[Proposal of guidelines for antibiotic prophylaxis in plastic, reconstructive, and aesthetic surgery]. / Proposition de recommandations sur l'antibioprophylaxie en chirurgie plastique, reconstructrice et esthétique.

BACKGROUND: In plastic surgery, guidelines about antibiotic prophylaxis are inaccurate and incomplete, due to result the absence of high-level studies on this subject. The main aim is to establish national common recommendations for plastic surgery antibiotic prophylaxis. MATERIALS AND METHODS: A working group will discuss and validate a multi-center analysis of practices in three University Hospital Centers compared to an interdisciplinary analysis of recommendations to the French Society of Anaesthesia and Intensive Care Medicine and scientific literature. This working group is composed of plastic surgeon members of the French Society of Aesthetic Reconstructive Plastic Surgery, infectious disease physicians, and anaesthesiologists to define clear and precise antibiotic prophylaxis recommendations. RESULTS: Antibiotic prophylaxis with cefazoline (or clindamycine±gentamicine in case of allergy), has been recommended for general surgery with flap or implants, for breast surgery, lipofilling, and rhinoplasty. In other plastic surgery, no antibiotic prophylaxis has been recommended. CONCLUSION: We established common recommendations for plastic surgery antibiotic prophylaxis that is the first step to update these recommendations. Now, they can be evaluated in clinical situation to validate them.

Adaptation of Amoeba Plate Test To Recover Legionella Strains from Clinical Samples.

The isolation of Legionella from respiratory samples is the gold standard for diagnosis of Legionnaires' disease (LD) and enables epidemiological studies and outbreak investigations. The purpose of this work was to adapt and to evaluate the performance of an amoebic coculture procedure (the amoeba plate test [APT]) for the recovery of Legionella strains from respiratory samples, in comparison with axenic culture and liquid-based amoebic coculture (LAC). Axenic culture, LAC, and APT were prospectively performed with 133 respiratory samples from patients with LD. The sensitivities and times to results for the three techniques were compared. Using the three techniques, Legionella strains were isolated in 46.6% (n = 62) of the 133 respiratory samples. The sensitivity of axenic culture was 42.9% (n = 57), that of LAC was 30.1% (n = 40), and that of APT was 36.1% (n = 48). Seven samples were positive by axenic culture only; for those samples, there were <10 colonies in total. Five samples, all sputum samples, were positive by an amoebic procedure only (5/5 samples by APT and 2/5 samples by LAC); all had overgrowth by oropharyngeal flora with axenic culture. The combination of axenic culture with APT yielded a maximal isolation rate (i.e., 46.6%). Overall, the APT significantly reduced the median time for Legionella identification to 4 days, compared with 7 days for LAC (P < 0.0001). The results of this study support the substitution of LAC by APT, which could be implemented as a second-line technique for culture-negative samples and samples with microbial overgrowth, especially sputum samples. The findings provide a logical basis for further studies in both clinical and environmental settings.

[Premature rupture of membranes at term on unfavourable cervix: immediate or delayed induction?]. / Rupture prématurée des membranes à terme sur col défavorable: quel délai pour déclencher ?

OBJECTIVES: To define the optimal delay before inducing labor in the management of premature rupture of the membranes (PRM) at term with unfavourable cervix in order to reduce the risk of caesarean section as well as the risk of maternal and foetal infection. MATERIALS AND METHODS: Retrospective study of three homogeneous groups carried out over on a period of 4years in two centres. All the patients were included after premature rupture of membranes at term with unfavourable cervix (Bishop score<6). We defined three expected delays after PRM at term: less than 7h (group 1), between 7 and 12h (group 2) and more than 12h (group 3). We have assessed the obstetrical, maternal and foetal consequences for each group. RESULTS: Sixty patients were allocated in group 1, 49 in group 2 and 46 in group 3. There was no significant difference in the rate of caesarean between the three groups but it was lower in group 2: 6.1% versus 18.3% in group 1 and 21.7% in group 3. No statistical difference was observed concerning maternal or foetal infections. CONCLUSION: In PRM at term, neither our study nor literature data allow us to conclude about the optimal delay before inducing labor.

