Hierarchical measurement structure in the Women's Health Questionnaire: a confirmatory factor analysis.

Purpose: This study conducted confirmatory factor analysis (CFA) to examine the measurement structure of the Women's Health Questionnaire (WHQ) and how its components were organized. Methods: Participants were 448 postmenopausal women, with a mean age of 63.3 years. CFA was conducted to test how well several proposed measurement models fit the data. Results: The single-factor model performed poorly, indicating the presence of multiple factors. The model with seven correlated factors fit the data well, although the varying degrees of inter-factor correlations suggested grouping of similar factors. The hierarchical measurement structure, with seven first-order factors organized under two second-order factors of physical health and mental health functioning, demonstrated a good fit with the data (χ2(367) = 694.05, p < 0.001; root mean square error of approximation = 0.05; comparative fit index = 0.95) and a meaningful pattern. The Mental Health factor was represented by Depressed Mood, Anxiety/Fear, Memory/Concentration Problems, and Sleep Problems. The Physical Health factor was manifested mainly by Somatic Symptoms, Menstrual Symptoms, and Vasomotor Symptoms, and, to a lesser extent, also by Sleep Problems and Memory/Concentration Problems. Conclusion: Findings suggested that, in addition to a global index and subscale scores, the WHQ may produce summary scores of physical health and mental health functioning in evaluation of well-being among postmenopausal women.

Paediatric case series of drug reaction with eosinophilia and systemic symptoms (DRESS): 12-year experience at a single referral centre in Hong Kong and the first reported use of infliximab.

Summary: DRESS (drug reaction with eosinophilia and systemic symptoms) is a rare but potentially life-threatening disorder characterized by fever, skin eruption, haematological abnormalities and multi-organ dysfunction after drug exposure. The pathophysiology is thought to be related to interactions between culprit drugs, viral reactivation and T-lymphocytes activation. We report 4 paediatric patients with DRESS who were treated at our centre over the past 12 years. Most cases improved after corticosteroids. Other immunosuppressive medications were attempted in refractory cases with varied outcomes. Patient 3 was the first reported case that involved the use of infliximab, a TNF-α inhibitor, for DRESS. Although clinical efficacy was not observed for this one patient, a previous study demonstrated that patients with DRESS, disease progression and HHV-6 reactivation had elevated pre-treatment TNF- α and IL-6 levels. Further research is needed to explore the role of these cytokines in DRESS.

The effects of global warming on allergic diseases.

Global warming is a public health emergency. Substantial scientific evidence indicates an unequivocal rising trend in global surface temperature that has caused higher atmospheric levels of moisture retention leading to more frequent extreme weather conditions, shrinking ice volume, and gradually rising sea levels. The concomitant rise in the prevalence of allergic diseases is closely related to these environmental changes because warm and moist environments favour the proliferation of common allergens such as pollens, dust mites, molds, and fungi. Global warming also stresses ecosystems, further accelerating critical biodiversity loss. Excessive carbon dioxide, together with the warming of seawater, promotes ocean acidification and oxygen depletion. This results in a progressive decline of phytoplankton and fish growth that in turn promotes the formation of larger oceanic dead zones, disrupting the food chain and biodiversity. Poor environmental biodiversity and a reduction in the microbiome spectrum are risk factors for allergic diseases in human populations. While climate change and the existence of an allergy epidemic are closely linked according to robust international research, efforts to mitigate these have encountered strong resistance because of vested economic and political concerns in different countries. International collaboration to establish legally binding regulations should be mandatory for forest protection and energy saving. Lifestyle and behavioural changes should also be advocated at the individual level by focusing on low carbon living; avoiding food wastage; and implementing the 4Rs: reduce, reuse, recycle, and replace principles. These lifestyle measures are entirely consistent with the current recommendations for allergy prevention. Efforts to mitigate climate change, preserve biodiversity, and prevent chronic diseases are interdependent disciplines.

Effects of testosterone administration on cognitive function in hysterectomized women with low testosterone levels: a dose-response randomized trial.

