Neuromelanin-containing neurons of the substantia nigra accumulate iron and aluminum in Parkinson's disease: a LAMMA study

The Laser Microprobe Mass Analyzer (LAMMA) is a sensitive instrument for identifying and localizing trace elements in tissue samples. Using LAMMA, we have examined melanin-containing neurons of the substantia nigra in patients with Parkinson's disease (PD) and controls. We found that iron significantly accumulates within neuromelanin granules of patients with PD compared to controls. Increased aluminum was found in the neuromelanin granules of 2 of 3 PD cases but in no controls. The accumulation of iron and aluminum, which are known to promote oxidant stress, may account for the selective degeneration of neuromelanin-containing neurons in PD.     

Irritable bowel syndrome: The role of psychosocial factors

The irritable bowel syndrome (IBS) is a very common disorder of intestinal function characterized by variable symptoms of abdominal pain, diarrhea, constipation and bloating. The spectrum of severity ranges from mild symptoms, not worthy of clinical attention, to intense and continuous symptoms associated with impaired health-related quality of life and high health care use. Psychosocial disturbance is commonly found among patients with irritable bowel, but until recently, its precise role in the disorder was uncertain. The data now suggest that irritable bowel is not a psychiatric disorder per se, but psychosocial factors including life stress, psychiatric comorbidity and abnormal illness behavior, among others, influence how the illness is experienced and acted upon. Patients with mild symptoms usually respond to education, reassurance, dietary modification and, when needed, antimotility agents. However, patients with more severe symptoms, who usually have greater psychosocial disturbance, will also require behavioral interventions, and possibly psychopharmacological agents. In sum, a graduated, multicomponent plan of care that includes dietary, behavioral and pharmacological treatments is recommended.     

Psychiatric morbidity in policemen and the effect of brief psychotherapeutic intervention — a pilot study

The level of psychiatric morbidity and perceived sources of stress among police officers were investigated using the General Health Questionnaire (GHQ) and a stress situation questionnaire, which were sent to 171 officers. Half of the responders were invited to attend group counselling sessions weekly for 12 weeks. Outcome measures studied were a second GHQ completed at the end of the treatment period and the amounts of sick leave taken in the 12-week period before, during and after the treatment period. The results were that 61 people returned the first GHQ of whom 59 were male and of whom 14 were classed as ‘cases’. Of the 31 assigned to the treatment group, 22 attended at least one session. Responses to the stress situation questionnaire and the content of counselling sessions tended to confirm the impression that internal aspects of the organization were viewed as prime sources of stress and dissatisfaction. There were no significant changes in GHQ score within or between groups, nor were there significant differences in the amount of sick leave taken. Nevertheless the sessions appeared to be valued and we conclude that this sort of intervention is at least feasible. We recommend that similar studies measure psychiatric morbidity during treatment and at follow-up, rather than immediately after finishing, when reactions to this termination are prominent.     

经阴道无张力吊带术治疗女性压力性尿失禁的体会

目的探讨经阴道无张力吊带术(TVT)治疗女性压力性尿失禁(SUI)的疗效及安全性。方法对2002年5月至2004年12月施行TVT的114例女性SUI患者资料进行回顾性研究。根据Stamey尿失禁分级系统评价TVT手术的有效性。术后较术前尿失禁等级评分改善2级或2级以上为显著改善,1级为改善,无改善甚至加重为无效。术后尿失禁等级为0~1级为完全控尿,2级为有效控尿,3~4级为无效。评估术前、术后的24h尿垫试验及尿动力学检查结果。并对并发症进行统计和分析。结果随访110例(96.5%),随访时间6~30个月。24h尿垫试验术前(38.3±10.4)g,术后(8.8±7.4)g;尿失禁症状评分从术前42.3±11.4,术后20.4±9.2;尿失禁等级评分显著改善者94例(85.5%),改善者12例(10.9%),无效者4例(3.6%)。术后完全控尿者89例(80.9%),有效控尿者14例(12.7%),无效者7例(6.4%)。术中发生膀胱穿孔2例(1.8%),出血14例(12.7%)。术后1个月内有排尿不畅者9例(8.2%),尿频、尿急者12例(10.9%),尿潴留者1例(0.9%);术后6个月后有耻骨上不适者8例(7.3%),排尿不尽者2例(1.8%),尿频、尿急者3例(2.7%)。1例反复尿潴留患者经保守治疗无效,最终将吊带切断。术后未出现吊带处阴道黏膜糜烂和明显盆腔血肿。结论TVT术是目前治疗女性SUI的一种有效、安全的微创手术。     

Anthracycline-induced cardiotoxicity: Overview of studies examining the roles of oxidative stress and free cellular iron

The risk of cardiotoxicity is the most serious drawback to the clinical usefulness of anthracycline antineoplastic antibiotics, which include doxorubicin (adriamycin), daunorubicin or epirubicin. Nevertheless, these compounds remain among the most widely used anticancer drugs. The molecular pathogenesis of anthracycline cardiotoxicity remains highly controversial, although the oxidative stress-based hypothesis involving intramyocardial production of reactive oxygen species (ROS) has gained the widest acceptance. Anthracyclines may promote the formation of ROS through redox cycling of their aglycones as well as their anthracycline-iron complexes. This proposed mechanism has become particularly popular in light of the high cardioprotective efficacy of dexrazoxane (ICRF-187). The mechanism of action of this drug has been attributed to its hydrolytic transformation into the iron-chelating metabolite ADR-925, which may act by displacing iron from anthracycline-iron complexes or by chelating free or loosely bound cellular iron, thus preventing site-specific iron-catalyzed ROS damage. However, during the last decade, calls for the critical reassessment of this “ROS and iron” hypothesis have emerged. Numerous antioxidants, although efficient in cellular or acute animal experiments, have failed to alleviate anthracycline cardiotoxicity in clinically relevant chronic animal models or clinical trials. In addition, studies with chelators that are stronger and more selective for iron than ADR-925 have also yielded negative or, at best, mixed outcomes. Hence, several lines of evidence suggest that mechanisms other than the traditionally emphasized “ROS and iron” hypothesis are involved in anthracycline-induced cardiotoxicity and that these alternative mechanisms may be better bases for designing approaches to achieve efficient and safe cardioprotection.     

