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Biomedical subjects

M H Duncan

Publications and source records attributed to M H Duncan.

At least 19 recordsLinked to original sources
PubMed1997

Visual and verbal short-term memory deficits in childhood leukemia survivors after intrathecal chemotherapy.

Assessed survivors of childhood lymphoblastic leukemia (ALL) treated with intrathecal chemotherapy, using the Wide Range Assessment of Memory and Learning (WRAML), compared to controls without cancer, matched as closely as possible in age, SES, and gender. Mild, but consistent, deficits were found in both visual-spatial and verbal single-trial memory tasks. In multitrial learning, only visual-spatial tasks resulted in deficient scores, while verbal learning was within the normal range. IQ results indicated scores 10-20 points lower in the ALL group. Memory results are related to deficits in strategic planning and attentional distractiveness. The WRAML may be a useful clinical tool to evaluate differential memory deficits in children with ALL.

Adolescent↗
PubMed1997

Economic impact with home delivery of chemotherapy to pediatric oncology patients.

OBJECTIVE: To examine the economic impact of a home chemotherapy program (HCP) for pediatric oncology patients. RATIONALE: Factors that led to initiation of an HCP included availability of specially trained nurses and programmable ambulatory infusion devices at local home care agencies, routine central venous catheter placement, inpatient bed space shortages, and the availability of ondansetron. SETTING: Chemotherapy delivery in the home setting from June 1991 through June 1994. DESIGN: Charge data and nausea and vomiting severity data were collected for patients treated through the HCP. METHODS: Economic impact was calculated by incorporating and summing all charge categories associated with hospital admission for chemotherapy (HAC) versus delivery by the HCP. All data were adjusted for 1993 dollars, and reflect changes for the average patient size (1 m2). Charge data for each chemotherapy protocol delivered in the home were analyzed by calculating the differences between HAC and HCP charges using the following formula: charge difference (HAC - HCP) per protocol times the number of courses. Total economic impact was calculated by summing the differences in charges for each protocol. RESULTS: A total of 262 chemotherapy courses were given to 44 patients (mean age 9.5 +/- 5.1 y) through the HCP, which represented 1012 patient care days and 24 different chemotherapy protocols. Monetary savings from the HCP ranged from $5180 per course of ifosfamide plus etoposide to $367 per course for high-dose methotrexate. Total monetary savings from the HCP during the 3-year period was $640,793. Successful control of nausea and vomiting with a combination of ondansetron plus methylprednisolone was achieved in approximately 80% of the patients receiving highly emetogenic chemotherapy protocols. CONCLUSIONS: HCP for pediatric oncology patients results in substantial monetary savings to payors. Effective control of nausea and vomiting can be accomplished at home in the majority of patients with an ondansetron-based antiemetic regimen.

Adolescent↗
PubMed1996

Multidrug resistance-1 (MDR1) expression and functional dye/drug efflux is highly correlated with the t(8;21) chromosomal translocation in pediatric acute myeloid leukemia.

Resistance to chemotherapy is a major problem in acute myeloid leukemia (AML). An important resistance mechanism in adult AML is active drug efflux mediated by the multidrug resistance protein-1 (MDR1). To determine if MDR1 is important in childhood AML, we examined MDR1 expression and functional dye/drug efflux in 20 pediatric/adolescent AML patients; results were correlated with cytogenetics and clinical outcome. Using flow cytometry, MDR1 protein expression on the leukemic blasts was measured with the antibody MRK16, while efflux was measured by extrusion of the fluorescent dye DiO(C2)3 in the presence/absence of cyclosporin A (CsA). Six of 20 cases expressed MDR1. While all six MDR1+ cases were efflux+, three of 14 MDR1- cases also demonstrated efflux. Both MDR1 and efflux were strongly correlated with the t(8;21). All six MDR1 +/efflux+ cases and 2/3 MDR1 -/efflux+ cases had a t(8;21), while no MDR1-/efflux- cases had a t(8;21) (P < 0.0005). This correlation between MDR1, efflux, and the t(8;21) in pediatric AML was not found in 11 adult t(8;21) cases similarly studied. Although the clinical relevance of MDR1 in pediatric AML awaits larger studies, our results suggest a biologic subset of pediatric AML patients may benefit from regimens which include MDR1-reversing agents or non-MDR1 substrates.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Health care outcomes case study: Febrile neutropenia.

