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PubMed1995

Inhibition of tumor cell invasion through matrigel by a peptide derived from the domain II region in urinary trypsin inhibition.

Urinary trypsin inhibitor (UTI) has a multipotent inhibitory effect on proteases such as trypsin, chymotrypsin, plasmin, human leukocyte elastase, or hyaluronidase. UTI can bind easily to its receptors on various types of tumor cells (human ovarian cancer HOC-I cells, human choriocarcinoma SMT-cc1 cells, and murine Lewis lung carcinoma 3LL cells). Our results show that the UTI receptors of some tumor cells have a possible role in modulating plasmin activity on the cell surface and prevention of tumor cell invasion and metastasis (H. Kobayashi et al., J. Biol. Chem., 269; 20642-20647, 1994). UTI interacts with tumor cells as a negative modulator of the invasive cells. We investigated whether this effect may be mediated by UTI binding to the cell surface receptors. In addition, the role of peptide sequences from each UTI domain and their interaction with tumor cells were investigated. UTI derivatized with biotin or FITC was taken up by tumor cells in a dose-dependent manner. This cell association was inhibited with a monoclonal antibody D1, which specifically recognizes NH2 terminus (domain I) of UTI. The binding was inhibited by fluid phase UTI, but not HI-8, COOH terminus (domain II) of UTI, suggesting that UTI binds to cells through a site in the UTI domain I. Furthermore, we found that UTI, HI-8 and a number of peptides containing Arg-Gly-Pro-Cys-Arg-Ala-Phe-Ile promoted the inhibition of tumor cell invasion. This site corresponds to the plasmin-inhibiting domain within HI-8. The possibility that UTI binding to tumor cells might be involved in the prevention of tumor cell invasion in vitro was excluded since HI-8, lacking domain I, promotes the inhibition of tumor cell invasion with essentially the same affinity as UTI. All these data allow us to conclude that inhibition of tumor cell invasion is mediated by domain II, which possesses anti-plasmin activity.

Amino Acid Sequence↗
PubMed2002

Epidemiology of urinary tract infections: incidence, morbidity, and economic costs.

Urinary tract infections (UTIs) are considered to be the most common bacterial infection. According to the 1997 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, UTI accounted for nearly 7 million office visits and 1 million emergency department visits, resulting in 100,000 hospitalizations. Nevertheless, it is difficult to accurately assess the incidence of UTIs, because they are not reportable diseases in the United States. This situation is further complicated by the fact that accurate diagnosis depends on both the presence of symptoms and a positive urine culture, although in most outpatient settings this diagnosis is made without the benefit of culture. Women are significantly more likely to experience UTI than men. Nearly 1 in 3 women will have had at least 1 episode of UTI requiring antimicrobial therapy by the age of 24 years. Almost half of all women will experience 1 UTI during their lifetime. Specific subpopulations at increased risk of UTI include infants, pregnant women, the elderly, patients with spinal cord injuries and/or catheters, patients with diabetes or multiple sclerosis, patients with acquired immunodeficiency disease syndrome/human immunodeficiency virus, and patients with underlying urologic abnormalities. Catheter-associated UTI is the most common nosocomial infection, accounting for >1 million cases in hospitals and nursing homes. The risk of UTI increases with increasing duration of catheterization. In noninstitutionalized elderly populations, UTIs are the second most common form of infection, accounting for nearly 25% of all infections. There are important medical and financial implications associated with UTIs. In the nonobstructed, nonpregnant female adult, acute uncomplicated UTI is believed to be a benign illness with no long-term medical consequences. However, UTI elevates the risk of pyelonephritis, premature delivery, and fetal mortality among pregnant women, and is associated with impaired renal function and end-stage renal disease among pediatric patients. Financially, the estimated annual cost of community-acquired UTI is significant, at approximately $1.6 billion.

Adolescent↗
PubMed2003

Epidemiology of urinary tract infections: incidence, morbidity, and economic costs.

