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Biomedical subjects

S Kuwabara

Publications and source records attributed to S Kuwabara.

At least 37 records · Page 2Linked to original sources

Anti-GM1 antibody IgG subclass: a clinical recovery predictor in Guillain-Barré syndrome.

OBJECTIVE: To determine whether the anti-GM1 antibody IgG subclass (IgG1 to 4) is associated with clinical profiles and patterns of recovery in Guillain-Barré syndrome (GBS). METHODS: The IgG subclassification of anti-GM1 antibody was examined and compared with clinical data on 42 GBS patients positive for the antibody. RESULTS: Frequent anti-GM1 antibody subclasses were IgG1 (76%) and IgG3 (31%). IgG1 antibody was associated with preceding gastroenteritis and Campylobacter jejuni serology, whereas IgG3 antibody was associated with preceding respiratory infection. Although the severity at nadir was similar for IgG1- and IgG3-positive patients, the percentage of patients who could not walk independently was greater for the IgG1-positive group 1 month (42 vs 0%; p = 0.02), 3 months (28 vs 0%), and 6 months (25 vs 0%) after onset. Rapid recovery within 1 month occurred frequently in the patients with the IgG3 antibody but rarely in those with the IgG1 antibody (67 vs 11%; p = 0.003). CONCLUSIONS: The IgG1 subclass of anti-GM1 antibody is a major subtype indicative of slow recovery, whereas isolated elevation of IgG3 subclass antibody titer suggests rapid recovery. Variation in subclass patterns may depend on which pathogen precipitates GBS.

Adult↗

[Showing no increase of C-reactive protein and developing non-bacterial median chest wound dehiscence after coronary artery bypass grafting].

A 72-year-old male underwent coronary artery bypass grafting for 3 vessels disease. After the operation, the peak C-reactive protein (CRP) level was 0.85 mg/dl and CRP levels stayed very low. Forty days after the operation the patient developed a progressive median chest wound dehiscence but the bacterial cultures were negative. In spite of conventional therapies such as debridement of necrotic tissue or irrigation, the wound granulation was underdeveloped. After 6 months an epidermis had developed to cover the wound.

Aged↗

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↗

Autonomic function in demyelinating and axonal subtypes of Guillain-Barré syndrome.

OBJECTIVES: To investigate whether or not the pattern and extent of autonomic involvement differ between the two subtypes of Guillain-Barré syndrome (GBS), namely acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). METHODS: Head-up tilt test, R-R interval variation, plasma noradrenaline concentration, skin vasomotor reflex (SVR) and sympathetic sweat response (SSwR) were used to estimate autonomic function in seven AIDP and eight AMAN patients. RESULTS: Heart rate and plasma noradrenaline concentration were significantly high in the AIDP group but not in the AMAN group. Skin vasomotor reflexes were generally preserved and SSwRs were impaired in patients with severe neurological deficits for both AIDP and AMAN groups. CONCLUSION: The patterns of autonomic involvement are qualitatively different between AIDP and AMAN. Acute inflammatory demyelinating polyneuropathy is characterized by cardio-sympathetic hyperactivity, excessive or reduced sudomotor function and preserved skin vasomotor function, while AMAN is not necessarily generally associated with marked autonomic dysfunction except for the sudomotor hypofunction seen in patients with severe neurological deficits.

Adult↗

Significance of immunohistochemical nodal micrometastasis as a prognostic indicator in potentially curable oesophageal carcinoma.

BACKGROUND: The number of positive lymph nodes is an important prognostic predictor in patients with oesophageal cancer. However, the significance of nodal micrometastasis in patients with overt nodal metastasis is unknown. The aim of this study was to clarify the clinical implications of nodal micrometastasis in patients undergoing curative oesophagectomy for oesophageal cancer. METHODS: Cervical, mediastinal and abdominal lymph nodes systematically removed from 104 patients with oesophageal cancer were examined immunohistochemically to detect cells that stained positively for cytokeratins with the monoclonal antibody cocktail AE1/AE3. The postoperative course and survival rates were compared among patients with and without micrometastases, after numerical classification of overt metastatic nodes (none, between one and four, five or more). RESULTS: Univariate analysis showed T stage, nodal micrometastasis and number of overt nodal metastases to be significant prognostic factors after oesophagectomy. Multivariate analysis revealed nodal micrometastasis and number of overt nodal metastases to be independent prognostic factors. The presence of micrometastases had a significant adverse effect on postoperative survival in patients with no overt metastasis and in patients with one to four overt metastatic nodes, but no such impact in patients with five or more overt metastatic nodes. CONCLUSION: Assessment of nodal status by both histological examination for overt metastases and immunohistochemical examination for micrometastases is useful in stratifying patients undergoing curative oesophagectomy.

