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Biomedical subjects

P Kwan

Publications and source records attributed to P Kwan.

At least 19 recordsLinked to original sources
PubMed2006

Finding the missing link between ictal bradyarrhythmia, ictal asystole, and sudden unexpected death in epilepsy.

Basic science studies of the human brain have supported the cortical representation of cardiovascular responses, including heart rate variability. Clinical observations of ictal bradyarrhythmia may be mechanistically explained by the influence of the central autonomic network, although the localization and lateralization issues need to be considered in the light of patterns of seizure spread, hand dominance, and presence of lesions. Ictal bradyarrhythmia also offers a mechanistic explanation of sudden unexpected death in epilepsy (SUDEP), though it may explain only some but not all cases of SUDEP. The missing links are (1) clinical evidence of common factors shared by patients with ictal bradyarrhythmia and patients who die from SUDEP, (2) evidence of arrhythmia as a risk factor for SUDEP from epidemiological studies, and, (3) determination of the importance of ictal bradyarrhythmia in SUDEP with respect to other proposed mechanisms including apnea and intrinsic cardiac abnormalities. There remains a need to review the seizure mechanisms in cases of SUDEP and to step up the amount of concurrent ECG/intracranial EEG analysis in both ictal bradyarrhythmia and SUDEP cases.

Autonomic Nervous System↗
PubMed2005

Gender differences in suicide risk by socio-demographic factors in Hong Kong.

Some peculiarly low male-to-female suicide ratios have been reported in the Far Eastern populations. This article attempts to investigate whether there are gender differences in suicide risk by socio-demographic factors in Hong Kong, and hereby to explain the low male-to-female suicide ratios. The effects of marital status, duration-of-residence, and occupational status on suicide are first studied by periodic suicide rates in 1990-1992, and 2000-2002, then by Poisson regression. Some interesting results are found: Unlike most findings elsewhere, migration in Hong Kong did not induce suicide; occupational status was negatively related to suicide only for men but not for women; the particularly low male-to-female suicide ratio was not due to a larger protection from marriage for men than for women as reported in the literature, but very probably to a very high suicide rate for the non-working population. The authors suggest some plausible explanations of the findings and hence further research to be conducted.

Adult↗
PubMed2004

The natural history of epilepsy: an epidemiological view.

Better information of the natural history of epilepsy has important implications for understanding the underlying neurobiology, evaluating treatment strategies, and planning healthcare resources. The traditional pessimistic view has been dispelled by results from modern community based prospective studies, showing that over 60% of newly diagnosed patients will enter remission upon treatment. Recent outcome studies suggest that medical intractability may be predicted after failure of two antiepileptic drugs. Poor prognostic factors include a high initial seizure density, symptomatic aetiology, and presence of structural cerebral abnormalities, all of which can be identified early on. Among patients who have entered remission, many will remain seizure-free after antiepileptic drug treatment is withdrawn, suggesting that the underlying seizure generating factor has remitted. Whether some of these patients have entered remission "spontaneously" is contentious because, with effective pharmacotherapy for epilepsy in use for over 100 years, the natural history of untreated epilepsy is largely unknown. Circumstantial evidence, mostly arising from resource poor countries where antiepileptic drug treatment is not readily available, indicates that spontaneous remission may occur in up to 30% of cases. Observations from these complementary sources suggest that, at the population level, prognosis of newly diagnosed epilepsy may be broadly categorised into three groups: remission without treatment, remission with treatment only, and persistent seizures despite treatment. As understanding of the prognostic factors improves, the potential of a "prognostic group specific" management approach should be explored so that effective treatments may be used in a more rational and targeted fashion.

Anticonvulsants↗
PubMed2004

Epilepsy in Hong Kong: a literature review.

