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Urinary frequency [keywords]
- Urinary Metabolite Profiling Combined with Computational Analysis Predicts Interstitial Cystitis-Associated Candidate Biomarkers. [JOURNAL ARTICLE]
- J Proteome Res 2014 Oct 29.
Interstitial cystitis/painful bladder syndrome (IC) is a chronic syndrome of unknown etiology that presents with bladder pain, urinary frequency, and urgency. The lack of specific biomarkers and a poor understanding of underlying molecular mechanisms presents challenges for disease diagnosis and therapy. The goals of this study were to identify non-invasive biomarker candidates for IC from urine specimens and potentially gain new insight into disease mechanisms using a nuclear magnetic resonance (NMR)-based global metabolomics analysis of urine from female IC patients and controls. Principal component analysis (PCA) suggested that the urinary metabolome of IC and controls was clearly different, with 140 NMR peaks significantly altered in IC patients (FDR<0.05), compared to controls. Based on strong correlation scores, eight metabolite peaks were nominated as the strongest signature of IC. Among those signals that were higher in the IC groups, three peaks were annotated as tyramine, the pain-related neuromodulator. Two peaks were annotated as 2-oxoglutarate. Levels of tyramine and 2-oxoglutarate were significantly elevated in urine specimens of IC subjects. An independent analysis using mass spectrometry also showed the significantly increased levels of tyramine and 2-oxoglutarate in IC patients, compared to controls. Functional studies showed that 2-oxoglutarate, but not tyramine, retarded growth of normal bladder epithelial cells. These preliminary findings suggest that analysis of urine metabolites has promise in biomarker development in the context of IC.
- Reductions in urinary collection frequency for assessment of reproductive hormones provide physiologically representative exposure and mean concentrations when compared with daily collection. [JOURNAL ARTICLE]
- Am J Hum Biol 2014 Oct 29.
To determine if reducing the frequency of urinary sample collection from daily to 5, 3, or 2 days per week during a menstrual cycle or 28-day amenorrheic monitoring period provide accurate representations of the reproductive hormone metabolites estrone-1-glucuronide (E1G) and pregnanediol glucuronide (PdG) exposure and mean concentrations.Exercising women presenting with eumenorrhea or exercise-associated menstrual disturbances collected daily urine samples for the assessment of E1G and PdG concentrations. After enzyme immunoassay analysis of the daily samples, E1G and PdG data were systematically removed from each menstrual cycle or amenorrheic monitoring period to mimic three reduced collection frequencies, representing 5, 3, and 2 days per week. Exposure and mean concentration were calculated for both hormones and all four urinary collection frequencies.E1G and PdG exposure and mean cycle concentrations derived from reduced collection frequencies were not different from daily collection (P > 0.05), independent of whether menstrual cycles and monitoring periods were analyzed together or separately. Bland-Altman analysis indicated acceptable agreement between each reduced collection frequency and daily collection.Compared with daily urinary collection, a reduced collection frequency of 5, 3, or 2 days each week provides accurate E1G and PdG profiles of collection periods of various lengths and types of menstrual function. Reduction of urinary sample collection frequency may enable researchers to reduce participant burden and costs, increase compliance, and study a wider range of study populations. Am. J. Hum. Biol., 2014. © 2014 Wiley Periodicals, Inc.
- Polygenic Overlap Between Kidney Function and Large Artery Atherosclerotic Stroke. [JOURNAL ARTICLE]
- Stroke 2014 Oct 28.
