Role of both actin-myosin cross bridges and NO-cGMP pathway modulators in the contraction and relaxation of human placental stem villi.

INTRODUCTION: Human placental stem villi (PSV) present contractile properties. We studied the role of actin-myosin cross bridges (CBs) and the effects of NO-cGMP pathway modulators in the PSV contraction and relaxation. METHODS: In vitro contractile properties were investigated in 71 PSV from term human placentas studied according to their long axis. Contraction was induced by both KCl and electrical tetanic stimulation. Relaxation was induced by inhibiting the CB cycle with either 2,3-butanedione monoxime (BDM) or blebbistatin (BLE) and by activating the NO-cGMP pathway with isosorbide dinitrate (ISDN), sildenafil (SIL) or ISDN + SIL. RESULTS: PSV tension slowly increased by 140% of the basal tone after KCl exposure and by 85% after tetanus. The addition of BDM, BLE, ISDN, SIL and ISDN + SIL induced a relaxation of PSV, the overall time course of relaxation (in s) was respectively (means ± SD) 3412 ± 1904, 14,250 ± 3095*, 3813 ± 1383, 2883 ± 1188 and 2440 ± 477; significantly longer in BLE compared with BDM, ISDN, SIL and ISDN + SIL:*p < 0.001). the overall time course of relaxation (in s) was respectively (means ± SD) 3412 ± 1904, 14,250 ± 3095*, 3813 ± 1383, 2883 ± 1188 and 2440 ± 477; significantly longer in BLE compared with BDM, ISDN, SIL and ISDN + SIL:*p < 0.001). These relaxation kinetics were particularly slow. Other relaxation parametres, i.e., maximum lengthening, -peak dT/dt, and resting tension, did not differ between these 5 subgroups. DISCUSSION AND CONCLUSION: Isolated human PSV were able to contract after both KCl exposure and tetanus. This increase in contractility was reversed by inhibiting the CB cycle with BDM or BLE and by stimulating the NO-cGMP pathway with ISDN or SIL. The association ISDN + SIL did not potentiate the relaxing processes.

[Performances of an automated dispensing system combined with a computerized prescription order entry]. / Performances d'une solution associant l'automate de délivrance Pillpick au logiciel de prescription Pharma utilisée pour une activité de dispensation à délivrance nominative dans une unité de consultation et de soins ambulatoire.

INTRODUCTION: Performances of an automated dispensing system Pillpick (Swisslog) coupled with the computerized-prescribing - order-entry software and dispensing software Pharma (Computer Engineering) implemented at the opening of a new prison facility in Meaux were quantitatively and qualitatively evaluated. Pillpick allows the treatment of different and varied pharmaceutical forms without imposing bulk handling or depackaging. METHOD: This study conducted between July and September 2006 focused on the performances of the automated dispensing system in terms of single dose packaging, single dose dispensing, dispensing error rate and security of the medication circuit. RESULTS: Seventy-six plus or minus five percent of the prescribed medications were automated dispensed. Packaging working flow rate was 377 units doses per hour, dispensing working flow rate was 537 doses per hour. Dispensing error rate was 0.5%, due to wrong delivery orders mainly generated by the Pharma computer-order entry software. DISCUSSION: Automated dispensing systems Pillpick ensure safe drug dispensing. Potential drug errors can possibly be generated by the computerized-prescribing - order-entry software and dispensing software. CONCLUSION: The robot-software combination constitutes the key performance parameter.

[Development of surgical antibioprophylaxis kits: evaluation of the impact on prescribing habits]. / Création de kits d'antibioprophylaxie chirurgicale: évaluation de l'impact sur les habitudes de prescription.

