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[Intrauterine defensive mechanism of amniotic fluid and fetal membranes].

To determine the intrauterine defensive role of urinary trypsin inhibitor (UTI), we studied the effects of UTI in amniotic fluid, fetal membranes and myometrium. The level of UTI was 94 +/- 34 U/ml in neonatal urine (compared to adult urine 8.0 +/- 6.0 U/ml) and 88 +/- 37 U/ml in amniotic fluid. This may indicate that the main source of UTI in the amniotic fluid is the fetal urine. UTI was found to be concentrated in vernix, fetal intestine, amniotic membranes and uterine myometrium. Immunostaining of term amnion revealed a dark staining for UTI, whereas in premature deliveries UTI staining was markedly decreased. In myometrium, the concentration of UTI was found to be increased during pregnancy compared to non pregnant myometrium. Also, placentas were well stained for UTI in term pregnancy. Thus UTI has an important role in amniotic fluid, fetal membranes, placenta and uterine muscles. UTI has an inhibitory effect on several enzymes and cytokines. UTI was found to inhibit neutrophil elastase activity as well as trypsin activity. Its inhibitory activity was increased in the presence of lipid. LPS stimulated amnion cells trapped more UTI than unstimulated amnion cells. UTI in amnion cells was released after addition of 1% meconium solution. UTI was also found to inhibit the effect of IL-1, TNF and interleukin-8 on amnion. These results indicate that UTI localized in amnion is important in the protection of fetal membrane especially against bacterial infections and cytokines. It is known that endothelin (ET), prostaglandin F2 alpha (PGF2 alpha) and oxytocin can induce uterine contraction. UTI could inhibit uterine contractions stimulated by ET, PGF2 alpha and oxytocin in isometric contraction test. UTI could also inhibit cervical maturation induced by interleukin-8. Therefore UTI is essential for maintenance of pregnancy. From the isometric contraction tests, we assumed that UTI might works through regulation of calcium entry or availability in the cells. Initial increase in intracellular calcium was also inhibited by UTI pre incubation dose dependantly. We examined the change in intracellular calcium at single cell level by digital image analysis with Fura 2AM as a calcium probe. At resting level UTI incubation did not produce any significant changes in intracellular free calcium. Thrombin, LPS, interleukin-8 and ET-1, known calcium agonists could increase intracellular calcium in fibroblasts, amnion and uterine myocytes. Whereas as the same doses of those known calcium agonists could not change the intracellular free Ca2+ concentrations in UTI pre incubated fibroblasts, amnion cells and uterine smooth muscle cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Abortion, Threatened↗

Recurrence and follow-up after urinary tract infection under the age of 1 year.

In order to analyze the risk factors for recurrence and the value of routine follow-up by monthly urine cultures in a group of children who had their first episode of urinary tract infection (UTI) under 1 year of age, we performed a retrospective survey of 262 children (134 girls, 128 boys) who were treated for their first UTI while aged under 1 year in the Department of Pediatrics, University of Oulu, during the years 1978-1984. Detailed data on these children concerning their first and recurrent UTIs were collected from hospital records using a formulated data sheet. Causative bacteria and vesicoureteral reflux (VUR) were analyzed as possible risk factors for recurrent UTI. The time of recurrence and the possible symptoms during the recurrent UTI were also investigated. The follow-up period after the first UTI was 3 years; 35% of the boys and 32% of the girls contracted a recurrent UTI during the 3-year follow-up. In 86% of cases, the first UTI recurrence occurred within 6 months of the primary UTI. Recurrent UTIs were detected significantly earlier with routine monthly follow-up compared with those seeking treatment because of symptoms (log rank test P < 0.01). There was a significant difference in the number of recurrences of UTI according to the grade of VUR (P = 0.006). Recurrence-free survival was shorter and recurrent UTIs occurred more often in the children with grade 3-5 VUR than in those with grade 0-2 VUR (log rank test P = 0.0005). Children without VUR and children with grade 1-2 VUR did not differ in the recurrence rate, and thus grade 1-2 VUR did not increase the risk for recurrent UTI. Monthly routine urine cultures are efficient in detecting recurrent UTI infections in children. Since grade 3-5 VUR is a risk factor both for increased recurrence rate of UTI and for possible subsequent renal damage, these children should be followed with monthly urine cultures for UTI recurrences if not on preventive medication. Since the vast majority of UTI recurrences occur within 6 months of the first UTI, routine follow-up for 6 months seems to be sufficient after symptomatic UTI in children with grade 3-5 VUR.

Bacterial Infections↗

Identification and characterization of a Kunitz-type protease inhibitor in ascites fluid from patients with ovarian carcinoma.

