NOCTURNAL URINARY MELATONIN EXCRETION AND PLASMA CORTISOL LEVELS IN CHILDREN AND ADOLESCENTS AFTER A SINGLE ORAL DOSE OF DEXAMETHASONE

In the present study, the possible relationship between melatonin secretion as reflected by nocturnal melatonin excretion (2000 h-0800 h) and the pituitary-adrenocortical axis was investigated. Nocturnal urinary melatonin excretion and plasma cortisol levels were determined in 41 children with weight problems before and after a single oral dose of dexamethasone. A first group of 15 individuals with normal cortisol cycle (12.2 +/- 1.4 at 0800 h and 3.1 +/- 0.5 micrograms/100 ml at 1700 h), and levels below 1.0 microgram/100 ml after dexamethasone, showed a highly significant increase in melatonin excretion during the night following dexamethasone treatment (63.5 +/- 5.5 ng/12 h vs 33.6 +/- 3.0 for the control night, P less than 0.001). This increase was observed from prepuberty to young adulthood (pubertal stages PI-PV). In a second group of 16 subjects with mean cortisol levels similar at 0800 h and 1700 h (10.7 +/- 1.3 and 9.3 +/- 1.5 micrograms/100 ml respectively), but with a normal cortisol suppression after dexamethasone administration, nocturnal melatonin excretion increased from 21.2 +/- 2.1 to 33.4 +/- 3.0 ng/12 h (P less than 0.01). A significant increase was found in prepubertal children (PI) whereas no change was observed at the end of pubertal development (stages PIV-PV). A third group of 10 patients with both low amplitude cortisol cycles (16.2 +/- 2.5 and 10.8 +/- 2.4 micrograms/100 ml) and abnormal cortisol suppression after dexamethasone administration (9.1 +/- 2.4 micrograms/100 ml), showed no increase in melatonin excretion (24.2 +/- 2.7 and 24.9 +/- 3.7 ng/12 h).(ABSTRACT TRUNCATED AT 250 WORDS)     

PLASMA PROLACTIN LEVELS AFTER ACUTE AND SUBCHRONIC ORAL ADMINISTRATION OF DOMPERIDONE AND OF METOCLOPRAMIDE: A CROSS-OVER STUDY IN HEALTHY VOLUNTEERS

Domperidone is a new potent anti-emetic drug which, in contrast with metoclo-pramide, does not cross the blood brain barrier. The aim of the present study was to find out whether peripheral dopaminergic blockage by domperidone causes prolactin release, and if so, whether this prolactin release persists during longer-term treatment. For comparison, metoclopramide, which blocks both peripheral and central dopamine receptors, was studied using a cross-over trial design. After acute oral administration of both drugs, prolactin levels increased 10-fold. After further treatment with metoclopramide the prolactin levels were further increased to 15-fold, but after prolonged administration of domperidone a decrease to a plasma level 6-fold higher than basal was observed. The clinical implications of these findings are discussed.     

经皮二尖瓣球囊扩张术前后血浆降钙素基因相关肽水平研究

为了解经皮二尖瓣球囊扩张术（ＰＢＭＶ）前后血浆降钙素基因相关肽（ＣＧＲＰ）水平，采用放免法测定３０例风湿性二尖瓣狭窄患者ＰＢＭＶ前后的血浆ＣＧＲＰ和内皮素水平，与对照组比较，并与左房内径、二尖瓣口面积和血液动力学参数作相关分析，旨在探讨血浆ＣＧＲＰ水平与二尖瓣狭窄和ＰＢＭＶ的关系。结果显示：术前血浆ＣＧＲＰ水平显著低于对照组（分别为５．６３±１．０１和２２．２９±６．４２ｎｇ／Ｌ，Ｐ＜０．００１），术后第１天明显升高（１２．１５±３．３２ｎｇ／Ｌ，Ｐ＜０．００１），以后继续升高，而血浆内皮素水平则呈相反变化（Ｐ＜０．００１）；ＣＧＲＰ与内皮素的血浆含量呈显著负相关（ｒ＝－０．４２７，Ｐ＜０．０１）；血浆ＣＧＲＰ水平与心脏指数呈显著正相关（ｒ＝０．７０３，Ｐ＜０．００１），与平均肺动脉压、平均右房压和平均左房压呈显著负相关（ｒ分别为－０．６０１、－０．５３５和－０．５９８，Ｐ均＜０．００１）；心功能越差，血浆ＣＧＲＰ水平越低（Ｐ＜０．００１）。提示ＣＧＲＰ在二尖瓣狭窄的病理生理改变中起着重要作用，其血浆水平可作为判断二尖瓣狭窄病情和ＰＢＭＶ疗效的一个指标。     

