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Biomedical subjects

Avraham Avital

Publications and source records attributed to Avraham Avital.

14 recordsLinked to original sources

Effect of low altitude at the Dead Sea on exercise capacity and cardiopulmonary response to exercise in cystic fibrosis patients with moderate to severe lung disease.

Oxygen supplementation may improve exercise tolerance and the physiological response to exercise in cystic fibrosis (CF) patients. Elevated barometric pressure at low altitude is a simple means of increasing the quantity of inspired oxygen. Our objectives were to examine the effect of natural oxygen enrichment (at the Dead Sea, 396 m below sea level) on exercise capacity, and the physiological responses to maximal and submaximal exercise in CF patients. Patients were tested twice: at sea level (barometric pressure, 754 +/- 6 mmHg, mean +/- SD), and at the Dead Sea (barometric pressure, 791 +/- 3 mmHg), in a randomized crossover design. We studied 14 CF patients (6 females, 8 males), aged 15-45 years, with moderate to severe lung disease (mean forced expired volume in 1 sec = 50.0 +/- 11.2% predicted). Tests at each site included resting spirometry, anthropometry, a graded submaximal exercise test, a maximal exercise test on a treadmill, and a 6-min walk test. Tests were performed in identical order at both sites. Tests at the Dead Sea were performed 72 hr after arrival. No differences between sites were observed in lung function at rest. Peak oxygen consumption was significantly improved at the Dead Sea compared with sea level (1.68 +/- 0.73 vs. 1.57 +/- 0.74 l/min, respectively, P = 0.05), along with an improvement in the ventilatory equivalent for oxygen (41.2 +/- 6.3 vs. 46.1 +/- 7.1, respectively, P < 0.05). During submaximal exercise, blood oxygen saturation improved at the Dead Sea compared with sea level at all exercise intensities (P < 0.05). In conclusion, these results suggest that even a brief stay at the Dead Sea area may have physiological benefits for CF patients with moderate to severe lung disease.

Adolescent↗

Timing and nature of wheezing at the endpoint of a bronchial challenge in preschool children.

Bronchial reactivity to inhaled agents in preschool children can be undertaken by auscultating the lungs to detect wheezing, but there is a lack of information on when wheeze first appears at the endpoint of the challenge and on the acoustic characteristics of the wheeze. We recorded breath sounds continuously during tidal breathing inhalation challenges with adenosine 5'-monophosphate, using sensors attached over each upper lobe in 80 preschool children. In 35 children, the challenge was considered positive by a pediatrician who determined the endpoint by detecting wheeze on auscultation after an inhalation. Using acoustic analysis, we determined that the first wheeze appeared during the 2-min period of nebulization in 31% of positive challenges; it was unilateral in 37%, and only inspiratory in 46%. A running window of 6 sec was used to detect at least two wheezes without reference to phase of breathing, and this index had a sensitivity of 97.6% and specificity of 99.7% for determining the endpoint of a challenge. Detecting wheeze acoustically adds safety to the technique by enabling the challenge to be stopped earlier, while the lack of a need to document the phase of breathing simplifies the technique.

Acoustics↗

Poly-lactic-glycolic acid microspheres: a biodegradable marker for the diagnosis of aspiration in hamsters.

Aspiration is a major cause of lung disease in infants and young children. As the symptoms and signs of aspiration are not specific, the diagnosis is delayed due to a low index of suspicion and low sensitivity and specificity of the available diagnostic tests. In the present study, we evaluated the utility of microspheres composed of a degradable polymer, polylactic glycolic acid (PLGA), as a marker to diagnose aspiration in hamsters. Thirty hamsters underwent direct tracheal instillation of 0.1 mL of a suspension of PLGA. Eighteen other animals served as controls and underwent tracheal instillation of 0.1 mL of saline. Three animals served as naive controls and had no tracheal instillation. Five animals from the PLGA group and three from the saline group underwent whole-lung lavage (WLL) on days 1, 8, 15, 29, 43, and 58. PLGA microspheres were easily identified under light microscopy inside the alveolar macrophages obtained from WLL in all PLGA-instilled animals during all studied days. The number and size of PLGA microspheres within the alveolar macrophages decreased gradually with time with a 90% rate of disappearance of about 36 d. There was a marked neutrophilic response in lung lavage and a mild peribronchial neutrophil infiltration on the first day after tracheal instillation of PLGA which subsequently disappeared. We conclude that PLGA microspheres are a sensitive and specific marker for aspiration in hamsters. The usefulness of this test in diagnosing aspiration in humans should be further evaluated in clinical studies.