Urinary trypsin inhibitor (UTI; Mr 40 kDa) is a Kunitz-type protease inhibitor that efficiently inhibits cell-associated trypsin and plasmin activities. The aim of this study is to examine the expression pattern of UTI in the human ovarian carcinoma ascites fluid by Western blotting, zymography, immunoprecipitation, immunohistochemistry, biochemical and gene analyses and animal experiments. We have identified and characterized the 40 kDa immunoreactive UTI (UTI(40)) and 8 kDa degradation fragment (UTI(8)) in ascites fluid. The levels of UTI(40) and UTI(8) are elevated in ascites fluid taken from patients with ovarian carcinoma relative to paired plasma samples. The UTI(40) and UTI(8) were identified immunologically by the reactivity with 2 different anti-UTI antibodies recognizing different epitopes of the UTI molecule, functionally by its ability to bind trypsin and structurally by its apparent molecular mass with and without deglycosylation treatment. The purified polypeptides have been sequenced and were identical with sequences obtained from UTI and the carboxyl-terminal domain of UTI, respectively. However, UTI mRNA was not detected in the ovarian carcinoma tissue and ovarian carcinoma cell lines examined. Based on extravasation experiments using intravenously injected biotinylated inter-alpha-trypsin inhibitor (IalphaI; a precursor of UTI), we conclude that UTI(40) and UTI(8) found in the ascites fluid may result from (i) the extravasation of plasma proteins such as IalphaI into the peritoneal cavity via hyperpermeable vessels and (ii) the subsequent degradation of IalphaI and UTI(40) by tumor cell-associated trypsin-like enzymes.

Adenocarcinoma, Clear Cell↗

Plasma and urine levels of urinary trypsin inhibitor in patients with acute and fulminant hepatitis.

BACKGROUND AND AIM: Urinary trypsin inhibitor (UTI) is synthesized by hepatocytes and excreted into urine. Plasma and urine UTI levels have been measured to evaluate whether these levels may be useful markers in various pathological conditions. However, there has been no study on plasma and urine UTI levels in patients with acute liver diseases. The aim of the present study was to evaluate plasma and urine UTI levels and their relationship with the severity of hepatic damage in patients with acute liver diseases. METHODS: Plasma and urine UTI levels were measured by newly developed enzyme-linked immunosorbent assay in 15 patients with acute hepatitis (AH), 12 patients with acute severe hepatitis (ASH) and 10 patients with fulminant hepatitis (FH), as assessed on admission. The serial changes in plasma and urine UTI were also observed in some patients with AH and ASH. RESULTS: Plasma UTI levels (U/mL, median [25-75th percentile]) were: 11.0, (9.5-16.1) in patients with AH; 7.8 (5.6-11.5) in those with ASH; 6.5 (4.0-9.5) in patients with FH; and 9.7 (7.3-11.0) in normal controls. Plasma UTI levels in patients with FH were significantly lower than in those with AH. Plasma UTI levels showed significant positive correlations with the levels of prothrombin time (PT), hepaplastin test, antithrombin III, alpha2-plasmin inhibitor, plasminogen (Plg) and fibrinogen. After the recovery of liver dysfunction, increased plasma UTI levels in patients with AH were decreased, whereas previously decreased plasma UTI levels in patients with ASH were increased. Urine UTI levels were significantly increased in patients with AH compared with those of normal controls. In patients with ASH and FH, urine UTI levels were increased but not significantly. Urine UTI levels significantly positively correlated with PT and Plg. After the recovery of liver dysfunction, previously increased urine UTI levels in patients with AH were decreased. The correlation between plasma UTI and urine UTI levels was not significant. CONCLUSIONS: The findings of the present study suggested that the levels of plasma and urine UTI changed in patients with AH and were closely related to the abnormalities of coagulo-fibrinolysis, including PT. Further studies are needed to clarify whether these levels may be useful markers to predict the prognosis of acute hepatitis.

Acute Disease↗

Internalization of urinary trypsin inhibitor in human uterine fibroblasts.

We have characterized the molecular species and internalization of urinary trypsin inhibitor (UTI) in human uterine fibroblasts. Link protein (LP) has previously been identified as one of the cell-associated UTI binding proteins. The truncated forms of UTI were readily detectable in the cells after incubating the cells with purified UTI. Immunoblotting analysis with a panel of domain-specific antibodies revealed that the UTI species lacked the amino-terminal domain of UTI, but contained the carboxyl-terminal domain. We have examined whether LP is involved in the UTI internalization in the cells. Internalization of 125I-labelled UTI was blocked by the intact UTI, but not by the carboxyl-terminal domain of UTI. Treatment with a polyclonal antibody to the UTI binding domain of LP partially inhibited UTI binding to the cells, but did not significantly prevent UTI internalization. In addition, preincubation of the cells with hyaluronidase reduced the UTI binding to the cells, but had no effect on the rate with which UTI was internalized. These data allow us to conclude that there are at least two different mechanisms for internalization of UTI. The major one is via unknown UTI receptors in a Ca2+, Mg2+-sensitive manner and another is via LP.

