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Water is a vital resource, a primary element for humans and an essential source for the survival and development of any productive sector. It is a responsibility for everyone, as well as for institutions, to defend, protect and preserve water as the essence of life and the security for future generations. Hence arises the modern setting of water management in agriculture, based on stringent criteria of efficiency and environmental protection, required also by the EU and national legislation. The threat of climate change, the effects of which have an impact on the water cycle and are particularly evident in the Mediterranean area, requires an integrated approach to water management and policies. It is therefore necessary to ensure policies based on governance models compatible with various demands of use, taking into account the trends of water consumption and availability. Water covers 70% of our planet, and it is easy to think that it will always be plentiful. However freshwater - the stuff we drink, bathe in, irrigate our farm fields with -- is incredibly rare. Only 3% of the world's water is freshwater, and two-thirds of that is tucked away in frozen glaciers or otherwise unavailable for our use.

We have developed an objective procedure, using a modified retinal camera, to determine macular pigment (MP) optical density distributions in the human retina. Using two multi-band filters, reflectance maps of the retinas of young subjects (

In order to increase the aerodynamic performances of their engines, aircraft engine manufacturers try to minimize the clearance between rotating and stationary parts in axial and centrifugal compressors. Consequently, the probability of contact increases, leading to undesirable phenomena caused by forced excitation of the natural modes, or by modal interaction. Due to the complexity of these phenomena, many numerical studies have been conducted to gain a better understanding of the physics associated with them, looking primarily at their respective influence on potential unstable behaviors. However, the influence of other physical phenomena, such as friction and wear, remains poorly understood. The aim of this work is to show some effects associated with friction and wear on the dynamic behavior resulting from blade-to-casing interaction. The numerical study reported here is based on a simplified finite element model of a rotating bladed disk and a flexible casing. The contact algorithm uses an explicit time marching scheme with the Lagrange multipliers method. Friction and wear are formulated using respectively Coulomb’s and Archard’s Laws. The rotational speed is set to critical speed giving rise to modal interaction between a backward mode of the casing and a counter-rotating mode of the bladed disk with one nodal diameter. Contact is initiated by a dynamic excitation of the stator. In the presence of friction, the system becomes unstable when a sideband of the excitation frequency coincides with a one nodal diameter mode of the bladed disk. The introduction of wear leads to a vibration reduction, while the abradable material is removed by the wear process. The number of wear lobes produced on the casing is related to the ratio between the vibration frequency of the blades and the rotating speed. The ratio obtained by means of the FE model corroborates experimental observations.

Resume Les staphylocoques ont developpe depuis longtemps une resistance a la meticilline et plus de 30 % des souches de staphylocoque dore sont maintenant resistantes a la meticilline. Plusieurs cas d’echec d’un traitement par la vancomycine ont ete recemment rapportes, correspondant a des souches de sensibilite diminuee a la vancomycine. Il convient donc pour traiter les infections severes de s’assurer d’une concentration de vancomycine a la vallee entre 15 et 20 mg/L, de telle sorte que les concentrations seriques excedent largement la CMI. L’utilisation d’autres antibiotiques actifs contre les staphylocoques est passee en revue et les avantages potentiels des nouveaux antistapylococciques sont discutes.

Polycrystalline samples of monoclinic zirconia (α-ZrO 2 ) have been irradiated at room temperature with 190 MeV 36 Ar and 170 MeV 84 Kr ions in the electronic slowing down regime. Room-temperature X-ray diffraction (XRD) and micro-Raman spectroscopy measurements show consistently that a phase transition to the tetragonal form (β-ZrO 2 ) occurs for 170 MeV 84 Kr ion irradiation above an electronic stopping power value around 15 MeV μm −1 . The kinetics of the transition were monitored by on-line XRD measurements on the same sample. No such phase transformation is seen with 190 MeV 36 Ar ion irradiation for an electronic stopping power value around 6 MeV μm −1 . The plot of the tetragonal phase fraction deduced from XRD measurements vs fluence is analysed with single-impact and double-impact kinetic models. The data seem to be in favour of a double ion impact process.

