Aetiological bases of 46,XY disorders of sex development in the Hong Kong Chinese population.

OBJECTIVE: Disorders of sex development are due to congenital defects in chromosomal, gonadal, or anatomical sex development. The objective of this study was to determine the aetiology of this group of disorders in the Hong Kong Chinese population. SETTING: Five public hospitals in Hong Kong. PATIENTS: Patients with 46,XY disorders of sex development under the care of paediatric endocrinologists between July 2009 and June 2011. MAIN OUTCOME MEASURES: Measurement of serum gonadotropins, adrenal and testicular hormones, and urinary steroid profiling. Mutational analysis of genes involved in sexual differentiation by direct DNA sequencing and multiplex ligation-dependent probe amplification. RESULTS: Overall, 64 patients were recruited for the study. Their age at presentation ranged from birth to 17 years. The majority presented with ambiguous external genitalia including micropenis and severe hypospadias. A few presented with delayed puberty and primary amenorrhea. Baseline and post-human chorionic gonadotropin-stimulated testosterone and dihydrotestosterone levels were not discriminatory in patients with or without AR gene mutations. Of the patients, 22 had a confirmed genetic disease, with 11 having 5α-reductase 2 deficiency, seven with androgen insensitivity syndrome, one each with cholesterol side-chain cleavage enzyme deficiency, Frasier syndrome, NR5A1-related sex reversal, and persistent Müllerian duct syndrome. CONCLUSIONS: Our findings suggest that 5α-reductase 2 deficiency and androgen insensitivity syndrome are possibly the two most common causes of 46,XY disorders of sex development in the Hong Kong Chinese population. Since hormonal findings can be unreliable, mutational analysis of the SRD5A2 and AR genes should be considered the first-line tests for these patients.

Social obstetrics: non-local expectant mothers admitted through accident and emergency department in a public hospital in Hong Kong.

OBJECTIVES: To review the pregnancy outcomes of non-booked, non-local pregnant women delivering in Kwong Wah Hospital via admission to the Accident and Emergency Department 1 year after the announcement by the Hospital Authority to stop antenatal booking for non-eligible persons; and to perform a literature review of local studies about non-eligible person deliveries over the last decade. DESIGN: Case series. SETTING: A public hospital in Hong Kong. PARTICIPANTS: All women who held the People's Republic of China passport or the two-way permit and those non-eligible persons whose spouses were Hong Kong Identity Card holders, who delivered in Kwong Wah Hospital from 1 April 2011 to 31 March 2012. RESULTS: Overall, 219 women who were non-eligible persons delivered 221 live births during the study period. Compared with the annual statistics of Kwong Wah Hospital in 2011, non-local mothers were of higher parity; more likely to have hypertensive disease (including pre-eclamptic toxaemia), preterm deliveries (ie at <37 weeks), babies needing admission to the special care baby unit, and macrosomic babies (ie weighing >4.0 kg). The rates of induction of labour and caesarean section were lower in this group. There was no significant difference in the maternal and neonatal outcomes between women who had no booking and those who had a booking in another Hospital Authority or private hospital. There were many incidents of near-miss obstetric complications or suboptimally managed obstetric conditions due to lack of well-structured and continuous antenatal care in this group of non-eligible persons. CONCLUSION: Non-eligible person delivering babies in Hong Kong has become a social obstetrics phenomenon. Despite the introduction of policies, reduction in the number of deliveries (quantity) did not improve the obstetric outcomes (quality). Health care professionals should continue to be prepared for managing the potential near-miss clinical complications in this group of 'travelling mothers'.

Insulin-stimulated glucose uptake and pathways regulating energy metabolism in skeletal muscle cells: the effects of subcutaneous and visceral fat, and long-chain saturated, n-3 and n-6 polyunsaturated fatty acids.

