Risk factors for liver abscess formation in patients with blunt hepatic injury after non-operative management.

PURPOSE: To identify risk factors for liver abscess formation in patients with blunt hepatic injury who underwent non-operative management (NOM). METHODS: From January 2004 to October 2008, retrospective data were collected from a single level I trauma center. Clinical data, hospital course, and outcome were all extracted from patient medical records for further analysis. RESULTS: A total of 358 patients were enrolled for analysis. There were 13 patients with liver abscess after blunt hepatic injury. Patients with abscess had a significant increase in glutamic oxaloacetic transaminase (GOT, p = 0.006) and glutamic pyruvic transaminase (GPT, p < 0.0001), and a decrease in arterial blood pH (p = 0.023) compared to patients without abscess in the univariate analyses. In addition, high-grade hepatic injury and transarterial embolization (TAE, p < 0.001) were also risk factors for liver abscess formation. Five factors (GOT, GPT, pH level in the arterial blood sample, TAE, and high-grade hepatic injury) were included in the multivariate analysis. TAE, high-grade hepatic injury, and GPT level were statistically significant. The odds ratios of TAE and high-grade hepatic injury were 15.41 and 16.08, respectively. A receiver operating characteristic (ROC) analysis was used for GPT, and it suggested cutoff values of 372.5 U/L. A prediction model based on the ROC analysis had 100 % sensitivity and 86.7 % specificity to predict liver abscess formation in patients with two of the three independent risk factors. CONCLUSIONS: TAE, high-grade hepatic injury, and a high GPT level are independent risk factors for liver abscess formation.

The influence of different movements on ambulatory blood pressure in hypertensive subacute stroke patients.

OBJECTIVE: This study evaluated variation in blood pressure (BP) in hypertensive subacute stroke patients performing eight different types of active movement, and variations in BP over time. METHODS: The study included 35 subacute stroke patients (60 - 74 years old) and 15 age-matched healthy volunteers. Ambulatory systolic and diastolic BP was measured over 4 consecutive days, before and during active movement. RESULTS: The greatest effect of the different active movements in stroke patients was on mean systolic BP variability (BPV). There was a significant difference in systolic and diastolic BPV between stroke patients at different time-points and compared with healthy volunteers. Systolic BPV during shifting from the ward to the rehabilitation centre was significantly higher than for all other active movements. Mean systolic BPVs during the sessions on the first and second days were significantly higher than for the sessions on the third and fourth days in stroke patients and compared with healthy volunteers. CONCLUSIONS: Systolic BP was found to be increased in hypertensive subacute stroke patients during their first and/or second attempts at performing active movements. Therapists should consider the BP of hypertensive subacute stroke patients during these first two attempts, especially for activities involving the patient moving from the ward to the rehabilitation centre.

Halysin, an antiplatelet Arg-Gly-Asp-containing snake venom peptide, as fibrinogen receptor antagonist.

By means of Sephadex G-75 and CM-Sephadex C-50 column chromatography and reverse-phase HPLC, a low molecular weight (Mr = 7500), cysteine-rich peptide, halysin, was purified from Agkistrodon halys (mamushi) snake venom. Halysin is a potent platelet aggregation inhibitor that concentration-dependently inhibited human platelet aggregation stimulated by ADP, thrombin and collagen (IC50 = 0.16 to 0.36 microM) without affecting platelet secretion. It was active in inhibiting platelet aggregation of platelet-rich plasma and whole blood. Halysin had no effect on thromboxane B2 formation of platelets or intracellular Ca2+ mobilization of Quin 2-AM loaded platelets stimulated by thrombin. It inhibited the fibrinogen-induced aggregation of elastase-treated platelets. Halysin concentration-dependently inhibited the 125I-fibrinogen binding to ADP-stimulated platelets in a competitive manner (IC50 = 0.16 microM). 125I-Halysin bound to resting platelets (Kd = 1.6 x 10(-7) M) and to ADP-stimulated platelets (Kd = 3.4 x 10(-8) M) in a saturable manner. EDTA, the Arg-Gly-Asp (RGD)-containing snake venom peptides trigamin and rhodostomin, Arg-Gly-Asp-Ser (RGDS), and Gly-Gln-Gln-His-His-Leu-Gly-Gly-Ala-Lys-Gln-Ala-Gly-Asp-Val blocked both 125I-fibrinogen binding and 125I-halysin binding to ADP-stimulated platelets. The monoclonal antibody, 7E3, raised against glycoprotein IIb-IIIa complex blocked both 125I-fibrinogen and 125I-halysin binding, whereas 10E5 had no significant effect on halysin binding to ADP-stimulated platelets, indicating that 7E3 and halysin bind to an epitope which is different from that of 10E5. RGDS concentration-dependently inhibited 125I-halysin binding in a competitive manner. We determined the primary structure of halysin which is a single peptide chain of 71 amino acid residues. An RGD sequence appeared in the carboxy-terminal domain of halysin. Halysin showed about an 85% identical sequence with trigamin which is a specific antagonist of fibrinogen receptor associated with glycoprotein IIb-IIIa complex. In conclusion, halysin inhibited platelet aggregation by interfering with fibrinogen binding to the fibrinogen receptor of the activated platelets. The RGD sequence of halysin plays an important role in the expression of its biological activity.

