EFFECTS OF HIGH-DOSE AND LOW-DOSE NALOXONE ON PLASMA ACTH IN PATIENTS WITH ACTH HYPERSECRETION

The effect of a high (5.4 mg/h) and a low (0.8 mg/h) dose of naloxone (i.v. over a period of 90 min) on ACTH secretion was compared with placebo in patients with Addison's disease, congenital adrenal hyperplasia, Cushing's disease or Nelson's syndrome. In seven patients with primary adrenal insufficiency the high dose of naloxone provoked a significant increase of plasma ACTH concentrations (P less than 0.02) whereas the low dose of naloxone failed to influence ACTH secretion. In six patients with ACTH dependent Cushing's disease or Nelson's syndrome both doses failed to alter plasma ACTH levels. These results support the concept of inhibitory delta- or kappa-opiate receptors in the regulation of ACTH secretion. In patients with Cushing's disease or Nelson's syndrome ACTH secretion is insensitive to naloxone, presumably because of an autonomous pituitary adenoma or hypothalamic derangement.     

OPIATE MODULATION OF THE PITUITARY-ADRENAL AXIS: EFFECTS OF STRESS AND CIRCADIAN RHYTHM

The opiate control of the pituitary-adrenal axis has been investigated in normal subjects. The infusion of 1 mg of the met-enkephalin analogue, DAMME, led to a fall in circulating cortisol in spite of a fall in blood pressure. Conversley, 16 mg of the opiate antagonist, naloxone led to brisk and pronounced elevations in plasma ACTH, lipotrophin (LPH) and cortisol. The rise above basal levels was consistent, irrespective of whether the infusion was given at 09.00, 18.00, or 23.00 h; the peak response obtained was significantly less at 23.00 h than at either 09.00 or 18.00 h. Finally, insulin-induced hypoglycaemia (0.15 u/kg) or naloxone (25 mg) produced a similar rise in plasma cortisol which was no different when the two stimuli were combined. It is suggested that there is a constant tonic inhibition of the pituitary-adrenal axis by endogenous opiates throughout 24 h, and that the circadian rhythm of ACTH/LPH secretion is not due to changes in opiate tone. However, disinhibition of this tone is likely to be responsible, at least in part, for the rise in cortisol in response to hypoglycaemic stress.     

RESPONSE OF PITUITARY-ADRENAL AXIS TO CORTICOTROPHIN RELEASING HORMONE IN PATIENTS WITH CUSHING'S DISEASE BEFORE AND AFTER KETOCONAZOLE TREATMENT

Ketoconazole is an antimycotic agent and a potent inhibitor of gonadal and adrenal steroidogenesis. It has been used successfully as a palliative treatment of Cushing's syndrome due to its ability to lower Cortisol production. However, the effects of ketoconazole on ACTH and aldosterone secretion have not yet been clarified. We evaluated the effect of ovine corticotrophin releasing hormone (oCRH) (100 μg bolus) on plasma ACTH, Cortisol and aldosterone levels in six patients with Cushing's disease before and after 4 to 6 weeks of treatment with ketoconazole 600 mg/d. Before treatment, plasma Cortisol levels were high and significantly increased after oCRH stimulation in all cases, while various patterns of aldosterone secretion were observed. Patients with higher levels showed a greater response to oCRH, while two patients with very low aldosterone showed no response. ACTH showed a marked rise after oCRH administration in all patients with a maximum peak at 30-45 min. After ketoconazole treatment, both plasma Cortisol and aldosterone were lowered and their response to oCRH was impaired. Basal ACTH levels were increased in four patients and ACTH response to oCRH was enhanced in all, compared to pretreatment. These findings confirm the inhibitory action of ketoconazole on basal and stimulated Cortisol secretion. A similar inhibition affected aldosterone production, indicating that ketoconazole also interferes with the mineralocorti-coid pathway. The enhanced response of ACTH to oCRH after the administration of ketoconazole argues against an inhibitory effect of this agent at the pituitary level and might best be explained by reduced negative Cortisol feedback.     

