Trial of an undergraduate medical care education program for smoking cessation with the participation of simulated patients / 医学教育

  A 4–year trial of an undergraduate medical care education program for smoking cessation with the participation of simulated patients is described. Simulated medical care with the participation of simulated patients is thought to motivate medical students to learn clinical skills for smoking cessation. However, simulated medical care for smoking cessation is difficult to plan when both the medical students and the simulated patients are nonsmokers.

The current state of patient education for opioids by doctors, nurses and pharmacists, and evaluation of a pamphlet

The first step of cancer medical treatment is to eliminate anxiety about opioids. It is recommended to use printed matter in the "Guideline for Cancer Pain Management" edited by Japanese Society of Palliative Medicine,but few medical professionals actually use it. We developed the Opioids' pamphlet designed by Aichi Prefectural Society of Hospital Pharmacists; abbreviated OPA. This pamphlet is little burdened for readers; focusing on eliminating anxiety about opioids. Evaluation of the utility of the OPA and the actual conditions of patient education about the use of opioids by medical professionals were investigated, since there have been no reports on these issues. A questionnaire survey was conducted in hospitals with more than 150 beds in Aichi Prefecture. It targeted doctors, pharmacists and nurses who were practicing palliative care using opioids. There were many pharmacists and nurses who had been consulted about opioids, and most of the consultations were about addiction. 60% of pharmacists and 30% of nurses voluntarily performed patient education. Awareness of the guideline for of cancer pain management was low. OPA, which was reviewed based on the guideline, was applicable to 99% of the cases where the nurses were consulted. Its size and contents were highly acclaimed. Therefore, OPA is extremely valuable in clinical practice. Palliat Care Res 2009; 4(1): 214-227

Evaluation of the effect of analgesics for cancer patients using their pain descriptions

<b>Purpose</b>: The present study aims to evaluate the effect of analgesics in cancer patients based on their pain descriptions. <b>Methods</b>: The relationship between the words that patients used to describe their pain due to cancer and the efficacy of treatment with analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs) or opioids was evaluated. <b>Results</b>: We recorded 529words that were used by 164patients to describe their pain and pain quality and classified them into 108types of pain.For patients who used the actual word 'dull' or one with a similar meaning, treatment with opioids was effective. However, treatment with opioids was less effective in patients who used words such as "numb" and "tingling". <b>Conclusion</b>: We were able to gain a good understanding of cancer pain by listening to the actual words that patients used when complaining of pain. These findings suggested that we could choose a suitable medication through evaluation of the actual words cancer patients used to describe their pain and successfully relieve their pain. Palliat Care Res 2009: 4(1): 207-213

Quality of life improvement in patients diagnosed with hormone refractory prostate cancer with bone metastasis as a result of chemotherapy and the administration of zoledronic acid

Bone metastases occur in patients who have developed prostate cancer, and severely compromise the patient's quality of life. Here, we evaluated the quality of life in our inpatients diagnosed with prostate cancer with multiple bone metastases and bone pain. In our study, we evaluated pain using a pain diary, investigated the palliative effects of opioid dose, and assessed the quality of life using SF-36. The administration of chemotherapy and zoledronic acid (ZA) resulted in pain palliation, an anti tumor effect and improvements in the quality of life. We suggest that the administration of ZA might be an effective clinical strategy for multimodality advanced solid cancer therapy. We conclude that a 'combined' examination, in which a pain diary evaluating pain is considered in association with an SF-36 assessment evaluating quality of life is crucial to patient care. Palliat Care Res 2008 ; 3(2) : 308-315

Experimental gastrointestinal allergy enhances pulmonary responses to specific and unrelated allergens.

BACKGROUND: Gastrointestinal allergy often precedes or coexists with respiratory allergy. OBJECTIVE: We hypothesized that established experimental gastrointestinal allergy would prime for the development of allergic respiratory responses. METHODS: BALB/c mice were sensitized with ovalbumin (OVA) in the presence of aluminum potassium sulfate and then subjected to intragastric saline or OVA challenges. After the development of allergen-induced gastrointestinal allergy, mice were intranasally exposed to either saline, OVA, or a neoaeroallergen house dust mite (HDM) extract. Airway inflammation (eg, bronchoalveolar lavage fluid cellularity, cytokine levels, and OVA-specific antibody levels) and airway responsiveness to methacholine exposure were assessed after intranasal allergen exposure. RESULTS: A single intranasal exposure to OVA induced significantly more airway inflammation in intragastric OVA-challenged mice compared with that seen in intragastric saline-treated mice. Kinetic analysis revealed that the observed amplification of lung inflammation was sustained for up to 12 days after the last intragastric OVA challenge after resolution of blood eosinophilia. When mice with gastrointestinal allergy were repeatedly challenged with HDM in the respiratory tract, they experienced enhanced airway inflammation, including bronchoalveolar lavage fluid eosinophilia and increased IL-13 levels. CONCLUSION: Taken together, our results demonstrate that OVA-induced gastrointestinal allergy enhances not only allergic airway responses to OVA but also to HDM, an unrelated aeroallergen. CLINICAL IMPLICATIONS: Experimental gastrointestinal allergy primes for responses to allergens in the respiratory tract, enhancing antigen-specific antibody and T(H)2 cytokine production, airway inflammation, and airway hyperresponsiveness.

