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Biomedical subjects

F Brus

Publications and source records attributed to F Brus.

At least 19 recordsLinked to original sources
PubMed2006

[Accurate assessment of heart murmurs in children: thorough medical history and physical examination required].

4 children, boys aged 12, 5, 1.5 and 11 years, had a heart murmur. The 12-year-old boy could also not finish a football match and appeared to have atrioseptal defects (ASD). The 1.5-year-old boy had pulmonary symptoms that were not responsive to asthma medication; he also had ASD. The 11-year-old boy had had chest pain and pressure following exertion for 2 years; he appeared to have an aortic stenosis. Symptoms disappeared in all 3 patients after surgical correction. In the 5-year-old asymptomatic boy the murmur was deemed to be innocent following medical history and physical examination. Children frequently have heart murmurs. Most heart murmurs are innocent but some are caused by heart defects. Careful evaluation of the medical history and physical examination are critical in the differentiation of innocent and pathological heart murmurs. Routine supplementary diagnostic tests in children with heart murmurs are of limited value and are often misleading. One should inquire about specific and nonspecific symptoms and also perform systematic inspection, palpation and auscultation to identify any characteristics that suggest a heart murmur caused by a heart defect.

Aortic Valve Stenosis↗
PubMed2004

Seasonality of long term wheezing following respiratory syncytial virus lower respiratory tract infection.

BACKGROUND: It is well known that respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is associated with subsequent wheezing episodes, but the precise natural course of wheezing following RSV LRTI is not known. This study aimed to determine the continuous development of wheezing following RSV LRTI in children up to the age of 3 years. METHODS: A prospective cohort study was performed in 140 hospitalised infants with RSV LRTI. Continuous follow up data were obtained with a unique log in which parents noted daily respiratory symptoms. RESULTS: A marked decrease in wheezing was seen during the first year of follow up. The burden of wheezing following RSV LRTI was observed during the winter season. Signs of airflow limitation during RSV LRTI were strongly associated with wheezing during the follow up period. Total and specific serum immunoglobulin E levels, patient eczema, and parental history of atopy were not associated with wheezing. CONCLUSIONS: Airway morbidity following RSV LRTI has a seasonal pattern, which suggests that viral upper respiratory tract infections are the predominant trigger for wheezing following RSV LRTI. There is a significant decrease in airway symptoms during the first 12 months after admission to hospital. Simple clinical variables, but not allergic risk factors, can predict the development of wheezing following RSV LRTI.

Child, Preschool↗
PubMed2001

Local interferon-gamma levels during respiratory syncytial virus lower respiratory tract infection are associated with disease severity.

To investigate the role of cell-mediated immunity during respiratory syncytial virus (RSV) infection, interferon (IFN)-gamma and interleukin (IL)-10 levels in nasopharyngeal secretions were measured in infants with lower respiratory tract infection (LRTI) caused by RSV. A novel technique was used to measure in vivo cytokine levels in nasopharyngeal aspirates (NPAs). Cytokine levels in the NPAs of 17 mechanically ventilated infants and 43 nonventilated hospitalized infants were compared. As expected, mechanically ventilated infants were significantly younger than nonventilated infants (7 vs. 14 weeks). IFN-gamma levels were above the limit of detection in the NPAs of 3 (18%) mechanically ventilated infants and in the NPAs of 26 (60%) nonventilated infants. IL-10 levels in the NPAs of mechanically ventilated and nonventilated infants were comparable. It is hypothesized that maturation-related mechanisms have a key role in the development of RSV LRTI that results in mechanical ventilation.

Age Factors↗
PubMed2001

Airflow limitation during respiratory syncytial virus lower respiratory tract infection predicts recurrent wheezing.

