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T D Tosteson

Publications and source records attributed to T D Tosteson.

At least 19 recordsLinked to original sources
PubMed1997

Maximum androgen blockade in advanced prostate cancer: a meta-analysis of published randomized controlled trials using nonsteroidal antiandrogens.

OBJECTIVES: To assess the survival benefit of maximum androgen blockade (MAB) using nonsteroidal antiandrogens (NSAAs) through meta-analysis of published randomized controlled trials (RCTs). METHODS: All RCTs comparing treatment with NSAA plus either luteinizing hormone-releasing hormone (LHRH) or orchiectomy versus treatment with LHRH or orchiectomy alone were included if the necessary statistical summaries were present in the publication. Estimates and standard errors of log hazard ratio for overall survival and progression-free survival were derived from published studies using two methods: (1) reconstructing an annual life table from graphical presentations of survival distributions and fitting discrete proportional hazard models, and (2) reconstructing the log hazard ratio from reported P values and numbers of deaths. An alternative set of log hazard ratios was derived from figures presented in a summary report by the Prostate Cancer Trialists' Collaborative Group (PCTCG). Comparative meta-analyses were performed using the random effects approach of DerSimonian and Laird. Additionally, published studies were used in a random-effects-based meta-analysis of objective tumor response. RESULTS: Nine studies provided enough information to perform a meta-analysis for survival using one of the two methods. Estimates of relative risks (RR) comparing treatment with NSAA plus either LHRH or orchiectomy versus treatment with LHRH or orchiectomy alone with respect to overall survival were 0.78 (95% confidence intervals [CIs] 0.67 to 0.90) using method 1, and 0.84 (95% CI 0.76 to 0.93) using method 2. Sensitivity analyses based on PCTCG data showed that a favorable survival result for MAB was associated with NSAAs but not with steroidal antiandrogens and depended on randomization blinding and overall trial quality. Additionally, random-effects-based meta-analysis of published studies showed a significant increase in time-to-progression (RR = 0.74; 95% CI 0.63 to 0.86) and an increase in objective tumor responses for MAB using NSAAs compared with castration alone (odds ratio = 0.65; 95% CI 0.51 to 0.81; P = 0.00022). CONCLUSIONS: Inconsistent results have been published about the benefit of MAB in advanced prostate cancer. This meta-analysis supports a beneficial effect for MAB using NSAAs compared with castration alone, and sensitivity analyses suggest that the design of future trials should carefully address issues of patient characterization, randomization blinding, and other study quality issues.

Androgen Antagonists↗
PubMed1997

Racial differences in sleep-disordered breathing in African-Americans and Caucasians.

In this case-control family study of sleep-disordered breathing (SDB), we describe the distributions of SDB and SDB risk factors in African-Americans and Caucasians. A total of 225 African-Americans and 622 Caucasians, ages 2 to 86 yr, recruited as members of families with an individual with known sleep apnea (85 index families) or as members of neighborhood control families (63 families) were studied with an overnight home sleep-study, questionnaires, and physical measurements. A subsample underwent cephalometry. Outcome measures were the respiratory disturbance index (RDI) and a binary variable indicating the presence of increased apneic activity (IAA). In both races, a strong relationship was demonstrated between the (log transformed) RDI and age and age2. African-Americans with SDB were younger than Caucasians with SDB (37.2 +/- 19.5 versus 45.6 +/- 18.7 yr, p < 0.01). In subjects < or = 25 yr, RDI level and IAA prevalence were higher in African-Americans (odds ratio, adjusted for obesity, sex, proband sampling, and familial clustering, 1.88, 1.03 to 3.52, 95% CI). In this age group, racial differences also were observed in the relationship between RDI and age (p < 0.001 for the RDI-age interaction). This suggests that young African-Americans may be at increased risk for sleep apnea.

Adolescent↗
PubMed1996

The lack of association of marijuana and other recreational drugs with progression to AIDS in the San Francisco Men's Health Study.

We evaluated the associations of specific recreational drugs and alcohol with laboratory predictors of AIDS at entry into the San Francisco Men's Health Study (SFMHS) in 1984 and with the development of the acquired immunodeficiency syndrome (AIDS) during 6 years of follow-up. Marijuana use was associated with a decreased rate of progression to AIDS in the univariate analysis (RR = 0.7; P = 0.01). Marijuana use was more common among individuals with elevated HIV viral core protein antibody (p24Ab) titer (> 1:16) at baseline (P = 0.03); this finding suggests that marijuana users were healthier at baseline. When the data were adjusted for p24 Ab and other laboratory parameters, no association with progression to AIDS was observed for marijuana, suggesting that the observed univariate result was due to a difference in HIV-related disease at the time of enrollment. No statistically significant associations were observed for nitrites, methylene dioxyamphetamines, ethyl chloride, downers, cocaine, stimulants, narcotics, or psychedelic drugs. These data suggest no substantial association between use of these drugs and the development of AIDS among HIV-infected men.