Animals↗

Amino-terminal pro-brain-type natriuretic peptide: heart or lung disease in pediatric respiratory distress?

OBJECTIVES: The aim of this study was to determine whether plasma levels of amino-terminal pro-brain natriuretic peptide (N-BNP) could differentiate between heart failure and lung disease among infants with acute respiratory distress. In addition, our aim was to determine whether plasma levels of N-BNP could be used to monitor the effects of treatment among infants with heart failure. METHODS: Infants (age range: 1-36 months; median age: 10 months) who presented with respiratory distress underwent physical examination, plasma N-BNP measurement, and echocardiography within 24 hours after admission. Seventeen infants were finally diagnosed with acute heart failure and 18 with acute lung disease. Thirteen healthy infants served as a control group. RESULTS: Plasma N-BNP levels were significantly higher for the infants with heart failure (median: 18452 pg/mL; range: 5375-99700 pg/mL) than for the infants with lung disease (median: 311 pg/mL; range: 76-1341 pg/mL). Among the infants with heart failure, there was a significant difference in plasma N-BNP levels before and after congestive heart failure treatment. CONCLUSION: Among infants with respiratory distress, plasma N-BNP measurements can differentiate between acute heart failure and lung disease and can be used to monitor the effects of treatment for infants with heart failure.

Acute Disease↗

CT of hemangiomas of the upper airways in children.

OBJECTIVE: Hemangiomas of the airways in infants are commonly diagnosed at bronchoscopy performed for the investigation of stridor or other respiratory symptoms. Occasionally on bronchoscopy the appearances are atypical or the entire extent of the suspected hemangioma cannot be appreciated. We report on the clinical usefulness of dynamic contrast-enhanced CT in the evaluation of suspected hemangiomas of the airways in infants. CT findings of 11 infants who underwent investigation for a suspected airway hemangioma were correlated with bronchoscopic findings. CONCLUSION: Dynamic contrast-enhanced CT is a valuable noninvasive method for the evaluation of airway hemangiomas. Although it can be used to confirm the diagnosis in patients with equivocal findings on bronchoscopy, we believe that CT findings are specific enough that CT can be recommended as the primary method of establishing the diagnosis. Multiplanar reconstructions illustrate the location, extent, and degree of luminal narrowing and any involvement of adjacent tissues.

Bronchial Diseases↗

Is clinical wheezing reliable as the endpoint for bronchial challenges in preschool children?

The present study was designed to compare the clinical finding of wheeze by auscultation with an objective evaluation by acoustic means at the endpoint of a bronchial challenge in preschool children. Challenges were undertaken using a tidal breathing method in 51 preschool children as part of the investigation of possible asthma. An electronic stethoscope was used for auscultation of each lung and for the simultaneous recording of the acoustic sonogram for analysis. In 24 children, the pediatrician determined that the challenge was positive, and in 22 of these, he heard wheezing at the endpoint of the challenge. In 2 children the challenge was considered positive, based on a modest fall in saturation. The acoustic record was scanned manually for presence of wheeze defined in terms of duration, and power spectrum without reference to auscultatory findings. In positive challenges, the mean wheeze rate was 28.1% (95% CI, 19.5-36.8%), while no wheeze was detected acoustically in negative challenges. Using a cutoff wheeze rate (duration of wheeze/duration of breath phase x100) of 10% for the whole group, clinical wheezing detected by the pediatrician had a sensitivity of 100% (no false negatives) and a specificity of 91%. In conclusion, the clinical observation of wheeze agrees very well with its detection by acoustic measurement at the endpoint of a bronchial challenge in preschool children.

Asthma↗

Familial concordance of phenotype and microbial variation among siblings with CF.

