Presentation and outcome of sporadic acute bacterial meningitis in children in the African meningitis belt: recent experience from northern Nigeria highlighting emergent factors in outcome

Peptides consisting solely of D-amino acids (D-peptides) as opposed to their L-counterparts (L-peptides) are resistant towards proteolytic degradation in the organism and may therefore be useful in future efforts to develop new stable peptide-based drugs. Using the random synthetic peptide library technique several L- and D-peptides, capable of binding to both avidin and streptavidin, were found. The L-peptides contained the previously described HPQ/M motifs, and among the D-peptides three binding motifs could be identified, of which the most frequently found one contained an N-terminal aliphatic hydrophobic amino acid (V, L or I) and an aromatic amino acid (Y or F) on the second position. At the third position in this motif several different amino acid residues were found, although N was the most frequent. Peptides representing two of the D-motifs were synthesized as well as peptides containing the HPQ/M motifs, and their binding properties were examined. Although the D-peptides were originally selected using avidin they also inhibited binding between immobilized biotin and soluble streptavidin as well as avidin. The IC50 of some of the peptides were approximately 10(5) times higher than the IC50 for biotin but some had a lower IC50 than iminobiotin. The D-peptides, which were originally selected from the library using avidin, could also inhibit the binding between streptavidin and biotin. Likewise, L-peptides selected from a library screened with streptavidin, could inhibit the binding of both streptavidin and avidin to immobilized biotin. Furthermore, the D-peptide, VFSVQSGS, as well as biotin could inhibit binding of streptavidin to an immobilized L-peptide (RYHPQSGS). This indicates that the biotin-like structure mimicked by these two seemingly very different peptides may react with the same binding sites in the streptavidin molecule.     

Basic fibroblast growth factor in experimental and clinical bacterial meningitis

Basic fibroblast growth factor (bFGF), a neurotrophic factor in the CNS, is expressed at high levels in response to seizures or strokes. We examined the expression of bFGF during experimental bacterial meningitis and the levels of bFGF in the cerebrospinal fluid (CSF) of children with bacterial meningitis. For the experimental study, a mouse model of meningitis was established by intracranial injection of Streptococcus pneumoniae. Twenty-four hours after induced meningitis, the brains were sectioned and stained immunohistochemically for bFGF. Neutrophils and macrophages infiltrating the leptomeninges and the ventricles exhibited strong bFGF immunoreactivity. The neurons in the areas adjacent to the inflamed ventricles also showed enhanced bFGF expression. For the clinical study, we used an enzyme immunoassay to measure bFGF in CSF in 18 children with bacterial meningitis, 12 with aseptic meningitis, and 18 controls. The CSF levels of bFGF were twice as high in children with bacterial meningitis (medians 6.75-7.21 pg/mL) compared with those who had aseptic meningitis (2.9 pg/mL) or in control subjects (2.65 pg/mL, p < 0.0001, respectively). In patients with bacterial meningitis who survived, CSF bFGF decreased significantly after 24-50 h of antibiotic therapy (p < 0.0005). Patients who developed major sequelae or died had much higher levels of CSF bFGF than those without (134.9 pg/mL versus 7.38 pg/mL, p < 0.05). These findings of enhanced immunoreactivity of bFGF in experimental bacterial meningitis and an association of CSF levels of bFGF with disease severity in childhood bacterial meningitis suggest a biologic role for this neurotrophic factor in the pathophysiology of bacterial meningitis.     

