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S J Jacobsen

Publications and source records attributed to S J Jacobsen.

At least 19 recordsLinked to original sources

Identification of an association between HLA class II alleles and low antibody levels after measles immunization.

This is the first large cohort study to report a genetic association between humoral antibody level after measles vaccine and the HLA class II genes. The WHO goal to eradicate measles world-wide magnifies the importance of data relating to the influence of immunogenetics on measles vaccine-induced antibody responses. We present here the analysis of 242 individuals who received one dose of measles-mumps-rubella-II (MMR-II) vaccine at the age of 15 months and were genotyped for HLA class II alleles. These subjects fit into one of three categories; 72 were classified as seronegative, 93 were seropositive and 77 were serohyperpositive. HLA-DRB1*03 (odds ratio (OR), 2.22) and HLA-DPA1*0201 (OR, 1.71) were significantly associated with measles vaccine seronegativity, while additional alleles provided suggestive evidence of association with seronegativity: DQA1*0201, DQB1*0201, and DQA1*0501. The alleles DRB1*03 and DQA1*0201 remained statistically significant after accounting for the effects of other alleles. These findings are crucial in designing both measles eradication by the use of vaccine, and future vaccines to be used in genetically heterozygous populations.

Alleles↗

Prostate volume and prostate-specific antigen in the absence of prostate cancer: a review of the relationship and prediction of long-term outcomes.

BACKGROUND: The risk for long-term outcomes associated with benign prostatic hyperplasia (BPH) has not been well characterized. Untreated, BPH can lead to complications and negative outcomes, such as deterioration of bladder function, urinary tract infection, acute urinary retention (AUR), and surgery. METHODS: A literature review was conducted to summarize the results of studies investigating the relationship of prostate volume and PSA with prediction of long-term outcomes in the absence of prostate cancer. RESULTS: In the studies reviewed, men with moderate to severe symptoms, depressed uroflow, prostatic enlargement and elevated PSA were at greater risk for developing subsequent AUR or surgery. Men with prostatic enlargement had a 3-fold higher risk for acute urinary retention and were 4 times more likely to have had any treatment for BPH. CONCLUSIONS: The results of these studies may assist physicians in discussing treatment options as well as long-term complications with patients.

Clinical Trials as Topic↗

Boy/girl differences in risk for reading disability: potential clues?

The authors conducted a case-control study to determine whether risk factors for reading disability (RD) differentially affect boys and girls. The study population included all children born between 1976 and 1982 in Olmsted County, Minnesota (n = 5,701). A total of 303 RD cases were identified by using intelligence quotient and achievement test scores collected from school and medical records. After excluding those who met exclusion criteria (n = 869), controls consisted of all children not identified with RD (n = 4,529). The authors examined the association between RD and potential risk factors in boys and girls and confirmed their results in multivariable logistic regression models. Multivariable models indicated that girls of low birth weight were more than twice as likely to be identified as RD (odds ratio (OR) = 2.94, 95% confidence interval (CI): 1.09, 6.25). Girls whose mothers had 12 or fewer years of education were twice as likely to be identified as RD (OR = 2.14, 95% CI: 1.24, 3.72). However, girls whose fathers were aged 35 years or older at the time of birth were less likely to be identified as RD (OR = 0.24, 95% CI: 0.06, 0.92). Only 12 or fewer years of paternal education was associated with increased RD in boys (OR = 2.28, 95% CI: 1.59, 3.27). Boys and girls appear to be differentially susceptible to RD risk factors, suggesting that the biologic processes leading to RD may differ between boys and girls.

Adolescent↗

Role of HPC2/ELAC2 in hereditary prostate cancer.

