RESUMEN
Phagocytic cells contain NADPH oxidase that they use for host defense by catalyzing the production of superoxide. Bacterial lipopolysaccharide (LPS) has been found to stimulate NADPH oxidase in mobile and sessile macrophages and microglia. It also evokes fever in homeothermic animals and men, a reaction mediated by central nervous system (CNS) activities. The purpose of the present study was to determine whether reactive oxygen species are involved in LPS-induced fever. In rabbits we found that plasma hydroperoxide levels increased and catalase activity decreased 15 min after LPS injection and that fever started with a similar latency, while plasma levels of tumor necrosis factor-alpha (TNFalpha) increased 30 min after the injection. Treating rabbits with methylene blue or aspirin did not affect TNFalpha secretion but prevented the LPS-induced rise of hydroperoxides and the inactivation of catalase, abolishing fever. Incubation of human blood with nitroblue tetrazolium and LPS increased the number of formazan-positive neutrophils from 10 +/- 5 to 52 +/- 9%. Adding LPS to blood preincubated with either methylene blue, alpha-lipoic acid, or aspirin respectively decreased the number of formazan-positive neutrophils to 0.9 +/- 0.8, 0.8 +/- 0.9, or 2.0 +/- 0.9%, disclosing the antioxidant capacity of these drugs. Systemic application of 80 mg/kg alpha-lipoic acid elicited heat-loss reactions within 15 min and decreased core temperature by 2.2 +/- 0.3 degrees C within 2 h. Alpha-lipoic acid applied 45 min after LPS induced antipyresis within 15 min, and this antipyresis was associated with a decrease of elevated hydroperoxide levels and restoration of catalase activity. Our results show that fever is prevented when the production of reactive oxygen species is blocked and that an elevated body temperature returns to normal when oxygen radical production decreases. Estimation of plasma dihydrolipoic acid (DHLA) levels following injection of 80 mg/kg alpha-lipoic acid in afebrile and febrile rabbits revealed that this acid is converted into DHLA, which in afebrile rabbits increased the plasma DHLA concentration from 2.22 +/- 0.26 microg/ml to peak values of 8.60 +/- 2.28 microg/ml DHLA within 30 min and which in febrile rabbits increased it from 0.84 +/- 0.22 microg/ml to peak values of 3.90 +/- 0.94 microg/ml within 15 min. Methylene blue, aspirin, and alpha-lipoic acid, which all cross the blood-brain barrier, seem to act not only on peripheral tissues but also on the CNS. Brain structures that have been shown to sense oxidative stress are vicinal thiol groups attached to the NMDA subtype of glutamate receptor. Their reduction by thiol-reducing drugs like dithiothreitol or DHLA has been found to increase glutamate-mediated neuronal excitability, while the opposite effect has been observed after their oxidation. Because we found that systemic application of alpha-lipoic acid in the afebrile state elicits hypothermia and in the febrile state is antipyretic, we think this type of NMDA receptor is involved in thermoregulation and that oxidation of its thiol groups induces fever. It appears that temperature homeostasis can be maintained only if the redox homeostasis of the brain is guaranteed.