BACKGROUND: Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is frequently followed by recurrent wheezing. Thus far no clinical risk factors have been identified to predict which infants will have wheezing episodes subsequent to RSV LRTI. OBJECTIVE: To determine clinical predictors for airway morbidity after RSV LRTI. METHODS: In a 1-year follow-up study we investigated the predictive value of auscultatory findings characteristic of airflow limitation (wheezing) during RSV LRTI for subsequent airway morbidity. Clinical characteristics, including the presence or absence of signs of airflow limitation, of hospitalized infants with RSV LRTI were prospectively recorded during 2 winter epidemics. During a 1-year follow-up period parents of 130 infants recorded daily airway symptoms. OUTCOME MEASURE: Recurrent wheezing defined as > or = 2 episodes of wheezing. RESULTS: Signs of airflow limitation during RSV LRTI were absent in 47 (36%) infants and present in 83 (64%) infants. Recurrent wheezing was recorded in 10 (21%) infants without signs of airflow limitation and in 51 (61%) with signs of airflow limitation during initial RSV LRTI (relative risk, 0.29, P < 0.001). In a multiple logistic regression model, airflow limitation during initial RSV LRTI proved independent from other clinical parameters, including age, parental history of asthma and smoke exposure. CONCLUSIONS: A sign of airflow limitation during RSV LRTI is the first useful clinical predictor for subsequent recurrent wheezing.

Auscultation↗
PubMed2000

[Septic arthritis in two young children caused by unusual gram-negative pathogens].

Two children, a girl aged 2 years and a boy aged 10 months, were moderately ill with signs of inflammation of the left and the right knee, respectively. Both had had pharyngitis, and the boy also had paronychia of the right foot. The Gram preparation of synovial fluid showed Gram-positive cocci in the girl, while Kingella kingae was cultured. In the boy, a Moraxella was cultured from the synovial fluid using an aerobic blood culture system. Both recovered without sequelae after adequate antibiotic treatment. The micro-organisms cultured were Gram-negative bacteria, which are rarely seen in septic arthritis and are difficult to demonstrate. In young children, septic arthritis often presents with mild symptoms and inconclusive laboratory findings. Even if the Gram preparation of the synovial fluid shows no micro-organisms, unusual pathogens may be isolated by means of an aerobic blood culture system.

Arthritis, Infectious↗
PubMed2000

Monocyte IL-10 production during respiratory syncytial virus bronchiolitis is associated with recurrent wheezing in a one-year follow-up study.

Respiratory syncytial virus (RSV) bronchiolitis is associated with subsequent recurrent wheezing episodes. To determine whether cytokine responses during infection can be of predictive value for the development of recurrent wheezing, we performed a follow-up study in 50 hospitalized children with RSV bronchiolitis. Monocyte and lymphocyte cytokine responses in vitro were studied during the acute phase of disease, and again during the convalescent phase, 3 to 4 wk later. Monocyte cytokine responses, including interleukin-10 (IL-10), were measured in whole blood cultures, stimulated with lipopolysaccharide and interferon-gamma (LPS + IFN-gamma). In addition, T-cell cytokine responses, including IFN-gamma and IL-4 production, were measured in whole-blood cultures stimulated with phytohemagglutinin (PHA) or alphaCD2 + alphaCD28. Cytokine responses were analyzed in relation to the development of recurrent episodes of wheezing, documented by parents in a diary during a 1-yr follow-up period. IL-10 responses during the acute phase of RSV bronchiolitis were comparable to those in healthy control subjects. During the convalescent phase, IL-10 responses were significantly increased in patients as compared with those in healthy control subjects (p < 0.001). At follow-up, 27 children (58%) had recurrent episodes of wheezing. IL-10 levels, measured during the convalescent phase, were significantly higher in patients who developed recurrent wheezing during the year after RSV bronchiolitis than in patients without recurrent episodes of wheezing (p = 0.006). Moreover, IL-10 responses during the convalescent phase correlated significantly with the number of wheezing episodes (r = 0.42, n = 46, p = 0.004). Interestingly, no association was found between IFN-gamma responses, IL-4 responses, or IFNgamma/IL-4 ratios and recurrent wheezing. We conclude that monocyte IL-10 responses in vitro upon stimulation with nonspecific stimuli may have predictive value for the development of recurrent wheezing after RSV bronchiolitis. Moreover, our results indicate that not only allergen-driven Th2 cytokine responses can lead to asthmatic symptoms but also virus-induced changes in cytokine responses may result in asthmatic symptoms.

Bronchiolitis, Viral↗
PubMed1999

Peripheral blood cytokine responses and disease severity in respiratory syncytial virus bronchiolitis.

