Intravesical Escherichia coli lipopolysaccharide stimulates an increase in bladder nerve growth factor.

OBJECTIVE: To investigate the effects of the intravesical instillation of Escherichia coli lipopolysaccharide (LPS) on nerve growth factor (NGF, which may mediate the pain associated with inflammation) protein and mRNA in the bladders of mice. MATERIALS AND METHODS: E. coli LPS was instilled into the bladders of female mice; the whole-bladder NGF content was then determined by an enzyme-linked immunosorbent assay and the NGF mRNA content of the bladder determined by semiquantitative reverse transcription-polymerase chain reaction. Bladder NGF was also evaluated by immunohistochemistry in some of the mice. RESULTS: LPS stimulated a significant increase in bladder NGF 90 min after instillation, but bladder NGF content was significantly less than that in bladders of control mice 3 and 7 h after LPS instillation. Twenty-four hours after the intravesical infusion of saline or LPS, there was no difference in NGF content in bladders from saline or LPS-infused mice. Immunohistochemistry confirmed the presence of increased NGF in the mucosa of detrusor from bladders 90 min after LPS instillation. Bladder NGF mRNA increased more slowly in response to LPS, and 7 and 24 h after LPS instillation the relative abundance of NGF mRNA was 1.5 and 2.0 times greater in LPS-infused bladders, respectively. CONCLUSIONS: E. coli LPS can stimulate increased NGF message and protein in the bladder. The increase in NGF protein preceded the increase in mRNA, suggesting that this increase was not the result of gene transcription. It is possible that NGF participates in the pathogenesis of pain associated with bacterial cystitis.

Two general routes to 1,4-disubstituted-2,3,4,5-tetrahydro- 1H-3-benzazepines.

[structure] Two general routes to 1,4-disubstituted-2,3,4, 5-tetrahydro-1H-3-benzazepines are described. Both routes utilize an appropriately functionalized phenethylamino alcohol as the penultimate intermediate: the first route makes use of the reductive amination of a benzyl alkyl ketone with alpha-(aminomethyl)benzyl alcohol, while the second route utilizes the addition of a Grignard reagent to the oxazolidine derived from a substitued phenylacetaldehyde and alpha-(methylaminomethyl)benzyl alcohol. In all cases studied, the cis-1,4-disubstituted-2,3,4, 5-tetrahydro-1H-3-benzazepine was obtained as the major product.

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.

Removal of retained Penrose drain under fluoroscopic guidance.

An uncommon complication of Penrose drain usage is retention of the drain by a fascial suture. Removal of a retained Penrose drain can be carried out percutaneously under fluoroscopic guidance.

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.

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.

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.

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.