Evolving perspectives on the concept of dose in radiobiology and radiation protection

Since the discovery of the x ray more than 90 y ago, the biological effects of radiation have been a subject of intensive and continuing study. At the outset, such study was severely hampered by the lack of a suitable method of dosimetry. More than a quarter of a century elapsed before the introduction of a quantitative system for measuring exposure, and another quarter of a century elapsed before the introduction of quantitative units of absorbed dose. In the meantime, the effects of a given dose had long since been found to depend on its distribution in space and time; that is, on the precise spatial and temporal patterns of energy deposition within absorbing tissues and cells. Study of the biological effects of radiation thus led to elaboration of the concept of dose, to take into account relevant microdosimetric parameters. Advances in ongoing research on the molecular mechanisms of radiation effects can be expected to result in further evolution of such coNcepts.     

Primitive neuroectodermal tumor presenting as a delayed sequela to cranial irradiation and intrathecal methotrexate

A patient developed a primitive neuroectodermal tumor (PNET) many years after therapeutic cerebral radiation and methotrexate treatment for leukemia. The differential radiologic and histologic diagnoses, as well as the possible co-oncogenic effects of radiation and methotrexate, are evaluated.     

Urocortin interaction with corticotropin-releasing factor (CRF) binding protein (CRF-BP) : a novel mechanism for elevating ‘free’ CRF levels in human brain

Here we demonstrate that urocortin, a new mammalian member of the corticotropin-releasing factor (CRF) neuropeptide family has high affinity for both the recombinant human CRF binding protein (CRF-BP) and for a membrane-associated form of the protein solubilized from postmortem human cerebrocortical brain tissue. The rank order of binding potency for both the human recombinant CRF-BP and for the solubilized human brain CRF-BP is: urotensin > hCRF > urocortin > sauvagine. The bound hCRF/hCRF-BP complex was detected in the postmortem human brain tissue using an ELISA assay specific for the hCRF/hCRF-BP complex. A large proportion (65%) of the endogenous hCRF was found to be complexed to the CRF-BP and thus unavailable for CRF receptor activation. Incubation of human brain postmortem tissue extracts with urocortin and urotensin resulted in a dramatic decrease in hCRF/hCRF-BP levels and a concomitant increase in ‘free’ hCRF levels. Thus, urocortin and other putative CRF-related peptides may elevate endogenous levels of ‘free’ hCRF in brain by displacing hCRF from the binding protein. These data define an indirect endogenous mechanism for activation of CRF receptors by new mammalian members of the CRF family of neuropeptides.     

Symptoms versus objective rhythm monitoring in patients with paroxysmal atrial fibrillation undergoing pulmonary vein isolation

BACKGROUND: Pulmonary vein (PV) ablation is a treatment option for patients with atrial fibrillation (AF). The efficacy of treatment is often assessed by the evaluation of symptoms. However, a high proportion of AF episodes occur in the absence of symptoms as observed in pharmacological treated patients. The purpose of this study was to assess the association of symptoms and AF in patients who underwent PV ablation for the treatment of paroxysmal AF. METHODS: All consecutive patients scheduled for PV ablation received an event recorder 1 month prior to the ablation for the period of 4 months. Event strips were sent by telephone on a daily basis, and in case the patient suffered palpitations or other symptoms believed to be related to the arrhythmia. RESULTS: Forty-one patients (7 females; mean age 52 years (range 24 to 71 years)) sent a total of 3,046 event strips (735 before ablation; 2,311 after ablation). Before ablation, a total amount of 244 event strips were obtained of which were 85 (35%) were asymptomatic. After ablation, a total amount of 254 AF event strips were obtained of which 164 were asymptomatic (65%). Correlation between symptoms and rhythm was often absent during AF. CONCLUSION: Our data demonstrate that for the evaluation of effectiveness of PV ablation, the lack of symptoms during follow-up is not a valid indication. Objective rhythm monitoring in order to detect asymptomatic AF should be performed.