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Biomedical subjects

D B Carr

Publications and source records attributed to D B Carr.

At least 91 records · Page 5Linked to original sources
PubMed1994

Efficacy and safety of nonsteroidal antiinflammatory drugs for cancer pain: a meta-analysis.

PURPOSE: To assess the efficacy and safety of nonsteroidal antiinflammatory drugs (NSAIDs) in the treatment of cancer pain by meta-analyses of the published randomized control trials (RCTs). PATIENTS AND METHODS: Twenty-five studies met inclusion criteria for analysis. Of these, 13 tested a single-dose effect, nine multiple-dose effects, and three both single- and multiple-dose effects of 16 different NSAIDs in a total of 1,545 patients. Baseline pain intensity (when provided) of moderate or higher was indicated in 81% of patients. RESULTS: Single-dose NSAID studies found greater analgesic efficacy than placebo, with rough equivalence to 5 to 10 mg of intramuscular morphine. Pain scores differed insignificantly for aspirin versus three other NSAIDs. Analgesic responses to low- and high-dose NSAIDs suggested a dose-response relationship, but this was not statistically significant. Recommended and supramaximal single doses of three NSAIDs produced comparable changes in pain scores, which indicates a ceiling analgesic effect. Common side effects included upper gastrointestinal symptoms, dizziness, and drowsiness. The incidence of side effects showed a trend to increase with dose, without a ceiling effect, and to increase with multiple doses. Single or multiple doses of weak opioids (WO) alone or in combination (WO/C) with nonopioid analgesics did not produce greater analgesia than NSAIDs alone. Single doses of WO/C analgesics produced more side effects than NSAIDs alone, although both side effect incidence and patient dropout rates were equal when multiple doses were administered. CONCLUSION: These findings question whether the traditional World Health Organization (WHO) second analgesic step (addition of a weak opioid when pain is inadequately treated by a nonopioid analgesic alone) is warranted. A lack of comparable studies precluded testing the hypothesis that NSAIDs are particularly effective for malignant bone pain.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1993

Opioid regulation of parental behavior in juvenile rats.

When exposed to young rats for a period of days, juvenile rats will respond with full parental behavior (FPB: retrieval and grouping of, and crouching over, pups). Because the parental behavior of juveniles is so robust, and because opiates have been shown to be involved in the regulation of parental behavior in adult animals, we examined morphine's ability to disrupt the display of parental behavior in the juvenile animal. In Experiment 1, 25-day-old males and females were administered one of three injection regimens of morphine (MOR), saline (SAL), or naloxone (NAL)--[MOR (5.0 mg/kg) + SAL; MOR + NAL (0.5 mg/kg); or SAL + SAL]--and 1 h later were exposed to three 1- to 6-day-old neonates. Behavior was scored over a 60-min period and animals were considered parental if they responded with FPB for 2 consecutive testing days. Whereas the SAL + SAL and MOR + NAL were not different, MOR + SAL virtually failed to respond to young over a 10-day period. Experiment 2 exposed juveniles to young for a period of days until they displayed 2 consecutive days of FPB. Next, separate groups of juveniles were treated with the same regimen as above. Again, SAL + SAL and MOR + NAL responded rapidly to young, whereas MOR + SAL did not. These data suggest that the display of parental behavior, both its onset (Experiment 1) and maintenance (Experiment 2), appears to be regulated by opiates.

Animals↗
PubMed1993

Assessing older drivers for physical and cognitive impairment.

For older drivers, the automobile is often a vital link in maintaining independence, acquiring goods, and socializing. However, physical or cognitive impairments linked to aging or disease may imperil the driver, passengers, and others on the road. For drivers with multiple medical conditions, physicians can reduce the risk for a crash by identifying and treating illnesses that can impair driving ability. If the conditions cannot be treated, consider modifying the driving environment to reduce the risk, rather than taking away driving privileges. If the risk is unacceptable, seek alternate modes of transportation.

Aged↗
PubMed1992

Basic mechanisms of pain.

It has been well established that pain reflects complex, linked neuroendocrine responses that go far beyond a sensory alarm system. Accordingly, there may be significant medical consequences of inadequate recognition or treatment of pain.

Endorphins↗
PubMed1992

Comparing proxy and patients' perceptions of patients' functional status: results from an outpatient geriatric clinic.