The HPC2/ELAC2 gene on chromosome 17p was recently identified as a candidate gene for hereditary prostate cancer (HPC). To confirm these findings, we screened 300 prostate cancer patients (2 affected members/family) from 150 families with HPC for potential germ-line mutations using conformation-sensitive gel electrophoresis, followed by direct sequence analysis. The minimum criteria for our families with HPC was the presence of 3 affected men with prostate cancer. A total of 23 variants were identified, including 13 intronic and 10 exonic changes. Of the 10 exonic changes, 1 truncating mutation was identified, a Glu216Stop nonsense mutation. This nonsense variant was found in 2 of 3 affected men in a single family. The remaining nine alterations included five missense, three silent, and one variant in the 3' untranslated region. To additionally test for potential associations of polymorphic variants and increased risk for disease, we genotyped two common polymorphisms, Ser217Leu and Ala541Thr, in 446 prostate cancer patients from 164 families with HPC and 502 population-based controls. The frequency of the Leu217 variant was similar for patients (32.3%) and controls (31.8%), as was the frequency of the Thr541 variant (5.4% among patients versus 5.2% among controls). In contrast to previous reports, we found no association of the joint effects of Leu271 and Thr541 (odds ratio, 1.04; 95% confidence interval, 0.57-1.89). Overall, our results did not reveal any association between these two common polymorphisms and the risk for HPC. The finding of a nonsense mutation in the HPC2/ELAC2 gene confirms its potential role in genetic susceptibility to prostate cancer. However, our data also suggest that germ-line mutations of the HPC2/ELAC2 are rare in HPC and that the variants Leu217 and Thr541 do not appear to influence the risk for HPC. Cumulatively, these results suggest that alterations within the HPC2/ELAC2 gene play a limited role in genetic susceptibility to HPC.

Adult↗

Outcomes for men with clinically nonmetastatic prostate carcinoma managed with radical prostactectomy, external beam radiotherapy, or expectant management: a retrospective analysis.

BACKGROUND: With a lack of data from randomized trials, the optimal management of men with nonmetastatic prostate carcinoma is controversial. The authors sought to define the outcomes of three common strategies for managing patients with nonmetastatic prostate carcinoma: expectant management, radiotherapy, and radical prostatectomy. METHODS: The authors conducted a retrospective cohort study with standardized collection of key prognostic data, including centralized assignment of Gleason grades from original biopsy specimens. Participants included all Connecticut hospitals (the expectant management cohort) and three academic medical centers in other states (the radiotherapy and surgery cohorts). Two thousand three hundred eleven consecutive men ages 55-74 years who were diagnosed during 1971-1984 with nonmetastatic prostate carcinoma and were treated at the participating sites were included. RESULTS: Kaplan-Meier estimates with 95% confidence intervals (95% CI) of overall survival at 10 years for each cohort were as follows: expectant management cohort, 42% of patients (95% CI, 38-46%); radiotherapy cohort, 52% of patients (95% CI, 46-58%); and radical prostatectomy cohort, 69% of patients (95% CI, 67-71%); for disease specific mortality, the estimates were as follows: expectant management cohort, 75% of patients (95% CI, 71-79%); radiotherapy cohort, 67% of patients (95% CI, 61-73%); and radical prostatectomy cohort, 86% of patients (95% CI, 84-88%). There were large differences in distributions of important prognostic factors among men in the different treatment groups. CONCLUSIONS: These data provide precise estimates of the outcomes of patients who have been treated with different modalities for nonmetastatic prostate carcinoma in the recent past. Direct comparisons of outcomes between treatment groups are inadvisable because of the different characteristics of patients who select these alternative management strategies.

Aged↗

Twin studies of immunogenicity--determining the genetic contribution to vaccine failure.

CONTEXT: Estimating the magnitude of the genetic contribution to the overall variation of antibody levels among individuals should help clarify the role of genetic association in the biological mechanism of vaccine response and failure. This, in turn, should help guide the design of improved vaccines with enhanced efficacy. OBJECTIVE: To explore the magnitude of genetic influence on antibody levels following measles, mumps and rubella vaccines. DESIGN: Cross-sectional survey study. SETTING: Olmsted County, Minnesota. PARTICIPANTS: Healthy twin-pairs. Of the 100 twin-pairs enrolled, 45 were monozygotic. INTERVENTIONS: Determinations of zygosity, vaccine status, and quantitative IgG to measles, mumps, and rubella. MAIN OUTCOME MEASURE: Heritability (ratio of genetic variance to total variance). RESULTS: The number of vaccine-doses, the age at initial immunization, and the time between immunization and sampling did not differ between monozygotic and dizygotic twin pairs. The genetic variance - the variance in antibody levels presumably due to genetic effects - was 0.49 for measles, 0.54 for mumps, and 0.13 for rubella. Heritability, the ratio of genetic variance to total variance, was 88.5% for measles, with the lower bound of a one-sided 95% confidence interval equal to 52.4%. The heritability was, for mumps, 38.8% with a lower bound of 1.60%. The heritability for rubella was 45.7% with a lower bound of 4.94%. CONCLUSION: Our data support the concept that genetic influences play a substantial role in the variation of antibody levels following immunization against measles and, to a lesser extent, mumps and rubella.

