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PubMed1999

Urinary trypsin inhibitor down-regulates hyaluronic acid fragment-induced prostanoid release in cultured human amnion cells by inhibiting cyclo-oxygenase-2 expression.

We postulated that urinary trypsin inhibitor (UTI), a Kunitz-type protease inhibitor, may inhibit low molecular weight hyaluronic acid (HA) fragment-induced prostanoid release and de-novo expression of the inducible cyclo-oxygenase-2 (COX-2) isoform in human term amnion cells. Purified amnion cultures were obtained from human fetal membranes and were exposed to a HA fragment (molecular weight 35 kDa) in the presence or absence of UTI (0-5.0 micromol/l). Amnion cells treated with the HA fragment (100 nmol/l) released significantly more prostanoids (PGE2 and PGF2alpha) than controls (PGE2: 2.1 +/- 0.13 pg/10(6) cells/24 h compared with 0.42 +/- 0.01, P < 0.05; PGF2alpha: 1.0 +/- 0.17 pg/10(6) cells/24 h compared with 0.13 +/- 0.01, P < 0.05). UTI inhibited HA fragment-induced prostanoid release in a dose-dependent manner, with 50% inhibitory concentration values of 0.8 micromol/l for PGE2 and 1.9 micromol/l for PGF2alpha. Western blot analyses demonstrated that protein levels of COX-2 were substantially increased in amnion cells treated with HA fragment. HA fragment-mediated COX-2 production was markedly diminished by pretreatment with UTI (1.0 micromol/l). These results are the first to demonstrate that UTI is a potent inhibitor of HA fragment-induced arachidonic acid metabolism.

Amnion↗
PubMed1989

Gallium-67 scintigraphy in the detection of infected polycystic kidneys in renal transplant recipients.

Renal transplant recipients with underlying polycystic kidney disease (PKD) may present with recurrent urinary tract infection (UTI). This is often due to persistent infection in one or both of the native polycystic kidneys. It may be necessary to remove the infected kidney in order to remove the source of persistent infection. Gallium-67 scintigraphy was performed in 11 renal transplant recipients with underlying PKD. Positive studies were obtained in four recipients who had recurrent UTI. The scan also localized which of the kidneys (native or transplant) was the site of persistent infection. These four recipients subsequently had nephrectomy of the infected polycystic kidneys as suggested by the scan. Negative scans were obtained in seven recipients who did not have recurrent UTI. Gallium scintigraphy is a useful test for detecting and localizing the site of persistent UTI in renal transplant recipients with underlying PKD who present with recurrent UTI.

False Negative Reactions↗
PubMed1980

Urinary tract infections in the female.

Special problems peculiar to urinary tract infections (UTIs) in the female include higher frequency than in males, recurrent infections, restrictions on antibiotic use during pregnancy, and the "urethral syndrome." Current concepts in the management of UTI include recognition of significant infection with total count of less than 100,000 organisms per milliliter; awareness that untreated UTI usually does not lead to progressive renal failure; importance of differentiating between upper and lower UTI; use of antibody coating of bacterial for distinguishing upper from lower UTI; evidence that 1-day (or single-dose) therapy may be adequate for cystitis, whereas pyelonephritis usually requires treatment beyond 2 weeks; evidence of effective prophylaxis; and indications that Chlamydia may be responsible for some cases of urethral syndrome.

Adolescent↗
PubMed1994

Interleukin 6 response to urinary tract infection in childhood.

This study analyzed the interleukin 6 (IL-6) response in 114 children with suspected urinary tract infection (UTI). Urine and serum samples were obtained at the time of enrollment. There were 90 children with UTI, 41 with and 49 without a temperature > or = 38.5 degrees C. The remaining 24 children did not have bacteriuria; 11 were febrile and 13 were not. The urinary IL-6 concentrations were higher in the children with UTI (mean, 129 units/ml) than in the children without bacteriuria (mean, 7 units/ml, P < 0.01). In contrast the serum IL-6 did not differ between children with or without UTI or between children with or without a temperature > or = 38.5 degrees C. The urinary IL-6 response was higher in children who were infected with P fimbriated Escherichia coli than in other children with UTI (P < 0.05). There was a correlation of urinary IL-6 with the degree of proteinuria, hematuria and urinary leukocyte counts (P < 0.001, P < 0.05, P < 0.05, respectively) but not with serum IL-6, CRP or temperature, and of serum IL-6 to C-reactive protein (P = 0.053) and renal concentrating capacity (P < 0.05). The results demonstrate that infections of the urinary tract activate an IL-6 response in children and that the magnitude of the IL-6 response is influenced by the properties of the infecting strain.

