Dealing with the long-term social implications of research.

Biomedical and behavioral research may affect strongly held social values and thereby create significant controversy over whether such research should be permitted in the first place. Institutional review boards (IRBs) responsible for protecting the rights and welfare of participants in research are sometimes faced with review of protocols that have significant implications for social policy and the potential for negative social consequences. Although IRB members often raise concerns about potential long-term social implications in protocol review, federal regulations strongly discourage IRBs from considering them in their decisions. Yet IRBs often do consider the social implications of research protocols and sometimes create significant delays in initiating or even prevent such research. The social implications of research are important topics for public scrutiny and professional discussion. This article examines the reasons that the federal regulations preclude IRBs from assessing the social risks of research, and examines alternative approaches that have been used with varying success by national advisory groups to provide such guidance. The article concludes with recommendations for characteristics of a national advisory group that could successfully fulfill this need, including sustainability, independence, diverse and relevant expertise, and public transparency.

Historical perspective and clinical implications of the Pelger-Hüet cell.

The unique historical aspects of Pelger and Huet's discovery of the Pelger-Huet cell highlight the diagnostic challenge that this morphologic finding presents to the physician. Making the diagnosis of the benign autosomal dominant anomaly is complicated by the morphologically similar pseudo-Pelger-Huet cell, which can signify underlying myeloid dsyplasia. This article relates the history of the Pelger-Huet anomaly as well as describes the clinical significance and diagnostic workup for the finding of a Pelger-Huet cell on peripheral smear.

Managing incidental findings in human subjects research: analysis and recommendations.

No consensus yet exists on how to handle incidental findings (IFs) in human subjects research. Yet empirical studies document IFs in a wide range of research studies, where IFs are findings beyond the aims of the study that are of potential health or reproductive importance to the individual research participant. This paper reports recommendations of a two-year project group funded by NIH to study how to manage IFs in genetic and genomic research, as well as imaging research. We conclude that researchers have an obligation to address the possibility of discovering IFs in their protocol and communications with the IRB, and in their consent forms and communications with research participants. Researchers should establish a pathway for handling IFs and communicate that to the IRB and research participants. We recommend a pathway and categorize IFs into those that must be disclosed to research participants, those that may be disclosed, and those that should not be disclosed.

Lepromatous leprosy masquerading as acute sarcoidosis: a case report and literature review.

Leprosy is uncommon in North America. Because it has a prolonged incubation period and can masquerade with a variety of manifestations, many patients with leprosy experience a significant delay in diagnosis and treatment. Lepra reactions are of 2 types: reversal (type 1) and erythema nodosum leprosum (ENL) (type 2). Type 1 or reversal reactions represent an increase in cell-mediated immunity, whereas type 2 or ENL is caused by antigen-antibody complex formation and deposition after antigen release from dying lepra bacilli. This article describes the diagnostic challenges presented by a Minnesota patient eventually found to have lepromatous leprosy. That challenge was compounded by the fact that the clinical scenario closely mimicked connective tissue/immune complex disease and by the fact that the patient presented in a location where the incidence and prevalence of leprosy is extremely low.

Postoperative severe microangiopathic hemolytic anemia associated with a giant hepatic cavernous hemangioma.

Complications related to liver hemangioma are rare. We herein describe the case of a patient with three giant cavernous hemangiomas of the liver, of which two were resected for symptoms. A significant microangiopathic hemolytic anemia occurred in the early postoperative period, leading to acute renal failure and necessitating blood transfusions. The systematic evaluation of hemolytic processes in the postoperative patient is described. Surgeons should be aware of the potential for hemolytic complications after major surgery when giant hepatic hemangiomas are present.

"Special scrutiny": a targeted form of research protocol review.

Research participants require ongoing protection of the kind already established in law and regulation. However, "special scrutiny" for certain types of research is also needed. Three criteria for special scrutiny are 1) research that involves initial experiences of translating new scientific advances into humans, especially when the intervention is novel, irreversible, or both; 2) research with a known or credible risk for significant harm (death or serious disability are the clearest examples) to research participants as a consequence of the experimental intervention and with no potential for offsetting direct medical benefit; or 3) research with a protocol that raises ethical questions about research design or implementation for which there is no consensus. Special scrutiny recognizes that not all research protocols are equally ethically challenging and aims to provide appropriate protection for all research participants.

Oversight of human participants research: identifying problems to evaluate reform proposals.

The oversight of research involving human participants is widely believed to be inadequate. The U.S. Congress, national commissions, the Department of Health and Human Services, the Institute of Medicine, numerous professional societies, and others are proposing remedies based on the assumption that the main problems are researchers' conflict of interest, lack of institutional review board (IRB) resources, and the volume and complexity of clinical research. Developing appropriate reform proposals requires carefully delineating the problems of the current system to know what reforms are needed. To stimulate a more informed and meaningful debate, we delineate 15 current problems into 3 broad categories. First, structural problems encompass 8 specific problems related to the way the research oversight system is organized. Second, procedural problems constitute 5 specific problems related to the operations of IRB review. Finally, performance assessment problems include 2 problems related to absence of systematic assessment of the outcomes of the oversight system. We critically assess proposed reforms, such as accreditation and central IRBs, according to how well they address these 15 problems. None of the reforms addresses all 15 problems. Indeed, most focus on the procedural problems, failing to address either the structure or the performance assessment problems. Finally, on the basis of the delineation of problems, we outline components of a more effective reform proposal, including bringing all research under federal oversight, a permanent advisory committee to address recurrent ethical issues in clinical research, mandatory single-time review for multicenter research protocols, additional financial support for IRB functions, and a standardized system for collecting and disseminating data on both adverse events and the performance assessment of IRBs.

