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Background and purpose — Low bone mineral density (BMD) may jeopardize the initial component stability and delay osseointegration of uncemented acetabular cups in total hip arthroplasty (THA). We measured the migration of uncemented cups in women with low or normal BMD. Patients and methods — We used radiostereometric analysis (RSA) to measure the migration of hydroxyapatite-coated titanium alloy cups with alumina-on-alumina bearings in THA of 34 female patients with a median age of 64 (41–78) years. 10 patients had normal BMD and 24 patients had low systemic BMD (T-score ≤ −1) based on dual-energy X-ray absorptiometry (DXA). Cup migration was followed with RSA for 2 years. Radiographic follow-up was done at a median of 8 (2–10) years. Results — Patients with normal BMD did not show a statistically significant cup migration after the settling period of 3 months, while patients with low BMD had a continuous proximal migration between 3 and 12 months (p = 0.03). These differences in cup migration persisted at 24 months. Based on the perceived risk of cup revision, 14 of the 24 cases were “at risk” (proximal translation of 0.2 to 1.0 mm) in the low-BMD group and 2 of the10 cases were “at risk” in the normal-BMD group (odds ratio (OR) = 8.0, 95% CI: 1.3–48). The radiographic follow-up showed no radiolucent lines or osteolysis. 2 cups have been revised for fractures of the ceramic bearings, but none for loosening. Interpretation — Low BMD contributed to cup migration beyond the settling period of 3 months, but the migrating cups appeared to osseointegrate eventually.

SummaryBackground The incidence of parapneumonic empyema in children has increased worldwide, but the long-term anatomical and functional consequences in the lungs after empyema are not known. Methods We investigated the long-term outcome of childhood empyema in 26 patients by physical examination, chest radiograph and magnetic resonance image (MRI) of the lungs, and pulmonary function tests. Results At follow-up 3–19 years (mean 8 years) after empyema, all patients had normal findings in the physical examination. Spirometry was normal in 80% of patients, and evidence of obstructive airway disease was detected in 16%. Thirty-six percent of patients had abnormal findings in the chest radiograph and 92% in the MRI of the lungs. In six patients, the MRI revealed significant pleural scarring (extension longer than 1 cm). Thirteen patients (50%) reported persistent respiratory symptoms, such as impaired tolerance of physical activity or prolonged cough after a common cold. During the follow-up four patients suffered a second pneumonia. Conclusions The long-term recovery of children with parapneumonic empyema is good, since most patients subsequently have normal lung function, chest radiograph, and clinical recovery. Half of the patients reported subjective respiratory symptoms and most patients had minor lung abnormalities, mostly pleural scars, detected in the MRI many years after empyema. However, as long-term impairment of lung function was rarely found, the clinical significance of the anatomical residues seen in the lung MRI seems to be minor. Pediatr Pulmonol. 2014; 49:1020–1027. © 2013 Wiley Periodicals, Inc.

The impact of kinematic MRI (KINE-MRI) in the patellofemoral instability and anterior knee pain of the adolescents is rarely reported. Our special interest was to evaluate the patellofemoral joint biomechanics with KINE-MRI in adolescents with affected and unaffected knees in a case–control study. KINE-MRI was performed in 29 adolescents (affected knee group, n = 29 and unaffected knee group, n = 26) aged 11–16 years with unilateral patellofemoral instability. For the control group, we enrolled ten healthy age- and sex-matched volunteers (healthy knee group, n = 19). The study parameters, bisect offset, lateral patellar displacement, patellar tilt angle, sulcus angle and Insall–Salvati ratio at 0, 10, 20 and 30° of flexion–extension, were measured for the affected knee patients (n = 29), unaffected knee patients (n = 26) and the healthy knee subjects (n = 19). The affected knee and the healthy knee subjects had a significant difference in the bisect offset ratio, lateral patellar displacement test and patellar tilt angle test. In these parameters, the difference between the affected knee patients and the healthy knee subjects progressively increased towards the full extension of the knee. In the affected knee and unaffected knee patients, bisect offset ratio at 0° ranged between 0.50 and 1.20 in both groups, whereas the bisect offset ratio in the healthy knee subjects ranged between 0.33 and 0.75 (p

