Renal and cardiovascular effects of caffeine:a dose-response study

The effects of increasing oral doses of caffeine (45, 90, 180 and 360 mg) on effective renal plasma flow (ERPF), plasma renin activity (PRA), serum electrolytes, plasma noradrenaline, blood pressure and heart rate were studied in eight healthy male volunteers. Urine volume was increased by 360 mg of caffeine only. At caffeine doses greater than 90 mg urinary sodium excretion was significantly increased. There were no changes in ERPF. Serum potassium was significantly reduced by 360 mg of caffeine. Caffeine increased systolic pressure in a dose related manner. Diastolic pressure was also increased, but not in relation to dose. A 360 mg dose of caffeine produced a late increase in heart rate. These changes were not associated with any alterations in PRA or in plasma noradrenaline.

The impact of a rice based diet on urinary arsenic

Rice is elevated in arsenic (As) compared to other staple grains. The Bangladeshi community living in the United Kingdom (UK) has a ca. 30-fold higher consumption of rice than white Caucasians. In order to assess the impact of this difference in rice consumption, urinary arsenicals of 49 volunteers in the UK (Bangladeshi n = 37; white Caucasians n = 12) were monitored along with dietary habits. Total urinary arsenic (As(t)) and speciation analysis for dimethylarsinic acid (DMA), monomethylarsonic acid (MA) and inorganic arsenic (iAs) was conducted. Although no significant difference was found for As(t) (median: Bangladeshis 28.4 µg L(-1)) and white Caucasians (20.6 µg L(-1)), the sum of medians of DMA, MA and iAs for the Bangladeshi group was found to be over 3-fold higher (17.9 µg L(-1)) than for the Caucasians (3.50 µg L(-1)). Urinary DMA was significantly higher (p <0.001) in the UK Bangladeshis (median: 16.9 µg DMA L(-1)) than in the white Caucasians (3.16 µg DMA L(-1)) as well as iAs (p <0.001) with a median of 0.630 µg iAs L(-1) for Bangladeshi and 0.250 µg iAs L(-1) for Caucasians. Cationic compounds were significantly lower in the Bangladeshis (2.93 µg L(-1)) than in Caucasians (14.9 µg L(-1)). The higher DMA and iAs levels in the Bangladeshis are mainly the result of higher rice consumption: arsenic is speciated in rice as both iAs and DMA, and iAs can be metabolized, through MA, to DMA by humans. This study shows that a higher dietary intake of DMA alters the DMA/MA ratio in urine. Consequently, DMA/MA ratio as an indication of methylation capacity in populations consuming large quantities of rice should be applied with caution since variation in the quantity and type of rice eaten may alter this ratio.

Altered porphyrin excretion and histopathology of greylag geese (Anser anser) exposed to soil contaminated with lead and arsenic in the Guadalquivir Marshes, southwestern Spain

Greylag geese (Anser anser) in the Guadalquivir Marshes (southwestern Spain) can be exposed to sources of inorganic pollution such as heavy metals and arsenic from mining activities or Pb shot used for hunting. We have sampled 270 fecal excreta in different areas of the marshes in 2001 to 2002 to evaluate the exposure to Pb, Zn, Cu, Mn, and As and to determine its relationship with soil ingestion and with the excretion of porphyrins and biliverdin as biomarkers. These effects and the histopathology of liver, kidney, and pancreas were also studied in 50 geese shot in 2002 to 2004. None of the geese had ingested Pb shot in the gizzard. This contrasts with earlier samplings before the ban of Pb shot for waterfowl hunting in 2001 and the removal of Pb shot in points of the Doñana National Park (Spain) in 1999 to 2000. The highest exposure through direct soil ingestion to Pb and other studied elements was observed in samples from Entremuros, the area of the Doñana Natural Park affected by the Aznalcóllar mine spill in 1998. Birds from Entremuros also more frequently showed mononuclear infiltrates in liver and kidney than birds from the unaffected areas, although other more specific lesions of Pb or Zn poisoning were not observed. The excretion of coproporphyrins, especially of the isomer I, was positively related to the fecal As concentration, and the ratio of coproporphyrin III/I was positively related to fecal Pb concentration. Biliary protoporphyrin IX concentration was also slightly related to hepatic Pb concentration. This study reflects biological effects on terrestrial animals by the mining pollution in Doñana that can be monitored with the simple noninvasive sampling of feces.

