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Biomedical subjects

S Todo

Publications and source records attributed to S Todo.

At least 523 records · Page 29Linked to original sources

Malignant histiocytosis in childhood: clinical, cytochemical, and immunohistochemical studies of seven cases.

Tissue specimens obtained at autopsy from seven childhood cases of malignant histiocytosis were studied by immunohistochemistry. Clinically, the majority of the cases showed sustained fever, hepatosplenomegaly, pancytopenia, and DIC. The pretreatment diagnosis was based on their typical clinical manifestations and bone marrow smear findings. Although three patients temporarily responded to exchange transfusion and chemotherapy, all seven patients eventually died of active disease. Postmortem examination revealed the proliferation of atypical histiocytes appearing in variable degrees of maturation in the lymph nodes, liver, spleen, bone marrow, lungs, and central nervous system. Immunohistochemical staining for lysozyme, nonspecific cross-reacting antigen (NCA), alpha 1-antitrypsin (alpha 1 AT), alpha and beta subunits of S100 protein (S100 alpha, beta), and concanavalin A receptors (ConAR) in cytoplasm demonstrated the presence of two subtypes of malignant histiocytes, ie, S100 beta+/NCA-/ConAR+ (4 cases) and S100 beta-/NCA+/ConA R+ (three cases). The results of lysozyme, alpha 1 AT, and S100 alpha staining were inconsistent. A survey of the literature disclosed that the incidence of S100 protein-positive cases in children was higher than in adults (12/21 v 5/19; chi 2, P less than .05). Further large scale investigation is necessary to confirm the independence and significance of these two subtypes of histiocytes in malignant histiocytosis.

Acid Phosphatase↗

Experience with Orthoclone OKT3 monoclonal antibody in liver transplantation.

Experience with the use of Orthoclone OKT3 monoclonal antibody for the treatment of acute cellular rejection in a series of 130 human orthotopic liver transplantations is reviewed. Treatment was highly effective in reversing rejection, in reducing the rate of retransplantation, and in lowering patient mortality. OKT3 was also useful for cyclosporine sparing in patients with poor renal function, hypertension, or CNS toxicity. There was a significant incidence of opportunistic infection associated with the use of OKT3.

Adrenal Cortex Hormones↗

Orthotopic liver transplantation for primary sclerosing cholangitis.

The incidence or diagnostic rate of sclerosing cholangitis is increasing. Because of the lack of effective medical or surgical therapy for patients with end-stage liver disease and sclerosing cholangitis, results with orthotopic liver transplantation were examined. The results of 55 consecutive liver replacements for this disease were reviewed. The 1- and 2-year actuarial survival rates are 71% and 57%, respectively. Orthotopic liver transplantation for end-stage liver disease from sclerosing cholangitis has emerged as the most effective therapy.

Adenoma, Bile Duct↗

Serum ferritin in stage IV neuroblastoma.

Serum ferritin is known to be one of the tumor markers for neuroblastoma. Serum ferritin is elevated in most children with neuroblastoma who are in stages III or IV, but it is not elevated in those in stage I or II. It has also been observed that iron load caused by blood transfusion shows a greater effect on serum ferritin levels than tumor activity due to neuroblastoma. Thus, serum ferritin increases in a linear fashion in children given repeated blood transfusions but the levels increase exponentially in children who have bulky neuroblastomas. Thus, serum ferritin values must be interpreted with caution in patients with advanced stages of neuroblastoma who inevitably require blood transfusions. The authors propose that the pretransfusion and posttransfusion serum ferritin values be in comparison with other tumor markers such as urinary VMA, urinary HVA, and neuron specific enolase. The serum ferritin level should not be used as a sole indicator of tumor activity in neuroblastoma.

Blood Transfusion↗

Abnormal serum phenylalanine-tyrosine ratio and hyperferritinemia in malignant histiocytosis.

Nine cases of childhood malignant histiocytosis (MH) showed an abnormally high serum phenylalanine (Phe)/tyrosine (Tyr) ratio (3.47 +/- 1.32) coincident with hyperferritinemia (50,800 +/- 33,600 ng/ml). Lactate dehydrogenase activity was also increased in these patients. These values were compared with data on sera from two groups of patients, acute leukemia cases (n = 14) and measles cases (n = 13), and with control values from normal healthy children (n = 38). The Phe/Tyr ratio was 1.57 +/- 0.54 for the acute leukemia (p less than 0.01) and 2.58 +/- 1.46 for the measles cases (NS), serum ferritin was 245 +/- 124 ng/ml for acute leukemia (p less than 0.01) and 167 +/- 117 ng/ml for measles (p less than 0.01). Accordingly, the concurrence of both abnormalities is considered to be characteristic for MH. It was also found that both serum Phe/Tyr ratio and ferritin levels reflect the disease activity, indicating that these two factors are useful prognostic indicators in the treatment of patients with MH.

