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Biomedical subjects

D O'Brien

Publications and source records attributed to D O'Brien.

At least 19 recordsLinked to original sources

Th1/Th2 cytokine imbalance in meningioma, anaplastic astrocytoma and glioblastoma multiforme patients.

The balance between Th1 and Th2 cytokines is thought to be an important factor in terms of tumour prognosis. Serum samples from 61 newly diagnosed patients with brain tumours and 50 age- and sex-matched non-tumour controls were analysed by ELISA for circulating levels of interleukin-12 (IL-12p70 and p40) and interleukin-10 (IL-10); pivotal Th1 and Th2 cytokines, respectively. Patients were divided into various groups depending on their histological diagnosis: meningioma (n=11), anaplastic astrocytoma (n=4) and glioblastoma multiforme (GBM; n=46). Significant reduction in serum IL-12 was seen in all groups as compared with the controls: meningioma, p=0.03; anaplastic astrocytoma, p<0.001; and GBM, p<0.001. Conversely, serum IL-10 was significantly increased in anaplastic astrocytoma, p=0.02, and GBM, p=0.03. The changes in the serum cytokines were not caused by the effects of steroids, as sequential analysis of patients pre- and post-steroid treatment commencement showed no difference. This study shows that patients with advanced primary intracranial malignancies have decreased circulating IL-12 and increased circulating IL-10, demonstrating that brain tumours have a major systemic effect on the immune system.

Adult↗

Haemolytic uraemic syndrome associated with interfamilial spread of E. coli O26:H11.

In September 2000, haemolytic uraemic syndrome (HUS) was diagnosed in a 10-month-old child with a prodromal history of vomiting and diarrhoea (non-bloody). Investigation revealed that a self-limiting gastrointestinal illness (mean duration 48 h) had occurred among immediate and extended family in the 2 weeks prior to the child's admission. The epidemiology of the illness suggested person-to-person spread. Five children (close family contacts) had E. coli O26 verocytotoxin (VT1 and VT2) isolated from stools. Stool culture and serology from the index case were negative for shiga toxin-producing E. coli (STEC) organisms. Control measures in accordance with the Public Health Laboratory Service (PHLS), verocytotoxogenic organisms (VTEC) guidelines were applied to prevent further spread among the extended family and contacts. Despite detailed food and environmental exposure histories, the source of the illness was not identified. This incident highlights the importance of investigation of cases of post-diarrhoeal HUS, for potential shiga toxin E. coli aetiology.

Diarrhea↗

Candida glabrata prosthetic valve endocarditis treated successfully with fluconazole plus caspofungin without surgery: a case report and literature review.

Reported here is the case of a 72-year-old man who was diagnosed with Candida glabrata prosthetic mitral valve endocarditis and treated successfully with fluconazole plus caspofungin after he refused and was determined unfit for surgery. Initial treatment with intravenous amphotericin B resulted in acute renal impairment. Despite 8 days of intravenous fluconazole therapy, he remained fungemic. Caspofungin was added to the treatment regimen with subsequent sterilisation of blood culture. The patient was treated for 34 days with caspofungin and 41 days with fluconazole. He continued oral fluconazole after hospital discharge and remained well at follow-up 11 months later. The role of fluconazole and caspofungin in the treatment of Candida endocarditis is discussed.

Acute Kidney Injury↗

Paraganglioma of the filum terminale.

Paraganglioma of the filum terminale is rare. The authors report a case of paraganglioma of the filum terminale presenting with paraparesis on a background of spastic quadriparesis. The clinical presentation, radiological findings and current literature are presented.

Biomarkers, Tumor↗

Sensitivity of quantum-dot semiconductor lasers to optical feedback.

The sensitivity of quantum-dot semiconductor lasers to optical feedback is analyzed with a Lang-Kobayashi approach applied to a standard quantum-dot laser model. The carriers are injected into a quantum well and are captured by, or escape from, the quantum dots through either carrier-carrier or phonon-carrier interaction. Because of Pauli blocking, the capture rate into the dots depends on the carrier occupancy level in the dots. Here we show that different carrier capture dynamics lead to a strong modification of the damping of the relaxation oscillations. Regions of increased damping display reduced sensitivity to optical feedback even for a relatively large alpha factor.

Journal Article↗

Bowel evisceration.

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Endometrial Neoplasms↗

A twelve-year review of central nervous system bacterial abscesses; presentation and aetiology.