LONG-LASTING LOWERING OF SERUM GROWTH HORMONE AND PROLACTIN LEVELS BY SINGLE AND REPETITIVE CABERGOLINE ADMINISTRATION IN DOPAMINE-RESPONSIVE ACROMEGALIC PATIENTS

Cabergoline, the new long-acting dopaminergic ergoline derivative, was given orally in single doses of 0.3 and 0.6 mg to eight dopamine-responsive acromegalic patients. Serum GH and PRL levels were determined before treatment, 3, 4, and 6 h and 1, 3, 5, 7 and 14 days after treatment. A control test with a single oral dose of 2.5 mg of bromocriptine was also performed. Cabergoline induced a marked fall in serum PRL level, starting within 3 h and continuing for 7 days after administering 0.3 mg, and for 14 days after 0.6 mg. The mean maximal decrease was 49% after 0.3 mg and 63% after 0.6 mg and occurred after 24 h in both cases. The latter was of similar magnitude to that induced by bromocriptine (67% at 4 h). Serum GH levels did not change after 0.3 mg of cabergoline, but decreased significantly from 3 h to 3 days after 0.6 mg of the compound with a mean maximal decrease of 42% after 24 h, and from 3 to 6 h after giving bromocriptine (mean maximal decrease 63% at 4 h). Once a week repeated administration of 0.3-0.6 mg of cabergoline was carried out in six patients, five of whom had completed the acute study; a normalization of serum GH and insulin-like growth factor I (IGF-I) levels occurred in three patients, one of whom had very high pretreatment values. In three poorly or nonresponsive patients, a better response, as assessed by both GH and IGF-I levels, was induced by increasing the dose up to 0.6 mg twice or 0.4 mg three times a week; in one case this was associated with marked tumour shrinkage. Sustained normalization of PRL levels was achieved in all cases. These data indicate that a single dose of 0.6 mg of cabergoline inhibits GH as well as PRL secretion in dopamine-responsive acromegalic patients and suggests that doses of 0.3-0.6 mg once to three times a week may prove suitable for treatment of this condition.     

THE EFFECT OF PUBERTY AND SHORT-TERM ORAL ADMINISTRATION OF TESTOSTERONE UNDECANOATE ON GH TESTS AND SEX-STEROID RELATED PLASMA COMPOUNDS IN GH DEFICIENT PATIENTS

In twelve boys and two girls, with idiopathic (partial) growth hormone deficiency diagnosed at prepubertal age, we studied the effect of spontaneous puberty (six patients) as well as the effect of sex-steroid priming (eight patients). Six boys received testosterone undecanoate and two girls ethinyloestradiol for 5 days. Two pubertal patients showed a normal GH response, the patients primed with testosterone or oestrogen did not, despite a distinct effect on sex-steroid related plasma compounds. Reevaluation of GH status appears to be worthwhile in GH deficient patients presenting with short stature, growth deceleration at an early pubertal age and delayed sexual maturation. Sex-steroid priming is unlikely to alter the outcome of GH testing, whenever marked growth deceleration is evident at prepubertal age.     

GLUCOSE TOLERANCE AND PLASMA IMMUNOREACTIVE INSULIN LEVELS IN ACROMEGALICS BEFORE AND AFTER SELECTIVE TRANSSPHENOIDAL SURGERY

