Clonidine Test Research Articles

Pheochromocytoma in Italy: a multicentric retrospective study.

To conduct an epidemiological study on pheochromocytoma in Italy. Data on 284 patients with pheochromocytoma observed between 1978 and 1997 were collected from 18 Italian centers through a questionnaire reporting epidemiological, clinical, laboratory, radiological and surgical data. 53.6% of the patients were females and 46.4% were males. Thirty-two tumors were discovered as incidental adrenal masses. The most frequent referred symptoms were palpitations (58.1%), headache (51.9%), sweating (48. 8%) and anxiety (35.3%). Their association was present only in 15.5% of patients. Paroxysmal symptoms were reported in 67.1% and hypertensive crises in 59.7% of patients. Normal blood pressure (systolic and diastolic) was present both in the supine and upright positions in 21.1% of patients. Among laboratory assays, urinary vanylmandelic acid (VMA) was the most widely used (58.1%) and was the least sensitive (25% of false negative results). Basal plasma catecholamines were found to be normal in 11.3% of patients but were always elevated when sampled during a hypertensive paroxysm. A clonidine suppression test was performed in 38 patients with no adverse side effects. It gave a false negative response in 2 patients. A glucagon test was performed in 21 patients. It was interrupted for acute hypertension in 52.4% of patients. Only 5/21 patients were normotensive and had normal basal plasma catecholamines. In these patients the test gave a positive response in four (80%). CT (79.6%) and I-MIBG scintigraphy (68.5%) were the most widely used methods for tumor localization. CT sensitivity was 98.9% for intra-adrenal and 90.9% for extra-adrenal tumors. MIBG sensitivity was 88.5%. In the 263 patients who underwent surgery, the tumor was intra-adrenal in 89.4%, extra-adrenal in 8.5%, intra- and extra-adrenal in 2.1%, and bilateral in 11.0% of patients. Malignancy was reported in 9.9% of cases. Surgery caused remission of hypertension in 59.3%, improvement in 26.8%, and no changes in 13. 9% of patients. In the last group the interval between initial symptoms and diagnosis was significantly longer. The present study confirms that the clinical presentation of pheochromocytoma is variable and aspecific. Normotension is often present and often the tumor is discovered incidentally. An indication for the routine use of screening methods more sensitive than urinary VMA is strongly suggested. The clonidine test was found to be safe and should be preferred to the glucagon test which has to be restricted to very selected patients. CT and MIBG scintigraphy are almost always successful in localizing the tumor. Reversal of hypertension by surgery seems to depend on an early diagnosis.

Autonomic function in hypertensive patients with neurovascular compression of the ventrolateral medulla oblongata.

To study whether abnormalities of autonomic function exist in patients with essential hypertension and neurovascular compression (NVC) of the medulla oblongata. We studied 25 untreated patients with essential hypertension (13 men and 12 women, 27-74 years old). High-resolution magnetic resonance imaging and magnetic resonance angiography were used to detect NVC. Twenty-four-hour ambulatory monitoring of blood pressure and electrocardiogram were performed, and the power spectrum of heart rate variability was analyzed. On a separate day, various autonomic activity tests, including mental stress, hand grip, cold pressor, and Valsalva maneuver were performed. Baroreflex sensitivity was calculated from changes of blood pressure and R-R interval during phenylephrine infusion. A clonidine suppression test was also performed, with measurement of plasma catecholamine levels. Fourteen of 25 patients (56%) had NVC (C group), and 11 patients did not have NVC (NC group). There were no significant differences in age, sex, family history, or duration of hypertension between the C and NC groups. Average 24-h systolic blood pressure was similar between the two groups, although 24-h diastolic blood pressure was higher in the C group than the NC group. Daytime, night-time, and 24-h heart rate was significantly higher in the C group than in the NC group. Night-time low frequency/high frequency ratio was slightly higher in the C group. Plasma norepinephrine levels were significantly higher (467 +/- 217 versus 299 +/- 122 pg/ml), and baroflex sensitivity was slightly lower in the C group than in the NC group. Responses of blood pressure and heart rate to mental stress, cold pressor, hand grip, Valsalva maneuver, phenylephrine infusion, and clonidine tests were not significantly different between the two groups. NVC of the medulla oblongata was frequently found in patients with essential hypertension. Patients with NVC appeared to have enhanced sympathetic nervous activity compared with those without the compression.

