PubMed Health⌕ Search

Biomedical subjects

N Kelly

Publications and source records attributed to N Kelly.

At least 19 recordsLinked to original sources
PubMed2002

Molecular epidemiology of coagulase-negative staphylococcal bacteraemia in a newborn intensive care unit.

We isolated 55 coagulase-negative staphylococci (CoNS) over two separate 12-month periods (26 in 1993 and 29 in 1996) from the blood of neonates in a neonatal intensive case unit (NICU) in Melbourne, Australia and compared them by pulse-field gel electrophoresis profile (PFGE), random amplification of polymorphic DNA (RAPD) and antibiogram. The most common species were Staphylococcus epidermidis, S. haemolyticus and S. warneri. The majority of such isolates were resistant to penicillin and to either or both of methicillin and gentamicin. During 1993, there was an increase in the number of CoNS bloodstream infections compared with previous years. S. epidermidis was the most common isolate, with 88% assessed as clinically relevant. Using the three typing systems, we identified one likely epidemic clone of S. epidermidis, the isolates of which were resistant to penicillin, gentamicin and erythromycin and possessed the mecA gene. There was complete correlation between the detection of mecA and the phenotypic expression of resistance when zone diameters in the disc diffusion assay were interpreted according to the latest NCCLS guidelines (1999). Profiles of the remaining 1993 isolates were generally heterogeneous, suggesting independent acquisition with some evidence of cross-infection. The predominant bloodstream isolates in 1996 were heterogeneous multi-resistant strains of S. epidermidis, S. haemolyticus and S. warneri, about half of which were assessed as clinically relevant. These data support the view that CoNS are significant nosocomial pathogens in NICU and that resistant clones may be transmitted between babies. Molecular epidemiological tools are helpful for understanding transmission patterns and sources of infection, and are useful for measuring outcomes of intervention strategies implemented to reduce nosocomial CoNS sepsis. PFGE was found to be more discriminatory than RAPD, but the latter provides results in a more timely manner.

Australia↗
PubMed2001

Reduction of animal usage by serial bleeding of mice for pharmacokinetic studies: application of robotic sample preparation and fast liquid chromatography-mass spectrometry.

Typically, pharmacokinetic studies in mice require one animal per time point, thus resulting in differences due to dosing error, animal to animal variation and more importantly the euthanasia of a large number of animals. A method for the determination of pharmacokinetic data from serially bled mice to support early drug discovery is described. Sample analysis relies on liquid chromatography coupled with tandem mass spectrometry permitting robust and reproducible analysis requiring approximately 3 min per sample. Several parameters are discussed including the method of sample collection, preparation and analysis. The use of serially bled mice has lead to a remarkable reduction in animal usage and a corresponding reduction in compound required for such experiments. Using conventional methodology, a nine-point pharmacokinetic curve with four animals per time point would require 36 mice. With the method described below, only four mice in total are used and euthanasia is not required, permitting reuse after several weeks recovery and washout. Also, pharmacodynamic-pharmacokinetic correlation is possible and is demonstrated using a mouse model of diabetes.

Animals↗
PubMed2001

'RETCIF': a rapid, sensitive method for detection of viruses, applicable for large numbers of clinical samples.

Rapid detection of viruses in clinical samples is important for continuing appropriate antiviral treatment and discontinuing unnecessary antibacterial treatment, as well as for excluding viral pathogens. Yet detection of viral agents may require numerous susceptible cell lines. Even with the shell vial culture method, it is cumbersome for handling large volumes of specimens. A procedure has been developed, which is time and cost-saving and uses specific cell lines in a 96-well microtitre plate and monoclonal antibodies (RETCIF-rapid enhanced tissue culture immunofluorescence). Each clinical sample was inoculated into 12 different wells with five different cell lines. Enhancement was achieved by sonication, centrifugation and hormonal supplementation to the medium used. Cytomegalovirus (CMV), herpes simplex virus (HSV) and respiratory viruses were detected by monoclonal antibodies on day 2, whilst varicella zoster virus (VZV) and enteroviruses were detected on days 5 and 7, respectively. During July-December 1998, 3298 patient specimens were compared by RETCIF and a modified shell vial method. Either or both methods isolated 779 viruses (24% positivity rate), whilst both methods detected 621. Of the 779 viruses, 87% (679) were isolated by the shell vial method in an average time of 4.9 days. For RETCIF the respective rate was 92.5% (721), in an average time of 3.0 days. The RETCIF method is a time-saving procedure, with higher isolation rates than the shell vial method.

Antibodies, Monoclonal↗
PubMed2001

Absence of immunopathology associated with repeated IV administration of bovine Hb-based oxygen carrier in dogs.

