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Biomedical subjects

J Young

Publications and source records attributed to J Young.

At least 19 recordsLinked to original sources
PubMed2007

Calorie restriction in nonhuman primates: assessing effects on brain and behavioral aging.

Dietary caloric restriction (CR) is the only intervention repeatedly demonstrated to retard the onset and incidence of age-related diseases, maintain function, and extend both lifespan and health span in mammals, including brain and behavioral function. In 70 years of study, such beneficial effects have been demonstrated in rodents and lower animals. Recent results emerging from ongoing studies of CR in humans and nonhuman primates suggest that many of the same anti-disease and anti-aging benefits observed in rodent studies may be applicable to long-lived species. Results of studies in rhesus monkeys indicate that CR animals (30% less than controls) are healthier than fully-fed counterparts based on reduced incidence of various diseases, exhibit significantly better indices of predisposition to disease and may be aging at a slower rate based on analysis of selected indices of aging. The current review discusses approaches taken in studies of rhesus monkeys to analyze age-related changes in brain and behavioral function and the impact of CR on these changes. Approaches include analyses of gross and fine locomotor performance as well as brain imaging. In a related study it was observed that short-term CR (6 months) in adult rhesus monkeys can provide protection against a neurotoxic insult. Increasing interest in the CR paradigm will expand its role in demonstrating how nutrition can modulate the rate of aging and the mechanisms responsible for this modulation.

Aging↗
PubMed2007

Biomarkers of oxidative stress in schizophrenic and control subjects.

Increasing evidence indicates that oxidative injury exists in schizophrenia. Although it may not be the main cause, oxidative damage has been suggested to contribute to the pathophysiology and may account for deteriorating course and poor outcome in schizophrenia. A human study was undertaken, therefore, to investigate possible differences in biomarkers of DNA, lipid and protein oxidation in schizophrenic (n=16) and control subjects (n=17). Plasma vitamin C levels were also compared in both groups. Cellular DNA damage and plasma protein carbonyl levels were increased in the schizophrenic group compared to control subjects but not significantly. However, DNA damage in lymphocytes from the male schizophrenic group was significantly higher than the female group. Biomarkers of lipid peroxidation and plasma vitamin C levels also revealed no significant difference between the two groups under investigation, although a significant elevation in plasma vitamin C was observed in the female control group when compared to the male groups.

Adult↗
PubMed2006

A pilot study to evaluate the impact of involving breast cancer patients in the multidisciplinary discussion of their disease and treatment plan.

Multidisciplinary care is the accepted best model of management of breast cancer patients. Current evidence suggests that multidisciplinary care has the potential to reduce mortality, improve quality of life, and reduce health care costs. We investigated the impact of patient involvement in the multidisciplinary meeting. A pilot study was conducted to assess the feasibility and acceptability of directly involving patients diagnosed with breast cancer in multidisciplinary clinic discussions and treatment planning. 30 consecutive breast cancer patients presenting for surgery were invited to attend our weekly multidisciplinary breast meeting at the time of receiving their results of surgery. Patients completed questionnaires before and after the meeting, and participated in a tape-recorded interview with the breast care nurse after the meeting. Members of the multi-disciplinary team also completed a short survey at the end of the study. The intervention was highly valued by most of the participating patients; and acceptable to and welcomed by most health professionals in the multidisciplinary team. Change in anxiety scores was not affected by participation. Patient attendance at the breast multidisciplinary meeting was shown to be potentially acceptable to both patients and health professionals, without unduly raising patient anxiety. A national survey exploring attitudes towards patient involvement in the multidisciplinary team meeting is currently in progress.

Adult↗
PubMed2006

A novel luminescent lifetime-based optrode for the detection of gaseous and dissolved oxygen utilising a mixed ormosil matrix containing ruthenium (4,7-diphenyl-1,10-phenanthroline)3Cl2 (Ru.dpp).

