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Biomedical subjects

B McKnight

Publications and source records attributed to B McKnight.

At least 55 records · Page 3Linked to original sources
PubMed1995

Population-based study of tamoxifen therapy and subsequent ovarian, endometrial, and breast cancers.

BACKGROUND: The success of tamoxifen in reducing the occurrence of contralateral breast cancer among breast cancer patients in clinical trials has prompted the study of its use in the primary prevention of breast cancer. Long-term risks associated with tamoxifen therapy, however, are still being evaluated, particularly with respect to subsequent cancer occurrence at sites other than the breast. PURPOSE: This population-based, nested case-control study investigated the risks of second primary cancers of the ovary, endometrium, and contralateral breast among women receiving tamoxifen for breast cancer in conventional medical practice. METHODS: A cohort of women diagnosed with breast cancer during 1978 through 1990 was identified from a population-based cancer registry. Case subjects included all women in the cohort who subsequently developed second primary ovarian (n = 39), endometrial (n = 42), or contralateral breast (n = 234) cancer prior to 1992. Control subjects were a random sample of the cohort who did not develop a second primary malignancy; they were matched to the case subjects on age, disease stage, and year of initial breast cancer diagnosis (approximately two control subjects per case subject). Information on tamoxifen use as well as on potential risk factors for the second primary cancers was obtained through medical record abstractions and physician questionnaires. RESULTS: The percentage of women who had received tamoxifen was 18% and 20%, respectively, among ovarian cancer case subjects and control subjects; 26% and 31%, respectively, among endometrial cancer case subjects and control subjects; and 10% and 18%, respectively, among contralateral breast cancer case subjects and control subjects. The mean duration of tamoxifen use was less than 2 years for all groups. The relative risks for ovarian and endometrial cancers in women who took tamoxifen were relatively low but were consistent with no association (for ovarian cancer, matched odds ratio [mOR] = 0.6 and 95% confidence interval [CI] = 0.2-1.8; for endometrial cancer, mOR = 0.6 and 95% CI = 0.2-1.9). Tamoxifen therapy was associated with a decreased risk of contralateral breast cancer (mOR = 0.5; 95% CI = 0.3-0.9), especially if the drug had been taken for more than 1 year (mOR = 0.4; 95% CI = 0.2-0.9) or if the women were postmenopausal at initial breast cancer diagnosis (mOR = 0.4; 95% CI = 0.2-0.8). CONCLUSIONS AND IMPLICATIONS: These data suggest that short durations of tamoxifen therapy are not associated with an increased risk of endometrial or ovarian cancer but are associated with a reduction in contralateral breast cancer risk. It would not be appropriate, however, to generalize these results to women who receive tamoxifen for longer periods.

Adult↗
PubMed1995

Use of human papillomavirus type 6 capsids to detect antibodies in people with genital warts.

Human papillomavirus (HPV) type 6 capsids were produced by recombinant vaccinia viruses and used in a capture ELISA to screen 901 human sera from three studies of genital HPVs. The highest seroprevalence was observed among subjects with recurrent genital warts. In a population-based case-control study of genital warts, 26 (58%) of 45 women with recurrent genital warts were seropositive compared with 19 (19%) of 101 control women with no history of genital warts (odds ratio, 6.5; 95% confidence interval, 3.0, 14.1). Among a cohort of pregnant women, 7 (88%) of 8 with recurrent warts were seropositive compared with 24 (30%) of 79 pregnant women with no such history. A significant association between seropositivity to HPV-6 capsids and the detection of HPV-6/11 DNA from genital specimens by polymerase chain reaction was also observed. Men with genital warts were less likely to be seropositive than were women with genital warts, and a positive association between the number of sex partners and seropositivity was observed among only the female university students.

Adult↗
PubMed1995

A case-control study to evaluate efficacy of screening for faecal occult blood.

