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Biomedical subjects

D Carroll

Publications and source records attributed to D Carroll.

At least 91 records · Page 5Linked to original sources
PubMed1997

The effects of blood pressure resting level and lability on cardiovascular reactions to laboratory stress.

Evidence that individuals with elevated resting blood pressures display excessive cardiovascular reactions to laboratory stress is regarded as implicating excessive reactivity in the pathogenesis of hypertension. However, it remains possible that this relationship is artifactual, in that resting blood pressure levels and cardiovascular reactions might both reflect intrinsic cardiovascular lability. To examine this possibility, blood pressure and heart rate were measured at rest and in response to an active laboratory stressor in 1259 men. Systolic blood pressure and heart rate reactions to the stressor were predicted by resting blood pressure. Although cardiovascular lability showed some association with both reactivity and resting blood pressure level, the resting blood pressure level-reactivity relationship survived statistical adjustment for such associations. Accordingly, the excessive cardiovascular reactions characteristic of individuals with elevated resting blood pressure would not appear to be explainable, to any substantial extent, by lability effects.

Adult↗
PubMed1997

Paracetamol with and without codeine in acute pain: a quantitative systematic review.

In order to assess the analgesia obtained from single oral doses of paracetamol alone and in combination with codeine in postoperative pain, we conducted a systematic review of randomised controlled trials. We found 31 trials of paracetamol against placebo with 2515 patients, 19 trials of paracetamol plus codeine against placebo with 1204 patients and 13 trials of paracetamol plus codeine against the same dose of paracetamol with 874 patients. Pain relief information was extracted, and converted into dichotomous information (number of patients with at least 50% pain relief). Wide variations in responses to placebo (0-72%) and active drug (3-89%) were observed. In postoperative pain states paracetamol 1000 mg alone against placebo had an number-needed-to-treat (NNT) of 3.6 (3.0-4.4) and paracetamol 600/650 mg alone an NNT of 5.0 (4.1-6.9). Paracetamol 600/650 mg plus codeine 60 mg against placebo had a better NNT of 3.1 (2.6-3.8), with no overlap of 95% confidence intervals with paracetamol 600/650 mg alone. In direct comparisons of paracetamol plus codeine with paracetamol alone the additional analgesic effect of 60 mg of codeine added to paracetamol was 12 extra patients in every 100 achieving at least 50% pain relief. In indirect comparisons of each with placebo it was 14 extra patients per 100. This was an NNT for adding codeine 60 mg of 9.1 (5.8-24). The results confirm that paracetamol is an effective analgesic, and that codeine 60 mg added to paracetamol produces worthwhile additional pain relief even in single oral doses.

Acetaminophen↗
PubMed1997

Pain relief from intra-articular morphine after knee surgery: a qualitative systematic review.

Reduction of postoperative pain by injecting opioid into the knee joint is believed to support the hypothesis of peripheral opioid receptor activation in inflammation. The study design consisted of a systematic review of randomised controlled trials (RCTs). Main outcomes were pain intensity and the use of supplementary analgesics. Efficacy of intra-articular bupivacaine against placebo was used as an index of internal sensitivity. Evidence of efficacy was sought in both early (0-6 h after intra-articular injection) and late (6-24 h) periods. Thirty-six RCTs in knee surgery were found. Six had both a local anaesthetic control and placebo; four showed internal sensitivity. All four sensitive studies had at least one outcome showing efficacy of intra-articular morphine against placebo. Six studies compared intra-articular morphine with intravenous or intramuscular morphine or with intra-articular saline without a bupivacaine control. Four of the six studies showed greater efficacy for intra-articular morphine. There was no dose-response evident. No quantitative analysis of pooled data was done. We conclude that intra-articular morphine may have some effect in reducing postoperative pain intensity and consumption of analgesics. These studies had significant problems in design, data collection, statistical analysis and reporting. Trials of better methodological quality are needed for a conclusive answer that intra-articular morphine is analgesic, and that any analgesia produced is clinically useful.

Analgesics, Opioid↗
PubMed1997

The relationship between socioeconomic status, hostility, and blood pressure reactions to mental stress in men: data from the Whitehall II study.

This study investigated the relationship among blood pressure reactions to mental stress, cynical hostility, and socioeconomic status (SES) in 1,091 male public servants. Occupational grade served to index SES and cynical hostility was assessed using the Cook-Medley scale. (Cook & Medley, 1954). The magnitude of systolic, but not diastolic, blood pressure change scores to stress was positively associated with occupational grade: the higher the grade, the greater the reactions. Mental stress task performance also varied with occupational grade but was unrelated to reactivity. Ratings of task difficulty did not vary with occupational grade. Cynical hostility was negatively related to occupational grade, and, contrary to previous findings, negatively related to systolic blood pressure reactivity. Cynical hostility was also negatively related to mental stress task performance but unrelated to ratings of task difficulty.

