Assessing ethical problem solving by reasoning rather than decision making

Context The assessment of ethical problem solving in medicine has been controversial and challenging. The purposes of this study were: (i) to create a new instrument to measure doctors’ decisions on and reasoning approach towards resolving ethical problems; (ii) to evaluate the scores generated by the new instrument for their reliability and validity, and (iii) to compare doctors’ ethical reasoning abilities between countries and among medical students, residents and experts. Methods This study used 15 clinical vignettes and the think‐aloud method to identify the processes and components involved in ethical problem solving. Subjects included volunteer ethics experts, postgraduate Year 2 residents and pre‐clerkship medical students. The interview data were coded using the instruments of the decision score and Ethical Reasoning Inventory (ERI). The ERI assessed the quality of ethical reasoning for a particular case (Part I) and for an individual globally across all the vignettes (Part II). Results There were 17 Canadian and 32 Taiwanese subjects. Based on the Canadian standard, the decision scores between Taiwanese and Canadian subjects differed significantly, but made no discrimination among the three levels of expertise. Scores on the ERI Parts I and II, which reflect doctors’ reasoning quality, differed between countries and among different levels of expertise in Taiwan, providing evidence of construct validity. In addition, experts had a greater organised knowledge structure and considered more relevant variables in the process of arriving at ethical decisions than did residents or students. The reliability of ERI scores was 0.70–0.99 on Part I and 0.75–0.80 on Part II. Conclusions Expertise in solving ethical problems could not be differentiated by the decisions made, but could be differentiated according to the reasoning used to make those decisions. The difference between Taiwanese and Canadian experts suggests that cultural considerations come into play in the decisions that are made in the course of providing humane care to patients.     

Mycotic Aneurysm of the Thoracic Aorta Caused by Clostridium septicum

We describe a case of a 78-year-old man who presented with a mycotic aneurysm of the thoracic aorta caused by Clostridium septicum and underwent successful resection. There are only 3 cases of mycotic aneurysms caused by Clostridium septicum reported in the literature. Clostridium septicum infections have been shown to have a high association with gastrointestinal and hematologic malignancies. All patients with Clostridium septicum infections, therefore, require a search for gastrointestinal lesions, as they may represent a source of persistent bacteremia. This patient had no malignant lesions but did have multiple benign sigmoid polyps.     

Tolerance to self gangliosides is the major factor restricting the antibody response to lipopolysaccharide core oligosaccharides in Campylobacter jejuni strains associated with Guillain-Barré syndrome

Guillain-Barré syndrome following Campylobacter jejuni infection is frequently associated with anti-ganglioside autoantibodies mediated by molecular mimicry with ganglioside-like oligosaccharides on bacterial lipopolysaccharide (LPS). The regulation of antibody responses to these T-cell-independent antigens is poorly understood, and only a minority of Campylobacter-infected individuals develop anti-ganglioside antibodies. This study investigates the response to gangliosides and LPS in strains of mice by using a range of immunization strategies. In normal mice following intraperitoneal immunization, antibody responses to gangliosides and LPS are low level but can be enhanced by the antigen format or coadministration of protein to recruit T-cell help. Class switching from the predominant immunoglobulin M (IgM) response to IgG3 occurs at low levels, suggesting B1-cell involvement. Systemic immunization results in poor responses. In GalNAc transferase knockout mice that lack all complex gangliosides and instead express high levels of GM3 and GD3, generation of anti-ganglioside antibodies upon immunization with either complex gangliosides or ganglioside-mimicking LPS is greatly enhanced and exhibits class switching to T-cell-dependent IgG isotypes and immunological memory, indicating that tolerance to self gangliosides is a major regulatory factor. Responses to GD3 are suppressed in knockout mice compared with wild-type mice, in which responses to GD3 are induced specifically by GD3 and as a result of polyclonal B-cell activation by LPS. The anti-ganglioside response generated in response to LPS is also dependent on the epitope density of the ganglioside mimicked and can be further manipulated by providing secondary signals via lipid A and CD40 ligation.     

Levels of analysis in etiological research on schizophrenia

Etiological research spanning domains of inquiry as diverse as social psychology and molecular genetics has identified a number of potential factors that likely contribute to the development and clinical manifestation of schizophrenia. In this article, we first highlight the challenges inherent in developing cogent etiological models that represent both the diversity of suspected causal influences and their mechanisms of action. Then, using our own research program as a heuristic context, we present a general analytical framework for identifying and integrating multiple types of etiologic factors across different levels of analysis in the prediction of schizophrenia. In recognition of the myriad complexities of multifactorial causation, we argue that a multilevel causal perspective is required for the development and advancement of a fully nuanced theory of schizophrenia etiology and pathophysiology.     