Asunto(s)
Aspirina/farmacología , Fiebre/prevención & control , Azul de Metileno/farmacología , Especies Reactivas de Oxígeno/metabolismo , Ácido Tióctico/análogos & derivados , Ácido Tióctico/farmacología , Animales , Antioxidantes/metabolismo , Infecciones Bacterianas/complicaciones , Infecciones Bacterianas/etiología , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Catalasa/sangre , Catalasa/líquido cefalorraquídeo , Endotoxinas/sangre , Endotoxinas/líquido cefalorraquídeo , Femenino , Fiebre/etiología , Fiebre/metabolismo , Formazáns/análisis , Formazáns/metabolismo , Peróxido de Hidrógeno/sangre , Peróxido de Hidrógeno/líquido cefalorraquídeo , Inyecciones Intravenosas , Lipopolisacáridos/administración & dosificación , Lipopolisacáridos/sangre , Lipopolisacáridos/líquido cefalorraquídeo , Perfusión , Conejos , Espacio Subaracnoideo/efectos de los fármacos , Espacio Subaracnoideo/metabolismo , Ácido Tióctico/metabolismo , Ácido Tióctico/farmacocinética , Factor de Necrosis Tumoral alfa/metabolismoAsunto(s)
Cefalosporinas/uso terapéutico , Endotoxinas/líquido cefalorraquídeo , Meningitis Bacterianas/tratamiento farmacológico , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa , Adulto , Cefalosporinas/efectos adversos , Líquido Cefalorraquídeo/microbiología , Endotoxinas/sangre , Resultado Fatal , Humanos , Japón , Masculino , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/crecimiento & desarrollo , Pseudomonas aeruginosa/metabolismo , CefozopránRESUMEN
Endotoxin levels were measured in the blood and cerebrospinal fluid (CSF) of control individuals and 2 groups of patients with African sleeping sickness. Endotoxin levels were markedly elevated in the blood (infected groups mean endotoxin values 40.2 pg/ml and 53.8 pg/ml, compared to control 11.6 pg/ml, P < 0.0001 for both increases) and CSF (infected groups mean endotoxin values 45.8 pg/ml and 50.1 pg/ml compared to control 6.3 pg/ml, P < 0.0001 for both increases) of the patients. The levels were reduced 6 weeks following different drug treatments in the 2 groups (blood levels to mean 33.8 pg/ml and 28.5 pg/ml; CSF levels to 37.4 pg/ml and 27.0 pg/ml). The blood endotoxin values correlated with the CSF values before treatment (r = 0.74 and 0.57 for the 2 groups; P < 0.0001 for both) and after treatment (r = 0.57 and 0.56 for the 2 groups; P < 0.0001 for both). It is concluded that raised endotoxin equilibrates in the blood and CSF compartments, and may contribute significantly to the pathology of sleeping sickness.
Asunto(s)
Endotoxinas/sangre , Endotoxinas/líquido cefalorraquídeo , Tripanosomiasis Africana/sangre , Tripanosomiasis Africana/líquido cefalorraquídeo , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Tripanosomiasis Africana/tratamiento farmacológicoRESUMEN
Using a new endotoxin-specific chromogneic limulus assay (Endoscopy test), endotoxin concentrations were measured in 93 specimens of cerebrospinal fluid (CSF) from 66 pediatric patients. Eighteen patients were diagnosed as having menigitios. Of these, 6 cases (group A) with gram-negative meningitis proven by culture had high CSF endotoxin concentrations of 115.3, (82-133) (median, range) pg/ml. Ten cases (group B) with gram-positive or aseptic meningitis had endotoxin concentrations of 2.15 (0.1-3.6) pg ml. Other 2 cases with bacterial meningitis (group C), in whom no pathogen was detected, had CSF endotoxin concentrations of more than 100 pg/ml. Four cases with encephalitis (group D) and 45 cases with non-meningitis or non- encephalitis (group E), had CSF endotoxin concentrations of less than 5 pg/ml. Despite a negative culture after antibiotic treatment in group A patients, endotoxin was cleared slowly from the CSF. A clearing of endotoxin from CSF was followed by alleviation of fever with a more gradual decline in CRP values. In 2 cases of group C, the negative bacterial culture appeared to be attributable to the previous treatment with antibiotics. However, these patients had high CSF endotoxin levels, indicating gram negative bacterial meningitis. In 17 CSF specimens from 5 patients of group A, in whom Haemophilus influenzae was detected on admission, an additional a latex agglutination test for the detection of H. influenzae polysaccharide antigen was performed. Only 3 specimens from 3 patients with CSF endotoxin concentrations of more than 80 pg/ml had a positive agglutination test. These results suggest that quantitation of endotoxin concentrations is useful for the diagnosis of gram-negative meningitis. And also, the clearance of endotoxin from CSF during treatment appears to be useful in determining the timing of when antibiotic should be stopped.