Urinary tract infections (UTIs) are considered to be the most common bacterial infection. According to the 1997 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, UTI accounted for nearly 7 million office visits and 1 million emergency department visits, resulting in 100,000 hospitalizations. Nevertheless, it is difficult to accurately assess the incidence of UTIs, because they are not reportable diseases in the United States. This situation is further complicated by the fact that accurate diagnosis depends on both the presence of symptoms and a positive urine culture, although in most outpatient settings this diagnosis is made without the benefit of culture. Women are significantly more likely to experience UTI than men. Nearly 1 in 3 women will have had at least 1 episode of UTI requiring antimicrobial therapy by the age of 24 years. Almost half of all women will experience 1 UTI during their lifetime. Specific subpopulations at increased risk of UTI include infants, pregnant women, the elderly, patients with spinal cord injuries and/or catheters, patients with diabetes or multiple sclerosis, patients with acquired immunodeficiency disease syndrome/human immunodeficiency virus, and patients with underlying urologic abnormalities. Catheter-associated UTI is the most common nosocomial infection, accounting for >1 million cases in hospitals and nursing homes. The risk of UTI increases with increasing duration of catheterization. In noninstitutionalized elderly populations, UTIs are the second most common form of infection, accounting for nearly 25% of all infections. There are important medical and financial implications associated with UTIs. In the nonobstructed, nonpregnant female adult, acute uncomplicated UTI is believed to be a benign illness with no long-term medical consequences. However, UTI elevates the risk of pyelonephritis, premature delivery, and fetal mortality among pregnant women, and is associated with impaired renal function and end-stage renal disease among pediatric patients. Financially, the estimated annual cost of community-acquired UTI is significant, at approximately $1.6 billion.

Adolescent↗
PubMed1981

Immunochemical studies of human urinary trypsin inhibitor.

Antisera against purified urinary trypsin inhibitor (UTI-I, molecular weight 67,000) and UTI-III (molecular weight 23,000) were first produced in rabbits. Both anti-UTI-I and anti-UTI-III sera formed a single immunoprecipitin line with human plasma inter-alpha-trypsin inhibitor (I alpha TI), whereas two immunoprecipitin lines were formed with crude urine. It was speculated that both UTI-I and UTI-II might be present in normal human urine. In the present study, the inhibitory effects of anti-UTI sera on UTI activity were examined by three different assay methods. The results indicated that the inhibitory effect was almost immediate. Although the inhibitory effect of anti-UTI-III serum on UTI-III was almost of the same degree of completeness for the three assay methods. UTI-I was partially inhibited by the anti-UTI-I serum when residual trypsin activity was measured by the caseinolytic or fibrinolytic assay method. This discrepancy was considered to be due to the difference in conformational change between UTI-I and UTI-III by antigen-antibody reaction.

Alpha-Globulins↗
PubMed2000

Newborn circumcision decreases incidence and costs of urinary tract infections during the first year of life.

OBJECTIVE: To assess the effect of newborn circumcision on the incidence and medical costs of urinary tract infection (UTI) during the first year of life for patients in a large health maintenance organization. SETTING: Kaiser Permanente Medical Care Program of Northern California (KPNC). PATIENTS: The population consisted of members of KPNC. The study group consisted of a cohort of 28 812 infants delivered during 1996 at KPNC hospitals; of the 14 893 male infants in the group, 9668 (64.9%) were circumcised. A second cohort of 20 587 infants born in 1997 and monitored for 12 months was analyzed to determine incidence rates. DESIGN: Retrospective study of all infants consecutively delivered at 12 facilities. OUTCOME MEASURES: Diagnosis of UTI was determined from the KPNC computerized database using the International Classification of Diseases, Ninth Revision code for inpatients and KPNC Outpatient Summary Clinical Record codes for outpatients. A sample of 52 patient charts was reviewed to confirm the International Classification of Diseases, Ninth Revision and KPNC Outpatient Summary Clinical Record codes and provide additional data. RESULTS: Infants <1 year old who were born in 1996 had 446 UTIs (292 in females; 154 in males); 132 (86%) of the UTIs in males occurred in uncircumcised boys. The mean total cost of managing UTI was 2 times as high in males ($1111) as in females ($542). This higher total cost reflected the higher rate of hospital admission in uncircumcised males with UTIs (27.3%) compared with females (7.5%); mean age at hospitalization for UTI was 2.5 months old for uncircumcised boys and 6.5 months old for girls. In 1996, total cost of managing UTI in uncircumcised males ($155 628) was 10 times higher than for circumcised males ($15 466) despite the fact that uncircumcised males made up only 35.1% of the male patient base in 1996, reflecting the more frequent occurrence of UTI in uncircumcised males (132 episodes) than in circumcised males (22 episodes), and the larger number of hospital admissions in uncircumcised males (38) than in circumcised males (4). The incidence of UTI in the first year of life was 1:47 (2.15%) in uncircumcised males, 1:455 (.22%) in circumcised males, and 1:49 (2. 05%) in females. The odds ratio of UTI in uncircumcised:circumcised males was 9.1:1. CONCLUSIONS: Newborn circumcision results in a 9. 1-fold decrease in incidence of UTI during the first year of life as well as markedly lower UTI-related medical costs and rate of hospital admissions. Newborn circumcision during the first year of life is, thus, a valuable preventive health measure, particularly in the first 3 months of life, when uncircumcised males are most likely to be hospitalized with severe UTI.