Calcium↗

Recurrent urinary tract infection in women.

Recurrent urinary tract infections (UTI) are common among young healthy women even though they generally have anatomically and physiologically normal urinary tracts. Women with recurrent UTI have an increased susceptibility to vaginal colonization with uropathogens, which is due to a greater propensity for uropathogenic coliforms to adhere to uroepithelial cells. Risk factors for recurrent UTI include sexual intercourse, use of spermicidal products, having a first UTI at an early age, and having a maternal history of UTIs. Inherited factors may be important in some women with recurrent UTI. Many factors thought to predispose to recurrent UTI in women, such as pre- and post-coital voiding patterns, frequency of urination, wiping patterns, and douching have not been proven to be risk factors for UTI. In contrast to the predominantly behavioral risk factors for young women, mechanical and/or physiological factors that affect bladder emptying are most strongly associated with recurrent UTI in healthy postmenopausal women. The management of recurrent UTI is the same as that for sporadic UTI except that the likelihood of infection with an antibiotic resistant uropathogen is higher in women who have received recent antimicrobials. Strategies to prevent recurrent UTI in young women should include education about the association of recurrent UTI with frequency of sexual intercourse and the usage of spermicide-containing products. Continuous or post-coital prophylaxis with low-dose antimicrobials or intermittent self-treatment with antimicrobials have all been demonstrated to be effective in managing recurrent uncomplicated UTIs in women. Estrogen use is very effective in preventing recurrent UTI in post-menopausal women. Exciting new approaches to prevent recurrent UTI include the use of probiotics and vaccines. Further understanding of the pathogenesis of UTI will lead to more effective and safer methods to prevent these frequent infections.

Adolescent↗

Treatment of urinary tract infections among febrile young children with daily intravenous antibiotic therapy at a day treatment center.

OBJECTIVE: Urinary tract infections (UTIs) are common among infants and toddlers. Children can be treated effectively with short courses (2-4 days) of intravenous (IV) therapy followed by oral therapy. If IV therapy is chosen, use of once-daily dosing may allow outpatient management instead of hospital admission. However, no description of ambulatory treatment with IV antibiotics of UTI among febrile children has been reported to date. We aimed to describe the feasibility and complications of outpatient management with IV antibiotics of UTI among febrile children, at the day treatment center (DTC) of a tertiary-care pediatric hospital. METHODS: Between April 1, 2002, and March 31, 2003, a prospective cohort of patients 3 months to 5 years of age who were examined in the emergency department (ED) and diagnosed as having presumed febrile UTI were treated according to a clinical protocol. Patients were treated at the DTC unless they met exclusion criteria, in which case they were hospitalized. The DTC was open 7 days per week, including holidays, from 8:30 am to 4:30 pm. At the DTC, patients were initially treated with a daily dose of IV gentamicin, until the child had been afebrile for at least 24 hours, and with oral amoxicillin, until preliminary urine culture results were available. Children allergic to penicillin received gentamicin only. IV antibiotics were administered through peripheral IV access; the IV catheter's patency was maintained with injection of 50 U of heparin once daily throughout the treatment period. Parental satisfaction with the DTC experience was assessed with an anonymous, self-administered questionnaire. RESULTS: Two hundred ninety-one episodes of presumed febrile UTI were diagnosed in the ED, of which 212 (72.9%) were sent to the DTC. There were 71 hospital admissions (24.4%); in 9 of these instances, the child was admitted because parents refused or were unable to comply with DTC treatment. Adherence to the treatment protocol in the ED was excellent; in 92.1% of presumed febrile UTI episodes (268 of 291 episodes), the patient was referred to the appropriate setting for treatment. In 8 instances, patients who met an exclusion criterion were sent to the DTC. They should have been hospitalized, according to the protocol. At the DTC, a final diagnosis of UTI was made in 178 of the 212 episodes (84%). Patients treated at the DTC, with a final diagnosis of UTI, had a median age of 12.0 months (range: 3-68 months), and their mean initial temperature was 39.2 degrees C (SD: 1.1 degrees C). Patients were afebrile by 24 hours in 52% of UTI episodes and by 48 hours in 82%. Minor problems with IV access occurred in 9.0% of cases. The duration of IV antibiotic therapy at the DTC was 1.9 days (SD: 0.9 day). The mean number of visits to the DTC, including appointments for renal ultrasound and voiding cystourethrography evaluations, was 3.5 (SD: 0.9). Parents were present at all scheduled visits in 98.9% of cases. Four patients needed to be hospitalized from the DTC, but in only 1 case was hospital admission related to UTI treatment. Four patients with UTI treated in the DTC had positive blood cultures, 2 with Escherichia coli (both successfully treated at the DTC) and 2 with contaminants. For 4 children treated at the DTC, UTI was caused by gentamicin-resistant E coli. One patient became afebrile within 24 hours after treatment initiation with IV gentamicin; he was then treated with oral cefixime. A second patient was treated with IV ceftriaxone, administered at the DTC once culture results were available, and remained febrile for <72 hours. The last 2 patients were hospitalized; one, who was also allergic to cephalosporins, had been febrile for 72 hours at the time of hospitalization (once hospitalized, he was treated with IV amikacin), and the other was admitted to the hospital for an unrelated problem, namely, scalp cellulitis. None of these 4 patients was initially bacteremic or became bacteremic during the treatment period. Repeat urine culture was performed within 14 days after treatment initiation in 146 instances, and results were negative in all cases. At telephone follow-up assessments 14 days after discharge, no patient had been rehospitalized because of UTI. Successful treatment at the DTC (defined as attendance at all visits, normalization of temperature within 96 hours, negative control urine cultures, if performed, and absence of hospitalization from the DTC) was observed in 96.6% of the 178 UTI episodes. Overall adherence of physicians to the protocol at the DTC was 87.1% (95% confidence interval: 82.2-92.0%). One hundred seventy-two satisfaction questionnaires were returned and revealed good, very good, or excellent parental satisfaction in 98.8% of cases. CONCLUSIONS: Our data show that ambulatory treatment with IV antibiotics, at a DTC, may be used for at least three-fourths of UTIs among febrile children 3 months to 5 years of age. It is safe and feasible and appears very satisfactory to parents. Although ambulatory treatment with IV antibiotics is more invasive than oral therapy during the initiation of UTI treatment, it ensures almost full compliance, allows close medical supervision, and facilitates investigations related to the UTI. It is an interesting alternative to hospitalization.