The clinical spectrum of cystic fibrosis (CF) is influenced by the cystic fibrosis transmembrane conductance regulator (CFTR) genotype. However, variable courses of the disease were demonstrated among patients with identical genotypes. Since siblings share identical CFTR mutations and environmental factors, they can serve as a model to assess the effect of modifier genes on disease expression, and also to evaluate cross-infection. The aim of this study was to compare disease expression among siblings with CF. All sibling pairs treated at 7 CF centers in Israel were included in the study. Data were collected from patients' medical charts. Fifty families with at least 2 siblings were identified. As expected, the second-born sibling was diagnosed at an earlier age compared to the first-born. The mode of CF presentation at diagnosis showed significant familial concordance. In the families where the first sibling presented with gastrointestinal manifestations, 79% of the second siblings also presented with gastrointestinal manifestations. When gastrointestinal manifestations were absent in the first sibling, only 12% of the second siblings presented with gastrointestinal manifestations (P < 0.0001). Likewise, when the first sibling presented with respiratory symptoms, 60% of the second siblings presented with the similar symptoms. However, when the first sibling presented without respiratory symptoms, only 12% of the second siblings presented with respiratory symptoms (P < 0.001). Meconium ileus (MI) was present in 20 patients (21%). In 10 families where the first-born sibling had MI, 8 (80%) of the subsequent siblings had MI. On the other hand, in the 39 families where the first-born sibling did not have MI, only 2 (5%) subsequent siblings had MI (P < 0.001). Pancreatic insufficiency (PI) also had high familial concordance (P < 0.0001). Percentile growth for weights and heights and lung function (FVC, FEV(1), and FEF(25-75)) at ages 7 and 10 years were similar between siblings. P. aeruginosa grew from sputum in 89% of our study patients. When P. aeruginosa was isolated from the first-born patient, 91% of the second siblings were also positive for P. aeruginosa, whereas when the initial sibling was not a carrier of P. aeruginosa, only 50% of subsequent siblings were positive (P < 0.0001). This familial concordance was not observed for S. aureus. By contrast, the age of first isolation of P. aeruginosa and S. aureus was significantly earlier in the second sibling than in the first for the two bacteria: 10.3 +/- 5.1 vs. 7.3 +/- 5.2 years (P < 0.05) for P. aeruginosa, and 11.5 +/- 5.4 years vs. 6.8 +/- 5.1 years (P < 0.05) for S. aureus. CF siblings tend to share similar phenotypes that are not mutation-dependent. The lack of variability between siblings in mode of initial CF presentation, rates of MI, pulmonary function, and nutritional status supports the role of modifier genes in the determination of these factors.

Adolescent↗

Simple and specific test for the diagnosis of aspiration into the airways using a corn flour-milk mixture in a hamster model.

Aspiration into the airways is one of the major causes of lung disease in infants and young children. Unfortunately, the diagnosis of aspiration is often delayed due to unawareness and low sensitivity and specificity of existing diagnostic tests. We tested the efficacy of a new method, using a mixture of corn flour in milk instilled into the trachea, to diagnose aspiration in a hamster model. Forty-five female hamsters were used for the experiments. Twenty hamsters underwent tracheal instillation of 0.1 ml of a mixture of 7.5% corn flour (containing starch granules with a diameter of 2-30 microm) in milk. Twenty control animals underwent tracheal instillation of saline. Five hamsters served as naive controls. Five animals from the corn flour and saline groups underwent bronchoalveolar lavage on days 1, 3, 7, and 14 after tracheal instillation. Starch granules were identified under light microscopy, using both iodine and Diff-Quik staining in all the corn flour-instilled animals and during all days after tracheal instillation. No starch granules were detected in naive or saline-treated animals. Starch granules were detected over 14 days following tracheal instillation, with a half-life rate of disappearance of about 6 days. Corn flour aspiration in hamsters can be easily identified by light microscopy, using simple laboratory techniques.

Animals↗

Exhaled nitric oxide is age-dependent in asthma.