OBJECTIVES: Faecal occult blood testing is routinely used for early detection of colorectal cancer, but evidence of its efficacy in preventing death from colorectal cancer is limited. A case-control study was carried out to evaluate whether screening for faecal occult blood is associated with a reduced risk of fatal colorectal cancer. SETTING: A health maintenance organisation in western Washington State, which has offered its members faecal occult blood testing every two years since 1983. METHODS: Cases (n = 248) were members of the health maintenance organisation who died from colorectal cancer between 1986 and 1991. For each case, two control subjects, who did not die from colorectal cancer and who were similar to each case in age, gender, and year of enrollment at the health maintenance organisation, were randomly selected from the membership list of the year in which the case was diagnosed (n = 496). Information about episodes of faecal occult blood testing (including the location and reason for the test, and the evaluation of positive tests) and potential confounders was obtained from medical records. RESULTS: Cases were less likely than controls to have ever been screened (odds ratio (OR) = 0.7, 95% confidence interval (CI) 0.5 to 1.0), consistent with a beneficial impact of screening. There was little difference, however, for screening that had taken place within a three year period before diagnosis (OR = 0.9, 95% CI 0.6 to 1.2), the maximum interval during which most tumours ought to have been detectable by faecal occult blood testing. A reduction in risk was seen for home testing but not for office testing, and in individuals aged less than 75 but not in those aged 75 or older. Although most of the 21 controls with a positive faecal occult blood test underwent some additional testing, only five (24%) were evaluated with colonoscopy or air contrast barium enema. CONCLUSIONS: While there can be uncertainty as to whether specific faecal occult blood tests were performed as screening or diagnostic tests, those performed at home and in younger persons may be relatively less likely to be diagnostic tests that were misclassified as screening. Thus the modest reduced risk associated with faecal occult blood testing in these settings/persons may reflect genuine benefit. However, the presence of a reduced risk associated with a screening faecal occult blood test received in the past, well before a tumour or polyp might bleed enough to allow detection, is compatible with uncontrolled confounding. Interpretation is further complicated by the fact that a number of individuals in the study group who had positive test results underwent limited or no diagnostic testing. Thus our results should be interpreted with considerable caution.

Age Factors↗
PubMed1995

Colorectal cancer in patients with esophageal adenocarcinoma.

The incidence of adenocarcinoma of the esophagus and gastric cardia has been rising rapidly in Western Europe and the United States, especially among white males. Previous reports, based on case series, have suggested an association between colonic neoplasia and Barrett's esophagus, a metaplastic condition of the lower esophagus that can lead to adenocarcinoma. We analyzed cancer incidence data from 1973 to 1989 from the nine population-based registries of the Surveillance, Epidemiology, and End Results program of the United States National Cancer Institute to investigate this association, using malignancies as an outcome. Using a case-control design, we measured the odds of being diagnosed with colorectal adenocarcinoma some time in life among persons diagnosed with adenocarcinomas of the esophagus or gastric cardia relative to persons diagnosed with squamous cell carcinomas of the esophagus. Among white males the odds ratio was 1.44 (95% confidence interval, 1.03-2.02). This association appeared to be independent of which cancer occurred first. In contrast, white females with adenocarcinomas were less likely to be diagnosed with colorectal cancer than those with squamous cell carcinomas (odds ratio, 0.39; 95% confidence interval, 0.19-0.78). These associations appeared to be specific for colorectal tissue because there was no relationship between histological type of esophageal cancer and prostate cancer in men or breast cancer in women. We conclude that men with esophageal adenocarcinoma may be more likely to be diagnosed with colorectal cancer in their lifetime than expected; the opposite association may exist for women.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1994

Risk of breast cancer in relation to the interval since last full term pregnancy.

OBJECTIVE: To examine whether the risk of breast cancer is increased by a recent term pregnancy. DESIGN: Population based case-control study. SETTING: Eight areas in the United States. SUBJECTS: Cases were 2279 multiparous women residents of the eight areas aged 25-49 who were diagnosed as having breast cancer during 1980-2. Controls were 2357 multiparous women selected from the same areas by random digit dialing. MAIN OUTCOME MEASURE: Relative risk of developing breast cancer according to the time interval since last full term pregnancy. RESULTS: The distribution of intervals since the last term pregnancy was similar in cases and controls. Adjusted for age, parity, and age at first term pregnancy, the odds ratios observed for categories of years since the last full term pregnancy were: 0-2 years, odds ratio 1.16 (95% confidence interval 0.84 to 1.59); 3-6 years, odds ratio 1.21 (0.95 to 1.54); 7-9 years, odds ratio 1.04 (0.84 to 1.38); > or = 10 years, odds ratio 1.00 (reference). CONCLUSIONS: Among multiparous women aged 25-49 years there was no association between the risk of breast cancer and the time interval since the last full term pregnancy.