Adolescent↗
PubMed1996

Urinary tract infection in nephrotic syndrome.

BACKGROUND: The aim was to study the frequency, etiology and predisposing factors of urinary tract infection (UTI) in children with nephrotic syndrome. METHODS: A retrospective analysis of all children with nephrotic syndrome was made to determine the occurrence of infectious complications. RESULTS: UTI was found to be the most common infection (40.26%); 49 episodes of culture-positive UTI were observed in 37 children. All 49 episodes occurred in patients who were initially considered to be steroid nonresponders or in relapse. Fourteen of the 49 episodes (28.6%) were asymptomatic. One child had Grade IV reflux and another had a ureteric calculus. The majority of the children had no underlying urinary tract malformations. The children with UTI had significantly lower serum albumin (P < 0.05) and higher serum cholesterol (P < 0.001) concentrations than the group of 206 children without infections. Non-Escherichia coli organisms accounted for 39% of the culture isolates. CONCLUSIONS: We believe that UTI is an important but often underdiagnosed infection in children with nephrotic syndrome.

Adolescent↗
PubMed1998

Utility of dipstick urinalysis as a guide to management of adults with suspected infection or hematuria.

BACKGROUND: This study was done to determine whether emergency department (ED) patient management decisions made on the basis of dipstick urinalysis are altered when results of urine microscopy become available. METHODS: The study population was a prospective random sample of adult ED patients who had urinalysis ordered for detection of possible urinary tract infection (UTI) or hematuria. Clinicians were given the result of the dipstick urinalysis and were asked to formulate a management plan. Urine microscopy of the same specimen was obtained later, and the clinicians were asked if management was changed after results were known. RESULTS: Of 166 urinalyses, 118 (71%) were ordered for suspected UTI, 32 (19%) for suspected hematuria, and 16 (10%) for both. Of 134 urinalyses, 58 (43%) were positive for leukocyte esterase or nitrites, and 15 of 48 (31%) were positive for blood. Microscopy prompted a management change in only 9 of 166 patients. Six changes resulted in therapy for UTI, one resulted in withholding of therapy for UTI, and two resulted in cancellation of plans for diagnostic imaging. When urinalysis was done only to detect hematuria, none of the 32 patients had a management change after microscopy. CONCLUSION: Dipstick urinalysis for blood or UTI is a reliable diagnostic test in ED patients. In 94% of patients, subsequent findings on urine microscopy did not prompt a change in management. Microscopy added nothing to dipstick results when clinicians suspected conditions causing hematuria alone. Primary use of dipstick urinalysis, with microscopy in selected cases, would likely result in considerable cost and time saving without compromising patient care.

Adolescent↗
PubMed1993

Effect of protease inhibitor on ischemia/reperfusion injury of the rat liver.

The purposes of this study were to clarify the role of neutrophilic proteases in the pathogenesis of hepatic ischemia/reperfusion injury and to determine whether urinary trypsin inhibitor (UTI) pretreatment attenuated liver ischemia/reperfusion injury in rats. Livers from male Sprague-Dawley rats were subjected to 90 min of no-flow warm ischemia followed by 120 min of reperfusion. Rats were divided into a UTI group and a control group. In the control group, 120-min reperfusion of the liver produced a significant increase in myeloperoxidase activity, a significant decrease in ATP and energy charge, and a marked increase in the serum aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase levels. In the UTI group, the myeloperoxidase activity was significantly attenuated (P < 0.01), ATP and energy charge were significantly improved (P < 0.01 and P < 0.05, respectively), and the elevation in serum aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase was also markedly suppressed (P < 0.05, P < 0.01, and P < 0.05, respectively) compared with the control group. Sections through the livers of control rats showed severe hepatocyte necrosis with neutrophil infiltration. In the UTI group, there was slight congestion and hepatocyte necrosis. The survival rate after 90-min liver ischemia was significantly improved compared with that in the control group (P < 0.05). The results of this study suggest that pretreatment with UTI significantly attenuates liver reperfusion injury, perhaps by inhibiting neutrophil proteases.

