Biphasic effects of postnatal exposure to diethylhexylphthalate on the timing of puberty in male rats

Phthalate esters such as di(2-ethylhexyl)phthalate (DEHP), which are commonly found in cosmetics and in flexible plastics distributed by the food, construction, and medical products industries, have been classified as anti-androgens. High-dose DEHP exposure in utero is associated with decreased androgen levels. However, when administered after birth, low doses of DEHP (eg, 10 mg/kg body weight) may stimulate androgen production. In the present study, the potential of phthalate exposure to advance or delay the timing of puberty was assessed. Male Long-Evans rat pups were chronically subjected to low or high doses of DEHP, with the androgen-driven process of preputial separation serving as an index of pubertal timing. Rats were treated with 0, 10, 500, or 750 mg/kg body weight DEHP for 28 days starting at day 21 postpartum. The average age at which the animals completed preputial separation was measured in each group. The age of preputial separation was 41.5 +/- 0.1 days postpartum in controls (vehicle). The 10 mg/kg DEHP dose advanced pubertal onset significantly to 39.7 +/- 0.1 days postpartum, whereas the 750 mg/kg DEHP dose delayed pubertal onset to 46.3 +/- 0.1 days postpartum. The 10 mg/kg DEHP dose also significantly increased serum testosterone (T) levels (3.13 +/- 0.37 ng/mL) and seminal vesicle weights (0.33 +/- 0.02 g) compared with control serum T (1.98 +/- 0.20 ng/mL) and seminal vesicle weight (0.26 +/- 0.02 g), while the 750 mg/kg dose decreased serum T (1.18 +/- 0.18 ng/mL) as well as testes and body weights. Direct action of the DEHP metabolite, monoethylhexylphthalate (MEHP), on Leydig cell steroidogenic capacity was investigated in vitro. MEHP treatment at a low concentration (100 microM) increased luteinizing hormone-stimulated T production, whereas 10 mM concentrations were inhibitory. In conclusion, data from the present study indicate that DEHP has a biphasic effect on Leydig cell function, with low-dose exposure advancing the onset of puberty. High doses of DEHP, which are anti-androgenic, may also be outside the range of real environmental exposure levels.     

Changes from puberty to adulthood in the concentration, motility and morphology of mouse epididymal spermatozoa

A systematic study of the concentration, motility and morphology of epididymal spermatozoa was undertaken in mice of the OF1 strain, in order to characterize the changes observed during puberty. The comparative development of these 3 parameters was followed from days 30 to 90. A detailed morphological system of classification was established covering both individual and multiple abnormalities. At puberty, the first spermatozoa to appear were few in number, showed poor motility and were extremely atypical. Subsequently, the number of atypically-shaped spermatozoa diminished, and their concentration and motility exhibited parallel increases. At 60 days, the values for these 3 parameters and the proportions of normal and abnormal spermatozoa became stable. During puberty, various forms of disruption of the midpiece as well as the presence of extremely atypical detached flagella resulted in a special pattern of sperm morphology, although all of these abnormal features disappeared at 40 days.     

Isoflavones and their effects on the onset of puberty in male Wistar rats

This study was performed to determine how two of the most important isoflavones, genistein and daidzein, affect the gonadal axis in male prepuberal rats. One hundred and seventy‐five prepuberal male Wistar rats were allocated into seven groups: one control group and six experimental groups that were orally administered a high or low dose of genistein, daidzein or a mixture of both. Testosterone determination was assayed by EIA. The testes and body weights were measured, and the histology of the epididymis with the sperm content and epididymal sperm count were evaluated. In the control group, we observed an increase in the serum testosterone levels (>2.5 ng ml^?1) at the third week (52 days), which corresponded to the onset of puberty in these rats. The same increase in serum testosterone levels was observed at the fourth week in rats that received low doses of isoflavones; therefore, we concluded that the onset of puberty was delayed. At high doses, there was no significant increase in testosterone levels, which could be related to the fact that these male rats did not reach puberty. These findings were supported by the results obtained from the analysis of the epididymal content as well as the testes/body weight ratio.     

