Height is not associated with long-term survival after acute myocardial infarction.

BACKGROUND: Studies show an inverse association between height and risk of myocardial infarction. How height affects survival after acute myocardial infarction is uncertain. METHODS: In the Determinants of Myocardial Infarction Onset Study, trained interviewers performed chart reviews and face-to-face interviews with 1935 patients hospitalized with acute myocardial infarction in 45 US medical centers between 1989 and 1993. We excluded 15 patients with missing information on height. After a search of the National Death Index for patients who died before 1996, we analyzed the relationship of height and survival with Cox proportional hazards regression. RESULTS: Of the 1920 eligible patients, 317 (17%) died during a median follow-up of 3.8 years. Height was positively associated with younger age, greater educational attainment, and a lower likelihood of being sedentary among both men and women. Height was not associated with long-term survival among women in unadjusted or adjusted analyses. Among men, height was associated with survival only in unadjusted analyses; adjustment for age eliminated this association. We found no relationship between height and survival in any individual age group among men or women. CONCLUSIONS: Although stature may be associated with the risk of acute myocardial infarction, it is not associated with long-term survival after such an event.

Impact of diabetes on long-term survival after acute myocardial infarction: comparability of risk with prior myocardial infarction.

OBJECTIVE: To determine the effect of diabetes on long-term survival after acute myocardial infarction and to compare its effect with that of a previous myocardial infarction. RESEARCH DESIGN AND METHODS: In a prospective cohort study, we followed 1,935 patients hospitalized with a confirmed acute myocardial infarction at 45 U.S. medical centers between 1989 and 1993, as part of the Determinants of Myocardial Infarction Onset Study. Trained interviewers performed chart reviews and face-to-face interviews with all patients. We analyzed survival using Cox proportional hazards regression to control for potentially confounding factors. RESULTS: Of the 1,935 patients, 320 (17%) died during a mean follow-up of 3.7 years. A total of 399 patients (21%) had previously diagnosed diabetes. Diabetes was associated with markedly higher total mortality in unadjusted (hazard ratio [HR] 2.4; 95% CI 1.9-3.0) and adjusted (1.7; 1.3-2.1) analyses. The magnitude of the effect of diabetes was identical to that of a previous myocardial infarction. The effect of diabetes was not significantly modified by age, smoking, household income, use of thrombolytic therapy, type of hypoglycemic treatment, or duration of diabetes, but the risk associated with diabetes was higher among women than men (adjusted HRs 2.7 vs. 1.3, P = 0.01). CONCLUSIONS: Diabetes is associated with markedly increased mortality after acute myocardial infarction, particularly in women. The increase in risk is of the same magnitude as a previous myocardial infarction and provides further support for aggressive treatment of coronary risk factors among diabetic patients.

Triggering myocardial infarction by marijuana.

BACKGROUND: Marijuana use in the age group prone to coronary artery disease is higher than it was in the past. Smoking marijuana is known to have hemodynamic consequences, including a dose-dependent increase in heart rate, supine hypertension, and postural hypotension; however, whether it can trigger the onset of myocardial infarction is unknown. METHODS AND RESULTS: In the Determinants of Myocardial Infarction Onset Study, we interviewed 3882 patients (1258 women) with acute myocardial infarction an average of 4 days after infarction onset. We used the case-crossover study design to compare the reported use of marijuana in the hour preceding symptoms of myocardial infarction onset to its expected frequency using self-matched control data. Of the 3882 patients, 124 (3.2%) reported smoking marijuana in the prior year, 37 within 24 hours and 9 within 1 hour of myocardial infarction symptoms. Compared with nonusers, marijuana users were more likely to be men (94% versus 67%, P<0.001), current cigarette smokers (68% versus 32%, P<0.001), and obese (43% versus 32%, P=0.008). They were less likely to have a history of angina (12% versus 25%, P<0.001) or hypertension (30% versus 44%, P=0.002). The risk of myocardial infarction onset was elevated 4.8 times over baseline (95% confidence interval, 2.4 to 9.5) in the 60 minutes after marijuana use. The elevated risk rapidly decreased thereafter. CONCLUSIONS: Smoking marijuana is a rare trigger of acute myocardial infarction. Understanding the mechanism through which marijuana causes infarction may provide insight into the triggering of myocardial infarction by this and other, more common stressors.

Prior alcohol consumption and mortality following acute myocardial infarction.

