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Biomedical subjects

L O'Neill

Publications and source records attributed to L O'Neill.

At least 37 records · Page 2Linked to original sources
PubMed2000

Surgeon characteristics associated with mortality and morbidity following carotid endarterectomy.

PURPOSE: To identify surgeon characteristics associated with mortality or morbidity, following carotid endarterectomy (CEA). METHODS: Data on all inpatient discharges from the 284 nonfederal Pennsylvania hospitals were obtained from the Pennsylvania Health Care Cost Containment Council for the period from 1994 to 1995. Physician data were obtained from the Physicians List of the American Medical Association, including name, gender, specialty, year of birth, board certified, and year of licensure. Cases were selected if any of six procedures codes were ICD-9-CM rubric 38.12, indicating CEA. RESULTS: Among the 12,725 cases studied, in-hospital mortality was 0.7%, nonfatal morbidity was 3.0%, and the total bad outcome rate was 3.7%. Surgeons who performed 1 to 2 CEAs over 2 years had the highest mortality (2.0%) and total bad outcome (9.2%) rates. For surgeons performing three or more cases in 2 years, increased volume was not associated with better outcomes. A greater number of years since the surgeon was licensed was associated with greater mortality (p = 0.001), but not with morbidity or bad outcome rates. In regression analyses that adjusted for patient risk, both years since licensure and specialty predicted surgical mortality rate, but only volume predicted surgical bad outcome rate. CONCLUSIONS: More years since licensure and very low patient volume are associated with worse patient outcomes following CEA.

Adult↗
PubMed2000

Energy balance, viral burden, insulin-like growth factor-1, interleukin-6 and growth impairment in children infected with human immunodeficiency virus.

OBJECTIVE: To determine the relationship between energy metabolism and growth abnormalities in HIV-infected children and to assess clinical or laboratory characteristics which may be contributing factors to their growth impairment. DESIGN: A comparative study. METHODS: We measured energy intake by inpatient calorie count/outpatient 24 h food recalls, resting energy expenditure by indirect calorimetry, total energy expenditure by the doubly-labeled water technique, iron metabolism, protein metabolism, and lipid metabolism markers as well as CD4 count, viral load, insulin-like growth factor-1 (IGF-1), serum interleukin-6 (IL-6), and whole blood stimulated IL-6 levels in prepubertal congenitally HIV-infected children with normal and impaired growth patterns. RESULTS AND CONCLUSIONS: Differences in energy expenditures were not found between normal and growth-impaired HIV-infected children. Energy intake but not energy expenditure was significantly reduced when HIV-infected children were compared to expected normal values for age and gender. Advanced HIV clinical disease, severe immune suppression, increased viral burden, increased IL-6 activity, decreased total serum protein, and decreased IGF-1 levels were more likely to be found in HIV-infected children with growth impairment in comparison with HIV-infected children with normal growth.

Adolescent↗
PubMed2000

Change in cervical length after cerclage as a predictor of preterm delivery.

OBJECTIVE: To determine whether the degree of cervical lengthening after cerclage and whether serial follow-up measurements of cervical length after cerclage are predictive of pregnancy outcome. METHODS: Eighty women whose primary physician determined that a prophylactic (n = 50) or urgent cerclage (n = 30) was indicated had transvaginal ultrasonographic evaluation before and after cerclage. Thereafter, most women had three additional transvaginal ultrasound examinations until 32 weeks' gestation. At each examination, the mean of three measurements was calculated. Statistical analyses were done by t test, analysis of variance, and logistic regression, with significance set at P <.05. RESULTS: The mean +/- standard deviation precerclage cervical length was 27.2 +/- 10.3 mm and after cerclage was 34.1 +/- 9.9 mm (n = 80, P <.001, paired t test). No significant association was found (r = -0.26) between the difference in cervical length (postcerclage - precerclage lengths) and pregnancy outcome. Patients with a prophylactic cerclage had a mean cervical length that was consistently longer in patients delivering at term compared with those who delivered preterm at 20 to 32 weeks' gestation. In the urgent cerclage group a significant difference in cervical length between those who delivered at term compared with preterm was evident only at 28 to 32 weeks. CONCLUSION: The increase in cervical length after cerclage is not predictive of term delivery. Serial cervical length measurements in the late second or early third trimester predict preterm birth but could provide earlier warning in patients with a prophylactic cerclage than in patients with urgent cerclage.