PURPOSE: To determine the dose-dependent effects of testosterone administration on cognition in women with low testosterone levels. METHODS: 71 hysterectomized women with or without oophorectomy with total testosterone <31 ng/dl and/or free testosterone <3.5 pg/ml received a standardized transdermal estradiol regimen during the 12-week run-in period and were then randomized to receive weekly intramuscular injections of placebo, 3, 6.25, 12.5, or 25 mg testosterone enanthate for 24 weeks. Total testosterone was measured in serum by LC-MS/MS, and free testosterone levels were measured by equilibrium dialysis. Cognitive function was evaluated using a comprehensive battery of standardized neuropsychological tests at baseline and 24 weeks. RESULTS: 46 women who had baseline and end-of-treatment cognitive function data constituted the analytic sample. The five groups were similar at baseline. Mean on-treatment nadir total testosterone concentrations were 15, 89, 98, 134, and 234 ng/dl in the placebo, 3, 6.25, 12.5, and 25 mg groups, respectively. No significant changes in spatial ability, verbal fluency, verbal memory, or executive function were observed in any treatment arm compared to placebo even after adjustment for baseline cognitive function, age, and education. Multiple regression analysis did not show any significant relation between changes in testosterone concentrations and change in cognitive function scores. CONCLUSION: Short-term testosterone administration over a wide range of doses for 24 weeks in women with low testosterone levels was neither associated with improvements nor worsening of cognitive function.

Exome sequencing identifies novel compound heterozygous mutations of IL-10 receptor 1 in neonatal-onset Crohn's disease.

Inflammatory bowel disease is well recognized for a strong genetic involvement in its pathogenesis. Homozygous mutations in interleukin-10 receptor 1 (IL-10R1) identified by linkage analysis were shown to be involved in this disorder. However, the underlying molecular mechanism and the causal nature of the mutations in the disease process remain to be clarified. In this study, using whole exome sequencing, we identified novel compound heterozygous missense mutations in the extracellular domain of IL-10R1 in a Crohn's disease patient from a non-consanguineous family. These mutations did not affect IL-10R1 expression, nor IL-10 binding. However, they abrogated IL-10R1 phosphorylation induced by IL-10, therefore leading to impaired STAT3 activation and suppression of inflammatory responses. After reconstitution with wild-type IL-10R1, the patient cells showed fully restored IL-10R function including IL-10-induced STAT3 activation and expression of suppressor of cytokine signaling 3. Thus, our results demonstrated that the mutations in IL-10R1 extracellular domain impair IL-10R1 activation rather than IL-10 binding, indicating these residues are important in IL-10 signal transduction through IL-10R1. The reconstitution data also confirmed the causality of the IL-10R1 mutations.

Association of CD247 with systemic lupus erythematosus in Asian populations.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance. CD247 (CD3Z, TCRZ) plays a vital role in antigen recognition and signal transduction in antigen-specific immune responses, and is known to be involved in SLE pathogenesis. Weak disease association was reported for genetic variants in this gene in Caucasian studies for SLE, Crohn's disease and systemic sclerosis, but its role as a genetic risk factor was never firmly established. METHODS: In this study, using a collection of 612 SLE patients and 2193 controls of Chinese ethnicity living in Hong Kong in a genome-wide study, single nucleotide polymorphisms (SNPs) in and around CD247 were identified as being associated with SLE. The two most significant SNPs in this locus were selected for further replication using TaqMan genotyping assay in 3339 Asian patients from Hong Kong, Mainland China, and Thailand, as well as 4737 ethnically and geographically matched controls. RESULTS: The association of CD247 with SLE in Asian populations was confirmed (rs704853: odds ratio [OR] = 0. 81, p = 2.47 × 10(-7); rs858543: OR = 1.10, p = 0.0048). Patient-only analysis suggested that rs704853 is also linked to oral ulcers, hematologic disorders and anti-double-stranded DNA (dsDNA) antibody production. CONCLUSION: A significant association between variants in CD247 and SLE was demonstrated in Asian populations. Understanding the involvement of CD247 in SLE may shed new light on disease mechanisms and development of new treatment paradigms.

