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Biomedical subjects

L Bowman

Publications and source records attributed to L Bowman.

At least 19 recordsLinked to original sources
PubMed2001

Biology and outcome of childhood acute megakaryoblastic leukemia: a single institution's experience.

To describe the clinical and biologic features of pediatric acute megakaryoblastic leukemia (AMKL) and to identify prognostic factors, experience at St Jude Children's Research Hospital was reviewed. Of 281 patients with acute myeloid leukemia treated over a 14-year period, 41 (14.6%) had a diagnosis of AMKL. Six patients had Down syndrome and AMKL, 6 had secondary AMKL, and 29 had de novo AMKL. The median age of the 22 boys and 19 girls was 23.9 months (range, 6.7-208.9 months). The rate of remission induction was 60.5%, with a 48% rate of subsequent relapse. Patients with Down syndrome had a significantly higher 2-year event-free survival (EFS) estimate (83%) than did other patients with de novo AMKL (14%) or with secondary AMKL (20%; P < or =.038). Among patients who had de novo AMKL without Down syndrome, 2-year EFS was significantly higher after allogeneic bone marrow transplantation (26%) than after chemotherapy alone (0%; P =.019) and significantly higher when performed during remission (46%) than when performed during persistent disease (0%; P =.019). The 5-year survival estimates were significantly lower for de novo AMKL (10%) than for other forms of de novo AML (42%; P <.001). Treatment outcome is very poor for patients with AMKL in the absence of Down syndrome. Remission induction is the most important prognostic factor. Allogeneic transplantation during remission offers the best chance of cure; in the absence of remission, transplantation offers no advantage over chemotherapy alone. (Blood. 2001;97:3727-3732)

Bone Marrow Transplantation↗
PubMed2001

Feasibility of four consecutive high-dose chemotherapy cycles with stem-cell rescue for patients with newly diagnosed medulloblastoma or supratentorial primitive neuroectodermal tumor after craniospinal radiotherapy: results of a collaborative study.

PURPOSE: This study was designed to determine the feasibility and safety of delivering four consecutive cycles of high-dose cyclophosphamide, cisplatin, and vincristine, each followed by stem-cell rescue, every 4 weeks, after completion of risk-adapted craniospinal irradiation to children with newly diagnosed medulloblastoma or supratentorial primitive neuroectodermal tumor (PNET). PATIENTS AND METHODS: Fifty-three patients, 19 with high-risk disease and 34 with average-risk disease, were enrolled onto this study. After surgical resection, high-risk patients were treated with topotecan in a 6-week phase II window followed by craniospinal radiation therapy and four cycles of high-dose cyclophosphamide (4,000 mg/m2 per cycle), with cisplatin (75 mg/m2 per cycle), and vincristine (two 1.5-mg/m2 doses per cycle). Support with peripheral blood stem cells or bone marrow and with granulocyte colony-stimulating factor was administered after each cycle of high-dose chemotherapy. Treatment of average-risk patients consisted of surgical resection and craniospinal irradiation, followed by the same chemotherapy given to patients with high-risk disease. The expected duration of the chemotherapy was 16 weeks, with a cumulative cyclophosphamide dose of 16,000 mg/m2 and a planned dose-intensity of 1,000 mg/m2/wk. RESULTS: Fifty of the 53 patients commenced high-dose chemotherapy, and 49 patients completed all four cycles. The median length of chemotherapy cycles one through four was 28, 27, 29, and 28 days, respectively. Engraftment occurred at a median of 14 to 15 days after infusion of stem cells or autologous bone marrow. The intended dose-intensity of cyclophosphamide was 1,000 mg/m2/wk; the median delivered dose-intensity was 1,014, 1,023, 974, and 991 mg/m2/wk for cycles 1 through 4, respectively; associated median relative dose-intensity was 101%, 102%, 97%, and 99%. No deaths were attributable to the toxic effects of high-dose chemotherapy. Early outcome analysis indicates a 2-year progression-free survival of 93.6% +/- 4.7% for the average-risk patients. For the high-risk patients, the 2-year progression-free survival is 73.7% +/- 10.5% from the start of therapy and 84.2% +/- 8.6% from the start of radiation therapy. CONCLUSION: Administering four consecutive cycles of high-dose chemotherapy with stem-cell support after surgical resection and craniospinal irradiation is feasible in newly diagnosed patients with medulloblastoma/supratentorial PNET with aggressive supportive care. The early outcome results of this approach are very encouraging.

