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Biomedical subjects

C Cunningham

Publications and source records attributed to C Cunningham.

At least 19 recordsLinked to original sources
PubMed2007

Behavioural disturbance triggers recognition of dementia by family informants.

OBJECTIVE: To determine the frequency of unrecognised dementia in a group of community dwelling elderly, and to identify factors associated with dementia recognition by informants. SAMPLE SELECTION: People over 65 years with an AGECAT case or subcase organic diagnosis or an MMSE < or = 23 were identified from a database of community dwelling elderly. A psychiatrist to confirm the diagnosis of dementia according to ICD-10 criteria interviewed these individuals. STUDY PARTICIPANTS: Sixty-two community dwelling elderly meeting ICD-10 criteria for dementia whom had reliable informants. METHODS: Prior to the start of the interview the informant was questioned about whether they felt the patient had memory difficulties and if so whether they had a medical evaluation for their memory problems. A psychiatrist then interviewed the patient and informant to establish whether that patient met ICD-10 criteria for dementia. Basic sociodemographic details were collected and the following assessments were carried out: the Blessed Dementia Rating Scale, the Clinical Dementia Rating Scale, the Behave-AD and the Baumgarten Behavioural Disturbance Scale. ANALYSIS: Univariate and step-wise forward logistic regression analysis were used to examine the factors associated with recognition of memory difficulties. RESULTS: Twenty-nine percent of family informants of people with dementia failed to recognise a problem with their relatives'memory. Where memory difficulties were recognised only 39% of this group received a medical evaluation. Using univariate analysis recognition of memory difficulties by family informants was associated higher levels of behaviour disturbance ( p = or < 0.0011), greater functional impairment ( p = 0.0039), with increasing cognitive impairment ( p = 0.013). Using a logistic regression model, to test the independence of these variables, increasing behavioural disturbance (p = 0.0001) was associated with recognition of dementia by family informants. CONCLUSIONS: Recognition of memory problems by family members is associated with increasing behavioural disturbance. Even with recognition of dementia, families often fail to seek medical attention. Education of the lay public on the early signs and symptoms of dementia must be a key first step in improving recognition of dementia in the community dwelling elderly.

Activities of Daily Living↗
PubMed2006

Low back pain and occupation among Irish health service workers.

BACKGROUND: The health services sector has been identified as a high-risk work sector for low back pain (LBP) and related absenteeism. AIMS: To establish levels and predictors of LBP prevalence and associated sick leave among health service workers. To identify if levels of LBP or related absenteeism differ between occupational groups. METHODS: A postal survey using a standardized questionnaire and disproportionate random sampling of occupational groups was conducted at a single Dublin hospital. Overall hospital LBP prevalence and sickness absence were calculated using weighted analysis methods. Univariate analysis included the use of Chi-square, Fisher's exact and Mann-Whitney tests. Multivariate logistic regression techniques were used to explore for independent predictors of lifetime LBP prevalence and LBP-related sickness absence. RESULTS: An overall response rate of 62% (n = 246) was achieved. Lifetime, annual and point prevalence rates for the hospital employees were calculated at 46, 30 and 15.5%, respectively. No significant difference in prevalence was found between occupational groups but sick leave did differ with the highest level among general support and nursing staff. Multivariate analysis confirmed that occupation was an independent predictor for LBP-related sick leave (P < 0.05). CONCLUSIONS: LBP prevalence rates did not differ significantly between occupational groups but occupation was found to be an independent predictor of LBP-related sick leave. Involvement in manual handling did not predict either LBP or related sick leave.

Absenteeism↗
PubMed2006

Randomized clinical trial of botulinum toxin plus glyceryl trinitrate vs. botulinum toxin alone for medically resistant chronic anal fissure: overall poor healing rates.

