Quantitative Health Risk Assessment of Indoor Radon: A Systematic Review.

Exposure to radon is a well-established cause of lung cancer in the general population. The aim of the present work is to identify and summarize the results of studies that have assessed the risk of lung cancer due to indoor radon, based on a systematic review of relevant published studies. Sixteen studies from 12 different countries met eligibility criteria. Large differences in radon concentrations were noted between and within individual countries, and variety of risk models used to estimate the attributable fraction. Calculating again the attributable fraction in each of these studies using the same model (coefficient of 16% per 100 becquerels per cubic meter (Bq/m3) derived from the European residential radon study), the new attributable fraction of these selected studies ranged from 3% to 17%. Radon remains a public health concern. Information about radon health risks is important and efforts are needed to decrease the associated health problems.

[Knowledge about radon and its associated risk perception in France]. / Connaissance et perception du risque dû au radon en France.

PURPOSE: Radon exposure is a major environmental risk in health. It remains badly known by the general population. It is the second cause of lung cancer, after tobacco smoking. The aim of this cross-sectional general population survey was to describe radon exposure risk knowledge and the socioeconomic factors related to this knowledge. MATERIALS AND METHODS: The Cancer Barometer survey 2010 questioned the French population about its knowledge of radon as such and as health risk factor. This survey was a two-stage random sampling with computer-assisted telephone interview that was performed from April 3, 2010 to August 7, 2010 on a sample of 3,359 people aged 15 to 75 years old. RESULTS: Among people aged 15 to 75 years old, only one in five knows that radon is a natural gas coming from the ground. This knowledge is more frequent among people living in an area that is directly concerned by radon, among men and increases with age, with the level of education and the level of income. Radon risk remains still widely underestimated by the general public, including in areas concerned by this risk. When people were confronted with radon exposure, few intended to remedy by improving their home. CONCLUSION: The success of prevention initiatives implies the support and the collaboration of various national and local actors. To improve their impact for the prevention of lung cancers, it could be more effective to couple these actions with prevention messages on tobacco.

Prevalence, screening and treatment of chronic kidney disease in people with type 2 diabetes in France: the ENTRED surveys (2001 and 2007).

AIMS: The study aimed to assess the prevalence, quality of screening and treatment of chronic kidney disease (CKD), and their trends between 2001 and 2007, in French adults with type 2 diabetes (T2D). METHODS: The 2007 ENTRED survey randomly selected, from French medical insurance fund databases, 8926 adults treated for diabetes who had been reimbursed at least three times over the previous 12 months for oral hypoglycaemic agents or insulin. Medical reimbursement data were extracted and two sets of questionnaires were mailed, one to all patients (48% response rate) and the other to their doctors (62%). Analyses were restricted to the 3894 responders with T2D (2232 with data from their doctors). Trends between the 2001 and 2007 ENTRED surveys were studied. RESULTS: Participants' mean age was 66 years. The prevalence of CKD was estimated to be at least 29%, based on doctors' data (missing data included). Overall, only 17% had no claims for serum creatinine measurements during the year, and 71% had no claims for albuminuria tests; nonetheless, both figures had decreased from 2001. Older people, those who lived alone and those who felt poorly informed about diabetes were more likely to have made no claims for CKD screening. Assessment of quality of care (prescribing antihypertensive treatment when indicated) was possible for 66% of responders, of whom 25% did not receive such treatment. CONCLUSION: CKD is frequently seen in patients with T2D and is likely to be underestimated because albuminuria screening remains inadequate, despite significant improvements since 2001. Further efforts are needed to improve CKD screening, patient and doctor awareness, and adequate use of antihypertensive/nephroprotective medications.

A first national prevalence estimate of diagnosed and undiagnosed diabetes in France in 18- to 74-year-old individuals: the French Nutrition and Health Survey 2006/2007.

