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PubMed1997

Cytokine antagonists in aged subjects and their relation with cellular immunity.

Host responses to infectious and inflammatory stimuli are altered with aging. Because cytokines and their antagonists are significant factors in these host responses, the present research on aged subjects was designed to investigate plasma concentrations of the cytokines interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) and those of their antagonists IL-1 receptor antagonist (IL-1ra) and soluble TNF receptor (sTNFr). For this research, 122 apparently healthy aged subjects (79.6 +/- 5.8 yr), 39 aged individuals with documented urinary tract infections (UTIs) (81.6 +/- 6.3 yr), and 100 young controls (39.32 +/- 11.2 yr) were included. Plasma IL-1 beta, TNF alpha, IL-1ra, sTNFr (55 kDa), and neopterin were measured using enzyme-linked immunosorbent assay techniques. In subsets of normal aged subjects and UTI patients, we investigated relations between plasma concentrations of cytokine antagonists and IL-2 production by phytohemagglutinin-stimulated peripheral blood mononuclear cells. The results show that plasma concentrations of both IL-1ra and sTNFr were greater in healthy aged subjects than in young controls. Plasma neopterin, a product of activated monocytes/macrophages, was likewise elevated in the aged. IL-1 and TNF were not detectable in the majority of plasma samples. There was a positive correlation between neopterin concentration and both IL-1ra and sTNFr. There was a significant negative correlation between plasma IL-1ra and IL-2 production by phytohemagglutinin-stimulated peripheral blood mononuclear cell in healthy aged subjects. IL-1ra and sTNFr concentrations were significantly greater in patients with UTI than in the healthy aged subjects. In UTI patients IL-2 production in vitro was lower than in healthy subjects, but there was no significant correlation with IL-1ra in plasma. Therefore, plasma concentrations of cytokine antagonists are increased in plasma of apparently healthy aged subjects. Elevated concentrations of neopterin suggest that this increase can be traced to monocyte activation. The negative correlation between plasma IL-1ra and IL-2 production in vitro suggests that enhancement of this cytokine antagonist can contribute to immunodepression of aging. We propose that unapparent infections in aged subjects cause monocyte activation and release of cytokine antagonists. These cytokine antagonists reduce IL-2 production and the capability of T cells to proliferate, thereby inhibiting responses in the elderly.

Adult↗
PubMed1998

The mouse Y chromosome interval necessary for spermatogonial proliferation is gene dense with syntenic homology to the human AZFa region.

The Delta Sxrb deletion interval of the mouse Y chromosome contains Spy, a spermatogenesis factor gene(s) whose expression is essential for the postnatal development of the mitotic germ cells, spermatogonia. The boundaries of Delta Sxrb are defined by the duplicated genes Zfy1 and Zfy2 and four further genes have previously been mapped within the interval: Ube1y and Smcy, linked with Zfy1 on a contig of 250 kb, and Dffry and Uty, which were unanchored. The interval was estimated to be >450 kb. In order to identify any further gene(s) that may underlie Spy, systematic exon trapping was performed on an extended contig, anchored on Zfy1, which covers 750 kb of the Delta Sxrb interval. Exons from two novel genes were isolated and placed together with Dffry and Uty on the contig in the order Dffry-Dby-Uty-Tspy-Eif2gammay-Smcy- Ube1y-Zfy1. All the genes, with the double exception of Tspy, are X-Y homologous and produce putatively functional, spliced transcripts. The tight linkage and order of Dffry, Dby and Uty was shown to be conserved in deletion intervals 5C/5D of the human Y chromosome by the construction of a contig of human PAC and YAC clones; this represents the first example of syntenic homology between Y chromosomes from two distinct mammalian orders. Interval 5C/5D contains the distal boundary of the AZFa interval, which, like Delta Sxrb, is believed to be necessary for spermatogonial development in the prepubertal testis. Our results therefore show that AZFa and Spy may be encoded by homologous genes.

Animals↗
PubMed1998

The UTX gene escapes X inactivation in mice and humans.

