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As a result of the "heroic fight" by physicians, many people suffered from painful death in hospitals, inserted with variable tubes and surrounded by different medical devices. In order to improve our quality of death and quality of hospice palliative care, Taiwan passed a Hospice Palliative Care Act (Natural Death Act) in 2000 which gives people the right to choose cardiopulmonary resuscitation or do no resuscitation at the end of life. We are now working forward to the advance care planning to establish a Patient Self Determination Act. In this new Act, people can choose to refuse the terminal painful life sustaining treatments. Hope this will further improve our quality of terminal care. "Birth, aging, sickness and death" are natural course of life. However, with the relentless advancement of medical science and technology, physicians now tend to fight for lives against all the odds. As a result of the "heroic fight" by physicians, many people suffered from painful death in hospitals, inserted with variable tubes and surrounded by different medical devices. Our life span may have increased; however, it appears reasonable to suggest that the quality of life at its end may not have improved (1) .In order to improve the quality of life at end and to ensure good death and peaceful passing, modern hospice care (St. Christopher's Hospice) was started by Dame Cicely Saunders in London in 1967 (2,3). In 1990 the first hospice ward was opened in Taipei's Mackay Memorial Hospital by Dr. David CH Chung in Taiwan (4) .In 2000 Taiwan passed a Natural Death Act (NDA), named Hospice Palliative Care Act (HPCA) to allow patient to have the right of choosing terminal cardiopulmonary resuscitation (CPR) or do no resuscitation (DNR) (3,4). In order to further improve the quality of terminal care, we need to step forward from terminal DNR to advance care planning (ACP) and patient self determination act (PSDA).

Background Glucose intolerance in patients with amyotrophic lateral sclerosis (ALS) has been inconsistently reported. Evidence for the association of ALS and diabetes mellitus is limited. We aimed to assess the overall and age- and sex-specific risks of ALS among patients with diabetes in Taiwan. Methods The study cohort included 615 492 diabetic patients and 614 835 age- and sex-matched subjects as a comparison cohort, followed from 2000 to 2008. We estimated the incidence densities of ALS and calculated the relative hazard ratios (HRs) of ALS (ICD-9-CM 335.20) in relation to diabetes using a Cox proportional hazard regression model, with adjustment for potential confounders, including sex, age, geographic area, urbanization status, Charlson Comorbidity Index, frequency of medical visit, and histories of hypertension, hyperlipidemia, and chronic obstructive pulmonary disease. Results Over a 9-year period, 255 diabetic and 201 non-diabetic subjects developed ALS, corresponding to incidence densities of 7.42 and 5.06 per 100 000 person-years, respectively. After adjustment for potential confounders, patients with diabetes experienced a significantly elevated HR of 1.35 (95% confidence interval [CI], 1.10–1.67). A higher covariate adjusted HR was noted in men (HR 1.48; 95% CI, 1.13–1.94) than in women (HR 1.17; 95% CI, 0.84–1.64), while men aged ≤65 years showed the most increased HR of 1.67 (95% CI, 1.18–2.36). Conclusions This study demonstrated a moderate but significant association of diabetes with ALS onset, and such association is not confounded by socio-demographic characteristics or certain ALS-related co-morbidities. Further studies are warranted to examine whether the findings observed in our study can be replicated.

Background In Taiwan, nearly all medical dispute cases were reviewed by an official Medical Review Committee (MRC). Aims The aim of this study was to investigate the time trends of assessment reports by the MRC to estimate the changing trends of medical malpractice litigation. Methods All assessment reports of the MRC from a nationwide database were reviewed. The assessment reports were analysed according to the year of completion. We further analysed the time trends by adjusting numbers for the size of the general population and numbers of physicians. Stratified analyses were also conducted by region and commission authority. Results Between 1987 and 2006, the MRC completed a total of 5324 assessment reports, with 4949 reports involving a medical dispute and the remaining 375 reports not involving a medical dispute. The numbers of assessment reports increased from 139 in 1987 to 221 in 1996 and 361 in 2006. The assessment increased from 0.70 per 100 000 people in 1987 to 1.03 and 1.58 per 100 000 people in 1996 and 2006 respectively. There was a stable trend of 8.5–10.0 assessments per 1000 physicians annually during the study period. Rising trends were consistent for all regions of Taiwan and for all criminal cases, but increases were more significant for civil cases. Conclusions The numbers of medical dispute cases have increased significantly over the past 20 years. More studies to investigate the reasons of the rising trends and to find resolving methods to decrease the numbers of medical dispute will be helpful in the future.

Background To assess the value of baseline clinical severity and perfusion–diffusion mismatch as predictors for further infarct growth and clinical outcome. Methods Patients with acute ischemic stroke and initial perfusion–diffusion mismatch within 72 h were enrolled. Baseline perfusion defects on time-to-peak (TTP) and cerebral blood volume (CBV) maps were measured. Infarct volume and stroke severity were assessed by diffusion-weighted image (DWI) and NIHSS, and were repeatedly assessed 7 days later. The predictive value of baseline NIHSS and perfusion defects on further infarct growth and neurologic deterioration was determined. Results Fifty-two patients (mean age 68.3 ± 12.8 years, 42% women) were enrolled. CBV defects were significantly associated with infarct growth (CBV, p = 0.02). Initial stroke severity, but not TTP and CBV mismatch ( p = 0.65 and 0.76, respectively), significantly inversely correlated with neurologic deterioration ( p = 0.001). Conclusions In patients with mismatch, those with severe symptoms initially are more likely to have infarct growth, while those with minor symptoms tend to suffer from larger extent of neurologic deterioration within 1 week. CBV is associated with further infarct growth but not clinical deterioration.

