Elevated plasma levels and platelet-associated expression of the pro-thrombotic and pro-inflammatory protein, TNFSF14 (LIGHT), in sickle cell disease

Chronic vascular inflammation and endothelial activation may initiate vaso‐occlusion in sickle cell disease (SCD). TNFSF14 (CD258; LIGHT), a recently‐identified pro‐thrombotic and pro‐inflammatory tumour necrosis factor (TNF)‐superfamily cytokine, has a potent activating effect on endothelial cells. We evaluated whether TNFSF14 production is altered in SCD and whether platelets contribute to this production. TNFSF14 was measured in platelet‐free plasma from healthy‐control individuals (CON), steady‐state sickle cell anaemia (SCA), SCA on hydroxycarbamide therapy (SCAHC) and haemoglobin SC (HbSC) patients. Mean plasma TNFSF14 was significantly increased in SCA, SCAHC and HbSC, compared to CON individuals. In SCA/SCAHC patients, plasma TNFSF14, showed no correlation with haematological variables, but was significantly correlated with serum lactate dehydrogenase and inflammatory markers (CD40LG , IL8 and ICAM1). Platelet‐membrane TNFSF14 expression was significantly augmented on SCA platelets, and correlated with platelet activation; furthermore, measurement of platelet TNFSF14 release indicated that platelets may be a major source of circulating TNFSF14 in SCA. Interestingly, high plasma TNFSF14 was significantly associated with elevated tricuspid regurgitant velocity (≥2·5 m/s) in a population of SCA/SCAHC patients. The pro‐inflammatory and atherogenic cytokine, TNFSF14, could contribute to endothelial activation and inflammation in SCA; future investigations may confirm whether this protein contributes to major clinical complications of the disease, such as pulmonary hypertension, and represents a potential therapeutic target.     

Ischemic stroke as the first manifestation of Wegener's granulomatosis

The most characteristic clinical manifestations of Wegener's granulomatosis are upper and lower respiratory tract and renal involvement. The central nervous system manifestations are uncommon and occur usually late in the course of the disease. We report a 48-year-old man who presented with an ischemic stroke as the first manifestation of Wegener's granulomatosis. Wegener's granulomatosis should be considered in the differential diagnosis of ischemic stroke even in the absence of extraneurological involvement.     

Thrombolytic therapy for central venous catheter occlusion

Background

Long-term central venous catheters have improved the quality of care for patients with chronic illnesses, but are complicated by obstructions which can result in delay of treatment or catheter removal.

Design and Methods

This paper reviews thrombolytic treatment for catheter obstruction. Literature from Medline searches using the terms “central venous catheter”, “central venous access device” OR “central venous line” associated with the terms “obstruction”, “occlusion” OR “thrombolytic” was reviewed. Efficacy of thrombolytic therapy, central venous catheter clearance rates and time to clearance were assessed.

Results

Alteplase, one of the current therapies, clears 52% of obstructed catheters within 30 min with 86% overall clearance (after 2 doses, when necessary). However, newer medications may have higher efficacy or shorter time to clearance. Reteplase cleared 67–74% within 30–40 min and 95% of catheters overall. Occlusions were resolved in 70 and 83% of patients with one and 2 doses of tenecteplase, respectively. Recombinant urokinase cleared 60% of catheters at 30 min and 73% overall. Alfimeprase demonstrated rapid catheter clearance with resolution in 40% of subjects within 5 min, 60% within 30 min, and 80% within 2 h. Additionally, urokinase prophylaxis decreased the incidence of catheter occlusions from 16–68% in the control group to 4–23% in the treatment group; in some studies, rates of catheter infections were also decreased in the urokinase group.

Conclusions

Thrombolytic agents successfully clear central venous catheter occlusions in most cases. Newer agents may act more rapidly and effectively than currently utilized therapies, but randomized studies with direct comparisons of these agents are needed to determine optimal management for catheter obstruction.     

