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Cancer cachexia causes anorexia and metabolic disorders, eventually leading to sarcopenia, which in turn contributes to the development of functional disabilities. Although anamorelin hydrochloride tablets are marketed to treat cancer cachexia, their efficacy varies significantly among patients. Here, we investigated the efficacy of anamorelin and the factors associated with weight gain. The factors that contributed to weight gain in patients before starting anamorelin were as follows: the patients' disease stage had not progressed to refractory cachexia based on the cancer cachexia classification of the European Palliative Care Research Collaborative; the patients had received fewer lines of anticancer treatment at the start of oral administration of anamorelin; and the patients had not met all the criteria for starting treatment with anamorelin, namely, C-reactive protein level >0.5 mg/dL, hemoglobin level <12 g/dL, and albumin level <3.2 g/dL. These results suggest that early administration of anamorelin hydrochloride tablets may increase the response rate when cancer cachexia is diagnosed.

A 32-year-old woman was diagnosed with autoimmune hemolytic anemia (AIHA) at 12 weeks of a pregnancy examination and followed up closely without treatment. At 40 weeks of gestation, she underwent emergency caesarean section because of premature rupture. On postoperative day one, the patient exhibited worsening hemolysis and tachycardia and developed high-output heart failure; she was diagnosed with Basedow disease based on the tachycardia pattern and thyroid storm based on the presence of hyperthyroidism, fever, tachycardia, and heart failure. She was administered thiamazole and potassium iodide, which improved her thyroid function, hemolytic anemia, and heart failure. AIHA is rarely associated with Basedow disease, and hemolytic anemia can be aggravated by hyperthyroidism. In pregnant women with AIHA, management of hyperthyroidism is crucial as delivery can lead to thyroid storm.

The present paper is a review of the history of the medical service system. Medical treatments were performed mainly as free services until the Edo era. In the Meiji period, the necessity of medical insurance was advocated from the point of view of health care, especially for young males. Around the end of the Taisho period, the health insurance act was established despite incomplete legislation. In 1961, the medical insurance service system was chosen as the health care system for the entire Japanese population and was completed after several revisions. Reimbursements for medical services for urological diseases are shown chronologically from the Edo era until present time and they provide interesting results. Finally, the activities of the JUA health insurance committee are summarized and are demonstrated to have a considerable impact on the present medical insurance system.

Objective: We analyzed sonographic appearance of dermatofibroma, schwannoma, small-sized venous mal- formation, glomus tumor, nodular fasciitis, and thrombus for effective use in the diagnosis., Methods: We evaluated with sonography 44 subcutaneous nodules in histopathologically proven cases., Results and Discussion: 1) Sonography was the most useful for diagnosing schwannoma. Six of 8 lesions were diagnosed correctly from sonographic appearance. They had increased posterior echo and Doppler flow signals. 2) Sonography was helpful in diagnosis of subungual glomus tumor, though malignant melano- ma should be excluded. One of 6 glomus tumors was not detected but all of the other had well-defined mar- gins and showed internal vascularity. Three subungual glomus tumors were diagnosed from sonographic appearance although 2 nonsubungual tumors were not. 3) It was difficult to diagnose nodular fasciitis with sonography. Two of 5 cases were not detected. The other 3 lesions were ill-defined, and 2 were hy- perechoic and 2 showed internal vascularity. Interval between emergence of the lesion and sonography ex- amination was important. This duration was more than 50 days in lesions not detected with sonography, about 20 days in 2 hyperechoic lesions, and 6 days in a hypoechoic lesion. 4) Dermatofibromas (n =14) were also difficult to be diagnosed. The region was very characteristic, that is, in the upper dermis. Other find- ings, such as hypoechoic appearance and well-defined margin, were nonspecific., Conclusion: Sonography was more useful for diagnosing schwannoma and glomus tumor. We have to know their characteristic appearance on sonography to use sonography effectively. [Original].

An 80-year-old man, presenting with gait disturbance and memory loss, had findings of normal pressure hydrocephalus. Primary leptomeningeal lymphoma (PLML) was diagnosed based on cytology and flow cytometry of cerebrospinal fluid obtained by examination. Gadolinium-enhanced MRI showed enhancement of the brain and spinal cord but FDG-PET/CT revealed no lymph node swelling. With intrathecal chemotherapy, meningeal lesions disappeared and the gait disturbance and memory loss improved. However, the disease recurred three months later, manifesting as left facial nerve palsy, but the symptoms disappeared in response to intrathecal chemotherapy and systemic rituximab administration. Although a tumor lesion in the spinal canal was suggested by MRI examination, the patient has maintained a good clinical course for four years with intrathecal chemotherapy every three months. PLML is a very rare disease and its diagnosis is difficult. Repeated intrathecal chemotherapy appeared to be effective against PLML in this case.

