Impact of a novel family-centered values clarification tool on adolescent sperm banking attempts at the time of a new cancer diagnosis

Purpose

Over half of males experience fertility impairment after childhood cancer therapy, which often causes psychosocial distress. Yet, fertility preservation (FP) remains underutilized. The goals of this study were to determine the feasibility and impact of implementing a family-centered FP values clarification tool on sperm banking attempts among adolescent males newly diagnosed with cancer, and identify key determinants of banking attempts.

Methods

A prospective pilot study was conducted among families of males (12–25 years old), prior to cancer therapy. Thirty-nine of 41 families agreed to participate (95%); 98 participants (32 adolescents, 37 mothers, 29 fathers) completed the Family-centered Adolescent Sperm banking values clarification Tool (FAST). Analyses assessed the impact of the FAST on banking attempts and examined associations between demographic/medical characteristics, FAST subscales (perceived threat, benefits, barriers), and banking attempts.

Results

Twenty-three (59%) adolescents attempted to bank, compared to 8 adolescents (33%) during baseline assessment (p=.04). Significant associations were identified between banking attempts and adolescents’ report of perceived threat (r_pb=.45, p=.01) and benefits (r_pb=.57, p=.01). Only mothers’ proxy reports of adolescent perceived threat (r_pb=.42, p=.01) and benefits (r_pb=.47, p=.003) were associated with banking attempts, while fathers’ self-reported perceived benefits (r_pb=.43, p=.03), self-reported barriers (r_pb=.49, p=.01), and proxy reports of adolescent perceived threat (r_pb=.38, p=.04) and benefits (r_pb=.59, p=.02) were associated with banking attempts.

Conclusion

Adolescent sperm banking attempt rates significantly increased after implementation of a family-centered FP values clarification tool prior to cancer treatment. Findings underscore the importance of targeting both adolescents and their parents, particularly fathers, in FP efforts.

     

Evaluation of STOX1 as a preeclampsia candidate gene in a population-wide sample

Preeclampsia is a common, pregnancy-specific vascular disorder characterised by hypertension and proteinuria. A recent report suggested association of the STOX1 gene on chromosome 10q22.1 with preeclampsia in the Dutch population. Here, we present a comprehensive assessment of STOX1 as a candidate gene for preeclampsia in the Finnish population by re-examining our previous genetic linkage analysis results for both chromosome 10 and paralogous loci, by genotyping representative markers in a nationwide data set, and by studying STOX1 expression in placentas from preeclamptic and uncomplicated pregnancies. In conclusion, we are unable to validate STOX1 as a common preeclampsia susceptibility gene.     

In vitro electroretinogram for the study of the functionality of differentiated retinal pigment epithelium cells

The purpose of this study is to develop and test a method to reveal if the retinal pigment epithelium (RPE) cells differentiated from human embryonic stem cells (hESC) support the functions of photoreceptors. hESC-derived RPE (hESC–RPE) cells offer a potent cell source for cell replacement therapy that may be used to prevent certain eye diseases. Methods to assure the functionality of the RPE cells are well warranted. Electroretinograms (ERG) measure the electrophysiological response of the retina to light stimuli. A setup was developed that enables the measurement of ERG in vitro from mice retinas cultured together with hESC–RPE cells. The co-culture of RPE and retinas seems to be a viable tool to assess the functionality of RPE in vitro. However, owing to limited sample size results were somewhat mixed, and thus it was not possible to prove that hESC–RPE cells enhance the ERG response of a mouse retina in vitro. The long-term culturing of the retinas needs to be refined to acquire more conclusive evidence of the supporting role of the RPE and to explore the full potential of the co-culture and ERG methods in assessing RPE functionality.     