OBJECTIVE: To review data on the causes, clinical features, and management of patients with epilepsy in Hong Kong. DATA SOURCES: MEDLINE and Chinese Current Medical Contents were used to search the literature. A manual search of the Hong Kong Medical Journal, Hong Kong Practitioner, and Chinese Medical Journal (1982-2002) was also undertaken. STUDY SELECTION: Key words for the literature search were 'epilepsy' and 'Hong Kong'. DATA EXTRACTION: All relevant articles in English or in Chinese language were reviewed. DATA SYNTHESIS: Overall, disease characteristics and the response to both medical and surgical treatments of epilepsy among local Chinese patients with epilepsy was found to be comparable to that reported for patients in western countries. Knowledge of epilepsy among the general population was more limited than expected from the international literature, and attitudes to epilepsy relatively more negative, adding to the psychosocial burden for people with epilepsy. CONCLUSION: Further research in Hong Kong on aspects of epileptology is indicated with a view to developing more innovative and effective therapy.

Epilepsy↗
PubMed2001

Use of iron oxide-coated sand to remove strontium from simulated Hanford tank wastes.

The ability of iron oxide-coated sand (IOCS) to adsorb strontium from synthetic wastes simulating the tank wastes at the Hanford Nuclear Reservation was examined in this study. These wastes have high pH and high ionic strength, containing up to 5.5 M Na+, 3.7 M NO3-, and 1.2 M OH-. The use of IOCS in such applications may be advantageous because it is inexpensive, is nontoxic, and can be prepared from readily available materials. IOCS can selectively remove strontium from solutions, even when they contain overwhelmingly higher concentrations of potentially competing cations such as Ca2+, Al3+, and Cr3+. Sr-EDTA chelates do not adsorb to IOCS. However, the interference caused by EDTA can be substantially overcome by the addition of excess Ca to the solution since Ca displaces Sr from EDTA. The adsorbed Sr can be released, and the IOCS can be regenerated by exposure to dilute acid (pH approximately 3) for short periods. The physical and adsorptive properties of the IOCS remain essentially unaltered over at least several dozens of regeneration cycles, corresponding to treatment of at least 20000 bed volumes of influent. The only byproduct of the regeneration process is a small volume of residual waste containing essentially only strontium and dilute acid.

Adsorption↗
PubMed2001

Neuropsychological effects of epilepsy and antiepileptic drugs.

Epilepsy and its treatment can have deleterious cognitive and behavioural consequences. Affected individuals have a higher prevalence of neuropsychological dysfunction than the general population because of complex interactions among several multifaceted and overlapping influences--for example, underlying neuropathologies, ictal and interictal neuronal discharges, a plethora of antiepileptic drugs, and numerous psychosocial issues. Research into the clinical relevance of these factors has been dogged by a range of methodological pitfalls including lack of standardisation of neuropsychological tests, small numbers and multiple testing, and statistical failure to appreciate differential effects of interactive elements in individual patients. Although antiepileptic drugs can impair neuropsychological functioning, their positive effect on seizure control might improve cognition and behaviour. Each person should be assessed individually with respect to factors unique to his or her seizure disorder and its treatment.

Anticonvulsants↗
PubMed2001

The mechanisms of action of commonly used antiepileptic drugs.

In the past decade, nine new drugs have been licensed for the treatment of epilepsy. With limited clinical experience of these agents, the mechanisms of action of antiepileptic drugs may be an important criterion in the selection of the most suitable treatment regimens for individual patients. At the cellular level, three basic mechanisms are recognised: modulation of voltage-dependent ion channels, enhancement of inhibitory neurotransmission, and attenuation of excitatory transmission. In this review, we will attempt to introduce the concepts of ion channel and neurotransmitter modulation and, thereafter, group currently used antiepileptic drugs according to their principal mechanisms of action.

Animals↗
PubMed2001

Hormone profiles in young adults with epilepsy treated with sodium valproate or lamotrigine monotherapy.

