Search PubMed⌕ Search

Biomedical subjects

D Mahoney

Publications and source records attributed to D Mahoney.

At least 37 records · Page 2Linked to original sources
PubMed1988

Single- vs double-lumen central venous catheters in pediatric oncology patients.

Double-lumen central venous catheters (CVCs) have been introduced recently for use in pediatric patients. The objective of our study was to determine if double-lumen CVC usage increased the possibility of infectious and mechanical complications compared with that of traditional single-lumen CVCs in a population at high risk for infection (oncology patients). Thirty pediatric patients (2.5 +/- 3.0 years old; mean +/- SD) who received single-lumen CVCs were compared with 31 patients (5.9 +/- 4.7 years old) who received double-lumen CVCs. The incidence of infectious complications was compared while controlling for potential confounding variables. Fifty-seven percent (17/30) of patients in the single-lumen group experienced bacteremia or cellulitis that required removal of six catheters compared with a rate of 52% (16/31) and nine catheter removals in the double-lumen group. Fewer manipulations occurred in the single-lumen group compared with the double-lumen group, but the incidence of mechanical complications tended to be greater. When managed carefully, double-lumen CVCs were not associated with a greater risk of infection than single-lumen CVCs.

Bacterial Infections↗
PubMed1988

Clinical trial of etoposide (VP-16) in children with recurrent malignant solid tumors. A phase II study from the Pediatric Oncology Group.

Etoposide (VP-16), 150 mg/M2, given intravenously daily for 3 days every 3 weeks resulted in 3 complete responses and 6 partial responses in 154 patients with a spectrum of recurrent malignant solid tumors. There was evidence of disease control in an additional 37 patients (27 mixed responses and 10 stable disease). These responses occurred primarily in patients with Ewing's sarcoma, Hodgkin's disease, neuroblastoma and rhabdomyosarcoma. Most of the patients had every extensive prior therapy; however prior therapy with teniposide (VM-26), the congener of VP-16, did not seem to preclude responses to the latter drug. Myelosuppression was the principal form of toxicity. Neutropenia characterized by absolute neutrophil counts of 0.5 to 0.9 x 10(9)/L occurred in one-half of the patients, and thrombopenia with platelet counts of less than 25 to 49 x 10(9)/L in one-fourth. These results demonstrate a favorable therapeutic index for VP-16 in several recurrent childhood solid tumors, supporting its use as a component of primary therapy for these diseases.

Adolescent↗
PubMed1988

Intravenous immunoglobulin may lessen all forms of infection in patients receiving allogeneic bone marrow transplantation for acute lymphoblastic leukemia: a pediatric oncology group study.

Fifty patients with refractory acute lymphoblastic leukemia underwent allogeneic bone marrow transplantation after conditioning with high-dose cytosine arabinoside and fractionated total body irradiation. Twenty-nine received intravenous immunoglobulin (i.v.Ig) infusion, primarily to prevent cytomegalovirus infection, and 21 did not. The two groups were biologically comparable. Seven (24.5%) of the i.v.Ig-treated and 14 (66.7%) of the non-i.v.Ig-treated patients developed systemic viral, fungal or bacterial infections and/or interstitial pneumonitis (p less than 0.005), which were fatal in three and 12 cases respectively (p less than 0.001). Currently, 23 (79.3%) of the 29 i.v.Ig-treated and eight (38.1%) of the 21 non-i.v.Ig-treated patients are alive and well (p less than 0.01). We conclude that prophylactic i.v.Ig infusions may reduce the frequency of all forms of serious infection in patients with acute lymphoblastic leukemia undergoing allogeneic marrow transplantation, and thereby improve their survival expectation.

Bone Marrow Transplantation↗
PubMed1987

Functional domains of SIR4, a gene required for position effect regulation in Saccharomyces cerevisiae.