GH/IGF-I axis in azoospermia in primary and secondary hypogonadism: a study before and during replacement therapy.

The growth hormone/insulin-like growth factor-I (GH/IGF-I) axis was studied in 15 azoospermic patients and in 10 control men. Eight patients were affected by hypergonadotrophic hypogonadism and 7 by hypogonadotrophic hypogonadism. All were studied before and during replacement therapy with testosterone and gonadotrophin, respectively, using the alpha 2 adrenergic agonist, clonidine (clonidine test). The data demonstrate no differences in basal levels for IGF-I and for the GH response to clonidine in azoospermic patients, affected by primary and secondary hypogonadism, before and during replacement therapy when compared with control fertile men. In contrast to some studies which describe a reduced GH response in azoospermia and oligozoospermia, we conclude that basal serum levels of IGF-I and the GH response to clonidine are not impaired in azoospermic patients affected by primary hypogonadism before and after the restoration of normal androgenization, and in azoospermic patients affected by secondary hypogonadism, both before and after restoration of spermatogenesis.

Plasma catecholamines and clonidine test in the differential diagnosis of essential hypertension and pheochromocytoma.

Plasma catecholamines and clonidine test in the differential diagnosis of essential hypertension and pheochromocytoma.

Growth hormone improves body composition, fat utilization, physical strength and agility, and growth in Prader-Willi syndrome: A controlled study

Background: Obesity and hypotonia in children with Prader-Willi syndrome (PWS) are accompanied by abnormal body composition and diminished energy expenditure resembling a growth hormone–deficient state. Hypothalamic dysfunction in PWS often includes decreased growth hormone (GH) secretion, suggesting a possible therapeutic role for exogenous GH treatment. Objectives and methods: After 6 months of observation to determine baseline growth rate, and with the use of a 12-month randomized controlled study design, the effects of GH treatment (1 mg/m 2/d) on growth, body composition, strength and agility, pulmonary function, resting energy expenditure (REE), and fat utilization were assessed in 54 children with PWS (n = 35 treatment and n = 19 control). Percent body fat and bone mineral density were measured by dual x-ray absorptiometry. Indirect calorimetry was used to determine REE and to calculate respiratory quotients. Results: Stimulated levels of GH in response to clonidine testing were low in all patients (peak, 2.0 ng/mL). After 12 months, GH-treated subjects showed significantly increased height velocity Z scores (mean, –1.0 ± 1.7 to 4.6 ± 2.9; P < .001), decreased percent body fat (mean, 46.3% ± 8.4% to 38.3% ± 10.7%; P < .001), and improved respiratory muscle function, physical strength, and agility (sit-ups, weight-lifts, running speed, and coordination). A significant decline in respiratory quotients occurred during GH therapy (0.81 to 0.77, P < .001), but total REE did not change. Conclusions: GH treatment of children with PWS accelerated growth, decreased percent body fat, and increased fat oxidation but did not significantly increase total REE. Improvements in respiratory muscle strength, physical strength, and agility also occurred, suggesting that GH treatment may have value in reducing some physical disabilities experienced by children with PWS. (J Pediatr 1999;134:215-21)

Growth hormone response to the insulin tolerance and clonidine tests in type 1 diabetes

The insulin tolerance test (ITT) is regarded the gold standard for assessing growth hormone (GH) release in adult patients with suspected GH deficiency. Some of these patients also have diabetes mellitus. There are contradictory reports regarding the GH response to ITT in type 1 diabetic patients with varying degrees of metabolic control. This is also true for the clonidine test. We studied ten patients with uncomplicated type 1 diabetes mellitus during periods of poor and improved metabolic control and compared them with ten healthy control subjects. The GH secretion was assessed by an ITT with an insulin infusion of 2.5 mU/kg/min and an intravenous clonidine test. The GH response to ITT was similar during poor and improved metabolic control (mean +/- SEM) (AUC 2327 +/- 616 vs. 2649 +/- 508 microg/l x min) and did not differ from the response in control subjects (AUC 2587 +/- 343 microg/1 x min). The clonidine test induced a significantly greater GH response during poor than during improved metabolic control in the diabetic patients (AUC 2598 +/- 492 vs. 1508 +/- 368 microg/l x min, p < 0.05); this response was greater than in the control subjects (670 +/- 226 x microg/l x min, p < 0.005 vs. improved metabolic control). Thus, the GH response to ITT is similar in diabetic patients with varying degrees of metabolic control and healthy subjects, while the GH response to the clonidine test is higher in the type 1 diabetic patients than in healthy controls.

