Reliability of salivary theophylline in monitoring the treatment for apnoea of prematurity.

OBJECTIVE: To evaluate the reliability of salivary levels of theophylline in monitoring therapy of apnoea of prematurity. STUDY DESIGN: Aminophylline was administered intravenously in 13 infants with apnoea, in a loading dose of 5 mg/kg and maintenance dose of 3 mg/kg, every 8 h. The patients were divided into two groups according to their postconceptional age (PCA): group A, of infants with small PCA (32.8+/-2.0 weeks; n=6 cases), and group B, infants with higher PCA (37.1+/-0.8 weeks; n=7 cases). RESULTS: A total of 57 paired samples of serum and saliva were obtained in all 13 infants. The mean serum level of theophylline was 7.8+/-5.8 microg/ml and the ratio between serum and salivary concentration of theophylline was 1.53+/-0.28. A strong correlation between the serum and salivary concentration of theophylline (r=0.973) was found. Infants with small PCA had significant higher serum concentration of theophylline than those with higher PCA (10.6 vs 5.3 microg/ml; P=0.0002). The difference between the mean ratios of serum/salivary theophylline levels in the two groups was low (1.44 vs 1.62; P=0.0155). CONCLUSION: The strong correlation of theophylline in serum and in saliva recommends the salivary levels as a reliable method for monitoring the treatment of apnoea of prematurity.

[Evaluation of the effect of inhaled glucocorticosteroids by morning cortisolemia]. / Evaluarea efectului glucocorticoizilor administrati inhalator prin cortizolemia matinala.

The authors study the effect on adrenal function of a small dose of inhaled steroids in children with asthma. The study group consisting in 61 children treated with inhaled steroids (38 children treated with beclomethasone dipropionate and 23 treated with fluticasone propionate) who were compared with 17 controls (children with asthma treated with nonsteroidal therapy). In the study group, after 12 months of therapy morning cortisolemia was lower as compared with the values before the treatment. In children treated with beclomethasone the morning cortisol before therapy was 217.6 +/- 76.4 nmol/L and after therapy of 171.5 +/- 52 nmol/L (p < 0.077). In children treated with fluticasone initial cortisol was of 210.8 +/- 19.5 nmol/L and after treatment of 175.2 +/- 30.9 nmol/L (p < 0.027).

[Evaluation of quality of life in children with bronchial asthma]. / Evaluarea calitatii vietii la copilul cu astm bronsic.

Asthma affects children physically, psychologically and socially. The quality of life is a subjective parameter that evaluates the impact of asthma on daily life of the child. The authors evaluated the evolution of the quality of life score in children with persistent asthma treated with controllers, during one year, and the correlation between the quality of life score and pulmonary function parameters. The evaluation of the quality of life was based on a questionnaire with 23 items (PA QLQ), which was applied on 64 children with asthma. The quality of life score was evaluated initially and every 3 months. Pulmonary function tests were measured by spirometry every 3 months and children recorded PEF twice daily At the end of the study the authors revealed the improvement of the quality of life score in 87% of children. Initially the value of the general score of quality of life was of 4.78 +/- 1.09 and it increased up to 6.53 +/- 0.56 (p = 0.0001) after 12 months. We noticed significant improvement of the scores for symptoms, activities and emotions, and also of circadian variation of PEF (p = 0.002). We revealed a relatively poor reverse correlation between general score of the quality of life and circadian variation of PEF (r = - 0.330). In conclusion, the evaluation of quality of life might appreciate the clinical course of asthma patients. Based on this results the authors suggest the use of the evaluation of the quality of life as a complementary method to the classical methods used for asthma monitoring in children.

A pharmacokinetic interaction study between omeprazole and the H2-receptor antagonist ranitidine.

The effect of ranitidine pretreatment on the pharmacokinetics of omeprazole was investigated in 14 male human volunteers. Omeprazole (40 mg, gastroresistant pellets) was administered to the volunteers in a two-treatment study design, either alone or after 5 days pretreatment with b.i.d. doses of 150 mg ranitidine. Plasma concentrations of omeprazole were determined over a 24-hour period following drug administration, by a validated RP-HPLC method. Pharmacokinetic parameters were calculated with compartmental and non-compartmental analysis, using the computer program Kinetica (Inna Phase). In the two periods of treatments, the mean peak plasma concentrations Cmax were 730.8 ng/ml for omeprazole alone and 802.1 ng/ml for omeprazole co-administered with ranitidine (not significant). The time taken to reach the peak, Tmax, was 1.29 h and 1.42 h, respectively (not significant). The areas under the curve (AUC0-10) were 1,453.3 ng.h/ml and 1,736.8 ng.h/ml for the two periods of treatment; thus a greater AUC was obtained after pretreatment with multiple doses of ranitidine. Our data show that the pharmacokinetics of omeprazole might be inhibited by pretreatment with ranitidine; however, the clinical relevance of this interaction still has to be confirmed.

