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Biomedical subjects

J O'Neill

Publications and source records attributed to J O'Neill.

At least 73 records · Page 4Linked to original sources

Influence of cholinesterase inhibitors on cortical slow-wave activity in aging nonhuman primate.

Substantial evidence has now accumulated suggesting that the cognitive decrements characteristic of Alzheimer's disease and, to a lesser degree, of normal aging, may result, at least in part, from degenerative changes in the cholinergic system innervating archi- and neocortices. This evidence for cholinergic degeneration in AD has provided the key rationale for many recent clinical trials utilizing cholinergic agents for the purpose of palliating cognitive loss. The basal forebrain cholinergic system plays an important function in electrocortical activation associated with behavioral arousal and cognitive functions. We recorded electrocortical changes from nonhuman primates following administration of potentially clinically useful cholinergic agonists as well as an antagonist. The cholinesterase inhibitors tacrine (THA) and, to a lesser extent, physostigmine (PHYSO) and amodiaquine (AMDQ), caused an upward shift in the frequency of the resting electrocortical activity, although scopolamine significantly slowed the activity below baseline levels. We believe these findings support the concept that the cholinergic system may play an important role in cognitive processes associated with cortical activation.

Aging↗

Isolation of a mutant Arabidopsis plant that lacks N-acetyl glucosaminyl transferase I and is unable to synthesize Golgi-modified complex N-linked glycans.

The complex asparagine-linked glycans of plant glycoproteins, characterized by the presence of beta 1-->2 xylose and alpha 1-->3 fucose residues, are derived from typical mannose9(N-acetylglucosamine)2 (Man9GlcNAc2) N-linked glycans through the activity of a series of glycosidases and glycosyl transferases in the Golgi apparatus. By screening leaf extracts with an antiserum against complex glycans, we isolated a mutant of Arabidopsis thaliana that is blocked in the conversion of high-manne to complex glycans. In callus tissues derived from the mutant plants, all glycans bind to concanavalin A. These glycans can be released by treatment with endoglycosidase H, and the majority has the same size as Man5GlcNAc1 glycans. In the presence of deoxymannojirimycin, an inhibitor of mannosidase I, the mutant cells synthesize Man9GlcNAc2 and Man8GlcNAc2 glycans, suggesting that the biochemical lesion in the mutant is not in the biosynthesis of high-mannose glycans in the endoplasmic reticulum but in their modification in the Golgi. Direct enzyme assays of cell extracts show that the mutant cells lack N-acetyl glucosaminyl transferase I, the first enzyme in the pathway of complex glycan biosynthesis. The mutant plants are able to complete their development normally under several environmental conditions, suggesting that complex glycans are not essential for normal developmental processes. By crossing the complex-glycan-deficient strain of A. thaliana with a transgenic strain that expresses the glycoprotein phytohemagglutinin, we obtained a unique strain that synthesizes phytohemagglutinin with two high-mannose glycans, instead of one high-mannose and one complex glycan.

Arabidopsis↗

Medicaid versus state funding of community residences: impact on daily life of people with mental retardation.

The unintended effects on quality of life that flow from decisions regarding funding sources used to support community-based residential programs were documented. Results show that community residence program structures play an important role in determining quality of life after deinstitutionalization. Clients living under program structures flowing from the Medicaid ICF/MR funding source were less active and involved in life than were clients living in programs funded by non-Medicaid state sources. We hypothesized that the reason for this differential outcome was the result of Medicaid funding regulations and their interpretation, which create an institutional-like set of program structures leading to restrictive care patterns.

Activities of Daily Living↗

Chronicity. Adjustment differences of Vietnam combat veterans differing in rates of psychiatric hospitalization.

The study focuses on the frequency of inpatient care for patients with Posttraumatic Stress Disorder (PTSD). This factor, termed "chronicity," is, perhaps surprisingly, largely overlooked in many PTSD studies. The significance of chronicity was addressed through administration of Minnesota Multiphasic Personality Inventory (MMPI) to Vietnam Theater and Era veterans in an inpatient psychiatry service. MMPI scores were analyzed for two main effects: combat exposure and chronicity (i.e., number of inpatient psychiatry admissions). The results replicated research showing combat exposure is associated with greater maladjustment (i.e., higher MMPI scores). Moreover, chronicity also emerged as a significantly important variable: of all groups compared, Vietnam combat veterans higher in chronicity scored higher on MMPI clinical scales, particularly on scales Paranoia, Psychasthenia, and Schizophrenia, thereby (a) empirically establishing (a) the methodological point that number of admissions must be controlled and (b) the substantive point that chronicity is important in studies of PTSD.

Adaptation, Psychological↗

Cognitive impairment, clinical course and treatment history in out-patients with bipolar affective disorder: relationship to tardive dyskinesia.

Clinical, neuropsychological and psychopharmacological characteristics were investigated for their ability to distinguish individuals with and without involuntary movements (tardive dyskinesia), among a population of 40 out-patients with bipolar affective disorder and a history of exposure to neuroleptics and lithium. Impaired performance on a test of cognitive flexibility bore the primary association with both the presence and the severity of involuntary movements. The additional relationships identified emphasized further that individual vulnerability to involuntary movements appeared to be associated not with greater duration or dosage of treatment, but with features of the bipolar illness, including number and type of affective episodes, for which that treatment was prescribed.

Adult↗

Major blunt abdominal trauma due to child abuse.

