Reproductive Effects of Early Neonatal Exposure to Diethylstilbestrol or Tamoxifen in Rats

To evaluate the effects of potential estrogenic or anti-estrogenic compounds on reproduction, male and female Sprague-Dawley rats were injected subcutaneously with 50 μg/kg diethylstilbestrol (DES) or 20 mg/kg tamoxifen (TAM) from postnatal day 1 to 5. Growth, estrous cycle, locomotor activity, and reproductive function including masculine sexual behavior, sperm motion, and development of reproductive organs were examined. Decrease in body weight gain and abnormal estrous cycle, such as persistent estrous, or prolonged estrous cycle were observed following early neonatal exposure to DES or TAM, while there was no effect on locomotor activity evaluated in the open field in the DES-or TAM-treated group. A marked decrease in sperm motility was found in the TAM-treated group. Anatomical and histological alterations of reproductive organs were observed in male and female rats in the DES-treated group and in female rats in the TAM-treated group. Early neonatal exposure to DES or TAM affected the masculine sexual behavior, resulting in a marked decrease in the ability to copulate and in fertility. In matings of the DES-or TAM-treated rats and intact rats, none of the treated females copulated successfully, whereas approximately 30% of treated males showed normal fertility. These results suggested that early neonatal exposure to DES or TAM induced more marked reproductive dysfunction after puberty in females than in males.     

Real-world Experience of Carotid Artery Stenting in Japan: Analysis of 7,134 Cases from JR-NET1 and 2 Nationwide Retrospective Multi-center Registries

The present study aimed to demonstrate the “real-world” experiences of carotid artery stenting (CAS) in Japan using Japanese Registry of Neuroendovascular Therapy (JR-NET) 1 and 2, retrospective nationwide multi-center surveillances. JR-NET1 and 2 registries are retrospective surveillances conducted between January 2005 and December 2007 and January 2008 and December 2009, respectively, in Japan regarding neuroendovascular therapy. A total of 7,134 procedures (1,943 for JR-NET1 and 5,191 for JR-NET2) were included in this study and retrieved data were analyzed retrospectively. Treatment results of two surveillance periods were similar. In JR-NET2 registry, total of 5,191 lesions were treated by CAS and 5,008 of 5,191 procedures (96.5%) were performed by the board-certified surgeons of Japanese Society of Neuroendovascular Therapy. The rate of technical success was extremely high (99.99%), and the rate of clinically significant complication was low (3.2%). These results were comparable to a previous large study in Japan. Multivariate logistic analysis revealed that age [odds ratio (OR), 1.04 per year; 95% confidence interval (CI), 1.02–1.07; p = 0.0004), symptomatic lesion (OR, 1.87; 95% CI; p = 0.0004), and the use of closed-cell type stent (OR, 0.58; 95% CT, 0.32–1.00; p = 0.05) were independently associated with clinically significant complications. It was revealed that good clinical results were achieved in patients who underwent CAS in Japan. It is expected that the evolution of devices and increasing experiences of surgeons would lead to further improvement of the clinical results, and further investigation would be required to clarify the optimal treatment strategy and therapeutic efficacy of CAS, especially in symptomatic lesions.     

Evaluation of Antibiotic-loaded Calcium Phosphate Bone Cement in a Cranium-infected Experimental Model

Treatment of calvarial defects has remained a challenge in reconstruction surgery, especially because of infection at these sites. We produced a bactericidal biomaterial for treating infected bone defects by using calcium phosphate bone cement mixed with antibiotics. We evaluated the usefulness of this material mixed with the antibiotic vancomycin in a cranium-infected rat model. The concentration of vancomycin used was 5.0 wt%, as reported in our previous study. In order to establish the rat model, a cranium defect (diameter, 5 mm) was made that was infected with methicillin-resistant Staphylococcus aureus (MRSA). Thirty-six rats were divided into 6 groups depending on whether an autologous graft or bone cement with or without antibiotic was used for the defect. After 1 and 4 weeks, abscess formation was checked, tissue bacterial counts were determined, and pathological examination was performed. At both 1 and 4 weeks, no MRSA was detected on tissue bacterial culture or pathological examination in groups that received bone cement with antibiotics. In groups that received bone cement without antibiotic, MRSA was detected, and the bone cement had compromised and disintegrated into several slices. In conclusion, bone cement that contains antibiotics appears to be effective not only for reconstruction in cases of cranial defect, but also in terms of preventing infection.     

Leiomyoma of the urinary bladder during pregnancy

We present a rare case of leiomyoma of the urinary bladder that was diagnosed during pregnancy. To our knowledge, this is the fourth case of its kind to be reported in the literature. Ultrasonography, magnetic resonance imaging and biopsy were useful for making an accurate diagnosis in this case. The diagnosis was confirmed by suprapubic transcutaneous needle biopsy. The tumor was resected approximately 3 years after diagnosis, during which period the patient delivered a normal baby by caesarian section.     

