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Biomedical subjects

J A Morrison

Publications and source records attributed to J A Morrison.

At least 73 records · Page 4Linked to original sources
PubMed1986

Pharmacokinetics of mitoxantrone in man and laboratory animals.

Mitoxantrone (NOVANTRONE), an anthracenedione, is a novel anticancer agent with a wide spectrum of antitumor activity. Its anticancer activity is comparable to that of doxorubicin but with apparently significantly reduced cardiotoxicity. The recommended dosage regimen for the treatment of breast carcinoma is 12-14 mg/m2 given intravenously once every 21 days. Intravenously administered mitoxantrone disappears from the plasma of man and laboratory animals with multiexponential kinetics and with the terminal half-life ranging from 38 h to several days. It is rapidly cleared from the plasma by extensive sequestration into the tissues of the rat, dog, monkey, and man. However, redistribution back into the plasma and elimination from the body are slow processes. In both animals and man it is metabolized to the mono- and dicarboxylic acid derivatives, as well as glucuronide conjugates of these acids. Following intravenous administration, it is unchanged mitoxantrone that binds to most tissues. Rats, dogs, monkeys, and man, all eliminate mitoxantrone and its metabolites slowly by both renal and biliary excretion, with the biliary route predominating.

Animals↗
PubMed1986

Identification of human urinary mitoxantrone metabolites.

Two polar metabolites of mitoxantrone, a clinically active antitumor agent, have been isolated and purified from the urine of patients by sequential absorption on glass wool and C18-Sep-Pak cartridges followed by preparative high-performance liquid chromatography. Negative ion chemical ionization mass spectrometry indicated that the two metabolites are the di- and mono-carboxylic acids resulting from oxidation of the terminal hydroxyl groups of the side chain(s). Mass spectral comparison of the urinary metabolites with synthetic compounds confirmed the identification.

Anthraquinones↗
PubMed1986

Patterns of dyslipoproteinemia in selected North American populations. The Lipid Research Clinics Program Prevalence Study.

This article describes the assignment of dyslipoproteinemia (DLP) in several free-living North American populations and presents mean lipid and lipoprotein levels for each type. Dyslipoproteinemic phenotypes were assigned by a modified version of the National Institutes of Health (Fredrickson) phenotyping system. Criteria for assigning phenotypes included age- and sex-specific 5th and 95th percentiles for low-density lipoprotein and high-density lipoprotein cholesterol and total triglyceride, as well as other qualitative and quantitative criteria. Phenotypes IIb, III, I, and V were uncommon, confirming clinical impressions of their frequency. Lipid and lipoprotein levels in specific phenotypes were generally as expected. In the type III phenotype, however, mean cholesterol and triglyceride levels were surprisingly low. Gonadal hormone use, in the form of both oral contraceptives and postmenopausal estrogens, was reported in approximately 30% of women in these populations and was associated with dramatic differences in the frequency of DLP when compared with women not taking hormones. In general, these differences reflected the previously described effects of estrogen and progestins on lipoprotein levels. These data gathered in free-living populations: confirm clinical impressions of the rarity of some phenotypes, focus attention on those phenotypes in which diminished rather than elevated lipoproteins are found, and provide further evidence of the effect of hormones on lipid and lipoprotein levels.

Adolescent↗
PubMed1986

Detection of dyslipoproteinemia with the use of plasma total cholesterol and triglyceride as screening tests. The Lipid Research Clinics Program Prevalence Study.