Two missense variants in UHRF1BP1 are independently associated with systemic lupus erythematosus in Hong Kong Chinese.

UHRF1BP1 encodes a highly conserved protein with unknown function. Previously, a coding variant in this gene was found to be associated with systemic lupus erythematosus (SLE) in populations of European ancestry (rs11755393, R454Q, P=2.22 x 10⁻8, odds ratio=1.17). In this study, by a combination of genome-wide study and replication involving a total of 1230 patients and 3144 controls, we confirmed the association of this coding variant to SLE in Hong Kong Chinese. We also identified another coding variant in this gene that independently contributes to SLE susceptibility (rs13205210, M1098T, P=4.44 x 10⁻9, odds ratio=1.49). Cross-population confirmation establishes the involvement of this locus in SLE and indicates that distinct alleles are contributing to disease susceptibility.

Analgesic and sedative effects of intranasal dexmedetomidine in third molar surgery under local anaesthesia.

BACKGROUND: Dexmedetomidine (DEX) is an alpha 2-adrenoreceptor agonist, which induces sedation and analgesia. This study aimed to determine whether intranasal DEX offered perioperative sedation and better postoperative analgesia. METHODS: Patients having unilateral third molar surgery under local anaesthesia were recruited and allocated to receive either intranasal DEX 1 µg kg(-1) (Group D) or same volume of saline (Group P) 45 min before surgery. Patient-controlled sedation with propofol was offered as a rescue sedative. Perioperative sedation, postoperative pain relief and analgesic consumption, vital signs, adverse events, postoperative recovery, and satisfaction in sedation and analgesia were assessed. RESULTS: Thirty patients from each group were studied. Areas under curve (AUC) of postoperative numerical rating scale (NRS) pain scores 1-12 h at rest and during mouth opening were significantly lower in Group D (P=0.003 and 0.009, respectively). AUC BIS values and OAA/S sedation scores were significantly lower before surgery and at the recovery area (all P<0.01) with significantly less intra-operative propofol used in group D (P<0.01). In group D, heart rate was significantly lower at recovery period (P=0.005) while systolic blood pressure in different periods of the study (all P<0.01), but the decreases did not require treatment. More patients from placebo group experienced dizziness (P=0.026) but no serious adverse event was found. No difference was found in postoperative psychomotor recovery and satisfaction in pain relief and sedation. CONCLUSIONS: Patients receiving intranasal DEX for unilateral third molar surgery with local anaesthesia were more sedated perioperatively with better postoperative pain relief. No delay in psychomotor recovery was seen.

Population differences in SLE susceptibility genes: STAT4 and BLK, but not PXK, are associated with systemic lupus erythematosus in Hong Kong Chinese.

In this study, we compared the association of several newly discovered susceptibility genes for systemic lupus erythematosus (SLE) between populations of European origin and two Asian populations. Using 910 SLE patients and 1440 healthy controls from Chinese living in Hong Kong, and 278 SLE patients and 383 controls in Thailand, we studied association of STAT4, BLK and PXK with the disease. Our data confirmed association of STAT4 (rs7574865, odds ratio (OR) =1.71, P=3.55 x 10(-23)) and BLK (rs13277113, OR=0.77, P=1.34 x 10(-5)) with SLE. It was showed that rs7574865 of STAT4 is also linked to hematologic disorders and potentially some other subphenotypes of the disease. More than one genetic variant in STAT4 were found to be associated with the disease independently in our populations (rs7601754, OR=0.59, P=1.39 x 10(-9), and P=0.00034 when controlling the effect of rs7574865). With the same set of samples, however, our study did not detect any significant disease association for PXK, a risk factor for populations of European origin (rs6445975, joint P=0.36, OR=1.06, 95% confidence interval: 0.93-1.21). Our study indicates that some of the susceptibility genes for this disease may be population specific.