Testicular lymphoma is a rare disease, accounting for 1-2% of non-Hodgkin lymphoma and 5-9% of all testicular tumors, and has a high relapse rate with a poor prognosis. We report a patient with testicular diffuse large B-cell lymphoma (DLBCL) who relapsed after being in remission for 16 years. He had undergone orchiectomy of the right testis and was diagnosed as having DLBCL (stage IAE) at 49 years of age. After 3 cycles of CHOP, he achieved a complete remission. Orchiectomy was performed because of a left testicular tumor, and he was again diagnosed with DLBCL at the age of 65. VH3-21 was detected in lymphoma cells at the times of both the first diagnosis and the relapse based on analysis of the variable region of the immunoglobulin heavy chain. Accordingly, the lymphoma cells at relapse were confirmed to be the same clone as that which had been documented at the first diagnosis.

Immunomodulatory drugs (IMiDs) including lenalidomide, a single compound shows various pharmacological action such as the stimulation of T cells and natural killer (NK) cells, the suppression hematopoietic tumor proliferation, suppression of neo-vascularisation, and anti-inflammatory action. It has been thought that IMiDs stimulates CD8+ cytotoxic T cells primarily, it is recently shown that they also stimulate CD4+ helper-T cells similarly. Lenalidomide stimulates T cells and NK-cell through production of Th1 type cytokines IL-2 and IFN-γ from CD4+ helper-T cells. Lenalidomide also activate T cells indirectly by inhibiting regulatory T cells and myeloid derived suppressor cells (MDSC) which inhibit the activation of T cells, but controversy still exist about effects on regulatory T cells.

Herein, we report a patient with polycythemia vera (PV) who exhibited Philadelphia chromosome (Ph) positive CML-like clinical features after 13 years of hydroxycarbamide administration and successful treatment with a tyrosine kinase inhibitor (TKI). She was 64 years old when initially diagnosed with PV and was confirmed to be negative for BCR-ABL translocation. Thirteen years later, with increasing white blood cell and platelet counts, a BCR-ABL positive clone emerged and the JAK2V617F mutation disappeared. After TKI treatment, the BCR-ABL copy number decreased and the JAK2V617F mutation was again detected. Furthermore, MPN clinical features were observed. This case provides insights into the clonal divergence and growth advantage of the Ph positive clone over the MPN clone. Whether JAK2V617F is an MPN initiating event or a secondary mutation has been a point of discussion for the past several years. This issue is also considered in the present report.

Objective: Color Doppler sonography is used to distinguish malignant from benign subcutaneous nodules because many malignant tumors show an increased number of vessels. But benign lesions, such as inflammatory epidermal cysts, pilomatricomas, palmoplantar fibromatoses show vascular flow signals. We analyze diagnostic factors for subcutaneous nodules on the basis of ultrasonographic appearance including color Doppler sonography., Methods: We evaluated with sonography 79 subcutaneous nodules in histopathologically proven cases., Results and Discussion: The diagnostic findings for 28 epidermal cysts were increased posterior echo(sensitivity 77%, specificity 90%). Vascular flow signals were seen in 7 cases(25%). The signals were seen from periphery to adjacent zone of the mass. They were accompanied by inflammatory granulation tissues histologically. The percentage of blood flow may be related to the percentage of "ruptured" epidermal cysts. Pilomatricomas (n = 9) had internal echogenic foci or Doppler flow signals, and no posterior enhancement (sensitivity 89%, specificity 78%). Seven pilomatricomas showed Doppler flow signals in the mass. The percentage of flow signals is explained by the degree of internal echogenic foci because remarkable calcium deposits producing posterior acoustic shadowing prevent us from flow signals. Palmoplantar fibromatoses (n = 5) were ill-defined margins and showed internal vascularity with no posterior enhancement (sensitivity 80%, specificity 94%)., Conclusion: More benign lesions showed vascular flow signals than reported previously. We have to diagnose subcutaneous nodules referring to not only color Doppler but also gray scale sonography.