CONTEXT: Studies have found that individuals who consume 1 alcoholic drink every 1 to 2 days have a lower risk of a first acute myocardial infarction (AMI) than abstainers or heavy drinkers, but the effect of prior drinking on mortality after AMI is uncertain. OBJECTIVE: To determine the effect of prior alcohol consumption on long-term mortality among early survivors of AMI. DESIGN AND SETTING: Prospective inception cohort study conducted at 45 US community and tertiary care hospitals between August 1989 and September 1994, with a median follow-up of 3.8 years. PATIENTS: A total of 1913 adults hospitalized with AMI between 1989 and 1994. MAIN OUTCOME MEASURE: All-cause mortality, compared by self-reported average weekly consumption of beer, wine, and liquor during the year prior to AMI. RESULTS: Of the 1913 patients, 896 (47%) abstained from alcohol, 696 (36%) consumed less than 7 alcoholic drinks/wk, and 321 (17%) consumed 7 or more alcoholic drinks/wk. Compared with abstainers, patients who consumed less than 7 drinks/wk had a lower all-cause mortality rate (3.4 vs 6.3 deaths per 100 person-years; hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.43-0.71) as did those who consumed 7 or more drinks/wk (2.4 vs 6.3 deaths per 100 person-years; HR, 0.38; 95% CI, 0.25-0.55; P<.001 for trend). After adjusting for propensity to drink and other potential confounders, increasing alcohol consumption remained predictive of lower mortality for less than 7 drinks/wk, with an adjusted HR of 0.79 (95% CI, 0.60-1.03), and for 7 or more drinks/wk, with an adjusted HR of 0.68 (95% CI, 0.45-1.05; P =.01 for trend). The association was similar for total and cardiovascular mortality, among both men and women, and among different types of alcoholic beverages. CONCLUSION: Self-reported moderate alcohol consumption in the year prior to AMI is associated with reduced mortality following infarction.

Chromosome 4 deletions are frequent in invasive cervical cancer and differ between histologic variants.

OBJECTIVE: Patterns of discontinuous deletion of chromosome 4 have been described in histologic variants of lung carcinomas and may represent different "hotspot" targets for gene-environment interactions. Since similar environmental risks exist for cervical cancer, we investigated patterns of discontinuous deletion in two major histologic variants. METHODS: Thirteen archival cases of squamous cell cancer (SCCA) and 11 cases of adenocarcinoma (AC) were precisely microdissected. Matched normal and tumor DNA were used for polymerase chain reaction (PCR) based loss of heterozygosity (LOH) analyses using 19 polymorphic markers spanning chromosome 4. Human papillomavirus (HPV) detection was determined by PCR using general and type-specific primers (HPV 16, 18). Differences in LOH between histologic tumor types and chromosomal regions were determined using Fisher's exact test. RESULTS: Loss at any chromosome 4 locus occurred in 92% of all tumors studied, with the majority of deletions occurring on the long arm of the chromosome. Four discrete minimal regions of discontinuous deletion (R) were identified. For these regions, LOH frequencies were 76% (R1, 4q34-q35), 48% (R2, 4q25-q26), 36% (R3, 4p15.1-p15.3), and 26% (R4, 4p16). Loss in SCCA predominated at 4q (4q34-q35; 83%) and in AC at 4p (4p15.3; 50%). Overall LOH on the p arm was significant in AC (82%) compared to SCCA (31%) (P = 0.02). HPV detection was similar in SCCA (85%) and AC (73%), and HPV 16/18 subtypes were similarly represented in both histologies. CONCLUSIONS: Chromosome 4 deletions are frequent in cervical carcinomas. Different patterns of deletion between SCCA and AC may represent gene regions targeted by different gene-environment interactions in these tumor subtypes.

Increased risk of congestive heart failure among infarctions with nighttime onset.

BACKGROUND: The onset of acute myocardial infarction varies by time of day, with a peak in the morning and a trough at night. Whether infarct-related complications differ by the timing of the infarction is unknown. METHODS AND RESULTS: In the Determinants of Myocardial Infarction Onset Study, we performed chart reviews and face-to-face interviews with 3625 patients with acute myocardial infarction. We assessed the time of onset of symptoms, the presence of ventricular tachycardia or congestive heart failure, and peak creatine kinase levels (in 1043 patients). We found significant circadian variation in the risk of congestive heart failure (P =.001). The risk dropped from 17% for infarctions that began between 6 PM and midnight to 10% for infarctions that began between 6 AM and noon. Adjustment for differences in the time from symptom onset to presentation for care and use of thrombolytic agents did not change the results. We found no circadian variation in the risk of ventricular tachycardia or in peak creatine kinase levels. CONCLUSIONS: The risk of congestive heart failure is highest among infarctions that begin at night. Further research may clarify whether this reflects differences in the pathophysiologic characteristics of infarction or the quality of medical care provided for daytime and nighttime infarctions.

