部分脱乙酰甲壳质生物套管小间隙桥接修复周围神经损伤:免疫组织化学观察

目的:神经断端保留小间隙的静脉桥接模拟神经外膜形成神经再生室,为周围神经再生创造了良好的生理环境,从而保证神经束的良好对合。实验采用部分脱乙酰甲壳质作为套管材料,用小间隙桥接方法修复坐骨神经损伤,观察套管内的神经再生情况,并与传统外膜缝合法进行比较。方法:实验于2001-01/2002-10在北京大学人民医院创伤骨科实验室完成。①主要材料:实验所用中空圆柱形套管为北京大学人民医院与中国纺织科学院共同发明的一种部分脱乙酰甲壳质生物套管(专利号:01136314.2)。实验中所用套管尺寸为:管长4 mm,壁厚0.1 mm,内径1.5 mm。②实验动物:健康成年雄性SD大鼠20只,随机分成2大组,每组10只,每一大组全部10只动物的左腿坐骨神经为一组,右腿坐骨神经为另一组,每组10根坐骨神经。另取5只同样大鼠双侧坐骨神经未做处理作为正常对照组。③实验方法:外膜原位缝合组:切断坐骨神经,显微镜下神经外膜原位缝合;生物套管小间隙原位桥接组:切断坐骨神经,显微镜下小间隙套管桥接;断端旋转180°外膜缝合组:切断坐骨神经,显微镜下远端旋转180°后,神经外膜缝合;断端旋转180°生物套管小间隙桥接组:切断坐骨神经,显微镜下远端旋转180°后,小间隙套管桥接。④实验评估:术后第7,14,21,28,42天取坐骨神经,进行免疫组织化学染色及观察。结果:再生神经延套管中央走行,7 d时已有部分纤维通过2 mm间隙,14 d时有髓纤维数量明显多于近端。21 d后,套管组与原位外膜组新生有髓神经纤维数相近。再生纤维胞核数量较多,髓鞘纤细。套管结构完整。结论:此种部分脱乙酰甲壳质生物套管内的再生神经连续、整齐,髓鞘完整,其神经再生情况好于传统外膜缝合法。     

Plasma cortisol is often decreased in patients treated in an intensive care unit

Objective: To investigate the prevalence of adrenal hypofunction, as assessed by plasma cortisol (p-cortisol) and its relationship to clinical events. Design: Prospective, consecutive. Setting: General intensive care unit in a university hospital. Patients: Fifty-five patients (34 men and 21 women) were studied (surgery 40 patients, hemodialysis 5, ventilator treatment 45, sepsis 21). Methods: Morning basal levels of p-cortisol were determined. Previous reports define adrenal insufficiency to be present if p-cortisol under stressful conditions is lower than either 400 or 500 nmol/l. The tetracosactoid test (250 μg Synacthen) was performed in 16 patients and urinary 24-h excretion of cortisol in 24 (none on corticosteroid treatment). Results: Median p-cortisol was 550 nmol/l (range 20–1764). In 36 % of patients p-cortisol was lower than 400 nmol/l and in 47 % lower than 500 nmol/l. There was a significantly increased probability (P < 0.05) of p-cortisol being below 400 nmol/l in patients admitted due to trauma or cerebral disorder and in patients on ventilator therapy or on mannitol. Thirty minutes after tetracosactoid administration p-cortisol response was lower than 200 nmol/l in 56 % of the patients. Conclusions: Several patients had low p-cortisol and attenuated responses to tetracosactoid, indicative of adrenal insufficiency. There seem to be certain risk factors for adrenal hypofunction which may justify more frequent use of physiological doses of corticosteroid in selected patients Received: 5 February 1999 Final revision received: 16 December 1999 Accepted: 21 December 1999     

Therapeutic apheresis in Sweden: update of epidemiology and adverse events.

The indications of apheresis have changed over time due to results from various studies as well as the innovation of new techniques and ideas. To get an overview of the indications used for apheresis by colleagues elsewhere, data from registries are valuable. In addition, registries can be used for detection of severe adverse events as well as extent of adverse events in various types of treatment. To have a basis for statistical calculations, apheresis units need to be very large or centralisation of data needs to be performed. Data from more than 20000 procedures show that in about 4.3% of occasions adverse events and other problems will develop. Interruption of the procedure was done in 1%, most frequently a plasma exchange. Technical problems can be expected more frequent when performing LDL apheresis and immunoadsorption. Severe adverse events needing medication or interruption of the treatment, such as hypotension and arrhythmia, will develop in about 1% of the procedures. Such an episode occurs more often in patients with TTP/HUS and Guillain-Barré syndrome than in hypercholesterolemia, hyperviscosity syndrome or septic shock/MODS. The non-severe adverse events have increased over time. The results will provide focus in analyses for the reduction of such adverse events.     