THE EFFECT OF LOW DOSES OF PREDNISOLONE COMPARED WITH PLACEBO ON FUNCTION AND ON THE HYPOTHALAMIC PITUITARY ADRENAL AXIS IN PATIENTS WITH RHEUMATOID ARTHRITIS

A double-blind trial of prednisolone in patients with rheumatoidarthritis using doses of zero, 3 mg and 5 mg is reported. Patientson a dose of 3 mg derived little sustained benefit but subjectson the higher dose showed some improvement which did not lastmore than two years. Mild suppression of the hypothalamo-pituitary-adrenalaxis occurred in both steroid-treated groups. ^*Present address: Department of Rheumatology and Rehabilitation,The General Infirmary, Leeds. Present address: Department of Chemical Pathology, King's CollegeHospital, London     

A NEW FAMILY WITH DEXAMETHASONE-SUPPRESSIBLE HYPERALDOSTERONISM: ALDOSTERONE UNRESPONSIVENESS TO ANGIOTENSIN II

A family with nine siblings in which three siblings have been shown to have dexamethasone-suppressible hyperaldosteronism was studied. All three showed no significant changes of plasma aldosterone during angiotensin II infusion at incremental rates under baseline conditions. After dexamethasone administration (2 mg/d for 4 weeks) plasma renin activity (PRA) rose to normal-supranormal range, while plasma and urinary aldosterone were maintained at low-normal levels. No restoration of aldosterone response to angiotensin II was observed on dexamethasone. Two other siblings were found to be hypertensive with normal baseline data; however, both showed plasma aldosterone hyperresponsiveness to ACTH. In the four normotensive siblings aldosterone response to ACTH was normal. The family pedigree was consistent with autosomal dominant transmission of the disorder. HLA typing showed haplotype A3 Bw35 in all five hypertensive sibs and in one normotensive. In conclusion, low aldosterone compared to PRA, and plasma aldosterone unresponsiveness to angiotensin II infusion before and during dexamethasone, show functional impairment, at least temporary, of the zona glomerulosa. These findings support the hypothesis that aldosterone may be derived from the zona fasciculata in this disorder.     

食道曲张静脉套扎术对肝硬化患者门静脉血流动力学的影响

目的：了解食道曲张静脉套扎术（ＥＶＬ）后门静脉血流动力学改变与临床的关系。方法：采用彩色多普勒对２５例肝硬化患者内镜下ＥＶＬ前后的门静脉血流动力学改变进行测定。结果：ＥＶＬ治疗２周后肝硬化患者门静脉、脾静脉内径（ＰＤ、ＳＤ）、门静脉血流速度及血流量（ＰＶ、ＰＱ．ＳＱ）较治疗前明显增加（Ｐ值＜０．０１），脾静脉血流速度（ＳＶ）明显减慢（Ｐ值＜０．０１）。结论：ＥＶＬ能短时间升高门静脉压，部分地加重ＰＨＧ和ＬＦ。     

THE FUNCTION OF THE PITUITARY-THYROIDAL AXIS IN ACROMEGALIC PATIENTS V. PATIENTS WITH HYPERPROLACTINAEMIA AND A PITUITARY TUMOUR

The function of the pituitary-thyroidal axis was examined in fifty-three of sixty-two patients with hyperprolactinaemia and a pituitary tumour and in forty of forty-four acromegalic patients, in whom one or more indices of the pituitary-thyroid function were determined before treatment. In the patients with hyperprolactinaemia and a pituitary tumour, sellar + extrasellar tissue (EST) size showed a significant negative correlation with the response of TSH to TRH (ΔTSH) as well as with the circulating T4 and T3 levels. These correlations were not present in the acromegalic patients. In the prolactinoma group a sharp decrease in mean serum T4 and T3 levels was found at sellar + EST sizes exceeding 3 cm². In twenty-three patients with a sellar + EST size of 3 cm² or more, thirteen (57%) showed a T4 level of less than 6 μg/dl against none of twenty-eight patients with a sellar + EST size of less than 3 cm². For T3, using a limit of 120 ng/dl, the corresponding numbers were eight out of thirteen (62%) and none of ten patients respectively. A positive correlation was observed between ΔTSH and the T3 levels but not between ΔTSH and T4, while in the acromegalic patients there was no correlation between TSH reserve and T3 or T4. In the patients with hyperprolactinaemia and a pituitary tumour positive correlations between basal TSH and ΔTSH as well as between T4 and T3 levels were observed. These correlations were not found in the acromegalic patients.
In conclusion: (1) Thyroid function appears to be independent of pituitary tumour size in patients with acromegaly but not in patients with hyperprolactinaemia and a pituitary tumour. (2) In acromegalic patients the high incidence of an impaired TSH response (without hypothyroidism and independent of tumour size) may be caused by suppression of TSH secretion rather than by destruction of thyrotrophic cells.     

