Malaria vaccines: a toy for travelers or a tool for eradication?

The demonstration of efficacy of two candidate malaria vaccines in children living in malaria-endemic areas, namely RTS,S from the circumsporozoite protein that reduced infection and clinical malaria in Mozambique, and an asexual blood-stage vaccine combining MSP1/MSP2/RESA that reduced parasite density in Papua New Guinea, allows one to believe that a malaria vaccine will be available for the fight against malaria in the next decade. Even if long-lasting impregnated bednets and indoor residual spraying have proven to be effective in reducing malaria transmission, these interventions may not be sufficient in the long-run since they rely on too few compounds and are, thus, vulnerable to the emergence of resistance. New tools, such as malaria vaccines, may, therefore, provide an added value to achieve the goal of local elimination and subsequent eradication of malaria. A promising candidate for that purpose would be a highly efficacious multicomponent vaccine that includes at least a sexual-stage antigen, the appropriate initial setting would be an area with low endemicity and limited population exchange, and the most suitable mode of delivery would be mass vaccination. For nonimmune populations, such as travelers visiting malaria-endemic areas, the usefulness of the first generation of malaria vaccine(s) will be limited, since the level of protection that is foreseen is unlikely to achieve that of malaria chemoprophylaxis. Only long-term travelers, expatriates and soldiers might realistically benefit from a pre-erythrocytic and/or blood-stage vaccine with an intermediate level of efficacy.     

Medical education: creating physicians or medical technicians?

The 20th century witnessed phenomenal growth in scientific medical knowledge and technology, enabling physicians to more accurately diagnose and effectively treat a wide range of diseases. However, these advances led to longer and more complex training periods for physicians and increasing specialization and dependence on the new technology. An adverse outcome of these changes has been the development of many physicians who are less able to communicate with their patients and deal with them in a humanistic and personally caring manner; ie, the development of finely trained medical technologists as opposed to caring physicians. Their behavior and their blind trust in science and technology without understanding the patients in whom illness occurs often leads to making incorrect, incomplete, or inappropriate diagnoses or to unnecessary failures of treatment. It also results in excessive costs, hazardous procedures, and ill will from patients. Unfortunately, such technologically oriented physicians are often the primary role models for students. The best hope for a remedy to the problem lies in recognizing that it exists, understanding its causes, and modifying medical education accordingly. Providing students with good role models and some rudimentary techniques can lead to significant gains, but sophisticated programs have been designed only in some schools.     

Evaluation: salvation or nemesis of medical informatics?

The currently prevailing paradigms of evaluation in medical/health informatics are reviewed. Some problems with application of the objectivist approach to the evaluation of real-rather than simulated-(health) information systems are identified. The rigorous application of the objectivist approach, which was developed for laboratory experiments, is difficult to adapt to the evaluation of information systems in a practical real-world environment because such systems tend to be complex, changing rapidly over time, and often existing in a variety of variants. Practical and epistemological reasons for the consequent shortcomings of the objectivist approach are detailed. It is argued that insistence on the application of the objectivist principles to real information systems may hamper rather than advance insights and progress because of this. Alternatives in the form of the subjectivist approach and extensions to both the objectivist and subjectivist approaches that circumvent the identified problems are summarized. The need to include systems engineering approaches in, and to further extend, the evaluation methodology is pointed out.     

CYP46: a risk factor for Alzheimer's disease or a coincidence?

Excess cholesterol is removed from the brain via hydroxylation mediated by cholesterol 24S-hydroxylase (CYP46). Although serum and cerebrospinal fluid (CSF) concentrations of 24S-hydroxycholesterol are altered during the progress of Alzheimer's disease, studies carried out to date in different populations on the association of CYP46 gene polymorphisms and risk of AD have been inconclusive. In this report, we analyzed CYP46 polymorphisms in 215 Polish AD cases and 173 healthy individuals. A fragment of CYP46 intron 2 was amplified by PCR reaction and sequenced. We discovered a new single nucleotide substitution in CYP46 intron 2, but found no difference in particular genotype or allele frequencies between AD patients and controls. However, the GG genotype of the known rs754203 polymorphic site might be a risk factor for AD, especially in APOE varepsilon4 carriers. Interestingly, in AD patients the rs754203 G allele was more frequent in males than in females. However, considering the extreme divergence of results obtained by different authors, a clear connection between the CYP46 gene and AD is questionable.     

