Vaccination coverage reinforced by an infectious disease consultation during pretransplant check-up in patients awaiting kidney transplantation: A randomized study.

BACKGROUND: Vaccine coverage (VC) in patients awaiting kidney transplantation is insufficient. METHODS: We performed a prospective, single-center, interventional, randomized, open-label study comparing a reinforced group (infectious disease consultation proposed) and a standard group (letter stating vaccine recommendations sent to the nephrologist) of patients in our institution awaiting renal transplantation. FINDINGS: Out of the 58 eligible patients, 19 declined to participate. Twenty patients were randomized to the standard group and 19 to the reinforced group. Essential VC increased from. 10% to 20% in the standard group and from 15.8% to 52.6% in the reinforced group (p < 0.034). The main obstacles identified were lack of vaccination traceability, refusal of an additional consultation and the journey time between home and hospital. CONCLUSION: While introduction of an infectious disease consultation during the pre-transplant check-up significantly improved VC in patients, it is time-consuming and failed to achieve a satisfactory rate of VC.

Prevalence of aortic valve dystrophy and insufficiency in a cohort of 255 HIV-positive patients followed-up in a cardiology department between 2012 and 2014.

OBJECTIVES: To study valve appearance and the presence of valve disease in a cohort of people living with HIV (PLHIV). DESIGN: A prospective study of PLHIV examined at the cardiology department of the Clermont Ferrand university hospital group (CHU) between January 1, 2012, and December 31, 2014. Were excluded those with a history of infection associated with a possible endocarditis. METHODS: Demographic, medical characteristics and cardiovascular disease risk factors at time of cardiovascular examination and Doppler-echocardiography were recorded and analyzed. RESULTS: In total, 903 PLHIV were examined in the infectious diseases department, 255 of whom were included. These consisted of 67 women (26.3%) and 188 men, of a mean age of 51.2±9.7years, in whom coronary artery disease was diagnosed in 18 patients (7.0%), two women and 16 men, representing a prevalence of 3.0% in females and 8.5% in males. The appearance of the aortic cusps was considered dystrophic in 14.1% of cases (36/255), dysplastic in two cases (0.8%), exhibiting a bicuspid deformity in one case. The prevalence of aortic valve abnormality was therefore 6.0% in the women (4/67) and 17.0% in the men (32/188). On facing off this data with the Kora Monica study findings, an increase in prevalence appears only to truly manifest after 50years of age. We registered 35 aortic insufficiency cases (13.7%), representing a higher incidence than that of the Framingham cohort, with age and masculine gender being the determining factors. CONCLUSION: Valve disease, along with coronary artery disease, should be closely monitored in PLHIV.

The features of infectious diseases departments and anti-infective practices in France and Turkey: a cross-sectional study.

The aim of this study was to assess the infectious diseases (ID) wards of tertiary hospitals in France and Turkey for technical capacity, infection control, characteristics of patients, infections, infecting organisms, and therapeutic approaches. This cross-sectional study was carried out on a single day on one of the weekdays of June 17-21, 2013. Overall, 36 ID departments from Turkey (n = 21) and France (n = 15) were involved. On the study day, 273 patients were hospitalized in Turkish and 324 patients were followed in French ID departments. The numbers of patients and beds in the hospitals, and presence of an intensive care unit (ICU) room in the ID ward was not different in both France and Turkey. Bed occupancy in the ID ward, single rooms, and negative pressure rooms were significantly higher in France. The presence of a laboratory inside the ID ward was more common in Turkish ID wards. The configuration of infection control committees, and their qualifications and surveillance types were quite similar in both countries. Although differences existed based on epidemiology, the distribution of infections were uniform on both sides. In Turkey, anti-Gram-positive agents, carbapenems, and tigecycline, and in France, cephalosporins, penicillins, aminoglycosides, and metronidazole were more frequently preferred. Enteric Gram-negatives and hepatitis B and C were more frequent in Turkey, while human immunodeficiency virus (HIV) and streptococci were more common in France (p < 0.05 for all significances). Various differences and similarities existed in France and Turkey in the ID wards. However, the current scene is that ID are managed with high standards in both countries.

Shift of the 2009-2011 measles outbreak from children to adults: an observational review at the University Hospital of Clermont-Ferrand, France.

In 2009-2011, 113 adult in- and outpatients with measles were referred to the University Hospital of Clermont-Ferrand (centre of France): 71 (62.8 %) needed hospitalisation, 31 had pneumonia, 29 diarrhoea, 47 liver enzymes elevation, 38 thrombopaenia, one encephalitis and there were no deaths. Nineteen cases occurred among healthcare workers and five of them were hospital-acquired. There were 92 unvaccinated patients. The 2011 peak of that measles re-emerging epidemic occurred when non-immunised adults were affected.

