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Objectives: Given the high prevalence of fast-metabolizing alcohol dehydrogenase-1B*2 (ADH1B*2 ) and inactive aldehyde dehydrogenase-2*2 (ALDH2*2 ) alleles in East Asians, we evaluated how the ADH1B / ALDH2 genotypes and alcohol flushing might affect the development of alcohol dependence (AD)., Methods: We evaluated how the ADH1B / ALDH2 genotypes and self-reported alcohol flushing affected history of drinking events and withdrawal symptoms and ICD-10 criteria in 4116 Japanese AD men., Results: The ADH1B*1/*1 group and ALDH2*1/*1 group were 1-5 years younger than the ADH1B*2 (+) and ALDH2*1/*2 groups, respectively, for all of the ages at onset of habitual drinking, blackouts, daytime drinking, uncontrolled drinking, withdrawal symptoms, and first treatment for AD, and the current age. Blackouts were more common in the ADH1B*1/*1 group and ALDH2*1/*1 group. Daytime drinking, uncontrolled drinking, and withdrawal symptoms, such as hand tremor, sweating, convulsions, and delirium tremens/hallucinations were more common in the ADH1B*1/*1 group. The ADH1B*1/*1 was positively associated with the ICD-10 criteria for 'tolerance' and 'withdrawal symptoms'. The ADH1B*1/*1 group and ALDH2*1/*2 group had a larger ICD-10 score. Never flushing was reported by 91.7% and 35.2% of the ALDH2*1/*1 and ALDH2*1/*2 carriers, respectively. After a 1-2-year delay in the onset of habitual drinking in the former-/current-flushing group, no differences in the ages of the aforementioned drinking milestones were found according to the flushing status., Conclusion: The ADH1B*1/*1 and ALDH2*1/*1 accelerated the development of drinking events and withdrawal symptoms in Japanese AD patients. ICD-10 score was larger in the ADH1B*1/*1 group and ALDH2*1/*2 group. The effects of alcohol flushing on drinking events were limited., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Subconjunctival herniated orbital fat (SHOF) usually occurs in the superotemporal quadrant, and SHOF located in other quadrants is extremely rare. This study aimed to compare the patient characteristics between patients with SHOF in the superotemporal quadrant and those with SHOF in other quadrants. This is a retrospective study of 45 patients with SHOF who were referred to our institution between January 2015 and January 2023 and 14 previously reported patients in published case reports of SHOF that were not located in the superotemporal quadrant. Data on patient age, sex, affected sides, and body mass index were collected from the medical records of our institution and from previous reports. Patient age, male-to-female ratio, unilateral-to-bilateral ratio, and body mass index were compared between patients with SHOF in the superotemporal quadrant and patients with SHOF in the other quadrants. Of the 45 patients, only 1 patient showed SHOF in a location other than the superotemporal quadrant (inferonasal quadrant). Based on a comparison of 44 patients with SHOF in the superotemporal quadrant and 15 patients with SHOF in the other quadrants, the latter entity predominantly occurred in young, non-obese females (P < .050). Unilateral cases were more common in SHOF in the other quadrants (P = .003). Patient characteristics were found to be different between cases of SHOF in the superotemporal quadrant and those with SHOF in the other quadrants., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Abstract: In addition to advanced non-small cell lung cancer, nanoparticle albumin-bound paclitaxel (nab-PTX) may also harbor potential benefit for patients with relapsed small cell lung cancer (SCLC), since weekly paclitaxel (PTX) shows modest activity for relapsed SCLC. We evaluated the efficacy and safety of both weekly nab-PTX and PTX for relapsed SCLC.We retrospectively reviewed 52 consecutive relapsed SCLC patients who were treated with weekly nab-PTX or PTX at our hospital.The response rate, median progression-free survival and overall survival with nab-PTX and PTX were 5.6 vs 8.8%, 3.2 vs 1.7 months, and 5.4 vs 4.5 months, respectively. No statistically significant differences were observed. There was no statistical difference between the 2 groups for ≥Grade 3 adverse events.Weekly nab-PTX and PTX showed similar activity for relapsed SCLC. The toxicity profile of nab-PTX was equally tolerable to that of PTX., Competing Interests: Masahiro Morise reports personal fees and other from Taiho, grants and personal fees from Boehringer-ingelheim, personal fees from Daiichi Sankyo, grants and personal fees from Eli Lilly, personal fees and other from Chugai, personal fees and other from Astra Zeneca, personal fees and other from Ono, personal fees and other from Pfizer, personal fees and other from MSD, other from Merk serono, other from Kissei, other from Novartis, other from Roche, outside the submitted work. Yasuhiro Kondoh serves as a consultant to Asahi Kasei Pharma Corp., Shionogi & Co. Ltd., Boehringer Ingelheim Co., Ltd., Janssen Pharmaceutical K.K., Healios K.K., Chugai Pharmaceutical Co., Ltd., and Taiho Pharmaceutical Co., Ltd., received lecture fees from Asahi Kasei Pharma Corp., Shionogi & Co. Ltd., and Boehringer Ingelheim Co., Ltd., Astra Zeneca K.K, Eisai Inc., KYORIN Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma, and Novartis Pharma K.K., outside the presentation work; the others have no conflict of interest., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Study Design: A multicenter, retrospective study., Objective: To clarify the clinical and radiological effects of removing interspinous contextures in lumbar decompression surgery for patients with lumbar spinal stenosis., Summary of Background Data: There have seldom been reports that have compared both clinical results and radiological changes among minimally invasive decompression methods., Methods: Consecutive 52 patients underwent lumbar spinous process-splitting laminectomy (LSPSL), following which 50 patients underwent trans-interspinous lumbar decompression (TISLD). All patients presented with cauda equina type of lumbar spinal stenosis and underwent a minimum 1-year follow-up. The Japanese Orthopaedic Association (JOA) score and Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) score were evaluated to determine the extent of daily living activities. Propensity score (PS)-matched analysis was used to match patients' age and preoperative JOA scores between the two groups. Lumbar lordosis (LL), disc height (DH), segmental range of motion (ROM), and vertebral anterior translation were measured by functional lumbar lateral x-ray, and changes between preoperative and 1-year postoperative values were evaluated., Results: Twenty-nine pairs of patients were selected by PS-matching. Mean JOA scores increased from 14.4 to 23.5 (mean recovery rate was 62.3%) in the LSPSL group and from 14.0 to 23.2 (61.3%) in the TISLD group at preoperative and 1-year follow-up, respectively. There were no significant differences in clinical results and changes in LL, ROM, and vertebral anterior translation in each group. The DH at L4/5 level at 1-year after surgery revealed significant decrease in the TISLD group compared with the LSPSL group. There was a correlation between preoperative DH and DH decrease in the LSPSL group, but not in TISLD group., Conclusion: Removal of interspinous contextures did not influence clinical outcomes at 1 year after surgery, but it may be likely to cause disc height loss when it applied at the L4/5 level.Level of Evidence: 3., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Study Design: A retrospective comparison of the surgical outcome after cervical laminoplasty for cervical spondylotic myelopathy (CSM) using a modified K-line based on lordosis in neck extension as a predictor: in K-line Back CSM (KB group), the K-line crosses the ventral edge of any of the spinous processes, whereas in K-line Front CSM (KF group), the K-line does not., Objective: To investigate the neurological and radiological outcomes 5 years after surgery and the contact between the spinal cord and posterior elements after laminoplasty for CSM using the modified K-line., Summary of Background Data: No indicators on a lateral radiograph can predict the neurological outcome after laminoplasty for CSM., Methods: Patients with CSM were divided into KB (n = 20) and KF groups (n = 13). We compared the postoperative Japanese Orthopedic Association (JOA) score, recovery rate, grip-and-release and foot-tapping test results, alignment, and contact between the spinal cord and posterior elements between the two groups., Results: The postoperative JOA score and its recovery rate were significantly lower in the KB group (12.4 points and 34.1%, respectively) than in the KF group (14.1 points and 59.0%, respectively) at final follow-up (P = 0.0415 and 0.0458). The grip-and-release and foot-tapping test results improved significantly in the KF group but not in the KB group. In the KB group, a larger lordotic angle in extension at 1 year postoperatively continued until final follow-up. The rate of recovery of the JOA score in patients with contacts at both C4/5 and C5/6 and any contact in the KB group (-1.5% and 31.9%, respectively) were lower (P = 0.0013 and 0.0534, respectively) than those in the KF group (58.6% and 60.7%, respectively)., Conclusion: The K-line Back predicts a poor neurological outcome after laminoplasty for CSM. Decompression with fusion may be recommended for these patients.Level of Evidence: 4., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This study sought to evaluate the impacts of interactions between the alcohol dehydrogenase-1B (rs1229984) genotype and the aldehyde dehydrogenase-2 (rs671) genotype on alcohol flushing, alcohol reeking on the day after drinking, and the age distribution in alcohol-dependent patients., Methods: The study subjects were 4107 Japanese alcohol-dependent men who underwent alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 genotyping: 4051 patients were asked about their current or former tendency to experience facial flushing after drinking a glass of beer, and 969 patients were asked about whether they had ever been told that they reeked of alcohol more than 12 hours after they had stopped drinking., Results: Current, former, and never flushing were reported in 3.5, 14.9, and 81.5%, respectively, of the subject, and alcohol reeking after more than 12 hours in 36.1% of the subjects. The fast-metabolizing ADH1B*2(+) genotype (*1/*2 or *2/*2) and the inactive ALDH2*2(+) genotype (*1/*2 or *2/*2) affected the multivariate odds ratios for current or former flushing [odds ratio, 95% confidence interval = 2.27 (1.79-2.86) and 23.0 (18.6-28.5), respectively, vs. *2(-) genotype] and for alcohol reeking [0.39 (0.29-0.52) and 1.56 (1.09-2.25), respectively, vs. *2(-) genotype]. An age-dependent decrease in the ADH1B*2(-) and ALDH2*2(-) combination from 32.3% in the 30-39-year age group to 12.5% in the 70-79-year age group and an age-dependent increase in the ADH1B*2(+) and ALDH2*2(-) combination from 52.5% in the 30-39-year age group to 70.5% in the 70-79-year age group were observed (P < 0.0001 for trend). The frequencies of the ADH1B*2(-) and ALDH2*2(+) combination (4.7-6.2%) and the ADH1B*2(+) and ALDH2*2(+) combination (8.9-12.0%) did not change markedly with increasing age., Conclusion: Interactions between the alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 genotypes modified alcohol flushing, alcohol reeking on the day after drinking, and the age distribution. These findings support the protective roles of the ADH1B*2(+) and ALDH2*2(+) genotypes against the development of alcohol dependence.

