Reversible cerebral atrophy in recently abstinent chronic alcoholics measured by computed tomography scans.

Eight chronic alcoholics received repeated computed tomography scans. Four, who maintained abstinence and functionally improved, showed partially reversible cerebral atrophy. Two nonabstinent patients and two abstinent patients who had completed functional improvement before the first scan showed no change in atrophy.

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.

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.

Cerebral atrophy and functional deficits in alcoholics without clinically apparent liver disease.

Ninety-seven chronic alcoholics, both impaired and unimpaired, without clinically evident liver disease, showed significantly more cerebral atrophy on computed tomography than age-matched neurologic controls. Age was the variable most highly correlated with cerebral atrophy measurements, and it accounted for most of the correlations between atrophy and functional impairment, except in the Wernicke-amnesic group. Analysis of the slopes of atrophy scores versus age showed a more rapid "rate" of development of cerebral atrophy in alcoholics compared with controls. There were no correlations between liver biopsy scores (51 cases), drinking history (47 cases), or dietary intake (39 cases) and cerebral atrophy measurements.

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.

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.

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.

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.

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.

Computerized tomography (CT) in otolaryngology.

Computerized tomography (CT) of the brain has been available since 1973 and has changed neurological, neurosurgical and radiological practice beyond recognition. A rapid growth of literature has documented it role in the diagnosis of intracranial hematoma, cerebral atrophy, brain tumor, orbital lesions and postoperative tumor evaluation. This computerized method of image reconstruction is now also being applied to the rest of the body and to other diagnostic modalities such as isotopes and ultrasound. The initial impact of CT scanning in otolaryngology is largely in four areas: 1. Facial deformities either acquired or congenital as hypertelorism, fibrous dysplasia, ossifying fibroma and Crouzon's disease. 2. Tumors involving sinuses primarily or by secondary invasion. 3. Cerebello-pontine angle lesions as meningiomas, acoustic neuromas, and glomus jugulare tumors. The larger acoustic neuroma is well visualized by this technique rendering contrast myelography unnecessary. In CT scanning, subtle differences in position and an increase in density before contrast enhancement should allow a differentiation of angle meningiomas from acoustic neuromas; in addition, CT scanning has a very important role in the postoperative assessment of angle tumors. 4. Infections as cerebral abscess or cerebritis secondary to sinus or mastoid disease. The future holds changes that will allow much finer detail, re-orientation of the horizontal information into any plane, and much more accurate differentiation of tissue density. The principle of CT image reconstruction is being applied to both isotope and ultrasound scanning and should improve their accuracy and yield. If the rapid growth of the new technology over the past two years continues, even greater usefulness can be anticipated.

Clinically-directed CT in occult disease of the skull base involving foramen ovale.

Occult disease of the skull base may present as an isolated neurogenic symptom in the absence of physical signs or radiologic findings. It therefore often remains undiagnosed until advanced. Computed tomography (CT) provides the potential for diagnostic imaging far beyond conventional radiology. Not only do current generation scanners provide exquisite bone detail, they also provide the capability of soft tissue imaging. In the past year, we have matched the diagnostic problem of occult disease of the middle fossa skull base and its foramina with the potential diagnostic imaging solution of CT. Five patients were referred with possible occult middle fossa skull base disease--all had persistent unilateral facial paraesthesia in the distribution of one of the lower two trigeminal nerve divisions (V2 V3) as their only complaint; all had previously been extensively investigated (including axial CT); all remained undiagnosed. Utilizing clinically-directed CT (based on acoustic neuroma diagnostic index of suspicion and imaging experience), 2 of the 5 patients were found to have small mass lesions involving foramen ovale. This presentation will demonstrate our experience based on image-manipulated CT, actively monitored by both radiologist and otolaryngologist.

Sophisticated CT in complex maxillofacial trauma.

Conventional radiology and selective complex-motion tomography suffice for the diagnosis of isolated facial fractures. Complex facial fractures, however, require a more directed diagnostic approach, utilizing the imaging potential of computed tomography (CT). In the acutely injured but stable patient, unenhanced axial CT (preview-monitored under clinical orientation) provides the most effective, safe, reasonably rapid diagnostic examination. Direct coronal CT can also be utilized. The brain is studied by contiguous 10 mm slices; the facial skeleton is studied with contiguous 5 mm slices, which permits coronal and sagittal reformations. In suspected cervical spine injury (where direct coronal CT is contraindicated), the axial CT format above will provide essential diagnostic information and allow image reconstruction. The late complications of brain abscess and CSF leak are well imaged by CT; the latter is best assessed (during activity) by preview-controlled CT after intrathecal injection of metrizamide.

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.

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.

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).

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.