Search PubMed⌕ Search

Biomedical subjects

C Richardson

Publications and source records attributed to C Richardson.

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

Dexmedetomidine does not alter the sweating threshold, but comparably and linearly decreases the vasoconstriction and shivering thresholds.

BACKGROUND: Clonidine decreases the vasoconstriction and shivering thresholds. It thus seems likely that the alpha2 agonist dexmedetomidine will also impair control of body temperature. Accordingly, the authors evaluated the dose-dependent effects of dexmedetomidine on the sweating, vasoconstriction, and shivering thresholds. They also measured the effects of dexmedetomidine on heart rate, blood pressures, and plasma catecholamine concentrations. METHODS: Nine male volunteers participated in this randomized, double-blind, cross-over protocol. The study drug was administered by computer-controlled infusion, targeting plasma dexmedetomidine concentrations of 0.0, 0.3, and 0.6 ng/ml. Each day, skin and core temperatures were increased to provoke sweating and then subsequently reduced to elicit vasoconstriction and shivering. Core-temperature thresholds were computed using established linear cutaneous contributions to control of sweating, vasoconstriction, and shivering. The dose-dependent effects of dexmedetomidine on thermoregulatory response thresholds were then determined using linear regression. Heart rate, arterial blood pressures, and plasma catecholamine concentrations were determined at baseline and at each threshold. RESULTS: Neither dexmedetomidine concentration increased the sweating threshold from control values. In contrast, dexmedetomidine administration reduced the vasoconstriction threshold by 1.61 +/- 0.80 degrees C x ng(-1) x ml (mean +/- SD) and the shivering threshold by 2.40 +/- 0.90 degrees C x ng(-1) x ml. Hemodynamic responses and catecholamine concentrations were reduced from baseline values, but they did not differ at the two tested dexmedetomidine doses. CONCLUSIONS: Dexmedetomidine markedly increased the range of temperatures not triggering thermoregulatory defenses. The drug is thus likely to promote hypothermia in a typical hospital environment; it is also likely to prove an effective treatment for shivering.

Adrenergic alpha-Agonists↗
PubMed1997

Dynamic imaging of functional nerve terminals and Schwann cells in presynaptic 'nerve plates' isolated from the skate electric organ

The cholinergic innervation and its glial support were isolated in a functional state from the electric organ of the skate (Raja species) using a combined enzymatic and mechanical dissociation technique. Examination using light and electron microscopy showed that this 'nerve plate' is a disc-shaped structure several hundred micrometres in diameter consisting of a dense plexus of nerve terminals attached to branching nerve fibrils with numerous associated myelinating and perisynaptic Schwann cells. In unfixed nerve plates, depolarisation and Ca2+-dependent staining of the nerve terminals was seen with RH-414, a fluorescent marker for functional motor terminals. The components of the nerve plate could be loaded with the Ca2+-sensitive dyes Fluo-3 and Fura-2. Depolarisation of nerve plates loaded with either dye leads to an immediate increase of intracellular Ca2+ levels ([Ca2+]i) in the nerve terminals. This response was blocked by certain Ca2+ channel antagonists from the -conotoxin family. Glial cell responses to depolarisation were in general minimal. However, increases of [Ca2+]i were seen in these cells, but not in nerve terminals, during applications of ATP and acetylcholine. These results show that both nerve terminal and glial elements in this 'nerve plate' preparation are functional. The ease of this preparation and its functional reliability give it considerable potential as a useful model for elucidating presynaptic mechanisms.

Journal Article↗
PubMed1996

Refining the treatment of women with unstable angina--a randomized, double-blind, comparative safety and efficacy evaluation of Integrelin versus aspirin in the management of unstable angina.

BACKGROUND: Although women typically develop coronary artery disease several years after men, once they have symptomatic disease their thromboembolic complications are worse than in men. The mechanism mediating this gender difference in outcome after thromboembolic events is unknown. We previously studied platelet functions in siblings from patients with premature coronary artery disease. We observed that platelets from women are responsive than their male counterparts. In particular, platelets from women stimulated ex vivo with various agonists bind more fibrinogen molecules than platelets from men. HYPOTHESIS: We hypothesized that in patients with acute coronary events, the control of platelet activity might require stronger antagonists in women than in men. METHODS: To test this hypothesis, we investigated retrospectively the results of a trial on Integrelin in unstable angina. RESULTS: We report that platelet aggregation and Holter-detected ischemic episodes are significantly reduced in women with unstable angina treated with the specific GPIIb-IIIa inhibitor, Integrelin, compared with the standard platelet inhibitor aspirin. In contrast, both platelet aggregation and Holter-detected ischemic events are well controlled in men with unstable angina treated with standard therapy including aspirin. CONCLUSION: Integrelin does provide protection in men, but, in contrast with women, not beyond what can be achieved with aspirin. Our data are consistent with the concept that the platelets from women require stronger and more specific inhibitors to limit their activity, and that platelets may play a more important role in women with acute coronary syndromes than in men. Most important, specific GPIIb-IIIa inhibitors may represent a therapeutic option which provides as much suppression of ischemic events in women as they do in men with coronary artery disease.

