Styles of liaison psychiatry: discussion paper.
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Hospitals, General↗
Biomedical subjects
A White
Publications and source records attributed to A White.
Vasopressin mediates alpha 1-adrenergic stimulation of adrenocorticotropin secretion.
In conscious rats bearing venous and cerebroventricular cannulae, central administration of the alpha 1-adrenergic agonist methoxamine stimulated the secretion of ACTH, and the effect was reduced by the alpha 1-antagonist prazosin. Methoxamine was more potent in stimulating ACTH secretion when injected icv than peripherally, suggesting that the stimulant alpha 1-adrenoceptors are located in the brain rather than in the periphery. In order to investigate the relative roles of hypothalamic CRF-41 and vasopressin as mediators of the stimulant effects of alpha 1-adrenoceptors on ACTH secretion, we examined the effects of equipotent doses of antagonists to CRF-41 and vasopressin on the ACTH responses to methoxamine. The effect of methoxamine was reduced by the vasopressin antagonist dPTyr(Me) arginine vasopressin but not by the CRF-41 antagonist alpha-helical CRF-9-41, suggesting that vasopressin is more important than CRF-41 in mediating the effects of alpha 1-adrenoceptors on ACTH secretion. However, the combination of the two antagonists caused a reduction in the ACTH response to methoxamine that was greater than that of the vasopressin antagonist alone. This suggested that CRF-41 plays some role in this response, possibly by enhancing the activity of vasopressin in a synergistic manner. These two hypothalamic peptides seem to account for most of the ACTH releasing activity of alpha 1 adrenoceptor activation.
Adrenocorticotropic Hormone↗
Brattleboro rats have deficient adrenocorticotropin responses to activation of central alpha 1-adrenoceptors.
This experiment was designed to test further the hypothesis that vasopressin is the major mediator of the ACTH response to activation of central alpha 1-adrenoceptors in the rat. The alpha 1-adrenergic agonist methoxamine was given intracerebro-ventricularly to conscious vasopressin-deficient (homozygous Brattleboro) and normal rats bearing venous and intracerebro-ventricular cannulae. Methoxamine stimulated the secretion of ACTH in the normal, but not in the vasopressin-deficient, rats. The data confirm that vasopressin, rather than CRH-41 or oxytocin, is the major hypothalamic peptide that mediates the effects of central alpha 1-adrenoceptors on the pituitary corticotrophs.
Adrenocorticotropic Hormone↗
Defective glucocorticoid regulation of proopiomelanocortin gene expression and peptide secretion in a small cell lung cancer cell line.
A human small cell lung cancer cell line (COR L103) that actively expresses the proopiomelanocortin (POMC) gene has been used as a model of extrapituitary ACTH-secreting tumors to investigate the phenomenon of resistence of ACTH production to glucocorticoids. After both short term (24 h) and long term (10 days) exposure to hydrocortisone at concentrations of 500 and 1000 nM, the accumulation of intracellular POMC mRNA, ACTH, and ACTH precursor peptides in the culture medium was not suppressed. These finding contrast with those in the pituitary corticotroph cell line AtT20, in which POMC mRNA, ACTH, and ACTH precursors were suppressed under the same conditions. Two other genes that are regulated by glucocorticoids in other cell types, the tyrosine amino transferase gene and the glucocorticoid receptor gene, were expressed in COR L103 cells. However, neither gene appeared to be regulated by hydrocortisone in this small cell lung cancer cell line. Further studies demonstrated that glucocorticoid receptor binding could be detected in the nucleus and cytoplasm, with a Kd of 5 X 10(-9) M. It is concluded that nonsuppression of POMC by glucocorticoids is probably part of a more global defect of glucocorticoid signaling in these cells, but that this defect lies distal to steroid binding in the nucleus.
Adrenocorticotropic Hormone↗
Activation of pituitary-adrenal function in fetal sheep by corticotrophin-releasing factor and arginine vasopressin.
