Publications

Using a real-time PCR assay specific for a mosaic penA allele that has been associated with oral cephalosporin resistance in Asia, 54 available Neisseria gonorrhoeae isolates collected in San Francisco, CA, from January to October 2008 were analyzed. Five isolates tested positive for the mosaic penA gene by real-time PCR. DNA sequencing revealed two mosaic penA alleles (SF-A and SF-B). Isolates with SF-A and SF-B alleles possessed elevated MICs for the oral cephalosporins cefpodoxime and cefixime.

BACKGROUND

Failing to inform a patient of an abnormal outpatient test result can be a serious error, but little is known about the frequency of such errors or the processes for managing results that may reduce errors.

METHODS

We conducted a retrospective medical record review of 5434 randomly selected patients aged 50 to 69 years in 19 community-based and 4 academic medical center primary care practices. Primary care practice physicians were surveyed about their processes for managing test results, and individual physicians were notified of apparent failures to inform and asked whether they had informed the patient. Blinded reviewers calculated a "process score" ranging from 0 to 5 for each practice using survey responses.

RESULTS

The rate of apparent failures to inform or to document informing the patient was 7.1% (135 failures divided by 1889 abnormal results), with a range of 0% to 26.2%. The mean process score was 3.8 (range, 0.9-5.0). In mixed-effects logistic regression, higher process scores were associated with lower failure rates (odds ratio, 0.68; P < .001). Use of a "partial electronic medical record" (paper-based progress notes and electronic test results or vice versa) was associated with higher failure rates compared with not having an electronic medical record (odds ratio, 1.92; P = .03) or with having an electronic medical record that included both progress notes and test results (odds ratio, 2.37; P = .007).

CONCLUSIONS

Failures to inform patients or to document informing patients of abnormal outpatient test results are common; use of simple processes for managing results is associated with lower failure rates.

AIMS

Atrial natriuretic peptide (ANP) is a hormone that has both antihypertrophic and antifibrotic properties in the heart. We hypothesized that myocyte-derived ANP inhibits endothelin (ET) gene expression in fibroblasts.

METHODS AND RESULTS

We have investigated the mechanism(s) involved in the antiproliferative effect of ANP on cardiac fibroblasts in a cell culture model. We found that cardiac myocytes inhibited DNA synthesis in co-cultured cardiac fibroblasts as did treatment with the ET-1 antagonist BQ610. The effect of co-culture was reversed by antibody directed against ANP or the ANP receptor antagonist HS-142-1. ANP inhibited the expression of the ET-1 gene and ET-1 gene promoter activity in cultured fibroblasts. The site of the inhibition was localized to a GATA-binding site positioned between -132 and -135 upstream from the transcription start site. GATA4 expression was demonstrated in cardiac fibroblasts, GATA4 bound the ET-1 promoter both in vitro and in vivo, and siRNA-mediated knockdown of GATA4 inhibited ET-1 expression. ET-1 treatment resulted in increased levels of phospho-serine(105) GATA4 in cardiac fibroblasts and this induction was partially suppressed by co-treatment with ANP.

CONCLUSION

Collectively, these findings suggest that locally produced ET-1 serves as an autocrine stimulator of fibroblast proliferation, that ANP produced in neighbouring myocytes serves as a paracrine inhibitor of this proliferation, and that the latter effect operates through a reduction in GATA4 phosphorylation and coincident reduction in GATA4-dependent transcriptional activity.

PURPOSE

This is the first study describing the tobacco industry's objectives developing and publishing lifestyle magazines, linking them to tobacco marketing strategies, and how these magazines may encourage smoking.

METHODS

Analysis of previously secret tobacco industry documents and content analysis of 31 lifestyle magazines to understand the motives behind producing these magazines and the role they played in tobacco marketing strategies.

RESULTS

Philip Morris (PM) debuted Unlimited in 1996 to nearly 2 million readers and RJ Reynolds (RJR) debuted CML in 1999, targeting young adults with their interests. Both magazines were developed as the tobacco companies faced increased advertising restrictions. Unlimited contained few images of smoking, but frequently featured elements of the Marlboro brand identity in both advertising and article content. CML featured more smoking imagery and fewer Camel brand identity elements.

