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

Bacterial meningitis was found in 12 patients with nasopharyngeal carcinoma, accounting for 0.65% of the 1850 patients with the tumour diagnosed between 1981 and 1994 in our hospital. In 11 patients, the time-lag between diagnosis of cancer and the appearance of infection ranged from 9 months to 11 years (mean 57 months) whereas in one patient it was only 5 days. Three patients developed mixed bacterial meningitis. Cerebrospinal fluid culture for bacteria was positive in six patients. Three patients (25%) were bacteraemic. Gram-negative bacilli, especially Pseudomonas aeruginosa, were the most common pathogens. Age, sex and histopathology were not risk factors for infection. Conditions predisposing to meningitis included intracranial invasion of the tumor, neutropenia, otitis media, and neurosurgical procedures. All but two patients had intracranial tumour invasion and erosion of the base of the skull. Local spread of micro-organism to the meninges was more important than haematogenous spread. The overall mortality in our patients was 66.7%, much higher than in patients without cancer.
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PMID:Bacterial meningitis in patients with nasopharyngeal carcinoma. 873 Mar 45

Cefepime and cefpirome are new beta-lactamase resistant parenteral cephalosporin derivatives whose spectrum of activity makes them suitable for use in the treatment of severe infections such as bacterial meningitis. However, the published information on the penetration of these new agents into human CSF and on their use in the treatment of bacterial meningitis are really scarce. Experimental studies have shown that cefepime and cefpirome penetrated remarkably well into the CSF of animals infected with Streptococcus pneumoniae, Streptococcus agalactiae, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae type b or Pseudomonas aeruginosa. The mean changes in bacterial colony count in CSF after cefpirome or cefepime administration express the antibacterial activity of these drugs. Studies in patients show that cefepime and cefpirome crossed the blood-brain barrier and reached concentrations in the CSF that are bactericidal against most potential pathogens. Higher levels are likely to be achieved with multiple dosing and in the presence of inflamed meninges. No study has been performed to investigate the efficacy of cefpirome in the treatment of bacterial meningitis. Cefepime was as effective and safe as cefotaxime for treatment of patients with bacterial meningitis as shown in the only clinical trial.
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PMID:Diffusion of 3-quaternary ammonium cephem antibiotics into cerebrospinal fluid of patients with bacterial meningitis. 873 50

It is well established that sensorineural hearing loss (SNHL) is an important sequela of acute bacterial meningitis. Previous human temporal bone histopathologic studies have suggested that such hearing loss is due to labyrinthitis. This study involved a detailed and systematic evaluation of the auditory and vestibular end-organs in 41 human temporal bones from patients with acute bacterial meningitis, aimed at describing the spectrum of histopathologic changes within the labyrinth, ascertaining likely routes for spread of infection from the meninges to the inner ear, and comparing the data from humans with those described in a rabbit model of meningogenic labyrinthitis. Our study revealed the following: (a) Suppurative labyrinthitis occurred in 20 (49%) bones. Of these 20 bones, the cochlea was affected in all, whereas the vestibular organs were involved in 10. Eosinophilic staining of inner ear fluids without the presence of inflammatory cells (so-called "serous" labyrinthitis) occurred in 14 of the remaining 21 bones. This staining occurred primarily within the vestibular system. Its significance and pathogenesis remains unknown; (b) Sensory and neural structures of the inner ear appeared intact in the majority of specimens, including bones with suppurative labyrinthitis and those with eosinophilic staining of inner ear fluids. This finding raises the possibility of preventing or reversing SNHL by therapeutic intervention. Spiral ganglion cells were severely degenerated in 12% of bones, indicating a retrocochlear site of hearing loss in addition to the cochlea. This subset of patients may perform poorly after cochlear implantation; (c) It has been traditionally assumed that irreversible and permanent SNHL is caused by suppurative labyrinthitis, whereas reversible SNHL is caused by serous labyrinthitis. Our findings question the validity of these assumptions; (d) The data were consistent with the hypothesis that both the cochlear modiolus and cochlear aqueduct can serve as potential pathways for spread of infection from the meninges to the inner ear; (e) There were many similarities in the histopathology of the inner ear in humans when compared with the rabbit model of meningogenic labyrinthitis. A notable difference was that the cochlear aqueduct appeared to be the sole pathway for spread of infection in the rabbit, whereas in the human, both the modiolus and aqueduct were possible pathways.
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PMID:A human temporal bone study of acute bacterial meningogenic labyrinthitis. 881 13

