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Biomedical subjects

J O'Malley

Publications and source records attributed to J O'Malley.

72 records · Page 4Linked to original sources
PubMed1982

Intrathecal interferon in multiple sclerosis.

Human fibroblast interferon (IFN-beta) was administered by serial lumbar puncture to ten patients with multiple sclerosis (MS). Their clinical courses were compared with those of ten MS control patients who did not receive IFN-beta. As of this writing, the recipients have been followed up for 1.8 to 2.0 years (mean, 1.9 years), and the controls for 1.5 to 1.7 years (mean, 1.6 years). During the study, two recipients suffered four exacerbations, and six controls suffered 11 exacerbations. The recipients' rates of exacerbation during the study were significantly less than their rates both for the entire prestudy duration of the disease and for the 1.8 to 2.0 years immediately preceding entry into the study. The controls' rates of exacerbation before the study and during the study period did not differ significantly. Clinically, the conditions of five recipients and two controls improved, those of three recipients and four controls were unchanged, and those of two recipients and four controls worsened. Headaches, sometimes accompanied by fever and rarely by nausea and vomiting, occurred after injections of IFN-beta. Toxic symptoms usually disappeared within 24, hours; rarely, they persisted for seven to ten days. Each recipient had transient CSF pleocytosis and elevated levels to total protein (the latter remaining elevated in seven). These findings show that intrathecal administration of IFN-beta is feasible in patients with MS, warrant cautious optimism that intrathecal IFN-beta may be effective in altering the course of the disease, and support concepts of a viral or dysimmune cause of MS.

Adolescent↗
PubMed1981

Intrathecal interferon reduces exacerbations of multiple sclerosis.

Ten patients with multiple sclerosis who were treated with human fibroblast interferon (IFN-B) for 6 months showed a significant reduction in their exacerbation rates compared with their rates before treatment (P < .01). The IFN-B was administered intrathecally by serial lumbar punctures. There was no significant change in the exacerbation rates of ten multiple sclerosis control patients before and during the period of observation. The IFN-B recipients have now been on the study a mean of 1.5 years, the controls, 1.2 years. The clinical condition of five of the IFN-B recipients and one of the control patients has improved, whereas the condition of five of the controls and one of the IFN-B recipients has deteriorated (P < .036). These findings warrant cautious optimism about the efficacy of intrathecal IFN-B in altering the course of multiple sclerosis and support concepts of a viral or dysimmune etiology of the disease.

Adolescent↗
PubMed1979

Cell-mediated immunity to varicella-zoster virus infection in subjects with lymphoma or leukemia.

Normal subjects and patients with lymphoma or leukemia were tested for the levels of lymphocytes, E-rosette--forming T-cells, serum and vesicle fluid interferon, and specific in vitro proliferative response to varicella-zoster antigen after clinical varicella or herpes zoster illness. The effect of polyinosinic acid/polycytidilic acid on the immune response was also evaluated. The development of VZ specific cell-mediated response in normal subjects was characterized by intense proliferative activity eight to ten days after the onset of illness, with significant decline 70 to 80 days later. The responses in subjects with lymphoma or leukemia were much lower. Few subjects with chickenpox or zoster with lymphoma or leukemia died during the infection. Death was associated with significant depletion of E-rosette--forming T-cells, and grossly deficient specific cellular response to VZ antigen. Treatment with Poly IC frequently induced elevations in serum as well as vesicle fluid interferon levels, and increased the proliferative activity of lymphocytes against VZ antigen.

Adolescent↗
PubMedDate not supplied

Molecular networks perturbed in a developmental animal model of brain injury.

Methylazoxymethanol (MAM) is widely used as a developmental neurotoxin and exposure to its glucoside (i.e., cycasin) is associated with the prototypical neurological disorder western Pacific ALS/PDC. However, the specific molecular targets that play a key role in MAM-induced brain injury remain unclear. To reveal potential molecular networks targeted by MAM in the developing nervous system, we examined characteristic phenotypic changes (DNA damage, cytoarchitecture) induced by MAM and their correlation with gene expression differences using microarray assays (27,648 genes). Three day-old postnatal C57BL/6 mice (PND3) received a single injection of MAM and the cerebellum and cerebral cortex of PND4, 8, 15, and 22 mice were analyzed. DNA damage was detected in both the cerebellum (N7-mGua, TUNEL labeling) and cerebral cortex (N7-mGua) of PND4 mice, but progressive disruption of the cytoarchitecture was restricted to the cerebellum. A majority (>75%) of the genes affected (cerebellum 636 genes, cortex 1080 genes) by MAM were developmentally regulated, with a predominant response early (PND4) in the cerebellum and delayed (PND8 and 15) in the cerebral cortex. The genes and pathways (e.g., proteasome) affected by MAM in the cerebellum are distinct from cortex. The genes perturbed in the cerebellum reflect critical cellular processes such as development (17%), cell cycle (7%), protein metabolism (12%), and transcriptional regulation (9%) that could contribute to the observed cytoarchitectural disruption of the cerebellum. This study demonstrates for the first time that specific genes and molecular networks are affected by MAM during CNS development. Further investigation of these targets will help to understand how disruption of these developmental programs could contribute to chronic brain injury or neurodegenerative disease.