Asunto(s)
Endotoxinas/líquido cefalorraquídeo , Prueba de Limulus , Meningitis Bacterianas/diagnóstico , Adolescente , Niño , Preescolar , Infecciones por Bacterias Gramnegativas , Humanos , Lactante , Pruebas de Fijación de Látex , Meningitis Bacterianas/microbiología , SupuraciónRESUMEN
Pro- and antiinflammatory cytokines and mediators were measured in 39 patients with acute life-threatening meningococcal infections classified into 3 groups: A, meningitis without shock (n = 20); B, meningitis with shock (n = 9); and C, shock without meningitis (n = 10). The plasma concentrations of proinflammatory endotoxin, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-8 and antiinflammatory cytokines and mediators IL-1 receptor antagonist, IL-10, and soluble TNF receptors p55 and p75 were strongly associated with this classification; the highest concentrations were in group C. IL-4 was not measurable. IL-1 beta was increased only in rapidly fatal cases. In addition, cerebrospinal fluid (CSF) was analyzed in 21 patients for TNF-alpha and its soluble receptors. In CSF, these compounds were mainly increased in group A, reflecting an intrathecal compartmentalized cytokine production. It is concluded that both pro- and antiinflammatory mediators are simultaneously increased and are strongly associated with a classification based on simple clinical parameters.
Asunto(s)
Citocinas/análisis , Infecciones Meningocócicas/inmunología , Adolescente , Adulto , Niño , Preescolar , Citocinas/sangre , Citocinas/líquido cefalorraquídeo , Endotoxinas/sangre , Endotoxinas/líquido cefalorraquídeo , Femenino , Humanos , Lactante , Recién Nacido , Interleucinas/sangre , Interleucinas/líquido cefalorraquídeo , Masculino , Meningitis Bacterianas/inmunología , Meningitis Bacterianas/mortalidad , Infecciones Meningocócicas/mortalidad , Persona de Mediana Edad , Receptores del Factor de Necrosis Tumoral/análisis , Índice de Severidad de la Enfermedad , Choque Séptico/inmunología , Choque Séptico/mortalidad , Tasa de Supervivencia , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/análisisRESUMEN
The modernized limulus lysate assay on cerebrospinal fluid pretreated by the new perchloric acid (PCA) treatment was evaluated in one patient with Escherichia coli meningitis and four non-meningitis patients. The endotoxin (ET) concentration was much higher by the new PCA treatment than by the ordinary dilution method in the exacerbation phase of E. coli meningitis. The recovery rate of added ET also demonstrated the superiority of the new PCA treatment.
Asunto(s)
Endotoxinas/líquido cefalorraquídeo , Escherichia coli , Prueba de Limulus/métodos , Meningitis Bacterianas/diagnóstico , Percloratos , Colorimetría , Femenino , Humanos , Lactante , Meningitis Bacterianas/líquido cefalorraquídeoRESUMEN
In a rabbit Escherichia coli meningitis model, endotoxin liberation and concentrations of leukocytes, tumor necrosis factor (TNF), and lactate were compared after a single intravenous dose of cefotaxime, cefpirome, meropenem, chloramphenicol, or gentamicin. These antibiotics caused a 2- to 10-fold increase in cerebrospinal fluid concentrations of free (filterable) endotoxin within 2 h of starting treatment. By contrast, free endotoxin concentrations increased almost 100-fold in untreated animals 4 h later as bacteria continued to multiply. An initial enhancement of inflammation in the central nervous system occurred in all treatment groups compared with untreated controls. No significant differences were observed between treatment groups except for lower TNF concentrations in chloramphenicol-treated animals. Antibiotic therapy in E. coli meningitis, irrespective of the agent used, may result in an increase in free endotoxin and enhancement of inflammation, but the amount of endotoxin liberated is considerably smaller than that shed by untreated bacteria.
