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In individuals with chronic neuropathic pain, the posterior insular cortex (PIC) has been found to exhibit increased glutamatergic activity, and the dysgranular portion of PIC (DPIC) has been investigated as a novel cortical target for pain modulation. However, the role of DPIC glutamatergic neurons (DPICg) in trigeminal neuropathic pain (TNP) remains unclear. Here, we examined the outcomes of DPICg inhibition in a rat model of chronic constriction injury of the infraorbital nerve (CCI-ION). Animals were randomly divided into TNP, sham, and control groups. TNP animals underwent CCI-ION surgery. Either optogenetic or null viruses were delivered to the contralateral DPICg of TNP and sham animals. In vivo single-unit extracellular recordings from the ipsilateral spinal trigeminal nucleus caudalis (TNC) and contralateral ventral posteromedial (VPM) thalamus were obtained under both "ON" and "OFF" stimulation states. Behavioral responses during the stimulation-OFF and stimulation-ON phases were examined. Expression of c-Fos, pERK, and CREB immunopositive neurons were also observed. Optogenetic inhibition of contralateral DPICg decreased the neural firing rate in both TNC and VPM thalamus, the expression of sensory-responsive cell bodies, and transcriptional factors in the DPIC of TNP group. Improvements in hyperalgesia, allodynia, and anxiety-like responses in TNP animals were also observed during stimulation-ON condition. In fine, descending pain processing is influenced by neuroanatomical projections from the DPIC to the pain matrix areas, and DPICg could play a necessary role in this neural circuitry. Therefore, the antinociceptive effect of DPICg inhibition in this study may provide evidence for the therapeutic potential of DPICg in TNP.
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Corteza Insular , Neuralgia , Ratas , Animales , Ratas Sprague-Dawley , Optogenética , Hiperalgesia/tratamiento farmacológico , Neuronas/metabolismoRESUMEN
This study investigates the long-term outcomes of clival chordoma patients treated with the endonasal transclival approach (ETCA) and early adjuvant radiation therapy. A retrospective review of 17 patients (2002-2013) showed a 10-year progression-free survival (PFS) rate of 67.4%, with the ETCA group showing fewer progressions and cranial neuropathies than those treated with combined approaches. The ETCA, a minimally invasive technique, provided a similar extent of resection compared to conventional skull-base approaches and enabled safe delivery of high-dose adjuvant radiotherapy. The findings suggest that ETCA is an effective treatment for centrally located clival chordomas.
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This study was conducted to establish the toxicological profile of combination treatment with therapeutic HPV DNA vaccines (GX-188E) and the long-acting form of recombinant human interleukin-7 fused with hybrid Fc (IL-7hyFc). GX-188E was administered intramuscularly by electroporation with or without IL-7hyFc intravaginally once per 2 weeks for 8 weeks (five times) in female Sprague-Dawley rats. Because up-regulation of immune responses and migration of antigen-specific T cells in cervicoviginal tissue were predicted as therapeutic effects, we distinguished adverse effects from therapeutic effects based on the severity of the systemic immune response, reversibility of lymphoid tissue changes, target tissue damage, and off-target immune responses. We observed that the number of neutrophils was increased, and the number of lymphocytes was decreased in the blood. Further, myofiber degeneration, necrosis, fibroplasia, and cell infiltration were observed at the GX-188E administration site. These changes were fully or partially recovered over a 4-week period. Analysis of lymphocytes in spleen revealed that CD4+ T cells and total T cells decreased in rats treated with GX-188E in combination with a high dose of IL-7hyFc (1.25 mg/animal). However, these changes were not considered adverse because they were transient and may have been related to electroporation-mediated DNA delivery or the local migration of lymphocytes induced by IL-7. Therefore, the potential toxicity of the combination of GX-188E and IL-7hyFc treatment was comparable to that of GX-188E treatment alone, and the no observed adverse effect level for GX-188E with IL-7hyFc was considered as 320 µg/animal for GX-188E and 1.25 mg/animal for IL-7hyFc.
