Therapeutic Dilemma of Sarcoidosis and Treatment-naïve Hepatitis C Manifesting as Tattoo Reactions

A 23-year-old man had an 8-day history of fatigue and dry cough and papulo-nodular reactions on his extensive tattoos. Chest radiography revealed several small granular shadows, and a transbronchial lung biopsy showed non-caseating epithelioid cell granuloma. A skin biopsy of the tattooed area showed histiocytic infiltrates with phagocytized tattoo pigment. Antibody tests for hepatitis C virus were positive. The patient was successfully treated with corticosteroid therapy, and after inflammation was suppressed, he received delayed anti-viral therapy. Sarcoidosis should be considered as a concurrent condition if papules are presented on the tattoos of patients with hepatitis C.     

Mechanism of cytotoxicity of 5-fluorouracil: Distinction between the irreversible cytotoxic effect of 5-fluorouridine and the reversible cytotoxic effect of 5-fluoro-2′-deoxyuridine on murine lymphoma L5178Y cells in culture

Summary To determine the relative importance of the DNA and RNA effects in the cytotoxicity of 5-fluorouracil, we determined the effects of brief exposure to 5-fluorouridine and 5-fluoro-2-deoxyuridine, compared with 5-fluorouracil, on the subsequent growth of murine lymphoma L5178Y cells during prolonged incubations following the removal of the drug from the culture medium. 5-Fluoro-2-deoxyuridine markedly inhibited cell proliferation by continuous exposure. However, its inhibitory effect by exposure even at 1,000 M for 1 h easily disappeared within 1 week after removal of the drug from the culture medium. This result indicates that the cytotoxic effect of 5-fluoro-2-deoxyuridine is reversible on cell proliferation.On the other hand, the exposure to 5-fluorouridine, event at the low concentration of 1.5 M for 1 h, caused a substantial and irreversible inhibition on cell proliferation.The cytotoxic effect of 5-fluorouracil was also an irreversible action similar to that of 5-fluorouridine.Abbreviations FU 5-fluorouracil - FUR 5-fluorouridine - FUdR 5-fluoro-2-deoxyuridine - IC₉₉ 99% inhibition concentration     

Plasma leptin concentrations are associated with bone mineral density and the presence of vertebral fractures in postmenopausal women

OBJECTIVE: Although total fat body mass (FM) is considered to be one of the major determinants of bone mass, the mechanism by which FM and bone mass are positively correlated remains unclear. Leptin, the product of the obese (ob) gene, is secreted from adipocytes and its plasma levels are known to be positively correlated with %fat (FM divided by total body weight). There is recent evidence suggesting that leptin directly stimulates osteoblastic differentiation. Thus it is possible that the anabolic action of this hormone on bone may participate in the positive correlation between FM and bone mass. In this study, we analysed the relationships between either plasma leptin levels or %fat vs. bone mineral density (BMD) values as well as the presence of vertebral compression fractures, and evaluated whether or not plasma leptin levels were associated with BMD or bone fragility in a manner independent of FM. PATIENTS: One hundred and thirty-nine postmenopausal women (age 48-78 years, mean 62.5), who visited our outpatient clinic for the evaluation of osteoporosis. DESIGN AND MEASUREMENTS: Plasma concentrations of leptin after an overnight fast were measured by radioimmunoassay. BMD values were measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine, femoral neck and whole body. Distal one-third of radius BMD was measured by single photon absorptiometry (SPA). Vertebral fractures were assessed by lateral thoracic and lumbar spine radiographs. RESULTS: Although neither plasma leptin levels nor %fat correlated with age, there was a significant positive correlation between plasma leptin levels and %fat (r = 0.563, P < 0.001). Plasma leptin levels were significantly and positively correlated with BMD values at all skeleton sites measured, and multiple regression analysis revealed that this positive relationship was still observed with BMD values of the femoral neck and of the whole body, even after %fat and age were taken into account. Moreover, plasma leptin levels but not %fat were significantly lower in women with vertebral fractures than in those without fractures. When multiple logistic regression analysis was performed with either plasma leptin value or %fat employed as independent variables, plasma leptin values but not %fat were selected as an index affecting the presence of vertebral fractures. CONCLUSION: Our study showed that plasma leptin levels but not %fat are associated with BMD and the presence of vertebral fractures in postmenopausal women, suggesting that circulating leptin might play a physiological role in maintaining bone mass as well as better bone quality.     

Sclerosing mesenteritis: A real manifestation or histological mimic of IgG4‐related disease?

We present three cases of sclerosing mesenteritis and review the literature to learn whether or not sclerosing mesenteritis is an IgG4‐related disease (IgG4‐RD). Our patients were all adult males. Their mesenteric masses ranged from 6.5 to 14.5 cm in the greatest diameter. Tissue specimens showed moderate to severe lymphoplasmacytic infiltration with occasional eosinophils against a background of irregular fibrosis. Both obliterative phlebitis and storiform fibrosis were noted in all cases. IgG4+ plasma cells were moderately increased in number (46 to 85 cells/high‐power field). However, unlike IgG4‐RD, the IgG4+/IgG+ plasma cell ratio was <40% (28% to 35%). Serum IgG4 concentrations were also within the normal range (43.2 to 105 mg/dL; normal range <135 mg/dL). Two biopsy cases showed spontaneous regression on imaging approximately 5 months later. No sclerosing conditions were found in other organs. The literature review identified 11 additional cases of sclerosing mesenteritis with IgG4+ plasma cell infiltration. However, conclusive cases with four characteristic features (high serum IgG4 levels, tissue IgG4 elevation, multi‐organ involvement, and effective response to glucocorticoid therapy) have never been reported. In conclusion, although sclerosing mesenteritis shares histological features with IgG4‐RD, most cases are less likely to be IgG4‐related. IgG4‐RD seemingly seldom, if ever, affects this anatomical site.     

In vitro and in vivo Effects of Cisplatin and Etoposide in Combination on Small Cell Lung Cancer Cell Lines

The effects of cisplatin (CDDP) and etoposide (ETP) in combination were evaluated in vitro and in vivo using small cell lung cancer cell lines. The combination effects in vitro were investigated using isohologram analysis. Used together, CDDF and ETP showed a synergistic effect against cell growth on only 1 cell line (SBC-3), additive effects on 6 (SBC-2, SBC-5, Lul30, Lul34AH, Lul35T and H69) and an antagonistic effect on 1 (SBC-1). In the in vivo experiment, nude mice were inoculated with SBC-1, SBC-3 and SBC-5 cells. Two or 5 mgAg CDDP and 10 or 30 mgAg ETP were administered intraperitoneally alone and simultaneously in combination to nude mice. The in vivo effects of the combination were determined by comparing the observed growth ratio in mice treated with the combination with the expected value of this ratio calculated based on the assumption that the effects of the drugs were simply additive. According to this definition, synergistic effects were observed against all 3 tumors. Thus, the in vivo and in vitro effects differed. The toxicity of the combination therapy, which was analyzed by estimating the body weight change of mice, was no higher than that of CDDP or ETP alone. These results suggest that the excellent clinical effects of CDDP and ETP combination therapy may he attributable not to drug interaction at the cellular level hut to the feasibility of combined use of them at full doses without overlapping side effects.