Locomotive Syndrome: Operational Definition Based on a Questionnaire, and Exercise Interventions on Mobility Dysfunction in Elderly People.

The increasing elderly population has a great impact on public health, and it is important to understand the progression of musculoskeletal disorders seen in this population. To establish useful preventative methods for such locomotive disorders, we must detect early changes in these individuals and identify those at risk in order to implement early interventions. The purpose of this review was: (1) to introduce an operational definition of locomotion dysfunction to prevent a care-need condition, and to verify its validity through a prospective cohort study, and (2) to review the indication of exercise intervention for multiple musculoskeletal involvements from the preceding literature. We developed a measurement scale called the Geriatric Locomotive Function Scale (GLFS)-25, which clearly reflects the degree of functional deterioration. We used it in a prospective cohort study of 314 patients recruited from 5 clinics or nursing care facilities and investigated the relationship of the GLFS-25 with 46 variables covering various clinical manifestations. The results clearly revealed that the change in the GLFS-25 classification reflected a common pattern seen in those with locomotive dysfunction. Recently, several important movements regarding physical activity and its public promotion have been advocated by international health organizations and journal publishers. Though it has not been confirmed yet that complex musculoskeletal diseases can be treated using therapeutic exercise, the promotion of physical activity appears promising. The degree of activity limitation in aged individuals with locomotive disorders can be evaluated using this scale, which may be useful in predicting the effectiveness of future interventions.

Soft-plastic brace for lower limb fractures in patients with spinal cord injury.

STUDY DESIGN: Retrospective study at a rehabilitation center. OBJECTIVES: Patients with spinal cord injury, even if they are wheelchair users, sometimes suffer from fractures of the lower limb bones. As their bones are too weak to have surgery, and because a precise reduction is not required for restoration, such patients are often indicated for conservative treatment. This case series study investigated the use of a hinged, soft-plastic brace as a conservative approach to treating fractures of the lower extremities of patients with spinal cord injury. SETTING: National Rehabilitation Center, Japan. METHODS: Fifteen patients (male, n=10; female, n=5; average age, 52.7 years) with 19 fractures of the femur or the tibia who were treated with a newly-developed hinged, soft-plastic brace were studied. All of them used wheelchairs. We analyzed the time taken for fracture union and for wearing orthotics, degree of malalignment, femorotibial angle and side effects. RESULTS: The fractures in this series were caused by relatively low-energy impact. The average time taken for fracture union was 80.1 (37-189) days, and the average amount of time spent wearing orthotics was 77.9 (42-197) days. On final X-ray imaging, the average femorotibial angle was 176.9° (s.d. ±8.90), and 15° of misalignment in the sagittal plane occurred in one patient. CONCLUSION: A hinged, soft-plastic brace is a useful option as a conservative approach for treating fractures of the lower extremities in patients with spinal cord injury.

Phosphorylated neurofilament subunit NF-H as a biomarker for evaluating the severity of spinal cord injury patients, a pilot study.

STUDY DESIGN: A pilot cross-sectional study of patients with acute cervical spinal cord injury (SCI). OBJECTIVES: The precise evaluation of the severity of SCI is important for developing novel therapies. Although several biomarkers in cerebrospinal fluid have been tested, few analyses of blood samples have been reported. A novel biomarker for axonal injury, phosphorylated form of the high-molecular-weight neurofilament subunit NF-H (pNF-H), has been reported to be elevated in blood from rodent SCI model. The aim of this study is to investigate whether pNF-H values in blood can serve as a biomarker to evaluate the severity of patients with SCI. SETTING: Tokyo Metropolitan Bokutoh Hospital and National Rehabilitation Center, Japan. METHODS: This study enrolled 14 patients with acute cervical SCI. Sequential plasma samples were obtained from 6 h to 21 days after injury. Patients were classified according to American Spinal Injury Association impairment scale (AIS) at the end of the follow-up (average, 229.1 days). Plasma pNF-H values were compared between different AIS grades. RESULTS: In patients with complete SCI, pNF-H became detectable at 12 h after injury and remained elevated at 21 days after injury. There was a statistically significant difference between AIS A (complete paralysis) patients and AIS C (incomplete paralysis) patients. CONCLUSIONS: Plasma pNF-H was elevated in accordance with the severity of SCI and reflected a greater magnitude of axonal damage. Therefore, pNF-H is a potential biomarker to independently distinguish AIS A patients (complete SCI) from AIS C-E patients (incomplete SCI). However, further studies are required to evaluate its utility in predicting prognosis of patients in the incomplete category.

