Adrenocortical carcinoma -- improving patient care by establishing new structures.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and highly malignant tumour with a poor prognosis. Patients present with signs of steroid hormone excess (e.g., Cushing's syndrome) or symptoms due to an abdominal mass. DIAGNOSIS: In case of an adrenal mass, hormonal workup before surgery is required for differential diagnosis, perioperative management, and for follow-up. The imaging of choice is CT or MRI with MRI being of additional use when invasion of big vessels is suspected. Apart from that, the use of 18-FDG-PET is becoming increasingly established. TREATMENT: Surgical resection is the therapeutic option of choice in stages 1 - 3. In stage 4, the adrenolytic compound mitotane is part of the first-line treatment, but often needs to be combined with cytotoxic chemotherapy. Most patients will eventually have a recurrence, so adjuvant treatment (mitotane/tumour bed radiation) has to be considered in high risk patients, even if randomized controlled trials on adjuvant treatment are still lacking. STRUCTURAL PROGRESS: Several national and European structures have recently been established in order to increase our knowledge of ACC, improve therapeutic options and diagnostic procedures, and promote research. GANIMED, as a Germany-wide network of experts on adrenal diseases, has been founded allowing for improved gathering of data and joint studies. ENSAT (European Network for the Study of Adrenal Tumours) has been brought to life, aiming at European standards for therapy, diagnosis and tumour banking. Since 2003, patients can be enrolled in the German ACC Registry. France and Italy have also developed a central registry to collect nationwide data from patients with ACC. For the first time, patients with metastatic/unresectable ACC can participate in a prospective controlled randomized trial comparing two different cytotoxic chemotherapy regimes (FIRM-ACT).     

An update on the overnight dexamethasone suppression test for the diagnosis of Cushing's syndrome: limitations in patients with mild and/or episodic hypercortisolism.

The overnight one-mg dexamethasone suppression test has been used for many years to screen for Cushing's syndrome. This test has usually been evaluated in controls versus patients with severe hypercortisolism. Under these conditions, the overnight dexamethasone suppression test has been reported to have high sensitivity and specificity. The objective of this study was to determine the sensitivity of the one mg overnight dexamethasone suppression test in patients with mild and/or periodic Cushing's syndrome. Therefore, an overnight dexamethasone suppression test was performed in 17 consecutive patients presenting to an endocrinology clinic with signs and symptoms of hypercortisolemia who were later proven to have Cushing's syndrome. The majority of patients were found to have both mild and periodic hypercortisolism. One mg of dexamethasone was given at midnight and a plasma cortisol was measured by radioimmunoassay at 08:00 the following morning. Using a cut-off for a morning cortisol following overnight dexamethasone of > 5 microg/dL, only three of 17 patients failed to suppress to a value less than this cut-off (sensitivity 18 %). A cut-off of > 2 microg/dL gave similar sensitivity. Even with a stringent cut-off point of > 1.8 microg/dL, only seven of 17 patients failed to suppress to a value less than this cut-off point (sensitivity of 41 %). These results demonstrate that the great majority of patients with mild and/or periodic Cushing's syndrome suppress to overnight dexamethasone. Since patients with mild and/or periodic Cushing's syndrome are the patients in whom the identification of hypercortisolism is difficult, our results from this relatively small study suggest that this test should no longer be used to exclude these patients from further workup for Cushing's syndrome.     

Radioiodine therapy of Graves' hyperthyroidism in patients without pre-existing ophthalmopathy: can glucocorticoids prevent the development of new ophthalmopathy?

BACKGROUND: Radioiodine therapy (RIT) combined with glucocorticoids is an effective therapy for Graves' disease, but it is debatable whether glucocorticoids should be applied in patients without Graves' ophthalmopathy (GO). METHODS: The effect of 0.4 - 0.5 mg prednisone every second day over a period of 5 weeks after RIT was monitored over a follow-up period of at least 12 months after RIT. A questionnaire was sent to 186 consecutive patients without GO concerning eye symptoms after RIT. 148 patients (80 %) answered. If eye symptoms had occurred after RIT, additional clinical examination was carried out at our outpatient clinic. The primary endpoint was the absence or onset of GO within the first year after RIT. RESULTS: Within 12 months after RIT the examination confirmed GO in 5 out of 148 patients (3.4 %). In all cases the symptoms were transient. No adverse reaction to the use of prednisone after RIT was noted. CONCLUSIONS: The risk of new GO in the first year after RIT was low and the clinical course of GO was mild when RIT was combined with a low-dose glucocorticoid regimen. Preventive administration of glucocorticoids can therefore be recommended in patients with Graves' disease even without evident GO.     

