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American Journal of Veterinary Research May 2006To compare the urodynamic and morphologic effects of the administration of estriol alone and in combination with phenylpropanolamine on the lower portion of the... (Clinical Trial)
Clinical Trial
Urodynamic and morphologic changes in the lower portion of the urogenital tract after administration of estriol alone and in combination with phenylpropanolamine in sexually intact and spayed female dogs.
OBJECTIVE
To compare the urodynamic and morphologic effects of the administration of estriol alone and in combination with phenylpropanolamine on the lower portion of the urogenital tract in female dogs.
ANIMALS
3 sexually intact and 3 spayed female Beagles without urinary incontinence.
PROCEDURE
Dogs received estriol (2 mg, PO) once daily for 7 days followed by estriol (2 mg, PO) and phenylpropanolamine (1.5 mg/kg, PO) once daily for 7 days. Urethral pressure profilometry, diuresis cystometry, and vaginourethrography were performed before treatment (day 0) and at days 7 and 14. The maximum urethral pressure (MUP) and closure pressure (MUCP), urethral functional and anatomic profile lengths, integrated pressure (IP), plateau, distance before MUP, maximum meatus pressure, threshold pressure, threshold volume, compliance, urethral length, and vaginal length and width were measured.
RESULTS
Before treatment, no urodynamic differences were observed between the 2 groups; however, vaginal length and width were significantly shorter in spayed dogs. Compared with day 0 values, estriol treatment significantly increased MUP, MUCP, and IP values at day 7, but at day 14, this effect decreased despite phenylpropanolamine administration. No morphologic changes from baseline were detected after either treatment in any dog.
CONCLUSIONS AND CLINICAL RELEVANCE
Data suggest that estriol mainly acts on the urethral sphincter mechanism by increasing urethral resistance in sexually intact and spayed female dogs without urinary incontinence. Administration of estriol and phenylpropanolamine did not increase the urethral resistance more than estriol alone. The urodynamic effects of estriol in female dogs with urinary incontinence remain to be elucidated.
Topics: Animals; Dogs; Drug Therapy, Combination; Estriol; Female; Hysterectomy; Ovariectomy; Phenylpropanolamine; Sympathomimetics; Urodynamics; Urogenital System
PubMed: 16649928
DOI: 10.2460/ajvr.67.5.901 -
Emergency Medicine Journal : EMJ Mar 2017
Review
Topics: Blood Pressure; Emergency Service, Hospital; Humans; Hypotension; Infusions, Intravenous; Metaraminol; Sepsis; Vasoconstrictor Agents
PubMed: 28232631
DOI: 10.1136/emermed-2017-206590.3 -
BMC Urology Oct 2014Overactive 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... (Review)
Review
BACKGROUND
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.
METHODS
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.
RESULTS
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 α-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.
CONCLUSION
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.
Topics: Adrenergic alpha-Antagonists; Benzhydryl Compounds; Constipation; Cresols; Delayed-Action Preparations; Drug Therapy, Combination; Humans; Lower Urinary Tract Symptoms; Male; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents; Xerostomia
PubMed: 25348235
DOI: 10.1186/1471-2490-14-84 -
The Cochrane Database of Systematic... Oct 2021Most people who stop smoking gain weight. This can discourage some people from making a quit attempt and risks offsetting some, but not all, of the health advantages of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Most people who stop smoking gain weight. This can discourage some people from making a quit attempt and risks offsetting some, but not all, of the health advantages of quitting. Interventions to prevent weight gain could improve health outcomes, but there is a concern that they may undermine quitting.
OBJECTIVES
To systematically review the effects of: (1) interventions targeting post-cessation weight gain on weight change and smoking cessation (referred to as 'Part 1') and (2) interventions designed to aid smoking cessation that plausibly affect post-cessation weight gain (referred to as 'Part 2').
SEARCH METHODS
Part 1 - We searched the Cochrane Tobacco Addiction Group's Specialized Register and CENTRAL; latest search 16 October 2020. Part 2 - We searched included studies in the following 'parent' Cochrane reviews: nicotine replacement therapy (NRT), antidepressants, nicotine receptor partial agonists, e-cigarettes, and exercise interventions for smoking cessation published in Issue 10, 2020 of the Cochrane Library. We updated register searches for the review of nicotine receptor partial agonists.
