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M R Karagas

Publications and source records attributed to M R Karagas.

At least 19 recordsLinked to original sources
PubMed1999

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.

Adult↗
PubMed1999

Fracture risk in the U.S. Medicare population.

Using data from the 5% U.S. Medicare sample, we estimated the actuarial (life table) risk that a person aged 65 will fracture the upper or lower limbs or the pelvis, by age 75, 80, 85, and 90, taking into account the chance of dying in the interval. The actuarial risk of a 65-year old white woman sustaining a fracture by age 90 is 16% for the hip, 9% for distal forearm, 5% for proximal humerus, and 4% for ankle. Black women and white men have substantially lower risks, and the risks for black men are very low. Although hip fractures pose the single greatest risk, the risk of all other fractures combined is greater. White women have particularly high risks for all fractures, because of their longevity as well as their high fracture rates. It is important to adjust for the probability of dying when estimating risks in an elderly population.

Actuarial Analysis↗
PubMed1998

Design of an epidemiologic study of drinking water arsenic exposure and skin and bladder cancer risk in a U.S. population.

Ingestion of arsenic-contaminated drinking water is associated with an increased risk of several cancers, including skin and bladder malignancies; but it is not yet clear whether such adverse effects are present at levels to which the U.S. population is exposed. In New Hampshire, detectable levels of arsenic have been reported in drinking water supplies throughout the state. Therefore, we have begun a population-based epidemiologic case-control study in which residents of New Hampshire diagnosed with primary squamous cell (n = 900) and basal cell (n = 1200) skin cancers are being selected from a special statewide skin cancer incidence survey; patients diagnosed with primary bladder cancers (n = 450) are being identified through the New Hampshire State Cancer Registry. Exposure histories of these patients will be compared to a control group of individuals randomly selected from population lists (n = 1200). Along with a detailed personal interview, arsenic and other trace elements are being measured in toenail clipping samples using instrumental neutron activation analysis. Household water samples are being tested on selected participants using a hydride generation technique with high-resolution inductively coupled plasma mass spectrometry. In the first 793 households tested arsenic concentrations ranged from undetectable (0.01 microgram/l) to 180 microgram/l. Over 10% of the private wells contained levels above 10 microgram/l and 2.5% were above 50 microgram/l. Based on our projected sample size, we expect at least 80% power to detect a 2-fold risk of basal cell or squamous cell skin cancer or bladder cancer among individuals with the highest 5% toenail concentrations of arsenic.

Adult↗
PubMed1998

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.

Aged↗
PubMed1998

Effects of milk and milk products on rectal mucosal cell proliferation in humans.

Intake of dairy products and major dairy constituents (e.g., calcium) has been proposed to reduce the risk of colorectal cancer, although epidemiological studies have yielded inconclusive results. We conducted a randomized cross-over trial to test the effects of high- and low-dairy consumption diets on rectal mucosal proliferation, a possible intermediary marker for large bowel cancer. From a gastroenterology clinic at an academic medical center, we recruited 40 patients, ages 25-79 years, who had either a history of a large bowel adenoma or a first-degree relative with large bowel cancer. Participants completed a baseline questionnaire covering demographic characteristics, health history, and habits and a food frequency questionnaire. They were randomized to a 12-week diet of either high dairy intake (six dairy servings/day) or low dairy intake (<0.5 serving of dairy products/day), with an intervening 12-week washout period in which they were asked to resume their usual diet before crossing over to the alternate study diet for the last 12-week period of the study. Adherence to the study diets was monitored by a daily dairy intake checklist and periodic, unscheduled 24-h dietary recalls. Biopsies of the rectal mucosa were obtained at the beginning and end of each intervention phase. Two assays of rectal mucosal cell proliferation were performed: immunohistochemical determination of proliferating cell nuclear antigen and whole crypt mitotic count. We found no statistically significant changes in either of these proliferation measures as a result of high or low dairy intake. There was no correlation between the labeling index for proliferating cell nuclear antigen and whole crypt mitotic count; however, measures of the location and intensity of cell proliferation within the rectal crypt were highly correlated between the two assays. Thus, our study indicates that greater consumption of dairy products over a 12-week period does not change rectal mucosal cell proliferation.