The present eye-movement study assessed the effect of expertise on eye-movement behaviour during image perception in the medical domain. To this end, radiologists, computed-tomography radiographers and psychology students were exposed to nine volumes of multi-slice, stack-view, axial computed-tomography images from the upper to the lower part of the abdomen with or without abnormality. The images were presented in succession at low, medium or high speed, while the participants had to detect enlarged lymph nodes or other visually more salient abnormalities. The radiologists outperformed both other groups in the detection of enlarged lymph nodes and their eye-movement behaviour also differed from the other groups. Their general strategy was to use saccades of shorter amplitude than the two other participant groups. In the presence of enlarged lymph nodes, they increased the number of fixations on the relevant areas and reverted to even shorter saccades. In volumes containing enlarged lymph nodes, radiologists’ fixation durations were longer in comparison to their fixation durations in volumes without enlarged lymph nodes. More salient abnormalities were detected equally well by radiologists and radiographers, with both groups outperforming psychology students. However, to accomplish this, radiologists actually needed fewer fixations on the relevant areas than the radiographers. On the basis of these results, we argue that expert behaviour is manifested in distinct eye-movement patterns of proactivity, reactivity and suppression, depending on the nature of the task and the presence of abnormalities at any given moment.

A total of 20 patients with neurofibromatosis 1 (NF1) were screened for NF1-related osteoporosis, and blood samples were collected for isolation of peripheral blood osteoclast progenitors. Patients with NF1 had higher levels of serum bone turnover markers (CTX and PINP) compared to controls. In addition, persons with high bone resorption in vitro on average had high levels of serum CTX. Of the 20 patients with NF1, 15 had low bone mineral density (osteopenia/osteoporosis), but these 15 patients did not have marked risk factors for low bone mineral density. Thus, we recommend screening for osteoporosis to all adult patients with NF1. Our aim was also to characterize the effects of bisphosphonates on NF1 osteoclasts in vitro. NF1 osteoclasts and osteoclasts from healthy controls in vitro were treated with zoledronic acid, alendronate and clodronate. These bisphosphonates caused a marked reduction in the number of normal control osteoclasts in vitro, while only a slight change was observed in the number of NF1 osteoclasts. Ras-inhibitor FTS counteracted this NF1-related insensitivity to zoledronic acid, suggesting that Ras may play a role in this phenomenon.

To explore the possibility to use 1.5 T MRI in imaging of accumulating gadolinium (Gd) into inflamed endocrine pancreas (insulitis), we compared intravenously delivered IL-2-Gd-DTPA and Gd-DTPA (Magnevist®) in phenotypically healthy 12 weeks old female non-obese diabetic (NOD) mice. At 1 to 48 h after the injection mice were sacrificed and the pancreas-to-background ratio was determined using MRI. In addition Gd concentration of the pancreas and plasma were measured. The pancreas-to-plasma ratio of Gd was 25-fold 24 h after the i.v. injection of IL-2-Gd-DTPA. At the same time the pancreas-to-background ratio measured with 1.5T MRI was 1.5-times higher in the NOD mice receiving IL-2-Gd-DTPA than Magnevist ® (271 ± 37 vs. 183 ± 0,1, P = 0.04) indicating that sufficient differences may exist between IL-2-Gd-DTPA accumulating in the pancreas and in the surrounding tissues to support the use of MRI for imaging of pancreatic insulitis.

The advantages and limitations of MRI in lung infections in children have not been well established. This article illustrates the MRI findings in children with pneumonia caused by Mycoplasma pneumoniae, Streptococcus pneumoniae, and other pathogens. Lung parenchymal, pleural, and lymph node abnormalities are well characterized by MRI. Loculation of pleural fluid is detected in children with empyema. Contrast enhancement may be useful in the differentiation of active inflammation from noninflammatory changes. MRI can be particularly useful in the follow-up of children with chronic pulmonary diseases.