Background: Rural living has long been debated as a risk factor for idiopathic Parkinson’s disease (IPD). But few community-based studies compared this difference between urban and rural areas. Methods: Population-based surveys by neurologists using a standardized diagnostic protocol were conducted in the urban areas of Keelung City and compared the prevalence rates of IPD with those we had previously determined in the rural area of Ilan County, Taiwan. Subjects were diagnosed with IPD when at least 2 of the 4 cardinal signs of parkinsonism were present and by exclusion of secondary parkinsonism. Gender-specific age-standardized prevalence rates of IPD by using the 1970 and 2000 US censuses were calculated for comparison. Results: The participation rate was 84.9%. The crude prevalence rate of IPD in persons aged 40 years and over was 706 (95% CI: 551–864) per 100,000 population. The age-adjusted prevalence rates by using the 1970 US census were 633 (95% CI: 620–646) for people aged 40 and over and 230 (95% CI: 227–234) for all ages. Our results were similar to those obtained in Sicily, Rotterdam, and 3 communities in China. Moreover, the prevalence rates of IPD in Keelung, the urban area studied, were twice as high as those in Ilan, the rural area studied (p < 0.001). Conclusions: Our results suggest that urban living is more important as a risk factor for IPD development than rural living in Taiwan.

Background Botulinum toxin type A (BoNT-A) for the treatment of patients with various forms of migraine has been studied, but there is a paucity of data regarding the use of BoNT-A in Asian headache patients. Our study was designed to evaluate the efficacy of BoNT-A in the treatment of transformed migraine (TM) in a population of Taiwanese patients. Methods We retrospectively analyzed 30 patients who underwent BoNT-A treatment for TM from July 2003 to May 2004. Of 30 patients, 14 had palpable muscle tenderness (or tender points) in the pericranial region and 16 did not. All patients received injections into the corrugator, procerus, frontalis, and temporalis muscles (a total of 30 U), while a subset of TM patients with tender points (6 of 14 patients) also received injections to additional muscles based on a follow-the-tenderness approach (mean dose, 45 U). Results Twenty-seven of the 30 patients (90%) surveyed reported effective relief of their symptoms with BoNT-A treatment (at least a 50% reduction in the number of headache days or in headache intensity). The greatest reduction in headache days per month and headache intensity was found in TM patients with tender points who received a mean dose of 45 U compared to those who received fixed-site dosing of 30 U. Conclusion Our results suggest that BoNT-A may be an effective prophylactic treatment for TM in Taiwanese patients. Interestingly, similar efficacy was demonstrated in TM patients with tender points compared to those without tender points when an additional dose of BoNT-A was injected into the tender muscles in the former.

The duty of medical personnel is to save lives, cure diseases, relieve suffering, and promote health. Medical personnel care for their patients from birth to death. At the end of terminal care, medical personnel should maintain a religious / holistic commitment to their patients to "remove their suffering and provide happiness" as much as possible. Mackay Hospital opened the first hospice in Taiwan in 1990. Financial coverage of hospice care by the National Health Insurance, the enactment of the Hospice Palliative Act, the attention of Hospital Accreditation to hospice care, and the establishment of the system of clinical chaplaincy have all contributed to the development of hospice palliative care in Taiwan. Application of the Taiwan Coma Scale has been shown to decrease the use of futile life sustaining treatments in the ICU. The author hopes that nurses may further expand community hospice care services to help facilitate the peaceful dying of terminal patients at home.我國安寧緩和照護之相關政策的過去發展與未來展望.醫護人員要「救生」，也要「顧死」，照顧病人，應該是「從子宮到墳墓」，從出生到死亡，而最後階段的臨終關懷，更應發揮「拔苦予樂」的宗教情操與人文精神。1990年馬偕醫院在淡水分院設立「安寧病房」，是我國安寧療護實務的開始。健保的給付、〈安寧緩和醫療條例〉的立法、醫院評鑑的重視與臨床宗教師制度的建立，使安寧工作能夠順利開展。未來希望加護病房推行台灣昏迷指數，可以縮短臨終病人的痛苦與減少醫療資源的浪費。期許將來能夠全面推廣社區安寧照護，讓大部分的病人能夠壽終正寢，在家中安詳往生。.

To compare the health-related quality of life (HRQL) for patients with epilepsy and health subjects, we collected the clinical and demographic data and information on health states by using the Taiwan version of World Health Organization quality of life (WHOQOL)-BREF questionnaire in 296 patients (aged 19-73 years) with confirmed active epilepsy visiting the clinic of National Taiwan University Hospital, and 296 age-, gender-, municipal- and education-matched Taiwanese healthy subjects sampled from a national health interview survey. Multiple regression analyses with stepwise selection strategy were conducted to study risk factors for impairment of HRQL. Patients with epilepsy have poorer HRQL than the healthy population in physical, psychological and social domains but not in environment domain (p0.005). Patients with less than 4 attacks during the previous 1 month had a better score in the availability and quality of health and social care in environment domain than healthy subjects (p0.05). After controlling other determinants, seizure frequency, and comobid with other diseases are the important factors in predicting HRQL for epilepsy patients. Patients with employment and married had a significantly better HRQL. Effective control of seizure frequency and thoughtful promotion of positive attitudes in community are essential to improve the HRQL of epilepsy patients.

Background: The reported prevalence and incidence rates of PD were significantly lower in China than those in Western countries. People in China and Taiwan have a similar ethnic background. Objective: To investigate the prevalence, incidence, and mortality rate of PD in Taiwan. Method: The authors conducted a population-based survey using a two-stage door-to-door approach for patients aged 40 years or older in Ilan, Taiwan. Patients were diagnosed with PD by having at least two of the four cardinal signs of parkinsonism and exclusion of seconddary parkinsonism. To identify new cases of PD after the survey, patients with negative results of parkinsonism in the first stage were matched to the information on clinical diagnosis of PD from the Bureau of National Health Insurance toward the end of December 31, 1997. All cases of PD were linked to the Taiwan mortality registration to ascertain causes of deaths until December 31, 1999. Results: The participation rate was 88.1% among the 11,411 contacted individuals. Thirty-seven cases of PD were identified. The age-adjusted prevalence rate of PD for all age groups was 130.1 per 100,000 population after being adjusted to the 1970 US census, assuming no cases of PD would be found among those younger than 40 years of age. Of 9972 non-PD subjects in the first screen, 15 new cases of PD were ascertained. The age-adjusted incidence rate was 10.4 per 100,000 population for all age groups. The case fatality rate of PD after a 7-year follow-up was 40.4% (21 deaths in 52 patients with PD). The relative risk of death for PD cases versus non-PD cases was 3.38 (95% CI: 2.05–4.34). The 5-year cumulative survival rate in PD cases (78.85%) was statistically lower than that in non-PD cases (92.84%). Conclusion: The prevalence and incidence rates of PD in Taiwan were much higher than those reported in China, but closer to those in Western countries. These results suggest that environmental factors may be more important than racial factors in the pathogenesis of PD.

