Transcutaneous immunotherapy via laser-generated micropores efficiently alleviates allergic asthma in Phl p 5-sensitized mice.

BACKGROUND: Specific immunotherapy via the subcutaneous or oral route is associated with local and, in some cases, systemic side effects and suffers from low patient compliance. Due to its unique immunological features, the skin represents a promising target tissue for effective and painless treatment of type I allergy. The current study was performed to compare the efficacy of transcutaneous immunotherapy via laser-generated micropores to subcutaneous injection. METHODS: BALB/c mice were sensitized by intraperitoneal injection of recombinant grass pollen allergen Phl p 5 together with alum. Subsequently, lung inflammation was induced by repeated intranasal challenge. During the treatment phase, adjuvant-free Phl p 5 was applied in solution to microporated skin or was subcutaneously injected. Lung function and cellular infiltration; Phl p 5-specific serum levels of IgG1, IgG2a, and IgE; and cytokine levels in bronchoalveolar lavage fluids as well as in supernatants of splenocyte cultures were assessed. RESULTS: Both therapeutic approaches reduced airway hyperresponsiveness and leukocyte infiltration into the lungs. Whereas subcutaneous immunotherapy induced a systemic increase in Th2-associated cytokine secretion, transcutaneous application revealed a general downregulation of Th1/Th2/Th17 responses. Successful therapy was associated with induction of IgG2a and an increase in FOXP3+ CD4+ T cells. CONCLUSIONS: Transcutaneous immunotherapy via laser microporation is equally efficient compared with conventional subcutaneous treatment but avoids therapy-associated boosting of systemic Th2 immunity. Immunotherapy via laser-microporated skin combines a painless application route with the high efficacy known from subcutaneous injections and therefore represents a promising alternative to established forms of immunotherapy.

Enabling clinicians, researchers, and educators to build custom web-based biomedical information systems.

We describe an open-source toolkit that enables clinicians, researchers, and educators to build their own web-based biomedical information systems. The Web Interfacing Repository Manager (Wirm) is a high-level application server aimed at medical professionals, allowing them to create individually tailored systems for managing their multimedia data and knowledge. We provide an overview of the features of Wirm, explaining how they meet the requirements for supporting biomedical information management, and describe four applications that are currently being developed with Wirm: MyPACS, a teaching file authoring system for radiologists, Fathom, an experiment management system for natural language processing, the Digital Anatomist Repository, an image archiving tool for medical schools, and Ontolog, a browser for medical vocabularies.

Normal myelination of the pediatric brain imaged with fluid-attenuated inversion-recovery (FLAIR) MR imaging.

BACKGROUND AND PURPOSE: As in adult imaging, FLAIR can be applied to pediatric brain imaging, and this requires an appreciation of the normal pediatric brain appearance by FLAIR imaging. The purpose of this study was to describe the MR appearance of the brain in normal infants and young children as demonstrated by fluid-attenuated inversion-recovery (FLAIR) MR imaging. METHODS: We retrospectively examined MR brain studies, interpreted as normal by pediatric radiologists, from 29 patients (aged 1 to 42 months) to catalog the appearance of myelination in multiple brain areas. RESULTS: On T2-weighted images, white matter progressed from hyperintense to hypointense relative to adjacent gray matter over the first 2 years of life. An analogous, although slightly delayed sequence was observed on FLAIR images with the exception of the deep cerebral hemispheric white matter, which followed a triphasic sequence of development. On FLAIR images, the deep cerebral white matter was heterogeneously hypointense relative to gray matter in the young infant, became hyperintense early in the first few months of life, and then reverted to hypointense during the second year of life. CONCLUSION: The normal appearance and development of brain white matter must be taken into account when interpreting FLAIR images of infants and young children.

Brachydactyly type A1 with abnormal menisci and scoliosis in three generations.

We report a three-generation family in which four members had brachydactyly type A1, degenerative arthritis of the knee as a complication of abnormal menisci, and variable scoliosis. Nine of the 15 individuals in the two generations preceding the proband had brachydactyly. Three of these nine had degenerative arthritis of the knee including the proband's father who had meniscal degeneration with tears. One other had radiologically confirmed discoid menisci. Of those with brachydactyly, five also had scoliosis. Although autosomal dominant inheritance of brachydactyly A1 and discoid menisci have been reported separately, cosegregation of these features in one family has not previously been described and seems to comprise a unique autosomal dominant condition. The combination of brachydactyly, meniscal abnormalities including discoid meniscus, and scoliosis suggests that this disorder represents a new osteochondrodysplasia syndrome.

Anatomy of the spinal cord in patients with meningomyelocele with and without hypoplasia or hydromyelia.