Due to the restricted accessibility of pancreatic tissue in living man, direct analysis of the events preceding development of autoimmune changes in the pancreas has been problematic. In vivo imaging of insulitis might markedly increase understanding of the events and timing of the events that are necessary for the progression toward overt type 1 diabetes.To evaluate possibilities to visualize insulitis in man in vivo with positron emission tomography, we studied 12 male patients (age 26 +/- 7 yr) with newly diagnosed type 1 diabetes (duration range 0-7 months) and nine age- and sex-matched healthy controls after an overnight fast using 2-[(18)F]fluoro-2-deoxy-D-glucose and [(11)C]methionine. For definition of the regions of interest, pancreas was localized with magnetic resonance imaging or computed tomography-positron emission tomography.Glucose uptake to the pancreas was markedly higher in the patients with type 1 diabetes than in the healthy controls (22.9 +/- 6.4 vs. 17.8 +/- 6.0 micromol/kg.min, P = 0.039). Glucose uptake to the pancreas of the patients was inversely associated with the duration of diabetes (r = -0.58; P = 0.024), so that in patients with newly diagnosed type 1 diabetes, glucose uptake was higher than in the healthy controls or patients with long duration of diabetes. Methionine uptake to the pancreas of the patients was similar as in the controls (3.7 +/- 1.9 vs. 4.6 +/- 2.4 micromol/kg.min, P = 0.21).In patients with type 1 diabetes, glucose uptake to the pancreas is enhanced at or soon after the time of diagnosis.

The common cold is generally considered to be an upper respiratory tract infection. We studied the lower respiratory tract in 76 otherwise healthy young adults with the common cold. Viral infection was diagnosed in 56 (74%) of the 76 subjects. Rhinovirus was detected in 42 (55%) subjects. Chest radiography (CR) and high-resolution computerized tomography (HRCT) were carried out in 40 subjects on day 7, and pulmonary function testing with bronchodilator challenge was carried out in 36 patients on days 7 and 21 of the study. Clinical examinations were carried out on days 1, 7 and 21. The subjects recorded their symptoms on a diary card for 20 d. The mean duration of cough was 8.4 (SD 6.5) d and that of sputum production 5.9 (SD 6.4) d. No abnormal findings were detected in the lungs on auscultation. CR and HRCT showed no pulmonary changes associated with the common cold. No clinically remarkable increases were seen in peak expiratory flow, forced expiration volume in 1 s or forced vital capacity after bronchodilator challenge on either days 7 or 21. All patients made a clinical recovery without antimicrobial therapy within 21 d. We conclude that the common cold in young otherwise healthy adults is an upper respiratory tract infection and that clinically important abnormalities in the lower respiratory tract are rare.

Background: Pulmonary complications are common in patients with primary hypogammaglobulinemia. Intravenous immunoglobulin replacement therapy has been thought to reduce the occurrence of pulmonary complications, yet they do occur. Objective: The purpose of this study was to evaluate pulmonary abnormalities in 22 patients with primary hypogammaglobulinemia (18 with common variable immunodeficiency, 4 with X-linked agammaglobulinemia) and to conduct a prospective 3-year follow-up study to assess the possible progression of pulmonary abnormalities. Methods: Pulmonary changes were evaluated with use of pulmonary imaging (chest radiographs, high-resolution computed tomography), and pulmonary function testing. Results: High-resolution computed tomography revealed pulmonary abnormalities in 21 patients. Bronchiectasis was present in 16 patients, whereas chest radiographs revealed bronchiectasis in only 3 patients. Pulmonary function testing showed obstruction in 5 patients. A prospective 3-year follow-up was conducted in 14 patients. It showed silent progression of bronchiectasis in 5 of the 14 patients, all of whom were receiving intravenous immunoglobulin replacement therapy and had preinfusion serum IgG concentrations of 5 g/L or more. Conclusions: Pulmonary abnormalities develop in most patients with primary hypogammaglobulinemia. A new finding is that silent and asymptomatic progression of pulmonary changes may occur in patients despite an adequate immunoglobulin replacement therapy. High-resolution computed tomography is the method of choice in monitoring pulmonary changes. (J Allergy Clin Immunol 1999;104:1031-6.)

The value of compression sonography was assessed to reduce the number of phlebographies otherwise necessary when deep venous thrombosis (DVT) is suspected among hospital patients. Compression sonography was used to study 119 prospective hospital patients who were suspected of having DVT of the lower extremity. The results were compared to those by phlebography. There were 44 DVTs detected by phlebography; ten of these were located only in the calf, below the knee. Of the remaining 34 femoropopliteal DVTs 33 were detected by the compression sonography technique. It is concluded that the use of compression sonography for primary investigation of suspected DVT reduces the number of patients who require phlebography to those whose results by compression sonography are negative. In our study, this would have represented a decrease of 28%, corresponding to a reduction of the total diagnostic costs by 10%.

