PubMed Health⌕ Search

Biomedical subjects

D G Poplack

Publications and source records attributed to D G Poplack.

At least 217 records · Page 12Linked to original sources
PubMed1978

Acute lymphoblastic leukemia followed by chronic myelocytic leukemia.

Second hematologic malignancies occur rarely in patients previously treated for leukemia. This report describes a patient with acute lymphoblastic leukemia who remained in complete remission for 5 yr and then developed chronic myelocytic leukemia (CML). The original lymphoblasts were associated with a partial deletion of chromosome 21, while CML was associated with a classic Philadelphia marker, indicating the independent origin of the two leukemias.

Acute Disease↗
PubMed1978

Sequential combination chemotherapy (containing high-dose cyclophosphamide) for metastic osteogenic sarcoma.

Eleven patients with metastatic osteogenic sarcoma were treated with cyclophosphamide, adriamycin, and, in some cases, high-dose methotrexate. In the event of metastatic progression, the dose of cyclophosphamide was escalated by increasing the number of consecutive daily infusions (dose, 45 mg/kg/day). The results indicate that metastatic osteogenic sarcoma is marginally responsive to adriamycin and cyclophosphamide but rarely responsive to high-dose methotrexate as administered in this trial. The response of metastatic lesions was not improved by escalating the dose of cyclophosphamide.

Adolescent↗
PubMed1978

"Concentration x time" methotrexate via a subcutaneous reservoir: a less toxic regimen for intraventricular chemotherapy of central nervous system neoplasms.

Neurotoxicity associated with intrathecal methotrexate therapy has been shown to correlate with elevated concentrations of the drug in the cerebrospinal fluid as well as with the total cumulative dosage. In our study 19 patients with meningeal leukemia were randomized to receive courses of intraventricular methotrexate via an Ommaya reservoir consisting of either single injections of 12 mg/sq m/dose or a low-dose "concentration x time" (C x T) schedule of 1 mg every 12 hr for 3 days. There were no significant differences between the two treatment groups in the rate of remission induction, the number of relapses, or the durations of remission. The mean (+/- 1 SD) cumulative methotrexate dose was 66 +/- 41 mg/sq m in the C x T group and 173 +/- 64 mg/sq m in the 12 mg/sq m/dose group (p less than 0.005). Neurologic toxicity occurred in one of the eight patients in the C x T group and in seven of ten patients in the 12 mg/sq m/dose group (p less than 0.05). These observations suggest that the C x T dosage schedule is less neurotoxic and equally effective in the treatment of central nervous system leukemia.

Adolescent↗
PubMed1978

Acceleration of myeloid recovery from cyclophosphamide-induced leukopenia by pretreatment with Bacillus Calmette-Guérin.

Treatment of C57BL/6 mice with Bacillus Calmette-Guérin i.p. 8 days prior to the induction of leukopenia by cyclophosphamide (300 mg/kg i.p.) significantly (p less than 0.002) increased peripheral granulocyte counts on each day during the recovery from leukopenia. The recovery of lymphocyte counts was unaffected by Bacillus Calmette-Guérin treatment. Further experiments indicated that the accelerated granulocyte recovery was the result of an earlier initiation of the recovery process rather than of the release of stored granulocytes. Bacillus Calmette-Guérin may have clinical value as a stimulator of myelopoiesis in patients rendered leukopenic by antineoplastic chemotherapy.

Animals↗
PubMed1977

Primate model for long-term study of intraventricularly or intrathecally administered drugs and intracranial pressure.

Meaningful pharmacokinetic investigations require animal systems which approximate the human situation. This report describes a primate model in which silicone catheters are placed into the fourth ventricle and the spinal subarachnoid space and connected to subcutaneous cerebrospinal fluid without tissue damage, prod, enables spinoventricular perfusion, and permits ventricular cerebrospinal fluid sampling over extended periods in unanethetized rhesus monkeys. This animal system may provide intraventricular pressure recordings and pharmacokinetic data similar to that obtained in man.

Animals↗
PubMed1977

Blindness during remission in two patients with acute lymphoblastic leukemia: a possible complication of multimodality therapy.