A novel luminescent lifetime optrode is presented for the detection of gaseous and dissolved oxygen. The optrode utilises ruthenium (4,7-diphenyl-1,10-phenanthroline)(3)Cl(2) as the sensing fluorophore immobilised in a hydrophobic ormosil matrix. The ormosil matrix is synthesised at room temperature from octyltriethoxysilane and methyltriethoxysilane precursors. Investigations of different ormosils were conducted and the most effective one was selected for optrode production. Optrodes were tested for responses to gaseous and dissolved oxygen. Their responses were modelled using traditional two-site or two-exponential methods and feed-forward artificial neural networks. Comparison of the two modelling methodologies is presented and further improvements in modelling and ormosil design are suggested.

Chlorides↗
PubMed2006

Head and neck squamous cell carcinoma transcriptome analysis by comprehensive validated differential display.

Head and neck squamous cell carcinoma (HNSCC) is common worldwide and is associated with a poor rate of survival. Identification of new markers and therapeutic targets, and understanding the complex transformation process, will require a comprehensive description of genome expression, that can only be achieved by combining different methodologies. We report here the HNSCC transcriptome that was determined by exhaustive differential display (DD) analysis coupled with validation by different methods on the same patient samples. The resulting 820 nonredundant sequences were analysed by high throughput bioinformatics analysis. Human proteins were identified for 73% (596) of the DD sequences. A large proportion (>50%) of the remaining unassigned sequences match ESTs (expressed sequence tags) from human tumours. For the functionally annotated proteins, there is significant enrichment for relevant biological processes, including cell motility, protein biosynthesis, stress and immune responses, cell death, cell cycle, cell proliferation and/or maintenance and transport. Three of the novel proteins (TMEM16A, PHLDB2 and ARHGAP21) were analysed further to show that they have the potential to be developed as therapeutic targets.

Amino Acid Sequence↗
PubMed2006

Extensive DNA methylation in normal colorectal mucosa in hyperplastic polyposis.

BACKGROUND: Hyperplastic polyposis of the colorectum is a precancerous condition that has been linked with DNA methylation. The polyps in this condition have been distinguished from typical small hyperplastic polyps and renamed sessile serrated adenomas. Sessile serrated adenomas also occur sporadically and appear to be indistinguishable from their counterparts in hyperplastic polyposis. AIMS AND METHODS: The existence of distinguishing molecular features was explored in a series of serrated polyps and matched normal mucosa from patients with and without hyperplastic polyposis by assessing mutation of BRAF, DNA methylation in 14 markers (MINTs 1, 2 and 31, p16, MGMT, MLH1, RASSF1, RASSF2, NORE1 (RASSF5), RKIP, MST1, DAPK, FAS, and CHFR), and immunoexpression of MLH1. RESULTS: There was more extensive methylation in sessile serrated adenomas from subjects with hyperplastic polyposis (p<0.0001). A more clearcut difference in patients with hyperplastic polyposis was the finding of extensive DNA methylation in normal mucosa from the proximal colon. CONCLUSIONS: A genetic predisposition may underlie at least some forms of hyperplastic polyposis in which the earliest manifestation may be hypermethylation of multiple gene promoters in normal colorectal mucosa. Additionally, some of the heterogeneity within hyperplastic polyposis may be explained by different propensities for MLH1 inactivation within polyps.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Calcium sensitivity of vasospastic basilar artery after experimental subarachnoid hemorrhage.

Arteries that develop vasospasm after subarachnoid hemorrhage (SAH) may have altered contractility and compliance. Whether these changes are due to alterations in the smooth muscle cells or the arterial wall extracellular matrix is unknown. This study elucidated the location of such changes and determined the calcium sensitivity of vasospastic arteries. Dogs were placed under general anesthesia and underwent creation of SAH using the double-hemorrhage model. Vasospasm was assessed by angiography performed before and 4, 7, or 21 days after SAH. Basilar arteries were excised from SAH or control dogs (n = 8-52 arterial rings from 2-9 dogs per measurement) and studied under isometric tension in vitro before and after permeabilization of smooth muscle with alpha-toxin. Endothelium was removed from all arteries. Vasospastic arteries demonstrated significantly reduced contractility to KCl with a shift in the EC(50) toward reduced sensitivity to KCl 4 and 7 days after SAH (P < 0.05, ANOVA). There was reduced compliance that persisted after permeabilization (P < 0.05, ANOVA). Calcium sensitivity was decreased during vasospasm 4 and 7 days after SAH, as assessed in permeabilized arteries and in those contracted with BAY K 8644 in the presence of different concentrations of extracellular calcium (P < 0.05, ANOVA). Depolymerization of actin with cytochalasin D abolished contractions to KCl but failed to alter arterial compliance. In conclusion, it is shown for the first time that calcium sensitivity is decreased during vasospasm after SAH in dogs, suggesting that other mechanisms are involved in maintaining the contraction. Reduced compliance seems to be due to an alteration in the arterial wall extracellullar matrix rather than the smooth muscle cells themselves because it cannot be alleviated by depolymerization of smooth muscle actin.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2006

