Effects of haloperidol on motor and cognitive functioning in aged mice

The effects of haloperidol on motor and functioning and cognitive functioning were studied in young (3-5 months old) and aged (20-22 months old) male mice by examining haloperidol-induced catalepsy and haloperidol-induced decrements in performance on a radial arm maze. The aged mice were much more sensitive to these adverse effects of haloperidol than were the young mice. Studies of the distribution of radioactivity from [3H]haloperidol to the brain indicated that the differences in sensitivity to this drug were not due to pharmacokinetic differences. The results demonstrate that mice are suitable for studies of aging-induced changes in the behavioral effects of neuroleptic agents.     

Classical and anaplastic seminoma: difference in survival

Classical and anaplastic seminoma are traditionally treated with radiation therapy and are said to have the same prognosis. A retrospective study was undertaken of 90 seminoma patients treated with radiation therapy between 1961 and 1985. The classical group consisted of 71 patients of whom 50 had stage I and 21 had stage II disease. The anaplastic group consisted of 19 patients of whom ten had stage I and nine had stage II disease. The median follow-up time was 64 months for the entire group. The 10-year relapse-free survival rate for the classical group was 94% and for the anaplastic group was 70% (P less than .05). For patients with classical stage I disease, the relapse-free actuarial survival rate was 98%; for patients with anaplastic stage I disease, it was 64% (P less than .02). For the classical stage II disease group, the relapse-free actuarial survival rate was 84% and for the anaplastic stage II disease group, 75% (P less than .70). Four patients in the classical group (6%) had relapses; of these, one patient had local recurrence of tumor, and three had distant metastases. In the anaplastic group, four patients (21%) had relapses; two patients had local recurrence of tumor, and two had distant metastases. Therefore the data suggest a difference in survival and relapse rates between classical and anaplastic seminoma.     

Characteristics of rejection of orthotopic corneal allografts in the rat

We have employed a rat model of orthotopic corneal transplantation to study the characteristics of rejection and development of systemic immunity in the host. Lewis (LEW) rats underwent a true penetrating keratoplasty using Wistar-Furth (WF) donor corneas. A rejection incidence of 55% with a mean survival time (MST) of 17.1 days was observed using these untreated allogeneic corneas. Animals undergoing rejection of these allografts developed cytotoxic T lymphocytes (CTL) capable of lysing WF lymphoblasts in a standard 51-chromium release assay. These same rats did not have delayed-type hypersensitivity (DTH) responses when compared to skin grafted controls. Rats with clear allografts had no demonstrable CTL or DTH activity. As expected, LEW rats that were preimmunized with WF skin grafts and subsequently received WF orthotopic corneal grafts rejected 100% of these corneas at an accelerated rate (MST = 9.7 days, P less than .02). We then employed a previously described technique of using latex beads to induce migration of Langerhans cells into the central cornea of the donor graft prior to transplantation. The presence of Langerhans cells in the donor cornea resulted in a higher incidence of rejection (96%) and an accelerated rate (MST = 11.8 days, P less than .02) when compared to untreated allografts. These rats also had a higher level of CTL activity and marked DTH responses. These data show that rejection of orthotopic allogeneic corneas is accompanied by the development of systemic alloimmunity as measured by CTL activity. However, these fully allogeneic corneas can be rejected in the absence of DTH responses. Langerhans cells have a dramatic effect on graft survival and are necessary for induction of DTH responsiveness in the host.     

Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis

Supravalvular aortic stenosis (SVAS) is an inherited obstructive vascular disease that affects the aorta, carotid, coronary and pulmonary arteries. Previous molecular genetic data have led to the hypothesis that SVAS results from mutations in the elastin gene, ELN. In these studies, the disease phenotype was linked to gross DNA rearrangements (35 and 85 kb deletions and a translocation) in three SVAS families. However, gross rearrangements of ELN have not been identified in most cases of autosomal dominant SVAS. To define the spectrum of ELN mutations responsible for this disorder, we refined the genomic structure of human ELN and used this information in mutational analyses. ELN point mutations co-segregate with the disease in four familial cases and are associated with SVAS in three sporadic cases. Two of the mutations are nonsense, one is a single base pair deletion and four are splice site mutations. In one sporadic case, the mutation arose de novo. These data demonstrate that point mutations of ELN cause autosomal dominant SVAS.      

