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Biomedical subjects

K W Hindmarsh

Publications and source records attributed to K W Hindmarsh.

At least 19 recordsLinked to original sources
PubMed1994

Perceptions and attitudes with respect to drug use among grades 4 to 6 students: 1992.

Over 2,600 students in Grades 4 to 6 participated, over a 1-year period ending June 30, 1992, in a survey to determine perceptions and attitudes of drug use. While the majority of students did not use drugs, the survey revealed some interesting perceptions. Not all students were aware drugs could be harmful to their health. They indicated using drugs makes you look older, feel good, and get attention. Some felt drugs might be used to be like their friends. This age group of students are obviously very aware of the "drug scene." It is imperative that education start at a very young age.

Alcoholism↗
PubMed1994

Alcohol and drug use by students from western Canada in grades 6 through 12 (1992): have there been any changes over the past five years?

Over 8,000 students in Grades 6 through 12, from Western Canada and the North West Territories were surveyed for the prevalence of licit and illicit drug use over a 1-year period ending June 30, 1992. The results were compared with three previous studies dating back to just over 5 years. While there was a slight decline between 1987 and 1990, the present study reveals a slight reverse in this trend. These results emphasize the need for continued education and perhaps the need for determining the reasons for use by this age group.

Adolescent↗
PubMed1993

Plasma beta-endorphin concentration and xanthine treatment in apnea of prematurity.

Apnea of prematurity is a common problem in neonatal intensive care nurseries. Xanthines are used to treat apnea, but their mechanism of action is not clearly understood. To determine whether xanthines stimulated beta-endorphin (beta-ED) release in preterm infants, plasma beta-ED concentrations were measured in 27 infants with apnea of prematurity. These infants had a mean (+/- SD) birthweight of 1560 +/- 487 g, gestational age 31 +/- 2.5 weeks, and a postnatal age of 7.3 +/- 4.6 d. Twenty-five of the infants were treated with I.V. aminophylline 2.5 mg/kg/dose 4 times daily and 2 were treated orally with caffeine (10 mg/kg). Blood samples were collected prior to and 30 min after treatment with xanthines. Apneic spells greater than 15 sec were recorded and reviewed every 24 h using a Hewlett-Packard Merlin Monitor (Waltham, MA.) system. Infants were then stratified into responders (Group 1, n = 14) and nonresponders (Group 2, n = 13), with responders defined as showing more than 50% decrease in the frequency of apneic spells in the first 24 h of treatment. beta-ED were measured as previously described using a radioimmunoassay technique. In group 1, plasma beta-ED concentration increased significantly, (p = 0.0496) from pre-xanthine (24.4 +/- 12 pg/ml) to post xanthine (34.6 +/- 24 pg/ml) treatment, whereas in Group 2 the concentrations remained the same (23.3 +/- 5 pg/ml) and (22.6 +/- 4 pg/ml). Birthweight, gestational age, postnatal age, and diagnoses in both groups were compared and no significant differences were observed. Interestingly, xanthine treatment caused increased plasma beta-ED release when apneas decreased.

Apnea↗
PubMed1992

Sedative/hypnotic effects of chloral hydrate in the neonate: trichloroethanol or parent drug?

Although the metabolism and pharmacokinetics of chloral hydrate (CH) have been reported, there have been no attempts to correlate CH or its metabolite, trichloroethanol (TCE) with the sedative or hypnotic effects. In order to determine whether plasma concentrations of CH or TCE reflect the sedative/hypnotic effects, a sedation/agitation scale was developed. Based on the results of the present study, the sedative/hypnotic effects of TCE cannot be ruled out completely. However, in the neonate, the parent drug CH seems to have a more important role than has been previously suggested from human research.

Chloral Hydrate↗
PubMed1991

Increased serum sulfate concentrations in man due to environmental factors: effects on acetaminophen metabolism.

Serum sulfate concentrations were determined in volunteers consuming municipal drinking water with varying sulfate contents--77 ppm in Saskatoon and 1157 ppm in Rosetown. The serum sulfate concentrations were subsequently monitored after the administration of single or multiple-dosing regimens of acetaminophen, which undergoes sulfoconjugation, to determine whether sulfate concentrations in serum changed. Average serum sulfate concentrations were 0.35 mmol/L (Saskatoon) and 0.50 mmol/L (Rosetown). Saskatoon volunteers had a significant fall in serum sulfate concentrations during the multiple-dosing regimen. This was not seen in the Rosetown participants. The rates of urinary excretion and renal clearance of sulfate were significantly higher in the Rosetown volunteers. Except for the multiple-dosing t1/2 levels, the Cmax, tmax, AUC and Cl/f of acetaminophen were not significantly different within or between the 2 groups. The excretion of sulfate and glucuronide conjugates of acetaminophen was not significantly different between the 2 groups, but there was a difference within each group with respect to single and multiple-doses. Excretion of the sulfate conjugate fell significantly in the Saskatoon volunteers during the multiple-dose portion of the study, whereas the percentage excreted as the glucuronide increased. The consumption of 15-fold greater sulfate levels in drinking water increased the sulfate concentration in serum. However, this increased concentration did not significantly alter the sulfoconjugation of acetaminophen.

