Histamine receptor antagonists and incident colorectal adenomas.

BACKGROUND: Prior studies suggest that histamines may modulate the development of colorectal neoplasia. AIM: To assess whether histamine receptor antagonist use was associated with adenoma formation. METHODS: Patients (n = 2366) were drawn from three adenoma chemoprevention trials. All underwent baseline colonoscopy with removal of adenoma(s) and were deemed free of remaining lesions; they were followed with surveillance colonoscopy. Medication use was assessed by questionnaire. Adjusted risk ratios for adenoma formation related to histamine receptor antagonist use (histamine H1 and H2 receptor, H1RA and H2RA) were determined using log linear models. RESULTS: In pooled analyses, H1RA exposure was not associated with subsequent adenoma risk (RR = 1.10; 95% CI 0.97-1.25) or multiple adenoma formation (RR = 0.85; 95% CI 0.67-1.07). H2RA use also was not associated with adenoma (RR = 0.90; 95% CI 0.77-1.06), or multiple adenoma (RR = 0.77; 95% CI 0.57-1.04) in the pooled analyses, but H2RA users in the first trial had a decreased risk of adenoma (RR = 0.70; 95% CI 0.48-1.03) and multiple adenoma (RR = 0.31; 95% CI 0.12-0.79). CONCLUSION: H2RA use was associated with reduced risk for adenoma in one trial, but not in the pooled analyses. Further study would be warranted before undertaking randomized trials of H2RAs for adenoma chemoprevention.

Effect of seeing tobacco use in films on trying smoking among adolescents: cross sectional study.

OBJECTIVE: To test the hypothesis that greater exposure to smoking in films is associated with trying smoking among adolescents. DESIGN: Cross sectional survey of 4919 schoolchildren aged 9-15 years, and assessment of occurrence of smoking in 601 films. SETTING: Randomly selected middle schools in Vermont and New Hampshire, USA. MAIN OUTCOME MEASURE: Number of schoolchildren who had ever tried smoking a cigarette. RESULTS: The films contained a median of 5 (interquartile range 1-12) occurrences of smoking. The typical adolescent had seen 17 of 50 films listed. Exposure to smoking in films varied widely: median 91 (49-152) occurrences. The prevalence of ever trying smoking increased with higher categories of exposure: 4.9% among students who saw 0-50 occurrences of smoking, 13.7% for 51-100 occurrences, 22.1% for 101-150, and 31.3% for >150. The association remained significant after adjustment for age; sex; school performance; school; parents' education; smoking by friend, sibling, or parent; and receptivity to tobacco promotions. The adjusted odds ratios of ever trying smoking for students in the higher categories of exposure, compared with students exposed to 0-50 occurrences of smoking in films, were 1.7 (95% confidence interval 1.2 to 2.4), 2.4 (1.7 to 3.4), and 2.7 (2.0 to 3.8). These odds ratios were not substantially affected by adjustment for parenting style or for personality traits of the adolescent. CONCLUSION: In this sample of adolescents there was a strong, direct, and independent association between seeing tobacco use in films and trying cigarettes, a finding that supports the hypothesis that smoking in films has a role in the initiation of smoking in adolescents.

A comparison of ink-directed and traditional whole-cavity re-excision for breast lumpectomy specimens with positive margins.

BACKGROUND: Excising a breast tumor with negative margins minimizes local recurrence. With a positive margin, the standard re-excision consists of excising the whole cavity and all surrounding breast tissue. By marking the sides of the lumpectomy specimen with six different colored inks, the surgeon can limit the re-excision to the involved margin. We compared the local recurrence rate after these two re-excision methods. METHODS: Records were reviewed of 527 women (546 breasts) treated with lumpectomy at two institutions. The log-rank test was used to compare the local recurrence-free survival. RESULTS: Of 546 tumors, 245 (45%) had negative margins on the initial lumpectomy and were not re-excised. Fifty-five percent had a positive or close margin; 181 underwent whole-cavity re-excision, and 120 had ink-directed re-excision. The mean follow-up time was 3.4 years. There was no significant difference in local recurrence for the patients whose initial margin was negative (3.7%) compared with the 243 patients with initially positive margins who underwent a re-excision (3.3%). Eleven of 181 (6%) patients undergoing a whole-cavity re-excision developed a local recurrence, compared with none of 120 (0%) patients with an ink-directed re-excision (P = not significant). Tissue mass excised was significantly smaller in the ink-directed group (23 vs. 83 g, P < .05). CONCLUSIONS: Ink-directed re-excision of lumpectomy specimens with positive margins minimizes the amount of breast tissue removed without increasing the incidence of local recurrence and is therefore preferable to the standard whole-cavity method.

