Hip fractures are preventable: a proposal for osteoporosis screening and fall prevention in older people.

Osteoporosis is highly prevalent but underdiagnosed and undertreated in Hong Kong. Fragility fractures associated with osteoporosis often result in loss of independence and increased mortality for home-dwelling patients, imposing a high socio-economic burden on society. This issue requires urgent attention given the rapid growth of the elderly population in Hong Kong by approximately 4.3% each year. To address this situation, a group of experts convened to discuss practical ways to reduce the burden of fractures and formulated three recommendations: first, all men (aged ≥70 years) and women (aged ≥65 years) should receive universal dual-energy X-ray absorptiometry assessment for osteoporosis. Second, all men (aged ≥70 years) and women (aged ≥65 years) with a fracture-risk assessment-derived 10-year risk (hip fracture with bone mineral density) ≥3% should receive ≥3 years of anti-osteoporotic treatment. Third, comprehensive structured assessment (including dual-energy X-ray absorptiometry) should be conducted in older patients with a history of falling. By implementing these recommendations, we estimate that we could prevent 5234 hip fractures in 10 years, an annual incidence reduction of approximately 7%, and save HK$425 million in direct medical costs plus substantial indirect savings. Ample clinical and cost-effectiveness data support these recommendations, and studies in Hong Kong and abroad could serve as models on how to implement them. We are confident that by applying these recommendations rigorously and systematically, a significant reduction in hip fractures in Hong Kong is achievable.

Concurrent beneficial (vitamin D production) and hazardous (cutaneous DNA damage) impact of repeated low-level summer sunlight exposures.

BACKGROUND: The concurrent impact of repeated low-level summer sunlight exposures on vitamin D production and cutaneous DNA damage, potentially leading to mutagenesis and skin cancer, is unknown. OBJECTIVES: This is an experimental study (i) to determine the dual impact of repeated low-level sunlight exposures on vitamin D status and DNA damage/repair (via both skin and urinary biomarkers) in light-skinned adults; and (ii) to compare outcomes following the same exposures in brown-skinned adults. METHODS: Ten white (phototype II) and six South Asian volunteers (phototype V), aged 23-59 years, received 6 weeks' simulated summer sunlight exposures (95% ultraviolet A/5% ultraviolet B, 1·3 standard erythemal doses three times weekly) wearing summer clothing exposing ~35% body surface area. Assessments made were circulating 25-hydroxyvitamin D [25(OH)D], immunohistochemistry for cyclobutane pyrimidine dimer (CPD)-positive nuclei and urinary biomarkers of direct and oxidative (8-oxo-deoxyguanosine) DNA damage. RESULTS: Serum 25(OH)D rose from mean 36·5 ± 13·0 to 54·3 ± 10·5 nmol L-1 (14·6 ± 5·2 to 21·7 ± 4·2 ng mL-1 ) in phototype II vs. 17·2 ± 6·3 to 25·5 ± 9·5 nmol L-1 (6·9 ± 2·5 to 10·2 ± 3·8 ng mL-1 ) in phototype V (P < 0·05). Phototype II skin showed CPD-positive nuclei immediately postcourse, mean 44% (range 27-84) cleared after 24 h, contrasting with minimal DNA damage and full clearance in phototype V (P < 0·001). The findings did not differ from those following single ultraviolet radiation (UVR) exposure. Urinary CPDs remained below the detection threshold in both groups; 8-oxo-deoxyguanosine was higher in phototype II than V (P = 0·002), but was unaffected by UVR. CONCLUSIONS: Low-dose summer sunlight exposures confer vitamin D sufficiency in light-skinned people concurrently with low-level, nonaccumulating DNA damage. The same exposures produce minimal DNA damage but less vitamin D in brown-skinned people. This informs tailoring of sun-exposure policies.

Sonographic measurement of mesenteric fat predicts presence of fatty liver among subjects with polycystic ovary syndrome.