Asunto(s)
Antibacterianos/farmacología , Endotoxinas/líquido cefalorraquídeo , Infecciones por Escherichia coli/metabolismo , Inflamación/metabolismo , Meningitis Bacterianas/metabolismo , Animales , Cefotaxima/farmacología , Cefalosporinas/farmacología , Cloranfenicol/farmacología , Infecciones por Escherichia coli/tratamiento farmacológico , Gentamicinas/farmacología , Masculino , Meningitis Bacterianas/tratamiento farmacológico , Meropenem , Conejos , Tienamicinas/farmacología , CefpiromaAsunto(s)
Encéfalo/anomalías , Parálisis Cerebral/fisiopatología , Trabajo de Parto Prematuro , Factor de Necrosis Tumoral alfa , Encéfalo/fisiopatología , Encefalopatías/etiología , Encefalopatías/fisiopatología , Endotoxinas/análisis , Endotoxinas/líquido cefalorraquídeo , Endotoxinas/toxicidad , Enterocolitis/complicaciones , Femenino , Enfermedades Urogenitales Femeninas/complicaciones , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Leucomalacia Periventricular/etiología , Masculino , Enfermedades Urogenitales Masculinas , Embarazo , Sepsis/complicacionesRESUMEN
24 hr and 27 hr after K1-positive E coli suspended in 0.25 ml of saline (E coli 8 x 10(7)/ml) was injected into the cisterna magna of Chinese rabbits, the levels of bacterial titer, endotoxin, malondialdehyde (MDA), lactate and lactic dehydrogenase (LDH) of the cerebrospinal fluid (CSF) were increased significantly. After ampicillin therapy alone for 3 hr, the level of CSF bacterial titer was decreased and that of LDH increased, but the others didn't change significantly. After anisodamine and ampicillin therapy for 3 hr, the levels of CSF endotoxin and lactate concentrations were decreased from 3.2 +/- 0.6 to 2.1 +/- 0.9 log 10 IU/ml and from 8.6 +/- 2.0 to 6.5 +/- 1.8 mmol/L respectively. The CSF MDA concentration (0.31 +/- 0.07) was lower than that of the nontreatment group (0.59 +/- 0.25) or the ampicillin treatment group (0.59 +/- 0.21 nmol/ml) (P < 0.01 or 0.05). These results suggest that anisodamine combined with antibacterial therapy for experimental E coli meningitis is superior to antibacterial treatment in efficacy.
Asunto(s)
Ampicilina/administración & dosificación , Infecciones por Escherichia coli/tratamiento farmacológico , Meningitis Bacterianas/tratamiento farmacológico , Alcaloides Solanáceos/administración & dosificación , Vasodilatadores/administración & dosificación , Animales , Quimioterapia Combinada , Endotoxinas/líquido cefalorraquídeo , Infecciones por Escherichia coli/líquido cefalorraquídeo , Femenino , L-Lactato Deshidrogenasa/líquido cefalorraquídeo , Masculino , Malondialdehído/líquido cefalorraquídeo , Meningitis Bacterianas/líquido cefalorraquídeo , Meningitis Bacterianas/microbiología , ConejosRESUMEN
Endotoxin concentrations were measured in paired samples of cerebrospinal fluid from 38 patients with Haemophilus influenzae type b meningitis. On admission, the median concentration of endotoxin in cerebrospinal fluid was 104 ng/mL and decreased rapidly in follow-up samples. From 17 to 48 hours after admission, 50% of the patients had concentrations of less than 1 ng/mL. Endotoxin concentrations correlated significantly with concentrations of interleukin 1 beta, protein, and glucose in cerebrospinal fluid, duration of secondary fever, and neurologic abnormalities during hospitalization and on follow-up examinations. Twenty-eight percent of patients with endotoxin concentrations of 100 ng/mL or more on admission had long-term complications, compared with none of those with lower endotoxin concentrations (relative risk, 2.31; 95% confidence interval, 1.53 to 3.48). These results indicate that quantitation of endotoxin in cerebrospinal fluid could be a valuable aid in identifying those children at increased risk of complications during Haemophilus influenzae type b meningitis and provide additional evidence that the Haemophilus influenzae type b meningitis lipo-oligosaccharide is important in the pathogenesis of meningitis.