Adult↗
PubMed1997

Ascorbic acid deficiency in porphyria cutanea tarda.

Porphyria cutanea tarda (PCT), the most common form of porphyria, is manifested as skin photosensitivity caused by excess hepatic production of uroporphyrin and heptacarboxylporphyrin. In experimental animal models, ascorbic acid modulates chemically induced uroporphyrin accumulation. The purpose of this study was to determine whether ascorbic acid is decreased in the plasma of patients with PCT. Plasma was obtained after an overnight fast from 21 PCT patients, 16 of whom were infected with hepatitis C virus (HCV), and from a separate group of 9 patients with HCV infection but not PCT. Thirteen PCT patients were studied when they had active disease and 8 after treatment-induced remission. Plasma ascorbic acid was low (<23 micromol/L) in 11 (85%) of the 13 untreated PCT patients and deficient (<11 micromol/L) in 8 (62%). Two patients with normal ascorbic acid levels (45 and 62 micrommol/L) had consumed multivitamins. In 2 patients with deficient ascorbic acid, plasma levels returned to normal after phlebotomy treatment. Of the 8 patients studied during remission, 4 had normal ascorbic acid values and 4 were deficient (5 to 8 micromol/L). Plasma ascorbic acid values were normal for all patients who had HCV but no PCT. These data suggest that plasma ascorbic acid concentrations are commonly low in PCT, but this decrease is unrelated to HCV infection. Ascorbic acid deficiency may be one of the factors that contributes to the pathogenesis of PCT.

Adult↗
PubMed1997

Risk of squamous cell carcinoma of the skin in relation to plasma selenium, alpha-tocopherol, beta-carotene, and retinol: a nested case-control study.

We conducted a nested case-control study of squamous cell skin cancer (SCC) to determine whether risk was related to plasma concentrations of selenium, alpha-tocopherol, beta-carotene, and retinol. We derived the study sample from participants in our Skin Cancer Prevention Study, all of whom had at least one basal cell or squamous cell skin cancer before study entry. Those who developed a new squamous cell skin cancer during the 3-5-year follow-up period were selected as cases (n = 132). Controls (n = 264) were chosen at random, with matching by age, sex, and study center, from among those who did not develop SCC but were being followed actively at the time the SCC case was diagnosed. Prediagnostic plasma samples were analyzed for alpha-tocopherol, beta-carotene, and retinol using high-performance liquid chromatography. Selenium determinations were made using instrumental neutron activation analysis. Odds ratios were computed using conditional logistic regression for matched samples. We found no consistent pattern of SCC risk associated with any of the nutrients examined. The odds ratios (95% confidence intervals) for the highest versus the lowest quartiles of beta-carotene, retinol, alpha-tocopherol, and selenium were 0.73 (0.38-1.41), 1.43 (0.77-2.64), 0.89 (0.43-1.85), and 0.86 (0.47-1.58), respectively. Thus, our data add to the growing body of evidence that these nutrients, at the concentrations we evaluated, are not related strongly to SCC risk.

Adult↗
PubMed1996

Risk of basal cell and squamous cell skin cancers after ionizing radiation therapy. For The Skin Cancer Prevention Study Group.

