Biomedical subjects
Publications and source records attributed to Y L Lo.
Ptosis is known to be associated with thyroid disorders. We describe two biochemically corrected hypothyroid patients presenting with isolated bilateral ptosis. EMG of the orbicularis oculi showed continuous grouped motor unit potentials. In the absence of obvious aetiology, it is hypothesised that focal demyelination of terminal branches to the orbicularis oculi may play a role in the generation of the discharges.
OBJECTIVE: To investigate repetitive stimulation of the long thoracic nerve as a reliable and technically undemanding method for evaluating respiratory muscle function in myasthenia gravis. METHODS: 15 patients with myasthenia gravis and positive single fibre electromyography had repetitive stimulation of the long thoracic nerve together with serratus anterior recordings. There were 20 normal controls. RESULTS: Eight patients with respiratory symptoms all had abnormal results, with an increased response decrement. These patients required intensive monitoring and supplemental oxygen. The remaining seven cases with no respiratory symptoms all had negative studies. CONCLUSIONS: This is a simple well tolerated method that shows good correlation with respiratory symptoms and management requirements in myasthenia gravis. It can alert the physician to serious respiratory complications in this disease.
The electrodiagnosis of peripheral neuropathy is often based on nerve conduction abnormalities in sensory nerves of the lower extremities. We performed nerve conduction studies of the deep peroneal sensory nerve prospectively in 63 limbs of 38 normal subjects. The sensory amplitudes showed a decreasing trend with increasing age. 21% of subjects had absent sensory potentials, especially those in the older age groups. This was seen in contrast with superficial peroneal and sural potentials, which were universally present. Although the deep peroneal sensory nerve is located in the distal lower limb, it should be used with caution in evaluating peripheral neuropathy, in view of the frequent occurrence of absent potentials even in asymptomatic normal subjects.
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A 48-year-old man presented with painless left trapezius hypertrophy 20 years after radiotherapy for nasopharyngeal carcinoma. EMG sampling showed myokymic discharges, reduced polyphasic motor unit recruitment and no signs of active denervation. The relationship between radiotherapy, brachial plexopathy and neurogenic muscle hypertrophy is discussed.
OBJECTIVES: To assess the diagnostic efficacy of repetitive nerve stimulation (RNS) of the hypoglossal nerve in patients with myasthenia gravis (MG) and bulbar symptoms (dysphagia, dysarthria). METHODS: Twenty patients with MG and 25 normal controls had RNS of the hypoglossal nerve. All patients also had single fibre electromyography (SFEMG) of the orbicularis oculi and RNS with recordings of the nasalis, trapezius and abductor pollicis brevis muscles. RESULTS: All patients had positive SFEMG studies. Nine patients with bulbar symptoms had positive hypoglossal RNS, including 3 with negative RNS recordings in other muscles. Eleven patients with no bulbar symptoms showed negative hypoglossal RNS, including two with positive RNS recordings from other muscles. CONCLUSIONS: Abnormal RNS of the hypoglossal nerve correlates well with bulbar dysfunction and further characterises the extent of neuromuscular transmission defect in MG patients.
We describe here two cases of Cryptococcus neoformans var. gattii meningitis that occurred in Singapore. This variety of Cryptococcus neoformans differs from the more widely known C. n. var. neoformans in its ecology and epidemiology. Infections with this variety are still rare in Singapore.
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Botulinum toxin (BTX) has been used successfully to treat various movement disorders, and is increasingly used for many other medical conditions. Sialorrhoea is a disabling symptom in many neurological patients including those with Parkinson's disease, stroke and amyotrophic lateral sclerosis (ALS). BTX has recently been shown to be effective for treating sialorrhoea. We report an ALS patient who developed recurrent jaw dislocation following BTX treatment for sialorrhoea to highlight the observation that intraparotid BTX may be complicated by jaw dislocations in some at-risk ALS patients. Clinicians using BTX to treat sialorrhoea in ALS need to be aware of this potentially serious complication.
