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Opinions differ as to the need of a lateral radiograph for diagnosing community acquired pneumonia in children referred to the emergency department. A lateral radiograph increases the ionizing radiation burden but at the same time may improve specificity and sensitivity in this population.To determine the value of the frontal and lateral chest radiographs compared to frontal view stand-alone images for the management of children with suspected community acquired pneumonia seen in a pediatric emergency department.Chest radiographs from 451 children with clinically suspected pneumonia were retrospectively reviewed. Interpretation of frontal views was compared to interpretation of combined frontal and lateral view, the latter being the gold standard.Findings consistent with bacterial pneumonia were diagnosed in 94 (20.8%) of the frontal stand-alone radiographs and in 109 (24.2%) of the combined frontal and lateral radiographs. The sensitivity, specificity, positive predictive value, and negative predictive value of the frontal radiograph alone were 86.2%, 93.9%, 81.7%, and 95.5%, respectively. False positive and false negative rates were 15% and 21%, respectively, for the frontal view alone. The number of lateral radiographs needed to diagnose one community acquired pneumonia was 29.The lateral chest radiograph improves the diagnosis of pediatric community acquired pneumonia to a certain degree and may prevent overtreatment with antibiotics.

SummaryBackgroundThe exercise challenge test (ECT) is a common tool for assessment of asthma in children. Many studies suggest that the “time to maximal bronchoconstriction” (Nadir-t) after exercise challenge in asthmatic children may be age-dependent, although this has never been systematically studied. Such findings may influence epidemiological surveys where the schedule of post-exercise measurements is trimmed. This study systematically assesses the relation between age and time to maximal bronchoconstriction post-ECT.MethodsData were collected retrospectively from 131 subjects (87 male; 3–18 years) who were referred for ECT. The routine ECT was performed according to ATS recommendation of a 6-min run. Spirometry was measured at 1, 3, 5, 10, 15, and 20min post-exercise. The post-exercise nadir of FEV1 (%baseline) (FEV1-nadir) and the time to maximal fall in Nadir-t (minutes) were sought and values were related to age.ResultsBaseline FEV1 values (mean±SD) were 90.5±13.8% predicted. FEV1-nadir was −23.6±11.7% from baseline values. The Nadir-t was reached at 5.1±2.6min (range 2–12min). A positive correlation between children's age and Nadir-t was observed (r2=0.542; SD of residuals=1.79; p

Bilevel positive airway pressure ventilation (BIPAP) has been used in cystic fibrosis (CF) patients as a bridge to transplantation. Our aim was to evaluate the effect of BIPAP use before transplantation on post-transplantation morbidity and mortality. We performed a retrospective study at a tertiary care center. Twelve CF patients (9 males; mean age = 26 years) were assessed. Group 1 consisted of eight patients that did not use BIPAP before lung transplantation. Group 2 comprised four patients who used BIPAP for 3–15 months while awaiting transplantation. Patients were evaluated before and two to ten years after transplantation. All eight patients who did not use BIPAP died two months to ten years after transplantation. All four BIPAP users are alive with no evidence of bronchiolitis obliterans two to eight years after lung transplantation. We demonstrated a significant improvement in acid-base balance (p

Spirometry data in cystic fibrosis (CF) patients in early childhood is scarce, and the ability of spirometry to detect airways obstruction is debatable.To evaluate the ability of spirometry to detect airflow obstruction in CF patients in early childhood.CF children (age range, 2.5 to 6.9 years) in stable clinical condition were recruited from five CF centers. The children performed guided spirometry (SpiroGame; patented by Dr. Vilzone, 2003). Spirometry indices were compared to values of a healthy early childhood population, and were analyzed with relation to age, gender, and clinical parameters (genotype, pancreatic status, and presence of Pseudomonas in sputum or oropharyngeal cultures).Seventy-six of 93 children tested performed acceptable spirometry. FVC, FEV1, forced expiratory flow in 0.5 s (FEV0.5), and forced expiratory flow at 50% of vital capacity (FEF50) were significantly lower than healthy (z scores, mean +/- SD: - 0.36 +/- 0.58, - 0.36 +/- 0.72, - 1.20 +/- 0.87; and - 1.80 +/- 1.47, respectively; p0.01); z scores for FEV1 and FVC were similar over the age ranges studied. However, z scores for FEV0.5 and forced expiratory flow at 25 to 75% of vital capacity were significantly lower in older children compared to younger children (p0.001), and a higher proportion of 6-year-old than 3-year-old children had z scores that were2 SDs below the mean (65% vs 5%, p0.03). Girls demonstrated lower FEF50 than boys (z scores: - 2.42 +/- 1.91 vs - 1.56 +/- 1.23; p0.001). Clinical parameters evaluated were not found to influence spirometric indices.Spirometry elicited by CF patients in early childhood can serve as an important noninvasive tool for monitoring pulmonary status. FEV0.5 and flow-related volumes might be more sensitive than the traditional FEV1 in detecting and portraying changes in lung function during early childhood.

BACKGROUND Increased upper respiratory infection (URI) among children at the beginning of school year is well known to parents and pediatricians. However, this phenomenon is not well documented or characterized. METHODS Computerized datasets from a large health maintenance organization in Israel were used to calculate the weekly rates of URI among children 3-14 years old for the years 2007-2012. In addition, nasopharyngeal swabs were collected in 2010-2012 from children with URI symptoms and controls during school opening time. Swabs were tested by real-time polymerase chain reaction for the presence of respiratory viruses. RESULTS Time-series analysis demonstrated a peak of URI in September each year. The peaks reached their height 2 weeks after school opening and returned to baseline within 4-7 weeks. The main 3 viruses detected both in URI patients and in healthy controls during the first weeks of school opening were rhinovirus, adenovirus and enterovirus. The detection rate of any respiratory virus, and of rhinovirus in particular, was significantly higher among cases than among controls (54% vs. 16%, P < 0.001 for any virus, and 35% vs. 6.0%, P < 0.01 for rhinovirus). When adjusting for age and sex cases had 5.8 times more viral detection when compared with controls. Upper respiratory symptoms were significantly more prevalent among the virus-positive cases when compared with negative ones. CONCLUSIONS Back-to-school illness consisting of URI has a distinct epidemiological pattern demonstrating a rapid rise peaking within 2 weeks of school opening and is associated predominantly with rhinovirus.

Management of pain and anxiety is an important part of patient care in the pediatric emergency department (ED). Even though it has improved significantly over the past few years, it is still suboptimal. The objective of this study was to evaluate the effect of informal and formal education on pain and anxiety management in the pediatric ED. Management of pain and anxiety was assessed by comparing the use of analgesics and sedatives during three phases: A) year 2000 (baseline), B) years 2001-2002 (informal teaching) and C) year 2004 (following a structured simulation-based training in pediatric sedation and analgesia). During period B there was a significant increase in the yearly use of eutectic mixture of local anesthetics (EMLA) (RR=2.63, CI 1.23-5.6), ibuprofen (RR=14.16, CI 8.73-22.98), midazolam (RR=1.68, CI 1.39-2.03) and nitrous oxide (N2O) in comparison with period A, with an additional increment of the first three medicines during period C. There was no change in the use of ketamine, morphine and meperidine during period B. Whereas, during period C, a significant increase in the use of ketamine and morphine was demonstrated (RR=24.56, CI 10.71-56.3 and RR=3.07, CI 2.12-4.44, respectively), while the use of meperidine (RR=0.68, CI 0.49-0.94) and N2O (RR=0.46, 95% CI 0.32-0.67) declined significantly. Educational interventions have a clear impact on pain and anxiety management demonstrated by the subsequent change in the use of sedatives and analgesics and should be provided to pediatric ED physicians. Informal teaching affected mainly the use of milder sedatives and analgesics, while formal structured training influenced the use of opioids and dissociative agents.