The efficiency of screening for dyslipoproteinemias associated with hyperlipoproteinemia or with hypolipoproteinemia was examined in 8449 white examinees from the Lipid Research Clinics Prevalence Study. A two-stage lipid screening approach was used. A positive screening test for hyperlipidemia was defined as an elevated level of plasma total cholesterol or triglyceride at both visit 1 and visit 2. A positive screening test for hypolipidemia was defined as a reduced plasma total cholesterol level at both visits. The syndromes of dyslipoproteinemia were defined according to the lipoprotein pattern present at visit 2. When hyperlipidemia was used as a screening tool, generally only about one-half or less of the cases of hyperlipoproteinemia were detected (high proportion of false-negative results). Of all the hyperlipidemic participants, more than 80% had hyperlipoproteinemias (type I, IIa, IIb, III, IV, or V), and such lipid screening therefore provided a lower proportion of false-positive than false-negative results. Most of the participants (greater than 98%) without hyperlipoproteinemia were correctly identified (true negatives). The efficiency of screening for hypolipoproteinemia was in general poorer than that found for hyperlipoproteinemia. Our results were found to be related, in part, to the marked regression to the mean of plasma cholesterol and triglycerides at the extremes of the distributions and to the wide variety of dyslipoproteinemias that can be present within a given range of plasma cholesterol or triglyceride values. The results emphasize the importance of measuring plasma lipoproteins in the patient who is being evaluated for dyslipoproteinemia.

Adolescent↗
PubMed1984

The Collaborative Lipid Research Clinics Program Family Study. II. Response rates, representativeness of the sample, and stability of lipid and lipoprotein levels.

The Collaborative Family Study (1975-1978), the third phase of the Lipid Research Clinics Program Population Studies, covers 2405 probands and 15,693 of their relatives from nine North American communities. This sample was examined for participation differences across race, sex, locality, educational level, and reason for selection. The participation rates were somewhat lower for blacks, younger age groups, and subjects with lower educational levels. The probands' reason for selection into the study had little impact on the participation of probands or relatives. Moreover, based on information gathered at earlier examinations on eligible Family Study probands, the cornary risk factor profile appeared to be similar among participants and nonparticipants . The available longitudinal lipid data on probands indicated general consistency in lipid levels within subjects over short periods of time, in cholesterol even more so than in triglycerides. Among age strata, the younger subjects showed the least intrapersonal stability, especially for triglycerides.

Adolescent↗
PubMed1984

The Collaborative Lipid Research Clinics Program Family Study. IV. Familial associations of plasma lipids and lipoproteins.

Familial associations of total cholesterol, low density lipoprotein cholesterol, triglycerides, and very low density lipoprotein cholesterol were examined in a population-based random sample of 858 white and 73 black probands and their 4,027 white and 245 black relatives from nine North American Lipid Research Clinics. Correlations among biologic relatives were highly significant for total cholesterol and low density lipoprotein cholesterol and to a lesser extent for triglycerides and very low density lipoprotein cholesterol in whites. Correlations for spouses, however, were not significant, suggesting a stronger influence of genes than shared environment in the determination of these traits. Homogeneity of familial correlations across age strata, clinics, and racial groups was examined. In general, correlations were homogeneous across age strata and clinics, and there was no asymmetry in parent-offspring correlations by the sex of the parent or offspring. Racial differences in correlations were not significant except in four of 32 comparisons, with blacks showing weaker correlations than whites in those instances.

Adolescent↗
PubMed1984

Pulmonary changes after exposure to vermiculite contaminated with fibrous tremolite.

Workers exposed to vermiculite contaminated with fibrous tremolite were surveyed for the presence of respiratory symptoms by questionnaire, and for pneumoconiosis by chest radiograph. Pulmonary function was measured by spirometry and single-breath carbon monoxide diffusing capacity ( DLCOsb ). Fiber exposure indexes, expressed as fiber/ml-yr, were derived for each worker from available industrial hygiene data and work histories. The estimated cumulative exposure for the work force ranged from 0.01 to 39 fiber/ml-yr. Discriminant analysis demonstrated significant correlates with shortness of breath and pleuritic chest pain to cumulative fiber exposure. The radiographic changes were limited to pleural changes and involved 4.4% of the population. Parametric and discriminant analysis demonstrated a significant correlation with radiographic changes and cumulative fiber exposure. There were no correlations between spirometry or DLCOsb and fiber exposure. Exposure to vermiculite contaminated with fibrous tremolite can cause pleural changes in occupationally exposed workers. This is supported by the previously identified 12 cases of benign pleural effusions in this working population and the association of pleural radiographic changes and pleuritic chest symptoms with cumulative fiber exposure. The lack of significant parenchymal radiographic, spirometric, and DLCOsb changes most likely reflects the low cumulative fiber exposure.