Pathological diagnosis of neuropathy has traditionally depended on ultrastructural examinations of nerve biopsy specimens, particularly for sensory neuropathies affecting unmyelinated and small-myelinated nociceptive nerves. These sensory nerves terminate in the epidermis of the skin, and the pathology of neuropathy usually begins from nerve terminals. We investigated the feasibility of diagnosing small-fiber sensory neuropathy by evaluating cutaneous innervation. Skin biopsy specimens of 3-mm in diameter were obtained from the distal leg and the distal forearm of 55 healthy controls and 35 patients with sensory neuropathy. In the healthy controls, conventional intraepidermal nerve fiber densities (IENF densities) as measured using the image analysis system in the distal forearm and in the distal leg were correlated (r=0.55, P0.0001), with significantly higher values in the distal forearm than in the distal leg (17.07+/-6.51 vs 12.92+/-5.33 fibers/mm, P0.001). Compared to IENF densities of healthy controls, these values of neuropathic patients were significantly reduced in the distal forearm (5.82+/-6.50 fibers/mm, P0.01) and in the distal leg (2.40+/-2.30, P0.001). We further explored the possibility of quantifying skin innervation by counting "ocular intraepidermal nerve fiber density" (ocular nerve fiber density) with no aid of an image analysis system. This was based on the fact that the epidermal length on specifically defined sections was very close to the predicted epidermal length of 3 mm, the diameter of skin punches (P=0.14). Ocular nerve fiber densities were significantly correlated with IENF densities as measured by the image analysis system (r=0.99, P0.0001). Dermal nerve fibers of neuropathic patients either disappeared or became degenerated. These findings were consistent with the notion of early terminal degeneration in neuropathy, and will facilitate quantitative interpretation of epidermal innervation in human neuropathy.

To analyse the effect of epilepsy an P300 event-related potentials we studied 27 patients with idiopathic generalized epilepsy (IGE), 13 patients with temporal lobe epilepsy (TLE) and 60 normal controls. The prolongation of P300 latencies was highly cor related with increasing age in controls but not epileptic patients. The age-corrected P300 latency used in this study was actual P300 latency–predicted P300 latency (predicted P300 (msec)=306.20+0.79 age, P =0.001, R 2 =0.32). By using ANOVA analysis, the age-corrected latencies of P300 were significantly longer in TLE patients (19.72±47.82 msec, mean±SD) than in IGE patients (10.97±36.97 msec) and controls (0.23±20.28 msec). Likewise, significantly prolonged P300 latencies were seen in the epileptic patients with a seizure frequency more than 400 times (37.21±47.50 msec). The multivariate-adjusted odds ratio for those who had TLE was 10.97 (95% CI=3.99 − 30.14 ) in the prolonged latencies of P300 compared with that of IGE patients. The odds ratio of longer latencies of P300 was 7.43 (95% CI=2.75 − 20.08) among those who had a high seizure frequency (≧400 times) compared with those who had a low seizure frequency. No interaction between TLE and high frequency of attacks was found. The age at onset of seizure and duration of illness was not associated with P300 latency prolongation. From the above results, we might infer that the seizure type of TLE and a high frequency of seizure are two major independent precipitate factors for abnormal latencies of P300 in the epileptic patients.

(-)-Deprenyl (DEP) had been shown to slow of progression of Parkinson's disease (PD). The present study sought to determine whether DEP would attenuate the nigrostriatal system damage induced by intranigral administration of the herbicide paraquat (PQ) as a model of parkinsonism in vivo. Neurochemical and behavioral observations of Wistar rats were the focus of our study. In the neurochemical observation, the PQ injected in the rats caused dose-dependent depletion of dopamine (DA) in the ipsilateral striata. The coadministration of DEP with PQ partially increased the striatal DA level. The prediction of the striatal DA levels was calculated by regression coefficients obtained from multiple linear regression (r(2) = 0.82): DA level (% of control) = 103.34 - 9.58 PQ (nmol) + 0.79 DEP (nmol). It was demonstrated that the high dose of 20 nmol DEP could significant attenuate the PQ (5 nmol)-elicited dopaminergic toxicity (p < 0.05). In the behavioral observation, the intranigral injection of PQ into the rats caused a rotation behavior contralateral to the lesioned side in response to apomorphine administration (0.5 mg/kg, sc). This apomorphine-induced rotational behavior could also be attenuated significantly by coadministration of DEP (20 nmol) and PQ (5 nmol) compared with PQ-treated (5 nmol) animals (p < 0.05). The above observations indicate that DEP could provide a protective effect on the moderate injury elicited by PQ toxicity of the nigrostriatal dopaminergic system. DEP might be a useful therapeutic agent in treating patients with early-stage PD.

The synthesis and the phase behavior of stilbazoles and corresponding N-oxides containing different positions of heterocyclic N atoms, i.e. trans-2'-, 3'-, 4'- stilbazoles and their N-oxides, are reported. Their phase transition temperatures and the mesogenic behavior were investigated through the DSC, polarizing optical microscope and X-ray diffraction (XRD) measurements. Increasing dipole moments by oxidation of stilbazoles to analogous N-oxides induces the S A phase with an interdigitated bilayer packing. Both 2'-stilbazoles and analogous N-oxides do not possess mesogenic phases, which may he due that π electron polarizabilities are reduced by the molecular twist originated from dipoles along the ortho-direction. Besides, the positonal effects of the N-oxides on mesogenic properties are more distinct than those of analogous stilbazoles, and new mesogenic phases have been generated by tuning the position of the N-oxide function in the charged liquid crystals. Consequently. unique mesogenic properties may he introduced through adjusting the dipolar direction and strength of the heterocyclic atoms in the molecules.

