Real-time monitoring of glutamate following fluid percussion brain injury with hypoxia in the rat

In the present study, extracellular glutamate (Glu) was monitored in real time using an enzyme electrode biosensor following traumatic brain injury (TBI) either with or without inducing hypoxia in the rat. We also measured the cortical contusion volume at 3 days after insult by staining with 2,3,5-triphenyltetrazolium chloride (TTC). Male Sprague-Dawley rats (300-400 g) were anesthetized and then subjected to lateral fluid percussion (FP) brain injury of moderate severity (3.5-4.0 atm), using the Dragonfly device model (no. HPD-1700). The experimental animals were divided into four groups. Group 1 (n = 10) was subjected to TBI only, group 2 (n = 10) to TBI followed by 20 min of moderate hypoxia (FiO2: 10%), group 3 (n = 4) to 20 min of moderate hypoxia without TBI, and group 4 (n = 4) to sham. Seventy-two hours after the insults, the animals were sacrificed, their brains were stained with TTC, and the lesion volumes were calculated. A surge in the extracellular Glu concentration occurred immediately after TBI in groups 1 and 2. There was no significant difference between the two groups. Group 2 showed a prolonged efflux of Glu during hypoxia ( < 0.05). In group 3, Glu continued to show a mild increase. The cortical contusion volume in group 2 was significantly larger than that in group 1. To evaluate the possible involvement of apoptosis in groups 1 and 2, separate rats were sacrificed under the same procedures after 1, 6, 24, and 72 h after insult (n = 2/group). Immunohistochemical analysis demonstrated an increased number of both the cysteine protease caspase-3-positive cells at 24 h and TUNEL-positive cells at 72 h in group 2. These results suggest that TBI with moderate hypoxia induced the prolonged efflux of Glu, which thus resulted in more cortical damage due to necrosis and apoptosis.     

Response of quiescent and total tumor cells in solid tumors to neutrons with various cadmium ratios

Purpose: Response of quiescent (Q) and total tumor cells in solid tumors to neutron irradiation with three different cadmium (Cd) ratios was examined. The role of Q cells in tumor control was also discussed.Methods and Materials: C3H/He mice bearing SCC VII tumors received continuous administration of 5-bromo-2′-deoxyuridine (BrdU) for 5 days using implanted mini-osmotic pumps to label all proliferating (P) cells. Thirty minutes after intraperitoneal injection of sodium borocaptate-¹⁰B (BSH), or 3 h after oral administration of dl-p-boronophenylalanine-¹⁰B (BPA), the tumors were irradiated with neutrons, or those without ¹⁰B-compounds were irradiated with gamma rays. This neutron irradiation was performed using neutrons with three different cadmium (Cd) ratios. The tumors were then excised, minced, and trypsinized. The tumor cell suspensions were incubated with cytochalasin-B (a cytokinesis-blocker), and the micronucleus (MN) frequency in cells without BrdU labeling (Q cells) was determined using immunofluorescence staining for BrdU. The MN frequency in total (P + Q) tumor cells was determined from tumors that were not pretreated with BrdU. The sensitivity to neutrons was evaluated in terms of the frequency of induced micronuclei in binuclear tumor cells (MN frequency).Results: Without ¹⁰B-compounds, the MN frequency in Q cells was lower than that in the total cell population. The sensitivity difference between total and Q cells was reduced by neutron irradiation. Relative biological effectiveness (RBE) of neutrons compared with gamma rays was larger in Q cells than in total cells, and the RBE values for low-Cd-ratio neutrons tended to be larger than those for high-Cd-ratio neutrons. With ¹⁰B-compounds, MN frequency for each cell population was increased, especially for total cells. This increase in MN frequency was marked when high-Cd-ratio neutrons were used. BPA increased the MN frequency for total tumor cells more than BSH. Nevertheless, the sensitivity of Q cells treated with BPA was lower than that in BSH-treated Q cells. This tendency was clearly observed in high-Cd-ratio neutrons.Conclusion: From the viewpoint of enhancing the Q-cell sensitivity, tumors should be irradiated with high-Cd-ratio neutrons after BSH administration. However, normal tissue reaction remains to be examined because of its low tumor-to-normal tissue and tumor-to-blood biodistribution ratios.     

The local spread of lower bile duct cancer: evaluation by thin-section helical CT

This study illustrates the local spread of lower bile duct cancer with thin-section helical CT in correlation with the surgical and pathological findings. Pathologically, 16 patients had pancreatic invasion, 4 had small bowel mesentery invasion, 7 had extrapancreatic nerve plexus invasion, and 3 patients had vascular invasion. On thin-section helical CT, pancreatic invasion was correlated to the clarity or non-clarity of the bile duct mass-pancreas border and the presence of an intrapancreatic mass. Cases with small bowel mesentery and extrapancreatic nerve plexus invasion showed mass or stranding around the superior mesenteric artery and/or inferior pancreatoduodenal artery. Vascular invasion was seen as tumor contiguity to these vessels. Received: 28 September 1998; Revised: 30 December 1998; Accepted: 2 April 1999     

