinal fluid levels of soluble CD14 in inflammatory and non-inflammatory diseases of the CNS: upregulation during bacterial infections and viral meningitis. 1058 Jul 99

Forty-four patients scheduled for lumbar puncture (LP) were recruited to determine the level of penetration of orally administered rufloxacin into cerebrospinal fluid (CSF). The patients were divided into three clinical groups: those with normal CSF (groups A(1d) and A(7d)), those with aseptic meningitis (group B), and those with bacterial meningitis (group C). Members of group A(1d) received a single 400-mg rufloxacin dose, while group A(7d), B, and C constituents had a multiple-dose regimen (one 400-mg dose, followed by one 200-mg dose daily for 6 days). LP was performed on group A(1d) members 5 h after they had received treatment, while for group A(7d) it was undertaken 5 h after administration of the last dose. For group B, LP was performed 5 h after the first and the last doses, whereas for group C it was undertaken after the first, fourth, and last doses. Concentrations of rufloxacin in simultaneously collected CSF and plasma samples were determined. Mean CSF/plasma rufloxacin concentration ratios ranged from 0.57 to 0.84, depending on the study group. A higher, but not statistically significant, degree of penetration into CSF was observed in patients with bacterial meningitis than in those with normal CSF or aseptic meningitis. These data indicate that rufloxacin diffuses efficiently into the CSF of patients with either inflamed or uninflamed meninges.
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PMID:Penetration of rufloxacin into the cerebrospinal fluid in patients with inflamed and uninflamed meninges. 1060 26

Permanent neurologic disabilities are seen in up to a quarter of survivors of bacterial meningitis despite major improvements in therapy. Experimental studies have demonstrated that most of the pathology in meningitis is mediated by inflammatory cytokines such as tumor necrosis factor (TNF) and interleukin-1 (IL-1), which are produced by host cells in response to bacterial invasion of the meninges. Dexamethasone has been used in a number of clinical trials to moderate the host response and to improve neurologic outcome of meningitis. Results of six randomized, placebo controlled trials are summarized in this review. Dexamethasone treatment did not lower mortality. Only a moderate, but not a significant reduction in the neurologic and audiologic sequelae was seen in dexamethasone recipients when Haemophilus influenzae type b (Hib) was the causative agent of meningitis. Following routine use of Hib vaccine, meningitis caused by this agent has virtually disappeared in the USA. Hence, findings from these trials may no longer be applicable in countries with high rates of immunization against Hib. Presently, there is little or no evidence showing a benefit of dexamethasone therapy in meningitis caused by S. pneumoniae or N. meningitidis. Global emergence of penicillin and cephalosporin resistant S. pneumoniae has raised new concerns about the use of dexamethasone in pneumococcal meningitis. Since dexamethasone significantly decreases the penetration and concentration of vancomycin and ceftriaxone in the CSF and delays CSF sterilization, adjunctive dexamethasone therapy may increase the risk of treatment failure in meningitis caused by antibiotic resistant pneumococci. An antibiotic combination should be used in the treatment of meningitis caused by antibiotic resistant pneumococci, particularly if dexamethasone is also being administered concurrently.
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PMID:Dexamethasone in bacterial meningitis: to use or not to use? 1083 26

The interaction of Neisseria meningitidis with the meninges that surround and protect the brain is a pivotal event in the progression of bacterial meningitis. Two models of the human meninges were established in vitro, using (i) sections of fresh human brain and (ii) cultures of viable cells grown from human meningiomas. Neisseria meningitidis showed a specific predilection for binding to the leptomeninges and meningeal blood vessels in human brain and not to the cerebral cortex. There was a close correlation between the adherence of different Neisseria species to leptomeninges and cultured cells. The major ligand that mediated adherence was the pilus, and pilin variation modulated the interactions. The presence of Opa protein increased the association of Cap+ meningococci that expressed low-adhesive pili, but did not influence the association of high-adhesive pili. In contrast, Opc did not influence the adherence of Cap+ meningococci, whereas loss of capsule was associated with a more intimate interaction between the bacteria and the meningioma cell that was not apparent with Cap+ meningococci. There was no evidence of internalization of meningococci by meningioma cells in vitro, an observation that is consistent with the barrier properties of the leptomeninges to N. meningitidis observed in vivo.
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PMID:Interactions of Neisseria meningitidis with cells of the human meninges. 1084 70