Background: Noninvasive blood-pressure measurement device and pulse oximeter are important for patient monitoring. When these are placed on the same side, cuff inflation sometimes causes measurement failure by pulse oximeter., Objective: The present study aimed to compare the pulse oximeter alarm frequency and pulse-wave disappearance duration between noninvasive blood-pressure measurement using the deflation method and that using the linear inflation method., Methods: The study included 10 healthy subjects. The cuff for automatic sphygmomanometer was wrapped on one side of the upper arm and for pulse oximeter was attached to the thumb of the same side of upper limbs., Results: The alarm frequency was 0 and 26% using the linear inflation and the deflation methods, respectively. Additionally, the pulse-wave disappearance duration was significantly longer using the deflation method than that using the linear inflation method (10.0 ± 1.5 vs 1.7 ± 0.8 s). With the linear inflation method, this duration was or less 3 s. In the deflation method, an excess pressure of 40 mmHg was used, which caused the alarm to turn on. Additionally, the heart rate was found to influence the alarm occurrence during measurement using the deflation method., Conclusion: Heart rate may influence alarm occurrence during blood-pressure measurement using the step deflation method. Using the linear inflation method, the risks of alarm occurrence and measurement failure are low, even when the pulse oximeter and blood-pressure measurement cuffs are installed on the same side, suggesting that this method is suitable for clinical use.

In young children, infrequent antigen exposure, which is partly characterized by fewer vaccinations, may be a factor impairing the immunogenicity of inactivated influenza vaccine.We assessed the effects of prior vaccinations on age-specific immune responses in Japanese children aged 6 months to 3 years, using data from a cohort study with 266 children who had received 2 doses (0.25 mL/dose for < 3 years old, 0.5 mL/dose for 3 years old) in the 2006/2007 season. Serological measures, primarily seroprotection rates, between previously vaccinated and vaccine-naïve children were compared within 1-year age strata. The seroprotection rate was defined in 2 ways as the proportion of subjects who achieved an antibody titer of 1:40 or 1:160. Multivariate logistic regression was also performed to estimate the independent effect of prior vaccination on seroprotection rate.After the first dose, seroprotection rates with the threshold of 1:40 in vaccine-naïve 1-year-olds remained low (28% for AH1, 26% for AH3, 2% for B), similar to those of 0-year-olds. In contrast, seroprotection rates in previously vaccinated 1-year-olds (77% for AH1, 86% for AH3, 18% for B) were significantly higher than those in vaccine-naïve 1-year-olds. These seroprotection rates for AH1 and AH3 were comparable with those in previously vaccinated 2- and 3-year-olds. Although seroprotection rates for B remained low in every age stratum even after the second dose, seroprotection rate in previously vaccinated 1-year-olds (50%) was similar to that in 3-year-olds. After adjustment for age, baseline antibody titer and experience of acute febrile respiratory illness in the preceding season, odds ratios showed a significant independent positive effect of prior vaccination on seroprotection rate for every strain. After the seroprotection threshold was changed from 1:40 to 1:160, the results of the effects of prior vaccinations on immunogenicity were similar or became more evident, which demonstrate the robustness of our findings.Our study found that prior vaccinations improved poor immunogenicity among young children, especially in 1-year-olds.

Rationale: Neurogenic shock is generally typified by spinal injury due to bone metastases in cancer patients, but continuous disturbance of the vagus nerve controlling the aortic arch baroreceptor can cause shock by a reflex response through the medulla oblongata., Patient Concerns: A 43-year-old woman with dysphagia presented to our hospital. Computed tomography showed a primary tumor adjacent to and surrounding half the circumference of the descending aorta, and multiple cervical lymph node metastases, including a 55 × 35-mm lymph node overlapping the root of the left vagus nerve. Squamous esophageal cancer (T4bN3M1, stage IV) was diagnosed. Whereas shock status initially appeared soon after left cervical pain, suggesting pain-induced neutrally-mediated syncope, sustained bradycardia and hypotension occurred even after alleviation of pain by opioids., Diagnosis: Disturbance of the left vagus nerve associated with the aortic arch baroreceptor by a large left cervical lymph node metastasis was considered as the cause of shock, pathologically mimicking the baroreceptor reflex., Interventions: Systemic steroid administration was performed, and radiotherapy for both the primary site and lymph node metastasis was started 2 days after initiating steroid treatment., Outcomes: Four days after initiating steroid administration, hypotension and bradycardia were improved and stable., Lessons: Disturbance of the vagus nerve controlling the aortic arch baroreceptor should be kept in mind as a potential cause of neurogenic shock in cancer patients, through a pathological reflex mimicking the baroreceptor reflex.

In Japan, the routine immunization program with oral polio vaccine (OPV) has been suspended since September 2012, when a program with 4 doses of inactivated monovalent polio vaccine (IPV) or quadrivalent vaccine against diphtheria, pertussis, and tetanus with IPV (DTaP-IPV) was introduced. The aim of this study was to examine the interchangeability among these 3 types of polio vaccines.We conducted a prospective cohort study at 5 pediatric clinics in Japan. A total of 153 infants were assigned to 1 of the 4 groups by considering the vaccination history of OPV and trivalent vaccine against DTaP. Eleven infants with a history of OPV received 3 doses of DTaP-IPV; 49 infants with a history of OPV and DTaP received 3 doses of IPV; 50 polio vaccine-naïve infants received 2 doses of IPV followed by 2 doses of DTaP-IPV; and 43 polio vaccine-naive infants received 2 doses of DTaP-IPV followed by IPV. The immunogenicity after polio vaccination was evaluated among these 4 groups.After 2 doses of polio vaccination, more than 80% of the infants exhibited a neutralization antibody titer ≥1:8 for all Sabin strains and wild strains in all groups. After the third dose, the seroprotection proportion (i.e., a neutralization antibody titer ≥1:8) reached about 100%. After the fourth dose, a neutralization antibody titer exceeded the required protective levels (i.e., a neutralization antibody titer ≥1:8) considerably in all groups.Four doses of polio vaccines induced a sufficient level of immunity in Japanese infants, irrespective of vaccine combinations or order.

