Early cardiovascular remodelling in Fabry disease

Aims

Fabry disease (FD) is a rare X-linked genetic disorder caused by the deficiency or absent activity of lysosomal α-galactosidase A. Cardiovascular remodelling is a hallmark of FD. The present study aimed to comprehensively evaluate the cardiac, vascular and microvascular status in a population of patients with genetic mutations for FD without left ventricular hypertrophy (LVH).

Methods and results

This study includes subjects carrying genetic mutations for FD (Fabry disease mutation-carrier, FDMC) without LVH (n?=?19). A group of control subjects (n?=?19) matched for age, sex, body mass index and cardiovascular risk factors were also included. All subjects underwent echocardiography, carotid ultrasound scan, endothelial flow-mediated dilatation (FMD) and nailfold capillaroscopy (NFC) assessment. When compared to the subjects in the control group, FDMC patients showed significantly lower mean values of systolic myocardial velocity (7.33?±?1.28 vs. 10.08?±?1.63 cm/s, p?<?0.0001), longitudinal systolic strain (?18.07?±?1.72 vs. ?21.15?±?2.22 %, p?<?0.0001), significantly higher E/E’ mean values (7.15?±?1.54 vs. 5.98?±?1.27, p?=?0.016) and intima-media thickness mean values (0.80?±?0.20 vs. 0.61?±?0.19 mm, p?=?0.005), significantly lower FMD (8.3?±?4.6 vs. 12.2?±?5.0 %, p?=?0.02), more atypical capillaries and irregular NFC architecture in FDMC than control subjects (52.6 vs. 0 %, p?<?0.0001; 78.9 vs. 36.8 %, p?=?0.02 respectively).

Conclusions

FD progressively involves cardiac, macrovascular and microvascular systems in an early stage. These features are present even in asymptomatic mutation carriers without LVH.     

Uncertain diagnosis of Fabry disease: Consensus recommendation on diagnosis in adults with left ventricular hypertrophy and genetic variants of unknown significance

Background

Screening in subjects with left ventricular hypertrophy (LVH) reveals a high prevalence of Fabry disease (FD). Often, a diagnosis is uncertain because characteristic clinical features are absent and genetic variants of unknown significance (GVUS) in the α-galactosidase A (GLA) gene are identified. This carries a risk of misdiagnosis, inappropriate counselling and extremely expensive treatment. We developed a diagnostic algorithm for adults with LVH (maximal wall thickness (MWT) of > 12 mm), GLA GVUS and an uncertain diagnosis of FD.

Methods

A Delphi method was used to reach a consensus between FD experts. We performed a systematic review selecting criteria on electrocardiogram, MRI and echocardiography to confirm or exclude FD. Criteria for a definite or uncertain diagnosis and a gold standard were defined.

Results

A definite diagnosis of FD was defined as follows: a GLA mutation with ≤ 5% GLA activity (leucocytes, mean of reference value, males only) with ≥ 1 characteristic FD symptom or sign (neuropathic pain, cornea verticillata, angiokeratoma) or increased plasma (lyso)Gb3 (classical male range) or family members with definite FD. Subjects with LVH failing these criteria have a GVUS and an uncertain diagnosis. The gold standard was defined as characteristic storage in an endomyocardial biopsy on electron microscopy. Abnormally low voltages on ECG and severe LVH (MWT > 15 mm) < 20 years exclude FD. Other criteria were rejected due to insufficient evidence.

Conclusions

In adults with unexplained LVH and a GLA GVUS, severe LVH at young age and low voltages on ECG exclude FD. If absent, an endomyocardial biopsy with electron microscopy should be performed.     

Hearing loss in children with Fabry disease

Background

Hearing loss (HL) is a well-known feature of Fabry disease (FD). Its presence and characteristics have mainly been studied in adult patients, while only limited data are available on the presence and degree of HL in children with FD. This prompted us to study hearing sensitivity in pediatric FD patients.

