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Biomedical subjects

K Ogawara

Publications and source records attributed to K Ogawara.

At least 19 recordsLinked to original sources

Abnormal muscle responses in hemifacial spasm: F waves or trigeminal reflexes?

OBJECTIVE: In patients with hemifacial spasm (HFS), abnormal muscle responses (AMR) are frequently present. The objective of this study was to investigate whether the afferent input of AMR is mediated by antidromic facial nerve stimulation or orthodromic trigeminal nerve stimulation. METHODS: AMR in the orbicularis oris muscle were recorded in 28 patients with HFS. When AMR were present, they were recorded after subthreshold stimulation of the facial nerve and weak stimulation delivered to the skin. RESULTS: AMR were recordable in 24 (86%) of the patients, and usually consisted of the early constant component (mean onset latency, 10.0 ms) and late variable component (35.3 ms), similar to R1 and R2 of the blink reflex. The early or late components of AMR, or both, were frequently elicited after subthreshold stimulation of the facial nerve (43%) and skin stimulation (88%). CONCLUSIONS: AMR are likely to be mediated by trigeminal afferent inputs, rather than antidromic activation of the facial nerve, and are a type of trigeminal reflex.

Adult↗

Monitoring of circulating tumour-associated DNA as a prognostic tool for oral squamous cell carcinoma.

Frequent allelic imbalances (AIs) including loss of heterozygosity and microsatellite instability on a specific chromosomal region have been identified in a variety of human malignancies. The objective of our study was to assess the possibility of prognostication and monitoring of oral squamous cell carcinoma (SCC) by microsatellite blood assay. DNA from normal and tumorous tissues and serum DNA obtained at three time points (preoperatively, postoperatively, and 4 weeks postoperatively) from 64 patients with oral SCC was examined at nine microsatellite loci. In all, 38 (59%) DNA samples from tumorous tissues and 52% from serum showed AIs in at least one locus. Patterns of AIs in the serum DNA were matched to those detected in tumour DNA. Of them, AIs were frequently detected preoperatively (44%, 28 of 64), and postoperatively (20%, 13 of 64). Moreover, among 12 cases with AIs during the postoperative period, six had no evidence of an AI 4 weeks postoperatively, and they had no recurrence and were disease free. In contrast, six patients with AI-positive DNA 4 weeks postoperatively have died with distant metastasis within 44 weeks. Thus, our results suggest that the assessment of microsatellite status in the serum DNA could be a useful predictive tool to monitor disease prognosis.

Adult↗

Patterns and serial changes in electrodiagnostic abnormalities of axonal Guillain-Barré syndrome.

BACKGROUND: In Guillain-Barré syndrome (GBS), anti-ganglioside antibodies are strongly associated with the acute motor axonal neuropathy (AMAN) form, but there are also cases of the demyelinating form of GBS (acute inflammatory demyelinating polyneuropathy [AIDP]) with anti-ganglioside antibodies. OBJECTIVE: To elucidate the patterns and sequential changes in electrodiagnostic abnormalities of anti-ganglioside-positive GBS. METHODS: Detailed serial electrodiagnostic findings were reviewed for 51 patients with GBS. Anti-ganglioside antibodies were measured by ELISA. RESULTS: Antibodies to GM1, GM1b, GD1a, or GalNAc-GD1a were present in 25 patients. Of these, 12 (48%) showed the AMAN pattern, 5 (20%) the AIDP pattern, and 3 (12%) isolated F-wave absence in the first examination. All five patients with the AIDP pattern showed prolonged distal latencies, but three eventually showed the AMAN pattern or rapid normalization. The remaining two still had similarly prolonged distal latencies in weeks 4 to 6, but the serial changes were distinct from those in the anti-ganglioside-negative AIDP patients who showed progressive increases in distal latencies over 2 months after onset. CONCLUSIONS: Besides the simple axonal degeneration pattern, patients with anti-ganglioside-positive Guillain-Barre syndrome can show transient conduction slowing/block in the distal or proximal nerve segments, mimicking demyelination, but anti-ganglioside antibodies do not appear to be associated with acute inflammatory demyelinating polyneuropathy.

Adult↗

Recovery patterns and long term prognosis for axonal Guillain-Barré syndrome.

