Origin of and therapeutic approach to cardiac syndrome X:Results of the proton pump inhibitor therapy for angina-like lingering pain trial (PITFALL trial)

AIM: To investigate the frequency of gastroen-terological diseases in the etiology and the efficacy of proton pump inhibitors (PPIs) in the treatment of cardiac syndrome X (CSX) as a subform of non-cardiac chest pain (NCCP). METHODS: We investigated 114 patients with CSX using symptom questionnaires. A subgroup of these patients were investigated regarding upper gastrointestinal disorders (GIs) and treated with PPI. Patients not willing to participate in investigation and treatment served as control group. RESULTS: Thirty-six patients denied any residual symptoms and were not further evaluated. After informed consent in 27 of the remaining 78 patients, we determined the prevalence of disorders of the upper GI tract and quantifi ed the effect of treatment with pantoprazole. We found a high prevalence of gastroenterological pathologies (26/27 patients, 97%)with gastritis, gastroesophageal reflux disease (GERD) and acid reflux as the most common associated disorders. If treated according to the study protocol, these patients showed a significant improvement in the symptom score. Patients treated by primary care physicians, not according to the study protocol had a minor response to treatment (n = 19, -43%), while patients not treated at all (n = 26) had no improvement of symptoms (-0%). CONCLUSION: Disorders of the upper GI tract are a frequent origin of CSX in a German population and can be treated with pantoprazole if given for a longer period.

Helicobacter pylori infection and susceptibility to cardiac syndrome X:A systematic review and meta-analysis

BACKGROUND Cardiac syndrome X(CSX)is characterized by persistent angina with normal coronary arteries.Several pathophysiologic mechanisms have been introduced,particularly Helicobacter pylori(H.pylori)infection.AIM To investigate the association between H.pylori infection and CSX.METHODS All studies related to H.pylori infection and CSX were evaluated by comprehensive searches of global databases such as ISI Web of Knowledge,PubMed,Scopus,EMBASE,and Google scholar.Statistical analyses of selected articles were evaluated based on the summary odds ratio(OR).Finally,heterogeneity and publication bias were estimated using the I2 statistic and Cochrane Q-test as well as Begg’s and Egger’s tests.RESULTS A total of 11 studies met our inclusion criteria and 1435 patients(63%female,and 37%male)were reviewed.A significant association was observed between female patients and this syndrome(P=0.02).Our results showed a positive association between infection with this pathogen and presence of CSX(OR:5.65;95%confidence interval[CI]:4.17-7.64;I2:82.20).However,no significant association was observed with cagA-positive H. pylori strains and this syndrome (OR: 0.97;0.56-1.70 with 95%CI). Given the heterogeneity and publication bias, the resultsneed to confirmed by further prospective investigation.CONCLUSIONBased on our results, H. pylori infection is associated with an increased risk ofCSX. This bacterium appears to play a major role in the pathogenesis of CXS byinducing persistent inflammation.

Tongxinluo Capsule(通心络胶囊)for Cardiac Syndrome X：A Systematic Review and Meta-Analysis

Objective： To evaluate the efficacy and safety of Tongxinluo Capsule（通心络胶囊, TXL） for patients with cardiac syndrome X（CSX）. Methods： Randomized controlled trials（RCTs） regarding TXL in the treatment of CSX were searched in Chinese Biomedicine Literature Database, China National Knowledge Infrastructure, Chinese Scientific Journal Database, Wanfang Database, Pub Med, EMBASE, Cochrane Central Register of Controlled Trial, websites of the Chinese and International Clinical Trial Registry platform up to June 30, 2015. The intervention was either TXL alone or TXL combined with conventional treatment, while the control intervention was conventional treatment with or without placebo. Data extraction, methodological quality assessment and data analyses were performed according to the Cochrane criteria. The primary outcome was a composite event of death, acute myocardial infarction（AMI）, angina requiring hospitalization, revascularization, and heart failure. The secondary outcome measures were angina symptom improvement, electrocardiograph（ECG） improvement, and serum endothelin-1（ET-1） level. The adverse events were also recorded. RevMan 5.3 software was applied for data analyses. Results： Twelve RCTs（696 patients） were included. Compared with conventional treatment, the addition of TXL to conventional treatment showed some benefits on relieving angina symptoms [risk ratio（RR）： 1.46, 95% confidence interval（CI）（1.25, 1.71）, P〈0.01], and improving ECG [RR： 1.45, 95% CI（1.21, 1.74）, P〈0.01]. The pooled result did not support a benefit of TXL on reducing the incidence of primary outcome [RR： 0.20, 95% CI（0.02, 1.61）, P=0.13]. In addition, TXL decreased serum ET-1 concentration of CSX patients [standardized mean number： –1.63, 95% CI（–2.29, –0.96）, P〈0.01]. No serious adverse events were reported. Conclusions： TXL documents potential benefits on attenuating angina symptoms, improving ECG and decreasing serum ET-1 level for CSX patients. However, more rigorous RCTs with high quality are needed to confirm its efficacy and safety.