We compared the cross-sectional areas of spinal cords of patients with normal cords to the area of patients with meningomyelocele. The control group consisted of examinations of 27 patients with normal spinal cords providing 1547 axial images at 20 levels, C2-L2. The meningomyelocele group consisted of 67 MRI examinations of 41 patients, providing 4,095 axial images at 23 levels C2 to S1. Thirty-four examinations were of 21 patients with minimal hydromyelia, 7 examinations were of 3 patients with operable hydromyelia, and 26 examinations were of 17 patients without hydromyelia. In an additional analysis, we selected those meningomyelocele patients with cord tethering but without hydromyelia or hypoplasia (53 examinations of 30 patients) and compared them to symptomatic hypoplasia cases (9 examinations of 6 patients). The symptomatic hypoplasia cases were chosen because of progressive loss of muscle strength and worsening spasticity not relieved by surgical adhesiolysis. The test, retest error was 5.6% with differences between the means of repeated readings not being significant. All tests for significance were paired T test. The areas of spine levels C7-L2 for the controls were significantly larger than for the meningomyelocele patients (p = 0.000007). Including all levels C2-S1, the minimal hydromyelia cases were not significantly different from those without hydromyelia (p = 0.5). The areas C2-S1 of operable hydromyelia cases were larger than both non-shunted minimal hydromyelia (p = 0.00009) and of meningomyelocele patients without hydromyelia (p = 0.00003). The areas C7-L2, of hypoplasia cases were significantly smaller compared to the "normal" meningomyelocele cases (p = 0.0004). These data suggest that hydromyelia stimulates overgrowth of the cord, as does hydrocephalus of the brain, and that adhesiolysis procedures are of no value with hypoplasia of the spinal cord.

Quantitative comparison of conventional spin echo and fast spin echo during brain myelination.

PURPOSE: Fast SE (FSE) sequences have largely replaced conventional SE (CSE) T2-weighted sequences in the brain and have been generally accepted as qualitatively comparable. The purpose of the present study was to subject these sequences to a quantitative comparative analysis in the brain. METHOD: A quantitative analysis of relative signal intensities of white and gray matter was performed comparing CSE and FSE T2-weighted sequences in brains of 20 children at varying stages of myelination. RESULTS AND CONCLUSION: At all ages in individual patients, white matter had less signal intensity (SI) relative to gray matter on FSE than CSE, though the relative difference in SI was small. This resulted in white matter appearing slightly more myelinated on FSE than CSE. This difference is attributed to differences in magnetization transfer. In myelinated brain (white matter hypointense to gray matter), contrast-to-noise was greater with FSE, while in unmyelinated brain, contrast-to-noise was greater with CSE.

Humoral hypercalcemia due to an occult renal adenoma.

Humoral hypercalcemia refers to the elevated blood calcium levels caused by neoplasms which release a bone resorptive substance into the circulation. Previously reported infants with malignant and benign solid tumors causing humoral hypercalcemia have presented with large abdominal masses. The case we describe, a hypercalcemic infant due to an occult parathyroid hormone-related protein-containing metanephric adenoma of the kidney, shows that radionuclide bone scanning can be a useful test to identify humoral hypercalcemia. Humoral hypercalcemia stemming from a soft tissue neoplasm should be ruled out, even in the absence of clinical signs of a tumor, if bone scans show generalized uptake in the absence of hypervitaminosis D or radiological signs of bone lesions, and serum parathyroid hormone is low.

Cervical spine MRI in abused infants.

OBJECTIVE: To determine clinical utility of screening with cervical spine MRI to detect unsuspected cord injury in children with head injury from child abuse. DESIGN: Prospectively collected case series. Setting-Tertiary care children's hospital and county medical examiner's office. PATIENTS: Twelve children with intracranial injury secondary to child abuse. None was clinically suspected to have cord injury. Includes all eligible children whose attending felt: (a) needed follow-up cranial imaging: (b) could be safely imaged; and (c) whose caretakers consented between November, 1991 and September, 1994. INTERVENTIONS: MRI scans of the cervical spine were obtained either more than 3 days after clinical presentation or postmortem. MAIN OUTCOME MEASURES: Clinical observations by neurologist, child protection team pediatrician and medicinal examiners by prospective protocol. MRI scans evaluated by prospective radiology protocol with emphasis on cervical cord injury. RESULTS: Four of the five autopsied children had small subdural or subarachnoid hemorrhages at the level of the cervical spine; MRI scan did not identify them. MRI did not identify cord injury in any child studied. CONCLUSION: Routine cervical spine MRI scans are probably not warranted in children with head injury secondary to child abuse without clinical symptoms of cervical cord injury.

Epidemiology of tethered cord with meningomyelocele.

This paper describes the epidemiology of tethered cord syndrome and its etiologies and co-morbidities following initial repair of both meningomyeloceles and lipomeningomyelocele. A review of the pertinent literature and data from 654 cases of meningomyelocele and 118 cases of lipomeningomyelocele has been drawn from a computerized database, Patient Data Management System/fx. Only cases born since 1964 were analyzed for the etiologies, co-morbidities, spinal cord abnormalities detected by contrast studies or MRI and for significant symptoms and signs. Tethered cord symptoms were related to an attachment to a rigid tether for all 31 cases following lipomeningomyelocele repair but 62 (75%) of the 83 post meningomyelocele repair patients developed the symptoms of tethered cord. Causes other than, or in addition to, tethering included an obstructed cerebrospinal fluid shunt, syringohydromyelia, benign tumor and spinal cord hypoplasia. Quantitative differentiation between asymptomatic thin spinal cords and symptomatic spinal cord hypoplasia as well as between central canal enlargement and symptomatic syringohydromyelia could not be demonstrated. Collaborative, multi-center studies of larger numbers of patients are recommended.

