A pragmatic approach to the radiologic diagnosis of pediatric syndromes and skeletal dysplasias.

This article describes a practical approach to the radiologic evaluation and diagnosis of inherited bone dysplasias and syndromes. Useful references and resource materials are suggested. To illustrate these points, challenge cases are provided. The reader is invited to research each of these examples and arrive at a diagnosis. The correct diagnosis and case discussion follow the figures.

Oestrogen effects in olivo-cerebellar and hippocampal circuits.

17 beta-oestradiol (E2) is known to exert activating effects on CNS excitability, which are in part mediated by increases in glutamate responses, as we have shown in cerebellum. In addition, this steroid is known to facilitate rapid, rhythmic limb movement. Because the inferior olive is believed to be a timer of rapid movement, we have investigated effects of E2 on patterns of discharge recorded from dorsal accessory olive (DAO) using chronically implanted microwires. E2 increases the frequency of rhythmic olivary discharge as well as the number of synchronized neurons in association with facilitation of rhythmic limb and vibrissae movement. One possible mechanism for this effect is via an increase in gap junction proteins, as olivary cells are electrotonically coupled. Levels of connexin 32 (Cx32) and the dendritic lamellar body, both markers for gap junction-associated proteins, are increased threefold after 48 h E2 exposure (2 micrograms, i.p.), compared to control in both ventral medulla and hippocampal neurons. Gap junction conductance has also been shown to be decreased by gamma-aminobutyric acid (GABA)ergic input. For this reason, we tested effects of 48 h E2 treatment on GABAA receptor subunit proteins and GABAergic synaptic current. E2 increased levels of the alpha 4 subunit in hippocampus via an increase in the GABA-modulatory progesterone metabolite 3 alpha-OH-5 alpha-pregnan-20-one. This effect was correlated with a decrease in decay time of tetrodotoxin-resistant miniature inhibitory postsynaptic currents (mIPSCs) recorded from pyramidal cells in CA1 hippocampus, an effect which would tend to reduce total GABA inhibition. In sum, these effects of E2 are consistent with the concept that E2 exerts primarily activating effects on CNS excitability.

Direct measurement of LDL-C in children: performance of two surfactant-based methods in a general pediatric population.

OBJECTIVES: Several pediatric advisory groups have recommended selective screening for dyslipidemia in children. Low-density lipoprotein cholesterol (LDL-C) is measured clinically with the Friedewald calculation in fasting samples. Nonfasting measurement of LDL-C would be clinically useful in children. DESIGN AND METHODS: In the present study, we examine the performance of two surfactant-based direct LDL-C assays in paired samples, fasting and nonfasting, from 100 children. RESULTS: LDL-C in the fasting state was significantly lower with the Friedewald estimation: 2.43 +/- 0. 61 mmol/L, N-geneous (Genzyme Corp.) direct LDL-C: 2.30 +/- 0.59 mmol/L, and Roche (Roche Diagnostics) direct LDL-C: 2.32 +/- 0.57 mmol/L than with ultracentrifugation-dextran-sulfate-Mg(2+) precipitation (UC-DS): 2.47 +/- 0.64 mmol/L. Moreover, there was increased negative bias using nonfasting samples with N-geneous: 2. 25 +/- 0.56 mmol/L and Roche: 2.26 +/- 0.56 mmol/L compared with fasting UC-DS. Correlation with US-DS was highest for Friedewald (r = 0.974) and fasting N-geneous (r = 0.973), and lowest with nonfasting N-geneous (r = 0.849) and Roche in fasting (r = 0.891) and nonfasting samples (r = 0.747). The sensitivity at LDL-C concentration of 2.85 mmol/L for the two direct methods when either fasting or nonfasting samples were used, was lower than that obtained with Friedewald. CONCLUSION: Overall, these direct LDL-C assays demonstrated limited utility in screening children but may be useful in the management of lipid disorders.

