Controlling joint instability after anterior cruciate ligament transection inhibits transforming growth factor-beta-mediated osteophyte formation.

OBJECTIVE: Abnormal joint instability contributes to cartilage damage and osteophyte formation. We investigated whether controlling joint instability inhibited chronic synovial membrane inflammation and delayed osteophyte formation and examined the role of transforming growth factor-beta (TGF-ß) signaling in the associated mechanism. DESIGN: Rats (n = 94) underwent anterior cruciate ligament (ACL) transection. Anterior tibial instability was either controlled (CAM group) or allowed to continue (SHAM group). At 2, 4, and 8 weeks after surgery, radiologic, histopathologic, immunohistochemical, immunofluorescent, and enzyme-linked immunosorbent assay examinations were performed to evaluate osteophyte formation and TGF-ß signaling. RESULTS: Joint instability increased cartilage degeneration score and osteophyte formation, and cell hyperplasia and proliferation and synovial thickening were observed in the synovial membrane. Major findings were increased TGF-ß expression and Smad2/3 following TGF-ß phosphorylation in synovial membarene, articular cartilage, and the posterior tibial growth plate (TGF-ß expression using ELISA: 4 weeks; P = 0.009, 95% CI [260.1-1340.0]) (p-Smad2/3 expression density: 4 weeks; P = 0.024, 95% CI [1.67-18.27], 8 weeks; P = 0.034, 95% CI [1.25-25.34]). However, bone morphogenetic protein (BMP)-2 and Smad1/5/8 levels were not difference between the SHAM model and the CAM model. CONCLUSIONS: This study showed that the difference between anterior tibial instability caused a change in the expression level of TGF in the posterior tibia and synovial membrane, and the reaction might be consequently involved in osteophyte formation.

Laparoendoscopic Single-site Plus 1-port Donor Nephrectomy: Division of Roles to Shorten Warm Ischemic Time.

BACKGROUND: In this study we present our new surgical procedure, laparoendoscopic single-site surgery plus 1 for donor nephrectomy (LESS+1-DN), which shortens warm ischemic time (WIT) and improves surgical outcomes. METHODS: From January 2013 to February 2017, 15 patients who underwent LESS-DN and 41 patients who underwent LESS+1-DN at our institution were evaluated retrospectively. Patients were divided into 3 groups: group A, 15 cases of LESS-DN; group B, the first 15 patients who underwent LESS+1-DN; and group C, 26 patients who underwent subsequent LESS+1-DN. To reduce WIT, we clearly defined the roles of the surgeon and first assistant in the 26 subsequent LESS+1-DN cases. The surgeon dissected the renal pedicle and harvested the kidney graft using a recovery bag and the first assistant held the recovery bag. RESULTS: The mean operative time in group C (213.7 minutes) was significantly shorter than that in groups A (253.3 minutes) and B (253.8 minutes). The WIT in group C (195.2 seconds) was significantly shorter than that in groups A (389.8 seconds) and B (313.2 seconds). Open conversion was required in 1 case in group A. None of the donors required conversion to open surgery and no perioperative complications occurred in groups B and C. Linear regression analysis of the LESS+1-DN operative times and consecutive case numbers demonstrated a shallow learning curve (R2 = 0.392, P < .05). CONCLUSION: Our new procedure that divides the roles of the operator and the first assistant contributed significantly to a shortening of WIT. Dividing roles can facilitate a safer laparoscopic donor nephrectomy.

Chronic active Epstein-Barr virus infection mimicking autoimmune hepatitis exacerbation in a patient with systemic lupus erythematosus.

Chronic active Epstein-Barr virus infection (CAEBV) is characterized by chronic infectious mononucleosis-like symptoms. We report a very rare case with autoimmune hepatitis (AIH) complicated by CAEBV. A 50-year-old woman with systemic lupus erythematosus (SLE) complicated by AIH began to suffer from acute respiratory failure and her clinical symptoms improved rapidly in response to steroid treatment. However, during the gradual tapering of the steroid dose, a steady increase of the serum hepatobiliary enzyme levels subsequently was observed and the patient began to have continuous fever. Moreover, upper gastrointestinal endoscopy revealed multiple intractable gastric ulcers. When EBER-ISH was performed on liver biopsy and gastric mucosal biopsy specimens, EBER-positive lymphocytes were observed. When peripheral blood was examined, 2.1 × 10(6) copies/µg of EBV-DNA were observed in the CD4-positive T cells, confirming the diagnosis of CAEBV. A cooling therapy was started by steroid and cyclosporine. Thereafter, despite the start of CHOP therapy, she developed a malignant lymphoma (PTCL-NOS) and died of hepatic failure. When treatment-resistant AIH patients are encountered, not only AIH exacerbation but also CAEBV should be considered in the differential diagnosis.