Nosocomial pneumonia is a frequent complication in hospitalized patients. Gram-positive pathogens, particularly Staphylococcus aureus, are responsible for the increasing frequency of nosocomial pneumonia. To evaluate the efficacy and safety of intravenous quinupristin/dalfopristin (Synercid) in the treatment of nosocomial pneumonia caused by gram-positive pathogens we conducted a prospective, randomized, open-label, international, multicenter, comparative clinical trial. Two hundred ninety-eight patients with nosocomial pneumonia were enrolled in 74 active centers in five countries: a subgroup of 171 (87 quinupristin/dalfopristin-treated and 84 vancomycin-treated patients) were evaluable for the major efficacy end points. One hundred fifty received 7.5 mg/kg of quinupristin/dalfopristin every 8 h; 148 patients received 1 g of vancomycin every 12 h. Aztreonam at a dose of 2 g every 8 h could be administered in both groups for coverage of gram-negative organisms, and tobramycin was added for coverage against Pseudomonas aeruginosa. The primary efficacy end point was the clinical response between the seventh and the thirteenth day after the end of treatment in clinically evaluable patients with documented causative pathogen(s) at baseline (bacteriologically evaluable population). Therapy was clinically successful (cure or improvement) in 49 (56.3%) of patients receiving quinupristin/dalfopristin and 49 (58.3%) patients receiving vancomycin (difference, -2.0% [95% CI, -16.8% to 12.8%]) in the bacteriologically evaluable population. Equivalent clinical success rates were also observed in the all-treated population (n = 298), and in the bacteriologically evaluable patients intubated in baseline (39/72 [54%] compared with 36/67 [54%]). The by-pathogen bacteriologic response was similar in both treatment groups, with equivalent clinical success rates for Streptococcus pneumoniae, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus. Adverse events (venous and nonvenous) were equally distributed between groups; 15.3% of quinupristin/dalfopristin patients and 9.5% of vancomycin patients discontinued therapy because of an adverse clinical event. In this study quinupristin/dalfopristin was shown to be equivalent to vancomycin in the treatment of nosocomial pneumonia caused by gram-positive pathogens. Quinupristin/dalfopristin merits further evaluation for the treatment of nosocomial pneumonia caused by methicillin-resistant S. aureus.

Summary Objective To determine whether a new protocol for ordering liver function tests could decrease their number, and consequently the costs. Design This prospective study was conducted between October and November 1996, with October–November 1995 as the baseline period. According to the new guidelines, at admission to the ICU total and conjugated bilirubin, aspartate alanine transferase, and aspartate amino transferase were ordered as usual; alkaline phosphatase and gamma glutamyl transpeptidase were ordered only in particular situations. Subsequently, aspartate amino transferase and conjugated bilirubin were not ordered systematically. Setting A17 bed medical ICU in a tertiary university hospital. Patients All patients admitted to the ICU during both periods. Main outcome measurements Impact of the new guidelines on the number of the liver function tests ordered in 1996. Results 1) The clinical characteristics of both populations were similar. 2) The number of each liver function test ordered per patient per day was lower in 1996 vs. 1995 (P Conclusion Application of these new guidelines might substantially lower the number of liver function tests ordered and thus their cost ($4075). No change was observed for length of stay or survival.

Light exposure has been implicated in age-related macular degeneration (AMD). This study was designed to measure cumulative light distribution on the retina to determine whether it peaked in the macula. An eye-tracker recorded the subject's field of view and pupil size, and superimposed the gaze position. Fifteen naïve subjects formed a test group; 5 formed a control group. In phase 1, all subjects viewed a sequence of photographic images. In phase 2, the naïve subjects observed a video; in phase 3, they performed computer tasks; in phase 4, the subjects walked around freely. In phase 1, control subjects were instructed to gaze at bright features in the field of view and, in a second test, at dark features. Test group subjects were allowed to gaze freely for all phases. Using the subject's gaze coordinates, we calculated the cumulative light distribution on the retina. As expected for control subjects, cumulative retinal light distributions peaked and dipped in the fovea when they gazed at bright or dark features respectively in the field of view. The light distribution maps obtained from the test group showed a consistent tendency to peak in the macula in phase 3, a variable tendency in phase 4, but little tendency in phases 1 and 2. We conclude that a tendency for light to peak in the macula is a characteristic of some individuals and of certain tasks. In these situations, risk of AMD could be increased but, at the same time, mitigated by the presence of macular carotenoids.

