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Biomedical subjects

K O'Neill

Publications and source records attributed to K O'Neill.

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

Incidence and susceptibility of pathogenic bacteria vary between intensive care units within a single hospital: implications for empiric antibiotic strategies.

BACKGROUND: The purpose of this study was to determine whether the incidence of recovery and patterns of antibiotic susceptibility of pathogenic bacteria vary between intensive care units (ICUs) in a single teaching hospital. METHODS: Culture and susceptibility results were collected prospectively for a 3-month period (April through June 1999) in each of the surgical, trauma, and medical ICUs. The number of unique isolates and susceptibility patterns were determined. Susceptibility of isolates among ICUs was compared with chi2. RESULTS: Statistically significant differences between ICUs in susceptibility to various antibiotics were found for Staphylococcus aureus, Enterococcus sp, Acinetobacter sp, Enterobacter sp, Klebsiella sp, and Pseudomonas sp. Notably, vancomycin-resistant Enterococcus was not seen in the medical ICU, whereas it was seen in both the surgical and trauma ICUs. Klebsiella spp resistant to ceftazidime were seen only in the trauma ICU. The aminoglycosides and quinolones had attenuated activity against Pseudomonas sp in the surgical ICU, whereas they remained highly effective in the trauma ICU. Cefazolin had no activity against the Enterobacter sp in either of the surgical ICUs, but was highly effective in the medical ICU. CONCLUSION: Although the microbiologic results of this study should not be extrapolated to other institutions, the principle is of value. There is variability between ICUs in a single large teaching hospital in susceptibility of bacterial pathogens to various antibiotics. This may have implications in the design of empiric antibiotic strategies and the planning of the hospital formulary. Hospital wide or composite ICU antibiograms are inadequate for planning empiric therapy in the ICU.

Antibiotic Prophylaxis↗
PubMed2000

Hyphomonas adhaerens sp. nov., Hyphomonas johnsonii sp. nov. and Hyphomonas rosenbergii sp. nov., marine budding and prosthecate bacteria.

Three strains of prosthecate, budding bacteria, MHS-2T, MHS-3T and VP6T, were isolated from marine habitats including the open ocean (the pelagic zone), the offshore region (the neritic zone) and the hydrothermal vent region. A polyphasic approach including 16S rDNA sequencing, phenotypic analyses, serology, fatty acid analyses, membrane protein profiles and DNA-DNA hybridizations was used to place these strains in the genus Hyphomonas, a taxon of the alpha-Proteobacteria. The results of these analyses also showed that strains MHS-3T, MHS-2T and VP6T each represent a new species of Hyphomonas. The names Hyphomonas adhaerens (type strain MHS-3T, ATCC 43965T), Hyphomonas johnsonii (type strain MHS-2T, ATCC 43964T) and Hyphomonas rosenbergii (type strain VP6T, ATCC 43869T) are proposed for the new species. With these additions, Hyphomonas now contains eight species.

Alphaproteobacteria↗
PubMed2000

The melanin-concentrating hormone receptor couples to multiple G proteins to activate diverse intracellular signaling pathways.

