Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial.

Recent studies have suggested that long-term oxytocin administration can alleviate the symptoms of autism spectrum disorder (ASD); however, factors influencing its efficacy are still unclear. We conducted a single-center phase 2, pilot, randomized, double-blind, placebo-controlled, parallel-group, clinical trial in young adults with high-functioning ASD, to determine whether oxytocin dosage and genetic background of the oxytocin receptor affects oxytocin efficacy. This trial consisted of double-blind (12 weeks), open-label (12 weeks) and follow-up phases (8 weeks). To examine dose dependency, 60 participants were randomly assigned to high-dose (32 IU per day) or low-dose intranasal oxytocin (16 IU per day), or placebo groups during the double-blind phase. Next, we measured single-nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR). In the intention-to-treat population, no outcomes were improved after oxytocin administration. However, in male participants, Clinical Global Impression-Improvement (CGI-I) scores in the high-dose group, but not the low-dose group, were significantly higher than in the placebo group. Furthermore, we examined whether oxytocin efficacy, reflected in the CGI-I scores, is influenced by estimated daily dosage and OXTR polymorphisms in male participants. We found that >21 IU per day oxytocin was more effective than ⩽21 IU per day, and that a SNP in OXTR (rs6791619) predicted CGI-I scores for ⩽21 IU per day oxytocin treatment. No severe adverse events occurred. These results suggest that efficacy of long-term oxytocin administration in young men with high-functioning ASD depends on the oxytocin dosage and genetic background of the oxytocin receptor, which contributes to the effectiveness of oxytocin treatment of ASD.

Decreased pregnancy rate is linked to abnormal uterine peristalsis caused by intramural fibroids.

BACKGROUND: The relationship between fibroids and infertility remains an unsolved question, and management of intramural fibroids is controversial. During the implantation phase, uterine peristalsis is dramatically reduced, which is thought to facilitate embryo implantation. Our aims were to evaluate (i) the occurrence and frequency of uterine peristalsis in infertile women with intramural fibroids and (ii) whether the presence of uterine peristalsis decreases the pregnancy rate. METHODS: Ninety-five infertile patients with uterine fibroids were examined using magnetic resonance imaging (MRI). Inclusion criteria were as follows: (i) presence of intramural fibroids, excluding submucosal type; (ii) no other significant infertility factors (excluding endometriosis); and (iii) regular menstrual cycles, and MRI performed at the time of implantation (luteal phase day 5-9). The frequency of junctional zone movement was evaluated using cine-mode-display MRI. After MRI, patients underwent infertility treatment for up to 4 months, and the pregnancy rate was evaluated prospectively. RESULTS: Fifty-one patients fulfilled the inclusion criteria, and 29 (57%) and 22 (43%) patients were assigned to the low (0 or 1 time/3 min) or high frequency (≥ 2 times/3 min) uterine peristalsis group, respectively. Endometriosis incidence was the same in both groups. Ten out of the 29 patients (34%) in the low-frequency group achieved pregnancy, compared with none of the 22 patients (0%) in the high-frequency group (P< 0.005). Comparing pregnant and non-pregnant cases, 4 of 10 patients (40%) and 9 of 41 patients (22%), respectively, had endometriosis (not significant). CONCLUSIONS: A higher frequency of uterine peristalsis during the mid-luteal phase might be one of the causes of infertility associated with intramural-type fibroids.

[The current status of assisted reproductive technology].

