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Biomedical subjects

K Mitchell

Publications and source records attributed to K Mitchell.

At least 19 recordsLinked to original sources
PubMed2006

The sand seas of Titan: Cassini RADAR observations of longitudinal dunes.

The most recent Cassini RADAR images of Titan show widespread regions (up to 1500 kilometers by 200 kilometers) of near-parallel radar-dark linear features that appear to be seas of longitudinal dunes similar to those seen in the Namib desert on Earth. The Ku-band (2.17-centimeter wavelength) images show approximately 100-meter ridges consistent with duneforms and reveal flow interactions with underlying hills. The distribution and orientation of the dunes support a model of fluctuating surface winds of approximately 0.5 meter per second resulting from the combination of an eastward flow with a variable tidal wind. The existence of dunes also requires geological processes that create sand-sized (100- to 300-micrometer) particulates and a lack of persistent equatorial surface liquids to act as sand traps.

Extraterrestrial Environment↗
PubMed2004

Physician commitment in end of life care--perspectives from New Zealand and the Netherlands.

A social constructionist approach is taken to analyse the accounts of experiences of doctors who have provided end of life care, comprising five Dutch doctors and six New Zealand doctors who had not provided physician-assisted death, and five Dutch doctors who had. A core theme of 'commitment' to the patient crossed all interviews and when a request for assisted death was received this theme altered and evolved differently between the groups. All respondents reacted by exploring reasons for the request and offering palliative care. When the request persisted, those who had provided euthanasia entered into a 'contractual commitment', constructing another "vulnerable" self in the negotiations that invited the sympathy of the hearer. This evolved to 'sacrificial commitment' when the physician provided euthanasia despite negative personal psychological effects. Constructing a self who is willing to sacrifice personal comfort to relieve the suffering of another is useful in silencing criticism of actions. The two groups who had not provided euthanasia, intensified their efforts to find an alternative to assisted death in a 'pledged commitment' to the patient, constructing themselves as deeply committed to the patient in an intimate struggle to meet his/her need. While New Zealand doctors denied that euthanasia had ever been an option, some Dutch doctors evolved their commitment to 'potential sacrificial commitment', constructing an open-minded and accepting self, willing to consider euthanasia despite fears of negative personal consequences. The construction of alternative 'selves' in accounts is useful in inviting sympathy and silencing potential criticism of actions that may be construed negatively (because the patient was assisted to die, or because assistance to die was refused).

Altruism↗
PubMed2003

Childhood smoking: the research, clinical and theoretical imperative for nursing action.

BACKGROUND: Tobacco smoking is a major international health issue which nurses are ideally positioned to address. Childhood represents a critical period for intervention to prevent/reduce smoking. During childhood, the majority of smokers first experiment with smoking, are initiated into the smoking subculture and become addicted to tobacco. Children are highly susceptible to smoking as a result of developmental factors, which promote or facilitate high-risk behaviours, limited coping skills, limited defences and inadequate legal protection against youth-focused marketing of tobacco. AIM: This paper is intended to sensitize nurses to the magnitude of childhood smoking as an international health problem and to familiarize them with current intervention approaches and care issues pertinent to child and adolescent populations. METHOD: An extensive literature review was conducted to determine the impact of childhood smoking at the personal and community level, characteristics of child smokers, the processes associated with smoking cessation, intervention approaches and intervention models for use by nurses across the spectrum of clinical settings. FINDINGS: Evidence exists that behaviourally based interventions by nurses for smoking prevention/cessation are effective with children. Key components of effective behaviourally based antismoking approaches for smokers include addressing self-efficacy to quit, providing social support, resisting temptation to smoke and discussing issues related to relapse and relapse prevention. For all children, the reinforcement of non-smoking behaviour is essential. Intervention models, which can be incorporated into routine clinical care of individual children or with groups, emphasize the importance of parental involvement, routine screening for tobacco use and provision of a clear message that smoking and tobacco use is unhealthy.