哌唑嗪对单纯收缩期高血压患者左室肥厚的影响

以超声心动图观察哌唑嗪对48例单纯收缩期高血压(ISH)和32例舒张期高血压(DH)患者左室肥厚的影响。ISH组室间隔和左室后壁分别减少2.5和1.8mm(P均<0.01),左室重量指数下降61g/m~2(P<0.01),左心收缩和舒张功能改善。DH组室间隔肥厚减轻,但左室重量下降及左室舒张功能改善的幅度均小于ISH组。     

纳络酮对正常人和Cushing病患者血N-POMC和皮质醇对CRH反应的影响

作者观察了7例Cushing病患者和6例正常人血N-POMC和皮质醇对静脉注射CRH或CRH加纳络酮的反应。Cushing病患者对CRH的反应与正常人相似;而在加用大剂量纳络酮之后,却没有如正常人一样出现进一步增高反应。纳络酮在正常人可能通过阻断类阿片肽对内源性CRH的抑制作用而使反应进一步升高;在Cushing病患者可能存在着更强的CRH抑制因素,因而加用纳络酮不起作用。     

静脉注射纳络酮对正常人和垂体-肾上腺疾病患者ACTH和皮质醇分泌的影响

以血清N-POMC水平作为ACTH分泌的指标,观察了静脉注射大剂量(16mg)和小剂量(0.4mg)纳络酮(naloxone)对正常人和多种垂体-肾上腺疾病患者ACTH和皮质醇分泌的作用。在正常人注射大剂量纳络酮后30、60和90分钟时血清N-POMC和血浆皮质醇水平较生理盐水对照试验显著升高(P<0.02～0.001),但小剂量无效。Addison病和先天性肾上腺皮质增生症患者,注射大剂量纳络酮后,血清N-POMC的反应与正常人相似;小剂量也无此作用。但是,大、小剂量纳络酮均不能改变Cushing病或Nelson综合征患者血N-POMC和皮质醇水平。结果提示:纳络酮对于ACTH分泌的作用是通过了对其不敏感的δ-阿片肽受体起效的;Cushing病和Nelson综合征患者血ACTH分泌不受纳络酮的影响,可能是因为存在着自主或相对自主的垂体ACTH分泌瘤。     

硝酸甘油软膏与膜剂对冠心病患者左室功能的影响

硝酸甘油软膏与膜剂贴敷后对冠心病患者左室射血分数及相对心输出量较贴敷前或安慰剂有明显增加(P<0.001),其中以软膏作用为强,提示经皮肤吸收的硝酸甘油制剂可改善左心室功能。     

THE EFFECTS OF NAFARELIN AND DANAZOL ON VERTEBRAL TRABECULAR BONE MASS IN PATIENTS WITH ENDOMETRIOSIS

Single and dual-energy quantitative computed tomography (QCT) were used to measure spinal trabecular bone mineral content in 24 women treated with either nafarelin (15 patients) or danazol (nine patients) for endometriosis. Significant loss of bone mineral (-9.6 g/l; -5.9% P less than 0.001) was demonstrated after 6 months' treatment with nafarelin. This loss was reversible with no significant difference in the bone mineral measurement made before treatment and that made at 6 months after treatment was stopped (difference -1.95 g/l, NS). A small but statistically significant (+2.2 g/l, P less than 0.05) increase in bone mineral was measured in the group of patients treated with danazol for 6 months. The dual-energy QCT gave similar results, indicating little change in trabecular fat content. A significant correlation was demonstrated between mean serum oestradiol levels during treatment with nafarelin and the change in bone mineral (r = 0.655, P less than 0.005).     

促红细胞生成素改善慢性肾功能衰竭血透患者红细胞质量

目的：探讨重组促红细胞生成素（ｒＨｕＥＰＯ）替代治疗慢性肾功能衰竭（ＣＲＦ）贫血患者的红细胞质量改变。方法：选择４３例ＣＲＦ维持性血透贫血患者，２４例应用ｒＨｕＥＰＯ治疗，１９例应用输血治疗，分别观察两组治疗前、后，血红蛋白（Ｈｂ）、血球压积（Ｈｃｔ）、脂质过氧化物（ＬＰＯ）、超氧化物歧化酶（ＳＯＤ）和Ｎａ＾＋－Ｋ＾＋－ＡＴＰａｓｅ活性变化以及分析Ｎａ＾＋－Ｋ＾＋ＴＡＰａｓｅ活性与ＬＰＯ，ＳＯＤ之     