Aged↗
PubMed1996

Evaluation of the relationship between laboratory and clinical tests of transversus abdominis function.

A clinical test of the function of the deep abdominal muscles was compared to a laboratory electromyographic (EMG) investigation of the contribution of transversus abdominis (TrA) to stability of the lumbar spine during limb movement. The two different functions of TrA were evaluated in 15 subjects. The subject group included six subjects with chronic low back pain and nine subjects with no history of low back pain so that the resultant recordings were spread over a wide range for each test. The clinical test involved quantification of the ability of the subjects to specifically displace the anterior abdominal wall in a way consistent with the function of the muscle. This was evaluated by use of a device designed to measure pressure reduction as the abdomen lifted off a transducer in the prone position. The laboratory test involved determination of the onset of contraction of TrA associated with rapid upper limb movement, measured using fine-wire EMG electrodes. The parameter evaluated was the latency between the contraction of TrA and the prime mover of the limb. Data were analysed both as absolute values and as ordinal data of a three-rating scale derived from criteria based on current knowledge of the response to both tests. No significant correlation was found between the absolute magnitudes of the pressure and timing data, however, comparison of the rating scale data indicated a significant relationship between the tests and associated high level of agreement between the two measures. The results of the study indicate that a reduction in the ability to draw in the abdominal wall is related to changes in the coordination of TrA, although the magnitude of the changes were not correlated. The degree of causality between these co-varying but independent manifestations of the function of TrA is uncertain.

Abdominal Muscles↗
PubMed1996

Psychosocial problems and adjustment of children with beta-thalassemia and their families.

This study explores the psychosocial problems experienced by families with children aged 6 to 14 years suffering from beta-thalassemia major (N = 188). The psychosocial problems and the family's adjustment to the effects of the illness were compared across a number of cultures where the disease is prevalent, namely Cyprus, Greece, and Italy. A small number of migrant children in the United Kingdom was also included in the study. Semi-structured interviews were conducted with parents who also completed the Rutter Parental Questionnaire and the Goldberg General Health Questionnaire. Teachers were asked to complete a Children's Behaviour Questionnaire designed by Rutter. In all countries the disease seemed to have a binding effect on the family, thus mobilizing adaptive mechanisms. Father's low education level and the presence of major medical complications were predictors of poor family adjustment. Differences between and within countries may well reflect differences in health policies, existing level of socio-economic development, and in the cultural patterns in coping with a chronic illness.

Adaptation, Psychological↗
PubMed1996

Developmental-stage-specific expression and regulation of an amphotropic retroviral receptor in hematopoietic cells.

Expression of the transmembrane receptor protein Ram-1 may be critical to optimizing retroviral gene transfer. Ram-1 acts as both a sodium-dependent phosphate transporter and a receptor for amphotropic retroviruses. We previously reported detectable Ram-1 in murine hematopoietic fetal liver cells (FLC) despite resistance of these cells to amphotropic retroviral transduction (infection). We document here that Ram-1 expression is completely absent in murine yolk sac cells from days 9.5 through 13.5 of ontogeny and first appears at low levels in midgestational FLC between days 13.5 and 14.5. In addition, Ram-1 expression is detected only in more differentiated populations within FLC, day 14.5, and not in those highly enriched for stem cells, indicating developmental regulation of Ram-1 during murine hematopoiesis. Others have reported the in vitro use of phosphate-free medium as a stimulus to increase levels of Ram-1 mRNA in nonhematopoietic cells. We now demonstrate that Ram-1 poly(A)+ mRNA increases significantly following culture of FLC in phosphate-free medium. Further, transduction of FLC in phosphate-free medium with an amphotropic retrovirus containing the multiple drug resistance gene leads to gene transfer not observed previously. These data demonstrate that (i) the normal resistance of FLC to amphotropic transduction is most likely due to an insufficient number of Ram-1 molecules for efficient retroviral recognition and binding, and (ii) Ram-1 can be upregulated by increasing the need for phosphate transport across the cell membrane.

Animals↗
PubMed1996

Factors modifying protective effect of anti-CD18 antibodies on myocardial reperfusion injury in dogs.