Child↗
PubMed2003

Clinical and psychological outcome from a randomized controlled trial of patient-initiated direct-access hospital follow-up for rheumatoid arthritis extended to 4 years.

BACKGROUND: Patients with rheumatoid arthritis (RA) are traditionally seen regularly as out-patients, irrespective of whether it is appropriate or timely to see them. A randomized controlled trial has shown that over 2 yr, seeing patients only when they or their general practitioner (GP) request a review saves time and resources and is more convenient. This study aimed to assess clinical and psychological outcomes when the trial was extended to 4 yr. METHOD: A total of 209 patients were randomized into either 'routine review' (control) or 'no routine follow-up' but access to rapid review on request (direct access). Clinical and psychological status and patient satisfaction and confidence were reviewed after 24 and 48 months. RESULTS: Mean age at entry was 56 yr and mean disease duration 11 yr, and 134 patients remained in the study after 48 months. There were no differences between the groups, nor between those who completed the study and those who did not. There were no major differences in clinical or psychological status between the groups at 24 or 48 months. However, self-efficacy for function was stronger at 48 months for direct access patients (mean 64.0 vs 52.0, P=0.005), as was self-efficacy for other symptoms (mean 67.8 vs 59.3, P=0.009). Satisfaction at 48 months was increased in direct access compared with control (mean 8.7 vs 7.6, P=0.01) as was confidence in the system (8.9 vs 7.6, P<0.01). CONCLUSION: It is effective for patients with rheumatoid arthritis to have no regular follow-up, provided they have access to rapid review when they or their GP request it. Patients using a self-referral system of care had higher self-efficacy and greater satisfaction and confidence than those using the traditional system.

Adult↗
PubMed2002

Structural implications of placing cationic residues at either the NH2- or COOH-terminus in a pore-forming synthetic peptide.

Restoration of chloride conductance via introduction of an anion-selective pore, formed by a channel-forming peptide, has been hypothesized as a novel treatment modality for patients with cystic fibrosis. Delivery of these peptides from an aqueous environment in the absence of organic solvents is paramount. M2GlyR peptides, designed based on the glycine receptor, insert into lipid bilayers and polarized epithelial cells and assemble spontaneously into chloride-conducting pores. Addition of 4 lysine residues to either terminus increases the solubility of M2GlyR peptides. Both orientations of the helix within the membrane form an anion-selective pore, however, differences in solubility, associations and channel-forming activity are observed. To determine how the positioning of the lysine residues affects these properties, structural characteristics of the lysyl-modified peptides were explored utilizing chemical cross-linking, NMR and molecular modeling. Initial model structures of the a-helical peptides predict that lysine residues at the COOH-terminus form a capping structure by folding back to form hydrogen bonds with backbone carbonyl groups and hydroxyl side chains of residues in the helical segment of the peptide. In contrast, lysine residues at the NH2-terminus form fewer H-bonds and extend away from the helical backbone. Results from NMR and chemical cross-linking support the model structures. The C-cap formed by H-bonding of lysine residues is likely to account for the different biophysical properties observed between NH2- and COOH-terminal-modified M2GlyR peptides.

Animals↗
PubMed2002

In vitro toxicity of 7H-dibenzo[c,g]carbazole in human liver cell lines.

7H-Dibenzo[c,g]carbazole (DBC) is a model N-heterocyclic aromatic compound (NHA) which is both a hepatotoxin and hepatocarcinogen in rodents. The focus of this investigation was to determine whether human liver cell lines display differential sensitivities to DBC-induced toxicity. Treatment of cell lines with increasing DBC concentrations produced apoptosis only in HepG2 cells. Although DBC inhibited the clonogenic growth of all cell lines at high concentrations, only the survival of HepG2 cells was reduced at lower concentrations. DBC inhibited DNA synthesis in two (HepG2, HLF) of the three cell lines at lower concentrations and was effective only at a high concentration in Mahlavu cells. Differences in DBC uptake were not observed in any of the cell lines, suggesting that bioavailability was not a limiting factor. DBC-DNA adducts were not detected in HLF or Mahlavu cells at either low or high concentrations of DBC. Consistent with the DNA adduct data, RP-HPLC analysis indicated that DBC was metabolized to a lesser degree in the HLF and Mahlavu cells. These results suggest that human liver cell lines differ markedly in the ability to metabolize DBC to toxic species and that DBC-induced apoptosis is only observed in cells that produce detectable metabolites and DBC-DNA adducts.