Adult↗
PubMed1984

Cincinnati Lipid Research Clinic.

A major limitation of the Collaborative Lipid Research Clinic's Family Study and hence, the Princeton School District's Family Study, was the insufficient data gathering relative to environmental influences, particularly nutrient intake, alcohol intake, smoking, habitual physical activity, recent weight gain and loss, etc. (Laskarzewski 1983c). In addition, inadequacies of quantitation of family history further represented major problem areas (Laskarzewski 1982c). Nevertheless, the Princeton School District Family Study had major utility in documenting within-family aggregation of CHD risk factors in children and their young adult parents in an economically variegated, biracial cohort.

Adolescent↗
PubMed1983

Weight change since age 18 years in 30- to 55-year-old whites and blacks. Associations with lipid values, lipoprotein levels, and blood pressure.

To assess associations between current weight, weight at age 18 years, and weight change from age 18 years to ages 30 to 55 years with current levels of plasma cholesterol (C), high- and low-density lipoprotein C (HDLC and LDLC), triglycerides (TG), and systolic and diastolic BP (SBP and DBP), we calculated weight change from self-reported weight at age 18 years and measured weight at ages 30 to 55 years in 308 white and 69 black subjects in a random recall group and 244 whites and 66 blacks in a hyperlipidemic recall group in the Princeton School Study. In random-recall-group whites, mean weight gain over time was greater in men than in women; black women had greater weight gain than black men, and nearly twice the weight gain of white women. Current weight and/or weight gain from age 18 years to ages 30 to 55 years in whites were inversely associated with HDLC level and positively associated with TG level, SBP, and DBP. Similar, but less consistent and significant, trends were observed for blacks. Although weight at age 18 years had no consistent independent explanatory relationship to C, TG, HDLC, and LDLC values, random-recall-group white men who were in the lowest quartile for weight at age 18 years had current levels of C, TG, SBP, and DBP that were all lower than those observed in white men who had been in the upper quartile of weight at age 18 years. Atherogenic increments in TG levels, SBP, and DBP from age 18 years to ages 30 to 55 years are a function, in part, of weight gain during these years.

Adolescent↗
PubMed1983

Familial aggregation of lipids and lipoproteins and early identification of dyslipoproteinemia. The Collaborative Lipid Research Clinics Family Study.

We examined the hypothesis that familial aggregation of lipids and lipoproteins facilitates within-family identification and hyperlipoproteinemia. We studied 841 offspring and 1,236 siblings of normocholesterolemic probands, 833 offspring and 1,194 siblings of hypercholesterolemic probands, 806 offspring and 1,099 siblings of normotriglyceridemic probands, and 877 offspring and 1,108 siblings of hypertriglyceridemic probands in the Lipid Research Clinics Collaborative Family Study Program. As the categorization of probands' hypercholesterolemia or hypertriglyceridemia increased from sporadic, to persistent, to severe, the percentage of hypercholesterolemic or hypertriglyceridemic offspring and siblings increased. Close sibling and parent-offspring lipid and lipoprotein risk factor associations in hypercholesterolemic and hypertriglyceridemic family units during and after the period of shared common-household environment facilitate within-family identification of dyslipoproteinemia and suggest potential sharing of coronary heart disease risk.

Cholesterol↗
PubMed1983

Pharmacokinetics of piperacillin and gentamicin following intravenous administration to dogs.

Piperacillin sodium was administered intravenously to dogs, alone or in combination with gentamicin, twice a day (approximately 5 hr apart) for 36-37 days. The pharmacokinetics of neither drug changed in the presence of the other; however, the percentage of the gentamicin dose recovered in the urine decreased significantly when coadministered with piperacillin. The data demonstrate that interaction between the two drugs in urine is feasible.

Animals↗
PubMed1983

Parent-offspring and sibling body mass index associations during and after sharing of common household environments: the Princeton School District Family Study.

