Mamoru Ariyoshi

Vascular Endothelial Growth Factor in Patients with Rheumatoid Arthritis

To examine the role of vascular endothelial growth factor (VEGF), an endothelial cell specific growth factor, in rheumatoid arthritis (RA), serum concentration of VEGF was examined in patients with RA, osteoarthritis (OA), systemic lupus erythematosus (SLE), systemic sclerosis (SS) and control subjects. Serum C-reactive protein (CRP) level, erythrocyte sedimentation rate, white blood cell count and rheumatoid factor titer were also determined in patients with RA. The serum concentration of VEGF was significantly higher in patients with RA than in controls (p < 0.01), and patients with OA (p < 0.05), SLE (p < 0.05), and SS (p < 0.05). The serum concentration of VEGF correlated with serum levels of CRP (r = 0.698, p < 0.0001). The serum concentration of VEGF before treatment was significantly higher than that after treatment in patients with RA who experienced clinical remission (p < 0.05). Our data suggest that VEGF is involved in the pathogenesis of RA and that measurement of serum concentration of VEGF is a noninvasive, useful method for monitoring the disease activity of RA.

Percutaneous suction aspiration and drainage for pyogenic spondylitis

Study Design. Retrospective evaluation of results in 23 cases of early‐stage pyogenic spondylitis treated with percutaneous suction aspiration and drainage. Objectives. To evaluate the efficacy of percutaneous suction aspiration and drainage as a treatment method for early‐stage pyogenic spondylitis. Summary of Background Data. Traditional surgical treatment for pyogenic spondylitis has the disadvantage of increased morbidity caused by the extensive exposure required in the presence of infection. Recently, a few case reports have described minimally invasive treatment for pyogenic spondylitis in which percutaneous suction aspiration was used. However, the efficacy of this new treatment has not yet been evaluated. Methods. All charts, radiographs, and bacteriologic and histologic findings were reviewed. All 23 patients who received the new treatment were observed clinically and radiographically, to evaluate the efficacy of the treatment. Results. To date, all patients have been observed for more than 2 years. Twenty (87%) of the 23 patients have shown good results according to the evaluation. The causative organism was identified using tissue culturing in 12 (52%) of the 23 patients. The causative organism was Staphylococcus aureus in 8, and Staphylococcus epidermidis, Candida albicans, Pseudomonas aeruginosa, and Propionibacterium acnes in 1 each. Back pain as the major symptom in these patients was relieved within an average of 9.4 days after the operation. However, the patient in whom the spondylitis was caused by Candida albicans has received this new treatment twice without success. Conclusions. Evaluation of percutaneous suction aspiration with drainage shows that it is an effective treatment for early‐stage pyogenic spondylitis.

Glucocorticoid modulates the sensitivity of the GABAA receptor on primary afferent neurons of bullfrogs

With intracellular and voltage-clamp recording techniques, we have demonstrated that the glucocorticoids, prednisolone and hydrocortisone at a concentration of 5 microM to 1 mM, reversibly depressed gamma-aminobutyric acid (GABA)-induced responses on primary afferent neurons of bullfrogs. An analysis with dose-response curves revealed that the glucocorticoids decreased the sensitivity of the GABAA receptor in a non-competitive manner. We suggest that glucocorticoids act as an antagonist of the GABAA receptor on primary afferent neurons, probably by reducing the number of functional GABAA receptor ionic channel complexes.

Voltage-clamp studies of the inhibition of γ-aminobutyric acid response by glucocorticoids in bullfrog primary afferent neurons

Acute effects of glucocorticoids on the response to gamma-aminobutyric acid (GABA) were examined in primary afferent neurons in bullfrog spinal ganglia, using intracellular and voltage-clamp recording techniques. Prednisolone and hydrocortisone (5 microM to 1 mM) caused a dose-dependent decrease in the amplitude of GABA-induced depolarization, while having no effect on the membrane potential and resistance of the neuron. Prednisolone depressed the muscimol-induced depolarization. Nipecotic acid, a blocker of GABA uptake, did not influence the inhibitory action of prednisolone. Voltage-clamp analyses showed that the inward current induced by an iontophoretic application of GABA (GABA current) was suppressed by prednisolone and hydrocortisone. The depression of the GABA current is neither due to a blockage of open channels nor a facilitation of the desensitization of GABA receptors. Prednisolone shifted the dose-response curve of the GABA current downward. The double-reciprocal (Lineweaver-Burk) plot showed that the maximum GABA current was reduced by prednisolone, suggesting a non-competitive antagonism. These results suggest that glucocorticoids suppress the GABA-induced chloride current, decreasing the number of functional channels associated with GABAA receptor.