We recently have identified a ubiquitously transcribed mouse Y chromosome gene, Uty , which encodes a tetratricopeptide repeat (TPR) protein. A peptide derived from the UTY protein confers H-Y antigenicity on male cells. Here we report the characterization of a widely transcribed X-linked homologue of Uty , called Utx , which maps to the proximal region of the mouse X chromosome and which detects a human X-linked homologue at Xp11.2. Given that Uty is ubiquitously transcribed, we assayed for Utx expression from the inactive X chromosome (Xi) in mice and found that Utx escapes X chromosome inactivation. Only Smcx and the pseudoautosomal Sts gene on the mouse X chromosome have been reported previously to escape inactivation. The human UTX gene was also found to be expressed from Xi. We discuss the significance of these data for our understanding of dosage compensation of X-Y homologous genes in humans and mice.

Amino Acid Sequence↗
PubMed1980

Urinary tract infection caused by Staphylococcus saprophyticus.

This study was designed to determine whether Staphylococcus saprophyticus was an important cause of urinary tract infection (UTI), as has been reported by European, but not by American, investigators, S. saprophyticus was the second most common cause of UTI in young (mean age, 20 years), sexually active female outpatients without known preexisting kidney disease or preceding manipulation of the urinary tract. Most cases presented as acute cystitis, but frank pyelonephritis and UTI in pregnant females were observed. The organism was rarely found as a contaminant in urine cultures. When present in the mucocutaneous flora of the anal-urogenital area, the organism was significantly associated with UTI by the same organism. These results show that S. saprophyticus should be accepted as an important urinary tract pathogen of young female patients in the United States. A simple adequate laboratory identification may be based on resistance to novobiocin (disk diffusion test), absence of hemolysis and coagulase, and intense pigment production (65% of strains yellow, 35% white).

Adolescent↗
PubMed1981

Antibodies to lipid A during urinary tract infection.

Serum levels of antibodies to lipid A were determined with an enzyme-linked immunosorbent assay in 26 girls with their first known symptomatic urinary tract infection (UTI) and in 15 girls with asymptomatic bacteriuria (ABU). Also included were six female patients with recurrence of acute upper UTI, five of whom had renal changes after the infections; 28 female patients with renal scarring but not symptomatic UTI at the time of investigation; and uninfected individuals. IgG and IgM antibodies to lipid A were found in approximately 50% of the uninfected children older than two years of age. Girls with acute cystitis, acute pyelonephritis, or ABU showed significantly elevated levels of IgG antibodies to lipid A as compared with children with no history of UTI. High levels of IgG antibodies to lipid A may be indicative of severe renal infection and development or progression of renal parenchymal reduction. The diagnostic value of determining levels of antibodies to lipid A is discussed.

Adolescent↗
PubMed2002

HY peptides modulate transplantation responses to skin allografts.

Injection of female C57BL/6 mice with immature female bone marrow-derived dendritic cells (BMDC) pulsed with a single immunodominant HY(Db) Uty peptide, WMHHNMDLI, induces prolonged survival of syngeneic male skin grafts. In contrast, injection of immature female BMDC pulsed with a single MHC class I-restricted HY(Ab) Dby peptide, NAGFNSNRANSSRSS, causes immunization similar to that following injection of male cells. Tolerance induced by HY(Db) Uty peptide pretreatment is not characterized by clonal deletion: long-term tolerant mice maintain circulating HY(Db) Uty tetramer(+) T cells which expand following exposure to male cells in vivo or in vitro. Tolerance to male skin grafts can be adoptively transferred into neonatal females with splenocytes from tolerant donors. Tolerance is specific-third-party skin grafts are rejected. We propose that tolerance in this model is initiated by cognate interaction of HY(Db) Uty-specific CD8(+) T cells with their ligand, presented either on the injected immature BMDC or on recipient DC. This interaction leads to incomplete activation of the CD8(+) T cells resulting in diminished responsiveness of CD4(+) and CD8(+) T cells specific for HY peptide epitopes subsequently presented on the male graft.

