Phase 2 clinical trial of a vaginal mucosal vaccine for urinary tract infections

PURPOSE: Recurrent urinary tract infections (UTIs) in susceptible women remain a common urological condition. With an increasing number of UTIs being caused by antibiotic resistant bacteria there is a need for alternatives to antibiotics. We determined whether multiple doses of a vaginal mucosal vaccine are effective for increasing long-term resistance to recurrent UTIs. MATERIALS AND METHODS: A total of 54 women were entered into a double-blind, placebo controlled, phase 2 clinical trial using a vaginal vaccine containing 10 heat killed uropathogenic bacteria. Patients were withdrawn from prophylactic antibiotics and randomly assigned to 1 of 3 treatment groups, namely placebo only, primary immunization or primary plus booster immunizations. Subjects received treatments at 0, 1, 2, 6, 10 and 14 weeks. Placebo treated patients received suppositories without bacteria. The primary immunization group received vaccine suppositories, followed by 3 doses of placebo. Patients receiving booster immunizations were given 6 vaccine suppositories. All women were followed for 6 months to determine the time until first recurrence, number of infections and adverse reactions. RESULTS: Women receiving 6 vaccine doses remained free of infections for a significantly longer period than those receiving placebo or primary immunizations. Of patients receiving 6 immunizations 55% did not experience an infection, whereas 89% of placebo treated women had UTIs. No women had significant adverse effects. CONCLUSIONS: This study demonstrates that vaginal mucosal vaccine given for a 14-week period increased the time to re-infection in UTI susceptible women. The infrequent, minimal adverse reactions confirm previous observations on the safety of this vaginal mucosal immunization regimen.     

The use of ECG and respiratory triggering to improve the sensitivity of oxygen-enhanced proton MRI of lung ventilation

Changes in lung signal between normal breathing and breathing pure oxygen is the basis for oxygen-enhanced ventilation MRI. An optimal technique guarantees a significant response to pure oxygen in well-ventilated lung tissue. To improve the sensitivity, we investigated the effect of ECG and respiratory triggering. Centric reordered single-shot rapid acquisition relaxation enhancement sequences (TE 4.2 ms, echo spacing 4.2 ms, bandwidth 650 Hz/pixel), with an inversion recovery preparation pulse (TI 700 ms), were used. Series of 20 measurements were performed with and without ECG and respiratory triggering in five young volunteers. Subsequently, series of 100 images were acquired during breathing normal air and pure oxygen (as "stimulus"). Ventilation maps showed by means of the z-score how far the response deviates from the signal intensities during the normal air condition. The standard deviation of the lung signal intensities was lowest for the cardiac-triggered series. In the ventilation maps, on the other hand, signal changes were statistically more significant in the respiratory than in the cardiac-triggered series. The average z-scores in the right (left) cranial part of the lung were 12.4 (13.0) and 9.2 (9.7) for respiratory and ECG-triggered acquisitions. We propose to use respiratory triggering as a means to improve the sensitivity of MR ventilation studies. Electronic Publication     

Respiratory symptoms and ventilatory function in workers exposed to portland cement dust

The healthy worker effect and incomplete exposure information have been problems in former studies regarding the association between exposure to Portland cement dust and respiratory effects. We included former workers and made an individual estimation of particle exposure to reduce the selection bias in this controlled cross-sectional study on the effects of cement dust exposure on respiratory symptoms and ventilatory function in long-term exposed Norwegian cement plant workers. A total of 119 workers from the largest cement plant in Norway and 50 workers from a nearby control plant, born 1918 to 1938, performed spirometry and gave information on respiratory symptoms in 1998 and 1999. The prevalence of symptoms and mean pulmonary function indices were similar for exposed workers and controls. There was no dose-response-related increase in symptoms or decrease in lung function indices. The estimated power to detect a true difference between forced expiratory volume in one second (FEV1) in the two groups of 0.3l was 0.90, assuming 95% significance level. The prevalence of chronic obstructive pulmonary disease was 14.3% in the exposed group and 14.0% among the controls. These findings do not support the hypothesis that cement dust exposure has a negative impact on lung function or gives an increase in respiratory symptoms.     

