Impact of a five-year surveillance of central venous catheter infections in the REACAT intensive care unit network in France.

Central venous catheter (CVC)-related infections (CRIs) are a key target for infection control in intensive care units (ICUs). The aim of this study was to describe temporal trends of CRI incidence in a network of volunteer ICUs in Northern France. During a 4 month surveillance period each year, all CVCs in place for more than 48h were prospectively followed until removal or patient discharge. Standard clinical and microbiological criteria were used to define colonization and CRI. The standardized incidence ratio (SIR) was estimated by dividing the number of observed CRIs by the number of expected CRIs, which was computed using a logistic regression model including risk factors for CRI. CRI incidence and SIR were fed back to ICUs as a benchmark at the end of each period. From 2001 to 2005, 135 ICUs participated for at least one surveillance period. Overall, 11 703 CVC in 9182 patients (122 495 CVC-days) were included. CRI incidence was 2.8 per 1000 CVC-days. Among 35 ICUs that participated for three or more consecutive periods, CRI incidence decreased significantly by 58.6%. SIR also decreased significantly from the first to the third surveillance period in these ICUs. These results suggest that surveillance programmes have a significant impact on CRI risk in ICUs and remain an important strategy for combating nosocomial infections in these settings.

Hepatopoietin A: partial characterization and trypsin activation of a hepatocyte growth factor.

Rat hepatocytes in primary culture are stimulated to synthesize DNA by high-molecular-weight fractions from rat serum. This activity has been previously given the name hepatopoietin A (HPTA). HPTA, with an apparent molecular weight of 150,000 to 250,000, stimulated the incorporation of [3H]thymidine into DNA, quantitated by autoradiography as percentage of nuclear labeling. Properties of HPTA include: sensitivity to heat; stability in minimal essential media at 4 degrees C; in lyophilized form; or in 25% glycerol at -20 degrees C; and instability at 4 degrees C in isotonic buffer. Trypsin digestion of HPTA resulted in an increase in biological activity. Both the trypsinized and native forms of this activity were not inhibited by antiserum against mouse epidermal growth factor in this bioassay. Treatment of HPTA with trypsin resulted in a shift of its apparent molecular weight on a Sephadex G-50 column to less than 6000. This trypsinized HPTA activity did not comigrate with 125I-labeled epidermal growth factor on the same column. These results demonstrate that HPTA exists in normal serum as a large precursor to a more active moiety, generated by proteolytic cleavage, which is not identical to epidermal growth factor. Fractions from human serum and plasma of molecular weight similar to that of HPTA have also been shown to stimulate DNA synthesis in rat hepatocytes.

Obsessive-compulsive disorders: a review of the literature.

The authors reviewed the studies on obsessive-compulsive disorders published from 1953 to 1978. They report on various theories of the etiology of the disorders and provide an overview of the studies based on these theories. The treatment modalities covered include behavioral modification, drug therapy psychotherapy, surgery, and experimental therapies. the authors conclude that, although the obsessive-compulsive disorders are widely present, there is a paucity of new data concerning their treatment. The evidence to date, however, suggests that psychotherapy is an essential ingredient in the treatment process. They recommended that further clinical studies be done to elucidate the etiology and treatment of these disorders.

Mediastinitis due to Nocardia asteroides after cardiac transplantation.

Nocardia infection classically occurs in immuno-compromized patients. Only a few cases of mediastinal infection due to this pathogen have been described in the literature. We report a patient who developed mediastinitis due to Nocardia asteroides after cardiac transplantation. The treatment was surgical debridement, dressing, sugaring and antibiotic therapy. The emergence of a severe acute renal failure possibly induced by drug interaction between Cyclosporin, cyclines and aminoglycosides, led us to modify the antimicrobial treatment. The intravenous use of Imipenem 2 g per day and Ciprofloxacin 400 mg per day for four weeks and then oral Ciprofloxacin 1.5 g per day for 1 year, was effective and allowed a good outcome, without any drug interaction with Cyclosporin, adverse effect, graft rejection episode or infection relapse.