Epidemiological studies show strong associations between kidney dysfunction and risk of ischemic stroke (IS), the mechanisms of which are incompletely understood. We investigated whether these associations may reflect shared heritability because of a common polygenic basis and whether this differed for IS subtypes.Polygenic models were derived using genome-wide association studies meta-analysis results for 3 kidney traits: estimated glomerular filtration rate using serum creatinine (eGFRcrea: n=73 998), eGFR using cystatin C (eGFRcys: n=22 937), and urinary albumin to creatinine ratio (n=31 580). For each, single nucleotide polymorphisms passing 10 P value thresholds were used to form profile scores in 4561 IS cases and 7094 controls from the United Kingdom, Germany, and Australia. Scores were tested for association with IS and its 3 aetiological subtypes: large artery atherosclerosis, cardioembolism, and small vessel disease.Polygenic scores correlating with higher eGFRcrea were associated with reduced risk of large artery atherosclerosis, with 5 scores reaching P<0.05 (peak P=0.004) and all showing the epidemiologically expected direction of effect. A similar pattern was observed for polygenic scores reflecting higher urinary albumin to creatinine ratio, of which 3 associated with large artery atherosclerosis (peak P=0.01) and all showed the expected directional association. One urinary albumin to creatinine ratio-based score also associated with small vessel disease (P=0.03). The global pattern of results was unlikely to have occurred by chance (P=0.02).This study suggests possible polygenic correlation between renal dysfunction and IS. The shared genetic components may be specific to stroke subtypes, particularly large artery atherosclerotic stroke. Further study of the genetic relationships between these disorders seems merited.
- Magnitude of daily energy deficit predicts frequency but not severity of menstrual disturbances associated with exercise and caloric restriction. [JOURNAL ARTICLE]
- Am J Physiol Endocrinol Metab 2014 Oct 28.:ajpendo.00386.2013.
We assessed the impact of energy deficiency on menstrual function using controlled feeding and supervised exercise over four menstrual cycles (1 Baseline and 3 Intervention cycles) in untrained, eumenorrheic women ages 18-30 yrs. Subjects were randomized to either an exercising control (EXCON) or one of three exercising energy deficit (ED) groups i.e., mild (ED1) (-8 ± 2%), moderate (ED2) (-22 ± 3%), or severe (ED3) (-42 ± 3%). Menstrual cycle length and changes in urinary concentrations of estrone-1-glucuronide, pregnanediol glucuronide, and mid-cycle luteinizing hormone were assessed. Thirty-four subjects completed the study. Weight loss occurred in ED1 (- 3.8 ± 0.2 kg), ED2 (- 2.8 ± 0.6 kg), and ED3 (- 2.6 ± 1.1 kg), but was minimal in EXCON (-0.9 ± 0.7 kg). The overall sum of disturbances (luteal phase defects, anovulation, and oligomenorrhea) was greater in ED2 compared to EXCON and greater in ED3 compared to EXCON AND ED1. The average percent energy deficit was the main predictor of the frequency of menstrual disturbances (f = 10.1; β= -0.48; R2=0.23; p=0.003) even when including weight loss in the model. The estimates of the magnitude of energy deficiency associated with menstrual disturbances ranged from -22% (ED2) to -42% (ED3), reflecting an energy deficit of -470 to -810 kcal per day, respectively. This is the first study to demonstrate a dose response relation between the magnitude of energy deficiency and the frequency of exercise-related menstrual disturbances; however, the severity of menstrual disturbances was not dependent on the magnitude of energy deficiency.
- General effect of low-dose tamsulosin (0.2 mg) as a first-line treatment for lower urinary tract symptoms associated with benign prostatic hyperplasia: a systematic review and meta-analysis. [JOURNAL ARTICLE]
- Curr Med Res Opin 2014 Oct 28.:1-36.
Abstract Purpose In Asian countries, low-dose tamsulosin (0.2 mg) is used widely but this dose has been less popular than 0.4 mg tamsulosin or other types of alpha blockers. The aim of this study was to investigate the efficacy and safety of low-dose tamsulosin by systematic review and meta-analysis. Methods We conducted a meta-analysis of improvements of lower urinary tract symptoms using International Prostate Symptom Score (IPSS), maximal urinary flow rate (Qmax), post-voided residual volume (PVR), and quality of life (QOL). Relevant studies were found using MEDLINE, EMBASE, and the Cochrane library. Final inclusion was determined by RCTs and performance of IPSS. Results A total of fourteen studies were included, with a total sample size of 2,147 subjects (1,044 experimental and 1,103controls). Study durations ranged from 4 to 52 weeks. The mean change of IPSS improvement from baseline for tamsulosin was -7.18 (95% CI -7.83, -6.54). The mean change of QOL improvement from baseline was -1.34 (95% CI; -1.46, -1.22). The overall Qmax improvement from baseline was 2.32 ml/sec (95% CI; 1.95, 2.70). The mean change of PVR improvement from baseline was -11.12 ml (95% CI; -17.61, -4.64). Regarding safety, four studies did not report any adverse events while others reported that adverse events were all tolerated. Conclusions Although this study did not consider placebo effect and has high IPSS baseline scores, this study clarifies that low-dose tamsulosin has general positive effect and safety in treatment of LUTS and could be a suitable option as an initial treatment, especially for patients with small body mass index, as is typical of Asian people.
