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Biomedical subjects

S Richardson

Publications and source records attributed to S Richardson.

At least 37 records · Page 2Linked to original sources
PubMed2001

High-performance anion-exchange chromatography-electrospray mass spectrometry for investigation of the substituent distribution in hydroxypropylated potato amylopectin starch.

The use of high-performance anion-exchange chromatography (HPAEC) with pulsed amperometric detection (PAD) coupled on-line with electrospray mass spectrometry (ESI-MS) for analysis of the substitution pattern in chemically modified starch, has been investigated. In order to characterise the distribution of substitution groups along the polymer chain, hydroxypropylated potato amylopectin starch (HPPAP) was subjected to enzymic hydrolysis, followed by analysis of the degradation products by HPAEC-PAD-MS. When using conventional chromatographic techniques for characterisation of enzymic hydrolysates, standard compounds are required for identification of the hydrolysis products. However, the on-line coupling with ESI-MS allowed identification of all products obtained, substituted as well as unsubstituted, and also of those compounds that co-eluted, without the need for standards. Further, HPAEC-PAD-MS was shown to be useful for analysis of the substitution pattern in modified starch; from results obtained it was suggested that the hydroxypropyl groups were homogeneously distributed in the amylopectin molecule. It was also shown that the starch hydrolysing enzymes were hindered by the hydroxypropyl groups and preferentially cleaved glucosidic linkages between unsubstituted glucose units.

Amylopectin↗
PubMed2001

Oropharyngeal candidiasis in patients with human immunodeficiency virus: correlation of clinical outcome with in vitro resistance, serum azole levels, and immunosuppression.

Azole-resistant thrush has emerged as a problem in people who are infected with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS), especially those who have low CD4 cell counts who have had a previous relapse of oral candidiasis, and in those who require long-term suppressive antifungal therapy. Because of the development of a standardized methodology for antifungal susceptibility testing and interpretive criteria for resistance testing, studies of the clinical predictive value of in vitro results are possible. In this study, 61% of organisms isolated from patients who were receiving azole therapy and who had clinically resistant thrush had minimal inhibitory concentration values that would classify the isolate as "resistant" or "susceptible dose dependent." In contrast, 86% of isolates from patients with thrush that was clinically responsive to an azole were classified in vitro as "susceptible" or "susceptible dose dependent." No resistant isolates were detected in samples obtained from asymptomatic control patients who were not exposed to azole drugs. Serum levels of azole and CD4 cell counts were also important parameters with regard to prediction of response. We conclude that in vivo and in vitro correlations compare favorably to studies of susceptibility testing in bacteria.

AIDS-Related Opportunistic Infections↗
PubMed2001

Casualization of the nursing workforce: a New Zealand perspective on an international phenomenon.

A discussion of the increased use of 'casual' nursing staff (those nurses employed on a casual or 'per diem' basis) is presented. Reference is made to related literature, together with consideration of the implications associated with this trend. This issue has international significance, with the increased use of casual staff being widely recognised. A New Zealand perspective is included, with the provision of nursing care at Christchurch Hospital presented to illustrate certain aspects of the discussion. The impact of changing health-care systems and increased emphasis on efficiency and accountability are identified. This change to workplace practice will inevitably affect nursing; possible future developments are considered.

Efficiency, Organizational↗
PubMed2001

Use of antenatal steroids to counteract the negative effects of tracheal occlusion in the fetal lamb model.

Tracheal occlusion (TO) in fetal lambs induces pulmonary hyperplasia but has negative effects on type II cells. The purpose of this study was to determine whether antenatal steroids could reverse the adverse effects of TO on lung maturation in fetal lambs. Sixteen time-dated pregnant ewes (term, 145 d) and 24 of their fetuses were divided into six groups: 1) TO at 117 d gestation; 2) TO at 117 d with a single maternal intramuscular injection of 0.5 mg/kg betamethasone 24 h before delivery; 3) TO at 117 d and release of the occlusion 2 d before delivery; 4) TO and release of the occlusion with maternal steroids; 5) unoperated controls without antenatal steroid treatment; and 6) unoperated controls, littermates of groups 1-4, treated with antenatal steroids. All fetuses were killed at 137 d gestation. Outcome measurements consisted of lung weight-to-body weight ratio; lung morphometry determined by mean terminal bronchial density; and assessment of type II pneumocytes by in situ hybridization to the mRNA of surfactant proteins B and C. Lung weight-to-body weight ratio and mean terminal bronchial density were significantly different among groups with TO and controls, indicating increased lung growth and structural maturation. The density of type II pneumocytes was markedly decreased by TO. Release 2 d before sacrifice significantly increased the density and surfactant activity of type II pneumocytes, but to levels still far from controls. Steroids alone had an effect similar to release. An additive effect was noted with steroids and 2-d release resulting in type II cell density comparable to controls. After fetal TO, a single maternal intramuscular dose of 0.5 mg/kg of betamethasone 24 h before delivery allows partial recuperation of the type II pneumocytes, an effect that is potentiated by 2-d release.