Asunto(s)
Endotoxinas/líquido cefalorraquídeo , Meningitis por Haemophilus/líquido cefalorraquídeo , Enfermedades del Sistema Nervioso/epidemiología , Animales , Proteínas del Líquido Cefalorraquídeo/análisis , Preescolar , Dexametasona/farmacología , Dexametasona/uso terapéutico , Modelos Animales de Enfermedad , Femenino , Estudios de Seguimiento , Glucosa/líquido cefalorraquídeo , Humanos , Lactante , Interleucina-1/líquido cefalorraquídeo , Recuento de Leucocitos , Lipopolisacáridos/líquido cefalorraquídeo , Lipopolisacáridos/efectos de los fármacos , Masculino , Meningitis por Haemophilus/complicaciones , Meningitis por Haemophilus/tratamiento farmacológico , Enfermedades del Sistema Nervioso/etiología , Pronóstico , Estudios Prospectivos , Conejos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factor de Necrosis Tumoral alfa/líquido cefalorraquídeoRESUMEN
In prospective studies, tumor necrosis factor (TNF alpha) was detected in cerebrospinal fluid (CSF) of 33 of 38 children with bacterial meningitis (BM) but in none of 15 with viral meningitis/encephalitis (P less than .001). BM CSF TNF alpha (less than 35 to greater than 25,500 pg/ml) correlated with CSF bacterial density (P less than .01), CSF protein (P less than .001), endotoxin (LPS) in gram-negative disease (P less than .01), and consecutive febrile hospital days (P less than .001); initial CSF TNF alpha greater than 1000 pg/ml was associated with seizures (P less than .05). Only 5 children with BM (13%) had detectable plasma TNF alpha activity on admission. A higher proportion who died had detectable plasma TNF alpha activity compared with survivors (3/4 vs. 2/34, P less than .005). Platelet-activating factor (PAF) in CSF was higher in 19 children with Haemophilus influenzae meningitis than in 17 controls (P less than .01) and correlated with bacterial density (P less than .01), CSF LPS (P less than .01), CSF TNF alpha levels (P less than .01), and the Herson-Todd severity score (P less than .01). Elevated CSF TNF alpha and PAF are often present in children with BM and are associated with seizures and severity of disease. Detectable CSF TNF alpha appears to distinguish BM from viral meningitis.
Asunto(s)
Meningitis/líquido cefalorraquídeo , Factor de Activación Plaquetaria/líquido cefalorraquídeo , Factor de Necrosis Tumoral alfa/líquido cefalorraquídeo , Adolescente , Bacterias/crecimiento & desarrollo , Líquido Cefalorraquídeo/microbiología , Proteínas del Líquido Cefalorraquídeo/líquido cefalorraquídeo , Niño , Preescolar , Endotoxinas/líquido cefalorraquídeo , Humanos , Lactante , Lipopolisacáridos/líquido cefalorraquídeo , Meningitis/complicaciones , Meningitis por Haemophilus/líquido cefalorraquídeo , Meningitis por Haemophilus/complicaciones , Estudios Prospectivos , Convulsiones/etiologíaRESUMEN
Total, cell-free, and cell-bound endotoxin and bacterial density were measured in cerebrospinal fluid (CSF) of 22 children with Hemophilus influenzae meningitis. Also the effect of ceftriaxone on CSF endotoxin levels was investigated in eight patients by reexamining their CSF 2-6 h after the initial dose. Initial CSF bacterial density correlated with initial CSF endotoxin levels (P less than .001). Ceftriaxone induced a marked increase of free endotoxin in CSF, from an initial (mean +/- SE) 0.75 +/- 0.21 to 1.29 +/- 0.23 log10 ng/ml (P less than .01). This increase correlated positively with the number of bacteria killed in the CSF (P less than .01). The increase in free endotoxin was associated with an increase in mean CSF lactate levels from 8.5 to 9.7 units/l (P less than .05) and mean lactate dehydrogenase levels from 102 to 180 mmol/l (P less than .02) and a decrease in mean CSF glucose from 1.17 to 0.46 mmol/l (P less than .05). Initial CSF total endotoxin concentrations correlated both with the Herson-Todd clinical severity score (P less than .001) and with the number of febrile hospital days (P less than .001). These findings suggest that highly bactericidal agents initially lead to release of free endotoxin from gram-negative organisms into CSF, with associated enhanced inflammatory response by the host.
