CNV and dopamine receptor reactivity: correlations with the apomorphine test.
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Adult↗
Biomedical subjects
J J Legros
Publications and source records attributed to J J Legros.
Adipsic hypernatremia in a patient with pseudotumor cerebri and the primary empty sella syndrome.
Adipsic hypernatremia, a rare disorder, usually secondary to a hypothalamic lesion, is caused by the combination of partial central diabetes insipidus with hypo- or adipsia. We studied a patient who presented with a global hypothalamic dysfunction including adipsic hypernatremia. An extensive work-up disclosed the presence of pseudotumor cerebri and an empty sella turcica. Although endocrine abnormalities including true diabetes insipidus have been reported in conjunction with pseudotumor cerebri or an empty sella, no patient described presented such a global hypothalamic dysfunction or adipsic hypernatremia. The increased intracranial pressure is postulated to be the responsible mechanism for both the empty sella and the hypothalamic dysfunction.
Adult↗
Syndrome of inappropriate secretion of antidiuretic hormone after severe head injury.
This study is based on 109 patients with severe head injury who had a Glasgow coma score equal to or less than 7 and a Liège coma score equal to or less than 12 in the first 24 hours. The syndrome of inappropriate secretion of antidiuretic hormone seems to us to be a frequent complication of severe craniocerebral trauma. It has been discovered in 33% of our patients. On the other hand, diabetes insipidus was rarely diagnosed (2.8%). We propose, in cranial trauma, to subdivide the syndrome of inappropriate secretion of antidiuretic hormone into two clinical forms: an early syndrome (5%) that becomes apparent towards the second day and is significantly associated with lesions at the base of the skull; and a delayed syndrome that occurs at the end of the first week and is related to different factors inherent in intensive care procedures. Surgical intervention, in the case of acute craniocerebral trauma, does not result in a higher frequency of inappropriate secretion of antidiuretic hormone.
Adolescent↗
Release of human neurophysin I during insulin-induced hypoglycemia in depressed patients is abolished after recovery with clomipramine treatment.
Release of human neurophysin I (hNp I) and neurophysin II (hNp II) during insulin-induced hypoglycemia was studied in 10 unipolar depressed women before and after 4-5 weeks of standard antidepressant drug treatment with daily intravenous infusions of clomipramine. Before treatment, a significant increase of hNp I but not of hNp II serum levels in response to hypoglycemia was observed. At retest during clomipramine administration, a marked clinical amelioration occurred in all patients as determined with the Hamilton Rating Scale for Depression; the hNp I response to insulin was abolished, but no effect on hNp II concentration could be demonstrated. No correlation was found between the degree of the depression score decrease and the amplitude of the inhibition of hNp I release or serum levels of clomipramine or its metabolite, desmethylclomipramine. The meaning of this difference in reactivity of the neurohypophyseal system in the course of depressive illness, based on the pharmacological and biochemical profiles of clomipramine action, is discussed.
Blood Glucose↗
Diagnostic performance of the thirty-four hour dexamethasone suppression test.
The performance of the dexamethasone suppression test (DST) in the diagnostic confirmation of endogenous depression was compared according to two times of blood collection--1600 hr on day 2 (usual sample) and 0800 hr on day 3 (34 hr after dexamethasone intake)--in 14 endogenous depressives and in a control group of 17 psychiatric inpatients with other diagnoses. For the day 2 (1600 hr) sample, a 5 micrograms/dl cortisol concentration represented the best cut-off score, with sensitivity of 57% specificity of 88%, and diagnostic confidence of 80%. For the day 3 (0800 hr) sample, the best cut-off score was 20 micrograms/dl, with the same sensitivity (57%) but there was a decrease of both specificity (to 76%) and diagnostic confidence (to 67%). The mean cortisol levels were much higher on day 3 than on day 2, suggesting that the inhibitory activity of dexamethasone was no longer present.
Adult↗
[Value of the sleep EEG as a biological marker of depressive states. Comparison with 3 neuroendocrine tests].
In a sample of 12 endogenous depressive inpatients (8 primary and 4 secondary depressives), we compared the diagnostic usefulness of REM latency (recorded during at least 4 consecutive nights) with 3 neuroendocrine tests: dexamethasone suppression test and GH response after clonidine (a alpha-adrenergic agonist) and apomorphine (a dopaminergic agonist) challenges. Shortened REM latency (less than 50 min during at least 1 night) was present in 67% of depressives. However, REM latency presented a clear night to night intra-patient variability that makes it necessary to record at least 3 consecutive nights for the best sensitivity. Non-suppression after dexamethasone was present in 50% of depressives, blunted GH response after clonidine, in 75% and blunted response after apomorphine, in 42%. A total of 92% of patients exhibited at least one abnormal biological parameter (100% of primary and 75% of secondary depressives); 67% of patients exhibited at least two disturbed parameters and these patients constituted the whole primary depressive group (100%). These results show that these 4 potential biological markers of depression are not necessarily distributed in the same population. This suggests the potential usefulness of their concurrent use for improved accuracy of diagnosis.
