肠易激综合症患者结肠组织中促肾上腺皮质激素释放因子受体表达的研究

目的 检测肠易激综合症（IBS）患者结肠组织中促肾上腺皮质激素释放因子受体（CRFR）1及CRFR2的表达,探讨其与IBS发病的关系,从而为靶向治疗IBS提供依据.方法 分别采集15例腹泻型IBS（D-IBS）患者、15例便秘型IBS（C-IBS）患者和10例正常健康人结肠组织标本,采用Elivision（TM）PLUS/HRP免疫组化染色方法和Western blot测定CRFR1、CRFR2在各组结肠组织中的蛋白表达.结果 实验结果显示,正常对照组CRFR1和CRFR2免疫组化染色以浅黄色为主,分布范围局限,平均光密度值分别为（0.254±0.099）和（0.201±0.030）;D-IBS组中CRFR1以深或棕黄色为主,分布范围较为广泛,平均光密度值为（0.384±0.048）,显著高于C-IBS组（0.144±0.077）及正常对照组（P〈0.01）;C-IBS组中CRFR2染色以深或棕黄色为主,分布范围较为广泛,平均光密度值为（0.322±0.022）,显著高于D-IBS组（0.162±0.023）（P〈0.01）及正常对照组（P〈0.05）.Western blot结果显示,D-IBS组CRFR1蛋白表达明显高于C-IBS组和正常对照组;C-IBS组CRFR2表达高于D-IBS组和正常对照组.结论 不同亚型IBS患者其CRFR表达的亚型亦不同,提示不同亚型IBS的发生可能与患者结肠组织中CRFR1、CRFR2的表达水平有关.     

Gender differences in self-reported constipation characteristics,symptoms, and bowel and dietary habits among patients attending a specialty clinic for constipation

Objectives: This study assessed gender differences in the frequency of various characteristics of constipation, constipation-specific symptoms, and bowel and dietary habits, as well as the effects of independent but associated risk factors.Methods: A cross-sectional study of patients aged ≥18 years with a primary diagnosis of constipation (ie, constipation, slow-transit constipation, outlet dysfunction constipation) was conducted at a tertiary referral center; patients were excluded if they had a primary diagnosis of fecal incontinence. Patients completed both a clinical questionnaire to obtain information on demographic characteristics and medical history and an unvalidated self-report questionnaire relating to the characteristics and symptoms of constipation as well as various bowel and dietary habits. Likert scales were used to assess 4 characteristics of constipation (frequency of constipation, duration of constipation symptoms of ≥1 month, bowel movement frequency, stool consistency) and the frequency of occurrence of 6 constipation symptoms (abdominal pain, abdominal bloating, incomplete evacuation, unsuccessful attempts at evacuation, pain with evacuation, straining with evacuation). The bowel habits that were evaluated included time spent at each evacuation; frequency of needing to change position to evacuate; use of anal digitation to evacuate; and the use of laxatives, enemas, stool softeners, foods, drinks, or other aids. The dietary habits that were evaluated included use of dietary fiber, use of fiber supplements, and water intake.Results: Of the 518 patients, the majority were female (79.0%), white (76.3%), and employed (62.0%), with a mean (SD) age of 52.4 (16.5) years (range, 18.6–91.5 years). After controlling for a number of related conditions, women were more likely than men to have infrequent bowel movements (adjusted odds ratio [AOR] = 2.97; 95% CI, 1.67–5.28), abnormal stool consistency (ie, hard or pelletlike stools) (AOR = 3.08; 95% CI, 1.80–5.28), and a longer duration of constipation symptoms (AOR = 2.00; 95% CI, 1.05–3.82). In addition, women were more likely to report an increased frequency of occurrence of abdominal pain (AOR = 2.22; 95% CI, 1.22–4.05), bloating (AOR = 2.65; 95% CI, 1.50–4.70), unsuccessful attempts at evacuation (AOR = 1.74; 95% CI, 1.01–3.00), and the use of anal digitation to evacuate stool (AOR = 3.37; 95% CI, 1.15–9.90).Conclusions: The women in this specialty-based clinic study experienced a number of constipation symptoms and abnormal bowel habits more frequently than did men. These findings warrant replication in both population- and specialty clinic-based samples. In addition, the physiologic mechanisms that underlie these gender differences warrant investigation.     

Development and Validation of a Biomarker for Diarrhea-Predominant Irritable Bowel Syndrome in Human Subjects