The role of cellular immunity in disease severity in respiratory syncytial virus (RSV) bronchiolitis is largely unknown. This study investigated the association between disease severity and systemic cytokine responses in hospitalized ventilated and nonventilated RSV bronchiolitis patients. In whole blood cultures stimulated with phytohaemagglutinin (PHA), lymphoproliferative responses and interferon (IFN)-gamma and interleukin (IL)-4 production during acute illness were measured. In addition, plasma cytokines were measured. Measurements were repeated in the convalescent phase, 3-4 weeks after admission. Fifty patients were included. The median age in ventilaled patients was significantly lower than in nonventilated patients (1 versus 4 months, p<0.05). In comparison with nonventilated patients, the ventilated patients had significantly lower lymphoproliferative responses and a lower production of IFN-gamma and IL-4. In fact, IFN-gamma and IL-4 production in ventilated patients was almost completely undetectable. Plasma IL-8 levels in ventilated patients were significantly higher than in nonventilated patients. In the convalescent phase, lymphoproliferative and cytokine responses as well as plasma IL-8 levels were normal in both patient groups. Since RSV bronchiolitis is associated with the subsequent development of asthma, the possible skewing of the T-helper (Th1/Th2) cytokine balance was investigated. This was found neither in the acute nor in the convalescent phase. In conclusion, the data indicate that depressed lymphocyte function and elevated plasma interleukin-8 levels are markers of severe disease. It is suggested that age and maturation related immune mechanisms could explain the occurrence of severe respiratory syncytial virus bronchiolitis requiring mechanical ventilation in young infants.

Antibodies, Viral↗
PubMed1999

Increased tissue-type plasminogen activator antigen release is not accompanied by increased systemic fibrinolytic activity in severe neonatal respiratory distress syndrome.

Intravascular and intraalveolar fibrin depositions in preterm infants with severe respiratory distress syndrome (RDS) have been attributed to activation of clotting. We questioned whether in the face of activated clotting, fibrinolysis is sufficient in these infants. We found, in infants with severe RDS within 6 to 12 h of birth, increased median thrombin-antithrombin III complex formation (11.1 versus 1.3 ng/mL in the group with mild-to-moderate RDS, p < 0.001), indicating activation of clotting. Simultaneously, we found increased tissue-type plasminogen activator antigen (t-PA) release in plasma of these infants represented by increased median t-PA plasma concentrations (8.3 versus 2.5 ng/mL in the group with mild-to-moderate RDS, p < 0.01). This increased t-PA release was not accompanied with more plasminogen and antiplasmin consumption and with more fibrin and fibrinogen degradation than in the infants with mild-to-moderate RDS because plasma plasminogen and antiplasmin activity and total fibrin and fibrinogen degradation product concentrations were similar in both groups. We have found that activated clotting and t-PA plasma concentrations are positively correlated with arterial-to-alveolar oxygen tension ratio and ventilator efficiency index values. Plasminogen and antiplasmin activity, and total fibrin and fibrinogen degradation product concentrations were not correlated with these continuous measures of RDS severity. In neonatal RDS, clotting activity contributes to disease severity. Insufficient fibrinolysis likely facilitates the deleterious effects of activated clotting.

Antithrombin III↗
PubMed1997

Disease severity is correlated with plasma clotting and fibrinolytic and kinin-kallikrein activity in neonatal respiratory distress syndrome.

This study was undertaken to determine whether simultaneous activation of clotting, fibrinolysis, and kinin-kallikrein is associated with disease severity in preterm infants with neonatal respiratory distress syndrome (RDS), during the first 5 d of life. In the infants with severe RDS, we found activation of clotting, fibrinolysis, and kinin-kallikrein within 6-12 h of birth, indicated by increased thrombin-antithrombin III complex formation [22.5 ng/ml versus 1.4 ng/ml (median values) in the mild/moderate RDS infants, p < 0.001], increased tissue-type plasminogen activator plasma concentrations [5.1 ng/ml versus 2.6 ng/ml (median values) in the mild/moderate RDS infants, p < 0.01], and increased plasma kallikrein activity [198% versus 189% of maximal activated human plasma (median values) in the mild/ moderate infants, p < 0.01], respectively. Thrombin generation, tissue-type plasminogen activator release, and kallikrein activity did not change significantly in the severe RDS group throughout the study. In these infants, kallikrein activity was accompanied by lower values of plasma kallikrein inhibitory activity. Activation of clotting, fibrinolysis, and kinin-kallikrein was accompanied with a transient decrease of the neutrophil count and a steady decrease of the platelet count in the severe RDS group. The studied parameters of clotting and fibrinolytic and kinin-kallikrein activation were significantly correlated with continuous measures of RDS severity. We, therefore, suggest that this activation process likely contributes to respiratory insufficiency in neonatal RDS.

