John Sedor

HOSPITAL-ACQUIRED URINARY TRACT INFECTIONS ASSOCIATED WITH THE INDWELLING CATHETER

Indwelling urethral catheters are commonly used in patients admitted to acute care hospitals. Forty percent of nosocomial infections occur in the urinary tract, and greater than 80% of these infections are secondary to an indwelling urethral catheter. Fortunately, the majority of catheters are left indwelling for a short period of time. The duration of catheterization is directly related to the development of bacteriuria, nosocomial infection, and possible bacteremia with sepsis. A relatively low percentage of patients become infected during the first 3 to 5 days if sterile technique and proper maintenance of a closed system are performed. Bacteria may grow in the urine (planktonic) and ascend via the lumen, or bacteria in the biofilm around the outside of the catheter may infect the bladder. Most organisms are from the patients intestinal flora, but exogenous sources on or near the patient may be involved. The major morbid events associated with the catheter are fever and the possible progression to bacteremia and sepsis. Early recognition of complications and arresting their progression, especially in the high-risk patient, are essential. Current research is directed at developing ways to reduce infection beyond the sterile closed system.

Loss of FHIT expression in transitional cell carcinoma of the urinary bladder

Cytogenetic and loss of heterozygosity (LOH) studies demonstrated chromosome 3p deletions in transitional cell carcinoma (TCC). We recently cloned the tumor suppressor gene FHIT (fragile histidine triad) at 3p14.2, one of the most frequently deleted chromosomal regions in TCC of the bladder, and showed that it is the target of environmental carcinogens. Abnormalities at the FHIT locus have been found in tumors of the lung, breast, cervix, head and neck, stomach, pancreas, and clear cell carcinoma of the kidney. We examined six TCC derived cell lines (SW780, T24, Hs228T, CRL7930, CRL7833, and HTB9) and 30 primary TCC of the bladder for the integrity of the FHIT transcript, using reverse transcriptase-polymerase chain reaction (RT-PCR) to investigate a potential role of the FHIT gene in TCC of the bladder. In addition, we tested expression of the Fhit protein in the six TCC-derived cell lines by Western blot analysis and in 85 specimens of primary TCCs by immunohistochemistry. Three of the six cell lines (50%) did not show the wild-type FHIT transcript, and Fhit protein was not detected in four of the six cell lines (67%) tested. Fhit expression also was correlated with pathological and clinical status. A significant correlation was observed between reduced Fhit expression and advanced stage of the tumors. Overall, 26 of 30 (87%) primary TCCs showed abnormal transcripts. Fhit protein was absent or greatly reduced in 61% of the TCCs analyzed by immunohistochemistry. These results suggested that loss of Fhit expression may be as important in the development of bladder cancer as it is for other neoplasms caused by environmental carcinogens.

THE URINARY GLYCOPROTEIN GP51 AS A CLINICAL MARKER FOR INTERSTITIAL CYSTITIS

PURPOSEnGP51 is a urinary glycoprotein with a molecular weight of 51 kDa. This glycoprotein is produced and secreted by the transitional epithelium of the genitourinary tract, and has been isolated from human urine. Studies have demonstrated that GP51 levels are decreased in bladder biopsies of patients with interstitial cystitis. We evaluated urinary GP51 in a noninvasive manner as a clinical marker of interstitial cystitis.nnnMATERIALS AND METHODSnUrinary GP51 levels were measured using antigen inhibition enzyme-linked immunosorbent assay. In blinded fashion we analyzed for quantitative differences 24-hour urine samples of 36 patients with interstitial cystitis and 23 normal controls who were age matched within 5 years (mean age 47.3). We also evaluated GP51 in random urine specimens of 17 normal controls, 14 patients with interstitial cystitis and 11 subjects who had undergone cystectomy to determine whether urinary GP51 is mainly produced by the bladder, which is the site of interstitial cystitis. To ascertain the specificity of urinary GP51 to interstitial cystitis urine samples of 34 patients with other urological diseases were measured and compared with findings in the samples of 15 with interstitial cystitis.nnnRESULTSnLow GP51 levels appeared to be unique to the interstitial cystitis state compared to normal (p = 0.008). GP51 in patients with interstitial cystitis and in those who underwent cystectomy was lower (p < 0.001) than in normal controls. These findings suggest that the major source of urinary GP51 is the bladder. Also, we observed lower GP51 levels in interstitial cystitis than in other urinary tract diseases (p < 0.0001).nnnCONCLUSIONSnOur study substantiates the possibility of using GP51 as a clinical marker for diagnosing interstitial cystitis by a noninvasive urinary assay.

