PET and functional anatomic fusion imaging in lung and breast cancers

Metabolic imaging with PET is an established adjunct to anatomic imaging methods in patients with bronchial and breast cancers. The functional anatomic fusion imaging with PET/CT can further improve staging and restaging of patients. PET/CT can influence the planning of a surgical intervention or radiation treatment at staging and in patients with suspected locoregional recurrence. The use of a PET/CT whole body imaging protocol may identify extended disease earlier than conventional imaging methods and thus influence treatment decisions.     

An online discussion for medical faculty: an experiment that failed.

OBJECTIVE: Although online discussion groups are being used with increasing frequency in undergraduate and postgraduate education, their usefulness in faculty development has not been explored. The goal of this innovation was to offer an online discussion group following a faculty development workshop in order to reinforce workshop concepts and to allow participants to seek advice related to specific teaching and learning problems. We also wanted to assess the benefits of this educational tool. DESCRIPTION: We originally wanted to implement an online discussion group following a one-day workshop "The "Problem" Resident: Whose Problem Is It?" However, once this proposal was presented to our academic administrators, they asked us not to implement the discussion group because of concerns related to confidentiality and due process. They were worried that an online discussion might replace the faculty's evaluation and promotion guidelines, that teachers might no longer go to the "right" person to discuss a problem, and that we would give teachers a false sense of security. To respect these concerns, we changed the discussion topic and decided to implement an online discussion following a workshop "Promoting Interaction in Small-group Teaching." We chose this venue because it was less "emotionally charged" and because online discussions are seen as a potential adjunct to small-group teaching. We introduced the idea of a facilitated WebCT group discussion at the end of the workshop, and gave faculty members clear instructions on how to access the discussion group. Most of the workshop participants liked the idea of a follow-up to the workshop, but they preferred an e-mail listserv. We therefore decided to offer the WebCT discussion group to half of the participants, and an e-mail listserv to the others. To initiate the discussion, we posted several issues for both groups, and we awaited the participants' responses. To our surprise, only two individuals (8%) responded on the e-mail listserv, after several attempts to stimulate discussion. DISCUSSION: In looking back at our "medical experiment" we were disappointed that our efforts to facilitate an online discussion following a faculty development workshop were not successful. However, based on personal reflections and conversations with a number of the workshop participants, we feel that some important lessons were learned. Time and competing demands clearly pose a major barrier. In addition, the "perceived need" of the initiative is critical. Our faculty members did not see the need for discussing interactive small-group teaching techniques online. Faculty members' comfort with technology must also be considered. Many of our teachers were not familiar with the potential uses of online learning. Moving faculty development beyond workshops also remains a challenge. With these lessons in mind, we plan to initiate another online discussion with faculty members, based on a need that they have defined around a topic that they have identified as critical to their own development as faculty members. We continue to believe that follow-up activities are essential in faculty development and that we need to further assess the potential value of this educational method.     

Influence of the alternative sigma(28) factor on virulence and flagellum expression of Legionella pneumophila

The fliA gene of Legionella pneumophila encoding the alternative sigma(28) factor was inactivated by introducing a kanamycin resistance cassette. Electron microscopy and Western blot analysis revealed that the fliA mutant strain is aflagellate and expresses no flagellin. Reporter gene assays indicated that the flaA promoter is not active in the fliA mutant strain. The fliA mutant strain multiplied less effectively in coculture with amoebae than the wild-type strain and was not able to replicate in coculture with Dictyostelium discoideum.     

Flagellum of Legionella pneumophila positively affects the early phase of infection of eukaryotic host cells

Legionella pneumophila, the etiologic agent of Legionnaires' disease, contains a single, monopolar flagellum which is composed of one major subunit, the FlaA protein. To evaluate the role of the flagellum in the pathogenesis and ecology of Legionella, the flaA gene of L. pneumophila Corby was mutagenized by introduction of a kanamycin resistance cassette. Immunoblots with antiflagellin-specific polyclonal antiserum, electron microscopy, and motility assays confirmed that the specific flagellar mutant L. pneumophila Corby KH3 was nonflagellated. The redelivery of the intact flaA gene into the chromosome (L. pneumophila Corby CD10) completely restored flagellation and motility. Coculture studies showed that the invasion efficiency of the flaA mutant was moderately reduced in amoebae and severely reduced in HL-60 cells. In contrast, adhesion and the intracellular rate of replication remained unaffected. Taking these results together, we have demonstrated that the flagellum of L. pneumophila positively affects the establishment of infection by facilitating the encounter of the host cell as well as by enhancing the invasion capacity.     