OBJECTIVE: Visceral fat is believed to be important in the pathogenesis of metabolic syndrome and fatty liver. In this study, we examined the relationship between mesenteric fat thickness and other sonographic indices of adiposity and the presence of fatty liver among subjects with polycystic ovary syndrome (PCOS). SUBJECTS AND METHODS: A total of 117 Chinese subjects with PCOS were evaluated (mean age, 28.6 ± 6.5 yr; mean body mass index, 24.3 ± 5.3 kg/m(2)). Anthropometric measurements and metabolic risk profile, including a standard oral glucose tolerance test, were assessed in all subjects. All subjects underwent an ultrasound examination for measurement of thickness of mesenteric, preperitoneal, and sc fat as well as evaluation for fatty liver. RESULTS: Forty-six (39.3%) of the subjects had fatty liver. PCOS subjects with fatty liver had higher body mass index, waist circumference, waist-hip ratio, and systolic blood pressure; a more unfavorable lipid profile with higher triglyceride; lower high-density lipoprotein cholesterol; higher fasting glucose and insulin; higher 2-h glucose during oral glucose tolerance test; lower SHBG; and higher alanine aminotransferase. Subjects with fatty liver had increased thickness of preperitoneal, mesenteric, and sc fat, as well as increased carotid intima-media thickness. Abdominal fat thickness showed moderate correlation to alanine aminotransferase as well as fasting insulin. On multivariate logistic regression, fasting insulin and mesenteric fat thickness were identified as independent predictors of fatty liver among subjects with PCOS. CONCLUSION: Fatty liver is present in a significant proportion of Chinese patients with PCOS. Sonographic measurement of mesenteric fat is an independent determinant of fatty liver among subjects with PCOS and identifies subjects at increased cardiovascular risk.

The endocannabinoid 2-arachidonoylglycerol (2-AG) and metabolizing enzymes during rat fetoplacental development: a role in uterine remodelling.

The main endocannabinoids (EC) identified in mammalian tissues are N-arachidonoylethanolamide (AEA, anandamide), and 2-arachidonoylglycerol (2-AG). AEA levels are critical in pregnancy, especially during implantation, decidualization, and placental development. As 2-AG functions in pregnancy are still largely undefined, we hypothesized that it may also have a role during fetoplacental development. We showed that 2-AG is not only present in the rat mesometrial decidua and plasma during fetoplacental development, but that both 2-AG synthesizing (diacylglycerol lipase) and degradation (monoacylglycerol lipase) enzymes are expressed by decidual cells. While lower concentrations of 2-AG induced apoptosis of rat primary decidual cells, via the CB1 receptor, higher concentrations induced a dramatic effect on cell morphology, cell viability and lactate dehydrogenase release, triggered through a mechanism independent of CB1. This study provides evidences that 2-AG fluctuation in maternal tissues throughout normal pregnancy is primarily regulated by its metabolizing enzymes. Together, these data supports the hypothesis that a deregulation of the endocannabinoid system through aberrant cannabinoid signalling may impact normal uterine remodelling process and consequently normal pregnancy.

N-acylethanolamine levels and expression of their metabolizing enzymes during pregnancy.

Decidualization is essential for a successful pregnancy and is a tightly regulated process influenced by the local microenvironment. Lipid-based mediators, such as the endocannabinoid anandamide, and other compounds that have cannabimimetic actions may act on the decidua during early pregnancy. In this study, the levels of N-arachidonoylethanolamine (anandamide) and two other N-acylethanolamines, N-oleoylethanolamine and N-palmitoylethanolamine, were measured in rat plasma and maternal tissues between d 8 and 19 of pregnancy by ultraperformance liquid chromatography tandem mass spectrometry. The spatiotemporal expression of N-acylethanolamine metabolizing enzymes in implantation units were also determined by quantitative PCR, Western blot, and immunohistochemistry and shown to vary with gestation being mainly localized in decidual cells. The data also indicated that plasma and tissues levels of all three N-acylethanolamines fluctuate throughout pregnancy. Tissue levels of endocannabinoids did not correlate with plasma, suggesting that during pregnancy, maternal tissue levels of endocannabinoids are primarily regulated by in situ production and degradation to create endocannabinoid gradients conducive to successful pregnancy.