Diarrhea-predominant irritable bowel syndrome (IBS) is diagnosed through clinical criteria after excluding “organic” conditions, and can be precipitated by acute gastroenteritis. Cytolethal distending toxin B (CdtB) is produced by bacteria that cause acute gastroenteritis, and a post-infectious animal model demonstrates that host antibodies to CdtB cross-react with vinculin in the host gut, producing an IBS-like phenotype. Therefore, we assessed circulating anti-CdtB and anti-vinculin antibodies as biomarkers for D-IBS in human subjects. Subjects with D-IBS based on Rome criteria (n=2375) were recruited from a large-scale multicenter clinical trial for D-IBS (TARGET 3). Subjects with inflammatory bowel disease (IBD) (n=142), subjects with celiac disease (n=121), and healthy controls (n=43) were obtained for comparison. Subjects with IBD and celiac disease were recruited based on the presence of intestinal complaints and histologic confirmation of chronic inflammatory changes in the colon or small intestine. Subjects with celiac disease were also required to have an elevated tTG and biopsy. All subjects were aged between 18 and 65 years. Plasma levels of anti-CdtB and anti-vinculin antibodies were determined by ELISA, and compared between groups. Anti-CdtB titers were significantly higher in D-IBS subjects compared to IBD, healthy controls and celiac disease (P<0.001). Anti-vinculin titers were also significantly higher in IBS (P<0.001) compared to the other groups. The area-under-the-receiver operating curves (AUCs) were 0.81 and 0.62 for diagnosis of D-IBS against IBD for anti-CdtB and anti-vinculin, respectively. Both tests were less specific in differentiating IBS from celiac disease. Optimization demonstrated that for anti-CdtB (optical density≥2.80) the specificity, sensitivity and likelihood ratio were 91.6%, 43.7 and 5.2, respectively, and for anti-vinculin (OD≥1.68) were 83.8%, 32.6 and 2.0, respectively. These results confirm that anti-CdtB and anti-vinculin antibodies are elevated in D-IBS compared to non-IBS subjects. These biomarkers may be especially helpful in distinguishing D-IBS from IBD in the workup of chronic diarrhea.     

Women tolerate drug therapy for coronary artery disease as well as men do,but are treated less frequently with aspirin, β-blockers,or statins

Background: Women have worse morbidity, mortality, and health-related quality-of-life outcomes associated with coronary artery disease (CAD) compared with men. This may be related to underutilization of drug therapies, such as aspirin, β-blockers, angiotensin-converting enzyme (ACE) inhibitors, or statins. No studies have sought to describe the relationship of gender with adverse reactions to drug therapy (ADRs) for CAD in clinical practice.Objective: The aim of this study was to determine the prevalence of ADRs associated with common CAD drug therapies in women and men in clinical practice.Methods: In a cohort of consecutive outpatients with CAD, detailed chart abstraction was performed to determine the use of aspirin, β-blocker, ACE inhibitor, and statin therapy, as well as the ADRs reported for these treatments. Baseline clinical characteristics were also determined to identify the independent association of gender with use of standard drug treatments for CAD.Results: Consecutive patients with CAD (153 men, 151 women) were included in the study. Women and men were observed to have a similar prevalence of cardiac risk factors and comorbidities, except that men had significantly higher prevalence of atrial fibrillation (30 [19.6%] men vs 15 [9.9%] women; P = 0.03) and significantly lower mean (SD) high-density lipoprotein cholesterol concentrations (45 [16] mg/dL for men vs 55 [19] mg/dL for women; P < 0.001). No significant differences were observed between the sexes in the prevalence of ADRs; however, significantly fewer women than men were treated with statins (118 [78.1%] vs 139 [90.8%], respectively; P = 0.003). After adjusting for clinical characteristics, women were also found to be less likely than men to receive aspirin (odds ratio [OR] = 0.164; 95% CI, 0.083–0.322; P = 0.001) and β-blockers (OR = 0.184; 95% CI, 0.096-0.351; P = 0.001).Conclusions: Women and men experienced a similar prevalence of ADRs in the treatment of CAD; however, women were significantly less likely to be treated with aspirin, β-blockers, and statins than were their male counterparts. To optimize care for women with CAD, further study is needed to identify the cause of this gender disparity in therapeutic drug use.     

Association Between Serum Uric Acid Level and Body Mass Index in Sex- and Age-Specific Groups in Southwestern China

Objective: To investigate the sex- and age-specific association between serum uric acid level and body mass index (BMI).Methods: A total of 144,856 subjects aged 20 to 79 years were enrolled in this cross-sectional study. Serum uric acid level, renal function, hepatic function, and lipid profile were investigated.Results: The prevalence of hyperuricemia decreased with age in men but increased in women. In men, the correlation coefficient between the serum urate level and BMI declined steadily with age. Underweight was associated with a 53 to 68% and a 66% lower prevalence of hyperuricemia in men aged 20 to 69 years and in women aged 20 to 29 years, respectively. Overweight and obesity were correlated with a higher odds ratio (OR) (95% confidence interval &lsqb;CI]) for hyperuricemia in both genders. In individuals with overweight or obesity, younger subjects had a higher OR (95% CI) for hyperuricemia than older subjects. Among subjects aged 20 to 59 years, as they gained weight, the OR (95% CI) for hyperuricemia increased faster in women than in men compared with their respective normal-weight controls.Conclusion: Underweight was associated with a lower prevalence of hyperuricemia in men aged ≤69 years. In individuals with overweight or obesity, younger subjects were more likely to develop hyperuricemia than older subjects. With active weight gain, the likelihood for developing hyperuricemia increased faster in women than in men compared with their respective normal-weight controls.Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; BMI = body mass index; CI = confidence interval; eGFR = estimated glomerular filtration rate; HDL-C = high-density-lipoprotein cholesterol; LDL-C = low-density-lipoprotein cholesterol; OR = odds ratio     

Differences in associations between markers of antioxidative defense and asthma are sex specific

