Early operable breast cancer in elderly women treated with an aromatase inhibitor letrozole as sole therapy

Background:

Primary endocrine therapy (PET) with aromatase inhibitors (AIs) is an option in elderly patients unfit for or unwilling to undergo surgery. We studied the outcome of patients treated with letrozole as PET.

Methods:

Patients with early oestrogen receptor (ER)/progesterone receptor (PR)-positive breast cancer treated with letrozole from February 2001 to September 2009 were reviewed. Inoperable and locally advanced tumours were excluded. Reasons for offering PET, response, survival, cause of death, time to initial and best response, fracture incidence, and late failure rates were studied.

Results:

In all, 104 patients received PET due to frailty (n=48), comorbidity (n=30), old age (n=9), and patient preference (n=17). Median follow-up was 56 months (4–106). Eighty-five cancers responded to letrozole (stable disease (SD, n=19), reduction in size (PR, n=42), and complete response ((CR), n=24)). Median survival was 51 months (4–103), time to initial response (PR/CR) 4.5 months (2–24), and time to best response 8.5 months (3–50). Letrozole was stopped in 25 patients due to progressive disease (n=19), side effects (n=5), and patient choice (n=1). Only 12 of 49 deaths were from breast cancer.

Conclusion:

Letrozole is a reasonable alternative in elderly women with early ER/PR-positive invasive breast cancer who are unfit or unwilling to undergo standard therapy.     

Health and Household Air Pollution from Solid Fuel Use: The Need for Improved Exposure Assessment

Background: Nearly 3 billion people worldwide rely on solid fuel combustion to meet basic household energy needs. The resulting exposure to air pollution causes an estimated 4.5% of the global burden of disease. Large variability and a lack of resources for research and development have resulted in highly uncertain exposure estimates.Objective: We sought to identify research priorities for exposure assessment that will more accurately and precisely define exposure–response relationships of household air pollution necessary to inform future cleaner-burning cookstove dissemination programs.Data Sources: As part of an international workshop in May 2011, an expert group characterized the state of the science and developed recommendations for exposure assessment of household air pollution.Synthesis: The following priority research areas were identified to explain variability and reduce uncertainty of household air pollution exposure measurements: improved characterization of spatial and temporal variability for studies examining both short- and long-term health effects; development and validation of measurement technology and approaches to conduct complex exposure assessments in resource-limited settings with a large range of pollutant concentrations; and development and validation of biomarkers for estimating dose. Addressing these priority research areas, which will inherently require an increased allocation of resources for cookstove research, will lead to better characterization of exposure–response relationships.Conclusions: Although the type and extent of exposure assessment will necessarily depend on the goal and design of the cookstove study, without improved understanding of exposure–response relationships, the level of air pollution reduction necessary to meet the health targets of cookstove interventions will remain uncertain.Citation: Clark ML, Peel JL, Balakrishnan K, Breysse PN, Chillrud SN, Naeher LP, Rodes CE, Vette AF, Balbus JM. 2013. Health and household air pollution from solid fuel use: the need for improved exposure assessment. Environ Health Perspect 121:1120–1128; http://dx.doi.org/10.1289/ehp.1206429     

2-Phenylindole and Arylsulphonamide: Novel Scaffolds Bactericidal against Mycobacterium tuberculosis

相似文献   

Associations between Extreme Precipitation and Gastrointestinal-Related Hospital Admissions in Chennai,India

