Proliferative lesions of oviduct and uterus in CD-1 mice exposed prenatally to tamoxifen

Tamoxifen (TAM) is widely used as adjuvant breast cancer therapy after surgery and as a chemopreventive agent in women of child-bearing age. However, TAM therapy has been shown to result in an increased incidence of endometrial carcinoma in women. The present study was designed to investigate the effects of TAM (5 mg/kg and 7.5 mg/kg body wt) given i.g. to pregnant CD-1 mice (1x/day, days 12 through 18 of gestation) on their female offspring. Progressive proliferative hyperplasia of the oviduct was frequently seen in TAM-exposed offspring, reaching 100% incidence by 52 weeks in both treatment groups. These females also developed progressive proliferative uterine lesions, including moderate/severe cystic endometrial hyperplasia (34-50%) and polypoid adenomas (27-30%) between 53 and 78 weeks. Deciduomas (15%) occurred at young ages (12 and 24 weeks) while leiomyomas (14%), a malignant leiomyosarcoma, and ovarian granulosa cell tumors (14%), were found between 72 and 78 weeks. Our findings thus suggest a strong association between transplacental TAM and reproductive tract abnormalities in female CD-1 mice.      

The efficacy of the ketogenic diet-1998: a prospective evaluation of intervention in 150 children

OBJECTIVE: The ketogenic diet is a high-fat, low-protein, low-carbohydrate diet developed in the 1920s for the treatment of children with difficult to control seizures. Despite advances in both the pharmacotherapy and the surgery of epilepsy, many children continue to have difficult-to-control seizures. This prospective study sought to determine the ketogenic diet's effectiveness and tolerability in children refractory to today's medications. METHODS: One hundred fifty consecutive children, ages 1 to 16 years, virtually all of whom continued to have more than two seizures per week despite adequate therapy with at least two anticonvulsant medications, were prospectively enrolled in this study, treated with the ketogenic diet, and followed for a minimum of 1 year. Seizure frequency was tabulated from patients' daily seizure calendars and seizure reduction calculated as percentage of baseline frequency. Adverse events and reasons for diet discontinuation were recorded. RESULTS: The children (mean age, 5.3 years), averaged 410 seizures per month before the diet, despite an exposure to a mean of 6.2 antiepileptic medications. Three months after diet initiation, 83% of those starting remained on the diet and 34% had >90% decrease in seizures. At 6 months, 71% still remained on the diet and 32% had a >90% decrease in seizures. At 1 year, 55% remained on the diet and 27% had a >90% decrease in seizure frequency. Most of those discontinuing the diet did so because it was either insufficiently effective or too restrictive. Seven percent stopped because of intercurrent illness. CONCLUSIONS: The ketogenic diet should be considered as alternative therapy for children with difficult-to-control seizures. It is more effective than many of the new anticonvulsant medications and is well tolerated by children and families when it is effective.     

Mononucleosis syndrome and coincidental human herpesvirus-7 and Epstein-Barr virus infection

Two girls (a 5 year old and a 21 month old) experiencing mononucleosis syndrome with coincidental human herpesvirus (HHV)-7 and Epstein-Barr virus (EBV) infections are described. One patient had primary HHV-7 infection and reactivated EBV infection. The other had primary HHV-7 and EBV infections. These cases indicated that HHV-7 is capable of inducing infectious mononucleosis-like illness. Multiple herpesvirus infection in one of the patients also suggests that interaction among herpesviruses can occur in vivo. The consequence of this interaction may have clinical implications.     

Sex differences in response to red and blue light in human primary visual cortex: a bold fMRI study

Studies using a variety of investigative methods, including functional brain imaging and electroencephalography (EEG), have suggested that changes in central nervous system (CNS) dopamine function result in altered visual system processing. The discovery of abnormal retinal blue cone, but not red cone, electroretinogram in association with cocaine withdrawal and Parkinson's disease suggests that visual system response to blue light might be a marker for CNS dopamine tone. As there are numerous sex-related differences in central nervous system dopamine function, we predicted that blue and red light stimulation would produce sex-specific patterns of response in primary visual cortex when studied using the blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) technique. We analyzed the BOLD response to red and blue light in male and female human volunteers (N=20). Red and blue light responses in primary visual cortex (V1) to stepped intensities of red and blue light were compared by sex for threshold to detectable BOLD signal increase and for stimulus intensity vs. BOLD signal response. Near threshold, males and females showed similar BOLD signal change to red light, but males showed a threefold greater increase (0.52%) to blue light stimulation when compared to females (0.14%). Log-linear regression modeling revealed that the slope coefficients for the red light stimulus intensity vs. signal change curve were not significantly different for males and females (z=0.995, P=0.320), whereas the slope coefficients for the blue light stimulus intensity vs. signal change curve were significantly larger in males (z=2.251, P=0.024). These findings support a sex and color-dependent differential pattern of primary visual cortical response to photic stimulation and suggest a method for assessing the influence of specific dopamine agonist/antagonist medications on visual function.     

