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Biomedical subjects

W Dillon

Publications and source records attributed to W Dillon.

At least 19 recordsLinked to original sources

A compendium of gene expression in normal human tissues.

This study creates a compendium of gene expression in normal human tissues suitable as a reference for defining basic organ systems biology. Using oligonucleotide microarrays, we analyze 59 samples representing 19 distinct tissue types. Of approximately 7,000 genes analyzed, 451 genes are expressed in all tissue types and designated as housekeeping genes. These genes display significant variation in expression levels among tissues and are sufficient for discerning tissue-specific expression signatures, indicative of fundamental differences in biochemical processes. In addition, subsets of tissue-selective genes are identified that define key biological processes characterizing each organ. This compendium highlights similarities and differences among organ systems and different individuals and also provides a publicly available resource (Human Gene Expression Index, the HuGE Index, http://www.hugeindex.org) for future studies of pathophysiology.

Cluster Analysis↗

Three-dimensional magnetic resonance spectroscopic imaging of histologically confirmed brain tumors.

The goal of this study was to determine whether presurgical metabolite levels measured by 3D MR Spectroscopic Imaging (MRSI) can accurately detect viable cancer within human brain tumor masses. A total of 31 patients (33 exams, 39 pathology correlations) with brain tumors were studied prior to surgical biopsy and/or resection. The 3D MRSI was obtained with a spatial resolution of 0.2 to 1 cc throughout the majority of the mass and adjacent brain tissue using PRESS-CSI localization. Levels of choline, creatine and NAA were estimated from the locations of the resected tissue and normalized to normal appearing brain tissue. The data were correlated with subsequent histologic analysis of the biopsy tissue samples. Although there were large variations in the metabolite ratios, all regions of confirmed cancer demonstrated significant choline levels and a mean choline/NAA ratio of 5.84 + 2.58 with the lowest value being 1.3. This lowest value is greater than 4 standard deviations above the mean (0.52 +/- 0.13) found in 8 normal volunteers. The choline signal intensities in confirmed cancers were significantly elevated compared to normal appearing brain tissue with a mean ratio of 1.71 +/- 0.69. Spectra with no significant metabolite levels were observed in the non-enhancing necrotic core of the tumor masses. The results of this study indicate that 3D MRSI of brain tumors can detect abnormal metabolite levels in regions of viable cancer and grades and can differentiate cancer from necrosis and/or normal brain tissue.

Biomarkers, Tumor↗

Acute posterior fossa syndrome following lumbar drainage for treatment of suboccipital pseudomeningocele. Report of three cases.

The authors report on a series of patients who underwent lumbar drainage of cerebrospinal fluid (CSF) for treatment of posterior fossa pseudomeningoceles and who subsequently developed an acute posterior fossa syndrome. These patients were found to have similar radiological findings demonstrating acute mass effect secondary to movement of CSF from the pseudomeningocele into the cerebellar parenchyma. Discontinuation of lumbar drainage resulted in symptomatic and radiological improvement in all patients. From these cases the authors infer that not all pseudomeningoceles communicate directly with the subarachnoid space. A readily recognizable appearance on magnetic resonance imaging that is useful in diagnosing this reversible complication of treatment for posterior fossa pseudomeningocele is also illustrated.

Acute Disease↗

Spontaneous intracranial hypotension resulting in stupor caused by diencephalic compression.

A 51-year-old man had a 4-month history of progressive headache and gradual onset of somnolence. MRI suggested spontaneous intracranial hypotension (SIH) with diencephalic compression, but he did not improve after three epidural blood patches. He became alert following intrathecal saline infusion that normalized his CSF pressure. A CSF leak was noted on spinal MRI and confirmed with CT contrast myelography. Surgical ligation of a torn dural root sleeve isolating a ruptured Tarlov's cyst resulted in permanent cure.

Brain↗

Cavernous malformations: results of image-guided resection.