Light exposure has been implicated in age-related macular degeneration (AMD). This study was designed to measure cumulative light distribution on the retina to determine whether it peaked in the macula. An eye-tracker recorded the subject's field of view and pupil size, and superimposed the gaze position. Fifteen naïve subjects formed a test group; 5 formed a control group. In phase 1, all subjects viewed a sequence of photographic images. In phase 2, the naïve subjects observed a video; in phase 3, they performed computer tasks; in phase 4, the subjects walked around freely. In phase 1, control subjects were instructed to gaze at bright features in the field of view and, in a second test, at dark features. Test group subjects were allowed to gaze freely for all phases. Using the subject's gaze coordinates, we calculated the cumulative light distribution on the retina. As expected for control subjects, cumulative retinal light distributions peaked and dipped in the fovea when they gazed at bright or dark features respectively in the field of view. The light distribution maps obtained from the test group showed a consistent tendency to peak in the macula in phase 3, a variable tendency in phase 4, but little tendency in phases 1 and 2. We conclude that a tendency for light to peak in the macula is a characteristic of some individuals and of certain tasks. In these situations, risk of AMD could be increased but, at the same time, mitigated by the presence of macular carotenoids.

There is ample experimental evidence that polymorphonuclear neutrophils (PMN) play a critical role in the pathogenesis of the adult respiratory distress syndrome (ARDS). Since interleukin-8 (IL-8) is a strong chemotactic factor for PMN, we measured IL-8 levels in plasma and bronchoalveolar lavage (BAL) fluid of 18 patients, 12 with ARDS and 6 with severe pneumonia uncomplicated by ARDS, all of whom had an increased number of PMN in BAL fluid. Seven healthy subjects served as controls. We found elevated levels of IL-8 in the alveolar spaces of all patients tested. Elevated BAL IL-8 levels were related to a fatal outcome and the presence of shock and correlated with a general clinical severity index (simplified acute physiological score). BAL fluid levels of IL-8 were significantly higher in patients with ARDS than in patients with pneumonia. In plasma, IL-8 levels were increased similarly in all patients and did not correlate with survival or the presence of shock. The BAL fluid-to-plasma ratio of IL-8 was significantly greater than that of tumor necrosis factor alpha, indicating higher local production of IL-8. Moreover, the presence of a primed subpopulation of blood PMN with respect to H2O2 production indicates that IL-8 may contribute to the neutrophil-mediated process in the pathogenesis of ARDS and pneumonia.

Vancomycin penetration into the fluid lining the epithelial surface of the lower respiratory tract was studied by performing fiberoptic bronchoscopy with bronchoalveolar lavage on 14 critically ill, ventilated patients who had received the drug for at least 5 days. The apparent volume of epithelial lining fluid (ELF) recovered by bronchoalveolar lavage was determined by using urea as an endogenous marker. Vancomycin levels in ELF ranged from 0.4 to 8.1 micrograms/ml (mean, 4.5 micrograms/ml), while the mean simultaneous level of the drug in plasma was 24 micrograms/ml (range, 9 to 37.4 micrograms/ml). There was a significant relationship (r = 0.64, P < 0.02) between vancomycin levels in plasma and those in ELF, with a correlation whose slope (0.15) indicated that the blood-to-ELF ratio of drug penetration was 6:1. Using the albumin concentration in ELF as a marker of lung inflammation, we found that vancomycin penetration was higher in patients with ELF albumin values of > or = 3.4 mg/ml than in patients with normal values (< 3.4 mg/ml) (P < 0.02). These results suggest that the vancomycin distribution includes the ELF of the lower respiratory tract at a concentration that is dependent upon the levels in blood and the alveolar capillary membrane protein permeability. These concentrations were well above the MICs for most staphylococci and enterococci.

