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Biomedical subjects

Jennifer Harris

Publications and source records attributed to Jennifer Harris.

16 recordsLinked to original sources
PubMed2006

Effect of bupropion on physiological measures of stress in smokers during nicotine withdrawal.

Studies suggest that among cigarette smokers trying to quit, stress undermines abstinence. Little research has assessed if therapies that increase smoking cessation rates impact physiological measures of stress response. Forty-three subjects completed this repeated-measures study in which a laboratory assessment was completed at baseline and after 17 days of treatment with either placebo (n=15), bupropion sustained release (150 mg twice daily) (n=14) or bupropion with stress reduction counseling (n=14). All subjects quit smoking 3 days prior to the second laboratory assessment. At each laboratory assessment physiological measures of stress (i.e. blood pressure, heart rate, plasma epinephrine, norepinephrine and cortisol concentrations) were measured during rest periods and in response to a speech, a math and a cold pressor task. Among subjects taking placebo, physiological measures of stress were generally lower at rest and during the stressors after smoking cessation. In those taking bupropion these measures were equivalent at the two assessments. Additionally, compared to placebo, those on bupropion had a greater diastolic blood pressure response to the speech stressor and greater systolic blood pressure response to the math stressor during the second laboratory session. This study suggests that bupropion may be maintaining physiological measures of stress during the nicotine withdrawal period.

Adult↗
PubMed2006

Personalised social care for adults with disabilities: a problematic concept for frontline practice.

This paper explores the complexities and contradictions of frontline practice that pose problems for personalised social care through enhanced choice. It draws on semi-structured interviews with community care workers, social workers, occupational therapists and care managers in a social service department. Practitioners interviewed were asked about their current assessment and documentation system, including the assessment documents currently used; how they approached information gathering and the topics they explored with service users; and their experience of documenting assessment and care management. The paper argues that the validity and sustainability of personalised social care in frontline practice relies on developing a thorough understanding of the complex and implicit assessment processes operating at the service user/practitioner interface and the inevitable tensions that arise for practitioners associated with the organisational context and broader service environment. The findings demonstrate the variability among practitioners in how they collect information and more importantly, the critical role practitioners occupy in determining the kinds of topics to be explored during the assessment process. In so doing, it shows how practitioners can exert control over the decision-making process. More importantly, it provides some insight into how such processes are shaped by the constraints of the organisational context and broader service environment. Complexities and contradictions may be an inherent part of frontline practice. The issues discussed in this paper, however, highlight potential areas that might be targeted in conjunction with implementing personalised social care through enhanced choice for people with disabilities.

Adult↗
PubMed2005

Study of the biologic effects of lapatinib, a reversible inhibitor of ErbB1 and ErbB2 tyrosine kinases, on tumor growth and survival pathways in patients with advanced malignancies.

PURPOSE: This was a pilot study to assess the biologic effects of lapatinib on various tumor growth/survival pathways in patients with advanced ErbB1 and/or ErbB2-overexpressing solid malignancies. PATIENTS AND METHODS: Heavily pretreated patients with metastatic cancers overexpressing ErbB2 and/or expressing ErbB1 were randomly assigned to one of five dose cohorts of lapatinib (GW572016) administered orally once daily continuously. The biologic effects of lapatinib on tumor growth and survival pathways were assessed in tumor biopsies obtained before and after 21 days of therapy. Clinical response was determined at 8 weeks. RESULTS: Sequential tumor biopsies from 33 patients were examined. Partial responses occurred in four patients with breast cancer, and disease stabilization occurred in 11 others with various malignancies. Responders exhibited variable levels of inhibition of p-ErbB1, p-ErbB2, p-Erk1/2, p-Akt, cyclin D1, and transforming growth factor alpha. Even some nonresponders demonstrated varying degrees of biomarker inhibition. Increased tumor cell apoptosis (TUNEL) occurred in patients with evidence of tumor regression but not in nonresponders (progressive disease). Clinical response was associated with a pretreatment TUNEL score > 0 and increased pretreatment expression of ErbB2, p-ErbB2, Erk1/2, p-Erk1/2, insulin-like growth factor receptor-1, p70 S6 kinase, and transforming growth factor alpha compared with nonresponders. CONCLUSION: Lapatinib exhibited preliminary evidence of biologic and clinical activity in ErbB1 and/or ErbB2-overexpressing tumors. However, the limited sample size of this study and the variability of the biologic endpoints suggest that further work is needed to prioritize biomarkers for disease-directed studies, and underscores the need for improved trial design strategies in early clinical studies of targeted agents.

