Conscious sedation with midazolam intravenously for a patient with Parkinson's disease and unpredictable chorea-like dyskinesia.

Oral surgery can be difficult in patients with chorea-like dyskinesia, which is common in those on long-term levodopa medication for Parkinson's disease, and we know of no conclusive evidence to indicate whether conscious sedation with midazolam is effective in such cases. We report a patient in whom levodopa-induced chorea-like dyskinesia disappeared when midazolam was given intravenously for conscious sedation.

The vinylogous Catellani reaction: a combined computational and experimental study.

In the presence of 5 mol% Pd(OAc)2, 1 equiv. of norbornene, and K2CO3, the reaction of 4-iodo-2-quinolones with tertiary o-bromobenzylic alcohols produced the desired benzopyran-fused 2-quinolones in moderate to high yields. A Catellani-type mechanism involving vinylic C-H cleavage is proposed based on the results of control experiments and density functional theory calculations.

Charged particle flows in the beam extraction region of a negative ion source for NBI.

Experiments by a four-pin probe and photodetachment technique were carried out to investigate the charged particle flows in the beam extraction region of a negative hydrogen ion source for neutral beam injector. Electron and positive ion flows were obtained from the polar distribution of the probe saturation current. Negative hydrogen ion flow velocity and temperature were obtained by comparing the recovery times of the photodetachment signals at opposite probe tips. Electron and positive ions flows are dominated by crossed field drift and ambipolar diffusion. Negative hydrogen ion temperature is evaluated to be 0.12 eV.

CF3-Substituted semisquarate: a pluripotent building block for the divergent synthesis of trifluoromethylated functional molecules.

The first synthesis of a CF3-substituted semisquarate was accomplished via nucleophilic trifluoromethylation using CF3SiMe3 and subsequent rhenium-catalyzed allylic alcohol rearrangement. The short-step skeletal-divergent synthesis of trifluoromethylated functional molecules was successfully achieved using the CF3-substituted semisquarate as the platform.

A lactone-fused cyclohexadiene as a versatile platform for diversified synthesis of 5,6,5-tricyclic scaffolds.

A lactone-fused cyclohexadiene, which can be readily prepared by ruthenium(III)-catalyzed [2 + 2 + 2] cyclization of an enediyne, functioned as a versatile platform for the stereoselective synthesis of differently functionalized 5,6,5-tricyclic scaffolds.

BMP4/Thrombospondin-1 loop paracrinically inhibits tumor angiogenesis and suppresses the growth of solid tumors.

Bone morphogenetic protein 4 (BMP4) has potential as an anticancer agent. Recent studies have suggested that BMP4 inhibits the survival of cancer stem cells (CSCs) of neural and colon cancers. Here, we showed that BMP4 paracrinically inhibited tumor angiogenesis via the induction of Thrombospondin-1 (TSP1), and consequently suppressed tumor growth in vivo. Although HeLa (human cervical cancer), HCI-H460-LNM35 (highly metastatic human lung cancer) and B16 (murine melanoma) cells did not respond to the BMP4 treatment in vitro, the growth of xeno- and allografts of these cells was suppressed via reductions in tumor angiogenesis after intraperitoneal treatment with BMP4. When we assessed the mRNA expression of major angiogenesis-related factors in grafted tumors, we found that the expression of TSP1 was significantly upregulated by BMP4 administration. We then confirmed that BMP4 was less effective in suppressing the tumor growth of TSP1-knockdown cancer cells. Furthermore, we found that BMP4 reduced vascular endothelial growth factor (VEGF) expression in vivo in a TSP1-dependent manner, which indicates that BMP4 interfered with the stabilization of tumor angiogenesis. In conclusion, the BMP4/TSP1 loop paracrinically suppressed tumor angiogenesis in the tumor microenvironment, which subsequently reduced the growth of tumors. BMP4 may become an antitumor agent and open a new field of antiangiogenic therapy.

ErbB inhibitors ameliorate behavioral impairments of an animal model for schizophrenia: implication of their dopamine-modulatory actions.

