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Biomedical subjects

D R Hawkins

Publications and source records attributed to D R Hawkins.

At least 37 records · Page 2Linked to original sources
PubMed1987

Major mental illness and childbearing. A role for the consultation-liaison psychiatrist in obstetrics.

Considerable attention has been paid to psychiatric disorders arising in the postpartum period. However, there has been very little systematic study of mental illness during pregnancy. Although quantitatively not a major problem, it can pose several difficulties for mother and fetus. This article reviews the existing literature and along with illustrative cases discusses the management of mental illness related to pregnancy. The relationship between the consultation-liaison psychiatrist and the obstetrician-gynecologist in caring for such problems is emphasized.

Adult↗
PubMed1986

The pharmacokinetics of dichloromethane. I. Disposition in B6C3F1 mice following intravenous and oral administration.

The tissue distribution and metabolism of dichloromethane (DCM; CH2Cl2) was investigated in B6C3F1 mice following iv or oral administration. The route of exposure and the composition of the dosing solution were found to have a significant effect on the pharmacokinetics. Following single iv doses of 10 or 50 mg [14C]DCM/kg dose-dependent metabolism to 14CO2 and 14CO and rapid pulmonary clearance of unchanged 14CH2Cl2 characterized the elimination of DCM from the body. The highest concentrations of 14CH2Cl2 were found in the liver, lung and kidney, with more than 50% of the total radioactivity in these tissues represented by the parent compound. When DCM was administered orally in single gavage doses for 14 consecutive days at treatment levels of 50 mg/kg in water or 500 and 1000 mg/kg in corn oil, rapid absorption and elimination of DCM characterized the treatment in water while distinctly slower trends were found for the doses in corn oil. No observable pharmacokinetic or metabolic effect resulted from repeated oral dosing over the 2-wk treatment period.

Administration, Oral↗
PubMed1986

The pharmacokinetics of dichloromethane. II. Disposition in Fischer 344 rats following intravenous and oral administration.

The tissue distribution and metabolism of dichloromethane (DCM; CH2Cl2) was investigated in Fischer 344 rats following iv or oral administration. The route and level of exposure were found to have a significant effect on the disposition characteristics. A two-compartment model was used to describe the elimination of DCM from blood following single iv doses. The estimates of t1/2,beta were 11.9 and 23.5 min for doses of 10 and 50 mg/kg, respectively, and the disposition rate constants, beta were found to differ significantly at P less than 0.05. When DCM was administered orally (by gavage) in a daily dose of 50 or 200 mg/kg for 14 consecutive days, rapid absorption and distribution to the tissues characterized the disposition. Dose-dependent metabolism to 14CO2 and 14CO and rapid pulmonary clearance of unchanged 14CH2Cl2 were the dominant routes of elimination of DCM from the body following both iv and oral doses. No observable pharmacokinetic or metabolic effect resulted from repeated oral dosing.

Administration, Oral↗
PubMed1985

Reasons for monitoring kinetics in safety evaluation studies.

Studies of the toxicity of a potential new drug form the basis of its preclinical safety evaluation and it is important that these toxicity studies are designed and conducted in a rational manner to permit the reliable interpretation and extrapolation of the resulting data to man. It is proposed that these objectives are more likely to be met with the support of pharmacokinetic data. Generally, toxicity studies include four groups of animals, a control group and three treated groups receiving low, intermediate and high dose levels respectively. In order to assist in the proper selection of appropriate dose levels and to increase the usefulness of the data obtained from toxicity studies, information on the following should be known. Relationship between dose level and the extent of absorption of the test compound. Effect of repeated (chronic) doses on the pharmacokinetics of the test compound. Relationship between the age of the animal and pharmacokinetics of the test compound. Relationship between the dose regimen used clinically and those used in toxicity studies.

Age Factors↗
PubMed1985

Extended sleep (hypersomnia) in young depressed patients.

To test the hypothesis that young depressed patients have prolonged rather than shortened sleep, 14 depressed patients aged 17-25 and age-matched normal control subjects were allowed to sleep as long as they wanted. All subjects increased their sleep over baseline values, but the extended sleep period of the depressed patients was almost twice as long as that of the control subjects. The distribution of sleep stages in the extended period did not differ. The depressed patients had changes in the length of REM periods similar to those of older subjects. The findings suggest an interaction between age, sleep, and depression.

