Diagnosing occupational asthma: how, how much, how far?

Diagnosing occupational asthma is still a challenge because it is based on a stepwise approach in which the depth of investigative means may vary depending on resources. The authors herewith review the existing investigative means from the approach of outlining controversies and queries. There is no validated clinical questionnaire for diagnosing occupational asthma. Immunological investigation is limited by the lack of standardised extracts for skin-prick testing and specific immunoglobulin E assessments. Criteria for interpretation of changes in peak expiratory flow rates and bronchial responsiveness to pharmacological agents are still open to discussion. It is worth improving the methodology of specific inhalation challenges, either in the laboratory or in the workplace, to facilitate more extensive use of these tests. Validation of new means that assess airway inflammation, such as exhaled nitric oxide and induced sputum, needs to be performed. There is a need to increase the use of these diagnostic tests because the diagnosis is still too often based on "clinical impression".     

Gastroesophageal reflux disease in intellectually disabled individuals: how often, how serious, how manageable?

Gastroesophageal reflux disease (GERD) is an important and frequently occurring problem among intellectually disabled individuals (IDI). Early suspicion and recognition of the presence of GERD in IDI is the cornerstone of adequate management of these patients. The prevalence of GERD among institutionalized IDI with an IQ < 50 is about 50%, with 70% of these reflux patients having endoscopically established reflux esophagitis. In case of symptoms as hematemesis, rumination, or dental erosions, there is an increased risk for GERD. GERD has also been shown to be associated with cerebral palsy, an IQ < 35, scoliosis, and the use of anticonvulsant drugs or benzodiazepines. To establish the diagnosis, 24-h pH measurement or endoscopy should be used in all those intellectually disabled individuals in whom GERD clinically is suspected. The efficacy of proton-pump inhibitors (PPIs) in IDI with GERD is indisputable. In IDI, adults as well as children, PPIs are highly effective, independent of the severity of esophagitis. Marked improvement of symptoms and quality of life can be noticed after medical treatment, thereby decreasing the need for surgery in this complicated group of patients.     

Fat distribution and storage: how much, where, and how?

Obesity does not necessarily imply disease and similarly obese individuals may manifest obesity-related morbidity or seemingly be in reasonably good health. Recent studies have shown that patterns of lipid partitioning are a major determinant of the metabolic profile and not just obesity per se. The underlying mechanisms and clinical relevance of lipid deposition in the visceral compartment and in insulin-sensitive tissues are described. Increased intramyocellular lipid deposition impairs the insulin signal transduction pathway and is associated with insulin resistance. Increased hepatic lipid deposition is similarly associated with the majority of the components of the insulin resistance syndrome. The roles of increased circulating fatty acids in conditions of insulin resistance and the typical pro-inflammatory milieu of specific obesity patterns are provided. Insights into the patterns of lipid storage within the cell are provided along with their relation to changes in insulin sensitivity and weight loss.     

Treating undifferentiated arthritis. What, when, how and how long?

With the establishment of early arthritis clinics, patients can now be increasingly attended early in the course of their disease. This means that a significant proportion of these patients cannot be classified into a specific diagnosis using the traditional American College of Rheumatology (ACR) classification criteria. In these patients with undifferentiated arthritis (UA), even more important than assigning a diagnosis is the need to distinguish between patients who will develop a persistent and/or erosive disease and will be candidates for prompt treatment with disease-modifying antirheumatic drugs (DMARD), and patients in whom the disease is self limiting. Serologic markers in combination with clinical features at presentation, integrated into predictive models, are the tools currently available to the clinician for identifying these patients. Several studies have demonstrated the advantages of early treatment in UA.     

Clopidogrel in acute coronary syndrome: when, how much, how long?

Summary An important part of the therapy management of acute coronary syndrome (ACS) consists of antiplatelet drugs. Whereas the administration of acetylsalicylic acid (ASA) is well established, the guidelines recommend the additive use of clopidogrel in patients with ACS without persisting ST-elevation. Clopidogrel should be added to ASA as soon as possible in patients with a non-invasive treatment strategy and continued for more than 1 month (class 1A) and up to 9 months (class 1B). In patients for whom a percutaneous coronary intervention (PCI) is planned, an additional loading-dose of 300 mg clopidogrel should be given on top of ASA (100 mg).These recommendations are based on data recently published in the CURE and CREDO trials, which however should be critically discussed: In these trials, an absolute risk reduction of only 2% could be documented by additive use of clopidogrel. The combined endpoint of cardiovascular death, myocardial infarction and stroke is significantly reduced, but there was no improvement taken the individual endpoints alone. In additional, the data for duration of clopidogrel therapy were determined by taken the mean follow-up of these studies. The efficacy of the dual antiplatelet therapy should be discussed in the context of an increased frequency of major bleedings (in total 1%) and should be considered against a reasonable cost effective background.An adequate therapy with clopidogrel in patients presenting ACS should be confirmed by further trials. Until more detailed data are available, the guideline recommendations should be implemented based on of patients individual risk.     

