Production of vascular endothelial growth factor in T-cell prolymphocytic leukemia

We describe a 79-year-old man who had massive pleural effusion and a proliferation of prolymphocytic leukemia cells in the peripheral blood, bone marrow, and pleural effusion fluid. Immunophenotyping of leukemia cells revealed either CD3+CD4+CD8-CD25+ or CD3+CD4+CD8+CD25+. The antibody against human T-cell lymphotropic virus type I was negative. A diagnosis of T-PLL was made. The level of VEGF in the plasma or pleural effusion fluid was very high. Moreover, polymerase chain reaction analysis demonstrated an expression of VEGF mRNA in the leukemia cells, indicating a production of VEGF from leukemia cells and its involvement in the pathogenesis of T-PLL.     

Neuroendocrine carcinoma of the prostate effectively treated by cisplatin and irinotecan--a case report

A 79-year-old man was referred to our hospital with urinary retention in August 2004. Because the serum PSA was 2,9 39 ng/mL,we performed transabdominal prostatic needle biopsy. Pathological examination of the prostate revealed conventional adenocarcinoma. CT scans and MRI showed a huge mass and lymph node metastasis. He was treated with diethyl stilbestrol diphosphate,followed by maximal androgen blockade therapy,and the serum PSA level decreased favorably. Follow-up CT revealed prostate and lymph node metastasis were reduced, but liver metastases, measuring 45 x 34 mm and 28 x 24 mm, respectively, were newly recognized in February 2006. The NSE level was high at 88.5 ng/mL, so a percutaneous liver biopsy was performed,and pathological examination of the liver revealed metastatic prostate cancer which showed neuroendocrine differentiation. The treatment was changed to chemotherapy comprising cisplatin and irinotecan. After three courses of the chemotherapy,liver metastasis was reduced in CT scans.     

Progressive changes of white matter integrity in schizophrenia revealed by diffusion tensor imaging

Recent magnetic resonance imaging (MRI) studies using diffusion tensor imaging (DTI) have suggested reduced fractional anisotropy (FA) in the white matter (WM) of the brain in patients with schizophrenia. We tried to examine whether such reduction in FA exists and whether such changes in FA progress in an age-dependent manner in a Japanese sample of chronic schizophrenia. FA values were compared between 42 patients with chronic schizophrenia and 42 controls matched for age and gender, by using DTI with voxel-by-voxel and region-of-interest analyses. Correlations of FA values with age and duration of illness were examined. Patients with schizophrenia showed lower FA values, compared to controls, in the widespread WM areas including the uncinate fasciculi and cingulum bundles. A significant group-by-age interaction was found for FA in the WM, i.e., age-related reduction of FA was more pronounced in schizophrenics than in controls. A significant negative correlation between FA and duration of illness was also found in the WM. Our data confirmed decreased FA in schizophrenics, compared to controls in the widespread WM areas. Such decreased FA values in schizophrenia might be attributable, at least in part, to progressive changes after the onset of the illness.     

Postoperative reversible deterioration in a spinal dural arteriovenous fistula

This 61-year-old man presented with weakness and sensory disturbance in the legs. There was a spinal dural arteriovenous fistula (SDAVF) fed by the left sixth intercostal artery with dorsal perimedullary drainage. Surgical division of the perimedullary drainage led to rapid neurological improvement. However, on the second postoperative day he experienced transient deterioration of second neuron function in the left upper lumbar segment resulting in motor weakness of the proximal leg muscles, absence of the patellar deep tendon reflex and thigh pain. No radiological findings explaining this deterioration were obtained. He was treated conservatively and all segmental symptoms and signs subsided by the fifth postoperative day. Although the precise mechanisms underlying the dramatic but often reversible deterioration after radical SDAVF treatment remain to be determined, we postulate that this was attributable to postoperative segmental venous hemodynamic changes based on the neurological changes.     

Late infantile GM1 gangliosidosis with progressive dilatation of common bile duct and obstructive apnea--an autopsy case

We report a 5-year-old autopsy case of late infantile type of GM1 gangliosidosis,which developed rare respiratory and intestinal complications. Obstructive apnea by adenoidal hypertrophy was improved by adenoidectomy, but the right bronchus was compressed by hilar lymph node swellings. The lymph nodes could not be treated surgically because of her poor general condition. There was hyperplasia showing foamy histiocyte including mucopolysaccharide which demonstrated a vacuolar formation containing irregular arranged fibrillar material on electron microscopy. Cerebral atrophy progressed gradually, and epileptic apnea developed, which was intractable to all antiepileptic drugs administered. Glycolipid accumulation, showing membranous cytoplasmic body on electron microscopy, seemed to lead to neurodegeneration. Abdominal distension due to hepatosplenomegaly, common bile duct dilatation compressed by lymph node swelling of the caput pancreatis part, and enteroparalysis was uncontrolled. These findings suggest that severe glycolipid deposition in lymphoreticular organs can induce various complications in patients with late infantile type of GM1 gangliosidosis.     