Expression of HLA class I and II antigens on cells of the human trabecular meshwork

Human corneoscleral tissue containing trabecular meshwork and cultured human trabecular cells were examined for HLA-ABC (class I) and HLA-DR (class II) antigens of the major histocompatibility complex using an indirect immunofluorescence assay. Class I antigens were detected in the trabecular meshwork on frozen sections and on cultured trabecular cells. Class II antigens were constitutively expressed on some, but not all, cells within the trabecular meshwork. Many more cells could be induced to express class II antigens by pre-incubation in human gamma interferon. Cultured trabecular cells did not express class II antigens constitutively, but expression could be induced by gamma interferon. This study suggests that, in addition to Langerhans' cells at the limbus, other cell types within the anterior segment express major histocompatibility complex-encoded class II antigens either constitutively or inducibly. These cells may be important for the initiation and regulation of ocular immunity.     

A Posttraumatic Dilated,Proptotic Eye Does Not Always Need a Lateral Canthotomy! A Review of Superior Orbital Fissure Syndrome for Emergency Physicians

BackgroundSuperior orbital fissure syndrome (SOFS) is a rare constellation of findings consisting of ophthalmoplegia, ptosis, a fixed dilated pupil, forehead anesthesia, and loss of the corneal reflex. This syndrome, though rare, is most often encountered in trauma with individuals sustaining a facial fracture.Case ReportWe present a case of a young woman who was diagnosed with SOFS after a fall in her house, hitting her face on a nightstand. Treatment consisted of high-dose i.v. steroids followed by a taper with close follow-up in the Ophthalmology clinic. We provide a brief review of SOFS, including treatment considerations and follow-up.Why Should an Emergency Physician Be Aware of This?SOFS can be easily overlooked in an individual presenting to the emergency department after facial trauma with proptosis. However, a thorough examination of the eye, visual acuity, and intraocular pressure will focus the physician on SOFS rather than the need for immediate decompression via lateral canthotomy. This report describes a traumatic cause of SOFS, the pathophysiology and treatment, and summarizes existing literature.     

Corticobasal and ataxia syndromes widen the spectrum of C9ORF72 hexanucleotide expansion disease

Recently, a hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72 was reported as the cause of chromosome 9p21‐linked frontotemporal dementia‐amyotrophic lateral sclerosis (FTD‐ALS). We here report the prevalence of the expansion in a hospital‐based cohort and associated clinical features indicating a wider clinical spectrum of C9ORF72 disease than previously described. We studied 280 patients previously screened for mutations in genes involved in early onset autosomal dominant inherited dementia disorders. A repeat‐primed polymerase chain reaction amplification assay was used to identify pathogenic GGGGCC expansions. As a potential modifier, confirmed cases were further investigated for abnormal CAG expansions in ATXN2. A pathogenic GGGGCC expansion was identified in a total of 14 probands. Three of these presented with atypical clinical features and were previously diagnosed with clinical olivopontocerebellar degeneration (OPCD), atypical Parkinsonian syndrome (APS) and a corticobasal syndrome (CBS). Further, the pathogenic expansion was identified in six FTD patients, four patients with FTD‐ALS and one ALS patient. All confirmed cases had normal ATXN2 repeat sizes. Our study widens the clinical spectrum of C9ORF72related disease and confirms the hexanucleotide expansion as a prevalent cause of FTD‐ALS disorders. There was no indication of a modifying effect of the ATXN2 gene.