Health needs of adolescents.
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Biomedical subjects
Publications and source records attributed to R L Johnson.
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An ongoing clinical research project on sexual victimization of boys was begun in 1982. The study population is boys aged 12 to 21 years attending an adolescent medicine clinic for reasons other than having been sexually abused. More recently, comparison populations have been obtained from a sexual abuse clinic, from an adolescent medicine clinic for girls, and from a group of adolescent sexual offenders.
The Cholesterol-Lowering Atherosclerosis Study (CLAS) was a randomized, placebo-controlled, angiographic trial testing combined colestipol hydrochloride and niacin therapy in 162 nonsmoking men aged 40 to 59 years with previous coronary bypass surgery. During two years of treatment there was a 26% reduction in total plasma cholesterol, a 43% reduction in low-density lipoprotein cholesterol, plus a simultaneous 37% elevation of high-density lipoprotein cholesterol. This resulted in a significant reduction in the average number of lesions per subject that progressed (P less than .03) and the percentage of subjects with new atheroma formation (P less than .03) in native coronary arteries. Also, the percentage of subjects with new lesions (P less than .04) or any adverse change in bypass grafts (P less than .03) was significantly reduced. Deterioration in overall coronary status was significantly less in drug-treated subjects than placebo-treated subjects (P less than .001). Atherosclerosis regression, as indicated by perceptible improvement in overall coronary status, occurred in 16.2% of colestipol-niacin treated vs 2.4% placebo treated (P = .002).
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Glutamate and aspartate are putative excitatory neurotransmitters in the central nervous system. The present study utilized novel monoclonal antibodies against fixative-modified glutamate and aspartate and polyclonal antisera against the amino acid synthesizing enzymes, glutaminase and aspartate aminotransferase, to analyze the distribution of these amino acids in the rodent midbrain periaqueductal gray. Glutamate-, aspartate-, glutaminase- and aspartate aminotransferase-like immunoreactive neurons, fibers and processes are present throughout the rostrocaudal length of the periaqueductal gray. Glutamate- and glutaminase-like immunoreactive neurons displayed a similar homogeneous pattern of distribution, being localized predominantly to the lateral and dorsal subdivisions of the periaqueductal gray. Co-localization experiments suggest that glutamate and glutaminase are in fact co-contained within the same PAG neurons. Aspartate aminotransferase-like immunoreactive neurons were distributed in a pattern similar to glutamate and glutaminase with the exception that fewer cells were stained in the dorsocaudal and the rostral third of the PAG. Aspartate-like immunoreactive neurons were less numerous than glutamate-like immunoreactive cells and were located in the lateral aspect of the PAG. These results demonstrate a specific and distinct distribution of glutamate and aspartate immunoreactive neurons and support recent data suggesting that glutamate and aspartate serve as excitatory neurotransmitters in the PAG.
The Cholesterol Lowering Atherosclerosis Study (CLAS) is a prospective, placebo-controlled, angiographic trial designed to test the hypothesis that aggressive lowering of LDL cholesterol with concomitant increase in HDL cholesterol will reverse or retard the atherosclerotic process. Specifically, CLAS was designed to determine whether combined therapy with colestipol plus niacin will produce clinically significant change in coronary, carotid, and femoral artery atherosclerosis and coronary bypass graft lesions. To this purpose, 188 subjects were randomized to diet plus drug or diet plus placebo. We report on methodological aspects of planning and evaluating this study, including the choice of the study population, procedures for recruitment, the experimental design including sample size considerations, methods for evaluating outcome, and methods for evaluating compliance to treatment. Comparison of baseline data indicated no significant differences between groups at the time of randomization. Subjects were predominantly male, Caucasian, 54 years of age, 20% above ideal weight, with normal blood pressure. The average age at bypass was 50 years. The average lipids were cholesterol (243 mg/dL), HDL (45 mg/dL), and LDL (168 mg/dL). Finally, the distribution of baseline coronary stenosis was equivalent between the two groups (average number of lesions per subject = 10.6).
In the present study, we measured fiber types and fiber diameters in canine respiratory muscles and examined regional variation within the diaphragm. Samples of eight diaphragm regions, internal intercostals, external intercostals, transversus abdominis, and triceps brachii were removed from eight adult mongrel dogs, frozen, and histochemically processed for standard fiber type and fiber diameter determinations. The respiratory muscles were composed of types I and IIa fibers; no IIb fibers were identified. Fiber composition differed between muscles (P less than 0.0001). Normal type I percent (+/- SE) were: diaphragm 46 +/- 2, external intercostal 85 +/- 6, internal intercostals 48 +/- 3, transversus abdominis 53 +/- 1, and triceps 33 +/- 7. The diaphragm also contained a type I subtype [6 +/- 1% (SE)] previously thought only to occur in developing muscle. Fiber composition varied between diaphragm regions (P less than 0.01). Most notably, left medial crus contained 64% type I fibers. Fiber size also varied systematically among muscles (P less than 0.025) and diaphragm regions (P less than 0.0005). External intercostal fiber diameter was largest (47-50 microns) and diaphragm was smallest (34 microns). Within diaphragm, crural fibers were larger than costal (P less than 0.05). We conclude that there are systematic differences in fiber composition and fiber diameter of the canine respiratory muscles.
To determine the increment in cardiac output and in O2 consumption (Vo2) from quiet breathing to maximal sustained ventilation, Vo2 and cardiac output were measured using an acetylene rebreathing technique in five subjects. Cardiac output and Vo2 were measured multiple times in each subject at rest and during sustained maximal ventilation. During maximal ventilation subjects breathed 5% CO2 to prevent hypocapnia. The increase in cardiac output from rest to maximal breathing was taken as an estimate of respiratory muscle blood flow and was used to calculate the arteriovenous O2 content difference across the respiratory muscles from the Fick equation. Cardiac output increased by 4.3 +/- 1.0 l/min (mean +/- SD), from 5.6 +/- 0.7 l/min at rest to 9.9 +/- 1.1 l/min, during maximal ventilations ranging from 127 to 193 l/min. Vo2 increased from 312 +/- 29 to 723 +/- 69 ml/min during maximal ventilation. O2 extraction across the respiratory muscles during maximal breathing was 9.6 +/- 1.0 vol% (range 8.5 to 10.7 vol%). These values suggest an upper limit of respiratory muscle blood flow of 3-5 l/min during unloaded maximal sustained ventilation.
In an adolescent medicine clinic with more than 1,000 patients during 1982-1984, 11 male adolescents reported a history of sexual molestation by females. This molestation had commonly involved acquaintances and was unlikely to have been accompanied by threats of violence or physical coercion. One-fourth of the victims of both male and female molesters described themselves as sexually dysfunctional, and eight of the victims of male molesters identified themselves as homosexual. Both groups experienced the molestation as highly traumatic.
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Aspartate is a putative excitatory amino acid neurotransmitter that is widely distributed in the CNS. To study its distribution, monoclonal antibodies were produced against beta-L-aspartyl-L-aspartate (beta-Asp-Asp) conjugated to keyhole limpet hemocyanin (KLH) using glutaraldehyde-borohydride. Three monoclonal antibodies, Asp1-3, were obtained with high degrees of selectivity for aldehyde-fixed aspartate. The immunocytochemical staining pattern of rat CNS was found to be similar for all 3 antibodies but differed in some regions from staining patterns produced by Glu1, a monoclonal antibody with high selectivity for a form of amide-linked glutamate. Tissue staining produced by Asp1-3 could be inhibited using aspartate conjugated to carrier proteins. Staining by Asp1 and Asp2 was also inhibited by free small molecules containing aspartate. Specificity of the 3 antibodies was evaluated by enzyme-linked immunoassay (ELISA) as follows: (1) reactivity of antibodies for conjugates of small molecules coated on ELISA plates; (2) ability of free small molecules to inhibit reactivity of antibodies for beta-Asp-Asp/KLH coated on ELISA plates; and (3) ability of conjugates to inhibit reactivity of antibodies for beta-Asp-Asp/KLH coated on ELISA plates. In all 3 types of assays, Asp1 and Asp2 displayed strong reactivity for small molecules and conjugates containing aspartate and little reactivity for small molecules and conjugates containing glutamate or GABA. Asp3 was highly reactive with conjugates containing aspartate using both directed and inhibition ELISA assays. For all 3 antibodies the precise staining pattern varied with the fixative used. Following glutaraldehyde fixation, dense immunocytochemical staining was observed in cerebral cortical neurons, some cerebellar granule cells, hippocampal pyramidal cells, and neurons of the inferior olivary nucleus. In addition, some putative GABAergic neurons, e.g., cerebellar basket and stellate cells, appeared to be stained. In general, acrolein fixation resulted in a more selective staining pattern in the CNS. For example, putative GABAergic neurons were no longer immunoreactive nor were hippocampal pyramidal cells.
Documentation of nutrition counseling effectiveness is essential to reinforce its value in an era of escalating health care costs. Counseling effectiveness can be determined definitively only if dietary assessment is made both before and after intervention. Unfortunately, methods currently available have drawbacks that limit feasibility of routine use. A directly computer-readable Quantitative Food Frequency Analysis method, which eliminates the need for manual data entry, has been developed and instituted at the University of Southern California School of Medicine, Los Angeles, for outpatient counseling. A 1-hour interview, focusing upon "usual" intake, is conducted using pictorial menus for food items. Feedback is available to the patient and health care team immediately. The data base is derived from the National Heart, Lung, and Blood Institute Food Table; the intake of 61 nutrients, including 23 fatty acids, is computed. The computer printout consists of four components: a summary; an alert for foods high in fat, cholesterol, sucrose, alcohol, and/or sodium; a listing of all foods consumed by frequency, accompanied by their nutrient contribution to daily intake; and a bar graph relating current nutrient intake to recommended levels. This document serves as a counseling tool and can support claims for third-party payment.
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Too often, the problem of the pregnant adolescent is approached as if it existed in isolation, disconnected from the remainder of the adolescent's biological and psychosocial environment. Such an approach fails to recognize the interconnectedness of all issues within the adolescent's world, therefore, impeding a successful therapeutic response. In order to administer complete and comprehensive treatment of the problem of teenage pregnancy, the total needs of the pregnant adolescent, the potentially pregnant adolescent and the adolescent male must be addressed. These needs vary with the different stages of adolescent development. During this time in which children learn how to become adults by observing their world and taking cues from the environment, the varying needs are: Early Adolescence--to develop the ability to perceive the long range consequences of their current actions and decisions; to define the boundaries of their independence while relying on major authority figures; and to make important decisions and develop the operational connection between the sex act and birth control. Mid Adolescence--to achieve emancipation from the family and all other authority; to identify with a chosen peer group; to develop an identified sexual identity; and to apply an appreciation for the connection between the sex act and pregnancy to themselves. Late adolescence--to plan for the future and to establish some kind of family. This psychological and social maturational process occurs immediately before, during and after the pubertal growth period. In the United States today, it usually occupies the years between 12 and 21 years.
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The study of uterine metabolism in pregnancy under chronic steady-state conditions has been confined to large mammals and, more recently, to the guinea pig. The pregnant rabbit is of interest because of its short gestation and large litter size. We developed an indirect approach involving retrograde catheterization of the uterine venous drainage, permitting measurement of both uterine metabolic quotients and uterine uptakes. Radioactive microspheres were used to measure blood flow. A large lactate and ammonia efflux from the uterus was found. In the fed state, ketogenic substrates were taken up in small amounts. However, during starvation a significant increase in ketoacid uptake was observed with a concurrent fall in acetate uptake. There was a large glucose/oxygen quotient across the uterus, but the glucose plus lactate/oxygen quotient was comparable to that found in the sheep and guinea pig (0.6 +/- 0.1). It is apparent that in all three species studied under chronic steady-state conditions (sheep, guinea pig, and rabbit) there is a large glucose uptake associated with a net lactate production, and fuels other than glucose and lactate must be used by the uterus.
Conformationally restricted analogues of 2-amino-4-phosphonobutanoic acid (APB,2) were prepared where the structure of APB was incorporated into cyclopentane (3) or cyclohexane (4) rings. Hydrophosphinylation of the appropriate cycloalkenones followed by Strecker amino acid syntheses provided the desired analogues. Assignments of the relative configurations for 3a (trans), 3b (cis), 4a (cis), and 4b (trans) were determined through 13C NMR studies. Compounds 3b, 4a, and 4b possessed low activity as inhibitors of excitatory synaptic field potentials in the rat hippocampal perforant path. Analogues 4a and 4b also showed little activity in displacing [3H]APB from synaptic plasma membranes. The cyclopentyl APB analogue 36, on the other hand, was extremely potent in inhibiting the binding of [3H]APB, possessing an IC50 = 4.7 microM, thus giving further credence to the idea that the APB binding site in the rat brain synaptosomal membrane preparation is not the same as the receptor mediating APB-induced inhibition of the lateral perforant path. Of the four cyclic APB analogues, 3a most resembled APB in its spectrum of biological activity. It showed significant potency (IC50 = 130 microM) in inhibiting lateral entorhinal projections to hippocampal granule cells. Analogous to APB, 3a also showed selectivity for the lateral perforant path over the medial perforant path. Its activity in the radioligand binding assay paralleled its activity in inhibiting the lateral perforant path. It thus appears that 3a comes closest to mimicking the active conformation of APB and suggests that a folded conformation wherein the amino and phosphonate moieties are in a cis relationship to one another may approximate the active conformation of APB.
The synthesis of several analogues of L-prolyl-L-leucylglycinamide (PLG) was carried out in which the glycinamide residue was replaced with the following cyclic amino acid residues: L- and D-prolinamide, (+)- and (-)-thiazolidine-2-carboxamide, L- and D-3,4-dehydroprolinamide, L-azetidine-2-carboxamide, L-piperidine-2-carboxamide, and L-thiazolidine-4-carboxamide to give PLG analogues 2-10, respectively. The ability of these analogues to enhance the binding of the dopamine agonist ADTN (2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene) to dopamine receptors was determined by using bovine brain tissue. All of the PLG analogues synthesized in this study enhanced the binding of ADTN to central dopamine receptors. The percent enhancement of ADTN binding produced by analogues 2,3, and 7-10 at various concentrations was comparable to the percent enhancement produced by PLG. The PLG analogues Pro-Leu-(+)-thiazolidine-2-carboxamide (4), Pro-Leu-(-)-thiazolidine-2-carboxamide (5), and Pro-Leu-L-3,4-dehydroprolinamide (6), however, produced significantly greater enhancement (2-3-fold) in ADTN binding than did PLG.