Adenosine Triphosphate↗
PubMed1995

Reflux nephropathy, urinary tract infection, and voiding disorders.

Urinary tract infection (UTI), vesicoureteral reflux (VUR), and certain voiding disorders result in renal damage. In the past few years, the increasing use of 99mTc-dimercaptosuccinic acid renal scans, urodynamic testing, and antenatal sonography have helped shed light on the interrelationship of these disorders. Renal parenchymal involvement during acute febrile UTI and subsequent renal scarring are quite commonly observed in the absence of VUR, suggesting that the presence of reflux is not a prerequisite for renal damage. In infants with gross VUR, renal damage is often present at birth even before the development of any UTI. High intravesical pressures during bladder filling and voiding are commonly observed in infants with gross VUR, reflecting an underlying voiding dysfunction. High voiding detrusor pressures are also commonly observed in infants presenting with symptomatic UTI who do not have VUR. Children with dysfunctional voiding states are at risk for development of VUR and UTI. Renal damage in these children may occur in the absence of one or the other. This review elucidates how voiding dysfunction predisposes children to bacterial colonization of the bladder, the development or perpetuation of VUR, and renal damage.

Humans↗
PubMedDate not supplied

Antibiotic prescribing and outcomes following treatment of symptomatic urinary tract infections in older women.

OBJECTIVE: To describe antibiotic prescribing patterns for the treatment of urinary tract infections (UTI) among older women female long-term care facility residents and evaluate factors associated with adverse outcomes. METHODS STUDY DESIGN: Population-based retrospective cohort study. Population and sampling frame: All female residents of Olmsted County, Minnesota, aged 65 years and older, who were treated for urinary tract infections during calendar year 1996 were included in the study. DATA COLLECTION: Subjects' complete medical records were reviewed and abstracted. Data collected included age, weight, serum creatinine, antibiotic treatment including dosage and duration, as well as retreatment and adverse drug events. RESULTS: A total of 196 subjects, ranging in age from 65 to 98 years, were diagnosed with UTI during calendar year 1996. Forty-four subjects were nursing home residents, and 152 resided in the community. The odds of prolonged antibiotic therapy (7 days or more) were 83 times higher among nursing home residents (Odds ratio = 82.7, 95% Confidence Interval, 11.1-617.7). The odds of receiving treatment for 10 days or longer were 5 times higher among nursing home residents compared to community subjects. The odds of underlying renal impairment necessitating dosage reduction were 3.6 times higher among nursing facility residents. Nursing facility residents were 7.3 times more likely to be treated with excessive dosages of antibiotics, 9.6 times more likely to experience adverse drug events, and 2.6 times more likely to receive retreatment for persistent or recurrent symptoms within one week of antibiotic discontinuation, compared to community subjects with UTI. CONCLUSIONS: Nursing home residents with UTI are treated for longer durations than community elderly. They experience a greater likelihood of receiving antibiotics in excessive dosage, a greater likelihood of adverse drug events, and a greater likelihood of retreatment compared with community subjects with UTI.

Aged↗
PubMed2003

Primary vesicoureteric reflux as a predictor of renal damage in children hospitalized with urinary tract infection: a systematic review and meta-analysis.

