Efficacy of epinephrine with salbutamol in treatment of acute bronchiolitis.
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Biomedical subjects
Publications and source records attributed to F Rusconi.
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A combination of posttranslational modifications contributes to the high heterogeneity of brain tubulin in mammals. In this report, the structures of the detyrosinated carboxy-terminal peptides of alpha-tubulin from newborn and adult mouse brain were compared. The heterogeneity of these carboxy-terminal peptides was observed to increase from newborn to adult brain tubulin. The major part of this increased heterogeneity is due to the post-translational excision of Glu450, which makes alpha-tubulin nontyrosinatable (delta-2 tubulin). The structures of the polyglutamyl side chain of the bi- and triglutamylated peptides were analyzed in this work. In polyglutamylation of alpha-tubulin, the first glutamyl residue can only be amide-linked to the gamma-carboxyl group of Glu445, but the additional residues may be linked either to the gamma- or to the alpha-carboxyl groups of the preceding one. By optimized reverse-phase separations and comparison with synthetic peptides corresponding to all possible linkages for the biglutamylated (gamma 1 alpha 2, gamma 1 gamma 2) and triglutamylated (gamma 1 alpha 2 alpha 3, gamma 1 gamma 2 gamma 3, gamma 1 alpha 2 gamma 3, gamma 1 gamma 2 alpha 3, gamma 1 gamma 2 alpha 2) tubulin peptides, it was possible to conclude that the mode of linkage connecting the second and third additional glutamyl residues corresponds mostly to alpha-bond structures, for both newborn and adult mice.
Respiratory inductive plethysmography (RIP) is a simple technique for an objective, noninvasive assessment of thoracoabdominal asynchrony, which in turn is an indirect measure of airway obstruction. We evaluated different indices of asynchrony obtained by RIP before and after methacholine-induced airway obstruction. Bronchial obstruction was elicited by progressive doubling concentrations of methacholine until a > 15% fall in the transcutaneous oxygen tension (PtcO2) had developed. Maximal expiratory flow rates at functional residual capacity (FRC) (VmaxFRC) was obtained by the squeeze technique before and after the challenge. Fifteen infants with a history of wheezing were studied after sedation. Thoracoabdominal movements were recorded with RIP bands placed around either the upper or the lower ribcage (RC) and around the abdomen (AB). An inspiratory asynchrony index (IAI) and an expiratory asynchrony index (EAI) were calculated as determined by the lag of RC relative to AB at start of inspiration and of expiration, respectively. The total time in asynchrony (TTA: the percentage of time in which the RC and the AB signals were in opposite direction) and phi (an angle derived from a Lissajous loop) were also calculated. All subjects responded to the challenge. The median fall in PtcO2 following methacholine challenge was 23.6% and in VmaxFRC was 43%. A large scatter of baseline values was found for all indices with the exception of TTA. There was no correlation between TTA and age, length, or VmaxFRC. The IAI and EAI with the RC band in the upper position were the most sensitive indices, both within subjects (65% of the subjects had a significant change in IAI and 80% in EAI) and for the group as a whole (median values increased for IAI, P = 0.007, and for EAI, P = 0.017). TTA and phi were less sensitive, and a great discrepancy was observed between the two measurements. Poor results were obtained with the RC band in the lower position. No correlations were found between the changes in IAI and EAI, with the RC band around the lower chest and VmaxFRC. We conclude that IAI and EAI, measured with the RC band in the upper position and another band around the abdomen, can detect changes in thoracoabdominal asynchrony in most infants. The usefulness of assessing IAI and EAI in infants with acute lower airway obstruction needs to be determined.
Increased airway reactivity has been found in family members of school age children and adults with asthma. As the relation between recurrent wheeze in infancy and bronchial reactivity is not yet clear, it was decided to test bronchial reactivity to methacholine in both parents of 50 preschool age children with recurrent wheeze and in 200 population based controls matched for sex, age, smoking habits, and atopy. Wheezy children fulfilled the following criteria: first attack of wheezing before the age of 2 years, at least four wheezing episodes triggered by a respiratory infection, negative skin prick tests, and no symptoms related to allergy. Four parents and five controls did not undergo the methacholine challenge because their forced expiratory volume in one second was < 80% of the predicted value. Methacholine reactivity was not significantly different in parents and controls. In summary, an increased bronchial responsiveness was not found in parents of infants and young children with recurrent wheeze triggered by infection.
