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Biomedical subjects

D T Uehling

Publications and source records attributed to D T Uehling.

At least 19 recordsLinked to original sources
PubMed2000

Urinary tract abnormalities in children with acute focal bacterial nephritis.

OBJECTIVE: To review the presentation, methods of diagnosis, and incidence of concomitant urological abnormalities in children with acute focal bacterial nephritis (AFBN, also known as lobar nephronia, a severe nonliquefactive infection involving one or more renal lobules). PATIENTS AND METHODS: Sixteen children (age range 6 months to 9 years) diagnosed with AFBN over a 5-year period were retrospectively reviewed. Their age, gender, presenting symptoms, presence of urinary tract abnormalities, radiological imaging and treatment were assessed. RESULTS: All 16 children received intensive intravenous and oral antibiotics. Ten required intervention for predisposing conditions including vesico-ureteric reflux (four), bladder diverticulum (one), renal and peri-rectal abscess (two), ureteric or bladder calculi (two), and renal mass (one). In addition, three children had reflux not requiring surgery; one had multiple renal calyceal diverticula, one had Hinman syndrome and one had leukaemia. CONCLUSION: Acute focal bacterial nephritis is being diagnosed with increasing frequency through increasing awareness and advances in imaging modalities. Active urological evaluation is warranted because of the high incidence of urinary tract abnormalities. In addition to antibiotics, intervention was needed in most children in this series.

Acute Disease↗
PubMed1999

The urinary tract response to entry of pathogens.

The urinary tract response to the entry of pathogens is complex and involves multiple aspects of the immune system. Herein we have divided them into cytokine, immunoglobulin, and cellular responses. Our current understanding suggests that interleukin 6 (IL-6) and IL-8 are the major contributors to the cytokine response. Both IL-6 and IL-8 are produced locally and systemically as part of the initiation of an inflammatory reaction. The cellular response becomes clinically apparent by the appearance of polymorphonuclear neutrophils (PMNs) in the urine. The contribution of gamma delta T-lymphocytes is beginning to be appreciated due to the use of gene-knockout mice in studies of urinary tract infection (UTI). B-lymphocytes are important because antibody response to UTI is important. In addition to the classic systemic antibody response, a local antibody response dominated by secretory immunoglobulin A (sIgA) has been shown to play a major role in the host response to UTI. Efforts to create a vaccine against UTI have focused on stimulation and intensification of this local sIgA production. Investigation continues to define the role of these responses, explain how they interact, and elucidate other aspects of the immune response to UTI that are yet unknown. Ultimately, this work aims to provide more effective treatment and prevention of UTI in those susceptible to invasions of the urinary tract by pathogens. Comprehension of how these responses interact may lead to a better understanding of UTI susceptibility and promote new and innovative types of treatment.

Animals↗
PubMed1999

Müllerian-type epithelial tumor arising within a torsed appendix testis.

Because it is a remnant of the müllerian duct system, the appendix testis contains müllerian epithelium that theoretically may produce epithelial tumors similar to those that occur in the female genital tract. Few reports of tumors of müllerian origin arising in the testis exist, and rarely are neoplasms arising from the appendix testis identified. We present a case of a serous cystic neoplasm of low malignant potential derived from müllerian-type epithelium that was located in the torsed appendix testis of a young, otherwise healthy, boy.

Adolescent↗
PubMed1999

Association of human leucocyte antigen phenotype with vaccine efficacy in patients receiving vaginal mucosal immunization for recurrent urinary tract infection.

Immune responses to specific antigens can be influenced by an individual's genetic make-up. We examined whether the efficacy of a vaginal mucosal vaccine for urinary tract infections (UTI) was affected by a patient's human leucocyte antigen (HLA) phenotype. Urinary tract infection data and the HLA phenotypes of 47 women participating in a phase II clinical trial of immunization for recurrent UTI were statistically analysed for associations between HLA-A, -B, -DR, or -DQ phenotype and postimmunization infection course. Women who received the vaccine and had HLA-DR phenotypes other than DR2 had significantly delayed times to re-infection compared with women receiving placebo. Vaccine-treated patients with the HLA-DR2 phenotype had re-infection courses that were not different than women receiving placebo. These results indicate that the efficacy of a vaginal mucosal UTI vaccine may be influenced by an individual's HLA-DR phenotype.

Bacterial Infections↗
PubMed1999

Susceptibility of immunodeficient gene-knockout mice to urinary tract infection.

