Anti-Ia antibody in the sera of normal subjects after in vivo antigenic stimulation.

We showed that sera from normal subjects after antigenic challenge with intradermal PPD or Candida antigens or with subcutaneous tetanus vaccine contain a factor that blocks the binding of mouse monoclonal anti-Ia antibody to Ia-positive T cells or to B35 M cells, an Ia-positive human B cell line. The blocking activity appears 48 to 72 h after antigenic challenge and is gone by day 7. The appearance of the anti-Ia blocking activity coincided with a drop in the percentage of Ia-positive T cells and non-T cells in the peripheral blood of these subjects and also with a decrease in the density of surface Ia on the non-T cell population. The blocking was not genetically restricted; that is, serum from a given subject blocked anti-Ia binding to Ia-positive T cells of subjects with different DR haplotypes. The blocking activity was contained in the IgM fraction of the sera. The blocking activity of the sera was eliminated after absorption of the sera with Ia-positive but not with Ia-negative human cell lines. It would appear, therefore, that the blocking of monoclonal anti-Ia binding is caused by an IgM anti-Ia antibody that appears in normals after in vivo antigenic challenge.

Suppression of human T-cell mitogenesis by prostaglandin. Existence of a prostaglandin-producing suppressor cell.

Small amounts of PGE inhibit mitogen-induced [3H]thymidine incorporation in human peripheral lymphocytes. The 50% inhibitory concentration is approximately 10(-7) M, and this is reduced to approximately 10(-8) M when endogenous PGE production is blocked. PGE inhibits PHA- and Con A-stimulated cultures much better than PWM cultures, suggesting a differential effect of PGE on T-cell vs. B-cell function. In vitro blockade of PG synthesis results in approximately 50% increase in [3H]thymidine incorporation in PHA cultures. PGE is produced endogenously in PHA cultures by glass adherent suppressor cells.

Cyclic adenosine monophosphate response to prostaglandin E2 on subpopulations of human lymphocytes.

Receptors for prostaglandin E2 or histamine were measured on subpopulations of human lymphocytes, using the cyclic AMP increase after exposure to prostaglandin or histamine as an indicator for the presence of receptors. The cyclic AMP response to prostaglandin E2 was similar in unfractionated lymphocytes and the T-enriched and T-depleted fractions. Within the T-enriched population, T cells bearing a receptor for the Fc portion of IgG (T gamma-cells) had a 27.4-fold rise in cyclic AMP after exposure to prostaglandin E2, whereas the remaining T cells (non-T gamma cells) had a fourfold increase. It would appear that prostaglandin receptors are concentrated on a small subfraction of T gamma cells, comprising approximately 15% of the T-cell population. The cyclic AMP response to histamine was less than twofold in all lymphocyte fractions.

Sensitivity of lymphocytes to prostaglandin E2 increases in subjects over age 70.

We examined the sensitivity of lymphocytes from different age groups to inhibition by prostaglandin E2. Phytohemagglutinin-stimulated cultures of peripheral blood mononuclear cells from 12 healthy subjects over the age of 70 were much more sensitive to inhibition by exogenously added prostaglandin E2 than were cells from 17 young controls (ID50 congruent to 10 nM for the subjects over 70 vs. greater than 3 micronM for the young controls). The more senstivie lymphocytes from a subject over 70 were to prostaglandin E2, the lower was his or her response to phytohemagglutinin (r = 0.75, P less than 0.01). The mean responses to phytohemagglutinin of the peripheral blood mononuclear cells from the subjects over 70 were significantly depressed compared to the young controls. Addition of indomethacin, a prostaglandin synthetase inhibitor, to the cultures resulted in an increase in [3H]thymidine incorporation of 140 +/- 16% in the cells of the subjects over 70 vs. a 36 +/- 3% increase in the young controls (mean +/- SEM, P less than 0.001). The mean phytohemagglutinin response of the subjects over 70 was 40% of the control response without indomethacin. With addition of indomethacin the response of subjects over 70 rose to 72% of control. Thus, increased sinsitivity to prostaglandin E2 appears to be responsible in part for the depressed mitogen response of peripheral blood mononuclear cells from healthy subjects over 70.

Control of polyclonal immunoglobulin production from human lymphocytes by leukotrienes; leukotriene B4 induces an OKT8(+), radiosensitive suppressor cell from resting, human OKT8(-) T cells.