A 58-year-old woman with primary intraocular lymphoma (PIOL) of her right eye was treated with combination chemotherapy (methotrexate, procarbazine and vincristine) followed by irradiation to her brain and right eye. However, the disease recurred in the right eye four months later. She was treated with intravitreal injection of methotrexate and high-dose chemotherapy in combination with autologous stem cell transplantation after salvage therapy consisting of cytarabine, etoposide and rituximab. With this treatment strategy, she has been in remission for more than one year with no deterioration of either leukoencephalopathy or cognitive function. Intravitreal injection of methotrexate and high-dose chemotherapy may now be regarded as one of the treatment choices for relapsed PIOL.

Innate immunity is induced after sensing microbial components by pattern-recognition receptors and functions as a first line of host defense against microbes. However, innate immunity is also induced after sensing host-derived stimulatory substances such as monosodium urate crystals and causes the development of inflammatory diseases, such as gout. Therefore, a better understanding of innate immunity is required for the development of effective therapeutic treatments for infectious and inflammatory diseases. This paper summarizes recent findings on regulation of the innate immune response. Accumulating evidence has shown that the intracellular degradation system is critically involved in various cellular processes. We focused on the intracellular degradation system and have revealed the molecular mechanisms underlying regulation of the innate immune response. Ubiquitin-proteasome, autophagy and phagocyte-specific proteases most certainly regulate the innate immune response induced by infection of microbes and exposure to host-derived stimulatory substances. Therefore, intracellular degradation systems would be attractive therapeutic targets for the treatment of immune-related diseases.

A 45-year-old woman with acute myelogenous leukemia developed platelet transfusion refractoriness (PTR) after the engraftment of an allogeneic peripheral blood stem cell transplantation (PBSCT) from her multiparous sister, which was attributed to HLA antibodies that could not be detected in the patient's serum before transplantation. She achieved neutrophil engraftment by day 18 and megakaryocytopoiesis and complete donor chimerism was confirmed in the bone marrow on day 21. IgG-class HLA antibodies were detected in her serum on day 24 after PBSCT; however, on day 15, no HLA antibodies were detected. The specificity of the antibodies that emerged in the patient closely resembled that of the antibodies found in the donor. The donor had probably been immunized during pregnancy by their partner's HLA-antigens expressed by the fetus. Consequently, transplanted donor-derived cells provoked HLA antibodies in the recipient early after PBSCT, and those HLA antibodies induced PTR. The presence of HLA antibodies should be examined at least in pregnant female donors whose recipients developed PTR attributable to HLA antibodies after SCT.

The recurrent laryngeal nerve is a branch of the vagus nerve. On the right side, it branches anteriorly to the subclavian artery in the neck. In cases of malignant diseases, lymph node metastasis can lead to recurrent laryngeal nerve palsy. Patients with this condition often suffer from aspiration pneumonia, which requires tube feeding. In this case of an advanced lung cancer, we treated the involved lymph node in the neck with palliative radiotherapy, which restored normal nerve function.

The innate immune system detects pathogen-derived nucleic acids (DNA and RNA) and induces type I interferon (IFN) and other cytokines, resulting in the host defense against pathogen. We identified interferon-inducible tripartite-motif (TRIM) 56 as a regulator of double-stranded DNA-mediated type I interferon induction. TRIM56 interacted with STING and targeted it for lysine 63-linked ubiquitination. This modification induced STING dimerization, which was a prerequisite for recruitment of the antiviral kinase TBK1 and subsequent induction of IFN-beta. Taken together, these results show that TRIM56 is an interferon-inducible E3 ubiquitin ligase that modulates STING to confer double-stranded DNA-mediated innate immune responses. It is well known that Toll-like receptor 7 (TLR7) and TLR9 sense viral nucleic acids and induce production of type I interferon (IFN) by plasmacytoid dendritic cells (pDCs) to protect the host from virus infection. We showed that the IFN-inducible antiviral protein Viperin promoted TLR7- and TLR9-mediated production of type I IFN by pDCs. Viperin expression was potently induced after TLR7 or TLR9 stimulation and Viperin localized to the cytoplasmic lipid-enriched compartments, lipid bodies, in pDCs. Viperin interacted with the signal mediators IRAK1 and TRAF6 to recruit them to the lipid bodies and facilitated K63-linked ubiquitination of IRAK1 to induce the nuclear translocation of transcription factor IRF7. Thus, besides direct inhibition of viral replication, this finding reveals that Viperin mediates its antiviral function via the regulation of the TLR7 and TLR9-IRAK1 signaling axis in pDCs.

