Ependymal cell reactions in spinal cord segments after compression injury in adult rat

Recently, it has been suggested that neural stem cells and neural progenitor cells exist in the ependyma that forms the central canal of the spinal cord. In this study, we produced various degrees of thoracic cord injury in adult rats using an NYU-weight-drop device, assessed the degree of recovery of lower limb motor function based on a locomotor rating scale, and analyzed the kinetics of ependymal cell proliferation and differentiation by proliferating cell nuclear antigen (PCNA), nestin, glial fibrillary acidic protein (GFAP), or GAP-43 immunostaining. The results showed that the time course of the ependymal cell proliferation and differentiation reactions differed according to the severity of injury, and that the responses occurred not only in the neighborhood of the injury but in the entire spinal cord. An increase in the locomotor rating score was related to an increase in the number of PCNA-positive cells, and the differentiation of ependymal cells into reactive astrocytes was involved in injury repair. No apoptotic cells in the ependyma were detectable by the TUNEL method. These results indicate that the ependymal cells of the spinal central canal are themselves multipotent, can divide and proliferate according to the severity of injury, and differentiate into reactive astrocytes within the ependyma without undergoing apoptosis or cell death.     

Uptake of indocyanine green by hepatocytes under inflow occlusion of the liver

BACKGROUND: It is not clear that hepatic venous backflow actually contributes to hepatic tissue oxygenation under inflow occlusion of the liver. In order to prove that substances delivered via the hepatic vein can be utilized and/or metabolized in hepatocytes during inflow occlusion, hepatic uptake in bile and excretion of indocyanine green (ICG) were investigated in pigs. MATERIALS AND METHODS: Animals were divided into two groups: an inflow occlusion (IO) group (N = 6) and a total hepatic vascular exclusion (THVE) group (N = 3) using a bypass. One milligram of ICG per kilogram body weight was administered at the beginning of blood flow occlusion, the retention rate in the blood (ICG R) measured, and the ICG in the hepatic tissue measured by near-infrared (NIR) spectroscopy. Furthermore, the ICG concentration was measured in bile excreted by intermittent perfusion of the liver. RESULTS: ICG R declined with time in both groups; however, ICG R in the IO group decreased much faster than in the THVE group. There were significant differences between the two groups after 30 min of occlusion (P < 0.05). ICG in the hepatic tissue could be detected as a peak at 805 nm 10 min after ICG injection, and the peak became steeper with time. On the other hand, ICG was not detected at all in the hepatic tissue after 180 min in the THVE group. ICG was excreted in the bile after 60 min under IO and increased with time. On the contrary, ICG was not excreted in the bile at all under THVE. There were significant differences between the two groups after 90 min (P < 0.05). CONCLUSION: These results indicate that ICG can be extracted in hepatocytes and excreted in bile under IO of the liver. Consequently, substances such as oxygen and drugs, which are delivered via the hepatic vein, can be utilized and/or metabolized in hepatocytes under IO.     

Primary Sjögren's syndrome initially manifested by optic neuritis: MRI findings

We herein describe the MRI findings in a patient clinically diagnosed with primary Sj?gren's syndrome (SjS) initially manifested by retrobulbar optic neuritis. A 63-year-old woman suddenly had left ocular pain and progressive visual disturbance. MR T2-weighted images revealed hyperintensity in the left optic nerve, with swelling. Contrast-enhanced T1-weighted images showed no abnormal enhancement. Follow-up MRI 6 months after admission revealed no significant changes in the affected optic nerve. To our knowledge, optic neuritis as a complication of SjS has been reported in ten patients [1, 2, 3, 4, 5, 6] and MRI findings in only one of them [6]. We thought MR images were useful for visualizing optic nerve involvement in SjS and observing its course.     

