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Biomedical subjects

M A Peterson

Publications and source records attributed to M A Peterson.

At least 19 recordsLinked to original sources
PubMed2000

Glucose-derived 3'-(carboxymethyl)-3'-deoxyribonucleosides and 2', 3'-lactones as synthetic precursors for amide-linked oligonucleotide analogues.

Treatment of a 1,2-O-isopropylidene-3-ketopentofuranose derivative (obtained from D-glucose) with [(ethoxycarbonyl)methylene]triphenylphosphorane and catalytic hydrogenation of the resulting alkene gave stereodefined access to 3-(carboxymethyl)-3-deoxy-D-ribofuranose derivatives. Esters of 5-O-acetyl- or 5-azido-5-deoxy-3-(carboxymethyl)-D-ribofuranose were coupled with nucleobases to give branched-chain nucleoside derivatives. Ester saponification and protecting group manipulation provided 2'-O-(tert-butyldimethylsilyl) ethers of 5'-azido-5'-deoxy- or 5'-O-(dimethoxytrityl) derivatives of 3'-(carboxymethyl)-3'-deoxyribonucleosides that are effective precursors for synthesis of amide-linked oligoribonucleosides.

Deoxyadenosines↗
PubMed2000

Object memory effects on figure assignment: conscious object recognition is not necessary or sufficient.

In three experiments we investigated whether conscious object recognition is necessary or sufficient for effects of object memories on figure assignment. In experiment 1, we examined a brain-damaged participant, AD, whose conscious object recognition is severely impaired. AD's responses about figure assignment do reveal effects from memories of object structure, indicating that conscious object recognition is not necessary for these effects, and identifying the figure-ground test employed here as a new implicit test of access to memories of object structure. In experiments 2 and 3, we tested a second brain-damaged participant, WG, for whom conscious object recognition was relatively spared. Nevertheless, effects from memories of object structure on figure assignment were not evident in WG's responses about figure assignment in experiment 2, indicating that conscious object recognition is not sufficient for effects of object memories on figure assignment. WG's performance sheds light on AD's performance, and has implications for the theoretical understanding of object memory effects on figure assignment.

Aged↗
PubMed2000

Opioid inhibition of formalin-induced changes in plasma extravasation and local blood flow in rats.

Hindpaw injection of dilute formalin produces brief (Phase 1) and persistent (Phase 2) nociceptive responses in the rat. We recently showed that systemically-administered remifentanil during Phase 1 interacted with peripheral opioid receptors to delay the onset and termination of Phase 2 (Taylor et al., 1997b). To test the hypothesis that opioid inhibition of proinflammatory events during Phase 1 contributed to this delay, we evaluated the effects of remifentanil on the time course of formalin-induced inflammation. We found that formalin increased paw thickness (edema), plasma extravasation and local blood flow within minutes of its injection, i.e. during Phase 1. Each of these responses was blocked during remifentanil administration (30 microg/kg i.v. bolus, followed 90 s later with a 15 microg/kg/min infusion for 13.5 min), indicating that opioids inhibit Phase 1 inflammation. Opioid blockade of the blood flow response could be reversed with a peripherally-acting opioid antagonist, naloxone methiodide, indicating that remifentanil acted upon peripheral opioid receptors. Although the administration of remifentanil during Phase 1 did not reduce the magnitude of inflammatory responses during Phase 2, it did delay the onset and termination of edema during Phase 2. As this corresponds to the effects of remifentanil on nociceptive responses during Phase 2, we suggest that opioid analgesics act upon peripheral sites to inhibit inflammation during Phase 1, leading to a delay in the temporal profile of inflammatory (and likely nociceptive) responses during Phase 2.

Analgesics, Opioid↗
PubMed1999

Prospective, randomized trial of template-assisted versus undirected written recording of physician records in the emergency department.