The receptor for melanin-concentrating hormone (MCH) was recently identified as the orphan G protein-coupled receptor SLC-1. In this study, a CHO cell line expressing the MCH receptor (Kd = 1.3 nM; binding capacity, 3.6 pmol/mg protein) is used to assess the ability of the MCH receptor to couple to Gi, Go, and Gq proteins. The results demonstrate that MCH inhibits forskolin-stimulated cAMP production in a pertussis toxin- (PTX)-sensitive manner in CHO-MCHR cells (EC50 = 100 pM), indicating that the MCH receptor couples to one or more members of the Gi subfamily of G proteins. In addition, MCH stimulates increases in phosphoinositide metabolism (EC50 = 50 nM) and in intracellular free Ca2+ levels (EC50 = 10 nM). MCH-stimulated inositol phosphate production and increases in intracellular free Ca2+ are partially inhibited (60% and 40%, respectively) by PTX pretreatment, demonstrating that there are at least two components of each of these signaling pathways. One component is PTX sensitive and therefore mediated through a Gi/Go protein. A distinct G protein-coupled (probably Gq type) mediates the PTX-insensitive component. To distinguish Gi vs. Go coupling, MCH-stimulated mitogen-activated protein (MAP) kinase activity was examined. Gi and Go use separate signaling pathways to mediate MAP kinase activation in CHOcells. Protein kinase C (PKC) activity is essential in the Go-dependent MAP kinase signaling pathway, but is not required in the GC-dependent MAP kinase signaling pathway. MCH stimulated MAP kinase activity is decreased (50%), but not abolished, by inhibition of PKC activity or depletion of cellular PKC, indicating that MCH-stimulated MAP kinase activity is mediated through both Gi- and Go-dependent signaling mechanisms. The results of this study are the first to clearly demonstrate that the MCH receptor couples to multiple G proteins to mediate several diverse intracellular signaling pathways.

Adenylyl Cyclases↗
PubMed1999

Capillary electrophoresis using diol-bonded fused-silica capillaries.

In this paper, 3-glycidoxypropyltrimethoxysilane was used to produce diol-bonded capillaries at room temperature for capillary electrophoresis (CE). A variety of standard reference compounds and authentic biological samples including ribonucleotides, peptides and proteins were used to test the columns. It was found that greatly suppressed electroosmotic flow was measured over a pH range of 3-10. Lower than 1.6% relative standard deviation (> 10 runs) in migration time was observed for the analysis of test proteins. For real samples of ribonucleotides in tumor cell extracts, approximately 1 million theoretical plates and excellent peak shapes were obtained. The high column efficiency and symmetrical peaks allowed the separation of samples with only 0.6% maximum difference in migration times. The diol-bonded fused-silica capillary columns were stable when used in a pH range of 2-8 under typical CE conditions. The column preparation method involved a simple dynamic coating procedure at room temperature, greatly simplifying the more typical static coating methods that require vacuum pumps and ovens.

Amino Acid Sequence↗
PubMed1999

Clinical pharmacokinetics of the CD19 receptor-directed tyrosine kinase inhibitor B43-Genistein in patients with B-lineage lymphoid malignancies.

The authors examined the pharmacokinetics of the CD19 receptor-directed tyrosine kinase inhibitor B43-Genistein in 17 patients (4 children, 13 adults) with B-lineage lymphoid malignancies, including 12 patients with acute lymphoblastic leukemia (ALL) and 5 patients with non-Hodgkin's lymphoma (NHL). The immunoconjugate was administered intravenously as a 1-hour continuous infusion at a dose level of either 0.1 mg/kg (N = 12) or 0.18 mg/kg (N = 5), and the plasma concentration-time data were modeled by using the WinNonlin program to estimate the pharmacokinetic parameters. Pharmacokinetic analyses revealed a plasma half-life of 19 +/- 4 hours, mean residence time of 22 +/- 4 hours, and a systemic clearance of 18 +/- 2 mL/h/kg. The average (mean +/- SEM) values for the maximum plasma concentration Cmax, volume of distribution at steady state (Vss), and area under curve (AUC) were 1092 +/- 225 ng/ml, 291 +/- 37 mL/kg, and 9987 +/- 2021 micrograms x h/L, respectively. The AUC values were higher at the 0.18 mg/kg dose level than at the 0.1 mg/kg dose level (16,848 +/- 5118 micrograms x h/L vs. 7128 +/- 1156 micrograms x h/L, p = 0.009). Patients with ALL had a significantly larger volume of distribution at steady state (332 +/- 47 mL/kg vs. 191 +/- 12 mL/kg, p = 0.04), faster clearance (21 +/- 3 mL/h/kg vs. 11 +/- 2 mL/h/kg, p = 0.03), and lower dose-corrected AUC than patients with NHL (6010 +/- 836 micrograms x h/L vs. 12,044 +/- 2707 micrograms x h/L, p = 0.006). There was a trend toward faster clearance rates (23 +/- 4 mL/h/kg vs. 16 +/- 3 mL/h/kg, p = 0.1), shorter elimination half-lives (5.7 +/- 3.6 hours vs. 13 +/- 8.8 hours, p = 0.1), and shorter mean residence times (11 +/- 3 hours vs. 25 +/- 5 hours, p = 0.08) for non-Caucasian patients as compared to Caucasian patients. When compared to adult patients, pediatric patients showed a significantly larger volume of distribution at steady state (418 +/- 82 mL/kg vs. 252 +/- 34 mL/kg, p = 0.02) and a longer elimination half-lives (18.4 +/- 13.6 hours vs. 8.7 +/- 6.7 hours, p = 0.04). The pharmacokinetics of B43-Genistein was not affected by the gender of the patients or by bone marrow transplantation in past medical history. Overall, B43-Genistein showed favorable pharmacokinetics in this heavily pretreated leukemia/lymphoma patient population, which is reminiscent of its recently reported favorable pharmacokinetics in cynomolgus monkeys. To our knowledge, this is the first clinical pharmacokinetics study of a tyrosine kinase inhibitor containing immunoconjugate.

