Temporal variations at the onset of spontaneous acute aortic dissection

There have only been a few studies of the chronobiological occurrence of acute aortic dissection (AAD), and most were international and multicentered. The aim of the present study, conducted at only one center, was to determine the most frequent daily, monthly, and seasonal occurrences of AAD. The study population included 204 patients (66.5% male) treated at our institute between January 1, 1998 and January 1, 2004. A significantly higher frequency of AAD occurred from 6:00 AM to 12:00 noon, compared with other time periods (P < 0.001). The results showed a significant circadian variation in AAD (P < 0.001) with a peak between 9:00 AM and 10:00 AM. No significant variation was found for the day of the week; however, AAD occurred most frequently on Wednesday and Monday. The frequency of AAD was found to be significantly higher during winter versus other seasons (P < 0.001). The analysis of monthly variations of the onset of AAD confirmed a peak in February (12.9%) and in January (12.3%). Similar to other cardiovascular diseases, AAD exhibits significant circadian and seasonal/monthly variations. Our findings indicate that the prevention of AAD, especially during the aforementioned vulnerable periods, is possible by adequate tailoring of the treatment of hypertension, which is the main AAD predisposing factor.     

Long-term follow-up of melatonin treatment in children with ADHD and chronic sleep onset insomnia

Abstract:  The thalamus has a strong nonphotic influence on sleep, circadian rhythmicity, pineal melatonin production, and secretion. The opening of the sleep gate for nonrapid eye movement sleep is a thalamic function but it is assisted by melatonin which acts by promoting spindle formation. Thus, melatonin has a modulatory influence on sleep onset and maintenance. A remarkable similarity exists between spindle behavior, circadian rhythmicity, and pineal melatonin production throughout life. Together, the thalamic and chronobiological control of sleep leads to a new and improved understanding of the pathophysiology of circadian rhythm sleep disorders and also of the principles of sleep hygiene interventions.     

Disrupted Circadian Rhythmicity of the Intestinal Glucose Transporter SGLT1 in Zucker Diabetic Fatty Rats

Background

Intestinal absorptive capacity shows a circadian rhythm synchronized with eating patterns. Disrupting these coordinated rhythms, e.g., with shift work, may contribute to metabolic disease. Circadian expression of nutrient transporters has not been studied in metabolic disease. We studied the circadian rhythm of intestinal transporter sodium glucose co-transporter type 1 (SGLT1) in an obese diabetic rat.

Methods

We compared obese Zucker diabetic fatty (ZDF) rats to lean ZDF littermates. Temporal feeding patterns were assessed, then rats were harvested at Zeitgeber (ZT, ZT0 = 7:00 a.m.) 3, 9, or 15 to measure insulin resistance, SGLT1 expression and intestinal glucose absorption capacity. Regulators of SGLT1 (sweet taste receptor T1R2/3; clock genes) were measured to elucidate underlying mechanisms.

Results

Both groups exhibited altered circadian food intake. Obese ZDF rats lost circadian rhythmicity of SGLT1 mRNA expression and functional activity. Lean ZDF rats maintained rhythmicity of SGLT1 mRNA expression but that of functional glucose absorption was blunted. Circadian rhythms of intestinal clock genes were maintained in both groups. Neither group had discernible rhythms of intestinal GLUT2 (glucose transporter) or T1R2 (sweet taste receptor component) mRNA expression. In summary, lean and obese ZDF rats exhibited similar disruptions in circadian feeding. Glucose intolerance was evident in lean rats, but only obese rats further developed diabetes and exhibited disrupted circadian rhythmicity of both SGLT1 mRNA expression and function.

Conclusions

Our findings suggest that disrupted circadian feeding rhythms contribute to glucose intolerance, but additional factors (genetics, changes in nutrient sensing/transport) are needed to lead to full diabetes.     

Tako-tsubo cardiomyopathy: is there a preferred time of onset?

