Therapeutic Effect of Sirolimus for Lymphangioleiomyomatosis Remaining in the Abdominopelvic Region After Lung Transplantation: A Case Report.

PURPOSE: Sirolimus (SRL) is used to treat pulmonary lymphangioleiomyomatosis (P-LAM). There is limited evidence that SRL has systemic efficacy for the patients with extrapulmonary lymphangioleiomyomatosis (E-LAM) remaining after lung transplantation (LT) for P-LAM. This report examines the efficacy of SRL treatment for the patient with E-LAM remaining after an LT for P-LAM. CASE SUMMARY: The course of the patient's recovery from an LT for P-LAM was complicated by lymphedema in the left femoral region that was caused by two E-LAM lesions remaining in the left pelvic cavity and in the retroperitoneal area. After the LT was performed, the patient started SRL treatment to reduce the E-LAM lesions. The daily SRL dose, selected based on the standard SRL dose for P-LAM, was initiated at 1 mg/d and was maintained at 2 mg/d. The remaining E-LAM lesions and lymphedema in the left femoral region improved in approximately 9 months after the LT with the administration of both SRL and the standard immunosuppressive therapy used by Okayama University Hospital, including tacrolimus, mycophenolate mofetil, and prednisolone. The SRL and tacrolimus trough concentrations in whole blood were maintained within the therapeutic window for the next 1.5 years after initiation of SRL treatment. The patient experienced no severe adverse events that required discontinuation of the SRL treatment during this time. CONCLUSION: The patients with remaining E-LAM lesions may receive SRL treatment to improve the quality of life after LT for P-LAM as effective therapy in cases where the patient's recovery is complicated by E-LAM lesions.

Microvascular disturbances in the colonic mucosa in antibiotic-associated haemorrhagic colitis: involvement of platelet aggregation.

An ultrastructural study of the colonic mucosa was performed in four patients with antibiotic-associated haemorrhagic colitis and new findings are reported. Colonoscopy was performed and biopsy specimens were obtained within 24 h of the onset of bloody diarrhoea. Colonoscopy demonstrated diffuse oedematous and haemorrhagic mucosa with erosions and white coat. Light microscopy revealed mucosal haemorrhage and inflammatory cell infiltration. Ultrastructurally, platelet aggregation was frequently present in the lumina of colonic mucosal capillaries, causing engorgement of red blood cells in adjacent microvessels. Mild to severe damage was observed in capillary endothelial cells, including discontinuity of basement membranes, gaps between endothelial cells and the destruction of capillaries. There was no evidence of microvascular spasm. In conclusion, our findings suggest that antibiotics directly or indirectly cause microcirculatory disturbances, which result in tissue damage and haemorrhage, in the colonic mucosa.

Radioimmunoassay for erythrocyte acidic GSH S-transferase.

We have developed a RIA for erythrocyte acid glutathione S-transferase (GST), which is immunologically identical to major GSTs from other blood cell components, and measured its serum concentrations in various hematological disorders. In some patients with paroxysmal nocturnal hemoglobinuria, chronic myelomonocytic leukemia, chronic myelocytic leukemia, polycythemia vera and myelofibrosis, the concentrations were high. Very high levels were found in 2 of 3 patients with acute lymphocytic leukemia, while acute myelocytic leukemia exhibited a modest increment. No or little increase was seen in aplastic anemia and myelodysplastic syndrome except chronic myelomonocytic leukemia. It is suggested that the measurement of serum acidic GST may be of use as a clinical marker of increased destruction and/or overproduction of blood cells.

Fructose-6-phosphate,2-kinase activity in human erythrocytes.

