Dopamine inhibition and the adaptation of behavior to ongoing reality

Spontaneous confabulation is a rare memory disorder resulting from orbitofrontal damage or disconnection. Patients act on the basis of memories that do not pertain to the current situation, and are disoriented. No medical treatment is known. Recent studies suggest that subcortical dopaminergic structures are involved in the selection of currently relevant memories. We present a patient who regained the ability to adapt thought and behavior to ongoing reality when treated with risperidone, a dopamine antagonist.

Patient satisfaction with primary care: an observational study comparing anthroposophic and conventional care

BACKGROUND: This study is part of a cross-sectional evaluation of complementary medicine providers in primary care in Switzerland. It compares patient satisfaction with anthroposophic medicine (AM) and conventional medicine (CON). METHODS: We collected baseline data on structural characteristics of the physicians and their practices and health status and demographics of the patients. Four weeks later patients assessed their satisfaction with the received treatment (five items, four point rating scale) and evaluated the praxis care (validated 23-item questionnaire, five point rating scale). 1946 adult patients of 71 CON and 32 AM primary care physicians participated. RESULTS: 1. Baseline characteristics: AM patients were more likely female (75.6% vs. 59.0%, p < 0.001) and had higher education (38.6% vs. 24.7%, p < 0.001). They suffered more often from chronic illnesses (52.8% vs. 46.2%, p = 0.015) and cancer (7.4% vs. 1.1%). AM consultations lasted on average 23,3 minutes (CON: 16,8 minutes, p < 0.001). 2. Satisfaction: More AM patients expressed a general treatment satisfaction (56.1% vs. 43.4%, p < 0.001) and saw their expectations completely fulfilled at follow-up (38.7% vs. 32.6%, p < 0.001). AM patients reported significantly fewer adverse side effects (9.3% vs. 15.4%, p = 0.003), and more other positive effects from treatment (31.7% vs. 17.1%, p < 0.001). Europep: AM patients appreciated that their physicians listened to them (80.0% vs. 67.1%, p < 0.001), spent more time (76.5% vs. 61.7%, p < 0.001), had more interest in their personal situation (74.6% vs. 60.3%, p < 0.001), involved them more in decisions about their medical care (67.8% vs. 58.4%, p = 0.022), and made it easy to tell the physician about their problems (71.6% vs. 62.9%, p = 0.023). AM patients gave significantly better rating as to information and support (in 3 of 4 items p [less than or equal to] 0.044) and for thoroughness (70.4% vs. 56.5%, p < 0.001). CONCLUSION: AM patients were significantly more satisfied and rated their physicians as valuable partners in the treatment. This suggests that subject to certain limitations, AM therapy may be beneficial in primary care. To confirm this, more detailed qualitative studies would be necessary.

Arthroscopically assisted removal of intraosseous ganglion cysts of the distal tibia

Intraosseous ganglia of the distal tibia are rare. We evaluated the feasibility of surgically treating these lesions with an arthroscopically assisted technique. Five patients with symptomatic distal tibial ganglia underwent surgical curettage and excision with this technique. All patients underwent débridement of the chondral lesion and hypertrophied synovial lining when present, probing of the portal to the ganglion, and subsequently thorough curettage with bone grafting performed through a cortical window made from a separate small incision. Biopsy confirmed the diagnosis in all patients. All patients had eventual relief of symptoms with good integration of bone graft at final followup. There were no recurrences at a minimum followup of 19 months (mean, 38.6 months; range, 19-69 months). Mean time for return to full function was 15.4 weeks (range, 8-17 weeks). There were no intraoperative or postoperative complications. The mean American Orthopaedic Foot and Ankle Society scores increased from 73 points (range, 67-77 points) preoperatively to 94 points (range, 90-100 points) postoperatively. Arthroscopically assisted surgical treatment of ganglia of the distal tibia in the appropriate patient is a reasonably simple technique that relieves symptoms and helps the patient to regain normal gait and full function with no recurrence (in our small series). LEVEL OF EVIDENCE: Level IV, case series. See Guidelines for Authors for a complete description of levels of evidence.

AKT/mTOR pathway activation and BCL-2 family proteins modulate the sensitivity of human small cell lung cancer cells to RAD001

PURPOSE: The Akt/mammalian target of rapamycin (mTOR) pathway is frequently activated in human cancers and plays an important role in small cell lung cancer (SCLC) biology. We investigated the potential of targeting mTOR signaling as a novel antitumor approach in SCLC. EXPERIMENTAL DESIGN: The expression of mTOR in patient specimens and in a panel of SCLC cell lines was analyzed. The effects on SCLC cell survival and downstream signaling were determined following mTOR inhibition by the rapamycin derivative RAD001 (Everolimus) or down-regulation by small interfering RNA. RESULTS: We found elevated expression of mTOR in patient specimens and SCLC cell lines, compared with normal lung tissue and normal lung epithelial cells. RAD001 treatment impaired basal and growth factor-stimulated cell growth in a panel of SCLC cell lines. Cells with increased Akt pathway activation were more sensitive to RAD001. Accordingly, a constitutive activation of the Akt/mTOR pathway was sufficient to sensitize resistant SCLC cells to the cytotoxic effect of RAD001. In the sensitive cells, RAD001 showed a strong additive effect to the proapoptotic action of the chemotherapeutic agent etoposide. Intriguingly, we observed low Bcl-2 family proteins levels in the SCLC cells with a constitutive Akt pathway activation, whereas an increased expression was detected in the RAD001-resistant SCLC cells. An antisense construct targeting Bcl-2 or a Bcl-2-specific inhibitor was able to sensitize resistant SCLC cells to RAD001. Moreover, SCLC tumor growth in vivo was significantly inhibited by RAD001. CONCLUSION: Together, our data show that inhibiting mTOR signaling with RAD001 potently disrupts growth and survival signaling in human SCLC cells.

