Prognostic et traitement de l'endocardite bacterienne. Revue de 70 cas

The long term results of medical and surgical treatments have been reviewed in 70 cases examined during the last 8 years. In 24 of them, bacterial endocarditis developed after valvular replacement. Antibiotic treatment was administered during at least 6 weeks. Determinations of the minimum inhibitory concentration of the antibiotic and of the bactericidal power of the serum were considered as the most important laboratory controls. In the post-operative cases with prosthetic valves, numerous pathogenic organisms were found, including gram (minus) bacilli and monilia, which may partly account for the high mortality in this group. Despite surgical reinterventions, 20 of the 24 patients died. For the gram (+) cocci, prognosis is however statistically worse (at the 99% confidence limit) when prosthetic valves are present. Out of the 46 patients without prosthetic valves, 31 (68%) had a favourable bacteriological and haemodynamic evolution; in this group, gram (minus) bacilli and monilia were never found to be the pathogenic organisms. For streptococci infections, recovery was obtained in 73% of the cases (24 out of 33). Percentages of long term recovery are very similar in mitral (67%) and aortic (69%) valvular involvment, but the frequency of surgical indication was very different in either group. In cases of aortic valvular disease, valvular replacement was indicated for bacteriological or haemodynamic reasons in 19 of the 20 patients who recovered. Amongst the 9 patients who died, 6 were not operated upon. Valvular replacement is by far less frequently necessary in cases of bacterial endocarditis on the mitral valve : one prosthetic valve amongst 8 patients who recovered. Finally, the authors discuss the place of surgery in the treatment of bacterial endocarditis. According to their experience, recent improvement in the prognosis of the disease seems to depend more on the surgical approach of the problem than on the discovery of new antibiotics

Acquired activated protein C resistance in pregnancy.

Pregnancy induces several haemostatic perturbations. Some authors described possible acquired activated protein C resistance (APCR) during normal pregnancy. We wanted to test this possibility and to evaluate if this acquired APCR might contribute to the known increased tendency to thrombosis associated with pregnancy. To answer the first hypothesis, we tested APCR with standard and with modified (5) APTT assays; to explore the second one, we chose to test some hypercoagulability and hyperfibrinolysis markers, i.e. fibrinopeptide A (FPA), Fragment 1+2 (F1+2) and D-dimers, and to correlate them with APC-ratio

Treatment of the Raynaud's phenomenon with piracetam.

Piracetam (Nootropil, CAS 7491-74-9) has been investigated in the treatment of primary and secondary Raynaud's phenomenon in three sequential and complementary studies. The first study in 20 patients with primary Raynaud's phenomenon, utilising clinical and ultrasound examination, capillaroscopy and laboratory tests established a daily dose of 8 g as most effective. The second study in 58 patients (47 primary, 11 secondary) confirmed the therapeutic efficacy of piracetam in both primary and secondary Raynaud's phenomenon. The third study, of crossover design, in 30 patients with severe Raynaud's syndrome, examined various agents given singly or in combination. The results not only confirmed the efficacy of piracetam but in addition allowed comparison of the efficacy of the principal therapeutic agents or regimens used in the treatment of Raynaud's syndrome and the formulation of a list of these therapies in decreasing order of efficacy, thus: piracetam 4 g/d + buflomedil 600 mg/d; piracetam 8 g/d; buflomedil 600 mg/d; piracetam 4 g/d + acetylsalicylic acid 100 mg/d; pentoxifylline 1200 mg/d; calcium antagonists; ketanserin 120 mg/d. The particular efficacy of 8 g piracetam daily in 3 divided doses at 8-hourly intervals can be attributed to its unique dual mode of action; inhibition of platelet function by inhibition of thromboxane A2 synthetase or antagonism of thromboxane A2 and increased formation of prostaglandin I2, together with a rheological effect involving reduction in blood and plasma viscosity through an increase in cell membrane deformability and a reduction of 30-40% in the plasma concentrations of fibrinogen and von Willebrand's factor. In addition, the administration of piracetam appears to be devoided of adverse effects

Platelet anti-aggregant and rheological properties of piracetam. A pharmacodynamic study in normal subjects.