It has been over two decades since the birth of the first child conceived by in vitro fertilization (IVF). During the intervening years, technology has evolved; however, IVF has not solved the problems concerning sperm. The first successful pregnancies after the intracytoplasmic injection of a single spermatozoon into an oocyte (ICSI) were rapidly followed by the widespread use of this novel technique for the treatment of male factor infertility. Injection of motile (living) spermatozoa into the oocyte is the most important factor in obtaining good results and other sperm parameters, anti-sperm antibodies and sperm origin, i.e., ejaculated, epididymal and testicular, do not have a strong influence on the outcome of ICSI. ICSI has revolutionized the treatment of male infertility and the application of ICSI is rapidly expanding around the world. However, this technique avoids the natural process of sperm selection and fertilization. Therefore, it is of utmost importance to monitor carefully the development, throughout childhood and into adulthood, of individuals born as a result of ICSI in order to assess its safety. ICSI should only be used for specific indications until its safety has been established. In this paper, the current status of two new approaches, ICSI with spermatid and donor oocyte cytoplasm transfusion, is also reviewed.

Reference values of plasma lipoprotein (a) in newly classified apolipoprotein(a) phenotype groups in the Japanese population.

We tried to establish the reference values of plasma lipoprotein (a) [Lp(a)] concentration in phenotype groups of apoliprotein(a) [apo A] classified by a new criterion. Lp(a) concentration was determined by latex agglutination immunoassay, and apo A was analysed by electrophoresis in sodium dodecyl sulphate-polyacrylamide gel and a Western blotting technique. According to the relative mobility to the apo B-100 band, apo A was classified into 11 isoforms, i.e. F, B, and S1-S9, and the phenotype was defined by their apparent combination. The frequency ratio of single-band versus double-band was approximately 2:1. In 382 cases of single-band, the most frequent phenotype was S5 (24.3%), followed by S4 (17.3%), S6 (15.4%) and S3 (14.4%). In 181 cases of double-band, S5/S6 phenotype was observed most frequently (12.2%). followed by S4/S5 (10.5%) and S3/S6 (7.2%). The reference value was determined between antilogs of the mean +/- 1.96 standard deviation by logarithmic transformation of all observed values for individual phenotype cases. These results suggest that the reference values shown to be variable with apo A phenotypes should be useful for evaluating Lp(a) values in diagnosis of atherosclerosis.

[Beta(+)-thalassemia (-31CapA-->G) homozygosity discovered on the mass medical examination: diagnosis for beta-thalassemia and DNA analysis].

A 44-year-old Japanese male showed a high value of HbF (14.3%) in an assay of glycated Hb (HbA1c) by use of HLC-723GHb II system. The proband was asymptomatic although he was found to be anemic ten years ago. The hematological examination revealed microcytosis, hypochromia and slight reticulocytosis (3.7%). Serum iron level was high (245 g/dl). Blood smear revealed aniso-poikilocytosis with scattered target cells. Hb analysis showed a remarkable increase of HbA2 (8.6%) as well as the high HbF cited above, but no abnormal Hb was detected. The beta/alpha ratio of globin biosynthesis in reticulocytes was decreased to 0.25. DNA sequencing of the beta-globin gene disclosed that the proband was homozygous for beta (+)-thalassemia mutation-31CapA-->G. This mutation was linked to A gamma T gene and haplotype -(-)+2(-)+2-. His parents and two daughters were heterozygous for the mutation. They were anemic and had increased HbA2 levels of 4.36-5.43%. The beta/alpha ratios of globin biosynthesis were 0.61-0.81.

[Hb M-Iwate [alpha 87 (F8) His-->Tyr]: analysis of the genomic DNA and biosynthesis].

Hb M-Iwate [alpha 87 (F8) His-->Tyr] was identified as the cause of cyanosis in a 21-year-old Japanese female. Amplification and sequencing of the alpha 2- and alpha 1-genes demonstrated the mutation CD87 CAC (His)-->TAC (Tyr) in the alpha 2-gene. Analysis of the in vitro globin biosynthesis in the reticulocytes disclosed a well-balanced beta/alpha synthetic ratio of 1.04 but an unexpectedly low alpha M/total alpha. Although the cause of the lowered alpha M-globin biosynthesis is not yet clear, it might be related to a defect in chain assembly rather than to a modified stability or a reduced amount of the abnormal alpha-globin mRNA.