Voluntary ambulation using voluntary upper limb muscle activity and Hybrid Assistive Limb® (HAL®) in a patient with complete paraplegia due to chronic spinal cord injury: A case report

Context: We sought to describe our experience with the Hybrid Assistive Limb® (HAL®) for active knee extension and voluntary ambulation with remaining muscle activity in a patient with complete paraplegia after spinal cord injury.

Findings: A 30-year-old man with complete paraplegia used the HAL® for 1 month (10 sessions) using his remaining muscle activity, including hip flexor and upper limb activity. Electromyography was used to evaluate muscle activity of the gluteus maximus, tensor fascia lata, quadriceps femoris, and hamstring muscles in synchronization with the Vicon motion capture system. A HAL® session included a knee extension session with the hip flexor and voluntary gait with upper limb activity. After using the HAL® for one month, the patient’s manual muscle hip flexor scores improved from 1/5 to 2/5 for the right and from 2/5 to 3/5 for the left knee, and from 0/5 to 1/5 for the extension of both knees.

Conclusion/clinical relevance: Knee extension sessions with HAL®, and hip flexor and upper-limb-triggered HAL® ambulation seem a safe and feasible option in a patient with complete paraplegia due to spinal cord injury.     

Diastolic mitral annular motion in normal subjects and patients with coronary artery disease

The purpose of this study was to evaluate the characteristicsof mitral annular motion during diastole in 28 normal subjects,40 patients with prior myocardial infarction (MI), and 23 patientswith coronary artery disease but without prior MI. Mitral annularmotion during diastole was obtained from the apex by M-modeechocardiography at the posterior wall of the left ventricle.Determinants of mitral annular excursion during early (MAE-E)and late diastole (MAE-L) were investigated in all subjects.Differences in the MAE-E, MAE-L, and the MAE-L.MAE-E ratio werecompared among the three patient groups. The Doppler-derivedtransmitral flow velocity-time integral during early (El) andlate (AI) diastole and mitral annular excursions during diastolewere obtained in 55 other patients with a prior MI and in 29healthy volunteers. The relationships between the MAE-L: MAE-Eratio and AI: EI ratio in these two groups were studied. The MAE-E was determined mainly by heart rate and left ventricularejection fraction (LVEF). The MAE-L was determined only by age.The magnitude of MAE-E was significantly less in patients witha prior MI than in normal subjects (P<0.01). However, theMAE-L did not differ among the three groups. The MAE-L.MAE-Ewas higher in patients with a prior MI than in normal subjects(P<0.05), and was significantly correlated with AI: EI inhealthy volunteers (r=0.65, P<0.001) and in patients witha prior MI (r=0.50, P<0.001). The MAE-E in patients with a prior MI decreases in proportionto the deterioration in LVEF. The relative at rial contributionto left ventricular longitudinal distension is increased inpatients with a prior MI and diastolic mitral annular motionhas a significant relationship to the transmitral flow. Thesefindings suggest that mitral annular motion during late diastoleplays an important role in maintaining left ventricular fillingin patients whose left ventricular systolic function has deteriorated.     

Acoustic radiation force impulse under clinical conditions with single infusion of ultrasound contrast agent evoking arrhythmias in rabbit heart

Journal of Medical Ultrasonics - We previously reported that acoustic radiation force impulse (ARFI) with concomitant administration of perfluorobutane as an ultrasound contrast agent (UCA)-induced...     

Recent trends in cartilage regenerative medicine and its application to oral and maxillofacial surgery

Greater progress has been made in the clinical application of cartilage regenerative medicine, compared with that of other organs. A typical example of cartilage regenerative medicine is autologous chondrocyte implantation, in which chondrocytes isolated from the patient's cartilage are cultured and injected into the cartilage defects in a liquid- or gel-form. However, the classic autologous chondrocyte implantation has been applicable to only limited diseases, including focal cartilage lesion. Therefore, we developed “implant-type” tissue-engineered cartilage that shows mechanical strength and three-dimensional shape. This type of tissue-engineered cartilage uses scaffold composed of atelocollagen hydrogel and poly-l-lactic acid porous material, which is administered with cultured autologous auricular chondrocytes. Its clinical application to nasal deformity of cleft lip and palate patients has been ongoing at present. This review presents an overview of the current situation regarding cartilage regenerative medicine, as well as introducing our research and the development of implant-type tissue-engineered cartilage for the cleft-lip nose. The discussion of the future development of regenerative medicine is also mentioned.     

Percutaneous autologous concentrated bone marrow grafting in the treatment for nonunion

The purpose of this study was to evaluate the clinical and radiographic treatment effects of percutaneous autologous concentrated bone marrow grafting in nonunion cases and to evaluate the effectiveness of this grafting procedure. We enrolled 17 cases those had atrophic changes due to continuous nonunion for over 9 months after injury and had undergone low-intensity pulsed ultrasound treatment for more than 3 months. The site of nonunion was the femur in 10 cases, the tibia in 5 cases, the humerus in 1 case, and the ulna in 1 case. They underwent percutaneous autologous concentrated bone marrow grafting and continued low-intensity pulsed ultrasound stimulation treatment after grafting. Patients were evaluated using the visual analogue scale for pain at immediately before the procedure, 3, 6, and 12 months after grafting. Plain radiographs of the affected site were taken and evaluated about the healing of the nonunion site at each clinical evaluation. As quantitative assessment, CT scans were undertaken before the procedure and 6 months after grafting. The visual analogue scale pain score was reduced consistently after grafting in all patients. About the healing at the nonunion site, 11 and 13 cases of bone union were observed at 6 and 12 months after grafting. The mean volume of callus formation based on CT images was 4,147 (262–27,392) mm³ total between grafting and 6 months. Percutaneous autologous concentrated bone marrow grafting is an effective procedure for the treatment of patients with nonunion.     

