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1.  Repeat Post-Op Voiding Trials: An Inconvenient Correlate with Success 
Neurourology and urodynamics  2013;33(8):1225-1228.
This study examined the association between the need for a repeat voiding trial after midurethral sling (MUS) surgery and 1-year success rates.
We conducted this secondary analysis of the participants in the Urinary Incontinence Treatment Network Trial Of Midurethral Sling (TOMUS) study which compared retropubic vs. transobturator MUS. A standard voiding trial was attempted on all subjects. The ‘repeat voiding trial’ group included subjects discharged with catheterization. All others were considered ‘self voiding’. Success rates between the groups at 1 year were compared, followed by multivariate analyses controlling for previously reported clinical predictors of success.
Most women (76%) were self-voiding, while 24% required a repeat voiding trial. The objective success rate at 1 year was 85.8% in the repeat voiding trial group and 75.3% in the self-voiding group (p=0.01). Subjective success rate at 1 year was 61.0% in the repeat voiding trial group and 55.1% in the self-voiding group (p=0.23). Women in the repeat voiding trial group continued to demonstrate greater objective success than the self-voiding group in multivariate analysis that controlled for previous incontinence surgery, pad weight, urethral mobility, urge score and type of MUS (p=0.04, OR 1.82, 95% CI 1.03-3.22).
Women who require a repeat voiding trial following MUS surgery have greater objective success at 1 year postoperatively when compared to those who are self-voiding at the time of discharge. These results may help reassure women who require catheterization after MUS surgery that their outcome is not compromised by this immediate transient postoperative result.
PMCID: PMC3937293  PMID: 23983149
Stress Urinary Incontinence; Voiding Dysfunction; Midurethral Sling
2.  Magnetic Resonance Relaxometry at Low and Ultra low Fields 
IFMBE proceedings  2010;28:82-87.
Nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) are ubiquitous tools in science and medicine. NMR provides powerful probes of local and macromolecular chemical structure and dynamics. Recently it has become possible and practical to perform MR at very low fields (from 1 μT to 1 mT), the so-called ultra-low field (ULF) regime. Pulsed pre-polarizing fields greatly enhance the signal strength and allow flexibility in signal acquisition sequences. Improvements in SQUID sensor technology allow ultra-sensitive detection in a pulsed field environment.
In this regime the proton Larmor frequencies (1 Hz – 100 kHz) of ULF MR overlap (on a time scale of 10 μs to 100 ms) with “slow” molecular dynamic processes such as diffusion, intra-molecular motion, chemical reactions, and biological processes such as protein folding, catalysis and ligand binding. The frequency dependence of relaxation at ultra-low fields may provide a probe for biomolecular dynamics on the millisecond timescale (protein folding and aggregation, conformational motions of enzymes, binding and structural fluctuations of coupled domains in allosteric mechanisms) relevant to host-pathogen interactions, biofuels, and biomediation. Also this resonance-enhanced coupling at ULF can greatly enhance contrast in medical applications of ULF-MRI resulting in better diagnostic techniques.
We have developed a number of instruments and techniques to study relaxation vs. frequency at the ULF regime. Details of the techniques and results are presented.
Ultra-low field methods are already being applied at LANL in brain imaging, and detection of liquid explosives at airports. However, the potential power of ultra-low field MR remains to be fully exploited.
PMCID: PMC3142879  PMID: 21796269
ultra-low field; nuclear magnetic resonance; relaxation
3.  Quality of Life after Surgery for Stress Incontinence 
This study investigated changes in condition-specific quality of life (QOL) after surgery for stress urinary incontinence (SUI).
Data from 655 women in a clinical trial comparing the Burch and fascial sling were examined.
Improvement in QOL, measured with the IIQ (mean decrease 133.1; s.d. 109.8), was observed 6 months after surgery and persisted at 24 months. Women for whom surgery was successful (regardless of surgery type) had greater improvement in QOL (mean decrease 160.0; s.d 103.9) than did women for whom surgery was not successful (mean decrease 113.6; s.d 110.9) (p<0.0001), although not statistically significant after adjusting for covariates. Multivariable analysis showed that QOL improvement was related to decreased UI symptom bother, greater improvement in UI severity, younger age, Hispanic ethnicity and receiving Burch surgery. Among sexually active women, worsening sexual function had a negative impact on QOL.
