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Biomedical subjects

P Scheinmann

Publications and source records attributed to P Scheinmann.

At least 91 records · Page 5Linked to original sources

Correlation between activity of beta-lactam agents in vitro and bacteriological outcome in acute pulmonary exacerbations of cystic fibrosis.

A study was conducted to determine whether a direct relationship exists between beta-lactam and/or aminoglycoside activity measured in vitro and bacteriological outcome in acute pulmonary exacerbations of cystic fibrosis. Twenty-seven patients, aged between 6 months and 24 years (mean age 10 1/2 years), were included in the study and received 41 i.v. courses of a beta-lactam agent combined with an aminoglycoside. A total of 63 Pseudomonas aeruginosa strains were found in sputum taken on admission at densities exceeding 10(6) cfu/g of sputum. For each episode, the serum inhibitory quotient (SIQ) and the serum bactericidal quotient (SBQ) of the beta-lactam agent and of the aminoglycoside administered were determined for the Pseudomonas aeruginosa isolate(s). The SIQs and SBQs were calculated by dividing the average peak serum levels achievable in the patients by the minimal inhibitory concentrations and minimal bactericidal concentrations, respectively. The SIQs and SBQs were compared to bacteriological outcome. Bacteriological success was defined as a decrease of 2 log10 counts or more in the Pseudomonas aeruginosa density in sputum between days 0 and 7 of therapy. The SIQ and SBQ of beta-lactam agents were good predictors of bacteriological outcome: SIQs of < 1:16 were 100% predictive of failure (chi 2 28; p < 0.001) and of > or = 1:64 were 92.9% predictive of success (chi 2 35.68; p < 0.001); SBQs of < 1:8 were 100% predictive of failure (chi 2 42.78; p < 0.001) and of > or = 1:32 were 95.8% predictive of success (chi 2 31.5; p < 0.001). Aminoglycoside SIQs and SBQs were not predictive of outcome.

Adolescent↗

Use of polymerase chain reaction for improved diagnosis of tuberculosis in children.

OBJECTIVE: To study the value of a rapid diagnostic method based on the amplification by polymerase chain reaction (PCR) of a fragment of the IS6110 insertion element for the detection of Mycobacterium tuberculosis in children. DESIGN: We tested 199 specimens obtained from 68 children referred for evaluation of suspected tuberculosis. RESULTS: In 83.3% of children with active disease and 38.9% with tuberculous infection but no evidence of disease, at least one positive PCR result was observed. No child without tuberculosis had positive PCR results (100% specificity). The sensitivity of the PCR was increased by testing of multiple samples from the same child and use of Chelex particles (Bio-Rad Laboratories, Ivry, France) rather than guanidine isothiocyanate-silica particles for DNA extraction. Bronchoalveolar lavage samples were no more useful than gastric aspirates. CONCLUSIONS: If appropriate laboratory methods are used, DNA amplification is a reliable method for the early diagnosis of tuberculosis in children and appears to be very helpful in clinical pediatric practice when the diagnosis of active tuberculosis is difficult or needs to be rapidly confirmed.

Adolescent↗

Imbalance between 95 kDa type IV collagenase and tissue inhibitor of metalloproteinases in sputum of patients with cystic fibrosis.

A growing body of evidence suggests that neutrophil-derived proteinases play a major role in lung tissue damage in cystic fibrosis (CF). Most previous studies have focused on serine proteinases such as neutrophil elastase, providing no information on the extent to which metalloproteinases participate in proteolytic processes in CF. To address this issue, we evaluated the contribution of one of the major neutrophil metalloproteinases, i.e., 95 kDa gelatinase (type IV collagenase), to the total gelatinolytic activity measured in sputum specimens from 27 patients with CF. Compared with asthmatic children (n = 9), CF patients had a 6.7 times greater level of total gelatinase activity in sputum revealed by zymography. The 95 kDa gelatinase was increased 3.7-fold in the CF subjects (2,441 +/- 411 [SEM] arbitrary units [AU] x 10(6) per ml of sputum versus 665 +/- 201 in asthmatics) and the 88-kDa active form 23.2-fold (2,272 +/- 372 AU x 10(6) per ml of sputum versus 98 +/- 43, respectively). Using radiolabeled 3H-gelatin as the substrate, we demonstrated uninhibited gelatinolytic activity in all CF patients; this activity was significantly correlated to disease severity as assessed by pulmonary function tests. Western blotting using anti-tissue inhibitor of metalloproteinase (anti-TIMP) and anti-95/88-kDa gelatinase antibodies demonstrated a more than 10-fold excess of 95/88 kDa gelatinase over TIMP. Bacterial proteinases from Pseudomonas aeruginosa were shown to contribute little to the gelatinolytic activity measured in sputum supernatants from patients with CF, although culture supernatants from various P. aeruginosa strains expressed gelatinolytic activity in vitro. Finally, lung damage, as assessed by increased type IV collagen degradation products in sputum, was significantly correlated to concentrations of active 88 kDa gelatinase. These data argue for a significant role of 95/88 kDa gelatinase in airway damage in CF.

