甲状腺激素不敏感综合征诊疗综述

甲状腺激素不敏感综合征（thyroid hormone insensitivity syndrome,THIS）是机体靶器官、组织对甲状腺激素反应性降低的一类综合征,为罕见的常染色体显性或隐形遗传性疾病。研究发现该疾病与甲状腺激素受体β基因突变有关,由于基因突变程度不同导致临床表现复杂多样,临床上常常被误诊为Graves甲亢、甲减等常见甲状腺疾病,并因不恰当治疗造成病情加重。提高对THIS的认识、掌握规范的诊断方法和合理有效的治疗措施是广大临床医生避免误诊误治的根本。     

完全型雄激素不敏感综合征一家系基因诊断并文献复习

摘要：雄激素不敏感综合征（AIS）是由雄激素受体（AR）基因突变引起的罕见的X-连锁隐性遗传病,完全型雄激 素不敏感综合征（CAIS）是AIS中雄激素抵抗程度最严重的一种类型。本文对一个CAIS家系成员AR基因的二代测 序结果进行分析,发现先证者AR基因的第7外显子c.2566C>T发生突变,编码第856位精氨酸的密码子（CGC）改变 为半胱氨酸的密码子（TGC）,从而雄激素与AR受体结合受到影响,生物学效应不能有效发挥,临床表现为CAIS。经 Sanger测序验证,先证者妹妹和母亲也发现相同的突变。先证者和其妹妹为半合子突变,母亲为杂合突变。笔者认 为AR基因c.2566C>T（p.Arg856Cys）突变导致姐妹二人患CAIS,该突变遗传自她们的母亲。明确AR基因突变位点, 可为家系再次生育提供指导。     

Androgen insensitivity syndrome: a case report

This report refers to a rare case of complete androgen insensitivity syndrome that had presented at the age of 35 years with complaint of abdominal mass, primary amenorrhea and infertility to Jimma University Hospital. A well-developed breast with absence of axillary and pubic hair was seen on examination. There was also an abdominal mass arising from the pelvis occupying the hypogastric and right iliac region. Additionally, there was a reducible mass of 5 by 4 c.m at the left inguinal region. She had a normal female external genitalia with blindly ending vagina of about 4 c.m long. Laporotomy was done and a grayish white solid mass of 20 by 10 c.m. was found and removed. The reducible mass in the left inguinal canal was also removed surgically which was followed by herinorraphy. There were no ovaries or any other internal female genital organs identifiable. Histopathology of the tumor showed features of seminoma while the mass in the inguinal canal was consistent with testis. Literature review on diagnosis, differential diagnosis and management of androgen insensitivity syndrome was made and discussed. This is the first case report of androgen insensitivity syndrome (AIS) in an Ethiopian patient.     

Selective androgen insensitivity of hepatic drug-metabolizing enzymes in senescent mice

The normal sexual dimorphism in murine hepatic hexobarbital metabolism (i.e. females greater than males) was found to be absent in senescent animals. Hexobarbital metabolism, expressed as microsomal activity of hexobarbital hydroxylase and hexobarbital-induced sleep time, in senescent male mice was similar to that in females, but significantly greater than that found in young adult males. No age-related changes in hexobarbital metabolism were observed in intact females. In addition, experiments involving gonadectomies and testosterone administration indicated that both male and female senescent mice were insensitive to the normally repressive effects of androgens on hexobarbital hydroxylase. In contrast, the sexual dimorphism in the activity of p-nitrophenol UDP-glucuronosyltransferase was maintained in the senescent mice as well as the usual responsiveness to testosterone regulation. Furthermore, the growth-promoting effects of androgen on the kidneys and seminal vesicles were similarly expressed in young and old mice. Thus, our results suggest the development of an age-dependent and selective insensitivity of hexobarbital hydroxylase to androgenic regulation in the aging mouse.     

甲状旁腺激素不敏感综合征研究进展

甲状旁腺激素不敏感综合征是以甲状旁腺激素抵抗为主要特征的具有临床多样性、遗传异质性的疾病,是甲状旁腺功能减退症的一种特殊类型,又称为假性甲状旁腺功能减退症。本文针对PHP的发病及分子机制、PHP的分型及特点、临床表现、诊断及治疗等方面进行综述。     

4例肾病综合征利尿剂抵抗患者的药学监护

目的:探讨临床药师参与肾病综合征利尿剂抵抗患者用药调整的实践方式。方法:以利尿治疗为切入点,针对发生利尿剂抵抗的肾病综合征患者,开展药学监护,提出治疗方案调整建议。结果:临床药师为患者遴选合理的处理方案,个体化用药,成功缓解利尿剂抵抗患者症状。结论:临床药师结合药学知识与临床实践,参与到肾病综合征利尿剂抵抗患者治疗中,优化药物治疗方案,保证患者用药合理、安全、有效。     