Improved QOL was explained most by UI symptom improvement.
Brief Summary
Improvements in quality of life after stress incontinence surgery are significant, durable over 24 months, and associated with improvement of incontinence symptoms and symptom bother.
PMCID: PMC2576493  PMID: 18682875
Quality of life; surgery; urinary incontinence
8.  DNA single strand breakage, DNA adducts, and sister chromatid exchange in lymphocytes and phenanthrene and pyrene metabolites in urine of coke oven workers. 
OBJECTIVES: To investigate the specificity of biological monitoring variables (excretion of phenanthrene and pyrene metabolites in urine) and the usefulness of some biomarkers of effect (alkaline filter elution, 32P postlabelling assay, measurement of sister chromatid exchange) in workers exposed to polycyclic aromatic hydrocarbons (PAHs). METHODS: 29 coke oven workers and a standardised control group were investigated for frequencies of DNA single strand breakage, DNA protein cross links (alkaline filter elution assay), sister chromatid exchange, and DNA adducts (32P postlabelling assay) in lymphocytes. Phenanthrene and pyrene metabolites were measured in 24 hour urine samples. 19 different PAHs (including benzo(a)pyrene, pyrene, and phenanthrene) were measured at the workplace by personal air monitoring. The GSTT1 activity in erythrocytes and lymphocyte subpopulations in blood was also measured. RESULTS: Concentrations of phenanthrene, pyrene, and benzo(a)pyrene in air correlated well with the concentration of total PAHs in air; they could be used for comparisons of different workplaces if the emission compositions were known. The measurement of phenanthrene metabolites in urine proved to be a better biological monitoring variable than the measurement of 1-hydroxypyrene. Significantly more DNA strand breaks in lymphocytes of coke oven workers were found (alkaline filter elution assay); the DNA adduct rate was not significantly increased in workers, but correlated with exposure to PAHs in a semiquantitative manner. The number of sister chromatid exchanges was lower in coke oven workers but this was not significant; thus counting sister chromatid exchanges was not a good variable for biomonitoring of coke oven workers. Also, indications for immunotoxic influences (changes in lymphocyte subpopulations) were found. CONCLUSIONS: The measurement of phenanthrene metabolites in urine seems to be a better biological monitoring variable for exposure to PAHs than measurement of hydroxypyrene. The alkaline filter elution assay proved to be the most sensitive biomarker for genotoxic damage, whereas the postlabelling assay was the only one with some specificity for DNA alterations caused by known compounds.
PMCID: PMC1128680  PMID: 9155778
9.  Direct modulation of simian virus 40 late gene expression by thyroid hormone and its receptor. 
Journal of Virology  1997;71(1):427-436.
Transcription of the late genes of simian virus 40 (SV40) is repressed during the early phase of the lytic cycle of infection of primate cells by the binding of cellular factors, called IBP-s, to the SV40 late promoter; repression is relieved after the onset of viral DNA replication by titration of these repressors (S. R. Wiley, R. J. Kraus, F. R. Zuo, E. E. Murray, K. Loritz, and J. E. Mertz, Genes Dev. 7:2206-2219, 1993). Recently, we showed that IBP-s consists of several members of the steroid/thyroid hormone receptor superfamily (F. Zuo and J. E. Mertz, Proc. Natl. Acad. Sci. USA 92:8586-8590, 1995). Here, we show that the thyroid hormone receptor TRalpha1, in combination with retinoid X receptor alpha (RXRalpha), is specifically bound at the transcriptional initiation site of the major late promoter of SV40. This binding repressed transcription from the SV40 late promoter by preventing the formation of pre-initiation complexes. Addition of the thyroid hormone 3,5,3'-L-triiodothyronine (T3) resulted in reversal of this repression in cotransfected CV-1 cells. Interestingly, repression did not occur when this thyroid response element (TRE) was translocated to 50 bp upstream of the major late initiation site. Binding of TRalpha1/RXRalpha heterodimers to this TRE induced bending of the promoter DNA. We conclude that hormones and their receptors can directly affect the expression of SV40, probably by affecting protein-protein and protein-DNA interactions involved in the formation of functional preinitiation complexes.
PMCID: PMC191068  PMID: 8985367
10.  Experimentally determined weight matrix definitions of the initiator and TBP binding site elements of promoters. 
Nucleic Acids Research  1996;24(8):1531-1539.
