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Objective To evaluate voiding behavior characteristics in intact and sham mice, and to examine whether intact mice show changes in "normal" micturition with aging. Methods A total of 72 8-week-old mice were divided into two groups - intact and sham - and the latter group was subjected to a sham of partial bladder outlet obstruction surgery. Urination frequency was evaluated (through metabolic cages) at 1, 2, 3, 6 and 12 months after the surgery (or at the equivalent time points for the intact mice). To address possible mechanisms for aging and surgical effects on urinary behavior, quantitative real-time polymerase chain reaction assays were carried out. Primary data were evaluated using scatter plots and descriptive statistics. Results In sham mice, urination frequency showed strong variation at the earlier post-surgical time points (especially at 1 month), with variation decreasing with time. Quantitative real-time polymerase chain reaction showed that the serotonin 2C receptor-encoding mRNA accumulated to >28-fold higher levels at 24 months compared with 3 months in intact mice. A major limitation of the quantitative real-time polymerase chain reaction experiments was that we did not separate whole bladder into muscle and mucosa. Conclusions Although a sham operation is typically used in partial bladder outlet obstruction experiments to provide control animals, the sham group might itself show increased variation in micturition frequency at early times after surgery, compared with intact animals.

Pendahuluan: Masa postpartum sangat penting, karena sering terjadinya komplikasi antara lain infeksi genetalia. Beberapa faktor penyebab terjadinya infeksi adalah kurang nutrisi, kurang menjaga kebersihan diri atau perineum, kurang istirahat, kurang mobilisasi dan olah raga serta karena peningkatan frekuensi berkemih yang dapat menimbulkan infeksi di sekitar genetalia. Tujuan penelitian: ini adalah untuk menganalisis bagaimana pengaruh latihan kegel terhadap frekuensi BAK pada ibu postpartum di Praktik Mandiri Bidan Husniyati Palembang. Metode penelitian: ini adalah quasi eksperimen dengan disain post test only non equivalent control group yaitu pengukuran dilakukan setelah kelompok intervensi diberikan perlakuan, kemudian hasil pengukuran atau observasi dibandingkan dengan hasil observasi pada kelompok kontrol, dengan variabel terikat adalah frekuensi BAK dan variabel bebas adalah latihan kegel. Sampel penelitian diambil menggunakan teknik purposive sampling, terdiri dari 30 ibu postpartum yang dibagi dalam 2 kelompok: kelompok latihan kegel; kelompok kontrol. Analisis yang digunakan adalah analisis univariat dan bivariat. Hasil penelitian: dari hasil uji statistik Kendall’s tau, tidak ada pengaruh latihan kegel terhadap frekuensi berkemih ibu postpartum di PMB Husniyati Kota Palembang dimana p value 0,063 (> 0,05). The postpartum period is very important, because frequent complications include genetal infection. Some of the factors causing infection are lack of nutrition, lack of personal hygiene or perineum, lack of rest, lack of mobilization and exercise as well as due to increased frequency of urination which can cause infection around genetalia. The purpose of this study was to analyze how the effect of Kegel exercises on the urinate frequency in postpartum mothers in the PMB Husniyati Palembang. The method in this study is a quasi-experimental design with a post-test only non-equivalent control group that is the measurement carried out after the intervention group is given treatment, then the measurement or observation results are compared with the results of observations in thecontrol group, with the dependent variable being the frequency of BAK and the independent variable is the kegel exercise. The research sample was taken using a purposive sampling technique, consisting of 30 postpartum mothers divided into 2 groups: the kegel exercise group; control group. The analysis used is univariate and bivariate analysis. The results of Kendall's statistical test results know, there is no effect of Kegel exercises on the urinate frequency of postpartum maternal at PMB Husniyati Palembang where p value is 0.063 (> 0.05).