BACKGROUND: Little is known about the long term prognosis for patients the severe acute motor axonal neuropathy (AMAN) form of Guillain-Barré syndrome (GBS), unlike those with acute inflammatory demyelinating neuropathy (AIDP). OBJECTIVE: To clarify the long term prognosis for patients with AMAN. METHODS: Clinical recovery and outcome in 97 consecutive GBS patients were reviewed. RESULTS: Electrodiagnostic criteria showed that 44 patients (45%) had AMAN, 33 (34%) had AIDP, and 20 (21%) were unclassified. Most of the severely affected patients had received plasmapheresis or immunoglobulin therapy. Slow recovery (inability to walk independently at six months after onset) was found in six of the AMAN patients (14%) and in two of the AIDP patients (6%). Of the six AMAN patients, four could walk independently one year after the onset, and the other two could walk independently at 28 and 57 months after onset. Of the two AIDP patients, one could walk at nine months after the onset while the other died of pneumonia seven months after onset. CONCLUSIONS: AMAN electrodiagnosis is not always a marker of poor recovery. Almost all the severe AMAN patients who had slow recoveries over the first six months could eventually walk independently, although some required several years.

Adolescent↗

Enhancement of topical delivery of drugs via direct penetration by reducing blood flow rate in skin.

The purpose of this work was to investigate the effect of blood flow in the skin on the direct penetration of topically applied drugs into the muscular layer, and to show that the skin blood flow could also be one of the important factors determining the direct penetration of drugs to the muscular layer. In vivo percutaneous absorption study was performed for antipyrine, salicylic acid or diclofenac by using rats with tape-stripped skin. Phenylephrine, which is well known to reduce the local blood flow by vasoconstrictor action, was topically applied to decrease the local blood flow in the skin. The concentrations of drugs in viable skin and muscle, and the local blood flow in the skin under the applied and the contralateral sites were determined to evaluate the effect of the local blood flow on the delivery of topically applied drugs into the muscular layer. Dose dependency for the effect of phenylephrine was, first of all, investigated for antipyrine in the range from 0.4 to 10 micromol. The distribution of antipyrine into the viable skin and muscular layer 2 h after topical application significantly increased, but the effect of phenylephrine was saturated around 2 micromol and the dose-dependent profiles for both tissues were almost superimposed. On the other hand, the fraction dose absorbed, plasma concentration and concentrations in viable skin and muscular layer under the contralateral site showed the decreasing tendency and the saturation of the effect around 2 micromol. To confirm the effect of phenylephrine on the local blood flow in the skin, the skin blood flow was measured 2 h after topical application of 2 micromol phenylephrine, and the significant decrease in the blood flow was recognized. In vivo percutaneous absorption studies were performed for salicylic acid and diclofenac, too. Extensive enhancement of penetration into the viable skin and muscular layer was observed for both drugs, although total absorption from the donor cell showed the decreasing tendency. In conclusion, direct penetration of drugs applied topically is enhanced by reducing the local blood flow in the skin, which would be a possible approach to improve the local delivery of drugs applied topically.

Administration, Topical↗

Does Campylobacter jejuni infection elicit "demyelinating" Guillain-Barre syndrome?

BACKGROUND: Campylobacter jejuni enteritis is the most common antecedent infection in Guillain-Barré syndrome (GBS). C. jejuni-related GBS is usually acute motor axonal neuropathy (AMAN), but previous reports described many cases of the demyelinating subtype of GBS (acute inflammatory demyelinating polyneuropathy [AIDP]) after C. jejuni infection. OBJECTIVE: To investigate whether C. jejuni infection elicits AIDP. METHODS: In 159 consecutive patients with GBS, antibodies against C. jejuni were measured using ELISA. Antecedent C. jejuni infection was determined by the strict criteria of positive C. jejuni serology and a history of a diarrheal illness within the previous 3 weeks. Electrodiagnostic studies were performed weekly for the first 4 weeks, and sequential findings were analyzed. RESULTS: There was evidence of recent C. jejuni infection in 22 (14%) patients. By electrodiagnostic criteria, these patients were classified with AMAN (n = 16; 73%) or AIDP (n = 5; 23%) or as unclassified (n = 1) in the first studies. The five C. jejuni-positive patients with the AIDP pattern showed prolonged motor distal latencies in two or more nerves and had their rapid normalization within 2 weeks, eventually all showing the AMAN pattern. In contrast, patients with cytomegalovirus- or Epstein-Barr virus-related AIDP (n = 13) showed progressive increases in distal latencies in the 8 weeks after onset. CONCLUSION: Patients with C. jejuni-related Guillain-Barré syndrome can show transient slowing of nerve conduction, mimicking demyelination, but C. jejuni infection does not appear to elicit acute inflammatory demyelinating polyneuropathy.