PURPOSE: Treatment with sodium valproate (VPA) may be associated with polycystic ovarian syndrome (PCOS) in some women with epilepsy. By comparing hormone profiles in young adults taking VPA or lamotrigine (LTG) as monotherapy, this study aimed to explore whether a pharmacologic effect of VPA could be responsible for this observation. METHODS: Hormone profiles in men and women taking VPA (n = 40) or LTG (n = 36) monotherapy for epilepsy were compared. None of the women were receiving hormonal contraception or replacement. Patients gave details of seizure type and frequency, menstrual cycle, and medical and drug history. Body mass index was calculated, and fasting insulin, glucose, cholesterol, triglycerides (TG), high- and low-density lipoproteins, testosterone, dihydroepiandosterone (DHEA), androstenedione, sex hormone-binding globulin (SHBG), free androgen index (FAI), luteinising hormone (LH), follicle-stimulating hormone (FSH), and antiepileptic drug (AED) concentrations were measured. RESULTS: There were no differences between treatment groups for both sexes in age and seizure control. Only four obese VPA-treated women were hyperinsulinaemic (p = 0.05); three with abnormal menstrual cycles; one with raised testosterone. Testosterone (p = 0.02), FAI (p = 0.03), and TG (p = 0.02) levels were higher, however, in women taking the drug. Obese patients of both sexes (p = 0.01) and VPA-treated men (p = 0.03) had higher insulin concentrations. CONCLUSIONS: VPA therapy may be associated with subclinical elevation in fasting insulin levels. Testosterone and TG levels were higher in VPA-treated women compared with the levels in those taking LTG. However, only a minority of obese females exhibited biochemical characteristics suggestive of PCOS. Biochemical screening may allow women at risk of developing PCOS to avoid VPA.

Adult↗
PubMed2001

Effectiveness of first antiepileptic drug.

PURPOSE: To investigate the interaction among efficacy, tolerability, and overall effectiveness of the first antiepileptic drug (AED) in patients with newly diagnosed epilepsy. METHODS: The 470 patients were diagnosed, treated and followed up from January 1984 at a single center. Outcome was classified as seizure freedom for at least the last year or failure of initial treatment because of inadequate seizure control, adverse events, or for other reasons. RESULTS: Overall, 47% of patients became seizure-free with the first prescribed AED. A higher proportion (p = 0.025) of patients with symptomatic or cryptogenic epilepsy changed treatment because of intolerable side effects (17%), and a lower proportion (p = 0.007) became seizure-free (43.5%) compared with those with idiopathic epilepsy (8.5% and 58%, respectively). Most patients (83%) received carbamazepine (CBZ; n = 212), sodium valproate (VPA; n = 101), or lamotrigine (LTG; n = 78). The majority of seizure-free patients required only a moderate daily AED dose (93.1% with < or =800 mg CBZ, 91.3% with < or =1,500 mg VPA, 93.8% with < or =300 mg LTG), with commonest dose ranges being 400-600 mg for CBZ, 600-1,000 mg for VPA, and 125-200 mg for LTG. Most withdrawals due to poor tolerability also occurred at or below these dose levels (CBZ: 98%; VPA: 100%; LTG: 75%). Patients taking CBZ (27%) had a higher incidence of adverse events necessitating a change of treatment than did those treated with VPA (13%) or LTG (10%), resulting in fewer becoming seizure-free (CBZ vs. VPA, p = 0.02; CBZ vs. LTG, p = 0.002). CONCLUSIONS: Nearly 50% of newly diagnosed patients became seizure-free on the first-ever AED, with >90% doing so at moderate or even modest dosing. Tolerability was as important as efficacy in determining overall effectiveness.

Adolescent↗
PubMed2001

Does the cause of localisation-related epilepsy influence the response to antiepileptic drug treatment?

PURPOSE: We investigated the response to antiepileptic drug (AED) therapy in patients with localisation-related epilepsy associated with different underlying causes. METHODS: Five hundred and fifty adolescent and adult patients who had partial epilepsy treated with AEDs and who had undergone magnetic resonance imaging of brain were followed up prospectively from 1984 at a single centre. More than 70% were newly diagnosed. None had had epilepsy surgery. RESULTS: Three hundred and twelve (57%) patients had been seizure free at their last clinic visit for at least a year. Patients with mesial temporal sclerosis (MTS; n = 73, 42% seizure free) were less likely to be controlled (p < 0.01) than were those with arteriovenous malformation (AVM; n = 14, 78%), cerebral infarction (n = 46, 67%), primary tumour (n = 35, 63%), cortical gliosis (n = 81, 57%), cerebral atrophy (n = 49, 55%), and cortical dysplasia (CD; n = 63, 54%). Among the seizure-free patients, those with MTS were more likely to require more than one AED compared with those with other aetiologies (48 vs. 35%; p < 0.05). There was no difference in outcome between patients with symptomatic and cryptogenic epilepsy (n = 361, 58% vs. n = 189, 56% seizure free, respectively). Patients with MTS, CD, and cryptogenic epilepsy were more likely (p = 0.02) to have a family history of epilepsy than were the other groups. MTS patients also had a higher incidence of febrile convulsions (p < 0.001). CONCLUSIONS: The majority of patients with focal-onset epilepsy became seizure free on AED treatment. MTS-related seizures had the worst prognosis. Although many patients with this pathology may benefit from epilepsy surgery, a considerable number will be controlled with AED therapy.