We determined whether the exhaled nitric oxide (eNO) level in asthmatics is age-dependent. Eighty-seven asthmatic patients aged 2-41 years were studied. Hyperreactivity to adenosine 5'-monophosphate (AMP) was used to confirm asthma (</= 200 mg/ml). In the younger group of children (2-5 years), AMP challenge was performed by the provocation concentration causing wheeze (PCW) method, while in the older groups of patients (6-41 years), regular spirometry was used. Exhaled NO was measured in the younger group by the tidal breathing method (TBm) and in the older subjects by the slow vital capacity method (SVCm). TBm and SVCm were compared in 21 other subjects, and there was a significant correlation between the two values (r = 0.96, P < 0.0001). The equation of correlation between the two methods was eNOTBm = 0.78eNOSVCm - 0.51. Within asthmatic patients, we found a significant increase in eNO with age (P < 0.0001), while there was no significant difference in AMP reactivity (P = 0.35). We conclude that eNO in asthmatic patients is age-dependent, with lower values in young children.

Adenosine Monophosphate↗

The effect of montelukast on bronchial provocation tests and exhaled nitric oxide levels in asthmatic patients.

BACKGROUND: Leukotriene antagonist therapy in asthmatic patients alleviates symptoms and improves exercise tolerance, however the effect of these drugs on bronchial provocation tests and exhaled nitric oxide levels are less clearly established. OBJECTIVE: To determine the effect of montelukast treatment on airway hyperresponsiveness to exercise, methacholine and adenosine-5'-monophosphate and on exhaled nitric oxide levels in steroid-naive asthmatics. METHODS: Following a 2 week run-in period, 20 mild to moderate asthmatics were enrolled in an open label 6 week trial of oral montelukast-sodium therapy. Bronchial hyperreactivity (exercise, methacholine and adenosine-5'-monophosphate challenges) and exhaled nitric oxide levels were measured before and after the 6 week period. RESULTS: Montelukast treatment resulted in a significant improvement in exercise tolerance: median delta FEV1 20.0% (range 0-50) prior to treatment vs. 15.0% (range 0-50) post-treatment (P = 0.029). A significant difference was also observed for exhaled NO following therapy: median NO 16.0 ppb (range 7-41) vs. 13.0 (range 4.8-26) (P = 0.016). No change was seen in baseline lung function tests (FEV1, MEF50) or in the bronchial responsiveness (PC20) for methacholine and adenosine-5'-monophosphate. CONCLUSIONS: This study demonstrates that the leukotriene antagonist montelukast-sodium reduces bronchial hyperreactivity in response to exercise and reduces exhaled nitric oxide levels but has little effect on bronchial responsiveness to methacholine and adenosine challenges.

Acetates↗

Gavaging the infant lung.

An 8-month-old female infant was hospitalized for persistent bilateral infiltrates, failure to thrive, and tachypnea. An extensive diagnostic workup was negative, except for strong oil-red O staining of the white-turbid bronchoalveolar lavage fluid and borderline esophageal pH monitoring. Conservative treatment failed, and she was scheduled for gastrostomy and Nissen-fundoplication until the family physician found that the anxious mother was feeding the child forcibly, which caused chronic aspiration pneumonitis. The mother was given psychological support and was supervised, and the child recovered completely.

Anxiety Disorders↗

Polystyrene microspheres as a specific marker for the diagnosis of aspiration in hamsters.

The diagnosis of recurrent aspiration in young children is problematic because there is no specific gold standard test to be used. In the present work, normal saline or a suspension of white polystyrene microspheres in normal saline was instilled into hamsters' trachea (n = 42), and bronchoalveolar lavage (BAL) cytology, microsphere index (total microspheres/100 macrophages), and lung histology were followed for 90 d. Naive animals (n = 6) had no tracheal instillation. On Days 1, 3, 10, 32, 60, and 90 after tracheal instillation, animals were killed (saline-instilled animals, n = 3; and microsphere-instilled animals, n = 4), and BAL was performed. There was a marked inflammatory response in BAL on Day 1 after tracheal instillation of saline or microsphere suspension. White microspheres were clearly identified within alveolar macrophages in all studied days. Microsphere numbers showed a 50% disappearance rate of 10 d. A mild peribronchial inflammation was noted in lung histology only on Day 1 after instillation. Microspheres were not detected in extrapulmonary organs. We conclude that polystyrene microspheres instilled in hamsters' trachea can be easily identified in BAL macrophages for as long as 3 mo and could potentially be used as a sensitive, specific, and stable marker for the diagnosis of aspiration.

