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Biomedical subjects

D Carroll

Publications and source records attributed to D Carroll.

At least 19 recordsLinked to original sources
PubMed1992

Morphine responsiveness of chronic pain: double-blind randomised crossover study with patient-controlled analgesia.

There is controversy about whether the lack of response of some chronic pain to opioid treatment is absolute or relative. It is widely believed that nociceptive pain is responsive to opioids whereas neuropathic pain tends not to be. We have used a method of patient-controlled analgesia (PCA) with simultaneous nurse-observer measurement of analgesia, mood, and adverse effects to address these issues. Ten patients with chronic pain were given morphine at two concentrations (10 and 30 mg/ml) by PCA in two separate sessions in a double-blind randomised crossover study. Before the study a clinical judgment was made as to whether each pain was nociceptive or neuropathic. Seven patients showed good analgesic responses (more than 70 mm pain relief on a visual-analogue scale) of pain at rest, two patients poor responses (less than 30 mm pain relief), and one a moderate response with both concentrations (30-70 mm pain relief). The response to morphine was consistent (greater and faster relief with the higher concentration) in nine patients. Two patients had pain on movement that responded moderately to low-concentration morphine and well to the higher concentration. All patients with pains judged to be nociceptive showed good analgesic responses compared with half of those with neuropathic pain. There was no evidence that analgesic responses in patients with neuropathic pain were due to changes in mood. This PCA method is a quick and efficient tool to determine the consistency of the analgesic response. Such consistency can guide the clinician as to whether continued or higher-dose opioid treatment will produce good analgesia. An inconsistent response points to the use of other pain-relieving strategies.

Adult↗
PubMed1992

The effects of physical activity and exercise training on psychological stress and well-being in an adolescent population.

To determine whether participating in physical activity affects psychological well-being in an adolescent population, 147 adolescents completed self-reports of exercise and psychological stress and well-being. Analysis revealed that those who reported greater physical activity also reported less stress and lower levels of depression. Adolescents who experienced a higher incidence of life events also demonstrated a strong association between stress and anxiety/depression/hostility. To investigate the effects of exercise training on psychological well-being, adolescents were assigned to either high or moderate intensity aerobic training, flexibility training or a control group. The training groups met twice per week for 25-30 min. Aerobic fitness levels, heart rate, blood pressure and self-report of stress and well-being were measured prior to and following 10 weeks of training. Post-training fitness measures confirmed the effectiveness of the high intensity aerobic exercise and between groups differences for physiological and some psychological measures were found. Subjects undergoing high intensity exercise reported significantly less stress than subjects in the remaining three groups. The relationship between stress and anxiety/depression/hostility for the high intensity group was considerably weakened at the end of the training period. For the remaining subjects, however, this relationship was, if anything, strengthened. This experiment provides evidence to suggest that in an adolescent population, high intensity aerobic exercise has positive effects on well-being.

Adaptation, Psychological↗
PubMed1992

Employment among young people with epilepsy.

The study reports the findings of a follow-up review of 38 trainees who had completed social skills training programmes run by BRAINWAVE The Irish Epilepsy Association and FAS, the state training and employment authority, during the period 1986 to 1990. The social skills programmes were aimed at young, unqualified school leavers. A total of 101 young people completed the programmes, 45 of whom had epilepsy. Of those with epilepsy, 38 were interviewed about their current employment position. On completion of the programmes 58% had found a job or gone on to further training. At the time of interview 39% were in work or training. Fifty-eight per cent were still experiencing seizures (a seizure in the last 12 months). Fifty per cent of those interviewed felt that they were being actively discriminated against because of their epilepsy. Fifty-eight per cent had made contact with the National Rehabilitation Board, the state placement service for people with a disability, but only 36% of these were in training or employment at the time of interview. Sixty-six per cent of those interviewed had found the programmes helpful in terms of increasing their self-confidence and social skills. The study points to the need for more specialized training and job placement programmes for young people with epilepsy.

Adult↗
PubMed1992

Low dose amitriptyline in the treatment of chronic pain.

The analgesic efficacy of amitriptyline 25 mg was compared with placebo in 41 patients with chronic (more than 3 months) nonmalignant pain, using a double-blind randomised multiple-dose 3-week treatment period crossover design. Amitriptyline 25 mg provided significantly greater efficacy than placebo, with significant differences evident within the first week. There was no significant difference on mood scores between amitriptyline and placebo. The results suggest that surprisingly low doses of amitriptyline may be effective without substantial adverse effects, that the effect is evident early, and that the effect is distinguishable from any effect of the amitriptyline on mood.

