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Biomedical subjects

D Carroll

Publications and source records attributed to D Carroll.

At least 73 records · Page 4Linked to original sources

A selective human beta3 adrenergic receptor agonist increases metabolic rate in rhesus monkeys.

Activation of beta3 adrenergic receptors on the surface of adipocytes leads to increases in intracellular cAMP and stimulation of lipolysis. In brown adipose tissue, this serves to up-regulate and activate the mitochondrial uncoupling protein 1, which mediates a proton conductance pathway that uncouples oxidative phosphorylation, leading to a net increase in energy expenditure. While chronic treatment with beta3 agonists in nonprimate species leads to uncoupling protein 1 up-regulation and weight loss, the relevance of this mechanism to energy metabolism in primates, which have much lower levels of brown adipose tissue, has been questioned. With the discovery of L-755,507, a potent and selective partial agonist for both human and rhesus beta3 receptors, we now demonstrate that acute exposure of rhesus monkeys to a beta3 agonist elicits lipolysis and metabolic rate elevation, and that chronic exposure increases uncoupling protein 1 expression in rhesus brown adipose tissue. These data suggest a role for beta3 agonists in the treatment of human obesity.

Adipose Tissue, Brown↗

Quantitative systematic review of topically applied non-steroidal anti-inflammatory drugs.

OBJECTIVE: To review the effectiveness and safety of topical non-steroidal anti-inflammatory drugs in acute and chronic pain conditions. DESIGN: Quantitative systematic review of randomised controlled trials. DATA SOURCES: 86 trials involving 10,160 patients. MAIN OUTCOME MEASURES: Measures of treatment success approximating at least 50% reduction in pain, local and systemic adverse effects. Analysis at 1 week for acute and 2 weeks for chronic conditions with relative benefit and number needed to treat. RESULTS: In acute pain conditions (soft tissue trauma, strains, and sprains) placebo controlled trials had a relative benefit of 1.7 (1.5 to 1.9), the number needed to treat was 3.9 (3.4 to 4.4). With analysis by drug (at least three trials), ketoprofen (number needed to treat 2.6), felbinac (3.0), ibuprofen (3.5), and piroxicam (4.2) had significant efficacy. Benzydamine and indomethacin were no different from placebo. In chronic pain conditions (osteoarthritis, tendinitis) placebo controlled trials had a relative benefit of 2.0 (1.5 to 2.7); the number needed to treat was 3.1 (2.7 to 3.8). Small trials (< 40 treated patients) exaggerated effectiveness of topical non-steroidals by 33% in acute conditions but not in chronic conditions. There was no relation between trial quality and treatment effect. In both acute and chronic pain local and systemic adverse events and withdrawal from the study related to the drug had a low incidence and were no different from placebo. CONCLUSION: Topical non-steroidal anti-inflammatory drugs are effective in relieving pain in acute and chronic conditions.

Acute Disease↗

Mice lacking the murine interleukin-8 receptor homologue demonstrate paradoxical responses to acute and chronic experimental infection with Listeria monocytogenes.

In this study we demonstrate that mice which lack the murine interleukin-8 receptor homologue exhibit enhanced resistance during the early stage of infection (1-4 days after i.v. challenge with Listeria monocytogenes). This result is surprising in that interleukin-8 and other CXC chemokines are key players in the accumulation of inflammatory neutrophils, which is thought to be critical for resistance to listeriosis. Paradoxically, some of the interleukin-8 receptor knockout mice that survived acute infection with L. monocytogenes demonstrated evidence of chronic infection with L. monocytogenes.

Acute Disease↗

Endogenous monoamine oxidase A inhibitory activity (tribulin), measured in saliva, is related to cardiovascular reactivity in normal individuals.

