Community-acquired pneumonia (CAP) continues to be a major medical problem. Since CAP is a potentially fatal disease, early appropriate antibiotic treatment is vital. Epidemiologic studies have shown that in the combined cause-of-death category, pneumonia ranks fourth as the leading cause of death in Japan. Therefore, the Japanese Respiratory Society (JRS) provided guidelines for the management of CAP in adults in 2000. Because of evolving resistance to antimicrobials and advances in diagnosis, treatment and prevention of CAP, it is felt that an update should be provided every three years so that important developments can be highlighted and pressing questions can be answered. Thus, the guidelines committee updated its guidelines in 2005. The basic policy and main purposes of the JRS guidelines include; 1) prevention of bacterial resistance and 2) effective and long-term use of medical resources. The JRS guidelines have recommended the exclusion of potential and broad spectrum antibiotics, fluoroquinolones and carbapenems, from the list of first-choice drugs for empirical treatment. In addition, the JRS guidelines have recommended short-term usage of antibiotics of an appropriate dose and pathogen-specific treatment using rapid diagnostic methods if possible.

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Background: α-melanocyte-stimulating hormone (α-MSH), a pro-opiomelanocortin (POMC) derivative, is a neuropeptide with potent anti-inflammatory properties that inhibits tissue injury in a wide array of inflammation models.
Objective: To determine if α-MSH is involved in the development of congestive heart failure (CHF) with the specific aim of examining its peripheral source and one of the mechanisms.
Methods: The circulating levels of α-MSH were measured in 115 patients with CHF using a double-antibody radioimmunoassay. To determine one of the sources of circulating α-MSH, human peripheral blood mononuclear cells (PBMC) were stimulated with lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-α. Furthermore, to clarify one of the functions of α-MSH, PBMC were cultured in the presence or absence of α-MSH.
Results: Plasma levels of α-MSH were significantly higher in NYHA class II patients with CHF than in control subjects (p<0.0001). A significant correlation was found between the levels of α-MSH and high-sensitive testing for C-reactive protein in patients with CHF (r=0.41, p<0.0005). PBMC stimulated with LPS or TNF-α released α-MSH in a concentration-dependent manner. α-MSH inhibited LPS-induced TNF-α production, and α-MSH simultaneously augmented production of interleukin (IL)-10 by PBMC.
Conclusions: Circulating α-MSH was increased in patients with CHF. Inflammatory response induced α-MSH production in cultured human PBMC. Treatment of α-MSH could modify the immunobalance between inflammatory and anti-inflammatory responses in cultured PBMC. These findings suggest that α-MSH may play an important role in the pathophysiology of CHF.

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Objective: The receptor for advanced glycation end-products (RAGE) is one of several advanced glycation end-product (AGE)-specific cellular receptors. To evaluate the relationship between AGE and RAGE in renal tissues of diabetic nephropathy (DN), we examined the levels of expression of AGE protein and of RAGE mRNA. We also investigated the relationships among the degree of mesangial expansion and the expression of AGE and RAGE mRNA.
Patients and Methods: Renal biopsy tissues were obtained from 20 patients with DN. We performed immunohistochemical staining using monoclonal anti-AGE antibody and in situ hybridization using non-radioactive oligonucleotide RAGE probe on these tissues. We also examined five control renal samples. We evaluated the intensity of positive anti-AGE antibody staining and the percentage of cells positive for RAGE mRNA. We also measured the total glomerular area and mesangial area in glomeruli using an automatic image analyzer. We then calculated the percentage of mesangial area as a proportion of the total glomerular area (%Mes).
Results: Anti-AGE antibody was detected in the expanded mesangial matrix in DN but not in control samples. RAGE mRNA expression was detected mainly in glomerular intrinsic cells, including glomerular mesangial and epithelial cells, in both DN and control. %Mes correlated significantly with both the intensity of anti-AGE antibody positive staining and the percentage of cells positive for RAGE mRNA.
Conclusions: Our findings suggest that both AGE and RAGE are associated with the development and progression of DN.

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Objective: The authors identified a patient with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), who completely fulfilled the clinical criteria with low thymidine phosphorylase (TP) activity. However, the same homozygotic S471L TP gene mutation was also found in her unaffected mother, but with normal TP activity. To elucidate the pathogenesis of MNGIE, we performed the analysis below.
Methods: We analyzed the TP gene mutation in the proband and 145 unrelated individuals by direct sequence and restriction fragment length polymorphism (RFLP). TP activity was determined by the spectrophotometric method for each TP S471L genotype.
Results: Among 145 normal persons, the S471L homozygote mutants were identified in 2.76% and their enzyme activity was normal.
Conclusion: TP gene mutation is not a primary cause of MNGIE, but with a mitochondrial deletion mutation, a single nucleotide polymorphism (SNP) of the TP gene may be crucial in the pathogenesis of MNGIE.

