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Biomedical subjects

E M Davidson

Publications and source records attributed to E M Davidson.

At least 19 recordsLinked to original sources
PubMed2001

Antinociceptive and cardiovascular properties of esmolol following formalin injection in rats.

PURPOSE: To assess the role of esmolol, a beta1 receptor blocker, in the modulation of pain in the absence of anesthesia. METHODS: Rats were chronically instrumented to record mean arterial blood pressure (MAP) and heart rate (HR). Animals were divided into three groups. Group 1 [esmolol high (EH) 150 mg x kg(-1) x hr(-1); n = 9], Group 2 [esmolol low (EL) 40 mg x kg(-1) x hr(-1); n = 7] and Group 3 saline (n = 9). Formalin 5% was injected in the rat hind paw. Formalin-induced lifting, MAP and HR were recorded at five minute intervals for 35 min after formalin injection. RESULTS: Formalin was associated with an early (Phase 1; 0-5 min) and late nociceptive response (Phase 2; 10-35 min). Esmolol did not affect Phase 1. Although low dose esmolol had minimum effects on nociceptive Phase 2, it was diminished with high dose esmolol. Formalin induced biphasic increases in MAP and HR. Although esmolol did not affect the initial increase in MAP, high dose esmolol blunted the secondary increase in MAP Both low and high doses of esmolol inhibited formalin-induced tachycardia during the first 30 min. CONCLUSION: Our data suggest that esmolol leads to analgesia and reduction of cardiovascular responses to pain.

Adrenergic beta-Antagonists↗
PubMed2001

Methadone is safe for treating hospitalized patients with severe pain.

PURPOSE: Methadone is still regarded as a second line opioid for patients suffering from severe pain, and is rarely used in hospitalized patients. The infrequent use of methadone is probably due to its long plasma half-life that could lead to accumulation and toxicity. In the present study we report that clinically effective analgesic doses of methadone, given either epidurally or orally, can be used safely for prolonged treatment in hospitalized patients. CLINICAL FEATURES: Over a five-year period we administered methadone at Hadassah Hospital in Jerusalem to 3,954 in-patients with severe pain, 12% of whom were younger than 17 yr. Satisfactory pain relief was recorded in more than 85% of the patients. None of the patients treated with oral methadone developed serious side effects. Three patients, treated with epidural methadone (0.09%), developed a clinically significant respiratory depression. In all three cases, epidural pump failure or pump misprogramming resulted in methadone overdose. None of the children or adults treated with methadone developed addiction during hospitalization. CONCLUSION: Based on its analgesic properties and marked safety profile, we suggest that methadone could be added to the analgesic armamentarium of in-hospital health-care providers. Moreover, methadone could serve as the opioid of first choice in some in-patient populations.

Administration, Oral↗
PubMed1998

Intraplantar injection of dextrorphan, ketamine or memantine attenuates formalin-induced behaviors.

The possible prophylactic effects of local injection of NMDA receptor antagonists that are currently used in humans was investigated in the present study. Intraplantar pretreatment with either 5 mM dextrorphan (DEX), 10 mM memantine (MEM) or 10 mM ketamine (KET) significantly attenuated formalin-induced lifting and licking behaviors, however flinching behavior was not effected. Control experiments indicated that these drug actions could be attributed to local and not systemic effects of the antagonists. We hypothesize that these actions result from blocking NMDA receptors present on unmyelinated sensory axons in the skin. These data suggest that peripheral NMDA receptors contribute to nociceptor activation and can be manipulated to reduce pain of peripheral origin. Since DEX, MEM and KET are currently used in humans and considered clinically safe, they have potential therapeutic value in the treatment of physiologic or pathologic pain states which are induced or maintained by peripheral nociceptor activity. Topical or local application would avoid the side effects that can accompany systemic or intrathecal injection of NMDA antagonists.

Animals↗
PubMed1998

Oral methadone for the treatment of severe pain in hospitalized children: a report of five cases.

OBJECTIVE: Pain relief is still inadequate in many hospitalized patients, especially children in whom suboptimal use of analgesic drugs is still common. In the past 2 years, oral methadone has been used extensively in our institution for treating children with persistent pain from cancer, burns, or trauma who were capable of oral intake and whose pain was not relieved by nonopioid medications. SETTING: Tertiary university hospital. PATIENTS: Of the 70 children treated thus far with oral methadone, five are described in the present report. MAIN OUTCOME MEASURE: Pain relief, acceptability, and side effects of oral methadone in children with pain. RESULTS: Treatment with oral methadone (0.1% in 10% glucose, dose range of 0.2-0.6 mg/kg/day) for time periods of up to 6 weeks resulted in a rapid onset and stable pain relief, with no major side effects. No adverse responses were encountered after discontinuation of treatment. In three of the children, a parent-controlled analgesia regimen was successfully employed. CONCLUSIONS: Oral methadone can be recommended for babies and children who have severe pain that is not alleviated by nonopioid medications and who are capable of oral intake.