Association of BANK1 and TNFSF4 with systemic lupus erythematosus in Hong Kong Chinese.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance. Recently, single nucleotide polymorphisms (SNPs) in BANK1 and TNFSF4 have been shown to be associated with SLE in Caucasian populations, but it is not known whether they are also involved in the disease in other ethnic groups. Recent data from our genome-wide association study (GWAS) for 314 SLE cases and 920 controls collected in Hong Kong identified SNPs in and around BANK1 and TNFSF4 to be associated with SLE risk. On the basis of the results of the reported studies and our GWAS, SNPs were selected for further genotyping in 949 SLE patients (overlapping with the 314 cases in our GWAS) and non-overlapping 1042 healthy controls. We confirmed the associations of BANK1 and TNFSF4 with SLE in Chinese (BANK1, rs3733197, odds ratio (OR)=0.84, P=0.021; BANK1, rs17266594, OR=0.61, P=4.67 x 10(-9); TNFSF4, rs844648, OR=1.22, P=2.47 x 10(-3); TNFSF4, rs2205960, OR=1.30, P=2.41 x 10(-4)). Another SNP located in intron 1 of BANK1, rs4522865, was separately replicated by Sequenom in 360 cases and 360 controls and was also confirmed to be associated with SLE (OR=0.725, P=2.93 x 10(-3)). Logistic regression analysis showed that rs3733197 (A383T in ankyrin domain) and rs17266594 (a branch point-site SNP) from BANK1 had independent contributions towards the disease association (P=0.037 and 6.63 x 10(-8), respectively). In TNFSF4, rs2205960 was associated with SLE independently from the effect of rs844648 (P=6.26 x 10(-3)), but not vice versa (P=0.55). These findings suggest that multiple independent genetic variants may be present within the gene locus, which exert their effects on SLE pathogenesis through different mechanisms.

Daily rhythm in human urinary melatonin.

The melatonin in urine samples from six healthy adult volunteers was concentrated on Amberlite XAD-2 resin, eluted with organic solvents, and quantitated by use of a bioassay technique (the dermal melanaphore response of larval anurans to melatonin in their bathing medium). The melatonin content of samples collected between 11 p.m. and 7 a.m. was, in each case, several times higher than that of samples collected between 7 a.m. and 3 p.m. or between 3 p.m. and 11 p.m.

Genome-wide expression monitoring in Saccharomyces cerevisiae.

The genomic sequence of the budding yeast Saccharomyces cerevisiae has been used to design and synthesize high-density oligonucleotide arrays for monitoring the expression levels of nearly all yeast genes. This direct and highly parallel approach involves the hybridization of total mRNA populations to a set of four arrays that contain a total of more than 260,000 specifically chosen oligonucleotides synthesized in situ using light-directed combinatorial chemistry. The measurements are quantitative, sensitive, specific, and reproducible. Expression levels ranging from less than 0.1 copies to several hundred copies per cell have been measured for cells grown in rich and minimal media. Nearly 90% of all yeast mRNAs are observed to be present under both conditions, with approximately 50% present at levels between 0.1 and 1 copy per cell. Many of the genes observed to be differentially expressed under these conditions are expected, but large differences are also observed for many previously uncharacterized genes.

Cutaneous tuberculosis in Hong Kong: an update.

OBJECTIVE: To provide an update on cutaneous tuberculosis in Hong Kong. DESIGN: Retrospective study. SETTING: Social Hygiene Service (Dermatology Division), the largest dermatological referral centre in Hong Kong. PATIENTS: Patients presented with cutaneous tuberculosis between 1993 and 2002 inclusive. Case notes, histology reports, and microbiological reports were reviewed with particular reference to the epidemiology, duration of illness, history of contact with tuberculosis, culture results, and response to treatment. RESULTS: There were 147 patients with cutaneous tuberculosis; among these a few had true cutaneous tuberculosis (n = 16) and the remainder were tuberculids (n = 131). In all they accounted for 0.04% of new dermatology cases diagnosed. Cases of cutaneous tuberculosis were distributed as follows: lupus vulgaris (n = 6, 4%), tuberculosis verrucosa cutis (n = 6, 4%), tuberculosis of the skin unclassified (n = 2, 1%), and orificial tuberculosis (n = 2, 1%). Culture and polymerase chain reaction was positive in less than half of the latter cases. All responded well to anti-tuberculosis therapy. Erythema induratum was the most common form (n = 127, 86%), but papulonecrotic tuberculids (n = 4, 3%) were uncommon. Erythema induratum affected the lower limb in all patients, with a female predominance, and responded to isoniazid monotherapy, multidrug anti-tuberculosis therapy, or doxycycline. CONCLUSION: Lupus vulgaris and tuberculosis verrucosa cutis remain the commonest forms of true cutaneous tuberculosis, and erythema induratum is the most common tuberculid. Culture and polymerase chain reaction are positive in a small proportion of patients.