We report that leukotriene B4 (LTB4), a 5-lipoxygenase metabolite of arachidonic acid, is a potent suppressor of polyclonal Ig production in pokeweed mitogen (PWM)-stimulated cultures of human peripheral blood lymphocytes, while LTC4 and LTD4 have little activity in this system. Preincubation of T cells with LTB4 in nanomolar to picomolar concentrations rendered these cells suppressive of Ig production in subsequent PWM-stimulated cultures of fresh, autologous B + T cells. This LTB4-induced suppressor cell was radiosensitive, and its generation could be blocked by cyclohexamide but not by mitomycin C. The LTB4-induced suppressor cell was OKT8(+), while the precursor for the cell could be OKT8(-). The incubation of OKT8(-) T cells with LTB4 for 18 h resulted in the appearance of the OKT8(+) on 10-20% of the cells, and this could be blocked by cyclohexamide but not by mitomycin C. Thus, LTB4 in very low concentrations induces a radiosensitive OKT8(+) suppressor cell from OKT8(-) cells. In this regard, LTB4 is three to six orders of magnitude more potent than any endogenous hormonal inducer of suppressor cells previously described. Glucocorticosteroids, which block suppressor cell induction in many systems, may act by inhibiting endogenous production of LTB4.

Prostaglandin suppression of mitogen-stimulated lymphocytes in vitro. Changes with mitogen dose and preincubation.

In this study we further characterize the properties of the prostaglandin-producing suppressor cell. Overnight preincubation of peripheral blood mononuclear cells results in an increased response of the cells to phytohemagglutinin or Concanavalin A compared to the response of fresh cells. This increase in mitogen response with preincubation was similar in magnitude to the increase in mitogen response of fresh cells after the addition of indomethacin. The two manipulations were not additive; that is, after preincubation, indomethacin caused much less enhancement of mitogen stimulation of peripheral blood mononuclear cells (100 +/- 12% increase before preincubation vs. 12 +/- 6% after preincubation; mean+/-SEM, P < 0.001). Preincubated cells also lose sensitivity to inhibition by exogenous prostaglandin E(2). It requires the addition of 100- to > 1,000-fold more exogenous PGE(2) to produce comparable inhibition of phytohemagglutinin-stimulated preincubated cells than is required for inhibition of phytohemagglutinin-stimulated fresh cells. The enhancing effect of indomethacin increases with decreasing doses of phytohemagglutinin. Indomethacin causes a 1,059+/-134% increase in [(3)H]thymidine incorporation at the lowest dose of phytohemagglutinin (0.2 mug/ml), and a 4+/-3% increase at the highest dose (20 mug/ml). This increase in response to indomethacin with a lower dose of phytohemagglutinin is due to increased sensitivity to inhibition by PGE(2) at lower mitogen doses. The prostaglandin-producing suppressor cell assay and the short-lived suppressor cell assay measure over-lapping phenomena. The increased suppressive effect of the prostaglandin-producing suppressor at suboptimal mitogen dose must be taken into account in the interpretation of any study where the response to a range of mitogen doses is studied.

Mechanism of action of glucocorticosteroids. Inhibition of T cell proliferation and interleukin 2 production by hydrocortisone is reversed by leukotriene B4.

The mechanism whereby glucocorticosteroids are immunosuppressive is unknown. One potential mechanism of action of these compounds is inhibition of arachidonic acid metabolism. We found that the inhibition of lymphocyte proliferation by hydrocortisone or dexamethasone was mimicked by nonspecific lipoxygenase inhibitors and also by a specific 5-lipoxygenase inhibitor, but not by a specific cyclooxygenase inhibitor. Mitogen-stimulated cultures of T cells produce approximately 5 X 10(-9) M leukotriene B4 (LTB4) in 24 h. This production of LTB4 is completely inhibited by concentrations of hydrocortisone or lipoxygenase inhibitors that inhibit mitogen-induced [3H]thymidine incorporation. The inhibition of lymphocyte proliferation by either hydrocortisone or by the 5-lipoxygenase inhibitor was totally reversed by LTB4 but not by leukotriene C4 or leukotriene D4. LTB4 had no effect on the inhibition of lymphocyte proliferation by noncorticosteroids such as prostaglandin E2, histamine, or gamma-interferon. The inhibition of interleukin 2 (IL-2) production by hydrocortisone or dexamethasone was also completely reversed by exogenous LTB4. LTB4 alone did not cause IL-2 production or cell proliferation when added to resting lymphocytes. Thus, endogenous LTB4 production appears to be necessary but not sufficient for phytohemagglutinin-induced IL-2 production and lymphocyte proliferation. Glucocorticosteroids inhibit IL-2 production and lymphocyte proliferation by inhibiting endogenous LTB4 production.

