One Minute of EEG Data Provides Sufficient and Reliable Data for Identifying Lewy Body Dementia.

OBJECTIVE: To determine the minimum duration of electroencephalography (EEG) data necessary to differentiate EEG features of Lewy body dementia (LBD), that is, dementia with Lewy bodies and Parkinson disease dementia, from non-LBD patients, that is, Alzheimer disease and Parkinson disease. METHODS: We performed quantitative EEG analysis for 16 LBD and 14 non-LBD patients. After artifact removal, a fast Fourier transform was performed on 90, 60, and thirty 2-second epochs to derive dominant frequency; dominant frequency variability; and dominant frequency prevalence. RESULTS: In LBD patients, there were no significant differences in EEG features derived from 90, 60, and thirty 2-second epochs (all P >0.05). There were no significant differences in EEG features derived from 3 different groups of thirty 2-second epochs (all P >0.05). When analyzing EEG features derived from ninety 2-second epochs, we found that LBD had significantly reduced dominant frequency, reduced dominant frequency variability, and reduced dominant frequency prevalence alpha compared with the non-LBD group (all P <0.05). These same differences were observed between the LBD and non-LBD groups when analyzing thirty 2-second epochs. CONCLUSIONS: There were no differences in EEG features derived from 1 minute versus 3 minutes of EEG data, and both durations of EEG data equally differentiated LBD from non-LBD.

C-type lectin MCL is an FcRγ-coupled receptor that mediates the adjuvanticity of mycobacterial cord factor.

Cord factor, also called trehalose-6,6'-dimycolate (TDM), is a potent mycobacterial adjuvant. We herein report that the C-type lectin MCL (also called Clec4d) is a TDM receptor that is likely to arise from gene duplication of Mincle (also called Clec4e). Mincle is known to be an inducible receptor recognizing TDM, whereas MCL was constitutively expressed in myeloid cells. To examine the contribution of MCL in response to TDM adjuvant, we generated MCL-deficient mice. TDM promoted innate immune responses, such as granuloma formation, which was severely impaired in MCL-deficient mice. TDM-induced acquired immune responses, such as experimental autoimmune encephalomyelitis (EAE), was almost completely dependent on MCL, but not Mincle. Furthermore, by generating Clec4e(gfp) reporter mice, we found that MCL was also crucial for driving Mincle induction upon TDM stimulation. These results suggest that MCL is an FcRγ-coupled activating receptor that mediates the adjuvanticity of TDM.

Silicone allergy associated with intraocular silicone ball prosthesis in a dog.

A 13-year-old, male Pomeranian dog was presented for scleral rupture with intraocular hemorrhage and retinal detachment in the right eye. After intrascleral silicone ball prosthesis, recurrent swelling and granulomatous blepharitis were observed for 140 d and finally melting keratitis developed. Although an intraorbital prosthesis was implanted, recurrent, serious, erosive, and ulcerative blepharitis developed with high plasma C-reactive protein concentrations. Since the blepharitis could not be controlled, the silicone ball was removed and the affected orbit was debrided. The blepharitis resolved rapidly, and the orbit healed routinely. Positive allergic reactions to silicone were discovered through a patch test. Key clinical message: To the authors' knowledge, this is the first report on silicone allergy in a dog with positive allergic reactions to silicone in the patch test.

Allergie au silicone associée à une prothèse intraoculaire en boule de silicone chez un chien. Un chien poméranien mâle de 13 ans a été présenté pour rupture sclérale avec hémorragie intraoculaire et décollement de la rétine de l'oeil droit. Après l'implantation intrasclérale d'une boule de silicone comme prothèse, un gonflement récurrent et une blépharite granulomateuse ont été observés pendant 140 jours et une kératite fondante s'est finalement développée. Bien qu'une prothèse intra-orbitaire ait été implantée, une blépharite récurrente, grave, érosive et ulcéreuse s'est développée, avec des concentrations plasmatiques élevées de protéine C réactive. Comme la blépharite ne pouvait pas être contrôlée, la boule de silicone a été retirée et l'orbite affectée a été débridée. La blépharite s'est résolue rapidement et l'orbite a guéri normalement. Des réactions allergiques positives au silicone ont été découvertes grâce à un test cutané.Message clinique clé :À la connaissance des auteurs, il s'agit du premier rapport sur une allergie au silicone chez un chien ayant des réactions allergiques positives au silicone lors du test cutané.(Traduit par Dr Serge Messier).