Adult↗

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↗

Clinical features and prognosis of Miller Fisher syndrome.

The authors reviewed the clinical features and outcome of Miller Fisher syndrome (MFS) for 50 consecutive patients with MFS including 28 patients who received no immunotherapy. Besides the characteristic clinical triad (ophthalmoplegia, ataxia, and areflexia), pupillary abnormalities, blepharoptosis, and facial palsy are frequent in MFS, whereas sensory loss is unusual despite the presence of profound ataxia. Patients with MFS usually had good recovery and no residual deficits.

Adolescent↗

Serum levels of tumor necrosis factor-alpha in chronic inflammatory demyelinating polyneuropathy.

BACKGROUND: Activated macrophages and T lymphocytes may play a role in the pathogenesis of chronic inflammatory demyelinating polyneuropathy (CIDP). Both cell types secrete tumor necrosis factor-alpha (TNFalpha), which has toxic effects on myelin and endothelial cells. METHODS: The serum concentration of TNFalpha was measured by ELISA and compared with clinical and electrophysiological profiles in 20 patients with CIDP. RESULTS: An increased serum level of TNFalpha was detected in 5 (25%) patients and was associated with subacute progression, severe neurologic disabilities, and symmetric weakness involving proximal as well as distal muscles. TNFalpha levels increased during the active phase in this subgroup of patients. The levels of TNFalpha correlated with the severity of demyelinating conduction abnormalities in the intermediate as well as distal nerve segments, suggesting demyelination diffusely distributed along the nerves. CONCLUSION: Circulating TNFalpha increases during the active phase in a subgroup of CIDP patients and may play a role in the pathogenesis of demyelination and the breakdown of the blood-nerve barrier in CIDP.

Adolescent↗

Voluntary contraction impairs the refractory period of transmission in healthy human axons.

1. Voluntary contraction of a muscle causes substantial hyperpolarization of the active motor axons due to activation of the electrogenic Na+-K+ pump. The present study was undertaken to determine whether voluntary effort produces a significant impairment in impulse transmission in normal axons and whether mechanisms other than membrane hyperpolarization contribute to the changes in axonal excitability. 2. The compound muscle action potential (CMAP) was recorded after median nerve stimulation at the wrist using sub- and supramaximal stimuli, delivered singly and in pairs at conditioning-test intervals of 2-15 ms. Axonal excitability parameters (threshold, refractoriness, supernormality, and strength-duration time constant (tauSD)) were measured using threshold tracking. Impulse transmission was assessed using supramaximal stimuli. 3. Maximal voluntary contractions of the abductor pollicis brevis for 1 min produced a substantial increase in threshold, an increase in supernormality and a decrease in tauSD, all of which lasted approximately 10 min and indicate axonal hyperpolarization. However, immediately after the contraction there was an unexpected increase in refractoriness. The post-contraction increase in refractoriness could not be mimicked by an imposed ramp of hyperpolarization that produced changes in the other indices to an extent that was similar to voluntary contraction. 4. The contraction had relatively little effect on the size of the unconditioned maximal CMAP. However, there was failure of transmission of supramaximal conditioned volleys when the conditioning-test interval was short. 5. The relationships between axonal excitability and supernormality and tauSD following voluntary contraction differed significantly from those recorded during the hyperpolarization produced by DC current. It is argued that these differences probably result from extra-axonal K+ accumulation with the voluntary contraction but not with the DC polarization. I6. It is concluded that, following maximal voluntary contraction of a normal muscle, the refractory period of transmission is impaired distal to the stimulus site sufficient to cause transmission failure of the second of a pair of closely spaced impulses. The site of transmission failure is likely to be the terminal axon, presumably at branch points, possibly in the unmyelinated pre-terminal segment.

Action Potentials↗

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↗

Differences in responses of cutaneous afferents in the human median and sural nerves to ischemia.

Recent evidence suggests that two conductances responsible for accommodation to changes in membrane potential (a slow K(+) conductance and inward rectification [I(H)]) are less active on cutaneous afferents in the sural nerve than on those in the median nerve, and it has been suggested that these axons would therefore respond differently to stress, whether natural or due to disease. The present study was undertaken in eight healthy volunteers to determine whether these afferents respond differently to the depolarizing and hyperpolarizing stresses that accompany ischemia for 13 min and subsequent recovery. During ischemia, the decrease in threshold was quantitatively less for the sural afferents, as were the changes in the other indices of axonal excitability, presumably because the ischemic depolarization was less for sural afferents. Following release of ischemia, there was, as predicted, a divergence in the pattern of threshold change. With median afferents there was evidence of a transient depolarization, believed to be due to inward rectification, superimposed on a long-lasting hyperpolarization. The response of sural afferents lacked this transient depolarizing threshold change. Cutaneous afferents in the median and sural nerves behave differently in response to ischemic and postischemic stresses, and it is likely that they will also respond differently to disease processes. In a number of respects the differences between sural and median afferents are analogous to differences between diabetic and normal nerves.