Adult↗
PubMed1997

The effects of recent food, alcohol, and tobacco intake and the temporal scheduling of testing on cardiovascular activity at rest and during psychological stress.

Participants in cardiovascular psychophysiological studies receive various instructions regarding restraints on alcohol, food, and tobacco intake prior to testing. Further, although the hour of testing is frequently a concern, little attention is paid to month of the year. In the present study, we examined cardiovascular activity at rest and in response to a laboratory stress task in 1,272 men in terms of these variables. Alcohol consumption among alcohol users and food intake within 4 hr of testing were associated with higher baseline diastolic blood pressure (BP) but lower baseline heart rate (HR). Tobacco use in smokers within 1 hr of testing was associated with elevated baseline BP and HR. Hour of testing was related to baseline HR, whereas month of the year was associated with baseline BP. In contrast to these baseline effects, cardiovascular reactions to the laboratory stress task were largely immune to these contextual influences.

Adult↗
PubMed1997

Transcutaneous electrical nerve stimulation in labour pain: a systematic review.

OBJECTIVE: To review the effectiveness and safety of transcutaneous electrical nerve stimulation (TENS) for labour pain. DESIGN: A systematic review of randomised controlled trials of TENS in pain during labour. SAMPLE: Eight reports involving 712 women were included; 352 women received active TENS and 360 acted as controls. METHODS: Reports were sought by searching MEDLINE and the Oxford Pain Relief Database. MAIN OUTCOME MEASURES: Analgesic and adverse effect outcomes. RESULTS: Evidence for reduced pain using TENS in labour was weak. Additional analgesic interventions may be less likely with TENS (odds ratio 0.57; 95% CI 0.34-0.96), number-needed-to-treat 14 (95% CI 7.3-119). CONCLUSIONS: Randomised controlled trials provide no compelling evidence for TENS having any analgesic effect during labour. Weak positive effects in secondary (analgesic sparing) and tertiary (choosing TENS for future labours) outcomes may be due to inadequate blinding causing overestimation of treatment effects.

Female↗
PubMed1997

Processing of targeted psoralen cross-links in Xenopus oocytes.

Psoralen cross-links have been shown to be both mutagenic and recombinagenic in bacterial, yeast, and mammalian cells. Double-strand breaks (DSBs) have been implicated as intermediates in the removal of psoralen cross-links. Recent work has suggested that site-specific mutagenesis and recombination might be achieved through the use of targeted psoralen adducts. The fate of plasmids containing psoralen adducts was evaluated in Xenopus oocytes, an experimental system that has well-characterized recombination capabilities and advantages in the analysis of intermediates in DNA metabolism. Psoralen adducts were delivered to a specific site by a triplex-forming oligonucleotide. These lesions are clearly recognized and processed in oocytes, since mutagenesis was observed at the target site. The spectrum of induced mutations was compared with that found in similar studies in mammalian cells. Plasmids carrying multiple random adducts were preferentially degraded, perhaps due to the introduction of DSBs. However, when DNAs carrying site-specific adducts were examined, no plasmid loss was observed and removal of cross-links was found to be very slow. Sensitive assays for DSB-dependent homologous recombination were performed with substrates with one or two cross-link sites. No adduct-stimulated recombination was observed with a single lesion, and only very low levels were observed with paired lesions, even when a large proportion of the cross-links was removed by the oocytes. We conclude that DSBs or other recombinagenic structures are not efficiently formed at psoralen adducts in Xenopus oocytes. While psoralen is not a promising reagent for stimulating site-specific recombination, it is effective in inducing targeted mutations.

Animals↗
PubMed1997

Altered expression of p53 and mdm-2 proteins at diagnosis is associated with early treatment failure in childhood acute lymphoblastic leukemia.

