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Biomedical subjects

A J Schaeffer

Publications and source records attributed to A J Schaeffer.

At least 19 recordsLinked to original sources
PubMed2001

Secretory IGA differentially promotes adherence of type 1-piliated Escherichia coli to immortalized vaginal epithelial cell lines.

OBJECTIVES: To elucidate the factors that influence bacterial adherence to vaginal epithelium. We developed an in vitro model to examine the interaction of type 1-piliated Escherichia coli, strain HB101/p1-17, with immortalized vaginal epithelial cells (VEC) from postmenopausal donors with (patient 1) and without (patient 2) clinical histories of urinary tract infections (UTI). METHODS: The VEC were incubated in microtiter plates in the presence of E. coli HB101/p1-17, and factors such as time, mannose concentration, and secretory immunoglobulin A (sIgA) concentration were assessed. After incubation, the numbers of bacteria bound per VEC were counted on a scintillation counter. RESULTS: The E. coli adhered to the VEC and the adherence was inhibited in the presence of 100-mM mannose solution. Clinical donor UTI histories were reflected in the binding characteristics of the VEC cell lines, with cells from patient 1 having a 30% higher baseline binding capacity than cells from patient 2 and an enhanced binding response in the presence of increasing sIgA concentrations. The sIgA concentration did not affect the patient 2 cell-bacterial binding. CONCLUSIONS: These results indicate that our in vitro model is suitable for studying the factors influencing bacterial adherence to vaginal mucosa, and that after immortalization, vaginal mucosa maintains clinically relevant characteristics that can be studied. Our data suggest that E. coli adherence to vaginal mucosa from postmenopausal women susceptible to UTI is affected by intrinsic baseline bacterial binding capacity of the mucosa cells as well as by increased sIgA concentration in the women's vaginal fluid. Increasing vaginal fluid sIgA concentration in this population may have a deleterious rather than beneficial effect.

Bacterial Adhesion↗
PubMed2001

Host pathogenesis in urinary tract infections.

Urinary tract infections (UTIs) are the result of an interaction between bacterial virulence and host defense factors that compete to invade or protect the host, respectively. Research over the past 30 years has demonstrated that vaginal colonization with uropathogens precedes most UTIs. Receptivity of the vaginal mucosa for uropathogens is an essential initial step in vaginal mucosa colonization. When vaginal and buccal epithelial cells were collected from patients susceptible to reinfection and compared with such cells obtained from controls resistant to UTIs, the strains that caused cystitis adhered much more avidly to the epithelial cells from susceptible women. These genotypic traits for epithelial cell receptivity may be a major susceptibility factor in UTIs. The presence or absence of blood group determinants on the surface of uroepithelial cells may influence an individual's susceptibility to UTIs. The protective effect in women with the secretor phenotype may be due to fucosylated structures at the cell surface which decrease the availability of putative receptors for Escherichia coli. Susceptibility among women who do not secrete blood group antigens may be due to specific E. coli-binding glycolipids that are absent in women who secrete blood group antigens. Recent studies have shown that the vaginal fluid, which forms an interface between uropathogens and epithelial cells, also influences vaginal colonizations.

Bacterial Adhesion↗
PubMed2000

Biofeedback, pelvic floor re-education, and bladder training for male chronic pelvic pain syndrome.