Animals↗
PubMed1988

Single low-dose ofloxacin for the treatment of uncomplicated urinary tract infection in young women.

Fifty premenopausal women with uncomplicated urinary tract infection (UTI) were treated with a single dose of 100 mg of ofloxacin. Duration of symptoms before the treatment, number of episodes of UTI during the last year, association with sexual activity, and the use of contraceptives were evaluated in relation to the clinical and microbiological response. Forty-seven women (94%) were cured clinically and microbiologically three days after treatment. Follow up at 28 days disclosed that 43 (86%) were free of symptoms and in 40 (80%) the urinary cultures were negative. Significantly higher rates of microbiological failure or reinfection were found among women with three or more episodes of UTI during the last year. This study shows that a single dose of ofloxacin is effective for therapy of uncomplicated UTI in young women.

Adolescent↗
PubMed1994

Evaluation of antibiotics for treatment of urinary tract infections.

The evaluation of new regimens for treatment of urinary tract infections (UTIs) has often been unsatisfactory. A major reason has been the lack of internationally accepted guidelines for design and conduct of UTI trials. The introduction of new guidelines has largely overcome this problem. However, some problems remain, and this review especially addresses the problem of defining outcomes of treatment of UTI. New, somewhat controversial definitions of bacteriuria are well documented for various types of UTI, but have not been properly evaluated as end-points for defining bacteriological responses to treatment.

Anti-Bacterial Agents↗
PubMed1994

Urinary tract infection in early childhood.

The infantile kidney is most vulnerable to damage from vesicoureteric reflux combined with urinary tract infection. A UTI, as well as giving rise to significant morbidity, may provide the clue to an underlying congenital abnormality such as obstructive uropathy. Urinary tract infection is less prevalent in circumcised boys and infants who are breastfed. Often the diagnosis of UTI is not thought of because of the non-specific nature of the symptoms in this age group and the difficulties of obtaining and interpreting urine cultures. Too little use and attention is paid to proper collecting bags and clean catch specimens. Suprapubic aspiration should always be considered in the septicaemic infant where UTI is high on the list of differential diagnoses. Escherichia coli is responsible for most UTIs although in very young infants, kidneys may be involved secondary to septicaemic infection. Antibiotic therapy should be prompt and investigations comprehensive in young infants. Most children with vesicoureteric reflux are managed conservatively with long term prophylactic antibiotics.

Anti-Bacterial Agents↗
PubMed1995

An audit of ciprofloxacin use in a district general hospital.

An audit of ciprofloxacin use at Southmead Hospital, Bristol was carried out for forty patients treated in early 1992 employing a modified Delphi technique with six assessors. Most patients assessed (20/40, 50%) had urinary tract infections (UTIs), 5/40 (12.5%) had chest infections, 4/40 (10%) had bacterial gastroenteritis and 3/40 (7.5%) had either bacteraemia or infection following an orthopaedic procedure. A likely bacterial pathogen was isolated from 32/40 (80%) of patients; 14/32 (44%) had Pseudomonas aeruginosa infections and from the remainder Enterobacteriaceae including Salmonella spp. (non-typhoid) were cultured. Oral therapy with ciprofloxacin was used in 37 (93%) of the 40 patients, and the three others received iv treatment. In 21/35 (60%) of patients where an assessment was made by majority scoring, a quinolone was felt to be clinically justified. A quinolone was least likely to be thought justified if the patient had a chest infection. The assessors had few concerns about the effectiveness or toxicity of ciprofloxacin but for 41% (14/34) of patients, where there was a majority opinion, a cheaper alternative was felt to be available; most of these patients had hospital-acquired UTIs caused by Enterobacteriaceae. The duration of therapy was felt to be too long in 35% (10/29) of patients, mainly because of prolonged treatment of UTIs. In some cases of P. aeruginosa infection the assessors would have used higher doses than those prescribed. Ciprofloxacin was the quinolone of choice in 24/32 (75%) of assessable cases. Norfloxacin was chosen to treat UTI due to multi-resistant Enterobacteriaceae in 6.2% (2/32) cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Infective Agents↗
PubMed2000

Increasing resistance to fluoroquinolones in escherichia coli from urinary tract infections in the netherlands.