The product of the Saccharomyces cerevisiae SIR4 gene, in conjunction with at least three other gene products, prevents expression of mating-type genes resident at loci at either end of chromosome III, but not of the same genes resident at the MAT locus in the middle of the chromosome. To address the mechanism of this novel position effect regulation, we have conducted a structural and genetic analysis of the SIR4 gene. We have determined the nucleotide sequence of the gene and found that it encodes a lysine-rich, serine-rich protein of 152 kilodaltons. Expression of the carboxy half of the protein complements a chromosomal nonsense mutation of sir4 but not a complete deletion of the gene. These results suggest that SIR4 protein activity resides in two portions of the molecule, but that these domains need not be covalently linked to execute their biological function. We also found that high-level expression of the carboxy domain of the protein yields dominant derepression of the silent loci. This anti-Sir activity can be reversed by increased expression of the SIR3 gene, whose product is normally also required for maintaining repression of the silent loci. These results are consistent with the hypothesis that SIR3 and SIR4 proteins physically associate to form a multicomponent complex required for repression of the silent mating-type loci.

Amino Acid Sequence↗
PubMed1987

A totally implanted venous access system used in pediatric patients with cancer.

A safe and effective method of venous access is important in the care and treatment of patients with malignancies. A recently available totally implantable venous access system offers advantages over traditional central vein catheters (Broviac and Hickman, Houston). We report our experience with the implanted venous access system used in 31 pediatric patients with malignancies. The mean age of the patients was 7 years (range, 6 months to 17 years), and the mean indwelling time of the catheters was 232 days (range, 14 to 607 days; total patient days, 7,198). The catheters were used to administer chemotherapy, drugs, blood products, and parenteral nutrition, as well as to draw blood. Clotting occurred in the catheters on four occasions, requiring removal of two catheters. Fever occurred in eight patients; one developed a local infection at the site of implantation and four developed bacteremia. Our use of the implanted venous access system in children resulted in a lower rate of infection compared with that when the traditional Broviac and Hickman catheters were used, and simplified patient management.

Adolescent↗
PubMed1987

Analysis of surface antigen profile, TdT expression, and T cell receptor gene rearrangement for maturational staging of leukemic T cells: a pediatric oncology group study.

By using monoclonal antibodies specific for T lineage surface antigens, neoplastic T cells from 53 children with T cell acute lymphoblastic leukemia and T cell non-Hodgkin's lymphoma were analyzed and assigned to phenotypically defined stages of T cell maturation. Cells were also analyzed for T cell antigen receptor beta-chain gene and immunoglobulin heavy and light chain gene rearrangements. Clonal rearrangements of T cell antigen receptor beta-chain gene and a germ-line configuration of the immunoglobulin genes were found in cells from all cases. The expression of the terminal deoxynucleotidyl transferase (TdT) in leukemic T cells was studied by both qualitative immunofluorescence and quantitative enzyme immunoassay, and the level of TdT expression was correlated with maturational stages. Lymphoblasts classified as prethymic (3 patients) did not express detectable TdT. In contrast, cells from approximately 60% of the patients with early (15 patients) or intermediate (19 patients) thymocytic phenotypes and approximately 40% of the patients with mature thymocytic phenotype (16 patients) were positive for TdT. Thus, in these leukemic clones TdT was randomly expressed and showed no correlation with maturational stage.

Antibodies, Monoclonal↗
PubMed1983

Influence of dietary polyunsaturated fatty acids on renal & aortic prostaglandin synthesis in 1 kidney 1 clip Goldblatt hypertensive rats.

To study the influence of dietary modification on prostaglandin synthesis and on blood pressure regulation, the effects of dietary enrichment with linolenic or linoleic acid was compared with standard rat chow in 3 groups of 13 rats before and after renal artery constriction and contralateral nephrectomy. Before renal artery constriction 4 weeks supplementation with 40 en% linseed oil (53% linolenic acid) increased renal linolenic acid, decreased arachidonic acid, and suppressed synthesis of 6-keto-PGF1 alpha and PGE2 by renal homogenates (33% and 38% respectively, p less than 0.01) compared with standard diet. Rats fed on 40 en % sunflower seed oil (63% linoleic acid) increased renal prostaglandin synthesis (p less than 0.05) compared with linseed oil, but not compared with standard diet. Seven weeks after renal artery constriction renal and aortic 6-keto-PGF1 alpha and PGE2 were suppressed 30% to 50% (p less than 0.05) by linseed oil supplements compared with sunflower seed oil and standard diets. In the sunflower seed oil group aortic 6-keto-PGF1 alpha correlated (r = 0.75, p less than 0.02) with final systolic blood pressure. Final systolic blood pressures were similar in linseed oil (152.9 mm Hg +/- se 3.3, sunflower oil (155.1 +/- se 6.6) and standard diet group (159.0 +/- se 4.2). Thus dietary linseed oil suppressed renal and aortic prostaglandin synthesis but did not accentuate renal hypertension, and linoleic acid supplementation did not protect against 1 kidney 1 clip renal hypertension.

