Serious adverse effects of amifostine during radiotherapy in head and neck cancer patients

Background and purpose: Amifostine has been shown to protect against xerostomia induced by radiotherapy for head and neck cancer, but its impact on the therapeutic index is unknown. This is the first report focusing on amifostine related adverse effects leading to discontinuation of amifostine treatment.

Patients and methods: Thirty-nine patients from two centers irradiated for head and neck cancer received i.v.-infusions of amifostine prior to each radiation fraction. In a phase III study, two daily amifostine doses, 200 mg/m² (n=21) and 340 mg/m² (n=18), were compared for protection against radiation induced toxicity. Total radiation dose was 60–70 Gy (2 Gy per fraction), nine patients received concurrent chemotherapy with cisplatin/5-FU. amifostine was usually discontinued after >1 episode of serious toxicity during subsequent treatment sessions.

Results: In 16/39 patients (41%) amifostine was discontinued due to severe adverse effects, which led to discontinuation of the phase III study. In four of 16 patients radiotherapy was delayed due to amifostine related adverse effects for 1–3 days. Discontinuation occurred more often in patients receiving chemotherapy. The results led to a literature review for amifostine treatment during radiotherapy in head and neck cancer patients. Regarding our series and published series using an amifostine schedule comparable to ours, total discontinuation rate was 27% (57/214). Discontinuation was significantly influenced by chemotherapy (P=0.007), but not by amifostine dose (P=0.156).

Conclusion: Daily i.v. administration of amifostine during radiotherapy in head and neck cancer is associated with a high rate of serious adverse effects leading to discontinuation of amifostine treatment and sometimes delay of radiotherapy.     

GABRA2 alleles moderate the subjective effects of alcohol, which are attenuated by finasteride.

GABA(A) receptors are involved in the subjective effects of alcohol. Endogenous neuroactive steroids interact with GABA(A) receptors to mediate several behavioral effects of alcohol in rodents. Based on a haplotypic association of alcohol dependence with the gene encoding the GABA(A) receptor alpha-2 subunit (GABRA2), we examined whether GABRA2 alleles are associated with the subjective response to alcohol. We also examined whether finasteride (a 5-alpha steroid reductase inhibitor), which blocks the synthesis of some neuroactive steroids, reduces the subjective response to alcohol. In all, 27 healthy social drinkers (15 males) completed a randomized, double-blind, placebo-controlled study of high-dose finasteride. After being pretreated with study drug, subjects consumed three alcoholic drinks. Subjective effects were measured repeatedly over the ascending blood alcohol curve. To examine the moderating role of genetic variation in GABRA2, a single-nucleotide polymorphism that was informative in association studies was included as a factor in the analysis. Subjects homozygous for the more common A-allele (n=7) showed more subjective effects of alcohol than did individuals with one or two copies of the alcohol dependence-associated G-allele (n=20, including two homozygotes). Among the A-allele homozygotes, there was a greater reduction in several subjective effects during the finasteride session compared to the placebo session. These findings provide preliminary evidence that the risk of alcoholism associated with GABRA2 alleles may be related to differences in the subjective response to alcohol. The effects of finasteride provide indirect evidence for a mediating role of neuroactive steroids in some of the subjective effects of alcohol.     

Factors Affecting Utilization of Family Planning Services in a Post-Conflict Setting,South Sudan: A Qualitative Study

This study aims to explore and examine the conjectures surrounding the utilization of family planning services among currently married couples of childbearing age in Renk County.This study has adopted a qualitative method to collect data on factors affecting the utilization of family planning services through focus group discussions and in-depth interviews, in rural and urban areas of Renk County. It targeted married women, men as well as unmarried men and women. The researchers conducted nine focus group discussions and nine interviews at both Jelhak (rural setting) and Renk (urban setting). The results suggested that the people of Renk County prefer to have large families and therefore choose not to use family planning methods. The data collected was analyzed by means of thematic analysis. This included the construction of a thematic framework, coding, editing and categorization of available data as well as the creation of sub-themes.The result also suggested that perception is a main factor that affects utilization of family planning services with a majority of the people in Renk and Jelhak preferring to have many children in order to increase the family size for some reasons. These are linked to religion, social stigma and taboo that are attached to childless people or users of family planning methods for birth control purposes.The responses revealed some variation in perception between rural (Jelhak) and urban (Renk) areas. Respondents from Renk area reported that some people use family planning services for economic reasons that involve alleviation of financial difficulties and provision of better education when the family size is small. On the other hand, rural people from Jelhak perceive family planning to be socially un-acceptable. Furthermore, men and women of Jelhak reported that after each birth of a child, married couples avoid sexual relationship for a period of two years as means of family planning. Women of both Urban and Rural settings reported intentions to use conventional methods of family planning without the knowledge of their spouses.     

Nuclear and cytoplasmic features in the diagnosis of Clark's nevi

Background

Interpretation of Clark's nevi has generated debate over the years; although criteria have been proposed for grading morphological features of melanocytes, there is still confusion and variability in the assessment of these lesions.

Methods

This is a retrospective observational study conducted on 100 Clark's nevi and 84 melanomas. A single expert dermatopathologist evaluated all blinded and randomized photomicrographs of both the Clark's nevi and melanomas for the presence of 14 cytologic features. Subsequently, a multivariate model was used to obtain sensitivity and specificity.

Results

Clark's nevi showed a significantly higher frequency of absent‐or‐inconspicuous nucleoli over melanoma, whereas mitotic figures, pleomorphism, notching, multiple nucleoli, peppered moth nuclear pattern, flattened adjacent nuclei, prominent nucleoli and vesicular nucleus with rounded nucleoli were found significantly higher in frequency in melanomas.

Conclusion

Our data suggest that nuclear alterations are of value in the differentiation of atypical nevi from melanoma.