Study Design: Retrospective study comparing postoperative clinical outcomes after cervical laminoplasty between K-line (-) ossification of the posterior longitudinal ligament (OPLL) and K-line (+) OPLL in the neck-flexed position., Objective: To investigate postoperative outcomes using Japanese Orthopedic Association (JOA) scores, and grip-and-release (GR) and foot-tap (FT) test scores after laminoplasty in patients with K-line (-) OPLL in the neck-flexed position., Summary of Background Data: Cervical laminoplasty has been reported to lead to poor outcomes in K-line (-) OPLL and good outcomes in K-line (+) OPLL. The cervical spine, however, continues moving in the extension and flexion direction after laminoplasty., Methods: Patients with cervical myelopathy were divided into K-line (+) and (-) in the neck-flexed position. We compared postoperative outcomes after cervical laminoplasty using recovery rate, as assessed by the JOA score and degree of improvement in the six JOA score items, and performance, as assessed by GR and (FT) tests, between patients with K-line (+) OPLL (n = 18) and K-line (-) OPLL (n = 23) in the neck-flexed position., Results: Recovery rate of JOA score (23.8%) of patients in the K-line (-) group was significantly lower (P = 0.028) than that (46.3%) of K-line (+) group in the neck-flexed position. In the K-line (+) group, significant improvements were seen in all JOA-score items except bladder function; however, in the K-line (-) group, improvements were seen only in upper- and the lower-extremity sensory functions. In the K-line (+) group, mean GR and FT tests significantly improved, but in the K-line (-) group, only mean FT test significantly improved., Conclusion: The K-line (-) OPLL in the neck-flexed position is a risk factor for poor clinical outcome after cervical laminoplasty., Level of Evidence: 4.

Background: The transient receptor potential vanilloid 1 (TRPV1) and the transient receptor potential ankyrin 1 (TRPA1), which are expressed in sensory neurons, are polymodal nonselective cation channels that sense noxious stimuli. Recent reports showed that these channels play important roles in inflammatory, neuropathic, or cancer pain, suggesting that they may serve as attractive analgesic pharmacological targets. Tramadol is an effective analgesic that is widely used in clinical practice. Reportedly, tramadol and its metabolite (M1) bind to μ-opioid receptors and/or inhibit reuptake of monoamines in the central nervous system, resulting in the activation of the descending inhibitory system. However, the fundamental mechanisms of tramadol in pain control remain unclear. TRPV1 and TRPA1 may be targets of tramadol; however, they have not been studied extensively., Methods: We examined whether and how tramadol and M1 act on human embryonic kidney 293 (HEK293) cells expressing human TRPV1 (hTRPV1) or hTRPA1 by using a Ca imaging assay and whole-cell patch-clamp recording., Results: Tramadol and M1 (0.01-10 μM) alone did not increase in intracellular Ca concentration ([Ca]i) in HEK293 cells expressing hTRPV1 or hTRPA1 compared with capsaicin (a TRPV1 agonist) or the allyl isothiocyanate (AITC, a TRPA1 agonist), respectively. Furthermore, in HEK293 cells expressing hTRPV1, pretreatment with tramadol or M1 for 5 minutes did not change the increase in [Ca]i induced by capsaicin. Conversely, pretreatment with tramadol (0.1-10 μM) and M1 (1-10 μM) significantly suppressed the AITC-induced [Ca]i increases in HEK293 cells expressing hTRPA1. In addition, the patch-clamp study showed that pretreatment with tramadol and M1 (10 μM) decreased the inward currents induced by AITC., Conclusions: These data indicate that tramadol and M1 selectively inhibit the function of hTRPA1, but not that of hTRPV1, and that hTRPA1 may play a role in the analgesic effects of these compounds.

Objective: Involvement of reactive oxygen species derived from nicotinamide adenine dinucleotide phosphate, reduced form (NADPH) oxidase has been documented in the development of hypoxia-induced model of pulmonary arterial hypertension (PAH). Because the PAH-like phenotype was demonstrated in mice deficient in Nox1 gene (Nox1(-/Y)) raised under normoxia, the aim of this study was to clarify how the lack of NOX1/NADPH oxidase could lead to pulmonary pathology., Approach and Results: Spontaneous enlargement and hypertrophy of the right ventricle, accompanied by hypertrophy of pulmonary vessels, were demonstrated in Nox1(-/Y) 9 to 18 weeks old. Because an increased number of α-smooth muscle actin-positive vessels were observed in Nox1(-/Y), pulmonary arterial smooth muscle cells (PASMCs) were isolated and characterized by flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. In Nox1(-/Y) PASMCs, the number of apoptotic cells was significantly reduced without any change in the expression of endothelin-1, and hypoxia-inducible factors HIF-1α and HIF-2α, factors implicated in the pathogenesis of PAH. A significant decrease in a voltage-dependent K(+) channel, Kv1.5 protein, and an increase in intracellular potassium levels were demonstrated in Nox1(-/Y) PASMCs. When a rescue study was performed in Nox1(-/Y) crossed with transgenic mice overexpressing rat Nox1 gene, impaired apoptosis and the level of Kv1.5 protein in PASMCs were almost completely recovered in Nox1(-/Y) harboring the Nox1 transgene., Conclusions: These findings suggest a critical role for NOX1 in cellular apoptosis by regulating Kv1.5 and intracellular potassium levels. Because dysfunction of Kv1.5 is among the features demonstrated in PAH, inactivation of NOX1/NADPH oxidase may be a causative factor for pulmonary vascular remodeling associated with PAH.

Study Design: An in vitro cadaveric biomechanical study., Objective: To evaluate the anteroposterior (A-P) stability and the flexibility of our novel motion preservation device (MPD) using cadaveric cervical spines., Summary of Background Data: The MPD intended to restrict the A-P instability of the C1-C2 complex and to preserve the axial rotation, flexion, extension, and lateral bending was designed and produced. The stability and the flexibility of the MPD was evaluated., Methods: Ten embalmed cadaveric specimens were loaded with pure A-P translation force and the A-P translational distances were measured. Each specimen was tested for the following 4 models, respectively: Intact (control), the Dens-removed, the MPD instrumented, and a Rod fixation system instrumented. Fifteen specimens were loaded with pure moments (up to 1.5 Nm), and the C1-C2 range of motion (ROM) was measured for flexion, extension, lateral bending, and axial rotation using a stereophotogrammetry motion analysis system., Results: Mean A-P translational distances were 4.26 mm in Intact, 13.1 in the Dens-removed, 5.42 in the MPD, and 2.58 in the Rod fixation. The distance values with the MPD had no significant difference compared with Intact. Mean C1-C2 ROM of Intact, the MPD, and the Rod fixation at 1.5 Nm were: 14.7, 6.96, and 2.11 degrees in flexion, 6.46, 4.72, and 2.84 degrees in extension, 3.29, 4.02, and 1.01 degrees in right lateral bending, 4.92, 4.58, and 1.84 degrees in left lateral bending, 26.4, 15.4, and 1.16 degrees in right axial rotation, and 25.6, 14.3, and 1.21 degrees in left axial rotation, respectively., Conclusions: The MPD restricted the A-P instability of the C1-C2 complex. In flexion, extension, and axial rotation, the C1-C2 ROM of the MPD was about 50% of the ROM in Intact, whereas equivalent to Intact in lateral bending.

