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This study investigated the sex differences, and the shared genetic and environmental factors underlying the associations of sleep disturbances (insomnia and sleep quality) with pain and somatic symptoms in both adolescents and middle-aged adults. We recruited 259 adolescents (69 with current insomnia) and their parents (256 middle-aged adults, 78 with current insomnia). Insomnia severity and sleep quality were measured by the Insomnia Severity Inventory (ISI) and Pittsburgh Sleep Quality Index (PSQI), respectively. Pain and somatic symptoms were measured by the Somatic Symptom Inventory and Visual Analogue Scale for overall pain. Subjects with insomnia scored higher on all measures of pain and somatic symptoms than non-insomnia patients, in both adolescents and adults (P<.001). Both pain and somatic measures were associated with ISI and PSQI scores after controlling for age, sex, depressive and anxiety symptoms. There was an interaction effect between insomnia and female sex on pain and somatic symptoms (P<.05), especially in adults. Pain and somatic symptoms ran in family with moderate heritability (range h(2)=0.15-0.42). The phenotypic associations of ISI and PSQI with pain and somatic measures were both contributed by genetic (range p(G)=0.41-0.96) and environmental (range p(E)=0.27-0.40) factors with a major genetic contribution. In summary, insomnia and poor sleep quality are closely associated with pain and somatic symptoms. Insomnia seems to modulate the sex differences in pain and somatic symptoms, especially in the adult population. A shared genetic predisposition might underlie the associations of insomnia and sleep quality with pain and somatic symptoms., (Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Objectives: To determine the familial aggregation of narcolepsy from perspectives of clinical symptomatology, polysomnographic data, and human leukocyte antigen (HLA) typing., Methods: This was a Family study at the University-affiliated hospital. The participants were narcolepsy probands and their first degree relatives, and, also, age and sex matched unrelated healthy controls. Interventions were not applicable., Measurements and Results: All study subjects underwent structured interviews, overnight polysomnography followed by a multiple sleep latency test (MSLT), and HLA typing. Altogether, 33 probands and 81 first degree relatives (response rate 65%) were recruited. Among the relatives, 12.3% were diagnosed with narcolepsy and 39.5% had narcolepsy spectrum as defined by unexplained abnormal MSLT (shortened MSL and SOREMP) results. The relative risk of narcolepsy in first degree relatives was 361.8. Familial aggregation of narcolepsy symptoms, excessive daytime sleepiness, HLA status, abnormal MSLT, and nocturnal polysomnographic findings were observed., Conclusions: The familial risk of narcolepsy among first degree relatives is much higher than previously reported. There exists a spectrum of narcolepsy features among relatives, ranging from full clinical tetrads to asymptomatic abnormal MSLT findings., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objectives: There are limited data on the long-term outcome of childhood insomnia. We explored the longitudinal course, predictors, and impact of childhood insomnia in a community-based cohort., Design: 5-year prospective follow-up., Setting: Community-based., Participants: 611 children (49% boys) aged 9.0 ± 1.8 years at baseline; 13.7 ± 1.8 years at follow-up., Intervention: NA., Main Exposures: Chronic insomnia was defined as difficulty initiating sleep, difficulty maintaining sleep and/or early morning awakening ≥ 3 times/week in the past 12 months., Outcome Measures: General health, upper airway inflammatory diseases, and behavioral problems in recent one year were assessed at both time points, while mental health and lifestyle practice were assessed at follow-up study. The questionnaires at baseline and follow-up were reported by parents/caretakers and adolescents themselves, respectively., Results: The prevalence of chronic insomnia was 4.2% and 6.6% for baseline and follow-up, respectively. The incidence and persistence rates of chronic insomnia were 6.2% and 14.9%, respectively. New incidence of insomnia was associated with lower paternal education level, baseline factors of frequent temper outbursts and daytime fatigue as well as alcohol use and poor mental health at follow-up. Baseline chronic medical disorders, frequent temper outbursts, and poor mental health at follow-up were associated with the persistence of insomnia in adolescents. Baseline insomnia was associated with frequent episodes of laryngopharyngitis and lifestyle practice (coffee and smoking) at follow-up., Conclusions: Chronic insomnia is a common problem with moderate persistent rate in children. The associations of adverse physical and mental health consequences with maladaptive lifestyle coping (smoking and alcohol) argue for rigorous intervention of childhood insomnia.

Introduction: The association between sleep duration, obesity, and serum lipid profile in the youth population is under-explored., Objective: To evaluate the association between sleep duration, obesity and serum lipid profile in the youth population., Methods: We conducted a cross-sectional population-based study with students recruited from primary and secondary schools in Hong Kong. Anthropometric measurements, fasting lipid profiles and validated questionnaires on sleep duration were performed. A subgroup (n=138) was randomly selected for both questionnaires and actigraphy to assess the agreement between subjective and objective measurements of sleep duration., Results: We studied 2053 healthy children and adolescents aged 6-20 years. Their mean ages were 13.0±3.3 (boys) and 13.6±3.3 (girls) years. The average sleep duration during schooldays, weekends, and long holidays was 8.0±1.1, 9.6±1.2, and 9.8±1.2h in boys and 7.7±1.1, 9.9±1.2, and 10.1±1.2h in girls, respectively. Using logistic regression, age, and pubertal stage were associated with obesity in secondary school students, whereas male gender and short sleep duration were associated with obesity in primary school children. In secondary school children, those with long sleep duration, as compared to those with short sleep duration, were significantly associated with reduced risk to have high TC and LDL-C levels after adjustment for age, gender, BMI, and pubertal stage. There was no significant association between sleep duration and lipid levels in primary school children., Conclusion: Reduced sleep duration was associated with obesity and atherogenic dyslipidemia in young school children in Hong Kong., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objectives: The relationship between REM sleep behavior disorder (RBD) and obstructive sleep apnea (OSA) remains unclear. We aimed to (1) explore the association of REM-related EMG activity (REMREEA) with OSA in RBD patients; (2) compare the severity of OSA between RBD patients with OSA (RBD-OSA) and their age-, sex-, AHI-, and BMI- matched OSA controls., Design: a. Correlation study in consecutive RBD subjects and b. case-control study, Setting: Sleep laboratory, Participants: 71 RBD patients in the correlation study and 55 subjects (28 RBD-OSA cases and 27 OSA controls) in the case-control study., Intervention: N/A METHODS: Polysomnographic assessment to document the sleep architecture, sleep apnea related parameters, and REMREEA., Results: (1) In the correlation study, increased REMREEA was associated with lower severity of OSA in RBD patients, including total AHI (r = -0.263), NREM AHI (r = -0.242), obstructive AHI (r = -0.265), and mean apnea duration (r = -0.353) (P < 0.05). (2) In the case-control study, RBD-OSA patients had lesser severity of sleep apnea parameters than OSA controls in terms of higher nadir SpO(2) (85.7% ± 4.9% vs 80.8% ± 5.9%, P < 0.01), shorter maximum hypopnea duration (53.8 ± 16.7 vs 69.4 ± 22.4 seconds, P < 0.05), and maximum (45.8 ± 20.5 vs 60.8 ± 19.6 sec, P < 0.01) and mean apnea duration (22.3 ± 8.1 vs 26.3 ± 5.8 sec, P < 0.05). Significant interaction effects indicated that the usual REM sleep exacerbation of sleep apneas was seen only in OSA controls but not in RBD subjects., Conclusions: This study demonstrated that excessive EMG activity in RBD might protect patients against severe OSA and suggests this may be a naturalistic model for understanding neuromuscular control of OSA.

