Inhibition of endotoxin-induced activation of the coagulation and fibrinolytic pathways using a recombinant endotoxin-binding protein (rBPI23)

A recombinant endotoxin-neutralizing protein, rBPI23, was shown to partially prevent endotoxin-induced activation of the fibrinolytic and coagulation systems in experimental endotoxemia in humans. In a placebo- controlled, blinded crossover study, eight volunteers were challenged twice with an intravenous bolus injection of endotoxin (40 EU/kg of body weight) and concurrently received either rBPI23 (1 mg/kg) or placebo (human serum albumin, 0.2 mg/kg). rBPI23 treatment significantly lowered the endotoxin-induced fibrinolytic response, ie, reduced the release of tissue-type plasminogen activator, urokinase- type plasminogen activator, plasminogen activator inhibitor antigen, and complex formation of plasmin alpha 2-antiplasmin (P = .0078 for each). Plasminogen activator inhibitor activity was also reduced, but not significantly according to the Hochberg method (P = .0304). The endotoxin-induced activation of the procoagulant state as reflected by increase in F1 + 2 fragments and TAT complexes was blunted by rBPI23 infusion (P = .0391 [not significant according to the Hochberg method] and .0078, respectively). These results indicate that rBPI23 is capable of reducing both the activation of the fibrinolytic and the coagulation systems after low-dose endotoxin infusion in humans.     

Chemoattractant-induced changes in surface expression and redistribution of a functional ligand for P-selectin on neutrophils

Adhesion between platelets and neutrophils is mediated through the interaction of P-selectin on activated platelets with a carbohydrate- containing structure on neutrophils, and occurs under both static and shear conditions. Recent studies using flow chambers have shown that neutrophils become activated after binding to surface-adherent platelets expressing P-selectin. The objective of the present study was to investigate the effect of such activation on the interactions of platelet P-selectin with its ligand on neutrophils. Flow cytometric analyses using P-selectin chimeras revealed that activation induced a rapid and marked reduction in chimera binding, with levels of binding decreased by 71% after 15 minutes of stimulation with the chemotactic agent, FMLP. Using a visual assay of platelet-neutrophil rosetting, we showed that the P-selectin ligand was translocated and clustered at the uropod of neutrophils following the shape changes and polarization induced by chemotactic stimulation. Activated neutrophils bound to surface-adherent platelets also displayed the clustering of P-selectin ligand at the uropod, and these neutrophils detached from the platelets when a shear stress (2 dynes/cm2) was applied through the adhesion chamber. These results indicate that chemotactic stimulation of neutrophils induces changes in the surface expression and distribution of a biologically relevant ligand for P-selectin, and that these changes might influence the adhesive interactions occurring between neutrophils and activated platelets.     

血浆置换显示干细胞移植后环孢素A引起的微血管病溶血性贫血和利福平的相应颜色反应

患者为1例39岁女性,患T/NK细胞淋巴瘤,在外周血异基因干细胞移植后15天,发生环孢素A(CSA)毒性相关的微血管病溶血性贫血(MAHA).因血清肌酐从移植前的0.4mg/dL,上升至移植后第9和15天的1.0和2.9 mg/dL.故停用CSA.     

High frequency oscillation in newborn infants with respiratory failure

Objective: To report ventilation strategies, survival and complications in 39 outborn infants treated with high frequency oscillatory ventilation (HFOV).
Methodology Data were collected prospectively between 1 May 1992 and 31 December 1993 on all infants treated with HFOV who had severe respiratory failure despite optimal conventional ventilation.
Results Twenty-eight out of 39 (72%) survived. Of the 15 infants with birthweights <1500g, eight survived. Best survival rates were for infants with pulmonary interstitial emphysema with air leak (4/5) and for infants of birthweight >1500g with hyaline membrane disease (8/8), and meconium aspiration syndrome (7/7). Three infants deteriorated while on HFOV and required extracorporeal membrane oxygenation. Complications were: (i) development of pulmonary interstitial emphysema (1); (ii) recurrence of pneumothorax (3); (iii) hypotension (2); and (iv) bronchopulmonary dysplasia (9). One of the eight infants weighing <1500g who received HFOV in the first week of life developed periventricular haemorrhage.
Conclusion The initial results of HFOV for severe respiratory failure were encouraging although a learning curve was encountered with its introduction.     

