The effect of intramuscular stanozolol on fibrinolysis and blood lipids

The effects of a single 50 mg intramuscular injection of the anabolic steroid stanozolol (Stromba) on fibrinolysis, blood coagulation and lipids was evaluated in 12 healthy male volunteers. Significantly increased plasminogen activator levels (p < 0.05) was noted 24 hours following the injection and these remained elevated for one week. Plasminogen levels increased significantly by day two (p < 0.01) and remained elevated for three weeks. HDL cholesterol fell (p < 0.01) and both total and LDL cholesterol increased (p < 0.05) when measured one month post injection. Stanozolol appears to have therapeutic potential as an activator of the fibrinolytic system when given by intramuscular injection.     

The fibrinolytic response to stanozolol in normal subjects

The effect of stanozolol (17-β-hydroxy-17-methyl androstano {3.2,-c} pyrazole) has been studied on various components of the fibrinolytic and coagulation systems in normal adult subjects. Statistically significant increases in plasminogen activator activity, measured by the euglobulin clot lysis time, and plasma plasminogen were observed two days and ten days respectively after administration of stanozolol; these remained elevated throughout the study. Also, statistically significant reductions of plasma fibrinogen and a2 macroglobulin occurred within seven days of commencement of the drug and these changes persisted throughout the six week period of the trial. These changes, shown in normal individuals, indicate the potential value of stanozolol in clinical situations where fibrinolytic enhancement is considered beneficial.     

Protein C, an anticoagulant protein, is increased in healthy volunteers and surgical patients after treatment with stanozolol

On both oral and intramuscular administration, the anabolic steroid stanozolol was found to increase protein C antigen concentrations in circulating blood. In fourteen healthy young volunteers (who received stanozolol orally, dose 10 mg/day) the average increase was 1.5-1.6 times the normal concentrations after 3-6 weeks' treatment and was accompanied by more moderate increases in the other vitamin K-dependent factors II, IX and X to 1.4, 1.4 and 1.2 times their normal concentration respectively. However, there was no change in factor VII. In sixteen elderly surgical patients, intramuscular injection (50 mg) one day prior to surgery induced a moderate increase within 24 hours (to 1.11 times the pretreatment concentration) and seven days after operation (to 1.19 times), and reduced the postoperative fall in protein C. Stanozolol administration seems to be a promising pharmacological method for increasing anticoagulant protein C levels in congenital and acquired deficiencies.     

Relationship between preoperative status of the fibrinolytic system and occurrence of deep vein thrombosis after major abdominal surgery

This study comprised 50 patients subjected to major abdominal surgery, of which 13 developed deep vein thrombosis (DVT) according to the 125I-fibrinogen test. Plasma was sampled preoperatively, for the specific analysis of tissue plasminogen activator (t-PA) before and during venous occlusion. The recently described fast t-PA inhibitor and plasmin alpha 2-antiplasmin complex (PAP) were also measured. The result of the laboratory analyses were correlated to the development of DVT. From the data obtained it is concluded that the evaluation of t-PA release during venous occlusion is a poor predictive factor for the occurrence of DVT after major abdominal surgery. The level of the t-PA inhibitor appears to be raised in these patients, but the values obtained in this material were not related to the development of postoperative DVT. Patients with elevated PAP levels, as shown previously, have a lesser tendency to develop postoperative DVT.     

Aspirin response variability after major orthopedic surgery

Introduction

Variability in platelet response to aspirin has been reported in patients undergoing cardiac surgery but has rarely been described in other operative settings and its mechanism remains uncertain. We performed a prospective cohort study to investigate the variability in platelet response to aspirin and to explore its mechanism in patients undergoing major orthopedic surgery.

Materials and Methods

Twelve aspirin-treated patients undergoing elective hip or knee replacement were recruited. Once-daily aspirin was continued throughout the perioperative period. We measured platelet function using light transmission aggregation (LTA) in response to arachidonic acid (PL_AA) and serum thromboxane B₂ (TXB₂) at baseline (before surgery) as well as on days 1, 2, 3, 4, 5, 6, and 8 after surgery. We defined aspirin low response as a PL_AA > 20%.