Non-melanoma skin cancers and glucocorticoid therapy.

Non-melanoma skin cancer (NMSC) is an important cause of morbidity and long-term mortality in organ transplant recipients receiving immunosuppressive drugs such as azathioprine and cyclosporin, often combined with adrenocortical steroids (glucocorticoids). At lower doses, glucocorticoids alone are prescribed for other conditions including musculoskeletal, connective tissue and respiratory disorders. Presently, it is unknown whether patients taking glucocorticoids are at an increased risk of skin malignancies. In a population-based case-control study in New Hampshire, USA, we compared use of glucocorticoids in 592 basal cell carcinoma (BCC) and 281 squamous cell carcinoma (SCC) cases and in 532 age and gender matched controls; neither cases nor controls had a history of organ transplantation. Participants underwent a structured personal interview regarding history of medication use and skin cancer risk factors. We used unconditional logistic regression analysis to compute odds ratios associated with glucocorticoid use for 1 month or longer while controlling for potential confounding factors. Risk of SCC was increased among users of oral glucocorticoids (adjusted odds ratio = 2.31; 95% CI = 1.27, 4.18), and risk of BCC was elevated modestly (adjusted odds ratio = 1.49; 95% CI = 0.90, 2.47). In contrast, risk of both SCC and BCC were unrelated to use of inhaled steroids. Our data suggest that use of oral glucocorticoids may increase risk of NMSC, and SCC in particular, among patients other than organ transplant recipients. We hypothesize that immunosuppression induced by oral glucocorticoids may allow these cancers to emerge from immunosurveillance.

Children and guns in a well child cohort.

BACKGROUND: The purpose of this study was to estimate the extent of and to identify predictors of preadolescent gun use in a well child cohort with matched parent and child data. METHODS: We analyzed self-report questionnaires from children and their parents using conditional logistic regression models. Questionnaires were given to 3,145 ten- to twelve-year-old children and 3,145 parents enrolled by their pediatricians in a prevention cohort study. RESULTS: Thirty-two percent of the children lived in households with guns. Children and parents generally agreed about the presence of guns in their homes; 17% had access to unlocked guns in their homes; 22% had fired guns. In this preadolescent cohort, firing guns was associated with being male, having guns in the home, having friends who use guns, and initiation of alcohol use. CONCLUSIONS: In this well child cohort, significant numbers of preadolescent, healthy boys in white, middle-class U.S. homes have access to guns, are using guns, and have friends who use guns. These children are also early alcohol adopters. Safety interventions with parents of preadolescents about the risks for accidental injury, death, and suicide due to child gun use may prove beneficial.

Racial differences in pancreatic cancer: comparison of survival and histologic types of pancreatic carcinoma in Asians, blacks, and whites in the United States.

SEER data for histologically confirmed carcinomas of the pancreas for 1973-1995 from Hawaii, San Francisco, and Seattle (n = 10,621) were analyzed to compare the survival and types of carcinomas in various racial groups. These geographic sites were selected because each included a sizable number of Asian patients. The median survival after diagnosis in unadjusted data was longer in Asian patients than in whites. After adjustment for age at diagnosis and year of diagnosis, only the survival advantage of Asian women over whites and blacks persisted as a statistically significant difference. Racial differences were no longer statistically significant when further adjustments were made for stage, grade, and morphology. The proportion of papillary carcinomas or mucinous cystadenocarcinomas was higher in Asians than in whites and blacks (p = 0.02), and patients with these neoplasms had a longer median survival than did patients with ductal adenocarcinoma (12 vs. 3.3 months). The fraction of Asian patients with lower stages and grades of carcinomas also was higher than among white and black patients. Longer survival of Asian compared with white and black patients with pancreatic carcinoma is at least partly explained by their higher proportion of less aggressive carcinomas at the time of diagnosis.