Dexamethasone in the diagnostic work-up of growth hormone deficiency

OBJECTIVE Acute administration of dexamethasone (dexa) has recently been shown to induce growth hormone (GH) release. To ascertain the efficacy of this stimulus in assessing GH secretory status in children, we tested it in a large group of patients with short stature. METHODS We administered dexamethasone at the dose of 2 mg/m2 to 44 short normal children and 19 GH deficient (GHD) children, either orally or intravenously and compared the results of the dexa-test to the more classical clonidine test. RESULTS The oral dexa-test induced a GH peak similar to the clonidine test (clo) (controls clo: 23.8 ± 7.8 mU/l, median 22.8, range 15.2–45.4 vs. control dexa: 20.6 ± 10.8, median 16.8, range 8–47, P = 0.2. GHD clo: 9.8 ± 2.6, median 9.2, range 6.4–13.4 vs. GHD dexa: 9.4 ± 3.4, median 10.2, range 4.6–14, P = 0.8). Its sensitivity and specificity with respect to the clonidine test were 91% (10/11 GHD) and 65% (15/23 controls), respectively. The GH peak after i.v. dexa was smaller than that after clonidine (control clo: 30.6 ± 14 μg/l, median 24.8, range 14.2–62.4 vs. control dexa: 21.6 ± 5.4, median 21.6, range 11.2–33, P = 0.01. GHD clo: 7.4 ± 4.2, median 8.8, range 0.4–11.8 vs. GHD dexa: 6.4 ± 5.6, median 5.8, range 0.4–16.2, P = 0.17) with sensitivity and specificity of 87% (7/8 GHD) and 90% (19/21 controls), respectively. The lower potency of dexamethasone could account for these figures, since when a different cut-off was used (12 mU/l and 11 mU/l for the oral and i.v. route) both sensitivity and specificity were improved. More data are needed to support these findings and establish a clear cut-off. In the control group, no difference was found between GH peak after oral or i.v. dexa but GH-area under the curve (AUC) was larger for i.v. than for oral dexa. No side effects were noted. CONCLUSIONS Intravenous dexamethasone appears to be a promising stimulus for the detection of GH deficiency in children, particularly for use in outpatients.

Neuroendocrine effect of a short-term treatment with DHEA in postmenopausal women

Objectives: A progressive decline of plasma dehydroepiandrosterone (DHEA) levels occurs in women during aging related to the reduction of adrenocortical secretion. A specific action of DHEA on the central nervous system (CNS) is suggested by the improvement of psychological and physical well-being in postmenopausal women after DHEA supplementation. The aim of the present study was to investigate the neuroendocrine effects of short-term DHEA supplementation in postmenopausal women, evaluating changes of plasma β-endorphin ( β-EP) and growth hormone (GH) before and after oral DHEA (100 mg/day) for 7 days in postmenopausal women ( n=6). Methods: Before and after 7 days of DHEA supplementation, postmenopausal women underwent a neuroendocrine test with clonidine, an α2 presinaptic agonist for adrenergic system, (1.25 mg i.v.). Basal plasma DHEA, androstenedione (A), testosterone (T), estrone (E 1) and estradiol (E 2) levels were evaluated before and after treatment, while plasma β-EP and GH levels were measured before and 15, 30, 45, 60 and 90 min after clonidine injection. Results: Basal plasma β-EP and GH levels did not show a significant difference before and after short-term DHEA administration, while circulating A, T, E 1 and E 2 significantly increased after treatment. The clonidine test induced a significant increase of plasma β-EP levels in women after receiving DHEA supplementation but not before; conversely, plasma GH levels increased both before and after treatment. Conclusions: The present study indicates that short-term DHEA supplementation in postmenopausal women is able to restore the impaired response of pituitary β-EP to clonidine, an α2 presinaptic agonist. According to these data it is possible to hypothesize that DHEA could play a role in the psychological and physical well-being of postmenopausal women acting via a restoration of neuroendocrine control of antero-pituitary β-EP secretion.