[Prognostic value of the LRINEC score (Laboratory Risk Indicator for Necrotizing Fasciitis) in soft tissue infections: a prospective study at Clermont-Ferrand University hospital]. / Valeur pronostique du score Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) dans les dermohypodermites infectieuses : étude prospective au CHU de Clermont-Ferrand.

BACKGROUND: The LRINEC score was developed in a retrospective study in order to distinguish necrotizing fasciitis from severe soft tissue infections using laboratory data. AIM: To evaluate the prognostic value of the LRINEC score in infectious cellulitis. PATIENTS AND METHODS: A prospective study was performed at the departments of infectious diseases and dermatology of the Clermont-Ferrand University Hospital. The three evaluation criteria were: time from initiation of antibiotics to regression of erythema, duration of fever and occurrence of complications (abscess, surgery, septic shock, necrotizing fasciitis, death, transfer to intensive care). Potential predictive variables were: LRINEC score>6 at admission, comorbidities, local appearance, clinical presentation and soft tissue ultrasound results. RESULTS: Fifty patients were included. The rate of complications was higher for patients with a LRINEC score>6 (54%) than for patients with a score<6 (12%, P=0.008). However, a LRINEC score>6 on admission was not significantly associated with increased duration of erythema or of fever. Prior lymphoedema was associated with a better prognosis. DISCUSSION: The LRINEC score may be a useful tool for the detection of complicated forms of soft tissue infections. Patients with a LRINEC score>6 on admission should be carefully evaluated (hospitalization, surgical assessment, close monitoring).

[Carcinoma cuniculatum: an uneasy diagnosis to suspect in case of chronic osteomyelitis with unsuccessful outcome despite appropriate antibiotic therapy]. / Carcinome cuniculatum: un diagnostic difficile, à évoquer devant une ostéite chronique d'évolution défavorable sous traitement.

INTRODUCTION: The clinical and histological features of cuniculatum carcinoma (CC) are often misleading. CASE REPORT: We report a case of CC of the foot, which was misdiagnosed as osteomyelitis for a two year period and which relapsed 2 months after complete resection. DISCUSSION: The CC has to be evoked in patients with chronic osteomyelitis and torpid wound. The anatomopathologist needs to be aware of the suspected diagnosis.

[Infections associated to severe thrombotic events and antiphospholipid antibodies]. / Infections associées à des évènements thrombotiques sévères avec présence d'anticorps antiphospholipides.

The authors present 2 cases of infections in which the presence of antiphospholipid antibodies (APL), anticardiolipin and anti-beta2-GP1, was associated to the occurrence of significant thrombotic events: 1) a 55-year-old male patient whose serology (indirect immunofluorescence) revealed Coxiella burnetii infection (phase 2 antigens) with IgG at 1,600 and IgM at 50 (significant titer: IgG>or=200 and IgM>or=50); 2) and a 20-year-old male patient with a CMV infection confirmed by serology (IgG: 44 U/ml, significant threshold 6, IgM: 2.1 U/ml, significant threshold 0.9).

A widespread and early requirement for a novel Notch function during Drosophila embryogenesis.

The Notch pathway plays a key role in the formation of many tissues and cell types in Metazoans. We recently showed that Notch acts in two pathways to determine muscle precursor fates. The first is the "standard" Notch pathway, in which Delta activates the Notch receptor, which then translocates into the nucleus in conjunction with Su(H) to reprogram transcription patterns and bring about changes in cell fates. The second pathway is poorly defined, but known to be independent of the ligands and downstream effectors of the standard pathway. The standard pathway is required in many different developmental contexts and we wondered if there was also a general requirement for the novel pathway. Here we show that the novel Notch pathway is required for the development of each of five examined cell types. These results indicate that the novel pathway is a widespread and fundamental component of Notch function. We further show that both Notch pathways operate in the differentiation of the same cell types. In such cases, the novel pathway acts first and appears to set up or limit the size of equivalence groups. The standard pathway then acts within the equivalence groups to limit individual cell fates.

The pore-forming and cytoplasmic domains of the neurogenic gene product, BIG BRAIN, are conserved between Drosophila virilis and Drosophila melanogaster.

The Drosophila BIG BRAIN (BIB) protein functions critically in the determination of neuroblasts in the embryonic ectoderm and many other cell types. BIB is a member of the MIP family of transmembrane channel proteins. The conserved channel domain of BIB is flanked by amino- and carboxy-terminal cytoplasmic domains of unique sequence, which comprise over two-thirds of the protein. To determine whether the cytoplasmic domains of BIB are important for BIB function, we have cloned and sequenced the bib gene of D. virilis and compared it with that of D. melanogaster. Here we report that the channel domain and both cytoplasmic domains are highly conserved between the two species. The conservation of the cytoplasmic domains indicates that they are critical to BIB function. bib transcripts are found in similar patterns in both species, indicating that the developmental function(s) of BIB have also been conserved.