Summary of 32 Patients with Cardiac Syndrome X Treated by TCM Therapy of Regulating Qi Relieving Chest Stuffiness and Promoting Blood Circulation

Objective： To evaluate the clinical effect of Liqi Kuanxiong Huoxue method （宽胸活血,LKH, traditional Chinese medicine, TCM therapeutic method for regulating qi, relieving chest stuffiness and promoting blood circulation） in treating patients with cardiac syndrome X （CSX）. Methods： The prospective, non-randomized controlled study was conducted on 51 selected patients with CSX, who were non-randomly assigned to 2 groups, the treated group treated with LKH in addition to the conventional treatment （32 patients）, and the control group treated with conventional treatment （19 patients） like nitrate, diltiazem hydrochloride, etc. The treatment course was 14 days. The changes of such symptoms as angina pectoris, TCM syndrome and indexes of treadmill exercise test before and after treatment were observed. Results： After treatment, such symptoms as chest pain and stuffy feeling and palpitation in the treated group were improved more than those in the control group （P〈0.05）; the total effective rate on angina pectoris and TCM syndrome in the treated group was better than that in the control group （P〈0.05）. The treadmill exercise test showed that the maximal metabolic equivalent （Max MET）, the time of angina onset and ST segment depression by 0.1 mV were obviously improved after treatment in both groups, but the improvement in the treated group was better than that in the control group respectively （P〈0.05）. Conclusion： The LKH method could reduce the frequency of angina attacks and improve the clinical condition of patients with CSX.

Identification of syndrome X using intravascular ultrasound imaging and Doppler flow mapping

Background The purpose of this study was to assess the morphological changes and physiological function of coronary arteries in patients presenting with chest pain but having normal coronary angiograms, using intravascular ultrasound imaging (IVUS) and intracoronary Doppler (ICD) flow measurements, in order to elucidate the mechanism of syndrome X. Methods A total of 126 patients [67 males, 59 females, mean age (53.1±13.0) years] who experienced chest pain but had normal coronary angiograms were included in this study. ICD flow measurements of the left anterior descending coronary artery (LAD) were performed using a Cardiometrics FloMap Ⅱ system. Coronary flow velocity reserve (CFVR) was defined as the ratio of the average peak velocity during hyperemia to that at baseline, induced by an intracoronary bolus injection of 18 μg adenosine. A 3.2F or 2.9F 30 MHz mechanical rotating ultrasound catheter (CVIS, Boston Scientific) or a 3.0F 20MHz electronic ultrasound catheter (Endosonics) was used for IVUS. Results The mean CFVR value of the LAD was 2.71±0.74. Reduction of CFVR (<3.0) was found in 82 of 126 (65.1%) patients. IVUS images of the LAD were available for 109 patients. Plaque formation was detected in 76/109 (69.7%) patients. Based on the presence or absence of plaque formation as well as the reduction or non-reduction of CFVR, patients were divided into four groups: Group Ⅰ (n=10), normal IVUS findings and normal CFVR; Group Ⅱ (n=23), normal IVUS findings with reduction in CFVR; Group Ⅲ (n=29), IVUS evidence of plaque formation but normal CFVR; and Group Ⅳ (n=47), IVUS evidence of plaque formation with reduction in CFVR. Conclusion This study shows the important clinical value of a combination of IVUS and ICD in diagnosing patients with angiographically normal coronary arteries. Only 10% of patients studied (Group Ⅰ) were found to be truly free of coronary disease, while 20% of patients (Group Ⅱ) would be diagnosed as suffering from syndrome X.

