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Biomedical subjects

K White

Publications and source records attributed to K White.

At least 19 recordsLinked to original sources

Influenza vaccination coverage among children aged 6-23 months - six immunization information system sentinel sites, United States, 2005-06 influenza season.

Beginning with the 2004-05 influenza season, the Advisory Committee on Immunization Practices (ACIP) recommended that all children aged 6-23 months receive influenza vaccinations annually. Other children recommended to receive influenza vaccinations include those aged 6 months-18 years who have certain high-risk medical conditions, those on chronic aspirin therapy, those who are household contacts of persons at high risk for influenza complications, and, since 2006, all children aged 24-59 months. Previously unvaccinated children aged <9 years need 2 doses administered at least 1 month apart to be considered fully vaccinated. This report assesses influenza vaccination coverage among children aged 6-23 months during the 2005-06 influenza season by using data from six immunization information system (IIS) sentinel sites. The findings demonstrate that vaccination coverage with 1 or more doses varied widely (range: 6.6% to 60.4%) among sites, with coverage increasing from the preceding influenza season in four of the six sites. However, <23% of children in five of the sites were fully vaccinated, underscoring the need for increased measures to improve the proportion of children who are fully vaccinated.

Humans↗

Saccades in presymptomatic and early stages of Huntington disease.

OBJECTIVE: To evaluate quantitative measures of eye movements as possible biomarkers in prediagnostic and early stages of Huntington disease (HD). METHODS: The study sample (n = 215) included individuals both at risk and recently diagnosed with HD. All participants completed a uniform clinical evaluation which included administration of the Unified Huntington's Disease Rating Scale (UHDRS) by a movement disorder neurologist and molecular testing to determine HD gene status. A high resolution, video-based eye tracking system was employed to quantify measures of eye movement (error rates, latencies, SD of latencies, velocities, and accuracies) during a computerized battery of saccadic and steady fixation tasks. RESULTS: Prediagnostic HD gene carriers and individuals with early HD demonstrated three types of significant abnormalities while performing memory guided and anti-saccade tasks: increased error rate, increased saccade latency, and increased variability of saccade latency. The eye movement abnormalities increased with advancing motor signs of HD. CONCLUSIONS: Abnormalities in eye movement measures are a sensitive biomarker in the prediagnostic and early stages of Huntington disease (HD). These measures may be more sensitive to prediagnostic changes in HD than the currently employed neurologic motor assessment.

Eye Movements↗

Genotoxic effect of copper on salivary gland polytene chromosomes of Chironomus riparius Meigen 1804 (Diptera, Chironomidae).

The genotoxic action of copper (Cu) on the polytene chromosomes of Chironomus riparius was investigated by analysing structural and functional chromosome aberrations of fourth instars larvae hatched from eggs subject to acute (48 h) exposure with three environmentally relevant concentrations of aqueous Cu (0.005, 0.01, 0.05 mg/l). A dose dependent relationship was observed between Cu concentration and frequency of chromosomal aberrations. A significantly higher frequency of functional alterations, specifically decondensed centromeres and telomeres, and reduction in activity of Balbiani rings, was observed in treated material compared to control. A comparison of breakpoints resulting from treatment with chromium and lead from earlier studies with those Cu-induced identified a series of chromosomal weak points particularly vulnerable to trace metals. We also show that the appearance of structural and functional chromosome aberrations are more sensitive indicators of acute Cu toxicity in chironomid larvae than changes in external morphology.

Animals↗

One woman's journey is a journey we all may share.

In recent years, there has been a growing awareness of the need to take account of the patient's own experience of illness. Although this is to be welcomed, it is also important to hear the stories of those most affected by the patient's illness, their partners, their families, their communities and those who care for them. 'On being both professional and human: one woman's journey' provides a powerful example of how narrative may assist clinicians to learn about communication, care, presence and the effect of illness and death on those left behind.

Attitude to Health↗

Safety and immunogenicity of New Zealand strain meningococcal serogroup B OMV vaccine in healthy adults: beginning of epidemic control.

As the first step towards control of a strain specific epidemic of meningococcal disease in New Zealand (NZ), this study, an observer-blind, randomised controlled trial in 75 healthy adults, evaluated safety and immunogenicity of two different dosages of a meningococcal group B vaccine administered in a three dose regime. The "tailor-made" outer membrane vesicle (OMV) vaccine (candidate vaccine) developed using a New Zealand meningococcal group B strain (B:4:P1.7b,4) was well tolerated with no vaccine related serious adverse events. Similar local and systemic reactions were observed in those receiving the New Zealand candidate vaccine and the control parent Norwegian vaccine (MenBvac). A four-fold rise in serum bactericidal antibodies (SBAb) against the vaccine strain 4-6 weeks after the third vaccination was achieved in 100% of New Zealand candidate vaccine 2,519 microg participants and in 87% of 50 microg participants. The safety and immunogenicity profile observed in this study of healthy adults enabled studies in children to be initiated using 25 microg dosage.

