Blocking FcRn in humans reduces circulating IgG levels and inhibits IgG immune complex-mediated immune responses.

The neonatal crystallizable fragment receptor (FcRn) functions as an intracellular protection receptor for immunoglobulin G (IgG). Recently, several clinical studies have reported the lowering of circulating monomeric IgG levels through FcRn blockade for the potential treatment of autoimmune diseases. Many autoimmune diseases, however, are derived from the effects of IgG immune complexes (ICs). We generated, characterized, and assessed the effects of SYNT001, a FcRn-blocking monoclonal antibody, in mice, nonhuman primates (NHPs), and humans. SYNT001 decreased all IgG subtypes and IgG ICs in the circulation of humans, as we show in a first-in-human phase 1, single ascending dose study. In addition, IgG IC induction of inflammatory pathways was dependent on FcRn and inhibited by SYNT001. These studies expand the role of FcRn in humans by showing that it controls not only IgG protection from catabolism but also inflammatory pathways associated with IgG ICs involved in a variety of autoimmune diseases.

Gas chromatography-mass spectrometry confirmation of Cozart RapiScan saliva methadone and opiates tests.

The object of this study was to determine the sensitivity and specificity of the Cozart RapiScan onsite saliva test for methadone and opiates versus laboratory-based enzyme immunoassay (EIA) and gas chromatography-mass spectrometry (GC-MS) confirmation. Fifty saliva specimens were obtained from 28 volunteers among persons entering a substance abuse clinic. Specimens were tested onsite using the Cozart RapiScan Saliva test and Cozart RapiScan Reader. Specimens were retested by Cozart Microplate EIA assays on receipt at the laboratory and then frozen for later confirmation by GC-MS. For GC-MS, deuterated internal standards were added to specimen aliquots which were extracted using solid-phase columns at pH 6 and eluted with dichloromethane/isopropanol/ammonia (80:19:2). The dry residues were derivatized with PFOH and PFPA and dried, and the reconstituted extract was injected and quantitated by GC-MS. The Cozart RapiScan Methadone Saliva Assay was found to have a sensitivity and specificity of 100% +/- 12% versus GC-MS (2-ng/mL cutoff) and a sensitivity of 100% +/- 11% and a specificity of 95% +/- 2.4% versus the Microplate EIA for methadone (30-ng/mL cutoff). The Cozart RapiScan Saliva Opiate test had a sensitivity of 100% +/- 12% and a specificity of 92% +/- 3.2% versus GC-MS (2-ng/mL cutoff) and a sensitivity of 96% +/- 2.2% and specificity of 95% +/- 2.4% versus the Microplate EIA for opiates (30-ng/mL cutoff).

p53 binds the nuclear matrix in normal cells: binding involves the proline-rich domain of p53 and increases following genotoxic stress.

The tumour suppressor p53 is a multifunctional protein important for the maintenance of genomic integrity. It is able to form molecular complexes with different DNA targets and also with cellular proteins involved in DNA transcription and DNA repair. In mammalian cells the biochemical processing of DNA occurs on a nuclear sub-structure termed the nuclear matrix. Previously Deppert and co-workers have identified p53 in association with the nuclear matrix in viral- and non-viral transformed cell lines. In the present study we demonstrate, for the first time, that p53 is bound to the nuclear matrix in primary cultures of normal mammalian cells and that this binding increases following DNA damage. Analysis of cell lines expressing structural mutants of p53 revealed that association with the nuclear matrix is independent of the tertiary and quaternary structure of p53. However, the proline-rich domain towards the N-terminus of p53 (residues 67 to 98) appeared important for binding to the nuclear matrix. This was demonstrated by TET-ON regulated expression of p53-derived constructs in p53(-/-) murine embryonic fibroblasts (MEF p53(-/-)). The proline-rich domain of p53 has potential for SH3 protein-protein interaction, and has a role in p53-mediated apoptosis and possibly base excision repair of DNA damage. We discuss our observations in relation to the ability of p53 to facilitate DNA repair and also review evidence indicating that matrix-bound p53 in SV40-transformed cells may facilitate the transforming potential of SV40 large T antigen.

Interventional techniques in the management of disorders of the brain: current status.