In sheep, birth is preceded by an increase in fetal plasma concentrations of ACTH and cortisol. Activation of the fetal pituitary-adrenal axis is pivotal to the onset of parturition in this species and may be regulated, at least in part, by corticotrophin-releasing factor (CRF). Pulsed administration of CRF has been shown to activate the fetal pituitary-adrenal axis in immature fetal sheep. However, pituitary ACTH responsiveness declined after continued administration of CRF, as a result of increasing negative feedback effects of increased concentrations of endogenous cortisol. To test the hypothesis that arginine vasopressin (AVP) is required, in addition to CRF, to produce the necessary trophic stimulus to the pituitary-adrenal axis, we administered saline, CRF (1 microgram), AVP (200 ng) or CRF plus AVP as pulses every 4 h for 7 days to fetal sheep beginning at days 117-120 of pregnancy (term = 145 days). Pituitary-adrenal responses were assessed by measuring plasma concentrations of immunoreactive (ir) ACTH and cortisol in response to one of the pulses on each of the 7 days of treatment. On day 1, CRF and AVP significantly increased plasma concentrations of ir-ACTH and there was a synergistic interaction when the two peptides were given together (P less than 0.05). However, as pulsed treatment continued there was a decline in the pituitary ir-ACTH response to all treatments (P less than 0.05). This decline in pituitary response occurred over a much longer period of time when CRF and AVP were given together when compared with the two peptides given separately.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenocorticotropic Hormone↗
Comparison of ACTH and ACTH precursor peptides secreted by human pituitary and lung tumour cells in vitro.
The molecular forms of ACTH secreted by established human small cell lung cancer (SCLC) cells and primary cultures derived from a bronchial carcinoid tumour, a pituitary adenoma and hyperplastic pituitary tissue have been characterized by Sephadex G-75 chromatography and quantified with two novel immunoradiometric assays for ACTH and ACTH precursor peptides. Pro-opiomelanocortin (POMC; Mr 31,000) and pro-ACTH (Mr 22,000) were secreted by all cell types. No smaller peptides were identified in the culture media from SCLC and bronchial carcinoid cells, implying a deficiency in the enzymes and/or intracellular organelles required for extensive POMC processing. A more heterogeneous profile of ACTH-containing peptides was produced by cells of pituitary origin, indicating more extensive proteolytic processing of POMC. However, the major peptide secreted by cells from a large aggressive pituitary adenoma was unprocessed POMC (Mr 31,000). These results suggest that both lung and pituitary cells in vitro retain their in-vivo pattern of POMC processing and provide valuable models in which to study the regulation of ACTH synthesis and secretion.
Adenoma↗
Anorexia nervosa in the elderly: a case report and review of the literature.
Anorexia nervosa is a rare disorder in the elderly but should be thought of in the differential diagnosis of extreme weight loss, especially if there are accompanying psychological features and normal baseline investigations. Psychiatric opinion should be obtained and treatment, although of unproven value, considered, since improvement may increase mobility and reduce morbidity and mortality.
Aged↗
[Financing research in Chile in biotechnology and other areas related to the productive sector].
This study describes the financial support for research in Chile in different areas related to the productive sector including biotechnology. Four different sources which help research in the country through competitive research grants were analysed. These include: FONDECYT (National Fund for Research and Technology), Fondo de Desarrollo Productivo de CORFO (Fund for Productive Development), Fondo de Investigaciones Agropecuarias (Fund for Research in Agriculture and Livestock) and the IV Program for Technical Cooperation between the Chilean Government and UNDP. Biotechnology appears as one of the areas related to the productive sector having an important number of projects approved with a substantial financial support. Based in a survey, recommendations are made to improve the relationship between the productive and academic sector in biotechnology and other areas.
Biotechnology↗
Efficacy and safety of ofloxacin in the treatment of nongonococcal sexually transmitted disease.