Adult↗
PubMed1994

Cigarette smoking and functional ovarian cysts.

This population-based case-control study assessed the effect of current cigarette smoking on the risk of functional ovarian cyst development. Cases were all 15-39 year-old enrollees of Group Health Cooperative of Puget Sound (GHC) who had either an inpatient primary diagnosis of functional ovarian cyst in 1988 or 1989 (n = 61) or an outpatient primary diagnosis of functional ovarian cyst at five GHC primary care clinics (n = 37). Controls were randomly selected enrollees matched to cases on age, primary care clinic, and enrollment date (n = 239). A total of 36.7% of cases and 20.5% of controls were determined by medical record review to be current smokers. Compared with women who were not current smokers, the relative risk of a diagnosed functional ovarian cyst among smokers was 2.0 (95% confidence interval 1.1-3.5). This finding, in an area of little previous research, provides a promising lead in the investigation of the etiology of functional ovarian cysts and the effects of smoking on ovarian function in general.

Adolescent↗
PubMed1994

Use of HPV 1 capsids produced by recombinant vaccinia viruses in an ELISA to detect serum antibodies in people with foot warts.

A sandwich ELISA was developed to detect HPV antibodies using HPV 1 capsids that were purified from recombinant vaccinia virus-infected cells and a monoclonal antibody to the HPV 1 L1 protein. Sera from 91 college-aged women who had been previously screened for HPV 1 antibodies by immune precipitation of capsid proteins were tested by ELISA. A cutoff point was established independently of other criteria based on the assumption that the ELISA values came from a mixture of two Normal distributions representing seropositive and seronegative individuals. It was found that the data fit this model best when the natural log of the ELISA (+0.5 to make all of the values positive) was used. Positive sera were shown to react with a conformational epitope(s) on the L1 protein. In the population reporting foot warts, 16 of 18 (89%) had ELISA values above the cutoff. This compared to 38 of 73 (53%) positives in the population reporting no history of foot warts. The odds ratio for the association of the ELISA reactivity with foot warts was 7.23 (95% CI 1.53, 69.4; P < 0.01). There was no significant association between the ELISA reactivity and wart infections reported at other sites. The average of the log ELISA values for individuals never reporting foot warts was -0.223 (SD 0.468), whereas the average value for individuals reporting foot warts within 10 years was 0.191 (SD 0.450) (P = 0.001). There was a negative correlation between the magnitude of ELISA reactivity and the time elapsed since the last appearance of foot warts. This apparent loss of seroreactivity over time may indicate that HPV 1 is usually eliminated from the host after infection or that inadequate levels of HPV 1 capsid antigen are produced during latent foot warts to maintain antibody levels.

Adolescent↗
PubMed1994

Aspartame ingestion and headaches: a randomized crossover trial.

To examine whether ingestion of aspartame is associated with headaches, we conducted a double-blind crossover study using volunteers with self-identified headaches after using aspartame. Of the 32 subjects randomized to receive aspartame (approximately 30 mg/kg/d) and placebo in a two-treatment, four-period crossover design, 18 completed the full protocol, seven completed part of the protocol before withdrawing due to adverse effects, three withdrew for other reasons, two were lost to follow-up, one was withdrawn due to noncompliance, and one withdrew and gave no reason. Each experimental period was 7 days long. Subjects reported headaches on 33% of the days during aspartame treatment, compared with 24% on placebo treatment (p = 0.04). Subjects who were "very sure" prior to the study that aspartame triggered some of their headaches reported larger treatment differences (aspartame = 0.37 headache-days, placebo = 0.18 headache-days; p < 0.001) than subjects who were "somewhat sure" (aspartame = 0.29 headache-days, placebo = 0.22 headache-days; p = 0.51) or "not sure" (aspartame = 0.33 headache-days, placebo = 0.39 headache-days; p = 0.51). There was no significant treatment difference in the length or intensity of headaches or in the occurrence of side effects associated with the headaches. This experiment provides evidence that, among individuals with self-reported headaches after ingestion of aspartame, a subset of this group report more headaches when tested under controlled conditions. It appears that some people are particularly susceptible to headaches caused by aspartame and may want to limit their consumption.