The paradoxical association between inherited factor VII deficiency and venous thrombosis.

Inherited factor VII (FVII) deficiency is considered to be a haemorrhagic disease. Nonetheless, some patients paradoxically present with venous thrombosis. We assessed whether there was a link between phenotype and genotype in seven patients with inherited FVII deficiency and thrombosis (eleven venous thrombotic events). For each patient (FVII:C < 50%), clinical data were collected, aetiological assessment of risk factors for thrombosis was investigated, and direct sequencing of the nine exons and promoter of the FVII gene (F7) was performed. We present the second series ever published on FVII patients with thrombosis. In nine of the eleven thrombotic events, there was at least one classical triggering risk factor; clinical (n = 4), familial antecedent (n = 2), or biological, defined by phospholipid-binding antibodies or elevated FVIII:C levels (n = 7). In contrast to a previous series, only two events occurred after surgery, performed both with and without replacement therapy. The thrombotic event remained unexplained in one young patient, highlighting the lack of 'protection' against venous thrombosis by low FVII:C levels. Genetic mutations were found to be heterogeneous. Among the seven F7 sequence alterations identified in the present study, only two (p.Ala354Val and p.Arg364Gln) have previously been reported in FVII-deficient patients presenting with venous thrombosis. Our genetic analyses of the F7 mutations in these patients show the complexity of FVII deficiency associated with thrombosis. These data justify a holistic, clinical and biological approach for patients with these specific symptoms. This series also strongly suggest that mild FVII deficiency should not prevent physicians from using antithrombotic prophylaxis in FVII-deficient patients.

[Factor XIII deficiency in a newborn]. / Déficit en facteur XIII chez un nouveau-né.

Factor XIII deficiency is an uncommon inherited disorder which is characterized by umbilical cord bleeding and an unusually high incidence of intracranial hemorrhage. We report here a case of Factor XIII deficiency in a child that presented a caput. succedaneum as the first manifestation of the disease and then an umbilical cord bleeding. The importance of performing a quantitative FXIII assay in the presence of strong clinical suspicion is strengthened because of the normality of the standard screening tests and the important therapeutic consequences.

Impact of choice of treatment for bleeding episodes on inhibitor outcome in patients with mild/moderate hemophilia a and inhibitors.

Patients with mild/moderate hemophilia A (MHA) may develop inhibitors to factor VIII (FVIII). In this condition, FVIII clotting activity (FVIII:C) baseline levels may remain stable for some patients, but may be reduced to less than 0.01 U/mL for others. Several risk factors for the development of inhibitors in MHA have been proposed. Genetic factors, such as mutations in the FVIII gene, may play a central role; however, other influences, such as intensive treatment with FVIII products, may also be important. Optimal treatment regimens have yet to be determined, not only for the eradication of inhibitors, but also for the management or surgical prophylaxis of hemorrhages associated with this condition. Several treatment options for the control of bleeding in patients with MHA and inhibitors (MHAI) are currently available, and the choice of therapeutic strategy should be given careful consideration; some treatments may produce an anamnestic response, thus delaying the return to FVIII:C baseline levels and adversely affecting the duration of the severe bleeding phenotype. To increase our knowledge of MHAI, a retrospective collection of data is currently being performed among hemophilia centers in France and Belgium. Based on five examples of patients with MHAI collated from preliminary study data, we illustrate the impact on inhibitor outcome of the therapeutic choices used to treat bleeding episodes in these patients.

Continuous infusion of B-domain deleted recombinant factor VIII (ReFacto) in patients with haemophilia A undergoing surgery: clinical experience.

