Transfusion-acquired cytomegalovirus infection in neonates. A prospective study

The incidence of cytomegalovirus (CMV) infection was determined in 114 transfused neonates of any birthweight born to CMV antibody-negative mothers. In a second phase of this study, an additional 28 transfused infants weighing less than 1250 g, born to both CMV antibody-negative and antibody-positive mothers, were followed. All infants underwent weekly virus culture and monthly serology during hospitalization and at 6 to 12 weeks after their last transfusion. Only one of 126 (0.8%) seronegative infants and one of 16 (6.3%) seropositive infants developed CMV infection. If the assumption is made that the CMV-infected infant received only 1 unit of infectious blood, the risk of transfusion-acquired CMV infection to seronegative infants is 0.16 percent per cellular unit transfused or 0.37 percent per seropositive cellular unit transfused. Despite similarities in the prevalence of CMV antibody in the donor population, the age of blood products used, and the mean number of donor exposures, a significantly lower incidence of CMV infection was found in the seronegative transfused infants than that in two previously published studies (p less than 0.01, p less than 0.001). Because no mortality and very little morbidity could be attributed to transfusion-acquired CMV infection in the nurseries, the authors can see no justification for the provision of specialized blood components for the prevention of CMV infection in this patient population.     

Selective Aortic Arch Perfusion Using Serial Infusions of Perflubron Emulsion

Objective : To determine whether selective aortic arch perfusion (SAAP) using serial infusions of oxygenated perflubron emulsion combined with aortic epinephrine (AoE) administration is more effective than conventional therapy in treating cardiac arrest.
Methods : An experimental cardiac arrest model (10 min ventricular fibrillation and 2 min CPR) was used with 12 mixed-breed canines, randomized into 2 groups: control ( n = 6), CPR and IV epinephrine, 0.01 mgkg, at 12 rnin and then every 3 min; or AoE-SAAP ( n = 6), CPR and aortic epinephrine, 0.01 mgkg, at 12 rnin and then every 3 min, and serial SAAP with oxygenated 60% weightholume (w/v) perflubron emulsion as follows: 300 mL over 30 sec at 12 rnin as continuous SAAP without CPR; 150 mL over 20–30 sec at 15 min and 18 rnin as pulsed diastolic SAAP during CPR.
Results : AoE-SAAP resulted in increased coronary perfusion pressure (CPP) and return of spontaneous circulation (ROSC) compared with control. CPR-diastolic (release phase) CPP during pulsed diastolic SAAP was similar to or greater in magnitude than the CPP generated during the initial SAAP infusion without CPR. ROSC for control was 0/6 and for AoE-SAAP was 416 (p < 0.05, Fisher's exact test). Time from initiation of CPR to ROSC with a sustained systolic aortic pressure >60 mm Hg was 8.0 ± 1.2 rnin in the 4 resuscitated AoE-SAAP animals.
Conclusion : The combination of AoE with SAAP infusions of oxygenated perflubron emulsion was more effective than conventional resuscitation therapy. Pulsed diastolic SAAP is a promising method for performing SAAP.     

Rates of sustained virological response 12 weeks after the scheduled end of direct‐acting antiviral (DAA)‐based hepatitis C virus (HCV) therapy from the National German HCV registry: does HIV coinfection impair the response to DAA combination therapy?

Objectives

The European Association for the Study of the Liver (EASL) treatment recommendations for hepatitis C no longer discriminate between HIV/hepatitis C virus (HCV)‐coinfected and HCV‐monoinfected patients. However, recent data from Spain are questioning these recommendations on the basis of the findings of higher relapse rates and lower cure rates in HIV/HCV‐infected subjects. The aim of our study was to compare HCV cure rates in monoinfected and coinfected patients from Germany.

Methods

Data acquired from the Deutsches Hepatitis C‐Registry were analysed. A total of 5657 HCV‐monoinfected subjects and 488 HIV/HCV‐coinfected patients were included in the study. Rates of sustained virological response 12 weeks after the scheduled end of therapy (SVR12) were collected in both subgroups and in cirrhotic and noncirrhotic patients.

Results

HIV/HCV‐coinfected patients were more frequently male (84.6% vs. 56.4%, respectively; P < 0.001) and younger than HCV‐monoinfected subjects (46.5 ± 9 vs. 53.8 ± 12.5 years, respectively; P < 0.001). The CD4 blood cell count was > 350 cells/μL in 63.1% of HIV‐positive subjects and 88.7% were on antiretroviral therapy. SVR12 rates were 90.3% (5111 of 5657) in our HCV‐monoinfected cohort and 91.2% (445 of 488) in our coinfected patients. Liver cirrhosis was confirmed in 1667 of 5657 (29.5%) monoinfected patients and 84 of 488 (17.2%; P < 0.001) coinfected patients. SVR12 rates did not differ between HCV‐monoinfected and HIV/HCV‐coinfected patients with liver cirrhosis (87.8% vs. 89.3%, respectively; P = 0.864). A treatment duration of 8 weeks did not reduce the percentage of patients with SVR12 in either subgroup (93.7% in both groups).

