Determinants of tissue estradiol levels and biologic responsiveness in breast tumors

Estradiol stimulates the growth of breast tumor cells in both pre- and post menopausal women. Following the menopause, the levels of estradiol in breast tumor tissues are similar to those from tumors obtained prior to cessation of ovarian function, even though plasma estrogen levels are 10–50 fold lower in post- than in premenopausal women. These observations suggested the possibility of enhanced estradiol uptake from plasma or in situ synthesis in post-menopausal women. We systematically studied these possibilities in a series of model systems. Initially we demonstrated a very high affinity estradiol binding site in tissues from castrated rats. Enhanced uptake occurred under conditions of low plasma estrogen levels when compared to animals with higher estradiol levels. In situ synthesis also occurred both through the sulfatase and aromatase pathways. In further studies, we compared uptake from plasma with in situ synthesis via aromatase in a nude mouse model. Under the conditions utilized, in situ synthesis resulted in much higher tissue estradiol levels and tumor growth rates than did uptake from plasma. During these studies we demonstrated that tumors deprived of estradiol developed mechanisms rendering them more sensitive to estrogen. This involved the ability of cells to adapt to estradiol deprivation to allow them to be responsive to four log lower amounts of estrogen than when studied under wild type conditions. In addition, cells adapted by increasing their level of aromatase and thus developing the capability to become more sensitive to estrogen precursors. Taken together, these studies demonstrate that breast cancer tissue is highly plastic and can adapt to conditions of estrogen deprivation via a variety of mechanisms.     

Diffuse panbronchiolitis: Case report and review of the literature

Diffuse panbronchiolitis is an uncommon disease of unknown aetiology mainly occurring in Asian races. Treatment with erythromycin acting through unclarif ied mechanisms is promising and may improve the poor prognosis currently associated with the disease. A case is presented illustrating how the imaging features of the disease, particularly on high-resolution computed tomography, may be used to support a diagnosis suggested on clinical grounds.     

Smoking practices in New York City: The use of a population-based survey to guide policy-making and programming

To inform New York City’s (NYC’s) tobacco control program, we identified the neighborhoods with the highest smoking rates, estimated the burden of second-band smoke exposure, assessed the early response to state taxation, and examined cessation practices. We used a stratified random design to conduct a digit-dialed telephone survey in 2002 among 9,674 New York City adults. Our main outcome measures included prevalence of cigarette smoking, exposure to second-hand smoke, the response of smokers to state tax increases, and cessation practices. Even after controlling for sociodemographic factors (age, racelethnicity, income, education, marital status, employment status, and foreign-born status) smoking rates were highest in Central Harlem and in the South Bronx. Sixteen percent of nonsmokers reported frequent exposure to second-hand smoke at home or in a workplace. Among smokers with a child with asthma, only 33% reported having a no-smoking policy in their homes. More than one fifth of smokers reported reducing the number of cigarettes they smoked in response to the state tax increase. Of current smokers who tried to quit, 65% used no cessation aid. These data were used to inform New York City’s smoke-free legislation, taxation, public education, and a free nicotine patch give-away program. In conclusion, large, local surveys can provide essential data to effectively advocate for, plan, implement, and evaluate a comprehensive tobacco control program. Dr. Mostashari (the guarantor) made substantial contributions to the conception, design, and supervision of this paper, the analysis and interpretation of data, the drafting of the paper, critical revisions of the paper for important intellectual content, and the acquisition of data and funding for this research. Dr. Kerker made substantial contributions to the analysis and interpretation of data, the drafting of the paper and critical revisions of the paper for important intellectual content. Ms. Hajat made substantial contributions to the acquisition of data and critical revisions of the paper for important intellectual content. Dr. Miller made substantial contributions to the conception of this paper and critical revisions of the paper for important intellectual content. Dr. Frieden made substantial contributions to the conception, design, and supervision of this paper and critical revisions of the paper for important intellectual content.     