With increased use of magnetic resonance imaging (MRI), diagnosis of cavernous malformations (CMs) has become straightforward. Surgical excision is the treatment of choice for these lesions. These malformations, though, are often small and can be difficult to localize during surgery. In these cases, stereotactic resection with a frame-based system is recommended to aid in localization of the malformation. However, use of these frame-based systems can be time consuming for the surgeon and onerous for the patient. With the advent of frameless stereotactic systems, these problems can be circumvented. Therefore, stereotactic resection of 17 CMs was performed for 15 patients over the course of 2 years at our institution during an investigative trial of a frameless stereotactic device. Eight patients presented with seizures, five patients with hemorrhage, and two patients with progressive headaches. Twelve of fifteen patients had normal neurological examination results on presentation, whereas three patients had deficits resulting from intracranial hemorrhages. All patients underwent diagnostic MRI preoperatively. Fourteen lesions were found to be cortical and subcortical; the other three lesions were in the basal ganglia, lateral ventricle, and pons. Following resection, 11 of 15 patients improved. Two patients developed postoperative deficits shortly after resection. One patient with a preoperative neurological deficit remained unchanged, and one patient had a recurrence of a deficit several months following resection. Image-guided stereotactic resection provides for easy localization of small malformations without requiring the use of a stereotactic frame or retractor and is well suited for resection of cavernous malformations.

Adolescent↗

Neutrophils, differentiated macrophages, and monocyte/macrophage antigen presenting cells infiltrate murine epidermis after UV injury.

We asked whether, as in humans, a population of antigen-presenting macrophages infiltrates the epidermis of ultraviolet (UV)-exposed BALB/c mice. Using three-color flow cytometry on cell suspensions plus in situ immunofluorescence microscopy, the phenotype of normal Langerhans cells was class II major histocompatibility complex (MHC+), CD11b+, NLDC-145+, BM8+ CD45+ and homogeneous. By contrast, in epidermal cells harvested 3 d following UV (UV-EC), there were two subsets of class II MHC+ cells: 1) class II MHChi CD11b+, and 2) class II MHClo CD11b-. Neither expressed the Langerhans cell markers BM8 and NLDC-145. In addition, there were two major populations of class II MHC- CD11b+ cells; half of these expressed the GR-1 neutrophil marker. Langerhans and dendritic epidermal T cells were markedly reduced after UV injury. By electron microscopy, immunomagnetic bead-purified CD11b+ cells in UV-EC were comprised of neutrophils, differentiated macrophages, and mononuclear cells with prominent lysosomes, but no Birbeck granules; the class II MHC+ subset resembled a monocytic cell in between differentiated macrophages and indeterminate dendritic cells. Functionally, immediately following in vivo UV exposure, the allogeneic antigen-presenting cell capacity of UV-EC was reduced to 21 +/- 6% of control epidermal cells (C-EC); by 3 d, antigen-presenting cell activity of UV-EC had recovered to 59 +/- 11% of C-EC, although at this time NLDC-145+ Langerhans cells had reached their lowest number. The recovered antigen-presenting cell activity was critically dependent upon the class II MHChiCD11b+ cells. Sensitization of BALB/c mice through skin that contained these antigen-presenting cells (3 d after UV) resulted in tolerance to dinitrofluorobenzene. By contrast, sensitization through UV-exposed skin immediately after the exposure resulted in unresponsiveness without tolerance, demonstrating temporal association of tolerance with leukocytic infiltration. In summary, murine epidermis responds to an acute UV injury in vivo with an initial abrogation of antigen-presenting activity followed by epidermal infiltration with neutrophils, differentiated macrophages, and monocytic antigen-presenting cells that are distinct from Langerhans cells with regard to expression of Langerhans cell markers and ultrastructure.

Animals↗

Magnetic resonance imaging of brain herniation into the middle ear.

Four patients with cholesteatoma were shown to have a large area of eroded tegmen tympani on computed tomography (CT). Magnetic resonance imaging (MRI) in the coronal and sagittal plane showed temporal lobe herniation in three cases and cholesteatoma with abscess elevating the dura in one case. In the patient with a cholesteatoma and an eroded tegmen tympani on CT, MRI is indicated to rule out brain herniation into the middle ear.

Adult↗

Preservation of normal cognitive functioning in elderly subjects with extensive white-matter lesions of long duration.

Although deep white-matter brain lesions are seen on magnetic resonance imaging in about one third of elderly subjects, their clinical significance is not known. In 1984, we studied three retired teachers who had extensive deep white-matter brain lesions on magnetic resonance imaging, yet functioned cognitively at an above-average level. Blinded review of 1981 computed tomographic scans revealed patchy white-matter lucencies for two of the subjects. Repeated magnetic resonance imaging in 1987 showed that the deep white-matter brain lesions were at least as extensive as in the initial study. One subject had developed renal failure, while the other two continued to function at a high level with no evidence of cognitive decline or psychiatric or neurologic impairment. The presence of extensive deep white-matter brain lesions for up to 7 years in two subjects whose cognitive, behavioral, and neurologic functioning is unimpaired suggests that deep white-matter brain lesions do not necessarily indicate a clinically significant central nervous system disease process.