Animals↗
PubMed2001

Parental divorce during adolescence and adjustment in early adulthood.

The present study examined the impact of parental divorce during adolescence, interparental conflict, and intimacy with parents on young adult adjustment. One hundred sixty-seven undergraduate students (146 females, 21 males) completed a questionnaire regarding their psychosocial adjustment, their present relationships with their parents, the level of interparental conflict experienced during adolescence, and the marital status of their parents during adolescence. High levels of interparental conflict were found to be negatively associated with adjustment and current intimacy with parents. A poor relationship with both parents was negatively associated with several domains of psychosocial adjustment, while high intimacy with at least one parent was positively associated with adjustment. Intimacy with mother and with father were found to be the most important predictors of psychosocial adjustment. This investigation highlights the importance of maintaining a good parent-young adult relationship, particularly in divorced families. The findings indicate that future research should examine multiple family variables when assessing the impact of parental divorce or conflict on young adult adjustment.

Adaptation, Psychological↗
PubMed2000

Characterisation of the substituent distribution in hydroxypropylated potato amylopectin starch.

The distribution of substituents in hydroxypropylated potato amylopectin starch (amylose deficient) modified in a slurry of granular starch (HPPAPg) or in a polymer 'solution' of dissolved starch (HPPAPs), was investigated. The molar substitution (MS) was determined by three different methods: proton nuclear magnetic resonance (1H NMR) spectroscopy, gas-liquid chromatography (GLC) with mass spectrometry, and a colourimetric method. The MS values obtained by 1H NMR spectroscopy were higher than those obtained by GLC-mass spectrometry analysis and colourimetry. The relative ratio of 2-, 3-, and 6-substitution, as well as un-, mono-, and disubstitution in the anhydroglucose unit (AGU) were determined by GLC-mass spectrometry analysis. Results obtained showed no significant difference in molar distribution of hydroxypropyl groups in the AGU between the two derivatives. For analysis of the distribution pattern along the polymer chain, the starch derivatives were hydrolysed by enzymes with different selectivities. Debranching of the polymers indicated that more substituents were located in close vicinity to branching points in HPPAPg than in HPPAPs. Simultaneous alpha-amylase and amyloglucosidase hydrolysis of HPPAPg liberated more unsubstituted glucose units than the hydrolysis of HPPAPs, indicating a more heterogeneous distribution of substituents in HPPAPg.

Amylopectin↗
PubMed2000

Potent and selective nonpeptide inhibitors of caspases 3 and 7 inhibit apoptosis and maintain cell functionality.

Caspases have been strongly implicated to play an essential role in apoptosis. A critical question regarding the role(s) of these proteases is whether selective inhibition of an effector caspase(s) will prevent cell death. We have identified potent and selective non-peptide inhibitors of the effector caspases 3 and 7. The inhibition of apoptosis and maintenance of cell functionality with a caspase 3/7-selective inhibitor is demonstrated for the first time, and suggests that targeting these two caspases alone is sufficient for blocking apoptosis. Furthermore, an x-ray co-crystal structure of the complex between recombinant human caspase 3 and an isatin sulfonamide inhibitor has been solved to 2.8-A resolution. In contrast to previously reported peptide-based caspase inhibitors, the isatin sulfonamides derive their selectivity for caspases 3 and 7 by interacting primarily with the S(2) subsite, and do not bind in the caspase primary aspartic acid binding pocket (S(1)). These inhibitors blocked apoptosis in murine bone marrow neutrophils and human chondrocytes. Furthermore, in camptothecin-induced chondrocyte apoptosis, cell functionality as measured by type II collagen promoter activity is maintained, an activity considered essential for cartilage homeostasis. These data suggest that inhibiting chondrocyte cell death with a caspase 3/7-selective inhibitor may provide a novel therapeutic approach for the prevention and treatment of osteoarthritis, or other disease states characterized by excessive apoptosis.

Amino Acid Chloromethyl Ketones↗
PubMed2000

Biases in ecological studies: utility of including within-area distribution of confounders.