Association between tortilla consumption and human urinary fumonisin B1 levels in a Mexican population

Fumonisins are mycotoxins produced by Fusarium spp. and commonly contaminate maize and maize products worldwide. Fumonisins are rodent carcinogens and have been associated with human esophageal cancer. However, the lack of a valid exposure biomarker has hindered both the assessment of human exposure and the evaluation of disease risk. A sensitive liquid chromatography-mass spectrometry method to measure urinary fumonisin B1 (FB1) following extraction on Oasis MAX cartridges was established and applied to urine samples from women in a cohort recruited in Morelos County, Mexico. Urinary FB1 was compared with dietary information on tortilla consumption. FB1 recovery in spiked samples averaged 94% as judged by deuterium-labeled FB1 internal standard. Urinary FB1 was determined in 75 samples from women selected based on low, medium, or high consumption of maize-based tortillas. The geometric mean (95% confidence interval) of urinary FB1 was 35.0 (18.8-65.2), 63.1 (36.8-108.2), and 147.4 (87.6-248.0) pg/mL and the frequency of samples above the detection limit (set at 20 pg FB1/mL urine) was 45%, 80%, and 96% for the low, medium, and high groups, respectively. Women with high intake had a 3-fold higher average FB1 levels compared with the "low intake" group (F = 7.3; P = 0.0015). Urinary FB1 was correlated with maize intake (P-trend = 0.001); the correlation remained significant after adjusting for age, education, and place of residence. This study suggests that measurement of urinary FB1 is sufficiently sensitive for fumonisin exposure assessment in human populations and could be a valuable tool in investigating the associated health effects of exposure.

Effect of a multifaceted intervention on number of antimicrobial prescriptions for suspected urinary tract infections in residents of nursing homes:Cluster randomised controlled trial

Objective: To assess whether a multifaceted intervention can reduce the number of prescriptions for antimicrobials for suspected urinary tract infections in residents of nursing homes. Design: Cluster randomised controlled trial. Setting: 24 nursing homes in Ontario, Canada, and Idaho, United States. Participants: 12 nursing homes allocated to a multifaceted intervention and 12 allocated to usual care. Outcomes were measured in 4217 residents. Interventions: Diagnostic and treatment algorithm for urinary tract infections implemented at the nursing home level using a multifaceted approach-small group interactive sessions for nurses, videotapes, written material, outreach visits, and one on one interviews with physicians. Main outcome measures: Number of antimicrobials prescribed for suspected urinary tract infections, total use of antimicrobials, admissions to hospital, and deaths. Results: Fewer courses of antimicrobials for suspected urinary tract infections per 1000 resident days were prescribed in the intervention nursing homes than in the usual care homes (1.17 v 1.59 courses; weighted mean difference -0.49, 95% confidence intervals -0.93 to -0.06). Antimicrobials for suspected urinary tract infection represented 28.4% of all courses of drugs prescribed in the intervention nursing homes compared with 38.6% prescribed in the usual care homes (weighted mean difference -9.6%, -16.9% to -2.4%). The difference in total antimicrobial use per 1000 resident days between intervention and usual care groups was not significantly different (3.52 v 3.93; weighed mean difference -0.37, -1.17 to 0.44). No significant difference was found in admissions to hospital or mortality between the study arms. Conclusion: A multifaceted intervention using algorithms can reduce the number of antimicrobial prescriptions for suspected urinary tract infections in residents of nursing homes.

