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Biomedical subjects

M Irwin

Publications and source records attributed to M Irwin.

At least 19 recordsLinked to original sources
PubMed2002

Suppression of interleukin-6 to interleukin-10 ratio in chronic alcoholics: association with postoperative infections.

OBJECTIVE: To investigate the interleukin-6 (IL-6) to interleukin-10 (IL-10) ratio and levels of sE-selectin in patients undergoing elective surgery of the upper digestive tract and to define the differences in the perioperative immune response between chronic alcoholic and non-alcoholic patients. DESIGN: Prospective pilot study. SETTING: Single center, interdisciplinary intensive care unit (ICU) at a university hospital. MEASUREMENT AND MAIN RESULTS: The study compared chronic alcoholics ( n=25) and non-alcoholics ( n=20) before and after surgery for resection of upper digestive tract tumors. White blood cell counts, C-reactive protein and circulating levels of sE-selectin, the pro-inflammatory cytokine IL-6 and the inhibitory cytokine IL-10, were obtained at hospital admission, preoperatively, postoperatively at ICU admission and 2 and 4 days later. Rates of postoperative infectious complications including pneumonia and sepsis were determined. sE-selectin only differed between chronic alcoholics and non-alcoholics preoperatively. Compared to non-alcoholics, chronic alcoholic patients showed a fourfold increase in circulating levels of IL-10 ( p<0.01) and a suppression of the IL-6/IL-10 ratio ( p=0.001) immediately after surgery. Coincident with the immune alterations, chronic alcoholics had a prolonged ICU stay ( p<0.01) and a threefold increased rate of wound infections ( p<0.05) and pneumonia ( p<0.01). Lower IL-6/IL-10 ratios were associated with increased rates of infectious complications ( p<0.05). CONCLUSION: Chronic alcoholics had decreased IL-6/IL-10 ratios at ICU admission and increased rates of infectious complications in the postoperative ICU course. This may indicate immediate postoperative immune suppression before the onset of infections and may help to identify chronic alcoholic patients at risk.

Aged↗
PubMed2002

Early introduction of clinical skills teaching in a medical curriculum--factors affecting students' learning.

OBJECTIVE: To evaluate the effects of the early introduction of clinical skills teaching on students' learning following an overhaul of the curriculum of a traditional Asian medical school. METHODS: Randomly selected medical students in Year I and II were invited to participate in 30 focus group interviews while all students were asked to assist with the questionnaire survey. Most students were contacted personally to help them understand the objectives of the study. Confidentiality was emphasised and a non-faculty interviewer was recruited for the interviews. RESULTS: Two hundred and eight of Year I/Year II students attended the lunchtime focus group interviews (response rate=86.7%) while 252 (73.5%) students returned the questionnaire. The majority of them (87%) agreed or strongly agreed that it was good to introduce clinical skills in the early years of the curriculum. They reflected that the course enhanced their learning interest and made them feel like doctors. They also made many constructive suggestions on how the course could be improved during the interactive focus group interviews so that the negative effects could be minimised. CONCLUSION: It is useful to introduce clinical skills in the early years of a medical curriculum. A comprehensive course evaluation, using both quantitative and qualitative methods, helps to collect useful information on how the course can be improved.

Clinical Competence↗
PubMed2001

A giant stream of metal-rich stars in the halo of the galaxy M31.

Recent observations have revealed streams of gas and stars in the halo of the Milky Way that are the debris from interactions between our Galaxy and some of its dwarf companion galaxies; the Sagittarius dwarf galaxy and the Magellanic clouds. Analysis of the material has shown that much of the halo is made up of cannibalized satellite galaxies, and that dark matter is distributed nearly spherically in the Milky Way. It remains unclear, however, whether cannibalized substructures are as common in the haloes of galaxies as predicted by galaxy-formation theory. Here we report the discovery of a giant stream of metal-rich stars within the halo of the nearest large galaxy, M31 (the Andromeda galaxy). The source of this stream could be the dwarf galaxies M32 and NGC205, which are close companions of M31 and which may have lost a substantial number of stars owing to tidal interactions. The results demonstrate that the epoch of galaxy building still continues, albeit at a modest rate, and that tidal streams may be a generic feature of galaxy haloes.