The occurrence of major cardiovascular events is not randomly distributed over time, but exhibits chronobiological patterns, i.e., circadian, weekly, or seasonal. No systematic studies on the temporal preference of onset of Tako-tsubo cardiomyopathy (TTC) are known. We performed a computer-assisted search of the literature (from 2000 to January 2010), with the following search terms: transient left ventricular apical ballooning syndrome, takotsubo-like left ventricular dysfunction, ampulla cardiomyopathy, tako-tsubo or takotsubo cardiomyopathy, tako-tsubo, apical ballooning. Criteria for publication inclusion were (a) reporting of original data, (b) inclusion of at least 30 or more cases, (c) adherence to the requested diagnostic criteria for TTC. We focused on studies including in their purposes the “time of onset” of events. Out of the 19 studies found, 7 (4 from Europe, 1 each from Asia, Australia and USA) specifically addressed this aspect. A circadian (morning) and a seasonal (summer) higher frequency of events was found. TTC seems to exhibit a temporal variation of onset, with preferred peaks during morning and summer. Stress and catecholamines, also according to their temporal organization, might play a pivotal role. The demonstration of time frames characterized by highest frequency of occurrence might help to try to ensure maximal protection during particularly vulnerable periods.     

Gender Differences in the Circadian and Seasonal Variations in Patients with Takotsubo Syndrome: A Multicenter Registry at Eight University Hospitals in East Japan

Objective The aim of this study was to clarify the circadian and seasonal variations in addition to identify sex-based differences in Japanese patients with Takotsubo syndrome (TTS). Methods The authors conducted a retrospective observational study to analyse the differences between the groups based on sex. Patients The patients were registered out of each institute registry of the acute coronary syndrome (ACS) which contains a total of 10,622 cases in eight academic hospitals in east Japan. Results Data for 344 consecutive TTS (73 male and 271 female) were extracted from each hospital registry. In-hospital mortality was higher in the male group than in the female group (18% vs. 7%; p=0.005). With regard to the circadian variations in all study patients, TTS events occurred most often in the afternoon and least often during the night. Moreover, the patterns of circadian variations in the female and male groups were the same as that of all study patients. TTS events occurred most frequently in the autumn and least often in the spring in the whole study cohort. Moreover, the seasonal variation in the female group showed the same pattern as that of the whole cohort. However, there were no significant seasonal differences in the incidence of TTS in the male group. Conclusion In a multicenter study in Japan, seasonal variation was observed in the female group but not in the male group. Circadian variation was observed in both groups. These results suggested that the pathogenesis and clinical features of TTS might therefore differ according to sex.     

Circadian patterns in the onset of cardiogenic acute pulmonary edema

Background: Circadian patterns of onset favoring the morning hours have been demonstrated for many cardiovascular disorders. Although much is known about cardiogenic acute pulmonary edema (CAPE), the relationship between time of day and CAPE episode onset has not been previously studied. Methods: We examined 154 consecutive episodes of CAPE treated at an urban community hospital to determine whether circadian patterns existed in the time these episodes began. Results: For all episodes, a significant circadian pattern existed, with peak onset between 6:00 and 11:59 A.M. (p<0.01). When CAPE episodes were analyzed by the most probable precipitant of pulmonary edema, only the pattern for patients with progressive symptoms, showing a peak in the 6:00 and 11:59 A.M. interval, was statistically significant (p<0.01). Although a similar trend existed for CAPE occurring in association with acute myocardial infarction, the pattern fell short of statistical significance (p=0.09). Conclusions: These data suggest that circadian patterns favoring the morning hours exist for episodes of CAPE, and that patterns may vary depending on the precipitant of the episode.     

年龄与性别对大鼠收缩压和内皮源性血管活性物质昼夜节律的影响

背景已有研究发现年龄与性别可以对血压的昼夜节律产生一定影响,但这些因素对内皮素1与一氧化氮这两种重要的血管活性物质昼夜节律的影响尚缺乏充分研究。目的以不同年龄和性别的大鼠为实验对象,探讨收缩压、血液中内皮素1和一氧化氮的昼夜节律特征。方法选择SD大鼠128只,分为4大组,每组32只,分别为:①成年雄性鼠,即10周龄雄性大鼠。②成年雌性鼠,即10周龄雌性大鼠。③老年雄性鼠,即96周龄雄性大鼠。④老年雌性鼠,即96周龄雌性大鼠。适应性饲养8周后,采用鼠尾测压仪测定大鼠的收缩压后,并分别于不同时间点(2:00、8:00、14:00、20:00)处死大鼠,每个时间点处死每组中8只大鼠。并留取血,分别采用放免法和硝酸还原法检测血液中内皮素1、一氧化氮的含量。结果①与成年雄、雌性鼠相比,老年雄、雌性鼠各时间段收缩压均明显升高(P<0.01),其血液中内皮素1、一氧化氮均降低(P<0.05)。与成年雄性鼠相比,成年雌性鼠的收缩压及血浆内皮素1降低,血清一氧化氮增加(P<0.05);与老年雄性鼠相比,老年雌性鼠收缩压无明显变化(P>0.05),血液中内皮素1、一氧化氮均降低(P<0.05)。②4组大鼠收缩压、内皮素1及一氧化氮曲线的基本昼夜节律均存在。与成年鼠相比,老年鼠的收缩压峰值位相明显不同。成年雄性鼠与成年雌性鼠的收缩压峰值相位不同;而老年雄性鼠和老年雌性鼠收缩压峰值相位无明显变化。在4组大鼠血液中内皮素1和一氧化氮的峰值相位发生不同程度的移位,昼夜节律特征发生了明显变化。结论不同年龄和性别对于大鼠收缩压、血液中内皮素1和一氧化氮的时间生物学特征有影响。     