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Fragmentos Fc de Inmunoglobulinas/toxicidad , Interleucina-7/toxicidad , Vacunas contra Papillomavirus/toxicidad , Vacunas de ADN/toxicidad , Administración Intravaginal , Animales , Biomarcadores/sangre , Biomarcadores/orina , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Electroporación , Femenino , Fragmentos Fc de Inmunoglobulinas/administración & dosificación , Interleucina-7/administración & dosificación , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Nivel sin Efectos Adversos Observados , Vacunas contra Papillomavirus/administración & dosificación , Ratas Sprague-Dawley , Proteínas Recombinantes de Fusión/toxicidad , Medición de Riesgo , Linfocitos T/efectos de los fármacos , Linfocitos T/metabolismo , Factores de Tiempo , Vacunas de ADN/administración & dosificaciónRESUMEN
PURPOSE: To determine the efficacy of the therapeutic DNA vaccine GX-188E for inducing regression of cervical intraepithelial neoplasia (CIN) 3. PATIENTS AND METHODS: We conducted a prospective, randomized, multicenter, open-label, phase II clinical trial of GX-188E in CIN3 patients positive for human papillomavirus (HPV) type 16/18. The primary endpoint was to determine the histopathologic regression to ≤CIN1 at visit seven (V7; 20 weeks after the first GX-188E injection), and an extension study was pursued until visit 8 (V8; 36 weeks after the first GX-188E injection). HPV-sequencing analysis and an ex vivo IFNγ ELISpot assay were performed using the collected cervical biopsy and blood samples from patients. RESULTS: In total, 72 patients were enrolled and underwent randomization. Of them, 64 patients were included in per-protocol analysis (V7) and 52 in extension analysis (V8). Our data showed 52% (33/64) of patients at V7 and 67% (35/52) of patients at V8 presented histopathologic regression after receiving the GX-188E injection. We found that 73% (V7) and 77% (V8) of the patients with histologic regression showed HPV clearance. HPV clearance and histopathologic regression were significantly associated at V7 and at V8. Compared with the measurements at V1 (baseline), the patients at V8 with HPV clearance showed significantly higher fold changes in their IFNγ ELISpot responses compared with those without HPV clearance. The HPV sequence analysis revealed that the HPV type 16 E6/E7 variants D25E, V83L, and N29S were inversely associated with histopathologic regression at V8. CONCLUSIONS: GX-188E is an effective therapeutic vaccine against a cohort containing only CIN3 patients.
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Infecciones por Papillomavirus/complicaciones , Vacunas contra Papillomavirus/uso terapéutico , Displasia del Cuello del Útero/tratamiento farmacológico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Vacunas de ADN/uso terapéutico , Adulto , Femenino , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/aislamiento & purificación , Papillomavirus Humano 18/genética , Papillomavirus Humano 18/aislamiento & purificación , Humanos , Infecciones por Papillomavirus/virología , Seguridad del Paciente , Estudios Prospectivos , Resultado del Tratamiento , Neoplasias del Cuello Uterino/inmunología , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virología , Displasia del Cuello del Útero/inmunología , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/virologíaRESUMEN
OBJECTIVE: Anterior cervical microforaminotomy (ACMF) is a motion-preserving surgical procedure. The purpose of this study is to assess radiologic changes of operated and adjacent segments after ACMF. METHODS: We retrospectively reviewed 52 patients who underwent ACMF between 1998 and 2008. From X-ray film-based changes, disc height and sagittal range of motion (ROM) of operated and adjacent segments were compared at preoperative and last follow-up periods. Radiological degeneration of both segments was analyzed as well. RESULTS: The mean follow-up period was 48.2 months. There were 78 operated, 52 upper adjacent, and 38 lower adjacent segments. There were statistically significant differences in the ROM and disc height of operated segment between preoperative and last follow-up periods. However, there were no statistically significant differences in the ROM and disc height of adjacent segment between both periods. Radiological degenerative changes of operated segments were observed in 30%. That of adjacent segments was observed in 11 and 11% at upper and lower segments, respectively. CONCLUSION: After mean 4-year follow-up periods, there were degenerative changes of operated segments. However, ACMF preserved motion and prevented degenerative changes of adjacent segments.