[Increase of the prevalence of bronchial asthma and related symptoms in students in Cluj-Napoca. Epidemiologic study with a five-years interval]. / Cresterea prevalentei astmului bronsic si simptomelor asociate la scolarul mare în Cluj-napoca. Studiu epidemiologic la 5 ani interval.

BACKGROUND: The prevalence of asthma is increasing in developed countries during the past decade. In Romania there are few studies on asthma epidemiology and no data on the trend of the prevalence. AIMS: The authors investigate the prevalence of asthma and associated symptoms in children and evaluate the trend of prevalence 5 years apart. METHODS: We used a core questionnaire designed by the International Study of Asthma and Allergy in Children (ISAAC). The questionnaire was applied during 1995 in 2,866 children aged 13-14 years from a Romanian city, and during 2001 in 1,657 children from the same area. RESULTS: The prevalence of previous diagnosed asthma increased significant, from 3.3% in 1995 to 5.5% in 2001 (p = 0.0005). A higher percentage of pupils presented probable asthma (4.3% in 1995 and 13.6% in 2001; p < 0. 00001). Similar results were obtained regarding symptoms related to asthma like wheezing, cough during exercise and night cough. Previous diagnosed asthma was more frequent in boys, but probable asthma and symptoms related to asthma were more prevalent in girls both in 1995 and in 2001. The prevalence of asthma is similar with that reported in other central and eastern European countries that used the same core questionnaire provided by ISAAC. CONCLUSION: The prevalence of asthma and associated symptoms increased significantly during the past 5 years.

[The effects of long-term inhaled glucocorticoids on children's bones]. / Efectele glucocorticoizilor administrati de durata, pe cale inhalatorie, la copil, asupra osului.

The authors study, by calcanean ultrasonographic method, the effects of inhaled steroids, administered for long term, on the bone status, in children with persistent asthma. The study group consisted in 33 children with persistent asthma, treated for 12 months with low or moderate doses of either beclomethasone dipropionate or fluticasone propionate. In all of them there were measured the main ultrasonographic parameters, before and after treatment. The results were compared with those recorded in a control group. The control group consisted in 16 children with asthma that did not receive long term inhaled steroids. In the study group the were no statistically significant differences between ultrasonographic parameters measured before and after steroids inhaled treatment. There were no statistically significant differences between ultrasonographic parameters measured after steroid treatment in the study group and the same parameters recorded in the control group. The results of our study reveal that long term inhaled steroids therapy do not influence the bone density at the calcanean level.

[Prevalence of bronchial asthma in 7 years -old children in Cluj-Napoca, an ISAAC study]. / Prevalenta astmului bronsic la copiii de 7 ani din municipiul Cluj-Napoca. Studiu ISAAC.

The authors studied the prevalence of asthma in children of 7 years from Cluj Napoca and analyzed the possible risk factors. We used the questionnaire elaborated by International Study on Asthma and Allergic Diseases in Children (ISAAC) which allowed the comparison of our data with those from other countries. Anamnesis, functional tests and allergic skin tests were performed in children with positive answers for questionnaire. 1334 children completed the study, 52.5% being males. Prevalence of asthma diagnosed previous to the questionnaire was of 5.7%, and it was higher in males (6.1%). By anamnesis, functional and skin tests data the diagnosis of asthma was made in a total of 217 children, so that the real prevalence of asthma is of 16.3% in this age group. Maternal smoking during the first year of life was significantly higher in children with wheezing. The high number of respiratory tract infections in the first year of life could also play a role. In conclusion, prevalence of asthma diagnosed in children of 7 years of age from Cluj Napoca is of 5.7% with a real prevalence of disease that seems to be much higher, of 16.3%. Maternal smoking represents a risk factor correlated with wheezing.

[Respiratory resistance measured by interrupter technique in asthmatic children. Correlation with spirometry]. / Masurarea rezistentei respiratorii prin metoda întreruperii fluxului la copiii cu astm bronsic. Corelatii cu spirometria.

Respiratory resistance measured by the interrupter technique (Rocc) is very attractive in young children because minimal comprehension and coordination are needed. It is feasible in children below 5 years of age, in children with acute asthma and the device is simple, small sized, and relatively cheap. The objective of this study was to determine the correlation between Rocc and spirometry in co-operative children with asthma. We studied patients with asthma old enough to perform spirometry. The spirometric parameters evaluated were forced vital capacity (FVC), forced expiratory flow in 1 second (FEV1), peak expiratory flow (PEF), and maximal expiratory flow at 50% of vital capacity (MEF50). Respiratory resistance was measured during normal breathing, with a nose clip, with the neck in slight extension. The maneuver was repeated until 5 relatively constants values were obtained. The mean value was evaluated. We analyzed the results by the Pearson correlation quotient. Thirty-four children were tested (20 boys) with a mead age of 8,91 years (limits: 4-18 years), a mean height of 135.88 cm (106-173 cm), a mean weight of 33.95 kg (17-66 kg). Rocc correlated well with FVC (r = -0.81; p < 0.05), with FEV1 (r = -0.79; p < 0.05), with PEF (r = -0.76; p < 0.05), and with MEF50 (r = -0.76; p < 0.05). In conclusion, Rocc values correlated well with the main spirometric parameters, and this method (Rocc) could be used as a substitute of spirometry in young children, who cannot perform forced expiratory maneuvers.