The random administration of four different single oral doses of piracetam (Nootropil, CAS 7491-74-9)--1.6 g, 3.2 g, 4.8 g and 9.6 g--at fixed intervals of 2 weeks to 5 healthy subjects has confirmed and explicited its platelet anti-aggregant and rheological properties after doses of 4.8 g and 9.6 g. The effect on platelet aggregation occurs through inhibition of thromboxane synthetase or anti-thromboxane A2 activity together with a reduction in the plasma level of von Willebrand's factor (F.VIIIR:vW). The rheological effect is related to the action of piracetam on cell membrane deformability (red cells, white cells and platelets) and to its simultaneous effect in reducing by 30-40% plasma levels of fibrinogen and von Willebrand's factor. In addition, it exerts a direct stimulant effect on prostacyclin synthesis in healthy endothelium. These effects are greatest between 1 and 4 h after dosage, and then diminish progressively to disappear between 8 and 12 h after administration. This explains the need to divide the total daily dose into 3 intakes at 8-hourly intervals. This study confirms the presence of four sites of action of piracetam: the vessel wall, platelets, plasma and cell membranes (RBC, WBC), which provide the basis for the potentially important antithrombotic activity of piracetam

Pharmacokinetics, thrombolytic efficacy and hemorrhagic risk of different streptokinase regimens in heparin-treated acute myocardial infarction.

The systemic activator activity of 4 streptokinase (SK) regimens (250,000 IU intracoronary, group A; 500,000 IU, group B; 1.5 X 10(6) IU, group C; and 30 U anisoylated plasminogen streptokinase activator complex (APSAC) intravenously, group D) was tested with the fibrin plate technique. One hour after initiation of treatment, the activator activity was highest after APSAC (3.6 +/- 0.9 U), slightly but not significantly less after SK 1.5 X 10(6) IU (3.0 +/- 0.7), and significantly less after SK 500,000 IU (1.6 +/- 0.5) and 250,000 IU (0.6 +/- 0.5), p less than 0.001. After SK, activator activity half-lives were 184 minutes (group B) and 169 minutes (group C), and after APSAC 188 minutes (group D). These were all in agreement with greater than 12 hour duration of changes in other markers of systemic fibrinolysis (euglobulin lysis time) and substrates depletion (fibrinogen, plasminogen, alpha 2 antiplasmin). In extended pilot clinical groups given identical thrombolytic regimens during full anticoagulation with heparin, angiographic coronary patency was found in 83% (35 of 42) after intracoronary SK (group 1), in 73 and 75%, respectively, after 500,000 IU (31 of 43) and 1.5 X 10(6) IU (30 of 40) (group 2 and 3, difference not significant) and 80% (8 of 10) after the 30-U bolus of APSAC (group 4). The overall hemorrhagic risk was 24%, equally distributed among the 4 regimens and mostly (91%) related to catheters. The incidence of bleeding unrelated to vessel puncture was 4%; no deaths occurred. It is concluded that APSAC is the most fibrinolytic regimen but its potential thrombolytic superiority over SK remains to be demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS

Liver transplantation and haemophilia A.

Liver transplantation has become the standard treatment for a variety of inherited metabolic disorders. We report on two patients who underwent successful transplantation for posthepatitis viral cirrhosis, which developed following blood factor replacement for haemophilia A. The second patient was transplanted before the occurrence of major complications of either his liver or haemophilic disease. We propose early liver transplantation to achieve metabolic cure of haemophilia

Hemostasis in children undergoing liver transplantation.