Adult↗
High molecular weight vasopressin: detection of a large amount in the plasma of a patient.
Using a sensitive and specific radioimmunoassay for arginine-vasopressin, we have searched for the presence of high molecular weight (HMW) vasopressin in the plasma of a patient with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and an oat cell carcinoma of the lung. After incubation in 8 mol/l urea, one millilitre of the plasma from this patient was fractionated on a Sephadex G-50 column and the immunoreactive vasopressin content was evaluated before and after trypsin treatment of the eluted fractions. A wide peak of apparent mol. wt. 2500-6000 daltons was revealed only after tryptic digestion of each fraction. This peak contained the equivalent of 1900 pg of vasopressin. A tryptic digest of this peak, rechromatographed on Sephadex G-25, gave two small peptides the major one eluting at a position identical to vasopressin. These results demonstrate the presence of a large amount of HMW vasopressin in the plasma of a patient with SIADH and oat cell carcinoma of the lung.
Aged↗
Release of immunoreactive oxytocin and neurophysin I by cultured luteinizing bovine granulosa cells.
We investigated the production of oxytocin (OT) and oxytocin-neurophysin (bNpI) by bovine granulosa cells cultured in presence of 10% foetal calf serum, a condition known to induce spontaneous luteinization of these cells. The production of immunoreactive OT was significantly higher in the cultures of granulosa cells harvested from large follicles than in those derived from small follicles. Chromatography on Sephadex G-25 showed similar elution sites of ovarian and synthetic OT, while high performance liquid chromatography revealed two peaks of OT-immunoreactivity, one of which (+/- 65% of the total immunoreactivity) coincided with synthetic OT. In another experiment, we could observe a gradual increase of OT, bNp I and progesterone production by granulosa cells derived from large follicles, in relation with the incubation time. The mean molar ratio OT: bNp I was 2.2 +/- 0.5 (SEM), and we found a significant positive correlation between the production of OT and bNp I (r = 0.77; P less than 0.01) and between the production of OT and progesterone (r = 0.80; P less than 0.01). Furthermore, the cellular OT and bNp I content of large follicles-derived granulosa cells before culture was 4-5 times lower than the total amount of OT and bNp I produced during a 72-h incubation, suggesting an active synthesis of these peptides. These data show that bovine granulosa cells are able to produce OT and bNp I, probably by an active biosynthesis as observed in the hypothalamo-neurohypophysial system and that the granulosa productions of OT, bNp I and progesterone are closely related.
Animals↗
Regulation of vasopressin secretion in a patient with chronic hypernatraemia.
A patient with the chronic hypernatraemia syndrome is described. Using a sensitive and specific radioimmunoassay, the plasma arginine-vasopressin (AVP) level was measured under various conditions. With an unrestricted diet, the plasma AVP level was inappropriately low for the degree of plasma hyperosmolality (0.9 pmol/l and 302 mOsm/kg, respectively). After chronic water loading, plasma osmolality was 271 mOsm/kg, plasma AVP level 1.5 pmol/l, and the urine remained hypertonic with respect to the plasma. During hypertonic saline infusion, plasma osmolality increased from 271 to 294 mOsm/kg without a concomitant increase in the plasma AVP concentration. After sc injection of apomorphine and after haemodynamic stimulation, the plasma AVP concentration increased from 0.8 to 36 pmol/l and from 1.2 to 6.3 pmol/l, respectively. These data demonstrate a selective deficiency in the osmoregulation of the AVP secretion. The observed neuroendocrine abnormalities may be linked to a congenital malformation of the brain.
Adult↗
Evidence for the secretion of immunoreactive neurophysin I in addition to oxytocin from the ovary in cattle.
In Exp. I, blood samples were collected simultaneously from the posterior vena cava and jugular vein or aorta from 7 heifers every 5-20 min for 2-5 h. Concomitant pulsatile secretion of oxytocin and immunoreactive neurophysin I was detected in the vena cava, but not in the jugular vein or aorta. Concentrations of oxytocin and immunoreactive neurophysin increased earlier and were higher in the vena cava than in the jugular vein or aorta after the injection of a luteolytic dose of prostaglandin F-2 alpha analogue during the mid-luteal phase of the oestrous cycle, demonstrating its ovarian but not pituitary origin. In Exp. II, blood samples were collected from the jugular vein every 12 h during 1 week after oestrus. Follicular growth had been stimulated during the preceding oestrous cycle with PMSG (10 heifers and cows) or with FSH (5 animals); 6 heifers served as controls. There was a high correlation between the number of follicles or CL and the increase in oxytocin and immunoreactive neurophysin I. Although PMSG had a greater luteotrophic effect than did FSH on progesterone secretion, a similar stimulation of oxytocin and immunoreactive neurophysin I was not observed. It is concluded that immunoreactive neurophysin I and oxytocin are secreted from the ovary in concentrations dependent upon the number of corpora lutea (and of follicles) present. During the mid-luteal period the secretion occurs in a concomitant pulsatile fashion.
