The association of coffee consumption with the risk of osteoporosis and fractures: a systematic review and meta-analysis.

To elucidate the association of coffee and bone health would help fracture risk reduction via dietary intervention. Although those who had higher coffee consumption were less likely to have osteoporosis, the associations between coffee consumption and fracture risk need further investigations with better study designs. INTRODUCTION: The associations between coffee consumption and the risk of osteoporosis and fracture remain inconclusive. We aimed to better quantify these associations by conducting meta-analyses of observational studies. METHODS: Relevant studies were systematically searched on PubMed, Web of Science, Cochrane library, and Embase Database up to November 25, 2021. The odds ratio (OR) or relative risk (RR) with 95% confidence intervals (CI) was pooled and a dose-response analysis was performed. RESULTS: Four studies with 7114 participants for osteoporosis and thirteen studies with 391,956 participants for fracture incidence were included in the meta-analyses. High versus low coffee consumption was associated with a lower risk of osteoporosis [pooled OR (95% CI): 0.79 (0.65-0.92)], while it was non-significantly associated with fracture incidence [pooled OR (95% CI): 0.86 (0.67-1.05) at hip and 0.89 (0.42-1.36) at non-hip]. A non-linear association between the level of coffee consumption and hip fracture incidence was shown (P = 0.004). The pooled RR (95% CI) of hip fracture risk in those who consumed 1, 2-3, 4, and ≥ 9 cups of coffee per day was 0.92 (0.87-0.97), 0.89 (0.83-0.95), 0.91 (0.85-0.98), and 1.10 (0.76-1.59), respectively. The significance in the association between coffee consumption and the hip fracture incidence decreased in those studies that had larger sample size, higher quality, and more adjustments. CONCLUSIONS: A dose-dependent relationship may exist between coffee consumption and hip fracture incidence. The effect of high versus low coffee consumption was influenced by study designs. Further studies with dedicated designs are needed to confirm the independent effects of coffee consumption on bone health.

Anaesthesia for mechanical thrombectomy: a narrative review.

Stroke is a leading cause of death and disability, and is associated with a huge societal and economic burden. Interventions for the immediate treatment of ischaemic stroke due to large vessel occlusion are dependent on recanalisation of the occluded vessel. Trials have provided evidence supporting the efficacy of mechanical thrombectomy in ischaemic stroke due to large vessel occlusion. This has resulted in changes in management and organisation of stroke care worldwide. Major determinants of effectiveness of thrombectomy include: time between stroke onset and reperfusion; location of occlusion and local collateral perfusion; adequacy of reperfusion; patient age; and stroke severity. The role of anaesthetic technique on outcome remains controversial with published research showing conflicting results. As a result, choice of conscious sedation or general anaesthesia for mechanical thrombectomy is often dependent on individual operator choice or institutional preference. More recent randomised controlled trials have suggested that protocol-driven general anaesthesia is no worse than conscious sedation and may even be associated with better outcomes. These and other studies have highlighted the importance of optimal blood pressure management as a major determinant of patient outcome. Anaesthetic management should be tailored to the individual patient and circumstances. Acute ischaemic stroke is a neurological emergency; clinicians should focus on minimising door-to-groin puncture time and the provision of high-quality periprocedural care with a particular emphasis on the maintenance of an adequate blood pressure.

Effectiveness of a childbirth massage programme for labour pain relief in nulliparous pregnant women at term: a randomised controlled trial.

