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Biomedical subjects

G McCarthy

Publications and source records attributed to G McCarthy.

At least 19 recordsLinked to original sources
PubMed2006

EULAR evidence based recommendations for gout. Part I: Diagnosis. Report of a task force of the Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT).

OBJECTIVE: To develop evidence based recommendations for the diagnosis of gout. METHODS: The multidisciplinary guideline development group comprised 19 rheumatologists and one evidence based medicine expert, representing 13 European countries. Ten key propositions regarding diagnosis were generated using a Delphi consensus approach. Research evidence was searched systematically for each proposition. Wherever possible the sensitivity, specificity, likelihood ratio (LR), and incremental cost-effectiveness ratio were calculated for diagnostic tests. Relative risk and odds ratios were estimated for risk factors and co-morbidities associated with gout. The quality of evidence was categorised according to the evidence hierarchy. The strength of recommendation (SOR) was assessed using the EULAR visual analogue and ordinal scales. RESULTS: 10 key propositions were generated though three Delphi rounds including diagnostic topics in clinical manifestations, urate crystal identification, biochemical tests, radiographs, and risk factors/co-morbidities. Urate crystal identification varies according to symptoms and observer skill but is very likely to be positive in symptomatic gout (LR = 567 (95% confidence interval (CI), 35.5 to 9053)). Classic podagra and presence of tophi have the highest clinical diagnostic value for gout (LR = 30.64 (95% CI, 20.51 to 45.77), and LR = 39.95 (21.06 to 75.79), respectively). Hyperuricaemia is a major risk factor for gout and may be a useful diagnostic marker when defined by the normal range of the local population (LR = 9.74 (7.45 to 12.72)), although some gouty patients may have normal serum uric acid concentrations at the time of investigation. Radiographs have little role in diagnosis, though in late or severe gout radiographic changes of asymmetrical swelling (LR = 4.13 (2.97 to 5.74)) and subcortical cysts without erosion (LR = 6.39 (3.00 to 13.57)) may be useful to differentiate chronic gout from other joint conditions. In addition, risk factors (sex, diuretics, purine-rich foods, alcohol, lead) and co-morbidities (cardiovascular diseases, hypertension, diabetes, obesity, and chronic renal failure) are associated with gout. SOR for each proposition varied according to both the research evidence and expert opinion. CONCLUSIONS: 10 key recommendations for diagnosis of gout were developed using a combination of research based evidence and expert consensus. The evidence for diagnostic tests, risk factors, and co-morbidities was evaluated and the strength of recommendation was provided.

Advisory Committees↗
PubMed2006

EULAR evidence based recommendations for gout. Part II: Management. Report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT).

OBJECTIVE: To develop evidence based recommendations for the management of gout. METHODS: The multidisciplinary guideline development group comprised 19 rheumatologists and one evidence based medicine expert representing 13 European countries. Key propositions on management were generated using a Delphi consensus approach. Research evidence was searched systematically for each proposition. Where possible, effect size (ES), number needed to treat, relative risk, odds ratio, and incremental cost-effectiveness ratio were calculated. The quality of evidence was categorised according to the level of evidence. The strength of recommendation (SOR) was assessed using the EULAR visual analogue and ordinal scales. RESULTS: 12 key propositions were generated after three Delphi rounds. Propositions included both non-pharmacological and pharmacological treatments and addressed symptomatic control of acute gout, urate lowering therapy (ULT), and prophylaxis of acute attacks. The importance of patient education, modification of adverse lifestyle (weight loss if obese; reduced alcohol consumption; low animal purine diet) and treatment of associated comorbidity and risk factors were emphasised. Recommended drugs for acute attacks were oral non-steroidal anti-inflammatory drugs (NSAIDs), oral colchicine (ES = 0.87 (95% confidence interval, 0.25 to 1.50)), or joint aspiration and injection of corticosteroid. ULT is indicated in patients with recurrent acute attacks, arthropathy, tophi, or radiographic changes of gout. Allopurinol was confirmed as effective long term ULT (ES = 1.39 (0.78 to 2.01)). If allopurinol toxicity occurs, options include other xanthine oxidase inhibitors, allopurinol desensitisation, or a uricosuric. The uricosuric benzbromarone is more effective than allopurinol (ES = 1.50 (0.76 to 2.24)) and can be used in patients with mild to moderate renal insufficiency but may be hepatotoxic. When gout is associated with the use of diuretics, the diuretic should be stopped if possible. For prophylaxis against acute attacks, either colchicine 0.5-1 mg daily or an NSAID (with gastroprotection if indicated) are recommended. CONCLUSIONS: 12 key recommendations for management of gout were developed, using a combination of research based evidence and expert consensus. The evidence was evaluated and the SOR provided for each proposition.

