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Urinary frequency [keywords]
- Assay of lapatinib in murine models of cigarette smoke carcinogenesis. [JOURNAL ARTICLE]
- Carcinogenesis 2014 Jul 22.
Lapatinib, a dual tyrosine kinase inhibitor targeting the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER-2), is prescribed for the treatment of patients with metastatic breast cancer overexpressing HER-2. Involvement of this drug in pulmonary carcinogenesis has been poorly investigated. We used murine models suitable to evaluate cigarette smoke-related molecular and histopathological alterations. A total of 481 Swiss H mice were used. The mice were exposed to mainstream cigarette smoke (MCS) during the first 4 months of life. After 10 weeks, MCS caused an elevation of bulky DNA adducts, oxidative DNA damage, and an extensive downregulation of microRNAs in lung. After 4 months, an increase in micronucleus frequency was observed in peripheral blood erythrocytes. After 7.5 months, histopathological alterations were detected in the lung, also including benign tumors and malignant tumors, and in the urinary tract. A subchronic toxicity study assessed the nontoxic doses of lapatinib, administered daily with the diet after weaning. After 10 weeks, lapatinib significantly attenuated the MCS-related nucleotide changes and upregulated several low-intensity microRNAs in lung. The drug poorly affected the MCS systemic genotoxicity and had modest protective effects on MCS-induced preneoplastic lesions in lung and kidney, when administered under conditions that temporarily mimicked interventions either in current smokers or ex-smokers. On the other hand, it caused some toxicity to the liver. Thus, on the whole, lapatinib appears to have a low impact in the smoke-related lung carcinogenesis models used, especially in terms of tumorigenic response.
- Occurrence of Extended-Spectrum b-Lactamase Producers Among Enterobacteriaceae in a Paediatric Tertiary Care Facility in Kabul. [Journal Article]
- J Coll Physicians Surg Pak 2014 Jul; 24(7):530-1.
The aim of this study was to determine the occurrence of extended spectrum beta-lactamase (ESBL)-producing species of Enterobacteriaceae to control their spread, from March 2008 to June 2012. A total of 411 ESBL-producing isolates were reported belonging to the family Enterobacteriaceae. There were 235 (57.18%) hospital-acquired infections (HAIs) and 176 (42.82%) community-acquired infections (CAIs). Out of total isolates, majority were E. coli (n=165, 40.15%), followed by 38.93% Klebsiella spp. (n=161), 9.97% Enterobacter spp. (n=41) and 6.33% Serratia spp. (n=26). Amongst HAIs, most frequent i.e., 111/235 (47.23%) were Klebsiella spp, whereas, amongst CAIs, majority i.e., 96/176 (54.55%) were E. coli. The frequency of ESBL-producing isolates from different sites was blood (37.71%), urine (29.93%), respiratory tract (18.49%) and other sites including pus/pus swabs, CSF/body fluids and secretions (13.87%) respectively. Majority of blood stream infections were caused by ESBL-producing Klebsiella species which accounted for 55.48% of all cases who had septicaemia, whereas E. coli was responsible for causing majority of urinary tract infections (UTIs) and accounted for 78% of all UTIs cases. Intensive Care Unit (ICU) was the place where majority of infections (55%) were observed, followed by 29% in the Medical Unit and 16% in the Surgical Unit.
- Urinating Standing versus Sitting: Position Is of Influence in Men with Prostate Enlargement. A Systematic Review and Meta-Analysis. [JOURNAL ARTICLE]
- PLoS One 2014; 9(7):e101320.
