Tateki Tsutsui

Detection of interleukin-8 (IL-8) in seminal plasma and elevated IL-8 in seminal plasma of infertile patients with leukospermia.

OBJECTIVE To determine if interleukin-8 (IL-8) is a normal constituent of seminal plasma and if leukospermia is a factor determining its elevation. DESIGN Seminal plasma from 58 men obtained by masturbation was examined for the presence of IL-8 using an IL-8 specific sandwich ELISA. Semen samples were obtained from 34 infertile men without leukospermia, 10 infertile men with leukospermia, and 14 proven fertile men. The correlation of amount of IL-8 in seminal plasma with some spermiogram parameters and the amount of polymorphonuclear (PMN) elastase was statistically evaluated. RESULTS Immunoreactive IL-8 was observed in the seminal plasma of all 58 subjects. The IL-8 titer in seminal plasma of patients with leukospermia (6.16 +/- 0.82 micrograms/L) was significantly higher than that in seminal plasma of patients without leukospermia (2.35 +/- 0.34 micrograms/L) and fertile men (1.64 +/- 0.29 micrograms/L). There was a high degree of correlation between PMN elastase and IL-8 levels in seminal plasma. CONCLUSIONS These findings demonstrate IL-8 to be in seminal plasma and elevated IL-8 levels in infertile patients with leukospermia.

Mouse model of human infertility : Transient and local inhibition of endometrial STAT-3 activation results in implantation failure

Embryo implantation involves a series of biochemical reactions and its failure is an important therapeutic target of infertility treatment. We established an infertile mouse model using transient and local suppression of signal transducer and activator of transcription‐3 (STAT‐3) activity by STAT‐3 decoy transfer into the uterine cavity during implantation, resulting in <30% implantation. This infertility is caused by suppression of decidualization, which is indispensable for implantation, and independent of progesterone. These conditions may mimic clinically unexplained infertility. Our results suggest that STAT‐3 could be a useful target for diagnosis and therapy of human implantation failure.

Uterine cervical carcinoma: preoperative staging with 3.0-T MR imaging--comparison with 1.5-T MR imaging.

PURPOSE To prospectively evaluate the efficacy of 3.0-T magnetic resonance (MR) imaging in the preoperative staging of cervical carcinoma compared with that at 1.5-T imaging, with surgery and pathologic analysis as the reference standards. MATERIALS AND METHODS Institutional review board approval and informed consent were obtained. Thirty-one consecutive patients (age range, 27-71 years; mean age, 51.1 years) underwent 3.0- and 1.5-T MR imaging. Quantitative and qualitative analyses were performed. Two radiologists independently evaluated images in terms of local-regional staging. MR findings were compared with surgicopathologic findings. RESULTS Mean tumor signal-to-noise ratios, mean cervical stroma signal-to-noise ratios, and mean tumor-to-cervical stroma contrast-to-noise ratios at 3.0-T imaging were significantly higher than those at 1.5-T imaging (P = 9.1 x 10(-6), P = 1.8 x 10(-6), and P = .008, respectively). Image homogeneity at 3.0-T imaging was significantly inferior to that at 1.5-T imaging (P = .005). There were no significant differences in terms of the degree of susceptibility artifacts. Interobserver agreement between the two radiologists for local-regional staging was good or excellent (kappa = 0.65-0.89). Sensitivity, specificity, and area under the receiver operating characteristic curve for radiologist 1 in the evaluation of parametrial invasion were (a) 75% for both 3.0- and 1.5-T imaging, (b) 70% for both 3.0- and 1.5-T imaging, and (c) 0.82 for 3.0-T imaging and 0.85 for 1.5-T imaging, respectively. Corresponding values for vaginal invasion were (a) 67% for both 3.0- and 1.5-T imaging, (b) 68% for 3.0-T imaging and 72% for 1.5-T imaging, and (c) 0.62 for 3.0-T imaging and 0.67 for 1.5-T imaging, respectively. Corresponding values for lymph node metastases were (a) 57% for both 3.0- and 1.5-T imaging, (b) 83% for 3.0-T imaging and 88% for 1.5-T imaging, and (c) 0.72 for 3.0-T imaging and 0.78 for 1.5-T imaging, respectively. Neither radiologist noted significant differences between values obtained with 3.0-T imaging and those obtained with 1.5-T imaging (P > .5 for all comparison pairs). CONCLUSION In this study, 3.0-T MR imaging was characterized by high diagnostic accuracy in the presurgical evaluation of patients with cervical carcinoma, although 3.0-T imaging was not significantly superior to 1.5-T imaging.