Background: Lungs are exposed to high levels of oxygen, air pollutants, and smoke, all of which stimulate the production of reactive oxygen species (ROS). In addition, inflammatory cells produce ROS, and thus there may be increased demand for antioxidants, including antioxidant enzymes, in inflammatory lung diseases such as asthma. Sex-specific differences have been noted for asthma, which in postpubertal subjects is predominantly found in females. These sex-specific differences may be associated with differences on the molecular level as well.Objective: The aim of this cross-sectional study was to examine associations between markers of antioxidative defense and asthma, and to investigate whether these associations were different between women and men.Methods: Based on the European Community Respiratory Health Survey protocol, subjects were enrolled in a study of asthma risk factors. The multicenter study was conducted in 5 west Danish counties between 2003 and 2006, and the subjects were recruited as a case-enriched random sample of 10,000 Danish inhabitants aged 20 to 44 years selected by their civil registration number. Participants were identified by positive answers to asthma questions on a screening questionnaire, random sampling, or both. Serum selenium concentrations and antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase [GPX], glutathione reductase [GR], and glucose-6-phosphate dehydrogenase [G6PD]) in erythrocytes were measured. Asthma was defined as either current asthma symptoms with bronchial hyperresponsiveness (BHR) or a continuous asthma score based on 8 questions.Results: A total of 1191 mostly white women and men (mean [SD] age, 34.0 [7.1] and 35.1 [7.1] years, respectively) were enrolled in the study. Current asthma symptoms were present in 29.9% (200/670) of women and 22.5% (117/521) of men, with women reporting more positive answers (51.1% vs 40.9%, respectively; P < 0.01) to asthma questions. Serum selenium concentrations were measured in 1151 subjects (640 women, 511 men), and antioxidant enzyme activities were measured in 295 subjects (161 women, 134 men). Women had higher enzyme activities of most antioxidant enzymes (GPX, P = 0.006; GR, P < 0.001; and G6PD, P = 0.009) than did men. Although the serum selenium concentration was inversely associated with asthma in both sexes, there was a female preponderance, with 3.5% lower serum selenium in subjects with current asthma symptoms with BHR (n = 77) compared with controls (n = 287). GR activity was associated with asthma in men, with 5.7% higher enzyme activity in subjects with current asthma symptoms with BHR (n = 14) compared with controls (n = 77). However, a significant interaction with gender was observed for analyses of GR (P = 0.02), but not for analyses of selenium.Conclusions: In this study of asthma risk factors, women had higher levels of enzyme activities than did men in a randomly selected Danish population, and sex-specific differences were found in the associations between markers of antioxidative defense and asthma.     

Blastocystis Is Associated with Decrease of Fecal Microbiota Protective Bacteria: Comparative Analysis between Patients with Irritable Bowel Syndrome and Control Subjects

Blastocystis is a protistan parasite living in the digestive tract of many animals, including humans. This highly prevalent intestinal parasite is suspected to be linked to Irritable Bowel Syndrome (IBS), a chronic functional bowel disorder. Here, we first compared the prevalence of Blastocystis among 56 IBS patients (40 IBS with constipation (IBS-C), 9 IBS with diarrhea (IBS-D), 4 mixed IBS (IBS-M) and 3 unsubtyped IBS (IBS-U) according to the Rome III criteria) and 56 control (i.e. without any diagnosed chronic or acute gastrointestinal disorder) subjects. The highest prevalence of Blastocystis spp. was observed in the IBS group, but was only statistically significant in men (36.8% in the IBS group versus 4.8% in the control group). We then conducted a meta-analysis including epidemiological studies attempting to determine whether Blastocystis carriage could be linked to IBS, and highlighted that IBS patients had a relative risk of 2.34 to be infected by Blastocystis when compared to non-IBS subjects. We also looked for Dientamoeba fragilis, which is often associated with IBS, and identified this parasite only in some IBS patients (n = 6/56). Several studies provided evidence for a major role of the gut microbiota in the pathophysiology of IBS. Thus, we investigated the possible impact of Blastocystis carriage on the enteric bacterial community through quantification of 8 major bacterial groups from the enteric flora. Our data indicated that men with IBS-C had a significant decrease in Bifidobacterium sp. when infected by Blastocystis. Interestingly, in control subjects (i.e. without any gastrointestinal disorder) positive for Blastocystis, Faecalibacterium prausnitzii, which is known for its anti-inflammatory properties, was significantly decreased in men. Our results support the hypothesis that Blastocystis might be linked to the pathophysiology of IBS-C and intestinal flora imbalance.     