AIMS: The study aims to determine the effect of long-chain saturated and polyunsaturated (PUFA) fatty acids, specifically palmitic acid (PA; 16:0), docosahexaenoic acid (DHA; 22:6n-3) and linoleic acid (LA; 18:2n-6), and their interactions with factors from adipose tissue, on insulin sensitivity and lipid metabolism in skeletal muscle. METHODS: L6 myotubes were cultured with PA, DHA or LA (0.4mmol/l), with or without conditioned media from human subcutaneous (SC) and visceral (IAB) fat. Insulin-stimulated glucose uptake, lipid content, mRNA expression of key genes involved in nutrient utilization and protein expression of inhibitor protein inhibitor kappa B (IκB)-α and mammalian target of rapamycin (mTOR) were measured. RESULTS: PA and IAB fat reduced insulin-stimulated glucose uptake and their combined effect was similar to that of PA alone. PA-induced insulin resistance was ameliorated by inhibiting the de novo synthesis of ceramide, IκBα degradation or mTOR activation. The PA effect was also partially reversed by DHA and completely by LA in the presence of SC fat. PA increased diacylglycerol content, which was reduced by LA and to a greater extent when either IAB or SC fat was also present. PA increased SCD1 whereas DHA and LA increased AMPKα2 mRNA. In the presence of SC or IAB fat, the combination of PA with either DHA or LA decreased SCD1 and increased AMPKα2 mRNA. CONCLUSIONS: PA-induced insulin resistance in skeletal muscle involves inflammatory (nuclear factor kappa B/mTOR) and nutrient (ceramide) pathways. PUFAs promote pathways, at a transcriptional level, that increase fat oxidation and synergize with factors from SC fat to abrogate PA-induced insulin resistance.

SLICC/ACR damage index independently associated with left ventricular diastolic dysfunction in patients with systemic lupus erythematosus.

Left ventricular (LV) diastolic dysfunction has been reported in both active and inactive systemic lupus erythematosus (SLE) patients without clinical evidence of cardiovascular disease. However, the relationship between the long-term inflammatory burden reflected by the SLICC/ACR damage index and LV diastolic function has not been studied. Eighty-two SLE patients and 82 controls matched for age, sex, body mass index, blood pressure and heart rate underwent echocardiography with tissue Doppler imaging (TDI). LV diastolic function was estimated by the myocardial early diastolic velocity (E') at the lateral annulus. There were 51 patients (62.2%) with nephritis, 23 patients (28.0%) with hypertension, 21 patients (25.6%) with vasculitis, 16 patients (19.5%) with pulmonary hypertension, 4 patients (4.9%) with cerebrovascular disease and 2 patients (2.4%) with diabetes mellitus. Sixty-two patients (75.6%) were taking prednisone and 35 patients (42.7%) used a immunosuppressant. Forty-five patients (54.8%) had active disease and suffered from disease-related end-organ damage. Patients with SLICC/ACR damage index ≥1 had more evidence of LV diastolic dysfunction with lower lateral annulus E' (9.6 ± 3.4 vs 12.9 ± 3.5 cm/s, p < 0.001) than those without. In addition, the proportion of patients with abnormal LV myocardial relaxation (defined as lateral E' < 10.0 cm/s) (51.1% vs 16.2%, χ(2) = 10.8, p = 0.001) were significantly higher. Multivariate analysis showed that the SLICC/ACR damage index ≥1 was independently associated with LV diastolic dysfunction (OR = 3.80, 95%CI: 1.21-11.95, p = 0.023) after adjusting for hypertension, disease duration and medical therapy. This may suggest that the overall inflammatory burden in SLE, as reflected by SLICC/ACR damage index, is associated with the development of diastolic dysfunction in SLE patients.

Successful treatment of severe fetal chylothorax resistant to repeated pleuroamniotic shunting by OK-432 pleurodesis.

We report the first case of successful fetal pleurodesis with OK-432 for recurrent severe fetal primary chylothorax after failing repeated pleuroamniotic shunting. Shunting and pleurodesis could be complementary to each other in the treatment of fetal chylothorax.

Effects of Senior Simulation Suit Programme on nursing students' attitudes towards older adults: A randomized controlled trial.