Objective: The reported prevalence of psychiatric morbidity in chronic pain patients (CCPs) was high, although it varied tremendously since structured diagnostic instruments were seldom used for diagnosis in previous studies. Study in this area after the launching of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) was scarce. This study serves to estimate the prevalence of psychiatric morbidity in patients attending a chronic pain clinic by using the Structured Clinical Interview for DSM-IV (SCID) Axis I disorders and to identify factors highly associated with psychiatric disorders, particularly depression, which is treatable., Method: Consecutive patients attending a chronic pain clinic were recruited during a 6-month period. Psychiatric diagnoses were made by using the SCID. Logistic regression was used to identify factors predicting overall psychiatric morbidity and depression., Results: Prevalence of psychiatric disorders in this 89-patient sample was 62.9%. Current major depressive disorder was present in 31.5% and somatoform disorders in 33.7%. Anxiety disorders and current substance use disorders each constituted 18. "Younger age of onset of pain" (odds ratio [OR]=0.956, P<.05) and "higher pain intensity" (OR=1.544, P<.001) were independently associated with presence of psychiatric disorders. "Higher pain intensity" (OR=13.7, P<.05), "negative pain cognition" (OR=0.967, P<.05) and "problems with social and leisure activities" (OR=38.5, P<.05) were associated with depression., Conclusion: Prevalence of psychiatric disorders in this Chinese chronic pain clinic sample with reference to the DSM-IV was similar to that reported in previous studies. Specific factors were identified to alert pain physicians to underlying psychiatric disorders., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objective: To validate a Chinese version of the Diabetes Distress Scale (CDDS)., Research Design and Methods: The CDDS was derived using forward-backward translation and administered in 189 Chinese type 2 diabetic patients with evaluation of its psychometric properties., Results: On the basis of principal-component analysis, three factors of the 15-item version of the CDDS (CDDS-15) accounted for 63% of the variance. The correlation coefficient between the original 17-item and 15-item scales was 0.99. The Cronbach α for internal consistency was 0.90, and the test-retest reliability coefficient was 0.74. The CDDS-15 score was significantly associated with glycemic control, obesity, depressive symptoms, and quality of life., Conclusions: The CDDS-15 is a valid and reliable instrument to assess diabetes-related distress.

Study Objectives: To conduct a systematic investigation on the prevalence, correlates, and familial aggregation of frequent nightmares in children, and to scrutinize the associations between frequent nightmares and parent-reported behavioral and mood problems in children., Design: A cross-sectional study was conducted by collecting the data on sociodemographic, sleep, behavioral, and family-related information from a total of 6359 children (age: mean [SD]=9.2 [1.8] years; girls: 49.9%) and their reported biological parents., Setting: Community., Interventions: N/A., Measurements and Results: Prevalence of frequent nightmares with a criterion of at least once per week was 5.2%. Multinomial regression analysis indicated that monthly family income, paternal and maternal nightmares, insomnia symptoms, parasomniac symptoms, and daytime consequences were significantly associated with nightmares in children. Frequent nightmares in children were significantly associated with hyper-activity (odds ratio [OR]=1.68, 95% CI 1.16-2.44), frequent temper outbursts/mood disturbance (OR=1.76, 95%CI 1.27-2.44), and poor academic performance (OR=1.62, 95% CI 1.11-2.36), after controlling for potential confounding factors. Approximately 20% of children with frequent nightmares experienced comorbid frequent insomnia. Comorbid nightmares and insomnia were associated with increased odds of hyperactivity (OR=4.13, 95% CI 2.13-8.00) and frequent temper outbursts/mood disturbance (OR=2.41, 95%CI 1.27-4.60)., Conclusions: Frequent nightmares in children are associated with a constellation of child-, sleep-, and family-related factors, including comorbid sleep problems, such as insomnia and parasomnia, family economic status, and parental predisposition. Frequent nightmares are independently associated with emotional and behavioral problems in children.

Objectives: a. Explore the stability in sleep/wake patterns of middle-aged adults over a 3-year follow-up period. b. Explore the relationship between objectively measured sleep indices, urinary catecholamines, and salivary cortisol., Design: Naturalistic follow-up for sleep/wake patterns (n = 114) by 2-week sleep log and cross-sectional design for objective sleep assessments and hormonal measures (n = 96) at follow-up period nearly 3 years after baseline measurements., Setting: Community, Participants: Healthy middle-aged adults, Interventions: N/A., Measurements and Results: There were high correlations between baseline and follow-up period (2.6 ± 0.5 years) on sleep/wake patterns (r = 0.6-0.79) as measured by 2-week sleep log. For wave 2 cross-sectional study, objective poor sleepers (3-day actigraphy sleep efficiency < 85%) had a higher 24-h urinary norepinephrine (NE) level (205.7 ± 105 nmol/d vs 162.1 ± 55.6 nmol/d, P = 0.03) and a nearly significantly higher 24-h urinary epinephrine (E) level (P = 0.12) than good sleepers. There were no differences in 3-day mean salivary awakening cortisol and 24-h urinary catecholamines (NE and E) between short and normal/long sleepers. Linear regression results, however, showed that shorter time in bed and actual sleep time, longer sleep onset latency, and lower sleep efficiency were correlated with higher 24-h urinary E and NE (all P < 0.05) but not salivary cortisol. The effect of poor sleep quality on 24-h urinary catecholamines was stronger in males than females., Conclusions: Increased sympathetic activity as measured by 24-h urinary catecholamines might play a critical role in the pathogenesis mediating the relationship of insufficient sleep (quantity and quality) with subsequent cardiovascular and metabolic complications. Salivary awakening cortisol was not associated with sleep quantity and quality in healthy middle-aged adults.

Obstructive sleep apnea (OSA) is a common sleep and breathing disorder characterized by repeated episodes of hypoxemia. OSA causes neurocognitive deficits including perception and memory impairment but the underlying mechanisms are unknown. Here we show that in a mouse model of OSA, chronic intermittent hypoxia treatment impairs both early- and late-phase long-term potentiation (LTP) in the hippocampus. In intermittent hypoxia-treated mice the excitability of CA1 neurons was reduced and hippocampal brain-derived neurotrophic factor (BDNF) was down-regulated. We further showed that exogenous application of BDNF restored the magnitude of LTP in hippocampal slices from hypoxia-treated mice. In addition, microinjection of BDNF into the brain of the hypoxic mice prevented the impairment in LTP. These data suggest that intermittent hypoxia impairs hippocampal neuronal excitability and reduces the expression of BDNF leading to deficits in LTP and memory formation. Thus, BDNF level may be a novel therapeutic target for alleviating OSA-induced neurocognitive deficits., ((c) 2010 Elsevier Inc. All rights reserved.)

