Accumulation of L-[2-(F-18)]fluorophenylalanine in peri-infarct area in a patient with acute cerebral infarction

We studied the brain uptake of amino acid in a patient with acute cerebral infarction with L-[2-(F-18)] fluorophenylalanine and positron emission tomography. The increased accumulation of the ligand was specifically found in the peri-infarct area where oxygen metabolism was still maintained but decreased later in the 72-day follow-up period. The kinetic analysis revealed that increased accumulation was not due to increased transport from the blood to the brain but to delayed washout from the brain to the blood. Although the mechanism is still unknown, abnormally high accumulation of L-[F-18]fluorophenylalanine may predict delayed neuronal changes after ischemic insults of the brain.     

Neurotoxicity and pharmacokinetics of ventriculolumbar perfusion of methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-gluco-pyranoside (MCNU) in dogs

Summary Ventriculolumbar perfusion of methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU), a water soluble nitrosourea with log P-0.71, may be efficacious in the treatment of subarachnoid dissemination of malignant glioma. We used 2 dogs to study the neurotoxicity and pharmacokinetics of MCNU. MCNU (1 mg), dissolved in 10 ml of artificial CSF, was administered via the right lateral ventricle during a period of 18 to 42 min and the CSF was drained by lumbar puncture. The perfusion was repeated once a week for 10 consecutive weeks. No neurological and systemic symptoms were noted after perfusion. Histological examination of the brain and spinal cord showed local denudation of the ependyma and local subependymal spongy degeneration and gliosis in the lateral ventricle into which MCNU was administered in one dog and local denudation of the ependyma in the other. When administration was over a period of 21 to 38 min, the MCNU concentration in the lumbar CSF peaked at 11.11 to 50.67 g/ml, in 28 to 78 min. The area under the drug concentration-time curve (AUC) was 1152 g×min/ml on average, significantly larger than that of ACNU. The elimination phase followed linear kinetics and the half-time was 41.1 min on average, significantly longer than that of ACNU. These findings suggest that ventriculolumbar perfusion of MCNU may be effective in the treatment of subarachnoid dissemination of malignant glioma notwithstanding some local histological changes.     

Predicting the viability of grafted livers in rats through a rapid and sensitive metabolic indicator assessed by 31P-NMR spectroscopy

The present study was undertaken to clarify whether a correlation exists between the hepatic ratio of the -phosphorous moiety of ATP (-ATP) to inorganic phosphate (Pi), measured by ³¹P nuclear magnetic resonance spectroscopy 1 h after the reestablishment of portal blood flow, and the survival rate of rats following liver transplantation. This ratio was compared with the arterial ketone body ratio [AKBR (acetoacetate/3-hydroxybutyrate)], which is accepted as a reliable indicator of liver viability. After the transplantation of fresh livers, the 1-week survival rate was 92% and the -ATP/Pi ratio was 64% of the normal level. When the liver grafts were subjected to warm ischemia for 25 min or 45 min prior to harvesting, the 1-week survival rate decreased to 43% and 0%, respectively, and the -ATP/Pi ratio dropped to 31% and 18% of the normal level, respectively. On the other hand, the AKBR was about 25% of the normal level after transplantation of fresh livers, while it was 37% and 48% after transplantation with 25 min and 45 min of warm ischemia, respectively. However, 4h after the reestablishment of portal blood flow, the AKBR correlated with the -ATP/Pi ratio in both the fresh graft group and the 45-min warm ischemic damage group. These results show that the -ATP/Pi ratio provides an accurate evaluation of a graft viability even at an extremely early stage following liver transplantation, and should prove useful for the early diagnosis of primary graft nonfunction after liver transplantation.     

Metastatic seeding of bile duct carcinoma in the transhepatic catheter tract: Report of a case

We describe herein the case of a 51-year-old woman in whom metastatic tumor seeding of the percutaneous transhepatic biliary drainage tract occurred following a pancreatoduodenectomy for carcinoma of the distal common bile, duct. An abdominal computed tomography scan done 6 months after the initial operation detected a hepatic lesion located at the site of the previous percutaneous transhepatic biliary drainage tract. Implantation of bile duct carcinoma in the drainage tract was diagnosed, and the recurrent tumor was successfully resected by performing a subsegmentectomy of segment 3 and removal of the adjacent abdominal wall. At present, 5 years and 4 months after the second resection, the patient is in good health without any signs of recurrence. This case report demonstrates that an aggressive surgical approach should be performed for tumor seeding of a transhepatic biliary catheter tract.     