Ligands for ErbB receptors, including epidermal growth factor (EGF) and neuregulin-1, have a neurotrophic activity on midbrain dopaminergic neurons and are implicated in the pathophysiology of schizophrenia. Although ErbB kinase inhibitors ameliorate behavioral deficits of the schizophrenia model that was established by hippocampal lesioning of rat pups, the antipsychotic action of ErbB kinase inhibitors and its general applicability to other models are not fully characterized. Using a different animal model, here, we examined whether and how ErbB kinase inhibitors ameliorate the behavioral endophenotypes relevant to schizophrenia. The animal model for schizophrenia was prepared by exposing neonatal rats to the cytokine EGF. Intraventricular infusion of the ErbB1 inhibitors ZD1839 and PD153035 in these animals ameliorated the deficits in startle response and prepulse inhibition in a dose-dependent manner. The deficits of latent inhibition of fear learning were also alleviated by ZD1839 with its limited effects on body weight gain or locomotor activity. ZD1839 infusion also decreased the busting activity of nigral dopamine (DA) neurons and reduced pallidal DA metabolism, a result that mimics the anti-dopaminergic profile of risperidone and haloperidol in this brain region. ErbB inhibitors appear to have anti-dopaminergic actions to alleviate some of the behavioral deficits common to animal models for schizophrenia.

Therapeutic potential of VEGF and VEGF-derived peptide in peripheral neuropathies.

Besides its prominent role in angiogenesis, the vascular endothelial growth factor (VEGF) also exerts important protective effects on neurons. In particular, mice expressing reduced levels of VEGF suffer from late-onset motor neuron degeneration, whereas VEGF delivery significantly delays motor neuron death in ALS mouse models, at least partly through neuroprotective effects. Additionally, VEGF protects dorsal root ganglion (DRG) neurons against paclitaxel-induced neurotoxicity. Here, we demonstrate that VEGF also protects DRG neurons against hyperglycemia-induced neuronal stress as a model of diabetes-induced peripheral neuropathy. Specifically, VEGF decreased expression of the stress-related gene activating transcription factor 3 (ATF3) in DRG neurons isolated from streptozotocin-induced diabetic mice (ex vivo) and in isolated DRG neurons exposed to high glucose concentrations (in vitro). In vivo, local VEGF application also protected against paclitaxel- and diabetes-induced neuropathies without causing side effects. A small synthetic VEGF mimicking pentadecapeptide (QK) exerted similar effects on DRG cultures: the peptide reduced ATF3 expression in vitro and ex vivo in paclitaxel- and hyperglycemia-induced models of neuropathy to a similar extent as the full-length recombinant VEGF protein. By using transgenic mice selectively overexpressing the VEGF receptor 2 in postnatal neurons, these neuroprotective effects were shown to be mediated through VEGF receptor 2. Overall, these results underscore the potential of VEGF and VEGF-derived peptides for the treatment of peripheral neuropathies.

Acute generalized exanthematous pustulosis during the puerperal period: a case report.

BACKGROUND: Acute generalized exanthematous pustulosis (AGEP) is an uncommon adverse cutaneous reaction, most commonly associated with drugs. CASE: A 38-year-old primigravida whose labor had been induced developed erythema over her chest and abdomen. She was transferred to our department after a failed vacuum extraction, and delivered a mature infant by forceps. On day three postpartum she developed a 40.4 degrees C fever. Although ceftriaxone was administered, her fever persisted (>38 degreesC). On day six of the puerperium, diffuse non-follicular pustules appeared over her neck and trunk, and AGEP was suspected. Two days after ceftriaxone was withdrawn, the eruptions started to resolve without any medical intervention. CONCLUSION: Once the diagnosis of AGEP has been made, the antibiotics being administered must be discontinued. If continued treatment is required, pharmacologically distinct antibiotics must be used instead to aid the rapid self-limitation of the disease.

Successful treatment of duodenal carcinoid tumor by laparoscopy-assisted endoscopic full-thickness resection with lymphadenectomy.