Acute Changes in Left Atrial and Left Ventricular Diameters After Physiological Pacing

The present study examined alterations in left atria! diameter (LAD) and diastolic left ventricular diameter (LVDd) in 37 patients (72.2 ± 9.8 years old) who received physiological pacemakers; 22 with atrioventricular (AV) block and 15 with sick sinus syndrome (SSS). After pacemaker implantation, LAD and LVDd were serially measured using echocardiography, and their diameters ware expressed per body surface area (LADI and LVDdl; mm/m). Pulmonary capillary wedge pressure (PCWP) and cardiac output (CO) were measured in ten patients with SSS and ten with AV block during both right ventricular and AV sequential pacing. After AV sequential pacing, CO increased in 19 of 20 patients (3.2 ± 0.9 L/min to 3.9 ± 1.0 L/min: P < 0.001). LADI decreased from 24.9 ± 4.2 mm/m² to 21.8 ± 4.4 mm/m² (P < 0.001) in 22 patients with AV block and from 24.1 ± 3.4 mm/m² to 20.4 ± 3.8 mm/m² (P < 0.001) in 15 SSS patients. However, LVDdl did not change significantly in either group of patients. The changes in LAD after the implantation of a physiological pacemaker occurred rapidly, i.e. LAD began to decrease within 1 minute after the procedure, and then reached a plateau. This plateau phase continued for at least 7 days during physiological pacing. There was a positive correlation between the changes in LADI after pacemaker implantation and those in PCWP observed during the AV sequential pacing performed prim- to the implantation (r = 0.86; P < 0.001). The reduction in LAD following pacemaker implantation was rapid and seemed to be accompanied by improvement of cardiac function. Thus, it is suggested that the serial measurement of LADI is useful to predict the efficacy of physiological pacemaker implantation.     

Reduced amount of intestinal mucus by treatment with anti-CD4 antibody interferes with the spontaneous cure of Nippostrongylus brasiliensis-infection in mice

Mechanism of spontaneous cure was studied in mice infected with mouse-nonadaptive Nippostrongylus brasiliensis. Adult BALB/c mice were cured spontaneously of infection with this strain of N. brasiliensis by Day 7 post-infection. Expulsion of intestinal worms was delayed dose-dependently by a treatment with anti-CD4 antibody. However, the treatment had no significant effect on larval recovery from the lungs. Treatment of mice with anti-IL-5 antibody suppressed intestinal tissue eosinophilia induced by the infection, but did not affect intestinal worm recovery. Antigen specific IgE antibody was not detected in the sera obtained from Days 5 to 15. Therefore, IL-5 and specific IgE antibody are probably not important in the spontaneous cure. Treatment of mice with anti-CD4 antibody had no significant effect on number of intestinal goblet cells or on expression of terminal sugars of goblet cell mucins. However, histological and quantitative analyses revealed that significantly less intestinal mucus was released in anti-CD4 antibody treated mice than in control mice. These results suggest that CD4+ lymphocytes control the amount of intestinal mucus and consequently the reduced mucus interferes with the spontaneous cure. Quantity of mucus released in the intestinal lumen may have an essential role in the spontaneous cure ofN. brasiliensis-in/fcfio/i of mice.     

Colony-Stimulating Factor Producing Carcinoma of the Gallbladder

A patient with an anaplastic carcinoma of the gallbladder accompaniedby marked neutrophilia was found to have high colony-stimulatingfactor (CSF) activity in the urine and serum. The supernatantof the cultured tumor cells (6th passage) showed high and specificCSF activity. These specimens induced the formation of granulocytecolonies, macrophage colonies or granulocyte macrophage mixedcolonies by both human and C57BL mouse bone marrow cells insoft agar. These results suggest that this tumor is a human granulocyte-macrophage(GM)-CSF producing tumor.     

TREATMENT OF POLYCYSTIC OVARIAN DISEASE BY INDUCING OVULATION WITH PULSATILE SUBCUTANEOUS ADMINISTRATION OF HUMAN MENOPAUSAL GONADOTROPHIN ASSOCIATED WITH LUTEINIZING HORMONE-RELEASING HORMONE ANALOGUE

Treatment with a combination of luteinizing hormone-releasing analogue (GnRHa, Buserelin) and pulsatile administration of hMG (Group I) were used to induce ovulation in nine patients with polycystic ovary syndrome (PCO). The same patients were also treated with pulsatile hMG administration alone (Group II). Ovulation was observed in all twelve treatment cycles in Group I, and there were two pregnancies. In Group II, ovulation occurred in 22 of 26 treatment cycles. Ovarian hyperstimulation occurred in one cycle of Group I and in 5 of 26 cycles of Group II. The total dose per cycle of hMG to induce ovulation in Group I was significantly lower than that needed when only pulsatile hMG administration was used. In response to Buserelin administration, the concentrations of serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) increased transiently and then declined to the normal range observed in the early follicular phase. The concentrations of FSH increased in response to hMG administration, resulting in a normal LH/FSH ratio. The present data demonstrated that pulsatile subcutaneous administration of hMG in addition to Buserelin was effective in inducing follicular maturation and ovulation in patients with PCO with a lower incidence of serious side-effects.