PAHs and PM2.5 emissions and female breast cancer incidence in metro Atlanta and rural Georgia

Environmental chemical exposure could be an important etiologic factor for geographic differences in breast cancer incidence. In this study, we examined emissions of polycyclic aromatic hydrocarbons (PAHs) and PM_2.5 in relation to breast cancer incidence in metro Atlanta and rural Georgia by analyzing data from the Surveillance, Epidemiology, and End Results Program and the Environmental Protection Agency. The results showed that metro Atlanta had a significantly higher age-adjusted annual incidence rate of female breast cancer than rural Georgia (132.6 vs. 113.7 per 100,000) for 1992–2011. Emissions of both PAHs [adjusted β = 0.568 (95 % CI: 0.209, 0.927); p = 0.004] and PM_2.5 [adjusted β = 2.964 (95 % CI: 0.468, 5.459); p = 0.023] were significantly associated with breast cancer incidence in metro Atlanta area. This study suggests that ambient air pollution, especially PAHs and PM_2.5, could have a significant impact on the increased incidence of female breast cancer in urban areas.     

Contraceptive efficacy of the Copper T380A and the Multiload Cu250 IUD in three developing countries

The clinical performance of the Copper T380A (TCu380A) and the Multiload 250 (MLCu250) intrauterine devices (IUDs) were evaluated for 12 months in a group of women who had one of the two IUDs inserted. Results are from a randomized clinical trial conducted at four collaborating research sites located in three developing countries.The gross cumulative life-table pregnancy rate of the TCu380A IUD was significantly lower than the rate with the MLCu250 IUD at 12 months (0.5 and 1.2, respectively,p<0.01). No statistically significant differences between the two study IUDs were found with regard to IUD expulsion or IUD removal due to bleeding/pain, personal reasons, medical reasons, or planned pregnancy. TCu380A IUD users were more likely to report experiencing increased dysmenorrhea (p<0.01) or intermenstrual pelvic pain (p<0.01) than were MLCu250 IUD users. However, few of these users discontinued use of their assigned IUD because of having experienced menstrual bleeding disturbances or intermenstrual pelvic pain.These data indicate that the TCu380A IUD may be a better option than the MLCu250 IUD for women wishing to practice highly effective long-term birth control without having to resort to hormonal methods.

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Resumen El resultado clínico de los dispositivos intrauterinos (DIU) Copper T380A y Multiload 250 (MLCu250) se evaluó durante 12 meses en un grupo de mujeres a quienes se había colocado uno de los dos DIU. Los resultados corresponden a un ensayo clínico aleatorizado efectuado en cuatro emplazamientos de investigaciones en colaboración situados en tres países en desarrollo.La tasa bruta acumulativa de embarazo de las tablas de vida del DIU TCu380A fue significativamente inferior a la tasa correspondiente al DIU MLCu250 a los 12 meses (0,5 y 1,2, respectivamente,p<0,01)). No hubo diferencias estadísticamente significativas entre los dos DIU del estudio con respecto a su expulsión o retiro debido a microrragia/dolor, razones personales, razones médicas o embarazo planificado. Era más probable que las usuarias del DIU TCu380A notificaran mayor dismenorrea (p<0,01) o dolor pélvico intermenstrual (p<0,01) que las usuarias del DIU MLCu250. Sin embargo, un número menor de este grupo de usuarias dejó de utilizar el DIU que le había sido asignado por haber experimentado trastornos menstruales de microrragia o dolor pélvico intermenstrual.Estos datos indican que el DIU TCu380A podría ser una mejor opción que el DIU MLCu250 para las mujeres que desean praticar un control de la natalidad a largo plaza altamente eficaz sin tener que recurrir a métodos hormonales.

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Resumé Les résultats cliniques des dispositifs intra-utériens (DIU) Copper T38OA (TCu380A) et Multiload 250 (MLCu250) ont été évalués pendant 12 mois chez un groupe de femmes qui portaient l'un ou l'autre de ces dispositifs. Les résultats proviennent d'un essai clinique randomisé, effectué en collaboration par quatre établissements de recherche dans trois pays en développement.Au terme de 12 mois, le taux brut cumulé de grossesses des tables de survie pour le dispositif TCu380A était significativement inférieur au taux correspondant pour le dispositif MLCu250 (0,5 et 1,2 respectivement,p<0,01). Aucune différence statistiquement significative entre les deux dispositifs étudiés n'a été constatée du point de vue de l'expulsion du DIU ou de son retrait pour cause de microrragie/douleurs, pour des raisons personnelles ou médicales ou pour une grossesse planifiée. Les utilisatrices du TCu380A ont plus fréquemment signalé une dysménorrhée (p<0,01) ou des douleurs pelviennes intermenstruelles (p<0,01) que les utilisatrices du MLCu250. Peu nombreuses était cependant cells qui avaient, en raison de perturbations du flux menstruel ou de douleurs pelviennes intermenstruelles, abandonné l'usage du dispositif qui leur avait été assigné.Ces résultats indiquent que le dispositif TCu380A représente peut-être une meilleure solution que le dispositif MLCu250 pour les femmes recherchant à long terme une méthode hautement efficace de régulation des naissances, sans avoir recours aux méthodes hormonales.