Symptoms of a first acute myocardial infarction in women and men

Background: Many studies have compared women and men for symptoms of acute myocardial infarction (AMI), but findings have been inconsistent, largely because of varying inclusion criteria, different study populations, and different methods.Objective: The purpose of this study was to analyze gender differences in symptoms in a well-defined, population-based sample of women and men who experienced a first AMI.Methods: Information on symptoms was collected from the medical charts of all patients with a first AMI, aged 25 to 74 years, who had taken part in the INTERGENE (Interplay Between Genetic Susceptibility and Environmental Factors for the Risk of Chronic Diseases) study. INTERGENE was a population-based research program on risk factors for cardiovascular disease. Medical charts were reviewed for each patient to determine the symptoms of AMI, and the prevalence of each symptom was compared according to sex.Results: The study included 225 patients with a first AMI: 52 women and 173 men. Chest pain was the most common symptom, affecting 88.5% (46/52) of the women and 94.8% (164/173) of the men, with no statistically significant difference between the sexes. Women had significantly higher rates of 4 symptoms: nausea (53.8% [28/52] vs 29.5% [51/173]; age-adjusted odds ratio [OR] = 2.78; 95% CI, 1.47–5.25), back pain (42.3% [22/52] vs 14.5% [25/173]; OR = 4.29; 95% CI, 2.14–8.62), dizziness (17.3% [9/52] vs 7.5% [13/173]; OR = 2.60; 95% CI, 1.04–6.50), and palpitations (11.5% [6/52] vs 2.9% [5/173]; OR = 3.99; 95% CI, 1.15–13.84). No significant gender differences were found in the proportions of patients experiencing arm or shoulder pain, diaphoresis, dyspnea, fatigue, neck pain, abdominal pain, vomiting, jaw pain, or syncope/lightheadedness. No significant differences were found in the duration, type, or location of chest pain. The medical charts listed numerically more symptoms in women than in men; 73.1% (38/52) of the women but only 48.0% (83/173) of the men reported >3 symptoms (age-adjusted OR = 3.26; 95% CI, 1.62–6.54).Conclusions: Chest pain is the most common presenting symptom in both women and men with AMI. Nausea, back pain, dizziness, and palpitations were significantly more common in women. Women as a group displayed a greater number of symptoms than did men.     

Predictors of depressive symptoms post-acute coronary syndrome

Objective: We examined the influence of gender on the prevalence of acute coronary syndrome (ACS) and the severity of depressive symptoms post-ACS.Methods: Patients received a Zung self-assessment questionnaire at hospital discharge for unstable angina (UA) or acute myocardial infarction (AMI) and returned it by mail. Major depressive symptoms were diagnosed based on a summed depressive symptoms (SDS) score of >50. Depressive symptomatology was modeled by stepwise multivariable logistic regression with the following predictors: gender, age, hypertension, diabetes mellitus, history of smoking, hypercholesterolemia, peripheral vascular disease, prior stroke, prior myocardial infarction (MI), and prior percutaneous coronary intervention or coronary artery bypass graft surgery. We also modeled severity of depressive symptoms via stepwise multiple linear regression with the same predictor variables.Results: A total of 944 patients were surveyed: 716 men and 228 women, mean (SD) age, 67 (13) years and 71 (12) years, respectively. Of these patients, 250 (35%) men and 103 (45%) women had depressive symptoms (P = 0.005). No significant difference was observed between men and women in rates of cardiac catheterization; severity of coronary artery disease; treatment with antiplatelet agents, β-blockers, angiotensin-converting enzyme inhibitors, or statins; or percutaneous or surgical revascularization rates during or post-ACS. Significant predictors of the presence of depressive symptoms were female gender (odds ratio [OR] = 1.64; 95% CI, 1.19-1.28), diabetes mellitus (OR = 1.42; 95% CI, 1.03-1.97), prior MI (OR = 1.56; 95% CI, 1.15-2.20), and smoking (OR = 1.41; 95% CI, 1.01-1.97). Variables significantly associated with a higher severity of depressive symptoms were female gender, prior MI, smoking, and stroke. Men with prior MI had significantly higher mean (SD) SDS scores than did men without prior MI in all age groups (48.4 [11] vs 44.6 [11], respectively; P < 0.001). In addition, significantly more men with prior MI had depressive symptoms compared with those without prior MI (45% vs 32%; P = 0.001). However, prior MI did not appear to affect SDS scores in women (49.1 [12] for prior MI vs 48.5 [12] for no prior MI; P = NS), and there was no significant difference in the percentage of women who had depressive symptoms with or without a history of prior MI. Depressive symptoms were much more severe in women with UA (SDS = 49.0 [12]) compared with women with AMI (SDS = 45.0 [12]; P = NS), or men with AMI (45.0 [12]; P = 0.004) or UA (46.0 [11]; P = 0.007) (analysis of variance, P = 0.003).Conclusions: Female gender is a significant independent predictor of depressive symptoms and their severity post-UA and post-AMI. History of prior MI is associated with a higher frequency and severity of depressive symptoms in men. These findings call for routine screening for depressive symptoms in men with prior MI and in women who present with ACS.     

Interrelations and associations of serum levels of steroids and pituitary hormones with markers of insulin resistance,inflammatory activity,and renal function in men and women aged >70 years in an 8-year longitudinal study of opposite-sex twins