[Idiopathic retroperitoneal fibrosis disclosed by nephrogenic diabetes insipidus]. / Fibrose rétropéritonéale idiopathique révélée par un diabète insipide néphrogénique.

Nephrogenic diabetes insipidus is an exceptional complication of incomplete ureteric obstruction with hydronephrosis. We report one case of this condition revealing idiopathic retroperitoneal fibrosis. Pathogenic mechanisms are discussed.

[A simplified severity index in resuscitation. Validation by a prospective study (280 cases)]. / Un indice de gravité simplifié en réanimation. Validation par une étude prospective (280 cas).

The index studied (simplified acute physiology score, or SAPS) is calculated from 14 measurable clinical and laboratory data obtained during the first 24 hours from admission. It was tested in a prospective study involving 280 consecutive patients treated in a 16-bed intensive care unit. Good correlations were found between SAPS and mortality rate and between SAPS and the two most widely used scoring systems: the Knaus index or APS (acute physiology score) and the Cullen index or TISS (therapeutic intervention scoring system), both evaluating therapeutic effectiveness. SAPS data being easy to collect, the simplified index could be used in many intensive care units or even applied to old case-records. Its main value lies in comparisons between two groups of patients with the same death probability and in evaluations of activities in intensive care units.

[Simultaneous detection by multiplex PCR of atypical bacterial pathogens involved in infections of respiratory tract. Is it useful for the microbiological diagnosis of respiratory infections]. / La détection par une PCR multiplex de bactéries responsables de pneumopathies atypiques améliore-t-elle les performances du diagnostic microbiologique des infections du tractus respiratoire?

The aim was to evaluate the "strategical place" of the new commercial test Chlamylege (Argene-Biosoft-France) which allows the simultaneous detection in respiratory samples of Chlamydophila pneumoniae, Mycoplasma pneumoniae and most Legionella species using a PCR multiplex. 41 patients with an atypical pneumonia were included, all standard procedures of diagnosis were done and in addition the chamylege test. A pathogen was identified in 12 patients, an other microorganisms than the 3 targeted by our study was found in 8 patients. 4 positive PCR were obtained, 3 with M. pneumoniae and 1 with Legionella pneumophila 1. That means that for 29 patients no aetiology was found. Among them 23 clearly improved under antibiotic treatment. Though that PCR multiplex is an attractive test, easy to perform, sensitive, specific and convenient, we need further studies to approach the place of this PCR test in the diagnosis of multifaceted atypical pneumonia. We also need to know if the cost associated with the microbiological diagnosis (culture, serology, immunofluorescence, urinary antigen test, PCR...) for atypical pneumonia worth value? An algorithm as to be drawn to determine the value of intensive microbiological investigation. An other point to discuss, may be this kind of rapid and multiplex PCR technique could lead to spare the use of some antibiotics.

Concentrations of 2-hydroxyoestrogens in human sera measured by a heterologous immunoassay with an 125I-labelled ligand.

A heterologous immunoassay for 2-hydroxyoestrogens has been established in which antibodies raised against 2-hydroxyoestradiol-17-succinyl-BSA serve as binding protein and 2-hydroxyoestrone-17-cmo-[125I]iodohistamine as radioligand. Lipophilic serum components competing for binding sites in this system were defined as total 2-hydroxyoestrogens'. The underlying assumption of specificity was supported by the pattern of cross-reactivity evaluated with structural related steroids and o-diphenols and by the fact, that an additional chromatography of the serum extracts preceding the competing reaction had little if any effect. Sensitivity: 2.8 +/- 1 pg/tube; accuracy: Y = 0.91x + 2.2; r = 0.989; precision: 5.8% intra-assay; 6.5% inter-assay. The following concentrations (+/- standard deviation) were found in the sera of healthy subjects. Young men: 29 +/- 5 pg/ml (n = 11); women follicular phase: 32 +/- 8 pg/ml (n = 25); luteal phase: 53 +/- 13 pg/ml (n = 23); postmenopausal women: 13 +/- 4 pg/ml (n = 10); pregnant women 11th--20th week: 70 +/- 16 mg/ml (n = 64); 36th--40th week: 240 +/- 23 pg/ml (n = 40); newborn cord blood: 604 +/- 43 pg/ml (n = 48).