Animals↗
PubMed1983

Intraarterial cis-platinum chemotherapy for patients with primary and metastatic brain tumors.

A total of 49 patients were treated using intraarterial cis-platinum infusions at a dose of 100 mg/m2. The patients were separated into three groups. There were 13 patients with metastatic tumors, 10 with recurrent malignant gliomas, and 22 patients with high-grade gliomas who received intraarterial cis-platinum as part of an adjuvant program. In addition, four nongliomatous primary brain tumors were treated in this fashion. Cis-platinum was filtered immediately prior to intraarterial infusion using a 0.22-micron filter. Response to treatment was evaluated by follow-up CAT scans and neurologic examinations. There were three complete and eight partial responses in metastatic tumors, and eight partial responses in recurrent gliomas. The median survival was 19 weeks for patients with metastatic disease, and 16 weeks for patients with recurrent gliomas. Those high-grade glioma patients who received intraarterial cis-platinum as adjuvant chemotherapy along with CCNU and radiation therapy had a projected median survival of 91+ weeks. Toxicity from intraarterial cis-platinum following drug filtration was markedly reduced when compared with previous reports. Only five patients experiencing visual or central nervous system toxicity utilizing filtered cis-platinum and no radiographic or histopathologic evidence of central nervous system toxicity was observed. Bilateral deafness was observed following vertebral artery infusion in both patients treated in this manner and thus vertebral artery infusions should be avoided. Systemic toxicity was mild. Intracarotid infusion is a safe, well-tolerated delivery system for filtered cis-platinum with a high response rate for patients with both metastatic and primary malignant brain tumors.

Brain↗
PubMed1983

Basal and pentagastrin stimulated 6-keto prostaglandin F1 alpha secretion in dog stomach.

The effect of pentagastrin on gastric secretion of prostacyclin (PGI2) was studied by measuring the output of 6-keto-prostaglandin F1 alpha in the gastric juice of 8 dogs before and after an intramuscular injection of pentagastrin. A similar study was done in 7 control dogs not given pentagastrin. Pentagastrin was found to significantly increase the gastric secretory output of acid and 6-keto PGF1 alpha during the first 30 minutes after the pentagastrin injection. This was highly significant when compared to the control group. It is concluded that pentagastrin stimulates gastric prostacyclin secretion.

6-Ketoprostaglandin F1 alpha↗
PubMed1981

Dissociation of beta-adrenergic stimulation of renin secretion and prostacyclin synthesis in the rabbit kidney.

The effect of inhibition of prostaglandin (PG) synthesis with indomethacin on basal and isoproterenol-stimulated renin secretion was examined in the isolated perfused rabbit kidney. 6-keto PGF1 alpha' the stable metabolite of prostacyclin, was measured in urine by radioimmunoassay using 125I labelled histamine coupled to 6-keto PGF1 alpha as ligand. The level in urine, prior to isolation and perfusion of the kidney, was 10.7 +/- 5.6 ng/min, and this was reduced to 0.32 +/- 0.25 ng/min (P less than 0.05) in rabbits treated with 2.0 mg/kg of indomethacin. Renin release was markedly stimulated by intrarenal infusion of isoproterenol (0.1 microgram/min) but urinary 6-keto PGF1 alpha did not change. These responses were not affected by indomethacin treatment. Renal perfusion pressure, perfusate flow rate and consequently renal vascular resistance, remained relatively constant during the course of perfusion and were unaltered by indomethacin treatment. These results therefore do not support a role for PGs, and in particular prostacyclin, in the renin response to beta-adrenergic stimulation with isoproterenol.