To explore the role of respiratory interactive computer games in teaching spirometry to preschool children, and to examine whether the spirometry data achieved are compatible with acceptable criteria for adults and with published data for healthy preschool children, and whether spirometry at this age can assess airway obstruction.Feasibility study.Community kindergartens around Israel and a tertiary pediatric pulmonary clinic.Healthy and asthmatic preschool children (age range, 2.0 to 6.5 years).Multi-target interactive spirometry games including three targets: full inspiration before expiration, instant forced expiration, and long expiration to residual volume.One hundred nine healthy and 157 asthmatic children succeeded in performing adequate spirometry using a multi-target interactive spirometry game. American Thoracic Society (ATS)/European Respiratory Society spirometry criteria for adults for the start of the test, and repeatability were met. Expiration time increased with age (1.3 +/- 0.3 s at 3 years to 1.9 +/- 0.3 s at 6 years [+/- SD], p0.05). FVC and flow rates increased with age, while FEV1/FVC decreased. Healthy children had FVC and FEV1 values similar to those of previous preschool studies, but flows were significantly higher (1.5 SD for forced expiratory flow at 50% of vital capacity [FEF50] and forced expiratory flow at 75% of vital capacity [FEF75], p0.005). The descending part of the flow/volume curve was convex in 2.5- to 3.5-year-old patients, resembling that of infants, while in 5- to 6-year-old patients, there was linear decay. Asthma severity by Global Initiative for Asthma guidelines correlated with longer expiration time (1.7 +/- 0.4 s; p0.03) and lower FEF50 (32 to 63%; p0.001) compared to healthy children. Bronchodilators improved FEV1 by 10 to 13% and FEF50 by 38 to 56% of baseline.Interactive respiratory games can facilitate spirometry in very young children, yielding results that conform to most of the ATS criteria established for adults and published data for healthy preschool children. Spirometric indexes correlated with degree of asthma severity.

Morbidity and mortality in cystic fibrosis patients is mainly attributed to pulmonary infection and inflammation. Chemokines play a pivotal role in the inflammatory process. Although genotype-phenotype correlation in cystic fibrosis patients has been defined, a clear relationship between the defect in the cystic fibrosis transmembrane regulator (CFTR) gene and pulmonary inflammation has not been established. The aim of this study was to assess whether serum chemokines levels in cystic fibrosis patients correlate with genotype and pulmonary function tests, as well as with other clinical characteristics. Serum levels of interleukin-8, RANTES, and monocyte chemoattractant protein-1 were measured in 36 cystic fibrosis patients grouped according to their genotype. Group A included 25 patients who carried two mutations associated with a pathological sweat test and pancreatic insufficiency (deltaF508, W1282X, G542X, N1303K, S549R). Group B included 11 compound heterozygote patients who carried one mutation known to cause mild disease with borderline or normal sweat test and pancreatic sufficiency (3849+10kb C to T, 5T). Associations between chemokine levels, genotype, pulmonary function, Pseudomonas aeruginosa colonization, age, sweat chloride level, and pancreatic and nutritional status were examined. Mean interleukin-8 and monocyte chemoattractant protein-1 levels were significantly higher in group A than group B (11.4 +/- 2.1 pg/ml vs. 5 +/- 0.9 pg/ml and 157 +/- 16 pg/ml vs. 88.8 +/- 16.4 pg/ml, respectively) (P0.01). No difference in RANTES levels were found between groups. interleukin-8 levels were inversely related to forced expiratory volume in 1 s (r = -0.37, P0.02), while there was no association between the latter and RANTES and monocyte chemoattractant protein-1 levels. The Pseudomonas colonization rate was higher among group A patients than group B (88% vs. 40%, P0.01). No relationship was found between measured chemokines and age, sweat chloride levels, and pancreatic and nutritional status. Our study demonstrates an association between interleukin-8, forced expiratory volume, and cystic fibrosis genotype. Hence, elevated interleukin-8 serum levels could serve as an indicator of an early inflammatory process and encourage the initiation of anti-inflammatory treatment.

Physicians and physiotherapists who care for CF patients have recommended the use of trampolines as a physiotherapeutic tool for enhancing cardiopulmonary performance, encouraging sputum production, and improving general well-being. Despite some therapeutic and recreational benefits associated with trampoline use, papers in the general pediatric population mostly document an increased incidence of injuries, ranging from minor trauma to spinal cord injuries and even death. The aim of this review is to examine the accumulated published data regarding the use of trampolines, to assess their potential contributions and disadvantages for CF patients, and to define whether trampoline use should be recommended. An extensive search in the published medical literature retrieved approximately 60 articles that primarily dealt with trampolines, out of which only two dealt with CF. The preponderance of these articles are reports pertaining to injuries related to the use of trampolines, with only a few describing the medical, physiologic, and/or psychological benefits of trampolines. Based on the accumulated data, the presumed benefits of trampoline use for CF patients are not proven. Furthermore, the suggested benefits could be acquired using other types of exercise. Weighing the known risks of trampolines against the potential benefits that are not unique to this modality suggests that the use of trampolines for CF should not be recommended.

Liver disease is the second cause of death in cystic fibrosis. The most deleterious complication of liver disease is portal hypertension, which has an estimated prevalence of up to 8%. Portal hypertension may manifest itself by splenomegaly, hypersplenism, gastro-oesophageal bleeding and ascites. The aim of our study was to determine the prevalence, risk factors and invasive management of portal hypertension at our centre.One hundred and fifty patients with cystic fibrosis were followed up between 1975 and 2000 in the national cystic fibrosis centre in Israel. Forty patients (27%) had liver disease. All underwent clinical evaluation and laboratory and imaging studies.Portal hypertension was diagnosed in 10 patients (7%), of whom eight were male. The mean age at diagnosis was 11 years (range, 4-17 years). All had severe mutations of the cystic fibrosis transmembrane conductance regulator gene (the CFTR gene), pancreatic insufficiency, meconium ileus or distal intestinal obstruction syndrome and variceal bleeding. Seven patients underwent sclerotherapy to control acute bleeding. Four underwent portosystemic shunting (functioning up to 37 years). Two patients with severe lung and liver disease underwent transjugular intrahepatic portosystemic shunting, which provided bleeding control, but both died while waiting for lung/liver transplantation. One patient underwent liver transplantation due to liver failure and still had good liver and lung function 10 years later.Portal hypertension is more common among Israeli patients with cystic fibrosis. The unique genetic composition of our population may explain this phenomenon. Risk factors include male gender, pancreatic insufficiency, severe CFTR mutations, meconium ileus and meconium ileus equivalent. Sclerotherapy is the main option to control oesophageal variceal bleeding, while portosystemic shunts offer a prolonged alternative treatment for refractory bleeding. A transjugular intrahepatic portosystemic shunt and liver transplantation may also be effective, but further research is required in order to establish their role.