Early Experiences of Haemostasis on Brain Tumour Surgery with Argon Plasma Coagulation (APC)

Summary  Objective. We first applied a novel haemostatic strategy involving Argon Plasma Coagulation (APC), an innovative no-touch electrocoagulation technique in which a high-frequency alternating current is delivered to the tissue through ionized argon gas, to brain tumour surgery, and report its usefulness and limitations.  Methods. The APC system we used comprised an APC 300 developed by ERBE Elektromedizin GmbH, Germany. We applied APC to 13 brain tumours in 12 patients (5 meningiomas, 4 sarcomas, 2 glioblastomas, and 2 pituitary adenomas). To avoid unnecessary thermal injury to the tissue as much as possible, power/gas flow settings of 20 and 40 W were used. The impact time was varied individually but was around several seconds per one impact. The argon jet (1.5–4.5 L/min) clears a field of pooled blood and evenly conducts electrical energy to the target tissue. A thin and flexible probe particularly increased the usefulness of APC for haemostasis on deep-seated skull base tumour operations under a microscope.  Conclusion. All patients were successfully treated and satisfied with the surgical results without any complications due to APC. APC appears to be an excellent alternative strategy for achieving haemostasis on vascular-rich brain tumour surgery, and may be valuable for the management of patients with coagulation defects.     

Spontaneous closure of ventricular septal defects followed up from <3 months of age

BACKGROUND: This study evaluates the incidence and timing of spontaneous closure (SC) of ventricular septal defect (VSD) using Doppler color flow mapping. METHODS: A total of 225 infants (mean age 30 days) were diagnosed with uncomplicated VSD: 31 (14%) subpulmonary VSD, 159 (70%) perimembranous, and 35 (16%) muscular. The patients were divided into two groups according to the presence or absence of congestive heart failure (CHF). SC was confirmed with color Doppler. RESULTS: Surgical closure was performed in 59 patients (26%). SC occurred in 107 patients (48%); three (10%) of 31 with subpulmonary VSD, 75 (47%) of 159 with perimembranous VSD, and 29 (83%) of 35 with a muscular VSD. Average age at SC was 19 months. In three SC patients with a subpulmonary VSD, there was no aortic valve prolapse and no aortic regurgitation. SC occurred in 96% of SC patients with a perimembranous VSD by the age of 6 years, and in 93% of those with a muscular VSD by the age of 3 years. In patients without CHF, the rate of SC was 72%; 23% in subpulmonary VSD, 74% in perimembranous, and 85% in muscular. SC occurred in only 23% of patients with a perimembranous VSD with CHF. Mean age at the final examination was 6.9 years in 59 patients with a VSD remaining open, and 63% of patients with a perimembranous VSD remaining open had an aneurysm of the ventricular membranous septum. CONCLUSIONS: The SC rate of VSD by mean age of 6.9 years was 48%, but it was 72% in patients without CHF. In patients with CHF, SC was seen only in patients with a perimembranous VSD. The rate of SC was 10% in subpulmonary VSD. The authors contend that SC probably occurred by growth of muscular septum surrounding VSD. Muscular VSD spontaneously closed earlier than perimembranous VSD.     

Glial-derived growth factor signaling pathway in infantile hypertrophic pyloric stenosis

BACKGROUND/PURPOSE: Glial-derived growth factor (GDNF), which is the ligand of RET is reported to be essential for the development of enteric nervous system. A GDNF knockout mouse model has shown that the gastric region is a critical passing site between GDNF-RET-independent neuroblasts (colonizing the esophagus) and GDNF-RET-dependent neuroblasts (colonizing the small and large bowel). The earliest GDNF site of production is the mesenchyme and the outer smooth muscle cell (SMC) layer of the developing bowel. In the mature gastrointestinal tract the presence of GDNF is restricted to enteric glial cells. The aim of this study was to investigate the expression of GDNF and RET in infantile hypertrophic pyloric stenosis (IHPS). METHODS: Full-thickness muscle biopsy specimens were obtained from 8 IHPS patients at pyloromyotomy and from 8 age-matched controls without gastrointestinal disease. Indirect immunohistochemistry was performed using avidin-biotin-peroxidase complex method with anti-GDNF and anti-RET antibodies. Quantitative analysis was performed using sandwich-type enzyme-linked immunosorbent assay (ELISA) for GDNF. RESULTS: GDNF- and RET-positive nerve fibers were absent or markedly reduced in IHPS compared with controls. GDNF was expressed strongly by smooth muscle cells of both muscular layers in IHPS, whereas no GDNF expression was detected in pyloric muscle of controls. The quantity of total GDNF in IHPS was significantly higher than in controls (P < .01). CONCLUSIONS: The lack or markedly decreased number of GDNF-positive nerve fibers in IHPS supports the hypothesis of a selective immaturity of the enteric glia in the muscular layers in IHPS. The strong expression of GDNF in smooth muscle cells in IHPS and the increased levels of GDNF in IHPS suggest a compensatory mechanism by which the smooth muscle cells continue to produce GDNF until maturation of the enteric glial cells occurs.