BACKGROUND: A Hb-based oxygen carrier, HBOC-301, is licensed by the FDA for use as a single-dose product to treat anemia in canines. The objective of this study was to investigate the immunopathologic consequences of multiple doses of HBOC-301. STUDY DESIGN AND METHODS: HBOC-301 was administered intravenously at 1.3 g per kg (10 mL/kg) nine times over 50 weeks to each of eight splenectomized beagles. During interim weeks, HBOC-301-specific IgG antibody was quantified in serum by immunoassay. Immunofluorescence studies were performed on thin sections of control and test dog livers and kidneys to detect any IgG, IgM, IgA, or C3 deposition. Physiology (p50) studies evaluated the capacity of circulating HBOC-301-specific IgG antibody to competitively block the binding of oxygen to HBOC-301. RESULTS: HBOC-301-specific IgG antibody was detected in seven of eight HBOC-301-treated dogs by Week 6. Peak antibody levels occurred by Week 10 (after the third dose). Immunofluorescence studies detected comparable IgG, IgA, IgM, or C3 deposition patterns in the kidneys and livers of both control and test dogs, which indicated no selective antibody-mediated deposition from multiple HBOC-301 administrations. Moreover, HBOC-301-specific IgG antibody in serum was unable to inhibit oxygen binding to the HBOC-301 in vitro, which indicated that circulating antibody did not diminish the oxygen-binding capacity of HBOC-301. CONCLUSION: The immunologic, histologic, and physiologic data support the safety of multidose administration of HBOC-301 in canines.

Anemia↗
PubMed2000

Breast cancer: better care for less cost. Is it possible?

OBJECTIVES: To estimate the potential for cost reduction in the acute care setting and the required investment in the home care setting of implementing an outpatient/early discharge strategy for operable (stages I and II) breast cancer in Canada. METHODS: Data from a community hospital were augmented by expert knowledge and incorporated into the breast cancer submodel of Statistics Canada's Population Health Model. For the estimated 90% of patients for whom this approach was assumed to be appropriate, the resource utilization for outpatient breast-conserving surgery and 2 days of hospitalization for those women undergoing mastectomy was quantified and costed, as were the appropriate home care services. A 5% readmission rate for complications was assumed. Cost per case, total cost burden, investment in home care, savings in acute care, and net savings were calculated. Sensitivity analyses were performed around readmission rates and home care/surgical follow-up costs. All costs were determined in 1995 Canadian dollars. RESULTS: The cost of initial treatment for the 15,399 women diagnosed with stages I and II breast cancer in 1995 in Canada was estimated to be $127.6 million. Hospitalization made up 53% of these costs. Under the outpatient/early discharge strategy, the acute care cost of initial breast cancer management could be reduced by $47.2 million, with an investment in home care of $14.5 million ($453 per patient), resulting in an overall net saving of $33 million. Under this strategy, hospitalization would contribute only 21% to the total care cost. CONCLUSIONS: If Canadian surgeons and healthcare administrators were to work together to put in place processes to support ambulatory breast cancer surgery and if resources were redirected to the provision of home-based post-operative care, there would be potential for a large net healthcare saving and preservation of high-quality patient care.

Algorithms↗
PubMed2000

Is antenatal group B streptococcal carriage a predictor of adverse obstetric outcome?

OBJECTIVES: While early-onset neonatal GBS sepsis is positively associated with premature birth and prolonged rupture of membranes, there is debate in the literature as to whether maternal GBS colonization is a predictor of adverse obstetric outcome. This is a critical issue to resolve for appropriate management (expectant vs. interventional management) of the patient presenting with premature rupture of membranes, who has no overt signs of sepsis, but who is colonized with GBS. METHODS: Since 1981 it has been hospital policy to screen all public patients antenatally for genital carriage of GBS by collection of a low vaginal swab at 28-32 weeks. All patients colonized with GBS antenatally are given penicillin as intrapartum chemoprophylaxis. Review of all GBS-colonized antenatal patients for a 12-month period (580 of 4,495 patients) and a randomized (every fourth consecutive antenatal patient) number of noncolonized patients (958) was made. Lower vaginal GBS colonization and other risk factors for preterm delivery were assessed using univariate and multivariate generalized linear modeling. RESULTS: In the study group, the maternal GBS colonization rate was 12.9%. When cofounding variables were controlled in a multivariate analysis, the association between antepartum GBS colonization and preterm labor and preterm rupture of membranes was not significant. CONCLUSION: Maternal antenatal carriage of GBS does not predict preterm labor. Therefore it is appropriate that expectant management occur for a GBS-colonized woman who ruptures her membranes, is not in labor, and has no evidence of sepsis.

Australia↗
PubMed2000

Trypanosoma cruzi infection of squirrel monkeys: comparison of blood smear examination, commercial enzyme-linked immunosorbent assay, and polymerase chain reaction analysis as screening tests for evaluation of monkey-related injuries.