Salivary monoamine oxidase A inhibitory activity (MAO-AI), mean arterial blood pressure (MAP) and heart rate (HR) were determined simultaneously in healthy male students (n = 13) at rest, before a mild psychological stressor, twice during the task and 18 minutes after the end of the task. The sample as a whole showed significant differences in MAP and HR across occasions (respectively, p < 0.001 for both). Salivary MAO-AI could distinguish novice and experienced game players (p < 0.02) and was consistently positively correlated with MAP (r = 0.58, p < 0.05 on occasion 2). Pre-task measures of MAO-AI for an increased sample (n = 18) were associated with higher MAP (but not HR) throughout the experiment (p < 0.05). Those subject with falling MAO-AI profiles from task to recovery showed significantly greater simultaneous decline in HR than those with a rising MAO-AI profile (p < 0.05).

Adult↗

Social psychophysiology, social circumstances, and health.

Health varies markedly with social circumstances. While we are still without a comprehensive account of the mechanisms which underlie this variation, it is clear that psychological factors are involved and that key pathways may prove to be psychophysiological. Thus, social psychophysiological research of the kind illustrated in this Special Issue is ideally placed to help unravel some of the mechanisms by which social circumstances impact on health. Nevertheless, the success of this sort of social psychophysiological enterprise most likely depends on reconceptualizing psychophysiological reactivity as a situational, or psychological exposure, concept rather than as an individual difference concept. This shifts the research goal from one of identifying individuals at risk for disease to identifying the psychological exposures that put individuals and groups at risk.

Adaptation, Psychological↗

RNA expression from a site-specific non-LTR retrotransposon microinjected into Xenopus oocytes.

Tx1L is a site-specific non-LTR retrotransposon (NLR) that has been identified in the genome of Xenopus laevis. Using microinjection into Xenopus oocytes, several aspects of RNA expression by these elements were investigated. With constructs carrying various parts of the element we saw no evidence of promoter activity, unlike what has been shown for several other elements of this class. Tx1L transcription was induced by linking a whole element to a promoter that is active in oocytes. Among the RNAs produced, about half had 3' ends located near the end of the element, suggesting that instruction for 3' end formation are encoded in the element or its target. Deletion of the 3' UTR of Tx1L and of surrounding target sequences indicated that these regions are not required for termination or processing of the RNA. PolyA or very A-rich sequences were added at these 3' ends, despite the absence of canonical polyA addition signals. A significant proportion of non-A residues was found in the 3' untemplated tails, and this is reminiscent of non-templated insertions often found at the 3' junction of new genomic copies of some NLRs.

3' Untranslated Regions↗

Relaxation techniques for acute pain management: a systematic review.

This review aims to document the effectiveness of relaxation techniques, when used alone for the management of acute pain, after surgery and during procedures. A systematic review of randomized controlled trials (RCTs) was undertaken. Seven studies involving 362 patients were eligible for this review. One hundred and fifty patients received active relaxation as the sole intervention. Reports were sought by searching MEDLINE, psycLIT, CINAHL, and the Oxford Pain Relief Database. The outcome measures used were pain and psychological factors. A meta-analysis was not possible, due to lack of primary data. Three of the seven studies demonstrated significantly less pain sensation and or pain distress in those who had relaxation. Four studies did not detect any difference. There was some weak evidence to support the use of relaxation in acute pain. However, this was not conclusive and many of both the positive and the negative studies suffered from methodological inadequacies. Well designed and executed randomized controlled trials are needed before the clinical use of relaxation in acute pain management can be firmly underpinned by good quality research evidence. Until this evidence is available we recommend that the clinical use of relaxation in acute pain settings is carefully evaluated and not used as the main treatment for the management of acute pain.

Acute Disease↗

Relaxation for the relief of chronic pain: a systematic review.

