Prognostic significance of antithrombin III, plasminogen and proactivator of plasminogen activity in viral hepatitis

Antithrombin III/AT III/, plasminogen (Plg) and proactivator of plasminogen [PPlg] activity were studied in 663 patients with various liver diseases and 547 healthy subjects. Parallel analysis of AT III, Plg and PPlg gives a very valuable prognostic information concerning the forthcoming evolution of viral hepatitis [v.h] and acute liver failure. The prognosis of v.h. in the cases with normal Plg activity is independent from the AT III activity in 98% of the cases it is associated with clinical improvement. The combination with low Plg and elevated AT III activity suggested clinical improvement in 65-90% of the patients. Most critical is the combination between low Plg and low AT III activity. This combination suggests clinical aggravation and danger of hepatic coma. The existence of 4 patterns of AT III activity is shown: elevated, normal in physiological condition, normal in pathological condition and decreased activity.     

Antithrombin III. Physiologic, physiopathologic and laboratory aspects]

Hemostatic control is based in a delicate balance between the activities of activator enzymes and their inhibitors, each one depending on a large number of proteins. Plasma Antithrombin III (ATIII) is one of the most important coagulation inhibitors and the fundamental enzyme for the therapeutical action of heparin. In the last years it was well established that ATIII deficiency accounts for a thrombotic state and inefficiency of heparin therapy. In this work, the authors review the biology of ATIII including its biochemical nature, its physiology, physiopathology and mechanism of action, analysing the implications of its deficiency. The authors draw the attention on clinical and laboratory studies that analyse the prevalence and importance of congenital and acquired deficiency of ATIII, in relation to the prevalence of venous thrombosis. Finally, the laboratory methods applied to the study of ATIII and to the biological control of heparin therapy are described with emphasis on the importance of the ATIII concentrates on this type of treatment. Also the fundamental aspects of heparin resistance are specially mentioned.     

Antithrombin III, Antifactor Xa and Heparin

Methods have been devised for the measurement of antithrombin and of the natural inhibitor of activated factor X.
The relation between heparin and its plasma cofactor and the destruction of thrombin and activated factor X were studied. As observed by other workers, heparin has more effect on the speed of thrombin neutralized than on the amount neutralized after 1 hr of incubation. When the neutralization of activated factor X was studied it was found that heparin at very low concentrations, with a plasma cofactor, promoted the progressive destruction of activated factor X.     

Methods for determination of plasmin, antiplasmin and plasminogen by means of substrate S-2251.

The chromogenic substrate S-2251 (H-D-Val-Leu-Lys-pNA), a selective and sensitive substrate for plasmin activity, has made it possible to develop simple and reproducible methods for the determination of antiplasmin and plasminogen in human plasma. These methods have been optimized and studied in detail and found to be very specific for the respective factors.     

Primary ventricular fibrillation. Clinical features and prognostic significance

The objective of this study was to evaluate the clinic conditions and the prognosis of patients with primary ventricular fibrillation (PVF) as complication of acute myocardial infarction. We retrospectively analyzed 1,120 patients admitted in Coronary Care Unit within 12 hours of onset of symptoms. PVF (not associated with significative heart failure or shock and occurred within 48 hours of onset of symptoms) occurred in 62 patients (5.53%). The frequency of PVF was highest in patients admitted in the first hours after infarction (p = 0.01) and the inferior localization (p = 0.001). Cigarette smoking was identified as strong independent risk factor for ventricular fibrillation (p = 0.009; relative risk 1.945). A statistically significant excess of pericarditis (p = 0.002), ventricular tachycardia (p = 0.004), atrioventricular block (second-third degree) (p = 0.001) and moderate degree of heart failure (p = 0.003), was found in patients with PVF. The occurrence of PVF was not associated to a significantly higher in hospital mortality rate than that observed in reference group (without ventricular fibrillation) (12.90 vs 14.36%). In the long-term survival at 5 years in patients with PVF, who are discharged alive, was 87.82% vs 80.58% in control group. We conclude: 1. Patients with PVF had more complications rate than among those without it. 2. PVF isn't a marker of increase in hospital death rate. 3. PVF by itself does not indicate an adverse long-term prognosis.     