Conventional nerve conduction and electromyography may not be adequate in localizing ulnar neuropathy at the elbow, particularly in longstanding lesions with severe axon loss. Ratios of wrist to elbow and elbow to axilla segmental ulnar mixed nerve amplitudes were determined in 11 patients with ulnar neuropathy at the elbow. In 20 control subjects, the mean ratio was 1.06 +/- 0.25 (standard deviation). All patients had ratios less than two standard deviations of the control mean ratio. This method is a useful adjunct to conventional nerve conduction techniques in the localization of ulnar neuropathy at the elbow.
OBJECTIVES: To evaluate serial central motor conduction time in the Miller Fisher syndrome. METHOD: Three patients with classic Miller Fisher syndrome were evaluated clinically. They had serial central motor conduction times measured with transcranial magnetic stimulation and nerve conduction studies. Motor evoked potentials were recorded from the first dorsal interossei and abductor hallucis muscles. RESULTS: All three patients showed reduction in central motor conduction times in tandem with gradual clinical improvement at each review. CONCLUSIONS: There is electrophysiological evidence of a central reversible corticospinal tract conduction abnormality in the Miller Fisher syndrome.
BACKGROUND: The aims of this study were (a) to establish normative data of thermal symmetry (left vs. right) in normal subjects; (b) to compare the skin temperature in various regions between young and old people in Taiwan and between male and female. METHODS: The skin surface of 57 healthy volunteers (aged 24 to 80 yr) was divided into 25 areas and measured by an infrared thermography (Avionics TVS-2000, Japan). The average temperatures of these 25 regions were compared: (a) left vs. right side, (b) young (< or = 60 yr, n = 37) vs. old (> 60 yr, n = 20), and (c) male vs. female. Student's t-test was used to assess means between both groups. RESULTS: The neck carried the highest skin temperature (31.9 degrees C +/- 0.6; mean +/- SD) of the body in comparison with the toes that had the lowest one (27.5 degrees C +/- 2.0). The side-to-side temperature differences were subtle, which did not exceed 0.5 degrees C. The average skin temperature of elderly was slightly lower than that of young subjects in 11 out of 25 areas (p < 0.05), especially the distal parts of extremities. Elderly female had lower skin temperature in various truncal areas as compared with their counterpart. However, the skin temperature was higher in the distal extremity (p < 0.05). CONCLUSIONS: The thermoregulatory system is substantially symmetrical. The result of this study offered valuable normative database on skin thermal symmetry in normal population of Taiwan, and may be useful as a diagnostic aid in patients with various states of disorders associated with autonomic dysfunctions.
Phospholipids have been increasingly used as carriers for the delivery of a variety of drugs. Studies using cancer chemotherapeutic agents such as epirubicin encapsulated in liposomes, which are made of phospholipids and other ingredients, have generally shown reduced toxicity and enhanced therapeutic efficacy. The recent investigation of the role of P-glycoprotein (P-gp) in phospholipid translocation has opened a new area of research on the possible use of phospholipids as multidrug resistance (MDR) modulators. This study investigated the effects of liposomal encapsulation, empty liposome pretreatment, or free lipid pretreatment on the uptake and transport of epirubicin in the human colon adenocarcinoma cell line Caco-2 and in everted gut sacs of rat jejunum and ileum. Epirubicin uptake experiments, using a flow cytometer, showed that both liposomal encapsulation and empty liposome pretreatment increased the intracellular accumulation of epirubicin in Caco-2 cells significantly. These two treatments substantially increased apical-to-basolateral absorption of epirubicin across Caco-2 monolayers and markedly improved mucosal-to-serosal absorption of epirubicin in rat jejunum and ileum. Enhancement also was observed with both liposome encapsulation and empty liposome pretreatment in the reduction of basolateral-to-apical efflux of epirubicin across Caco-2 monolayers. However, because diffusion of free dipalmitoyl phosphatidylcholine (DPPC) or dipalmitoyl phosphatidylethanolamine (DPPE) lipids across the cell membrane is very slow, these free lipids showed marginal effects on absorption and/or secretion of epirubicin in both Caco-2 cells and rat gut sacs. The study suggests that inhibition of P-gp or other transporter proteins located in the intestines may be partially involved in the reduction of epirubicin efflux. In conclusion, the therapeutic efficacy of epirubicin may be improved by using phospholipids as excipients and MDR modulators in the formulations. Liposomal formulations may have important applications to circumvent drug resistance in cancer chemotherapy.