INTRODUCTION: The effect of massage for pain relief during labour has been controversial. This study investigated the efficacy of a programme combining intrapartum massage, controlled breathing, and visualisation for non-pharmacological pain relief during labour. METHODS: This randomised controlled trial was conducted in two public hospitals in Hong Kong. Participants were healthy low-risk nulliparous Chinese women ≥18 years old whose partners were available to learn massage technique. Recruitment was performed at 32 to 36 weeks of gestation; women were randomised to attend a 2-hour childbirth massage class at 36 weeks of gestation or to receive usual care. The primary outcome variable was the intrapartum use of epidural analgesia or intramuscular pethidine injection. RESULTS: In total, 233 and 246 women were randomised to the massage and control groups, respectively. The use of epidural analgesia or pethidine did not differ between the massage and control groups (12.0% vs 15.9%; P=0.226). Linear-by-linear analysis demonstrated a trend whereby fewer women used strong pharmacological pain relief in the massage group, and a greater proportion of women had analgesic-free labour (29.2% vs 21.5%; P=0.041). Cervical dilatation at the time of pethidine/epidural analgesia request was significantly greater in the massage group (3.8 ± 1.7 cm vs 2.3 ± 1.0 cm; P<0.001). CONCLUSION: The use of a massage programme appeared to modulate pain perception in labouring women, such that fewer women requested epidural analgesia and a shift was observed towards the use of weaker pain relief modalities; in particular, more women in the massage group were analgesic-free during labour.

Secondary data analysis investigating effects of marine omega-3 fatty acids on circulating levels of leptin and adiponectin in older adults.

BACKGROUND: Higher leptin and lower adiponectin levels have been linked to progressing systemic inflammation and diseases of aging. Among older adults with obesity and an inflammatory conditions, we quantified effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation on leptin, adiponectin, and the leptin-to-adiponectin ratio (LAR). We also examined associations among adipokine and cytokine levels. METHODS: Using a randomized, double-blind, placebo-controlled design, participants (mean age 61.3 ± 2.1) received 1.5 g EPA + 1.0 g DHA (n = 14) or mineral oil (n = 18) daily. Plasma adipokine and cytokine levels were quantified by electrochemiluminescence at all study intervals. RESULTS: While no between-group differences were detected, there was a reduction in the LAR (by 23%, p=.065) between weeks 4 and 8 among the EPA+DHA group. Adiponectin levels were negatively associated with IL-1ß levels at week 4 (p=.02) and TNF-α levels at week 8 (p=.03). CONCLUSION: Potential benefits of EPA+DHA supplementation among aging populations warrant further study.

A review of diagnosis and treatment of acne in adult female patients.

This review focuses on the treatment options for adult female patients with acne. Acne in adult female patients may start during adolescence and persist or have an onset in adulthood. Acne has various psychosocial effects that impact patients' quality of life. Treatment of acne in adult women specifically has its challenges due to the considerations of patient preferences, pregnancy, and lactation. Treatments vary widely and treatment should be tailored specifically for each individual woman. We review conventional therapies with high levels of evidence, additional treatments with support from cohort studies and case reports, complementary and/or alternative therapies, and new agents under development for the treatment of patients with acne.

Reduced bone mineral density in human immunodeficiency virus-infected individuals: a meta-analysis of its prevalence and risk factors: supplementary presentation.

A meta-analysis was conducted to evaluate the prevalence of osteopenia/osteoporosis in human immunodeficiency virus (HIV)-infected individuals. The prevalence of osteopenia/osteoporosis in HIV-infected and antiretroviral therapy (ART)-treated individuals was significantly higher than respective controls. Evidence regarding bone loss within first year of HIV infection or ART initiation was preliminary.

Design and development of low cost polyurethane biopolymer based on castor oil and glycerol for biomedical applications.

In the current study, we present the synthesis of novel low cost bio-polyurethane compositions with variable mechanical properties based on castor oil and glycerol for biomedical applications. A detailed investigation of the physicochemical properties of the polymer was carried out by using mechanical testing, ATR-FTIR, and X-ray photoelectron spectroscopy (XPS). Polymers were also tested in short term in-vitro cell culture with human mesenchymal stem cells to evaluate their biocompatibility for potential applications as biomaterial. FTIR analysis confirmed the synthesis of castor oil and glycerol based PU polymers. FTIR also showed that the addition of glycerol as co-polyol increases crosslinking within the polymer backbone hence enhancing the bulk mechanical properties of the polymer. XPS data showed that glycerol incorporation leads to an enrichment of oxidized organic species on the surface of the polymers. Preliminary investigation into in vitro biocompatibility showed that serum protein adsorption can be controlled by varying the glycerol content with polymer backbone. An alamar blue assay looking at the metabolic activity of the cells indicated that castor oil based PU and its variants containing glycerol are non-toxic to the cells. This study opens an avenue for using low cost bio-polyurethane based on castor oil and glycerol for biomedical applications.