Plasma exchange as rescue therapy in multiple organ failure including acute renal failure

OBJECTIVE: To describe the outcome of using a rescue therapy including plasma exchange given to patients with a progressive acute disseminated intravascular coagulation and multiple organ dysfunction syndrome. STUDY DESIGN: Retrospective study. SETTING: University and county hospital. PATIENTS: Included were 76 consecutive patients (41 men and 35 women) treated with plasma exchange as rescue therapy besides optimal conventional therapy during a progressive course of disseminated intravascular coagulation and multiple organ dysfunction syndrome, including acute renal failure. Of the 76 patients, 66% needed dialysis. The distribution was hemodialysis in 76%, continuous arteriovenous hemofiltration in 36%, continuous venovenous hemodialysis in 12%, and peritoneal dialysis in 24%. The median organ-failure score was 5 (range, 1-6). Seventy-two percent required mechanical ventilation; septic shock was present in 88%. The median septic shock score was 4 (range, 2-4). Nine patients had another reason than sepsis for the multiple organ dysfunction syndrome. INTERVENTION: Plasma exchange (centrifugation technique) was performed until disseminated intravascular coagulation was reversed (median, two times; range, 1-14). Besides antibiotics and fluid administration, most patients received heparin or low molecular weight heparin (77%), steroids (87%), and inotropes (88%). More than one vasoactive drug was used in 57% of the patients. MEASUREMENTS AND MAIN RESULTS: Eighty-two percent of the patients survived and could leave the hospital. The previously observed survival rates by others for this category of patients would be <20%, and thus, the outcome in this study is significantly better. CONCLUSION: Plasma exchange using plasma as replacement may, in addition to conventional intensive care, help to reverse severe progressive disseminated intravascular coagulation and multiple organ dysfunction syndrome and improve survival.     

In face of the increasing efficacy of lipid-lowering therapy, is there still a place for LDL-apheresis?

Based on a large body of evidence, high LDL-cholesterol concentrations in blood is a key factor of coronary heart disease (CHD). Overall, the observational studies show a curvilinear relationship between blood cholesterol level and coronary heart disease risk. Even more relevant are the randomised trials, firmly establishing that within just a few years a cholesterol-lowering therapy confers a dramatic effect on cardiovascular morbidity and mortality. More recent studies indicate that there is a greater risk reduction in those subjects achieving lower low-density lipoprotein cholesterol (LDL-C) levels--i.e. lower is better. While this favours aggressive therapy, it is nevertheless imperative to precise patients selection for every therapy that entails a major commitment for the patient and medical community. Therefore, well-defined criteria for use of LDL-apheresis have yet to be established in the light of the expanding therapeutic armamentarium. Based on the current knowledge of the impact of statin therapy and anticipating that new options will further optimize the management of dyslipidemia in high-risk patients, we propose a reliable assessment of the effects of LDL-apheresis.     

Analyses of data of patients with Thrombotic Microangiopathy in the WAA registry

Thrombotic Microangiopathy (TMA) is a histopathological feature of various diseases including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome.The aim of this study was to investigate the outcome and prognostic variables of TMA-patients.

Materials and methods

Data were consecutively retrieved from the WAA-apheresis registry (www.waa-registry.org) during 2003–2009. Included were all 120 patients (1237 procedures) who suffered from various forms of TMA, as registered by the ICD-10 code M31.1. Besides registry data, more extensive information was retrieved from the latest 64 patients. Adverse events of the TMA patients were compared to those of the other patients in the registry.

Results

The mean age was 46 years (range 11–85 years, 57% women). In 72% therapeutic apheresis was due to an acute indication while a long-term indication was present in 28%. Plasma exchange was performed by centrifugation and filtration technique (95% and 4%, respectively), and immunoadsorption in 1% of the patients. Only fresh frozen plasma was used as replacement fluid in 69% of procedures. Adverse events were more frequent than in the general apheresis population (10% versus 5%, RR 1.9, CI 1.6–2.3). No death occurred due to apheresis treatment. Three percent of the procedures were interrupted. Bronchospasm and/or anaphylactic shock were present in two patients and one patient suffered from TRALI. At admission 26% were bedridden and needed to be fed. The risk of dying during the treatment period was significantly higher if the patient also suffered from a compromising disease, such as cancer. There was an inverse correlation between the ADAMTS13 level and the antibody titer (r = −0.47, p = 0.034).

Conclusions

Patients with TMA have an increased risk for moderate and severe AE compared to the general apheresis population. Many patients were severely ill at admission. The prognosis is worse if the patient also has a severe chronic disease. Even slightly increased ADAMTS13-antibody titers seem to have a negative impact on the ADAMTS13 levels.     

World apheresis registry report.