Administration, Oral↗

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2000). II. Background of patients].

Five-hundred eighty eight bacterial strains isolated from 435 patients diagnosed as having urinary tract infections (UTIs) in 10 institutions in Japan were supplied between August 2000 and July 2001. Then, the clinical background of patients were investigated such as sex, age, and type of infections, infections and kind of bacteria, frequency of bacteria isolation by age and infections, bacteria and infections by timing of antibiotics administration, and bacteria and infections by surgical procedures. About the relationship between age and sex of patients and type of infections, the number of male patients aged less than 50 years was few, and complicated UTIs without indwelling catheter was the most frequent. In females, the number of patients aged less than 20 years was few. The majority of female patients aged 40 years and over had complicated UTIs while uncomplicated UTIs was most frequent in the patients being twenties. As for type of infections and kind of bacteria, Escherichia coli decreased when the infections became complicated, and pseudomonas aeruginosa increased when the infection became complicated. Enterococcus faecalis was isolated more frequently in complicated UTIs than in uncomplicated UTIs. Considering this result by age of patients, isolated frequency of E. coli was gradually decreased with aging in patients aged 20 years and over with uncomplicated UTIs or complicated UTIs without indwelling catheter. The isolated frequencies of Klebsiella spp., P. aeruginosa, and E. faecalis were high in the patients with complicated UTIs without indwelling catheter. In the patients aged 70 years and over with complicated UTIs with indwelling catheter, P. aeruginosa and E. faecalis were frequently isolated. As for type of causative organisms in UTIs before and after the administration of antibiotics, the isolation of bacteria was remarkably decreased after administration in the patients with uncomplicated UTIs and complicated UTIs without indwelling catheter. E. coli decreased after administration of antibiotics, and P. aeruginosa increased after administration in the patients with all types of infections. As for type of causative organisms in UTIs and surgical procedures, E. coli was frequently isolated in the patients without surgery in all types of infections, while P. aeruginosa was frequently isolated in the patients who underwent surgery. In uncomplicated UTIs, Proteus spp. and E. faecalis were frequently isolated in the patients with surgery. In complicated UTIs without indwelling catheter, Klebsiella spp. was frequently isolated in the patients without surgery and E. faecalis was frequently isolated in the patients with surgery. In complicated UTIs with indwelling catheter, most of organisms except P. aeruginosa and S. aureus were frequently isolated in the patients without surgery.

Adolescent↗

Roles of host and bacterial virulence factors in the development of upper urinary tract infection caused by Escherichia coli.