California↗
PubMed2001

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1999). II. Background of patients].

Five-hundred forty four bacterial strains isolated from 412 patients diagnosed as having urinary tract infections (UTIs) in 9 institutions in Japan were supplied between the period of August 1999 to July 2000. Then, the clinical background of patients were investigated such as sex, age and type of infections, infections and kind of bacteria, frequency of isolation of bacteria by age and infections, bacteria and infections by timing of administration of antibiotics, 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. Complicated UTIs without indwelling catheter was the most frequent among female patients aged between 40 to 59 years, in other age groups, uncomplicated UTIs was most frequent. As for type of infections and kind of bacteria, Escherichia coli decreased when the infections became complicated, and Pseudomonas aeruginosa and Enterococcus faecalis increased when the infection became complicated. Considering this result by age of patients, isolation frequency of E. coli was gradually decreased with aging in patients aged more than 20 years with uncomplicated UTIs or complicated UTIs without indwelling catheter. The isolation frequencies of E. faecalis and Staphylococcus aureus were gradually increased with aging in complicated UTIs without indwelling catheter. In patients with complicated UTIs with indwelling catheter, there was no difference between age group, and 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 patients with uncomplicated UTIs and complicated UTIs without indwelling catheter. E. coli decreased after administration of antibiotics, and P. aeruginosa and E. faecalis increased after administration in patients with all infections. As for type of causative organisms in UTIs and surgical procedures, E. coli were more frequently isolated in patients with uncomplicated UTIs when surgical procedures were experienced. Also, Klebsiella spp. and E. faecalis were more frequently isolated in patients with surgical procedures. However, in complicated UTIs, type of causative organisms had no relationship with surgical procedures.

Adolescent↗
PubMed2003

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2001). II. Background of patients].

Five-hundred thirty one bacterial strains isolated from 412 patients diagnosed as having urinary tract infections (UTIs) in 10 institutions in Japan were supplied between September and December 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. With regard to the relationship between age and sex of patients and type of infections, the number of cases aged lower than 50 years was few and complicated UTIs without indwelling catheter was the most frequent in male patients. In females, the number of patients aged lower than 20 years was few. Most of female patients aged lower than 80 years had uncomplicated UTIs. As for the relationship between type of infections and kind of bacteria, Escherichia coli decreased as the infections were more complicated, and Pseudomonas aeruginosa and Enterococcus faecalis increased as the infections were more complicated. In relation of these results to age of patients, isolation frequency of E. coli gradually decreased with aging in patients aged 20 years and older with uncomplicated UTIs. The isolation frequencies of E. faecalis decreased with aging in the patients with complicated UTIs without indwelling catheter while P. aeruginosa decreased with aging in the patients with complicated UTIs with indwelling catheter. E. coli was isolated a few after administration of antibiotics, and P. aeruginosa and E. faecalis were frequently isolated after administration in the patients with all types of infections. As for type of causative organisms in UTIs and with or without surgical operation, E. coli was frequently isolated in the patients without surgery in the patients with uncomplicated UTIs and complicated UTIs without indwelling catheter, while P. aeruginosa was frequently isolated in the patients who underwent surgery in the patients with uncomplicated UTIs and complicated UTIs with indwelling catheter. In uncomplicated UTIs, isolation frequencies of Klebsiella spp., P. aeruginosa, and E. faecalis were significant in the patients with surgery. In complicated UTIs without indwelling catheter, Klebsiella spp. was frequently isolated in the patients with surgery. In complicated UTIs with indwelling catheter, S. aureus and Staphylococcus spp. were frequently isolated in the patients without surgery.

Adolescent↗
PubMed2004

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2002). II. Background of patients].