Renal parenchymal disease after urinary tract infection (UTI) has been associated with the development of hypertension and renal functional impairment. A systematic literature review and meta-analysis was performed to determine how effectively the finding of primary vesicoureteric reflux (VUR) on micturating cystography (MCU) in children hospitalized with UTI predicted renal parenchymal disease on (99m)Technetium-dimercaptosuccinic acid ((99m)Tc-DMSA) scintigraphy. Medline, Embase, and PubMed were use to find reports with original data for children hospitalized with bacteriologically-proven UTI who had undergone both MCU and (99m)Tc-DMSA scintigraphy, and which also reported both positive and negative results of these tests. A meta-analysis of likelihood ratios positive and negative for MCU was then performed, including tests for heterogeneity. Twelve valid studies were found, seven with data for 537 children, with a positive (99m)Tc-DMSA scan prevalence of 59% overall, and seven studies with data for 1062 kidneys, with a positive (99m)Tc-DMSA scan prevalence of 36%. The likelihood ratio positive for MCU was 1.96 (95% CI, 1.51 to 2.54) for children, and 2.34 (1.53 to 3.57) for kidneys. The likelihood ratio negative was 0.71 (0.58 to 0.85) for children and 0.72 (0.61 to 0.86) for kidneys. There was evidence of heterogeneity. The meta-analysis showed that a positive MCU increases the risk of renal damage in hospitalized UTI patients by about 20%, whereas a negative MCU increases the chance of no renal involvement by just 8%. VUR is hence a weak predictor of renal damage in pediatric patients hospitalized with UTI. Physicians should be aware of the limitations of using MCU-detected primary VUR as an effective screening test for renal damage in this population. Furthermore, the pathogenesis of renal damage in such patients is probably complex because it is often detected without demonstrable VUR.

Child, Hospitalized↗
PubMed2003

Urinary tract infection in very low birth weight preterm infants.

BACKGROUND: The prevalence of urinary tract infection (UTI) in preterm neonates ranges between 4 and 25%. The need for a radiologic investigation has not yet been established in very low birth weight premature newborns (<1500 g birth weight). PATIENTS AND METHODS: For an 11-year period (1990 to 2001), medical records of 62 very low birth weight premature infants admitted to a Level III neonatal intensive care unit and who developed UTI were reviewed retrospectively. Results of renal ultrasound and voiding cystourethrograms were compared between extremely low birth weight infants (birth weight, <1000 g) (Group A, Patient 34) and premature infants with birth weight between 1001 and 1500 g (Group B, Patient 28). RESULTS: UTI was more common in Group A (12.2%) than in Group B (5.7%) infants. Renal ultrasound detected mild renal pelvic dilatation (unilateral or bilateral) in 9 infants in Group A (26%) and in 1 infant in Group B (3.5%). Voiding cystourethrograms were performed in 26 of 34 (76%) infants in Group A and in 17 of the 28 (61%) premature infants in Group B. Vesicourethral reflux (VUR) was observed in 6 infants, 2 in group A (7.7%) and 4 in Group B (23%). CONCLUSIONS: We found that the rate of VUR was lower in very low birth weight premature newborns than that reported in the medical literature among term newborns who developed UTI. VUR was less frequent in extremely low birth weight infants who developed UTI than in infants weighing 1001 to 1500 g.

Female↗
PubMedDate not supplied

Antibiotic prescribing and outcomes following treatment of symptomatic urinary tract infections in older women.

OBJECTIVE: To describe antibiotic prescribing patterns for the treatment of urinary tract infections (UTI) among older women female long-term care facility residents and evaluate factors associated with adverse outcomes METHODS STUDY DESIGN: Population-based retrospective cohort study. Population and sampling frame: All female residents of Olmsted County, Minnesota, aged 65 years and older, who were treated for urinary tract infections during calendar year 1996 were included in the study. DATA COLLECTION: Subjects' complete medical records were reviewed and abstracted. Data collected included age, weight, serum creatinine, antibiotic treatment including dosage and duration, as well as retreatment and adverse drug events. RESULTS: A total of 196 subjects, ranging in age from 65 to 98 years, were diagnosed with UTI during calendar year 1996. Forty-four subjects were nursing home residents, and 152 resided in the community. The odds of prolonged antibiotic therapy (7 days or more) were 83 times higher among nursing home residents (Odds ratio = 82.7, 95% Confidence Interval, 11.1-617.7). The odds of receiving treatment for 10 days or longer were 5 times higher among nursing home residents compared to community subjects. The odds of underlying renal impairment necessitating dosage reduction were 3.6 times higher among nursing facility residents. Nursing facility residents were 7.3 times more likely to be treated with excessive dosages of antibiotics, 9.6 times more likely to experience adverse drug events, and 2.6 times more likely to receive retreatment for persistent or recurrent symptoms within one week of antibiotic discontinuation, compared to community subjects with UTI. CONCLUSIONS: Nursing home residents with UTI are treated for longer durations than community elderly. They experience a greater likelihood of receiving antibiotics in excessive dosage, a greater likelihood of adverse drug events, and a greater likelihood of retreatment compared with community subjects with UTI.