Acute bacterial meningitis in adults: a clinical and developmental analysis of 100 cases

BACKGROUND: Characterize clinical findings and outcome of acute bacterial meningitis (ABM) in adults, with special emphasis on nosocomial meningitis and meningitis in the elderly. METHODS: We reviewed the charts of all persons 14 years of age or older in whom ABM was diagnosed in our hospital during a 12 and a half-year period. RESULTS: Ninety-seven patients were treated for 100 episodes of ABM, of which 23 percent were nosocomial and 27 percent occurred in elderly persons. Predisposing factors were present in 59 percent of the episodes. Fifty-four percent had the classic triad of fever, nuchal rigidity, and change in mental status. Cerebrospinal fluid pleocytosis with a neutrophilic predominance, hypoglycorrhachia, and elevated protein levels were present in 62 percent of the episodes. A pathogen was identified in 62 percent of the cases, in a higher frequency in elderly persons (p < 0.05) and in patients who had not received antibiotics before the lumbar puncture (p < 0.05). Causal agents more frequently identified were: Streptococcus pneumoniae (27 percent) in community-acquired meningitis, coagulase-negative Staphylococci (35 percent) in nosocomial meningitis, and Strep. pneumoniae (33 percent) in elderly persons. Central nervous system (CNS) complications occurred in 18 percent of episodes, and 15 percent developed systemic complications. The overall mortality rate was 9 percent, higher among patients in whom CNS complications began within 24 hours of admission (p < 0.05). CONCLUSIONS: A high proportion of cases of ABM in adults are nosocomial, or affect elderly persons. The fatality rate is high, particularly among those who develop CNS complications at the onset of the disease.     

The effect of interleukin-10 on meningeal inflammation in experimental bacterial meningitis

Interleukin-10 (IL-10) is a cytokine with antiinflammatory effects. In a rabbit model of meningitis, IL-10 was given intracisternally or intravenously to evaluate the impact on inflammation induced by lipooligosaccharide (LOS), Haemophilus influenzae type b (Hib), or Listeria monocytogenes. Intracisternal IL-10 in concentrations >1 microg significantly reduced tumor necrosis factor-alpha (TNF-alpha) and lactate values in cerebrospinal fluid (CSF). Intravenous IL-10 (1 mg/kg) in two doses after intracisternal LOS significantly reduced CSF TNF-alpha and lactate. When Hib was used, animals were treated with ceftriaxone and dexamethasone with or without IL-10 (1 mg/kg). TNF-alpha was significantly reduced in animals treated with IL-10, dexamethasone, or both compared with levels in rabbits receiving ceftriaxone alone. Comparable results were obtained when L. monocytogenes was inoculated and animals were treated with ampicillin with or without IL-10, dexamethasone, or nothing. In conclusion, IL-10 modulates CSF TNF-alpha concentrations in experimental LOS, Hib, or L. monocytogenes meningitis. The maximal inhibitory effect was seen when IL-10 and dexamethasone were combined.     

The value of C-reactive protein for the differentiation of bacterial meningitis from viral meningitis

In order to differentiate bacterial meningitis versus viral meningitis, we have comparatively tested the efficacy of the following tests: C-reactive protein (CRP), erythrocytes sedimentation rate (ESR), fever, level of glucose in cerebro-spinal fluid (CSF), glucose in CSF/glycemia ratio, number of white blood cells in peripheric blood, percentage of neutrophils in peripheric blood, level of proteins in CSF and number of nucleated cells in CSF for a group of 49 patients, both children and adults with central nervous system infection (37 patients with bacterial meningitis and 12 with viral meningitis) hospitalised between May 1993 and July 1994 in Clinical Hospital for Infectious Diseases in Ia?i. The mean value of CRP in bacterial meningitis patients was 8.78 mg%, contrasting with the mean value of CRP = 1.92 mg% recorded in patients with viral meningitis. Ten out of 37 bacterial meningitis patients presented a CRP concentration < 1.85 mg%. All these 10 patients have already had an antibiotic treatment at the moment of the assay. One out of 12 cases of viral meningitis had a value of CRP = 3.3 mg%, all the remainder cases having values under 1.85 mg%. We recorded highly significant differences between the two patient groups for CRP (p < 0.001), ESR (p < 0.01), protein concentration in CSF (p < 0.001) and number of nucleated cells in CSF (p < 0.001). Differences recorded for fever, concentration of glucose in CSF, glucose in CSF/glycemia ratio, number of leucocytes in peripheric blood and percentage of neutrophils in peripheric blood, were not significant (p > 0.5). Data were analysed also by box-plot method which facilitates the visual appraisal of the differences recorded between the two aetiological groups. In conclusion, assays of CRP and ESR may be used as differentiation tests for bacterial meningitis versus viral meningitis, when assay is done before the antibiotic treatment, being sufficient sensitive, and easy to perform.     