Adolescent↗

Correlations between measles, mumps, and rubella serum antibody levels in Olmsted County school children.

We examined correlations between serum antibody levels to determine whether individuals with low levels of antibody to one component of the measles, mumps, and rubella (MMR) vaccine were also likely to have low antibody levels to the other MMR vaccine components. Our results indicate that children who had a low antibody level to one component of the MMR vaccine had a modest probability of having a low antibody level to either of the other MMR vaccine components. Overall, we found small, but statistically significant, correlations between antibody levels that were largely unaffected by race, sex, age at immunization, and time since immunization. While the correlations we observed were modest, approximately 25% of our population was seronegative for at least one component of the MMR vaccine. Therefore, our results support the current policy of continuing to administer the trivalent MMR vaccine even when only a single low antibody titer is observed.

Adolescent↗

Time trends in the prevalence of atherosclerosis: a population-based autopsy study.

PURPOSE: Mortality from coronary heart disease is declining but little is known about trends in the prevalence of atherosclerosis. Autopsy rates in Olmsted County, Minnesota, are higher than the national average, offering an opportunity to address this matter. In this study, we determined the prevalence of anatomic coronary disease among autopsied Olmsted County residents and examined the generalizability of these findings. SUBJECTS AND METHODS: Reports of the 2,562 autopsies performed between 1979 and 1994 on Olmsted County residents > or =20 years of age were reviewed for the presence of coronary disease. RESULTS: Among autopsied decedents less than 60 years old at death and among coroner's cases, the prevalence of anatomic coronary disease declined with time (P for trend = 0.05); no trend was detected among older persons or noncoroner's cases. By logistic regression analysis, the crude odds ratio ([OR] per 5 years) for the association between time and anatomic coronary disease was 0.94 (95% confidence interval [CI]: 0.86 to 1.03; P = 0.18]. Age, sex, and antemortem diagnosis of heart disease were also strongly related to the presence of disease. After adjustment for sex and antemortem diagnosis of heart disease, the prevalence of anatomic coronary disease decreased more in younger people than in older people (age 40 years: OR 0.43 [95% CI: 0.24 to 0.80]; age 60 years: OR 0.62 [95% CI: 0.45 to 0.87]; age 80 years: OR 0.89 [95% CI: 0.64 to 1.23]). CONCLUSION: The prevalence of anatomic coronary disease at autopsy decreased between 1979 and 1994, particularly among younger people, supporting the notion that the burden of coronary disease has shifted toward the elderly. These results suggest that the decreased incidence of coronary artery disease has contributed to the recent decrease in coronary mortality, particularly among younger people.

Adult↗

Natural history of benign prostatic hyperplasia.

Studies in varied settings have provided estimates of the prevalence of surrogate markers of benign prostatic hyperplasia (BPH). In population-based studies, the prevalence of moderate-to-severe lower urinary tract symptoms and depressed peak urinary flow rates increases across successively older age groups. Prostatic volume follows a similar pattern. Unlike clinic-based studies in which correlations are almost nonexistent, the population-based studies demonstrate a modest correlation among lower urinary tract symptoms, peak urinary flow rates, and prostatic volume. These cross-sectional observations extend to serum prostate-specific antigen levels and postvoid residual urine volumes. Data collected during the longitudinal follow-up study of men participating in the Olmsted County Study of Urinary Symptoms and Health Status Among Men provide a more detailed description of the natural history of changes in these surrogate markers of BPH. They also provide insights into their relation with each other and with long-term outcomes of BPH, such as acute urinary retention and treatment of BPH. These data demonstrate the progressive nature of BPH and are useful for the design and interpretation of clinical trials. Furthermore, they suggest that observational studies of etiology and prognosis should take advantage of the spectrum of disease reflected by the full range of values of these quantitative traits, rather than an arbitrary dichotomized outcome.

Age Factors↗

Introduction.

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5-alpha Reductase Inhibitors↗

Referral to autopsy: effect of antemortem cardiovascular disease: a population-based study in Olmsted County, Minnesota.