A total of 615 bacterial strains isolated from 491 patients diagnosed as having urinary tract infections (UTIs) in 13 institutions in Japan were supplied between August 2002 and July 2003. Then, the clinical background of patients were investigated such as sex, age, and type of 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. The bacterial strains were divided by the age and sex of the patients and the types of infections. In males, the number of patients aged less than 50 years was few and the complicated UTIs without indwelling catheter was observed most frequently. In the present time, the bacteria most frequently isolated were Escherichia coli. Pseudomonas aeruginosa and Enterococcus faecalis were also relatively frequently isolated. E. coli decreased and P. aeruginosa increased with the complication of the infections. E. faecalis tended to be isolated more frequently in the complicated UTIs than in the uncomplicated UTIs. With respect to the relation of these results to the age of the patients, in the uncomplicated UTIs, the isolation frequency of E. coli was the highest in all age groups, accounting for 70.8% in 20-49 years old. In the complicated UTIs without indwelling catheter, the isolation frequency of E. coli decreased with aging of the patients and was lower than that of E. faecalis in the patients aged 70 or more (18.3 vs 20.6%). In the complicated UTIs with indwelling catheter, the isolation frequency of E. coli was lower than in the uncomplicated UTIs in all age groups and P. aeruginosa and E. faecalis were more frequently isolated. In comparison of causative bacteria in UTIs between before and after the administration of antibiotics, E. coli decreased and P. aeruginosa increased after the administration in any UTIs. In comparison of causative bacteria in UTIs with or without surgery, E. coli was more frequently isolated in the patients without surgery, while P. aeruginosa was more in the patients with surgery in any UTIs. E. faecalis was more frequently isolated in the patients with surgery in uncomplicated and complicated UTIs without indwelling catheter and in the patients without surgery in complicated UTIs with indwelling catheter.

Age Factors↗
PubMed1994

Characterization of the cellular binding site for the urinary trypsin inhibitor.

A highly purified urinary trypsin inhibitor (UTI) inhibits not only tumor cell invasion in an in vitro assay but also production of experimental and spontaneous lung metastasis in an in vivo mouse model. UTI is present both in the lysate of tumor cells (human choriocarcinoma SMT-cc1 cells, human promyeloid leukemia U937 cells, and murine Lewis lung carcinoma 3LL cells) and human neutrophils. In each medium from tumor cells, most of the cell-associated UTI is on the cell surface. Cell-binding experiments employing cell enzyme-linked immunosorbent assay and flow cytometry indicated that tumor cells (SMT-cc1 and 3LL cells) have specific binding sites for UTI on their cell surface. UTI binds rapidly and with relatively high affinity to SMT-cc1 and 3LL cells. UTI is bound to a specific surface receptor that is incompletely saturated. U937 cells and neutrophils did not show any specific binding to UTI, since UTI receptors on the cell surface of U937 cells and neutrophils were completely saturated with endogenous UTI. UTI forms yielded cross-linked 150- and 80-kDa ligand receptor complexes with cultured SMT-cc1 cells, suggesting molecular masses of 110 and 40 kDa for the UTI receptors. Purification of the two UTI receptor proteins by ligand affinity chromatography (ligand-blotting analysis) yielded two bands when analyzed by SDS-polyacrylamide gel electrophoresis, corresponding in electrophoretic mobility to those calculated by cross-linking analysis. The results reported here showing that some tumor cells carry UTI receptors are in line with a possible role of surface-bound UTI in modulating plasmin activity to the close environment of the cell surface and in processes like prevention of tumor cell invasion and metastasis.

Animals↗
PubMed1996

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1994). II. Background of patients].

Clinical background was investigated on 628 bacterial strains isolated from patients with urinary tract infections (UTIs) in 10 hospitals during period from June, 1994 to May, 1995. 1. Distributions of sex, age and urinary tract infections Among over sixties 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. As for over 40 females, the increase of complicated UTI was admitted. 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 Enterococcus faecalis and CNS. In complicated UTIs without indwelling catheter, E. coli, Pseudomonas aeruginosa and E. faecalis were isolated the most frequent. In complicated UTIs with indwelling catheter, P. aeruginosa was most frequently isolated, and next E. faecalis and Staphylococcus aureus. 3. Administration of antimicrobial agents and pathogens isolated from UTIs In uncomplicated UTIs, pathogens, after administration of antibiotics, isolated from patients have obviously decreased from 216 to 32 isolates. And also, pathogens of complicated UTIs without indwelling catheter, have decreased from 127 to 50 isolates. However, in complicated UTIs with indwelling catheter, pathogens after or before administration of antibiotics, were not revealed an obvious change. 4. 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 factor and operation E. faecalis was mainly detected, and next E. coli, S. aureus and P. aeruginosa. Without factor and operation, E. coli was mainly detected. In complicated UTIs with indwelling catheter and with factor and operation, P. aeruginosa, E. faecalis and S. aureus were mainly detected at 23.5%, 15.0%, 15.0%, respectively. Without factor and operation, Proteus spp. 22%, and next E. faecalis and P. aeruginosa 10% and 12%, were detected, respectively. The distribution of pathogens, in the case of Proteus spp. and P. aeruginosa has been obviously varied by the influence of factor and operation.