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UNLABELLED: Influenza A virus (IAV) infection frequently causes hospitalization and mortality due to severe immunopathology. Annual vaccination and antiviral drugs are the current countermeasures against IAV infection, but they have a limited efficacy against new IAV variants. Here, we show that intranasal pretreatment with Fc-fused interleukin-7 (IL-7-mFc) protects mice from lethal IAV infections. The protective activity of IL-7-mFc relies on transcytosis via neonatal Fc receptor (FcRn) in the lung and lasts for several weeks. Introduction of IL-7-mFc alters pulmonary immune environments, leading to recruitment of T cells from circulation and their subsequent residency as tissue-resident memory-like T (TRM-like) cells. IL-7-mFc-primed pulmonary TRM-like cells contribute to protection upon IAV infection by dual modes. First, TRM-like cells, although not antigen specific but polyclonal, attenuate viral replication at the early phase of IAV infection. Second, TRM-like cells augment expansion of IAV-specific cytotoxic T lymphocytes (CTLs), in particular at the late phase of infection, which directly control viruses. Thus, accelerated viral clearance facilitated by pulmonary T cells, which are either antigen specific or not, alleviates immunopathology in the lung and mortality from IAV infection. Depleting a subset of pulmonary T cells indicates that both CD4 and CD8 T cells contribute to protection from IAV, although IL-7-primed CD4 T cells have a more prominent role. Collectively, we propose intranasal IL-7-mFc pretreatment as an effective means for generating protective immunity against IAV infections, which could be applied to a potential prophylaxis for influenza pandemics in the future. IMPORTANCE: The major consequence of a highly pathogenic IAV infection is severe pulmonary inflammation, which can result in organ failure and death at worst. Although vaccines for seasonal IAVs are effective, frequent variation of surface viral proteins hampers development of protective immunity. In this study, we demonstrated that intranasal IL-7-mFc pretreatment protected immunologically naive mice from lethal IAV infections. Intranasal pretreatment with IL-7-mFc induced an infiltration of T cells in the lung, which reside as effector/memory T cells with lung-retentive markers. Those IL-7-primed pulmonary T cells contributed to development of protective immunity upon IAV infection, reducing pulmonary immunopathology while increasing IAV-specific cytotoxic T lymphocytes. Since a single treatment with IL-7-mFc was effective in the protection against multiple strains of IAV for an extended period of time, our findings suggest a possibility that IL-7-mFc treatment, as a potential prophylaxis, can be developed for controlling highly pathogenic IAV infections.
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Fragmentos Fc de Inmunoglobulinas/administración & dosificación , Factores Inmunológicos/administración & dosificación , Virus de la Influenza A/inmunología , Interleucina-7/administración & dosificación , Pulmón/inmunología , Infecciones por Orthomyxoviridae/prevención & control , Administración Intranasal , Animales , Femenino , Fragmentos Fc de Inmunoglobulinas/genética , Factores Inmunológicos/genética , Interleucina-7/genética , Depleción Linfocítica , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/genética , Linfocitos T/inmunologíaRESUMEN
Here, we demonstrate that electroporation-enhanced immunization with a rationally designed HPV DNA vaccine (GX-188E), preferentially targeting HPV antigens to dendritic cells, elicits a significant E6/E7-specific IFN-γ-producing T-cell response in all nine cervical intraepithelial neoplasia 3 (CIN3) patients. Importantly, eight out of nine patients exhibit an enhanced polyfunctional HPV-specific CD8 T-cell response as shown by an increase in cytolytic activity, proliferative capacity and secretion of effector molecules. Notably, seven out of nine patients display complete regression of their lesions and viral clearance within 36 weeks of follow up. GX-188E administration does not elicit serious vaccine-associated adverse events at all administered doses. These findings indicate that the magnitude of systemic polyfunctional CD8 T-cell response is the main contributing factor for histological, cytological and virological responses, providing valuable insights into the design of therapeutic vaccines for effectively treating persistent infections and cancers in humans.