The Relationship between Functional Outcome and Prehospital Time Interval in Patients with Cerebral Infarction.

BACKGROUND: When symptoms of cerebral infarction are recognized in a patient, he or she should be transported to a hospital and should be started on the appropriate treatments. The effectiveness of delayed treatment of cerebral infarction with respect to the initial diagnosis or perception of the disease is still unclear. METHODS: We retrospectively investigated whether the functional outcomes would improve if patients with cerebral infarction were transported to the hospital with minimum delay. One-hundred twenty-two patients who were transported to Mishuku Hospital from January 2012 to August 2015 were included. We conducted multiple regression analyses. The criterion variable included the BI at discharge, and the explanatory variables were age, sex, days of hospital stay, the Barthel Index (BI) on admission, time from symptom onset to hospital arrival, time from emergency medical service perception to hospital arrival, recombinant tissue plasminogen activator (rt-PA) treatment, and the occluded artery type. RESULTS: In all 122 cases, the BI at the time of discharge was not related to onset time (P = .453) but was significantly related to perception time (P = .026). BI scores at discharge were high for young patients (P = .002) and for patients with short hospital stays (P <.001). In the rt-PA group (52 cases), BI scores at discharge were also high when the perception time was short (P = .036). CONCLUSIONS: A short interval between perception and hospital arrival improves the functional outcomes for patients with cerebral infarction. Thus, patients with cerebral infarctions must be treated with minimal delay after diagnosis of the condition.

[Association of Lower limb Neuropathy with Lumboperitoneal Shunt Transection:A Case Report].

A 49-year-old woman suffered hydrocephalus after subarachnoid hemorrhage, and underwent a lumboperitoneal(LP)shunt operation. X-ray imaging revealed that a spinal catheter inserted into the cranial side from L2/3 turned caudally at the Th12 level. Postoperative numbness and pain of the left buttocks and posterior femoral region persisted. The spinal catheter was pulled about 5 cm to improve flexure, and was reconnected 10 months after the shunt procedure. Symptoms improved, but a similar symptom developed one and a half years later. The spinal catheter was torn at the connection to the shunt valve. The catheter curved to the left side of the spinal cord and the catheter tip was located around the right Th12/L1 intervertebral foramen. We continued observations with analgesics, but symptoms did not subside. The shunt was removed 16 months after symptom relapse, and symptoms disappeared immediately. Bent insertion of the lumbar catheter is a potential cause of lower limb neuropathy after LP shunt operation. Attention must also be paid to the continuity of the catheter in follow-up after shunt procedures.

Recombinant production and characterization of human anti-influenza virus monoclonal antibodies identified from hybridomas fused with human lymphocytes.

In previous studies, hybridomas producing human immunoglobulin G, the antibodies 5E4 and 5A7 against influenza A and B virus were established using a novel human lymphocyte fusion partner, SPYMEG. In the present study, we succeeded in achieving the recombinant production and secretion of 5E4 and 5A7 in Chinese hamster ovary cells. Our N-glycan analysis by intact-mass detection and liquid chromatography mass spectrometry showed that recombinant 5E4 and 5A7 have one N-glycan and the typical mammalian-type N-glycan structures similar to those in hybridomas. However, the glycan distribution was slightly different among these antibodies. The amount of high-mannose-type structures was under 10% of the total N-glycans of recombinant 5E4 and 5A7, compared to 20% of the 5E4 and 5A7 produced in hybridomas. The amount of galactosylated N-glycans was increased in recombinants. Approximately 80% of the N-glycans of all antibodies was fucosylated, and no sialylated N-glycan was found. Recombinant 5E4 and 5A7 neutralized pandemic influenza A virus specifically, and influenza B virus broadly, quite similar to the 5E4 and 5A7 produced in hybridomas, respectively. Here we demonstrated that recombinants of antibodies identified from hybridomas fused with SPYMEG have normal N-glycans and that their neutralizing activities bear comparison with those of the original antibodies.