Results

Six patients exhibited aspirin low response, which typically started on post-operative days 3 or 4; the remaining 6 patients had normal response to aspirin. Compared to aspirin responders, patients with aspirin low response showed significantly higher serum TXB₂ levels, a more pronounced early decrease in platelet count, and a significantly more rapid recovery of the platelet count after surgery.

Conclusion

Aspirin response variability occurred in patients after major orthopedic surgery, with one-half of the patients in our study exhibiting post-operative aspirin low response. Increased platelet turnover might be a contributor to aspirin response variability after orthopedic surgery.     

Increased fibrinolytic activity after surgery induced by low dose heparin

Forty women undergoing surgery under general anaesthesia for hyperplasia mammae were randomized to treatment with low dose heparin (5000 IU twice daily) or not. Preoperatively, and repeated on the 3. postoperative day, assays of euglobulin clot lysis time (ELT) after venous stasis, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) were performed. Compared to the control group heparin was found to give a significant rise in t-PA antigen before (24.0 vs. 11.2 ng/ml, p = 0.02), and especially after venous stasis (104.8 vs. 47.3 ng/ml, P = 0.007). t-PA activity was also significantly more increased after venous stasis in the heparin group than among the controls (4.2 vs. 1.4 U/ml, p = 0.04). This was also reflected in the ELT after venous stasis which was significantly shorter in the heparin group (p = 0.01). No differences in PAI were found between the groups. The present results point to a heparin-induced increase of t-PA synthesis in the endothelium, also giving rise to an increased level of circulating t-PA as measured immunologically. This effect of small dose heparin may play an important role in the prophylaxis against thrombo-emboli, in addition to the anticoagulant effect.     

Changes of the fibrinolytic system of animals induced by injection of tissue plasminogen activator

The changes in the fibrinolytic system of rats induced by repeated injections of tissue plasminogen activator (TPA) have been studied. The euglobulin fraction fibrinolytic activity increases 10 min after the first injection of TPA. Repeated injections of TPA for one or more days do not stimulate the fibrinolytic activity or TPA accumulation in the blood. Apparently in the absence of fibrin clots in the blood flow of healthy animals TPA is incapable of activating plasminogen conversion into plasmin. TPA, in its turn, is rapidly bound to the antiactivator and is excreted from the organism.     

A double-blind trial of intramuscular stanozolol in the prevention of postoperative deep vein thrombosis following elective abdominal surgery

Fibrinolytic shutdown may be important in the development of postoperative deep vein thrombosis (DVT). We have previously shown that stanozolol 50 mg, given intramuscularly 24 hr before surgery, prevents the decrease in plasminogen activator activity (PA) seen on the first postoperative day in patients at high risk of DVT. To investigate the role of fibrinolytic shutdown in causation of DVT, sixty patients were randomized in a double-blind controlled trial to receive stanozolol or placebo intramuscularly, and DVT was detected by leg scanning and confirmed by venography. Scan positive DVT occurred in 11 of 31 placebo patients (35%) and 12 of 29 who received stanozolol (41%). A significant decrease in PA was confirmed in the placebo group, while stanozolol caused a significant increase in PA on the first postoperative day. Patients in either group who did not develop DVT showed minimal changes in PA. We conclude that prevention of fibrinolytic shutdown by this regimen of stanozolol does not prevent postoperative DVT, and that further studies are required to clarify the relationship of postoperative fibrinolysis and DVT.     