Intravesical Capsaicin in Neurologic Impaired Patients With Detrusor Hyperreflexia

Capsaicin is known to be neurotoxic for C-fiber afferents. We investigated the intravesical application of capsaicin in the treatment of detrusor hyperreflexia (DH) in seven patients (ages 23-52) with neurologic impairment. The patients were evaluated with both ice-water cystometry and formal video-urodynamic studies. Four biweekly courses of intravesical capsaicin treatment were administered using increasing concentrations (100 microM, 500 microM, 1 mM, and 2 mM). Treatment effect was monitored using a bladder diary and urodynamic evaluation one month after capsaicin treatment. Prior to treatment, six of the seven patients demonstrated a positive ice-water test and DH. Two patients were not able to complete the study due to discomfort attributed to capsaicin. Five of the seven patients completed the four courses of increasingly concentrated capsaicin. Three patients noted symptomatic improvement while two did not. The mean urodynamic bladder capacity significantly increased from 124 +/- 39 ml pre-capsaicin to 231 +/- 62 ml one month post-capsaicin in the three patients with symptomatic improvement (p < 0.05). Urodynamic testing revealed that one of the six patients with a positive ice-water test lost that response after intravesical capsaicin. Intravesical capsaicin is a novel and promising treatment for detrusor hyperreflexia in neurologically impaired patients.

Antisperm antibodies in seminal plasma of spinal cord-injured men.

Central to the problem of reproductive rehabilitation of spinal cord-injured men treated by assisted ejaculatory techniques is the consistent observation of deficient semen quality. Most studies have reported asthenospermia despite the presence of normal sperm concentration in most men undergoing these procedures. To date little attention has been given to the incidence and relevance of sperm autoimmunity in this group. In 9 anejaculatory spinal cord-injured men, electroejaculation was performed. Antegrade ejaculates were obtained in 7 men and analyzed. Mean sperm antegrade concentration was 74.4 +/- 113 x 10(6)/mL with a mean motile sperm concentration of 28.6 +/- 54.0 x 10(6)/mL. Enzyme-linked immunosorbent assay (ELISA)-determined antisperm antibody response was positive in the seminal plasma of 5 of 7 patients. Because of the disproportionately high incidence of an immunologic factor in men with neurogenic infertility, sperm autoimmunity should be considered among the important causes underlying their seminal dysfunction.

Are sperm motion parameters influenced by varicocele ligation

OBJECTIVEnTo document objectively, improvements in sperm motion parameters in subfertile men after varicocele ligation with the use of computer-aided sperm analysis.nnnDESIGNnRetrospective chart review.nnnSETTINGnAn academic clinical environment.nnnPATIENT(S)nThirty-four men with varicocele as the primary cause of infertility who underwent a physical examination, hormonal profile, and Doppler ultrasound evaluation.nnnINTERVENTION(S)nComputer-aided sperm analysis was performed before and after either subinguinal or laparoscopic varicocele ligation.nnnMAIN OUTCOME MEASURE(S)nPatients were followed up for 3-18 months after operation, and average computer-aided sperm analysis values were obtained before and after operation. Computer-aided sperm analysis values were analyzed by paired Students t-test, with special reference to motility and sperm motion parameters.nnnRESULT(S)nAfter varicocele ligation, patients demonstrated increases in mean sperm density and in the overall distribution of sperm with rapid velocity, although the increases were not statistically significant. Mean measures of straightness, linearity, and track speed also were increased after operation, but only progressive sperm velocity was increased to a statistically significant level.nnnCONCLUSION(S)nBecause progressive velocity has been a primary computer-aided sperm analysis parameter predictive of male fertility and the success of assisted reproductive techniques, we conclude that varicocele ligation results in improvements in semen parameters, especially the key parameter of progressive sperm velocity.

