Detection of monocyte tissue factor after endotoxin stimulation: comparison of one functional and three immunological methods.

Monocyte procoagulant activity is mainly due to tissue factor (TF) expression, but functional assays may not be sufficiently accurate in clinical use, making useful a determination of TF antigen level. The aim of this study was to compare the results of one functional and three immunological TF assays (ELISA, immunocytochemical staining on slides and flow immuno cytometric analysis), in normal monocytes, after standardized stimulation by endotoxin. TF expression was determined in blood mononuclear cells isolated by gradient centrifugation and cultured, with or without various concentrations of endotoxin. On lysed cells, TF activity was determined by amidolytic assay and TF antigen level was determined, after triton extraction, by ELISA (Imubind, American Diagnostica). Mouse monoclonal antibody against TF (4508, American Diagnostica) was used for 1) immunocytochemical (ICC) staining on cytocentrifuge slides (Avidine-Biotine-peroxidase-Complex revelation) and 2) flow cytometric analysis using indirect labeling (Fab'2 Fluoresceine Isothyocyanate revelation). The determination of TF activity and TF antigen by ELISA method were equally sensitive to low concentration of endotoxin (0.005 EU/ml) and well correlated in the presence of higher concentrations of endotoxin. ICC led to a qualitative detection with a similar sensitivity to endotoxin stimulation. Flow cytometric analysis was poorly sensitive to increasing stimulation of monocytes. Of note, the functional, ELISA and immunocytochemical assays for monocyte TF expression were sensitive to endotoxin concentrations as low as 0.005 EU/ml.

Homozygous variant of antithrombin with lack of affinity for heparin: management of severe thrombotic complications associated with intrauterine fetal demise.

Patients with homozygous heparin-binding-site (HBS) qualitative antithrombin deficiencies are at significant risk of venous and arterial thrombosis. We report on the eighth case of homozygous HBS deficiency, and the fourth case concerning the Arg 47-Cys mutation. The proposita is a 25 year old, without known thrombotic antecedent, despite an oral contraceptive therapy for 7 years. After 25 weeks of a first pregnancy, she presented an intrauterine fetal demise complicated with deep vein thrombosis and pulmonary embolism. Heparin therapy was inefficient (no clinical nor angiographic improvement, no biological hypocoagulability). Heparin cofactor activity was < 10%, antigen concentration was normal. The crossed immunoelectrophoresis of patient's plasma, with and without heparin, showed a typical profile of qualitative HBS antithrombin deficiency. The molecular analysis revealed an homozygous Arg 4-Cys mutation. Antithrombotic therapy was achieved with continuous infusion of antithrombin concentrates (80 IU/kg/day) and unfractionated heparin (500 IU/kg/day) during 12 days, leading to clinical improvement, and followed by treatment with vitamin K antagonists. This observation emphasizes the risk of intrauterine fetal demise and the inefficiency of heparin therapy without antithrombin infusion in type II HBS homozygous deficiency. The management of a future pregnancy will probably require repeated infusions of antithrombin.

Treatment of lymphorrhea with exposed or infected vascular prosthetic grafts in the groin using sartorius myoplasty.

Thirteen myoplasties using the sartorius muscle were performed on 12 patients from 1980 to 1985 for "healing problems" in the groin with subjacent synthetic grafts. Persistant aseptic lymphorrhea was the indication for 4 patients. In 3 other cases, bacterial cultures from the wound were positive. In 2 other patients there was clinical evidence of sepsis with purulent discharge from the wound and an exposed graft. In 3 cases myoplasty was used as a preventive measure after reoperation on patients in poor general condition. Follow-up extends from 3 to 54 months. There was only one recurrence observed at 19 months which was successfully treated by segmental resection of the infected graft and insertion of a new prosthesis through the obturator canal. No recurrence was observed among the other patients as judged by clinical observation and biological tests for inflammation, echotomography, CT scan and indium scintigraphy. The treatment of choice for an infected prosthesis should be removal of the graft and extra-anatomic bypass in the majority of cases. However in some situations, excision of the wound and myoplasty using the sartorius muscle may be of some value and needs further evaluation.