We present the results of botulinum toxin type A (BT-A) treatment in 49 women (aged 41-65 years) with bladder pain syndrome. Previously, all patients underwent oral and intravesical drug therapy in addition to hydrodistention of the bladder without significant clinical effect. BT-A at a dose of 100 U (20 points at 5 units) was injected into the bladder under general anesthesia. Treatment results were evaluated 3 months after the treatment using specialized questionnaires such as the Pelvic Pain and Urgency/Frequency (PUF) Scale, O’Leary-Sant Symptom Index and Interstitial Cystitis Scale, visual analogue pain scale (VAS), and urinary diaries. Remarkably, the treatment was effective in 46 (93.8%) patients. By the end of the third month after the BT-A injection, the PUF Scale score, the O’Leary-Sant Symptom and Interstitial Cystitis Scale, and VAS reduced by 41.3%, 32%, and 34%, respectively, and urination frequency decreased by 38.5%. Thus, BT-A is an effective method for treating bladder pain syndrome in patients who are refractory to other treatment methods. (For citation: Al-Shukri SH, Kuzmin IV, Slesarevskaya MN, Ignashov YuA. Botulinum toxin type A in the treatment of bladder pain syndrome in women: initial results. Urologicheskie vedomosti. 2018;8(2):5-10. doi: 10.17816/uroved825-10).

[Purpose] To clarify factors contributing to habituation of pelvic floor muscle training (PFMT) for urinary incontinence. [Subjects and Methods] We included 13 healthy females and examined diurnal and nocturnal urination frequency at initial program participation and at 3 months. The survey used the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), a 10-level self-assessment of anxiety associated with urinary incontinence, and a 10-level self-evaluation of PFMT understanding and skill acquisition. We evaluated PFMT practice at home and postures that facilitated PFMT. The practice of PFMT at home was surveyed during a 3-month period. [Results] Compared to baseline, the level of skill acquisition assessed by the ICIQ-SF and PFMT according to the 10-level self-evaluation improved significantly at 3 months. The rate of PFMT sessions performed at home per week was high. The number of times PFMT was performed per day was positively correlated with level of understanding and acquisition of skills pertaining to PFMT, according to the 10-level self-assessment. [Conclusion] By incorporating behavior modification techniques appropriate for urinary incontinence and by increasing the level of understanding regarding incontinence and PFMT, as well as the level of skill acquisition, self-efficacy increased. This may have motivated habituation of PFMT.

Background Urinary disorders in cats often require subjective caregiver quantification of clinical signs to establish a diagnosis and monitor therapeutic outcomes. Objective To investigate use of a video recording system (VRS) to better assess and quantify urination behaviors in cats. Animals Eleven healthy cats and 8 cats with disorders potentially associated with abnormal urination patterns. Methods Prospective study design. Litter box urination behaviors were quantified with a VRS for 14 days and compared to daily caregiver observations. Video recordings were analyzed by a behavior analysis software program. Results The mean number of urinations per day detected by VRS (2.5 ± 0.7) was significantly higher compared with caregiver observations (0.6 ± 0.6; P < .0001). Five cats were never observed in the litter box by their caregivers. The mean number of urinations per day detected by VRS was significantly higher for abnormal cats (2.9 ± 0.7) compared with healthy cats (2.1 ± 0.7; P = .02); there were no apparent differences in frequency between these groups reported by caregivers (0.7 ± 1.0 and 0.5 ± 1.0, respectively). There were no differences in mean urination time between healthy and abnormal cats as determined by VRS or caregivers. Mean cover-up time determined by VRS was significantly longer in healthy cats (22.7 ± 12.9 seconds/urination) compared with abnormal cats (8.7 ± 12.9 seconds/urination; P = .03); differences in cover-up time were not detected by caregivers. Conclusions and Clinical Importance Caregivers commonly underestimate urination frequency in cats when compared to video-based observations. Video recording appears to facilitate objective assessment of urination behaviors and could be of value in future clinical studies of urinary disorders in cats.

Diuretics is a substance that can stimulate of urine output. The content of flavonoid compunds contained in water extracts of avocado leaves have a diuretic activity. Testing is done withgiving a water extract of avocado leaves per oral to 30 male rats strain (Sparague-Dawley) with weight 200 grams were divided into 6 groups. Frequency of urination with water extract of avocado leaves 5 % , 10 % , 15 % and 20 % respectively which is 2 , 5 , 9 and 20 times with observation for 3 hours. Furosemide tablets urination frequency was 25 times over 3 hours. The result showed that the water extract of avocado leaves 20% have diuretic activity is equivalent to Furosemide tablets at a dose of 7.2 mg / 200 mg BB in male rats.

Objective: The present study assessed the relationship between nocturia and cue-induced urinary urges.Methods: Three hundred and six participants (201 females) ranging from 24 to 88 years of age, median age 53 years old participated in an online survey about bladder symptoms and cues related to urinary urge and urgency incontinence.Results: We found that individuals who experience more instances of cue-related urges have more nocturnal urination, F (4. 504) = 3.106, p < .001, when controlling for age, day time urination frequency, and gender. Our findings suggest that awakening from sleep may be the cause rather than the consequence of urinary urgency.Conclusion: These results add to previous research by offering support that psychological contributors are primary or secondary predictors of urological disorders.