BACKGROUND: Human evidence that ionizing radiation is carcinogenic first came from reports of nonmelanoma skin cancers (NMSCs) on the hands of workers using early radiation devices. An increased risk of NMSC has been observed among uranium miners, radiologists, and individuals treated with x rays in childhood for tinea capitis (ringworm of the scalp) or for thymic enlargement; NMSC is one of the cancers most strongly associated with the atomic bombing of Hiroshima and Nagasaki. Although exposure to ionizing radiation is a known cause of NMSC, it is not yet clear whether therapeutic radiation causes both major histologic types of NMSC, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Additionally, the potentially modifying effects, such as latency, age when treated, and type of treatment, are not well understood. PURPOSE: We investigated the relative risks of BCC and SCC associated with previous radiation therapy and evaluated these risks in relation to age and time since initial treatment and the medical condition for which radiation therapy was given. METHODS: The study group comprised individual diagnosed with at least one BCC or SCC from January 1980 through February 1986, who were recruited to participate in a skin cancer prevention trial designed to test whether oral beta-carotene supplementation would reduce the risk of new NMSCs. Patients were identified through the dermatology and pathology records of academic medical centers in Hanover, NH; Los Angeles, CA; San Francisco, CA; and Minneapolis, MN. Each participant completed a questionnaire detailing lifetime residence, pigmentary characteristics, occupational and recreational sun exposure, and history of radiation therapy. At enrollment, a study dermatologist assessed skin type (tendency to burn or tan) and extent of actinic skin damage. Participants were followed with an annual dermatologic examination for an average of 4 years. Of the 5232 potentially eligible individuals, 1805 were enrolled in the trial. We excluded 112 patients who reported previous radiation therapy for skin cancer only and three with missing information on whether they were ever treated with radiation therapy, leaving 1690 patients for the analysis. Approximately 4% of the patients died or discontinued participation for other reasons during each study year. We examined time to occurrence of first new histopathologically confirmed BCC and SCC during the follow-up period in relation to history of radiation therapy (for reasons other than NMSC) using a proportional hazards model. A multiple end points survival model was used to compare the rate ratios (RRs) for BCC and SCC. We also used a longitudinal method of analysis to compute the RR of total new BCC and SCC tumors per person per study year associated with radiation therapy. Using this method, we additionally assessed the potential modifying effects of age at treatment, latency, and type of therapy. All P values were derived from two-sided statistical tests of significance. RESULTS: Among the participants we studied, 597 developed a new BCC (n = 1553 tumors) and 118 developed a new SCC (n = 179 tumors). The time to first new BCC, but not SCC, was associated with prior radiation therapy (RR = 1.7; 95% confidence interval [CI] = 1.4-2.0 and RR = 1.0; 95% CI = 0.6-1.7, respectively; P = .03 for the difference between the RRs). The RR of total BCC tumors was slightly higher (RR = 2.3; 95% CI = 1.7-3.1), but it was still unity for SCC (RR = 1.0; 95% CI = 0.5-1.9). BCC risk appeared to increase with younger age at exposure and time since initially treated, although these effects were only marginally statistically significant (P for trend = .06 and .07, respectively). Also, risk of BCC was more strongly related to treatment for acne (RR = 3.3; 95% CI = 2.1-5.2) than other conditions. CONCLUSIONS AND IMPLICATIONS: Our data suggest that exposure to therapeutic radiation is associated with BCC but not with SCC.

Adult↗
PubMed1996

Heterogeneity of hip fracture: age, race, sex, and geographic patterns of femoral neck and trochanteric fractures among the US elderly.

To explore potential etiologic differences in the two major types of hip fracture, the authors computed the incidence rates of fractures of the femoral neck and trochanteric region of the proximal femur using a 5 percent sample of the US Medicare population aged 65-99 years. For the period they examined, July 1, 1986, through June 30, 1990, the rates of both hip fracture types increased with age in all race and sex categories. The proportion of hip fractures that occurred in the trochanteric region rose steeply with age among white women, but not among black women, white men, or black men. Within the United States, a north-to-south gradient in rates of both fracture types was observed among women, while no clear pattern was found for men. These findings raise the possibility of etiologic differences in the two fracture types, and the results provide further evidence of sex and racial differences in the risk of osteoporotic fractures.

Black or African American↗
PubMed1996

Mortality associated with low plasma concentration of beta carotene and the effect of oral supplementation.