We retrospectively investigated pathological types, clinical backgrounds, treatments and prognoses in 726 adult patients with newly diagnosed malignant lymphoma in Gunma Prefecture. They consisted of 679 patients with non-Hodgkin lymphoma (B-cell type, 603; T- and NK-cell type, 76) of which 376 patients had diffuse large B-cell lymphoma (DLBCL) and 47 patients with Hodgkin lymphoma. When comparing the prognosis of DLBCL between patients receiving rituximab (R-CHOP group; n=212) and not using rituximab (CHOP group; n=126), both 3-year overall survival (73.5% vs 61.7%, p=0.010) and 3-year progression-free survival (65.1% vs 45.8%, p<0.001) were statistically better in the R-CHOP group compared to the CHOP group. Our results suggest that more than half of patients were DLBCL and the rituximab-containing regimen results in an improved prognosis for DLBCL patients.

A 55-year-old man was diagnosed with infective endocarditis( IE) of the mitral valve caused by Streptococcus sanguinis. His IE was controlled immediately after the initiation of intravenous antibiotic therapy lasting for 4 weeks. A few days before surgery, he complained of abdominal discomfort and computed tomography (CT) scan revealed rupture of the mycotic iliocolic artery aneurysm. Emergency transcatheter arterial embolization( TAE) was successfully conducted. After additional 4 weeks' intravenous antibiotic therapy, the mitral valve was replaced. Mycotic visceral artery aneurysms are rare in IE. Early diagnostic approaches and interventions such as TAE are crucial.

We report a case of fungemia caused by Scedosporium prolificans, an emerging pathogen. An 83-year-old man with myelodysplastic syndrome (MDS) and agranulocytosis was admitted for pneumonia in January 2009. He was treated with meropenem, minocycline, and gamma-globulin for pneumonia and G-CSF and platelet transfusion for MDS. Although he recovered from pneumonia as neutrophil count increased, intermittent fever continued. On hospital day 17, blood culture yielded fungal colonies indicating S. prolificans. Voriconazole was started immediately, but the man's general condition deteriorated with cerebral infarction and he died of cerebral hemorrhage on hospital day 65. Attention must therefore be paid to the increasing scedosporiosis incidence in Japan.

A 64-year-old man with a 10-year history of Good syndrome had been treated with periodic replacement of γ-globulin. He also had a 6-year history of lichen planus of the tongue. In 2009, the patient was diagnosed as having pure red cell aplasia (PRCA) based on bone marrow aspiration. Thymectomy was not effective. Then, immunosuppressive therapy with PSL and cyclosporine was initiated. Twenty days after treatment painful ulcer appeared on the left side of the tongue. Biopsy specimen of the ulcer demonstrated cells infected with cytomegalovirus and herpes simplex virus. Cytomegalovirus antigenemia was also positive. The tongue ulcer promptly improved after gancyclovir administration for a few weeks. Viral glossitis should be considered as part of the differential diagnoses of oral lesions not only in patients with HIV infection but also in those under immunosuppressive therapy.

An 18-year-old woman was admitted to our hospital with pain in the right upper quadrant of the abdomen and fever. Diagnostic imaging studies, namely, upper gastrointestinal roentogenography and endoscopy, were performed, and an oval cystic tumor was detected in the second part of the duodenum. On the basis of the characteristic findings of the imaging studies and blood tests, we established a definitive diagnosis of duodenal duplication complicated with acute pancreatitis, even before surgical exploration. On surgical examination, the main pancreatic duct appeared to communicate internally with the cystic lesion. The histopathological examination of the surgical specimen confirmed the accuracy of the preoperative diagnosis.

We report a case of 70-year-old man who was admitted to our hospital due to hematemesis in June 2004. He was diagnosed by gastroscopy as having a type III moderately-poorly differentiated adenocarcinoma. A computed tomography (CT) scan revealed multiple lymph nodes swelling (#13, #16), finally he was diagnosed with gastric cancer stage IV (cT3, cN3, cM1). He was treated with S-1, but lymph nodes swelling increased in size, and then in March 2005, the treatment was changed to a second-line chemotherapy consisting of CPT-11 and CDDP. Abdominal CT scan showed a remarkable reduction of #16b1 lymph node, and the second-line chemotherapy was continued until 23 courses. But in April 2007, gastroscopy revealed the enlargement of gastric lesion. He was treated by third-line chemotherapy consisting of paclitaxel and doxifluoridine. This therapy was effective and continued until 7 courses. However, the treatment gradually became resistant and he died in May 2008, which was 4 years since the initial diagnosis.