PURPOSE: This study was designed to assess whether addition of glyceryl trinitrate to botulinum toxin improves the healing rate of glyceryl trinitrate-resistant fissures over that achieved with botulinum toxin alone. METHODS: Patients were randomized between botulinum toxin plus glyceryl trinitrate (Group A) and botulinum toxin plus placebo paste (Group B). Patients were seen at baseline, four and eight weeks, and six months. The primary end point was fissure healing at eight weeks. Secondary end points were symptomatic relief, need for surgery, side effects, and reduction in maximum resting and squeeze pressures. RESULTS: Thirty patients were randomized. Two-thirds of patients had maximum anal resting pressures below or within the normal range at entry to the study. Healing rates in both treatment groups were disappointing. There was a nonsignificant trend to better outcomes in Group A compared with Group B in terms of fissure healing (47 vs. 27 percent), symptomatic improvement (87 vs. 67 percent), and resort to surgery (27 vs. 47 percent). CONCLUSIONS: There is some evidence to suggest that combining glyceryl trinitrate with botulinum toxin is superior to the use of botulinum toxin alone for glyceryl trinitrate-resistant anal fissure. The poor healing rate may reflect the fact that many of the patients did not have significant anal spasm at trial entry.

Adult↗
PubMed2006

Technical report: Magnetic resonance direct thrombus imaging at 3 T field strength in patients with lower limb deep vein thrombosis: a feasibility study.

AIM: To investigate the feasibility of imaging lower limb deep vein thrombosis using magnetic resonance imaging (MRI) at 3.0 T magnetic field strength with an optimized a T1 magnetization prepared rapid gradient echo technique (MP-RAGE) in patients with normal volunteers as controls. MATERIALS AND METHODS: Patients with deep vein thrombosis (n = 4), thrombophlebitis (n = 2) and healthy volunteers (n = 9) were studied. MRI of the distal thigh and upper calf was performed at 3.0 T with MP-RAGE using two pre-pulses to suppress blood and fat (flip angle 15 degrees, echo time 5 ms, and repetition time 10 ms). A qualitative analysis was performed for detection of thrombi and image quality. Contrast-to-noise ratios were determined in thrombosed and patent veins. RESULTS: Thrombi were clearly visible as high-signal intensity structures with good suppression of the anatomical background. A blinded reader accurately diagnosed 15 out of 16 cases. The contrast-to-noise ratio measurements showed a positive contrast of thrombus over background muscle 16.9 (SD 4.3, 95% CI: 12.5-21.3) and a negative contrast of the lumen to muscle in patent veins of normal volunteers -7.8 (SD 4.3, 95% CI: -11.1 to -4.5), with p = 0.0015. CONCLUSION: Thrombi generate high signal intensity at 3.0 T allowing for their direct visualization if flowing blood, stationary blood and fat are sufficiently suppressed. This preliminary data supports the development of these techniques for other vascular applications.

Adult↗
PubMed2006

Manufacture and acoustical characterisation of a high-frequency contrast agent for targeting applications.

The aim of this study was to develop and acoustically to optimise an ultrasonic contrast agent for research imaging applications at 40 MHz. A range of liposomal dispersions were manufactured and the mean backscatter power was measured using a Boston Scientific ClearView Ultra intravascular scanner with a 40 MHz, 2.5 Fr Atlantis SR Plus catheter. The scanner had been modified to allow access to the unprocessed ultrasound data, which were digitised, and the mean backscatter power was calculated over a region-of-interest centred at 2 mm from the transducer. Mean backscatter power was normalised to the data collected from a water-air interface. The effects of sonication and rapid shaking on six liposomal samples were also studied and this indicated that both techniques significantly reduced the size of the liposomes within the dispersions. Maximum mean backscatter power was measured for sonicated liposomal dispersions with 60% by weight of phosphatidylethanolamine. Moreover, this dispersion had greater mean backscatter power than sheep blood at 40 MHz.

Contrast Media↗
PubMed2006

Importance of clinical features in diagnosis of mumps during a community outbreak.