Effect of surface treatments on the bond strengths of facing composite resins to zirconia copings.

The present study evaluated and compared the bond strength between zirconia and facing composite resin using different surface conditioning methods before and after thermocycling. Four primers, three opaque resins, and two facing composite resins were used, and 10 surface treatment procedures were conducted. The bond strength was measured before and after 4,000 cycles of thermocycling. The mean values of each group were statistically analyzed using one-way analysis of variance (ANOVA). The bond strengths of facing composite resins to zirconia after various treatments varied depending on the primers, opaque resins, body resins, and thermocycling. The application of primers and opaque resins to the zirconia surface after sandblasting is expected to yield strong bond strength of the facing composite resin (Estenia CG&B) even after thermocycling.

Control of individual phase relationship between coupled oscillators using multilinear feedback.

Due to various technological and medical demands, several methods for controlling the dynamical behavior of coupled oscillators have been developed. In the present study, we develop a method to control the individual phase relationship between coupled oscillators, in which multilinear feedback is used to modify the interaction between the oscillators. By carrying out a simulation, we show that the phase relationship can be well controlled by using the proposed method and the control is particularly robust when the target coupling function is selected properly.

Retention of zirconia copings on zirconia implant abutments cemented with provisional luting agents.

The purpose of this study is to measure and compare the retentive force of zirconia-based all-ceramic crowns cemented on zirconia abutments using five provisional luting agents. In addition, the effect of sandblasting and thermocycling on the retentive force was evaluated. Two hundred zirconia abutments and copings were fabricated (Procera system; Nobel Biocare) and divided into five groups. Hy bond temporary cement hard (Hard), Hy bond temporary cement soft (Soft), experimental temporary cement (New), Tempbond NE (Temp) and Freegenool temporary pack (Pack) were used according to the manufacturers' instructions. Each group was divided into two groups, one with and one without sandblasting. Furthermore, thermocycling up to 2000 cycles was conducted on half of each group. After 24 h and thermocycling, the retentive force was measured using a universal testing machine. The data were subjected to analysis of variance, and comparisons of the means were performed with a Games-Howell test at a level of 95%. As a result, Hard showed the highest retentive force, sandblasting was effective for improving the durability, and no effect of sandblasting was detected in the others. New showed stability of the retentive force even after thermocycling. The retentive force of Temp and Pack decreased significantly after thermocycling even with sandblasting. The retentive forces were different from the provisional cement and sandblasting, and Temp and Pack may not be appropriate for the retention of single-tooth zirconia abutments and coping restorations.

Modeling of a density oscillator.

A density oscillator is a well-known system, which exhibits relaxation oscillation. It alternately exhibits up and down flows through a pipe that connects two containers filled with fluids that have different densities. Although the up-flow, down-flow, and flow-reversal processes have been studied separately, the entire oscillatory dynamics has not been modeled quantitatively. In this study, we derive a model of a density oscillator by considering all the above mentioned processes. The model thus obtained describes the oscillatory behavior in a unified manner, and its viscosity and pipe-length dependence is well described. Moreover, for the demonstration of this model, we have extended it to describe the dynamical behaviors observed in coupled density oscillators. Thus, this model provides a general expression for density oscillators.

Method to control the coupling function using multilinear feedback.

Methods to control the dynamics of coupled oscillators have been developed owing to various medical and technological demands. In this study, we develop a method to control coupled oscillators in which the coupling function expressed in a phase model is regulated by the multilinear feedback. The present method has wide applicability because we do not need to measure an individual output from each oscillator, but only measure the sum of the outputs from all the oscillators. Moreover, it allows us to easily control the coupling function up to higher harmonics. The validity of the present method is confirmed through a simulation.

Evaluation of plasma C-terminal atrial natriuretic peptide in healthy cats and cats with heart disease.