Asunto(s)
Ceftriaxona/uso terapéutico , Endotoxinas/líquido cefalorraquídeo , Haemophilus influenzae , Meningitis por Haemophilus/líquido cefalorraquídeo , Ceftriaxona/administración & dosificación , Líquido Cefalorraquídeo/microbiología , Preescolar , Glucosa/líquido cefalorraquídeo , Humanos , Lactante , Inyecciones Intravenosas , L-Lactato Deshidrogenasa/líquido cefalorraquídeo , Lactatos/líquido cefalorraquídeo , Lipopolisacáridos/líquido cefalorraquídeo , Meningitis por Haemophilus/tratamiento farmacológico , Punción EspinalAsunto(s)
Cloranfenicol/uso terapéutico , Endotoxinas/metabolismo , Haemophilus influenzae/metabolismo , Meningitis por Haemophilus/tratamiento farmacológico , Animales , Cloranfenicol/farmacología , Endotoxinas/líquido cefalorraquídeo , Haemophilus influenzae/efectos de los fármacos , Humanos , Lactante , Recién Nacido , Masculino , Meningitis por Haemophilus/microbiología , ConejosRESUMEN
Intraventricular gentamicin therapy in infants with gram-negative enteric bacillary meningitis and ventriculitis is associated with increased mortality. Therefore, endotoxin, interleukin-1 beta, and cachectin (tumor necrosis factor) concentrations in ventricular cerebrospinal fluid from 21 infants (11 received intravenous antibiotics alone and 10 received intraventricular gentamicin also) were determined and correlated with outcome and other ventricular cerebrospinal fluid indexes of inflammation. Mean interleukin-1 beta concentrations in ventricular cerebrospinal fluid correlated significantly with adverse outcome and with mean concentrations of endotoxin, white blood cells, and protein and inversely with glucose concentrations. Mean and peak endotoxin and interleukin-1 beta concentrations were significantly higher in infants who received intraventricular gentamicin and intravenous antibiotics than in infants given intravenous antibiotics alone. Intraventricular gentamicin may have caused release of endotoxin from gram-negative bacilli in ventricular cerebrospinal fluid, resulting in increased interleukin-1 beta concentrations and inflammation, which could have contributed to the poor outcome in these patients.
Asunto(s)
Ventrículos Cerebrales , Encefalitis/líquido cefalorraquídeo , Endotoxinas/líquido cefalorraquídeo , Infecciones por Enterobacteriaceae/líquido cefalorraquídeo , Gentamicinas/administración & dosificación , Interleucina-1/líquido cefalorraquídeo , Meningitis/líquido cefalorraquídeo , Líquido Cefalorraquídeo/citología , Proteínas del Líquido Cefalorraquídeo/metabolismo , Humanos , Lactante , Recién Nacido , Inyecciones Intraventriculares , Recuento de Leucocitos , Factor de Necrosis Tumoral alfa/líquido cefalorraquídeoRESUMEN
We investigated the effect of cefotaxime and chloramphenicol on endotoxin concentrations in cerebrospinal fluid (CSF) and on the development of brain edema in rabbits with Escherichia coli meningitis. Both antibiotics were similarly effective in reducing bacterial titers. Cefotaxime, but not chloramphenicol, induced a marked increase of endotoxin in CSF, from log10 1.5 +/- 0.8 to log10 2.8 +/- 0.7 ng/ml (P less than .01). This result was associated with an increase in brain water content (405 +/- 12 g of water/100 g of dry weight compared with 389 +/- 8 g in untreated controls; P less than .01), whereas in animals treated with chloramphenicol, brain water content was identical to controls. The cefotaxime-induced increase in endotoxin concentration and brain edema were both neutralized by polymyxin B, which binds to the lipid A moiety of endotoxin, or by a monoclonal antibody to lipid A. These results indicate that treating gram-negative bacillary meningitis with selected antibiotics induces increased endotoxin concentrations in CSF that are associated with brain edema.