Adolescent↗
PubMed1985

Dietary energy density and frame size effects on composition of gain in feedlot cattle.

Experiments were conducted to evaluate the effects of dietary energy density or genetic background on protein and fat gain of growing cattle. In Exp. 1, 24 Limousin steers were used in a growing-finishing trial. A 2 X 2 factorial arrangement was used with steers randomly allotted to four treatment combinations and fed the following diets: 80% concentrate, high moisture corn-corn silage diet (HI) or a corn silage diet (LO) during both the growing (GRO) and(or) the finishing (FIN) phases. Body composition for both experiments was determined by a deuterium oxide dilution technique. Empty body weight gains were greater (P less than .05) for HI during GRO, FIN and the total trial. Daily protein gains (DPG) were greater (P less than .05) for HI during GRO and FIN, while cattle receiving HI during at least FIN had the greatest (P less than .05) overall DPG. Daily fat gains (DFG) followed the pattern of DPG, being more rapid (P less than .05) for cattle fed HI during either GRO or FIN. Cattle fed the HI diet also tended to be more energetically efficient. In Exp. 2, large frame (LG) and small frame (SM) cattle were used for the evaluation of frame size effects on protein and fat deposition. Steers were individually fed an 80% concentrate, corn-based diet during the entire trial. Average daily gains and daily dry matter intake (P less than .05, P less than .01) were greater for LG, while feed efficiency was similar for both cattle types. Large cattle had greater (P less than .05) DPG than SM cattle, however, DFG were not different. Small frame steers were energetically more efficient (P less than .05), apparently due to composition of gain difference.

Animal Feed↗
PubMed1984

Psychological aspects of patients in germ-free isolation: a review of child, adult, and patient management literature.

Life-threatening medical conditions such as severe combined immunodeficiency disease, leukemia, severe aplastic anemia, radiation injury, burns, organ transplantation, and aggressive administration of chemotherapy often necessitate the isolation of the patient in a protected germ-free environment for weeks or months. This treatment milieu has the effect of extensive psychological and physical isolation from family and staff. A review of the literature was undertaken to investigate the psychological implications of such treatment and to question the possibility that this isolation therapy might produce a unique type of psychological stress. Most authors agree that patients are able to withstand the emotional stress of germ-free isolation and that behavioral changes relate more to the severity of the illness rather than to the isolation. However, there may be inherent stresses related to isolator therapy that can be alleviated by environmental manipulation. Case vignettes are included and patient management in such an environment is outlined.

Adaptation, Psychological↗
PubMed1983

Absorption and elimination of a branched-chain alkylpolyethoxylate surfactant in rats.

Oral doses (100 mg/kg/day) of a 14C-labelled branched-chain alkylpolyethoxylate [( C5H11]2CH14CH2O[CH2CH2O]6H; abbreviated [14C]A12E6) were extensively absorbed from the gastrointestinal tract of rats. During a multiple dosing regime, a proportion of 14C equivalent to one daily dose was excreted each day. This 14C was excreted in urine and faeces in equal proportions; less than 1% of the dose was expired as 14CO2. Almost all the faecal 14C came from the bile and had undergone enterohepatic circulation. After cutaneous application of [14C]A12E6 to rats (8 mg, 333 micrograms/cm2) under occluded conditions, about 25% of the dose was absorbed, mainly during the first 12 h. After dosing by both routes, the A12E6 was biotransformed to several metabolites that were more polar than the parent compound. Less than 15% of the dose was excreted unchanged.

Absorption↗
PubMed1983

Muscle protein turnover in cattle of differing genetic backgrounds as measured by urinary N tau-methylhistidine excretion.

N tau-methylhistidine (N tau MH) was used as an index for muscle protein degradation and this index was utilized to evaluate degradation rates in young growing cattle. Initially, two Charolais crossbred heifers, 12 months of age, were used to measure the recovery of radioactivity in the urine for a 120-hour period after intravenous injection of [14C]N tau MH. Of the radioactivity injected into the animals, 89.7% was recovered after 120 hours. With rate and amount of clearance as the criteria, the excretion of N tau MH in urine appears to be a valid index of muscle protein degradation in cattle. Eight steers of two genetic types were used to evaluate the effect of frame size on turnover rates of muscle proteins with N tau MH as an index. Large frame cattle (LG) excreted more N tau MH per day (P less than 0.03) throughout the trial. Total daily creatinine excretion was less for small frame (SM) cattle (P less than 0.02) showing an increase with time (P less than 0.01) in LG and SM cattle. N tau MH-to-creatinine ratios showed a decline with time. Fractional breakdown rates (FBR) and fractional synthesis rates (FSR) appeared to parallel each other with rates tending to decrease with age. No differences were observed between LG and SM cattle for FBR, FSR or fractional growth rate (FGR).