BACKGROUND: The clinical implications of evaluating C-terminal atrial natriuretic peptide (ANP) concentration in cats are still controversial. HYPOTHESIS: The objective of this study was to investigate the relationship between plasma C-terminal ANP concentration and left atrial pressure (LAP) in healthy cats with volume overload (study 1), and to compare plasma C-terminal ANP in normal cats and cats with cardiomyopathy (study 2). ANIMALS: Five healthy adult cats were used in study 1, and clinically healthy cats (n=8) and cats with cardiomyopathy (n=14) were used in study 2. METHODS: In study 1, cats were anesthetized and given acetated Ringer's solution (100 mL/kg/h for 60 minute) via the cephalic vein. Hemodynamic measurements and blood samples, collected from the jugular vein, were performed at 10-min intervals. In study 2, blood samples from normal cats and cats with cardiomyopathy were collected from the cephalic vein. The plasma C-terminal ANP concentration was determined by radioimmunoassay for human alpha-ANP. RESULTS: In study 1, volume overload significantly increased the C-terminal ANP concentration and LAP from baseline. The C-terminal ANP concentration was strongly correlated with the mean LAP. In study 2, age, E wave velocity, and the ratios of the left atrium to aorta were significantly higher in the cats with cardiomyopathy compared with the normal cats. The C-terminal ANP concentration was significantly higher in the cats with cardiomyopathy compared with the normal cats. CONCLUSIONS AND CLINICAL IMPORTANCE: Our results suggest that the measurement of plasma C-terminal ANP in cats may provide additional information for the diagnosis of heart disease.

Viscosity-dependent flow reversal in a density oscillator.

The density oscillator is a simple system that exhibits self-sustained oscillation. It alternately exhibits up and down flow through a pipe which connects two containers filled with fluids of different densities. However, the mechanism of the flow reversal has not yet been fully understood. From the detailed measurements, we have found that flow reversal begins with an intrusion of fluid, which is followed by rapid growth. This process is definitely sensitive to the viscosities of the fluids, and as a consequence, the critical heights leading to flow reversal are clearly viscosity dependent. These experimental results are explained by a simple model, derived by considering forces acting on a unit volume element located at the tip of the intrusion. Using this model, we can successfully explain the mechanism of flow reversal, which is the most essential process in a density oscillator.

Combination Therapy Using tPA and Edaravone Improves the Neurotoxic Effect of tPA.

SUMMARY: In acute ischemic stroke patients, administration of tissue plasminogen activator (tPA) was proven to improve clinical outcome. On the other hand, neurotoxic effects of tPA have been reported in animal experimental studies. Using a rat thromboembolic stroke model, we examined whether or not the free radical scavenger, edaravone, could attenuate such neurotoxic effect of tPA administered for the purpose of fibrinolysis. Even when early recanalization was induced by administering tPA at 30 minutes after the onset of ischemia, significant amount of tPA was extravasated through the cerebral vessels. Edaravone significantly attenuated extravasation of tPA. Combination therapy using tPA and edaravone appears to be a promising strategy for diminishing the negative effects of tPA.

Cerebral blood oxygenation changes induced by bypass blood flow in moyamoya disease and non-moyamoya cerebral ischaemic disease.

BACKGROUND: Superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis has been used to prevent stroke in patients with moyamoya disease (MD) and non-moyamoya ischaemic disease (non-MD). However, little is yet known regarding the difference between these groups of patients in the extent to which the bypass contributes to maintaining adequate cerebral blood oxygenation (CBO), or the temporal changes after surgery. In the present study, we evaluated the CBO changes induced by bypass blood flow in patients with MD and non-MD during the peri-operative periods employing optical spectroscopy. METHODS: We investigated 13 patients who underwent STA-MCA anastomosis, including 5 MD and 8 non-MD patients. We evaluated the effects of STA blood flow on the CBO in the MCA territory on the anastomosis side, employing visual light spectroscopy during surgery and near infrared spectroscopy (NIRS) at one week after surgery. FINDINGS: In 4 MD patients and one non-MD patient, the STA blood flow increased the oxyhaemoglobin and cortical oxygen saturation (CoSO2), indicating that the bypass supplied blood flow to the ischaemic brain; the CBO changes were observed more frequently in MD than in non-MD patients (p<0.02). The pre-anastomosis CoSO2 (65.4+/-5.4%) in MD was significantly lower than that (72.8+/-7.6%) in non-MD (p<0.05). Postoperative NIRS demonstrated that the bypass began to supply blood flow to the brain in 5 non-MD patients whose bypass did not supply blood flow during surgery. CONCLUSIONS: Although MD has vessels of small diameter as compared to non-MD, the bypass begins to supply blood flow to the ischaemic brain earlier in MD than in non-MD after anastomosis. The fact that the CoSO2 in MD was lower than that in non-MD suggested that the perfusion pressure in MD was lower than that in non-MD, and this might account for the difference in the bypass blood supply after anastomosis between MD and non-MD. Our data suggest that, even if the bypass does not supply blood to the brain during surgery in non-MD, the bypass blood flow gradually increases after surgery.

Feed-forward control of post-stroke movement disorders by on-demand type stimulation of the thalamus and motor cortex.