Landscape of protein-protein interactions in Drosophila immune deficiency signaling during bacterial challenge.

The Drosophila defense against pathogens largely relies on the activation of two signaling pathways: immune deficiency (IMD) and Toll. The IMD pathway is triggered mainly by Gram-negative bacteria, whereas the Toll pathway responds predominantly to Gram-positive bacteria and fungi. The activation of these pathways leads to the rapid induction of numerous NF-κB-induced immune response genes, including antimicrobial peptide genes. The IMD pathway shows significant similarities with the TNF receptor pathway. Recent evidence indicates that the IMD pathway is also activated in response to various noninfectious stimuli (i.e., inflammatory-like reactions). To gain a better understanding of the molecular machinery underlying the pleiotropic functions of this pathway, we first performed a comprehensive proteomics analysis to identify the proteins interacting with the 11 canonical members of the pathway initially identified by genetic studies. We identified 369 interacting proteins (corresponding to 291 genes) in heat-killed Escherichia coli-stimulated Drosophila S2 cells, 92% of which have human orthologs. A comparative analysis of gene ontology from fly or human gene annotation databases points to four significant common categories: (i) the NuA4, nucleosome acetyltransferase of H4, histone acetyltransferase complex, (ii) the switching defective/sucrose nonfermenting-type chromatin remodeling complex, (iii) transcription coactivator activity, and (iv) translation factor activity. Here we demonstrate that sumoylation of the IκB kinase homolog immune response-deficient 5 plays an important role in the induction of antimicrobial peptide genes through a highly conserved sumoylation consensus site during bacterial challenge. Taken together, the proteomics data presented here provide a unique avenue for a comparative functional analysis of proteins involved in innate immune reactions in flies and mammals.

Molecular changes associated with the development of resistance to imatinib in an imatinib-sensitive canine neoplastic mast cell line carrying a KIT c.1523A>T mutation.

Although imatinib has therapeutic activity for certain subsets of patients with mastocytosis, it is not always curative. Here, molecular mechanisms that confer imatinib resistance to neoplastic mast cells were investigated using an imatinib-sensitive canine neoplastic mast cell line VI-MC carrying a KIT c.1523A>T activating mutation. Two imatinib-resistant sublines were established by culturing VI-MC cells in increasing concentrations of imatinib (1 µM resistant, rVI-MC1; 10 µM resistant, rVI-MC10). Both sublines had a second KIT mutation c.2443G>C. Recombinant KIT with the second mutation was insensitive to 1 µM but sensitive to 10 µM imatinib. The effect of imatinib on the phosphorylation of KIT and its downstream signalling proteins was then examined using these sublines. KIT and ERK were constitutively phosphorylated in both sublines, and their phosphorylation was suppressed by 10 µM imatinib in rVI-MC1 cells. However, KIT but not ERK phosphorylation was suppressed in rVI-MC10 cells. The phosphorylation of ERK in rVI-MC10 cells was also not diminished by the Src family kinase (SFK) inhibitor dasatinib. This second mutation in KIT may play an important role in imatinib resistance in neoplastic mast cells. Furthermore, KIT/SFK-independent activation of ERK would be involved in imatinib resistance when the neoplastic cells are exposed to higher concentrations of imatinib.

[Case Report of Cerebellar Vermis Arteriovenous Malformation Presenting with Hydrocephalus due to Aqueductal Stenosis].