Aims of this study are to identify host and Escherichia coli virulence factors associated with upper urinary tract infection (UTI) by comparing them with those for lower UTI and determining the association between major predisposing host factors for upper UTI and urovirulence genes for E coli. Host factors and urovirulence genes of E coli associated with bacteremia in patients with upper UTI and their interactions also were studied. One hundred thirty-nine adult patients who fulfilled clinical diagnostic criteria for upper (n = 81) or lower UTI (n = 58) caused by E coli between January 1997 and December 1999 were retrospectively enrolled into this study. Old age (> or =60 years), male sex, diabetes with poor blood glucose control (ie, glycosylated hemoglobin A1C > or = 8.1%), immunosuppression, and urinary tract obstruction were more frequently associated host factors for patients with upper UTI than for those with lower UTI. Using polymerase chain reaction, the papG class II allele was detected more frequently for E coli strains isolated from patients with upper UTI than for those from patients with lower UTI (85% versus 52%; P < 0.0001). Multivariate analysis showed that diabetes with poor blood glucose control, immunosuppression, urinary tract obstruction, and papG class II allele were independently associated with upper UTI. For patients without these three predisposing host factors, the prevalence of papG class II allele was significantly greater in those with upper UTI than those with lower UTI. However, the papG class II allele was less prevalent in strains isolated from patients with upper UTI with urinary tract obstruction or with two of the three predisposing host factors. In addition, both univariate and multivariate analyses showed that old age and papG class II allele were risk factors for the development of E coli bacteremia in patients with upper UTI. In conclusion, both host and E coli virulence factors contribute to the development of upper UTI, and less virulent strains can cause upper UTI in hosts with predisposing factors.

Adhesins, Escherichia coli↗

Prevalence of Candida species in hospital-acquired urinary tract infections in a neonatal intensive care unit.

OBJECTIVE: To determine the prevalence and clinical features of Candida species in hospital-acquired urinary tract infections (UTI) in a neonatal intensive care unit. DESIGN: A retrospective study was conducted of hospital-acquired UTI occurring in infants admitted to a neonatal intensive care unit between January 1, 1989, and June 30, 1995. Hospital-acquired infection was defined as one occurring in an infant who was at least 7 days of age and hospitalized since birth. Urinary tract infection was defined by a urine culture yielding a single organism with > 1000 colony-forming units/ml from a suprapubic aspiration or > 10,000 colony-forming units/ml via urethral catheterization. RESULTS: Fifty-seven infants had 60 UTI during the study period. Candida spp. were responsible for 25 of 60 (42%) UTI. The median gestational age of infants with candidal UTI was 26 weeks (range, 23 to 37) which was significantly less than that for infants with bacterial UTI, 28 weeks (range, 23 to 40) (P = 0.04). Candidemia was present in 13 of 25 (52%) candidal UTI which was significantly more often than bacteremia with bacterial UTI, 3 of 35 (8%) (odds ratio, 11.6; 95% confidence interval, 2.8 to 47.8). The median age of infection for candidal UTI was 34 days (range, 9 to 228), which was significantly earlier than for bacterial UTI, 79 days (range, 7 to 247) (P = 0.003). Renal pelvis fungus balls were present in 7 of 20 (35%) infants with candidal UTI who had renal ultrasound studies. CONCLUSIONS: Candida spp. were the pathogens identified in 42% of hospital-acquired urinary tract infections in a neonatal intensive care unit. Candidemia was associated with 52% of candidal UTI and bacteremia with 8% of bacterial UTI. Candidal UTI occurred significantly earlier than bacterial UTI. Renal fungus balls were present in 35% of infants with candidal UTI.

Bacteremia↗

The effect of the glycosaminoglycan chain removal on some properties of the human urinary trypsin inhibitor.

The major urinary trypsin inhibitor UTI I is a proteoglycan. UTI c (Mr 26,000), produced by chrondroitin lyase digestion of UTI I, was isolated and characterized. About 90% of the glycosaminoglycan chain was removed by this treatment without proteolytic modification, as assessed by amino-acid composition and N-terminal sequence of UTI c. Its electrophoretic mobilities on alkaline and SDS-PAGE are identical with those of UTI II which occurs in urine during storage. To study the role of the glycosaminoglycan chain on the inhibitory properties of UTI I, UTI I and UTI c were compared using different proteinases as target enzymes. The inhibitory activity towards bovine trypsin and chymotrypsin as well as human granulocytic cathepsin G did not differ significantly. However, towards human granulocytic elastase, the equilibrium dissociation constant (Ki) is 5 times higher for UTI c than for UTI I. Weak inhibitory activities were measured on human plasmin, UTI c being more efficient than UTI I. The acid-stability of UTI I is not modified after chrondroitin lyase treatment. UTI I and UTI c are equally sensitive to trypsinolysis indicating that the covalently bound glycosaminoglycan chain does not play an important role for the stability of UTI I.

