Impulse response function based on multivariate AR model can differentiate focal hemisphere in temporal lobe epilepsy

The purpose of this study is to propose and investigate a new approach for discriminating between focal and non-focal hemispheres in intractable temporal lobe epilepsy, based on applying multivariate time series analysis to the discharge-free background brain activity observed in nocturnal electrocorticogram (ECoG) time series. Five unilateral focal patients and one bilateral focal patient were studied. In order to detect the location of epileptic foci, linear multivariate autoregressive (MAR) models were fitted to the ECoG data; as a new approach for the purpose of summarizing these models in a single relevant parameter, the behavior of the corresponding impulse response functions was studied and described by an attenuation coefficient. In the majority of unilateral focal patients, the averaged attenuation coefficient was found to be almost always significantly larger in the focal hemisphere, as compared to the non-focal hemisphere. Also the amplitude of the fluctuations of the attenuation coefficient was significantly larger in the focal hemisphere. Moreover, in one patient showing a typical regular sleep cycle, the attenuation coefficient in the focal hemisphere tended to be larger during REM sleep and smaller during Non-REM sleep. In the bilateral focal patient, no statistically significant distinction between the hemispheres was found. This study provides encouraging results for new investigations of brain dynamics by multivariate parametric modeling. It opens up the possibility of relating diseases like epilepsy to the properties of inconspicuous background brain dynamics, without the need to record and analyze epileptic seizures or other evidently pathological waveforms.     

Isolated cranial neuropathy associated with anti-glycolipid antibodies

We describe seven patients with isolated cranial neuropathy in whom serum anti-glycolipid antibodies were detected. Trigeminal sensory neuropathy was found in four patients, who had exhibited symptoms for 2 months to 4 years. The other three patients showed facial nerve palsy with or without ophthalmoparesis. Temporal profile analysis of anti-glycolipid antibodies revealed that titers of anti-glycolipid IgM antibodies against GM2 and LM1 gradually decreased in patients having chronic trigeminal sensory neuropathy. In patients with acute trigeminal sensory neuropathy, elevation of anti-LM1 antibody titers continued over 12 months although anti-GalNAc-GD1a antibody disappeared. On the other hand, titers of anti-glycolipid antibodies rapidly decreased in patients with acute facial nerve palsy with or without ophthalmoparesis. We conclude that anti-glycolipid antibodies may play an important role in the development of isolated cranial neuropathy in some patients.     

Caspase 3-mediated focal adhesion kinase processing in human ovarian cancer cells: possible regulation by X-linked inhibitor of apoptosis protein

OBJECTIVE: Cell adhesion is an important cell survival determinant and disruption of integrin-mediated signal transduction may be involved in anchorage-dependent cell death. We have examined the processing of focal adhesion kinase (FAK), a component of integrin-mediated signal transduction, in a cisplatin-sensitive human ovarian epithelial cancer cell line (OV2008), to test the possible role of FAK degradation in the control of apoptosis via regulation of cell attachment. METHODS: FAK processing after cisplatin treatment in the absence or presence of various caspase-inhibiting substances was analyzed by Western blot. Caspase-inhibiting activities were introduced using cell-permeable peptides or adenoviral vector. RESULTS: Cisplatin-induced caspase 3 and FAK cleavage, cell detachment from the growth surface, and apoptosis in a temporally related and concentration-dependent manner. FAK fragments were detected exclusively in cells detached from the culture surface. Addition of active caspase 3 to the whole cell lysate elicited a similar pattern of FAK cleavage. Pretreatment of whole cell lysates and cells with tetrapeptide inhibitors of caspases significantly decreased FAK cleavage induced by exogenous active caspase 3 and cisplatin, respectively. Overexpression of X-linked inhibitor of apoptosis protein (Xiap), an endogenous caspase inhibitor, attenuated the cisplatin-induced FAK processing, morphologic changes, and apoptosis. The inhibitory action of Xiap was abolished with the deletion of a functional motif required for caspase inhibition. CONCLUSION: These findings are consistent with our hypothesis that FAK processing is in part mediated by caspase 3, the activation of which is modulated by Xiap.     

Ki16425, a subtype-selective antagonist for EDG-family lysophosphatidic acid receptors

Lysophosphatidic acid (LPA) exerts a variety of biological responses through specific receptors: three subtypes of the EDG-family receptors, LPA1, LPA2, and LPA3 (formerly known as EDG-2, EDG-4, and EDG-7, respectively), and LPA4/GPR23, structurally distinct from the EDG-family receptors, have so far been identified. In the present study, we characterized the action mechanisms of 3-(4-[4-([1-(2-chlorophenyl)ethoxy]carbonyl amino)-3-methyl-5-isoxazolyl] benzylsulfanyl) propanoic acid (Ki16425) on the EDG-family LPA receptors. Ki16425 inhibited several responses specific to LPA, depending on the cell types, without any appreciable effect on the responses to other related lipid receptor agonists, including sphingosine 1-phosphate. With the cells overexpressing LPA1, LPA2, or LPA3, we examined the selectivity and mode of inhibition by Ki16425 against the LPA-induced actions and compared them with those of dioctyl glycerol pyrophosphate (DGPP 8:0), a recently identified antagonist for LPA receptors. Ki16425 inhibited the LPA-induced response in the decreasing order of LPA1 >/= LPA3 > LPA2, whereas DGPP 8:0 preferentially inhibited the LPA3-induced actions. Ki16425 inhibited LPA-induced guanosine 5'-O-(3-thio)triphosphate binding as well as LPA receptor binding to membrane fractions with a same pharmacological specificity as in intact cells. The difference in the inhibition profile of Ki16425 and DGPP 8:0 was exploited for the evaluation of receptor subtypes involved in responses to LPA in A431 cells. Finally, Ki16425 also inhibited LPA-induced long-term responses, including DNA synthesis and cell migration. In conclusion, Ki16425 selectively inhibits LPA receptor-mediated actions, especially through LPA1 and LPA3; therefore, it may be useful in evaluating the role of LPA and its receptor subtypes involved in biological actions.     