The plasma levels of the endocannabinoid, anandamide, increase with the induction of labour.

OBJECTIVE: Plasma anandamide (AEA) levels have previously been shown to be elevated in labour and defective cannabinoid receptor type 1 signalling in mice has been shown to be associated with elevation of corticotrophin-releasing hormone and spontaneous onset of preterm labour. We measured plasma AEA levels in women undergoing induction of labour to define the changes during the transition from the nonlabouring to labouring state. DESIGN: A longitudinal observational study. SETTING: A large UK teaching hospital. POPULATION: Term pregnant women undergoing induction of labour. METHODS: Blood was collected from women before induction of labour and again when they were in active labour. Plasma AEA was extracted and measured using ultraperformance liquid chromatography-tandem mass spectrometry. MAIN OUTCOME MEASURES: The primary outcome variable was change in plasma AEA levels from the nonlabouring to the labouring state. The secondary outcome was induction-to-delivery interval. RESULTS: There was a 1.5-fold increase in mean plasma AEA levels from 1.20 +/- 0.57 nm in the nonlabouring state to 1.82 +/- 0.87 nm in the labouring state (P < 0.0001). Induction-to-delivery interval was predicted by both Bishop's score (P < 0.0001) and percentage change in plasma AEA levels (P < 0.0001). There was a negative correlation between the percentage change in plasma AEA level and the induction-to-delivery interval (r = - 0.28; P = 0.0481). This means that the greater the rise in the plasma AEA levels the shorter the duration of labour. CONCLUSIONS: Plasma AEA levels increase with active labour and the negative correlations between percentage change in plasma AEA levels and induction-to-delivery interval suggest that AEA is likely to be involved in the physiological mechanisms of labour. Whether this increase is essential for myometrial contraction is unclear and needs further investigation.

A randomized, double-blind, placebo-controlled study of the effect of a Chinese herbal medicine preparation (Dang Gui Buxue Tang) on menopausal symptoms in Hong Kong Chinese women.

OBJECTIVE: Many complementary or alternative medicines are being used for the treatment of menopausal symptoms but most have not been properly tested for efficacy or for safety. This study examined the effect of a Chinese herbal preparation (Dang Gui Buxue Tang) on menopausal symptoms in Hong Kong Chinese women. METHODS: A 6-month randomized, double-blind, placebo-controlled study of the effect of Dang Gui Buxue Tang (a 1 : 5 combination of Dang Gui (Angelicae sinensis) and Huang Qi (Astragalus membranaceus)) on acute menopausal symptoms. A total of 103 symptomatic women were enrolled. Three failed to meet inclusion criteria, leaving 50 subjects for inclusion in each group. RESULTS: Overall, mild hot flushes were reported more frequently than either moderate or severe flushes. In analysis by severity of flushes, there was a significant reduction in the number of mild hot flushes per month in the treatment group but not in the placebo group (from 18.9 +/- 23.5 at baseline to 8.6 +/- 17.1 at 6 months in the treatment group (p < 0.01) and from 26.0 +/- 43.5 to 12.4 +/- 17.6 in the placebo group (p = 0.062)). For moderate flushes, there was a significant reduction in the placebo group compared with the treatment group (from 18.9 +/- 28.7 at baseline to 11.1 +/- 29.9 at 6 months in the placebo group (p < 0.05) and from 10.5 +/- 22.3 to 6.0 +/- 16.0 in the treatment group (p = 0.107)). There was no significant change in either treatment or placebo groups in the reporting of severe hot flushes. Episodes of night sweats decreased significantly in the placebo but not in the treatment group (from 6.8 +/- 10.0 at baseline to 1.9 +/- 5.7 at 6 months in the placebo group (p < 0.05) and from 5.4 +/- 8.9 to 3.2 +/- 8.5 in the treatment group (p = 0.471)). In the vasomotor domain of the Menopause Specific Quality of Life, there was a significant reduction in scoring in the placebo group (from 2.8 +/- 1.6 to 1.7 +/- 1.3, p < 0.01) but not in the treatment group (from 2.8 +/- 2.1 to 2.3 +/- 1.6, p = 0.247). CONCLUSIONS: This study found overall no significant difference between Dang Gui Buxue Tang and placebo in the treatment of vasomotor symptoms in Hong Kong Chinese women. The frequency of mild, moderate and severe hot flushes decreased in both treatment and placebo groups, but Dang Gui Buxue Tang was statistically superior to placebo only in the treatment of mild hot flushes. There were no serious adverse events attributable to treatment during the study period.