Eleven patients with classical clinical features of mumps presented to one practice over a three month period. Initial laboratory testing for mumps virus specific IgM was positive in only two of the eleven cases. On subsequent testing by an additional system, four additional cases were IgM positive. Five were IgM negative by both assays. Some currently used serological tests for diagnosis of mumps virus infection may be negative in a high proportion of patients with clinically apparent mumps. This series illustrates that the time during the acute illness at which testing is performed may be important and that isolated serological tests cannot be relied upon to exclude a clinical diagnosis of mumps.

Adult↗
PubMed2005

Cloning and expression of TNF-alpha, IL-1beta and COX-2 in an anadromous and landlocked strain of Atlantic salmon (Salmo salar L.) during the smolting period.

The parr-smolt transformation involves complex modulation of immune parameters, affecting both cell populations and humoral factors. The expression of cytokines was studied in salmon cells and tissues during this period using an anadromous and a landlocked freshwater resident dwarf strain of Atlantic salmon (Salmo salar L.). The constitutive activity of three immunoregulatory genes encoding the cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) and the cyclo-oxygenase (COX) isoform COX-2 was investigated in head kidney, spleen and gill tissue from healthy, unvaccinated fish by real-time PCR. The TNF-alpha gene was generally lower expressed than COX-2 and IL-1beta1, which were approximately expressed at equal levels and constitutive expression was seen for COX-2 and IL-1beta1 in all tissues examined and at all sampling dates. The expression of all three genes in head kidney and spleen tissue seemed to be highest at the sampling in May for both strains around the time of seawater transfer suggesting an influence of smolting related hormones on cytokine expression. The gill tissue experienced the highest expression of IL-1beta1 and COX-2 at all sampling dates indicating that this organ is immunologically important.

Animals↗
PubMed2005

Retrofitting houses with insulation to reduce health inequalities: aims and methods of a clustered, randomised community-based trial.

This paper describes the purpose and methods of a single-blinded, clustered and randomised trial of the health impacts of insulating existing houses. The key research question was whether this intervention increased the indoor temperature and lowered the relative humidity, energy consumption and mould growth in the houses, as well as improved the health and well-being of the occupants and thereby lowered their utilisation of health care. Households in which at least one person had symptoms of respiratory disease were recruited from seven predominantly low-income communities in New Zealand. These households were then randomised within communities to receive retrofitted insulation either during or after the study. Measures at baseline (2001) and follow-up (2002) included subjective measures of health, comfort and well-being and objective measures of house condition, temperature, relative humidity, mould (speciation and mass), endotoxin, beta glucans, house dust mite allergens, general practitioner and hospital visits, and energy or fuel usage. All measurements referred to the three coldest winter months, June, July and August. From the 1352 households that were initially recruited, baseline information was obtained from 1310 households and 4413 people. At follow-up, 3312 people and 1110 households remained, an 84% household retention rate and a 75% individual retention rate. Final outcome results will be reported in a subsequent paper. The study showed that large trials of complex environmental interventions can be conducted in a robust manner with high participation rates. Critical success factors are effective community involvement and an intervention that is valued by the participants.

Adolescent↗
PubMed2005

Interventions to improve outpatient referrals from primary care to secondary care.