A 75-year-old man patient was scheduled for total gastrectomy, splenectomy, and cholecyctectomy who had been hypertensive. The patient had no symptoms related to cardiac disease before surgery. Preoperative ECG showed only complete right bundle branch block. After arriving in the operating room, epidural anesthesia was performed at the T8-9 inter space and general anesthesia was induced with propofol without difficulty. Before operation, suddenly PVCs appeared, followed by VT and VF. Immediately the patient was treated with defibrillation, nitroglycerin and nicorandil. The operation was canceled. Vasospastic angina was diagnosed by acetylcholine infusion test postoperatively. Most of patients with vasospastic angina show elevation of ST segment on ECG at first, but our case showed VT and VF without ST elevation on ECG.

A 65-year-old male with IgG-kappa multiple myeloma was treated with melphalan-prednisolone (MP) and obtained a minimal response. Five months after the initiation of MP, he developed back pain, renal failure, hypercalcemia and increased plasma cells in the bone marrow. He was treated with bortezomib. After 2 cycles, he developed a peripheral neuropathy, and the dose of bortezomib was decreased to 1.0 mg/m(2). After 5 cycles, serum monoclonal protein was not detected by immunofixation, and the percentage of bone marrow plasma cells decreased to less than 5%. In March 2007, he developed lumbago again, and MRI of the lumbar vertebrae showed a tumor at the para pediculus arcus vertebrae. Immunohistochemistry of the biopsied tumor demonstrated monoclonal plasma cell infiltration. The patient was treated with local radiation therapy. Bortezomib is a new and effective agent for refractory/relapsed multiple myeloma. It has also been reported that bortezomib is effective for solitary extramedullary plasmacytoma (EMP). However, in the patient reported here, although bortezomib induced a complete response with regard to the serum monoclonal protein and the percentage of bone marrow plasma cells, EMP developed in the parapediculus arcus vertebrae. Herein, we document a case of EMP development during successful bortezomib therapy.

Candida guilliermondii (C. guilliermondii) are uncommon, representing approximately 1% of all Candida infections, but have been reported to show a higher rate of drug-resistance and mortality rate than C. albicans. Current guidelines for treatment of non-albicans candidemia in neutropenic patients now recommend the use of amphotericin B or voriconazole (VRCZ). We describe here the successful treatment for a 58-year-old male with azole-refractory C. guilliermondii fungemia by combination with liposomal (L-AmB) and micafungin (MCFG) therapy. He was diagnosed as having mantle cell lymphoma, and treatment with HyperCVAD (Rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone) was started. Despite prophylactic treatment with fluconazole, he developed fungemia due to C. guilliermondii 41 days after the start of chemotherapy. Positive blood culture and high levels of (1-->3)-beta-D-glucan persisted despite changing the treatment from fluconazole to voriconazole. Although L-AmB was also added to VRCZ, the clinical symptoms worsened. When MCFG was combined with L-AmB, the symptoms and data dramatically improved. Thus, combination therapy consisting of MCFG and L-AmB might be more effective against candidemia that is refractory to azole than combination therapy with VRCZ and L-AmB.

The prognosis of patients with multiple myeloma has been improved in the last decade due to the induction of autologous stem cell transplantation and novel drugs including thalidomide, lenalidomide, and bortezomib into the treatment. Recently, the UK Myeloma Forum and International Myeloma Foundation have successively proposed myeloma management guidelines. Because many novel drugs are not available in Japanese patients, we can not use the same treatment strategy in U.S.A. and Europe. In this chapter, the diagnosis and management guideline is proposed for Japanese patients with myeloma. For convenience, the recommendations are divided into: 1. Diagnostic criteria 2. Indications for starting therapy 3. Treatment(initial therapy, maintenance therapy, and therapy for refractory/relapsed patients) 4. Response criteria 5. Supportive care and management of specific complications.

A 72-year-old woman was referred to our hospital for evaluation of leukocytosis revealed by a medical examination. Her physical examination demonstrated no splenomegaly and no palpable lymph nodes. Her white cell count was 10,900/microl with atypical lymphocytosis (84.5%). Her hemoglobin concentration was 10.4 g/dl, and platelet count 151,000/microl. On peripheral blood smears, the atypical lymphocytes had a hairy cell-like appearance, and phase-contrast microscopic and transmission electron microscopic findings revealed the lymphocytes had many long surface microvilli. Flowcytometric analysis of peripheral blood lymphocytes identified expanded B-lymphocytes as having the IgG+, CD5- CD10- CD11c+ CD19+ CD20+ CD23- CD25- and CD103- cell surface phenotype. Serum electrophoresis disclosed polyclonal elevation of IgG and IgM (2620 mg/dl and 840 mg/dl, respectively). No light-chain restriction and a polyclonal VH gene rearrangement pattern indicated the polyclonal proliferation of B cells. The patient was a nonsmoker and had HLA-DR4, as in previous reports which have suggested an association between hairy B-cell lymphoproliferative disorder (HBLD) and HLA-DR4. No chromosome 3 abnormality was observed. These findings were consistent with the characteristics of HBLD, but differed in some respects from those of persistent polyclonal B-cell lymphocytosis (PPBL). Therefore, we diagnosed this patient as having HBLD.