Anti-CD18 monoclonal antibodies (MAb) have demonstrated variable protection against neutrophil (PMN)-mediated myocardial reperfusion injury. To identify factors contributing to this variability, open-chest dogs underwent coronary artery occlusion for 90 min followed by reperfusion for 3.5 h. Ten minutes before reperfusion the dogs received saline (n = 18) or one of three anti-CD18 MAb: MHM.23, R15.7, or PLM-2 (2, 1, and 1 mg/kg and n = 19, 8, and 4, respectively). Collateral flow was measured with radioactive microspheres, area at risk was assessed with monastral blue dye, and infarct size was measured postmortem by triphenyltetrazolium chloride. In vitro, all three MAb bound to canine PMNs, but only MHM.23 and R15.7 inhibited their adherence to keyhole limpet hemocyanin-coated plastic. In vivo, only MHM.23 and R15.7 significantly reduced infarct size after adjusting for the effect of collateral flow. MHM.23 afforded protection in dogs with moderate ischemia (epicardial collateral flow > 0.1 ml.min-1.g-1, infarct size reduced 46%) but not in dogs with more severe ischemia. Only R15.7 was effective in dogs with severe ischemia. Although MHM.23 and R15.7 produced similar inhibition of tissue PMN accumulation, as reflected by myeloperoxidase activity. R15.7 markedly inhibited H2O2 production by PMNs after exposure to platelet-activating factor, whereas MHM.23 had only a minimal effect. The effectiveness of different anti-CD18 MAb in preventing reperfusion injury appears to be 1) highly dependent on the specific anti-CD18 MAb employed, 2) predicted only partially by in vitro binding to PMNs, static in vitro tests of PMN adherence, or the extent of inhibition of PMN accumulation in vivo, 3) related more to their ability to inhibit oxidant release from activated PMNs, and 4) strongly influenced by the severity of myocardial ischemia before reperfusion.

Animals↗
PubMed1996

The clinical implications of inhibition of the inducible form of cyclo-oxygenase.

There are 2 isoenzymes of cyclo-oxygenase (COX). There is a constitutive enzyme COX-1 which has a wide tissue distribution. In addition there is an inducible enzyme COX-2 which has a restricted tissue distribution. The inducible enzyme COX-2 is responsible for the generation of prostaglandins at sites of tissue inflammation and its inhibition is associated with an anti-inflammatory action. The constitutive enzyme, COX-1 is responsible for the production of prostaglandins with multiple functions. One well known and clinically important function is the gastroprotective effect of the prostaglandins produced in the gastric mucosa. While selective COX-2 inhibition may be associated with a reduced incidence of gastric adverse effects, a concern remains that its inhibition at other locations may be associated with other adverse effects.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1996

Laboratory markers of disease activity.

Rheumatoid arthritis is associated with numerous abnormalities measurable in a laboratory. These are most commonly used to monitor disease but can also provide prognostic information; less frequently they are used to support a clinical diagnosis. In general, quantitative markers are used for monitoring early disease. By contrast, qualitative markers can provide prognostic information of particular relevance to early therapy. The markers with the best features for predication of radiological erosions are the MHC conserved epitope and rheumatoid factor. In established disease most of the quantitative measures indicate poor prognosis. Therefore, the choice of the best marker depends not only on the purpose for which it is desired, but also on the stage of disease.

Acute-Phase Reaction↗
PubMed1996

Retroviral transfer and expression of the human multiple drug resistance (MDR) gene in peripheral blood progenitor cells.

The multiple drug resistance (MDR) gene P-glycoprotein product is a transmembrane efflux pump that prevents toxicity of a variety of chemotherapeutic agents, including the anthracyclines, Vinca alkaloids, podophyllins, and taxol. The bone marrow toxicity of these drugs is due to the low or absent expression of MDR in marrow cells. Transfer and expression of the human MDR gene into bone marrow progenitors should prevent this toxicity. We report here the efficient transfer and expression of the MDR gene by retroviral-mediated gene transfer into CD34(+) cells isolated from peripheral blood progenitor cells (PBPCs), comparable to that obtained using bone marrow-derived progenitors. Optimal MDR transduction of these PBPC-derived cells requires exposure to growth factors and a period of preincubation. In addition, we demonstrate that we can transduce up to 100% of progenitor cells derived from PBPCs and can protect up to 25% of these progenitors from a dose of taxol toxic to untransduced controls.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Preselection of transduced murine hematopoietic stem cell populations leads to increased long-term stability and expression of the human multiple drug resistance gene.