Lack of effect of recent alcohol consumption on the course of acute myocardial infarction.

BACKGROUND AND OBJECTIVE: Alcohol has marked effects on hemodynamic and hemostatic variables that might alter the presentation of acute myocardial infarction that follows its use. We sought to determine whether recent alcohol consumption alters the course or complications of acute myocardial infarction. METHODS: In the Determinants of Myocardial Infarction Onset Study, we performed chart reviews and face-to-face interviews with 2161 patients who did not receive thrombolytic therapy. We assessed alcohol use before infarction, peak creatine kinase levels (1043 patients), electrocardiographic interpretations (1408 patients), and the presence of ventricular arrhythmias or congestive heart failure (all patients). RESULTS: Among the 2161 patients, 399 (18.5%) drank alcohol within 24 hours before myocardial infarction. We found no significant difference in mean peak creatine kinase level between those who had recently used alcohol and those who had not in an adjusted comparison (-6.1% difference; 95% confidence interval [CI] -20.3%-10.7%; P =.46). We also found no differences in adjusted risk for Q-wave infarction, congestive heart failure, or ventricular arrhythmias (odds ratios 1.03 [95% CI, 0.73-1.45; P =.88], 1.01 [95% CI, 0.67-1.54; P =.95], and 1.04 [95% CI, 0.66-1.65; P =.86]). Categorization of the duration since last alcohol use into 6-hour intervals revealed no trends between time since last use of alcohol and any of these outcomes. CONCLUSIONS: Recent alcohol use is not associated with changes in infarct size or risk for Q-wave infarction, congestive heart failure, or ventricular arrhythmia among this population.

Triggering of myocardial infarction by cocaine.

BACKGROUND: Cocaine has been implicated as a trigger of acute myocardial infarction in patients with and those without underlying coronary atherosclerosis. However, the magnitude of the increase in risk of acute myocardial infarction immediately after cocaine use remains unknown. METHODS AND RESULTS: In the Determinants of Myocardial Infarction Onset Study, we interviewed 3946 patients (1282 women) with acute myocardial infarction an average of 4 days after infarction onset. Data were collected on the use of cocaine and other potential triggers of myocardial infarction. We compared the reported use of cocaine in the hour preceding the onset of myocardial infarction symptoms with its expected frequency by using self-matched control data based on the case-crossover study design. Of the 3946 patients interviewed, 38 (1%) reported cocaine use in the prior year and 9 reported use within the 60 minutes preceding the onset of infarction symptoms. Compared with nonusers, cocaine users were more likely to be male (87% vs 67%, P=0.01), current cigarette smokers (84% vs 32%, P<0.001), younger (44+/-8 vs 61+/-13 years, P<0.001), and minority group members (63% vs 11%, P<0.001). The risk of myocardial infarction onset was elevated 23.7 times over baseline (95% CI 8.5 to 66.3) in the 60 minutes after cocaine use. The elevated risk rapidly decreased thereafter. CONCLUSIONS: Cocaine use is associated with a large abrupt and transient increase in the risk of acute myocardial infarction in patients who are otherwise at relatively low risk. This finding suggests that studying the pathophysiological changes produced by cocaine may provide insights into the mechanisms by which myocardial infarction is triggered by other stressors.

Recent aspirin use is associated with smaller myocardial infarct size and lower likelihood of Q-wave infarction.

