A state of delirium (confusion) following cerebral angiography with ioxilan: a case report

The case of a 21-year-old man in a state of delirium (confusion) following cerebral angiography with 50 ml of ioxilan is reported. The patient was admitted to our hospital with facial hemangioma. After the examination, he complained of nausea and headache, and then became confused. No lesion was demonstrated on CT or MRI. About 3 days later, he recovered completely without any neurologic deficit. This patient had undergone cerebral angiography with ioxilan one year previously.     

Proton MR spectroscopic and diffusion tensor brain MR imaging in X-linked adrenoleukodystrophy: initial experience

PURPOSE: To compare conventional magnetic resonance (MR) imaging, proton MR spectroscopic imaging, and diffusion tensor (DT) MR imaging findings in patients with X chromosome-linked adrenoleukodystrophy (X-ALD). MATERIALS AND METHODS: Multisection proton MR spectroscopy and DT imaging were performed in 11 patients with X-ALD and in 11 healthy control subjects. Quantitative measures of N-acetylaspartate (NAA), choline, and creatine values and of isotropic apparent diffusion coefficient (IADC) and fractional anisotropy (FA) were obtained from coregistered regions of interest. DT imaging and metabolic parameters were compared by using regression analysis. In addition, differences in DT imaging and metabolite measurements between normal- and abnormal-appearing white matter on conventional MR images were evaluated by using a nonparametric (Mann-Whitney) test. RESULTS: A strong logarithmic relationship between NAA value and FA (r = 0.64, P <.001) and an inverse logarithmic relationship were found between NAA value and IADC (r = -0.69, P <.001). Creatine and choline values correlated poorly with IADC and FA. In the normal-appearing white matter of asymptomatic patients, the NAA value was 17% lower than that in the healthy control subjects (P =.016), whereas no significant difference in DT imaging measures was seen in these regions. CONCLUSION: In patients with X-ALD, MR spectroscopic imaging can depict abnormalities in white matter that have a normal appearance on both conventional MR and DT images; this finding suggests that it may be the most sensitive technique for detecting early abnormalities of demyelination or axonal loss in patients with X-ALD.     

Low-intensity warfarin is ineffective for the prevention of PTFE graft failure in patients on hemodialysis: a randomized controlled trial

Polytetrafluoroethylene (PTFE) dialysis grafts in patients with end-stage renal disease (ESRD) are prone to thrombotic failure. The objective of this multicenter, randomized, double-blind, placebo-controlled clinical trial was to determine if warfarin reduces the risk of failure of PTFE dialysis grafts. Patients with ESRD and newly placed PTFE grafts were studied at community and academic dialysis centers in Southwestern Ontario. Patients were allocated to receive warfarin or matching placebo, with the warfarin administered to achieve a target INR of 1.4 to 1.9. Time to graft failure was the main outcome measure. A total of 107 patients (56 allocated to warfarin) were randomized. The time-to-event analysis revealed no significant difference in the likelihood of graft survival between the two groups (odds ratio, 1.76 in favor of placebo; 95% confidence interval, 0.72 to 4.34). Six major bleeds occurred in five patients allocated to warfarin compared with none in the patients who received placebo (P = 0.03). In conclusion, low-dose warfarin was associated with an excess of clinically important major bleeding in patients with ESRD enrolled in this study. Furthermore, low-intensity, monitored-dose warfarin does not appear to prolong PTFE graft survival.     

Analysis of interfractional set-up errors and intrafractional organ motions during IMRT for head and neck tumors to define an appropriate planning target volume (PTV)- and planning organs at risk volume (PRV)-margins.

BACKGROUND AND PURPOSE: To analyze the interfractional set-up errors and intrafractional organ motions and to define appropriate planning target volume (PTV)- and planning organs at risk volume (PRV)-margins in intensity-modulated radiotherapy (IMRT) for head and neck tumors. PATIENTS AND METHODS: Twenty-two patients with head and neck or brain tumors who were treated with IMRT were enrolled. The set-up errors were defined as the displacements of the coordinates of bony landmarks on the beam films from those on the simulation films. The organ motions were determined as the displacements of the coordinates of the landmarks on the images recorded every 3 min for 15 min on the X-ray simulator from those on the initial image. RESULTS: The standard deviations (SDs) of the systematic set-up errors (Sigma-INTER) and organ motions (Sigma-intra) distributed with a range of 0.7-1.3 and 0.2-0.8 mm, respectively. The average of the SDs of the random set-up errors (sigma-INTER) and organ motions (sigma-intra) ranged from 0.7 to 1.6 mm and from 0.3 to 0.6 mm, respectively. Appropriate PTV-margins and PRV-margins for all the landmarks ranged from 2.0 to 3.6 mm and from 1.8 to 2.4 mm, respectively. CONCLUSIONS: We have adopted a PTV-margin of 5mm and a PRV-margin of 3mm for head and neck IMRT at our department.     

Reflux-free cannula for convection-enhanced high-speed delivery of therapeutic agents

OBJECT: Clinical application of the convection-enhanced delivery (CED) technique is currently limited by low infusion speed and reflux of the delivered agent. The authors developed and evaluated a new step-design cannula to overcome present limitations and to introduce a rapid, reflux-free CED method for future clinical trials. METHODS: The CED of 0.4% trypan blue dye was performed in agarose gel to test cannula needles for distribution and reflux. Infusion rates ranging from 0.5 to 50 microl/minute were used. Agarose gel findings were translated into a study in rats and then in cynomolgus monkeys (Macacafascicularis) by using trypan blue and liposomes to confirm the efficacy of the reflux-free step-design cannula in vivo. Results of agarose gel studies showed reflux-free infusion with high flow rates using the step-design cannula. Data from the study in rats confirmed the agarose gel findings and also revealed increasing tissue damage at a flow rate above 5-microl/minute. Robust reflux-free delivery and distribution of liposomes was achieved using the step-design cannula in brains in both rats and nonhuman primates. CONCLUSIONS: The authors developed a new step-design cannula for CED that effectively prevents reflux in vivo and maximizes the distribution of agents delivered in the brain. Data in the present study show reflux-free infusion with a constant volume of distribution in the rat brain over a broad range of flow rates. Reflux-free delivery of liposomes into nonhuman primate brain was also established using the cannula. This step-design cannula may allow reflux-free distribution and shorten the duration of infusion in future clinical applications of CED in humans.     

Selective COX-2 inhibitor regulates the MAP kinase signaling pathway in human osteoarthritic chondrocytes after induction of nitric oxide

The purpose of this study was to examine the effect of cyclooxygenase-2 (COX-2) inhibitors on the mitogen-activated protein (MAP) kinase signaling pathway and synthesis of glucosaminoglycan after nitric oxide (NO) induction in articular human chondrocytes. After NO induction, the cells were divided into three groups that were treated with either ethanol (control); a selective COX-2 inhibitor (Celecoxib), or no additive, and evaluated. There were no differences in the effect of the selective COX-2 inhibitor on mitochondrial membrane potential or Annexin V levels. However, Celecoxib significantly decreased prostaglandin E2 (PGE2) production. Celecoxib also decreased the phosphorylation state of p38 and p44/42 of MAP kinase. The ratio of chondroitin-6 sulfate (C6S)/C4S was increased in response to the exposure to Celecoxib. Celecoxib did not affect apoptosis, but decreased the activation of MAP kinase in osteoarthritic chondrocytes after NO induction. NO-induced OA chondrocytes were associated with the p38 and the p44/42 MAPK signaling pathways, in a pathway that is distinct from PGE2-mediated apoptosis.     

Histologically unique case of combined small cell and squamous cell carcinoma in a polypoid bronchial tumor

Presented herein is a case of combined small cell and squamous cell carcinoma in a polypoid bronchial tumor, showing a histologically unique progression, in a 76-year-old Japanese man. A bronchofiberscopic examination revealed that the bronchus (left B3) was occluded by the polypoid tumor. Biopsies were performed, and the pathological diagnosis was poorly differentiated squamous cell carcinoma. The patient consequently underwent a left upper lung lobectomy. The surgical specimen was described as a 24 x 8 x 8 mm soft tumor, emanating from the bronchial wall (left B3). Histologically, the tumor had two distinct components: (i) nearly the entire tumor was composed of atypical small round cells, with a high nuclear-cytoplasmic ratio, in the lamina propria, under the basement membrane; and (ii) the surface of the tumor was composed of poorly differentiated squamous cell carcinoma that had proliferated primarily above the basement membrane but there was also some proliferation, seen as island-like formations, below the basement membrane. The histological diagnosis was combined small cell and squamous cell carcinoma. It was suspected that poorly differentiated squamous cell carcinoma, generated in the bronchial epithelium, had caused small cell carcinoma resulting from neuroendocrine differentiation during its invasion into the lamina propria.     

The role of selective COX-2 inhibitors in reactive oxygen species formation in osteosarcoma cells after X-ray irradiation

Selective inhibition of COX-2 is thought to prevent carcinogenesis in some malignant tumors. In this study, in an effort to enhance the effectiveness of osteosarcoma treatment, we investigated the effect of a selective inhibitor of COX-2, with or without irradiation. We also asked whether selective COX-2 inhibitors increase the effect of X-ray irradiation, with regard to reactive oxygen species (ROS) formation in an osteosarcoma cell line. Our results showed that the presence of COX-2 inhibitor without irradiation results in faint spots of ROS formation that do not appear in the absence of COX-2 inhibitor. However, COX-2 inhibitor did not induce ROS formation when combined with irradiation. Thus, radiotherapy with selective COX-2 inhibitions has limitations in the treatment of radioresistant osteosarcoma to obtain the effective achievement, it is indispensable to combine another agent in future studies.     

Vaccination with tumor cell lysate-pulsed dendritic cells augments the effect of IFN-beta gene therapy for malignant glioma in an experimental mouse intracranial glioma

Interferon-beta (IFN-beta) has been used as an antitumor drug against human glioma, melanoma and medulloblastoma since the 1980s. Recently, we developed a new gene therapy using the IFN-beta gene against malignant gliomas and then began clinical trials in 2000. Since stimulation of immune system was one mechanism of antitumor effect induced by IFN-beta gene therapy, we hypothesized that combination of IFN-beta gene therapy with immunotherapy might increase its effectiveness. In the present study, we tested whether combination therapy with IFN-beta gene therapy and immunotherapy using tumor cell lysate-pulsed dendritic cells (DCs) would increase the efficacy of IFN-beta gene therapy. In an experimental mouse intracranial glioma (GL261), which cannot be cured by either IFN-beta gene therapy or DC immunotherapy alone, IFN-beta gene therapy following DC immunotherapy resulted in a significant prolongation in survival of the mice. Moreover, when this combination was performed twice, 50% of treated mice survived longer than 100 days. Considering these results, this combination therapy may be one promising candidate for glioma therapy in the near future.