Adolescent↗

Perfluorochemicals: potential sources of and migration from food packaging.

Perfluorochemicals are widely used in the manufacturing and processing of a vast array of consumer goods, including electrical wiring, clothing, household and automotive products. Furthermore, relatively small quantities of perfluorochemicals are also used in the manufacturing of food-contact substances that represent potential sources of oral exposure to these chemicals. The most recognizable products to consumers are the uses of perfluorochemicals in non-stick coatings (polytetrafluoroethylene (PTFE)) for cookware and also their use in paper coatings for oil and moisture resistance. Recent epidemiology studies have demonstrated the presence of two particular perfluorochemicals, perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) in human serum at very low part per billion levels. These perfluorochemicals are biopersistent and are the subject of numerous studies investigating the many possible sources of human exposure. Among the various uses of these two chemicals, PFOS is a residual impurity in some paper coatings used for food contact and PFOA is a processing aid in the manufacture of PTFE used for many purposes including non-stick cookware. Little information is available on the types of perfluorochemicals that have the potential to migrate from perfluoro coatings into food. One obstacle to studying migration is the difficulty in measuring perfluorochemicals by routine conventional analytical techniques such as GC/MS or LC-UV. Many perfluorochemicals used in food-contact substances are not detectable by these conventional methods. As liquid chromatography-mass spectrometry (LC/MS) develops into a routine analytical technique, potential migrants from perfluoro coatings can be more easily characterized. In this paper, data will be presented on the types of perfluoro chemicals that are used in food packaging and cookware. Additionally, research will be presented on the migration or potential for migration of these chemicals into foods or food simulating liquids. Results from migration tests show mg kg(-1) amounts of perfluoro paper additives/coatings transfer to food oil. Analysis of PTFE cookware shows residual amounts of PFOA in the low microg kg(-1) range. PFOA is present in microwave popcorn bag paper at amounts as high as 300 microg kg(-1).

Caprylates↗

Fatal human rabies caused by European bat Lyssavirus type 2a infection in Scotland.

We wish to report the first recorded case of indigenous human rabies caused by a bat bite in the United Kingdom in 100 years. This instructive case report highlights a number of key lessons: first, bites from insectivorous bats indiginous to the United Kingdom can cause rabies in humans; second, rabies immunization is essential for bat-handlers, and postexposure treatment for rabies is essential for patients bitten by bats; third, patients able to give a history who present with acute flaccid paralysis and/or presumptive viral encephalitis should be asked if they have been bitten by bats, irrespective of travel history, or this history should be obtained from family or friends; fourth, antemortem diagnosis of bat rabies (EBLV type 2a infection) in humans is possible using RT-PCR.

Animals↗

Predictors of major bleeding in acute coronary syndromes: the Global Registry of Acute Coronary Events (GRACE).

AIMS: There have been no large observational studies attempting to identify predictors of major bleeding in patients with acute coronary syndromes (ACS), particularly from a multinational perspective. The objective of our study was thus to develop a prediction rule for the identification of patients with ACS at higher risk of major bleeding. METHODS AND RESULTS: Data from 24045 patients from the Global Registry of Acute Coronary Events (GRACE) were analysed. Factors associated with major bleeding were identified using logistic regression analysis. Predictive models were developed for the overall patient population and for subgroups of patients with ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI) and unstable angina. The overall incidence of major bleeding was 3.9% (4.8% in patients with STEMI, 4.7% in patients with NSTEMI and 2.3% in patients with unstable angina). Advanced age, female sex, history of bleeding, and renal insufficiency were independently associated with a higher risk of bleeding (P<0.01). The association remained after adjustment for hospital therapies and performance of invasive procedures. After adjustment for a variety of potential confounders, major bleeding was significantly associated with an increased risk of hospital death (adjusted odds ratio 1.64, 95% confidence interval 1.18, 2.28). CONCLUSIONS: In routine clinical practice, major bleeding is a relatively frequent non-cardiac complication of contemporary therapy for ACS and it is associated with a poor hospital prognosis. Simple baseline demographic and clinical characteristics identify patients at increased risk of major bleeding.

