USP standards and activities affecting pharmacy practice.
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Biological Availability↗
Biomedical subjects
W L Paul
Publications and source records attributed to W L Paul.
Time-resolved fluoroimmunoassay compared with radioimmunoassay of luteinizing hormone.
OBJECTIVE: To determine if fluoroimmunoassay (FIA) of serum luteinizing hormone (LH) is more useful clinically than a conventional radioimmunoassay (RIA) because it has been suggested that FIA closely reflects biological activity. DESIGN: Comparison of serum LH measurements by RIA and FIA during various perturbations in normal ovulatory women and in women with polycystic ovarian syndrome (PCOS). SETTING: Normal ovulatory subjects were healthy volunteers and women with PCOS were untreated and newly diagnosed outpatients in our Reproductive Endocrinology/Infertility Clinic, Women's Hospital, at the Los Angeles County+University of Southern California Medical Center. PARTICIPANTS: Fifty-three normal ovulatory women, ages 20 to 35, and 27 women with PCOS, ages 21 to 35. All were in good health and received no other medications during the study period. RESULTS: Fluoroimmunoassay of serum LH reflected status of known altered bioactivity better than with a conventional RIA. This was most evident during conditions of gonadotropin suppression and in patients with PCOS. An excellent correlation was found between values of FIA and RIA. CONCLUSIONS: The measurement of LH by FIA is clinically useful, specifically when a change in biological activity of LH is sought.
Adult↗
Lp(a) lipoprotein: relationship to cardiovascular disease risk factors, exercise, and estrogen.
OBJECTIVE: Lp(a) lipoprotein is a distinct lipoprotein particle that recently has been found to be associated with cardiovascular disease. A study was conducted to assess the influence of cardiovascular disease risk factors on levels of Lp(a) and to evaluate the effects of age, exercise, and estrogen on these levels. STUDY DESIGN: Two studies, a cross-sectional study of older men (n = 105) and women (n = 75) (mean age 76 years) and a prospective study of younger postmenopausal women (mean age 48 years), were carried out. Lp(a) and other lipoproteins were measured in the two studies and differences were sought by statistical analysis. RESULTS: In the cross-sectional study, serum Lp(a) was similar in men and women and was not influenced by age. Lp(a) levels in men and women were higher when there was more than one cardiovascular disease risk factor present (p less than 0.028). We could not demonstrate such a relationship with other lipid and lipoprotein measurements. In the prospective study exercise alone had no influence on Lp(a) levels. Oral estrogen decreased Lp(a) levels marginally (p = 0.08). The decrease in Lp(a) with oral estrogen was associated with increases in triglycerides (p less than 0.01) and very-low-density lipoprotein (p less than 0.06). CONCLUSIONS: These data confirm that elevated Lp(a) levels are an independent risk factor for cardiovascular disease. Lp(a) levels are primarily influenced by genetic factors and it appears estrogen may have a minor influence on its hepatic synthesis.
Aging↗
The gonadotropin-releasing hormone antagonist (Nal-Glu) acutely blocks the luteinizing hormone surge but allows for resumption of folliculogenesis in normal women.
The gonadotropin-releasing hormone antagonist offers several advantages over the use of the agonist and allows several physiologic questions to be addressed. In this study, we evaluated the ability of Nal-Glu to acutely inhibit the luteinizing hormone surge and prevent ovulation. We also assessed whether recovery of the follicle would be possible after several days of gonadotropin deprivation and estradiol decrement. Eight normal ovulatory women were randomized to control or Nal-Glu-treated cycles (50 micrograms/kg intramuscularly) for 3 to 4 days. Monitoring was carried out with daily vaginal ultrasonographic scans and serum estradiol levels and twice-daily serum luteinizing and follicle-stimulating hormone levels. Nal-Glu acutely inhibited the luteinizing hormone surge and ovulation, even when administered as late as the onset of the luteinizing hormone surge. Evidence was provided that spontaneous follicular rescue recurred in eight of 10 cycles after 3 to 4 days of Nal-Glu administration. Although an estradiol to follicular size dissociation occurred with Nal-Glu, subsequent ovulation occurred in 5.1 +/- 0.6 days after the last Nal-Glu dose. The decrement in estradiol after Nal-Glu administration correlated negatively with the days required for subsequent ovulation to occur (r = 0.77, p less than 0.05). The subsequent luteal phase also was normal in terms of length and progesterone levels. These data confirm the potency and efficacy of Nal-Glu in acutely inhibiting gonadotropins and extends our knowledge on the physiologic characteristics of the dominant follicle.
Adult↗
Serum erythropoietin levels after renal transplantation.