Arsenite-induced thymus atrophy is mediated by cell cycle arrest: a characteristic downregulation of E2F-related genes revealed by a microarray approach.

Thymus atrophy is induced by a variety of chemicals, including environmental contaminants and is used as a sensitive index to detect their adverse effects on lymphocytes. In the present study we adopted a toxicogenomics approach to identify the pathways that mediate the atrophy induced by arsenite. We also analyzed gene expression changes observed in the course of thymus atrophy by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), dexamethasone (DEX), and estradiol (E2), to determine whether arsenite induces atrophy by activating an arsenite-specific pathway or the same pathways as other chemicals. These compounds were intraperitoneally administered to C57BL/6 mice at doses that reduce thymus weight by approximately 30% within 3 days, and gene expression changes in the thymus 24 h after the administration were analyzed by using microarrays and real-time PCR. The microarray analysis showed that arsenite specifically downregulates a variety of E2F target genes that are involved in cell cycle progression. The same genes were also downregulated when mouse B-cell lymphoma A20 cells were exposed to arsenite. Arsenite exposure of the A20 cells was confirmed to induce cell cycle arrest, mainly in the G(1) phase, and reduce cell number. Cell cycle arrest in the G(1) phase was also confirmed to occur in the thymocytes of the arsenite-exposed mice. These results indicate that arsenite induces thymus atrophy through E2F-dependent cell cycle arrest. The results of this study also show that analysis of gene expression in thymuses is a useful method of obtaining clues to the pathways that mediate the effects of atrophy-inducing chemicals.     

Central expression of c-Fos in neonatal male and female prairie voles in response to treatment with oxytocin

Early postnatal exposure to both exogenous and endogenous oxytocin (OT) can have long-term effects on behavior and physiology, although the mechanisms of these effects are not known. c-Fos expression was used to investigate the immediate neural effects of neonatal manipulations of OT in male and female prairie voles. On the day of birth prairie vole pups received an intraperitoneal injection of OT, a selective OT antagonist (OTA), or saline (vehicle control), while an additional group was handled but not injected. One hour after treatment brains were collected and fixed via spinning immersion and immunocytochemistry was then used to label for c-Fos immunoreactivity (IR). There were significant differences between males and females. Handled only females displayed significantly higher levels of c-Fos IR in the mediodorsal thalamic nucleus (MD) than males while handled males had higher c-Fos IR in the paraventricular nucleus of the hypothalamus than females. Exogenous OT stimulated neuronal activity in the supraoptic nucleus (SON) in males, while treatment with OTA increased Fos IR in the SON and was associated with reduced Fos IR in the MD in females. The results indicate that neuronal activity and responses to OT are sexually dimorphic in newborn prairie voles. In females changes in Fos expression were stimulated by treatment with OTA, suggesting that endogenous OT affects cellular activity while males responded to exogenous OT.     

Estrogen receptor alpha and vasopressin in the paraventricular nucleus of the hypothalamus in Peromyscus

The purpose of this study was to determine the presence of estrogen receptor alpha (ERalpha) and the relationship between neurons that express ERalpha and produce vasopressin (AVP) in the paraventricular nucleus of the hypothalamus (PVN) in new world mice of the genus Peromyscus. Brains were collected from male and female Peromyscus californicus, Peromyscus leucopus, Peromyscus maniculatus, and Peromyscus polionotus, and double labeled for the expression of ERalpha and AVP immunoreactivity (IR). The number of cells expressing ERalpha-IR and AVP-IR was determined in the medial and posterior region of the PVN. The results indicate that Peromyscus is the first taxonomic group reported to have ERalpha widely distributed in the PVN, occurring in both medial and posterior regions of the PVN. While estrogen can regulate the production of AVP, AVP and ERalpha were rarely colocalized. There was, however, a significant inverse relationship between the number of cells that expressed ERalpha-IR and the number expressing AVP-IR. There were no sex differences in the expression of ERalpha-IR or AVP-IR.     

Elevated frequency of sister chromatid exchanges of lymphocytes in sarin-exposed victims of the Tokyo sarin disaster 3 years after the event

We previously reported that the frequency of sister chromatid exchanges (SCEs) among victims of the Tokyo subway sarin disaster was significantly higher than that of controls 2-3 months after the disaster. It has been reported that the victims were also exposed to the by-products generated during sarin synthesis, i.e., diisopropyl methylphosphonate (DIMP), diethyl methylphosphonate (DEMP) and N,N-diethylaniline (DEA) during the disaster and we previously found that DIMP, DEMP and DEA induced a significant SCE increase in human lymphocytes in vitro. To monitor the genetic aftereffects of the sarin exposure, SCEs of peripheral blood lymphocytes were measured in fire fighters and police officers involved in the disaster 3 years after the event. We found that the frequency of SCEs was still significantly higher in the exposed subjects than the controls, suggesting a risk of the genetic aftereffects of the sarin exposure. We further found a significant positive correlation between the frequency of SCEs and the inhibition of serum cholinesterase activity in the exposed subjects, suggesting that the elevated frequency of SCEs is related to the sarin exposure. On the other hand, there was no significant difference in natural killer activity between the exposed and the controls.