Study Design: A cadaver and clinical study investigated the attachment of the nuchal ligament to the cervical spinous process., Objective: To investigate the anatomical details of the attachment of the nuchal ligament to the spinous process and the relationship between the morphology of the nuchal ligament and postoperative axial pain after laminoplasty., Summary of Background Data: The relationship between the length of the C6 spinous process and the morphology of the nuchal ligament and occurrence of postoperative axial pain has not been elucidated., Methods: The morphology of the nuchal ligament was investigated in 35 cadavers and 60 patients on preoperative computed tomography and magnetic resonance imaging. The lengths of the C6 and C7 spinous processes were measured, and the C6:C7 ratio (C6 spinous process length/C7 spinous process length) was calculated. The relationship between the morphology of the attachment of nuchal ligament to the C6 spinous process and the C6:C7 ratio were investigated. In addition, the effects of the anatomy of the nuchal ligament around the C6 spinous process and different procedures of surgical invasion to C6 or C7 on postoperative axial pain were investigated for 113 patients who underwent laminoplasty., Results: The nuchal ligament was attached to not only the C7 spinous process, but also the C6 spinous process when the C6:C7 ratio was more than 0.8. When the nuchal ligament was attached to the C6 spinous process and to C7, postoperative axial pain after C3-C7 laminoplasty occurred more often compared with C3-C6 laminoplasty for patients without the nuchal ligament attached to the C6 spinous process., Conclusion: This study shows that there is an association between the individual anatomical differences of the nuchal ligament and the occurrence of postoperative axial pain after laminoplasty. Careful attention should be paid to the morphology of the attachment of the nuchal ligament to the C6 spinous process to reduce postoperative axial pain.

Study Design: A clinical and cohort study., Objective: The first purpose of this study was to investigate the standard value of a simple foot tapping test (FTT) in a large healthy population. The second purpose was to elucidate the validity of FTT as a quantitative assessment of lower extremity motor function for cervical compressive myelopathy., Summary of Background Data: Several clinical performance tests have been reported as objective assessments for the severity of cervical myelopathy. The FTT is the simplest and easiest method for a quantitative analysis of lower limb motor dysfunction in the upper motor neuron diseases. However, there were few studies about the FTT in cervical myelopathy., Methods: We recruited 252 patients who were diagnosed with cervical myelopathy and 792 healthy volunteers who participated in a health promotion project. Among the patients, 126 who underwent surgery were evaluated both before and 1 year after surgery. We performed the FTT and grip and release test and evaluated the modified Japanese Orthopaedic Association (JOA) score for cervical myelopathy., Results: The mean value of FTT was 23.8 ± 7.2 in myelopathic patients, which was significantly lower than 31.7 ± 6.4 in healthy controls and decreased with age. The value of FTT significantly correlated with the lower extremity motor function of modified JOA score and the value of grip and release test. Among the patients who underwent surgery, the average value of FTT was 22.4 ± 7.0 preoperatively and improved to 28.4 ± 8.1 at 1 year postoperatively. Postoperative gain of FTT significantly correlated with the gain of JOA score., Conclusion: The FTT results correlated with those of other tests for cervical myelopathy, and the FTT scores were improved by surgery. The FTT is an easy and useful quantitative assessment method for lower extremity motor function in patients with cervical myelopathy, especially those who cannot walk.

Objective: The goal of the current investigation was to examine a cohort of symptomatic and asymptomatic LRRK2 mutation carriers, in order to address whether the reported alterations in amyloid β (Aβ) and tau species in the CSF of patients with sporadic Parkinson disease (PD) are a part of PD pathogenesis, the aging process, or a comorbid disease in patients with PD, and to explore the possibility of Aβ and tau as markers of early or presymptomatic PD., Methods: CSF Aβ42, total tau, and phosphorylated tau were measured with Luminex assays in 26 LRRK2 mutation carriers, who were either asymptomatic (n = 18) or had a phenotype resembling sporadic PD (n = 8). All patients also underwent PET scans with 18F-6-fluoro-l-dopa (FD), 11C-(±)-α-dihydrotetrabenazine (DTBZ), and 11C-d-threo-methylphenidate (MP) to measure dopaminergic function in the striatum. The levels of CSF markers were then compared to each PET measurement., Results: Reduced CSF Aβ42 and tau levels correlated with lower striatal dopaminergic function as determined by all 3 PET tracers, with a significant association between Aβ42 and FD uptake. When cases were restricted to carriers of the G2019S mutation, the most common LRRK2 variant in our cohort, significant correlations were also observed for tau., Conclusions: The disposition of Aβ and tau is likely important in both LRRK2-related and sporadic PD, even during early phases of the disease. A better understanding of their production, aggregation, and degradation, including changes in their CSF levels, may provide insights into the pathogenesis of PD and the potential utility of these proteins as biomarkers.

Objective: The objective of the study was to induce transdifferentiation of human hepatoma HepG2 cells into pancreatic-like cells without direct genetic intervention., Methods: HepG2 cells were transfected with plasmids for the hepatocyte marker protein green fluorescent protein (albumin-GFP) and the pancreatic cell marker Discosoma spp red fluorescent protein (elastase-DsRed) to create FAE-HepG2 cells. Fluorescent marker expression was used to monitor in vitro transdifferentiation stimulated 100 mM CCl₄, 2 mM D-galactosamine, or 200 μM ZnCl₂. Concentrations were selected for optimal cell survival rate. Transdifferentiation was also characterized by immunohistochemical detection of amylase, glucagon, and insulin and by polymerase change reaction analysis of amylase and insulin mRNA production., Results: Control cells expressed albumin-GFP but no elastase-DsRed. By 30 days of culture, all 3 agents induced expression of pancreatic-like cell marker elastase-DsRed. ZnCl₂ was the most effective as most cells expressed elastase-DsRed in the absence of simultaneous expression of albumin-GFP. For CCl₄ and D-galactosamine, elastase-DsRed was expressed in the same cells as albumin-GFP. Cells treated by each agent also expressed amylase, insulin, and glucagon proteins and mRNAs., Conclusions: Without direct genetic intervention, select low small molecules can induce in vitro transformation of hepatoma cells into pancreatic-like cells.

Study Design: Retrospective multicenter study., Objective: To review the clinical characteristics of traumatic cervical spinal cord injury (SCI) associated with ossification of the posterior longitudinal ligament (OPLL)., Summary of Background Data: Despite its potentially devastating consequences, there is a lack of information about acute cervical SCI complicated by OPLL., Methods: This study included consecutive patients with acute traumatic cervical SCI (Frankel A, B, and C) who were admitted within 48 hours of injury to 34 spine institutions across Japan. For analysis of neurologic outcome, patients who had completed at least a 6-month follow-up were included. Neurologic improvement was defined as at least one grade conversion in Frankel grade., Results: A total of 453 patients were identified (367 men, 86 women; mean age, 59 years). OPLL was found in 106 (23%) patients (87 men, 19 women; mean age, 66 years). Most of the patients with OPLL (94 of 106) were without bone injury, presenting with incomplete SCI. The prevalence of OPLL reached 34% in SCI without bone injury. The cause of SCI was predominantly falls (74%). Only 25% of the patients were aware of OPLL. Half of the OPLL patients reported gait disturbance before injury. Forty-eight (52%) OPLL patients without bone injury underwent surgery (median, 13.5 days after injury), mostly laminoplasty. Overall, no significant difference was noted in neurologic improvement between surgery group and conservative group. However, further stratification showed that surgery was associated with greater neurologic recovery in patients who had gait disturbance before injury (P = 0.04)., Conclusion: Prevalence of OPLL among cervical SCI was alarmingly high, especially in those without bone injury. Most of cervical SCI associated with OPLL were incomplete, without bone injury, and caused predominantly by low-energy trauma. The majority of the patients were unaware of OPLL. Surgery produced better neurologic recovery in patients who had gait disturbance before injury.