Sex workers in Vietnam: how many, how risky?

Because of concerns for HIV risks and need to plan effective programs, we assessed the number and risks of sex workers in Nha Trang City, Vietnam. Sex workers were contacted in streets, beaches, bars, and restaurants, and a capture-recapture method was used to estimate their number. An estimated 444 women worked on the streets and beach ("direct" sex workers) and 486 worked in bars and restaurants or other facilities ("indirect" sex workers). Direct and indirect sex workers engaged in sex work primarily to support their families. Direct sex workers were older and were more at risk for HIV risk than were indirect sex workers. Direct sex workers had more clients, were less likely to report always using condoms (67% vs. 81%), more likely to report a prior sexually transmitted infection (19% vs. 16%), and more likely to have clients who inject drugs (16% vs. 13%). This assessment has implications for planning programs to reduce sex work and its risks in Vietnam and potentially other countries.     

Exercise and heart disease in women: why, how, and how much?

Despite a traditional view that cardiovascular disease primarily affects men, a growing body of information now recognizes that it is a disease that equally affects women and is the leading cause of morbidity and mortality in women in the United States. Both physical activity and physical fitness have been shown to have an inverse association with coronary heart disease and cardiovascular risk factors. Furthermore, physical inactivity is now recognized by the American Heart Association as an independent risk factor for coronary heart disease. However, national surveillance programs have reported that 1/4 of adults are currently sedentary, and 1/3 of women do not engage in any leisure-time physical activity. Regular exercise may significantly impact coronary heart disease in women, as some coronary risk factors have a stronger predictive value for coronary heart disease in women as compared with men. Recent studies have shown that women who exercise regularly are less likely to develop diabetes mellitus; exercise may reduce blood pressure and produce improvements in lipid profiles. Conflicting data exist regarding the dose and intensity of exercise necessary to achieve significant health benefits; however, many reports demonstrate a reduced risk of mortality from cardiovascular diseases and from all causes with only moderate intensity physical activity. The Centers for Disease Control, American Heart Association, and American College of Sports Medicine recommend a regular pattern of physical activity of moderate intensity, which can be accumulated throughout the day and should be performed at least 3 to 5 days per week. In addition, the benefit of weight-bearing exercise should be underscored in women, because it plays an important role in the prevention and treatment of osteoporosis. Continued efforts are necessary to encourage the many American women who are currently inactive to make even modest increases in levels of physical activity to achieve substantial cardiovascular, as well as other, health benefits.     

Eukaryogenesis,how special really?

Eukaryogenesis is widely viewed as an improbable evolutionary transition uniquely affecting the evolution of life on this planet. However, scientific and popular rhetoric extolling this event as a singularity lacks rigorous evidential and statistical support. Here, we question several of the usual claims about the specialness of eukaryogenesis, focusing on both eukaryogenesis as a process and its outcome, the eukaryotic cell. We argue in favor of four ideas. First, the criteria by which we judge eukaryogenesis to have required a genuinely unlikely series of events 2 billion years in the making are being eroded by discoveries that fill in the gaps of the prokaryote:eukaryote “discontinuity.” Second, eukaryogenesis confronts evolutionary theory in ways not different from other evolutionary transitions in individuality; parallel systems can be found at several hierarchical levels. Third, identifying which of several complex cellular features confer on eukaryotes a putative richer evolutionary potential remains an area of speculation: various keys to success have been proposed and rejected over the five-decade history of research in this area. Fourth, and perhaps most importantly, it is difficult and may be impossible to eliminate eukaryocentric bias from the measures by which eukaryotes as a whole are judged to have achieved greater success than prokaryotes as a whole. Overall, we question whether premises of existing theories about the uniqueness of eukaryogenesis and the greater evolutionary potential of eukaryotes have been objectively formulated and whether, despite widespread acceptance that eukaryogenesis was “special,” any such notion has more than rhetorical value.     

Perspectives of chromo and magnifying endoscopy: how, how much, when, and whom should we stain?