NEMT, Nordic Evaluation of Medical Technology, conducted a study in 1988-89 on the use and diffusion of diagnostic radiology technologies in Denmark, Finland, Iceland, Norway and Sweden, i.e. the Nordic Countries. The study analysed the responses to a questionnaire sent to all Nordic radiology departments. Our findings show a variation from about 500 to nearly 900 radiology examinations per 1000 inhabitants among the Nordic Countries. Some of the differences are explained by unique structural factors of the health care system in each country, even if they all provide comparable public health services. Other differences are explained by variations in medical practice, accessibility to new imaging modalities, and replacement policies. This paper summarizes the results of the study.

Digital subtraction radiography is a sensitive method for imaging changes in pulmonary aeration during the respiratory cycle. The findings of 75 consecutive dynamic pulmonary examinations performed on 49 pediatric patients using this technique were reviewed together with the findings at chest radiography and, in 18 cases, with bronchoscopy. Symmetric diaphragmatic movement and synchronous, homogeneous variation in the attenuation of lung parenchyma indicated normal conditions in 9 (18%) patients. The most common abnormal finding (36 patients) was an asynchronous variation in the attenuation of the lung parenchyma. A greatly diminished or absent variation in attenuation was diagnostic for a serious air passage obstruction in 7 children. Other abnormal findings were a lowered amplitude of diaphragmatic movement, asynchronous diaphragmatic movement and mediastinal shift. In 10 patients (20%) the dynamic study showed parenchymal abnormalities when chest radiography was normal. Bronchoscopy was performed in 4 of these 10 patients and showed abnormalities in each case.

Introduction: The co-existence of osteoporosis (OP) and osteoarthritis (OA) remains obscure. No systematic studies have been carried out to exclude the possibility that especially female osteoarthritic patients selected for cementless total hip arthroplasty (THA) suffer from primary or secondary OP. Methods: A subgroup of fifty-three female patients (average age, 64.7 years) with advanced primary hip OA scheduled for cementless THA were recruited for DXA and laboratory screening. Before surgery, bone mineral density (BMD) of the lumbar spine, the proximal femurs and the distal forearm were measured. The serum concentrations of calcium, 25-hydroxyvitamin D, parathyroid hormone and biochemical markers of bone resorption and formation were determined to exclude secondary OP. Results: The prevalence of OP (T score T score > −2.5) were 28% and 45%, respectively. Statistically, OP was related to patient's age, low BMI, postmenopausal status and not having estrogen replacement therapy. Five patients (9%) had laboratory findings of secondary OP. Two of them were found to have a parathyroid adenoma. The prevalence of vitamin D insufficiency [S-25(OH)D levels ≤50 nmol/l] was 36% (n=19). As a sign of high bone turnover, the patients with reduced BMD values showed significantly increased serum levels of osteocalcin (p=0.049), intact procollagen type I N propeptide (p=0.040) and N-terminal crosslinking telopeptide of type I collagen (p=0.046). The BMC of the femoral necks of the osteoarthritic hips were significantly higher (p

Purpose: Magnetic resonance imaging (MRI) evaluation of pediatric elbow trauma with or without a visible fracture on radiography. Material and Methods: MRI was performed in the acute phase in 25 children with an elbow injury. Nine patients with an elbow effusion only on radiographs and 16 with a fracture or luxation seen on radiographs underwent subsequent MRI. No sedation was used. Results: MRI revealed eight occult fractures (89%) in seven out of nine patients who had only an effusion on radiographs. Based on MRI findings, septic arthritis was suspected in one patient. Two patients out of five with a supracondylar fracture on the radiograph had a cartilage lesion in the humerus. MRI depicted a 3-mm gap on the articular surface in two patients with a lateral condyle fracture, a more accurate fracture location in two patients than the radiographs, and an additional occult fracture in two patients. MRI showed a fracture not seen on radiographs in two of three patients with prior luxation. Conclusion: MRI is a sensitive and accurate method in the diagnosis of pediatric elbow injuries, especially when only an effusion is present on radiographs. Occult fractures are more common in pediatric patients with elbow injury than reported earlier.