The effectiveness of relaxation techniques in the management of chronic pain was determined in this systematic review of published randomized controlled trials. Reports were sought by searching MEDLINE, psycLIT, CINAHL, EMBASE and the Oxford Pain Relief Database. Studies were included in this review if they were randomized controlled trials of relaxation techniques in chronic pain. Studies which investigated the effects of relaxation in combination with other interventions were not considered. Nine studies involving 414 patients met the predefined inclusion criteria and are critically appraised in this review. Meta-analysis was not possible, due to lack of quantitative data in the primary studies. Studies involved patients with a range of chronic pain conditions. The McGill Pain Questionnaire was the most common pain outcome used. Whilst four studies were able to show a significant difference for the pain outcomes in favour of relaxation for the pre- and post-treatment assessments, few statistically significant differences were reported in favour of relaxation when between treatment comparisons were used. Only three studies reported statistically significant differences in favour of relaxation (judged as a significant difference for at least 1 of the pain outcomes) compared to the other treatment groups. In rheumatoid arthritis the McGill Pain Questionnaire scores were significantly lower for patients receiving relaxation compared to those who were in the routine treatment control group. In ulcerative colitis significant differences were reported for six of seven different pain outcome measures in favour of progressive muscle relaxation compared to patients in the waiting list control group. In one of the two cancer pain studies, relaxation taught by nurses produced significantly lower pain sensation scores compared to the control group. Two studies reported significant differences in favour of the experimental control groups rather than for relaxation. There is insufficient evidence to confirm that relaxation can reduce chronic pain. Many of the studies both positive and negative suffer methodological inadequacies. Recommendations for future research into the effectiveness of relaxation techniques for chronic pain are made.

Humans↗

Comparing analgesic efficacy of non-steroidal anti-inflammatory drugs given by different routes in acute and chronic pain: a qualitative systematic review.

AIM: To test the evidence for a difference in analgesic efficacy and adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs) given by different routes. METHODS: Systematic review of published randomised controlled trials. Relevant trials were comparisons of the same drug given by different routes. Presence of internal sensitivity was sought as a validity criterion. Analgesic and adverse effect outcomes were summarised, and synthesised qualitatively. RESULTS: In 26 trials (2225 analysed patients), 8 different NSAIDs were tested in 58 comparisons. Fifteen trials (58%) compared the same drug by different routes. Drugs were given by intravenous, intramuscular, intrawound, rectal and oral routes in postoperative pain (14 trials), renal colic (4), acute musculoskeletal pain (1), dysmenorrhoea (1), and rheumatoid arthritis (6). Five of the 15 direct comparisons were invalid because they reported no difference between routes but without evidence of internal sensitivity. In all 3 direct comparisons in renal colic, intravenous NSAID had a faster onset of action than intramuscular or rectal. In 1 direct comparison in dysmenorrhoea, oral NSAID was better than rectal. In the 5 direct comparisons in postoperative pain, results were inconsistent. In 1 direct comparison in rheumatoid arthritis, intramuscular NSAID was better than oral. Injected and rectal administration had some specific adverse effects. CONCLUSION: In renal colic there is evidence that NSAIDs act quickest when given intravenously. This may be clinically relevant. In all other pain conditions there is a lack of evidence of any difference between routes. In pain conditions other than renal colic, there is, therefore, a strong argument to give oral NSAIDs when patients can swallow.

Acute Disease↗

Memorability judgments for high- and low-frequency words.

Five experiments were conducted in order to examine subjects' judgments of the memorability of high- (HF) and low-frequency (LF) words in the context of a recognition memory task. In Experiment 1, the subjects were provided study/test experience with a list of HF and LF words prior to making memorability judgments for a new list of HF and LF items. The findings were consistent with previous evidence (Greene & Thapar, 1994; Wixted, 1992) suggesting that subjects are not explicitly aware of the greater recognition memorability of LF words. Experiments 2-5 embedded the memorability judgment task within the recognition test itself. In these experiments, the subjects consistently gave higher memorability ratings to LF items. The contrast between the pattern of results found when the subjects made their judgments at the time of list presentation (Experiment 1) and that when they made their judgments during the recognition test (Experiments 2-5) is consistent with recent evidence that even seemingly highly related metamnemonic judgments (e.g., ease of learning judgments vs. judgments of learning for the same items) may be based on very different factors if they occur at different points in the study/test cycle. The present findings are also consistent with the possibility that very rapid retrieval of memorability information for HF and LF words may affect recognition decisions and may contribute to the recognition memory word frequency effect.