The nasal mucosal late allergic reaction to grass pollen involves type 2 inflammation (IL-5 and IL-13), the inflammasome (IL-1ß), and complement.

Non-invasive mucosal sampling (nasosorption and nasal curettage) was used following nasal allergen challenge with grass pollen in subjects with allergic rhinitis, in order to define the molecular basis of the late allergic reaction (LAR). It was found that the nasal LAR to grass pollen involves parallel changes in pathways of type 2 inflammation (IL-4, IL-5 and IL-13), inflammasome-related (IL-1ß), and complement and circadian-associated genes. A grass pollen nasal spray was given to subjects with hay fever followed by serial sampling, in which cytokines and chemokines were measured in absorbed nasal mucosal lining fluid, and global gene expression (transcriptomics) assessed in nasal mucosal curettage samples. Twelve of 19 subjects responded with elevations in interleukin (IL)-5, IL-13, IL-1ß and MIP-1ß/CCL4 protein levels in the late phase. In addition, in these individuals whole-genome expression profiling showed upregulation of type 2 inflammation involving eosinophils and IL-4, IL-5 and IL-13; neutrophil recruitment with IL-1α and IL-1ß; the alternative pathway of complement (factor P and C5aR); and prominent effects on circadian-associated transcription regulators. Baseline IL-33 mRNA strongly correlated with these late-phase responses, whereas a single oral dose of prednisone dose-dependently reversed most nasal allergen challenge-induced cytokine and transcript responses. This study shows that the LAR to grass pollen involves a range of inflammatory pathways and suggests potential new biomarkers and therapeutic targets. Furthermore, the marked variation in mucosal inflammatory events between different patients suggests that in the future precision mucosal sampling may enable rational specific therapy.

Acute effects of a single dose of tocotrienols on insulinemic and inflammatory responses in metabolic syndrome subjects after a high-fat challenge.

BACKGROUND/OBJECTIVES: Evidence shows that tocotrienols potentially reverse various chronic disease progressions caused by the metabolic syndrome. We aimed to investigate the acute effects of a single-dose supplementation of gamma and delta tocotrienols (γδ-T3, 1:4 ratio) compared with those in placebo on the insulinemic, anti-inflammatory and anti-thrombogenic responses in metabolic syndrome subjects. SUBJECTS/METHODS: Thirty metabolic syndrome subjects (15 men and 15 women) were recruited to a randomized, double-blinded and crossover study. The subjects were administered a single dose of 200 mg or 400 mg γδ-T3 emulsions or placebo incorporated into a glass of strawberry-flavored milkshake, consumed together with a high-fat muffin. Blood samples were collected at 0, 5, 15, 30, 60, 90, 120, 180, 240, 300 and 360 min after meal intake. RESULTS: Plasma vitamin E levels reflected the absorption of γδ-T3 after treatments. Postprandial changes in serum C-peptide, serum insulin, plasma glucose, triacylglycerol, non-esterified fatty acid and adiponectin did not differ between treatments, with women displaying delayed increase in the aforementioned markers. No significant difference between treatments was observed for plasma cytokines (interleukin-1 beta, interleukin-6 and tumor necrosis factor alpha) and thrombogenic markers (plasminogen activator inhibitor type 1 and D-dimer). CONCLUSIONS: Supplementation of a single dose of γδ-T3 did not change the insulinemic, anti-inflammatory and anti-thrombogenic responses in metabolic syndrome subjects.

Inulin significantly improves serum magnesium levels in proton pump inhibitor-induced hypomagnesaemia.