Background: The physiological serum levels of steroids and pituitary hormones in older men and women have been sparsely reported in the literature.Objectives: The aims of this study were to investigate the normal variation and sex differences in steroids and pituitary hormones in those aged >70 years, and to study the interrelation between these hormones and indicators of the metabolic syndrome, inflammatory activity, and renal function.Methods: The investigation comprised a population-based sample of pairs of white opposite-sex twins from the Swedish Twin Registry. At baseline in 1996 and at the 8-year follow-uup in 2004, serum levels of progesterone, cortisol, testosterone, estradiol, follicle-stimulating hormone, luteinizing hormone, prolactin, creatinine, C-reactive protein (CRP), and urea were analyzed. Serum levels of insulin and cystatin were analyzed only at the follow-up.Results: The study sample included 219 men and 183 women aged 71 to 80 years (mean [SD], 74.5 [2.5] years) at baseline in 1996, and 127 men and 135 women at follow-uup in 2004. At baseline, in both men and women, the variation of progesterone in serum was positively correlated with that of estradiol (men: r = 0.226, P < 0.01; women: r = 0.115, P = NS), testosterone (men: r = 0.178, P < 0.01; women: r = 0.315, P < 0.001), and cortisol (men: r = 0.314, P < 0.001; women: r = 0.296, P < 0.001). The values of progesterone and other steroid hormones were associated with markers of insulin resistance (iie, insulin, waist circumference), inflammatory activity (ie, CRP) for progesterone (men: r = 0.267, P < 0.001; women: r = 0.150, P < 0.05), and renal function (ie, creatinine) for progesterone (men: r = 0.424, P < 0.001; women: r = 0.212, P < 0.01). Estradiol and prolactin were associated with insulin resistance, inflammation, and renal function. Furthermore, progesterone was associated with prolactin (men: r = 0.275, P < 0.001; women: r = 0.172, P < 0.05).. Among both men and women, there was a strong correlation between testosterone and estradiol (men: r = 0.753, P < 0.001; women: r = 0.526, P < 0.001); in women, there was also a link between testosterone and cortisol at follow-up (r = 0.340, P < 0.01). For progesterone, there was a significant correlation between the values of the co-twins (in 1996: r = 0.16, P < 0.05; in 2004: r = 0.45, P < 0.001). Higher serum levels of progesterone (2.0 [0.7] nmol/L in men and 1.7 [0.8] nmol/L in women) and prolactin (6 [5] μg/L in men and 8 [10] μg/L in women) were found among those who were deceased at follow-up compared with survivors (progesterone: 1.8 [0.5] nmol/L in men and 1.4 [0.6] nmol/L in women, P < 0.01; prolactin: 4 [3] μg/L in men and 5 [2] μg/L in women, P < 0.001).Conclusions: In this study of opposite-sex Swedish twins aged >70 years, there was a sex difference in the serum levels of steroids and pituitary hormones between men and women. Progesterone and other steroid hormones were associated with markers of insulin resistance, inflammatory activity, and renal function. Progesterone and prolactin levels were associated with increased risk of mortality in this sample.     

Sex differences in prefrontal hemodynamic response to mental arithmetic as assessed by near-infrared spectroscopy

Background: Sex differences in cognitive tasks have been widely investigated. With brain-imaging techniques, the functions of the brain during the performance of tasks can be examined.Objective: Mental arithmetic and near-infrared spectroscopy (NIRS) were used to assess sex differences in prefrontal area activation in a functional brain study.Methods: Healthy college students were recruited to perform 2 mental arithmetic tasks. In the first (easy) task, students had to subtract a 1-digit number from a 3-digit number. In the second (difficult) task, they had to subtract a 2-digit number from a 3-digit number. Changes in the concentration of oxygenated hemoglobin (oxy-Hgb) in the prefrontal area during the tasks were measured with NIRS.Results: Thirty students (15 men, 15 women; mean [SD] age: 24.9 [2.2] and 24.3 [2.6] years, respectively) were recruited from Southeast University, Nanjing, China, to participate in the study. The concentration of oxy-Hgb increased during both mental arithmetic tasks (difficult task vs easy task, mean [SD] % arbitrary units: 4.36 [4.38] vs 2.26 [2.82]; F_1,28 = 222.80; P < 0.01). Significant interactions of task x sex (F_1,28 = 82.95), time × sex (F_1,28 = 34.48), task × time (F_1,28 = 222.57), and task × time × sex (F_1,28 = 83.09) were obtained (all, P < 0.01). However, for the 2 tasks, no significant differences between men and women were observed in the mean (SD) response time (men vs women, sec: 3.60 [0.74] vs 3.56 [0.49] for the easy task, 6.55 [0.77] vs 6.44 [0.75] for the difficult task; F_1,28 = 0.67; P = NS) or accuracy rate (men vs women, %: 95.33 [7.40] vs 92.77 [8.80] for the easy task, 62.67 [28.56] vs 54.67 [18.75] for the difficult task; F_1,28 = 0.54; P = NS). Male students showed neural efficiency (less prefrontal activation in subjects with better performance) during the difficult task.Conclusions: In these subjects, sex differences in prefrontal response when performing mental arithmetic were associated with the intensity of the task. Compared with men, women had greater efficiency in task performance (ie, less activation or oxygen consumption for equal performance).     