Role of tumour necrosis factor-alpha receptor p75 in cigarette smoke-induced pulmonary inflammation and emphysema.

Chronic obstructive pulmonary disease (COPD) is characterised by a local pulmonary inflammatory response to respiratory pollutants and by systemic inflammation. Tumour necrosis factor (TNF)-alpha has been implicated in systemic effects of COPD and operates by binding the p55 (R1) and p75 (R2) TNF-alpha receptors. To investigate the contribution of each TNF-alpha receptor in the pathogenesis of COPD, the present study examined the effects of chronic air or cigarette smoke (CS) exposure in TNF-alpha R1 knockout (KO) mice, TNF-alpha R2 KO mice and wild type (WT) mice. CS was found to significantly increase the protein levels of soluble TNF-alpha R1 (by four-fold) and TNF-alpha R2 (by 10-fold) in the bronchoalveolar lavage of WT mice. After 3 months, CS induced a prominent pulmonary inflammatory cell influx in WT and TNF-alpha R1 KO mice. In TNF-alpha R2 KO mice, CS-induced pulmonary inflammation was clearly attenuated. After 6 months, no emphysema was observed in CS-exposed TNF-alpha R2 KO mice in contrast to WT and TNF-alpha R1 KO mice. CS-exposed WT and TNF-alpha R1 KO mice failed to gain weight, whereas the body mass of TNF-alpha R2 KO mice was not affected. These current findings suggest that both tumour necrosis factor-alpha receptors contribute to the pathogenesis of chronic obstructive pulmonary disease, but tumour necrosis factor-alpha receptor-2 is the most active receptor in the development of inflammation, emphysema and systemic weight loss in this murine model of chronic obstructive pulmonary disease.     

10对联体双胎分离术后的远期结果

背景／目的：从1978-2000年，有10对联体双胞胎成功接受了手术分离，结果14人存活。其中6对是因为他们的联体同胞死亡或濒临死亡而接受紧急分离手术。剩余的4对，每对至少一个同胞接受至少一次的急诊手术后，才接受联体分离手术。方法：对这一独特的队列进行包含6个项目的问卷调查。问题的设计是开放式的，为父母／家庭提供有关信息的最大机会。对每个家庭就相同的问题也进行了当面的问卷调查。医师询问了与身体健康和疾病相关的一些问题。而社会工作询问了与发育、教育、社会心理和家庭功能相关的问题。结果：前面提及的14人存活的双胞胎中，4人大学毕业，1人于1981年完成中学学业，剩余9人正在上学。14人在最初的手术后，还需要接受再次手术，尤其是需要矫正泌尿系统、畸形、神经外科和小儿外科的问题。结论：通过超声检查对联体双胎进行宫内诊断，可以使医师和胎儿父母在孕早期决定在终止妊娠时是进行双胎分离还是保全其中一个。这些病例报道通过描述14例手术存活的长期体格检查和心理学检查结果，为医师和父母在关键时刻做出决定提供了另外有助的依据。     

The need for a revival of psychoanalytic investigations into premature ejaculation

Although psychoanalysis was the first-choice treatment for premature ejaculation (PE) between 1920 and 1960, hardly any reports on its efficacy have been published. Moreover, a scientific debate about its findings has never been fully developed. The recent progress that has been made in the classification of three different PE syndromes creates a new opportunity for psychoanalytic investigations of men with complaints of PE, distinguished by the actual duration of their intravaginal ejaculation latency time (IELT). The term premature-like ejaculatory dysfunction has been introduced to distinguish men with self-perceived PE at normal and long IELT durations from those men with lifelong, acquired and normal variable PE. Psychoanalytic research may contribute to a better understanding of the consequences of objective early ejaculations on the unconscious mental life of men with the four forms of PE. By integrating neurobiological, clinical and epidemiological data of ejaculatory performance, a revival of psychoanalytic research of PE in the four distinct, classified PE groups, will probably contribute to a deeper insight in to the unconscious mental life of men affected by PE.     