High-level expression, activation, and subcellular localization of p38-MAP kinase in thyroid neoplasms.

The p38 family of MAP kinases (p38-MAPKs) is involved in regulating the proliferation, survival, and migration of various cancer cells. The present study has investigated the expression, subcellular localization, phosphorylation, and activity of p38-MAPKs in normal and tumoural human thyroid tissues and in thyroid cell lines. The expression and nucleo-cytosolic compartmentalization of the alpha-isoform of p38-MAPKs (p38alpha-MAPK) were studied by western blotting in the WRO and B-CPAP cell lines, which are derived from human follicular and papillary thyroid carcinomas, respectively, and in the non-transformed rat thyroid cell lines FRTL-5 and PCCL3. Immunohistochemistry was used to study the expression and subcellular localization of p38alpha-MAPK, and of the phosphorylated forms of p38-MAPKs (P-p38-MAPKs) in human toxic adenomas (TAs), follicular adenomas (FAs), papillary thyroid carcinomas (PTCs), and follicular thyroid carcinomas (FTCs). The activity of p38-MAPKs in PTCs and FTCs was revealed by immunohistochemical detection of their typical phosphorylated substrate, MAPK-activated protein kinase 2/3 (MK2/3). p38alpha-MAPK was expressed in all cell lines and this expression was restricted to the cytosolic compartment. p38 MAPK activity was involved in regulating DNA synthesis in B-CPAP cells. p38alpha-MAPK and P-p38-MAPKs were strongly expressed in PTC and FTC cells, although only in the cytoplasm, whereas they were only very weakly expressed in FA cells, and absent in adjacent normal tissues. They were also expressed at a high level in TAs, but they were found in both nucleus and cytoplasm. Finally, phospho-MK2/3 immunostaining followed very similar patterns to those of p38alpha-MAPK and P-p38-MAPKs in PTCs and FTCs. Taken together, these results show for the first time that the p38-MAPK signalling cascade is functional in two types of differentiated carcinoma of the thyroid. The observation that p38-MAPK hyper-expression occurs in FTC, but not in FA, may provide an additional diagnostic tool for malignancy in some thyroid nodules.

Adenocarcinoma, Follicular↗
PubMed2006

Expression of the mouse fragilis gene products in immune cells and association with receptor signaling complexes.

The mouse genome possesses five genes encoding proteins homologous to human Leu-13. The Leu-13 protein associates with immune cell receptor activation complexes: a monoclonal antibody against Leu-13 induces T and B cells to form homotypic aggregates, inhibits activation-induced proliferation and induces the shedding of L-selectin. The mouse fragilis proteins have not been previously analyzed as components of the immune response. Antibody and nucleic acid reagents were generated that are specific for each of the five fragilis gene products. Expression of some of these genes (fragilis and fragilis3) is wide spread in a variety of mouse immune (and nonimmune) tissues while others (fragilis5) appear to be much more restricted. These proteins have been predicted to span the membrane twice with both amino- and carboxyl-terminal sequences extracellular: we show that a highly conserved loop of the protein between the transmembrane domains is intracellular. The fragilis proteins are associated with tetraspanin proteins CD81 and CD9: B cell activation positions fragilis into lipid rafts along with the CD81, CD19, and CD21. The mouse functional equivalent to human Leu-13 may not be single gene product, but instead may require the contribution of multiple fragilis proteins.

Amino Acid Sequence↗
PubMed2006

Factors influencing discharge location following high lesion spinal cord injury rehabilitation in British Columbia, Canada.

