Pulmonary fibrosis in youth treated with radioiodine for juvenile thyroid cancer and lung metastases after Chernobyl.

PURPOSE: The objective of this project was to systematically determine the prevalence and consequences of pulmonary fibrosis in youth with thyroid carcinoma and lung metastases from Belarus who were treated with radioiodine ((131)I). METHODS: A total of 69 patients treated for juvenile thyroid carcinoma and lung metastasis with (131)I were assessed. A group of 29 patients without lung metastases and prior (131)I treatment served as controls. The assessments included a CT scan of the lungs, extensive pulmonary function testing and an incremental cycle test to volitional fatigue with measurements of oxygen uptake (VO(2)), oxygen saturation and alveolar-arterial difference in oxygen partial pressure (ΔaaO(2)). RESULTS: Five patients with lung metastases showed advanced pulmonary fibrosis on CT scans and also had poorer lung functions compared with the 62 patients with none or minor signs of fibrosis and the 29 controls. Furthermore, these five patients showed lower peak VO(2), lower oxygen saturation at peak exercise and higher exercise ΔaaO(2). They were younger at the time of cancer diagnosis and had received chemotherapy more frequently than youth with pulmonary metastases who did not develop fibrosis. One of the five patients subsequently died from pulmonary fibrosis. CONCLUSION: Following the Chernobyl catastrophe, about 7% of children treated with radioiodine for thyroid carcinoma and lung metastases displayed pulmonary fibrosis which was associated with functional impairments. Based on the characteristics of affected individuals, the number of radioiodine courses may have to be limited, especially in young children, and chemotherapy should be avoided.

Saethre-Chotzen syndrome caused by TWIST 1 gene mutations: functional differentiation from Muenke coronal synostosis syndrome.

The Saethre-Chotzen syndrome (SCS) is an autosomal dominant craniosynostosis syndrome with uni- or bilateral coronal synostosis and mild limb deformities. It is caused by loss-of-function mutations of the TWIST 1 gene. In an attempt to delineate functional features separating SCS from Muenke's syndrome, we screened patients presenting with coronal suture synostosis for mutations in the TWIST 1 gene, and for the Pro250Arg mutation in FGFR3. Within a total of 124 independent pedigrees, 39 (71 patients) were identified to carry 25 different mutations of TWIST 1 including 14 novel mutations, to which six whole gene deletions were added. The 71 patients were compared with 42 subjects from 24 pedigrees carrying the Pro250Arg mutation in FGFR3 and 65 subjects from 61 pedigrees without a detectable mutation. Classical SCS associated with a TWIST 1 mutation could be separated phenotypically from the Muenke phenotype on the basis of the following features: low-set frontal hairline, gross ptosis of eyelids, subnormal ear length, dilated parietal foramina, interdigital webbing, and hallux valgus or broad great toe with bifid distal phalanx. Functional differences were even more important: intracranial hypertension as a consequence of early progressive multisutural fusion was a significant problem in SCS only, while mental delay and sensorineural hearing loss were associated with the Muenke's syndrome. Contrary to previous reports, SCS patients with complete loss of one TWIST allele showed normal mental development.

Oxygen uptake kinetics are slowed in cystic fibrosis.

PURPOSE: There are conflicting reports on the kinetics of oxygen uptake at the onset of exercise in patients with cystic fibrosis (CF). The objective of the present study was, therefore, to compare oxygen uptake (VO(2) kinetics in patients with CF with those of healthy controls (CON). METHODS: Eighteen CF patients (FEV1 37-98% predicted) and 15 CON aged 10-33 yr completed two to four transitions from low-intensity cycling (stage 1, 20 W) to cycling at 1.3-1.4 W.kg(-1) body weight (stage 2). There was no difference between groups in heart rate at stages 1 and 2 or in relative exercise intensity, as expressed as percent VO(2peak) or percentage of ventilatory threshold. However, oxygen saturation (SpO(2)) was lower in the patients with CF during both stages. VO(2) data were interpolated second by second, time-aligned, and averaged. Monoexponential equations were used to describe phase II VO(2) responses. RESULTS: Although there were no differences between CF and CON in amplitude (10.9 +/- 1.8 vs 10.2 +/- 1.6 mL O2.W(-1)) of phase II VO(2) response, the time constant tau was significantly prolonged in CF compared with CON (36.8 +/- 13.6 vs 26.4 +/- 9.1 s). When tau was adjusted for the effects of FEV1 or SpO(2) during submaximal exercise, the difference between CF patients and controls disappeared. CONCLUSION: VO(2) kinetics are slowed in CF, which may, in part, be attributed to an impairment of oxygen delivery.

Diagnosis of vesicoureteric reflux with low-dose contrast-enhanced harmonic ultrasound imaging.

