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Biomedical subjects

W Krivit

Publications and source records attributed to W Krivit.

267 records · Page 15Linked to original sources
PubMedDate not supplied

Acute parkinsonian syndrome with demyelinating leukoencephalopathy in bone marrow transplant recipients.

A syndrome of rigidity, bradykinesia, spasticity, and often myoclonus and dementia developed acutely in 5 patients who had undergone successful engraftment of bone marrow transplants for the treatment of various hematologic diseases. Magnetic resonance imaging demonstrated widespread changes in white matter; brain biopsy disclosed mild demyelination associated with active phagocytosis of myelin. One patient, who was not treated, remains severely demented. Patients treated with very high-dose methylprednisolone had complete clinical recovery.

Adolescent↗
PubMedDate not supplied

A comparison of methods for detecting leukocyte antibodies in autoimmune neutropenia.

A six-month-old girl and an 18-month-old boy with autoimmune neutropenia due to anti-NA1 are described. The antibodies were detected by granulocyte microagglutination, and their disappearance in the girl coincided with a return of a normal neutrophil count. The autoantibodies in both patients also reacted in the granulocyte cytotoxicity (GC) assay, and in one patient, in the staphylococcal protein A (SPA) assay. However, neither the GC nor the SPA assays showed the anti-NA1 specificity found by agglutination, and the presence of GC and SPA antibodies did not coincide with neutropenia. These three leukocyte antibody techniques may detect different antibodies and have different clinical significances. This report provides additional evidence of the existence of autoimmune neutropenia and indicates that the clinical role of neutrophil antibodies detected by different serologic techniques is not yet established. Antibodies detected by granulocyte agglutination were clinically significant in these two patients with autoimmune neutropenia, while the results of testing with GC and SPA were not.

Absorption↗
PubMedDate not supplied

Genu valgum deformity in Hurler syndrome after hematopoietic stem cell transplantation: correction by surgical intervention.

Hematopoietic stem cell transplantation has increased the survival of patients with Hurler syndrome. Genu valgum occurs frequently in untransplanted patients and has been noted in 52% of our patients after stable engraftment. No deformities spontaneously corrected. We describe the orthopaedic management of genu valgum in Hurler syndrome. Medial epiphyseal stapling predictably affects angular deformity in these patients. Recurrence of deformities either after staple dislodgement or surgical removal can occur, and repeated stapling may be required. Surgical epiphyseal stapling has a role in the management of genu valgum in successfully engrafted Hurler patients. We discuss the relationship of this skeletal deformity to other skeletal deformities and alternative therapies for genu valgum.

Adolescent↗
PubMedDate not supplied

Microglia: the effector cell for reconstitution of the central nervous system following bone marrow transplantation for lysosomal and peroxisomal storage diseases.

Treatment and potential cure of lysosomal and peroxisomal diseases, heretofore considered fatal, has become a reality during the past decade. Bone marrow transplantation, (BMT), has provided a method for replacement of the disease-causing enzyme deficiency. Cells derived from the donor marrow continue to provide enzyme indefinitely. Several scores of patients with diseases as diverse as metachromatic leukodystrophy, adrenoleukodystrophy, globoid cell leukodystrophy, Hurler syndrome (MPS I-H), Maroteaux-Lamy (MPS VI) Gaucher disease, and fucosidosis have been successfully treated following long-term engraftment. Central nervous system (CNS) manifestations are also prevented or ameliorated in animal models of these diseases following engraftment from normal donors. The microglial cell system has been considered to be the most likely vehicle for enzyme activity following bone marrow engraftment. Microglia in the mature animal or human are derived from the newly engrafted bone marrow. Graft-v-host disease activation of the microglia is also of importance. This article will summarize some of the pertinent literature relative to the role of microglia in such transplant processes.

Animals↗
PubMedDate not supplied

Phase II study of VP-16-213 in childhood malignant disease: a Children's Cancer Study Group Report.