BACKGROUND: The primary care specialist interface is a key organisational feature of many health care systems. Patients are referred to specialist care when investigation or therapeutic options are exhausted in primary care and more specialised care is needed. Referral has considerable implications for patients, the health care system and health care costs. There is considerable evidence that the referral processes can be improved. OBJECTIVES: To estimate the effectiveness and efficiency of interventions to change outpatient referral rates or improve outpatient referral appropriateness. SEARCH STRATEGY: We conducted electronic searches of the Cochrane Effective Practice and Organisation of Care (EPOC) group specialised register (developed through extensive searches of MEDLINE, EMBASE, Healthstar and the Cochrane Library) (February 2002) and the National Research Register. SELECTION CRITERIA: Randomised controlled trials, controlled clinical trials, controlled before and after studies and interrupted time series of interventions to change or improve outpatient referrals. Participants were primary care physicians. The outcomes were objectively measured provider performance or health outcomes. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed study quality. MAIN RESULTS: Seventeen studies involving 23 separate comparisons were included. Nine studies (14 comparisons) evaluated professional educational interventions. Ineffective strategies included: passive dissemination of local referral guidelines (two studies), feedback of referral rates (one study) and discussion with an independent medical adviser (one study). Generally effective strategies included dissemination of guidelines with structured referral sheets (four out of five studies) and involvement of consultants in educational activities (two out of three studies). Three studies evaluated organisational interventions (patient management by family physicians compared to general internists, attachment of a physiotherapist to general practices and requiring a second 'in-house' opinion prior to referral), all of which were effective. Five studies (six comparisons) evaluated financial interventions. Two studies evaluating change from a capitation based to mixed capitation and fee-for-service system and from a fee-for-service to a capitation based system (with an element of risk sharing for secondary care services) observed a reduction in referral rates. Modest reductions in referral rates of uncertain significance were observed following the introduction of the general practice fundholding scheme in the United Kingdom (UK). One study evaluating the effect of providing access to private specialists demonstrated an increase in the proportion of patients referred to specialist services but no overall effect on referral rates. AUTHORS' CONCLUSIONS: There are a limited number of rigorous evaluations to base policy on. Active local educational interventions involving secondary care specialists and structured referral sheets are the only interventions shown to impact on referral rates based on current evidence. The effects of 'in-house' second opinion and other intermediate primary care based alternatives to outpatient referral appear promising.

Family Practice↗
PubMed2005

Antitumor effect of beta-elemene in non-small-cell lung cancer cells is mediated via induction of cell cycle arrest and apoptotic cell death.

Beta-elemene is a novel anticancer drug, which was extracted from the ginger plant. However, the mechanism of action of beta-elemene in non-small-cell lung cancer (NSCLC) remains unknown. Here we show that beta-elemene had differential inhibitory effects on cell growth between NSCLC cell lines and lung fibroblast and bronchial epithelial cell lines. In addition, beta-elemene was found to arrest NSCLC cells at G2-M phase, the arrest being accompanied by decreases in the levels of cyclin B1 and phospho-Cdc2 (Thr-161) and increases in the levels of p27(kip1) and phospho-Cdc2 (Tyr-15). Moreover, beta-elemene reduced the expression of Cdc25C, which dephosphorylates/activates Cdc2, but enhanced the expression of the checkpoint kinase, Chk2, which phosphorylates/ inactivates Cdc25C. These findings suggest that the effect of beta-elemene on G2-M arrest in NSCLC cells is mediated partly by a Chk2-dependent mechanism. We also demonstrate that beta-elemene triggered apoptosis in NSCLC cells. Our results clearly show that beta-elemene induced caspase-3, -7 and -9 activities, decreased Bcl-2 expression, caused cytochrome c release and increased the levels of cleaved caspase-9 and poly(ADP-ribose) polymerase in NSCLC cells. These data indicate that the effect of beta-elemene on lung cancer cell death may be through a mitochondrial release of the cytochrome c-mediated apoptotic pathway.

Apoptosis↗
PubMed2005

Antiproliferative effect of beta-elemene in chemoresistant ovarian carcinoma cells is mediated through arrest of the cell cycle at the G2-M phase.

