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Biomedical subjects

D T Uehling

Publications and source records attributed to D T Uehling.

At least 37 records · Page 2Linked to original sources

Lipopolysaccharide-responder and nonresponder C3H mouse strains are equally susceptible to an induced Escherichia coli urinary tract infection.

Host defense against bacterial urinary tract infections (UTI) includes both inflammatory and immune responses to infecting bacteria. The cellular events leading up to local inflammation are thought to be under genetic control and initiated by lipopolysaccharides (LPS) of gram-negative bacteria such as Escherichia coli. It has been previously reported that mice which lack functional Lps genes are more susceptible to induced E. coli UTI than mice with normal mitogenic responses to LPS. In contrast to these findings, data in this report demonstrate that LPS-responder and nonresponder C3H mouse strains are equally susceptible to E. coli UTI. When C3H/OuJ (Lps(n)/Lps(n)) and C3H/HeJ (Lps(d)/Lps(d)) were intravesically inoculated with equal numbers of uropathogenic E. coli organisms, neither strain was able to effectively resolve the induced UTI. The inability of C3H/OuJ mice to combat the infection was not due to an impaired response to LPS, nor could defect in the local inflammatory response be identified. The results indicate that factors other than LPS responsiveness are also important in determining hose resistance to UTI.

Animals↗

Living donor nephrectomy: a 20-year experience.

OBJECTIVES: To review the selection criteria and perioperative morbidity in patients undergoing living-related donor nephrectomy. METHODS: Retrospective chart review. RESULTS: Six hundred eighty-one patients underwent living donor nephrectomy during a 20-year period without any mortality. The postoperative morbidity included pneumothorax requiring a chest tube in 7%, urinary tract infection in 5%, wound infection in 4%, and need for blood replacement in 0.3% of patients. Two patients had clinically apparent pulmonary emboli. CONCLUSIONS: Living donor nephrectomy remains a valuable source of kidneys for transplantation but is not without risk. By using care in donor selection and surgical management, operative complications can be kept low.

Adolescent↗

Resolution time of Escherichia coli cystitis is correlated with levels of preinfection antibody to the infecting Escherichia coli strain.

OBJECTIVES: A number of studies in animals have demonstrated that immunization against uropathogenic bacteria can lessen the severity or duration of induced urinary tract infections (UTI). This study examined whether preinfection levels of serum or urinary anti-Escherichia coli antibodies were correlated with length of time needed to resolve an induced E coli cystitis. METHODS: Serum and urine anti-E coli antibody levels in 36 control and 42 vaginally immunized cynomolgus monkeys were measured by enzyme-linked immunosorbent assay. Regression analyses were used to determine correlations between resolution time and preinfection antibody level, and to estimate antibody levels that might be associated with effective resolution of an E coli UTI. RESULTS: Linear regression analysis showed significant correlations between short resolution time and high levels of serum immunoglobulin M (IgM), urinary secretory IgA, and urinary IgG specific for the infecting E coli strain. Serum IgM and urinary IgG anti-E coli levels in monkeys that cleared infections early were significantly higher than in animals with protracted infections. Logistic regression estimated the serum IgM and urinary IgG anti-E coli levels associated with a 50% probability of accelerated clearance to be 3.3 micrograms/mL and 2.7 micrograms/24 hours, respectively. CONCLUSIONS: For this primate model, the observed correlations between short resolution time and pre-existing serum and urinary antibody suggest that antibody-mediated immunity is an important component of host defense against UTI.

Animals↗

Induction of urinary tract infection by intraurethral inoculation with Escherichia coli: refining the murine model.

Murine models are important for studying the induction and pathophysiology of ascending urinary tract infections (UTI). However, when vesicoureteral reflux occurs during intravesical inoculation of mice with bacterial suspensions, it is difficult to distinguish between naturally ascending infections and those resulting from the inoculation procedure. The current study investigated whether introducing a bacterial suspension into the urethra rather than into the bladder could minimize or eliminate this complication. There were no differences in the intensity or time course of bladder infections induced by intraurethral or intravesical inoculation. In contrast, the prevalence of kidney infections was < 7% in mice given 10 microliters of intraurethral inoculations versus nearly 60% in animals inoculated intravesically with 100 microliters. There were equivalent numbers of bacteria in the kidneys after inoculation by either route. Thus, intraurethral inoculation of female mice with a small volume of bacteria appears to simulate most closely the pathophysiology of ascending UTIs in humans.

Animals↗

Western blot analysis of anti-Escherichia coli serum immunoglobulins in women susceptible to recurrent urinary tract infections.