Back pain in children who present to the emergency department.

The purpose of this study was to identify the causes and epidemiology of back pain in children who present to the emergency department. All children who presented to an urban pediatric emergency department (ED) during a 1-year period with the chief complaint of back pain were examined and evaluated with a uniform questionnaire. This was completed at the time of the ED visit in 48%, and within 48 hours in 52%. During a 1-year period, 225 children with a complaint of back pain were evaluated. The mean age was 11.9 +/- 4 years and 60% were female. Onset was acute (< or = 2 days) in 59%, and chronic (> or = 4 weeks) in only 11.6%. Pain awakened children from sleep in 47%, and caused 52% to miss school or work. The most common diagnoses were direct trauma (25%), muscle strain (24%), sickle cell crises (13%), idiopathic (13%), urinary tract infection (5%), and viral syndrome (4%). Radiographs of the back were rarely helpful. About 5% required hospital admission; one half of these were attributed to sickle cell crises. We conclude that back pain is an uncommon reason for children to present to an emergency department. When present, pediatric back pain is most often musculoskeletal, associated with an acute infectious illness or a traumatic event. Although the etiology is rarely serious, back pain often affects the daily activities of symptomatic children.

Real-time control of a robot arm using simultaneously recorded neurons in the motor cortex.

To determine whether simultaneously recorded motor cortex neurons can be used for real-time device control, rats were trained to position a robot arm to obtain water by pressing a lever. Mathematical transformations, including neural networks, converted multineuron signals into 'neuronal population functions' that accurately predicted lever trajectory. Next, these functions were electronically converted into real-time signals for robot arm control. After switching to this 'neurorobotic' mode, 4 of 6 animals (those with > 25 task-related neurons) routinely used these brain-derived signals to position the robot arm and obtain water. With continued training in neurorobotic mode, the animals' lever movement diminished or stopped. These results suggest a possible means for movement restoration in paralysis patients.

Identification of the Chinese IVS-II-654 (C-->T) beta-thalassemia mutation in an immigrant Turkish family: recurrence or migration?

In this study we describe the Chinese IVS-II-654 (C-->T) beta-thalassemia mutation for the first time in an immigrant Turkish family living in Istanbul and originating from Xanthe, Greece. Four members of the family, representing 3 generations, are heterozygous for this mutation. A detailed family history demonstrated a Greek origin for members of 5 generations with no records of migration or consanguineous marriages. Analysis of polymorphic nucleotides located at the 5' end of the beta-globin chromosomes bearing the IVS-II-654 mutation in the family described carried the (AT)9(T)5 type of microsatellite sequence and the ACATCCCCA haplotype. These 2 haplotype components favor a non-Eastern Asian origin for this chromosome, hence suggesting an independent origin for the IVS-II-654 mutation described in this family.

Phenotype of the fibroblast growth factor receptor 2 Ser351Cys mutation: Pfeiffer syndrome type III.

We present a patient with pansynostosis, hydrocephalus, seizures, extreme proptosis with luxation of the eyes out of the lids, apnea and airway obstruction, intestinal non-rotation, and severe developmental delay. His skeletal abnormalities include bilateral elbow ankylosis, radial head dislocation, and unilateral broad and deviated first toe. The phenotype of this patient is consistent with that previously reported in Pfeiffer syndrome type III, but is unusual for the lack of broad thumbs. Our patient most closely resembles the case described by Kerr et al. [1996: Am J Med Genet 66:138-143] as Pfeiffer syndrome type III with normal thumbs. Mutations in the genes for fibroblast growth factor receptors (FGFR) 1 and 2 have previously been seen in patients with Pfeiffer syndrome type I. The mutation identified in our patient, Ser351Cys in FGFR2, represents the first reported cause of Pfeiffer syndrome type III. An identical mutation was described once previously by Pulleyn et al., in a patient whose brief clinical description included cloverleaf skull, significant developmental delay, and normal hands and feet [Eur. J. Hum. Genet. 4: 283-291, 1996]. In our patient, previously performed single-strand conformation polymorphism analysis failed to detect a band shift; the mutation was identified only after independent sequence analysis.