Methods

All available audiograms of the Dutch and Norwegian children with FD were retrospectively collected. First, hearing sensitivity was determined by studying hearing thresholds at low, high, and ultra-high frequencies in children with FD and comparing them to zero dB HL, i.e., healthy children. In addition, the presence and type of slight/mild HL (defined as hearing thresholds at low frequencies of 25–40 dB HL) and moderate to severe HL (hearing thresholds >40 dB HL) at first visit were analyzed. If available, follow-up data were used to estimate the natural course of hearing sensitivity and HL in children with FD.

Results

One-hundred-thirteen audiograms of 47 children with FD (20 boys, median age at first audiogram 12.0 (range 5.1–18.0) years) were analyzed. At baseline, slight/mild or moderate to severe HL was present in three children (6.4%, 2 boys). Follow-up measurements showed that three additional children developed HL before the age of 18. Of these six children, five had sensorineural HL, most likely caused by FD. Compared to healthy children (zero dB HL), FD children showed increased hearing thresholds at all frequencies (p < 0.01), which was most prominent at ultra-high frequencies (>8 kHz). Hearing sensitivity at these ultra-high frequencies deteriorated in a period of 5 years of follow-up.

Conclusion

A minority of children with FD show slight/mild or moderate to severe HL, but their hearing thresholds are poorer than the reference values for normal-hearing children. Clinical trials in FD children should demonstrate whether HL can be prevented or reversed by early treatment and should specifically study ultra-high frequencies.

     

Natural course of Fabry disease and the effectiveness of enzyme replacement therapy: a systematic review and meta-analysis

Objective

Current available evidence on long-term effectiveness of enzyme replacement therapy (ERT) for Fabry disease is limited. More insight is needed whether ERT effectiveness differs in patients with and without baseline end-organ damage.

Design

Through a systematic review, untreated and ERT treated males and females with Fabry disease were compared for main clinical outcomes: renal function, left ventricular mass (LVmass), cerebral white matter lesions (WMLs) and end-organ complications. Through a meta-analysis ERT effectiveness was estimated in different disease stages.

Data extraction

Two reviewers assessed quality of the included studies according to guidelines for prognosis research. Data were synthesized using a random effects meta-analysis.

Results

Thirty-one studies were systematically reviewed while six studies were included in the meta-analysis. In patients with a GFR?>?60 ml/min/1.73 m², decline of renal function was similar for treated and untreated patients. Only ERT treated males with a GFR?<?60 ml/min/1.73 m² had a slower rate of decline in renal function, possibly attributable to anti-proteinuric therapy. Regardless of left ventricular hypertrophy (LVH) at baseline, LVmass remained stable or increased in males despite ERT, however at a slower rate compared to untreated male patients. In ERT treated females with LVH LVmass decreased, and remained stable in females without LVH. WMLs can not be prevented by ERT. Stroke, cardiac and end-stage renal complications develop, though the incidence of new complications seems to be reduced during ERT.

Conclusion

ERT is effective in reducing LVH, but has a limited effect on renal function. Improved treatment options are needed for Fabry disease.     

Cognitive dysfunction and depression in Fabry disease: a systematic review

Background

Fabry disease, an X-linked lysosomal storage disorder, leads to multi-organ dysfunction, including cerebrovascular disease and psychological disorders. However, the prevalence and pattern of associated cognitive dysfunction is not well understood.

Objectives

To investigate whether there is reliable evidence for neuropsychological impairment in patients with Fabry disease and which cognitive domains are affected. To estimate the prevalence of and factors associated with depression in patients with Fabry disease.

Method

Qualitative systematic review of the literature of studies conducting neuropsychological assessment or measuring the prevalence of depression in adults with Fabry disease using the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines where appropriate.

Results

There is some evidence for neuropsychological impairment in Fabry disease in executive functioning, information processing speed and attention, with preservation of: general intellectual functioning, memory, naming, perceptual functioning and global cognitive functioning. Prevalence rates of depression in Fabry disease ranged from 15 % to 62 %, with the largest study to date reporting a prevalence rate of 46 %. The most common factor associated with depression was neuropathic pain, both directly and indirectly by affecting social and adaptive functioning.

Conclusion

Our review suggests that Fabry disease may be associated with a characteristic pattern of cognitive deficits and a high prevalence of psychological disorders such as depression but highlights the limited available data. Exploring the nature of cognitive impairment in Fabry disease using standardised neuropsychological assessment, brain imaging and measures of depression is an important task for future research.     