BACKGROUND AND PURPOSE: Wild-caught New World monkeys (NWM) from Central or South America are often infected with Trypanosoma species, including T. cruzi. In humans, T. cruzi causes Chagas' disease. Even in closed monkey colonies, T. cruzi can be propagated by blood-to-blood exposure, sexual activity, and transplacental transmission. Animal handlers and laboratory staff who deal with blood and tissues from infected NWM are at riskfor acquiring Chagas' disease via accidental exposure. METHODS: We screened 162 blood samples from wild-caught Saimiri sp. monkeys for Trypanosoma species infections by use of blood smear examination, ELISA, and polymerase chain reaction (PCR) analysis. Blood samples from 19 employees with recent history of monkey-associated injuries also were tested. RESULTS: Six percent (10/162) of the monkey samples were T. cruzi positive on the basis of blood smear examination results, 10.4% (17/162) were positive by ELISA results, and 26.5% (43/162) were positive by PCR results. Other organisms identified by PCR analysis included T. rangeli in two animals, Plasmodium spp. in two animals (P. malariae confirmed by PCR results) and microfilariae in one animal (morphologically, Mansonella perstans). Evidence of trypanosome infection was not found in the 19 employee samples on the basis of results of any of the three aforementioned tests. CONCLUSIONS: Close attention must be paid to worker safety where wild-caught NWM are used. The PCR analysis has a clear advantage over conventional techniques (ELISA, blood smear) for screening NWM for trypanosome infections during quarantine and after employee injury.

Animal Husbandry↗
PubMed1997

Political rape as persecution: a legal perspective.

The use of rape as a tool of persecution is not new, but recognition of the political rape of women as a violation of internationally protected human rights and as a basis for political asylum is. Over the last several years, a number of advances have been made, including human rights instruments that recognize the need to protect women from rape and other sexual abuse; guidelines from the United Nations High Commission for Refugees and several countries that acknowledge the political nature of rape and the difficulties experienced by women attempting to assert claims to asylum based on rape or other sexual abuse; and a number of important decisions by individual governments to provide protection to survivors of rape. Legal advancements for women in this area have depended largely on the assistance of medical and psychological experts who have been able to educate adjudicators and advocates on the effects of sexual harm, provide expert testimony in individual asylum cases, and provide critical treatment and support to survivors as they work their way through the process of obtaining legal protection.

Female↗
PubMed1996

Further studies on the bioaffinity chromatography of NAD(+)-dependent dehydrogenases using the locking-on effect.

Previous studies have capitalized on ordered kinetic mechanisms in the design of biospecific affinity chromatographic methods for highly efficient purifications and mechanistic studies of enzymes. The most direct tactic has been the use of immobilised analogues of the following, usually enzyme-specific substrates, e.g., lactate/pyruvate in the case of lactate dehydrogenase for which NAD+ is the leading substrate. Such immobilised specific substrates are, however, often difficult or impossible to synthesise. The locking-on strategy reverses the tactic by using the more accessible immobilised leading substrate, immobilised NAD+, as adsorbent with soluble analogues of the enzyme-specific ligands (e.g., lactate in the case of lactate dehydrogenase) providing a substantial reinforcement of biospecific adsorption sufficient to effect adsorptive selection of an enzyme from a group of enzymes such as the NAD(+)-specific enzymes. The value of this approach is demonstrated using model studies with lactate dehydrogenase (LDH, EC 1.1.1.27), alcohol dehydrogenase (ADH, EC 1.1.1.1), glutamate dehydrogenase (GDH, EC 1.4.1.3) and malate dehydrogenase (MDH, EC 1.1.1.37). Purification of bovine liver GDH in high yield from crude extracts is described using the tactic.

Affinity Labels↗
PubMed1995

Early-onset neonatal group B streptococcal sepsis: economics of various prevention strategies.

OBJECTIVES: To evaluate three strategies for preventing group B streptococcal neonatal sepsis in large teaching hospitals and to examine their cost effectiveness and cost benefit. METHODS: A decision tree was constructed to determine the outcome of three prevention strategies: (1) Screen all pregnant women for group B streptococcus (GBS) at 28 weeks' gestation and give intrapartum chemoprophylaxis to all GBS carriers; (2) Screen all pregnant women, but give chemoprophylaxis selectively to those carriers with obstetric risk factors (i.e., premature labour, prolonged rupture of membranes and maternal sepsis); and (3) Do not screen but give intrapartum chemoprophylaxis for all women with obstetric risk factors. Australian data were used if available, and the cost benefit and cost effectiveness of each strategy compared with no screening at all were estimated. RESULTS: All three strategies had a net cost benefit compared with no intervention at all. Strategy 1 could prevent 46%, Strategy 2 38% and Strategy 3 60%-80% of all early-onset GBS sepsis. CONCLUSION: A substantial proportion of early-onset GBS sepsis is preventable. Strategy 1, which is practical in some large teaching hospitals, prevents more sepsis at a lower cost per case prevented than Strategy 2. Strategy 3 theoretically could prevent more cases at a substantially lower cost than Strategies 1 or 2, but has not been evaluated clinically.