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Infecciones por Papillomavirus/terapia , Vacunas contra Papillomavirus/uso terapéutico , Displasia del Cuello del Útero/terapia , Neoplasias del Cuello Uterino/terapia , Vacunas de ADN/uso terapéutico , Adulto , Formación de Anticuerpos , Linfocitos T CD8-positivos/inmunología , Femenino , Humanos , Inmunidad Celular , Persona de Mediana Edad , Proteínas Oncogénicas Virales/inmunología , Neoplasias del Cuello Uterino/virología , Adulto Joven , Displasia del Cuello del Útero/virologíaRESUMEN
OBJECTIVE: There are differences in the clinical characteristics and surgical results between upper (L1-2 and L2-3) and lower (L3-4, L4-5, and L5-S1) lumbar disc herniations. We conducted this study to compare the clinical features and surgical outcomes between the two types of lumbar disc herniations. METHODS: We retrospectively reviewed the clinical features of patients who underwent microdiscectomies from 2008 to 2012. We evaluated the clinical characteristics such as age, preoperative autonomic dysfunction, the presence or absence of previous lumbar surgery and fusion required during surgery. Visual Analogue Scale (VAS) scores about back pain and leg pain were evaluated preoperatively and at the final follow-up. RESULTS: Upper lumbar group (n=15) was significantly older than lower lumbar group (n=148). The incidence of autonomic dysfunction was significantly higher in upper lumbar group. The number of patients with a previous lumbar surgery was significantly greater in upper lumbar group. There was no statistical significance for fusion required during surgery between two groups. Both groups showed a significant decrease in the VAS scores of leg pain. VAS scores of back pain were significantly decreased in lower lumbar group. But this was not seen in upper lumbar group. Both groups showed significant improvement of Oswestry Disability Index score. CONCLUSION: Upper lumbar group had different clinical characteristics from those of lower lumbar group and these include older age, a higher incidence of autonomic dysfunctions and a higher incidence of patients with previous lumbar surgery. There were no significant differences in surgical outcomes, except for back pain, between two groups.
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OBJECTIVE: The purpose of this study is to analyze clinical characteristics and surgical outcomes of the far lateral and the paramedian disc herniations. METHODS: The 88 patients who underwent an operation for lumbar disc herniations were reviewed. Visual analogue scale of leg and back pain, occurrence of sensory dysesthesia and motor deficit before and after operations were used to compare the far lateral with the paramedian disc herniations. RESULTS: Statistically, the far lateral herniations had more severe radicular leg pain and showed more frequent occurrence of sensory dysesthesia than paramedian herniations before operation (p<0.05). In the far lateral herniation group, preoperatively, 15 patients (75%) had sensory dysesthesia and among them, 4 patients (27%) showed improvement. In the paramedian herniation group, preoperatively, 25 patients (37%) had sensory dysesthesia and among them, 21 patients (84%) showed improvement. The degree of improvement in sensory dysesthesia was statistically higher in paramedian herniation group (p<0.05). In the far lateral herniation group, preoperatively, 11 patients (55%) had motor deficit and among them, 10 patients (91%) showed improvement. In the paramedian herniations, preoperatively, 29 patients (43%) had motor deficit and among them, 25 patients (86%) showed improvement. The degree of improvement in motor deficit was not statistically significant between groups (p>0.05). CONCLUSION: Preoperatively, the far lateral herniations had more severe radicular leg pain and frequent occurrence of sensory dysesthesia. Postoperatively, the sensory dysesthesia was less improved and back pain was more severe in the far lateral herniations.
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Ankylosing spondylitis (AS) is a chronic systemic and inflammatory rheumatic disease with a variable course of the axial skeleton. Spinal involvement may accompany ossification of the ligaments, intervertebral disc, end-plates and apophyseal structures, and seems to be "bamboo spine". Because of these natures of the spine in AS, a spinal fracture can be occurred with minor trauma or spontaneously. The fracture of the AS can cause neurological complications extremely high, so special attention to prevent neurological deterioration. Operative management of the injured spine with AS is difficult, and associated with a high complication rate. Extreme care must be taken for surgery to prevent secondary neurological deterioration.