Marginal fit of cemented and screw-retained crowns incorporated on the Straumann (ITI) Dental Implant System: an in vitro study

AIM: The aim of this study was to assess the marginal fit of crowns on the Straumann (ITI) Dental Implant System with special consideration of different casting dental materials. MATERIAL AND METHODS: Sixty porcelain-fused-to-metal crowns were fabricated: 18 crowns on standard cone abutments with an impression cylinder, partially prefabricated analogs, no coping and screw-retained (A); 18 crowns on solid abutments without an impression device, no analogs, no coping and cemented (B); and 18 crowns on solid abutments using an impression transfer cap, an analog with a shoulder, no coping and cemented (C). In each group, six crowns were made on epoxy mastercasts (Bluestar), six on synthetic plaster (Moldasynt) and six on super hard stone (Fujirock). Six additional crowns were fabricated with the transversal screw retention system onto the Octa system with impression transfer caps, metal analogs, gold copings and screw-retained (D). Impregum was used as impression material. Crowns of B and C were cemented with KetacCem. Crowns of A and D were fixed with an occlusal screw torqued at 15 N cm. Crowns were embedded, cut and polished. Under a light microscope using a magnification of x 100, the distance between the crown margin (CM) and the shoulder (marginal gap, MG) and the distance between the CM and the end of the shoulder (crown length, CL) was measured. RESULTS: MGs were 15.4+/-13.2 microm (A), 21.2+/-23.1 microm (B), 11+/-12.1 microm (C) and 10.4+/-9.3 microm (D). No statistically significantly differences using either of the casting materials were observed. CLs were -21.3+/-24.8 microm (A), 3+/-28.9 microm (B), 0.5+/-22 microm (C) and 0.1+/-15.8 microm (D). Crowns were shorter on synthetic casting materials compared with stone casts (P<0.005). CONCLUSIONS: CMs fit precisely with both cemented and screw-retained versions as well as when using no, partial or full analogs.

Mechanical signals regulating extracellular matrix gene expression in fibroblasts

Mechanical forces are essential for connective tissue homeostasis. The extracellular matrix (ECM) plays a key role in the transmission of forces generated by the organism (e.g. muscle contraction) and externally applied (e.g. gravity). The expression of specific ECM proteins such as collagens and tenascin-C, as well as of matrix metalloproteinases, involved in their turnover, is influenced by mechanical stimuli. The precise mechanisms by which mechanical strains are translated into chemical signals and lead to differential gene expression are however not fully understood. Cell-matrix adhesion sites are good candidates for hosting a "mechanosensory switch", as they transmit forces from the ECM to the cytoskeleton and vice versa by physically linking the cytoskeleton to the ECM. Integrins, transmembrane proteins located to these adhesion sites, have been shown to trigger a set of internal signaling cascades after mechanical stimulation. We have shown that the expression level of tenascin-C directly correlates with externally applied mechanical stress, as well as with RhoA/RhoA-dependent kinase-mediated cytoskeletal tension. Presumably other genes are regulated in a similar manner. The changes in ECM composition and mechanical properties derived from mechanical stress are relevant in medical intervention after ligament and tendon injury.

Surgery-related risk factors

PURPOSE OF REVIEW: The surgical procedure remains the key element in the multidisciplinary treatment of a wide variety of degenerative, traumatic, tumorous, congenital, and vascular diseases, resulting in an estimated 234 million surgical interventions worldwide each year. Undesired effects are inherent in any medical intervention, but are of particular interest in an invasive procedure for both the patient and the responsible physician. Major topics in current complication research include perception of key factors responsible for complication development, prediction, and whenever possible, prevention of complications. RECENT FINDINGS: For many years, the technical aspects of surgery and the skills of the surgeon her/himself were evaluated and considered as the main sources of surgical complications. However, recent studies identified many nontechnical perspectives, which could improve the overall quality of surgical interventions. SUMMARY: This article reviews selected, recently published data in this field and aims to point out the complexity and multidimensional facets of surgery-related risk factors.

MetaCampus REAL – ein europäischer Marktplatz für E-Learning Leistungen

This article addresses the discussion about open source solutions in the e-learning business. In contrast to critics by commercial suppliers this article comes to different conclusions. On the one hand such a discussion seems to be useless in this early state of the e-learning market. On the other hand solutions without costs might have a strong influence of which commercial suppliers could profit as well.

MetaCampus REAL – a European Marketplace for Lifelong Learning

This article addresses the discussion about open source solutions in the e-learning business. In contrast to critics by commercial suppliers this article comes to different conclusions. On the one hand such a discussion seems to be useless in this early state of the e-learning market. On the other hand solutions without costs might have a strong influence of which commercial suppliers could profit as well.