The basal elements of class II promoters are: (i) a-30 region, recognized by TATA binding protein (TBP); (ii) an initiator (Inr) surrounding the start site for transcription; (iii) frequently a downstream (+10 to +35) element. To determine the sequences that specify an Inr, we performed a saturation mutagenesis of the Inr of the SV40 major late promoter (SV40-MLP). The transcriptional activity of each mutant was determined both in vivo and in vitro. An excellent correlation between transcriptional activity and closeness of fit to the optimal Inr sequence, 5'-CAG/TT-3', was found to exist both in vivo and in vitro. Employing a neural network technique we generated from these data a weight matrix definition of an Inr that can be used to predict the activity of a given sequence as an Inr. Using saturation mutagenesis data of TBP binding sites we likewise generated a weight matrix definition of the -30 region element. We conclude the following: (i) Inrs are defined by the nucleotides immediately surrounding the transcriptional start site; (ii) most, if not all, Inrs are recognized by the same general transcription factor(s). We propose that the mechanism of transcription initiation is fundamentally conserved, with the formation of pre-initiation complexes involving the concurrent binding of general transcription factors to the -30, Inr and, possibly, downstream elements of class II promoters.
PMCID: PMC145818  PMID: 8628688
11.  Activity testing of alveolar macrophages and changes in surfactant phospholipids after irradiation in bronchoalveolar lavage: experimental and clinical data. 
This study presents results of bronchoalveolar lavage (BAL) after irradiation to the lungs in mice as well as clinical data. The number of BAL cells, mainly macrophages, lymphocytes, and granulocytes, changed in a time-dependent manner. The phagocytic activity of the macrophages measured as the phagocytosis of microbeads and measured as the esterase activity also showed a strong time-dependent increase during the acute phase up to 21 days after irradiation. The contents of surfactant phospholipids (SF) and sphingomyelin (SPH; as a parameter for cell death) were quantified by HPLC. Both were significantly changed between day 2 and 21 after irradiation. Three BALs of a patient with idiopathic interstitial pneumonitis, who had received an allogenic bone marrow graft after total body irradiation with 10 Gy, showed similar effects in the cellular and surfactant parameters. These data indicate that there are positive interactions between the number of different BAL cells, macrophage activity, and SF and SPH content in the preclinical model of the mouse as well as in the clinical situation after lung irradiation.
PMCID: PMC1519533  PMID: 1396455
12.  Tolterodine extended release is well tolerated in older subjects 
To investigate the tolerability of tolterodine extended release (ER) in older subjects with overactive bladder (OAB).
This was a retrospective analysis of pooled data from five large, randomised, double-blind, placebo-controlled trials. Subjects with OAB symptoms, including urinary frequency and urgency (and nocturia in two studies) with or without urgency urinary incontinence, received qd treatment with tolterodine ER (4 mg) or placebo for 8–12 weeks. Data were stratified post hoc by age group: < 65 (n = 2531), 65–74 (n = 1059) and ≥ 75 years (n = 573). Tolerability was assessed by evaluating the occurrence of adverse events (AEs). AE occurrences from each study were mapped to the MedDRA coding dictionary of preferred terms.
Discontinuation rates were slightly higher among subjects ≥ 75 years of age vs. those < 65 years of age; however, this was observed in subjects treated with placebo as well as tolterodine ER. Overall, there were no significant differences in the occurrence of dry mouth, headache, constipation, nausea, urinary tract infection, blurred vision, dry eye, dizziness and micturition disorder in older (65–74 or ≥ 75 years) vs. younger (< 65 years) subjects treated with tolterodine ER relative to placebo (treatment × age; all p > 0.1). Dry mouth was the only AE consistently associated with tolterodine ER treatment (< 65 years, 17%; 65–74 years, 16%; ≥ 75 years, 15%). The occurrence of all other AEs was ≤ 5% in most age and treatment cohorts. Most AEs were mild or moderate in all age and treatment cohorts.
The nature and frequency of AEs associated with tolterodine ER treatment were similar across age groups in subjects with OAB, suggesting that tolterodine ER was not associated with an increased risk of AEs in older vs. younger subjects and, thus, is a suitable first-line pharmacotherapy treatment for OAB in this population.
PMCID: PMC2737749  PMID: 19624787

Results 1-12 (12)