OBJECTIVES: Pelvic floor tension myalgia may contribute to the symptoms of male patients with chronic pelvic pain syndrome (CPPS). Therefore, measures that diminish pelvic floor muscle spasm may improve these symptoms. Based on this hypothesis, we enrolled 19 patients with CPPS in a 12-week program of biofeedback-directed pelvic floor re-education and bladder training. METHODS: Pre-treatment and post-treatment symptom assessments included daily voiding logs, American Urological Association (AUA) symptom score, and 10-point visual analog pain and urgency scores. Pressure-flow studies were obtained before treatment in most patients. Instruction in pelvic floor muscle contraction and relaxation was achieved using a noninvasive form of biofeedback at biweekly sessions. Home exercises were combined with a progressive increase in timed-voiding intervals. RESULTS: Mean age of the 19 patients was 36 years (range 18 to 67). Four patients completed less than three treatment sessions, 5 patients completed three to five sessions, and 10 attended all six sessions. Mean follow-up was 5.8 months. Median AUA symptom scores improved from 15.0 to 7.5 (P = 0.001), and median bother scores decreased from 5.0 to 2.0 (P = 0.001). Median pain scores decreased from 5.0 to 1.0 (P = 0.001), and median urgency scores decreased from 5.0 to 2.0 (P = 0.002). Median voiding interval increased from 0.88 hours to 3.0 hours (P = 0.003). Presence of detrusor instability, hypersensitivity to filling, or bladder-sphincter pseudodyssynergia on pretreatment urodynamic studies was not predictive of treatment results. CONCLUSIONS: This preliminary study confirms that a formalized program of neuromuscular re-education of the pelvic floor muscles together with interval bladder training can provide significant and durable improvement in objective measures of pain, urgency, and frequency in patients with CPPS.

Adolescent↗
PubMed2000

Evaluation of the cytokines interleukin 8 and epithelial neutrophil activating peptide 78 as indicators of inflammation in prostatic secretions.

OBJECTIVES: Chronic prostatitis/chronic pelvic pain syndrome (CPPS) is a disorder characterized by pelvic pain and varying degrees of inflammation exhibited in expressed prostatic secretions (EPS). To provide objective parameters of inflammation, we measured the cytokines interleukin 8 (IL-8) and epithelial neutrophil activating peptide 78 (ENA-78) in EPS of healthy men, men with benign prostatic hyperplasia (BPH), men with bacterial prostatitis (BP), and men with chronic prostatitis/CPPS. METHODS: Enzyme-linked immunosorbent assays of the EPS for IL-8 and ENA-78 were done in 63 men: control (n = 9), BPH (n = 6), BP (n = 3), inflammatory CPPS (National Institutes of Health [NIH] category IIIa) (n = 17), noninflammatory CPPS (NIH category IIIb) (n = 17), and asymptomatic inflammatory prostatitis (NIH category IV) (n = 11). RESULTS: IL-8 was detectable in all patients, and ENA-78 was detectable in all except 2 patients (threshold of detection 10 pg/mL for IL-8, 15 pg/mL for ENA-78). Mean levels of IL-8 [ENA-78] were similar in control (3010 pg/mL [423 pg/mL]), BPH (3341 pg/mL [98 pg/mL]), and IIIb (2751 pg/mL [335 pg/mL]) groups. Both cytokine levels were higher in BP (11,175 pg/mL [13,761 pg/mL]), IIIa (10,418 pg/mL [2240 pg/mL]), and IV (8571 pg/mL [1865 pg/mL]) groups. A statistically significant difference between the control group versus BP, IIIa, and IV (P <0.05) groups was found for IL-8 but not for ENA-78. CONCLUSIONS: IL-8 and ENA-78 are frequently elevated in the EPS of men with BP, CPPS IIIa, and asymptomatic inflammatory prostatitis category IV. These cytokines are direct mediators of leukocyte accumulation and activation at inflammatory sites and may be responsible, in part, for the presence of inflammatory reaction in the prostate.

Adult↗
PubMed2000

A prospective study of interstitial cystitis: results of longitudinal followup of the interstitial cystitis data base cohort. The Interstitial Cystitis Data Base Study Group.