Neuroendocrine effects of different estradiol-progestin regimens in postmenopausal women

Objective: New regimens and routes of administration of hormonal replacement therapy (HRT) in climateric women are becoming available. Since there is no information on the neuroendocrine effects of sequential combined treatment with 17 β-estradiol and a progestin, the present study evaluated the neuroendocrine, clinical vasomotor and psychological changes before and after different sequential combined HRT regimens (17 β-estradiol plus nomegestrol acetate, or cyproterone acetate, or vaginal progesterone). Vasomotor and behavioral effects were evaluated by using the Kupperman score, while changes in plasma endorphin ( β-END) levels were used as marker of neuroendocrine effects. Methods: Postmenopausal women ( n=30) were randomly divided into three groups (ten women for each group); all women received continuous 17 β-estradiol (50 mg, transdermal) and each group was sequentially treated with different progestins for 12 days/month: group A, cyproterone acetate (5 mg p.o.); group B, nomegestrol acetate (5 mg p.o.); and group C, progesterone (100 mg, vaginal cream).A group of healthy fertile women ( n=8) served as control. Before and after 6 months of HRT, postmenopausal women underwent an evaluation of subjective Kupperman score and two neuroendocrine tests: (a) naloxone (4 mg i.v.) and (b) clonidine (1.25 mg i.v.). Plasma β-END levels were measured before and at 15, 30, 45, 60 and 90 min after drug injection. Control women were studied by administering the two neuroendocrine tests only once. Results: Postmenopausal women before HRT showed a pathological Kupperman and no changes of plasma β-END levels in response to the clonidine and naloxone tests score. On the contrary the increase was significant in healthy women. In each of the three groups of treated women both naloxone and clonidine tests induced a significant increase in plasma β-END levels ( P<0.01). After 6 months of HRT, an improvement of vasomotor and psychological symptoms was shown by a decrease of Kupperman score. Conclusions: The present study indicates that sequential treatment with transdermal 17 β-estradiol and progestin, no matter which progestin was used, restores the β-END release, improves vasomotor and psychological symptoms.

Growth deficiency in polytransfused beta-thalassaemia patients is not growth hormone dependent.

Growth deficiency is commonly seen in polytransfused beta-thalassaemia patients, especially in adolescence. It is not completely dependent on the lack of their pubertal growth spurt. GH impairment at different levels (hypothalamic or pituitary) and/or a reduced IGF-1 synthesis have been suggested the main causes of stunted growth in these patients. We evaluated the relationship between GH reserve and growth in short beta-thalassaemia patients. Twenty-nine short patients (height < -1.8 SDS for chronological age) were divided into two groups (low and normal responders) on the basis of their GH peak during insulin and clonidine tests (< or = and > 20 mU/l, respectively). All but one low responders underwent the GHRH test to exclude the impairment of somatotroph function and in eight of them an IGF-1 generation test was also performed. The two groups were compared with each other with respect to growth (height deficiency, height velocity, bone age and bone delay), haematological characteristics (serum ferritin levels, age at the start both of low (subcutaneous) s.c. infusion of desferrioxamine and of transfusional therapy) and serum IGF-1 and IGF-1 binding protein 3 levels. Thirteen patients (45%) (11 males, two females) were low responders, all but two having serum IGF-1 < 5th centile (< 0.1 centile in 42%); the GHRH test excluded the impairment of somatotroph function in 8/12. Height deficiency, serum ferritin levels, and age at the start of s.c. chelating therapy did not differ in low compared to normal responders. Height was negatively correlated both with the age at the start of s.c. chelating therapy and with serum ferritin levels. The reduction of GH reserve, more frequently due to a hypothalamic than to a pituitary dysfunction, is frequent in polytransfused beta-thalassaemia patients, especially in males. The height function is not related to the GH reserve, given the current methods for testing GH reserve. Late start of s.c. chelating therapy as well as haemosiderosis seem to play a role in the height deficiency, but not in GH reserve. Impairment of GH secretory reserve, therefore, cannot be considered the main cause of height deficiency in these patients.

Hypothalamic versus pituitary dysfunction in Down's syndrome as cause of growth retardation.