Breast cancer is considered to display a high degree of intratumor heterogeneity, without any obvious morphological and pathological steps to define sequential evolution, and its progression may vary among individual tumors. In an attempt to elucidate these etiological and phenotypic complexities, the present study, based on the fundamental concept that genomic instability is the engine of both tumor progression and tumor heterogeneity, was conducted to test the hypothesis that breast cancer pathogenesis is driven by double-strand break (DSB)-initiated chromosome instability (CIN). The rationale underlying this hypothesis is derived from the clues provided by family breast cancer syndromes, in which susceptibility genes, including p53, ATM, BRCA1 and BRCA2, are involved within the common functional pathway of DSB-related checkpoint/ repair. Because genomic deletion caused by DSB is reflected in the genetic mechanism of loss of heterozygosity (LOH), this genome-wide LOH study was conducted, using 100 tumors and 400 microsatellite markers. To minimize the effect of heterogeneity within tumors, the experimental technique of laser capture microdissection was used to ensure that genetic and phenotypic examinations were based on the same tumor cells. Support for our hypothesis comes from the observations that: (a) the extent of DSB-initiated CIN in tumors significantly increased as tumors progressed to poorer grades or later stages; (b) in the sequential steps toward CIN, the loci of p53 and ATM, the key checkpoint genes against DSB, were lost at the earliest stage; and (c) many loci identified to be important in breast tumorigenesis were the genomic sites possibly harboring the genes involved in DSB-related checkpoint/repair (including RAD51, RAD52, and BRCA1) or CIN (including FA-A, FA-D, and WRN), and a higher number of these loci showing LOH was significantly associated with increased level of DSB-initiated CIN (P < 0.0001). Breast cancers are thus considered to be sequentially progressive with CIN. However, CIN might also cause genetic heterogeneity, which was revealed by the findings that LOH at some markers was observed only in the component of ductal carcinoma in situ but not in the invasive component of the same tumors. In addition, some markers were found to preferentially lose at specific tumor grades, implying their contribution to genetic heterogeneity during tumor development. Therefore, this study suggests that breast cancer progression is clonal with regard to CIN, but different breast cancers would present distinct molecular profiles resulting from genetic heterogeneity caused by CIN.
The effects of sodium deoxycholate (Deo-Na), a bile salt, and sodium caprate (Cap-Na), a fatty acid, on the transport of epirubicin were investigated in both the human colon adenocarcinoma (Caco-2) cell line and the everted gut sacs of the rat jejunum and ileum. The possible use of these two potent absorption enhancers as multidrug resistance (MDR) reversing agents also was examined. Epirubicin uptake experiments using a flow cytometer showed that Deo-Na and Cap-Na significantly increased the accumulation of epirubicin in Caco-2 cells. These two enhancers significantly increased apical to basolateral absorption of epirubicin across Caco-2 monolayers and mucosal to serosal absorption of epirubicin in the rat jejunum and ileum. Moreover, the addition of Deo-Na or Cap-Na significantly reduced the basolateral to apical efflux of epirubicin across Caco-2 monolayers. The co-presence of verapamil, one typical P-glycoprotein (P-gp) substrate, and Deo-Na or Cap-Na demonstrated further reduction of epirubicin efflux. The study suggests that inhibition of P-gp or other transporter proteins located in the intestines may be involved, at least partially, in the reduction of epirubicin efflux. In conclusion, the therapeutic efficacy of epirubicin may be improved by the use of such low toxicity excipients as absorption enhancers and MDR modulators in formulations.
