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Biomedical subjects

M Harrison

Publications and source records attributed to M Harrison.

At least 19 recordsLinked to original sources
PubMed2005

Can pathological complete response in the primary tumour following pre-operative pelvic chemoradiotherapy for T3-T4 rectal cancer predict for sterilisation of pelvic lymph nodes, a low risk of local recurrence and the appropriateness of local excision?

INTRODUCTION: Local excision is considered inappropriate treatment for T3-T4 rectal adenocarcinomas, as it cannot provide prognostic information regarding lymph node involvement and has a high risk of pelvic recurrence. Preoperative chemoradiation (CRT) studies in rectal cancer suggest that a pathological complete response (pCR) in the primary tumour provides an excellent long-term outcome. If downstaging to stage pT0 predicts a tumour response within the perirectal and pelvic lymph nodes, this may allow local excision to be performed without increased risk of pelvic recurrence. This retrospective study aimed to determine the incidence of involved lymph nodes following pCR (ypT0) after preoperative CRT and total mesorectal excision. METHOD: The outcome and treatment details of 211 patients undergoing preoperative CRT for clinically staged T3-T4 unresectable rectal adenocarcinomas between 1993 and 2003 at Mount Vernon Hospital were reviewed. RESULTS: Data were recorded from the 143 patients who completed treatment with a median follow-up of 25 months. Twenty-three patients (18%) were found to have had a pCR. Four out of 23 patients (17%) had involved lymph nodes. No pelvic recurrences developed after a ypCR. Overall survival was similar for patients with ypT0 or residual tumour. CONCLUSION: Pathological complete response in the primary tumour failed to predict a response in the perirectal lymph nodes (p=0.08). The degree of response predicted a lymph node response (p=0.02). The detection of ypCR identified patients with a low rate of pelvic recurrence. This may in the future allow selection of patients for whom local excision can be performed without a higher risk of local relapse.

Adenocarcinoma↗
PubMed2005

Automated neuropsychological assessment metrics (ANAM) measures of cognitive effects of Alzheimer's disease.

Eight individuals with Alzheimer's disease, and eight age-matched controls, were administered the MMSE, the Yesavage GDS, and a customized subset of the Automated Neuropsychological Assessment Metrics (ANAM) Battery. Accuracy (percent correct) and efficiency (number of correct responses per minute) of performance on six ANAM tasks were assessed. The patients' GDS scores indicated no depression. Although their MMSE scores (mean approximately 25) were significantly lower than those of the controls, they nonetheless indicated that the patients were still functioning at a fairly high level. Analysis of ANAM accuracy scores indicated that the patients were significantly impaired on three tasks measuring working memory. A discriminant function analysis revealed 93.8% correct classification. Analysis of ANAM efficiency scores revealed that except for simple reaction time, the patients were significantly impaired on all tasks. A discriminant function analysis correctly classified 100% of the participants. Given the small size of the groups in the present study, this finding especially underscores the sensitivity of ANAM to the cognitive effects of Alzheimer's disease, as indicated by the large effect sizes. The findings further indicate that ANAM might be capable of detecting more subtle effects of the disease at an earlier stage in its progress.

Aged↗
PubMed2005

Simple nomograms to calculate sample size in diagnostic studies.

OBJECTIVES: To produce an easily understood and accessible tool for use by researchers in diagnostic studies. Diagnostic studies should have sample size calculations performed, but in practice, they are performed infrequently. This may be due to a reluctance on the part of researchers to use mathematical formulae. METHODS: Using a spreadsheet, we derived nomograms for calculating the number of patients required to determine the precision of a test's sensitivity or specificity. RESULTS: The nomograms could be easily used to determine the sensitivity and specificity of a test. CONCLUSIONS: In addition to being easy to use, the nomogram allows deduction of a missing parameter (number of patients, confidence intervals, prevalence, or sensitivity/specificity) if the other three are known. The nomogram can also be used retrospectively by the reader of published research as a rough estimating tool for sample size calculations.

Diagnostic Techniques and Procedures↗
PubMed2004

Multiple transcripts of a gene for a leucine-rich repeat receptor kinase from morning glory (Ipomoea nil) originate from different TATA boxes in a tissue-specific manner.