We have found that some children with Down's syndrome (DS) have growth retardation secondary to growth hormone (GH) deficiency. To test the hypothesis that hypothalamic dysfunction is the primary cause for GH deficiency and growth retardation, hypothalamic-pituitary responses of serum GH concentrations to levodopa and clonidine as well as pituitary responses in serum GH concentrations to growth-hormone-releasing hormone (GHRH) were analysed in 14 prepubertal children with DS. Levodopa and clonidine were given, and blood was drawn for determining serum GH levels. Seven prepubertal control children had both levodopa and clonidine tests done. The delta serum GH during levodopa was 5.7 +/- 6.3 ng ml-1 in DS and 13.1 +/- 9.8 ng ml-1 in controls. The delta serum GH during clonidine administration was 3.0 +/- 3.2 ng ml-1 in DS and 17.3 +/- 5.6 ng ml-1 in controls. Children with DS had a significantly lower response to levodopa and clonidine, compared with controls by the Mann-Whitney U-test (P < 0.03 and P < 0.009, respectively). Growth-hormone-releasing hormone was given at 1 microgram kg-1 i.v. bolus and bloods for GH were drawn at-15, 0, 15, 30, 60, 90 and 120 min in 14 subjects with DS and 24 normal controls, both groups prepubertal. The mean delta serum GH concentration in DS was 53.6 +/- 38.3 ng ml-1, and it was 35.6 +/- 25.1 ng ml-1 in controls with P < 0.23 non-significant by the Mann-Whitney U-test. These results indicate that levodopa and clonidine (drugs stimulating hypothalamic GHRH release and secondary pituitary GH release in normal individuals) do not stimulate GH release in DS. Furthermore, normal GH response to GHRH in DS indicates normal pituitary function (normal somatotroph response to GHRH) and supports hypothalamic dysfunction in DS.

Reproducibility and Comparison of Growth Hormone Secretion Tests

To assess the degree of reproducibility of spontaneous GH secretion and pharmacological tests we studied 15 prepubertal children with short stature and abnormal growth rate. In all children, spontaneous overnight GH secretion was measured followed by a clonidine test in 8 children and an arginine test in the remaining 7. The same protocol was repeated a week later. Intra-individual variability of GH secretion in both physiological and pharmacological tests was expressed as the coefficient of variation (CV%). No significant difference was found between the first and second value of parameters of spontaneous GH secretion. Maximum spontaneous GH peak (MS) and mean 12-h GH concentration (MGH) correlated significantly (r = 0.78, p < 0.001). Mean CV% of all parameters of repeated GH profiles (around 30%) were lower than those of provocative tests (around 70%) (p < 0.05). No significant difference was found between CV% of clonidine and arginine tests. There was no correlation between MGH or MS and GH response to provocative test in the same child. We found a significant correlation between the log transformed maximum provocative GH response to the arginine test and the length of the time interval (in min) from the end of the last GH peak in the previous profile to the time zero of the provocative test (r = 0.60, p < 0.05). This relationship was not found for the clonidine test. We conclude that spontaneous GH secretion in children with short stature is more reproducible than stimulated GH response with a week's difference. Perhaps the higher variability of provocative GH secretion may be related to the state of the endogenous hypothalamic rhythm of both GHRH and somatostatin release at the time of the test.

Benzodiazepines: Tolerability in Elderly Patients

Aging is a physiological process that shares many behavioral, biochemical and neuroendocrine phenomena with the pathophysiological situation of unresolved stress, as well as with a pharmacologically induced syndrome resulting from chronic benzodiazepine (BZ) consumption. Behavioral findings include symptoms such as drowsiness, ataxia, fatigue, confusion, weakness, dizziness, vertigo, syncope, reversible dementia, depression, impairment of intellectual, psychomotor and sexual function, agitation, auditory and visual hallucinations, paranoid ideation, panic, delirium, depersonalization, sleepwalking, aggressivity, orthostatic hypotension, and insomnia. Neuroendocrine findings include: central depletion of noradrenaline (NA), dopamine, adrenaline (AD), and serotonin (5-HT); reduction in the ratio of circulating NA/AD as well as platelet 5-HT and increase of AD, plasma free 5-HT and cortisol. These disturbances together with the increased platelet aggregability observed in the three groups are typical of unresolved-stress situations. Immunological findings include significant reduction of peripheral T lymphocytes (CD3, CD4, CD8) and the CD4/CD8 ratio, CD16 and gamma-delta cells. On the other hand, the three groups (elderly subjects, subjects faced with unresolved stress, and BZ consumers) show increase of the CD57 lymphocyte subset as well as natural killer cytotoxicity. Alterations of several biological markers have also been found, specifically in the oral glucose tolerance test, the intramuscular clonidine test, and the supine/orthostasis/exercise test. From a clinical point of view, the three groups appear to be more susceptible to the appearance and progression of many acute and chronic diseases (infectious and malignant diseases). As a result, chronic consumption of BZs should be avoided in both the elderly and subjects in unresolved-stress situations.