Animals↗
PubMedDate not supplied

Comparison of acute endotoxin-induced lesions in A/J and C57BL/6J mice.

Resistance to the action of endotoxin varies among inbred strains of mice, indicating that a component of this resistance has a genetic basis. Different responses to endotoxin that are characteristic of individual inbred strains represent phenotypes that can be used to genetically map the response modifier genes. This study compares the acute histologic lesions in 8-week-old male A/J and C57BL/6J (B6) mice injected intraperitoneally with endotoxin of E. coli O265:B6 (15 mg/kg). Animals of both strains exhibited splenitis, splenic lymphoid hyperplasia, splenic lymphoid necrosis, and sequestration of neutrophils in the pulmonary alveoli. The B6 mice showed increased margination of white blood cells to the pulmonary vascular endothelium relative to A/J mice. A large number of degenerating neutrophils was observed in the liver sinusoids of most B6 animals, while this lesion was much less severe in A/J mice. This difference was quantified, demonstrating a highly significant difference in neutrophil infiltration in B6 mice relative to A/J mice. Analysis of this phenotype in F1 mice demonstrates that major genes encoding the trait are not X-linked, imprinted, or maternally inherited and do not show the codominant inheritance expected if Lps(d) were primarily responsible. The distinctive, quantitative nature of these differences provides a useful assay for mapping genes that modify endotoxin responsiveness using the AXB and BXA recombinant inbred (RI) strains derived from A/J and B6 mice.

Animals↗
PubMedDate not supplied

Redesigning roles for patient-centered care. The hospitality representative.

Nurses cannot always meet patients' expectations for nonclinical care. The authors describe the operational redesign of several hotel-related functions to enhance the provision of nonclinical care. This system enhances care delivery to better balance patients' perceptions of the clinical with the non-clinical components of care.

Admitting Department, Hospital↗
PubMedDate not supplied

Fluid and electrolyte balance during a cool weather marathon.

Changes in blood, serum, and urine parameters that are usually associated with fluid and electrolyte balance were studied in 45 volunteers who ran the 1987 Pittsburgh Marathon. There were 39 males and 6 females. The mean age was 39.3 years. Their mean fluid intake was 1650 cc and the mean finishing time was 4 hours and 1 minute. The race was run in the rain with a temperature of 46 degrees F. When the prerace and postrace values of the runners were compared, significant increases were noted in the serum sodium, potassium, blood urea nitrogen (BUN), creatinine, uric acid, creatine phosphokinase (CPK), protein, plasma renin, vasopressin, and urinary potassium. Significant decreases were found in weight, blood pressure, and urinary sodium. No significant differences were noted in serum chloride, serum glucose, and hemoglobin/hematocrit. The mean weight loss of 1.9 kg was less than weight losses reported in marathons run under warmer conditions.

Adult↗
PubMedDate not supplied

Psychological and psychophysiological factors in prevention and treatment of cold injuries.

Cold injured patients in Alaska come from many sources. Although sport and work continues to provide large numbers of cold injured, most severe repeat injuries tend to reflect other biopsychosocial consequences. Certain behaviors can increase the probability of injury, however all persons living in cold climates are potential candidates. One can decrease risk by education, knowledge and intelligent behavior. Proper respect for adequate protection and hydration seem to be critical factors. Understanding the psychological, physiological and psychophysiological aspects of the cold environment performer helps refine the prevention and treatment strategies for cold injury. Skill training with bio-behavioral methods, such as thermal biofeedback, and the value of medical psychotherapy appear to offer continued promise by facilitating physiologic recovery from injury, as well as assisting in long term rehabilitation. Both approaches increase the likelihood of a favorable healing response by soliciting active patient participation. Medical Psychotherapy for traumatic injuries can also help identify and manage cognitive emotional issues for families and patients faced with the permanent consequences of severe thermal injuries. Thermal biofeedback therapy has the potential benefit of encouraging greater self-reliance and responsibility for self-regulating overall health by integrating self-management skills regarding physiology, diet and lifestyle. Inpatient and outpatient biofeedback training offers specific influence over vascular responses for healing, as well as providing an effective tool for pain management. Interest in cold region habitation has continued to expand our study of human tolerance to harsh, extreme environments. Biological, psychological, sociological, and anthropological views on adaptation, habituation, acclimatization, and injury in cold environments acknowledges the role of development, learning and educated responses to cold environments. The study of health, performance, and injury prevention in extreme isolated cold environments has important strategic and scientific implications. What is learned from behavioral studies of cold survival provides an opportunity to increase our scientific knowledge and understanding. These cold research findings can assist in our future exploration of cold, underwater farming at great depths, and to far distance space travel to cold planets. The relatively new research frontier "Polar Psychology" has evolved to study how interactions with cold environments can have both positive and/or negative consequences. This research simulates the psychological factors likely to be encountered while exploring isolated cold regions of distant galaxies. The psychological and psychophysiological correlates of cold experience appear to be a function of four interactive issues: the environment, genetic predisposition, learning or experience, and finally perception or cognition. Individual cold tolerance seems to relate heavily on sensation, perception and behavior.(ABSTRACT TRUNCATED AT 400 WORDS)

Acclimatization↗