Adult↗

Histological, immunohistochemical and morphometric changes in lung tissue in juvenile mice experimentally exposed to Stachybotrys chartarum spores.

Stachybotrys chartarum is an important toxigenic fungus often associated with chronically wet cellulose-based building materials. The purpose of this study was to evaluate some histological, immunohistochemical and morphometric changes in mouse lung tissues exposed intratracheally to either 50 microl of 1.4 x 10(6) S. chartarum spores (< or = 35 ng toxin/kg BW), isosatratoxin-F (35 ng/kg BW), 50 microl of 1.4 x 10(6) Cladosporium cladosporioides spores, or 50 microl saline. Exposure of lung tissues to S. chartarum or C. cladosporioides spores resulted in granuloma formation at the sites of spore impaction. Some of the lung tissues impacted by S. chartarum spores also showed erythrocyte accumulation in the alveolar air space, dilated capillaries engorged with erythrocytes, and hemosiderin accumulation at spore impaction sites, which were features not noted in the C. cladosporioides-spore treated animals. Immunohistochemistry revealed reduced collagen IV distribution in lung granulomas in S. chartarum-treated animals especially at 48 and 72 hr post-exposure compared to that in lungs of mice with C. cladosporioides-spore induced granulomas. Quantitative analysis of pooled S. chartarum and C. cladosporioides spore impacted lungs revealed significant depression (P < 0.05) of alveolar air space from 71.4 +/- 6.1% in untreated animals to 56.04 +/- 6.1% in the S. chartarum- and 60.24 +/- 5.5% in the C. cladosporioides-spore treated animals. It also revealed that alveolus air space in S. chartarum treated animals declined significantly from 63.74 +/- 3.1% at 12 hr post-exposure to 42.94 +/- 7.9% at 72 hr post-exposure and was increased to 54.84 +/- 5.2% at 96 hr post-exposure. Alveolus air space in C. cladosporioides treated animals also decreased significantly from 64.84 +/- 7.1% at 12 hr exposure to 54.94 +/- 5.4% at 48 hr post-exposure and was increased to 64.64 +/- 10.1% at 96 hr post-exposure. It also revealed significant (P < 0.05) alveolar accumulation of erythrocytes from 1.24 +/- 1.4% in the untreated animals to 3.44 +/- 1.5% in the pooled S. chartarum spore treated animals. Erythrocyte abundance in S. chartarum treated animals increased significantly (P < 0.001) from 2.14 +/- 1.7% at 12 hr post-exposure to 5.54 +/- 1.5% at 72 hr and 4.94 +/- 1.4% at 96 hr post-exposure. These results further reveal that exposure to S. chartarum spores elicit tissue responses in vivo significantly different from those associated with exposure to pure trichothecene toxin and to spores of a non-toxigenic fungus.

Animals↗

The hidden side of nursing: why caring for patients with malignant malodorous wounds is so difficult.

OBJECTIVE: This cross-sectional qualitative study used semi-structured telephone interviews with palliative care nurses working in urban and rural settings in Australia to explore their experiences of dealing with patients with malignant, often malodorous, wounds. METHOD: This paper was the second phase of a research project examining the care of patients with malignant wounds. Of 71 palliative care nurses in New South Wales invited to participate, 26 took part, 17 of them working in community positions. The data from the telephone interviews were transcribed and analysed, using content analysis, and coded for themes relating to the nurses' experiences of caring for this patient group. RESULTS: Nurses working in this setting strove to do the best for patients and their families under circumstances that are emotionally and physically difficult. Some of them suffered personal distress as a consequence. Patient isolation and altered body image are significant challenges for these nurses. CONCLUSION: The nature of the work these nurses do, in particular the fact that they are dealing with cancers, tends to push them into literal and practical silence. But the researchers question whether this is always the best option. They ask if hiding feelings could be bad for nurses and patients alike. In qualitative research it is not appropriate to generalize the results, although lessons can be learnt from the experience of this group.

Adaptation, Psychological↗

Renal cell carcinoma and occupational exposure to chemicals in Canada.