Acquired Immunodeficiency Syndrome↗
PubMed1996

The accuracy of skin self-examination for atypical nevi.

We conducted a validation study to assess laypersons' ability to self-report atypical nevi. Study subjects were drawn from a large population-based cohort of middle-aged Swedish women who had responded to a previous health survey. The health survey questionnaire included color photographs of atypical nevi. Respondents were asked to examine their lower extremities for similar lesions. We invited 500 survey respondents to participate in a physician-conducted skin examination; 400 (80%) subjects agreed. We compared the results of skin self-examination for atypical nevi to the results of the physician-conducted skin examination. Using methods developed for this study, we estimated sensitivity as 29% and specificity as 85%. Positive predictive value was 20%; negative predictive value was 90%. We estimated that 12% of Swedish women have atypical nevi on the lower extremities. Although these findings suggest poor accuracy of skin self-examination for atypical nevi, our results may have been adversely affected by limiting self-examination to the legs and by the severity of atypical nevi shown in the comparison photographs used by survey respondents.

Adult↗
PubMed1996

Reliability of whole crypt mitotic count as a measure of cellular proliferation in rectal biopsies.

We conducted a reliability study of whole crypt mitotic count, a measure of cellular proliferation with potential use as an intermediate marker in studies of colorectal cancer risk and prevention. The study involved biopsies taken from two distinct locations at 8-10 cm from the anal verge for 20 subjects scheduled to undergo routine endoscopy. In addition to the overall count of mitoses per crypt (mitotic count), we investigated two novel measures based on the percentages of heights of mitotic cells within crypts: the mean height, and the maximum minus minimum (max - min) height of mitoses. The max - min height was positively correlated with mitotic count (r = 0.64); however, there was little correlation between mitotic count and the mean height of mitotic cells (r = 0.12). Components of variance were estimated for the three measures; for mitotic count and max - min height, the variability between persons was substantially greater than that between locations within an individual. For mean height, the between-person and between-location variabilities were roughly equal. These results suggest that whole crypt mitotic count has promise as a reliable measure of rectal cellular proliferation, but further studies will be necessary to assess the utility of this assay.

Adult↗
PubMed1995

The pathogenic role of Staphylococcus epidermidis capsular polysaccharide/adhesin in a low-inoculum rabbit model of prosthetic valve endocarditis.

BACKGROUND: The capsular polysaccharide/adhesin (PS/A) antigen of Staphylococcus epidermidis was required to produce endocarditis in a rabbit model in which infection resulted from hematogenous spread of bacteria from a contaminated catheter in the jugular vein. However, many prosthetic valve endocarditis (PVE) infections probably result from direct contamination of the valve with small numbers of bacteria during surgery. The role of PS/A in this situation was evaluated by modifying a rabbit model of endocarditis to partially mimic PVE. METHODS AND RESULTS: A Teflon catheter was contaminated with graded inocula of either PS/A-positive S epidermidis strain M187sp11 or the PS/A-negative, isogenic strain M187sn3 and inserted into the left ventricle through the aortic valve. The PS/A-positive strain had a 50% infectious dose of 1.1 x 10(2) cfu (95% CI, 3.3 to 3.7 x 10(3)) compared with 8.5 x 10(4) cfu of the PS/A-negative strain (95% CI, 8.6 x 10(3) to 8.5 x 10(5)). The odds for developing endocarditis were estimated to be 42 times higher for any given inoculum level of the PS/A-positive strain (P = .1). When the PS/A-positive strain was adherent to a catheter surface it survived in rabbit blood, whereas under the same conditions the PS/A-negative strain was killed approximately 90% in 1 hour. CONCLUSIONS: Direct contamination of an intraventricular foreign body by low levels of PS/A-positive S epidermidis results in endocarditis in rabbits, but at suitably high doses PS/A-negative strains have sufficient virulence to infect cardiac vegetations. PS/A enhances but is not absolutely required for bacterial virulence in a rabbit model of PVE.

Animals↗
PubMed1995

Calcium supplementation and rectal mucosal proliferation: a randomized controlled trial.