Anti-Ia reactivity in sera from patients with systemic lupus erythematosus.

Antileukocyte antibodies in sera from patients with systemic lupus erythematosus (SLE) were characterized by determining cross-reacting specificies with the antigens defined by OKT3, OKT4, OKT8, OKM1 and anti-Ia hybridoma antibodies (Abs). T cells were prepared by sheep erythrocyte (E) rosetting after removal of adherent cells. T cells, or non-T cells, were preincubated with SLE sera at 4 degrees C and then with monoclonal Abs. Binding by specific monoclonal Abs was assessed by two methods: rosetting with ox erythrocytes conjugated with goat anti-mouse IgG and also in the fluorescence-activated cell sorter using fluorescein isothiocyanate-conjugated goat anti-mouse IgG. Using the rosetting method, we found that sera from SLE can block the binding of monoclonal mouse hybridoma anti-Ia Abs to T cells; the blocking of other monoclonal Abs was not consistent. Using fluorescence-activated cell sorter analysis, preincubation with SLE sera lowered the intensity of staining and total percentage of either T or non-T cells stained by monoclonal anti-Ia Abs. Blocking of anti-Ia Abs binding by SLE sera was not histocompatibility leukocyte antigen (HLA)-DR restricted and was not due to Fc receptor binding. These results indicated that antibodies in SLE sera react with structures contiguous to or identical with Ia determinants. Anti-Ia activities in SLE sera correlate with SLE disease activity. In addition, there was a significant negative correlation between anti-Ia blocking activity in the sera and the percentage of Ia-positive T cells in the blood of SLE patients. Antibodies in SLE sera with anti-Ia blocking activity may play an important role in immune dysregulation in SLE patients.

Determinants of survival in older cancer patients.

BACKGROUND: We and others have previously described a number of characteristics that are associated with delays in diagnosis and increased risk for inadequate treatment of older women and men with cancer. These characteristics include poor social support, limited access to transportation, and impaired cognition. However, there is little information on how these factors influence survival of older cancer patients. PURPOSE: The purpose of the study was to determine which patient characteristics predicted survival up to 10 years after the diagnosis of cancer. METHODS: In 1984, we initiated a population-based study of men and women who were 65 years of age or older, living in a six-county area of New Mexico, and newly diagnosed with cancer. For 646 individuals with cancer of the breast (n = 188), prostate (n = 247), or colon or rectum (n = 211), we assessed patient baseline characteristics, disease stage at diagnosis, and adequacy of treatment (definitive or nondefinitive) as determinants of survival for up to 10 years following diagnosis. Multivariate survival models were used to analyze the data; all P values were two-sided. RESULTS: In multivariate analyses, we first included all patient characteristics, except the stage at diagnosis and the adequacy of treatment. In this initial analysis, the following were among variables that were significantly associated with patient survival: age, education, cancer knowledge, ethnic group, and cognitive status. When stage at diagnosis and adequacy of treatment were added to the model, both advanced stage at diagnosis (hazard ratio = 1.7 [95% confidence interval ¿CI¿ = 1.3-2.1] for diagnosis at regional stage versus local stage; hazard ratio = 3.0 [95% CI = 2.0-4.7] for distant stage versus local stage) and inadequate treatment (hazard ratio = 1.6 [95% CI = 1.1-2.3]) were associated with poor survival. However, adding stage at diagnosis and adequacy of treatment to the analysis had little influence on the magnitude of the effect of patient characteristics on survival. In separate analyses of patient data by cancer site, receipt of nondefinitive therapy was associated with increased mortality among patients with colon/rectal cancer (hazard ratio = 7.8 [95% CI = 2.8-21.4]) and breast cancer (hazard ratio = 2.2 [95% CI = 1.1-4.3]) but not among patients with prostate cancer (hazard ratio = 1.0 [95% CI = 0.6-1.9]). CONCLUSIONS: Advanced stage at diagnosis and inadequate treatment of older cancer patients are associated with poor survival. Impaired cognition and inadequate education in elderly patients are also associated with poor survival. This decreased survival does not appear to be a consequence of known barriers to health care that are responsible for delays in diagnosis and for inadequate treatment. IMPLICATIONS: Efforts to facilitate early diagnosis and receipt of definitive treatment for cancer in older individuals may improve their survival.

