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Biomedical subjects

S Richardson

Publications and source records attributed to S Richardson.

At least 55 records · Page 3Linked to original sources
PubMed2000

"Lively combat": Kathleen Ellis and the Canadian Nurses Association's lobby during the Second World War.

Although it has become unfashionable in recent years to extol the achievements of those who have become known as the "elite" in Canadian nursing, it is nonetheless true that a number of early Canadian nurse leaders contributed significantly to the advancement of their profession. One such individual was Kathleen Wilhelmina Ellis. This article analyzes her impact as Emergency Nursing Advisor for the Canadian Courses Association (CNA) during World War II. The previously unreported success of the CNA in capitalizing on the "crisis" of world War II to counter plans of the Canadian Hospital Council to increase pupil nurse enrollments beyond hospitals' clinical teaching and supervision capabilities provides the context for analysis. From 1942 to 1946, the CNA administered a $774,000 grant from the Federal Government to improve teaching in hospital and university schools of nursing, provide bursaries for graduate nurses, and recruit increased numbers of qualified applicants to hospital nurse training programs. The success of the CNA in securing and administering these funds signalled its political acumen as national representative of Canadian nurses and nursing. Kathleen Ellis' contribution as Emergency Nursing Advisor for the CNA was important to the success of the CNA's lobby during World War II.

Canada↗
PubMed2000

Agar gel immunodiffusion test for the detection of bovine leukemia virus antibodies: lack of trans-Atlantic standardization.

Two agar gel immunodiffusion (AGID) kits for the serodiagnosis of bovine leukemia virus (BLV) were imported from Europe and were compared with North American kits. The BLV AGID kits from North America and from Europe differed significantly. The punches were different, as were the pattern distribution in the agar of the reference and the test sera, resulting in differences in the reading of the immunoprecipitation lines. Based on the testing of 1200 serum samples from cattle, the European kits gave a good correlation with the American kits, as indicated by their respective kappa values. However, the European kits were found to be less sensitive when evaluated against weakly positive samples from field specimens or following a dilution trial. Only 65% and 50% of the weakly positive samples detected by the American kit #1 were detected by the European kits #2 and #3, respectively. The American kit was also capable of detecting BLV antibodies in 45% of strongly positive samples diluted 1/50 in negative sera, while antibodies were detected in only 15% of the samples with the European kit #2 and in none of the samples with the European kit #3. False negatives were also detected with the European kits. Among the false negatives, the degree of expected reactions was weak (European kit #2) or of varying degrees of positivity (European kit #3). Besides the differences in format and performance, the BLV-AGID kits in Europe are evaluated with the National Standard Serum E4 while a proficiency panel composed of a quadruplicate set of 10 reference sera is used in Canada to monitor the kits. Based on the overall observations, we noted a lack of standardization between the BLV-AGID kits used in North America and in Europe.

Agar↗
PubMed2000

Enzyme-linked immunosorbent assay for the diagnosis of bovine leukosis: comparison with the agar gel immunodiffusion test approved by the Canadian Food Inspection Agency.

Four commercially available bovine leukemia virus (BLV)-ELISA kits from Europe or the United States were compared to the agar gel immunodiffusion (AGID) test officially approved by the Canadian Food Inspection Agency (CFIA). A total of 1200 cattle serum samples were used. Three ELISA kits based on the envelope glycoprotein (gp51) gave an excellent correlation with the AGID test. The kappa values were 0.998, 0.984, and 0.986 for the ELISA kits #1, #2, and #3, respectively. The ELISA kit based on the p24 core protein was found to be less sensitive than the officially approved AGID test and detected 5.13% of false negatives. Forty BLV AGID strongly positive serum samples were diluted. Based on the dilution experiment, the gp51 ELISA kits were found to be more sensitive than the AGID test kits. They were capable of detecting antibodies in samples diluted up to 1/5000 (kit #1), 1/20 800 (kit #2) and 1/4000 (kit #3), whereas the AGID kit was only capable of detecting antibodies in samples diluted up to 1/100. Based on these observations, the gp51 BLV-ELISA was recognized as an official test method for the serodiagnosis of bovine leukosis in Canada.