OBJECTIVE: To compare ratings of patients referred for geriatric evaluation and their proxies with respect to patients' ability to perform activities of daily living. DESIGN: Retrospective chart audit. SETTING: University-based Outpatient Geriatric Clinic. PATIENTS: Elderly medicine patients referred to a university-based outpatient geriatrics clinic for the first time. MAIN OUTCOME MEASURES: Modified Katz Physical Activities of Daily Living (PADL) and Instrumental Activities of Daily Living (IADL). RESULTS: With regard to PADLs, patients were generally rated as independent by both patients (91%) and proxies (87%); for IADLs, ratings of independence by both patients (68%) and proxies (51%) were significantly lower. Concordance between patient and proxy ratings was significantly (P less than 0.001) greater for PADLs (92%) than for IADLs (82%). When disagreement occurred, patients consistently rated themselves as more independent than their proxies, especially for IADLs. Moreover, concordance between patients and proxies regarding IADLs was significantly (P less than 0.001) worse for patients who had scores below 24 on the Folstein Mini-Mental State Examination (72%) compared with those scoring 24 or higher (95%). CONCLUSIONS: Patient and proxy ratings were concordant when rating patients' ability to perform PADLs. Moreover, concordance was extremely high on IADLs when patients' Folstein scores were 24 or higher. Concordance with respect to IADLs was relatively poor only among patients with Folstein scores below 24. In that case, patients had a more optimistic view of their independence, compared with their proxies.

Activities of Daily Living↗
PubMed1991

Topographical requirements for delta opioid ligands: presence of a carboxyl group in position 4 is not critical for deltorphin high delta receptor affinity and analgesic activity.

To investigate the role of the carboxyl group in deltorphin molecules, we have synthesized three new analogues in which the acidic amino acid residues in position 4 of the deltorphins were replaced by non-acidic but hydrophilic amino acids residues. The three analogues, [Ser4]-, [Gln4]-, and [Cys4]-deltorphin, all are as potent or more potent than either deltorphin I or II at delta opioid receptors and possess good delta selectivities. The excellent correlation between their in vitro delta receptor potencies and their intrathecal antinociception activity forms a strong argument for involvement of those receptors in spinal nociceptive modulation in the rats.

Amino Acid Sequence↗
PubMed1991

Analgesic activity of a novel bivalent opioid peptide compared to morphine via different routes of administration.

A novel bivalent opioid tetrapeptide, biphalin (Tyr-D-Ala-Gly-Phe-NH)2, was synthesized based on structure-activity relationships. The analgesic activity of biphalin was assessed in comparison to morphine in rats. Drugs were administered subcutaneously (s.c.), intravenously (i.v.) and intrathecally (i.t.). Tail flick and tail pinch were used as tests for analgesia. Biphalin s.c. showed negligible analgesic activity, but when given i.v. produced significant analgesia, although less potent than morphine via this route. In contrast, intrathecal biphalin was more potent than morphine. These results indicate that biphalin has intrinsic activity that is compromised by enzymatic degradation or redistribution in the periphery, properties that may render it useful in exploring analgesic actions of locally applied opioids in the periphery without the likelihood of unwanted central effects.

Amino Acid Sequence↗
PubMed1991

Maternal and fetal plasma atrial natriuretic peptide concentrations during elective caesarean section.

Atrial natriuretic peptide (ANP) is stored in the atrial cardiocyte and is capable of exerting potent, selective, and transient effects on fluid and electrolyte balance and on blood pressure. Because fluid shifts and hemodynamic adjustments occur during parturition, ANP might play a homeostatic role in the parturient and fetoplacental unit. We measured maternal and fetal plasma ANP concentrations in 19 parturients during elective caesarean section. Plasma ANP levels were also measured in seven nonpregnant women of the same age group. The baseline ANP concentration in parturients was significantly higher (29.77 +/- 6.06 pg/ml vs 7.37 +/- 2.1 pg/ml; mean +/- s.e.mean) than in their nonpregnant counterparts. The umbilical artery (UA) ANP concentration was significantly higher than the umbilical vein concentration (91.91 +/- 14.91 pg/ml vs. 40.04 +/- 9.71 pg/ml). Factors under the anaesthesiologist's control may influence maternal and fetal plasma ANP levels. There was a significant correlation between the volume of maternal Ringer's lactate infusion received and maternal ANP concentration. A significant correlation was seen between the total dose of ephedrine administered acutely prior to delivery and the UA ANP concentration. These data suggest that: 1) increased blood volume during pregnancy is associated with increased maternal plasma ANP levels, and 2) the fetus can produce its own ANP, and is thereby capable of responding to ANP stimulating factors.

Anesthesia, Obstetrical↗
PubMed1991

Enhanced potency of receptor-selective opioids after acute burn injury.

Dose-response curves of three receptor-selective opioids were established in a group of nonburned and a group of burned rats. Morphine (mu-agonist), biphalin (mu- and delta-agonist), and U50488H (kappa-agonist) were administered to each group, and analgesia was measured by tail flick latency testing. Each opioid had a significant increase in potency (i.e., a decrease in ED50 values) in the burned (15% body surface area) compared with the nonburned groups. Moderate doses of each drug (i.e., ED50 doses estimated from nonburned group data) in each case augmented stress-induced analgesia in the burned group. Analgesic doses failed to prevent a significant increase in plasma beta-endorphin and corticosterone after larger surface area (25%) burns. Regardless of receptor specificity, opioid analgesic potency is increased acutely after burn injuries.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1990

Antinociception in the rat induced by a cold environment.

