Acquired C1 esterase inhibitor deficiency

A case of acquired C1 esterase inhibitor deficiency and its anaesthetic implications is presented. Prophylaxis against angioneurotic oedema using danazol and tranexamic acid is described and the resultant complication of mesenteric venous thrombosis reported.     

Use of Neoral C2 monitoring: a European consensus

Large-scale clinical trials using C(2) monitoring of cyclosporine (CsA) microemulsion (Neoral) in renal transplant recipients have demonstrated low acute rejection rates and good tolerability with a low adverse event profile in a variety of settings: with or without routine induction therapy; in combination with mycophenolate mofetil; with standard-exposure or low-exposure Neoral; and in patients with immediate or delayed graft function. In liver transplantation, C(2) monitoring significantly reduces the severity and incidence of acute rejection compared with C(0) monitoring, without adverse consequences in terms of renal function or tolerability. Different C(2) targets are appropriate depending on adjunctive immune suppression, level of immunologic risk, CsA tolerability, risk of renal toxicity and time since transplantation. CsA absorption may increase substantially in most patients during the first 1-2 weeks post-transplant, and this should be taken into account to avoid overshooting C(2) target range. A patient with a low C(2) value may be either a low or a delayed absorber of CsA, or be a normal absorber who is receiving too low a dose of Neoral. C(2) monitoring alone is insufficient to differentiate between these types of patients, and measurement of additional timepoints is recommended. Adopting C(2) monitoring in maintenance transplant patients identifies those who are overexposed to CsA. In summary, randomized, prospective, multicenter studies and single-center trials have evaluated Neoral C(2) monitoring within a range of regimens in different organ types, providing a robust evidence base for the benefits of this sensitive monitoring technique.     

Fractionated Plasma Separation and Adsorption System: A Novel System for Blood Purification to Remove Albumin Bound Substances

The removal of albumin bound substances has gained increasing interest in different diseases, especially in acute and chronic liver disease. Therefore, a new system, the fractionated plasma separation and adsorption (FPSA) system, was developed based on combined membrane and adsorbent blood purification techniques. The most important contribution to the FPSA system was the development of a new polysulfone hollow-fiber filter, which is characterized by a sieving coefficient of 0.89 for human serum albumin (HSA) but only of 0.17 for fibrinogen, and 0 (zero) for IgM immunoglobulins. Using a closed filtrate circuit connected to the new polysulfone filter which integrates 1 or 2 adsorption columns and also a high flux dialyzer adapted to a dialysis machine, the FPSA system opens excellent possibilities for the relatively specific removal of albumin bound substances from the blood such as albumin bound bilirubin or even tryptophan. In comparison to other systems (for example, the Molecular Adsorbent Recirculating System [MARS] and albumin dialysis systems), the FPSA system enables much higher elimination of strongly bound albumin substances. The first clinical investigations have recently started based on a modified dialysis machine designed with all necessary safety measures.     

Temperature and Albumin Effects on Adsorption of Bilirubin from Standard Solution using Anion-Exchange Resin

The efficacy of plasma bilirubin sorption for the treatment of patients with hepatic dysfunction can be determined by a quantitative evaluation of bilirubin adsorption. The objective of this study is to examine the effects of temperature (4-42 degrees C) and albumin concentration (0.5-5.0 g%) on bilirubin removal from solution by an anion-exchange resin. For a constant albumin concentration, adsorption increased with temperature. The adsorption isotherm curves did not show saturation at the lower temperatures. At a constant temperature, adsorption increased with decreasing albumin concentration. A one-parameter model was used to describe the data for bilirubin adsorption at all temperatures and for all initial concentrations of bilirubin and albumin. This parameter increased monotonically with temperature and decreased monotonically with albumin concentration. From a practical clinical point of view, bilirubin sorption may be increased by operation of the sorbent column at above ambient temperature.     