Cathepsin G↗

Clinical effectiveness and cost-effectiveness of tests for the diagnosis and investigation of urinary tract infection in children: a systematic review and economic model.

OBJECTIVES: To determine the diagnostic accuracy of tests for detecting urinary tract infection (UTI) in children under 5 years of age and to evaluate the effectiveness of tests used to investigate further children with confirmed UTI. Also, to evaluate the effectiveness of following up children with UTI and the cost-effectiveness of diagnostic and imaging tests for the diagnosis and follow-up of UTI in children under 5. An additional objective was to develop a preliminary diagnostic algorithm for healthcare professionals. DATA SOURCES: Electronic databases were searched up to the end of 2002/early 2003. Consultation with experts in the field. REVIEW METHODS: A systematic review was undertaken using published guidelines and results were analysed according to test grouping: diagnosis of UTI and further investigation of UTI. The cost-effectiveness results from existing evaluations were synthesised. A separate cost-effectiveness model was developed using the best available evidence, in part derived from the results of the systematic review, to illustrate the potential cost-effectiveness of some alternative management strategies in a UK setting. The results of the systematic review were used to propose diagnostic algorithms for the diagnosis and further investigation of UTI in children. Economic analyses did not contribute directly to the development of these algorithms. RESULTS: The studies included in the review provided very little data on the accuracy of clinical investigations for the diagnosis of UTI, and criteria for clinical suspicion of UTI were not further defined. The majority of studies included in the review found that clean voided midstream urine (CVU) samples had similar accuracy to suprapubic aspiration (SPA) samples when cultured with the advantage of being a non-invasive collection method that can be used in the GP's surgery. Pad, nappy or bag specimens may be appropriate methods for obtaining a urine sample in non-toilet-trained children, although only limited data were available. Although the glucose test was reported to have the highest accuracy in terms of both ruling in and ruling out disease, only a limited number of studies of this test were included and these were conducted over 30 years ago. Dipstick tests are easy to perform in the GP's surgery, give an immediate result and are relatively cheap. The results of the systematic review showed that a dipstick for leucocyte esterase (LE) and nitrite, where both test results are interpreted in combination, was a good test both for ruling in (both positive) and ruling out (both negative) a UTI. A dipstick positive for either LE or nitrite and negative for the other provides inconclusive diagnostic information and further testing is therefore required in these patients. Microscopy is more time consuming and expensive to perform than a dipstick test, but potentially quicker and cheaper than culture. As with dipstick tests, a combination of microscopy for pyuria and bacteriuria can be used accurately to rule in and rule out a UTI. An indeterminate test result is again obtained if microscopy is positive for either pyuria or bacteriuria, and negative for the other. Confirmatory culture is required in these patients. In patients considered to have a UTI, further culture to determine antibiotic sensitivities may be an option to inform treatment decisions. Only one study satisfied the inclusion criteria of the economic review and the review highlighted a number of potential limitations of this study for NHS decision-making. A separate decision-analytic model was therefore developed to provide a more reliable estimate of the optimal strategy regarding the diagnosis and further investigation of children under 5 with suspected UTI from the perspective of the NHS. The economic model found that the optimal diagnostic strategy for children presenting with symptoms suggestive of UTI depends on a number of key factors. These included the relevant subgroup of children concerned, in terms of gender and age, and the health service's maximum willingness to pay for an additional quality-adjusted life-year. CONCLUSIONS: The results of the systematic review were used to derive an algorithm for the diagnosis of UTI in children under 5. This algorithm represents the conclusions of the review in terms of effective practice. There were insufficient data to propose an algorithm for the further investigation of UTI in children under 5. The quality assessment highlighted several areas that could be improved upon in future diagnostic accuracy studies.

Algorithms↗

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1993). II. Background of patients].

Clinical background was investigated on 734 bacterial strains isolated from patients with urinary tract infections (UTIs) in 10 hospitals during the period from June, 1993 to May, 1994. 1. Distribution of sex, age and infections Among over fifties males, the majority was taken by complicated urinary tract infections. Among females, the uncomplicated urinary tract infections was most frequent without a relation of age. 2. Distribution of sex, age and pathogens isolated from UTIs In uncomplicated UTIs, Escherichia coli was most frequently isolated without a relation of age, and next Klebsiella spp. and CNS. In complicated UTIs without indwelling catheter, E. coli and Enterococcus faecalis were the most frequent. In complicated UTIs with indwelling catheter, Pseudomonas aeruginosa were most frequently isolated, and next E. faecalis. 3. The frequency of complexed infections in UTIs The frequency of complexed infections has increased from in uncomplicated UTIs to complicated UTIs. 4. Administration of antibiotics and pathogens isolated from UTIs In uncomplicated UTIs, pathogens, after administration of antibiotics, isolated from patients have obviously decreased from 222 to 33 isolates. And also, pathogens of complicated UTIs without indwelling catheter, have decreased from 205 to 50 isolates. However, in complicated UTIs with indwelling catheter, pathogens after or before administration of antibiotics, were not revealed an obvious change. 5. Pathogens and UTIs with or without factor and operation In uncomplicated UTIs with or without factor and operation, E. coli was mainly detected. In complicated UTIs without indwelling catheter and with or without factor and operation, E. coli and E. faecalis were mainly detected. In complicated UTIs with indwelling catheter and with factor and operation, P. aeruginosa and E. faecalis were mainly detected, 22.0% and 14.1%, respectively. Without factor and operation, was detected, E. faecalis 21.1%, and next Proteus spp. 15.8%. The distribution of pathogens, in the case of Serratia spp., has been obviously varied by the influence of factor and operation.

