Prognostic significance of anaplasia and angiogenesis in childhood medulloblastoma: a pediatric oncology group study

The purpose of this study was to investigate whether quantitative assessment of cytologic anaplasia and angiogenesis may predict the clinical prognosis in medulloblastoma and stratify the patients to avoid both undertreatment and overtreatment. Medulloblastomas from 23 patients belonging to the Pediatric Oncology Group were evaluated with respect to some prognostic variables, including histologic assessment of nodularity and desmoplasia, grading of anaplasia, measurement of nuclear size, mitotic cell count, quantification of angiogenesis, including vascular surface density (VSD) and microvessel number (NVES), and immunohistochemical scoring of vascular endothelial growth factor (VEGF) expression. Univariate and multivariate analyses for prognostic indicators for survival were performed. Univariate analysis revealed that extensive nodularity was a significant favorable prognostic factor, whereas the presence of anaplasia, increased nuclear size, mitotic rate, VSD, and NVES were significant unfavorable prognostic factors. Using multivariate analysis, increased nuclear size was found to be an independent unfavorable prognostic factor for survival. Neither the presence of desmoplasia nor VEGF expression was significantly related to patient survival. Although care must be taken not to overstate the importance of the results of this single-institution preliminary report, pathologic grading of medulloblastomas with respect to grading of anaplasia and quantification of nodularity, nuclear size, and microvessel profiles may be clinically useful for the treatment of medulloblastomas. Further validation of the independent prognostic significance of nuclear size in stratifying patients is required.     

A rare complication of intrathecal methotrexate in a child with acute lymphoblastic leukemia

Methotrexate (MTX) is an essential component of chemotherapy for childhood acute lymphoblastic leukemia (ALL). Both intravenous and most commonly intrathecal routes of MTX have been implicated in acute, subacute, and chronic neurotoxicity syndromes. Subacute MTX neurotoxicity occurs within days to weeks after the intravenous or intrathecal therapy and characterized by a distinct presentation with remarkable clinical resemblance to stroke, including hemiparesis, hemisensory deficits, aphasia, dysarthria, dysphagia, and diplopia. Herein the authors describe the clinical and typical neuroimaging features of a female patient with ALL who presented with subacute MTX neurotoxicity that rapidly progressed to a severe clinical condition in a few hours but eventually resolved completely with dexamethasone and folinic acid. Subacute MTX neurotoxicity is a transient neurological dysfunction that should be considered in patients presenting with stroke-like and various neurological symptoms 10 to 14 days after intrathecal therapy and diffusion-weighted magnetic resonance imaging should be undertaken for the correct diagnosis and exclusion of possible ischemic infarct. Discontinuation of subsequent intrathecal MTX therapies should be considered in severe cases and treatment with dexamethasone and folinic acid may help to resolve the symptoms.     

Highly sensitive detection of nanoparticles with a self-referenced and self-heterodyned whispering-gallery Raman microlaser