Reduced fibrinolytic activity in coronary heart disease in basal conditions and after exercise

Fibrinolysis may be impaired in coronary heart disease patients. 20 coronary heart disease patients and 10 control subjects were examined for tissue-plasminogen activator activity, tissue-plasminogen activator antigen, fast tissue-plasminogen activator inhibitor and other fibrinolytic and haemostatic parameters including antigenic and functional protein C. Both patient and control groups were similar in age and smoking habits. All of these patients had a myocardial infarction between 1-3 months before this study. Assays were evaluated before and after an exercise test. Prothrombin time, activated partial thromboplastin time, protein C, plasminogen, alpha 2-antiplasmin, fibrinogen/fibrin degradation products and contact-activated fibrinolysis were similar before and after exercise in both groups. Fibrinolytic activity assayed by the euglobulin lysis time and fibrin-plate lysis methods was decreased in the patient group as compared with the control group but the difference was not significant. In basal conditions, tissue-plasminogen activator activity was defective in 50% of the coronary heart disease patients (p less than 0.01) and after exercise this percentage rose to 77% (p less than 0.01). However, tissue-plasminogen activator antigen in the coronary heart disease group was similar to that of the control group, both before and after exercise. The activity of the tissue-plasminogen activator inhibitor was persistently increased in coronary heart disease though this increase was not statistically significant. It is concluded that in coronary heart disease patients there is a defective fibrinolytic activity probably due to an increase in tissue-plasminogen activator inhibitor.     

Electric-foot-shock induced the supression of fibrinolytic activity in rats

Electric-foot-shock was given to rats to initiate constant mental stress and its effect on fibrinolytic activity was analyzed. After the termination of electric-foot-shock which was given for an hour, euglobulin clot lysis time in the stressed group significantly prolonged than those in the control group. tissue plasminogen activator activity was also significantly lower in the stressed group. These effects lasted at least for an hour and returned to the control values 24 hours after the stress. Whole blood serotonin levels, which mainly show serotonin contents in platelets, were higher in the stressed group. A negative correlation between whole blood serotonin and tPA activity in the stressed group was obtained. These results suggest that prolonged mental stress impairs fibrinolysis by decreasing tPA activity with a concomitant increase of serotonin contents in platelets.     

The fibrinolytic action of the synthetic agent S-1623 in a purified system of fibrin and plasminogen

The effects of the synthetic fibrinolytic agent α(isobutyl-4 cyclohexene-1 yl) propionic acid (S-1623) were investigated in a purified system. Bovine fibrin clots were incubated at 37°C with varying concentrations of S-1623 (0–10 mM) and a constant concentration of human plasminogen (1 μM). Two methods were used to measure lysis, e.g. visual observation of the clots and SDS-polyacrylamide gel electrophoresis. Plasmin formed during incubation was measured quantitatively by a spectrophotometric method using a chromogenic substrate. After 24 hours of incubation, a partial or total degradation of the clots was observed visually for S-1623 concentrations between 3 and 8 mM, with maximum degradation occuring at 4–5 mM. Analysis of the samples by acrylamide gel electrophoresis revealed total fibrinolysis at a concentration of 4–5 mM, partial fibrinolysis at 3 and 6–7 mM, and no fibrinolysis at other concentrations (0–2 mM and 8–10 mM). Proteolysis of plasminogen also occured, with maximum effect at 4–5 mM, and resulted in the production of fragments smaller than the intact plasmin molecule. The amidolytic activity coincided with the lytic concentrations of S-1623, with maximum activity occuring at 4–5 mM. No activity was observed in the absence of fibrin, plasminogen, or S-1623. Amidolytic activity was also generated, though to a lesser extent, when the fibrin substrate was replaced by fibrinogen. These results seem to show that the agent S-1623 is capable of generating plasmin-like activity in this system.     

Fibrinolytic activity in plasma and deep vein thrombosis after major abdominal surgery

In a prospective study of the frequency of deep vein thrombosis (DVT) in 45 patients subjected to major abdominal surgery, 17 patients showed signs of DVT as assessed by the ¹²⁵I-fibrinogen test. In 15 of the patients the DVT was diagnosed during the first four postoperative days. Blood samples were taken pre- and postoperatively and analysed for fibrinogen, prothrombin complex, APTT, platelet-count, plasminogen, α₂-antiplasmin, fibrin(ogen) degradation products, and plasmin-α₂-antiplasmin complex (PAP). The latter was used in order to reflect the fibrinolytic activity. Preoperatively, and postoperatively on day 3, the levels of PAP were significantly higher in patients without postoperative DVT. The data suggests that patients subjected to major abdominal surgery, who have enhanced fibrinolytic activity preoperatively, have a lesser tendency to develop postoperative DVT. Patients with postoperative DVT may have decreased fibrinolytic ability. From the data of the other parameters it is concluded that patients with DVT can have increased levels of FDP at the time of development of thrombosis.     