STUDY DESIGN: Retrospective chart review. OBJECTIVE: To identify and describe factors that influence discharge location -- extended care unit (nursing home) or other (private home, group home, or acute care) -- following rehabilitation for individuals with a new high lesion spinal cord injury (SCI) (C1-C4) in British Columbia, Canada. SETTING: GF Strong Rehabilitation Centre, Vancouver, British Columbia, Canada. METHODS: Eligible clients were adults admitted to the GF Strong Rehabilitation Centre Spinal Cord Program between 1994 and 2003, with a new C1-4 lesion (traumatic or nontraumatic), and an ASIA score of A-C at time of discharge. Medical charts of 52 individuals were reviewed and data regarding individual characteristics, health-related characteristics, personal context, hospitalization factors, health resources, and other contextual factors were extracted. RESULTS: In total, 40% of clients were discharged to extended care units post rehabilitation. Seven variables were associated at a univariate level: age, employment at the time of injury, pre-existing medical conditions, social support, preinjury living situation, and insurance (worker's compensation or motor vehicle) or private funding for equipment. Four variables were associated at the multivariate level: age, preinjury living situation, and insurance or private funding for equipment. CONCLUSION: A range of individual, health-related, family and social policy variables influence discharge location following rehabilitation for high lesion SCI in British Columbia. The unique combination of variables presented by each individual should be considered by the rehabilitation team in the discharge planning process.

Adult↗
PubMed2006

Advanced colorectal polyps with the molecular and morphological features of serrated polyps and adenomas: concept of a 'fusion' pathway to colorectal cancer.

AIM: To establish and explain the pattern of molecular signatures across colorectal polyps. METHODS AND RESULTS: Thirty-two sessile serrated adenomas (SSA), 10 mixed polyps (MP), 15 traditional serrated adenomas (SA), 49 hyperplastic polyps (HP) and 84 adenomas were assessed for mutation of KRAS and BRAF and aberrant expression of p53. The findings were correlated with loss of expression of O-6-methylguanine DNA methyltransferase (MGMT). KRAS mutation occurred more frequently (26.5%) than BRAF mutation (4.8%) in adenomas (P < 0.001) and particularly in adenomas with villous architecture (50%). Loss of expression of MGMT correlated with KRAS mutation in small tubular adenomas (P < 0.04). BRAF mutation was frequent in HPs (67%) and SSAs (81%), while KRAS mutation was infrequent (4% and 3%, respectively). Of MPs and SAs, 72% had either BRAF or KRAS mutation. Aberrant expression of p53 was uncommon overall, but occurred more frequently in MPs and SAs (12%) than adenomas (1%) (P < 0.04) and there was concordant loss of expression of MGMT. CONCLUSIONS: Molecular alterations that are characteristic of the serrated pathway and adenoma-carcinoma sequence can co-occur in a minority of advanced colorectal polyps that then show morphological features of both pathways. These lesions account for only 2% of colorectal polyps, but may be relatively aggressive.

Adenoma↗
PubMed2006

A measure of food seeking in individuals with Prader-Willi syndrome.

BACKGROUND: Individuals with Prader-Willi syndrome (PWS), a chromosome 15 genetic disorder, often have a significant preoccupation with food and problem behaviour related to food seeking is often prevalent. METHODS: In the present study, we compared how individuals with PWS responded on a survey regarding the acceptability of food in various locations that varied according to degree of appropriateness for human consumption (e.g. food on a plate, food in a garbage can). For a subgroup of participants, we observed how they actually responded when placed in a room with food items placed in the same locations depicted in the survey. In the first part of the study, three groups (25 typically developing individuals, 7 individuals with intellectual disability (ID), and 19 individuals with PWS) responded to a visual survey to determine the degree of acceptability of food items in various locations (e.g. on a table near a hairbrush, on the floor behind a toy box, in a trash can). In the second part of the study, these food items (popcorn, jelly beans) were placed in the 12 locations described above. Nine individuals diagnosed with PWS (deletion type) and three individuals with ID were given some break time in the room for 15 min. The amount of food consumed, the time spent food seeking, and time spent interacting with materials were measured. RESULTS: Results of the survey indicated that the PWS group differed significantly with regard to how they responded on the survey from the typically developing group, but did not differ significantly from the ID group. Results of the food seeking observations indicated that only three individuals with PWS ate a significant number of items. The three individuals did not differ from the rest of the group according to IQ or compulsivity score; however, they had significantly lower body mass index (BMI) scores and were younger than the other participants. CONCLUSIONS: The findings from the survey indicate that individuals with PWS are able to discriminate the appropriateness of eating items in more or less contaminated areas; however, the amount of time spent seeking food and the amount of food covertly consumed appeared to depend more directly on age and BMI.