Journal Article↗
PubMed2001

Melatonin modulation of lymphocyte proliferation and Th1/Th2 cytokine expression.

Melatonin is hypothesized to play a role in neuroimmunomodulation. This study investigated the in vitro effects of melatonin (10(-12) - 10(-6) M) on human peripheral blood mononuclear cell (PBMC) proliferation and T helper type 1 and T helper type 2 (Th1/Th2) cytokine expression. In vitro doses of melatonin significantly increased PBMC proliferation (p<0.05) and decreased IL-10 production in culture supernatants (p<0.05). However, there was no effect of melatonin on the stimulated production of IFN-gamma or on the intracellular accumulation of the activation antigen CD69, IFN-gamma, or IL-10 as measured by flow cytometry. These data support the notion that physiologic doses of melatonin increase lymphocyte proliferation possibly due to decreases in production of the inhibitory cytokine IL-10.

Adolescent↗
PubMed2001

Central CRH suppresses specific antibody responses: effects of beta-adrenoceptor antagonism and adrenalectomy.

Central corticotropin releasing hormone (CRH)-induced activation of the sympathetic nervous system and/or the pituitary-adrenal axis is hypothesized to mediate suppression of in vivo specific antibody responses. To test whether beta-adrenergic receptor activation is involved in the immunosuppressive effects of central CRH, rats were pretreated with propranolol or saline before intracerebroventricular infusion of CRH and immunization with keyhole limpet hemocyanin (KLH). KLH (3 microg/kg) immunization induced significant increases in circulating levels of antigen-specific IgM and IgG. Central infusion of CRH (200 pmol) suppressed both IgM and IgG responses. Pretreatment with propranolol (20 mg/kg IP) reversed CRH-induced suppression of IgG responses but had no effect on IgM levels. To test whether adrenal activation also plays a role in the effects of KLH on specific antibody responses, a separate group of animals underwent adrenalectomy prior to CRH infusion and immunization with KLH. As compared to nonadrenalectomized control rats, adrenalectomized rats showed a reduction of antibody responses, and CRH failed to induce a further suppression of IgM or IgG responses in adrenalectomized animals. Collectively, these data suggest that beta-adrenoceptors mediate the suppression of primary antibody responses induced by central CRH. Moreover, the adrenals may promote optimal primary antibody responses after exposure to physiological levels of antigen.

Adjuvants, Immunologic↗
PubMed2001

Neuroimmunology of disordered sleep in depression and alcoholism.

The specific functions of sleep are not known, although sleep is commonly considered a restorative process that is important for the proper functioning of the immune system. Severity of disordered sleep in depressed and alcoholic subjects correlates with declines in natural and cellular immunity and is associated with alterations in the complex cytokine network. Despite evidence that sleep and sleep loss have effects on immune processes and nocturnal secretion of cytokines, the physiological significance of these immune changes is not known. Moreover, in view of basic evidence of a reciprocal interaction between sleep and cytokines, further research is needed to understand whether alterations in cytokines contribute to disordered sleep.

Alcoholism↗
PubMed2001

The use of focus group interviews in Asian medical education evaluative research.

OBJECTIVE: To evaluate the use of focus group interviews in Asian medical education evaluative research. METHODS: Randomly selected medical students were invited to participate in 30 focus group interviews to provide in-depth data about the effect on their learning of the introduction of early clinical skills. Efforts were made to meet all the students to help them understand the objectives of the focus group. Confidentiality was emphasised and a non-faculty interviewer was recruited for the interviews. RESULTS: The students considered the use of focus groups to be a more meaningful way of collecting students' opinions than other methods, for example structured questionnaire, because it allowed an interactive discussion. They also felt that having an independent non-faculty interview moderator had encouraged them to express their opinions more candidly during the interviews. CONCLUSION: The use of focus group interviews among Asian medical students for evaluative research is practical and efficient.

Asia↗
PubMed2001

Feasibility and initial results of an Internet-based pacemaker and ICD pulse generator and lead registry.

