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Biomedical subjects

R Chilcote

Publications and source records attributed to R Chilcote.

14 recordsLinked to original sources

Mediastinal germ cell tumor in a child with precocious puberty and Klinefelter syndrome.

An 8-year-old boy presented with precocious puberty and a mediastinal mass. A computer search showed that this rare presentation is most common with germ cell tumor of the mediastinum in children with Klinefelter syndrome. The tumor was completely resected after preoperative chemotherapy, and the patient is well 2 years after the operation. In patients with Klinefelter syndrome, germ cell tumors are 50 times more common than in patients without Klinefelter syndrome, usually contain nonseminomatous elements, present at an earlier age, and are seldom testicular in location.

Child↗

Sickle cell anemia patients have low erythropoietin levels for their degree of anemia.

We have studied serum immunoreactive erythropoietin (SIE) levels in 28 patients with sickle cell anemia (SCA) without renal insufficiency and in 17 patients with nonhemoglobinopathy anemias of comparable severity using a sensitive radioimmunoassay procedure. An exponential relationship between SIE level and degree of anemia was noted in all patients. However, in nonhemoglobinopathy anemia, a sharp rise in the SIE level occurred as hemoglobin (Hb) levels fell below about 12 g/dL, whereas in sickle cell patients the increase was not marked until hemoglobin fell to about 9 g/dL. The response was more blunted in older SCA patients than in younger ones. A linear regression model relating SIE level to Hb level, presence/absence of SCA, and age explained 63% of the variation in SIE. We conclude that the serum erythropoietin levels in SCA increased at a lower hemoglobin concentration and are of a lower magnitude than that of the other anemias.

Adolescent↗

Human triosephosphate isomerase cDNA and protein structure. Studies of triosephosphate isomerase deficiency in man.

Nine cDNA clones of human adult liver triosephosphate (TP) isomerase have been isolated and characterized. All nine appear to be derived from a single mRNA species. DNA sequencing of one clone, designated pHTPI-5a, defined the last two nucleotides of the methionine initiation codon, the entire 744-nucleotide coding region of the mature polypeptide, and the entire 448-nucleotide 3' untranslated region. The frequency of TP isomerase clones in the cDNA library suggests that TP isomerase mRNA is present in adult liver at approximately 25 copies/cell. A single, low abundance TP isomerase mRNA species was detected in RNA isolated from normal human fibroblast cell lines. Analysis of TP isomerase mRNA levels in cultured fibroblasts of individuals that are homozygous for TP isomerase deficiency revealed normal levels in one and approximately 40% of normal levels in another. From this small patient sampling, it can be concluded that the genetic basis for TP isomerase deficiency is heterogeneous.

Amino Acid Sequence↗

Developmental pattern of splenic dysfunction in sickle cell disorders.

Splenic function in sickle hemoglobinopathy syndromes was assessed to determine the developmental pattern of splenic dysfunction. Nonvisualization of the spleen using technetium-99 metastable (99mTc) spleen scans correlated strongly with pocked (vesiculated) RBCs greater than or equal to 3.5%. Cross-sectional analysis of pocked RBC data from 2,086 patients showed differences in the developmental pattern of splenic dysfunction between several disorders. In hemoglobin SS disease (sickle cell anemia) and hemoglobin S beta(0) thalassemia, splenic dysfunction (greater than or equal to 3.5% pocked RBCs) often occurred in the first 6 to 12 months of life. In hemoglobin S beta(+) thalassemia, splenic dysfunction occurred less frequently and later. Splenic dysfunction in hemoglobin SC disease (sickle cell-hemoglobin C) was intermediate. The level of pocked RBCs was inversely associated with fetal hemoglobin (P less than .007) and directly associated with age (P less than or equal to .001). These patterns of splenic dysfunction reflect the known severity of hemolysis and intravascular sickling and are consistent with the epidemiology of severe bacterial meningitis and sepsis in these diseases. Serial measurement of pocked RBCs permits determination of the onset of splenic dysfunction and the time of increased susceptibility to severe bacterial infections.

Age Factors↗

Comparison of vincristine utilized simultaneously or 24 hours before cyclophosphamide in maintenance regimen of acute lymphoblastic leukemia of children: a report of Childrens Cancer Study Group.