Journal Article↗
PubMed2003

Phase 2 clinical trial of a vaginal mucosal vaccine for urinary tract infections.

PURPOSE: Recurrent urinary tract infections (UTIs) in susceptible women remain a common urological condition. With an increasing number of UTIs being caused by antibiotic resistant bacteria there is a need for alternatives to antibiotics. We determined whether multiple doses of a vaginal mucosal vaccine are effective for increasing long-term resistance to recurrent UTIs. MATERIALS AND METHODS: A total of 54 women were entered into a double-blind, placebo controlled, phase 2 clinical trial using a vaginal vaccine containing 10 heat killed uropathogenic bacteria. Patients were withdrawn from prophylactic antibiotics and randomly assigned to 1 of 3 treatment groups, namely placebo only, primary immunization or primary plus booster immunizations. Subjects received treatments at 0, 1, 2, 6, 10 and 14 weeks. Placebo treated patients received suppositories without bacteria. The primary immunization group received vaccine suppositories, followed by 3 doses of placebo. Patients receiving booster immunizations were given 6 vaccine suppositories. All women were followed for 6 months to determine the time until first recurrence, number of infections and adverse reactions. RESULTS: Women receiving 6 vaccine doses remained free of infections for a significantly longer period than those receiving placebo or primary immunizations. Of patients receiving 6 immunizations 55% did not experience an infection, whereas 89% of placebo treated women had UTIs. No women had significant adverse effects. CONCLUSIONS: This study demonstrates that vaginal mucosal vaccine given for a 14-week period increased the time to re-infection in UTI susceptible women. The infrequent, minimal adverse reactions confirm previous observations on the safety of this vaginal mucosal immunization regimen.

Adult↗
PubMed2004

Dimercapto-succinic acid scintigraphy instead of voiding cystourethrography for infants with urinary tract infection.

PURPOSE: We study the ability of dimercapto-succinic acid (DMSA) scintigraphy to predict the presence of dilating vesicoureteral reflux (VUR) in infants with urinary tract infection (UTI) to simplify the evaluation protocol. MATERIALS AND METHODS: A retrospective analysis of the records of 303 children younger than 2 years with initial UTI investigated with DMSA scintigraphy and voiding cystourethrography (VCU) within 3 months after UTI was performed. RESULTS: In 156 of the 303 children (51%) DMSA scintigraphy showed renal lesions. VUR was found in 80 patients (26%) and VUR grade significantly correlated with the presence of renal lesions. A normal DMSA scintigraphy and dilating VUR (grade III) occurred in 7 infants. At followup after 1 to 2 years, 6 of these 7 patients had normal DMSA scans and 1 had a scarred duplex kidney. VUR resolved spontaneously in 5 and improved spontaneously to grade 1 in 2 patients. None of the 7 children had recurrent UTI. CONCLUSIONS: DMSA scintigraphy in infants with UTI may replace VCU as a first line investigation. A strategy to perform VCU in only patients with renal lesions is proposed. In this study 147 of 303 VCUs would have been unnecessary as only 1 child with a damaged kidney was missed.

Female↗
PubMed2005

Symptomatic refluxing distal ureteral stumps after nephroureterectomy and heminephroureterectomy. What should we do?