Chromosomal aberrations in railroad transit workers: Effect of genetic polymorphisms

Complex chemical mixtures are transported by train from Russia to Finland for further shipment. Here, we studied if exposure to genotoxic components among these substances could affect chromosomal aberrations (CAs) in peripheral lymphocytes of workers handling the tank cars. An initial survey among 48 railroad workers and 39 referents (male smokers and nonsmokers) showed an elevation of CAs. A campaign was started to reduce exposures through preventive measures. Five years later, 51 tank car workers and 40 age‐matched referents (all nonsmoking men) were studied for CAs and genetic polymorphisms of xenobiotic metabolism (EPHX1, GSTM1, GSTP1, GSTT1, NAT1, NAT2), DNA repair (ERCC2, ERCC5, XPA, XPC, XRCC1, XRCC3), and folate metabolism (MTHFR, MTR). No increase in CAs was seen in the exposed group, suggesting that the preventive measures had been successful. However, a positive association existed between exposure duration and CA level among the exposed subjects. The level of chromosome‐type breaks was actually lower in the exposed workers than the referents, particularly among MTHFR wild‐type homozygotes or XRCC3 codon 241 variant allele carriers, suggesting modulation of CA frequency by folate metabolism and DNA repair. An interaction was observed between the occupational exposure and MTHFR, EPHX1, and MTR genotypes in determining CA level. The NAT2, ERCC2 exon 10, and XRCC1 codon 194 polymorphisms also affected CA frequency. Our findings suggest that handling of tank cars containing complex chemical mixtures poses a genotoxic risk, which may be reduced by preventive measures. Several genetic polymorphisms seem to modify the genotoxic effect or baseline CA level. Environ. Mal. Mutagen. 2009. © 2009 Wiley‐Liss, Inc.     

Imaging and spectroscopic findings in meningioangiomatosis

Meningioangiomatosis (MA) is an uncommon brain tumor. The role of imaging techniques is underscored in cases where the tumor location makes resection (or even biopsy) dangerous. We report the case of a child with an MA tumor located deep in the right sylvian fissure. A computed tomography (CT) scan showed calcifications in a highly vascular lesion with surrounding edema. Magnetic resonance spectroscopy (MRS) showed a distinct choline (Cho) peak, which usually suggests a proliferating tumor. Fluorodeoxyglucose positron emission tomography (FDG‐PET) showed the lesion lacked hypermetabolic features. These radiological features should put MA in the differential diagnosis. Pediatr Blood Cancer 2009;53:672–674. © 2009 Wiley‐Liss, Inc.     

Prognostic Studies in Breast Cancer: Multivariate combination of nodal status, proliferation index, tumor size, and DNA ploidy

We studied histological samples and clinical data from 111 breast carcinoma patients originally treated in 1975-1977 who did not have distant metastases at the time of diagnosis. A multivariate survival analysis using the Cox model selected the studied variables in the following order according to their prognostic association (breast cancer deaths, or deaths from any cause): axillary lymph node status, tumor size, mitotic index, and DNA ploidy status. The association of the different variables to the prognosis in respect to breast cancer deaths was evaluated 1-10 years after treatment by stepwise logistic regression. Lymph node status, tumor size, mitotic index, and DNA ploidy all showed significant relation to the prognosis but this association varied considerably with time of observation.     

Effect of concomitant hormone replacement therapy containing estradiol and levonorgestrel on the pharmacokinetics of selegiline

OBJECTIVE: The aim of this study was to investigate the effect of hormone-replacement therapy (HRT) on the pharmacokinetics of the selective monoamine oxidase B inhibitor selegiline and its primary metabolites desmethylselegiline and l-metamphetamine. METHODS: In this randomised, double-blind, cross-over trial, 12 healthy female subjects received once daily for 10 days either HRT containing 2 mg estradiol valerate and 250 microg levonorgestrel or matched placebo. On day 10, they took a single 10-mg oral dose of selegiline. The serum concentrations of selegiline, desmethylselegiline and metamphetamine were measured for 32 h. RESULTS: There was a 59% difference ( P=0.14) in the area under the serum concentration-time curve (AUC) of selegiline during the HRT compared with the placebo phase, but only a little or no concomitant reduction in the AUC of desmethylselegiline (-7%, P=0.071) or metamphetamine (2%, P=0.614) was observed. Maximum plasma concentration (C(max)) of selegiline was not changed, but a small, statistically significant, reduction in the C(max) of desmethylselegiline (-17%, P=0.03) was seen during the HRT phase. The C(max) of methamphetamine was slightly but not significantly reduced (-5%, P=0.06). The unchanged AUC ratios of desmethylselegiline/selegiline and metamphetamine/selegiline indicate that the primary metabolism of selegiline was not affected by HRT. All study treatments were well tolerated. CONCLUSION: Unlike oral contraceptives, HRT is not likely to have clinically significant pharmacokinetic interaction with selegiline.