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John W Warren

Publications and source records attributed to John W Warren.

5 recordsLinked to original sources

Dysuria at onset of interstitial cystitis/painful bladder syndrome in women.

OBJECTIVES: In an ongoing national study of women to identify risk factors for interstitial cystitis/painful bladder syndrome (IC/PBS), dysuria was identified at the onset of IC/PBS in a small majority and the evidence for urinary tract infection was evaluated. METHODS: In women with IC/PBS of 12 months' duration or less, symptoms and pertinent laboratory tests at onset were assessed by telephone interview and medical record review. RESULTS: Of 138 women, 75 (54%) reported that they had started to experience burning or pain on urination at the onset of IC/PBS. Of those with urine cultures, 12 (34%) of 35 women with dysuria versus 1 (5%) of 21 without dysuria yielded a uropathogen (P = 0.01). Similarly, the microscopic white blood cell count and dipstick nitrites and leukocyte esterase were each significantly more common in the urine samples of those with dysuria than in those without. Additionally, 7 of 75 of those with dysuria versus 1 of 62 without dysuria reported chills or fever at the onset of IC/PBS. Using various definitions, the prevalence of urinary tract infection at the onset of IC/PBS, at a minimum, was 16% to 33% of those with dysuria versus less than 2% of those without dysuria (P < or = 0.003). CONCLUSIONS: A slight majority of women with IC/PBS reported dysuria at onset of their IC/PBS symptoms. The available laboratory data have suggested that dysuria may be a sensitive indicator of urinary tract infection at the onset of IC/PBS; however, its specificity is as yet undetermined.

Adult↗

Using the International Continence Society's definition of painful bladder syndrome.

OBJECTIVES: To determine what proportion of patients with recent-onset interstitial cystitis (IC)/painful bladder syndrome (PBS) met the International Continence Society (ICS) definition and how those who met the definition differed from those who did not. METHODS: We recruited women who had recent-onset IC/PBS for an ongoing case-control study to identify its risk factors and studied our first 138 eligible patients to identify those who met the ICS definition. We then compared those who met the definition with those who did not by variables acquired from interviews and medical records. RESULTS: The 138 participants had intensities of pain, urgency, frequency, and nocturia, as well as O'Leary-Sant Symptom Index scores, similar to those of previously reported patients with IC/PBS. Six percent of cystoscopies demonstrated Hunner's ulcers, and 89% of hydrodistensions under anesthesia revealed glomerulations. The most liberal interpretation of the ICS definition did not include 47 (34%) of our patients. Comparing these with the 91 (66%) who did meet the ICS criteria, we found that 96 of 97 clinical variables, including many generally thought to be characteristic of IC/PBS, were not significantly different between the two groups. CONCLUSIONS: The ICS definition identified only 91 (66%) of the 138 patients whom study investigators and caregivers diagnosed as having IC/PBS. Furthermore, those who met the ICS definition did not differ in important ways from those who did not. These observations taken together suggest that the ICS definition may not be sufficiently sensitive. Minor modifications of the definition appeared to increase its sensitivity. Validation of a case definition (ie, assessing its sensitivity and specificity) would require testing it in patients with IC/PBS, as well as in patients with other diseases with similar symptoms.

Adult↗

Prevalence of interstitial cystitis in first-degree relatives of patients with interstitial cystitis.

OBJECTIVES: To compare, in a pilot study, the prevalence of interstitial cystitis (IC) among first-degree relatives of patients with IC with the prevalence of IC in the general population. Often the first evidence that a disease may have a genetic susceptibility is the demonstration of family aggregation of the disease. METHODS: Members of the Interstitial Cystitis Association (ICA) were mailed a survey inquiring about the prevalence of the disease or consistent symptoms in first-degree family members (parents, siblings, and/or children). The same survey instrument was used in telephone interviews of a randomly selected sample of nonrespondents to determine the degree of responder bias. RESULTS: Of 2581 respondents to the mail-in survey, 101 (3.9%) reported 107 first-degree relatives with IC. The subsequent telephone interviews with 346 randomly selected nonrespondents revealed little selection bias in the mail-in survey. These measurements, plus data-based assumptions of proportions of those self-reporting IC who actually met the hydrodistension requirements for the diagnosis of IC, suggest that women, 31 to 73 years old who were first-degree relatives of patients with IC, themselves had a prevalence of IC of 995/100,000. A comparison of this with the number approximating the prevalence in the general population of American women of this age (60/100,000) indicates a risk ratio for IC in adult female first-degree relatives of 17. CONCLUSIONS: Adult female first-degree relatives of patients with IC may have a prevalence of IC 17 times that found in the general population. This, together with previously reported evidence showing a greater concordance of IC among monozygotic than dizygotic twins, suggests, but does not prove, a genetic susceptibility to IC.

Adult↗

Development of an intranasal vaccine to prevent urinary tract infection by Proteus mirabilis.

Proteus mirabilis commonly infects the complicated urinary tract and is associated with urolithiasis. Stone formation is caused by bacterial urease, which hydrolyzes urea to ammonia, causing local pH to rise, and leads to the subsequent precipitation of magnesium ammonium phosphate (struvite) and calcium phosphate (apatite) crystals. To prevent these infections, we vaccinated CBA mice with formalin-killed bacteria or purified mannose-resistant, Proteus-like (MR/P) fimbriae, a surface antigen expressed by P. mirabilis during experimental urinary tract infection, via four routes of immunization: subcutaneous, intranasal, transurethral, and oral. We assessed the efficacy of vaccination using the CBA mouse model of ascending urinary tract infection. Subcutaneous or intranasal immunization with formalin-killed bacteria and intranasal or transurethral immunization with purified MR/P fimbriae significantly protected CBA mice from ascending urinary tract infection by P. mirabilis (P < 0.05). To investigate the potential of MrpH, the MR/P fimbrial tip adhesin, as a vaccine, the mature MrpH peptide (residues 23 to 275, excluding the signal peptide), and the N-terminal receptor-binding domain of MrpH (residues 23 to 157) were overexpressed as C-terminal fusions to maltose-binding protein (MBP) and purified on amylose resins. Intranasal immunization of CBA mice with MBP-MrpH (residues 23 to 157) conferred effective protection against urinary tract infection by P. mirabilis (P < 0.002).

Adhesins, Bacterial↗

Interstitial cystitis.

Appropriate diagnostic tests for interstitial cystitis remain uncertain. One or more promising markers for this disease have been described which may provide a noninvasive means for diagnosis as well as clues to pathogenesis of this disease. Treatment remains empiric.

Bacterial Infections↗