Animals↗
PubMed1983

The metabolism of salicylidene benzylamine, a pro-drug for salicylate, in rats and dogs.

1. Oral doses of [14C]salicylidene benzylamine were well absorbed by rats and dogs and excreted mainly in the urine (92% dose by rat in 24 h and 84% by dog in 48 h). 2. After 50, 100 and 300 mg/kg oral doses to rats, peak mean plasma 14C concn. (mainly salicylic acid) of 77, 243 and 396 micrograms equiv./ml respectively were reached between 2 and 4 h and maintained at this level until about 7.5 h. 14C was cleared more rapidly from the plasma of male rats than from that of female rats. After 44, 85 and 300 mg/kg oral doses to dogs, peak mean plasma 14C concn. (mainly salicylic acid) of 114, 194 and 320 micrograms equiv./ml respectively were reached at 4 h and then declined with a half-life of 6-7 h. 3. Tissue 14C concn. in both species were greatest at the times of peak plasma 14C concn., but in general were lower than those in the corresponding plasma. 4. The major components in rat and dog urine were salicyl alcohol, salicylic acid and salicyluric acid, the first two being excreted partly as glucuronic acid/sulphate conjugates. After initial hydrolysis of salicylidene benzylamine to salicylaldehyde, approximately equal amounts were reduced and oxidized to the corresponding alcohol and acid respectively.

Animals↗
PubMed1983

The metabolism of the anti-inflammatory drug eterylate in rat, dog and man.

Oral doses of 14C-eterylate were well absorbed by rat and man and excreted mainly in the urine (94% dose by rat in three days and 91% by man in five days). Oral doses to dogs were excreted in similar proportions in both the urine and faeces, although faecal 14C was probably derived in part, from biliary-excreted material. Peak plasma 14C and drug concn. were generally reached between one and three hours after oral doses. In humans, only two metabolites, salicylic acid and 4-acetamido-phenoxyacetic acid, were detected in plasma. The latter was cleared more rapidly than the former and hence plasma salicyclate concn. reached a peak (10.9 and 19.8 micrograms/ml in Subjects 1 and 2, respectively) and initially declined with a half-life of about two-three hours. Plasma 4-acetamidophenoxyacetic acid concn. reached a peak (4.3, 10.0 micrograms/ml, respectively) and declined with a half-life of about one hour. Tissue concn. of 14C were generally greater in dogs than in rats. Highest conc. occurred at three hours in dogs and at one hour in rats. Apart from those in the liver and kidneys, tissue concn. were lower than those in the corresponding plasma. Unchanged drug was not detected in urine or plasma of any species and was rapidly metabolized in human plasma. The major 14C components in human urine were identified as salicyluric acid and 4-acetamidophenoxyacetic acid; minor metabolites were salicylic acid, gentisic acid and paracetamol. These metabolites were also detected in rat urine albeit in different proportions to those in human urine. Dog urine contained less of these metabolites and a major proportion of the 14C was associated with relatively non-polar components. Although salicylic acid and 4-acetamidophenoxyacetic acid were the only major circulating metabolites in man and rat, dog plasma also contained the non-polar urine metabolites.

Acetanilides↗
PubMed1983

Biotransformation of lofexidine in humans.

1. Concentrations of unchanged drug and patterns of radioactive components in urine have been determined by h.p.l.c. following single oral doses of [14C]lofexidine hydrochloride (0.32 mg) to six human subjects. 2. A mean of 12% of the administered dose was excreted in urine as unchanged lofexidine, but the wide range (5-20% dose) indicated significant intersubject variation in the extent of biotransformation. This drug would appear to be metabolized more extensively than the related anti-hypertensive agent, clonidine. 3. The principal metabolite of lofexidine was 2,6-dichlorophenol, which was apparently excreted in urine as two O-glucuronic acid conjugates. The same two metabolites were also the main 14C components circulating in plasma at peak 14C concn. Formation of the phenol from lofexidine probably involved direct O-dealkylation rather than stepwise degradation of the side-chain. 4. Patterns of 3H components in the urine of rats and dogs after oral administration of [3H]lofexidine hydrochloride (0.1 mg/kg) were generally similar to those in human urine.

