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Biomedical subjects

T O'Neill

Publications and source records attributed to T O'Neill.

15 recordsLinked to original sources

Serological responses of specific pathogen-free foals to equine herpesvirus-1: primary and secondary infection, and reactivation.

Serum antibody (virus neutralisation, complement fixation, IgM and IgG) responses to equine herpesvirus-1 (EHV-1) infection were measured in six foals which were initially free from EHV-1 and EHV-4 infection and maternally-derived antibodies. Following primary infection, high titres of virus neutralisation and complement fixation antibodies were detectable against EHV-1, however, corresponding antibody levels against EHV-4 were low or inapparent, although the two viruses share a number of cross-reactive epitopes. In addition, following the primary infection with EHV-1, IgM levels increased before those of IgG, virus neutralisation and complement fixation antibodies, peaked sooner and thereafter declined. Stimulation of IgM levels was observed on secondary infection with EHV-1 given 61 days later. In contrast, IgG, virus neutralisation and complement fixation antibodies following primary infection were more sustained and no increase in their levels was observed on secondary infection. No consistent changes in IgM or IgG levels were seen after administration of dexamethasone to reactivate latent virus.

Animals

Integration of cell culture with continuous, on-line sterile downstream processing.

The development of an integrated system for the continuous, automated production of pure cell culture derived proteins is discussed. The system comprises a cell culture subunit for the continuous culture of mammalian cells and a purification subunit linked on-line to the cell culture subunit. The cells are compartmentalized and continuously perfused with culture medium. The cell culture medium leaving the bioreactor is perfused through a sterile immunoaffinity column that instantaneously removes the product from the culture fluid. This results in improved product quality because the product is quickly removed from the cell culture, thus minimizing contact with degradative enzymes. The culture medium, stripped from the secreted product, is recirculated into the bioreactor. The system allows simple, automated, and economical production of purified proteins with higher quality than that possible with current production methods. The integration also allows on-line, real-time process monitoring, thus simplifying process development and allowing more consistent production of biologics.

Animals

Maturation of human immunodeficiency virus particles assembled from the gag precursor protein requires in situ processing by gag-pol protease.

The vaccinia virus expression system was used to determine the role of human immunodeficiency virus type 1 (HIV-1) protease in viral morphogenesis and maturation. The unprocessed p55 gag precursor polyprotein alone was assembled to form HIV-1 particles which budded from cells. The particles were spherical and immature, containing an electron-dense shell in the particle submembrane; there was no evidence of core formation. Expression of both gag and pol proteins from a recombinant containing the complete gag-pol coding sequences resulted in intracellular processing of gag-pol proteins and the production of mature particles with electron-dense cores characteristic of wild-type HIV virions. To ascertain the role of protein processing in particle maturation, the pol ORF in the gag-pol recombinant was truncated to limit expression of the pol gene to the protease domain. With this recombinant expressing p55 gag and protease, intracellular processing was observed. Some of the resultant particles were partially mature and contained processed gag protein subunits. In contrast, particle maturation was not observed when the HIV-1 protease and p55 gag were coexpressed from separate recombinants, despite evidence of intracellular gag processing. These findings suggest that HIV-1 protease must be an integral component of the full-length gag-pol precursor for optimal processing and virion maturation.

Fusion Proteins, gag-pol

Protection against lethal equine herpes virus type 1 (subtype 1) infection in hamsters by immune stimulating complexes (ISCOMs) containing the major viral glycoproteins.

An experimental ISCOM vaccine has been prepared from gradient purified equine herpes virus type 1 (EHV-1). Radiolabelling studies demonstrated that this vaccine contained all the major viral glycoproteins in relative amounts similar to those found in non-detergent disrupted viral preparations. This EHV-1 ISCOM vaccine generated fully protective responses in hamsters challenged with an otherwise lethal dose of the hamster-adapted EHV-1 strain RACH.

Adjuvants, Immunologic

An evaluation of an anticoagulant clinic.

Patient comprehension of the risks of anticoagulation, tablet recognition skills and knowledge of complications of warfarin therapy were evaluated in 160 patients attending the anticoagulant clinic in a central Dublin teaching hospital group. Potential complications from over- and under- dosage with warfarin were unknown to 119 (74%) and 97 (60%) patients respectively. 1, 3 and 5 mg tablets could not be identified by 40 (25%), 55 (34%) and 60 (37%) patients respectively. The current prescribed dose could not be recollected by 31 (19%) patients. Haemorrhagic complications occurred in 23 (14%) subjects over one year, four of whom required hospital admission and two blood transfusions. No thromboembolic episodes were noted. This study reveals a widespread lack of understanding of anticoagulation and its potential complications in patients receiving warfarin therapy and has led to a critical reappraisal of patient education, patterns of referral and supervision of such individuals in our clinic.

Female

Postnatal depression--aetiological factors.

