Vitreous humour as a complementary sample to blood for the detection/confirmation of diazepam: ante-mortem and post-mortem studies in an animal model

The quantification of medical or toxic substances in vitreous humour (VH) could be very useful in forensic toxicology when blood sample determinations are impossible due to absence or deterioration. However, few studies have been made in this area and even fewer have tried to find a relationship between drug levels in both samples. To determine a correlation ratio between blood and VH diazepam (DZ) levels, we performed an experimental study using rabbits administered with a sub-toxic dose of DZ under known and controlled conditions. Blood and VH samples were collected 0.5, 1, 2, 3 and 6 hours after the drug administration in order to determine DZ and its main active metabolite, desmethyldiazepam (DMD). In addition, we have studied an animal group sacrificed 2 hours after intramuscular (i.m.) drug administration with blood and VH collection 24 hours later, to evaluate the existence of possible post-mortem changes. After DZ administration, a fast absorption phase was observed with a plasma Cmax value 1 hour after, followed by a rapid concentration decrease, with a half-life of 1 hour, indicating that, besides elimination, a fast distribution to other organs and tissues and/or hepatic metabolism occurred. Diazepam Cmax value in VH was achieved between 1 and 2 hours, when plasma concentrations had already decreased to half the value. The plasma/VH DZ ratio calculated at this time was 10. In the post-mortem study, while plasma DZ concentration at 24 hours was smaller, DMD levels were higher than those at the time of death. In the VH, both DZ and DMD concentrations at 24 hours were higher than those obtained at the time of death. That is, in both fluids DZ and DMD concentrations were different from those at the time of death and post-mortem distribution and redistribution phenomena occurred. The combination of ante-mortem and post-mortem studies has allowed the determination of a correlation ratio for DZ in the rabbit of 6 x, comparing the concentrations in VH collected 24 hours after death with the concentrations detected in plasma at the time of death. This study opens new perspectives for the use of VH as a complementary sample to blood for DZ detection and confirmation. The putative relevance of the correlation ratio obtained, for forensic toxicology practice with medical substances, namely benzodiazepines, recommends further studies in humans.     

Effects of nadroparin on bone histomorphometric parameters in rats

Nadroparin calcium is a low-molecular-weight heparin. Low-molecular-weight heparins have a number of advantages over standard heparin (heparin), but it is not clear if low-molecular-weight heparins have less effect on bones than heparin. Administration of heparin can lead to osteoporosis. The aim of the present study was to investigate the effects of nadroparin on the rat osseous system and compare them with those of heparin. The experiments were carried out on female Wistar rats (13-15 weeks old at the beginning of the experiment), divided into 5 groups: I. Control, II. Nadroparin (1000 anti-Xa IU/kg s.c. daily), III. Nadroparin (2000 anti-Xa IU/kg s.c. daily), IV. Heparin (1000 IU/kg s.c. daily), V. Heparin (2000 IU/kg s.c. daily). Nadroparin and heparin were administered for 4 weeks. Bone mass, mineral and calcium content, macrometric and histomorphometric parameters (endosteal and periosteal transverse growth, width of endosteal and periosteal osteoid, transverse cross-section area of the cortical bone in the diaphysis and of the marrow cavity in the tibia, width of epiphyseal cartilage, width of trabeculae in the epiphysis and metaphysis in the femur) were examined. The effect of heparin on the ratio of bone mineral content to bone mass was more pronounced than that of nadroparin. Nadroparin caused unfavorable changes in the investigated bone histomorphometric parameters, similar to those caused by heparin. Nadroparin and heparin caused disorder of bone formation and intensification of bone resorption in rats.     

丙泊酚靶控输注用于儿童鼾症鼻内镜手术

目的评价丙泊酚靶控输注在儿童鼻内镜手术中对血压、心率、术野出血及术后苏醒过程的影响。方法86例因腺样体肥大拟行手术患儿,ASA为Ⅰ-Ⅱ级,随机分成二组,每组43例,B组行丙泊酚靶控输注麻醉,I组行异氟醚吸入麻醉。分别观察手术开始后10,25,45 m in血压、心率变化及术野质量评分,记录术毕患儿自主呼吸恢复时间、睁眼时间、拔管时间,观察术后恶心、呕吐、躁动的发生率。结果①两组收缩压、舒张压和术野质量评分无显著差异;②B组患儿术后自主呼吸恢复时间、睁眼时间、拔管时间显著短于I组;③I组并发症高于B组。结论丙泊酚靶控输注用于儿童鼻内镜手术,血压、心率、术野质量评分佳,术毕麻醉恢复更为迅速、优良。     

Langerhans' cell histiocytosis: various manifestations with the same histopathologic base

Langerhans' cell histiocytosis (LCH), previously known as histiocytosis X, is a rare disease. It is characterized by the accumulation and proliferation of histiocytes, eosinophils and Langerhans' cells with Birbeck granules detected by electron microscopy. It involves single organs or systems or can present as a multisystem disease. The clinical presentation may vary widely, ranging from benign self-limiting types with spontaneous regression to slowly-progressive malignant disease. We report five cases of LCH with the same histopathologic basis but different outcome.     

External ventricular assist devices as circulatory support in patients with dilated cardiomyopathy

Ventricular assist devices have demonstrated their utility in patients with intractable cardiac failure, both as support until complete myocardial recovery and as a bridge to transplantation. Specific pediatric pneumatic paracorporeal systems can be applied even in infants. Long-term survival has been reported although experience is limited. We report the case of an 8-year-old boy with dilated cardiomyopathy awaiting cardiac transplantation. The patient developed profound cardiogenic shock with multiorgan failure while being evaluated for heart transplantation. He was given biventricular assistance with the MEDOS-HIA system (MEDOS-Helmholtz Institute). Maximum stroke volume ventricles of 25 and 22 ml were used, achieving a cardiac output of 2.2 l/min in both ventricles. The patient was supported with ventricular assistance for 9 days, but multiple organ failed to improve and transplantation became impossible. Progressive loss of peripheral circulatory resistance unresponsive to treatment developed and ventricular assistance was discontinued. The previous severe shock and advanced and progressive multiorgan failure could be responsible for the poor outcome of our patient despite maintenance of adequate cardiac output. Nevertheless, the use of ventricular assist devices is a real therapeutic alternative in children with severe cardiogenic shock, allowing them to recover completely or undergo heart transplantation. Patient selection, the choice of a system of appropriate size, and early implantation seem to be the cornerstones for obtaining good results.