AIMS: To estimate the nationwide prevalence of diagnosed and undiagnosed diabetes and pre-diabetes in adults residing in France. METHODS: A probability sample of a non-institutionalized civilian population residing throughout the whole of continental France was recruited from February 2006 to March 2007 for the French Nutrition and Health Survey. All individuals aged between 18 and 74 years who agreed to participate in the survey were included; thus there were 3115 participants, 2102 of whom were undergoing biochemical assessments. The prevalence of diagnosed diabetes was estimated using self-reported diabetes history and the prevalence of undiagnosed diabetes was estimated using fasting plasma glucose ≥ 7.0 mmol/l or HbA(1c) ≥ 6.5% (≥ 48 mmol/mol). RESULTS: The prevalence of diagnosed diabetes was 4.6%, 95% CI 3.6-5.7. The prevalence of undiagnosed diabetes according to standard fasting plasma glucose criteria was 1% (95% CI 0.6-1.7) and contributed to less than 20% of all cases of diabetes. This proportion decreased with age from 30% in 30- to 54-year-olds to 12% in 55- to 74-year-olds. Based on HbA(1c) criteria, the prevalence of undiagnosed diabetes was 0.8% (95% CI 0.4-1.6). CONCLUSIONS: The prevalence of diagnosed diabetes in adults in France is comparable with recent estimates from Northern Europe. The percentage of total diabetes that is undiagnosed is low in France, which may be explained by a widely practised strategy of opportunist screening. During the past years, improvements in diabetes care and increased awareness may have contributed towards decreasing the prevalence of undiagnosed diabetes more widely in Europe, and studies should further monitor such improvements.

Transfer of the shared epitope through microchimerism in women with rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is an autoimmune disease that affects mostly women and is associated with HLA-DRB1 genes having in common a shared epitope sequence. In parallel, cells and/or DNA originating from pregnancy (microchimerism) persist for decades and could contribute to autoimmunity. The aim of this study was to examine whether microchimerism may be a source of the shared epitope among women with RA. METHODS: Women with RA and healthy women who lacked RA-associated genes such as HLA-DRB1*01 (n=33 and n=46, respectively) and/or HLA-DRB1*04 (n=48 and n=64, respectively), were tested for DRB1*01 or DRB1*04 microchimerism by HLA-specific quantitative polymerase chain reaction assays. As controls, alleles not associated with RA (DQB1*02 and DRB1*15/16) were also analyzed. RESULTS: Compared with healthy women, women (42% with RA had a higher frequency and higher levels of DRB1*04 microchimerism versus 8%; P=0.00002) as well as DRB1*01 microchimerism (30% versus 4%; P=0.0015). Moreover, no difference in microchimerism was observed for alleles not associated with RA. CONCLUSION: Women with RA had microchimerism with RA-associated HLA alleles, but not with non-RA-associated HLA alleles, more often and at higher levels compared with healthy women. These observations are the first to indicate that microchimerism can contribute to the risk of an autoimmune disease by providing HLA susceptibility alleles.

HLA-DRB1*0404 is strongly associated with high titers of anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis.

OBJECTIVE: To test whether the presence of RA associated HLA-DRB1*0101, HLA-DRB1*0401 and HLA-DRB1*0404 alleles individually influences anti-cyclic citrullinated peptide antibodies (anti-CCP) production. METHODS: The frequency of anti-CCP antibodies was calculated in the sera of 260 RA patients expressing either two (double dose genotypes SE+/SE+), one (single dose genotypes SE+/SE-) or no RA associated HLA-DR alleles (SE-/SE-). Anti-CCP antibodies titers were also determined. RESULTS: RA associated HLA-DR alleles are not mandatory for production of anti-CCP. We found that 68% of SE-/SE- patients were anti-CCP positive. There was no significant difference in anti-CCP between SE negative patient (SE-/SE-) and patients expressing at least one SE (SE+/SE+ and SE+/SE-) (p=0.140). We observed no statistical difference in anti-CCP between RA patients expressing one or two SE (82% vs. 77%, p=0.577). Among SE+/SE-patients, HLA-DRB1*0404 was associated with anti-CCP with a statistically significant difference compared with SE negative patients (90% anti-CCP positive, p=0.02). HLA-DRB1*0404 was also associated with high titers of anti CCP with a statistically significant difference compared with HLA-DRB1*0401 and HLA-DRB1*0101 patients (p=0.025). CONCLUSIONS: The RA-associated HLA-DRB1*0404 allele was the most strongly associated with the presence of anti-CCP in RA sera. Moreover, HLA-DRB1*0404 patients had higher titers of anti CCP than patients with other RA associated HLA-DR alleles.

HLA-DR polymorphism influences T-cell precursor frequencies to Epstein-Barr virus (EBV) gp110: implications for the association of HLA-DR antigens with rheumatoid arthritis.