Role of fluorine-18 fluoro-deoxyglucose positron emission tomography scan in the evaluation and follow-up of patients with low-grade lymphomas

BACKGROUND: Fluorine-18 fluoro-deoxyglucose positron emission tomography (FDG-PET) scanning has excellent sensitivity and specificity for staging non-Hodgkin lymphomas, but to the authors' knowledge few studies to date have evaluated FDG-PET in low-grade lymphomas only. METHODS: A retrospective study was performed on patients with biopsy-proven nontransformed and transformed follicular lymphoma (FL), B-cell small-cell lymphocytic lymphoma (SLL/CLL), or marginal zone lymphoma (MZL) who underwent PET and computed tomography (CT) scans within 3 weeks. Standard uptake values (SUV) of all abnormal foci were measured. RESULTS: In FL, PET demonstrated 94% sensitivity and 100% specificity for staging. PET was more specific than CT for detecting recurrence or assessing therapeutic responses (91% vs. 50%). FDG avidity among patients with WHO Grades 1, 2, and 3 disease was not significantly different (analysis of variance [ANOVA]). For MZL staging, PET had moderate sensitivity (71%) and outperformed CT alone in the depiction of extranodal sites (85% vs. 57% sensitivity). In SLL/CLL, PET sensitivity was 53% and underestimated disease extent in 5 of 19 patients (26%) compared with CT. PET did not affect initial management but confirmed suspected recurrences in 75% of patients. Nontransformed FL had a higher SUV (ANOVA, P < .05) compared with MZL and SLL/CLL. SUV was higher in transformed than in nontransformed tumors (P < .001, Student t test). CONCLUSIONS: PET usefulness in staging low-grade lymphomas varies depending on histology. PET sensitivity is excellent in FL and moderate in MZL. PET is more specific than CT for follow-up in all types. PET has limited usefulness for SLL/CLL staging. However, a suggestive pattern of hazy and mild uptake was often noted in positive scans. In all low-grade lymphomas, the emergence of foci of intense uptake should raise suspicion of conversion to high-grade disease.     

Limited value of shape, margin and CT density in the discrimination between benign and malignant screen detected solid pulmonary nodules of the NELSON trial

Purpose

To evaluate prospectively the value of size, shape, margin and density in discriminating between benign and malignant CT screen detected solid non-calcified pulmonary nodules.

Material and methods

This study was institutional review board approved. For this study 405 participants of the NELSON lung cancer screening trial with 469 indeterminate or potentially malignant solid pulmonary nodules (>50 mm³) were selected. The nodules were classified based on size, shape (round, polygonal, irregular) and margin (smooth, lobulated, spiculated). Mean nodule density and nodule volume were automatically generated by software. Analyses were performed by univariate and multivariate logistic regression. Results were presented as likelihood ratios (LR) with 95% confidence intervals (CI). Receiver operating characteristic analysis was performed for mean density as predictor for lung cancer.

Results

Of the 469 nodules, 387 (83%) were between 50 and 500 mm³, 82 (17%) >500 mm³, 59 (13%) malignant, 410 (87%) benign. The median size of the nodules was 103 mm³ (range 50–5486 mm³). In multivariate analysis lobulated nodules had LR of 11 compared to smooth; spiculated nodules a LR of 7 compared to smooth; irregular nodules a LR of 6 compared to round and polygonal; volume a LR of 3. The mean nodule CT density did not predict the presence of lung cancer (AUC 0.37, 95% CI 0.32–0.43).

Conclusion

In solid non-calcified nodules larger than 50 mm³, size and to a lesser extent a lobulated or spiculated margin and irregular shape increased the likelihood that a nodule was malignant. Nodule density had no discriminative power.