Cardiovascular risks and metabolic syndrome in Hong Kong Chinese women with polycystic ovary syndrome.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) frequently exhibit central obesity, glucose intolerance, atherogenic dyslipidaemia and hypertension which are characteristic features of the metabolic syndrome (MetS). METHODS: A total of 295 premenopausal Chinese women with PCOS diagnosed by the Rotterdam criteria (mean age: 30.2 +/- 6.4 years) and 98 control subjects without PCOS were evaluated for prevalence of MetS and cardiovascular risk factors, including dyslipidaemia and dysglycaemia. RESULTS: Using the 2005 modified Adult Treatment Panel III criteria, MetS (presence of three or more risk factors) was found in 24.9% of PCOS women compared to 3.1% of controls. The prevalence of MetS in PCOS women increased from 16.7% at under 30 years of age to 53.3% at over 40 years. MetS was also more prevalent in overweight and obese (41.3%) than normal-weight PCOS women (0.9%). However, multivariate regression analysis showed that women with PCOS had a 5-fold increase in risk of MetS (odds ratio 4.90; 95% confidence interval: 1.35-17.84) compared with women without PCOS even after controlling for age and BMI, suggesting PCOS alone is an independent risk factor for MetS. CONCLUSIONS: There is high prevalence of MetS in Hong Kong Chinese women with PCOS despite their relatively young age. Recognition of these cardiometabolic risk factors requires a high level of awareness in conjunction with early and regular screening.

Expression of a novel T-complex testis expressed 5 (Tctex5) in mouse testis, epididymis, and spermatozoa.

Expression of T-complex testis expressed 5 (Tctex5), an orthologue of protein phosphatase-1 inhibitor-3 (PPP1R11), was enhanced in mouse testis and was also expressed in epididymis and spermatozoa. There were three transcripts of Tctex5 including one brain specific and two common transcripts dominant in mouse testis. Tctex5 protein isoforms (75, 52, 32, 25, and 14.3 kDa) were identified. Isoforms of 75 and 52 kDa were spermatogenic-specific and were found in protein fraction containing nuclei, mitochondria, and flagellum accessory, and also in protein fraction containing mainly membranes. Tctex5 was localized in nuclei of pachytene spermatocytes, round spermatocytes, cytoplasm of Sertoli cells in testis; cilia, secretion bodies and nuclei of epithelial cells and interstitium smooth muscle cells in epididymis; and head and principal piece of tail in epididymal spermatozoa. The results suggested that Tctex5 might be a specific protein phosphatase-1 inhibitor in sperm; various Tctex5 transcripts and isoforms and cellular locations imply its different roles in spermatogenesis. Nuclei-type isoforms (75 and 52 kDa) might take part in nucleus remodeling during spermatogenesis whilst membrane-type isoform (52 kDa) might be responsible for dephosphorylation of proteins during capacitation. The other isoforms might play general roles for all kinds of cell types.

Polycystic ovarian syndrome in Hong Kong Chinese women: patient characteristics and diagnostic criteria.

