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Biomedical subjects

D O'Brien

Publications and source records attributed to D O'Brien.

At least 37 records · Page 2Linked to original sources
PubMed1997

Humour in midwifery.

Explore the source record for details and available documents.

Adaptation, Psychological↗
PubMed1996

Anti-CD8 treatment reduces the severity of inflammatory arthritis, but not vasculitis, in mercuric chloride-induced autoimmunity.

Mercuric chloride (HgCl2) induces a T cell-dependent autoimmune syndrome in Brown-Norway (BN) rats characterized by a humoral response, tissue injury with an accumulation of CD8+ and CD4+ T cells, and an increase in tissue IL-4 mRNA and serum IgE suggesting Th2 cell activation. In other models of autoimmune disease, CD8+ cells act in both anti- and pro-inflammatory capacities, suggesting that functionally distinct CD8+ populations exist in vivo. The effect of treatment with OX8, a depleting anti-CD8 MoAb, on the initiation of HgCl2-induced autoimmunity was assessed in two experiments in a total of 20 BN rats, and compared with 20 animals treated with a control MoAb or PBS. OX8 significantly depleted peripheral blood CD8+ lymphocytes, had no effect on HgCl2-induced anti-collagen or myeloperoxidase antibodies, nor on the incidence or severity of caecal vasculitis. The severity of HgCl2-induced arthritis was significantly reduced in OX8-treated animals; median peak score reduced from 7.5 to 3.0 (experiment 1) and from 7.0 to 4 (experiment 2) (P = 0.009, Mann-Whitney U-test). OX8 treatment also exacerbated the early rise in HgCl2-induced IgE and induced a significant rise in plasma interferon-gamma (IFN-gamma), suggesting that CD8+ cells may have a regulatory influence on Th cell populations. These data provide direct evidence that CD8+ cells may act in a proinflammatory capacity in both this model of autoimmunity and the pathogenesis of inflammatory arthritis.

Animals↗
PubMed1995

High-performance liquid chromatographic assay of plasma thalidomide: stabilization of specimens and determination of a tentative therapeutic range for chronic graft-versus-host disease.

Thalidomide is now widely used to treat chronic graft-versus-host disease, but its use is associated with non-teratogenic side effects such as peripheral neuropathy. To examine the value of monitoring plasma concentrations of the drug in such patients, we have developed a high-performance liquid chromatographic (HPLC) assay. The method uses 0.5 mL plasma, is linear to 10 mg/L and had a detection limit of 0.2 mg/L. Thalidomide in plasma specimens was unstable at physiological pH but could be stabilized for several weeks by simple acidification. We describe a protocol for monitoring patients treated with thalidomide which permits convenient transportation and storage of specimens and report, provisionally, that plasma concentrations in the range 1-7 mg/L are therapeutically effective in chronic graft-versus-host disease without adverse side effects.

Chromatography, High Pressure Liquid↗
PubMed1995

Serum levels of selected liver proteins following partial hepatectomy in the female rat.

Liver regeneration in the rat following partial hepatectomy (PH) is a frequently used model to study regulatory mechanisms in relation to cell growth and differentiation. In the present study, we analysed quantitative changes in the peripheral circulation of a number of important serum proteins following PH and laparotomy. Alpha-fetoprotein synthesis was induced in the PH rats and remained at very low levels in non-operated controls. Pregnancy-associated murine protein-1 levels and fibronectin levels were lower in the circulation of all operated animals compared with the intact controls. The serum levels of alpha-2 macroglobulin were elevated in all operated animals compared with the non-operated controls. Circulating complement factors C3c and C4 were present at significantly lower levels in PH animals than in rats following laparotomy. Small growth stimulating molecules (< 10 kDa) synthesized by different organs during the regenerative process have been described in the literature, but dialysates of the spleen and liver from non-operated rats and PH rats showed no significant impact on serum levels of the proteins in the present study.