Psychological well‐being and psychosocial work environment characteristics among emergency medical and nursing staff

The aim of this study was to determine if the effect of psychosocial work environment on psychological well‐being was different for doctors and nurses who work in emergency departments in Spain. A cross‐sectional survey was carried out among 945 emergency doctors and nurses staff from Spain. The outcome variable was the psychological well‐being measured by two dimensions of SF‐36 Health Survey (SF‐36) (mental health, vitality) and one dimension of Maslach's Burnout Inventory (emotional exhaustion). The explanatory variable was the psychosocial work environment evaluated according to Karasek and Johnson's demand‐control model that includes the dimensions of psychological demands, job control, supervisor social support and co‐workers' social support. The adjusted odds ratios and their 95 per cent confidence intervals were calculated by logistic regression. The prevalence of low vitality, bad mental health and high emotional exhaustion was higher among doctors than nurses. Exposure to high psychological demands increased the probability of low vitality, bad mental health and high emotional exhaustion among doctors and nurses. Low job control and low co‐workers' social support at work were associated with poor psychological well‐being only among doctors. Low job supervisors' social support increased the risk of bad mental health among doctors and of high emotional exhaustion among nurses. There is a different effect of psychosocial work environment on psychological well‐being between doctors and nurses. Copyright © 2007 John Wiley & Sons, Ltd.     

Mental stress-induced myocardial ischemia in coronary artery disease patients with left ventricular dysfunction

Background  Reduced left ventricular ejection fraction (LVEF) is a risk factor for poor outcomes in patients with coronary artery disease (CAD). Mental stress-induced myocardial ischemia (MSIMI) also identifies a subset of CAD patients at increased risk for future cardiovascular events. Susceptibility to MSIMI in patients with CAD and reduced LVEF is unknown. Methods and Results  We enrolled 182 patients (67 women) with a mean age of 64 years and a documented history of CAD in this study. Baseline resting ejection fraction was determined by use of technetium 99m sestamibi gated single photon emission computed tomography. Abnormal LVEF was defined as less than 45% for men and less than 50% for women (based on published norms for our software [Cedars-Sinai Medical Center]). All participants underwent mental stress testing with a public speaking task. Rest/stress myocardial perfusion single photon emission computed tomography was performed via conventional methodology. Images were visually compared for number and severity of perfusion defects by use of a scoring method from 0 to 4. A summed difference score was calculated as the difference between summed stress and rest scores. A score of greater than 3 was considered abnormal. MSIMI developed in 19% of patients with normal LVEF and 31% of those with reduced LVEF. There is no statistically significant difference between the two groups (P=.11). Conclusions  CAD patients with left ventricular dysfunction are equally susceptible to MSIMI as those with normal LVEF. This study was supported by grants HL 070265 and HL 072059 from the National Heart. Lung, and Blood Institute. This material is also the result of work supported by resources and with the use of facilities at the Department of Veterans. Affairs Medical Center, Gainesville, Fla.     

Effects of metyrapone on hypothalamic-pituitary-adrenal axis and sleep in women with post-traumatic stress disorder.

BACKGROUND: Metyrapone blocks cortisol synthesis which results in removal of negative feedback, a stimulation of hypothalamic corticotropin releasing factor (CRF) and a reduction in delta sleep. We previously reported a diminished delta sleep and hypothalamic-pituitary-adrenal (HPA) response to metyrapone in men with post-traumatic stress disorder (PTSD). In this study, we aimed to extend these findings to women. METHODS: Three nights of polysomnography were obtained in 17 women with PTSD and 16 controls. On day 3, metyrapone was administered throughout the day up until bedtime. Plasma adrenocorticotropic hormone (ACTH), cortisol, and 11-deoxycortisol were obtained the morning following sleep recordings the day before and after metyrapone administration. RESULTS: There were no significant between-group differences in hormone concentration and delta sleep at baseline. Relative to controls, women with PTSD had decreased ACTH and delta sleep responses to metyrapone. Decline in delta sleep was associated with the magnitude of increase in ACTH across groups. CONCLUSIONS: Similar to our previous findings in men, the ACTH and sleep electroencephalogram response to metyrapone is attenuated in women with PTSD. These results are consistent with a model of downregulation of CRF receptors in an environment of chronically increased CRF activity or with enhanced negative feedback regulation in PTSD.     

Perceived occupational stress,affective, and physical well-being among telecommunication employees in Greece

The present study examined four potential roles of work-related negative affectivity on the associations between self-reported occupational stress and physical well-being among telecommunication employees in Greece. Participants (764, predominantly male) completed a battery of self-report measures on perceived occupational stress, negative affectivity, and illness symptoms. In line with previous research, negative affectivity exerted a nuisance effect, by inflating the association between reported stressors and illness symptoms, and significantly predicted illness symptoms, over and above the effects of stressors. In addition, negative affectivity influenced reported illness symptom indirectly, through the effects of stressors, and moderated the relationship between interpersonal conflict at work and illness symptoms. The findings suggest that negative affectivity can largely explain and influence in different ways the associations between self-reported stress and physical strain. It is recommended that future studies of occupational stress should control for the effects of negative affectivity, and that health professionals should be cautious of its effects when interpreting relationships between self-reported occupational stress and physical well-being.