OBJECTIVES: To review and document the changing patterns in diagnosis, causes and treatment of bacterial infections of the central nervous system (CNS) in a national neurosurgical unit only in patients from whom a specimen was obtained for culture. METHODS: The case notes, radiological results and laboratory records of all 163 patients in our institution who underwent a neurosurgical procedure between 1988 and 2000 for a CNS abscess in a national center were reviewed retrospectively. Those patients from whom there were no operative specimens (i.e. neurosurgical intervention was not performed) and who were treated empirically were excluded, as were patients with mycobacterial infection. RESULTS: The mean age of the 163 patients was 35.2 years. Headache, pyrexia and an altered mental state were the commonest presentations. The frontal lobe was the commonest anatomical site (62 patients, 38%) and the majority of abscesses occurred following community infections such as sinusitis and mastoiditis; no primary source could be identified in 32 (20%) patients. Bacteria were isolated from 73% of patients and polymicrobial infections occurred in 29 (17.7%) patients. Anaerobes accounted for only 13.6% of isolates and methicillin-resistant Staphylococcus aureus (MRSA) was isolated on five occasions, all in the last five years of this review. Sixteen (9.8%) patients died prior to discharge or transfer back to the original referring hospital and 18 (11%) patients developed epilepsy. CONCLUSION: There was a relatively high incidence of polymicrobial infection but the number of specimens with anaerobes was small, which may be because of the use of empiric metronidazole before surgical intervention. Most infections were community-acquired and responded well to a combination of surgical drainage and antibiotic therapy. The emergence of MRSA in this group of patients is, however, worrying.

Adolescent↗

Fever in returned travelers: review of hospital admissions for a 3-year period.

We reviewed 232 consecutive patients admitted to a tertiary-care hospital under the care of an infectious diseases unit for management of febrile illness acquired overseas. A total of 53% presented to hospital within 1 week of return and 96% within 6 months. Malaria was the most common diagnosis (27% of patients), followed by respiratory tract infection (24%), gastroenteritis (14%), dengue fever (8%), and bacterial pneumonia (6%). Pretravel vaccination may have prevented a number of admissions, including influenza (n=11), typhoid fever (n=8) and hepatitis A (n=6). Compared to those who had not traveled to Africa, those who had were 6 times more likely to present with falciparum than nonfalciparum malaria. An itinerary that included Asia was associated with a 13-fold increased risk of dengue, but a lower risk of malaria. Palpable splenomegaly was associated with an 8-fold risk of malaria and hepatomegaly with a 4-fold risk of malaria. As a cause of fever, bacterial pneumonia was > or =5 times more likely in those who were aged >40 years.

Adult↗

A Phase 1 study of a recombinant viruslike particle vaccine against human papillomavirus type 11 in healthy adult volunteers.

Viruslike particles (VLPs) produced from the L1 protein of several papillomaviruses have induced protection from infection after live challenge in animal models. In the present study, the safety and immunogenicity of a human papillomavirus (HPV)--11 L1 VLP candidate vaccine were measured in a phase 1, dose-finding trial in humans. The vaccine was well tolerated and induced high levels of both binding and neutralizing antibodies. Marked increases in lymphoproliferation to HPV--11 L1 antigens were noted after the second vaccination. In addition, lymphoproliferation was induced after vaccination in peripheral blood mononuclear cells (PBMC) stimulated with heterologous L1 VLP antigens of HPV types 6 and 16. Statistically significant increases in HPV antigen--specific interferon--gamma and interleukin-5 production were measured from PBMC culture supernatants. This candidate HPV VLP vaccine induced robust B and T cell responses, and T cell helper epitopes appear to be conserved across HPV types.

Adolescent↗

Safety and immunogenicity of a recombinant hemagglutinin vaccine for H5 influenza in humans.

Recent outbreaks of avian influenza in humans have demonstrated the need for vaccines for influenza viruses with pandemic potential. Recombinant hemagglutinins are an attractive option for such vaccines because they do not require handling potentially highly pathogenic influenza viruses for vaccine production. In order to evaluate the immunogenicity, optimum dosing and timing of administration of a recombinant baculovirus-expressed H5 HA (rH5) in humans, 147 healthy adults were assigned randomly to receive intramuscular rH5 as two doses of 25, 45 or 90 microg each, one dose of 90 microg followed by a dose of 10 microg, or two doses of placebo, at intervals between doses of 21, 28 or 42 days. All doses of rH5 were well tolerated. The rH5 vaccine was modestly immunogenic at high dose. Neutralizing antibody responses to a titer of 1:80 or greater were seen in 23% (14/60) of individuals after a single dose of 90 microg, and in 52% (15/29) after two doses of 90 microg. Varying intervals between doses from 21 to 42 days had no significant effect on antibody responses to vaccination. These results suggest that baculovirus-expressed H5 HA can induce functional antibody in individuals who have not had prior exposure to H5 viruses, but that further studies to improve the immunogenicity of the vaccine are needed.