TATA boxes are the most common regulatory elements found in the promoters of eukaryotic genes because they are associated with basal transcription initiation by RNA polymerase II. Often only a single TATA element is found in a given promoter, and tissue-, stage- and/or stimulus-specific expression occurs because the TATA box is associated with other cis -acting elements that enhance or repress transcription. We used software tools for gene analysis to assist in locating potential TATA box(es) in an AT-rich region of the promoter of a gene, inrpk1, which codes for a leucine-rich receptor protein kinase in morning glory (Ipomoea nil). Through the use of RT-PCR and various combinations of forward primers bracketing most of the promoter region we were able to define the 5'-ends of transcripts in this region. The region was then targeted for analysis by RNA Ligase-Mediated-5' Rapid Amplification of cDNA Ends (RLM-5' RACE) to identify the transcript initiation site(s). Positioning of initiation sites with respect to TATA boxes identified by gene analysis tools allowed us to identify three operational TATA elements which regulate basal transcription from this gene. Two TATA boxes were responsible for all of the inrpk1 transcripts found in leaves and cotyledons, and about 25-30% of the transcripts in roots. A third TATA box was involved only in expression in roots and accounted for the remaining 50-70% of root transcripts. RNAs expressed from this element lack two potentially functional upstream AUG codons, and may be translated more efficiently than transcripts originating from the other TATA boxes.

Alternative Splicing↗
PubMed2004

Social exclusion in clients with comorbid mental health and substance misuse problems.

BACKGROUND: The concept of comorbid mental health problems and substance misuse has gained prominence in the last two decades, due in part to the closure of large psychiatric hospitals and to the increasing prevalence of drug use in the community. This client group has a dual requirement for both medical and social care needs and is at risk for social exclusion. METHODS: A retrospective matched case-control study to examine aspects of social exclusion between service users who have comorbid diagnoses and those with a single diagnosis. Samples were drawn from the service users of a mental health Trust in the South-East of England, from both Adult Mental Health (n = 400) and Drug and Alcohol services (n = 190). Data were collected from Care Programme Approach assessment forms and medical records. McNemar's chi(2) and odds ratios via a conditional logit regression model are used to test for differences in the social exclusion indicators. RESULTS: There were significant differences in social exclusion between the comorbid and singly diagnosed clients of the Adult Mental Health service, but differences were less pronounced between the comorbid and singly diagnosed clients of the specialist Drug and Alcohol service. CONCLUSIONS: Recent Government policy advocates treating comorbid clients within mainstream mental health services. Health care workers need to recognise the likelihood of high levels of social exclusion among clients with comorbid problems.

Adolescent↗
PubMed2004

Fulvestrant: pharmacokinetics and pharmacology.

Fulvestrant is a new type of oestrogen receptor (ER) antagonist with no agonist activity and a novel pharmacological profile. Fulvestrant has been shown to significantly reduce cellular levels of the ER and progesterone receptor in both preclinical studies and in clinical trials of postmenopausal women with primary breast cancer. This paper reviews the pharmacokinetics and metabolism of fulvestrant, which support the rationale for drug delivery as a single, once-monthly intramuscular injection, and show that this agent has minimal potential to be the subject, or cause, of significant cytochrome p450-mediated drug interactions.

Animals↗
PubMed2004

Defining dual diagnosis of mental illness and substance misuse: some methodological issues.

This paper discusses methodological issues arising in the initial stages of a larger epidemiological case-control study. Practitioners from both Generic Mental Health and Substance Misuse Services (n = 170) were asked to identify which of their clients, from a time-limited caseload (n = 2341), had comorbid mental health and substance misuse problems. Although practitioners were provided with a definition of 'singly diagnosed' and 'dually diagnosed', it became apparent that these definitions were applied pragmatically, depending on the nature of the client's primary problem and the agency they were presenting to. Issues raised include the time period in which a client was considered to have a concurrent mental health problem and substance misuse, how a 'mental health problem' was defined and whether a personality disorder should be categorized as a 'mental health problem'. There was also some disagreement about whether clients who were being treated primarily by Substance Misuse Services, but were also taking prescribed antidepressants, implicitly had a 'mental health problem'. We raise these methodological issues, as they have implications for determining the prevalence of 'dual diagnosis' and the subsequent provision of services.