The establishment of national apheresis registries has been helpful to learn about therapeutic profiles and adverse event incidences. During 2003, the World Apheresis Registry was established and centers from all countries were invited to participate to register their apheresis activities (at www.iml.umu.se/medicin). MATERIAL: In this paper, we will report and analyze the first data retrieved from three centers, in 2 European countries, that registered a total of 388 therapeutic apheresis treatments in 122 patients, 95% due to acute indications. Statistical analyses were performed using an independent Student t-test and Fisher's test. A p-value of less than 0.05 was considered significant. RESULTS: Fifty percent of the treated patients were women. The mean age of the patients was 51 years (+/-17, range 16-84) and there was no difference between genders (w 50.4, m 51.6 years). Diagnoses for treatment were mainly neurological and vasculitis. In 63% peripheral access was used with a central double lumen catheter, 22% in the jugular vein, 8% in the subclavian vein and 6% the femoral vein. Significant inter-center differences were seen in regard to the access used. The main technique used was centrifugation for conventional plasma exchange (86%), while other modes were leukapheresis, erythrapheresis, platelet apheresis, LDL-apheresis and adsorption of antibodies. Citrate was the only anticoagulant in 92%. During plasma exchange procedures using centrifugation, replacement was by albumin only (58%) or plasma, the latter often in combination with albumin (42%). Adverse events (AEs) were noted in 11% of the procedures. Patients with hypocalcaemia side effects with tingling sensations were included in those data as mild AE and as moderate AEs if they received calcium (Ca) medication. No patient died due to adverse effects. A mild AE was present in 1.8% and moderate in 8.5%. During two procedures (0.5%), the AE was considered severe and therefore the procedure was interrupted. If those with AEs due to lower calcium were removed from analyses, 6.4% had AEs. Significantly more AEs were found when plasma was used as a replacement fluid (p=0.017, RR 2.05, CI 1.17-3.60). There were no differences in the incidence of AEs between genders. The number of procedures was too small to allow sub analyses of AEs in relation to the diagnoses. Adverse events were not related to the procedure used (p=0.095). Those who received additional Ca infusion during the procedure had no AEs (40 sessions) while the others who received no prophylactic Ca had an AE on 45 occasions (p=0.0141, RR 1.116, CI 1.08-1.15). CONCLUSION: Data from the registry shows that centers have various approaches to apheresis. One can learn from each other's experience to reduce side effects and improve efficacy. From these data we noted that prophylactic Ca infusion reduced side effects.     

Intravenous glutamine decreases lung and distal organ injury in an experimental model of abdominal sepsis

Introduction

The protective effect of glutamine, as a pharmacological agent against lung injury, has been reported in experimental sepsis; however, its efficacy at improving oxygenation and lung mechanics, attenuating diaphragm and distal organ injury has to be better elucidated. In the present study, we tested the hypothesis that a single early intravenous dose of glutamine was associated not only with the improvement of lung morpho-function, but also the reduction of the inflammatory process and epithelial cell apoptosis in kidney, liver, and intestine villi.

Methods

Seventy-two Wistar rats were randomly assigned into four groups. Sepsis was induced by cecal ligation and puncture surgery (CLP), while a sham operated group was used as control (C). One hour after surgery, C and CLP groups were further randomized into subgroups receiving intravenous saline (1 ml, SAL) or glutamine (0.75 g/kg, Gln). At 48 hours, animals were anesthetized, and the following parameters were measured: arterial oxygenation, pulmonary mechanics, and diaphragm, lung, kidney, liver, and small intestine villi histology. At 18 and 48 hours, Cytokine-Induced Neutrophil Chemoattractant (CINC)-1, interleukin (IL)-6 and 10 were quantified in bronchoalveolar and peritoneal lavage fluids (BALF and PLF, respectively).

Results

CLP induced: a) deterioration of lung mechanics and gas exchange; b) ultrastructural changes of lung parenchyma and diaphragm; and c) lung and distal organ epithelial cell apoptosis. Glutamine improved survival rate, oxygenation and lung mechanics, minimized pulmonary and diaphragmatic changes, attenuating lung and distal organ epithelial cell apoptosis. Glutamine increased IL-10 in peritoneal lavage fluid at 18 hours and bronchoalveolar lavage fluid at 48 hours, but decreased CINC-1 and IL-6 in BALF and PLF only at 18 hours.

Conclusions

In an experimental model of abdominal sepsis, a single intravenous dose of glutamine administered after sepsis induction may modulate the inflammatory process reducing not only the risk of lung injury, but also distal organ impairment. These results suggest that intravenous glutamine may be a potentially beneficial therapy for abdominal sepsis.     

A high blood level in the air trap reduces microemboli during hemodialysis

Previous studies have demonstrated the presence of air microemboli in the dialysis circuit and in the venous circulation of the patients during hemodialysis. In vitro studies indicate that a high blood level in the venous air trap reduces the extent of microbubble formation. The purpose of this study was to examine whether air microbubbles can be detected in the patient's access and if so, whether the degree of microbubble formation can be altered by changing the blood level in the venous air trap. This was a randomized, double‐blinded, interventional study of 20 chronic hemodialysis patients. The patients were assigned to hemodialysis with either an elevated or a low blood level in the air trap. The investigator and the patient were blinded to the settings. The numbers of microbubbles were measured at the site of the arteriovenous (AV) access for 2 min with the aid of an ultrasonic Doppler device. The blood level in the air trap was then altered to the opposite setting and a new measurement was carried out after an equilibration period of 30 min. Median (range) for the number of microbubbles measured with the high air trap level and the low air trap level in AV access was 2.5 (0–80) compared with 17.5 (0–77), respectively (P = 0.044). The degree of microbubble formation in hemodialysis patients with AV access was reduced significantly if the blood level in the air trap was kept high. The exposure of potentially harmful air microbubbles was thereby significantly reduced. This measure can be performed with no additional healthcare cost.