Mutational Analysis of Androgen Receptor (AR) Gene in 46,XY Patients with Ambiguous Genitalia and Normal Testosterone Secretion: Endocrinological Characteristics of Three Patients with AR Gene Mutations

The prevalence of abnormalities in androgen receptor gene (AR) among patients with ambiguous genitalia is unknown. Moreover, endocrinological data from prepubertal patients with AR mutation are very limited. Thus, the aim of this study was to examine the prevalence of abnormalities in AR among patients with both ambiguous genitalia, which was defined as a combination of two or more genital abnormalities (i.e. hypospadias, microphallus (penile length < 25 mm), hypoplastic scrotum, bifid scrotum, undescended testis) in this study, and normal to elevated T levels. We also compared the endocrinological data of prepubertal patients with AR mutation and ambiguous genitalia with that of those without the AR mutation. We screened 26 Japanese prepubertal 46,XY patients (five from three families were included) with both ambiguous genitalia and normal to elevated T levels. Mutations in AR were found in three (two of the three were related). Among the 23 patients without mutation in AR, the steroid 5-alpha-reductase 2 gene (SRD5A2) was also examined in eight patients with elevated T/dehydrotestosterone ratio after the hCG (>10) or with undervirilized family members. No mutation in SRD5A2 was found. Characteristics of the three patients with mutation in AR were compared with the 23 patients without mutation. In two patients, basal T levels (0.3, 0.2 ng/ml) and peak T levels after the hCG tests (8.3, 8.5 ng/ml) tended to be higher, and the peak LH/ peak FSH ratios after the GnRH tests (4.6, 4.0) were higher than in patients without mutation, at the ages of 1 yr and 9 mo and 3 yr and 8 mo, respectively. In conclusion, an abnormality in either AR or SRD5A2 was not common among patients with ambiguous genitalia and normal testosterone secretion. Elevated peak LH/peak FSH ratio (≥4) after the GnRH test in addition to detectable basal T levels and elevated peak T levels after the hCG test may infer AR abnormality in prepubertal patients with ambiguous genitalia at the age of one and over, although further study is needed, because our data were limited.     

Radiotherapy plus cetuximab for locally advanced squamous cell head and neck cancer in patients with cisplatin-ineligible renal dysfunction: A retrospective study

Clinical trials have not fully demonstrated the efficacy and safety of radiotherapy plus cetuximab for locally advanced squamous cell head and neck cancer (LA-SCCHN) in patients with cisplatin-ineligible renal dysfunction. Patients who received radiotherapy plus cetuximab for LA-SCCHN at Chiba University Hospital (Chiba, Japan) between July 2013 and October 2018 were retrospectively reviewed. Background characteristics and locoregional control and overall survival rates were compared between patients with and without renal dysfunction. Survival was examined using Kaplan-Meier analysis and an adjusted Cox proportional hazards model. Kaplan-Meier analysis demonstrated that overall survival was shorter in patients with creatinine clearance of <45 ml/min (P=0.041; log-rank test). However, there was no difference in the locoregional control rate (P=0.477; log-rank test). Adjusted Cox analysis revealed that the risk of death was increased by 2.52-fold (hazard ratio, 2.52; 95% confidence interval, 1.01-6.30; P=0.048) if creatinine clearance was <45 ml/min. Moderate to severe renal dysfunction did not affect the locoregional control rate in patients with LA-SCCHN treated with radiotherapy plus cetuximab but was an adverse prognostic factor.     

PAX5 alterations in an infant case of KMT2A‐rearranged leukemia with lineage switch

Lineage switch is a rare event at leukemic relapse. While mostly known to occur in KMT2A‐rearranged infant leukemia, the underlying mechanism is yet to be depicted. This case report describes a female infant who achieved remission of KMT2A‐MLLT3‐rearranged acute monocytic leukemia, but 6 months thereafter, relapsed as KMT2A‐MLLT3‐rearranged acute lymphocytic leukemia. Whole exome sequencing of the bone marrow obtained pre‐post lineage switch revealed two somatic mutations of PAX5 in the relapse sample. These two PAX5 alterations were suggested to be loss of function, thus to have played the driver role in the lineage switch from acute monocytic leukemia to acute lymphocytic leukemia.     

Antitumor activity of dextran derivatives immobilizing platinum complex (II)

The in vivo antitumor activity and toxicity of a newly synthesized polymeric prodrug of cisplatin was investigated and also compared with plain cisplatin. The prodrug included a dicarboxymethyl-dextran conjugate of cisplatin (DCM-Dex/CDDP). DCM-Dex/CDDP was i.v. injected in mice bearing s.c. Colon 26 mouse colon cancer cells. The tissue distribution of platinum was thereafter determined by flameless atomic absorption spectrophotometry. The platinic concentration of the organs showed a high rate of retention at 24 h after injection in the DCM-Dex/CDDP-treated mice. No biochemical or hematologically adverse effects were observed. In addition, DCM-Dex/CDDP showed a significantly higher antitumor activity than cisplatin alone. These results indicate that DCM-Dex/CDDP may therefore be a potentially effective cancer chemotherapy.     

Fast magnetic resonance imaging of liver.

Recent magnetic resonance (MR) units with a stronger gradient system have allowed various fast MR imaging techniques to develop. These fast scan techniques have easily realized breath-holding acquisition in the liver and the image quality has been greatly improved without sacrificing spatial resolution. The majority of the fast imaging techniques have been devoted to T2-weighted imaging to obtain useful T2-weighted images in the shortest possible time. Among the fast sequences, fast spin-echo (FSE) sequence is the most promising technique and allows high-quality T2-weighted images with reduced motion artifacts. However, FSE sequences using multiple refocused pulses may essentially realize only poor soft-tissue contrast due to magnetization transfer and T2-filtering effects, and therefore, echo-planar (EP) imaging is expected to provide high image contrast. In addition, single-shot EP imaging allows even diffusion-weighted (DW) and perfusion-weighted (PW) imaging in the liver due to its short scanning time. Recent development of fast gadolinium-enhanced 3D MR angiography has also impacted liver imaging. Combined with such gadolinium-enhanced 3D-MRA sequences and zerofilling image interpolation technique, biphasic gadolinium-enhanced 3D-MRA (whole-liver dynamic MR imaging in the arterial phase and MR portography in the portal phase) can be obtained.     

An Analytical Model / Emotional Intelligence Quotient and QOL in Mothers with Infants in Japan

Objective: The purpose of this study was to examine the relationship betweenthe emotional intelligence quotient and health-related quality of life using structuralequation modeling.Methods: A self-administered questionnaire survey was conducted among 1,911mothers who visited the Health Center for an infant medical examination. A hypotheticalmodel was constructed using variables of the emotional intelligence quotient, socialsupport, coping, parenting stress, and perceived health competence.Result: There were a total of 1,104 valid responses (57.8%). Significantstandardized estimates were obtained, confirming the goodness of fit issues with themodel. The emotional intelligence quotient had a strong impact on physical andpsychological quality of life, and showed the greatest association with coping. This studydiffered from previous studies in that, due to the inclusion of social support andexplanatory variables in coping, an increase in coping strategies was more highlyassociated with emotional intelligence quotient levels than with social support.Conclusion: An enhanced emotional intelligence quotient should be considereda primary objective to promote the health of mothers with infant children.