We reviewed the records of 200 children who underwent 238 orthotopic liver transplantations in order to determine which preoperative factors could predict intraoperative blood loss. A coagulation abnormality score (CAS) was calculated by allowing one point for each abnormality in six preoperative coagulation tests. The mean CAS values were significantly greater in children suffering from fulminant hepatic failure (Fulm) or post-necrotic cirrhosis (PNC) and those having retransplantation (ReTx) than in those with disease of other etiologies. No correlation was found between the CAS and the mean blood requirements in the different etiology groups. According to the amount of blood transfused, children could be divided in two groups. Group 1 were those with biliary atresia and ReTx, who received more than 200 ml/kg. Group 2 included those with PNC, Fulm, metabolic diseases, and Alagille syndrome and Byler disease, who received less than 140 ml/kg. The mean CAS was significantly lower and the PT significantly better in Group 1. We conclude that preoperative coagulation tests were weak predictors of intraoperative bleeding. The etiology of the underlying liver disease and previous abdominal surgery play an important role in the occurrence of severe bleeding. Intraoperatively, children presented the same hemostatic changes as adults

Atrial natriuretic factor, arachidonic acid metabolites and acute renal ischemia: experimental protocol in the rat.

The effects of an atrial natriuretic factor (ANF) infusion upon the production of the arachidonic acid metabolites (thromboxane B2, TxB2; 6-keto-prostaglandin F1 alpha, 6-keto-PGF1 alpha, PGI2, or prostaglandins E2, PGE2) were investigated after acute renal ischemia in the rat. This experimental protocol included a right nephrectomy and a 45-min left renal artery occlusion. Fifteen minutes after declamping, blood samples were collected from the left renal venous effluent for the assay of plasmatic prostanoid concentrations. Three experimental groups were studied: group I (n = 9) sham, no ischemia-group II (n = 9) control group, 45 min of left renal ischemia, followed by a 15-min revascularization, and group III (n = 10) ANF group, a similar ischemic protocol to that in group II was used but, after declamping, synthetic Atriopeptin III was infused (0.5 micrograms/kg/min) during the 15-min of vascular reflow. Fifteen minutes after declamping, TxB2 secretion significantly increased after ischemia in the control and ANF groups: TxB2: 210 +/- 22.4 pg/ml (control group) and 234.8 +/- 25.1 pg/ml (ANF group) versus 135.8 +/- 17.8 pg/ml (sham group) (p less than 0.05 and 0.01, respectively). On the other hand, the 6-keto-PGF1 alpha plasma levels were significantly higher after ischemia in the ANF group (221 +/- 34 pg/ml) in comparison with the sham (124 +/- 24.1 pg/ml) or with the control group (116.7 +/- 12.5 pg/ml). The calculated TxB2/6-keto-PGF1 alpha ratio was therefore higher in the control group, 1.93 +/- 0.27, than in physiological conditions (sham group), 1.2 +/- 0.17.(ABSTRACT TRUNCATED AT 250 WORDS

Viability of long-term cryopreserved human saphenous veins.

The feasibility of maintaining long-term viability of human venous allografts by cryopreservation has been investigated. Segments of vein were obtained from 85 patients undergoing a stripping operation for varicose veins. The venous segments were immersed in a dimethylsulfoxide 15% solution, deep frozen at -196 degrees C in liquid nitrogen and preserved for a duration of 1 week to 24 months. Light microscopy (n = 126) failed to demonstrate striking differences between control veins and any of the cryopreserved veins. The types of damage observed at scanning electron microscopy included endothelial cell separation, endothelial cell loss, exposed basement membrane and exposed fibrillar collagen, which were graded on a scale. The score for short term (less than 3 weeks) stored veins was 8.1 +/- 0.9 (mean +/- SEM) and did not differ from the long-term (greater than 10 weeks) stored veins score (6.3 +/- 1.0, p NS). The tissue enzymes LDH, GOT, GPT, CPK were measured in the frozen vein groups (n = 115) after thawing to room temperature. Cryopreservation did not alter any of the tissue enzymes measured when compared to controls. Endothelial fibrinolytic activity (FA) of 58 venous segments cryopreserved for a mean duration of 20 months was 6136.4 +/- 292.1 Tissue Activator Units (TAU) and did not differ from FA of 11 controls (5989.1 +/- 696.8 TAU). Synthesis of 6-Keto-PGF1-alpha-2, a stable breakdown product of PGI2, measured in 10 venous segments cryopreserved for 10 months, was significantly higher than in 13 veins stored in saline for 12 hours at 4 degrees C (2.8 +/- 0.4 vs 0.4 +/- 0.1 PG ml-1mg-1min-1, respectively; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS