SN-38 induces cell cycle arrest and apoptosis in human testicular cancer

OBJECTIVE: CPT-11 is one of the most widely used camptothecin analogues and is converted to form the active metabolite SN-38. Clinical trials are ongoing to better characterize its spectra of clinical activity, to determine the optimal schedules of administration, and to define the usage in combination with other chemotherapeutic compounds. MATERIALS AND METHODS: KU-MT, an AFP-producing testicular carcinoma cell line, was exposed to SN-38, etoposide, or cisplatin for 24 h, and the resulting cytotoxicity was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazonium bromide (MTT) assay. This paper describes the effects of SN-38 on the cell proliferation and cell cycle of testicular tumor cells in culture. RESULTS: SN-38 was shown to inhibit KU-MT cell growth more potently than either etoposide or cisplatin. A marked decrease in the percentage of S phase cells was accompanied by the enhancement of cyclin E levels. In concentrations of >30 nmol/l, SN-38 arrested the cell cycle in G2 and induced cell death via apoptosis. The apoptosis was promoted by Bax and p53 protein, which were both shown to be present by flow cytometric and Western blot analyses. CONCLUSION: These results suggest that CPT-11, a pro-drug of SN-38, may be clinically useful for the treatment of testicular cancer, and that the mechanism of this agent's cytotoxicity consists of cell cycle arrest and concomitant apoptosis.     

Neuronal expression of αB crystallin in cerebral infarction

alphaB crystallin (alphaBC) is one of the heat shock proteins that are induced under stressful conditions. In normal brains, alphaBC is present in oligodendrocytes and astrocytes, but not in neurons. Neuronal alphaBC expression in the central nervous system under pathological conditions has been investigated in several previous studies, most of which dealt with various neurodegenerative diseases with and without ballooned neurons. Neuronal expression of alphaBC has seldom been studied in cerebral infarction (CI), and the frequency of alphaBC-positive neurons in the various stages of CI is unknown. To investigate this issue, we examined 48 autopsy brains of patients with CI, and found neuronal expression of alphaBC in 68.8% of the cases. We found three types of alphaBC-positive neurons: normal morphological, convex, and ballooned neurons. Although alphaBC-positive neurons were present in the every stage of CI, they were more frequent later than 10 days after the onset of CI, and the frequency of alphaBC-positive ballooned neurons was particularly increased in the later stages of CI. This may indicate that morphologically normal neurons gradually swelled up through convex neurons, finally forming ballooned neurons. Previous studies indicated that alphaBC might have a cytoprotective function as a molecular chaperone, and we speculate that alphaBC is expressed in neurons subjected to ischemic stress, and exerts a cytoprotective effect on the neurons.     

Pulmonary artery stenting for recurrent lung cancer after left pneumonectomy

We present a case of a patient with stenosis of the pulmonary artery which was successfully treated by implantation of a vascular endoprosthesis. A 50-year-old man underwent left pneumonectomy for lung cancer. Eleven months later, a computed tomographic scan revealed a soft tissue mass in the mediastinum and there was severe stenosis of the remaining right main pulmonary artery. A self-expandable vascular endoprosthesis was implanted in the stenotic portion. We used percutaneous cardiopulmonary support (PCPS) during the procedure. We recommend the technique of pulmonary artery stenting using PCPS as efficacious and safe.     

Outcome measures of interepisode bipolar patients in a Turkish sample

Background We aimed to study the correlations of several outcome measures in bipolar patients with the clinical features of interepisode period. Methods Bipolar patients who were diagnosed according to DSM-III-R or IV were contacted and asked for a further evaluation. Interepisode bipolar patients (n = 100) were interviewed with the Schedule for Affective Disorders and Schizophrenia (SADS). In addition the Brief Disability Questionnaire (BDQ), the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and the Global Assessment Scale (GAS) were administered to assess outcome. They were also asked to check the List of Life Events (LLE) for the last six months. Results Our results can be summarised as follows: (1) quality of life was predicted by current subthreshold depressive symptoms; (2) the number of previous depressive episodes, current subthreshold depressive and manic symptoms predicted disability; (3) the number of previous depressive episodes and the duration of hospitalisation as well as current subthreshold depressive and manic symptoms predicted overall functioning; (4) the number and distress level of life events were correlated with suicidal symptoms. Conclusions Our findings suggest that outcome measures were correlated with subsyndromal disorder, the number of previous depressive episodes and the duration of hospitalisation. Accepted: 2 October 2001     

Time-dependent contribution of the hippocampal complex when remembering the past: a PET study

Previous studies of brain-damaged patients and functional neuro-imaging have consistently shown the importance of the hippocampal complex, i.e. the hippocampus and parahippocampal gyrus, in episodic memory retrieval. We wished to determine whether patterns of brain activation during memory retrieval as measured by PET are same or different when the oldness of a to-be-retrieved episode is manipulated. Using cue words, subjects remembered related episodes from three periods of their life, childhood, adolescence and recent period. The results showed an increase of parahippocampal activities during recall of episodes from childhood and recent period, but not from adolescence. These data suggest a possibility of time-dependent hippocampal contribution in episodic recall, which cannot be understood in simple terms of recent remote memory dichotomy.     

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.