Cronobiología de la muerte en insuficiencia cardiaca

Introduction and objectives

In the general population, heart events occur more often during early morning, on Mondays, and during winter. However, the chronobiology of death in heart failure has not been analyzed. The aim of this study was to determine the circadian, day of the week, and seasonal variability of all-cause mortality in chronic heart failure.

Methods

This was an analysis of all consecutive heart failure patients followed in a heart failure unit from January 2003 to December 2008. The circadian moment of death was analyzed at 6-h intervals and was determined by reviewing medical records and by information provided by the relatives.

Results

Of 1196 patients (mean [standard deviation] age, 69 [13] years; 62% male), 418 (34.9%) died during a mean (standard deviation) follow-up of 29 (21) months. Survivors were younger, had higher body mass index, left ventricular ejection fraction, glomerular filtration rate, hemoglobin and sodium levels, and lower Framingham risk scores, amino-terminal pro-B type natriuretic peptide, troponin T, and urate values. They were more frequently treated with angiotensin receptor blockers, beta-blockers, mineralocorticoids receptor antagonists, digoxin, nitrates, hydralazine, statins, loop diuretics, and thiazides. The analysis of the circadian and weekly variability did not reveal significant differences between the four 6-h intervals or the days of the week. Mortality occurred more frequently during the winter (30.6%) compared with the other seasons (P = .024).

Conclusions

All cause mortality does not follow a circadian pattern, but a seasonal rhythm in patients with heart failure. This finding is in contrast to the circadian rhythmicity of cardiovascular events reported in the general population.Full English text available from:www.revespcardiol.org/en     

脂联素水平分泌的节律性及其与糖皮质激素、胰岛素、瘦素的关系

目的　观察库欣综合征患者、肥胖症者和正常人血清脂联素昼夜节律及糖皮质激素、胰岛素和瘦素对其影响。方法　 15例库欣综合征病人、10例单纯性肥胖症病人和 9例正常人 ,每 4h抽血 1次 ,测定 1d内的血清脂联素、皮质醇、胰岛素和瘦素的昼夜节律。同时观察地塞米松抑制试验对脂联素水平的影响。结果　库欣综合征病人、肥胖症者及正常人血清脂联素昼夜节律皆不明显 ,但肥胖症者 6个时间点脂联素水平显著低于正常人。脂联素曲线下面积与体重指数 (BMI)、腰围、腰臀围比和胰岛素曲线下面积呈显著负相关 (r值分别为 - 0 4 6、- 0 33、- 0 38、- 0 36 ,P值均 <0 0 5 ) ,而与瘦素的相关性尚未达到统计学差异 ,与皮质醇曲线下面积亦无相关性。 1、2、8mg地塞米松抑制试验对血清脂联素的影响皆不大 ,但库欣综合征病人术后第 1天脂联素水平明显低于术前。结论　血清脂联素水平与BMI、腰围呈负相关 ,既不受皮质醇昼高夜低的分泌节律影响 ,也不随餐后胰岛素释放的增加而变化 ,但术后的应激反应可能减少脂联素的分泌。     