Animals↗
[Effect of physical training by swimming on the arterial pressure, plasma and hypothalamo-post-hypophyseal vasopressin in genetically hypertensive rats of the Lyon strain].
The effect of a 5-week swimming training on systolic blood pressure (PAS) and vasopressin (AVP) and Neurophysins (NpT) concentration in the blood and content in the pituitary and the hypothalamus was studied in Lyon genetically hypertensive rats [LH] and in their controls: the normotensive [LN] and low blood pressure [LL] rats belonging to the 28th generation. Nine female rats of each group were trained 5 days a week for 5 weeks, starting with 2 h a day, with a 15 min increase every day, up to 6 h a day. The PAS was measured using an indirect plethysmographic technique one time a week during the whole training session. At the end of the training, the rats were decapitated. AVP and NpT were measured in blood, pituitary and hypothalamus, by radioimmunoassay (RIA). Hematocrit as well as plasma Na+, K+, protein and osmotic content were also measured. Results show that the training did not affect any of the studied parameters: mainly, there was no decrease in PAS or plasma AVP level in the hypertensive rats compared to the normotensive ones. The only difference was a lower AVP content in the pituitary of LH rats compared to LN (p less than 0.01), which is difficult to interpret. Our results shed doubt on the efficiency of a swimming training on the evolution of hypertension in the Lyon rat model.
Animals↗
Neurophysin heterogeneity. Difference between newly formed and aged neurosecretory granules.
Neurosecretory granules from bovine neurohypophyses were isolated on iso-osmotic gradients. The content of the granules was analyzed by analytical and two-dimensional gel electrophoreses. The distributions in the gels of vasopressin precursor and neurophysins were detected by radioimmunoassays. Analytical gel electrophoresis of the content of a crude granule preparation showed the presence of different populations of neurophysin molecules. Further analysis demonstrated that vasopressin-neurophysin and oxytocin-neurophysin can be subdivided into molecules with different pI values. Whereas newly formed granules showed two main spots of neurophysin with pI of 5.0 and 5.6, aged granules contain in addition to these different populations of neurophysin-like material, some of which had a basic pI. Vasopressin precursor activity was detected in spots containing proteins with acidic pI and Mr approximately 18,000 and also in proteins of Mr = 8,000-10,000 migrating in the basic region of the gel. The results suggest that in the neural lobe there is an aging process which gives rise to several subpopulations of neurophysins. The different forms of vasopressin-associated bovine neurophysin and oxytocin-associated bovine neurophysin are only found in the granules which are not required for release.
Animals↗
Pergolide for pituitary tumors secreting prolactin or growth hormone.
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Acromegaly↗
Cerebrospinal fluid neurophysins in affective illness and in schizophrenia.
We studied the concentration of neurophysin I (hNPI) and II (hNPII), the hypothalamo-pituitary carriers of vasopressin and oxytocin, in CSF of depressed and schizophrenic patients and age matched controls. Mean hNPI values were lower and mean hNPII values greater in schizophrenics than in controls. Lower hNPI values were observed in unipolar patients than in controls. In bipolar patients however, higher hNPI values were present. Significantly higher hNPII values were observed in bipolar patients than in controls; no difference was present between unipolars and controls. A positive correlation was observed with age in controls and bipolars for hNPII. These data emphasize the interest of studying the neurohypophysal function in affective illness and in schizophrenia.
Adult↗
Simultaneous radioimmunoassay for plasma arginine-vasopressin and oxytocin using DEAE Sephadex A 25 extraction.