Agar↗
PubMed1999

Timing of human immunodeficiency virus type 1 (HIV-1) transmission from mother to child: bayesian estimation using a mixture.

The timing of mother-to-child HIV transmission is not directly observable but influences the infected child's viral and immune status in the neonatal period. A hierarchical model was developed in a Bayesian framework to 'back-calculate' the timing of HIV-1 transmission from mother to child from the virological and immunological kinetics in the infected infant. Joint evolution of viral markers and immune response was modelled as a continuous time Markov process. The modelling of the period from infection to birth was based on a mixture of three distributions taking into account the various mother-to-child transmission pathways: In utero (early or late in gestation) and intrapartum (during the delivery process), integrating the fact that transmission is a continuum during the pregnancy. Gibbs sampling was used to estimate the marginal posterior distributions of the transition intensities between stages of HIV infection and those of the individual times from infection to birth. We applied our model to data on 135 perinatally HIV-1-infected children included in the French Prospective Study on Pediatric HIV infection. The model suggested that transmission occurred late in utero during the last month of pregnancy and that the day of delivery was a particularly critical time in HIV-1 transmission from mother to child. The paper ends with a discussion of model assumptions and a comparison with results obtained using a non-parametric method.

Antibodies, Viral↗
PubMed1999

Optimisation of electroporation for biochemical experiments in live cells.

To introduce into cells small molecules, which do not permeate the cell membrane naturally, electroporation is the fastest and most efficient technique. Although it is not completely benign, the speed at which a full population of cells can be permeated gives it a strong advantage over all other cell permeation techniques. Here we describe the potential damaging effects of electroporation and how to derive conditions which avoid these and assure its use for biochemical experiments in live cells.

Annexin A5↗
PubMed1999

Adolescent occupational injuries: Texas, 1990-1996.

BACKGROUND: A comprehensive surveillance system for occupational injuries to adolescents does not exist in Texas, as in most states. Therefore, the magnitude, severity, nature, and source of injuries to working adolescents have not been well described in Texas. METHODS: The investigators used three data sources to investigate work-related injuries and deaths in Texas: (1) Texas Workers' Compensation Commission (TWCC) claims data from 1991 through April 1996; (2) 1993 TWCC/Bureau of Labor Statistics (BLS) Annual Survey of Occupational Injuries and Illnesses; and (3) work-related fatalities identified from Texas death certificates from 1990-1995. RESULTS: There were 9,027 injuries reported to the TWCC for adolescents 14-17 years of age during slightly more than 5 years. Injuries for which indemnity payments were made (more than 7 days out of work) occurred among 21.7% of the adolescents. Based on BLS data in 1993, of 992 non-fatal injuries involving days away from work, 35% were caused by contact with objects, 27% by bodily reaction, and 24% by falls. Two-thirds of these injuries occurred while working in eating and drinking places and grocery stores. Three-quarters of the 30 deaths from 1990-1995 were accounted for equally by motor vehicle and homicide. CONCLUSIONS: In conclusion, a substantial number of adolescents are injured or killed in the workplace each year in Texas. Although improved population-based surveillance is needed, sufficient knowledge exists to begin prevention efforts now.

Accidents, Occupational↗
PubMed1999

Mechanism of 3-methylaspartase probed using deuterium and solvent isotope effects and active-site directed reagents: identification of an essential cysteine residue.

