Interstrain differences in susceptibility to liver carcinogenesis initiated by N-nitrosodiethylamine and its promotion by phenobarbital in C57BL/6NCr, C3H/HeNCrMTV- and DBA/2NCr mice

Selected inbred strains of mice were compared with respect totheir susceptibility to two-stage liver carcinogenesis. Five-week-oldmale mice of strains C57BL/6NCr (C57), C3H/HeNCr^MTV- (C3H) andDBA/2NCr (DBA) were given a single i.p. injection of N-nitrosodiethylamine(DEN, 90 mg/kg body weight) or the solvent tricaprylin (10 ml/kg).Beginning 2 weeks later, half of the DEN-treated and half ofthe control mice were given drinking water containing 0.05%phenobarbital (PB). Ten mice from each treatment group werekilled at 12, 24, 36 and 52 weeks of age (5, 17, 29 and 45 weeksexposure to PB). PB significantly increased both the numberof hepatocellular foci/cm² and the incidence of hepatocellulartumors after 17 weeks of treatment in 24-week-old DEN-initiatedmice of strains C3H (0.11 ± 0.07 versus 2.9 ±0.3 foci/cm² and 20 versus 70% incidence of hepatocellular tumors)and DBA (0.09 ± 0.09 versus 3.72 ± 0.6 foci/cm²and 0 versus 90% incidence of hepatocellular tumors) but wasineffective in C57 mice (0.04 ± 0.04 versus 0.07 ±0.07 foci/cm²). At 36 weeks of age the incidence of liver celltumors in mice given DEN but not PB was 10 (DBA), 10 (C57) and50% (C3H); the incidence was increased by PB to 90% in DBA and100% in C3H mice, but there was no increase in C57 mice. Evenat 52 weeks, the low incidence of hepatocellular tumors in C57mice given DEN only (20%) was not significantly increased bysubsequent exposure to PB. Serum PB levels observed at 12, 24and 36 weeks of age were significantly higher in DBA mice thanin C57 or C3H mice. Similar results were observed in a separatestudy in which PB was administered in drinking water to 7-week-oldmale mice of these three strains for 20 days, during which periodserum PB levels were measured at shorter intervals. DBA micethus appear to be unable to metabolize PB, which itself ratherthan its metabolites is probably responsible for tumor-promotingeffects. DBA mice were especially sensitive, while C57 micewere refractory to promotion of hepatocar-cinogenesis by PB.These two strains, which differ with respect to other significantparameters for chemical carcinogenesis including inducibilityfor aryl hydrocarbon hydroxylase and susceptibility to promotionof hydrocarbon-initiated skin tumors by 12-O-tetradecanoyl-phorbol-13-acetate,thus also provide a means for analysis of the pharmacogeneticsof susceptibility to hepatocellular tumor promotion.     

Prediction of hepatic clearance and availability by cryopreserved human hepatocytes: an application of serum incubation method.

A novel and convenient method was established for the prediction of in vivo metabolic clearance in human liver. The present method applied the in vitro-in vivo extrapolation paradigm previously established in rats to the in vitro data obtained from cryopreserved human hepatocytes. Predicted hepatic availability and clearance were compared with the reported oral bioavailability and plasma clearance in humans for 14 clinically used drugs (naloxone, buspirone, verapamil, lidocaine, imipramine, metoprolol, timolol, antipyrine, diazepam, quinidine, caffeine, propranolol, diclofenac, and phenacetin). A large interindividual variation was observed in the intrinsic metabolic clearance among separate cryopreserved preparations from different subjects. The prediction generally resulted in a marked underestimation when the biologically based scaling factor (3.1 x 10(9) cells/kg) was used for the extrapolation of in vitro data (milliliters per minutes per cells) to in vivo value (milliliters per minutes per kilograms). Reasonably good in vitro-in vivo correlations were obtained with empirically calculated scaling factors, 8.5 x 10(9) (cells/kg) from 10 individual preparations and 10.8 x 10(9) (cells/kg) from pooled preparation of two selected lots, which were 3- to 4-fold larger than the biologically based scaling factor. These data suggested that the calibration of inherent interindividual variation of metabolic activities among different cryopreserved preparations of human hepatocytes to obtain the empirical scaling factor, which is applicable only to the preparation used, was an essential step for more reliable and quantitative prediction of in vivo metabolic activity in humans.     

Magnetic resonance imaging of intracranial venous angiomas

Magnetic resonance imagings (MRI) were made of intracranial venous angioma (six angiographically proved, four presumed). All draining veins were identified as a linear or a small round structure with a flow void. The stellate configuration was observed in seven of the ten patients. In two of the ten, the associated intraparenchymal hematoma was evident. Increased intensity of adjacent parenchyma on T2-weighted images was detected in four of ten patients, and a decreased intensity on the T1-weighted images was noted in three of eight. Thus, MRI is a pertinent diagnostic modality for evaluating intracranial venous angioma. Angiography does not seem to be required for confirmation in patients with typical MR findings.     