The place of cardiac denervation in the surgical treatment of Prinzmetal variant angina.

Coronary artery spasm has been described as occurring frequently in Prinzmetal variant angina. The relatively poorer results obtained after aorto-coronary by pass grafting carried out in patients with Prinzmetal angina may be due to recurrence of spasm despite the grafts. Accordingly it has been our recent policy since February 1973 to carry out cardiac denervation in all patients with Prinzmetal variant angina. The patients fall into two groups depending on the presence or absence of organic disease in the coronary vessel. The technique of cardiac denervation (plexectomy) as described by Arnulf is fully described and the early and late results of this procedure in the two groups are documented and discussed.

Chronic traumatic aneurysms of the descending thoracic aorta (19 cases).

From 1973 through 1983, 19 cases of chronic traumatic aneurysms (CTA) were observed. Initial trauma was well documented in every case. Patients mean age at time of trauma was 22; mean age at time of surgery was 34. Sixty per cent of patients had no apparent thoracic injury at time of trauma. Ninety-five per cent had associated injuries. Ten/nineteen were asymptomatic. Eighteen were operated on. Rupture was complete in 11, partial in 7. One of the partial ruptures was a simple scar on the aorta. Eighteen were located at the site of the aortic isthmus, one was at level T8-T9. Seventeen had a prosthetic dacron graft sutured from inside the aneurysm. The case where a simple scar was found had a dacron wrapping. Spinal cord protection was used in all cases except in one who was already paraplegic preoperatively. Various shunts were used in 12 cases; 1 patient in the by-pass group had paraplegia. CTA is not a benign disease and all cases, even asymptomatic, should be operated on with a very low risk of mortality (0/18). Occurrence of paraplegia still remains a possible complication although the risk of spinal cord ischemia seems lower than in arteriosclerotic dissecting aneurysms. We favour the "old" technique of temporary dacron shunt graft in CTA for simplicity and easy assessment of function ot the shunt.

[Short- and mean results of mitral and aortic valve replacement with a Björk-Shiley disc prosthesis. Thromboembolic and hemorrhagic complications]. / Résultats à court et moyen terme du remplacement valvulaire mitral et aortique par prothèse à disque de Björk-Shiley. Les accidents thrombo-emboliques et hémorragiques.

96 patients with a Björk aortic valve and 112 patients with a Björk mitral valve were followed up for four and a half years and five years after operation respectively. The actuarial survival rate was 82.5% in the aortic and 73% in the mitral patients. Late death was observed in 7.3% of mitral patients with thromboembolic complications and 4.2% of mitral patients with left ventricular dysfunction, compared to 2.6% of aortic patients with thromboembolism and 3.6% with left ventricular dysfunction. The incidence of thrombolic complications was three times as great with the prosthesis in the mitral position. The probability of absence of thromboembolic complications, studied by actuarial methods, was 93% at 4 1/2 years in aortic prostheses compared to 82% at 5 years in the mitral prostheses. 12 haemorrhagic complications (5.7%), with one fatality, were observed. Aortic valve replacement with a Björk prosthesis is a very satisfactory operation and the results compare favourably with other prostheses. However, the risk of thromboembolic complications should be seriously considered in the surgical indications when this prosthesis is to be used for mitral valve replacement.

[Surgery of acquired heart valve diseases in France: developments in a 10-year period. A multicentric study]. / Evolution en 10 ans des valvulopathies acquises opérées en France. Etude multicentrique.