Acute Disease↗
PubMed2006

Research priorities for nursing and midwifery in Southern Ireland.

AIM: To identify research priorities for nursing and midwifery in the Southern Health Board area in Ireland for the immediate and long term. METHOD: Ten focus groups were conducted over a 2-month period with 70 nurses and midwives working in clinical, managerial and educational roles participating. Based on focus group findings and a literature review a multi-item Likert type questionnaire was constructed and administered to 520 nurses and midwives (response rate 95%n=494). RESULTS: Research priorities were identified as: (1) impact of staff shortages on retention of RNs/RM's (80%); (2) quality of life of chronically ill patients (76%); (3) stress and bullying in the workplace (76%); (4) assessment and management of pain (75%); (5) skill mix and staff burnout (73%); (6) cardio-pulmonary resuscitation decision making (72%); (7) coordination of care between hospital and primary care settings (69%); (8) medication errors (67%); and (9) promoting healthy lifestyles (64%). Respondents also indicated that these priorities warranted immediate attention. Implications for practice include the need for: (1) emphasis on quality pain control; (2) recognition and exploration of the ethical issues relating to resuscitation; and (3) management of the context within which clinical care is given.

Attitude of Health Personnel↗
PubMed2005

Genome wide significant linkage in schizophrenia conditioning on occurrence of depressive episodes.

BACKGROUND: Schizophrenia shows substantial clinical heterogeneity. One common important clinical variable in presentation is the occurrence of episodes of major depression. METHODS: We undertook analyses in an attempt to detect loci that influence susceptibility to, or modify the clinical expression of, schizophrenia according to the occurrence of episodes of major depression. We used a logistic regression framework in which lifetime presence/absence of major depression was entered as a covariate in the linkage analysis of our UK schizophrenia affected sibling pair series (168 affected sibling pairs typed for a 10 cM map of microsatellite markers). RESULTS: Inclusion of presence/absence of depression as a covariate detected a genome wide significant linkage signal on chromosome 4q28.3 at 130.7 cM (LOD = 4.59; p = 0.038; increase in maximum LOD over univariate analysis (ILOD) = 3.62). Inclusion of the depression covariate also showed suggestive evidence of linkage on 20q11.21 (LOD = 4.10; expected to occur by chance 0.093 times per genome scan, ILOD = 2.83). CONCLUSIONS: Our findings identify loci that may harbour genes that play a role in susceptibility to, or modify the risk of, episodes of major depression in people with schizophrenia.

Analysis of Variance↗
PubMed2005

Treatment for methaqualone dependence in adults.