PURPOSE: Autopsy studies can provide insight into disease trends and their determinants, including data on the prevalence of atherosclerosis. However, such studies are subject to autopsy bias, which limits their generalizability to the source population. The impact of this bias on autopsy based estimates of time trends in heart disease prevalence is unknown. To report on the trends over time in autopsy rates in Olmsted County, MN, to examine the association between clinical diagnoses of cardiovascular diseases (CVDs) and referral to autopsy and how this association may have changed over time. METHODS: We examined the trends in autopsy rates between 1979 and 1994 in Olmsted County, and the association between antemortem characteristics including cardiovascular diagnoses and autopsy referral. RESULTS: From 1979 to 1994, a total of 9110 residents died in Olmsted County. The average annual autopsy rate was 30%. Autopsy rates declined from 36% in 1979 to 23% in 1994, corresponding to an average decline of 0.6%/year (p < 0.01). Referral to autopsy was positively associated with younger age, male sex, in-hospital place of death, antemortem diagnoses of myocardial infarction (MI) or peripheral vascular disease (PVD), and earlier calendar period. There was no evidence of an interaction between calendar period and any of these predictor variables. Antemortem diagnosis of heart failure was associated with a decrease in the odds of referral to autopsy over time as compared to persons without such diagnosis. CONCLUSIONS: In Olmsted County, autopsy rates, although declining over time, have remained on average approximately 30%. Antemortem diagnoses of MI or PVD are associated with autopsy referral but this association did not change over time. While the greater decline overtime in the use of autopsy observed among decedents with an antemortem diagnosis of congestive heart failure (CHF) deserves further studies, the present findings reduce the concern for bias of time trends in the prevalence of atherosclerosis by changes in the clinical characteristics of decedents referred to autopsy.

Adult↗

Rehabilitation of the geriatric vascular amputee patient: a population-based study.

OBJECTIVES: To determine the rate of successful prosthetic fitting in geriatric vascular amputees in the community and to determine predictors of successful fit. DESIGN: Epidemiologic survey. SETTING: General community, Olmsted County, Minnesota. PATIENTS: All Olmsted County residents more than 65 years old who had a major lower extremity amputation (below knee amputation [BKA] or higher) for peripheral vascular disease between 1974-1995, of whom 199 were identified. Median age at amputation was 79.7 years with a median survival of 1.5 years. INTERVENTION: A retrospective chart review. MAIN OUTCOME MEASURE: Successful prosthetic fit. RESULTS: Amputation levels were: 64% BKA, 4.5% knee disarticulation, 31% above knee amputation (AKA), and 0.5% hip disarticulation. Only 36% of the population was successfully fitted, compared with 74% of patients referred to the Amputee Clinic. Major reasons for not being fitted included death, reamputation, cerebrovascular disease, and cognitive deficits. Increased age (p < .001), cerebrovascular disease (p < .001), dementia (p = .002), and AKA (p < .001) were associated with failure to fit. CONCLUSION: The high probability of successful prosthetic fitting reported among referral practices cannot be generalized to unselected elderly individuals. However, selected individuals can successfully be fitted with a prosthesis; knowledge of predictors of prosthetic fitting may facilitate setting of realistic goals during presurgical counseling in this age group.

Age Factors↗

Incidence of reading disability in a population-based birth cohort, 1976-1982, Rochester, Minn.

OBJECTIVE: To report the incidence of reading disability among school-aged children. SUBJECTS AND METHODS: In this population-based, retrospective birth cohort study, subjects included all 5718 children born between 1976 and 1982 who remained in Rochester, Minn, after the age of 5 years. Based on records from all public and nonpublic schools, medical facilities, and private tutorial services and on results of all individually administered IQ and achievement tests, extensive medical, educational, and socioeconomic information were abstracted. Reading disability was established with use of research criteria based on 4 formulas (2 regression-based discrepancy, 1 non-regression-based discrepancy, and 1 low achievement). RESULTS: Cumulative incidence rates of reading disability varied from 5.3% to 11.8% depending on the formula used. Boys were 2 to 3 times more likely to be affected than girls, regardless of the identification methods applied. CONCLUSIONS: In this population-based birth cohort, reading disability was common among school-aged children and significantly more frequent among boys than girls, regardless of definition.

Adolescent↗

Prostate-specific antigen levels in young white and black men 20 to 45 years old.