A multicenter study compares the surgery of acquired valvular diseases in France in 1974 and 1984. This study concerns etiology, surgical procedures and postoperative results within 3 months after operation. 2718 observations issued from 20 medical and surgical centers are divided in 2 groups: the first includes 856 patients who underwent surgical operation in 1974, the other group with 1862 patients was operated on in 1984. Significant differences may be observed. The mean age is higher in 1984 (55 vs. 47 years); the rheumatismal etiology decreases from 50.2% in 1974 to 35.1% in 1984; the degenerative and dystrophic causes increase from 13.8% in 1974 to 32.9% in 1984; while the monovalvular mitral lesion is more frequent (42%) than the aortic one (32.7%) in 1974, the proportion is reversed in 1984 where 47% aortic and 34.5% mitral lesions are found; the number of surgical treatments of mitral stenoses in 1984 is half of those in 1974, but the number of surgically treated aortic stenoses and mitral regurgitations is double of those in 1974; the preoperative examination includes left-side heart catheterization in 81.1% and coronary angiography in 64% of surgically treated patients en 1984, the respective percentages en 1974 being 57.8% and 16.1%. In 1974, 27.6% of patients are in a preoperative functional stage I or II, in contrast to 42.8% in 1984. Mitral commissurotomy represents 29.3% of mitral surgery in 1974 (25.6% of them with closed operation), the respective percentage in 1984 being only 10.5% (2.5% of them with closed heart operation).(ABSTRACT TRUNCATED AT 250 WORDS)

[Value of vasodilators in decreasing the afterload during infrarenal abdominal aorta cross-clamping]. / Intérêt des vasodilatateurs pour diminuer la post-charge au cours du clampage aorto-abdominal sous-rénal.

Adverse effects of aortic crossclamping (A. C. C.) have been shown by a retrospective study and a literature review. A. C. C. results in increased afterload with ensuing left ventricular function alteration and low cardiac index (C. I.). 15 P. T. S. sustaining an operation with A. C. C. below the renal arteries were studied. A Swan-Ganz catheter was positioned with recording of pressures, including radial artery pressure and repeated cardiac output determinations. Prior to A. C. C., vascular filling and nitroprusside (N. P.) infusion improved hemodynamic conditions. Increase of C. I. (1.8 to 2.8 l/mm-1/m2) was observed with important decrease in peripheral vascular resistance (from 2,346 to 1,425 dyne/s-1/cm-5), pulmonary capillary pressure was lowered slightly and heart rate as well as mean arterial pressure remained stable. During A. C. C., rate of N. P. infusion was increased to maintain stable arterial pressure. Hemodynamic improvement observed prior to A. C. C. was maintained.

[The long term results of reparative surgery for aorto-iliac stenosis and chronic obstruction. 563 cases followed up for 2 to 13 years (author's transl)]. / Résultats a long terme de la chirurgie restauratrice des sténoses et oblitérations chroniques aorto-iliaques. A propos de 563 cas suivis de 2 à 13 ans.

The results of surgery for aorto-iliac obliterative arterial disease deteriorate progressively over 10 years to leave only 44% good results, 39% deaths, 3% poor results and 14% amputations. Nevertheless, the quality of the surviving patients is satisfactory with 72% good functional results at 10 years and a permeability rate of 76% of reparative procedures at the same period. It is certain that current improvements having resulted in a decrease in early mortality will affect the long-term results in view of the tendency to horizontalisation of graphs beyond the first six months.

[G20210A transition in the prothrombin gene and venous thromboembolic disease]. / La transition G20210A dans le gène de la prothrombine et la maladie thromboembolique veineuse.

INTRODUCTION: Genetic predisposition to venous thrombosis can be due to coagulation inhibitor deficiencies (antithrombin, protein C or protein S) or to activated protein C resistance resulting from factor V Leiden mutation (FV Leiden). Poort et al. recently identified a new polymorphism in the 3'-untranslated region of the prothrombin gene, the G20210A transition (FII G20210A), which was found to be associated with an increased risk of venous thrombosis. EXEGESIS: The prevalence of the A allele is approximately 1 to 4% in the general population, and 5 to 7% in patients with venous thrombosis. Heterozygous carriers have a three to five times increased risk of thrombosis. The diagnosis is based on a polymerase chain reaction technique and restriction enzyme digestion from genomic DNA. Recent studies aim to determine the relative risk of thrombosis and the clinical features which are associated with the mutation (age of first thrombosis, recurrence). The thrombotic risk seems to be higher when FII G20210A transition is associated with the FV Leiden mutation. CONCLUSION: The presence of heterozygous FII G20210A transition does not modify the management of acute thrombotic events but can lead to an increase in the duration of the anticoagulant treatment. When such a genetic abnormality is identified, thorough information of the patient is needed, including on the prophylactic heparin in high-risk situations and caution on the prescription of oral contraceptives containing estrogens.