The role, techniques and tools of interventional neuroradiology are growing rapidly because of the number of active investigators. Training programs are being certified by the American Society of Neuroradiology. Recommendations are that Interventional Neuroradiologists be fully qualified in neuroradiology (two years) and have a one or two-year additional fellowship in interventional. The ideal interventionalist would also have some clinical neuroscience training. While these training requirements seem excessive on the surface one must recognize that with the overall drop in routine angiography that a longer exposure is necessary to acquire the prerequisite knowledge, skill and experience easily obtained in one year ten years ago. In fact there has been some pressure to place all of diagnostic neuroangiography in the hands of interventionalists. Endovascular approaches are the treatment of choice for: (1) cerebral vasospasm, (2) carotid cavernous fistulae, (3) vertebral artery origin stenosis, (4) subclavian artery stenosis, (5) innominate and left carotid origin stenosis, and (6) giant intracranial aneurysms. Endovascular treatment is developmental and should be restricted to centers performing formal trials in the treatment of: (1) cerebral arteriovenous malformations and (2) internal carotid artery and intracranial stenosis.

Brain MRI in obsessive-compulsive disorder.

Magnetic resonance imaging (MRI) brain scans were performed on 12 patients with obsessive-compulsive disorder and 12 healthy controls. Measurements of the area of the head of the caudate nucleus, cingulate gyrus thickness, intracaudate/frontal horn ratio, and area of the corpus callosum did not differ between the two groups. These limited data do not support the presence of a consistent gross brain structural abnormality in obsessive-compulsive disorder. Further studies using other anatomic measurements and other brain structural imaging techniques are warranted.

Persistent stapedial artery supplying a glomus tympanicum tumor.

Vascular anomalies of the middle ear are extremely rare. The most common anomaly is a persistent stapedial artery. This artery is important clinically because of the risk of profuse bleeding during middle ear surgery. We describe a 26-year-old woman with a glomus tympanicum tumor. The blood supply to the tumor was from a persistent stapedial artery. A preoperative angiogram supported this finding by demonstrating a small vessel originating from the anterior branch of the middle meningeal artery as the major vascular supply to the tumor. To our knowledge, this is the first case report of a glomus tympanicum tumor vascularized by a persistent stapedial artery that was suggested by angiography and confirmed intraoperatively. To better understand this anomaly, we review the embryological development of the stapedial artery and discuss its clinical significance.

Intracranial angioplasty for treatment of vasospasm after subarachnoid hemorrhage: technique and modifications to improve branch access.

Angioplasty of the proximal portions of major cerebral arteries at the base of the brain has shown promise as a therapy for symptomatic vasospasm after subarachnoid hemorrhage. The blind-ended, single-lumen balloon-dilatation catheter most widely used to date lacks steerability, limiting its application to unbranched stems and single branches at bi- or trifurcation points. To extend the capabilities of cerebral angioplasty, we describe two modifications of the basic technique that have allowed increased selectivity and successful angioplasty of multiple branches, both proximal and distal, involved by vasospasm. Of four patients treated, three showed early improvement in their clinical condition, likely attributable to the angioplasty procedure. Our modifications to the basic angioplasty technique enhanced its success. Further refinement of this technique in the treatment of vasospasm will make it safer in treating this serious and widespread disorder.

Acute-onset Brown's syndrome associated with pansinusitis.

We treated a 5-year-old girl and a 6-year-old boy with acquired Brown's syndrome associated with pansinusitis. In both patients, the diagnosis was established roentgenographically, and the patients were treated with oral antibiotics. Systemic corticosteroids were used in one case, although their clinical value was uncertain. Patients presenting with acute-onset Brown's syndrome of undetermined cause should undergo computed imaging of the orbits and paranasal sinuses.

MR findings on primitive neuroectodermal tumors.

Primitive neuroectodermal tumors (PNETs) are highly cellular primitive CNS neoplasms that resemble microscopically the undifferentiated cells of the germinal matrix of the primitive neural tube. These tumors exhibit a highly malignant behavior with a tendency to disseminate along the CSF pathways. Previous descriptions of the neuroradiological findings in patients with PNET were published prior to the clinical application of magnetic resonance (MR) imaging. We describe our experience with the MR evaluation of four patients with pathologically proven PNET.

Penetrating intracranial wood wounds: clinical limitations of computerized tomography.

