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Query: UMLS:C0085437 (bacterial meningitis)
 4,038 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiac hemodynamics were assessed by right and left heart catheterizations in nine patients on hemodialysis. Results showed increased stroke work index and left ventricular work indices. Left ventricular end-diastolic pressure was elevated in all patients (markedly so in five) and did not fall with occlusion of arteriovenous communications. Cardiac output was significantly elevated, but fell to normal postocclusion. Myocardial oxygen consumption, indirectly assessed by tension time and pressure rate indices, appeared increased. Six patients died: four from complications attributed to myocardial failure without infarction, one from transplant-related complications, and one from bacterial meningitis. Five had increased cardiac weights at autopsy, but none showed infarction. This study suggests that increased cardiac work is present in chronic renal failure. Myocardial mass increases result in increased myocardial oxygen demand; however, the increased oxygen requirements may not be met because of reduced erythrocyte mass. Persistance of pressure-volume overload and severe anemia are conducive to myocardial failure.
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PMID:Cardiac work demands and left ventricular function in end-stage renal disease. 13 18

For the past several years immunologists have been fascinated by a series of experiments showing that transforming growth factor beta (TGF beta) suppresses T- and B-lymphocyte growth as well as IgM and IgG production by B cells. Moreover, while exerting chemotactic activity on monocytes and inducing expression of interleukin-1 and interleukin-6 by these cells, TGF beta interferes with bacterially induced tumor necrosis factor alpha production, oxygen radical formation and the adhesiveness of granulocytes to endothelial cells. These mechanisms may provide the basis for the effect of TGF beta to prevent the microvascular changes associated with brain edema formation in bacterial meningitis. Given the potential of lymphocytes as well as macrophages to produce TGF beta 1, this cytokine may exert negative feedback signals on the immune response, provided the cytokine is processed from its latent form to the bioactive homodimer. Potent effects of TGF beta have been observed in experimental animals including the inhibition of the generation of virus-specific cytotoxic T cells and antiviral antibodies as well as the diminution of cellular infiltrates with decreased major histocompatibility complex class-II expression and CD8+ T cells in the tissue of virally infected animals. TGF beta may also be of importance in tumor immunology. By the production of bioactive TGF beta as detected in glioblastoma and acute T-cell leukemia, tumor cells may induce an immunodeficiency state and escape immune surveillance. In inflammation, monitoring of TGF beta in the tissue will bring light on the immune regulation in acute and chronic inflammatory diseases.
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PMID:Modulation of the immune response by transforming growth factor beta. 148 57

This report emphasizes new clinical information about bacterial meningitis in infants and children. Important elements of diagnosis include examination for the presence of shock and increased intracranial pressure. In such cases, initial treatment should focus on appropriate fluid therapy, administration of oxygen, reduction of intracranial pressure and use of corticosteroids. Currently, antibiotics of choice include ampicillin plus either cefotaxime or ceftriaxone in young infants, and one of these cephalosporins in older patients (beyond 3 months of age). Shorter durations of therapy (5 to 7 days for meningococcus, 7 days for haemophilus and 7-10 days for pneumococcus) are now commonly employed. In many centers, dexamethasone is started before the first dose of antibiotic and continued for 4 days to reduce neurologic and audiologic sequelae. Future trends will include studies of endotoxin neutralizers and non-steroidal anti-inflammatory drugs to reduce further tissue injury in meningitis. Prevention of meningitis is the ultimate goal. Since Haemophilus influenzae vaccination can now begin at 2 months, this approach may bring important results soon.
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PMID:Bacterial meningitis--an update. 176 75