The glucose and immunoreactive insulin (IRI) responses to a 100 g oral glucose tolerance test (oGTT) administered to 23 acromegalic patients before and after transsphenoidal adenomectomy and to a sex and age-matched control group were studied. The preoperative growth hormone levels, ranging from 11 to 360 mU/l, had normalized (i.e. less than or equal to 5 mU/l) after surgery in all cases. Before surgery paradoxical increases in the GH level, either after i.v. TRH injection or during the oGTT were seen in 14 patients. After surgery, the paradoxical reaction to the oGTT had normalized in all cases and the increase measured after the TRH injection normalized in nine out of 12 cases. The disturbed glucose tolerance (either impaired tolerance or frank diabetes) was cured by surgery. The plasma glucose levels determined 1 and 2 years after surgery did not differ from those found for the control group. Preoperative plasma IRI levels were significantly elevated, whereas after surgery the IRI levels had decreased. Fasting levels were normalized in all patients. Two years after surgery, eight patients still showed some abnormalities of the insulin secretion (as revealed by the integrated sum and the maximum increment in IRI levels during the oGTT) despite the presence of normal circulating GH levels and a normalized paradoxical reaction to TRH. The data show that after normalization of GH levels in acromegalics, increased insulin secretion may still occur after glucose ingestion in some patients. It is suggested that this abnormality could be the result of an increased pancreatic islet beta-cell mass, as a persisting abnormality of the acromegalic state, although peripheral insulin resistance cannot be excluded totally.     

CHANGES OF URINARY CYCLIC AMP EXCRETION AND PLASMA PARATHYROID HORMONE LEVELS BEFORE AND AFTER PARATHYROIDECTOMY IN PATIENTS WITH PRIMARY HYPERPARATHYROIDISM

Urinary cyclic AMP excretion and plasma parathyroid hormone(PTH) levels were examined in three patients with primary hyperparathyroidism before and after parathyroidectomy. Plasma PTH and urinary cyclic AMP in the individual patients decreased in parallel following parathyroidectomy. During surgery there was a statistically significant correlation between PTH levels and cyclic AMP excretion in individual patients. These findings support the claim that the rate of urinary cyclic AMP excretion reflects endogenous PTH activity in patients with primary hyperparathyroidism.     

EFFECT OF WEIGHT-LOSS ON PLASMA AND URINARY LEVELS OF URIC ACID

Fifteen overweight subjects, ten men and five women, six of them with gout, reduced their weight on a low-calorie diet. Plasma and urinary levels of uric acid were estimated while the subjects were taking a low-purine diet before and after the period of weight-loss, which ranged from 4 to 22 kg. After weight-loss, plasma-uric-acid fell in twelve of the fifteen subjects by a mean decrease of 0·8 mg. per 100 ml. Changes in urinary urate were not consistent. This influence of body-weight upon the plasma level of uric acid may be responsible for the association between these two variables which has been observed in epidemiological and clinical studies.     

BASAL AND SALINE-STIMULATED LEVELS OF PLASMA ATRIAL NATRIURETIC FACTOR IN ACROMEGALY

We have studied plasma ANF before and after a 4-h intravenous infusion of normal saline in eight subjects with active acromegaly and in eight age and sex-matched control subjects. Plasma ANF, serum aldosterone and blood pressure were measured basally and after 2 and 4 h and plasma renin activity basally and after 4 h. Basal plasma ANF was similar in each group (4.4 +/- 1.5 pmol/l (mean +/- SEM) in acromegalic subjects and 5.3 +/- 0.7 pmol/l in controls NS). Plasma ANF did not rise significantly after saline in the acromegalic group (2-h value, 5.9 +/- 0.9; 4-h value, 5.1 +/- 0.9 pmol/l) but did rise significantly in the control group (2-h value, 8.9 +/- 1.9; 4-h value 9.5 +/- 1.3 pmol/l, both values P less than 0.05 vs basal level). The 4-h ANF value was significantly higher in the control group than in the acromegalic group (P less than 0.05). Basal and stimulated serum aldosterone values were similar in the two groups. Plasma renin activity suppressed to a lesser extent in the acromegalic group after 4 h. The facts that basal plasma ANF was not raised in acromegalic subjects and did not respond to saline stimulation demonstrate that an abnormality of ANF control may be an important factor in the aetiology of the expanded sodium status of patients with acromegaly and hence may contribute to the hypertension seen in patients with growth hormone excess.     