BACKGROUND: Harmonic US imaging has been shown to be better than conventional US for the detection and visualisation of microbubbles in contrast-enhanced voiding urosonography (VUS). OBJECTIVE: To determine the diagnostic efficacy of VUS using a reduced dose of the US contrast medium in comparison to voiding cystourethrography (VCUG). MATERIALS AND METHODS: Fifty-five children (17 boys, 38 girls; mean age 4 years) were recruited. All patients underwent VUS by harmonic imaging followed by VCUG. The dose of the US contrast medium (Levovist) administered intravesically was half of the recommended dose i.e. 5% of the bladder filling volume. RESULTS: A total of 114 kidney-ureter (K-U) units were available for evaluation. Vesicoureteric reflux (VUR) was detected in 29 K-U units by one or both examination modalities. There was a 91.2% concordance rate between VUS and VCUG. VUR in seven and three K-U units were detected only by VUS and VCUG, respectively. Taking VCUG as the reference method, VUS had the following diagnostic results: 86.4% sensitivity, 92.4% specificity, positive and negative predictive values of 73.1 and 96.6%, respectively. CONCLUSIONS: Even when the dose of US contrast medium is halved, the diagnostic efficacy of harmonic VUS is comparable to VCUG. Consequently, we recommend an US contrast medium dose of 5% of the bladder filling volume for the diagnosis of VUR using contrast-enhanced harmonic VUS.

Intrarenal reflux: diagnosis with contrast-enhanced harmonic US.

The objective of this case report is to demonstrate the possibility of visualizing intrarenal reflux (IRR) in children using contrast-enhanced harmonic voiding urosonography (VUS). A 10-month-old girl underwent VUS as part of the work-up of acute pyelonephritis of the right kidney. Before and after intravesical administration of US contrast medium (Levovist) the urinary tract was scanned in harmonic imaging mode. Bilateral vesicoureteric reflux was detected (right grade IV, left grade III). Moreover, at the height of the reflux the right kidney parenchyma turned markedly echogenic, corresponding to massive IRR. The voiding cystourethrography that followed confirmed the results of the VUS.

Ultrasound and MRI features of pyomyositis in children.

Pyomyositis (PM) is an infectious disease of the skeletal muscle with a wide range of symptoms such as pain, fever or swelling, and is predominantly found in the tropics. In recent years PM has increasingly been diagnosed in Europe and in the U.S. Our objective is to describe the ultrasound and MRI features of PM in children. A retrospective analysis of 12 children with PM (2 girls and 10 boys; age range 1-13 years) admitted to our hospital between 1998 and 2002 was carried out. All children had a US exam and 8 children underwent MRI. Children with osteomyelitis and accompanying myositis were excluded from this study. In all patients who had MRI ( n=8) the infected muscles were found to have the following features: hyperintensity on the T2-weighted images, diffuse borders and contrast enhancement. In the pelvis ( n=4), only one PM could be detected with US, in the other 3 cases only US of the hip joint was performed based on the clinical symptoms. In the extremities ( n=8) US always revealed an altered echogenicity of the affected muscles as well as fluid collection in 5 cases. Both US and MRI reveal characteristic changes of the PM. Ultrasound should be the first imaging modality in the extremities. In the pelvis MRI is the imaging modality of choice. The MRI is needed to differentiate pyomyositis from osteomyelitis.

Fibrosing mediastinitis with superior vena cava obstruction as the initial presentation of Langerhans' cell histiocytosis in a young child.

We present a 2-year-old girl with an unusual presentation of Langerhans' cell histiocytosis (LCH). Five months prior to admission to our hospital, she received IV steroids for bronchial obstruction. On admission, clinical signs of SVC obstruction were evident and a mediastinal mass was evident on the chest radiograph and MRI. Biopsy revealed fibrosing mediastinitis. Five months later, osteolysis was present on a skull radiograph. Surgical biopsy of the skull lesion revealed LCH. This case is unique because it demonstrates a rare initial manifestation of LCH that has not been previously reported. Furthermore, the primary, solitary mediastinal manifestation without calcifications was histologically interpreted as fibrosing mediastinitis, and the final diagnosis of LCH was only made after identifying the skull lesion.

The pattern of skeletal anomalies in the cervical spine, hands and feet in patients with Saethre-Chotzen syndrome and Muenke-type mutation.

BACKGROUND: Saethre-Chotzen syndrome (SCS) and Muenke-type mutation (MTM) are complex syndromes with craniosynostosis and skeletal anomalies including syndactyly, carpal and tarsal fusions, and cervical spine abnormalities. OBJECTIVE: In this study, we analysed radiographs of the cervical spine, hands and feet of a large patient population with genetically proven SCS and MTM. The aim was to describe the pattern of skeletal anomalies and to determine whether specific features are present that could help differentiate between the two entities. MATERIALS AND METHODS: Radiographs of 43 patients (23 males, 20 females) with SCS (n=35) or MTM (n=8) were evaluated. The median age was 8 years (range 1 month-36 years). All radiographs were reviewed by two radiologists. RESULTS: In the hands and feet, a variety of anomalies such as brachyphalangy, clinodactyly, partial syndactyly, partial carpal or tarsal fusion, and cone-shaped epiphyses were noted. Duplicated distal phalanx of the hallux (n=12/35) and triangular deformity of the epiphysis of the distal phalanx of the hallux (n=10/35) were detected in SCS only; calcaneo-cuboid fusion (n=2/35) was detected in MTM only. In the cervical spine, fusion of vertebral bodies and/or the posterior elements occurred only in patients with SCS. CONCLUSIONS: Pathognomonic signs for SCS are the triangular shape of the epiphysis and duplicated distal phalanx of the hallux. Calcaneo-cuboid fusion was detected in MTM only. These signs may be helpful in the differentiation of SCS from MTM.