OBJECTIVE: To examine the relationship between beta carotene plasma concentration and beta carotene supplementation and risk of death from major disease causes. DESIGN: Cohort study of plasma concentrations; randomized, controlled clinical trial of supplementation. SETTING: Medical school-affiliated dermatology practices. PATIENTS: A total of 1188 men and 532 women with mean age of 63.2 years, who had enrolled in a randomized clinical trial of beta carotene supplementation to prevent nonmelanoma skin cancer. INTERVENTION: Oral beta carotene, 50 mg per day for a median of 4.3 years. MAIN OUTCOME MEASURES: All-cause mortality and mortality from cardiovascular disease and cancer. RESULTS: During a median follow-up period of 8.2 years, there were 285 deaths. Persons whose initial plasma beta carotene concentrations were in the highest quartile (>0.52 micromol/L [27.7 microg/dL]) had a lower risk of death from all causes (adjusted relative rate [RR], 0.52; 95% confidence interval [CI] 0.44 to 0.87) and from cardiovascular diseases (adjusted RR, 0.57; 95% CI, 0.34 to 0.95) compared with persons with initial concentrations in the lowest quartile (<0.21 micromol/L [11.2 microg/dL]). Patients randomly assigned to beta carotene supplementation showed no reduction in relative mortality rates from all causes (adjusted RR, 1.03; 95% CI, 0.82 to 1.30) or from cardiovascular disease (adjusted RR, 1.16; 95% CI, 0.82 to 1.64). There was no evidence of lower mortality following supplementation among patients with initial beta carotene concentrations below the median for the study group. CONCLUSIONS: These analyses provide no support for a strong effect of supplemental beta carotene in reducing mortality from cardiovascular disease or other causes. Although the possibility exists that beta carotene supplementation produces benefits that are too small or too delayed to have been detected in this study, noncausal explanations should be sought for the association between plasma concentrations of beta carotene and diminished risk of death.

Administration, Oral↗
PubMed1996

Patterns of fracture among the United States elderly: geographic and fluoride effects.

The purpose of this study was to examine whether geographic area or water fluoride were related to the occurrence of fractures among the elderly in the United States. We used a 5% sample of the white U.S. Medicare population, aged 65 to 89 years during the period 1986-1990, to identify fractures of the hip, proximal humerus, distal forearm, and ankle. The association of geographic region and fluoridation status with fracture rates was assessed using Poisson regression. We found that rates of hip fracture were generally lower in the northern regions of the United States and higher in the southern regions. For fractures of the distal forearm and proximal humerus, lower rates were found in the Western states, and higher rates in the East. No discernible geographic pattern was found for ankle fractures. Adjustment for water fluoridation did not influence these results. Independent of geographic effects, men in fluoridated areas had modestly higher rates of fractures of the distal forearm and proximal humerus than did men in nonfluoridated areas; no such differences were observed among women, nor for fractures of the hip or ankle among either men or women. In conclusion, our data suggest that fractures of the distal forearm and proximal humerus have etiologic determinants distinct from those of fractures of the hip or ankle.

Aged↗
PubMed1996

The epidemiology of peripheral fractures.

Although much is known about hip fracture epidemiology, there are relatively little data regarding fractures at other peripheral sites. Epidemiological differences between fractures are important, since they imply that an understanding of the consequences and clinical expression of osteoporosis requires the study of many different fracture types. Recent data regarding the basic epidemiology of limb fractures among the elderly in industrialized countries have made some patterns clear. Fractures outside the hip are relatively common events, and before age 70 to 75, ankle and distal forearm fractures occur more commonly than fractures of the hip. Among the elderly, fractures at the most proximal and most distal ends of the limbs have the highest incidence. Thus, in the upper extremity, fractures of the proximal humerus and distal forearm are the most common, while in the lower extremity, those at the hip and ankle predominate. Outside the axial skeleton, females have higher rates for most fracture types, and at most fracture sites whites have higher rates than blacks. In each limb, the most proximal fractures tend to have the most pronounced age-related increases in risk.

Aged↗
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↗
PubMed1996

Toenail samples as an indicator of drinking water arsenic exposure.