Adult↗

Neural correlates of maternal separation in rhesus monkeys.

BACKGROUND: The neurobiological basis of stress and anxiety in primates remains poorly understood. In this study, we examined the neural response to a naturalistic social stressor: maternal separation. We used rhesus monkeys as an animal model because of their close phylogenetic affinity with humans. METHODS: Six juvenile rhesus monkeys received [(18)F]-fluorodeoxyglucose positron emission tomography scans following 1) a period together with their mothers and again after separation from their mothers 2) with or 3) without visual contact. Image subtraction revealed brain regions that exhibited altered activity during separation. In addition, plasma cortisol concentrations obtained following each condition were tested for correlations with regional brain activity. RESULTS: Maternal separation activated the right dorsolateral prefrontal cortex and the right ventral temporal/occipital lobe. There was also decreased activity in left dorsolateral prefrontal cortex associated with separation stress. Correlational analyses demonstrated these activated and deactivated regions to be positively and negatively correlated with cortisol, respectively. Additionally, correlational analyses revealed cortisol-related activation in brainstem areas previously implicated in stress and anxiety. CONCLUSIONS: In juvenile rhesus monkeys, the stress of maternal separation is associated with activation in the right dorsolateral prefrontal cortex and ventral temporal/occipital lobes and decreased activity in the left dorsolateral prefrontal cortex.

Aggression↗

Community attitudes towards performing cardiopulmonary resuscitation in Western Australia.

OBJECTIVE: to determine the attitudes of the Western Australian community towards performing cardiopulmonary resuscitation, and the factors affecting these attitudes. METHODS: telephone survey of a randomly selected sample of people from suburban Perth and rural Western Australia; practical assessment of a sub-sample of volunteers from those surveyed, to correlate survey answers with practical skills. RESULTS: of 803 people surveyed, the majority (90.7%) definitely would give mouth-to-mouth ventilation to a friend or relative, but less than half (47.2%) would to a stranger. The reluctance was mostly (56%) because of health and safety concerns, particularly related to HIV infection. Higher percentages of people would definitely provide cardiac massage for a friend or relative (91.4%) or stranger (78.1%). People were more likely to give mouth-to-mouth and cardiac massage if they had been trained in cardiopulmonary resuscitation (CPR), trained several times, trained recently, and used their CPR skills in real life. There were no significant differences between city and country people in whether they would provide CPR, but older people were less willing to provide mouth-to-mouth or cardiac massage. On practical assessment of 100 volunteers, there were significant errors and omissions in airway assessment, mouth-to-mouth resuscitation and cardiac massage. Volunteers with better practical scores were more prepared to provide CPR. DISCUSSION: our results indicate a significant reluctance of the Western Australia public to perform mouth-to-mouth, except to a friend or relative. Earlier CPR training, practice and use seemed to diminish this reluctance. Practical CPR skills were not well executed. Those with better skills were less reluctant to use them. We recommend increasing CPR training in the community, greater frequency of refresher courses and public education on the risks of CPR to improve rates of bystander CPR.

Attitude to Health↗

Early development of rat ventral root transitional zone: an immunohistochemical and morphometric study.

Bundles of ventral motoneuron axons cross the white matter of the spinal cord, emerge through the cord surface at the CNS-PNS transitional zone (TZ) and continue in the PNS as ventral rootlets. This study identifies immunohistochemical and morphometric changes which characterise the key events in early TZ formation in the rat. E18 is a landmark stage, since it is then that the major events of TZ differentiation are initiated. In the glial processes associated with the TZ, vimentin expression decreases, while that of GFAP increases. In the proximal rootlets the transient expression of CNS markers such as GFAP and of neural adhesion molecules such as HNK-1/N-CAM begin to decrease. Their resulting differential expression clearly defines the CNS-PNS interface. These changes coincide with the arrival of glial nuclei at the TZ. Cell clusters which appear on proximal ventral rootlet surfaces shortly after their emergence from the cord, have by E18 formed an extensive matrix of processes which segregates the axon bundle. This comprises the earliest of two well-defined barriers across the axon bundle. An important function may be to prevent Schwann cell invasion of the cord. Cluster cells display some immunohistochemical features in common with Schwann cells. The second barrier becomes fully established only at P2 and forms the definitive CNS-PNS interface. It consists of processes arising from astrocytes surrounding the TZ. Changes in the nuclear density of the cell types correspond closely to their segregating activity. The immunohistochemical and ultrastructural changes complement one another to deepen and enhance understanding of TZ development.

Animals↗

Bein' lazy.

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Clinical Competence↗