In continuous surveillance of routine samples from five Dutch laboratories, we studied resistance to the antibiotics most commonly prescribed for urinary tract infections (UTI) in The Netherlands, namely norfloxacin, amoxycillin, trimethoprim and nitrofurantoin, from 1989 to 1998 in >90000 Escherichia coli isolates. Resistance to norfloxacin increased from 1.3% in 1989 to 5.8% in 1998. Multiresistance, defined as resistance to norfloxacin and at least two of the other three antibiotics, increased from 0.5% in 1989 to 4. 0% in 1998. Multivariate analysis of the norfloxacin resistance demonstrated that this yearly increase (the odds ratio was 1.0 in 1989, 1.6 in 1992, 2.9 in 1995 and 6.1 in 1998) was independent of other determinants of resistance to norfloxacin, such as age, gender and origin of the isolate. Analysis of strata, classified by year, age and gender, demonstrated an association between prescription of fluoroquinolones (defined daily doses per case of UTI) and resistance to norfloxacin in E. coli (P < 0.001). There was no significant association with the prescription of nitrofuran derivatives (nitrofurantoin) and trimethoprim with or without sulphamethoxazole. The yearly increase of resistance to fluoroquinolones in E. coli from UTI may stem from increased prescription of fluoroquinolones for UTI. Resistance of E. coli to these agents is likely to increase further as fluoroquinolone use increases in future.

Adolescent↗
PubMed2003

Prior antimicrobial drug exposure: a risk factor for trimethoprim-sulfamethoxazole-resistant urinary tract infections.

OBJECTIVES: Antimicrobial drug use is believed to be an important risk factor for the emerging problem of antimicrobial drug resistance, yet strong evidence for the causal relationship in community settings has been limited. Detailed analysis of this risk factor at the level of the individual patient has been hampered by limited availability of drug exposure data among patients with outpatient infections. We used a novel data system to identify patterns of individual antimicrobial drug exposures associated with trimethoprim-sulfamethoxazole-resistant urinary tract infections (UTIs). MATERIALS AND METHODS: This was a retrospective case-control study. Subjects were veterans with Gram-negative UTIs seen at the Philadelphia VA Medical Center from 1 July 1996 to 31 December 1999. Subjects were linked to a national VA outpatient pharmacy database. Cases and controls were identified based on the results of trimethoprim-sulfamethoxazole susceptibility testing. RESULTS: Three hundred and ninety-three veterans with UTIs could be linked to electronic pharmacy records. The overall rate of trimethoprim-sulfamethoxazole drug resistance was 13%, without significant annual variation. Antimicrobial drug exposure within 6 months was strongly associated with the probability of a trimethoprim-sulfamethoxazole-resistant infection (OR = 4.1, 95% CI 2.2-7.5). This association extended to exposure to other antimicrobial drugs in addition to trimethoprim-sulfamethoxazole and the overall association displayed a dose-response relationship in terms of the number of prior drug exposures. CONCLUSIONS: Prior antimicrobial drug exposure is a strong risk factor for infection with trimethoprim-sulfamethoxazole-resistant Gram-negative bacteria among patients with UTIs.

Adolescent↗
PubMed2006

Clinical relevance of laboratory-reported antibiotic resistance in acute uncomplicated urinary tract infection in primary care.