Prevalence of Fabry disease in a predominantly hypertensive population with left ventricular hypertrophy

Background

Patients with Fabry disease (FD) develop progressive left ventricular hypertrophy (LVH). In screening studies in patients with LVH, the prevalence of FD ranges from 0 to 12%. This variability is attributable to different factors like diverging inclusion and exclusion criteria, the evaluation of selected populations and suboptimal screening methods.In this study, we aimed to determine the prevalence of FD in an unselected population of everyday clinical practice presenting LVH, defined as a maximal end-diastolic septal or posterior wall thickness ≥ 13 mm, without exclusion of patients with arterial hypertension or valvular pathology, and using optimal screening methods.

Methods

In adult males, a two-tier approach was used; α-Galactosidase A (aGAL A) activity was measured using a dried bloodspot test (DBS) and diagnosis was confirmed by mutation analysis of the GLA gene. In females, mutation analysis was the primary screening tool.

Results

362 men and 178 women were screened. Six patients were diagnosed with a genetic sequence alteration of the GLA gene. One man had a novel mutation, GLA p.Ala5Glu (c.44C > A), presenting as classical FD. Another man and three women had the previously described GLA p.Ala143Thr (c.427G > A) mutation, which generally presents as an attenuated phenotype. One woman had a novel sequence alteration c.639 + 6A > C, which appeared to be a polymorphism. All true Fabry patients had arterial hypertension (AHT), and one had hypertrophic obstructive cardiomyopathy (HOCM).

Conclusions

In a group of unselected patients with LVH, we found a prevalence of Fabry disease of 0.9%. AHT or type of hypertrophy should not be an exclusion criterion for screening for FD.     

Fractal Analysis of Contrast-Enhanced CT Images to Predict Survival of Patients with Hepatocellular Carcinoma Treated with Sunitinib

Background

Intratumoral heterogeneity is a well-recognized feature of malignancy.

Aims

To assess the heterogeneity of tumor using fractal analysis of contrast-enhanced computed tomography (CE-CT) images for predicting survival of hepatocellular carcinoma (HCC) patients treated with sunitinib.

Methods

The patient cohort comprised 23 patients (19 men, 4 women; mean age 61.5 years) with HCC who underwent CE-CT at baseline and after one cycle of sunitinib. Arterial-phase (AP) and portal-phase (PP) CE-CT images were analyzed using a plugin software for ImageJ (NIH, Bethesda, MD). A differential box-counting method was employed to calculate the fractal dimension (FD) of the tumor. Tumor FD, density, and size were compared with survival.

Results

Median progression-free survival (PFS) was 4.43 months. Patients were grouped into a favorable PFS (PFS >4.43 months; 9 patients) and an unfavorable PFS group (PFS ≤4.43; 13 patients). The baseline FD on both the AP and PP images was lower in the favorable PFS group than in the unfavorable PFS group (both P = 0.03). There was a significant difference in the change of the FD on the AP image between the favorable and unfavorable PFS groups (P = 0.02). Tumor density and size showed no significant correlations with PFS. In the Kaplan–Meier analysis, patients with tumors showing lower FD on the AP image at baseline showed longer PFS (P = 0.002). Patients with tumors showing a greater reduction in the FD on the PP image after one cycle of the therapy showed longer overall survival (P = 0.002).

Conclusion

The FD of the tumor on CE-CT images may be a useful biomarker for HCC patients treated with sunitinib.     

Prevalence and Predictive Factors for Gastrointestinal Pathology in Young Men Evaluated for Iron Deficiency Anemia

Background

The prevalence of gastrointestinal lesions in young men with iron deficiency anemia (IDA) is unknown, and there are no evidence-based recommendations for the evaluation of the gastrointestinal tract in this population.

Aims

The purpose of this study was to assess the prevalence of significant GI lesions among young males with IDA, and to shed light on potential predictors of their presence.

Methods

Clinical, endoscopic, and histological data was retrospectively collected from medical records of 347 young males with IDA.