Analysis of Variance↗

Meeting the needs of unpartnered elders: a peer training program involving elders with myocardial infarction.

Myocardia infarction (MI) is the leading cause of death in elderly adults. For those elderly who do recover, results are less than optimal when compared to those seen with younger patients. With a shortened length of stay in hospitals for elderly MI patients, and an increase in life expectancy that leads to an estimated 33 million elders in the U.S. population, there is a growing community-based population of elders who are recovering from MI. The use of elders as peer advisors has been demonstrated to be a cost-effective method of promoting health and enhancing recovery, with only a modest investment of the professional healthcare provider's time and money. An innovative, low-cost intervention matches recent MI elders who are unpartnered--and at higher risk for morbidity and mortality than partnered elders--to a peer advisor who has also survived acute MI in the past.

Aged↗

Secretory immunoglobulin A and cardiovascular reactions to mental arithmetic and cold pressor.

Secretory immunoglobulin A (sIgA) in saliva and cardiovascular reactions to mental arithmetic and cold pressor tasks were recorded in 16 healthy young men on two sessions, 4 weeks apart. Both tasks elicited significant increases in sIgA secretion rate, reflecting increases in both salivary volume and sIgA concentration. Whereas mental arithmetic elicited a mixed pattern of alpha- and beta-adrenergic cardiovascular reactions, the pattern of reactions to cold pressor was predominantly alpha-adrenergic. Task levels of sIgA secretion rate, sIgA concentration, and saliva volume showed moderate to high test-retest reliability (r = .52-.83), although test-retest correlations were less impressive for change scores (r = -.19-.53). The pattern of correlations between change in sIgA secretion rate and cardiovascular reactivity variables was inconsistent.

Adult↗

Palliative care at home: an audit of cancer deaths in Grampian region.

BACKGROUND: Ninety per cent of the last year of life of cancer patients is spent at home. Some studies have suggested that care in this setting is often suboptimal. Information on the standard of palliative care delivered at home by general practitioners (GPs) and their teams is limited, and clarification of the problems faced is needed. AIM: To audit the home-based palliative care of patients dying of cancer. METHOD: Matched postal questionnaires were sent to the GPs and nurses of 1086 successive patients dying of cancer in whatever setting in the Grampian region of Scotland some six weeks after the death to establish the professionals' perception of symptom control, communication problems, use of services, and information given to patients and relatives. RESULTS: Response rates were 88.8% for GPs (964 out of 1086) and 87.1% for nurses (325 out of 375 that were passed on to nurses). Two-thirds of patients received palliative care at home. Pain was poorly controlled in 15.7%, and poor control of other symptoms ranged from 13.8% (nausea and vomiting) to 21% (depression and dyspnoea). Communication difficulties were present in 93.7% of cases, although only 5.2% of these were of a major nature. District nurses were involved in 76.7% of cases and Macmillan nurses in 28.0%. Twenty-six per cent of referrals to district nurses were assessed as being late in the course of the illness. Patients were fully informed about the diagnosis in 66.3% of cases and about the prognosis in 55.4%. General practitioners were more likely to report the presence of communication problems between themselves and the patient (when compared with nurses: 43.9% versus 28.0%), more likely to report that patients were 'not at all informed' about self-help groups (57.5% versus 36.3%), and were less likely to report the involvement of occupational therapists (21.8% versus 39.7%). CONCLUSIONS: Levels of reporting of poor symptom control by professionals was much lower than levels reported by relatives in other studies, but there was no difference between the reporting of GPs and nurses. However, a number of areas were identified where care could be enhanced by improved teamwork and further education and training in symptom control, as well as in communication, use of services, and information provision.