BACKGROUND: Proton pump inhibitors (PPI) are among the most widely prescribed drugs to treat gastric acid-related disorders. PPI-induced hypomagnesaemia, a defect in intestinal absorption of Mg(2+) , can be a severe side effect of chronic PPI use. AIM: To restore serum Mg(2+) concentrations in PPI-induced hypomagnesaemia patients by dietary supplementation with inulin fibres. METHODS: Eleven patients with PPI-induced hypomagnesaemia and 10 controls were treated with inulin (20 g/day). Each trial consisted of two cycles of 14-day inulin treatment followed by a washout period of 14 days. Patients continued to use their PPI. Serum Mg(2+) levels served as the primary endpoint. RESULTS: Inulin significantly enhanced serum Mg(2+) levels from 0.60 to 0.68 mmol/L in PPI-induced hypomagnesaemia patients, and from 0.84 to 0.93 mmol/L in controls. As a consequence 24 h urinary Mg(2+) excretion was significantly increased in patients with PPI-induced hypomagnesaemia (0.3-2.2 mmol/day). Symptoms related to hypomagnesaemia, including muscle cramps and paraesthesia, were reduced during intervention with inulin. CONCLUSION: Inulin increases serum Mg(2+) concentrations under PPI maintenance in patients with PPI-induced hypomagnesaemia.

The effect of a forced-air warming blanket on patients' end-tidal and transcutaneous carbon dioxide partial pressures during eye surgery under local anaesthesia: a single-blind, randomised controlled trial.

Surgical drapes used during eye surgery are impermeable to air and hence risk trapping air underneath them. We investigated the effect of a forced-air warming blanket on carbon dioxide accumulation under the drapes in patients undergoing eye surgery under local anaesthesia without sedation. Forty patients of ASA physical status 1 and 2 were randomly assigned to either the forced-air warmer (n = 20) or a control heated overblanket (n = 20). All patients were given 1 l.min(-1) oxygen. We measured transcutaneous and end-tidal carbon dioxide partial pressures, heart rate, arterial pressure, respiratory rate, temperature and oxygen saturation before and after draping, then every 5 min thereafter for 30 min. The mean (SD) transcutaneous carbon dioxide partial pressure in the forced-air warming group stayed constant after draping at 5.7 (0.2) kPa but rose to a maximum of 6.4 (0.4) kPa in the heated overblanket group (p = 0.0001 for the difference at time points 15 min and later). We conclude that forced-air warming reduces carbon dioxide accumulation under the drapes in patients undergoing eye surgery under local anaesthesia.

Clinical responses observed with imatinib or sorafenib in melanoma patients expressing mutations in KIT.

BACKGROUND: Mutations in KIT are more frequent in specific melanoma subtypes, and response to KIT inhibition is likely to depend on the identified mutation. METHODS: A total of 32 patients with metastatic acral or mucosal melanoma were screened for mutations in KIT exons 11, 13 and 17. RESULTS: KIT mutations were found in 38% of mucosal and in 6% of acral melanomas. Three patients were treated with imatinib and one with sorafenib. All four patients responded to treatment, but three have since progressed within the brain. CONCLUSION: The observed clinical responses support further investigation of KIT inhibitors in metastatic melanoma, selected according to KIT mutation status.

Neuroglycopenia and adrenergic responses to hypoglycaemia: insights from a local epidemic of serendipitous massive overdose of glibenclamide.

