Breast cancer screening utilization by Latina community health center clients

Studies have demonstrated the importance of cost constraintsand cultural differences on the receipt of health services.Characteristics of health services delivery systems have alsobeen shown to influence the use of services by the poor. Thisstudy reports on the status of breast cancer screening experienceand factors associated with utilization in women clients ofan urban community health center. The clients were predominantlyof Latina origin, had an eighth-grade education or less andreported an income of $5000 or less. Nevertheless, 75% had hada clinical breast exam (CBE) in the past year and 59% had everhad a mammogram. However, few women had received regular screeningby mammography. In addition to physician recommendation anddiscussion with a doctor or nurse, previous breast problemsand the belief that most women over 50 get mammograms were associatedwith ever having had a mammogram. Insurance and entitlementcoverage was very important to mammography experience. Findingsreinforce the importance of investigating delivery system factorswhen assessing utilization and underscore the important roleproviders play in initiating discussion of screening needs andencouraging regular screening.     

Genetic alterations in combined neuroendocrine neoplasms of the lung.

Large-cell neuroendocrine and small-cell lung carcinomas are highly aggressive neuroendocrine tumors that can be associated in a variant of 'small-cell lung carcinoma combined with large-cell neuroendocrine carcinoma'. Little is known about this rare tumor type with biphenotypic neuroendocrine differentiation. The aim of the present study was to genetically characterize each component of a series of combined small-cell/large-cell neuroendocrine carcinomas, to gain information on their histogenesis and to compare the alterations observed with those found in their respective pure forms. To this end, 22 formalin-fixed, paraffin-embedded lung neuroendocrine tumors obtained from surgical resections were investigated: six combined small-cell/large-cell carcinomas, eight pure large-cell carcinomas and eight pure small-cell carcinomas. For the combined neuroendocrine neoplasms, DNA was extracted separately from each of the two cytologically different populations. Allelic imbalance was investigated by PCR amplification of 30 highly polymorphic microsatellite markers located at 11 different chromosomal regions. A common background of genetic alterations, similar in both components of the combined neoplasms, was demonstrated at 17p13.1, 3p14.2-3p21.2, 4q12-4q24, 5q21 and 9p21. In fact, the two components appeared to be more similar to each other than to their respective pure forms. In addition, allelic imbalances preferentially involving one of the two components were found. These alterations often appeared to be specific for this histological variant, as compared with those observed in pure forms or in the literature. In conclusion, this is the first report in which a molecular characterization of the variant of small-cell lung carcinoma combined with large-cell neuroendocrine carcinoma was performed. The finding of common alterations in the two phenotypically different neuroendocrine cell components suggests a close genetic relationship and supports the hypothesis of a monoclonal origin from a common ancestor. The genetic differences observed provide the basis for the divergent differentiation and parallel the morphological differences in the two components of these combined neuroendocrine neoplasms.     

The effectiveness of using standardized patients to improve community physician skills in mammography counseling and clinical breast exam.

BACKGROUND: Traditional didactic continuing education is relatively ineffective in improving physicians' clinical skills. We hypothesized that a centralized course including small group workshops utilizing standardized patients could improve clinical skills for a reasonable cost. METHODS: We designed a 5-h course aimed at improving physicians' counseling skills (re: screening mammography) and clinical breast exam (CBE) skills. The course included lectures, demonstrations, and small group skills sessions utilizing standardized patients and was offered to 156 typical community-based primary care physicians. Pre- and postcourse evaluation included in-office assessments of physician CBE and counseling performance by standardized patients and a written test of knowledge and attitudes. RESULTS: A total of 54.5% of eligible physicians participated. They improved modestly in only one of three areas of counseling skills measured (providing counseling appropriate to the patient's readiness to accept mammography, P = 0.01). The overall CBE score increased substantially from 24.8 to 34.7 (P < 0.0001). Knowledge in all areas measured and confidence in counseling patients also increased. The basic course cost $202 per physician trained. CONCLUSIONS: Most community-based primary care physicians may find small group training and in-office evaluation involving standardized patients acceptable. Such training may be more effective in improving physical exam skills than complex communication skills.     