CSF AND PLASMA SOMATOSTATIN LEVELS IN ACROMEGALY

Cerebrospinal fluid (CSF) and plasma levels of somatostatin have been measured in patients with active acromegaly and the results compared to those obtained in patients with non-endocrine diseases. Plasma levels have also been studied in acromegalics given oral glucose. The mean CSF somatostatin level in twenty patients without endocrine disease was 76 pg/ml (range 46-112) which did not differ significantly from that found in eight acromegalics (mean 87 pg/ml, range 48-160). Plasma somatostatin in twenty-two acromegalic patients on no medical treatment was 43 pg/ml (range 9-113), not significantly different from values in a normal control population. There were no differences in the somatostatin levels of non-diabetic acromegalics. After oral glucose, there was a rise in circulating somatostatin in eleven out of twelve acromegalic patients, and this rise did not differ from that seen in normal subjects. It is probable that altered somatostatin secretion is neither the cause nor the result of acromegaly; however it is possible that local changes in somatostatin concentration which are not reflected in peripheral plasma or CSF levels may occur near the site of its production.     

人血浆抗利尿激素的生理及临床初步研究

本文采用放射免疫法测定10例正常人、14例中枢性尿崩症病人、1例肾性尿崩症病人和1例SIADH病人的血浆AVP水平,发现正常人血浆AVP和血浆渗透压(Osm)明显正相关,血浆Osm每升高3.3mmol/L,血浆AVP相应升高1.0ng/L。血浆AVP生理波动范围为0.9±0.3～5.2±2.7ng/L,血浆AVP开始分泌的血浆Osm水平为280mmol/L。血浆AVP每升高1.0ng/L,尿Osm相应升高156mmol/L,当血浆AVP升高至5.2ng/L后,尿Osm达951mmol/L,此时血浆AVP即使再升高,尿Osm也不再升高。     

TREATMENT OF SYSTEMIC VASCULITIS WITH CYCLOPHOSPHAMIDE AND STEROIDS: DAILY ORAL LOW-DOSE CYCLOPHOSPHAMIDE ADMINISTRATION AFTER FAILURE OF A PULSE INTRAVENOUS HIGH-DOSE REGIMEN IN FOUR PATIENTS

The efficacy of cyclophosphamide (CY) in the treatment of severesystemic vasculitis has been demonstrated, but its optimal administrationregimen remains to be defined. The four patients described participatedin prospective therapeutic trials of polyarteritis nodosa (PAN)without hepatitis B infection markers, Churg-Strauss syndrome(CSS) and Wegener's granulomatosis (WG) and received daily orallow-dose CY after failure of a monthly pulse regimen. Thesepatients were included in this study because of failure to induceclinical remission (two patients) and relapse during the courseof treatment (two patients). The results were good with initialclinical remission in three patients and stabilization in one.One patient with WG relapsed 10 months after changing therapeutics.The advantages of the different administration protocols arediscussed. KEY WORDS: Polyarteritis nodosa, Churg–Strauss syndrome, Wegener's granulomatosis, Cyclophosphamide     

心血管应激和芬太尼对血浆心钠素水平的影响

本实验探讨全麻气管插管心血管应激及芬太尼作用对血浆心纳素水平的影响。结果显示，实验组气管插管心血管应激反应明显，血浆心钠素水平伴随升高，且与血压心率的增加呈高度正相关关系。而对照组在给予６μ８·ｋｇ（－１）芬太尼抑制气管插管应激反应时，插管期间循环兴奋性明显减弱，血浆心钠素水平亦未见升高。因此说明：①血浆心钠素水平与气管插管心血管应激程度密切相关，是气管插管应激指标之一；②芬太尼不参与人类血浆心钠素水平的调节。     

PLASMA CORTICOTROPHIN LEVELS DURING INSULIN-HYPOGLYCAEMIA : COMPARISON OF RADIOIMMUNOASSAY AND CYTOCHEMICAL BIOASSAY

Development of a highly sensitive bioassay for ACTH has enabled bioassayable ACTH to be measured in plasma during the course of the insulin hypoglycaemia test for the first time. Comparison with radioimmunoassay (RIA) on the same plasma samples shows that the latter consistently overstimates the true, or biologically active, ACTH level. This overstimate appears to be most marked when ACTH levels are highest and during the fall in plasma levels which occurs following the ACTH peak. This may limit the value of the RIA of ACTH, in some situations.