Study Objectives: To determine the prevalence of frequent nightmares and their correlates in a large community-based cohort of middle-aged Hong Kong Chinese., Design: A 2-phase design involving a cross-sectional survey of 8558 subjects (men, 47.6%) with a mean age of 40.9 years (SD 5.5, range 20-78) and subsequently followed by a detailed clinical evaluation of the psychopathology and personality profile of 252 subjects., Setting: Community., Interventions: N/A., Measurements and Results: The prevalence of frequent nightmares, as defined by at least once per week, was 5.1%. Female sex, low monthly family income, insomnia symptoms, sleep-disordered breathing symptoms, and sleep-related daytime consequences were significantly associated with nightmare frequency. The risk of having a psychiatric disorder was 5.74 times greater for subjects with frequent nightmares (95% confidence interval 2.03-16.26), especially mood disorders (odds ratio = 15.57, 95% confidence interval 3.77-64.37). After exclusion of concomitant psychiatric morbidities, subjects with frequent nightmares still scored significantly higher on neuroticism in the personality scale (p < 0.05)., Conclusions: Frequent nightmares were not uncommon in the general population and were associated with a constellation of factors, including sociodemographic characteristics and comorbid sleep and psychiatric disorders. Moreover, frequent nightmares were independently related to the neuroticism personality trait, irrespective of psychiatric diagnosis. Prospective studies should be conducted to investigate various predisposing, precipitating, and perpetuating factors and the associated repercussions of nightmares.

Background: Increasing evidence suggests that blood pressure (BP) is significantly influenced by sleep problems in children, but the association between periodic limb movement during sleep (PLMS) and BP is still unclear. This study aims to compare ambulatory blood pressure (ABP) in children with and without PLMS., Methods and Results: A cross-sectional study involving 314 children (mean (SD) age of 10.4 (1.7) years, boys 62.4%). Participants underwent an overnight polysomnographic study and ABP monitoring. Subjects were hypertensive if mean SBP or DBP > 95th percentile and prehypertensive if mean SBP or DBP > 90th percentile of reference. Children with PLMS (n = 17) were at significantly higher risk for nocturnal systolic (adjusted OR (95%CI) = 6.25 [1.87-20.88]) and diastolic (OR (95%CI) = 4.83 [1.66-14.07]) hypertension. However, mean nocturnal BP did not differ between children with and without PLMS. There was a trend for higher daytime BP in patients with PLMS than those children without PLMS (P = 0.084 for systolic BP z score; P = 0.051 for diastolic BP z score; P = 0.067 for systolic prehypertension). There were significant associations between log transformed PLM index and daytime systolic and mean BP z scores (P = 0.03 and 0.033 respectively) as well as that between log transformed PLM related arousal index (PLMSArI) and nocturnal diastolic and mean BP (P = 0.008 and 0.038 respectively)., Conclusions: PLMS was independently associated with a wide range of BP elevations, especially nocturnal indices. Future studies should examine the underlying pathophysiologic mechanisms and effects of PLMS treatment on BP.

Objectives: To determine sleep/wake patterns of primary school children and their correlates., Study Design: A total of 4470 sets of mother-father-child community-based trios were recruited in this study. We constructed 3 integrated models with structural equation modeling to predict sleep/wake patterns of children (bedtime, wakeup time, and time in bed [TIB])., Results: Our best-fitting models explained 40% to 71% variances of various sleep/wake patterns of the children, which were influenced by a web of interactive factors including school start time, parental sleep/wake patterns, sociodemographics, and daytime activities. The strongest predictor of various sleep/wake patterns was school start time. Higher socioeconomic status would shorten TIB of both children and parents, but through different pathways (by advancing wakeup time and delaying bedtime in children but by delaying bedtime in parents). Media use and homework shortened TIB of children, while leisure extracurricular activities and later school start time lengthened it. The age and sex effects on sleep/wake patterns, at least in part, were mediated by daytime activities. Daytime activities of children also influenced their parental sleep/wake patterns, especially their maternal one. A consistent pattern of stronger mother-child than father-child associations were found in various sleep/wake patterns., Conclusions: There was a complex and interactive relationship among school schedule, parental sleep/wake patterns, socioeconomic status, and daytime activities in determining the sleep/wake patterns of children. These findings have important clinical implications for the management of childhood sleep/wake habits and problems., (Copyright 2010 Mosby, Inc. All rights reserved.)

Objective: To determine the reproducibility of the Brodsky grading scale and the modified 3-grade and 5-grade scales in reporting the size of the tonsils., Design: Retrospective review of 60 video recordings of tonsil examination by 12 independent observers with different clinical backgrounds and various levels of training. The sizes of the tonsils were graded using different grading scales., Setting: Tertiary care university hospital., Participants: The video recordings were chosen from an ongoing epidemiologic study of sleep-related breathing disorder in children in Hong Kong. Main Outcomes Measures The intraobserver and interobserver reproducibility of each grading scale was determined using intraclass correlation. An intraclass correlation coefficient (ICC) exceeding 0.75 was set a priori to indicate an acceptable level of reliability., Results: The mean intraobserver ICCs for the Brodsky grading scale and the modified 3-grade and 5-grade scales were 0.858, 0.830, and 0.865, respectively. The mean interobserver ICCs for the Brodsky grading scale and the modified 3-grade and 5-grade scales were 0.763, 0.739, and 0.783, respectively., Conclusion: The Brodsky grading scale and the modified 5-grade scale achieved acceptable intraobserver and interobserver reproducibility.

Background: Short-term follow-up studies of severe acute respiratory syndrome (SARS) survivors suggested that their physical conditions continuously improved in the first year but that their mental health did not. We investigated long-term psychiatric morbidities and chronic fatigue among SARS survivors., Methods: All SARS survivors from the hospitals of a local region in Hong Kong were assessed by a constellation of psychometric questionnaires and a semistructured clinical interview for the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) to determine the presence of psychiatric disorders and chronic fatigue problems., Results: Of 369 SARS survivors, 233 (63.1%) participated in the study (mean period of time after SARS, 41.3 months). Over 40% of the respondents had active psychiatric illnesses, 40.3% reported a chronic fatigue problem, and 27.1% met the modified 1994 Centers for Disease Control and Prevention criteria for chronic fatigue syndrome. Logistic regression analysis suggested that being a health care worker at the time of SARS infection (odds ratio [OR], 3.24; 95% confidence interval [CI], 1.12- 9.39; P = .03), being unemployed at follow-up (OR, 4.71; 95% CI, 1.50-14.78; P = .008), having a perception of social stigmatization (OR, 3.03; 95% CI, 1.20-7.60; P = .02), and having applied to the SARS survivors' fund (OR, 2.92; 95% CI, 1.18-7.22; P = .02) were associated with an increased risk of psychiatric morbidities at follow-up, whereas application to the SARS survivors' fund (OR, 2.64; 95% CI, 1.07-6.51; P = .04) was associated with increased risk of chronic fatigue problems., Conclusions: Psychiatric morbidities and chronic fatigue persisted and continued to be clinically significant among the survivors at the 4-year follow-up. Optimization of the treatment of mental health morbidities by a multidisciplinary approach with a view for long-term rehabilitation, especially targeting psychiatric and fatigue problems and functional and occupational rehabilitation, would be needed.

Objectives: A growing trend in childhood sleep habits is to compensate for the weekday sleep deficit by longer weekend and holiday sleep duration. We aimed to investigate the effect of weekend/holiday sleep compensation in relation to childhood overweight and obesity., Methods: This is a community-based cross-sectional study with 5159 children (49.6% boys), mean age of 9.25 years (SD: 1.78), from 13 primary schools in Hong Kong. Data on sleep patterns, lifestyle, body weight, and height of children were obtained from questionnaires. Sleep durations during weekdays, weekends, and holidays were predictor variables. BMI z scores and obesity/overweight status were the outcome measures., Results: Children slept significantly longer during holidays (mean [SD]: 10.20 (0.92) hours) and weekends (school terms) (10.07 [0.93] hours) than during school weekdays (9.18 [0.95] hours). Children with shorter sleep duration had higher BMI z scores regardless of the sleep parameters used in the analysis. Among children who slept <8 hours during weekdays, those children who did not compensate for their sleep deficit during weekends or holidays had significantly increased risk of overweight/obesity compared with those children with sleep compensation (odds ratios: 2.59 [95% confidence interval: 1.22-5.48] and 2.32 [95% confidence interval: 1.00-5.53], respectively)., Conclusions: There was a prominent difference in sleep duration between weekdays and weekends/holidays among school children. Short sleep duration was associated with higher BMI, but compensation of sleep during weekends/holidays may partly ameliorate the risk of childhood overweight/obesity. Further prospective and interventional study is needed to delineate the risk-benefit effect of these increasingly common sleep habits among children and adolescents.

