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)

Pharmacokinetic variables were studied in children with central nervous system infections who received a single dose of ceftriaxone sodium. After initial lumbar puncture of children with documented or suspected bacterial meningitis, ventriculitis, or both, therapy was initiated with i.v. ampicillin and chloramphenicol. Children were randomly selected to receive a single i.v. dose of ceftriaxone. Concentrations of ceftriaxone were measured in plasma at intervals from 0 to 720 minutes after the beginning of the infusion and in cerebrospinal fluid (CSF) at one to five hours after the dose. Blood samples were obtained immediately after the second lumbar puncture for assessment of drug penetration into CSF. Elimination rate constant, elimination half-life, apparent volume of distribution, and plasma clearance were determined from samples obtained 30-720 minutes after the start of the infusion. In two children with ventriculoperitoneal shunts, serial determinations of ceftriaxone in CSF were obtained. All eight children who received 75 mg/kg and five of eight who received 50 mg/kg had positive CSF cultures. Volume of distribution was less after the 50 mg/kg dose than after the 75 mg/kg dose. In the children with shunts, adequate CSF drug concentrations were maintained throughout 12 hours of testing. These data support a 12-hour dosage interval, but clinical studies are needed to evaluate efficacy of the drug at both 12-hour and 24-hour dosage regimens.
 ...
PMID:Single-dose plasma and cerebrospinal fluid pharmacokinetics of ceftriaxone in infants and children. 631 77

It would be easier and cheaper, and there would be less risk of cerebral oedema, if bacterial meningitis could be adequately treated without the intravenous administration of fluid. Fifty children with bacterial meningitis were treated with intramuscular injections of benzyl penicillin, probenecid given orally and chloramphenicol palmitate suspension given orally, and the outcome was evaluated prospectively. Seven (14%) of the 50 children died. In a control group of 50 children with bacterial meningitis treated with the intravenous administration of benzyl penicillin and chloramphenicol sodium succinate, the outcome was determined retrospectively. Twelve (24%) of the 50 children died. The difference in mortality rate was 10% +/- 15.7% (+/- 2 SE), which is not significant. Except in the rare case of a child with shock or persistent vomiting, bacterial meningitis can be effectively treated with six-hourly intramuscular injections of penicillin, and probenecid and chloramphenicol given orally.
 ...
PMID:Treatment of bacterial meningitis in children without intravenous fluids. 725 34

We have investigated the possible role of nitric oxide (NO) in the pathophysiology of bacterial meningitis (BM) by using the rat model of experimental BM. The nitrite concentration in cerebrospinal fluid (CSF) was used as a measure of NO production in vivo since NO rapidly degrades to nitrite and nitrate. Rats were inoculated intracisternally with live bacteria (5 x 10(6) CFU of Haemophilus influenzae type b strain DL42 or Rd-/b+/O2), with bacterial endotoxin (20 ng of DL42 lipooligosaccharide [LOS] or 200 ng of Escherichia coli lipopolysaccharide), or with a saline control vehicle. CSF samples were collected preinoculation and at the time of maximal alteration in blood-brain barrier permeability (BBBP). CSF [nitrite] was quantified by measuring A550 after addition of the Greiss reagent and comparison to a standard curve of sodium nitrite. Rats inoculated with either DL42, Rd-/b+/O2, LOS, or lipopolysaccharide demonstrated a significantly elevated mean peak CSF [nitrite] (8.34, 15.62, 10.75, and 10.44 mM, respectively) versus the concentration prior to treatment and/or those in saline-treated animals (5.29 and 5.33 mM, respectively; P < 0.05 for each comparison). We then determined if there was a correlation between CSF [nitrite] and percent BBBP (%BBBP) at various time points postinoculation with Rd-/b+/O2. %BBBP was defined as the concentration of systemically administered 125I-labeled bovine serum albumin in the CSF divided by the level of 125I-labeled bovine serum albumin in serum multiplied by 100. The mean %BBBP increased in tandem with the mean CSF [nitrite] (R = 0.84, P = 0.018), which peaked at 18 h in the absence of a change in the serum [nitrite]. Systemic administration of the NO synthase inhibitor N-nitro-L-arginine methyl ester demonstrated a significant reduction of mean CSF nitrite production (0.95 versus 6.0 mM in controls; P = 0.02) when administered intravenously to animals which had been inoculated intracisternally with 20 ng of LOS. Suppression of mean leukocyte pleocytosis (3,117 versus 11,590 leukocytes per mm3 in control LOS-challenged rats; P = 0.03) and mean alterations of BBBP (2.11 versus 6.49% in control LOS-challenged rats; P = 0.009) was observed concomitantly with decreased CSF [nitrite]. These results support the hypothesis that NO contributes to increased %BBBP in experimental BM.
 ...
PMID:Potential role of nitric oxide in the pathophysiology of experimental bacterial meningitis in rats. 755 88