Influence of Blood Flow on Adsorption of β2-Microglobulin onto AN69 Membrane

Abstract: Adsorption onto the dialyzer membrane is a contributing factor to the elimination of β₂-microglobulin (β₂M) from the sera of uremic patients. The purpose of this prospective study was to ascertain the influence of the blood flow rate on adsorption of β₂M onto the polyacrylonitrile (AN69) hollow-fiber dialyzer membrane in 8 pa tients during regular hemodialysis (HD). Blood first passed through a low-flux polysulfone dialyzer and then through an AN69 dialyzer, which was not in contact with the dialysis fluid. During the investigation period (first hour of the HD session), the blood flow rate was 100 ml/min (first part of the study), 200 mumin (second part of the study), and 300 ml/min (third part of the study). Ultrafiltration was not performed during the investigation period. At the start of the HD sessions, the serum concentration of β₂M in the afferent blood line did not differ significantly among the 3 parts of the study. Serum β₂M was measured in samples taken from the afferent and efferent blood lines of the AN69 dialyzer at 5,10, 15, 30, 45, and 60 min. The serum β₂M concentration decreased significantly in blood that had passed through the AN69 dialyzer. This decrease, indicating membrane adsorption, was maximal during the first part and minimal during the third part of study. The decrease in the contact time between the blood and the AN69 could be the underlying cause. The calculated quantities of β₂M adsorbed onto the AN69 membrane (44.2 ± 10.2, 43.2 ± 12.1, and 42.6 ± 17.3 mg) did not differ significantly among the 3 parts of the study. These results suggest that an increase in blood flow rate from 100 to 300 ml/min did not significantly affect the quantity of β₂M adsorbed onto the AN69 membrane.     

Recurrence-Free Long-Term Survival After Liver Transplantation in Patients with 18F-FDG Non-Avid Hilar Cholangiocarcinoma on PET

The aim of this retrospective study was to assess the value of ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG-PET) for predicting biological tumor behavior and outcome after liver transplantation (LT) in patients with otherwise unresectable hilar cholangiocarcinoma (HC). Preoperative ¹⁸F-FDG-PET scanning was performed in 13 patients with type IV Klatskin tumor before LT. PET+ status indicated patients with an increased pretransplant ¹⁸F-FDG uptake, whereas PET− recipients had no increased preoperative ¹⁸F-FDG uptake on PET. Pretransplant PET findings were correlated with histopathological tumor characteristics and patient outcome after LT. Eight patients demonstrated positive preoperative PET findings (61.5%), whereas five patients had no increased preoperative ¹⁸F-FDG tumor uptake (38.5%) on PET. One PET+ patient died after 1 month due to liver allograft dysfunction. Seven PET+ liver recipients developed tumor recurrence, whereas five PET− patients were tumor-free alive after a median of 76 months post-LT (p = 0.001). The 2-year recurrence-free survival rate after LT was 100% in PET− patients and 28.6% in the PET+ population (log-rank = 0.008). Our results suggest that patients with ¹⁸F-FDG non-avid HC on PET may achieve recurrence-free long-term survival after LT.     

Antispermatogenic/antiandrogenic properties of solasodine (C27H43O2N) obtained from solanum xanthocarpum berries on the male genital tract of dog (Canis-familiaris). A Histophysiological approach

Chronic administration of solasodine (20 mg/kg alt. day for 30 days) caused testicular lesions resulting in a severe impairment of spermatogenic elements. The epididymides were devoid of spermatozoa. Total protein, sialic acid and glycogen contents of the testis and epididymis were reduced significantly whereas the testicular cholesterol was elevated. Acid Phosphatase enzyme activity of the testes was low after solasodine treatment. Serum enzymes (SGPT, alkaline phosphatase) serum protein, triglycerides, non esterified fatty acid levels were in normal range when compared with their own controls. Cholesterol and phospholipid levels were elevated after solasodine treatment to intact dogs. Reduced androgen production was reflected in low levels of sialic acid in the testes and epididymides and reduced Leydig cell nuclei. Castration alone brought about reduction in size of the epididymis. Castration followed by solasodine treatment caused epididymal degeneration. Simultaneous administration of TP to solasodine treated castrated dogs failed to stimulate the epididymal growth. Antispermatogenic/antiandrogenic activity of the compound solasodine is discussed. Solasodine administration in dogs definitely rendered the male infertile as evidenced by the absence of sperms in the cauda epididymis and ductus deferens.     