OBJECTIVES: To determine the prostate-specific antigen (PSA) levels and PSA change over time in young white and black men 20 to 45 years old. METHODS: The Department of Defense Serum Repository, a serum bank that stores all residual serum from the military human immunodeficiency virus screening program at -25 degrees C, was sampled to obtain a total of 588 black and 588 white subjects 20 to 45 years old. This was a retrospective study with only demographic data available on the studied subjects. The samples used for this study were collected between June 24, 1988 and June 12, 1996. Individuals with a history of prostate disease were excluded by query of a centralized Department of Defense diagnosis database. Three serum specimens evenly distributed over a mean of 6 years were selected for each individual to determine the free and total PSA levels and PSA velocity. The Hybritech Tandem-E PSA assay was used for the total PSA measurement, and the Hybritech Tandem-R assay was used for the free PSA measurement. RESULTS: The baseline serum PSA levels differed by race (P = 0.04). The median (25th, 75th percentile) baseline serum PSA levels for black men 20 to 29, 30 to 39, and 40 to 45 were 0.38 ng/mL (0.26, 0.61), 0.45 ng/mL (0.32, 0. 67), and 0.52 ng/mL (0.37, 0.73), respectively. The median baseline serum PSA levels for the same decade groups in white men were 0.38 ng/mL (0.27, 0.57), 0.45 ng/mL (0.28, 0.68), and 0.40 ng/mL (0.26, 0. 64), respectively. The PSA velocity was higher in white men than in black men (mean 2.8%/yr and 1.6%/yr, respectively, P = 0.032). CONCLUSIONS: These results suggest that although black men 20 to 45 years old have higher baseline serum PSA levels than white men of the same age, the PSA velocity is greater in young white than in young black men. Additional work is needed to determine the clinical significance of these findings.

Adult↗

Digital rectal examination and prostate-specific antigen abnormalities at the time of prostate biopsy and biopsy outcomes, 1980 to 1997.

OBJECTIVES: To assess the temporal trends in the prevalence of pre-biopsy abnormalities in digital rectal examination (DRE) findings, serum prostate-specific antigen (PSA) levels, and cancer detection rates by abnormality in all men from the community who had a prostate biopsy. METHODS: All Olmsted County, Minnesota residents who had their first prostate biopsy performed between January 1980 and December 1997 were identified (n = 1729). The complete medical records of these men were reviewed to determine the clinical findings at the time of the biopsy and the biopsy outcome. RESULTS: The prevalence of an abnormal DRE decreased from 69% in 1980 to 1986 to 45% in 1993 to 1997 (P <0.001). The prevalence of an isolated elevated PSA level (normal DRE) increased from 28% in 1987 to 1992 to 42% in 1993 to 1997 (P <0.001). In men diagnosed with cancer, 55% had an abnormal DRE in 1993 to 1997 (P <0.001). Prostate cancer was detected in 471 (37%) of 1280 men with an abnormal DRE or elevated PSA level noted within 6 weeks of the biopsy. The positive predictive value for prostate cancer was 61% (229 of 373) in men with an abnormal DRE and elevated PSA, 34% (166 of 494) in men with an elevated PSA only, and 18% (60 of 327) in men with an abnormal DRE only. CONCLUSIONS: The prevalence of an abnormal DRE at the time of biopsy has declined and that of an isolated elevated PSA has increased. However, nearly 40% of men with abnormalities in both PSA and DRE at the time of biopsy had a negative biopsy for prostate cancer. An increase in both the sensitivity and specificity of screening tests may further enhance the early detection of prostate cancer and potentially decrease the high negative biopsy rate.

Aged↗

Prognostic value of treadmill exercise testing in elderly persons.