Two patients with acute lymphoblastic leukemia treated on the same protocol became blind during complete remission. Therapy consisted of systemic combination chemotherapy, prophylactic central nervous system irradiation and monthly intrathecal cytosine arabinoside. Eight months after CNS irradiation visual acuity in both patients began to decrease. Meningeal leukemia in the area of the chiasm was suspected but despite additional radiotherapy, steroids and continued intrathecal therapy, both patients were blind within 6 months. Numerous lumbar punctures were negative for leukemic cells. Extensive investigation, including craniotomy in one case, failed to reveal the cause of blindness. Biopsy of the optic nerve in one case was compatible with radiation toxicity. We postulate that potentiation of radiation toxicity to the optic nerves and chiasm by systemic chemotherapy, intrathecal chemotherapy, or both, may have led to blindness. The patients continue in complete hemotologic and CNS remission 12 and 29 months after becoming blind.

Acute Disease↗
PubMed1977

Effect of Corynebacterium parvum, methanol-extraction residue of BCG, and levamisole on macrophage random migration, chemotaxis, and pinocytosis.

Three parameters of macrophage function: random migration, chemotaxis, and pinocytosis, were studied in the guinea pig after administration of Corynebacterium parvum, methanol-extraction residue of BCG, and levamisole (LMS), a synthetic anthelmintic. Macrophage migration studies were performed with a modified Boyden chamber. Pinocytosis was assessed by the uptake of colloidal 198Au. After ip administration, each of the three immunostimulators induced an increase in macrophage chemotactic responsiveness and, to a lesser extent and duration, in random motility. Kinetic, dose-response, and time course data for the effect of each agent on macrophage movement were explored. LMS was the most effective stimulator of macrophage activation, which occurred earlier and persisted longer than it did with the other agents. Macrophages from animals receiving each of the agents showed enhanced pinocytosis. Measurement of macrophage random migration, chemotaxis, and pinocytosis appeared to provide a rapid and quantitative assessment of several parameters of macrophage function and, when studied with other immunologic parameters, may provide useful tools for the evaluation of potential immunoadjuvants.

Animals↗
PubMed1977

Computer assisted tomography in methotrexate encephalopathy.

Five children with acute lymphocytic leukemia (ALL) developed encephalopathy following treatment with intrathecal or intraventricular methotrexate (MTX). In these patients computer assisted tomography was informative by revealing areas of decreased attenuation coefficient located periventricularly and in each centrum semiovale (three cases) and calcifications, mostly in the deep and cortical gray matter (two cases), as well as ventricular dilatation (four cases). Contrast injection used in one of these five patients, as well as in another child (not affected by ALL) with MTX encephalopathy, failed to reveal enhancement.

Acute Disease↗
PubMed1977

A primate model for study of methotrexate pharmacokinetics in the central nervous system.

A new technique enabling repetitive sampling of cerebrospinal fluid (CSF) in unanesthetized rhesus monkeys was developed to study the pharmacokinetics of methotrexate (MTX) in the CSF. CSF and plasma MTX levels were monitored following intraventricular and intravenous MTX administration. CSF and plasma MTX disappearance curves in the monkey were virtually identical to curves generated in humans, suggesting that the mechanisms of transport between the CSF and plasma compartments are similar in both species. These observations validate this experimental primate model and indicate its potential application to the pharmacological study of CNS chemotherapeutic agents in man.

Animals↗
PubMed1976

Hepatitis B virus infection in the Wiskott-Aldrich syndrome.

Testing of paired serum samples of 12 children with the Wiskott-Aldrich syndrome for the presence of hepatitis B surface antigen (HBsAg) antibody to HB, Ag, and antibody to the hepatitis B core antigen revealed evidence of hepatitis B virus infection in three. None of the three, however, developed overt clinical hepatitis or the chronic HBsAg carrier state. These data suggest that the immunologic defects seen in the Wiskott-Aldrich syndrome permit adequate immune responses to the hepatitis B virus and do not predispose to the chronic HBsAg carrier state.

Antibodies, Viral↗
PubMed1976

Reversible dementia temporally associated with intraventricular therapy with methotrexate in a child with acute myelogenous leukemia.