Seasonal variations in variceal bleeding mortality and hospitalization in France

OBJECTIVES: The circadian variation in portal blood pressure and in the diurnal incidence of variceal bleeding is well known, but the seasonal variation in variceal bleeding is still controversial. This report analyzes the seasonal variations in mortality and hospitalizations due to variceal bleeding in the French population. METHODS: All the deaths due to variceal bleeding that occurred from 1987 to 1996 (N = 13,514) and all adults discharged from French public hospitals for variceal bleeding from 1995 to 1997 (N = 17,026) were examined retrospectively. Cumulated monthly averages were expressed as the percentage above or below the average monthly value during the entire study period. RESULTS: Deaths due to variceal bleeding in France occurred with a clear annual periodicity and peaked in winter (December/January), both in the overall population and in subgroups defined by age and sex, except for women. The distribution of cumulative monthly deaths differed by 24%, with a peak (14% above average) in December and a trough (10% below average) in July (Roger's test: p < 0.001). Hospitalizations for variceal bleeding in French public hospitals followed a similar seasonal pattern (p < 0.001) with a winter-spring predominance (4% to 7% from December through April), except in patients aged 15-49 yr. There was a short sharp peak of mortality in early winter in French public hospitals. The seasonality of hospitalization and death increased markedly with age. CONCLUSIONS: A better understanding of these age- and sex-specific seasonal patterns would allow to improve pharmacological protection measures, disease management, and educational strategies.     

THE CORRELATION BETWEEN SERUM AND SALIVARY MELATONIN CONCENTRATIONS AND URINARY 6-HYDROXYMELATONIN SULPHATE EXCRETION RATES: TWO NON-INVASIVE TECHNIQUES FOR MONITORING HUMAN CIRCADIAN RHYTHMICITY

Although there is a circadian rhythm in blood melatonin concentrations in humans, the problems associated with frequent blood collection limit the use of this rhythm in the investigation of the circadian system and in the diagnosis and treatment of chronobiological disorders. Therefore, to establish a convenient, non-invasive technique for monitoring melatonin circadian rhythmicity, we compared the melatonin concentrations in blood samples collected from five subjects every 2-4 h over a 26 h period, with the melatonin concentrations in saliva samples and with the total amount of 6-hydroxymelatonin sulphate excreted in the urine during 2-h periods. There was significant correlation between serum and salivary melatonin concentrations (r = 0.81, P less than 0.001), and between serum melatonin concentrations and 6-hydroxymelatonin sulphate excretion rates (r = 0.72, P less than 0.001). The results demonstrate that both salivary melatonin concentrations and urinary 6-hydroxymelatonin sulphate excretion rates are reliable indices of serum melatonin concentrations. These measurements, in combination with frequent sample collection, provide two convenient, non-invasive techniques for monitoring melatonin circadian rhythmicity.     

年龄对血清皮质醇和硫酸脱氢表雄酮水平及其昼夜变化的影响

目的　研究年龄对男性血清皮质醇和硫酸脱氢表雄酮 (DHEAS)水平及其昼夜节律的影响。方法　 2 6名男性健康志愿者按年龄 (每增龄 10岁 )分为四组 :3 0～ (8名 )、40～ (6名 )、5 0～ (5名 )和 60～(7名 )岁组。 8:0 0～ 2 2 :0 0每 2小时 ,2 2 :0 0～ 8:0 0每小时采血一次 ,ELISA检测血清皮质醇 ,化学发光免疫法检测血清DHEAS。结果　血清皮质醇和DHEAS水平均呈明显昼夜变化 ,余弦法证实有统计学意义。皮质醇峰值 4:0 0～ 6:0 0 ,谷值 18:0 0～ 2 4:0 0 ,较白种人的峰、谷时间提前约 2h ;DHEAS峰值在 16:0 0左右。年龄对血清皮质醇水平及其昼夜变化无明显影响 ,但影响血清DHEAS水平 ,60岁组的血清DHEAS水平较其它 3组明显降低 (P <0 .0 5或P <0 .0 1) ,皮质醇 /DHEAS比值也均显著增高 (均P <0 .0 1)。结论　年龄对血清皮质醇水平及其昼夜变化无明显作用 ,但明显影响血清DHEAS水平。     

Circadian and seasonal variations of ventricular tachyarrhythmias in patients with early repolarization syndrome and Brugada syndrome: analysis of patients with implantable cardioverter defibrillator