A Combined tc-Po2 and Skin Blood Flow Sensor

A new approach to the determination of energy delivered to the skin during transcutaneous oxygen tension (tc-PO2) measurements was tested. The test was carried out using a tc-PO2 electrode constructed with an active thermal shield in order to provide more sensitive and specific heat transport measurements, and consequently to create the possibility of determining skin blood flow rates. The oxygen measurement properties did not differ from the conventional tc-PO2 electrode. In vivo measurements were performed on 11 adult volunteers. Skin blood flow was determined by a blood flow cessation technique to be 0.124 +/- 0.053 ml . cm-2 . min-1 at the start of the experiments, rising to 0.164 +/- 0.61 ml . cm-2 . min-1. Tc-PO2 changed from 56.2 +/- 9.8 mmHg (7.5 +/- 1.3 kPa) to 68.3 +/- 9.0 mmHg(9.1 +/- 1.2 kPa). It is concluded that a thermally shielded electrode makes it possible to determine the convectional component of the heat loss from the electrode to the skin and consequently to compute a relative measure of skin blood flow rate. The observed change in computed skin blood flow rate was correlated to the observed change in tc-PO2 (P less than 0.1).     

Determination of Skin Blood Flow by 133Xe Washout and by Heat Flux from a Heated tc-Po2 Electrode

¹³³Xe washout measurements were used to determine cutaneous and subcutaneous blood flow beneath a specially designed double-thermostated tc-Po₂ electrode. The skin blood flow was determined using thermal methods based on reduced heat dissipation during blood flow cessation. A total of 20 measurements were performed on two healthy volunteers, using the volar side of the right forearm as the experimental area. Cutaneous as well as subcutaneous blood flow increased with increasing electrode temperature. The cutaneous blood flow increased from 12.3 ± 1.3 ml (100 g)^-1-min^-1 (37C) to 49.1 ± 5.4 ml (100 g)^-1.min^-1 (45C) and the subcutaneous values from 20.9 ± 0.2 ml (100 g)^-1 -min^-1 to 57.3 ± 0.5 ml (100 g)^-1 -min^-1. Preheating of the measuring area or injection of papaverine as blood flow accelerator did not increase the maximum blood flow values. A considerable inter-individual difference between cutaneous and subcutaneous blood flow was observed, but in spite of that a good overall correlation between the ¹³³Xe washout measurements and the two thermal flow measurements was found (r = 0.932 and 0.945, respectively). It is concluded that in some cases, but not always, measurements of tc-Po₂ at electrode temperatures of 45C take place on a maximally perfused skin and that it is possible to determine skin blood flow by means of determinations of the heat dissipated from the tc-Po2 electrode to the underlying skin.     

肺部病变类型及大小对18F-FDG显像T/NT比值的影响

目的探讨肺部不同病变病理类型及病灶大小对18 F-FDG摄取差异的影响。方法分析155例患者胸部病变的18F-FDG显像,根据手术、活检等病理结果测量病灶T/NT比值及病灶大小,并分析其相关性。结果恶性病变（肺鳞癌、肺腺癌和小细胞肺癌）及结核摄取18 F-FDG均高于炎性改变,恶性病变T/NT比值与病灶大小呈正相关（P均〈0.05）;但结核及炎性改变T/NT比值与病灶大小无相关性（P均〉0.05）。结论恶性肿瘤18 F-FDG显像T/NT比值明显大于炎性病变,但结核仍是导致假阳性的重要因素。恶性病变大小与T/NT比值呈正相关,良性病变大小与T/NT比值无明显相关。     