One hundred and forty-two women at six weeks postpartum were asked to complete Cox's Edinburgh Postnatal Depression Scale. Thirty-eight scored positively for depression and 28 of these were followed up by a psychiatrist. Twenty-eight controls were randomly selected from those who scored negatively. Numerous variables were considered, including the type of labour, whether the mother was breastfeeding or not, and the presence or absence of a psychiatric history. In addition the depressed group completed the Eysenck Personality Inventory. A past psychiatric history was found to be a very significant risk factor and there is a definite association between postnatal depression and delivery by forceps, vacuum or caesarian section. Maternal age and breastfeeding were not found to be of aetiological significance.

Depression

Fatal aplastic anaemia following prolonged diclofenac use in an elderly patient.

Aplastic anaemia is recognised to occur following the use of some non-steroidal anti-inflammatory drugs. We report a case of fatal aplastic anaemia following prolonged administration of diclofenac in a 77 year old lady with rheumatoid arthritis. To our knowledge this is the first report of fatal aplastic anaemia associated with diclofenac use in an elderly patient.

Aged

Antibody isotype responses in the serum and respiratory tract to primary and secondary infections with equine influenza virus (H3N8).

Serum antibody (IgGab, IgM and IgA) responses to primary and secondary infection with influenza A/equine/Newmarket/79 (H3N8) by nebulised aerosol were compared with local (nasopharyngeal and tracheal) antibody responses in ponies. Circulating IgGab antibody was of long duration after primary infection, whereas IgM responses were short-lived after both primary and secondary infections. The antigenic stimulation of secondary infection with equine influenza was sufficient to induce elevations of serum IgM and IgA in the presence of high levels of circulating IgGab. These results support the potential of virus-specific IgM measurement for the detection of recent exposure to virus in horses which have high levels of circulating IgGab. Unlike serum IgGab, nasal and tracheal wash antibody of this isotype did not show long duration after primary infection, but local antibody memory was demonstrated by anamnestic responses on rechallenge. Nasopharyngeal IgA developed later than IgGab and IgM, and was more durable.

Aerosols

Immature cervical teratoma arising in one fetus of a twin pregnancy. Case report and review of the literature.

This is the first recorded case of an immature cervical teratoma arising in one fetus of a twin pregnancy. Although real-time ultrasound detected the presence of an abnormality, its true nature was not established until after histological examination. Extra-amniotic prostaglandin pregnancy termination was performed at 20 weeks' gestation due to the onset of acute hydramnios and the rapid increase in tumor size. Delivery of both fetuses was performed under general anesthesia. Extraction of the abnormal twin was only possible after the tumor was separated off from the fetal neck in utero.

Abortion, Induced

Myocardial hypertrophy, fibrosis and infarction following exposure of the heart to radiation for Hodgkin's disease.

A 35 year old man was treated for stage IIA Hodgkin's disease by radiation to the upper thorax, axillae and neck. Three years later he presented with intractable and ultimately fatal congestive heart failure. Autopsy revealed massive biventricular hypertrophy with widespread subendocardial fibrosis and myocardial infarction, but with little coronary artery disease. Such a complex of features has not previously been described after radiation therapy and cannot be adequately explained by other known causes of heart muscle disease. Ventricular hypertrophy with extensive subendocardial fibrosis may be part of the spectrum of radiation heart disease.

Adult

Successful treatment of a malignant gastrinoma with streptozotocin.

The treatment with streptozotocin of a patient with metastatic gastrinoma is described. Two courses of intravenous streptozotocin were without effect. However, three months after two doses of 4 g streptozotocin were given into the coeliac axis, there was a marked reduction in hepatic size and a fall in fasting plasma gastrin levels from 1430 pmol/l to 240 pmol/l. Seven months after treatment fasting plasma gastrin levels were 125 pmol/l.

Adenoma, Islet Cell

A case of group B streptococcal pyomyositis.

The group B streptococcus is an opportunistic pathogen that causes a variety of serious infections including bacteremias, puerperal sepsis, and neonatal meningitis. Group B streptococcal infections of muscle are rare. We report here an unusual case of group B streptococcal pyomyositis. Pyomyositis arises predominantly from infections caused by Staphylococcus aureus and, occasionally, Streptococcus pyogenes. Because of the rarity of pyomyositis in temperate climates, the common lack of localizing signs or symptoms, and the frequently negative blood cultures, considerable delay often precedes the diagnosis of pyomyositis; in fact, the infection has been initially misdiagnosed as muscle hematoma, cellulitis, thrombophlebitis, osteomyelitis, or neoplasm. Diagnosis may be greatly aided by radiologic techniques that can demonstrate the sites of muscle enlargement and the presence of fluid collections. The response to antibiotics is usually rapid, but resolution of the infection may require aspiration of deeply situated muscle abscesses. This report describes a diabetic patient with an unusual presentation of pyomyositis that mimicked an acute abdomen.

Abdomen, Acute