Breast cancer screening beliefs by practice location

Background

This study examines variations in breast cancer screening among primary care clinicians by geographic location of clinical practice.

Methods

A cross-sectional survey design was used to examine approaches to breast cancer screening among physicians, nurse practitioners, and physician assistants involved in primary care practice. A summary index of beliefs about breast cancer screening was created by summing the total number of responses in agreement with each of four survey items; values for this summary variable ranged between zero and four. Respondents were classified into urban, rural and suburban categories based upon practise location.

Results

Among the 428 respondents, agreement with "correct" responses ranged from 50% to 71% for the individual survey items; overall, half agreed with three or more of the four breast cancer screening items. While no significant differences were noted by practice location, variation in responses were evident. Reported use of written breast cancer guidelines was less in both suburban (OR = 0.51) and urban areas (OR = 0.56) when compared to clinicians in rural areas.

Conclusion

Development of an evidence-based consensus statement regarding breast cancer screening would support a single set of unambiguous guidelines for implementation in all primary care settings, thus decreasing variations in how breast cancer screening is approached across varied clinical settings.

     

Metabolic activation of methyl-hydroxylated derivatives of 7,12- dimethylbenz[a]anthracene by human liver dehydroepiandrosterone-steroid sulfotransferase

Methyl-hydroxylated metabolites of the potent carcinogen, 7,12- dimethylbenz[a]anthracene (DMBA), namely, 7-hydroxymethyl-12- methylbenz[a]anthracene (7-OH-DMBA), 7-methyl-12- hydroxymethylbenz[a]anthracene (12-OH-DMBA) and 7,12- dihydroxymethylbenz[a]anthracene (7,12-diOH-DMBA), were examined as substrates for sulfotransferase bioactivation in different human tissue cytosols. Hepatic cytosols, which were able to catalyze the 3'- phosphoadenosine 5'-phosphosulfate (PAPS)-dependent DNA binding of 7-OH- DMBA, 12-OH-DMBA and 7,12-diOH-DMBA, were highly sensitive to inhibition by dehydroepiandrosterone (DHEA), a specific substrate for human DHEA-steroid sulfotransferase (IC50 = 5 microM). By comparison, 2,6-dichloro-4-nitrophenol, a potent inhibitor of the thermostable (TS)- phenol and estrogen sulfotransferases, did not have an appreciable inhibitory effect. Neither p-nitrophenol, a high affinity substrate for human TS-phenol and estrogen sulfotransferases, nor dopamine, a specific substrate for the thermolabile (TL)-phenol sulfotransferase, significantly inhibited the DNA binding of 12-OH-DMBA catalyzed by hepatic cytosols. Inter-subject variation (n = 12) of the PAPS- dependent DNA binding of 12-OH- and 7,12-diOH-DMBAs also correlated well with DHEA-sulfotransferase activity (r = 0.90; P < 0.00001 and r = 0.92; P < 0.00001, respectively). This sulfation-dependent metabolic activation was not detected in cytosols from human colon, pancreas, larynx or mammary gland. Both TS- and TL-phenol sulfotransferases were active in human liver and colon but only liver contained DHEA- sulfotransferase activity. These results indicate that the sulfotransferase-mediated activation of the methyl-hydroxylated DMBAs is predominantly catalyzed by DHEA-steroid sulfotransferase in human liver and that TS- and TL-phenol sulfotransferases and estrogen sulfotransferase are not involved in the catalysis.      

Methotrexate reduces inflammatory cell numbers, expression of monokines and of adhesion molecules in synovial tissue of patients with rheumatoid arthritis