Delay in seeking care for cancer symptoms: a population-based study of elderly New Mexicans.

To characterize the delay by the elderly in seeking care for cancer symptoms, we interviewed 800 New Mexicans, greater than or equal to 65 years of age, with newly diagnosed cancer. Overall, 29.4% of the subjects were asymptomatic when cancer was detected, and 48.0% presented within 2 months of symptom onset. However, 19.2% of the subjects delayed seeking care for at least 12 weeks and 7.4% delayed at least 1 year. Site of cancer was the strongest determinant of delay. Hispanics tended to report longer delay than non-Hispanics, and age was not associated with delay. Of the numerous other factors considered, only having a regular checkup was significantly associated with delay interval.

Survival of American Indian and Hispanic cancer patients in New Mexico and Arizona, 1969-82.

Survival was examined by ethnic group for 31,465 incident cancer cases diagnosed from 1969 through 1982 in Hispanic and non-Hispanic whites residing in New Mexico and in American Indians residing in New Mexico and Arizona. In comparison with the 1- and 5-year survival rates following the diagnosis of cancer for non-Hispanic whites, those for American Indians were generally poorer and, to a lesser extent, those for Hispanics were also poorer. The American Indian and Hispanic patients tended to have more advanced disease at the time of diagnosis, although this pattern was not consistent across all sites. For many primary cancer sites, American Indian patients were less likely to receive treatment for their cancer than were non-Hispanic whites. Hispanics were also less likely to be treated for cancers of some sites, although the differences were not as large as for American Indians. However, after adjustment for stage and treatment, American Indians demonstrated significantly poorer survival than non-Hispanic whites for cancers of many sites. After adjustment for stage and treatment, survival in Hispanics was generally comparable to that in non-Hispanic whites.

Breast cancer care in old age: what we know, don't know, and do.

In this review of current pertinent literature from the fields of cancer epidemiology, oncology, health services research, and geriatrics, we describe the epidemiology and unique features of breast cancer and its victims in old age. In addition, we review the current evidence regarding treatment efficacy (i.e., beneficial under ideal circumstances) and effectiveness (i.e., beneficial under usual circumstances) in relation to primary tumor management and the use of adjuvant therapy in early stage disease and outline the challenges associated with studying breast cancer care in older women (> or = 65 years of age). Comorbidity, impaired functional status, lack of social support, and differences in host physiology are among the many factors that influence treatment efficacy and effectiveness, making extrapolation of study findings from younger to older women questionable. Indeed, with the exception of studies of adjuvant tamoxifen therapy, none of the clinical trials supporting the 1990 National Institutes of Health Consensus Development Conference on Treatment of Early-Stage Breast Cancer guidelines have included women over the age of 70 years. Because (a) breast cancer is becoming increasingly common in old age and (b) health-related quality of life is frequently more important to older women than is risk of recurrence or death, all three aspects (surgical management of the primary tumor, postoperative irradiation, and axillary lymph node dissection) of recommended primary treatment deserve fresh scrutiny. The value of adjuvant chemotherapy has yet to be defined. Substantial variations in breast cancer diagnosis, treatment, and care exist, and these differences become greater with increasing age of the patient. However, evidence regarding the reasons for these variations and their relationships with subsequent outcomes is lacking. Challenges for investigators in studies of older women include recruitment into studies, collection of reliable data from interviews or surveys, measurement of disease severity and comorbidity, and selection of relevant outcomes. Given current uncertainty about optimal treatment, clinicians can best serve older patients with early stage breast cancer by involving them in decision-making, taking into account available efficacy data, and individualizing care on the basis of such factors as comorbidity, social support, functional status, and patient preferences for outcomes. Future studies of treatment efficacy in older women should examine the roles of radiation therapy and axillary lymph node dissection that follow breast-conserving therapy and should focus on quality of life in addition to recurrence and mortality. Less aggressive treatments, tamoxifen therapy, and adjuvant chemotherapy should also be evaluated.

