Oral-motor patterns of rhythmic trigeminal activity generated in fetal rat brainstem in vitro

Development of neural circuits generating fetal oral-motor activity was characterized in an in vitro isolated brainstem block preparation. Rhythmical trigeminal activity (RTA) at E20-E21 resembled either the pattern or rhythm of neonatal RTA. Conversely, at E18-E19, RTA displayed a different pattern of discharge from neonatal RTA, and output was not regular but intermittent with another slow rhythm.     

Evaluation of ultra-low-dose thoracic multi-detector-row CT using different reconstruction kernels and new reconstruction algorithms

CT has great advantages in detecting early-stage small lung cancer and is becoming common in lung cancer screening. Multi-detector-row CT (MDCT) can provide thin-slice images with low radiation exposure. In this study, ultra-low-dose (5 mAs: 10 mAs, 0.5 sec/rot) thoracic MDCT images were evaluated. We describe the differences in image quality and quantity between the different reconstruction kernels. We also propose a new reconstruction algorithm (ultra-low-dose reconstruction algorithm: ULR) for ultra-low-dose thoracic CT, to reduce noise and streak artifacts. We are convinced of the usefulness and possibility of ultra-low-dose thoracic MDCT with ULR algorithms for lung cancer screening.     

Diagnosis and treatment of extramammary Paget's disease

Extramammary Paget's disease is a malignant tumor with the characteristic bright large atypical cells called Paget's cells, which proliferate within an intraepidermal lesion outside the breast. It occurs most frequently in the external genitalia, followed by perianal and axillary regions. The main clinical symptoms are erythema, erosion, pigmentation and depigmentation. Extramammary Paget's disease is commonly an intraepidermal neoplasm. However, if the tumor cells infiltrate into the dermis and form a clinically manifest nodule, it becomes an invasive carcinoma that can be classified as adnexal adenocarcinoma of the skin. Surgery with wide local excision is the first choice of treatment, and the prognosis is comparatively favorable in the early stages. However, when tumor cells infiltrate into the dermis and advance to Paget's carcinoma, it is referred to as adenocarcinoma of the skin and has a poor prognosis. We report an effective treatment of extramammary Paget's disease in advanced stages' including our case. No standard treatment with a significant effect has yet been established. There are few reports of cases responsive to chemotherapy, and treatment in advanced stages is extremely difficult at present.     

Reduction of the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice using an antiulcer drug, geranylgeranylacetone

The protective effect of geranylgeranylacetone (GGA), an antiulcer drug, against the acute toxicity and teratogenicity produced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was examined in C57BL/6J mice. When mice were co-treated, GGA reduced the loss of body weight gain and lethality produced by TCDD but hepatomegaly and thymic atrophy were not improved. Additionally, no protective effect of GGA was observed in the formation of cleft palate and hydronephrosis in mouse fetuses caused by maternal exposure to TCDD. To clarify the reducing mechanism by GGA, the Hsp70.1 mRNA levels in liver and intestine were analyzed. However, it was difficult to explain the effect of GGA from the induction of Hsp70.1. GGA had also no effect on the induction of hepatic ethoxyresorufin O-deethylase activity by TCDD. These data suggest that GGA exhibits a protective effect against some forms of dioxin toxicity by a mechanism without involving inhibition of arylhydrocarbon receptor activation.     

Observation of time-dependent adverse events and the influence of drop-out thereon in long-term safety studies--simulation study under the current practice of post-marketing safety evaluation in Japan

Safety assessment of a new drug should be continuously carried out in the premarketing phase as well as in the postmarketing phase. Considering the actual conditions and problems of postmarketing safety studies in Japan, i.e., the lack of attention to the extent of patients' exposure to the drug (duration and the number of patients), we simulated the number of adverse events to be observed after specified intervals of exposure. This was done by applying different sets of hazard functions for a Weibull distribution under the circumstances that a certain number of patients has dropped out, focusing on rare and delayed adverse events associated with chronically used drugs. By using the result of these simulations, we point out potential problems of underestimating adverse event rates in situations where the hazard rate of the event escalates over time. Patients drop-out from the study also deteriorates the ability to observe such time-dependent adverse events. The simulation can also serve as a useful tool to examine the necessary sample size and the duration of exposure in order to observe and characterize potentially expected adverse events. It is important to take the two key factors into consideration: the change of hazard function over time and the effect of drop-out in designing, analyzing, and evaluating safety studies for new drugs.     

