Effects of opening peritumoral syrinxes on motor evoked potentials during resection of an intramedullary spinal cord tumor--case report

A 29-year-old woman presented with mild tetraparesis caused by an intramedullary cervical cord tumor extending from the C-5 to C-6 levels associated with rostral and caudal syrinxes extending to the C-1 and C-7 levels. Transcranial motor evoked potential (MEP) monitoring was carried out during tumor resection using high-frequency repetitive electrical stimulation. When the rostral syrinx was opened, the MEP amplitude in the right upper limb suddenly decreased by about 50%. When the caudal syrinx was opened, the amplitude immediately recovered to the baseline. During dissection of the attachment of the tumor, the amplitude decreased again by 70%, and did not recover. The tumor was totally removed. The histological diagnosis was ependymoma. Postoperatively, motor weakness in the right arm deteriorated but gradually recovered. The initial loss of amplitude on opening of the rostral syrinx may have resulted from distortion of the intramedullary pressure that compromised function of the motor tract nearby. Opening of the caudal syrinx normalized the intramedullary pressure and allowed the MEP to recover. Intraoperative monitoring of MEPs is valuable in minimizing injury to corticospinal pathways, but care must be taken in evaluating changes in MEP. Intramedullary spinal tumors with associated syrinxes are not rare, so surgeons should realize that opening of a syrinx can lead to MEP changes.     

Imatinib therapy for patients with chronic myelogenous leukemia

Imatinib mesylate (imatinib), a selective inhibitor of BCR-ABL tyrosine kinase, has shown excellent efficacy in patients with chronic myelogenous leukemia (CML) in the chronic phase, however, it does not in those in the accelerated phase or blastic crisis. In patients with CML who have undergone allogeneic stem cell transplantation, imatinib has the capability to induce hematological and even molecular response, and provides a prolonged survival among those in the chronic and accelerated phases. It has been demonstrated that major cytogenic response is a surrogate marker for survival in cases receiving imatinib. It has also been demonstrated that a genome-wide cDNA microarray enables the prediction of sensitivity to imatinib. The acquired resistance in patients who failed to respond to imatinib seemed to be induced by several point mutations in the BCR-ABL gene, which were likely to affect the binding of imatinib with BCR-ABL. Polyclonal cells which harbor distinct mutations in a single patient seemed to be selected in vivo under the selective pressure of imatinib, indicating the rationale of combined treatment with other types of agents. Recently, SPIRIT (STI571 Prospective International Randomized Trials) have been conducted, in which the efficacy of imatinib monotherapy, and imatinib combined with interferon or cytarabine were compared. New agents which inhibit the signaling pathway related to BCR-ABL, such as adaphostin (NSC680410), farnesyltransferase inhibitor SCH66336, MAP kinase inhibitor PD184352, PD98059, U0126, and antibiotic geldanamycin, have shown excellent activity combined with imatinib in vitro.     

Capsular tension ring use in a patient with congenital coloboma of the lens

Cataract surgery was performed in a 63-year-old man with bilateral coloboma of the lens. There was no traumatic history, but the patient had lower zonule deficiency and zonular weakness in both eyes, leading us to suspect congenital coloboma of the lens. In the first eye having cataract surgery, it was impossible to rotate the cataractous lens and place the intraocular lens (IOL) centrally in the capsular bag because the lens capsule was not round. The second eye had similar problems, and capsular tension ring implantation improved cataract lens rotation and phacodonesis, enabling central IOL implantation in the capsular bag. The visual acuity recovered to 20/20 in both eyes. Capsular tension ring implantation can facilitate cataract surgery in coloboma of the lens, even in long-term and continuous lens capsule deformity.     

Initial expression of interferon alpha receptor 2 (IFNAR2) on CD34-positive cells and its down-regulation correlate with clinical response to interferon therapy in chronic myelogenous leukemia

In order to investigate the mechanism of interferon-alpha (IFNalpha) action in the treatment of chronic myelogenous leukemia (CML), we examined surface expressions of both type I interferon receptor 1 (IFNAR1) and 2 (IFNAR2) subunits on CD34-positive cells in bone marrow (BM) in a total of 57 CML patients. Initial cell-surface IFNAR2 expression at diagnosis assessed by flow cytometry widely distributed but showed overall significantly higher expression in CML patients when compared with normal controls. In 15 fresh patients who subsequently received IFNalpha therapy, IFNAR2 expression at diagnosis was significantly higher in cytogenetic good responders than in poor responders. Down-regulation of IFNAR2 expression during IFNalpha therapy was observed only in good responders but not in poor responders. In addition to protein level, both initial high IFNAR2c mRNA expression level and its down-regulation during IFNalpha therapy, in purified CD34-positive cells, were also observed only in good responders. In contrast to IFNAR2, cell-surface IFNAR1 expression was generally lower than IFNAR2, and correlation between either the pretreatment level or down-regulation of IFNAR1 and clinical response was not evident. With in vitro IFNalpha stimulation, CD34-positive cells showed down-regulations of cell-surface IFNAR2, and IFNAR1 to a lesser extent, in one good-responder patient, but not in one poor-responder patient. Serum soluble interferon receptor (sIFNR) was higher in untreated CML patients than in normal controls, without any correlation with clinical response to IFNalpha. Thus, the pretreatment protein and mRNA expression levels of IFNAR2 and their down-regulations during IFNalpha therapy correlate well with IFNalpha response in CML patients.     