It is suggested that the body posture during urination can influence urodynamic parameters in patients with Lower Urinary Tract Symptoms (LUTS) to an extent approaching pharmacological interventions. In this article, the influence of body position during micturition on maximum urinary flow rate (Qmax), voiding time (TQ) and post-void residual volume (PVR) in healthy males and patients with LUTS is analyzed by means of a systematic review and meta-analysis.A systematic search was conducted in 14 medical databases. Studies comparing urodynamic parameters in standing versus sitting position were eligible for inclusion. Studies were stratified according to health status of included male participants: healthy individuals and patients with LUTS. Standardized mean differences for Qmax, TQ and PVR were pooled in a random effects model.Eleven articles were included. In men with LUTS, a significantly lower PVR (-24.96 ml; 95%CI -48.70 to -1.23) was shown in sitting position compared to standing. In accordance, Qmax was increased (1.23 ml/s; 95%CI -1.02 to 3.48), and TQ was decreased (-0.62 s; 95%CI -1.66 to 0.42) in sitting position, although these differences did not reach statistical significance. In healthy men, Qmax (0.18 ml/s; 95% CI -1.67 to 2.02), TQ (0.49 s; 95%CI -3.30 to 4.27) and PVR (0.43 ml; 95%CI -0.79 to 1,65) were similar in sitting and standing position.For healthy men, no difference is found in any of the urodynamic parameters. In patients with LUTS, the sitting position is linked with an improved urodynamic profile.
- The effects of Ins2(Akita) diabetes and chronic angiotensin II infusion on cystometric properties in mice. [JOURNAL ARTICLE]
- Neurourol Urodyn 2013 Oct 28.
Diabetes is associated with both dysfunction of the lower urinary tract (LUT) and overactivity of the renin-angiotensin system (RAS). Although it is well known that the RAS affects normal LUT function, very little is known about RAS effects on the diabetic LUT. Accordingly, we investigated the effects of chronic angiotensin II (AngII) treatment on the LUT in a model of type 1 diabetes.Ins2(Akita) diabetic mice (20 weeks old) and their age-matched background controls underwent conscious cystometric evaluation after 4 weeks of chronic AngII treatment (700 ng/kg/min by osmotic pump) or vehicle (saline).Diabetic mice had compensated LUT function with bladder hypertrophy. Specifically, micturition volume, residual volume, and bladder capacity were all increased, while voiding efficiency and pressure generation were unchanged as bladder mass, contraction duration, and phasic urethral function were increased. AngII significantly increased voiding efficiency and peak voiding pressure and decreased phasic frequency irrespective of diabetic state and, in diabetic but not normoglycemic control mice, significantly decreased residual volume and increased contraction duration and nonphasic contraction duration.The Ins2(Akita) diabetic mice had compensated LUT function at 20 weeks of age. Even under these conditions, AngII had beneficial effects on LUT function, resulting in increased voiding efficiency. Future studies should therefore be conducted to determine whether AngII can rescue the decompensated LUT function occurring in end-stage diabetic uropathy. Neurourol. Urodynam. © 2013 Wiley Periodicals, Inc.
- Evaluating the results of stress urinary incontinence surgery with objective and subjective outcome measures. [JOURNAL ARTICLE]
- Eur J Obstet Gynecol Reprod Biol 2014 Jun 30.:68-71.
To assess the outcomes of stress urinary incontinence (SUI) surgery using objective and subjective measures in women with pure SUI and mixed urinary incontinence (MUI). The degree of correlation between the different outcome measures was also evaluated for both groups.A multicentre prospective cohort study of women who underwent surgery for SUI. A standardized cough stress test was used as the objective outcome measure, and specific items of the Epidemiology of Prolapse and Incontinence Questionnaire were used as the subjective outcome measure. The International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) and the Patient Global Impression of Improvement (PGI-I) questionnaires were used for global assessment. Kappa test was used to measure the degree of correlation between the outcome measures.The participants were categorized into two groups before surgery: pure SUI (n=116) and MUI (n=161). Six months after surgery, the cure rate of the SUI component was high in both groups according to the objective and subjective outcome measures. Global assessment showed lower cure rates. The degree of agreement between objective and subjective outcome measures was moderate (kappa 0.541, p<0.001) for women with pure SUI, and fair (kappa 0.377, p<0.001) for women with MUI. Correlation between the change in ICIQ-UI SF score (pre to post surgery) and the degree of satisfaction (PGI-I) was significant (p<0.01) for both the pure SUI group (0.43) and the MUI group (0.48).Both objective and subjective cure rates are high for women with pure SUI and MUI following SUI surgery in Spain. The degree of agreement between different outcome measures varies.
- Urinary Potassium Excretion and Risk of Developing Hypertension: The Prevention of Renal and Vascular End-Stage Disease Study. [JOURNAL ARTICLE]
- Hypertension 2014 Jul 21.