Therapeutic efficacy observation on auricular point sticking therapy for cardiac syndrome X in women

Objective:To observe the clinical effect of auricular point sticking therapy for cardiac syndrome X(CSX)in women.Methods:A total of 64 patients were randomized into two groups by the random number table,with 32 cases in each group.Patients in the control group received conventional treatment for angina,while patients in the treatment group received auricular point sticking therapy on the basis of conventional treatment.After 8 weeks of treatment,the levels of serum estradiol(E2),nitric oxide(NO)and endothelium-1(ET-1)were compared to evaluate the therapeutic effect.Results:After 8 weeks of treatment,the total effective rate and markedly effective rate in the treatment group were significantly higher than those in the control group,and the between-group comparisons showed statistical significance(both P<0.05).After treatment,the scores of chest pain and tightness in the control group dropped significantly,and the intra-group comparisons showed statistical significance(both P<0.05);the scores of chest pain and tightness,palpitations,weakness and shortness of breath in the treatment group dropped significantly,and the intra-group comparisons showed statistical significance(all P<0.05);there were significant inter-group differences in the scores of chest pain and tightness.After treatment,the intra-group comparisons of E2,NO and ET-1 contents in the control group showed no statistical significance(all P>0.05),while the E2,NO and ET-1 contents in the treatment group changed significantly after treatment and were significantly different from those in the control group(all P<0.05).Conclusion:Auricular point sticking on the basis of conventional treatment was effective for CSX in women,and is worth clinical application.

Contemporary Treatment of Western and Chinese Medicine for Cardiac Syndrome X

Clinical reports on cardiac syndrome X（CSX） have been increasing in recent years.In general, CSX does not increase the cardiovascular mortality,but it can affect the patient＇s quality of life（QOL） and increase the incidence rates of cardiovascular and cerebrovascular events.Although a variety of drugs and therapies have been utilized in the clinical treatment,the management of CSX still represents a major challenge due to its unclear pathogenesis.It is necessary to explore more effective treatment programs.Many attempts have been made on trials of the Chinese medicine（CM） treatment for CSX and proved that CM has a certain advantage in efficacy to improve clinical symptoms and QOL.CM may provide a new approach for the effective treatment of CSX.

Lithium chloride ameliorates learning and memory ability and inhibits glycogen synthase kinase-3 beta activity in a mouse model of fragile X syndrome

In the present study,Fmr1 knockout mice （KO mice） were used as the model for fragile X syndrome.The results of step-through and step-down tests demonstrated that Fmr1 KO mice had shorter latencies and more error counts,indicating a learning and memory disorder.After treatment with 30,60,90,120,or 200 mg/kg lithium chloride,the learning and memory abilities of the Fmr1 KO mice were significantly ameliorated,in particular,the 200 mg/kg lithium chloride treatment had the most significant effect.Western blot analysis showed that lithium chloride significantly enhanced the expression of phosphorylated glycogen synthase kinase 3 beta,an inactive form of glycogen synthase kinase 3 beta,in the cerebral cortex and hippocampus of the Fmr1 KO mice.These results indicated that lithium chloride improved learning and memory in the Fmr1 KO mice,possibly by inhibiting glycogen synthase kinase 3 beta activity.

A Rapid Screening and Diagnosis on Fragile X Syndrome by PCR

Polymerase chain reaction (PCR) technique combined with direct detection by silver staining on denaturing DNA sequencing gel was used to analyze the (CGG)n repeats within the FMR1 gene on 169 suspected patients with mental retardation and 33 kindreds of 6 fragile X families. The results showed that : (1) No PCR products were detected in 3 males in the suspected group. (2) In the fragile X family studies, the 5 male probands failed to show any PCR products. (3) Diplex PCR with the primers flanking the FRAXE locus was used to serve as an internal control for the 8 above mentioned males and only normal products of the FRAXE locus were detected, indicating that the possibility of false negative results of the FRAXA locus could be eliminated. These findings suggested that analysis of (CGG)n repeat within the FMR1 gene by PCR technique could efficiently detect premutation carriers and that negative PCR products in mentally retarded males might highly imply the diagnosis of fragile X syndrome after the false negative results have been excluded by diplex PCR. This PCR assay is suitable for the screening and diagnosis of fragile X syndrome in a large number of populations due to its rapidity, simplicity, stability and reliability.