A case study of the clinical and economic impact of filgrastim in cancer patients in the home care setting is described. The risk of febrile neutropenia is greatly reduced when filgrastim therapy is begun prophylactically after a course of antineoplastic drug therapy. Such use of filgrastim may also reduce the need for hospitalization, prevent mucositis, and enable the next course of chemotherapy to be administered on schedule. Investigators at the University of New Mexico, noting studies showing merit in early hospital discharge of pediatric cancer patients with febrile neutropenia, decided to take the approach a step further by treatment febrile neutropenia entirely at home. Patients seen in the pediatric oncology clinic at the university hospital were considered candidates for home treatment if they had stable vital signs, were already receiving filgrastim after the completion of cancer chemotherapy, and lived within one hour of the hospital. Six cancer patients 2-17 years of age were studied between August 1992 and February 1994. These patients had 16 episodes of febrile neutropenia that were treated at home. The drug regimen consisted of prophylactic filgrastim (begun the day after completion of a course of antineoplastic therapy) and ceftazidime (when febrile neutropenia developed). None of the children were readmitted to the hospital. Infections resolved within 12 days in all cases. The total charge for treating the 16 episodes at home was $22,400 (drug charge for ceftazidime, visits by nurses, infusion-pump rental, and ancillary charges). The total charge for hospital treatment of these episodes would be $112,924 (bed charge and pharmacy charge). The difference suggests a potential savings of $90,524 from home care for this small group of patients. Treating febrile neutropenia in pediatric cancer patients at home is effective and cost-efficient if the patients are clinically stable and prophylactic filgrastim therapy has been started after the completion of cancer chemotherapy.

Adolescent↗
PubMed1995

EWS and WT-1 gene fusion in desmoplastic small round cell tumor of the abdomen.

Chromosome translocations found in neoplasms often result in the creation of hybrid genes encoding chimeric proteins. This case study describes a patient with desmoplastic small round cell tumor (DSRCT) of the abdomen, an aggressive neoplasm characterized by translocation of chromosomes 11 and 22. Southern hybridization showed that the Ewing sarcoma gene (EWS) gene was rearranged in the DSRCT. Reverse transcriptase-polymerase chain reaction analysis of tumor cell RNA revealed that exons 1 to 7 of the EWS gene were joined to exons 8 to 10 of the Wilms' Tumor-1 (WT-1) gene resulting in the production of a chimeric message. The WT-1 and EWS genes encode DNA and RNA binding proteins involved in Wilms' tumor and Ewing sarcoma pathogenesis, respectively. The fusion of these two genes in DSRCT results in the production of a putatively oncogenic protein composed of the zinc finger DNA binding domains of WT-1 linked to potential transcriptional regulatory domains of EWS. DNA sequencing revealed the genomic breakpoints of translocation on chromosomes 11 and 22. The genomic breakpoint on chromosome 22 occurred in EWS intron 7 just 2 nucleotides 3' of exon 7. Polymerase chain reaction-based assays were developed that could detect the fused genes in the DSRCT tumor using either RNA or genomic DNA. The potential diagnostic use of these assays is discussed.

Abdominal Neoplasms↗
PubMed1995

Assessment of chemotherapy-induced emesis and evaluation of a reduced-dose intravenous ondansetron regimen in pediatric outpatients with leukemia.

OBJECTIVE: To measure the severity of nausea and vomiting in pediatric patients receiving intravenous or intrathecal chemotherapy for acute lymphoblastic leukemia and to evaluate the effectiveness of 2 intravenous doses of ondansetron for this condition. DESIGN: Patients were surveyed during repeated treatments of maintenance chemotherapy, given with or without ondansetron, using a repeated measures pretest/posttest design. SETTING: Outpatient pediatric oncology clinic. PATIENT POPULATION: Sixteen pediatric patients (aged 2-15 years, mean 6.2) with acute lymphoblastic leukemia. METHODS: Surveys to assess nausea and vomiting and the extent of interference with daily activities were administered following emetogenic chemotherapy with or without ondansetron. RESULTS: A total of 255 surveys following emetogenic chemotherapy with daunorubicin, cyclophosphamide, carmustine, and etoposide and cytarabine combined, as well as intrathecal therapy with methotrexate, hydrocortisone, and cytarabine, were analyzed. Analysis was performed on surveys of 149 courses without antiemetic therapy and 106 courses after 2 doses of ondansetron 0.15 mg/kg iv. The most emetogenic chemotherapy treatment was the etoposide/cytarabine combination (p < 0.05). Ondansetron completely protected patients (defined as no nausea or no vomiting) during most (> 50%) of the chemotherapy treatments, except for those in which cyclophosphamide was used. Ondansetron provided greater control of nausea and vomiting, a higher percentage of complete protection, and decreased the daily activity interference rating for carmustine and etoposide/cytarabine compared with courses of chemotherapy without antiemetics (p < 0.05). Two intravenous doses of ondansetron also provided durable antiemetic efficacy over time for the most emetogenic chemotherapy treatment (etoposide/cytarabine). CONCLUSIONS: Etoposide/cytarabine proved to be the most emetogenic of the chemotherapy treatments studied. A reduced-dose regimen of intravenous ondansetron was shown to be an effective antiemetic for the outpatient treatments with etoposide/cytarabine and carmustine, but not with cyclophosphamide.