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Background: Treatment for acute ischemic stroke should be administered as soon as possible after symptom onset. The aim of this study was to investigate whether or not the patient's and bystander's first impression at stroke onset was associated with hospital arrival time.
Methods: To investigate the factors influencing the prehospital delay, we prospectively interviewed consecutive stroke patients and bystanders about their first impression at the stroke onset and assessed the methods of transportation, and clinical characteristics. Early arrival was defined as a hospital arrival of within 2 h from stroke onset.
Results: One hundred thirty patients were enrolled: 82% were ischemic stroke and 18% were cerebral hemorrhage. The median interval between symptom onset and the hospital arrival was 7.5 h and 30% of patients presented within 2 h of stroke onset. First impression of stroke (odds ratios [OR] 4.56, 95% confidence interval [CI] 1.54-13.5, p=0.006), presence of consciousness disturbance (OR 4.29, CI 1.39-13.3, p=0.011), arrival through other facilities (OR 0.25, CI 0.08-0.76, p=0.015), a history of diabetes (OR 0.23, CI 0.06-0.80, p=0.028) and nocturnal onset (OR 0.19, CI 0.04-0.88, p=0.042) independently contributed to the early arrival.
Conclusions: The first impression of patients and bystanders at stroke onset is important in order to reach hospital earlier in Japan. Public educational systems such as those, which advertise stroke warning signs, are necessary

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Objective: To determine the effective dose of cabergoline in Japanese patients with restless legs syndrome (RLS).
Methods: Six cases of idiopathic RLS and three of RLS with Parkinson disease (PD) participated in an open clinical preliminary trial. All cases were diagnosed based on the clinical criteria of the International RLS Study Group. Three RLS cases (1.3%) were detected out of 229 consecutive cases with PD. RLS severity was evaluated with International RLS Study Group (IRLSSG) Rating Scale Version 2.2 before and one year after the treatment with cabergoline.
Results: For 6 idiopathic RLS patients, the IRLSSG questionnaire scores improved from 25.5±3.7 to 10.7±8.9 (p=0.028, Wilcoxon test) with 1 mg of daily cabergoline at the endpoint. For 3 RLS cases with PD, the score was 21.7±3.7 before the treatment, and RLS symptoms completely disappeared with 1 mg of cabergoline. One of RLS cases with PD required additional cabergoline later because of parkinsonism. No adverse event with cabergoline was reported in this study.
Conclusion: One mg of daily cabergoline is effective in some Japanese patients of RLS.

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A 65-year-old woman was admitted to our hospital due to palpitation. Electrocardiogram (ECG) showed ventricular tachycardia originating from the right ventricle, and transthoracic echocardiography revealed dilatations of the right atrium and ventricle. The diagnosis of arrhythmogenic right ventricular cardiomyopathy was made. Eleven months later, echocardiography revealed a solid thrombus (36×32 mm) attached to the free wall of the right atrium, and it was surgically resected. Four months after the operation, a solid thrombus (48×30 mm) appeared again at the same site despite anticoagulant treatment. The patient died of both left and right heart failure 33 months after the operation.

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A 70-year-old man who had been diagnosed with retroperitoneal fibrosis (RPF) was admitted to our hospital complaining of dyspnea. Imaging studies showed massive pericardial effusion. His condition deteriorated and pericardiostomy was performed. A biopsy of the pericardium revealed marked fibrosis with infiltration of lymphocytes, which was identical to RPF findings. A diagnosis of multifocal fibrosclerosis was made. Despite aggressive treatment, he died with clinical signs of cardiovascular failure. The autopsy specimen revealed proliferation of fibrosis with infiltration of lymphocytes in multiple organs. Even after successful decompression of urinary obstruction for RPF, long-term follow-up is necessary in these patients because of the possibility of other fatal complications such as pericardial fibrosis.