PURPOSE: To determine whether potential alteration in p53 function through p53 gene mutation or mdm-2 overexpression correlates with early treatment failure in childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Diagnostic marrow samples from 34 children were analyzed for p53 gene alterations by western blot and SSCP/DNA sequence analysis and for mdm-2 overexpression by western blot analysis. These samples were derived from two groups of children with ALL: 17 good outcome patients who are in long-term continuous complete remission and 17 poor outcome patients who did not achieve a complete remission or relapsed within 6 months of achieving remission. RESULTS: Two children within the poor outcome group were found to have p53 gene mutations. Furthermore, five poor outcome patients were shown to have greater than 10-fold overexpression of mdm-2 protein compared with the mean level of mdm-2 protein measured in the good outcome group. Aberrant p53 protein expression was found in only one good outcome patient, whereas no good outcome children were found to have elevated levels (> 10-fold) of mdm-2 protein. CONCLUSION: We show for the first time that potential alteration in p53 function in childhood ALL is more common (P = .036) in cases of early treatment failure than in children who remain in long-term continuous remission.

Child↗
PubMed1996

Effects of protein calorie malnutrition on tuberculosis in mice.

Infectious diseases and malnutrition represent major burdens afflicting millions of people in developing countries. Both conditions affect individuals in industrialized nations, particularly the aged, the HIV-infected, and people with chronic diseases. While malnutrition is known to induce a state of immunodeficiency, the mechanisms responsible for compromised antimicrobial resistance in malnourished hosts remain obscure. In the present study, mice fed a 2% protein diet and developing protein calorie malnutrition, in contrast to well-nourished controls receiving a 20% protein diet, rapidly succumbed to infection with Mycobacterium tuberculosis. Malnourished mice exhibited a tissue-specific diminution in the expression of interferon gamma, tumor necrosis factor alpha, and the inducible form of nitric oxide synthase in the lungs, but not the liver. The expression of these molecules critical to the production of mycobactericidal nitrogen oxides was depressed in malnourished animals in the lungs specifically at early times (< 14 days) after infection. At later times, levels of expression became comparable to those in well-nourished controls, although the bacillary burden in the malnourished animals continued to rise. Nevertheless, urinary and serum nitrate contents, an index of total nitric oxide (NO) production in vivo, were not detectably diminished in malnourished, mycobacteria-infected mice. In contrast to the selective and early reduction of lymphokines and the inducible form of nitric oxide synthase in the lung, a marked diminution of the granulomatous reaction was observed in malnourished mice throughout the entire course of infection in all tissues examined (lungs, liver, and spleen). Remarkably, the progressively fatal course of tuberculosis observed in the malnourished mice could be reversed by restoring a full protein (20%) diet. The results indicate that protein calorie malnutrition selectively compromises several components of the cellular immune response that are important for containing and restricting tuberculous infection, and suggest that malnutrition-induced susceptibility to some infectious diseases can be reversed or ameliorated by nutritional intervention.

Animals↗
PubMed1996

Spinal cord NMDA receptors modulate peripheral immune responses and spinal cord c-fos expression after immune challenge in rats subjected to unilateral mononeuropathy.

To characterize further the neural involvement in local immune reactions, we evaluated the effect of intrathecal NMDA-receptor blocker dizocilpine maleate (MK-801) on the peripheral immune response itself and on spinal cord c-fos expression induced by the delayed-type hypersensitivity (DTH) response. Immune challenge took place in the hind paw ipsilateral or contralateral to an injured sciatic nerve in both previously sensitized and immune-naive animals. An enhanced immune response was observed bilaterally in the hind paws of animals subjected to unilateral mononeuropathy compared with sham-operated controls. In contrast, no such enhancement was observed when neuropathic animals were challenged in the front paws. The increased DTH response was blocked successfully by the intrathecal administration of an analgesic dose of MK-801. Compared with sham-operated animals, animals subjected to unilateral mononeuropathy showed both a differential distribution and an increase in the number of c-fos-labeled neurons in the dorsal horn of the L3-L5 spinal cord segments after immune challenge. This was observed irrespective of whether the challenge took place ipsilateral or contralateral to the injured nerve. In addition to reversing the changes in immune response, intrathecal administration of MK-801 reversed the pattern of c-fos immunoreactivity in the spinal cord after immune challenge in neuropathic animals. These data suggest that select groups of spinal cord neurons participate in enhancing the peripheral immune response to a specific antigen in neuropathic animals and that this enhancement involves central NMDA receptors.

Animals↗
PubMed1996

Assessing the quality of reports of randomized clinical trials: is blinding necessary?

It has been suggested that the quality of clinical trials should be assessed by blinded raters to limit the risk of introducing bias into meta-analyses and systematic reviews, and into the peer-review process. There is very little evidence in the literature to substantiate this. This study describes the development of an instrument to assess the quality of reports of randomized clinical trials (RCTs) in pain research and its use to determine the effect of rater blinding on the assessments of quality. A multidisciplinary panel of six judges produced an initial version of the instrument. Fourteen raters from three different backgrounds assessed the quality of 36 research reports in pain research, selected from three different samples. Seven were allocated randomly to perform the assessments under blind conditions. The final version of the instrument included three items. These items were scored consistently by all the raters regardless of background and could discriminate between reports from the different samples. Blind assessments produced significantly lower and more consistent scores than open assessments. The implications of this finding for systematic reviews, meta-analytic research and the peer-review process are discussed.