Adult↗
PubMed1992

A multiple dose comparison of combinations of ibuprofen and codeine and paracetamol, codeine and caffeine after third molar surgery.

In a randomised, double-blind, double-dummy, multiple dose, crossover study in 30 patients we compared an ibuprofen/codeine combination (400 mg ibuprofen/25.6 mg codeine phosphate) with a paracetamol/codeine/caffeine combination (1 g paracetamol/16 mg codeine phosphate/60 mg caffeine) for pain relief over 6 days after two-stage bilateral lower third molar removal. The ibuprofen combination produced significantly greater analgesia than the paracetamol combination, both on single-dose analysis of the first and second days and on multiple-dose measures for days 1, 2, 3 and 4. The mean incidence of adverse effects over the 6 days was 20% for both combinations. This trial design (crossover with multiple dosing in outpatients) is a sensitive way of testing for analgesia, and is potentially more predictive of adverse effect problems than single-dose studies. It confirms that multiple dosing may show increased efficacy.

Acetaminophen↗
PubMed1992

Opioid sensitivity of chronic pain: a patient-controlled analgesia method.

Twenty-two patients with chronic pain of malignant or nonmalignant origin were given intravenous morphine by patient-controlled analgesia. A prestudy judgment was made from the characteristics of the pain as to whether it was nociceptive or neuropathic. Analgesic efficacy was assessed by a nurse-observer; adverse events were noted and plasma morphine and metabolitie concentrations measured. Three categories of opioid response were distinguished. Good responders obtained > 70 mm relief on the visual analogue scale, with minimal or manageable adverse events. Moderate responders obtained < 70 but > 30 mm relief with more problematic adverse events, and poor responders had < 30 mm relief with troublesome adverse events. This method for the study of opioid sensitivity allowed a wide dosage range to be studied. The simultaneous analgesic and adverse event measurements showed that the spectrum of observed response was wide, and response category could be judged for the majority by 4 h. In those with poor or moderate response, adverse event severity limited further dose increment. The relationship between pain characteristics and response showed that some pains judged to be neuropathic had a good response to opioid (5/13), and some pains judged to be nociceptive did not (5/14). The study suggests that the pattern of response is not as black and white as the prediction of good response from nociceptive pain and poor from neuropathic pain would suggest, although nociceptive pain was more likely than neuropathic pain to show a good response. For the moderate responders opioid titration may, in the absence of other effective treatments, be useful, but the analgesic endpoint may not be totally satisfactory. The method provides an operational definition of opioid sensitivity.

Adult↗
PubMed1992

Test of the double-strand-break repair model of recombination in Xenopus laevis oocytes.

A direct test was made of predictions of the double-strand-break repair (DSBR) model of recombination in Xenopus laevis oocytes. The DNA substrate injected into oocytes had two directly repeated copies of a 1.25-kb sequence and was cleaved within one of them. Different products were expected to result from concerted, conservative events, as predicted by the DSBR model, and from nonconservative events. Only very low levels of recombination products, both conservative and nonconservative, were observed. When individual, apparent DSBR products were cloned and characterized, it emerged that the majority of them had arisen by nonconservative recombination through short, terminal homologies and not from the gene conversion events predicted for DSBR. Two cloned products among 44 tested corresponded to the predications of the DSBR model, but these could also have been generated by other processes. The most efficient recombination events in oocytes are nonconservative and are based on long, terminal homologous overlaps; when these are not available, short, imperfect overlaps support a lower level of nonconservative recombination; genuine, conservative DSBR events occur rarely, if at all.

Animals↗
PubMed1992

Effect of terminal nonhomologies on homologous recombination in Xenopus laevis oocytes.