Recent bacterial and viral infection is a risk factor for cerebrovascular ischemia: clinical and biochemical studies

Inbred mice vary in susceptibility to colon carcinogens such as 1,2-dimethylhydrazine (DMH). Differential susceptibility may depend, in part, on formation of promutagenic DNA methyl adducts within target colonic mucosa. The present study was undertaken to evaluate the extent of DNA adduct formation in susceptible (SWR) and resistant (AKR) mice acutely exposed to the colon carcinogen azoxymethane (AOM), a direct metabolite of DMH. In the first experiment, 8-week-old SWR and AKR mice were treated i.p. with 20 mg/kg AOM and sacrificed 6 h later. DNA was isolated from distal colon and liver, and O6-methylguanine (O6-MeGua) adduct levels were assessed by immunoslot blot (ISB) analysis, using a monospecific antibody raised against O6-methyldeoxyguanosine. HPLC-fluorescence detection was also used to quantitate 06-MeGua and 7-methylguanine (7-MeGua), and to generate standard curves. At 6 h, both O6-MeGua and 7-MeGua were significantly higher (2- to 3-fold, p < 0.05) in AKR colon, while an opposite pattern was found in liver. In Experiment 2, mice were injected with AOM (20 mg/kg) and euthanized 12 and 48 h later. At 12 h, O6-MeGua levels were higher in colons (1.4-fold) of SWR mice. Forty-eight hours after treatment, however, adduct levels in colon were markedly (5-fold) reduced in SWR but were unchanged from 12 h in AKR. To further compare activation of AOM in both strains, colon microsomes were incubated with AOM and calf thymus DNA. Comparable levels of O6-MeGua were detected by ISB, demonstrating equivalent metabolic capacity in both SWR and AKR mice. These studies suggest that differential susceptibility to AOM-induced colon carcinogenesis is not based on initial target tissue DNA alkylation and unlikely to depend on differential metabolic capacity.     

Mixed bacterial meningitis: a complication of ventriculo- and lumboperitoneal shunts

Infectious complications of ventriculo- and lumboperitoneal shunts in two patients are presented. Cerebrospinal fluid infection due to aerobic and anaerobic enteric flora was characteristic of each case. Both infections occurred several months after shunt surgery and were associated with colonic perforation by the distal limb of the peritoneal catheter. These cases emphasize this unusual hazard of peritoneal shunts and demonstrate methods for diagnosis and effective therapy.     

Primary intraventricular hemorrhage in adults: clinical features, risk factors, and outcome

BACKGROUND AND PURPOSE: Nontraumatic primary intraventricular hemorrhage in adults is uncommon. The purpose of this study was to identify clinical features, risk factors, and outcome of primary intraventricular hemorrhage in adults. METHODS: We identified computed tomography scans for nontraumatic primary intraventricular hemorrhage performed between 1982 and 1993 at our institutions and reviewed medical records to determine clinical features, risk factors, and outcomes of these patients. RESULTS: Of 14 cases studied, the onset of symptoms was acute in all and the most common symptom was headache (78%), followed by nausea/vomiting (71%), and mental status change (71%). Seizures as well as focal neurologic deficits were uncommon. The associated risk factors were hypertension in 7 cases, aneurysm or arteriovenous malformation in 5, coagulopathy in 1, and fibromuscular dysplasia in 1 case. Five patients died acutely, and all of the survivors returned to functional independence. The patients with lethargy, pupillary and extraocular movement abnormalities, quadriparesis, hydrocephalus, and aneurysmal intraventricular hemorrhage had worse outcomes. CONCLUSION: Patients with nontraumatic primary intraventricular hemorrhage present with sudden onset of diffuse neurologic symptoms. The mortality in early phase is high (36%) and the prognosis for survivors is good. Factors correlating with the outcome are discussed.     

