不同体位醛固酮/肾素比值对鉴别诊断原发性醛固酮增多症的意义

目的:研究不同体位醛固酮/肾素比值(ARR)对鉴别诊断原发性醛固酮增多症(PA)的两个主要亚型肾上腺皮质醛固酮瘤(APA)和特发性醛固酮增多症(IHA)的意义。方法:在40例临床确诊的PA患者中进行卧立位试验。结果:①IHA组立位醛固酮较卧位明显升高(P<0.05)②APA组立位较IHA组醛固酮及肾素都显著升高(P<0.05)③立位ARR≥100结合立位血浆醛固酮水平>200ng/dL鉴别APA及IHA敏感性和特异性分别为77.27%和78.26%。结论:立位ARR结合立位血醛固酮水平在APA及IHA鉴别诊断中价值有限。     

CLINICAL AND PATHOLOGICAL DIVERSITY OF PRIMARY ALDOSTERONISM, INCLUDING A NEW FAMILIAL VARIETY

1. Of 93 patients with primary aldosteronism seen during a 20 year period, 52 had an aldosterone-producing adenoma (APA) removed (five more await surgery), 14 had bilateral adrenal hyperplasia (BAH), three had glucocorticoid-suppressible hyperaldosteronism (GSH), one had adrenal carcinoma and 18 are yet to be categorized. 2. Seventy-three presented with hypertension and hypokalaemia. Others had markedly suppressed renal venous plasma renin activity (PRA) or elevated plasma aldosterone (PA)/PRA ratio, in new or resistant hypertensives. 3. The PA/PRA ratio was the most reliable screening test. 4. Diagnosis depended on the failure of suppression of aldosterone by salt loading and fludrocortisone. 5. Differentiation of BAH from APA depended on adrenal venous sampling comparing adrenal and peripheral venous PA/cortisol ratios. 6. A new familial variety of primary aldosteronism is described, with two affected members in each of three families. 7. Primary aldosteronism should be looked for in resistant and low-renin hypertension as well as in hypertension with hypokalaemia, and other family members should have PA/PRA measured if they are hypertensive.     

ALDOSTERONE REGULATION DURING SALINE INFUSION: USEFULNESS OF ALDOSTERONE/CORTISOL RATIO IN THE DIAGNOSIS OF ALDOSTERONE-PRODUCING ADENOMA

1. Saline infusion was performed in normal subjects, in essential hypertensives and in patients with aldosterone-producing adenoma (APA), with serial measurements of plasma aldosterone, cortisol and atrial natriuretic peptide (ANP). The effect of recumbency alone was also observed in the normal subjects. 2. Plasma aldosterone after saline infusion was less than 7 ng per 100 ml in the essential hypertensives and normal subjects, but greater than 9 ng per 100 ml in the patients with APA. 3. The aldosterone/cortisol ratio in normal subjects and in essential hypertensives was unchanged or fell during saline infusion, but rose in five of eight patients with APA. 4. Thus, an increase in aldosterone/cortisol ratio after saline infusion appears to be diagnostic of APA, but its absence does not exclude it.     

DISTINGUISHING ALDOSTERONE-PRODUCING ADENOMA FROM OTHER FORMS OF HYPERALDOSTERONISM AND LATERALIZING THE TUMOUR PRE-OPERATIVELY

In 14 hypertensive patients aldosterone/cortisol ratio was always lower in a peripheral vein or low IVC than in either adrenal vein. In four patients with a right-sided aldosterone-producing adenoma (APA), the aldosterone/cortisol ratio in peripheral vein was always higher than in the left adrenal vein. If only the left adrenal vein is cannulated, right-sided APA can still be diagnosed with certainty. In three patients with glucocorticoid-suppressible hyperaldosteronism, urinary excretion of both 18-oxocortisol and 18-hydroxycortisol was elevated. In four patients with APA excretion of 18-oxocortisol was elevated. In two of three patients with bilateral adrenal hyperplasia (BH), excretion of both steroids was normal. 75Se-selenomethylcholesterol scanning correctly lateralized five APA, but falsely lateralized a patient with BH. Results with CT scans were often misleading.     