Double-Blind Method↗
PubMed1996

Developing a database of published reports of randomised clinical trials in pain research.

A database of randomised clinical trials (RCTs) in pain research published from 1950 to 1990 was created following an extensive literature search. By applying a refined MEDLINE search strategy from 1966 to 1990 and by hand-searching more than 1,000,000 pages of a total of 40 biomedical journals published during the period 1950-1990, more than 8000 RCTs were identified. The RCTs were published in more than 800 journals and over 85% appeared between 1976 and 1990. If the trend of the last 15 years persists, a total of more than 15 000 RCTs will be published in pain relief by the year 2000. A detailed description of methods to ensure efficient use of resources during the identification, retrieval and management of the information in pain relief and other fields is given. Emphasis is made on the importance of refining MEDLINE search strategies, on the use of volunteers to hand-search journals and on careful monitoring of each of the steps of the process. The potential uses of the database to guide clinical and research decisions are discussed.

Databases, Bibliographic↗
PubMed1996

Ibuprofen compared with ibuprofen plus caffeine after third molar surgery.

OBJECTIVES: To compare the relative merits of single doses of ibuprofen and ibuprofen plus caffeine in the treatment of pain after third molar removal. DESIGN: Randomised, double-blind, placebo-controlled, single-dose parallel-group comparison of placebo, ibuprofen 200 and 400 mg with ibuprofen 200 mg plus 50, 100 or 200 mg of caffeine. SUBJECTS: 161 patients undergoing lower third molar removal. RESULTS: All active treatments produced significant analgesia and mood elevation compared with placebo. There was no significant difference in the effects of 200 and 400 mg of ibuprofen. Adding caffeine to 200 mg ibuprofen produced significantly more analgesic effect at 45 and 60 min than ibuprofen 200 mg alone. Ten patients reported 11 adverse effects, none in the highest caffeine dose group. CONCLUSIONS: Caffeine increased the analgesic effect of ibuprofen 200 mg, through an earlier onset of analgesic effect. This was achieved in this single dose context without problematic adverse effects.

Adult↗
PubMed1996

Homologous genetic recombination in Xenopus: mechanism and implications for gene manipulation.

Appropriately designed DNA substrates undergo very efficient homologous recombination after injection into the nuclei of Xenopus laevis oocytes. The requirements for this process are that the substrate be linear, that it have direct repeats to support recombination, and that these repeats be at or very near the molecular ends. Taking advantage of direct nuclear injection, the large amounts of DNA processed in a single oocyte, and the accessibility of recombination intermediates, we were able to analyze the mechanism of recombination in detail. Molecular ends are resected by a 5'-->3' exonuclease activity. When complementary sequences are exposed from two ends, they anneal. Continued 5'-->3' degradation removes the redundant strands; the 3' ends pair with their complements and can be extended by DNA polymerase to fill any gap left by the exonuclease. Joining of strands by DNA ligase completes the process. This mechanism is nonconservative, in that only one of the two original repeats is retained, and it has been dubbed single-strand annealing, or SSA. The capability for SSA accumulates during the later phases of oogenesis and persists into the egg. This pattern suggests that, like many activities of full-grown oocytes, SSA is stored for use during embryogenesis. The same or a very similar mechanism is prevalent in many other species, including bacteria, yeast, plants, and mammals, where it often provides the predominant mode of recombination of extrachromosomal DNA. Lessons learned about SSA are applicable to methods of gene manipulation. It is plausible that SSA has a normal function in the repair of double-strand breaks, but proof of this awaits identification of genes and enzymes uniquely involved in this style of recombination.

Animals↗
PubMed1996

Collaborative care between nurse practitioners and primary care physicians.

Primary care practices are looking at methods of providing quality care for an increasing number of patients, and one method of achieving this goal is the development of a collaborative agreement with a physician(s) and nurse practitioner(s). There is a need for information about the role of the nurse practitioner and the advantages of collaboration. This article reviews the history of the nurse practitioner movement, practice standards, and the scope of practice for nurse practitioners. Models of collaborative practice and the advantages of these models are discussed. Considerations for entering into collaborative practice are addressed also.

Humans↗