Kazunari Kogure

Differential role of TNF-α and IFN-γ in the brain of rats with chronic relapsing autoimmune encephalomyelitis

Abstract To elucidate the mechanisms of relapses of the clinical signs in experimental autoimmune encephalomyelitis (EAE), the cytokine profile of chronic relapsing EAE (CR-EAE) in rats was determined by competitive polymerase chain reaction (PCR). By immunization with guinea pig spinal cord homogenate and treatment with low-dose cyclosporin A (CsA), rats developed two attacks of EAE with remission in between. Cytokine analysis revealed that the level of TNF-α mRNA increased at the first and second attacks with transient disappearance at the remission phase. In contrast, the level of IFN-γ mRNA was suppressed at the first attack by CsA and peaked at the second attack. Intraventricular administration of IFN-γ prior to onset of disease signs induced more relapses, or a severe lethal form. In addition, the intraventricular injection of TNF-α caused the persistence of the clinical signs. These findings suggest that TNF-α contributes to the first and second attacks of CR-EAE, while IFN-γ is not required for the first attack but is closely related to the relapse of the disease. With regard to anti-inflammatory cytokines, the levels of both TGF-β1 and IL-10 mRNA at the second attack were higher than those at the first attack. Taken together, differential involvement of TNF-α and IFN-γ is closely associated with the clinical features of CR-EAE.

Surgical Pitfalls of an Ultrasonic Bone Curette (Sonopet) in Spinal Surgery

OBJECTIVE: We report our experience with the SONOPET ultrasonic bone curette. METHODS: Between September 2001 and July 2005, 546 patients underwent microscopic spinal surgeries using a high-speed drill and the SONOPET instrument. RESULTS: We encountered operative complications thought to be attributable to the use of the SONOPET in six patients (1.1%). There were five instances of dural puncture and one spinal cord injury. All dural tears occurred when the dura mater was aspirated into the tip of the SONOPET. None of the affected patients developed postoperative clinical complications because cerebrospinal fluid leakage was avoided by appropriate closure. We think that the transient spinal cord injury occurred because the vibration emanating from the SONOPET was transmitted directly to the spinal cord. Some patients experienced damage to the epidural venous plexus for reasons similar to those described above. CONCLUSION: SONOPET facilitates the removal of bone in a narrow field, such as that encountered during keyhole surgery. It aids in the removal of the lateral edge of bone and is especially useful for expanding the foramen intervertebrale or opening the lateral recess. However, its use is not without risk. To prevent dural tears and venous plexus injury, we recommend that cotton be placed between the SONOPET and important structures. To avoid spinal cord injury, we suggest that the SONOPET be inserted horizontal with the dura mater to avoid the direct transmission of vibrations emanating from the instrument to the spinal cord. SONOPET is suitable for decompression on the lateral side, but not for decompression above the spinal cord.

Surgical pitfalls of an ultrasonic bone curette (SONOPET) in spinal surgery. Commentary

OBJECTIVE: We report our experience with the SONOPET ultrasonic bone curette. METHODS: Between September 2001 and July 2005, 546 patients underwent microscopic spinal surgeries using a high-speed drill and the SONOPET instrument. RESULTS: We encountered operative complications thought to be attributable to the use of the SONOPET in six patients (1.1%). There were five instances of dural puncture and one spinal cord injury. All dural tears occurred when the dura mater was aspirated into the tip of the SONOPET. None of the affected patients developed postoperative clinical complications because cerebrospinal fluid leakage was avoided by appropriate closure. We think that the transient spinal cord injury occurred because the vibration emanating from the SONOPET was transmitted directly to the spinal cord. Some patients experienced damage to the epidural venous plexus for reasons similar to those described above. CONCLUSION: SONOPET facilitates the removal of bone in a narrow field, such as that encountered during keyhole surgery. It aids in the removal of the lateral edge of bone and is especially useful for expanding the foramen intervertebrale or opening the lateral recess. However, its use is not without risk. To prevent dural tears and venous plexus injury, we recommend that cotton be placed between the SONOPET and important structures. To avoid spinal cord injury, we suggest that the SONOPET be inserted horizontal with the dura mater to avoid the direct transmission of vibrations emanating from the instrument to the spinal cord. SONOPET is suitable for decompression on the lateral side, but not for decompression above the spinal cord.