A 56-year-old man complained of gait disturbance and confused thinking. Magnetic resonance imaging(MRI)revealed an arteriovenous malformation(AVM)of the cerebellar vermis(Spetzler-Martin grade IV)causing hydrocephalus. One dilated precentral cerebellar vein was compressing the aqueduct. After feeder embolization over 3 sessions using N-butyl cyanoacrylate(NBCA), the nidus was reduced to one-third in size. However, symptoms remained unimproved, and endoscopic third ventriculostomy(ETV)was performed. The third ventricle showed thinning of the floor, with a fenestration in part of the floor. Radiological findings and clinical symptoms improved, and the patient returned home after rehabilitation. The condition of the patient remained stable as of six months later. On angiography, the draining vein showed a pressure of 20 mmHg with no change in the residual AVM. Embolization alone achieved a reduction in nidus volume, but could not reduce venous pressure, and combination therapy including ETV proved necessary. Cases with hydrocephalus due to aqueductal stenosis by AVM are extremely rare. This pathology is discussed with reference to the literature.

Induction of anti-influenza immunity by modified green fluorescent protein (GFP) carrying hemagglutinin-derived epitope structure.

The development of vaccination methods that can overcome the emergence of new types of influenza strains caused by escape mutations is desirable to avoid future pandemics. Here, a novel type of immunogen was designed that targeted the conformation of a highly conserved region of influenza A virus hemagglutinin (HA) composed of two separate sequences that associate to form an anti-parallel ß-sheet structure. Our previous study identified this ß-sheet region as the structural core in the epitope of a characteristic antibody (B-1) that strongly neutralizes a wide variety of strains within the H3N2 serotype, and therefore this ß-sheet region was considered a good target to induce broadly reactive immunity against the influenza A virus. To design the immunogen, residues derived from the B-1 epitope were introduced directly onto a part of enhanced green fluorescent protein (EGFP), whose surface is mostly composed of ß-sheets. Through site-directed mutagenesis, several modified EGFPs with an epitope-mimicking structure embedded in their surface were prepared. Two EGFP variants, differing from wild-type (parental) EGFP by only five and nine residues, induced mice to produce antibodies that specifically bind to H3-type HA and neutralize H3N2 virus. Moreover, three of five mice immunized with each of these EGFP variants followed by a booster with equivalent mCherry variants acquired anti-viral immunity against challenge with H3N2 virus at a lethal dosage. In contrast to conventional methods, such as split HA vaccine, preparation of this type of immunogen requires less time and is therefore expected to be quickly responsive to newly emerged influenza viral strains.

Human monoclonal antibodies derived from a patient infected with 2009 pandemic influenza A virus broadly cross-neutralize group 1 influenza viruses.

Influenza viruses are a continuous threat to human public health because of their ability to evolve rapidly through genetic drift and reassortment. Three human monoclonal antibodies (HuMAbs) were generated in this study, 1H11, 2H5 and 5G2, and they cross-neutralize a diverse range of group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H5N1 and H9N2. The three HuMAbs were prepared by fusing peripheral blood lymphocytes from an H1N1pdm-infected patient with a newly developed fusion partner cell line, SPYMEG. All the HuMAbs had little hemagglutination inhibition activity but had strong membrane-fusion inhibition activity against influenza viruses. A protease digestion assay showed the HuMAbs targeted commonly a short α-helix region in the stalk of the hemagglutinin. Furthermore, Ile45Phe and Glu47Gly double substitutions in the α-helix region made the HA unrecognizable by the HuMAbs. These two amino acid residues are highly conserved in the HAs of H1N1, H5N1 and H9N2 viruses. The HuMAbs reported here may be potential candidates for the development of therapeutic antibodies against group 1 influenza viruses.

A human monoclonal antibody derived from a vaccinated volunteer recognizes heterosubtypically a novel epitope on the hemagglutinin globular head of H1 and H9 influenza A viruses.