Resume L'infection est l'une des principales complications liees a l'utilisation des catheters. Le traitement curatif des infections sur catheter comporte deux volets: l'attitude vis-a-vis du catheter (retrait, maintien ou echange sur guide), et l'antibiotherapie. Ces deux elements sont lies et leur importance respective varie selon le type de catheter en cause et la situation clinique. L'attitude initiale vis-a-vis d'un catheter central de longue duree chez le malade neutropenique est actuellement volontiers conservatrice, sauf arguments cliniques en faveur d'une infection du tunnel, d'une thrombophlebite septique, ou d'un echec de l'antibiotherapie. Celle-ci doit etre prolongee en regle jusqu'a la sortie d'aplasie. Chez le malade ambulatoire non neutropenique et porteur d'un catheter central de longue duree (nutrition parenterale, chimiotherapie), l'attitude est aussi conservatrice avec les memes limites. L'urgence et la duree de l'antibiotherapie dependent de l'intensite des signes generaux et du microorganisme isole. La technique du “verrou antibiotique” peut etre discutee dans certaines situations. Chez le malade de reanimation porteur d'un catheter central a duree de vie previsible breve (catheters simple ou multiple-lumieres pour surveillance hemodynamique, hemodialyse, nutrition…), le retrait ou l'echange sur guide restent de regle et permettent dans la plupart des cas d'eviter ou de reduire l'antibiotherapie. Dans tous les cas il faut souligner, quelle que soit l'attitude initiale, l'importance de la reevaluation clinique locale et generale, et bacteriologique, a la 48 eme heure.

Resume Les infections representent la premiere cause de deces chez l'hemodialyse chronique. Il s'agit souvent de septicemies dont la porte d'entree la plus frequente est l'abord vasculaire pour hemodialyse. Les staphylocoques, principalement Staphylococcus aureus, mais aussi les staphylocoques a coagulase negative, en sont les principaux micro-organismes responsables. Acinetobacter, Pseudomonas aeruginosa et Candida interviennent plus rarement. Le traitement de premiere intention des septicemies sur fistule arterioveineuse (type Bresciacontrole des taux seriques des antibiotiques. Les associations oxacilline + aminoside et cefamandole + aminoside sont une alternative a cette antibiotherapie de premiere intention. Les septicemies sur catheter ou sur montage vasculaire prothetique doivent beneficier de la meme antibiotherapie, mais le retrait du materiel endovasculaire est souvent necessaire.

Monoclinic zirconia samples were irradiated with 300 MeV Ge and Ni ions at increasing ion fluences. Their structural evolution was monitored in situ by x-ray diffraction and ex situ by Raman spectroscopy. No amorphization of zirconia was observed in both cases. However, a transition from the monoclinic to the tetragonal phase was found in the case of Ge ion irradiation. On the contrary, no such effect was detected upon Ni ion irradiation. A comparison of these experiments indicates that the electronic energy loss released by swift heavy ion irradiation needs to be quite in excess of ∼12 keV nm−1 in order to induce a monoclinic to a tetragonal phase transition in pure (i.e., unstabilized) zirconia.

Resume Dans une serie recente de 87 malades traites pour mediastinite aigue post CEC, le germe en cause etait un Staphylocoque coagulase negative chez 17 patients (19,5%). Dans pres d'un tiers des cas, ce germe etait associe a un autre micro-organisme. L'incidence du caractere de resistance a la meticilline a ete de 53%. Les caracteristiques cliniques de ces mediastinites a staphylocoque coagulase negative sont identiques aux mediastinites dues a d'autres germes, avec cependant une faible incidence de bacteriemie (17%), un âge eleve (66 ans de moyenne) et une mortalite importante (41%). L'antibiotherapie systemique, prolongee associe une β-lactamine et un aminoside lorsque le staphylocoque est meticilline sensible, l'aminoside etant relaye apres 7 a 15 jours de traitement, par une quinolone le plus souvent. Lorsque le staphylocoque est resistant a la meticilline, la vancomycine est associee si possible a 2 autres antibiotiques. Le traitement local ne se distingue pas de celui des autres mediastinites.