Adult↗
PubMed2005

'Think before you buy under-18s drink': evaluation of a community alcohol intervention.

Hazardous consumption of alcohol by teenagers is a significant public health problem in New Zealand. Concern about supply of alcohol to minors motivated 'Think before you buy under-18s drink', a campaign to reduce alcohol-related harm by discouraging inappropriate supply of alcohol by adults. Two intervention districts and a comparison district, in the South Island of New Zealand, were selected for the purpose of evaluating the campaign. Primary outcome measures were changes in the prevalence of parent supply to their teenager (13-17 years) for unsupervised drinking (SUD), and changes in the prevalence of binge drinking among teenagers. At baseline, 49% of teenagers reported a recent episode of binge drinking. SUD in the past month was reported by 36% of teenagers. Recent purchases of alcohol by under-18s were common (bottle shops: 16%; pubs/bars: 11%). In contrast to teenagers, only 2% of parents reported SUD in the past month. Levels of binge drinking decreased in all three districts. Analysis of data from 474 teenagers who completed questionnaires, at baseline and follow-up, showed decreased SUD in Ashburton and Waitaki relative to Clutha, although this was not significant (OR=0.73; 95% CI: 0.43, 1.25). Discrepancies between teenager and parent reports of SUD may be due to the latter providing a socially desirable survey response and to differences in the interpretation of what constitutes adult supervision. The lack of a significant association between changes in SUD and binge drinking may be a consequence of teenagers obtaining relatively small amounts of alcohol from their parents and larger quantities from other sources, e.g. peers (some of whom may be able to purchase alcohol legally) and from licensed premises.

Adolescent↗
PubMed2005

Inhibition of CYP2D6 activity by bupropion.

The purpose of this study was to assess the effect of bupropion on cytochrome P450 2D6 (CYP2D6) activity. Twenty-one subjects completed this repeated-measures study in which dextromethorphan (30-mg oral dose) was administered to smokers at baseline and after 17 days of treatment with either bupropion sustained-release (150 mg twice daily) or matching placebo. Subjects quit smoking 3 days before the second dextromethorphan administration. To assess CYP2D6 activity, urinary dextromethorphan/dextrorphan metabolic ratios were calculated after an 8-hour urine collection. Thirteen subjects received bupropion, and 8 received placebo. In those receiving active medication, the dextromethorphan/dextrorphan ratio increased significantly at the second assessment relative to the first (0.012 +/- 0.012 vs. 0.418 +/- 0.302; P < 0.0004). No such change was observed in those randomized to placebo (0.009 +/- 0.010 vs. 0.017 +/- 0.015; P = NS). At baseline, all subjects were phenotypically extensive CYP2D6 metabolizers (metabolic ratio <0.3); after treatment, 6 of 13 subjects receiving bupropion, but none of those receiving placebo, had metabolic ratios consistent with poor CYP2D6 metabolizers. Bupropion is therefore a potent inhibitor of CYP2D6 activity, and care should be exercised when initiating or discontinuing bupropion use in patients taking drugs metabolized by CYP2D6.

Adult↗
PubMed2005

Regulation of arginase II by interferon regulatory factor 3 and the involvement of polyamines in the antiviral response.

The innate antiviral response requires the induction of genes and proteins with activities that limit virus replication. Among these, the well-characterized interferon beta (IFNB) gene is regulated through the cooperation of AP-1, NF-kappaB and interferon regulatory factor 3 (IRF-3) transcription factors. Using a constitutively active form of IRF-3, IRF-3 5D, we showed previously that IRF-3 also regulates an IFN-independent antiviral response through the direct induction of IFN-stimulated genes. In this study, we report that the arginase II gene (ArgII) as well as ArgII protein concentrations and enzymatic activity are induced in IRF-3 5D-expressing and Sendai virus-infected Jurkat cells in an IFN-independent manner. ArgII is a critical enzyme in the polyamine-biosynthetic pathway. Of the natural polyamines, spermine possesses antiviral activity and mediates apoptosis at physiological concentrations. Measurement of intracellular polyamine content revealed that expression of IRF-3 5D induces polyamine production, but that Sendai virus and vesicular stomatitis virus infections do not. These results show for the first time that the ArgII gene is an early IRF-3-regulated gene, which participates in the IFN-independent antiviral response through polyamine production and induction of apoptosis.