Circadian growth hormone secretion in short multitransfused prepubertal children with thalassaemia major

Growth hormone (GH) secretion was determined by evaluating circadian GH profiles for 24 h and GH responses to clonidine stimulation test and insulin-stimulated hypoglycaemia (ITT), in nine prepubertal children with beta-thalassaemia major (TM) and 17 with non-GH deficient short stature (NGHDSS). The TM children were multitransfused and had early and intensive chelation therapy. All patients had normal hypoglycaemia to ITT, with peak GH levels of 15.71 +/- 5.86 ng/ml for children with NGHDSS and 13.91 +/- 7.20 ng/ml for children with TM. Peak GH levels during a clonidine test were 17.54 +/- 5.30 and 17.15 +/- 1.38 ng/ml, respectively. The GH peak parameters such as the number of peaks, the integrated GH concentration and the area under the curve (AUC) were similar in both groups of children and reflected the total 24-h secretion and the daily and nocturnal secretion separately. An abnormal 24-h GH profile compatible with the diagnosis of endogenous neurosecretory GH dysfunction was found in only two out of nine children with TM and in four out of seven children with NGHDSS. Our data suggest that growth hormone neurosecretory dysfunction is not a universal finding in children with thalassaemia major but might depend on the degree of iron deposit in the pituitary.

Catecholaminergic function and P300 amplitude in major depressive disorder (P300 and catecholamines)

The neurobiology of P300 is still a subject of controversy. P300 amplitude appears to be modulated by multiple neurotransmitter systems, especially dopaminergic, noradrenergic as well as cholinergic and GABAergic. In this study, we investigated the relationship between P300 amplitude and catecholaminergic neurotransmission as assessed by the growth hormone (GH) response to clonidine and apomorphine challenges in 20 major depressive patients. Results showed a correlation of P300 amplitude with the apomorphine test ( r = 0.54; P = 0.01), but not with the clonidine test ( r = 0.22; NS). This study supports a role for dopamine in the neurobiological modulation of P300 amplitude.

α2-Adrenergic receptor sensitivity in panic disorder: I

Baseline levels of GH and somatomedin C (SmC) and GH responses to GHRH (1 microgram/kg b.w.) and to clonidine (150 micrograms) were measured in 10 outpatients with panic disorder before and after 30 days of 2-2.5 mg of alprazolam therapy, and in 10 psychophysically healthy controls. Basal levels of GH were normal in the patients and those of SmC significantly elevated, both before and after therapy. Basal GH responses to GHRH stimulation were normal and did not change change after alprazolam treatment. Basal GH responses to clonidine stimulation were blunted in the patients and improved after therapy, in parallel with an amelioration of the psychopathology. Our data suggest that adrenoceptor sensitivity, investigated by the clonidine test, is reduced in panic disorder.

Spike-and-wave epilepsy in rats: sex differences and inheritance of physiological traits.