To study whether HLA-DR haplotypes associated with susceptibility to develop rheumatoid arthritis (RA) may influence T-cell responses to the Epstein-Barr virus (EBV) gp110 (a protein of the late replicative cycle of EBV), we evaluated the frequency in peripheral blood of T cells capable to proliferate to EBV gp110 by direct limiting dilution analysis in 50 HLA-DR-typed healthy subjects. NVe found that HLA-DRB1*07, an allele associated with reduced risk to develop RA, is associated with the highest frequencies of T cells specific for gp110 in peripheral blood. In contrast, HLA-DRB1*0404, one of the susceptibility alleles is associated with the lowest frequencies of gp110 specific T cells. Finally, people expressing both HLA-DRB1*07 and HLA-DRB1*0404 display low precursor frequencies to EBV gp110.

Adverse cutaneous reactions to trimethoprim-sulfamethoxazole in patients with the acquired immunodeficiency syndrome and Pneumocystis carinii pneumonia.

BACKGROUND AND DESIGN: Patients with the acquired immunodeficiency syndrome are predisposed to cutaneous drug reactions. The reasons are poorly understood and the circumstances in which such patients can be treated through hypersensitivity are a matter of discussion. We assessed the value of clinical and laboratory parameters for predicting trimethoprim-sulfamethoxazole-induced skin reactions and the effects of continued trimethoprim-sulfamethoxazole therapy in such patients. We retrospectively studied all episodes of nonhypoxemic Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome who were treated with trimethoprim-sulfamethoxazole. RESULTS: No clinical or laboratory parameters were found to be predictive of trimethoprim-sulfamethoxazole-induced cutaneous reactions. Of 38 patients treated with trimethoprim-sulfamethoxazole, 18 (47%) developed cutaneous reactions; these occurred within a median of 11 days (range, 7 to 20 days). Of these 18 patients, 12 (67%) continued to be treated with trimethoprim-sulfamethoxazole through hypersensitivity. Trimethoprim-sulfamethoxazole treatment was continued in 19 (95%) of the 20 patients who did not develop cutaneous reactions (P = .067). The mean duration of trimethoprim-sulfamethoxazole therapy was shorter (18 days) in patients who developed skin reactions than in those who did not (20 days) (P = .016). Noncutaneous side effects accounted for all but one interruption of therapy. CONCLUSION: No clinical or laboratory parameters were found to be predictive of cutaneous reactions. By treating through hypersensitivity, 67% of our patients, who otherwise might have had to stop taking trimethoprim-sulfamethoxazole, were able to continue this essential drug therapy.

Effect of corticosteroids on the incidence of adverse cutaneous reactions to trimethoprim-sulfamethoxazole during treatment of AIDS-associated Pneumocystis carinii pneumonia.

We retrospectively studied all courses of treatment with trimethoprim-sulfamethoxazole (TMP-SMZ) alone and with adjuvant corticosteroids for AIDS-associated Pneumocystis carinii pneumonia. The corticosteroids were administered for 8-21 days (mean, 14 days) because of hypoxemia. We evaluated the influence of corticosteroids on the incidence of cutaneous adverse reactions to TMP-SMZ and on the course of AIDS during 3 months of follow-up. Of 38 patients treated with TMP-SMZ alone, 18 (47%) developed cutaneous side effects, whereas three (13%) of the 23 patients who received adjuvant corticosteroid therapy experienced such effects (P = .014). Of the 21 reactive patients, 14 were treated throughout the duration of hypersensitivity. Therapy was interrupted for seven patients (18%) treated with TMP-SMZ alone and for none of those who were given adjuvant corticosteroid therapy (P = .23). During follow-up, the incidence of mucocutaneous herpes simplex virus infection was higher among patients who received adjuvant corticosteroids than among those treated with TMP-SMZ alone (P = .005). Adjuvant corticosteroids thus reduce the incidence of adverse cutaneous reactions to TMP-SMZ in patients with AIDS who are treated for hypoxemic P. carinii pneumonia.

[Cutaneous metastasis disclosing adrenal cortical carcinoma]. / Métastase cutanée révélatrice d'un corticosurrénalome.

Metastases to the skin from internal malignant neoplasms are uncommon and often preterminal event. Cutaneous metastases from an adrenal cortical carcinoma have rarely been reported even in the advanced stages of the disease. A patient was initially seen with a small cutaneous lesion on the cheek and was found to have a large adrenal cortical tumor. Histologic comparison proved that the cutaneous lesion was a metastase from an adrenal cortical carcinoma.