Marital status after epilepsy surgery

PURPOSE: To characterize features influencing marital status in a group of patients with refractory epilepsy before and after epilepsy surgery and to assess the effect of seizure control on marital status after epilepsy surgery. METHODS: We analyzed marital status in 430 epilepsy surgery patients and in a subset with temporal lobe epilepsy. Marital status was assessed in relation to gender and age of epilepsy onset and compared with marital rates for the U.S. population. Patients who had > or =4 years of postsurgical follow-up were examined for change in marital status after surgery. Those patients who changed marital status were then evaluated for change in employment. RESULTS: Marital rates were lower than expected in men. Men with onset of epilepsy by age 11 years were less likely to be married than men whose seizures began after age 11 or women whose seizures began at any age. Men and women with temporal lobe epilepsy had higher marriage rates than those with extratemporal lobe epilepsy. More than 4 years after epilepsy surgery (n = 190), patients who had no recurrent seizures were more likely to change marital status (28 of 124, 23%), than those who had recurrent seizures (five of 66, 8%). Seizure-free women were more likely to divorce (n = 9) than were seizure-free men (n = 1). Most men who married were employed (77%), whereas women who divorced were usually unemployed (67%). CONCLUSIONS: The age at which seizures begin influences later marital status in men, who have reduced marriage rates. The abolition of seizures by epilepsy surgery creates new opportunities for changing social relationships. Location of the epileptic focus may influence psychosocial function.     

Influence of detergents on the measurement of the fibrinolytic activity of plasminogen activators

The influence of detergents on the apparent activity of tissue plasminogen activator and of urokinase was investigated. The nonionic detergents Tween 80 and Triton X-100 and the zwitterionic detergent Zwitter-gent 314 caused a marked increase in the apparent activity of tissue plasminogen activator and, to a lesser degree, of urokinase in the fibrin plate assay, particularly at higher activator concentrations. These detergents did not enhance the plasma clot lysis in the presence of urokinase or tissue plasminogen activator. The anionic detergent sodium dodecyl sulfate had a small inhibitory action on the fibrin plate activity of urokinase and strongly inhibited the fibrin plate activity of tissue plasminogen activator. A systematic study into the mechanism of the stimulatory action of nonionic and zwitter-ionic detergents is presented.     

Biochemical markers for post-operative fatigue after major surgery

OBJECTIVE: To establish a link between tryptophan (a precursor for 5-hydroxytryptamine (5-HT) or serotonin, involved in sleep and fatigue) and post-operative fatigue after major surgery. BACKGROUND: There is a link between tryptophan (the precursor for the neurotransmitter 5-hydroxytryptamine), and its competitive binding with non-esterified fatty acids (NEFA) to albumin in the blood. An increase in the plasma concentration of free tryptophan can lead to an increased rate of synthesis of 5-HT in the brain. Free tryptophan competes with the branched chain amino acids (BCAA) for the same port of entry across the blood-brain barrier. It is suggested that the plasma concentration of these amino acids could be a marker of post-operative fatigue. In a previous study undertaken in this laboratory on patients undergoing two different types of major surgery, similar post-operative increases were observed in the plasma concentration of free tryptophan and the plasma concentration ratio of free tryptophan to branched chain amino acids. However, the study was retrospective and no measure of fatigue had been made. METHODS: In the present study, this deficiency has been addressed by administering a modified Profile of Mood States questionnaire to patients undergoing reconstructive or colorectal surgery. In addition, blood samples were measured for plasma free tryptophan, albumin, NEFA and branched chain amino acids before and on 2 days after surgery. RESULTS: There was a significant correlation between fatigue scores and plasma free tryptophan (P<0.000), and the plasma concentration ratio of free tryptophan/BCAA (P<0.016) after surgery in all the patients studied (n=34). This correlation was more marked in the colorectal-surgery patients, in whom surgery was more severe. In the three categories of patients receiving elective reconstructive surgery (n=24), those having breast reductions (n=6) had a lower plasma concentration of NEFA and appeared to recover from fatigue more quickly than those with pre-tibial lacerations or malignant melanoma. CONCLUSIONS: These data provide further evidence of a possible biochemical mechanism for central fatigue which involves a precursor of 5-HT. The provision of branched chain amino acids may help to combat the surge in free tryptophan that occurs during stress such as major surgery.     