Animals↗
PubMed1994

Central sympathetic control of spinal endothelin release in the rat.

Endothelin and its receptors have been identified in the spinal cord. Intrathecal administration of endothelin-3 produces hypotension in anesthetized rats. The present study was designed to identify whether endothelin-3 is released upon changes in sympathetic nervous activity. Endothelin-3-like immunoreactivity in spinal superfusates was directly correlated with resting arterial pressure. Endothelin-3 levels were enhanced by hypothalamic stimulation and by hemorrhage-induced hypotension and reduced by nitroprusside-induced hypotension. These findings suggest that sympathetic activation enhances endothelin-3 release but that nitroprusside may act directly to suppress release. We propose that endothelin-3 plays a role in spinal regulation of sympathetic outflow.

Anesthesia↗
PubMed1994

Evaluation of cold-adapted, reassortant influenza B virus vaccines in elderly and chronically ill adults.

The safety and immunogenicity of two recent cold-adapted reassortant influenza B viruses were evaluated in persons at high risk for influenza-related morbidity and mortality. Ambulatory adults > 65 years old or with chronic high-risk conditions were randomly assigned to receive parenteral trivalent inactivated influenza vaccine containing either influenza B/Ann Arbor/86 or B/Yamagata/88 hemagglutinin antigens, cold-adapted reassortant influenza B/Ann Arbor/1/86 or B/Yamagata/16/88 viruses (10(7.2) TCID50), or placebo in double-blind fashion. Cold-adapted vaccine viruses were well tolerated, with similar rates of respiratory symptoms in all groups. There were no changes in spirometry or oxygen saturation following vaccination. Immune responses to both types of vaccine were modest, with serum antibody responses occurring significantly more frequently and with higher magnitude in those receiving inactivated than in those receiving cold-adapted vaccine. Cold-adapted, reassortant influenza B vaccines are safe in the elderly and those with chronic illness but are not optimally immunogenic in this group.

Aged↗
PubMed1994

Detection of Aeromonas salmonicida, causal agent of furunculosis in salmonid fish, from the tank effluent of hatchery-reared Atlantic salmon smolts.

The fish pathogen, Aeromonas salmonicida, could be detected only by bacteriological culture from the kidney of dead or moribund fish in one tank in a hatchery rearing Atlantic salmon (Salmo salar L.) smolts. However, by using a DNA probe specific for this species, allied to a PCR assay, the pathogen could be detected in water, feces and effluent samples taken from this fish tank. Also, the presence of the pathogen was found in effluent samples from two fish tanks containing apparently healthy fish. Subsequently, the presence of pathogen in these tanks was confirmed by an increase in the daily mortality rate and by a plate culture from moribund fish.

Aeromonas↗
PubMed1994

Factor VIIa and other haemostatic variables following bone marrow transplantation.

Hepatic venocclusive disease causes considerable morbidity and mortality following bone marrow transplantation. There are two hypotheses regarding the aetiology of this syndrome; firstly that changes in plasma coagulation factors and natural anticoagulants lead to a prothrombotic state and secondly that endothelial cell activation stimulates intravascular deposition of fibrin. We have investigated these mechanisms by measuring the changes in proteins C and S and factors VII and X in the post transplant period and by using the plasma concentration of factor VIIa as an in vivo marker of potential endothelial cell tissue factor expression. Protein C fell in both allograft and autograft patients but more so in the allografts. Similar results were found for factors VII and X. These changes were predominantly due to hepatic dysfunction induced by the chemo-radiotherapy. Factor VIIa levels were unchanged in both the allograft and autograft patients. We conclude that there is no convincing evidence for a procoagulant state following BMT as there are both anticoagulant and procoagulant changes. The absence of any changes in factor VIIa levels suggests that tissue factor was not exposed to the general circulation following BMT but does not exclude focal expression at the sites of thrombosis.