Therapeutic ionizing radiation and the incidence of basal cell carcinoma and squamous cell carcinoma. The New Hampshire Skin Cancer Study Group.

OBJECTIVE: To estimate the relative risk of developing basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) after receiving therapeutic ionizing radiation. DESIGN: Population-based case-control study. SETTING: New Hampshire. PATIENTS: A total of 592 cases of BCC and 289 cases of SCC identified through a statewide surveillance system and 536 age- and sex-matched controls selected from population lists. MAIN OUTCOME MEASURES: Histologically confirmed BCC and invasive SCC diagnosed between July 1, 1993, through June 30, 1995, among New Hampshire residents. RESULTS: Information regarding radiotherapy and other factors was obtained through personal interviews. An attempt was made to review the radiation treatment records of subjects who reported a history of radiotherapy. Overall, an increased risk of both BCC and SCC was found in relation to therapeutic ionizing radiation. Elevated risks were confined to the site of radiation exposure (BCC odds ratio, 3. 30; 95% confidence interval, 1.60-6.81; SCC odds ratio, 2.94; 95% confidence interval, 1.30-6.67) and were most pronounced for those irradiated for acne exposure. For SCC, an association with radiotherapy was observed only among those whose skin was likely to sunburn with sun exposure. CONCLUSIONS: These results largely agree with those of previous studies on the risk of BCC in relation to ionizing radiation exposure. In addition, they suggest that the risk of SCC may be increased by radiotherapy, especially in individuals prone to sunburn with sun exposure. Arch Dermatol. 2000;136:1007-1011

Colorectal hyperplastic polyps and risk of recurrence of adenomas and hyperplastic polyps. Polyps Prevention Study.

We examined data from two large colorectal chemoprevention trials for possible associations of hyperplastic polyps and adenomas with subsequent development of these lesions. Hyperplastic polyps do not predict metachronous adenomas.

Increase in incidence rates of basal cell and squamous cell skin cancer in New Hampshire, USA. New Hampshire Skin Cancer Study Group.

We conducted a study to estimate the current incidence rates of basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC) of the skin in the population of New Hampshire (NH), USA, and to quantify recent changes in the incidence rates of these malignancies. BCCs and SCCs diagnosed among NH residents were identified through physician practices and central pathology laboratories in NH and bordering regions from June 1979 through May 1980 and from July 1993 through June 1994. For each diagnosis period, we estimated the age-adjusted incidence rates for both BCC and SCC among both men and women and for separate anatomic sites. Between 1979-1980 and 1993-1994, incidence rates of SCC increased by 235% in men and by 350% in women. Incidence rates of BCC increased by more than 80% in both men and women. While the absolute increase was greatest for tumors of the head and neck, the relative change was most pronounced for tumors on the trunk in men and on the lower limb in women. Thus, there has been a marked rise in the incidence rates of BCC and SCC skin cancers in NH in recent years. The anatomic pattern of increase in BCC and SCC incidence is consistent with an effect of greater sunlight exposure. Studies of BCC and SCC occurrence are needed to identify possible behavioral and environmental factors and to assess possible changes in diagnostic practices that might account for the rise in incidence of these common malignancies.

The colonoscopic miss rate and true one-year recurrence of colorectal neoplastic polyps. Polyp Prevention Study Group.