The Association of Thyroid Hormones and Tsh with the Metabolic Syndrome in Euthyroid Taiwanese Individuals

Objective: There are conflicting studies in euthyroid males and females regarding associations between thyroidrelated hormones and parameters of the metabolic syndrome (MetS). We investigated the association between serum thyroid hormones and thyroid-stimulating hormone (TSH) concentrations and MetS in euthyroid men and women.Methods: Taiwanese subjects aged 20 to 65 years who had undergone a voluntary health examination at a preventive examination agency in Taipei were enrolled in this cross-sectional study. The definition of MetS was suggested by the Bureau of Health Promotion, Department of Health, Taiwan. Euthyroidism was defined as TSH and free thyroxine (FT4) levels within the normal reference ranges while not taking any thyroid medication. We conducted multiple logistic regression to identify the ability of serum triiodothyronine (T3), FT4, and TSH concentrations to identify the relative risk for the presence of MetS and components of the MetS in euthyroid Taiwanese individuals.Results: A total of 8,207 Taiwanese subjects (mean age: men, 45.3 ± 9.9 years; women, 43.5 ± 9.3 years) were enrolled in this study. A total of 1,672 subjects (20.4%) were defined as having MetS; these subjects had significantly higher (P<.0001) mean age (48.4 ± 9.1 years vs. 43.6 ± 10.7 years), prevalence of men (78.7% vs. 53.4%), and smoking (16.8% vs. 11.6%) than those without MetS. The median TSH, FT4, and T3 levels in all subjects were 1.70 mIU/L, 1.41 ng/dL, and 1.20 ng/mL, respectively. Higher T3 and lower FT4 values rather than TSH increased the odds ratio for MetS in men and women after adjusting for smoking and age, particularly for the association of T3 and MetS in women (uppermost quartile versus lowermost quartile: odds ratio, 2.4; 95% confidence interval, 1.6 to 3.5; P for trend <.0001).Conclusion: In euthyroid Taiwanese men and women, relatively high serum T3 concentrations was most strongly associated with the presence of the MetS; relatively low serum T4 was less strongly related, and serum TSH levels were not associated with the MetS. It is not known if the relationship of serum T3 and T4 to the MetS is causal.Abbreviations:BMI = body mass indexFT4 = free thyroxineMetS = metabolic syndromeOR = odds ratioT3 = triiodothyronineTSH = thyroid-stimulating hormoneWC = waist circumference     

Gender-specific differences in bladder cancer: A retrospective analysis

Background: A higher incidence of bladder cancer has been reported in men compared with women. Clinical gender differences have been observed but are less well described.Objective: This retrospective analysis further examines clinical differences in the development and manifestation of bladder cancer between men and women.Methods: Consecutive male and female patients with bladder cancer treated between 1969 and 1997 at a single center (University Hospital of Innsbruck, Innsbruck, Austria) were included in the study. Patient characteristics regarding age, tumor classification, localization, and recurrence were compared between male and female patients. Statistical analysis was conducted using the t test, the χ² test, and the Kaplan-Meier method, with the log-rank test for subgroup analysis.Results: In the 1269 patients (876 men, 393 women) who were examined, 1744 tumors were found. The male-to-female bladder cancer incidence ratio was 2.2:1. Tumors were diagnosed at a significantly younger age in men than in women (mean age: 62 years vs 67 years, respectively; P < 0.001). No difference in the histology of tumors was observed between the sexes. Muscle-invasive tumors more frequently occurred in men than in women (39.8% vs 34.5%; P = NS). In men compared with women, primary tumors were more aggressive (grade 2, 36.6% vs 28.2%; P < 0.001) and tumor recurrences were more invasive (59.0% vs 57.8%; P = NS). Tumors were more often located in the urethra in men than in women (43 [3.4%] vs 9 [1.8%]; P = 0.034), the trigonum (246 [19.8%] vs 75 [14.9%]; P < 0.001), and the bladder dome or vault (128 [10.3%] vs 37 [7.4%]; P = 0.015). Generally, no difference in survival rate was observed between the sexes; only in the subgroup of muscle-invasive tumors (n = 455) did women have a worse overall survival rate than did men (P = 0.022).Conclusions: Clinical gender differences in bladder cancer appear to have a higher incidence in men than in women. In this analysis, women were older at the age of detection, but had less-invasive and less-aggressive tumors than did men. However, women with muscle-invasive disease had a worse overall survival rate than did men in the same subset.     

Blood oxidative stress biomarkers: influence of sex,exercise training status,and dietary intake

Background: Sex and lifestyle factors are known to influence the oxidation of protein, lipids, and DNA. Biomarkers such as protein carbonyls (PC), malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHdG) have been commonly used in an attempt to characterize the oxidative status of human subjects.Objective: This study compared resting blood oxidative stress biomarkers, in relation to exercise training status and dietary intake, between men and women.Methods: Exercise-trained and sedentary men and women (with normal menstrual cycles; reporting during the early follicular phase) were recruited from the University of Memphis, Tennessee, campus and surrounding community via recruitment flyers and word of mouth. Participants were categorized by sex and current exercise training status (ie, trained or untrained). Each completed a detailed 5-day food record of all food and drink consumed. Diets were analyzed for kilocalories and macro- and micronutrient (vitamins C, E, A) intake. Venous blood samples were obtained at rest and analyzed for PC, MDA, and 8-OHdG.Results: In the 131 participants (89 men, of whom 74 were exercise trained and 15 untrained, and 42 women, of whom 22 were exercise trained and 20 untrained; mean [SD] age, 24 [4] years), PC did not differ significantly between trained men and women or between untrained men and women. However, trained participants had significantly lower plasma PC (measured in nmol · mg protein^-1) (mean [SEM] 0.0966 [0.0055]) than did untrained participants (0.1036 [0.0098]) (P < 0.05). MDA levels (measured in μmol · L^-1) were significantly lower in trained women (0.4264 [0.0559]) compared with trained men (0.6959 [0.0593]); in trained men and women combined (0.5621 [0.0566]) compared with untrained men and women combined (0.7397 [0.0718]); and in women combined (0.5665 [0.0611]) compared with men combined (0.7338 [0.0789]) (P < 0.05 for all comparisons). No significant differences were noted between any groups for 8-OHdG. Neither PC nor 8-OHdG were correlated to any dietary variable, with the exception of PC and percent of protein in untrained men (r = 0.552; P = 0.033). MDA was positively correlated to protein intake and negatively correlated to percent of carbohydrate and vitamin C intake, primarily in trained men (P ≤ 0.03).Conclusions: In this sample of young healthy adults, oxidative stress was lower in women than in men and in trained compared with untrained individuals, particularly regarding MDA. With the exception of MDA primarily in trained men, dietary intake did not appear to be correlated to biomarkers of oxidative stress.     