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A 70-year-old man with alcoholic cardiomyopathy underwent ^99mtechnetium-sestamibi (MIBI), iodine-123-labeled metaiodobenzylguanidine (MIBG) scintigraphy and Iodine-123-labeled beta-methyl-iodophenyl pentadecanoic acid (BMIPP) scintigraphy. ^99mTechnetium-MIBI identified myocardial damage in the inferior wall of left ventricle. ¹²³I BMIPP showed low uptake in the inferior wall of the myocardium, concordant to perfusion. ¹²³I BMIPP and ¹²³I MIBG showed reduced uptake in the inferior segment of the myocardium, indicating impairment of fatty acid metabolism and sympathetic abnormalities. Damaged myocardium was demonstrated in alcoholic cardiomyopathy. Beta blocker (carvedilol) and angiotensin-receptor blocker (valsartan) were started at low doses, then increased gradually, leading to the improvement of cardiac performance. Cardiac sympathetic nerve function, impaired due to alcoholic cardiomyopathy, was improved with beta-blocker therapy. Cardiac scintigraphy may be useful to assess the extent of myocardial improvement and the response to therapy.

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We present a case of rapid onset of glycogen storage hepatomegaly, caused by a massive dose of long-acting insulin and large doses of glucose, in a type-2 diabetic patient. A 41-year-old man was admitted to our hospital because of hypoglycemia and unconsciousness following subcutaneous administration of 180 units of insulin glargine in a suicide attempt. Despite continuous hypercaloric infusion with additional intravenous glucose injections, hypoglycemia persisted for 36 hours. Although the hepatic function was normal and no hepatomegaly was detected on admission, the liver function tests became abnormal and hepatomegaly was detected on hospitalization day 3. Plain abdominal computed tomography (CT) scanning confirmed liver enlargement, with hepatic CT attenuation markedly elevated at 83.7 HU. Liver biopsy revealed hepatocytic glycogen deposition with edematous degeneration. Based on these findings, the diagnosis was made as rapid onset glycogen storage hepatomegaly caused by administration of a massive dose of long-acting insulin and supplementation with large doses of glucose. With improved glycemic control, the liver function improved, the CT findings of hepatomegaly improved, and the hepatic CT attenuation decreased. Repeat liver biopsy also confirmed almost complete disappearance of glycogen deposits. When hepatic dysfunction or hepatomegaly is detected during treatment with insulin, the possibility of hepatic glycogen deposition should be considered. CT scanning and liver biopsy were useful in diagnosing this case.

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A 31-year-old man referred to our hospital for treatment of his chronic myeloid leukemia (CML) in the first chronic phase by bone marrow transplantation. We pretreated him with cyclophosphamide and total body irradiation and bone marrow transplantation (BMT) was carried out. On day 31, the engraftment was confirmed and on day 52, acute graft versus host disease (GVHD) was observed. On day 189, he lost consciousness due to cyclosporine A-induced leukoencephalopathy and 375 mg cyclosporine A was changed to 100 mg prednisolone. On day 199, liver dysfunction (AST 410 IU/L, ALT 557 IU/L, γGTP 385 IU/L, ALP 363 IU/L, D-Bil 0.3 mg/dl) developed and a liver biopsy was performed. PCR analysis of DNA from the liver biopsy specimen was positive for HHV-6 and immunostaining using anti-HHV-6 and anti-HHV-6b antibodies showed positive staining in the cytosol of hepatocytes. No other viruses were found to induce hepatitis. From these results, he was diagnosed as having HHV-6 hepatitis and it was successfully treated with gancyclovir (GCV) administration.

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We report a case of myasthenia gravis (MG) associated with autoimmune thrombocytopenic purpura (AITP) and autoimmune hemolytic anemia (AIHA), and after that gastric cancer appeared. A 51-year-old man began to suffer from fluctuated muscle weakness in 1985. Muscle weaknesses became exacerbated, and he was admitted to our hospital in 1989. He was diagnosed as MG associated with AITP. After a thymectomy (hyperplasia), prednisolone therapy was started, subsequently his condition was satisfactory. In March 1995, he developed severe anemia and icterus. He was diagnosed as Evans' syndrome (AIHA and AITP) with MG. High-doses of immunoglobulin administration improved the anemia, but thrombocytopenia continued. In November 2002, he suffered marked petechia; the platelet count decreased to 1000/μl. Methylprednisolone pulse therapy and platelet transfusion were started. Gastrofiberscopy was performed and biopsy specimens revealed signet cell-type adenocarcinoma. On December 19, 2002, subtotal gastrectomy and splenectomy were performed. After that, his condition has remained satisfactory, without MG symptoms or thrombocytopenia. This is the first such case report in the literature.

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