Patients with normal or borderline sweat tests present a diagnostic challenge. In spite of the availability of genetic analysis and measurement of nasal potential difference, there is still uncertainty in diagnosing cystic fibrosis in some patients. CA 19-9 is a tumor-associated antigen whose levels were previously found to be elevated in some cystic fibrosis patients. We investigated whether serum CA 19-9 levels can contribute to establishing the diagnosis of cystic fibrosis in patients with a borderline sweat test, and evaluated the influence of different clinical variables on CA 19-9 levels. Serum CA 19-9 levels were measured in 82 cystic fibrosis patients grouped according to their genotype and in 38 healthy individuals. Group A included 50 patients who carried two mutations previously found to be associated with a pathological sweat test and pancreatic insufficiency (DeltaF508, W1282X, G542X, N1303K, and S549R). Group B included 13 compound heterozygote cystic fibrosis patients who carried one mutation known to cause mild disease with a borderline or normal sweat test and pancreatic sufficiency (3849+10kb C-->T, 5T). Group C included 38 normal controls. Nineteen cystic fibrosis patients carried at least one unidentified mutation. An association between CA 19-9 levels and age, pulmonary function, pancreatic status, sweat chloride, previous pancreatitis, serum lipase, meconium ileus, distal intestinal obstruction, liver disease, and diabetes was investigated. The distribution of CA 19-9 levels was significantly different between the three groups ( p

Pediatric emergency department chest radiographs are frequently interpreted by the pediatrician, and patient management is based on this interpretation.The purpose of this study was to assess the chest radiograph interpretation discordance rate between pediatricians and pediatric radiologists and determine its clinical significance.This study included 1196 patients admitted off-hours to the pediatric emergency department who had chest radiographs as part of the clinical evaluation. The pediatricians' interpretations of the chest radiographs as appeared in the discharge reports were reviewed and compared with the specialist radiologist's ultimate report.Discordant chest radiograph interpretations were found in 332 (28%) of 1196 patients. Of these, 76 (6.3%) were clinically significant. These included 59 initial diagnoses of normal or viral patterns subsequently interpreted as bacterial pattern by the radiologist and 17 radiographs with findings such as chronic lung disease or abnormal heart shadow overlooked or misinterpreted by the pediatrician.Although the clinically significant discordant rate was relatively low, daily chest radiograph reassessment by pediatric radiologists in a joint meeting with pediatricians has an added value for patient safety, quality assurance, and mutual training.

Background: Cytokine-inducible leucocyte-endothelial adhesion molecules were shown to affect the postoperative inflammatory response following cardiopulmonary bypass (CPB). Soluble P-selectin (sP-selectin) is one of these molecules. We investigated the correlation between plasma sP-selectin levels and the intra- and postoperative course in children undergoing CPB. Methods: Serial blood samples of 13 patients were collected preoperatively upon initiation of CPB and seven times postoperatively. Plasma was recovered immediately and frozen at – 70°C until use. Circulating soluble selectin molecules were measured with a sandwich enzyme-linked immunoabsorbent assay technique. Results: The significant post-CPB changes in sP-selectins plasma levels were associated with patient characteristics, operative variables and postoperative course. sP-selectin levels correlated significantly with surgery time, aortic cross-clamping time and inotropic support, as well as with the postoperative Pediatric Risk of Mortality score, hypotension and tachycardia. Conclusions: A relation between CPB-induced mediators and both early and late clinical effects is suggested. The up-regulation and expression of sP-selectin indicate neutrophil activation as a possible mechanism for the increase, and inhibiting it may reduce the inflammatory response associated with CPB.

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene containing a premature termination signal are expected to produce little or no CFTR chloride channels. It has been shown in vitro, that aminoglycoside antibiotics can increase the frequency of erroneous insertion of nonsense codons hence permitting the translation of CFTR alleles carrying missense mutations to continue reading to the end of the gene. This led to the appearance of functional CFTR channels at the apical plasma membrane. The aim of this research was to determine if topical application of gentamicin to the nasal epithelium of patients with cystic fibrosis (CF) carrying stop mutations can express, in vivo, functional CFTR channels. Nine CF patients carrying stop mutations (mean age 23 +/- 11 yr, range 12 to 46 yr) received gentamicin drops (0.3%, 3 mg/ml) three times daily intranasally for a total of 14 d. Nasal potential difference (PD) was measured before and after the treatment. Before gentamicin application all the patients had abnormal nasal PD typical of CF. After gentamicin treatment, significant repolarization of the nasal epithelium representing chloride transport was increased from -1 +/- 1 mV to -10 +/- 11 mV (p < 0. 001). In conclusion, gentamicin may influence the underlying chloride transport abnormality in patients with CF carrying stop mutations.

Patients with normal or borderline sweat test present a diagnostic challenge. In spite of the availability of different methods such as genetic analysis and measurements of nasal potential difference, uncertainty in diagnosing cystic fibrosis (CF) in some patients still exists. Neonates with CF have high serum lipase levels, which decline over time in pancreatic-insufficient patients, whereas pancreatic-sufficient patients demonstrate high serum lipase levels beyond infancy. Because patients with borderline or normal sweat test are almost always pancreatic sufficient, this study was aimed to assess whether serum lipase levels may be of help in establishing the diagnosis of CF in these patients. Serum lipase levels were measured in 100 CF patients and in 17 healthy individuals. Patients were grouped according to their genotype. Group A patients (n = 70) carried two mutations previously found to be associated with a pathologic sweat test and pancreatic insufficiency (delta F508, W1282X, G542X, N1303K, S549R). Group B (n = 30) were compound heterozygote patients who carried one mutation known to cause mild disease with borderline or normal sweat tests and pancreatic sufficiency (3849+10kb C-->T, 5T). Group C included 17 healthy controls. Serum lipase levels ranged between 2 and 104.4 U/L (mean +/- SD 16.9 +/- 14.7), 6.1-200 U/L (mean +/- SD 53.9 +/- 47.9), and 8.5-27.8 U/L (mean +/- SD 16.9 +/- 5.1) in Groups A, B, and C, respectively, with some overlapping between groups. The distribution of lipase levels was significantly different in Group B vs Groups A and C (P < 0.01). High lipase levels were found in 63.3% (19/30) of Group B patients, but in only 4.3% (3/70) and 0% (0/17) of Group A and C, respectively. Lipase levels were found to be inversely related to sweat chloride concentrations (r = -0.19, P < 0.05). Patients with borderline or normal sweat tests had high lipase levels, whereas low lipase levels were associated with pathologic sweat tests. Our findings indicate that the serum lipase level is genetically determined and that it has a useful role in the diagnosis of CF. Thus, in patients with borderline sweat tests and high lipase levels, the diagnosis of CF should be considered.

Determination of pancreatic function is essential in cystic fibrosis. The most-reliable method is by measuring pancreatic enzymes in the duodenum following intravenous or oral stimulation. However, this is invasive, time consuming, and expensive. Indirect tests are non-invasive but lack accuracy. This study examines a simple test which combines pancreatic stimulation by Lundh meal and sequential serum lipase measurements. The test was performed on three groups: group A, 36 cystic fibrosis patients carrying two mutations associated with severe disease and pancreatic insufficiency (delta F508, W1282X, G542X, N1303K, S549R); group B, 8 compound heterozygote cystic fibrosis patients carrying one mutation causing mild disease with pancreatic sufficiency (3849 + 10 kb C--T); group C, 17 healthy individuals. Basal lipase levels were 2-16.5, 16.4-73, and 8.5-27.8 U/l in groups A, B, and C, respectively, with some overlapping between groups. There were three patterns of lipase activity (1) consistently low levels (group A) suggested a severely affected insufficient pancreas; (2) normal basal levels followed by a linear rise peaking 30 min after the meal (found in 16 of 17 healthy individuals and 3 patients of group B) reflecting an unaffected sufficient pancreas; (3) elevated lipase levels not influenced by the meal (5 patients of group B). This reflects an ongoing destructive process in the pancreas which will eventually result in conversion from pancreatic sufficiency to pancreatic insufficiency. Hence serum lipase activity prior to and 30 min after Lundh meal is a good indicator of pancreatic status allowing categorization of cystic fibrosis patients as pancreatic insufficient, pancreatic sufficient, or pancreatic sufficient with late conversion to insufficiency.

Disease severity varies among cystic fibrosis (CF) patients carrying the same CFTR genotype. Here we studied the mechanism underlying disease variability in individuals carrying a splicing CFTR mutation, 3849+10 kb C--T. This mutation was shown to produce both correctly and aberrantly spliced CFTR transcripts containing an additional cryptic exon. Semiquantitative nondifferential RT-PCR showed considerable variability in the level (0-28%) of aberrantly spliced RNA transcribed from the 3849+10 kb C--T mutation in nasal epithelium from 10 patients. A significant inverse correlation was found between the level of the aberrantly spliced CFTR transcripts and pulmonary function, expressed as FEV1 (r = 0.92, P0.0001). Patients with normal pulmonary function (FEV180% predicted) had lower levels of aberrantly spliced CFTR RNA (0 to 3%) than those with FEV180%, (9 to 28% aberrantly spliced RNA). Only aberrantly spliced CFTR RNA was detected in the lung of a patient with severe lung disease who underwent lung transplantation. Our results show that the severity of CF lung disease correlates with insufficiency of normal CFTR RNA. Thus, the regulation of alternative splice site selection may be an important mechanism underlying partial penetrance in CF. Further understanding of this regulation will contribute to potential therapy for patients carrying splicing mutations in human disease genes.