Edematous response caused by [Thi5,8,D-Phe7]bradykinin, a B2 receptor antagonist, is due to mast cell degranulation.

[Thi5,8,D-Phe7]bradykinin caused hind-paw edema and degranulation of isolated peritoneal mast cells in a dose-dependent manner. Pretreatment with diphenhydramine/methysergide or compound 48/80 completely suppressed the edematous response caused by [Thi5,8,D-Phe7]bradykinin, whereas bradykinin-induced hind-paw swelling was only partially inhibited by diphenhydramine and methysergide pretreatment; the residual response was significantly further depressed by [Thi5,8,D-Phe7]bradykinin. Neither the bradykinin- nor [Thi5,8,D-Phe7]bradykinin-induced edematous response was significantly affected by aspirin or BW755C. The mast cell degranulation caused by [Thi5,8,D-Phe7]bradykinin and bradykinin was inhibited by gangliosides but not by heparin. These results suggest that the edematous response elicited by [Thi5,8,D-Phe7]bradykinin was mainly due to the actions of mediators released by the degranulation of mast cells. Unlike bradykinin, [Thi5,8,D-Phe7]bradykinin was devoid of a direct exudation-promoting effect but exerted an antagonistic effect on the direct effect of kinin. If the influence of mast cells degranulation could be minimized, [Thi5,8,D-Phe7]bradykinin could be used as a tool to evaluate the role of kinin in the edematous response in inflammation.

Antiplatelet effect of butylidenephthalide.

Butylidenephthalide inhibited, in a dose-dependent manner, the aggregation and release reaction of washed rabbit platelets induced by collagen and arachidonic acid. Butylidenephthalide also inhibited slightly the platelet aggregation induced by PAF and ADP, but not that by thrombin or ionophore A23187. Thromboxane B2 formation caused by collagen, arachidonic acid, thrombin and ionophore A23187 was in each case markedly inhibited by butylidenephthalide. Butylidenephthalide inhibited the aggregation of ADP-refractory platelets, thrombin-degranulated platelets, chymotrypsin-treated platelets and platelets in the presence of creatine phosphate/creatine phosphokinase. Its inhibition of collagen-induced aggregation was more marked at lower Ca2+ concentrations in the medium. The aggregability of platelets inhibited by butylidenephthalide could be recovered after the washing of platelets. In human platelet-rich plasma, butylidenephthalide and indomethacin prevented the secondary aggregation and blocked ATP release from platelets induced by epinephrine. Prostaglandin E2 formed by the incubation of guinea-pig lung homogenate with arachidonic acid could be inhibited by butylidenephthalide, indomethacin and aspirin. It is concluded that the antiplatelet effect of butylidenephthalide is mainly due to an inhibitory effect on cyclo-oxygenase and may be due partly to interference with calcium mobilization.

Characterization of the anticoagulants from Taiwan cobra (Naja naja atra) snake venom.