The influence of body temperature on focal cerebral ischaemia-reperfusion was investigated by using a well established rat stroke model. Three different degrees of ischaemia were created in the cerebral cortex of the right middle cerebral artery territory by varying the duration of clamping of the bilateral common carotid arteries and the right middle cerebral artery with full reperfusion. Mild hyperthermic (body temperature 38-39 degrees C) influence during ischaemia significantly enhanced the severity of infarction in mild (30 min) ischaemia, mean infarct volume was 78% greater than normothermic (body temperature 36.5-37.5 degrees C) group (P < 0.001); and in moderate (60 min) ischaemia, mean infarct volume was 23% greater than in the normothermic group (P < 0.05); but no difference between the two groups was observed in severe (90 min) ischaemia. Our data suggest that mild whole body hyperthermia during focal ischaemia-reperfusion has a detrimental effect on the infarct volume only in mild and moderate ischaemia in this model.

Carbamazepine and phenytoin, two of the most commonly prescribed antiepileptic drugs, have been proposed to share a similar mechanism of action by use-dependent inhibition of Na+ channels. The proposed similar mechanism of action, however, cannot explain the common clinical experiences that the two drugs are different; in some patients, one drug may be more effective than the other. This may occur even when optimal therapeutic concentrations are reached with both medications in plasma or the cerebrospinal fluid. In this study, we show that the action of the two drugs on Na+ channels are quantitatively very different. The affinity between inactivated Na+ channels and carbamazepine (apparent dissociation constant approximately 25 microM) is approximately 3 times lower than that of phenytoin, yet the binding rate constant of carbamazepine onto the inactivated Na+ channels is approximately 38,000 M(-1)/sec(-1), or approximately 5 times faster than that of phenytoin. It is speculated that carbamazepine may be more effective than phenytoin in treating seizures whose ictal depolarization shift is relatively short, whereas a better response to phenytoin may imply abnormal discharges characterized by more prolonged depolarization.

Background: Thiazolidinediones (TZDs) - rosiglitazone and pioglitazone - a class of insulin sensitizer for treating type 2 diabetes, have been reported to exhibit neuroprotective effects in preclinical studies and have good effects in the control of blood sugar for diabetic patients with insulin resistance. However, clinical trials and observational studies have raised the possibility of higher stroke risk in patients treated with rosiglitazone. Whether pioglitazone poses similar stroke risk remains uncertain. Most of the studies on cardiovascular effects of TZDs were based on studies in the USA and Europe. The present study aimed to compare the stroke risk among diabetic patients on TZD to those on non-TZD medications in an Asian population. Methods: The study cohort included 15,981 patients with a diagnosis of diabetes without prior stroke, acute myocardial infarction (AMI) or heart failure who were followed from 2001 to 2010. Patients were classified by their prescriptions into rosiglitazone, pioglitazone and non-TZD groups. The study end points included ischemic and hemorrhagic stroke. In view of the reported association of heart failure and AMI with rosiglitazone, these 2 end points were also included in the present study. Cox hazard proportional models were used to estimate the risk of developing the end points. Likelihood ratio test was used to examine the age-drug interactions. Dose-response effects were evaluated by comparing the incidence rates among patients with different cumulative exposures to TZD. Results: During the 10-year follow-up, the rosiglitazone group showed significantly higher risk of ischemic stroke (multivariate adjusted hazard ratio, HR = 1.39; 95% confidence interval, CI = 1.16-1.66) and heart failure (HR = 1.59; 95% CI = 1.18-2.14) than the non-TZD group. The pioglitazone group did not show significant difference from the non-TZD group in ischemic stroke (HR = 0.97; 95% CI = 0.75-1.26) and heart failure (HR = 0.94; 95% CI = 0.59-1.50). The results also showed a significant dose-dependent effect of higher risk of ischemic stroke with increasing dosage of rosiglitazone, while there was no increased risk at any level of pioglitazone dosage. Conclusions: This population-based cohort study shows that rosiglitazone imposes a higher risk of developing stroke or heart failure in this Asian patient population, suggesting the adverse side effects of rosiglitazone across ethnic boundaries. Pioglitazone, on the other hand, does not increase cardiovascular or stroke risk compared to the non-TZD group among diabetic patients without a history of macrovascular disease.

To examine the association between anticardiolipin (aCL) antibodies and epilepsy, we inves tigated the serum titers of aCL antibodies in a total 252 systemic lupus erythematosus (SLE) patients recruited in a prospective study. Twenty-one cases with epilepsy which were not attributable to any causes other than SLE were identified after being followed-up for five years. The clinical manifestations were recorded and blood samples were tested for the presence of aCL antibodies (IgG, IgM and IgA isotypes). Among 21 patients with epilepsy, 12 (57.1%), 2 (9.5%) and 2 (9.5%), respectively, had elevated baseline serum levels of IgG, IgM and IgA aCL antibodies. There was a dose-response relationship between risk of seizure and the baseline serum level of aCL antibodies ( P < 0.01). The odds ratio of developing seizure were 3.7 for those who had a high level of aCL antibodies compared with those without a detectable level of aCL antibodies as the referent. Our results indicate that epilepsy as a primary neuropsychiatric event among lupus patients is associated with a high titer of aCL antibodies.