Reducing histone acetylation rescues cognitive deficits in mouse model of fragile X syndrome

Fragile X syndrome(FXS)is the most prevalent inherited intellectual disability,resulting from a loss of fragile X mental retardation protein(FMRP).Patients with FXS suffer lifelong cognitive disabilities,but the function of FMRP in the adult brain and the mechanism underlying age-related cognitive decline in FXS is not fully understood.Here,we report that a loss of FMRP results in increased protein synthesis of histone acetyltransferase EP300 and ubiquitinationmediated degradation of histone deacetylase HDAC1 in adult hippocampal neural stem cells(NSCs).Consequently,FMRPdeficient NSCs exhibit elevated histone acetylation and age-related NSC depletion,leading to cognitive impairment in mature adult mice.Reducing histone acetylation rescues both neurogenesis and cognitive deficits in mature adult FMRPdeficient mice.Our work reveals a role for FMRP and histone acetylation in cognition and presents a potential novel ther⁃apeutic strategy for treating adult FXS patients.

Metabolic syndrome is directly associated with gamma glutamyl transpeptidase elevation in Japanese women

AIM:This study aimed to determine whether metabolic syndrome is directly or indirectly,through fatty liver,associated with elevated gamma-glutamyl transpeptidase (GGT) levels in Japanese women. METHODS:From 4 366 women who received their annual health check-up,4 211 women were selected for analysis. All 4 211 women were negative for both hepatitis B surface antigen and antibody to hepatitis C virus.Clinical and biochemical variables were examined by using univariate and multivariate analysis. RESULTS:A raised GGT level (>68 IU/L) was seen in 258 (6.1%) of the 4 211 women.In univariate analysis,all variables examined (age,body mass index,blood pressure, hemoglobin concentration,fasting blood glucose, glycosylated hemoglobin Alc,cholesterol,triglyceride,and uric acid) were associated with the elevated GGT level, whereas in multivariate analysis,four variables (age≧50 yr, hemoglobin≧14 g/dL,triglyceride≧150 mg/dL,and presence of diabetes) were significantly and independently associated with raised GGT level.Clinical variables predicting the presence of ultrasonographic evidence of fatty liver were also examined by multivariate analysis;four variables were associated with the presence of fatty liver:BMI≧25 kg/m^2, hemoglobin≧14 g/dL,triglyceride≧150 mg/dL,and uric acid ≧ 7 mg/dL.There was no significant association between the raised GGT level and the presence of fatty liver. Hypertriglyceridemia was significantly and independently associated with both the raised GGT level and the presence of fatty liver. CONCLUSION:Metabolic syndrome seemed to be directly, not indirectly through fatty liver,associated with the raised GGT level in Japanese women.

Expression changes of microtubule associated protein 1B in the brain of Fmr1 knockout mice

Objective To explore the regulatory effect of fragile X mental retardation protein （FMRP） on the translation of microtubule associated protein 1B （MAP1B）. Methods The expressions of MAP1B protein and MAP1B mRNA in the brains of 1-week and 6-week old fragile X mental retardation-1 （FmrI） knockout （KO） mice were investigated by immunohistochemistry, Western blot, and in situ hybridization, with the age-matched wild type mice （WT） as controls. Results The mean optical density （MOD） of MAP1B was significantly decreased in each brain region in KO6W compared with WT6W, whereas in KO1W, this decrease was only found in the hippocampus and cerebellum. MAP1B in 6-week mice was much less than that in 1-week mice of the same genotype. The results of Western blot and in situ hybridization showed that MAP1B protein and MAP1B mRNA were significantly decreased in the hippocampus of both KO1W and KO6W. Conclusion The decreased MAP1B protein and MAP1B mRNA in the Fmrl knockout mice indicate that FMRP may positively regulate the expression of MAP1B.

Effects of Chinese herbal medicine Yiqi Huaju Qingli Formula in metabolic syndrome patients with microalbuminuria:a randomized placebo-controlled trial