Rats placed in a cold environment (4 degrees C) for 2 h had a sustained increase in tail flick latency (TFL) as well as an increase in tail pinch latency (TPch) that was often biphasic with an early peak response at 15 min and a later, often higher, peak at 2 h. Plasma beta-endorphin levels after a modest increase at 5 min (24%) declined throughout the remaining time in the cold. The long-acting opioid antagonist naltrexone had no effect on TFL increases but led to greater increases in TPch (P less than 0.04). In morphine-tolerant rats TFL response was the same as in controls but TPch increases were greater (P less than 0.04). Rats exposed to 2 h of cold for 17 or 18 consecutive days generally developed tolerance to the analgesia of cold, i.e. TFL and TPch increases were diminished; however, the response to morphine on day 18 was the same as in rats never exposed to cold. Adrenalectomy and hypophysectomy led to significantly smaller increases in TFL (P less than 0.02 and P less than 0.001, respectively). The TPch response in contrast, was greater in adrenalectomized (P less than 0.001) and the same in hypophysectomized rats compared to sham controls. An opioid kappa receptor antagonist (Mr 1452) given prior to cold reduced both TFL and TPch response during the first hour. Thus the analgesia induced by cold appeared to shift from an early possibly kappa opioid to a later non-opioid form. The TFL effects seemed to be under hormonal influence while the TPch were not.

Adrenal Glands↗
PubMed1990

Neuropeptides and pain.

Peptides have recently been found to function as neuromodulators or neuromediators within nociceptive pathways at central and peripheral sites. More complex and varied in their chemistry compared to "classical" low molecular weight monoamine neurotransmitters, peptides may nonetheless co-exist with these within a single neuron. The biological activity of a peptide results from an "address" segment that permits receptor binding and a "message" segment that initiates reactions within the cell. Opioid peptides (endorphins) are derived from three precursors and act by altering ionic fluxes of potassium or calcium across cell membranes. Nonopioid peptides active in nociception include calcitonin and its gene-related peptide C.G.R.P., bradykinin, substance P, somatostatin, cholecystokinin, and corticotropin-releasing hormone, among others. Ongoing investigations show significant responses of several peptide systems in experimental models relevant to vascular pain. Although the creation of novel peptide analogues has therapeutic promise, their present clinical use must be cautious in light of reports of neurotoxicity after intraspinal application of some of these compounds in animal models.

Animals↗
PubMed1989

The neuroanatomy, neurophysiology, and neurochemistry of pain, stress, and analgesia in newborns and children.

Beginning with a brief description of mature anatomic pathways and neurotransmitters in the "pain system," this article details their development in the human fetus, neonate, and child. Special emphasis is given to the basic mechanisms and physiologic effects of opioid analgesia. The clinical implications of these data are described, particularly with regard to the maintenance of cardiovascular stability and hormonal-metabolic homeostasis in newborns and children undergoing surgery or other forms of stress.

Analgesics↗
PubMed1989

Comparative effects of the opioids fentanyl and buprenorphine on ventricular vulnerability during acute coronary artery occlusion.

Fentanyl, a mu selective opioid agonist in wide clinical use, raises the ventricular fibrillation threshold in the normal canine myocardium. We have previously shown that this effect is amplified by haemorrhagic stress. In order to determine if mu receptor activation is antifibrillatory during acute myocardial ischaemia, we compared the effects of two mu selective agents, fentanyl and buprenorphine, in open chest chloralose anaesthetised dogs. Each drug was administered intravenously in two doses 1 h apart (fentanyl 30 micrograms.kg-1.dose; buprenorphine 0.3 mg.kg-1.dose). Ventricular fibrillation threshold was measured during right ventricular pacing using the single stimulus technique. The threshold was determined before and during a 10 min left anterior descending coronary artery occlusion. Prior to fentanyl administration, ventricular fibrillation threshold decreased from a control value of 19(SEM 2) mA to 12(1) mA during coronary artery occlusion. After the first dose of this drug an attenuation in the ischaemia induced fall in fibrillation threshold from 23(4) mA to 15(2) mA was observed. After the second dose of fentanyl the decline in fibrillation threshold was significantly blunted at 22(4) mA during control and 18(3) mA during occlusion, p less than 0.05 compared to no drug. In an additional series of experiments atropine sulphate abolished the antifibrillatory action of fentanyl, indicating that vagal efferent activation is responsible for the protective effect of the drug during acute myocardial ischaemia. This is in contrast with its mode of action during haemorrhage, when it enhances vagal afferent inhibition of sympathetic tone, and atropine pretreatment is without effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