The mechanism of the L-threo-3-methylaspartate ammonia-lyase (EC 4.3.1.2) reaction has been probed using deuterium and solvent isotope effects with three different substrates, (2S,3S)-3-methylaspartic acid, (2S)-aspartic acid and (2S,3R)-3-methylaspartic acid. Each substrate appears to form a covalent adduct with the enzyme through the amination of a dehydroalanine (DehydAla-173) residue. The true substrates are N-protonated and at low pH, the alkylammonium groups are deprotonated internally in a closed solvent-excluded pocket after K+ ion, an essential cofactor, has become bound to the enzyme. At high pH, the amino groups of the substrates are able to react with the dehydroalanine residue prior to K+ ion binding. This property of the system gives rise to complex kinetics at pH 9.0 or greater and causes the formation of dead-end complexes which lack Mg2+ ion, another essential cofactor. The enzyme-substrate adduct is subsequently deaminated in two elimination processes. Hydrazines act as alternative substrates in the reverse reaction direction in the presence of fumaric acid derivatives, but cause irreversible inhibition in their absence. Borohydride and cyanide are not inhibitors. N-Ethylmaleimide also irreversibly inactivates the enzyme and labels residue Cys-361. The inactivation process is enhanced in the presence of cofactor Mg2+ ions and Cys-361 appears to serve as a base for the removal of the C-3 proton from the natural substrate, (2S,3S)-3-methylaspartic acid. The dehydroalanine residue appears to be protected in the resting form of the enzyme by generation of an internal thioether cross-link. The binding of the substrate and K+ ion appear to cause a conformational change which requires hydroxide ion. This is linked to reversal of the thioether protection step and generation of the base for substrate deprotonation at C-3. The deamination reaction displays high reverse reaction commitments and independent evidence from primary deuterium isotope effect data indicates that a thiolate acts as the base for deprotonation at C-3.

Ammonia↗
PubMed1999

Stochastic algorithms for Markov models estimation with intermittent missing data.

Multistate Markov models are frequently used to characterize disease processes, but their estimation from longitudinal data is often hampered by complex patterns of incompleteness. Two algorithms for estimating Markov chain models in the case of intermittent missing data in longitudinal studies, a stochastic EM algorithm and the Gibbs sampler, are described. The first can be viewed as a random perturbation of the EM algorithm and is appropriate when the M step is straightforward but the E step is computationally burdensome. It leads to a good approximation of the maximum likelihood estimates. The Gibbs sampler is used for a full Bayesian inference. The performances of the two algorithms are illustrated on two simulated data sets. A motivating example concerned with the modelling of the evolution of parasitemia by Plasmodium falciparum (malaria) in a cohort of 105 young children in Cameroon is described and briefly analyzed.

Algorithms↗
PubMed1999

Multilocus genotypes and DNA fingerprints Do not predict variation in azole resistance among clinical isolates of Candida albicans.

If variation in azole resistance is due to inherent differences in strains of Candida albicans, as a predominantly clonal organism, then correlation between multilocus genotypes and drug resistance would be expected. A sample of 81 clinical isolates from patients infected with human immunodeficiency virus in Toronto, Canada, plus 3 reference isolates were genotyped at 16 loci, distributed on all linkage groups, by means of oligonucleotide hybridizations specific for each of the alleles at each locus. These multilocus genotypes were significantly correlated with DNA fingerprints obtained with the species-specific probe 27A, indicating widespread linkage disequilibrium in the genome. There were 64 multilocus diploid genotypes and 77 DNA fingerprint types delineated in this sample. Neither the multilocus genotyping nor DNA fingerprinting alone identified all of the 81 types identified by the combination of these two methods. Multilocus genotypes were not predictive of fluconazole resistance, suggesting that resistance is gained or lost too quickly to be predicted by linkage with neutral markers.

Antifungal Agents↗
PubMed1999

Poly(amidoamine)s as potential endosomolytic polymers: evaluation in vitro and body distribution in normal and tumour-bearing animals.