Bone Marrow Transplantation↗
PubMed1994

Replication of a managed health care initiative for people with mental retardation living in the community.

To improve understanding of the cost-effectiveness of a managed health care program for individuals with mental retardation, we have described financing, utilization, and outcomes of the Developmental Disabilities Center at Morristown Memorial Hospital. The costs and benefits of health care coordination, a key feature of this program, were discussed. Under this model, annual, unreimbursed costs of health care coordination in 1989 averaged $668 for people with severe mental retardation. However, the total reimbursable costs of inpatient care were reduced. In addition, medical outcome data from ongoing research projects suggest that the program has been an important vehicle for improving the health of people with mental retardation in the community. The costs, revenues, and financing of this program were presented in order to assist candidate sites in the replication of this model. The role of this type of program in health care reform was discussed.

Community Mental Health Services↗
PubMed1994

Occipital condylar dysplasia in two Jacob sheep.

Two young Jacob sheep which presented with severe ataxia and torticollis had abnormally formed atlanto-occipital joints. Postmortem examination revealed marked dissimilarity in size between the left and right occipital condyles, with reduction in size of the foramen magnum. The atlantoaxial joint and dens were normally formed, and were not abnormally positioned in radiographs taken of one lamb. Histological evaluation of the cervicomedullary junction demonstrated extensive loss of axons and myelin, gliosis, and mild hydromyelia in one lamb.

Animals↗
PubMed1993

A Null mutation in the vasopressin V2 receptor gene (AVPR2) associated with nephrogenic diabetes insipidus in the Hopewell kindred.

Congenital nephrogenic diabetes insipidus (DIR) is a rare X-linked hereditary disorder in which the renal collecting duct is unresponsive to arginine vasopressin; thus, the urine is consistently hypotonic to plasma. Recently, the association between the V2 receptor gene (AVPR2) and DIR has been proven. We have determined the gene sequence of four family members, from three generations, of a large North American family with CNDI who were originally part of the study used to formulate the Hopewell hypothesis. It had been proposed that a single DIR gene defect was introduced to North America by a member of an Ulster Scot kindred arriving on the ship Hopewell in 1761. DNA sequencing of the AVPR2 has identified a single base transversion from G-->A which changes tryptophan 71 to a stop codon in affected patients. This point mutation causes a truncation of the receptor leading to an essentially null allele. These data and other recently described mutations in the AVPR2 in North American pedigrees, descended from Ulster Scot ancestors and other origins, make the assertion of a founder effect proposed in the Hopewell hypothesis invalid.

Amino Acid Sequence↗
PubMed1993

Epstein-Barr virus in normal, pre-malignant, and malignant lesions of the uterine cervix.

AIM--To detect the presence or absence of Epstein-Barr virus (EBV) in cervical lesions ranging from normality to invasive malignancy. METHODS--Eighteen randomly selected cases of invasive squamous cell carcinomas of the uterine cervix were examined as well as 25 cases each of normal cervices and those showing cervical intra-epithelial neoplasia (CIN) I, II, and III. DNA-DNA in situ hybridisation, using a biotinylated probe to the Bam H1 "W" fragment of EBV, was carried out in addition to the polymerase chain reaction using specific primer sequences that flank a 153 base pair segment of the Bam H1 "W" region of the EBV genome and which do not cross-amplify other DNA herpes viruses. Positive control material included paraffin wax embedded P3 HR1 lymphoblastoid cells (containing high copy numbers of EBV) and two nasopharyngeal carcinomas positive for EBV. RESULTS--Neither normal nor CIN I tissue was positive. Eight per cent of CIN II tissue was positive; 8% of CIN III, and 43% of carcinomas were positive for EBV. CONCLUSION--The study shows that the virus is present in some cases of cervical carcinoma and to a lesser degree in some premalignant lesions of the cervix, but the exact association between it and cervical oncogenesis, be it causative or incidental, remains to be determined.

Base Sequence↗