Homologous recombination of linear DNA molecules in Xenopus laevis oocytes is very efficient. The predictions of molecular models for this recombination process were tested with substrates with terminal nonhomologies (nonhomologous sequences). It was found that nonhomologies on one or both ends of an otherwise efficient substrate substantially reduced the yield of recombination products. In the case of a single nonhomology, inhibition was observed for all lengths of nonhomology, from 60 to 1,690 bp, being most dramatic for the longer blocks. Examination of time courses of recombination showed that the blocks were largely kinetic; that is, substrates with short nonhomologies eventually yielded substantial levels of completed products. Intermediates that accumulated after the injection of end-blocked substrates were characterized by two-dimensional gel electrophoresis and hybridization with strand-specific oligonucleotide probes. These blocked intermediates were shown to have base-paired junctions, but resolution was prevented by the failure to remove the 3'-ending strand of the original nonhomology. Continuing exonuclease action created a single-strand gap adjacent to the position of the persistent nonhomology. In contrast, the strand that included the unblocked side of the junction could be sealed. These results are consistent with a nonconservative, resection-annealing mechanism of homologous recombination in the oocytes and suggest the absence of any activity that can efficiently remove 3' tails.

Animals↗
PubMed1991

Homologous recombination catalyzed by a nuclear extract from Xenopus oocytes.

Xenopus laevis oocytes efficiently recombine linear DNA injected into their nuclei (germinal vesicles). This process requires homologous sequences at or near the molecular ends. Here we report that a cell-free extract made from germinal vesicles is capable of accomplishing the complete recombination reaction in vitro. Like the in vivo process, the extract converts the overlapping ends of linear substrate molecules into covalently closed products. Establishment of this cell-free system has allowed examination of the cofactors required for recombination. The first step involves a 5'----3' exonuclease activity that requires a divalent cation but not NTPs. Completion of recombination requires a hydrolyzable NTP; maximal product formation occurs in the presence of millimolar levels of ATP or dATP. At submillimolar levels of all four dNTPs, homologous recombination is inefficient, and a side reaction produces end-joined products. This cell-free system should facilitate a step-by-step understanding of an homologous recombination pathway that operates not only in Xenopus laevis oocytes but also in cells from a wide variety of organisms.

Adenine Nucleotides↗
PubMed1991

Genetics of Type A behavior in two European countries: evidence for sibling interaction.

Young male twins in The Netherlands and England completed the Jenkins Activity Survey (Dutch and English versions, respectively), a measure of Type A behavior. Separate model fitting analysis revealed a similar pattern of variance estimates and associated goodness of fit across the two countries. The data were then analyzed concurrently, with a scalar parameter included to account for differences in variance due to the disparity of the measurement scales. A model including additive genetic and individual environmental effects gave a good explanation to the data. The heritability estimate was 0.28. Models of social interaction and dominance explained the data even better, the former being preferred. The twins' parents were included in the analysis to examine population variation for Type A behavior intergenerationally. There was evidence for individual environmental experiences having a greater influence on Type A behavior in the older generation.

Adolescent↗
PubMed1991

Stress and well-being in nurses: a comparison of the public and private sectors.

Nurses in the public and private sectors were compared with regard to occupational stress and its sources and self-reported health and well-being. While both groups reported similar high levels of stress experience, most noticeably arising from high work loads and the experience of death and dying, group differences did emerge from an examination of the sources of stress. Whereas N.H.S. nurses were more troubled by high work loads, private sector nurses reported uncertainty over treatment as a more frequent source of stress than did their N.H.S. counterparts. Levels of self-reported mental and physical health symptomatology did not differ between groups. Nevertheless, overall nursing stress scores and symptomatology were significantly correlated, and workload was the best independent predictor of health and well-being status.

Burnout, Professional↗
PubMed1991

Treating Type A behaviours and mild hypertension in middle-aged men.

Unmedicated mildly hypertensive Type A men were randomly allocated to one of three conditions: stress management intervention training (N = 15), Type A management (N = 15), and delayed Type A management intervention. Significantly greater reductions in blood pressure at rest and during the Type A structured interview were found following the active interventions than during the minimal treatment control period of the delayed intervention. Type A management was more successful in changing a number of Type A behaviours, including anger, hostility and global Type A behaviour. Changes on measures of anger-in, -out, hostility, and SI ratings of Type A behaviour were associated with changes in systolic and diastolic blood pressure reactivity during interview.

Adult↗
PubMed1991

Synthetic peptide substrates for casein kinase II.