We present a case of a 74-year-old male, who had a relapse of minimal change nephrotic syndrome (MCNS) as the initial presentation of acquired hemophilia A. MCNS had been maintained in remission with prednisolone 10 mg for 15 years. In early December 2005, the patient developed edema of the right leg, was admitted to a local general hospital, and was diagnosed as having a relapse of MCNS based on massive proteinuria (urine protein 6.1 g/day). One week later, severe anemia (hemoglobin 4.4 g/dl) and acute renal failure (creatinine 2.0 mg/dl) developed, and a CT scan of the abdomen revealed a hematoma in the left iliopsoas muscle. He was referred to our hospital with bleeding tendency. Laboratory examination revealed prolonged APTT 80.5 seconds), reduced factor VIII activity (<1%) and thepresence of factor VIII inhibitor at a titer of 19 Bethesda units/ml, based on which he was diagnosed as having acquired hemophilia A. With recombinant activated FVII, hemostasis was obtained and prednisolone administration 60 mg/day (1 mg/kg) was started. Both the acquired hemophilia A and MCNS responded well to the treatment with prednisolone. Six weeks after initiation of the treatment, factor VIII inhibitor and urine protein disappeared. This patient is considered to be a rare case; to the best of our knowledge, this is the third report of acquired hemophilia A with nephrotic syndrome.

A 51-year-old man visited our hospital because of fever in 2003. With the discovery of the presence of a chest wall tumor, pleural effusion and M-protein, and increased plasma cells in the bone marrow, a diagnosis of multiple myeloma was established. Since the effect of combination chemotherapy followed by tandem auto-PBSCT lasted only one year, thalidomide and dexamethasone administration was started in November 2004. However, three months later, his lower limbs became swollen. Elevation of fibrin degradation product (FDP) and computed tomography findings suggested deep vein thrombosis and pulmonary embolism. With heparin and warfarin, these thromboses disappeared. Furthermore, chemotherapy strategies in addition to thalidomide were safely performed with anti-coagulation therapy. As thalidomide has become an accepted component in therapeutic strategies for multiple myeloma, careful attention must be paid to the prevention of thrombosis.

A 69-year-old house wife admitted to our hospital with complaints of fever, drowsiness, watery diarrhea and uncontrolled blood sugar level. She had been operated for the right mammary carcinoma 11 years ago. Left adrenal mass and nodules in the thyroid gland were discovered by CT and hypersecretion of adrenocortical hormone, catecholamine and PTH as well as ectopic ACTH production were indicated endocrinologically. Autopsy and histopathological examination revealed left adrenal pheochromecytoma associated with bilateral adrenocortical hypertrophy, adenomas in 2 of 5 parathyroid glands and papillary thyroid carcinoma with adenomatous goiter. Ectopic ACTH production was identified immunohistochemically in the pheochromecytoma. This case is a rare variant of non-familial MEN (multiple endocrine neoplasm) type IIA with ectopic ACTH production and metachronous mammary carcinoma.

A 52-year-old woman, height, 149 cm; weight, 40 kg, was admitted because of anterior chest discomfort and palpitations. There was no family history of Marfan syndrome. She had undergone replacement of the ascending aorta and aortic valve 10 years prior for DeBakey II aortic dissection. Postoperative pathological examination of the resected aortic wall revealed cystic medionecrosis. Computed tomography(CT) 4 years after the surgery showed moderate enlargement of the preserved sinuses of Valsalva, and CT 10 years after the surgery showed enlargement of the sinus. She consented to a reoperation. The prostheses were explanted, and the aortic root was replaced with a composite graft. The right coronary artery ostium was completely closed, and no graftable portions of the distal right coronary artery were detected. Thus, the left coronary artery alone was reimplanted. The patient required extracorporeal membrane oxygenation for 10 days postoperatively, after which she recovered fully without complications. This case may indicate that the complete aortic root should be replaced during initial surgery of the ascending aorta or aortic valve in patients with potential risk of sinus of Valsalva dilatation.