To evaluate the spectrum and regulation of matrix metalloproteinases (MMPs) in bacterial meningitis (BM), concentrations of MMP-2, MMP-3, MMP-8, and MMP-9 and endogenous inhibitors of metalloproteinases (TIMP-1 and TIMP-2) were measured in the cerebrospinal fluid (CSF) of 27 children with BM. MMP-8 and MMP-9 were detected in 91% and 97%, respectively, of CSF specimens from patients but were not detected in control patients. CSF levels of MMP-9 were higher (P<.05) in 5 patients who developed hearing impairment or secondary epilepsy than in those who recovered without neurological deficits. Levels of MMP-9 correlated with concentrations of TIMP-1 (P<.001) and tumor necrosis factor-alpha (P=.03). Repeated lumbar punctures showed that levels of MMP-8 and MMP-9 were regulated independently and did not correlate with the CSF cell count. Therefore, MMPs may derive not only from granulocytes infiltrating the CSF space but also from parenchymal cells of the meninges and brain. High concentrations of MMP-9 are a risk factor for the development of postmeningitidal neurological sequelae.
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PMID:Matrix metalloproteinase (MMP)-8 and MMP-9 in cerebrospinal fluid during bacterial meningitis: association with blood-brain barrier damage and neurological sequelae. 1091 1

Effective laboratory animal models of bacterial meningitis are needed to unravel the pathophysiology of this disease. Previous models have failed to simulate human meningitis by using a directly intracerebral route of infection. Hyaluronidase is a virulence factor of Streptococcus pneumoniae. In this study, a novel model of murine meningitis is described. Intranasal administration of S. pneumoniae with hyaluronidase induced meningitis in 50% of inoculated mice, as defined by a positive cerebrospinal fluid (CSF) culture and an inflammatory infiltrate in the meninges. None of the mice inoculated without hyaluronidase developed meningitis. Hyaluronidase was found to facilitate pneumococcal invasion of the bloodstream after colonization of the upper respiratory tract. Meningitis was characterized by pleocytosis of CSF and the induction of proinflammatory cytokines and CXC chemokines in brain tissue. These results indicate that this murine model mimics important features of human disease and allow for the use of this model for studying issues related to the pathophysiology and the treatment of pneumococcal meningitis.
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PMID:Experimental pneumococcal meningitis in mice: a model of intranasal infection. 1123 45

Headache as a cardinal symptom of acute meningitis reflects activation of trigeminal afferents from the meninges. With their perivascular endings, these fibers form the so-called trigeminovascular system (TVS), which releases proinflammatory neuropeptides upon nociceptive stimulation. In the present article, we review a role of the TVS in enhancing the early inflammatory response of bacterial meningitis. Furthermore, we discuss inhibition of neuropeptide release from the TVS using 5HT(1B/D) agonists as a potential new anti-inflammatory treatment strategy for early bacterial meningitis.
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PMID:The trigeminovascular system in bacterial meningitis. 1130 94

The purpose of this article is to describe, with 5 clinical cases, the physiological communications between the inner ear and the subarachnoid spaces (SAS) and present the imaging features with regard to. Therefore we briefly illustrate abnormal communications between SAS and perilymphatic fluids in certain cochlear and internal acoustic meatus (IAM) malformations and their consequences. Imaging features may depict diffusion pathway of bacterial meningitis to membranous labyrinth via the cochlear aqueduct or via the IAM. Rarely, in some patients referred for cochleovestibular symptoms, imaging features may display skull base tumors involving the area of cochlear or vestibular aqueduct aperture. Therefore, in patients referred for cochleovestibular symptoms, MR and CT study should carefully scrutinise not only the IAM but also the aperture of the cochlear and the vestibular aqueducts and the cerebellopontine meninges.
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PMID:[Inner ear and subarachnoid spaces: relations and diseases]. 1143 91