Adolescent↗

Effect of FK506 in experimental organ transplantation.

FK506 is the most potent immunosuppressive agent known. Its toxicity is substantial in dogs, minor in rats, and unknown in subhuman primates. In small doses that are nontoxic even in dogs, it can be used in synergistic combination with cyclosporine, steroids, and presumably in other drugs.

Animals↗

Immunosuppression of canine, monkey, and baboon allografts by FK 506: with special reference to synergism with other drugs and to tolerance induction.

In dogs the most effective oral dose of FK 506 for prevention of renal homograft rejection was 1.5 mg/kg/day. With maximum credit allowed at 90 days, survival was increased to 61.0 +/- 33.6 (SD) days compared with 13.0 +/- 4.1 in untreated control animals. Higher doses were toxic. The smallest dose that was used (0.5 mg/kg/day) prolonged survival after renal transplantation to 33.7 +/- 23.9 (SD) days. When the small dose of FK 506 was combined with 5 mg/kg/day of cyclosporine and 5 mg of prednisone, five of six canine kidney recipients lived for 90 days. These results were degraded by omission of any of the constituent drugs or reduction by half of the triple drug doses. Thirteen of the dogs treated with various drug regimens lived for 90 days, after which time treatment was stopped; 10 of the dogs eventually rejected the grafts, but three had continued graft function for 6 months or longer and may be permanently tolerant. Moreover, in dogs when 1 mg/kg of intramuscular FK was given to 19 kidney and seven liver recipients for 3 days on postoperative days 1 to 3, 4 to 6, or 7 to 9, the animals survived subsequently for 11 to more than 160 days. All but four of the grafts were eventually rejected, but the prolonged effect of a short course of delayed therapy suggests the possibility of tolerance induction. In cynomolgus monkeys and baboons, FK as a single drug was found to be immunosuppressive after kidney transplantation. Correlation in the dogs and primates between immunosuppression, toxicity, and FK blood levels was not possible because of presently imperfect standardization of assay and monitoring techniques. FK had serious side effects in dogs, but not so obviously in monkeys and not at all in baboons.

Animals↗

Antibody-mediated rejection of human orthotopic liver allografts. A study of liver transplantation across ABO blood group barriers.

A clinicopathologic analysis of liver transplantation across major ABO blood group barriers was carried out 1) to determine if antibody-mediated (humoral) rejection was a cause of graft failure and if humoral rejection can be identified, 2) to propose criteria for establishing the diagnosis, and 3) to describe the clinical and pathological features of humoral rejection. A total of 51 (24 primary) ABO-incompatible (ABO-I) liver grafts were transplanted into 49 recipients. There was a 46% graft failure rate during the first 30 days for primary ABO-I grafts compared with an 11% graft failure rate for primary ABO compatible (ABO-C), crossmatch negative, age, sex and priority-matched control patients (P less than 0.02). A similarly high early graft failure rate (60%) was seen for nonprimary ABO-I grafts during the first 30 days. Clinically, the patients experienced a relentless rise in serum transaminases, hepatic failure, and coagulopathy during the first weeks after transplant. Pathologic examination of ABO-I grafts that failed early demonstrated widespread areas of geographic hemorrhagic necrosis with diffuse intraorgan coagulation. Prominent arterial deposition of antibody and complement components was demonstrated by immunoflourescent staining. Elution studies confirmed the presence of tissue-bound, donor-specific isoagglutinins within the grafts. No such deposition was seen in control cases. These studies confirm that antibody mediated rejection of the liver occurs and allows for the development of criteria for establishing the diagnosis.

ABO Blood-Group System↗

Liver transplantation in the treatment of bleeding esophageal varices.

From March 1980 to July 1987, 1000 patients with various end-stage liver diseases received orthotopic liver transplants. Of the 1000 patients, three hundred two had definite histories of bleeding from esophageal varices before transplantation. There were 287 patients with nonalcoholic liver diseases and 15 patients with alcoholic cirrhosis. All patients had very poor liver function, which was the main indication for liver transplantation. One- through 5-year actuarial survival rates of the 302 patients were 79%, 74%, 71%, 71%, and 71%, respectively. These survival rates are far better than those obtained with other available modes of treatment for bleeding varices when liver disease is advanced. Long-term sclerotherapy is the treatment of primary choice for bleeding varices. Patients in whom sclerotherapy fails should be considered for liver transplantation unless clear contraindications exist.

Esophageal and Gastric Varices↗