Study Design: We categorized the four types of ossification of the posterior longitudinal ligament (OPLL) of the cervical spine into two groups. We biochemically investigated the genetic differences in the osteogenic differentiation potency between the two groups., Objective: To investigate the genetic differences in the osteogenic differentiation potency according to the OPLL classification., Summary of Background Data: Clinical studies on OPLL have revealed that the risk of progression of the ossification area is greatest for continuous and mixed type OPLL. However, until now, these four types of OPLL have been studied as a single condition., Methods: We categorized the four types of OPLL into the OPLL continuous (continuous or mixed type) and OPLL segmental groups (segmental or circumscribed type). Paraspinal ligaments were aseptically obtained from OPLL patients during surgery. The fibroblast-like cells that migrated from the explants were used for experiments. The cells were placed in a 60-mm culture dishes for total ribonucleic acid preparation and 12 well microplates for alkaline phosphatase (ALP) activity staining. After cultures reached confluence, the cells were cultured in osteogenic medium. The messenger ribonucleic acid expression of bone morphogenetic protein-2 (BMP-2), osterix, tumor necrosis factor-α-stimulated gene-6, and ALP was analyzed by quantitative real time-polymerase chain reaction. Osteogenic differentiation of fibroblast-like cells was determined by histochemically detecting ALP production., Results: After osteogenic induction, BMP-2 expression increased in the OPLL continuous and segmental groups. Osterix expression increased in the OPLL continuous group only. Tumor necrosis factor-α-stimulated gene-6 expression was suppressed in the OPLL continuous and segmental groups. ALP expression as well as ALP activity staining was higher in the OPLL continuous group than in the OPLL segmental group. CONCLUSION.: The study revealed genetic differences in the osteogenic differentiation potency between the OPLL continuous and segmental groups. We propose to distinguish OPLL continuous group from segmental group in biochemical studies on OPLL.

One of the radiologic patterns associated with IgG4-related systemic disease was similar to that of pulmonary sarcoidosis. We analyzed whether suspected pulmonary sarcoidosis might include unrecognized IgG4-related systemic disease. The enrolled patients had bilateral hilar lymphadenopathy and/or lung nodules on chest computed tomography, used to diagnose the patients who could either be compatible with or suggested as having pulmonary sarcoidosis. The IgG4 levels were retrospectively measured. Bronchoalveolar lavage (BAL) was analyzed for the presence of IgG subclasses, and specimens were stained by an antibody to IgG4. We compared these data in the suspected sarcoidosis patients, with or without elevated serum IgG4, with the laboratory data and bronchoscopy results in patients with definite sarcoidosis. All enrolled patients were followed for over 5 years. The patients were classified as 49 definite and 44 suspected sarcoidosis patients. Eight patients, including 6 suspected sarcoidosis patients, had elevated abnormal levels of serum IgG4. The suspected sarcoidosis patients had significantly lower percentages of lymphocytes and IgG in the BAL. One suspected sarcoidosis patient had positive IgG4 staining in a lung specimen. The elevated serum IgG4 patients among the patients with suspected sarcoidosis showed significantly higher levels of BAL IgG4, IgG4/IgG, and IgG4/IgG3 compared with the levels of the normal serum IgG4 patients. The follow-up study revealed that 1 patient with elevated serum IgG4 was complicated with other organ failure caused by IgG4-related systemic disease, and Castleman disease was diagnosed in 2 patients. IgG4-related systemic disease was, therefore, identified among the patients with elevated serum IgG4.

Study Design: Retrospective clinical review and prospective report of postoperative delirium after cervical spine surgeries., Objective: To investigate factors contributing to the development of delirium after cervical surgery and see whether amended therapeutic protocols could improve or alter postoperative outcomes., Summary of Background Data: Important consequences of postoperative delirium for the orthopedic patients include impaired recovery and increased morbidity and mortality. Although its risk factors have been reported in orthopedic surgery, there are a very few reports regarding postoperative delirium in spine surgery., Methods: Eighty-one cervical myelopathy patients were retrospectively examined about the incidence of postoperative delirium and the risk factors. Similarly, 41 patients who received postoperative care under modified protocols were prospectively examined., Results: Postoperative delirium occurred more commonly in patients over 70 years and those with hearing impairment. Patients who received high-dose methylprednisolone (>1000 mg) demonstrated an increased incidence of postoperative delirium. Under modified protocol, we reduced the usage of methylprednisolone and encouraged free body movement with cervical orthosis immediately after surgery. The incidence of postoperative delirium was significantly lower under the modified protocol., Conclusion: Early commencement of mobilization after cervical spine surgery would be crucial to the prevention of postoperative delirium in the elderly.

To evaluate the effect of angiotensin II type1 receptor blocker on nerve regeneration delay in diabetic rats, nerve regeneration was monitored by a pinch test on the crushed sciatic nerves of streptozotocin-induced diabetic rats. Nerve regeneration was significantly delayed in diabetic rats and was partly ameliorated by treatment with olmesartan medoxomil (3 mg/kg/day, orally). In the ipsilateral dorsal root ganglia, the mRNA level of insulin-like growth factor-1 and ciliary neurotrophic factor (CNTF) was downregulated, whereas the mRNA level of neurotrophin-3 and CNTF receptor was upregulated. Olmesartan medoxomil significantly enhanced the CNTF expression. These results showed that angiotensin II type1 receptor blocker treatment is effective on nerve regeneration delay in diabetic animals and may provide an effective therapy for clinical diabetic neuropathy.

Summary of Background Data: Ossification of the posterior longitudinal ligament (OPLL) is an ectopic bone formation in the ligament tissue of the spine, causing myelopathy as a result of chronic pressure on the spinal cord and nerve roots. It has been further categorized into 4 types, that is, segmental, continuous, mixed types, and the other types; however, differences in the detail of the progression in the ossification and natural history of the disease among these types have not been clarified., Objective: To find out the systemic feature, which has relevance to the disease state of OPLL., Methods: To characterize these types, we conducted an investigation of cardiovascular factors [blood pressure, blood loss during or after surgery, bleeding time, coagulation factors (prothrombin test, activated partial thromboplastin time)] among OPLL, cervical spondylotic myelopathy (CSM), and subtypes of OPLL (continuous, mixed, segmental, and the other types)., Study Design: Retrospective case series., Results: These parameters of patients with cervical spondylotic myelopathy were used as a control (CSM patients). Although there was no significant difference in bleeding time and coagulation factors, blood loss after surgery of OPLL patients was significantly higher than that of CSM patients (P<0.01). Furthermore, blood loss of patients with continuous type of ossification was significantly higher (P<0.05) than that of patients with segmental type of ossification, which was nearly equal to that of CSM patients. Blood loss of patients with mixed type of ossification showed the value of the middle of segmental and continuous types.

Study Design: A prospective study in 19 patients after cervical laminoplasty, using magnetic resonance imaging., Objective: To evaluate the value of spinal cord shift at 24 hours after cervical laminoplasty., Summary of Background Data: Postoperative C5 palsy is a noticeable complication within 1 week after cervical laminoplasty. The root tethering due to the posterior shift of the spinal cord after laminoplasty was reported as one of the causes of C5 palsy. However, the spinal cord shift after surgery within 1 week is unknown., Methods: The posterior shift of the spinal cord was measured in 19 consecutive patients on magnetic resonance images at 24 hours and 2 weeks after cervical laminoplasty., Results: The mean posterior shift of the spinal cord at 24 hours was 2.8 mm, with the maximum at the C5 level, decreasing to 1.9 mm at 2 weeks. The posterior shift of the spinal cord at C5 was correlated with the amount of the dura mater at C4, C5, and C6 levels. In a patient with right C5 palsy, posterior shift at C5 level was 5.5 mm, decreasing to 3.0 mm at 2 weeks after surgery. The posterior shift of the spinal cord was not correlated with the sagittal alignment., Conclusion: The posterior shift of the spinal cord at 24 hours had a tendency to shift more posteriorly than that observed at 2 weeks after cervical laminoplasty. C5 palsy may be prevented if the expansion of dura mater, which is strongly correlated with the posterior shift, can be controlled.