Antithrombin III↗
PubMed1997

Number and activation of circulating polymorphonuclear leukocytes and platelets are associated with neonatal respiratory distress syndrome severity.

OBJECTIVE: To determine whether number and activation of circulating polymorphonuclear leukocytes (PMNs) and platelets are associated with disease severity in neonatal respiratory distress syndrome (RDS). DESIGN: Prospective study. SETTING: Tertiary neonatal intensive care unit. PATIENTS: Preterm infants with severe (n = 18) or mild to moderate (n = 18) RDS who were consecutively admitted. INTERVENTIONS: PMN and platelet counts and plasma concentrations of elastase-alpha1-proteinase inhibitor (E-alpha1-PI) and thromboxane B2 (TxB2) were recorded each day during the first 5 days of life. E-alpha1-PI-to-PMN and TxB2-to-platelet ratios were calculated to correct for the influence of the PMN and platelet count on elastase and thromboxane release. RESULTS: From day 2, the severe RDS group had lower median PMN counts (1.5 vs 4.5 x 10/L), lower mean platelet counts (136 vs 230 x 10/L), and more elastase and thromboxane release, indicated by higher median E-alpha1-PI-to-PMN (39.2 vs 13.0 ng/10 PMNs on day 2) and TxB2-to-platelet (2.61 vs 0.52 pg/10 platelets on day 3) ratios than the mild-to-moderate group. Lower PMN and platelet counts and higher elastase and thromboxane release were correlated with birth asphyxia (lower 5-minute Apgar scores and umbilical arterial PH values), higher respiratory requirements (fraction of inspired oxygen and peak inspiratory pressure), and decreased values for continuous measures of RDS severity (ventilatory efficiency index and PaO2-to-alveolar oxygen tension ratio). CONCLUSION: Decreased PMN and platelet counts and increased elastase and thromboxane release are correlated with increased RDS severity. Birth asphyxia (hypoxia and acidosis) and tissue injury caused by high-pressure ventilation and hyperoxia may promote this activation process.

Humans↗
PubMed1997

Ureaplasma urealyticum colonization, prematurity and bronchopulmonary dysplasia.

The aim of the present study was to determine the association between the presence of Ureaplasma urealyticum in endotracheal aspirates and bronchopulmonary dysplasia (BPD). In addition, a review of similar studies from the English literature is presented. During the period February 1990 until March 1991, 108 mechanically-ventilated infants were included in a prospective study. Endotracheal aspirates were cultured for U. urealyticum. Birth weight, gestational age and development of BPD was recorded. Cultures were positive in 23 infants, resulting in a 21% colonization. The infants with positive cultures had a significantly lower gestational age (mean 28.9 vs 31.5 weeks; range 25-40 vs 25-42 weeks; p=0.0014). A positive U. urealyticum culture was not associated with a low birth weight (mean 1,390 vs 1,690 g; range 675-4,090 vs 700-3,600 g; p=0.0712). A positive U. urealyticum culture was significantly associated with BPD (p=0.0373). However, after correction for gestational age by logistic regression analysis, BPD failed to correlate with the presence of positive U. urealyticum cultures. A MEDLINE search of the English language literature was performed to identify all studies having the association of U. urealyticum colonization and BPD. Fourteen controlled studies were found. Five studies found no significant association between U. urealyticum colonization and BPD. In two studies, after correction for gestational age, the association between U. urealyticum colonization and BPD did not remain significant. In five studies with a significant association between U. urealyticum colonization and BPD, no correction for gestational age had taken place. In conclusion, U. urealyticum colonization is not associated with the development of bronchopulmonary dysplasia. U. urealyticum is often associated with gestational age and/or low birth weight; to investigate the association between U. urealyticum and bronchopulmonary dysplasia correction for both parameters should be made.