Hyperphosphorylated neurofilament NF-H as a biomarker of the efficacy of minocycline therapy for spinal cord injury.

STUDY DESIGN: An in vivo study in a rat model of acute spinal cord contusion. OBJECTIVES: To assess the efficacy of novel therapies for acute spinal cord injury (SCI), methods to evaluate accurately the effects of these therapies should be developed. Although neurological examination is commonly used for this purpose, unstable clinical conditions and the spontaneous recovery of neurological function in the acute and subacute phases after injury make this measurement unreliable. Recent studies have reported that the phosphorylated form of the high-molecular-weight neurofilament subunit NF-H (pNF-H), a new biomarker for axonal degeneration, can be measured in serum samples in experimental SCI animals. Therefore, we aimed to investigate the use of plasma pNF-H as an indicator of the efficacy of minocycline, a neuroprotective drug, for treating SCI. SETTING: This study was carried out at Saitama, Japan. METHODS: Spinal cord injured rats received either minocycline or saline intraperitoneally. The plasma pNF-H levels and functional hind limb score were determined after the injury. RESULTS: Minocycline treatment reduced plasma pNF-H levels at 3 and 4 days post-injury (dpi). Rats with lower plasma pNF-H levels at 3 dpi had higher hind limb motor score at 28 dpi. CONCLUSIONS: pNF-H levels may serve as a biomarker for evaluating the efficacy of therapies for SCI.

Statistical modelling of knee valgus during a continuous jump test.

Landing with the knee in a valgus position is recognized as a risk factor for anterior cruciate ligament (ACL) injury. Using linear and non-linear regression analyses, the purpose of this study was to examine the correlation between two-dimensional (2D) knee valgus and three-dimensional (3D) knee kinematics measured during a jump landing task. Twenty-eight female collegiate athletes participated. All participants were required to perform a continuous jump test. The average maximum angles of abduction and internal tibial rotation during landing were measured using the Point Cluster Technique. Average peak knee valgus angle was measured using a 2D approach. Linear and non-linear regression analyses between 2D valgus and 3D knee abduction, and between 2D valgus and 3D internal tibial rotation, were performed. The R2 value between 2D valgus and 3D knee abduction was significantly different from zero and had a moderate correlation for all models, whereas the R2 value between 2D valgus and 3D internal tibial rotation was not significantly different from zero. The 2D approach could be used to screen a specific group of individuals for risk of ACL injury; however, using frontal plane 2D analysis of valgus motion to evaluate internal tibial rotation is not advised.

A computer-controlled contracture correction device with low-load and continuous torque: an animal experiment and prototype design for clinical use.

The purpose of this study was to clarify the relationship between mechanical stress and tissue response of the contracted knee joint in rats and to propose a new design of contracture correction device for clinical use. Wistar rats were operated on to immobilize their knee joints with a procedure causing periarticular bleeding and were kept in flexed position for 40 days. At day 40, the immobilizing wire was removed, and after day 43, the contracted knee joint had been treated with tunable corrective devices secured by an external fixation method to the rear limb. These devices consisted of four types of motor-driving system which provided several different low-load and continuous stretch torques. Measuring the angle of maximum knee extension, its effectiveness was assessed comparing with a lower load and control group of natural recovery course. The device also had a cyclic joint movement within the acquired range of motion and an oval cam mechanism producing a small distraction force to the joint along its long axis. The results showed that an appropriate range of low-load continuous torque was more effective to correct joint contracture. On the basis of the animal experiment, a new computer-controlled, gas-driven contracture correction device was developed for clinical trial. It was concluded that mechanical application in a condition with low and continuous torque is a useful treatment for fixed joint contracture.

Leukotoxin (9, 10-epoxy-12-octadecenoate) impairs energy and redox state of isolated perfused rat lung.