OBJECTIVES: To determine whether patients with an uncomplicated community-acquired urinary tract infection (UTI) and an isolate resistant to trimethoprim had worse clinical outcomes following empirical treatment with trimethoprim 200 mg twice daily for 3 days than did those with a susceptible isolate. PATIENTS AND METHODS: This was a prospective cohort study of clinical outcome. We enrolled 497 women (>or=18-70 years) presenting to general practitioner surgeries in Norwich and Gloucester with at least two symptoms of acute (<7 days) uncomplicated UTI. Significant bacteriuria was defined as >or=10(4) cfu/mL from a mid-stream urine (MSU). RESULTS: Of enrolled patients 75% (334/448) had significant bacteriuria, and trimethoprim resistance was present in 13.9% (44/317) of isolates. Patients with resistant isolates had a longer median time to symptom resolution (7 versus 4 days, P=0.0002), greater reconsultation to the practice (39% versus 6% in first week, P<0.0001), more subsequent antibiotics (36% versus 4% in first week, P<0.0001) and higher rates of significant bacteriuria at 1 month (42% versus 20% with susceptible isolate, P=0.04). Half of patients reconsulting in the first week had a resistant organism. CONCLUSIONS: Patients with uncomplicated UTI caused by trimethoprim-resistant organisms had significantly worse clinical outcomes than those with trimethoprim-susceptible organisms. Nevertheless, trimethoprim resistance was rarer than predicted from routine laboratory submissions and we calculate that 23 women require microbiological investigation to prevent one reconsultation arising from resistance-based treatment failure. We therefore suggest empirical antibiotic treatment in acute, uncomplicated UTIs. If patients reconsult in the first week, we suggest a change of antibiotic treatment with urine culture and susceptibility testing then done. More generally, laboratory resources should concentrate on resistance surveillance to inform empirical antibiotic choice.

Acute Disease↗
PubMed1988

Urinary lactic acid dehydrogenase activity and the site of urinary tract infections.

A report that elevated urinary lactic acid dehydrogenase (LDH) isoenzyme 5 activity is a reliable tool for separating patients with upper from those with lower urinary tract infections (UTIs) led us to study urinary LDH enzyme activity in girls having bladder washout studies to localize the site of infection. Urinary LDH isoenzyme 5 activity in 64 instances of lower UTI was 16.1 +/- 3.3%, a value not significantly different than that of 18.2 +/- 12.6% found in 26 instances of upper tract infection (t = 0.8726, P = 0.1928). The data show that LDH isoenzyme 5 activity is of no value for localization of the site of a UTI. The data of these studies also showed that urinary LDH enzyme activity clearly separates girls with UTIs from those without infections, but it is unlikely that this finding will be of value in diagnosis or management.

Adolescent↗
PubMed2001

Empiric use of cefepime in the treatment of serious urinary tract infections in children.

BACKGROUND: Urinary tract infections (UTIs) are common in childhood. They represent a significant proportion (10%) of hospital-acquired infections in children. Bacteria causing UTIs in children vary, depending on the setting (community-acquired vs. nosocomial), underlying anatomic anomalies and concurrent medical conditions. OBJECTIVE: To review published and unpublished clinical studies that have used cefepime for the treatment of UTIs in children. METHODS AND RESULTS: In two recent multicenter, randomized trials, cefepime (50 mg/kg/dose every 8 h and every 12 h) was compared with ceftazidime (50 mg/kg/dose every 8 h) for the treatment of serious urinary tract infections including pyelonephritis in children less than 12 years of age. In these studies a favorable clinical and microbiologic response was observed in >95% of cefepime-treated and ceftazidime-treated children assessed at the end of treatment. CONCLUSIONS: These results indicate that cefepime represents an important therapeutic option for the treatment of serious UTIs in children.

Adolescent↗
PubMed2001

Usefulness of procalcitonin and C-reactive protein rapid tests for the management of children with urinary tract infection.