Anatomy teaching for medical undergraduates: general practice as a guideline? The brain

Basic science teaching, particularly the teaching of gross anatomy, is at present a highly controversial topic. How much and what kind of anatomy should be taught to medical undergraduates nowadays? In conducting the present study we based our proposals on the criterion of general medical relevance. Therefore, we sent an anatomical questionnaire to a sample of Swiss general practitioners. Here, we present the results derived from questions on the human brain, discussing them in connection with the other organs so far investigated. The results obtained suggest that a common body of anatomical knowledge appropriate for the field of general medical practice does in fact exist. We believe that this basic stock can serve as a guideline for decision makers involved in the development of curricula, which can be fitted into the time frame available for anatomy teaching today while still guaranteeing a sound level of competence required for general practice of medicine. We also hope that this approach may serve as a model for the teaching of other basic sciences.     

Apoptosis or necrosis for tumor immunotherapy: what's in a name?

Here we discuss how the mechanisms by which tumor cells are killed in vivo by gene transfer affects their immunogenicity. Our own work has shown that necrotic cell death induces immunological activation signals which recruit, load, activate and mature appropriate subsets of antigen-presenting cells. In contrast, for apoptotic cell death to be immunogenic, signals additional to cell death alone must be provided within the milieu of the dying tumor. Our conclusion is that the immunogenicity of tumor killing is determined by a combination of factors, including the mechanism of killing, the levels of cell death, the local environment that exists within the dying tumor and, as a result, the nature of the immune/scavenger cells which are present at the time of antigen release. Knowledge of how these factors can influence the immune system and lead to the breaking of tolerance to tumor-associated antigens, can potentially be exploited in the design of effective immunotherapies for cancer using gene transfer.     

Everolimus,a promising medical therapy for coronary heart disease?

Coronary heart disease is mainly caused by atherosclerosis, which is a multifactotial and systemic disease. Lipid metabolism disorder and chronic inflammation are two well accepted mechanisms leading to atherosclerosis. The key initiating process in athrogenesis is lipid retention in subendothelium. Inflammatory activity plays an important role in the whole pathogenesis of atherosclerosis. Recent investigations have demonstrated that rapamycin reduces lipid retention by increasing adipose-tissue lipase activity and decreasing lipoprotein lipase activity. Rapamycin also reduce intracellular lipid accumulation in smooth muscle cells and macrophages. Since rapamycin is a definite immunosuppressive agent, and inflammatory process has been involved in atherosclerosis, the compound would have effect on the progression of atherosclerosis through reducing inflammatory activity. Moreover, rapamycin would protect plaque from rupture by selectively clearing macrophages without affecting vascular smooth muscle cells.     

Diagnostic classification in patients with suspected deep venous thrombosis: physicians' judgement or a decision rule?

Background

Clinical decision rules can aid in referral decisions for ultrasonography in patients suspected of having deep venous thrombosis (DVT), but physicians are not always convinced of their usefulness and rely on their own judgement.

Aim

To compare the performance of a clinical decision rule with the probability of DVT presence as estimated by GPs.

Design of study

Cross-sectional survey.

Setting

Primary care practices in The Netherlands.

Method

GPs (n = 300) estimated the probability of the presence of DVT (range 0–100%) and calculated the score for the clinical decision rule in 1028 consecutive patients with suspected DVT. The clinical decision rule uses a threshold of three points and so, for the GP estimates, thresholds were introduced at 10% and 20%. If scores were below these estimates, it was not considered necessary to refer patients for further examination. Differences between the clinical decision rule and the GP estimates were calculated; this is discrimination (c-statistic) and classification of patients.

Results

Data of 1002 patients were eligible for analysis. DVT was observed in 136 (14%) patients. Both the clinical decision rule and GP estimates had good discriminative power (c-statistic of 0.80 and 0.82 respectively). Fewer patients were referred when using the clinical decision rule compared with a referral decision based on GP estimates: 51% versus 79% and 65% (thresholds at 10% and 20% respectively). Both strategies missed a similar and low proportion of patients who did have DVT (range 1.4–2.0%).

Conclusion

In patients suspected of DVT both GP estimates and a clinical decision rule can safely discriminate in patients with and without DVT. However, fewer patients are referred for ultrasonography when GPs rely on a clinical decision rule to guide their decision making.     