The 'one pot' condensation reaction for the synthesis and potent antiproliferative inhibition of alpha-phthalimide based ketones is reported here. 2-Phthalimide-1-(4-fluoro-phenyl)ethanone (5) showed the best growth inhibition on human MDAMB-231 breast carcinoma and SKHep-1 hepatoma cell lines. Preliminary studies showed that the reported bioactivity may be due to the presence of strong electronegative fluorine group at the para-position of the aryl ring.

Objectives: In contrast to the 'benign and self-limiting nature' of childhood sleepwalking, some population and case studies have suggested that adult sleepwalking is more likely to be associated with psychopathology and psychotropic medications. There is a paucity, however, of systematic study in adult psychiatric populations, and the aim of the present study was therefore to compare the impact of psychopathology and medication usage on sleepwalking with reference to age of onset., Methods: Clinical characteristics, sleep symptoms, psychiatric diagnosis and psychotropic usage in 66 childhood- and adult-onset sleepwalkers as identified from a psychiatric clinic, were studied., Results: There was a higher proportion of adult-onset sleepwalking in the psychiatric population. In comparison with childhood-onset sleepwalkers, adult-onset sleepwalkers had higher peak frequency of attacks and a high comorbidity with sleep-related eating features. Factors including frequent insomnia (odds ratio (OR) = 5.39, 95% confidence interval (CI) = 1.58-18.40, p = 0.007) and lifetime usage of regular zolpidem (OR = 5.58, 95%CI = 1.65-18.84, p < 0.006) were associated with a higher risk of adult-onset sleepwalking., Conclusions: Adult-onset sleepwalking in a psychiatric sample has unique clinical characteristics and specific risk factors. These patients were more likely to present with sleep-related eating features, comorbid insomnia, had and lifetime usage of non-benzodiazepine hypnotics, especially zolpidem. A heightened awareness of the presence of sleepwalking and their associated risk factors among the adult psychiatric population is needed.

Background: Hypokalemia is an easily identifiable, clinically important but commonly neglected condition in psychiatric patients. This study intended to examine the prevalence of hypokalemia and its clinical correlates in acute psychiatric inpatients., Method: This retrospective study was conducted over a 6 month period in 2008. The case notes, computerized records and laboratory results of all patients who were consecutively admitted to the acute psychiatric wards in a University-affiliated regional psychiatric unit were studied., Result: Three hundred forty-seven patients out of 440 admissions were studied. Hypokalemia, as defined by serum potassium level of less than 3.5 mmol/L, was found in 20.5% of patients with a higher prevalence in psychotic patients (27.7%). The mean potassium level of psychotic patients was lower than that of the overall study population (3.72 vs. 3.81 mmol/L, P<.05). White cell counts among the hypokalemic patients were higher than those without hypokalemia (7.8 vs. 7.1 x 10(9)/L, P=.02)., Conclusion: Hypokalemia was common among acute psychiatric inpatients. Both agitation and the use of antipsychotics were postulated to contribute to the high prevalence of hypokalemia among acutely ill psychiatric patients.

Uterine cervical cancer, the second most frequently occurring cancer in women worldwide, is tightly associated with the expression of high-risk human papillomavirus [mainly human papillomavirus (HPV)-16 and HPV18] oncogenes E6 and E7 and characteristically exhibits chromosomal instability. However, the mechanisms underlying chromosomal instability in cervical cancer are still not fully understood. In this study, we observed that two of three human cervical epithelial cell lines expressing HPV16 E6E7 became immortalized without extensive chromosomal instability and crisis. The introduction of transforming growth factor (TGF)-beta1, a multiple functional cytokine/growth factor, in the culture medium induced crisis, which was associated with massive chromosomal end-to-end fusions and other structural aberrations. The distributions of structural aberrations on individual chromosomes were significantly correlated with the profiles of telomere signal-free ends. The immortalized cells that emerged from the TGF-beta1-induced crisis showed multiple clonal structural aberrations that were not observed in cells without TGF-beta1 treatment. Overexpression of the catalytic subunit of telomerase (hTERT) abolished the effects of TGF-beta1 on chromosomal instability. Interestingly, another HPV16 E6E7-expressing cervical cell line that experienced crisis and telomere dysfunction under ordinary culture condition had a higher level of autocrine TGF-beta1 production than the other two crisis-free immortalized cell lines. Blocking the TGF-beta1 pathway by an inhibitor of TGF-beta1 receptor type I prevented the crisis and telomere-mediated chromosomal instability. In addition, more dramatic telomere shortening was observed in cervical intraepithelial neoplasias having higher expression of TGF-beta1 in vivo. These results together suggest an important role of TGF-beta1 in the early process of cervical carcinogenesis.

Study Objectives: Clinical features of RBD were typically episodic with limited data on the night-to-night reliability of the diagnostic video-PSGs. We aimed to assess on whether a single night study was adequate., Design: Retrospective review., Setting: Sleep laboratory., Participants: 55 RBD patients with at least 2 consecutive video-PSGs., Interventions: N/A., Methods: We analyzed 2 consecutive video-PSGs using REM-related EMG activity (REMREEA), REM sleep without atonia (RSWA), and video analysis of motor events., Measurements and Results: A weak first night effect with increased REM sleep latency, increased stage 1 sleep, and increased arousal index were found. No differences were found in phasic and tonic EMG activity scores between night 1 and night 2. The presence of OSAS, use of CPAP, and clonazepam treatment did not affect the night-to-night variability and diagnostic accuracy. The kappas were 0.64, 0.51, and 0.31 between night 1 and night 2 for 10% REMREEA, RSWA, and video analysis respectively. Over 80% of patients could be diagnosed by various criteria in the first night, but the diagnostic ability could be enhanced to nearly 95% when combining PSG with video analysis. While both of the EMG criteria as well as the combination criteria had good reliability, video-analysis had poorer night-to-night reliability., Conclusions: A single night of video-PSG was adequate in the diagnosis of RBD in most clinical patients and the combination of PSG and video analysis could enhance the detection rate further. Our findings have important resource implications.