BACKGROUND: As populations age worldwide, nursing educational institutions need to train nurses not only to provide health care services specific to the elderly, but also to have a positive attitude as they work. The present study aimed to investigate the efficacy of a Senior Simulation Suit Programme (SSSP). The SSSP, which focused on mimicking the physiological experiences of an 80 year-old person, was hypothesized to increase the wearer's positive attitude towards older adult care. METHODS: A single-blinded, randomized controlled trial was used to evaluate the efficacies of SSSP. One hundred and thirty-nine (139) nursing students were randomly assigned to either SSSP group (n = 69) or to a control group (n = 70) with "placebo clothing", i.e. clothing that mimicked old age but did not actually impair faculties. Two instruments-Kogan Attitudes Towards Old People Scale (KAOP) and a 1-item scale on Willingness To Care for Older People Scale (WCOP)-were used for data collection at baseline and at completion of SSSP. A Chinese version of Palmore's Facts Aging Quiz (C-FAQ) was used to assess nursing students' knowledge about adult care, and a questionnaire was developed to collect demographic information at baseline. RESULTS: No significant difference between the two groups was found. A significant increase of positive attitudes and of willingness to serve older adults was found in both the control group and the group wearing SSSP. CONCLUSION: Both the SSSP and control intervention could improve the attitudes of nursing students towards older adult care. This study suggests that wearing whatever the nursing students associate with being old, will improve their attitude towards older adult care.

Diagnosis of 5alpha-reductase 2 deficiency: a local experience.

5Alpha-reductase 2 deficiency is an autosomal recessive disorder characterised by lack of masculinisation in XY individuals due to failure to convert testosterone to dihydrotestosterone, the bioactive androgen. Traditionally, the testosterone-to-dihydrotestosterone ratio is used to diagnose this condition but interpreting these results is not always straightforward, thus they may be inconclusive. On the contrary, urinary steroid profiling unambiguously demonstrates a significantly reduced excretion of 5alpha-reduced steroid metabolites compared to their 5beta counterparts. This analytical technique can also simultaneously confirm or rule out other causes of ambiguous genitalia due to steroidogenic defects. Making a DNA-based diagnosis by studying the SRD5A2 gene has become increasingly popular. Here, we report six Chinese patients from different families who were all diagnosed with 5alpha-reductase 2 deficiency based on urinary steroid profile findings and mutational analysis of the SRD5A2 gene. R227Q was the most commonly identified mutation in these patients. Management of sexual development disorders is also discussed.

Study of gene-gene interactions for endophenotypic quantitative traits in Chinese asthmatic children.

BACKGROUND: Asthma is a complex disease resulting from interactions between multiple genes and environmental factors. Study of gene-gene interactions could provide insight into the pathophysiology of asthma. METHODS: We investigated the interactions among 18 single-nucleotide polymorphisms in eight candidate genes for plasma total immunoglobulin E (IgE) concentration and peripheral blood (PB) eosinophil count in 298 Chinese asthmatic children and 175 controls. Generalized multifactor dimensionality reduction and generalized linear model were used to analyze gene-gene interactions for the quantitative traits. RESULTS: A significant interaction was found between R130Q in IL13 and I50V in IL4RA for plasma total IgE concentration, with a cross-validation (CV) consistency of nine of 10 and a prediction error of 41.1% (P = 0.013). Plasma total IgE concentration was significantly higher in the high-risk than the low-risk groups (P < 0.0001). For PB eosinophil count, significant interaction was found between C-431T in TARC and RsaI_in2 in FCERIB, with a CV consistency of nine of 10 and a prediction error of 40.2% (P = 0.009). PB eosinophil count was significantly higher in the high-risk group than the low-risk groups (P < 0.0001). Generalized linear model also revealed significant gene-gene interaction for the above two endophenotypes with P = 0.013 for plasma total IgE concentration and P = 0.029 for PB eosinophil count respectively. CONCLUSIONS: Our data suggest significant interactions between IL13 and IL4RA for plasma total IgE concentration, and this is the first report to show significant interaction between TARC and FCERIB for PB eosinophil count in Chinese asthmatic children.

Indirect calorimetry: an indispensable tool to understand and predict obesity.

Obesity is a physiological condition of chronic positive energy balance. While the regulation of energy metabolism varies widely among individuals, identifying those who are metabolically prone to weight gain and intervening accordingly is a key challenge for reversing the course of the obesity epidemic. Indirect calorimetry is the most commonly used method to measure energy expenditure in the research setting. By measuring oxygen consumption and carbon dioxide production, indirect calorimetry provides minute-by-minute energy expenditure data that makes it the most valuable tool to distinguish the various components of energy expenditure, that is, sleeping and resting metabolic rate, thermic effect of food and the energy cost of activity. Importantly, such measures also provide information on energy substrate utilization. Here we summarized some of the research that revealed resting metabolic rate, spontaneous physical activity and respiratory quotient as key metabolic predictors of weight gain and obesity. Recent studies using indirect calorimetry in response to mid-term fasting or overfeeding have identified 'thrifty' and 'spendthrift' phenotypes in people who differ in propensity to weight gain. We propose the use of indirect calorimetry data as a basis for personalized interventions that may be efficacious in slowing down the rise of global obesity.