Acetaminophen↗
PubMed1991

Chloral hydrate disposition following single-dose administration to critically ill neonates and children.

Although the metabolism and pharmacokinetics of chloral hydrate (CH) have been studied in healthy adults, no comprehensive studies have been done in neonates and young infants. Major physiological differences between these groups could greatly affect drug disposition. In this study the patient population (22 patients) was divided into three groups according to postconceptual age: group 1 = preterm infants (31-37 weeks), group 2 = fullterm infants (38-42 weeks) and group 3 = toddler-child patients (57-708 weeks). After receiving one 50 mg/kg oral dose of CH, the parent drug and its metabolites were determined by gas chromatography utilizing an electron capture detector. CH, contrary to what has been reported in the adult, was detectable for several hours after oral administration to patients in all three groups. A highly significant negative correlation was observed amongst the three groups for the half-life (t1/2) and area-under-the-curve for 0 to infinity values for trichloroethanol (TCE), the active metabolite responsible for the sedation effect. The t1/2 value for TCE in group 3 (9.67 h) was similar to that reported for the adult population, but in the less mature subjects it was approximately three (group 2: 27.8 h) to four times (group 1: 39.8 h) greater. Trichloroacetic acid had a remarkably long residence time in the study population after a single dose of CH. The concentration of this metabolite failed to decline even 6 days after dose. These issues should be carefully considered when CH administration is contemplated for clinical use in neonates, infants and children.

Administration, Oral↗
PubMed1990

Determination of chloral hydrate metabolism in adult and neonate biological fluids after single-dose administration.

A simple, rapid and sensitive electron-capture gas chromatographic method has been developed for the simultaneous determination of chloral hydrate, trichloroethanol and trichloroacetic acid in biological fluids. The described method is applicable to single-dose pharmacokinetic studies of chloral hydrate in the adult. The method also meets the important requirement of using very small sample volumes and is sufficiently sensitive and reliable for disposition studies in the neonate.

Adult↗
PubMed1989

Diurnal rhythms of cortisol, ACTH, and beta-endorphin levels in neonates and adults.

To determine whether a diurnal rhythm exists in neonates admitted to neonatal intensive care units where there is continuous artificial lighting and periodic nursing and medical care, plasma cortisol, adrenocorticotropin (ACTH), and beta-endorphin concentrations were measured in two groups of infants and in adult human volunteers. As expected, a diurnal rhythm was seen in adults. A diurnal rhythm was also found for cortisol and endorphin levels in neonates (3 to 4 days postnatally) with minimal stress and in infants who were clinically severely stressed. There was not a significant difference between the morning and afternoon concentrations of ACTH in these infants, but the afternoon concentrations were lower than the morning's, as would be expected. We found that a diurnal rhythm does exist in neonates within the first few days of postnatal life and that the continuous lighting and medical and nursing interventions do not interfere with this rhythm.

Adrenocorticotropic Hormone↗
PubMed1989

Chloral hydrate sedation in neonates and infants--clinical and pharmacologic considerations.

Chloral hydrate has been used clinically for over 100 years. There is significant paucity of information regarding chloral hydrate metabolism in neonates and infants. Chloral hydrate and its various metabolites were quantitated in 12 neonates and 2 infants at prescribed time intervals. The analysis of the data indicates accumulation of trichloroacetic acid and trichloroethanol in tissue of compromised infants. There is indirect evidence of competition for hepatic glucuronidation for bilirubin with trichloroethanol in ill preterm infants. Multiple dosing of chloral hydrate in preterm infants should be used with caution and frequent monitoring of serum bilirubin concentrations is indicated in such cases. The mechanism of chloral hydrate metabolism is discussed in detail.

Bilirubin↗
PubMed1987

An evaluation of gentamicin dosing according to renal function in neonates with suspected sepsis.

Aminoglycoside antibiotics are frequently used for the treatment of suspected and confirmed sepsis in the newborn patient. In an attempt to evaluate gentamicin dosing based on serum creatinine concentrations, two groups of neonates were studied (infants less than 34 weeks n = 8 and greater than 34 weeks n = 14). The dosing interval was adjusted per protocol depending on the serum creatinine concentrations. Analysis of the results indicate reasonable therapeutic serum gentamicin trough and peak concentrations in most infants.

Bacterial Infections↗
PubMed1986

The effect of acetaminophen administration on its disposition and body stores of sulphate.

This investigation was designed to investigate the effects of ingestion of multiple therapeutic doses of acetaminophen on the disposition of the drug and on the cosubstrate, sulfate. Nine healthy volunteers and nine outpatients receiving acetaminophen for chronic pain were involved in the study. Volunteers were given a single 650 mg oral dose of acetaminophen. One week later they were given 650 mg of acetaminophen every six hours for five doses. Patients were maintained on their normal treatment and dosage schedules (600 mg every 3 to 8 h) for the study. In healthy volunteers the half-life of acetaminophen after single and multiple dosing was not significantly different. However, the fraction of acetaminophen recovered in the urine as the sulfate conjugate was less and the glucuronide conjugate greater after multiple dosing than after a single of the drug. There was no difference in the percentage recovered as the parent compound between single and multiple dosing. Serum sulfate levels fluctuated over the 6-h period following administration of single and multiple doses of acetaminophen to volunteers. The mean serum sulfate concentration was less after administration of five sequential 650 mg doses of acetaminophen than after a single dose. The renal clearance of inorganic sulfate showed a corresponding decrease. Unexpectedly, patients on chronic acetaminophen therapy exhibited elevated serum sulfate levels (levels higher than the maximum sulfate concentration seen in volunteers).