Adolescent↗

Enhanced arachidonic acid metabolism in alveolar macrophages from wheezy infants. Modulation by dexamethasone.

To test the hypothesis that alveolar macrophages (AM) from wheezy infants release increased amounts of eicosanoids, as do AM from adults with asthma, we compared eicosanoid release by unstimulated- and ionophore-A23187-stimulated AM from 13 wheezy and six nonwheezy infants and analyzed its regulation by dexamethasone in vitro. Alveolar macrophages from wheezy infants released greater amounts of thromboxane A2 (TxA2) and leukotriene B4 (LTB4) under resting conditions and of TxA2 upon stimulation than did those from control subjects. Dexamethasone induced a dose-dependent inhibition of the spontaneous and A23187-stimulated release of TxA2, but not of the A23187-stimulated release of lipoxygenase products. The inhibition of TxA2 formation was maintained when free arachidonic acid was added during A23187 stimulation, demonstrating that dexamethasone acted mainly at a postphospholipase A2 site. AM exposed to acetylsalicylate and then incubated overnight exhibited de novo cyclooxygenase synthesis, suggesting the presence of the inducible cyclooxygenase as a target for inhibition by dexamethasone. In conclusion, our findings suggest that AM from wheezy infants are activated in vivo to release eicosanoids, as are AM from asthmatic adults, and they support the therapeutic indications of glucocorticoids in severe recurrent wheezing of infancy.

Adult↗

Ability of new lung function tests to assess methacholine-induced airway obstruction in infants.

We assessed the ability of innovative lung function tests to detect bronchial obstruction induced by methacholine bronchial challenge. Fifty-five recurrently wheezy infants (mean age 16 +/- 5.2 months) free of respiratory symptoms underwent baseline lung function tests. Forty-two completed the methacholine challenge. Maximal flow at functional residual capacity (VmaxFRC) was obtained using the squeeze technique; compliance and resistance of the respiratory system (Crs, Rrs) was measured with the passive expiatory flow volume technique; tidal volume breathing patterns were analyzed from recordings of respiratory rate (RR), tidal volume (VT), and inspiratory time divided by total cycle of duration (Ti/Ttot). Expiratory tidal flow volume (V/VT) curves were described with multiple indices such as the ratio of expiratory time necessary to reach peak tidal expiratory flow (Fpet) to expiratory time (Tme/Te). Transcutaneous oxygen tension (PtCO2) was measured as an indicator of response to methacholine challenge. Of 42 infants 41 responded to methacholine by a change > or = 2 standard deviations from baseline values. The mean SD unit changes were 9.8 in PtCO2, 3.7 for VmaxFRC, 2.8 for Crs, 2.09 for Rrs, 3.1 for RR, 1.6 for Ti/Ttot, 2.2 for Tme/Te 3.9 for PFVt. We conclude that these noninvasive lung function tests, especially VmaxFRC and Fpet, can be used to detect minor or moderate airway obstruction. Further studies are needed to determine the value of the tests in assessing bronchial disease and effects of its treatment.

Airway Obstruction↗

Nonspecific refractoriness to adenylyl cyclase stimulation in alveolar macrophages from infants with recurrent bronchiolitis.

Epidemiologic studies suggest an association between recurrent bronchiolitis in children younger than 3 years of age and diagnosis of asthma later in life. Bronchoalveolar lavages from 20 infants with recurrent wheezing and 18 nonwheezy control subjects were analyzed to determine whether alveolar macrophages of wheezy infants present abnormalities similar to those described in adults with asthma. Alveolar macrophages from both groups responded in vitro, in a concentration-dependent manner, to prostaglandin E2, salbutamol, and forskolin, drugs that increase cyclic adenosine monophosphate levels. However, alveolar macrophages from infants with recurrent wheezing accumulated less cyclic adenosine monophosphate than those from control subjects in response to all three stimulations. These results are in agreement with the reduced cyclic adenosine monophosphate response to different agonists demonstrated in leukocytes from patients with asthma, and suggest that this refractoriness could be one of the precipitating events in the development of asthma observed in a large proportion of infants who have had bronchiolitis.

Adenylyl Cyclases↗

Sensitization to inhalant allergens in wheezing infants is predictive of the development of infantile asthma.