从典型病例谈女性雄激素增多症的诊治

正常女性雄激素75%来自于卵巢,25%来自于肾上腺。女性体内具有生物活性的雄激素包括睾酮(T)、双氢睾酮(DHT)等水平升高或活性增强会导致女性雄激素增多症。其临床表现多样,皮肤的表现多为多毛、皮脂分泌增加或痤疮。当血中雄激素达一定水平时,则出     

成人多脾综合征的腹部CT表现

目的分析成人多脾综合征腹部CT影像特点,提高对多脾综合征的认识。方法回顾性分析4例多脾综合征的腹部CT表现。重点观察脾脏、胃、肝、胆囊、胰腺、肠管以及血管的位置和发育异常。同时回顾文献报道的15例成人多脾综合征的CT表现。结果本组4例患者均为CT检查偶然发现。男1例,女3例,脾脏数目2～12个,均沿胃大弯侧排列,其中1例位于右上腹;4例均存在短胰及肠旋转不良;3例肝段下腔静脉缺如,奇静脉异常连接并扩张;1例肝脏呈中间位;1例胆囊呈中间位并结石,1例胆囊左位。结论熟悉多脾综合征各种异常的CT表现,有助于准确诊断．减少漏误诊。     

Rubinstein-Taybi syndrome. Review of 732 cases and analysis of the typical traits

In 1963 Rubinstein and Taybi described a new syndrome characterized by broad thumbs and toes, facial abnormalities and mental retardation. The syndrome can be observed in the neonatal period by typical thumbs, halluces and facial abnormalities. The prevalence in the general population is unknown, however the disorder is not rare and is present in about 1:600 patients in mental retardation clinics. At the present time there is no definite inheritance pattern and recurrence is very unlikely. 18 different chromosomal anomalies have been identified in some patients with this syndrome. In this paper we identify a typical case and review the symptoms and signs of the RT syndrome and meta-analyze 732 cases.     

Thoracic empyema due to Streptococcus milleri: four cases

Four cases of Streptococcus milleri empyema occurring over a six month period are reported. Empyema was post-pneumonic in three patients and followed blunt abdominal and chest trauma in one patient. There was an absence of serious underlying disease in these patients and management consisted of tube drainage, lavage of the pleural space and prolonged intrapleural and systemically administered antibiotic therapy. Complete recovery was achieved in three patients and a satisfactory result in the other without surgical intervention. The clinical and microbiological features of this group of patients are reviewed.     

Primary bone marrow B-cell lymphoma: report of four cases

Bone marrow involvement is infrequent at presentation in cases of diffuse large B-cell lymphoma. We report four adult patients with diffuse large B-cell lymphoma in whom bone marrow involvement with hematologic manifestations was the predominant clinical feature at presentation. Three patients presented with a leukoerythroblastic blood picture and one with pancytopenia. In each case, the unusual hematologic manifestations, with bone marrow replacement and the presence of immature forms in the peripheral blood, led to consideration of alternative hematologic diagnoses, including acute granulocytic leukemia in three cases and a myelodysplastic syndrome in one. The correct diagnoses were established by immunohistochemistry on formalin-fixed, paraffin-embedded bone marrow for two cases and by flow cytometry on aspirated bone marrow or peripheral blood lymphocytes for the other two. Diffuse large B-cell lymphoma should be considered in the differential diagnosis of unusual hematologic presentations, particularly in the elderly.     

Review article: irritable bowel syndrome

Irritable bowel syndrome is a disease that can be diagnosed positively on the basis of an established series of criteria and limited exclusion of organic disease. It is the most common disease diagnosed by gastroenterologists and affects about 20% of all people at any one time. Symptoms fluctuate, and the overall prevalence rate is relatively constant in Western communities. Ten per cent of patients present to their physicians; the illness has a large economic impact on health-care utilization and absenteeism. Irritable bowel syndrome is a biopsychosocial disorder in which three major mechanisms interact: psychosocial factors; altered motility; and/or sensory function of the intestine. Management of patients is based on positive diagnosis of the symptom complex, limited exclusion of underlying organic disease and institution of a therapeutic trial. If patient symptoms are intractable, further investigations are needed to exclude significant motility or other disorders. Symptomatic treatment includes fibre for constipation, loperamide for diarrhoea and low-dose antidepressants or infrequent use of antispasmodics for pain; novel pharmacological agents, psychotherapy and hypnotherapy are being evaluated.     

阿斯综合征28例报告

阿斯综合征是心输出量突然减少,导致急性短暂性脑缺血而发生昏厥、抽搐、发绀等表现的一组病症。患此征者若不能获得及时正确地抢救则危及生命。我院于1992年1月～2000年10月共成功抢救阿斯综合征28例,现报告如下。1 临床资料1.1 一般资料 本组28例,男17例,女11例;年龄最小29岁,最大82岁,平均58.6岁。致阿斯综合征的病因:冠心病17例,其中急性心肌梗死13例,陈旧性心肌梗死与不稳定心绞痛各2例;Ⅲ度房室传导阻滞（Ⅲ度AVB）、病态窦房结综合征、急性病毒性心肌炎     

阿斯综合征28例报告

阿斯综合征是心输出量突然减少,导致急性短暂性脑缺血而发生昏厥、抽搐、发绀等表现的一组病症.患此征者若不能获得及时正确地抢救则危及生命.我院于1992年1月～2000年10月共成功抢救阿斯综合征28例,现报告如下.     