Evidence for a novel Notch pathway required for muscle precursor selection in Drosophila.

The Notch pathway mediates cell fate choice in many species and developmental contexts. In the Drosophila mesoderm, phenotypic differences were observed when different components of the pathway were defective. To determine if these differences reflect variations in the signaling pathway or in the persistence of wild-type maternal products, we examined muscle precursors in embryos that lacked both maternally- and zygotically-derived gene products, called holonull embryos. Most holonull neurogenic embryos have the same number and arrangement of extra muscle precursors, but in Notch holonull embryos many additional cells also become muscle precursors. Thus Notch is active in cells where its known ligands and downstream effectors are not. These results indicate that Notch acts in two pathways to determine cell fates in mesoderm: the Delta-to-Notch-to-Suppressor of Hairless-to-Enhancer of split signaling pathway previously defined, and a second pathway that acts independently.

Antineurogenic phenotypes induced by truncated Notch proteins indicate a role in signal transduction and may point to a novel function for Notch in nuclei.

Loss of any one of several neurogenic genes of Drosophila results in overproduction of embryonic neuroblasts at the expense of epidermoblasts. In this paper a variety of altered Notch proteins are expressed in transgenic flies. Dominant lethal, antineurogenic phenotypes were produced by expression of three classes of mutant proteins: (1) a protein comprised of the cytoplasmic domain of Notch and devoid of sequences permitting membrane association; (2) a transmembrane protein lacking the extracellular, lin12/Notch repeats; and (3) transmembrane proteins carrying amino acid substitutions replacing one or both extracellular cysteines thought to be involved in Notch dimerization. These Notch proteins not only suppress the neural hypertrophy observed in Notch- embryos, but also generate a phenotype in which elements of the embryonic nervous system are underproduced. Action of the intracellular cdc10 repeats appears to be essential for wild-type Notch function or for the antineurogenic activity of these proteins. The activities of the dominant, gain-of-function proteins indicate that Notch functions as a signal transducing receptor during ectoderm development. Production of antineurogenic Notch proteins in embryos deficient for the other neurogenic genes allowed functional dependencies to be established. Delta, mastermind, bigbrain, and neuralized appear to function in elaboration of a signal upstream of Notch. Genes of the Enhancer of split complex act after Notch. The cytoplasmic domain of Notch contains nuclear localization sequences that function in cultured cells, and one of the Notch antineurogenic proteins, the cytoplasmic domain, accumulates in nuclei in vivo.

A role for the Drosophila neurogenic genes in mesoderm differentiation.

The neurogenic genes of Drosophila have long been known to regulate cell fate decisions in the developing ectoderm. In this paper we show that these genes also control mesoderm development. Embryonic cells that express the muscle-specific gene nautilus are overproduced in each of seven neurogenic mutants (Notch, Delta, Enhancer of split, big brain, mastermind, neuralized, and almondex), at the apparent expense of neighboring, nonexpressing mesodermal cells. The mesodermal defect does not appear to be a simple consequence of associated neural hypertrophy, suggesting that the neurogenic genes may function similarly and independently in establishing cell fates in both ectoderm and mesoderm. Altered patterns of beta 3-tubulin and myosin heavy chain gene expression in the mutants indicate a role for the neurogenic genes in development of most visceral and somatic muscles. We propose that the signal produced by the neurogenic genes is a general one, effective in both ectoderm and mesoderm.

Molecular control of the induction of alcohol dehydrogenase by ethanol in Drosophila melanogaster larvae.

The activity of alcohol dehydrogenase (ADH:EC 1.1.1.1), the initial enzyme in the major pathway for ethanol degradation, is induced in Drosophila melanogaster larvae by low concentrations of dietary ethanol. Two lines of evidence indicate that the metabolic products of the ADH pathway for ethanol degradation are not directly involved in the induction of Adh. First, the accumulation of the proximal transcript in Adhn2 larvae was increased when the intracellular level of ethanol was elevated. In addition, the ADH activity, the proximal Adh mRNA, and the intracellular concentration of ethanol were elevated coordinately in wild-type larvae fed hexadeuterated-ethanol, which is metabolized more slowly than normal ethanol. An examination of P element transformant lines with specific deletions in the 5' regulatory DNA of the Adh gene showed that a DNA sequence between +527 and +604 of the distal transcript start site is essential for the induction of the Adh gene [corrected]. The DNA sequence between -660 and about -5000 of the distal transcript start site was important for the down-regulation of the induction response.