Characterization of translation termination mutations in the spv operon of the Salmonella virulence plasmid pSDL2.

The spv region of the Salmonella virulence plasmids consists of five genes located on an 8-kb fragment previously shown to be essential for virulence in mice. Four structural genes, spvABCD, form an operon that is transcriptionally activated by the spvR gene product in the stationary phase of growth. The role of the individual spv genes in the virulence phenotype was tested by isolating translation termination linker insertions in each gene. Analysis of proteins synthesized in minicells identified each of the spvABCD gene products and confirmed the dependence of spv structural gene expression on the SpvR regulatory protein. The oligonucleotide insertions in spvA, -B, and -C were shown to be nonpolar. Virulence testing indicated that the SpvB protein, regulated by SpvR, is essential for Salmonella dublin to cause lethal disease in mice. Inserts in spvC and spvD were unstable in vivo for unknown reasons, but these mutants still killed mice at slightly higher inocula. Abolition of spvA had no effect on virulence in this system.

Mechanism of resistance to complement-mediated killing of bacteria encoded by the Salmonella typhimurium virulence plasmid gene rck.

We find that pADEO16, a recombinant cosmid carrying the rck gene of the Salmonella typhimurium virulence plasmid, when cloned into either rough or smooth Escherichia coli and Salmonella strains, confers high level resistance to the bactericidal activity of pooled normal human serum. The rck gene encodes a 17-kD outer membrane protein that is homologous to a family of virulence-associated outer membrane proteins, including pagC and Ail. Complement depletion, C3 and C5 binding, and membrane-bound C3 cleavage products are similar in strains with and without rck. Although a large difference in C9 binding was not seen, trypsin cleaved 55.7% of bound 125I-C9 counts from rough S. typhimurium with pADEO16, whereas only 26.4% were released from S. typhimurium with K2011, containing a mutation in rck. The majority of C9 extracted from rck strain membranes sediments at a lower molecular weight than in strains without rck, suggesting less C9 polymerization. Furthermore, SDS-PAGE analysis of gradient peak fractions indicated that the slower sedimenting C9-containing complexes in rck strains did not contain polymerized C9 typical of the tubular membrane attack complex. These results indicate that complement resistance mediated by Rck is associated with a failure to form fully polymerized tubular membrane attack complexes.

Growth regulation of a Salmonella plasmid gene essential for virulence.

The Salmonella dublin plasmid gene vsdC is essential for virulence. We have constructed a vsdC-lacZ translational fusion to demonstrate that vsdC is selectively expressed during the stationary phase of bacterial cell growth. This pattern of expression has been confirmed by mRNA hybridization studies. Carbon starvation is able to induce vsdC expression by limiting bacterial growth. The expression of vsdC is dependent upon an upstream gene, vsdA, whose gene product possesses significant amino-terminus homology with the LysR family of transcriptional activator proteins. We have further demonstrated that vsdC expression is not dependent upon the known Salmonella chromosomal virulence regulatory loci ompR, phoP, and cya-crp and that vsdC can be expressed in a range of nontyphoidal Salmonella serovars, including some serovars in which introduction of the virulence plasmid does not confer mouse virulence. The vsd system provides a model for the study of transcriptional activation, a basis for the development of new expression vectors, and a novel mechanism of virulence gene regulation. Bacterial growth limitation within the phagosomes of host phagocytic cells may be the environmental signal inducing plasmid-mediated virulence gene expression in salmonellae.

A site-specific DNA inversion in Bacteroides plasmid pBF4 is influenced by the presence of the conjugal tetracycline resistance element.

pBF4 is a 42-kb R plasmid from Bacteroides fragilis which transfers clindamycin resistance (Clr) independently of the chromosomal tetracycline resistance (Tcr) transfer element. We have found that this plasmid exists in two nonequimolar conformations, A and B. These forms differ by an inversion of approximately 11.5 kb which does not involve the repeated DNA sequences previously mapped on the plasmid. The presence of chromosomal tetracycline resistance conjugal elements influences the relative amounts of the two conformations: induction with tetracycline shifts the dominant form from B to A.

Molecular analysis of the virulence locus of the Salmonella dublin plasmid pSDL2.