Vascular compression of the oculomotor nerve disclosed by thin-slice magnetic resonance imaging

Purpose: To describe the thin-slice magnetic resonance imaging features of vascular compressive oculomotor nerve paresis.Methods: We performed thin-slice (2 mm thick) magnetic resonance imaging of the brainstem in a 74-year-old woman with right partial oculomotor nerve paresis using spoiled gradient recalled acquisition in the steady state.Results: Thin-slice magnetic resonance images disclosed that the right oculomotor nerve was compressed and dislocated superiorly and laterally by the tortuous basilar artery. No other abnormalities were observed.Conclusion: This is the first case report of vascular compressive oculomotor nerve paresis disclosed by thin-slice magnetic resonance imaging.     

Multichannel near-infrared spectroscopy in depression and schizophrenia: cognitive brain activation study.

BACKGROUND: Recent developments in near-infrared spectroscopy (NIRS) have enabled the noninvasive clarification of brain functions in psychiatric disorders with measurement of hemoglobin concentrations as cerebral blood volume. METHODS: Ten patients with depression, 13 patients with schizophrenia, and 16 age- and gender-matched healthy control subjects participated in the study after giving consent. The relative concentrations of oxyhemoglobin [oxyHb] were measured with frontal and temporal probes every.1 sec during word fluency and unilateral finger tapping tasks, with two 24-channel NIRS machines. RESULTS: The [oxyHb] increase patterns during the word fluency task varied among the three groups, although their task performances were similar: the depression group was characterized by a smaller [oxyHb] increase during the first half of the task period and the schizophrenic group by a small trough of [oxyHb] at the start of the task period and [oxyHb] re-increase in the posttask period. [OxyHb] increases during the finger-tapping task were rather larger in the patient groups than in the control group. CONCLUSIONS: The characteristic time courses of [oxyHb] changes in the frontal lobe were elucidated for depression and schizophrenia. Near-infrared spectroscopy, with its noninvasiveness and high time resolution, can be a useful tool for research and clinical purposes in psychiatry.     

Effect of periarticular and intraarticular lidocaine injections for sacroiliac joint pain: prospective comparative study

Background The sacroiliac joint (SIJ) can be a source of low back pain. Previous studies indicated that SIJ pain could originate from both the joint capsule and the posterior ligamentous tissues. It has not been clarified as to whether an intraarticular or periarticular injection procedure is more effective for this type of pain. The purpose of this study was to evaluate the effect of two injection procedures prospectively. Methods After a pain provocation test, an intraarticular injection of local anesthetic (2% lidocaine) was performed on the first 25 consecutive patients with SIJ pain and a periarticular injection on another 25. The periarticular injections were given to one or more sections of the posterior periarticular area of the SIJ and to another section in the extracranial portion. The effect of these injections was assessed using the “restriction of activities of daily life” scoring system from the Japanese Orthopaedic Association. Results The periarticular injection was effective in all patients, but the intraarticular one was effective in only 9 of 25 patients. An additional periarticular injection was performed in 16 patients who experienced no effect from the initial intraarticular injection and was considered effective in all of them. The injection into the middle of the periarticular area was more effective for SIJ pain. The improvement rate after the periarticular injection was 96%, which was significantly higher than that after the intraarticular injection, which was 62%. Conclusions For patients with SIJ pain, periarticular injection is more effective and easier to perform than the intraarticular injection and should be tried initially.     

Defecographic assessment after colonic J pouch-anal anastomosis

Colonic J pouch anal anastomosis is widely employed after rectal resection. In the 36 patients who participated in our retrospective study, although postoperative continence was retained/maintained in each individual, a survey questionnaire indicated some difficulties in neoanorectal function. Therefore, defecography was performed in 20 of these patients. Patients experiencing soiling were found to have an increased ano-pouch angle and pelvic floor descent. Loss of sensation and incomplete evacuation were also associated with an abnormally large pelvic floor descent. However, stool frequency, urgency, and the need for medication showed no correlation with any of the defecography parameters. These findings thus suggested that the puborectal muscle and the levator ani muscle played an important role in postoperative function. Defecography was also found to provide a dynamic assessment of the postoperative state of colonanal reconstruction.     

Spinal cord herniation into pseudomeningocele after traumatic nerve root avulsion: case report and review of the literature

We present an extremely rare case of traumatic spinal cord herniation due to a brachial plexus avulsion injury and provide a review of the literature of spinal cord herniation. Spinal cord herniation is an uncommon condition that can occur spontaneously or as a result of surgery or trauma. This condition often presents with symptoms and signs as Brown-Séquard syndrome. Traumatic pseudomeningoceles after a brachial plexus avulsion injury have been reported. But transdural herniation of the spinal cord into this pseudomeningocele is an extremely rare and poorly documented condition. There is only two reports of this condition in a thoracic case. The authors report the case of a 22-year-old man presented with a 2-year history of quadriplegia. He was involved in a motorcycle accident, 3 years prior to his presentation. Four years after the initial right brachial plexus injury, he was not able to walk independently. Magnetic resonance imaging (MRI) and computerized tomography (CT) myelography revealed a lateral pseudomeningocele arising from the right C6–7 and C7–T1 intervetebral foramen and cervical spinal cord herniation into this pseudomeningocele. The patient underwent primary closure of pseudomeningocele to prevent spinal cord reherniation. He can walk with cane and use left arm unrestrictedly at the 2-year follow-up examination. Spinal cord herniation following traumatic nerve root avulsion is extremely rare but it should be considered in the differential diagnosis of patients presenting with delayed myelopathy or Brown-Séquard syndrome.