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Biomedical subjects

R L Heideman

Publications and source records attributed to R L Heideman.

67 records · Page 4Linked to original sources
PubMed1985

Pediatric phase I trial and pharmacokinetic study of tiazofurin (NSC 286193).

Tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide), a new nucleoside antimetabolite, was evaluated in a phase I trial involving children with refractory cancers. The drug was administered i.v. as a 10-min infusion daily for 5 consecutive days repeated at 3-week intervals. The dose ranged from 550 to 3300 mg/sq m/day. Seventeen patients received 23 courses and were evaluable for toxicity. The maximally tolerated dose was 2200 mg/sq m/day. The major dose-limiting toxicities were nonhematological. Neurotoxicity, including headache, drowsiness, and irritability, was common and was the principal dose-limiting toxicity at the higher doses. Severe myalgias were also dose limiting in one patient. Other side effects were mild, reversible elevations in serum transaminases; nausea, vomiting, and diarrhea; mild hypertension; dysphagia; and exfoliative dermatitis of the hands and feet. Myelotoxicity was not significant. The pharmacokinetics of tiazofurin was studied in 16 patients. Plasma disappearance was triphasic with half-lives of 9.7 min, 1.6 h, and 5.5 h. Clearance was dose related, ranging from 120 ml/min/sq m at 550 mg/sq m/day to 70 ml/min/sq m at 3300 mg/sq m/day. The primary route of elimination was renal with 85% of the drug recoverable in the urine as the parent compound in the 24 h following administration.

Adolescent↗
PubMed1984

Free and total putrescine in cerebrospinal fluid quantified by reversed-phase liquid chromatography.

This is a simple, rapid, sensitive method for routine quantification of the polyamine putrescine (1,4-diaminobutane) in cerebrospinal fluid. Sample preparation involves protein precipitation, acid hydrolysis for 18 h (if total putrescine is to be measured), pre-column derivatization with o-phthalaldehyde, and extraction into acetonitrile. The derivative is separated and quantified by "high-performance" liquid chromatography on a reversed-phase C18 radial-compression column. A single chromatographic run takes less than 18 min. Putrescine concentrations as low as 50 nmol/L in cerebrospinal fluid can be detected.

Chemical Precipitation↗
PubMed1983

Intermittent combination chemotherapy with or without bacillus Calmette-Guérin for treatment of acute lymphoblastic leukemia of childhood.

Seventy-four children ranging in age from 6 months to 17.5 years with acute lymphoblastic leukemia newly diagnosed between 1976 and 1979 were entered on a study incorporating intermittent chemotherapy with or without the addition of bacillus Calmette-Guérin (BCG). The chemotherapy program consisted of induction with vincristine, dexamethasone, and intrathecal methotrexate, intensification with adriamycin and asparaginase, central nervous system treatment with cranial irradiation and intrathecal methotrexate, and continuation treatment with 5-day courses of combination chemotherapy administered every three weeks. The first phase of continuation therapy incorporated vincristine, adriamycin, 6-mercaptopurine, and dexamethasone. In the second phase, oral methotrexate was substituted for the adriamycin in non-T-cell patients; in T-cell patients, cytosine arabinoside or cyclophosphamide and methotrexate in alternating cycles were substituted for the adriamycin and asparaginase was added. Total duration of therapy was approximately 2.5 years. Connaught BCG was administered by Heaf gun on days 8 and 15 of each 3-week cycle for the first 8 months of treatment in approximately one-third of the patients. Actuarial disease-free survival with a median follow-up of 59 months shows no difference in outcome between the BCG and non-BCG poor-risk patients. However, there is an improvement in disease-free survival of BCG-treated good- and average-risk girls (P = 0.04). While patients were actively receiving BCG there was also a trend toward the development of fewer significant infections than when patients were not receiving BCG (P = 0.85). Toxicities from BCG administration included satellite rashes, local tenderness, lymphadenopathy, secondary infection, and residual scars. Overall disease-free survival by actuarial analysis is 60% at 6 years; for patients with unfavorable prognostic features it is 40%. In this trial the addition of BCG prolonged the disease-free survival of girls with good- and average-risk prognostic features and also may have decreased the susceptibility to infection while it was being administered. However, the benefit does not appear sufficient to warrant its routine use, especially in view of the toxicities encountered.