Deep brain stimulation (DBS) of the thalamus (Vo/Vim) has become popular as a means of controlling involuntary movements, including post-stroke movement disorders. We have also found that post-stroke movement disorders and motor weakness can sometimes be controlled by motor cortex stimulation (MCS). In some forms of movement disorders, motor dysfunction becomes evident only when patients intend to move their body. We have developed an on-demand type stimulation system which triggers stimulation by detecting intrinsic signals of intention to move. Such a system represents feed-forward control (FFC) of involuntary movements. We report here our experience of DBS and MCS for controlling post-stroke movement disorders, and discuss the value of FFC. Excellent control of post-stroke movement disorders was achieved by conventional DBS and/or MCS in 20 of 28 patients with hemichoreoathetosis, hemiballism tremor, and motor weakness. FFC was tested in 6 patients who demonstrated excellent control of post-stroke postural tremor or motor weakness by conventional DBS or MCS. The on-demand stimulation provided satisfactory FFC in 4 of 4 patients with postural tremor and 2 of 2 patients with motor weakness, when the activity of muscles involved in posturing or intention to move was fed into the system. These findings justify further clinical studies on DBS and MCS in patients with post-stroke movement disorders. The on-demand type stimulation system may also be useful for overcoming various post-stroke movement disorders.

Pallidal high-frequency deep brain stimulation for camptocormia: an experience of three cases.

INTRODUCTION: The term "camptocormia" describes a forward-flexed posture. It is a condition characterized by severe frontal flexion of the trunk. Recently, camptocormia has been regarded as a form of abdominal segmental dystonia. Deep brain stimulation (DBS) is a promising therapeutic approach to various types of movement disorders. The authors report the neurological effects of DBS to the bilateral globus pallidum (GPi) in three cases of disabling camptocormia. METHODS: Of the 36 patients with dystonia, three had symptoms similar to that of camptocormia, and all of these patients underwent GPi-DBS. The site of DBS electrode placement was verified by magnetic resonance imaging (MRI). The Burke Fahn and Marsden dystonia rating scale (BFMDRS) was employed to evaluate the severity of dystonic symptoms preoperatively and postoperatively. RESULTS: Significant functional improvement following GPi-DBS was noted in the majority of dystonia cases. At a follow-up observation after more than six months, the overall improvement rate was 71.2 +/- 27.0%, in all dystonia cases who underwent the GPi-DBS. In contrast, the improvement rate of the three camptocormia cases was 92.2 +/- 5.3%. It was confirmed that the improvement rate for camptocormia was much higher than for other types of dystonia. CONCLUSION: According to our experience, a patient with a forward-bent dystonic posture indicative of camptocormia is a good candidate for GPi-DBS. The findings of this study add further support to GPi-DBS as an effective treatment for dystonia, and provide the information on predictors of a good outcome.

Detection of boundaries of subthalamic nucleus by multiple-cell spike density analysis in deep brain stimulation for Parkinson's disease.

When microelectrode recording of single cell activity is employed for targeting the subthalamic nucleus (STN), multiple sampling of single cells is needed to determine whether the electrode has passed through the ventral boundaries of the STN. In contrast, stepwise recording of multiple cell activities by a semimicroelectrode reveals robust changes in such activities at the dorsal and ventral boundaries. We attempted to quantify changes in multiple cell activities by computing multiple-cell spike density (MSD). We analyzed MSD in 60 sides of 30 patients with Parkinson's disease. Neural noise level was defined as the lowest cut-off level at which neural noise is separated from larger amplitude spikes. MSD was analyzed at cut-off levels ranging from 1.2 to 2.0-fold the neural noise level in the white matter in each trajectory. Both the dorsal and ventral boundaries were clearly identified by an increase and a decrease (p < 0.0001) in MSD, respectively, in all the 60 sides. The cut-off level of 1.2-fold showed the clearest change in MSD between the STN and the pars reticulata of substantia nigra. MSD analysis by semimicroelectrode recording represents the most practical means of identifying the boundaries of STN.