A 70-year-old man was referred to our hospital in March 2001 for the purpose of evaluation for anemia and thrombocytopenia. Physical examination revealed hepatosplenomegaly, normal skin, and normal neurologic findings. Blood examination showed a white blood cell count of 10,900/microliter, with a differential count of 58.5% eosinophils and 3.5% blast cells. Flow cytometric analysis of eosinophils revealed that they were positive for CD33, CD13, CD25, and HLA-DR. Bone marrow aspiration could not be performed due to dry tap, and bone marrow core biopsy specimen revealed severe myelofibrosis with blastoid cells proliferation. Cytogenetic analysis of bone marrow cells showed isochromosome 17. FISH analysis using a RAR alpha probe (17q21.1) demonstrated 62% of peripheral blood nucleated cells having three signals. BCR/ABL gene rearrangement by FISH analysis was not observed. Allergic disease, infectious disease, parasitic disease, collagen vascular diseases, pulmonary disease, and neoplastic disorders were excluded. Therefore, a diagnosis of chronic eosinophilic leukemia was made. The patient had no symptoms of hypereosinophilia. However, eosinophils with sparse granulation, positivity for CD25, elevated serum levels of soluble IL-2 receptor, and elevated serum levels of eosinophil cationic protein suggested activation of eosinophils. Further analysis is needed regarding the activation of eosinophils in chronic eosinophilic leukemia.

A 58-year-old HIV-negative woman was admitted to our hospital with abdominal distension. She had a 5-year history of hypothyroidism and a 4-year history of diabetes mellitus. Physical examination revealed ascites. There was no lymphadenopathy or splenomegaly. Laboratory examination showed elevated levels of serum LDH and Al-p, polyclonal hypergammaglobulinemia, and was positive for anti-nuclear antibody, several autoantibodies and HCV-RNA. A computed tomographic scan of the abdomen and chest showed massive ascites, but there was no evidence of tumor masses or lymph node enlargement. Cytologic examination of the ascitic fluid revealed numerous abnormal lymphocytes which by flow cytometry demonstrated expression of CD5, CD19, CD20, and CD4. Cytogenetical analysis demonstrated a hyperdiploid karyotype, with numerical abnormalities. Southern blot analysis demonstrated rearranged monoclonal bands in JH and c-mycgenes. Polymerase chain reaction (PCR) analysis failed to detect the genomes of EBV and HHV-8 in the abnormal lymphocytes. A diagnosis of primary effusion lymphoma of B cell lineage was made. Following abdominal paracentesis, the patient remained in complete clinical remission for 7 months and died of an unrelated cause (cerebral bleeding). The present case demonstrated an HIV-, HHV-8-, and EBV-negative, and HCV-positive primary effusion lymphoma of B cell lineage, with a unique clinical course.

A 65-year-old female who underwent radical mastectomy on 28 April 1988 felt swelling and numbness of her left lower jaw. As a result of bone biopsy and scintigraphy, multiple bone metastasis was diagnosed. After 6 cycles of CMF therapy, the swelling and numbness of the left lower jaw were reduced, but atelectasis of the left lung upper lobe appeared. After 10 cycles of paclitaxel therapy, atelectasis and bone metastasis were reduced. Daily oral chemoendocrine combination therapy, DMpC therapy (5'-DFUR 800 mg/day + CPA 100 mg/day + MPA 800 mg/day) was continued for 12 months. No recurrent signs and serious side effects were observed during DMpC therapy.

Objectives: The concentration of macrophage colony-stimulating factor (M-CSF), an inflammatory cytokine, increases with the progression of coronary lesions, but no clinical investigations have evaluated the relationship to coronary vascular tone. The present study investigated the relationship between M-CSF and vasoreactivity of the coronary arteries in patients with vasospastic angina., Methods: Vasospastic angina (VSA) was characterized by transient chest pain and ischemic ST segment changes at rest, or by a positive result in spasm provocation testing with acetylcholine. The subjects were 24 patients with stable VSA(inactive VSA group) treated on an outpatient basis, 31 VSA patients hospitalized with unstable angina (active VSA group), and 13 healthy subjects(control group). The sensitivity of determination of plasma M-CSF in blood was 40 pg/ml. The levels of this factor in each group were compared. Based on the findings of the acetylcholine vasospasm-induction test, patients were divided into those with single-vessel vasospasm and those with multivessel vasospasm, and, according to the dose of acetylcholine required to induce spasm, into high- and low-dose groups. Plasma M-CSF levels in each group were compared., Results: Mean plasma M-CSF was 598 +/- 180 pg/ml in the inactive VSA group, 775 +/- 194 pg/ml in the active VSA group, and 632 +/- 103 pg/ml in the control group. The mean plasma M-CSF level in the active VSA group was significantly higher than that in the inactive VSA group(p < 0.01). Mean plasma M-CSF level in the single-vessel and multivessel vasospasm groups was highest for active VSA patients with multivessel vasospasm (872 +/- 173 pg/ml). The relationship with the acetylcholine induction dose clarified that plasma M-CSF levels were highest in patients with active VSA in the acetylcholine low-dose group (825 +/- 177 pg/ml, p < 0.001)., Conclusions: Plasma M-CSF concentration reflects the vasoreactivity of coronary spasm in the VSA group, and may be an indicator of the severity of coronary endothelial dysfunction.