We conducted a pilot study to assess the utility of toenail arsenic concentrations as an indicator of ingestion of arsenic-containing water. We enrolled 21 individuals whose household drinking water supply was provided by a private well, including 10 individuals who lived in areas of New Hampshire where elevated water levels of arsenic had been reported previously. Participants were interviewed regarding use of their private (unregulated) wells for drinking and cooking, and each provided a sample of water and toenail clippings. All specimens were analyzed using instrumental neutron activation analysis with a sensitivity of approximately 0.001 parts per million (ppm). Trace concentrations of arsenic were detected in 15 of the 21 well water samples and in all toenail clipping samples. Among the 10 individuals who lived in areas with reportedly high arsenic levels in the water supply, the geometric mean toenail concentration was 0.39 ppm (SE, 0.12 ppm); among the other 11 persons, the geometric mean was 0.14 ppm (SE, 0.02 ppm; P = 0.005 for the difference between the two means). The overall Spearman correlation between toenail and well water arsenic was 0.67 (P = 0.009), and among those with detectable well water levels of arsenic, the Spearman correlation was 0.83 (P = 0.0001). Based on the regression analysis of those who had detectable water levels of arsenic, a 10-fold increase in well water concentrations of arsenic was reflected by about a 2-fold increase in toenail concentrations. These results indicate that concentrations of arsenic in toenails reflect use of arsenic-containing drinking water.

Adult↗
PubMed1994

Occurrence of cutaneous basal cell and squamous cell malignancies among those with a prior history of skin cancer. The Skin Cancer Prevention Study Group.

Non-melanoma skin cancer patients are believed to be at high risk of developing new skin malignancies; however, relatively few studies have actually examined this. Non-melanoma skin cancers, although generally not fatal, are responsible for significant morbidity and, if left untreated, can cause serious disfigurement and, in rare instances, death. Part of the difficulty in studying these tumors is that they are not routinely followed as rigorously as other cancers, and are excluded from most cancer registries. Prior studies have often included patients from a single dermatology practice of those treated with one type of therapy (e.g., Moh's surgery). Some studies did not entail active follow-up of patients but relied on reports to a registry or subsequent visits initiated by the patient or their physician. Other studies have been based solely on patients with complete follow-up information, excluding those who died or were lost to follow-up. Nearly all studies collected only a limited amount of information on each patient. In an attempt to overcome these limitations, we examined subsequent skin cancer occurrence among a group of patients followed as part of the Skin Cancer Prevention Study. In the following, we highlight some of the methodologic issues concerning the study of subsequent basal cell and squamous cell skin cancer risk, and the contribution of our work, along with that of others, in exploring clinical and etiologic questions pertaining to the occurrence of these malignancies.

Basal Cell Carcinoma↗
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↗
PubMed1993

Induction of labor and risk of sudden infant death syndrome.

OBJECTIVE: To investigate whether induction of labor is related to the occurrence of sudden infant death syndrome (SIDS) using a population-based, case-control study. METHODS: Cases comprised infants born between 1984-1988 in Washington state who died of SIDS according to their death certificate (ICD-9-CM 798.0) (N = 728). For comparison, we randomly selected a group of infants born in these same years who did not die of SIDS (N = 3021). Information regarding the pregnancy, labor, delivery, and condition of the newborn was obtained from the infants' birth certificates. RESULTS: Among the indications for induction that were examined, we found a slightly elevated risk of SIDS associated with advanced gestational age (greater than 41 completed menstrual weeks) (odds ratio [OR] 1.3, 95% confidence interval [CI] 1.0-1.8). A similar proportion of cases and controls had induced labors (OR 1.2, 95% CI 0.7-2.1). Although there was little or no apparent risk associated with induction among infants who had term gestations (37-41 completed menstrual weeks; OR 1.2, 95% CI 0.6-2.2), an increased risk was found among infants who had gestations of 42 weeks or greater (OR 3.0, 95% CI 0.7-12.5). We did not observe this trend with augmentation of labor. CONCLUSION: Our findings do not support an overall association between the methods used for induction of labor in the United States and the occurrence of SIDS. The elevated risk of SIDS observed in relation to induction of labor among infants who had post-term gestations raises the possibility that infants who do not spontaneously initiate labor may suffer some neuroregulatory or other abnormality involved in the pathogenesis of SIDS.

Adult↗