The Determination of Antithrombin III by Radioimmunoassay and its Clinical Application

A radioimmunoassay (RIA) had been developed for the determination of antithrombin III (AT III) in man. The detection limit was 25 microgram/dl. AT III-RIA level and biological activity (anti-Xa) was significantly correlated (r = 0.737, P less than 0.001). Plasma levels in 36 healthy males (mean +/- SD, 19.9 +/- 2.5 mg/dl) and 21 healthy females (19.1 +/- 2.4 mg/dl) were similar. Serial AT III measurements in normal menstruating females showed lower levels during midcycle and higher concentrations during menstruation. In carcinomas, the AT III levels were lower than normal, particularly in hepatocellular carcinoma. In cirrhosis of liver, the levels were markedly decreased and in some patients were below that found in congenital AT III deficiency. Patients with deep vein thrombosis and patients with heart valve replacement had lower levels than normal, while patients with cerebral vascular occlusion had normal levels. The possible use of AT III as a diagnostic tool of post-operative deep vein thrombosis was demonstrated in one patient after hysterectomy. The increased sensitivity, specificity and precision of this type of assay offer distinct advantages over existing methods of AT III estimation.     

Protein C,Protein S,and Antithrombin III Deficiencies

Journal of Thrombosis and Thrombolysis -     

Cardiac dysrhythmia following pneumonectomy. Clinical correlates and prognostic significance

Cardiac tachydysrhythmias occurred in 53 (22 percent) of 236 consecutive patients undergoing pneumonectomy. All patients had preoperative electrocardiograms which showed normal sinus rhythm. Patients did not receive digitalis before surgery. Atrial fibrillation was the most common dysrhythmia (64 percent; 34/53), followed by supraventricular tachycardia (23 percent; 12/53) and atrial flutter (13 percent; 7/53). No episodes of ventricular tachycardia were documented. Elevated concentrations of cardiac enzymes were associated with 12 (28 percent) of 43 tachydysrhythmias. Recurrent or persistent dysrhythmias were documented in 29 (55 percent) of 53 patients despite medical management or electrocardioversion (or both). Thirty-one percent (9/29) of these patients subsequently died during their hospitalization. There was no correlation between standard preoperative pulmonary function tests and the incidence of postoperative dysrhythmia. In addition, there was no correlation of dysrhythmia with postoperative diagnoses, surgical staging for lung cancer, postoperative arterial blood gas levels, or the fact that a completion pneumonectomy or chest wall resection was undertaken. An increased incidence of tachydysrhythmia was noted in patients undergoing intrapericardial dissections and those who developed postoperative interstitial or perihilar pulmonary edema. Twenty-five percent (13) of the patients experiencing tachydysrhythmias died within 30 days following their pneumonectomy. We conclude that tachydysrhythmias after pneumonectomy are associated with significant mortality, have poor correlation to preoperative pulmonary function, and occur more frequently following intrapericardial dissection and in patients who develop postoperative interstitial pulmonary edema or perihilar pulmonary edema.     

CD151、c-Met及整合素α3、α6在胰腺导管腺癌中的表达及其与预后的关系

目的 探讨CD151、c-Met和整合紊α3、α6蛋白在胰腺导管腺癌中的表达及其与预后的关系.方法 用免疫组化法检测71例胰腺导管腺癌及10例正常胰腺组织中CD151、c-Met和整合素α3、α6蛋白的表达,分析它们与临床病理特征及患者预后的关系.结果 CD151、c-Met和整合素α3、α6在71例胰腺导管腺癌组织中的表达阳性率分别为81.69%(58/71)、69.01%(49/71)、69.01%(49/71)和84.51%(60/71),而正常胰腺组织均未表达.CD151和c-Met的表达与肿瘤的TNM分期、淋巴结转移显著相关(P值均<0.05).CD151的表达与c-Met及整合素α3、α6的表达呈正相关(r=0.583,P=0.000;r=0.457;P=0.000;r=0.671;P=0.000).单因素分析显示,CD151、c-Met、整合素α3和α6的表达与预后有关(P值均<0.05).多因素分析表明,CD151、c-Met是患者术后生存时间的独立预后因子.结论 CD151、c-Met及整合素α3、α6在胰腺癌的发展、转移及预后发挥重要作用,CD151、c-Met可考虑作为临床评价胰腺癌生物学行为及评估预后的指标.     

Interrelations between ABO blood group, plasminogen, alpha1-antitrypsin, alpha2-macroglobulin and the platelet count in blood donors.

The level of plasminogen alpha1-antitrypsin, alpha2-macroglobulin and the platelet count were measured in 511 blood donors. The mean level of alpha1-antitrypsin was significantly lower in men of group B compared with that of group O. No other differences between the blood groups reached statistical significance. Woman had higher mean levels of alpha1-antitrypsin and alpha2-macroglobulin and a higher platelet count than men. The levels of plasminogen and alpha1-antitrypsin were significantly higher in women using oral contraceptive compared with those who were not. The level of alpha2-marcoglobulin fell with age until the 60-64 year age-group in men and the 40-49 year age-group in women. A positive correlation existed between the alpha1-antitrypsin and the alpha2-macroglobulin level and between the platelet count and the plasminogen level.     