The medical community has no independent source of timely information regarding the performance of pacemaker and ICD pulse generators and leads. Accordingly, the authors established an Internet-based registry of pacemaker and ICD pulse generator and lead failures (www.pacerandicregistry.com). During the first year, they found three previously unreported device problems that were promptly communicated to the participants. Of the failures reported, 11% of ICD and 10% of pacemaker pulse generator failures were heralded by signs other than the expected elective replacement indicator (ERI). Average ICD battery longevity was 4.0 +/- 0.7 years, and average dual chamber pacemaker battery longevity was 6.8 +/- 2.6 years. Disrupted insulation accounted for 54% of pacemaker and 29% of ICD lead failures. Compared to pacemaker pulse generator and lead failure, ICD device failures were more likely to cause severe clinical consequences. In conclusion, an Internet-based registry is feasible and capable of providing timely data regarding the signs, causes, and clinical consequences of pacemaker and ICD failures.

Canada↗
PubMed2001

Providing hospice care in rural Texas.

Hospice organizations in rural areas face many logistical and financial challenges. The authors review their experiences in offering hospice care to a widely dispersed population of patients. Crown of Texas Hospice, headquartered in Amarillo, Texas, provides hospice care throughout most of the vast and sparsely populated Texas panhandle. In the United States, patients typically are not referred to hospice care until the very end of the terminal phase of their disease process. Late referrals limit the opportunities for optimal symptom management and also limit the ability of a hospice organization to meet the psychosocial and spiritual needs of patients and their families. Recommendations to improve the timeliness of hospice referral are suggested.

Aged↗
PubMed2000

Oncogenes induce and activate endogenous p73 protein.

The identification of upstream pathways that signal to TP73 is crucial for understanding the biological role of this gene. Since some evidence suggests that TP73 might play a role in tumorigenesis, we asked whether oncogenes can induce and activate endogenous TP73. Here, we show that endogenous p73 alpha and beta proteins are up-regulated in p53-deficient tumor cells in response to overexpressed E2F1, c-Myc, and E1A. E2F1, c-Myc, and E1A-mediated p73 up-regulation leads to activation of the p73 transcription function, as shown by p73-responsive reporter activity and by induction of known endogenous p73 target gene products such as p21 and HDM2. Importantly, E2F1-, c-Myc-, and E1A-mediated activation of endogenous p73 induces apoptosis in SaOs-2 cells. Conversely, inactivation of p73 by a dominant negative p73 inhibitor (p73DD), but not by a mutant p73DD, inhibits oncogene-induced apoptosis. These data show that oncogenes can signal to TP73 in vivo. Moreover, in the absence of p53, oncogenes may enlist p73 to induce apoptosis in tumor cells.

Adenovirus E1A Proteins↗
PubMed2000

A common E2F-1 and p73 pathway mediates cell death induced by TCR activation.

Strong stimulation of the T-cell receptor (TCR) on cycling peripheral T cells causes their apoptosis by a process called TCR-activation-induced cell death (TCR-AICD). TCR-AICD occurs from a late G1 phase cell-cycle check point independently of the 'tumour suppressor' protein p53. Disruption of the gene for the E2F-1 transcription factor, an inducer of apoptosis, causes significant increases in T-cell number and splenomegaly. Here we show that T cells undergoing TCR-AICD induce the p53-related gene p73, another mediator of apoptosis, which is hypermethylated in lymphomas. Introducing a dominant-negative E2F-1 protein or a dominant-negative p73 protein into T cells protects them from TCR-mediated apoptosis, whereas dominant-negative E2F-2, E2F-4 or p53 does not. Furthermore, E2F-1-null or p73-null primary T cells do not undergo TCR-mediated apoptosis either. We conclude that TCR-AICD occurs from a late G1 cell-cycle checkpoint that is dependent on both E2F-1 and p73 activities. These observations indicate that, unlike p53, p73 serves to integrate receptor-mediated apoptotic stimuli.

Animals↗
PubMed2000

Role for the p53 homologue p73 in E2F-1-induced apoptosis.

The transcription factor E2F-1 induces both cell-cycle progression and, in certain settings, apoptosis. E2F-1 uses both p53-dependent and p53-independent pathways to kill cells. The p53-dependent pathway involves the induction by E2F-1 of the human tumour-suppressor protein p14ARF, which neutralizes HDM2 (human homologue of MDM2) and thereby stabilizes the p53 protein. Here we show that E2F-1 induces the transcription of the p53 homologue p73. Disruption of p73 function inhibited E2F-1-induced apoptosis in p53-defective tumour cells and in p53-/- mouse embryo fibroblasts. We conclude that activation of p73 provides a means for E2F-1 to induce death in the absence of p53.