成人心脏外科术后并发精神障碍31 例临床分析

目的提高对成人心脏外科手术后患者并发精神障碍认识与防治。方法分析620例成人心脏手术后出现精神障碍患者的临床表现和转归。结果本组并发精神障碍的发生率为5%(31/620),29例患者精神障碍治愈,2例死亡。结论长时间体外循环中脑血流灌注不足,微栓形成,术后并发心、肺、脑等脏器功能障碍及感染可能是精神障碍的诱发因素和出现精神障碍的主要原因。提高认识,及时有效地治疗躯体疾病及心理治疗,绝大多数患者预后良好。     

Abnormalities in the cellular phase of blood fibrinolytic activity in systemic lupus erythematosus and in venous thromboembolism

Fibrinolytic activities of whole blood and plasma were determined by ¹²⁵I-fibrin radiometric assay in 16 normal subjects, and in 11 patients with systemic lupus erythematosus (SLE), 14 with progressive systemic sclerosis (PSS), 23 with venous thromboembolic disease, and 20 patients awaiting elective surgery. Mean whole blood and plasma activities for patients with PSS ,and for those awaiting elective surgery, were similar to normal values, as was the mean plasma activity in patients with SLE. However, mean whole blood activity in SLE was significantly decreased compared with normals (p < 0.05), with mean plasma activity accounting for 44% of mean whole blood activity (compared with 17% in normal subjects), representing a 67% decrease in mean calculated cellular phase activity in SLE, when compared with normals. Since the numbers of cells (neutrophils, monocytes) possibly involved in cellular activity were not decreased, the findings suggest a functional defect in fibrinolytic activity of one or more blood cell types in SLE. An additional finding was the participation of the cellular phase as well as the well-known plasma phase of blood in the fibrinolytic response to thromboembolism.     

Neurologic complications after surgery for obesity

Bariatric surgical procedures are increasingly common. In this review, we characterize the neurologic complications of such procedures, including their mechanisms, frequency, and prognosis. Literature review yielded 50 case reports of 96 patients with neurologic symptoms after bariatric procedures. The most common presentations were peripheral neuropathy in 60 (62%) and encephalopathy in 30 (31%). Among the 60 patients with peripheral neuropathy, 40 (67%) had a polyneuropathy and 18 (30%) had mononeuropathies, which included 17 (94%) with meralgia paresthetica and 1 with foot drop. Neurologic emergencies including Wernicke's encephalopathy, rhabdomyolysis, and Guillain-Barré syndrome were also reported. In 18 surgical series reported between 1976 and 2004, 133 of 9996 patients (1.3%) were recognized to have neurologic complications (range: 0.08-16%). The only prospective study reported a neurologic complication rate of 4.6%, and a controlled retrospective study identified 16% of patients with peripheral neuropathy. There is evidence to suggest a role for inflammation or an immunologic mechanism in neuropathy after gastric bypass. Micronutrient deficiencies following gastric bypass were evaluated in 957 patients in 8 reports. A total of 236 (25%) had vitamin B(12) deficiency and 11 (1%) had thiamine deficiency. Routine monitoring of micronutrient levels and prompt recognition of neurological complications can reduce morbidity associated with these procedures.