Mediastinal lymphadenopathy without cervical lymphadenopathy in a case of Kikuchi-Fujimoto disease.

A 44-year-old man was referred to our hospital because of persistent high fever. Both CT and PET-CT demonstrated lymph node lesions limited to the mediastinal region without cervical lymphadenopathy. Histology of a mediastinal lymph node obtained by video-assisted thoroscopic excision confirmed the diagnosis of histiocytic necrotizing lymphadenitis. To our knowledge, this is the first report of Kikuchi-Fujimoto disease with isolated mediastinal lymphadenopathy. Although Kikuchi-Fujimoto disease is rare, we should consider this disease in patients with a high fever and no other symptoms.

Involvement of endotoxin in the mortality of mice with gut-derived sepsis due to methicillin-resistant Staphylococcus aureus.

MRSA causes a wide diversity of diseases, ranging from benign skin infections to life-threatening diseases, such as sepsis. However, there have been few reports of the pathophysiology and mechanisms of sepsis resulting from the gut-derived origin of MRSA. Therefore, we established a murine model of gut-derived sepsis with MRSA and factors of MRSA sepsis that cause deterioration. We separated mice into four groups according to antibiotic treatment as follows: (i) ABPC 40 mg/kg; (ii) CAZ 80 mg/kg; (iii) CAZ 80 mg/kg + endotoxin 10 microg/mouse; and (iv) saline-treated control groups. Gut-derived sepsis was induced by i.p. injection of cyclophosphamide after colonization of MRSA strain 334 in the intestine. After the induction of sepsis, significantly more CAZ-treated mice survived compared with ABPC-treated and control groups. MRSA were detected in the blood and liver among all groups. Endotoxin levels were significantly lower in the CAZ-treated group compared to other groups. Inflammatory cytokine levels in the serum were lower in the CAZ-treated group compared to other groups. Fecal culture showed a lower level of colonization of E. coli in the CAZ-treated group compared to other groups. In conclusion, we found that CAZ-treatment ameliorates infection and suppresses endotoxin level by the elimination of E. coli from the intestinal tract of mice. However, giving endotoxin in the CAZ-treated group increased mortality to almost the same level as in the ABPC-treated group. These results suggest endotoxin released from resident E. coli in the intestine is involved in clinical deterioration resulting from gut-derived MRSA sepsis.

Interleukin-1 deficiency in combination with macrophage depletion increases susceptibility to Pseudomonas aeruginosa bacteremia.

We evaluated the role of IL-1 during Pseudomonas aeruginosa bacteremia by intravenously injecting P. aeruginosa strain D4 into IL-1-deficient and WT mice. The two strains showed equivalent mortality rates. However, when the mice were pretreated with cyclophosphamide, bacteremia-induced mortality was significantly greater in the IL-1-deficient mice than in the WT mice (P < 0.01). We then investigated the role of neutrophils and macrophages in protecting IL-1-deficient mice from bacteremia by administering anti-Gr-1 antibody or liposomes containing dichloromethylene diphosphonate, respectively. After P. aeruginosa inoculation survival was significantly lower in the macrophage-depleted IL-1-deficient mice than in the WT mice. In contrast, neutrophil depletion did not have this effect. Compared to the macrophage-depleted WT mice, the macrophage-depleted IL-1-deficient bacteremic mice had higher bacterial counts in various organs 48 and 72 hr post-infection. They also had lower TNF-alpha, IL-6, and INF-gamma concentrations in their livers during the early phase of sepsis. Thus, IL-1 deficiency becomes disadvantageous during P. aeruginosa bacteremia when it is accompanied by immunosuppression, particularly when macrophage functions are seriously impaired.

Impaired consciousness caused by a metastatic adrenal tumor of pulmonary adenocarcinoma.

We report a case of pulmonary adenocarcinoma metastasizing to the adrenal glands, which caused adrenal insufficiency leading to impaired consciousness. A 62 year-old man was admitted with impaired consciousness. The patient started chemotherapy from 2004 for pulmonary adenocarcinoma. In August 2004, a metastatic adrenal tumor was detected and chemotherapy was continued thereafter. From July 2005, the patient started to have mild hyperkalemia, anorexia and general malaise, which progressed to disturbance of consciousness. At admission, physical examination showed generalized pigmentation in the skin and mucosa. Blood test revealed hypoglycemia, hyponatremia and hyperkalemia. A dexamethasone suppression test and a rapid ACTH loading test led to a diagnosis of primary hypoadrenalism (Addison's disease). Treatment with hydrocortisone improved the physical status and blood test values. However, the patient subsequently died of disseminated intravascular coagulation due to the tumor.

Role of galectin-3 in human pulmonary fibrosis.