Apoptosis↗
PubMed2004

Activity profile of dust mite allergen extract using substrate libraries and functional proteomic microarrays.

Enzymatic activity in the fecal droppings from the house dust mite has been postulated to contribute to the elicited allergic response. Screening dust mite extracts through 137,180 tetrapeptide fluorogenic substrates allowed for the characterization of proteolytic substrate specificity from the potential cysteine and serine proteases in the extract. The extract was further screened against a 4000 member peptide nucleic acid (PNA) encoded inhibitor library designed to target cysteine proteases using microarray detection. Affinity chromatography coupled with mass spectrometry identified Der p 1 as one of the proteases targeted by the PNA inhibitors in the dust mite lysate. A phenotypic readout of Der p 1 function in allergy progression was demonstrated by the inhibition of CD25 cleavage from T cells by dust mite extract that had been treated with the Der p 1 inhibitor identified from the PNA-encoded inhibitor library.

Amino Acid Sequence↗
PubMed2003

Synthesis of crystalline skutterudite superlattices using the modulated elemental reactant method.

A series of samples ((AB)(x)(CD)(y))(z) were prepared containing both short repeat units (AB and CD) and long repeat units ((AB)(x)(CD)(y)), where the short repeat units were designed to have the composition appropriate to form square M(4)Sb(12) skutterudites (M = Fe, Co, or Ir; square = vacancy, La, or Y). X-ray diffraction and reflectivity were used to follow the evolution of the films from amorphous, layered materials to crystalline skutterudite superlattices as a function of annealing temperature and time. In all cases, the short repeat units interdiffused and crystallized the expected skutterudite, while the long repeat period persisted after annealing. The skutterudites crystallize with random crystallographic orientation with respect to the substrate. The observed splitting of the peaks in the high-angle diffraction data from the IrSb(3)/CoSb(3) sample indicates the formation of a novel superlattice structure with each grain having a random crystallographic orientation of the skutterudite lattice with respect to the superlattice direction.

Journal Article↗
PubMed2003

Group problems in problem-based learning.

Successful small-group learning in problem-based learning (PBL) educational programmes relies on functional group processes. However, there has been limited research on PBL group problems, and no studies have been conducted on problems as perceived by both students and tutors in the same educational context. The authors investigated PBL group problems in a graduate-entry medical programme, and report the most common group problems, and those that hinder students' learning the most. The possible causes of individual quietness and dominant behaviour, and potential influences that group problems may have on the tutorial process are summarized in an exploratory model of PBL group dysfunction that could be used to guide further research. Specifically, there is a need for further evidence on which to base guidelines for tutors and students to effectively manage group problems.

Adaptation, Psychological↗
PubMed2003

Abdominal aortic aneurysm demonstrated on renal scintigraphy.

A 74-year-old hypertensive woman presented with abdominal discomfort and a pulsatile abdominal mass. Anterior abdominal angiography during cardiac blood pool, and renal scintigraphic imaging demonstrated a large abdominal aortic aneurysm. 1, 2 Before endovascular repair with an aortoiliac endograft, the abdominal aneurysm measured 7.5 x 7.0 cm on abdominal computed tomography. This study demonstrates that a suspected abdominal aortic aneurysm can be confirmed using the addition of anterior abdominal imaging with normal posterior imaging at the time of renal scintigraphy.

Aged↗
PubMed2003

Prior Alcoholics Anonymous (AA) affiliation and the acceptability of the Twelve Steps to patients entering UK statutory addiction treatment.