A controlled clinical study in children with lymphoblastic leukemia was conducted to measure the potential benefit of time sequencing vincristine and cyclophosphamide. Vincristine and cyclophosphamide were utilized in a maintenance regimen in children after a remission had been obtained. Patients received vincristine either 24 hours before cyclophosphamide or simultaneously with cyclophosphamide. The median time to relapse and the number of continued remissions was significantly increased for patients receiving vincristine 24 hours before cyclophosphamide when compared to those patients receiving both drugs simultaneously. The results of this comparative study indicate that the sequential use of vincristine and cyclophosphamide for maintenance of a second relapse in childhood ALL produces a greater duration of remission than when both are used simultaneously.

Adolescent↗

A new therapy schedule for pediatric non-Hodgkin lymphoma toxicity with preliminary results.

A pilot study of the toxicity and efficacy of a new treatment schedule for childhood non-Hodgkin's lymphoma was conducted by members of the Children's Cancer Study Group (CCSG) prior to its use in a randomized phase III trial. Chemotherapeutic agents used were cyclophosphamide (CPM), vincristine (VCR), and prednisone, together with intravenous (IV) and intrathecal methotrexate (IT MTS). Radiation therapy was also employed. From September 1976 to April 1977, 27 eligible, newly diagnosed patients with non-Hodgkin's lymphoma were entered onto this pilot study. Toxicity was acceptable with minor adjustments in dosage and timing of the myelosuppressive agents. Fourteen of the 22 patients entered onto maintenance remain entirely disease-free, and all have completed the prescribed course of chemotherapy. None of the 12 patients characterized as having a "favorable" prognosis has relapsed, with a median follow-up of 27 months from on study.

Adolescent↗

A study of the cross-resistance of vincristine and vindesine in reinduction therapy for acute lymphocytic leukemia in relapse. A report for Children's Cancer Study Group.

The vinca alkaloid modification product, vindesine, presents closely related molecular structure to vincristine. Although there are differences in capacity to bind tubulin dimer and inability to inhibit growth of several experimental tumors, there is a significant degree of overlap. In the clinical tests to date, vindesine has been used in treatment of children with relapse of acute lymphocytic leukemia considered to be resistant to vincristine. The study presented here was designed to assess the degree of overlap between vincristine and vindesine. The conclusion was reached that there is clinical cross-resistance.

Child↗

An initial report of a phase-III trial comparing vindesine and vincristine for acute lymphocytic leukemia of childhood.

The initial results from the Children's Cancer Study Group (CCSG) study on vindesine are the subject of this report. Vindesine was shown to be active in the treatment of acute lymphocytic leukemia (ALL) in children in a phase-II clinical trial conducted by the CCSG. A phase-II trial is now in progress. The aim of this is to compare the use of vincristine and of vindesine with reference to induction rate, toxicity, and cross-resistance.

Adolescent↗

Transient erythrocytosis during the neonatal period: possible neurologic compications.

Transient erythrocytosis during the neonatal period may result in serious complications. Among the well recognized problems are respiratory distress, acute heart failure, and death. Little attention has been ascribed to the neurologic complications of a high hematocrit level in the neonatal period. This report describes four pediatric patients with neurologic deficits presumably due to transiently high hematocrit levels during the neonatal period. The neurologic findings in these patients were consistent with the general diagnosis of cerebral palsy. We hypothesize that they may be representative of a group of patients with seizures, structural central nervous system defects, and/or mental retardation secondary to transient erythrocytosis. Moreover, prompt recognition and treatment of this hematologic finding may prevent the immediate or late appearance of such neurologic findings.

Cerebral Palsy↗

Hexachlorophene storage in a burn patient associated with encephalopathy.

Hexachlorophene (HCP), a chlorinated phenolic hydrocarbon with bacteriostatic properties against Staphylococcus, is used in a number of topical products. Absorption through normal and damaged human skin has been appreciated and neurologic changes have been described in experimental animals, but instances of human toxicity have been reported infrequently. A 10-year-old boy who sustained a 25% burn did well initially but died in the second week of convalescence with hyperthermia, lower-extremity weakness, and cerebral edema. His treatment had included frequent applications of HCP. Analysis of post-mortem tissue revealed the presence of toxic levels of HCP in the blood (2.2 mug/gm) and brain (2.2 mug/gm), with storage in skin (25 mug/gm), liver (4.4 mug/gm), and fat (6.0 mug/gm). This case suggests that topical applications of HCP in man may result in an extensive absorption with fat storage and may cause fatal encephalopathy.

Brain Diseases↗

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↗