OBJECTIVE: Studies of tandem colonoscopies have reported that 15-25% of neoplastic polyps <1 cm in size and 0-6% of larger polyps are overlooked at the time of colonoscopy. We determined the miss rate and "true" 1-yr recurrence of neoplastic polyps in a population of patients reflecting a broad spectrum of different gastroenterology practice settings. METHODS: Patient data from several sources were examined for repeat colonoscopies performed on the same patient within 120 days of each other. Examination pairs were included for analysis if both colonoscopies had good preps and reached the cecum. The miss rate was calculated by two methods: 1) a pooled rate, the total number of polyps on all second examinations divided by the total number on both examinations, and 2) a within-person rate, the average of the individual miss-rates. We estimated a "true" 1-yr recurrence rate by subtracting the proportion of patients with a missed neoplastic polyp from the proportion of patients with a neoplastic polyp found at 1 yr. RESULTS: A total of 76 colonoscopy pairs a mean 47 days apart (range, 1-119 days) were identified from a total of approximately 15,000 examinations and used to calculate the overall miss rates. For the category "all polyps" (neoplastic and nonneoplastic polyps), 17% by the pooled method and 11% by the within-person method were missed. The corresponding rates for neoplastic polyps were 12% by the pooled method and 8% by the within-person method. A total of 17% of patients had one or more neoplastic polyps missed on the initial examination. The observed 1-yr recurrence rate was determined from 1,314 colonoscopy pairs performed a mean of 379 days apart and found to be 28% for neoplastic polyps. By comparing this to the proportion of patients with one or more missed neoplastic polyps, we found the true 1-yr recurrence of neoplastic polyps to be 11%. CONCLUSION: There is a significant colonoscopic miss rate for neoplastic polyps and "all polyps" in clinical practice that is comparable to that previously stated in special research settings. The within-person rate more accurately reflects the true colorectal polyp miss rate for any given colonoscopic exam than does the pooled rate. The difference between the observed 1-yr recurrence rate and the proportion of patients with a missed polyp represents the true 1-yr recurrence of neoplastic polyps.

Prevalence of mood disorders and utility of the PRIME-MD in patients undergoing radiation therapy.

PURPOSE: To validate a short, structured interview procedure that allows practicing oncologists to quickly and reliably identify mood disorders in their patients, and to estimate the prevalence and types of mood disorders in a radiation therapy patient setting, noting relationships between mood disorders and patient characteristics. METHODS: Consecutive, eligible adult patients from the practices of two radiation oncologists were administered the Primary Care Evaluation of Mental Disorders (PRIME-MD) by the treating physician. A subset of these patients was also evaluated with the SCID, administered by trained mental health care personnel. Agreement between the two instruments was examined using the kappa statistic. Prevalence of mood disorders was determined from the PRIME-MD. The significance of relationships between patient characteristics and mood disorders was examined by chi-square and ANOVA analysis, and subsequently by multivariate logistic regression analysis. RESULTS: One hundred twenty-two patients were studied. Fifty-three of these were administered the SCID. Agreement between the two instruments was very good (kappa = 0.70). A diagnosis of a depressive or anxiety disorder by the PRIME-MD was made in 59 of the 122 patients (48%, 95% confidence interval = 39%, 58%). Multivariate analysis showed that a diagnosis of a depressive mood disorder was significantly related to pain intensity and prior history of depression. CONCLUSION: We have demonstrated the validity and feasibility of the PRIME-MD administered by oncologists in making diagnoses of mood disorders. The prevalence of mood disorders in our set of patients undergoing a course of RT was nearly 50%. Future studies should describe the natural history of these disorders, and determine optimal intervention strategies.

Dietary and supplemental calcium and the recurrence of colorectal adenomas.

The association between calcium intake and the risk of colorectal neoplasia remains controversial. This analysis prospectively investigated the association between dietary and supplemental calcium intake and recurrent colorectal adenomas. Participants were part of a multicenter, randomized clinical trial of antioxidant vitamins. The study endpoints were adenomas detected between surveillance colonoscopies conducted at approximately 1 year and 4 years after study entry. Baseline intake of energy-adjusted calcium derived from a food frequency questionnaire was used as the main exposure of interest. Calcium supplement use was assessed by semiannual questionnaires. Logistic regression was used to compute odds ratios and 95% confidence limits, and Poisson regression was used to estimate rate ratios. Subjects in the fifth quintile of dietary calcium had an adjusted odds ratio of 0.72 (95% confidence interval, 0.43-1.22) compared to those in the lowest quintile. Investigation of the numbers of adenomas yielded stronger findings: the rate ratio for the fifth quintile versus the first was 0.63 (95% confidence interval, 0.39-1.02). Dietary calcium seemed to have a greater effect among individuals with a high-fat diet than among those with a low-fat diet; however, the interaction was not statistically significant. Use of calcium supplements was not related to adenoma recurrence. These results suggest that a high calcium intake may be associated with a reduction in risk of recurrent adenomas, especially among individuals on a high-fat diet.