Reduction of infarct volume and apoptosis by grafting of encapsulated basic fibroblast growth factor-secreting cells in a model of middle cerebral artery occlusion in rats

OBJECT: This study was conducted to evaluate the effects of grafting encapsulated basic fibroblast growth factor (bFGF)-secreting cells in rat brains subjected to ischemic injury. METHODS: Two cell lines were used for encapsulated grafting in this experiment, namely, a bFGF-secreting cell line established by genetic manipulation of baby hamster kidney (BHK) cells, and a naive BHK cell line. Forty-seven Sprague-Dawley rats were used in this experiment. The animals were divided into the following three groups: those receiving grafts of encapsulated bFGF-secreting cells (BHK-bFGF group); those with grafts of encapsulated naive BHK cells (naive BHK group); and those with no grafts (control group). The authors implanted encapsulated cells into the right striatum of host rats in the BHK-bFGF and naive BHK groups. Six days after grafting, the host and control animals underwent permanent right middle cerebral artery occlusion (MCAO) with an intraluminal suture procedure. The infarct volume was evaluated using 2,3,5-triphenyltetrazolium chloride staining and computerized image analysis 24 hours after MCAO. Fragmentations of DNA in the host brains were analyzed using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling 12 hours after MCAO. The authors found that the infarct volume in the BHK-bFGF group was reduced by approximately 30% compared with that in the naive BHK and control groups. In the ischemic penumbral area, the number of apoptotic cells in the BHK-bFGF group was significantly decreased compared with that in the other groups. CONCLUSIONS: The grafting of encapsulated BHK bFGF-secreting cells protected the brain from ischemic injury. Encapsulation and grafting of genetically engineered cells such as bFGF-secreting cells is thus thought to be a useful method for protection against cerebral ischemia.     

Antioxidant effects of phytosterol and its components

Phytosterol contained in vegetable oils is known to exert a hypocholesterolemic function. In the present study, the antioxidant effects of phytosterol and its components, beta-sitosterol, stigmasterol, and campesterol, against lipid peroxidation were examined by making a comparison with 2,2,5,7,8-pentamethyl-6-chromanol (PMC). It was found that these compounds exerted antioxidant effects on the oxidation of methyl linoleate in solution and its effect decreased in the order of: PMC > phytosterol approximately campesterol approximately beta-sitosterol > stigmasterol. Phytosterol also suppressed the oxidation and consumption of alpha-tocopherol in beta-linoleoyl-gamma-palmitoyl phosphatidylcholine (PLPC) liposomal membranes, the effects being more significant than dimyristoyl PC of the same concentration. Stigmasterol accelerated the oxidation of both methyl linoleate in solution and PLPC liposomal membranes in aqueous dispersions, which was ascribed to the oxidation of allylic hydrogens at the 21- and 24-positions. Taken together, the present study shows that phytosterol chemically acts as an antioxidant, a modest radical scavenger, and physically as a stabilizer in the membranes.     

Improvement in cognitive function after radical excision of an anterior skull base meningioma - a report of 2 cases.

It has been well documented that memory difficulties in patients with anterior skull base meningioma may improve after tumour resection. However, there have been few reports on studies where precise testing of cognitive function has been conducted before and after surgery. Here we report 2 cases of anterior skull base meningioma where 2 tests of cognitive function, the Wechsler adult intelligence scale-revised (WAIS-R) and the Wechsler memory scale-revised (WMS-R), were performed by the patient before and after surgical treatment. After the operation there was a dramatic increase in the performance IQ as measured by the WAIS-R. In addition, the scores for both the "Attention/Concentration" and the "Delayed Recall" subsets of the WMS-R scale improved. There were differences between the 2 patients in the length of time required for functional recovery and this was thought to be due to the tumour size and the age of the patient. The use of these scales would enable physicians who are treating patients with anterior skull base meningioma to assess the recovery time that is likely to be needed before full return of cognitive function after surgery.     

Development of orally active nonpeptidic inhibitors of human neutrophil elastase

5-Amino-2-phenylpyrimidin-6-ones, some of their desamino derivatives, and miscellaneous derivatives were synthesized and biologically evaluated on both in vitro activity and oral activity in an acute hemorrhagic assay. These compounds contained an alpha-keto-1,3,4-oxadiazole moiety to bind covalently to the Ser-195 hydroxy group of human neutrophil elastase (HNE). Among those tested, compounds 11a-c,e,i-l(F), 11d,e,k(H), 21d,e,k(F), and 21d,e(H) showed a good oral profile. RS-Mixture 3(H) was selected for clinical evaluation based on its oral potency, duration of action, enzyme selectivity, safety profile, and ease of synthesis. Structure-activity relationships (SARs) are discussed.