Results

Clinically significant GI lesions were diagnosed in 62 %. Upper GI lesions were found in 35 %. Peptic disease was the most common finding, diagnosed in 30 %. Celiac disease was diagnosed in 4 %. Lower GI tract lesions were diagnosed in 34 %. The most common findings were hemorrhoids (17 %) and inflammatory bowel disease (16 %). Malignant lesions were not detected. GI lesions were encountered more frequently when respective symptoms were obtained. Multivariate analysis showed that the presence of GI symptoms and the use of proton pump inhibitors were associated with an increased likelihood of significant GI lesions.

Conclusions

GI lesions are common among young men with IDA. GI evaluation is mandatory in symptomatic men and in asymptomatic men when the anemia is resistant to iron therapy. Symptoms may dictate the order of evaluation.     

Increasing prevalence of diabetes mellitus in association with fatty liver in a Japanese population

Background

The prevalence of diabetes mellitus (DM) has been increasing. The present study was carried out to examine the relationship between this increase and fatty liver.

Methods

Japanese participants who underwent regular health examinations in 1991, 1996, 2001, 2006, and 2011 were enrolled. Fatty liver was diagnosed using ultrasonography. DM was defined as requiring the use of medication for DM, having a fasting blood glucose level ≥126 mg/dl, or hemoglobin A1c level ≥6.5 %.

Results

Logistic regression analysis on data from 11,235 participants (6,882 men and 4,271 women) in 2011 revealed that the association between fatty liver and DM was independent of age, body composition, and other confounders [odds ratio (OR) 1.97, 95 % confidence interval (95 % CI) 1.66–2.32 in men, and OR, 3.12; 95 % CI, 2.29–4.26 in women]. In 2006, 5,318 participants did not have DM and were able to be followed up in 2011. Fatty liver in 2006 was an independent predictor of DM in 2011 [OR 1.73 (95 % CI 1.20–2.50) in men, 4.13 (2.16–8.10) in women]. The prevalence of DM increased significantly during the 20-year period examined among both men (6.0, 8.9, 10.0, 10.8, 12.0 %, P < 0.001) and women (3.3, 4.5, 4.2, 4.1, 5.1 %, P = 0.004), accompanied with an increased prevalence of fatty liver among both men (10.8, 26.3, 33.8, 36.7, and 38.0 %, P < 0.001) and women (6.5, 16.7, 22.2, 21.3, and 20.8 %, P < 0.001).

Conclusion

Fatty liver independently predicts both present and future DM. Fatty liver may play an important role in the recent increases in the prevalence of DM.     

Association of Genetic Variants in GNβ3 with Functional Dyspepsia: A Meta-Analysis

Background

Functional dyspepsia (FD) is a functional upper gastrointestinal disorder. The etiology and pathogenesis of FD remain unclear, with genetic factors playing an important role. Previous studies investigated the association of C825T in GNβ3 with FD, with conflicting results reported.

Aims

The aim of this meta-analysis is to assess the association of genetic variants in GNβ3 with FD.

Methods

We performed a systematic literature search in PubMed, Cochrane Library, Google Scholar, and Web of Knowledge, and conducted a meta-analysis to assess the association of C825T in GNβ3 with FD. For sensitivity analysis, we analyzed the association between C825T and subtypes of FD. We also performed meta-analyses separately for individual ethnic groups/countries of origin.

Results

A total of eight studies met the eligibility criteria and were included in our analyses. Our meta-analysis finds no association between 825CC and FD (OR 1.19, 95 % CI 0.84–1.67, p = 0.328). However, the association is significant under an additive model (OR 0.59, 95 % CI 0.38–0.92, p = 0.018). Sensitivity analysis indicated a significant association of C825T with FD in participants from Korea but not in those from Japan, Europe, or the United States. We also detected a significant association of this SNP with dysmotility.

Conclusions

The genetic variant C825T in GNβ3 is significantly associated with FD under an additive model and the association is race-specific. Further studies with larger samples sizes are needed to validate our findings and to explore the potential mechanism underlying the association.     