AIMS: Recently, an unlicensed aphrodisiac formulation originating from China known as 'Power 1 Walnut' penetrated the illicit markets of South East Asia including Singapore. Subsequent toxicological analyses revealed that each 'Power 1 Walnut' pill was illegally adulterated with two prescription drugs--sildenafil 1 mg (a PDE5 inhibitor) and glibenclamide 93-98 mg (a long-acting sulphonylurea). As the drug was peddled to numerous people, a local 'hypoglycaemia epidemic' ensued, of which a small cluster presented to our hospital with severe hypoglycaemia. The aim is to characterize the demographics, clinical and labouratory aspects and postulate mechanisms for the relatively atypical presentation. METHODS: A retrospective study of all the patients admitted between 13th January to 15th June 2008 with hypoglycaemia was done with acquisition of all relevant data after ethical approval from our DSRB. RESULTS: 15 patients (25-73 years old) presented with severe hypoglycaemia. All of them presented with neuroglycopenic symptoms (5-confusion, 6-drowsiness to loss of consciousness, 4-seizures and 1-coma) 12-36 h after ingestion of 'Power 1 Walnut'. Liquid chromatography-mass spectrometry (LC/MS) confirmed the presence of glibenclamide in the urine. None experienced a full-blown hypoglycaemia-associated autonomic response defined as sweating, sensation of warmth, anxiety, tremor, nausea, palpitations, tachycardia, and hunger. Only 4/16 patients had symptoms of a partial autonomic response, and 3/16 patients had tachycardia and/or hypertension. CONCLUSIONS: The above suggests an inappropriate autonomic and catecholamine response to severe hypoglycaemia in these cases of serendipitous glibenclamide overdose. Possible reasons for the blunted autonomic responses and apparent autonomic failure are reviewed.

Drug interactions in dermatological practice.

Systemic drugs are increasingly used in the treatment of dermatological diseases. Due to the high prevalence of polypharmacy, dermatologists are increasingly faced with the complex problem of drug interaction. Unlike adverse drug reactions, which are often unpredictable, drug interactions can be avoided. This article presents the significant drug interactions that are encountered in clinical practice, with the interactions categorized into those involving antimicrobials, immunosuppressants, antimalarials and colchicine, retinoids and psychiatric medications. There are few commonly used drugs that often cause drug interactions. These include ciclosporin, azole antifungal drugs, erythromycin, sulfonamides and rifampicin, and dermatologists should be alert whenever encountering them. A section on interactions of drugs with health supplements, herbs and food is also included, in view of the increasing use of alternative and complementary therapies in many parts of the world.

Comparison between use of neuromuscular blocking agent and placebo with the intubating laryngeal mask airway.

INTRODUCTION: The intubating laryngeal mask airway (ILMA) is a specially-designed airway device that can be used for endotracheal intubation without direct laryngoscopy. The advantage of this device is that it allows blind endotracheal intubation with a predictably high success rate. The use of neuromuscular blocking agents in facilitating the use of the ILMA has been investigated in the Western population with a quoted successful intubation rate of 88-96 percent. This randomised, double-blind study aimed to see if the use of neuromuscular blocking agent is necessary for successful intubations. METHODS: A total of 150 patients, rated categories 1 and 2 on the American Society of Anesthesiology Physical Status Classification System, were induced with propofol 2.5 mg/kg and fentanyl 2 microg/kg. After insertion of the ILMA, the patients received either saline or 0.6 mg/kg of rocuronium. After 90 seconds, tracheal intubation was attempted using the specially-designed silicon endotracheal tube. In addition to the success rate of intubation, the incidence of complications was also recorded. RESULTS: The success rate for tracheal intubation within three attempts was 93.3 percent for the saline group and 92.0 percent for the rocuronium group; this was statistically insignificant. The time to securing the airway was 11.5 seconds for the saline group, compared to 10.0 seconds in the rocuronium group, but this was statistically insignificant. The incidence of coughing during insertion of the endotracheal tube was 42.7 percent in the saline group as compared to 1.3 percent in the rocuronium group (p-value is less than 0.001). 12 percent of the patients in the saline group moved during intubation, while none was reported to move in the rocuronium group (p-value is 0.003). These results compared favourably with rates quoted in studies conducted on Western populations. CONCLUSION: The intubating laryngeal mask airway-assisted intubation yields a high success rate, which was similar between the paralysed and non-paralysed patients, with no statistical significance. However, the non-paralysed patients were prone to coughing and movements during intubation, requiring supplemental propofol.