Triple-A syndrome--the first Chinese patient with novel mutations in the AAAS gene.

We report on the first Chinese patient with triple-A syndrome, who presented at 22 months with status epilepticus secondary to hyponatraemia and hypoglycaemia. Subsequent endocrine investigations confirmed primary adrenal insufficiency and aldosterone deficiency. In the presence of achalasia and alacrima, this patient satisfies the diagnostic criteria of triple-A syndrome. Further molecular testing detected compound heterozygous mutations in the AAAS gene: a c.580C --> T transition in exon 7 and a c.771delG single nucleotide deletion in exon 8. Testing of parents and brother confirmed their heterozygous carrier status.

An unusual case of non-malignant superior vena cava obstruction.

An 81-year-old Chinese woman presented with a 1-week history of increasing facial puffiness. She had 2:1 second-degree heart block and a permanent pacemaker that had been inserted 3 years previously because of syncopal episodes. Physical examination revealed facial plethora, dilated upper trunk veins, and oedematous upper limbs suggestive of superior vena cava obstruction syndrome. This was confirmed on urgent computed tomographic scan of the thorax. There was no evidence of extrinsic compression or formation of intraluminal thrombus. The underlying aetiology was a pacemaker-induced fibrotic stricture that was successfully treated with balloon venoplasty. At 3-month follow-up, the patient remained symptom-free with normal pacemaker function.

Recurrent and novel mutations of GCDH gene in Chinese glutaric acidemia type I families.

Glutaric acidemia type I is caused by mutations of the glutaryl-CoA dehydrogenase (GCDH) gene resulting in loss of GCDH enzyme activity. Patients present with progressive dystonia and lesions in basal ganglia. Dietary treatment, when instituted from the early neonatal period, markedly reduces dystonia and morbidity. Early diagnosis and prenatal diagnosis will be facilitated by knowledge of locally prevalent GCDH mutations. Several common GCDH mutations have been found in different ethnic groups. GCDH mutations were studied in 5 Chinese glutaric acidemia type I families. We detected two novel recurrent mutations (A219T and IVS10-2A>C) which were found in two unrelated families. An asymptomatic carrier of IVS10-2A>C was also found on screening of 120 individuals. Other mutations were identified, including two other novel (R386G & IVS3+1G>A) and two known mutations (G178R & R355H). Fibroblasts from patients carrying the novel mutations were confirmed to be deficient for GCDH activity. This is the first report of GCDH mutations describing recurrent mutations in Chinese patients. The carrier rate of IVS10-2A>C may be particularly high in Chinese.

Epidemiology of diabetes mellitus in children in Hong Kong: the Hong Kong childhood diabetes register.

OBJECTIVES: To establish a registry for Chinese children with onset of type 1 (insulin dependent) diabetes mellitus before 15 years of age and to determine the incidence of childhood onset type 1 diabetes mellitus in Chinese children in Hong Kong. RESEARCH DESIGN AND METHODS: A registry was established in 1997 to collect childhood diabetes cases retrospectively from all districts in Hong Kong. The study included all newly diagnosed cases of diabetes with onset < 15 yr of age from 1st January 1984 to 31 December 1996. Primary ascertainment was based on review of medical records at all regional public hospitals in Hong Kong and survey of all the registered practitioners in Hong Kong. The secondary source of validation was made impractical, if not impossible, because of the recent implementation of the Personal Data Privacy Ordinance in Hong Kong. RESULTS: A total of 255 diabetic cases were identified, 227 type 1 diabetes mellitus (218 were Chinese), 18 type 2 diabetes mellitus and 11 secondary diabetes. 246 patients were Chinese and 9 non-Chinese. The age-standardized incidence of type 1 and type 2 diabetes mellitus in southern Chinese children in Hong Kong was 1.4/100,000/yr and 0.1/100,000/yr respectively for children < 15 yr of age during the study period. The incidence rates for type 1 diabetes were 0.9, 1.5 and 1.7 per 100,000/yr for 0-4 years, 5 to 9 years and 10 to 14 years age-groups respectively. The incidence for males was 1.2/100,000/yr and for females 1.7/100,000/yr. A significant increase in the incidence was demonstrated during the study period by simple linear regression (slope 0.14/100,000/year, r2 = 0.73, p = 0.0002) CONCLUSIONS: A diabetic registry is established in Hong Kong. This study documents a very low incidence rate of childhood type 1 diabetes mellitus in southern Chinese children in Hong Kong and we have seen an increasing incidence of the disease in the past 13 years.

