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Biomedical subjects

Tony Wu

Publications and source records attributed to Tony Wu.

10 recordsLinked to original sources

Prospective randomized trial comparing shock wave lithotripsy and ureteroscopic lithotripsy for management of large upper third ureteral stones.

OBJECTIVES: To conduct a prospective and randomized trial to compare the efficiency quotient and cost-effectiveness index of shock wave lithotripsy (SWL) and ureteroscopic lithotripsy (URSL) for the treatment of large upper third ureteral stones. METHODS: A total of 35 male patients and 7 female patients with a solitary, radiopaque upper ureteral stone, 15 mm or more in diameter, who underwent SWL or URSL were enrolled in this study. The mean patient age was 53.1 +/- 14.5 years. The endpoint of the study was for the patient to be stone free or to have insignificant residual stone (3 mm or less) within the kidney. RESULTS: The mean stone length +/- SD was 17.9 +/- 3.9 cm in the SWL group and 18.5 +/- 2.9 cm in the URSL group (P > 0.05). The efficiency quotient for SWL and URSL was 0.61 and 0.63, respectively. The cost-effectiveness index, treatment time, pain score, and hospital stay were greater in the URSL group. However, the degree of hydronephrosis significantly influenced the success rate of SWL. All patients with severe hydronephrosis in the SWL group needed auxiliary surgical procedures to become stone free. CONCLUSIONS: The efficiency quotients of SWL and URSL were comparable in the treatment of large upper third ureteral stones. However, SWL should not be recommended as the first-line treatment option for the management of upper third ureteral stones larger than 1.5 cm with severe hydronephrosis. Understanding the cost-effectiveness, success rate, pain score, and patient satisfaction score for the two different approaches constitutes the indispensable requisites for choosing the optimal first-line therapeutic strategy.

Cost-Benefit Analysis↗

Contact heat evoked potentials in normal subjects.

Laser-evoked potentials are widely used to investigate nociceptive pathways. The newly developed contact heat stimulator for evoking brain response has the advantages of obtaining reliable scalp potentials and absence of cutaneous lesions. This study aimed to identify the most appropriate stimulation site with consistent cortical responses, and to correlate several parameters of the contact heat evoked potentials (CHEPs) with age, gender, and body height in normal subjects. CHEPs were recorded at Cz with a contact heat stimulator (Medoc, Israel) in 35 normal controls. The subjects were asked to keep eyes open and remain alert. The baseline temperature was 32 degrees C, and stimulation peak heat intensity of 51 degrees C was applied to five body sites: bilateral forearm, right dorsum hand, right peroneal area, and right dorsum foot. Reproducible CHEPs were recorded more frequently when stimulated at volar forearm (62.5%) than at the lower limbs (around 40%). The first negative peak latency (N1) was 370.1 +/- 20.3 ms, first positive peak latency (P1) was 502.4 +/- 33.0 ms, and peak to peak amplitude was 10.2 +/- 4.9 microV with stimulation of the forearm. Perceived pain intensity was not correlated with the presence or amplitude of CHEPs. No gender or inter-side differences were observed for N1 latency and N1-P1 amplitude. Also, no correlation was noted between N1 and age or body height. These results support future clinical access of CHEPs as a diagnostic tool.

Adolescent↗

Autonomic dysfunction in Machado-Joseph disease.

OBJECTIVE: Machado-Joseph disease is an autosomal dominant spinocerebellar ataxia with expanded trinucleotide repeats. Although autonomic nervous system degeneration was documented in postmortem reports, the autonomic dysfunction in patients with Machado-Joseph disease, either in clinical analysis or electrophysiological investigations, has not yet been studied in detail. METHODS: Fifteen patients with genetically confirmed Machado-Joseph disease and 34 healthy subjects were studied. The study design included a detailed questionnaire, R-R interval variation on deep breathing or Valsalva maneuver, and sympathetic skin response evoked by electrical stimulation of the median nerve or magnetic stimulation of the neck. RESULTS: Sixty-seven percent of patients had at least 3 symptoms involving different aspects of autonomic functions. Voiding problems and thermoregulatory disturbance were the most common symptoms. Ten (71%) of 14 patients had abnormal R-R interval variation with a significant reduction of the mean ratio. Prolonged latency or absence of sympathetic skin response to electrical stimulation was identified in 73% of patients and to magnetic stimulation, in 53%. R-R interval variation and sympathetic skin response showed good correlation with the functional stage. Electrical stimulation revealed the highest sensitivity, specificity, and positive predictive value compared with other tests. CONCLUSION: The present investigation documents that autonomic dysfunction is not uncommon in patients with Machado-Joseph disease and might be related to the clinical progression.

Adult↗

Pallidotomy effect on the cortical excitability in patients with severe Parkinson's disease.