Surgical-site infection surveillance at a small-scale community hospital

Surveillance of surgical-site infection (SSI) is becoming more important given the current situation of increasing antibiotic resistance by microorganisms. It may be difficult to carry out SSI surveillance at small-scale community hospitals because of small staff numbers. We examined whether SSI surveillance could be carried out with a system we devised. Furthermore, we investigated the SSI rateat our small-scale community hospital (179 beds) in aJapanese city (populations, 330 000). Between June andDecember 2003, operations were performed on 210patients. Procedures were identified as clean (n = 85),clean-contaminated (n = 108), contaminated (n = 14), or dirty-infected (n = 3). A 7-month prospective survey ofSSI was conducted. SSIs were classified according to the Centers for Disease Control and Prevention criteria and identified using bedside surveillance and post-discharge follow-up. SSI developed following 16 procedures (7.6%). All patients who developed SSI had received antibiotic prophylaxis. Among the 16 patients with SSI, operations were clean (n = 1), clean-contaminated (n = 8), contaminated(n = 5), or dirty-infected (n = 2). Enterobacteriaceae were the most frequently isolated microorganisms, followed by Pseudomonas aeruginosa. SSI surveillance is just as important at small community hospitals as it is at larger hospitals, and SSI surveillance is relatively simple to institute at small-scale community hospitals with the selective use of investigation items.     

Allodynia and hyperalgesia in adjuvant-induced arthritic rats: time course of progression and efficacy of analgesics

The complete Freund's adjuvant (CFA)-induced arthritic rat model has extensively served as a laboratory model in the study of arthritic pain. However, the time courses of allodynia and hyperalgesia and the efficacies of different analgesics have not fully been analyzed in this model. Mechanical allodynia, thermal and joint hyperalgesia, and other disease development parameters (body weight, mobility, paw volume, and joint stiffness) were measured on postinoculation days (PIDs) 0 to 28 in rats. Acute analgesic efficacies of drugs were evaluated on PID 9 when degrees of allodynia, hyperalgesia, and joint stiffness in the ipsilateral paw reached almost the maximum, although those in the contralateral paw changed only slightly. In the ipsilateral paw, thermal hyperalgesia reached the maximum on PID 1, whereas mechanical allodynia and joint hyperalgesia progressively developed during the first 7 or 8 days, being tuned in to arthritis development. In the contralateral paw, thermal hyperalgesia never occurred, whereas mechanical allodynia and joint hyperalgesia developed after PID 11. Morphine and tramadol had full efficacies for all the pain parameters tested at sedation-inducing doses. Indomethacin and diclofenac significantly but partially improved thermal and joint hyperalgesia. Amitriptyline significantly reduced thermal and joint hyperalgesia only at sedation-inducing dose. Acetaminophen, carbamazepine, and gabapentin had, at the most, very small efficacies. In conclusion, the present study provided integrated information about the time course of pain and other disease development parameters in the CFA-induced arthritic rats, and clarified acute efficacies of different categories of analgesics for the allodynia and hyperalgesia.     

Successful treatment of hypovascular advanced hepatocellular carcinoma with lipiodol-targetting intervention radiology

We report a case of hypovascular advanced hepa-tocellular carcinoma (HCC) successfully treated with a novel combination therapy of percutaneous ethanol-lipiodol injection (PELI) and intervention radiology (IVR),lipiodol-targetting IVR (Lipi-IVR). The present case had a hypovascular HCC (3 cm in diameter) located in the S6 region of the liver. Although the tumor was not detectable at all by both of early and late phase of helical dynamic computed tomography (CT),it could be detected by ultrasonography (US) as a low echoic space occupying lesion (SOL) beside the gallbladder and right kidney. Serum levels of alpha fetoprotein (AFP) and AFP-L3 were extremely high. Combination therapy of PELI,firstly reported in our department,and IVR (PELI and IVR,lipiodol-targetting IVR) was performed twice for the treatment. PELI could effectively visualize the location of the tumor for IVR treatment and show the presence of a thin blood vessel branching from the right hepatic artery flowing into the lipiodol deposit. After treatment,the serum levels of AFP and AFP-L3 were rapidly decreased to normal and maintained for more than eight months. Thus,this case expressing the tremendous effect might give us insight into the effectiveness of the novel combination therapy of PELI and IVR for the treatment of hypovascular HCC.