BACKGROUND: Urinary tract infection (UTI) is a common problem in children. Because clinical findings and commonly used blood indices are nonspecific, the distinction between lower and upper urinary tract infection cannot be made easily in this population. However, this distinction is important because renal infection can induce parenchymal scarring. The objective of this study was to determine the accuracy of procalcitonin (PCT) compared with C-reactive protein (CRP) rapid tests to predict renal involvement in children with febrile UTI. METHODS: PCT and CRP were measured in the blood of children admitted to the emergency room with fever, signs and symptoms of urinary tract infection and/or a positive urine dipstick analysis. Renal parenchymal involvement was assessed by a 99mTc-labeled dimercaptosuccinic acid renal scan in the acute phase of infection in all children. Sensitivity, specificity and likelihood ratios were determined for both tests. RESULTS: Fifty-four children with a proven urinary tract infection were enrolled: 63% had renal involvement; and 37% had infection restricted to the lower urinary tract. No difference was found for age, sex and total white blood cell count between the groups. The calculated likelihood ratios of procalcitonin and C-reactive protein rapid tests were between 3.8 and 7 and 1.5 and 2.8, respectively. A positive PCT value predicted renal involvement in 87 to 92% of children with febrile UTI, compared with 44 to 83% using CRP values. CONCLUSIONS: A rapid determination of procalcitonin concentration could be useful for the management of children with febrile UTI in the emergency room.

Adolescent↗
PubMed1995

Adequacy of follow-up in children diagnosed with urinary tract infections in a pediatric emergency department.

A retrospective chart review was undertaken to determine primary care provider (PCP) notification of patient visits and appropriateness of follow-up in children discharged from an inner city, university-affiliated children's emergency department with the diagnosis of urinary tract infection (UTI). Seventy-five charts met criteria for review, and phone calls were made to the PCP/families to obtain follow-up information. Statistical analysis was performed using the chi2 analysis and Fisher's exact test. The PCP was notified of the patient's diagnosis at the time of the ED visit in 24 cases (32%) and was aware of the ED visit/diagnosis of UTI in a total of 53 (71%). Children were more likely to have a repeat urine culture in follow-up if the PCP was aware of the diagnosis (60%) than if the PCP was not aware (9%) chi2 = 14.496 P < 0.001. Forty-seven children met criteria commonly accepted for radiographic evaluation. Nineteen children, whose PCPs were aware of their diagnosis, met criteria and had studies performed. Children were more likely to receive appropriate radiographic evaluation if their PCPs were aware of their diagnoses of UTI 19/35 (54%) than if their PCPs were unaware of their diagnoses 0/12 (0%). Fisher's exact two-tailed t test P < 0.001. We conclude that failure of PCP notification can impact negatively on appropriate patient follow-up and that, in many cases, PCPs are not following current recommendations in the management of children with UTIs.

Adolescent↗
PubMed2002

Test characteristics of the urine Gram stain in infants <or= 60 days of age with fever.

OBJECTIVE: The utility of the Gram stain for the preliminary diagnosis of urinary tract infections (UTI) in infants or= 38.0 degrees C presenting to a pediatric emergency department during 2 consecutive winter seasons. Single pathogen growth of >or= 10(4) cfu/mL from a catheterized specimen and >or= 10(3) cfu/mL from a suprapubic specimen was considered positive. A positive Gram stain was defined as the identification of any organisms. Urinalysis was tested for the presence of nitrites and for leukocyte esterase (LE). Urine microscopy was analyzed for white blood cells per high power field (WBC/hpf). RESULTS: Fourteen of 246 patients were excluded; 11 because no Gram stain was completed. Of the remaining 232 patients, Gram stain had a sensitivity of 85.2% (95% CI 71.9-98.6%), a specificity of 99.0% (95% CI 97.7-100%), a likelihood ratio for a positive test of 87.3 (95% CI 21.8-349.9), and a likelihood ratio for a negative test of 0.15 (95% CI 0.06-0.37). There were 193 specimens for which a Gram stain and a complete UA and microscopy were completed and compared. Urine microscopy had a lower sensitivity and specificity than Gram stain for both >or= 5 WBC/hpf and >or= 10 WBC/hpf. In addition to the Gram stain, a dipstick negative for nitrites and LE had a low negative likelihood ratio (0.16), useful for decreasing the likelihood of a UTI. CONCLUSIONS: The Gram stain has excellent test characteristics for the preliminary diagnosis of a UTI in febrile infants. Patient disposition and therapy will likely change if clinical protocols and guidelines use the Gram stain rather than urine microscopy for preliminary diagnosis of UTI in infants.

Female↗