The ultrastructure of optic nerve axons was examined in several mammals (human, cat, rat, sheep, ox, pig, guinea pig, rabbit). Human material was obtained from normotensive, glaucoma-free eyes and from eyes with a history of glaucoma and raised intra-ocular pressure (IOP). We describe accumulations of organelles (principally mitochondria) in optic nerve axons where they traverse the lamina cribrosa. Accumulations were most prominent in unmyelinated lengths of axons close to lamellae of the lamina cribrosa. Comparable accumulations were not apparent in axons in the retina or optic nerve, suggesting that axoplasmic flow is constricted at the lamina cribrosa. Accumulations were observed both centrally and peripherally to the lamellae, suggesting that flow is constricted in both ortho- and antero-grade directions. Accumulations of organelles were more marked in unmyelinated axons than in adjacent, myelinated axons. In the rabbit, in which most axons are myelinated as they traverse the optic nerve head, organelle accumulations were observed only in a sparse population of unmyelinated axons. In human eyes with a history of raised IOP and glaucoma, the accumulations were abnormally large and frequent and in many axons showed dense-body and fibrillar changes not seen in normotensive eyes. It is suggested that chronic, partial constriction of axoplasmic flow is present at the lamina cribrosa of normotensive eyes in a wide range of mammals, including humans, that the constriction results from the pressure gradient across the lamina cribrosa and that the constriction may be a factor in the many cases of primary glaucoma in which IOP is not raised.
The Chernobyl nuclear power plant accident on April 26, 1986 was the largest in the history of the peaceful use of nuclear energy. Of the 237 individuals initially suspected to have been significantly exposed to radiation during or in the immediate aftermath of the accident, the diagnosis of acute radiation sickness (ARS) could be confirmed in 134 cases on the basis of clinical symptoms. Of these, 54 patients suffered from cutaneous radiation syndrome (CRS) to varying degrees. Among the 28 patients who died from the immediate consequences of accidental radiation exposure, acute hemopoietic syndrome due to bone marrow failure was the primary cause of death only in a minority. In 16 of these 28 deaths, the primary cause was attributed to CRS. This report describes the characteristic cutaneous sequelae as well as associated clinical symptoms and diseases of 15 survivors of the Chernobyl accident with severe localized exposure who were systematically followed up by our groups between 1991 and 2000. All patients presented with CRS of varying severity, showing xerosis, cutaneous telangiectasias and subungual splinter hemorrhages, hemangiomas and lymphangiomas, epidermal atrophy, disseminated keratoses, extensive dermal and subcutaneous fibrosis with partial ulcerations, and pigmentary changes including radiation lentigo. Surprisingly, no cutaneous malignancies have been detected so far in those areas that received large radiation exposures and that developed keratoses; however, two patients first presented in 1999 with basal cell carcinomas on the nape of the neck and the right lower eyelid, areas that received lower exposures. During the follow-up period, two patients were lost due to death from myelodysplastic syndrome in 1995 and acute myelogenous leukemia in 1998, respectively. Other radiation-induced diseases such as dry eye syndrome (3/15), radiation cataract (5/15), xerostomia (4/15) and increased FSH levels (7/15) indicating impaired fertility were also documented. This study, which analyzes 14 years in the clinical course of a cohort of patients with a unique exposure pattern, corroborates the requirement for long-term, if not life-long, follow-up not only in atomic bomb survivors, but also after predominantly local radiation exposure.
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