The Hering-Breuer reflex (HBR) plays an important role in the regulation of respiratory timing in infancy. Some investigators have noted that HBR is stronger when the respiratory rate (RR) is faster. However, this finding may be due to a spurious correlation, since one of the variables (expiratory time) used to calculate both HBR and RR is the same. We investigated this hypothesis with Monte Carlo (simulation) studies by using uncorrelated random numbers to calculate RR and HBR and found a strong spurious correlation (r = 0.7) between HBR and RR, i.e., subjects with higher RR had a stronger HBR. These results were confirmed algebraically, and the formula for the expected value of the correlation coefficient [E(r)] was derived. E(r) was always >0; it was 0.707 when no prolongation of inspiration occurred and was larger in the presence of a prolongation; when HBR strength was 100%, E(r) = 0.89, and when it was 200%, E(r) = 0.94. The expected value of the slope of the regression line of HBR on RR was found to be directly proportional to expiratory time during occlusion. As faster RRs produce stronger HBRs, any variable associated with RR, i.e., age, length, and weight, may influence HBR. This can lead to inconclusive or biased results in studies of the maturation of HBR with age and can confound comparisons across groups that do not have the same RR.
BACKGROUND: Raised respiratory rate is a useful sign to diagnose lower respiratory infections in childhood. However, the normal range for respiratory rate has not been defined in a proper, large sample. OBJECTIVE: To assess the respiratory rate in a large number of infants and young children in order to construct percentile curves by age; to determine the repeatability to the assessment using a stethoscope and compare it with observation. METHODS: Respiratory rate was recorded for 1 minute with a stethoscope in 618 infants and children, aged 15 days to 3 years old, without respiratory infections or any other severe disease when awake and calm and when asleep. In 50 subjects we compared respiratory rate taken 30 to 60 minutes apart to assess repeatability, and in 50 others we compared simultaneous counts obtained by stethoscope versus observation. RESULTS: Repeatability was good as the standard deviation of differences was 2.5 breaths/minute in awake and 1.7 breaths/minute in asleep children. Respiratory rate obtained with a stethoscope was systematically higher than that obtained by observation (mean difference 2.6 breaths/minute in awake and 1.8 breaths/minute in asleep children; P = .015 and P < .001, respectively). A decrease in respiratory rate with age was seen for both states, and it was faster in the first few months of life when also a greater dispersion of values was observed. A second degree polynomial curve accurately fitted the data. Reference percentile values were developed from these data. CONCLUSIONS: The repeatability of respiratory rate measured with a stethoscope was good. Percentile curves would be particularly helpful in the first months of life when the decline in respiratory rate is very rapid and prevents to use cut off values for defining "normality."
Only scanty data are available on the susceptibility of Haemophilus influenzae in Italy. The in vitro activity of ampicillin, ampicillin-sulbactam, cefaclor, cefuroxime, cefotaxime, chloramphenicol, erythromycin and trimethoprim-sulfamethoxazole against 327 strains of Haemophilus influenzae (55 encapsulated, 272 non-typeable) isolated from adults and children in northern Italy, between January 1984 and December 1989, was compared. Patients were affected by meningitis or other invasive infections, conjunctivitis, otitis, sinusitis, pneumonia or bronchitis. Minimal inhibiting concentrations were determined by a microdilution technique in Mueller Hinton broth supplemented with 10 microliters/ml NAD and 2-5% lysed horse blood. A concentration of 1 x 10(5) to 5 x 10(5) CFU/ml was used as the inoculum. The antibiotics were tested at concentrations ranging from 0.03 to 64 microliters/ml with the exception of trimethoprim-sulfamethoxazole, for which the range of concentrations examined were 0.01/0.25 to 32/512 microliters/ml. All the strains tested were susceptible to ampicillin-sulbactam, cefuroxime and cefotaxime, and more than 95% were susceptible to ampicillin, cefaclor and chloramphenicol. Only 4% were susceptible to erythromycin but most minimal inhibiting concentrations fell into the intermediate category. Strains isolated from adults were more susceptible to trimethoprim-sulfamethoxazole than strains isolated from children (85% vs 66%; p = 0.011).