Communication↗

Thermodilution measurement of cardiac output in patients with low output: room-temperature versus iced injectate.

BACKGROUND: Measurements of cardiac output with the thermodilution technique add to data for clinical decision making and therefore must be valid and reliable. However, the results of studies on the accuracy of values obtained with room-temperature and iced injectates, especially in patients with high or low cardiac output, have been conflicting. OBJECTIVE: To determine the effect of the temperature of the injectate (iced or room temperature) on cardiac output values obtained with the thermodilution technique in critically ill adults with known low cardiac output. METHODS: A convenience sample of 50 subjects (41 men and 9 women) who had a cardiac index of less than 2.5 (calculated as cardiac output in liters per minute divided by body surface area in square meters) before the study had cardiac output measured by using a closed system and manual injections of room-temperature and iced injectates. RESULTS: A paired t test indicated no significant difference between iced and room-temperature injectates for cardiac output (iced, 3.62 L/min; room temperature, 3.71 L/min; t = 0.99; P = .327) and cardiac index (iced, 1.95; room temperature, 1.99; t = 0.71; P = .482). CONCLUSION: The findings support the practice of using room-temperature injectate to measure cardiac output in patients with low cardiac output.

Adult↗

The GTP effector site of ornithine decarboxylase from Lactobacillus 30a: kinetic and structural characterization.

A nucleotide effector site of the biodegradative form of ornithine decarboxylase from Lactobacillus 30a (OrnDC L30a) has been identified. OrnDC L30a activity at pH 8.0, where the enzyme is normally inactive, is stimulated by GTP and dGTP and to a lesser extent by GDP but not by ATP, CTP, or UTP. The pH profile indicates that activation by GTP is reflected by an increase in kcat/KM,orn (above pH 6.8), while Vmax remains constant over the pH range 4.0-9. 0. Scatchard plot analysis shows that GTP binds to OrnDC L30a at both pH 5.8 (KD = 0.11 microM) and pH 8.0 (KD = 1.6 microM), but unexpectedly, half-site binding is observed at the higher pH. The OrnDC L30a dodecamer dissociates into dimers at high pH in the presence or absence of GTP. The GTP binding site was located in difference electron density maps using low-resolution X-ray data. This represents a new type of GTP binding site. A model explaining the activation of OrnDC L30a by GTP is presented.

Bacterial Proteins↗

Ribonucleoprotein formation by the ORF1 protein of the non-LTR retrotransposon Tx1L in Xenopus oocytes.

The Tx1L elements constitute a family of site-specific non-LTR retrotransposons found in the genome of the frog Xenopus laevis . The elements have two open reading frames (ORFs) with homology to proteins of retroviruses and other retroelements. This study demonstrates an expected activity of one of the element-encoded proteins. The RNA binding properties of ORF1p, the product of the first ORF of Tx1L, were examined after expression from RNA injected into Xenopus oocytes. Using sucrose gradient sedimentation and non-denaturing gel electrophoresis, we show that ORF1p associates with RNA in cytoplasmic ribonucleoprotein (RNP) particles. Discrete RNPs are formed with well-defined mobilities. The ORF1p RNPs are distinct from endogenous RNPs that contain stored oocyte mRNAs and two specific endogenous mRNAs do not become associated with ORF1p. ORF1p appears to be capable of associating with its own mRNA and with other injected RNAs, independent of specific recognition sequences. Although nuclear localization of ORF1p was anticipated, based both on the supposed mechanism of transposition and on the presence of a potential nuclear localization signal, no significant fraction of the protein was found in the oocyte nucleus. Nonetheless, the RNA binding capability of ORF1p is consistent with the proposed model for transposition of non-LTR retrotransposons.

Animals↗

Insulin for overseas.

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Blood Glucose Self-Monitoring↗