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Biomedical subjects

A Hays

Publications and source records attributed to A Hays.

At least 19 recordsLinked to original sources

Dynamic allocation of attention in aging and Alzheimer disease: uncoupling of the eye and mind.

CONTEXT: Visual attention can be distributed focally, in the direction of gaze, or globally, throughout the extrapersonal space. Aging, and especially Alzheimer disease (AD), may influence global attention, resulting in shifts of gaze to attend to the global workspace. OBJECTIVE: To determine if subjects who have AD and cognitively intact older subjects shift their gaze more often than young subjects while viewing a dynamic stimulus that emphasizes global attention. DESIGN: Experimental study of eye fixation patterns in response to a simulated driving scene with stationary and moving distractors. SETTING: Urban, medical school, National Institute on Aging-funded Alzheimer's Disease Center. PARTICIPANTS: Thirteen subjects with mild probable AD, 13 age-comparable cognitively intact older control subjects, and 11 young control subjects. MAIN OUTCOME MEASURE: Proportion of eye fixations within and outside of a central region of interest encompassing the "road" surface. RESULTS: Young controls made significantly more eye fixations (mean number of eye fixations, 47.5) than either of the other 2 groups (older controls mean, 33.2; patients with AD mean, 32.2). However, 76% of their fixations remained within the central region of interest. Older controls and subjects with AD made proportionately fewer fixations within this region (48% and 49%, respectively) than young controls and moved their eyes more often to the periphery but did not differ from one another. CONCLUSIONS: Young controls maintain central eye position regardless of peripheral distraction. Older controls move their eyes to the periphery, presumably to widen the window of attention. Subjects with mild AD did not experience an additional disadvantage beyond that associated with aging.

Adult↗

Dopamine agonists reorient visual exploration away from the neglected hemispace.

OBJECTIVE: To study the effects of bromocriptine, a dopamine agonist, on visual search. BACKGROUND: The anatomic substrate of spatial attention takes the form of a distributed network with interconnected cortical (frontal, parietal, and cingulate) and subcortical (striatal and thalamic) components. Dopamine appears to exert a modulatory effect on the function of this network. METHODS: Seven consecutive right-handed subjects with right-sided cerebral lesions were studied using a computerized target search paradigm. Eye movements were recorded. RESULTS: Bromocriptine caused the subjects to spend more time exploring the ipsilesional hemispace and therefore increased the relative neglect of the contralesional left hemispace. However, target detection accuracy did not change. Bromocriptine thus had a differential impact on the exploratory-motor versus sensory-perceptual components of directed attention. CONCLUSIONS: Our results show that bromocriptine may worsen some aspects of hemispatial neglect in patients with lesions that include the postsynaptic components of ascending dopaminergic pathways.

Adult↗

Subcutaneous administration of CAMPATH-1H: clinical and biological outcomes.

OBJECTIVE: A 24 week study of subcutaneous (sq) dosing with titration of CAMPATH-1H (C1H) dose against the circulating CD4+ T cell count in patients with rheumatoid arthritis (RA) was undertaken to examine the safety, biologic activity, and clinical efficacy of this approach. METHODS: All patients met American Rheumatism Association (ARA) criteria for active RA. Patients received either 0.5 or 1.0 mg of C1H subcutaneously twice per week; dosing could be doubled after the first 8 weeks of treatment and subsequently following 4 week dose intervals for lack of clinical efficacy, but was discontinued any time the CD4+ T cell count fell below 400/mm3. Patients were evaluated weekly for 2 weeks and then biweekly for clinical and laboratory variables of safety, biological activity, and disease activity. RESULTS: Ten patients were treated, 6 in the 0.5 mg cohort and 4 in the 1.0 mg cohort. Four of ten patients had a 20% modified Paulus response (2 in each cohort) while taking drug; there were minimal side effects, primarily limited to local reaction at the injection site. All patients had a > 50% drop in circulating CD4+ T cells within the first 2 weeks of therapy, with no further significant reduction; only 1/6 patients in the 0.5 mg cohort had dose limiting CD4+ T cell depression vs 2/4 in the 1.0 mg cohort. All patients developed antibodies to C1H. Appearance of anti-C1H was temporarily associated with a halt in further reduction of CD4+ T cell count despite continued C1H administration. CONCLUSION: Subcutaneous administration of C1H in low doses (0.5 mg biweekly) was well tolerated and did not result in dose limiting CD4+ T cell depletion in 5 of 6 patients. Clinical efficacy was observed in some patients but could not be maintained, possibly due to the production of anti-C1H antibodies.

Alemtuzumab↗

Polymorphisms in the human apolipoprotein-J/clusterin gene: ethnic variation and distribution in Alzheimer's disease.

Apolipoprotein-J/clusterin (APOJ/CLI) shares many biological properties with apolipoprotein-E (APOE) including, but not limited to, avid binding with beta-amyloid peptide. Thus, APOJ/CLI warrants scrutiny as a candidate Alzheimer's disease (AD) susceptibility gene. We identified seven nucleotide sequence polymorphisms in APOJ/ CLI, two of which, in exon 7, after the predicted amino acid sequence. The JVIIB variant is an asparagine-to-histidine substitution, which deletes a glycosylation signal at amino acid 317; the JVIIC variant is an aspartate-to-asparagine substitution, which forms a new glycosylation signal at position 328. Both of these coding variants, as well as two neutral polymorphisms in exon 2, were more frequent in African-Americans than Hispanics and were rare in Caucasians. However, no individual coding or noncoding variant was consistently associated with AD. At the population level, APOJ/CLI polymorphisms are frequent among persons of African descent, but probably do not alter susceptibility to AD.

