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Biomedical subjects

J S Walker

Publications and source records attributed to J S Walker.

At least 55 records · Page 3Linked to original sources
PubMed1993

Pharmacokinetics of ibuprofen enantiomers in plasma and suction blister fluid in healthy volunteers.

After a single oral dose of (R,S)-ibuprofen (1200 mg) to five healthy volunteers, paired plasma and blister fluid concentrations of drug were determined by a stereospecific HPLC assay. A pharmacokinetic model that incorporated blister fluid as a separate peripheral compartment adequately characterized the data. The plasma concentrations were consistently higher for (S)-ibuprofen than (R)-ibuprofen in both plasma and blister fluid. No significant difference in the elimination half-life of the enantiomers was observed. Similar to synovial fluid, there were relatively small fluctuations in blister fluid concentrations of both enantiomers. Blister fluid, similar to synovial fluid, therefore behaves pharmacokinetically as a peripheral compartment for drug distribution. This use of skin blisters, which can be sampled repetitively, may therefore prove to be a valuable experimental technique in pharmacokinetic and pharmacodynamic studies of drugs, especially in patients in whom synovial fluid is not available for sampling.

Administration, Oral↗
PubMed1993

Analgesic efficacy of non-steroidal anti-inflammatory drugs in experimental pain in humans.

1. The aim of this study was to establish a simple and reliable experimental pain model that could distinguish the analgesic effects of non-steroidal anti-inflammatory drug (NSAID) treatment from placebo in human volunteers. 2. The reproducibility and reliability over time of subject pain ratings was compared using cutaneous electrical stimuli applied to either the thenar eminence or the ear lobe at varying intensities and modes. Subjects were asked to respond firstly, when the stimulus became clearly sharp and painful ('first pain') and secondly, when the sensation became deep and burning and no further increase in stimulus intensity could be tolerated ('second pain'). 3. Constant voltage stimuli were found to be more reproducible than constant current stimuli. Both phasic (intermittent) and tonic (continuous) stimulation modalities produced 'first' and 'second pain' sensations. The latter sensation was more reproducible, and was perceived as a burning pain which is akin to clinical pain. 4. Analgesics from the NSAID class were found to attenuate reliably only 'second pain' sensations. The analgesic effects of ibuprofen (ibuprofen vs placebo: 0.12 +/- 0.09 vs 0.02 +/- 0.07 volt h(-1), P = 0.03; 95% confidence interval for differences (CI): 0.03-0.18) and diflunisal (diflunisal vs placebo: 0.29 +/- 0.40 vs 0.005 +/- 0.27 volt h(-1), P = 0.0001; CI: 0.168-0.407), respectively, could be distinguished from placebo.

Adult↗
PubMed1992

Pharmacokinetic-pharmacodynamic relationships of morphine in neonates.

Morphine pharmacokinetics and pharmacodynamics (analgesia and sedation) were evaluated after continuous intravenous infusion of morphine in 19 neonates, both preterm and term, whose lungs were ventilated to relieve respiratory distress. Elimination half-life, total plasma clearance, and volume of distribution (mean +/- SD) were 9.6 +/- 3.0 hours, 2.55 +/- 1.65 ml/min/kg (area analysis) or 2.09 +/- 1.19 ml/min/kg (steady-state data), and 2.05 +/- 1.05 L/kg, respectively, and were not significantly different in preterm and term neonates. In neonates with adverse effects of morphine, the plasma clearance was decreased twofold. Mean morphine concentration required to produce adequate sedation in 50% of patients was found to be 125 ng/ml, but concentrations above 300 ng/ml may be associated with adverse effects of morphine. Morphine-6-glucuronide was not detected in the plasma of any neonate, which may explain why neonates require high plasma concentrations of unchanged morphine for sedation.

Female↗
PubMed1992

Prophylactic oral antibiotics for low-risk dog bite wounds.