- Effect of Intravesical Botulinum Neurotoxin-A Injection on Detrusor Hyperreflexia in Spinal Cord Injured Patients. [JOURNAL ARTICLE]
- Drug Res (Stuttg) 2014 Oct 28.
Purpose: To evaluate the effects of Botulinum Toxin A injection into the detrusor muscle on various voiding parameters in spinal cord injured patients with neurogenic detrusor hyperreflexia Materials and methods: 24 patients with spinal cord injuries who had detrusor overactivity and urinary incontinence and were refractory to oral medications, were injected 300 IU of BTX-A into the detrusor muscle. The pre-and post-treatment evaluations included determination of bladder urinary continence status, frequency/volume chart of CIC, Incontinence Quality of Life questionnaire (I-QOL) and patient satisfaction. The urodynamic parameters measured included maximum cystometric capacity (MCC), reflex detrusor volume (RDV) and maximum detrusor pressure during bladder contraction (MDP) were analyzed at the outset and during the follow-up (2, 6, and 24 weeks) examinations. Results: The evaluation of urodynamic parameters during follow-up examinations (2, 6 and 24 weeks) revealed significant increase in mean reflex volume (p<0.05) and cystometric capacity (p<0.05), on the other detrusor pressure decreased significantly (p<0.05). In majority of patients there was considerable reduction in incontinence episodes and no complications or side effects were reported. Most of the patents were satisfied with the treatment. Conclusion: The use of Botulinum toxin type A for treatment of neurogenic detrusor overactivity in spinal cord injured patients is safe and efficacious. In our 24-week study period, there was significant improvement in most urodynamic parameters with consistence and subjective satisfaction indicated by the treated patients.
- Tolterodine extended release in the treatment of male oab/storage luts: a systematic review. [JOURNAL ARTICLE]
- BMC Urol 2014 Oct 27; 14(1):84.
Overactive bladder (OAB)/ storage lower urinary tract symptoms (LUTS) have a high prevalence affecting up to 90% of men over 80 years. The role of sufficient therapies appears crucial. In the present review, we analyzed the mechanism of action of tolterodine extended-release (ER) with the aim to clarify its efficacy and safety profile, as compared to other active treatments of OAB/storage LUTS.A wide Medline search was performed including the combination of following words: "LUTS", "BPH", "OAB", "antimuscarinic", "tolterodine", "tolterodine ER". IPSS, IPSS storage sub-score and IPSS QoL (International Prostate Symptom Score) were the validated efficacy outcomes. In addition, the numbers of urgency episodes/24 h, urgency incontinence episodes/24 h, incontinence episodes/24 h and pad use were considered. We also evaluated the most common adverse events (AEs) reported for tolterodine ER.Of 128 retrieved articles, 109 were excluded. The efficacy and tolerability of tolterodine ER Vs. tolterodine IR have been evaluated in a multicenter, double-blind, randomized placebo controlled study in 1529 patients with OAB. A 71% mean reduction in urgency incontinence episodes was found in the tolterodine ER group compared to a 60% reduction in the tolterodine IR (p < 0.05). Few studies evaluated the clinical efficacy of alpha-blocker/tolterodine combination therapy. In patients with large prostates (prostate volume >29 cc) only the combination therapy significantly reduced 24-h voiding frequency (2.8 vs. 1.7 with tamsulosin, 1.4 with tolterodine, or 1.6 with placebo). A recent meta-analysis evaluating tolterodine in comparison with other antimuscarinic drugs demonstrated that tolterodine ER was significantly more effective than placebo in reducing micturition/24 h, urinary leakage episodes/24 h, urgency episodes/24 h, and urgency incontinence episodes/24 h. With regard to adverse events, tolterodine ER was associated with a good adverse event profile resulting in the third most favorable antimuscarinic. Antimuscarinic drugs are the mainstay of pharmacological therapy for OAB / storage LUTS; several studies have demonstrated that tolterodine ER is an effective and well tolerated formulation of this class of treatment.Tolterodine ER resulted effective in reducing frequency urgency and nocturia and urinary leakage in male patients with OAB/storage LUTS. Dry mouth and constipation are the most frequently reported adverse events.