Metabolic syndrome in central Brazil: prevalence and correlates in the adult population

Background

The prevalence of metabolic syndrome (MetS) has increased in developing countries in recent decades. This syndrome, a clustering of metabolic abnormalities, has been correlated to various socioeconomic and behavioral variables. We investigated the prevalence and prevalence ratios (PR) of MetS and related factors in an adult population of the Federal District (FD) of Brazil, which is located in the central region of the country.

Methods

A cross-sectional, population-based study conducted in 2007, with 2130 adults (aged 18?years or older) in the FD of Brazil. Metabolic syndrome was defined according to the recently harmonized criteria. The prevalence of MetS and PR were estimated for each sex according to the diagnostic components and the overall contribution of the selected correlates.

Results

The overall prevalence of MetS was 32.0% (95%CI: 28.9?C35.2), with no gender difference. The single component with the greatest contribution to the diagnosis of MetS was hypertension in men (PR 5.10, 95%CI: 3.17?C8.22) and high waist circumference in women (PR 5.02, 95%CI: 3.77?C6.69). The prevalence of MetS increased significantly and progressively with age and excess weight. In women, higher education was protective against MetS (PR 0.66, 95%CI: 0.49?C0.89) compared to 8 or less years of education. There was no association between the prevalence of MetS and behavioral variables studied.

Conclusions

This study provides comprehensive and alarming data about the prevalence of MetS among the adult population of Brazil??s FD. The results suggest that reducing education inequalities may be an important public policy goal to improve health outcomes, especially among women.     

Nitric Oxide Synthase Gene Polymorphisms in Functional Dyspepsia

Objective

Nitrinergic control is important in meal-induced satiety. The aim of this study was to assess functional polymorphisms in nitric oxide synthase (NOS) genes in the susceptibility to functional dyspepsia (FD).

Methods

Genomic DNA from 89 patients with FD and 180 healthy subjects matched for age and gender were typed for the gene of neuronal NOS (nNOS, rs2682826), inducible NOS (iNOS, rs2297518) and a variable number tandem repeat in intron 4 of endothelial NOS (eNOS). Patients ingested 500 mL of Ensure^® during a 20 min period and dyspeptic symptoms were scored.

Results

Genotype frequencies of eNOS and iNOS were not significantly different between FD patients and controls. The frequency of the T allele in nNOS was significantly higher in FD patients compared to the controls (49 vs. 16 %; odds ratio 5.01; 95 % confidence interval 2.83–9.01; p < 0.05). Patients with the T allele in the nNOS polymorphism reported a higher satiation score than those with the CC genotype during the nutrition drink test (median 179 vs. 117; p < 0.05).

Conclusion

The nNOS gene polymorphism is associated with susceptibility to FD and influences satiation in FD patients. Our data support the importance of NOS gene polymorphisms in the pathogenesis of FD.     

Sexual Violence and Mental Health Symptoms Among National Guard and Reserve Soldiers

BACKGROUND

Reserve and National Guard (NG) soldiers report disproportionate mental health problems relative to active duty military upon returning from the Iraq and Afghanistan conflicts. However, few studies have examined whether exposure to particular types of traumatic events (e.g., lifetime sexual violence) is associated with this increased burden of psychopathology.

OBJECTIVE

The current study examined the prevalence of lifetime sexual violence exposure as well as the adjusted odds and population attributable fraction of psychopathology associated with sexual violence in a large sample of male and female Reserve and NG soldiers.

DESIGN

Baseline structured telephone interviews were conducted in 2009.

PARTICIPANTS

1,030 Reserve (23 % female) and 973 NG (15 % female) soldiers.

MAIN MEASURES

Four items assessed lifetime and deployment-related sexual violence. Probable lifetime and past-year posttraumatic stress disorder (PTSD) and depression were assessed with the PTSD Checklist and the Patient Health Questionnaire, respectively.

KEY RESULTS

Lifetime sexual violence prevalence was 37.4 % and 27.6 % among Reserve and NG women, and 4.3 % and 3.7 % among Reserve and NG men, respectively. Recent deployment-related sexual violence ranged from 1.4 to 2.6 % for women and 0 % for men. Regression analyses indicated that the adjusted odds of probable past-year and lifetime PTSD and depression were 1.2 to 3.5 times greater among those reporting sexual violence relative to non-victims. The proportion of probable lifetime PTSD and depression attributable to sexual violence was 45.2 % and 16.6 %, respectively, in the Reserves, and 10.3 % and 6.2 %, respectively, in the NG.

