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Biomedical subjects

R W Lam

Publications and source records attributed to R W Lam.

At least 109 records · Page 6Linked to original sources
PubMed1988

Preventing neuroleptic-induced tardive dyskinesia in adults and children.

Neuroleptics remain useful in the treatment of schizophrenia, but tardive dyskinesia (TD) is a recognized serious side effect of long-term neuroleptic use in adults and children. Lack of proven effective treatment for TD makes prevention of TD a focus of clinical attention. In order to provide guidelines for the clinician, the literature regarding epidemiological risk factors for TD is reviewed. Clinical strategies for prevention of TD are discussed based on principles of: 1) being aware of risk factors for TD; 2) evaluating neuroleptic treatment; and 3) detecting early TD. The importance of patient participation in the clinical decision for long-term neuroleptic therapy cannot be overstressed.

Adult↗
PubMed1988

Psychiatric morbidity associated with early clinical diagnosis of Huntington disease in a predictive testing program.

Predictive testing for Huntington disease is now possible by using DNA markers close to the mutant gene. Such tests result in an increased or decreased risk estimate as to whether the person tested has inherited the mutant gene. Persons who already manifest subtle signs of the disease but see themselves as presymptomatic will also present to the preclinical testing programs. The authors report a severe psychiatric reaction to a positive clinical diagnosis of Huntington disease in a woman enrolled in a pilot preclinical program who had a history of psychiatric illness and hospitalizations. She is the only one of 60 persons currently enrolled in the program who has had a serious crisis. The authors demonstrate the need for readily available and ongoing counseling services for all persons participating in such a program.

Adjustment Disorders↗
PubMed1988

Atrial natriuretic peptide in the sheep.

To study atrial natriuretic peptide (ANP) physiology in the chronically catheterized pregnant sheep model we developed a heterologous radioimmunoassay for ovine ANP using an antiserum raised against 1-28 human ANP. This antiserum (Tor I) is specific for the aminoterminus of the human ANP molecule and shows little cross reaction with any carboxyterminus ANP fragments. Ovine ANP immunoreactivity was characterized using this antiserum and a commercially available carboxyterminus ANP antiserum obtained from Peninsula Laboratories. Each antiserum detected 2 peaks of immunoreactivity in ovine atrial extracts chromatographed on a Biogel P-10 column. The minor peak migrated at a position close to 125I-human ANP whereas the major peak represented a larger molecular weight species of ANP. Examination of gel filtration eluates of ovine plasma extracts showed one immunoreactive ANP peak using the Tor I assay system and 2 peaks with the Peninsula Laboratories assay. Plasma immunoreactive ANP levels were determined in 9 sheep using both radioimmunoassay systems. Mean (+/- SEM) levels were similar using the Peninsula Laboratories and the Tor I assay systems (57 +/- 8 pg/ml versus 43 +/- 4 pg/ml, P greater than 0.05). Using the Tor I antiserum, fetal plasma immunoreactive ANP levels were found to be significantly higher than maternal levels (188 +/- 17 versus 48 +/- 8 pg/ml, P less than 0.01) whereas pregnant and nonpregnant adult sheep had similar plasma immunoreactive ANP levels (48 +/- 8 versus 43 +/- 4 pg/ml, P greater than 0.05). Disappearance curves of synthetic human ANP from the plasma of maternal and fetal sheep were assessed using both immunoassay systems and found to be similar.

Animals↗
PubMed1987

Plasma atrial natriuretic peptide response to volume expansion in the ovine fetus.