BACKGROUND: Controversy exists about the effect of recent aspirin use on infarct size and the likelihood of Q-wave infarction in patients who sustain myocardial infarction. METHODS: We performed face-to-face interviews and chart reviews on 3665 patients with acute myocardial infarction for the Determinants of Myocardial Infarction Onset Study. For the 2206 patients who did not receive thrombolytic therapy, we assessed aspirin use, peak creatine kinase levels (in 1043 patients), and electrocardiographic interpretations (in 1447 patients). RESULTS: Of the initial 1043 patients, 317 (30. 3%) subjects reported aspirin use in the 4 days before their infarction. The mean +/- SD peak creatine kinase level for aspirin users was 701 +/- 570 IU/mL versus 851 +/- 727 IU/mL for nonusers, an 18% difference (95% confidence interval [CI], 8% to 26%; P <.001). After adjustment for confounding factors, the difference was 12% (95% CI, 2% to 21%; P =.03). Similarly, 38.9% of the aspirin users and 48.7% of the nonusers sustained a Q-wave infarction, an odds ratio of 0.67 (95% CI, 0.54 to 0.83, P <.001). The adjusted odds ratio was 0.77 (95% CI, 0.61 to 0.97, P =.03). CONCLUSIONS: Recent aspirin use was associated with smaller infarct size and fewer Q-wave infarctions among this population of early survivors of acute myocardial infarction who did not receive thrombolytic therapy.

Endometrial cancer in polyps associated with tamoxifen use.

We report 5 cases of carcinoma arising within tamoxifen-associated endometrial polyps. In 4 of 5 cases there were no other changes within the endometrium. Given these findings, the sonohysterographic differentiation between a polypoid structure and thickened endometrium does not eliminate the need for histologic sampling of the uterine cavity.

Squamous metaplasia of the endometrium associated with HPV 6 and 11.

Although uncommon in the endometrium, squamous metaplasia, dysplasia, and squamous carcinoma have been observed. Associated human papillomavirus (HPV) infection is also unusual, due at least in part to the fact that HPV requires specific characteristics of the target epithelium for infectivity. We report a case of extensive squamous metaplasia with focal low-grade squamous intraepithelial neoplasia of the endometrium coexistent with low-grade cervical intraepithelial neoplasia and an invasive squamous carcinoma of the vagina. In situ hybridization studies revealed HPV types 6 and 11 in both the cervical and endometrial lesions. This is the first report to date to demonstrate squamous epithelial metaplasia and dysplasia of the endometrium, associated with HPV DNA of viruses typically of low oncogenic potential.

Educational attainment, anger, and the risk of triggering myocardial infarction onset. The Determinants of Myocardial Infarction Onset Study Investigators.

BACKGROUND: While it has recently been shown that anger may trigger the onset of acute myocardial infarction, there has been no study of the role of socioeconomic factors in such triggering. Socioeconomic factors, such as educational attainment, may modulate the risk of triggering because of their influence on individual reactivity to external stressors and on the prevalence of traditional cardiac risk factors. OBJECTIVE: To evaluate the influence of educational attainment on the relative risk of myocardial infarction onset following episodes of anger. METHODS: We interviewed 1623 patients (501 women) an average of 4 days following a myocardial infarction. Data were collected on standard demographic variables as well as risk factors for coronary artery disease. Educational attainment was categorized into 3 levels: less than high school, completed high school, and at least some college. Anger was assessed by the Onset Anger Scale, a single-item, 7-level, self-report scale. Occurrence of anger in the 2 hours preceding the onset of myocardial infarction was compared with its expected frequency using self-matched control data based on the case-crossover study design. RESULTS: The risk of having a myocardial infarction triggered by isolated episodes of anger declined consistently and significantly with increasing levels of educational attainment (P = .03). The relative risk was twice as high among those with less than high school education (relative risk, 3.3; 95% confidence interval, 2.0-5.4) compared with patients with at least some college education (relative risk, 1.6; 95% confidence interval, 0.9-2.9). CONCLUSIONS: These findings indicate that socioeconomic factors are potent modulators of the risk of triggering acute cardiovascular disease onset. A better understanding of the physiological mechanisms underlying this association may lead to novel approaches to prevent acute cardiovascular events.

Triggering myocardial infarction by sexual activity. Low absolute risk and prevention by regular physical exertion. Determinants of Myocardial Infarction Onset Study Investigators.