We reviewed 15 years' experience with childhood trauma at two hospitals in different cities, one a city hospital, the other a children's hospital, to learn the extent, circumstances, presentations, and consequences of major blunt abdominal trauma due to child abuse. Some 10,000 children admitted to these hospitals for treatment of injuries from 1972 through 1986 provided the basis for the study; the incidence and severity of pediatric trauma at the two hospitals was similar, in that 13% of the visits to both hospitals' emergency rooms were for trauma, of which 5% resulted in admission. Major blunt abdominal trauma due to child abuse accounted for 22 of these cases, six at the former, 16 at the latter, and represented less than 0.50% of all abused children seen at both institutions. The average age was 24 mo; 14 were boys and eight were girls. In only two instances was the family unit intact; in both, the child was abused by the babysitter. Otherwise, the father, or the mother's "boyfriend," was responsible. Overall mortality was 45%, and was related both to type of injury and presenting signs. Of one who presented with an epigastric mass due to a pancreatic hematoma, none died; the pseudocyst which subsequently developed resolved on bowel rest and TPN. Of three who presented with bilious vomiting due to duodenal hematoma, none died; one required operative evacuation. Of five who presented with peritonitis due to duodenojejunal rupture, one died; this child presented greater than 24 hr following injury in profound septic shock. Of three who presented with hypovolemia due to moderate hemorrhage, none died; the former two were managed conservatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Injuries↗

An unusual presentation of an infected urachal cyst. Review of urachal anomalies.

An infected urachal cyst classically presents with a tender lower midline abdominal mass and systemic signs of infection, including fever, malaise, and leukocytosis. At times, the findings may be clinically confused with those of acute appendicitis, Meckel's diverticulitis, or peritonitis. Sonography aids in differentiating these entities by identifying the localized cystic mass containing debris, located anteriorly in the low mid-abdomen, extending from the region of the bladder to the umbilicus. We present an unusual case of an infected urachal cyst in a 6-year-old boy who presented with lower abdominal pain, fever, intermittent diarrhea, polyuria and dysuria, a firm, fixed left lower quadrant tender mass, and an elevated white blood cell count.

Abscess↗

The Weissenbacher-Zweymüller phenotype in the neonatal period as an expression in the continuum of manifestations of the hereditary arthro-ophthalmopathies.

The authors report the case of a female infant who presented with bilateral congenital glaucoma and myopia diagnosed at six weeks. Her facies was flat with a very low nasal bridge and a vascular nevus covering the glabellar area, micrognathia and high arched palate. The limbs appeared shorter proximally and a radiologic skeletal survey revealed dumbbell shaped long bones, flattened acetabular roofs, posterior defects in the vertebral bodies in the thoracic region, platyspondyly. Seen in follow-up at nine weeks, 14 months and 24 months, after several goniotomies which successfully controlled her intraocular pressure, she presented with high myopia, moderate hypotonia and hyperextensible joints. The midfacial hypoplasia persisted, but the skeletal X-rays showed that the long bones seem to acquire a more elongated appearance. Her mental and motor development, although five to nine months delayed, reflected regular progress. The clinical findings in this patient suggest that she belongs in the heterogeneous category of ophthalmo-arthropathies described by Weissenbacher and Zweymüller and which is thought to be the neonatal expression of the Stickler syndrome. The need for early recognition of this syndrome and a better grasp of the natural history of these disorders are emphasized in order to support the hypothesis of a continuum of manifestations of the hereditary arthro-ophthalmopathies.

Child Development↗

Malignant fibrous histiocytoma of soft tissue in childhood.

Seven children aged 6 months to 11 years with malignant fibrous histiocytoma, a type of sarcoma of soft tissues, have been treated at the Children's Hospital of Philadelphia from January 1975 through July 1983. The primary tumor arose in the head and neck region in three patients, the chest wall in two patients and the pelvis or buttock in one patient each. Operative management consisted of complete tumor removal in the two patients with chest wall tumors, and biopsy only in the remaining five children. Afterward, all seven patients were treated with a multiple-agent chemotherapy program consisting of vincristine, dactinomycin, and cyclophosphamide for two years, with or without Adriamycin (doxorubicin). The five patients with residual tumor also received radiation therapy (RT) in doses of 1500 to 5500 rad. The two children with localized, completely excised sarcoma are continuously free of tumor at 1.4 and 9 years after initiation of treatment. Of the five with residual sarcoma, three had a complete response to radiation and chemotherapy, and two of them are free of recurrence at 4 and 5 years, respectively. In the three remaining children, the tumor spread regionally into the central nervous system or distantly into the lungs, subcutaneous tissues, and liver. Childhood malignant fibrous histiocytoma of soft tissue appears to be similar to childhood rhabdomyosarcoma in its modes of spread and response to management. Operative removal is the key to successful therapy. The roles of multiple-agent chemotherapy and RT remain to be defined. Adriamycin appears to be the most promising single agent. In the absence of concrete data, it seems prudent to follow the same guidelines for irradiation as those used for other soft tissue sarcomas of childhood.

Antineoplastic Combined Chemotherapy Protocols↗

Effectiveness and efficiency of criterion testing versus interviewing for collecting functional assessment information.

This exploratory study investigated two factors believed to influence the efficiency (cost/time) and effectiveness (accuracy/validity) of functional assessment, client's level of functioning, and complexity of the skill items. The results show that cost depends on the mode of assessment; criterion testing was found to be more than twice as expensive as interviewing the client's caretakers. The effectiveness or accuracy of the assessment was found to be enhanced under two sets of circumstances: when clients were functioning at a higher level and when assessment items were less complex. The findings have implications for developing client assessments that are both efficient and effective.

Adult↗