Atrial natriuretic peptide is a potent diuretic and vasorelaxant peptide secreted from the cardiac atria of adult mammals in response to increased intravascular volume. In sheep, fetal plasma levels of atrial natriuretic peptide are significantly greater than maternal levels, but the factors that control fetal release of atrial natriuretic peptide have not been defined. The present studies were conducted to determine whether the fetus responds to increased intravascular volume by atrial natriuretic peptide secretion. The mean (+/- standard error of the mean) atrial natriuretic peptide of basal fetal plasma (115 +/- 24 pg/ml) in chronically catheterized ovine fetuses (131 +/- 1 days' gestation) was significantly greater than atrial natriuretic peptide levels of basal maternal plasma (56 +/- 12 pg/ml). In response to successive 30-minute intravenous infusions of 0.9% saline solution at 0.5 and 1.0 ml/kg/min, fetal plasma atrial natriuretic peptide significantly increased to a maximum of 409 +/- 72 pg/ml during the high-dose saline infusion and returned to 234 +/- 83 pg/ml during a 30-minute recovery period. The increase in fetal plasma atrial natriuretic peptide was significantly correlated with the volume of saline solution infused (r = 0.68). During the saline infusion, a significant increase in fetal blood volume and heart rate was noted. Fetal blood pressure, maternal plasma levels of atrial natriuretic peptide, and fetal and maternal plasma osmolality remained unchanged. Despite elevated basal levels of plasma atrial natriuretic peptide, the third-trimester ovine fetus responds to increases in intravascular volume with a further increase in atrial natriuretic peptide secretion.

Animals↗
PubMed1987

Epidermal growth factor acts as a corticotropin-releasing factor in chronically catheterized fetal lambs.

Epidermal growth factor (EGF) has been reported to stimulate adrenocorticotropin hormone (ACTH), growth hormone and prolactin secretion from pituitary tissue in vitro, and in large doses evokes ACTH secretion in adult sheep in vivo. In order to assess a possible role for EGF in the pituitary hyperfunction characteristic of the in utero fetus, we measured changes in plasma immunoreactive ACTH concentrations after acute administration of saline, purified mouse EGF or synthetic ovine corticotropin releasing factor (CRF) to chronically catheterized fetal sheep. Both CRF and EGF were associated with increases in plasma immunoreactive ACTH concentrations. Peak values 60 min after 10-micrograms injections of either EGF or CRF increased from baseline ACTH values of 61 +/- 11 pg/ml to 191 +/- 37 and 178 +/- 25 pg/ml, respectively. Dose-response studies indicate that at low doses (less than 20 micrograms) EGF is as potent a stimulus for ACTH release as CRF. EGF infusion was not associated with detectable changes in circulating CRF, catecholamines, arginine vasopressin levels, or plasma growth hormone concentrations. We speculate that EGF may be important in the regulation of pituitary function in the developing mammalian fetus.

Adrenocorticotropic Hormone↗
PubMed1986

Blunted response of maternal ovine placental lactogen levels to arginine stimulation after single umbilical artery ligation in pregnant sheep.

Ovine placental lactogen levels in the maternal circulation are significantly reduced after single umbilical artery ligation in pregnant sheep. We report the ovine placental lactogen response to high-dose amino acid stimulation in four ewes with fetuses that underwent single umbilical artery ligation and six control ewes with fetuses that underwent sham operation. After maternal infusion with 50 gm of arginine in 350 ml of distilled water, mean ovine placental lactogen levels in ewes with fetuses that underwent single umbilical artery ligation increased by 170%, while mean levels in control ewes increased by 294%. Maternal infusions with hypertonic saline solution of osmolality and volume equal to those of the arginine solutions failed to increase maternal ovine placental lactogen levels. Fetal well-being, both during and after the maternal arginine infusions, was confirmed by unchanged fetal arterial blood gases and catecholamines. The ovine placental lactogen levels in the fetal circulation were not altered by maternal arginine infusion. These data suggest that the correlation between maternal ovine placental lactogen levels and functioning placental mass may be enhanced by arginine stimulation. The possible use of this provocation of placental lactogen levels as a test of placental function in clinical practice is discussed.

Animals↗
PubMed1986

Effect of thyroid status on lung and heart beta-adrenergic receptors in fetal and newborn sheep.