Sixty children aged from 1 month to 12 years (mean (SD) 3.18 (3.49) years) with acute bacterial meningitis were studied for the incidence, clinical manifestations and outcome of the inappropriate secretion of antidiuretic hormone syndrome (SIADH). Serum sodium levels and osmolality of serum and urine were estimated on admission and on days 3 and 10. SIADH was diagnosed in 22 out of 60 cases (36.7%) on admission and in six of 48 cases (12.5%) on day 3. Hyponatraemia without SIADH, attributed to vomiting and fever, was detected in seven cases (11.7%). Serum sodium levels returned to normal within 48 hours in these cases. Serum osmolality and sodium levels took longer to return to normal values in patients with SIADH. However, none of the cases showed any evidence of SIADH on the 10th day. A significant correlation with SIADH was observed in cases with evidence of severe meningeal inflammation (p < 0.001). The incidence of SIADH was highest with Streptococcus pneumoniae (75%), followed by Haemophilus influenzae (57.1%). Overall mortality was 26.7%, and mortality was significantly higher (p < 0.001) in cases with SIADH, all of whom died during the 1st 72 hours. Ten out of 22 cases (45.4%) with SIADH who survived beyond the 1st 72 hours had an uneventful course even though all of them had biochemical evidence of SIADH on the 3rd day. Mortality was quite high also in children with severe malnutrition (75%) and in those with S. pneumoniae as the aetiological organism (75%).
 ...
PMID:Inappropriate secretion of antidiuretic hormone in acute bacterial meningitis. 767 22

Neisseria meningitidis is the etiologic agent of epidemic bacterial meningitis. Lipooligosaccharide (LOS) is a principal virulence factor associated with the organism, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of LOS has demonstrated that there is considerable microheterogeneity in the molecule. To begin our understanding of the nature of this heterogeneity, we identified a Tn916-generated LOS mutant of N. meningitidis NMB (serotype L3, monoclonal antibodies 3F11+, 6B4+, and 4C4-) that was designated NMB-SS3 (monoclonal antibodies 3F11-, 6B4-, and 4C4+). The transposon insertion was localized to the amino terminus of the functional copy of the UDP-Glc 4-epimerase gene (galE). UDP-Glc 4-epimerase (EC 5.1.3.2) activity was present in N. meningitidis NMB but not in NMB-SS3, indicating that the Tn916 insertion had abolished this activity. Mass spectrometric analysis of the LOS from strain NMB revealed multiple species of LOS, which is consistent with extensive microheterogeneity. While the most predominant structure was consistent with a terminal lacto-N-neotetrose structure found in other strains of N. meningitidis, Gal beta 1-->4GlcNAc beta 1-->3Gal beta 1-->4Glc-->(GlcNAc)-->Hep2PEA-->KDO2 (where Hep is heptose, PEA is phosphoethanolamine, and KDO is 2-keto-3-deoxymannooctulosonic acid), structures containing repetitive hexoses which are not precursors of this structure were also identified. Compositional analysis of LOS from strain NMB-SS3 revealed that there were no galactoses present in the structure. Mass spectrometric analysis of O-deacylated LOS revealed the presence of multiple species, with the predominant LOS species in this mutant strain formed by the Hex-->(HexNAc)-->Hep2PEA-->KDO2 (where Hex is hexose and HexNAc is N-acetylhexosamine) structure. However, LOS structures with repetitive hexoses, e.g., Hexn-->(HexNAc)-->Hep2PEA-->KDO2 (n = 2, 3, or 4), emanating from one or both heptoses were also identified. Since this mutant cannot synthesize UDP-Gal, these structures must repetitive glucoses. These data suggest that NMB has a glycosyltransferase capable of polymerizing glucose moieties as an alternative biosynthetic pathway to the wild-type lacto-N-neotetrose structure.
 ...
PMID:Microheterogeneity of Neisseria lipooligosaccharide: analysis of a UDP-glucose 4-epimerase mutant of Neisseria meningitidis NMB. 779 63