Some patients express various features of cystic fibrosis (CF) even though essential characteristics of the disease might be absent. Such patients may suffer from respiratory disease without pancreatic insufficiency and normal sweat chloride levels. Others may present as male infertility because of congenital bilateral aplasia of the vas deferens (CBAVD) with no other signs of CF. The 5T allele, a DNA variant in a noncoding region of the cystic fibrosis transmembrane conductance regulator (CFTR) gene that reduces the level of the normal CFTR transcripts, was found in increased frequency among male patients with CBAVD. The purpose of this study was to investigate the possibility that the 5T allele is associated with dysfunction of organs other than the male reproductive system, leading to CF or atypical CF. Analysis of the 5T allele was performed on 148 subjects (29 with CF, 61 with atypical CF, and 58 with CBAVD) carrying 232 chromosomes with unidentified CFTR mutations, and on 142 non-CF chromosomes from healthy subjects of Ashkenazi origin. The frequency of the 5T allele among chromosomes from patients of Jewish Ashkenazi origin with CF and atypical CF (six of 33; 18%) was significantly higher than the frequency in the normal Ashkenazi population (eight of 142; 6%; p = 0.03). Analysis of the clinical presentation of the five patients with CF and the 12 patients with atypical CF carrying the 5T allele indicated that most patients suffered from respiratory disease presenting as asthma like symptoms, nasal polyposis, chronic sinusitis, chronic bronchitis, or bronchiectasis. Six patients had pancreatic insufficiency, two with meconium ileus. Sweat Cl- levels ranged from normal to elevated. Of the six male patients with respiratory disease who were old enough to be evaluated for fertility status, five were fertile and one had pancreatic insufficiency. Among male patients with CBAVD, 41% suffered from respiratory symptoms. Thus, the 5T allele is a variant with partial penetrance causing disease with an extreme variability of clinical presentation: from normal healthy fertile subjects or male patients with CBAVD to those with atypical or typical clinical phenotype of CF.

We report a case of intestinal perforation in a 20 month old girl following the ingestion of 2 small magnets. Ingestion of multiple magnets constitutes a unique problem. Magnets in adjacent intestinal loops may forcefully attract each other and produce pressure necrosis of the bowel wall, leading to perforation, fistula formation or intestinal obstruction. Therefore, these children should be observed carefully. Early surgical intervention should be considered when clinical symptoms develop, especially when, on sequential abdominal radiographs, there is no change in the magnets' location. Since toys with small magnets are ubiquitous, efforts should be made to increase parents' awareness on the one hand, and to alert toy manufacturers on the other hand.

In all, 58 couples suffering from infertility because of congenital bilateral absence of the vas deferens underwent a total of 67 combined microsurgical epididymal aspiration or testicular sperm extraction (TESE) and in-vitro fertilization (IVF) treatments. The oocytes recovered were inseminated by either the microdroplet IVF technique (n = 20), subzonal insemination (SUZI ; n = 10) or intracytoplasmic sperm injection (ICSI ; n = 37). Of the ICSI cycles, 12 were performed using spermatozoa obtained by TESE. Fertilization rates for epididymal spermatozoa were significantly higher for SUZI (17.9%, 17/95) and ICSI (34.4%, 137/398) than for microdroplet IVF (5.2%, 18/343) cycles. The proportion of cycles in which fertilization was achieved was higher in the SUZI (80%) and ICSI (95%) cycles than in the IVF cycles (45%). Delivery or an ongoing pregnancy was achieved in one (5%) IVF cycle, two (20%) SUZI cycles and seven (18.9%) ICSI cycles. SUZI or ICSI using epididymal or testicular spermatozoa significantly improved the oocyte fertility rate. The ICSI procedure was especially advantageous in patients for whom spermatozoa were obtained from a testicular biopsy.

Infants undergo various painless imaging procedures frequently. Mild sedation is required in such cases to reduce anxiety as well as to ensure optimal performance of the procedure. The most frequently used sedative as a single drug is chloral hydrate. The issue of preprocedural fasting is a subject of contention. The purpose of this study was to assess the effect of the American Academy of Pediatrics (AAP)/American Society of Anesthesiology (ASA) fasting practice guidelines on the efficacy and success of the sedation with chloral hydrate.The sedation records of 200 infants from 2 hospitals who underwent auditory brainstem response for evaluation of hearing loss were evaluated retrospectively. In the first hospital (group A), strict nulla per os (NPO) guidelines were followed in accordance with the guidelines published by the AAP/ASA, whereas in the second hospital (group B), no fasting period was required. All children were premedicated with chloral hydrate. We evaluated the sedation failure rate, total dose of chloral hydrate needed, adverse effects, overall sleep time, and time to discharge.The average fasting period as expected was significantly longer in group A patients than in group B patients (5.7 +/- 1.7 vs. 2 +/- 0.2 hours; P0.001). Group A patients demonstrated a significantly higher failure rate to achieve sedation with the first dose of chloral hydrate compared with group B patients (21% vs.11%; P = 0.03), hence needing higher doses (83 +/- 31 vs. 61 +/- 21 mg/kg; P0.01), and were sedated for longer periods (103 +/- 42 vs. 73 +/- 48 minutes; P0.001) and discharged later. No difference was found in the adverse effect rate.Fasting was associated with an increased failure rate of the initial sedation. As a consequence, an increased total dose of chloral hydrate was required inducing a prolonged sedation time. Presumably, this is a result of the fact that a hungry child is irritable and therefore more difficult to sedate.

The effect of nonsense mutations on mRNA levels is variable. The levels of some mRNAs are not affected and truncated proteins are produced, while the levels of others are severely decreased and null phenotypes are observed. The effect on mRNA levels is important for the understanding of phenotype-genotype association. Cystic fibrosis (CF) is a lethal autosomal recessive disease with variable clinical presentation. Recently, two CF patients with mild pulmonary disease carrying nonsense mutations (R553X, W1316X) were found to have severe deficiency of mRNA. In the Jewish Ashkenazi CF patient population, 60% of the chromosomes carry a nonsense mutation, W1282X. Patients homozygous for this mutation have severe disease presentation with variable pulmonary disease. The presence of CF transcripts in a group of patients homozygous and heterozygous for this mutation was studied by reverse transcriptase PCR of various regions of the gene. Subsequent hybridization to specific CF PCR probes and densitometry analysis indicated that the CF mRNA levels in patients homozygous for the W1282X mutation are not significantly decreased by the mutation. mRNA levels were compared for patients heterozygous for the W1282X mutation. The relative levels of mRNA with the W1282X, and the delta F508 or the normal alleles, were similar in each patient. These results indicate that the severe clinical phenotype of patients carrying the W1282X mutation is not due to a severe deficiency of mRNA. In addition, the severity, progression, and variability of the pulmonary disease are affected by other, as yet unknown factors.