基于深度学习重建列表模式提取儿童18F-FDG PET/CT低剂量图像

目的 探讨基于深度学习(DL)重建列表模式提取低剂量图像用于儿童¹⁸F-FDG PET/CT检查的可行性。方法 对93例患儿行全身¹⁸F-FDG PET/CT,分别以120秒/床位行标准全剂量扫描、20秒/床位行快速扫描,之后以列表模式于120秒/床位图像中提取20秒/床位图像。将20秒/床位图像与以列表模式提取的20秒/床位图像传输至DL平台进行重建,分别获得相应全剂量图像(DL-f20s、DL-20s);对比标准全剂量120s、DL-f20s、DL-20s图像的靶本比(TBR)、对比噪声比(CNR)、变异系数(CV)、图像质量主观评分,以及肝血池、纵隔血池、肌肉血池及原发病灶最大标准摄取值(SUV_max)和平均标准摄取值(SUV_mean),分析基于DL-f20s与DL-20s图像所获SUV_max及SUV_mean的一致性。结果 120s、DL-f20s和DL-20s图像的主观质量Likert评分、TBR、CNR、CV及各血池、病灶的SUV_max...     

18F-FDG PET/CT在骨与软组织肉瘤中的应用进展

骨与软组织肉瘤发病率相对较低,但多数恶性程度高,预后差,早期诊断是改善预后的关键。~(18)F-FDG PET/CT可用于骨与软组织肉瘤的诊断及鉴别诊断、肿瘤分级、确定活检部位、检测复发及转移、评价疗效及预后等各方面。本文就~(18)F-FDG PET/CT在骨与软组织肉瘤中的应用进展进行综述。     

Sweep Gas Flowrate and C02 Exchange in Artificial Lungs

Abstract A simple analysis and graphic result are presented for characterizing the dependence of CO₂ exchange on the sweep gas (ventilating gas) flowrate in artificial lungs. The analysis requires no knowledge of the device-specific mass transfer characteristics of an artificial lung, nor does it require detailed mathematical modeling or computer simulation. Rather, it uses appropriate normalization to establish generic features of the gas flow dependency of CO₂ exchange that are applicable to all artificial lung devices. Principal results are that the transition from relatively gas flow-sensitive to gas flow-insensitive CO₂, exchange occurs at sweep gas flowrates of approximately 40–60 times the CO₂ exchange rate. Achieving a CO₂ exchange rate within 85% of maximal (for a given oxygenator and blood-side conditions) requires a sweep gas flowrate of no less than approximately 50 times the nominal CO₂ exchange rate. When the sweep gas flowrate is less than 20 times the CO₂ exchange rate, CO₂ exchange is highly gas flow dependent and less than one-half the maximal possible rate.     

肺腺癌患者18F-FDG PET/CT半定量参数与EGFR基因突变亚型的关系

目的探讨肺腺癌患者~(18)F-FDG PET/CT半定量参数与表皮生长因子受体(EGFR)基因突变亚型间(19号外显子缺失突变和21号外显子点突变)的关系。方法收集64例肺腺癌患者术前~(18)F-FDG PET/CT及EGFR基因突变资料。葡萄糖代谢显像原发灶半定量参数包括最大标准化摄取值(SUV_(max))、平均标准化摄取值(SUV_(mean))、肿瘤代谢体积(MTV)和总糖酵解量(TLG)。经单因素和多因素Logistic回归分析评估各参数与突变亚型间的关系,通过AUC评估关联效能。结果 19号、21号外显子突变比例为23∶41。单因素分析显示,作为连续变量,原发灶最大径较小[OR=0.942,95%CI(0.890,0.998)]及低水平原发灶MTV(pMTV)[OR=0.957,95%CI(0.923,0.991)]更可能是21号外显子点突变;作为分类变量,原发灶最大径较小[26.5 mm:OR=3.759,95%CI(1.284,11.005)]、高水平SUV_(mean)[≥4.35:OR=4.267,95%CI(1.088,16.726)]及低水平pMTV[11.2 cm~3,OR=7.000,95%CI(1.798,27.253)]更易发生21号外显子点突变。多因素分析仅发现分类变量低水平pMTV更易发生21号外显子点突变(OR=8.093,P=0.041)。结论 EGFR基因突变肺腺癌患者原发灶~(18)F-FDG PET/CT半定量参数可能与19和21号外显子突变亚型存在一定相关性,但关联程度有限。     