Background: Understanding the potential links between extreme weather events and human health in India is important in the context of vulnerability and adaptation to climate change. Research exploring such linkages in India is sparse.Objectives: We evaluated the association between extreme precipitation and gastrointestinal (GI) illness-related hospital admissions in Chennai, India, from 2004 to 2007.Methods: Daily hospital admissions were extracted from two government hospitals in Chennai, India, and meteorological data were retrieved from the Chennai International Airport. We evaluated the association between extreme precipitation (≥ 90th percentile) and hospital admissions using generalized additive models. Both single-day and distributed lag models were explored over a 15-day period, controlling for apparent temperature, day of week, and long-term time trends. We used a stratified analysis to explore the association across age and season.Results: Extreme precipitation was consistently associated with GI-related hospital admissions. The cumulative summary of risk ratios estimated for a 15-day period corresponding to an extreme event (relative to no precipitation) was 1.60 (95% CI: 1.29, 1.98) among all ages, 2.72 (95% CI: 1.25, 5.92) among the young (≤ 5 years of age), and 1.62 (95% CI: 0.97, 2.70) among the old (≥ 65 years of age). The association was stronger during the pre-monsoon season (March–May), with a cumulative risk ratio of 6.50 (95% CI: 2.22, 19.04) for all ages combined compared with other seasons.Conclusions: Hospital admissions related to GI illness were positively associated with extreme precipitation in Chennai, India, with positive cumulative risk ratios for a 15-day period following an extreme event in all age groups. Projected changes in precipitation and extreme weather events suggest that climate change will have important implications for human health in India, where health disparities already exist.Citation: Bush KF, O’Neill MS, Li S, Mukherjee B, Hu H, Ghosh S, Balakrishnan K. 2014. Associations between extreme precipitation and gastrointestinal-related hospital admissions in Chennai, India. Environ Health Perspect 122:249–254; http://dx.doi.org/10.1289/ehp.1306807     

Misidentification of English Language Proficiency in Triage: Impact on Satisfaction and Door-to-Room Time

We examined triage nurses’ assessment of patients’ language proficiency compared to patients’ self-reported proficiency and the impact of language discordance on door-to-room time and patient satisfaction. This was a prospective study of emergency department walk-in patients. Patients completed a survey in which they identified their language proficiency. On a Likert scale, patients ranked how well they felt they were understood and how satisfied they were with the triage process. Nurses completed surveys identifying the patient’s primary language and how well they felt they understood the patient. Door-to-room times were obtained from medical records. 163 patients were enrolled. 66 % of patients identified themselves as having good English proficiency, while 34 % of patients had limited English proficiency. Nurses misclassified 27 % of self-identified Spanish-speaking patients as being English proficient. Spanish-speakers felt less satisfied with triage than English-speakers (p < 0.01). There were no differences in door-to-room time. Triage nurses overestimate patient language skills. Spanish-speaking patients feel less satisfied with triage than English-speakers.     

An evaluation of the protective role of α-tocopherol on free radical induced hepatotoxicity and nephrotoxicity due to chromium in rats

Aim:

To avert the health problems induced by many environmental pollutants, available antioxidants have been evaluated. The present study was aimed to investigate whether α-tocopherol could protect the hexavalent chromium (Cr VI)-induced peroxidation in the liver and kidney and to explore the underlying mechanism of the same.

Materials and Methods:

A total of 24 Wistar adult female rats were equally divided into four groups. Group 1 served as control while Groups 2 and 3 were administered K₂Cr₂O₇(10 mg/kg b.wt. s.c. single dose). In addition to (Cr VI), Group 3 also received α-tocopherol (125 mg/kg, daily) by oral gavage for 14 days. Group 4 was maintained as α-tocopherol control (dose as above). At the end of 14 days, blood samples were drawn for hematology. Subsequently, all the rats were sacrificed to collect liver and kidney samples for assay of tissue peroxidation markers, antioxidant markers and functional markers and histopathology.

Results:

Administration of chromium (Cr VI) in Group 2 significantly (P < 0.05) reduced the antioxidant markers such as superoxide dismutase and reduced glutathione along with significant (P < 0.05) increase in peroxidation markers such as malondialdehyde and protein carbonyls in the liver and kidney as compared with other groups. The functional markers in serum such as total protein was decreased significantly (P < 0.05), whereas other functional markers viz. alanine transaminase, blood urea nitrogen and creatinine were increased significantly (P < 0.05) in Group 2 as compared with the other groups. Significant (P < 0.05) decrease in hemoglobin, packed cell volume, total erythrocyte count, mean corpuscular volume, mean corpuscular hemoglobin and total leukocyte count were observed in Cr VI treated Group 2 rats. Prominent pathological changes were observed in the liver and kidney of Group 2. Co-treatment with α-tocopherol in Group 3 rats significantly (P < 0.05) reversed the Cr VI induced changes. The parameters in the study in Group 4 did not differ as compared with Group 1.