6-Ketoprostaglandin F1 alpha↗
PubMed1981

Do membrane lipids modify the ouabain-sensitivity of cardiac (Na,K)ATPase?

We investigated whether membrane lipids can alter the affinity of cardiac (Na,K)ATPase (ATP phosphohydrolase, EC 3.6.1.6) for ouabain. We recombined partially (80-95%) delipidated membrane proteins from a digitalis-sensitive species (dog) with membrane lipids from a relatively digitalis-insensitive species (rat) or vice versa, and estimated the affinity of (Na,K)ATPase for ouabain in these hybrid membranes by measuring the half-maximal inhibitory concentration (I50). Delipidation reduced the enzyme activity by 90-95%, but 40-60% of the original activity could be restored with lipids from the same or from the other species and distribution of [14C]phosphatidylcholine showed complete mixing between the native and foreign lipids. In these hybrid cardiac membranes affinity (I50) for ouabain was determined by the origin of the (Na,K)ATPase protein and was not modified by the change in membrane lipids.

Animals↗
PubMedDate not supplied

Intensive alternating drug pairs after remission induction for treatment of infants with acute lymphoblastic leukemia: A Pediatric Oncology Group Pilot Study.

PURPOSE: Infants with acute lymphoblastic leukemia (ALL) often enter remission; however, they have a high rate of relapse. To prevent relapse, infants' tolerance of and benefits from early intensive rotating drug pairs as part of therapy were studied. METHODS: After prednisone, vincristine, asparaginase, and daunorubicin induction, 12 intensive treatments (ABACABACABAC) were administered in 30 weeks: A, intermediate dose methotrexate (MTX) and intermediate dose mercaptopurine (MP); B, cytosine arabinoside (Ara-C) and daunorubicin (DNR); C, Ara-C and teniposide (VM-26). Triple intrathecal chemotherapy (Ara-C, MTX, and hydrocortisone) was administered for central nervous system prophylaxis. Continuation therapy consisted of weekly MTX and daily MP for a total of 130 weeks of continuous complete remission. RESULTS: Thirty-three infants (1 year old or younger) with newly diagnosed ALL were treated. Two infants did not respond to induction, 1 died from sepsis during continuation, 1 received a bone marrow transplant, and 24 relapsed. Median time to relapse was 39 weeks. The event-free survival rate at 5 years was 17% (standard error +/- 7.7%). The most significant toxicities occurred during intensification and included fever-neutropenia and bacterial sepsis. CONCLUSION: Although early intensive rotating therapy is tolerable, the relapse-free survival rate remains poor for infants treated with the schedule on this protocol.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Effect of captopril on blood pressure and bradykinin vasodepressor responses after nephrectomy and suppression of prostaglandin synthesis in anaesthetized rats.

1. Captopril markedly potentiated the vasodepressor responses to bradykinin. Neither the magnitude nor duration of the blood pressure fall were altered by bilateral nephrectomy or treatment with indomethacin which suppressed urinary excretion of the prostacyclin metabolite 6-Keto- PGF1 alpha. 2. It is concluded that in the anaesthetized rat augmentation of the bradykinin depressor responses by captopril occurs independently of endogenous prostaglandin synthesis.

Anesthesia, General↗
PubMedDate not supplied

Potentiation of bradykinin by captopril during suppression of prostacyclin synthesis.

The effect of captopril on blood pressure and on the depressor responses to intravenously administered bradykinin was examined in anesthetized normotensive rats during inhibition of prostaglandin synthesis. The hypotensive action of captopril persisted after treatment with indomethacin in doses that markedly suppressed urinary excretion of the prostacyclin metabolite 6-keto prostaglandin F1 alpha. Captopril markedly potentiated the vasodepressor responses to intravenous bradykinin given by bolus injection or continuous infusion. Neither the magnitude nor the duration of the blood pressure fall were affected by treatment with indomethacin. It is concluded that in the anesthetized rat the hypotensive action of captopril and its augmentation of the depressor response to bradykinin is independent of prostacyclin synthesis.

6-Ketoprostaglandin F1 alpha↗