The goal of every routine endoscopy in the gut is the early diagnosis of malignant and premalignant changes of the mucosa. Chromo- and magnifying endoscopes are exciting new tools and offer detailed analysis of the colonic mucosal surface and pit pattern architecture. This review summarizes recent advances in endoscopic characterization of colorectal lesions using magnification endoscopy and chromoendoscopy. Surface analysis of the colon using chromoendoscopy allows a prediction between non-neoplastic and neoplastic lesions with high specificity. The precise delineation of the borders and a more detailed macroscopic analysis of the lesions are further advantages. In particular, flat adenomas and early depressed cancers are now more frequently recognized in western countries suggesting that significant lesions were overlooked by conventional endoscopy in the past. Furthermore, chromoendoscopy can be used in a targeted fashion to screen for sporadic adenomas. Finally, in surveillance colonoscopy, patients with long-standing ulcerative colitis have a valuable benefit if targeted biopsies are performed to detect intraepithelial neoplasias after pan-chromoendoscopy with methylene blue. Although there is a long learning curve, chromoendoscopy should thus belong to every endoscopists armamentarium. However, detailed knowledge about the technique, dyes, and specific staining patterns are mandatory before the yield of screening or surveillance colonoscopy can be increased. The new detailed images seen with magnifying chromoendoscopy are unequivocally the beginning of a new era where new optical developments will allow a unique look on cellular structures.     

Insulin secretagogues: Who,what, when,and how?

Sulfonylurea compounds were the first available oral antidiabetic agents and they remain an important tool in our quest for optimal glycemic control. The more recent introduction of meglitinides offers an approach to short-term insulin release with minimal hypoglycemic risk during fasting periods. Published trials suggest that individuals with a hemoglobin A_1c above 8.5% are unlikely to reach currently recommended targets (6.5% to 7%) without the use of one of these insulin secretagogues. Starting and probable maximally effective doses for glimepiride are 1 to 2 mg initially and 4 mg thereafter. For glyburide and glipizide, these are 2.5 to 5 mg initially, and 10 mg effective at a maximum. The large majority of the effect can be seen within a week, making them very attractive when rapid lowering of glucose is needed. An understanding of the principles will facilitate more effective use of initial and combination therapy.     

Screening for hepatocellular carcinoma: Why,when, how?

Hepatocellular carcinoma (HCC) is a major public health concern in many areas of the world, and its incidence is increasing in the United States and other countries. Screening for HCC in patients with cirrhosis has been advocated to identify those with small lesions who would benefit from transplantation or surgical resection. Despite these recommendations, several issues regarding screening remain controversial. No randomized, controlled trials have confirmed that surveillance for HCC reduces disease-specific mortality. In addition, the most appropriate screening test and optimal screening interval have not yet been defined. Clearly, these unresolved questions have a major impact on the cost-effectiveness of a screening program either at the population or the clinic level. A few studies, however, have suggested that screening may be cost-effective because a minor survival benefit could result in a cost that is acceptable to decision makers.     

Anxiety and depression in cardiology patients: how to diagnose, how to treat?

IMPORTANCE: Anxiety and depression are frequent problems in patients with heart diseases. Prevalences vary between 15 and 50%, depending on diagnostic criteria as well as on sociodemographic and medical patient characteristics. During the last 10-15 years, a large number of studies have shown that anxiety and depression strongly affect overall well-being, cardiac and non-specific symptom reporting and overall quality of life. This leads to increased health care utilization, early retirement and imposes a financial burden on individuals and social security systems. In addition, anxious and especially depressed patients with heart disease tend to exhibit unhealthy illness behavior, low compliance and suboptimal risk factor control. Together with the known physiological effects of negative affect on cardiac autonomic balance, inflammation and platelet function, these behavioral mechanisms may lead to the frequently observed increase of cardiac event and mortality rates in depressed patients wit coronary artery disease. DIAGNOSIS: Despite their clinical relevance and unsatisfactory spontaneous remission rate, anxiety and depression still go unrecognized and undertreated in most cardiac patients. Case-identification can be improved by a graded approach. In the first step, symptoms of anxiety and depression should explicitly be asked for as part of a routine cardiological work-up. As an adjunct, validated self-rating questionnaires can be used for screening purposes. Patients screened positive should receive a thorough diagnostic interview and a criteria-based diagnosis. TREATMENT: Once a diagnosis has been obtained, several treatment options are available: In less severe cases (minor depression or adjustment disorders), supportive care by primary care physicians or cardiologists may be sufficient. Patients with major depression or panic disorder should receive structured psychotherapy and/or antidepressant medication. Exercise training can also improve symptoms of anxiety and depression. Although both psychotherapy and antidepressants, especially if integrated in a concept of comprehensive cardiac care, can be expected to result in marked subjective benefit for the majority of patients, the impact of these treatments on cardiac event and mortality rates still needs to be determined.     

Liver biopsy: When, how, by whom, and where?

Liver biopsy remains an important diagnostic tool in the management of liver disease. Complications, though infrequent, are potentially disastrous. Risks and discomfort can be minimized with good technique, although prospective data to prove the superiority of one method over another are often lacking. Image direction is preferred in all cases, as is a transjugular approach when bleeding risks are judged to be high. Bleeding is essentially a random event. Outpatient liver biopsy is appropriate in almost every instance if immediate hospitalization facilities are available. It should be more widely practiced. Liver biopsies should only be done if, after thoughtful assessment, benefits are thought to exceed risks.