This paper is centred on studies commonly known as ecological studies, where one seeks to estimate risks from data aggregated on a geographical basis. The aggregated nature of the data creates difficulties for interpreting, at an individual level, any ecological association found, difficulties which are generically referred to as 'the ecological bias or fallacy'. Here, we address an important component of this bias related to the problem of misspecification in ecological studies. We consider how aggregated level dose-response relationships are derived from integrating individual level ones over the group, and how their correct specification requires, in general, knowledge of the within-group joint distribution of the relevant risk factors, which is rarely available. We discuss in detail the common situation where data on the proportion of persons exposed in each area to several dichotomous risk factors are available. We show that ecological regression estimates of the relative risk for each factor will be improved by including in the regression, besides the linear terms, cross-product terms of the marginal prevalences. Results from a simulation study are discussed and an example concerning the geographical analysis of lung cancer mortality in France is presented.

Adult↗
PubMed2000

Ecological analysis of digestive cancer mortality related to contamination by diarrhetic shellfish poisoning toxins along the coasts of France.

Shellfish consumers are exposed to the risk of diarrhea from, among other contaminants, algae that produce diarrhetic shellfish poisoning (DSP) toxins, such as Dinophysis spp. These illnesses have been effectively prevented since 1984, when a phycotoxin monitoring network was set up along the coasts of France. There is nonetheless concern that residual levels of okadaic acid, a known tumor promoter that is the main toxin present in French coastal waters, might increase the risk of cancer among regular shellfish consumers. To test this hypothesis, we conducted an ecological study linking digestive cancer mortality rates with a proxy measure of contamination by DSP toxins in 59 coastal areas. Observed and expected numbers of deaths (using national rates as the reference) were computed by sex, cause of death, and area for two time periods: 1984-1988 and 1989-1993. The level of contamination in each area was estimated by the total number of weeks since monitoring began that production was shut down because of DSP toxin contamination. Using both Poisson regressions and test for trends of standardized mortality ratios across four exposure categories, we found some evidence of associations for several digestive cancer sites (esophagus, stomach, colon, liver, and total digestive cancers for men; stomach and pancreatic cancers for women). Among men, the only statistically significant result that remained after taking possible confounding by alcohol use into account involved colon cancer. The conclusions provided by this analysis are very tentative; they need to be reproduced and interpreted in the light of additional information on the potential long-term effects of DSP toxins. In the absence of human data, they provide some indication of a possible association between exposure to DSP toxins and digestive cancers.

Adult↗
PubMed2000

Projection of cancer risks from the Japanese atomic bomb survivors to the England and Wales population taking into account uncertainty in risk parameters.

Generalized relative risk models, with adjustments to the relative risk for time after exposure and age at exposure and incorporating a linear-quadratic dose response, were fitted to the latest (Life Span Study Report 12) Japanese atomic bomb survivor cancer mortality data using Bayesian Markov Chain Monte Carlo methods, taking account of random errors in the DS86 dose estimates. The resulting uncertainty distributions in the relative risk model parameters were used to derive uncertainties in population cancer risks for a current UK population. Following an assumed administered dose of 1 Sv, leukaemia mortality risks were estimated to be 1.93x10(-2) Sv(-1) (95% CI 1.14, 3.38), or 0.44 years of life lost Sv(-1) (95% CI 0.22, 0.94). Following an assumed administered dose of 1 Sv, solid cancer mortality risks were calculated to be 10.36x10(-2) Sv(-1) (95% CI 8.41, 12.42), or 1.38 years of life lost Sv(-1) (95% CI 1.11, 1.68). In general, solid cancer risks were very similar to those predicted by classical likelihood-based methods; however, leukaemia risks were somewhat higher, by 10-35%, than those predicted by classical likelihood-based methods. This is so in both cases, irrespective of whether or not adjustments are made in these likelihood-based fits for the effects of measurement errors, and the discrepancy for leukaemia tends to be greater at higher doses. Overall, cancer risks predicted by Bayesian Markov Chain Monte Carlo methods are similar to those derived by classical likelihood-based methods and which form the basis of established estimates of radiation-induced cancer risk.

Bayes Theorem↗
PubMed2000

[Methodological problems in health-environment ecological studies].

Different approaches are used to study the effects of the environment on health. We restrict our discussion to observational studies at the aggregated level, the so-called ecological studies. We discuss several sources of bias for group-level studies and consider questions relating to the link between individual-level and group-level dose-effect relationship, the difference between group exposure and environmental exposure, and the influence of measurement error and variability in the exposure. Taking into consideration confounding factors in the analyses is another important item that is discussed. A final item concerns the necessity of studying the temporal direction of the effect, as well as assessing the existence of a potential threshold in the effect. As a broad conclusion, we can say that realistic quantification of uncertainty in dose-effect relationships is a delicate task that requires the systematic consideration of all sources of variability, as well as a transparent sensitivity analysis of the choices and hypotheses made during the statistical analysis.