Adolescent↗
PubMed2006

Improving the management and referral of patients with transient ischaemic attacks: a change strategy for a health community.

PROBLEM: Rapid referral and management of patients with transient ischaemic attacks is a key component in the national strategy for stroke prevention. However, patients with transient ischaemic attacks are poorly identified and undertreated. DESIGN AND SETTING: Before and after evaluation of quality improvement programme with controlled comparison in three primary care trusts reflecting diverse populations and organisational structures in an urban district in the North of England. KEY MEASURES FOR IMPROVEMENT: The proportion of patients receiving antiplatelet drugs and safe driving advice on referral to a specialty clinic, and the numbers of referrals, adjusted for age, to the specialist clinic before and after the improvement programme. STRATEGIES FOR CHANGE: Interviews with patient and professionals to identify gaps and barriers to good practice; development of evidence based guidelines for the management of patients with transient ischaemic attacks; interactive multidisciplinary workshops for each primary care trust with feedback of individual audit results of referral practice; outreach visits to teams who were unable to attend the workshops; referral templates and desktop summaries to provide reminders of the guidelines to clinicians; incorporation of standards into professional contracts. EFFECTS OF CHANGE: A significant improvement occurred in identification and referral of patients with transient ischaemic attacks to specialist clinics, with a 41% increase in referrals from trained practices compared with control practices. There were also significant improvements in the early treatment and safety advice provided to patients before referral. LESSONS LEARNT: A strategic approach to effective quality improvement across a diverse health community is feasible and achievable. Careful planning with patient and professional involvement to develop a tailored and multifaceted quality improvement programme to implement evidence based practice can work in very different primary care settings. Key components of the effectiveness of the model include contextual analysis, strong professional support, clear recommendations based on robust evidence, simplicity of adoption, good communication, and use of established networks and opinion leaders.

Communication↗
PubMed2005

Closer to an ideal solution for inguinal hernia repair: comparison between general surgeons and hernia specialists.

BACKGROUND: It is accepted a priori that specialists of hernia surgery have better results than general surgeons who use the same or different techniques as part of their complete surgical repertoire. METHODS: Results of general surgeons trained in the technique of hernia repair using a bilayer connected mesh device (BCMD) was compared to results of specialists and other general surgeons who used other techniques. RESULTS: One report from hernia specialists and three additional reports from trained general surgeons showed similar results using a BCMD. These results were better than results of all other mesh repairs. DISCUSSION: This study shows the value of surgeon-training as well as the value in the design of a particular mesh device for hernia repair. The three components of this device offer three separate, yet connected, barriers to the formation of a recurrent hernia. CONCLUSION: General surgeons trained to use a bilayer mesh device repeatedly duplicated the results of specialists who used it.

General Surgery↗
PubMed2005

What do we know about how to do audit and feedback? Pitfalls in applying evidence from a systematic review.

BACKGROUND: Improving the quality of health care requires a range of evidence-based activities. Audit and feedback is commonly used as a quality improvement tool in the UK National Health Service [NHS]. We set out to assess whether current guidance and systematic review evidence can sufficiently inform practical decisions about how to use audit and feedback to improve quality of care. METHODS: We selected an important chronic disease encountered in primary care: diabetes mellitus. We identified recommendations from National Institute for Clinical Excellence (NICE) guidance on conducting audit and generated questions which would be relevant to any attempt to operationalise audit and feedback in a healthcare service setting. We explored the extent to which a systematic review of audit and feedback could provide practical guidance about whether audit and feedback should be used to improve quality of diabetes care and, if so, how audit and feedback could be optimised. RESULTS: National guidance suggests the importance of securing the right organisational conditions and processes. Review evidence suggests that audit and feedback can be effective in changing healthcare professional practice. However, the available evidence says relatively little about the detail of how to use audit and feedback most efficiently. CONCLUSION: Audit and feedback will continue to be an unreliable approach to quality improvement until we learn how and when it works best. Conceptualising audit and feedback within a theoretical framework offers a way forward.