Epidemiology and etiology of bacterial meningitis in postnatal period

In south-east Poland in the years 1993 till 1995 we observed a decreasing number of meningococcal meningitis in children and a growth of cases caused by Haemophilus influenzae. Changes in ethiology of bacterial meningitis should give a reason for epidemiological research in Poland because there is a chance to reduce number of patients when wider use of new vaccines is introduced.     

Salmonella meningitis: clinical experience of third-generation cephalosporins

Fifteen paediatric patients with Salmonella meningitis were retrospectively reviewed. Presenting symptoms and signs included fever, vomiting, seizures, poor activity, diarrhoea and bulging anterior fontanelle in most patients. Seven out of eight patients with prolonged fever for > 10 days had neurologic sequelae; therefore, prolonged fever is a significant prognostic factor of a poor outcome (p < 0.005). All 15 patients had a brain ultrasound or computed tomography in the acute stage and 11 patients had abnormal findings. The 14 surviving patients were treated with a third-generation cephalosporin for at least 3 weeks. Seven patients (47%) made complete recoveries; two of them were treated solely with a third-generation cephalosporin. Only one mortality (6%) occurred and there were no relapses. In conclusion, high frequencies of prolonged fever, neuroimaging abnormalities and neurologic sequelae were seen in patients with Salmonella meningitis treated with third-generation cephalosporins.     

An ELISA assay for the rapid diagnosis of acute bacterial meningitis

The de novo purine synthesis inhibitor 5,10-dideazatetrahydrofolate (DDATHF) has previously been shown to inhibit the growth of mouse L1210 and human CCRF-CEM leukemia cells. The present study demonstrates that both the 6R and 6S diastereomers of DDATHF are also cytotoxic to mammalian cells in a stereospecific manner. The cytotoxic potency of (6R)-DDATHF (also known as Lometrexol) towards different cell lines varied by approximately 14-fold and that of (6S)-DDATHF by as much as 156-fold. Compared to (6R)-DDATHF, (6S)-DDATHF was 6.0- and 7.2-fold more cytotoxic to human WiDr colon adenocarcinoma and Chinese hamster ovary (CHO) cells, respectively, and only 1.5- and 2.0-fold more cytotoxic to human T24 bladder carcinoma and mouse L1210 leukemia cells, respectively. However, compared to (6S)-DDATHF, (6R)-DDATHF was 8.7- and 6.9-fold more cytotoxic to C3H/10T1/2 clone 8 and clone 16 mouse fibroblasts, respectively. Weak inhibition of aminoimidazolecarboximide ribonucleotide formyltransferase (AICARFT, EC 2.1.2.3) appeared to have little role in the cytotoxicity of DDATHF diastereomers to WiDr cells during a 24-h exposure. Although glycinamide ribonucleotide formyltransferase (GARFT, EC 2.1.21) is the main biochemical target of DDATHF, DDATHF stereoisomers' cytotoxic potency showed no clear negative correlation with cellular GARFT levels. However, cellular folylpolyglutamate synthetase (FPGS, EC 6.3.2.17) levels correlated with cytotoxic potency in a positive manner. Surprisingly, two enzyme-dose/DDATHF LD90-response curves were observed for FPGS corresponding to differences in (6R) and (6S)-DDATHF cytotoxic potency among the six cell lines studied.     

Dexamethasone adjunctive therapy for bacterial meningitis in children: a retrospective study in Brazil

Contribution of a case report of megacalycosis in a nine and a half-year old male child, in whom the disorder was diagnosed by our team when he was only four. The intense colic pains experienced by the child together with the isotopic renogram non responsive to seguril typical of obstruction, raised the diagnosis of superimposed stenosis of the pyeloureteral attachment. As a result, an Anderson-Hynes pyeloplasty was performed. Post-operative status after four years is absolutely normal from both a clinical and scintiscan point of view.     

