In Vitro Induction of Human Regulatory T Cells Using Conditions of Low Tryptophan Plus Kynurenines.

Thymic regulatory T cells (tTregs) and induced regulatory T cells (iTregs) suppress murine acute graft-versus-host disease (GVHD). Previously, we demonstrated that the plasmacytoid dendritic cell indoleamine 2,3-dioxygenase (IDO) fosters the in vitro development of human iTregs via tryptophan depletion and kynurenine (Kyn) metabolites. We now show that stimulation of naïve CD4+ T cells in low tryptophan (low Trp) plus Kyn supports human iTreg generation. In vitro, low Trp + Kyn iTregs and tTregs potently suppress T effector cell proliferation equivalently but are phenotypically distinct. Compared with tTregs or T effector cells, bioenergetics profiling reveals that low Trp + Kyn iTregs have increased basal glycolysis and oxidative phosphorylation and use glutaminolysis as an energy source. Low Trp + Kyn iTreg viability was reliant on interleukin (IL)-2 in vitro. Although in vivo IL-2 administration increased low Trp + Kyn iTreg persistence on adoptive transfer into immunodeficient mice given peripheral blood mononuclear cells to induce GVHD, IL-2-supported iTregs did not improve recipient survival. We conclude that low Trp + Kyn create suppressive iTregs that have high metabolic needs that will need to be addressed before clinical translation.

Clinical and microbiological features of Clostridium difficile infections in France: the ICD-RAISIN 2009 national survey.

INTRODUCTION: The surveillance of Clostridium difficile infections (CDI) in France was reinforced after the emergence of the PCR-ribotype 027 epidemic clone in 2006; notification of case clusters or severe cases by healthcare facilities (HCF) became mandatory. The French Public Health Surveillance Institute (InVS) and the C. difficile National Reference Center (NRC) launched a national, prospective, multicentric survey to complete available data, in 2009. The survey had for objectives to assess CDI incidence and to characterize the strains responsible for CDI. PATIENTS AND METHODS: Every month from March to August 2009, HCF notified the total number of new CDI cases, admissions, and patient-days (PD) to the InVS. A subset of participating HCF sent strains, isolated in March 2009 from CDI patients, to the NRC. RESULTS: One hundred and five HCF with acute care wards and 95 with rehabilitation/long-term care (RLTC) wards participated in the 6-month epidemiological study. The incidence of CDI was 2.28 or 1.15 cases per 10,000 PD in acute care (n=1316 cases) or RLTC (n=295 cases), respectively. Seventy-eight HCF participated in the microbiological study. Two hundred and twenty-four (94.9%) of the 236 strains received by the NRC were toxigenic. The five major PCR-ribotypes were 014/020/077 (18.7%), 078/126 (12.1%), 015 (8.5%), 002 (8%), and 005 (4.9%). CONCLUSION: The incidence of CDI in 2009 in France remained lower than in other European countries, suggesting a successful impact of the 2006 recommendations for CDI control.

In vitro antibacterial activity of doripenem against clinical isolates from French teaching hospitals: proposition of zone diameter breakpoints.

The aims of the study were to determine the in vitro activity of doripenem, a new carbapenem, against a large number of bacterial pathogens and to propose zone diameter breakpoints for clinical categorization in France according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) minimum inhibitory concentration (MIC) breakpoints. The MICs of doripenem were determined by the broth microdilution method against 1,547 clinical isolates from eight French hospitals. The disk diffusion test was performed (10-µg discs) according to the Comité de l'Antibiogramme de la Société Française de Microbiologie (CASFM) method. The MIC(50/90) (mg/L) values were as follows: methicillin-susceptible Staphylococcus aureus (MSSA) (0.03/0.25), methicillin-resistant Staphylococcus aureus (MRSA) (1/2), methicillin-susceptible coagulase-negative staphylococci (MSCoNS) (0.03/0.12), methicillin-resistant coagulase-negative staphylococci (MRCoNS) (2/8), Streptococcus pneumoniae (0.016/0.25), viridans group streptococci (0.016/2), ß-hemolytic streptococci (≤0.008/≤0.008), Enterococcus faecalis (2/4), Enterococcus faecium (128/>128), Enterobacteriaceae (0.06/0.25), Pseudomonas aeruginosa (0.5/8), Acinetobacter baumannii (0.25/2), Haemophilus influenzae (0.12/0.25), and Moraxella catarrhalis (0.03/0.06). According to the regression curve, the zone diameter breakpoints were 24 and 19 mm for MICs of 1 and 4 mg/L, respectively. This study confirms the potent in vitro activity of doripenem against Pseudomonas aeruginosa, Acinetobacter, Enterobacteriaceae, MSSA, MSCoNS, and respiratory pathogens. According to the EUCAST MIC breakpoints (mg/L) ≤1/>4 for Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter, and ≤1/>1 for streptococci, pneumococci, and Haemophilus, the zone diameter breakpoints could be (mm) ≥24/<19 and ≥24/<24, respectively.

The role of cocaine in fatal crashes: first results of the Québec drug study.