The influence of gender on adults admitted for asthma

Background: In the United States, the prevalence of asthma is not only higher than in most other countries, it also varies greatly between diverse populations. Only limited data exist that examine the variation of outcomes by gender in patients admitted to a hospital for asthma.Objective: This study assessed outcome differences based on gender in adults who were admitted nationally with the primary diagnosis of asthma.Methods: A retrospective cohort study was conducted of all patients who were admitted to a hospital with the primary diagnosis of asthma in 2002-2005 and were reported in the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project. Patients were excluded if they were aged <18 years or had an additional diagnosis of chronic obstructive pulmonary disease.Results: A total of 590,410 patients (439,991 women, 150,419 men) were included in the study. Patients admitted for asthma were significantly more likely to be female (P < 0.05). Women were significantly older compared with men (mean [SD], 48.5 [17.4] vs 44.6 [17.0] years, respectively), had a longer length of stay (3.44 vs 2.84 days), were more likely to be white (37.9% vs 34.2%), and had a higher total cost of admission ($10,575 vs $9390) (all, P < 0.05). Women were more likely than men to need a tracheostomy (adjusted odds ratio [AOR] = 2.04; 95% CI, 1.77-2.35) and to have a bronchoscopy (AOR =1.12; 95% CI, 1.05-1.21). Men were significantly more likely than women to have arterial blood gases performed (AOR = 1.15; 95% Cl, 1.05-1.27) and to be intubated (AOR = 1.18; 95% Cl, 1.10-1.26) (both, P < 0.05). Men were significantly more likely to be admitted as an emergency admission (AOR = 1.10; 95% Cl, 1.04-1.18) and to die during hospitalization (AOR =1.69; 95% CI, 1.41-2.03).Conclusion: Although they were less likely to be admitted to a hospital, men were more likely to be admitted as an emergency and to experience worse outcomes compared with women, in this study of adults with asthma in the United States.     

Gender Determines Serum Free Cortisol: Higher Levels in Men

Objective: Because only the free fraction of serum cortisol can readily access glucocorticoid receptors, we investigated whether or not a gender-related difference in serum free cortisol (FC) exists in the basal and adrenocorticotropic hormone (ACTH)-stimulated state.Methods: Serum total cortisol (TC) and FC were measured in 323 subjects (175 men; 148 women). Additionally, the low-dose 1-μg ACTH test was performed in 56 subjects (30 women, 26 men). Subjects were healthy volunteers, recruited in a preventive medicine screening program and an outpatient clinic.Results: Overall, basal serum TC and FC level were ~18 and ~33%, respectively, higher in men than in women (TC, 14.5 ± 0.33 μg/dL vs. 12.3 ± 0.33 μg/dL; P<.0001; FC, 0.68 ± 0.02 μg/dL vs. 0.51 ± 0.02 μg/dL; P<.0001). The higher FC in men relative to women was apparent across a wide age range (17 to 86 years) and persisted after adjustment for age and body mass index. The FC fraction (%FC, out of TC) was concordantly higher in men (5.4 ± 0.09% vs. 4.8 ± 0.3%; P = .046). FC was not related to the estimated menopausal status (women age below and above 47, 50, or 53 years). ACTH-stimulated FC levels were significantly higher in men compared to women, as reflected by the area under the response curve (49.4 ± 3.4 μg × min vs. 39.6 ± 2.2 μg × min; P = .0014).Conclusion: Gender is an unrecognized determinant of serum FC in humans. The possibility of lifelong exposure to the higher bioactive fraction of cortisol under basal conditions or daily stress involving ACTH stimulation should be further investigated in the context of gender-related phenotypic features such as “android” (visceral) fat deposition and longevity.Abbreviations:ACTH = adrenocorticotropic hormoneBMI = body mass indexCBG = cortisol-binding globulinFC = free cortisolHPA = hypothalamic-pituitary-adrenalTC = total cortisol     

Female survival advantage relates to male inferiority rather than female superiority: A hypothesis based on the impact of age and stroke severity on 1-week to 1-year case fatality in 40,155 men and women