18F-FDG PET/CT评价初诊T细胞淋巴瘤代谢活性与免疫表型的相关性

目的观察初诊T细胞淋巴瘤~(18)F-FDG代谢活性与淋巴瘤免疫表型的关系。方法回顾性分析64例初诊T细胞淋巴瘤患者,均于治疗前接受~(18)F-FDG PET/CT检查且经病理学确诊。测量活检部位PET/CT最大标准摄取值(SUV_(max)),分析其与免疫表型之间的相关性。结果 64例活检部位SUV_(max)为2.23～24.42,中位SUV_(max)为8.02,与Ki-67、CD5表达呈正相关(r_s=0.31、P=0.02,r_s=0.81、P0.01),而与其他免疫学指标均无相关性(P均0.05)。结论 T细胞淋巴瘤代谢活性与Ki-67和CD5表达呈正相关;~(18)F-FDG PET/CT可作为无创评估Ki-67和CD5免疫表达的影像学手段。     

18F-FDG-Uptake of Hepatocellular Carcinoma on PET Predicts Microvascular Tumor Invasion in Liver Transplant Patients

Vascular invasion of hepatocellular carcinoma (HCC) is a major risk factor for poor outcome after liver transplantation (LT). The aim of this retrospective analysis was to assess the value of preoperative positron emission tomography (PET) using ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) in liver transplant candidates with HCC for predicting microvascular tumor invasion (MVI) and posttransplant tumor recurrence.
Forty-two patients underwent LT for HCC after PET evaluation. Sixteen patients had an increased ¹⁸F-FDG tumor uptake on preoperative PET scans (PET +), while 26 recipients revealed negative PET findings (PET−) pre-LT. PET− recipients demonstrated a significantly better 3-year recurrence-free survival (93%) than PET + patients (35%, p < 0.001). HCC recurrence rate was 50% in the PET + group, and 3.8% in the PET—population (p < 0.001). PET + status was identified as independent predictor of MVI [hazard ratio: 13.4]. Patients with advanced PET negative tumors and patients with HCC meeting the Milan criteria had a comparable 3-year-recurrence-free survival (80% vs. 94%, p = 0.6).
Increased ¹⁸F-FDG uptake on PET is predictive for MVI and tumor recurrence after LT for HCC. Its application may identify eligible liver transplant candidates with tumors beyond the Milan criteria.     

18F-FDG PET/CT评价非霍奇金淋巴瘤骨髓浸润

目的探讨^18F-FDG PET／CT评价非霍奇金淋巴瘤（NHL）骨髓浸润的临床应用价值,并与骨髓活检（BMB）及流式细胞分析（FCM）进行比较。方法回顾性分析89例经病理证实且未经治疗的NHL患者^18F-FDG PET／CT资料,其中侵袭性NHL76例,惰性NHL13例。所有患者均在^18F-FDG PET／CT检查2周内接受BMB及FCM,对^18F-FDG PET／CT显示骨髓局灶性^18F—FDG摄取增高而BMB及FCM阴性患者,根据PET／CT所示骨髓异常部位再次行BMB确定骨髓是否受累。结果89例NHL患者中,根据BMB、FCM及PET／CT引导下再次BMB结果,共检出骨髓浸润26例,检出率为29．21％（26／89）,PET／CT检出率为21．35％（19／89）。PET／CT诊断骨髓浸润的灵敏度为73．08％（19／26）,特异度为96．83％（61／63）,准确率为89．89％（80／89）,阳性预测值为90．48％（19／21）,阴性预测值为89．71％（61／68）。BMB及FCM检出率均为19．10％（17／89）,PET／CT较BMB、FCM骨髓浸润检出率稍高,但差异无统计学意义（P〉0．05）。将PET／CT、FCM及BMB三种方法联合诊断骨髓浸润,其检出率高于其中任意一种方法（P〈0．05）。PET／CT对侵袭性NHL骨髓浸润的检出率22．37％（17／76）高于对惰性NHL骨髓浸润的检出率15．38％（2／13,P〈0．06）。结论^18F-FDG PET／CT在诊断NHL骨髓浸润中有较高的应用价值。对局灶性骨髓浸润患者,PET／CT有助于引导BMB部位,提高骨髓浸润的检出率。PET／CT未检出骨髓浸润的惰性NHL患者,应进一步行BMB及FCM检查。推荐PET／CT、FCM及BMB三种方法联合应用判断NHL骨髓浸润,从而更准确地进行分期、治疗及判断预后。     