Adolescent↗
PubMed2001

The star systems: overview and use in determining antiepileptic drug choice.

An explosion in antiepileptic drug (AED) therapy began in the 1990s with the licensing of 9 new chemical entities and more to come. Important differences between AEDs may not be detected by regulatory trials, which are designed to satisfy licensing requirements and often diverge considerably from everyday clinical practice. The Star Systems have been developed as evidence-based yet pragmatic and flexible models for comparing AEDs. Each drug has been judged across a range of criteria, including mechanism of action, pharmacokinetics, ease of use, efficacy, tolerability, safety, interaction profile and a 'comfort factor'. A score has been allocated under each category and systems have been devised for patients with newly diagnosed epilepsy and those with difficult-to-control seizures requiring combination therapy. The choice of treatment should involve assessment of patient-related factors, accurate classification of seizure type and syndrome, married with an understanding of the pharmacology of the AEDs. A staged management plan should be formulated when initiating treatment with the aim of preventing the development of refractory epilepsy. When using combinations of AEDs, the mechanism of action of each agent should be taken into consideration. Such an individualised approach to management will optimise the chance of attaining remission and help many more patients achieve a fulfilling life.

Anticonvulsants↗
PubMed2000

Early identification of refractory epilepsy.

BACKGROUND: More than 30 percent of patients with epilepsy have inadequate control of seizures with drug therapy, but why this happens and whether it can be predicted are unknown. We studied the response to antiepileptic drugs in patients with newly diagnosed epilepsy to identify factors associated with subsequent poor control of seizures. METHODS: We prospectively studied 525 patients (age, 9 to 93 years) who were given a diagnosis, treated, and followed up at a single center between 1984 and 1997. Epilepsy was classified as idiopathic (with a presumed genetic basis), symptomatic (resulting from a structural abnormality), or cryptogenic (resulting from an unknown underlying cause). Patients were considered to be seizure-free if they had not had any seizures for at least one year. RESULTS: Among the 525 patients, 333 (63 percent) remained seizure-free during antiepileptic-drug treatment or after treatment was stopped. The prevalence of persistent seizures was higher in patients with symptomatic or cryptogenic epilepsy than in those with idiopathic epilepsy (40 percent vs. 26 percent, P=0.004) and in patients who had had more than 20 seizures before starting treatment than in those who had had fewer (51 percent vs. 29 percent, P<0.001). The seizure-free rate was similar in patients who were treated with a single established drug (67 percent) and patients who were treated with a single new drug (69 percent). Among 470 previously untreated patients, 222 (47 percent) became seizure-free during treatment with their first antiepileptic drug and 67 (14 percent) became seizure-free during treatment with a second or third drug. In 12 patients (3 percent) epilepsy was controlled by treatment with two drugs. Among patients who had no response to the first drug, the percentage who subsequently became seizure-free was smaller (11 percent) when treatment failure was due to lack of efficacy than when it was due to intolerable side effects (41 percent) or an idiosyncratic reaction (55 percent). CONCLUSIONS: Patients who have many seizures before therapy or who have an inadequate response to initial treatment with antiepileptic drugs are likely to have refractory epilepsy.

Adolescent↗
PubMed2000

Glutamic acid decarboxylase autoantibodies in controlled and uncontrolled epilepsy: a pilot study.

