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Biomedical subjects

D R Hawkins

Publications and source records attributed to D R Hawkins.

At least 55 records · Page 3Linked to original sources
PubMed1981

Psychiatric education in Eastern Europe.

Psychiatry and psychiatric education in the Eastern European countries are determined by the cultural practices and tradition of the region and the organizational principles of the U.S.S.R. Medical schools have been separated from the universities and are under the jurisdiction of the Ministry of Health. Soviet psychiatry is less developed in medical education as compared to the West. A unique feature of Soviet medical education is the development of student scientific societies where opportunities exist for more in-depth work in a specialty. Except for a few select students, postgraduate psychiatric training is shorter and less rigorous than in the West. Refresher education at a facility far advanced training is required at 5-year intervals.

Curriculum↗
PubMed1981

The metabolic fate of 3[H]econazole in man.

1. Following single oral doses of 3[H]econazole base (500 mg) to two human subjects, excretion of radioactivity was prolonged, and incomplete after five days (means of 40% and 27% dose in urine and faeces respectively). 2. Plasma concn. of unchanged econazole and total radioactivity attained peak values at approx. the same for each subject (1.5 - 3h), but the former declined much faster than the latter. Most of the 3H in early plasma samples was present as unchanged drug and extractable metabolites, but after 24h concn. of econazole were close to the limit of detection (0.04 ug/ml) and very little plasma 3H was extractable, whereas total 3H concn. were still measurable after five days (mean 1.54 ug/ml). Thus, plasma contained metabolites with much longer half-lives than econazole. 3. The main route of biotransformation of econazole in man involved multiple oxidation of the imidazole ring carbons followed by O-dealkylation and conjugation of the resulting alcohols, probably with glucuronic acid.

Administration, Oral↗
PubMed1980

The absorption and excretion of the peripheral vasodilator 14C-mecinarone, (14C-6809 MD) in rat, dog and man.

Oral doses of the peripheral vasodilator mecinarone (6809 MD), administered as the 14C-compound, were well absorbed from the gastrointestinal tract of rats, dogs and humans. Much of the dose was excreted in 24 by rats and dogs, but more slowly by humans. In 5 days, rats, dogs and humans excreted in the urine and faeces respectively means of 3.3 and 95.9%, 13.2 and 80.3%, and 22.0 and 60.8%. The proportions of radioactivity excreted in urine and faeces after intravenous doses were similar to those after oral doses, means of 3.1 and 85.0% respectively by rats and 16.8 and 78.3% by dogs. Radioactivity present in the faeces was probably mainly excreted in bile; rats (n = 2) excreted a mean of 52.3, 19.8 and 3.9% in bile, faeces and urine after oral doses. Plasma concentrations of radioactivity after oral doses reached a maximum at 1 h in rats (mean 126 ng equiv/ml), at 1 to 2 h in dogs (mean 784 ng equiv/ml) and at 1.5 to 2 h in humans (mean 547 ng equiv/ml. Only a small proportion of this radioactivity (10-30%) represented unchanged drug. When "normalised" for dose/bodyweight differences, those levels were in the ratio 1 : 7 : 32 (rat less than dog less than man). Areas under plasma radioactivity concentration-time curves after oral doses to rats and dogs were about 25% and 53% respectively of those after corresponding intravenous doses. Only about 20% of the radioactivity in the plasma of dogs at 2 min after an intravenous dose represented unchanged drug. These data suggest that 6890 MD was probably rapidly biotransformed in rat, dog and man.

Administration, Oral↗
PubMed1980

Aspects of the metabolism of the peripheral vasodilator mecinarone (14C-6809 MD) in rat, dog and man.