We have been using the human multiple drug resistance (MDR) gene to transduce murine hematopoietic cells via retroviruses as a model system for potential human gene therapy. In this paper, we show that transplantation of MDR-transduced midgestational fetal liver cells (FLCs) into lethally irradiated mice leads to the continued presence and expression of the human MDR gene in the short-lived granulocyte-macrophages of recipients' peripheral blood (PB) for up to 12 months. We have also shown the ability of this retroviral system to efficiently transduce several murine FLC subpopulations enriched for hematopoietic stem cells (FL-HSCs) both (1) short-term by MDR-polymerase chain reaction analysis of individual day 12 colony-forming unit-spleen and (2) long-term by in vivo maintenance of MDR and expression of its product, p-glycoprotein, up to 1 year in PB. More highly enriched FL-HSC subpopulations show the greatest number of circulating granulocyte-macrophage cells expressing MDR long-term. These studies also show that preselection by fluorescence-activated cell sorting of MDR-transduced and -expressing cells before transplant significantly increases the percentage of circulating granulocyte-macrophage cells that express MDR at all time points analyzed posttransplant as compared with unsorted cells transduced in the same manner (P < .01). These results have potentially significant implications for future human gene therapy trials.

3T3 Cells↗
PubMed1995

A redrawn Vandenberg and Kuse mental rotations test: different versions and factors that affect performance.

The available versions of the Vandenberg and Kuse (1978) Mental Rotations Test (MRT) have physically deteriorated because only copies of copies are available. We report results from a redrawn version of the MRT and for alternate versions of the test. Males perform better than females, and students drawn from the physical sciences perform better than students drawn from the social sciences and humanities, confirming other reports with the original version of the MRT. Subjects find it very hard to perform the MRT when stimuli require rotation along both the top/bottom axis and the left/right axis. The magnitude of effect sizes for sex (which account, on average, for some 20% of the variance) does not increase with increasing difficulty of the task. Minimal strategy effects were observed and females did not perform differently during the menstrual period as opposed to the days between the menstrual periods. Practice effects are dramatic, confirming other reports with the original MRT, and can also be shown to be powerful in a transfer for practice paradigm, where test and retest involve different versions of the MRT. Main effects of handedness on MRT performance were not found.

Adult↗
PubMed1995

A time series analysis of the relationship between ambulatory EMG, pain, and stress in chronic low back pain.

Twenty-one subjects with chronic back pain (CBP) participated in an ambulatory electromyography (EMG) monitoring study to ascertain the relationships between muscle activity, physical activity, psychosocial stress, and pain. A time-series analysis approach was adopted to investigate both immediate and lagged associations between these variables in an attempt to determine potential causal relationships. Results for group relationships showed a significant relationship between physical activity and pain, self-report of stress and pain, but no relationship between EMG activity and pain. A lagged relationship between physical activity and pain was found, suggesting a causal relationship between physical activity and pain. However, no time lag was observed between stress and pain, hence no causal relationship can be elucidated. Analysis at the individual level indicated stronger relationships between several combinations of these variables, highlighting the need to consider the heterogeneity of the CBP population and etiology of CBP. The use of ambulatory monitoring of pain, stress, and EMG is suggested as one avenue to further explore the population's heterogeneity.

Adult↗
PubMed1995

The Ypt1 GTPase is essential for the first two steps of the yeast secretory pathway.

Small GTPases of the rab family are involved in the regulation of vesicular transport. The restricted distribution of each of these proteins in mammalian cells has led to the suggestion that different rab proteins act at different steps of transport (Pryer, N. K., L. J. Wuestehube, and R. Sheckman. 1992. Annu Rev. Biochem. 61:471-516; Zerial, M., and H. Stenmark. 1993. Curr. Opin. Cell Biol. 5:613-620). However, in this report we show that the Ypt1-GTPase, a member of the rab family, is essential for more than one step of the yeast secretory pathway. We determined the secretory defect conferred by a novel ypt1 mutation by comparing the processing of several transported glycoproteins in wild-type and mutant cells. The ypt1-A136D mutant has a change in an amino acid that is conserved among rab GTPases. This mutation leads to a rapid and tight secretory block upon a shift to the restrictive temperature, and allows for the identification of the specific steps in the secretory pathway that directly require Ypt1 protein (Ypt1p). The ypt1-A136D mutant exhibits tight blocks in two secretory steps, ER to cis-Golgi and cis- to medial-Golgi, but later steps are unaffected. Thus, it is unlikely that Ypt1p functions as the sole determinant of fusion specificity. Our results are more consistent with a role for Ypt1/rab proteins in determining the directionality or fidelity of protein sorting.

Base Sequence↗