OBJECTIVES: To identify the characteristics of Hong Kong Chinese women with polycystic ovarian syndrome and to compare different diagnostic criteria. DESIGN: Retrospective study. SETTING: Gynae-endocrinology Clinics in the Prince of Wales Hospital, Hong Kong. PATIENTS: Ninety Hong Kong Chinese women with polycystic ovarian syndrome who were diagnosed according to the hospital's criteria. MAIN OUTCOME MEASURES: Prevalence of typical features of polycystic ovarian syndrome, including anovulation and hyperandrogenism (with other endocrine causes excluded), polycystic ovarian features on ultrasonography, luteinising hormone predominance, obesity, and insulin resistance. RESULTS: Almost all (98.9%) patients with polycystic ovarian syndrome presented with anovulation, only 48.9% of them had clinical or biochemical evidence of hyperandrogenism. Typical ultrasound appearances of polycystic ovaries were observed in 86.7% of patients. Luteinising hormone predominance and insulin resistance were demonstrated in 67.8% and 40.7% of the cohort, respectively. Eight-six (95.6%) patients should have also been diagnosed with polycystic ovarian syndrome based on the 2003 Rotterdam new criteria. About 60% of patients who screened positive for insulin resistance had normal fasting serum glucose levels. The same proportion who had full screening for insulin resistance by oral glucose tolerance tests and fasting serum glucose to insulin ratios had discordant results of these two tests. CONCLUSIONS: The 2003 Rotterdam new diagnostic criteria for polycystic ovarian syndrome are generally applicable to the Hong Kong Chinese population. Early detection of insulin resistance in patients with polycystic ovarian syndrome can be ensured by performing an oral glucose tolerance test combined with measurement of fasting serum glucose to insulin ratio.

Characterization and comparison of recombinant human and rat TRPV1 receptors: effects of exo- and endocannabinoids.

BACKGROUND: TRPV1 is a ligand-gated ion channel whose activation by capsaicin increases intracellular Ca(2+) ([Ca(2+)](i)). TRPV1 and cannabinoid CB(1) receptor activation are capable of eliciting analgesia. In this study, using recombinant human (h) and rat (r) TRPV1 receptors expressed in HEK293 cells, we have performed a comparison of both TRPV1 species at 22 and 37 degrees C and compared endo- and exocannabinoid activity at both receptors. METHODS: [Ca(2+)](i) was measured in Fura-2-loaded HEK293(hTRPV1) and HEK293(rTRPV1) cells. To assess native CB(1) receptor activity, [(35)S]GTPgammaS binding to membranes prepared from rat cerebellum was measured. RESULTS: Both capsaicin (pEC(50) rat approximately 6.9 and pEC(50) human approximately 6.8 at 37 degrees C) and anandamide (pEC(50) rat approximately 5.3 and pEC(50) human approximately 5.8 at 37 degrees C) produced a concentration-dependent increase in [Ca(2+)](i) in rat and human systems and at 22 and 37 degrees C. In HEK293(rTRPV1) cells, anandamide appeared to be a partial agonist. Capsazepine demonstrated competitive antagonism at both human and rat TRPV1 receptors and at both temperatures studied. Capsazepine effects were not temperature dependent: pK(B) at rTRPV1 was 5.98 at 22 degrees C and 6.02 at 37 degrees C, and pK(B) at hTRPV1 was 6.76 at 22 degrees C and 6.75 at 37 degrees C. However, there was a consistent 6-fold increase in capsazepine potency for hTRPV1 relative to rTRPV1. The exocannabinoid Delta(9)-tetrahydrocannabinol failed to increase [Ca(2+)](i), although its solvent ethanol was an effective TRPV1 activator. In the [(35)S]GTPgammaS binding assay using rat cerebellar membranes, anandamide (pEC(50) approximately 5.8) and Delta(9)-tetrahydrocannabinol (pEC(50) approximately 7.1), but not capsaicin, stimulated binding. Delta(9)-tetrahydrocannabinol was a partial agonist. pEC(50) values for anandamide at rTRPV1 and rCB(1) were similar. CONCLUSIONS: There were small differences in the pharmacology of rat and human TRPV1 receptors. Whilst capsaicin activated TRPV1 and Delta(9)-tetrahydrocannabinol activated CB(1), anandamide is an endogenous agonist for both receptor systems.

Psychological well-being and the dyadic relationship of Chinese menopausal women (and their spouses) attending hormone replacement clinics.