SELECTION CRITERIA
Part 1 - trials of interventions that targeted post-cessation weight gain and had measured weight at any follow-up point or smoking cessation, or both, six or more months after quit day. Part 2 - trials included in the selected parent Cochrane reviews reporting weight change at any time point.
DATA COLLECTION AND ANALYSIS
Screening and data extraction followed standard Cochrane methods. Change in weight was expressed as difference in weight change from baseline to follow-up between trial arms and was reported only in people abstinent from smoking. Abstinence from smoking was expressed as a risk ratio (RR). Where appropriate, we performed meta-analysis using the inverse variance method for weight, and Mantel-Haenszel method for smoking.
MAIN RESULTS
Part 1: We include 37 completed studies; 21 are new to this update. We judged five studies to be at low risk of bias, 17 to be at unclear risk and the remainder at high risk. An intermittent very low calorie diet (VLCD) comprising full meal replacement provided free of charge and accompanied by intensive dietitian support significantly reduced weight gain at end of treatment compared with education on how to avoid weight gain (mean difference (MD) -3.70 kg, 95% confidence interval (CI) -4.82 to -2.58; 1 study, 121 participants), but there was no evidence of benefit at 12 months (MD -1.30 kg, 95% CI -3.49 to 0.89; 1 study, 62 participants). The VLCD increased the chances of abstinence at 12 months (RR 1.73, 95% CI 1.10 to 2.73; 1 study, 287 participants). However, a second study found that no-one completed the VLCD intervention or achieved abstinence. Interventions aimed at increasing acceptance of weight gain reported mixed effects at end of treatment, 6 months and 12 months with confidence intervals including both increases and decreases in weight gain compared with no advice or health education. Due to high heterogeneity, we did not combine the data. These interventions increased quit rates at 6 months (RR 1.42, 95% CI 1.03 to 1.96; 4 studies, 619 participants; I = 21%), but there was no evidence at 12 months (RR 1.25, 95% CI 0.76 to 2.06; 2 studies, 496 participants; I = 26%). Some pharmacological interventions tested for limiting post-cessation weight gain (PCWG) reduced weight gain at the end of treatment (dexfenfluramine, phenylpropanolamine, naltrexone). The effects of ephedrine and caffeine combined, lorcaserin, and chromium were too imprecise to give useful estimates of treatment effects. There was very low-certainty evidence that personalized weight management support reduced weight gain at end of treatment (MD -1.11 kg, 95% CI -1.93 to -0.29; 3 studies, 121 participants; I = 0%), but no evidence in the longer-term 12 months (MD -0.44 kg, 95% CI -2.34 to 1.46; 4 studies, 530 participants; I = 41%). There was low to very low-certainty evidence that detailed weight management education without personalized assessment, planning and feedback did not reduce weight gain and may have reduced smoking cessation rates (12 months: MD -0.21 kg, 95% CI -2.28 to 1.86; 2 studies, 61 participants; I = 0%; RR for smoking cessation 0.66, 95% CI 0.48 to 0.90; 2 studies, 522 participants; I = 0%). Part 2: We include 83 completed studies, 27 of which are new to this update. There was low certainty that exercise interventions led to minimal or no weight reduction compared with standard care at end of treatment (MD -0.25 kg, 95% CI -0.78 to 0.29; 4 studies, 404 participants; I = 0%). However, weight was reduced at 12 months (MD -2.07 kg, 95% CI -3.78 to -0.36; 3 studies, 182 participants; I = 0%). Both bupropion and fluoxetine limited weight gain at end of treatment (bupropion MD -1.01 kg, 95% CI -1.35 to -0.67; 10 studies, 1098 participants; I = 3%); (fluoxetine MD -1.01 kg, 95% CI -1.49 to -0.53; 2 studies, 144 participants; I = 38%; low- and very low-certainty evidence, respectively). There was no evidence of benefit at 12 months for bupropion, but estimates were imprecise (bupropion MD -0.26 kg, 95% CI -1.31 to 0.78; 7 studies, 471 participants; I = 0%). No studies of fluoxetine provided data at 12 months. There was moderate-certainty that NRT reduced weight at end of treatment (MD -0.52 kg, 95% CI -0.99 to -0.05; 21 studies, 2784 participants; I = 81%) and moderate-certainty that the effect may be similar at 12 months (MD -0.37 kg, 95% CI -0.86 to 0.11; 17 studies, 1463 participants; I = 0%), although the estimates are too imprecise to assess long-term benefit. There was mixed evidence of the effect of varenicline on weight, with high-certainty evidence that weight change was very modestly lower at the end of treatment (MD -0.23 kg, 95% CI -0.53 to 0.06; 14 studies, 2566 participants; I = 32%); a low-certainty estimate gave an imprecise estimate of higher weight at 12 months (MD 1.05 kg, 95% CI -0.58 to 2.69; 3 studies, 237 participants; I = 0%).