Using the Princeton School Family Study cohort, our specific aim was to determine whether, and to what degree, parent-offspring and sibling associations for measures of body habitus outlast the period of shared common household environment in a single well characterized community. Familial associations of measures in body habitus were assessed in two and three generation kindreds, in parents and their pediatric offspring (less than 20-yr-old), parents and their adult offspring (less than or equal to 20-yr-old), and in pediatric and adult siblings. The cohort included 177 randomly recalled probands and 202 probands from a hyperlipidemic recall group (top decile plasma cholesterol and/or triglyceride). In randomly recalled whites, significant associations of body mass indices in parents and pediatric offspring and in pediatric siblings, and the absence of significant correlations in parents and adult offspring and in adult siblings, emphasize the potency of common household environmental effects relative to within-family similarities for shared body habitus. In whites from the hyperlipidemic recall group, only the mother-pediatric and adult offspring correlations for body mass indices were significant. We speculate that mothers and their offspring from kindreds selected by hyperlipidemic probands are more likely than fathers and their offspring to share eating habits and relative ponderosity, with these communal behaviors outlasting the period of common household environment. Alternatively, and speculatively, in the hyperlipidemic recall group, determinants for ponderosity may be shared more by mothers and their offspring than by fathers and their offspring. Particularly in the random recall group, within-family associations of body mass indices primarily reflect shared common household environments, and probably secondarily, the outcome of genes held in common.

Adolescent↗
PubMed1983

Familial hyper- and hypouricemias in random and hyperlipidemic recall cohorts: the Princeton School District Family Study.

Using the Princeton School Family Study, our specific aim was to estimate the prevalence of familial hyper- and hypouricemia, to estimate the proportion of probands' first-degree relatives who were similarly affected, and to evaluate the contribution of diseases, drugs, and alcohol intake (if any) to uric acid levels. We studied 379 probands and a total of 1928 subjects, 125 and 52 black probands from a randomly recalled group, 147 white and 55 black probands from a hyperlipidemic recall (top decile cholesterol and/or triglyceride) group. Familial hyper- and hypouricemias were arbitrarily identified in those kindreds having at least two first-degree relatives in the same decile as the proband, top or bottom respectively, for serum uric acid. No probands had symptomatic gout. Diseases, drugs, and alcohol intake were not consistently associated with aggregations of high and/or low uric acid levels in families, and had little relationship to uric acid levels in individuals. Of the 177 randomly recalled probands, and of the 55 black probands in hyperlipidemic recall familial hyperuricemia, with concurrent primary hyperlipoproteinemia and hypertension. Familial hypouricemia was present in 1 of 125 white and in 1 of 52 randomly recalled black kindreds, and in 3 of 147 white and 3 of 55 hyperlipidemic recall black kindreds. While familial clustering of hyperuricemia was limited, clustering of hypouricemia was much more marked. Seventy-four and 84% respectively of first-degree relatives of hypouricemic white and black probands had uric acid less than the 50th percentile. In randomly recalled probands and their first-degree relatives there were significant inverse partial correlations between uric acid and high density lipoprotein cholesterol. Inverse associations of uric acid with high density lipoprotein cholesterol and the concurrence of hyperlipoproteinemia and hypertension in hyperuricemic families points to the importance of lipoprotein and blood pressure screening in families with asymptomatic hyperuricemia. The potential ramifications of within-family clustering of hypouricemia need to be further assessed in populations, particularly in regards to uric acid nephrolithiasis.

Adolescent↗
PubMed1983

Longitudinal relationships among endogenous testosterone, estradiol, and Quetelet index with high and low density lipoprotein cholesterols in adolescent boys.