Effect of etidronate on three-dimensional trabecular structure in ovariectomized or sciatic neurectomized rats

The purpose of this study was to evaluate the effect of etidronate (EHDP) on three-dimensional (3D) trabecular structure in ovariectomized (OVX) and sciatic neurectomized (NX) rats. Eight-week-old female Lewis rats received ovariectomy (n = 19) or sham operation (OVX-sham; n = 10). OVX rats received either vehicle (OVX-control; n = 9) or EHDP (OVX-EHDP; n = 10). Eight-week-old female Lewis rats received NX (n = 20) or sham operation (NX-sham; n = 10). NX rats received either vehicle (NX-control; n = 10) or EHDP (NX-EHDP; n = 10). EHDP at 5mg/kg or vehicle was subcutaneously injected 5 days a week. The treatment was initiated 2 weeks after surgery and was continued for 2 weeks. At 12 weeks of age, the rats were killed, and we scanned the proximal metaphysis of the tibia; this was done using micro-CT; ( CT20; SCANCO Medical). The recovery of structural parameters was not complete in NX rats compared to OVX rats. The 3D micro-CT images showed that the subcortical spongiosa, which was preserved in OVX rats, had marked loss in NX rats. Furthermore, these trabeculae were not restored after the EHDP treatment. In conclusion, the mechanical driving of the control of trabecular structure is inactive in NX, and EHDP treatment for 2 weeks does not restore this condition.     

Periosteal chondroma of the fifth toe--a case report

A case of a periosteal chondroma arising in the fifth toe is reported. A 19-year-old man presented a palpable mass of his left fifth toe with pain for 2 years. Plain radiographs showed mild irregularity of the cortical bone of the fifth proximal phalanx. Magnetic resonance imaging revealed a tumour attached to the fifth proximal phalanx with low signal intensity on T1-weighted images and high signal intensity on T2-weighted images without intramedullary extension. The tumour was enhanced heterogeneously after intravenous injection of gadolinium diethylene triamine penta-acetic (GD-DTPA). The tumour was removed, together with the covering periosteum. It was diagnosed as periosteal chondroma histologically.     

A Use of Monte Carlo Integration for Population Pharmacokinetics with Multivariate Population Distribution

This paper describes a use of Monte Carlo integration for population pharmacokinetics with multivariate population distribution. In the proposed approach, a multivariate lognormal distribution is assumed for a population distribution of pharmacokinetic (PK) parameters. The maximum likelihood method is employed to estimate the population means, variances, and correlation coefficients of the multivariate lognormal distribution. Instead of a first-order Taylor series approximation to a nonlinear PK model, the proposed approach employs a Monte Carlo integration for the multiple integral in maximizing the log likelihood function. Observations below the lower limit of detection, which are usually included in Phase 1 PK data, are also incorporated into the analysis. Applications are given to a simulated data set and an actual Phase 1 trial to show how the proposed approach works in practice.     

Hepatocellular carcinoma with obstructive jaundice successfully treated with a self-expandable metallic stent

We report on a 71-year old man with hepatocellular carcinoma (HCC) whose obstructive jaundice was successfully treated with external irradiation and a self-expandable metallic stent (EMS); Wallstent; Schneider (Europe) AG, Bülach, Switzerland. He was admitted to our hospital because of jaundice. HCC was found in S8; the tumor had invaded the bile duct with growth in the common hepatic duct. Endoscopic nasobiliary drainage was performed with difficulty. Radiation therapy to the stenosis enabled us to place a Wallstent endoscopically. He survived without icterus for 1 year. (Received Oct. 31, 1997; accepted May 22, 1998)