Acetaminophen↗
PubMed1986

Cerebrospinal fluid and plasma beta-endorphin concentrations in prolonged infant apnea (near-miss sudden infant death syndrome).

Elaboration of beta-endorphins (beta-ED) is implicated in the modulation of respiratory control in infants. Therefore, beta-ED concentrations were measured in paired samples of CSF and plasma in three groups of infants. Group 1 and group 3 were used as controls. Group 2 infants suffered prolonged apnea of infancy (near-miss sudden infant death syndrome) and were successfully resuscitated. Age and weight (mean +/- SEM) in groups 1, 2 and 3 were 8.5 +/- 3 months and 7.2 +/- 1.4 kg, 3.8 +/- 0.7 months and 5.2 +/- 0.6 kg, and 3.4 +/- 0.9 months and 3.4 +/- 0.7 kg, respectively. CSF beta-ED concentrations were found to be significantly elevated in group 2, 67.8 +/- 4.7 pg/ml, when compared to group 1, 29.8 +/- 3.1 pg/ml, and group 3, 46.5 +/- 7.2 pg/ml (p less than 0.01). No correlation was observed with plasma and CSF concentrations in all three groups. beta-ED may play a role in the pathophysiology of prolonged infant apnea (near-miss sudden infant death syndrome).

Apnea↗
PubMed1986

Doxylamine metabolism in rat and monkey.

Metabolites of doxylamine obtained with rat-liver homogenate in vitro and from urine of Wistar rats and squirrel monkeys in vivo were examined. The metabolites were separated by g.l.c., h.p.l.c. and t.l.c., and tentatively identified through interpretation of their mass-spectrometric behaviour. N-Desmethyldoxylamine was identified in vitro while both N-desmethyl and N,N-didesmethyldoxylamine were detected in rat and monkey urine. The N-acetyl conjugates of N-desmethyl and N,N-didesmethyldoxylamine were tentatively identified both in rat urine and in vitro. Only the N-acetyl conjugate of N,N-didesmethyldoxylamine was detected in monkey urine. In addition, nine other metabolites were tentatively identified in rat urine: N,N-dimethyl-2-[1-(?-hydroxyphenyl)-1-(2-pyridyl)ethoxy]ethanamine; N-methyl-2-[1-(?-hydroxyphenyl)-1-(2-pyridyl)ethoxy]ethanamine; 1-phenyl-1-(2-pyridyl)ethanol; 1-(?-hydroxyphenyl)-1-(2-pyridyl)ethanol; 1-phenyl-1-(2-pyridyl)ethane; 1-(?-hydroxyphenyl)-1-(2-pyridyl)ethane; 2-phenyl-2-(2-pyridyl)ethanol; N,N-dimethyl-2-[1-phenyl-1-(2-pyridyl)-2-hydroxyethoxy]ethanamine; doxylamine pyridine N-oxide. The excretion of doxylamine aliphatic N-oxide in rat urine was confirmed by comparison with the authentic synthetic compound.

Animals↗
PubMed1984

Plasma beta-endorphin concentration in infants with apneic spells.

In an attempt to determine whether plasma beta-endorphin (beta-ED) concentrations correlate with occurrence of apnea in preterm infants, measurements were made in three groups of infants. The control group consisted of 11 infants with a mean (+/- SEM) gestational age of 30.5 +/- 0.8 weeks, a mean (+/- SEM) birthweight of 1650 +/- 180 g, and a mean (+/- SEM) postnatal age of 1.3 +/- 0.5 days. Eight infants with apnea, bradycardia, and associated hypotension had a mean (+/- SEM) gestational age, birthweight and postnatal age of 30 +/- 0.9 weeks, 1165 +/- 90 g, and 7.8 +/- 1.9 days, respectively. The third group consisted of eight infants experiencing apnea alone without bradycardia and had a mean (+/- SEM) gestational age, birthweight, and postnatal age of 31 +/- 0.8 weeks, 1380 +/- 125 g, and 2.6 +/- 0.9 days, respectively. The last two groups of infants suffered varying degrees of apnea, but differed in their severity. The plasma endorphin concentrations (+/- SEM) were 26.9 +/- 2, 68.0 +/- 9.0, and 39.6 +/- 2.0 pg/ml, respectively, for the previously described three groups. Significant elevation in beta-ED concentration was observed in the severely apneic infants with bradycardia when compared to the other two groups. The association of increased plasma beta-ED release with severe apneic spells may suggest that these endogenous opiates play a role in the pathophysiology of apnea of prematurity.

Apnea↗