As part of a major undertaking to establish the contribution of drugs in road crashes in Quebec, the present study focuses on the role of cocaine. Coroner, forensic laboratory and police accident records from April 1999 to December 2000 were matched for 265 fatally injured drivers of passenger vehicles. Cocaine was found in 7.9% of urine samples and 6.0% of blood samples. In order to set up a control group, two roadside surveys were conducted in August 1999 and 2000. The survey sample was distributed proportionately to the number of fatal accidents per time of day and day of the week. During both daytime and nighttime, a total of 11,952 drivers participated in the two surveys among which 11,574 provided a breath sample (96.8%), 8,177 a saliva sample (68.4%) and 5,931 a urine sample (49.6%). Cocaine was detected in 1.1% of urine samples and 1.0% of saliva samples of the driving population. In both fatally injured drivers and driving population, cocaine was found mostly (> 90%) in four main types of combination: cocaine alone, cocaine + cannabis, cocaine + alcohol, cocaine + cannabis + alcohol. The data collected allowed two different analyses: a case-control (urine/urine) and a responsibility analysis (case-case approach) that compares cocaine cases to drug-free cases. Despite some data limitations, all analyses for the four main types of combination clearly suggest that cocaine use plays a role in fatal crashes.

[Calf muscle venous thrombosis and pulmonary embolism]. / Thrombose veineuse musculaire du mollet et embolie pulmonaire.

INTRODUCTION: The clinical significance of calf muscle venous thrombosis (CMVT) still remains a matter of debate. Detected by ultrasonography, they are overlooked by venography. This prompted us to evaluate the frequency of such localizations and their association to pulmonary embolism (PE). METHODS: Retrospective review of our database over a three-year period. All patients with an isolated CMVT were included. RESULTS: Isolated CMVT were detected in 106 patients (mean age 68.6 years; 65% women), that is 12.5% of all venous thromboses diagnosed in the vascular sonography unit over the study period Sixteen associated PE were detected (15%). CONCLUSIONS: Association of CMVT and PE is not infrequent. Whether or not such thromboses have the potential to extend into deep veins and/or to migrate into pulmonary circulation requires further studies.

[Pulmonary embolism and unusual deep venous thrombosis. Report of two cases]. / Embolies pulmonaires et thromboses veineuses profondes inhabituelles. A propos de deux observations.

Contrast venography is the gold standard for the diagnosis of deep vein thrombosis in the lower limb extremities, but it fails to visualize deep veins like deep femoral vein and internal iliac vein. The internal iliac can be examined with duplex scanning if the technique and the examination conditions are correct. As reported in these two cases, thrombosis of these deep veins may lead to pulmonary embolism. The first case is a young female with venous thromboembolic disease in whom internal iliac vein thrombosis was documented only at the second examination. In the second case, deep femoral vein thrombosis appeared early in a comatose young male. This thrombosis may be classified as proximal muscular vein thrombosis. These two cases emphasize the importance of a duplex scanning examination performed with rigorous technique, whose the main limitation being examination conditions.

Care planning in home care: an exploratory study.

Care Planning is one of the most important responsibilities of the case manager in home care. Research on how care plan decisions are made is scarce in the case management literature. The purpose of this exploratory study was to determine the factors that influence the decision-making process of case managers within the Edmonton Home Care Program (EHCP) when developing care plans. A volunteer sample of six EHCP case managers from three different disciplines was selected: two registered nurses (BScN), two occupational therapists (BScoT), and two social workers (BSW). With the use of fictional case studies, these professionals were asked to construct care plans. Individual semi-structured interviews and a group session permitted in-depth exploration of their decision-making process. Findings suggest that client and/or caregiver characteristics appear to be the most influential in determining care plans. It was also found that case managers are not comfortable with fiscal accountability.

Blunt abdominal trauma in children: the practical value of ultrasonography.

The occult nature of blunt abdominal trauma justifies the need for reliable diagnostic adjuncts to physical examination. From June 1988 to June 1991, 259 children admitted to the general surgery/trauma service underwent abdominal ultrasonographic scanning (US). A total of 116 abdominal lesions were found in 81 patients. Ultrasonography alone had a sensitivity of 89%, a specificity of 96%, and an overall accuracy of 94%, as determined against the overall diagnostic workup and clinical course (mean follow-up, 17.4 weeks). In 44% of the patients, US was used alone; in 49% one or two additional tests were performed, and in only 7% were three or more tests required. Compared with computed tomography, US is more versatile, easier to perform in children, and more cost effective, even with the addition of a functional imaging modality. Although not demonstrated by this preliminary, retrospective study, Doppler US appears to be the logical complement to abdominal ultrasonography in the evaluation of children with blunt abdominal trauma.

Opposite effects of neuropeptide Y (NPY) and polypeptide YY (PYY) on plasma immunoreactive atrial natriuretic factor (IR-ANF) in rats.

Female Sprague-Dawley rats were administered NPY and PYY in doses of 0.1, 2.5 or 5, and 10 micrograms in order to determine whether the natriuretic action is the result of increased ANF secretion. NPY injection increased significantly IR-ANF while PYY decreased IR-ANF in the dose-response manner in normally-hydrated rats as well as in water-loaded rats. Opposite effects on plasma IR-ANF were exerted by NPY and PYY, indicating that an increase of ANF release may be responsible for NPY-induced natriuresis.