Study Design: A multicenter cohort study was performed retrospectively., Objective: To identify radiographic predictors for the development of myelopathy in patients with ossification of the posterior longitudinal ligaments (OPLL)., Summary of Background Data: The pathomechanism of myelopathy in the OPLL remains unknown. Some patients with large OPLL have not exhibited myelopathy for a long periods of time. Predicting the course of future neurologic deterioration in asyptomatic patients with OPLL is difficult at their initial visit., Methods: A total of 156 OPLL patients from 16 spine institutes with an average of 10.3 years of follow-up were reviewed. Subjects underwent a plain roentgenogram, computed tomography (CT), and magnetic resonance imaging of the cervical spine during the follow-up. The trauma history of the cervical spine, maximum percentage of spinal canal stenosis in a plain roentgenogram and CT, range of motion of the cervical spine, and axial ossified pattern in magnetic resonance imaging or CT were reviewed in relation to the existence of myelopathy., Results: All 39 patients with greater than 60% spinal canal stenosis on the plain roentgenogram exhibited myelopathy. Of 117 patients with less than 60% spinal canal stenosis, 57 (49%) patients exhibited myelopathy. The range of motion of the cervical spine was significantly larger in patients with myelopathy than in those of without it. The axial ossified pattern could be classified into 2 types: a central type and a lateral deviated type. The incidence of myelopathy in patients with less than 60% spinal canal stenosis was significantly higher in the lateral deviated-type group than in the central-type group. Fifteen patients of 156 subjects developed trauma-induced myelopathy. Of the 15 patients, 13 had mixed-type OPLL and 2 had segmental-type OPLL., Conclusion: Static and dynamic factors were related to the development of myelopathy in OPLL.

Study Design: A sex- and age-matched case-control study with genotyping of the FokI variant of the vitamin D receptor gene (VDR) was carried out., Objectives: To facilitate the early prediction, prevention, and treatment of ossification of the posterior longitudinal ligament (OPLL) of the spine, we analyzed the FokI variant of VDR and past body mass indexes, histories of past illness, family history, and body pliability along with lifestyle factors., Summary of Background Data: Many possible genetic and environmental risk factors for OPLL have been suggested, including male sex, high body mass index, diabetes mellitus, trauma, hormonal imbalance, and dietary and sleeping habits and genetic variants., Methods: Both a self-administered questionnaire and whole blood samples were obtained from 63 patients with OPLL and 126 sex-, age-, and hospital-matched controls free of backbone diseases were randomly selected from hospital patients. VDR genotyping was carried out using PCR-RFLP methods. After univariate analysis, multivariate and subgroup analyses according to the VDR genotype was applied to clarify the confounding relationship between VDR genotype and other possible risk factors., Results: A multivariate analysis revealed that the VDR FF genotype, family history of myocardial infarction, high body mass index at age 40, long working hours, and working with night shift to be independent potent risk factors for OPLL., Conclusion: The risk of developing OPLL may possibly be reduced gradually and effectively by removing or minimizing the effect of such lifestyle factors one at a time through targeted preventive intervention.

Study Design: An anatomic study investigated the attachment of the nuchal muscles to the spinous process., Objective: To investigate the anatomic details of the attachment of the nuchal muscles to the spinous process, and which muscles are spared, and to what extent, when the C7 spinous process is preserved in the cervical laminoplasty., Summary of Background Data: In previous studies, it was reported that the incidence of postoperative axial pain was lower in C3-C6 laminoplasty than in C3-C7 laminoplasty, emphasizing the effectiveness of the former procedure where discission of the nuchal muscles that are attached to the C7 spinous process is avoided. However, there have been no detailed anatomic studies of the attachment of the nuchal muscles to the spinous process at the cervicothoracic junction., Methods: The anatomy of the speculum rhomboideum of the trapezius, rhomboideus minor, rhomboideus major, serratus posterior superior, splenius capitis, and splenius cervicis to the spinous processes of the cervicothoracic junction were studied using 50 cadavers., Results: The possibility of total discission of the speculum rhomboideum of the trapezius was 0% with C3-C6 laminoplasty and 18% with C3-C7 laminoplasty. More than 50% preservation of the speculum rhomboideum of the trapezius is possible in 72% in C3-C6 laminoplasty and 16% in C3-C7 laminoplasty. In C3-C7 laminoplasty, the possibility of partial preservation of the rhomboideus minor, serratus posterior superior, and splenius capitis at the spinous process was 0%, 66%, and 29%, respectively. The rhomboideus major in 16% and the splenius cervicis in 56% could be completely preserved without partial discission of the muscle attachment. On the other hand, in C3-C6 laminoplasty, the muscles that were spared without complete discission of the muscular attachment at the spinous process were the rhomboideus minor in 35%, the serratus posterior superior in 100% and the splenius capitis in 67%. The rhomboideus major in 76% and the splenius cervicis in 80% were completely spared without partial discission of the muscular attachment., Conclusion: The current study confirmed that C3-C6 laminoplasty in which the C7 spinous process is preserved reduces invasion of the nuchal muscles.

Study Design: Retrospective multi-institutional study, Objective: To describe the surgical outcomes in patients with ossification of the posterior longitudinal ligament in the thoracic spine (T-OPLL) and to clarify factors related to the surgical outcomes., Summary of Background Data: Detailed analyses of surgical outcomes of T-OPLL have been difficult because of the rarity of this disease., Methods: The subjects were 154 patients with T-OPLL who were surgically treated at 34 institutions between 1998 and 2002. The surgical procedures were laminectomy in 36, laminoplasty in 51, anterior decompression via anterior approach in 25 and via posterior approach in 29, combined anterior and posterior fusion in 8, and sternum splitting approach in 5 patients. Instrumentation was conducted in 52 patients. Assessments were made on (1) The Japanese Orthopedic Association (JOA) scores (full score, 11 points), its recovery rates, (2) factors related to surgical results, and (3) complications and their consequences., Results: (1) The mean JOA score before surgery was 4.6 +/- 2.0 and, 7.1 +/- 2.5 after surgery. The mean recovery rate was 36.8% +/- 47.4%. (2) The recovery rate was 50% or higher in 72 patients (46.8%). Factors significantly related to this were location of the maximum ossification (T1-T4) (odds ratio, 2.43-4.17) and the use of instrumentation (odds ratio, 3.37). (3) The frequent complications were deterioration of myelopathy immediately after surgery in 18 (11.7%) and dural injury in 34 (22.1%) patients., Conclusion: The factors significantly associated with favorable surgical results were maximum ossification located at the upper thoracic spine and use of instrumentation. T-OPLL at the nonkyphotic upper thoracic spine can be treated by laminoplasty that is relatively a safe surgical procedure for neural elements. The use of instrumentation allows correction of kyphosis or prevention of progression of kyphosis, thereby, enhancing and maintaining decompression effect, and its use should be considered with posterior decompression.

The importance of oxidative stress in hypertension has recently received increasing attention. The association between the incidence of hypertension and a super family of antioxidant enzymes, glutathione S-transferase (GST)A1, GSTM1 and GSTT1, polymorphisms was investigated in 468 Japanese participants in a health screening program. The frequency of the GSTA1*B allele carriers was significantly higher in hypertensive patients than normotensive participants [adjusted odds ratio (OR): 1.8; 95% confidence interval (CI): 1.1-2.9]. The risk of hypertension was significantly increased in the GSTA1*B allele carriers having also the GSTM1 null genotype or both the GSTM1 and GSTT1 null genotypes (adjusted OR: 2.4; 95% CI: 1.2-4.9; adjusted OR: 3.1; 95% CI: 1.0-9.5, respectively). This is the first report identifying the GSTA1*B allele as a genetic risk factor for hypertension. The determination of the GST genotypes may help in identifying individuals at high-risk for hypertension.