Adolescent↗

Trigeminal afferent input alters the excitability of facial motoneurons in hemifacial spasm.

OBJECTIVE: To investigate whether skin or muscle afferent input via the trigeminal nerve alters the excitability of facial motoneurons in hemifacial spasm (HFS). METHODS: Botulinum toxin type A (BTX) was injected only to the orbicularis oculi (O. oculi) muscle of 21 patients with idiopathic HFS, and the excitability of the orbicularis oris (O. oris) motoneurons was monitored. The synkinetic response (SR) of the blink reflex and abnormal muscle response (AMR) were recorded from the O. oris before and after treatment. RESULTS: BTX injections produced marked to moderate improvement in the O. oculi of all 21 patients and in the O. oris of 17 (81%). The rectified areas of SR1 and SR2 were smaller after treatment. In particular, the AMR area showed a reduction (p = 0.02). CONCLUSIONS: The significant lessening of spasms in the O. oris after BTX injection to the O. oculi and the concomitant reduction in excitability of O. oris neurons are consistent with the hypothesis that in HFS, skin or muscle afferent volleys via the trigeminal nerve enhance the excitability of facial nerve motoneurons.

Action Potentials↗

Differences in patterns of progression in demyelinating and axonal Guillain-Barré syndromes.

BACKGROUND: Immune treatments are recommended for patients with Guillain-Barré syndrome (GBS) who cannot walk independently, but a considerable number of GBS patients are in the progressive phase at the first examination. OBJECTIVE: To investigate whether progression patterns differ in demyelinating and axonal subtypes of GBS. METHODS: Clinical, laboratory, and electrophysiologic data on 131 consecutive patients with GBS were reviewed. Patients were classified as having acute inflammatory demyelinating polyneuropathy (AIDP) or acute motor axonal neuropathy (AMAN) based on electrodiagnostic criteria. RESULTS: Forty-one patients had AIDP, 62 AMAN, and 28 were unclassified. Age, sex, and Hughes Functional Grading Scale score at the first medical examination did not differ for the AIDP and AMAN patients. Mean periods between neurologic onset and first examination (5.3 vs 4.2 days; p = 0.01) and neurologic onset and nadir (18.0 vs 11.5 days; p = 0.001) were longer for the AIDP group. In the subgroup of those with mild disability (able to walk independently at the first neurologic examination), 88% of the AMAN patients had reached the nadir, whereas 65% of the AIDP patients had reached it. The remaining 35% progressed to it over the next 1 to 2 weeks and were unable to walk at nadir. CONCLUSIONS: The patterns and speeds of progression differ in AMAN and AIDP, AMAN having a rapid progression and an early nadir. AIDP patients frequently have a significantly long progression after the first examination; therefore, they need to be carefully monitored.

Acute Disease↗

Properties of human skin mechanoreceptors in peripheral neuropathy.

OBJECTIVES: To investigate the properties of mechanoreceptors in patients with peripheral neuropathy. The skin mechanoreceptor is a terminal organ of the primary sensory neuron, which is likely to be affected earlier and more severely than is the nerve trunk by peripheral neuropathies. METHODS: Single sensory unit responses to air-puff and electric stimulation were recorded using the microneurographic technique in the glabrous skin of the hand. Receptor transduction time was estimated by a latency difference between electric- and air-puff-induced responses. RESULTS: A total of 38 mechanoreceptive units were obtained from 14 normal subjects. All the units responded to air-puff stimuli irrespective of the receptor type, and receptor transduction time was approximately 2 ms. A total of 32 units were recorded from 11 patients with neuropathy of variable causes. Seven (22%) of the 32 neuropathic units did not respond to air-puffs despite their ability to respond to electric stimulation. Compared to normal ones, units from patients with peripheral neuropathy had significantly higher mechanical thresholds, but receptor transduction times did not differ significantly. CONCLUSIONS: Changes in receptor properties in human neuropathy are characterized by increased mechanical threshold without prolongation of receptor transduction time, possibly due to a high threshold for generating receptor potentials.

Aged↗

Distribution patterns of demyelination correlate with clinical profiles in chronic inflammatory demyelinating polyneuropathy.

BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a heterogeneous disorder having a wide clinical range, and is characterised by multifocal demyelination that can involve the distal nerve terminals, intermediate nerve segments, and nerve roots. OBJECTIVE: To investigate whether the distribution patterns of demyelination along the course of the nerve correlate with clinical profiles in patients with CIDP. METHODS: Motor nerve conduction studies were carried out on 42 consecutive patients. According to the physiological criteria for demyelination, the presence of a demyelinative lesion was determined in the distal nerve segments (distal pattern) or intermediate nerve segments (intermediate pattern), or in both (diffuse pattern). The serum concentration of tumour necrosis factor (TNF)-alpha was measured by immunoassay. RESULTS: Patients were classified as having a distal (n=10), intermediate (n=13), or diffuse (n=15) pattern, or were unclassified (n=4). Patients with the distal or diffuse pattern had common clinical features such as subacute onset, symmetric symptoms, and weakness involving proximal as well as distal muscles. Patients with the distal pattern had a good response to treatment and a monophasic remitting course, but the diffuse pattern was associated with a treatment dependent relapsing course, reflecting longer disease activity. The serum TNF-alpha concentrations increased only in the "diffuse" subgroup of patients, and this might be associated with breakdown of the blood-nerve barrier and therefore, involvement of the intermediate segments. The intermediate pattern was characterised by a chronic course, asymmetric symptoms, less severe disability, and refractoriness to treatments. CONCLUSIONS: CIDP consists of subtypes with varying predilections for lesions along the course of the nerve. The distribution patterns of conduction abnormalities may be useful in the prediction of outcome of patients with CIDP.

Adolescent↗

Surface hydrophobicity of particles is not necessarily the most important determinant in their in vivo disposition after intravenous administration in rats.

The in vivo disposition of polystyrene microsphere (MS) with the particle size of 50 nm (MS-50) and lecithin-coated MS-50 (LMS-50) after intravenous administration to rats was characterized. While a rapid elimination from the systemic circulation was observed for MS-50, much more prolonged circulating property was observed for LMS-50. In addition, this in vivo disposition property of LMS-50 was suggested to be ascribed to its lower affinity to the liver, which is the determining organ of the in vivo disposition of MS-50. The evaluation of surface hydrophobicity of MS-50 and LMS-50 in buffer solution revealed that the surface of MS-50 is more hydrophobic than that of LMS-50. However, LMS-50 was oppositely found to be more hydrophobic than that of MS-50 in rat serum. The profiles of serum proteins associated with MS-50 and LMS-50 were also examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The results showed that the amounts of some adsorbed proteins are greatly different between MS-50 and LMS-50. From these findings, it was suggested that the substantial difference in the in vivo disposition between MS-50 and LMS-50 would not be attributed to the difference in their surface hydrophobicity in the blood, but the difference in the type of serum proteins associated with them.

Animals↗

Biliary excretion of polystyrene microspheres depends on the type of receptor-mediated uptake in rat liver.

Hepatic uptake and biliary excretion of fluorescein isothiocyanate-labeled polystyrene microspheres with a particle size of 50 nm (MS-50) were studied in rats. Liver perfusion studies revealed that not only apo-E-mediated but also asialoglycoprotein receptor-mediated uptake is involved in the mechanism of the serum protein-dependent uptake of MS-50 in the liver. The uptake of MS-50 mediated by apo-E contributes more to the total uptake of MS-50 by the hepatocytes than that via asialoglycoprotein receptor in the presence of serum in the perfusate. Furthermore, it was found that MS-50 is substantially excreted into the bile by transcytosis. The extent of exocytosis of MS-50 taken up by the hepatocytes was much higher after MS-50 was endocytosed via asialoglycoprotein receptor than after taken up via the process mediated by apo-E. On the basis of these results, a possible regulation of the intracellular sorting of ligands, depending on the receptor-mediated uptake mechanism, was inferred.

Animals↗

Intravenous immunoglobulin therapy for Guillain-Barré syndrome with IgG anti-GM1 antibody.

To compare the effects of intravenous immunoglobulin (IVIg) therapy and plasmapheresis for the IgG anti-GM1-positive subtype of Guillain-Barré syndrome (GBS), clinical and electrophysiological recoveries were analyzed in 24 patients treated with IVIg (n = 10) or plasmapheresis (n = 14). At entry, there were no significant differences between the two patient groups in age, sex, clinical severity (Hughes grade), sum scores of distally evoked amplitudes of compound muscle action potentials (CMAPs), and frequency of Campylobacter jejuni infection. The patients treated with IVIg had significantly lower Hughes grade scores 1, 3, and 6 months after onset (P = 0.03), and a higher probability to regain independent locomotion at 6 months [P(logrank) = 0.044]. In the IVIg group, markedly rapid recovery (improvement by two or more Hughes grade scores within 4 weeks) was more frequent (6 of 10 vs. 3 of 14, P = 0. 03), and delayed recovery (unable to walk independently at 6 months) was less frequent (0 of 10 vs. 4 of 14, P = 0.06). CMAP sum score at 6 months tended to be greater for the IVIg group (P = 0.07). For the IgG anti-GM1-positive subgroup of GBS patients, IVIg therapy may be a more efficacious treatment than plasmapheresis.