Most neutralizing antibodies elicited during influenza virus infection or by vaccination have a narrow spectrum because they usually target variable epitopes in the globular head region of hemagglutinin (HA). In this study, we describe a human monoclonal antibody (HuMAb), 5D7, that was prepared from the peripheral blood lymphocytes of a vaccinated volunteer using the fusion method. The HuMAb heterosubtypically neutralizes group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H9N2, with a strong hemagglutinin inhibition activity. Selection of an escape mutant showed that the HuMAb targets a novel conformational epitope that is located in the HA head region but is distinct from the receptor binding site. Furthermore, Phe114Ile substitution in the epitope made the HA unrecognizable by the HuMAb. Amino acid residues in the predicted epitope region are also highly conserved in the HAs of H1N1 and H9N2. The HuMAb reported here may be a potential candidate for the development of therapeutic/prophylactic antibodies against H1 and H9 influenza viruses.

Carotid Artery Stenting via Radial Access with Modified Flow Reversal Method: Case Series.

OBJECTIVE: Neuroendovascular treatment via transradial access (TRA) has gained popularity as a minimally invasive technique. However, the flow reversal (FR) system, reported useful in carotid artery stenting (CAS), cannot be applied via TRA because it requires an access route of more than 8 F. Herein, we report the utility of a modified FR system applied via TRA using a sheathless 8-F balloon guide catheter and a 2.6-F balloon catheter. METHODS: In a retrospective analysis of a single-center consecutive case series, patients with CAS and vulnerable plaques who were treated with CAS via TRA using a modified FR system from June 2022 to August 2022 were examined. High-intensity spots were assessed on postprocedural diffusion-weighted magnetic resonance images. Puncture site complications at discharge and cardiovascular events for 1 year after CAS were also evaluated. RESULTS: Ten patients were included in this study. There were no high-intensity spots on diffusion-weighted magnetic resonance images after CAS. No procedure-related complications, including radial artery occlusion or cardiovascular events, were observed. CONCLUSIONS: This study suggests that CAS with FR using our modified system is feasible via TRA and may be an effective technique with a low rate of vascular complications.

Prognostic value of tumour-related factors associated with canine retroperitoneal hemangiosarcoma in comparison with other anatomic presentations: A retrospective observational study.

BACKGROUND: Dogs with retroperitoneal hemangiosarcoma (HSA) exhibit variable postoperative median survival times (MST). OBJECTIVE: To retrospectively evaluate the prognostic value of selected tumour-related factors, such as tumour size, rupture, invasion into adjacent tissue, involvement of lymph node and distant metastasis, they were analysed in dogs with retroperitoneal HSA. METHODS: Ten dogs with retroperitoneal HSA managed solely with surgical excision were reviewed and compared with spleen (71) and liver (9) HSA. The Kaplan-Meier method and log-rank analysis were used compare MSTs between factors. Multivariable Cox proportional-hazard analysis was used to compare differences between arising sites. RESULTS: Retroperitoneal HSA showed comparatively longer postoperative MST compared with that of spleen and liver HSA and demonstrated significantly longer MST (p = 0.003) for tumours ≥5 cm (195 days) than <5 cm (70 days). Spleen HSA revealed significantly shorter MSTs in involvement of distant lymph nodes (23 days) and distant metastasis (39 days) than those in negative (83 days, p = 0.002 and 110 days, p < 0.001, respectively). Liver HSA also revealed significantly shorter MST (16.5 days compared with 98 days, p = 0.003) for distant metastasis. Additionally, hazard ratios (HRs) and their forest plot for overall HSA revealed as poor prognostic factors, arising sites (spleen; HR 2.78, p = 0.016 and liver; HR 3.62, p = 0.019), involvement of distant lymph nodes (HR 2.43, p = 0.014), and distant metastasis (HR 2.86, p < 0.001), and as better prognostic factor of tumour size ≥5 cm (HR 0.53, p = 0.037). CONCLUSION: In combination with overall HSA, retroperitoneal HSA shows comparatively longer postoperative MST compared to spleen and liver HSA, associated with tumour size ≥5 cm suggesting better prognostic factor.