Atypical mycobacterial cutaneous infections in Hong Kong: 10-year retrospective study.

OBJECTIVE: To review the epidemiology of atypical mycobacterial cutaneous infection in Hong Kong. DESIGN: Retrospective study. SETTING: Social Hygiene Service (Dermatology Division), the largest dermatological referral centre in Hong Kong. PATIENTS: Patients with a diagnosis of atypical mycobacterial cutaneous infection based on clinical features, histopathology, with or without a positive culture during the period 1993 to 2002. MAIN OUTCOME MEASURES: Epidemiological data, clinical features, histology, microbiological investigation, and treatment response. RESULTS: Of 345,394 dermatological cases presented over the 10-year period, 33 (0.0096%) cases (19 male, 14 female) of atypical mycobacterial cutaneous infection were diagnosed. The most common type of infection was caused by Mycobacterium marinum (n=17, 51.5%), followed by Mycobacterium avium-intracellulare (n=3, 9.1%) and Mycobacterium chelonae (n=2, 6.1%). The upper limb, especially the hands and fingers, was the most common (69.7%) site of involvement. Tissue culture was positive in 18 (54.5%) cases. All biopsies showed granulomatous histology. Thirty-two patients received treatment and 31 responded. Twenty-six were treated with oral tetracycline group of antibiotics (minocycline, doxycycline, tetracycline). The duration of treatment ranged from 8 to 54 weeks (mean, 24 weeks). Mild transient adverse effects to treatment were reported in six cases. CONCLUSION: Atypical mycobacterial infection is rare in Hong Kong. Because of the low sensitivity of traditional culture techniques, atypical mycobacterial infection may be underdiagnosed if only culture-confirmed cases are included. Polymerase chain reaction provides a rapid and sensitive method to improve diagnostic accuracy. Tissue culture is crucial to determine antimicrobial susceptibility. In our study, tetracycline group of antibiotics, especially minocycline, was an effective treatment, particularly in cases caused by Mycobacterium marinum.

Kawasaki disease in Hong Kong, 1994 to 2000.

OBJECTIVE: To describe the epidemiology, clinical characteristics, and management of Kawasaki disease in children in Hong Kong. DESIGN: Retrospective survey of medical records from July 1994 to June 1997, and prospective data collection from July 1997 to June 2000. SETTING: Hospitals with a paediatric unit in Hong Kong. PATIENTS: Patients diagnosed with Kawasaki disease between July 1994 and June 2000 in public hospitals in Hong Kong. MAIN OUTCOME MEASURES: Incidence of Kawasaki disease and coronary artery aneurysm rates. RESULTS: A total of 696 cases of Kawasaki disease were reported. There were 435 (62.5%) boys and 261 (37.5%) girls giving a male to female ratio of 1.7:1. The age ranged from 1 month to 15 years 5 months with a median of 1.7 years. Infants (<1 year) constituted the largest group of patients (223, 32.0%) and overall, 638 (91.7%) were younger than 5 years. Skin rash, conjunctivitis, and oral signs were among the principal clinical features present in over 80% of cases. Prominent cervical lymph nodes larger than 1.5 cm were less commonly found (24%). Coronary artery aneurysms or ectasia were present in 15.7% (109/696), 8.5% (59/696), and 5.0% (35/696) of patients at 2, 4, and 8 weeks, respectively. The incidence of Kawasaki disease per 100,000 children under 5 years was significantly higher in the prospective study period than in the retrospective period (39 vs 26, P<0.001). CONCLUSION: The incidence of Kawasaki disease is high in Hong Kong and is 39 per 100,000 children below 5 years of age. The coronary artery aneurysm prevalence is 5%. Intravenous gamma-globulin and high-dose aspirin is the mainstay of treatment.