CONCLUSIONS

Lifetime sexual violence prevalence was high among female soldiers, with approximately one-third of Reserve and National Guard women reporting a history. The majority of sexual violence was not related to the most recent deployment; however, sexual violence contributed to a high burden of psychopathology. Findings emphasize a need to screen for lifetime sexual violence and associated mental disorders in military samples.     

Oral contraceptive pill use is associated with reduced odds of nonalcoholic fatty liver disease in menstruating women: results from NHANES III

Background

Higher prevalence of nonalcoholic fatty liver disease (NAFLD) in men and postmenopausal women than in premenopausal women has suggested a potential role of sex hormones in the pathogenesis of the disease. We sought to evaluate the association between oral contraceptive pills (OCP) and NAFLD and to determine whether adiposity mediates any effect.

Methods

We included 4338 women aged 20–60 years who were enrolled in the Third National Health and Nutrition Examination Survey from 1988 to 1994 in a population-based cross-sectional study. We defined NAFLD as moderate–severe steatosis on ultrasonography in women without excessive alcohol use or other identifiable causes. OCP use was based on self-report and was categorized as never, former or current use.

Results

The overall weighted prevalence of NAFLD was 11.6 % but lower in current (6.7 %) than in former (12.0 %) or never users (15.6 %, P = 0.016). In the multivariable model, current OCP users experienced a 50 % lower odds of NAFLD than never users (adjusted odds ratio 0.50; 95 % confidence interval 0.26, 0.98) after adjusting for age, race/ethnicity, smoking status, history of diabetes or hypertension and education. Further adjustment for body mass index or waist circumference significantly attenuated the OCP–NAFLD relationship.

Conclusions

In this large US-representative population, OCP use was associated with reduced odds of NAFLD. However, this association could be mediated or confounded by adiposity. Prospective studies are needed to further clarify the causal role of sex hormone.     

Chlamydia trachomatis prevalence, genotype distribution and identification of the new Swedish variant in Southern Germany

Purpose

In Germany, reliable data about the prevalence of urogenital Chlamydia trachomatis infections, causative genotypes, as well as corresponding clinical, demographic and behavioural information are sparse. We, therefore, performed a prospective prevalence study including 1,003 sexually active volunteers of a Southern German city.

Methods

Study participants completed a standardised questionnaire and provided first void urine samples for analysis. Our screening strategy included the performance of two nucleic acid amplification tests with different target genes, enabling the detection of the new Swedish variant of C. trachomatis (nvCT). Direct genotyping of positive specimens was performed by sequence analysis of the ompA gene.

Results and Conclusion

The overall prevalence of C. trachomatis infection was 4.2 % in women and 4.6 % in men. A relatively high prevalence of 8.3 % was found in men older than 25 years. Never using condoms was an independent risk factor for infection. The most common symptom was discharge; however, 64.5 % of infected females and all of the infected men were asymptomatic, supporting the need for screening programmes. The most frequently encountered genotypes were E (46.5 %), F (20.9 %) and K (14.0 %). Since the nvCT was detected in one female student, this is one of the rare studies that reports on the molecular identification of nvCT apart from Sweden.     

Prevalence of irritable bowel syndrome and functional dyspepsia,overlapping symptoms,and associated factors in a general population of Bangladesh

Background

This community-based survey aimed to find out the prevalence of irritable bowel syndrome (IBS), functional dyspepsia (FD), overlapping symptoms, and associated factors for overlap.

Method

By cluster sampling method, 3,000 (1,523 male) randomly selected adult subjects in the Sylhet district of Bangladesh were interviewed by a questionnaire based on ROME III criteria. Multivariate logistic regression analyses were done to find out the factors for overlap with significance level set at ≤0.05.