Long-term effects of early stress due to earthquake exposure on depression symptoms in adulthood: a cross-sectional study

ObjectiveThis study aimed to investigate the long-term effects of early stress by Tangshan earthquake on symptoms of depression in adulthood.MethodA total of 1534 volunteers born and raised in Tangshan were investigated; finally, 1328 subjects were enrolled in the study. They were divided into three groups according to their birth dates: infant exposure, prenatal exposure, and non-exposure. The questionnaires and psychological evaluation of all subjects were completed using a one-on-one psychological test.ResultsThe rate of depressive symptoms in the prenatal exposure group was the highest, and the lowest in the non-exposure group, with statistical differences among the three groups (P = 0.002). Moreover, the incidences of depressed mood, suicide ideation and work and loss of interest in the prenatal exposure group were significantly higher than those in the infant exposure group and the non-exposure group (P = 0.008, P = 0.001, P = 0.038, respectively). Multiple logistic regression analysis showed that male could be a protective factor for symptoms of depression in adulthood, and earthquake exposure was an important predictor of the incidence of depression symptoms.ConclusionsFetal or infancy exposure to earthquake might correlate to depression symptoms in adulthood.     

汽车尾气来源PM2.5颗粒物长期暴露导致SD雄鼠生殖功能损害

目的:建立Sprague Dawley(SD)大鼠空气细颗粒物(PM2.5)长期暴露模型,研究PM2.5长期暴露对SD大鼠生殖功能的损伤及其机制。方法:45只SD大鼠(80~94 g,28日龄)随机分配成3组:生理盐水对照组,低剂量组[2μg/(100 g·d)],高剂量组[16μg/(100 g·d)]。每天分别给予0.9%的生理盐水或PM2.5颗粒,连续暴露60 d,最后一次暴露24 h后各实验组选取10只与正常雌鼠合笼,统计雌鼠受孕率,剩余实验鼠取材,进行精子计数和畸形率测定、睾丸组织病理学检测以及睾丸组织Connexin43蛋白表达检测。结果:与对照组雌鼠受孕率(100%)相比,PM2.5暴露组正常雌鼠受孕率(高剂量组50%,低剂量组70%)明显降低,精子数量和质量明显下降,生精小管结构紊乱,管腔精子数减少,部分次级精母细胞脱落至管腔。睾丸组织中Connexin43蛋白表达下降,血睾屏障破坏。结论:汽车尾气来源PM2.5长期暴露影响SD大鼠生殖功能。     

生命早期饥荒对成年后骨质疏松的影响

目的探讨生命早期经历饥荒对成年后骨质疏松的影响。方法采用2013年重庆某体检中心资料,选取1956年-1965年出生的3951例人员作为研究对象。将其中1956年-1958年与1963年-1965年出生人群合并作为对照组,分别比较1959年-1962年出生人群共四组与对照组在骨质疏松患病率上的差异。采用累积Logistic回归模型分析生命早期经历饥荒对成年后骨质疏松的影响。结果 1956年-1965年出生人群骨质疏松患病率为2.18%,其中对照组以及出生于1959年、1960年、1961年、1962年人群骨质疏松患病率分别为2.32%、0.84%、1.75%、3.53%、1.62%。骨质疏松患病率随年龄增长有升高趋势(Z=19.95,P0.001),且男性高于女性(Z=13.3119,P0.001)。累积Logistic回归分析显示,调整其余自变量后,生命早期经历饥荒对成年后骨质疏松有影响,与对照组相比,1960年出生人群OR值为0.712(95%CI:0.520~0.975,P=0.034),性别分层后,1960年出生男性人群OR值为0.569(95%CI:0.374~0.868,P=0.009),1961年出生男性人群OR值为1.339(95%CI:1.000~1.792,P=0.050),1960年出生女性人群OR值为1.012(95%CI:0.639~1.601,P=0.961)。结论生命早期经历饥荒对成年后骨质疏松有一定影响,主要表现在男性群体中。     

Lack of effects of prenatal exposure to lidocaine on development of behavior in rats

The objective of this investigation was to study the effects of lidocaine upon postnatal development of the rat. Lidocaine, 6 mg/kg (21 mumol/kg), was given to a group of 12 rats. Injections were administered intramuscularly, bilaterally in the masseter muscles, once a day on days 10 and 11 of pregnancy. Twelve control rats were given physiologic saline. Clinical signs, mortality, body weight, and food consumption were recorded during pregnancy and lactation. The duration of gestation was also recorded. The development of the offspring was monitored by tests of spontaneous activity, nociception, learning ability, and physical development. No clinical signs of adverse reactions were seen in any of the groups. In the majority of the learning ability tests, the control and lidocaine-treated groups showed similar results. However, in the schedule of differential reinforcement of low rates of responding (DRL 20), the lidocaine-exposed males received more reinforcements than the controls and made fewer responses. In the tests of nociception, a significant difference between sexes was recorded, in that the females were more sensitive than the males in the shock-titration test. Physical development, as monitored by swimming ability and spontaneous activity, showed no inter-group difference. The present results indicate that prenatal exposure to lidocaine fails to result in postnatal impairment of the development of behavioral performance of a wide range of tasks.     