The virulence properties of various non-typhoid Salmonella serotypes depend on the presence of large plasmids 60-100 kb in size. We have shown previously that the virulence region on the 80 kb plasmid pSDL2 of Salmonella dublin Lane maps within a 14kb SalI fragment. In this report we show that an 8.2 kb region within this fragment is sufficient to express lethal disease in BALB/c mice. Sequence analysis of this segment revealed six sequential open reading frames designated vsdA-F, which encode putative proteins of 13-65kDa. Deletion analysis and location of Tn5-oriT inserts which abolish virulence suggest that vsdA, vsdC, vsdD and vsdE are essential for virulence expression. Downstream of vsdF we discovered a locus involved in stable plasmid maintenance. Deletion of that region resulted in plasmid multimerization and instability.

Correlation between the presence of sequences homologous to the vir region of Salmonella dublin plasmid pSDL2 and the virulence of twenty-two Salmonella serotypes in mice.

Large plasmids encoding important virulence properties have been found in several Salmonella serotypes. We have studied the relationship between the presence of a highly conserved 4-kilobase (kb) EcoRI fragment from the plasmid virulence region and pathogenicity for mice of 53 isolates representing 22 serotypes of Salmonella. Only strains possessing the homologous 4-kb region were virulent for mice. In addition, we transferred the virulence plasmid from S. dublin into nine different serotypes, including S. typhi and S. paratyphi A, that lack a native virulence plasmid. Only S. heidelberg and S. newport were rendered mouse virulent by the introduction of the S. dublin plasmid. This study demonstrates that plasmid-mediated virulence sequences are required for Salmonella virulence in mice, but many strains, including the agents of human typhoid fever, also lack chromosomal genes necessary to produce lethal systemic disease in mice. Since all the major Salmonella strains that are host-adapted to animals carry virulence plasmids, it appears that these plasmids are important in mediating systemic infection in animals and may contribute to septicemic, nontyphoid salmonellosis in humans.

Physical and genetic mapping of the Salmonella dublin virulence plasmid pSDL2. Relationship to plasmids from other Salmonella strains.

Plasmids of approximately 80 kb in size are found in nearly all clinical isolates of Salmonella dublin and are believed to be essential for virulence. We have shown previously that the 80-kb plasmid pSDL2 is required for the S. dublin Lane strain to establish a lethal systemic infection in BALB/c mice after oral or intraperitoneal inoculation. We now present a physical and genetic characterization of pSDL2. We have established a complete restriction endonuclease cleavage map of pSDL2 for five enzymes: Xba I, Bam HI, Xho I, Sal I, and Hind III. The region specifying autonomous replication has been localized to a 10.5-kb region of the Sal I A fragment by subcloning on the vector pBR322. Using transposon insertion mutagenesis with Tn5-oriT, a region encoding the virulence phenotype has been mapped within a 6.4-kb portion of the Sal I B fragment. Deletions generated by partial Eco RI restriction digestion demonstrate that at least 50 kb of the plasmid DNA are not required for replication or virulence functions, confirming the map location of these phenotypes. Plasmids of different sizes and restriction patterns were found in mouse virulent strains of S. dublin Vi+, S. enteritidis, and S. choleraesuis. By Southern hybridization, these putative virulence plasmids share a common 4-kb Eco RI fragment with the virulence region of pSDL2, and the plasmids from S. dublin Vi+ and S. enteritidis were shown to express mouse virulence comparable to pSDL2.

Determination of the activity on Legionella of eight macrolides and related agents by comparative testing on three media.

It has proved difficult to develop a standard method for the determination of minimum inhibitory concentrations (MICs) of antibiotics against the Legionellaceae. A major obstacle has been the inactivation of certain antibiotics by components of Charcoal Yeast Extract agar, especially charcoal. To determine the MICs of eight macrolides and related agents (erythromycin, spiramycin, oleandomycin, josamycin, midecamycin, lincomycin, clindamycin and pristinamycin) for 36 strains of Legionella, we used two charcoal-free media: Buffered Yeast Extract agar and Buffered Antibiotic Medium no. 1 (BAM1), the latter having been developed in our own laboratory. The inhibitory effect of charcoal was most marked on josamycin and pristinamycin. This effect was absent on the charcoal-free media, which both, however, inhibited spiramycin. BAM1 agar seemed the better of the two charcoal-free media as it gave more consistent growth. The most active agents were josamycin (0.06-0.25 mg/l), pristinamycin (0.06-0.5 mg/l) and erythromycin (0.12-0.5 mg/l). Midecamycin (0.12-1 mg/l) and spiramycin (1-5 mg/l) also had useful activity.