BACKGROUND: Methaqualone is a potent quinazoline, a class of sedative-hypnotics, that has a high potential for abuse. While the oral use of methaqualone (Quaalude, Mandrax) has waned in western countries since the mid-late 1980's, the practice of smoking methaqualone is a serious public health problem in South Africa, other parts of Africa and India. In the context of diminishing resources devoted to substance abuse treatment in regions affected by methaqualone abuse, it would be desirable to base treatment on the best evidence available. This review aimed to provide health care workers, policy-makers and consumers with the necessary information to make decisions regarding effective treatment of this highly dependence-producing drug. OBJECTIVES: To compare the effectiveness of any type of pharmacological or behavioural treatment administered in either an in-patient or out-patient setting compared with either a placebo or no treatment or a waiting list, or with another form of treatment administered in either an in- or out-patient setting. SEARCH STRATEGY: The authors searched the following databases: Cochrane Drugs and Alcohol Group'Register of Trials (February 2004); Cochrane Central Register of Controlled Trials (CENTRAL-The Cochrane Library, Issue 2, 2004); MEDLINE (OVID - January 1966 to february 2004), PsycInfo (OVID - January 1967 to february 2004). Relevant conference proceedings and reference lists of relevant articles were hand-searched. Broad internet searches were conducted and contact made with experts in the field. SELECTION CRITERIA: All randomised controlled trials and quasi-randomised trials of the effectiveness of treatment programmes (in- or out-patient) for methaqualone dependence and abuse were considered for inclusion in this review. DATA COLLECTION AND ANALYSIS: The authors independently assessed study eligibility and quality. MAIN RESULTS: No studies were found that met the inclusion criteria. AUTHORS' CONCLUSIONS: To date, no randomized controlled trials appear to have been conducted. Consequently, the effectiveness of inpatient versus outpatient treatment, psychosocial treatment versus no treatment, and pharmacological treatments versus placebo for methaqualone abuse or dependence has yet to be established.

Adult↗
PubMed2003

A systematic genomewide linkage study in 353 sib pairs with schizophrenia.

We undertook a genomewide linkage study in a total of 353 affected sib pairs (ASPs) with schizophrenia. Our sample consisted of 179 ASPs from the United Kingdom, 134 from Sweden, and 40 from the United States. We typed 372 microsatellite markers at approximately 10-cM intervals. Our strongest finding was a LOD score of 3.87 on chromosome 10q25.3-q26.3, with positive results being contributed by all three samples and a LOD-1 interval of 15 cM. This finding achieved genomewide significance (P<.05), on the basis of simulation studies. We also found two regions, 17p11.2-q25.1 (maximum LOD score [MLS] = 3.35) and 22q11 (MLS = 2.29), in which the evidence for linkage was highly suggestive. Linkage to all of these regions has been supported by other studies. Moreover, we found strong evidence for linkage (genomewide P<.02) to 17p11.2-q25.1 in a single pedigree with schizophrenia. In our view, the evidence is now sufficiently compelling to undertake detailed mapping studies of these three regions.

Genetic Linkage↗
PubMed2002

Myocarditis in sibling boxer puppies associated with Citrobacter koseri infection.

Two sibling Boxer puppies presented with severe suppurative myocarditis in the absence of additional disseminated suppurative foci. The identification of gram-negative bacteria within areas of myocarditis in both puppies and the pure growth of large numbers of Citrobacter koseri from the myocardial lesions in one of the dogs were consistent with a bacterial etiology. The fact that C. koseri is an opportunist pathogen suggested intercurrent immunosuppression. The finding of a concomitant bacterial myocarditis in two canine siblings is novel. The case is also unusual in that syncope could be related to the myocardial injury.

Animals↗
PubMed2001

Dissociating the neural mechanisms of visual attention in change detection using functional MRI.