Reports on endoscopic full-thickness resection of the duodenum using the endoscopic submucosal dissection technique are rare. Here we present a case of a duodenal bulb carcinoid tumor successfully treated by laparoscopy-assisted endoscopic full-thickness resection (LAEFR). An asymptomatic 65-year-old woman had a 10-mm, submucosal tumor on the anterior wall of the duodenal bulb. Abdominal CT revealed an enlarged lymph node adjacent to the duodenum and pancreas. Although we informed the patient of the need for pancreatoduodenectomy with a lymphadenectomy, the patient expressly requested LAEFR. After negative nodal metastasis was confirmed by an intraoperative frozen section of the enlarged nodes, LAEFR was performed using the endoscopic submucosal dissection technique under the laparoscopic assistance. The duodenal wall defect was closed by laparoscopy with an Albert anastomosis. The entire circumferential margin of the specimen was histopathologically negative for carcinoid tumor cells. In summary, LAEFR enables en bloc and whole-layer excision of nonperiampullary duodenal lesions with a sufficient surgical margin, both vertically and laterally. LAEFR is a minimally invasive and effective treatment for selected patients with duodenal carcinoid tumor.

Electron density measurement of cesium seeded negative ion source by surface wave probe.

Electron density measurements of a large-scaled negative ion source were carried out with a surface wave probe. By comparison of the electron densities determined with the surface wave probe and a Langmuir probe, it was confirmed that the surface wave probe is highly available for diagnostic of the electron density in H(-) ion sources. In addition, it was found that the ratio of the electron density to the H(-) ion density dramatically decreases with increase of a bias voltage and the H(-) ions become dominant negative particles at the bias voltage of more than 6 V.

Spatial distribution of the charged particles and potentials during beam extraction in a negative-ion source.

We report on the characteristics of the electronegative plasma in a large-scale hydrogen negative ion (H(-)) source. The measurement has been made with a time-resolved Langmuir probe installed in the beam extraction region. The H(-) density is monitored with a cavity ring-down system to identify the electrons in the negative charges. The electron-saturation current decreases rapidly after starting to seed Cs, and ion-ion plasma is observed in the extraction region. The H(-) density steps down during the beam extraction and the electron density jumps up correspondingly. The time integral of the decreasing H(-) charge density agrees well with the electron charge collected with the probe. The agreement of the charges is interpreted to indicate that the H(-) density decreasing at the beam extraction is compensated by the electrons diffusing from the driver region. In the plasmas with very low electron density, the pre-sheath of the extraction field penetrates deeply inside the plasmas. That is because the shielding length in those plasmas is longer than that in the usual electron-ion plasmas, and furthermore the electrons are suppressed to diffuse to the extraction region due to the strong magnetic field.

An early MRI change following reversible hypoxic brain injury. A case report.

We describe a patient who suffered reversible hypoxic brain injury. The initial MRI taken 3.5 hours after asphyxiation showed an abnormal lesion on DWI, but he recovered completely from coma. The presence of cytotoxic edema in the acute stage may not necessarily indicate a poor prognosis.

Measurement and comparison of serum neuregulin 1 immunoreactivity in control subjects and patients with schizophrenia: an influence of its genetic polymorphism.

Neuregulin-1 (NRG1) gene is implicated in the etiology or neuropathology of schizophrenia, although its biological contribution to this illness is not fully understood. We have established an enzyme-linked immunosorbent assay (ELISA), which recognizes the NRG1beta1 immunoglobulin-like (Ig) domain, and measured soluble Ig-NRG1 immunoreactivity in the sera of chronic schizophrenia patients (n = 40) and healthy volunteers (n = 59). ELISA detected remarkably high concentrations of Ig-NRG1 immunoreactivity in human serum (mean 5.97 +/- 0.40 ng/mL, ~213 +/- 14 pM). Gender and diagnosis exhibited significant effects on serum Ig-NRG1 immunoreactivity. Mean Ig-NRG1 immunoreactivity in the schizophrenia group was 63.2% of that measured in the control group. Ig-NRG1 immunoreactivity in women was 147.1% of that seen in men. We also attempted to correlate six SNPs of NRG1 genome with serum Ig-NRG1 immunoreactivity. Analysis of covariance with compensation for gender identified a significant interaction between diagnosis and SNP8NRG243177 allele. The T allele of this SNP significantly contributed to the disease-associated decrease in Ig-NRG1 immunoreactivity. Although we hypothesized a chronic influence of antipsychotic medications, there was no significant effect of chronic haloperidol treatment on serum Ig-NRG1 immunoreactivity in monkeys. These findings suggest that serum NRG1 levels are decreased in patients with chronic schizophrenia and influenced by their SNP8NRG243177 alleles.

Characteristics of 80 keV positive ion source for Large Helical Device.