Male Rape,Some Notes on the Laboratory Investigation

The incidence of sexual assault continues to escalate, and it is under-reported. Recent literature discusses the medical, legal, and psychological management of the female sexual assault victim, but little has been written regarding appropriate management of male sexual assault. This article focuses on the laboratory investigation in male rape case.     

The Effects of the Going Places Program on Early Adolescent Substance Use and Antisocial Behavior

This study evaluated the effects of a school-based intervention on growth trajectories of smoking, drinking, and antisocial behavior among early adolescents. Seven middle schools were randomized to intervention or comparison conditions and students in two successive cohorts (n = 1484) provided five waves of data from sixth to ninth grade. The Going Places Program, included classroom curricula, parent education, and school environment components. Latent growth curve analyses demonstrated significant treatment group effects, including reducing increases in friends who smoke, outcome expectations for smoking, and smoking progression, but had non-significant effects on drinking or antisocial behavior. The Going Places Program was effective in preventing increases in smoking progression, but its efficacy as a more cross-cutting problem behavior preventive intervention was not confirmed.     

Comparison of internal radiation doses estimated by MIRD and voxel techniques for a "family" of phantoms

The aim of this study was to use a new system of realistic voxel phantoms, based on computed tomography scanning of humans, to assess its ability to specify the internal dosimetry of selected human examples in comparison with the well-established MIRD system of mathematical anthropomorphic phantoms. Differences in specific absorbed fractions between the two systems were inferred by using organ dose estimates as the end point for comparison. A "family" of voxel phantoms, comprising an 8-week-old baby, a 7-year-old child and a 38-year-old adult, was used and a close match to these was made by interpolating between organ doses estimated for pairs of the series of six MIRD phantoms. Using both systems, doses were calculated for up to 22 organs for four radiopharmaceuticals with widely differing biodistribution and emission characteristics (technetium-99m pertechnetate, administered without thyroid blocking; iodine-123 iodide; indium-111 antimyosin; oxygen-15 water). Organ dose estimates under the MIRD system were derived using the software MIRDOSE 3, which incorporates specific absorbed fraction (SAF) values for the MIRD phantom series. The voxel system uses software based on the same dose calculation formula in conjunction with SAF values determined by Monte Carlo analysis at the GSF of the three voxel phantoms. Effective doses were also compared. Substantial differences in organ weights were observed between the two systems, 18% differing by more than a factor of 2. Out of a total of 238 organ dose comparisons, 5% differed by more than a factor of 2 between the systems; these included some doses to walls of the GI tract, a significant result in relation to their high tissue weighting factors. Some of the largest differences in dose were associated with organs of lower significance in terms of radiosensitivity (e.g. thymus). In this small series, voxel organ doses tended to exceed MIRD values, on average, and a 10% difference was significant when all 238 organ doses were considered as a single group. In 12 comparisons of effective dose, the mean voxel to MIRD ratio was 1.07 (range 0.72-1.32). It was shown for the majority of cases that, whereas some large differences in SAF values exist, differences in source organ and effective dose values between the MIRD and voxel methods were largely accounted for by the respective organ mass differences. The reasons for various organ dose differences with the selected radiopharmaceuticals are discussed. Taking biological variation into account, there is reasonable agreement between the two methods but some significant differences exist that warrant further investigation. More extensive comparisons involving a wide variety of voxel phantoms are required to establish whether realistic voxel phantoms should eventually replace the MIRD system.     