Black or African American↗

Identification of Gal(beta 1-3)GalNAc bearing glycoproteins at the nodes of Ranvier in peripheral nerve.

A subset of human anti-GM1 ganglioside antibodies cross-reacts with Gal(beta 1-3)GalNAc bearing glycoproteins in peripheral nerve and spinal cord. The same oligosaccharide determinant is recognized by the lectin peanut agglutinin (PNA) which binds at the nodes of Ranvier in intact peripheral nerve. The Gal(beta 1-3)GalNAc bearing glycoproteins were isolated using PNA lectin affinity chromatography followed by separation on Western blot, and the proteins were subjected to partial amino acid sequence analysis. Two major PNA binding glycoproteins were identified in peripheral nerve and spinal cord; one had an approximate molecular weight of 120 kD and had sequence homology to the oligodendrocyte-myelin glycoprotein (OMgp). The other migrated between 70 and 80 kD and had sequence homology to the hyaluronate binding domain of versican, which has been reported to share sequence homology with the 70 kD proteins hyaluronectin and the glial hyaluronic acid binding protein (GHAP). By immunocytochemistry, OMgp was localized to the paranodal region of myelin, and the protein homologous to the hyaluronate binding domain of versican was localized to the nodal gap in peripheral nerve. These PNA binding glycoproteins might be target antigens for autoantibodies in peripheral nerve.

Amino Acid Sequence↗

Preventing postoperative acute bleeding of the upper part of the gastrointestinal tract.

Two hundred and ninety-eight critically ill patients at risk for the development of postoperative stress ulcers and bleeding were randomized into three groups. The first group comprised 85 patients who received meciadanol, a new bioflavonoid, 500 milligrams every six hours through a nasograstric tube; the second group comprised 100 patients who received sucralfate (crushed tablets), 1,000 milligrams every six hours through a nasogastric tube, and the third group comprised 113 patients who received an antacid (Maalox [magnesium aluminum hydroxide gel]) through a nasogastric tube at an initial dose of 15 milliliters every hour. The gastric pH was measured hourly and titrated to a pH greater than or equal to 4.0 in patients in the group receiving the antacid. The gastric pH was measured every two hours in the other two groups. Bleeding in the upper part of the gastrointestinal tract was determined visually (frank blood in gastric contents) or by guaiac testing. Bleeding occurred in seven patients receiving meciadanol, nine receiving sucralfate and six receiving the antacid. The difference in rates of bleeding was not statistically significant. Correlation between the severity of illness index and the development of bleeding was poor, at least in the low and intermediate index range. In contrast, there was a strong correlation between the age of the patient and the development of bleeding. Only one patient younger than 50 years had bleeding develop. Apparently, meciadanol exerts its action by a mechanism other than pH control. It may, therefore, fill an important gap in the ability to prevent postoperative stress ulcers and bleeding.

Acute Disease↗

Rupture of intracranial aneurysm during computerized tomography.

A computerized tomographic (CT) scan was performed on a patient with a suspected paraseller mass. Coincident with contrast injection, an unusual and distinctive "starburst" pattern appeared in the right parasellar region and was associated with sudden deterioration in the patient's condition. Subsequent CT and necropsy confirmed a ruptured aneurysm at the suspected site with a large subarachnoid hemorrhage. To our knowledge, this unusual CT picture of a rupturing intracranial aneurysm has not been previously illustrated.

Aged↗

Emery-Dreifuss muscular dystrophy.

A man had weakness of humeroperoneal distribution associated with limited range of motion of the cervical spine and elbows. At age 25 he developed permanent atrial paralysis, and a cardiac pacemaker was inserted. Although this case was sporadic, most others have been transmitted as an X-linked recessive trait. Mixed patterns in electromyography and muscle histology have caused nosological confusion, but the unique clinical signs seem to define a distinct form of muscular dystrophy, warranting the designation "emery-Dreifuss" type.

Adult↗

Debrancher deficiency: neuromuscular disorder in 5 adults.

Five patients, 4 men and 1 woman, had adult-onset and slowly progressive weakness. There was distal wasting in 2, hepatomegaly in 3, and congestive heart failure in 2. Electromyography showed a mixed pattern with abundant fibrillations. Serum creatine phosphokinase was increased 5- to 45-fold. Blood glucose failed to respond to epinephrine or glucagon, and venous lactate did not rise after ischemic exercise. Muscle biopsy showed vacuolar myopathy affecting both fiber types. By electron microscopy the vacuoles corresponded to large pools of glycogen not limited by a membrane. Glycogen concentration was 3 to 5 times normal in muscle and 7 to 21 times normal in erythrocytes. In the presence of iodine, muscle glycogen showed a spectrum characteristic of phosphorylase-limit-dextrin. Debrancher activity was measured by a spectrophotometric assay and by a radioactive reverse reaction. The activity was lacking in muscle and erythrocytes of 4 patients according to both assays; in 1 patient the reverse reaction was not impaired. Though previously reported in only 5 patients, debrancher deficiency myopathy may not be rare and should be considered in the differential diagnosis of adult-onset hereditary myopathies.

Adolescent↗