Optical whispering-gallery-mode resonators (WGMRs) have emerged as promising platforms for label-free detection of nano-objects. The ultimate sensitivity of WGMRs is determined by the strength of the light–matter interaction quantified by quality factor/mode volume, Q/V, and the resolution is determined by Q. To date, to improve sensitivity and precision of detection either WGMRs have been doped with rare-earth ions to compensate losses and increase Q or plasmonic resonances have been exploited for their superior field confinement and lower V. Here, we demonstrate, for the first time to our knowledge, enhanced detection of single-nanoparticle-induced mode splitting in a silica WGMR via Raman gain-assisted loss compensation and WGM Raman microlaser. In particular, the use of the Raman microlaser provides a dopant-free, self-referenced, and self-heterodyned scheme with a detection limit ultimately determined by the thermorefractive noise. Notably, we detected and counted individual nanoparticles with polarizabilities down to 3.82 × 10⁻⁶ μm³ by monitoring a heterodyne beatnote signal. This level of sensitivity is achieved without exploiting plasmonic effects, external references, or active stabilization and frequency locking. Single nanoparticles are detected one at a time; however, their characterization by size or polarizability requires ensemble measurements and statistical averaging. This dopant-free scheme retains the inherited biocompatibility of silica and could find widespread use for sensing in biological media. The Raman laser and operation band of the sensor can be tailored for the specific sensing environment and the properties of the targeted materials by changing the pump laser wavelength. This scheme also opens the possibility of using intrinsic Raman or parametric gain for loss compensation in other systems where dissipation hinders progress and limits applications.There is an increasing demand for new technologies to detect small molecules, nanoparticles, and airborne species (1–4). In the past decade we have witnessed a boost in the number of label-free detection techniques with varying levels of sensitivities. Techniques relying on electrical conductance (5), light scattering and interferometry (6–8), surface and localized plasmon resonance (9, 10), nanomechanical resonators (11, 12), and optical resonances (13–17) have been demonstrated.Whispering-gallery-mode (WGM) microresonators with their high quality factor, Q, and small mode volume, V, are known to enhance light–matter interactions and have extraordinary sensitivities to changes and perturbations in their structure or proximity (18, 19). They have been of great interest for sensing biomarkers, DNA, and medium-size proteins at low concentrations, as well as for detecting viruses and nanoparticles at single-particle resolution (19–31). A particle or molecule entering the mode volume of a resonator or binding onto its surface induces a net change in the polarizability of the resonator-surrounding system and perturbs its optical properties (19). This manifests itself as a shift of the resonance frequency, broadening of the resonance linewidth, or formation of a doublet via mode splitting depending on the interaction strength and the scattering and absorption properties of the binding particle or the molecule (14, 15, 17, 32, 33).In WGM sensors, the fundamental limit of sensitivity is determined by Q/V, which quantifies the strength of the interaction between the particle and the cavity field. Thus, it can be improved by decreasing V or increasing Q. One can increase Q by compensating the losses and decrease V by shrinking the size of the WGM resonator (WGMR). However, decreasing the resonator size below a critical value inevitably increases bending losses and eventually decreases Q. Instead, hybrid systems combining high-Q WGMs with highly confined (small-V) localized plasmons have been demonstrated (21, 22, 24, 27, 34), achieving detection of single proteins and very small viruses. Q enhancement of WGM resonances by compensating losses via optical gain has also been demonstrated (15, 35, 36) in silica microtoroids doped with rare-earth ions such as erbium (Er³⁺) and ytterbium (Yb³⁺). Resonators with optical gain are referred to as active resonators (36–38). When such a WGMR is optically pumped above lasing threshold, the resultant laser has a narrower linewidth than the cold cavity and thereby improves the detection limit and sensitivity beyond what can be achieved by the passive (no optical gain-providing mechanism) or by the active resonator below lasing threshold (15, 35, 38). However, fabricating WGM–plasmon hybrids and active WGMRs with dopants introduces additional processing steps and costs. For example, WGM–plasmon hybrids require preparation and adsorption of plasmonic nanostructures onto the resonator surface, and active resonators suffer from the fact that most rare-earth ions are not biocompatible and that for each different wavelength band of operation a different rare-earth ion and a different pump laser should be used.     

Transient neonatal hypoglycemia: cranial US and MRI findings

A case of transient neonatal hypoglycemia with patchy hyperechogenic white matter abnormalities in the frontal and parietooccipital lobes on cranial US is presented. An MRI examination revealed T1 and T2 shortening of the lesions in the occipital and frontal white matter. Follow-up cranial US demonstrated recovery of white matter changes in the patient with normal neurological outcome.     

Virtual endoscope-assisted intracranial aneurysm surgery: evaluation of fifty-eight surgical cases.

OBJECTIVE: Better visualization of the intracranial aneurysm may improve surgical outcomes. To this aim, we evaluated the effectiveness of using virtual endoscopy (VE) during intracranial aneurysm surgery. METHODS: Fifty-eight patients with 63 intracranial aneurysms were enrolled in this study. Every patient was examined by digital subtraction angiography (DSA) and a randomly selected twenty-six cases were also examined by computed tomography (CT). CT angiography data were linked via imaging software for reconstruction of VE images. All patients were operated on using standard microsurgical procedures. Among these cases, randomly selected cohorts of twenty-six patients with 28 intracranial aneurysms were operated on also using VE-assisted surgical procedures. The surgical results of both groups were compared to determine the efficacy of the VE-assisted surgical procedure. RESULTS: Aneurysm locations, surgical timing and Hunt-Hess grade distribution were not statistically significant between both groups (p=0.948). However, significantly reduced complication rates and increased post-operative Glasgow outcome scores were observed in the VE group (p<0.05) compared to control. CONCLUSION: Aneurysms and surrounding anatomic structures were well depicted by VE in three dimensions with interactive fly-through views. This method improved our surgical results by improving visualization of the aneurysm and increasing surgical orientation. We report that this method can be very helpful to surgeons during intracranial aneurysm surgery and may reduce post-surgical complications.     