Synthetic peptide substrates for CKII are useful reagents in the analysis of phosphorylation sites when used in conjunction with biochemical and genetic analysis of the protein substrates for the enzyme. A multidisciplinary approach should be applied to the characterization of the synthetic peptide products, including amino acid analysis, sequencing, and mass spectrometry. Synthetic procedures for CKII substrate peptides often result in anisole adducts and dehydrated forms. Mass spectrometry is invaluable in identifying these contaminants, and preparative HPLC can be used to separate them from the desired product. Quantitative analysis of the CKII phosphorylation of peptides can utilize phosphocellulose paper if the peptide has a basic sequence, or thin-layer chromatography, if the peptide has no basic portion. Qualitative analysis using electrophoresis and mass spectrometry help to establish the stoichiometry of phosphorylation. Sequence analysis of phosphoserine after beta elimination and derivatization is useful in quantifying adjacent phosphorylation sites. Overall, application of a variety of techniques permits detailed analysis of CKII phosphorylation sites on synthetic peptides that are model substrates.

Adenosine Triphosphate↗
PubMed1991

A twin study approach towards understanding genetic contributions to body size and metabolic rate.

The genetic and environmental determinants of a brief assessment of metabolic rate at rest and under psychological stress were studied in 40 pairs of monozygotic and 40 pairs of dizygotic young adult male twins. Height, weight and age were employed as covariates. Univariate analyses showed a high heritability for height and weight and moderate heritability for metabolic rate. Classical twin analyses and multivariate genetic modeling indicated that genetic influences on resting metabolic rate were entirely explained by body weight: there was no independent genetic contribution to resting metabolic rate. Metabolic rate under psychological stress, on the other hand, showed a significant genetic effect. The exponent (3/4) in the power function relating body weight to resting metabolic rate was the same as that found in a wide variety of animal species, a value that has been proposed as defining a body weight set point. We speculate that an adult body weight set point is genetically transmitted. Independent genetic effects on resting metabolic rate would be observed only when the normal equilibrium between body weight and metabolic rate is unbalanced during development, aging or disease. The study illustrates the use of multivariate genetic analyses of twin data which may be readily applied to widely used metabolic rate assessments.

Adolescent↗
PubMed1991

Haemodynamic adjustments to mental stress in normotensives and subjects with mildly elevated blood pressure.

Cardiac output, heart rate, stroke volume, pre-ejection period, total peripheral resistance, systolic and diastolic blood pressure, and oxygen consumption were monitored or derived in young men with mildly elevated casual blood pressures and unambiguously normotensive control subjects before, during, and after exposure to a mental arithmetic stress. Measurements were also taken while subjects underwent graded dynamic exercise. This permitted cardiac output-oxygen consumption regression equations to be calculated and, as a consequence, cardiac output during mental stress to be represented as additional cardiac output. Systolic and diastolic blood pressure were higher during all phases of the study in the mildly elevated blood pressure group. An overall groups effect during the mental stress phase of the experiment was observed for cardiac output and pre-ejection period, and the effect for stroke volume was close to significance. Significant Groups X Periods interactions were found for cardiac output and additional cardiac output, and the heart rate effect was nearly significant. Post-hoc comparisons here indicated that, in the main, group differences in these cardiac variables were more evident during the mental arithmetic stress than during the pre- and post-task baseline periods. Total peripheral resistance did not differ reliably between groups and the cardiac effects were specific to the mental stress phase of the study.

Adult↗
PubMed1991

Involvement of single-stranded tails in homologous recombination of DNA injected into Xenopus laevis oocyte nuclei.

Homologous recombination of DNA molecules injected into Xenopus laevis oocyte nuclei is extremely efficient when those molecules are linear and have overlapping homologous ends. It was previously shown that a 5'----3' exonuclease activity in oocytes attacks injected linear DNAs and leaves them with single-stranded 3' tails. We tested the hypothesis that such tailed molecules are early intermediates on the pathway to recombination products. Substrates with 3' tails were made in vitro and injected into oocytes, where they recombined rapidly and efficiently. In experiments with mixed substrates, molecules with 3' tails entered recombination intermediates and products more rapidly than did molecules with flush ends. Molecules endowed in vitro with 5' tails also recombined efficiently in oocytes, but their rate was not faster than for flush-ended substrates. In most cases, the 5' tails served as templates for resynthesis of the 3' strands, regenerating duplex ends which then entered the normal recombination pathway. In oocytes from one animal, some of the 5' tails were removed, and this was exacerbated when resynthesis was partially blocked. Analysis by two-dimensional gel electrophoresis of recombination intermediates from 5'-tailed substrates confirmed that they had acquired 3' tails as a result of the action of the 5'----3' exonuclease. These results demonstrate that homologous recombination in oocytes proceeds via a pathway that involves single-stranded 3' tails. Molecular models incorporating this feature are discussed.

Animals↗