Adolescent↗
PubMed2001

Successful unrelated donor bone marrow transplantation for paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disease of hematopoiesis due to a mutation in the PIG-A gene. Affected patients may demonstrate hemolysis or venous thrombosis, and may develop MDS or aplastic anemia. Successful results may be obtained after conditioning and transplantation from syngeneic or genotypically matched sibling donors. Experience with transplantation from matched unrelated donors (MUD) is limited to eight patients, with only one survivor. We report three patients who underwent successful MUD BMT for PNH. All three patients had severe aplastic anemia (SAA) and PNH at the time of BMT. Unrelated donors were six-antigen HLA-matched (n = 2) or HLA-A mismatched (n = 1). Conditioning consisted of cytarabine, cyclophosphamide, TBI, and ATG. Grafts were T cell-depleted by anti-CD6/CD8 antibodies + complement. Further GVHD prophylaxis consisted of cyclosporine. Patients received 0.7-1.1 x 10(8) nucleated cells/kg and 1.1-2.1 x 10(6) CD34(+) cells/kg. Neutrophil engraftment occurred at 16-21 days. One patient developed grade 1 acute GVHD. Although all three patients experienced significant transplant-related complications, they ultimately resolved and all patients are alive and well 30-62 months after BMT. T cell-depleted MUD BMT is an effective treatment option for PNH-related MDS and SAA.

Adolescent↗
PubMed2001

HC-Pro suppression of transgene silencing eliminates the small RNAs but not transgene methylation or the mobile signal.

Post-transcriptional gene silencing (PTGS) is a sequence-specific RNA degradation mechanism that is widespread in eukaryotic organisms. It is often associated with methylation of the transcribed region of the silenced gene and with accumulation of small RNAs (21 to 25 nucleotides) homologous to the silenced gene. In plants, PTGS can be triggered locally and then spread throughout the organism via a mobile signal that can cross a graft junction. Previously, we showed that the helper component-proteinase (HC-Pro) of plant potyviruses suppresses PTGS. Here, we report that plants in which PTGS has been suppressed by HC-Pro fail to accumulate the small RNAs associated with silencing. However, the transgene locus of these plants remains methylated. Grafting experiments indicate that HC-Pro prevents the plant from responding to the mobile silencing signal but does not eliminate its ability to produce or send the signal. These results demonstrate that HC-Pro functions downstream of transgene methylation and the mobile signal at a step preceding accumulation of the small RNAs.

Algorithms↗
PubMed2001

A comparison of abciximab use in MCO and non-MCO populations.

OBJECTIVE: To compare abciximab use in managed care organization (MCO) patients and non-MCO patients undergoing coronary angioplasty, specifically (1) the factors influencing abciximab use, (2) the impact of abciximab on hospital length of stay (LOS), and (3) differences in results in MCO and non-MCO patients. STUDY DESIGN: A retrospective observational study based on data from 87 US hospitals on 13,384 angioplasty patients. PATIENTS AND METHODS: Multivariate analysis was used to control for a wide range of factors (patient demographics, health conditions, admission information, and hospital characteristics) that may influence the likelihood of receiving abciximab and hospital length of stay (LOS). Estimation was conducted via a 2-stage sample selection model. RESULTS: Comorbidities, hospital characteristics, and geographic regions influenced abciximab use in MCO and non-MCO populations. In the non-MCO population, women and minority group members were significantly less likely than white male patients to receive abciximab. Both MCO and non-MCO angioplasty patients who were given abciximab had significantly shorter LOSs (0.66 +/- 0.27 fewer days and 0.87 +/- 0.13 fewer days, respectively) than did patients who were not given this drug. CONCLUSIONS: Access to care for MCO and non-MCO populations differed. Non-MCO women and minorities were less likely than non-MCO white men to receive abciximab, but this difference was not observed in the MCO population. After controlling for high-risk indications and selection bias, MCO and non-MCO patients who received abciximab had significantly shorter LOSs than did those who did not receive abciximab. This finding is consistent with the many clinical trials that have observed a reduction in ischemic complications associated with abciximab use.

Abciximab↗
PubMed2000

A calmodulin-related protein that suppresses posttranscriptional gene silencing in plants.

Posttranscriptional gene silencing (PTGS) is an ancient eukaryotic regulatory mechanism in which a particular RNA sequence is targeted and destroyed. The helper component-proteinase (HC-Pro) of plant potyviruses suppresses PTGS in plants. Using a yeast two-hybrid system, we identified a calmodulin-related protein (termed rgs-CaM) that interacts with HC-Pro. Here we report that rgs-CaM, like HC-Pro itself, suppresses gene silencing. Our work is the first report identifying a cellular suppressor of PTGS.

