Late Protective Effects of the Anticalmodulin Drug Fluphenazine on Carbon Tetrachloride-induced Liver Necrosis

Fluphenazine (FP) treatment (50mg/kg bw, ip in saline) 30 min before or 6 or 10 h after CCl4 administration (1 ml/kg ip in olive oil) significantly prevented the liver necrosis produced by the hepatotoxin at 24 h. FP had enhancing effects on the covalent binding of CCl4 reactive metabolites to cellular constituents and on CCl4 induced lipid peroaldation.FP lowered bOdy temperature of the CCl4-poisoned animals during the 24 h observation period. The obtained results are compatible but do not prove the hypothesis that calmodulin (CaM) had participation in late occurring events preceding necrosis. FP lowering action on body temperature, however, might also play a role in the effects of this drug on the onset of CCl4 induced liver necrosis. FP levels in liver tissue as determined by gas chromatography-mass spectrometry evidenced the presence of the drug in amounts suffi cient to inhibit CaM and that suggests that not all preventive effects of FP are due to its indirect actions on the central nervous system via decreased body temperature

Cancer Survivors’ Experience of Health-Related Quality of Life Six to Eight Years after Diagnosis—A Qualitative Study

Background: Health-related quality of life (HRQOL) is affected for many years following cancer treatment. With an increasing number of long-term cancer survivors, HRQOL will be a key concern in the future. There is a lack of qualitative studies investigating long-term cancer survivors’ needs and experience of late effects and HRQOL. Objective: The aim of this sub-study is to describe cancer survivors’ own experience of late effects affecting HRQOL six to eight years after diagnosis. Methods: We used a qualitative methodology with semi-structured focus group interviews to gain an in-depth understanding of participants’ experience of their HRQOL. Interviews were audio-recorded, transcribed and analyzed using thematic analysis. Results: All of the participants reported late effects at some point after the treatment. Some of the experienced late effects had improved over the years, while the late effects mentioned in this article were still prominent six to eight years after the diagnosis. They described, among others, late effects such as reduced physical strength, cognitive difficulties, lack of energy and increased sensitivity. The participants described the late effects as bearable, but still affecting their HRQOL by limiting their activity level, their ability to work and their social interactions. Conclusions: Six to eight years post-treatment, cancer survivors still experienced physical and cognitive late effects affecting their HRQOL. The findings indicate that some late effects affect HRQOL for a long time. To prepare cancer survivors for post-treatment life and to optimize their HRQOL, they need information concerning potential late effects before, during and after cancer treatment, as well as support services and follow-up in the municipalities.

Long-term results of suppressing thyroid-stimulating hormone during radiotherapy to prevent primary hypothyroidism in medulloblastoma/PNET and Hodgkin lymphoma:a prospective cohort study

Primary hypothyroidism commonly occurs after radiotherapy(RT),and coincides with increased circulating thyroid-stimulating hormone(TSH)levels.We tested therefore the protective effect of suppressing TSH with L-thyroxine during RT for medulloblastoma/PNET and Hodgkin lymphoma(HL)in a prospective cohort study.From 1998 to 2001,a total of 37 euthyroid children with medulloblastoma/PNET plus 14 with HL,scheduled for craniospinal irradiation and mediastinum/neck radiotherapy,respectively,underwent thyroid ultrasound and free triiodothyronine(FT3),free thyroxine(FT4),and TSH evaluation at the beginning and end of craniospinal iiradiation.From 14 days before and up to the end of radiotherapy,patients were administered L-thyroxine checking every 3 days TSH to ensure a value<0.3μIU/mL.During follow-up,blood tests and ultrasound were repeated;primary hypothyroidism was considered an increased TSH level greater than normal range.Twenty-two/37 patients with medulloblastoma/PNET and all the 14 patients with HL were alive after a median 231 months from radiotherapy with 7/22 and 8/14 having correctly reached TSH levels˂0.3μIU/mL and well matched for other variables.Twenty years on,hypothyroidism-free survival rates differed significantly,being 60%±15%and 15.6%±8.2%in TSH-suppressed vs.not-TSH suppressed patients,respectively(P=0.001).These findings suggest that hypothyroidism could be durably prevented in two populations at risk of late RT sequelae,but it should be confirmed in a larger cohort.

Follow-up of two victims of a 60Co-source radiation accident in 1986, Kaifeng, Henan Province, China

Objective:To explore the late effects of acute radiation exposure through the follow-up of two victims of a 60Cosource radiation accident,who suffered moderate acute radiation sickness of bone marrow type.Methods:On May 26,1986,a power failure occurred suddenly at an irradiation plant in Kaifeng,Henan Province,China,during which two workers at the site,named Liang and Yan,accidentally entered the 60Co-source irradiation cell in service.Long-term medical observations were carried out on them following the accident.Results:The late effects of the accident on Liang and Yan were observed.The main manifestations of Liang were hypomnesia and visual impairment.A typical radiation-induced cataract developed 2 years after exposure.Local cutaneous radiation injury and resultant five operations were performed within a period of five years after exposure.The decrease in the number and low viability of his sperms was found 1 year after exposure.The decrease in his leukocytes and platelets occurred during 1–5 years after exposure.He died from intrahepatic cholangiocarcinoma 21 years after exposure.For Yan,the main manifestations included headache,dizziness,fatigue,insomnia,and susceptibility to cold just after exposure.She had intermittent menolipsis at age 41.The leukocytes was fluctuating in the range of(3.1–3.9)109/L 14–24 years after exposure.A decrease in estradiol(reproductive hormone)and an increase in follicle-stimulating hormone were observed.Thyroid nodules were detected by thyroid ultrasound 21 years after exposure.She died from acute myeloid leukemia(AML)32 years after exposure.Conclusions:Follow-up of victims exposed to a high activity radiation source should focus on the organs sensitive to radiation and on the radiation-induced carcinogenesis.