Objective: Insomnia could be a symptom of underlying psychiatric or physical disorder, a risk factor for other psychiatric disorder, or a discrete psychiatric disorder per se. In order to determine the nosological status of primary insomnia, an outcome study was carried out to investigate its diagnostic stability and its relationship to subsequent psychiatric disorders., Methods: Fifty-three primary insomnia patients in a university hospital psychiatric outpatient clinic were assessed by retrospective case note review, followed by a 6 month prospective follow up with Structured Clinical Interview Schedule for DSM-IV In-patient (SCID-I/P, version 2.0, and a sleep questionnaire., Results: The majority of patients (n =44, 83%) did not develop other psychiatric disorders after 13.4+/-1.2 years from the onset of insomnia. Nine patients (17%) developed mood disorder (n =6), anxiety disorder (n =2) and somatoform disorder (n =1) at 6.3+/-2.3 years after the onset of insomnia. Subjective deterioration of insomnia and a shorter duration of sleep symptoms at the first consultation were associated with the development of secondary psychiatric disorders. Approximately one-third (n =17, 32%) reported symptoms improvement and six (13.2%) were free from medications. Better education was the only factor that predicted improvement in symptoms., Conclusions: There existed a longitudinal diagnostic stability of primary insomnia in a majority of clinical patients. However, in a proportion of patients, it might either be a risk factor or a prodrome of mood or anxiety disorders.

Study Objectives: To explore the familial aggregation and HLA susceptibility of narcolepsy in Hong Kong Chinese by objective sleep measurements and HLA typing., Design: Case control design, Participants: Twelve narcoleptic probands, 34 first-degree relatives, and 30 healthy controls., Interventions: N/A., Measurements and Results: Each subject underwent a standardized nocturnal polysomnogram (PSG), followed by a daytime multiple sleep latency test (MSLT). HLA typing was performed for all subjects. One relative (2.9%) was diagnosed as suffering from narcolepsy with cataplexy. Nearly 30% of the relatives fulfilled the criteria of narcolepsy spectrum disorder (shortened mean sleep latency [MSL] and/or the presence of sleep onset REM periods [SOREMPs]). When using the population data for comparison, the relative risk of narcolepsy in first-degree relatives was 85.3. The odds ratio of narcolepsy spectrum disorder in first-degree relatives was 5.8 (95% CI: 1.2 - 29.3) when compared to healthy controls. There existed 6 multiplex families, in which all 10 relatives with narcolepsy spectrum disorders, including all 3 relatives with multiple SOREMPs, were positive for HLA DQB1*0602., Conclusions: Our study demonstrated a definitive familial aggregation of narcolepsy, narcolepsy spectrum disorders, and possibly cataplexy in Hong Kong Chinese. This familial aggregation supported an inherited basis for narcolepsy spectrum. The tight co-segregation of HLA DQB1*0602 and narcolepsy spectrum disorders might suggest that HLA typing, especially DQB1*0602, at least partly confer the familial risk of narcolepsy. In addition, our study suggested that the subjective questionnaire measurements including Ullanlinna Narcolepsy Scale and Epworth Sleepiness Scale were unable to detect the presence of narcolepsy spectrum disorders among the relatives. A stringent objective measurement-based design for family studies is suggested for future study. Further studies are indicated for the determination of the mode and molecular level of narcolepsy transmission.

Umbilical cord blood is a valuable source of haemopoietic stem/progenitor cells (HSC) for transplantation. This study explored the effect of maternal plasma/human serum albumin (HSA) in the purification and culture conditions of CD34+ cells derived from human umbilical cord blood. During CD34+ cell enrichment, including maternal plasma or HSA instead of fetal bovine serum (FBS) in the wash buffer, significantly increased the purity and the fold expansion of CD34+ cells. The increase in fold expansion of CD34+ cells was independent of CD34+ cell purity before expansion. With FBS, the mean fold expansion of CD34+ cells and total nucleated cells on day 7 was 9.7 +/- 5.5 and 39.7 +/- 13.7 respectively. The use of maternal plasma increased the mean fold expansion of CD34+ cells and total nucleated cells on day 7 to 28.2 +/- 6.7 and 71.5 +/- 15.4 respectively. When HSA was added to wash buffer, the mean fold expansion of CD34+ cells and total nucleated cells were 30.4 +/- 10.5 and 83.5 +/- 24.8 respectively. No statistical significance was found between using HSA and maternal plasma on total cell and CD34+ cell expansion. We propose that HSA in maternal plasma was responsible for the positive effect on CD34+ cell enrichment and expansion.

Objective: Comparative genomic hybridization has frequently detected amplification of chromosome 5p in cervical cancer, but candidate cancer genes within the region are rarely known. Therefore, we pursued to identify potential candidate gene related to cervical cancer development., Methods: A series of 128 cervical tumor samples were examined by semi-quantitative fluorescent differential PCR for copy number changes on three candidate genes (PRKAA1, CTNND2 and POLS) mapped to chromosome 5p and one gene (ERBIN) mapped to chromosome 5q12.3. The impact of gene copy number was later analyzed in relation to HPV infection, tumor stage or tumor radiosensitivity., Results: DNA copy numbers of PRKAA1, CTNND2 and ERBIN were significantly different from normal controls (P < 0.05). DNA copy number changes did not correlate with HPV infection, tumor stages or tumor radiosensitivity. Using RT-PCR, PRKAA1 mRNA expression in seven tumor samples with known 5p amplification was amplified from 3- to 15-fold. Over-expression of PRKAA1 was further confirmed by immunohistochemical staining on 125 paraffin-embedded cervical cancer tissues. The expression level in cervical tumor was significantly higher than that in normal epithelium (P < 0.001)., Conclusions: PRKAA1 gene codes for the catalytic alpha 1 subunit of the AMP-activated protein kinase which is an important cellular metabolic stress regulator. It might assist tumor cells growth under stress. Thus, PRKAA1 may be one of the potential candidate genes for cervical carcinogenesis.

Objectives: To investigate 2 positive impacts (better family/social support and lifestyle changes) and their associations with other negative impacts., Study Design and Participants: A telephone survey using random telephone numbers and a structured questionnaire was conducted in Hong Kong general population. Eight hundred and eighteen Hong Kong residents of age 18-60 years completed the interview (response rate: 65%) at around end of June 2003, the early ending phase of the epidemic., Results: Over 60% of the respondents stated that they cared more about the family members' feelings; about 30%-40% stated that they found their friends, their family members more supportive or having more sharing with others when not feeling happy; only a few percent felt the opposite. Further, about 2/3 of the respondents paid more attention to their mental health. About 35%-40% took more time to rest, for relaxation or doing exercise. These items were, in general, negatively associated with post-traumatic stress, perception of stress and other perceptions that were related to SARS., Conclusions: SARS have brought some positive impacts on social/family support, mental health awareness and lifestyle changes. These positive impacts were associated with other relevant negative impacts and might be important cushions of the negative impact.

Although the relationship of CYP2C19 polymorphism to citalopram disposition has been studied in healthy subject, this relationship in combination with dynamic effects (clinical adverse effect of citalopram) has not been well studied in patients. We carried out the present study to investigate the CYP2C19 genotype-phenotype relationship and potentially relate such relationship to the clinical effect (specifically adverse effects) of citalopram in Chinese patients who are known to have relatively high prevalence of poor metabolizers (PMs) of CYP2C19. Fifty-three Chinese adult patients were recruited. One to 2 blood samples at 4 to 24 hours postdose were collected after a minimum of 2 weeks of citalopram administration. The CYP2C19 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism, and the plasma concentrations of citalopram and desmethylcitalopram were determined by a liquid chromatography-tandem mass spectrometry method. The clinical adverse effects associated with citalopram were assessed according to Toronto Side Effects Scale (TSES). A population pharmacokinetic model was used to analyze the citalopram concentrations. Among 53 patients, 21 were homozygous extensive metabolizers (EMs) (CYP2C19*1/*1), 25 heterozygous EMs (CYP2C19*1/*2 or *1/*3), and 7 PMs (CYP2C19*2/*2 or *2/*3 or *3/*3). The metabolic ratios (plasma concentration of desmethylcitalopram to citalopram) were found to be 0.20 +/- 0.07, 0.15 +/- 0.05, and 0.07 +/- 0.03 in the homozygous EMs, heterozygous EMs, and PMs, respectively (P < 0.001, 1-way analysis of variance). On the basis of the results from our population pharmacokinetic modeling analysis, the citalopram oral clearances in the PMs were 42.9% and 33.3% (both P < 0.05) lower compared with the homozygous and heterozygous EMs, respectively. Statistically significant correlation was observed between the oral clearance and TSES scores in individual patients (rs = -0.37, P = 0.012). The mean TSES score also tended to be higher in PM than EM patients, but the difference was not statistically significant (P = 0.234). The study demonstrated a significant CYP2C19 genotype-phenotype relationship in Chinese patients receiving citalopram treatment. Such a relationship also tended to correlate with the clinical adverse effects of the drug. These results provide important pharmacogenetic implications for citalopram therapy in the Chinese population in whom relatively high frequency of CYP2C19 PM phenotype exists.