The limitations of "vulnerability" as a protection for human research participants.

Vulnerability is one of the least examined concepts in research ethics. Vulnerability was linked in the Belmont Report to questions of justice in the selection of subjects. Regulations and policy documents regarding the ethical conduct of research have focused on vulnerability in terms of limitations of the capacity to provide informed consent. Other interpretations of vulnerability have emphasized unequal power relationships between politically and economically disadvantaged groups and investigators or sponsors. So many groups are now considered to be vulnerable in the context of research, particularly international research, that the concept has lost force. In addition, classifying groups as vulnerable not only stereotypes them, but also may not reliably protect many individuals from harm. Certain individuals require ongoing protections of the kind already established in law and regulation, but attention must also be focused on characteristics of the research protocol and environment that present ethical challenges.

Nobel prize winner trading card (CIRCA 1952). Elie Metchnikoff.

Russian doctor and bacteriologist, born in Ivanowca in 1845. He began his studies in Kharkov, continuing them at the Universities of Giessen, Gothingen, and Munich, later being named Professor of Zoology in Odessa in 1870. In the Canary Islands, he completed some anthropological works, but dedicated himself especially to studies of marine fauna. In 1887, much taken by the work of Pasteur, he wrote to him asking for a position in his laboratories; in a short time he became one of the principal collaborators with the master, especially in works concerning bacteriology. These were an inspiration to him, and led him to his famous theory of phagocytosis, the defensive act whereby white blood cells protect an organism against pathogenic microbes. Metchnikoff supposed that old age was avoidable, and subscribed to the materialistic school of thought. He was awarded the Nobel Prize in 1908. (With the complements of the Jose Lopez Luis Cigarillo Factory, Tenerife).

Requiring consent vs. waiving consent for medical records research: a Minnesota law vs. the U.S. (HIPAA) privacy rule.

The use of medical records in research can yield information that is difficult to obtain by other means. When such records are released to investigators in identifiable form, however, substantial privacy and confidentiality risks may be created. These risks become more common and more serious as medical records move to an electronic format. In 1996, the state of Minnesota enacted legislation with respect to consent requirements for the use of medical records in research. This legislation has been widely criticized because--it is claimed--it creates an unnecessary impediment to research. In this article, we show that these arguments rest upon misinterpretation and/or misrepresentation of the 1996 legislation. A consent requirement had actually been present in Minnesota since 1976 (though codified in a patient rights statute rather than a privacy statute). The 1996 law does not require specific consent, as often claimed, but rather only a general authorization. The campaign against the Minnesota legislation appears to have been motivated by concern with respect to the then impending federal privacy rule. The HIPAA rule, as enacted, is in fact less stringent with respect to consent than the Minnesota consent law. On the other hand, the Minnesota consent law has not been effectively applied or enforced. As we change the way we manage sensitive medical information, new efforts are needed to provide protection against the confidentiality risks in research. Patient consent is an important tool in this regard. New instrumentalities are needed to solicit and document consent.

Hypotensive reaction during staphylococcal protein A column therapy in a patient with anomalous degradation of bradykinin and Des-Arg9-bradykinin after contact activation.

BACKGROUND: Hypotensive reactions have occurred in patients taking angiotensin converting enzyme (ACE) inhibitors after infusion of blood previously in contact with negatively charged surfaces capable of generating kinins, which accumulate when ACE, a kininase, is inhibited. A patient with anomalous bradykinin (BK) metabolism who experienced hypotension during extracorporeal staphylococcal protein A (SPA) therapy while on an ACE inhibitor was studied. CASE REPORT: A patient with mitomycin-associated hemolytic-uremic syndrome received SPA treatments after her ACE inhibitor, lisinopril, was held. Lisinopril was restarted before her 18th SPA treatment, and immediately after return of treated plasma she developed facial redness and hypotension, which resolved after the return stopped and recurred when restarted. To study formation and degradation of kinins, exposed her plasma to glass beads. We found a normal kinin formation rate but an abnormal degradation and accumulation of Des-Arg9-BK. The kinin degradation enzymes ACE, aminopeptidase P (APP), and carboxypeptidase N (CPN) were measured while on an ACE inhibitor, showing absence of ACE activity, low APP, but normal CPN. CONCLUSION: This patient's vasodilation and hypotension during SPA therapy was associated with a pre- existing anomaly of BK metabolism. Her ACE inhibitor shifted degradation toward Des-Arg9-BK formation, and her low APP was associated with a prolonged t50 and accumulation of the vasoactive Des-Arg9-BK.

Cholecystitis as the presenting manifestation of acute myeloid leukemia: report of a case.

We report a case of acute leukemia, which presented as cholecystitis in a previously healthy middle-aged adult. Leukemic involvement of the gastrointestinal tract is a well-known clinicopathological entity. However, leukemic infiltration of the gall bladder wall is a rare occurrence. It has only been previously described in the setting of relapsed disease and, to our knowledge, has never been reported as the primary manifestation of de novo acute leukemia. The patient in question was treated with standard induction and consolidation chemotherapy and remains in complete remission 19 months after his presentation with symptoms consistent with cholecystitis.