Surgical lesions in the medial pallidum have been shown to ameliorate motor deficits in patients with Parkinson's disease (PD). It is believed that interruption of the pallidothalamocortical projections to the motor cortex is required for the satisfactory results. In this report, we adopt cortico-cortical inhibition as the tool to assess the pallidotomy effect on cortical excitability in PD. Interstimulus interval between 1 and 15 msec were investigated. The average peak-to-peak amplitude was measured and calculated at each delay. A total of 8 patients (M:F = 4:4) 54.9 years of age (SD = 9.6) and 10 controls were recruited for the study. In the controls, the inhibitory phenomenon was observed from the 1-msec to the 4-msec delay points and the maximal inhibition was at the 3-msec delay point (33.69% +/- 6.50% of the control response). Mild facilitation was noticed since the 5-msec delay point and thereafter. In patients before operation, a similar trend of inhibition was also observed in the initial 4 msec with the maximal inhibition also at the 3-msec delay point (64.66 +/- 6.77% of the control response). In the postoperative group, the short interstimulus interval inhibition can no longer be observed and the conditioned response was 95.06 +/- 23.68% of the control at the 3-msec delay point. The suppression was gone at and after the 7-msec delay point. Results of repeated-measures analysis of variance show a significant difference among the controls and PD patients before and 3 months after pallidotomy (F = 3.40, P = 0.05). Post hoc examination revealed a significant difference between the controls and PD patients 3 months after pallidotomy at the 3-msec delay point (P = 0.004). However, no correlation was observed between the 3-msec inhibition and the Unified Parkinson's Disease Rating Scale Motor score or the dyskinesia score. The results suggest that pallidotomy can modulate the cortical inhibitory circuitry in patients with PD.

Adult↗

Glutamate transporter function of rat hippocampal astrocytes is impaired following the global ischemia.

Astroglial glutamate transporters, GLT-1 and GLAST, play an essential role in removing released glutamate from the extracellular space and are essential for maintaining a low concentration of extracellular glutamate in the brain. It was hypothesized that impaired function of glial glutamate transporters induced by transient global ischemia may lead to an elevated level of extracellular glutamate and subsequent excitotoxic neuronal death. To test this hypothesis, in the present study, we performed whole-cell patch-clamp recording of hippocampal CA1 astrocytes in control or postischemic slices, and measured glutamate transporter activity by recording glutamate-evoked transporter currents. Six to 24 h after global ischemia, maximal amplitude of glutamate transporter currents recorded from postischemic CA1 astrocytes was significantly reduced. Western blotting analysis indicated that transient global ischemia decreased the protein level of GLT-1 in the hippocampal CA1 area without affecting GLAST protein level. Further real-time quantitative RT-PCR assays showed that global ischemia resulted in a decrease in GLT-1 mRNA level of hippocampal CA1 region. Global ischemia-induced reduction in GLT-1 expression and glutamate transporter function of CA1 astrocytes precedes the initiation of delayed neuronal death in CA1 pyramidal layer. The present study provides the evidence that transient global ischemia downregulates glutamate transporter function of hippocampal CA1 astrocytes by decreasing mRNA and protein levels of GLT-1.

Amino Acid Transport System X-AG↗

Down-regulation of the glial glutamate transporter GLT-1 in rat hippocampus and striatum and its modulation by a group III metabotropic glutamate receptor antagonist following transient global forebrain ischemia.

Our goals were to identify biochemical markers for transient global ischemia-induced delayed neuronal death and test possible drug therapies against this neuronal damage. Four-vessel occlusion (4-VO) for 20 min was used as a rat model. The temporal expression profiles of three glutamate transporters (GLT-1, GLAST and EAAC1) were evaluated in the CA1 region of the hippocampus and the striatum. The protein levels of the GLT-1 were significantly down-regulated between 3 and 6 h after ischemia-reperfusion in the CA1 region and striatum, returned to the control (2-VO) levels 24 h after reperfusion and remained unchanged for up to 7 days. The levels of GLAST in the CA1 region and striatum, and EAAC1 in the CA1 region did not change after ischemia from 1 h to 7 days. Pretreatment with group III metabotropic glutamate receptor antagonist s-alpha-MCPA (20 microg/5 microl) 30 min prior to 4-VO significantly restored the GLT-1 levels in the CA1 region caused by global ischemia at both 3 and 6 h after reperfusion. The loss of pyramidal neurons in the CA1 region due to ischemia-reperfusion could also be prevented by intraventricular pretreatment with s-alpha-MCPA. The current findings pinpoint the significance of GLT-1 during ischemia/reperfusion and suggest a potential application of group III metabotropic glutamate receptor antagonist against ischemic/hypoxic neuronal damage.

2-Methyl-4-chlorophenoxyacetic Acid↗

Functional analysis of connexin-32 mutants associated with X-linked dominant Charcot-Marie-Tooth disease.