Adolescent↗
PubMed1982

Acute leukemia associated with the t(4;11) chromosome rearrangement: ultrastructural and immunologic characteristics.

The acute leukemia associated with the t(4;11) chromosome rearrangement is characterized by relatively consistent clinical features: occurrence primarily in young individuals, hyperleukocytosis, and poor response to therapy. This study describes the morphological, ultrastructural, and immunologic characteristics of the leukemic cells from ten patients with this type of leukemia. The morphological features of the leukemic blasts vary from lymphoid-appearing to monocytic. Ultrastructurally and cytochemically, some of the lymphoid-appearing blasts possess features of myeloid origin. The immunologic phenotype is characteristically E- SIg- CALLA- BA-1- BA-2+ HLA-DR+ and TdT+. These findings suggest that the t(4;11)-associated acute leukemia represents a proliferation of an early myeloid progenitor cell.

Acute Disease↗
PubMed1978

Lymphocytic leukemia in children: prognostic significance of clinical and laboratory findings at time of diagnosis.

Forty-eight children with untreated acute lymphocytic leukemia were evaluated with regard to their clinical presentation and the surface membrane characteristics, mitogen responsiveness, and cytochemical staining features of their lymphoblasts. The presence at diagnosis of 20% or more bone marrow lymphoblasts possessing T-cell surface markers was associated with the development of early relapse and death. Age, sex, initial peripheral leukocyte count (WBC), lymph node enlargement or the presence of hepato- or splenomegaly bore no statistically significant relationship to the patient's lymphoblast type, and only a WBC in excess of 10(5)/microliter correlated with a poor prognosis. Leukemic T-cells were found to be periodic acid-Schiff negative from nearly all patients, helping to distinguish such patients from the larger group of children whose leukemic cells were PAS positive, but negative for T-cell membrane features. In those patients who had multiple relapses, the surface membrane characteristics, staining features, and mitogen responses of their lymphoblasts remained constant. This suggests that relapse occurs in the same clone of malignant cells present at diagnosis and that the above features may be reliably used to evaluate and classify patients beyond the time of diagnosis.

Adolescent↗
PubMed1976

Acute leukemia in Burkitt lymphoma.

Burkitt lymphoma uncommonly presents as a acute leukemia. We describe the clinical course and findings of a 14-year-old female with Burkitt lymphoma who presented with acute leukemia. splenomegaly and an abdominal mass. She responded initially to prednisone alone and later achieved full remission with combination chemotherapy. Established morphologic criteria and clinical course were consistent with the diagnosis of Burkitt lymphoma (1), although B-cell determinants were not present on her tumor cells.

Abdominal Neoplasms↗
PubMedDate not supplied

Cerebrospinal fluid pharmacokinetics and toxicology of intraventricular and intrathecal arabinosyl-5-azacytosine (fazarabine, NSC 281272) in the nonhuman primate.