Apoptosis↗
PubMed2002

Giardia lamblia disrupts tight junctional ZO-1 and increases permeability in non-transformed human small intestinal epithelial monolayers: effects of epidermal growth factor.

In order to improve our understanding of the host cell-parasite interactions in giardiasis, this study assessed the effects of Giardia lamblia on epithelial permeability and tight junctional ZO-1, determined whether epidermal growth factor (EGF) may affect Giardia-induced epithelial injury, and evaluated if EGF modulates epithelial colonization by live G. lamblia trophozoites. Permeability was assessed in assays of trans-epithelial fluxes of FITC-dextran, and ZO-1 integrity was characterized by confocal laser immunofluorescence microscopy in confluent epithelial cell monolayers. G. lamblia significantly increased paracellular permeability and disrupted tight-junctional ZO-1 of a novel non-transformed human small intestinal epithelial cell line (SCBN). Pre-treatment with EGF prevented the development of these abnormalities and significantly inhibited attachment of live trophozoites to the enterocytes, independently of a direct microbiocidal action. These findings demonstrate that G. lamblia may cause intestinal pathophysiology by disrupting tight junctional ZO-1 and increasing epithelial permeability. Apical administration of EGF prevents these abnormalities, and reduces epithelial colonization by the live parasites.

Animals↗
PubMed2002

Triple cycle audit of primary retinal detachment surgery.

PURPOSE: To determine the effect of increasing subspecialisation on the results of retinal detachment surgery in one city. METHODS: Three audit cycles over a 10-year period when major subspecialisation and organisational changes were occurring. Retrospective case note reviews of all primary surgery for rhegmatogenous retinal detachments in each of the audit periods. Statistical analyses used contingency table/chi-square methods for comparing all three audits and Fisher's exact test/mean odds ratio with 95% confidence intervals (CIs) for the Audit 1 vs Audit 3 comparison. RESULTS: A marked improvement in success rates occurred: primary reattachment rose from 67% in Audit 1 to 87% in Audit 3 (P = 0.0004), and final success from 84% to 97% (P = 0.0003). There was a dramatic change in operative techniques over the same period: the percentage of vitrectomies increased from 1.5% in Audit 1 to 48% in Audit 3, while that of 'open' conventional procedures decreased from 78% to 32%. However, the improvement in anatomical success was not mirrored by an increase in the percentage of patients with 6/12 or better visual acuity postoperatively (55% in Audit 1, 49% in Audit 3; P = 0.34, mean odds ratio = 0.78; 95% CI 0.48-1.2). The percentage of patients with 6/18-6/36 post op visual acuity did increase in Audit 3 (18% in Audit 1; 29% in Audit 3; P = 0.03, mean odds ratio = 1.9; CI 1.1-3.3), and the percentage with 6/60 or worse decreased (27% in Audit 1, 20% in Audit 3; P = 0.26, mean odds ratio = 0.71; CI 0.40-1.2). CONCLUSIONS: With increased subspecialisation there has been an increase in anatomical success, but the goal of 100% reattachment is still not being attained. There remains scope for further improvement in anatomical and functional outcomes.

England↗
PubMed2002

Specificity of 14-3-3 isoform dimer interactions and phosphorylation.