OBJECTIVE: To determine the relative risks of nonfatal myocardial infarction (MI) triggered by sexual activity among the general population and in patients with prior coronary heart disease. DESIGN: Relative risks and effect modification were calculated by the case-crossover method, a new epidemiologic technique designed to quantify the transient change in risk following exposure to a potential disease trigger. SETTING/PARTICIPANTS: A total of 1774 patients with MI were interviewed in 45 hospitals throughout the United States. Data were gathered on potential triggers of MI occurring immediately prior to the event and during the previous year. Results are presented for the 858 patients who were sexually active in the year prior to the MI, with attention to the 273 patients who had coronary artery disease prior to their index MI, and the effect of regular exertion on risk. MAIN OUTCOME MEASURE: The relative risk of nonfatal MI following sexual activity. RESULTS: Of the 858 patients, 79(9%) reported sexual activity in the 24 hours preceding MI, and 27(3%) reported sexual activity in the 2 hours preceding onset of symptoms of MI. The relative risk of MI occurring in the 2 hours after sexual activity was 2.5(95% confidence interval [CI], 1.7-3.7). The relative risk of triggering onset of MI among patients with a history of prior angina (2.1 [95% CI, 0.8-5.8]) or prior MI (2.9 [95% CI, 1.3-6.5]) was not greater than that observed in those without prior cardiac disease. Sexual activity was a likely contributor to the onset of MI in only 0.9% of cases and regular exertion was associated with decreasing risk. CONCLUSIONS: Sexual activity can trigger the onset of MI. However, the relative risk is low, and since the absolute hourly risk of MI is extremely low, the absolute risk increase caused by sexual activity also is extremely low (1 chance in a million for a healthy individual). Moreover, the relative risk is not increased in patients with a prior history of cardiac disease and regular exercise appears to prevent triggering. These findings should be useful for counseling patients and decreasing the fear of sexual activity that often prevents complete rehabilitation from cardiovascular disease.

Triggering of acute myocardial infarction onset by episodes of anger. Determinants of Myocardial Infarction Onset Study Investigators.

BACKGROUND: Many anecdotes and several uncontrolled case series have suggested that emotionally stressful events, and more specifically, anger, immediately precede and appear to trigger the onset of acute myocardial infarction. However, controlled studies to determine the relative risk of myocardial infarction after episodes of anger have not been reported. METHODS AND RESULTS: We interviewed 1623 patients (501 women) an average of 4 days after myocardial infarction. The interview identified the time, place, and quality of myocardial infarction pain and other symptoms, the estimated usual frequency of anger during the previous year, and the intensity and timing of anger and other potentially triggering factors during the 26 hours before the onset of myocardial infarction. Anger was assessed by the onset anger scale, a single-item, seven-level, self-report scale, and the state anger subscale of the State-Trait Personality Inventory. Occurrence of anger in the 2 hours preceding the onset of myocardial infarction was compared with its expected frequency using two types of self-matched control data based on the case-crossover study design. The onset anger scale identified 39 patients with episodes of anger in the 2 hours before the onset of myocardial infarction. The relative risk of myocardial infarction in the 2 hours after an episode of anger was 2.3 (95% confidence interval, 1.7 to 3.2). The state anger subscale corroborated these findings with a relative risk of 1.9 (95% confidence interval, 1.3 to 2.7). Regular users of aspirin had a significantly lower relative risk (1.4; 95% confidence interval, 0.8 to 2.6) than nonusers (2.9; 95% confidence interval, 2.0 to 4.1) (P < .05). CONCLUSIONS: Episodes of anger are capable of triggering the onset of acute myocardial infarction, but aspirin may reduce this risk. A better understanding of the manner in which external events trigger the onset of acute cardiovascular events may lead to innovative preventive strategies aimed at severing the link between these external stressors and their pathological consequences.

Erythropoietin levels during theophylline treatment in premature infants.

Mean erythropoietin levels were somewhat higher in premature infants receiving theophylline than in untreated infants with a comparable degree of anemia. These results differ from those in adults and may reflect the oxygenation of the theophylline-treated patients or the developmental regulation of erythropoietin production in response to adenosine receptor antagonists.

Triggering of acute myocardial infarction by heavy physical exertion. Protection against triggering by regular exertion. Determinants of Myocardial Infarction Onset Study Investigators.