Patterns of use of chemotherapy for breast cancer in older women: findings from Medicare claims data.

PURPOSE: There is little population-based information available on the use of chemotherapy in women with breast cancer. This study describes the use of chemotherapy through analysis of Medicare claims and determines the correlates of chemotherapy use. PATIENTS AND METHODS: We used the merged Surveillance, Epidemiology, and End Results-Medicare database and identified women > or = 65 years of age diagnosed with breast cancer in 1991 and 1992. Chemotherapy was ascertained from Medicare claims through procedure codes for chemotherapy made within 24 months of the diagnosis. RESULTS: In women with stages I, II, III, and IV breast cancer, the percentage receiving chemotherapy within 24 months of diagnosis was 5.1%, 19.5%, 33.9%, and 35.2%, respectively. Most women receiving chemotherapy had two to 12 claims; the median number was eight. Use of chemotherapy decreased significantly with age across all tumor stages; eg, in women with stage III cancer, the use of chemotherapy declined from 49% in those aged 65 to 69 years to 10% in those > or = 80 years old. In a multivariate analysis, there was little variation by ethnicity. Chemotherapy use was highest (70%) in women aged 65 to 69 years with node-positive and estrogen receptor-negative tumors and lowest (5%) in those with node-negative and estrogen receptor-positive tumors. Compared with those without comorbid diseases, patients with a comorbidity score of 2 had significantly lower use of chemotherapy. CONCLUSION: Medicare claims data seem to provide valuable information on the use of chemotherapy for breast cancer in older women. However, external validation of the accuracy and completeness of these data is required before any firm conclusion can be drawn.

A population-based study of functional status and social support networks of elderly patients newly diagnosed with cancer.

We assessed the functional status and social support networks of 799 men and women aged 65 years or older newly diagnosed with cancer and living in six New Mexico counties. Functional limitations included depending on others for transportation (33%) and mental incompetence or poor recent memory (42%). The percentage of patients with functional limitation increased sharply with increasing age. In a substantial number of patients there was also evidence for poor social support networks; 26.5% of subjects lived alone and 38.9% had no children living in the vicinity. In a multiple logistic regression analysis, the predictors of having a poor social support network included non-Hispanic white ethnicity, advanced age, low income, and being a recent migrant to the area. Subjects with functional limitations were more likely to have poor social support networks than subjects without such limitations. The deleterious combination of impaired functional status and a limited social support network may explain why elderly cancer patients are at increased risk for not receiving appropriate therapy. Given the potential complexities involving the evaluation and appropriate treatment of cancer, care must be taken to adequately assess functional status and support mechanisms of older patients, and to provide adequate support to ensure compliance with treatment.

Hearing and cognition in the elderly. New findings and a review of the literature.

The purpose of this study was to determine the relationship between hearing status and cognitive status initially and at 5-year follow-up in a cohort of healthy elderly men and women and to relate the results to published reports on this topic. Volunteers older than 60 years with no major illnesses and taking no long-term prescription medications were examined. Baseline testing of hearing and cognition was performed in 224 subjects; 112 subjects underwent cognitive testing at 5-year follow-up. Hearing was measured by the Speech Perception in Noise test; cognition was measured by two parts of the Wechsler Memory Scale and by the Jacobs Cognitive Screening Test, an oral screening instrument. At baseline there were small correlations between hearing acuity and memory scores, but these disappeared after adjustment for age and gender. Analysis of follow-up memory and cognitive screening test scores in relation to baseline hearing ability showed no correlation between hearing at entry and cognitive function at 5 years. In addition, baseline hearing level did not predict change in memory or cognitive screening test scores during the follow-up period. The power of the study was 90% to detect a correlation of .30 between measures of hearing and cognition. There was no evidence for a major effect of hearing acuity on cognitive function over time in this group of healthy elderly. Review of published studies suggests that hearing ability is related to cognitive status in demented subjects, but there is little to suggest that in the normal elderly, hearing impairment leads to cognitive decline.

Cancer treatment protocols. Who gets chosen?

We compared the age distribution of all adults in New Mexico with cancer incident from 1959 through 1982 with that of all adult New Mexican patients enrolled in cancer treatment protocols sponsored by the Southwest Oncology Group (New Mexico). For all cancer sites, elderly patients were substantially underrepresented in the Southwest Oncology Group protocols. While 31% of all adult patients with cancer were over age 70 years, only 7% of patients with cancer enrolled in Southwest Oncology Group protocols were in that age group. The underrepresentation of elderly individuals in cancer treatment protocols will make it difficult to determine optimal therapies for older patients with cancer.