BACKGROUND: Data from studies using rodents suggest that dietary calcium inhibits bile acid-induced mucosal damage and experimental carcinogenesis in the large bowel. However, in humans, the effect of dietary calcium and calcium supplementation on proliferation and carcinogenesis in the large bowel has been unclear. PURPOSE: To assess the effect of calcium supplementation on rectal mucosal proliferation in humans, we conducted a multicenter, randomized, placebo-controlled, double-blinded trial. METHODS: Participants were part of a larger multicenter chemoprevention trial; all were at high risk for large-bowel neoplasia, with at least one large-bowel adenoma removed endoscopically within the 3 months before study entry but with no known polyps remaining. Subjects were randomly assigned to receive daily either 3000 mg of calcium carbonate (providing 1200 mg elemental calcium) or an identical-appearing placebo tablet. During a scheduled endoscopy 6-9 months after random assignment (approximately 1 year after the qualifying endoscopy), rectal mucosal samples were obtained from 333 patients (173 assigned to calcium and 160 assigned to placebo). Proliferating cell nuclear antigen (PCNA) labeling indices (LIs) were computed as the measure of proliferation in specimens from 146 patients receiving calcium and 129 patients receiving placebo. Bromodeoxyuridine (BrdU) labeling was used to measure proliferation in a smaller number of specimens (27 calcium-receiving and 31 placebo-receiving participants). For each scorable crypt having at least one labeled cell (or surrounded by crypts with at least one labeled cell), a crypt LI was calculated as the number of labeled cells divided by the total number of crypt cells. Crypt LIs were averaged to produce a participant's average LI. RESULTS: The overall unadjusted mean PCNA LIs (+/- SE) were similar in the calcium and placebo groups (3.85% +/- 0.08% versus 3.92% +/- 0.08%, respectively, P = .30). The overall unadjusted mean BrdU LIs (+/- SE) were 3.88% +/- 0.30% in the calcium group and 3.54% +/- 0.21% in the placebo group (P = .54). PCNA labeling indices in the most luminal 40% of the crypt were small but, if anything, were higher in the calcium group. There was no patient subgroup within which calcium had an antiproliferative effect; the overall findings persisted among patients with high and low calcium intake, high and low fat intake, and high and low fiber intake. CONCLUSIONS: Calcium supplementation does not decrease rectal mucosal proliferation, as measured by PCNA (and BrdU) immunohistochemistry, in patients with previous large-bowel adenomas. This study, therefore, does not provide evidence for an anticarcinogenic effect of calcium.

Adenoma↗
PubMed1995

Potentiation of Staphylococcus epidermidis catheter-related bacteremia by lipid infusions.

Lipid infusions given to low-birth-weight neonates are associated with coagulase-negative staphylococcal bacteremia. A rabbit model of catheter-related Staphylococcus epidermidis bacteremia was used to compare infection rates between animals receiving 20% lipid infusions with those receiving 10% glucose infusions. Bacterial growth was detected in 43 (66%) of 65 blood cultures obtained during lipid infusions but only 6 (7%) of 91 blood cultures obtained during glucose infusions (P < .001). S. epidermidis was cultured from 7 of 9 catheters recovered from lipid-infused rabbits but from only 3 of 13 catheters from glucose-infused rabbits (P = .016). Lipid but not glucose solutions containing low levels of protein (0.1%-1.0%) supported the survival and growth of S. epidermidis. These results suggest that lipids contribute to the survival and growth of S. epidermidis on contaminated catheters, enhancing the potential of these organisms to disseminate and cause bacteremia.

Animals↗
PubMed1995

The familial aggregation of obstructive sleep apnea.

An inherited basis for sleep-disordered breathing (SDB) has been suggested by reports of families with multiple affected members and by a previous study of the familial aggregation of symptoms of SDB. In this study, we quantify and characterize the aggregation of SDB and assess the degree to which familial similarities may be independent of obesity. This was a genetic-epidemiologic study that assessed the distribution of SDB in families identified through a proband with diagnosed sleep apnea and among families in the same community with no relative with known sleep apnea. SDB was assessed with overnight in-home monitoring of airflow, oxygen saturation, chest wall impedance, heart rate, and body movement. Standardized questionnaires were used to assess symptoms, and weight, height, and neck circumference were measured directly. Intergenerational and intragenerational correlation coefficients and pairwise odds ratios (ORs) were calculated with adjustment for proband sampling. In toto, 561 members of 91 families were studied: (1) 47 subjects with laboratory-confirmed SDB (index probands), (2) 44 community control subjects, and (3) the spouses and relatives of 1 and 2. Of all 91 families, 32 (35%) had two or more members with SDB, 30 (33%) had one affected member, and 29 had no affected members. SDB was more prevalent in the relatives of index probands (21%) than among neighborhood control subjects (12%) (p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

A clinical trial of antioxidant vitamins to prevent colorectal adenoma. Polyp Prevention Study Group.