In our hospital, surgical antibioprophylaxis (ATBP) was too often administered too late, thus raising the infectious risk. Antibiotic stocks of the anaesthesia department were also systematically used, instead of nominal prescriptions of these drugs. The pharmacy could neither charge antibiotics to each surgical department nor quantify and differentiate ATBP from curative antibiotic therapy. The pharmacy and anaesthesia departments therefore set out to standardize surgical ATBP, in order to adapt this treatment to each surgical indication, and particularly in the case of allergy to beta-lactamase antibiotics (second line treatment kits). Consequently, prescription forms were developed and supplied to each surgery department, as well as ATBP kits. The kits were prepared and distributed by the pharmacy, and comprised boxes containing antibiotics in sufficient quantities to respect the protocols approved by the French Society of Anaesthesia and Resuscitation (SFAR). A protocol describing prescriptions, dispensation and administration has been presented to physicians and nurses. Fifteen surgical departments were included in our study and 30 different kits were prepared. From 1998 to 2001, 5586 surgical operations required administration of a kit (second line treatment kits in 5% of cases): 1848 (33%) in visceral surgery; 764 (13.8%) in urology; 802 (14%) in orthopaedics; 13 (0.2%) in vascular and thoracic surgery; 1236 (22%) in ear-nose-throat (ENT), periodontics and ophtalmology, and 923 (17%) in gynaecology and obstetrics. 93% of filled prescriptions forms were spontaneously returned to the pharmacy, the others were obtained during the renewal of kit stocks. The cost (over 4 years) of ATBP was quantified: 157,871 F for the 15 departments included, 26,123 F in visceral surgery, 13,520 F in urology, 73,741 F in orthopaedics, 569 F in vascular surgery, 39,720 F in ENT/ophthalmology/periodontics and 4,198 F in gynaecology and obstetrics. According to the Altemeier classification, 2226 class I, 3151 class II, and 209 class III surgical operations were performed. Since the kits have been brought into use, the committee for the protection against nosocomial infections (CLIN) has observed a reduction in the incidence of post-operative infections, according to the Altemeier classification: from 1.6% to 0.5% in class I, from 6.5% to 4.3% in class II, and from 11% to 8.5% in class III. The difference was statistically significant only for classes I (p < 0.01) and II (p < 0.001), and unchanged for class III (p = 0.3). No analysis was carried out for class IV (curative treatments). Both nurses and physicians have greatly appreciated the implementation of this organization. The advantage in terms of post-operative infections, administration exhaustiveness and stock management is obvious. The prescribed kits were systematically appropriate for the surgical interventions. In orthopaedics, cefamandole was used over 24 h (188 kits) in ligament plasty and osteotomy, or for 48 h (499 kits) in prosthetic surgery; 24 amoxicillin/clavulanic acid (first line) and 9 clindamycin/gentamicin (second line) single dose kits have been prescribed in traumatic indications. In ophthalmology, kits were only prescribed in endophtalmitis (24 ofloxacin/fosfomycin single amount kits), implant replacement or cornea graft (1076 ofloxacin 24 h kits) and cataract surgery in diabetic patients (12 ofloxacin single amount kits). In ENT and periodontics, 124 surgical operations required cefazolin single dose kits. In vascular surgery, 5 pefloxacin/gentamicin 48 h kits and 1 amoxicillin/clavulanic acid 48 h kit were used in contaminated limb amputation, 1 cefamandole 48 h kit in class I surgery and 1 vancomycin 24 h kit (betalactamase antibiotic allergy); in thoracic surgery, 1 cefamandole 24 h kit was used for a thoracic wound. In visceral surgery, 9 different kits have been used, depending on the opening (class II) or not (class I) of the digestive tract. 797 cefazolin (first line) and 68 clindamycin/gentamicin (second line) single dose kits were used in class I surgery, and 689 amoxicillin/clavulanic acid single dose (SD) kits in class II surgery. Specific protocols consisted of 18 ceftriaxone/metronidazole and 48 metronidazole/gentamicin SD kits in oesophagus surgery, 11 ceftriaxone and 17 gentamicin SD kits in biliary endoscopy, 137 metronidazole SD kits in proctology and 34 amoxicillin/gentamicin 6 h kits for prevention of endocarditis. In urology, 133 cefotaxime and 20 pefloxacin/gentamicin SD kits were precribed in renal lithiasis, 102 amoxicillin/clavulanic acid SD kits in cystectomy, 27 amoxicillin/gentamicin 6 h kits in endocarditis prevention and 58 cefamandole SD kits in all other indications. In gynaecology and obstetrics, 534 cefazoline and 19 clindamycin/gentamicin (second line) SD kits were used, and 370 doxycyclin SD kits were prescribed in pregnancy termination. Some departments (orthopaedics and visceral surgery) adapted the protocols to their needs, specifically with regard to treatment duration. However, these situations were quickly corrected. A constant follow-up and update of this system, associated with routine audits, should allow the maintenance and possibly the improvement of these results, hence shortening treatment duration.

[Management of heparin-induced thrombocytopenia]. / Prise en charge des thrombocytopénies induites par l'héparine.