A double-blind, placebo-controlled, parallel-group, multicentre study was conducted to evaluate the efficacy of pentoxifylline (Trental) in patients with multi-infarct dementia (MID) according to DSM-III-R criteria. Men and women aged 45 years or older, with a Hachinski Ischemia Scale scoreor = 7 and a Mini Mental State Examination (MMSE) score of 10-25 at entry, and computed tomographic evidence of vascular disease were enrolled. A total of 289 patients were randomised to receive either oral pentoxifylline 400 mg t.i.d. or placebo for 9 months, and efficacy was assessed every 3 months. The primary outcome variable was the difference in scores between the two treatment groups, as measured on the Gottfries, Bråne, Steen (GBS) scale. Secondary outcome variables included the scores achieved on the Sandoz Clinical Assessment Geriatric (SCAG) scale and MMSE, and a battery of psychological and other tests. The intention-to-treat analysis for patients completing the study (n = 239) showed a statistically significant difference in the total GBS score in favour of pentoxifylline (improvement of 3.5 points, p = 0.028). A significant difference in the total GBS score in favour of pentoxifylline was even almost achieved in the intention-to-treat analysis for all evaluable patients (n = 269, improvement of 2.1 points, p = 0.065). It is concluded that treatment with pentoxifylline is beneficial for patients with MID, the global results of the GBS and SCAG scales being reinforced by significant improvements in those subscales specific for intellectual and cognitive function.

A scheme, based on the four‐layer inhomogeneous spherical model of the head with an electric dipole in it, is proposed for localizing the epileptic focus. From the result of stability test, we find that the gradient project method used for computing an inverse solution of the model has a fast convergence speed. The convergence has very good stability which is not affected by different initial values. Spikes for three patients with different disorders are used for localizing the epileptic discharge sources. For the two patients with lateralized spikes, results from the dipole locations are very similar to the inspections by clinical physicians. However, for the other one with generalized spikes, we fail to localize the discharge source with acceptable accuracy. Thus, we conclude that the electric dipole model with the lateralized spikes is valuable in localizing epileptic discharge sources.

The dose-dependent effects of the anticholinesterases, neostigmine and mycotoxin territrem-B, were determined on: (i) Cl − -responses of voltage clamped Achatina fulica neurons to microperfused acetylcholine; (ii) the 4 K + -induced outward currents evoked by an electrogenic sodium pump in the same neuron; and (iii) acetylcholinesterase activity of Achatina fulica ganglionic homogenates. Both compounds at low doses potentiated the peak acetylcholine responses. However, they had different effects at higher (> l μM) doses in that neostigmine now antagonized acetylcholine responses, while territrem-B still produced a maximal potentiation. At all doses neostigmine produced a dose-dependent inhibition of acetylcholinesterase activity. The cholinolytic effect of high doses of neostigmine was associated with the inhibition of 4K + -induced current in the same neuron, while territrem-B neither altered the K + -induced current nor antagonized acetylcholine responses. The cholinolytic effect of neostigmine was completely antagonized by the inhibition of electrogenic sodium pump by ouabain or by perfusion with K + -free solution. These results suggest that neostigmine at high concentrations inhibits the electrogenic sodium pump and that the cholinolytic effect of high doses of neostigmine is secondary to this action. Territrem-B, on the other hand, had no effect on the electrogenic sodium pump and had no effect on the neuronal membrane properties other than to inhibit acetylcholinesterase. Thus, territrem-B may be a useful tool for studying the interaction between acetylcholinesterase and acetylcholine receptors.

The hemodynamic classification of the CCF has important implications for prognosis and therapy, but satisfactory criteria for such a differentiation are still lacking. We studied the application of extracranial duplex sonography in 14 cases of CCF with emphasis on the hemodynamic parameters of the RI and flow volume and made a correlation with the angiographic findings. We conclude with proposed duplex sonographic criteria for hemodynamic classification: (1) small RI with increased flow volume in the ICA: direct ICA-cavernous sinus fistulas (type A); (2) normal RI and flow volume in the ICA and ECA: dural branch of ICA-cavernous sinus fistulas (type B); (3) small RI with or without increased flow volume in the ECA: dural branch of ECA-cavernous sinus fistulas (type C) or dural branches of ICA- and ECA-cavernous sinus fistulas (type D). Application for assessment of the therapeutic effectiveness was also demonstrated.

We studied the risk factors that influence the occurrence of response fluctuations and dyskinesias in 194 patients with Parkinson's disease (PD). These factors included age at onset, disease severity at levodopa initiation, duration of illness prior to levodopa therapy and the daily dose of levodopa at the end of study. The first three were fixed covariates and the last one was time-dependent. Patients with age onset before 50 years showed a higher risk of developing response fluctuations (RF) and dyskinesias in univariate analysis. We estimated the combined effects of these covariates through multivariate analysis and found that the age at onset was the sole factor related to the incidence of both complications. Additionally, it was the only variable that could enter the predictive model of stepwise regression. Our observation suggested that age at onset determined the occurrence of RF and dyskinesias. Patients with younger age at onset had higher risk of developing these adverse effects.

The effectiveness of acupuncture in acute stroke remains largely untested and unproved. A randomized, controlled trial was carried out to study the feasibility of acupuncture in combination with conventional supportive treatment for acute stroke patients. A total of 30 patients, aged 46-74, with the onset of symptoms within 36 h were enrolled into the study after appropriate screening. All patients gave informed consent. Basing on the same supportive treatment, patients were randomly assigned to a treatment with or without acupuncture. The procedure and acupoint selection were discussed and decided through several meetings of a group of senior acupuncture doctors in Taiwan. Acupuncture was applied 3 times/week for 4 weeks. During the study period, there were no problems in conducting this trial in terms of patient availability and acceptance, and physician cooperation. A significantly better neurologic outcome was observed in the acupuncture group on day 28 and day 90. The improvement in neurologic status was greatest in patients with a poor neurologic score at baseline. There were no important side effects except for one episode of dizziness related to acupuncture treatment. The data and results of this study will be used as a guideline for planning a full-scale clinical trial, e.g. sample size calculation, method of randomization with stratification of prognostic factors, choosing acupuncture points and technique of acupuncture.