This retrospective, open-label, non-comparative study evaluated continuous infusion of recombinant factor VIII (ReFacto), B-domain deleted recombinant FVIII (BDDrFVIII), in patients with haemophilia A undergoing surgery and requiring >5 consecutive days of treatment. Sixteen patients from eight centres underwent a total of 20 procedures. Haemostatic outcome was assessed as 'excellent' or 'good' in 75% of procedures, and target FVIII:C levels were maintained throughout the continuous infusion period. The reported volume of blood loss during surgery was also within the normal range for non-haemophilic patients for the type of surgery performed. Red blood cell transfusions were required to balance excessive blood loss during BDDrFVIII continuous infusion in eight (40%) procedures (seven patients), five with bleeding or requiring volume replacement and three to treat anaemia secondary to blood loss. Non-serious adverse events considered by investigators as possibly or probably related to BDDrFVIII continuous infusion were infrequent (n = 5) considering the duration of treatment (n =239 cumulative days of continuous infusion), and all of these were mild-to-moderate in severity. No thromboembolic complications were reported except for one case of thrombophlebitis occurring at the infusion site. Only two patients (four events) experienced serious adverse bleeding; BDDrFVIII was otherwise well-tolerated. These data show that continuous infusion of BDDrFVIII provides reliable haemostasis and is an effective and well-tolerated regimen for patients with haemophilia A undergoing surgery.

[Past, present and...future of breast implants]. / Passé, présent et...avenir des prothèses mammaires.

The past of breast implants is well known, the techniques seem to be up to date and the future definitely optimistic. Breast implants have been at the top of the polemic due to their complications. Technical innovations allow plastic surgeons to choose adequate types of breast implants and also improve the innocuity of this surgery. Due to the last juridic reglementation and behaviour's evolution, breast augmentation will probably keep its place at the top.

Poor anticoagulant response to tissue factor pathway inhibitor in patients with venous thrombosis.

Tissue factor pathway inhibitor (TFPI) is of major importance in regulating the coagulation triggering effects of tissue factor. An association between TFPI deficiency and thrombosis has still not been clearly demonstrated. We evaluated the anticoagulant activity of exogenous TFPI added either to the plasma of patients with venous thrombosis (n = 118) or to the plasma of healthy controls similar in terms of mean age and sex ratio (n = 107). A poor anticoagulant response to TFPI, defined as TFPI resistance, was observed in 4.7% of controls and in 11.0% of patients. TFPI resistance was associated with an almost threefold increase in the risk of thrombosis and could therefore represent a novel hemostatic risk factor for venous thrombosis.

Three new flavonol malonylrhamnosides from Ribes alpinum.

Three new flavonol malonylrhamnosides, 3-O-(4"-O-malonyl)-alpha-L-rhamnopyranosides of mearnsetin, myricetin and quercetin respectively, together with the corresponding mearnsitrin, myricitrin, quercitrin and the 4-O-methyl phloracetophenone 2-O-beta-D-glucopyranoside, were isolated from the leaves of Ribes alpinum and fully characterized by spectrocopic methods including 2D NMR.

Molecular analysis of the genotype-phenotype relationship in factor VII deficiency.

Factor VII (FVII) deficiency is a rare haemorrhagic condition, normally inherited as an autosomal recessive trait, in which clinical presentation is highly variable and correlates poorly with laboratory phenotype. The FVII (F7) gene was sequenced in 48 unrelated individuals with FVII deficiency, yielding a total of 23 novel lesions including 15 missense mutations, 2 micro-deletions, 5 splice junction mutations and a single base-pair substitution in the 5' untranslated region. Family studies were performed in order to distinguish the contributions of individual mutant F7 alleles to the clinical and laboratory phenotypes. Specific missense mutations were evaluated by molecular modelling in the context of the FVIIa-tissue factor crystal structure. Single base-pair substitutions in splice sites and the 5' untranslated region were studied by in vitro splicing assay and luciferase reporter gene assay, respectively. All probands were also typed for four previously reported F7 polymorphisms. In the majority of cases of FVII deficiency studied here, consideration of both mutational and polymorphism data permitted the derivation of plausible explanations for the FVII activity and antigen levels measured in the laboratory. Inter-familial variation in FVII activity and the antigen levels of heterozygous relatives of probands was found to be significantly higher than intra-familial variation, consistent with the view that the nature of the F7 gene lesion(s) segregating in a given family is a prime determinant of laboratory phenotype. Although no relationship could be discerned between laboratory phenotype and polymorphism genotype, the frequencies of the A2 and M2 polymorphic alleles were significantly higher in the FVII-deficient individuals tested than in controls. This suggests that the presence of these alleles may have served to increase the likelihood of pathological F7 gene lesions coming to clinical attention.