An additional beamline, BL5, equipped with four positive ion sources will be installed on Large Helical Device (LHD) in 2010. The performance of an ion source which generates 80 keV deuterium and 60 keV hydrogen beams was investigated. The structure of the ion source is based on that of a BL4 ion source on LHD. The main differences between the ion sources for the BL4 and BL5 are the acceleration voltages and the materials of plasma electrodes: copper and molybdenum, respectively. The molybdenum plasma electrode for BL5 has better performance than the copper plasma electrode of BL4. The integrated performance of the ion source for BL5 reached a value equivalent to approximately 58 A in the beam current of hydrogen positive ion at 60 keV in the beam energy.

Beamlet characteristics in the accelerator with multislot grounded grid.

Characteristics of multibeamlets are investigated by means of beamlet monitoring technique. The beamlets are extracted from an accelerator with multislot grounded grid and the profiles are observed as infrared images of temperature distributions on a cold isostatic pressed graphite plate exposed by H-beamlets. The optimal horizontal and vertical divergence angles of single beamlet are estimated at 4.1 and 6.1 mrad, respectively.

Stevens-Johnson syndrome and toxic epidermal necrolysis due to anticonvulsants share certain clinical and laboratory features with drug-induced hypersensitivity syndrome, despite differences in cutaneous presentations.

BACKGROUND: Drug-induced hypersensitivity syndrome (DIHS)/drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is characterized by late disease onset, fever, rash, hepatic dysfunction, haematological abnormalities, lymphadenopathy and often, human herpesvirus (HHV) reactivation. The diagnosis of DIHS is based on the combined presence of these findings. Anticonvulsants are a major cause of DIHS and may also cause Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We examined whether SJS/TEN due to anticonvulsants display similar clinical and laboratory features seen in DIHS. METHODS: Patients diagnosed with SJS or TEN due to anticonvulsants (n = 8) were examined and their clinical features and laboratory findings were compared with patients with anticonvulsant-related DIHS (n = 6). RESULTS: Seven of the eight patients with SJS/TEN developed symptoms > 3 weeks after starting anticonvulsants. Hepatic dysfunction was present in six patients with SJS/TEN and five patients with DIHS. Leucocytosis and/or eosinophilia was noted in seven patients with SJS/TEN and four patients with DIHS. Only one patient in the SJS/TEN group had atypical lymphocytosis; this was present in four patients with DIHS. Reactivation of HHV-6 was detected in one of the four patients tested in the SJS/TEN group, although it was seen in five of the six patients with DIHS. CONCLUSIONS: TSJS/TEN due to anticonvulsants may exhibit some clinical and laboratory features of DIHS. The nature of the cutaneous involvement should be emphasized in the diagnosis of DIHS.

A phase II study of palonosetron combined with dexamethasone to prevent nausea and vomiting induced by highly emetogenic chemotherapy.

BACKGROUND: This is a randomized, double-blind, dose-ranging study in patients receiving highly emetogenic chemotherapy (HEC) to evaluate the safety, efficacy, and pharmacokinetics of palonosetron, in combination with dexamethasone. MATERIALS AND METHODS: We randomized 233 patients to receive palonosetron as a single i.v. bolus dose of 0.075, 0.25, or 0.75 mg before administration of HEC. Dexamethasone (12-16 mg i.v. on day 1, 8 mg i.v. on day 2, and 4-8 mg i.v. on day 3) was administered for prophylactic antiemesis. Pharmacokinetics of palonosetron was analyzed in 24 patients. RESULTS: In this study, all patients were given > or =50 mg/m(2) cisplatin, which was considered to be HEC. No significant differences in complete response (CR: no emesis and no rescue medication) rates were found in the first 24 h between the 0.075-, 0.25-, and 0.75-mg groups (77.6%, 81.8%, and 79.5%, respectively). In the 120-h period of overall observation, CR rates increased in a dose-dependent manner. In the 0.75-mg group, we observed a significantly longer time to treatment failure than in the 0.075-mg group (median time >120 versus 82.0 h, P = 0.038). Palonosetron was tolerated well and did not show any dose-related increase in adverse effects. CONCLUSIONS: Palonosetron at doses of 0.25 and 0.75 mg was shown to be effective in preventing chemotherapy-induced nausea and vomiting with high CR rates of patients treated with HEC in Japan. All tested doses of palonosetron were tolerated well.