BACKGROUND: Galectin-3 is a beta-galactoside-binding protein which is implicated in diverse physiological and pathological processes including human liver cirrhosis and a mouse lung fibrosis model. The aim of this study is to determine whether galectin-3 is involved in human lung fibrosis. METHODS: We measured galectin-3 concentration in bronchoalveolar lavage fluid (BALF) and examined its expression in alveolar macrophages from patients with interstitial lung disorders using ELISA and immunohistochemical staining, respectively. Using monocyte/macrophage cell lines in vitro, we examined the effect of cytokines on galectin-3 expression, and the opposite similarly by RT-PCR and Western blotting. Finally, we performed Micro Boyden chamber assay and Sircoll assay to determine whether galectin-3 induces migration and collagen synthesis, respectively, in fibroblasts. RESULTS: Galectin-3 was specifically increased in BALF from patients with idiopathic pulmonary fibrosis (IPF) and interstitial pneumonia associated with collagen vascular disease (CVD-IP). Galectin-3 levels in BALF seemed to be lower in IPF and CVD-IP patients receiving corticosteroid therapy. Alveolar macrophages from IPF patients expressed more galectin-3 compared with those from control. Galectin-3 expression was induced by tumor necrosis factor-alpha (TNF-alpha) and interferon (IFN)-gamma in a monocytic cell line U937. Galectin-3 also induced mRNA expression and protein production of TNF-alpha and interleukin (IL)-8 in a macrophage cell line THP-1. This lectin stimulated NIH-3T3 fibroblast to induce migration and collagen synthesis in vitro. CONCLUSIONS: These results suggest that galectin-3 is involved in the pathogenesis of human IPF and CVD-IP by activating macrophages and fibroblasts.

[Successful chemotherapy with carboplatin and docetaxel for an elderly patient with advanced non-small cell lung cancer].

A 79-year-old man was admitted to our hospital with right hypochondrium pain. His chest X-ray and CT scan showed a mass lesion on the left upper lobe, and multiple metastases in the liver. The diagnosis was non-small cell carcinoma of the lung. He received 4 courses of combined chemotherapy of carboplatin and docetaxel every 4 weeks. At the end of 4 courses, a partial response was achieved. Two courses of a in similar regimen were added at the time of a later recurrence, and the effect was a partial response. Carboplatin+docetaxel combined chemotherapy, which can be conducted relatively safely on an outpatient basis, may be an effective treatment for non-small cell lung cancer in the elderly.

Interleukin-1-deficient mice exhibit high sensitivity to gut-derived sepsis caused by Pseudomonas aeruginosa.

BACKGROUND: The role of interleukin (IL)-1 in infectious diseases is controversial; some investigators indicated an enhancing effect of IL-1 on host resistance whereas others demonstrated the protective role of IL-1 receptor antagonist in infection. We evaluated the role of endogenous IL-1 in gut-derived sepsis caused by Pseudomonas aeruginosa, by comparing IL-1-deficient mice and wild-type (WT) mice. METHODS: Gut-derived sepsis was induced by intraperitoneal injection of cyclophosphamide after colonization of P. aeruginosa strain D4 in the intestine. RESULTS: The survival rate of IL-1-deficient mice was significantly lower than that of WT mice (P<0.01). Bacterial counts in the liver, mesenteric lymph node and blood were significantly higher in IL-1-deficient mice than in WT mice. Tumor necrosis factor alpha and IL-6 in the liver were significantly higher in IL-1-deficient mice than in WT mice. In vitro, phagocytosis and cytokine production by macrophages were impaired in IL-1-deficient mice compared with WT mice. CONCLUSION: Our results indicate a critical role for IL-1 during gut-derived P. aeruginosa sepsis. The results also suggest that both impairment of cytokine production and phagocytosis by macrophages are caused by IL-1 deficiency and lead to impaired host response.

Compensatory response of IL-1 gene knockout mice after pulmonary infection with Klebsiella pneumoniae.

This study was designed to determine the role of interleukin (IL)-1 in the inflammatory response against experimentally induced pneumonia caused by Klebsiella pneumoniae. The host immune responses of IL-1 gene knockout (IL-1 KO) mice and immunocompetent wild-type (WT) mice were compared after pulmonary infection with K. pneumoniae. There were no significant differences between the survival rates and viable bacterial counts in lungs and blood of IL-1 KO and WT mice after pulmonary infections under different conditions. Histopathological analysis showed a similar inflammatory response in both groups of mice. However, in the early stage of infection, the level of tumour necrosis factor alpha (TNF-alpha) in homogenized lungs of IL-1 KO mice was significantly higher than in WT mice. To determine the role of endogenous TNF-alpha in the recovery of the defence mechanism in IL-1 KO mice, mice were treated with an anti-TNF-alpha mAb before infection with K. pneumoniae. The results revealed a significantly lower survival rate of anti-TNF-alpha mAb-treated IL-1 KO mice than BSA-treated IL-1 KO mice. The data suggest that compensatory production of TNF-alpha in IL-1 KO mice contributes to the host defence against K. pneumoniae infection.