The effects of congenital heart disease on the lungs.

The alterations in anatomy and physiology, which often accompany congenital heart disease, may have a major impact on the child's lungs. These changes in pulmonary blood flow and ventilation are usually demonstrable on chest radiography and should be recognized as manifestations of the underlying lesion and not mistaken for primary lung disease. Correlation with the clinical history and physical examination are essential for correct interpretation, but radiological findings should be viewed objectively and without bias to provide accurate and valuable information to the treating physician.

Pneumonia in infants and children: radiological-pathological correlation.

The radiographic characteristics of pulmonary infection in children are many and varied. Although typical patterns are helpful in diagnosis, clinical and laboratory evaluation provide important diagnostic information. An understanding of the basic pathophysiology of infection and an appreciation of the anatomy of the child's growing lung help provide clearer, insightful, and more accurate radiological interpretation.

GABA(A) receptor alpha4 subunit suppression prevents withdrawal properties of an endogenous steroid.

The hormone progesterone is readily converted to 3alpha-OH-5alpha-pregnan-20-one (3alpha,5alpha-THP) in the brains of males and females. In the brain, 3alpha,5alpha-THP acts like a sedative, decreasing anxiety and reducing seizure activity, by enhancing the function of GABA (gamma-aminobutyric acid), the brain's major inhibitory neurotransmitter. Symptoms of premenstrual syndrome (PMS), such as anxiety and seizure susceptibility, are associated with sharp declines in circulating levels of progesterone and, consequently, of levels of 3alpha,5alpha-THP in the brain. Abrupt discontinuation of use of sedatives such as benzodiazepines and ethanol can also produce PMS-like withdrawal symptoms. Here we report a progesterone-withdrawal paradigm, designed to mimic PMS and post-partum syndrome in a rat model. In this model, withdrawal of progesterone leads to increased seizure susceptibility and insensitivity to benzodiazepine sedatives through an effect on gene transcription. Specifically, this effect was due to reduced levels of 3alpha,5alpha-THP which enhance transcription of the gene encoding the alpha4 subunit of the GABA(A) receptor. We also find that increased susceptibility to seizure after progesferone withdrawal is due to a sixfold decrease in the decay time for GABA currents and consequent decreased inhibitory function. Blockade of the alpha4 gene transcript prevents these withdrawal properties. PMS symptoms may therefore be attributable, in part, to alterations in expression of GABA(A) receptor subunits as a result of progesterone withdrawal.

The impact of extended radiology attending coverage in a children's hospital.

OBJECTIVE: In order to achieve more "timely" interpretation of radiologic examinations, a 3 to 11 p.m. attending radiologist slot was incorporated into the daily schedule utilizing existing staff. Our purpose was to assess the effectiveness of this practice by measuring report generation times. MATERIAL AND METHODS: Using a radiology information system (DecRAD), the time between completion of the technical examination and dictation of the official report for general (plain film) studies was determined for a 2-month period and compared to similar periods 1 and 2 years prior to instituting extended hours. Emergency and portable (ICU) exams were similarly analyzed. RESULTS: The number of examinations reported within 2 h of technical completion increased by 8.5% (mean); reporting within 4 h increased by 20%; reporting within 6 and 12 h of completion each increased by 24%. Over 80% of cases were dictated within 12 h after the change in practice occurred; whereas, it took up to 24 h in preceding years. Analysis of emergency and portable ICU exams showed similar trends, and the number of next day "call-backs" to the emergency department was significantly reduced. CONCLUSION: By extending attending coverage, more plain film examinations, especially emergency cases and ICU portables, were read and reported within a shorter time providing prompt communication with clinicians and more opportunity to influence management decisions.