Conclusions:

α–tocopherol exhibited protective effect against Cr VI-induced damage to the liver and kidney by inhibition of lipid peroxidation owing its antioxidant activity.KEY WORDS: α-tocopherol, chromium (Cr VI), kidney, lipid peroxidation, liver     

Effect of dietary protein, dichlorodiphenyltrichloroethane (DDT) and hexachlorocyclohexane (HCH) on hepatic microsomal enzyme activity in rats

1. Albino rats were fed on diets containing 30, 120 or 200 g protein/kg with or without the incorporation of dichlorodiphenyltrichloroethane (DDT) or hexachlorocyclohexane (HCH) at 100 mg/kg diet for 4 weeks. 2. The activities of the liver microsomal enzymes NADPH-cytochrome reductase (EC 1.6.2.4), flavoprotein-linked monooxygenase (EC 1.14.14.1) and O-demethylase were significantly greater in animals fed on 120 and 200 g protein/kg diet compared with those fed on 30 g protein/kg diet. 3. The inclusion of DDT or HCH at all protein intakes led to further significant rises in microsomal enzyme activities but the increases were much greater for animals receiving the 120 and 200 g protein/kg diets than for those receiving the 30 g protein/kg diet. 4. The results imply that detoxification of DDT or HCH was carried out more effectively at the higher protein intakes.     

A Comparative Study on Surgical Outcomes of Glued Intraocular Lens and Sutured Scleral Fixated Intraocular Lens Implantation

Purpose: To compare the surgical outcomes of glued intraocular lens (GIOL) and sutured scleral fixated intraocular lens (SFIOL) implantation. Methods: A retrospective, interventional case series of 60 patients (68 eyes) who underwent GIOL (28 eyes: 11 primary; 17 secondary) and SFIOL (40 eyes: 24 primary; 16 secondary) in a tertiary eye care institute was done. The main outcome measures were complications, time taken for surgery, postoperative refractive outcomes, and final best-corrected visual acuity (BCVA). Results: The mean final BCVA was 0.42 (20/40) (+/– SD 0.29) in the GIOL group and 0.57 (20/50) (+/– SD 0.48) in the SFIOL group (p=0.08). The time taken for primary GIOL (mean+/– SD: 66+/–19 minutes) was significantly lower than primary SFIOL (means+/–SD: 94+/–34 minutes) (p=0.006). The complications were comparable between the GIOL (25%) and SFIOL (15%) groups (p=0.30). The most common complication noted was transient vitreous hemorrhage (GIOL 17%, SFIOL 5%). The only sight-threatening complication seen was retinal detachment, with one eye in each group. The mean follow-up was 20 (GIOL) and 20.4 weeks (SFIOL). Conclusion: Both glued intraocular lens and sutured scleral fixated intraocular lens are safe and effective procedures in cases of insufficient capsular support. In view of the shorter surgical time with similar outcomes, primary GIOL can be considered as a preferred surgical option over primary SFIOL.     

Allele and genotype frequency of CYP2C9 in Tamilnadu population

Objectives To identify the frequency of CYP2C9*1, *2 and *3 alleles and the genotype of CYP2C9 gene in the Tamilian population.Methods The study was conducted on 135 unrelated healthy human volunteers. DNA was extracted from the peripheral leukocytes samples and was analyzed using the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) protocol. The PCR products were digested with AvaII, KpnI or NsiI restriction enzymes. The digested products were separated using 8% polyacrylamide gel and stained by ethidium bromide. Genotyping of the subjects was done based on DNA fragment size.Results The frequencies of CYP2C9*1, *2 and *3 alleles in the Tamilian population were 0.907, 0.026 and 0.067, respectively. The distribution of CYP2C9*1/*1, *1/*2, *1/*3 and *2/*3 genotypes were 0.823, 0.044, 0.126 and 0.007, respectively.Conclusion CYP2C9*3 is the most frequent mutant allele found in the Tamilian population. The distribution of this mutant allele in the Tamilian population was found to be lesser than in Caucasians but higher than in Chinese.