We investigated using functional magnetic resonance imaging (fMRI) the neural processes associated with performance of a change-detection task. In this task, two versions of the same picture are presented in alternation, separated by a brief mask interval. Even when the two pictures greatly differ (e.g., as when a building is in different locations), subjects report that identification of the change is difficult and often take 30 or more seconds to identify the change. This phenomenon of "change blindness" provides a powerful and novel paradigm for segregating components of visual attention using fMRI that can otherwise be confounded in short-duration tasks. By using a response-contingent event-related analysis technique, we successfully dissociated brain regions associated with different processing components of a visual change-detection task. Activation in the calcarine cortex was associated with task onset, but did not vary with the duration of visual search. In contrast, the pattern of activation in dorsal and ventral visual areas was temporally associated with the duration of visual search. As such, our results support a distinction between brain regions whose activation is modulated by attentional demands of the visual task (extrastriate cortex) and those that are not affected by it (primary visual cortex). A second network of areas including central sulcus, insular, and inferior frontal cortical areas, along with the thalamus and basal ganglia, showed phasic activation tied to the execution of responses. Finally, parietal and frontal regions showed systematic deactivations during task performance, consistent with previous reports that these regions may be associated with nontask semantic processing. We conclude that detection of change, when transient visual cues are not present, requires activation of extrastriate visual regions and frontal regions responsible for eye movements. These results suggest that studies of change blindness can inform understanding of more general attentional processing.

Adult↗
PubMed2001

Transverse instability of vector solitons and generation of dipole arrays.

We develop a theory of modulational instability of multiparameter solitary waves and analyze the transverse instability of composite (or vector) optical solitons in a saturable nonlinear medium. We demonstrate theoretically and experimentally that a soliton stripe breaks up into an array of ( 2+1)-dimensional dipole-mode vector solitons, thus confirming the robust nature of those solitons as fundamental composite structures of incoherently coupled fields.

Journal Article↗
PubMed2001

The effects of single-trial averaging upon the spatial extent of fMRI activation.

We examined effects of trial averaging upon spatial extent, spatial topography, and temporal properties of fMRI activation. Two subjects participated in an event-related visual stimulation design. There was an exponential relation between number of trials and spatial extent, such that additional trials identified, on average, a constant proportion of the remaining voxels. At values typical of fMRI experimentation (e.g. 50 trials) only about 50% of eventually active voxels were significant; asymptotic values were approached by 150 trials. The variability of the estimated hemodynamic response decreased with signal averaging, becoming stable across samples of > or = 25 trials. Therefore, group or condition differences may result from differences in voxelwise noise exacerbated by averaging small numbers of trials.

Adult↗
PubMed2001

Eyes first! Eye processing develops before face processing in children.

Faces and eyes are critical social stimuli which adults process with ease, but how this expertise develops is not yet understood. Neural changes associated with face and eye processing were investigated developmentally using ERPs (N170), in 128 subjects (4-15 year olds and adults). Stimuli included upright faces to assess configural processing, eyes and inverted faces to assess feature-based processing. N170 was present in the youngest children with similar patterns of face sensitivity seen in adults. Development of N170 to upright faces continued until adulthood, suggesting slow maturation of configural processing. In contrast, N170 was shorter latency and much larger to eyes than faces in children and was mature by 11 years, suggesting the early presence of an eye detector, with a rapid maturational course.

Adolescent↗
PubMed2001

Inflammatory microcrystals induce murine macrophage survival and DNA synthesis.

The interaction of particulates with resident macrophages is a consistent feature in certain forms of crystal-induced inflammation, for example, in synovial tissues, lung, and the peritoneum. The mitogenic activity of basic calcium phosphate (BCP) crystals and calcium pyrophosphate dihydrate (CPPD) crystals on synovial fibroblasts has been considered relevant to the synovial hyperplasia observed in crystal-induced arthritis. The aim of the study was to determine whether microcrystals such as these could enhance macrophage survival and induce DNA synthesis, thus indicating that they may contribute to the tissue hyperplasia. Murine bone-marrow-derived macrophages were treated in vitro with microcrystals, the cell numbers were monitored over time, and DNA synthesis was measured as the incorporation of [methyl-(3)H]thymidine (TdR). We report here that BCP, monosodium urate, talc, and, to a lesser extent, CPPD crystals promote macrophage survival and DNA synthesis; the latter response is particularly striking in the presence of low concentrations of macrophage-colony stimulating factor (M-CSF, CSF-1). Enhanced macrophage survival or proliferation may contribute to the synovial hyperplasia noted in crystal-associated arthropathies, as well as to talc-induced inflammation and granuloma formation. The crystals studied join the list of particulates having these effects on macrophages, indicating the generality of this type of response.