Anti-TNFalpha strategies can result in significant clinical benefits in rheumatoid arthritis (RA), but with an increased rate of opportunistic infections. Visceral leishmaniasis (VL) is a severe disease that can develop in immunocompromised hosts, principally in HIV patients. VL in RA patients treated with TNFalpha antagonists is an extremely rare event, and only one case has been described. Here we report a case of VL, occurring after 9 infusions of infliximab in association with azathioprine, in a patient who developed blood cytopenia, fluctuant fever, and splenomegaly.

Introduction Selon les recommandations francaises (AFSSAPS, 2011), il n’est actuellement plus obligatoire de surveiller le taux de plaquettes en cas de prescription d’heparine de bas poids moleculaire (HBPM) a dose preventive en dehors du contexte neoplasique, sous reserve d’une surveillance clinique. Nous rapportons un cas clinique faisant discuter ces recommandations. Observation Une patiente de 67 ans est hospitalisee pour la seconde fois en 10 jours pour une crise d’asthme severe. Un traitement de l’asthme est rapidement debute associe a une HBPM a dose preventive. Apparaissent alors tres rapidement des hematomes diffus et un epistaxis. Le bilan biologique conclut a une CIVD devant un tableau associant thrombopenie (40 000/mm3), fibrinogene abaisse (0,73 g/L), D-dimeres augmentes (> 20 000 ng/mL) et test a l’ethanol positif. Les taux d’haptoglobine et de LDH sont normaux. La recherche d’anticorps (Ac) anti-phospholipides est negative. Du fait d’un court traitement par HBPM a dose preventive 10 jours avant son hospitalisation, le diagnostic de TIH de type 2 est suspecte et confirme par la positivite de la recherche d’Ac anti-PF4 (Elisa) et du test d’agregation plaquettaire, associee a la mise en evidence de thromboses veineuses profondes et d’une embolie pulmonaire. L’enoxaparine est stoppee et remplacee par du danaparoide sodique intraveineux avec pour objectif une activite anti-Xa entre 0,5 et 0,8 UI/mL. Apres 5 jours de traitement par danaparoide les plaquettes ont tres peu augmente, passant de 41 000 a 57 000/mm3. Une reaction croisee entre HBPM et danaporoide sodique est suspectee et un traitement par argatroban IV est alors debute. Les epistaxis cedent rapidement et les hematomes regressent progressivement. Le chiffre des plaquettes remonte a 90 000/mm3 apres 5 jours de traitement et 152 000/mm3 apres 12 jours. Apres la disparition des signes biologiques de CIVD, un traitement par warfarine est alors debute. Le bilan etiologique de CIVD est negatif. Le diagnostic de TIH compliquee de CIVD, secondaire a un traitement par enoxaparine a dose preventive avec allergie croisee avec le danaparoide est retenu. Discussion La TIH est une complication rare (2,6 % des patients traites) mais classique des traitements par HNF ; elle est rarissime au cours des traitements par HBPM (0,2 % des patients traites) [1] . La TIH peut se compliquer de CIVD notamment au cours des TIH de type 2. En effet, Matsuo et al. ont mis en evidence des Ac anti-PF4 chez 14 patients sur 80 pris en charge pour une CIVD : 11 avaient recu un traitement par heparine et 3 avaient presente une diminution du chiffre de plaquettes de plus de 50 % entre 5 et 10 jours apres l’introduction de l’heparine [2] . Conclusion L’observation que nous rapportons est particulierement interessante car meme si les complications rapportees sont rares, elle delivre plusieurs messages didactiques pour les cliniciens : – la TIH peut survenir avec les HBPM utilisees a dose preventive ; – la TIH peut se compliquer de CIVD ; – il faut penser a une reaction d’allergie croisee devant la non correction du chiffre plaquettaire apres arret de l’heparine ou du danaparoide ; – il est necessaire d’attendre la normalisation des plaquettes (> 100 000/mm3) sous danaparoide ou argatroban avant de debuter les AVK, ce qui peut parfois necessiter une dizaine de jours.

Resume La prophylaxie antibiotique de l'endocardite bacterienne est recommandee habituellement lorsque des sujets a risque eleve recoivent des soins dentaires susceptibles d'induire une bacteriemie. Cependant, l'evaluation economique de cette recommandation est l'objet de discussion. Au Royaume Uni, la prophylaxie antibiotique est vraisemblablement beneficiaire de ce point de vue. Ceci merite d'etre evalue en France, compte tenu des differences des pratiques medicales entre ces deux pays.