Due to normal growth and development, hospitalised paediatric patients with infection require unique consideration of immune function and drug disposition. Specifically, antibacterial and antifungal pharmacokinetics are influenced by volume of distribution, drug binding and elimination, which are a reflection of changing extracellular fluid volume, quantity and quality of plasma proteins, and renal and hepatic function. However, there is a paucity of data in paediatric patients addressing these issues and many empiric treatment practices are based on adult data. The penicillins and cephalosporins continue to be a mainstay of therapy because of their broad spectrum of activity, clinical efficacy and favourable tolerability profile. These antibacterials rapidly reach peak serum concentrations and readily diffuse into body tissues. Good penetration into the cerebrospinal fluid (CSF) has made the third-generation cephalosporins the agents of choice for the treatment of bacterial meningitis. These drugs are excreted primarily by the kidney. The carbapenems are broad-spectrum beta-lactam antibacterials which can potentially replace combination regimens. Vancomycin is a glycopeptide antibacterial with gram-positive activity useful for the treatment of resistant infections, or for those patients allergic to penicillins and cephalosporins. Volume of distribution is affected by age, gender, and bodyweight. It diffuses well across serous membranes and inflamed meninges. Vancomycin is excreted by the kidneys and is not removed by dialysis. The aminoglycosides continue to serve a useful role in the treatment of gram-negative, enterococcal and mycobacterial infections. Their volume of distribution approximates extracellular space. These drugs are also excreted renally and are removed by haemodialysis. Passage across the blood-brain barrier is poor, even in the face of meningeal inflammation. Low pH found in abscess conditions impairs function. Toxicity needs to be considered. Macrolide antibacterials are frequently used in the treatment of respiratory infections. Parenteral erythromycin can cause phlebitis, which limits its use. Parenteral azithromycin is better tolerated but paediatric pharmacokinetic data are lacking. Clindamycin is frequently used when anaerobic infections are suspected. Good oral absorption makes it a good choice for step-down therapy in intra-abdominal and skeletal infections. The use of quinolones in paediatrics has been restricted and most information available is in cystic fibrosis patients. High oral bioavailability is also important for step-down therapy. Amphotericin B has been the cornerstone of antifungal treatment in hospitalised patients. Its metabolism is poorly understood. The half-life increases with time and can be as long as 15 days after prolonged therapy. Oral absorption is poor. The azole antifungals are being used increasingly. Fluconazole is well tolerated, with high bioavailability and good penetration into the CSF. Itraconazole has greater activity against aspergillus, blastomycosis, histoplasmosis and sporotrichosis, although it's pharmacological and toxicity profiles are not as favourable.
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PMID:Commonly used antibacterial and antifungal agents for hospitalised paediatric patients: implications for therapy with an emphasis on clinical pharmacokinetics. 1170 24

Myeloid (CD11c+) dendritic cells (DC) are present in cerebrospinal fluid (CSF), as well as in the meninges and choroid plexus. Functional studies of these DC are hindered or impossible. To obviate this problem, we investigated the effects of CSF supernatants from patients with non-inflammatory neurological diseases (NIND), multiple sclerosis (MS), bacterial meningitis (BM) and Lyme meningoencephalitis (LM) on immature monocyte-derived DC (moDC) from healthy donors. CSF supernatants caused maturation of moDC (MS > LM > NIND > BM), as reflected by a decrease in CD1a, and an increase in HLA-DR, CD80 and CD86 expression. The maturation effect of MS CSF and LM CSF could be blocked by anti-TNF-alpha MoAb or recombinant human IL-10. moDC cultured with BM CSF either remained immature or turned into CD14+ macrophage-like cells and were relatively inefficient at inducing T cell responses in vitro. In contrast, moDC cultured with LM CSF induced strong Th1 responses. Both BM CSF and LM CSF contained IFN-gamma, a cytokine that augments IL-12 production by moDC and hence should confer an ability to induce a Th1 response. However, BM CSF also contained high levels of IL-10, which could antagonize the effects of IFN-gamma on moDC. moDC cultured with MS CSF induced a higher production of IFN-gamma from T cells compared to moDC cultured with NIND CSF or BM CSF. In summary, soluble factors present in the CSF may influence the phenotype and functions of meningeal, choroid plexus and CSF DC which, in turn, may have an impact on the character of intrathecal T cell responses.
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PMID:Cerebrospinal fluid affects phenotype and functions of myeloid dendritic cells. 1198 31


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