The basis for increased susceptibility of some women to recurrent urinary tract infections (UTIs) is not clear; increased susceptibility may be due to host factors that promote increased colonization of the vaginal and bladder mucosa with uropathogens or to decreased immune responses to uropathogens. Anti-Escherichia coli antibody specificities in sera from UTI patients and controls were comprehensively assessed to determine whether UTI-susceptible and -nonsusceptible women differed in their capacities to make antibodies to individual E. coli antigens. Sera were analyzed by one-dimensional Western blots using antigens prepared from uropathogenic E. coli. The results showed that sera from subjects without a history of recurrent UTIs contained IgG antibodies to specific E. coli antigens more often than did sera from UTI-susceptible patients. These data suggest that hyporesponsiveness to specific E. coli antigens may be linked to increased UTI susceptibility in some women.

Adult↗

Living related and unrelated donors for kidney transplantation. A 28-year experience.

OBJECTIVE: The objective of this study was to analyze a single center's 28-year experience with 1000 living donor transplants. SUMMARY BACKGROUND DATA: The number of potential renal transplant recipients far exceeds the number of cadaveric donors. For this reason, living related donors (LRDs) and, more recently, living unrelated donors (LURDs) have been used to decrease the cadaveric donor shortage. METHODS: From November 15, 1966, until August 5, 1994, 1000 living donor transplants were performed; 906 were living related and 94 were living unrelated transplants. Results were divided into precyclosporine (1966-1986, era I) and cyclosporine (1986-1994, era II) eras. Patient and graft survivals were compared between diabetic and nondiabetic recipients, between LRDs and LURDs, and according to human leukocyte antigen (HLA) matching. Donor mortality, morbidity, and postoperative renal function were also analyzed. RESULTS: The 5-, 10-, and 20-year graft survivals were 78.8%, 64.8%, and 43.4%, respectively. Patient and graft survival improved in era II (patient = 87.0% vs. 81.7%, p = 0.03; graft = 72.9% vs. 67.7%, p = 0.04). Nondiabetic patient and graft survivals were better than diabetic patient survivals in both eras. However, diabetic patient survival improved in era II (78.0% vs. 66.9%, p = 0.04). In era II, HLA-identical recipients had better graft survival than haploidentical or mismatched recipients (91.7% vs. 67.3% and 66.1%, p = 0.01). No difference between haploidentical LRDs and LURDs was seen. One donor death occurred in 1970, and 17% of donors developed postoperative complications. CONCLUSION: Living related and unrelated renal donation continues to be an important source of kidneys for patients with end-stage renal disease.

Adult↗

Phase I clinical trial of vaginal mucosal immunization for recurrent urinary tract infection.

In a phase I clinical trial to test safety and patient acceptance 25 women with a history of recurrent urinary tract infections but no identifiable anatomic abnormality received a multivalent vaccine instilled into the vagina. The vaccine contained 6 heat-killed Escherichia coli strains and 4 nonE. coli uropathogens. Only minimal adverse reactions were observed in the 5-month period following immunization. Total vaginal and urinary IgG and IgA increased significantly (p < 0.01 by repeated measures analysis of variance). Serum antibodies to some of the nonE. coli strains but not to the E. coli strains increased after vaginal immunization. While efficacy is yet to be shown, this study indicates that this vaginally applied urinary tract infection vaccine is well tolerated, and capable of increasing vaginal and urinary antibody.

Adjuvants, Immunologic↗

Residual retroperitoneal mass following chemotherapy for infantile yolk sac tumor.

A child treated with chemotherapy for disseminated yolk sac tumor had a residual retroperitoneal mass after normalization of serum alpha-fetoprotein. The mass was excised and histologically showed only fibrous tissue, necrosis and calcification. To our knowledge this is the first case reported of a prepubertal yolk sac tumor associated with a residual retroperitoneal mass.

Antineoplastic Combined Chemotherapy Protocols↗

Vaginal immunization of monkeys against urinary tract infection with a multi-strain vaccine.

Cynomolgus monkeys were treated with a vaccine containing 10 heat-killed uropathogenic bacteria including 6 Escherichia coli strains. The multi-strain vaccine was administered either as a vaginal surface immunogen or intramuscularly. Following an induced E. coli cystitis, bladder infections were significantly reduced compared with controls at 1 and 2 weeks (intramuscular route) or 1 week (vaginal route) after UTI. This vaccine has been shown to be efficacious against cystitis in humans when given parenterally and has now proved efficacious in nonhuman primates by the vaginal mucosal route.

Animals↗

Hinman syndrome: a vicious cycle.

In Hinman syndrome, psychosocial problems are associated with voiding dysfunction, urinary tract infections, and incontinence. The latter can exacerbate the former and a vicious cycle can result in worsening symptoms and renal sequelae. Although interruption of this cycle is difficult, urologic recognition and treatment can have a positive effect. Five cases are presented that demonstrate the cyclical features of Hinman syndrome.

Affective Symptoms↗

Congenital immunodeficiencies in mice increase susceptibility to urinary tract infection.