Concentrations of interleukin 6 (IL-6) in cerebrospinal fluid (CSF) and serum of infants and children with bacterial meningitis were determined and correlations were sought with other indices of inflammation and with outcome. Forty-two patients ages 1 month to 15 years (mean, 2.5 years) were studied. IL-6 activity was detectable (greater than 50 units/ml) in 30 of 36 CSF samples collected at admission from patients with meningitis and in 1 of 23 controls with fever and normal CSF findings. Mean values were 36,000 units/ml (range, 151-156,000). IL-6 activity in CSF persisted during the first 5 days of illness. IL-6 concentrations at admission were not associated with clinical findings, CSF leukocyte, protein and glucose concentrations, serum C-reactive protein concentration and neurologic complications or sequelae. IL-6 was also detected in the serum of 3 of 14 patients with meningitis and in 0 of 7 controls with no infectious disease. The presence of IL-6 was not associated with bacteremia or with duration of fever before admission. The presence of IL-6 in the CSF of pediatric patients with bacterial meningitis is in accordance with available data on other cytokines and suggests their role as mediators of meningeal inflammation.
Data on susceptibility of Haemophilus influenzae are scanty in Italy. We compared the activity of loracarbef (Ly 163892), a new carbacephem, with that of 4 other agents against 265 strains of H. influenzae (46 type b, 219 nontypable) isolated from adults and children at Istituti Clinici di Perfezionamento of Milano, between 1/1/84 and 1/1/89, and also from 7 children at pediatric departments in Lombardy during 1988. In adults 72 strains were all isolated from sputum of patients with pneumonia or chronic bronchitis; in children 199 strains were isolated from conjunctiva (53% of the patients had also a concomitant respiratory infection), 24 from middle ear, 18 from sputum and 32 from blood or cerebrospinal fluid. Minimal inhibiting concentrations (MIC) were determined by the broth microdilution technique. The incidence of resistance of H. influenzae to ampicillin was 3.8%; the lowest percentage of resistance was found for loracarbef (0%) and the highest for erythromycin (94% for strains isolated from children and 97% for strains isolated from adults).
A commercial latex agglutination (LA) kit (Wellcogen, Wellcome Diagnostics) used to detect bacterial polysaccharide antigens (Haemophilus influenzae type b and Streptococcus pneumoniae) was compared with a modified counterimmunoelectrophoresis technique and blood culture for etiologic diagnosis of presumptive bacterial pneumonia requiring hospitalization in 60 infants and children. Serum, urine and either sputum or nasopharyngeal secretions were collected during the first 5 days of therapy for antigen detection. Blood culture was positive in 6 of 52 (11.5%) of cases. Antigens were detected by counterimmunoelectrophoresis and/or LA in 13 of 60 (21.7%) serum samples, 2 of 16 (12.5%) unconcentrated urine samples, 19 of 42 (45.2%) urine samples concentrated 25-fold and 21 of 45 (46.7%) sputum or nasopharyngeal secretions. Antibiotic treatment for 5 days did not affect the antigen detection rate. Counter-immunoelectrophoresis was more sensitive than LA in serum and urine but not in sputum. However, because false positive reactions were frequently obtained with LA on nasopharyngeal secretions of an age-matched control group, this test appears unreliable.
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Aztreonam was administered to 30 patients, ages 0.03 to 15.4 years, with severe and in 21 cases complicated urinary tract infections caused by members of the family Enterobacteriaceae and Pseudomonas aeruginosa which were resistant to ampicillin and susceptible to the study drug in vitro. A mean dose of 47.7 mg/kg was given intramuscularly every 12 h to 26 patients. In four patients with renal insufficiency, the dose was reduced according to pharmacokinetic data. Permanent urine sterilization and clinical cure were achieved in 22 patients, 13 of whom had urological malformations. In two patients with P. aeruginosa and Proteus mirabilis infections, the treatment failed. Another patient had an Escherichia coli reinfection 21 days after the end of therapy. Four patients with various urological abnormalities had gram-positive superinfections, and two patients had gram-negative superinfections during and at the end of therapy: all six had indwelling ureteric splints or pyelostomy as predisposing conditions. No adverse clinical effects were observed. Some transient and slight or moderate alterations were observed at the end of treatment: eosinophilia (nine cases), elevation of hepatic enzymes (eight cases), prolongation of prothrombin time (three cases), and neutropenia (one case). A pharmacokinetic study was performed in six patients with normal renal function and in seven patients with various degrees of renal insufficiency. The elimination half-life of the drug was inversely correlated with the glomerular filtration rate. At the dosage used, aztreonam proved effective for severe urinary tract infections caused by members of the family Enterobacteriaceae in pediatric patients.