Motor evoked potential mapping and monitoring by direct brainstem stimulation. Technical note

Motor evoked potentials (MEPs) by direct brainstem stimulation were generated during 12 neurosurgical operations performed in five posterior fossa tumors, six vertebrobasilar aneurysms, and an arachnoid cyst. The anterior aspect of the brainstem was exposed using a subtemporal approach (in six cases), a presigmoid approach (one case), or a lateral suboccipital approach (five cases). A train of five monopolar 5 to 25 mA pulses was then applied, and MEPs were recorded from the extremities. Motor evoked potentials were recorded in all patients (four mappings and seven monitorings) except in a 12-year-old child who underwent surgery for a posterior cerebral artery aneurysm. Although he experienced postoperative motor palsy, the aneurysm ruptured before electrodes could be placed. Two patients with postoperative motor palsy, one with a clival meningioma and one with a basilar trunk aneurysm, had shown significant decreases in MEP amplitude and even complete disappearance of MEPs during intraoperative brainstem stimulation. Motor evoked potentials elicited by direct brainstem stimulation seem to be an accurate neurophysiological monitoring method during operations around the anterior and lateral aspects of the brainstem.     

Histological examination of false positive tissue resection using 5-aminolevulinic acid-induced fluorescence guidance

Intraoperative 5-aminolevulinic acid (5-ALA)-induced fluorescence guidance for resection of malignant brain tumors was correlated with histological examination to investigate false positive findings in 42 patients with malignant glioma and six patients with metastatic brain tumor. Patients received a single 1 g oral dose of 5-ALA 2 hours before surgery. The tumor site was illuminated with a laser with a peak wavelength of 405 +/- 1 nm and output of 40 mW. Samples with strong fluorescence were obtained from the tumor bulk and samples with weak fluorescence from the tumor cavity. Fluorescence was observed in 36 of the 42 malignant gliomas and four of the six metastatic brain tumors. No tumor cells were found in fluorescent samples from six of the 36 malignant gliomas and all four metastatic brain tumors. Five of the six malignant gliomas were recurrent cases. Fluorescence was found in areas of peritumoral edema or inflammatory cell and reactive astrocyte infiltration. Intraoperative 5-ALA-induced fluorescence guidance is useful for the resection of initial malignant glioma since false positive results are rare, but only non-eloquent weak positive areas should be resected. In contrast, all weak positive areas of recurrent malignant gliomas must be resected. Weak positive areas of the peritumoral edema surrounding metastatic brain tumors should be removed carefully as false positive results are common.     

Duraplasty in the posterior fossa using a boat-shaped sheet of expanded polytetrafluoroethylene

Application of sutures between expanded polytetrafluoroethylene (ePTFE) dural substitutes and the dura mater is often frustrating in posterior fossa surgery because of the difficulty in holding the elastic graft in a deep and narrow field. To resolve this problem, we have developed a boat-shaped graft made from a triangular ePTFE sheet by pinching each angle using a suture. Formation of standing edges of the sheet facilitates holding of the flaps for secure and more rapid suturing than the conventional approach using a flat sheet.     

Mechanism of cell cycle arrest and apoptosis induction by conjugated eicosapentaenoic acid, which is a mammalian DNA polymerase and topoisomerase inhibitor

Conjugated eicosapentaenoic acid (cEPA) selectively inhibited the activities of mammalian DNA polymerases (pols) and human DNA topoisomerases (topos). cEPA inhibited the cell growth of two human leukemia cell lines, NALM-6, which is a p53-wild type, and HL-60, which is a p53-null mutant, with LD50 values of 37.5 and 12.5 microM, respectively. In both cell lines, cEPA arrested in the G1 phase, and increased cyclin E protein levels, indicating that it blocks the primary step of in vivo DNA replication by inhibiting the activity of replicative pols rather than topos. DNA replication-related proteins such as RPA70, ATR and phosphorylated-Chk1/2 were increased by cEPA treatment in the cell lines, suggesting that cEPA led to DNA replication fork stress inhibiting the activities of pols and topos, and the ATR-dependent DNA damage response pathway could respond to the inhibitor of DNA replication. The compound induced cell apoptosis through both p53-dependent and p53-independent pathways in cell lines NALM-6 and HL-60, respectively. These results suggested the therapeutic potential of cEPA as a leading anti-cancer compound that inhibited activities of pols and topos.