Presynaptic effects of cholecystokinin octapeptide on neuromuscular transmission in the frog

Intracellular recordings were obtained from the frog sartorius muscle end-plate to investigate the effects of cholecystokinin octapeptide (CCK-8) on cholinergic transmission at the neuromuscular junction. A brief bath-application of CCK-8 (1 microM) produced a depression, followed by a long-lasting facilitation, of the amplitude and the quantal content of the end-plate potential (epp). CCK-8 had a biphasic effect, an initial depression followed by an augmentation of the frequency of the miniature epps. CCK-8 did not affect the sensitivity of the nicotinic receptor at the end-plate. These results suggest a significant role for CCK-8 in cholinergic transmission, possibly as a modulator of the evoked release of acetylcholine from motor nerve terminals.

Chronic lumbar epidural hematoma in a patient who had spondylolysis at the third lumbar vertebra. Report of a rare case involving a seventeen-year-old adolescent.

A spinal epidural hematoma may result from one of many causes, including coagulopathy, trauma, a vascular lesion, iatrogenesis, and spontaneous occurrence2,4,6,7,11,12. Groen and van Alphen7 reviewed the cases of 333 patients who had a spontaneous spinal epidural hematoma; they had excluded patients in whom the hematoma had occurred after a traumatic episode involving spinal dislocation or fracture, after epidural anethesia, after diagnostic lumbar puncture, after an operation, or in association with a tumor in the spinal canal. Of the 333 patients, forty (12 per cent) had a lumbar epidural hematoma. Overall, fifty-five (17 per cent) of the patients were younger than twenty years old, and only four (7 per cent) of these young patients had a spontaneous lumbar epidural hematoma. Boyd and Pear reported that a hematoma caudad to the level of the conus medullaris was more likely to be chronic because the spinal roots appear to tolerate pressure better than the spinal cord does. In a review of the literature, we found four cases of lumbar epidural hematoma in patients who were younger than twenty years old3,7,17,21, and we compared these cases with that of our patient. A chronic spinal epidural hematoma is rare in young patients; it occurred in only two of the patients, including ours. We report the case of a young patient who had a chronic lumbar epidural hematoma and spondylolysis at the third lumbar vertebra. The patient, a seventeen-year-old high-school student, had radicular pain in the left lower extremity when he was first seen by us in 1991. He was a rugby player (center prop position number three), and, in early December 1991, he had pain on the left side of the low back …

Histamine as an endogenous antagonist of nicotinic ACh-receptor

The mechanism of an inhibitory effect of histamine on the sensitivity of frog skeletal muscle endplate was analyzed by studying the dose-response relation between the quantity of ACh applied iontophoretically and the ACh-induced postsynaptic current (ACh current), and also the interaction between histamine and erabutoxin-b (ETX-b). The results obtained show that histamine, like curare, decreased the sensitivity of ACh-receptor in a competitive manner.

Experimental external fixation combined with percutaneous discectomy in the management of scoliosis.