Adult↗
PubMed2000

The Toll/interleukin-1 receptor domain: a molecular switch for inflammation and host defence.

The pro-inflammatory cytokine interleukin-1 (IL-1) signals via the Type-I IL-1 receptor (IL-1RI), inducing an increase in the expression of many genes with roles in immunity and inflammation. The signalling pathways involve two adapter proteins, MyD88 and Tollip, which via two IL-1 receptor-associated kinases (IRAK and IRAK-2) activate transcription factors such as nuclear factor-kappa B and protein kinases such as p38 mitogen-activated protein kinase. A role for the low-molecular-mass G-proteins Rac, Ras and Rap in these processes has also been indicated. IL-1RI is the founder of a diverse superfamily of receptors, which all share a cytosolic domain, termed the Toll/IL-1 receptor (TIR) domain. The superfamily can be divided broadly into three subgroups. The first of these is most similar to IL-1RI and includes the receptor for IL-18 and the Th2 cell regulator T1/ST2. The second subgroup is most similar to the Drosophila melanagaster protein Toll and includes Toll-like receptor 2 (TLR2), which is required for host defence against Gram-positive bacteria and fungi, and TLR4, which is required for lipopolysaccharide responsiveness, and thus is involved in host defence against Gram-negative bacteria. There are also a number of TLRs in plants and insects, all involved in host defence. The third subgroup contains non-receptor proteins which possess a TIR domain and are cytosolic. MyD88 is a member, and it presumably complexes with IL-1RI via a TIR-TIR interaction. The other two members are proteins encoded by the vaccinia virus, A46R and A52R, which block TIR-dependent signalling. This receptor superfamily therefore appears to play a central role in inflammation and host defence against infection, pointing to the TIR domain as a critical molecular player in the innate immune response.

Animals↗
PubMed2000

Activated protein C inhibits lipopolysaccharide-induced nuclear translocation of nuclear factor kappaB (NF-kappaB) and tumour necrosis factor alpha (TNF-alpha) production in the THP-1 monocytic cell line.

Activated protein C (APC) protects against sepsis in animal models and inhibits the lipopolysacharide (LPS)-induced elaboration of proinflammatory cytokines from monocytes. The molecular mechanism responsible for this property is unknown. We assessed the effect of APC on LPS-induced tumour necrosis factor alpha (TNF-alpha) production and on the activation of the central proinflammatory transcription factor nuclear factor-kappaB (NF-kappaB) in a THP-1 cell line. Cells were preincubated with varying concentrations of APC (200 microg/ml, 100 microg/ml and 20 microg/ml) before addition of LPS (100 ng/ml and 10 microg/ml). APC inhibited LPS-induced production of TNF-alpha both in the presence and absence of fetal calf serum (FCS), although the effect was less marked with 10% FCS. APC also inhibited LPS-induced activation of NF-kappaB, with APC (200 microg/ml) abolishing the effect of LPS (100 ng/ml). The ability of APC to inhibit LPS-induced translocation of NF-kappaB is likely to be a significant event given the critical role of the latter in the host inflammatory response.

Analysis of Variance↗
PubMed2000

Complications of treatment with local field external beam radiotherapy for localized prostate cancer.