Immune-mediated (type II) heparin-induced thrombocytopenia (HIT) is a common and potentially serious averse effect of heparin therapy. Early diagnosis is needed in order to prevent complications such as venous and arterial thromboembolic events. Clinical management of patients with type II HIT is difficult. In most cases, immediate cessation of heparin therapy is required, and continuation with alternative antithrombotic treatment is recommended. Currently, there is no consensus about the optimal anticoagulation therapy for type II HIT. A literature review regarding new antithrombotics and their role in HIT was carried out, using Medline. The pharmacologic characteristics as well as the clinical evaluation of direct inhibitors of thrombin (argatroban, inogatran, melagatran, ximelagatran, efegatran and napsagatran) and fondaparinux, a synthetic pentasaccharide were reported. There new anticoagulants are not available yet in France, so sodium danaparoid and lepirudin are the only effective antithrombotics officially induced in HIT, and constitute an important therapeutic advance. A procedure for HIT prophylaxis or thrombosis treatment with HIT was assessed. No comparative test concerning sodium danaparoid and lepirudin is available. The selection could not be based on clinical arguments, but the cost of treatment could constitute a selection criterion. The comparison of the treatment cost for a patient weighing 70 kg, and presenting with symptomatic HIT, was in favour of sodium danaparoid. Because of the increased risk of haemorrhage with lepirudin, and the less convenient administration methods for this drug, the prescription of sodium danaparoid as first-line therapy, following a test of platelet aggregation can be justified. The monitoring of a treatment by sodium danaparoid or by lepirudin could be carried out within our establishment. For all these reasons, we chose the systematic use of lepirudin in the event for symptomatic HIT thus in emergency. In patients presenting asymptomatic HIT, or with a history of HIT and for which a surgical operation requiring an active anticoagulant was programmed, sodium danaparoid must preferentially be used, only if the test of crossed reactivity with sodium danaparoid is negative. The absence of crossed reactivity of the heparin-dependent antibodies against sodium danaparoid should be systematically tested, imperatively during the acute phase of HIT. The conversion to vitamin K antagonists must be considered as soon as possible, after HIT correction. HIT should be largely prevented by limiting the duration of heparin administration and by monitoring platelet numeration, twice-weekly during the first three weeks of treatment, and in the event of its prolongation, to be carried out once a week. This approach should decrease the number of cases of thrombocytopenia due to heparin.

[Septic shock and selenium administration]. / Choc septique et administration de sélénium.

Selenium is an essential trace element. In the form of selenocysteine, an amino acid, selenium is necessary for the activity of important enzymes (i.e. glutathione peroxidases, thioredoxin reductase). In the periodic table of the elements, selenium belongs to the same column as oxygen. In fact, seleno-enzymes have an important role in the detoxification of reactive oxygen species, especially peroxides and hydroperoxides. In septic and septic-like shock patients, reactive oxygen species, particularly peroxides, play an important role through their destructive actions, which are favourable as critical components of microbial destruction and also deleterious in excessive generation. This excessive generation results in tissue damage. Moreover, reactive oxygen species modulate the activation of important intracellular mediators (NF kappa B activation, arachidonic acid cascade). Simultaneously in patients with severe infection, there is a marked and early plasma selenium decrease. Redistribution due to selective selenium uptake for metabolic use could be one of the main mechanisms for this decrease. This review was carried out by questioning on the one hand the Medline database, by consulting the reviews and works available in the services of biology, biochemistry and pharmacy, by a prospective follow-up on the subject in Current Contents, but also thanks to library searches carried out by Aguettant laboratories. Several supplementary studies at various doses (from 140 to 1000 micrograms/day sodium selenite) have been conducted, though only on small groups of patients and with a questionable design. Selenium treatment seem to be promising in severely septic patients. However, in the absence of pertinent clinical data, only the administration of doses below adverse effect levels, staying within physiological limits, can presently be recommended (i.e. 200 to 500 micrograms/day of sodium selenite).

[Preventive treatment of thrombosis: audit on heparin prescription]. / Traitement prophylactique de la thrombose: audit sur la prescription des héparines. Comité du Médicament du CHG de Meaux.

An audit has been carried out, in a French general hospital, studying the use of heparins in preventive indications, to assess concordance between prescriptions and thrombotic risk, before and one year after the diffusion of national guidelines. Platelet monitoring frequency has also been studied. On a defined day, 550 patients were admitted, and 113 treated with preventive heparinotherapy (low molecular-weight heparin: 98 per cent). 52.2 per cent of patients received a correct regimen, while 4.4 per cent of underprescriptions and 43.4 per cent of overprescriptions were observed. Platelet monitoring protocol was respected in 44 per cent of cases, while it was insufficient for 41 per cent and not carried out in 15 per cent. The results of this study have been communicated to all the prescriptors. Another audit done one year later showed that 81 per cent of doses were adapted to the thrombotic risk, 2 per cent were too low, and 17 per cent too high. The efficiency of this kind of process shows that it should be generalized to all the sensitive therapeutic classes.