B-Cell lymphoproliferative disorder not associated with Epstein-Barr Virus in a child with relapsed acute lymphoblastic leukemia.

Lymphoproliferative disorder (LPD) is described in only a few children receiving chemotherapy for cancer. In all of them, an association between LPD and EBV (Epstein-Barr Virus) was found. We report on a patient who developed LPD not associated with EBV while receiving chemotherapy for relapsed acute lymphoblastic leukemia (ALL). Despite discontinuation of chemotherapy, administration of intravenous immunoglobulins and surgery the patient died. Growing experience with this disorder may allow better treatment options in the future and will show whether LPD not associated with EBV requires different therapeutic strategies.

Bilateral cystic adenomatoid lung malformation type III--a rare differential diagnosis of pulmonary hypertension in neonates.

UNLABELLED: Congenital cystic adenomatoid lung malformation (CCAM) is a rare disorder characterized by replacement of normal pulmonary tissue with cysts of variable size and distribution. Only sporadic cases of CCAM type III have been described that were stillborn or died in the early neonatal period. To our best knowledge we report the first infant with bilateral CCAM type III that was not ventilator-dependent for the first 10 weeks of life and survived until the age of 5 months. Postnatally the newborn presented with signs of only mild respiratory distress and chest radiograph did not show evidence of cystic lesions. In the following weeks the major clinical symptom was persistent pulmonary hypertension with severe tachypnea, O2 requirement and CO2 retention. Pulmonary hypertension did not respond to HFOV ventilation, NO ventilation or prostacyclin inhalations. CONCLUSIONS: (1) Persistent pulmonary hypertension can be a major clinical feature in neonates with bilateral CCAM type III. (2) A normal chest X-ray does not exclude the possibility of bilateral type III CCAM. (3) Computerized tomography appears to be superior to conventional chest X-ray imaging in detection of small cystic lesions in infants with CCAM type III. (4) In cases of prenatally suspected CCAM type III, parents should be informed that short-term survival is possible.

Clinical manifestations and diagnosis of invasive aspergillosis in immunocompromised children.

UNLABELLED: Invasive aspergillosis (IA) is a serious life-threatening complication in immunocompromised children. The commonest risk groups are children with acquired immunodeficiency syndrome, leukaemia, corticosteroid and other immunosuppressive therapy, chronic granulomatous disease and severe combined immunodeficiency as well as neonates. The clinical manifestations are heterogeneous and many organ systems can be involved. Diagnosis based on the clinical presentation alone is cumbersome. Innovative and sensitive laboratory test systems which detect fungal antigens or DNA in clinical specimens have been recently developed. Specific Aspergillus antibody detection using recombinant antigen technique has also been introduced. Although each individual technique has drawbacks, the combined use of culture with antigen and antibody ELISA as well as PCR should result in an earlier and more definitive diagnosis of IA in children presenting with clinical and/or radiological signs of aspergillosis. In high risk children these methods are valuable for serial screening and early detection of Aspergillus infection. The implementation of accurate diagnostic criteria and standardised diagnostic flow charts in children at risk will lead to a better outcome of IA in the future. CONCLUSION: definite, well-timed early diagnosis and sufficient therapy is elementary for a successful outcome of invasive aspergillosis in immunocompromised children. To date, the diagnosis of invasive aspergillosis remains a combination of clinical presentation, radiology and microbiological tests.

Diagnostic imaging of vesicoureteral reflux.

The diagnostic imaging modalities for vesicoureteral reflux in children comprise both radiologic and sonographic methods. The radiologic methods are voiding cystourethrography and radionuclide cystography. Voiding cystourethrography is the commonest imaging modality for reflux. With the introduction of pulsed fluoroscopy the radiation exposure of this examination is significantly curtailed. It is the imaging of first choice of the urethra. Various sonographic methods of reflux examination had been tried in the past. The real breakthrough came with the availability of stabilized US contrast media. The diagnostic accuracy of contrast-enhanced voiding urosonography has been found to be comparable to the radiologic methods. With the emergence of harmonic imaging the potential for significant improvement of the sonographic method has been achieved. Voiding urosonography is primarily performed in follow-up studies and as the first reflux examination in girls.