Validity domain of the weak-phase-object approximation for electron diffraction of thin protein crystals.

The domain of validity of the weak-phase-object (WPO) approximation is evaluated for high-energy electrons (100 keV, 500 keV and 1 MeV) scattered by crystalline biological macromolecules. Cytochrome b5 is used as an example in which calculated dynamical diffraction intensities are used to simulate observed diffraction intensities which are then compared with intensities calculated by the weak-phase-object approximation. Three criteria of validity are used, namely the crystallographic residual (R value), the interpretability of difference Patterson maps, and the results of phasing by the heavy-atom isomorphous replacement method. The present calculations indicate that the error associated with the WPO approximation is quite acceptable up to a specimen thickness of 200 A for 100 keV electrons, which is two to four times the thickness limit for crystalline organic structures with much smaller unit-cell dimensions. An equally acceptable thickness limit at 500 keV and 1MeV is about 300-350 A.

HIV-associated eosinophilic folliculitis in a Chinese woman: a case report and a survey in Hong Kong.

This is the first survey of eosinophilic folliculitis (EF) in patients infected with the human immunodeficiency virus (HIV) in Hong Kong. The present report provides the local data on HIV-associated eosinophilic folliculitis (HIV-EF) and includes the first Chinese, heterosexual female patient with this condition. This is a retrospective study on all HIV-positive patients (n = 451) attending the outpatient clinic of the AIDS Unit in Hong Kong. Patients diagnosed as having EF with histological support were included for analysis. The data were presented by descriptive method. Three patients were identified, all of them had skin biopsies done which confirmed the diagnosis; including the female case. Recognition of HIV-EF is important because it is indicative of significant immunosuppression with risk of opportunistic infection. We concluded that HIV-EF is no longer an exclusive male disease in homosexual patients only. We expect more female patients or heterosexual subjects who are HIV positive developing this disease in the future.

PIP: A retrospective record review of HIV-associated eosinophilic pustular folliculitis (EF) cases in 451 HIV-positive patients attending an outpatient AIDS clinic in Hong Kong revealed the first female case of HIV-EF in a Chinese heterosexual woman. A 45-year-old HIV-positive woman presented with a 2-week history of pruritic papulopustular eruption on the face. Clinical examination revealed multiple erythematous follicular papules and pustules on her face and neck. Histologic examination of a skin biopsy indicated spongiosis and exocytosis in the epidermis involving infundibulum and sebaceous glands with micropustule formation. This patient's EF responded well to treatment with ultraviolet B phototherapy. This record review also revealed 2 HIV-EF cases in Chinese men (1 homosexual and 1 heterosexual). In previous series, HIV-EF has been found only in homosexual men.

Poikiloderma-like cutaneous amyloidosis in an ethnic Chinese girl.

Primary cutaneous amyloidosis is the deposition of amyloid in the skin without involvement of internal organs. It is easily diagnosed when presented in its typical manifestation. Atypical or rare clinical presentations can pose diagnostic difficulties. Poikiloderma-like cutaneous amyloidosis (PCA), a rare variant of primary cutaneous amyloidosis, was first reported in the literature in 1936 (1). It is characterised by: 1) poikilodermatous skin lesions; 2) lichenoid papules; 3) cutaneous amyloid deposit in the pigmented and lichenoid lesions; 4) light sensitivity; 5) short stature; and 6) other features such as blister formation or palmoplantar keratosis. Ogino coined the term PCA syndrome when these unusual features present early in life (2). We report a 26-year-old Chinese woman who presented with poikilodermatous skin lesions and was misdiagnosed as poikiloderma atrophica vasculare (PAV) on the basis of clinical appearance without any histological proof. The diagnosis of PCA was made after skin biopsy which showed amyloid deposits in the skin. This condition can easily be confused with other true poikiloderma skin diseases. Histology is important in confirming the diagnosis.