BACKGROUND： Microalbuminuria （MAU） is a key component of metabolic syndrome （MetS） and is an early sign of diabetic nephropathy as well. Although routine Western medicine treatments are given to MetS patients to control high blood pressure, hyperglycemia and dyslipidemia, some patients still experience progressive renal lesions and it is necessary to modify and improve the treatment strategy for MetS patients. OBJECTIVE： To investigate the efficacy of Yiqi Huaju Qingli Herb Formula, a compound traditional Chinese herbal medicine, in MetS patients with MAU when it is combined with routine Western medicine treatment. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS： Sixty patients with MetS were randomized into the Chinese herbal formula group （CHF, Yiqi Huaju Qingli formula treatment in combination with Western medicine） and control group （placebo in combination with Western medicine）. All treatments were administered for 12 weeks. MAIN OUTCOME MEASURES： Urinary microalbumin （MA）, urinary albumin-to-creatinine ratio （UACR）, 24-hour total urine protein （24-hTP）, body mass index （BMI）, waist circumference （WC）, waist-to-hip ratio （WHR）, fasting plasma glucose （FPG）, 2-hour postprandial plasma glucose （2-hPPG）, glycosylated hemoglobin （HbAlc）, homeostasis model assessment for insulin resistance （HOMA-IR）, blood lipid profile and blood pressure were observed. RESULTS： Compared with the control group, CHF treatment significantly decreased BMI （P〈0.05）, WC （P〈0.01） and WHR （P〈0.01）. Both groups had significant decreases in FPG, 2-hPPG, HbAlc, HOMA-IR, MA, and UACR, with CHF treatment showing better effects on these parameters compared with the control treatment （P〈0.05）. Both treatments significantly reduced the levels of total cholesterol, low-density lipoprotein cholesterol and triacylglycerol （TAG）, and a greater reduction in TAG was observed with CHF treatment （P〈0.05）. The level of high-density lipoprotein cholesterol did not change in the control group after treatment （P〉0.05）, whereas it significantly increased with CHF treatment （P〈0.01）. Compared with before the treatment, significant decreases in systolic blood pressure, diastolic blood pressure and mean arterial blood pressure were observed in both groups （P〈0.01）. However, there was no significant difference between the two groups （P〉0.05）. CONCLUSION： Combined treatment ofYiqi Huaju Qingli Formula and Western medicine significantly alleviated MAU, which may correlate with the improvement of insulin sensitivity and glucose and lipid metabolism. TRIAL REGISTRATION IDENTIFIER： This trial was registered in the Chinese Clinical Trial Registry with the identifier ChiCTR-TRC-11001633.

Metabolic syndrome after liver transplantation: Preventable illness or common consequence?

The metabolic syndrome is common after liver transplant being present in approximately half of recipients. It has been associated with adverse outcomes such as progression of hepatitis C and major vascular events. As the United States population ages and the rate of obesity increases, prevention of the metabolic syndrome in the post-transplant population deserves special consideration. Currently, the metabolic syndrome after transplant appears at least two times more common than observed rates in the general population. Specific guidelines for patients after transplant does not exist, therefore prevention rests upon knowledge of risk factors and the presence of modifiable elements. The current article will focus on risk factors for the development of the metabolic syndrome after transplant, will highlight potentially modifiable factors and propose potential areas for intervention. As in the non-transplant population, behavioral choices might have a major role. Opportunities exist in this regard for health prevention studies incorporating lifestyle changes. Other factors such as the need for immunosuppression, and the changing characteristics of wait listed patients are not modifiable, but are important to know in order to identify persons at higher risk. Although immunosuppression after transplant is unavoidable, the contribution of different agents to the development of components of the metabolic syndrome is also discussed. Ultimately, an increased risk of the metabolic syndrome after transplant is likely unavoidable, however, there are many opportunities to reduce the prevalence.

Enhancing the treatment of metabolic syndrome with integrative medicine

Metabolic syndrome, with the main clinical manifestations of obesity, dyslipidemia, elevated blood pressure, and elevated blood glucose levels, has become an increasingly prevalant global public health concern. Metabolic syndrome is a convergence of multiple risk factors related to cardiovascular disease. When the concept of metabolic syndrome was initially proposed, some researchers thought the concept was unnecessary, since there were already measures in place to describe the separate cardiovascular risk factors such as dyslipidemia, hypertension and diabetes. However, a large number of epidemiological investigations confirmed that even if blood glucose or blood pressure did not reach the cutoff point of the diseases,

Developmental Impairments of Synaptic Refinement in the Thalamus of a Mouse Model of Fragile X Syndrome

While somatosensory over-reactivity is a common feature of autism spectrum disorders such as fragile X syndrome(FXS),the thalamic mechanisms underlying this remain unclear.Here,we found that the developmental elimination of synapses formed between the principal nucleus of V(PrV)and the ventral posterior medial nucleus(VPm)of the somatosensory system was delayed in fragile X mental retardation 1 gene knockout(Fmr1 KO)mice,while the developmental strengthening of these synapses was disrupted.Immunohistochemistry showed excessive VGluT2 puncta in mutants at P12–13,but not at P7–8 or P15–16,confirming a delay in somatic pruning of PrV-VPm synapses.Impaired synaptic function was associated with a reduction in the frequency of quantal AMPA events,as well as developmental deficits in presynaptic vesicle size and density.Our results uncovered the developmental impairment of thalamic relay synapses in Fmr1 KO mice and suggest that a thalamic contribution to the somatosensory over-reactivity in FXS should be considered.