PURPOSE: Clinical and experimental evidence indicates that mucosal immunity to urinary tract infection involves B and T-cell functions. The present study was conducted to assess the susceptibility of immunocompetent and immunodeficient mice with genetically engineered deletions in T and B-cell functions to experimentally induced urinary tract infections (UTI) with Escherichia coli. MATERIALS AND METHODS: Interferon-gamma (IFN-gamma), interleukin-4 (IL-4), IL-10, inducible nitric oxide synthase, T cell receptor (TCR) delta-chain and JHD B cell-deficient gene knockout mice and their immunocompetent controls were challenged with uropathogenic Escherichia coli. The bladders and kidneys were cultured for viable E. coli at time intervals after intraurethral challenge to assess susceptibility to an experimentally induced UTI. RESULTS: Knockout mice with gammadelta-T cell or IFN-gamma deficiencies were more susceptible to UTI than immunocompetent mice or mice with immunodeficiencies in IL-10, IL-4, inducible nitric oxide synthase or antibody production (JHD). CONCLUSIONS: These data support an important role for gammadelta-T cells and IFN-gamma in resistance to UTI in mice.

Animals↗
PubMed1999

Elevated tryptase, nerve growth factor, neurotrophin-3 and glial cell line-derived neurotrophic factor levels in the urine of interstitial cystitis and bladder cancer patients.

PURPOSE: The 2 prominent features of interstitial cystitis are pain and increased numbers of mast cells in the bladder. In this pilot study we determined the concentration of soluble mediators associated with activation of sensory neurons and/or mast cells that were present in the urine. MATERIALS AND METHODS: The study groups included 4 interstitial cystitis patients, 7 kidney donors with no history of bladder disease as negative controls, 6 bladder cancer patients and 7 patients with urinary tract infection as reference controls. Urine samples were assayed for different soluble mediators using immunoassays for tryptase (a marker for mast cell activation), neurotrophic factors (markers of neuronal plasticity) and chemokines (markers of inflammatory cell activity). Results were normalized based on creatinine concentration. RESULTS: There was a marked increase in the average amounts of tryptase and 3 neurotrophic factors in patient urine. Interestingly, the mediator profile in the urine of bladder cancer patients was indistinguishable from that of interstitial cystitis patients with respect to these same 4 proteins. There was no difference between normal control and urinary tract infection urine samples. CONCLUSIONS: These findings may account for several clinical and pathological features found in interstitial cystitis and bladder cancer. Although preliminary due to the limited numbers of patients, they also suggest that increased levels of neurotrophin-3, nerve growth factor, glial cell line-derived neurotrophic factor and tryptase in the urine could serve as a basis for adjunct diagnosis, monitoring and treatment of interstitial cystitis.

Adult↗
PubMed1998

Multiocular cystic renal cell carcinoma: implications for nephron sparing surgery.

Multilocular cystic renal cell carcinoma (MCRCC) is an uncommon type of cystic renal neoplasm with characteristic histologic findings and a good prognosis. Three cases are reported. One case involves enucleation of an MCRCC in a kidney donor with a 10-year follow-up and no recurrence in the transplant recipient. Nephron sparing surgery should be considered when the diagnosis of MCRCC is suspected preoperatively and confirmed intraoperatively.

Aged↗
PubMed1998

A comparative study of major histocompatibility complex and red blood cell antigen phenotypes as risk factors for recurrent urinary tract infections in women.

Recurrent urinary tract infections (RUTI) are a significant health problem for many women, and host characteristics that increase susceptibility are not completely defined. This study evaluated data from 99 patients to examine further the question of a possible association between major histocompatibility complex (MHC) or red blood cell (RBC) antigen phenotype and predisposition to RUTIs. MHC class I and II, ABO, and Lewis RBC phenotypes were determined serologically. The MHC class II phenotypes of 55 subjects were also determined by DNA polymerase chain reaction techniques. There were no significant differences in the proportions of HLA-A or -B antigen types between patients and controls, nor in the frequencies of serologically or DNA-defined HLA-DR or -DQ phenotypes. Patient ABO and Lewis RBC phenotypes were not statistically different than those for controls. Thus, the overall risk for women to develop RUTIs does not appear to be associated with any single HLA, ABO, or Lewis phenotype.

ABO Blood-Group System↗
PubMed1998

Time course and host responses to Escherichia coli urinary tract infection in genetically distinct mouse strains.