Adolescent↗

A longitudinal cohort study of elderly women with urinary tract infections.

AIMS: the prevalence of urinary tract infections (UTI), urinary incontinence (UI), estrogen-use and overall mortality in a cohort of elderly women who had been treated for UTI in 1985-86 was re-assessed 10 years later. MATERIAL AND METHODS: a random sample of 6000 women from the birth cohorts 1900, 1905, 1910, 1915 and 1920 were invited in 1986 to complete a questionnaire about UTI, UI and estrogen use (response rate 70%; n = 4206). Treatment with antibiotics for UTI during 1985-86 was reported by 688 (17%) women. In 1995 a similar questionnaire was sent to the women from this group who were still alive (n = 434). Mortality in the women with a history of UTI was compared with an aged-matched control group of women who did not have UTI during 1985-86. RESULTS: the questionnaire was completed and returned by 361 (83%) women. Treatment for at least one UTI during the last 9 years was reported by 219 (61%) women. The number of episodes varied: 35% had one to two UTI, 28% had three to four UTI, 27% five to ten UTI and 10% had had more than 10 UTI. In 1986, the prevalence of UI was higher in women with a history of UTI than in the total population sample (30 vs. 17%; P < 0.001). The prevalence of UI had increased from 30% in 1986 to 33% in 1995 (P < 0.05). Mortality in the women with a history of UTI was higher than in the aged-matched control group (37 vs. 28%; P < 0.001). A total of 162 (45%) women had received estrogen therapy at some time after the age of 60 years and 140 (39%) reported that they were currently taking low potency estrogens. CONCLUSION: elderly women with a history of UTI had a continued high occurrence of UTI and UI, and overall mortality was higher in these women than in an age-matched control group of women from the total population.

Age Factors↗

Identity of urinary trypsin inhibitor-binding protein to link protein.

Urinary trypsin inhibitor (UTI), a Kunitz-type protease inhibitor, directly binds to some types of cells via cell-associated UTI-binding proteins (UTI-BPs). Here we report that the 40-kDa protein (UTI-BP(40)) was purified from the cultured human chondrosarcoma cell line HCS-2/8 by UTI affinity chromatography. Purified UTI-BP(40) was digested with trypsin, and the amino acid sequences of the peptide fragments were determined. The sequences of six tryptic fragments of UTI-BP(40) were identical to subsequences present in human link protein (LP). Authentic bovine LP and UTI-BP(40) displayed identical electrophoretic and chromatographic behavior. The UTI-binding properties of UTI-BP(40) and LP were indistinguishable. Direct binding and competition studies strongly demonstrated that the NH(2)-terminal fragment is the UTI-binding part of the LP molecule, that the COOH-terminal UTI fragment (HI-8) failed to bind the NH(2)-terminal subdomain of the LP molecule, and that LP and UTI-BP(40) exhibited significant hyaluronic acid binding. These results demonstrate that UTI-BP(40) is identical to LP and that the NH(2)-terminal domain of UTI is involved in the interaction with the NH(2)-terminal fragment of LP, which is bound to hyaluronic acid in the extracellular matrix.

Aggrecans↗

Risk factors for second urinary tract infection among college women.

To better understand the etiology of recurrent urinary tract infection (UTI), the authors followed a cohort of 285 female college students with first UTI for 6 months or until second UTI. A first UTI due to Escherichia coli was followed by a second UTI three times more often than was a non-E. coli first UTI (24 vs. 8%; p = 0.02). In a logistic regression analysis limited to the 224 women from the University of Michigan Health Service and the University of Texas at Austin Health Service from September 1992 to December 1994, with a first UTI due to E. coli, vaginal intercourse increased the risk of a second UTI with both a different (odds ratio (OR) = 1.60, 95% confidence interval (CI): 1.19, 2.15) and the same (OR = 1.37, 95% CI: 0.91, 2.07) uropathogen, as did using a diaphragm, cervical cap, and/or spermicide (same uropathogen: OR = 1.53, 95% CI: 0.95, 2.47; different uropathogen: OR = 1.77, 95% CI: 1.22, 2.58). Condom use decreased the risk of a second UTI caused by a different uropathogen (OR = 0.68, 95% CI: 0.48, 0.99) but had no effect on a second UTI caused by the same E. coli (OR = 0.99; 95% CI: 0.66, 1.50). Type or duration of treatment was not associated with a second UTI. Although the risk of second UTI is strongly influenced by sexual behavior, women with a first UTI caused by E. coli are more likely than are those with a non-E. coli first UTI to have a second UTI within 6 months.