Circadian and Seasonal Variation in Early Repolarization Syndrome. Introduction: The circadian and seasonal patterns of ventricular tachyarrhythmia (VTA) in patients with early repolarization syndrome (ERS) have not been determined. We compared the timing of VTAs in patients with ERS and Brugada syndrome (BS). Methods and Results: We enrolled patients with ERS (n = 14) and BS (n = 53) who underwent implantable cardioverter defibrillator (ICD) implantation. The timing of VTAs, including cardiac arrest and appropriate shocks, was determined. During follow up of 6.4 ± 3.6 years in the ERS group and 5.0 ± 3.3 years in the BS group, 5 of 14 (36%) ERS and 10 of 53 (19%) BS patients experienced appropriate shocks (P = 0.37). Cardiac arrest showed a trend of nocturnal distribution peaking from midnight to early morning (P = 0.14 in ERS, P = 0.16 in BS). Circadian distribution of appropriate shocks showed a significant nocturnal peak in patients with ERS (P < 0.0001) but a trend toward a nocturnal peak in patients with BS (P = 0.08). There were no seasonal differences in cardiac arrest in patients with ERS and BS. However, patients with ERS showed a seasonal peak in appropriate shocks from spring to summer (P < 0.0001). There was no significant seasonal peak in patients with BS. The timing of VTAs (cardiac arrest plus appropriate shock) showed significant nocturnal distributions in patients with ERS and BS (P < 0.01, respectively). A significant clustering of VTAs was noted from spring to summer (P < 0.01) in patients with ERS, but not in patients with BS (P = 0.42). Conclusions: Incidence of VTAs showed marked circadian variations with night‐time peaks in patients with ERS and BS. (J Cardiovasc Electrophysiol, Vol. 23, pp. 757‐763, July 2012)     

Normative values for circadian and ultradian cardiovascular rhythms in childhood

To assess the prevalence and characteristics of physiological circadian (24-hour) and ultradian (12-, 8-, and 6-hour) rhythms of mean arterial blood pressure (BP) and heart rate (HR), we analyzed 24-hour ambulatory BP profiles from 938 healthy school children aged 5 to 18 years. Cosine harmonics were fitted by Fourier analysis, and an amplitude and acrophase (time of peak) were calculated for each rhythm. Ninety percent of children displayed circadian rhythmicity of BP, independent of age, whereas circadian HR rhythmicity decreased with puberty from 96% to 87% (P<0.0001). Puberty had marked effects on the prevalence of ultradian rhythmicity: 12- and 6-hour rhythms increased for BP (27% to 47%, P<0.0001; 18% to 25%, P=0.01) and HR (36% to 47%, 17% to 31%, both P=0.001), whereas 8-hour BP rhythms decreased (34% to 23%, P=0.002). Median amplitudes were 10.1, 5.9, 5.6, and 5.2 mm Hg for the 24-, 12-, 8-, and 6-hour BP rhythms, respectively, and 13.4, 7.7, 6.8, and 6.4 bpm for HR. The acrophase occurred at approximately 14:00 hours, 8:00 hours, 5:30 hours, and 2:00 hours (military time) for the four BP rhythms, and at 13:30 hours, 08:30 hours, 01:50 hours, and 02:00 hours for HR. For the combined curve, the peak-trough difference was 25.9 mm Hg and 35 bpm for BP and HR, respectively, with the peaks occurring at 13:50 hours and 13:10 hours. There was marked association between BP and HR rhythms, both for prevalence (P<0.0001 for coupling of BP and HR rhythms of the same period length) and timing, with a median time lag of BP after HR acrophase of only 21, 16, 13, and 5 minutes for the four rhythms, respectively.     

Dynamics of Centrocestus armatus Transmission in Endemic River in Hyogo Prefecture,Japan

Centrocestus armatus is an intestinal parasite belonging to the family Heterophyidae. We developed an apparatus for recovering cercariae and clarified the infection dynamics of this parasite. To clarify the circadian rhythm of cercarial shedding in the summer season, we filtrated 30 l of river water every 2 h for 24 h. Cercariae were first detected between 06:00 and 08:00 h, increased over time to reach peak at 16:00 h and decreased thereafter, thus showing a single-peak pattern. In a survey of seasonal change, approximately 200 cercariae were contained in 1 l of river water during the summer season, while none were found during the winter. This cercarial shedding pattern appeared to be related to sunrise/sunset and water/atmosphere temperature. Therefore, we examined whether cercarial shedding was affected by light or temperature changes under laboratory conditions, and confirmed that both light and temperature were important factors for cercarial shedding. Light was a stronger factor than water temperature. Cercarial shedding of C. armatus occurred in response to temperature and light. The change in the number of juvenile metacercariae detected in fish brain corresponded with monthly detection rates of cercariae; however, the incidence of new infections decreased in August. This suggests that Nipponocypris temminkii contains a defense mechanism against new infections that may have hindered the increase in parasite infectivity. These results clarified the smooth infection from the first to the second intermediate host of C. armatus in the endemic river. Throughout the study period, fecal samples were collected from 19 kites, 114 herons, and three unidentified species. However, our results using C. armatus showed a low value of 1% in herons and 5% in kites. The infection dynamics of final host to first intermediate host need to be further investigated.     