The major proportion of oral doses of 14C-mecinarone was excreted in the faeces by rat, dog and man, and in all species the faecal metabolites were more polar than mecinarone and the O-desmethyl reference compounds. Rat faecal extracts contained two major components each accounting for about 30-40% of the radioactivity. Dog and human faecal extracts contained some mecinarone but also three major, more polar components, two of which corresponded to the rat metabolites. Rat bile contained three major components and dog bile two components. One of the components in both bile samples was shown to be a conjugate of O-desmethyl-mecinarone. Besides mecinarone human urine contained a component corresponding to the phenol resulting from 0-demethylation in the p-methoxycinnamoyl group. The same two compounds were also detected in human plasma. The two major components in rat and dog faecal extracts gave mass spectra identical to mecinarone and the p-hydroxycinnamoyl derivative (O-desmethyl-mecinarone). It is postulated that these thermally-labile metabolites were formed by nucleophilic addition of a substituent to the alpha, beta-unsaturated ketone. It has been demonstrated in vitro that mecinarone forms a glutathione conjugate. The metabolites may be compounds of this type where the glutathione moiety has been degraded in the gastrointestinal tract.

Animals↗
PubMed1980

The distribution excretion and biotransformation of p-dichloro[14C]benzene in rats after repeated inhalation, oral and subcutaneous doses.

1. Following repeated daily whole-body exposure (3 h/day) of rats to atmospheres containing p-dichloro[14C]benzene (10000p.p.m.), or administration of oral or subcutaenous doses (250 mg/kg/day), 24-h tissue concn. of 14C were similar and did not increase after six days dosing, but tended to decrease. 2. After repeated daily atmospheric exposures or oral doses, highest concn. of 14C occurred in fat, kidneys, liver and lungs. Concn. declined rapidly to near or below limits of detection (less than 0.2 p.p.m.) in plasma and tissues at 5 days. After similar subcutaneous doses, tissue concn. declined more slowly. 3. During five days after repeated dosing, most excreted 14C (91-97%) was in the urine. Little was excreted in faeces or expired air. Excretion was more prolonged following subcutaneous administration. After single doses to bile duct-cannulated animals, 46-63% of the excreted 14C was in the bile during 24 h. 4. The pattern of metabolites in urine and bile was similar after each route of administration although there were quantitative differences. Urine extracts contained two major 14C-components, namely a sulphate and a glucuronide of 2,5-dichlorophenol, representing 46-54% and 31-34% of the urinary 14C respectively. Two minor components were identified by mass spectrometry as a dihydroxydichlorobenzene and a mercapturic acid of p-dichlorobenzene. 5. The glucuronide of 2,5-dichlorphenol was the major 14C component in bile (30-42%).

Administration, Oral↗
PubMed1980

The metabolic fate of tizoprolique acid in baboons.

1. After oral administration of the anti-lipolytic drug [14C]tizoprolique acid (2-propyl-5-carboxyl[4-14C]thiazole), to baboons (60 mg/kg), the radioactivity was well absorbed and rapidly excreted. During 6 and 24 h respectively, 60 +/- 25% (S.D.) and 90 +/- 2% were excreted in the urine. 2. Plasma concn. of 14C reached a max. (182 +/- 65, range 85-221 micrograms equiv./ml) at 1-1.5 h after an oral dose, and declined rapidly with an apparent half-life of about 0.5 h. A mean of 77 +/- 7% of the 14C in peak plasma samples was bound to plasma proteins, somewhat less than that of [14C]tizoprolique acid (84 +/- 5%). 3. Tissue concn. of 14 C were highest in an animal killed at 0.5 h after an oral dose, but were lower than those in plasma in all tissues examined except the kidneys. 4. The major metabolite of tizoprolique acid was its glycine conjugate, which accounted for about 80% dose excreted in the 24 h urine. About 2% dose was excreted as unchanged drug. About 70% and 20% respectively of plasma 14C were associated with the unchanged drug and its glycine conjugate during the period 15 min to 4 h after dosing.

Absorption↗
PubMed1980

The metabolic fate of Sormodren (bornaprine hydrochloride) in animals and humans.