We measured serum erythropoietin levels serially in 31 renal-transplant recipients treated with cyclosporine, using the recently developed recombinant human erythropoietin-based radioimmunoassay. The mean (+/- SEM) serum erythropoietin concentration in these patients before transplantation (14 +/- 2 U per liter) was similar to that in normal subjects who did not have anemia. A transient postoperative 9-fold increase (range, 0- to 74-fold) in the serum erythropoietin levels was followed by a smaller (3-fold) and sustained (28 +/- 3 days) second elevation. The initial increase occurred in the absence of graft function and was not accompanied by an erythropoietic response, whereas the second increase was associated with graft recovery and the complete resolution of the anemia. Serum erythropoietin levels returned to normal as the hematocrit rose above 0.32. Thereafter, the hematocrit continued to rise toward normal, while the serum erythropoietin levels remained normal. The patients in whom erythrocytosis or iron-deficiency anemia developed had persistently elevated serum erythropoietin levels. We conclude that in patients who have undergone renal transplantation, slight increases in endogenous erythropoietin levels induce erythropoiesis to the same extent as do large doses of exogenous erythropoietin in patients with uremia. Moreover, once initiated, erythropoiesis in renal-transplant recipients may be sustained by normal serum erythropoietin levels. These results suggest that the restoration of renal function improves the erythropoietic response to erythropoietin.
Adult↗
Erythropoietin in renal transplant recipients: studies based on recombinant human erythropoietin radioimmunoassay.
In posttransplant patients, modest increases in endogenous EPO induce erythropoiesis similar to that observed in uremic patients who are given large doses of exogenous rHuEPO that generate vastly higher circulating EPO levels. Moreover, once it is initiated, erythropoiesis may be sustained by normal levels of EPO. These observations raise the possibility that the restoration of renal function may alter the EPO-erythropoiesis response pattern. It is also possible that the resolution of uremic anemia is dependent on factors in addition to the level of circulating EPO.
Biomarkers↗
Production of 3 alpha-androstanediol glucuronide in human genital skin.
3 alpha-Androstanediol glucuronide (3 alpha diol-G) is produced extrasplanchnically and is a good clinical marker of androgen action in peripheral tissues. However, the direct formation of androgen glucuronides in peripheral sites such as skin has not been determined in man. Genital skin from 21 premenopausal women and 8 men and foreskin from 6 neonates were incubated with either [14C]testosterone [14C]dihydrotestosterone (DHT) to determine the production of DHT glucuronide and 3 alpha diol-G in skin. After hydrolysis of incubation medium with glucuronidase, followed by extraction and sequential chromatography, constant 3H to 14C ratios of 3 alpha diol confirmed the production of DHT glucuronide and 3 alpha diol-g. The conversion of DHT to 3 alpha diol-G was higher than the conversion from testosterone (P less than 0.05), and conversion was higher in men than in women. These data provide evidence for the direct formation of C19 steroid glucuronides by human skin.
Adult↗
Phenytoin injection precautions.
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Drug Eruptions↗
Psychological stress and increases in urinary norepinephrine metabolites, platelet serotonin, and adrenal androgens in women with polycystic ovary syndrome.
Twenty-three women with polycystic ovary syndrome, 10 women with hypothalamic-pituitary dysfunction, and 50 control subjects were studied in an attempt to investigate the prevalence of psychological stress and its possible relationship to various hormonal parameters. Norepinephrine (NE) excretion, as reflected by urinary 3-methoxy-4-hydroxyphenylglycol (MHPG), and urinary 3-methoxy-4-hydroxymandelic acid (VMA), platelet serotonin, plasma adrenocorticotrophic hormone (ACTH), urinary free cortisol, serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), androstenedione (Adione), dehydroepiandrosterone (DHEA), its sulfate (DHEA-S), delta 5-androstenediol (delta 5-Adiol), testosterone (T), and unbound estradiol (E2) were measured. In addition, psychological stress was assessed by means of questionnaires modified from the Schedule of Recent Experiences, in which a Life Events Inventory was scored between 1 and 100. Women with polycystic ovary syndrome had significantly elevated levels of serum LH, LH:FSH ratios, unbound E2, Adione, DHEA, delta 5-Adiol, T, and DHEA-S (p less than 0.01). The number of Major Life Events (events scored on the questionnaire above 60) was significantly higher in women with polycystic ovary syndrome than in control women and women with hypothalamic-pituitary dysfunction (p less than 0.05). Urinary MHPG and platelet serotonin levels were also significantly higher in women with polycystic ovary syndrome (p less than 0.05), whereas VMA was normal. Levels of plasma ACTH and urinary free cortisol were similar in all groups. There was a significant positive correlation between MHPG and DHEA-S, MHPG and LH, and LH and T levels in women with polycystic ovary syndrome and those with hypothalamic-pituitary dysfunction (p less than 0.01). VMA also correlated with DHEA-S (p less than 0.05). In conclusion, psychological stress may be more prevalent in women with polycystic ovary syndrome and may be associated with elevated levels of MHPG and platelet serotonin. Because we have found that MHPG, but not VMA, correlated with LH, and because both MHPG and VMA correlated with DHEA-S, we hypothesize here that psychological stress and neurotransmitter levels may be linked to some of the hormonal derangements, including inappropriate gonadotropin secretion and elevated adrenal androgen levels in women with polycystic ovary syndrome.