Digital clubbing is a common sign in cystic fibrosis (CF) and in a variety of other diseases. However, its pathogenesis remains obscure. In diseases other than CF, regression of clubbing has been noted after cure of the underlying disease. The aim of this study was to assess whether clubbing is reversible in CF patients after lung transplantation. Digital clubbing was investigated in 3 CF patients, prior to and after lung transplantation. Distal phalangeal depth (DPD) and interphalangeal depth (IPD) of the index finger were measured using a skinfold caliper, and the DPD/IDP ratio was calculated. The mean DPD/IDP ratio was 1.08 +/- 0.05 prior to transplantation and 1.00 +/- 0.06, 0.96 +/- 0.06, 0.92 +/- 0.04, and 0.89 +/- 0.07 at 3, 6, 12, and 24 months after transplantation, respectively. In all 3 patients, the DPD/IDP ratio was greater than 1 before transplantation. In 2 patients, this ratio decreased to less than 1 within 3 months, and in the third patient within 9 months after surgery. We conclude that digital clubbing is reversible in CF patients who undergo lung transplantation. Regression was usually noted during the first 3 months posttransplantation. This could be explained either by adequate inactivation of a circulating clubbing-inducing molecule by the normal transplanted lungs, or by removal of the diseased lungs in which this presumably causative substance was produced.

The different aspects of the global H1N1 influenza and its complications are currently of great interest. Neurological complications of the disease and its frequency are still unknown. We report a case of an 11-year-old girl who developed Alice in Wonderland syndrome associated with H1N1 influenza. This unique clinical syndrome was previously described in other diseases. The clinician's awareness of the existence of this syndrome in H1N1 influenza might save the child from undergoing extensive diagnostic procedures.

BACKGROUND--The population of Israel consists of immigrants from many different countries. It is not known whether a single nomogram can be used for spirometric values of children of different ethnic descent. METHODS--Spirometry was performed in 753 second or third generation Israeli children (7-14 years) of different ethnic groups. Both parents of 503 of the children were of the same ethnic background. Subjects were allocated to six ethnic groups (European, Iraqi, North African, Indian, Yemenite, and Georgian). RESULTS--Standing height contributed most to the prediction of spirometric values (forced expiratory volume in one second, forced vital capacity), whereas sitting height did not contribute further. Statistical analysis showed significant ethnic differences. The Georgians had higher spirometric values for FEV1 than all the other ethnic groups, and higher FVC values than those of the Yemenite, North African, and Indian groups. FVC was lower among the Indian than all other groups. CONCLUSION--Differences in normal spirometric values were found among second or third generation Israeli children of different ethnic origins. European, North African, Iraqi, and Yemenite children could be characterised by single equation, whereas children of Georgian and Indian descent needed different predicting equations.

The determination of endocrine and exocrine pancreatic function in cystic fibrosis patients is clinically important. Recently, a new non-invasive test, in which pancreatic stimulation by a Lundh meal is followed by sequential serum lipase measurements, was found to be a good indicator of exocrine pancreatic status. Since the Lundh meal also contains glucose, the present study assessed whether it also might be suitable for evaluation of the pancreatic endocrine axis. After an overnight fast, 10 healthy non-diabetic subjects and 14 cystic fibrosis patients ingested a Lundh meal. Glucose, insulin, and C peptide levels were measured at various time intervals following the meal. For purposes of comparison, the oral glucose tolerance test was also performed on the cystic fibrosis patients. All healthy subjects demonstrated an increase in glucose levels post Lundh meal, peaking at 45 min (mean 140±21 mg/dl) and then gradually declining and reaching the normal range at 120 min. Concordant peaks of insulin (46.3±20 IU/ml) and C peptide (5.8±1.5 ng/ml) levels were noted at 60 min. All 14 cystic fibrosis patients had normal basal glucose levels: in 8, the pattern of glucose, insulin, and C peptide post Lundh meal was similar to that of the healthy controls. These 8 patients also had a normal basal glucose levels: in 8, the pattern of glucose, insulin, and C peptide post Lundh meal was similar to that of the healthy controls. These 8 patients also had a normal oral glucose tolerance test, and their hemoglobin A1C levels were within the normal range. The other 6 cystic fibrosis patients demonstrated glucose levels above 200 mg/dl 30–60 min post Lundh meal, and all also had an impaired oral glucose tolerance test. Of these 6, 4 had high levels of hemoglobin A1C. This study demonstrates that the Lundh meal challenges the endocrine pancreas as well as the oral glucose tolerance test. Thus, determination of both exocrine and endocrine pancreatic status can be achieved by a single non-invasive test.

Introduction:The classical doctrine of mass toxicological events provides general guidelines for the management of a wide range of “chemical” events. The guidelines include provisions for the: (1) protection of medical staff with personal protective equipment; (2) simple triage of casualties; (3) airway pro-tection and early intubation; (4) undressing and decontamination at the hos-pital gates; and (5) medical treatment with antidotes, as necessary. A number of toxicological incidents in Israel during the summer of 2005 involved chlo-rine exposure in swimming pools. In the largest event, 40 children were affected. This study analyzes its medical management, in view of theIsraeli Guidelines for Mass Toxicological Events.Methods:Data were collected from debriefings by the Israeli Home Front Command, emergency medical services (EMS), participating hospitals, and hospital chart reviews. The timetable of the event, the number and severity of casualties evacuated to each hospital, and the major medical and logistical problems encountered were analyzed according to the recently described methodology of Disastrous Incident Systematic Analysis Through-Components, Interactions, Results (DISAST-CIR).Results:The first ambulance arrived on-scene seven minutes after the first call. Emergency medical services personnel provided supplemental oxygen to the vic-tims at the scene and en route when required. Forty casualties were evacuated to four nearby hospitals. Emergency medical services classified 26 patients as mild-ly injured, 13 as mild-moderate, and one as moderate, suffering from pulmonary edema. Most children received bronchodilators and steroids in the emergency room; 20 were hospitalized. All were treated in pediatric emergency rooms. None of the hospitals deployed their decontamination sites.Conclusions:Event management differed from the standard Israeli toxico-logical doctrine. It involved EMS triage of casualties to a number of medical centers, treatment in pediatric emergency departments, lack of use of protec-tive gear, and omission of decontamination prior to emergency department entrance. Guidelines for mass toxicological events must be tailored to unique scenarios, such as chlorine intoxications at swimming pools, and for specific patient populations, such as children. All adult emergency departments always should be prepared and equipped for taking care of pediatric patients.

Objectives The aims of this study were to determine the current pancreatic status of the entire cystic fibrosis (CF) population of Israel, to analyze the clinical characteristics of the pancreatic sufficient (PS) patients, and to characterize the correlation between pancreatic status, pancreatitis, and CF genotype. Methods The Israeli CF database includes 505 patients. These patients were defined as being PS or insufficient according to their fecal pancreatic elastase level or by coefficient fat absorption findings. Mutations were categorized as severe (DeltaF508, W1282X, G542X, S549R, N1303K, Q359K/T360K, 405+1G, and 1717) or mild/variable (3849+10 kb, D1152H, G85E, I1234V, R334W, and 5T) based on disease severity in patients carrying these mutations. Age at diagnosis, presenting symptoms, sweat-chloride concentrations, occurrence of pancreatitis, presence of diabetes, and liver disease were recorded. Results One hundred and thirty-nine (27.5%) of the CF patients were PS. None carried two mutations associated with severe disease. Over one third (34%) had normal or borderline sweat tests; 20 of these 139 patients had pancreatitis (14.3%) but none of the 366 pancreatic insufficient patients had it. Four initially PS patients became pancreatic insufficient: conversion followed several events of pancreatitis in three of them. Nasal potential differences were all pathological in 35 tested PS patients. None had either diabetes or liver disease. Conclusions A substantial number of CF patients are PS. All of them carry at least one mild mutation enabling production of a sufficient amount of normal mRNA to maintain exocrine pancreatic function. Pancreatitis occurs only in CF patients who are PS. These patients are at risk of progressing to pancreatic insufficiency.