Elemene is a natural antitumor plant drug. However, the effect of elemene on cell growth in ovarian cancer is unknown. In this study, we show that beta-elemene inhibited the proliferation of cisplatin-resistant human ovarian cancer cells and their parental cells, but had only a marginal effect in human ovary cells, indicating differential inhibitory effects on cell growth between ovarian cancer cells and normal ovary cells. We also demonstrated for the first time that beta-elemene markedly enhanced cisplatin-induced growth inhibition in resistant cells compared to sensitive cells. In addition, cell cycle analysis revealed a synergistic effect of beta-elemene and cisplatin on the induction of cell cycle G2-M arrest in our resistant ovarian carcinoma cells. Furthermore, we showed that treatment of these cells with both drugs downregulated cyclin B1 and Cdc2 expression, but elevated the levels of p53, p21waf1/cip1, p27kip1 and Gadd45. Finally, the combination of beta-elemene and cisplatin was found to increase the phosphorylation of Cdc2 and Cdc25C, which leads to a reduction in Cdc2-cyclin B1 activity. These novel findings suggest that beta-elemene sensitizes chemoresistant ovarian carcinoma cells to cisplatin-induced growth suppression partly through modulating the cell cycle G2 checkpoint and inducing cell cycle G2-M arrest, which lead to blockade of cell cycle progression.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Neuropathologically distinct prion strains give rise to similar temporal profiles of behavioral deficits.

Mouse-adapted scrapie strains have been characterized by vacuolation profiles and incubation times, but the behavioral consequences have not been well studied. Here, we compared behavioral impairments produced by ME7, 79A, 22L, and 22A strains in C57BL/6J mice. We show that early impairments on burrowing, glucose consumption, nesting and open field activity, and late stage motor impairments show a very similar temporal sequence in ME7, 79A, and 22L. The long incubation time of the 22A strain produces much later impairments. However, the strains show clear late stage neuropathological differences. All strains showed clear microglial activation and synaptic loss in the hippocampus, but only ME7 and 79A showed significant CA1 neuronal death. Conversely, 22L and 22A showed significant cerebellar Purkinje neuron loss. All strains showed marked thalamic neuronal loss. These behavioral similarities coupled with clear pathological differences could serve to identify key circuits whose early dysfunction underlies the neurological effects of different prion strains.

Animals↗
PubMed2005

MCP-1 and murine prion disease: separation of early behavioural dysfunction from overt clinical disease.

Prion diseases are chronic, fatal neurodegenerative conditions of the CNS. We have investigated the role of monocyte chemoattractant protein-1 (MCP-1) in the ME7 model of murine prion disease. MCP-1 expression increased in the CNS throughout disease progression and was positively correlated with microglial activation. We subsequently compared the inflammatory response, pathology and behavioural changes in wild-type (wt) mice and MCP-1 knockout mice (MCP-1-/-) inoculated with ME7. Late-stage clinical signs were delayed by 4 weeks in MCP-1-/- mice, and survival time increased by 2-3 weeks. By contrast, early changes in affective behaviours and locomotor activity were not delayed in onset. There was also no difference in microglial activation or neuronal death in the hippocampus and thalamus of wt mice and MCP-1-/- mice. These results highlight an important dissociation between prolonged survival, early behavioural dysfunction and hippocampal/thalamic pathology when considering therapeutic intervention for human prion diseases and other chronic neurodegenerative conditions.

Animals↗
PubMed2005

Performance of young people with Down syndrome on the Leiter-R and British picture vocabulary scales.

BACKGROUND: The British picture vocabulary scales (BPVS-II) and the Leiter international performance scales (Leiter-R), both restandardised in 1997, are often used in experimental studies to match individuals with intellectual impairment. Both provide a brief measure of mental age, and cover a wide ability range using a simple format. The BPVS-II assesses verbal comprehension and the Leiter nonverbal abilities. The issue is which to choose. People with Down syndrome (DS), for example, have particular problems in language and so the BPVS may provide an underestimation of ability. METHOD: The present study investigated this by comparing the performance of 46 young people with DS (21 females, 25 males, mean age 19 years 10 months) on the BPVS-II (verbal mental age - VMA) and the Leiter-R brief IQ (nonverbal mental age - NVMA). RESULTS: Contrary to expectations VMAs were significantly higher than NVMAs (6 years 6 months and 5 years 2 months, respectively). There was a significant correlation of 0.61 between the VMA and NVMA, and both discriminated participants at all levels of ability. However, the Leiter-R brief IQ scores provided poor discrimination at the bottom end of the IQ range (IQ 36). CONCLUSION: Both the BPVS-II and the Leiter-R provide mental age equivalent scores that are useful for plotting developmental progress, although absolute mental ages may differ.