We performed this analysis to document the rate and severity of complications both during and after local field irradiation for localized prostate cancer and to assess the influence of three-dimensional conformal radiation therapy (3DCRT) on these complications. Bowel, urinary and cutaneous toxicities were noted in all patients treated with primary radiotherapy (RT) for prostate cancer using Radiation Therapy Oncology Group/European Organization for Research on Treatment of Cancer scores. Evaluations were performed weekly during RT, 6 weeks after RT and 3 monthly thereafter. Data on 111 were analysed. We also compared the complications of conventional and 3DCRT. The serious complication rates identified in this study compare favourably with those reported in the literature. Only 3.6%, 0.8% and 0% had acute grade 3 or 4 urinary, bowel or skin reactions respectively. Only two patients had chronic grade 3 or 4 urinary complications. Thus far no patients have developed chronic bowel or skin complications greater than grade 2. Despite dose escalation from 66 Gy to 70 Gy (with 3DCRT), there was a trend towards reduced toxicity when 3DCRT was compared with conventional radiation. RT is a well-tolerated treatment for early stage carcinoma of the prostate and our complication rates are compatible with international experiences. Further follow-up is required to determine the efficacy of treatment, the incidence of impotence and the final number of late complications.

Adenocarcinoma↗
PubMed2000

Scheduling surgical cases into overflow block time- computer simulation of the effects of scheduling strategies on operating room labor costs.

UNLABELLED: "Overflow" block time is operating room (OR) time for a surgical group's cases that cannot be completed in the regular block time allocated to each surgeon in the surgical group. Having such overflow block time increases OR utilization. The optimal way to schedule patients into a surgical group's overflow block time is unknown. In this study, we developed a scheduling strategy that balances the OR manager's need to reduce staffing costs and the needs of patients and surgeons for flexibility in choosing the dates and times of cases. We used computer simulation to evaluate our scheduling strategy. Surgeons and patients (i) can schedule the case into any overflow block within 2 wk; (ii) can only schedule the case into a "first case of the day" start time more than 2 wk in the future if there is not enough open time for the case within 2 wk; (iii) must schedule the case to be done within 4 wk; and (iv) are encouraged to perform the case on the earliest possible date. Staffing costs were lowest when the OR manager did not incorporate surgeon and patient preferences when scheduling cases into overflow block time. The strategy we developed provides surgeons and patients with some flexibility in scheduling, while only increasing OR staffing costs slightly over the minimum achieved when the OR manager controls scheduling. IMPLICATIONS: The strategy we developed provides surgeons and patients with some flexibility in scheduling, while increasing OR staffing costs only slightly over the minimum achieved when the OR manager controls scheduling. Staffing costs were lowest when the operating room (OR) manager did not incorporate surgeon and patient preferences when scheduling cases into overflow block time.

Appointments and Schedules↗
PubMed2000

On the need for monitor unit calculations as part of a beam commissioning methodology for a radiation treatment planning system.

This paper illustrates the need for validating the calculation of monitor units as part of the process of commissioning a photon beam model in a radiation treatment planning system. Examples are provided in which this validation identified subtle errors, either in the dose model or in the implementation of the dose algorithm. These errors would not have been detected if the commissioning process only compared relative dose distributions. A set of beam configurations, with varying field sizes, source-to-skin distances, wedges, and blocking, were established to validate monitor unit calculations for two different beam models in two different radiation treatment planning systems. Monitor units calculated using the treatment planning systems were compared with monitor units calculated from point dose calculations from tissue-maximum ratio (TMR) tables. When discrepancies occurred, the dose models and the code were analyzed to identify the causes of the discrepancies. Discrepancies in monitor unit calculations were both significant (up to 5%) and systematic. Analysis of the dose computation software found: (1) a coordinate system transformation error, (2) mishandling of dose-spread arrays, (3) differences between dose calculations in the commissioning software and the planning software, and (4) shortcomings in modeling of head scatter. Corrections were made in the beam calculation software or in the data sets to overcome these discrepancies. Consequently, we recommend incorporating validation of monitor unit calculations as part of a photon beam commissioning process.

Algorithms↗
PubMed1999

Interleukin-1 receptor-associated kinase and TRAF-6 mediate the transcriptional regulation of interleukin-2 by interleukin-1 via NFkappaB but unlike interleukin-1 are unable to stabilise interleukin-2 mRNA.