PURPOSE: We present baseline characteristics and longitudinal profiles of symptoms in the Interstitial Cystitis Data Base study, a prospective cohort study of patients with interstitial cystitis. MATERIALS AND METHODS: A total of 637 eligible patients were entered into the study and followed for symptoms of pain, urgency and urinary frequency. Median followup was 31 months. RESULTS: More than 90% of patients were white women with a median age of 43 years. Using the overall pain-urgency-frequency score 7% of participants presented with mild, 44% with moderate and 49% with severe symptoms. Severe urgency in 41% of cases and severe 24-hour frequency in 41% were more common than severe pain in 29%. Of the patients 51% reported nighttime frequency of 2 or more voids. Median duration of interstitial cystitis symptoms was 8 years and 68% of participants were previously diagnosed with the condition. The 36% of patients who withdrew from study or were lost to followup were more likely to have had more severe symptoms at baseline. Patterns of change with time suggest initial symptom improvement due to regression to the mean, and an intervention effect associated with the increased followup and care of cohort participants. Although all symptoms fluctuated, there was no evidence of significant long-term change in overall disease severity. CONCLUSIONS: Our observations support the clinical observation that interstitial cystitis is a chronic disease and no current treatments have a significant impact on symptoms with time. These results provide a foundation for the design and performance of future clinical trials in interstitial cystitis using these end points in a similar patient population.

Adolescent↗
PubMed2000

Evaluation of the bacterial flora of the prostate using a 16S rRNA gene based polymerase chain reaction.

PURPOSE: The role of bacteria in the chronic pelvic pain syndrome (nonbacterial prostatitis and prostatodynia) is controversial and difficult to assess because the bacterial flora of the prostate is not well defined. Polymerase chain reaction (PCR) is a highly sensitive molecular method of bacterial detection. It confirms the sterility of tissue with a high level of confidence and detects small numbers of microbial agents that may represent pathogens. We performed PCR to determine bacterial colonization of the prostate in presumably healthy men and in those undergoing simple or radical prostatectomy. MATERIALS AND METHODS: We analyzed 28 prostate samples from 18 organ donors from whom prostate tissue was obtained under sterile surgical conditions at organ withdrawal, 14 sterile surgical prostate specimens from 7 patients undergoing radical prostatectomy for prostate cancer who previously underwent transrectal biopsy and 6 sterile surgical specimens from 2 men who underwent simple prostatectomy for benign prostatic hyperplasia (BPH), including 1 with an indwelling catheter for several weeks. For PCR we used 2 sets of primers to detect bacterial 16S rRNA gene sequences. Normal prostate tissue seeded in vitro with known numbers of Escherichia coli was used to assess the sensitivity of PCR. RESULTS: Only 3 of the 28 organ donor samples had histological signs of minimal inflammation and all other samples appeared to be normal without evidence of inflammatory reaction. All of these samples were PCR negative. Of several PCR control reactions the mixture of prostate tissue seeded with known numbers of E. coli demonstrated the high sensitivity of the assay, allowing the detection of as few as 6 bacteria in the presence of 25 mg. of prostate tissue. A focal and heterogeneous distribution of inflammation and infection was noted in the 14 radical prostatectomy specimens. In the prostate cancer and BPH groups there was a strong association of inflammation with positive PCR findings. Of 11 samples 3 without but all 9 with inflammation were PCR positive. CONCLUSIONS: PCR is a highly sensitive method for detecting bacteria in the prostate. In our study negative PCR reactions in the prostate tissue of apparently healthy men made the presence of normal bacterial flora in the prostate extremely unlikely. The presence of bacteria and/or inflammation in radical prostatectomy specimens was found to be a localized process. Concordance between inflammation and positive PCR results in simple and radical prostatectomy specimens suggests that bacteria may frequently have a role in histologically inflammatory prostatitis.

Adolescent↗
PubMed2000

Characterization of an immortalized human vaginal epithelial cell line.