Inflammatory Markers in Acute Myocardial Infarction Patients: Preliminary Evidence of a Prospective Association With Depressive Symptoms

Inflammatory activity has been associated with both coronary disease and depressive symptoms. We sought to determine whether inflammatory markers in myocardial infarction (MI) patients are prospectively associated with depressive symptomatology. Participants were a convenience sample of MI patients. Depressive symptoms were assessed soon after the MI and again 7 months postdischarge. Inflammatory markers examined were interleukin-6 (IL-6) and interleukin-1β. Results suggest no significant cross-sectional association between inflammatory markers and depressive symptoms at baseline. However, bivariate and multiple regression analyses revealed a significant positive prospective association between baseline IL-6 and depressive symptoms 7 months later ( β  = .57, p  < .01). The results suggest that temporal considerations are important in understanding relationships between inflammation and depressive symptoms following MI.     

Correlates of Intent to Seek Unnecessary Pap Tests Among Elderly Women

PURPOSE: Cervical cancer screening may be over-used by elderly women who might not benefit from the test. The purpose of this study was to examine the relative importance of objective factors (e.g. intact cervix) and subjective factors (e.g. patients' Pap-smear related beliefs/attitudes) as correlates of elderly women's intention to have a Pap smear. METHODS: This study was a secondary data analysis using a subset sample of the elderly women (>or=65 years) who participated in the Texas Tech 5000 Survey Wave 4, a cross-sectional phone interview study conducted in 2002. Intent to have a Pap test, previous gynecologic history, and beliefs/attitudes related to Pap tests were measured. chi2 tests and logistic regression were conducted. RESULTS: Among the 1,044 women in the analytical sample, 70.2% (733) reported intending to have a Pap smear test within the next 2 years. About 77% (449/582) of the women who had not undergone a hysterectomy reported the intend to have a Pap smear, whereas 62% (284/462) of the women who had undergone a hysterectomy reported the same intent (chi 2 = 30.26; df = 1; p = .000). Among women who had undergone a hysterectomy, having received a Pap smear within the past 2 years (odds ratio OR, 21.32; 95% confidence interval [CI], 11.52-39.47), perceiving that their doctors might feel having the test is a good idea (OR, 7.14; 95% CI, 3.15-16.19), and insurance covering the test (OR, 2.21; 95% CI, 1.18-4.15) were positive correlates of intent to have a Pap test. Among women who had not undergone a hysterectomy, previous Pap smear history (OR, 19.28; 95% CI, 10.15-37.10), perceived doctor's opinion (OR, 5.39; 95% CI, 2.38-12.19), perceived pain of the test (OR, 0.52; 95% CI, .28-.99), perceived importance (OR, 4.00; 95% CI, 1.32-12.10), and perceived risk of developing cervical cancer (OR, 4.27; 95% CI, 1.27-14.33) were correlates. CONCLUSIONS: Public health educational messages intended to increase appropriate use of Pap screening should include factual information about risk factors such as age and possession of an intact cervix. Other messages intended to reduce inappropriate use of Pap screening should be directed at physicians, since many elderly women intend to inappropriately seek Pap tests based on erroneous beliefs/attitudes.     

Atrazine-induced aromatase expression is SF-1 dependent: implications for endocrine disruption in wildlife and reproductive cancers in humans

BACKGROUND: Atrazine is a potent endocrine disruptor that increases aromatase expression in some human cancer cell lines. The mechanism involves the inhibition of phosphodiesterase and subsequent elevation of cAMP. METHODS: We compared steroidogenic factor 1 (SF-1) expression in atrazine responsive and non-responsive cell lines and transfected SF-1 into nonresponsive cell lines to assess SF-1's role in atrazine-induced aromatase. We used a luciferase reporter driven by the SF-1-dependent aromatase promoter (ArPII) to examine activation of this promoter by atrazine and the related simazine. We mutated the SF-1 binding site to confirm the role of SF-1. We also examined effects of 55 other chemicals. Finally, we examined the ability of atrazine and simazine to bind to SF-1 and enhance SF-1 binding to ArPII. RESULTS: Atrazine-responsive adrenal carcinoma cells (H295R) expressed 54 times more SF-1 than nonresponsive ovarian granulosa KGN cells. Exogenous SF-1 conveyed atrazine-responsiveness to otherwise nonresponsive KGN and NIH/3T3 cells. Atrazine induced binding of SF-1 to chromatin and mutation of the SF-1 binding site in ArPII eliminated SF-1 binding and atrazine-responsiveness in H295R cells. Out of 55 chemicals examined, only atrazine, simazine, and benzopyrene induced luciferase via ArPII. Atrazine bound directly to SF-1, showing that atrazine is a ligand for this "orphan" receptor. CONCLUSION: The current findings are consistent with atrazine's endocrine-disrupting effects in fish, amphibians, and reptiles; the induction of mammary and prostate cancer in laboratory rodents; and correlations between atrazine and similar reproductive cancers in humans. This study highlights the importance of atrazine as a risk factor in endocrine disruption in wildlife and reproductive cancers in laboratory rodents and humans.