Zinc(II) complexes of tripodal peptides mimicking the zinc(II)-coordination structure of carbonic anhydrase.

Two new tripodal peptide ligands with histidine side chains have been synthesized and were shown to form stable zinc(II) complexes. Their NMR and mass spectra indicate a structure that is analogous to the active center of carbonic anhydrase. Both the ligands and the zinc complexes were titrated potentiometrically in order to obtain the pKa values for the coordinated water of the zinc complexes; due to the low solubility of the complexes only estimates could be obtained.

Alpha-synuclein and Parkinson's disease: selective neurodegenerative effect of alpha-synuclein fragment on dopaminergic neurons in vitro and in vivo.

Missense mutations in the alpha-synuclein gene were associated with a familial Parkinson's disease, and alpha-synuclein is a major component of Lewy bodies, the intracellular inclusions that neuropathologically characterize Parkinson's disease. We investigated the neurotoxic activity of the nonamyloid component (NAC) of senile plaque, the fibrillogenic fragment (61-95) of alpha-synuclein, in vitro and in vivo. Rat primary mesencephalic neurons were exposed for 6 days to low concentrations of preaggregated NAC (0.5-10.0 microM). The number of dopaminergic neurons and dopamine content were both reduced with no effect on the general viability of the cells. At higher concentrations (25-100 microM), the neurotoxic effect of NAC was extended to all neurons. Preaggregated NAC was also toxic on a PC12 dopaminergic cell line differentiated with nerve growth factor. The intracellular localization of NAC has been identified by the exposure of neuronal cells to fluorescent peptide. In vivo application of aggregated NAC in the substantia nigra induced loss of dopaminergic neurons. Our data illustrate the selective neurotoxic effect of NAC for dopaminergic neurons and support the central role of alpha-synuclein in the pathogenesis of Parkinson's disease.

Simplified acute physiology score II for measuring severity of illness in intermediate care units.

OBJECTIVES: To assess the efficacy of the Simplified Acute Physiology Score (SAPS II) in intermediate care units. A number of patients hospitalized in the intensive care unit (ICU) could be hospitalized in alternative structures, intermediate care units, which are equipped to handle their monitoring needs and able to provide adequate treatment at a lower cost. Characterization of the patients relies on the assessment of their severity of illness by severity scores. The efficiency of severity scores has been established in ICU patients, but not in the setting of intermediate care units. DESIGN: Prospective study. SETTING: Intermediate care unit of a multidisciplinary hospital. PATIENTS: Four hundred thirty-three patients admitted to the intermediate care unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 561 consecutive patients admitted to the intermediate care unit during a 12-mo period, 433 patients could be included in the analysis. Patients were admitted from the emergency ward (60.9%). Of the study patients, 60.9% were admitted from the emergency ward for mostly (96%) medical reasons. Average length of stay was 3.1 +/- 2.3 (SD) days. Death rate in the intermediate care unit was 2.7% (n = 11). Average SAPS II was 22.3 +/- 12.0 (range 6 to 73). Hospital death rate was 8.1%, whereas the expected mortality rate derived from SAPS II was 8.7%. To assess the performance of the system, a formal goodness-of-fit test was performed to evaluate calibration. Calibration was accurate using the C coefficient of Hosmer-Lemeshow statistics (C = 2.4; p> 0.5). The discriminant power of SAPS II, measured by the area under the receiver operating characteristic curve was excellent (0.85 +/- 0.04). CONCLUSIONS: The SAPS II assessment of severity of illness in patients admitted to an intermediate care unit is reliable. These results will need to be confirmed, using different patient samplings from intermediate care units.

[Microbiological diagnosis of bacteremia from a catheter: a simple method? Results of a retrospective study]. / Diagnostic microbiologique de bactériémie liée à une chambre implantable: une méthode simple? Résultats d'une étude rétrospective.