Handlebar hernia with intra-abdominal extraluminal air presenting as a novel form of traumatic abdominal wall hernia: Report of a case

An 18-year-old male was admitted to our Emergency Department with a traumatic abdominal wall hernia (TAWH) of the left lower quadrant (LLQ) after suffering hypogastric blunt injury and urogenital lacerations in a motorcycle accident. Upright chest X-ray showed a small amount of right infradiaphragmatic free air, and a computed tomographic (CT) scan demonstrated an abdominal wall hernia. At surgery, no impairment was found in the digestive tract, and an abdominal herniorrhaphy was performed. It is suggested that the free air had passed through a connection between the scrotal laceration and the contralateral abdominal defect via the subcutaneous space and was palpated as emphysema. This is a new type of TAWH, which suggests that blunt abdominal trauma may result in negative pressure in the subcutaneous and peritoneal cavity, and this could reflect the pathophysiology of TAWH.     

Oxidative damage on DNA induced by asbestos and man-made fibers in vitro

Summary We compared the potential of asbestos and man-made fibers to attack DNA by the determination of the yield of 8-hydroxy-2-deoxyguanosine (8-OH-dGuo) under several in vitro conditions. Asbestos induced 6.6–99.8 of 8-OH-dGuo per 10⁵ dGuo in calf thymus DNA after 20 h of incubation, while the levels of 8-OH-dGuo in man-made fibers were low (3.6–9.4). The amounts of 8-OH-dGuo were strongly stimulated by the addition of H₂O₂ in asbestos, but not in man-made fibers. However, the yield of 8-OH-dGuo was induced more than that with asbestos by the further addition of FeSO₄ in attapulgite, fiberglass, potassium titanate whisker, and metaphosphate polymer. The addition of ethylene diamine tetraacetic acid (EDTA) promoted the induction of 8-OH-dGuo with asbestos and H₂O₂. The effects of mannitol (known as a hydroxy radical scavenger) were not dramatic on 8-OH-dGuo induction by all fibers except fiberglass and basic magnesium sulfate whisker, which induced higher amounts after mannitol addition than in these fibers and H₂O₂. Therefore, it was suggested that asbestos could damage DNA, resulting in 8-OH-dGuo as a cause of point mutation, and also several types of manmade fibers had similar effects to asbestos under certain conditions.     

Diagnostic reliability and significance of irregular beta patterns.

We designated EEGs with marked and irregular beta waves in basic patterns as "irregular beta patterns" on the basis that these patterns are related with particular symptoms such as dysphoria, irritability and autonomic symptoms and they implicate choice of therapeutic agents. Because of good response to antiepileptic agents in patients with "irregular beta patterns" along with EEG characteristics, we hypothesized that the prevalence of "irregular beta patterns" is higher in epileptics than in other psychiatric patients. In the present study, we tested this hypothesis, investigating actual frequencies of these patterns among different diagnostic categories for all patients whose EEG were recorded in all the first-visit patients to the Outpatient Clinic, Department of Neuropsychiatry of the Tokyo University Hospital during one year period of 1986. Before starting this investigation, we checked the interrater reliability for these patterns. Therefore, two studies are reported here. In Study 1, five raters judged 98 EEG recordings blindly (43 epileptics and 55 healthy subjects). As a result, the generalized Kappa of 0.473 was obtained, indicating our agreement level was moderate or fair. This result lends support to our contention that irregular beta patterns are reliably judged. In Study 2, we judged the EEG recordings (137 schizophrenics, 62 affective disorders, 43 epileptics and 55 healthy controls) and calculated the prevalence rate of "irregular beta patterns" among the diagnostic categories. The results show that the prevalence rates of "irregular beta patterns" among psychiatric disorders and normal controls were 13% (18/137) in schizophrenics, 11% (7/62) in affective disorders, 14% (6/43) in epileptics and 4% (2/55) in healthy controls. These rates did not differ significantly among the three disorders. Thus, our hypothesis was not supported. The clinical significance of these patterns is discussed.     

