Incidence of physician-diagnosed interstitial cystitis in Olmsted County: a community-based study.

OBJECTIVE: To obtain community-based information about the incidence of interstitial cystitis, a chronic disabling condition of the bladder where knowledge is limited because there are no definitive diagnostic criteria. PATIENTS AND METHODS: All residents of Olmsted County, MN, USA who had received a physician-assigned diagnosis of interstitial cystitis between 1976 and 1996 were identified through the resources of the Rochester Epidemiology Project. The clinical findings at diagnosis and during the follow-up were ascertained from the community medical records for each study subject. RESULTS: In all, 16 women and four men received a diagnosis of interstitial cystitis during the study period. The overall age- and sex-adjusted (95% confidence interval) incidence rate was 1.1 (0.6-1.5) per 100 000 population. The age-adjusted incidence rates were 1.6 per 100 000 in women and 0.6 per 100 000 in men (P = 0.04). The median (range) age at initial diagnosis was 44.5 (27-76) years in women and 71.5 (23-79) years in men (P = 0.26). The median number of episodes of care-seeking for symptoms before the diagnosis was one for women and 4.5 for men (P = 0.03). The median duration from the onset of symptoms until the first diagnosis was 0.06 and 2.2 years in women and men, respectively (P = 0.2). CONCLUSIONS: These findings suggest that the incidence of interstitial cystitis in the community is extremely low. Although the gender difference may be real, the trend toward a later diagnosis in men than in women suggests a potential for missed diagnosis in men. This might explain some of the gender difference in the incidence of interstitial cystitis in men and women.

Cytochrome b562 variants: a library for examining redox potential evolution.

A general understanding of how cytochromes evolve within a fixed structure to optimize redox potential for specific bioenergetic processes does not exist. Toward this end, a library approach is used to investigate the range and distribution of redox potential which occurs when all sequence space available through mutation at two positions is examined within a fixed structural motif. Random mutation of Phe61 and Phe65 of cytochrome b562 (E. coli), and subsequent examination of a statistically significant sampling of this library, demonstrates that the redox potential can vary over 100 mV (>25% of the known accessible potential in native proteins with axial His-Met ligation) through mutation at these two positions. The redox potential of the wild-type protein occurs at an extremum of the distribution observed, indicating that Phe61 and Phe65 were most likely naturally selected to differentially stabilize the reduced state of the protein. At the other extremum, a compositionally conservative set of mutations (F61I, F65Y) leads to a 100 mV shift in the redox equilibrium toward the oxidized state. NMR analyses indicate that a charge-dipole interaction which results from mutation of phenylalanine to tyrosine at position 65 may be responsible.