The use of prophylactic antibiotics in the initial treatment of noninfected dog bite wounds is controversial. All patients with noninfected dog bite wounds who presented to our emergency department (ED) over a two-year period were considered for entry into a randomized prospective study. Patients were excluded from the study if they had any high-risk criteria for infection: puncture wounds, hand or foot wounds, wounds greater than 12 hours old, a history of immunocompromising disorders, or the use of immunosuppressive drugs. Patients in the antibiotic group (n = 89) were treated with local wound care and given either dicloxacillin, cephalexin, or erythromycin orally for seven days. Patients in the control group (n = 96) received local wound care only. All patients had their wounds irrigated with a 1% povidone-iodine solution and debrided and sutured if clinically indicated. All patients were subsequently reevaluated for clinical signs of wound infection. The groups were similar in age, sex, time of delay in seeking treatment, anatomic sites of wounds, depths and types of wounds, and number of wounds requiring suturing. The wound infection rates for the antibiotic and control groups were 1.1 and 5.1%, respectively. This difference was not significant (P = 0.212). There were 36 wounds in the antibiotic group and 37 wounds in the control group that were full thickness. The infection rates for these wounds were 2.8 and 13.5%, respectively. This was not statistically significant (P = 0.132). This study suggests that prophylactic oral antibiotics in low-risk dog bite wounds are not indicated.

Administration, Oral↗
PubMed1991

Kinetics of drug action in disease states. XXXVIII: Effect of body temperature on the convulsant activity of pentylenetetrazol in rats.

The purpose of this investigation was to determine the effect of body temperature on the pharmacodynamics (convulsant activity) of pentylenetetrazol (PTZ). Rats received an iv infusion of PTZ until the onset of maximal seizures, at which time samples of cerebrospinal fluid (CSF), brain, and blood (for serum) were obtained for subsequent determination of PTZ concentrations by HPLC. The PTZ infusion caused a decrease in body temperature of approximately 4 degrees C within 20 min and onset of seizures in approximately 40 min. Compared with animals whose temperature was maintained in the normal range by heating pads, the hypothermic rats required significantly larger doses and higher serum, brain, and CSF concentrations of PTZ to produce seizures. Other rats received an injection of brewer's yeast to produce fever. Then, PTZ was infused 6, 12, or 24 h later when body temperature was elevated by an average of 1.3, 1.1, or 0.4 degrees C, respectively. Compared with control rats, whose temperature was maintained in the normal range by heating pads, moderate hyperthermia had no significant effect on the dose and concentrations of PTZ required to produce maximum seizures. Pentylenetetrazol exemplifies a drug that can produce hypothermia which, in turn, reduces the sensitivity of rats to its pharmacologic action. Unlike the central nervous system (CNS) depressants phenobarbital and ethanol, whose pharmacologic activity in rats is enhanced at elevated body temperature, the activity of the CNS stimulant PTZ is apparently not altered by fever.

Animals↗
PubMed1991

Self-administered intraurethral chlorpromazine: an unusual cause of priapism.

Priapism is a prolonged, painful penile erection unaccompanied by sexual desire and not alleviated by ejaculation. The etiologies of priapism are numerous and diverse. Priapism can be a serious adverse effect of psychotropic medications. The case of a 36-year-old man who demonstrated priapism, 48 hours after inserting a crushed chlorpromazine tablet into the urethral meatus of his penis, is reported. Priapism induced by this route of drug administration has not been previously described. The pathophysiology and treatment of priapism are reviewed.

Adult↗
PubMed1990

Effect of multiple dosing on the analgesic action of diflunisal in rats.