Adolescent↗
PubMed1998

Urinary trypsin inhibitor, a Kunitz-type protease inhibitor, modulates tumor necrosis factor-stimulated activation and translocation of protein kinase C in U937 cells.

Urinary trypsin inhibitor (UTI) is a Kunitz-type protease inhibitor. We have reported that UTI inhibited TNF-induced urokinase (uPA) production via a protein kinase C (PKC)-dependent mechanism. It is likely that UTI suppresses tumor cell invasion and metastasis by a mechanism, possibly by inhibiting uPA production. In the present study, we attempted to determine how UTI is associated with PKC, and how UTI is involved in uPA-dependent tumor cell invasion and metastasis. The increments of membrane-associated PKC activity by TNF were subsequently accompanied by a rapid loss of cytosol-associated PKC activity in U937 leukemia cells. Semi-quantitative immunoblotting of membrane and cytosol fractions showed that the translocation of PKC-alpha, -beta, and -epsilon were blocked by the addition of UTI in cells stimulated with TNF but not in cells stimulated with PMA, demonstrating that PKC itself is not sensitive to UTI. This effect was dependent on the carboxyl-terminus of UTI. In addition, UTI neither inhibited TNF binding to cellular receptors nor inactivate PKC and uPA activities directly. Taken together, the experiments suggest that the carboxyl-terminus of UTI may inhibit the PKC-signalling pathways upstream of diacylglycerol by a mechanism, possibly by interrupting the coupling of receptor and effector systems. UTI was shown to have an interesting new function besides being a protease inhibitor. This is the first report that UTI has a selective inhibition of TNF-activated PKC. We conclude that UTI suppresses tumor cell invasion and metastasis by a mechanism that UTI inhibits TNF-stimulated uPA production via a PKC-dependent mechanism.

Blotting, Western↗
PubMed2001

Reliability of the urinalysis for predicting urinary tract infections in young febrile children.

BACKGROUND: Urinary tract infections (UTIs) are a common source of bacterial infection among young febrile children. Clinical variables affecting the sensitivity of the urinalysis (UA) as a screen for UTI have not been previously investigated. The limited sensitivity of the UA for detecting a UTI requires that a urine culture be obtained in some children regardless of the UA result; however, a proper urine culture requires an invasive procedure, so the criteria for its use should be optimized. OBJECTIVES: To determine how the sensitivity of the standard UA as a screening test for UTI varies with age, and to determine the clinical situation that necessitates the collection of a urine culture regardless of the UA result. METHODS: Retrospective medical record review of patients younger than 2 years with fever (>/=38 degrees C) seen in the emergency department during a period of 65 months. All urine cultures were reviewed for the collection method, isolates, and colony counts. A UA result was considered positive if the presence of 1 of the following was detected: leukocyte esterase, nitrite, or pyuria (>/=5 white blood cells per high power field). Patients who had a paired UA and urine culture were used to calculate the sensitivity, specificity, and likelihood ratios of the UA. The prevalence of UTIs was also subcategorized by age, race, sex, and fever. RESULTS: Medical records of 37 450 febrile children younger than 2 years were reviewed. Forty-four percent were girls. Median age and temperature were 10.6 months and 38.8 degrees C. A total of 11 089 patients (30%) had urine cultures obtained. The sensitivity of the UA was 82% (95% confidence interval [CI], 79%-84%) and did not vary by age subgroups. The specificity of UA was 92% (95% CI, 91%-92%). The likelihood ratios for a positive UA and negative UA were 10.6 (95% CI, 10.0-11.2) and 0.19 (95% CI, 0.18-0.20), respectively. Prevalence of UTI was 2.1% overall (2.9% for girls and 1.5% for boys, respectively). Among girls, the prevalence of UTI was 5.0% in white patients, 2.1% in Hispanic patients, and 1.0% in black patients. Among boys, the prevalence was 2.2% in Hispanic patients, 1.4% in white patients, and 0.8% in black patients. Higher prevalence was also seen among patients with a temperature at or above 39 degrees C compared with those whose temperature was between 38.0 degrees C and 38.9 degrees C. The greatest prevalence of UTI (13%) was found among white girls younger than 6 months with a temperature at or greater than 39 degrees C. The posttest probability of a UTI in the presence of a negative UA can be calculated using the negative likelihood ratio and the patient-specific prevalence of UTI. When the prevalence of UTI is 2%, 1 UA among 250 will produce a false-negative test result. CONCLUSIONS: The sensitivity of the standard UA is 82% (95% CI, 79%-84%) and does not vary with age in febrile children younger than 2 years. The prevalence of UTI varies by age, race, sex, and temperature. A negative likelihood ratio and estimates of prevalence can be used to calculate the risk of missing a UTI due to a false-negative UA result.

