Evaluation of the pharmacokinetics of linezolid in an obese Japanese patient

We evaluated the pharmacokinetics of linezolid in the case of an obese Japanese patient (body weight 116 kg; body mass index 37 kg/m(2)). Linezolid was administered at a dose of 600 mg by intravenous drip infusion for 60-90 min at 12-h intervals. The results showed increased clearance of linezolid and a reduced serum concentration compared to population pharmacokinetic parameters, with trough levels below the 90% minimum inhibitory concentration. However, linezolid was effective for improving lung infection and inflammation in our patient, which may be due to its particularly effective transfer into lung tissues. Linezolid undergoes slow non-enzymatic oxidation in vivo that may be increased in obese patients, and this may account for the greater clearance. Our findings are useful for the planning of linezolid therapy in obese patients.     

Xanthomatous meningioma: a case report with review of the literature

Xanthomatous meningioma is an extremely rare variant of meningioma that is characterized histopathologically by the presence of tumor cells with lipid-filled vacuolated cytoplasm. In this report, we describe the fifth documented case of xanthomatous meningioma and review its clinicopathological features. A 76-year-old Japanese male presented with dizziness. Magnetic resonance imaging demonstrated a well-circumscribed tumor in the left parasagittal to frontal region with attachment of the dura mater. Histopathological examination of the resected specimen revealed proliferation of polygonal to spindle cells with eosinophilic cytoplasm and bland round to oval nuclei. Whorl formation and psammomas were scattered, and mitotic figures were rarely seen. A peculiar finding was the presence of extensive xanthomatous change continuing to the above-mentioned typical meningothelial meningioma. These tumor cells had clear vacuolated cytoplasm and bland round to oval nuclei. Immunohistochemically, xanthomatous cells were positive for epithelial membrane antigen. Accordingly, an ultimate diagnosis of xanthomatous meningioma was made. Our clinicopathological analysis revealed that xanthomatous meningioma affects children to young persons or the elderly, and four of five cases were located in the supratentorial region. Although the detailed mechanism underlying the xanthomatous change has not been clarified, this change is thought to result from a metabolic abnormality of the neoplastic meningothelial cells. Further, xanthomatous change has also been reported in atypical and anaplastic meningiomas. Therefore, it is important to recognize that xanthomatous change can occur in meningiomas, and to avoid misidentifying these cells as macrophages.     

Adult T-cell leukemia/lymphoma accompanying follicular mucinosis: a case report with review of the literature

Follicular mucinosis is recognized as one of the histopathological reaction patterns characterized by the accumulation of mucin within follicular epithelium. It is induced by various causes including inflammatory diseases, and more than half of the cases are associated with malignant lymphoma, mainly mycosis fungoides. Herein, we describe the third documented case of adult T-cell leukemia/lymphoma (ATLL) accompanying follicular mucinosis. A 72-year-old Japanese male presented with persistent erythema in his arm and neck. Laboratory tests demonstrated positivity for human T-cell leukemia virus (HTLV)-1 antibodies. Histopathological study of the biopsy specimen from the neck revealed superficial perivascular, nodular, and intrafollicular lymphocytic infiltrations. These lymphocytes were small- to medium-sized and had convoluted nuclei. Mucoid material deposition was observed within the hair follicles, and it was digested by hyaluronidase. Immunohistochemically, these lymphocytes were positive for CD3, CD4, CD25, and Foxp3. Accordingly, an ultimate diagnosis of ATLL accompanying follicular mucinosis was made. The skin is the most common extralymphatic site of involvement of ATLL. The present case clearly demonstrated that albeit extremely rare, ATLL can cause follicular mucinosis. Therefore, ATLL should be included in the differential diagnostic consideration of follicular mucinosis.     

Serum immunoglobulin G4 associated with number and distribution of extrapancreatic lesions in type 1 autoimmune pancreatitis patients

Background and Aim: Type 1 autoimmune pancreatitis (AIP) is characterized by the increase of serum immunoglobulin (Ig)G4 and abundant IgG4 plasma cell infiltration in the pancreas and various extrapancreatic lesions (EPL), which are proposed as IgG4‐related disease. We assessed the correlation between serum IgG4 and the number of EPL, and the association between serum IgG4 and the distribution of EPL in type 1 AIP patients. Methods: Serum IgG4 was measured in 35 type 1 AIP patients and 71 non‐AIP patients. The clinical characteristics and distribution of eight EPL were determined in 35 type 1 AIP patients. Results: Serum IgG4 in type 1 AIP was significantly higher than in non‐AIP (P < 0.001). A total of 33 patients had EPL among 35 patients with type 1 AIP (94.3%). There was a significant correlation between serum IgG4 and the number of EPL (ρ = 0.75, P < 0.001). Further, to assess the association between serum IgG4 and the distribution of EPL, type 1 AIP patients were divided into two groups: as abdominal localized EPL and systemic EPL. Both serum IgG4 and total numbers of EPL in systemic EPL were remarkably higher than those in abdominal localized EPL. Serum IgG4 cut‐off value was 346 mg/dL to distinguish between abdominal localized EPL and systemic EPL according to the receiver–operator characteristic curve data. Conclusions: Our findings indicated that serum IgG4 was useful in both the diagnosis of type 1 AIP and the detection of systemic EPL. Our finding may help the concept and diagnostic criteria of IgG4‐related disease with type 1 AIP.     

PTK787/ZK222584 Combined with Interferon Alpha and 5-Fluorouracil Synergistically Inhibits VEGF Signaling Pathway in Hepatocellular Carcinoma

Background

The prognosis of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus remains poor. We previously reported the beneficial effects of interferon alpha (IFN) and 5-fluorouracil (5-FU) combination therapy for these patients. We showed that the mechanism of therapy was regulation of vascular endothelial growth factor (VEGF). Here, we combined IFN/5-FU therapy with the VEGF receptor–selective inhibitor PTK787/ZK222584 (PTK/ZK) and examined the antitumor effects and the mechanism of action.

Methods

We studied two HCC cell lines, PLC/PRF/5 and HuH7, and a human umbilical vein endothelial cell line, HUVEC. We studied the effects of IFN/5-FU with or without PTK/ZK in growth inhibition assays, immunohistochemistry, Western blot analysis, and immunocytochemistry.

Results

In a HuH7 xenograft model, the combination of PTK/ZK and IFN/5-FU significantly inhibited proliferation, induced apoptosis, decreased microvessel density, reduced the number of tumor cells that expressed VEGF receptor 2 (VEGFR-2), and repressed the phosphorylation of Akt in vivo. In HCC cells and HUVECs in vitro, IFN/5-FU plus PTK/ZK repressed the expression of VEGFR-2 and repressed the phosphorylation of VEGFR, Akt, Erk, and p38MAPK.

Conclusions

VEGF signaling inhibition enhanced the antitumor effects of IFN/5-FU therapy on HCC cells and endothelial cells via Erk, Akt, and p38MAPK pathways.