Background The diagnosis of right heart failure and pulmonary hypertension in cystic fibrosis (CF) patients with advanced pulmonary disease is sometimes difficult on clinical grounds alone. B-type natriuretic peptide (BNP) & N-terminal pro-B-type natriuretic peptide (N-BNP) levels were found to be useful in differentiating heart failure from various pulmonary diseases. However, its level was never measured in CF patients. The aim of this study was to measure N-BNP level in CF patients without heart failure. Methods The study included 49 patients. Of these, 32 had CF and 17 were control subjects who were matched by age and sex variables to the study group. We looked for a correlation between N-BNP and lung function test, genetic profile, height percentiles, and weight percentiles. N-BNP level was measured using an immunoassay that contains polyclonal antibodies that recognize epitopes located in the N-terminal part of proBNP. Results N-BNP level among CF patients without heart failure, after age and sex adjustments, was similar to the control group (Median: 47 pg/ml vs. 38 pg/ml, P = 0.248, interquartile range: 33–99 pg/ml vs. 31–76 pg/ml). A correlation between N-BNP level to age was found in both groups (CF: R = −0.398; P = 0.024, Control: R = −0.054; P = 0.024). There was no correlation between N-BNP level to FEV1, O2 saturation and nutritional status. Among CF patients, eight (25%) had a mildly elevated N-BNP level whereas none was found in the control group (P = 0.038). Conclusion We conclude that N-BNP level among CF patients is similar to the normal population and that it has no correlation to lung function impairment. Therefore, measurement of elevated N-BNP level in CF patients might be a predictor to the development of pulmonary hypertension and heart failure. Pediatr Pulmonol. 2007; 42:699–703. © 2007 Wiley-Liss, Inc.

Rationale The exercise challenge test (ECT) is a common tool to assess exercise-induced asthma (EIA) in school-aged children. EIA has not been explored in the early childhood setting. Objective To assess the existence of EIA in children in this age group. Measurements and main results A 6-min, controlled, free-run test was performed in 55 children (age range, 3 to 6 years old) who were classified into the following groups: 30 children in whom asthma had been previously diagnosed (group A); and 25 children with prolonged coughing (group B). Spirometry measurements were obtained before the run, and at 1, 2, 3, 5, 10, and 20 min after the run. A positive finding of EIA was defined as a 13% decrease from baseline FEV 1 or baseline forced expiratory volume in the first 0.5 s (FEV 0.5 ). The actual duration of each run was age-related (mean [± SD] duration, 4.8 ± 0.8 min). The nadir in indexes occurred after a mean time of 2.98 ± 1.31 min. A positive EIA finding determined by FEV 1 was present in 15 children, and by FEV 0.5 in 34 children. Twenty-six children were from group A, but only 8 children were from group B. Wheezing and/or prolonged expiration were associated with a positive test result in 31 of 34 children. Coughing was frequent in children with both negative and positive ECT findings. Conclusion The present study documents for the first time the presence of EIA in response to a free-run test in early childhood. Our findings suggest that a free-run test for the presence of EIA is suitable, but that the running duration is limited by age. The duration of airflow limitation after exercise is significantly earlier and shorter in young children with asthma compared with older children. FEV 0.5 is a better index than the traditional FEV 1 for describing positive ECT results in young children. The association of wheezing and/or prolonged expiration may help in defining EIA in early childhood in the absence of a spirometer.

Arginine vasopressin was found in experimental and clinical studies to have a beneficial effect in cardiopulmonary resuscitation. The American Heart Association 2000 guidelines recommended its use for adult ventricular fibrillation arrest, and the American Heart Association 2005 guidelines noted that it may replace the first or second epinephrine dose. There is little reported experience with arginine vasopressin in cardiopulmonary resuscitation of children. Terlipressin, a long-acting analog of arginine vasopressin, has recently emerged as a treatment for vasodilatory shock in both adults and in children, but evidence of its effectiveness in the pediatric setting is sparse. The objective of this retrospective study is to describe our experience in adding terlipressin to the conventional protocol in children with cardiac arrest.Retrospective case series study.An 18-bed pediatric critical care department at a university-affiliated tertiary care children's hospital.Seven pediatric patients with asystole, aged 2 months to 5 yrs, who experienced eight episodes of refractory cardiac arrest and did not respond to conventional therapy.Addition of terlipressin to epinephrine during cardiopulmonary resuscitation of children.Return of spontaneous circulation was monitored and achieved in six out of eight episodes of cardiac arrest. One patient died 12 hrs after return of spontaneous circulation, and four patients survived to discharge with no neurologic sequelae.The combination of terlipressin to epinephrine during cardiopulmonary resuscitation may have a beneficial effect in children with cardiac arrest. More studies on this drug's safety and efficacy in this setting are mandated.

The treatment of acute pain and anxiety in children undergoing therapeutic and diagnostic procedures in the emergency department has improved dramatically over the last few years. The availability of noninvasive monitoring devices and the use of short-acting sedative and analgesic medications enable physicians to conduct safe and effective sedation and analgesia treatment. In today's practice of pediatric emergency medicine, sedation and analgesia has been considered as the standard of care for procedural pain. The following article describes the basic principles of pediatric procedural sedation and analgesia in the emergency department.

Several studies have shown a linear correlation between nutritional status and pulmonary function in patients with cystic fibrosis. Our study aims were: 1) To evaluate the effect of nutritional supplementation via gastrostomy on nutritional, clinical, and pulmonary parameters, and 2) To identify predicting factors for success of long-term nutritional rehabilitation.Twenty-one Israeli patients, aged 8 months to 20 years, underwent gastrostomy insertion from 1992 to 2001. All patients were pancreatic insufficient, and all carried severe mutations (W1282X in 62% of the patients). Anthropometric and clinical data were obtained for each patient: 0-12 months before and 6-12 months and 18-24 months after gastrostomy placement. Standard deviation scores (SDS) for height, weight, and body mass index as well as percent of height-appropriate body weight were calculated.The mean percent-of-predicted forced expiratory volume in 1 second (FEV1) decreased significantly during the first year of gastrostomy feeding (n = 16), from 44.2% +/- 13.9 to 41% +/- 13.3 (P = 0.05). However, during the second year of therapy (n = 10), a trend toward improvement was observed (from 39.4 +/- 12.1 to 41.4 +/- 16.1). Weight, and BMI z-scores as well as weight percent-of ideal body weight increased significantly. Height z-score for age decreased during the first year (from -1.9 +/- 1.3 to -2.1 +/- 1.4), However, a trend toward improvement was observed during the second year. A significant correlation was found between the change in weight z-score and height z-score during the first (r = 0.488, P = 0.016) and the second (r = 0.825, P0.001) years. There was no difference between compliers and noncompliers regarding height, weight, and BMI either before or after gastrostomy placement. A significant correlation between age at insertion of gastrostomy and improvement in height z-score (r = 0.52, P = 0.016) was observed. Cystic fibrosis related diabetes (n = 8) did not affect the response to supplemental feeding.We observed a trend toward improvement of pulmonary disease during the second year, and a significant improvement in weight, height, and BMI z-scores. Compliance, diabetes, and young age prior to tube insertion did not predict success of nutritional rehabilitation.

Purpose: We compare the efficacy and safety profile of oral midazolam and continuous flow 50% nitrous oxide (N 2 O) for alleviating anxiety and pain during voiding cystourethrography (VCU) in children. Materials and Methods: This prospective, randomized clinical trial study was conducted in the radiology unit of a tertiary care center. Children older than 3 years scheduled for VCU were given either 0.5 mg/kg midazolam orally or continuous flow 50% N 2 O. Main outcomes were degree of anxiety and pain as assessed by the attending nurse and radiologist performing the test using a behavioral anxiety score, a distress score and an overall satisfaction score, side effects and recovery profile. Results: The study included 47 children (89% girls) with a mean age of 6 years (range 3 to 15). There were 24 subjects in the midazolam group and 23 in the N 2 O group. Midazolam and N 2 O provided adequate anxiety and pain relief to perform the examination, yet children given N 2 O required less restraining and experienced a significantly shorter recovery time (29 ± 10 vs 63 ± 25 minutes, p Conclusions: Continuous flow 50% nitrous oxide and oral midazolam are comparably safe and effective in reducing anxiety and distress during VCU in children older than 3 years. However, N 2 O provides a more rapid onset of sedating effect and has a shorter recovery time.