OBJECTIVE: The study investigates levels of affiliation with AA and beliefs about the organization and its philosophy among a cohort of alcoholics entering a UK (non-AA) alcohol treatment service. METHOD: A total of 150 consecutive admissions (75% men) were interviewed by an independent researcher within 5 days of their entry into a residential alcohol treatment unit. RESULTS: Although about three quarters of these patients had previously attended AA meetings, levels of affiliation were low, with only 16% having worked any of the Twelve Steps. Previous AA attenders were more likely to be older, drinking greater daily quantities prior to treatment and to have first sought alcohol treatment at a younger age. Roughly equal groups expressed "positive," "neutral" and "negative" current attitudes towards AA (38%, 36% and 26%, respectively). Each of these three AA-attitude groups expressed greater endorsement of "Personal Responsibility" steps than of "Higher Power mediated" steps. CONCLUSIONS: Few participants were universally negative to AA or the Twelve Steps--most regarded some of the steps as positive, but many rejected those referring to a Higher Power. Most also regarded some aspects of the organization and its philosophy worthwhile, with attitudes spread across the continuum of opinion. As AA remains one of the most widely sought forms of help for alcohol problems, a clearer understanding is needed of its impact on patients and the appropriateness of its integration within substance misuse programs which are not explicitly Twelve Step in orientation.

Adult↗
PubMed2002

Modulation of leukotriene B4 receptor-1 expression by dexamethasone: potential mechanism for enhanced neutrophil survival.

Glucocorticoids can down-regulate many inflammatory and immune responses and constitute a powerful therapeutic tool in a number of diseases. However, they have a somewhat paradoxical effect on neutrophils, in that they prolong their survival. Because leukotriene B(4) (LTB(4)) can also extend neutrophil survival, we proposed that glucocorticoids could prevent neutrophil apoptosis by up-regulating their expression of the high-affinity LTB(4) receptor (BLT1). Here we show that, indeed, dexamethasone (DEX) up-regulates the steady-state levels of BLT1 mRNA in human neutrophils. The effect was time and concentration dependent, being maximal at 4 h and at 10-100 nM DEX. The effect was also dependent on transcriptional activity, whereas BLT1 mRNA stability was not affected. DEX-induced up-regulation of BLT1 expression was prevented by pretreatment with the LTB(4) antagonist LY255283. Moreover, LTB(4) itself up-regulated the expression of BLT1 mRNA. BLT1 protein expression on neutrophils exposed to DEX for 24 h was also up-regulated 2- to 3-fold, and DEX-treated as well as LTB(4)-treated cells showed enhanced responsiveness to LTB(4) in terms of intracellular Ca(2+) mobilization and chemotaxis. Whereas DEX and LTB(4) alone decreased neutrophil apoptosis by approximately 50%, neutrophils treated with both LTB(4) and DEX showed >90% survival at 24 h. Moreover, BLT1 antagonists prevented the increased neutrophil survival induced by DEX as well as by LTB(4). Taken together, our results suggest that DEX-induced up-regulation of BLT1 expression in neutrophils may be one mechanism through which glucocorticoids can prolong neutrophil survival, namely by enhancing cell responses to the antiapoptotic effect of LTB(4).

Adjuvants, Immunologic↗
PubMedDate not supplied

Is attendance at Alcoholics Anonymous meetings after inpatient treatment related to improved outcomes? A 6-month follow-up study.

AIMS: This study investigates the relationship between attendance at Alcoholics Anonymous (AA) meetings prior to, during, and after leaving treatment, and changes in clinical outcome following inpatient alcohol treatment. METHODS: A longitudinal design was used in which participants were interviewed at admission (within 5 days of entry), and 6 months following departure. The sample comprised 150 patients in an inpatient alcohol treatment programme who met ICD-10 criteria for alcohol dependence. The full sample was interviewed at admission to treatment. Six months after departure from treatment, 120 (80%) were re-interviewed. RESULTS: Significant improvements in drinking behaviours (frequency, quantity and reported problems), psychological problems and quality of life were reported. Frequent AA attenders had superior drinking outcomes to non-AA attenders and infrequent attenders. Those who attended AA on a weekly or more frequent basis after treatment reported greater reductions in alcohol consumption and more abstinent days. This relationship was sustained after controlling for potential confounding variables. Frequent AA attendance related only to improved drinking outcomes. Despite the improved outcomes, many of the sample had alcohol and psychiatric problems at follow-up. CONCLUSIONS: The importance of aftercare has long been acknowledged. Despite this, adequate aftercare services are often lacking. The findings support the role of Alcoholics Anonymous as a useful aftercare resource.

Adult↗