Agrobacterium tumefaciens↗
PubMed2000

The seed coat-specific expression of a subtilisin-like gene, SCS1, from soybean.

A seed coat-specific gene, SCS1 (Seed Coat Subtilisin 1), from soybean, Glycine max [L.] Merill, has been identified and studied. The gene belongs to a small family of genes with sequence similarity to the subtilisins, which are serine proteases. Northern blot analysis showed that SCS1 RNA accumulates to maximal levels in seed coats at 12 days post anthesis, preceding the final stages of seed coat differentiation. The SCS1 RNA was not found in other tissues including embryos, seed pods, flowers, stems, roots or leaves. In-situ hybridization studies confirmed the temporal pattern of expression observed by Northern blot analysis and further revealed a restricted pattern of RNA accumulation in thick-walled parenchyma cells of the seed coats. These cells are important in the apoplastic translocation of nutrients en route to the embryo from the vascular tissues. The tissue-specific subtilisin-like gene may be required for regulating the differentiation of the thick-walled parenchyma cells.

Amino Acid Sequence↗
PubMed2000

Differential costs and outcomes among pediatric oral antibiotic formulations identified from a large prescription database.

Differential performance of oral antibiotics continues to be a difficult characteristic to measure. As payers make efforts to identify selected antibiotics to place on their formularies or to reimburse, the challenge to these decision-makers is to determine which agent will work best in their population. Given the differences from one clinical trial to another, identifying performance characteristics that might impact effectiveness in clinical practice is quite challenging. This study's aim was to determine which beta-lactam and macrolide antibiotic provided the best clinical and economic outcome when used in difficult pediatric infections that previously experienced amoxicillin or cotrimoxazole failure. The findings demonstrated that cefaclor, azithromycin, and amoxicillin/clavulanate were associated with a decreased need for subsequent antibiotic therapy. Total drug treatment costs for beta-lactams and macrolides were lowest for cefaclor and azithromycin, respectively. These results are consistent with previous published literature and seem plausible given potential compliance advantages of these products as reported in studies of product tolerability and taste.

Administration, Oral↗
PubMed2000

Cognitive and academic functioning in survivors of pediatric bone marrow transplantation.

PURPOSE: To evaluate cognitive and academic functioning in survivors of pediatric bone marrow transplants (BMTs) at 1 and 3 years after a BMT. PATIENTS AND METHODS: In a prospective, longitudinal design, patients underwent a comprehensive battery of neurocognitive measures before admission for transplantation and at 1, 3, and 5 years after a BMT. This article describes a cohort of 102 survivors with follow-up data available for 1 year after a BMT, including 54 survivors with follow-up available for 3 years. This represents the largest cohort of pediatric BMT survivors yet reported in a prospective study. RESULTS: In the cohort as a whole, there were no significant changes on global measures of intelligence (intelligence quotient [IQ]) and academic achievement at either 1 or 3 years after a BMT, despite adequate power to detect an IQ change of three points or greater. Likewise, performance on specific tests of neuropsychologic function remained stable. No significant differences were observed between patients whose conditioning regimen included total-body irradiation (TBI) and those whose did not. The primary predictor of neurocognitive outcome was patient age, with younger patients more likely to show declines over time. The subset of patients who were less than 3 years of age at the time of transplantation seemed to be particularly vulnerable to cognitive sequelae. CONCLUSION: The use of BMTs with or without TBI entails minimal risk of late neurocognitive sequelae in patients who are 6 years of age or older at the time of transplantation. However, patients who are less than 6 years of age at the time of transplantation, and particularly those less than 3 years of age, seem to be at some risk of cognitive declines.

Adolescent↗
PubMed2000

Shorter hospital stays for angioplasty patients who receive abciximab.

The purpose of this retrospective study is to examine the effect of abciximab treatment on hospital length of stay for patients undergoing angioplasty in a naturalistic setting. Multivariate analysis was used to control for a wide range of factors (patient demographics, insurance provider, health conditions, admission and discharge information, and hospital characteristics) that may influence length of stay. Estimation was conducted on a sample of 13,384 angioplasty patients via a two-stage sample selection model. In addition, the model was re-estimated for a subgroup of 4,800 patients who underwent angioplasty and were also diagnosed with acute myocardial infarction. The study finds that patients in poorer health were more likely to receive abciximab. After adjusting for high-risk indications and selection bias, results also indicate that angioplasty patients (n = 13,384) who are given abciximab have a significantly shorter length of stay (0.89+/-0.12 fewer days) than those patients who did not receive abciximab. In a subgroup analysis of patients who had an acute myocardial infarction (n = 4,800), patients receiving abciximab were also found to have significantly shorter hospital stays (0.54+/-0.26 fewer days) than patients who did not receive abciximab. These results indicate that there are potential economic benefits for hospitals administering abciximab.