Proteins that interact with 14-3-3 isoforms are involved in regulation of the cell cycle, intracellular trafficking/targeting, signal transduction, cytoskeletal structure and transcription. Recent novel roles for 14-3-3 isoforms include nuclear trafficking the direct interaction with cruciform DNA and with a number of receptors, small G-proteins and their regulators. Recent findings also show that the mechanism of interaction is also more complex than the initial finding of the novel phosphoserine/threonine motif. Non-phosphorylated binding motifs that can also be of high affinity may show a more isoform-dependent interaction and binding of a protein through two distinct binding motifs to a dimeric 14-3-3 may also be essential for full interaction. Phosphorylation of specific 14-3-3 isoforms can also regulate interactions. In many cases, they show a distinct preference for a particular isoform(s) of 14-3-3. A specific repertoire of dimer formation may influence which of the 14-3-3-interacting proteins could be brought together. Mammalian and yeast 14-3-3 isoforms show a preference for dimerization with specific partners in vivo.

14-3-3 Proteins↗
PubMed2002

Jamaica cancer mortality statistics, 1999.

A total of 2697 cancer-related deaths were documented among Jamaicans for the year 1999, accounting for 17.7% of all deaths. Males accounted for 1466 and females for 1231. The age-adjusted cancer mortality rate was 171.7 per 100,000 for males, 122.0 per 100,000 for females and 140.5 per 100,000 for the total population. Leading cancer mortality sites for males were prostate, lung and stomach and in females, breast, cervix uteri and large bowel. Most deaths were recorded in the 55-64 and 65-74 year-age groups. Despite well-established cervical cancer screening programmes, the calculated mortality rate for cancer of the cervix uteri in Jamaican females (15.8 per 100,000) is approximately two and a half times that seen in African-American females.

Adult↗
PubMed2001

Preconditioning with cortical spreading depression does not upregulate Cu/Zn-SOD or Mn-SOD in the cerebral cortex of rats.

Previous studies have demonstrated that preconditioning the brain with cortical spreading depression (CSD) induces tolerance to a subsequent episode of ischemia. In other models of preconditioning, induction of ischemic tolerance has been associated with increased expression of the antioxidant enzyme, superoxide dismutase (SOD). The objective of the present study was to determine whether CSD upregulates Cu/Zn-SOD or Mn-SOD. CSD was induced in one hemisphere by applying 2 M KCl to the frontal cortex in Wistar rats. After 2 or 24 h of recovery, Cu/Zn-SOD and Mn-SOD mRNA levels were determined in both hemispheres using Northern blot analysis. In separate rats, Cu/Zn-SOD and Mn-SOD protein levels were determined 24 and 72 h after CSD using Western blot analysis. In addition, total SOD, Cu/Zn-SOD and Mn-SOD enzymatic activities were measured 24 and 72 h after CSD using spectrophotometric and zymographic assays. At the times investigated, no significant differences in mRNA or protein levels for Cu/Zn-SOD or Mn-SOD were observed between the ipsilateral and contralateral cortex. Further, there were no significant differences in Cu/Zn-SOD or Mn-SOD enzymatic activities between the two hemispheres at 24 or 72 h after CSD. In addition, CSD did not alter the activities of Cu/Zn-SOD or Mn-SOD in either hemisphere, relative to those in unoperated animals. Taken together, these results fail to support the hypothesis that CSD-induced tolerance is mediated through the upregulation of Cu/Zn-SOD or Mn-SOD.

Animals↗
PubMed2001

New layered materials: syntheses, structures, and optical and magnetic properties of CsGdZnSe3, CsZrCuSe3, CsUCuSe3, and BaGdCuSe3.