Adult↗
PubMed1994

Hormonal factors in vulvar cancer. A case-control study.

As part of a case-control study of vulvar cancer, we examined the role of reproductive history, menstrual history, exogenous estrogen use and body mass in the etiology of this disease. A total of 330 women with vulvar squamous cell cancer (259 in situ, 81 invasive), aged 18-79 years, who were diagnosed with this tumor during 1980-1990 were interviewed. Their responses were compared to those of 1,010 women who were selected from the general population by means of random digit dialing. Cases and controls did not differ regarding age at menopause, parity, number of prior pregnancies or number of prior births, history of miscarriage or use of noncontraceptive estrogens. Women diagnosed with vulvar cancer were slightly more likely to have experienced menarche at < 12 years (odds ratio [OR] = 1.8, 95% confidence interval [CI] = 1.2-2.7, in situ cancer; OR = 1.6, 95% CI = 0.8-3.1, invasive cancer), to have excess weight (invasive cancer only, OR = 2.9, 95% CI = 1.5-5.8 for highest tertile of Quetelet's index) and, among gravid women, to have had their first pregnancy after age 24 (in situ cancer only, OR = 1.5, 95% CI = 0.9-2.5). These data, together with similar results from previous studies and quantitative studies of hormone receptors in vulvar tissue, suggest that in situ and invasive vulvar cancer are not strongly hormone dependent tumors.

Adolescent↗
PubMed1993

A conditional analysis for two-treatment multiple-period crossover designs with binomial or poisson outcomes and subjects who drop out.

We propose a conditional analysis for outcome data on numbers of recurrent symptoms arising in a two-treatment, multiple-period crossover trial. Conditioning on subject-specific totals removes any dependence on mean subject-specific symptom rates and permits the use of standard software to perform regression analysis to examine treatment, period, carryover and interaction effects. The addition of offsets to the regression equations allows the incorporation of data from subjects who do not complete all periods in the trial. We apply the proposed method to data from a crossover trial and discuss its advantages and disadvantages.

Adult↗
PubMed1992

Descriptive epidemiology and survival analysis of nasopharyngeal carcinoma in the United States.

Population-based incidence data on nasopharyngeal carcinomas (NPC) from the Surveillance, Epidemiology and End Results program in the United States were examined for the years 1973-1986. The 1,645 cases showed incidence rates varying according to ethnic origin, with chinese having the highest, followed by Filipinos, Blacks and Whites. In females the incidence was about half of that seen in males, in each of these groups. There was no evidence of changes in incidence rates during the study period. An analysis of survival with NPC was undertaken using hazard function regression models to allow for control of multiple variables. Survival was found to be independently influenced by age and stage at diagnosis, histologic type, grade and sex. Significant ethnic differences in survival remained after adjustment for these factors, with Chinese surviving longest followed by Filipinos, Whites and Blacks. These difference in survival remained after control for the variation in population-wide mortality rates associated with age, ethnicity, sex and calendar year. We present evidence that survival has improved for this disease over time.

Adolescent↗
PubMed1992

Human papillomaviruses, herpes simplex viruses, and the risk of oral cancer in men.

A population-based case-control study was conducted in western Washington state to examine the relations between infection with human papilloma viruses (HPV), herpes simplex viruses (HSV), and risk of oral squamous cell cancer in men. Interviews were completed on 131 oral cancer cases diagnosed between January 1985 and December 1989 and 136 controls frequency matched to cases on age and date of diagnosis who were obtained by random digit dialing. The risk for oral cancer among men with 30 or more sexual partners was 2.4 times that of men with four or fewer partners (95% confidence interval (CI) 1.0-5.9). Men who ever practiced oral sex had lower risk for oral cancer relative to men who never practiced oral sex (relative risk (RR) = 0.4, 95% CI 0.2-0.8). Analyses of exfoliated oral cavity cells for the presence of HPV-6 DNA with polymerase chain reaction revealed that men with an oral HPV-6 infection had 2.9 times the risk for oral cancer of noninfected men (95% CI 1.1-7.3), whereas men with an oral HPV-16 infection had 6.2 times the risk for oral cancer of noninfected men (crude RR = 6.2, 95% CI 0.7-52.2). Relative risks associated with serologically detected HSV-1 and HSV-2 infections were 0.8 (95% CI 0.3-1.7) and 1.8 (95% CI 0.7-4.6), respectively. The authors conclude that HPV-6 is associated with oral cancer. Although men infected with HPV-16 and HSV-2 were at elevated risk, these associations may have been due to chance. The role of specific sexual practices in the transmission of viruses to the oral cavity remains unclear.