Resume La pneumopathie a meningocoque, principalement du groupe B en Europe, semble avoir une frequence inferieure a 1 %. Nous en avons rapporte 3 cas observes de facon rapprochee. Ils ont en commun une intoxication ethylo-tabagique au long cours avec une bronchopathie chronique. Dans cette pathologie, la colonisation oropharyngee prealable semble etre le point de depart ; un episode infectieux ORL de type viral peut favoriser la survenue d'une pneumopathie chez un bronchopathe chronique. Le diagnostic est bacteriologique. Neisseria meningitidis est reste sensible a la penicilline, aux amino-penicillines et aux macrolides. La guerison est rapide, sauf si la pneumopathie decompense un mauvais terrain sous-jacent.

Nosocomial pneumonia is a frequent complication in hospitalized patients. Gram-positive pathogens, particularly Staphylococcus aureus, are responsible for the increasing frequency of nosocomial pneumonia. To evaluate the efficacy and safety of intravenous quinupristin/dalfopristin (Synercid) in the treatment of nosocomial pneumonia caused by gram-positive pathogens we conducted a prospective, randomized, open-label, international, multicenter, comparative clinical trial. Two hundred ninety-eight patients with nosocomial pneumonia were enrolled in 74 active centers in five countries: a subgroup of 171 (87 quinupristin/dalfopristin-treated and 84 vancomycin-treated patients) were evaluable for the major efficacy end points. One hundred fifty received 7.5 mg/kg of quinupristin/dalfopristin every 8 h; 148 patients received 1 g of vancomycin every 12 h. Aztreonam at a dose of 2 g every 8 h could be administered in both groups for coverage of gram-negative organisms, and tobramycin was added for coverage against Pseudomonas aeruginosa. The primary efficacy end point was the clinical response between the seventh and the thirteenth day after the end of treatment in clinically evaluable patients with documented causative pathogen(s) at baseline (bacteriologically evaluable population). Therapy was clinically successful (cure or improvement) in 49 (56.3%) of patients receiving quinupristin/dalfopristin and 49 (58.3%) patients receiving vancomycin (difference, -2.0% [95% CI, -16.8% to 12.8%]) in the bacteriologically evaluable population. Equivalent clinical success rates were also observed in the all-treated population (n = 298), and in the bacteriologically evaluable patients intubated in baseline (39/72 [54%] compared with 36/67 [54%]). The by-pathogen bacteriologic response was similar in both treatment groups, with equivalent clinical success rates for Streptococcus pneumoniae, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus. Adverse events (venous and nonvenous) were equally distributed between groups; 15.3% of quinupristin/dalfopristin patients and 9.5% of vancomycin patients discontinued therapy because of an adverse clinical event. In this study quinupristin/dalfopristin was shown to be equivalent to vancomycin in the treatment of nosocomial pneumonia caused by gram-positive pathogens. Quinupristin/dalfopristin merits further evaluation for the treatment of nosocomial pneumonia caused by methicillin-resistant S. aureus.

The infectious complications after lung transplantation have been studied in 26 patients suffering from mucoviscidosis who had transplants in the Ile-de-France between July 1987 and October 1990. We counted 99 infections (74 bacterial infections, 23 viral infections and two fungal infections) during a cumulative observation period of 127 months. The majority of the infections (48%) were localised to the grafted lung. These infections were responsible for 61% of deaths (50% secondary to bacterial infections and 11% to viral infections). The risk of infection remains even after a considerable time after transplantation in this series. These studies underline the importance of infectious complications in the mortality and morbidity of lung transplant patients suffering from mucoviscidosis.