This study compared doxycycline with ofloxacin in the treatment of nongonococcal urethritis in men and mucopurulent cervicitis in women and compared both drugs in the treatment of infections due to Chlamydia trachomatis in both men and women. Informed consent was obtained from all subjects. Eighteen men with nongonococcal urethritis and 12 with previously positive chlamydial cultures were randomly treated with doxycycline or ofloxacin. Eleven women with mucopurulent cervicitis, 14 with a previous positive untreated chlamydial culture, and nine having sexual contacts with men known to have chlamydial urethritis also were randomly treated. Culture specimens for chlamydia were obtained before treatment, five to nine days after therapy (return visit 1), and 21 to 28 days after therapy (return visit 2). Cultures for Ureaplasma urealyticum were obtained only in men. There were no significant differences in results in patients treated with doxycycline or ofloxacin. All but three of 20 men with symptoms were symptom-free on return visit 1 and all were symptom-free on return visit 2. Thirteen women with mucopurulent cervicitis had all resolved at visit 1, although signs of cervicitis reappeared at the second visit in two patients treated with doxycycline and one treated with ofloxacin. All patients with positive chlamydial cultures had negative cultures at the first return visit. One patient treated with doxycycline was positive at the second return visit. Laboratory and clinical abnormalities were mild and did not prevent completion of therapy. These data, together with previous published and unpublished data, indicate that ofloxacin is as effective as doxycycline in the treatment of chlamydial infections. The study also demonstrated that ofloxacin and doxycycline were equally effective in the treatment of nongonococcal urethritis in men and mucopurulent cervicitis in women.
Chlamydia Infections↗
A prospective clinical audit of methadone maintenance therapy at the Royal Newcastle Hospital.
In a prospective study of 63 admissions to a methadone maintenance programme in a public hospital, 13 admissions were for less than two weeks. Of the remaining 50 such admissions, 35 admissions were terminated because of absenteeism, drug abuse, violence or drug-dealing. Twelve patients did not take intravenously administered drugs during the time that they were receiving methadone, but in 25 of the 50 admissions that lasted for more than two weeks, such drugs were abused at least fortnightly. Eight patients achieved a stable state without drugs that lasted at least three months. No improvements were note in patients' social situations, relationships, health or criminal activity, but compliant patients did improve their employment status. A significant minority of patients has benefited from methadone maintenance therapy, but most patients have continued their drug abuse and drug-related life-styles.
Adolescent↗
The proposal to make heroin available legally to intravenous drug abusers.
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Australia↗
Malignant fibrous histiocytoma of lung.
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Histiocytoma, Benign Fibrous↗
Small cell lung cancer cell lines secrete predominantly ACTH precursor peptides not ACTH.
A panel of 18 well characterised human small cell lung cancer (SCLC) cell lines was assessed for the production of adrenocorticotrophin (ACTH) and its precursor peptides, pro-opiomelanocortin (POMC) and pro-ACTH. These precursor peptides were measured directly using a novel two-site immunoradiometric assay (IRMA) based on monoclonal antibodies, in conjunction with a similar IRMA for ACTH 1-39. Significant concentrations of ACTH precursors were secreted by 10 of the 18 cell lines (56%). The low levels of ACTH immunoreactivity detected in seven cell lines could be accounted for by the known cross-reactivity of precursors in the ACTH IRMA. This suggests there is little, if any, processing of ACTH precursors to ACTH. Cell pellet extracts contained undetectable or low levels of ACTH precursors and ACTH, indicating that these peptides are not stored intracellularly. During the growth of the SCLC cells in vitro ACTH precursors accumulated progressively in the culture medium. Thus the combination of a direct assay for the ACTH precursors and the panel of SCLC cell lines provides a valuable in vitro model for the expression of POMC in human tumours.
Adrenocorticotropic Hormone↗
A comparison of the thermogenic effects of CRF, sauvagine and urotensin I in the rat.
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Adipose Tissue↗
Occult infections causing persistent low-back pain.
Occult infections caused by indolent organisms may produce persistent back pain that may be difficult to diagnose. The usual findings considered indicative of spinal infection are not reliable in these cases. The authors describe nine patients who presented with occult infections of the lumbar spine. Two of the nine had no antecedent lumbar surgeries nor open wounds. The predominant organisms were diptheroids and coagulase-negative staphylococci. The diagnosis was established by the clinical course, pathologic tissue changes at surgery, cultures, and response to antibiotic therapy. Normal Westergren sedimentation rates were noted in seven of nine patients, and normal white blood cell counts in six of nine patients. With the exception of two positive computed tomography (CT) scans, one positive gallium scan, and one positive magnetic resonance imaging (MRI) scan, all remaining imaging studies were negative for infection. In many cases, the infection neither was limited to nor involved the disc space.
Abscess↗
The pituitary-adrenal response to CRF-41 is unaltered by intravenous somatostatin in normal subjects.
