Cutaneous hyperpigmentation induced by omeprazole mimicking ashy dermatosis

BACKGROUND: Omeprazole has been associated with multiple adverse effects including skin reactions but, to date, cutaneous hyperpigmentation has not been described as an adverse effect of this drug. OBSERVATIONS: We describe a case of a 52-year-old Caucasian woman who developed skin hyperpigmentation in the upper trunk, mimicking ashy dermatosis, 2 months after initiating omeprazole treatment. Histopathologic examination of a skin biopsy taken from a pigmented macule showed dermal macrophages containing golden-brown granules, which also displayed a sulphur peak on energy-dispersive X-ray microanalysis. High-performance liquid chromatography (HPLC) and mass spectrometry were also performed on the drug and on a biopsy specimen revealing the same chromatograms as well as the same mass spectra. CONCLUSIONS: According to our results, omeprazole itself may induce cutaneous pigmentation and, to our knowledge, this is the first report of this finding.     

The relationship between psychosocial work characteristics and fatigue and psychological distress

OBJECTIVES: To examine the associations between psychosocial work characteristics and fatigue in employees in the Maastricht Cohort Study. A second objective was to compare the relationships for fatigue versus psychological distress with these psychosocial work characteristics. METHODS: The design was cross-sectional and included 11,020 employees who responded to the self-administered baseline questionnaire of the Maastricht Cohort Study. Fatigue was measured with the Checklist Individual Strength, a 20-item self-report instrument. Psychological distress was measured with the 12-item version of the General Health Questionnaire. Psychosocial work characteristics comprised: psychological demands, decision latitude, and social support at work as measured by the Job Content Questionnaire, as well as emotional demands at work, physical demands at work, job insecurity, and conflict with supervisor/co-worker, which were assessed with items from existing Dutch questionnaires. RESULTS: Low decision latitude and low social support at work were associated with fatigue in both men and women. Associations were also found between emotional demands at work, job insecurity, physical demands and conflict with supervisor and fatigue in men; and high psychological demands and fatigue in women. As regards psychological distress, there was no association with low decision latitude, but strong associations with emotional demands and conflict with supervisor in both genders. CONCLUSIONS: The study provides strong support for associations between psychosocial work characteristics and fatigue in men and women, even after adjustment for psychological distress. Moreover, it suggests some differential effects of psychosocial work characteristics on fatigue and psychological distress.     

Myocardial reperfusion injury and oxidative stress: Therapeutic opportunities

Acute myocardial infarction(AMI) is the leading cause of death worldwide. Its associated mortality, morbidity and complications have significantly decreased with the development of interventional cardiology and percutaneous coronary angioplasty(PCA) treatment, which quick-ly and effectively restore the blood flow to the area previously subjected to ischemia. Paradoxi-cally, the restoration of blood flow to the ischemic zone leads to a massive production of reactive oxygen species(ROS) which generate rapid and severe damage to biomolecules, generating a phenomenon called myocardial reperfusion injury(MRI). In the clinical setting, MRI is associated with multiple complications such as lethal reperfusion, no-reflow, myocardial stunning, and reperfusion arrhythmias. Despite significant advances in the understanding of the mechanisms accounting for the myocardial ischemia reperfusion injury, it remains an unsolved problem. Although promising results have been obtained in experimental studies(mainly in animal models), these benefits have not been translated into clinical settings. Thus, clinical trials have failed to find benefits from any therapy to prevent MRI. There is major evidence with respect to the contribution of oxidative stress to MRI in cardiovascular diseases. The lack- of consistency between basic studies and clinical trials is not solely based on the diversity inherent in epidemiology but is also a result of the methodological weak-nesses of some studies. It is quite possible that pharmacological issues, such as doses, active ingredients, bioavailability, routes of administration, co-therapies, startup time of the drug intervention,and its continuity may also have some responsibility for the lack- of consistency between different studies. Furthermore, the administration of high ascorbate doses prior to reperfusion appears to be a safe and rational therapy against the development of oxidative damage associated with myocardial reperfusion. In addition, the association with N-acetylcysteine(a glutathione donor) and deferoxamine(an iron chelator) could improve the antioxidant cardioprotection by ascorbate, mak-ing it even more effective in preventing myocardial reperfusion damage associated with PCA following AMI.     

Do sequence variants in the major non-coding region of the mitochondrial genome influence mitochondrial mutations associated with disease?

Several different mutations in human mitochondrial DNA (mtDNA) have been associated with disease, but their origins and the basis of the wide phenotypic variability remain to be elucidated. We initially investigated three patients with heteroplasmic disease associated mutations of mtDNA for the presence of cis mutations in the major non- coding region that might influence their origins or pathology. A T --> C transition at nt 16 189 previously identified in one patient with the 3243 G:C mutation was associated with heteroplasmic length variation. Identical length variation was found in patient-derived cybrid lines containing 0-97.5% 3243 G:C. Similarly, heteroplasmic length variation was demonstrated in 2/6 other probands with both the 3243 mutation and the 16,189 polymorphism. The distribution of length variants in probands and in asymptomatic family members was identical in all cases. Thus length variation appears to be independent of the level of 3243 mutant mtDNA and hence probably arose within both 3243 G:C and 3243 A:T mtDNAs. We suggest that the 16,189 polymorphism reflects a predisposition to the formation or fixation of several different mutations in mitochondrial tRNA-LeuUUR.      

Primary Sclerosing Cholangitis: A Clinical Review

Primary sclerosing cholangitis (PSC) is a cholestatic liver disease characterized by fibro-obliterative inflammation of the entire biliary tree. It is a slowly progressive disease with an undulating course, resulting in terminal biliary cirrhosis after a median period of about 12 years after diagnosis. The etiology of the disease is unknown and there is no effective therapy that can halt disease progression. Around 8% of PSC patients develop cholangiocarcinoma, which, by the time it is diagnosed, cannot be treated curatively. The purpose of this article is to review the current knowledge about primary sclerosing cholangitis and to speculate on future strategies to address the issues of etiology and therapy.     

1—溴丙烷工厂工人健康状况调查及接触生物标记物的研究

目的 分析1-溴丙烷毒性并评价其危险度，探讨适宜的接触生物标记物，方法 对37名工人进行问卷调查。血液学指标和血生化指标的测定。包括垂体激素和性激素测定。以该工厂工人为接触组，食品厂工人为对照组，比较两组间的血浆，脶酸激酶（CK）活性和血浆肌酸激酶M亚基（CK-M）。尿中1-溴丙烷用气相色谱仪检测，个体暴露蓄积水平用个体采样器估测。结果 接触组工人出现眼，鼻，口腔，喉的粘膜刺激症状。部分工人出现眩晕，可能是神经系统的反应。结论 接触1-溴丙烷引起的主诉症状提示它能刺激上呼吸道粘膜，在约100mg/m^3浓度水平可影响中枢神经系统，尿1-溴丙烷浓度有望成为接触的生物标记物。