This study aimed to investigate the prevalence of sleep problems in Chinese children with pervasive developmental disorders (PDD) in Hong Kong and their relationship to parental stress. A cross-sectional survey was conducted in six child assessment centres. All parents of the children with PDD completed the Children's Sleep Habits Questionnaire, the Parenting Stress Index-Short Form, and questions on sleep practice. A total of 210 out of 250 questionnaires (response rate 84%) were returned. Mean age of the children was 3 years 6 months (SD 1 y 4 mo; range 2 y-7 y 7 mo; 168 males, 25 females). The prevalence of parent-defined sleep problems in various sleep domains ranged from 9.3 to 45.6%, with 67.9% of children having significant problems in at least one sleep domain. The most common problems reported were bedtime resistance and parasomnias. Similar sleep problems occurred in all the PDD subgroups. The factor most significantly associated with sleep problems was the occurrence of sleep problems before the age of 2 years. The parents of children with PDD with sleep problems experienced a higher level of stress than those whose children had no sleep problems. A high prevalence of significant sleep problems was reported in Chinese children in Hong Kong with PDD. A higher stress level among the parents of those children with PDD with sleep problems suggests the need for systematic early detection and management of sleep problems in children with PDD.

Objectives: To identify the extra chromosomal material on 46,XX,21p+ for prenatal diagnosis., Design and Methods: Conventional cytogenetic studies using GTG (G bands by trypsin using Giemsa) and CBG (C bands by barium hydroxide using Giemsa) techniques were performed on chromosomes at metaphase obtained from cultured amniocytes and parental blood lymphocytes. Molecular cytogenetic techniques, QF-PCR (quantitative fluorescent polymerase chain reaction), FISH (fluorescent in-situ hybridization), and DA-DAPI (Distamycin A and 4,6-diamino-2-phenylindole) staining, were then used to clarify the extra material present on fetal chromosome 21 p., Results: The extra material on fetal chromosome 21 p has originated from Yqh, most likely at PAR2 (the secondary pseudoautosomal region). The karyotype should be 46,XX,der(21)t(Y;21)(q12;p13)de novo.ish der(21)t(Y;21)(q12;p13) (EST Cdy16c07+)., Conclusion: This case demonstrates the usefulness of molecular techniques in the investigation of rare chromosomal rearrangements.

Study Objective: Most but not all epidemiologic evidence suggests a female predisposition of insomnia. We applied meta-analytic methods to investigate sex differences in the risk of insomnia among the published epidemiologic studies., Design: Meta-analysis with Comprehensive Meta-Analysis (Englewood, NJ); 9 different analyses were performed to investigate the sex difference of insomnia among different conditions., Setting: A comprehensive search of the medical literature databases was performed to identify epidemiologic studies of insomnia. A rolling snowball method was also used., Participants: General population., Interventions: N/A., Result: Thirty-one related papers were found, but 2 studies only reported the subtype prevalence of insomnia. All other studies (1,265,015 participants, female/male: 718,828/546,187) were included in the overall analysis of insomnia. A risk ratio of 1.41 [95% confidence interval: 1.28-1.55] for female versus male was found. The female excess in the risk of insomnia in large and quality studies was much higher than that of small and nonquality studies. The trend of female predisposition was consistent and progressive across age, with more significance in the elderly. The use of various criteria and frequency and duration of insomnia did not influence the predisposition of female in the risk of developing insomnia. Although obvious female excess in the risk of insomnia exists among different regions, there was a relatively lower female excess in East Asia., Conclusion: This meta-analysis confirmed a female predisposition of insomnia. Further studies will be needed to examine the roles of different factors in leading to the sex difference of insomnia.

To understand different aspects of community responses related to severe acute respiratory syndrome (SARS), 2 population-based, random telephone surveys were conducted in June 2003 and January 2004 in Hong Kong. More than 70% of respondents would avoid visiting hospitals or mainland China to avoid contracting SARS. Most respondents believed that SARS could be transmitted through droplets, fomites, sewage, and animals. More than 90% believed that public health measures were efficacious means of prevention; 40.4% believed that SARS would resurge in Hong Kong; and approximately equals 70% would then wear masks in public places. High percentages of respondents felt helpless, horrified, and apprehensive because of SARS. Approximately 16% showed signs of posttraumatic symptoms, and approximately equals 40% perceived increased stress in family or work settings. The general public in Hong Kong has been very vigilant about SARS but needs to be more psychologically prepared to face a resurgence of the epidemic.

Objective: To investigate a simple non-invasive technique for early detection of Hemoglobin (Hb) Bart's disease., Method: Maternal blood smears from 8 known Hb Bart's pregnancies and 40 at-risk pregnancies were investigated. Maternal peripheral blood smears were stained with fluorescence-labeled monoclonal antibodies against alpha- and embryonic zeta-globin chains., Results: Fetal nonnucleated red blood cells, stained with anti-zeta but not with anti-alpha globin antibodies were found in 15 out of 16 affected pregnancies but were not detected in 23 out of 24 unaffected pregnancies., Conclusion: Results showed that non-invasive immunofluorescence staining of maternal blood is a feasible approach for screening Hb Bart's disease before ultrasound manifestation in affected pregnancies., (Copyright 2005 John Wiley & Sons, Ltd.)

Cervical and vulvar cancers are diseases of the female lower genital tract, and high-risk human papillomavirus (HPV) infection is the most important risk factor for the development of both cancers. However, it is clear that additional genetic events are necessary for tumor progression, particularly in HPV-negative cases. We detected the presence of high-risk HPV16 and HPV18 genomes by gene-specific polymerase chain reaction and searched for common genetic imbalances by comparative genomic hybridization (CGH) in 28 cervical and 8 vulvar tumor samples and 7 cancer cell lines. The presence of the HPV genome was detected in 25/28 (89%) cervical tumors and 6/8 (75%) vulvar tumors. CGH of cervical and vulvar tumor samples revealed a consistent pattern of genetic changes in both cancers. Frequent gains were found in 1q, 3q, 5p, and 8q, and less consistent losses were detected in 2q, 3p, 4p, and 11p. Notably, a high-level amplification of 3q was found in 9/28 (32%) cervical tumors and 1/8 (12.5%) vulvar tumors, indicating a pivotal role of gain of 3q in cervical and vulvar carcinogenesis. Furthermore, gains of 5p identified in 9/28 (32%) cervical tumors and 3/8 (37.5%) vulvar tumors were seldom described, particularly in vulvar tumors. Our findings suggest that cervical and vulvar carcinomas bear similar chromosomal alteration hot spots that largely coincide with common genomic lesions during tumor progression, besides the initiation by infection and integration of oncogenic HPV.