Four new quaternary selenides CsGdZnSe3, CsZrCuSe3, CsUCuSe3, and BaGdCuSe3 have been synthesized with the use of traditional high-temperature solid-state experimental methods. These compounds are isostructural with KZrCuS3, crystallizing with four formula units in the orthorhombic space group Cmcm. Cell constants (A) at 153 K are CsGdZnSe3 4.1684(7), 15.765(3), 11.0089(18); CsZrCuSe3 3.903(2), 15.841(10), 10.215(6); CsUCuSe3 4.1443(7), 15.786(3), 10.7188(18); and BaGdCuSe3 4.1839(6), 13.8935(19), 10.6692(15). The structure of these ALnMSe3 compounds (A = Cs, Ba; Ln = Zr, Gd, U; M = Cu, Zn) is composed of 2 to infinity [LnMSe3(n-)] (n = 1, 2) layers separated by A atoms. The Ln atom is octahedrally coordinated to six Se atoms, the M atom is tetrahedrally coordinated to four Se atoms, and the A atom is coordinated to a bicapped trigonal prism of eight Se atoms. Because there are no Se-Se bonds in the structure, the oxidation state of A is 1+ (Cs) or 2+ (Ba), that of Ln is 3+ (Gd) or 4+ (Zr, U), and that of M is 1+ (Cu) or 2+ (Zn). CsGdZnSe3 and BaGdCuSe3, which are paramagnetic, obey the Curie-Weiss law and have effective magnetic moments of 7.87(6) and 7.85(5) muB for Gd(3+), in good agreement with the theoretical value of 7.94 muB. Optical transitions at 1.88 and 2.92 eV for CsGdZnSe3 and 1.96 eV for BaGdCuSe3 were deduced from diffuse reflectance spectra.

Journal Article↗
PubMed2001

Water-soluble HPMA copolymer-wortmannin conjugate retains phosphoinositide 3-kinase inhibitory activity in vitro and in vivo.

Phosphoinositide kinases and ATM-related genes play a central role in many physiological processes. Activation of phosphoinositide 3-kinase (PI 3-kinase) is essential for signal transduction by many growth factors and oncogenes and may contribute to tumor progression. In the nanomolar range, Wortmannin (WM), a fungal metabolite, is a potent inhibitor of type I PI 3-kinase; it covalently modifies its catalytic subunit. Because WM is soluble only in organic solvents and unstable in water, there are difficulties in its use in vivo. To generate a water-soluble WM derivative, we used a conjugate of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer and 11-O-desacetylwortmannin (DAWM), which has a slightly lower inhibitory activity than WM. We covalently attached DAWM to HPMA copolymer containing oligopeptide (GFLG) side-chains. The final product had an estimated molecular mass of 20 kDa and contained 2 wt.% of DAWM. The HPMA copolymer (PHPMA)-DAWM conjugate inhibited type I PI 3-kinase activity in vitro and growth factor-stimulated activation of Akt in vivo; it possessed approximately 50% of the inhibitory activity of DMSO solubilized WM. The specificity and stability of the PHPMA-DAWM conjugate is currently under investigation. The new water-soluble form of WM may be useful in investigations of the role of PI 3-kinase in tumor progression and other cellular biological functions in vivo.

Androstadienes↗
PubMed2001

Coexpression of granulocyte colony stimulating factor and its receptor in primary ovarian carcinomas.

Immunohistochemistry was used to determine the expression of granulocyte colony-stimulating factor (G-CSF) and its receptor (G-CSFR) in primary ovarian carcinomas. The expression of G-CSFR was observed in the malignant cells of each of the 46 primary carcinomas examined; G-CSF was coexpressed in both the malignant epithelial cells and the stroma of 56.5% of the specimens. Thus the majority of ovarian carcinomas harbor both potential autocrine and paracrine G-CSF axes. In 37% of the samples, G-CSF was expressed only within stromal cells, suggesting that only a potential paracrine system is in place. In a preliminary, retrospective, evaluation, the survival of patients whose tumors expressed only the apparent paracrine loop was significantly worse than patients whose tumors expressed both potential autocrine and paracrine G-CSF-based regulatory loops (14.5 vs. 42.5 months, respectively). Studies on the potential function of G-CSF were performed using the G-CSFR-expressing OVCAR-3 ovarian carcinoma line. As a single agent, rhG-CSF failed to stimulate [3H]-thymidine incorporation in these cells, but enhanced the mitogenic action of epidermal growth factor (EGF) in a dose-dependent manner. Thus, potential autocrine and/or paracrine loops involving G-CSF and its receptor occur in over 90% of primary ovarian carcinomas, and may act to modulate the action of growth factors.