Black or African American↗
PubMed2004

Children with a febrile urinary tract infection and a negative radiologic workup: factors predictive of recurrence.

OBJECTIVES: To determine the recurrence rate and risk factors for urinary tract infection (UTI) in children who present with a febrile UTI and have a negative radiologic evaluation. Febrile UTIs with no urinary tract abnormalities are a common cause of morbidity in children. METHODS: We performed a retrospective review of all children referred to our medical center after a febrile UTI. RESULTS: We reviewed 850 charts. Of 850 children, 78 had had a febrile UTI and normal ultrasound and voiding cystourography findings. Of the 78 children, 25 had had a recurrent UTI (3 boys and 22 girls). Forty-five percent of the girls with a febrile UTI developed a recurrent UTI and 14% of the boys had a recurrent UTI (P = 0.02). Three boys (two younger than 1 year of age) were uncircumcised and had one recurrent febrile UTI. Eleven (39%) of 28 girls who first presented at younger than 1 year of age and 7 (58%) of 12 girls who presented at 5 years of age or older had recurrent UTIs. The recurrence rate in the 2 to 5-year-old age group was 24% (4 of 17). Seven of the older girls exhibited symptoms of dysfunctional elimination syndrome. CONCLUSIONS: In children with a febrile UTI and a negative radiologic evaluation, recurrence was more common in girls. Boys who were uncircumcised may be at an increased risk of infection during the first year of life. In girls, the age at the time of the first infection was not predictive of recurrence. Although dysfunctional voiding and elimination may contribute to recurrent febrile UTIs in young children, an association seems to be present in children 5 years old and older.

Child↗
PubMedDate not supplied

Pharmacoepidemiology of urinary tract infections in Iowa Medicaid patients in urban long-term-care facilities.

OBJECTIVE: To describe the therapeutic management of Medicaid patients with urinary tract infections (UTIs) in urban long-term-care facilities (LTCFs) and to link individual therapies to patient outcomes. DESIGN: Retrospective review of medical records in LTCFs of patients who had documented UTIs. METHODS: Patient data were collected from 17 LTCFs in the Des Moines, IA, metropolitan area during a 1-year period starting January 1, 1995. Patients with UTIs were selected from the LTCF infection control logs. Data collected on patients included demographics, concomitant diseases, type of UTI (i.e., symptomatic, asymptomatic, catheter-related), process measures for management, UTI treatment, patient outcomes, and follow-up. Patient outcome data were defined as either cure or no cure. A UTI cure was defined as a negative urine culture while taking antibiotic therapy and/or complete resolution of signs and symptoms, as well as no further treatment given within 2 weeks after the end of treatment. RESULTS: Data were collected on 310 patients who had at least one UTI over the 1-year study period. Patients were primarily elderly (mean age 82.2 +/- 12.3 y), white (95.1%), and female (83.9%). Concomitant diseases were common and about one-fourth (23.0%) of the patients were catheterized. There were 536 UTI events (the unit of analysis) documented over the 1-year period, with about one-half (45.9%) being UTIs with symptoms consistent with uncomplicated lower UTI. Nearly two-thirds (62.3%) of the patients were cured, based on the study definition; there was no association between cure and type of antimicrobial therapy (p = 0.99). Over one-third (35.2%) of the UTIs were treated with a quinolone antibiotic. Others were treated with trimethoprim/sulfamethoxazole (24.4%), nitrofurantoin (13.9%), cephalosporin (10.4%), or ampicillin/amoxicillin (9.8%). Sixty-day follow-up showed no association between type of therapy and hospital readmission, physician follow-up visits, or subsequent UTIs. CONCLUSIONS: There were no differences in cure rates when comparing LTCF UTI patients receiving various regimens. With outcomes being the same, the clinician should closely consider costs of drug therapy in selecting a treatment preference.

Aged↗
PubMed1998

Human neutrophil elastase degrades inter-alpha-trypsin inhibitor to liberate urinary trypsin inhibitor related proteins.