AUTHORS' CONCLUSIONS
Overall, there is no intervention for which there is moderate certainty of a clinically useful effect on long-term weight gain. There is also no moderate- or high-certainty evidence that interventions designed to limit weight gain reduce the chances of people achieving abstinence from smoking.
Topics: Electronic Nicotine Delivery Systems; Humans; Nicotine; Smoking Cessation; Tobacco Use Cessation Devices; Weight Gain
PubMed: 34611902
DOI: 10.1002/14651858.CD006219.pub4 -
Tidsskrift For Den Norske Laegeforening... Mar 2005Sales of herbal dietary supplements have increased dramatically. A patient case drew our attention to the problem of incomplete declaration of content.
BACKGROUND
Sales of herbal dietary supplements have increased dramatically. A patient case drew our attention to the problem of incomplete declaration of content.
METHODS
Two dietary supplements which the manufacturers claim to be natural, extremely fat-burning and energizing were analysed, as were urine and serum samples from persons taking these supplements.
RESULTS
Surprisingly, the herbal dietary supplements contained drugs. Diazepam, clonazepam, ephedrine and metabolites were found when analyzing serum samples after intake of the dietary supplement Thermo-X 650, ephedrine and phenylpropanolamine after intake of the Purple Burn supplement.
INTERPRETATION
Use of herbal dietary supplement can have serious consequences, for instance through interactions with drug therapy. Consumers must be given sufficient product information for safe use.
Topics: Adult; Clonazepam; Diazepam; Dietary Supplements; Drug Interactions; Ephedrine; Female; Humans; Plant Extracts; Risk Factors
PubMed: 15776071
DOI: No ID Found -
Annals of Internal Medicine Mar 2008Urinary incontinence in women is a common problem that adversely affects quality of life. (Review)
Review
BACKGROUND
Urinary incontinence in women is a common problem that adversely affects quality of life.
PURPOSE
To synthesize evidence of management of urinary incontinence in women.
DATA SOURCES
MEDLINE, CINAHL, and the Cochrane Library.
STUDY SELECTION
96 randomized, controlled trials (RCTs) and 3 systematic reviews published in English from 1990 through May 2007.
DATA EXTRACTION
Using standardized protocols, reviewers abstracted cases of continence, improvement of urinary incontinence, and prevalence of urinary incontinence to calculate risk difference.
DATA SYNTHESIS
Compared with regular care, pelvic floor muscle training plus bladder training resolved urinary incontinence (pooled risk difference, 0.13 [95% CI, 0.07 to 0.20]). Pelvic floor muscle training alone resolved or improved urinary incontinence compared with regular care, although the effect size was inconsistent across studies. Different injectable bulking agents and medical devices were associated with similar continence and improvement rates. Electrical stimulation failed to resolve urinary incontinence. Oral hormone administration increased rates of urinary incontinence compared with placebo in most RCTs (1243 women). Transdermal or vaginal estrogen resulted in inconsistent improvement of urinary incontinence. Adrenergic drugs did not resolve or improve urinary incontinence. Oxybutynin or tolterodine resolved urinary incontinence compared with placebo (pooled risk difference, 0.18 [CI, 0.13 to 0.22]). Duloxetine compared with placebo improved (pooled risk difference, 0.11 [CI, 0.07 to 0.14]) but did not resolve urinary incontinence, with no significant dose-response association.
LIMITATIONS
Inconsistent measurements of outcomes limited the findings. Predictors of better effect have not been identified in RCTs.
CONCLUSION
Moderate levels of evidence suggest that pelvic floor muscle training and bladder training resolved urinary incontinence in women. Anticholinergic drugs resolved urinary incontinence, with similar effects from oxybutynin or tolterodine. Duloxetine improved but did not resolve urinary incontinence. The effects of electrostimulation, medical devices, injectable bulking agents, and local estrogen therapy were inconsistent.