Reduced habituation of the retinal ganglion cell response to sustained pattern stimulation in multiple sclerosis patients

ObjectiveSustained pattern stimulation in normal subjects induces adaptive changes in pattern electroretinogram (PERG), an effect that has been interpreted as a response of glial cells and retinal ganglion cells (RGC). The aim of this study was to compare the effect in normal subjects and in multiple sclerosis patients without previous optic neuritis.MethodsPERGs were elicited by a 7.5 Hz pattern stimulus, presented continuously over 152 s. Response cycles were averaged in 20 packets of 60 events each and amplitude and phase of the 2nd harmonic response was measured. Adaptive changes are expressed as amplitude reduction over the full examination time.ResultsIn normal subjects PERG amplitude declined progressively to a plateau (dA = ?0.46 μV, SE = 0.09 μV); in patients the effect size was severely reduced (dA = ?0.20 μV, SE = 0.04 μV). No significant difference was found in mean amplitude.ConclusionsThe results show reduced RGC habituation in patients, suggesting an abnormal gain and sensitivity control in the inner retina, even in absence of clinical optic neuritis. Recent findings in astrocyte biology and indications drawn from a mathematical model point to a key role of glial cells in this process.SignificanceThe proposed methodology may have implications in the assessment of MS patients and in understanding the pathophysiology of neurological and retinal disorders.     

内镜辅助下扩大额下入路到达颅底中央部的显微解剖

目的研究内镜辅助扩大额下人路到达颅底中央部的显微解剖及显露范围,为临床神经外科提供解剖学依据。方法测量20例干颅骨标本的骨性结构,用20例成人尸头湿性标本模拟扩大额下入路操作,使用内镜和显微镜观察并测量。结果扩大额下入路截除眶顶后能够使眉问到达颅底靶点之间的距离明显缩短（P〈0．05）,视角明显增加（P〈0．05）,利于术者操作,减少手术副损伤。内镜辅助下手术能够克服和避免单纯显微镜下操作颅底暴露的“死角”和不足。结论内镜辅助扩大额下入路能够较好地显露颅底中央部,熟悉颅底中央部的解剖结构有助于开展经扩大额下人路切除该部位巨大肿瘤的准确定位及术中安全操作,提高肿瘤的全切率。     

Growth and differentiation of neural stem cells in a three-dimensional collagen gel scaffold

Collagen protein is an ideal scaffold material for the transplantation of neural stem cells. In this study, rat neural stem cells were seeded into a three-dimensional collagen gel scaffold, with suspension cultured neural stem cells being used as a control group. Neural stem cells, which were cultured in medium containing epidermal growth factor and basic fibroblast growth factor, actively expanded and formed neurospheres in both culture groups. In serum-free medium conditions, the processes extended from neurospheres in the collagen gel group were much longer than those in the suspension culture group. Immunofluorescence staining showed that neurospheres cultured in collagen gels were stained positive for nestin and differentiated cells were stained positive for the neuronal marker βIII-tubulin, the astrocytic marker glial fibrillary acidic protein and the oligodendrocytic marker 2’,3’-cyclic nucleotide 3’-phosphodiesterase. Compared with neurospheres cultured in suspension, the differentiation potential of neural stem cells cultured in collagen gels increased, with the formation of neurons at an early stage. Our results show that the three-dimensional collagen gel culture system is superior to suspension culture in the proliferation, differentiation and process outgrowth of neural stem cells.     

Viscoelastic evaluation of fetal umbilical vein for reconstruction of middle cerebral artery

The transplantation of artificial blood vessels with 〈 6 mm inner diameter as substitutes for human arterioles or veins has not achieved satisfactory results. Umbilical vein has been substituted for ar- tery in vascular transplantation, but it remains unclear whether the stress relaxation and creep be- tween these vessels are consistent. In this study, we used the fetal umbilical vein and middle cere- bral artery from adult male cadavers to make specimens 15 mm in length, 0.196-0.268 mm in tu- nica media thickness, and 2.82-2.96 mm in outer diameter. The results demonstrated that the stress decrease at 7 200 seconds was similar between the middle cerebral artery and fetal umbilical vein specimens, regardless of initial stress of 18.7 kPa or 22.5 kPa. However, the strain increase at 7 200 seconds of fetal umbilical veins was larger than that of middle cerebral arteries. Moreover, the stress relaxation experiment showed that the stress decrease at 7 200 seconds of the fetal umbilical vein and middle cerebral artery specimens under 22.5 kPa initial stress was less than the decrease in these specimens under 18.7 kPa initial stress. These results indicate that the fetal umbilical vein has appropriate stress relaxation and creep properties for transplantation. These properties are advantageous for vascular reconstruction, indicating that the fetal umbilical vein can be transplanted to repair middle cerebral artery injury.