A sensitive and specific radioimmunoassay method for simultaneous measurement of plasma arginine vasopressin (AVP) and oxytocin (OT) has been developed utilizing an extraction technique on DEAE Sephadex A25. This procedure resulted in mean recoveries of 70.7% (AVP) and 65.4% (OT) in the peptide range of 5 to 100 pg/4 ml. The sensitivity of the assay is 0.5 pg/tube for AVP and 2 pg/tube for OT. The lower limit of detection for plasma extracts was 1.2 pg AVP/ml and 5 pg OT/ml plasma. Employing this method in normal human non smokers and ad libitum fluid the basal levels (mean +/- SE) of plasma AVP are 3.5 +/- 0.2 pg/ml in males and 4.6 +/- 0.4 pg/ml in females and the basal concentrations of plasma OT are 5.1 +/- 0.3 pg/ml in males and 5.4 +/- 0.3 pg/ml in females. Dehydration and water loading produced significant changes in plasma AVP and OT concentrations and a significant correlation exists between plasma AVP and plasma (r = 0.96, p less than 0.001) and urinary (r = 0.84, p less than 0.01) osmolality, but not between plasma OT concentrations and plasma (r = 0.11, NS) and urinary (r = 0.27, NS) osmolality. These results suggest that a wide range of physiological and pathophysiological changes in plasma AVP and OT can be simultaneously measured by the extraction procedure and the radioimmunoassay described.
Adult↗
Concurrent use of REM latency, dexamethasone suppression, clonidine, and apomorphine tests as biological markers of endogenous depression: a pilot study.
In a sample of 12 major depressive inpatients, endogenous subtype (8 primary and 4 secondary) defined by Research Diagnostic Criteria, we compared the sensitivity of four potential biological markers: latency of rapid eye movement (REM) sleep (recorded during at least 4 consecutive nights), dexamethasone suppression, and the clonidine and apomorphine tests. Shortened REM latency (less than 50 minutes during at least 1 night) identified 67% of depressives (87% of primary and 25% of secondary); nonsuppression after dexamethasone identified 50% of depressives (62% of primary and 25% of secondary); blunted growth hormone (GH) response after clonidine identified 75% of depressives (100% of primary and 25% of secondary); and blunted GH response after apomorphine identified 42% of depressives (62% of primary and 0% of secondary). Ninety-two percent of patients were correctly identified by at least one biological marker (100% of primary and 75% of secondary depressives). Of 67% of patients positive on at least two biological markers, all were primary depressives (100%). These four biological markers do not necessarily identify the same population, suggesting that their concurrent use may yield the highest level of diagnostic sensitivity.
Adult↗
Use of saliva cortisol in the dexamethasone suppression test.
In a sample of 26 inpatients (15 primary endogenous depressives and a heterogeneous comparison group of 11 psychiatric patients), results of the dexamethasone suppression test (DST) for endogenous depression were compared when cortisol was measured in plasma (total and free) and in saliva. Results showed a close linear relationship among plasma total and free cortisol, plasma total cortisol, and saliva cortisol, and between free plasma and saliva cortisol. A saliva cortisol cutoff point of 70 ng/dl achieved the same sensitivity (67%), specificity (91%), and diagnostic confidence (91%) as the best cutoff scores of plasma total cortisol (5 micrograms/dl) and plasma free cortisol (0.15 microgram/dl). These results suggest that saliva cortisol, which directly reflects the biologically active fraction of cortisol, can be used as a reliable and more practical index in the DST, especially in outpatients.
Adolescent↗
Dose-response relationship between plasma oxytocin and cortisol and adrenocorticotropin concentrations during oxytocin infusion in normal men.
We previously demonstrated that acute injection of a pharmacological dose of oxytocin (2 IU) in humans decreased the concentrations of ACTH and cortisol, a neuroendocrine action opposite that of vasopressin. In the present work the effect of continuous infusion of lower doses of oxytocin was tested. Plasma oxytocin was also measured using an oxytocin RIA to study the dose-response relation. Infusion of oxytocin (8 mIU/min for 30 min) resulted in a plasma oxytocin level of 9.9 +/- 1.4 (+/- SD) muIU/ml and induced a decrease in the plasma concentration of ACTH in three of four normal subjects. Infusion of oxytocin at the rate of 16 mIU/ml for 30 min resulted in plasma oxytocin level of 17.7 +/- 1.6 muIU/ml and decreases in plasma ACTH and cortisol concentrations in all six subjects tested. Increasing the oxytocin dose from 32 to 64 and 128 mIU/min for three additional 30-min periods induced more pronounced decreases in plasma ACTH and cortisol. In each subject, there was a highly significant inverse relationship between plasma oxytocin, and ACTH and cortisol (r = -0.85 to -0.99). During saline infusion, a significant inverse relationship with a 10-min lag period between plasma oxytocin and ACTH (r = -0.55) was found in only one of six subjects. These data demonstrate that infusion of exogenous oxytocin leading to plasma levels approximately 10 times higher than normal induced consistent decreases in corticotropic function. Because the oxytocin concentration in portal blood is approximately 300 times higher than that in peripheral blood, it is likely that the inhibitory action of oxytocin on ACTH secretion is of physiological significance.
Adrenocorticotropic Hormone↗