Interleukin-1 receptor-associated kinase, IRAK, has been shown to activate NFkappaB in response to interleukin-1. We have explored the involvement of IRAK in regulation of the interleukin-2 gene in the murine thymoma cell line EL4.NOB-1 by examining its effect on interleukin-2 promoter-linked reporter gene expression, interleukin-2 gene transcription and interleukin-2 protein production. Cells transfected with IRAK displayed high levels of phosphorylated IRAK, increased interleukin-2 promoter-linked reporter gene expression (which was dependent on NFkappaB) and interleukin-2 gene transcription. IRAK was unable, however, to increase interleukin-2 protein production. Overexpression of TRAF-6 induced similar responses and again failed to increase interleukin-2 protein production. A dominant negative TRAF-6 inhibited reporter gene expression and interleukin-2 protein production in response to both interleukin-1 and IRAK transfection. Interleukin-1 treatment and IRAK or TRAF-6 transfection increased interleukin-2 mRNA production. Only interleukin-1 treatment stabilised the induced transcripts with 50% being detectable at 20 h post induction. The interleukin-2 mRNA induced in IRAK- or TRAF-6-transfected cells was depleted by >90% at 6 h post induction. These data implicate IRAK and TRAF-6 in transcriptional regulation of interleukin-2 gene expression via NFkappaB, and provide direct evidence that IRAK lies upstream from TRAF-6. Neither IRAK nor TRAF-6 participates in stabilisation of interleukin-2 mRNA which is required for interleukin-2 protein production.

Animals↗
PubMed1999

Change in cervical length after prophylactic cerclage.

OBJECTIVE: To determine changes in length of incompetent cervices after cerclage, using transvaginal ultrasound. METHODS: Patients were enrolled in a prospective, observational study under an Institutional Review Board-approved protocol. McDonald or Shirodkar sutures were placed according to physician preference. Pre- and postcerclage cervical lengths were measured within 72 hours of the procedure. At each examination, the first measurement was discarded, and a mean of the subsequent three measurements was calculated. RESULTS: Twenty-one Shirodkar and ten McDonald operations were done. The mean (+/- standard deviation) precerclage cervical length was 2.7+/-0.9 cm and the postcerclage cervical length was 3.6+/-0.9 cm (P<.001, paired t test). CONCLUSION: Prophylactic cerclage results in measurable increases in cervical length, which might contribute to the success of the procedure. Further study is needed to determine whether the degree of cervical lengthening after cerclage predicts term delivery.

Adult↗
PubMed1999

Myocardial retinoid X receptor, thyroid hormone receptor, and myosin heavy chain gene expression in the rat during adult aging.

Although previous studies have shown that cardiac myosin heavy chain (MHC) composition undergoes a switch from the alpha- to beta-isoform in the heart during adult aging, the underlying mechanisms responsible for this switch are unknown. Cardiac MHC gene expression is regulated, in part, by thyroid hormone responsive elements present in the regulatory control regions of the alpha- and beta-MHC genes. Age-associated changes in the expression of thyroid hormone receptors (THRs) and/or retinoid X receptors (RXRs), the heterodimeric partner for THRs, could explain the age-associated changes in MHC expression. Accordingly, we measured mRNA levels for the cardiac muscle MHCs and the rat THR and RXR genes in the left ventricles of Wistar rats at 2, 6, and 24 months of age. Although there were no significant changes in RXR alpha or RXR beta mRNA levels with age, both alpha 1 and alpha 2 THR mRNA levels decreased significantly between 2 and 6 months of age. During this same time period, the mRNA levels for alpha-MHC declined by more than half, whereas beta-MHC mRNA levels remained low and unchanged. On the other hand, between 6 and 24 months, when mRNA levels for beta-MHC increased and alpha-MHC continued to decrease, there was a significant decline in THR beta 1 and RXR gamma mRNA levels accompanied by a reduction in the THR beta 1 and RXR gamma protein levels. These data show a pattern of change that suggests that the decline in alpha-MHC gene expression may be biphasic and due to a decline in alpha 1 (and possibly alpha 2) THR levels between 2 and 6 months of age and a decline in THR beta 1 and RXR gamma levels at later stages. In contrast, the increase in beta-MHC gene expression was associated only with the changes in THR beta 1 and RXR gamma mRNA and protein levels.

Aging↗
PubMed1999

A strategy for deciding operating room assignments for second-shift anesthetists.