La asociación entre los órganos genitales y urinarios ha sido establecida desde hace muchos años. El papiro de Kahum, escrito en el antiguo Egipto 2000 años AC se dedica exclusivamente a las enfermedades de la mujer. En ese documento, las enfermedades de los órganos genitales femeninos son consideradas en conjunto con las enfermedades de la vejiga. En la sección 67 del papiro de Ebers, escrito 1500 años AC se describe las alteraciones de la micción con relación a su frecuencia, retención y la "quemazón"; así como el "tratamiento de la mujer que sufre enfermedades de su orina y útero". En la sección 24 de este mismo papiro se describe alteraciones ginecológicas y obstétricas, y contiene prescripciones sobre el tratamiento de las úlceras y de la inflamación de la vulva, del prolapso, de la esterilidad y de las menorragias, asimismo prescripciones sobre alteraciones de las vías urinarias.

BACKGROUND The main source of nitrogen (N) leaching from grazed pastures is animal urine with a high N deposition rate (i.e. per urine patch), particularly between late summer and early winter. Salt is a potential mitigation option as a diuretic to induce greater drinking-water intake, increase urination frequency, decrease urine N concentration and urine N deposition rate, and thereby potentially decrease N leaching. This hypothesis was tested in three phases: a cattle metabolism stall study to examine effects of salt supplementation rate on water consumption, urination frequency and urine N concentration; a grazing trial to assess effects of salt (150 g per heifer per day) on urination frequency; and a lysimeter study on effects of urine N rate on N leaching. RESULTS Salt supplementation increased cattle water intake. Urination frequency increased by up to 69%, with a similar decrease in urine N deposition rate and no change in individual urination volume. Under field grazing, sensors showed increased urination frequency by 17%. Lysimeter studies showed a proportionally greater decrease in N leaching with decreased urine N rate. Modelling revealed that this could decrease per-hectare N leaching by 10–22%. CONCLUSIONS Salt supplementation increases cattle water intake and urination frequency, resulting in a lower urine N deposition rate and proportionally greater decrease in urine N leaching. Strategic salt supplementation in autumn/early winter with feed is a practical mitigation option to decrease N leaching in grazed pastures. © 2015 Society of Chemical Industry

WOS: 000384827400006, PubMed: 27621918, Introduction: Eosinophilic cystitis (EC) is a rare and poorly understood inflammatory condition, characterized by eosinophilic infiltration of all layers of the bladder wall, which mimics bladder tumors. EC may present with symptoms such as increased urination frequency, dysuria, gross/microscopic hematuria, suprapubic pain and urinary retention. Case Presentation: We present a 17-year-old male patient, who was continent night and day in his childhood, and was admitted to our clinic for complaints of hematuria and nocturnal enuresis for the past six months. His history and physical examination were unremarkable, and routine hematological and biochemical tests were normal. Cystoscopy revealed a 4 x 3 cm erythematous, polypoidal, solid lesion on the bladder dome. Histopathological examination of the lesion revealed transitional epithelium with stromaledema, where diffuse, dense infiltration of lamina propria by eosinophils and lymphocytes was also seen. According to these findings, a histopathological diagnosis of EC was made, and the patient was treated with corticosteroids, antimicrobial agents and antihistamines. His symptoms dramatically improved and nocturnal enuresis also recovered after treatment. Conclusions: Although it is a rare entity, EC should be kept in mind in the differential diagnosis of patients presenting with dysuria, hematuria and any kind of acquired voiding dysfunction, including frequency, pollakiuria and incontinence.

