In LEW rats treated daily with variable doses of FK506 for 14 days and weekly thereafter, successful intestinal transplantation from fully allogeneic BN donors never was complicated by fatal GVHD. In contrast, with LEW-to-BN transplantation, rejection was difficult to control and GVHD developed after the end of the daily treatment. However, FK506 in high daily doses continued after the initial 14-day course could prevent this GVHD or even reverse it after allowing its onset. Further experiments did not clarify why the BN rat was an "easy" donor and "difficult" recipient. In unaltered animals the lymphocyte population of normal LEW rats had a higher proportion of T cells, fewer B cells, and a lower CD4:CD8 ratio than normal BN rats. However, one-way MLR reactions of the BN and LEW combinations were generally similar in either direction and not affected differently by the addition of FK506 to the medium. The two-way lymphocyte traffic from graft to host lymphoid organs and vice versa also was similar with BN-to-LEW and LEW-to-BN models. The BN rat may be a useful tool to investigate inadequately explained mechanisms of GVHD.
Plasma diafiltration (PDF) is a blood purification therapy in which simple plasma exchange (PE) is performed using a selective membrane plasma separator while the dialysate flows outside the hollow fibers. A prospective, multicenter study was undertaken to evaluate the changes in bilirubin, IL-18, and cystatin C, as well as the 28-day and 90-day survival rates, with the use of PDF according to the level of severity as measured by the Model for End-Stage Liver Disease (MELD) score. Twenty-one patients with liver failure were studied: 10 patients had fulminant hepatitis and PDF therapies were performed 28 times; 11 had acute liver failure with the therapy performed 96 times. Levels of total bilirubin, IL-18, and cystatin C decreased significantly after treatment. The 28-day survival rate was 70.0% and that at 90 days was 16.7%. According to the severity of the MELD score, each of the results compared well with the use of Molecular Adsorbent Recirculating System or Prometheus therapy. In conclusion, PDF appears to be one of the most useful blood purification therapies for use in cases of acute liver failure in terms of medical economics and the removal of water-soluble and albumin-bound toxins.
We report two cases of hypertriglyceridemic necrotizing pancreatitis treated by plasma exchange (PE). The outcome of each case was quite different according to the timing of PE. A 36 year old man presented with abdominal pain, and a diagnosis of severe acute pancreatitis was made. His serum triglyceride (TG) level was 6,460 mg/dl. He did not undergo PE at first, however, his condition never improved and PE was performed 20 days after the onset of his illness. Finally, he died of multiple organ failure and sepsis. In contrast, a 52 year old man with acute necrotizing pancreatitis was referred to our department.He received PE quickly after hospital admission. His serum TG level, which was 3,540 mg/dl at hospital admission, dramatically returned to normal limits, and he was discharged from the hospital 62 days after admission. The prognosis of severe necrotizing pancreatitis due to hypertriglyceridemia is extremely poor. PE should be applied for the treatment of hypertriglyceridemic necrotizing pancreatitis immediately after its onset.
Hemodialysis patients with diabetic kidney disease (DKD) experience blood glucose fluctuations owing to insulin removal. We evaluated the effects of single and long-term application of neuromuscular electrical stimulation (NMES) during hemodialysis on glycemic control. This trial was conducted in two stages: Stage 1, following a crossover design and 4 week washout period, eleven outpatients with DKD either underwent a single bout of NMES for 30 min (NMES period) or rested (control period) after receiving nutritional support during hemodialysis; Stage 2, following a crossover design and 4 week washout period, each participant received the intervention for 12 weeks. NMES was administered for 30 min at the maximum tolerable intensity. The mean subcutaneous glucose concentration and mean amplitude of glycemic excursion (MAGE) were determined by flash glucose monitoring for 24 h. Changes in glycoalbumin and MAGE before and after NMES initiation were evaluated. The mean blood glucose level and MAGE after a single bout of NMES were significantly lower than those after rest. Glycoalbumin levels and echo intensity of the rectus femoris tended to decrease, but not significantly by ANOVA due to a lack in statistical power after the dropout of three patients. NMES in end-stage DKD decreased blood glucose levels during and after hemodialysis.
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