Humans↗

Tumor angiogenesis as an independent prognostic factor after extended radical esophagectomy for invasive squamous cell carcinoma of the esophagus.

BACKGROUND: Currently, there is only limited information regarding tumor angiogenesis and its clinical implications in cases of esophageal carcinoma. The purpose of this study was to clarify which clinicopathologic parameters correlate with tumor angiogenesis; furthermore, the study was conducted to evaluate whether tumor angiogenesis is an independent prognostic factor in cases of esophageal carcinoma. METHODS: Intratumoral microvessel density (MVD) and thymidine phosphorylase (dThdPase) expression were immunohistochemically studied after extended radical esophagectomy in 103 cases of esophageal carcinoma. RESULTS: Increased MVD significantly correlated with the depth of tumor invasion, the frequency of intramural metastasis, and the stage of tumor advancement (P <.05). dThdPase expression status significantly correlated with the size and depth of primary tumors (P <.02). A significant correlation was present between MVD and the expression status of dThdPase (P <.01). Furthermore, increased MVD correlated with increased tumor recurrence after esophagectomy and with poorer survival curves (P <.01 and P <.05, respectively). A multivariate analysis revealed MVD to be an independent predictor of unfavorable prognosis. CONCLUSIONS: Tumor angiogenesis expressed as MVD correlates with clinicopathologic parameters regarding tumor progression and is an independent prognostic indicator in patients undergoing extended radical esophagectomy for invasive esophageal carcinoma.

Adult↗

Membrane properties in chronic inflammatory demyelinating polyneuropathy.

Threshold tracking was used to compare excitability properties (stimulus-response curves, strength-duration properties, recovery cycle and threshold electrotonus) of the median nerve in 11 patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and 25 healthy controls. Stimulus-response curves were significantly different: threshold was much higher, the slope of the curves reduced and the spread of the thresholds greater in the CIDP group. The strength-duration time constant (tau(SD)) was significantly shorter and the rheobase higher in the CIDP group. In the recovery cycle, the CIDP group had less refractoriness, supernormality and late subnormality than healthy controls, but the duration of the relatively refractory period was normal. These changes in tau(SD) and the recovery cycle were not those previously predicted. There were no consistent changes in threshold electrotonus, suggesting that, for the studied axons, there are no consistent changes in accommodation properties that depend on internodal conductances. It is difficult to explain these changes in excitability on the basis of a change in membrane potential, or solely as the result of demyelination, and it is possible that other morphological factors such as variable remyelination and inflammatory oedema affected axonal excitability in the patients.

Action Potentials↗

Differences in accommodative properties of median and peroneal motor axons.

OBJECTIVES: To investigate whether accommodation to depolarising and hyperpolarising currents differs for motor axons of human upper and lower limb nerves. METHODS: The threshold tracking technique was used to measure threshold electrotonus for median and peroneal motor axons. The threshold current that produced a compound muscle action potential 50% of maximum was measured, and membrane potential was altered using subthreshold polarising currents of 330 ms duration but of variable intensity, from +40% (depolarising) to -100% (hyperpolarising) of the unconditioned threshold. RESULTS: The maximal threshold changes (the peak of the S1 phase of threshold electrotonus) were significantly greater in median axons for both depolarising and hyperpolarising currents. The subsequent phases of accommodation to depolarising currents (S2) and to hyperpolarising currents (S3) were also significantly greater in median axons. These findings raised the possibility that greater accommodation (S2 and S3) in median axons resulted from greater changes in membrane potential. However, regression of S2 against S1 to depolarising currents disclosed significantly greater accommodation (27.8%) for median axons, suggesting that slow K(+) conductances may be more prominent on median than peroneal axons. By contrast, the relation between S3 and S1 to hyperpolarising currents was similar for the two nerves, suggesting that the difference in inward rectification was merely because the conductance varies with the extent of hyperpolarisation. CONCLUSIONS: Slow K(+) conductances are more prominent for median motor axons than for peroneal axons. It would therefore be expected that axons innervating the lower limbs have less protection from depolarising stress and could develop ectopic activity more readily.

Action Potentials↗

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↗