This study derived measures to reduce exposure doses by identifying factors which affect the external radiation dose rate of patients treated with radiopharmaceuticals for PET-CT tests. The external radiation dose rates were measured on three parts of head, thorax and abdomen at a distance of 50cm from the surface of 60 PET-CT patients. It showed there are changes in factors affecting the external radiation dose rate over time after the administration of F-18 FDG. The external radiation dose rate was lower in the patients with more water intake than those with less water intake before the injection of radiopharmaceuticals at all three points: right after the injection of radiopharmaceuticals (average 4.17 mins), after the pre-PEET-CT urination step (average 77.47 mins), and right after the PET-CT test (average 114.15 mins). The study also found there is a need to increase the amount of water intake before the injection of radiopharmaceuticals in order to maintain a low external radiation dose rate in patients. This strategy is only possible under the assumption that the quality of the video has not changed after conducting this study on the relations between the image and quality. This study also found a need to use radiopharmaceuticals with the minimum amount needed for each patient because F-FDG doses affects the external radiation dose rate at the point right after the injection of radiopharmaceuticals. Urination frequency was the most significant factor to affect the external radiation dose rates at the point right after the PET-CT test and the point after the pre-PET-CT urination step. There is a need to realize the strategy to increase the urination frequency of patients to maintain the external radiation dose rate low (average 77.47 mins) before and after the injection of radiopharmaceuticals. In addition, at this point, there is a need to take advantage of personal strategies because the external radiation dose rate is lower if the fasting time is shorter, the contrast medium is used, and the amount of water intake is increased after the administration of radiopharmaceuticals. Finally this study found the need to be able to generalize these findings through an in-depth research on the factors affecting the external radiation dose rate, which includes radiopharmaceutical dose, urination frequency, the amount of water intake, fasting time and the use of contrast medium.

Background: Health issues relating to the lower urinary tract are an increasing burden on the health economy. Measurement of urination frequency/volume using diaries to evaluate symptoms and assess severity is established in the management of these health problems. In current practice, these frequency volume diaries are completed by voiding into a measuring jug and the completion of paper or digital charts. Despite being shown useful to diagnosis, this can be a cumbersome method of data collection, leading to issues with patient compliance. In this paper we describe the established benefits of providing clinicians accurate micturition data followed by an analysis of the problems with the current data collection method. Methods: We introduce our prototype electronic device and accompanying method, which is designed to improve data accuracy and patient compliance, while reducing patient training requirements and clinician workload. Results: The device hardware calibration and testing procedure is described, and two sets of initial data from assumed healthy volunteers are presented, allowing us to demonstrate the advantages of digital data in the fast calculation of diary summary statistics and their potential use to clinicians. Conclusions: We discuss the design improvements to the UScale device, collection bag, and electronic medical records integration undertaken while validating our described method.

Urine excreted in patches by grazing livestock accounts for much of the nitrogen (N) loss to the environment in grazing systems. These losses arise mainly through N leaching to ground water and gaseous losses to the atmosphere. Models of grazing systems ideally require data on urination frequency, N load in each urination event and spatial distribution patterns of urine. To date there has been a lack of suitable equipment for obtaining information on urination characteristics of grazing animals. This paper describes a urine sensor that detects and logs each urination event of female sheep and cattle. A thermistor suspended below the vulva continuously measures ambient temperature except when urine passes over it, causing the temperature to rise to near body temperature. Field validation showed 85% and 78% of sensor-detected urination events by sheep and cattle sensors, respectively, were seen by the observer. Some of the urination events identified by the sensor but not seen by the observer were confirmed by video footage. For cattle, only one observed urination event was not detected by the urine sensor, giving a 4% error rate of detection. Daily urination frequencies (ewes: 13-23eventsday^-^1; cows: 11-26eventsday^-^1) were similar to published data for these species. A custom-made GPS unit worn on the rump of the ewe and on the collar of the cow logged animal position continuously so that urine patch position could be determined. Examples of urine distribution patterns by ewes and beef cows in large, hilly paddocks clearly show campsite locations where a disproportionate number of urination events occurred. For sheep, the correlation between time spent in an area and the number of urination events in the same area was r=0.82, but this correlation was weaker for cattle (r=0.54).

The overall evidence of an association between fluid intake and bladder cancer is not entirely consistent. We examined the fluid intake-bladder cancer relationship in the Los Angeles bladder cancer case-control study. A total of 1,586 cases and their age-, sex-, and race-matched neighborhood controls were interviewed in-person from 1987 to 1999. Information on total fluid intake was derived from the consumption of specific fluids including water, coffee, tea, alcohol, milk, juice, hot chocolate and soda. Total fluid intake was not associated with bladder cancer. Daily water intake was associated with a slight decrease in bladder cancer risk, with the protection more pronounced among women (p for trend = 0.039) than among men (p for trend = 0.62). Compared to drinking