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The best treatment for clival chordoma is obtained with total surgical excision, sometimes combined with adjuvant radiotherapy. A cerebrospinal fluid (CSF) fistula is a fatal complication that may occur following extended transsphenoidal surgery (TSS) and adjuvant radiotherapy. We report a case of fulminant meningitis without a CSF fistula in a 57-year-old woman who underwent TSS and multiple radiotherapies for a clival chordoma. She presented to our emergency room with copious epistaxis and odor inside her nasal cavity and had an unexpected fatal outcome. She was diagnosed with meningitis based on CSF culture and blood culture. While treating clival chordomas with adjuvant radiotherapy, clinicians should be aware of the possibility of fulminant meningitis.
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OBJECTIVE: The purpose of the study is to determine the effectiveness and safety of nicardipine infusion for controlling blood pressure in patients with subarachnoid hemorrhage (SAH). METHODS: We prospectively evaluated 52 patients with SAH and treated with nicardipine infusion for blood pressure control in a 29 months period. The mean blood pressure of pre-injection, bolus injection and continuous injection period were compared. This study evaluated the effectiveness of nicardipine for each Fisher grade, for different dose of continuous nicardipine infusion, and for the subgroups of systolic blood pressure. RESULTS: The blood pressure measurement showed that the mean systolic blood pressure / diastolic blood pressure (SBP/DBP) in continuous injection period (120.9/63.0 mmHg) was significantly lower than pre-injection period (145.6/80.3 mmHg) and bolus injection period (134.2/71.3 mmHg), and these were statistically significant (p < 0.001). In each subgroups of Fisher grade and different dose, SBP/DBP also decreased after the use of nicardipine. These were statistically significant (p < 0.05), but there was no significant difference in effectiveness between subgroups (p > 0.05). Furthermore, controlling blood pressure was more effective when injecting higher dose of nicardipine in higher SBP group rather than injecting lower dose in lower SBP group, and it also was statistically significant (p < 0.05). During the infusion, hypotension and cardiogenic problems were transiently combined in five cases. However, patients recovered without any complications. CONCLUSION: Nicardipine is an effective and safe agent for controlling acutely elevated blood pressure after SAH. A more systemic study with larger patients population will provide significant results and will bring solid evidence on effectiveness of nicardipine in SAH.
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OBJECTIVE: A dural arteriovenous fistula (DAVF) generally refers to a vascular malformation of the wall of a major venous sinus. These lesions have diverse symptoms according to the location and venous drainage, and require multidisciplinary treatment. We report on our experience and analyze the treatment outcome of intracranial DAVFs for a nine-year period. METHODS: Between January 2000 and December 2008, 95 patients with intracranial DAVFs were enrolled in this study. A retrospective review of clinical records and imaging studies of all patients was conducted. Endovascular embolization, surgical interruption, gamma knife stereotactic radiosurgery (GKS), or combinations of these treatments were performed based on clinical symptoms, lesion location, and venous drainage pattern. RESULTS: Borden type I, II, and III were 34, 48, and 13 patients, respectively. Aggressive presentation was reported in 6% of Borden type I, 31% of Borden type II, and 77% of Borden type III DAVFs, respectively, and DAVFs involving transverse, sigmoid, and superior sagittal sinus. Overall, the rate of complete obliteration was 68%. The complete occlusion rates with a combination treatment of endovascular embolization and surgery, surgery alone, and endovascular embolization were 89%, 86%, and 80%, respectively. When GKS was used with embolization, the obliteration rate was 83%, although it was only 54% in GKS alone. Spontaneous obliteration of the DAVF occurred in three patients. There were a few complications, including hemiparesis (in microsurgery), intracranial hemorrhage (in endovascular embolization), and facial palsy (in GKS). CONCLUSION: The hemorrhagic risk of DAVFs is dependent on the location and hemodynamics of the lesions. Strategies for treatment of intracranial DAVFs should be decided according to the characteristic of the DAVFs, based on the location and drainage pattern. GKS can be used as an optional treatment for intracranial DAVFs.