Cell Survival↗
PubMed2001

Apnoea of prematurity and arousal from sleep.

The incidence of sudden infant death syndrome (SIDS) has been found to be consistently higher in preterm and low birth weight infants than in infants born at term and this increase is inversely related to gestational age. The incidence and severity of apnoea of prematurity, are also inversely related to gestational age. The aim of this study was to investigate whether a neonatal history of apnoea/bradycardia affected the maturation of arousal responses. Twenty-five premature infants were studied. A perinatal risk score was determined for each infant and infants were divided into those with a neonatal history of apnoea/bradycardia (n=16) and those without (n=9). All infants were studied using daytime polysomnography on three occasions: (a) a preterm study around 36 weeks gestation, (b) within 3 weeks of term, and (c) 2-3 months post-term. Multiple measurements of arousal threshold (cm H2O) in response to air-jet stimulation applied alternately to the nares were made in both active sleep (AS) and quiet sleep (QS). Arousal thresholds were elevated in apnoeic infants compared to control infants in both AS (P<0.05) and QS (P<0.001) at the term study and in QS at 2-3 months post-term (P<0.01). In addition, arousal thresholds were positively correlated with perinatal risk score in both sleep states, in all studies, with the exception of AS at 2-3 months when all infants were readily arouseable. We conclude that a history of prematurity with neonatal apnoea has a persisting effect on decreasing arousabilty from sleep and these infants may be at increased risk for SIDS.

Apnea↗
PubMed2001

trans-3,4-dihydroxy-anti-1,2-epoxy-1,2,3,4-tetrahydrodi- benz[a,j]acridine involvement in dibenz[a,j]acridine DNA adduct formation in mouse skin consistent with Ha-ras mutation patterns in tumors.

Dibenz[a,j]acridine (DBA), is a N-heteropolycyclic aromatic environmental carcinogen found in complex combustion mixtures. The major route of DBA metabolic activation is reportedly through the trans-3,4-dihydroxy-3,4-dihydroDBA (DBA-3,4-DHD). The present studies were undertaken to determine the role of trans-3,4-dihydroxy-anti-1,2-epoxy-1,2,3,4-tetrahydroDBA (DBADE) in DBA activation pathway(s), the DNA bases involved in the binding of DBA to DNA, and whether the adducts produced are consistent with the mutation pattern in the Ha-ras gene. DBA (300 microg) or 50 microg synthesized (+/-)-DBADE was applied to the back of female Hsd:ICR(Br) mice. The mice were sacrificed 48 h later, and skin DNA was isolated, hydrolyzed, and analyzed with (32)P-postlabeling. Of the four adducts produced in vivo, adduct 1 was the major adduct for DBA (>50%) and adduct 2 was the major adduct for DBADE (89%). After the reaction of (+/-)-DBADE with purine nucleotides or calf thymus (CT) DNA in vitro, 100% of the DBADE-2'-dAMP adducts and 94% of DBADE-CT DNA adducts were chromatographically identical on TLC with adduct 2 and 86% of the DBADE-2'-dGMP adducts were chromatographically consistent with adduct 1 by (32)P-postlabeling. Papillomas were induced on the backs of mice by a single application of 0.2 micromol of DBA followed by twice-weekly application of 12-o-tetra-decanoylphorbol-13-acetate (TPA, 2 microg) for 24-26 weeks. Skin carcinomas were induced by twice weekly applications of DBA (0.1 micromol) on the backs of mice. A to T and G to T transversions were found in codons 12, 13, and 61 of the Ha-ras gene in the treated mouse skin carcinoma and papilloma DNA. The mutational spectra in the Ha-ras gene are consistent with the DNA binding of DBA to dG or dA in vivo. Thus, this research has indicated that DBADE plays an important role in DBA metabolic activation and DNA binding in mouse skin, and an alternative pathway through a bis-dihydrodiol-epoxide of DBA may also be involved.

Acridines↗