Internal sclerostomy with the Er:YAG laser using a gradient-index (GRIN) endoscope

BACKGROUND AND OBJECTIVE: To show that sclerostomy, a glaucoma filtering surgery, can be performed using an Er:YAG laser. Scarring at the filtering site, a recurrent problem, may be reduced through proper positioning of the sclerostomy by using an intraocular endoscope. MATERIALS AND METHODS: Ab interno full-thickness sclerostomies were performed on eye bank eyes with an Er:YAG laser through a custom made optical delivery system. The intraocular laser probe consisted of a low OH silica fiber inserted in a metallic tapered sheathing. A rigid intraocular endoscope based on gradient-index lenses allowed visualization of the filtration site. RESULTS: A clear view of the anterior chamber angle was obtained through the endoscope, allowing for precise location of the sclerostomy. Full-thickness sclerostomies could then be performed at the desired location. Histologic sections showed thermal necrosis less than 50 microm thick in tissue adjacent to the sclerostomy. CONCLUSIONS: A sclerostomy performed with a combined procedure using an Er:YAG laser and intraocular endoscopy increases the speed of the procedure. The use of a high-resolution intraocular endoscope may increase the success rate of ab interno laser glaucoma surgeries.     

Ki67, E-cadherin, and p53 as prognostic indicators of long-term outcome after liver transplantation for metastatic neuroendocrine tumors

BACKGROUND: Patients suffering from hepatic metastases of neuroendocrine tumors (NET) are potential candidates for orthotopic liver transplantation. Because recurrence rates are high and outcome is variable, prognostic indicators are required. The aim of our study was to identify predictors of long-term survival with a focus on the impact of tumor biology. METHODS: We retrospectively analyzed 19 patients who received an orthotopic liver graft for metastatic NET at the Medizinische Hochschule Hannover. Expression of Ki67, E-cadherin, and p53 was studied immunohistochemically in metastases of neuroendocrine tumors of the explanted livers. RESULTS: Patients were followed up to 146 months after liver transplantation. Six patients died during follow-up. The resulting 1-, 5-, and 10-year survival rates are 89%, 80%, and 50%, respectively. All deaths during long-term follow-up were tumor-associated. Recurrence was diagnosed in 12 patients between 2 weeks and 48 months after liver transplantation. Three patients are without tumor recurrence more than 8 years after liver transplantation. Survival in the 5 patients with low Ki67 and regular E-cadherin staining was significantly better than in the 12 patients with high Ki67 or aberrant E-cadherin expression (7-year survival 100% vs. 0%, respectively, log rank P=0.007). p53 expression did not significantly improve prognostic accuracy. CONCLUSIONS: We conclude that analysis of Ki67 and E-cadherin expression may improve the identification of patients with a favorable prognosis after liver transplantation for metastatic neuroendocrine tumors.     

Indicators for longterm survival after the transjugular portosystemic intrahepatic shunt procedure

Introduction. Complications of portal hypertension can be treated effectively by the transjugular intrahepatic portosystemic shunt procedure (TIPS). Indicators for long time survival after TIPS implantation are presented. Patients and Methods. From September 1992 until May 1995 forty-two consecutive patients (26 male, 16 female) with liver cirrhosis complicated by variceal bleeding (n = 27) or refractory ascites (n = 15) were treated by TIPS implantation and followed up clinically in a prospective, open study. The follow up period range was 5–3278 days. Univariate and multivariate regression analyses were applied to determine the correlation between patient characteristics and long term survival after TIPS implantation. The indicators were dichotomized at the median. The outcome variable was dichotomized. Positive outcome was defined as survival longer than three years without liver transplantation, all other outcomes were regarded as negative. Survival rates were determined for all patients and for subgroups according to results of the regression analyses. Results. During follow-up liver transplantation was performed in 8 of the 42 patients. 29 patients died. Mean survival was 1440 (±1060) days. Survival after one, two, three and six years was 76% (n = 32), 69%(n = 29), 62% (n = 26) and 38% (n = 16), respectively. The multivariate regression analysis revealed a significant better survival related to a prothrombine time >70%, MEGX synthesis >30 μg/l, and ICG clearance <13 min. Patients with high ICG clearance (OR = 1.9), high MEGX synthesis (OR = 5.0) or high prothrombine time scores (OR = 5.2) had a significantly longer survival. This survival advantage increased with follow up time. Conclusion. Longterm survival after TIPS implantation is influenced by the initial liver function. This survival advantage increases during follow up and is most pronounced after 6 years.