Negative Association of Domestic Activity and Active Commuting with Metabolic Syndrome in a Chinese Population Aged 35-64 Years

Objective To understand the associations of physical activity domains with metabolic syndrome among a middle-aged Chinese population. Methods In all, 3326 professional adults aged 35-64 years from Beijing and Zhejiang province were recruited with a cluster random sampling method. The Global Physical Activity Questionnaire was modified, and the recommended Asia-Pacific cut-offs of waist circumstance were introduced into the criteria for metabolic syndrome from the Adult Treatment Panel III. A binary logistic regression model was applied to examine the association of all physical activity domains with the risk of the syndrome. Results Participants who engaged in domestic activity for 〉1176 MET-min/week had a 41.6% less chance of having metabolic syndrome [odds ratio （OR）, 0.584; 95% confidence interval （CI）, 0.480-0.710] than those without this activity. In adjusted models, adults who actively commuted for 〉33 MET-rain/week but 〈52g MET-min/week had a 25% less chance of having the syndrome （OR, 0.750; 95% CI, 0.582-0.966） than those who did not. No interaction was detected between the two domains of activity and the syndrome. Conclusion This study highlighted the independently negative association of traffic and house activity with the prevalence of the syndrome in this sample with a generally low level of moderate activity.

Metabolic Syndrome: Consensus and Controversy: State of the Art

Metabolic syndrome is an epidemic that affects more and more people, increasing the probability of suffering metabolic and cardiovascular diseases in the short, medium or long term depending on the severity. The purpose of this article is to review the metabolic syndrome, assessing consensus, controversy and prevalence. The methodology was the preparation of a literature review on various health care databases, which were from 43 articles published from 2010 to 2015, in the general population. SM rate ranges from 0% to 90% depending on genders, ages and regions. There is still lack of consensus on cutoffs of diagnostic criteria. Thus, it is concluded that the prevalence of metabolic syndrome is being increased, urging the need for early diagnosis and treatment to promote the health of the global population.

Axonal mRNA localization and local translation in neurodegenerative diseases

The regulation of mRNA localization and local translation play vital roles in the maintenance of cellular structure and function.Many human neurodegenerative diseases,such as fragile X syndrome,amyotrophic lateral sclerosis,Alzheimer’s disease,and spinal muscular atrophy,have been characterized by pathological changes in neuronal axons,including abnormal mRNA translation,the loss of protein expression,or abnormal axon transport.Moreover,the same protein and mRNA molecules have been associated with variable functions in different diseases due to differences in their interaction networks.In this review,we briefly examine fragile X syndrome,amyotrophic lateral sclerosis,Alzheimer’s disease,and spinal muscular atrophy,with a focus on disease pathogenesis with regard to local mRNA translation and axon transport,suggesting possible treatment directions.

Erectile dysfunction in Fragile X patients

Aim:To study a possible defect in spermatogenesis of Fragile X syndrome(FXS)patients.Methods:Two different polymerase chain reaction(PCR)based methods were used for the molecular diagnosis of FXS.Sperm collection was done mostly according to the laboratory manual of the World Health Organization.Results:We failed to collect sperm samples from five Fragile X subjects aged 18-60 years as a result of an unexpected erectile dysfunction(ED). Multiple examinations of the same subject at different times,and of different subjects from different provinces by different physicians,showed the same result consistently in all five subjects examined.Conclusion:Erectile reflex is an instinctive response in all healthy males.The absence of erection can be caused by hormonal,physical or neuronal malfunction.As hormonal profiles were reported to be generally normal in Fragile X men,we propose that an unknown physical factor or the neuronal circuit,or both,underlying the erection is compromised.The finding of ED in Fragile X patients may help better understand the clinical spectrum and pathogenesis of the disease.(Asian J Androl 2006 Jul;8:483-487)