Behavioral effects of chronic exposure to low concentrations of halothane during development in rats

Long-term behavioral effects of chronic exposure to low concentrations of halothane were evaluated in rats exposed to low (12.5 ppm) concentrations from day 2 of conception until either 30 (halothane-30) or 60 (halothane-60) days after birth. Rats similarly treated but not exposed to halothane served as controls. When these rats were tested for radial arm maze exploration as adults (1 yr old) both exposure groups showed significant deficits compared with controls. The halothane-treated rats entered significantly fewer arms before reentering an arm (entries-to-repeat). At 55 days of age, in the spontaneous alternation test, response speed was significantly slower than controls in both halothane-30 and halothane-60 rats. This effect was not seen in rats more than 55 days old. Replicating previous results, the halothane-60 rats showed deficits in learning a light-dark discrimination. This deficit was not seen with halothane-30 rats, indicating that continued halothane exposure during the 30- through 60-day period was necessary for inducing a noticeable long-term learning deficit. The results show that chronic exposure of rats to low concentrations of halothane during development results in subsequent behavioral alteration, and that termination of halothane exposure at 30 days of age rather than at 60 days of age avoids some of the signs of behavioral impairment.     

Behavioural effects of chronic exposure to sub-anesthetic concentrations of halothane, sevoflurane and desflurane in rats

BACKGROUND: A double-blind, randomized trial was conducted to determine the behavioural effects of chronic exposure to subanesthetic concentrations of halothane, sevoflurane and desflurane in rats. METHODS: Halothane, sevoflurane and desflurane group rats received 0.1%, 0.3%, and 0.6% concentrations in a flow rate of 3 L.min(-1) O(2) respectively. Control animals also received 3 L.min(-1) O(2) in another investigation room, which had the same properties as the study group rooms. Rats breathed inhaled agents or oxygen between 09:00-13:00 hr every day for 30 days. After 30 days of inhalation of subanesthetic doses of inhaled agents or oxygen, behavioural tests were applied. RESULTS: Tests of exploratory activity and curiosity (hole-board test), anxiety (elevated plus maze test) and learning and memory functions (multiple T maze test), demonstrated that chronic exposure to subanesthetic concentrations of all three anesthetics alters behavioural functions in rats. However, impairment of learning (P<0.05) and memory function (P<0.05) were greater in association with desflurane, in comparison to halothane and sevoflurane-treated rats. CONCLUSION: Chronic exposure to subanesthetic concentrations of halothane, sevoflurane and desflurane is associated with behavioural change in rats. Of the three drugs, desflurane was associated with the lowest learning and memory function test scores.     

Unilateral ureteral obstruction in neonatal rats leads to renal insufficiency in adulthood

BACKGROUND: Although unilateral ureteropelvic junction obstruction is the most common cause of congenital obstructive nephropathy in infants and children, management remains controversial, and follow-up after pyeloplasty is generally limited to the pediatric ages. We have developed a model of temporary unilateral ureteral obstruction (UUO) in the neonatal rat: One month following the relief of five-day UUO, the glomerular filtration rate (GFR) of the postobstructed kidney was normal despite a 40% reduction in the number of glomeruli and residual vascular, glomerular, tubular, and interstitial injury. METHODS: To determine whether hyperfiltration and residual injury of remaining nephrons leads to progression of renal insufficiency in later life, 31 rats were sham operated or subjected to left UUO at one day of age, with relief of UUO five days later, and were studied at one year of age. GFR was measured by inulin clearance, and the number of glomeruli, tubular atrophy, glomerular sclerosis, and interstitial fibrosis were measured by histomorphometry in sham, obstructed (UUO), and intact opposite kidneys. Intrarenal macrophages and alpha-smooth muscle actin were identified by immunohistochemistry. RESULTS: Despite relief of UUO, ultimate growth of the postobstructed kidney was impaired. The number of glomeruli was reduced by 40%, and GFR was decreased by 80%. However, despite significant compensatory growth of the opposite kidney, there was no compensatory increase in GFR, and proteinuria was increased. Moreover, glomerular sclerosis, tubular atrophy, macrophage infiltration, and interstitial fibrosis were significantly increased not only in the postobstructed kidney, but also in the opposite kidney. CONCLUSIONS: Although GFR is initially maintained following relief of five-day UUO in the neonatal rat, there is eventual profound loss of function of the postobstructed and opposite kidneys because of progressive tubulointerstitial and glomerular damage. These findings suggest that despite normal postoperative GFR in infancy, children undergoing pyeloplasty for ureteropelvic junction obstruction should be followed into adulthood. Elucidation of the cellular response to temporary UUO may lead to improved methods to assess renal growth, injury, and functional reserve in patients with congenital obstructive nephropathy.     