Action Potentials↗

Mechanisms of early and late recovery in acute motor axonal neuropathy.

Motor unit number estimate (MUNE) of the abductor pollicis brevis (APB) was sequentially performed in seven patients with acute motor axonal neuropathy (AMAN). The MUNE markedly decreased (mean, 11) at the peak of the illness. Clinical recovery of APB strength began during week 4, with an increase in amplitude of distal compound muscle action potentials. The MUNE did not change significantly in this early recovery phase and increased slowly with time. The main mechanism for early recovery in AMAN may be collateral reinnervation, with nerve regeneration developing later.

Action Potentials↗

Amino acids protect epithelial cells from local toxicity by absorption enhancer, sodium laurate.

To develop the safe absorption-enhancing formulation attenuating the local toxicity caused by an absorption enhancer, sodium laurate (C12), the effects of amino acids on the local toxicity by C12 were examined in rats. The absorption of phenol red, an unabsorbable marker drug, was significantly enhanced by 10 mM C12 in an in situ colon loop study and the addition of L-glutamine (L-Gln), L-arginine, or L-methionine at 10 mM did not change the promoting effect of C12. However, C12 significantly increased the elution of phospholipids, total protein, and lactate dehydrogenase, which are markers for local toxicity, from colon, but these amino acids attenuated the local toxicity caused by C12 significantly. Transport study using an Ussing-type chamber showed that the permeability of colonic membrane to phenol red was significantly enhanced by C12 and that L-Gln did not decrease the permeability enhanced by C12. Transmucosal electrical resistance was extensively decreased by C12, indicating that C12 could enhance the drug absorption at least partly by expanding the paracellular route. L-Gln significantly, but not completely, recovered resistance lowered by C12. Electrical potential difference was markedly reduced by C12, suggesting that C12 lowered the viability of mucosal cells, but 10 mM L-Gln significantly recovered potential difference almost to the control level. These results suggested the possibility that absorption-enhancing formulation with low local toxicity, which is low enough to be used practically, could be developed by using an amino acid like L-Gln as an ingredient attenuating the local toxicity caused by C12.

Amino Acids↗

Indicators of rapid clinical recovery in Guillain-Barré syndrome.

To elucidate the features of patients with Guillain-Barré syndrome who show markedly rapid clinical recovery, clinical, serological, and electrophysiological data of 80 consecutive patients were reviewed. Antigangliosides, and Campylobacter jejuni and Haemophilus influenzae antibodies were measured by enzyme linked immunosorbent assays. Nine (11%) patients showed rapid recovery (improvement by two or more Hughes grades within 2 weeks). They often had electrodiagnosis of acute motor axonal neuropathy (AMAN; 67%), preserved tendon reflexes (44%), anti-GM1 antibodies (89%), preceding H influenzae infection (44%), and received immunoglobulin treatment (44%). On the other hand six patients with poor prognosis often had AMAN (100%) and anti-GM1 antibody (83%), but a higher incidence of preceding C jejuni infection (83%). It is concluded that patients with Guillain-Barré syndrome with AMAN and anti-GM1 antibodies have either faster or slower recoveries. Among the axonal subgroup of patients with Guillain-Barré syndrome, preserved tendon reflexes, H influenzae infection, and the patient having received immunoglobulin treatment may be indicators of rapid recovery.

Adolescent↗

"Tactile" sensory nerve potentials elicited by air-puff stimulation: a microneurographic study.

To investigate the sensory nerve responses to selective touch stimulation, sensory nerve action potentials after brief air-puffs were recorded with a microelectrode. In patients with peripheral neuropathy, those with impairment of tactile sensations had significantly smaller responses than did those without tactile impairment, suggesting receptor activation failure as well as nerve conduction failure. Brief air-puff stimulation, when combined with microneurography, could be used for evaluating the tactile receptor properties in humans.

Adult↗