During maintenance therapy with intraventricular methotrexate, progressive dementia developed in a child with meningeal leukemia. Cerebrospinal fluid levels of MTX were in the nontoxic range and neurologic evaluation failed to demonstrate anatomic obstruction, infection, or folate depletion. The patient's symptoms gradually resolved when the methotrexate was discontinued, suggesting that methotrexate neurotoxicity may occur in the absence of an elevated CSF concentration of MTX.

Child, Preschool↗
PubMed1976

Monocyte-mediated antibody-dependent cellular cytotoxicity: a clinical test of monocyte function.

The lack of a simple, rapid, and quantitative test of the functional activity of the monocyte has hampered studies of the contribution of this cell type to host defense and human disease. This report describes an assay of antibody-dependent cellular cytotoxicity, which depends exclusively upon the monocyte as the effector cell and therefore provides a convenient test of monocyte function. In this system, mononuclear leukocytes (MNL) obtained by Ficoll-Hypaque separation of whole blood are cytotoxic for 51Cr-labeled human erythrocyte targets coated with anti-blood group antibody. Removal of phagocytic monocytes from the MNL by iron ingestion, followed by exposure to a magnetic field, completely abolishes all cytotoxic activity from the remaining MNL population. Similarly, in severely mono-cytopenic patients with aplastic anemia, cytotoxic effector activity is absent. In normals and less severely monocytopenic aplastic anemia patients, cytotoxicity correlates significantly (p less than 0.001) with monocyte number. Application of this monocyte-mediated antibody-dependent cellular cytotoxicity assay to the study of patients with the Wiskott-Aldrich syndrome has revealed defective monocyte cytotoxic activity in spite of normal monocyte numbers, suggesting that this test may be useful for the assessment of monocyte function in a variety of clinical situations.

Anemia, Aplastic↗
PubMed1976

The effect of Mycobacterium bovis (Bacillus Calmette-Guérin) on macrophage random migration, chemotaxis, and pinocytosis.

Macrophage random migration, chemotactic responsiveness, and pinocytosis were studied in the guinea pig after Bacillus Calmette-Guérin (BCG) administration. Oil-induced peritoneal exudate cells were evaluated for random migration and chemotaxis in modified Boyden chambers. Pinocytosis was measured by the in vitro uptake of colloidal 198Au. There was a parallel increase in random migration and chemotaxis after an i.p. dose of 1.0 X 10(7) COLONY-FORMING UNIts of BCG. This was seen as early as Day 4, sustained through Day 21, and absent by Day 44. A number of different strains and preparations of BCG vaccine exerted a similar augmentation of macrophage mobility. In parallel assays, aliquots of macrophages from BCG-treated animals showed increased pinocytosis, first noted at Day 14, peaking at Day 28, and no longer measurable at Day 44. These alterations in macrophage function following BCG administration may in part contribute to the antitumor effect of BCG adjuvant therapy.

Animals↗
PubMed1975

Candida arthritis treated with amphotericin B.

This report describes a patient with acute lymphoblastic leukemia who developed arthritis of the knee caused by Candida tropicalis. Systemic therapy with amphotericin B apparently suppressed but did not eliminate the infection. Resolution of the arthritis occurred only after three intra-articular injections of amphotericin B. Intra-articular administration of amphotericin B may be a useful adjunct to systemic antifungal therapy in the treatment of these infections.

Amphotericin B↗
PubMed1975

A clinical trial of chemotherapy and RAJI immunotherapy in advanced acute lymphatic leukemia.

Patients in remission with advanced acute lymphatic leukemia were randomly assigned to receive chemotherapy alone or chemotherapy plus immunotherapy with a Burkitt lymphoma tissue culture cell line (RAJI). Remission duration in both groups were identical. Complement-dependent cytotoxic antibody was seen in 5 of 8 immunized patients and 0 of 8 controls. This antibody reacted with RAJI and both allogeneic and autologous acute leukemia cells. Antibody titers began to rise after 2 months, peaked at 4 months, and then declined prior to relapse in all patients. The time course of the increase in mixed-leukocyte culture response to RAJI was similar to immunized patients. An increased in vitro response to phytohemagglutinin was seen during drug administration in all patients. Although no clinical benefit was seen in this small number of patients with the RAJI injections, these in vitro responses are encouraging and new immunization schedules will be investigated.

Antibodies, Neoplasm↗