This study aimed to examine the short-term adjustment outcomes including distress, self-esteem, and quality of life among Chinese patients after 1-month recovery from severe acute respiratory syndrome (SARS) in Hong Kong and to investigate the predictive abilities of a set of selected variables on the outcomes. At 1-month recovery, 100 SARS survivors (mean age = 37; 66 women) and 184 community subjects completed self-administered questionnaires. In the General Health Questionnaire-28, 61% of the SARS survivors were identified as distressed cases under a conservative cutoff score of 6. Compared with the community sample, SARS survivors had significantly more distress and poor quality of life. Being a healthcare worker, severity of SARS symptoms, steroid dosage, and social support accounted for a portion of variances of different measures. Early psychiatric screening and intervention may be beneficial for the adjustment of SARS survivors after short-term recovery. Future research on the long-term impact of SARS is recommended.

Background and Objectives: There are limited data on the night-to-night variability of childhood sleep-related disordered breathing (SDB). We aim to assess for the presence of first-night effect (FNE) and to examine whether a single-night sleep study is adequate in the assessment of childhood SDB., Design: In a case-control study investigating whether obesity is a risk factor for childhood SDB, the night-to-night variability of sleep and respiratory variables were studied., Participants and Setting: Forty-six obese children from a pediatric obesity clinic and 44 age- and sex-matched normal weight control subjects from local schools., Interventions: All subjects underwent two consecutive overnight polysomnographic studies. An obstructive apnea index (OAI) >/= 1/h was considered diagnostic of SDB., Results: The mean age of the children was 11.21 years (SD 2.21). Forty-four obese children and 43 control subjects completed the 2-night study. Based on the criterion of the worst OAI over the 2 nights, 13 subjects were found to have SDB, 12 subjects were primary snorers, and 62 were normal subjects. In all subjects, the sleep efficiency improved and sleep-onset latency was reduced on the second night. While there was a rebound of rapid eye movement sleep with the associated worsening of respiratory indexes (mainly accounted for by an increase in central apneas and hypopneas) evident in normal subjects, there was a significant improvement of respiratory disturbances in the SDB group on the second night. The first-night polysomnography would have correctly identified 84.6% of cases as defined by the criteria of the worst OAI over the 2 nights. All cases missed by the first-night study had only borderline OAI., Conclusions: The phenomenon of FNE in children was well demonstrated in our study. We proposed that a single-night sleep study is adequate and more cost-effective in assessing for childhood SDB.

In denitrification, nir and nor genes are respectively required for the sequential dissimilatory reduction of nitrite and nitric oxide to form nitrous oxide. Their location on the pSymA megaplasmid of Sinorhizobium meliloti was confirmed by Southern hybridization of its clones with specific structural gene probes for nirK and norCB. A 20-kb region of pSymA containing the nor-nir genes was delineated by nucleotide sequence analysis. These genes were linked to the nap genes encoding periplasmic proteins involved in nitrate reduction. The nor-nir-nap segment is situated within 30 kb downstream from the nos genes encoding nitrous oxide reduction, with a fix cluster intervening between nir and nos. Most of these predicted nor-nir and accessory gene products are highly homologous with those of related proteobacterial denitrifiers. Functional tests of Tn5 mutants confirmed the requirement of the nirV product and 1 unidentified protein for nitrite reduction as well as the norB-D products and another unidentified protein for nitric oxide reduction. Overall comparative analysis of the derived amino acid sequences of the S. meliloti gene products suggested a close relationship between this symbiotic N2 fixer and the free-living non-N2-fixing denitrifier Pseudomonas G-179, despite differences in their genetic organization. This relationship may be due to lateral gene transfer of denitrification genes from a common donor followed by rearrangement and recombination of these genes.

In February 2003, Hong Kong was hit by a community-wide outbreak of severe acute respiratory syndrome (SARS). During the period of the outbreak, 10 patients with SARS with psychiatric complications were referred to our Consultation and Liaison Psychiatry Team for assessment and management. We found that both the direct and indirect effects of SARS such as symptom severity, total isolation during treatment and administration of steroid were probable causes of psychiatric complications. In this paper, we report on the nature of their psychiatric problems, challenges to management and psychiatric treatment strategies used during the acute phase.

Bacteria were isolated from a cultivated soil and screened for antagonistic activity against Fusarium graminearum, a predominant agent of ear rot and head blight in cereal crops. Based on its in vitro effectiveness, isolate D1/2 was selected for characterization and identified as a strain of Bacillus subtilis by phenotypic tests and comparative analysis of its 16S ribosomal RNA gene (rDNA) sequence. It inhibited the mycelial growth of a collection of common fungal phytopathogens, including eight Fusarium species, three other ascomycetes, and one basidiomycete. The cell-free culture filtrate of D1/2 at different dilutions was active against macroconidium germination and hyphal growth of F. graminearum, depending on the initial macroconidium density. It induced the formation of swollen hyphal cells in liquid cultures of this fungus grown from macroconidia. A bioassay also demonstrated that D1/2 offered in planta protection against the damping-off disease in alfalfa seedlings caused by F. graminearum, while the type strain of B. subtilis was ineffective. Hence, B. subtilis D1/2 or its culture filtrate has potential application in controlling plant diseases caused by Fusarium.

Background: Limited data exist in the literature concerning the characteristics of erythema following psoralen UV-A (PUVA) treatment using topical methoxsalen. To optimize the phototherapeutic regimen and reduce short- and long-term risks, knowledge of such basic information is essential., Observations: The characteristics of PUVA erythema following 15- and 5-minute immersion in methoxsalen was determined. The PUVA erythema after 15-minute methoxsalen immersion exhibited a broad peak, with the lowest median minimal phototoxic dose (MPD) at 96, 120, and 144 hours after UV-A irradiation. Seventy-three percent of subjects experienced peak erythema at 120 hours compared with only 45% at 72 hours. From the dose-response data, an increase in the erythema index of 0.025 (equivalent to the MPD) was significantly lower when determined at 120 hours after UV-A irradiation than at 72 hours (P =.03). The median maximum slope of the dose-response curve occurred at 144 hours. After 5-minute immersion, PUVA erythema displayed a broad peak from 72 hours. Erythema summation scores followed a trend similar to that of 15-minute immersion, but the intensity was significantly reduced., Conclusions: Methoxsalen-UV-A erythema exhibited a broad plateau between 96 and 144 hours, with most subjects at peak erythema at 120 hours. Reduction of methoxsalen immersion time significantly lowered the erythemal intensity. Minimum phototoxic dose reading at 72 hours underestimates the phototoxic effect of topical methoxsalen PUVA, and a change in the MPD assessment time should be considered.