[Inhibitors of factor VIII in non-hemophilic patients. Biological and therapeutic aspects. Apropos of 3 cases]. / Les inhibiteurs du facteur VIII chez le sujet non hémophile. Aspects biologiques et thérapeutiques. A propos de 3 observations.

A coagulation inhibitor of the anti-factor VIII: C type was detected in three non-haemophilic male patients aged 75, 70 and 52 respectively. In all three patients antibody titres were low (less than 12.5 Bethesda units initially, less than 20 units subsequently), and a low but detectable level of factor VIII: C persisted (7 to 12 p. 100 in two patients who had severe haemorrhages and 2.100 in the third one). The 3 inhibitors inactivated factor VIII: C with a complex, type II kinetics (Biggs et al.). Strong doses of anti-haemophilic A fractions were biologically effective in one patient but could not stop severe bleeding. Activated plasma fractions were used successfully on several occasions. Once, moderate and repeated doses of anti-haemophilic A fractions resulted in satisfactory correction of factor VIII: C level, and a minor surgical operation could be performed. An immunosuppressive treatment was administered for 3 weeks to one patient and for 3 months to the other two patients. In all three cases the inhibitor disappeared after 5 to 8 months. In non-haemophilic patients with factor VII: C inhibitor the treatment of haemorrhagic episodes must take into account the severity of bleeding, then the usually complex kinetics of the inhibitor; thus it cannot be a direct copy of the treatment used in haemophiliacs with type I inhibitors.

[Durability of the Carpentier-Edwards porcine bioprosthesis in aortic or mitral positions. 10 years' results on 458 surgically treated cases]. / La durabilité des bioprothèses porcines de Carpentier-Edwards en position aortique ou mitrale. Résultats à dix ans sur 458 opérés.

458 patients with a Carpentier-Edwards porcine bioprosthesis (aortic (Ao): 169, mitral (Mi): 289) operated between January 1975 and December 1981, were studied during the first trimester of 1987. Forty seven patients underwent an associated operation. The total follow-up was 3,001 patient-years with a maximum follow-up of 11.4 years and a mean follow-up of 6.5 years. Only 5.6% of patients were lost to follow-up. The patients were aged between 20 and 80 years. The actuarial 9-year survival rate was 69.2 +/- 6.3% for aortic prostheses and 79.6 +/- 3.9% for mitral prostheses. The principal cause of valve failure, appearing with a considerable frequency after 5 years, was primary tissue degeneration which alone represented 67.8% of the causes of valve failure. The rate of absence of valve failure, for all causes combined, was 77.8 +/- 5.9% for the aortic position and 74.9 +/- 4.9% for the mitral position. The actuarial rate of absence of primary tissue degeneration at 9 years was 79.7 +/- 4.1% for aortic prostheses and 75.2 +/- 4.4% for mitral prostheses. The frequency of tissue degeneration decreased with increasing age, representing 2.9%, 1.9% and 1.5% patient-years respectively for the age-groups: 20 to 39 years, 40 to 59 years and 60 to 80 years. However, this difference was not statistically significant. Tissue degeneration was the principal cause for reoperation (n = 59) with an operative mortality of 7.8%.

[Use of intraluminal dilatation catheters in the surgical treatment of pulmonary atresia with intact septum]. / Utilisation des cathéters à dilatation endoluminale dans le traitement chirurgical de l'atrésie pulmonaire à septum intact.

Despite considerable progress in surgery and intensive care and the advent of prostaglandins, pulmonary atresia with intact ventricular septum remains a severe heart disease. The authors describe a technique of pulmonary valve plasty across the right ventricule, using dilatation balloon catheters for peripheral arteries. This technique proved successful after a 4 to 12 months follow-up in 2 out of 4 neonates who underwent surgery. It is fast, causes little damage to the right ventricle and could be improved by using catheters specifically designed for this type of surgery.