STUDY OBJECTIVE: To determine whether use of the T-System (Emergency Services Consultants, Irving, TX) template-generated medical documentation system (1) decreases physician evaluation time in the emergency department, (2) increases gross billing under the 1997 Health Care Financing Administration guidelines by minimizing downcoding caused by inadequate documentation, and (3) increases physician satisfaction with the documentation process, compared with the undirected written narrative format. METHODS: A prospective, randomized, unblinded, controlled, convenience trial of documentation with the T-System of ED templates versus undirected written documentation was conducted in the ED of a county-owned, university-affiliated hospital. All patients seen between the hours of 7 AM and 10 PM during a 16-day period were included. The intervention was varying the method of documentation of the emergency physician. Adequacy of randomization to the 2 documentation groups was assessed by comparing ED triage classification, patient disposition, level of training of the evaluating physician, and whether ED consultation with other services occurred. Outcome measurements included emergency physician total evaluation and treatment time, professional bill, and satisfaction, as evaluated by a questionnaire completed after the study period. The 2 documentation groups were compared by an intention-to-treat analysis and by Student's t test and the median test as appropriate. RESULTS: A total of 1,228 patient encounters were included. Emergency physician total evaluation and treatment time with template-directed documentation was 4.6 minutes less than with undirected recording, a difference that was not significant (95% confidence interval [CI], -9.2 to 18.3). Gross billing was $29. 60 more per patient (95% CI, $22.20 to $37.00) with the T-System, as assessed by our hospital coders. This difference was caused by a mean.50 (95% CI,.39 to.60) higher level of evaluation and management coding. Physicians preferred the T-System (P <.0005). CONCLUSION: Use of template-assisted documentation in the ED was associated with higher gross billing and physician satisfaction but no significant decrease in emergency physician total evaluation time.

Attitude of Health Personnel↗
PubMed1998

Age-related hemispheric asymmetry in object discrimination.

Young and elderly observers judged whether two sequentially presented images in either the left or right visual field (LVF or RVF) were the same or different. The two objects depicted were always from the same entry-level category, but could differ only in viewpoint (a "same" trial--observers were instructed to ignore viewpoint changes) and/or in exemplar (a "different" trial). Young observers showed no difference in sensitivity across visual fields. Elderly observers were less sensitive overall than young observers, and were less sensitive to stimuli presented in the LVF-RH than in the RVF-LH. The results of this experiment support the hypothesis that one type of visual cognitive functioning declines with age faster in the right hemisphere than in the left hemisphere.

Adolescent↗
PubMed1998

Pituitary-adrenocortical responses to persistent noxious stimuli in the awake rat: endogenous corticosterone does not reduce nociception in the formalin test.

Although glucocorticoids inhibit inflammation and are used to treat painful inflammatory rheumatic diseases, the contribution, if any, of endogenous pituitary-adrenocortical activity to the control of pain remains unclear. We report that injection of dilute formalin into the hindpaw not only evokes inflammation and pain-related behavior, but it also increases ACTH and corticosterone to a greater extent than restraint and saline injection alone. This difference was particularly robust during the final periods of pain-related behavior in the formalin test, when the ACTH and corticosterone (B) levels in the restraint/saline control group had returned to normal. These results indicate that formalin-evoked increases in ACTH and B reflect nociceptive input, rather than the stress associated with handling. To test the hypothesis that the formalin-induced increase in corticosterone reduces pain and inflammation, we next evaluated the effect of adrenalectomy (to prevent activation of glucocorticoid receptors) or high-dose dexamethasone (to saturate glucocorticoid receptors) on nociceptive processing in the formalin test. Neither adrenalectomy nor dexamethasone changed behavioral or cardiovascular nociceptive responses. Furthermore, the increases in blood pressure and heart rate produced by formalin may not be mediated by adrenomedullary catecholamine release. In addition, we conclude that the nociceptive component of the formalin stimulus is sufficient to activate the pituitary-adrenocortical system in the awake rat, but that the resulting release of corticosterone does not feed back and reduce nociceptive processing.