Severe combined immunodeficient (SCID), T cell deficient, and immunocompetent mice were challenged intravesically with viable uropathogenic Escherichia coli. In comparison to immunocompetent controls, SCID mice had significantly greater numbers of viable E. coli in their bladders and kidneys 7 days after inoculation. Splenic anti-E. coli antibody-forming cells (AFC) were virtually absent in SCID mice at 7.0 days after infection. Adoptive transfer of spleen cells from E. coli-immunized immunocompetent mice to SCID mice enhanced their resistance to urinary tract infection (UTI), as evidenced by lower bacterial counts in bladder and kidneys following an induced infection. Congenitally T cell deficient nude mice and immunocompetent heterozygous controls had equivalent bladder and kidney infection levels at 2 and 7 days after UTI. Immunocompetency thus appears to play a significant role in resistance to E. coli UTI in this animal model. Since mice deficient only in T cells did not show increased UTI susceptibility, T cell-independent antibody responses may be an important immunologic defense mechanism.

Animals↗

Abdominoscrotal hydrocele: diagnosis by herniogram and ultrasound.

A four-month-old male infant presented with a lower abdominal mass and bilateral hydroceles. With pressing on the abdominal mass, the right hydrocele became larger. Herniogram and ultrasound led to the diagnosis of abdominoscrotal hydrocele which was successfully repaired through an extraperitoneal and intraperitoneal approach.

Abdomen↗

Bilateral epidermoid cysts of the testicle.

An 11-year-old boy presented with bilateral testicular masses that consisted of hyperechoic centers with hypoechoic rims on ultrasound. Surgical exploration revealed bilateral epidermoid cysts. To our knowledge this is the first reported case of bilateral epidermoid cysts in a child. Recognition of this entity requires surgical confirmation but it may obviate removal of the testicle.

Child↗

Vesicoureteric reflux in sibships.

A family with 4 of 6 siblings manifesting vesicoureteric reflux is presented. Reflux could not be demonstrated in preceding and succeeding generations in this family. Genetic analysis suggests that most instances of familial vesicoureteric reflux arise secondary to expression of autosomal dominant single genes with incomplete penetrance. Screening of sibships for reflux might be most appropriately carried out by urine analysis, culture and ultrasound imaging.

Child↗

Immunization against urinary tract infection with a multi-valent vaginal vaccine.

Systemic and local immune responses are thought to play an important role in susceptibility to urinary tract infection. In an attempt to boost local immunity, a vaccine was administered parenterally or vaginally to two mouse strains. Both routes of immunization increased the number of splenic antibody-forming cells against the bacterial strains in the vaccine. Following vaginal or parenteral immunization and subsequent induction of cystitis with live E. coli, immunized animals had fewer viable bladder E. coli than non-immunized animals.

Animals↗

Decreased immunologic responsiveness following intensified vaginal immunization against urinary tract infection.

In an attempt to further increase the protective effect of vaginal immunization against urinary tract infections in Cynomolgus monkeys, the immunogen of killed E. coli was given more times, in larger amounts, and with the adjuvant MDP. Instead of increasing the protective effect, no protective effect on induced cystitis was observed. In addition, rises in urinary and serum immunoglobulins previously observed after vaginal immunization and induced cystitis were lessened. These observations appear to correspond with the classical concepts of immunologic unresponsiveness.

Acetylmuramyl-Alanyl-Isoglutamine↗

Adherence of uropathogenic E. coli to differentiated human uroepithelial cells grown in vitro.

A quantitative in vitro model to measure E. coli adherence to differentiated human uroepithelial cells has been developed. Primary cultures of uroepithelial cells were initiated from normal ureteral epithelium. Adherence of uropathogenic 3H-labelled Escherichia coli to postconfluent human uroepithelial cells was directly related to the bacteria:epithelial cell ratio during incubation. Bacterial attachment was inhibited either by mannose or by urine containing anti-E. coli antibodies. Transmission electron microscopy showed that epithelial cells differentiated in vitro to resemble normal uroepithelium in vivo. Furthermore, electron microscopy showed specific adherence of bacteria to the glycocalyx of microvilli of the superficial uroepithelial cells in vitro in a manner which closely mimics the in vivo interaction. This model of bacterial adherence permits in vitro analysis of adhesin-receptor interactions between uropathogenic E. coli and a layer of viable uroepithelial cells similar to those lining the bladder.

Animals↗

Initiation of vesicoureteral reflux after heminephrectomy for ureterocele.

In a male infant profuse flank urine drainage developed after heminephrectomy for ureterocele. Cystograms then showed bilateral vesicoureteral reflux where none had been present preoperatively. The flank drainage resolved promptly after catheter drainage of the bladder. Decompression of a ureterocele may cause initiation of vesicoureteral reflex.

Drainage↗