To investigate the pathogenic role of connexin-32 (Cx32) mutation in X-linked dominant Charcot-Marie-Tooth disease (CMTX), dual whole-cell voltage-clamp recordings and tracer coupling were performed to investigate functional properties of wild-type and 22 CMTX mutant Cx32 proteins expressed in N2A cells. Ten mutant Cx32 proteins either formed defective junctional channels (Y65C, V95M, R107W, L156R, R164W and G199R) or failed to form gap junctions (G12S, S182T, E208K and Y211stop). Except (G12S) and (E208K) mutants, other mutant Cx32 proteins were localized in the cell membrane despite their impaired ability to form functional gap junctions. Twelve CMTX mutations (V13L, R15Q, R22Q, I30N, V35M, V63I, R75Q, Q80R, W133R, P158A, P172S and N205S) did not affect the ability of Cx32 to form homotypic gap junctions in N2A cells. Our results indicate that 10 of 22 CMTX Cx32 mutations studied in the present investigation could lead to the assembly of defective Cx32 gap junctions, which in turn may result in peripheral neuropathy. However, further studies are required to elucidate the exact mechanism by which CMTX mutant Cx32 proteins, which retain the ability to form homotypic junctional channels, damage Schwann cells and cause demyelinating neuropathy.

Amino Acid Substitution↗

Clinical and electrophysiological studies of a family with probable X-linked dominant Charcot-Marie-Tooth neuropathy and ptosis.

BACKGROUND: The X-linked dominant Charcot-Marie-Tooth neuropathy (CMTX) is a hereditary motor and sensory neuropathy linked to a variety of mutations in the connexin32 (Cx32) gene. Clinical and genetic features of CMTX have not previously been reported in Taiwanese. METHODS: Clinical evaluations and electrophysiological studies were carried out on 25 family members of a Taiwanese family group. Molecular genetic analysis of the Cx32 gene was performed. A sural nerve biopsy was obtained from 1 patient. RESULTS: Nine patients had clinical features of X-linked dominant inheritance and a moderate Charcot-Marie-Tooth (CMT) neuropathy phenotype. Molecular genetic analysis showed no mutation of the Cx32 coding region, but revealed a G-to-A transition at position -215 of the nerve-specific promoter P2 of the Cx32 gene. Ptosis is 1 clinical manifestation of neuropathy in this probable CMTX family. Familial hyperthyroidism is an additional independent feature of the family. Electrophysiological and histological studies showed features of axonal neuropathy. Multimodality evoked potential studies revealed normal central motor and sensory conduction velocities. CONCLUSIONS: The presence of ptosis in this family illustrates the existence of clinical heterogeneity among related family members with CMTX similar to that in CMT of autosomal inheritance. Electrophysiological and histological findings revealed normal central conduction and axonal neuropathy.

Acute Disease↗

Short-term effect of bilateral subthalamic stimulation for advanced Parkinson's disease.

BACKGROUND: Subthalamic nucleus (STN) hyperactivity is a pathophysiological phenomenon of Parkinson's disease (PD). Inhibition of this hyperactivity by chronic deep brain stimulation (DBS) can possibly reset the aberrant function of the cortico-striato-thalamal circuit and improve the parkinsonian symptoms. DBS was introduced as a safe and alternative way of performing functional stereotaxic surgery for treating PD. METHODS: Seven advanced PD patients with complicated motor fluctuations and dyskinesia were enrolled in the study. A quadripolar electrode was bilaterally installed in the STN. Patients were evaluated before and 6 months after implantation using a battery of clinical assessments, including the motor score of the unified Parkinson's disease rating scale (UPDRS), modified Hoehn and Yahr (HY) staging, and the Schwab and England activities of daily living scale (SEADL). Preoperative baseline evaluations included both "off-medication" periods and "on-medication" periods, while postoperative evaluations included a cross-over of the above 2 periods with and without DBS. RESULTS: The motor disability, HY staging, and SEADL all significantly improved in both the off- and on-medication periods 6 months after STN DBS. Compared to the baseline off-medication score, a significant improvement was found in the UPDRS motor and other subscores including tremors, rigidity, and bradykinesia. The SEADL score showed a great improvement of 205.6%. Ballism/chorea, mood changes, and blepharospasm may have been induced by DBS. Neither serious nor permanent side effects appeared. CONCLUSIONS: Bilateral STN DBS improved the motor symptoms in advanced PD patients in both the off- and on-medication periods. They showed improvements not only in motor disabilities of tremors, rigidity, bradykinesia, and postural and gait instability, but also in levodopa-related dyskinesia and psychosis.

Aged↗

Hemiballism after subthalamotomy in patients with Parkinson's disease: report of 2 cases.

The occurrence of persistent hemiballism after subthalamotomy for Parkinson's disease (PD) has not been described as frequently as mild or transient dyskinesia. We report on 2 patients with advanced PD who developed hemiballism and/or dyskinesia after subthalamotomy. One patient with a small lesion confined to the subthalamic nucleus (STN) developed persistent hemiballism; the other with a larger lesion involving the STN and also the zona incerta presented with a transient dyskinesia in a single limb. We conclude that a precise STN lesion might bear a potential risk of persistent hemiballism.

Chorea↗