We reported a case of a 61-year-old female with arthritis of right knee associated with systemic lupus erythematosus (SLE). She suffered from SLE at age 31 and felt pain around her right knee at age 60. It gradually increased despite intraarticular injections of steroid and arthroscopic synovectomy. On admission, the range of motion of her right knee was 20 to 135 degrees and remarkable gait disturbance were noted due to the pain. Radiographs of the right knee showed joint space narrowing and bone erosion. YMCK total knee arthroplasty was performed. Operation findings showed smooth and thick synovium and cartilage defect. Histological examination revealed fibrin on surface, proliferad connective tissue and newly development of vasculature. Synovium eroded both cartilage and bone. In SLE, soft tissue contructure was reported to be a main cause of joint dislocation, but there were only a few report of progressive joint destruction due to SLE. In this case, the main cause of joint destruction may be invasion synovium into cartilage and bone.

We reviewed 33 patients who underwent a limited operation for primary lung cancer between 1980 and 1998. These cases were divided into three groups; a poor risk group consisting of 18 patients who had a high risk such as pulmonary or cardiac dysfunction and who underwent partial resection of a lung, a reduction group consisting of 9 patients who had advanced lung cancer or uncontrolled cancer of an organ other than the lung and who underwent partial resection, and an active limited operation group consisting of 6 patients who underwent segmentectomy with lymphoadenectomy for the treatment of early lung cancer. The 1 and 3-year survival rates in the poor risk group, reduction group and active limited operation group were 73.9, 60.0, 100%, and 63.4, 0.0, 100%, respectively. The results of limited operations performed for poor risk cases were satisfactory in terms of both functional state and prognosis. Limited operations performed to reduce tumor in advanced lung cancer cases did not improve the prognosis. Although an active limited operation for a case of early lung cancer remains controversial with respect to indication, it is thought that this operation is not inferior to a standard radical operation (lobotomy with mediastinal lymphoadenectomy) in selective cases in which the maximum tumor diameter is 2 cm or less. The indication for a limited operation must be further examined from aspects of tumor size, tumor histology and the other factors of the tumor.

A 70-year-old man was admitted to our hospital because of right hemiparesis. He had no allergies or previous exposure to radiographic contrast medium, and the platelet count on admission was within the normal range. On day 8 of hospitalization, he underwent computed tomography of the brain with 100 ml of iopamidol administered intravenously. Three hours later, his platelet count fell to 5,000/microliter, and he developed purpura. Because drug-induced thrombocytopenia was suspected, platelet transfusion was undertaken and corticosteroids were administered. The platelet count returned gradually to normal in 2 days. At the time, we were unable to ascertain the cause of the thrombocytopenia. To clarify whether the contrast medium had been responsible, iopamidol was added to the patient's heparinized whole blood. Subsequent platelet aggregation was observed microscopically and the platelet count decreased, suggesting that the thrombocytopenia had been due to contrast medium-induced platelet aggregation. Although thrombocytopenia after injection of contrast medium is extremely rare, such cases should be evaluated carefully because the condition can be life-threatening if severe.

An extraction method based on the phase separation of aqueous micellar solutions of n-octyl-beta-D-thioglucoside (OTG) was applied to the concentrating conjugated bilirubin in urine. The analyte in sample solutions could be efficiently concentrated into a small volume of surfactant-rich phase, while hydrophilic matrix components including urinary protein, ascorbic acid, and saccharide remained in the aqueous phase. The concentrated OTG negligibly affected the diazo reaction and the subsequent spectrophotometric detection. Conjugated bilirubin was successfully determined in the concentration range from 0.05 microgram/ml to 5 micrograms/ml with a 96-well microplate reader absorption spectrophotometer.