PURPOSE: Adherence of type 1 piliated Escherichia coli to vaginal mucosa plays a major role in the pathogenesis of ascending urinary tract infections (UTIs) in women. Progress in understanding the mechanism of adherence to the vaginal surface could be enhanced by the utilization of well-characterized vaginal epithelial cells. The objective of this study was to immortalize vaginal epithelial cells and study their bacterial adherence properties. MATERIALS AND METHODS: Primary vaginal cells were obtained from a normal post-menopausal woman, immortalized by infection with E6/E7 genes from human papillomavirus 16 (HPV 16) and cultured in serum free keratinocyte growth factor medium. RESULTS: Positive immunostaining with a pool of antibodies to cytokeratins 1, 5, 10 and 14 (K1, K5, K10 and K14) and to K13 confirmed the epithelial origin of these cells. The immortalized cells showed binding of type 1 piliated E. coli in a pili specific and mannose sensitive manner. CONCLUSION: This model system should facilitate studies on the interaction of pathogens with vaginal mucosal cells, an essential step in the progression of ascending UTIs in women.

Bacterial Adhesion↗
PubMed2000

IL-1beta and TNF-alpha in prostatic secretions are indicators in the evaluation of men with chronic prostatitis.

PURPOSE: Chronic Prostatitis, or Chronic Pelvic Pain Syndrome [CPPS], is a common disorder characterized by pelvic pain and varying degrees of inflammation in expressed prostatic secretions (EPS). In search of markers to more clearly define CPPS, we compared proinflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) levels in EPS from men with CPPS, to healthy men and men with Benign Prostatic Hyperplasia (BPH). METHODS: 78 men: controls (n = 16), BPH (n = 14), CPPS IIIA [>/=10 white blood cells per high power field (WBC/hpf) in EPS] (n = 18), CPPS IIIB [<10 WBC/hpf in EPS] (n = 20), and asymptomatic inflammatory prostatitis (AIP) (n = 10) were evaluated for EPS WBC, and IL-1beta and TNF-alpha by ELISA. RESULTS: IL-1beta and TNF-alpha levels in EPS were usually detectable in men with CPPS IIIA (89% and 45%, respectively) or AIP (90%; 100%), but less often in controls (31%; 17%), BPH (57%; 15%), and CPPS IIIB (35%; 15%) respectively. IL-1beta and TNF-alpha levels were higher in CPPS IIIA versus CPPS IIIB, and in AIP versus controls or BPH (p's <0.001). Cut-points for IL-1beta and TNF-alpha discriminated AIP from controls (predictive values = 94% and 83%, respectively) and CPPS IIIA from CPPS IIIB (predictive values 84% and 100%). Overall, there was a correlation between IL-1beta and TNF-alpha (p <0.003), but no correlation between WBC and IL-1beta (p <0.1) or TNF-alpha (p <0.50). CONCLUSIONS: Cytokines are frequently present and elevated in the EPS from men with CPPS IIIA and AIP and provide a novel means for identification, characterization and potential management of men with CPPS that differs from traditional methods based on WBC.

Adult↗
PubMed1999

Questionnaire based results of the bulbourethral sling procedure.

PURPOSE: The success rate of the bulbourethral sling procedure to treat post-radical prostatectomy incontinence has been reported in a previous chart review analysis. We present further evaluation of the procedure using postoperative mailed questionnaires. MATERIALS AND METHODS: Between October 1994 and October 1997, 66 men underwent the bulbourethral sling procedure at our hospital. Postoperatively all patients with indwelling bolsters were mailed questionnaires to assess continence status, discomfort and voiding patterns. RESULTS: Of the 66 patients 4 required bolster removal for infection (2), erosion (1) or pain (1), and 1 died. These patients were not assessed further. Questionnaire data were obtained from the remaining 61 patients. At a median followup of 9.6 months (mean 11.9, range 3 to 30) 25 patients (41%) reported complete cure of incontinence, 32 (53%) required no pad for protection and 52 (85%) required 2 pads or less. Persistent perineal numbness or discomfort was present in 32 patients (52%). Of 12 patients who received adjuvant radiation therapy only 1 (8%) was cured. CONCLUSIONS: The short-term success rate following the bulbourethral sling procedure is high but persistent perineal discomfort is common. Adjuvant radiation predisposes to treatment failure.