Predictors of smoking cessation in adolescents.

OBJECTIVE: To examine factors associated with cessation of smoking in adolescents 12 to 18 years of age who smoke cigarettes. DESIGN AND SETTING: Prospective school-based cohort study of 1384 New Hampshire high school students surveyed at baseline and annually up to 3 subsequent years regarding their substance abuse behaviors, including adolescents who smoked 1 or more cigarettes within the past 30 days at baseline. OUTCOME MEASURES: Cessation behavior was defined by a subsequent response indicating nonsmoking status. We examined associations between smoking cessation and baseline measurements of the level of addiction (cigarette consumption pattern), experience with quitting, intent to quit now and in the future, opinion of adults smoking more than 1 pack of cigarettes per day, social influences to smoke, sex, and psychological attributes. RESULTS: Of 276 adolescents who qualified as cigarette smokers at baseline, 123 (44.6%) were occasional smokers, 65 (23.6%) were daily smokers of 1 to 9 cigarettes, and 88 (31.9%) were daily smokers of 10 or more cigarettes. While 39 (14.1%) had smoked for 1 year or less, 62 (22.5%) had smoked for 6 or more years. Seventy-five (27.2%) reported failed past attempts to quit smoking, 71 (25.7%) reported wanting to quit now, and 50 (18.1%) reported definitely intending to be a nonsmoker in the future. Seventy-nine smokers (28.6%) described themselves as nonsmokers in follow-up surveys. The smoking cessation rate was 46.3% among occasional smokers, 12.3% among daily smokers of 1 to 9 cigarettes, and 6.8% among daily smokers of 10 or more cigarettes. Smoking cessation was associated with occasional smoking status (adjusted odds ratio 6.67 compared with daily smokers of 10 or more cigarettes [95% confidence intervals, 2.26-19.69]), and definite intentions to quit in the future (2.67 [95% confidence intervals, 1.2-5.7]). Most of those with definite intentions to quit in the future were occasional smokers (92.0%). CONCLUSIONS: This study documents cessation of smoking in nearly one third of the adolescent smokers. The cessation rate among daily smokers of 10 or more cigarettes per day is comparable with adult cessation rates. Adolescents who are less addicted, measured by low frequency of cigarette use, are more likely than daily users to quit. In addition, definite intent to quit in the future predicts cessation, but only among occasional smokers. In contrast with adults, experience with quitting was not associated with a higher likelihood of cessation. Pediatricians should focus on keeping occasional smokers from moving into daily smoking status, where nicotine addiction begins to play a prominent role in maintaining the behavior. Further study is needed to guide enhancement of the recruitment of adolescents into cessation, assessment of nicotine dependence in daily adolescent smokers, and appropriate use of nicotine replacement therapy in this group.

Occurrence of other cancers among patients with prior basal cell and squamous cell skin cancer.