[The prevalence of bronchial asthma in 13- to 14-year-old schoolchildren in the city of Bistrita]. / Prevalenta astmului bronsic la elevii de 13--14 ani din municipiul Bistrita.

Asthma is a major worldwide public health problem, with a prevalence in children which varies in different geographical areas from 0 to 30%. The true prevalence of the disease is not known exactly due to the lack of consensus of its definition and because the different methods used by the studies for obtaining epidemiological data. The authors study the prevalence of asthma among schoolchildren aged 13-14 years, from Bistrita, using the ISAAC standardised methodology, world-wide accepted. A total number of 889 schoolchildren aged 13-14 years from local schools, were enrolled in the study, the sample representing 63.67% of all 1396 schoolchildren of the same age registered in the 1996/1997 school year in Bistrita. The first step consisted of completing a questionnaire about asthma, allergic rhinitis and eczema. Seventy-five (8.43%) schoolchildren gave positive response to asthma and asthma associated symptoms, with a prevalence of 7.43% in boys (33 from the total of 444) and 9.43% in girls (42 of 445). In the second step 61 schoolchildren of those who gave positive responses to the questionnaires about asthma-wheezing, representing 81.33% of the total number of 75, were complex examined (history and physical examination, respiratory function and allergological tests). The following results were obtained by correlation of questionnaires and complex examinations: 17 subjects known with asthma before completing the questionnaire, 1 with probable asthma and 21 with certain asthma. Those 39 children represent 4.38% of the total number of schoolchildren who had been examined, with a gender rate of 19 boys (4.27%) and 20 girls (4.49%). In conclusion, the estimated asthma prevalence among 13-14 years old schoolchildren from Bistrita is 4.38%, with a similar gender rate. The prevalence data found for 13-14 years old schoolchildren in Bistrita are comparable to those made in other geographical areas in Romania, and to those reported by former socialist countries from Eastern Europe.

[The monitoring of delayed-release theophylline therapy in bronchial asthma in children by determining the salivary concentration]. / Monitorizarea terapiei cu teofilina cu eliberare întârziata în astmul bronsic la copil prin determinarea concentratiei salivare.

Long-term therapy with slow-release theophylline is compulsory to be monitorized by measuring serum concentration of the drug. This is due to the narrow therapeutically index of theophylline for monitoring the long term therapy with this drug, and to establish the correlation between the serum and saliva concentration of theophylline. The study group was represented by 13 children with asthma, with the age between 2 and 13 years that received theophylline in an average dosage of 15.2 mg/kg/24 hours. In all of them there were obtained two paired simultaneous samples of venous blood and of saliva, at 4 hours and at 8 hours respectively, after the administration of theophylline. For facilitate the saliva sampling, its production was stimulated by applying citric acid on the tongue and aspiration with a sterile syringe. For measuring the serum and saliva levels of the drug it was used mass spectrometry with 15N-theophylline as internal standard. Serum theophylline concentration varied between 6.56 +/- 4.48 micrograms/ml at 8 hours after drug administration and respectively 7.45 +/- 3.94 micrograms/ml at 4 hours after drug administration. Saliva concentrations of theophylline varied between 4.18 +/- 2.40 micrograms/ml at 8 hours after drug administration and respectively 4.66 +/- 2.39 micrograms/ml at 4 hours after drug administration. The average ratio between serum and saliva concentration in the 24 paired samples was 1.62 +/- 0.18. The intraindividual variation of this ratio was 8.64%.

[The evaluation parameters of the long-term treatment efficacy of theophylline in the child with bronchial asthma]. / Parametrii de evaluare a eficientei tratamentului de durata cu teofilina la copilul cu astm bronsic.