A retrospective study of the fluctuation in serum levels of anti-cyclic citrullinated peptide antibody in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the fluctuation in serum levels of anti-cyclic citrullinated peptide antibody (anti-CCP) retrospectively in patients with rheumatoid arthritis (RA). METHODS: Serum levels of anti-CCP were measured retrospectively in 131 patients with RA and 90 patients with non-RA rheumatic diseases using a commercially available kit. All sera were collected from patients during the 22-year period, 1982-2004. To analyze the fluctuation in anti-CCP levels, 17 RA patients were selected on the basis of showing a significantly higher anti-CCP level in a serum sample taken at the first visit (> 80 U/ml), and availability of preserved serum samples that had been taken from each patient at 10 time points. RESULTS: The test gave a sensitivity of 88% (115/131) and a specificity of 81% (73/90). The longitudinal study of 17 RA patients showed that anti-CCP levels were elevated at the first visit in 12 (71%) patients and then decreased gradually, whereas those in the other five (29%) patients fluctuated substantially. In both cases, anti-CCP levels tended to fluctuate in parallel with the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level, reflecting the spontaneous aggravation of arthritis and the efficacy of anti-rheumatic drugs. The courses of three representative RA patients are illustrated in detail along with their therapeutic regimens, and these further confirm the correlation of anti-CCP levels with laboratory parameters (ESR and CRP) as well as the activity of arthritis. CONCLUSION: Measurement of serum anti-CCP levels was found to be useful for not only the diagnosis but also the management of RA.

Relationship between intraoperative transoesophageal echocardiography findings and perfusion lung scintigraphy results on first postoperative day.

BACKGROUND: Although intraoperative transoesophageal echocardiography (TOE) has been used to detect the occurrence of echogenic macro- and/or microembolic phenomena during total hip arthroplasty (THA), no direct correlation between macroembolism and the formation of pulmonary embolism (PE) has been conclusively determined in early postoperative periods after THA. METHODS: Sixty-two patients scheduled for primary THA were enrolled in this study. Intraoperative TOE images were continuously recorded on videotape and the echogenic events were evaluated throughout surgery. Perfusion lung scintigraphy was performed on the first postoperative day (POD1). RESULTS: Perfusion lung scintigraphy revealed the existence of PE in nine (15%) of the 62 patients who underwent THA: five (25%) of 20 patients with cemented THA and four (10%) of 42 patients with non-cemented THA. The grading score of intraoperative TOE findings, including the amount of echogenic particles in right atrium, the longest time of echogenesis and the diameter of the largest echogenic particles, did not differ between the groups with and without PE. The sensitivity, specificity, and positive and negative predictive values for the detection of echogenic macroemboli for the prediction of the development of PE on POD1 were 0.78, 0.60, 0.25 and 0.94, respectively. CONCLUSION: Intraoperative TOE monitoring did not predict the occurrence of PE on POD1.

Periodic oscillatory activity in parahippocampal slices maintained in vitro.

Brain slices maintained in vitro have been extensively used for studying neuronal synchronization. However, the validity of this approach may be questioned since pharmacological procedures are usually required to elicit spontaneous events similar to the EEG activity recorded in vivo. Here, we report that when superfused with control medium, rat brain slices comprising the entorhinal and perirhinal cortices along with a portion of the basolateral/lateral nuclei of the amygdala can synchronously generate periodic oscillatory activity at 5-11 Hz every 5-30 s. The periodic events: (i) correspond intracellularly to synaptic depolarizations in regularly firing neurons analyzed in the three areas; (ii) have no fixed site of onset; (iii) spread with time lags of 8-20 ms; and (iv) continue to occur asynchronously after their surgical isolation. NMDA receptor antagonism reduced the duration of the oscillatory events, while glutamatergic non-NMDA receptor antagonism abolished them. Activation of mu-opioid receptors, a procedure that hyperpolarizes interneurons thus decreasing GABA release, reversibly decreased the rate of occurrence of periodic oscillatory activity (POA). However, periodic events continued to occur during application of GABA(A) or GABA(B) receptor antagonists as well as in the presence of the cholinergic agent carbachol. We also found that POA was abolished by baclofen and irreversibly reduced by the gap junction decoupler carbenoxolone. These findings demonstrate that parahippocampal networks in a brain slice preparation can generate periodic, synchronous activity under quasi-physiological conditions. These network oscillations (i) reflect the activation of ionotropic glutamatergic and GABAergic receptors, (ii) are contributed by gap-junction interactions, and (iii) are controlled by GABA(B) receptors that are presumably located presynaptically.

Infiltration of tissue plasminogen activator through cerebral vessels: evaluation using a rat thromboembolic stroke model.

In recent years, evidence has been accumulating that tissue plasminogen activator (tPA) possesses neurotoxic effects. However, such deleterious effects have been attributed to endogenously generated tPA. In the present study, focusing on exogenously administered tPA for the purpose of fibrinolysis, we evaluated the extent and the degree of extravasated tPA in a rat model of thromboembolic stroke. Even after early recanalization of occluded cerebral vessels, significant infiltration of tPA occurred through the cerebral vessels. It is assumed that exogenous tPA also exerts neurotoxic effects in the ischemic brain tissue.