Intraarterial concomitant chemoradiation for tongue cancer: analysis of 20 patients

Subjects were 20 patients with tongue cancer treated between April 1996 and December 2002 with intraarterial infusion of cisplatin (60-120 mg/m2) (and docetaxel 10-30 mg/m2) and intravenous infusion of sodium thiosulfate followed by 5-fluorouracil (5-FU) (800-1000 mg/m2) for 3 to 5 days. All patients underwent radiation (50-80 Gy). Ten had stage II, 4 stage III, and 6 stage IV A disease. Complete response at the primary site was achieved in 50% for T2, 67% for T3, and 0% for T4 lesions in those undergoing IA cisplatin followed by systemic 5-FU with concurrent radiation. Complete response at the primary site was achieved in all patients given IA cisplatin and docetaxel followed by systemic 5-FU with concurrent radiation. Disease-specific survival was 75% and overall survival 69% at 5 years. Side effects of treatment were tolerable, except for grade three radiomucositis in 70% of patients and grade three bone marrow depression in one treated with weekly IA chemotherapy.     

Implanted cannula-mediated repetitive administration of Abeta25-35 into the mouse cerebral ventricle effectively impairs spatial working memory

Amyloid beta (Abeta) is closely related to the onset of Alzheimer's disease (AD). To construct AD animal models, a bolus administration of a large dose of toxic Abeta into the cerebral ventricles of rodents has been performed in earlier studies. In parallel, a continuous infusion system via an osmotic pump into the cerebral ventricle has been developed to make a rat AD model. In this study, we developed a mouse AD model by repetitive administration of Abeta25-35 via a cannula implanted into the cerebral ventricle. Using this administration system, we reproducibly constructed a mouse with impaired spatial working memory. In accordance with the occurrence of the abnormal mouse behavior, we found that the number of choline acetyltransferase (ChAT)-positive neurons was reduced in paraventricular regions of brains of Abeta25-35-administered mice in a dose-dependent manner. Considering that the repetitive administration of a small dose of toxic Abeta via an implanted cannula leads to a brain status more resembling that of the AD patients than a bolus injection of a large dose of Abeta, and therapeutic as well as toxic agents are able to be repeatedly and reliably administered via an implanted cannula, we concluded that the implanted cannula-bearing AD mouse model is useful for development of new AD therapy.     

Histological changes in the rabbit kidney induced by transarterial injection of a hypertonic sodium chloride solution

PURPOSE: To evaluate histological changes in normal renal tissue induced by the injection of a hypertonic liquid. MATERIALS AND METHODS: Transarterial injection was performed in 17 healthy rabbits at various rates of infusion and amounts of isotonic and hypertonic (7%) sodium chloride solutions. In group 1, 10 cc of isotonic sodium chloride solution was injected. In groups 2 and 3, 1-10 cc of hypertonic solution was injected at rates of 1.0 cc/sec and 0.05 cc/sec, respectively. After 20 minutes of hemostasis, renal weight measurements and histological examinations were performed. In three rabbits that received 10 cc of 7% sodium chloride, lung samples were also obtained, and histological changes were reviewed. RESULTS: There was no tissue injury in group 1, and in groups 2 and 3 the histological changes for infusions of 4-10 cc were greater than those of 1-3 cc. There was no vascular endothelial cell damage in any case. None of the histological changes were dose dependent, and the lungs showed no clear histological alterations. CONCLUSION: Higher doses of a hypertonic sodium chloride solution cause irreversible histological changes in the rabbit kidney.     

Imaging of intraneural edema by using gadolinium-enhanced MR imaging: experimental compression injury

BACKGROUND AND PURPOSE: Compressive and entrapment neuropathies are diseases frequently observed on routine clinical examination. A definitive diagnosis based on clinical symptoms and neurologic findings alone is difficult in many cases, however, and electrophysiologic measurement is used as a supplementary diagnostic method. In this study, we examined to use protein tracers (Evans blue albumin or horseradish peroxidase) and gadolinium-enhanced MR imaging to determine the changes of blood-nerve barrier permeability in compressive neuropathies. METHODS: In dogs, the median nerve was compressed for 1 hour by using five kinds of clips with various strengths (7.5-90-g force). After clip removal, the combined tracers of Evans blue albumin and gadolinium or horseradish peroxidase was administered intravenously as a tracer. After the animals were euthenized, we compared gadolinium-enhanced MR images with Evans blue albumin distribution in the nerve under fluorescence microscopy. The horseradish peroxidase-injected specimens were observed by transmission electron microscopy. RESULTS: On enhanced MR imaging, intraneural enhancement was caused by 60- and 90-g-force compression after 1 hour. Marked extravasation of protein tracers in the nerve occurred where there was compression by 60- and 90-g-force compression, and capillaries in the nerve showed the opening of tight junction and an increase of vesicular transport under the electron microscopy. This situation indicated breakdown of the blood-nerve barrier, with consequent edema formation and was seen as enhancement on MR imaging. CONCLUSION: Gadolinium-enhanced MR imaging can detect morphologic and functional changes of blood-nerve barrier in the nerve induced by mechanical compression.     