Diagnostic value of MR arthrography in detection of intrinsic carpal ligament lesions: use of cine-MR arthrography as a new approach

Twenty-five patients with chronic wrist pain and a preliminary diagnosis of carpal instability were examined with conventional MR imaging and MR arthrography with single compartment intra-articular injection. A new cine-MR arthrography technique, with image acquisition at every 5 s during intra-articular injection, was performed in 17 subjects. The purpose of this study was to determine the diagnostic value of MR arthrography in ligamentous lesions of the wrist and to assess the value of cine-MR arthrography in comparison with arthroscopy and/or surgery. Magnetic resonance arthrography, a semi-invasive technique, increased the diagnostic accuracy of intrinsic carpal ligament injuries. Cine-MR arthrography can be considered as a promising technique especially for the evaluation of lunatotriquetral and scapholunate ligament injuries of the wrist. Received 6 December 1995; Revision received 29 November 1996; Accepted 24 February 1997     

Isolated Hemihyperplasia in an Infant: An Overlooked Sign for Wilms Tumor Development

Background

Children with overgrowth syndromes including isolated hemihyperplasia have an increased risk for developing embryonal tumors, particularly Wilms’ tumor and hepatoblastoma. Screening with sonography has been suggested as a method of identifying these tumors while they are still at an early stage.

Case Presentation

We describe an infant diagnosed with Wilms tumor in whom isolated hemihyperplasia had been overlooked by several physicians prior to the tumor diagnosis.

Conclusion

We recommend tumor surveillance for all patients with Beckwith-Wiedemann syndrome and isolated hemihyperplasia at least for the first six years of life since full molecular characterization of every patient is not readily available.     

Spinal epidural gas after cardiac surgery

The authors describe a patient with severe lower back and left leg pain in the early postoperative period after cardiac surgery. Radiologic examination revealed gas in the spinal epidural space at the level of L4-5. The pain could not be relieved with analgesics and the patient underwent lumber surgery after cardiac surgery. After decompression, the patient improved and was discharged with no symptoms.     

Diagnostic value of diffusion-weighted magnetic resonance imaging in pediatric cerebral diseases

The purpose of this study was to detect the diagnostic value of diffusion-weighted magnetic resonance imaging in different pediatric cerebral diseases involving the cerebral white and gray matter and to compare the diffusion properties with age-matched normal children. Conventional and diffusion-weighted magnetic resonance imaging were performed in 21 children with various neurologic disorders and 25 normal control subjects. Apparent diffusion coefficients were measured from the brain lesions and 12 normal-appearing white and gray matter areas in the study group. Twelve normal-appearing areas were also measured in the control group. Apparent diffusion coefficient values obtained from the normal subjects were similar to values described in the literature but were significantly different from the control subjects. Apparent diffusion coefficient values for the neurodegenerative disease group (n = 8), the anoxic encephalopathy group (n = 4), the subacute sclerosing panencephalitis group (n = 4), the acute disseminated encephalomyelitis group (n = 3), and the encephalitis group (n = 2) were respectively between 0.29-1.85 x 10(-5) cm2/s, 0.13-1.87 x 10(-5) cm2/s, 0.96-1.57 x 10(-5) cm2/s, 0.49-0.73 x 10(-5) cm2/s, and 0.42-1.50 x 10(-5) cm2/s. Although this study is limited because of the size of the patient sample and disease heterogeneity, diffusion-weighted magnetic resonance imaging provides useful and complementary information regarding the degree of involvement in different pediatric neurologic disorders.