Antibodies, Viral↗
PubMed1992

Approaches to the analysis of case-control studies of the efficacy of screening for cancer.

To an increasing extent, case-control studies are being undertaken to determine if use of early detection procedures is associated with reduced mortality from cancer. The authors recommend that in such studies the analysis focus on screening activity in cases that occurs during an interval prior to diagnosis in which the cancer is believed to be detectable and still curable and to a corresponding time period in controls. This approach places a heavy burden on the investigator to estimate accurately the period during which the tumor ought to be detectable using the test in question and to sort out reliably tests done in response to signs or symptoms of the cancer from screening tests per se. Nonetheless, the authors feel that it offers the greatest ability to discern a true benefit of screening, while minimizing the numerous potential biases that can be present in this type of study.

Case-Control Studies↗
PubMed1992

Functional ovarian cysts in relation to the use of monophasic and triphasic oral contraceptives.

This population-based case-control study assessed the effect of current use of monophasic or triphasic oral contraceptives (OCs) on the risk of functional ovarian cyst development. The cases were all 15-39-year-old enrollees in the Group Health Cooperative of Puget Sound who had either an inpatient primary diagnosis of functional ovarian cyst in 1988 or 1989 (N = 67) or an outpatient primary diagnosis of functional ovarian cyst from March 1988 through August 1989 at one of five Group Health Cooperative primary care clinics (N = 39). Controls were randomly selected enrollees matched to the cases for age, primary care clinic, and enrollment date (N = 255). Subjects with previous hysterectomy or oophorectomy were excluded from this analysis. Pharmacy and medical record review showed that 16% of cases and 19% of controls were currently using monophasic OCs, whereas 11% of cases and 9% of controls were using triphasic OCs. Compared with women not using hormonal contraception, the relative risks of a diagnosed functional ovarian cyst among women currently using OCs were 0.8 (95% confidence interval [CI] 0.4-1.8) for users of monophasic OCs and 1.3 (95% CI 0.5-3.3) for users of triphasic OCs. In contrast to previous studies of monophasic OCs containing higher steroid dosages, the results of this study suggest that current use of low-dose monophasic OCs does not substantially decrease a woman's risk of functional ovarian cyst formation. In addition, our results do not support recent speculation that current use of triphasic OCs appreciably increases the risk of functional ovarian cysts.

Adult↗
PubMed1991

Progestagen supplementation of exogenous oestrogens and risk of endometrial cancer.

The favourable effects of exogenous progestagen on the endometrium are well known, but have not been adequately quantified with respect to endometrial cancer. The benefits of progestagen need to be weighted against its possible untoward effects on the risk of breast cancer and cardiovascular disease. A population-based case-control study of endometrial cancer was undertaken to evaluate the benefits of progestagen use. 158 incident cases were identified between 1985 and 1987 among women aged 40-64 years who were residents of King County, Washington. Detailed interviews were conducted and the responses were compared with those of 182 controls selected by random telephone digit dialling. The risk of endometrial cancer among women who had used unopposed oestrogen for more than 3 years was over five times that of women who had used no hormones (relative risk [RR] 5.7, 95% confidence interval [Cl] 2.5-12.8), whereas those who had also used a progestagen for at least six months of that time had an RR of only 1.6 (95% Cl 0.6-3.9). The RR differed according to days per month that progestagen was used: 2.4 (0.6-9.3) for progestagen use of less than 10 days per month versus 1.1 (0.4-3.6) for use of 10 or more days per month. These results provide additional evidence that the use of progestagen for 10 or more days per cycle can reduce the excess risk of endometrial cancer associated with long-term postmenopausal oestrogen use.

Adult↗