Results

The mean age of the study population was 33.9?±?16.4 years. Prevalence of IBS and FD and IBS-FD were 12.9 % (n?=?387), 8.3 % (n?=?249), and 3.5 % (n?=?105), respectively. Approximately 27.1 % of IBS patients and 42.1 % of FD patients had overlapping IBS-FD. The odds ratio for IBS-FD overlap was 6.3 (95 % CI, 4.8–8.4). Mean age (p?=?0.011) and epigastric pain (p?=?0.002) were more in overlap patients than FD alone, whereas epigastric pain syndrome subtype (p?<?0.009) was more prevalent in lone FD subjects. In the multivariate logistic analysis, early satiety (OR, 3.0; 95 % CI, 1.2–7.5; p?=?0.018) and epigastric pain (OR, 14.5; 95 % CI, 5.0–42.1; p?=?0.000) in FD patients appeared as independent risk factors for overlap. Bloating (p?=?0.026), <3 stools per week (p?=?0.050), abdominal pain reduced by defecation (p?=?0.002), abdominal pain severity score (p?=?0.004), and overall symptom frequency score (p?=?0.000) were more in overlap patients than IBS-alone patients. In IBS patients, bloating (OR, 3.6; CI, 2.0–6.5; p?=?0.000) was found as potential symptom associated with IBS-FD overlap.

Conclusion

FD was a less prevalent disorder than IBS in our community, and significant overlap existed between the two disorders. Early satiety, epigastric pain, and bloating were important factors associated with overlap.     

Prevention of colonic spasm using l-menthol in colonoscopic examination

Purpose

The detailed efficacy of intraluminal l-menthol for preventing colonic spasm is not known. The aim of this study was to evaluate the effectiveness of l-menthol in preventing colonic spasm during colonoscopy.

Methods

We analyzed 65 patients (mean age: 71.7 years; 49 men and 16 women) who were administered 0.8 % l-menthol (MINCLEA, Nihon Seiyaku, Tokyo, Japan) intraluminally for severe colonic spasm during colonoscopic examination at Kyoto Prefectural University of Medicine between February 2012 and May 2013. The efficacy of l-menthol was defined as the absence of colonic spasm during a period of 30 s, and its effect was evaluated at 30 s, 1 min, and 5 min after administration. Additionally, various characteristics of these patients were analyzed. Twenty-seven patients with severe colonic spasm were administered intraluminal water and assessed as controls.

Results

l-Menthol was effective in preventing colonic spasms in 60.0 %, 70.8 %, and 46.5 % of patients at 30 s, 1 min, and 5 min, respectively. In contrast, water was effective in 22.2 %, 29.6 %, and 48.1 % of patients at 30 s, 1 min, and 5 min, respectively. There was a significant difference about the efficacy at 30 s and 1 min between l-menthol and water (P?=?0.0009, P?=?0.0006).

Conclusions

l-Menthol (0.8 %) was effective in preventing colonic spasm during colonoscopic examination.     

Hepatic Steatosis Is Highly Prevalent in Hepatitis B Patients and Negatively Associated with Virological Factors

Background and Aims

The interaction between hepatitis B virus (HBV) infection and hepatic steatosis remains unclear. We aimed to explore the trend of prevalence of hepatic steatosis and its relationship with virological factors in HBV infected patients.

Methods

Consecutive untreated patients with chronic HBV infection at Shunde Hospital between 2002 and 2011 were included. Quantification of HBV replication markers was performed by enzyme immunoassay, real-time polymerase chain reaction assay and immunohistochemical staining. Hepatic steatosis was defined as at least 5 % hepatocytes affected.

Results

A total of 3,212 patients (2,574 men) with a mean age of 32 ± 9.3 years were analyzed. Serological testing showed detectable HBsAg in all, HBeAg in 63.8 % and HBV DNA in 78.4 % of patients. Liver biopsies demonstrated HBsAg- and HBcAg-positive immunostaining in 96.6 and 71 % patients, respectively. Hepatic steatosis was present in 554 (17.3 %) patients, with annual prevalence increased over time from 8.2 to 31.8 % (trend analysis, x ² = 51.657, P < 0.001). Compared to patients without steatosis, the percentages of serum HBeAg-positive and detectable HBV DNA, and intrahepatic HBsAg- and HBcAg-positive staining were decreased in steatosis patients (all P < 0.001). Adjusted for age and gender, intrahepatic HBsAg-positive staining remained as an independent factor associated with lower risk of steatosis (adjusted odds ratio 0.90, 95 % confidence interval 0.835, 0.971) in multivariate analysis.