复合杂合parkin基因突变家族的不同表型

背景：Parkin基因（PRKN）突变可导致常染色体隐性遗传性早发帕金森病（EOPD）。目的：探讨EOPD白人家族PRKN突变的表现和基因型-表型关系。设计：对EOPD家族的3代20例成员进行基因分析，该家族有4例患者。应用直接基因组DNA测序、半定量聚合酶链反应、实时定量聚合酶链反应以及逆转录酶聚合酶链反应分析以确定PRKN突变。结果：4例早发患者（年龄30—38岁）被确定有PRKN复合杂合突变（T240M和EX5_6缺失），虽然PRKN的杂合T240M和纯合EX5_6缺失突变已有描述，但是据悉，本文为上述复合杂合突变的首次报道。患者的表型为典型常染色体隐性遗传性EOPD的表现，其特征是对左旋多巴治疗有效、相对缓慢的进展和运动障碍。所有杂合突变的基因携带者（T240M或EX5_6缺失）和1例56岁的复合杂合突变女性携带者（T240M和EX5_6缺失）无任何神经系统症状。结论：研究发现，PRKN基因复合杂合突变（T240M和EX5_6缺失）导致一个大的白人家族中4例成员发生常染色体隐性遗传性EOPD。另外1例成员具有相同的突变，比4例患者的平均发病年龄大10岁，并且无本病的临床表现。不完全的外显率对遗传咨询具有暗示作用，并且提示复杂的基因一环境交互作用在PRKN相关EOPD的发病机制中发挥作用。     

Case Report: Second case of a successful pregnancy in maternal isovaleric acidaemia

Summary: A female patient with isovaleric acidaemia had a successful outcome from pregnancy.     

Denervation pattern of three mimic muscles in Bell's palsy.

OBJECTIVE: To explore the presence and grade of denervation in three mimic muscles in facial nerve palsy. METHODS: The frontalis, orbicularis oculi (OO), and mentalis muscles were explored in 54 patients with Bell's palsy, after 30 days from the beginning of symptoms. Concentric needle electromyography, including fibrillation detection, was performed in the three muscles on the affected side. Compound muscle action potentials (CMAP) were recorded on both sides and a CMAP ratio was calculated from each muscle. The House-Brackman scale was used to assess the initial clinical evaluation and the follow-up until recovery. RESULTS: Fibrillation was recorded in 32 patients on the 30th day after the onset and was present in 100% of mentalis and in 90% of frontalis, but in only 34% of OO, a statistically significant difference. The grade of fibrillation in OO was also statistically lower from those in the other two muscles. The 32 patients were grouped according to the presence (A) or not (B) of fibrillation in OO. In group A, CMAP ratios (affected/normal side) did not differ significantly among the three muscles. However, in group B they were significantly greater in OO and frontalis than in mentalis. In between-group comparison, group B muscles had significantly higher CMAP ratios, lower degree of fibrillation, and better functional recovery. CONCLUSION: In facial palsy, the presence and grade of fibrillation in OO are lower than in frontalis and mentalis muscles and prognosis is more favorable for the non-fibrillating OO group of patients.     

27-jähriger Reiserückkehrer mit hohem Fieber und septischem Schock im Verlauf

A 27-year-old man was admitted with high fever and shivers eleven days after returning from vacation in Indonesia. Physical examination, laboratory values, abdominal ultrasound, and chest x-ray were not conclusive. All blood cultures yielded growth of Salmonella enterica serovar Typhi, and typhoid fever was diagnosed. Subsequently, the patient developed septic shock and pulmonary edema.In this case report epidemiological, clinical, and therapeutic aspects of typhoid fever are discussed with special emphasis on criteria for severe typhoid fever, which is treated with additional glucocorticoids.