We have previously reported that the hypothalamo-pituitary-adrenal response to insulin-induced hypoglycaemia is normal while the cortisol release to pituitary stimulation by corticotrophin releasing factor (CRF-41) is reduced in obesity. Impaired growth hormone (GH) secretion is also found in obesity which may result from altered central levels of somatostatin (SMS). We have investigated, by giving a simultaneous infusion of SMS to six volunteer normal weight men during a CRF test, whether it is possible for SMS to modify pituitary-adrenal function. Each subject received intravenous CRF-41 (0.5 micrograms/kg) on two occasions during an infusion of isotonic saline or SMS (4 micrograms/min) in a randomized double-blind study. Plasma GH, cortisol, ACTH and SMS were measured. Three subjects demonstrated GH peaks during saline infusion but no peaks were seen in any subject during SMS infusion. No significant difference was found between peak cortisol responses during saline or SMS infusion (SMS cortisol 443 +/- 61 nmol/l, saline cortisol 485 +/- 52 nmol/l); neither was there any difference in the ACTH responses. We conclude that SMS does not alter the pituitary response to CRF in normal weight men and is thus less likely to be responsible for the altered pituitary-adrenal function seen in obesity. Further studies of alternative mechanisms are required to explain the cause of this abnormality.
Adrenocorticotropic Hormone↗
Comparison of the ACTH and cortisol responses to provocative testing with glucagon and insulin hypoglycaemia in normal subjects.
The glucagon stimulation test (GST) is often used to assess pituitary ACTH reserve, particularly when other tests are contra-indicated. In a preliminary investigation, in patients with pituitary disease, we failed to demonstrate the ACTH dependence of the cortisol response. We have therefore compared the ACTH, cortisol and glucose responses to glucagon (1 mg s.c.), insulin (0.2 U/kg i.v., ITT) and placebo in six healthy male volunteers, sampling every 10 min for 6 h. During the GST, mean +/- SD serum cortisol rose from 256 +/- 80 nmol/l to a peak of 481 +/- 164 nmol/l (range 289-717 nmol/l, P less than 0.01) in comparison with 280 +/- 81 nmol/l to 602 +/- 110 nmol/l (range 493-742 nmol/l) during the ITT (P less than 0.002). The mean peak cortisol levels achieved in the two tests did not differ significantly. In the GST, plasma ACTH rose from a mean basal value of 10.9 +/- 16.6 ng/l to a mean peak level of 123 +/- 76 ng/l (P less than 0.02) (ACTH ng/l x 0.225 = pmol/l). The corresponding values in the ITT were 7.1 +/- 16.2 ng/l and 263 +/- 91 ng/l (P less than 0.001). The mean peak ACTH level was significantly greater during the ITT (P less than 0.05). Thus the cortisol response was ACTH dependent in both the GST and the ITT in normal subjects. Furthermore, the ACTH response was of sufficient duration to be detected by the usual procedure of sampling every 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenocorticotropic Hormone↗
The effect of ovine corticotrophin-releasing factor on the hormonal response to insulin-induced hypoglycaemia.
In order to investigate the role of hypothalamic corticotrophin-releasing factor (CRF41) in the mediation of the pituitary ACTH response to hypoglycaemia, eight normal adult males were studied on four occasions. Commencing at 0830 h after an overnight fast, each received, in double-blind, random order, intravenous boluses of: A, normal saline control; B, soluble insulin 0.15U/kg; C, ovine CRF41 (oCRF41) 100 micrograms; D, soluble insulin 0.15U/kg followed immediately by oCRF41 100 micrograms. Adequate hypoglycaemia (blood glucose less than 2.2 mmol/l) was achieved in each subject when insulin was given alone or with oCRF41, and there was no difference in the glucose nadir between the 2 days. Peak plasma ACTH was significantly higher after insulin plus oCRF41 than after insulin alone (P less than 0.05) or oCRF41 alone (P less than 0.01) and this enhancement of ACTH release was most marked in the first phase of the response at 30 min (P less than 0.001, b vs d). There was no difference in the peak serum cortisol response whether oCRF41 and insulin were given alone or together and although the area under the cortisol curve was greater after insulin plus oCRF41, this difference was explicable simply on the basis of the earlier onset of the cortisol response to oCRF41. There were no differences in the serum GH responses to hypoglycaemia on the 2 days.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenocorticotropic Hormone↗