Animals↗

Charcoal is a sensitive, specific, and stable marker for the diagnosis of aspiration in hamsters.

The diagnosis of recurrent aspiration in young children is a perpetual challenge because there is no specific gold standard test to be used. The finding of lipid-laden alveolar macrophages in bronchoalveolar lavage (BAL) is a sensitive but nonspecific marker for the diagnosis of aspiration. We conducted a short-term study comparing tracheal instillation of saline, milk, or a milk-charcoal mixture in hamsters. BAL cytology, lipid-laden alveolar macrophage index, charcoal alveolar macrophage index, and lung histology were monitored for 10 d. A long-term study was performed, and hamsters were monitored for 92 d after milk-charcoal tracheal instillation. Baseline animals (n = 4) had no tracheal instillation. Saline- and milk-instilled animals had BAL performed after 1 (n = 4), 3 (n = 4), and 10 (n = 4) d. Milk-charcoal-instilled animals had BAL performed after 1 (n = 4), 3 (n = 4), 10 (n = 4), 30 (n = 2), 58 (n = 2), and 92 (n = 2) d after tracheal instillation. Total cell counts and percent neutrophils in BAL fluid increased significantly and similarly after milk and milk-charcoal instillation on d 1 compared with baseline and saline-instilled animals. Lipid-laden alveolar macrophage index increased significantly only on d 3 after milk and milk-charcoal instillation compared with all days in the saline-instillation group. Charcoal alveolar macrophage index increased significantly after milk-charcoal instillation (d 1-58) from baseline or all days in the saline-instillation group. We conclude that charcoal particles instilled in tracheas of hamsters can be easily identified in BAL fluid and in lung parenchyma for as long as 3 mo after a single instillation and could potentially be used as a sensitive, specific, and stable marker for the diagnosis of aspiration, although the issue of its applicability to humans is still unsolved.

Animals↗

Short-term acupuncture therapy is of no benefit in patients with moderate persistent asthma.

STUDY OBJECTIVES: Acupuncture traditionally has been used to treat asthma. Nevertheless, only a few controlled studies have been performed to determine the efficacy of this treatment. Our study aimed to determine the efficacy of acupuncture in patients with moderate persistent asthma. METHODS: Twenty-three patients with moderate persistent asthma who had been treated only with inhaled beta(2)-agonists were randomly assigned to receive four sessions of real acupuncture (RA) or sham acupuncture (SA) in a blinded manner. After a washout period of 3 weeks, the patients were crossed over. Monitoring included FEV(1), methacholine challenge, daily peak flow (PF) variability, and the keeping of an asthma diary. RESULTS: Twenty of 23 patients completed the study. There was no significant change in FEV(1) following treatment. The mean (+/- SE) FEV(1) values before and after the RA were 73 +/- 4% and 73 +/- 3%, respectively (not significant [NS]). FEV(1) values before and after SA were 70 +/- 3% and 70 +/- 3%, respectively (NS). There was also no change in provocative methacholine concentration causing a 20% fall in FEV(1) (PC(20)) before and after treatment. The mean PC(20) values before and after RA were 0.92 +/- 0.42 mg/mL and 1.16 +/- 0.51 mg/mL, respectively (p = 0.71), while the PC(20) values before and after SA were 1.47 +/- 0.83 mg/mL and 1.11 +/- 0.79 mg/mL, respectively (p = 0.59). There was no change in the mean PF variability before and after the RA (1.6 +/- 3.1% and 1.8 +/- 2.3%, respectively [NS]). The PF variability before and after SA were 3.6 +/- 2.8% and 2.8 +/- 3.4%, respectively (NS). No significant difference was demonstrated for symptom scores or for the use of beta(2)-agonist inhalers (RA, 6.7 +/- 3.4; SA, 8.1 +/- 3.6; p = 0.58). CONCLUSION: In patients with moderate persistent asthma, a short course of acupuncture treatment resulted in no change in lung functions, bronchial hyperreactivity, or patient symptoms.

Acupuncture↗