Malignant presacral ghrelinoma with long-standing hyperghrelinaemia

Abstract

Background. A 57-year old man with low-back pain was found to have a 3 × 3 × 3 cm presacral neuroendocrine tumour (NET) with widespread metastases, mainly to the skeleton. His neoplastic disease responded well to peptide receptor radionuclide therapy (PRRT) with the radiotagged somatostatin agonist ¹⁷⁷Lu-DOTATATE. During almost 10 years he was fit for a normal life. He succumbed to an intraspinal dissemination.

Procedures. A resection of the rectum, with a non-radical excision of the adjacent NET, was made. In addition to computerized tomography (CT), receptor positron emission tomography (PET) with ⁶⁸Ga-labelled somatostatin analogues was used.

Observations. The NET showed the growth pattern and immunoprofile of a G2 carcinoid. A majority cell population displayed immunoreactivity to ghrelin, exceptionally with co-immunoreactivity to motilin. Somatostatin receptor scintigraphy and ⁶⁸Ga-DOTATATE PET-CT demonstrated uptake in the metastatic lesions. High serum concentrations of total (desacyl-)ghrelin were found with fluctuations reflecting the severity of the symptoms. In contrast, the concentrations of active (acyl-)ghrelin were consistently low, as were those of chromogranin A (CgA).

Conclusions. Neoplastically transformed ghrelin cells can release large amounts of desacyl-ghrelin, evoking an array of non-specific clinical symptoms. Despite an early dissemination to the skeleton, a ghrelinoma can be compatible with longevity after adequate radiotherapy.     

Aggregation of mononuclear and red blood cells through an ��4��1-Lu/basal cell adhesion molecule interaction in sickle cell disease

Background

Abnormal interactions between red blood cells, leukocytes and endothelial cells play a critical role in the occurrence of the painful vaso-occlusive crises associated with sickle cell disease. We investigated the interaction between circulating leukocytes and red blood cells which could lead to aggregate formation, enhancing the incidence of vaso-occlusive crises.

Design and Methods

Blood samples from patients with sickle cell disease (n=25) and healthy subjects (n=5) were analyzed by imaging and classical flow cytometry after density gradient separation. The identity of the cells in the peripheral blood mononuclear cell layer was determined using antibodies directed specifically against white (anti-CD45) or red (anti-glycophorin A) blood cells.

Results

Aggregates between red blood cells and peripheral blood mononuclear cells were visualized in whole blood from patients with sickle cell disease. The aggregation rate was 10-fold higher in these patients than in control subjects. Both mature red blood cells and reticulocytes were involved in these aggregates through their interaction with mononuclear cells, mainly with monocytes. The size of the aggregates was variable, with one mononuclear cell binding to one, two or several red blood cells. Erythroid Lu/basal cell adhesion molecule and α₄β₁ integrin were involved in aggregate formation. The aggregation rate was lower in patients treated with hydroxycarbamide than in untreated patients.

Conclusions

Our study gives visual evidence of the existence of circulating red blood cell-peripheral blood mononuclear cell aggregates in patients with sickle cell disease and shows that these aggregates are decreased during hydroxycarbamide treatment. Our results strongly suggest that erythroid Lu/basal cell adhesion molecule proteins are implicated in these aggregates through their interaction with α₄β₁ integrin on peripheral blood mononuclear cells.     

路志正教授从脾胃辨治眩晕经验撷英

路志正教授认为,眩晕之本在于脾胃运化失司,痰、浊、瘀皆为其标,治疗当以调理中焦脾胃为中心,兼顾肝胆、升清降浊,临证多取温胆汤、半夏白术天麻汤、泽泻汤、清震汤等加减化裁。     

Single vial kit formulation of DOTATATE for preparation of 177Lu‐labeled therapeutic radiopharmaceutical at hospital radiopharmacy

The clinical applications of radiolabeled somatostatin analogue ¹⁷⁷Lu‐DOTA‐Tyr³‐Thr⁸‐Octreotide (¹⁷⁷Lu‐DOTATATE) constitute a promising treatment option for patients with disseminated and inoperable neuroendocrine (NET) tumors. Formulation of ¹⁷⁷Lu‐DOTATATE in hospital radiopharmacy under aseptic conditions in a safe and reliable manner is a major constraint for its extensive use. The present work was intended to develop a kit for the safe preparation of the therapeutic radiopharmaceutical, viz. ¹⁷⁷Lu‐DOTATATE of high quality that can be easily adapted at conventional hospital radiopharmacies. Single vial kits of DOTATATE were formulated and evaluated for suitability for radiolabeling as well as stability on its storage. Patient dose of ¹⁷⁷Lu‐DOTATATE (7.4 GBq) could be successfully prepared using semi‐automated in‐house setup that assures safe handling and high yields of product of pharmaceutical purity suitable for clinical use. Fast clearance of activity via renal route was observed in preclinical biodistribution studies of ¹⁷⁷Lu‐DOTATATE carried out in normal Swiss mice. Deployment of in‐house produced ¹⁷⁷LuCl₃, cold kits and easy adaptability of synthesis setup at hospital radiopharmacy for preparation is likely to expand applications of peptide receptor radionuclide therapy.     