Meta-analysis of holmium laser enucleation versus transurethral resection of the prostate for symptomatic prostatic obstruction.

BACKGROUND: Holmium laser enucleation (HoLEP) is an alternative to transurethral resection (TURP) of the prostate for symptomatic prostatic obstruction. METHODS: Randomized controlled trials comparing HoLEP and TURP were identified systematically using Medline, Embase and The Cochrane Library. Primary outcomes were peak urinary flow rate (Qmax), postvoid residual volume, symptom score and quality of life. Secondary outcomes were duration of operation, hospital stay, blood loss, catheterization time and adverse events. RESULTS: There was no statistically significant difference between HoLEP and TURP in terms of Qmax at 6 and 12 months' follow-up. HoLEP was associated with significantly less blood loss, a shorter catheterization time and a shorter hospital stay. TURP was associated with reduced operating time. The techniques were similar in terms of urethral stricture, stress incontinence, transfusion requirement and rate of reintervention. CONCLUSION: HoLEP and TURP provide a similar improvement in Qmax. HoLEP, however, has several advantages over TURP, despite requiring more operating time. It is at least as safe as TURP in terms of adverse events.

Cortical edema in moderate fluid percussion brain injury is attenuated by vagus nerve stimulation.

Development of cerebral edema (intracellular and/or extracellular water accumulation) following traumatic brain injury contributes to mortality and morbidity that accompanies brain injury. Chronic intermittent vagus nerve stimulation (VNS) initiated at either 2 h or 24 h (VNS: 30 s train of 0.5 mA, 20 Hz, biphasic pulses every 30 min) following traumatic brain injury enhances recovery of motor and cognitive function in rats in the weeks following brain injury; however, the mechanisms of facilitated recovery are unknown. The present study examines the effects of VNS on development of acute cerebral edema following unilateral fluid percussion brain injury (FPI) in rats, concomitant with assessment of their behavioral recovery. Two hours following FPI, VNS was initiated. Behavioral testing, using both beam walk and locomotor placing tasks, was conducted at 1 and 2 days following FPI. Edema was measured 48 h post-FPI by the customary method of region-specific brain weights before and after complete dehydration. Results of this study replicated that VNS initiated at 2 h after FPI: 1) effectively facilitated the recovery of vestibulomotor function at 2 days after FPI assessed by beam walk performance (P<0.01); and 2) tended to improve locomotor placing performance at the same time point (P=0.18). Most interestingly, results of this study showed that development of edema within the cerebral cortex ipsilateral to FPI was significantly attenuated at 48 h in FPI rats receiving VNS compared with non-VNS FPI rats (P<0.04). Finally, a correlation analysis between beam walk performance and cerebral edema following FPI revealed a significant inverse correlation between behavior performance and cerebral edema. Together, these results suggest that VNS facilitation of motor recovery following experimental brain injury in rats is associated with VNS-mediated attenuation of cerebral edema.

Topical corticosteroid inhibits interleukin-4, -5 and -13 in nasal secretions following allergen challenge.

BACKGROUND: Cytokines and chemokines produced by allergen-reactive T-helper type 2 (Th2) cells may be pivotal to the pathophysiology of allergic disorders. OBJECTIVE: This study was performed to assess the effect of 7 days of topical corticosteroid on nasal allergen challenge (NAC) in terms of eosinophils, cytokines and chemokines obtained by nasal lavage and filter paper methods. METHODS: Patients with grass pollen seasonal-allergic rhinitis (n = 13) out of season received nasal challenge following matched placebo (twice daily into each nostril for 7 days) and fluticasone propionate (100 microg twice daily into each nostril for 7 days). Chemokine and cytokine levels were analysed using a sensitive automated bead immunoassay system at intervals up to 8 h after NAC. RESULTS: Levels of cytokines and chemokines from filter paper were generally higher than from nasal lavage. Fluticasone propionate caused a reduction in symptoms, total leukocyte counts and eosinophils, and abrogation of IL-4, IL-5, IL-6 and IL-13 responses in the filter paper taken in the late phase (P < 0.05 for IL-4 and IL-13, P < 0.01 for IL-5 and IL-6). Levels of chemokines (eotaxin, RANTES, MCP-1, MIP-1alpha, IL-8 and IP-10) were also reduced in the late phase (P < 0.01 at 8 h). However, levels of IL-2, IL-3, IL-7, IL-12 (p40 and p70), -15, TNF-alpha, IFN-gamma and GM-CSF were not affected. CONCLUSION: Fluticasone propionate has selective inhibitory effects on Th2 cytokine synthesis following nasal challenge, while also decreasing release of chemokines, but not affecting levels of Th1 cytokines.