BACKGROUND: Despite anecdotal evidence suggesting that heavy physical exertion can trigger the onset of acute myocardial infarction, there have been no controlled studies of the risk of myocardial infarction during and after heavy exertion, the length of time between heavy exertion and the onset of symptoms (induction time), and whether the risk can be modified by regular physical exertion. To address these questions, we collected data from patients with confirmed myocardial infarction on their activities one hour before the onset of myocardial infarction and during control periods. METHODS: Interviews with 1228 patients conducted an average of four days after myocardial infarction provided data on their usual annual frequency of physical activity and the time, type, and intensity of physical exertion in the 26 hours before the onset of myocardial infarction. We compared the observed frequency of heavy exertion (6 or more metabolic equivalents) with the expected values using two types of self-matched analyses based on a new case-crossover study design. The low frequency of heavy exertion during the control periods was validated by data from a population-based control group of 218 subjects. RESULTS: Of the patients, 4.4 percent reported heavy exertion within one hour before the onset of myocardial infarction. The estimated relative risk of myocardial infarction in the hour after heavy physical exertion, as compared with less strenuous physical exertion or none, was 5.9 (95 percent confidence interval, 4.6 to 7.7), Among people who usually exercised less than one, one to two, three to four, or five or more times per week, the respective relative risks were 107 (95 percent confidence interval, 67 to 171), 19.4 (9.9 to 38.1), 8.6 (3.6 to 20.5), and 2.4 (1.5 to 3.7). Thus, increasing levels of habitual physical activity were associated with progressively lower relative risks. The induction time from heavy exertion to the onset of myocardial infarction was less than one hour, and symptoms usually began during the activity. CONCLUSIONS: Heavy physical exertion can trigger the onset of acute myocardial infarction, particularly in people who are habitually sedentary. Improved understanding of the mechanisms by which heavy physical exertion triggers the onset of myocardial infarction and the manner in which regular exertion protects against it would facilitate the design of new preventive approaches.

A human adult Wilms' tumor. Histologic, ultrastructural, and cytogenetic analysis.

The cytogenetic, histologic, and electron microscopic studies of an adult patient with Wilms' tumor are presented. Wilms' tumor (nephroblastoma) is a common renal tumor of childhood but is extremely rare in people over 15 years old. The histologic analysis of the patient's tumor, including both light and electron microscopic analysis, indicated that this tumor satisfies the histologic criteria for an adult Wilms' tumor, namely, blastemic cells that are immature renal parenchymal cells, embryonic tubular structures, and a scanty stromal component consisting of loosely arranged spindle cells. The tumor showed several ultrastructural features characteristic of adult Wilms' tumor, namely, markedly elongated mitochondria, autophagic vacuoles, and intracytoplasmic filaments. Karyotypic analysis was performed on the patient's peripheral leukocytes and tumor cells. The leukocytes showed no significant increase in gaps and breaks, and the patient appears to have a normal male karyotype. Some interesting chromosomal anomalies were observed in the cultured tumor cells: at least one chromosome 13, both chromosomes 22, and the X chromosome are missing, three markers are present, and there is a possible deletion of 12p.

Erythropoietin-induced polycythemia in athymic mice following transplantation of a human renal carcinoma cell line.

An established cloned human renal carcinoma line RC-1, which has been continuously maintained in culture for several years and which produces erythropoietin, was injected s.c. into BALB/c athymic mice and produced tumors. Tumorigenicity was directly correlated with the number of RC-1 cells inoculated. Tumor cell histology resembled the original patient-derived tumor. Tumor-bearing mice developed hepatosplenomegaly and significant reticulocytosis with elevated hemoglobin and hematocrit values that were proportional to tumor mass. In addition, red cell mass and blood volume of nude mice increased over 100% as compared to control mice or to animals bearing nonrelevant neoplasms. Large amounts of immunoreactive erythropoietin could be extracted from the nude mouse RC-1 tumors. These results indicate that the RC-1 cell line is tumorigenic and produces biologically active erythropoietin in vivo in athymic mouse hosts, thus providing a reproducible model to study ectopic erythropoietin production and its regulation in vivo.

The heterogeneity of circulating human serum erythropoietin.

The presence of more than one form of immunoreactive erythropoietin was suggested by discrepancies between the levels of immunologically detectable and biologically active erythropoietin in the sera of normal individuals and patients with end-stage renal disease. In both groups, the level of immunologically detectable hormone was significantly higher than that of bioactive hormone. Sera from end-stage renal disease patients and normal subjects were fractionated on a gel permeation column, and the immunoreactive erythropoietin in the fractions was measured by RIA. Three classes of immunoreactive erythropoietin were found in the sera: one eluting before the [125I]erythropoietin marker, one coinciding with the [125I]erythropoietin marker, and a third eluting after the labeled tracer in the region of the cytochrome c marker. The high and low mol wt components were more immunoreactive than the human urinary erythropoietin standard in the RIA. Biological activity, as determined in the in vitro rat bone marrow assay, was found only in the material eluting with the erythropoietin tracer. These studies show that immunoreactive erythropoietin in the serum consists of three components with different immunoreactivities: high and low mol wt components and a component with a mol wt similar to that of the native hormone.