Urinary trypsin inhibitor (UTI) is a physiological protease inhibitor and inter-alpha-trypsin inhibitor (ITI) is regarded as a precursor of UTI. The purpose of this study is to determine the mechanism of the UTI release from ITI. To examine this, ITI was digested by human neutrophil elastase at various concentrations, and UTI-related proteins which were of the same size as UTI were obtained. The amino acid sequence of the 15 amino acid residues at the N-terminal of UTI-related proteins, corresponded to that of UTI. The amino acid sequences of the small amount of peptides detected corresponded to those of peptides from the heavy chain1 (H1) and the heavy chain2 (H2) of ITI, suggesting that most UTI-related proteins do not combine with peptides from the H1 and H2 of ITI. It was also revealed that UTI-related proteins have several physiological activities similar to those of UTI, i.e., human trypsin inhibitory activity, human neutrophil elastase inhibitory activity, inhibition of tumor necrosis factor-alpha (TNF-alpha) production from rat macrophages and of superoxide production from rabbit leukocytes. These results demonstrated that ITI is a precursor of UTI which is digested by human neutrophil elastase to release UTI, and that its elastase inhibitory activity is derived from UTI.

Alpha-Globulins↗
PubMed2006

Urine interleukin-8 as a marker of vesicoureteral reflux in infants.

OBJECTIVE: Vesicoureteral reflux (VUR) is a common finding in children presenting with urinary tract infection (UTI) and prenatally diagnosed urinary tract dilatation and in relatives of index patients. Children with VUR are at risk for ongoing renal damage with subsequent infections. Detecting VUR and renal scarring currently depends on imaging modalities with associated problems of radiation, invasiveness, and expense. Noninvasive methods would greatly facilitate diagnosis and would also help in identifying relatives of index cases who should be screened. Interleukin-8 (IL-8) is produced by epithelial cells of the renal tract in response to inflammatory stimuli and has been shown to increase during acute UTI. The objective of this study was to assess the urine levels of IL-8 as a noninvasive marker of VUR in infants in the absence of a recent UTI episode. METHODS: We evaluated urine concentrations of IL-8 in 59 infants aged 1 month to 2 years. All infants were free of UTI for a minimum of 3 weeks before IL-8 evaluation. Infants were divided into 3 groups: group A, subjects with proven VUR (24 infants aged 0.15-1.95 years, median 0.43); group B, subjects with a history of UTI but negative investigation for VUR (14 infants aged 0.32-1.95 years, median 0.57); and group C, subjects without any history of acute or chronic condition that might impair renal function (21 infants aged 0.08-1.92 years, median 0.33). IL-8 concentrations were determined by a commercially available quantitative enzyme-linked immunosorbent assay. To avoid dilution effects, urinary levels of IL-8 were expressed as the ratio of cytokine-to-urinary creatinine. RESULTS: Results were presented as medians and ranges. The Kruskal-Wallis test, the Mann-Whitney rank sum U test, and the Spearman rank order correlation test were performed for the univariate analysis. Two-tailed P values were calculated and the conventional level of significance P < .05 was applied in all cases. Infants in groups A and B had been free of UTI for a period of 3 to 52 weeks (median, 5.0 weeks) and 3 to 78 weeks (median, 4.5 weeks), respectively, before IL-8 determination. No significant difference was noted in the length of the UTI-free period between groups A and B (P = .469). Urine creatinine concentrations did not differ among groups A, B, and C (medians 1.15, 2.25, and 1.15 micromol/mL, respectively; P = .080). The median urine IL-8/creatinine concentrations (pg/micromol) were 40.5 (range, 2.04-3874) in group A, 1.91 (range, 0.001-386) in group B, and 2.47 (range, 0.002-55.6) in group C. Urine IL-8/creatinine concentrations were significantly higher in group A than both in group B (P = .0003) and in group C (P < .0001). No significant difference was observed between groups B and C (P = .749). In group A, no significant correlation was shown between IL-8/creatinine concentrations and the presence of renal parenchymal damage (P = .506), reflux grade (P = .770), or time from UTI (P = .155). A receiver-operator characteristic curve was constructed by plotting the sensitivity versus the specificity for different cutoff concentrations of IL-8/creatinine. With a cutoff concentration of urinary IL-8/creatinine at 5 pg/micromol, the sensitivity of this marker in diagnosing VUR was 88%, the specificity 69%, the positive prognostic value 66%, and the negative prognostic value 89%. In higher cutoff concentrations, specificity of the marker increased but sensitivity rapidly decreased. CONCLUSIONS: We present evidence that urine IL-8 concentrations remain elevated in infants with VUR even in the absence of UTI and that a cutoff of 5 pg/micromol IL-8/creatinine is of high sensitivity and adequate specificity for diagnosing VUR. Elevated urine IL-8 levels in VUR and renal scarring have already been reported; however, the present study is, to our knowledge, the first to confirm significant differences between infants with VUR and infants with a history of UTI alone and healthy controls, and to suggest a reliable cutoff concentration for diagnosing VUR. Our findings additionally suggest that inflammatory process in VUR is ongoing even after UTI has resolved, pointing against the currently held belief that sterile reflux cannot harm kidneys. The chronic inflammatory cell infiltrate associated with reflux nephropathy rather than VUR itself might offer an explanation for the secretion of IL-8, which may well be independent of reflux grade. Using urine IL-8 for diagnosing VUR is not free of limitations, because IL-8 may be elevated as a result of urinary tract manipulation or undetected UTI. In addition, this study focused on infants and not in older children with longstanding VUR. Increased urine IL-8 concentrations after UTI has resolved is a promising noninvasive marker for an initial screening for VUR in infancy with high sensitivity and adequate specificity.