Aged↗
PubMed1999

Urodynamic analysis of the bulbourethral sling procedure.

PURPOSE: The bulbourethral sling procedure is successful in correcting incontinence following radical prostatectomy. However, the mechanism of action of the sling is not intuitively clear. We analyze the results of urodynamic testing on a cohort of men who underwent the bulbourethral sling procedure. MATERIALS AND METHODS: Between October 1994 and October 1997, 66 men underwent the bulbourethral sling procedure at our hospital. All but 1 patient underwent preoperative video urodynamic testing. Intraoperative urethral pressure profilometry and abdominal leak point pressure measurements were performed. Additionally, all patients were invited to undergo followup video urodynamic testing. Results were correlated with current continence status. RESULTS: Preoperatively all patients demonstrated intrinsic sphincter deficiency. Following sling placement postoperative Valsalva leak point pressure values were significantly increased but maximum resting urethral pressures were unchanged. Preoperative and postoperative Abrams-Griffiths nomograms were not consistent with postoperative bladder outlet obstruction. Postoperative voiding pressures were consistently less than corresponding Valsalva leak point pressures. CONCLUSIONS: Patients undergoing video urodynamic testing following the bulbourethral sling procedure demonstrated unobstructed voiding patterns, despite significant increases in Valsalva leak point pressures.

Humans↗
PubMed1999

Prostatitis: US perspective.

The diagnosis and management of prostatitis syndromes is a challenge to the clinician. Careful history and examination of the prostate fluid and quantitative segmented bacteriologic cultures will lead to proper categorization into the recognized forms of the prostatitis syndrome. Antimicrobial therapy is effective in the majority of men with acute and chronic bacterial prostatitis (CBP). Fluoroquinolone agents appear to have an increasingly important role in this regard, although a randomized, prospective, double-blind study is still lacking. Alpha-1-selective blocking agents may relieve symptomatology of chronic pelvis pain syndrome (CPPS). Other non-prostatic sources of voiding symptoms should be sought and ruled out, especially malignancy or inflammatory disorders.

Adolescent↗
PubMed1999

Guidelines for antimicrobial treatment of uncomplicated acute bacterial cystitis and acute pyelonephritis in women. Infectious Diseases Society of America (IDSA).

This is part of the series of practice guidelines commissioned by the Infectious Diseases Society of America (IDSA) through its Practice Guidelines Committee. The purpose of this guideline is to provide assistance to clinicians in the diagnosis and treatment of two specific types of urinary tract infections (UTIs): uncomplicated, acute, symptomatic bacterial cystitis and acute pyelonephritis in women. The guideline does not contain recommendations for asymptomatic bacteriuria, complicated UTIs, Foley catheter-associated infections, UTIs in men or children, or prostatitis. The targeted providers are internists and family practitioners. The targeted groups are immunocompetent women. Criteria are specified for determining whether the inpatient or outpatient setting is appropriate for treatment. Differences from other guidelines written on this topic include use of laboratory criteria for diagnosis and approach to antimicrobial therapy. Panel members represented experts in adult infectious diseases and urology. The guidelines are evidence-based. A standard ranking system is used for the strength of the recommendation and the quality of the evidence cited in the literature reviewed. The document has been subjected to external review by peer reviewers as well as by the Practice Guidelines Committee and was approved by the IDSA Council, the sponsor and supporter of the guideline. The American Urologic Association and the European Society of Clinical Microbiology and Infectious Diseases have endorsed it. An executive summary and tables highlight the major recommendations. Performance measures are described to aid in monitoring compliance with the guideline. The guideline will be listed on the IDSA home page at http://www.idsociety.org It will be evaluated for updating in 2 years.

Acute Disease↗