Abciximab↗
PubMed2000

An international feasibility study of parental decision making in pediatric oncology.

PURPOSE/OBJECTIVES: To describe parental decision making about treatment options for children with cancer and determine the feasibility of a similar but larger international study. DESIGN: Exploratory. SETTINGS: A pediatric catastrophic illness research hospital in the United States and children's hospitals in Australia and Hong Kong. SAMPLE: A convenience sample of 43 parents (5 fathers and 38 mothers ages 23-59 years). METHODS: Six open-ended interview questions posed to parents during private individual interviews. Content analysis techniques were used. MAIN RESEARCH VARIABLES: Parental perceptions of (a) factors considered in the decision-making process, (b) behaviors of healthcare professionals that affected the process, and (c) satisfaction with the process. Feasibility of a larger study was estimated by considering ease of access to parents, number of refusals to participate, understanding of the interview questions, and level of interest at each setting. FINDINGS: Access to parents was possible at all sites. Refusal to participate was reported only at the U.S. site. Certain factors (e.g., getting information from the healthcare team, trusting staff) were important to all parents considering end-of-life decisions. Site-specific factors included considering alternative therapies (at the Australian site) and strengthening faith (at the U.S. site). CONCLUSIONS: A larger international study of parental decision making is feasible. Sufficient similarities in parental decision making exist across these sites to justify future efforts to identify universal decision-making factors that, in conjunction with site-specific differences, could be helpful in developing guidelines for healthcare professionals who assist parents in making treatment-related decisions for a sick child.

Adolescent↗
PubMed1999

Comparison of energy estimation equations with measured energy expenditure in obese adolescent patients with cancer.

Obesity is increasing in the US adolescent population. As the number of obese adolescents increases, obesity is becoming a more frequent problem in the hospital setting, sometimes causing patients to have complicated and prolonged hospital stays. Calculation of the energy requirements of obese adolescent patients with chronic diseases such as cancer is complicated by increased energy requirements as a result of disease state and growth. This study examined the accuracy of the commonly used equations for calculating energy requirements. Estimated energy expenditure was compared with measured energy expenditure determined by indirect calorimetry. All energy estimation equations were inaccurate, which indicates the need for a specific equation for determination of energy needs in this special patient population. Until further research is done, indirect calorimetry is recommended for all obese adolescent patients with cancer who require nutrition support.

Adolescent↗
PubMed1999

Pulmonary surfactant inhibits LPS-induced nitric oxide production by alveolar macrophages.

The objectives of this investigation were 1) to report that pulmonary surfactant inhibits lipopolysaccharide (LPS)-induced nitric oxide (. NO) production by rat alveolar macrophages, 2) to study possible mechanisms for this effect, and 3) to determine which surfactant component(s) is responsible. NO produced by the cells in response to LPS is due to an inducible. NO synthase (iNOS). Surfactant inhibits LPS-induced. NO formation in a concentration-dependent manner;. NO production is inhibited by approximately 50 and approximately 75% at surfactant levels of 100 and 200 microg phospholipid/ml, respectively. The inhibition is not due to surfactant interference with the interaction of LPS with the cells or to disruption of the formation of iNOS mRNA. Also, surfactant does not seem to reduce. NO formation by directly affecting iNOS activity or by acting as an antioxidant or radical scavenger. However, in the presence of surfactant, there is an approximately 80% reduction in the amount of LPS-induced iNOS protein in the cells. LPS-induced. NO production is inhibited by Survanta, a surfactant preparation used in replacement therapy, as well as by natural surfactant. NO formation is not affected by the major lipid components of surfactant or by two surfactant-associated proteins, surfactant protein (SP) A or SP-C. However, the hydrophobic SP-B inhibits. NO formation in a concentration-dependent manner;. NO production is inhibited by approximately 50 and approximately 90% at SP-B levels of 1-2 and 10 microgram/ml, respectively. These results show that lung surfactant inhibits LPS-induced. NO production by alveolar macrophages, that the effect is due to a reduction in iNOS protein levels, and that the surfactant component responsible for the reduction is SP-B.