Adolescent↗
PubMed1999

Toxicity, biological activity, and pharmacokinetics of TXU (anti-CD7)-pokeweed antiviral protein in chimpanzees and adult patients infected with human immunodeficiency virus.

The purpose of the present study was to evaluate the toxicity and pharmacokinetics of TXU (anti-CD7)-pokeweed antiviral protein (PAP) in human immunodeficiency virus (HIV)-infected chimpanzees and adult patients. At a total dose of 100 microg/kg, TXU-PAP did not cause severe (grade >/= 3) toxicity in any of the four HIV type 1 (HIV-1)-infected or two healthy chimpanzees. The only side effects were a transient elevation of the liver enzyme alanine aminotransferase between days 2 and 14 without a concomitant rise in total bilirubin levels and a decrease in the serum albumin levels between days 1 and 5 without any concomitant weight gain or peripheral edema. TXU-PAP showed favorable pharmacokinetics in chimpanzees with a plasma elimination half-life of 5.1 to 12.0 h and a systemic clearance of 5.8 to 15.1 ml/h/kg. At 2 months after initiation of the TXU-PAP infusions, the HIV-1 burden was reduced to below-detection levels in three of the four chimpanzees, and in the remaining chimpanzee, the HIV burden was <500 RNA copies/ml at 2 weeks but returned to the pretreatment levels by 2 months. TXU-PAP was well tolerated by HIV-1-infected adult patients who received a single 5 microg/kg i.v. infusion of TXU-PAP. TXU-PAP showed very favorable pharmacokinetics in these patients with a relatively long plasma elimination half-life of 12.4 +/- 1.4 h, a mean residence time of 17.9 +/- 2.0 h, and a slow systemic clearance of 2.7 +/- 0.7 ml/h/kg. Concentrations of TXU-PAP required for effective inhibition of HIV-1 replication in preclinical models were achieved in HIV-1-infected patients at the 5 microg/kg dose level without any adverse reactions, and the mean value for AUC was 3059 +/- 721 ng. h/ml. The 1-h postinfusion plasma samples from TXU-PAP-treated patients showed potent anti-HIV activity in vitro and inhibited the replication of HIV in normal peripheral blood mononuclear cells (PBMCs) even at a 1:100 dilution. Although treatment with TXU-PAP at the 5 microg/kg dose level does not provide sustained therapeutic levels, it was capable of reducing the viral burden in six of six patients evaluated. To our knowledge, this is the first report of a clinical pharmacokinetics study of a PAP immunoconjugate in HIV-infected patients. The favorable long plasma elimination half-life of TXU-PAP in combination with its low toxicity provides the basis for further investigation of TXU-PAP as a potential anti-HIV agent.