VP-16-213, a semisynthetic podophyliotoxin, was tested for antitumor and clinical toxicity in 126 children. The drug was administered iv daily x 5 days every 2 weeks at a starting dose of 75 mg/m2/day. The dose was increased by 25 mg/m2/day/course until clinical response or significant toxicity occurred. The only major toxicity was hematologic, with neutropenia as the most predominant feature. There was one local allergic reaction at the site of injection. No systemic allergic responses were reported. The drug demonstrated significant activity in acute myelomonocytic leukemia with four responses among 19 patients, less activity in acute myelocytic leukemia with two responses among 44 patients, and little activity in acute lymphocytic leukemia with only one partial response among 12 patients. Objective partial responses occurred in ten of 48 patients with solid tumors: two each with Wilms' tumor, lymphoma, and histiocytosis X, and one each with rhabdomyosarcoma, neuroblastoma, Ewing's sarcoma, and undifferentiated carcinoma. The inclusion of VP-16-213 in combination chemotherapy for childhood acute myelomonocytic leukemia and acute myelocytic leukemia appears indicated in patients relapsing after initial therapy. For solid tumors this is an interim report, with further patient accrual required before specific comments can be made.

Bone Marrow↗
PubMedDate not supplied

Phase II trail cisplatin in refractory childhood cancer: Children's Cancer Study Group Report.

A total of 114 children with solid tumors refractory to conventional therapy were evaluated for response and/or toxic effects after receiving cisplatin at doses of 3.0-4.5 mg/kg with aggressive hydration and mannitol diuresis every 3 weeks; a minimum of two courses was required for evaluation of response (110 patients). Objective responses were noted in 18 patients: rhabdomyosarcoma (three), Wilm's tumor (three), osteogenic sarcoma (three). Ewing's sarcoma (two), neuroblastoma (one), undifferentiated sarcoma (one), hepatoblastoma (one), ovarian teratoma (one), hepatocellular carcinoma (one), embryonal carcinoma of the mediastinum (one), and thymoma (one). Twenty-six patients had some evidence of renal toxicity. Asymptomatic hearing loss was commonly found when audiometry was performed (eight of 18 patients tested). Eight additional patients had symptomatic hearing problems--tinnitus or hearing loss. Myelosuppression was mild. Hypomagnesemia and/or hypocalcemia were common but only one patient had symptoms. Cisplatin, administered at a dose of 3.0 mg/kg with aggressive hydration and mannitol diuresis, is reasonably well-tolerated. Its role in the therapy for those tumors against which it shows activity remains to be determined.

Adolescent↗
PubMedDate not supplied

Comparison of the therapeutic response of patients with childhood acute lymphoblastic leukemia in relapse to vindesine versus vincristine in combination with prednisone and L-asparaginase: a phase III trial.

One hundred and seventy-nine previously treated children with acute lymphoblastic leukemia in relapse considered not "resistant" to vincristine (VCR) were randomly allocated to receive reinduction therapy with either vindesine (VND) or VCR, in combination with prednisone and L-asparaginase. Complete remission rates were 57% for both regimens and were significantly greater for first relapsers (69%) than for subsequent relapsers (43%). No significant difference in response rates by regimen was observed within relapse groups. Patients treated with VND experienced significantly greater hematologic toxicity. These data suggest that there is no advantage to using VND instead of VCR in standard reinduction therapy for childhood acute lymphoblastic leukemia in relapse.

Asparaginase↗
PubMedDate not supplied

Phase II evaluation of diglycoaldehyde (Inox) in children with acute leukemia: a children's cancer study group report.

A phase I trial of diglycoaldehyde (Inox) in children with leukemia established that the maximum tolerated dose of a 5-day schedule was 1.5 g/m2/day. A phase II study was undertaken by the Children's Cancer Study Group to evaluate the efficacy of this dose. Forty-seven children with acute leukemia refractory to conventional forms of therapy were entered in the study: 29 patients with acute lymphocyte leukemia/acute undifferentiated leukemia and 18 with acute nonlymphocytic leukemia. Inox was administered at a dose of 1.5 g/m2 as a 4-6 hour iv infusion daily for 5 days every 14 days. Toxic effects included myelosuppression, proteinuria, nausea, vomiting, diarrhea, local tissue reactions, hypocalcemia, transitory serum amylase elevation, and transitory hypotension. There was one life-threatening episode of drug-related renal toxicity. Of the 27 patients who received a minimum of two courses, partial remissions were observed in two patients with acute nonlymphocytic leukemia. Inox was inactive against advanced acute lymphocytic leukemia.