In the past decade the use of theophylline was less extensive because of its narrow therapeutically index and due to its side effects. The widening of possibilities of monitoring the treatment by serum level determination, the introduction of slow release formula, and the demonstration of antiinflammatory effects made theophylline to become actual again. Theophylline is indicated for the chronic treatment of asthma in association with other medication. The authors study the efficacy and serum level of theophylline in 13 children with asthma who received slow release theophylline in a dosage of 15.2 mg/body weight/24 hours in average, administered 3 times a day. The efficacy was estimated by a clinical score and the serum level was determined by isotopic mass spectrometry with 15N-theophylline as internal standard. After a period of at least 2 months of therapy it was recorded the amelioration of clinical score (with 5.09 points, that represents 36.3% of the maximum initial score) and the reducing of circadian variation of peak expiratory flow from 27% to 15%. The serum level of theophylline was of 8.25 +/- 4.16 micrograms/ml at 4 hours after administration and of 5.69 +/- 2.6 micrograms/ml at 8 hours after administration of the last dose. The individual values less than 5 micrograms/ml was found in 3 of 13 children at 4 hours and in 7 of 13 children at 8 hours after the last dose. There were no patients with toxic serum levels of theophylline (> 20 micrograms/ml). The correlation between serum level of theophylline and the dosage was weak both at 4 hours (r = 0.054) and 8 hours (r = 0.229) after the last dose. At the same dose there were found high interindividual variations. These findings are arguments for the usefulness of determination of serum levels of theophylline, that together with clinical and functional parameters allowed the individualization of the dosage.

Early re-feeding in the management of acute diarrhoea in infants of 0-1 year of age.

We compared early versus late re-feeding in the management of acute diarrhoea in the first year of life. In the study group (73 groups) breast feeding was resumed or early re-feeding was performed in non-breast-fed infants, so that the feeding regimen used prior to the onset of the disease was reached within 2-3 days. In the control group (49 patients) late re-feeding was performed so that the infants returned to their original feeding pattern after 4-6 days. there were no significant differences between the two groups in the number of stools and stool output per day, or in the duration of the disease. No weight gain or loss during the diet was noted more frequently in the late re-feeding group (67.2% versus 2.3.4%). This study confirms the favourable effect on body weight of early re-feeding in the management of acute diarrhoea.

Lupus anticoagulant and transient severe bleeding tendency in a girl aged nine years.

A 9-year old girl admitted in our clinic for severe hemorrhagic syndrome was found to display a high level of lupus anticoagulant (LA) leading to an important prolongation of phospholipid-dependent coagulation. Positive antinuclear and anti DNA antibodies, as well as very low levels of complement C3 and C4 proteins confirmed the diagnosis of systemic lupus erythematosus. Therapy with cortisone and cyclophosphamide led to normalization of the clotting tests but could not arrest the development of renal and hepatic lesions. The patient is one of the few cases with presence of lupus anticoagulant associated with severe hemorrhagic diathesis, in opposition to the more frequently reported thrombotic tendency connected with antiphospholipid antibodies.

Plasma fibronectin and factor XIII in nephrotic syndrome.

When compared to control subjects plasma fibronectin and factor XIII as well as plasma fibrinogen, factor VIII-related antigen and serum cholinesterase were found to be significantly increased in nephrotic patients. Factor XIII activity was positively correlated with serum cholinesterase, while plasma fibronectin displayed weak correlations with plasma fibrinogen and factor VIII-related antigen. It is considered that increased levels of factor XIII and fibronectin should be related to the intensity of the liver's compensative response to proteinuria, although their turnover rates and the signals triggering this response may differ. It is however difficult to assess possible consequences of the above-mentioned changes for the evolution of the nephrotic syndrome.

C5b-9 deposition in children with glomerular diseases.

Kidney biopsies were obtained in 28 children with glomerular diseases and studied using indirect immunofluoreoscence and immunoperoxidase for the detection of IgG, IgA, IgM, Clq, C3c, C4, Fibrinogen and the neoantigens of the terminal C5b-9 complement complex. An affinity-purified rabbit IgG was used to recognize the neoantigens of the assembled terminal components of the complement system into the C5b-9 complex. The immunohistochemical studies were correlated to the clinical data and laboratory investigations. Fourteen of the 28 patients presented specific C5b-9 glomerular deposits; they were also present at the tubular sites in 8 patients and at the vascular sites in 12 patients. An unfavourable evolution was observed for patients presenting C5b-9 deposits in contrast to those without such deposits, even of the same histopathological pattern of glomerulonephritis. The presence of C5b-9 complex at the site of glomerular injury suggests a pathological involvement of the "in situ" complement activation and could be a marker in the prognosis of the glomerular diseases.

Immunohistochemical detection of the terminal C5b-9 complement complex in children with glomerular diseases.

Kidney biopsies were obtained in 28 children with glomerular diseases and studied using indirect immunofluorescence and immunoperoxidase for IgG, IgA, IgM, C1q, C3c, C4, fibrinogen and the neoantigens of the terminal C5b-9 complement complex. C5b-9 deposits were detected in glomeruli of 14, in tubules of eight and in vessels of 12 cases. Patients with C5b-9 deposits fared worse than those without such deposits, even with the same histopathological type of glomerulonephritis. The C5b-9 complex suggests an in situ complement activation.