Humans↗
PubMed2005

Primary stenting versus primary balloon angioplasty for treating acute myocardial infarction.

BACKGROUND: Balloon angioplasty following myocardial infarction (MI) reduces death, non-fatal MI and stroke compared to thrombolytic reperfusion. However up to 50% of patients experience restenosis and 3% to 5% recurrent myocardial infarction. Therefore, primary stenting may offer additional benefits compared to balloon angioplasty in patients with acute myocardial infarction. OBJECTIVES: To examine whether primary stenting compared to primary balloon angioplasty reduces clinical outcomes in patients with acute myocardial infarction. SEARCH STRATEGY: We searched MEDLINE, EMBASE, Pascal, Index medicus and The Cochrane Controlled Trials Register (The Cochrane Library) from 1979 to March 2002. SELECTION CRITERIA: Randomised controlled trials of primary stenting or balloon angioplasty prior to the invasive procedure; intervention in native coronary arteries within 24 hours after onset of symptoms of myocardial infarction; report of death or reinfarction; and follow-up of at least 1 month. Trials were excluded when randomisation occurred after an invasive procedure and if they exclusively included patients with cardiogenic shock. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected and extracted data from identified trials. Outcomes included mortality, reinfarction, coronary artery bypass grafting, target vessel revascularization, need for vascular repair or blood transfusion. Peto odds ratios were calculated. To explore the stability of the overall treatment effect various sensitivity analyses were performed. MAIN RESULTS: We included nine trials of 4433 participants. Odds ratios for mortality after stenting compared to balloon angioplasty at 30 days, 6 and 12 months were 1.16 (95% CI 0.78 to 1.73), 1.27 (95% CI 0.89 to 1.83), and 1.06 (95% CI 0.77 to 1.45). At 30 days, 6 and 12 months odds ratios for reinfarction after stenting compared to balloon angioplasty were 0.52 (95% CI 0.31 to 0.87), 0.67 (95% CI 0.45 to 1.00), and 0.67 (95% CI 0.45-0.98) and odds ratio for target vessel revascularization after stenting compared to balloon angioplasty were 0.45 (95%CI 0.34 to 0.60), 0.42 (95% CI 0.35 to 0.51), and 0.47 (95% CI 0.38 to 0.57). The odds ratio for post-interventional bleeding complications after stenting compared to balloon angioplasty was 1.34 (95% CI 0.95 to 1.88; test of heterogeneity p > 0.1). AUTHORS' CONCLUSIONS: There is no evidence to suggest that primary stenting reduces mortality when compared to balloon angioplasty. Stenting seems to be associated with a reduced risk of reinfarction and target vessel revascularization, but potential confounding due to unbalanced post-interventional antithrombotic/anticoagulant therapies can not be ruled out on basis of this review.

Angioplasty, Balloon, Coronary↗
PubMed2005

Nutritional status and energy expenditure in children pre-bone-marrow-transplant.

The aims of this study were to establish the nutritional status of children pre-BMT and to determine whether predictive methods of assessing nutritional status and resting energy expenditure (REE) are accurate in this population. We analysed the body cell mass (BCM) (n=26) and REE (n=24) in children undergoing BMT. BCM was adjusted for height (BCM/HT(p)) and expressed as a Z score to represent nutritional status. To determine whether body mass index (BMI) was indicative of nutritional status in children undergoing BMT, BMI Z scores were compared to the reference method of BCM/HT(p) Z scores. Schofield predictive equations of basal metabolic rate (BMR) were compared to measured REE to evaluate the accuracy of the predictive equations. The mean BCM/HT(p) Z score for the subject population was -1.09+/-1.28. There was no significant relationship between BCM/HT(p) Z score and BMI Z score (r=0.34; P>0.05); however there was minimal difference between measured REE and predicted BMR (bias=-11+/-149 kcal/day). The results of this study demonstrate that children undergoing BMT may have suboptimal nutritional status and that BMI is not an accurate indication of nutritional status in this population. However, Schofield equations were found to be suitable for representing REE in children pre-BMT.

Adolescent↗