东北梅花鹿的药用价值养殖优势与发展方向

梅花鹿全身都是宝,作为药用,首载于《神农本草经》,大量人工驯养梅花鹿,始自于300年前的清朝末年,东北梅花鹿具有较高的药用价值和经济价值,同时还具有很强的观赏性,开发与利用潜力极大。     

Current status and future of targeted peptide receptor radionuclide positron emission tomography imaging and therapy of gastroenteropancreatic-neuroendocrine tumors

Theranostics is the highly targeted molecular imaging and therapy of tumors. Targeted peptide receptor radionuclide therapy has taken the lead in demonstrating the safety and effectiveness of this molecular approach to treating cancers. Metastatic, well-differentiated gastroenteropancreatic neuroendocrine tumors may be most effectively imaged and treated with DOTATATE ligands. We review the current practice, safety, advantages, and limitations of DOTATATE based theranostics. Finally, we briefly describe the exciting new areas of development and future directions of gastroenteropancreatic neuroendocrine tumor theranostics.     

传为陆探微作《洛神赋图》弗利尔馆藏卷的探讨

现存《洛神赋图》尚有七种 ,今藏美国华盛顿弗利尔美术馆传为陆探微作的《洛神赋图》是其中唯一的白描本 ,而且首尾最为完备。该卷虽疑点较多 ,但将其与其他数种画迹及相关著录进行比较、考证 ,尚可看出其流传有序 ,所据母本依稀可辨。从该卷题跋也可以看出与唐人《洛神赋图》粉本的某些联系。由此可以推断唐人粉本、李公麟临本、《东图玄览》著录之白描绢本、传仇英仿本皆在明代社会流传。此卷系临仿唐人粉本或他本 ,故而命题为“唐陆探微九歌图” ,这是有可能的。如果此说成立的话 ,那么唐代是存在过题为陆探微所作《洛神图》的 ,此卷亦即唐本陆探微《洛神图》的再摹本。文中附图三幅均系国内外首次发表 ,弥足珍贵     

鲁迅思想与廉政文化建设简

当前的廉政文化建设中有两种不良倾向：一是满足于表面上的宣传,不能激发民众真正的参与热情,流于形式;一是陶醉于古代清官廉吏故事的讲述,难以与现实社会生活有效对接,疏于清谈。解决之道在于找到一种历史文化资源,既是全民族共同的文化记忆,又能够超越时代局限与当下社会语境产生共振。鲁迅思想便是其中典型的代表。鲁迅批判国民劣根性的思想,有助于我们深刻认识廉政文化建设的长期性、复杂性与艰巨性,克服急功近利观念与形式主义作风;鲁迅坚定的“立人”启蒙立场,尤其值得当代知识分子效仿,用以培育国民的公民意识与民主精神,真正实现廉政文化建设“以人为本”的根本目标;鲁迅的“韧性”战斗精神,是反腐败斗争取得胜利的有力武器,也是廉政文化建设取得实效的重要保障。继承鲁迅思想,发扬鲁迅精神,对当前的廉政文化建设将会起到积极推动作用。     

卢秉久教授配伍运用楮实子与枳椇子治疗酒精性肝病经验

[目的]总结卢秉久教授配伍运用楮实子与枳椇子治疗酒精性肝病的独到思想与经验方法。[方法]通过介绍祖国医学对酒精性肝病的认识和楮实子、枳椇子的功效特点,从验案两则出发,总结卢教授配伍运用楮实子与枳椇子治疗本病的学术思想与经验方法。[结果]本病系酒伤脾胃,致湿热内蕴,日久气血水相互搏结,终成正虚邪恋之势;楮实子滋肾清肝、助肾利尿;枳椇子利水消肿、善解酒毒,因此卢教授多配伍运用楮实子与枳椇子治疗本病。[结论]卢教授配伍运用楮实子与枳椇子治疗酒精性肝病疗效确切,值得学习借鉴与继承发扬。