Fifteen pediatric patients with complicated urinary tract infections due to Pseudomonas spp. were treated for 10 to 18.5 days with ceftazidime administered intramuscularly twice daily. Urine sterilization during therapy was obtained in all patients. Three patients had relapses which were cured with a second course of ceftazidime. Minor liver damage, eosinophilia, and Candida superinfection developed in one patient each.
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The purpose of this study was to analyze the role of gestational and postnatal age and of clinical conditions [e.g., respiratory distress syndrome (RDS)] on serum concentrations of amikacin in neonates treated according to commonly recommended dose schedules. Thirty-nine neonates (28.5-42 weeks of gestational age) were treated with the aminoglycoside at a mean dose of 7.2 mg/kg every 12 h for an average period of 6.5 days, and serum levels were monitored throughout treatment. Both gestational and postnatal age influenced amikacin levels. During the first days of life the presence of RDS was found to be strongly associated with amikacin accumulation. Neonates with retarded intrauterine growth according to their gestational age tended to have lower amikacin trough levels in the first days of life. No correlation was found between amikacin serum levels and hematocrit. Peak concentrations of the drug did not correlate with vital or clinical data, probably because of the variability in drug absorption from the intramuscular injection site. These data are discussed in light of the development of renal function and changes in body fluid compartments occurring in the preterm and term neonates during the first weeks of life.
The effect of intrauterine maturation on amikacin disposition was studied in 29 preterm and term neonates. Mean gestational age (weeks) of the patients was 34.5 +/- 3.3 S.D. and their birth weight 1.980 +/- 920 g. After the last administration of the drug, amikacin decay was measured in plasma and urine for 100-250 h. The serum concentration versus time profiles were fitted by nonlinear regression analysis. The parameters of a 2- or 3-compartment model with elimination from the central compartment were calculated. Initial elimination T 1/2, volume of the central compartment, and steady state volume of distribution were significantly related to intrauterine maturation (respectively r = -0.76; -0.63; -0.57) whereas no significant linear correlation was found between clearance and gestational age (r = 0.19). Patients with gestational age less than 34 wk had a significantly reduced clearance when compared with the neonates with gestational age greater than 36 wk (0.78 +/- 0.17 versus 1.0 +/- 0.4 ml/h/kg, P less than 0.05). The ratio between the volumes of distribution showed that a higher amount of amikacin penetrates the peripheral compartments with increased gestational age. The renal clearance calculated in six patients averaged 66% of the total body clearance, suggesting that elimination of the drug can occur in the neonate via nonrenal routes. Analysis of the long term urinary elimination of amikacin showed that about 5% of the total amount of the drug administered in 5-8 days of treatment is retained in the organism. Although quantitatively small, this amount is relevant for the potential nephrotoxicity of the drug.
35 neonates (mean gestational age: 34.9 +/- (SD) 3.5 weeks; mean birth weight: 2,180 +/- 890 g) treated with amikacin were examined for possible ototoxicity and nephrotoxicity. Audiometric tests were performed at 14.2-30.0 months postconceptional age by cross-checking behavioural with brain stem-evoked response audiometry. Only 1 infant was found with a mild hearing loss with brain stem audiometry, which, however, could not be attributed to amikacin with certainty. The effect of the aminoglycoside on the kidney was studied both by monitoring serum creatinine and the urinary elimination of the lysosomal enzyme N-acetylglucosaminidase (NAG). No significant difference was found in serum creatinine between the group under investigation and a control group of untreated premature neonates. A transient elevation was found in NAG urinary excretion in the neonates treated with amikacin. These results lead to the conclusion that amikacin at the recommended dosages (7.5 mg/kg every 12 h) causes a subclinical and reversible tubular damage in the neonate despite the high serum concentrations of the drug. The clinical relevance of this finding is discussed.