Rapid detection of Flt3 mutations in acute myeloid leukemia patients by denaturing HPLC

BACKGROUND: fms-related tyrosine kinase 3 (Flt3) is the most commonly mutated gene in human acute myeloid leukemia (AML) and has been implicated in its pathogenesis. Because screening of Flt3 in AML patients by PCR followed by gel electrophoresis is time-consuming and fails to detect some very small internal tandem duplications (ITDs), we developed a method for screening of FLT3 receptor mutations with PCR plus denaturing HPLC (D-HPLC). METHODS: Total mRNAs extracted from 34 AML patients were first analyzed for the presence of juxtamembrane length mutations and tyrosine kinase domain point mutations by a conventional method involving PCR amplification, restriction enzyme digestion, and agarose gel electrophoresis (PCR-RED-AGE). Subsequently, the same patient panel was analyzed by D-HPLC, using specifically designed primers and optimized running temperatures for the length and point mutation analysis. RESULTS: Thirty-four patients were analyzed by PCR-RED-AGE; 9 were positive for known Flt3 mutations: 6 of 34 (18%) for ITDs in exon 14 and 3 of 34 (9%) for point mutations in exon 20. The same patient panel was analyzed by D-HPLC, and additional nucleotide changes were discovered; in total, 14 sequence variations were identified: 7 of 34 (21%) for ITDs in exon 14; 2 of 34 (6%) for point mutations in exon 20; 1 of 34 (3%) for a new point mutation in exon 16; and 4 of 34 (12%) for polymorphisms in exons 13 and 14. Direct sequencing analysis identified nucleotide alterations in each of the "D-HPLC positives" but in none of the "D-HPLC negatives", yielding a specificity and sensitivity of 100% for D-HPLC-based screening. CONCLUSIONS: This novel D-HPLC-based procedure, which is optimized for identification of new point mutations in the catalytic and regulatory domains of FLT3 receptor, could potentially be useful for studies involving precise genotype determination, which could be critical for selection of innovative AML therapies targeting the FLT3 protein.     

Minimal‐power control of hydrogen evolution reactions

An integral approach to solve finite‐horizon optimal control problems posed by set‐point changes in electrochemical hydrogen reactions is developed. The methodology extends to nonlinear problems with regular, convex Hamiltonians that cannot be explicitly minimized, i.e. where the functional dependence of the H‐minimal control on the state and costate variables is not known. The Lagrangian functions determining trajectory costs will not have special restrictions other than positiveness, but for simplicity the final penalty will be assumed quadratic. The answer to the problem is constructed through the solution to a coupled system of three first‐order quasi‐linear partial differential equations (PDEs) for the missing boundary conditions x(T), λ(0) of the Hamiltonian equations, and for the final value of the control variable u(T). The independent variables of these PDEs are the time‐duration T of the process and the characteristic parameter S of the final penalty. The solution provides information on the whole (T, S)‐family of control problems, which can be used not only to construct the individual optimal control strategies online, but also for global design purposes. Copyright © 2009 John Wiley & Sons, Ltd.     

Helping men make an informed decision about prostate cancer screening: A pilot study of telephone counseling

Objective

Evaluate a computer-assisted telephone counseling (CATC) decision aid for men considering a prostate specific antigen (PSA) test.

Methods

Eligible men were invited by their primary care providers (PCPs) to participate. Those consenting received an educational booklet followed by CATC. The counselor assessed stage of readiness, reviewed booklet information, corrected knowledge deficits and helped with a values clarification exercise. The materials presented advantages and disadvantages of being screened and did not advocate for testing or for not testing. Outcome measures included changes in stage, decisional conflict, decisional satisfaction, perceived vulnerability and congruence of a PSA testing decision with a pros/cons score. Baseline and final surveys were administered by telephone.

Results

There was an increase in PSA knowledge (p < 0.001), and in decisional satisfaction (p < 0.001), a decrease in decisional conflict (p < 0.001), and a general consistency of those decisions with the man's values. Among those initially who had not made a decision, 83.1% made a decision by final survey with decisions equally for or against screening.

Conclusions

The intervention provides realistic, unbiased and effective decision support for men facing a difficult and confusing decision.

Practice implications

Our intervention could potentially replace a discussion of PSA testing with the PCP for most men.     

Histamine regulates autoreactive T cell activation and adhesiveness in inflamed brain microcirculation

Histamine may contribute to the pathology of MS and its animal model EAE. We explored the effects of histamine and specific HR agonists on activation and migratory capacity of myelin-autoreactive T cells. We show that histamine in vitro inhibits proliferation and IFN-γ production of mouse T cells activated against PLP(139-151). These effects were mimicked by the H1R agonist HTMT and the H2R agonist dimaprit and were associated with reduced activation of ERK½ kinase and with increased levels of cell cycle inhibitor p27Kip-1, both involved in T cell proliferation and anergy. H1R and H2R agonists reduced spontaneous and chemokine-induced adhesion of autoreactive T cells to ICAM-1 in vitro and blocked firm adhesion of these cells in inflamed brain microcirculation in vivo. Thus histamine, through H1R and H2R, inhibits activation of myelin-autoreactive T cells and their ability to traffic through the inflamed BBB. Strategies aimed at interfering with the histamine axis might have relevance in the therapy of autoimmune disease of the CNS.