Pilot study of an alternative CYVADIC + CBDCA protocol for adult soft tissue sarcoma as adjuvant chemotherapy

An alternative CYVADIC + CBDCA protocol was tried as a postoperative adjuvant chemotherapy for patients with adult soft tissue sarcoma. The regimen for CYVADIC was day 1: VCR: 1.5 mg/m2 (day 1), doxorubicin: 50 mg/m2 (day 1), DTIC: 250 mg/m2 (day 1-2), and cyclophosphamide: 500 mg/m2 (day 2), and that for CBDCA was 400 mg/m2. CYVADIC and CBDCA were administered alternatively for 3 cycles each. From July 1995 to December 1997, 80 patients with soft tissue sarcoma underwent surgery in our hospital. This protocol was used in 8 of these cases of high grade adult soft tissue sarcoma. Round cell sarcoma was excluded from this study. The 5-year disease free survival rate was 60% and the overall survival rate was 70%. Three cases showed lung metastases. Two patients died of disease and one patient survives free from disease after removal of the lung metastases. No patients showed severe toxicity. We conclude that this protocol merits further evaluation.     

Effects of neonatal hypoxic-ischemic brain injury on skilled motor tasks and brainstem function in adult rats

In an attempt to establish more sensitive long-term neurofunctional measurements for neonatal hypoxic-ischemic brain injury, we examined skilled motor task and brainstem functions in adult rats after neonatal cerebral hypoxia-ischemia (H-I), using a staircase test and auditory brainstem response (ABR), respectively. Seven-day-old rats underwent a combination of left common carotid artery ligation and exposure to 8% O(2) for 1 h (n=16). The control animals only received sham operation (n=16). At 3 months of age, the staircase test and ABR were performed. In the staircase test, H-I animals showed marked impairment of skilled forelimb use in the side contralateral to the occluded artery, and the degree of brain damage correlated significantly to skilled forelimb use. In the ABR, H-I animals showed brainstem dysfunction assessed by measuring interpeak latencies for waves III-V and I-V. We also examined the brainstem with antibodies specific for activated caspase-3, a protein involved in initiation of apoptosis, and observed that caspase-3 was activated in the ipsilateral inferior colliculus at 24 h after H-I. The present study shows that both the staircase test and ABR are sensitive and objective long-term neurofunctional measurements that can be used in future studies to assess therapeutic intervention in this neonatal cerebral H-I model.     

Decision-tree sensitivity analysis for cost-effectiveness of whole-body FDG PET in the management of patients with non-small-cell lung carcinoma in Japan

BACKGROUND: Whole-body 2-fluoro-2-D-[18F]deoxyglucose [FDG] positron emission tomography (WB-PET) may be more cost-effective than chest PET because WB-PET does not require conventional imaging (CI) for extrathoracic staging. METHODS: The cost-effectiveness of WB-PET for the management of Japanese patients with non-small-cell lung carcinoma (NSCLC) was assessed. Decision-tree sensitivity analysis was designed, based on the two competing strategies of WB-PET vs. CI. WB-PET was assumed to have a sensitivity and specificity for detecting metastases, of 90% to 100% and CI of 80% to 90%. The prevalences of M1 disease were 34% and 20%. One thousand patients suspected of having NSCLC were simulated in each strategy. We surveyed the relevant literature for the choice of variables. Expected cost saving (CS) and expected life expectancy (LE) for NSCLC patients were calculated. RESULTS: The WB-PET strategy yielded an expected CS of $951 US to $1,493US per patient and an expected LE of minus 0.0246 years to minus 0.0136 years per patient for the 71.4% NSCLC and 34% M1 disease prevalence at our hospital. PET avoided unnecessary bronchoscopies and thoracotomies for incurable and benign diseases. Overall, the CS for each patient was $833US to $2,010US at NSCLC prevalences ranging from 10% to 90%. The LE of the WB-PET strategy was similar to that of the CI strategy. The CS and LE minimally varied in the two situations of 34% and 20% M1 disease prevalence. CONCLUSIONS: The introduction of a WB-PET strategy in place of CI for managing NSCLC patients is potentially cost-effective in Japan.