Molecular analysis of the genotype-phenotype relationship in factor X deficiency.

Factor X deficiency is a rare haemorrhagic condition, normally inherited as an autosomal recessive trait, in which a variable clinical presentation correlates poorly with laboratory phenotype. The factor X (F10) genes of 14 unrelated individuals with factor X deficiency (12 familial and two sporadic cases) were sequenced yielding a total of 13 novel mutations. Family studies were performed in order to distinguish the contributions of individual mutant F10 alleles to the clinical and laboratory phenotypes. Missense mutations were studied by means of molecular modelling, whereas single basepair substitutions in splice sites and the 5' flanking region were examined by in vitro splicing assay and luciferase reporter gene assay respectively. The deletion allele of a novel hexanucleotide insertion/deletion polymorphism in the F10 gene promoter region was shown by reporter gene assay, to reduce promoter activity by approximately 20%. One family manifesting an autosomal dominant pattern of inheritance possessed three clinically affected members who were heterozygous for a splice-site mutation that was predicted to lead to the production of a truncated protein product. A model which accounts for the dominant negative effect of this lesion is presented. Variation in the antigen level of heterozygous relatives of probands was found to be significantly higher between families than within families, consistent with the view that the nature of the F10 lesion(s) segregating in a given family is a prime determinant of the laboratory phenotype. By contrast, no such relationship could be discerned between laboratory phenotype and polymorphism genotype.

Efficacy and safety of danaparoid sodium (ORG 10172) in critically ill patients with heparin-associated thrombocytopenia.

OBJECTIVE: To evaluate the effectiveness and the safety of danaparoid sodium in the treatment of critically ill patients with standard unfractionated heparin-induced thrombocytopenia (HIT) or low-molecular-weight HIT. SETTING: University hospital. PATIENTS AND METHODS: Retrospective analysis of 42 consecutive critically ill patients who were admitted for HIT between October 1992 and February 1997 and were treated either with therapeutic or prophylactic doses of danaparoid sodium. RESULTS: Among the 26 patients treated with therapeutic doses, neither new thrombotic complications nor thrombosis extension was clinically suspected. Two deaths were directly related to lower limb acute arterial thrombosis associated with HIT. Two major hemorrhagic complications were observed when aspirin in addition to danaparoid sodium was administered. When danaparoid sodium was used in prophylactic doses (20 courses of treatment) to prevent either postsurgical or medical thrombotic complications, no thrombotic event was observed. No death related to HIT or danaparoid sodium treatment was observed. One aggravation of a postsurgical cerebral lesion was observed. During danaparoid sodium treatment, a persistence or a recurrence of thrombocytopenia was observed in 6.5% of patients without thrombotic complications. CONCLUSION: Danaparoid sodium appears to be an efficient and safe treatment in critically ill patients with HIT. The concomitant use of aspirin in addition to danaparoid sodium seems to represent an important additional hemorrhagic risk that should be avoided in patient management.

Pharmacokinetic and pharmacodynamic variations of acenocoumarol orally administrated either once or twice daily in patients with deep venous thrombosis.