The effect of altered thyroid status on the development of beta-adrenergic receptor (BAR) density and affinity was investigated in ovine fetal and newborn heart and lung. Fetal (119-121 days gestation) and newborn (2-3 days of age) sheep underwent either thyroidectomy alone, thyroidectomy plus infusion of a large dose of T3 or sham operation. Eight days later BAR were measured in heart and lung using the tritiated radioligand dihydroalprenolol. There was no apparent effect of altered thyroid status on fetal heart or lung BAR density or affinity. In contrast, the newborns thyroidectomized and infused with T3 had a 96% increase in heart BAR density and an 83% increase in lung BAR compared to the thyroidectomized only or sham-operated newborns which were similar. These results suggest that in the near term ovine fetus heart and lung tissue BAR are neither dependent on nor responsive to thyroid hormones, whereas in the newborn period heart and lung BAR are highly responsive to thyroid hormones.

Animals↗
PubMed1986

Autoimmune sympathectomy in fetal rabbits.

An autoimmune model for in utero immunosympathectomy of fetal rabbits was developed. Non-pregnant, female rabbits were injected with purified nerve growth factor and then bred after confirmation of high titers of anti-nerve growth factor antiserum. Fetuses were delivered and sacrificed at 27 and 31 days gestation and tissue norepinephrine concentration was used as an index of sympathetic innervation. There were significant reductions in tissue norepinephrine at both gestational ages. At 31 days there was a 32% reduction in lung norepinephrine concentration, 46% in the heart and 60% in brown adipose tissue. Corresponding reductions at 27 days were 68% for lung, 44% for heart and 49% for brown adipose tissue. Adrenal catecholamine content was unaffected but para-aortic gland catecholamines were slightly increased. Pulmonary beta adrenergic receptors showed a 30% up regulation in response to dennervation. Carcass weight was reduced 15% to 11% in the dennervated animals. These results demonstrate that dependence of organ sympathetic innervation on nerve growth factor can be demonstrated as early as 27 days gestation. This is a useful model to study the timing and dependence of organ sympathetic innervation on nerve growth factor and the factors which regulate this dependence.

Animals↗
PubMed1985

Neonatal adaptation: greater sympathoadrenal response in preterm than full-term fetal sheep at birth.

A marked increase in sympathoadrenal activity at birth has been described in animals and humans. Studies to determine whether the magnitude and duration of the catecholamine surge at birth in preterm lambs is similar to full-term lambs were undertaken using an acutely exteriorized fetal lamb. To maintain a physiologically stable preparation, all preterm lambs were given natural sheep surfactant intratracheally before the first breath. Base-line catecholamine values were similar in the full-term and preterm lambs. After umbilical cord cutting there was a marked increase in circulating norepinephrine (NE) and epinephrine (E) in both full-term and preterm animals. The preterm animals exhibited a delayed but exaggerated elevation of both NE and E relative to term animals. The peak preterm value for NE (3.8 +/- 1.2 ng/ml) occurred at 60 min and exceeded the peak NE value 1.2 ng/ml observed at 15 min in full-term animals. The peak E concentration in preterm animals was over 9 ng/ml between 2 and 3 h of age, whereas full-term animals reached a peak value of 1.1 ng/ml at 5 min. Heart rate and blood pressure rose abruptly to peak values by 5-15 min in full-term animals. Changes in heart rate and mean arterial pressure were less profound and more gradual in preterm animals. Full-term animals also demonstrated a five-to sevenfold increase in plasma free fatty acids, whereas concentrations in preterm animals increased only two- to threefold. There was a similarly blunted response in blood glucose in preterm animals. The catecholamine surge at birth may be an important adaptive phenomenon with physiological implications.

Adaptation, Physiological↗
PubMed1984

Fetal catecholamine release with preterm delivery.