Adult↗
PubMed2005

Low dose fraction behavior of high sensitivity radiochromic film.

A high sensitivity (HS) model of radiochromic film is receiving increasing use. The film's linear sensitometric response in the range of 0.5-40 Gy would make this film an ideal candidate for complex dosimetry applications that require tissue equivalence. This study investigates the potential use for clinical dosimetry of typical radiotherapy fractions at relatively low doses (0.5-5 Gy). The experiment involved exposing 25 pre-exposed pieces of HS film to five equal fractions of doses from 0.5 to 5 Gy 24 hours apart. The cumulative dose for each film was carefully monitored and optical density measurements were used as the sole determination of film response to dose. The average behavior of the various fractionation schemes was roughly consistent with previous observations of the MD-55 radiochromic film with about twice the overall sensitivity as expected. However, at low doses and low dose increments, unexpected variations beyond a well-documented low dose nonlinearity were observed. These unexpected variations may indicate complex polymer kinetics at low doses. This type of film would require extra care beyond that described in TG-55 for accurate use at low doses or low dose fraction schemes.

Dose Fractionation, Radiation↗
PubMed2004

Structural and functional evidences for a type 1 TGF-beta sensu stricto receptor in the lophotrochozoan Crassostrea gigas suggest conserved molecular mechanisms controlling mesodermal patterning across bilateria.

The transforming growth factor beta (TGFbeta) superfamily includes bone morphogenetic proteins, activins and TGF-betasensu stricto (s.s.). These ligands have been shown to play a key role in numerous biological processes including early embryonic development and immune regulation. They transduce their signal through a hetromeric complex of type I and type II receptors. Such receptors have been identified in ecdysozoans but none have been found as yet in the other major protostomal clade, the lophotrochozoans. Here, we report the identification of the first lophotrochozoan TGFbetas.s. type I receptor (Cg-TGFbetaRI) from the mollusk Crassostrea gigas. The phylogenetic and structural analyses as well as the expression pattern during early development suggest Cg-TGFbetaRI to belong to the TGFbetas.s./activin type I receptor clade and functional studies corroborate these deductions. The use of the zebrafish embryo as a reporter organism reveals that either Cg-TGFbetaRI or its dominant negative acting truncated form, when overexpressed during gastrulation, resulted in a range of phenotypes displaying severe disturbance of anterioposterior patterning due to a strong modulation of ventrolateral mesoderm patterning. Finally, a Cg-TGFbetaRI cytokine activity during immune regulation in C. gigas has been investigated by real-time PCR in haemocytes and mantle edge during an in vivo bacterial LPS challenge. One piece of evidence from this study suggests that the molecular mechanisms controlling mesodermal patterning and some immune regulations across all bilateria could be conserved through a functional TGF-beta s.s. pathway in lophotrochozoans.

Activin Receptors, Type I↗
PubMed2004

Chronic anal fissure.

BACKGROUND: The treatment of chronic anal fissure has shifted in recent years from surgical to medical. METHODS: A Medline search of studies relevant to modern management of chronic anal fissure was undertaken. RESULTS: Traditional surgery that permanently weakens the internal sphincter is associated with a risk of incontinence. Medical therapies temporarily relax the internal sphincter and pose no such danger, but their limited efficacy has led to displacement rather than replacement of traditional surgery. Emerging medical therapies promise continued improvement and new sphincter-sparing surgery may render traditional surgery redundant. CONCLUSION: First-line use of medical therapy cures most chronic anal fissures cheaply and conveniently. The few non-responders can be targeted for sphincter assessment before traditional surgery. If the initial good results of new sphincter-sparing surgery are confirmed, it may be possible to avoid any risk of incontinence, while achieving high rates of fissure healing.

Anal Canal↗