Biomarkers↗
PubMed2001

Urinary tract infections in children younger than 5 years of age: epidemiology, diagnosis, treatment, outcomes and prevention.

Although the true incidence of urinary tract infections (UTIs) in children is difficult to estimate, they are one of the most common bacterial infections seen by clinicians who care for young children. Except for the first 8 to 12 weeks of life, when infection of the urinary tact may be secondary to a haematogenous source, UTI is believed to arise by the ascending route after entry of bacteria via the urethra. Enterobacteriaceae are the most common organisms isolated from uncomplicated UTI. Infection with Staphylococcus aureus is rare in children without in-dwelling catheters or other sources of infection, and coagulase-negative staphylococci and Candida spp. are associated with infections after instrumentation of the urinary tract. The diagnosis of UTI in young children is important as it is a marker for urinary tract abnormalities and, in the newborn, may be associated with bacteraemia. Early diagnosis is critical to preserve renal function of the growing kidney. A urine specimen for culture is necessary to document a UTI in a young child. Prior to culture, urinalysis may be useful to detect findings supporting a presumptive diagnosis of UTI. The goals of the management of UTI in a young child are: (i) prompt diagnosis of concomitant bacteraemia or meningitis, particularly in the infant; (ii) prevention of progressive renal disease by prompt eradication of the bacterial pathogen, identification of abnormalities of the urinary tract and prevention of recurrent infections; and (iii) resolution of the acute symptoms of the infection. Delay in initiation of the antibacterial therapy is associated with an increased risk of renal scarring. The initial choice of antibacterial therapy is based on the knowledge of the predominant pathogens in the patient's age group, antibacterial sensitivity patterns in the practice area, the clinical status of the patient and the opportunity for close follow-up. Imaging studies to detect congenital or acquired abnormalities are recommended following the first UTI in all children aged <6 years. Patients with significant urinary tract abnormalities and/or frequent symptomatic UTI may benefit from prophylactic antibacterials. The main long term consequence of UTI is renal scarring which may lead to hypertension and end-stage renal disease. Prevention of recurrent UTI focuses on detection, and correction if possible, of urinary tract abnormalities. Interventions that have been associated with a decrease in symptomatic UTI in children with a history of recurrent UTI include relief of constipation and voiding dysfunction.

Anti-Infective Agents, Urinary↗
PubMed2000

Pathogenesis of urinary tract infections: an update.

The pathogenesis of uncomplicated urinary tract infection (UTI) is complex and influenced by many host biological and behavioural factors and by properties of the infecting uropathogens. Most uncomplicated UTIs in women are not associated with underlying functional or anatomical abnormalities of the urinary tract, whereas sexual intercourse, spermicide use, a history of recurrent UTI and recent antimicrobial chemotherapy are important risk factors. A maternal history of UTI and young age at first UTI, as well as sexual intercourse and spermicide use, are risk factors for recurrent UTI in young women. In some young healthy women, especially those with 'low UTI risk' behaviour, features of pelvic anatomy appear to be associated with UTI risk. In postmenopausal women, anatomical and functional characteristics of the genitourinary tract are more strongly associated with UTI risk than in younger women. A genetic predisposition to recurrent UTI is suggested by the association of recurrent UTI in certain age groups with the ABH blood group non-secretor phenotype, a maternal history of UTI and early age at onset of UTI. Virulence determinants of uropathogens are much more important in the normal host than in the host who has a functional or anatomical abnormality of the genitourinary tract.

Journal Article↗