Genetic screening,health care and the insurance industry

The potential use of genetic tests in insurance has raised concerns about discrimination and individuals losing access to health care either because of refusals to test for treatable diseases, or because test-positives cannot afford premiums. Governments have so far largely sought to restrict the use of genetic information by insurance companies. To date the number of tests available with significant actuarial value is limited. However, this is likely to change, raising more clearly the question as to whether the social costs of adverse selection outweigh the social costs of individuals not accessing health care for fear of the consequences of test information being used in insurance markets. In this contribution we set out the policy context and model the potential trade-offs between the losses faced by insurers from adverse selection by insurees (which will increase premiums reducing consumer welfare) and the detrimental health effects that may result from persons refusing to undergo tests that could identify treatable health conditions. It argues that the optimal public policy on genetic testing should reflect overall societal benefit, taking account of these trade-offs. Based on our model, the factors that influence the outcome include: the size of and value attached to the health gains from treatment; deterrent effects of a disclosure requirement on testing for health reasons; incidence of the disease; propensity of test-positives to adverse select; policy value adverse selectors buy in a non-disclosure environment; and price elasticity of demand for insurance. Our illustrative model can be used as a benchmark for developing other scenarios or incorporating real data in order to address the impact of different policies on disclosure and requirement to test.     

Arginine: mediator or modulator of sepsis?

Arginine is a conditionally essential amino acid that plays pivotal roles in maintaining body homeostasis. Arginine is a substrate for protein synthesis but can also be metabolized to various bioactive compounds that include nitric oxide, ornithine, polyamines, creatine phosphate, agmatine, and dimethylarginines. Arginine produces physiologic effects via nitric oxide dependent and independent pathways. Nitric oxide is important for the modulation of vascular tone, inflammation, immune function, endothelial function, platelet and leukocyte adherence, and neurotransmission. Nitric oxide modulates many biochemical processes important for the response to sepsis. Arginine, independent of nitric oxide, is important for growth, wound healing, cardiovascular function, immune function, inflammatory responses, energy metabolism, urea cycle function, and other metabolic processes. Arginine supplementation improves outcomes in animals with sepsis, wounds, ischemia-reperfusion injury, and following thermal injury. Enteral administration of arginine improves endothelial function but has little effect upon hemodynamics during human sepsis. An analysis of clinical studies using enteral formulas with supplemental arginine suggests benefits upon outcome, with no evidence of significant detrimental effects.     

National Performance Measures for Diabetes Mellitus Care

When considering the trends in disease management, the focus of healthcare in the US has shifted from communicable diseases, which can most often be managed successfully, to chronic diseases, which are currently not managed very well. Chronic diseases, such as diabetes mellitus, become a lifelong health problem for the individual, the family, and in the workplace. Currently, there is no vaccine to prevent diabetes and no cure for diabetes once acquired. In order to improve the quality of care for diabetes, national performance measures have been developed to provide a unified set of diabetes-specific performance and outcome measures.The Diabetes Quality Improvement Project (DQIP) founded in 1997 through a partnership between the Center for Medicare and Medicaid Services, the National Committee for Quality Assurance, and the American Diabetes Association, established a single, standardized set of performance measures for diabetes care quality improvement and accountability in the US, which were published in 1998. The DQIP measures are noteworthy as a model for many other chronic diseases. Indeed, the DQIP represents the first widely adopted comprehensive performance measurement standards, not just for diabetes but for any single chronic disease. This is of further significance since it was developed by a coalition of public and private entities in the US.In order to prevent long-term complications from diabetes, there needs to be a physician-coordinated treatment plan involving a team approach to the problem. When such a physician-coordinated treatment plan is developed in conformance with the comprehensive performance measures, the prospects for a greater impact on diabetes might be enhanced.Overall, national performance measures for diabetes care have been widely adopted into health plan quality initiatives and have resulted in increased efforts to promote preventative screening and testing. Better compliance has lead to more stringent glucose control and helped to educate the public on the utility of the glycosylated hemoglobin level test for finding those at risk for microvascular and neuropathic complications. While more Americans with diabetes are receiving the recommended standards of care as a result of the implementation of national performance measures, diabetes management remains suboptimal but achievable.The authors concluded from this review that national performance measures have provided health plans and providers with objective tools to measure quality; however, these measures now need to move to prevention standards and initiatives. Policy development for diabetes care must continue to move from managing chronic illness to preventative screening of pre-diabetes through to identification and modification of lifestyle risk factors.