Reliable predictors of neonatal immune thrombocytopenia in pregnant women with idiopathic thrombocytopenic purpura

Of infants born to women with idiopathic thrombocytopenic purpura (ITP), about 10–15% have transient neonatal immune thrombocytopenic purpura (NITP). Of concern is the lack of a reliable predictor for NITP. We conducted a retrospective study of all pregnancies with ITP at Osaka University Hospital over the past 16 years analyzing a total of 127 pregnancies in 88 women with ITP to assess the predictive value of various clinical factors regarding neonatal platelet count in the current pregnancy. We also reviewed the literature concerning ITP in pregnancy and NITP prediction. Neonatal platelet counts were less than 100 × 109/L in 20 of 130 neonates (15.4%), less than 50 × 109/L in 11 neonates (8.5%), and less than 20 × 109/L in three neonates (2.3%). There was a strong correlation between the first and second sibling regarding the occurrence and the severity of NITP with Spearman correlation coefficient of 0.55 (P = 0.001) at birth and 0.63 (P < 0.0001) at nadir after birth. A maternal platelet count less than 100 × 109/L at delivery showed a statistical trend for an association with the occurrence of NITP (P = 0.043). Moreover, maternal ITP refractory to splenectomy correlated with a higher risk for fetal or neonatal ICH according to the review of the literature. In conclusion, pregnant women who have had a previous offspring with NITP or who have ITP refractory to splenectomy may be at particular risk of delivering an offspring with significant NITP. Management decisions, including mode of delivery, may be altered by the degree of risk for potentially severe NITP. Am. J. Hematol., 2012.

Immunisation with a plasmid DNA vaccine encoding gonadotrophin releasing hormone (GnRH-I) and T-helper epitopes in saline suppresses rodent fertility

Research into active immunisation against gonadotrophin releasing hormone (GnRH-I) has gained widespread acceptance as a means of controlling reproduction and behaviour of farm, companion and wild animals. Many studies describe the use of multiple copies of the self-peptide in linear alignment and conjugation with a large carrier protein to increase the immune response to the peptide. However, problems resulting from carrier protein epitope suppression have seen a diversion of interest into the use of genetic materials to elicit an optimum immune response. In this study, a 533-bp long DNA vaccine was constructed in pcDNAV5-HisB coding for 18.871 kDa GnRH-I-T-helper-V5 epitopes fusion protein. COS1 cells transfected with the vaccine construct were found to release fusion protein into culture supernatant. The vaccine construct (100 microg/mice) in saline solution administered into the anterior quadriceps muscle of ICR male and female mice stimulated antigen-specific IgG antibody responses. Testosterone levels in the vaccinated male mice were significantly (p = 0.021) reduced. A significant reduction in uterine implants were noted following mating between immunised males and control females (p = 0.028), as well as between immunised females and control males (p = 0.004). Histological examination of both the male and female gonads in study week 13 showed atrophy of the seminiferous epithelium and suppression of folliculogenesis.

MR imaging of endometrial carcinoma for preoperative staging at 3.0 T: Comparison with imaging at 1.5 T

To prospectively compare magnetic resonance imaging (MRI) at 3.0 T and 1.5 T in the same patients for preoperative evaluation of endometrial carcinoma.

Acrobeads test: a new diagnostic test for assessment of the fertilizing capacity of human spermatozoa.

OBJECTIVE To determine the effectiveness of the Acrobeads test for predicting the outcome of IVF. DESIGN Human spermatozoa express the CD46 molecule (membrane cofactor protein) on their heads after the acrosome reaction. CD46-positive spermatozoa formed a sperm-bead complex with immunobeads coated with anti-CD46 monoclonal antibody. In the Acrobeads test, fertilizing capacity was determined by assessing sperm-bead agglutination. SETTING Department of Obstetrics and Gynecology, Osaka University Hospital. PARTICIPANTS Thirty-seven donors of proven fertility and 88 male partners of infertile couples. MAIN OUTCOME MEASURES We carried out the Acrobeads test and a sperm penetration assay (SPA) using zona-free hamster oocytes within 3 months before IVF and we then analyzed the results in relation to IVF outcome. RESULTS The sensitivity of the Acrobeads test and SPA was 100% and 88%, respectively, whereas the specificity was 43% and 52%, respectively. The negative predictive value of the Acro-beads test was 100%, whereas that of the SPA was 73%. These results indicate that there was no significant difference between these two tests in terms of predicting IVF outcome. CONCLUSION We suggested that the Acrobeads test be used to evaluate the fertilizing capacity of human spermatozoa because we should avoid using the SPA to prevent cruelty to animals.