Background: Protocols for tight control of blood glucose can be difficult to achieve in the surgical setting, especially when relying upon intermittent blood glucose testing. A continuous blood glucose monitoring system can facilitate blood glucose management. In the present study, we compared blood glucose measured continuously (STG-22, Nikkiso, Tokyo, Japan), during surgery with coincident measurements obtained intermittently using a conventional laboratory glucometer (ABL 800FLEX (Radiometer Medical Aps, [symbol: see text], Denmark). The goal of the study was to determine the reliability and accuracy of the continuous method during surgery., Material and Methods: Twenty-nine patients scheduled for routine surgery with general anesthesia were enrolled in this study. After anesthetic induction, a 20G IV catheter was inserted in a peripheral forearm vein and connected to the continuous blood glucose monitor. A radial arterial catheter was also inserted from which samples for blood glucose estimation were obtained by an anesthesiologist, following an established protocol of discarding 3 mL of blood before the actual blood sampling. Blood glucose was measured by ABL 800FLEX immediately after sampling. One hundred points of paired blood glucose values were obtained, which were compared using Bland and Altman analysis., Results: Bias and upper and lower limits of agreement were -2.6, 23, and -28, respectively. The percentage error of the lower/upper limits of agreement was 21% and 18%, respectively., Discussion and Conclusions: The blood glucose measurements obtained continuously agreed with the coincident intermittent measurements within 21%. The STG-22 may still be useful for following changes continuously and reducing the frequency of intermittent measurement, but the need for testing samples with a reliable device is not eliminated.

Study Design: A radiographic study in 111 patients using radiographs was conducted., Objective: To clarify whether the modified laminoplasty with C3 laminectomy preserving the semispinalis cervicis (SSC) inserted into C2 could maintain the postopertive range of motion (ROM) and sagittal alignment compared with conventional C3-C7 laminoplasty reattaching the muscle to C2., Summary of Background Data: Intraoperative injury of the SSC is relevant to the significant loss of ROM and the malalignment after laminoplasty. To expose the C3 lamina, however, the SSC inserted into C2 could not be preserved in conventional C3-C7 laminoplasty., Methods: The ROM and sagittal alignment of 70 patients (group A) (52 men, 18 women, mean age 59 y, mean follow-up period 1 y and 7 mo) with C4-C7 laminoplasty with C3 laminectomy were compared with those of 41 patients (group B) (28 men, 13 women, mean age 59 y, mean follow-up period 2 y and 6 mo) with C3-C7 laminoplasty using radiographs of the cervical spine., Results: Regarding C2-C7 ROM, the postoperative ROM was larger (P=0.003) and the decrease rate of ROM was smaller (P=0.0006), and decreased ROM in extension was smaller (P<0.0001) in group A. Regarding O-C2 ROM, the increased ROM was smaller (P=0.043) and increased ROM in extension was smaller (P=0.001) in group A. Regarding O-C7 ROM, the postoperative ROM was larger (P=0.029) in group A. Regarding the cervical alignment, the increased lordotic angle at O-C2 was smaller (P=0.046) in group A., Conclusions: This modified laminoplasty preserving the SSC inserted into C2 is an effective procedure for maintaining postoperative ROM, especially in extension, and sagittal alignment of the upper cervical spine well.

Background: In patients with replanted digits, systemic heparinization or other techniques may be used for prevention of thrombosis of the vascular anastomoses or to prevent coagulation at the drainage site (e.g., a fish-mouth incision or partially removed nail). However, systemic heparin may be contraindicated or require cautious administration in certain patients. The authors injected calcium heparin subcutaneously into the congested replanted digits of seven patients with a history of or undergoing treatment for hemorrhoids or gastric ulcer and drained the congestion by means of a fish-mouth incision., Methods: With this method, 0.8 ml (20,000 U) of calcium heparin for subcutaneous injection was diluted with 1.2 ml of saline to prepare a solution containing 1000 U in 0.1 ml; this calcium heparin solution (1000 U) was initially injected into the tip of the congested digit. If required, additional doses of 500 U each were administered every 24 hours until the congestion improved., Results: No worsening of bleeding from hemorrhoids or gastric ulcer was seen after the administration of calcium heparin in these patients. Regarding duration of action, continuous bleeding for approximately 6 hours was obtained after subcutaneous injection of 1000 U, and thereafter, adequate drainage was achieved for approximately 24 hours by stimulating the drainage site., Conclusions: Among patients in whom systemic heparin is contraindicated or who require cautious administration, this is a very effective technique in those in whom congestion fails to improve despite thrombectomy, patients in whom thrombectomy or vascular reanastomosis is not possible, and patients with congestion caused by narrow anastomosed veins.

Introduction: C3-C7 laminoplasty has been the standard treatment for cervical myelopathy, although several recent reports described C3-C6 laminoplasty for preserving the muscles inserting in C7 and reducing postoperative axial symptoms. However, postoperative changes at C6/C7 of the lower end of C3-C6 laminoplasty, especially regarding a possibility of postoperative spinal canal narrowing have not been measured. The purpose of this study was to clarify postoperative changes at the lower end of laminoplasty., Methods: Pre and postoperative spinal dura diameter at the lower end of conventional C3-C7 laminoplasty using MRI, and the related factors for spinal dura diameter and the causes of postoperative dura narrowing were investigated., Results: At the last follow-up after C3-C7 laminoplasty, dura diameter at C7/T1 was significantly wider after operation than before operation, and postoperative narrowing of dura diameter, which was found in 20% of patients, was a maximum amount of one millimeter. No pre and postoperative factor significantly correlated with dura diameter at C7/T1. The causes of postoperative narrowing at the lower end of laminoplasty were disc protrusion and/or posterior scar, or segmental angulation of the spinal cord., Conclusion: In conclusion, the presence of preoperative subarachnoid space over one millimeter at C6/C7 may be able to be one of the radiological indications for C3-C6 laminoplasty.

Purpose: To establish proper contact lens care as a common practice by discovering the quantity and condition of protein deposition on various types of soft contact lenses., Methods: The amounts of deposition of two proteins found in tear fluid, lysozyme and albumin, on various types of contact lenses were measured. Lenses deposited with albumin and lenses deposited with lysozyme were stained with Coomassie brilliant blue (CBB). Frozen cross-sections of these lenses were examined using a microscope., Results: A considerably larger amount of lysozyme was found on group IV (U.S. Food and Drug Administration classification) contact lenses. Conversely, there were no significant differences between the four groups in the quantity of albumin found. When various lenses were stained with CBB, only the lysozyme-deposited lenses of group IV obtained a strong tint. When cross-sections of the tinted group IV contact lenses were examined, not only the surface, but also the matrix of the lens was stained., Conclusions: Results suggested that the reason group IV lenses accumulated a considerably greater amount of lysozyme than did lenses of other groups is that lysozyme accumulates not only on the surface, but also in the matrix of group IV lenses.

Background: We proposed a novel therapeutic strategy against central baroreflex failure: implementation of an artificial baroreflex system to automatically regulate sympathetic vasomotor tone, ie, a bionic baroreflex system (BBS), and we tested its efficacy in a model of sudden hypotension during surgery., Methods and Results: The BBS consisted of a computer-controlled negative-feedback circuit that sensed arterial pressure (AP) and automatically computed the frequency (STM) of a pulse train required to stimulate sympathetic nerves via an epidural catheter placed at the level of the lower thoracic spinal cord. An operation rule was subsequently designed for the BBS using a feedback correction with proportional and integral gain factors. The transfer function from STM to AP was identified by a white noise system identification method in 12 sevoflurane-anesthetized patients undergoing orthopedic surgery involving the cervical vertebrae, and the feedback correction factors were determined with a numerical simulation to enable the BBS to quickly and stably attenuate an external disturbance on AP. The performance of the designed BBS was then examined in a model of orthostatic hypotension during knee joint surgery (n=21). Without the implementation of the BBS, a sudden deflation of a thigh tourniquet resulted in a 17+/-3 mm Hg decrease in AP within 10 seconds and a 25+/-2 mm Hg decrease in AP within 50 seconds. By contrast, during real-time execution of the BBS, the decrease in AP was 9+/-2 mm Hg at 10 seconds and 1+/-2 mm Hg at 50 seconds after the deflation., Conclusions: These results suggest the feasibility of a BBS approach for central baroreflex failure.

