Over the last 40 years, problem-based learning (PBL) has swept the world of medical education. Small-group, self-directed, and self-assessed PBL is a use of the PBL tutorial which embodies most of the principles known to improve learning. The principle of self-directed learning is extremely important. Learners of today have to deal with enlarging and renewing knowledge of medical science. To create an environment in which learners would form self-directed study habits that would become the bases for life-long self-education is essential. The PBL tutorial is a good option for creating this educational environment.
There are social needs for doctors to practice evidence-based medicine. Today's information explosion also affects patient attitudes toward their healthcare issues. Communication skills are also needed to create a partnership with patients and staff. Small-group learning in the PBL tutorial can be used to develop generic skills and attitudes, such as teamwork, cooperation, and presentation skills. PBL has positive effects on knowledge application and clinical performance rather than on knowledge acquisition. The PBL tutorial is a good educational method for dealing with these demands of today. Team-based learning is also an attractive educational method, but its concepts are different from those of PBL. We could design team-based learning to develop a linkage between lectures in a large classroom and PBL.
There must be integrated institutional responsibility in a medical education program for the overall design, management, and evaluation of a coherent and coordinated curriculum. There is evidence that graduates of PBL curricula demonstrate equivalent or superior professional competencies compared with graduates of more traditional curricula. The concepts and philosophies of PBL embody the flexibility and adaptability necessary to meet the challenges of medical education.

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Patients with cancer-related anorexia (CRA) have a lack of appetite, early satiety, taste changes, poor performance status, and diminished quality of life. Megestrol acetate is a standard treatment for CRA. Recently, olanzapine has been reported to be effective for treating refractory nausea and vomiting induced by chemotherapy in patients with cancer. A clinical trial has found that the combination of megestrol acetate and olanzapine is effective for patients with CRA. In this article we describe the treatment of CRA using olanzapine.

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We examined whether 0.1% 2,4-Dinitorofluorobenzene (DNFB), which is a concentration insufficient to induce contact dermatitis with a single application, can induce dermatitis with repeated applications. 0.1% DNFB was painted on the shaved backs of C57BL/6 mice 2 consecutive days a week and 6 applications (3 weeks) induced allergic contact dermatitis. A hapten-specific lymphocyte proliferative response was observed in regional lymph node cells obtained 2 applictions (1 week) of 0.1% DNFB. Four applications (2 weeks) of 0.1% DNFB did not elicit dermatitis, despite the appearance of hapten-specific lymphocytes; therefore, immunological memory is not sufficient to complete the sensitization phase. Interferon (IFN)-γ was produced at 1 week and in significantly higher amounts at 2 weeks. The redox status of regional lymph node cells was examined, because reductive cells have been reported to produce IFN-γ. The number of reductive cells was also increased at 1 week and significantly higher at 2 weeks. Most of the increased reductive cells were considered to be antigen non-specific because even repeated immunization can not induce such a high number of antigen specific cells. If the higher number of antigen non-specific reductive cells play a crucial role in completing the sensitization phase, even irrelevant antigens could induce dermatitis after 4 applications (2 weeks) of DNFB. Although 2.5% or 3.5% oxazolone could not induce dermatitis with a single application, it could induce dermatitis, if applied following 4 applications (2 weeks) of 0.1% DNFB. These results demonstrate that the sensitization phase of allergic contact dermatitis consists of at least 2 steps: the first step, which is antigen specific, is the appearance of antigen specific lymphocytes in regional lymph nodes, and the second step, which is antigen non-specific, is increases in IFN-γ production and the number of reductive cells. Entry of an antigen to the skin plays a crucial role in the response to all antigens.

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We reviewed the literature to evaluate the current status of hiatal mesh repair in Western countries and introduce our procedure using Parietex^TM composite mesh. Faced with large hiatal defects and a high recurrence rate, some early surgeons advocated the use of artificial material for closure of the defect. The first report of the use of a prosthetic material to reinforce crural repair was in 1960. Thereafter, some surgeons reported that mesh prosthesis-reinforced hiatus hernia repair was effective and appeared to have a low recurrence rate. Mesh hernia repair is the standard procedure to treat giant hiatal hernia in Western countries. However, this procedure is less common in Japan, and indications for mesh use have not been established. We determined the indication at our institution as follows: 1) type III hiatal hernia, 2) hiatal defect size > 5cm, and 3) weak crus that tears easily with crural repair. During the operation, we insert and use 5 trocars and return the stomach to its normal position. The hernia sac should be removed as far as possible to prevent hernia recurrence. We suture the crus and place mesh to reinforce the hiatal defect. The mesh was anchored with tacks, which allow the mesh to be easily placed. Parietex^TM composite mesh, the first mesh for hiatal hernia repair introduced in Japan, is coated on 1 side with a protective collagen-based barrier to help prevent tissue attachment. The mesh is created in the shape of the hiatus to buttress the primary repair by reinforcing the approximation of the crus on either side of the esophagus. We are satisfied with this mesh because it makes hiatal repair a safe and simple procedure. In conclusion, mesh replacement in hiatal hernia repair should be promoted, and the operative indications for hiatal mesh repair should be determined in Japan.

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Most of the candidate tissues for in vivo gene transfer are made of quiescent cells, such as from the brain, liver, and muscle. Thus, the optimal vector should infect non-dividing cells. Recently, many type of adeno-associated virus (AAV) vectors have been developed and used in vivo gene transfer. This technical note focuses on the in vivo gene transfer using AAV vectors. We discuss about how to choose the appropriate viral vector to transduce target organs in vivo.

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We review our recent collaborative study, performed by computational physicists and biochemists, of the enzyme effects due to the drug called febuxostat. Febuxostat, which was recently approved in the US, European Union and Japan for treatment of gout, inhibits xanthine oxidoreductase (XOR)-mediated generation of uric acid during purine catabolism. Experiments have shown that febuxostat has strong effects on mammalian XOR but not on bacterial XOR, although the two enzymes have similar three-dimensional structures. To clarify the difference in the inhibitory power of febuxostat, we performed docking and molecular dynamics simulations for mammalian and bacterial XORs. We found that the static structures are not sufficient to explain the binding difference and that important interactions occur between febuxostat and the active region of the enzymes which suggests a better strategy for drug design.

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