Neurosympathetic system activity at birth was studied by measuring umbilical arterial plasma catecholamine concentrations in 36 preterm fetuses. Umbilical arterial catecholamine concentrations were correlated with blood gas status, mode of delivery, fetal sex, and fetal heart rate patterns. Significant correlations were observed for plasma norepinephrine and epinephrine versus fetal pH and PO2 and for plasma dopamine versus pH but not PO2. These catecholamine relationships to acidosis and hypoxia were similar to those of our previously published data for term fetuses. Norepinephrine and dopamine concentrations were similar in both preterm and term fetuses; however, epinephrine levels were significantly greater in preterm fetuses than in term fetuses. Increased concentrations of norepinephrine, epinephrine, and dopamine were observed in association with abnormal fetal heart rate patterns. There was no significant effect of fetal sex on the catecholamine secretory response. Similar cord catecholamine concentrations were observed following vaginal and cesarean section delivery, the latter with and without labor. These results indicate that the preterm fetus, like the term fetus, responds to stress at delivery with a graded catecholamine release. The observation of greater epinephrine concentrations in preterm fetuses than in term fetuses may reflect increased secretion or decreased clearance of epinephrine.

Dopamine↗
PubMed1984

Catecholamine physiology in the ovine fetus. I. Gestational age variation in basal plasma concentrations.

Fifty-five ewes with chronically catheterized singleton gestations were studied to assess changes in basal concentrations of fetal catecholamines with increasing gestational age. All pregnancies were time dated, and measurements of catecholamines were conducted at least 5 days after placement of fetal catheters when fetal metabolic parameters had normalized. Plasma concentrations of catecholamines were measured by radioenzymatic assay. Additionally, fetal heart rate (FHR) and corrected mean blood pressure were analyzed in 32 of the fetuses for correlation with plasma levels of catecholamines. Multiple regression analysis revealed significant inverse correlations of fetal plasma concentrations of catecholamines with gestational age, as follows: norepinephrine (p less than 0.001), epinephrine (p less than 0.05), and dopamine (p less than 0.01). FHR correlated inversely with gestational age (p less than 0.001) and positively with circulating levels of norepinephrine (p less than 0.001).

Animals↗
PubMed1984

Catecholamine physiology in ovine fetus. II. Metabolic clearance rate of epinephrine.

This study measured the metabolic clearance rate (MCR) of epinephrine (E) in 13 chronically catheterized fetal lambs between 120 and 145 days gestation. The E-MCR was determined by a constant infusion method at an E infusion rate of 0.1 microgram/kg estimated fetal wt. Fetal and maternal arterial blood samples were taken for measurements of catecholamine levels, pH, blood gases, and glucose. There was a significant positive correlation between gestational age and E-MCR (r = 0.87, P less than 0.001). The E production rate in fetuses less than 132 days (n = 6) (1,234 +/- 301 pg/min) was not significantly different from fetuses greater than or equal to 132 days (n = 7) (1,195 +/- 242). Catecholamine infusion resulted in a decrease in pH from a control value of 7.37 +/- 0.01 to 7.31 +/- 0.01 by 15 min of infusion, but there were no significant changes in fetal heart rate or blood pressure. The mean fetal plasma glucose concentration increased 45% above base line at 15 and 20 min and 65% above base line by 30 min of catecholamine infusion. After 60 min of infusion plasma norepinephrine (NE) increased from 380 +/- 60 to 520 +/- 75 pg/ml and plasma dopamine from 100 +/- 20 to 240 +/- 50 pg/ml (both P less than 0.05). These results indicate that E-MCR increases with maturation in the absence of a change in basal E production.

Animals↗
PubMed1984

[Adrenal epinephrine and the regulation of pulmonary surfactant release in neonatal rabbits].

Adrenergic mechanisms influence surfactant metabolism; however the nature and importance of catechol-mediated regulation is unclear. We designed experiments to assess the role of endogenous adrenal epinephrine (E) synthesis in neonatal alveolar surfactant release. We administered the experimental adrenal epinephrine synthesis inhibitor SKF 29661 to pregnant rabbits to reduce fetal adrenal E content. Surfactant release was measured as total alveolar phosphatidylcholine (PC) content recovered by a thorough alveolar wash performed on animals sacrificed at birth and at 1 h of age. At a maternal dose of 100 mg/kg/day, SKF 29661 caused a 57% reduction in fetal adrenal E content (p less than .01), which was associated with a 40% reduction in alveolar PC at birth and a 23% reduction in alveolar PC at 1 h of age (p less than .01). Moreover, adrenal E correlated positively with total alveolar PC content (p less than .001). These results suggest that in the neonatal period, the ability of the fetal adrenal gland to synthesize E for secretion plays a role in the regulation of pulmonary surfactant release.