Reform of medical education in Bosnia-Herzegovina: luxury or necessity?

We present the current status of medical education in Bosnia-Herzegovina to set the stage for the curriculum reform. Two principal questions are asked: is the reform necessary, and is it possible? In spite of the differences in size and tradition of medical schools in Bosnia and Herzegovina (BH), they have more features in common than not: all of them are under internal and external pressures for change and reform, which will eventually be inevitable. The history and strategy of reform in Heidelberg, Germany, and Vienna, Austria, are described and recommendations are made on the basis of their experience. The consensus on the need for reforms has to be reached by all parties involved, ie, faculty, administration, students, and the medical community. After that, the reform process must proceed according to the agreed timetable. The job should be delegated to a dedicated task force and work coordinated through the ongoing "Dictum" project, directed exclusively at reform of medical curricula in BH. The project is funded by a European Union TEMPUS program.     

Tissue pathology in undergraduate medical education: atrophy or evolution?

Changes are occurring in undergraduate medical curricula and there is limited published information about how contemporary tissue pathology is taught. The aim of this study was to collect information on this topic and to invite expert opinion about best teaching practice. A postal questionnaire survey of medical schools in the UK was performed, with a response rate of 23/28 schools (82%). The two most striking findings were the variation in teaching and learning strategies between schools and the spirit of the respondents, some relishing the challenges associated with reorganization and some thoroughly demoralized. The main concerns about pathology teaching were a feeling of lack of ownership of the content taught, an overall lack of visibility of tissue pathology in teaching and assessment, and staff shortages. Respondents valued the autopsy as an educational tool but were finding it increasingly difficult to provide. On the other hand, key opportunities for pathology teaching were highlighted through the questionnaire. The potential for developments in information technology and the possibility of creating national forums to develop core curricula and generate e-resources was recognized. The findings of this study will provide a milestone against which future change in pathology education can be measured.     

Talking medicine: a course in medical humanism--what do third-year medical students think?

OBJECTIVE: The early 1990s sparked an interest in organized medicine to reclaim and re-evaluate how it promotes professionalism among physicians. The American Board of Internal Medicine (ABIM) launched Project Professionalism as a means to define and evaluate professionalism as a component of clinical competence. The course "Talking Medicine" was developed to create a series of small-group discussions on humanism and professionalism where students can reflect on the process of becoming a physician and share personally or ethically difficult and rewarding cases with each other. We asked students to define these concepts and use these definitions to spark small-group discussion. DESCRIPTION: "Talking Medicine" is predicated on the belief that humanism and professionalism come to students and others through understanding a number of core concepts and relationships complemented by self-reflection. "Talking Medicine" offers a consistent (every other week for ten weeks) opportunity to share experiences in small groups (six to eight students), facilitated by two preceptors, in a format driven by students' experiences. Although the focus is on students' experiences, readings are provided on basic topics and contexts in humanism and professionalism (e.g., end-of-life care, mistakes, spirituality in medicine, and boundaries between patients and doctors). Also, at the beginning of each internal medicine clerkship we asked students to define humanism and professionalism anonymously on sheets of paper to be handed to the preceptors. DISCUSSION: "Talking Medicine" began in summer 2000. We hope to expand it to other institutions. We surveyed students and found 94% felt "very" or "somewhat" comfortable in the course. Seventy-three percent of students reported that the course increased their "connectedness" to classmates, and 61% favored its occurring during all rotations. Fifty-nine percent reported that their interest in caring for patients improved, and 53% reported their interest in internal medicine as a field improved. Answers to open-ended questions highlighted the importance of "Talking Medicine" as a forum to connect with others-both students and faculty. Despite this course's focus during an internal medicine clerkship, students see a broader definition of professionalism than the ABIM; the student's definitions were similar in many ways to the Group of Educational Affairs definition of professionalism. Third-year medical students focus more on tolerance of difference (e.g., race, socioeconomic status, and varying health beliefs), and the importance of collegiality and collaboration in the new environment of patient care. Their vantage point early in training allows them to look critically at the profession they are joining and view its shortcomings and strengths. Future work is needed that focuses on how these definitions change as students' progress through fourth year, into residency, and finally continuing medical education. Nevertheless, we suggest that "Talking Medicine" may be most effective in helping classmates connect to and learn from each other, thereby setting a foundation for changes in how they interact with patients.