Evaluation of sperm morphology of electroejaculates of spinal cord-injured men by strict criteria *

OBJECTIVEnTo compare sperm morphology of electrostimulated ejaculates of spinal cord-injured (SCI) men with that of manual ejaculates of an able-bodied population.nnnDESIGNnRetrospective study.nnnPATIENTSnSpinal cord-injured men (n = 21) participating in a reproductive rehabilitation program and able-bodied men (n = 163) attending a male fertility clinic.nnnSETTINGnMale fertility clinic of a university urology practice.nnnMAIN OUTCOME MEASURESnMorphological characteristics of sperm evaluated by strict criteria.nnnRESULTSnElectroejaculates of SCI men had significantly higher percentages of small sperm heads, vacuolated sperm heads, and sperm with tail defects than found in manual ejaculates of able-bodied men. Cellular elements of nongerminal origin (white blood cells, red blood cells, epithelial cells) were also more likely to be present in electroejaculates.nnnCONCLUSIONnWhen evaluated by strict criteria, electroejaculates exhibit specific defects in sperm morphological profile. A pervasive pattern of teratozoospermia exists that may reflect underlying defects contributing to decreased fertility in SCI men.

INTERACTION OF BLADDER GLYCOPROTEIN GP51 WITH UROPATHOGENIC BACTERIA

PURPOSEnA major component of bladder surface mucin is a glycoprotein GP51 (molecular weight 51 kD.). GP51, which has previously been isolated from rabbit mucosa, appears to function as part of the defense mechanism in an in vivo infection model. GP51 coats the epithelium and is secreted into the urine, as detected by immunohistochemical testing and enzyme-linked immunosorbent assay (ELISA). Increased urinary GP51 occurs during urinary tract infection. To elucidate the role of GP51 as a component of the primary defense mechanism we studied interactions with uropathogenic bacterial isolates and urine from symptomatic patients with urinary tract infection.nnnMATERIALS AND METHODSnELISA was performed to demonstrate the binding of GP51 and various uropathogens. Immunochemical studies were done using monoclonal antibodies to GP51 to determine the interaction of GP51 with certain uropathogenic isolates, including Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, Proteus vulgaris, Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus aureus, S. epidermidis and Streptococcus faecalis. Infected urinary sediments and uropathogenic bacterial cultures were examined by immunocytochemical testing to localize GP51. Antigen inhibition ELISA was done to quantitate urinary GP51 in the urine of 17 normal controls and 19 patients with urinary tract infection.nnnRESULTSnELISA revealed that GP51 binds to a wide spectrum of gram-positive and gram-negative uropathogens in semiquantitative fashion. Immunochemical methods confirmed that purified GP51 binds to bacteria, encapsulating and aggregating the bacteria. Clinical specimens showed GP51 localized to bacteria and uroepithelial cells. We observed a significant increase in urinary GP51 in urinary tract infection compared to uninfected urine (p = 0.0003).nnnCONCLUSIONSnThese studies suggest that GP51, a component of bladder mucin, may be a strategic factor in the primary defense mechanism of the bladder.

Systemic sperm autoimmunity in spinal-cord injured men

Historically, spinal-cord injured men have been considered virtually sterile because of ejaculatory dysfunction commonly resulting from their injury. Assisted ejaculatory techniques, however, have overcome the problem of sperm transport and have allowed both the establishment of pregnancy through artificial insemination and the assessment of their semen quality. Most studies have noted the presence of asthenozoospermia in the setting of normal sperm concentration following electroejaculation or vibratory stimulated ejaculation. Thus far, little attention has been given to the basis for the frequent finding of asthenozoospermia, and the possibility of sperm autoimmunity in this group has not been adequately studied. In nine spinal-cord injured men, reproductive evaluation was performed consisting of hormonal measurements, testicular biopsy, and indirect immunobead tests for sperm autoimmunity. A mean sperm concentration was 144 +/- 185 x 10(6)/ml. However, the mean motile concentration was 33 +/- 62 x 10(6)/ml. Indirect serum immunobead showed positive IgG or IgA titers in 3 of 8 patients. Because of the disproportionately high incidence of an immunologic factor in spinal-cord injured men compared to able-bodied infertile men, sperm autoimmunity should be considered among the important causes underlying seminal dysfunction following spinal cord injury.