Persistence of circadian rhythmicity in a mammalian hypothalamic "island" containing the suprachiasmatic nucleus.

The experimental work described tested the prosposition that the suprachiasmatic nucleus of the hypothalamus is an autonomous circadian pacemaker. Simultaneous recording from two extracellular electrodes indicated neural (multiple unit) activity at two sites in the brain, one of which is in or near the suprachiasmatic nucleus and the other in one of many other brain locations. Both sites in intact rats displayed clear circadian rhythmicity of spontaneous neural activity. In experimental animals, a Halasz knife was used to create an island of hypothalamic tissue that contained the suprachiasmatic nuclei. In such animals that were also blinded by bilateral ocular enucleation, circadian rhythmicity was lost at all brain locations recorded outside the island, but it persisted within the island that contained the suprachiasmatic nuclei. The rhythmicity of the island is thus not dependent on afferent inputs from elsewhere in the brain.     

Seasonal changes in glycogen level and size of pinealocytes of the white-footed mouse, Peromyscus leucopus: a semiquantitative histochemical study

Glycogen level in and size of pinealocytes of the feral, white-footed mouse Peromyscus leucopus , were studied by a semiquantitative histochemical method to determine whether seasonal changes exist in them under natural conditions, what temporal pattern they exhibit, and whether 24-hour changes in these parameters exist in different seasons, as shown in the laboratory dd-mice. Marked seasonal changes were seen in both glycogen levels and nuclear densities (ANOVA P < 0.005). The size of pinealocytes at 09:00 to 10:00 showed one peak (and nadir) seasonal change, with the smallest size in winter (December and February) and a larger size in warmer seasons, with the maximum value in July. Glycogen level in pinealocytes at 09:00 to 10:00 showed bimodal seasonal changes, with lower levels in fall and spring and higher levels in winter and summer. In fall, a circadian trend in glycogen level in pinealocytes was seen, with a higher level at the end of the light period. In winter, the glycogen levels were very high at 09:00, 13:00, 17:00, and 21:00 examined and showed dampening of time-of-day differences. On the other hand, the size of pinealocytes followed a time-of-day change (P < 0.005), being largest at 13:00 and smallest at 21:00. Thus, marked changes in quantitative structure and chemical activities, suggesting changes in functional activity, in pinealocytes were noted especially in severe, cold winter.     

The seasonal risk of pediatric/juvenile acute lymphocytic leukemia in the United States

Acute lymphocytic leukemia (ALL) occurring in pediatric and juvenile patients of nine U.S.A. locations during 1973 through 1980 was investigated by epidemiologic methodology. Time series periodic regression analysis of the monthly cumulative risk for ages 0-19 years revealed evidence of trimodal periodicity at seven of the nine locations tested. Combined analyses revealed a significant effect of latitude in causing asynchrony of the trimodal patterns observed. The average risk maxima occurred in April, August, and December for U.S.A. locations with latitude above 40 degrees (Seattle, Nebraska, Iowa, Detroit, and Connecticut), and in February, July, and October for other locations (San Francisco, Utah, New Mexico, and Atlanta). Because periodic regression analysis is a complex method, independent validation tests were performed to supplement the original results. Here, the best symmetric trimodal sine curve model of each location was utilized to predict the average pattern among the remaining locations of similar latitude. These validation tests supported the existence of similar trimodal patterns for all of the southern locations, and all of the northern locations except Connecticut. The observed peaks in monthly ALL risk coincide with seasonal elevations in the rates of allergenic and infectious diseases, elements of which are capable of promoting lymphocytic proliferation and transformation. Annual disease rates were significantly lower in populations with a high proportion of Blacks or American Indians compared to predominantly Caucasian populations. The possibility that seasonal factors (environmental allergens and/or infectious agents) promote leukomogenesis via indirect mechanisms is briefly discussed.