Comparative anti-fertility effects of gossypol enantiomers in male hamsters

The enantiomers of gossypol have been tested as male oral anti-fertility agents in hamsters. As determined by fertility tests the (-) isomer was fully active at half the effective dose of the racemate, whereas the (+) isomer exerted no anti-fertility effect.     

The effects of maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on testicular steroidogenesis in infantile male rats

Exposure of adult male animals to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) decreases serum androgen concentrations. Reduction in androgen levels after maternal exposure has also been reported, but these results have not been reproduced. We have earlier shown that TCDD stimulates rather than inhibits testosterone synthesis in the prenatal rat testis. The aim of the present study was to elucidate in utero-induced effects of TCDD on testicular steroidogenesis in the 14-day-old infant rats. At that time the foetal Leydig cell population is still the prevailing source of androgens. Pregnant Sprague-Dawley dams were given a single oral dose of TCDD (0, 0.04, 0.2, or 1.0 microg/kg) on day 13 of pregnancy. On postnatal day 14, the body weight of male offspring was reduced after exposure to 1.0 microg/kg TCDD (from 33.9 +/- 1.66 g to 31.6 +/- 2.67 g). Relative testis weight, plasma testosterone, luteinizing hormone and follicle-stimulating hormone levels remained unaltered in all exposure groups. Moreover, in ex vivo incubations, testosterone and cAMP production was not affected. StAR protein level in the freshly isolated testes was increased in the 0.2 microg/kg group, and seminiferous cord diameter in the 0.04 microg/kg group. The present study confirms our earlier findings in in utero TCDD-exposed foetal testis indicating that maternal TCDD exposure does not negatively influence the developmental testosterone production of foetal type Leydig cells in rats.     

In vitro temperature sensitivity of DNA, RNA, and protein syntheses throughout puberty in human testis.

To evaluate the optimal temperature for DNA, RNA, and protein syntheses in the prepubertal, pubertal, and postpubertal human testis, the levels of incorporation of 3H-thymidine, 14C-uridine, and 14C-leucine into cultured testicular tissue were studied at 28 degrees C, 31 degrees C, 34 degrees C, 37 degrees C, 40 degrees C, and 43 degrees C. The maximum level of 3H-thymidine incorporation in prepubertal testes occurred at 37 degrees C, whereas the maximum incorporation in the pubertal and postpubertal testes occurred at 31 degrees C. Incorporations of 14C-uridine and 14C-leucine in the three groups were temperature dependent (28 degrees C to 37 degrees C). DNA synthesis by germ cells in the pubertal and postpubertal testes was maximum at 31 degrees C and was impaired at body temperature (37 degrees C), whereas in the prepubertal testis it was temperature dependent with a maximum at 37 degrees C. RNA and protein synthesis in the three groups was temperature dependent at 28 degrees C to 37 degrees C, was depressed at 40 degrees C, and remarkably depressed at 43 degrees C.     

Long-term effects of intrauterine exposure to mono-n-butyl phthalate on the reproductive function of postnatal rats

Purpose

Although it is well known that phthalate esters induce testicular dysfunction in both adult and immature rats, there have been few reports on the long-term effect of phthalate esters on the testicular function of male rats exposed to phthalate esters in utero. This study was designed to assess the long-term effects of the mono-n-butyl phthalate (MBP) ester on the testicular function of neonatal and adult rat offspring from pregnant dams exposed to phthalate esters during gestation.