UNLABELLED: We developed a relief strategy for assigning second-shift anesthetists to late-running operating rooms. The strategy relies on a statistical method which analyzes historical case durations available from surgical services information systems to estimate the expected (mean) remaining hours in cases after they have begun. We tested our relief strategy by comparing the number of hours that first-shift anesthetists would work overtime if second-shift anesthetists were assigned using our strategy versus if the anesthesia coordinator knew in advance the exact amount of time remaining in each case. Our relief strategy resulted in 3.4% to 4.9% more overtime hours for first-shift anesthetists than the theoretical minimum, as would have been obtained had perfect retrospective knowledge been available. Few additional staff hours would have been saved by supplementing our relief strategy with other methods to monitor case durations (e.g., real-time patient tracking systems or closed circuit cameras in operating rooms). IMPLICATIONS: A relief strategy that relies only on analyzing historical case durations from an operating room information system to predict the time remaining in cases performs well at minimizing anesthetist staffing costs.

Algorithms↗
PubMed1998

Enhanced expression of p53 and apoptosis induced by blockade of the vacuolar proton ATPase in cardiomyocytes.

Activation of the vacuolar proton ATPase (VPATPase) has been implicated in the prevention of apoptosis in neutrophils and adult cardiac myocytes. To determine the role of the VPATPase in apoptosis of cardiac myocytes, we used a potent and specific inhibitor of the VPATPase, bafilomycin A1. Bafilomycin A1 alone caused increased DNA laddering of genomic DNA and increased nuclear staining for fragmented DNA in neonatal cardiomyocyte apoptosis in a dose- and time-dependent manner. Intracellular acidification in cardiac myocytes was also observed after 18 h of bafilomycin A1 treatment. Accordingly, bafilomycin A1-treated myocytes also showed increased accumulation of p53 protein and p53-dependent transactivation of gene expression, including a persistent upregulation of p21/wild-type p53 activated fragment 1/cyclin kinase inhibitor protein-1 mRNA. The bafilomycin A1-induced increase in p53 protein levels was accompanied by a marked increase in p53 mRNA accumulation. In contrast, cardiac fibroblasts treated with bafilomycin A1 showed no change in p53 protein expression or pHi and did not undergo apoptosis even after 24 h of treatment. Our data suggest that blockade of the VPATPase induces apoptotic cell death of cardiac myocytes and that this may occur through a p53-mediated apoptotic pathway.

Animals↗
PubMed1998

Stimulation of P2Y receptors activates c-fos gene expression and inhibits DNA synthesis in cultured cardiac fibroblasts.

OBJECTIVES: The aims of this study were to determine (1) whether neonatal rat cardiac fibroblasts (CAFB) express P2Y receptors; (2) whether CAFB respond to extracellular ATP by inducing expression of c-fos mRNA; and (3) whether extracellular ATP modulates norepinephrine (NE)-stimulated cell growth in CAFB. METHODS: Expression of P2Y1 and P2Y2 receptors and induction of c-fos were examined by Northern blot analysis. CAFB growth was assessed by measuring [3H]thymidine incorporation and DNA content. P2Y receptor pharmacology was studied using various ATP analogues. RESULTS: Northern blot analysis of polyA enriched RNA confirmed that at least 2 subtypes of P2Y receptors (P2Y1 and P2Y2) are expressed in cultured CAFB. Extracellular ATP induced the expression of c-fos mRNA through a pathway that was sensitive to inhibitors of protein kinase C (PKC), but not to inhibitors of intracellular Ca2+ signaling. Extracellular ATP inhibited the NE-stimulated increases in DNA content and in [3H]thymidine incorporation into DNA. Whereas the potency order for stimulation of c-fos expression was ATP = UTP > ADP > adenosine, the potency order to inhibit the NE-induced increase of [3H]thymidine incorporation into DNA was ATP > ADP > UTP > adenosine. CONCLUSIONS: These data demonstrate that CAFB express both P2Y1 and P2Y2 receptor mRNA and that CAFB respond to P2Y receptor stimulation by induction of c-fos and inhibition of DNA synthesis. These findings suggest that the effects of ATP on [3H]thymidine incorporation into DNA and on expression of c-fos mRNA are exerted via distinct P2Y receptor subtypes.