Conclusions

We found high SVR12 rates in monoinfected as well as coinfected individuals. No differences were detected between the two subgroups regardless of whether there was accompanying liver cirrhosis or a shortened treatment duration.

     

Modulation of neutrophil oxidative responses to soluble stimuli by platelet-activating factor

The role of platelet activating factor (PAF) as a regulator of human neutrophil superoxide (O2-) generation in response to soluble and particulate stimuli was examined. At concentrations greater than 10(-7) mol/L, PAF alone induced a brief burst of O2- production. When cells were exposed to PAF and either the chemotactic peptide n-formyl- methionyl-leucyl-phenylalanine (FMLP 10(-7) mol/L) or the tumor promoter phorbol myristate acetate (PMA 10 ng/mL), a marked synergistic augmentation of O2- release was noted when compared to control cells stimulated with FMLP or PMA alone. Mean percentage of enhancement by 10(-5) mol/L of PAF was 297% +/- 35% (n = 9) of control responses to FMLP and 185% +/- 16% (n = 3) of control responses to PMA. Consistent enhancement occurred with PAF concentrations of as low as 10(-9) mol/L. Enhancement could be demonstrated when neutrophils were exposed to PAF either at the same time as, or up to 60 minutes prior to, the second stimulus, and was neither reversed by removal of PAF from the medium prior to addition of FMLP or PMA nor dependent on the presence of extracellular divalent cations. Continuous recordings revealed that the enhancement was due to an increased maximal rate of O2- production. In contrast, PAF concentrations up to 10(-5) mol/L had only a minimal effect on the response to neutrophils to opsonized zymosan. Analysis of the enhancing properties of lipids structurally related to PAF revealed that the critical moiety was the saturated fatty acid at position 1. These results indicate the presence of a PAF-mediated positive feedback loop whereby the oxidative burst induced by some soluble stimuli is augmented. Modulation of neutrophil O2- production by PAF may serve to amplify neutrophil oxidative responses at sites of inflammation.     

大鼠、兔和人关节软骨组织形态学的比较

目的:观察比较大鼠、兔和人正常关节软骨组织学结构和关节炎软骨病理变化的差异。方法:实验于2006-08/2007-04在北京大学运动医学研究所完成。取大鼠、兔和人正常的关节滑车软骨和关节炎的滑车软骨,人关节软骨来源告知患者并征得同意,进行苏木精-伊红和甲苯胺蓝组织学染色,观察正常关节软骨的形态结构及关节炎软骨的病理变化。结果:关节软骨具有明显的分层,3者的主要区别在于软骨的第三层和潮线。大鼠软骨的第三层是典型的肥大细胞,无潮线;兔软骨的第三层是典型的柱状细胞层,潮线明显;人的软骨第三层为深层带,细胞较大,形态不规则,有多核细胞存在,有明显的潮线。正常软骨甲苯胺蓝染色均匀。关节炎软骨变化从表面开始,大鼠表现为表层软骨纤维样变,肥大细胞消失;兔和人表现为表层软骨细胞坏死,深层细胞排列紊乱。甲苯胺蓝染色失染或染色不均。结论:大鼠、兔和人的关节软骨结构不尽相同,主要差别在第三层和潮线的有无。关节炎软骨的变化也各有异同,但兔的软骨变化更接近于人。     

Activation of the contact system in insect-sting anaphylaxis: association with the development of angioedema and shock

A postulated role of the contact system in anaphylactic reactions to insect stings was investigated. During prospective, in-hospital sting challenge, we collected serial blood samples from five normal volunteers and 16 patients with a history of insect-sting anaphylaxis. Activation of the contact system was assessed by measuring plasma levels of factor XIIa-C1-inhibitor and kallikrein-C1-inhibitor complexes as well as those of cleaved high molecular weight kininogen (HK). In addition, antigenic levels of (pre)kallikrein, factor XII, and HK were measured. No significant changes in contact system parameters were observed in any of the five volunteers or the four patients who did not develop an anaphylactic reaction after sting challenge. In contrast, significant changes in contact system parameters occurred in 7 of the 12 patients with anaphylactic symptoms after challenge. Peak levels of either C1-inhibitor complex were found 5 minutes after the onset of anaphylactic symptoms. The increase in C1-inhibitor was most pronounced in the 4 patients with angioedema, 2 of which also developed shock. However, activation of HK was observed in all four patients with angioedema, the two patients with shock but no angioedema, as well as in 1 of the remaining 6 patients with anaphylactic symptoms other than angioedema or shock. Thus, activation products of the contact system may be involved in the pathogenesis of angioedema and shock in insect- sting anaphylaxis.