Identification of cis-regulatory elements required for larval expression of the Drosophila melanogaster alcohol dehydrogenase gene.

The Alcohol dehydrogenase (Adh) genes of two distantly related species, Drosophila melanogaster and Drosophila mulleri, display similar, but not identical, patterns of tissue-specific expression in larvae and adults. The regulatory DNA sequences necessary for wild-type Adh expression in D. mulleri larvae were previously reported. In this paper we present an analysis of the DNA sequences necessary for wild-type Adh expression in D. melanogaster larvae. We show that transcription from the proximal promoter of the melanogaster Adh gene is regulated by a far upstream enhancer and two or more elements near the transcription start site. The enhancer is tissue specific and stimulates transcription to high levels in fat body and to lower levels in midgut and malpighian tubules whether linked to the proximal promoter or to a heterologous promoter. The enhancer activity localized to at least two discrete regions dispersed over more than 1.7 kb of DNA. Deletion of any one of these subregions reduces Adh transcription in all three larval tissues. Similarly, two regions immediately upstream of the proximal promoter start site are necessary for wild-type transcription levels in all three tissues. Thus, each of the identified regulatory elements is sufficient for low levels of Adh gene expression in all three larval tissues, but maximal levels of expression requires the entire set.

The role of specific enhancer-promoter interactions in the Drosophila Adh promoter switch.

The Drosophila melanogaster alcohol dehydrogenase (Adh) gene is transcribed from two promoters active at different developmental stages. In this paper we show that the promoters are differentially stimulated by two enhancers, the Adh larval enhancer and the Adh adult enhancer. In early larval stages, the larval enhancer stimulates transcription from the proximal promoter; in late larval stages, the two enhancers act synergistically to stimulate transcription from the distal promoter; and in adults, the adult enhancer stimulates transcription from the distal promoter. To determine the basis for these enhancer-promoter interactions, we examined the effect of each enhancer on three different promoters. We found that the adult enhancer is stage specific and stimulates transcription from all three promoters. In contrast, the larval enhancer is potentially active in all stages and stimulates transcription from only two of the three promoters. These observations suggest that normal temporal expression of Adh depends on the stage-specific activity of the adult enhancer and the differential response of the proximal and distal promoters to the larval enhancer.

Role of transcriptional interference in the Drosophila melanogaster Adh promoter switch.

The Drosophilia melanogaster alcohol dehydrogenase (Adh) gene is transcribed from two closely linked promoters, which are regulated by two upstream enhancers. The proximal promoter is active primarily in first to early third-instar larvae, whereas the distal promoter is active in late third-instar larvae and adults. The Adh larval enhancer and the proximal promoter are separated by the Adh adult enhancer and the distal promoter. Because the proximal promoter is turned off just as the distal promoter is turned on, we considered the possibility that the distal promoter or adult enhancer has a role in the downregulation of the proximal promoter. We report here that transcription from the distal promoter is required to shut off the proximal promoter. In the absence of the distal promoter, the proximal promoter is active throughout larval development and in adults. The proximal promoter is also aberrantly active in adults when placed upstream of the distal promoter. These results suggest that the developmental switch from proximal to distal promoter is regulated by the stage-specific activation of the distal promoter, and the subsequent repression of the proximal promoter by transcriptional interference.

High-level expression of a cloned HLA heavy chain gene introduced into mouse cells on a bovine papillomavirus vector.

A gene encoding the heavy chain of an HLA human histocompatibility antigen was isolated from a library of human DNA by recombination and selection in vivo. After insertion into a bovine papillomavirus (BPV) DNA expression vector, the gene was introduced into cultured mouse cells. Cells transformed with the HLA-BPV plasmids did not appear to contain extrachromosomal viral DNA, whereas BPV recombinants usually replicated as plasmids in transformed cell lines. Large amounts of HLA RNA were produced by the transformed cells, and the rate of synthesis of human heavy chain was several-fold higher than in the JY cell line, a well-characterized human lymphoblastoid cell line which expresses high levels of surface HLA antigen. Substantial amounts of human heavy chain accumulated in the transformed cells, and HLA antigen was present at the cell surface. These observations establish the feasibility of using BPV vectors to study the structure and function of HLA antigens and the expression of cloned HLA genes.

Nucleotide sequence of the 3' half of AKV.

We report the nucleotide sequence of the 3' half of the ecotropic murine leukemia virus AKV genome. To obtain a preliminary sequence, we developed a sequencing strategy whereby a nested set of restriction fragments is chemically modified prior to gel purification and strand scission. The sequence defines the genetic map of the 3' half of AKV and locates recombinant regions previously identified in structural analyses of MCF viruses.