A model was developed as a tool for designing straw-bedded sow group-housing systems with low ammonia emission. Using mechanistic and empirical relationships it calculates the total ammonia emission by integrating ammonia volatilisations from all the urine pools in the house. The reference data were from a house with a floor comprising 60% straw bedding, 14% drinking area (slatted floor with pit), 3% waiting area (slatted floor with pit) and 23% alley (solid floor). Simulations were performed to elucidate the effect of the distribution of the urinations over the different surfaces, relating this to the size and distribution of the urine pools, and the area of the surfaces urinated upon. The results were compared with emission data from an entire sow house. When the default settings were a urine production of 7 l/d per sow, a urination frequency of 5 times a day per sow, and urinations distributed evenly over the four emitting surfaces the model estimated the ammonia emission from the entire house as 11.7 g/d per sow, and the relative contributions of the straw bed, the drinking area, the waiting area and the alley as, respectively, 27%, 22%, 9% and 42%. By comparison, the actual emission from the house was 8.7 g/d per sow. The 90% confidence interval was 6.5¿10.9 g/d per sow. Increasing the size of the urine pool from 0.14 m2 to 1.40 m2 in the model simulations caused ammonia emission initially to increase from 9.7 to 12.1 g/d per sow when the pool volume was 0.47 m2. If the pool was bigger, emission fell to 10.6 g/d per sow because, though the larger emitting area increases ammonia emission, the increase is outweighed by the reduction in emission caused by successive, superseding urinations on the same spot. If the entire emitting area was assumed to be straw bedding, the calculated emission from the house was 5.8 g/d per sow. Assuming slatted and concrete floors without straw bedding increased the emission to 16.5 g/d per sow. It is concluded that measures to reduce the ammonia emission from the bedded sow house should be aimed at decreasing the emission from the solid floor and/or allowing more urinations on the straw bed. The model is a useful design tool for achieving emission reduction from group-housing systems for sows with straw bedding. Its predictive power would be improved by inputting data on the actual size of the urine pool and urinating behaviour of sows.

This paper presents our initial efforts towards the development of screen printed sensors on folded paper substrates for multi-modal sensing of biopotentials, wetness, and pressure. These sensors contain three layers of sensing stripes forming a 16-pixel array where various layers are utilized for different sensing modalities. The performance of the paper-based sensors was assessed. The sensors were shown to exhibit a linear capacitive response to changes in force, as well as a decrease in impedance in the presence of wetness. We discuss the integration of these low-cost and partially disposable paper-based sensors into a wearable diaper system for Bluetooth-based wireless heart rate monitoring, respiratory rate tracking and urination frequency and amount detection.

Dehydration has been related to several health aspects, and children are especially vulnerable. Since children spend a large time at school, we aim to examine children’s hydration status at school-start and its change during the school-day by objective measures. To identify subpopulations at risk, determinants of hydration were tested. In 371 Belgian 7–13-year-old children, hydration was measured by (1) urinary osmolality at school-start and by a pooled school-day sample; (2) body water% by impedance; (3) parental reported beverage consumption; (4) urination frequency. Linear regression analyses were used to test putative predictors of hydration status: age, sex, parental education, region (Dutch-speaking versus French-speaking part of Belgium), diet quality and adiposity. A mean osmolality of 888 mosmol/kg was found in the school-start sample and 767 mosmol/kg in the school-day sample. This resulted in, respectively, 76 and 54 % of the children being dehydrated (>800 mosmol/kg). In 45 % of the children, the hydration level decreased over the school-day. Also the body water% as derived from bio-impedance (57 % ±4), the reported average daily beverage intake (911 ml) and the lower urination frequency during weekdays versus weekend days confirmed the low hydration status in our school population. Boys, Walloon children and those with higher adiposity were at increased risk of low hydration level. Diet quality was not the predictor of hydration status. Hydration status at school appeared problematic in this population. This emphasizes the need for more resources and attention by school management and governmental organizations. Herein, especially Walloon schools and boys should be reached.