To gain further insight into the pathogenesis of the adult respiratory distress syndrome (ARDS), the authors studied possible relationships among the activation status of circulating polymorphonuclear neutrophils (PMN), cytokine levels, and the severity of lung injury in 31 patients: 15 with ARDS, 9 with severe pneumonia uncomplicated by ARDS, and 7 mechanically ventilated patients with neither ARDS nor pneumonia. Nine healthy subjects served as controls. Using flow cytometry, the authors identified a subpopulation of PMN with an increased capacity to generate hydrogen peroxide after stimulation ex vivo in all three patient groups; significantly higher values were found in those with ARDS. The PMN stimulation index, a reflection of the degree of hyperresponsiveness, correlated with elevated levels of tumor necrosis factor alpha (TNF-alpha) in plasma, and both spontaneous and lipopolysaccharide (LPS)-induced TNF-alpha production by cultured monocytes. These biological expressions of PMN activation and cytokine generation both correlated with indices of the severity of lung injury, but not with the overall clinical severity. In contrast, IL-6 and IL-1 beta showed little or no relationship with either the degree of lung injury or PMN hyperresponsiveness. We conclude that TNF alpha-primed PMN may play a major role in the pathogenesis of ARDS-associated lung injury.

From January 1978 to December 1988, 71 patients underwent surgical intervention at our institution for prosthetic valve endocarditis with ring abscesses. These procedures involved 59 aortic prostheses and 12 mitral prostheses. No causative agent could be identified in 19 patients (26.7%). The operation was performed during antibiotic therapy in 63 patients and after a planned course of antibiotic therapy in 8 patients. At the aortic level, abscesses were remedied by suturing in 3 cases, by pericardial patches in 34 cases, and by complex procedures in 22 cases (subcoronary valved conduit in 11 cases, supracoronary valved conduit with coronary bypass grafts in 10 cases, apicoaortic valved conduit in 1 case). At the mitral level, ring abscesses were cured in 10 cases by intraatrial implantation of the prosthesis. In one case, the prosthesis was anchored inside the left ventricle; and in one case the valve could be seated on the anulus. The overall operative mortality rate was 17%. Long-term survival was 54% +/- 8% at 6 years. Fifteen (26%) of the survivors needed a third valve replacement (four operative deaths); a complex reconstruction was performed in seven patients. Better detection of ring abscesses and earlier surgical intervention before annular destruction and hemodynamic failure can improve the operative mortality rate for prosthetic valve endocarditis. When it is necessary, complex reconstruction, in spite of a high mortality rate, seems to eradicate the infectious seat, and the outlook for the patient's condition appears good.

Nosocomial pneumonia is a frequent complication in hospitalized patients. Gram-positive pathogens, particularly Staphylococcus aureus, are responsible for the increasing frequency of nosocomial pneumonia. To evaluate the efficacy and safety of intravenous quinupristin/dalfopristin (Synercid) in the treatment of nosocomial pneumonia caused by gram-positive pathogens we conducted a prospective, randomized, open-label, international, multicenter, comparative clinical trial. Two hundred ninety-eight patients with nosocomial pneumonia were enrolled in 74 active centers in five countries: a subgroup of 171 (87 quinupristin/dalfopristin-treated and 84 vancomycin-treated patients) were evaluable for the major efficacy end points. One hundred fifty received 7.5 mg/kg of quinupristin/dalfopristin every 8 h; 148 patients received 1 g of vancomycin every 12 h. Aztreonam at a dose of 2 g every 8 h could be administered in both groups for coverage of gram-negative organisms, and tobramycin was added for coverage against Pseudomonas aeruginosa. The primary efficacy end point was the clinical response between the seventh and the thirteenth day after the end of treatment in clinically evaluable patients with documented causative pathogen(s) at baseline (bacteriologically evaluable population). Therapy was clinically successful (cure or improvement) in 49 (56.3%) of patients receiving quinupristin/dalfopristin and 49 (58.3%) patients receiving vancomycin (difference, -2.0% [95% Cl, -16.8% to 12.8%]) in the bacteriologically evaluable population. Equivalent clinical success rates were also observed in the all-treated population (n = 298), and in the bacteriologically evaluable patients intubated in baseline (39/72 [54%] compared with 36/67 [54%]). The by-pathogen bacteriologic response was similar in both treatment groups, with equivalent clinical success rates for Streptococcus pneumoniae, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus. Adverse events (venous and nonvenous) were equally distributed between groups; 15.3% of quinupristin/dalfopristin patients and 9.5% of vancomycin patients discontinued therapy because of an adverse clinical event. In this study quinupristin/dalfopristin was shown to be equivalent to vancomycin in the treatment of nosocomial pneumonia caused by gram-positive pathogens. Quinupristin/dalfopristin merits further evaluation for the treatment of nosocomial pneumonia caused by methicillin-resistant S. aureus.