Frequent hypoglycemic episodes in the treatment of patients with diabetic ketoacidosis.

BACKGROUND: Previous studies of the management of diabetic ketoacidosis have noted a wide range of incidence of hypoglycemia but have not studied the risk factors associated with it. METHODS: To describe the incidence of hypoglycemia in patients hospitalized with diabetic ketoacidosis, we retrospectively reviewed the charts of all adult patients with the diagnosis of diabetic ketoacidosis at three private, community hospitals in Milwaukee, Wis, between January 1, 1987, and May 31, 1990. Two hundred twenty admissions in 150 patients met our inclusion criteria. RESULTS: In 30% (66/220) of cases of diabetic ketoacidosis, a serum glucose level or Accu-Chek (Boehringer-Mannheim, Indianapolis, Ind) finding was 2.7 mmol/L or less during the first 14 days of hospitalization. No factors could be identified that were associated with a significantly increased risk of early hypoglycemia (within the first 48 hours of admission). The risk of a "late" occurrence of hypoglycemia (after 48 hours of hospitalization) was increased by fever (relative risk, 2.05; 95% confidence interval [CI], 1.16 to 3.63), "nothing orally" status (relative risk, 3.01; 95% CI, 1.88 to 4.83), hepatic disease (relative risk, 2.56; 95% CI, 1.39 to 4.70), and renal disease (relative risk, 2.07; 95% CI, 1.26 to 3.39). A logistic regression analysis showed "nothing orally" status to be associated with an increased risk of any hypoglycemia occurring during the hospitalization (relative risk, 2.39; 95% CI, 1.63 to 3.51). Physicians and nurses documented the first episode of hypoglycemia in their notes 45.5% and 80.3% of the time, respectively. CONCLUSION: Hypoglycemia is still a common complication of diabetic ketoacidosis, is associated with hepatic and renal disease as well as fever and "nothing orally" status, and is not documented well in physician notes.

Effect of social support on stress-related changes in cholesterol level, uric acid level, and immune function in an elderly sample.

Strong social support systems, which in epidemiologic studies are associated with decreased morbidity and mortality, have been hypothesized to mitigate the harmful effects of stressful stimuli on the individual. The authors found that, among 256 healthy elderly adults, individuals with good social support systems tended to have lower serum cholesterol and uric acid levels and higher indices of immune function; these correlations were independent of age, body mass, tobacco use, alcohol intake, and degree of perceived psychological distress. Thus, social support systems may intervene between the stressful stimulus and the physiologic response to that stimulus.

Social, psychological and physical factors affecting the nutritional status of elderly subjects: separating cause and effect.

The fact that most of the important changes in nutritional status with age are not secondary to aging per se in no way detracts from their importance. This paper reviews three factors that can affect nutritional status in elderly adults: ethanol intake, cognitive status, and institutionalization. The discussion focuses on the difficulties in obtaining reliable information on the interaction of nutritional status with these factors.

Nutritional status in a healthy elderly population: riboflavin.

Riboflavin status in 270 free-living and healthy elderly was determined from dietary intake (3-day food records) and erythrocyte glutathione reductase activity coefficients (EGR-AC). High EGR-ACs (greater than 1.35) indicate poor riboflavin nutriture. Mean dietary intakes of riboflavin were 1.86 +/- 0.64 (SD) for males and 1.58 +/- 0.69 mg/day for females. Approximately 45% of the population were taking some supplemental riboflavin and total riboflavin intakes ranged from 0.65 to 165 mg/day. The mean EGR-AC for those taking supplemental riboflavin was significantly lower than that of the nonsupplemented group (1.06 and 1.16, respectively). Only three subjects had EGR-ACs greater than 1.35. A significant correlation was found between total riboflavin intake and EGR-AC (r = 0.53). In a separate population of 667 volunteers between the ages of 20 and 87 yr, a significant decrease in mean EGR-AC with age was found. The mean EGR-AC for those over 60 yr and not taking a supplement was 1.16 +/ 0.10 compared to 1.23 +/- 0.11 for those from 20 to 29 yr old. Inadequate riboflavin nutriture appears to be more of a problem for younger than older adults.