STUDY DESIGN An assessment of the value of external fixation with or without percutaneous discectomy for the management of scoliosis in young rabbits with induced progressive thoracic scoliosis. OBJECTIVES To investigate in an experimental setting the effect of external fixation with or without percutaneous discectomy for the management of scoliosis, as a preliminary study to precede clinical consideration. SUMMARY OF BACKGROUND DATA External fixation of the spine using percutaneous transpedicular screws has been used clinically for cases of traumatic spinal injury, infectious spine, or chronic low back pain caused by a disc lesion. Percutaneous discectomy for the management of scoliosis has been reported. METHODS Thirty-two young rabbits underwent partial resection of the right lower ribs. Nine rabbits were not treated after production of scoliosis and were followed as controls. At 4-6 weeks after production of scoliosis, in 23 animals, Kirschner wires were inserted percutaneously into the T9-T10 and L1-L2 disc space, and both ends were attached to an external fixator after correction of the scoliosis. In 8 of those 23 animals, percutaneous discectomy was also performed at the apex of the caudal compensatory curvature. RESULTS In these 23 animals, the initial correction by fixation on of the caudal vertebrae was accompanied by a derotation in the apex. Five animals treated with external fixation only and four treated with combined percutaneous discectomy survived with external fixation until the age of 17 weeks and were followed to the natural cessation of the curve progression, at which the fixation was removed and a final assessment was made. The mean progression of curvature was 15.8 degrees in the group of five animals with external fixation only, and 33.8 degrees in the controls. In the group of four animals treated with supplementary percutaneous discectomy, however, the treated disc space became rigid, and the mean progression of curvature after removal of the fixation was only 5.3 degrees. CONCLUSIONS The results of the current study suggest the potential for external fixation to allow for derotation and, when combined with percutaneous discectomy, to offer a feasible method of managing scoliosis in the human adolescent. This study was a preliminary experimental study; further experimental studies are planned to develop this novel technique.

Histamine is an antagonist of the acetylcholine receptor at the frog endplate.

1 The effects of histamine on the acetylcholine (ACh) receptor‐channel complex were examined by means of voltage‐clamp at the frog endplate. ACh was ionophoretically applied to the endplate. Histamine was added to the perfusate. 2 Histamine (100 nM − 1 mM) reversibly depressed the peak amplitude of the ACh‐induced inward current in a dose‐dependent manner. 3 The double reciprocal plot of the dose‐response relationship between the peak ACh current and the amount of ACh applied suggested that histamine (100 μM) depressed the ACh‐induced current in a competitive manner. 4 Histamine prevented the specific ACh binding site within the receptor‐channel complex from binding erabutoxin, a sea‐snake venom, which binds irreversibly to the specific ACh binding site. 5 Histamine had no detectable effects on the equilibrium potential of the endplate current but shortened the half‐decay time of the endplate current in a voltage‐dependent manner. 6 It was therefore concluded that histamine blocks not only the specific ACh binding site but also interacts with the ACh‐channel site. 7 The present experiments strongly suggest that histamine can act as an antagonist to modulate nicotinic cholinergic transmission.

Three stress fractures at different sites in the same tibia-a case report

An 8-year-old boy who had no significant past medical history had right leg pain for 2 months while practicing judo and with walking. He had been participating in 2 hours of judo practice twice a week and running almost every day for 2 years. He denied direct trauma to the leg. The anterior midshaft of the right leg was tender, without swelling or redness. Plain radiographs revealed a lucent area in the anterior cortex of the midshaft of the tibia. A bone scan with technetium-99 demonstrated locally increased uptake at the site of symptoms. MRI showed an abnormal signal intensity at the same spot. These findings were compatible with a stress fracture of the midanterior cortex of the tibia. He was treated with cast immobilization, no weight bearing and ambulation on crutches. The cast was removed after 2 months and he had no pain on standing, although he complained of mild tenderness over the anterior midshaft of the tibia. The lucent area was visible on repeated radiographs, but less distinct than on the initial radiographs. We removed the cast and permitted ankle motion, no weight bearing and use of crutches, but prohibited physical activities for 3 more months. 3 months later, he still had some pain and radiographs demonstrated a lucent area in the anterior cortex with linear sclerotic changes in the upper third of the tibia. We continued prohibition of weight bearing on the right leg for 2 more months. Nevertheless, 2 months later he still had pain and radiographs revealed sclerotic changes in the lower third of the tibia, in addition to findings in the midshaft and upper third. At that time, he confessed that he had been running now and then in order to maintain his competitive level with fellow athletes. We strictly prohibited weight bearing and sports activities, except swimming. 4 months later, he said he had been following our recommendation and had no symptoms and radiographs were normal. 1 year later he had no symptoms. He had a normal physical constitution, normal skin condition, normal ocular and auditory systems, normal laxity and range of motion in his joints, with normal alignment of his legs. Laboratory findings including blood count, sedimentation rate, calcium, phosphate, alkaline phosphate, thyroid and parathyroid hormones were normal. There was no evidence of rickets at the end of the long bones and bone density was normal.