Late Effects

Many PAs and SPRMs display antiproliferative effects in the nonhuman primate endometrium where they suppress estrogen-dependent endometrial proliferation and mitotic activity, secretory activity, and reduce endometrial thickness and wet weight [31, 32]. This antiproliferative effect has been described as noncompetitive [31]. 

This effect on the AR thus appears to be the most likely mechanism explaining the antiproliferative effect although it may also be related to the fact that the PR-A isoform 

In both women and in nonhuman primates, administration of PAs or SPRMs is associated with a reduction of menstrual bleeding or even amenorrhea. This could be a consequence of this antiproliferative effect although it may also be due to direct effects on endometrial vasculature and may be independent of endometrial atrophy. Low doses of mifepristone (2 or 5 mg daily) upregulate GR in the endometrial glandular nuclei and surface (luminal) epithelium as well as reducing stromal VEGF protein expression. This may also contribute to the amenorrhea [47]. 

The PA mifepristone also delays or inhibits ovulation, which may produce amenorrhea [48, 49]. Amenorrhea may be a consequence of an effect at the level of the ovary, pituitary or hypothalamus. The SPRM asoprisnil, in contrast, is not so effective in inhibiting ovulation [50]. The amenorrhea consequent to PAs and SPRMs occurs with levels of estradiol in the range of the early follicular phase of the menstrual cycle [48-50]. As a result ofthe antiproliferative effect and the amenorrhea, PAs and SPRMs have been advocated in the treatment of uterine myoma, endometriosis and dysfunctional uterine bleeding. 

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Treatment with these doses of radiotherapy involves toxicity. Both acute and late effects of radiotherapy occur. Acute effects of mantle-field irradiation include nausea, vomiting, anorexia, xerostomia, dysguesia, pharyngitis, dry cough, fatigue, diarrhea,... 

Recognize the late effects of the treatment for long-term survivors of acute leukemias. 

Now that 80% or more of children survive their primary cancers, the incidence of secondary neoplasms may increase. Recognizing this potential, many treatment regimens for children are being modified appropriately to reduce exposure to alkylators, topoisomerase inhibitors, and radiation. Late effects clinics screen for secondary malignancies and other disease and treatment-related disabilities that accompany childhood cancer. Similar screening and educational opportunities are not currently established in adult survivors. 

Nifatov AP, Buldakov LA, Matveev VI. 1972. Some late effects after a single inhalation of 239Pu and 241Am in dogs. Health Phys 22 875. 

Late Effects (of radiation exposure)—Effects which appear 60 days or more following an acute exposure. 

Late effects Headache, fatigue, contemplative state... 

The NIOSH immediately dangerous to life and health (IDLH) value (NIOSH 1994) is greater than the 30-min AEGL-3. NIOSH based their recommended exposure limit (REL) on the statement by Flury and Zernik (1931) that 45-54 ppm could be tolerated by man for 0.5 to 1 h without immediate or late effects. Although the Flury and Zernik (1931) data are based on animal studies, NIOSH did not apply a UF. 

Electrophysiological effects Extracts of hypericum were examined for their electrophysiological effects in animals. The onset of effects occurred 3-4 hours after administration. Frequencies affected first were in the alpha range and were maximal in the frontal cortex (Dimpfel and Hofmann 1995). Another study examined the EEG effects for two hypericum extracts in rats one extract high in hyperforin and lacking naphthodi-anthrones (C02), and another extract (LI 160) low in hyperforin. Both extracts showed similar early alpha effects, but only LI 160 had a late effect of increased delta frequencies. The alpha effects are comparable to... 

Investigators have employed all schemes inducing conventional fractionation (180-200 rad/d), hyperfractionation, and hypofractionation. There is no convincing evidence that infused 5-FU affects the late effects of radiation, which are a function, primarily, of the daily treatment fraction size. However, the capacity to combine radiosensitizing infused 5-FU with hyperfractionated radiation should be considered, especially in patients requiring retreatment where tolerance is an issue and can be increased by hyperfractionation. 

Baxter PJ, Langlands AO, Anthony PP, et al. 1980b. Angiosarcoma of the liver A marker tumour for the late effects of Thorotrast in Great Britain. Br J Cancer 41 446-453. 

Guimaraes JP, Lamerton LF. 1956. Further experimental observations on the late effects of Thorotrast administration. Br J Cancer 10 527. 

Muller WA, Gdssner W, Hug 0, et al. 1978. Late effects after incorporation of the short-lived alpha-emitters radium-224 and thorium-227 in mice. Health Phys 35 33-55. 

Stougaard M, Praestholm J. Stoier M. 1984. Late effects of perivascular injection of Thorotrast in the neck. J Laryngol Otol 98 1003-1007. 

Wegener K, Wesch H, Kampmann H. 1976. Investigations into human Thorotrastosis tissue concentrations of thorium-232 and late effects in 13 autopsy cases. Virchows Arch Path Anat Histol 371 131-143. 

Van der Pol, M.C., Hadders-Algra, M,. Huisjes, H.J., and Touwen, B.C. (1991) Antiepileptic medicaton in pregnacy late effects on the children s central nervous system development. Am J Obstet Gynecol 164 121-128. 

The RBE values for late effects are significantly higher than for early effects (Figs. 4 and 5). 

Sasaki, S., Tsutomu, K., Sato, R, and Kawashima, N. (1978). Late effects of fetal mice irradiated at middle or late uterine stage, Gann 609,167. 

Hahn, P. and Kirby, L. 1973. Immediate and late effects of premature weaning and of feeding a high fat or high carbohydrate diet to weanling rats. J. Nutr. 103, 690-696. 

There is a vast literature on the response of cellular systems, from bacteria to mammalian cells, but also animal and even clinical studies. In the present context, the emphasis will be on mechanistic details concerning the free-radical aspects. The most important late effects, notably the processing of DNA damage by the repair enzymes cannot be dealt with here. 

Kofranek, V, Sedlak A, Bubenikova D, et al. 1985. Late effects of 226Ra, 224Ra and 239Pu in female mice of the ICR strain. Strahlentherapie [Sonderb] 80 88- 92. 

Looney WB. 1955. Late effects (twenty-five to forty years) of the early medical and industrial use of radioactive material Their relation to the more accurate establishment of maximum permissible amounts of radioactive elements in the body. Part I. J Bone Joint Surg [Am] 37-A 1169-1187. 

Wick RR, Gossner W. 1983. Follow-up study of late effects in Ra treated ankylosing spondylitis patients. Health Phys 44 187-195. 

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