Pulmonary disease is the most frequent cause of morbidity and mortality in cystc fibrosis patients. New techniques such as non-invasive positive pressure ventilation have resulted in prolongation of life expectancy in CF patients with end-stage lung disease.To determine the role of NIPPV in CF patients awaiting lung transplantation.Between 1996 and 2001 nine CF patients (5 females) with end-stage lung disease were treated with bi-level positive airway pressure ventilation in the "spontaneous" mode.The patients' mean age at initiation of BiPAP was 15 years (range 13-40 years) and the mean duration of BiPAP usage was 8 months (range 3-16 months). Four patients underwent successful lung transplantation, three patients died while awaiting transplantation, and the remaining two are still on NIPPV while waiting for transplantation. Patients' body mass index increased significantly (P0.05) during BiPAP therapy (from 16.1 to 17.2 kg/m2). Blood pH, PaCO2, and bicarbonate improved significantly (from 7.31 to 7.38, 90.8 to 67.2 mmHg, and 48.9 to 40.3 mEq/L, respectively). Pulmonary function tests were not affected by BiPAP usage. The patients experienced a significant alleviation in morning headaches and improvement in quality of sleep (P0.003). There were no major complications during BiPAP usage.We demonstrated that long-term NIPPV can stabilize and improve physiologic parameters such as ventilation, arterial blood gases and body mass index, as well as subjective symptoms such as sleep pattern, daily activity level, and morning headaches in CF patients with end-stage lung disease. Further prospectively controlled studies are needed to evaluate the potential of BiPAP therapy and its influence on morbidity and mortality in the post-lung transplantation period.

A 6-year-old boy with partial complex seizures developed recurrent episodes of hyperthermia 2 months after topiramate was introduced into his antiepilepsy drug regimen. Further investigation revealed that the febrile episodes were related to environmental temperature and physical activity. A pilocarpine iontophoresis sweat test showed that the amount of sweat produced by the child was 5% that of age-matched controls. Topiramate discontinuation resulted in the disappearance of febrile episodes and normalization of sweat quantity in repeat sweat testing. Based on this observation and the previous data on zonisamide and isolated case reports on topiramate-related hyperthermia and the effect on sweat production, topiramate was suspected of causing oligohydrosis. A pilot study was carried out involving 13 additional children and young adults (age range 1—37 years) receiving topiramate. All patients were directly questioned regarding symptoms of decreased sweating and heat intolerance, went through a pilocarpine iontophoresis sweat test, and were compared with 14 age-matched controls who went through the sweat test for unrelated reasons. Nine of the patients were found to have reduced sweat quantity on the pilocarpine iontophoresis sweat test (including index case) (mean 0.089 g/30 minutes, SD 0.082; age-matched control: mean 0.21 g/30 minutes, SD 0.06). Eight of them were children (below 16 years). However, only three patients revealed symptoms related to heat intolerance. Topiramate is most likely responsible for decreased sweat production as detected by a pilocarpine iontophoresis sweat test. The effect seems to be more significant in children than in adults. There is a discrepancy between test results and clinical symptoms. Interestingly, oligohydrosis was found to be a relatively common side effect of zonisamide. Both zonisamide and topiramate share a carbonic anhydrase inhibitor activity. The significance of oligohydrosis in hot climates should not be underestimated. Its extent, the role of sweat test prediction, and clinical significance during topiramate treatment should be further estimated. ( J Child Neurol 2003;18:254—257).

The aim of the study was to evaluate long-term pulmonary function tests in pediatric survivors of acute respiratory distress syndrome (ARDS).Observational study based on a telephone poll of retrospectively identified post ARDS children who were hospitalized in a pediatric intensive care unit (PICU) in a general 1200-bed teaching, tertiary, regional referral center for children.Follow-up pulmonary function tests were achieved in only 7 children, with a mean age of 7.3+/-4.3 years (range 3-12) and following 5.6+/-4.3 years after PICU discharge. The etiology for ARDS included: lymphoma (n=2), pneumonia (n=2), aspiration (n=1), petrol ingestion (n=1) and snake envenomation (n=1). The children had been ventilated for 9.4+/-7.3 days and their worst PaO2/FiO2 ratio was 65.1+/-17.0 mm Hg. The follow-up pulmonary functions in all the children was within normal limits except for one child who had mildly reduced DLCO and one who had mild exercise-induced hypoxemia (oxyhemoglobin saturation of 94%). Neither of the two nor the others showed subjective symptoms or clinical physical limitations.Children who survive ARDS apparently enjoy long-term normal pulmonary function. Some, however, may present subclinical dysfunction that persists for many years after the acute episode and evoked only by sophisticated lung tests.

Acute respiratory distress syndrome is a well-recognized condition resulting in high permeability pulmonary edema associated with a high morbidity.To examine a 10 year experience of predisposing factors, describe the clinical course, and assess predictors of mortality in children with this syndrome.The medical records of all admissions to the pediatric intensive care unit over a 10 year period were evaluated to identify children with ARDS. Patients were considered to have ARDS if they met all of the following criteria: acute onset of diffuse bilateral pulmonary infiltrates of non-cardiac origin and severe hypoxemia defined by200 partial pressure of oxygen duringor = 6 cm H2O positive end-expiratory pressure for a minimum of 24 hours. The medical records were reviewed for demographic, clinical, and physiologic information including PaO2/forced expiratory O2, alveolar-arterial O2 difference, and ventilation index.We identified 39 children with the adult respiratory distress syndrome. Mean age was 7.4 years (range 50 days to 16 years) and the male:female ratio was 24:15. Predisposing insults included sepsis, pneumonias, malignancy, major trauma, shock, aspiration, near drowning, burns, and envenomation. The mortality rate was 61.5%. Predictors of death included the PaO2/FIO2, ventilation index and A-aDO2 on the second day after diagnosis. Nonsurvivors had significantly lower PaO2/FIO2 (116 +/- 12 vs. 175 +/- 8.3, P0.001), and higher A-aDO2 (368 +/- 28.9 vs. 228.0 +/- 15.5, P0.001) and ventilation index (43.3 +/- 2.9 vs. 53.1 +/- 18.0, P0.001) than survivors.Local mortality outcome for ARDS is comparable to those in tertiary referral institutions in the United States and Western Europe. The PaO2/FIO2, A-aDO2 and ventilation index are valuable for predicting outcome in ARDS by the second day of conventional therapy. The development of a local risk profile may allow early application of innovative therapies in this population.

A deletion mutation of 8.6Kb in the CFTR gene, spanning the exons 17a, 17b and 18 was identified in 4 homozygous unrelated Palestinian CF patients. The patients were of various ethnic subgroups including Muslims, Christians and Druze. The deletion breakpoint occurred within an identical 4bp sequence in introns 16 and 18, and the mutation was defined as 3120+1Kbdel8.6Kb. A simple PCR based assay was designed and using this assay two compound heterozygote patients with the 3120+1Kbdel8.6Kb were identified. The 3120+1Kbdel8.6Kh hearing chromosomes had a common intragenic haplotype and variable flanking polymorphic markers, indicating that it is an ancient founder mutation.

OBJECTIVE The aim of this study was to assess parental reliability in estimating child body weight in emergency situations, when weighing the child is often impossible. METHODS 312 parents were asked to complete an anonymous questionnaire that included estimating their child's weight. 233 questionnaires were enrolled in the study and were assessed statistically using Students t test, and chi2 and ANOVA tests. RESULTS 51.5% of parents estimated their child's body weight within +/-5% of the true weight, 73.4% within +/-10%, and 87.5% within +/-20%. A significant difference was found between paternal and maternal estimations, with 56% of mothers and only 40.3% of fathers estimating within a 5% range of accuracy (P < 0.05). CONCLUSIONS Parents, especially mothers, can estimate their child's body weight within clinically acceptable limits. These estimations can reliably be used to calculate drug doses in prehospital and emergency department situations, when children's weight is not known and cannot be measured.