Administration, Oral↗
PubMed1997

Peripheral NMDA and non-NMDA glutamate receptors contribute to nociceptive behaviors in the rat formalin test.

The present study demonstrates that local cutaneous administration of either the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist MK-801 or the non-NMDA glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) significantly attenuates formalin-induced nociceptive behaviors. Specifically, pretreatment with either drug reduced the magnitude and time course of lifting and licking behavior in the late phase of formalin pain; however, flinching behavior was not affected. In contrast, post-treatment of formalin pain with either antagonist did not affect lifting and licking behavior, although flinching behavior was mildly attenuated. We hypothesize that these actions result from blocking of peripheral glutamate receptors located on unmyelinated axons at the dermal-epidermal junction. These data suggest that peripheral glutamate receptors on cutaneous axons can be manipulated to reduce certain aspects of pain of peripheral origin. This route of administration offers the advantage of avoiding the side effects of systemic administration.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1988

The racemic metoprolol H2-antagonist interaction.

The effects of concomitant administration of cimetidine and ranitidine on the pharmacokinetics and pharmacodynamics of multiple-dose metoprolol were investigated in 12 normal, healthy male volunteers. The pharmacokinetics of metoprolol were assessed in terms of racemic metoprolol and the individual (R)- and (S)-enantiomers with a stereoselective assay. Ranitidine had no effect on the pharmacodynamics or pharmacokinetics of metoprolol. Although not affecting the pharmacodynamics of metoprolol, cimetidine did produce an increase in the bioavailability of metoprolol through inhibition of enzymes responsible for the first-pass elimination of the beta-blocker. The effect was stereoselective, with the major effect being on the less pharmacologically active (R)-enantiomer.

Adult↗
PubMed1983

Leukotriene B4, a mediator of inflammation present in synovial fluid in rheumatoid arthritis.

Leukotriene B4 (LTB4), generated from arachidonic acid following lipoxygenase activity by a variety of inflammatory leucocytes, has been shown to be present in synovial fluid from patients with active rheumatoid arthritis. It does not persist as such, being converted to less active metabolites. The role of LTB4 as one of the natural mediators of inflammation is discussed.

Adult↗
PubMed1982

Leukotriene B4, an inflammatory mediator in gout.

Leukotriene B4 (LTB4), a metabolite of arachidonic acid and a potent cytotaxin, is generated by human peripheral polymorphonuclear leucocytes (PMNs) exposed to monosodium urate crystals (MSU). The leukotriene is present in gouty effusions in concentrations significantly greater than those found in synovial fluid from patients with active rheumatoid arthritis or osteoarthritis. Further metabolism and biological deactivation of LTB4 by PMNs are partly inhibited by MSU. It is concluded that LTB4 is an important chemical mediator in an acute gouty attack.

Acute Disease↗
PubMed1981

Isomers of leukotriene B4 possess different biological potencies.

Rat elicited polymorphonuclear leucocytes (PMNs), when exposed to the ionophore A23187, release three isomers of leukotriene B4. The three isomers have been purified and tested for their ability to induce the chemokinesis of human PMNs in vitro, the aggregation of rat PMNs in vitro and changes in vascular permeability in rabbit skin in vivo in the presence of PGE2. The results demonstrate that all three isomers are biologically active and that the enzymatically produced isomer, in which the conjugated triene contains one cis and two trans double bonds, is more potent than the two diastereoisomers of LTB4 which contain all trans double bonds in the conjugated triene and which are produced by non-enzymatic hydrolysis.

Animals↗
PubMed1978

Laterality and selective attention in hyperactive children.

Laterality and selective attention were investigated in a group of 20 hyperactive children and their matched controls using a dichotic listening task. There was a strong right-ear advantage for both groups indicating that hyperactive children were not different from normal children in hemispheric specialization for verbal stimuli. In the selective attention experiment hyperactive children were again not different from normal children in their ability either to select the input designated as relevant or to resist the distraction of input designated irrelevant. Both groups gave more correct responses from the right ear than from the left ear, and more intrusions from the right ear than from the left. The results do not suggest abnormalities of lateralization for verbal material or indicate the existence of a selective attentional deficit. It is suggested that such reported deficits may be situation or task-specific.

Attention↗
PubMed1978

PGI2: a potential mediator of inflammation.

PGI2, but not its metabolite 6oxoPGF1alpha, is equivalent in potency to PGE1 as a potentiator of carrageenan, histamine and bradykinin-induced rat paw oedemas. PGI2 must, therefore, be considered as a potential mediator of inflammatory processes.

Animals↗