Hydrogen absorption behavior of beta titanium alloy in acid fluoride solutions

Hydrogen absorption behavior of a beta titanium alloy in acid fluoride solutions has been analyzed by hydrogen thermal desorption. The amount of absorbed hydrogen increased with immersion time in a 2.0% acidulated phosphate fluoride (APF) solution. In the case of an immersion time of 60 h, the amount of absorbed hydrogen exceeded 10000 mass ppm. In contrast, the amount of hydrogen absorbed in the 0.2% APF solution was several times smaller than that in the 2.0% APF solution for the same immersion time. For immersion in a 0.2% APF solution, hydrogen absorption saturated after 48 h. The surface topography and corrosion products on the surface of the specimen immersed in the 2.0% APF solution were different from those in the 0.2% APF solution. During the later stage of immersion, the amount of absorbed hydrogen markedly increased under higher applied stress, although the applied stress did not enhance hydrogen absorption during the early stage of immersion. These results of hydrogen absorption behavior are consistent with the delayed fracture characteristics of the beta titanium alloy.     

The effects of cholesterol-3-sulfate (CH-3S) on the phosphorylation of human C3a (hC3a) in vitro and on the ability of hC3a to induce vascular permeability in rats

The phosphorylation of human C3a (hC3a, anaphylatoxin) by two distinct protein kinases (PKA and CK-I) and the effect of cholesterol-3-sulfate (CH-3S) on this phosphorylation were biochemically investigated in vitro. It was found that (i) hC3a functions as a phosphate acceptor for PKA and CK-I, but not for CK-II; (ii) the CK-I-mediated phosphorylation of hC3a requires the presence of 3 microM CH-3S in a manner similar to the phosphorylation of HMG1 (CH-3S-binding protein) by CK-I; and (iii) CH-3S inhibits the PKA-mediated phosphorylation of hC3a in a dose-dependent manner (ID50=approximately 2 microM). As expected, hC3a containing high levels of Arg- and Lys-residues stimulated approx. 3-fold CK-II activity (phosphorylation of alpha-casein) in vitro. However, no significant effect of hC3a on CK-II activity was observed when hC3a was preincubated with CH-3S or fully phosphorylated by PKA in vitro. Furthermore, preincubation of hC3a with CH-3S diminished the ability of hC3a to induce vascular permeability in rats. The results provided here suggest that (i) hC3a is a CH-3S-binding protein; and (ii) CH-3S functions as a potent inhibitor for its physiological activities, including phosphorylation by PKA and CK-I, in vitro.     

Fracture mechanisms of retrieved titanium screw thread in dental implant

Titanium and its alloy are increasingly attracting attention for use as biomaterials. However, delayed fracture of titanium dental implants has been reported, and factors affecting the acceleration of corrosion and fatigue have to be determined. The fractured surface of a retrieved titanium screw and metallurgical structures of a dental implant system were analyzed. The outer surface of the retrieved screw had a structure different from that of the as-received screw. It was confirmed that a shear crack initiated at the root of the thread and propagated into the inner section of the screw. Gas chromatography revealed that the retrieved screw had absorbed a higher amount of hydrogen than the as-received sample. The grain structure of a titanium screw, immersed in a solution known to induce hydrogen absorption, showed features similar to those of the retrieved screw. It was concluded that titanium in a biological environment absorbs hydrogen and this may be the reason for delayed fracture of a titanium implant.     

Ki-67 expression and prognosis for smokers with resected stage I non-small cell lung cancer

BACKGROUND: The cigarette smoking status of patients before surgery is an important prognostic factor in evaluation of stage I non-small cell lung cancer, and the proliferative activity of lung tumors is also related to the patient's prognosis. This study evaluates relationships between various clinicopathologic factors, including tumor proliferative activity and smoking status, and the patient's prognosis in stage I non-small cell lung cancer. METHODS: One hundred eighty-seven stage I adenocarcinoma and squamous cell carcinoma cases were evaluated. The patients underwent complete resection between 1988 and 1993 at Chiba University Hospital. Expression levels of Ki-67 nuclear antigen, p53 protein, and retinoblastoma protein were determined immunohistochemically, and postoperative survival rates for patients in the categories of clinicopathologic factors were estimated. RESULTS: The mean Ki-67 labeling index (LI) for all cases was 19.3%. Labeling index values were significantly higher in squamous cell carcinoma than in adenocarcinoma (p < 0.0001). Postoperative survival of adenocarcinoma patients was significantly related to the LI values and to the patient's smoking status (p = 0.0164 and 0.0268, respectively). The LI values were also related to smoking status and the extent of histologic differentiation (p = 0.0112 and p < 0.0001, respectively). For non-smoking adenocarcinoma patients, higher LI values were associated with abnormalities in p53 expression (p = 0.0048). Retinoblastoma protein abnormalities were not related to LI values. CONCLUSIONS: In smokers with stage I pulmonary adenocarcinoma, tumor proliferative activity and smoking status before surgery were important prognostic determinants. The LI values were related to several clinicopathologic factors.