Epicutaneous aeroallergen exposure induces systemic TH2 immunity that predisposes to allergic nasal responses.

BACKGROUND: Atopic individuals are predisposed to mounting vigorous T(H)2-type immune responses to environmental allergens. The skin is often the first organ that manifests allergic disease and may provide an early entry point for antigen sensitization. OBJECTIVE: We sought to determine whether epicutaneous exposure to the aeroallergen Aspergillus fumigatus induces nasal allergic responses. Furthermore, we aimed to examine the mechanism involved. METHODS: Wild-type and signal transducer and activator of transcription 6 (STAT6)-deficient mice were exposed to epicutaneous A fumigatus and control antigen ovalbumin. Nasal inflammation and responsiveness to methacholine were monitored. RESULTS: Exposure to epicutaneous A fumigatus antigen induced a marked atopic dermatitis-like phenotype in a manner significantly more efficient than epicutaneous ovalbumin. A single A fumigatus intranasal challenge induced clinical nasal responses and hyperresponsiveness to methacholine in the nose as manifested by nasal symptoms, accompanied by allergic airway and nasal inflammation. Mechanistic analysis using gene-targeted mice revealed that the clinical nasal responses and hyperresponsiveness were STAT6-dependent. Although STAT6 was required for changes in nasal responses, it was not required for epicutaneous pathology except eosinophilia. CONCLUSION: Epicutaneous exposure to the aeroallergen A fumigatus potently primes for STAT6-dependent nasal responses. These results draw attention to the cooperative interaction between the nasal tract and skin. CLINICAL IMPLICATIONS: The skin is a potent site for antigen sensitization in the development of experimental allergic rhinitis.

The FIP1L1-PDGFRA fusion gene cooperates with IL-5 to induce murine hypereosinophilic syndrome (HES)/chronic eosinophilic leukemia (CEL)-like disease.

Dysregulated tyrosine kinase activity by the Fip1-like1 (FIP1L1)-platelet-derived growth factor receptor alpha (PDGFRA) (F/P) fusion gene has been identified as a cause of clonal hypereosinophilic syndrome (HES), called F/P-positive chronic eosinophilic leukemia (CEL) in humans. However, transplantation of F/P-transduced hematopoietic stem cells/progenitors (F/P(+) HSCs/Ps) into mice results in a chronic myelogenous leukemia-like disease, which does not resemble HES. Because a subgroup of patients with HES show T-cell-dependent interleukin-5 (IL-5) overexpression, we determined if expression of the F/P fusion gene in the presence of transgenic T-cell IL-5 overexpression in mice induces HES-like disease. Mice that received a transplant of CD2-IL-5-transgenic F/P(+) HSC/Ps (IL-5Tg-F/P) developed intense leukocytosis, strikingly high eosinophilia, and eosinophilic infiltration of nonhematopoietic as well as hematopoietic tissues, a phenotype resembling human HES. The disease phenotype was transferable to secondary transplant recipients of a high cell dose, suggesting involvement of a short-term repopulating stem cell or an early myeloid progenitor. Induction of significant eosinophilia was specific for F/P since expression of another fusion oncogene, p210-BCR/ABL, in the presence of IL-5 overexpression was characterized by a significantly lower eosinophilia than IL-5Tg-F/P recipients. These results suggest that F/P is not sufficient to induce a HES/CEL-like disease but requires a second event associated with IL-5 overexpression.

Epicutaneous antigen exposure primes for experimental eosinophilic esophagitis in mice.

BACKGROUND & AIMS: Eosinophilic esophagitis (EE) is frequently associated with atopic disease, including dermatitis and asthma. Data are emerging that atopic skin may provide an early entry point for antigen sensitization. We aimed to test the hypothesis that epicutaneous exposure to antigen primes for subsequent respiratory antigen-induced EE. METHODS: Wild-type and genetically engineered mice were subjected to epicutaneous antigen sensitization and the development of experimental EE, and immune responses were examined. RESULTS: We show that exposure to antigen via the epicutaneous route primes for marked eosinophilic inflammation in the esophagus triggered by a single airway antigen challenge. The development of experimental EE is associated with significant skin eosinophilia, accelerated bone marrow eosinophilopoiesis, blood eosinophilia, and large increases in serum antigen-specific immunoglobulin G1/immunoglobulin E using ovalbumin or Aspergillus fumigatus as the epicutaneous antigen. Mechanistic analysis with gene-targeted mice showed that interleukin-5 was required for esophageal eosinophilia and that interleukin-4, interleukin-13, and STAT6 contributed to a lesser extent. CONCLUSIONS: These findings provide the first evidence that epicutaneous exposure to allergens potently primes for EE via a Th2-dependent mechanism.

Identification of a cooperative mechanism involving interleukin-13 and eotaxin-2 in experimental allergic lung inflammation.