Variables influencing anti-human immunodeficiency virus type 1 neutralizing human monoclonal antibody (NhMAb) production among infected Thais.

We conducted this study to determine the clinical variables associated with the production of human immunodeficiency virus type 1 (HIV-1) circulating recombinant form (CRF) 01_AE neutralizing human monoclonal antibodies (NhMAbs) using a hybridoma technique. This cross sectional study was performed in 20 asymptomatic HIV-1-infected Thais. Peripheral blood mononuclear cells (PBMCs) were obtained from each study participant and fused with SPYMEG cells. Culture supernatant collected from growing hybridomas was tested for neutralizing activity against HIV-1 CRF01_AE Env-recombinant viruses. Fifty hybridomas expressing anti-HIV-1 NhMAbs with strong neutralizing activity against at least 1 CRF01_AE Env-recombinant virus were found. A positive association between the numbers of hybridomas produced and the CD4 counts of study participants (p = 0.019) was observed. NhMAb-producing hybridomas with strong neutralizing activity were mostly found in participans diagnosed with HIV-1 infection within the previous 1 year. The HIV-1 viral load was not significantly correlated with the numbers of either established hybridomas or clones expressing anti-HIV-1 NhMAbs with strong neutralizing activity. To our knowledge, this is the first study of NhMAb-producing hybridomas obtained from HIV-1 CRF01_AE-infected populations identified by antibody binding to HIV-1 V3 loop peptide enzyme-linked immunosorbent assay (ELISA) or TRUGENE HIV-1 Genotyping Assay (HIV-1 pol sequence). It provides important criterion to slect study participants with high CD4 counts who produce large numbers of hybridoma clones. The results are valuable for further studies related to nurtalizing antibodies production and HIV-1 vaccine development.

The Short-Term Outcome of Middle Meningeal Artery Embolization for Chronic Subdural Hematoma with Mild Symptom: Case Series.

OBJECTIVE: A few reports have demonstrated the efficacy of middle meningeal artery embolization (MMAE) alone for mildly symptomatic chronic subdural hematoma (CSDH); however, the clinical course in the early posttreatment period remains unclear. The purpose of this study was to analyze the short-term outcomes of this technique at our center. METHODS: This study was based on a retrospective analysis of a single-center consecutive case series. Patients with mildly symptomatic CSDH treated with MMAE alone between July 2020 and June 2022 were examined. Neurological examinations and head computed tomography scans were performed before treatment and 1, 7, 14, and 28 days after treatment. The clinical course of the patients was analyzed. In particular, symptom improvement within 1 week from treatment or rescue evacuation and the factors associated were evaluated. RESULTS: Fifteen patients were included in this study. No procedure-related complications occurred. Partial or complete recovery within the first week from treatment was observed in 10 cases (66.7%), and the symptoms resolved completely in a median of 26 (6.5-33.5) days. Rescue evacuation was needed in 3 cases (20.0%). The hematoma volume and midline shift gradually decreased from baseline, with a significant improvement within the first week (P = 0.030 and 0.0032, respectively). CONCLUSIONS: MMAE alone provides relatively early improvement in cases of mildly symptomatic CSDH and may be a potential alternative to surgical evacuation or medical therapy.

Feasibility and Challenges of Transradial Approach in Neuroendovascular Therapy: A Retrospective Observational Study.