Spinal subdural enhancement after suboccipital craniectomy.

PURPOSE: To characterize transient intraspinal subdural enhancement (potentially mimicking the subarachnoid spread of tumor) seen on MR images in some children after suboccipital craniectomy for posterior fossa tumor resection. METHODS: Radiologic and medical records of 10 consecutive children who had MR imaging for spinal staging after resection of posterior fossa tumor during a 9-month period were reviewed retrospectively. In addition, one case with similar findings of intraspinal enhancement on spinal staging MR images obtained at another institution was included in the review. RESULTS: Intraspinal enhancement thought to be subdural was seen in four of 10 patients undergoing spinal staging MR imaging 6 to 12 days after surgery. In these four patients, MR studies 50 to 18 days later, without intervening treatment, showed resolution of the abnormal enhancement. A fifth patient (from another institution) with similar intraspinal enhancement underwent CT myelography 4 days later, which showed no subarachnoid lesions. No metastases have developed in any of these five patients during the 2.5- to 3.5-year follow-up period. conclusions: From analysis of the MR appearance and on the basis of prior myelographic experience, we suggest an extraarachnoid, probably subdural, location of this enhancement. Awareness of this phenomenon will reduce the rate of false-positive diagnoses of metastatic disease. Preoperative spinal staging should be considered for patients undergoing suboccipital craniectomy.

Marinesco-Sjögren syndrome: clinical and magnetic resonance imaging features in three children.

The authors describe clinical and MRI features of a girl and two boys, aged 9, 17 and 19 years, respectively, with Marinesco-Sjögren syndrome. The clinical findings included the major features of the syndrome, including growth deficiency, ataxia, cataracts, hypogonadism (in two) and seizures (in two). Truncal hypotonia (in three), microcephaly (in two) and leg spasticity (in two) were also present. MRI showed a very small cerebellar vermis in all three patients, various supratentorial abnormalities, an apparently small anterior pituitary gland in two and the absence of a posterior pituitary gland in all three. The MRI features are similar to the few reported pathologic findings for persons with Marinesco-Sjögren syndrome. MRI may be helpful in the early diagnosis of the disorder.

Efficient searching for specific resources on the World-Wide Web: creation of a search server for radiologists.

OBJECTIVE: Our objective was to develop an efficient way to search for radiology information on the World-Wide Web (WWW). MATERIALS AND METHODS: With the Harvest Information Discovery and Access System and a DECstation 3000 computer, each week we gather and update WWW documents that relate to radiology. To limit the size of the gathered documents, certain data (such as image files) are omitted. To date, we have gathered from 20 main radiology sites. By accessing our server, thousands of documents can be efficiently searched for specific radiology information. RESULTS: At no charge, individuals with access to the WWW can request a search of our server for specific radiology information. We return to the requester in HyperText Markup Language a document with results of the search included as embedded pointers. Our server address, or uniform resource locator, is http://glimpse.cs.arizona.edu/radiology.html. CONCLUSION: Use of a server dedicated to radiology is an efficient way to search the internet for radiology resources, such as teaching files. We provide access to many sites with one search, and we select those sites to ensure that only relevant and timely information is gathered. We also index that information.

Intensity correction of phased-array surface coil images.

Phased-array coils distribute the high signal-to-noise ratio (SNR) performance of their small component surface coils over the larger area covered by the entire array. The inhomogeneous sensitivity profiles of the component surface coils result in images with very high signal near the phased-array and decreased signal far from the array. This paper presents a postprocessing algorithm for correcting these coil-related intensity variations. The algorithm's performance was evaluated by correcting images of volunteers acquired with several different receive-only phased-array surface coils.

Marinesco-Sjögren syndrome: clinical and magnetic resonance imaging features in three children.

The authors describe clinical and MRI features of a girl and two boys, aged 9, 17 and 19 years, respectively, with Marinesco-Sjögren syndrome. The clinical findings included the major features of the syndrome, including growth deficiency, ataxia, cataracts, hypogonadism (in two) and seizures (in two). Truncal hypotonia (in three), microcephaly (in two) and leg spasticity (in two) were also present. MRI showed a very small cerebellar vermis in all three patients, various supratentorial abnormalities, an apparently small anterior pituitary gland in two and the absence of a posterior pituitary gland in all three. The MRI features are similar to the few reported pathologic findings for persons with Marinesco-Sjögren syndrome. MRI may be helpful in the early diagnosis of the disorder.