Spinal subarachnoid hematoma following spinal anesthesia in a patient with HELLP syndrome

A case of subarachnoid hematoma following spinal anesthesia for cesarean section in a patient with HELLP syndrome is reported. A 39-year-old woman underwent cesarean section under spinal anesthesia for worsening preeclampsia with HELLP syndrome. Despite full recovery from the spinal anesthetic, on the second postoperative day she felt numbness on the posterior aspect of her right leg, noticed she was insensitive to bladder fullness and had mild flaccid paraparesis. Magnetic resonance imaging revealed a spinal subarachnoid hematoma with cauda equina compression. With conservative management she made an almost complete recovery within three months. Serial magnetic resonance imaging showed spontaneous regression of the hematoma. The risk of spinal subarachnoid hematoma following obstetric regional anesthesia is exceedingly small even in a patient with coagulopathy and, to our knowledge, this is only the second reported case following obstetric regional anesthesia. Anesthesia for HELLP syndrome in patients with an adequate platelet count but without disseminated intravascular coagulation is controversial. It is therefore important for clinicians to recognize the symptoms and signs of spinal subarachnoid hematoma to avoid delay in treatment that might result in severe neurological deficit.

The activity of carboplatin and paclitaxel for recurrent cervical cancer after definitive radiotherapy

OBJECTIVES The aim of this study was to evaluate the efficacy of paclitaxel-carboplatin (TC) for recurrent cervical cancer after definitive radiotherapy and to compare the results with non-taxane containing platinum-based chemotherapies (NTP). METHODS The records of 59 consecutive women who had undergone salvage chemotherapy with TC (n=28) or NTP (historical control, n=31) for recurrence after definitive radiotherapy were retrospectively reviewed. Primary disease and recurrence data was collected. The activity and toxicity of TC were compared with those of NTP. The response rate and progression-free survival (PFS) after recurrence were the main endpoints. Multivariate analysis of prognostic factors for response was performed using the Cox proportional hazards regression model. Survival was calculated using the Kaplan-Meier methods and compared by the log-rank test. RESULTS Overall, TC was well tolerated with a response rate of 67.9% (5 CR and 14 PR). The median PFS was 7 months for all patients and 10 months for responders. Myelosuppression was the most common toxicity (grade 3 in 16 patients, grade 4 in 5 patients). On the contrary, NTP showed a response rate of 22.6% with median and mean PFS of 0 month and 2 months, respectively. When compared, TC was significantly superior to NTP with regard to its response rate (p=0.001) and PFS (p<0.0001). Moreover, TC showed significantly higher activity in patients with adenocarcinoma histology. CONCLUSIONS Carboplatin-paclitaxel is active and well tolerated in patients with recurrent cervical cancer after definitive radiotherapy. This combination should be considered as an alternative regimen to cisplatin-paclitaxel in this patient population.

Preparation of oligozoospermic and/or asthenozoospermic semen for intrauterine insemination using the SpermPrep * semen filtration column †

Objective To improve the quality of oligozoospermic and/or asthenozoospermic semen by the SpermPrep (Fertility Technologies Inc., Natick, MA) semen filtration column. Design The SpermPrep column was applied for semen manipulation in oligozoospermia and/or asthenozoospermia (sperm count 6 /mL, sperm motility Setting Department of Obstetrics and Gynecology, Osaka University Hospital. Patients Twenty-one couples with long-standing infertility because of poor quality semen. Main Outcome Measure Recovery of motile sperm, sperm motility, and outcome of IUI were evaluated among three semen preparations. Results Motility was improved by the SpermPrep method in 32 of 33 cases of oligozoospermia and/or asthenozoospermia. Percentage yield of motile sperm by the SpermPrep method was significantly greater than those by the two-layer Percoll density gradient and swim-up methods (42.7±4.6 versus 22.1±3.1 and 13.8±3.5), but there is no significant difference in the sperm motility among three semen preparations. After one treatment cycle for each preparation, 2 of 21 women conceived after IUI with motile sperm separated in the SpermPrep method. Conclusions The SpermPrep method is an improved semen manipulation method for oligozoospermia and/or asthenozoospermia.