Objective. The aim of this study was to define the role of possible risk factors for the development of cystic fibrosis (CF)-related liver disease and to analyze the association between liver disease and the different genotypes present in the Israeli CF patient population. Patients and Methods. All patients followed at the seven CF centers in Israel were included in this study. Liver disease was determined by persistently elevated serum liver enzymes and/or bilirubin, and/or significant ultrasonographic changes suggestive of chronic liver disease. The following clinical parameters were evaluated: ethnic origin, age at assessment of liver function, sex, history of meconium ileus, pancreatic function, history of distal intestinal obstruction syndrome, pulmonary function, and cystic fibrosis transmembrane conductance regulator mutation analysis. Results. Of the 288 patients screened, 80 (28%) had liver disease. Of the 256 patients with pancreatic insufficiency, 80 (31%) had liver disease compared with none of the 32 patients with pancreatic sufficiency. Genotype-phenotype correlation was performed on 207 patients carrying identified mutations that were previously classified according to phenotype severity. Liver disease was found in 56 (32%) of 173 patients carrying mutations associated with a severe phenotype and in 6 (38%) of 16 patients carrying at least one mutation associated with a variable genotype (G85E and/or 5T allele). None of the 18 patients carrying the 3849+10kb C->T mutation had liver disease. Prevalence of liver disease increased with age. No correlation was found between liver disease and severity of lung disease, nutritional status, history of meconium ileus, or distal intestinal obstruction syndrome. Conclusion. CF patients who have pancreatic insufficiency and carry mutations associated with a severe or a variable genotype are at increased risk to develop liver disease.

Background The clinical literature on the indicence and subsequent mortality of asthma has come primarily from the experience of large tertiary referral centers, particularly in Western Europe and North America. Consequently, very little has been published on the incidence, management, and outcome of asthma in smaller, community-based intensive care units. Objective The purpose of this study was to explore the course and outcome of children with acute severe asthma treated within a community hospital PICU compared with those described in the literature from larger tertiary referral centers. Design A retrospective analysis of 49 asthmatic children admitted to the Pediatric Intensive Care Unite (PICU) over a 10-year period was performed. Measurements and results The mean age was 5.2 years (range 2 months to 16 years), and the male:female ratio was 3:1. Duration of symptoms prior to admission to hospital was less than 24 hours in 60.4% of the patients. The majority of patients was not treated with either inhaled or oral steroids before admission. Drugs used in the PICU included nebulized beta 2 -agonists, theophylline, steroids, intravenous salbutamol, and intravenous isoproterenol. Although a pharmacologic approach was successful in the majority of patients, intubation and mechanical ventilation were necessary for progressive hypercapnea, exhaustion, and cardiorespiratory arrest in 11/49 of these patients. The average stay in the ICU for our patient group was 2.4 days. Intubated patients had a mean average stay of 3.5 days. Two patients had pneumothorax related to positive pressure ventilation, requiring chest tube insertion for drainage. There were no deaths among the 49 patients admitted to our PICU. Conclusions These data show that for acute severe asthma, outcome is comparable in a community PICU to a tertiary referral institution. We conclude that early ICU admission along with close monitoring is important in reducing morbidity and mortality in children with severe asthma.

We report four patients with cystic fibrosis and fulminant Clostridium difficile-associated colitis: two died, and one required hemicolectomy. Three of four patients carried the N1303K mutation. Severe and fatal C. difficile colitis can occur in cystic fibrosis patients, possibly with a genotype-specific predilection (i.e., N1303K/other). Because cystic fibrosis patients may have a wide spectrum of gastrointestinal symptoms, disease caused by C. difficile must be considered when these patients have acute abdominal pain, diarrhea, or severe leukocytosis.

The syndrome of infantile bronchiolitis in cystic fibrosis (CF) carries a high mortality. Fifteen cases of CF encountered over the past 19 years with severe bronchiolitis with onset during the first 6 months of life are described. Treatment include steroids in high doses. All patients recovered. Further progress resembled the usual natural course of CF and showed no evidence of persisting lung damage. The mechanism of this syndrome is not clear and is probably dependent on many factors involved in early lung disease in CF. The frequency of severe bronchiolitis in cystic fibrosis may not be high, but it continues to be seen in clinical practice today.

A 28-year-old female with cystic fibrosis presented with nephrotic syndrome and progressive renal failure. In addition, she complained of blurred vision and there was a purpuric skin eruption localized to her legs. A renal biopsy revealed fibrillary glomerulonephritis. Skin biopsy demonstrated swelling of capillary endothelium, thickening of arteriolar walls and deposition of IgA, C3 and fibrinogen by immunofluorescence. Opthalmoscopy and fluorescein angiography disclosed cotton wool spots with intraretinal haemorrhages and ischaemia of the macula. Albumin infusions resulted in worsening of eye symptoms and signs. The presence of these three clinicopathologic entities in a patient with CF may indicate the possibility of systemic involvement related to continued exposure to chronic bacterial lower lung infection.

The splicing variant, 5T allele, in intron 8 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene was shown to be associated with partial penetrance of the clinical expression. This splicing variant leads to two possible transcripts: one normal and the other aberrantly spliced that lacks exon 9. The aim of this study was to analyze the molecular basis of the partial penetrance in individuals carrying the 5T allele. We analyzed the level of the correctly spliced RNA transcribed from the 5T allele in nasal and epididymal epithelium and correlated it with disease expression. Semiquantitative nondifferential reverse-transcriptase-PCR showed a considerable variability (6%-37%) in the total level of correctly spliced RNA transcribed from the 5T allele in nasal epithelium from 11 patients. A significant nonlinear correlation (r = .82, P = .002) between the level of the normal CFTR transcripts and the severity of lung disease was shown. No individuals with normal lung function and minimal or no lung disease (FEV1 >80% predicted) had 80%. The level of normal transcripts in epididymal epithelial cells from four infertile males with congenital bilateral absence of the vas deferens was low (6%-24%). In infertile males with normal lung function the level of correctly spliced transcripts in the nasal epithelium was higher than the level in the epididymal epithelium. These results indicate that there is variability in the efficiency of the splicing mechanism, among different individuals and between different organs of the same individual. This variability provides the molecular basis of the partial penetrance of cystic fibrosis disease in patients carrying the 5T allele.

Recently a few cystic fibrosis (CF) patients with borderline or normal sweat tests have been reported. These patients present a diagnostic challenge. We aimed to study the sweat Cl/Na ratio in cystic fibrosis patients and to assess whether this ratio could be used as a diagnostic criteria. The mean sweat Cl/Na ratio of 3 groups was compared: Group A: 71 CF patients carrying 2 mutations known to be associated with severe disease presentation (delta F508, W1282X, G542X, N1303K, 1717-1G --A). Group B: 10 compound heterozygous patients who carry one mutation associated with mild clinical disease (3849 + 10 kb --T). Group C: 142 normal subjects. Sweat chloride levels higher than those of sodium were found in 96% of patients in Group A as compared to 3% of patients in Group C. In Group B 40% of the patients had sweat chloride levels higher than or equal to sodium levels. The mean Cl/Na ratio of Group A (1.2 +/- 0.1) differed significantly from that of Group B (0.94 +/- 0.1) and both groups had significant higher mean Cl/Na ratio compared to Group C (0.7 +/- 0.4) (P0.001). Thus in individuals with a borderline sweat test and a Cl/Na ratioor = 1 the diagnosis of CF should be considered. However, a Cl/Na ratio1 does not exclude CF, since patients carrying mild mutations may have sweat sodium levels higher than those of chloride. Our findings suggest that the sweat Cl/Na ratio in CF is genetically determined and it may be of help in establishing the diagnosis of CF in patients with a borderline sweat test.