     

Association of TNF-beta polymorphism with disease severity among patients infected with hepatitis C virus

The pathogenesis of chronic hepatitis C virus (HCV) infection remains unclear. Tumour necrosis factor alpha (TNF-alpha) is alleged to contribute in the pathogenesis of chronic HCV infection. Single nucleotide polymorphism in TNF-alpha and -beta genes could influence the outcome of HCV infection. The aim was to study single nucleotide polymorphism in TNF-alpha promoter region and Nco I polymorphisms in the TNF-beta gene in patients with chronic hepatitis C. Fifty-two patients with histologically proven chronic hepatitis, who had raised ALT levels (>1.5 x ULN) and were HCV RNA positive, were studied. Genotyping of -308 promoter variant of TNF-alpha was performed by PCR with primers that incorporated an Nco I restriction site. For PCR typing of the TNF-beta Nco I restriction fragment length polymorphism, sequence specific primers were used. Polymorphism in the TNF-alpha G/G, G/A and A/A allele was not different between HCV patients and healthy controls. TNF-beta A/A allele was significantly more common (P = 0.02) in patients (28.8%) as compared to controls (12.8%), whereas no significant difference was observed for TNF-beta G/A and G/G alleles [corrected]. Nco I TNF-beta A/A was strongly associated with -308 TNF-alpha G/G (RR of HCV persistence = 4.9), indicating possible linkage between TNF-beta A/A and TNF-alpha G/G allele. Patients with severe hepatic fibrosis more frequently had the TNF-beta A/A allele as compared to patients with mild disease (P = 0.04). Immunogenetic factors, such as single nucleotide polymorphisms in TNF-beta (A/A allele), may affect the natural course of HCV infection, in particular, the disease progression. Larger studies including cytokine expression profiles are needed to fully understand the contribution of the polymorphisms described in the pathogenesis of chronic hepatitis C.     

Inactivation of the p16 gene by hypermethylation and loss of heterozygosity in adenocarcinoma of the lung

We investigated the aberrant promoter hypermethylation of p16, p15 and p14 genes and loss of heterozygosity (LOH) at 9p21-22 in 48 cases of adenocarcinoma of the lung. The frequencies of hypermethylation of genes were as follows: p16, 25.0%; p15, 22.9%; and p14, 18.8%. The frequency of LOH at chromosome 9p21-22 was 60.9%. The frequency of two-hit inactivation of the p16 gene by hypermethylation and LOH was 21.7%. Two-hit inactivation of the p16 gene showed loss of protein expression and was significantly correlated with tumor size, tumor grade and the Ki-67 labeling index. Hypermethylation of the p16 gene was not significantly correlated with hypermethylation of the p15 and p14 genes, both of which are close to the p16 gene locus, suggesting that hypermethylation of these genes occurs selectivity. In conclusion, biallelic inactivation of the p16 gene by hypermethylation and LOH might cause loss of p16 expression and play an important role in the development of adenocarcinoma of the lung. Therefore, controlling and monitoring for hypermethylation of the p16 gene may be partially useful for treatment and early diagnosis of adenocarcinoma of the lung.     

Improved therapeutic responses in a xenograft model of human B lymphoma (Namalwa) for liposomal vincristine versus liposomal doxorubicin targeted via anti-CD19 IgG2a or Fab' fragments.

PURPOSE: Monoclonal antibody-mediated targeting of liposomal anticancer drugs to surface antigens expressed on malignant B cells can be an effective strategy for treating B-cell malignancies. In a murine model of human B-cell lymphoma, we have made in vitro and in vivo comparisons of long-circulating sterically stabilized (Stealth) immunoliposome (SIL) formulations of two anticancer drugs, vincristine (VCR) and doxorubicin (DXR), with different mechanisms of action and drug release rates. EXPERIMENTAL DESIGN: SIL formulations of VCR or DXR were conjugated to the monoclonal antibody anti-CD19 (SIL[alphaCD19]) or its Fab' fragments (SIL[Fab']). Specific binding of SILs to Namalwa cells was studied using radiolabeled liposomes, and cytotoxicities of DXR- or VCR-loaded SILs were quantitated by a tetrazolium assay. Pharmacokinetic and drug leakage experiments were performed in mice using dual-labeled liposomes, and the therapeutic responses of SILs were evaluated in a Namalwa (human B lymphoma) cell xenograft model. RESULTS: SIL[alphaCD19] or SIL[Fab'] had higher association with and cytotoxicity against Namalwa cells than nontargeted liposomes. SIL[Fab'] had longer circulation times than SIL[alphaCD19], and VCR had faster release rates from the liposomes than DXR. SIL formulations of either VCR or DXR had significantly better therapeutic outcomes than nontargeted liposomes or free drugs. SILs loaded with VCR were superior to those loaded with DXR. SIL[Fab'] had better therapeutic outcomes than SIL[alphaCD19] for the drug DXR but were equally efficacious for the drug VCR. CONCLUSIONS: Treatment of a B lymphoma model with single injections of anti-CD19-targeted liposomal formulations of VCR resulted in high levels of response and long-term survivors. Responses to anti-CD19-targeted liposomal DXR were more modest, although the longer circulation times of SIL[Fab'] versus SIL[alphaCD19] led to superior therapeutics for DXR-loaded immunoliposomes.     

Bedside ultrasound as a predictive tool for acute chest syndrome in sickle cell patients

Background

Acute chest syndrome (ACS) is the leading cause of death for patients with sickle cell disease (SCD). Early recognition of ACS improves prognosis.