The endotoxins of bacteria are lipopolysaccharides which are released in the central nervous system during bacterial meningitis. Endotoxin titers in cerebrospinal fluid correspond to the appearance of severe neurological symptoms like seizures and coma. The pathogenic mechanism, however, by which endotoxins disturb neuronal function, is unclear. The functional deficit may originate either from direct alteration of neuronal excitability or from indirect effects mediated by glial cells. Therefore, we investigated the effects of lipopolysaccharides on electrophysiological properties of cortical neurons and astrocytes in separate cell cultures. Membrane potential, resistance and membrane currents of neurons were unaffected. By contrast, astrocytes depolarized markedly in a dose dependent manner (concentration range 1.0-10.0 micrograms/ml). The depolarization was Na+ dependent and amiloride sensitive (250 microM), both indicating an activation of an electrogenic sodium dependent transport system like the Na+/Ca2+ exchanger as a source of the depolarization. These results suggest that endotoxin induced neurological deficits are not caused by direct effects on neurons, but may result from an impaired glial cell function.
 ...
PMID:Bacterial endotoxins impair electrophysiological properties of cultured astrocytes but not of cultured neurons. 796 66

Sixty children with acute bacterial meningitis (ABM) were prospectively studied for their serum sodium values and cerebrospinal fluid (CSF), serum and urinary osmolality. The results have been compared with 20 age and nutritionally matched controls. Even though mean serum osmolality (283.2 +/- 13.84 mOsm/kg) and serum sodium levels (130.5 +/- 8.15 mEq/L) were significantly lower in ABM in comparison to controls (p < 0.05 and < 0.001, respectively), the overall mean CSF osmolality in patients with ABM (282.5 +/- 12.3 mOsm/kg) was not significantly different as compared to controls (288.2 +/- 7.89 mOsm/kg). As expected, cases of ABM with syndrome of inappropriate secretion of antidiuretic hormone (SIADH) had significantly lower CSF osmolality (272 +/- 9.42 mOsm/kg) as compared to those without SIADH (288.5 +/- 9.34 mOsm/kg) and controls (288.2 +/- 7.89 mOsm/kg). However, our observations indicate that whereas the mean CSF osmolality was lower than the serum osmolality in the control group as well as in ABM without SIADH, it was greater than serum osmolality in ABM with SIADH (p < 0.05). Our results suggest that in the presence of SIADH, hypo-osmolality of serum may eventually result in hypo-osmolality of CSF, but the fall in CSF osmolality is not of the same degree as that of serum. Low CSF osmolality was observed to be associated with an unfavorable prognosis (p < 0.05).
 ...
PMID:Cerebrospinal fluid osmolal changes in bacterial meningitis. 807 10