We reviewed the cerebrovascular complications of 158 episodes of infective endocarditis occurring in 155 patients. Cerebrovascular complications occurred in 21 patients (14%). The incidences of cerebral embolism, intracerebral hemorrhage, and subarachnoid hemorrhage were 10%, 3%, and 1%, respectively. Death occurred in 33% of patients with cerebrovascular complications and 4% without. Patients whose condition was complicated by intracerebral hemorrhage had an even greater rate of mortality (80%). Sixty-two percent of cerebrovascular complications occurred within 2 days of antibiotic therapy; 29% occurred 2 weeks later. Two of three patients receiving open-heart surgery within 2 days of cerebrovascular complications died. Seventeen of 133 patients with native valve endocarditis and 4 of 22 patients with prosthetic valve endocarditis had cerebrovascular complications. Echocardiographic evidence of vegetation was seen in 120 patients, and cerebrovascular complications were noted in 16 patients. Twelve of 62 patients with mitral valve involvement detected by echocardiography and 4 of 40 patients with aortic valve involvement had cerebrovascular complications. According to the findings of surgery or pathology, 4 of 24 patients with mitral valve involvement and 4 of 36 patients with aortic valve involvement had cerebrovascular complications. We conclude that vegetation detected by echocardiography does not increase the risk of cerebrovascular complicatons; there is no difference in the incidence of cerebrovascular complications between the mitral and aortic valve groups, either by the involvement of vegetation detected by echocardiography or the surgical or pathologic findings; there is no difference in the incidence of cerebrovascular complications when comparing the native and prosthetic valve groups or the streptococcus viridans and Staphylococcus aureus groups; cerebrovascular complications, especially intracerebral hemorrhage, increase the risk of mortality in patients with infective endocarditis; although most cerebrovascular complications occurred within 2 days of antibiotic therapy, late onset of cerebrovascular complications are not uncommon; and it is better to avoid early open heart surgery in patients whose condition is complicated by intracerebral hemorrhage or hemorrhagic infarction.

Madelung's disease (multiple symmetric lipomatosis) is a rare disease characterized by abnormal diffuse lipomatosis in proximal upper limbs and neck. Previous reports have shown that this disease is associated with alcoholism, polyneuropathy, mitochondrial disease, and glucose intolerance. Here, we describe a 46-year-old man having Madelung's disease associated with polyneuropathy and symptomatic hypokalemia. He presented with insidious-onset weakness and numbness in lower limbs for 7 years and recent deterioration of symptoms. Proximal weakness improved with potassium supplement. Our observation may extend the phenotype of Madelung's disease to hypokalemic periodic paralysis.

Objectives The natural course of Parkinson’s disease (PD), as measured on the Hoehn-Yahr (H-Y) scale, and the impact that early detection would have on prognosis for those with the disease, has barely been addressed since the introduction of L-dopa. This study aimed to elucidate the natural history of PD and effectiveness of early detection in reducing advanced disability and mortality. Method A total of 21 362 participants aged 40 years or older were invited to two community-based programmes for the early detection of PD. The step-by-step annual progression rates from H-Y stage I to stage IV or V, and cumulative survival rates, by the H-Y scale, were estimated and applied to simulated data to assess the impact of different screening intervals upon stage at diagnosis and subsequent survival. Results The average duration in stages I, II and III was estimated as 2.83, 6.62 and 1.41 years, respectively. The average delay time before deteriorating into H-Y stage III was 9.45 year. Application of these parameters to simulated model predicted a 36% (95% CI: 28–39%), 26% (95% CI: 20–32%) and 19% (95% CI: 13–24%) reduction in death for annual, 5-yearly and 10-yearly screening programmes, respectively. Conclusion The present study recommended a 5-yearly screening programme, with 74% of PD cases prevented from progressing to H-Y stage III or worse within 10 years of diagnosis, and leading to a corresponding 26% reduction in mortality.

Elevated serum homocysteine levels have been associated with the development of Alzheimer's dementia (AD). The combined use of a mecobalamin capsule preparation, which contains vitamin B12 0.5 mg with an active methyl base, and an over-the-counter nutritional supplement that contains folic acid 1 mg and pyridoxine hyperchloride 5 mg may be effective as a homocysteine-lowering vitamin regimen.The aim of this study was to determine whether oral multivitamin supplementation containing vitamins B6 and B12 and folic acid would improve cognitive function and reduce serum homocysteine levels in patients with mild to moderate AD.This randomized, double-blind, placebocontrolled trial was conducted at En Chu Kong Hospital, Taipei, Taiwan. Male and female patients aged50 years with mild to moderate AD and normal folic acid and vitamin B12 concentrations were enrolled. All patients received treatment with an acetylcholinesterase inhibitor and were randomized to receive add-on mecobalamin (B12) 500 mg + multivitamin supplement, or placebos, PO QD for 26 weeks. The multivitamin contained pyridoxine (B6) 5 mg, folic acid 1 mg, and other vitamins and iron. Serum homocysteine level was measured and cognitive tests were conducted at baseline and after 26 weeks. The primary efficacy outcome was change in cognition, measured as the change in score from baseline to week 26 on the Alzheimer's Disease Assessment Scale 11-item Cognition subscale. Secondary efficacy outcomes included changes in function in performance of activities of daily living (ADLs) and concentrations of homocysteine, B12, and folic acid. Tolerability was assessed by comparing the 2 study groups with respect to physical examination findings, including changes in vital signs, laboratory test abnormalities, concomitant medication use, and compliance of study medication was assessed using an interview with the patient's caregiver, as well as the monitoring of adverse events (AEs) throughout the study.Eighty-nine patients (45 men, 44 women; all Taiwanese; mean [SD] age, 75 [7.3] years) were enrolled and randomized. Overall, there were no significant differences in cognition or ADL function scores between the 2 groups. At week 26, the mean (SD) between-group difference in serum homocysteine concentration versus placebo was -2.25 (2.85) micromol/L (P = 0.008), and the mean serum concentrations of vitamin B12 and folic acid were significantly higher (but within normal range) in the multivitamin group compared with placebo (., +536.9 [694.4] pg/mL [P0.001] and +13.84 ng/mL [11.17] [P = 0.012] at 26 weeks, respectively). The 2 most common AEs were muscle pain (11.1% and 6.8%) and insomnia (8.9% and 9.1%) in the multivitamin and placebo groups, respectively.In this population of patients with mild to moderate AD in Taiwan, a multivitamin supplement containing vitamins B(6) and B(12) and folic acid for 26 weeks decreased homocysteine concentrations. No statistically significant beneficial effects on cognition or ADL function were found between multivitamin and placebo at 26 weeks.