We investigated the perturbation of energy balance and redox state in leukotoxin (9, 10-epoxy-12octadecenoate) (Lx)- and endothelin-1 (ET-1)-induced lung injury, using isolated perfused rat lungs. To examine any relationship between these parameters, intracellular levels of adenine nucleotides, pyridine coenzymes and glutathione were determined by reversed-phase high-performance liquid chromatography (HPLC) in the freeze-dried tissues of isolated rat lungs. The tissue samples were perfused with a physiological salt solution containing either Lx only, Lx plus NG-monomethyl-L-arginine (L-NMMA), Lx plus NG-monomethyl-D-arginine (D-NMMA), Lx plus superoxide dismutase (SOD) or ET-1 only. In isolated perfused lung tissue, 10 mol of Lx caused permeability-increased lung injury, and 10 nM of ET-1, which caused a comparable increase in wet lung weight, evoked pulmonary capillary hypertensive lung injury. Lx-injured lungs showed decreases in the contents of ATP, NADPH, NADH, reduced glutathione (GSH), (2ATP + ADP)/2(ATP + ADP + AMP) ratio (energy charge) and NADH/NAD+ ratio, and increased the contents of ADP and AMP compared with the vehicle control and ET-1-injured lungs. Such effects of Lx were significantly attenuated by pretreatment with 0.4 mM L-NMMA or 500 units/ml of SOD, but not with 0.4 mM D-NMMA. On the other hand, the ET-1-injured lung evidenced decreased tissue GSH. These findings indicate that Lx shifted the lung redox state toward oxidation and that Lx-induced lung injury was involved in the imbalance of the energy and redox state via production of nitric oxide and/or superoxide anion.

Adrenal and gonadal function in hypothyroid adult male rats.

The functional relationship between thyroid, adrenal and gonadal hormones was investigated using adult male rats. Hypothyroidism was produced by the administration of 4-methyl-2-thiouracil (thiouracil) in the drinking water for 2 weeks. Plasma concentrations of TSH dramatically increased, whereas plasma concentrations of tri-iodothyronine and thyroxine decreased in thiouraciltreated rats as compared with euthyroid rats. Hypothyroidism increased basal levels of plasma ACTH and pituitary content of ACTH. The pituitary responsiveness to CRH for ACTH release markedly increased, whereas the adrenal responsiveness to ACTH for corticosterone release decreased. These results indicated that hypothyroidism causes adrenal dysfunction in adult male rats. Pituitary contents of LH and prolactin decreased in hypothyroid rats as compared with euthyroid rats. In addition, hypothyroidism lowered pituitary LH responsiveness to LHRH. Testicular responsiveness to human chorionic gonadotrophin for testosterone release, however, was not different between euthyroid and hypothyroid animals. These results indicated that hypothyroidism causes adrenal dysfunction and results in hypersecretion of ACTH from the pituitary gland. Adrenal dysfunction may contribute to the inhibition of LHRH secretion from the hypothalamus, possibly mediated by excess CRH.

Influences of bradykinin and substance P on the met-enkephalin-like peptide content in the rat incisor pulp.

The present study was aimed to examine possible influences of bradykinin (BK) and substance P (SP) on met-enkephalin (ME)-like peptide content in the rat incisor pulp. Des-Arg9-[Leu8]-BK, a potent BK-antagonist, significantly reduced the increased content of ME-like peptides induced by noxious stimulation, while the effect of BK-antagonist was reversed in combination with BK. Morphine decreased the increased content of ME-like peptides. Ethylketocyclazocine, a kappa-agonist, also decreased the increased content of the peptides. From these results, it was suggested that BK might be a trigger in the increase of ME-like peptide content induced by noxious stimulation and, in contrast, ME-like peptides in the pulp might inhibit BK release from the pulp in a negative feedback mechanism. On the other hand, [D-Pro2,D-Trp7,9]-SP, a potent SP-antagonist, did not show any significant influence to ME-like peptide content in the pulp. Furthermore, the content was not changed following cutting of inferior alveolar nerve. From these results, it was suggested that ME-like peptides in the pulp cells might be independent on SP-containing nerves in the pulp.

Carbonic anhydrase activity in the trigeminal primary afferent neuronal cell bodies with peripheral axons innervating the mandibular molar tooth pulps of the rat.