This survey examined the general health and the marital relationship of 122 Chinese menopausal women and their spouses attending hormone replacement clinics. Climacteric symptoms of the participants were assessed by the modified Greene Climacteric Scale (GCS). The psychological well-being of the participants and their spouses was assessed by the 12-item Chinese General Health Questionnaire (GHQ), and their marital quality was assessed by the Chinese Dyadic Adjustment Scale (DAS). The GCS scores of our cohort were significantly higher than that of a community-based sample of menopausal Chinese women. About one-third of the participants and one-fifth of their spouses suffered from reduced psychological well-being. Although the DAS total scores of the participants and their spouses were comparable to those of the adjusted couples in a younger population, the affectional DAS subscores were significantly lower. The GCS scores of the menopausal women were significantly positively correlated with their GHQ scores but negatively correlated with their DAS scores. In summary, the menopausal women attending the hormonal replacement clinics, especially those with more dimacteric symptoms, suffered from significant psychiatric morbidity and marital maladjustment. The psychological dimension of the menopause should never be neglected.

Revisit of metformin treatment in polycystic ovarian syndrome.

Polycystic ovary syndrome (PCOS) is a common endocrinopathy in women; its traditional pharmacological therapy mainly addresses short-term symptom control and does not correct the associated long-term metabolic risks. Recently, there has been increasing evidence that insulin resistance has an important implication in the pathogenesis of PCOS and that insulin-sensitizing drugs are a useful therapeutic approach. Therefore this review aims to discuss the current evidence on the use of metformin, a commonly used insulin-sensitizing agent, in treating both the short-term and the long-term problems of women with PCOS.

Intravenous leiomyomatosis with atypical histologic features: a case report.

Intravenous leiomyomatosis (IVL) is a rare smooth muscle tumor. We report a case of IVL with atypical histologic features, which did not respond to gonadotropin-releasing hormone agonists and could be only partially resected due to adherence to the vessel wall. Atypical histology may signify more aggressive behavior. IVL should always be considered when a patient presents with both uterine leiomyoma and venous thrombosis, and a high index of suspicion is crucial for early diagnosis. An adequate surgical preparation including venous graft or prosthetic reconstruction is essential as difficulty in removal may arise if the intravascular tumor adheres to the vessel wall.

Effects of the intensity of downregulation on outcome of in vitro fertilization and embryo transfer.

Gonadotropin releasing hormone agonists (GnRHa) are commonly used during in vitro fertilization and embryo transfer (IVF/ET) treatment cycles to downregulate the hypothalamic-pituitary-ovarian axis prior to ovarian stimulation with gonadotropins. It has been suggested that profound downregulation may have an adverse effect on IVF/ET outcome. The aim of this study was to examine the relationship between the degree of downregulation and IVF/ET outcome. A retrospective analysis was performed on 151 IVF/ET cycles conducted over a six month period. Intensity of downregulation was assessed using measurements of serum concentrations of luteinizing hormone (LH) and estradiol (E2) made at the end of a two week downregulation period. There was no correlation between serum concentration of LH (whether used alone or in combination with E2) and IVF/ET pregnancy rates. However, those subjects who were more suppressed according to the E2 concentration (< 148 pmol/l, [median]) required significantly more gonadotropins (3306 IU versus 2863 IU, p < 0.05) and took longer for follicles to reach maturity (10.9 days versus 9.7 days, p < 0.05). They also had a lower pregnancy rate per embryo transfer (10.4% versus 28.6%, p < 0.05) compared with those having a higher basal E2 concentration. We conclude from this study that the basal serum E2 concentration rather than the LH concentration is a more sensitive indicator of the intensity of downregulation by GnRHa and it may be a better predictor of IVF outcome.

Relationship between birthweight and repeated courses of antenatal corticosteroids.

A retrospective study was conducted in a university teaching hospital to review the association between birthweight and the number of courses of antenatal corticosteroids received in 236 singleton pregnancies. Those pregnancies complicated with pregnancy-induced hypertension, preeclampsia, diabetes mellitus and intrauterine growth restriction were excluded. The results showed that the birthweight ratio (calculated as the baby's birthweight divided by the median birthweight for that gestational age) was negatively correlated with the number of courses of corticosteroids received. Further, exposure to four or more courses of antenatal corticosteroids was associated with a significant reduction in birthweight ratio and a three-fold increase in the risk of being small-for-dates compared to those exposed to one to three courses.