Role of cyclin E and p53 expression in progression of early gastric cancer

Background. To elucidate the role that cyclin E overexpression plays in the progression of early gastric cancer, we examined the expression of cyclin E and p53, as abnormal p53 expression is linked with cyclin E overexpression in exerting adverse affects on the cell cycle. Methods. Specimens from 108 early gastric cancers were stained by an immunohistochemical method, using anti-cyclin E and anti-p53 antibodies. Results. The positivity rate of cyclin E expression in early gastric cancer was 33% (36/108). Cyclin E-positive tumors invaded more deeply (P < 0.05), infiltrated lymphatic vessels more frequently (P < 0.01), showed a higher incidence of differentiated cancer (P < 0.01), and more often expressed p53 (P < 0.01) than cyclin E-negative tumors. Differentiated cancers showing coexpression of cyclin E and p53 were more likely to metastasize to the lymph nodes. Conclusions. Overexpression of cyclin E may promote the progression of early gastric cancer. Received for publication on Apr. 27, 1998; accepted on Nov. 17, 1998     

Pronounced synergistic promotion of N-bis(2-hydroxypropyl)nitrosamine-initiated thyroid tumorigenesis in rats treated with excess soybean and iodine-deficient diets.

We have reported that excess soybean treatment and iodine deficiency synergistically interact, resulting in remarkable induction of thyroid hyperplasias in rats. In the present study, modifying effects of excess soybean and iodine-deficient diets were investigated in the post-initiation phase of N-bis(2-hydroxypropyl)nitrosamine [DHPN]-initiated thyroid tumorigenesis in rats. AIN-93G in which casein was replaced with gluten was used as a basal diet to avoid possible iodine contamination. In Experiment 1, F-344 rats of both sexes were sc injected with DHPN at a dose of 2800 mg/kg body weight and then fed a diet containing 0%, 0.8%, 4%, or 20% defatted soybean for 12 weeks, with proportional replacement of gluten by soybean flour. Although no thyroid proliferative lesions were found in any group, the absolute thyroid weights were significantly (p < 0.01) elevated with the 20% soybean treatment. In Experiment 2, after similar sc injection of DHPN, rats were fed a basal diet or a diet containing 20% soybean under iodine normal or deficient conditions for 12 weeks. Soybean feeding to both sexes under iodine deficient but not normal conditions dramatically enhanced the development of thyroid follicular adenomas (p < 0.01) and adenocarcinomas (p < 0.05), in good agreement with decrease in thyroxine and increase in thyroid-stimulating hormone. Thus co-exposure to excess soybean and iodine deficiency results in synergistic promotion of DHPN-initiated thyroid tumorigenesis in rats, of which mechanisms appear to primarily involve effects on serum hormone levels.     

Label-free metabolic imaging of non-alcoholic-fatty-liver-disease (NAFLD) liver by volumetric dynamic optical coherence tomography

Label-free metabolic imaging of non-alcoholic fatty liver disease (NAFLD) mouse liver is demonstrated ex vivo by dynamic optical coherence tomography (OCT). The NAFLD mouse is a methionine choline-deficient (MCD)-diet model, and two mice fed the MCD diet for 1 and 2 weeks are involved in addition to a normal-diet mouse. The dynamic OCT is based on repeating raster scan and logarithmic intensity variance (LIV) analysis that enables volumetric metabolic imaging with a standard-speed (50,000 A-lines/s) OCT system. Metabolic domains associated with lipid droplet accumulation and inflammation are clearly visualized three-dimensionally. Particularly, the normal-diet liver exhibits highly metabolic vessel-like structures of peri-vascular hepatic zones. The 1-week MCD-diet liver shows ring-shaped highly metabolic structures formed with lipid droplets. The 2-week MCD-diet liver exhibits fragmented vessel-like structures associated with inflammation. These results imply that volumetric LIV imaging is useful for visualizing and assessing NAFLD abnormalities.