Topics: Benzhydryl Compounds; Cholinergic Antagonists; Collagen; Cresols; Duloxetine Hydrochloride; Electric Stimulation Therapy; Estrogen Replacement Therapy; Exercise Therapy; Female; Humans; Magnetics; Mandelic Acids; Pelvic Floor; Pessaries; Phenylpropanolamine; Randomized Controlled Trials as Topic; Thiophenes; Tolterodine Tartrate; Urinary Incontinence
PubMed: 18268288
DOI: 10.7326/0003-4819-148-6-200803180-00211 -
American Journal of Epidemiology Jul 2013Previous studies suggested that early pregnancy exposure to specific oral decongestants increases the risks of several birth defects. Using January 1993-January 2010...
Previous studies suggested that early pregnancy exposure to specific oral decongestants increases the risks of several birth defects. Using January 1993-January 2010 data from the Slone Epidemiology Center Birth Defects Study, we tested those hypotheses among 12,734 infants with malformations (cases) and 7,606 nonmalformed control infants in the United States and Canada. Adjusted odds ratios and 95% confidence intervals were estimated for specific birth defects, with controlling for potential confounders. Findings did not replicate several hypotheses but did support 3 previously reported associations: phenylephrine and endocardial cushion defect (odds ratio = 8.0; 95% confidence interval: 2.5, 25.3; 4 exposed cases), phenylpropanolamine and ear defects (odds ratio = 7.8; 95% confidence interval: 2.2, 27.2; 4 exposed cases), and phenylpropanolamine and pyloric stenosis (odds ratio = 3.2; 95% confidence interval: 1.1, 8.8; 6 exposed cases). Hypothesis-generating analyses involving multiple comparisons identified a small number of associations with oral and intranasal decongestants. Accumulating evidence supports associations between first-trimester use of specific oral and possibly intranasal decongestants and the risk of some infrequent specific birth defects.
Topics: Abnormalities, Drug-Induced; Administration, Intranasal; Administration, Oral; Adult; Canada; Case-Control Studies; Female; Humans; Infant, Newborn; Logistic Models; Nasal Decongestants; Nonprescription Drugs; Odds Ratio; Pregnancy; Pregnancy Trimester, First; Self Report; United States
PubMed: 23825167
DOI: 10.1093/aje/kws427 -
Yakugaku Zasshi : Journal of the... Feb 2009A randomized, double-blind, placebo- and active comparator-controlled study was conducted in 69 centers to compare detrusitol and oxybutynin with placebo in Japanese and... (Review)
Review
A randomized, double-blind, placebo- and active comparator-controlled study was conducted in 69 centers to compare detrusitol and oxybutynin with placebo in Japanese and Korean patients with an overactive bladder (OAB). Detrusitol had similar efficacy but was better tolerated than oxybutynin in Japanese and Korean patients with OAB. The study result was acknowledged as pivotal data in the clinical data package when NDA was filed and successfully approved both in Japan and Korea. Some differences were found in the efficacy and safety of the drug between the Japanese and Korean data, though. We therefore investigated the differences through stratified analysis; however exact causes could not be identified. This study is positioned as a first multinational clinical trial conducted in East Asia. From the aspects of utilization of interoperable data obtained from such multinational clinical trials for NDA filing and earliest possible registration of drugs in the participating countries, we believe it is important to accumulate more experiences in conducting multinational clinical trials. At this time, it is our prime task to minimize the "drug lag" in Japan; I think improving the speed of clinical trials is one of the factors to solve the issue. Global clinical trials involving Western and Asian countries make it possible to use the study data effectively and commonly in many countries. Moreover, from the viewpoint of revitalization of clinical trials, conducting global clinical trials is critically important; so we intend to continue accumulation of our experiences in global clinical trials.