纳洛酮治疗原发性脑干损伤

目的 :观察纳洛酮治疗原发性脑干损伤的疗效。方法 :83例原发性脑干损伤病人分为纳洛酮组 38例 ,在常规治疗基础上加用纳洛酮 0 .3mg·kg- 1加入氯化钠注射液 5 0 0mL中静脉滴注 ,qd× 3d ,3d后减为 4 .8mg·d- 1,qd× 7d ,10d为一个疗程 ;常规治疗组 4 5例 ,单用常规治疗。按格拉斯哥昏迷评分标准观察病人症状。结果 :常规治疗组和纳洛酮组的昏迷时间分别为 (30±s 4 )d和 (2 0±4 )d ,死亡分别为 16例和 6例 ,恢复良好分别为 12例和 2 3例 ,中残分别为 7例和 6例 ,重残分别为 10例和 3例、植物生存各 1例 ;2组昏迷时间及疗效比较 ,P <0 .0 1。结论 :纳洛酮在原发性脑干损伤的治疗中能降低死亡率 ,缩短昏迷时间 ,减少残存率。     

Effects of Fluvastatin on the Pharmacokinetics of Repaglinide: Possible Role of CYP3A4 and P-glycoprotein Inhibition by Fluvastatin

The purpose of this study was to investigate the effects of fluvastatin on the pharmacokinetics of repaglinide in rats. The effect of fluvastatin on P-glycoprotein and CYP3A4 activity was evaluated. The pharmacokinetic parameters and blood glucose concentrations were also determined after oral and intravenous administration of repaglinide to rats in the presence and absence of fluvastatin. Fluvastatin inhibited CYP3A4 activity in a concentration-dependent manner with a 50% inhibition concentration(IC₅₀) of 4.1 µM and P-gp activity. Compared to the oral control group, fluvastatin significantly increased the AUC and the peak plasma level of repaglinide by 45.9% and 22.7%, respectively. Fluvastatin significantly decreased the total body clearance (TBC) of repaglinide compared to the control. Fluvastatin also significantly increased the absolute bioavailability (BA) of repaglinide by 46.1% compared to the control group. Moreover, the relative BA of repaglinide was 1.14- to 1.46-fold greater than that of the control. Compared to the i.v. control, fluvastatin significantly increased the AUC_0-∞ of i.v. administered repaglinide. The blood glucose concentrations showed significant differences compared to the oral controls. Fluvastatin enhanced the oral BA of repaglinide, which may be mainly attributable to the inhibition of the CYP3A4-mediated metabolism of repaglinide in the small intestine and/or liver, to the inhibition of the P-gp efflux transporter in the small intestine and/or to the reduction of TBC of repaglinide by fluvastatin. The study has raised the awareness of potential interactions during concomitant use of repaglinide with fluvastatin. Therefore, the concurrent use of repaglinide and fluvastatin may require close monitoring for potential drug interactions.     

Image Fusion of Real-Time Ultrasonography with Computed Tomography: Factors Affecting the Registration Error and Motion of Focal Hepatic Lesions

Factors affecting the registration error (RE) and motion of focal hepatic lesions (FHLs) in image fusion of real-time ultrasonography (US) with computed tomography (CT) images were prospectively assessed by focusing on respiratory movement and FHL location. Real-time US and pre-acquired CT images at end-inspiration were fused with FHLs for 103 patients. Three-dimensional US data containing FHLs were obtained during end-inspiratory/expiratory phases. Multivariate analysis revealed that diaphragm motion (p < 0.001), chronic liver disease (p = 0.02) and the absolute difference in distance between the FHL and the central portal vein (CPV) during respiration (p = 0.03) were the independent factors that revealed the maximum effect on RE. In contrast, diaphragm motion (p < 0.001) and distance between the FHL and CPV at inspiration (p = 0.036) revealed the maximum effect on FHL motion. In conclusion, RE and FHL motion are affected by the degree of respiratory movement and the location of the FHL. Therefore, image fusion with CT images should be used with caution if the degree of respiratory motion is significant or if the FHL is located at the periphery of the liver.