Recurrent urinary tract infections (UTIs) are a significant clinical problem for many women; however, host susceptibility factors have not been completely defined. The mouse model of induced UTI provides an experimental environment in which to identify specific host characteristics that are important in initial bacterial colonization of the urinary tract and in resolution of an infection. This study examined initial susceptibility, bacterial clearance, and host defense mechanisms during induction and resolution of Escherichia coli UTIs in genetically distinct strains of mice. Of the ten inbred strains tested, six (BALB/c, C3H/HeN, C57BL/6, DBA.1, DBA.2, and AKR) showed progressive resolution of bladder infections over a 14-day period. A constant, low-level bladder infection was observed in SWR and SJL mice. High bladder infection levels persisted over the 14-day study period in C3H/HeJ and C3H/OuJ mice. Kidney infection levels generally correlated with bladder infection levels, especially in C3H/HeJ and C3H/OuJ mice, the two most susceptible strains, in which infections became more severe with time after challenge. The degree of inflammation in bladder and kidneys, as well as antibody-forming cell responses, positively correlated with infection intensity in all strains except C3H/HeJ, which had minimal inflammation despite high infection levels. These results demonstrate two important aspects of host defense against UTI. First, the innate immune response to an infection in the bladder or kidneys consists primarily of local inflammation, which is followed by an adaptive response characterized in part by an antibody response to the infecting bacteria. Second, a UTI will be spontaneously resolved in most cases; however, in mice with specific genetic backgrounds, a UTI can persist for an extended length of time. The latter result strongly suggests that the presence or absence of specific host genes will determine how effectively an E. coli UTI will be resolved.

Animals↗
PubMed1998

In vitro passive sensitization of the ureter as a basis for the study of noninfectious ureteral inflammation.

PURPOSE: To develop an in vitro model of passive sensitization for the ureter for the study of noninfectious ureteral inflammation. MATERIALS AND METHODS: Human ureteral tissues were obtained from excess segments of ureters from patients undergoing donor nephrectomy. Following excision, ureters were placed in physiologic salt solution (PSS) and passively sensitized by incubating with ragweed serum from allergic donor (1 ml. serum: 4 ml. PSS) for 20 hours at room temperature. Ureteral segments were incubated with PSS only and served as non-sensitized controls (n = 4). After sensitization, excess serum was removed by serial washing with PSS without serum. Ureteral strips were then suspended in vitro for determination of tissue contraction. Contractile responses and histamine release were measured. Tissues were then exposed to antigen. To investigate the role of inflammatory mediators in tissue contraction, 4 groups of 8 sensitized ureteral segments were incubated for 1 hour with the following substances: a H1 histamine receptor antagonist (pyrilamine), an inhibitor of prostaglandin synthesis (indomethacin), an inhibitor of leukotriene synthesis (A-64077), and a control substance (DMSO). Following incubation, the tissues were exposed to antigen, and contraction and histamine release were determined. RESULTS: Sensitized ureteral segments (n = 8) responded to antigen with contraction (30% BaCl maximum; p <0.01) and histamine release (205/ng./gm. tissue) within the first 5 minutes of superfusion. Non-sensitized control segments (n = 4) did not respond. Both indomethacin and pyrilamine reduced (7-10% of BaCl maximum; p <0.05) the contractile response of sensitized ureter to antigen, whereas A-64077 did not. Analysis of the superfusate for histamine indicates that indomethacin reduced histamine release (150 ng./gm.) whereas A-64077 and pyrilamine did not (p <0.05). CONCLUSION: We have demonstrated that ureteral segments can be passively sensitized and that subsequent antigen challenge stimulates contraction and histamine release. Our findings suggest that contraction of ureteral tissue and histamine release may be utilized as an inherent bioassay indicating the activity of inflammatory mediators. In addition, these results suggest that both prostaglandins and histamine, but apparently not leukotrienes, participate in the early inflammatory response to antigen challenge of the sensitized ureter.

Antigens↗
PubMed1997

Vaginal mucosal immunization for recurrent urinary tract infection: phase II clinical trial.

PURPOSE: Decreased local immunity to uropathogenic bacteria may be a factor predisposing women to recurrent urinary tract infections. Our phase I study demonstrated the safety of a multi-strain vaccine administered as a vaginal suppository. A phase II study was conducted to determine vaccine efficacy. MATERIALS AND METHODS: A total of 91 women susceptible to recurrent urinary tract infections was entered into the study and the courses were analyzed in a randomized, double-blind, placebo controlled trial of vaginal mucosal immunization. Subjects received 3 vaginal suppositories at weekly intervals. Depending on the treatment group each suppository contained 1 of 2 vaccine doses or suppository material only. Each patient was followed for 5 months to record infection episodes, and obtain urine, vaginal irrigates and serum to measure immunological responses. RESULTS: Immunogen treated women who were off antibiotic prophylaxis throughout the study had a significant delay in interval to reinfection during the first 8 weeks compared to women receiving placebo. Mean interval until reinfection was delayed from 8.7 weeks for placebo treated to 13 weeks for vaccine treated women. Immunological responses in serum, urine and vaginal fluid were variable. No serious adverse effects were observed. CONCLUSIONS: These data demonstrate that vaginal mucosal immunization can enhance resistance to urinary tract infections in susceptible patients.

Adjuvants, Immunologic↗
PubMed1996

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↗