Methods

Pregnant rats were administered MBP [0.5 g/(kg body weight/·d); 4 days] by gavage from the 15th to the 18th gestational day. Rats administered solvent only were used as control subjects. After the rats' puberty, using male pups whose testes descended normally, the authors examined their fertility while also measuring their testicular weights, mean seminiferous tubular diameter, and the developmental grade of the germ cells (Johnsen score) in their testes. Next, in neonatal rats, the authors measured the testicular concentration of the Mullerian inhibiting substance (MIS) protein using enzyme-linked immunoassay and the expression level of the MIS messenger RNA using the quantitative polymerase chain reaction method as a marker of the Sertoli cells' function. Next the concentration of testosterone protein using a radioimmunoassay as a marker of the Leydig cells' function was measured.

Results

The pregnancy rate of the female rats coupled with MBP-treated male rats decreased significantly in comparison with that of the female rats coupled with control male rats (P < .01). Both the testicular weight and the Johnsen score in the MBP-treated group were decreased significantly more than those of the control group (P < .05). Neither the concentration of the MIS protein nor the expression level of the MIS messenger RNA in the MBP-treated neonatal testes differed from those of the control testes, whereas the concentration of testosterone protein in the neonate testes decreased significantly in the MBP-treated group in comparison with that of the control group (P < .01).

Conclusions

A prenatal short-time exposure to MBP induces a long-term effect on postnatal rats and impairs reproductive function in male offspring probably by inhibiting the Leydig cells' rather than Sertoli cells' function in the fetal period.     

七氟醚单次和多次暴露对新生鼠海马神经元结构的影响

目的探讨等同时间不同次数七氟醚暴露对新生大鼠海马CA1细胞形态及超微结构的影响。方法出生7d的SD雄性大鼠45只,体重14~18g,随机均分为三组:对照组(C组)、单次七氟醚暴露组(SS组)和多次七氟醚暴露组(TS组)。SS组于出生后第7天吸入1次3%七氟醚6h;TS组于出生后第7、8、9天每天吸入1次3%七氟醚2h,累计6h;C组在相应日龄吸入60%氧气。三组于出生后第14天灌注取脑,采用HE和尼氏染色观察大鼠海马CA1区锥体神经元形态及数量变化;同时,透射电镜下观察该区域神经元超微结构及突触后致密物厚度和活性区长度。结果 HE和尼氏染色显示:与C组比较,SS组和TS组海马CA1细胞排列稀疏,神经元数量明显减少(P0.05);与SS组比较,TS组海马CA1神经元数量明显减少(P0.05)。电镜结果显示:与C组比较,SS组和TS组海马CA1神经元亚细胞器均有不同程度的受损,突触后致密物厚度明显变薄,活性区长度明显缩短(P0.05);与SS组比较,TS组神经元亚细胞器损伤更明显,突触后致密物厚度更薄,活性区长度缩短更严重(P0.05)。结论七氟醚单次和多次暴露均会引起新生大鼠海马CA1区锥体神经元数量减少及细胞超微结构的改变,等同时间多次暴露比单次暴露对神经元形态的损伤更严重。     

Peritoneal transport after long-term exposure to Icodextrin in rats

BACKGROUND: Icodextrin, an effective osmotic substance that has been proposed as an alternative agent for peritoneal dialysis induces ultrafiltration over long dwells. This study examines the peritoneal transport after exposure to Icodextrin in rats. METHODS: Animals were divided in 4 groups and injected daily for 30 days with Icodextrin 7.5 % (n = 14), Glucose 4.25 % (n = 19) or glucose 4.25% plus Icodextrin 7.5 % (n = 13). Rats of the control group (n = 15) were not exposed. A 4-hour permeability study was performed using glucose at days 1, 30 and 60. At days 2, 31 and 61 the same animals were injected with Icodextrin. RESULTS: Slopes of effluent sodium at day 30 were significantly higher (p < 0.001) in the glucose (0.006 +/- 0.016), Icodextrin (0.013 +/- 0.014) and mixed groups (0.012 +/- 0.017) than in the control group (-0.041 +/- 0.021). Urea D/P ratio was not significantly different in the 4 groups. After 30 days, glucose effluent levels were significantly lower (p < 0.001) in the glucose (701 +/- 278 mg/dl), Icodextrin (552 +/- 209 mg/dl) and mixed groups (587 +/- 344 mg/dl) than in control rats (1519 +/- 413 mg/dl). Effluent protein (mg/l) in the mixed group (1,555 +/- 357) was significantly higher (p < 0.001) than control (376 +/- 33), glucose (1,015 +/- 232) and Icodextrin (765 +/- 75) groups at day 30. CONCLUSION: The long-term use of Icodextrin does not affect small molecule transport, but induces changes in the peritoneal protein excretion, especially when Icodextrin and glucose are injected together.     