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We present a case of an athetoid cerebral palsy with quadriparesis caused by kyphotic deformity of the cervical spine, severe spinal stenosis at the cervicomedullary junction, and atlantoaxial instability. The patient improved after the first surgery, which included a C1 total laminectomy and C-arm guided righ side unilateral C1-2 transarticular screw fixation. C1-2 fixation was not performed on the other side because of an aberrant and dominant vertebral artery (VA). Eight months after the first operation, the patient required revision surgery for persistent neck pain and screw malposition. We used intraoperative VA angiography with simultaneous fluoroscopy for precise image guidance during bilateral C1-2 transarticular screw fixation. Intraoperative VA angiography allowed the accurate insertion of screws, and can therefore be used to avoid VA injury during C1-2 transarticular screw fixation in comorbid patients with atlantoaxial deformities.
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OBJECTIVE: The purpose of this study is to verify the usefulness of autograft versus allograft in the radiographic and clinical outcome in early period after the surgery. METHODS: We performed a retrospective review of 38 patients who had undergone one- or two-level anterior cervical discectomy and fusion (ACDF) with rigid anterior plate fixation from March 2006 to May 2009. Interbody graft materials were iliac autograft (n=17) or with allograft (n=21). Fusion rate and graft collapse rate were assessed by radiographic analysis and clinical outcome was based on Odom's criteria. RESULTS: In autograft group, 13 patients achieved successful bone fusion (65%), whereas 7 patients (31.8%) in allograft group. There was statistically significant between two groups (p<0.05). Comparing immediate postoperative radiograph with last follow-up, the mean graft collapse was noted 1.3mm(15.5% change) in autograft group, whereas 2.0mm(24.7% change) in allograft group. There was no statistically significant collapse rate in autograft group (p>0.05), but statistically significant in allograft group (p<0.05). Clinical outcome was excellent or good in 94.1% in autograft group, and 90.5% in allograft group. CONCLUSION: In study, anterior cervical interbody fusion with an allograft got a result of lower fusion rate and higher collapse rate compared with autograft in early period after surgery, and clinical outcome showed similar results in both groups.
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OBJECTIVE: Recurrent lumbar disc herniation has been defined as disc herniation at the same level, regardless of ipsilateral or contralateral herniation, with a pain-free interval greater than 6 months. The aim of this study is to analyze outcomes and identify the potential risk factors for recurrent lumbar disc herniation. METHODS: The authors retrospectively reviewed the cases of 178 patients who underwent open discectomy for single-level lumbar disc herniation. Visual analogue scales and modified Macnab criteria were used to compare the clinical outcomes between the recurrent group and the non-recurrent group. Sex, age, discectomy level, degree of disc degeneration, type of disc herniation, pain-free interval after first-operation, smoking status, and trauma were investigated as potential recurrence risk factors. RESULTS: Of the 178 patients for whom the authors were able to definitely assess symptomatic recurrence status, 18 patients (10.1%) underwent revision surgery for recurrent disc herniation. The most common level involved was L4-L5 (61%) and the mean period of time to recurrence was 18.7 months (6-61 months). There were 17 cases of ipsilateral herniation and 1 case of contralateral herniation. The types of herniation for which revision surgery was done were protrusion (3 cases), and transligamentous extrusion (14 cases). There were five excellent, eight good, and two fair results. CONCLUSION: Repeated discectomy for recurrent disc herniation produced unsatisfactory outcomes. Factors such as sex, type of disc herniation and traumatic events were found to be significant risk factors.
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Spontaneous cervical epidural hematoma (SCEH) is a rare clinical entity and has a varied etiology. Urgent surgical decompression should be done to prevent serious permanent neurologic deficits. We describe a 59-year-old female who presented with Brown-Sequard syndrome due to spontaneous cervical epidural hematoma. Initially, she was misdiagnosed as cerebrovascular accident. Cervical magnetic resonance imaging revealed epidural hematoma to the right of the spinal cord extending from C3 to C6. She later underwent surgical evacuation and had complete restoration of neurologic function. The outcome in SCEH is essentially determined by the time taken from onset of the symptom to operation. Therefore, early and precise diagnosis such as careful history taking and MRI evaluation is mandatory.