Array comparative genomic hybridisation analysis of boys with X linked hypopituitarism identifies a 3.9 Mb duplicated critical region at Xq27 containing SOX3.

INTRODUCTION: Array comparative genomic hybridisation (array CGH) is a powerful method that detects alteration of gene copy number with greater resolution and efficiency than traditional methods. However, its ability to detect disease causing duplications in constitutional genomic DNA has not been shown. We developed an array CGH assay for X linked hypopituitarism, which is associated with duplication of Xq26-q27. METHODS: We generated custom BAC/PAC arrays that spanned the 7.3 Mb critical region at Xq26.1-q27.3, and used them to search for duplications in three previously uncharacterised families with X linked hypopituitarism. RESULTS: Validation experiments clearly identified Xq26-q27 duplications that we had previously mapped by fluorescence in situ hybridisation. Array CGH analysis of novel XH families identified three different Xq26-q27 duplications, which together refine the critical region to a 3.9 Mb interval at Xq27.2-q27.3. Expression analysis of six orthologous mouse genes from this region revealed that the transcription factor Sox3 is expressed at 11.5 and 12.5 days after conception in the infundibulum of the developing pituitary and the presumptive hypothalamus. DISCUSSION: Array CGH is a robust and sensitive method for identifying X chromosome duplications. The existence of different, overlapping Xq duplications in five kindreds indicates that X linked hypopituitarism is caused by increased gene dosage. Interestingly, all X linked hypopituitarism duplications contain SOX3. As mutation of this gene in human beings and mice results in hypopituitarism, we hypothesise that increased dosage of Sox3 causes perturbation of pituitary and hypothalamic development and may be the causative mechanism for X linked hypopituitarism.

Hemifacial spasm in Singapore: clinical characteristics and patients ' perceptions.

INTRODUCTION: The aim of this study was to determine the clinical characteristics and patients ' perception of hemifacial spasm (HFS) in Singapore. MATERIALS AND METHODS: A clinical survey of 137 consecutive patients with HFS seen in our Botulinum Toxin Clinic over a 15-month period was undertaken. RESULTS: Forty-six men and 91 women were interviewed. Their mean age at onset of HFS was 48 years. The median disease duration was 60 months (range, 2 to 360 months). Left-sided spasm was common in 51.8 % of patients, and the orbicularis oculi was the first muscle to be affected in 86.1 % of them. The majority (65 %) had the spasm aggravated by stress and anxiety. In fact, 32 patients perceived stress and anxiety as a possible aetiology of HFS. Stroke was a main concern in 17 patients and 7 patients thought the spasm was a sign of demonic possession or a bad omen. The spasm embarrassed 75.2 % of the patients, rendered 65 % of them depressed, affected the vision in 60.6 % of them and compromised their work performance in 35.8 %. Overall, treatment was delayed by a median interval of 6 months from onset of symptoms (range, 0 to 132). More than half (53.3 %) tried traditional therapies (acupuncture or herbal medicine), while only 48.2 % had botulinum toxin as the initial treatment. All patients eventually received botulinum toxin injections and more than 90 % showed improvement at 1 month posttreatment. CONCLUSIONS: The clinical characteristics and patients ' perception of HFS in Singapore were presented. HFS affects patients both psychosocially and functionally. Effective treatment with botulinum toxin exists and should be provided early to the patients.