Quantitative analysis of pro- and anti-inflammatory cytokine mRNA in neural graft rejection

The central nervous system (CNS) has been considered an immunologically privileged site. However, this concept is now changing because rejection of histoincompatible neural grafts is commonly observed in the CNS. To be able to use neural transplantation as therapy for human diseases, it is important to determine factors that are related to brain-graft rejection. In the present study, we examined the phenotype of infiltrating T cells around grafts in the cerebra that had received xenogeneic (mouse to rat) neural transplants. Furthermore, the amount of pro- and anti-inflammatory cytokine mRNA was determined by competitive PCR at various time points after the neural transplantation. Immunohistochemical examination revealed that both CD4-positive and CD8-positive T cells infiltrated the CNS parenchyma. In competitive PCR analysis, levels of IFN-gamma and perforin in xenografts on days 10 and 13 post-transplantation (PT) were higher than those in isografts (rat to rat) at the same stage, whereas the levels of TNF-alpha, which was detected only on day 7 PT, were not significantly different between the two groups. With regard to anti-inflammatory cytokines, TGF-beta1 mRNA was recognized throughout the examination period, but there was no significant difference between xeno- and iso-grafts at most time points. These findings suggest that IFN-gamma and perforin secreted by infiltrating CD4-positive and CD8-positive T cells, respectively, play an important role in neural graft rejection. The responses of anti-inflammatory cytokines seem to be nonspecific reactions to grafts or surgical procedures.

Indwelling Drains Are Not Necessary for Patients Undergoing One-level Anterior Cervical Fixation Surgery

BACKGROUND Anterior cervical discectomy and fusion (ACDF) has become a common procedure for cervical spine surgeries, since it is safe and effective in most patients. However, some patients develop life-threatening problems such as respiratory obstruction arising from rare postoperative hematoma and edema, although intraoperative bleeding caused by the connective tissue splitting procedure or bleeding caused by postoperative insertion of a suction tube has rarely been reported. Investigation of the requirement for indwelling drains in patients who undergo cervical spine surgery is necessary because of the pain, anxiety, and discomfort caused despite the use of high-quality materials. METHODS Enrolled in the study were 43 patients who underwent one-level anterior cervical fixation surgery, including 23 (randomly selected) who received an indwelling drain (group A, mean age: 57.78±14.46 years, range: 39-82 years, male/female: 13/10), and 20 who received no indwelling drain (group B, mean age: 57.00±13.99 years, range: 29-81 years, male/female: 12/8). Intraoperative bleeding amounts, lateral views of plain cervical spine radiographs, prevertebral space (PVS) changes on plain radiographs and computed tomography (CT) images, wound inspections, and pain assessments on the Numeric Rating Scale (NRS) were compared between groups. In addition, a history of risk factors for bleeding, such as hypertension, diabetes, and cerebrovascular diseases which require antiplatelet therapy, was determined. Hepatic failure was observed in none of the patients. RESULTS Postoperative CT images obtained the day following surgery showed no densities indicating the presence of postoperative hematoma in any of the 43 patients. The maximum amount of intraoperative bleeding was 10 mL, with no significant difference between groups. No patients reported an obvious pain level on NRS, but the pain was significantly milder in group B (A: 1.326±0.911, B: 0.555±0.556, p=0.0037). The postoperative PVS increment on plain radiographs was comparable between groups (A: 1.778±0.992, B: 1.730±0.966, p=0.8728). DISCUSSION Given the negligible intraoperative and postoperative bleeding observed in both groups, and the lack of difference in PVS increments between the groups, our results suggested that indwelling drains are not required for patients undergoing typical anterior cervical fixation surgery. However, it is important to take care of major vessels such as the superior and inferior thyroid arteries and the external jugular vein as well as the prevertebral venous plexus during surgery.

Technical Arrangement of the Williams-Isu Method for Anterior Cervical Discectomy and Fusion

Anterior cervical fixation with autologous bone transplantation-without the need for harvesting bone from other sites, such as the ilium-was developed by Williams and modified by Isu et al. In recent intervertebral fusion procedures, after harvesting the cuboid bone from vertebral bodies, a hydroxyapatite block is placed between two harvested vertebral bones in the same way as in the sandwich method for intervertebral fixation. According to previous studies, this procedure has the following disadvantages: (i) as the corrective force for cervical kyphosis is insufficient, it could not be adapted for patients with preoperative kyphosis; (ii) special devices, including a microsurgical saw, are required for harvesting vertebral bones. In our modified method, we used a conventional high-speed drill instead of a microsurgical saw. Nevertheless, the results show that the operated spine can be stabilized to a greater extent by decreasing the height of the grafted bone, and this might help in reducing postoperative kyphosis.

Neck and Occipital Pain Caused by Deep Cervical Intramuscular Lipoma: A Surgical Case

A lipoma is a slow-growing, benign tumor and is usually asymptomatic; hence, surgical intervention can often be avoided in patients with these tumors in the cervical and cranial area. Lipomas arise most commonly in the subcutaneous fat, but occasionally in muscle tissue. Intramuscular lipomas in the cervico-cranial area have rarely been reported. We describe here a patient with a large intramuscular lipoma in the deep cervical tissue. The patient experienced troublesome pain in the neck and occipital area, and surgical treatment was therefore suggested. Particularly in the cervical area, intramuscular lipomas sometimes invade the surrounding muscles and tissue layers and develop into an irregular mass, despite being benign. In addition, the cervical area has one of the most complex muscle structures. Nevertheless, surgical management of intramuscular lipoma in the cervical and cranial area is sometimes indicated, for example, in patients with clinical symptoms or masses with a tendency to grow large.