Adrenal Cortex↗
PubMed1997

The differential contribution of capsaicin-sensitive afferents to behavioral and cardiovascular measures of brief and persistent nociception and to Fos expression in the formalin test.

Intraplantar injection of dilute formalin evokes brief (Phase 1) and persistent (Phase 2) increases in primary afferent activity, pain behavior, and cardiovascular responses, and induces spinal cord Fos-like immunoreactivity (Fos-LI). Although previous studies demonstrated that the destruction of small diameter primary afferents with neonatal capsaicin treatment decrease formalin-evoked nociception, these studies only evaluated behavioral responses, and did not distinguish between Phase 1 and 2. To address these questions, we simultaneously evaluated formalin-evoked pain behavior (flinching of the afflicted paw), cardiovascular responses (heart rate and mean arterial pressure), and lumbar spinal cord Fos expression in control rats and in rats treated with capsaicin (100 mg/kg) one day postpartum. We found that neonatal capsaicin-treated rats, compared to controls, exhibited similar cardiovascular responses and slightly less flinching behavior during Phase 1. During Phase 2, however, capsaicin-treated rats exhibited 59% less flinching and 45% smaller heart rate responses. Also, in capsaicin-treated rats, we counted 59% fewer Fos-labeled neurons in the spinal cord. These results indicate that capsaicin-sensitive afferents contribute to formalin-evoked behavioral and cardiovascular responses and to spinal cord neuronal responses. The differential effect of neonatal capsaicin on nociception during Phase 1 and Phase 2 suggests that sensitization mechanisms during Phase 1 do not contribute to the magnitude of nociceptive responses during Phase 2.

Afferent Pathways↗
PubMed1997

Continuous intravenous infusion of naloxone does not change behavioral, cardiovascular, or inflammatory responses to subcutaneous formalin in the rat.

The opioid antagonist, naloxone, produces equivocal effects on the magnitude of nociceptive responses in several animal models of persistent pain, including the formalin test. Hindpaw injection of dilute formalin produces not only inflammation but also phasic (Phase 1) and persistent (Phase 2) behavioral and cardiovascular nociceptive responses in the rat. To test the hypothesis that endogenous opioid systems contribute to the magnitude of responses to intraplantar formalin injection, we evaluated the effects of continuous naloxone administration (0.01-100 mg/kg per h, i.v.) on formalin-evoked hindpaw inflammation, on behavioral indices of pain, flinching and licking pain behavior, and on changes in mean arterial pressure and heart rate. We report that naloxone, at doses less than 100 mg/kg per h, did not change any formalin-evoked response. Although the 100 mg/kg per h dose significantly decreased these responses, it also produced muscle rigidity and profound bradycardia. We conclude that endogenous opioids do not significantly modulate the nociceptive processing induced by subcutaneous formalin.

Animals↗
PubMed1997

Differential contribution of the two phases of the formalin test to the pattern of c-fos expression in the rat spinal cord: studies with remifentanil and lidocaine.