- Pain in Renal Disease. [JOURNAL ARTICLE]
- J Pain Palliat Care Pharmacother 2014 Oct 28.
ABSTRACT Pain is the presenting symptom in 20 to 30% of patients with autosomal dominant polycystic kidney disease (ADPKD) and occurs in 50 to 60% of patients at some stage of the disease process, but its frequency increases with age and size of the cysts. Back pain is caused by kidney enlargement as well as rupture, hemorrhage, or infection of cysts. Other causes of pain include nephrolithiasis and urinary tract infections (UTIs). Analgesic options for patients with ADPKD include transcutaneous electrical nerve stimulation (TENS), spinal cord stimulation, low-dose opioids, and local anesthetics.
- Urodynamic characterization of lower urinary tract symptoms in women less than 40 years of age. [JOURNAL ARTICLE]
- Can J Urol 2014 Oct; 21(5):7460-7464.
Lower urinary tract symptoms (LUTS) in young women is becoming a more recognized urologic issue that can arise from many causes, each with their own management strategy. The purpose of this study was to determine the rates of various etiologies for LUTS in women under 40 years of age.Video urodynamic studies (VUDS) were performed in 70 women age 40 years or less with LUTS for greater than 6 months between March 2005 and June 2012 at Weill Cornell Medical College. Patients with culture-proven bacterial urinary tract infections, pelvic organ prolapse greater than grade I, symptoms for less than 6 months, a history of neurologic disease, or previous urological surgery affecting voiding function, were excluded from the analysis.The mean age of the patients was 31.95 ± 5.57. There were 48 patients that presented with more than one urinary symptom (68.57%). The most frequent complaints included: urinary frequency (n = 42, 34.15%), incontinence (n = 26, 21.14%), and urinary urgency (n = 22, 17.89%). The most common urodynamic abnormality was dysfunctional voiding (n = 25, 28.74%), detrusor overactivity (n = 15, 20.00%), bladder outlet obstruction (n = 8, 11.43%). There were no significant differences seen in complaints or AUA symptom and quality of life scores across diagnosis groups.Persistent LUTS can present in younger women with an unclear etiology, which may be characterized using VUDS. The most common etiology found is dysfunctional voiding followed by detrusor overactivity. This study shows that the etiology can be more accurately determined using VUDs, which can assist in management.
- Evaluation of genotoxicity in workers exposed to benzene and atmospheric pollutants. [JOURNAL ARTICLE]
- Mutat Res Genet Toxicol Environ Mutagen 2014 Aug.:61-65.
Gas station attendants and taxi drivers are occupationally exposed to xenobiotics which may be harmful to their health. Atmospheric pollutants and benzene can lead to DNA damage. Genotoxicity and mutagenicity assays can be used to evaluate the effects of these pollutants. We have evaluated genotoxicity and mutagenicity in workers occupationally exposed to xenobiotics, by application of the 8-hydroxy-2-deoxyguanosine (8-OHdG), comet, and micronucleus (MN) assays. Biomarkers of benzene and carbon monoxyde exposure were also measured: urinary t,t-muconic acid (t,t-MA) and carboxyhaemoglobin (COHb) in whole blood, respectively. The study groups comprised 43 gas station attendants (GSA), 34 taxi drivers (TD), and 22 persons without known occupational exposures (NE). Levels of t,t-MA in the GSA group were significantly elevated compared to the NE group (p<0.001), however these levels were below of levels established by ACGIH (American Conference of Governmental Industrial Hygienists). COHb levels were not significantly different between the TD and NE groups (p>0.05). DNA damage index (DI) and 8-OHdG levels were significantly higher for both the GSA and TD groups, compared to the NE group (p<0.001), but MN frequencies were not elevated. Spearman correlation analysis showed that the frequency of MN was positively correlated with 8-OHdG. A positive correlation between DNA DI levels and 8-OHdG was also observed. In conclusion, our results indicated that low levels of occupational exposure to benzene and atmospheric pollutants may be linked to genotoxicity and oxidative DNA damage.