Lymphoproliferative disorder progressing after partial remission following immunosuppressive drugs withdrawal in a patient with rheumatoid arthritis.

Lymphoproliferative disorders (LPDs) are serious complications that arise in patients with rheumatoid arthritis (RA) receiving immunosuppressive drugs (ISDs). Here, we reported a 73-year-old woman diagnosed with RA at 60 years of age and treated with methotrexate, bucillamine, prednisolone, and infliximab. She was referred to our hospital, Osaka Metropolitan University Hospital, with general malaise, pancytopenia, a right adrenal mass, and enlarged periaortic lymph nodes. Epstein-Barr virus was detected in serum. We suspected LPD development and performed a bone marrow biopsy, on which no malignant cells could be detected. Upon ISDs withdrawal, her symptoms and blood counts improved, and the right adrenal mass and enlarged lymph nodes regressed. The patient was followed up for clinical LPD. However, 7 months after the initial visit to our hospital, she developed fever and pancytopenia. A repeat bone marrow biopsy confirmed the diagnosis of Epstein-Barr virus-positive diffuse large B-cell lymphoma complicated by haemophagocytic syndrome. After pulse steroid therapy, the patient received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone therapy, which resulted in a complete response. In conclusion, when LPDs develop in patients with RA during ISD treatment, LPDs can progress and complicate haemophagocytic syndrome after partial remission following ISDs withdrawal. Therefore, we should carefully follow up RA patients with LPDs, and aim to achieve an early diagnosis of LPD and promptly initiate chemotherapy.

Alendronate inhibits periprosthetic bone loss around uncemented femoral components.

Periprosthetic bone loss can be severe around the femoral component after uncemented arthroplasty. This study investigated the inhibitory effect of alendronate on periprosthetic bone loss. Seventeen patients underwent arthroplasty with an uncemented femoral component. Among them, 8 patients were given alendronate 5 mg once daily for 1 year (ALN group) and 9 patients received no pharmacotherapy (control group). Bone mineral density was measured in six periprosthetic zones by dual-energy X-ray absorptiometry at 1, 6, and 12 months after surgery. The average periprosthetic bone mineral density was 0.674-0.920 g/cm(2) at 1 month after surgery. From 6 months onward, the absolute bone mineral density and the ratio relative to the 1-month value were significantly decreased in the proximal zones of the femur in the control group (the ratio decreased from 0.817 to 0.769; P = 0.0040-0.0353). In the ALN group, however, the absolute and relative bone mineral density of the proximal femur remained unchanged for 12 months. In the other femoral zones, the absolute and relative bone mineral density remained unchanged throughout the study in both groups. We concluded that alendronate significantly inhibited the decrease of periprosthetic bone mineral density in the proximal femur after uncemented arthroplasty.

Effect of endogenously generated nitric oxide on the energy metabolism of peritoneal macrophages.

To understand the role of nitric oxide (NO) in the regulation of cellular metabolism in peritoneal macrophages under physiological low oxygen tension, its effect on the respiration and energy metabolism was examined with casein-induced peritoneal macrophages from the rat. Intraperitoneal injection of casein transiently induced peritoneal infiltration of neutrophils (peaked on day 1) followed by the migration of macrophages that peaked on day 2. Western blotting analysis using antibodies against inducible type of NO synthase (iNOS) revealed that macrophages appeared in the peritoneal cavity during an early stage (approximately day 2) but not during the late stage (day 3 approximately) of inflammation expressed iNOS and generated substantial amounts of NO by a mechanism that was inhibited by N-iminoethyl-L-ornithine (NIO), a specific inhibitor of iNOS. Although NO reversibly but strongly inhibited the respiration of macrophages from both stages particularly under physiologically low oxygen tension, NIO markedly enhanced the respiration of macrophages obtained from the early period but not from the late period of inflammation. The ATP level in the macrophages from the late period but not from the early period was markedly decreased by NO. Biochemical analysis revealed that the glycolytic activity in the macrophages obtained from the early period was significantly higher than that from the late period of inflammation. These results indicate that significant fractions of cellular ATP in iNOS-positive peritoneal macrophages are synthesized by the increased activity of glycolysis particularly under physiological low oxygen tensions where the mitochondrial respiration is strongly inhibited by endogenously generated NO by macrophages and neutrophils.

Glycemic response during exercise after administration of insulin lispro compared with that after administration of regular human insulin.

To examine the glycemic response during exercise after administration of short-acting insulin lispro, we compared changes in plasma glucose concentrations during exercise performed by patients with diabetes after the administration of either insulin lispro or regular human insulin. Seven patients with diabetes (two with type 1 and five with type 2) participated in this study. Each of the insulin-depleted subjects received the same number of units of either insulin lispro or regular human insulin, delivered subcutaneously to the abdomen. The next day, each subject received a similar injection of the solution not previously administered. After each injection, the subjects were fed a standard meal of approximately 9 kcal/kg body weight. One hour after eating the test meal, the subjects performed 30 min of cycle ergometer exercise at 50% maximal oxygen uptake. Plasma glucose, insulin, glucagon, growth hormone (GH), and catecholamine concentrations were then measured at specific intervals. Insulin concentrations were higher and peaked earlier after administration of insulin lispro than after administration of regular human insulin. The length of time, needed to reach minimum plasma glucose concentration after exercise was begun, was significantly shorter after administration of insulin lispro, and the percentage of plasma glucose decrease induced by exercise relative to the peak concentration was significantly greater. No differences were found in the concentration changes of counterregulatory hormones between the insulin lispro data and the regular human insulin data. Compared with regular human insulin, insulin lispro induces a more rapid and greater decrease in plasma glucose concentration during exercise because of its faster absorption.

Impact of diabetes on coronary stenosis and coronary artery calcification detected by electron-beam computed tomography in symptomatic patients.

OBJECTIVE: Ischemic heart disease is a pivotal complication for diabetic patients. Electron-beam computed tomography (EBCT) represents the only noninvasive method that allows for accurate quantification of coronary artery calcification that reflects underlying atherosclerotic disease. Although coronary calcium score (CCS) cut points that predict the presence of angiographic stenosis have been established in nondiabetic individuals, it is not known whether coronary calcifications in diabetic patients are associated with the presence of significant coronary stenoses. In this study, we evaluated the relationship between coronary calcifications and angiographic stenosis in symptomatic patients with or without type 2 diabetes. RESEARCH DESIGN AND METHODS: In this study, 282 patients (204 men and 78 women) with chest pain, including 101 diabetic patients and 181 nondiabetic patients (mean age 63 +/- 9.6 years), underwent coronary angiography and EBCT with determination of CCS using Agatston's method. Luminal stenosis >or= 50% was defined as significant coronary stenosis. RESULTS: Angiography identified 205 patients with significant stenoses (89 of 101 diabetic patients, 114 of 181 nondiabetic patients). The sensitivity and specificity of EBCT to detect significant coronary stenosis were not significantly different between diabetic and nondiabetic patients. In diabetic patients, a CCS >or=90 was associated with 75% sensitivity and 75% specificity, whereas a CCS >or=200 was associated with 64% sensitivity and 83% specificity. CONCLUSIONS: We demonstrated that calcification of the coronary arteries in symptomatic diabetic patients is well associated with severity of coronary stenosis, as in nondiabetic patients.