Arabinosyl-5-azacytosine (AAC), a new nucleoside antimetabolite, is broadly active in preclinical tumor screening evaluations. To assess the potential for intrathecal use of this drug, we studied the toxicity and pharmacokinetics of intrathecal and intraventricular administration in nonhuman primates. Four adult male rhesus monkeys were given single 10 mg intrathecal (n = 1) or intraventricular (n = 3) doses of AAC to determine its acute toxicity and pharmacokinetic parameters. An additional 3 animals were given four weekly 10 mg intrathecal doses to assess the systemic and neurologic toxicity associated with chronic administration. Disappearance from the cerebrospinal fluid (CSF) was biexponential, and CSF clearance was 0.2 ml/min, which exceeds the rate of CSF bulk flow by 5-fold. The peak CSF concentration and area under the concentration x time curve achieved with the intraventricular administration of 10 mg were one hundred, and fifty fold greater, respectively, than those achieved after an intravenous dose of 200 mg/kg (1500-2400 mg) in prior experiments. No clinically evident neurotoxicity was observed in either the single or the weekly x 4 dose groups. A slight, transient CSF pleocytosis and increased CSF protein was observed. Systemic toxicity was limited to one animal in the weekly x 4 dose group who demonstrated a mild and transient decrease in his peripheral leukocyte count unassociated with a change in his hematocrit or platelet count. These studies in nonhuman primates demonstrate a clear pharmacokinetic advantage for intrathecal vs systemic administration of AAC. This is demonstrated by a 50-fold greater CSF drug exposure with an intrathecal or intraventricular dose 1/200th of that which can be given systemically.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Tamoxifen and carboplatin for children with low-grade gliomas: a pilot study at St. Jude Children's Research Hospital.

PURPOSE: The authors conducted a single-arm, prospective study using tamoxifen and carboplatin for the treatment of children with progressive or symptomatic low-grade gliomas. PATIENTS AND METHODS: Fourteen children with consecutively diagnosed cases of low-grade glioma were enrolled in this Study; all patients were younger than 14 years. One patient was excluded after induction chemotherapy because of the diagnosis of a nonmalignant condition. Patients were treated with daily tamoxifen (20 mg/m2 administered twice per day) in addition to targeted, monthly intravenous carboplatin at an area under the curve (AUC) exposure of 6.5 mg/mL x minute for 1 year or until they had clinical or radiologic evidence of disease progression. RESULTS: The median age at diagnosis was 5.3 years, the median age at initiation of chemotherapy was 8.3 years. Eight patients had tumors of the hypothalamus/optic pathway, two patients had thalamic tumors, and one patient each had tumors in the temporal lobe, tectum, and brain stem. Tumor histologic findings included fibrillary astrocytoma (n = 2), juvenile pilocytic astrocytoma (n = 6), and oligodendroglioma (n = 1). The best response to therapy was a partial response in two patients, stable disease in nine patients, and progressive disease in two patients. The overall survival at 3 years is 69%. The 3-year progression-free survival is 47%. Tamoxifen and carboplatin chemotherapy did not result in a significant number of objective responses in children with low-grade gliomas. The progression-free survival is similar to that of other published series. Nonmyelosuppressive agents such as tamoxifen deserve additional evaluation in the treatment of children with low-grade gliomas.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Response of pediatric low grade gliomas to chemotherapy.

Thirteen patients with low grade astrocytomas were treated with alkylating agent or platinum-based chemotherapy regimens. Eleven of these patients received chemotherapy as their initial postoperative treatment modality, and 2 others as treatment for progressive disease postradiation therapy. Responses were objectively determined using CT or MRI. One patient had a complete response (CR), 6 had partial responses (PR), and 3 others had stable disease (SD) as their best response. Clinical responses paralleled those determined objectively. Chemotherapy was well tolerated with the exception of ototoxicity in 4 patients treated with cisplatin. Despite good initial responses, 5 of 6 patients who received no further treatment postchemotherapy (4 PR, 1 SD) developed progressive disease 5-13 months after completing chemotherapy. The remaining 4 patients with objective responses or stable disease (1 CR, 2 PR, 1 SD), all received further postchemotherapy treatment with radiation therapy or surgery, and have not demonstrated disease progression. Our experience suggests that alkylator or platinum-based chemotherapy can successfully delay the growth of these locally infiltrative neoplasms, and should be considered in their primary management. Despite the experience of others, further therapy appears necessary in patients with residual CT or MRI abnormalities postchemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