Topics: Benzhydryl Compounds; Cresols; Double-Blind Method; Female; Humans; International Cooperation; Japan; Korea; Male; Mandelic Acids; Multicenter Studies as Topic; Muscarinic Antagonists; Phenylpropanolamine; Randomized Controlled Trials as Topic; Tolterodine Tartrate; Urinary Bladder, Overactive
PubMed: 19182454
DOI: 10.1248/yakushi.129.241 -
Journal of Ethnopharmacology Dec 2010Although there is a rich body of research available regarding the effect of acute and chronic khat dosing in animal models, research on the behavioral and cognitive... (Review)
Review
Although there is a rich body of research available regarding the effect of acute and chronic khat dosing in animal models, research on the behavioral and cognitive effects of khat in human subjects is not extensive and several of the available studies have been done only in the context of observational and single-case studies. In light of the absence of a substantial literature on the neurobehavioral deficits associated with khat use and to provide a context that could be used to identify themes for future research we review previous research that has focused on other stimulant drugs. This review highlights multiple areas of neurocognitive deficit that have been identified in previous studies of individuals who have been chronic users of stimulants, such as amphetamines and methamphetamines. The review highlights a substantial body of evidence demonstrating a wide range of learning and memory impairments including deficits that persist during abstinence from active drug use. This review does not imply a similar khat effect, but due to some similarities pharmacologically between the active components of khat (cathinone and cathine) and amphetamines, future studies examining these same domains of cognitive functioning in chronic khat users and abstinent khat users appears to be warranted, if possible using some of the same or similar laboratory measures.
Topics: Alkaloids; Amphetamines; Catha; Central Nervous System Stimulants; Cognition; Humans; Phenylpropanolamine; Plant Leaves; Psychotropic Drugs; Substance Withdrawal Syndrome; Substance-Related Disorders
PubMed: 20553832
DOI: 10.1016/j.jep.2010.05.033 -
Chinese Medical Journal Aug 2017Whether cholinergic innervations and/or autophagy have a role in the etiopathology of benign prostatic hyperplasia (BPH) is still unknown. This study aimed to...
BACKGROUND
Whether cholinergic innervations and/or autophagy have a role in the etiopathology of benign prostatic hyperplasia (BPH) is still unknown. This study aimed to investigate the role of cholinergic innervation and autophagy in the etiopathology of BPH.
METHODS
Male, 13-week-old spontaneous hypertension rats (spontaneous BPH animal model) were divided into three groups: an experimental group (EG, n = 24), a control group (CG, n = 24), and a normal control group (NC, n = 10). The EG animals were intragastrically injected with tolterodine (3.5 mg/kg, twice a day), CG animals were intragastrically injected with physiological saline, and the NC animals did not receive any treatment. Rats were sacrificed every 4 weeks, and the prostatic gross morphological changes, wet weight/body weight (ww/bw), dry weight/wet weight (dw/ww), histological changes, ultrastructural changes, and LC3 immunohistochemistry were continuously observed and compared.
RESULTS
The gross morphological and ww/bw changes in the three groups were similar at every stage. The dw/ww (mg/mg) values of the EG at week 17, 21, 25, and 29 were 0.1478 ± 0.0034, 0.1653 ± 0.0036, 0.1668 ± 0.0045, and 0.1755 ± 0.0034, respectively, and the CG values were 0.1511 ± 0.0029, 0.1734 ± 0.0020, 0.1837 ± 0.0052, and 0.1968 ± 0.0045, respectively. The difference between EG and CG for dw/ww showed statistical significance after 21 weeks of age (week 21: P= 0.016, week 25: P= 0.008, and week 29: P= 0.001). Both EG and CG, prostatic glandular epithelial cell proliferation, and secretory function improved with age, but in EG, these improvements were slower than those in CG, and all the differences were statistically significant after 21 weeks. An increasing number of autophagosomes in the prostatic glandular cell cytoplasm, attenuation of LC3-I immunohistochemical staining, enhancement of LC3-II staining, and the ratio of LC3-II/LC3-I staining were all progressive in both groups, but the rate of change in EG was faster than that in CG, and these differences gained statistical significance after 25 weeks. Comparisons with regard to the above indexes between CG and NC showed no statistical significance at any stage.
CONCLUSIONS
Cholinergic innervations and activation of autophagy appear to have important functions in the etiopathology of BPH. Drug-mediated blockade of cholinergic innervations could delay the physiopathology processes. Moreover, overactivation of autophagy may also play an important role in this delay.
Topics: Animals; Autophagy; Body Weight; Cell Proliferation; Disease Models, Animal; Immunohistochemistry; Male; Prostate; Prostatic Hyperplasia; Rats; Tolterodine Tartrate
PubMed: 28776548
DOI: 10.4103/0366-6999.211877