Biomedical subjects
Publications and source records attributed to M H Lebel.
Two children with Kawasaki disease initially had upper respiratory tract manifestations. The first was admitted with a diagnosis of uvulitis; in the second the clinical picture was characterized by supraglottic involvement, confirmed by direct laryngoscopic examination.
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Recent developments in the pathogenesis, epidemiology and therapy of bacterial meningitis are presented. The importance of interleukin-1 beta, tumor necrosis factor alpha, and prostaglandins as generators of inflammation within the central nervous system in animals and children is described. The role of mediators of inflammation such as dexamethasone in the experimental meningitis model and in clinical studies is reviewed. The optimal duration of therapy and the role of cephalosporins in bacterial meningitis are discussed.
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We conducted a third placebo-controlled, double-blind study of dexamethasone as adjunctive therapy for bacterial meningitis. Thirty-one patients received cefuroxime sodium (300 mg/kg per day in 3 doses) and dexamethasone phosphate (0.6 mg/kg per day in 4 doses for 4 days), and 29 received cefuroxime and placebo. The groups were comparable at the beginning of therapy. Magnetic resonance imaging performed between days 2 and 5 of therapy was used to assess brain water content indirectly. There were no differences between the 2 treatment groups with respect to the T1- or T2-weighted images. Fifty-two patients (88%) had normal magnetic resonance images; 5 patients had parietal or bifrontal extra-axial fluid collections, and 2 children had areas of abnormal signal intensity in the brain on T2-weighted images. Abnormal findings on magnetic resonance imaging did not alter clinical management, and there was no correlation between the results of magnetic resonance imaging and the outcome of meningitis. The number of patients in this study was too small to determine any statistically significant differences in rates of hearing impairment; however, the cerebrospinal fluid findings and clinical outcome in dexamethasone-treated patients further support the previously reported beneficial effect of corticosteroid treatment in patients with bacterial meningitis.
Because interleukin-1 beta (IL-1 beta) and cachectin (tumor necrosis factor) are thought to mediate the body's response to microbial invasion, we measured IL-1 beta and tumor necrosis factor concentrations in paired cerebrospinal fluid (CSF) samples (on admission to the hospital, CSF1; 18 to 30 hours later, CSF2) from 106 infants and children with bacterial meningitis. In CSF1, IL-1 beta was detected in 95% of samples; the mean (+/- 1 SD) concentration was 944 +/- 1293 pg/ml. Patients with CSF1 IL-1 beta concentrations greater than or equal to 500 pg/ml were more likely to have neurologic sequelae (p = 0.001). Tumor necrosis factor was present in 75% of CSF1 samples; the mean concentration was 787 +/- 3358 pg/ml. In CSF2 the mean IL-1 beta concentration was 135 +/- 343 pg/ml, and IL-1 beta concentrations correlated significantly with CSF2 leukocyte count, with glucose, lactate, protein, and tumor necrosis factor concentrations, and with neurologic sequelae. Tumor necrosis factor was detected in CSF2 specimens of 53 of 106 patients, with a mean concentration of 21 +/- 65 pg/ml. Of the 106 patients, 47 received dexamethasone therapy at the time of diagnosis. These patients had significantly lower concentrations of IL-1 beta and higher glucose and lower lactate concentrations in CSF2, and they had a significantly shorter duration of fever compared with the values in patients not treated with steroids (p less than or equal to 0.002). Our data suggest a possible role of IL-1 beta and tumor necrosis factor as mediators of meningeal inflammation in patients with bacterial meningitis, and might explain, in part, the beneficial effect of dexamethasone as adjunctive treatment in this disease.