Dynamic Chest Image Analysis aims to develop model-based computer analysis and visualization methods for showing focal and general abnormalities of lung ventilation and perfusion based on a sequence of digital chest fluoroscopy frames collected with the Dynamic Pulmonary Imaging technique. We have proposed and evaluated a multiresolutional method with an explicit ventilation model based on pyramid images for ventilation analysis. We have further extended the method for ventilation analysis to pulmonary perfusion. This paper focuses on the clinical evaluation of our method for perfusion analysis. Three clinical cases are included to illustrate the effects of contrast media in perfusion analysis and a dozen clinical cases without using contrast media are used for evaluation. Our clinical evaluation shows that our method is effective for pulmonary embolism, demonstrating consistent correlations with computed tomography (CT) and nuclear medicine (NM) studies. This performance is the consequence of the idea that the cardiac information recorded in the perfusion image sequence may be utilized to accelerate pulmonary perfusion analysis and improve its sensitivity in detecting pulmonary embolism.

Purpose: to study the changes in pharyngeal behavior after laser uvulopalatopharyngoplasty (LUPPP). Material and Methods: the dynamic changes in the upper airway size were evaluated with digital fluoroscopy in 24 patients with obstructive sleep apnea (OSA) before and after LUPPP and in 16 normal controls, while they were awake and breathing normally. Cephalometric measurements were also made. the patients were classified into the categories of good and poor responders by means of a static-charge-sensitive bed. Results: Following LUPPP, collapsibility at the velopharyngeal level was within the normal range in 15 of 17 good responders, but only in 2 of 7 poor responders (p=0.0086). the minimum airway size at the same level showed a similar trend. in 3 of 7 poor responders the hyoid bone was positioned more caudally than in the good responders (p=0.017). Conclusion: Digital fluoroscopy provides information on the change in upper airway behavior after LUPPP.

We evaluated gallbladder contractility in 58 colicky infants and 57 age-matched controls. Gallbladder size was measured before and 1 h after feeding and the contraction index of the gallbladder was calculated. The results showed decreased contractility of the gallbladder in colicky infants: mean contraction index in colicky infants was 56% (95% confidence interval, 49-63%) and in controls 67% (61-73%). No difference was found in the fasting size of the gallbladder. Postprandial contraction was decreased in colicky infants examined in the evening (n = 14) compared with those examined in the morning (n = 44). Decreased contraction of the gallbladder was found in those colicky infants who presented colicky cry compared with colicky infants without symptoms at the time of examination. No structural abnormalities were found in the general abdominal survey. In conclusion, infants with colic have hypocontractility of the gallbladder. This indicates abnormal biliary tract physiology in association with infantile colic.

Lysinuric protein intolerance (LPI) is an autosomal recessive disease caused by defective transport of the cationic amino acids lysine, arginine, and ornithine at the cell membrane. About 80 patients with LPI have been described worldwide, almost half of them in Finland. The symptoms appear in early childhood as a failure to thrive, growth retardation, muscular hypotonia, and episodes of stupor after protein-rich meals. Twenty-nine Finnish patients (current median age 24.8 years, range 3.7–47.9 years) over a mean follow-up time of 18.1 years (range 1.2–27.2 years) had 57 fractures after minor trauma, mostly in childhood. Their 440 skeletal radiographs showed severe osteoporosis (13/29), controversially abnormal thickening of cortex of the metacarpals (7/29), or thin cortices of the long bones (5/29), endplate impression of vertebrae (8/29), rickets-like metaphyses (2/29), or early destruction of cartilage (3/29). Skeletal maturation was delayed by 1–5 years in 23 of 24 patients. There was no correlation between fracture incidence, radiological bone structure, and delayed skeletal maturation.

Postnatal response of the gall bladder to feeding was studied in 28 preterm infants (gestational age 24-37 weeks) by ultrasonography immediately before feeding and one hour after feeding. Nineteen of the infants were studied once during the first week of life, and nine infants were studied weekly from a postconceptional age of 27-31 until a postprandial gall bladder contraction was seen. A contraction index was calculated as a percentage decrement of the surface area of the gall bladder from its initial value. All preterm infants of more than 33 weeks' gestation showed a gall bladder response to feeding with a contraction index of at least 50%. Very preterm infants (gestational age 27-32 weeks) showed no postprandial gall bladder contraction or the contraction index was under 50%. In a follow up study of nine very preterm infants, the contraction index exceeded 50% at a postconceptional age of 29 to 32 weeks. One infant with prolonged feeding problems had no postprandial gall bladder response before the postconceptional age of 38 weeks. The contraction index increase was dependent on gestational age at birth and on the bolus volume of feeds.