Clinical and pharmacological significance of alpha2-adrenoceptor polymorphisms in cardiovascular diseases

The alpha2-adrenoceptors (alpha2-ARs) are receptors for endogenous catecholamines (norepinephrine and epinephrine) that mediate a number of physiological and pharmacological responses such as hypotension and sedation. Three distinct subtypes, denoted alpha2A-, alpha2B- and alpha2C-AR, have been characterized and cloned. Employment of mutation screening in the study of human populations from various ethnic backgrounds has shown that alpha2-AR genes are polymorphic. The functional and biochemical consequences of these polymorphisms have been analyzed by expressing the wild-type receptors and their respective genetic variants in heterologous systems such as CHO and COS-7 cells. Changes include alteration in G-protein coupling and in agonist-promoted receptor phosphorylation and desensitization. Case-control and population-based studies have shown clinical association with cardiovascular risk. Further investigation of the genetic variants in specialized cells and transgenic animals will provide the molecular basis of cardiovascular disease and may reveal alpha2-AR variants as potential targets for selective pharmacological interventions.     

Severe Antithrombin III Deficiency in a Patient with Pre-Eclampsia.

Severe acquired antithrombin III (AT III) deficiency was observed in a patient with severe pre-eclamptic toxaemia. Plasma AT III concentration of 0.25 U/ml was found in both functional and immunological assays. The patient was treated with human AT III concentrate as a result of the development of progressive disseminated intravascular coagulation (DIC), the further deterioration of renal function, the risk for thromboembolic complications and the possible adverse effects of heparin therapy. The selective correction of AT III activity resulted in a rapid disappearance of coagulation abnormalities. The patient underwent uncomplicated caesarian section. This observation indicates that acquired severe AT III deficiency may occur as an early feature of DIC in severe pre-eclamptic toxaemia.     

CDl51、c-Met及整合素仪α3、α6在胰腺导管腺癌中的表达及其与预后的关系

目的探讨CD蚓、c-Met和整合素仪3、拍蛋白在胰腺导管腺癌中的表达及其与预后的关系。方法用免疫组化法检测71例胰腺导管腺癌及10例正常胰腺组织中CD151、c-Met和整合素仪3、嘶蛋白的表达,分析它们与临床病理特征及患者预后的关系。结果CD151、c-Met和整合素仪3、面在71例胰腺导管腺癌组织中的表达阳性率分别为81．69％（58／71）、69．01％（49／71）、69．01％（49／71）和84．51％（60／71）,而正常胰腺组织均未表达。CD151和c-Met的表达与肿瘤的TNM分期、淋巴结转移显著相关（P值均〈0．05）。CD151,的表达与c-Met及整合素α3、α6的表达呈正相关（r=0．583,P=0．000;r=0．457;P=0．000;r=0．671;P=0．000）。单因素分析显示,CD151、c-Met、整合素α3和α6的表达与预后有关（P值均〈0．05）。多因素分析表明,CD151、c-Met是患者术后生存时间的独立预后因子。结论CD151、c-Met及整合素α3、α6在胰腺癌的发展、转移及预后发挥重要作用,CD151、c-Met可考虑作为临床评价胰腺癌生物学行为及评估预后的指标。     

Clinical significance of hepatic dysfunction with jaundice in typhoid fever

A retrospective case note review was undertaken to assess the clinical significance of hepatic dysfunction with jaundice in typhoid fever. Of the 57 patients, 21 (36.8%) had jaundice, while 36 (63.2%) did not have jaundice. Significantly higher proportions of jaundiced patients were females (P = 0.04). Confusion (P = 0.01), upper abdominal pain (P = 0.02), right upper quadrant tenderness (P = 0.0001), and low prothrombin index (P = 0.04) were statistically significant occurrences in jaundiced patients on admission. Admission mean values of serum bilirubin (P = 0.0001), gamma-glutamyltranspeptidase (GGT; P = 0.009), and alanine aminotransferase (ALT; P = 0.0005) were significantly higher in icteric patients while mean values of total serum protein (P = 0.0009) and albumin (P = 0.0001) were significantly higher in anicteric patients. There were no deaths. Glomerulonephritis occurred significantly (P = 0.001) more frequently in icteric patients. It is concluded that hepatic dysfunction with jaundice in typhoid fever indicates more severe hepatic injury, which may precipitate the development of clinically detectable glomerulonephritis.