ANGIOTENSIN-RESPONSIVEALDOSTERONE-PRODUCING ADENOMAS: POSTOPERATIVE DISAPPEARANCE OF ALDOSTERONE RESPONSE TO ANGIOTENSIN

1. Nineteen out of 47 patients (40%) with confirmed unilateral aldosterone-producing adenoma (APA) were responsive to low-dose angiotensin II infusion (AH-R), as defined by an increase in plasma aldosterone concentration of >50% over basal at 2 ng/kg per min for 60 min. 2. Seven to ten days after unilateral adrenalectomy, aldosterone was no longer responsive to angiotensin infusion in AII-R APA (100%, n = 17). Therefore, angiotensin responsiveness resides within the adenoma in AII-R APA. 3. The upright posture test for the differentiation of adenoma from hyperplasia was unreliable for the AII-R APA (26%), but generally reliable in the angiotensin-unresponsive subtype, (AH-U APA, 96%). 4. The reported predominance of females in APA was seen in AII-U APA (68%), but was reversed in AII-R APA (37%).     

RENIN GENE POLYMORPHISM ASSOCIATED WITH ALDOSTERONE RESPONSIVENESS TO THE RENINANGIOTENSIN SYSTEM IN PATIENTS WITH ALDOSTERONE-PRODUCING ADENOMAS

1. Aldosterone levels in patients with unilateral aldosterone-producing adenomas may be responsive or unresponsive to the renin-angiotensin system, with the former often previously misdiagnosed as bilateral adrenal hyperplasia. 2. In tumours from patients in the responsive subgroup, renin mRNA is expressed in greater amounts than in tumours from patients in the unresponsive subgroup, or in normal adrenals. 3. We compared the frequency of four renin gene polymorphisms in peripheral blood DNA from the two subgroups and found significant associations between BglI, TaqI and HinfI restriction fragment length polymorphisms (RFLP) and aldosterone responsiveness. 4. Allelic variation in the constitutive renin gene was associated with a specific cause of hypertension.     

海洛因依赖临床特征与μ阿片受体基因多态的关联

目的 :探讨 μ阿片受体 (OPRM1)基因多态与海洛因依赖及其临床特征的相关性。 方法 :采用病例对照设计 ,分别检测2 0 2名海洛因依赖患者和 187名正常对照OPRM1基因A118G位点和C17T位点多态 ,分析该多态性与海洛因依赖及其临床特征的相关性。结果 :未发现C17T位点的多态性 ;A118G位点多态在病例组和对照组间的差异无显著性 ;A118G位点多态与海洛因依赖患者的临床特征无显著性相关。结论 :OPRM1基因A118G位点多态与海洛因依赖无显著性相关。     

HIGH INCIDENCE OF PRIMARY ALDOSTERONISM IN 199 PATIENTS REFERRED WITH HYPERTENSION

1. This study sought to assess the incidence of primary aldosteronism in 199 hypertensives who were normokalaemic and in whom the question of primary aldosteronism had never been raised. 2. The screening test applied was the aldosterone to renin ratio in plasma, which was raised in 40 and normal in 159 patients. A second ratio was normal in 14 of these 40. 3. Twenty-two patients with two further raised ratios required fludrocortisone suppression testing. This has been completed in 17, and failure to suppress led to a diagnosis of primary aldosteronism in all. 4. A dexamethasone suppression test (DST) excluded ACTH-dependent hyperaldosteronism and laterality of aldosterone production was determined by adrenal vein sampling. 5. Unilaterality in five patients led to adrenalectomy in four and spironolactone in one. Bilaterality in six patients led to spironolactone. 6. This study so far provides a proven (minimum) incidence for primary aldosteronism of 8.5%, a probable incidence of 12.0% (including two raised ratios) and a possible (maximum) incidence of 13.0% (leaving out those with second ratio normal). Exclusion of hypokalaemic hypertensives will lead to an underestimation of the true incidence of primary aldosteronism. 7. Based on this and other evidence, it is estimated that the incidence of primary aldosteronism in the ‘essential hypertensive’ population is between 5 and 15%, and is probably around 10%.     