We investigated whether trigeminal nerve fibers contribute to enhanced regional cerebral blood flow (rCBF) in a rat model of experimental bacterial meningitis. rCBF was measured continuously for 6 h by laser Doppler flowmetry through thinned bone over the frontal cortex. Meningitis was induced with pneumococcal cell wall components and confirmed by a significant increase of (a) leukocytes within the cerebrospinal fluid, (b) brain water content, (c) intracranial pressure and (d) rCBF. The increase of rCBF was significantly attenuated (p < 0.05) at 3, 4, 5, and 6 h in animals after a chronic (200 +/- 21% versus 138 +/- 13% at 6 h on the intact and denervated sides, respectively) but not after an acute section of the nasociliary branch of the trigeminal nerve. We conclude that elevations in blood flow during the early phase of bacterial meningitis are mediated in part by the trigeminal nerve, probably by local perivascular release of neuropeptides from afferent axons innervating the meninges.
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PMID:The trigeminal nerve and augmentation of regional cerebral blood flow during experimental bacterial meningitis. 889 7

The anaphylatoxin C5a has been implicated in the pathogenesis of bacterial meningitis as a potent mediator of inflammation in the subarachnoid space. We investigated the expression of the receptor for C5a (C5aR) in brains of mice with experimental Listeria monocytogenes (LM) meningoencephalitis. In the course of the disease, infiltrating cells in the meninges and the ventricles were found to express C5aR mRNA and protein. In the brain parenchyma, very low constitutive C5aR expression was seen on pyramidal neurons and Purkinje cells. However, in LM-infected mice, a dramatic increase in C5aR expression occurred on neurons starting 6 h after infection and was maximal between 24 and 36 h. TNF-alpha was identified as an essential mediator of neuronal C5aR expression, since mice lacking the genes for TNF and lymphotoxin-alpha (TNF/lymphotoxin-alpha -/- mice) showed significantly attenuated C5aR expression after LM infection. Furthermore, i.p. injection of recombinant TNF-alpha induced enhanced C5aR expression in the brains of TNF/lymphotoxin-alpha -/- mice and in normal animals even in the absence of a bacterial infection. We also assessed the levels of anaphylatoxin C5a in the cerebrospinal fluid of patients with infectious meningitis. C5a was detected in all patients with bacterial meningitis (n = 9), in 6 of 18 patients with aseptic meningitis, and in 1 of 66 control patients. The finding of TNF-alpha-mediated C5aR expression on neurons in experimental Listeria meningitis and the detection of the ligand, C5a, in the cerebrospinal fluid of human patients with infectious meningitis present new directions in the investigation of the pathophysiologic sequelae leading to secondary brain damage.
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PMID:TNF-alpha-mediated expression of the receptor for anaphylatoxin C5a on neurons in experimental Listeria meningoencephalitis. 921 5

The choice of an antibiotic for the treatment of a serious paediatric infection is generally a difficult problem. The arrival of Carbapenem resulted an important advance in the field of medicine due to its broad-spectrum, low incidence of resistances and good safety profile. Among Carbapenems, Meropenem introduction represents a progress because of its pharmacokinetics characteristics and blood-brain barrier penetration. Meropenem dosage depends on the patient weight, and the way of administration is potentially easier. Meropenem has been compared with the most used paediatric antimicrobial in controlled and randomised clinical trials, showing a high efficacy in the treatment of several infections (respiratory, urinary, intraabdominal, dermatological, septicemia) and in neutropenic and cystic fibrosis patients aged between one month and twelve years old. Meropenem is specially useful in the bacterial meningitis treatment because it penetrates into the cerebrospinal fluid of patients with inflamed meninges and reaches therapeutic concentrations, and because appearance of seizures is low. Adverse reactions produced by Meropenem show a poor incidence and its severity is usually mild. With regard to this characteristics, it can be concluded that Meropenem is an antimicrobial which efficacy and safety profiles guarantee its use in the treatment of severe paediatric infections.
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PMID:[Clinical pharmacology and indications of meropenem in severe pediatric infection]. 941 68

Although meninges represent a major site of biosynthesis, beta-trace protein (beta-trace) has not been studied in the cerebrospinal fluid (CSF) of meningitis patients. We measured beta-trace in lumbar CSF of normal controls (n = 27) and in patients with various neurological diseases (n = 92) by an immunonephelometric assay. The mean concentration of beta-trace in CSF of control patients was 16.6+/-3.6 mg/l. In bacterial meningitis (n = 41), CSF beta-trace was significantly decreased (8.7+/-3.9 mg/l; P< 0.001), whereas in spinal canal stenosis it was elevated (29.2+/-10.3 mg/l; P= 0.002). In viral meningoencephalitis (n = 12), beta-trace CSF concentrations were normal. Beta-trace concentrations remained below the normal range even after curing of bacterial meningitis, and normalisation of CSF leucocytes and blood-CSF barrier function. Beta-trace may be a useful tool for studying the pathophysiology of bacterial meningitis.
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PMID:Beta-trace protein concentration in cerebrospinal fluid is decreased in patients with bacterial meningitis. 950 92