Famine exposure in the young and the risk of type 2 diabetes in adulthood

The developmental origins hypothesis proposes that undernutrition during early development is associated with an increased type 2 diabetes risk in adulthood. We investigated the association between undernutrition during childhood and young adulthood and type 2 diabetes in adulthood. We studied 7,837 women from Prospect-EPIC (European Prospective Investigation Into Cancer and Nutrition) who were exposed to the 1944-1945 Dutch famine when they were between age 0 and 21 years. We used Cox proportional hazards regression models to explore the effect of famine on the risk of subsequent type 2 diabetes in adulthood. We adjusted for potential confounders, including age at famine exposure, smoking, and level of education. Self-reported famine exposure during childhood and young adulthood was associated with an increased type 2 diabetes risk in a dose-dependent manner. In those who reported moderate famine exposure, the age-adjusted type 2 diabetes hazard ratio (HR) was 1.36 (95% CI [1.09-1.70]); in those who reported severe famine exposure, the age-adjusted HR was 1.64 (1.26-2.14) relative to unexposed women. These effects did not change after adjustment for confounders. This study provides the first direct evidence, using individual famine exposure data, that a short period of moderate or severe undernutrition during postnatal development increases type 2 diabetes risk in adulthood.     

The correlation between the gossypol contents in blood plasma, rete testis fluid, and cauda epididymal fluid following chronic treatment with gossypol in rats

Concentrations of gossypol in blood plasma, rete testis fluid, and fluid from the caudia epididymidis were measured simultaneously by high performance liquid chromatography in rats treated with gossypol (15 mg/kg daily for 3 weeks). Antispermatogenic effects were demonstrated by loss of sperm motility in the cauda epididymidis and structural changes in the testis. It was found in these treated rats that concentrations of gossypol were lower in rete testis fluid compared with blood plasma but increased significantly in fluid from the cauda epididymidis. The results indicate a restriction of the blood-testis barrier to gossypol and its local concentration in the epididymis after fluid resorption.     

Long-term results of correction of tetralogy of Fallot in adulthood.

OBJECTIVES: The natural history of tetralogy of Fallot (TOF) allows that a minority of patients reach adulthood without any treatment, representing mild forms of the disease. The aim of this study is the long-term evaluation of patients with TOF surgically treated in adulthood, in order to define its real benefit. METHODS: Between November 1982 and January 2001, 39 patients older than 18 years of age with tetralogy of Fallot underwent total correction. Mean age was 26.6 years (range 18-67) and 21 patients (53.8%) were females. A previous modified Blalock-Taussig shunt was performed in four patients (10.3%). Fifteen patients (38.5%) were in NYHA functional class III or IV. Mean hematocrit was 53.6+/-10% and the mean gradient across the right-ventricular outflow tract was 93.9+/-24.8 mmHg. The operation was performed via transatrial/transpulmonary approach in 16 patients (41%) and six patients (15.4%) required transannular patch. Pulmonary valvotomy was necessary in 13 patients (33.3%) and pulmonary valve replacement with bioprosthesis in 3 patients (7.7%). RESULTS: Hospital and late mortality were 5.1 and 7.7%, respectively. The mean follow-up was 45.1 months (range 1-194 months). Actuarial survival was 91.2+/-4.9%, 85.5+/-7.2% and 68.4+/-16.3% at 3, 7 and 15 years, respectively. In the latest follow-up, 27 (79.4%) of the survivals are presently in NYHA functional class I (P<0.001). Echocardiography has shown moderate/severe pulmonary insufficiency in 9 patients (26.5%), moderate pulmonary stenosis in 3 patients (8.8%) and residual ventricular septal defect in 4 patients (11.8%). Arrhythmias were identified in 38.9% of patients with symptoms suspicious of rhythm disturbances. There was impairment of right-ventricular function in 13 patients (38.2%). Three patients were reoperated on to close residual ventricular septal defects in two patients and for pulmonary valve replacement in one patient. CONCLUSIONS: The overall survival of surgically treated adult patients with TOF is acceptable. The great benefit of the complete repair at this age is the functional improvement. On the other hand, late complications closely related to chronic hypoxia, such as arrhythmia and ventricular dysfunction might direct for a more careful follow-up after the surgical correction.