Adult↗
PubMed1999

Treatment of therapy-refractory B-lineage acute lymphoblastic leukemia with an apoptosis-inducing CD19-directed tyrosine kinase inhibitor.

Seven children and eight adults with CD19+ B-lineage acute lymphoblastic leukemia, as well as one adult with chronic lymphocytic leukemia, were treated with the CD19 receptor-directed tyrosine kinase inhibitor B43-Genistein. All patients had failed previous chemotherapy regimens, and six patients had relapsed after bone marrow transplantation. B43-Genistein was administered as a 1-hour i.v. infusion at 0.1-0.32 mg/kg/day dose levels for 10 consecutive days or 3 consecutive days weekly for a total of nine doses. B43-Genistein was well tolerated by all patients with no life-threatening side effects. There were six episodes of grade 2-3 fever, two of which were clearly drug related, one episode each of grade 3 myalgia, grade 2 sinus tachycardia, and grade 2 vascular leak syndrome. There was one durable complete remission and two transient responses. Pharmacokinetic analyses in 12 patients revealed a plasma half-life of 20 +/- 5 h, mean residence time of 24 +/- 5 h, and a systemic clearance rate of 20 +/- 3 ml/h/kg. Moderate levels of human antimouse antibody (HAMA) ranging from 20-87 ng/ml were detected in the day 28 blood samples from three of nine cases examined. Treatment of these three HAMA-positive patients with a second course of B43-Genistein did not yield measurable immunoconjugate levels in the plasma, indicating that the administered B43-Genistein molecules were rapidly cleared from circulation due to the HAMA. On the basis of its acceptable toxicity profile and its ability to elicit objective responses at nontoxic dose levels, B43-Genistein may provide the basis for an effective treatment strategy for B-lineage acute lymphoblastic leukemia patients who have failed standard therapy.

Adolescent↗
PubMed1999

Community-based malaria control in Tigray, northern Ethiopia.

Community-based control activities have been a major component of the Tigray regional malaria control programme since 1992. A team of 735 volunteer community health workers treat on average 60,000 clinical malaria cases monthly during the high malaria transmission season. Ensuring access for the rural population to early diagnosis and treatment has contributed to a significant decrease in death rate in under-five children at the village level from 1994 to 1996. Mapping and geographic information system (GIS) technologies have been introduced to support planning for control by assessment of community-based coverage. With further development, GIS will be used in stratification, and to assess the impact of water resources development on malaria transmission and intensity.

Adult↗
PubMed1998

Vasopressin-induction of the immediate early gene, NGFI-A, in cultured hippocampal glial cells.