Previous prospective cohort studies on the association between potassium intake and risk of hypertension have almost exclusively relied on self-reported dietary data, whereas repeated 24-hour urine excretions, as estimate of dietary uptake, may provide a more objective and quantitative estimate of this association. Risk of hypertension (defined as blood pressure ≥140/90 mm Hg or initiation of blood pressure-lowering drugs) was prospectively studied in 5511 normotensive subjects aged 28 to 75 years not using blood pressure-lowering drugs at baseline of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study. Potassium excretion was measured in two 24-hour urine specimens at baseline (1997-1998) and midway during follow-up (2001-2003). Baseline median potassium excretion was 70 mmol/24 h (interquartile range, 57-85 mmol/24 h), which corresponds to a dietary potassium intake of ≈91 mmol/24 h. During a median follow-up of 7.6 years (interquartile range, 5.0-9.3 years), 1172 subjects developed hypertension. The lowest sex-specific tertile of potassium excretion (men: <68 mmol/24 h; women: <58 mmol/24 h) had an increased risk of hypertension after multivariable adjustment (hazard ratio, 1.20; 95% confidence interval, 1.05-1.37), compared with the upper 2 tertiles (Pnonlinearity=0.008). The proportion of hypertension attributable to low potassium excretion was 6.2% (95% confidence interval, 1.7%-10.9%). No association was found between the sodium to potassium excretion ratio and risk of hypertension after multivariable adjustment. Low urinary potassium excretion was associated with an increased risk of developing hypertension. Dietary strategies to increase potassium intake to the recommended level of 90 mmol/d may have the potential to reduce the incidence of hypertension.
- Bladder Instillation of Liposome Encapsulated OnabotulinumtoxinA Improves Overactive Bladder Symptoms- A Prospective Multi-center Double Blind Randomized Trial. [JOURNAL ARTICLE]
- J Urol 2014 Jul 18.
Cystoscopic intradetrusor injection of botulinum toxin has helped patients with refractory overactive bladder (OAB), but with increased risks of urinary tract infection and urinary retention. We assessed whether catheter instillation of onabotulinumtoxinA 200 U formulated with liposomes (lipo-BoNT) is safe and effective for the treatment of OAB.This two-center, double-blind, randomized, placebo-controlled study enrolled patients with OAB who were inadequately managed by antimuscarinics. Patients were assigned to intravesical instillation of lipo-BoNT (n=31) or normal saline (n=31). The primary end-point was the mean change in micturition events per three days at four weeks post-treatment. Additional end-points included mean changes of urgency event, frequency and urinary urge incontinence (UUI), as well as changes in OAB symptom scores (OABSS) and urgency severity scores (USS).At four weeks post-treatment, lipo-BoNT instillation was associated with a statistically significantly decrease in micturition events per three-days (-4.64 for lipo-BoNT versus -0.19 for placebo; p = 0.0252). Lipo-BoNT instillation was also associated with a statistically significant decrease in urinary urgency event with respect to baseline but not placebo. However, lipo-BoNT instillation was associated with a statistically significant decrease in USS scores versus those of placebo (p = 0.0181). These observed benefits of lipo-BoNT instillation were not accompanied by an increased risk of urinary retention. Effects of lipo-BoNT on UUI were inconclusive.A single intravesical instillation of lipo-BoNT was associated with decreases of OAB symptoms without side effects. Intravesical instillation of liposomal botulinum toxin may be a promising approach for treatment of refractory OAB.
- The Risk of Urinary Tract Infection after Flexible Cystoscopy in Bladder Tumor Patients who did not receive Prophylactic Antibiotics. [JOURNAL ARTICLE]
- J Urol 2014 Jul 18.
To determine the frequency of febrile urinary tract infection (UTI) after outpatient flexible cystoscopy in antibiotic-naïve bladder tumor patients.A total of 3108 outpatient cystoscopies were performed in 1110 bladder tumor patients. Immediately before undergoing cystoscopy, they submitted a voided urine sample for culture. Significant bacteriuria was defined as >10(4) CFU/ml with a single organism. The patients received no antibiotics immediately before or after cystoscopy. They were followed 30 days for onset of febrile UTI.Of the 3108 patient-cystoscopies, 673 (22%) had asymptomatic bacteriuria, and 2435 (78%) had sterile urine. Fifty-nine patients (1.9%) developed febrile UTI within 30 days of cystoscopy; 3.7% in infected, and 1.4% in uninfected patients (P=.01). All resolved within 12-24 hours with oral antibiotics. None of the patients was admitted for bacterial sepsis.Antibacterial therapy before outpatient flexible cystoscopy does not appear necessary in patients who have no clinical signs or symptoms of acute urinary tract infection, including presence of bacteriuria.