BACKGROUND: Recent exercise testing guidelines recognized a gap in knowledge about the prognostic value of treadmill exercise testing in elderly persons. OBJECTIVE: To test the hypothesis that treadmill exercise testing has equal prognostic value among elderly (> or =65 years of age) and younger (<65 years of age) persons and to examine the incremental value of this testing over clinical data. DESIGN: Inception cohort with a median follow-up of 6 years. SETTING: Olmsted County, Minnesota. PATIENTS: All elderly (n = 514) and younger (n = 2593) residents of Olmsted County who underwent treadmill exercise testing between 1987 and 1989. MEASUREMENTS: Overall mortality and cardiac events (cardiac death, nonfatal myocardial infarction, and congestive heart failure). RESULTS: Compared with younger patients, elderly patients had more comorbid conditions, achieved a lower workload (6.0 and 10.7 metabolic equivalents; P < 0.001), and had a greater likelihood of a positive exercise electrocardiogram (28% and 9%; P < 0.001). With median follow-up of 6 years, overall survival (63% and 92%; P < 0.001) and cardiac event-free survival (66% and 95%; P < 0.001) were worse among elderly persons than among younger persons. Workload was the only treadmill exercise testing variable associated with all-cause mortality in both age groups, and the strength of association was similar. Workload and angina with exercise testing were associated with cardiac events in both age groups, whereas a positive exercise electrocardiogram was associated with cardiac events only in younger persons (P < 0.05 for all comparisons). After adjustment for clinical variables, workload was the only additional treadmill exercise testing variable that was predictive of death (P < 0.001) and cardiac events (P < 0.05); the strength of the association was similar in both age groups. Each 1-metabolic equivalent increase in exercise capacity was associated with a 14% and 18% reduction in cardiac events among younger and elderly persons, respectively. CONCLUSIONS: In elderly persons, treadmill exercise testing provided prognostic information that is incremental to clinical data. After adjustment for clinical factors, work-load was the only treadmill exercise testing variable that was strongly associated with outcome, and its prognostic effect was of the same magnitude in elderly and younger persons.

Age Factors↗

Sex differences in evaluation and outcome of unstable angina.

CONTEXT: The existence of sex bias in the delivery of cardiac care is controversial, and little is known about the association between sex and delivery of care and outcomes at an early point in the diagnostic sequence, such as when patients present for the evaluation of chest pain. OBJECTIVE: To test the hypothesis that female sex is negatively associated with care delivered to and outcomes of persons diagnosed as having unstable angina. DESIGN: Inception population-based cohort study with an average of 6 years of follow-up. SETTING: Emergency departments (EDs) in Olmsted County, Minnesota. PATIENTS: A total of 2271 Olmsted County residents (1306 men and 965 women) who presented to the ED for the first time with symptoms meeting criteria for unstable angina between 1985 and 1992. MAIN OUTCOME MEASURES: Use of cardiac procedures within 90 days of ED visit, overall mortality, and cardiac events (cardiac death, nonfatal myocardial infarction, nonfatal cardiac arrest, and congestive heart failure), compared by sex and Agency for Health Care Policy and Research cardiovascular risk category (low, intermediate, or high). RESULTS: Women were older (P<.001), more likely to have a history of hypertension (P = .001), and less likely to present with typical angina (P = .004) than men. Men were more likely than women to undergo noninvasive cardiac tests (relative risk [RR], 1.27; 95% confidence interval [CI], 1.14-1.40) as well as invasive cardiac procedures (RR, 1.72; 95% CI, 1.51-1.97). After adjustment, male sex was associated with a 24% increase in the use of cardiac procedures. Survival of both men and women in the high and intermediate risk categories was significantly lower than expected per the general population (P<.001). Women had a worse outcome than men, but after multivariate adjustment, male sex was associated with a trend toward an increase in the risk of death (RR, 1.23; 95% CI, 0.99-1.54) and significantly associated with increased risk of cardiac events (RR, 1.21; 95% CI, 1.03-1.42). CONCLUSIONS: Our population-based data indicate that after an ED visit for symptoms of unstable angina, the use of cardiac procedures was lower in women, but after taking into account baseline characteristics, men experienced worse outcomes.

Aged↗

Epidemiology of prostatitis.

Prostatitis is the third most important condition of the prostate. Problems in the diagnosis and classification of this condition, however, have hindered epidemiologic research. Consequently, our understanding of the incidence of prostatitis and factors that increase its probability is limited. Recent studies suggest that the prevalence of prostatitis is 5% to 9% among unselected men in the community. Based on estimates from national data, approximately 2 million men in the United States seek treatment for prostatitis each year. A number of recent studies suggest that genetic, behavioral, and environmental factors; age; inflammatory mediators; and oxidative stress may be risk factors for prostatitis. However, findings from most of these studies may at best be considered preliminary because of problems with small sample sizes or lack of generalizability. Nonetheless, these studies suggest hypotheses that should be tested in well-designed population-based studies.

Age Factors↗