Diagnosing catheter-related bloodstream infections is important but not always easy and a failure to make the diagnosis may have serious consequences. A high rate of unnecessary catheter removal is noted. We retrospectively compared the clinical and usual methods of microbiological diagnoses of catheter-related sepsis to the speed of detection of the catheter versus peripheral blood cultures using the Bact-Alert system. We analyzed 50 files of patients with central indwelling devices: 16 single lumen catheters and 34 implanted ports. Twenty-one catheters were classified as infected, and we observed an earlier positivity of catheter versus peripheral blood in all cases, but significant for 19 patients. According to standard diagnosis methods, 29 catheters were estimated non-infected, a more rapid detection of peripheral culture was reported for 17 specimens and, for another eight patients, the time of detection was equal to blood culture drawn from the catheter. In this group, four discrepancies were recorded with a differential time in favor of sepsis related to catheters ranging from 0.5 to 2 hours. Because of its simplicity and low cost, we believed that this method could be the first step of a diagnosis of catheter-related sepsis and could, therefore, avoid unjustified removal, in particular for the implanted ports for which the diagnostic methods are less codified than for catheters. A prospective study is ongoing; the design of the study focuses only on implanted ports.

Fluconazole penetration in cerebral parenchyma in humans at steady state.

We studied fluconazole penetration in the brain in five patients who had a deep cerebral tumor whose removal required the excision of healthy brain tissue. Plasma and brain samples were simultaneously obtained after oral ingestion of 400 mg of fluconazole daily for 4 days (90% of steady state). Fluconazole penetration in healthy cerebral parenchyma was determined. Plasma and brain samples were assayed by high-pressure liquid chromatography. Concentrations in plasma and brain tissue were 13.5 +/- 5.5 micrograms/ml and 17.6 +/- 6.6 micrograms/g, respectively. The average ratio of concentrations in the brain and plasma (four patients) was 1.33 (range, 0.70 to 2.39). Despite the lack of data concerning the penetration of fluconazole in brain abscesses, these results should permit the use of a daily dose of 400 mg of fluconazole in prospective clinical studies that evaluate the effectiveness of this drug in the treatment of brain abscesses due to susceptible species of fungi.

Differential effect of growth factors on growth stimulation and phenotypic stability of glutamine-synthetase-positive and -negative hepatocytes in primary culture.

In rat liver parenchyma, two subpopulations of hepatocytes can be distinguished by the absence or presence of the marker enzyme, glutamine synthetase (GS). Hepatocytes in the perivenous zone immediately adjacent to the hepatic venules in the liver acinus are positive for GS. Using autoradiography in combination with immunocytochemistry, the response of these two hepatocyte populations (GS positive and GS negative) to a variety of growth factors (defined compounds or complex stimuli) was investigated in vitro. Irrespective of the individual growth-promoting activity (which varied considerably), all stimuli led to much higher labeling indices in GS-negative cells as compared to GS-positive cells. In GS-negative cells, the strongest effect was exerted by serum obtained from partially hepatectomized rats (labeling index, 67%) and the conditioned media of JM1 and JM2 hepatoma cells (63%-82%), followed by a combination of insulin and either norepinephrine (46%) or epidermal growth factor (EGF; 42%). In contrast, serum had the weakest influence on GS-positive cells (0.3%), while the other potent stimuli enhanced the labeling index of these cells by between 6% and 15% within 48 h. The percentage of labeled nuclei was higher in mononucleated than in binucleated GS-positive hepatocytes. The time course of thymidine incorporation was also different for the two subpopulations. Under all growth-promoting conditions, the stimulation of GS-negative cells peaked between 72 and 96 h, while it increased continuously in GS-positive cells for at least 120 h, particularly in the case of serum. In proliferating cultures, both the absolute and the relative number of GS-positive hepatocytes decreased, while no such effect was found in various nonproliferating control cultures maintained at low and high cell density. Similar results were found for GS activity. In contrast, the hormonal induction of tyrosine aminotransferase (TAT) was not affected. It is suggested that these differences in the growth response of GS-positive and -negative cells contribute to the acinar gradient in hepatocyte proliferation that occurs during liver regeneration. Furthermore, the striking phenotypic instability of GS-positive cells that have undergone DNA synthesis and mitosis supports the hypothesis that cellular reprogramming depends on passage through the cell cycle.