鹿类中药材的位点特异性PCR鉴定研究

目的　建立一种简便、准确的鹿类中药材鹿茸、鹿鞭、鹿筋、鹿胎的DNA分子标记鉴定方法。方法　在对鹿类中药材的正品原动物梅花鹿、马鹿及其混伪品原动物的Cytb基因全序列分析的基础上 ,设计了一对专用于鉴定正品鹿类药材的位点特异性鉴别引物ILu0 1 L和ILu0 1 H。结果　在 6 4℃的复性温度下 ,用鉴别引物对原动物样品进行鉴别PCR ,仅正品能得到约 36 5bp阳性扩增带 ;对鹿茸、鹿鞭及鹿筋正、伪品药材进行PCR鉴定 ,结果表明 :3批鹿茸仅一批为正品 ,2批鹿鞭皆为伪品 ,鹿筋正、伪品药材PCR鉴定与形态鉴定结果一致。随机选取 2枚鹿茸及一个原动物做Cytb基因片段序列分析 ,其结果与PCR鉴定完全一致。结论　对市售鹿类商品药材需加强质量监督和管理。所设计的鉴别引物对梅花鹿、马鹿有高度特异性 ,可应用于以其为原动物的鹿类中药材的鉴定。     

麦角生物碱生物合成研究进展

医用麦角生物碱 (ｅｒｇｏｔａｌｋａｌｏｉｄｓ)大多是由天然麦角生物碱经过结构改造而成 ,多具有重要的临床用途 ,少数天然麦角生物碱可直接作为药物。由于麦角生物碱类药物在临床应用上占有重要位置 ,加之麦角肽碱 (ｅｒｇｏｔｐｅｐｔｉｄｅａｌｋａｌｏｉｄｓ ,ｅｒｇｏｐｅｐｔｉｎｅｓ)有特殊的环肽结构 ,因此麦角生物碱生物合成的研究历来受到重视。近年来 ,现代生物技术和分子生物学方法进一步促进了麦角生物碱生物合成的研究。已基本弄清其生物合成途径 ,尤其是对一些关键酶的研究已有较大进展。1　麦角生物碱的生物合成途径麦角…     

STRUCTURE OF HUMAN RENIN AND EXPRESSION OF THE RENIN GENE

The amino acid sequence of human renin was identified for the first time. This was determined from the nucleotide sequence of exons in the human renin gene identified in a genomic library by recombinant DNA techniques. Examination of amino acid residues involved in the enzymatic hydrolysis by human renin of the unique Leu10-Val11 bond of human angiotensinogen revealed features peculiar to this highly specialized aspartyl protease. The expression of the renin gene was examined with a hybridization probe for renin mRNA in sections and extracts of tissues. In the submandibular gland of mice renin mRNA, like renin, increased during development and in response to testosterone in females; sodium depletion increased renin mRNA in kidney.     

ACCURATE DETERMINATION OF THE SIZE OF THE FIRST INTRON DELETION IN THE RENIN GENE OF SHR FROM AN AUSTRALIAN COLONY

1. It has been reported that the first intron of the renin gene of the spontaneously hypertensive rat (SHR) is shorter than that of the Wistar-Kyoto (WKY) rat, suggesting a role for this difference in the development of hypertension. 2. The genealogy of some Australian SHR colonies has raised doubts about its similarity to the Japanese, American and European colonies. 3. The polymerase chain reaction (PCR) technique has been used with primers identical to the flanking region of the first intron of the renin gene to determine its length in SHR, WKY and Sprague-Dawley (SD) from an Australian colony. 4. The size of the first intron of the renin gene in SHR, WKY and SD was found to be approximately 3870, 4550 and 5000 base pairs, respectively, results which agree with those previously published. 5. It was concluded that the first intron deletion, and its size, has been conserved in an Australian SHR colony.     

鹿类中药材的位点特异性PCR鉴定研究

目的　建立一种简便、准确的鹿类中药材鹿茸、鹿鞭、鹿筋、鹿胎的DNA分子标记鉴定方法。方法　在对鹿类中药材的正品原动物梅花鹿、马鹿及其混伪品原动物的Cyt b 基因全序列分析的基础上,设计了一对专用于鉴定正品鹿类药材的位点特异性鉴别引物ILu01-L和ILu01-H。结果　在6 4℃的复性温度下,用鉴别引物对原动物样品进行鉴别PCR ,仅正品能得到约365bp阳性扩增带;对鹿茸、鹿鞭及鹿筋正、伪品药材进行PCR鉴定,结果表明:3批鹿茸仅一批为正品,2批鹿鞭皆为伪品,鹿筋正、伪品药材PCR鉴定与形态鉴定结果一致。随机选取2枚鹿茸及一个原动物做Cyt b 基因片段序列分析,其结果与PCR鉴定完全一致。结论　对市售鹿类商品药材需加强质量监督和管理。所设计的鉴别引物对梅花鹿、马鹿有高度特异性,可应用于以其为原动物的鹿类中药材的鉴定。