The literature suggests that variations in anticoagulant effect occur when acenocoumarol is administrated in a daily dose. We assessed the anticoagulant effects of acenocoumarol with INR, factors VII and X and protein C in 12 randomly selected hospitalised patients with deep-vein thrombosis, six of them receiving a daily dose of acenocoumarol, the other six receiving twice daily doses. When the drug effect had been at a steady-state for at least 72 h, five blood samples were drawn per patient over a period of 24 h. No nycthemeral significant variations were noted for INR, factor X and protein C in the two groups (P > 0.10). Nycthemeral significant variation in factor VII when acenocoumarol was administered once daily was noted (P = 0.02), but the clinical relevance of factor VII variation at steady-state is uncertain. In spite of the short pharmacokinetic half-life of acenocoumarol, a stable nycthemeral pharmacodynamic activity was observed after once daily administration; twice-daily administration of acenocoumarol does not appear to be justified.

Structural investigations of basic amphipathic model peptides in the presence of lipid vesicles studied by circular dichroism, fluorescence, monolayer and modeling.

A cationic amphiphilic peptide made of 10 leucine and 10 lysine residues, and four of its fluorescent derivatives in which leucines were substituted by Trp residues at different locations on the primary sequence have been synthesized. The interactions of these five peptides with neutral anionic or cationic vesicles were investigated using circular dichroism, steady state and time-resolved fluorescence with a combination of Trp quenching by brominated lipid probes, monolayers, modeling with minimization and simulated annealing procedures. We show that all the five peptides interact with neutral and anionic DMPC, DMPG, DOPC or egg yolk PC vesicles. The binding takes place whatever the peptide conformation in solution is. In the case of DMPC bilayers the binding free energy DeltaG is estimated at -8 kcal mole-1 and the number of phospholipid molecules involved is about 20-25 per peptide molecule. Peptides are bound as single-stranded alpha helices orientated parallel to the bilayer surface. In the anchoring of phospholipid head groups around the peptides, the lipid molecules are not smeared out in a plane parallel to the membrane surface but are organized around the hydrophilic face of the alpha helices like 'wheat grains around an ear' and protrude outside the bilayer towards the solvent. We suggest that such a lipid arrangement generates transient structural defects responsible for the membrane permeability enhancement. When an electrical potential is applied, the axis of the peptide helices remains parallel to the membrane surface and does not reorient to give rise to a bundle of helix monomers that forms transmembrane channels via a 'barrel stave' mechanism. The penetration depth of alpha helices in relation to the position of phosphorus atoms in the unperturbed lipid leaflet is estimated at 3.2 A.

Two distinct truncated variants of ankyrin associated with hereditary spherocytosis.

We present two distinct truncated variants of ankyrin associated with mild to moderate hereditary spherocytosis. Ankyrin Saint-Etienne 1 was manifested by an additional band located between bands 2.1 and 2.2. It was associated with a nonsense mutation in exon 39: TGG-->TGA; W1721X. Ankyrin Saint-Etienne 2 appeared as two faint bands underlining bands 2.1 and 2.2. It was associated with a nonsense mutation in exon 41: CGA-->TGA; R1833X. Overall ankyrin was diminished in splenectomized patients. Messenger RNAs Saint-Etienne 1 and 2 amounted to 20 and 37% of the total ankyrin mRNA, respectively. Ankyrin molecules truncated in their C-terminal region retain some ability to bind to the membrane whereas the bulk of nonsense mutations, located in more upstream regions, result in the mere disappearance of one haploid set of ankyrin. In the present cases, it was not possible to apportion the roles of ankyrin reduction and truncation in the pathogenesis of hereditary spherocytosis.

Prevalence of factor V Leiden (APCR) and other inherited thrombophilias in young patients with myocardial infarction and normal coronary arteries.