Study Design: Results of C4-C7 laminoplasty with C3 laminectomy and C3-C7 laminoplasty were compared., Objectives: To clarify prospectively whether the modified laminoplasty preserving the semispinalis cervicis inserted into C2 could reduce the axial symptoms compared with conventional laminoplasty reattaching the muscle to C2., Summary of Background Data: Intraoperative damage of the semispinalis cervicis is relevant to the development of axial symptoms after laminoplasty. In C3-C7 laminoplasty, however, it is difficult to preserve the muscle insertion into C2 while opening the C3 lamina., Methods: The axial symptoms of 40 patients (Group A) with C4-C7 laminoplasty with C3 laminectomy were compared with those of 16 patients (Group B) with C3-C7 laminoplasty. The cross-sectional areas of the cervical posterior muscles were measured on magnetic resonance images., Results: The number of patients with no postoperative axial symptoms increased (P = 0.035) from 19% to 52.5%, and the number of patients whose symptoms worsened after surgery decreased (P = 0.020) from 50% to 17.5%. The average atrophy rate of cross-sectional area was smaller (P < 0.001) in Group A (2.4%) than in Group B (10.8%)., Conclusions: This method was less invasive to the cervical posterior muscles than C3-C7 laminoplasty. This is an effective procedure for preventing postoperative axial symptoms.

Background: Recent clinical trials have demonstrated that aggressive lipid lowering by statins could prevent recurrent events after acute coronary syndrome (ACS). We hypothesized that this efficacy was caused by a significant reduction in plaque volume by aggressive LDL cholesterol (LCL-C) lowering. The present study investigated the effect of early statin treatment on plaque volume of a nonculprit lesion by serial volumetric intravascular ultrasound in patients with ACS., Methods and Results: Seventy patients with ACS were enrolled. All patients underwent emergency coronary angiography and percutaneous coronary intervention (PCI). They were randomized to intensive lipid-lowering therapy (n=35; atorvastatin 20 mg/d) or control (n=35) groups after PCI. Volumetric intravascular ultrasound analyses were performed at baseline and 6-month follow-up for a non-PCI site in 48 patients (atorvastatin, n=24; control, n=24). LDL-C level was significantly decreased by 41.7% in the atorvastatin group compared with the control group, in which LDL-C was increased by 0.7% (P<0.0001). Plaque volume was significantly reduced in the atorvastatin group (13.1+/-12.8% decrease) compared with the control group (8.7+/-14.9% increase; P<0.0001). Percent change in plaque volume showed a significant positive correlation with follow-up LDL-C level (R=0.456, P=0.0011) and percent LDL-C reduction (R=0.612, P<0.0001), even in patients with baseline LDL-C <125 mg/dL., Conclusions: Early aggressive lipid-lowering therapy by atorvastatin for 6 months significantly reduced the plaque volume in patients with ACS. Percent change in plaque volume showed a significant positive correlation with percent LDL-C reduction, even in patients with low baseline LDL-C.

To clarify the characteristics of injuries of motorcyclists dying in accidents in relation to helmet type, we retrospectively analyzed forensic autopsies of 36 helmeted motorcycle riders. The presence of major injuries and injury severity were evaluated with the injury severity score and the 1990 revision of the Abbreviated Injury Scale. Persons with open-face helmets (19 cases) were significantly more likely to have sustained severe head and neck injuries, especially brain contusions, than were persons with full-face helmets (17 cases). Furthermore, major injuries of the chest or abdomen, rib fractures, lung injuries, and liver injuries were each present in more than one quarter of all cases (26.3% to 70.6%), but their prevalences did not differ significantly between riders with different types of helmet. Because many types of head and neck injuries cannot be prevented and fatal chest and abdominal injuries occur despite the use of full-face helmets, more effective helmets and devices for protecting the chest and abdomen are needed to decrease deaths from motorcycle accidents.

Study Design: A sex- and age-matched case-control study was carried out., Objectives: To facilitate early prediction, prevention, and treatment of ossification of the posterior longitudinal ligament of the spine, the authors analyzed histories of past illness, past body mass indexes, and body pliableness by nature, adjusted for other factors considered to be risk factors., Summary of Background Data: The cause of ossification of the posterior longitudinal ligament of the spine has not yet been elucidated in detail, although many possible causative factors have been suggested, including gender, diabetes mellitus, trauma, hormonal imbalance, and dietary habits., Methods: A self-administered questionnaire was obtained from 69 patients with ossification of the posterior longitudinal ligament of the spine and 138 sex- and age-matched control participants who were free of spinal disease, randomly selected from participants in a health checkup in a town. After univariate analysis, a stepwise method was applied to select significant factors in multivariate analysis., Results: A multivariate analysis revealed that the following three indicators were independent potent risk factors for ossification of the posterior longitudinal ligament of the spine: history of diabetes mellitus, history of lumbago, and maximum body mass index before manifestation > or =25, after adjustment for other possible lifestyle risk factors., Conclusion: Excessive weight gain between 20 and 40 years of age, diabetes mellitus, and lumbago were found to be independent risk factors for ossification of the posterior longitudinal ligament of the spine. Follow-up studies, including the addition of hospital-based control participants and analysis of genetic polymorphisms, will be needed in the future.

To date, the events that mediate tumor progression in pancreatic cancer are still poorly understood. Cytogenetic, allelotype, and somatic cell hybrid studies in human pancreatic adenocarcinoma have suggested that chromosome 18 may carry tumor suppressor genes (TSGs), including SMAD4. We previously identified that LOH of 18q at the SMAD4 locus, along with LOHs on 17p and 12q, positively associated with poor prognoses of pancreatic cancer patients. However, restoration of the SMAD4 gene did not suppress in vitro proliferation of pancreatic cancer cells that harbored homozygous deletion of this gene. An intraductal papillary mucinous neoplasm (IPMN ) is thought to be one of the premalignant lesions of the pancreas that progresses to carcinoma. Although there were frequent LOH (7/14, 50%) at the SMAD4 locus in IPMN samples, SMAD4 protein was observed immunohistochemically in tumor cells, and no mutations of the SMAD4 gene were observed, suggesting that it is the existence of a TSG in 18q, other than SMAD4, that suppresses cell growth. To functionally assess the activity of chromosome 18 in pancreatic cancer, we transferred a normal copy of the chromosome into pancreatic ductal carcinoma cells with and without completely inactivated SMAD4. In this study, in vitro growth of the hybrid cells was significantly suppressed compared with the parental cells, regardless of the initial SMAD4 status. To estimate the metastatic ability of the hybrids, we used a lung colonization model. At the end of the experiment, there was significant suppression of the number of surface metastases developing in mice injected with hybrids in comparison with those injected with parental cells. To identify and characterize genes that are involved in the progression of pancreatic cancer, we used micro-array expression analysis employing a 20k oligo-array system. It was revealed that there was increased expression of 4 genes relating to apoptosis in the 18 chromosome hybrids cells compared with the parental cells. We are now analyzing the function of these genes.

Background: Pitavastatin (NK-104) is a novel inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme for cholesterol biosynthesis. In clinical trials, pitavastatin has been shown to significantly decrease serum LDL cholesterol and triglyceride levels and increase HDL cholesterol. Scavenger receptor-mediated accumulation of oxidized LDL (OxLDL)-derived cholesteryl ester is considered to be a critical step in the development of atherosclerotic foam cell formation. We studied the effect of pitavastatin on CD36 (a class B scavenger receptor) expression by murine macrophages., Methods and Results: Treatment of J774 cells and murine peritoneal macrophages with pitavastatin decreased CD36 mRNA expression in a dose-dependent manner. Decreased CD36 mRNA was associated with decreased CD36 cell surface protein expression in human THP-1 cells and human monocyte-derived macrophages. Pitavastatin also reduced the increase in CD36 mRNA, cell surface protein, and binding/uptake of OxLDL induced by peroxisome proliferator-activated receptor-gamma (PPARgamma) ligands and/or OxLDL. Pitavastatin did not alter the half-life of CD36 mRNA, which suggests pitavastatin downregulates CD36 expression by reducing CD36 transcription. In addition, pitavastatin significantly decreased PPARgamma mRNA and protein expression. Finally, pitavastatin increased p44/42 mitogen-activated protein kinase activity and PPARgamma phosphorylation and increased the ratio of phosphorylated PPARgamma to nonphosphorylated PPARgamma., Conclusions: The present data demonstrate that pitavastatin prevents OxLDL uptake by macrophages through PPARgamma-dependent inhibition of CD36 expression and suggest that pitavastatin could modulate CD36-mediated atherosclerotic foam cell formation.