PURPOSE: We hypothesize that residual ureteral stumps following nephroureterectomy (NU) or heminephroureterectomy (HNU) are associated with an increased risk of urinary tract infection (UTI) that is decreased by distal ureterectomy. MATERIALS AND METHODS: We performed a retrospective review of 71 patients who underwent NU or HNU for reflux into a nonfunctioning system between 1990 and 2003. The indications for all renal surgery included recurrent UTIs in 44 patients, hypertension in 8 and a combination of these conditions in 19. Voiding cystourethrogram and urine cultures were performed in all patients with recurrent symptomatic UTIs. RESULTS: Followup in all 71 patients averaged 52 months. A total of 11 patients who underwent laparoscopic NU or HNU to the hiatus of the bladder were excluded because they did not have a ureteral remnant. The remaining 60 patients all underwent an open procedure. Of these patients 32 (53%) had refluxing distal ureteral remnants. Six of these 32 patients with refluxing stumps (19%), all girls, became symptomatic during followup. Symptomatic UTIs recurred in these 6 patients an average of 12 times per year (range 8 to 21), which significantly decreased after distal ureterectomy. CONCLUSIONS: If surgery is indicated in patients with reflux into a poorly functioning system, we recommend NU or HNU to the level of the bladder hiatus. If a symptomatic ureteral remnant is present, then distal ureterectomy decreases the rate of symptomatic UTIs in these patients. Laparoscopic distal ureterectomy is a viable surgical technique for this patient population.

Adolescent↗
PubMed2005

Can ultrasonography or uroflowmetry predict which children with voiding dysfunction will have recurrent urinary tract infections?

PURPOSE: It has been suggested that in children with voiding dysfunction improper bladder emptying contributes to recurrent urinary tract infections (UTIs) and progressive renal scarring. Incomplete bladder emptying may be related to bladder-sphincter dyssynergia. Ultrasonography and uroflowmetry are used in the initial evaluation of many children with voiding dysfunction. We determine in children with voiding dysfunction whether incomplete bladder emptying has an important role in the pathogenesis of urinary tract infections and whether abnormal ultrasonography or uroflowmetry can predict which children are at increased risk of recurrent UTIs. MATERIALS AND METHODS: In this retrospective cohort study charts of 148 consecutive patients diagnosed with voiding dysfunction were reviewed for information regarding residual urine volumes on initial post-void ultrasound and the number of urinary tract infections on followup. Initial uroflowmetry curves were blindly reevaluated for this study. RESULTS: Considerable (greater than 10% predicted) post-void residual urine volumes were seen on 15% of ultrasounds, and 78% of uroflowmetry studies were characterized as abnormal. The volume of residual urine (corrected for age) showed a positive correlation with the number of UTIs occurring after the initial visit (r = 0.3, p <0.002). There was no correlation between an abnormal uroflow pattern and number of subsequent UTIs. CONCLUSIONS: Although increased residual urine on post-void ultrasound increases the risk of UTI recurrence in children with voiding dysfunction, it does not allow accurate identification of specific children at risk.

Adolescent↗
PubMed2002

Variations in 10 putative uropathogen virulence genes among urinary, faecal and peri-urethral Escherichia coli.

A total of 868 isolates was screened from seven different collections of organisms from previous studies - pyelonephritis in children aged 1-24 months; first, second and recurring urinary tract infection (UTI) in women aged 18-39 years; UTI in women aged 40-65 years and peri-urethral and faecal isolates from women aged 18-39 years - for the presence of 10 potential Escherichia coli UTI virulence genes. Previously reported differences between the frequency of these genes in UTI compared with faecal isolates were confirmed and extended. A single virulence signature (strains containing aer, kpsMT, ompT, fim and papGAD) occurred in 29% of the pyelonephritic isolates, but in no more than 11% of the other collections. Peri-urethral isolates were found to have frequencies of these 10 genes that differed from those found for both UTI and faecal isolates.

Adolescent↗
PubMed2005

Evaluation of a service development to increase detection of urinary tract infections in children.

RATIONALE, AIMS AND OBJECTIVES: It is suspected that childhood urinary tract infection (UTI) remains under-diagnosed in primary care, and is consequently the cause of subsequent morbidity from renal scarring, hypertension and eventual renal failure. Practice-based education and service developments were undertaken to try to improve the detection of childhood UTI. METHODS: A controlled before-and-after intervention study was conducted. The educational and service developments promoted awareness of and greater testing for UTI among children less than two years of age presenting with febrile illness or other potentially relevant symptoms or signs. Appropriate diagnostic equipment was provided. RESULTS AND CONCLUSIONS: More urine samples were sent by the intervention practices but without a concomitant increase in detection of UTIs. This may indicate that current practice is approaching near maximal detection of UTI in young children.

Education, Medical, Continuing↗