Animals↗
PubMed2000

Discovery of High Proper-Motion Ancient White Dwarfs: Nearby Massive Compact Halo Objects?

We present the discovery and spectroscopic identification of two very high proper-motion ancient white dwarf stars, found in a systematic proper-motion survey. Their kinematics and apparent magnitude clearly indicate that they are halo members, while their optical spectra are almost identical to the recently identified cool halo white dwarf WD 0346+246. Canonical stellar halo models predict a white dwarf volume density that is 2 orders of magnitude less than the rho approximately 7x10-4 M middle dot in circle pc-3 inferred from this survey. With the caveat that the sample size is very small, it appears that a significant fraction, approximately 10%, of the local dark matter halo is in the form of very old, cool, white dwarfs.

Journal Article↗
PubMed2000

Granulocyte-macrophage colony-stimulating factor priming plus papillomavirus E6 DNA vaccination: effects on papilloma formation and regression in the cottontail rabbit papillomavirus--rabbit model.

A cottontail rabbit papillomavirus (CRPV) E6 DNA vaccine that induces significant protection against CRPV challenge was used in a superior vaccination regimen in which the cutaneous sites of vaccination were primed with an expression vector encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine that induces differentiation and local recruitment of professional antigen-presenting cells. This treatment induced a massive influx of major histocompatibility complex class II-positive cells. In a vaccination-challenge experiment, rabbit groups were treated by E6 DNA vaccination, GM-CSF DNA inoculation, or a combination of both treatments. After two immunizations, rabbits were challenged with CRPV at low, moderate, and high stringencies and monitored for papilloma formation. As expected, all clinical outcomes were monotonically related to the stringency of the viral challenge. The results demonstrate that GM-CSF priming greatly augmented the effects of CRPV E6 vaccination. First, challenge sites in control rabbits (at the moderate challenge stringency) had a 0% probability of remaining disease free, versus a 50% probability in E6-vaccinated rabbits, and whereas GM-CSF alone had no effect, the interaction between GM-CSF priming and E6 vaccination increased disease-free survival to 67%. Second, the incubation period before papilloma onset was lengthened by E6 DNA vaccination alone or to some extent by GM-CSF DNA inoculation alone, and the combination of treatments induced additive effects. Third, the rate of papilloma growth was reduced by E6 vaccination and, to a lesser extent, by GM-CSF treatment. In addition, the interaction between the E6 and GM-CSF treatments was synergistic and yielded more than a 99% reduction in papilloma volume. Finally, regression occurred among the papillomas that formed in rabbits treated with the E6 vaccine and/or with GM-CSF, with the highest regression frequency occurring in rabbits that received the combination treatment.

Animals↗
PubMed2000

Living wills.

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Health Care Rationing↗
PubMed2000

Effects of sleep and sleep deprivation on interleukin-6, growth hormone, cortisol, and melatonin levels in humans.

The objective of this study was to evaluate the effects of nocturnal sleep, partial night sleep deprivation, and sleep stages on circulating concentrations of interleukin-6 (IL-6) in relation to the secretory profiles of GH, cortisol, and melatonin. In 31 healthy male volunteers, blood samples were obtained every 30 min during 2 nights: uninterrupted, baseline sleep and partial sleep deprivation-early night (awake until 0300 h). Sleep was measured by electroencephalogram polysomnography. Sleep onset was associated with an increase in serum levels of IL-6 (P < 0.05) during baseline sleep. During PSD-E, the nocturnal increase in IL-6 was delayed until sleep at 0300 h. Sleep stage analyses indicated that the nocturnal increase in IL-6 occurred in association with stage 1-2 sleep and rapid eye movement sleep, but levels during slow wave sleep were not different from those while awake. The profile of GH across the 2 nights was similar to that of IL-6, whereas the circadian-driven hormones cortisol and melatonin showed no concordance with sleep. Loss of sleep may serve to decrease nocturnal IL-6 levels, with effects on the integrity of immune system functioning. Alternatively, given the association between sleep stages and IL-6 levels, depressed or aged populations who show increased amounts of REM sleep and a relative loss of slow wave sleep may have elevated nocturnal concentrations of IL-6 with implications for inflammatory disease risk.

Adult↗