BACKGROUND: People who consume a diet high in vegetables and fruits have a lower risk of cancer of the large bowel. Antioxidant vitamins, which are present in vegetables and fruits, have been associated with a diminished risk of cancers at various anatomical sites. We conducted a randomized, controlled clinical trial to test the efficacy of beta carotene and vitamins C and E in preventing colorectal adenoma, a precursor of invasive cancer. METHODS: We randomly assigned 864 patients, using a two-by-two factorial design, to four treatment groups, which received placebo; beta carotene (25 mg daily); vitamin C (1 g daily) and vitamin E (400 mg daily); or the beta carotene plus vitamins C and E. In order to identify new adenomas, we performed complete colonoscopic examinations in the patients one year and four years after they entered the study. The primary end points for analyses were new adenomas identified after the first of these two follow-up examinations. RESULTS: Patients adhered well to the prescribed regimen, and 751 completed the four-year clinical trial. There was no evidence that either beta carotene or vitamins C and E reduced the incidence of adenomas; the relative risk for beta carotene was 1.01 (95 percent confidence interval, 0.85 to 1.20); for vitamins C and E, it was 1.08 (95 percent confidence interval, 0.91 to 1.29). Neither treatment appeared to be effective in any subgroup of patients or in the prevention of any subtype of polyp defined by size or location. CONCLUSIONS: The lack of efficacy of these vitamins argues against the use of supplemental beta carotene and vitamins C and E to prevent colorectal cancer. Although our data do not prove definitively that these antioxidants have no anticancer effect, other dietary factors may make more important contributions to the reduction in the risk of cancer associated with a diet high in vegetables and fruits.

Adenomatous Polyps↗
PubMed1994

Transposon mutants of Staphylococcus epidermidis deficient in elaboration of capsular polysaccharide/adhesin and slime are avirulent in a rabbit model of endocarditis.

Virulence comparisons were made in a rabbit model of endocarditis between wild-type and transposon mutants of Staphylococcus epidermidis deficient in elaboration of the capsular polysaccharide/adhesin (PS/A) and slime. The parental phenotype grew from 36 (61%) of 59 cultures of blood. The PS/A-negative phenotype grew in 1 (1%) of 98 cultures of blood (P < .001). No animals infected with PS/A-negative strains developed endocarditis compared with 75% of rabbits infected with PS/A-positive strains. PS/A-producing strains survived better than did PS/A-deficient strains in intact, absorbed rabbit or human serum plus human leukocytes. There was also greater deposition of C3 onto the PS/A-deficient strains than with the PS/A-producing isogenic strains. PS/A functions as an antiphagocytic bacterial capsule preventing C3 deposition and phagocytosis; loss of this structure increases the strain's susceptibility to opsonic killing and decreases its virulence.

Analysis of Variance↗
PubMed1994

A two-stage validation study for determining sensitivity and specificity.

A two-stage procedure for estimating sensitivity and specificity is described. The procedure is developed in the context of a validation study for self-reported atypical nevi, a potentially useful measure in the study of risk factors for malignant melanoma. The first stage consists of a sample of N individuals classified only by the test measure. The second stage is a subsample of size m, stratified according the information collected in the first stage, in which the presence of atypical nevi is determined by clinical examination. Using missing data methods for contingency tables, maximum likelihood estimators for the joint distribution of the test measure and the "gold standard" clinical evaluation are presented, along with efficient estimators for the sensitivity and specificity. Asymptotic coefficients of variation are computed to compare alternative sampling strategies for the second stage.

Adult↗
PubMed1994

Clinical and roentgenographic results of decompression for lumbar spinal stenosis.

We reviewed 118 patients who underwent lumbar decompression without fusion for acquired lumbar spinal stenosis between 1980 and 1991. Fifty of these patients (15 men, 35 women) were clinically and roentgenographically reexamined, with quantification of postoperative degenerative changes. The presence of preoperative spondylolisthesis and a postoperative change in spondylolisthesis portended poor outcome. Men had better mean surgical outcome scores than did women, and 6% of the men and 28% of the women underwent further surgery for recurrent stenosis or instability. Women had larger mean postoperative changes in spondylolisthesis than did men. Patients with mild preoperative spondylolisthesis developed a larger slip after the procedure than did those with no preoperative slip. Women and patients with preoperative spondylolisthesis may require changes in existing treatment modalities to improve outcome or alterations in long-term expectations after lumbar decompression for stenosis.