Evidence-Based Clinical Pathways To Manage Urinary Tract Infections in Long-Term Care Facilities:A Qualitative Case Study Describing Administrator and Nursing Staff Views

Objectives: This article examines the views of nursing staff and administrators in long-term care facilities (LTCFs) regarding a clinical pathway for managing urinary tract infections (UTIs) in LTCF residents. Design: A qualitative (case study) design was used. Setting: Data were collected from 8 LTCFs in southern Ontario and 2 in Iowa enrolled in a larger randomized controlled trial of clinical pathway for managing UTIs in LTCF residents, conducted between September 2001 and March 2003. The clinical pathway, designed to more effectively identify, diagnose, and treat UTIs, and reduce inappropriate antibiotics use for asymptomatic UTIs, introduced 2 decision tools to determine when to order a urine culture and initiate antibiotic treatment for suspected UTIs. Participants: We conducted 19 individual interviews with administrators and 10 focus groups with 52 nurses. Findings: Nurses generally thought that the pathways were well developed and easy to use, and administrators believed they were an important educational resource. Barriers to their use varied by group-initial lack of buy-in from nurses (medical directors), additional work (directors of nursing), and the need to change the protocol to exclude certain residents based on prior health conditions and/or pressure from physicians or families (nurses). Conclusions: Both administrators and staff, once familiar with a new clinical protocol to improve UTI management in LTCFs, generally supported its use. © 2007 American Medical Directors Association.

Combination of CFD and DOE to analyze and improve the mass flow rate in urinary catheters

The urinary catheter is a thin plastic tube that has been designed to empty the bladder artificially, effortlessly, and with minimum discomfort. The current CH14 male catheter design was examined with a view to optimizing the mass flow rate. The literature imposed constraints to the analysis of the urinary catheter to ensure that a compromise between optimal flow, patient comfort, and everyday practicality from manufacture to use was achieved in the new design. As a result a total of six design characteristics were examined. The input variables in question were the length and width of eyelets 1 and 2 (four variables), the distance between the eyelets, and the angle of rotation between the eyelets. Due to the high number of possible input combinations a structured approach to the analysis of data was necessary. A combination of computational fluid dynamics (CFD) and design of experiments (DOE) has been used to evaluate the "optimal configuration." The use of CFD couple with DOE is a novel concept, which harnesses the computational power of CFD in the most efficient manner for prediction of the mass flow rate in the catheter. Copyright © 2009 by ASME.

Deoxynivalenol exposure assessment in young children in Tanzania

Scope: This study assessed deoxynivalenol (DON) exposure in children from three geographic locations within Tanzania, over three time points in 1 year, using a urinary biomarker of exposure.

Methods and results: A total of 166 children aged 6-14 months were studied at a maize harvest and followed up twice at 6-month intervals. On two consecutive days, morning urine was collected from each child and urinary DON was measured using an LC-MS method, with and without beta-glucuronidase hydrolysis in order to assess free DON (fDON) and glucuronide DON. Overall, urinary DON increased significantly along with the three visits (geometric mean 1.1, 2.3, and 5.7 ng/mL, at visits 1, 2, and 3, respectively, p <0.01). fDON was 22% of urinary total DON. Urinary DON excretion rate was 74% in village Kikelelwa based on food DON level and food consumption. Assuming 360 mL of urine excreted per day, 10, 19, and 29% of children at visits 1, 2, and 3, respectively, exceeded the provisional maximum tolerable daily intake of 1000 ng/kg b.w./day.

Conclusion: Young children in Tanzania are chronically exposed to DON due to eating contaminated maize, although exposure levels varied markedly by region and season.

Multiple mycotoxin exposure determined by urinary biomarkers in rural subsistence farmers in the former Transkei, South Africa

Subsistence farmers are exposed to a range of mycotoxins. This study applied novel urinary multi-mycotoxin LC-MS/MS methods to determine multiple exposure biomarkers in the high oesophageal cancer region, Transkei, South Africa. Fifty-three female participants donated part of their maize-based evening meal and first void morning urine, which was analysed both with sample clean-up (single and multi-biomarker) and by a 'dilute-and-shoot' multi-biomarker method. Results were corrected for recovery with LOD for not detected. A single biomarker method detected fumonisin B1 (FB1) (87% incidence; mean±standard deviation 0.342±0.466 ng/mg creatinine) and deoxynivalenol (100%; mean 20.4±49.4 ng/mg creatinine) after hydrolysis with β-glucuronidase. The multi-biomarker 'dilute-and-shoot' method indicated deoxynivalenol-15-glucuronide was predominantly present. A multi-biomarker method with β-glucuronidase and immunoaffinity clean-up determined zearalenone (100%; 0.529±1.60 ng/mg creatinine), FB1 (96%; 1.52±2.17 ng/mg creatinine), α-zearalenol (92%; 0.614±1.91 ng/mg creatinine), deoxynivalenol (87%; 11.3±27.1 ng/mg creatinine), β-zearalenol (75%; 0.702±2.95 ng/mg creatinine) and ochratoxin A (98%; 0.041±0.086 ng/mg creatinine). These demonstrate the value of multi-biomarker methods in measuring exposures in populations exposed to multiple mycotoxins. This is the first finding of urinary deoxynivalenol, zearalenone, their conjugates, ochratoxin A and zearalenols in Transkei.