Dexamethasone therapy for bacterial meningitis in children: 2- versus 4-day regimen

Four-day dexamethasone therapy has been used to treat bacterial meningitis. This prospective, randomized study compared the effect of a 2-day versus a 4-day regimen. Children (n = 118, ages 2.5 months to 15 years) were evaluated; 50% of the cases were due to Neisseria meningitidis and 40% to Haemophilus influenzae type b. Patients were treated intravenously (iv) mainly with conventional antimicrobial therapy and were randomly assigned to receive dexamethasone, 0.15 mg/kg iv every 6 h for 2 or 4 days. The clinical response was similar for both dexamethasone regimens. The meningococcal meningitis patients survived without neurologic or audiologic sequelae. On long-term follow-up, neurologic sequelae or moderate or more severe unilateral or bilateral hearing impairment (or both) were found in 1.8% and 3.8% of patients treated with dexamethasone for 2 and 4 days, respectively. The 2-day regimen appears appropriate for the treatment of H. influenzae and meningococcal meningitis.     

Identifying international assignees at risk for premature departure: The interactive effect of outcome favorability and procedural fairness.

Two studies examined factors that predict expatriate managers' tendencies to think seriously about departing prematurely from their international assignments. Previous research (conducted outside of the expatriate context) has shown that individuals' willingness to stay with or leave their positions is an interactive function of outcome favorability and procedural fairness. A conceptually analogous interaction effect was found in the present studies. Whereas expatriates more seriously thought of departing prematurely when they perceived the non-work-related outcomes of their overseas assignments to be less favorable, this tendency was much less pronounced when procedural fairness was relatively high. Theoretical and practical implications are discussed, as are limitations of the studies and suggestions for future research. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Critical carotid artery stenosis: diagnosis, timing of surgery, and outcome

PURPOSE: Patients with critical carotid artery stenoses have been considered to be at high risk for carotid artery occlusion necessitating urgent or emergency endarterectomy once the stenosis is identified. Included in this group of patients are those with carotid string sign or atheromatous pseudoocclusion (APO). This review was conducted to determine the impact of the severity of stenosis including APO on the treatment and outcome of patients undergoing carotid endarterectomy. METHODS: The records of 203 consecutive carotid endarterectomies performed in 197 patients were reviewed in detail. Patients were stratified into a critical stenosis group (80% to 99% diameter) and noncritical stenosis group based on noninvasive vascular laboratory and carotid arteriography results. Comparisons were performed of demographic data, atherosclerotic risk factors, carotid artery disease presentation, interval between arteriography and endarterectomy, operative details, and surgical results between the critical and noncritical groups and between patients in the critical group with and without APO. RESULTS: Carotid endarterectomies were performed on 91 critical carotid artery stenoses and 112 noncritical stenoses. The groups did not differ significantly with regards to demographics, risk factors, carotid artery disease presentation, mean back pressure, and operative use of shunt or patch closure. For the critical group the interval between arteriography and endarterectomy was 8.63 +/- 2.38 days compared with 9.64 +/- 2.14 days for the noncritical group (mean +/- SEM, p = 0.75). No patient in either group progressed to occlusion in the interval between arteriography and endarterectomy. Perioperative strokes occurred in two patients (2%) in the critical group and four patients (3.6%) in the noncritical group (p = 0.09). Likewise, no significant difference was demonstrated in these variables when comparing patients with critical carotid artery stenosis and APO with those without APO. CONCLUSIONS: The presence of a critical carotid artery stenosis including APO did not impact on the treatment or outcome of patients requiring endarterectomy nor did it imply the need for emergency intervention to prevent thrombosis. Surgical intervention can proceed after evaluation and optimization of comorbid conditions without undue concern for interval thrombosis.