Summary Introduction A bladder diary (BD) is a simple and non-invasive method of evaluating people with lower urinary tract symptoms (LUTS). Recently, the ICCS recommended a 48-h daytime frequency and volume chart (which does not need to be recorded on 2 consecutive days) to evaluate lower urinary tract (LUT) dysfunction. However, some studies on adults have demonstrated that a minimum of 3 days is required. It is believed that, to date, there are no studies in the literature that compare a 2-day BD with a 3-day BD. The advantages of a BD over a shorter period of time are the simplicity and possible better parent compliance. Objective The aim of this study was to evaluate if a 2-day BD is statistically and clinically comparable to a 3-day BD. Study design A voiding diary was filled in over a 3-day period for 92 children (ages ranged from to 3–16 years, mean 7.9 ± 3.07) attending the present institution. By using the voiding diary, the following parameters were calculated: urination frequency, maximum and average volumes of urine (MVV and AVV) and fluid intake. The diary considered the 2 days as the first and second days of the 3-day diary. Results Out of the 92 children, eight (8.7%) did not properly complete the diary. The sample predominantly comprised females (n = 55, 59.8%). No differences were seen between 2-day and 3-day bladder diaries regarding fluid intake, maximum and average voided volume. The sensitivity, specificity, positive and negative predictive values of the 2-day bladder diary for detecting frequency were 83.4%, 91.7%, 80% and 93.2%, and for low bladder capacity they were 97.2%, 90.9%, 99% and 88%, respectively ( Table ). Discussion In a 2006 document, the ICCS recommended that a bladder diary be kept for 3 days, but in new documentation (2014) there is a reference stating that 2 days are enough. Bladder capacity is an important parameter in evaluating LUTS. Using a 2-day BD, the data showed that only a small percentage of reduced bladder capacity diagnosis would be lost. Conclusion When using the 2-day diary, a 16% false negative rate for frequency should be expected. A 2-day bladder diary is sufficient to evaluate bladder capacity and fluid intake. Table . Comparison of 2-day and 3-day voiding diaries for the number of voids and low bladder capacity. 2-day voiding diary 3-day voiding diary Higher number of voids (≥8 voids/day) Low bladder capacity ( Yes No Total Yes No Total Yes 20 (83.4%) 5 (8.3%) 25 70 (97.2%) 1 (9.1%) 71 No 4 (16.6%) 55 (91.7%) 59 2 (2.8%) 10 (90.9%) 12 Total 24 60 84 72 11 83 *Sample of 92 children. Missing value for number of voids, eight (8.7%); for bladder capacity, nine (9.7%).

Urination frequency and cystic pressure resistance have been used as end-points to assess x-ray-induced changes of bladder function. Whole or half bladders of adult male rabbits were irradiated, caudally or cranially. The absorbed dose was 33 Gy, 36 Gy or 39 Gy, given in 5 daily fractions. Animals which received a whole bladder dose of 39 Gy or 36 Gy showed increased urination frequency and enhanced bladder pressure resistance during the whole follow-up time of 100 weeks, compared with the sham-irradiated controls. At half bladder irradiation, only the highest doses (39 Gy to the cranial part of the bladder and 39 Gy or 36 Gy to the caudal part) gave rise to a slight increase in frequency at about 20 weeks after exposure.

— The influence of type of photosensitizer, drug and light dose, and time interval between photosensitizer and illumination on the extent of photodynamic therapy (PDT)-induced bladder damage and recovery was investigated using a mouse model. The three photosensitizers studied were Photofrin, meso-tetrahydroxyphenylchlorin (m-THPC) and bacteriochlorin a (BCA). Functional bladder damage was quantitatively assessed from increases in urination frequency index (FI) at 1-35 weeks after illumination and histological damage was qualitatively assessed at 1 day, 1, 2 and 12 weeks. Photofrin-mediated PDT caused an acute increase in FI at 1 week, with recovery within 2-8 weeks after light doses of 2.7-8.2 J/cm2. After higher light doses there was only partial recovery. Previous results indicated that the acute response and rate of recovery was the same whether Photofrin was given at 1 day or up to 7 days before illumination. The m-THPC-mediated PDT at drug doses of 0.3 mg/kg also resulted in a marked acute response with good recovery, even after 10.8 J/cm2. Lower drug doses in combination with 5.4 J/cm2 did not result in acute or late damage. There was no significant difference in acute response when m-THPC was given 1, 3 or 7 days before illumination, although recovery was faster for the longer illumination intervals (3 or 7 days). Illumination at 1 h after 20 mg/kg BCA induced an acute response within 2 days after illumination, with recovery within 4-8 weeks. Lower drug doses did not result in damage. The most prominent histological changes during the acute period with all three photosensitizers were submucosal edema and vessel dilation, with epithelial denudation (depending on drug/light dose). We conclude that BCA and m-THPC are both potent new photosensitizers. They can induce a moderate to severe acute bladder response with complete healing over a period of a few weeks. The photosensitizer m-THPC is very effective with low doses of photosensitizer and light, whereas relatively high doses of BCA and light are required to obtain equivalent functional bladder damage in our mouse model.