Objective: Transradial approach (TRA) is increasingly used as a viable alternative to the traditional transfemoral approach (TFA) in neuroendovascular therapy (NET) owing to its potential anatomical benefits and lower puncture-site complication rates. However, the real-world challenges of implementing TRA-NET have not been thoroughly studied, particularly those related to guide catheter (GC) placement. In this study, we aimed to explore the feasibility and challenges of TRA-NET, with a specific focus on GC placement. Methods: This retrospective observational study included patients who underwent NET at our institution between December 2019 and May 2022. Procedural success was defined as the successful placement of a GC in the target vessel. Cases in which a Simmons-shaped GC was used or the approach was changed to TFA were classified as difficult. Safety was assessed based on the rate of severe puncture-site complications requiring either blood transfusion or surgical intervention. Results: Among the 310 patients who underwent NET during the study period, 222 (71.6%) with a median age of 74 years were selected for TRA-NET. The target vessel was in the left anterior circulation (LtAC) in 101 (45.5%) patients, and 8-F GCs were the most frequently used (40.1%). TRA-NET achieved a 95.0% success rate, with a switch to TFA required in 5.0% of the cases. Procedural challenges occurred in 42 (18.9%) patients, primarily in those with LtAC lesions. Specifically, a type III aortic arch (p <0.0001) and age ≥80 years (p = 0.01) were significantly associated with procedural difficulties. Radial artery evaluation was confirmed in 66 cases (29.7%), revealing one instance (1.5%) of radial artery occlusion. No severe puncture-site complications were observed. Conclusion: TRA-NET may provide substantial therapeutic benefits without significant limitations in device use. However, it may be challenging, particularly in older patients and those with a type III aortic arch with LtAC lesions. Consequently, careful selection of the approach route is imperative.

Fentanyl sparing effect of ultrasound-guided proximal radial, ulnar, median, and musculocutaneous nerve (RUMM) block for radial and ulnar fracture repair in dogs: a retrospective case-control study.

This study retrospectively evaluated the fentanyl-sparing effect of ultrasound-guided proximal radial, ulnar, median, and musculocutaneous nerve (RUMM) block for radial and ulnar fracture repair in dogs. Fentanyl was prepared for intraoperative analgesia in dogs, although proximal RUMM block was performed using 0.5% or 0.25% bupivacaine before surgery in the block group. Dogs without a nerve block were assigned to the control group. The fentanyl dose in the block group [0.8 (0-1.9) µg/kg/hr] [median (interquartile range)] was significantly lower than in the control group [8.4 (7.2-10) µg/kg/hr]. Surgery was performed without fentanyl in >50% of the dogs (5/7), using 0.5% bupivacaine. Ultrasound-guided proximal RUMM block can be useful as an intraoperative analgesic for radial and ulnar fracture repair in dogs.

[Long-standing overt ventriculomegaly in adults (LOVA) needing ventriculo-peritoneal shunt with double programmable pressure valves].

A 44-year-old man presented with symptomatic hydrocephalus due to aqueductal stenosis. Endoscopic third ventriculostomy was performed but proved ineffective, so ventriculo-peritoneal shunt using a programmable pressure valve (PPV) was carried out. Subdural hematoma appeared 5 weeks postoperatively and subsequently increased though the pressure setting was maximum. One more valve was implanted in the right chest wall and drainage of the hematoma was performed 2 months after the shunt operation. Adjustment of pressure was repeated. Findings of overdrainage and underdrainage were seen once each afterwards. We followed up the patient with the first valve set at 200 mm H2O and the second valve set at 60 mm H2O. Disturbance of memorization improved. The patient was in a stable condition 10 months after the final pressure settings. Flow volume changes were examined under conditions of various pressures in tandemly connected double programmable valves in vitro. When total pressure increased, flow showed a linear decrease that was not associated with the order of the pressure settings. This method of adding one more PPV was effective, and appears to be a useful choice for treating overdrainage.

Coincidence of v-raf murine sarcoma viral oncogene homolog B mutation (V595E) with phosphorylated v-raf murine sarcoma viral oncogene homolog B in urothelial carcinoma in dogs.