This investigation was designed to compare the analgesic effect of the initial dose of a repetitively dosed non-narcotic analgesic with the analgesic effect of a subsequent dose given 3 days later. To exclude gradual drug accumulation as a variable, the first ("loading") dose was larger than the maintenance doses. Male Sprague-Dawley rats received 100 mg/kg diflunisal i.v. as the first dose and 70 or 75 mg/kg every 12 hours thereafter. The analgesic effect of the first and seventh doses was determined as the pain threshold (voltage) upon electrical stimulation of the tail every 15 to 30 minutes from the third to the ninth hour after dosing. Blood samples for drug assay were obtained at 3 and 9 hours. A control group received injections of solvent for 6 doses and 100 mg/kg diflunisal as the seventh dose. There were no statistically significant differences between the area under the total or free (unbound) drug concentration versus time curves of the first and seventh dose but the average analgesic effect (area under the voltage increase versus time) of the seventh dose was only 28 percent that of the first dose. The areas under the drug concentration and analgesic effect versus time curves of the diflunisal dose given as the seventh injection to the control rats were similar to those produced by the first dose given to the multiple dosed rats. The results of this investigation show that the analgesic effect of a non-narcotic drug decreases substantially during repeated dosing in an animal model of experimental pain. This change in pharmacologic response has the characteristics of functional rather than pharmacokinetic tolerance in that there was no change in the drug concentration profile with time and no effect of the manipulations as such (i.e., repeated pain threshold determinations and blood withdrawals) on diflunisal-induced analgesia. These observations may have important implications for the evaluation and use of non-narcotic analgesics in the management of clinical pain.

Analgesia↗
PubMed1990

Buccal cellulitis.

Buccal cellulitis (BC) is an innocuous appearing infection of the cheek that is found in children and has a high incidence of concomitant bacteremia. Typically, the child is younger than 12 months and has a 2 to 8 hour prodrome of coryza and fever before developing the cellulitis on the cheek. A purplish hue on the cellulitic region is highly suggestive of Hemophilus influenzae bacteremia. The differential diagnosis is reviewed. A complete blood count, blood culture, and cellulitis aspirate culture, should be obtained on all patients with BC. Meningitis may be present despite the lack of meningeal signs. A lumbar puncture should be performed on all children at risk for bacteremic BC. The vast majority of these children are bacteremic and require parenteral antibiotics. A typical case of BC is presented and its management is reviewed.

Amoxicillin↗
PubMed1990

Scapular dislocation (locked scapula).

We report the case of a 19-year-old woman who presented to the emergency department with pain and inability to move her right shoulder after falling backwards and striking it on a cart. Radiographs of the shoulder revealed a dislocated scapula. Closed reduction in the ED was successful. This rare case of scapular dislocation serves to emphasize that a heightened awareness for this injury is necessary if it is to be recognized and treated appropriately. Its treatment and prognosis are reviewed.

Adult↗
PubMed1990

Smooth muscle energetics: testing theories of crossbridge regulation.

Our results indicate that the kinetic "latch" model of Hai & Murphy is not very sensitive to the proportion of ATP assigned to crossbridges relative to that ascribed to MLC phosphorylation/dephosphorylation. Thus the basis for the relatively low efficiency of smooth muscle, attributed to high MLC phosphorylation/dephosphorylation in this model, remains open to question. Moreover, this model, or any model with mixed populations of crossbridges with differing cycle rates and/or high MLC phosphorylation/dephosphorylation rates is unlikely to account for the observed linearity of JATP and stress reported for many smooth muscles. Our studies comparing the heat production of intact and skinned smooth muscle indicate that the ATPase associated with myosin phosphorylation/dephosphorylation is unlikely to be a major factor in the tension cost of intact smooth muscle. Thus it would appear that energetics places considerable constraints on current theories of crossbridge regulation. Our modelling (Paul, 1989) suggests that it may be time to reevaluate Bozler's original hypothesis that a high attachment:detachment rate ratio for smooth muscle actin-myosin interaction may be sufficient to explain the energetics of smooth muscle.

Adenosine Triphosphate↗
PubMed1989

The controversy over radiation safety. A historical overview.

The hazards of ionizing radiation have aroused concern since a short time after the discovery of x-rays and natural radioactivity in the 1890s. Misuse of x-rays and radium prompted efforts to encourage radiation safety and to set limits on exposure, culminating in the first recommended "tolerance doses" in 1934. After World War II, the problems of radiation protection became more complex because of the growing number of people subjected to radiation injury and the creation of radioactive elements that had never existed before the achievement of atomic fission. Judging the hazards of radiation became a matter of spirited controversy. Major public debates over the dangers of radioactive fallout from atmospheric bomb testing in the 1950s and early 1960s and the risks of nuclear power generation in later periods focused attention on the uncertainties about the consequences of exposure to low-level radiation and the difficulties of resolving them.

Environmental Exposure↗