Epidemiological studies suggest that individuals with basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin are more likely to develop other malignancies; however, the factors responsible for this are unknown. To clarify the risk of other cancers following the occurrence of BCC and SCC, we followed participants in a multicenter skin cancer prevention trial for subsequent malignancies. The study group consisted of 1805 BCC and SCC patients who had enrolled in a trial testing the efficacy of oral beta-carotene. Medical confirmation was sought for all cancers (other than BCC or SCC), which were reported by participants or their next-of-kin over a follow-up period of 10 years. We computed the rate ratio (RR) and 95% confidence interval (CI) of time to first new, primary cancer in relation to history of BCC and SCC, using a proportional hazards model. A total of 235 participants had a new primary invasive cancer during 13,887 person-years of follow up. The risk of other cancers was modestly elevated in patients with one or more previous SCCs compared with those who only had a history of BCC (adjusted RR, 1.37; 95% CI, 0.91-2.07). Risk of other cancers also appeared to be increased among those who had multiple prior BCCs relative to those who had only one prior BCC (adjusted RR, 1.21; 95% CI, 0.91-1.61). Further adjustment for smoking history, Quetelet index, radiotherapy, extent of actinic skin damage, treatment assignment, or baseline beta-carotene concentrations did not appreciably alter the results. Cancer of the respiratory system was most strongly related to previous SCC or multiple BCC [RRs (95% CI), 2.20 (1.05-4.62) and 2.34 (1.14-4.83), respectively]. Our data suggest that unidentified exposures or inherited risk factors may play a common etiological role in the pathogenesis of nonmelanoma skin cancer and other cancers, especially respiratory cancers, although larger studies would be necessary to exclude the role of chance in these findings.

Folate intake, alcohol consumption, cigarette smoking, and risk of colorectal adenomas.

BACKGROUND: Recent evidence suggests that folic acid (and derivatives) could contribute to the protective effect of fruits and vegetables against the risk of large-bowel cancer. Other evidence indicates that alcohol drinking and cigarette smoking may impair the biologic actions of folate. We used data from an adenoma prevention trial to investigate the occurrence of colorectal adenomas (possible precursors of colorectal cancer) in association with folate intake, alcohol consumption, and cigarette smoking. METHODS: Patients with at least one recent large-bowel adenoma were followed with colonoscopy 1 year and 4 years after their qualifying colon examinations. Adenomas detected after the year 1 examination were used as end points. A food-frequency questionnaire was administered at study entry and at study completion; nutrient intake at study entry was used in this analysis. All statistical tests were two-sided. RESULTS: After adjustment for caloric intake, dietary folate had a significant protective association with the risk of recurrence of large-bowel adenoma (P for trend = .04). However, this inverse association was attenuated by further adjustment for intake of dietary fiber and fat. Use of folate supplements was not associated with a reduction in risk. Alcohol intake (seven or more drinks/week) was associated with increased risk (odds ratio = 2.04; 95% confidence interval = 1.28-3.26). Cigarette smoking, even smoking for long duration, was not related to adenoma recurrence. CONCLUSIONS: These data provide only modest support for previous findings suggesting beneficial effects of folate on colorectal adenoma risk. We find no evidence that cigarette smoking increases risk. These findings do suggest a substantial increase in risk with alcohol consumption.

Communication effectiveness training improves surgical resident teaching ability.

BACKGROUND: An important educational objective of academic surgical programs is to train surgical teachers. Whether formal instruction of surgery residents in general principles of teaching has a role in the achievement of this objective is unproven. STUDY DESIGN: We tested whether the teaching ability of surgery residents could be improved by two different interventions: (A) a lecture on communication effectiveness plus home study of their own videotaped lectures and (B) a critical review of their own videotaped lectures with a teaching consultant. Each resident taught four sessions. There was no intervention between sessions 1 and 2; intervention A occurred between sessions 2 and 3; and intervention B, between sessions 3 and 4. Each of the four videotaped sessions was graded for communication effectiveness using a standardized scoring form. RESULTS: There were no significant differences between scores from lectures 1 and 2 (no intervention) or lectures 2 and 3 (intervention A). Intervention B (individualized feedback) resulted in significant improvement in all scores from session 4 compared with sessions 1 and 2: content 3.40 versus 2.98 (p = 0.01), language 3.43 versus 3.22 (p = 0.03), delivery 3.25 versus 2.87 (p = 0.002), and overall 3.43 versus 2.88 (p = 0.002). CONCLUSIONS: Surgical resident teaching ability can be improved by communication effectiveness teaching. Individualized feedback is more effective than a lecture combined with self-study.