Animals↗
PubMed1998

IL-2 adenovector-transduced autologous tumor cells induce antitumor immune responses in patients with neuroblastoma.

In many different murine models, the immunogenicity of tumor cells can be increased by transduction with a range of immunostimulatory genes, inducing an immune response that causes regression of pre-existing unmodified tumor cells. To investigate the relevance of these animal models to pediatric malignancy, we used autologous unirradiated tumor cells transduced with an adenovirus-IL-2 to immunize 10 children with advanced neuroblastoma. In a dose-escalation study, we found that this tumor immunogen induced a moderate local inflammatory response consisting predominantly of CD4(+) T lymphocytes, and a systemic response, with a rise in circulating CD25(+) and DR+ CD3(+) T cells. Patients also made a specific antitumor response, manifest by an IgG antitumor antibody and increased cytotoxic T-cell killing of autologous tumor cells. Clinically, five patients had tumor responses after the tumor immunogen alone (one complete tumor response, one partial response, and three with stable disease). Four of these five patients were shown to have coexisting antitumor cytotoxic activity, as opposed to only one of the patients with nonresponsive disease. These results show a promising correlation between preclinical observations and clinical outcome in this disease, and support further exploration of the approach for malignant diseases of children.

Adenoviridae↗
PubMed1998

Costs and effects in therapy for acute coronary syndromes: the case of abciximab in high-risk patients undergoing percutaneous transluminal coronary angioplasty in the EPIC study. Evaluation of 7E3 for the Prevention of Ischemic Complications.

Cost-effectiveness analyses are routinely performed to determine whether the additional cost of a novel therapy is balanced by additional effectiveness. The definitions of costs and effects involve a variety of assumptions, both in general economic terms and with regard to the specific medical setting under consideration. Similarly, differing criteria for acceptability of cost-effectiveness estimates can be used to generate different conclusions regarding cost-effectiveness. The issues and problems inherent in economic evaluation are discussed by an analysis of findings with the platelet glycoprotein IIb/IIIa inhibitor abciximab in the EPIC (Evaluation of 7E3 for the Prevention of Ischemic Complications) study in high-risk patients undergoing percutaneous transluminal coronary angioplasty.

Abciximab↗
PubMed1998

Phase I study of DMP 840 in pediatric patients with refractory solid tumors.

The bis-naphthalimide DMP 840 has demonstrated high level antitumor activity in a number of preclinical models and has been evaluated in several Phase I studies in adults. We enrolled 10 patients with refractory pediatric solid tumors to this Phase I study of DMP 840 given intravenously by short infusion daily for 5 days. The most frequent and dose-limiting toxicity was myelosuppression. The maximum tolerated dose on this schedule was 8.6 mg/m2 daily for 5 days. One patient had a complete response; there were no measurable tumor responses among the remaining 9 patients.

Adolescent↗
PubMed1998

Constitutive nitric oxide production by rat alveolar macrophages.

Results from previous studies suggest that alveolar macrophages must be exposed to inflammatory stimuli to produce nitric oxide (.NO). In this study, we report that naive unstimulated rat alveolar macrophages do produce .NO and attempt to characterize this process. Western blot analysis demonstrates that the enzyme responsible is an endothelial nitric oxide synthase (eNOS). No brain or inducible NOS can be detected. The rate of .NO production is approximately 0.07 nmol.10(6) cells-1.h-1, an amount that is less than that produced by the eNOS found in alveolar type II or endothelial cells. Alveolar macrophage .NO formation is increased in the presence of extracellular L-arginine, incubation medium containing magnesium and no calcium, a calcium ionophore (A-23187), or methacholine. .NO production is inhibited by NG-nitro-L-arginine methyl ester (L-NAME) but not by NG-nitro-L-arginine, L-N5-(1-iminomethyl)ornithine hydrochloride, or aminoguanidine. Incubation with ATP, ADP, or histamine also inhibits .NO formation. Some of these properties are similar to and some are different from properties of eNOS in other cell types. Cellular .NO levels do not appear to be related to ATP or lactate content. Alveolar macrophage production of .NO can be increased approximately threefold in the presence of lung surfactant or its major component, dipalmitoyl phosphatidylcholine (DPPC). The DPPC-induced increase in .NO formation is time and concentration dependent, can be completely inhibited by L-NAME, and does not appear to be related to the degradation of DPPC by alveolar macrophages. These results demonstrate that unstimulated alveolar macrophages produce .NO via an eNOS and that lung surfactant increases .NO formation. This latter effect may be important in maintaining an anti-inflammatory state in vivo.

Adenosine Triphosphate↗