Conclusions

Hepatic steatosis in HBV infected patients has been raging over the past decade, and it is negatively associated with intrahepatic expression of HBsAg. Lifestyle intervention may be needed to halt the onset of steatosis in chronic HBV infection.     

Kidney function as an underestimated factor for reduced health related quality of life in patients with Fabry disease

Background

Impairments of health related quality of life (HRQoL) are frequently observed in Fabry disease (FD) and are known to be related to neuropathic pain and cardiovascular events. This study aimed to explore the role of chronic kidney disease (CKD) in a large cohort of patients with FD.

Methods

In 96 patients (53% female; age 40?±?12 yrs) with genetically proven FD, HRQoL was assessed by the Medical Outcomes Study (SF-36) questionnaire. All patients were naïve to enzyme replacement therapy. Three categories for kidney dysfunction were chosen, eGFR ≥/<60 ml/min/1.73 m² or need of renal replacement therapy (RRT). Minor (e.g. arrhythmia, angina pectoris, etc.) and major (e.g. myocardial infarction, coronary artery bypass, stroke or implantable cardioverter-defibrillator) vascular events as well as pain and pain therapy were considered in linear regression analyses with the dimensions of HRQoL.

Results

Ten patients (10%) had impaired kidney function and a further nine were on RRT (9.4%). Kidney function and pain emerged as the main factors associated with lower scores on the SF 36, in particular on physical components (PCS beta-coefficients for CKD ?6.2, for RRT ?11.8, for pain ?9.1, p?<?0.05, respectively), while controlling for gender, vascular event and pain-therapy. Relationships were found for mental aspects of HRQoL. Age and history of vascular events were not related to HRQoL.

Conclusion

Cardiovascular events and pain are important factors related to HRQoL, social functioning and depression. Our study highlights impaired chronic kidney disease, in particular after initiation of RRT, as a strong determinant of reduced HRQoL in FD.

     

Prevalence of signs and symptoms suggestive of obstructive sleep apnea syndrome in Guangxi,China

Background

The prevalence, profiles, and potential risk factors of snoring and obstructive sleep apnea–hypopnea syndrome (OSAHS) in China are largely unknown.

Objectives

This study aims to investigate the prevalence, profiles, and potential risk factors for snoring and OSAHS in Guangxi, China, and the association between OSAHS and ethnicity.

Methods

Urban and rural population-based cluster samples were randomly selected in each of eight counties/cities. All residents aged 14 years or older in the selected clusters were interviewed using a standardized questionnaire. A subject was considered to have clinically diagnosed OSAHS if snoring was loud and habitual, breathing pauses were observed, and the subject experienced excessive daytime sleepiness.

Results

Among 12,742 sampled subjects, 10,819 completed the questionnaire (response rate?=?84.9 %). The overall OSAHS prevalence was 4.1 % (men, 5.7 % (5.1–6.3 %); women, 2.4 % (2.0–2.9 %); Zhuang people, 3.2 % (2.8–3.7 %); Han people 6.0 % (5.2–6.8 %).The overall rate of habitual snoring was 11.5 % (men, 17.1 % (16.1–18.1 %); women, 5.6 % (5.0–6.2 %)). Univariate analysis showed that the OSAHS prevalence was significantly higher among the following groups: urban residents, elderly individuals, smokers, drinkers, those with higher body mass indexes (BMI), those with more years of schooling, those with nasal problems, those whose parents are Han, and those who usually sleep in prone position. However, multiple logistic regression analysis revealed that only urban residency, age, smoking status, drinking status, and BMI were the risk factors for OSAHS.

Conclusions

OSAHS is prevalent in individuals aged 14 years or older in Guangxi, China. Han and Zhuang people differ significantly in their obstructive sleep apnea (OSA) prevalence, but this difference is explained by the combination of classic OSA risk factors.