The purpose of this study was to identify mediators of brain oedema formation in experimental pneumococcal meningitis. In a rat model of pneumococcal meningitis brain water content was significantly elevated 6 hours post infection (79.69% +/- 0.24 compared to 78.94% +/- 0.16 in the control group, mean +/- SEM, p less than 0.05). Brain oedema formation was completely blocked by superoxide dismutase (132,000 U/kg i.v. per 6 hours: n = 6), pretreatment with dexamethasone (3 mg/kg i.p., n = 3), or administration of dexamethasone at two hours after pneumococcal injection (n = 5). Pretreatment with indomethacin (10 mg/kg i.v., n = 5) attenuated the brain oedema formation. These findings suggest that oxygen derived free radicals act as mediators of brain oedema formation during the early phase of experimental bacterial meningitis. Cyclooxygenase metabolites may provide one possible source for the generation of oxygen derived free radicals in bacterial meningitis.
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PMID:Superoxide dismutase inhibits brain oedema formation in experimental pneumococcal meningitis. 208 45

Rabbits models of bacterial meningitis have contributed substantially to our understanding of the disease, although the technical characteristics of these models only allow the study of specific aspects of the disease. Bacterial multiplication in the subarachnoidal space is not substantially influenced by host defense mechanisms, mainly because of the lack of sufficient amounts of specific antibodies and functional complement in infected CSF. The multiplying bacteria induce profound changes in the blood-brain barrier, an influx of serum proteins into the CSF and the invasion of polymorphonuclear leukocytes at the site of the infection. The presence of polymorphonuclear leukocytes in CSF not only appears to be of limited value in combating the infection, but also seems to produce deleterious effects on the central nervous system. Components of the leukocytes, such as unsaturated fatty acids, arachidonic metabolites and free oxygen radicals, may contribute to the profound hydrodynamic, structural and metabolic changes that are currently under study in experimental models of the disease. A better understanding of the pathophysiology of bacterial meningitis may allow us to design more effective therapeutic strategies and improve the outcome of this disease.
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PMID:Pathogenesis of bacterial meningitis: contributions by experimental models in rabbits. 639 52

Morbidity and mortality associated with bacterial meningitis remain high, although antibiotic therapy has improved during recent decades. The major intracranial complications of bacterial meningitis are cerebrovascular arterial and venous involvement, brain edema, and hydrocephalus with a subsequent increase of intracranial pressure. Experiments in animal models and cell culture systems have focused on the pathogenesis and pathophysiology of bacterial meningitis in an attempt to identify the bacterial and/or host factors responsible for brain injury during the course of infection. An international workshop entitled "Bacterial Meningitis: Mechanisms of Brain Injury" was organized by the Department of Neurology at the University of Munich and was held in Eibsee, Germany, in June 1993. This conference provided a forum for the exchange of current information on bacterial meningitis, including data on the clinical spectrum of complications, the associated morphological alterations, the role of soluble inflammatory mediators (in particular cytokines) and of leukocyte-endothelial cell interactions in tissue injury, and the molecular mechanisms of neuronal injury, with potential mediators such as reactive oxygen species, reactive nitrogen species, and excitatory amino acids. It is hoped that a better understanding of the pathophysiological events that take place during bacterial meningitis will lead to the development of new therapeutic regimens.
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PMID:Mechanisms of brain injury in bacterial meningitis: workshop summary. 781 66

Among the important pathophysiologic alterations in the brain in bacterial meningitis are abnormalities of cerebral circulation and metabolism; however, the precise mechanisms by which these disturbances occur are not completely delineated. It has been recently recognized that cytokines are produced by tissues in the central nervous system in meningitis and play a critical role in the host inflammatory response. Because these mediators are involved in circulatory and metabolic disturbances in other tissues in sepsis, we investigated the role of tumor necrosis factor-alpha in the central nervous system in a rabbit model. We found that injection of recombinant human TNF into the cisterna magna in the rabbit led to an acute reduction in cerebral oxygen uptake and a more prolonged reduction in cerebral blood flow. This was accompanied by an increase in intracranial pressure and an increase in cerebrospinal fluid lactate. Reduction in oxygen uptake and increases in intracranial pressure and CSF lactate were blocked by pretreatment with L-NAME, an inhibitor of nitric oxide synthase. Reduction in cerebral blood flow was not affected by L-NAME treatment and was due to increased cerebrovascular resistance and reduced oxygen demand. These results suggest that TNF may be a critical mediator of changes in cerebral circulation and metabolism and that some of these changes occur via the nitric oxide pathway.
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PMID:Effect of recombinant human tumor necrosis factor-alpha on cerebral oxygen uptake, cerebrospinal fluid lactate, and cerebral blood flow in the rabbit: role of nitric oxide. 788 56