Background: It is generally believed that differences in age, stroke characteristics, and cardiovascular risk factors account for observed sex-specific differences in stroke survival.Objectives: We aimed to study female stroke survival advantage before and after the average age of menopause, and whether female survival advantage applies only to patients for whom stroke is the most likely cause of death.Methods: The Danish National Indicator Project, a registry designed to list all hospitalized stroke patients in Denmark beginning in March 2001, had 40,155 registered patients as of February 2007. All registered patients had undergone evaluation including stroke severity (as measured by the Scandinavian Stroke Scale [SSS], using a total score of 0–58, in which lower scores indicate more severe strokes), computed tomography, and cardiovascular risk factors. Patients were followed from admission until death or censoring. Case fatality (stratified by 1 week, 1 month, 3 months, and 1 year) in men and women was correlated with age and stroke severity. Adjustment for cardiovascular risk factors was performed by means of multivariate regression analysis.Results: A total of 20,854 (51.9%) men and 19,301 (48.1%) women were registered. Women were significantly older than men at the time of stroke (74.5 vs 69.7 years, respectively; P < 0.001) and had signficantly more severe strokes, as expressed by the mean SSS score (39.6 vs 43.3; P < 0.001). Stratification of 1-week to 1-year case fatality according to age and stroke severity indicated that women survived significantly better than men from the mid-fifties onward, when controlling for age, stroke severity, and cardiovascular risk factor profile. The observed female survival advantage increased with age. The female survival advantage was seen in patients with severe as well as mild strokes, but not in those younger than age 50 years.Conclusions: Our findings dispute the effects of female sex hormones as the underlying cause of female survival superiority over men. Instead, we propose the hypothesis that the progressive deficiency of male sex hormones (testosterone), beginning in men in middle age, is the underlying cause of the gap in survival rates between men and women. Accordingly, the female survival advantage is rooted in male inferiority rather than innate female superiority.     

Effects of gender and depression on oral medication adherence in persons with type 2 diabetes mellitus

Background: In a range of chronic conditions including diabetes, it has been observed that depressive symptoms may be associated with nonadherence to medications.Objective: The objective of the study was to determine the main effects, and interactive effect, of depression and gender on patients adherence to oral diabetes medications.Methods: A cross-sectional design was employed, in which persons with type 2 diabetes mellitus completed a questionnaire regarding medication use behaviors, depressive symptoms (measured by the 8-item Patient Health Questionnaire [PHQ-8]), health beliefs, and demographics. A 2 x 2 factorial analysis of variance was used to determine the effects of gender and depression on medication adherence after adjusting for age, education, self efficacy, social support, and number of doses of diabetes medications.Results: Of the 391 respondents who completed the questionnaire, 73 (18.7%) were categorized as having depression (ie, PHQ-8 score >10). Overall, women (n = 196) had a mean (SD) score of 6.10 (6.19) on the PHQ-8, and men (n = 195) had a lower score of 4.62 (5.28) (t = 2.75; P < 0.01). There was a significant main effect of depression, but not gender, on patients' adherence to diabetes medications in that those who were categorized as depressed had significantly worse adherence to diabetes medications (F = 4.82; P = 0.03).Additionally, there was a significant “gender x depression” interaction effect on adherence (F = 5.93; P = 0.01). Men with depression had mean adherence scores that indicated more nonadherence than did men without depression (9.44 [3.45] vs 7.47 [2.50], respectively), but adherence varied little between women with depression and women without depression (7.83 [2.69] vs 7.55 [2.58], respectively).Conclusions: The association between depression and medication adherence appears to be stronger in men than in women. Clinicians should be cognizant of the potential effect of depression on self-care for diabetes, particularly in men with depressive symptoms.     

Gender differences in psychosocial responses to lung cancer

Background: Although biologically based sex differences in the smoking patterns, epidemiology, biomedical markers, and survival rates associated with lung cancer are well documented, examinations of psychosocial gender differences are scarce.Objective: This cross-sectional study examined gender differences in psychosocial factors that are important in the medical management of lung cancer.Methods: A convenience sample of patients who were attending a multidisciplinary lung cancer treatment center (Markey Cancer Center, Lexington, Kentucky) were invited to complete a psychosocial needs assessment. Eligibility criteria included primary diagnosis of lung cancer, age ≥18 years, and being cognitively intact. Measures focused on psychosocial resources, treatment decision-making, social consequences of treatments, and treatment outcomes. Data were collected between the fall of 2005 and the summer of 2006.Results: A total of 47 women and 53 men (mean [SD] age, 62.81 [12.01] years; 95% white) completed the needs assessment. Gender was not found to be associated with demographic characteristics, time until diagnosis, treatment, or survival rate. Smoking histories differed significantly in the proportion of women and men who smoked or were former smokers (P = 0.01) as well as the age when they began to smoke (P = 0.02). There were no significant gender differences in social support networks, general coping, information needs, treatment decision satisfaction, functional health, life satisfaction, financial impact, or service needs. However, significant gender differences did indicate that women favored spiritual practices (P = 0.02) and religious coping (P = 0.04), and were more likely to endorse having a life mission (P = 0.03) and being part of a divine plan (P = 0.01).Conclusions: Previous research has found that religiousness and spirituality improved depressive symptoms and may ease end-of-life despair. In the present study of patients with lung cancer, gender differences in religiousness and spirituality suggest that this may be especially true for women, and that interventions should be directed toward their religious practices and coping.