Early recognition of infantile asthma in wheezing infants is a major problem for physicians. We investigated whether detection of early sensitization to inhalant allergens would be useful to identify those wheezing infants who are likely to develop asthma. A total of 67 infants (aged 1-25 months) hospitalized for a wheezing episode were initially tested for reactivity to inhalant allergens by both skin prick test and in vitro measurement of specific IgE antibodies (Phadiatop). Thirty-seven of the infants were already considered to have infantile asthma, and 30 presented only their first or second wheezing episode when included in the study. All infants were followed for a mean period of 18 months. Seventeen (25%) infants, including seven infants initially not asthmatic, had positive prick test to Dermatophagoides pteronyssinus or to cat fur. All of these children were diagnosed as suffering from infantile asthma at the end of the follow-up. Thus, skin test positivity to inhalant allergens was significantly associated with the diagnosis of infantile asthma (P < 0.05) and could be considered to be predictive of the development of infantile asthma (P < 0.03). In contrast, Phadiatop was less sensitive than skin prick tests, and only five children had positive in vitro test results, suggesting that specific IgE may primarily bind to tissue mast cells before being detectable in serum. We concluded that sensitization to inhalant allergens may distinguish wheezing infants who develop asthma from those who do not, and that skin testing may assist the early diagnosis of asthma in wheezing infants.

Aging↗

Bronchopulmonary dysplasia: value of CT in identifying pulmonary sequelae.

OBJECTIVE: Pulmonary dysfunction is common in children who survive bronchopulmonary dysplasia. Chest radiographs are not satisfactory for the identification of the sequelae of bronchopulmonary dysplasia because, although they often show abnormalities, the abnormalities are usually minor and sometimes absent. We therefore assessed the value of CT for identifying the sequelae of bronchopulmonary dysplasia. MATERIALS AND METHODS: Twenty-three children (mean age, 4 years) who had survived neonatal bronchopulmonary dysplasia and had signs of chronic pulmonary dysfunction (recurrent episodes of coughing, wheezing, dyspnea, pneumonia, respiratory insufficiency) were examined with chest radiographs and high-resolution CT scans of the chest. Two reviewers qualitatively analyzed the chest radiographic and CT findings by describing the most consistently found lesions and their frequencies. RESULTS: The chest radiographs showed hyperexpansion in 17, hyperlucent areas in 11, and linear opacities in 10 of the 23 children. Pleural thickening was not observed, and four children had normal findings on chest radiographs. All 23 CT scans showed abnormalities, including multifocal areas of hyperaeration, well-defined linear opacities, and triangular subpleural opacities with an external base and an internal apex. In 20 of 23 children, all three abnormalities were present. For the three other children, two of these three abnormalities were found. No bronchiectasis was observed in any of the cases. CONCLUSION: Lesions in survivors of bronchopulmonary dysplasia with chronic pulmonary dysfunction are visualized better on CT scans than on chest radiographs. Importantly, CT findings of multifocal areas of hyperaeration, numerous linear opacities facing triangular subpleural opacities visible on several consecutive sections, and no bronchiectasis should suggest the presence of sequelae of bronchopulmonary dysplasia.

Bronchopulmonary Dysplasia↗

[Pneumothorax revealing pneumoblastoma in an infant].

BACKGROUND: Pulmonary blastoma is a tumor with bad prognosis that is exceptionally seen before the age of 2 years. CASE REPORT: A 3 1/2 month-old infant was admitted because she suffered from tachypnea. A left pneumothorax with shift of the mediastinum was recognized that required insertion of a chest tube followed by ventilation and pleural drainage. X rays and CT scan showed a round bullous lesion in the left lung that persisted at the age of 5 months. At that time, clinical deterioration led to thoracotomy allowing excision of a bullous tumor; histological examination showed that this tumor was a pulmonary blastoma. Recurrence of this tumor, 16 months later, required chemotherapy and surgical excision. The patient is normal at the age of 4 years. CONCLUSION: Pulmonary blastoma is exceptional in infancy; it may be revealed by pneumothorax. Its bad prognosis requires aggressive therapy.

Diagnosis, Differential↗

[Value of ipratropium bromide in asthma crisis in children].

Ipratropium bromide is a synthetic derivative of atropine with little absorption when used in inhalation, and therefore little secondary effects. The authors review its pharmacological properties and therapeutic efficacy in the treatment of asthma in children. Combined nebulized inhalation of ipratropium bromide and beta 2 sympathomimetic results in a more efficient and more sustained bronchodilatation than beta 2 sympathicomimetic alone in the treatment of acute asthma in children. Ipratropium bromide should be usefully introduced in the therapeutic scheme of acute asthma in children. Further studies will be necessary in order to determine its efficacy and tolerance in infants.