Polymorphonuclear leukocytes are armed with an impressive arsenal of bactericidal agents that allow these cells to play a vital role in host defense against invading pathogens. However, these same agents can produce extensive cellular damage in host tissues when leukocytes are activated during inflammatory conditions. Recognition of this fact, when coupled with the observation that leukocyte adhesion to post-capillary venules is a critical first step in the inflammatory process, has led to the development of the concept that inhibition of neutrophil-endothelial cell adhesion (NECA) may represent a novel therapeutic strategy for the prevention of leukocyte-dependent injury in inflammatory conditions. Indeed, pharmacological or immunologic inhibition of NECA reduces cellular injury, dysfunction, and necrosis induced by ischemia/reperfusion, circulatory shock and resuscitation, organ transplantation, cardiopulmonary bypass, frostbite, and thermal trauma. NECA also appears to play an important role in the pathobiology of airway inflammation and asthma, pulmonary oxygen toxicity, arthritis, bacterial meningitis, and cerebral malaria. The aim of this review is to summarize the evidence implicating NECA in the pathogenesis of these inflammatory conditions.
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PMID:Role of neutrophil-endothelial cell adhesion in inflammatory disorders. 819 53

The effect of experimental meningitis on regional cerebral blood flow (rCBF), cerebral metabolic rate for oxygen (CMRO2), and cerebrovascular responsiveness to CO2 was determined in pentobarbital-anesthetized rabbits. The animals were inoculated intracisternally with saline (control) or log-phase Haemophilus influenzae type b (Hib). Eighteen hours later rCBF was determined with radiolabeled microspheres at normocapnia, hypocapnia, and hypercapnia. Cerebrovascular responses to hypocapnia and hypercapnia were assessed by calculating the change in cerebrovascular resistance per millimeter mercury change in PaCO2. At all CO2 levels, meningitis (M) was associated with elevated CBF compared with control (C: 47.5 +/- 3.0, M: 60.9 +/- 4.5 ml.100 g-1.min-1 at normocapnia, P < 0.01). Regional differences were present. In forebrain, the hyperemia in meningitis was confined to the superficial cortical grey matter. When compared with control, meningitis was not associated with altered vasoreactivity during hypocapnia (C: -0.026 +/- 0.006, M: -0.026 +/- 0.008 mmHg.ml-1 x 100 g-1.min-1.mmHg PaCO2(-1)) or hypercapnia (C: -0.037 +/- 0.004, M: -0.026 +/- 0.008 mmHg.ml-1 x 100 g.min.mmHg PaCO2(-1)). CMRO2 in meningitis was not significantly different from control (C: 3.53 +/- 0.29, M: 3.51 +/- 0.22 ml O2.100 g-1.min-1). These findings indicate that cerebrovascular responsiveness to CO2 is preserved in experimental Hib meningitis. Furthermore, enhanced CBF together with unchanged CMRO2 indicates that "luxury" cerebral perfusion is present in this model of bacterial meningitis.
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PMID:Cerebrovascular responsiveness to CO2 in Haemophilus influenzae type b meningitis in rabbits. 820 76

Cytokines are involved in the host response to bacterial infections. In bacterial meningitis, intrathecal synthesis of TNF-alpha and IL-1 is likely to contribute to CNS injury by recruitment and activation of inflammatory cells with subsequent release of toxic factors, such as reactive oxygen intermediates and excitatory amino acids (glutamate), leading to neuronal cell death with neurologic sequelae. In rats with experimental meningitis, pretreatment with TGF-beta inhibits cerebrovascular changes and brain edema formation in the early, TNF-alpha-independent phase. Provided its local production in bacterial infection, TGF-beta may comprise a host factor interfering with immune pathologic events altering the integrity of the endothelial barrier.
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PMID:Immune-mediated injury in bacterial meningitis. 845 12


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