Adult↗
PubMed2004

Continuing education and New Zealand anaesthetists: an analysis of current practice and future needs.

A survey of Continuing Medical Education (CME) of New Zealand anaesthetists was undertaken to identify current patterns of participation, usefulness of different activities, evidence of effectiveness, motivators and barriers to participation and to define future CME needs. The response rate was 74% and showed high levels of participation in a range of CME activities. Ratings for usefulness differed significantly between these activities. Respondents identified specific changes they had made to their practice as a result of CME, providing strong evidence for its effectiveness. Anaesthetists valued interactive methods of learning that were relevant to clinical practice. The most commonly reported motivators for participation were accreditation requirements and keeping up to date, while other work commitments were the commonest impediment. In this survey, interactive educational interventions were seen as useful, a finding consistent with systematic reviews of the effectiveness of CME in changing physician behaviour. Such reviews conclude that there is no evidence that conferences are effective in changing physician behaviour, yet respondents to this survey attributed many changes in practice to their attendance at a conference. Analysis of the needs of NZ anaesthetists supports increasing the number of workshops and interactive sessions and promoting smaller meetings and practice-based activities. The survey provides a basis for designing a future program of CME for New Zealand.

Anesthesiology↗
PubMed2004

Factors inducing in-stent restenosis: an in-vitro model.

In-stent restenosis is caused by the proliferation of the smooth muscle cells (SMCs) following a host response towards the implanted device. However, the precise biochemical and cellular mechanisms are still not completely understood. In this paper, the behaviour of SMCs has been investigated by an in vitro model where the cells were stimulated by platelet derived growth factor (PDGF) on tissue-like substrates as well as on biomaterials such as stainless steel (St) and diamond-like carbon (DLC)-coated St. The results demonstrated that SMCs have a completely different adhesion mode on St and become particularly prone to proliferation and pro-inflammatory cytokine secretion under PDGF stimulus. This would suggest that restenosis may caused by the accidental contact of the SMC with the St substrate under an inflammatory insult.

Carbon↗
PubMed2003

Interaction of normal and expanded CAG repeat sizes influences age at onset of Huntington disease.

Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. Past studies have shown that the size of expanded CAG repeat is inversely associated with age at onset (AO) of HD. It is not known whether the normal Huntington allele size influences the relation between the expanded repeat and AO of HD. Data collected from two independent cohorts were used to test the hypothesis that the unexpanded CAG repeat interacts with the expanded CAG repeat to influence AO of HD. In the New England Huntington Disease Center Without Walls (NEHD) cohort of 221 HD affected persons and in the HD-MAPS cohort of 533 HD affected persons, we found evidence supporting an interaction between the expanded and unexpanded CAG repeat sizes which influences AO of HD (P = 0.08 and 0.07, respectively). The association was statistically significant when both cohorts were combined (P = 0.012). The estimated heritability of the AO residual was 0.56 after adjustment for normal and expanded repeats and their interaction. An analysis of tertiles of repeats sizes revealed that the effect of the normal allele is seen among persons with large HD repeat sizes (47-83). These findings suggest that an increase in the size of the normal repeat may mitigate the expression of the disease among HD affected persons with large expanded CAG repeats.

Adolescent↗
PubMed2003

Contribution of clinical breast examination to mammography screening in the early detection of breast cancer.

OBJECTIVES: As the benefit of clinical breast examination (CBE) over that of screening mammography alone in reducing breast cancer mortality is uncertain, it is informative to monitor its contribution to interim measures of effectiveness of a screening programme. Here, the contribution of CBE to screening mammography in the early detection of breast cancer was evaluated. SETTING: Four Canadian organised breast cancer screening programmes. METHODS: Women aged 50-69 receiving dual screening (CBE and mammography) (n = 300,303) between 1996 and 1998 were followed up between screen and diagnosis. Outcomes assessed by mode of detection (CBE alone, mammography alone, or both CBE and mammography) included referral rate, positive predictive value, pathological features of tumours (size, nodal status, morphology), and cancer detection rates overall and for small cancers (< or = 10 mm or node-negative). Heterogeneity in findings across programmes was also assessed. RESULTS: On first versus subsequent screen, CBE alone resulted in 28.5-36.7% of referrals, and 4.6-5.9% of cancers compared with 52.6-60.1% of referrals and 60.0-64.3% of cancers for mammography alone. Among cancers detected by CBE, 83.6-88.6% were also detected by mammography, whereas for mammographically detected cancers only 31.7-37.2% were also detected by CBE. On average, CBE increased the rate of detection of small invasive cancers by 2-6% over rates if mammography was the sole detection method. Without CBE, programmes would be missing three cancers for every 10,000 screens and 3-10 small invasive cancers in every 100,000 screens. CONCLUSIONS: Inclusion of CBE in an organised programme contributes minimally to early detection.