Injection of formalin in the rat hindpaw produces two phases of nociceptive behavior. Although it is generally agreed that the first phase results from direct chemical activation of nociceptive primary afferent fibers, the factors that contribute to the second phase are not established. In the present study, we monitored the expression of the c-fos protein to evaluate whether the pattern of activity of dorsal horn neurons differs as a result of ongoing afferent activity during the two phases. To selectively block the first or second phase, we respectively used remifentanil, a potent and short acting opiate agonist, and QX-314, a quaternary derivative of lidocaine, which does not cross the blood brain barrier. We also evaluated the effect of eliminating nociceptive behavior in both phases using both remifentanil and lidocaine or a combination of local anesthetics, bupivicaine and quaternary lidocaine. In all groups, formalin (5%, 50 microliters) was injected subcutaneously into the plantar surface of the hindpaw. To assess the nociceptive behavior produced by formalin, we monitored the number of flinches. Injection of remifentanil during the first phase completely blocked the first phase formalin-evoked nociceptive behavior, and had no effect on the second phase. Injection of lidocaine during the interphase completely blocked second phase nociceptive behavior. As expected, when remifentanil was administered during the first phase and lidocaine during the second phase, all formalin-evoked nociceptive behavior was blocked. The same was true for rats that received injections of bupivicaine and lidocaine during phases 1 and 2, respectively. In laminae I-II of the L4-L5 segment, the magnitude of the decrease in Fos expression was comparable for remifentanil (26.5%) and lidocaine (27.3%); the decrease was greater when both remifentanil and lidocaine were administered (50.5%), and even greater when bupivicaine and lidocaine were used (74.2%). In laminae V-VI, remifentanil, by itself, decreased c-fos expression by 39.4%; for lidocaine alone, the decrease was 58.4%. We did not observe further significant decreases when both remifentanil and lidocaine, or bupivacaine and lidocaine were injected (69.7% and 74.6%, respectively). Our results not only provide strong evidence that activity during the second phase is necessary for maintaining the maximal expression of c-fos in the spinal cord, but also reveal significant regional differences in the central patterns of activity generated during the two phases. These results also confirm our previous reports that c-fos expression is not eliminated when the behavioral manifestation of the noxious stimulus is completely blocked.

Analgesics, Opioid↗
PubMed1997

The limits of social learning: translating analysis into action.

In what respects does public-policy making reflect social learning, drawing lessons from previous experiences and from the experiences of governments in other settings? Starting with an examination of the effect of policy legacies on current policy making, I present a process model of social learning embedded within the larger policy-making process resting at the intersection of the nation's constitutional context, technological change, and political influences exogenous to social learning. The model first distinguishes between the structural and the social learning effects of policy legacies. I then conceptually divide social learning into separate streams of substantive learning and situational learning. The effect that each of these has on policy making depends on the relative position of three categories of participants in the policy-making process (experts, organized interests, and politicians), as well as on the scope of the policy issue being considered (ranging from routine change to major reform). This analysis, with reference to recent health care policy making, reveals the full extent to which social learning is often a decidedly political struggle over ideas and information in which advocates promote lessons that severe their specific interests within a given institutional context and political setting. I consider the implications of social learning for understanding likely policy responses to the rise of market forces in health care.

Economic Competition↗
PubMed1997

Early nociceptive events influence the temporal profile, but not the magnitude, of the tonic response to subcutaneous formalin: effects with remifentanil.

Injection of dilute formalin into the hindpaw produces brief (phase 1) and persistent (phase 2) nociceptive responses in the rat. We recently reported that ongoing peripheral nerve input is required for the expression of behavioral and cardiovascular responses during phase 2. Here we evaluated the contribution of central and peripheral sensitization mechanisms, generated during phase 1, to the magnitude and temporal profile of phase 2. During phase 1, we administered analgesic doses of an ultrashort-acting opioid, remifentanil (i.v. administration from 0-5 min after 5.0% formalin injection), or anesthetic concentrations of halothane (2.1%). Inhibition of phase 1 did not reduce the magnitude of flinching and cardiovascular responses during phase 2, but it did delay their onset and/or termination. Longer remifentanil infusions (0-15 or 0-30 min) produced even longer delays (up to 30 min) in the onset and termination of flinching during phase 2; however, when remifentanil was administered during the early part of phase 2 (15-30 or 15-45 min), it did not prolong the time to termination of phase 2. Continuous infusion (10 mg/kg/hr i.v.) of a peripherally acting opiate antagonist, naloxone methiodide, did not reduce the antinociception produced by remifentanil during phase 1 but almost completely reversed the delay in the onset and termination of phase 2. We conclude that central sensitization mechanisms during phase 1 do not influence the magnitude of phase 2. We also hypothesize that remifentanil interacts with peripheral opioid receptors to impede the formalin-evoked synthesis and/or release of proinflammatory compounds during phase 1 and thus delay phase 2.

Analgesics, Opioid↗