Taiwan cobra (Naja naja atra) snake venom was separated into 19 fractions by means of CM-Sephadex C-50 column chromatography. Anticoagulant Fractions V-VII were refractionated by gel filtration on Sephadex G-50 and the purified component possessed phospholipase A2 activity and an inhibitory effect on collagen-induced platelet aggregation. The anticoagulant action could be antagonized by phospholipid or platelet factor 3. Anticoagulant Fraction XVII was also further refractionated by gel filtration on Sephadex G-50 and the purified component was shown to be cardiotoxin. It was a weak anticoagulant, caused direct hemolysis and potentiated collagen-induced platelet aggregation. Thromboelastographic studies showed that the anticoagulant action of cobra venom is due to the synergistic effects of phospholipase A2 and cardiotoxin.

Purification and characterization of a platelet aggregation inducer from Calloselasma rhodostoma (Malayan pit viper) snake venom.

A potent platelet aggregation inducer was purified from Calloselasma rhodostoma snake venom by Sephadex G-75, CM-Sephadex C-50 and Sephacryl S-300 column chromatography. It was homogeneous as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, with a molecular weight estimated to be 28,160 +/- 1280. It was devoid of phospholipase A2, fibrino(geno)lytic and thrombin-like activities. The venom inducer elicited platelet aggregation and the serotonin release reaction in rabbit platelet-rich plasma and platelet suspension. Exogenous calcium was required for its platelet activation. Creatine phosphate/creatine phosphokinase and indomethacin did not inhibit the venom inducer-induced aggregation and release reaction. Mepacrine and verapamil preferentially inhibited aggregation, while PGE1 completely blocked both aggregation and release reaction. It is concluded that the venom inducer activates platelets through the activation of endogenous phospholipase A2 or C, leading to intracellular calcium mobilization, but independent of the ADP release reaction or thromboxane A2 formation.

Action mechanism of the platelet aggregation inducer and inhibitor from Echis carinatus snake venom.

Platelet aggregation inducer and inhibitor were isolated from Echis carinatus snake venom. The venom inducer caused aggregation of washed rabbit platelets which could be inhibited completely by heparin or hirudin. The venom inducer also inhibited both the reversibility of platelet aggregation induced by ADP and the disaggregating effect of prostaglandin E1 on the aggregation induced by collagen in the presence of A23187, arachidonate, ADP and platelet-activating factor (PAF) with an IC50 of around 10 micrograms/ml. It did not inhibit the agglutination of formaldehyde-treated platelets induced by polylysine. In the presence of indomethacin or in ADP-refractory platelets or thrombin-degranulated platelets, the venom inhibitor further inhibited the collagen-induced aggregation. Fibrinogen antagonized competitively the inhibitory action of the venom inhibitor in collagen-induced aggregation. In chymotrypsin-treated platelets, the venom inhibitor abolished the aggregation induced by fibrinogen. It was concluded that the venom inducer caused platelet aggregation indirectly by the conversion of prothrombin to thrombin, while the venom inhibitor inhibited platelet aggregation by interfering with the interaction between fibrinogen and platelets.

Characterization of the platelet aggregation inducer and inhibitor from Echis carinatus snake venom.

Echis carinatus venom was separated into twenty fractions by means of ultrafiltration and CM-Sephadex C-50 column chromatography. Fraction II possessed inhibitory activity on the aggregation of washed rabbit platelets and fraction XII possessed the procoagulant and platelet aggregation-inducing activity. Both were further purified by gel filtration on a Sephacryl S-200 column. The purified aggregation inducer was a glycoprotein with procoagulant activity 10-12-times that of the crude venom. It possessed proteinase and amidase but was devoid of esterase activity. The molecular weight was 16 000, and it contained 8.7% of neutral sugar. The isoelectric point was pH 7.6. The purified aggregation inhibitor was a single peptide chain with a molecular weight of 6800 and contained 22.1% of neutral sugar. The isoelectric point was pH 4.8. It was devoid of any enzymatic activity of the crude venom. The IC50 was about 10 micrograms/ml on the thrombin-induced platelet aggregation. The inhibitory activity was fully retained after the treatment of the venom aggregation inhibitor with neuraminidase, but was completely destroyed by sodium metaperiodate. Upon heat treatment at 90 degrees C, the venom aggregation inhibitor was heat stable at pH 5.5 for 4 h, but was completely destroyed after 2 h at pH 8.9 and retained about 50% of its inhibitory activity of the control at pH 7.2 for 4 h. The venom aggregation inhibitor decreased the elasticity of the whole blood clot, and this effect was related to its inhibitory action on platelet aggregation instead of blood coagulation.