Functional and histological damage after intravesical administration of mitomycin C or doxorubicin were studied in mouse bladders. Dosing schedules were based on those commonly used in the clinic, and bladder function was assessed from changes in urination frequency. Repeated weekly instillations of 1 mg./ml. mitomycin C induced a transient three-fold increase in Frequency Index (FI) with recovery to control levels within 3 weeks. Weekly instillations of 6 mg./ml. doxorubicin also resulted in a three-fold increase in FI, but lower doses produced only minimal changes. There was, again, full recovery within 3 weeks. Our experiments indicate that repeated intravesical instillations of mitomycin C or doxorubicin are well tolerated, with rapid recovery from functional damage within a few weeks of cessation of therapy. There was significantly less damage after repeated instillations of clinically relevant doses of doxorubicin than mitomycin C.

Functional damage in the mouse bladder was measured sequentially from 1 to 53 weeks after irradiation with a range of X ray doses (10 to 30 Gy). Damage was assessed from the independent assays of urination frequency and cystometric measurement of bladder volume at a constant intravesical pressure. There was an early, transient wave of damage from 1 to 3 weeks after bladder irradiation. During this period the urination frequency was increased to greater than or equal to 2 times control levels in 20 to 70% of the mice (depending on dose) after 15 to 30 Gy. Bladder volume was reduced to less than or equal to 50% of control values in 20 to 40% of the mice after doses of 20 to 30 Gy. This early damage usually lasted for less than 1 week and occurred at times ranging from 5 to 21 days, independent of dose. There was no significant correlation between response as measured by the two assays on an individual animal basis during the early period. The incidence of reduced bladder volume, measured cystometrically in anesthetized mice, tended to be less than the incidence of increased urination frequency, measured in non-anesthetized animals. Late bladder damage developed from 16 to 40 weeks after doses of greater than or equal to 20 Gy, and the time of onset was inversely related to dose. Less than 20% of mice treated with 10 to 15 Gy developed late bladder damage as assessed by increased urination frequency or reduced bladder volume. Late bladder damage was irreversible and there was a good correlation between response of individual animals as measured by the two assays. We conclude that changes in both urination frequency and bladder volume can be used as quantitative measures of early and late functional damage after bladder irradiation. The early, transient damage was not associated with changes in the urothelium or muscle layers of the bladder, whereas the late, persistent damage was accompanied by epithelial denudation and focal hyperplasia, with fibrosis and ulceration after higher doses.

Mouse bladders were irradiated with 1,2,4 or 8 fractions of electrons or neutrons. Urination frequency was scored from 9 to 14 months after irradiation and this was used as a measure of the extent of bladder damage. The RBE for neutrons relative to 1.8 MeV electrons increased from 3.2 for large single doses to 5.4 for 8 fractions. Repair of sublethal injury after electron irradiation was considerable, with 63-72% of each fractionated dose repaired. Repair after neutron irradiation was less, with only 35-43% of each fractionated dose recovered. Linear-quadratic analysis of all the fractionated bladder data yielded an alpha/beta ratio for electrons of 6-7 Gy and, surprisingly, the alpha/beta ratio for neutrons was only slightly higher at about 8 Gy.

Excessive frequency of urination (preceded by an excessive urge to urinate) in a male student was treated by requiring him to refrain from urinating for progressively longer periods of time during a 12-hr period each day (Fixed Period) while allowing him to urinate freely during the remaining 12 hr (Free Period). Over a 31-week treatment period, urination frequency declined to within normal limits during both Fixed and Free Periods and normal urination frequency was maintained during a 1-year follow-up period.

The capacity for repair of sublethal damage during fractionated irradiation of the mouse bladder has been measured. Graded doses of electrons were given as 1, 2 or 5 equal daily fractions. Two functional end points were used to assess bladder damage: a) increased urination frequency and b) decreased bladder capacity. Repair of sublethal injury within 24 hours was found to be similar using both assays for bladder damage and was greater than the repair observed in mouse skin for a given dose per fraction. The possibility of a slower repair process occurring in bladder was investigated by giving two fractions in increasing overall times (from 24 hours to one month). No increased repair was observed with the longer time intervals; hence there was no evidence for slow repair in the bladder.