Spontaneously occurring spike-and-wave patterns were examined in seven to eight-month-old rats of the inbred Fischer 344 and Brown Norway strains and their F1 and F2 hybrids. Neocortical activity and movement were monitored for 12 night h. Spike-and-wave episodes were identified by a three-layer back-propagation neural network. The incidence, average duration and total duration of spike-and-wave episodes were significantly higher in F1 males and F2 hybrids than in the parental strains. Male rats of the Brown Norway strain had significantly more and longer episodes than females, whereas no sex differences were present in Fischer rats. The average intraepisodic frequency of spike-and-wave patterns was significantly lower in Fischer rats than in the other groups and significantly higher in males than females. Tremor (myoclonic movements) associated with spike-and-wave episodes was absent or of very small amplitude in Fischer rats but frequent and of large amplitude in Brown Norway rats and their F1 and F2 descendants. Most of the interstrain differences were limited to male rats. Spike-and-wave episodes recurred at predictable short-term (10-30 s) and long-term (15-30 min) periods. The long-term oscillation corresponded to a similar fluctuation of motor activity. The maximum probability of spike-and-wave patterns occurred at a relatively narrow range of delta power (0-3.1 Hz) of the background EEG activity. Systemic administration of the adrenergic alpha-2 agonist, clonidine, increased the incidence of spike-and-wave episodes several-fold. The total duration of spike-and-wave episodes in the clonidine sessions (15 min) and night sessions (12 h test) correlated significantly. We suggest that several genes interact with maturational, environmental and endocrine factors, resulting in sex differences, and produce the variety of EEG and behavioral findings encountered. In addition, we submit that the clonidine test may be useful in genetic investigations of human absence epilepsies. The findings of this work demonstrate that genetic manipulation of rodents is a promising method for producing analogous models for the various forms of human absence epilepsies.

30 COMPARISON AND REPRODUCIBILITY OF GROWTH HORMONE (GH) SECRETION TESTS

There is not agreement on which is the most useful and reproducible test to diagnose GH deficiency. To asses the degree of reproductiveness of physiological and pharmacological test we studied 15 prepuberal childre(14 ♂: l♀;CA (X±SD) 10.5±2.0 years; BA 7.75±2.3 years with short stature(Height SDS -1.9to -3.6) and abnormal growth rate. In all children spontaneous overninght GH secretion (SGH)was performed, followed by clonidine test(Clo)in 8 children and arginine test(Arg)in 7. The same protocol was repeated a week later, GH was measured by RIA. Variability was expressed as the coefficient of variation (CV) of all repeated tests. Results: CV for mean SGH were significantly lower than those for Clo and Arg (p 2.5ng/ml in both oportunities(5 of GA;5 of GB and 3 GC).1 patient showed values <2.5 ng /ml in two ocassions (GC) and 1 had variable means of SGH (GB). Conclusions: This study shows that SGH is most reproducible test. The lack of correlation between CV indicates that variability may be characteistic of each test. Normality of the GH secretory status could not be stablished with the tests used.

The influence of carbamazepine on sleep-EEG and the clonidine test in healthy subjects: Results of a preliminary study

A study of healthy volunteers was peformed with the aim of testing the hypothesis that carbamazepine suppresses REM sleep. Concerning GH secretion in the clonidine test, our study was considered exploratory

Aetiological factors involved in the low response to gonadotrophins in infertile women with normal basal serum follicle stimulating hormone levels

This study was designed to investigate possible aetiological factors involved in the low response to gonadotrophins in women with normal basal serum follicle stimulating hormone (FSH) concentrations, stimulated for assisted reproduction. Nine of these patients with normal basal serum FSH and 22 normal controls (five of whom had had a normal response to previous gonadotrophin stimulation) were prospectively subjected to: (i) transvaginal pulsed colour Doppler ultrasound evaluation of the vessels surrounding the dominant follicle for blood flow impedance analysis, (ii) the clonidine test to explore the ability of the pituitary to release growth hormone, and (iii) detection of anti-granulosa cell auto-antibodies in blood using an enzyme-linked immunosorbent assay (ELISA). The pulsatility and resistance indices (PI, RI) were significantly (P < 0.01) higher in the women with low responses as compared to the controls on days -1 and 0 (day 0 = ovulation). Seven out of the nine low responders were out of the range calculated for normal values after evaluation of the controls. A significant (P < 0.05) decrease in the secretion of growth hormone 60-90 min after clonidine ingestion was observed in the low responders as compared to five controls with previous normal response to ovarian stimulation. Six out of the nine low responders showed a negative clonidine test. No increase in anti-granulosa cell auto-antibodies was observed in the low responders as compared to the controls, including normal responders. In conclusion, an abnormal follicular blood flow impedance in the natural cycle may be related to low responses to gonadotrophins in patients with normal serum FSH concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)