Trigeminal primary afferent neuronal cell bodies were labeled with FITC-WGA retrogradely transported from the mandibular molar tooth pulp (tooth pulp) and the cutaneous branch of the mylohyoid nerve (cutaneous nerve) in the rat. Tissue sections were then incubated in Hansson's medium for histological demonstration of carbonic anhydrase (CA) activity. About 85% of primary neurons innervating the tooth pulp had medium to large cell bodies (greater than or equal to 300 microns 2 in cross-sectional area), while 77% of those innervating the cutaneous nerve were small (less than 300 microns 2). A total of 32% of the tooth pulp cells exhibited CA activity. CA-containing cells constituted only about 4% of the cutaneous nerve cells. In view of the known distribution of CA within the rodent nervous system, the CA-containing cells are considered to represent the tooth pulp primaries conducting in A-beta velocity range and projecting to rostral subdivisions of the brainstem sensory trigeminal nuclear complex.

Re-innervation of rat molar tooth pulp following transection of the inferior alveolar nerve.

The inferior alveolar nerves (IAN) of young male Wistar rats (b.wt. greater than or equal to 200 g) were transected unilaterally, slightly proximal to the mandibular foramen under anesthesia with chloral hydrate (0.4 g/kg, i.p.). After various postoperative periods of time, the animals received horseradish peroxidase (HRP) applications to 3 mandibular molar tooth pulps on both sides and were fixed by transvascular perfusion 24 h later. Horizontal 60 microns sections of the trigeminal ganglion were incubated with tetramethylbenzidine hydrochloride and the cross-sectional areas of all the labeled neuronal cell bodies were measured. The average number of labeled cells on the untransected (control) side was 148 (n = 26), with cross-sectional areas ranging between 131.9 and 2129.6 microns 2. Of these, 42.5% fell between 300 and 600 microns 2. About 13.5% (n = 7) of the primary neurons innervating the tooth pulps escaped the ipsilateral neurotomy and were labeled by HRP application on postoperative day 0. With HRP application on postoperative day 3, the number of labeled neurons recovered to 56.8% (n = 7) that of the control and maintained this level up to postoperative day 75. From postoperative days 3 through 75, the cell size spectrum of labeled neurons on the transection side was similar to that of the control and no consistent tendency of alteration was observed; i.e. they were distributed between 134.4 and 2214.3 microns 2, with the mode being 41.5% in the range between 300 and 600 microns 2 (n = 19).

Coexistence of vasoactive intestinal polypeptide- and substance P-like immunoreactivities in the tongue of the guinea pig.

Vasoactive intestinal polypeptide (VIP)- and substance P (SP)-like immunoreactivities were examined in the tongue of the guinea pig by using the double immunofluorescence method. Coexistence of VIP- and SP-like immunoreactivities was suggested in many nerve fibers innervating the lingual salivary glands, as well as in a few intralingual ganglionic cells.

Aversive taste stimuli increase CGRP levels in the gustatory insular cortex of the rat.

Calcitonin gene-related peptide-like immunoreactivity (CGRP-IR) was surveyed immunohistochemically in the insular cortex of the rat, and the levels of insular cortical CGRP-IR were measured with the radioimmunoassay method following intraoral stimulation with various taste stimuli. CGRP-IR was localized in nerve fibers within the agranular and dysgranular insular cortices. The CGRP-IR levels in the rostral (gustatory) part of the insular cortex were increased significantly by strongly aversive taste stimuli such as quinine hydrochloride and conditioned taste stimuli (NaCl and sucrose) which animals had been taught to avoid. The results suggest that CGRP in the gustatory insular cortex is concerned with rejection or avoidance behaviors to aversive taste stimuli.

The influence of vanadate on calcium uptake in maturing enamel of the rat incisor.

The influence of vanadate, a potent inhibitor of Ca2+-ATPase and Na+-K+-ATPase, on 45Ca uptake in maturing enamel of the rat incisor was investigated by a vascular perfusion method combined with 45Ca autoradiography. The morphological integrity of the maturation-stage enamel organ was well-retained during vascular perfusion under all the experimental conditions. Distinct patterns of 45Ca labeling, comparable with those found in previous in vivo 45Ca autoradiographic studies, appeared in the maturing enamel after vascular perfusion with a standard perfusate. One mmol/L vanadate added to the standard perfusate caused a drastic decrease in 45Ca uptake in the maturing enamel, corresponding to the ruffle-ended ameloblasts, leaving narrow peaks of moderate intensity corresponding to the bands of the overlying smooth-ended ameloblasts. The in vitro labeling of exposed enamel surfaces with 45Ca revealed blackening of autoradiographic emulsion in wide bands separated by unlabeled or slightly labeled narrow ones resembling the distribution of smooth-ended ameloblasts in both control and vanadate-treated incisors. Our observations indicate that the ruffle-ended ameloblasts of the rat incisor serve as an efficient diffusion barrier to calcium ions and regulate transcellular calcium transport to the maturing enamel, at least in part, by a vanadate-sensitive mechanism.