Methotrexate (MTX) is one of the most widely prescribed drugs in the treatment of rheumatoid arthritis (RA). The mechanism by which MTX exerts its anti-rheumatic effect has not yet been defined. The aim of the present study was to investigate the effect of MTX treatment (7.5- 15 mg/week) on synovial tissue in RA. For this purpose, synovial biopsies were taken from 11 RA patients before and 16 weeks after initiation of MTX therapy. Immunohistochemistry was performed using monoclonal antibodies (MAb) specific for CD3, CD4, CD8, CD22, CD25, CD38, CD68, MAb67, Ki67, interferon gamma (IFN-gamma), interleukin (IL)- 1alpha, IL-1beta, tumour necrosis factor alpha (TNF-alpha), E-selectin, ICAM-1 and VCAM-1. All parameters for disease activity improved during the period of treatment. Immunohistochemical analysis revealed a statistically significant decrease in scores for CD3, CD8, CD38, CD68, Ki67, IL-1beta, TNF-alpha and the adhesion molecules E-selectin and VCAM-1. The observed decrease in synovial scores for inflammatory cells, monokines and adhesion molecules suggests that the anti- inflammatory effect of MTX is, in part, dependent on a reduction in monokine-inducible vascular adhesion molecules and subsequent reduction of cell traffic into joints.      

Human CD4 lymphocytes specifically recognize a peptide representing the fusion region of the hybrid protein pml/RAR alpha present in acute promyelocytic leukemia cells

Fusion proteins present in leukemic cells frequently contain a new amino acid at the fusion point. We tested whether a peptide (BCR1/25) encompassing the fusion region of the hybrid molecule pml/RAR alpha, which is selectively expressed by acute promyelocytic leukemia (APL) cells, can be recognized by human T lymphocytes in vitro. CD4+ lymphocytes, at both polyclonal and clonal level, recognized peptide BCR1/25 in an HLA-DR--restricted fashion on presentation by autologous antigen-presenting cell (APC) or by APC expressing the HLA-DR11 restricting molecule. Control peptides corresponding to the normal pml and RAR alpha proteins were not recognized. One clone (DEG5) also exerted a high and specific cytotoxicity against autologous cells pulsed with BCR1/25. The autologous DE LCL containing a transduced pml/RAR alpha fusion gene and expressing a bcr1 type of the pml/RAR alpha hybrid protein induced the proliferation of DE anti-BCR1/25 T cell clones. It is concluded that the bcr1 type-pml/RAR alpha fusion protein of APL contains an antigenic site, absent from the normal parent molecules and recognized by human CD4+ lymphocytes.     

The American Digestive Health Foundation: Advancing digestive health through support of research and education in the cause, prevention, treatment, and cure of digestive diseases

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Prospective identification of HEV-B enteroviruses during the 2005 outbreak

Enteroviruses (EVs) represent the main etiological agents of epidemics of viral meningitis and especially the serotypes related to the human enterovirus B species. Genetic typing by sequencing a PCR-amplified portion of the genome has proved to be useful for identifying EVs and is more rapid than standard seroneutralization tests. However, prospective genotyping has not been reported in routine practice within a clinical diagnostic laboratory. A genetic typing assay using two sets of primers was developed for the amplification and sequencing of the VP1 coding sequence of the HEV-B serotypes. Identification was carried out by sequence comparisons with EV sequences in GenBank using the BLAST search tool and confirmed by phylogenetic analysis. This method was used to identify prospectively the 48 enteroviruses isolated in patients with either enterovirus-proved meningitis (n = 41) or other clinical manifestations (n = 7) admitted to the University Hospital of Clermont-Ferrand (France) in 2005. The assay was also used to type retrospectively EVs isolated in cerebrospinal fluid specimens of 25 patients admitted to the Trousseau Paediatric Hospital in Paris (France) between February and August 2005. In both prospective and retrospective investigations of meningitis, echovirus 30 (E30) was the most frequent serotype, followed in decreasing order by E18, E13, coxsackievirus B5, B3, E6, E4, E7, E11, E33, and coxsackievirus A9. In patients with other manifestations, coxsackievirus B3, B5, and E3 were each identified twice, and E2 once. In E30 infected patients, nine different lineages were demonstrated by phylogenetic analysis. Genetic typing allowed the prospective, effective and rapid identification of all EV isolates involved in the 2005 outbreak. Molecular typing in combination with phylogenetic analysis will be a reliable means to confirm the emergence of new EV variants, and is of interest of both individual patients and public health.