Narcolepsy is a lifelong, crippling sleep disorder. Although the discovery of the hypocretin system has been a breakthough in genetics, the epidemiological aspects of narcolepsy remain elusive. Ethnic predisposition was suggested to partially account for the 2,500-fold difference in the reported prevalence rates of narcolepsy between Japanese (0.59%) and Israeli Jews (0.00023%). We carried out a general population study, conducting a random telephone survey with a structured questionnaire, which included a validated screening instrument (a Chinese version of the Ullanlinna Narcolepsy Scale). It was followed by clinical-polysomnographic-HLA confirmation of the subjects determined to be positive for narcolepsy based on the questionnaire. Of 9,851 subjects interviewed, 28 subjects (0.28%, 58% female) were screened positive. Ninety percent had a second detailed interview, 64% had HLA typing, and over half of them had a sleep assessment. Only three subjects were found to have genuine narcolepsy. The most common nonnarcolepsy diagnoses were sleep apnea syndrome and sleep-wake schedule disorder. The prevalence rate of narcolepsy in Southern (Hong Kong) Chinese was found to be 0.034% (95% confidence interval = 0.010-0.117%). All available narcoleptic subjects were HLA DRB1-1501 positive and 50% were DQB1-0602 positive. The prevalence rate of narcolepsy among Chinese is comparable to the rates for other populations in studies with stringent epidemiological designs, suggesting that major cross-ethnic differences in the prevalence rates of narcolepsy previously reported likely resulted from methodological limitations.

A 10-year retrospective analysis of the use of psoralen photochemotherapy (PUVA) in the treatment of vitiligo was undertaken at the St John's Institute of Dermatology, London, UK. Of 97 patients included in this study, eight had complete or almost complete repigmentation, 59 moderate to extensive repigmentation, and 30 showed little or no response. However, 24 of those who had responded to PUVA with extensive repigmentation did not consider their response satisfactory because of persistence of vitiligo at cosmetically sensitive sites, and poorly matching, speckled repigmentation. Fifty-seven patients who initially improved with PUVA therapy subsequently relapsed, in most cases within a year of stopping treatment. Relapses in 22 patients were on the same cutaneous sites as previously affected, while vitiligo at new sites developed in 20 patients and both new and old sites were affected in a further 15 patients. Patients who retained their pigmentation after 2 years appeared to have a better chance of permanent remission. The only statistically significant prognostic indicator of relapse was patient age at the start of treatment, younger patients tending to retain their pigmentation longer than older patients. This study emphasizes the need for careful patient counselling before PUVA therapy as this treatment seldom achieves extensive repigmentation that is cosmetically acceptable, and treatment response is often followed by relapse.

Background: Photochemotherapy (PUVA) is beneficial for the treatment of various dermatoses. The introduction of ultraviolet B and narrow-band ultraviolet B phototherapy has had a significant impact on the role of PUVA in dermatology. This study aims to assess the current role of PUVA in treating dermatoses, in a predominantly Asian population, at the National Skin Centre in Singapore., Materials and Methods: We reviewed the clinical data of 115 patients who were started on PUVA treatment at the National Skin Centre, Singapore in 1998. We analysed the epidemiology data, the clinical response rate and the adverse effects of PUVA therapy. All of the patients continued to have ongoing maintenance treatment., Results: Most of our patients were Chinese (74.8%) and male (58.3%), ranging from the ages of 4 to 74 years. Vitiligo (60.9%) was the commonest skin disorder treated with PUVA, followed by psoriasis (20.9%), endogenous eczema (11.3%), mycosis fungoides (3.5%), lichen amyloidosis (2.6%) and prurigo nodularis (0.9%). Most of our patients received paint PUVA (50.4%), 33.9% oral PUVA and 15.7% bath PUVA. The best clinical response--those patients achieving a greater that 50% clearance--was observed in patients with endogenous eczema, psoriasis and mycosis fungoides (76.8%, 73.9% and 60%, respectively). Of the vitiliginous patients, 54.3% experienced a poor response to PUVA therapy. The main side effects were mild erythema and pruritus., Conclusion: PUVA remains a valuable, well-tolerated therapeutic option for a variety of dermatoses.

The understanding of human hemoglobin ontogeny during development is of biological and clinical importance. Molecular and immunocytological techniques were used to study the expression of embryonic zeta (zeta), epsilon (epsilon), and fetal gamma (gamma) globin genes in newborn cord blood, peripheral blood from men, pregnant and non-pregnant women, and in vitro mononuclear cell cultures. We have shown that embryonic and fetal globin mRNA and peptides are expressed in cultured erythroid cells and in circulating blood cells from newborns, adult non-pregnant women and from men. The findings suggest that during erythroid cell differentiation in newborns and adults, there is a transient recapitulation of sequential globin chain expression as found during embryonic and fetal development. Furthermore, these findings underscore the need for caution in using embryonic and fetal globin chains as markers to identify erythroid cells of fetal origin in maternal circulation for prenatal diagnosis., (Copyright 2001 John Wiley & Sons, Ltd.)

Introduction: A retrospective study of melanocytic naevi was undertaken to assess the degree of clinico-pathological correlation and incidence of histological atypia., Materials and Methods: The case records from January to March 1996 of all patients with histologically diagnosed melanocytic naevi at the National Skin Centre were analysed., Results: Of the 240 lesions removed from 167 patients, the majority being women (111/167 patients), it was found that 55% (132/240) were correctly diagnosed. Fourteen per cent were mistaken for non-melanocytic lesions, namely skin tag, neurofibroma, syringoma cylindroma, epidermal naevus, naevus sebaceous and basal cell carcinoma. Most of the lesions were located on the cheeks and eyelids. Junctional naevi, followed by compound naevi were often missed. Histological dysplasia were seen in 7 naevi; 6 compound and 1 congenital naevi. There was a lack of clinico-pathological concordance in dysplastic naevi., Conclusions: The clinico-pathological concordance of melanocytic naevi was high, with low incidence of atypia on histology.

Background: Candidal infections of the skin/nails and vagina are very common worldwide. Various in vitro test systems are available to help to determine the antifungal activity of drugs. The minimum inhibitory concentration (MIC) is a standard measure of the in vitro potency of drugs against yeasts., Methods: Vaginal smears and skin/nail scrapings of 50 consecutive patients with candidal vaginitis and 46 consecutive patients (28 women, 18 men) with cutaneous/nail candidosis were used in the study. Direct microscopy and culture from vaginal smears and skin scrapings were performed on all patients. The MICs were determined using the broth dilution method., Results: For vaginal candidosis, the mean age of the patients was 28.2 years (range, 9-49 years). Candida albicans accounted for 58% of the isolates, C. glabrata for 32%, C. tropicalis for 6%, and C. parasilosis for 4%. At the MIC of < or = 4 mg/L, 65-95% of C. albicans, 66-94% of C. glabrata, 33-100% of C. tropicalis, and 0-50% of C. parasilosis were susceptible to the drugs tested (ketoconazole, itraconazole, nystatin, amorolfine, clotrimazole, and miconazole). For cutaneous/nail candidosis, the mean age of the patients was 45 years (range, 19-82 years). C. albicans made up 59% of the isolates, C. parasilosis 20%, C. krusei 13%, C. glabrata 4%, and C. tropicalis 4%. At the MIC of < or = 4 mg/L, 59-96% of C. albicans, 100% of C. glabrata, 83-100% of C. krusei, 89-100% of C. parasilosis, and 100% of C. tropicalis were susceptible to the drugs tested (ketoconazole, itraconazole, nystatin, amorolfine, clotrimazole, and miconazole)., Conclusions: C. albicans is the most common Candida species causing cutaneous/nail and vaginal candidosis in Singapore. The in vitro antifungal activities of ketoconazole, itraconazole, nystatin, amorolfine, clotrimazole, and miconazole are similar against the various Candida species. C. parasilosis in vaginal candidosis appears to be less susceptible. Here, itraconazole and amorolfine may be more effective.