OBJECTIVE: To determine the presence and role of proximal conduction block in neuralgic amyotrophy. METHODS: Percutaneous electrical stimulation of cervical roots and brachial plexus was employed in eight patients with neuralgic amyotrophy. Root to Erb's point compound muscle action potential amplitude ratios for abductor digiti minimi, extensor digitorum communis, biceps, and deltoid muscles were compared with results obtained from 10 healthy controls. RESULTS: Conduction block in the nerve to one muscle was found in three of eight patients (38%) suggesting focal proximal demyelination. Repeat studies showed axonal degeneration, resolution, and persistence of conduction block in these three patients respectively. CONCLUSION: Focal conduction block plays a significant part in the pathogenesis of neuralgic amyotrophy, which is generally regarded as an axon loss process. Therapeutic intervention should be directed to patients with persistent conduction block, with the aim of eradicating the block and possibly minimising subsequent axon loss.
BACKGROUND: Quantitative sensory testing has gained popularity as a tool in the diagnosis of peripheral neuropathies. This study aims to establish normative data of quantitative thermal and vibratory thresholds in normal subjects in Taiwan. In addition, we also examined the effect of age and gender differences on these thresholds. METHODS: The study included 100 healthy subjects (50 males and 50 females) who were admitted for regular physical examination. The quantitative testing of thermal, cold and vibratory sensations were performed having recourse to a Thermotest instrument applied on the right hand and foot of these subjects. Measurements included perception thresholds of warm (WT), cold (CT), heat pain, cold pain and vibration as well as a visual analog pain scale. RESULTS: Age was comparable between the sexes, but the male subjects were taller than the female subjects. A higher WT and CT in the hand, but not in the foot, were found in the male subjects in comparison with the female subjects. Heat pain threshold and cold pain threshold of both sites did not significantly differ between genders. Moreover, the groups did not differ in vibration threshold and visual analog pain scale. Young subjects (age < 30 years) showed a higher CT in the foot than the older subjects (age > 50 years). None of the above parameters were different between these two age groups. Overall, the age or height bore no significant relation to the difference between WT and CT (DDWT-CT). CONCLUSIONS: The female subjects were found to be more sensitive to warm and cold stimulation in the hand than their counterparts. These results have provided valuable normative data on sensory perceptive thresholds in Taiwanese, which are useful as a tool in the diagnosis of peripheral neuropathy.
We have examined the role of the breast cancer susceptibility genes BRCA1 and BRCA2 and other loci in the vicinity of these 2 genes on the long arms of chromosomes 17 and 13 (17q and 13q) for the presence of genomic deletions in breast cancer among Taiwanese women. Breast cancer in Taiwan is particularly characterized by its low incidence rate and its early age of tumor onset. Twelve microsatellite markers spanning the region 17q12-21 and 8 microsatellite markers spanning the region 13q12-14 were analyzed for allelic loss or loss of heterozygosity (LOH) in 90 patients with primary infiltrating ductal carcinoma. Compared with the background LOH level (10-12%) estimated by LOH at 4 unrelated loci, 17 markers (11 at 17q and 6 at 13q) demonstrated a significantly increased frequency (21-42%) of allelic loss (p < 0.05). Subsequent construction of deletion maps based on LOH at these significant loci localized the 6 smallest regions of overlap, including those harboring BRCA1, BRCA2, the retinoblastoma gene and 3 novel regions (the 1st located approximately 0.5 to 1 cM telomeric to BRCA1, the 2nd centromeric to BRCA1 flanked by D17S857/D17S846 and the 3rd closely adjacent to BRCA2), suggesting sites of susceptibility genes. Allelic loss at BRCA1 and BRCA2 was specifically associated with poorly differentiated tumors.