In a 1-year longitudinal study of 19 adolescent boys, our major aim was to assess whether, and to what degree, testosterone, estradiol, Quetelet index, and their interactions related to concentrations of high and low density lipoprotein cholesterol (HDLC, LDLC). During the 1-year followup, mean HDLC and estradiol levels fell and triglycerides, LDLC, Quetelet index, and testosterone levels rose. For large decreases in estradiol, increases in testosterone were associated with decreases in HDLC. These decreases in HDLC were moderated by small decreases in Quetelet index. For boys with small decreases in estradiol, as the changes in testosterone increased, the change in HDLC varied from an increase to a decrease, except in those boys who also had a small decrease in Quetelet index, for whom the change in HDLC was positive. The greatest increases in LDLC were observed in boys having the largest increase in Quetelet index and a small decrease in estradiol; however, as the decrease in estradiol became large, the positive association of Quetelet with LDLC was moderated or nullified. For boys having large decreases in estradiol, the LDLC/HDLC ratio changed from small increments to substantial decrements as testosterone increased. As the decreases in estradiol became smaller, increases in the change of testosterone moderated the decreases in the LDLC/HDLC ratio, and large increases in Quetelet index tended to diminish this moderation. As the change in testosterone increased, the change in triglyceride increased, unless the decrease in estradiol was small. The overall pattern of change of HDLC and LDLC during sexual maturation in boys can be associated with changes in testosterone, estradiol, and Quetelet index.

Adipose Tissue↗
PubMed1983

Familial obesity and leanness.

Using the Princeton School District Family Study cohort, our specific aim was to estimate the prevalence of suspected familial ponderosity and leanness, to provide empirical risk estimates for the proportion of probands' first-degree relatives who were similarly affected, and to estimate the contributions of diseases, drugs and caloric intake to relative obesity and leanness. We studied 379 probands, 125 whites and 52 blacks from a random recall group, 147 whites and 55 blacks from a hyperlipidemic recall group. Suspected familial obesity and leanness were arbitrarily identified in those kindreds with at least two first-degree relatives in the same Quetelet index decile as the proband, top or bottom respectively. Suspected familial obesity was observed in 2.4 percent and 6 percent respectively of random and hyperlipidemic recall group whites. Suspected familial leanness was identified in 2.4 percent and 1.4 percent of random and hyperlipidemic recall whites and in 3.8 percent of randomly recalled blacks. Approximately twice as many as expected white first-degree relatives of top Quetelet index decile probands themselves had top decile Quetelet indices; approximately three times as many as expected first-degree relatives of bottom decile Quetelet index probands themselves had bottom decile Quetelet indices. Nineteen percent and 31 percent of top decile Quetelet index white probands from random and hyperlipidemic recall groups came from families where at least two other first-degree relatives were similarly obese; 18 percent and 20 percent of white random and hyperlipidemic recall group probands with bottom decile Quetelet indices had suspected familial leanness. Nearly all subjects with familial obesity or leanness had no overt metabolic or pharmacological explanations for their body habitus. Within-family clustering of hypertension was common in kindreds with suspected familial obesity and was absent in kindreds with suspected familial leanness. Marked within-family clustering of both obesity and leanness is useful diagnostically; therapeutic intervention to reduce obesity, to be most effective, should be family-wide in the many kindreds which share familial obesity.

Adolescent↗
PubMed1983

Comparison of the maternal and neonatal effects of halothane, enflurane, and isoflurane for cesarean delivery.

The maternal and neonatal effects of 50% O2-50% N2O alone and 50% O2-50% N2O combined with 0.5% halothane, 1.0% enflurane, or 0.75% isoflurane were studied in 42 healthy parturients undergoing general anesthesia for elective primary or repeat cesarean delivery at term. All patients received thiopental and succinylcholine for induction and were intubated and ventilated with a tidal volume of 10 ml/kg at a rate of 10 breaths/min. Two of 12 (17%) patients given O2-N2O alone had recall; none who received a potent inhalation agent had any recall. Blood loss was similar in all four groups. There were no significant differences between groups in induction-to-delivery and uterine incision-to-delivery intervals, the frequency of Apgar scores less than 7 at 1 and 5 min, maternal and fetal blood-gas tensions, acid-base balance, lactate values, and early neonatal neurobehavioral scores at 2-4 h. It is concluded that analgesic concentrations of halothane, enflurane, and isoflurane can be safely added to 50% O2-50% N2O to prevent maternal awareness during general anesthesia for cesarean delivery while maintaining normal maternal and neonatal conditions.

Anesthesia, Inhalation↗