Hair to document drug-facilitated crimes: four cases involving bromazepam

The use of a drug to modify a person's behavior for criminal gain is not a recent phenomenon. However, the recent increase in reports of drug-facilitated crimes (sexual assault, so-called DFSA, robbery) has caused alarm in the general public. Drugs used can be difficult to detect (active products at low dosages, chemical instability), possess amnesic properties, and can be quickly cleared from body fluids. In case of long delay between the alleged crime and clinical examination, collection of blood or even urine can be of little value. This is the reason why this laboratory developed an original approach based on hair testing by liquid chromatography-tandem mass spectrometry. To explore the detectability of a single absorption of bromazepam in hair, two volunteers (male and female) received a 6-mg dose. A strand of hair was sampled about one month after exposure and was cut into three segments of 2-cm long. After pulverization, 20 mg of hair was incubated overnight in a phosphate buffer (pH 8.4). The aqueous phase was extracted with 5 mL of a mixture of diethyl ether/methylene chloride (80:20) in the presence of diazepam-d5, which was used as internal standard (IS). Hair extract was separated on a XTerra MS C18 column using a gradient of acetonitrile and formate buffer. Detection was based on two daughter ions: transitions m/z 316.0 to 182.2 and 209.3 and m/z 290.1 to 154.1 and 198.2 for bromazepam and the IS, respectively. In the hair of the two subjects, bromazepam was detected in the proximal segment at 0.8 and 4.7 pg/mg, respectively. Hair analysis was applied to four authentic criminal cases. In the two first cases, bromazepam tested positive in the corresponding hair segment at 5.7, and 10.3 pg/mg. In another case, head hair was sampled 19 weeks after the alleged offense, and its length (< 4 cm) did not allow analysis of the corresponding period. However, 4.1 pg/mg of bromazepam was quantified in the victim's pubic hair. In these three cases, concentrations were consistent with a single exposure to bromazepam. In the last case, bromazepam was detected at 15 pg/mg in the segment corresponding to the period of the alleged offence but also in the range 2 to 7 pg/mg in the four other consecutive segments, making a single exposure statement difficult.     

Distribution of methylone in four postmortem cases

Drugs derived from amphetamine, methamphetamine and their methylenedioxy- analogues, although being sold as plant food or bath salts, are being used as legal alternatives to scheduled amphetamine stimulants. These products often contain methylone, mephedrone and methylenedioxypyrovalerone (MDPV)--three amphetamine derivatives shown to have strong pharmacological effects. Four postmortem cases were analyzed for methylone, mephedrone and MDPV, with drug levels quantitated in multiple biological matrices. All four cases had detectable levels of methylone, with heart blood concentrations of 0.740, 0.118, 0.060 and 1.12 mg/L. Analysis of several tissue samples shows that methylone does not sequester in a particular tissue type after death. The average liver-to-blood ratio was 2.68. Two cases also had MDPV present, but insufficient data were collected to formulate a hypothesis on postmortem sequestration or redistribution. Two different extraction methods, as well as analysis of derivatized and underivatized methylone, show that the drug is suitable for analysis in either method. The cases are believed to show one instance of chronic methylone use, with a urine concentration of 38 mg/L.     

Review article: pharmacological treatment of hepatorenal syndrome

Hepatorenal syndrome (HRS) is a common complication of advanced cirrhosis characterized not only by renal failure but also by marked alterations in systemic haemodynamics and activity of endogenous vasoactive systems. Renal failure is due to a severe vasoconstriction of the renal circulation. The pathogenesis of HRS is not completely understood but it is probably the result of extreme underfilling of the arterial circulation secondary to arterial vasodilation located in the splanchnic circulation. As well as the renal circulation, all other extrasplanchnic vascular beds appear to be vasoconstricted. The diagnosis of HRS is currently based on the exclusion of nonfunctional causes of renal failure; prognosis of patients with HRS is very poor. Liver transplantation is the best option in selected patients, but it is not always applicable as survival expectancy is short. Vasoconstrictor drugs with preferential effect on the splanchnic circulation (vasopressin analogues with a predominant V1 receptor effect, such as terlipressin--Glypressin) are very effective in improving renal function, with reversal of HRS being achieved in approximately two-thirds of patients. There is no agreement as to the terlipressin treatment regimen that is associated with a greater efficacy and lower incidence of side-effects. It appears that the administration of albumin together with terlipressin improves the therapeutic response rate. The impact of treatment on the natural course of HRS remains to be assessed in prospective investigations, but it seems that the reversal of HRS is associated with improved survival. Finally, treatment of patients with HRS with terlipressin before transplantation seems to improve post-transplantation outcome.