Influence of direct and indirect allorecognition pathways on CD4+CD25+ regulatory T-cell function in transplantation

While both direct and indirect allorecognition are involved in allograft rejection, evidence to date suggests that tolerance is primarily dependent on indirect pathway-triggered CD4+CD25+ T cell-mediated immunoregulation. However, the precise influence of these two pathways on CD4+CD25+ T-cell function has not been addressed. In the current study, we have utilized an adoptive transfer model to assess selectively how the absence of either direct or indirect allorecognition affects CD4+CD25+ T-cell function. The effects of the loss of the direct pathway were assessed by transplanting skin grafts from minor histocompatibility mismatched B10.D2 (H-2d) donors onto Balb/c (H-2d) recipients, or by placing bone marrow chimeric DBA/2 (H-2d/H-2b) allografts onto C57BL/6 (H-2b) hosts. The requirement for indirect allorecognition was tested by grafting DBA/2 skin allografts onto either C57BL/6- or MHC-II-deficient C57BL/6 recipients. We report here that although CD4+CD25+ regulatory T cells can suppress both directly and indirectly generated alloresponses, immunoregulation is favored when indirect presentation is the sole mechanism of allorecognition. Hence, in the absence of indirect presentation, net CD4+CD25+ T cell-dependent immunoregulation is weak, and high ratios of CD4+CD25+ to CD4+CD25 T cells are required to ensure graft survival.     

The effect of 24,25 dihydroxyvitamin D3 on calcium efflux: the role of protein kinase C

SUMMARY: 24,25 dihydroxyvitamin D₃ (24,25(OH)₂D₃) is more abundant than 1,25(OH)₂D₃ in the serum. 1,25 dihydroxyvitamin D₃, a potent calciotropic metabolite of vitamin D, has been shown to induce calcium efflux from bone. This action is probably mediated, in part, by protein kinase C (PKC). to determine whether 24,25(OH)₂D₃ affects calcium flux in bone, neonatal rat calvaria were cultured and the effect of 24,25(OH)₂D₃ on calcium flux and signal transduction pathways were evaluated. Compared with a control, 24,25(OH)₂D₃ (10⁸ mol/L) inhibited basal net calcium efflux. 24,25 dihydroxyvitamin D₃ also inhibited net calcium efflux induced by the phorbol ester 12 Myristate 13-Acetate (PMA). Translocation of PKC from the membrane to the cytosolic fraction was rapidly and transiently induced by 24,25(OH)₂D₃. However, 24,25(OH)₂D₃ had no effect on cyclic AMP (cAMP) production. In conclusion, 24,25(OH)₂D₃ has a direct effect on bone by inhibiting net calcium efflux which is probably mediated by the deactivation of PKC.     

The Preparation of a Urokinase-AT-III-PGE1-Methyldopa Complex, and Its Effects on Platelet Adhesion, Coagulation Times, Protein Adsorption, and Fibrinolysis

Modifications of urokinase by substances possessing useful therapeutic activity permit combined action preparations to be obtained. Here an attempt was made to develop a complex having combined action for therapeutic activity. The possibility of repeatedly modified urokinase with antithrombin-III-methyldopa-prostaglandin E1 had been experimentally demonstrated. The complex was immobilized on albuminated substrate, which showed fibrinolytic, anticoagulant, and antiplatelet effects simultaneously, in addition to the normal antihypertensive action of methyldopa. The complex immobilized substrate also demonstrated an increase in albumin-surface attachment and a reduction in fibrinogen binding. This may be one of the parameters for a reduced platelet-surface attachment, which may also improve the blood compatibility of the substrate. The approaches suggested indicate the possible new ways of creating nonthrombogenic surfaces with wider applications. A better understanding of the mechanism of these complexes are needed in in vivo conditions to correlate these findings.