The case history of a patient with a periorbital penetrating wooden foreign body is presented. The computerized tomography (CT) densities of several different sources of wood were compared using an experimental model. The clinical usefulness and practical limitations of CT in the evaluation of intracranial foreign bodies is discussed, and the management of this type of injury is reviewed.

Rectus muscle position in V-pattern strabismus. A study with coronal computed tomography scanning.

Coronal computerized tomographic (CT) scans were obtained on ten children with previously unoperated V-pattern strabismus and ten control patients to determine the relationship of rectus muscles to the globe. All patients with V-pattern had sufficient overaction of the inferior oblique muscles to warrant bilateral surgical weakening. Control patients had no strabismus or isolated horizontal deviations without A- or V-patterns. Using a horizontal reference line constructed along the anterior cranial fossa, the mean horizontal rectus-muscle axes were found to approximate the expected value of 180 degrees closely. The vertical rectus muscle axes were excyclotorted in both groups. However, there was no significant difference in the mean superior temporal quadrant angles formed by the intersection of the horizontal and vertical rectus muscle axes. Analysis of covariance with age as the covariant demonstrated a significant relationship (P less than 0.01) between age and the superior temporal quadrant angle measured in each eye. Our data suggest that apparent rectus muscle malposition identified by CT scanning is a function of age and cannot be implicated as an important cause of V-pattern strabismus.

Midline central nervous lipomas in children.

We review the clinical, radiologic, surgical, and pathologic features of 15 children with central nervous system lipomas. Three were situated in the corpus callosum and 12 at the conus medullaris. The intracranial and the intraspinal disorders share several features suggesting that they are related. Both are midline developmental abnormalities associated with dysraphism and both may have extrinsic as well as intrinsic components. Both can occur as occult asymptomatic lesions, particularly early in life, or can be part of extensive dysraphic malformations. Computed tomography is the best way to demonstrate the nature and extent of these lesions prior to treatment.

The relationship of rectus muscles to the globe: a study with coronal CT scanning.

Coronal computerized tomographic scans of 25 patients were reviewed in order to determine the normal relationship of rectus muscles to the globe. Using a horizontal reference line constructed along the anterior cranial fossa, the mean horizontal rectus muscle axis was found to be slightly excyclotorted in both eyes, and the mean vertical rectus muscle axis slightly incyclotorted in both eyes. In addition, the mean superior temporal quadrant angle formed by the intersection of the horizontal and vertical rectus muscle axis was significantly greater than the mean superior nasal quadrant angle in the same eye. The presence of large anatomical variations in individual patients may make it difficult to implicate rectus muscle malposition as an important etiology of A- and V-pattern strabismus.

Partially reversible cerebral atrophy and functional improvement in recently abstinent alcoholics.

52 recently abstinent chronic alcoholics were given repeated psychological tests and 20 of these had repeated CT scans. The first scan was done within 5 weeks of the last drink. The degree of measurably reversible cerebral atrophy on CT scan correlated negatively with the interval between the last drink and the first CT scan. Significantly more reversibility of cerebral atrophy was noted in those subjects claiming interscan abstinence. There were positive correlations between functional improvement scores on neurological exam and reversible cerebral atrophy measurements. Significant improvement on psychological test performance was restricted to patients tested initially within 3 weeks of the last drink. Both the CT results and the psychological test results suggest that reversible changes occur soon after the cessation of drinking.

Pituitary apoplexy associated with a triple bolus test. Case report.

The authors report a case of pituitary apoplexy resulting in bilateral internal carotid artery occlusion, with marked depression of consciousness and hemiplegia. After transsphenoidal tumor decompression, restoration of flow in both carotid arteries was documented angiographically and the patient made an excellent clinical recovery. The unique aspect of this case is that the pituitary apoplexy was apparently precipitated by neuroendocrine manipulation, performed as a preoperative test of pituitary function.

Lesions simulating glomus tumors of the middle ear.

Several non-glomus middle ear masses may mimic glomus tumors. Clinical features alone may not be sufficient to differentiate these lesions. Radiography, particularly angiography is valuable in establishing the diagnosis in most cases. In some, however, diagnosis can only be made on tympanotomy. Four case reports are included in which the diagnosis turned out to be hemangioma, meningioma, high jugular bulb, and cholesterol granuloma. Careful assessment of the clinical, radiological, and operative findings is essential in order to avoid serious complications.