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.

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.

IL-6 is a biological marker of ventilator-associated lung injury that may contribute to alveolar barrier dysfunction in acute respiratory distress syndrome. To determine whether IL-6 affects alveolar barrier disruption in a model of ventilator-induced lung injury, we examined alveolar barrier albumin flux in wild-type (WT) mice given an IL-6-blocking Ab (IL6AB) and mice deficient in IL-6 (IL6KO). Albumin flux was significantly higher in mice given IL6AB compared with mice given a control Ab. Unexpectedly, albumin flux was similar in WT and IL6KO mice. To examine the mechanisms for these findings, lung neutrophil accumulation (myeloperoxidase activity) was compared, revealing a correlation between lung neutrophil accumulation and albumin flux. IL6AB mice had significantly more lung neutrophils than WT and IL6KO mice, which were similar. Therefore, to determine whether the cellular source of IL-6 influences neutrophil accumulation and alveolar barrier function, chimeric mice were compared. WT/KO chimeras (WT mice with IL6KO hematopoietic cells) showed significantly greater albumin flux and neutrophil accumulation with mechanical ventilation than WT/WT mice. Neutrophil depletion decreased albumin flux in WT and WT/KO mice. IL6KO neutrophils were more adherent in an in vitro assay compared with WT neutrophils. IL-6 from a hematopoietic cell source limits alveolar barrier disruption potentially by reducing neutrophil contact with the endothelium. Modulation of IL-6 signaling in a cell type-specific fashion may be a therapeutic target for patients with acute lung injury.

BACKGROUND AND AIM

The endoscopic landmark of esophagogastric junction (EGJ) for diagnosis of Barrett's esophagus (BE) differs between Japan and Western countries. Japanese endoscopists use the distal end of the lower esophageal palisade vessels to localize EGJ. In the West, endoscopists use the proximal gastric folds because of concerns that palisade vessels may be difficult to recognize. We evaluated whether there were differences between American and Japanese endoscopists in the recognition of palisade vessels.

METHOD

A total of 82 patients were enrolled in this study. Patients were referred for diagnostic esophagogastroduodenoendoscopy (EGD) at the Veterans Affairs Palo Alto Health Care System, from May to July 2008. American and Japanese endoscopists evaluated the EGJ of patients undergoing diagnostic EGD. We analyzed the differences in the recognition of the distal end of palisade vessels. We calculated the kappa statistic to measure interobserver variability.

RESULTS

Based on localization using the distal end of the palisade vessels, American and Japanese endoscopists identified the EGJ in 87.8% (72/82) and 89.0% (73/82) of cases, respectively. The kappa statistic for visualization of EGJ was 0.88 [95% confidence interval (CI): 0.73-1.00].

CONCLUSION

American and Japanese endoscopists similarly recognized the distal end of palisade vessels as EGJ.

OBJECTIVE

To determine whether the flight attendants who were exposed to secondhand tobacco smoke in the aircraft cabin have abnormal pulmonary function.

METHODS

We administered questionnaires and performed pulmonary function testing in 61 never-smoking female flight attendants who worked in active air crews before the smoking ban on commercial aircraft (preban).

RESULTS

Although the preban flight attendants had normal FVC, FEV1, and FEV1/FVC ratio, they had significantly decreased flow at mid- and low-lung volumes, curvilinear flow-volume curves, and evidence of air trapping. Furthermore, the flight attendants had significantly decreased diffusing capacity (77.5% +/- 11.2% predicted normal) with 51% having a diffusing capacity below their 95% normal prediction limit.

CONCLUSIONS

This cohort of healthy never-smoking flight attendants who were exposed to secondhand tobacco smoke in the aircraft cabin showed pulmonary function abnormalities suggestive of airway obstruction and impaired diffusion.