Adrenal Glands↗
PubMed1984

Iodination of thyroliberin by use of Iodogen.

In this method of labeling thyroliberin for radioimmunoassay, 1,3,4,6-tetrachloro-3 alpha,6 alpha-diphenylglycoluril (Iodogen) is used as oxidant. By cation-exchange chromatography and in response to antibody, thyroliberin so labeled behaved similarly to that produced by the conventional Chloramine-T method. Major advantages of the Iodogen method are its reliability, simplicity, and higher yield of stable RIA label in its most convenient (diiodinated) form.

Chromatography, Ion Exchange↗
PubMed1983

Identification and partial purification of phenylethanolamine N-methyl transferase in the developing ovine lung.

Phenylethanolamine N-methyl transferase (PNMT), the terminal enzyme in epinephrine biosynthesis, was identified in fetal and newborn ovine lung. The ovine lung PNMT demonstrated the appropriate substrate specificity and affinity (Km, 9 x 10(-6) M). Although some homology between adrenal and lung PNMT was observed on polyacrylamide gel electrophoresis, the lung PNMT differed in its migration on ion exchange chromatography and was not inhibited by pharmacologic inhibitors active against the adrenal enzyme. Activity increased from a mean of 132 pmole/(mg protein . h) x 10(-3) at 0 days gestation to 326 pmole/mg protein . h) x 10(-3) in newborn animals between 1-4 days of age (r = 0.571, P less than 0.05). The levels of N-methylating activity in extraadrenal tissues were relatively low; lesser but significant N-methylating activities were demonstrated in brown adipose tissue and myometrial tissues. Adrenal gland activity was 1000-fold greater than lung activity expressed on a per mg protein basis and 250-fold greater expressed per mg wet weight.

Adrenal Glands↗
PubMed1982

Determining priorities of the Georgia Student Society for Medical Technology: results of a survey.

The opinions of student laboratory personnel regarding the objectives of their student organization were obtained and analyzed. By documenting their perceptions in this manner, the use of unspoken assumptions accompanying formulation and change in organizational direction has been abolished. Additionally, this has allowed them to acquire an understanding of the current perceptions held by their peers, and of the goals cited for making their professional organization more responsive to current and future needs. As a result, it is anticipated that motivation will be heightened and that professional unity, identity, growth, and development will improve.

Georgia↗
PubMed1981

Sex differences in lung and adrenal neurosympathetic development in rabbits.

To assess the possible mechanism for the increased incidence and severity of the respiratory distress syndrome (RDS) in male versus female infants, we studied neurosympathetic development in the lung and adrenal glands in male and female fetal and newborn rabbits. Tissue levels of catecholamines, norepinephrine (NE), epinephrine (E), and dopamine (DA) were measured using a sensitive radioenzymatic assay. Beta adrenergic receptor development in the lung was studied using the tritiated radioligand dihydroalprenolol. Neurosympathetic innervation of the lung was assessed by measuring tissue NE levels, which increased gradually from 27-day fetuses to 8-day-old newborns. Sex differences were not significant. Lung beta-receptor number was significantly elevated in females as compared with males at each gestational age and throughout the neonatal period (p less than 0.005). Adrenal gland content of E, NE, and DA increased exponentially with advancing developmental age (each p less than 0.005). Adrenal E was significantly (p less than 0.01 elevated in female as compared with male fetuses, as was the proportion of E. Adrenal NE and DA were similar in male and female fetuses. Sex differences were not significant in the newborn animals. The significant relative delay in adrenal medullary and lung beta-receptor matration may relate to the male susceptibility to neonatal morbidity and neonatal RDS.

Adrenal Glands↗