Adenosine Triphosphate↗
PubMed1998

Multifactor efficiency in data envelopment analysis with an application to urban hospitals.

A perennial difficulty in measuring hospital efficiency, and one with important policy implications, is how to compare teaching versus non-teaching hospitals. This problem reflects a broader methodological concern in Data Envelopment Analysis (DEA), which is the comparison of specialist and non-specialist Decision-Making Units (DMUs). This paper presents a new performance measure in DEA, termed multifactor efficiency, which represents an average partial factor productivity index summed over all output-input ratios. We apply this technique to measure the performance of 27 large, urban hospitals, including 13 teaching hospitals. These results were reviewed and validated by a panel of health care experts, and multifactor efficiency was shown to offer several benefits that enhance and complement existing performance measures in DEA.

Decision Making, Organizational↗
PubMed1997

p53 and the hypoxia-induced apoptosis of cultured neonatal rat cardiac myocytes.

Myocyte cell loss is a prominent and important pathogenic feature of cardiac ischemia. We have used cultured neonatal rat cardiac myocytes exposed to prolonged hypoxia as an experimental system to identify critical factors involved in cardiomyocyte death. Exposure of myocytes to hypoxia for 48 h resulted in intranucleosomal cleavage of genomic DNA characteristic of apoptosis and was accompanied by increased p53 transactivating activity and protein accumulation. Expression of p21/WAF-1/CIP-1, a well-characterized target of p53 transactivation, also increased in response to hypoxia. Hypoxia did not cause DNA laddering or cell loss in cardiac fibroblasts. To determine whether the increase in p53 expression in myocytes was sufficient to induce apoptosis, normoxic cultures were infected with a replication-defective adenovirus expressing wild-type human p53 (AdCMV.p53). Infected cells expressed high intracellular levels of p53 protein and exhibited the morphological changes and genomic DNA fragmentation characteristic of apoptosis. In contrast, no genomic DNA fragmentation was observed in myocytes infected with the control virus lacking an insert (AdCMV.null) or in cardiac fibroblasts infected with AdCMV.p53. These results suggest that the intracellular signaling pathways activated by p53 might play a critical role in the regulation of hypoxia-induced apoptosis of cardiomyocytes.

Animals↗
PubMed1997

Clinical significance of antinuclear antibodies: comparison of detection with immunofluorescence and enzyme-linked immunosorbent assays.

OBJECTIVE: To compare the measurement of antinuclear antibodies (ANA) by immunofluorescence and by 6 different commercial enzyme-linked immunosorbent assays (ELISAs) in clearly defined patient groups and serum samples. METHODS: Serum samples were derived from 3 sources: 1) patients with a known clinical diagnosis of systemic lupus erythematosus (SLE) (group 1), 2) sera with known monospecific ANA reactivity (group 2), and 3) sera from consecutive patients for whom ANA testing had been ordered (group 3). Each of these sera was tested for the presence of ANA by immunofluorescence on HEp-2 cells, and by using each of 6 commercially available ELISA ANA kits. RESULTS: In patients with known clinical SLE, 88% were ANA positive by immunofluorescence. Positivity with the different ELISAs ranged from 62% to 90%. While most ELISAs successfully detected antibodies to SS-A, RNP, and Sm, there were significant differences between assays in the detection of anticentromere antibodies and anti-DNA. Measurement of ANA in consecutive patients for whom an ANA test was requested showed that, generally, those assays with high sensitivity for detection of SLE had a high false-positive rate, whereas those assays with a low false-positive rate failed to identify some patients with a clinical diagnosis of SLE. CONCLUSION: There are significant differences in the detection of ANA by immunofluorescence and different ELISA kits. Agreement between different assays is generally marginal. When ordering and interpreting an ANA test, the clinician must be familiar with the specific assay being used to measure ANA and the differences between the various ANA assays.

Antibodies, Antinuclear↗