Adolescent↗

Molecular epidemiology of chronic pulmonary colonisation by Pseudomonas aeruginosa in cystic fibrosis.

The epidemiology of pulmonary colonisation by Pseudomonas aeruginosa was studied in 21 patients with cystic fibrosis (CF) by field inversion gel electrophoresis. DraI-DNA restriction patterns were analysed for 187 P. aeruginosa isolates from these patients. The results revealed that the strains present in individual patients varied during the course of chronic colonisation; the emergence of new strains often was associated with periods of antibiotic therapy. Patients often were colonised by more than one strain (two or three strains were present in 54% of the patients) and the strains obtained from unrelated patients were highly heterogeneous, in contrast to those isolated from a pair of twins. These results demonstrate the heterogeneity and variability of P. aeruginosa isolates in the pulmonary flora of chronically infected CF patients.

Adolescent↗

Computed tomography with normal chest radiograph in tuberculous infection.

Children with primary tuberculosis infection without disease must be identified and treated preventively to avoid an increase in the incidence of tuberculosis in children. However, the recognition of infected cases without disease is often difficult. In particular, minimal active disease may be present in many cases but unrecognised on chest radiography. Computed tomography was therefore performed in 15 children with tuberculous infection and a normal chest radiograph to measure the size of their mediastinal lymph nodes. Ten control children without tuberculosis were also evaluated. When compared with controls it was found that nine of 15 (60%) infected children had enlarged lymph nodes. Adenopathies were more frequent in infected children less than 4 years old than in those over 8 years old. The demonstration of unrecognised active disease in many infected children raises the question of the adequate treatment for these children. It is proposed that a two drug regimen would be more appropriate than isoniazid alone in these cases.

Adolescent↗

Value of ELISA using antigen 60 for the diagnosis of tuberculosis in children.

We evaluated the possible value of enzyme-linked immunosorbent assay (ELISA) using antigen 60 (A60) for improved diagnosis of tuberculosis in children. Results obtained in 31 children with active tuberculosis and in 16 patients with tuberculous infection without disease were compared with the results of 198 control subjects with no mycobacterial disease. In control children, anti-A60 IgG increased with age and the optical density (OD) in ELISA assays rose from .079 +/- .053 (OD +/- SD) in children younger than 5 years old to 0.146 +/- 0.082 OD in children older than 5 years. In control subjects younger than 2 years old, IgG OD values were significantly higher in BCG-vaccinated children than in nonvaccinated children. At a chosen specificity of 98 percent, a positive serodiagnosis was observed in 68 percent of children with clinically active tuberculosis. In these children with active disease, smears were positive in only 26 percent of cases and mycobacterial cultures yielded the organism in 45 percent of cases. None of the infected children without disease had high IgG OD values. IgM measurements were also evaluated. Mean values from control and diseased children overlapped, leading to a low sensitivity (19 percent) in children with clinically tuberculosis active. We conclude that anti-A60 IgG measurement is a rapid and low-cost technique that enhances the diagnosis of clinically active tuberculosis in children and may distinguish recent infection without disease from infection with disease.

Adolescent↗

Bronchiectasis in a child after acrolein inhalation.

Acrolein is an unsaturated aldehyde produced by combustion of many organic compounds. Massive exposure may lead to severe pulmonary disease and possibly death. We report a case of intoxication in a 2-year-old boy; an 18-month follow-up showed development of obstructive bronchiolar disease with diffuse bronchiectasis.

Accidents, Home↗

[Efficacy of a powder inhaler (Turbuhaler) in moderate asthmatic crises in children].

The use of a metered dose inhaler can be difficult in children, and requires the juxtaposition of an inhalation chamber. Powder inhalers offer different means of administration and are simpler to use and can be easily carried in the pocket or in a school satchel. The aim of this study is to assess the use of a beta-2-mimetic powder inhaler (Bricanyl Turbuhaler) in children presenting with an exacerbation of asthma. Thirty children aged from 4 to 14 years were included in an open random study in parallel groups. After a baseline measure of pulmonary function, the children inhaled 500 microgram of powdered terbutaline, or with metered dose aerosol attached to a spacer device (Nebuhaler). A significant bronchodilatation was apparent in the two groups of children which was measured at 15 and 30 minutes after the inhalation of the drug (measures of peak flow and forced expiratory volume in one second and of specific airways resistance were made). The bronchodilator response was similar whatever the method of inhalation. Although the inspiratory flow is decreased in an exacerbation this work shows that it is possible to advise the use of a powder inhaler in children presenting with a moderate exacerbation of asthma.

Acute Disease↗