奥曲肽和垂体后叶素对门脉高压血流动力学的影响

应用９９ｍＴｃ－ＭＩＢＩ测定心／肝放射性摄取比值（Ｈ／Ｌ比值），脉冲多普勒超声检测门脉主干的血流量、血流流速及其内径，比较奥曲肽和垂体后叶素对肝硬化门脉高压患者的肝血流动力学的影响。结果示：二药对肝血流动力学改变可致门脉压降低，有利于破裂的食管曲张静脉凝血和止血。二药相比：Ｈ／Ｌ比值下降和门脉主干血流量减少亦有显著差异（分别为Ｐ＜０．０５和ｐ＜０．０１）。应用奥曲肽时未出现副作用，而应用垂体后叶素时１５例（４２％）出现短暂腹痛和排便感。本研究结果提示，奥曲肽对降低门脉血流及压力似较垂体后叶素为优，且无副作用。     

纳络酮对正常人和Cushing病患者胰岛素低血糖兴奋后ACTH分泌的影响

以血清N-POMC水平作为ACTH分泌的指标,观察了纳络酮(25mg)对5例正常人和5例Cushing病患者胰岛素低血糖兴奋后ACTH和皮质醇(F)分泌的影响,发现正常人胰岛素低血糖试验血N-POMC和F水平明显升高;加用类阿片肽受体阻滞剂纳络酮不能使胰岛素低血糖试验时血N-POMC和F的上升幅度进一步增加。推测这两种刺激兴奋CRH的途径相似,提示胰岛素低血糖试验可能涉及到类阿片肽机制。对Cushing病患者,无论是单纯胰岛素低血糖还是胰岛素低血糖加纳络酮均不能改变其血N-POMC和F水平,可能此两种刺激均未能引起内源性CRH释放增加。     

氟伐他汀对冠心病的微循环及血液流变学影响

目的研究氟伐他汀对冠心病的微循环及血液流变学影响,探讨其降脂以外的作用.方法观察154例冠心痛患者氟伐他汀治疗前后血脂及血液流变学、微循环的改变.结果氟伐他汀对冠心病血脂指标、血液流变学指标、微循环定量评分有明显影响(P＜0.05或P＜0.01).结论氟伐他汀能有效降低冠心病患者血脂水平,同时改善血液流变学异常及微循环障碍,有利于防止冠心病事件及血栓并发症的发生.     

胸腺肽对慢性乙肝患者血清细胞因子含量的影响

目的 观察大剂量国产胸腺肽对慢性活动性乙肝患者血清细胞因子的影响,探讨胸腺肽治疗慢性乙肝的机制。方法 选择慢性活动性乙肝患者３４例,分成两组：胸腺肽组１９例,一般护肝组１５例。比较观察治疗前后患者血清ＩＦＮ－α、ｓＩＬ－２ｒ、ＴＮＦ和β２－ＭＧ为指标的变化。结果 胸腺肽治疗后,患者ＰＢＭＣ ＩＦＮ－α诱生能力较治疗前上升１１９．９９％,血清ｓＩＬ－２ｒ和ＴＮＦ含量分别下降了３５．５６％和４１．８０     

吲达帕胺、卡托普利对高血压病患者尿白蛋白的影响

观察了４０例高血压病患者服吲达帕胺（ｉｎｄａｐａｍｉｄｅ）或卡托普利（ｃａｐｔｏｐｒｉｌ）８周前后尿液中白蛋白、血清肌酐及血尿素氮的变化。结果：两组降压效果相似，尿白蛋白均显著减少（Ｐ＜０．０１）；血清肌酐、白尿素氮无明显变化。结果表明，吲达帕胺、卡托普利均能减少尿白蛋白的排泄，对肾脏有保护作用。     

静脉注射地尔硫对室上性心动过速的即时疗效和电生理作用

本文通过食管程序电刺激,对20例阵发性室上性心动过速(简称室上速)患者,其中房室结内折返性心动过速(AVNRT)5例,房室折返性心动过速(AVRT)15例,研究静脉注射地尔硫或维拉帕米(0.2mg/kg)的即时疗效和电生理作用。结果表明:①两药均有明显抑制房室结传导作用,对旁路的传导无明显抑制;②对正常窦房结功能者无明显抑制作用;③单剂静脉注射时血压轻度降低,副作用轻;④终止诱发或自发性室上速的有效率分别为60%(地尔硫组)和80%(维拉帕米组)。