Animals↗
PubMed2001

The effects of aging upon the hemodynamic response measured by functional MRI.

We comparedthe characteristics of the visually evoked hemodynamic response (HDR) in groups of young and elderly adults. Checkerboard stimuli were presented for 500 ms either singly or in pairs separated by a 2-s intrapair interval while gradient-echo echoplanar fMRI images were acquired concurrently every 1 s. Activated voxels, identified by correlation with an empirically derived reference waveform, were found for both groups in cortex along the calcarine sulcus and in the fusiform gyrus, with the mean HDR latency in calcarine cortex peaking approximately 300 ms earlier than the HDR evoked in the fusiform gyrus. On average, younger subjects had twice as many activated voxels as older subjects. The mean HDR had a similar onset time, rate of rise, and peak amplitude in both groups. However, the HDRs of older subjects reached their peak earlier and were more variable across subjects. Despite having average HDR amplitudes similar to those of younger subjects, older subjects had higher noise levels in activated voxels, resulting in lower signal-to-noise ratios. Distribution analyses of voxel statistics (t value, peak amplitude, peak latency) revealed that older subjects had proportionally fewer small-effect-size voxels, due to their increased voxelwise noise. This finding was consistent with the smaller spatial extent of activation in older subjects. To investigate age differences in the refractory period of the visual HDR, the HDR evoked by the second stimulus of each pair was isolated by subtracting the HDR evoked by a single stimulus from the composite HDR evoked by a pair. Recovery measures were similar across the age groups.

Adolescent↗
PubMed2001

Regional differences in the refractory period of the hemodynamic response: an event-related fMRI study.

We investigated the characteristics of the hemodynamic response (HDR) to paired presentations of visual face stimuli using functional magnetic resonance imaging (fMRI). Photographs of faces were presented singly or in pairs with either a 1-s or 6-s intrapair interval (IPI). Each trial (single face or face pairs) was followed by an intertrial interval of 16-20 s. Faces were presented at fixation and passively viewed by the 10 subjects. Images were acquired at 1.5 Tesla using a gradient-echo echo-planar imaging sequence sensitive to blood-oxygenation-level-dependent (BOLD) contrast. To examine the refractory properties of the HDR, we subtracted the single-stimulus hemodynamic response from the composite response evoked by face pairs for all voxels significantly active on single face trials. The residual represents the contribution of the second stimulus to the fMRI signal. Event-related presentation of faces evoked activity in medial calcarine cortex and the fusiform gyrus bilaterally. In both calcarine and fusiform regions, the hemodynamic response to the second face in a pair was of lower amplitude and of increased latency at 1 s IPI, with significant recovery of both amplitude and latency toward single-stimulus values at 6 s IPI. At 1 s IPI, significantly greater recovery was found in posterior fusiform regions (50-60%) than in midfusiform regions (10-40%). These regional differences were not apparent at 6 s IPI. No differences were found across slices in calcarine cortex. There was a significant difference in mean latency to HDR peak between calcarine and fusiform cortex, with the HDR peaking about 400 ms earlier in calcarine cortex. We conclude that characteristics of the HDR, notably its amplitude, latency, and refractory properties, differ across visual cortical areas.

Adult↗
PubMed2001

Association analysis of NOTCH4 loci in schizophrenia using family and population-based controls.

A genetic association between NOTCH4 and schizophrenia has previously been proposed. Unsing all markers previously shown to be associated, we found no evidence for such in three independent family-based samples (n=519 parent-offspring trios), and a case-control sample derived from the same ethnic background as the original observation. These data strongly suggest that NOTCH4 is not a significant susceptibility allele for schizophrenia.

Case-Control Studies↗