Our earlier autoradiographic work had documented a wide distribution of vasopressin receptors in the hippocampus [R.E. Brinton, K.W. Gee, J.K. Wamsley, T.P. Davis, H.I. Yamamura, Regional distribution of putative vasopressin receptors in rat brain and pituitary by quantitative autoradiography, in: Proc. Natl. Acad. Sci. USA, 81 (1984) pp. 7248-7252; C. Chen, R.D. Brinton, T.J. Shors, R.F. Thompson, [Arg 8]-Vasopressin-induction of long lasting potentiation of synaptic transmission in the dentate gyrus, Hippocampus 3 (1993) 193-203.] which suggested the possibility that receptors for vasopressin were present in both neurons and glia. In the periphery, vasopressin is a potent mitogen in select proliferative cell types [E. Rozengurt, A. Legg, P. Pettican, Vasopressin stimulation of mouse 3T3 cell growth, Proc. Natl. Acad. Sci. USA, 76 (1979) pp. 1284-1287.] which also suggested a possible association between vasopressin receptor activation and the proliferative capacity of astrocytes. We therefore investigated whether vasopressin would induce the expression of the immediate early response gene, NGFI-A (also known as zif/268, ZENK, egr-1, krox 24), which is associated with initiation of mitogenesis [M. Sheng, M.E. Greenberg, The regulation and function of c-fos and other immediate early genes in the nervous system, Neuron, 4 (1990) pp. 477-485.]. Cultured hippocampal glial cells were exposed to vasopressin or a selective V1 vasopressin receptor agonist and in situ hybridization for NGFI-A mRNA was conducted. Results of these experiments demonstrated that vasopressin induced a highly significant dose-dependent increase in the number of cells expressing NGFI-A. Studies to determine the receptor subtype mediating vasopressin induction of NGFI-A were conducted utilizing the specific V1 agonist, [Phe2, Ile3, Orn8]-vasopressin. The V1 receptor agonist induced a highly significant dose dependent increase in the number of grains per NGFI-A positive cell. Time course analysis demonstrated that V1 agonist induction of NGFI-A occurred within 5 min, was maximally induced at 15 min of exposure and exhibited a gradual decline within 30 min of exposure which continued to decline over the 60 min time course. Glial cell responsivity was selective in that vasopressin and V1 agonist induction of NGFI-A occurred in a subpopulation of glial cells. Within a sea of glial cells, vasopressin and V1 agonist would induce islands of NGFI-A positive cells. Results of combined immunocytochemical labeling for the astrocyte specific marker, GFAP, and in situ hybridization for NGFI-A demonstrated that V1 agonist-induced NGFI-A expression occurred in GFAP positive cells. We observed no evidence for V1 agonist induction of NGFI-A in neurons. Collectively, these data document that vasopressin, acting via V1 vasopressin receptors, induces a highly significant increase in NGFI-A expression in select GFAP positive hippocampal astrocytes. To our knowledge, these data are the first report of a vasopressin mediated response in hippocampal glial cells. The potential functional significance of these findings is discussed.

Animals↗
PubMed1997

Evaluation of a nurse-led continence service in the south-west of Glasgow, Scotland.

This paper reports the results of a pilot study of a nurse-led continence promotion service in both the community and a local nursing home. Telephone and written referrals were made to the service from 28 primary care teams in Glasgow, Scotland. In the nursing home all patients were assessed and an appropriate management plan implemented. A full assessment was carried out in all community patients, including an appraisal of contributory factors, urinalysis and diaries of food and drink intake. A management plan suited to the patient was then implemented. Patients' levels of incontinence in both arms of the study were assessed objectively using the Lagro-Janssen method. The cost incurred in both arms of the study were measured. There was a 69% improvement in the level of incontinence in the community group compared with 30% in the residents wing and 13% in the hospital wing. The savings in the nursing home amounted to Pounds 4152 in the residents' wing and Pounds 1959 in the hospital wing. In summary, a nurse dedicated to urinary incontinence in the community allows improved management, a greater level of awareness and results in resource savings, whilst increasing patient accessibility to a service.

Aged↗
PubMed1997

Making the most and making sense: ethnographic research on spirituality in palliative care.

Presents ethnographic research on spirituality in palliative care. Reviews the literature and interviews palliative care staff along with their patients. Discovers two dominant themes in the literature and interviews with staff and patients around spirituality: making the most of it now and making sense. Discusses findings and suggests implications for the practice of spiritual care.

Anthropology, Cultural↗
PubMed1997

Alcohol consumption and blood pressure in recently hospitalised patients.

One-thousand-four-hundred-and-fifty-three patients admitted to a teaching hospital, haemodynamically stable and not severely ill nor in significant pain, were interviewed within 48 h of admission and demographic data and a detailed drinking history were obtained. Supine blood pressures (BP) were recorded on the day following admission. The mean age of the population was 60.5 +/- 19.9 years (range 16-99 years) and the mean reported alcohol consumption was 67.8 +/- 273 g/week (range 0-6125 g/ week). Thirty-six percent of patients were currently receiving antihypertensive drug therapy. On multivariant analysis, reported alcohol intake was not significantly related to systolic BP (beta = 0.000, p = 0.902) or diastolic BP (beta = 0.028, p = 0.281). Age (beta = 0.331, p = 0.0001) and body weight (beta = 0.121, p = 0.0002) were significant independent predictors of systolic BP, and body weight was a significant independent predictor of diastolic blood pressure (beta = 0.207, p < 0.0001). A relationship between alcohol consumption and blood pressure was not apparent in this population of patients following admission to hospital. A positive association between alcohol consumption and blood pressure may not be a universal finding and may be contributed to by a "white coat" effect.