[Hematologic changes induced by extracorporeal circulation]. / Modifications hématologiques induites par la circulation extracorporelle.

The plasma and cellular changes seen during the use of extracorporeal circulatory circuits define the system's degree of haemocompatibility. Heparin is still very much used to prevent activation of the blood clotting mechanisms and to reduce their effects. The fall in concentration of the clotting factors and their inhibitors is usually moderate; it is due to haemodilution, particularly important in cardiac surgery and during plasma exchanges. Fibrinolysis is often activated. In cardiac surgery, it is seen in nearly 20% of cases straight after the end of the ECC, and in nearly 80% of cases during the ECC. In all cases of resin haemoperfusion, there is an early transitory fibrinolytic burst, seen only rarely during haemodialysis and plasma exchanges. This phenomenon is usually well controlled by the natural inhibitors; it can be prevented by antifibrinolytic drugs. Cellular changes show the same trends during cardiac surgery, haemoperfusion and haemodialysis. Thrombopaenia is seen within a few minutes starting of ECC. It is caused by platelet activation, with aggregate formation; these are then trapped by the microcirculation. Leukopaenia occurs at the same time, later followed by rebound; complement activation could be the main cause by forming aggregates of polymorphonuclear cells and monocytes. Intravascular mechanical haemolysis reaches significant levels only in a few cardiac surgical procedures. The great speed of activation of the plasma and platelet enzyme systems by the ECC circuits explains these early changes. They are not only due to direct effects of the physiological circulatory characteristics and to contact with artificial surfaces, but also to plasma-cell interactions and to the patients' reaction to these first alterations.

[Successes and failures of the activated partial thromboplastin time in the preoperative evaluation]. / Heurs et malheurs du temps de céphaline activée dans le bilan préopératoire.

In a prospective study assessing haemostatic functions, the activated partial thromboplastin time was prolonged in 134 out of 10,229 patients studied, without an increase in the prothrombin or thrombin times; this abnormality persisted in only 37 of them on a new blood sample. A retrospective analysis was made of 265 patients who had such an isolated prolongation of the activated partial thromboplastin time on two successive blood samples: the causal abnormality remained unexplained in 135 patients; a well defined coagulation disorder without abnormal bleeding tendency was present in 110 patients (1 severe factor XII deficiency, 58 partial factor XI or XII deficiencies and 51 lupus anticoagulants); a bleeding disorder was diagnosed in 20 patients (8 haemophilias, 8 Von Willebrand's diseases, 4 factor VIII inhibitors). The well-iron efficacy of the activated partial thromboplastin time for detecting coagulation abnormalities is counter-balanced by some disadvantages such as the delay for biologic conclusions. In the preoperative assessment of haemostatic functions, rather than taking a routine approach, it would seem better to determine for each patient the need and the extent of biological testing according to the type of planned surgery, the clinical status of the patient and possible bleeding symptoms.

[Prosthetic duplication of the ascending aorta]. / Duplication prothétique de l'aorte ascendante.

A simple implantation technique for multiple bypass of the ascending aorta with cervico-encephalic and infradiaphragmatic targets is reported. A conduit made by termino-terminal suture of two bifurcated grafts is anastomosed latero-laterally to the ascending aorta. The procedure is easy to perform and provides a suitable trajectory to the grafts.

[Mediastinal pseudo-tumor from portal hypertension (author's transl)]. / Pseudo-tumeur du médiastin par hypertension porte.

A radiological opacity of the posterior and inferior mediastinum should evoke a lesion of vascular origin. The venous nature of the mass can be easily confirmed by morphological changes apparent during the respiratory cycle and changes in position. Investigations to establish etiology of this venous ectasia arising from the azygos vein require more extensive radiological examinations, and computed tomography may be of value. Portal hypertension is one cause of increased venous blood flow in the azygos systems, and should be systematically considered.