Adolescent↗
Postoperative atelectasis: Intermittent positive pressure breathing, incentive spirometry, and face-mask positive end-expiratory pressure.
Postoperative atelectasis has been treated with inspiratory maneuvers in an attempt to increase functional residual capacity. We compared the effect of intermittent positive pressure breathing (IPPB), incentive spirometry, and 5-cm H2O positive end-expiratory pressure (PEEP) applied with a face mask on the transpulmonary pressure (PL) at the end of expiration of eight patients 24 to 34 hours after aortocoronary bypass graft insertion. Intermittent positive pressure breathing and PEEP increased expiratory PL during therapy. After IPPB, expiratory PL fell below control values and then returned toward, but did not reach, control values After PEEP was discontinued, expiratory PL returned to control values within the next 30 minutes. The results suggest that face-mask PEEP will increase functional residual capacity, that incentive spirometry has little or effect, and that IPPB may decrease lung volume after treatment.
Humans↗
Positive end-expiratory pressure (PEEP) and cerebrospinal fluid pressure during normal and elevated intracranial pressure in dogs.
The effect of up to 15 cm H2O positive end-expiratory pressure (PEEP) on cerebrospinal fluid pressure (Pcsf) was investigated in five anaesthetised, mechanically ventilated dogs during normal and then elevated (40-50 cm H2O) intracranial pressure (ICP). Stepwise elevations of PEEP in 5 cm H2O increments resulted in small rises in Pcsf at normal ICP and in significantly larger rises when ICP was elevated. The regression equations for the relationships between Pcsf and end-expiratory pressure (EEP) were as follows: Pcsf = 12.95 + 0.82 EEP for normal ICP, and Pcsf = 46.41 + 2.06 EEP for elevated ICP. Mean PaCO2 rose from 39.7 +/- 2.5 to 47.6 +/- 5.0 torr during normal ICP, and from 34.2 +/- 2.9 to 50.9 +/0- 5.3 torr at elevated ICP as PEEP was elevated to 15 cm H2O. We conclude that PEEP raised Pcsf, and that this increase is more severe under conditions of elevated ICP. The rise in Pcsf due to PEEP may be explained by either the rise in intrathoracic pressure or the rise in PaCO2, or both.
Animals↗
Neurologic depression after intrathecal morphine.
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Central Nervous System↗
Serum levels of DHEAS in gynecologic endocrinopathy and infertility.
Serum dehydroepiandrosterone sulfate (DHEAS) was measured in 32 infertility patients who were found to be ovulatory, in 37 women with oligomenorrhea, and in 52 hirsute patients under basal conditions. It was also measured in conjunction with adrenocorticotropic hormone (ACTH) stimulation and dexamethasone suppression in 10 of the hirsute women. Serum DHEAS levels were elevated in only 19% of the infertile women with regular ovulation, in 34% of the oligomenorrheic patients, and in 60% of the hirsute women. Of the C-19 steroids (androgens) measured in the 52 hirsute women, ie, total and unbound serum testosterone (T), androstenedione (A), and DHEAS, unbound serum T was most frequently elevated. Eighty-two percent of the hirsute women had either an elevated serum DHEAS level or an increased unbound T level, suggesting 1) that elevations in unbound serum T may be associated with or result from increased serum DHEAS levels and 2) that only a minority of women with so-called idiopathic hirsutism do not have demonstrable androgen excess. Three of 10 hirsute women with elevated serum DHEAS levels had an increased ACTH-induced rise in DHEAS. Dexamethasone given as a single daily dose of 0.5 mg at bedtime resulted in a marked decrease in serum DHEAS in all of the 10 hirsute patients tested within 2 weeks of therapy. Thus, serum DHEAS is a clinically useful indication of adrenal C-19 steroid secretion. When combined with clinical and other hormonal evaluations, its measurement adds an important dimension to the study of gynecologic endocrinology and infertility.
17-Ketosteroids↗
Dehydroepiandrosterone sulfate as an indicator of adrenal androgen function.