Duodenitis in children: correlation of radiologic findings with endoscopic and pathologic findings.

PURPOSE: To determine the accuracy of barium studies in the diagnosis of duodenitis in children. MATERIALS AND METHODS: Seventy-five children (45 boys and 30 girls; mean age, 9 years) underwent upper gastrointestinal (GI) examinations. Twenty-four of the children had biopsy-proved duodenitis, and 51 were healthy control subjects. Radiologic findings were reviewed by two experienced, blinded observers and correlated with endoscopic and histologic results. Duodenal mucosal-fold thickness was measured on spot radiographs (20% magnification), and the extent of disease was evaluated. RESULTS: Of 15 children with mild duodenitis, 13 had normal radiologic findings and 11 had normal findings at esophagogastroduodenoscopy. Of nine children with severe duodenitis, all had friability or ulceration at endoscopy and mucosal-fold thickening of greater than or equal to 4 mm (> or = 3 mm in one infant aged less than 1 year) at upper GI examination. Mucosal-fold thickening was diffuse in patients with celiac, autoimmune, and adenovirus disease and was proximal in patients with peptic ulcer and Crohn disease. Of 51 control subjects, 50 had normal radiologic results, while 47 had normal endoscopic results. The sensitivity of upper GI examination for mild and severe duodenitis combined was 46% with a specificity of 98%, whereas endoscopy had a sensitivity of 54% and specificity of 92%. CONCLUSION: Mucosal-fold thickening was a specific sign of duodenitis in children and should be investigated. Upper GI examination yielded results similar to those at endoscopy.

A database program for the management of staff scheduling in a radiology department.

OBJECTIVE: Our objective is to report how an inexpensive computer database program (Filemaker Pro, version 3.0, for Macintosh) can be used to manage work schedules and optimize staff use in a radiology department. CONCLUSION: Using this report in conjunction with the manufacturer's documentation, one can adapt this database program to any scheduling situation.

Skeletal anomalies and deformities in patients with deletions of 22q11.

Skeletal anomalies in patients with a 22q11.2 deletion are reported infrequently. We report the skeletal findings in 108 patients with a 22q11.2 deletion, of whom 37 (36%) had a skeletal anomaly. Twenty-two patients (20%) had anomalies of the limbs, 7 of the upper limb, including preaxial or postaxial polydactyly. An anomaly of the lower limb was found in 16 patients, including postaxial polydactyly, clubfoot, severely overfolded toes, and 2-3 toe cutaneous syndactyly. Chest films of 63 patients were examined; 30% of them had abnormal findings, most commonly supernumerary ribs (17%) or a "butterfly" vertebral body (11%). Hypoplastic vertebrae, hemivertebrae, and vertebral coronal clefts were also noted. Thus, skeletal anomalies are not uncommon in patients with a 22q11.2 deletion and may occur more frequently than recognized previously.

Further clinical delineation and increased morbidity in males with osteopathia striata with cranial sclerosis: an X-linked disorder?

Osteopathia striata with cranial sclerosis (OS-CS) is a bone dysplasia characterized by hypertelorism, macrocephaly, frontal bossing, broad nasal bridge, palate anomalies, hearing deficits, and mental retardation. The radiographic findings include cranial sclerosis, linear striations in the long bones and iliac wings, small poorly aerated sinuses, scoliosis, and increased bone density. The sensory deficits are disabling, but the condition generally is not life threatening. We describe 4 brothers with the characteristics of OS-CS, 3 of whom have died from more serious complications of the disorder. The mother of these children, and her only daughter, have the mildest phenotype with the typical linear striations in the long bones and macrocephaly. OS-CS is thought to be autosomal dominant with complete penetrance and variable expressivity. Our observations could be consistent with X-linkage, since there is milder expression in the female relatives. In addition, we recognize absent fibulae, malrotation, and omphalocele as new manifestations as well as congenital heart disease.