Acute Disease↗
PubMedDate not supplied

PLasma half-life and urinary excretion of cyclophosphamide in children.

The plasma half-life and urinary excretion of cyclophosphamide were determined in 13 children who had various malignancies and/or who were being prepared for bone marrow transplantation. Disappearance from the plasma following iv infusion over a 1-2 hour period was first-order. Urinary excretion was maximal during the first 8 hours after administration and was essentially complete in 24 hours. The plasma half-life in children not receiving known inducers of hepatic microsomal mixed-function oxygenase activity or cyclophosphamide in the 3-week period prior to each determination ranged from 145 to 390 minutes. These values are lower than those ordinarily found in adult patients. The fraction of the total dose excreted in the urine as the parent compound ranged from 4% to 27%. Repeated administration of cyclophosphamide at approximately 30-60 day intervals did not appear to alter its plasma half-life but did appear to increase its urinary excretion. Daily administration of cyclophosphamide (approximately 50 mg/kg/day x 2 or 4) significantly decreased its plasma half-life and urinary excretion suggesting that it may reversibly induce its own metabolism.

Adolescent↗
PubMedDate not supplied

Proton MR spectroscopy of childhood adrenoleukodystrophy.

PURPOSE: To determine the potential of proton MR spectroscopy to monitor patients with childhood-onset cerebral adrenoleukodystrophy (COCALD). METHODS: Single-voxel MR spectroscopy was performed in 16 children with COCALD (24 examinations) who had had no treatment and in 7 children (13 examinations) who had had bone marrow transplantation. RESULTS: In the untreated children with clinically active COCALD, the metabolite ratios N-acetyl-aspartate (NAA)/creatine (Cr) and NAA/choline (Ch) were decreased while Ch/Cr was increased. This trend agrees well with those reported by other researchers, although different experimental sequences and parameters were used in our study. Comparison of these ratios with those from a control group yielded significant differences in the occipital region. In the children who were clinically stable after bone marrow transplantation, the mean levels of the three ratios were between those of the control subjects and the patients with untreated COCALD: the differences in these ratios approached significance. In patients who had been monitored periodically, MR spectroscopy metabolite ratios correlated well with the dementia rating score, reflecting clinical status. CONCLUSION: There is good correlation between MR spectroscopy metabolite ratios and a patient's clinical status. MR spectroscopy appears to be a useful, noninvasive tool to monitor patients with adrenoleukodystrophy, and it increases the overall sensitivity of MR techniques in clinical applications.

Adolescent↗
PubMedDate not supplied

Proton MR spectroscopy and neuropsychological testing in adrenoleukodystrophy.

PURPOSE: To determine early signs of disease in patients with childhood-onset cerebral adrenoleukodystrophy (COCALD) with the use of proton MR spectroscopy. METHODS: Eleven children with posterior COCALD involvement and three children with anterior COCALD involvement were studied with single-voxel proton MR spectroscopy and neuropsychological testing. Findings were compared with those in five healthy control subjects. RESULTS: Areas of abnormal T2 signal intensity in children with COCALD showed abnormal metabolite ratios relative to those of control subjects as follows: decreased N-acetylaspartate (NAA)/Creatine (Cr) and NAA/Choline (Ch) and increased Ch/Cr. Metabolite ratios from normal-appearing brain regions in the same patients also were abnormal, with reduced NAA/Cr and NAA/Ch and increased Ch/Cr values. The mean metabolite ratios in normal-appearing regions were between those in the abnormal regions and those found in the control subjects. Statistical comparison of these ratios with neuropsychological test scores, which are specific for anterior and posterior brain functions, showed a significant correlation with the abnormal metabolite ratios. Our results indicate that the normal-appearing brain regions in these patients are metabolically abnormal. CONCLUSION: Proton MR spectroscopy could be a useful noninvasive tool to evaluate extent of disease in patients with COCALD.

Adolescent↗