Adult↗
PubMed1982

A novel conjugate as a major metabolite of bromperidol in man.

The major urine metabolites of the neuroleptic drug, bromperidol, after oral doses to rats and dogs are p-fluorophenylacetic acid and its glycine conjugate resulting from oxidative N-dealkylation. While the same metabolites were also detected in human urine, also present was a major unknown component representing 50% of the total urine metabolites, which apparently was not formed by rats and dogs to any extent. Mass spectroscopic investigations a substituent attached to the tertiary hydroxyl group. The mass spectrum of the metabolite after trifluoroacetylation was consistent with an O-glucofuranosiduronolactone conjugate of bromperidol.

Biotransformation↗
PubMed1982

Effect of the triazolobenzodiazepine estazolam on hepatic drug-metabolizing enzyme activity in rats.

Oral doses of the sedative/hypnotic estazolam (500 mg kg-1 day-1) to rats for 21 days caused statistically significant increases in liver weight, ascorbate excretion, cytochrome P-450 concentrations, and in aniline hydroxylase, ethylmorphine N-demethylase and glutathione S-transferase activities, as did approximately equivalent doses of flurazepam hydrochloride. Histologically, the centrilobular hepatocytes were enlarged. Some of these parameters were also increased after doses of estazolam of 100 mg kg-1 day-1, but not after 5 mg kg-1 day-1, which is about 50-fold greater than a clinical dose. Estazolam was a much less potent enzyme inducer than phenobarbitone under the conditions of these studies.

Animals↗
PubMed1982

Specificity revisited: personality profiles and behavioral issues.

The notion of a connection between illness and temperament goes back at least as far as Hippocrates with his typology of melancholy, sanguine, phlegmatic and choleric personality types. In the 1930s, Dunbar studied large numbers of patients with several chronic diseases from which she derived personality profiles which correlated with the illnesses. Many other studies developed similar correlations. Following the work of Alexander, this approach was deemed superficial. More recently, the description of type A behavior has consistently been shown to correlate with coronary artery disease. The concept of alexithymia is another variant of personality typology. The present status of personality and behavior patterns as markers in psychosomatic medicine are discussed as well as the possible relationship of personality profiles to genetic factors, developmental issues, psychological conflict and other approaches to psychophysiological disorders.

Behavior↗
PubMed1982

The metabolism of the hypolipidaemic drug sultosilic acid in rat, dog and man.

1. Single oral doses of the hypolipidaemic drug [35S]sultosilic acid to rats (40 mg/kg), dogs (40 mg/kg) and man (7 mg/kg) were well absorbed. During three days, means of 59.2%, 58.8% and 61.8% in urine and 37.7%, 31.9% and 19.7% in faeces, were excreted by these species respectively. Most of the dose was excreted during the first 24 h. 2. Peak plasma levels of 35S were generally reached during 1-2 h after oral doses in rats (12 micrograms equiv./ml), dogs (45 micrograms equiv./ml) and two human subjects (15.2 and 10.3 micrograms equiv./ml). In humans, peak plasma levels of unchanged drug (at 1-1.5 h) were 10.5 and 6.3 micrograms/ml. Plasma concentrations of 35S increased almost proportionately to dose in rats following oral doses of 400 and 1200 mg/kg, although in dogs, concentrations were similar at these two dose levels but several times higher than at 40 mg/kg. 3. Tissue concn. of 35S were generally higher in rats than in dogs. Highest concn. occurred at 3 h in rats and 1 h in dogs. Apart from those in the liver and kidneys, tissue concn. were appreciably lower than the corresponding plasma levels. 4. The major radioactive component in dog urine was sultosilic acid. Rat and human urine contained sultosilic acid and also two more polar major metabolites. In male and female rat urine, the proportions of these excretory products differed and the proportions in male rat urine were similar to those in human urine. Sultosilic acid was also the only component detected in dog plasma, whereas rat and human plasma also contained the two urine metabolites. Dog bile contained a conjugate of sultosilic acid. 5. The two metabolites have been identified by mass spectrometry and nuclear magnetic resonance spectroscopy as products resulting from oxidation of the methyl in the p-toluenesulphonyl group. The structures assigned are the corresponding carboxylic acid and the hydroxymethyl derivatives.

Administration, Oral↗