Decisions about sectioning and medicating of schizophrenic patients in Germany and England--results of a comparative study

Questionnaires with three case summaries have been presented to 143 psychiatrists in Germany and 27 in England. All three case summaries regard patients with schizophrenia who either show risk to themselves or others. The psychiatrists were asked whether they would recommend sectioning and furthermore whether they would recommend treatment against the patient's will. In the case regarding a risk to others there was widespread approval of sectioning and treatment (Germany 85 %, England 93 %) against the patient's will. Significant differences were seen in the cases of risk to the patients themselves with regards to treatment against the patient's will. This was the case with a scenario involving a young man with his first presentation of schizophrenia as well as in the case of a middle aged man presenting with chronic psychotic symptoms and self-neglect (approval in England: 96 % and 93 % respectively, in Germany: 63 % and 59 % respectively, p < 0.001 for both). When a logistic regression was performed the country of work was the most important predictive factor in deciding whether or not to treat a patient against his will.     

Erhöhter postoperativer Schmerz nach orthopädischen Operationen

The aim of this study was to examine whether depression is a strong predictor of elevated postoperative pain levels following orthopedic surgery and whether the implementation of standardized pain management is more beneficial for patients with depression. We performed a non-randomized, prospective study with two different groups of patients who underwent orthopedic surgery. Group 1 (n=249) received non-standardized pain therapy whereas group 2 (n = 243) was treated with a standardized pain management concept. Effects of the treatment were monitored with a VAS-based pain assessment protocol. Depression was measured preoperatively with the self-reported Patient Health Questionnaire (PHQ-9). Patients with the probable diagnosis of a current episode of major depression showed significantly higher postoperative pain than patients without a depressive episode. On the other hand, patients with depression benefited from the implementation of standardized pain management. Our data suggest a predictive value of depression for severe postoperative pain. Patients with depression benefited from standardized postoperative pain therapy, but were still suffering from significantly higher postoperative pain.     

A novel function for transglutaminase 1: Attachment of long-chain ω-hydroxyceramides to involucrin by ester bond formation

Transglutaminases (TGases) are defined as enzymes capable of forming isopeptide bonds by transfer of an amine onto glutaminyl residues of a protein. Here we show that the membrane-bound form of the TGase 1 enzyme can also form ester bonds between specific glutaminyl residues of human involucrin and a synthetic analog of epidermal specific omega-hydroxyceramides. The formation of a approximately 5-nm-thick lipid envelope on the surface of epidermal keratinocytes is an important component of normal barrier function. The lipid envelope consists of omega-hydroxyceramides covalently linked by ester bonds to cornified envelope proteins, most abundantly to involucrin. We synthesized an analog of natural omega-hydroxyceramides N-[16-(16-hydroxyhexadecyl)oxypalmitoyl]sphingosine (lipid Z). When recombinant human TGase 1 and involucrin were reacted on the surface of synthetic lipid vesicles containing lipid Z, lipid Z was attached to involucrin and formed saponifiable protein-lipid adducts. By mass spectroscopy and sequencing of tryptic lipopeptides, the ester linkage formation used involucrin glutamine residues 107, 118, 122, 133, and 496 by converting the gamma-carboxamido groups to lipid esters. Several of these residues have been found previously to be attached to ceramides in vivo. Mass spectrometric analysis after acetonide derivatization also revealed that ester formation involved primarily the omega-hydroxyl group of lipid Z. Our data reveal a dual role for TGase 1 in epidermal barrier formation and provide insights into the pathophysiology of lamellar ichthyosis resulting from defects of TGase 1 enzyme.