Age Factors↗

Three-dimensional gradient-recalled MR imaging as a screening tool for the diagnosis of cervical radiculopathy.

The purpose of the study was to implement and assess a fast-screening, three-dimensional Fourier transformation (3DFT) MR sequence for the cervical spine. This sequence maintains adequate signal-to-noise and image contrast similar to gradient-recalled echo two-dimensional Fourier transformation (2DFT) imaging. Thirty patients with radiculopathy were examined with 3DFT gradient-recalled echo imaging. The data set consisted of 60 contiguous 1.5- to 2.0-mm-thick axial slices with a total coverage of 9 to 12 cm. In 10 patients, comparison was made with 4-mm-thick axial T1-weighted spin-echo 2DFT or gradient-recalled echo 2DFT studies. With the use of a volume acquisition, adequate signal-to-noise and image contrast similar to T2-weighted gradient-recalled echo 2DFT acquisitions were obtainable. Coverage was improved despite the use of thinner sections without interslice gap. Thin-section 3DFT provided superior detail of acquired foraminal and spinal canal stenosis and disk morphology. Limitations included increased sensitivity to patient motion and "wraparound" artifact in the slice-select direction. Overall, diagnostic confidence was improved with 3DFT owing to the reduction of partial volume artifact. We have adopted this technique as the primary screening method for diagnosing cervical radiculopathy.

Cervical Vertebrae↗

Multicenter double-blind placebo-controlled study of gadopentetate dimeglumine as an MR contrast agent: evaluation in patients with cerebral lesions.

A multicenter double-blind randomized study was designed to evaluate and compare the safety and diagnostic efficacy of gadopentetate dimeglumine (Gd-DTPA) (0.1 mmol/kg) against a saline placebo for use as an IV contrast agent for MR. The randomization code provided for a 2:1 ratio of Gd-DTPA and saline patients. Six investigators studied 88 patients with signs and symptoms of a cerebral lesion. Although safety data were complete in all 88 cases, only 83 had valid efficacy data (57 received Gd-DTPA, 26 placebo). Three patients were excluded from efficacy evaluation because of incomplete scans or scans with severe motion artifacts. Two patients were excluded for protocol variations (did not have a mass lesion). The protocol required that spin-echo MR images be acquired both before and after infusion at mode 1, 500/30/2 (TR/TE/excitations), and at a single-echo mode 2 sequence within a selected range, 1500-2000/56-90/2. Additional TEs could also be used at the discretion of each investigator. Efficacy was determined by comparing post- with preinjection images for relative degree of enhancement and improvement of diagnostic ability after injection, and by comparing these results with placebo results. Enhancement was reported in 43 (75%) of 57 Gd-DTPA patients and in none of the 26 placebo patients. Improvement of diagnostic ability was noted in 37 of 57 Gd-DTPA patients and in no placebo patients. Of 17 patients receiving Gd-DTPA for whom no diagnosis could be made before infusion, nine of 17 were diagnosed after infusion. By comparison, none of five patients not diagnosed before infusion of placebo could be diagnosed after infusion. Of 43 patients in whom lesion enhancement was observed after Gd-DTPA infusion, the diagnosis changed after infusion in 16 (37%) and the number of lesions detected after infusion increased in 10 (23%). Safety studies showed no clinically significant abnormal trends. Minor changes in blood pressure, pulse, and serum iron levels were noted in a higher percentage of Gd-DTPA patients. This study confirms that Gd-DTPA is an efficacious contrast agent for use with MR and that it exhibits excellent patient tolerance. Enhancement allows for a decisive diagnosis to be made in selected cases in which such capability had previously been lacking with unenhanced MR.

Adolescent↗

Intraoral sensation in patients with brainstem lesions: role of the rostral spinal trigeminal nuclei in pons.

Two patients with caudal pontine lesions had diminished intraoral sensation for all modalities sparing facial sensation. A third patient with lateral medullary infarction developed diminished facial pain and temperature sensation sparing intraoral structures. This segregation of intraoral sensation within the brainstem is consistent with animal studies which show that the rostral spinal trigeminal nuclei in the caudal half of the pons play an important role in intraoral and dental sensation.

Adult↗

Unilateral normal perfusion pressure breakthrough after carotid endarterectomy: case report.

The authors report a case of unilateral malignant cerebral edema that occurred after the removal of a high grade atheromatous lesion of the ipsilateral internal carotid artery. A form of unilateral normal perfusion pressure breakthrough caused by postischemic impairment of cerebrovascular autoregulation and exacerbated by systemic hypertension is thought to have contributed to this complication. Control of the hypertension and treatment of the cerebral edema with mannitol and dexamethasone led to a complete neurological recovery.