There have been anecdotal reports of raised glutamic acid decarboxylase (GAD) autoantibodies in patients with refractory epilepsy. We measured serum GAD autoantibodies in 105 patients with idiopathic or symptomatic epilepsy. There was no significant difference in the absolute titre of GAD autoantibody between patients with controlled and uncontrolled epilepsy. However, four female patients with uncontrolled epilepsy had levels that were over three times above the highest detected in the seizure-free group, three of whom also tested positive for pancreatic islet cell antibodies. Larger scale studies, perhaps comparing different epilepsy syndromes, are required to determine the exact clinical role of GAD autoantibodies in epilepsy.

Adolescent↗
PubMed2000

Epilepsy after the first drug fails: substitution or add-on?

When and how a combination of antiepileptic drugs (AEDs) should be used in patients unresponsive to monotherapy is not known. We followed up prospectively 248 patients in whom treatment with the first AED was unsuccessful. When treatment failed due to intolerable adverse events, a second (substituted) drug was prescribed. When failure was due to lack of efficacy, either AED substitution or combination (add-on) was undertaken. Patients were considered to be seizure-free if they had no seizures for at least 1 year. Among patients with inadequate seizure control on the first well tolerated AED, those who received substituted monotherapy (n= 35) and those who received add-on treatment (n= 42) had similar seizure-free rates (substitution vs. add-on: 17% vs. 26%) and incidence of intolerable side effects (substitution vs. add-on: 26% vs. 12%). Based on the drugs' perceived primary mode of action, more patients became seizure-free when the combination involved a sodium channel blocker and a drug with multiple mechanisms of action (36%) compared to other combinations (7 %, P= 0.05). None of the 11 patients who received add-on treatment after a second drug had also failed became seizure-free, compared to 26% in those who received add-on as soon as the first tolerated AED proved to be ineffective (n= 42, P= 0.05). These preliminary observations have generated verifiable hypotheses regarding the early management of epilepsy. A randomized study comparing substitution and combination after the failure of the first AED is underway.

Anticonvulsants↗
PubMed2000

Randomized, multicenter comparison of oral granisetron and oral ondansetron for emetogenic chemotherapy.

STUDY OBJECTIVES: To compare the antiemetic effectiveness and safety of oral granisetron plus dexamethasone with those of oral ondansetron plus dexamethasone administered before emetogenic chemotherapy. DESIGN: Randomized, prospective, multicenter, open-label study. SETTINGS: University-teaching hospital and veterans health care system. PATIENTS: Sixty-one chemotherapy-naïve patients scheduled to receive emetogenic antineoplastic agents. INTERVENTION: A single-dose oral granisetron 1 mg and dexamethasone 12 mg or single-dose oral ondansetron 16 mg and dexamethasone 12 mg was administered before chemotherapy. MEASUREMENTS AND RESULTS: Twenty-four hours after administration patients were contacted to assess nausea, emesis, and adverse events. There were no statistical differences in frequency of nausea or emesis between groups. Seventy-six percent and 82% of patients receiving ondansetron and granisetron, respectively, experienced no emesis 24 hours after chemotherapy. Complete protection from nausea occurred in 58% and 46% of patients receiving the drugs, respectively. Adverse events were similar between groups. CONCLUSION: Oral granisetron 1 mg and ondansetron 16 mg plus dexamethasone are safe and effective in preventing nausea and vomiting related to emetogenic chemotherapy.

Administration, Oral↗
PubMed1995

Thoracic spinal nerve and root conduction: a magnetic stimulation study.

We describe a technique of magnetic coil (MC) stimulation of the thoracic spinal nerves and roots in 12 normal subjects and a patient with diabetes mellitus. We kept the MC flat against the vertebral column in the midline over T-7, T-8, and T-9 spinous processes and obtained compound muscle action potentials from the upper rectus abdominis, external oblique, and intercostal muscles. We obtained mean latencies to these muscles after stimulation in the posterior axillary line. We noted that the onset latencies remained fixed despite increasing the intensity of stimulation from 30% to 100% and on moving the coil up to 3 cm lateral to the spinous processes suggesting that the stimulation of the fastest conducting fibers was occurring at a fixed site, most likely at the intervertebral foramina. Prolonged latencies in the diabetic patient confirmed the diagnosis of radiculoneuropathy.

Adult↗