1. Single oral doses of the anticholinergic drug [14C]Sormodren to rats (1 mg/kg), dogs (0.3 mg/kg) and humans (0.03 mg/kg) were well absorbed. Excreted in urine and faeces were means of 31 and 70%, 53 and 39%, and 78 and 4% in rats, dogs, and humans, respectively, during five days: excretion was prolonged and still incomplete at five days in humans. 2. Peak plasma levels of 14C (scaled for dose) were generally reached within 1-2 h after oral doses in rats, 49 (ng/ml)/(mg/kg), dogs 290 (ng/ml)/(mg/kg) and humans 410 (ng/ml)/(mg/kg), and declined with half-lives of approx. 5, 12 and 30 h, in these species respectively. Repeated oral doses of [14C]Sormodren to dogs resulted in some accumulation of 14C in the plasma. 3. Tissue concn. of 14C in dogs were generally higher than those in rats, particularly in the brain, lungs and eyes. The tissue distribution of 14C in rats and dogs was consistent with that of a compound readily eliminated by both renal and hepatic routes. 4. Basic metabolites in dog and human, urine and plasma were investigated using a combination of h.p.l.c. and g.l.c.-mass spectrometry. Unchanged Sormodren was not detected in the dog samples and was only a minor component in human urine and plasma. Some metabolites were present as conjugates. 5. A basic extract of enzyme-hydrolysed dog urine (5 mg/kg dose) contained 42% of the urine 14C. The major metabolites in this fraction were identified as three isomers of monohydroxy-N-desethyl-Sormodren and three isomers of monohydroxy-Sormodren, resulting from hydroxylation in the bicyclic ring. The positions of oxidation were not determined. A similar extract from dog urine (0.3 mg/kg dose) contained 26% of the urine 14C and the major metabolites were identified as isomers of monohydroxy-N-desethyl-Sormodren. 6. A basic extract of enzyme-hydrolysed human urine (0.03 mg/kg dose) contained 23% of the urine 14C. The unchanged drug was only a minor component and most of the radioactivity was associated with five isomers of monohydroxy-Sormodren, hydroxylation having occurred in the bicyclic ring. 7. Basic extracts of dog and human plasma only contained about 10% of the plasma 14C. Metabolites were chromatographically similar to the hydroxylated metabolites identified in the corresponding urine samples.

Adult↗
PubMed1979

Aspects of personality associated with irregular sleep habits in young adults.

Studied psychological correlates of irregularity in chronic sleep routines. The California Psychological Inventory (CPI) and Cornell Medical Index (CMI) were administered to two groups of 18 male university students who were categorized as either irregular sleepers or control Ss. The control group was composed of persons who habitually slept from 12-8:00 A.M. Irregular sleepers were defined as those whose retiring and awakening times continuously varied by about 2 to 4 hours. Control Ss scored significantly higher than the irregular group on the CPI scales of Do (dominance), Sy (sociability), Sa (self-acceptance), Sc (self-control), Ac (achievement via conformance), and Ie (intellectual efficiency), but lower on the Fx (flexibility) scale. There were no significant differences between the groups in scores on the CMI or average sleep length recorded over 2 weeks. The present findings indicate that in young adults, personality functioning is related more closely to the regularity of nocturnal sleep routines than to differences in chronic sleep duration. It is postulated that stable or irregular sleeping patterns are largely dependent factors not only of the psychological characteristics that distinguished the groups, but as yet unspecified constitutional and sociocultural antecedents of the human sleep response.

Achievement↗
PubMed1979

The role of psychiatry in Western European medical education.

During 1976-77 the authors studied psychiatric education in Western Europe, visiting university centers in 10 countries. Medical education in various European countries has developed out of different traditions. The significance of these for the present educational systems are discussed and the differences from the U.S. curriculum clarified. Psychiatry until recently in Europe has been dominated by a phenomenological approach. It has not assumed the same importance in the curriculum as in the United States. However, since the student revolts of 1968, there have been major reforms in teaching, including changes in the role of psychiatry in medical education and increased attention to social and psychological factors in health and disease.

Behavioral Sciences↗
PubMed1978

Electrographic analysis of the sleep cycle in young depressed patients.