This study was undertaken to determine whether serum dehydroepiandrosterone sulfate (DHEA-S) assays could be used in lieu of urinary 17-ketosteroid (17-KS) determinations. To delineate normal values, serum DHEA-S levels were measured in 41 normal women (controls). These averaged 1.78 +/- 0.1 (SE) micrograms/ml and ranged from 0.3 to 2.8 micrograms/ml. Serum DHEA-S and urinary 17-KS and creatinine were measured in 71 patients with and without signs of androgen excess who were attending the Reproductive Endocrinology/Infertility Clinic. Serum DHEA-S levels did not correlate with body weight, surface area, or ponderal index, and were not elevated in obese women without androgen excess. Both normal and elevated serum DHEA-S concentrations correlated well with total urinary 17-KS when corrected for creatinine (P < .0005). In another group of 26 patients, the 2 urinary 17-KS fractions androsterone (A) and dehydroepiandrosterone (DHEA) correlated well with serum DHEA-S levels, but the third urinary 17-KS fraction, etiocholanolone (E), did not correlate. Eleven of the 26 patients who had elevated serum DHEA-S concentrations excreted increased amounts of urinary A and DHEA but not E. It is concluded that serum DHEA-S levels are much more conveniently measured than urinary 17-KS and should replace the latter because DHEA-S is a better indicator of adrenal "androgen" secretion.
Adrenal Glands↗
Adult body temperature and heated humidification of anesthetic gases during general anesthesia.
To determine the effects on body temperature of heating and humidifying inspired anesthetic gases to 37 C and 100% relative humidity, 42 men who had major surgical procedures under general anesthesia were studied. Group 1 (control) consisted of 10 patients who inspired gases from a standard semicircle absorber system with no added humidity. The mean nasopharyngeal temperature decreased significantly from 36.2 +/- 0.1 C to 34.9 +/- 0.2 C. Ten other patients, group 2, inspired gases that were heated and humidified. Mean nasopharyngeal temperature was maintained at 36.4 +/- 0.2 C with no significant changes throughout the study. One patient in this group became hypothermic, but only transiently. Ten patients, group 3, were allowed to become hypothermic before gases were heated and humidified. The mean nasopharyngeal temperature increased significantly from 34.7 +/- 0.2 C to 36.0 +/- 0.3 C during 4 hours of heated humidification. For groups 4 and 5, six patients each, gases were heated and humidified on alternate hours. The responses of the two groups demonstrated a causal relationship between the heating and humidifying of inspired gases and an increased mean nasopharyngeal temperature. It is concluded that heating and humidifying gases to 37 C and 100% relative humidity effectively maintains normothermia and rewarms hypothermic adults during general anesthesia.
Anesthesia, Inhalation↗
Serum ferritin level. Determinant of iron requirement in hemodialysis patients.
Seventeen patients without renal failure and 14 patients receiving long-term hemodialysis were studied. Serum and bone marrow ferritin determinations were made at the time of bone marrow aspiration. A good correlation was found between serum ferritin levels and bone marrow iron stores, as well as between bone marrow ferritin levels and iron stores. Serum ferritin determinations appear to give an accurate estimation of bone marrow iron stores, thereby providing a reliable guide for iron replacement therapy and reducing the need for repeated bone marrow aspirations. Serum ferritin levels of less than 105 ng/ml suggest decreased iron stores, and values greater than 120 ng/ml indicate adequate or increased iron stores. Preliminary data also suggest that bone marrow ferritin determinations may be useful in quantitating bone marrow iron stores.
Anemia, Hypochromic↗
Binding of N-substituted anthracenecarboxamides to double-stranded DNA: an electronic spectral study.
The electronic absorption and fluorescence spectra of two isomeric anthracenecarboxamides substituted with quaternary alkyl ammonium groups were studied as a function of solvent polarity, solvent rigidity, and state of protonation. These relatively simple environmental perturbations of the electronic spectra were employed to interpret spectral shifts caused by complexation with the bases or base pairs of DNA. The exocyclic side chains of the compounds studied have some freedom of movement when the spectroscopic probes are bound to double-stranded DNA.
Anthracenes↗
Central-nervous-system toxicity of local anesthetic mixtures in monkeys.
The central-nervous-system toxicities of local anesthetic mixtures consisting of lidocaine and etidocaine or lidocaine and tetracaine, administered intravenously to four healthy, non-medicated rhesus monkeys, were evaluated. Toxicities were compared by determining seizure dosages for each drug alone and then in a lidocaine-etidocaine-tetracaine mixture. Arterial plasma levels of lidocaine and etidocaine at which electrical seizure activity occurred also were measured when the drugs were administered alone and in combination. The seizure dosages and arterial plasma levels for the drug mixtures studied were equal to the sums of the dosages and thresholds for individual constituents of the mixtures. Under the conditions of this investigation local anesthetic toxicity was additive. (Key words: Anesthetics, local, lidocaine; Anesthetics, local, etidocaine; Anesthetics, local, tetracaine; Brain, seizure thresholds; Toxicity, convulsions.)
Acid-Base Equilibrium↗