Pulmonary eosinophilia, a hallmark pathologic feature of allergic lung disease, is regulated by interleukin-13 (IL-13) as well as the eotaxin chemokines, but the specific role of these cytokines and their cooperative interaction are only partially understood. First, we elucidated the essential role of IL-13 in the induction of the eotaxins by comparing IL-13 gene-targeted mice with wild type control mice by using an ovalbumin-induced model of allergic airway inflammation. Notably, ovalbumin-induced expressions of eotaxin-1 and eotaxin-2 mRNA in the lungs were almost completely dependent upon IL-13. Second, in order to address the specific role of eotaxin-2 in IL-13-induced pulmonary eosinophilia, we generated eotaxin-2 gene-deficient mice by homologous recombination. Notably, in contrast to observations made in eotaxin-1-deficient mice, eotaxin-2-deficient mice had normal base-line eosinophil levels in the hematopoietic tissues and gastrointestinal tract. However, following intratracheal IL-13 administration, eotaxin-2-deficient mice showed a profound reduction in airway eosinophilia compared with wild type mice. Most interestingly, the level of peribronchial lung tissue eosinophils in IL-13-treated eotaxin-2-deficient mice was indistinguishable from wild type mice. Furthermore, IL-13 lung transgenic mice genetically engineered to be deficient in eotaxin-2 had a marked reduction of luminal eosinophils. Mechanistic analysis identified IL13-induced eotaxin-2 expression by macrophages in a distinct lung compartment (luminal inflammatory cells) compared with eotaxin-1, which was expressed solely in the tissue. Taken together, these results demonstrate a cooperative mechanism between IL-13 and eotaxin-2. In particular, IL-13 mediates allergen-induced eotaxin-2 expression, and eotaxin-2 mediates IL-13-induced airway eosinophilia.

The Effect of Saiko-ka-ryukotsu-borei-to(Chai-Hu-Jia-Long-Gu-Mu-Li-Tang) and Saiko-keishi kankyo-to(Chai-Hu-Gui-Zhi-Gan-Jiang-Tang) on the Monoamines and their Metabolism in Mouse Brains / 日本東洋医学雑誌

In Chinese medicine, Saiko-ka-ryukotsu-borei -to (SRT; Chai-hu-jia-long-gu-mu-li-tang) and Saiko-keishi-kankyo-to (SKT; Chai-hu-gui-zhi-gan-jiang-tang) are frequently used for patients with nervous constitutions who exhibit psychoneurotic symptoms. Specifically, SRT is used for patients of the excessive constitution type (Shi Zheng), and SKT is used for patients of the deficient constitution type (Xu Zheng).<br>In this study, in order to clarify the action of SRT and SKT on the central nervous system, the effects of these formulas on the monoamines and their metabolism in discrete brain regions in mice were examined.<br>1) Single-dose administration of SRT and SKT increased the levels of neurotransmitters and stimulated the metabolism in the dopaminergic nervous system of the corpus striatum (including the serotonergic nervous system for SRT).<br>2) Repeated administration of SRT stimulated the metabolism in the dopaminergic nervous system of the hypothalamus and hippocampus, and inhibited metabolism in the adrenergic nervous system. On the other hand, SKT stimulated dopamine metabolism in the hippocampus and inhibited the metabolism of serotonin.<br>From these results, it became apparent that single-dose administration of SRT and SKT caused the hyperfunction of the dopaminergic nervous system, and that repeated administration of the agents caused the hyperfunction of the dopaminergic nervous system and the dysfunction of the serotonergic nervous system. This suggests that the actions of SRT and SKT on the central nervous systems may exert an influence on the regulation of psychoneuroic symptoms by stimulating the doperminergic nervous system and inhibiting the serotonergic nervous system.

Effect of Saiko-ka-ryukotsu-borei-to on the Monoamine-Related Substances in Several Regions of Mouse Brain / 日本東洋医学雑誌

We studied the effect of Saiko-ka-ryukotsu-borei-to (crude extract powder for research purposes) on central monoamine-related substances in mice. The formulation was given in a dose of 50mg/kg or 400mg/kg and was administered once or repeatedly (twice a day for seven days). The brain was removed and segmented in the conventional method. The monoamine-related substances were measured by a method using HPLC-ECD. The main results were as follows. The single or repeated administration of 50mg/kg increased DOPAC and HVA contents in the cerebral cortex. In the hypothalamus, the single 50mg/kg treatment decreased NE, and the repeated 50mg/kg treatment decreased NE but increased DOPA. In the corpus striatum, the single 50mg/kg administration increased DA, DOPAC, HVA, and 5-HIAA while the repeated administration increased NE and MHPG as well. In this region, the single 400mg/kg treatment increased NE and 5-HIAA, and the repeated treatment increased NE. In the hyppocampus, the repeated 50mg/kg treatment increased MHPG, and the repeated 400mg/kg treatment decreased HVA. These results indicate that the effect of this formulation on murine brain monoamines is greater at 50mg/kg than at 400mg/kg and that the effect varies among the regions of the brain.