Background/Aims: It is estimated that there are 90,000 patients with dementia in the 23 million habitants of Taiwan, with a few institutions specialized in dementia care. To assess the need of institutional care for dementia, we investigated the institution prevalence of dementia. Methods: We performed stratified randomized sampling of elder residents from different types of institutions in different regions of Taiwan. A 2-stage survey with screening and clinical confirmation was carried out in 2004. Results: In total, 1,525 residents aged 65 years and over in 60 institutions participated in the study in which 1,308 elders completed the 2-stage survey. Among these, 631 elders were diagnosed as having dementia. The dementia prevalence was 26.8% in the residential houses, 61.8% in the assisted living facilities and 64.5% in the nursing homes. Vascular dementia was the leading cause of dementia in the institutions. Old age, diabetes mellitus and family history of dementia increased risks for both Alzheimer’s disease and vascular dementia. Conclusion: The investigation showed that the prevalence of dementia in the long-term care units of Taiwan was much higher than those from community studies and the high prevalence in the institutions depended on the type of the long-term care unit.

Purpose To determine the prevalence rate and patterns of adult patients with epilepsy in Taiwan, we conducted a community-based neuroepidemiological survey. Methods Epilepsy was detected by neurologists using one-stage method. It was integrated into a community health screening service and performed from 1 January 2001 to 31 December 2001 in Keelung, a northern city in Taiwan. A total of 13,663 subjects aged 30 years or older participated in this survey. Results There were 52 patients with epilepsy in this study. Among them, 37 were patients with active epilepsy. The age-adjusted prevalence rate of active epilepsy above 30 years old was 2.77/1000 (to the 1980 US population) with the highest rate in subjects aged 40–49 years (4.0/1000). There was a trend of higher prevalence rate in male than in female. The most common seizure type was complex partial seizure (46.0%). Using one-stage detection method, we found nine (24.3%) patients with active epilepsy who had never been diagnosed before. Among the patients with active epilepsy, 35.1% were symptomatic cases. Head injury (13.5%) is the leading cause, followed by CNS infection (8.1%), stroke (5.4%) and perinatal insult (5.4%). The lifetime prevalence rate of epilepsy (including active epilepsy and epilepsy in remission) was 3.14/1000 for age above 30 years. Conclusions Comparing to previous epilepsy survey in 1993, our results showed that the prevalence rate of epilepsy was rather stable over the past decade in northern Taiwan. Head injury is the leading cause responsible for active epilepsy. Improving public safety is an important public health issue which may help to reduce occurrence of epilepsy.

To investigate mortality in adult patients with epilepsy in Taiwan, a total of 263 patients with epilepsy agedor = 17 years, referred to the outpatient epilepsy clinic between 1 Jan and 31 December 1991, were prospectively enrolled and followed up until 31 December 2000. A total of 32 deaths were reported. Overall case-fatality rate was 12.2%. The age-adjusted standard mortality ratio (SMR) was calculated to compare the risk of death in patients with epilepsy to the general population. Patients with epilepsy had a 3.5-fold higher risk of death as compared with the general population (SMR: 3.47, 95% CI: 2.46-4.91). The Cox proportional hazards regression model was used to assess relevant clinical contributions to death. Patients with an age-at-onsetor = 40 years had a 4-fold higher risk of death as compared with those with an earlier onset. The multivariate analysis revealed that age-at-onset between 40 and 59 years, tumor etiology, and being male increased the risk of death in epilepsy. One-third of the deaths in patients with age-at-onset between 40-59 years died of liver cirrhosis and hepatoma. Hepatitis B virus infection is endemic in Taiwan, and this is closely associated with liver cirrhosis and hepatoma. Whether anticonvulsants contributed to the hepatotoxicity that led to fatal liver disease in this group needs further investigation.

The aim of this study was to investigate the association of intima media thickness (IMT) and plaque with risk factors for atherosclerosis in asymptomatic subjects in Taiwan. Between 1998 and 2001, the study recruited 1781 asymptomatic subjects (1131 men and 650 women [mean age, 49 years; range 18-85 years]). These were examined by B-mode ultrasound to measure the IMT at the far wall of the common carotid artery (CCA) and the extent of plaque formation. A wide range of vascular risk factors including age, gender, smoking, body mass index, blood chemistry, and previous history were surveyed. The mean (+/-S.D.) IMT observed was 0.68 (+/-0.12) and 0.66 (+/-0.11) mm for men and women, respectively, (P=0.0008). The mean (S.D.) IMT of the CCA was 0.66 (+/-0.12) mm on the right side and 0.68 (+/-0.12) mm on the left side (P=0.0004). IMT increased with aging, according to the equation IMT=(0.005xage in years)+0.403 [corrected]. Higher IMT was associated with male gender, and IMT was greater in the left CCA. About 36.9% of subjects had carotid plaques. The percentage of plaque increased with aging. The plaque prevalence was positively associated with IMT. The value of IMT over the cut point of 0.68 mm correlated with obviously increased risk of carotid atherosclerosis. Age, systolic blood pressure and fasting blood sugar were independent risk factors related to both carotid atherosclerosis and thick IMT.

l-Deprenyl (Selegiline), a selective and irreversible type B monoamine oxidase inhibitor, has been used as an adjunct to levodopa therapy in Parkinson's disease. Recently, it is proposed as a putative neuroprotective agent in delaying the progression of cell death based on its capability of reducing the oxidative stress derived from the MAO-B dependent metabolism of dopamine, and blocking the development of MPTP-parkinsonism. However, a variety of experimental models suggest that l-deprenyl provides neuroprotection through multiple modes of mechanism other than the inhibition of MAO-B. We have previously shown that l-deprenyl protects midbrain dopamine neurons from MPP+ toxicity by a novel antioxidant effect. In the present study we examined whether the protection against MPP+ toxicity is also shared by other reversible or irreversible MAO-B inhibitors including (+)-deprenyl, Ro16-6491 and pargyline. Our data show that non of these MAO-B inhibitors changes the dopamine loss in the striatum induced by intranigral injection of MPP+. Our result suggests that l-deprenyl may possess a unique neuroprotective action on nigral neuron against MPP+ toxicity independent of the MAO-B inhibition.