Adolescent↗
PubMed1997

Postmortem sperm procurement.

PURPOSE: We determined the prevalence of requests for postmortem sperm procurement and the degree to which procurement is performed by those working in the field of infertility. MATERIALS AND METHODS: Structured telephone interviews were conducted with personnel at 273 assisted reproductive facilities in the United States and Canada. The number of facilities reporting requests and the number of facilities reporting that they performed the procedure were determined. RESULTS: The prevalence of requests for postmortem sperm procurement was much greater than initially anticipated. A total of 82 requests was reported at 40 facilities in 22 different states between 1980 and 1995. More than half of the reported requests (43) were made between 1994 and 1995. Of the 82 requests 25 were honored at 14 facilities in 11 different states. No requests or procedures were reported from Canada. CONCLUSIONS: Medical advances in postmortem sperm procurement, cryopreservation and in vitro fertilization permit retrieval of sperm after death for various purposes, including posthumous fatherhood. There are no explicit ethical guidelines, legislation or relevant case law, and fertility specialists must confront these issues before proceeding in a field fraught with moral and policy uncertainties.

Cadaver↗
PubMed1997

Improving management of anemia using CQI techniques.

During the last two years, the National Kidney Foundation's Dialysis Outcomes Quality Initiative (NKF-DOQI) Anemia Work Group has been developing clinical practice guidelines for the management of anemia in patients with chronic renal failure. After an in-depth critical analysis of the scientific literature, with a consensus of "expert opinion" used to support recommendations in areas with inadequate published data, evidence-based guidelines were developed. These clinical practice guidelines, regardless of how well-founded in scientific evidence, are likely to be disregarded if they are not applicable in the day-to-day care of patients. Thus, they must be practical, clearly stated, and usable, given available resources and constraints. The purpose of this article is to describe our experiences in implementing some of these guidelines over the last two years, as they were being developed, for the care of patients in our hemodialysis unit.

Anemia↗
PubMed1996

Benzodiazepine prescribing in a Sydney teaching hospital.

OBJECTIVES: To determine the pattern of benzodiazepine prescribing in hospital and at discharge in relation to prior benzodiazepine therapy. DESIGN: Patient interview within 48 hours of admission to determine benzodiazepine, alcohol and other psychotropic drug use before admission and review of medical records after discharge to document drugs prescribed in hospital and at discharge. SETTING: Tertiary teaching hospital, January to August 1995. RESULTS: 1453 patients (mean age, 60 [SD, 19] years; 52.7% female) were interviewed; 277 patients (19.1%) were taking benzodiazepines regularly (one or more doses per week) before admission. Of these, 28.5% did not have benzodiazepine therapy continued while in hospital and 63.9% did not receive benzodiazepines at the time of discharge. Of the remaining 1176 patients (those not previously taking benzodiazepines), 277 (23.6%) were prescribed them for the first time in hospital and 5.3% received benzodiazepines at the time of discharge. Older age, female sex, marital status (single, divorced or widowed) and the use of antidepressants and Schedule 8 narcotic analgesics were all statistically significant predictors of benzodiazepine use before admission, but alcohol consumption was not. CONCLUSIONS: A substantial number of patients do not have their benzodiazepine therapy continued in hospital and at the time of discharge, and are thus at risk of developing benzodiazepine withdrawal syndromes, including delirium. A small but clinically significant number of patients who do not usually take benzodiazepines receive them at the time of discharge and may be at risk of becoming long term users.

Anti-Anxiety Agents↗