One hundred seven acutely ill ventilated patients were prospectively studied to ascertain the severity and frequency of alterations in gas exchange and hemodynamic parameters during brief bronchoscopy. Sedation was performed using midazolam (0.1 mg/kg IV) without topical anesthesia. An average decline in PaO2 of 26 percent was observed at the end of the procedure, compared to the baseline value, and this was associated with a mild increase in PaCO2 in spite of the use of a special adapter. Alterations in mean systolic blood pressure appeared to be modest, consisting of a 10 percent decrease from the control level, related to sedation, and a 10 percent rise from baseline during the procedure, associated with a concomitant mild tachycardia. At that time, central hemodynamic measurements performed in a subset of 31 patients showed a significant increase in cardiac output associated with higher pulmonary wedge pressure. Fourteen patients developed hypoxemia of less than 60 mm Hg on FIO2 adjusted to 0.8. Of the ten risk factors univariately associated with hypoxemia, only the presence of ARDS (p less than 0.001) and "fighting" the ventilator during the procedure (p less than 0.05) remained significant after stepwise logistic regression. Attempts to prevent hypoxemia in critically ill patients should focus on inducing complete sedation, with careful attention to hemodynamic status, or providing maximal levels of oxygen to the ventilator (or both).

The pharmacokinetics of teicoplanin were studied in 15 adult patients in the acute phase of severe infections caused by gram-positive cocci. All the subjects were given a daily intravenous bolus dose of 6 mg of teicoplanin kg-1 (body weight). The pharmacokinetic study was performed over a 48-h period after injection 4. The subjects were categorized according to their mean creatinine clearances (ml.min-1.kg-1) during the study period: group 1 (n = 3), greater than 1.6; group 2 (n = 6), 0.8 to 1.6; and group 3 (n = 6), 0.15 to 0.8. Mean concentrations of teicoplanin in serum at 1, 24, and 48 h were 33 +/- 8, 9 +/- 3, and 6 +/- 2.5 micrograms.ml-1, respectively. The mean half-lives of the concentration-time curve from 12 to 48 h were 28 +/- 4, 44 +/- 24, and 48 +/- 14 h in groups 1, 2, and 3, respectively (group 3 versus group 1: P less than 0.05). The mean area under the serum concentration-time curve from time zero to 24 h was 344 +/- 92 mg.h.liter-1, and the mean hybrid volume of distribution was 1.09 +/- 0.46 liter.kg-1. These values were similar for the three groups, with a trend for larger areas under the curve in group 3. Creatinine clearance correlated directly with the total body clearance of teicoplanin (r = 0.70) and with the renal clearance of teicoplanin (r = 0.82). However, in critically ill patients, the wide interindividual variations in pharmacokinetic parameters are more relevant than those related to the variations in renal function when creatinine clearance is above 0.30 ml.min-1.kg-1. We concluded that, in such conditions, monitoring of concentrations of teicoplanin in serum is mandatory.

The effect of short-term antibiotic prophylaxis on postoperative infection with 2 injections of cefotaxime begun preoperatively was evaluated in a double-blind, randomized, placebo-controlled trial at 1 center on 181 patients with preoperative sterile urine undergoing transurethral resection (90) or open prostatectomy (91). Antibiotic prophylaxis reduced the number of urinary infections significantly in both groups without altering the level of resistant pathogens. Cefotaxime lowered the incidence of postoperative infection in the early postoperative period from 30 to 4 per cent in the transurethral resection group and from 46 to 4.5 per cent in the open prostatectomy group. A significant difference was found between the 2 treatment groups in the incidence of perioperative bacteremia and postoperative fever. Among the patients undergoing an open prostatectomy a reduced rate of wound infection and a shorter duration of hospital stay were witnessed in the treated group. Thus, short-term chemoprophylaxis by cefotaxime is of benefit in reducing morbidity and hospital cost for prostatectomy by either procedure.