To assess the comparative efficacy of cefuroxime and ceftriaxone for the treatment of bacterial meningitis, we reviewed the records from four prospective efficacy trials conducted at our institution. One hundred seventy-four infants and children received ceftriaxone and 159 received cefuroxime. The clinical characteristics of the two groups were comparable at admission. After 24 hours of therapy, routine cerebrospinal fluid cultures for all patients treated with ceftriaxone were sterile, whereas 9% of cerebrospinal fluid cultures were positive in cefuroxime-treated patients (p less than 0.001). More cefuroxime-treated patients had abnormal physical examinations at the time of discharge than did ceftriaxone-treated patients (39/159 vs 25/174, p = 0.02). At 6-week and 1-year follow-up examinations, there was no longer a statistically significant difference in the incidence of neurologic abnormalities between the two therapy groups, but the incidence of hearing impairment in one or both ears was higher in the cefuroxime (18%) than in the ceftriaxone (11%) treatment group. Both regimens are efficacious for the treatment of bacterial meningitis, but some patients may not respond as satisfactorily to cefuroxime as to ceftriaxone.
A retrospective review of children who needed mechanical ventilation for severe bronchiolitis identified 62 cases over a 10 year period. The mean age at initiation of ventilation was 73 days (range: 14-201). Compared with a group of 150 children in hospital for bronchiolitis but not transferred to the intensive care unit, these 62 cases were significantly younger (73.0 compared with 166.3 days), and smaller (4.5 compared with 6.8 kg), and significantly more had been born prematurely (40% compared with 16%). Taken independently, age, weight, and prematurity were significantly associated with the need for artificial ventilation, weight being the most important factor. Using stepwise logistic regression, prematurity in itself added to the quality of the prediction but age did not. The mean duration of mechanical ventilation was 105 hours (range 2-381). Duration of ventilation was significantly longer in children with a low gestational age at birth and a positive familial history of atopy. There were no deaths, and no patient developed pneumothorax or pneumomediastinum. Mechanical ventilation is well tolerated and safe in acute bronchiolitis.
To determine the clinical importance of CSF cultures that are persistently positive for pathogens in patients treated for meningitis with the new cephalosporins, the records of 301 infants and children with bacterial meningitis enrolled prospectively in four clinical efficacy trials of cefuroxime or ceftriaxone therapy were reviewed. CSF culture results were positive for 20 patients and they were sterile at 18 to 36 hours after start of therapy for 281 patients. Seizures, subdural effusions, and hemiparesis were found significantly more often during hospitalization in those with delayed sterilization of CSF. Children with persistently positive cultures had a significantly higher incidence of neurologic abnormalities at the time of hospital discharge (45% v 19%) and at follow-up (41% v 13%) and of moderate to profound hearing impairment (35% v 15%) than did those with prompt sterilization of CSF. Repeat CSF examination is a useful prognostic indicator in infants and young children with bacterial meningitis.
We enrolled 200 infants and older children with bacterial meningitis in two prospective double-blind, placebo-controlled trials to evaluate the efficacy of dexamethasone therapy in addition to either cefuroxime (Study 1) or ceftriaxone (Study 2). Altogether, 98 patients received placebo and 102 received dexamethasone (0.15 mg per kilogram of body weight every six hours for four days). At the beginning of therapy, the clinical and demographic characteristics of the patients in the treatment groups were comparable. The mean increase in the cerebrospinal fluid concentration of glucose and the decreases in lactate and protein levels after 24 hours of therapy were significantly greater in those who received dexamethasone than in those who received placebo (glucose, 2.0 vs. 0.4 mmol per liter [36.0 vs. 6.9 mg per deciliter], P less than 0.001; lactate, 4.0 vs. 2.1 mmol per liter [38.3 vs. 19.8 mg per deciliter], P less than 0.001; and protein, 0.64 vs. 0.25 g per liter [64.0 vs. 25.3 mg per deciliter], P less than 0.05). One patient in the placebo group in Study 1 died. As compared with those who received placebo, the patients who received dexamethasone became afebrile earlier (1.6 vs. 5.0 days; P less than 0.001) and were less likely to acquire moderate or more severe bilateral sensorineural hearing loss (15.5 vs. 3.3 percent; P less than 0.01). Twelve patients in the two placebo groups (14 percent) had severe or profound bilateral hearing loss requiring the use of a hearing aid, as compared with 1 (1 percent) in the two dexamethasone groups (P less than 0.001). We conclude that dexamethasone is beneficial in the treatment of infants and children with bacterial meningitis, particularly in preventing deafness.