Electrographic (EEG) patterns of nocturnal sleep were investigated in young psychiatric patients during unipolar depressive episodes. EEG-sleep data was recorded in 20 non-psychotic depressed patients all under 26 years old individually matched with a normal control group. All 20 subjects slept in the laboratory for 1-3 consecutive baseline nights from 12-8:00 a.m. During a subsequent extended condition 14 in each group were allowed to sleep ad-lib. Although the mean total time asleep on baseline nights was about the same between groups (greater than 7.1 hr), the depressives had a statistically significant reduction in REM time, increased transitions into stage 1, but most especially averaged: (a) less stage 4; and (b) more stage 1. Compared with the prior eight-hour night 27/28 subjects among both groups exhibited elevated time asleep during the extended condition, but the patients' mean total 10.3 hr sleep was significantly greater by 1.5 hr than the controls (X = 8.8 hr). Sleep exceeding 9 hr on the ad-lib night was a consistent phenomenon which occurred in significantly more (11/14) young depressed patients contrasted to 4/14 control subjects. These findings indicate that young persons with primary affective disorders do not exhibit nocturnal EEG disturbances of comparable severity to most older depressed patients such as reduced time asleep, increased wakefulness or lowered slow-wave (stages 3 and 4) sleep. Although no direct evidence of symptomatic 'hypersomnia' in these patients was provided, the present results demonstrated that some young persons with clinical depression have the capacity to sleep for sustained periods.

Adolescent↗
PubMed1978

Toxicology studies of linear alkylbenzene sulphonate (LAS) in rhesus monkeys. II. The disposition of [14C] LAS after oral or subcutaneous administration.

The disposition of radioactivity has been studied after administration of single and repeated oral or subcutaneous doses of [14C] LAS to rhesus monkeys. After single 30 mg/kg oral doses the radioactivity was rapidly excreted, mostly during the first 24 h. Means of 71.2% and 23.1% of the dose were excreted in the urine and faeces respectively during 5 days. Similarly, after single 1 mg/kg subcutaneous doses, means of 64.1% and 10.9% were excreted in urine and faeces respectively during 5 days, mostly during the first 24 h. After single oral doses of 30, 150 and 300 mg/kh peak plasma concentrations, at 4 h in all cases, were very similar representing 34, 41 and 36 micrograms/ml respectively. After single subcutaneous doses of 0.1, 0.5 and 1 mg/kg, peak plasma concentrations increased almost proportionately and represented 0.16, 0.72 and 1.13 micrograms/ml respectively. During 7 consecutive daily oral (30 mg/kh/day) or subcutaneous (1 mg/kg/day) doses, there was no accumulation of radioactivity in plasma. Mean peak concentrations and biological half-lives were similar after the first and seventh doses. After 7 doses of [14C]LAS, there was no localisation of radioactivity in any tissue. No unchanged LAS was detected in urine samples after oral or subcutaneous doses. About 5 major radioactive components were detected in urine extracts; all were apparently more polar than LAS, but were not sulphate or glucoronide conjugates.

Administration, Oral↗
PubMed1978

The use of 13C-nmr spectroscopy for the detection and identification of metabolites of carbon-13 labelled amitriptyline.

The antidepressant drug amitriptyline and two of its metabolites, nortriptyline and desmethylnortriptyline, each containing two 13C atoms, have been used to determine the sensitivity and selectivity of 13C-nmr spectroscopy for the detection of unchanged amitriptyline and N-desmethyl metabolites in the urine of animals dosed orally with the labelled drug. The resonance signals from the 13C atoms detected in the 13C-nmr spectrum of entire extract from a control 12 h rat urine sample to which 1 mg of each labelled compound had been added were easily detected, using an instrument accumulation time of 1 h. The 13C-nmr spectrum of an extract of hydrolysed urine from a dog that had received an oral dose of [13C2]amitriptyline (30mg) exhibited signals that could be assigned to metabolites resulting from N-dealkylation and N-oxidation, as well as those bearing the intact amitriptyline side-chain. These assignments were confirmed by analysis of the same extract by g.c.--ms and h.p.l.c.

Amitriptyline↗