Bronchoalveolar Lavage Fluid↗
PubMed1996

Activation of circulating polymorphonuclear leukocytes in preterm infants with severe idiopathic respiratory distress syndrome.

We have studied activation of circulating polymorphonuclear leukocytes (PMN) in plasma of preterm infants with severe idiopathic respiratory distress syndrome (IRDS group, n = 15) and without IRDS (reference group, n = 15) during the first 5 postnatal days. We have observed lower median PMN counts in the IRDS group than in the reference group from d 2 (1.4 x 10(9)/L versus 4.8 x 10(9)/L in the reference group, p < 0.001) to d 4 to 6 (1.6 x 10(9)/L versus 4.0 x 10(9)/L, p < 0.01). Lower PMN counts in the IRDS infants were accompanied by lower median plasma elastase-alpha1-proteinase inhibitor (PI) concentrations (53.6 ng/mL versus 128.0 ng/mL in the reference group on d 2, p < 0.05). Simultaneously, median elastase-alpha1-PI/PMN ratios of these infants were significantly higher (40.8 ng/10(6) PMN versus 21.8 ng/10(6) PMN on d 2, p < 0.05), indicating activation of circulating PMN. Activation of circulating PMN in the IRDS group is associated with platelet-activating factor (PAF) release and complement activation from within 6 to 12 h of birth but not with release of tumor necrosis factor-alpha. PAF release was represented by significantly reduced inhibiting capacity (58% of normal human plasma, p < 0.01) and complement activation by higher median plasma C3a des-Arg concentrations (1680 ng/mL versus 325 ng/mL in the reference group, p < 0.001). We conclude that circulating PMN are activated in preterm infants with severe IRDS, which might be caused by systemic PAF release and complement activation. This activation process may play a role in the pathogenesis of the IRDS by influx of activated PMN into the lungs.

Complement C3a↗
PubMed1996

Leakage of protein into lungs of preterm ventilated rabbits is correlated with activation of clotting, complement, and polymorphonuclear leukocytes in plasma.

We investigated whether leakage of protein in lungs of preterm ventilated rabbits of 28- and 29-d gestational age is correlated with activation of clotting, complement, and polymorphonuclear leukocytes (PMN) in plasma. We found signs of systemic activation of clotting, complement and PMN in ventilated 28-d gestational age rabbits, as indicated, respectively, by increased median plasma fibrin monomer concentrations (83 versus 40% of normal adult rabbit plasma in nonventilated 28-d gestational age rabbits, p < 0.01), decreased median plasma CH50 activity (112 versus 122 U/L in nonventilated 28-d gestational age rabbits, p < 0.05), and increased median plasma beta-glucuronidase concentrations (159 versus 97% of maximal activated adult rabbit plasma in nonventilated 28-d gestational age rabbits p < 0.05). We did not find signs of systemic activation in the ventilated 29-d gestational age group. Higher median total protein concentrations in alveolar wash of the ventilated 28-d gestational age rabbits (2.7 versus 1.3 mg/mL in the nonventilated rabbits. p < 0.01) indicated protein leakage into the lungs, and this protein leakage was more pronounced in the lungs of ventilated 28-d gestational age rabbits than in those of ventilated 29-d gestational age rabbits (2.1 mg/mL, p < 0.01). The total protein concentration in the alveolar wash of all 28-d gestational age rabbits was correlated with the concentration of fibrin monomers (p = 0.51, p = 0.035) and beta-glucuronidase (p = 0.61, p = 0.011), and the CH50 activity (p = -0.73, p = 0.002) in plasma. We conclude that leakage of protein in lungs of preterm ventilated rabbits of 28-d gestational age is correlated with activation of clotting, complement, and PMN in plasma. This activation process may contribute to lung injury by intravascular and intraalveolar deposition of fibrin and formation of proteinaceous edema.

Animals↗