Synthesis and release kinetics of polymerisable ester drug conjugates towards pH-responsive infection-resistant urinary biomaterials

Herein we report the synthesis, characterisation and hydrolytic release kinetics of a suite of novel, polymerisable ester quinolone conjugates with varying alkenyl chain lengths. Hydrolysis was shown to proceed up to 17-fold faster upon elevation of pH from neutral to pH 9.29, making these conjugates attractive for the development of 'designer' infection-resistant urinary biomaterials exploiting the increase in urine pH reported at the onset of catheter-associated infection to trigger drug release. (C) 2013 Elsevier Ltd. All rights reserved.

Urethral atrophy after artificial urinary sphincter placement:Is cuff downsizing effective?

Purpose: We reviewed the outcome of cuff downsizing with an artificial urinary sphincter for treating recurrent incontinence due to urethral atrophy.

Materials and Methods: We analyzed the records of 17 patients in a 7-year period in whom clinical, radiological and urodynamic evidence of urethral atrophy was treated with cuff downsizing. Cuff downsizing was accomplished by removing the existing cuff and replacing it with a 4 cm. cuff within the established false capsule. Incontinence and satisfaction parameters before and after the procedure were assessed by a validated questionnaire.

Results: Mean patient age was 70 years (range 62 to 79). Average time to urethral atrophy was 31 months (range 5 to 96) after primary sphincter implantation. Mean followup after downsizing was 22 months (range 1 to 64). Cuff downsizing caused a mean decrease of 3.9 to 0.5 pads daily. The number of severe leakage episodes decreased from a mean of 5.4 to 2.1 The mean SEAPI (stress leakage, emptying, anatomy, protection, inhibition) score decreased from 8.2 to 2.4. Patient satisfaction increased from 15% to 80% after cuff downsizing. In 1 patient an infected cuff required complete removal of the device.

Conclusions: Patient satisfaction and continence parameters improved after cuff downsizing. We believe that this technique is a simple and effective method of restoring continence after urethral atrophy.

Artificial urinary sphincter implantation in the irradiated patient:safety, efficacy and satisfaction

Objective To compare the long-term outcome of artificial urinary sphincter (AUS) implantation in patients after prostatectomy, with and with no history of previous irradiation.

Patients and methods The study included 98 men (mean age 68 years) with urinary incontinence after prostatectomy for prostate cancer (85 radical, 13 transurethral resection) who had an AUS implanted. Twenty-two of the patients had received adjuvant external beam irradiation before AUS implantation. Over a mean (range) follow-up of 46 (5-118) months, the complication and surgical revision rates were recorded and compared between irradiated and unirradiated patients. The two groups were also compared for the resolution of incontinence and satisfaction, assessed using a questionnaire.

Results Overall, surgical revision was equally common in irradiated (36%) and unirradiated (24%) patients. After activating the AUS, urethral atrophy, infection and erosion requiring surgical revision were more common in irradiated patients (41% vs 11%; P <0.05); 70% of patients reported a significant improvement in continence, regardless of previous irradiation. Patient satisfaction remained high, with >80% of patients stating that they would undergo surgery again and/or recommend it to others, despite previous Irradiation and/or the need for surgical revision.

Conclusions Despite higher complication and surgical revision rates in patients who have an AUS implanted and have a history of previous Irradiation, the long-term continence and patient satisfaction appear not to be adversely affected.