Objective To study bacteria and viruses in maxillary sinuses of patients with primary hypogammaglobulinemia receiving immunoglobulin therapy. Design Prospective cross-sectional study during 6 months. Setting Tertiary care university hospital. Patients Seventeen patients with primary hypogammaglobulinemia (10 males and 7 females; mean age, 39 years [age range, 11-71 years]). Sixteen patients had common variable immunodeficiency, and 1 patient had X-linked agammaglobulinemia. Main Outcome Measures Magnetic resonance imaging and x-ray imaging of paranasal sinuses when patients did not have signs of acute infection and reevaluation 6 months later. Maxillary sinus aspiration and lavage were performed at a follow-up visit. Sinus fluid analysis for bacteria and viruses was performed by culture and by polymerase chain reaction. A questionnaire on symptoms related to sinusitis was administered during the follow-up period. Results Among 17 patients, 9 (53%) had radiologically defined sinusitis without subjective symptoms at study enrollment. At reevaluation 6 months later, radiological findings remained unchanged in two thirds of the patients. Among 15 patients, bacteria were found in sinus lavage samples from 13 patients, and viruses were found in samples from 7 patients. Eight patients had 2 pathogens or more on bacterial culture. Rhinovirus was identified from sinus lavage samples in 5 patients (33%), enterovirus in 3 patients (20%), and respiratory syncytial virus in 1 patient (7%). Pathogenic bacteria were found in maxillary sinuses of all patients who tested positive for rhinovirus and enterovirus. No fungi were found. During the follow-up period, 6 patients reported mucopurulent drainage. Conclusions Bacteria and viruses were commonly found in maxillary sinuses of patients with primary hypogammaglobulinemia. Yearly evaluation by an ear, nose, and throat surgeon is recommended.

In order to evaluate the functional maturity of biliary tract at birth, repeated ultrasound scannings were carried out in 13 healthy newborn infants. All infants were nursed on breast from the age of 2 hours. The gallbladder was full in all infants immediately after birth (longitudinal ellipsoid surface area 1.02 cm2(0.44) (mean(sd)). No response was found to the first nursing. In 3 infants out of 9 (33%) there was a full respose (100% emptying) during the first day of life, while in 2 (22%) the response was partial (47-88% emptying from the initial volume). In the rest 4 (44%) the gallbladder remained full during the first day of life. One of the infants showed no response during the first 3 days of life. The biliary tract dynamics is highly variable after birth, possibly reflecting functional immaturity.

An animal model of bronchial obstruction was developed to radiologically follow up the development of postobstructive pulmonary changes. The study material consisted of 21 healthy rabbits (New Zealand White) of which 5 animals served as controls. A piece of Surgicel (Ethicon) shaped as a 3 x 3 x 10 mm cylinder was placed endobronchially through a 3-mm bronchoscope. The animals were followed up radiologically and endoscopically during the first 30 min after which the bronchoscope was extracted. Sixteen animals were followed up for at least 4 h and, in 4 animals, the foreign body (FB) was removed after 24 h. During follow-up, total collapse of the lung was observed after 1-4 h in all but 2 animals with obstruction of the main brochus. After extraction of the FB, atelectasis of the respective lung had resolved within 24 h. The animal model developed in the present study seems to be rather physiological resembling the development of pulmonary atelectasis in pediatric patients.

Extraction of a foreign body from the tracheobronchial tree was accomplished for 83 children. The mean age was 1 year 9 months for the 27 girls and 3 years 1 month for the 56 boys; 46 children (55%) were younger than 2 years of age. Sixteen (19%) of the foreign bodies were radiopaque, and 35 (42%) were either verified or suspected radiologically before endoscopy. Forty-one foreign bodies (49%) were situated in the right bronchial tree. Extraction was successful in 81 children (98%) and was performed on 50 children (60%) during the first 24 hours. Twenty-five (30%) of the foreign bodies were peanuts. Three children experienced a residual foreign body, without serious complications. We believe that an open tube bronchoscopy should be performed whenever abnormal stridor or cough is observed in a healthy child and when appropriate antibiotic therapy is unsuccessful.