OBJECTIVE: To investigate the role of activated protein C resistance (APCR, factor V Leiden) in coronary artery thrombosis. METHODS: The prevalence of APCR and of congenital deficiencies of antithrombin III, protein C, protein S, plasminogen, and factor XII was investigated in adult patients under 45 years of age with acute myocardial infarction. The results were compared with those of a group of 53 age and sex matched control subjects. RESULTS: Among 75 patients under the age of 45 years who were admitted from November 1994 to April 1996 for acute myocardial infarction, 22 (29.3%) had normal coronary arteriography (group I) and 53 (70.7%) had significant coronary artery disease (group II). Inherited thrombophilia was more often found in group I (4/22, 18.2%) than in group II (4/53, 7.5%) but the difference was not significant (F test: p = 0.22). The prevalence of APCR was 9.1% (2/22) in group I, 3.8% (2/53) in group 2 (p = 0.57), and 3.8% (2/53) in the normal control group (p = 0.57). CONCLUSIONS: The prevalence of congenital thrombophilias, including APCR, does not seem to be increased in young patients with myocardial infarction and normal coronary angiograms, compared with young patients with coronary atherosclerosis and with normal control subjects. However, the statistical power of the study is too low to detect a significant difference and these results are published to allow a meta-analysis of this problem in the future.

[Thrombopenia induced by heparin: treatment with Org 10172. Tolerability and efficacy]. / Thrombopénie induite par l'héparine: traitement par l'ORG 10172. Tolérance et efficacité.

OBJECTIVES: Heparin-induced thrombocytopenia is a relatively common and potentially serious adverse complication of heparin treatment. After heparin withdrawal initiation of an alternative anticoagulant is often indicated. Org 10172 or Orgaran is a mixture of several non-heparin low molecular weight glycosaminoglycans with proven antithrombotic efficacy. Unlike low molecular weight heparins, Org 10172 has a low cross reaction rate (about 10%) with the heparin-dependent antibody. METHODS: We present nine patients with heparin induced thrombocytopenia. Org 10172 was prescribed to treat or to prevent a thromboembolic event. RESULTS: Seven patients required further parenteral anticoagulant at diagnosis of heparin-induced thrombocytopenia. Org 10172 was given at prophylactic doses for three patients with a high thrombosis risk and at therapeutic doses for four patients who presented either a venous or an arterial thrombosis related to thrombocytopenia. Two patients presented heparin-induced thrombocytopenia four to six years earlier and needed a parenteral anticoagulation treatment in a post-operative period. CONCLUSION: For the nine patients, Org 10172 was a safe and effective antithrombotic treatment. However, strict monotoring of the platelet count is absolutely mandatory during Org 10172 therapy.

Effects of tachykinins on identified dorsal vagal neurons: an electrophysiological study in vitro.

Intracellular current-clamp recordings were performed using in vitro brainstem slice preparations to compare the actions of substance P, neurokinin A, neurokinin B and their agonists on rat dorsal vagal nucleus neurons with or without antagonists of neurokinin 1 and 2 receptors. The agonists used were either [Sar9,Met(O2)11]substance P or septide for neurokinin 1 and [Nle10]neurokinin A(4-10) for neurokinin 2 receptors. The antagonists were spantide, SR 140333 or RP 67580 for neurokinin 1 receptors and SR 48968 for neurokinin 2 receptors. Identification of vagal neurons was achieved electrophysiologically by testing antidromic responses and confirmed morphologically by an intracellular injection of biocytin. Of the 70 neurons tested, substance P led to depolarization in 36, hyperpolarization in six and no effect in 28. Depolarization was concentration dependent and generally associated with an increase of the membrane input resistance. Addition of tetrodotoxin (1 microM) to the medium had no effect on depolarization. RP 67580 (1 microM) blocked depolarization, but spantide and SR 140333 (microM to 50 microM) did not. Hyperpolarization was never observed using agonists. Neurokinin A and neurokinin 2 agonist induced concentration-dependent depolarization associated with an increase in membrane input resistance in eight of 14 neurons and in four of nine neurons, respectively. Depolarization was only partially abolished by the neurokinin 2 antagonist SR 48968. Neurokinin B had no effect in any of the eight neurons tested. These data prove that vagal neurons have neurokinin 1 and 2 receptors and that tachykinin could produce either depolarization or hyperpolarization. Since membrane potential variations were associated with an increase (during depolarization) or decrease (during hyperpolarization) in the membrane input resistance and since the reversal potential was close to the potassium equilibrium potential, we speculate that these effects are mediated by modulation of potassium conductance.