This study assesses the effect of occupational exposure to specific chemicals on the risk of renal cell carcinoma in Canada. Mailed questionnaires were used to obtain data on 1279 (691 male and 588 female) newly diagnosed, histologically confirmed renal cell carcinoma cases and 5370 population controls in eight Canadian provinces, between 1994 and 1997. Data were collected on socio-economic status, smoking habit, alcohol use, diet, residential and occupational histories, and years of exposure to any of 17 chemicals. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived using unconditional logistic regression. The study found an increased risk of renal cell carcinoma in males only, which was associated with occupational exposure to benzene; benzidine; coal tar, soot, pitch, creosote or asphalt; herbicides; mineral, cutting or lubricating oil; mustard gas; pesticides; and vinyl chloride. Compared with no exposure to the specific chemical, the adjusted ORs were 1.8 (95% CI = 1.2-2.6), 2.1 (1.3-3.6), 1.4 (1.1-1.8), 1.6 (1.3-2.0), 1.3 (1.1-1.7), 4.6 (1.7-12.5), 1.8 (1.4-2.3) and 2.0 (1.2-3.3), respectively; an elevated risk was also associated with exposure to cadmium salts and isopropyl oil. The risk of renal cell carcinoma increased with duration of exposure to benzene, benzidine, cadmium, herbicides and vinyl chloride. Very few females were exposed to specific chemicals in this study; further research is needed to clarify the association between occupational exposure to chemicals and renal cell carcinoma in females.

Adult↗

Microanatomical changes in alveolar type II cells in juvenile mice intratracheally exposed to Stachybotrys chartarum spores and toxin.

Stachybotrys chartarum is an important environmental fungus. We have shown recently that alveolar type II cells are sensitive to exposure to Stachybotrys chartarum spores and to the trichothecene, isosatratoxin-F, both in vitro and in vivo, in a juvenile mouse model. This sensitivity is manifest as significant changes in the composition and normal metabolic processing of pulmonary surfactant. This study evaluated the effects of a single intratracheal exposure of S. chartarum spores and toxin on ultrastructure and dimensions of alveolar type II cells from juvenile mice. This was to determine whether there are concurrent morphological and dimensional changes in the alveolar type II cell that reflect the metabolic alterations in pulmonary surfactant that we observed in the treated mice. Marked ultrastructural changes were associated with alveolar type II cells in both S. chartarum and isosatratoxin-F treated animals compared to untreated, saline, and Cladosporium cladosporioides spore treated animals. These ultrastructural changes included condensed mitochondria with separated cristae, scattered chromatin and poorly defined nucleolus, cytoplasmic rarefaction, and distended lamellar bodies with irregularly arranged lamellae. Point count stereological analysis revealed a significant increase (p < 0.05) in lamellar body volume density in S. chartarum and isosatratoxin-treated animals after 48 h exposure. Mitochondria volume density was significantly lower in the isosatratoxin-F (48 h exposure) and S. chartarum treated (24 and 48 h exposure) animals compared to those in the other treatment groups. These results reveal that exposure to S. chartarum spores and toxin elicit cellular responses in vivo differently from those associated with exposure to spores of a nontoxigenic mold species. They also indicate that accumulation of newly secreted pulmonary surfactant in the alveolar space of S. chartarum and isosatratoxin-F treated animals might be a consequence of cellular trauma resulting in lamellar body volume density changes leading to increased release of pulmonary surfactant into the alveolar space.

Animals↗

Active and passive smoking and the risk of stomach cancer, by subsite, in Canada.

This study assessed the influence of active and passive smoking on the risk of stomach cancer by subsite. Mailed questionnaires were used to obtain information on 1171 newly diagnosed histologically confirmed stomach cancer cases and 2207 population controls between 1994 and 1997 in eight Canadian provinces. Data were collected on socio-economic status, lifestyle and passive smoking status. Odds ratios (OR) and 95% confidence intervals (95% CI) were derived by logistic regression. Compared with those who had never smoked, there was strongly increased risk for ex- and current smokers among subjects with cardial stomach cancer. For men with cardial cancer, the adjusted ORs were 1.9 (95% CI 1.2-3.0) and 2.6 (95% CI 1.6-4.3) for ex-smokers and current smokers, respectively, with a similar pattern among women. Among men, the adjusted ORs were lower for subsites of stomach cancer other than cardia. These findings suggest that active and passive smoking may play an important role in the development of cardial stomach cancer.

Adult↗

Enhancing the effectiveness of tobacco package warning labels: a social psychological perspective.

OBJECTIVE: To outline social psychological principles that could influence the psychosocial and behavioural effects of tobacco warning labels, and to inform the development of more effective tobacco warning labels. DATA SOURCES: PsycInfo and Medline literature searches and expert guided selection of principles and theories in social psychology and of tobacco warning labels, including articles, books, and reports. CONCLUSIONS: Tobacco warning labels represent a potentially effective method of influencing attitudes and behaviours. This review describes social psychological principles that could be used to guide the creation of more effective warning labels. The potential value of incorporating warning labels into a broader public health education campaign is discussed, and directions for future research are suggested.

Consumer Product Safety↗

Identification of a novel retina-specific gene located in a subtelomeric region with polymorphic distribution among multiple human chromosomes.

The human retina is comprised of a large number of cell types with highly specialized functions that depend on the action of countless genes, many of which are exclusively expressed in the retina. We have isolated a novel retinal gene, termed F379. The transcript was initially identified as a cluster of ESTs derived predominantly from retinal cDNA libraries and its retinal transcription confirmed by Northern blot and RT-PCR. Screening of retinal cDNA libraries yielded four clones that were assembled into a 1188 bp consensus sequence. The putative open reading frame includes an unusual configuration of Alu and MIR repeats and encodes a putative 85 aa peptide with no significant homology to any known protein sequence outside of the Alu and MIR elements. Comparison with genomic sequence determined that F379 consists of three exons and maps to multiple locations throughout the genome, a finding confirmed by PCR screening of a somatic cell hybrid mapping panel. F379 appears to be contained within a region of subtelomeric DNA that is duplicated in a polymorphic distribution to multiple chromosomes. Comparison of interchromosomal sequence variation with the sequences of expressed transcripts suggests that the gene is transcribed in the human retina from at least four different chromosomes.

Amino Acid Sequence↗

The neuron-specific RNA-binding protein ELAV regulates neuroglian alternative splicing in neurons and binds directly to its pre-mRNA.

Drosophila melanogaster neural-specific protein, ELAV, has been shown to regulate the neural-specific splicing of three genes: neuroglian (nrg), erect wing, and armadillo. Alternative splicing of the nrg transcript involves alternative inclusion of a 3'-terminal exon. Here, using a minigene reporter, we show that the nrg alternatively spliced intron (nASI) has all the determinants required to recreate proper neural-specific RNA processing seen with the endogenous nrg transcript, including regulation by ELAV. An in vitro UV cross-linking assay revealed that ELAV from nuclear extracts cross-links to four distinct sites along the 3200 nucleotide long nASI; one EXS is positioned at the polypyrimidine tract of the default 3' splice site. ELAV cross-linking sites (EXSs) have in common long tracts of (U)-rich sequence rather than a precise consensus; moreover, each tract has at least two 8/10U elements; their importance is validated by mutant transgene reporter analysis. Further, we propose criteria for ELAV target sequence recognition based on the four EXSs, sites within the nASI that are (U) rich but do not cross-link with ELAV, and predicted EXSs from a phylogenetic comparison with Drosophila virilis nASI. These results suggest that ELAV regulates nrg alternative splicing by direct interaction with the nASI.

Alternative Splicing↗

Design, synthesis, and biological evaluation of analogues of the antitumor agent, 2-(4-[(7-chloro-2-quinoxalinyl)oxy]phenoxy)propionic acid (XK469).

2-(4-[(7-Chloro-2-quinoxalinyl)oxy]phenoxy)propionic acid (XK469) is among the most highly and broadly active antitumor agents to have been evaluated in our laboratories and is currently scheduled to enter clinical trials in 2001. The mechanism or mechanisms of action of XK469 remain to be elaborated. Accordingly, an effort was initiated to establish a pharmacophore hypothesis to delineate the requirements of the active site, via a comprehensive program of synthesis of analogues of XK469 and evaluation of the effects of structural modification(s) on solid tumor activity. The strategy formulated chose to dissect the two-dimensional parent structure into three regions-I, ring A of quinoxaline; II, the hydroquinone connector linkage; and III, the lactic acid moiety-to determine the resultant in vitro and in vivo effects of chemical alterations in each region. Neither the A-ring unsubstituted nor the B-ring 3-chloro-regioisomer of XK469 showed antitumor activity. The modulating antitumor effect(s) of substituents of differing electronegativities, located at the several sites comprising the A-ring of region I, were next ascertained. Thus, a halogen substituent, located at the 7-position of a 2-(4-[(2-quinoxalinyl)oxy]phenoxy)propionic acid, generated the most highly and broadly active antitumor agents. A methyl, methoxy, or an azido substituent at this site generated a much less active structure, whereas 5-, 6-, 8-chloro-, 6-, 7-nitro, and 7-amino derivatives all proved to be essentially inactive. When the connector linkage (region II) of 1 was changed from that of a hydroquinone to either a resorcinol or a catechol derivative, all antitumor activity was lost. Of the carboxylic acid derivatives of XK469 (region III), i.e., CONH2, CONHCH3, CON(CH3)2, CONHOH, CONHNH2, CN, or CN4H (tetrazole), only the monomethyl- and N,N-dimethylamides proved to be active.

Animals↗