Aged↗
PubMed1994

Durability of improved physician early detection of cancer after conclusion of intervention support.

Physicians can potentially play an important role in the early detection of cancer. Interventions designed to encourage these activities have been shown to improve physician performance for up to 1 year. To assess their real value, improved physician performance must be judged over the longer term. The Cancer Prevention in Community Practice Project assisted a random subset of practices in implementing cancer early detection office systems. One year later, these practices were found to have provided more indicated breast and colorectal cancer early detection services than practices that did not receive assistance. This report addresses whether 12-month improvements in breast and colorectal cancer early detection were durable at 24 months despite no appreciable ongoing project support. A cross-sectional survey of 20-30 established patients/practice was conducted 24 months after the introduction of the intervention. These results were compared with base-line, 6-, and 12-month cross-sectional surveys to determine whether increases in indicated services and recommendations persisted. A longitudinal model for binomial data was used to quantitatively assess durability of effects. Ninety-nine practices participated, and 81 provided data at all 4 evaluation intervals. In office systems practices, improvements in stool occult blood testing and self breast examination recommendations to patients were maintained between 12 and 24 months while improvements in mammography recommendations and clinical breast examinations declined somewhat but remained superior to performance in control practices. Some improvements in physician early detection of cancer performance were maintained between 12 and 24 months. Future studies of physician behavior change should include follow-up beyond 12 months.

Breast Neoplasms↗
PubMed1994

A prospective study of the association of serum neopterin, beta 2-microglobulin, and hepatitis B surface antigenemia with death in infants and children with HIV-1 disease.

A high percentage of HIV-1-infected infants and children in Romania are coinfected with hepatitis B virus. Little information is available on the impact of concurrent hepatitis B infection on the course of HIV-1 infection. We conducted a prospective cohort study over 1 year in a group of 68 HIV-1-infected infants and children to determine whether hepatitis B surface antigenemia, neopterin, and beta 2-microglobulin (B2M) predicted death. Among the 44 hepatitis B surface antigen-positive (HBsAg+) subjects at enrollment, 13 (30%) died during 1 year of follow-up. In comparison, two of 24 (8%) HBsAg-negative subjects died (RR = 7.7; p = 0.05). Higher initial serum concentrations of neopterin and B2M were negatively associated with survival. After stratifying by baseline clinical evidence of HIV-related disease, survival was negatively associated with HBsAg+ status (p = 0.04) in 33 children in stage P-2, adjusting for age, serum neopterin, and serum B2M levels. The results of this study suggest that serum neopterin is a marker for severity of clinical illness and that HBsAg+ status increases the mortality rate among children with clinical evidence of HIV infection.

Biopterins↗
PubMed1993

A retrospective cohort study of vasectomy and prostate cancer in US men.

OBJECTIVE: To examine the relationship between vasectomy and prostate cancer. DESIGN: Retrospective cohort study. SETTING: Husbands of nurses in 11 large states in the United States. PARTICIPANTS: In questionnaires administered in 1976 and 1978, 14,607 married female participants of the Nurses' Health Study reported vasectomy as the couple's form of contraception. In 1989, we contacted these 14,607 women and 14,607 age-matched participants whose husbands had not had a vasectomy prior to 1978 to ascertain their husband's disease status between 1976 and 1989. MAIN OUTCOME MEASURE: Diagnosis of prostate cancer. RESULTS: During the study period, from 1976 through 1989, 96 new cases of prostate cancer were diagnosed in the cohort. Vasectomy was associated with an increased risk of prostate cancer (age-adjusted relative risk, 1.56; 95% confidence interval, 1.03 to 2.37; P = .04). The relative risk of prostate cancer increased over time since vasectomy. Among men who had their vasectomy 20 or more years in the past, the relative risk of prostate cancer was 1.89 (95% confidence interval, 1.14 to 3.14; P = .005), and after excluding stage A and B cases, the relative risk was 2.06 (95% confidence interval, 0.95 to 4.43; P = .07). This elevated risk of prostate cancer among vasectomized men persisted when we adjusted for smoking, alcohol consumption, educational level, body mass index, and geographical area of residence. CONCLUSIONS: These results support evidence from other epidemiologic studies that vasectomy increases risk of prostate cancer. A biological mechanism whereby vasectomy influences the rate of prostate cancer may be related to a diminished secretory rate of prostatic fluid following vasectomy, or, alternatively, to the postvasectomy immune response to sperm antigens, which may cross-react with tumor-associated antigens and suppress tumor immunosurveillance mechanisms.

Adult↗