Neonatal bacterial meningitis remains a life-threatening infection, and severe neurologic sequelae may be left in survivors as well. The goal of the study was to develop and characterize a porcine model of the disease with intravital observation of the permeability changes in cerebral microvessels. Eighteen newborn piglets were given doses of 0 ng (group 1), 20 ng (group 2), and 200 ng (group 3) of Escherichia coli 0111 B4 endotoxin (LPS) intracisternally (n = 6 in each group). Cardiovascular parameters were without changes, but a compensated metabolic acidosis occurred in group 3 4 h after LPS injection. Using the open cranial window technique combined with fluorescence excitation, there was no blood-brain barrier leakage in pial-arachnoid microvessels for sodium fluorescein during the 4 h of experiments in group 1 piglets, whereas spotty extravasations occurred in group 2 and in group 3 after the LPS injections (70.5 +/- 10.5 and 55.2 +/- 4.1 min, respectively, mean +/- SEM). A dose-dependent increase in sodium fluorescein uptake in brain regions examined (parietal and occipital cortex, cerebellum, and periventricular white matter) was also found by fluorescence spectrophotometry. LPS-treated piglets had developed pleocytosis. Four h after the challenge, the white blood cell counts in cerebrospinal fluid were (mean +/- SD): group 1, 8.2 +/- 7.6 microL-1; group 2, 453 +/- 703 microL-1; and group 3, 1 027 +/- 620 microL-1, respectively, whereas there was no change in white blood cell count of peripheral blood samples.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Escherichia coli 0111 B4 lipopolysaccharide given intracisternally induces blood-brain barrier opening during experimental neonatal meningitis in piglets. 823 23

Since the mechanisms underlying hyponatraemia in meningitis are poorly understood, we retrospectively reviewed the records of 187 paediatric patients with bacterial meningitis treated at the Department of Pediatrics, University of Bern, Switzerland, between 1982 and 1994. The degree of dehydration calculated from naked weight on admission and at 5 days was consistently (by 2.8 x 10(-2) and significantly more pronounced in 30 hyponatraemic (plasma sodium 130 mmol l-1 or less) than in 157 normonatraemic patients (plasma sodium 131 mmol l-1 or more). Furthermore, a tendency towards reduced sodium excretion was noted in hyponatraemic patients. The results suggest that in bacterial meningitis hyponatraemia is mostly induced by clinically latent fluid volume depletion.
 ...
PMID:Evidence for fluid volume depletion in hyponatraemic patients with bacterial meningitis. 935 Sep 6

To evaluate the effects of bacterial meningitis on blood and CSF parameters, an experiment was conducted with five Iranian crossbred male calves. Blood and CSF samples were collected 3 times within a 5-day interval before the administration of bacteria for obtaining control values. Following the injection of E. coli, K12 into the cerebrospinal fluid from the lumbosacral space, samples were collected and clinical signs of meningitis were observed. Blood and CSF samples were obtained from the meningitis group 3 times at 1, 3, and 5 days post injection. The treatment of the infected calves using lincospectin and tetracycline was carried out immediately after the onset of clinical signs. After the treatment, blood and CSF samples were obtained 3 times during a 5-day period. Following the induction of meningitis, the number of WBCs, neutrophils, eosinophils and monocytes significantly increased (P < 0.05). However, the percent of lymphocytes decreased significantly (P < 0.05). The concentrations of glucose, potassium and activity of AST, LDH, CK significantly increased (P < 0.05). In contrast, the concentrations of phosphorous, sodium and magnesium significantly decreased (P < 0.05). Furthermore, following the induction of meningitis, the CSF was slightly xantochromic and turbid. The concentrations of protein, cholesterol, phosphorous, potassium, the activities of AST, LDH, CK, and the cell numbers in the CSF increased significantly (P < 0.05). In contrast, the concentration of glucose and pH in the CSF decreased significantly (P < 0.05). This study showed that bacterial meningitis can have profound effects on blood and CSF parameters which enable one to reach diagnosis.
 ...
PMID:Evaluation of hematological, serum biochemical and cerebrospinal fluid parameters in experimental bacterial meningitis in the calf. 912 83


<< Previous 1 2 3 4 5 6 Next >>