The prevalence of domestic violence against pregnant women in a Chinese community.

OBJECTIVE: To study the incidence of domestic violence in pregnant women attending the antenatal clinic of a local teaching hospital. STUDY DESIGN: All pregnant women attending their first antenatal clinic in Tsan Yuk Hospital between 11th August and 3rd November, 1998 were interviewed by a designated research nurse (Y.Y.J.L.) using a standard questionnaire (Abuse Assessment Screen) to detect the incidence of domestic violence, the nature of violence, the frequency of violence and the perpetrator of abuse. Demographic factors of the abused group were compared with those of the non-abused group using student's t-test and chi-square test. RESULTS: Pregnant women (631) were interviewed; 113 of them (17.9%) had a history of abuse; 99 women (15.7%) had been abused in the last year; 27 of them (4.3%) had been abused during their current pregnancy; 59 women (9.4%) had been sexually abused in the last year. The husband was the perpetrator in the majority of cases. The nature of violence during pregnancy was mainly psychological in the form of threats of abuse without any physical injury. Risk factors included unplanned pregnancy (P = 0.002) and women with husbands/partners who were unemployed or manual workers (P < 0.05). Unexpectedly, domestic violence occurred more commonly in permanent local residents rather than new immigrants (P < 0.05). CONCLUSION: This is probably the first study on the incidence of domestic violence in pregnant women in a Chinese community. The incidence is comparable to that from American studies. Routine screening with structured questions during the antenatal visits is necessary in order to identify the abused women so as to prevent potential trauma and to interrupt existing abuse.

Obstructive sleep apnoea syndrome and obesity in children.

OBJECTIVE: To review data on children who have both obesity and obstructive sleep apnoea syndrome. DATA SOURCE: Pubmed and MEDLINE (Ovid) literature search using the following key words: obstructive sleep apnea syndrome, obesity, and children. STUDY SELECTION: Literature and data on obesity-associated obstructive sleep apnoea syndrome in children. DATA EXTRACTION: Review of relevant information and data. DATA SYNTHESIS: Different definitions of obesity and obstructive sleep apnoea syndrome in children were used in different studies, which made it difficult to compare results from different studies conducted in different countries. Nonetheless, obstructive sleep apnoea syndrome was found to be moderately prevalent among obese children-namely, 13% to 36%. The severity of obstructive sleep apnoea syndrome was positively related to the degree of obesity. Blood pressure was found to be elevated in obese children with obstructive sleep apnoea syndrome. Weight reduction is an effective treatment. CONCLUSION: Children with obesity and obstructive sleep apnoea syndrome face a double challenge. A holistic approach to management requires a clear understanding of how both problems interact.

Consensus statement on iodine deficiency disorders in Hong Kong.

This article reviews the available data on the study of iodine deficiency disorders in Hong Kong and to discuss the approach towards preventing such disorders in Hong Kong. The importance of iodine and iodine deficiency disorders is described, and the available data on the dietary iodine intake and urinary iodine concentration in different populations of Hong Kong are summarised and discussed. Dietary iodine insufficiency among pregnant women in Hong Kong is associated with maternal goitrogenesis and hypothyroxinaemia as well as neonatal hypothyroidism. Borderline iodine deficiency exists in the expectant mothers in Hong Kong. Women of reproductive age, and pregnant and lactating women should be made aware and educated to have an adequate iodine intake, such as iodised salt, as an interim measure. A steering group involving all stakeholders should be formed to advise on the strategy of ensuring adequate iodine intake, including universal iodisation of salt in Hong Kong. Continuous surveillance of iodine status in the Hong Kong population is necessary.