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Most influenza vaccines target hemagglutinin (HA) in order to protect the host against infection. However, theses vaccines are strain-specific due to major antigenic variations of HA. Since it is difficult to predict epidemic and pandemic strains of influenza virus, the development of effective vaccines against divergent influenza viruses is urgently needed. Although M2e-based vaccines are associated with weaker protection than HA-based vaccines that induce neutralizing antibodies against challenge virus matched-strain, the extracellular domain of Matrix 2 protein (M2e) is one of a potential broad-spectrum immunogen because it contains highly conserved sequences among influenza A viruses. In this study, M2e sequence was fused to H1N1 HA DNA (M2e-HA) and the immunogenicity and antiviral efficacy of this DNA vaccine was evaluated in response to challenge with a heterosubtypic H5N2 avian influenza virus. Compared to vaccination with HA or M2e DNA alone, vaccination with M2e-HA DNA or combination of M2e DNA and HA DNA (M2e DNA+HA DNA) induced a broad immunity without evidence of immune interference. In addition, HA-specific CD8(+) and M2e-specific T cell responses elicited by M2e-HA DNA vaccination were significantly higher than those of HA or M2e DNA vaccine alone, respectively. Following challenge with a heterosubtypic influenza virus infection, vaccination with M2e-HA DNA conferred complete protection against mortality. In combination, these results suggest that DNA vaccines expressing a fusion protein, M2e-HA, may provide an attractive approach for the development of broad-spectrum influenza vaccines.
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Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Subtipo H1N1 del Virus de la Influenza A/inmunología , Subtipo H5N2 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Infecciones por Orthomyxoviridae/prevención & control , Vacunas Sintéticas/inmunología , Proteínas de la Matriz Viral/inmunología , Animales , Modelos Animales de Enfermedad , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H5N2 del Virus de la Influenza A/genética , Vacunas contra la Influenza/administración & dosificación , Vacunas contra la Influenza/genética , Leucocitos Mononucleares/inmunología , Ratones , Ratones Endogámicos BALB C , Infecciones por Orthomyxoviridae/inmunología , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/inmunología , Enfermedades de los Roedores/inmunología , Enfermedades de los Roedores/prevención & control , Análisis de Supervivencia , Subgrupos de Linfocitos T/inmunología , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/genética , Proteínas de la Matriz Viral/genéticaRESUMEN
OBJECTIVE: Paraclinoid segment internal carotid artery (ICA) aneurysms have historically been a technical challenge for neurovascular surgeons. The development of microsurgical approach, advances in surgical techniques, and endovascular procedures have improved the outcome for paraclinoid aneurysms. However, many authors have reported high complication rates from microsurgical treatments. Therefore, the present study reviews the microsurgical complications of the extradural anterior clinoidectomy for treating paraclinoid aneurysms and investigates the prevention and management of observed complications. METHODS: Between January 2004 and April 2008, 22 patients with 24 paraclinoid aneurysms underwent microsurgical direct clipping by a cerebrovascular team at a regional neurosurgical center. Microsurgery was performed via an ipsilateral pterional approach with extradural anterior clinoidectomy. We retrospectively reviewed patients' medical charts, office records, radiographic studies, and operative records. RESULTS: IN OUR SERIES, THE CLINICAL OUTCOMES AFTER AN IPSILATERAL PTERIONAL APPROACH WITH EXTRADURAL ANTERIOR CLINOIDECTOMY FOR PARACLINOID ANEURYSMS WERE EXCELLENT OR GOOD (GLASGOWS OUTCOME SCALE : GOS 5 or 4) in 87.5% of cases. The microsurgical complications related directly to the extradural anterior clinoidectomy included transient cranial nerve palsy (6), cerebrospinal fluid leak (1), worsened change in vision (1), unplanned ICA occlusion (1), and epidural hematoma (1). Only one of the complications resulted in permanent morbidity (4.2%), and none resulted in death. CONCLUSION: Although surgical complications are still reported to occur more frequently for the treatment of paraclinoid aneurysms, the permanent morbidity and mortality resulting from a extradural anterior clinoidectomy in our series were lower than previously reported. Precise anatomical knowledge combined with several microsurgical tactics can help to achieve good outcomes with minimal complications.