Breast Neoplasms↗
PubMed2002

Evaluation of a selective medium for Brucella isolation using natamycin.

AIMS: To select an anti-fungal agent to replace cycloheximide in the media used for isolation of Brucella. METHODS AND RESULTS: One potential agent, natamycin, was evaluated using 28 Brucella isolates, 18 yeasts and 14 fungi. The material for the evaluation included 37 bovine milk samples, six bovine vaginal swabs and 45 milk samples artificially infected with Brucella. The recovery of Brucella only from the artificially-inoculated milk samples increased with the use of the medium containing natamycin instead of cycloheximide, at the same time significantly inhibiting the growth of yeasts, fungi and other bacteria. The inclusion of either anti-fungal agent allowed growth of the 28 Brucella isolates and totally prevented the growth of all 18 yeasts and 13 of the 14 fungi. CONCLUSIONS: Based on the results it was concluded that natamycin would be a suitable alternative to cycloheximide. SIGNIFICANCE AND IMPACT OF THE STUDY: Cycloheximide has become unavailable worldwide and is currently an anti-fungal constituent of the medium often used for isolation of Brucella organisms. The use of natamycin as a replacement in the formulation did not inhibit growth of Brucella and was effective at eliminating most contaminants.

Animals↗
PubMed2002

Evaluation of selective media for Campylobacter isolation when cycloheximide is replaced with amphotericin B.

AIMS: Laboratory media for the isolation of Campylobacter usually contain various selective agents, designed to allow these bacteria to grow whilst suppressing that of other organisms. For example, cycloheximide has often been incorporated into Campylobacter media to inhibit the growth of fungi. The production and availability of cycloheximide, however, has recently decreased due to concerns relating to its potential toxicity for mammalian cells and the compound has also become more expensive as a result. An alternative antifungal agent is necessary, and to address this, the effect of using amphotericin B in place of cycloheximide in Campylobacter selective broths and agars was examined. METHODS AND RESULTS: The growth of Campylobacter strains and the suppression of potential competitor organisms in selective broths or on selective agars containing either amphotericin B or cycloheximide was quantified, using pure microbial cultures. The results were then confirmed by testing food and water samples that contained high levels of micro-organisms, including Campylobacter. CONCLUSIONS: The results of this study indicate that amphotericin B is a suitable replacement for cycloheximide in Campylobacter selective media.

Amphotericin B↗
PubMed2002

Experience with laparoscopic adrenalectomy in pediatric patients.

BACKGROUND: Laparoscopic adrenalectomy (LA) is now being recognized as the standard in the management of benign adrenal pathology in adult patients. Few reports have described the use of this technique in pediatric patients. This study combines experience from 2 institutions with lateral transperitoneal LA in children to analyze our results and the clinical and biochemical response to laparoscopic adrenalectomy in patients with hormonally active adrenal tumors. METHODS: A bi-institutional retrospective review of all patients undergoing LA between January 1997 and January 2001 was performed. Clinical and biochemical data were obtained during routine follow-up. RESULTS: Seventeen laparoscopic adrenalectomies were performed during this period. The average operating time was 120 minutes, mean estimated blood loss was 25 mL, the mean size of the adrenal lesion was 4.8 cm, and the mean length of hospitalization was 35 hours. Resolution of clinical and biochemical parameters of adrenal hyperfunction was accomplished in all patients with adrenocortical hyperplasia and pheochromocytoma in postoperative follow-up. CONCLUSIONS: Laparoscopic adrenalectomy can be performed safely and effectively with a short hospital stay, minimal blood loss, and excellent functional outcome in this age group. The authors believe laparoscopic adrenalectomy is an excellent approach for the management of benign pediatric adrenal pathology.

Adenoma↗