Expression of phosphorylated v-raf murine sarcoma viral oncogene homolog B (pBRAF) and phosphorylated extracellular signal-regulated kinase1/2 (pERK1/2) were investigated in urothelial carcinoma (UC) in dogs with or without the BRAF gene mutation (V595E). Among the 10 cases of UC with V595E (-), cytoplasmic immunoreactivity against pBRAF of neoplastic cells was reported in 8, with 7 displaying moderate reactivity and 1 displaying intense reactivity. Nuclear immunoreactivity against pBRAF was detected in 5 cases; however, these reactivities were non-specific, due to pBRAF being limited in the cytoplasm. In addition, positive cytoplasmic immunoreactivity against pERK1/2 of neoplastic cells was detected in 7 cases and nuclear immunoreactivity against ERK1/2 was detected in 6 cases. Among the 13 cases of UC with V595E (+), cytoplasmic immunoreactivity against pBRAF of neoplastic cells was detected in all 13 cases and nuclear immunoreactivity against pBRAF was detected in 10 cases; however, the nuclear immunoreactivity was non-specific. Cytoplasmic immunoreactivity against pERK1/2 of neoplastic cells was detected in all 13 cases and nuclear immunoreactivity against pERK1/2 was also detected in all cases. As nuclear pERK1/2 indicates a progressive signaling process in the mitogen-activated protein kinase pathway, V595E (+) UC might be in its growing stage. Probable phosphorylated sites of pBRAF at Thr598/Ser601, detected in this study, are major and essential sites of the upstream rat sarcoma viral oncogene homolog (RAS) signaling pathway. In human cancers, the BRAF mutation never coincides with oncogenic RAS. To our knowledge, this is the first report on the simultaneous occurrence of the BRAF mutation (V595E) and pBRAF expression (at Thr598/Ser601) in dogs with UC with V595E (+).

L'expression de l'homologue B de l'oncogène viral du sarcome murin phosphorylé v raf (pBRAF) et de la kinase1/2 régulée par le signal extracellulaire phosphorylé (pERK1/2) ont été étudiées dans le carcinome urothélial (CU) chez des chiens avec ou sans la mutation du gène BRAF (V595E). Parmi les 10 cas de CU avec V595E (−), une immunoréactivité cytoplasmique contre pBRAF de cellules néoplasiques a été rapportée chez huit, sept présentant une réactivité modérée et un présentant une réactivité intense. L'immunoréactivité nucléaire contre pBRAF a été détectée dans cinq cas; cependant, ces réactivités n'étaient pas spécifiques, car pBRAF était limité dans le cytoplasme. De plus, une immunoréactivité cytoplasmique positive contre pERK1/2 des cellules néoplasiques a été détectée dans sept cas et une immunoréactivité nucléaire contre ERK1/2 a été détectée dans six cas. Parmi les 13 cas de CU avec V595E (+), une immunoréactivité cytoplasmique contre pBRAF de cellules néoplasiques a été détectée dans les 13 cas et une immunoréactivité nucléaire contre pBRAF a été détectée dans 10 cas; cependant, l'immunoréactivité nucléaire était non spécifique. L'immunoréactivité cytoplasmique contre pERK1/2 des cellules néoplasiques a été détectée dans les 13 cas et l'immunoréactivité nucléaire contre pERK1/2 a également été détectée dans tous les cas. Comme le pERK1/2 nucléaire indique un processus de signalisation progressif dans la voie de la protéine kinase activée par les mitogènes, V595E (+) UC pourrait être dans sa phase de croissance. Les sites phosphorylés probables de pBRAF à Thr598/Ser601, détectés dans cette étude, sont des sites majeurs et essentiels de la voie de signalisation de l'oncogène viral (RAS) du sarcome de rat en amont. Dans les cancers humains, la mutation BRAF ne coïncide jamais avec le RAS oncogène. À notre connaissance, il s'agit du premier rapport sur la survenue simultanée de la mutation BRAF (V595E) et de l'expression de pBRAF (à Thr598/Ser601) chez des chiens atteints de CU avec V595E (+).(Traduit par Docteur Serge Messier).