The hemolysate partially purified from human red cells was demonstrated to be capable of synthesizing fructose-2,6-bisphosphate (F-2,6-P2) from fructose-6-phosphate in the presence of adenosine triphosphate (ATP) indicating that human red cells contain fructose-6-phosphate,2-kinase. The effect of F-2,6-P2 on the rate-limiting enzymes of glycolysis, ie, hexokinase, phosphofructokinase (PFK), and pyruvate kinase, has also been examined. PFK was activated by this metabolite and the half-maximum activation was obtained at a concentration of 10(-7) mol/L. Neither hexokinase nor pyruvate kinase was affected by F-2,6-P2. These results suggest that human erythrocytes may contain this metabolite as one of the positive effectors for PFK.

Immunological cross-reactivity of human glutathione S-transferases from blood cells.

Antibody against glutathione S-transferase (GST) from human erythrocytes precipitated GST activities from platelets, neutrophils, mononuclear cells and blast cells of acute lymphocytic leukemia, indicating that those GSTs share the immunologically identical determinants. It is possible that they are under the same genetic control.

Phosphoglycolate synthesis by human erythrocyte pyruvate kinase.

R2-type pyruvate kinase purified monogeneously from human red cells catalyzes the phosphorylation of glycolate (glycolate kinase). Maximum activation of glycolate kinase was observed at 100 microM fructose-1,6-bisphosphate (Fru-1,6-P2) and at 2 mM glucose-1,6-bisphosphate (Glc-1,6-P2). The Km for ATP was 1.1 mM in the absence of Fru-1,6-P2 and 1.5 mM in the presence of 1 mM Fru-1,6-P2. The Km for glycolate was 20 mM in the absence of Fru-1,6-P2 and 5 mM in the presence of 1.0 mM Fru-1,6-P2. The optimum pH was over 10.5. At the physiological concentrations of Fru-1,6-P2, Glc-1,6-P2 and ATP, the glycolate kinase activity is too low to maintain the reported level of phosphoglycolate (approx. 2-5 microM). It is demonstrated that phosphorylation of glycolate by R2-type pyruvate kinase which is predominant in mature red cells plays no physiological role. The questions whether an unknown pathway for phosphoglycolate synthesis exists or whether there is actually phosphoglycolate in red cells are raised.

Enzyme activities of cultured erythroblasts.

The enzyme activities of cultured early erythroid progenitor cells (burst-forming unit erythroid, BFU-E) were measured and were compared with the activities of mature erythrocytes. The enzyme activity of acetylcholinesterase was not detectable in the erythroblasts. The ratios of phosphofructokinase and glutathione peroxidase were low due to low enzyme activities in both the erythroblasts and erythrocytes. The ratios of triose phosphate isomerase, phosphoglycerate kinase, and adenylate kinase were low due to high enzyme activities in both the erythroblasts and erythrocytes. The ratios of hexokinase, glucose phosphate isomerase, monophosphoglyceromutase, pyruvate kinase, and adenosine deaminase were high due to high enzyme activities in the erythroblasts. The isozyme of erythroblast hexokinase was of the prototype isozyme I, while pyruvate kinase was predominantly of the prototype M2, with two hybrid isozymes to the anodal side by electrophoresis. These facts suggest that there is a greatly different metabolic pattern during the maturation of the erythroid cells.

[A clinical study on cefoperazone in serious infections associated with hematological malignancy].

Clinical and bacteriological efficiencies of cefoperazone (CPZ) in 19 serious infections associated with hematological malignancy were studied. CPZ was clinically effective in 13 cases (68.4%). Excellent effects were obtained in 3 cases (15.8%), good effects in 7 cases (36.8%) and fairly good effects in 3 cases (15.8%). The rate of clinical effectiveness by CPZ was not dependent on neutrophils number in peripheral blood. Bacteriological effectiveness to isolated organisms in 15 cases was obtained in 9 cases (60%). Clinically significant serum concentrations of CPZ persisted over 6 hours after injection (1 g/l hour, d.i.v.). In comparative study of MIC against clinically isolated P. aeruginosa, CPZ was superior to other cephalosporins. Adverse reactions were not significant except for 3 cases with abnormalities of hepatic function.