Cost-Benefit Analysis↗
PubMed1995

Bioactive tumor necrosis factor in the sputa of cystic fibrosis patients.

Eighty sputum samples from 37 cystic fibrosis patients were assayed for tumor necrosis factor alpha (TNF-alpha) in the L929 bioactivity assay. In addition, the presence of TNF-alpha-specific mRNA in the sputum was determined by using TNF-alpha-specific DNA probes in a PCR amplification step after reverse transcription of the mRNA to cDNA. Bioactive TNF-alpha was detected in 69 (86%) of the 80 sputum samples tested and, on at least one occasion, in 35 (95%) of the 37 cystic fibrosis patients sampled. The highest levels of TNF-alpha were observed in sputa obtained from patients presenting with an exacerbation of their disease.

Adult↗
PubMed1995

Impact of race and ethnicity on ischemic stroke. The University of California at San Diego Stroke Data Bank.

BACKGROUND AND PURPOSE: As the US minority population continues to grow, increasing numbers of nonwhite citizens are at risk for stroke. A better understanding of how ischemic stroke differs in the minority populations may lead to more effective clinical management. METHODS: We prospectively evaluated 542 consecutive patients (416 whites, 71 Mexican Americans, 55 blacks) presenting to the University of California at San Diego Medical Center or the San Diego Veterans Affairs Hospital with presumed acute ischemic stroke or transient ischemic attack. RESULTS: Whites had a higher proportion of transient ischemic attacks (32% versus 18% and 17% for blacks and Mexican Americans, respectively) and had the lowest prevalence of diabetes mellitus (17% versus 29% and 40% for blacks and Mexican Americans, respectively). Mexican Americans had higher initial serum glucose levels (178 versus 133 and 131 mg/dL for whites and blacks, respectively). Blacks were youngest (average age, 56 years). There were no differences among the groups in the prevalence of prior stroke, hypertension, myocardial infarction, or smoking; initial systolic blood pressure, serum cholesterol levels, and functional deficit also were similar. Although it did not reach statistical significance, there was a trend toward relatively late presentation in the black stroke subpopulation: only 53% of blacks (compared with 73% of both Mexican Americans and whites) reached medical attention within 24 hours of stroke onset. All groups had similar diagnostic evaluations and functional outcome at 1 week. With the exception of a higher frequency of stroke of unknown cause in Hispanics, the distributions of stroke etiologies did not differ significantly among the groups. CONCLUSIONS: These data suggest that there are significant clinical differences in populations with ischemic stroke and transient ischemic attack that are related to race and ethnic origin, but in our population these differences did not include the extent of diagnostic evaluation undertaken or stroke severity.

Acute Disease↗
PubMed1995

The importance of a lipopolysaccharide-initiated, cytokine-mediated host defense mechanism in mice against extraintestinally invasive Escherichia coli.

Extraintestinally invasive Escherichia coli (EC) that possess both a complete LPS and K1 capsule evade both complement-mediated bacteriolysis and neutrophil-mediated killing. Since C3H/HeJ mice that are hyporesponsive to LPS were uniquely susceptible to lethal infection with EC of this phenotype, we speculated there was an LPS-initiated host defense mechanism against this pathogenic phenotype. The LPS-normoresponsive C3H/HeN as well as the C3H/HeJ mice cleared these EC from the circulation within 4 h of intravenous administration. Whereas electron micrographs of the liver demonstrated these EC undergoing degeneration within the phagolysosomes of of both macrophages and Kupffer cells of C3H/HeN mice, these EC replicated within these cells of the C3H/HeJ mice. Restoration of anti-EC activity of C3H/HeJ mice occurred with activation of Kupffer cells and peritoneal macrophages in vivo with BCG and in vitro with IFN-gamma, but not with LPS. Pretreatment of C3H/HeJ mice with a combination of recombinant murine IL-1 and TNF-alpha also restored the killing of K1(+)-EC but did not enhance the killing of a K1(-)-EC mutant. These data are consistent with the hypothesis that (a) there is no intrinsic inability of C3H/HeJ phagocytes to kill EC, but (b) an LPS-initiated, cytokine-mediated host defense mechanism is required for such killing. These studies emphasize the importance of bacterial surface characteristics in the interaction with specific host defenses.

Animals↗