Effects of 4 y of oral supplementation with beta-carotene on serum concentrations of retinol, tocopherol, and five carotenoids.

beta-Carotene has been studied widely as a potential cancer-preventing agent. Recent studies found that subjects who took beta-carotene supplements orally had increases in their serum concentrations of alpha-carotene and lycopene that were large (> 150% increase) and significantly greater than such increases in subjects who received placebo and that similar supplementation was associated with a decrease of approximately 37% in plasma lutein concentrations. A biologic interaction between beta-carotene and other carotenoids was suggested. We measured concentrations of retinol, alpha-tocopherol, and five carotenoids in serum specimens from a random sample of subjects enrolled in a clinical trial of the use of antioxidant vitamins in preventing colonic adenomas. We used serum specimens obtained at enrollment and after the subjects took placebo (n = 54) or 25 mg beta-carotene/d (n = 54) orally for 4 y. In a multivariate analysis, baseline serum concentrations of the analytes, sex, body mass index, diet, smoking status, and age were associated with variable changes in some analytes over the 4-y period but supplementation with beta-carotene was related only to a mean increase in serum beta-carotene itself of 151%. We excluded with 95% confidence an increase in lycopene > 4.9%, an increase in alpha-carotene > 17.6%, and a decrease in lutein > 14.7% in subjects given beta-carotene. These results confirm previous findings that supplementation with beta-carotene given orally does not alter serum concentrations of retinol or alpha-tocopherol. The findings also indicate that beta-carotene supplementation, which results in a moderate increase in serum beta-carotene concentration, does not significantly change serum concentrations of other carotenoids.

Potential for an external vaginal antiitch cream containing benzocaine to cause methemoglobinemia in healthy women.

OBJECTIVES: Our purpose was to assess the potential for an external vaginal antiitch cream (20% benzocaine, 3% resorcinol) to significantly increase levels of methemoglobin above normal in healthy women. STUDY DESIGN: Fifty-five women reporting external vaginal itch were recruited for the study. Each patient was used as her own control with methemoglobin levels being measured before and after use of the cream. Women were instructed to apply a 1-inch strip of cream by fingertip to the external genital area three or four times a day for 7 consecutive days. RESULTS: There were no significant differences in methemoglobin levels before and after use or in levels from a subgroup of women aged > 50 years compared with levels in a younger population. CONCLUSIONS: This preparation appears to be safe when used as directed; however, the results cannot be extrapolated to the very young. Nevertheless, lavish or frequent application over wide areas of excoriation might lead to toxic concentrations and methemoglobinemia. Therefore patients with serious vaginal disease should be advised against self-treatment beyond the 7-day limit imposed by the Food and Drug Administration for over-the-counter external analgesic medications.

The significance of allelic deletions and aneuploidy in colorectal carcinoma. Results of a 5-year follow-up study.

BACKGROUND: A prospective study was initiated to analyze the prognostic value of both the deletion of candidate tumor suppressor genes and the DNA content in colorectal carcinoma specimens. METHODS: A prospective study was initiated in 1988, into which 104 patients from the Brooklyn VA Medical Center were accrued through March 1992. DNA restriction endonuclease digests, obtained by the Southern blot technique, were examined for allelic deletions by cDNA probes pnm23-H1 (17q21) YNZ 22.1 (17p13), and p15-65 (18q21). DNA content was measured by image analysis cytometry of Feulgen-stained tumor imprints. Median follow-up was 5.5 years (range, 4-8.5 years). RESULTS: Patients with nm23-H1 allelic deletions were 3 times as likely to develop distant metastases as patients without nm23-H1 deletions (relative risk [RR], 3.89; 95% confidence interval [CI], 1.39, 10.89). This connection was even stronger after adjustment for TNM stage and site of primary tumor (RR, 5.27; 95% CI, 1.67, 16.68). No significant association of 17p or 18q deletions or ploidy with either distant metastases or overall survival was noted. In multivariate analysis, clinicopathologic variables associated with decreased survival included intracellular mucin production, nuclear grade, TNM stage, and nerve invasion. CONCLUSIONS: A combination of clinicopathologic and molecular biologic variables may identify patients at high risk for death from disseminated colorectal carcinoma.