Aged↗

Magnetic resonance imaging and characterization of normal and abnormal intracranial cerebrospinal fluid (CSF) spaces.

A retrospective review of twenty-five normal MRI brain studies performed with the spin-echo technique focused special attention on the ventricular and extraventricular cerebrospinal fluid (CSF) and revealed unique signal intensity characteristics in the two locations. In addition, MRI studies of ten patients with abnormal extraaxial fluid collections either missed with CT or indistinguishable from CSF on CT images were also analyzed. MRI is more sensitive when compared to CT in evaluating the composition of CSF. Unique signal intensity characterizes the two major CSF compartments and presumably reflects their known but subtle difference in protein concentration (10-15 mg%). Normal variant or abnormal developmental fluid collections can be better characterized with MRI than with CT. These preliminary observations are offered in view of their implications for patient management and suggest further investigation.

Brain↗

Epidural block: myelographic evaluation with a single-puncture technique using metrizamide.

A simplified technique using metrizamide for myelographic delineation of extrinsic spinal cord blocks is described. This method was successfully used in eight consecutive examinations without adverse effects. A single lumbar puncture is followed by instillation of metrizamide into the subarachnoid space. With the needle left in place and the patient in the Trendelenburg position, the contrast agent is sequentially displaced above any encountered extradural blocks by further injection of diluent or sterile saline into the caudal thecal sac. Thus, multiple levels of blockage may be defined at their upper and lower margins. This method offers an expedient and safe alternative to combined lumbar and C1-2 lateral cervical puncture, leaves a minimum amount of metrizamide "trapped" below a block, and has several advantages over use of iophendylate. Additionally, the examination may be supplemented with CT scanning when desirable.

Adult↗

A CT-clinical approach to patients with symptoms related to the V, VII, IX-XII cranial nerves and cervical sympathetics.

Forty-three patients who had signs and symptoms possibly related to the extracranial course of cranial nerves V, VII, IX, X-XII, and the cervical sympathetics were examined prospectively using high resolution CT to obtain images of thin sections during rapid drip infusion of contrast material. Anatomic areas in the scan protocols included the posterior fossa, cavernous and paranasal sinuses, skull base, temporal bone, nasopharynx, parotid gland, tongue base, and neck. Nine of the 23 patients with possible fifth nerve deficits had extracranial structural lesions that explained the symptoms; none of these nine, however, had typical trigeminal neuralgia. Of eight patients with peripheral seventh nerve abnormalities, two had positive findings on scans. No patient with classic Bell palsy had a positive finding on CT. Two of five patients presenting with the Horner syndrome had positive findings on CT. Of five patients presenting with referred ear pain, three had carcinoma of the upper aerodigestive tract. Our experience suggests that patients at high risk for structural lesions responsible for cranial nerve deficits can be selected by clinical criteria. Moreover, it is essential to extend the CT examination of such patients beyond the skull base when clinically indicated. Protocols for each clinical setting are presented.

Accessory Nerve↗

Magnetic resonance of the brain: the optimal screening technique.

Seventy consecutive patients were examined with magnetic resonance (MR) and computed tomography (CT) of the brain. Each study was independently reviewed. Focal abnormalities were detected by one or both modalities in 51 patients. Neoplastic, infectious, vascular, demyelinating, metabolic, and congenital disorders of the brain were included. The MR pulse sequence that best detected these abnormalities was a spin-echo multisection technique that used a long interval between RF excitations (TR = 1500 or 2000 msec). Forty-eight of 51 patients showed focal lesions with this technique. A supplementary MR pulse sequence with a short TR (500 msec) was useful in helping to characterize certain lesions with a long T1 relaxation component, but in 10 of 26 positive cases in which this sequence was added it would have missed the abnormality had it been the sole sequence used. MR missed focal lesions in 3 of 51 patients. These were lesions that required thin-section (1.5 mm) CT techniques. Two were intrasellar, and one was an intracanalicular neurinoma. In 17 of 48 patients, CT missed the focal lesion seen with MR. Based on this experience, it is concluded that the long TR multisection spin-echo sequence is the optimal MR screening technique for detection of most brain abnormalities, and is more sensitive than CT. Currently, CT remains the screening modality of choice when high-resolution, thin-section studies in the pituitary, inner ear, and orbital regions are indicated.

Brain Diseases↗