- Clinical equivalence of budesonide dry powder inhaler and pressurized metered dose inhaler. [JOURNAL ARTICLE]
- Clin Respir J 2014 Jul 11.
A delivery device is the most important factor that determines the local/systemic bioavailability of inhaled corticosteroids. Dry powder inhalers (DPIs) and pressurized metered dose inhalers (pMDIs) are the most commonly used delivery devices for localized drug delivery to the airways.This study was to compare the clinical equivalence of budesonide delivered by the Pulmicort Turbuhaler(TM) (DPI) and the Aeronide(TM) inhaler (pMDI).The two inhalers were compared for their pharmaceutical equivalence and clinical equivalence. The in vitro test included the uniformity of the delivered dose and determination of the aerodynamic particle size of budesonide. The in vivo test was carried out in 36 patients with mild to moderate asthma. This was a randomized single-blinded study conducted for a period of three months. This included assessment of the spirometric parameters (FEV1, FVC, PEFR, FEF25-75 ), the severity of asthma symptoms, adverse events, frequency of short acting inhaled bronchodilator usage and measurement of urinary cortisol levels.The aerodynamic particle size was slightly different between the two inhalers (2.3±0.2 μm for Pulmicort Turbuhaler(TM) and 2.2±0.2 μm for Aeronide(TM) inhaler). Both inhalers passed the uniformity of delivered dose (95.4 and 97.4%) specified in the British Pharmacopoeia. There was no statistically significant difference observed between the two inhalers in terms of the spirometric parameters, symptom free days, frequency of bronchodilator usage and the level of urinary cortisol.In addition to pharmaceutical equivalence, no clinical difference observed between the two budesonide inhalers.
- High frequency of. [JOURNAL ARTICLE]
- J Hematol Oncol 2014 Jul 20; 7(1):47.
TERT promoter mutations were recently discovered in melanoma by next generation sequencing. Subsequently, several malignancies including urothelial carcinoma were also found to be associated with the same TERT promoter mutations. Small cell carcinoma (SCC) of the urinary bladder is a rare subtype with an aggressive clinical course. Despite the frequent occurrence of TERT promoter mutations in urothelial carcinoma, the incidence of the mutations in SCC of the urinary bladder is unknown. In addition, as a potential molecular marker to distinguish SCC of the urinary bladder from SCC of the prostate, lung (SCLC) and other origins, this information may be clinically useful. We collected a total of 11 cases of SCC of the urinary bladder (10 cases are primary SCC of the urinary bladder; 1 case has primary SCC of the urinary bladder and liver metastasis). We also included 20 cases of SCLC, 2 cases of SCC of the prostate, 5 cases of Merkel cell carcinoma, and 6 cases of SCC from other sites (cervical, GE junction, breast, and soft tissue). In addition, 3 cases of non-neoplastic tissue from the matched SCC of bladder patient and 14 cases of benign urinary bladder were also included. All tumor sections have been examined to confirm the diagnosis and to make sure more than 20% are of tumor content. Genomic DNA was isolated from FFPE tissue and a fragment of the TERT promoter (145 bp) was amplified by PCR. The TERT promoter mutations are determined by bi-directional Sanger sequencing. All (11/11) SCC of the urinary bladder bear TERT promoter mutation C228T. Neither of SCC from all other origins nor matched non-neoplastic tissue contains the TERT promoter mutations. We demonstrated a high frequency TERT promoter mutation in SCC of the urinary bladder, but not in SCC of other origin, such as the prostate. The findings further illustrate molecular differences between SCC of the urinary bladder and SCC of other origins, despite their shared morphologic and immunophenotypic similarities. The TERT promoter mutation may be a biomarker differentiating SCC of the urinary bladder from SCC of other origins.