CONCLUSIONS

Lifestyle promotions that lack images of smoking may still promote tobacco use through brand imagery. The tobacco industry still uses the "under-the-radar" strategies used in development of lifestyle magazines in branded Websites. Prohibiting lifestyle advertising including print and electronic media that associate tobacco with recreation, action, pleasures, and risky behaviors or that reinforces tobacco brand identity may be an effective strategy to curb young adult smoking.

An HIV-seropositive man who presented with cough, low-grade fever and difficulty in breathing was admitted to the pulmonology unit at Mulago Hospital in Kampala, Uganda. He was initially diagnosed with bacterial pneumonia and treated with ceftriaxone without significant improvement. Induced sputum and bronchoalveolar lavage specimens were collected and stained using a modified Giemsa stain (Diff-Quik). With this technique, it was possible to demonstrate cystic and trophic forms of Pneumocystis jirovecii and confirm the diagnosis of Pneumocystis pneumonia in this patient.

Several functional and structural imaging studies have investigated the neural basis of personality in healthy adults, but human lesions studies are scarce. Personality changes are a common symptom in patients with neurodegenerative diseases like frontotemporal dementia (FTD) and semantic dementia (SD), allowing a unique window into the neural basis of personality. In this study, we used the Interpersonal Adjective Scales to investigate the structural basis of eight interpersonal traits (dominance, arrogance, coldness, introversion, submissiveness, ingenuousness, warmth, and extraversion) in 257 subjects: 214 patients with neurodegenerative diseases such as FTD, SD, progressive nonfluent aphasia, Alzheimer's disease, amnestic mild cognitive impairment, corticobasal degeneration, and progressive supranuclear palsy and 43 healthy elderly people. Measures of interpersonal traits were correlated with regional atrophy pattern using voxel-based morphometry (VBM) analysis of structural MR images. Interpersonal traits mapped onto distinct brain regions depending on the degree to which they involved agency and affiliation. Interpersonal traits high in agency related to left dorsolateral prefrontal and left lateral frontopolar regions, whereas interpersonal traits high in affiliation related to right ventromedial prefrontal and right anteromedial temporal regions. Consistent with the existing literature on neural networks underlying social cognition, these results indicate that brain regions related to externally focused, executive control-related processes underlie agentic interpersonal traits such as dominance, whereas brain regions related to internally focused, emotion- and reward-related processes underlie affiliative interpersonal traits such as warmth. In addition, these findings indicate that interpersonal traits are subserved by complex neural networks rather than discrete anatomic areas.

PURPOSE

Raloxifene reduces vertebral fracture and invasive breast cancer risks, but increases fatal strokes in postmenopausal women at increased coronary risk. We assessed whether this risk is concentrated in postmenopausal women already at high stroke risk.

METHODS

Raloxifene Use for The Heart (RUTH) enrolled 10,101 postmenopausal women (mean age 67 years) with or at increased coronary heart disease risk; Multiple Outcomes of Raloxifene Evaluation (MORE) enrolled 7705 osteoporotic postmenopausal women (mean age 66 years). A Framingham Stroke Risk Score (FSRS) was calculated for all women with no prior cerebrovascular events (n = 16,858). The validity of the FSRS was assessed in the placebo groups, and then raloxifene-associated stroke risk was analyzed by FSRS subgroups.

RESULTS

FSRS predicted an increased stroke risk in the placebo group of both clinical trials. There was no difference in the incidence of nonfatal strokes between the raloxifene and placebo groups in MORE or RUTH, regardless of baseline Framingham stroke risk. In RUTH, women with FSRS <13 showed no increase in raloxifene-associated fatal stroke risk (hazard ratio [HR] 1.08; 95% confidence interval [CI], 0.49-2.37). Those with FSRS >or=13 had a 75% increased risk of raloxifene-associated fatal stroke (HR 1.75; 95% CI, 1.01-3.02; interaction P = .33). In MORE, where 80% of women had a FSRS <13, no increase in fatal (HR 0.57; 95% CI, 0.19-1.68) stroke risk was observed.

DISCUSSION

Risk of fatal stroke associated with raloxifene was greater in women at high stroke risk. These results might be useful for identifying postmenopausal women at high risk of first stroke who should avoid raloxifene therapy.