The urinary flow, measured as changes in medium conductivity, was investigated during the moult cycle of Crangon vulgaris living in 10%0 at 20.5 °C. The urination frequency in an intermoult animal was once per 50-55 minutes, while the frequency in the early postmoultincreased to once per 15-20 minutes. A continous recording of the urination frequency during the moult showed a decrease in late pre moult from the intermoult values to once per 60-80 minutes. Together with a fall in urine production this indicates that part of the increase in water content prior to ecdysis is caused by decreasing diuresis. The urine production in the intermoult was found to be around 20 μl · g-1 · h-1. After the moult the production increased to 50-60 μl · g-1 · h-1. The changes in diuresis are interpreted as changes in water fluxes due to, among other factors, changes in surface permeability.

Summary The response of the mouse bladder to cyclophosphamide (Cy) and radiation, used alone or in combination, has been assessed in order to investigate whether epithelial denudation is the primary step in the sequence of events leading to bladder dysfunction, as expressed by increased urination frequency. The response to the two agents when used singly is consistent with the epithelium being the target tissue. However, early Cy denudation of the epithelium accompanied by rapid epthelial turnover, does not influence the time of onset of radiation dose-related bladder damage. Thus it appears that denudation of the bladder epithelium is not necessarily the immediate precursor of radiation injury.

The response of mouse bladders to multifraction irradiation was assessed from increases in urination frequency or the reduction in bladder capacity after irradiation. A range of electron doses were given as 1, 2, 5, 10 or 20 equal fractions in overall treatment times of 1-2 weeks. Dose-related increases in urination frequency were measured from 10 to 14 months after irradiation and a dose-related reduction in bladder capacity (at inflation pressures of 20 mm Hg) was apparent at the time of sacrifice. The extent of repair of sublethal and potentially lethal damage was estimated from a comparison of the isoeffective doses in fractionated regimes and single dose treatments. After small doses per fraction (2.5-6 Gy), the extent of repair in bladder was very similar to that in mouse skin. After larger doses per fraction (greater than 8 Gy) slightly more repair was seen in bladder than skin. Linear-quadratic analysis of the data suggests quite a high value for the ratio alpha/beta, in the region of 5 to 10 Gy. This is higher than the alpha/beta ratios which have been reported for most other slowly dividing normal tissues.

The response of the mouse bladder to single doses of cyclophosphamide (CY), X-rays, or their combination was assessed from the development of functional damage (haematuria and increased frequency of urination). For the combined treatments, a single dose of CY (100 mg · kg −1 ) was given immediately before or at intervals of up to 9 months before irradiation, or at one week to 9 months after irradiation. Damage after X-rays alone was expressed late, with no functional changes earlier than 5 months. CY alone, by contrast caused a marked increase in urination frequency and haematuria within one week. There was subsequently partial recovery although some residual damage persisted for at least one year. CY given before or after X-rays caused an early, X-ray dose-related expression of damage. These results suggest that the drug precipitated some of the latent radiation injury. There was also a second wave of damage after the combined treatments and the response at 9–12 months was always more severe than after X-rays alone. This increased late damage could be explained in terms of additive drug and radiation toxicities. Since drug given up to 9 months before or after irradiation caused more severe bladder damage than X-rays alone, CY should be avoided in clinical situations where the bladder has been irradiated.

Ultraviolet light has been used to examine urine marks deposited by adult male house mice on filter paper on the floors of their cages during overnight tests. Both the urination frequency and the pattern in which urine was deposited on the filter paper depended upon social rank. Dominant males vigorously marked their entire cage floor, whereas subordinate males typically voided urine in only two to four pools in the corners of their cages.

The radiation response of the mouse urinary bladder was assessed by measuring the urination frequency after localized irradiation with 1.8-MeV electrons. The onset of radiation-induced incontinence is late, no changes were observed before 5 months after doses of up to 40 Gy (4000 rad). Beyond this time good dose--response curves were obtained above a threshold dose of 15 Gy. The time of onset of radiation damage was earlier after higher doses, but in all cases the maximum damage was observed by 12 months. There was some recovery of bladder function, especially in the lower dose groups, by 16 months. The increased frequency at 5 to 12 months was associated with epithelial denudation and a loss of the specialized polyploid surface cells. Fibrosis of the deeper layers was not apparent until after 12 months. The increased urination frequency responses are correlated with the delayed compensatory proliferation of the epithelium and with the resistance of the bladder to inflation under applied pressure, which also gave a dose-response relationship at 18 months.