Fusogenic peptides derived from viral coat proteins cause perturbation of the endosomal membrane and are often used to improve the transfection efficiency of non-viral vectors in vitro. However, fusogenic peptides have limited potential for use in vivo due to their inherent immunogenicity. Totally synthetic polymers that are endosomolytic should circumvent this problem and could be useful as components of non-viral delivery systems as long as they do not immediately localise in the liver after intravenous (i.v.) injection. Linear poly(amidoamine) polymers (PAAs) having amido- and tertiary amino-groups along the main polymer undergo pH-dependent conformational change and thus provide an ideal opportunity for design of polymers that display membrane activity at low pH. Here we describe four PAAs, ISA 1 (Mn = 6900 Da) and ISA 23 (Mn = 10,500 Da) and their analogues ISA 4 and ISA 22 (Mn approximately 8000 Da) containing approximately 1 mol% 2-p-hydroxyphenyl ethylamine to allow radioiodination and thus monitoring of their biodistribution. In vitro cytotoxicity was assessed by MTT assay after incubation of PAAs with B16F10 and Mewo cell lines. The IC50 values observed for all PAAs were > 2 mg/mL in comparison with poly(L-lysine) which displayed an IC50 in the range 0.01-0.1 mg/mL. At pH 7.4 none of the PAAs studied was haemolytic at 1 h at concentrations below 3 mg/mL. PAAs were subsequently incubated with rat red blood cells for 24 h (1 mg/mL) at different pHs. In contrast to poly(L-lysine) which was haemolytic at pH 7.4, 6.5 and 5.5, none of the PAAs was lytic at pH 7.4, but they became membrane active at lower pH (approximately 45% for ISA 4, 50% for ISA 22 and 90% for ISA 23). These observations were substantiated by SEM and confirm the pH-dependence of membrane activity. After i.v. injection to rats 125I-labelled ISA 4 was immediately taken up by the liver (> 80% recovered dose at 1 h) whereas 125I-labelled ISA 22 was not (liver uptake was < 10% recovered dose at 5 h). Furthermore, biodistribution studies in mice bearing subcutaneous B16F10 melanoma showed that 125I-labelled ISA 22 was still accumulating in tumour tissue after 5 h (2.5% dose/g). PAAs have potential as endosomolytic agents and quantitation of the endosome to cytoplasm transfer is warranted after i.v. administration.

Animals↗
PubMed1999

Emergency departments and the inappropriate attender--is it time for a reconceptualisation of the role of primary care in emergency facilities?

The appropriateness of Emergency Department (ED) usage is often questioned, with recognition at an international level of the growing prevalence of 'inappropriate attenders'. This term is used to describe individuals who present for treatment that could more appropriately be provided in the primary health care setting. This is an issue of concern for staff working in New Zealand Emergency Departments. The present article offers a review of currently identified issues concerning ED attendance, and examines the core question of the role of primary care in the Emergency Department. It asks whether this is an appropriate use of ED resources, and if so, what are the implications for the role of the emergency nurse?

Emergency Nursing↗
PubMed1998

Injection of the protein kinase C inhibitor Ro31-8220 into the nucleus accumbens attenuates the acute response to amphetamine: tissue and behavioral studies.

The ability of amphetamine to produce heightened locomotor activity is thought to be due to its ability to enhance dopamine release from mesolimbic dopamine neurons. The mechanism by which amphetamine increases dopamine release is not well understood, but is thought to involve exchange diffusion with synaptosomal dopamine through the dopamine transporter. We recently reported that amphetamine-mediated dopamine release in the striatum is also dependent on protein kinase C activity. In the current study, we investigated the role of protein kinase C activity in the acute neurochemical and behavioral response to amphetamine in the nucleus accumbens. Consistent with previous results in the striatum, amphetamine-stimulated dopamine release from nucleus accumbens tissue was inhibited by the specific protein kinase C inhibitor Ro31-8220, but not by the relatively inactive analog bisindoylmaleimide V. In addition, the effects of protein kinase C activity on the acute behavioral response to amphetamine was examined by injecting Ro31-8220 into the nucleus accumbens 15 min prior to intra-accumbens amphetamine. Pretreatment with Ro31-8220 attenuated the motor-stimulant effects of intra-accumbens amphetamine relative to control subjects pretreated with vehicle. Bisindoylmaleimide V did not significantly inhibit the motor-stimulant effects of intra-accumbens amphetamine. These results suggest that the action of amphetamine in the nucleus accumbens in increasing dopamine release and locomotor activity is dependent on protein kinase C activity.

Amphetamine↗
PubMed1998

Extended excretion of rotavirus after severe diarrhoea in young children.