Asunto(s)
Antibacterianos/uso terapéutico , Edema Encefálico/etiología , Endotoxinas/líquido cefalorraquídeo , Infecciones por Escherichia coli/tratamiento farmacológico , Meningitis/tratamiento farmacológico , Animales , Anticuerpos Monoclonales/uso terapéutico , Cefotaxima/uso terapéutico , Cloranfenicol/uso terapéutico , Escherichia coli , Infecciones por Escherichia coli/líquido cefalorraquídeo , Infecciones por Escherichia coli/complicaciones , Lípido A/inmunología , Meningitis/líquido cefalorraquídeo , Meningitis/complicaciones , Polimixina B/uso terapéutico , ConejosRESUMEN
A retrospective review of data from two institutions demonstrated that the Limulus amebocyte lysate test was a simple and cost-effective means to screen cerebrospinal fluids (CSF) for Gram-negative agents of meningitis. Results of either gelation Limulus amebocyte lysate (LAL) or chromogenic Limulus amebocyte lysate (CLAL) tests on 1504 CSF were evaluated along with results of antigen detection tests [ADT; either latex agglutination (LA) or counterimmunoelectrophoresis (CIE)], cultures, and Gram-stains. All 127 CSF positive for Haemophilus or Neisseria by culture and/or ADT were also positive by Limulus test (100%). The sensitivities of Gram stain examination, culture, LA, and CIE for these two pathogens were 81%, 91%, 86%, and 63%, respectively. The Limulus test on lumbar CSF was positive in 67% of cases with other Gram-negative bacillary meningitis, in 33% of cases with Gram-negative bacillary abscess or ventriculitis, in none of the cases with Gram-positive, mycobacterial, treponemal, fungal, or viral meningitis, and in 1% of cases with either normal or otherwise negative bacteriologic findings. Overall, sensitivity and specificity of the Limulus test were 97% and 99%, respectively. The cost of either version of the Limulus test was less than 15% of the cost of ADT batteries for Haemophilus and Neisseria. Based on its sensitivity for Haemophilus and Neisseria in CSF, we propose its use as a cost-effective screen to minimize the need for the more expensive ADT batteries.
Asunto(s)
Endotoxinas/líquido cefalorraquídeo , Prueba de Limulus , Meningitis por Haemophilus/diagnóstico , Meningitis Meningocócica/diagnóstico , Meningitis/diagnóstico , Adulto , Niño , Análisis Costo-Beneficio , Contrainmunoelectroforesis , Bacterias Gramnegativas , Humanos , Pruebas de Fijación de Látex , Meningitis/líquido cefalorraquídeo , Meningitis por Haemophilus/líquido cefalorraquídeo , Meningitis Meningocócica/líquido cefalorraquídeoRESUMEN
Contraindications to performing a lumbar puncture include local infection, intracranial hypertension and complete spinal block. Routine parameters include pressure, appearance, glucose, protein and cytology. Specific studies such as antigen-antibody tests may identify infectious agents. The color of the CSF may indicate infection, previous hemorrhage or, rarely, metastatic melanoma. The IgG-albumin index is useful when there is inflammation, as in multiple sclerosis.
Asunto(s)
Enfermedades del Sistema Nervioso Central/líquido cefalorraquídeo , Líquido Cefalorraquídeo/citología , Proteínas del Líquido Cefalorraquídeo , Contrainmunoelectroforesis , Criptococosis/líquido cefalorraquídeo , Endotoxinas/líquido cefalorraquídeo , Glucosa/líquido cefalorraquídeo , Humanos , Inmunoglobulinas/líquido cefalorraquídeo , Presión Intracraneal , Prueba de Limulus , Meningitis/líquido cefalorraquídeo , Neurosífilis/líquido cefalorraquídeo , Punción Espinal/efectos adversosRESUMEN
Detection of endotoxinlike activity in cerebrospinal fluid by Limulus amebocyte lysate gelation has been suggested as a useful technique for the diagnosis of gram-negative bacterial meningitis. We prospectively screened 1,503 cerebrospinal fluid specimens with a Limulus amebocyte lysate microassay. The limit of sensitivity of the assay was 0.01 ng/ml. All specimens that were positive for endotoxinlike activity were subjected to confirmatory retesting, after which 38 (86%) remained positive. Comparison with available culture results revealed that 33 of 38 specimens (86%) were culture positive; 3 of the 5 culture-negative specimens were from patients on therapy for gram-negative bacterial meningitis, and 1 was from a neonate. The overall specificity of confirmed positive tests was 99.5%, with a positive predictive value of 97.3%. There was one false-negative specimen, giving an overall sensitivity of 97.3% and a negative predictive value of 99.9%. Endotoxinlike activities of greater than or equal to 150 ng/ml correlated with present illness of less than 2 days' duration (P = 0.024), elevated cerebrospinal fluid protein (P less than 0.05), and seizures (P = 0.004); levels of greater than or equal to 3,000 ng/ml correlated with neutropenia (P = 0.032), and levels of greater than or equal to 3.2 X 10(6) ng/ml correlated with death (P = 0.001). We conclude that the Limulus amebocyte lysate microslide gelation test has prognostic value as a sensitive, specific, simple, inexpensive screening test for gram-negative bacterial meningitis.