The purpose of this report is to discuss the value of ultrasonographic examination in the diagnosis and follow-up evaluation of vertebral artery dissection. We collected data on 8 patients with 11 pathologic vessels: 9 were affected intracranially and 6 were affected extracranially. Four vessels were affected in both intracranial and extracranial segments. Extracranial color-flow duplex sonography could detect abnormalities in every extracranial vertebral artery dissection. Most abnormal findings were non-specific, including severely reduced flow, absence of flow, and absence of diastolic flow. A specific finding (intramural hematoma) was noted in one artery. Abnormal transcranial color-coded sonographic findings included absence of flow, reduced velocity and reversed flow direction. Three intracranial dissecting arteries showed normal findings on transcranial color-coded sonography. Ultrasonographic follow-up study revealed evidence of improvement; this was noted almost exclusively in the extracranial segments of the vertebral artery but infrequently in the intracranial segment. Extracranial color-flow duplex sonography is sensitive in the detection of extracranial vertebral artery dissection, both in initial diagnosis and in follow-up evaluation.

Background and Purpose To better understand the clinical pattern and further elucidate the risk factors and outcome in different subtypes of cerebral infarction (CI) of the Chinese in Taiwan, we analyzed the National Taiwan University Hospital Stroke Registry in 1995 and performed an ethnic comparison with similar data banks. Methods From the National Taiwan University Hospital Stroke Registry in 1995, 676 patients (383 men and 293 women; mean age, 64.9 years; SD, 13.8 years; range, 1 to 98 years) with CI were recruited for this analysis. CI was classified into five subtypes based on clinical manifestations, ultrasonographic studies, and neuroimaging findings: large-artery atherosclerosis, lacunae, cardioembolism, other less common determined causes, and undetermined cause. Vascular risk factors, extracranial carotid artery atherosclerosis, and 30-day case-fatality rates were investigated in each subtype of CI. Results Of all CI patients, 17%, 29%, 20%, 6%, and 29% were classified as large-artery atherosclerosis, lacunae, cardioembolism, other determined causes, and undetermined cause subtypes, respectively. The present results were compared with those from eight similar Western stroke registries. The relative incidence of lacunar CI in Chinese patients was more common, but large-artery atherosclerotic CI was less common than in whites. Hypertension was frequently seen in CI patients, especially in those with lacunae (85%) and large-artery atherosclerosis (69%). Patients with cardioembolism had a higher percentage of atrial fibrillation (69%), left ventricular hypertrophy, and ischemic heart disease than the other patients. Patients with large-artery atherosclerosis had more vascular risk factors, such as hypertension, diabetes mellitus, smoking, and carotid stenosis. Cardioembolic patients had higher case-fatality rates than other CI patients. Of the cardioembolic patients, 17.3% and 21.8% died within 30 days and during hospitalization, respectively. Conclusions The proportion of CI subtypes varied in different stroke registries. This may be partly due to applied classification criteria and racial-ethnic differences. Awareness of the risk factors and outcome in each subtype of stroke may afford further insights into the surveillance and treatment of cerebrovascular disease.

To explore environmental risk factors for Parkinson's disease (PD) in Taiwan, we investigated 120 patients with PD and 240 hospital control subjects matched with patients on age (± 2 years) and sex. Based on a structured open-ended questionnaire, we carried out standardized interviews to obtain history of exposure to environmental factors, including place of residence, source of drinking water, and environmental and occupational exposures to various agricultural chemicals. In the univariate analysis, the history of living in a rural environment, farming, use of herbicides/pesticides, and use of paraquat were associated with an increased PD risk in a dose-response relationship. After adjustment for multiple risk factors through conditional logistic regression, the biological gradient between PD and previous uses of herbicidesipesticides and paraquat remained significant. The PD risk was greater among subjects who had used paraquat and other herbicide/pesticides than those who had used herbicides/pesticides other than paraquat. There were no significant differences in occupational exposures to chemicals, heavy metals, and minerals between PD patients and matched control subjects. The duration of drinking well water and alcohol consumption was not significantly associated with PD. There was an inverse relationship between cigarette smoking and PD. Environmental factors, especially exposures to paraquat and herbicides/pesticides, may play important roles in the development of PD in Taiwan.

Effects of paraquat on the substantia nigra of the male Wistar rats we re studied pharmacologically by a intracerebral injection of paraquat. The neurochemical, morphological, and behavioral changes observed after a unilateral intranigral injection of paraquat (1-5 microgram) were as follows: (1) neurochemically, paraquat caused dose-dependent depletion of dopamine in the ipsilateral striatum starting 2 weeks after treatment; this effect was long-lasting and irreversible. The ipsilateral striatal dopamine level in animals treated with 3 microgram paraquat was even decreased by 91.5%. (2) Morphologically, 2 microgram of paraquat produced marked loss of Nissl substances and prominent glial reaction in the substantia nigra, while 3 microgram of paraquat caused a severe loss of neurons. (3) Behaviorally, paraquat caused a vigorous rotational behavior in rats contralateral to the lesioned side in response to apomorphine administration (0.5 mg/kg, sc). This effect was dose-dependent and lasted for the entire 16-week experimental period. Taken together, these data indicate that intranigrally injected paraquat may possess marked neurotoxicity and induce degeneration of the rat nigrostriatal dopaminergic system.