BACKGROUND: Rotaviruses are the major cause of severe childhood diarrhoea. Knowledge of the natural history of infection, including duration of intestinal virus shedding, is important in the understanding of transmission, sources of infection, and immune responses. METHODS: We carried out a study of rotavirus excretion in 37 children admitted to hospital with severe rotavirus diarrhoea. Sequential faecal specimens were collected from each child during 100 days of surveillance, and screened for rotavirus by EIA and by amplification of genome double-stranded RNA by reverse-transcription PCR. IgA coproantibody was estimated by EIA. FINDINGS: Duration of rotavirus excretion ranged from 4 to 57 days after onset of diarrhoea. Excretion ceased within 10 days in 16 (43%) children, and within 20 days in 26 (70%) children. Extended excretion was detected for 25-57 days in the remaining 11 (30%) children owing mainly to continued excretion of the primary infecting strain. Extended excretion was significantly associated with antirotavirus IgA coproantibody boosts during 100 days of surveillance (p=0.001, log-rank test), and with recurrence of mild diarrhoea symptoms during convalescence (p=0.006, Fisher's exact test). INTERPRETATION: Severe rotavirus disease in young children may be followed by extended excretion of rotavirus. The risk of transmission to others may be greater than previously believed. Extended excretion could also explain some cases of the postgastroenteritis syndrome.

Antibodies, Viral↗
PubMed1998

Optimal membrane choice for microdialysis sampling of oligosaccharides.

An analytical methodology based on microdialysis sampling, high-performance anion-exchange chromatography and integrated pulsed electrochemical detection for the monitoring of oligosaccharides in bioprocesses is presented. Amylopectin and model maltooligosaccharide standards; glucose, maltose, maltotriose, maltotetraose, maltopentaose, maltohexaose and maltoheptaose were used to demonstrate its versatility in view to sampling in enzymatic bioprocesses. The performance and characteristics of membranes with the same cut-off ranging between 3 and 100 kDa, were evaluated with respect to their extraction fraction (EF), permeability factors, temperature stability and protein (enzyme) interaction. All investigated membranes showed some non-specific interaction with enzymes. The EF and non-specific membrane-enzyme interactions were higher for the polysulfone membranes compared with the polyamide and polyethersulfone membranes. For all saccharides, the EF was independent of the concentration even for a 250-fold change in concentration. The EF and morphology of the membranes in their dehydrated state, as observed using scanning electron microscopy did not show any significant difference between membranes exposed to a 90 degrees C temperature for 3 and 24 h indicating their applicability to the study of high temperature bioprocesses.

Algorithms↗
PubMed1998

Effect of potent urease inhibitor, fluorofamide, on Helicobacter sp. in vivo and in vitro.

The therapeutic potential of urease inhibition of Helicobacter pylori has been studied by examining the effect of the potent urease inhibitor, fluorofamide (N-(diaminophosphinyl)-4-fluorobenzenamide), on urease activity and bacterial survival in vivo and in vitro. In culture, acid protection in H. pylori was shown to be due to changes in the pH of the medium brought about by the release of ammonia. Both the acid protection and the ammonia release were completely blocked by fluorofamide at low doses (ED50 = approximately 100 nM). However, fluorofamide was unstable under acidic conditions (T1/2 = 5.7 min at pH 2). Despite this, fluorofamide was the best available compound to test in vivo. In ferrets naturally infected with H. mustelae, a single dose (50 mg/kg, per os) of fluorofamide completely inhibited bacterial urease. In repeat dosing studies, fluorofamide (50 mg/kg per os, three times a day) was compared with the Helicobacter triple therapy regime (amoxycillin, metronidazole, and bismuth subcitrate). Fluorofamide failed to eradicate the H. mustelae infection, compared to 80% eradication with triple therapy. However, histological samples showed a profound reduction in bacterial numbers following fluorofamide treatment. A combination of fluorofamide and amoxycillin was dosed to ferrets (seven days of treatment with 50 mg/kg fluorofamide plus 10 mg/kg amoxycillin per os twice a day); however, this failed to eradicate the infection, despite there being a reduction in bacterial numbers in 3/5 ferrets after 21 days after dosing stopped. It was concluded that urease inhibitors (either alone or in combination with antibiotics) are unlikely to have therapeutic potential for Helicobacter pylori infections. This is probably because, in vivo, some bacteria (perhaps dormant forms) are not entirely dependent upon urease for survival. However, given the acid instability of fluorofamide, the possibility that more stable urease inhibitors might have therapeutic potential, cannot be excluded.

Amoxicillin↗