Cancer cells as well as bacteria metastasize to the subarachnoidal space (SAS) causing meningitis. Primary brain tumors, although not forming distant metastases, disseminate via the cerebrospinal fluid and occupy the meninges. The multistep process of cancer or bacterial dissemination is regulated through molecular crosstalk between invaders and host cells. Such crosstalks establish invasion-promoter and invasion-suppressor complexes. In carcinomatous and bacterial meningitis, the participation of host cells is prominent since leukocytes and inflammatory cytokines are the major determinants of malignancy. We propose a model in which bacterial breakdown products activate endothelial cells, a process leading to leukocyte extravasation. This initiates a cascade of inflammatory processes opening up the blood cerebrospinal fluid barrier and producing access for new invaders.
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PMID:Cellular and molecular mechanisms of metastasis as applied to carcinomatous meningitis. 969 58

A leading cause of morbidity from bacterial meningitis is an irreversible, usually profound sensorineural hearing loss, with an incidence as high as 30% in some studies. Bacterial meningitis remains the most common cause of acquired postnatal sensorineural deafness. Although several clinical studies have examined the long-term outcome of hearing in meningitis, few studies have examined the time course of hearing loss during the acute course of the disease. We have developed an animal model of meningogenic hearing loss in the rat and have plotted the time course of that hearing loss. Serial auditory brain stem responses (ABRs) were measured in rats inoculated in the cisterna magna (subarachnoid space) with Streptococcus pneumoniae (10(5) to 10(7) colony-forming units). All rats injected developed meningitis as evidenced by increased cerebrospinal fluid (CSF) white cell counts and positive CSF cultures. Serial ABR measurements taken 6, 12, 15, 18, 21, and 24 hours after inoculation demonstrated significant threshold shifts and eventual loss of the ABR waveform as compared with measurements in control rats injected with sterile culture medium. Hearing loss began approximately 12 to 15 hours after inoculation and progressed to complete loss by 24 hours (17 of 18 animals). No correlation was found between the magnitude of hearing loss and CSF white cell count or bacterial titer. Temporal bone histology of rats with meningitis shows a dense inflammatory cell infiltrate throughout the subarachnoid space. Labyrinthine inflammatory cells were confined to the scala tympani. The cochlear aqueduct is the proposed route of infection from the meninges to the labyrinth (scala tympani). Endolymphatic hydrops was also noted throughout the cochlea. These experiments both establish a reproducible animal model of meningogenic hearing loss and support the hypothesis that this hearing loss is progressive rather than abrupt in onset and is related to the duration of untreated infection. CSF inflammatory cells appear to enter the cochlea through the cochlear aqueduct. This reliable animal model will enable future studies directed toward further understanding the pathogenesis and pathophysiology of this hearing loss.
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PMID:Time course of hearing loss in an animal model of pneumococcal meningitis. 1022 85

Leukocyte infiltration of the CSF and brain parenchyma and other parameters of inflammation during pneumococcal meningitis were investigated after reduction of meningeal macrophages in rabbits by intracisternal injection of dichloromethylene-diphosphonate (Cl2MDP)-containing liposomes. Macrophages in the meninges were reduced, in median, by approximately 77% after three intrathecal injections of 100 microl of liposomes containing Cl2MDP at 12 h intervals. Production of the cytokines interleukin-1 and tumor necrosis factor-alpha as well as infiltration of the CSF and nervous tissue by leukocytes was not significantly altered in infected animals after treatment with Cl2MDP-containing liposomes. The median CSF concentration of neuron specific enolase (NSE) as a parameter of neuronal damage was higher in infected Cl2MDP-treated animals (median [median (25th/75th percentiles): 44.7 (33.2/54.3) microg/l vs. 13.9 (10.4/23.9) microg/l; P = 0.01]). Therefore, the reduction of meningeal macrophages does not appear to attenuate inflammation in the subarachnoid space in experimental pneumococcal meningitis. Meningeal macrophages seem, however, to be important for the protection of neuronal tissue in bacterial meningitis.
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PMID:Reduction of meningeal macrophages does not decrease migration of granulocytes into the CSF and brain parenchyma in experimental pneumococcal meningitis. 1050 76


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