Adolescent↗

A pilot randomized double-blind placebo-controlled trial on the use of antibiotics on urinary catheter removal to reduce the rate of urinary tract infection: the pitfalls of ciprofloxacin.

OBJECTIVE: To assess if a short course of antibiotics starting at the time of the removing a short-term urethral catheter decreases the incidence of subsequent urinary tract infection (UTI). PATIENTS AND METHODS: Patients across specialities with a urethral catheter in situ for >/= 48 h and </= 7 days were recruited at the time of catheter removal. Patients were excluded if they had had recent genitourinary surgery or were on antibiotics. Eligible patients were randomly assigned to a 48-h course of either ciprofloxacin or placebo tablets starting 2 h before catheter removal. A catheter specimen of urine was obtained before the start of the trial medication. The follow-up was at 7 and 14 days after catheter removal, with a questionnaire for UTI symptoms, and a mid-stream urine sample was taken. RESULTS: Forty-eight patients were recruited and had a complete follow-up (25 received ciprofloxacin and 23 placebo). Of the ciprofloxacin group, four patients (16%) had a UTI at the follow-up after catheter removal, and two were symptomatic. The UTI in two patients (including one of those symptomatic) was newly developed after catheter removal; the other two UTIs were a result of failure to resolve a catheter-associated UTI. All these UTIs in the ciprofloxacin group were resistant to ciprofloxacin. Of the placebo group, three patients (13%) had a UTI at the follow-up after removal, and one patient was symptomatic. The UTI, newly developed after catheter removal, was resistant to ciprofloxacin. The other two patients were asymptomatic; their UTIs were a result of failure to resolve a catheter-associated UTI, and one was resistant to ciprofloxacin. CONCLUSIONS: The risk of UTI (both symptomatic and asymptomatic) after removing a urethral catheter is real, even in absence of catheter-associated UTI before removal. UTIs occurring after removing a short-term urinary catheter had a high rate of resistance to ciprofloxacin. There was no detectable significant benefit in using prophylactic ciprofloxacin to reduce the UTI rate after catheter removal.

Adolescent↗

The association between indwelling urinary catheter use in the elderly and urinary tract infection in acute care.

BACKGROUND: The use of indwelling urinary catheters (IUCs) is thought to be the most significant risk factor for developing nosocomial urinary tract infections (UTIs). However, it is unclear how many elderly patients have preexisting bacteriuria prior to IUC placement. The purpose of this study was to determine 1) the frequency and appropriateness of IUC use in the Emergency Department (ED) in elderly patients admitted to our acute care hospital, 2) the percentage of elderly patients with an IUC who were discharged from the hospital with a diagnosis of UTI, 3) the percentage of patients with IUCs who were diagnosed and treated for UTI in the ED or who had admission bacteriuria > or =105 organisms/ml indicating preexisting UTI, and 4) the percentage of patients with no indication of UTI on admission who had inappropriately placed IUCs and subsequently were diagnosed with a UTI. METHODS: Retrospective chart review. Chi square used to test significance of differences in proportions. RESULTS: Seventy three percent of patients who received an IUC in the ED were elderly (> or =65 years old). During the study period, 277 elderly patients received an IUC prior to admission. Of these, 77 (28%) were diagnosed with UTI during their hospitalization. Fifty three (69%) of those diagnosed with a UTI by discharge either had the UTI diagnosed in the ED or had bacteriuria > or =105 organisms/ml prior to IUC placement. Of the 24 elderly patients who developed a catheter-associated UTI (i.e., 9% of the elderly population who received an IUC), 11 of the IUCs were placed inappropriately. Thus, 4% of elderly patients with no indication of UTI on admission who received an inappropriate IUC in the ED had a primary or secondary diagnosis of UTI by discharge. The overall rate of nosocomial UTI due to an inappropriately placed IUC was the same in males and females. CONCLUSION: This study indicates that the strong association between IUC use and UTI may be partly explained by the high prevalence of preexisting UTI prior to IUC placement. Further prospective studies are needed to clarify the true risk vs benefit ratio for IUC use in acutely ill elderly patients.

Aged↗