Copper(I) complexes, copper(I)/O(2) reactivity, and copper(II) complex adducts, with a series of tetradentate tripyridylalkylamine tripodal ligands.

Copper(I) and copper(II) complexes possessing a series of related ligands with pyridyl-containing donors have been investigated. The ligands are tris(2-pyridylmethyl)amine (tmpa), bis[(2-pyridyl)methyl]-2-(2-pyridyl)ethylamine (pmea), bis[2-(2-pyridyl)ethyl]-(2-pyridyl)methylamine (pmap), and tris[2-(2-pyridyl)ethyl]amine (tepa). The crystal structures of the protonated ligand H(tepa)ClO(4), the copper(I) complexes [Cu(pmea)]PF(6) (1b-PF(6)), [Cu(pmap)]PF(6) (1c-PF(6)), and copper(II) complexes [Cu(pmea)Cl]ClO(4).H(2)O (2b-ClO(4).H(2)O), [Cu(pmap)Cl]ClO(4).H(2)O (2c-ClO(4).H(2)O), [Cu(pmap)Cl]ClO(4) (2c-ClO(4)), and [Cu(pmea)F](2)(PF(6))(2) (3b-PF(6)) were determined. Crystal data: H(tepa)ClO(4), formula C(21)H(25)ClN(4)O(4), triclinic space group P1, Z = 2, a = 10.386(2) A, b = 10.723(2) A, c = 11.663(2) A, alpha = 108.77(3) degrees, beta = 113.81(3) degrees, gamma = 90.39(3) degrees; 1b-PF(6), formula C(19)H(20)CuF(6)N(4)P, orthorhombic space group Pbca, Z = 8, a = 14.413(3) A, b = 16.043(3) A, c = 18.288(4) A, alpha = beta = gamma = 90 degrees; (1c-PF(6)), formula C(20)H(22)CuF(6)N(4)P, orthorhombic space group Pbca, Z = 8, a = 13.306(3) A, b = 16.936(3) A, c = 19.163(4) A, alpha = beta = gamma = 90 degrees; 2b-ClO(4).H(2)O, formula C(19)H(22)Cl(2)CuN(4)O(5), triclinic space group P1, Z = 4, a = 11.967(2) A, b = 12.445(3) A, c = 15.668(3) A, alpha = 84.65(3) degrees, beta = 68.57(3) degrees, gamma = 87.33(3) degrees; 2c-ClO(4).H(2)O, formula C(20)H(24)Cl(2)CuN(4)O(5), monoclinic space group P2(1)/c, Z = 4, a = 11.2927(5) A, b = 13.2389(4) A, c = 15.0939(8) A, alpha = gamma = 90 degrees, beta = 97.397(2) degrees; 2c-ClO(4), formula C(20)H(22)Cl(2)CuN(4)O(4), monoclinic space group P2(1)/c, Z = 4, a = 8.7682(4) A, b = 18.4968(10) A, c = 13.2575(8) A, alpha = gamma = 90 degrees, beta = 94.219(4) degrees; 3b-PF(6), formula [C(19)H(20)CuF(7)N(4)P](2), monoclinic space group P2(1)/n, Z = 2, a = 11.620(5) A, b = 12.752(5) A, c = 15.424(6) A, alpha = gamma = 90 degrees, beta = 109.56(3) degrees. The oxidation of the copper(I) complexes with dioxygen was studied. [Cu(tmpa)(CH(3)CN)](+) (1a) reacts with dioxygen to form a dinuclear peroxo complex that is stable at low temperatures. In contrast, only a very labile peroxo complex was observed spectroscopically when 1b was reacted with dioxygen at low temperatures using stopped-flow kinetic techniques. No dioxygen adduct was detected spectroscopically during the oxidation of 1c, and 1d was found to be unreactive toward dioxygen. Reaction of dioxygen with 1a-PF(6), 1b-PF(6), and 1c-PF(6) at ambient temperatures leads to fluoride-bridged dinuclear copper(II) complexes as products. All copper(II) complexes were characterized by UV-vis, EPR, and electrochemical measurements. The results manifest the dramatic effects of ligand variations and particularly chelate ring size on structure and reactivity.