Membranous lipodystrophy: a clinicopathological study of six cases.

Membranous lipodystrophy apparently is a new disease, first reported and named by Nasu and associates 31 in 1971. We have collected six cases of this disease. The initial manifestation was articular pain at adolescence. Symmetrical changes in the bones of the extremities then appeared and the disease seemed to progress slowly with age. The younger patients exhibited only skeletal pain or fractures, while the older patients had some neuropsychiatric changes. Three of the patients died in middle age. The cystic bone lesions contained a yellow, lipid-like substance which histologically showed a characteristic membranocystic appearance. Electron microscopic study showed unique features, but biochemical analysis of the substance did not reveal a definable abnormality.

Immunohistochemical observation on neuropeptides around the blood vessel in feline dental pulp.

Recent advances in immunohistochemistry have revealed the distribution of various neuropeptides in several mammalian dental pulps. These neuropeptides are substance P, neurokinin A, calcitonin gene-related peptide, vasoactive intestinal polypeptide, and neuropeptide Y. Nerve fibers showing immunoreactivity for these neuropeptides are mainly localized around the pulpal vessels, but some are apart from the blood vessel. The distribution of substance P-, neurokinin A-, and calcitonin gene-related peptide-containing nerve fibers is very similar; it appears that these three neuropeptides may be contained in the same nerve fibers. Denervation experiments indicate that substance P-, neurokinin A- and calcitonin gene-related peptide-containing nerve fibers originate from the trigeminal ganglion and that neuropeptide Y-containing nerve fibers come from the superior cervical ganglion. However, the exact origin of vasoactive intestinal polypeptide-containing fibers still remains unknown. These immunohistochemical data indicate that neuropeptides localized around the blood vessel may play a significant role in the regulation of the blood flow in the dental pulp.

Neuropeptide Y- and substance P-like immunoreactivities in the guinea pig parotid gland.

These immunoreactivities were examined by double immunofluorescence, which demonstrated that many nerve fibres around the glandular acini and blood vessels contain neuropeptide Y and substance P. It appears that these substances may coexist in nerve fibres around acini, but that there may be two populations of fibres containing these peptides around the blood vessels.

Fine structure of calcitonin gene-related peptide-immunoreactive nerve fibres in the rat temporomandibular joint.

The distribution and fine structure of these nerve fibres was examined by immunoelectron microscopy. CGRP-immunoreactive fibres were seen in the nerve bundles, blood vessels and periosteum around the condyle as well as in the disc. These nerve fibres were unmyelinated and had diameters varying from 200 to 600 nm. They were completely or partially enclosed by Schwann cell cytoplasm and did not form synaptic contact with any cells. CGRP-immunoreactive nerve fibres may be sensory nature and this peptide could be involved in pain transmission and neurogenic inflammation.

Cytochemical study of the Golgi apparatus and related organelles of the secretory ameloblasts of rat molar tooth germs cultured with and without colchicine.

The Golgi apparatus and Golgi-associated endoplasmic reticulum lysosome (GERL) were examined in the ameloblasts with a cytochemical marker, osmium impregnation, and two enzyme markers, thiamine pyrophosphatase (TPPase) and acid phosphatase (ACPase). In control cultured germs, osmium deposit appeared in one to two immature side cisternae of Golgi stacks; TPPase activity was restricted in a few mature side cisternae and condensing vacuoles. ACPase activity existed in the GERL and, sometimes, in the mature side-cisternae and condensing vacuoles. These findings show that Golgi stacks of ameloblasts consist of several distinct compartments. In colchicine-treated tooth germs, there were morphological and cytochemical changes in both Golgi stacks and GERL. The Golgi apparatus was fragmented and its stacks were scattered throughout the supranuclear region. In some stacks, the number of osmium-positive cisternae was greater than normal; in others they were absent. TPPase and ACPase activity was absent or diminished. These findings suggest the importance of microtubules in the organization of Golgi complex and GERL in the secretory ameloblast.