Bias↗
PubMed2000

Distal procto-colitis and n-3 polyunsaturated fatty acids: the mechanism(s) of natural cytotoxicity inhibition.

BACKGROUND: Altered natural killer (NK) and lymphokine-activated killer (LAK) cell activities have been reported with ulcerative colitis (UC). Previously, we have shown that in patients with UC, the n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), specifically inhibit natural cytotoxicity with clinical improvement in disease activity. The aim of this study therefore was to evaluate the possible mechanism(s) involved in this inhibition, and in particular the alteration of production of interleukin 2 (IL2) and the arachidonic acid metabolite leukotriene B4 (LTB4), both known to modulate NK cell activity. MATERIALS AND METHODS: Each patient with procto-colitis received either fish oil extract (EPA 3.2 g, DHA 2.4 g; n = 9) or placebo (n = 9) daily for 6 months. Monthly assessment included disease activity using clinical and sigmoidoscopic scores. Peripheral blood mononuclear (PBMN) cells were isolated and NK cell cytotoxic activity in vitro was measured. Monthly serum samples were analysed for LTB4, IL2 and soluble IL2 receptors (sIL2R). RESULTS: The n-3 PUFAs group had significantly reduced NK cell activity, compared with the placebo group (P < 0.05, Mann-Whitney U-test). In the n-3 PUFA group, incubation of PBMN cells for 72 h with recombinant interleukin 2 (rIL2) reversed the NK inhibition. In patients with active proctocolitis, serum levels of LTB4 correlated positively with NK cell cytotoxicity (r = 0.873, P < 0.05, Kendall's correlation coefficient). After six months of n-3 PUFAs supplementation, serum levels of LTB4 were undetectable with concurrent significant reduction in NK cell cytotoxic activity. The latter was associated with significant reduction of serum IL2 and sIL2R levels (P < 0.05). CONCLUSION: This study has demonstrated both evidence of suppression of immune reactivity and concurrent reduction in disease activity in patients with proctocolitis receiving n-3 PUFAs supplementation. This may have important implications for therapy in patients with UC.

Cytotoxicity, Immunologic↗
PubMed2000

Modeling markers of disease progression by a hidden Markov process: application to characterizing CD4 cell decline.

Multistate models have been increasingly used to model natural history of many diseases as well as to characterize the follow-up of patients under varied clinical protocols. This modeling allows describing disease evolution, estimating the transition rates, and evaluating the therapy effects on progression. In many cases, the staging is defined on the basis of a discretization of the values of continuous markers (CD4 cell count for HIV application) that are subject to great variability due mainly to short time-scale noise (intraindividual variability) and measurement errors. This led us to formulate a Bayesian hierarchical model where, at a first level, a disease process (Markov model on the true states, which are unobserved) is introduced and, at a second level, the measurement process making the link between the true states and the observed marker values is modeled. This hierarchical formulation allows joint estimation of the parameters of both processes. Estimation of the quantities of interest is performed via stochastic algorithms of the family of Markov chain Monte Carlo methods. The flexibility of this approach is illustrated by analyzing the CD4 data on HIV patients of the Concorde clinical trial.

Algorithms↗
PubMed2000

A spiral phantom for IMRT and tomotherapy treatment delivery verification.

A solid water/cylindrical phantom is machined to create a spiral cavity for placing radiographic or radiochromatic film in a spiral configuration. This spiral phantom is used to sample, predict, and measure data in three-dimension subspace. The predicted data are obtained by projecting the patient plan data on the spiral phantom in the treatment planning software. The measured data are obtained by irradiating the spiral phantom (with film in the spiral cavity) as per the treatment plan. The predicted and measured data are converted to a two-dimensional matrix and plotted as a spiralogram. Comparison of these predicted and measured spiralograms provides a quantitative comparison and thus validation of treatment delivered as planned. The spiral phantom is a simple, cost-effective approach to sample 3D data from complexly shaped, intensity modulated or compensated multiple beams. A software script is being written to automate the entire process of projection, data sampling, and comparison. Design aspects and some examples of dose verification are presented. The usefulness of the spiral phantom for intensity modulated radiation therapy and dynamic field shaping are discussed.

Computer Simulation↗