Adolescent↗
PubMed1995

Continuous midazolam infusion for the management of morphine-induced myoclonus.

OBJECTIVE: To describe a patient with morphine-induced myoclonus treated with a continuous infusion of midazolam and continued morphine dose escalation. DESIGN: Single case report. SETTING: Delivery, monitoring, and titration of morphine and midazolam in the patient's home by a homecare agency. RESULTS: The use of high dosages of morphine (i.e., 500 mg/h) produced myoclonic spasms in this patient, which in turn resulted in increasing pain. To allow for continuation of effective analgesia and to control the myoclonic spasms, an infusion of midazolam was initiated and titrated. The midazolam infusion allowed for continuation of the morphine dosage and also permitted further dosage escalation. As morphine dosages were further escalated, it was also necessary to increase the midazolam infusion to control additional myoclonic spasms. CONCLUSIONS: Use of a concomitant midazolam infusion with high doses of morphine appears to be safe and is an effective means of controlling morphine-induced myoclonus. If further dosage increase of morphine are necessary in this setting, increases in the midazolam infusion also may be required.

Adolescent↗
PubMed1994

Langerhans'-cell histiocytosis (histiocytosis X)--a clonal proliferative disease.

BACKGROUND: The lesions of Langerhans'-cell histiocytosis (histiocytosis X), a proliferative histiocytic disorder of unknown cause, contain histiocytes similar in phenotype to dendritic Langerhans' cells. The disease ranges in severity from a fatal leukemia-like disorder to an isolated lytic lesion of bone. Intermediate forms of the disease are usually characterized by multiorgan involvement, diabetes insipidus, and a chronic course. METHODS: To determine whether Langerhans' histiocytosis is a polyclonal reactive disease or a clonal disorder, we used X-linked polymorphic DNA probes (HUMARA, PGK, M27 beta[DXS255], and HPRT) to assess clonality in lesional tissues and control leukocytes from 10 female patients with various forms of the disease. Lymphoid clonality was also assessed by analysis of rearrangements at immunoglobulin and T-cell-receptor gene loci. RESULTS: The HUMARA assay detected clonal cells in the lesions of 9 of the 10 patients: 3 patients had acute disseminated disease, 3 had unifocal disease, and 3 had intermediate forms. The percentage of clonal cells closely approximated the percentage of CD1a-positive histiocytes in each lesion. Clonality was also confirmed in two of nine cases with the PGK or M27 beta probe. Extreme constitutional lyonization precluded assessment of clonality in the 10th case. Lymphoid clonality was ruled out in all cases. CONCLUSIONS: The detection of clonal histiocytes in all forms of Langerhans'-cell histiocytosis indicates that this disease is probably a clonal neoplastic disorder with highly variable biologic behavior. Thus, genetic mutations that promote clonal expansion of Langerhans' cells or their precursors may now be identified.

Adolescent↗
PubMed1993

DNA content measurement can be obtained using archival material for DNA flow cytometry. A comparison with cytogenetic analysis in 56 pediatric solid tumors.

BACKGROUND: Although flow cytometry (FCM) has become a widely used technique for the measurement of DNA content in solid tumors, the correlation of ploidy analysis by FCM with cytogenetic analysis (CGA) is not well described. The sensitivities of G-banded CGA and FCM were compared to determine the accuracy of the DNA index value (DI) as a measurement of chromosome number. METHODS: Tumor specimens from 56 pediatric cases were analyzed for DNA content by both FCM and CGA. Nuclei for FCM were prepared from archival tissue in 53 specimens using a modification of the Hedley technique and from fresh tissue in 3 specimens. Metaphase chromosomes for CGA were prepared from standard solid tumor harvests and Giemsa-trypsin banding procedures. Ploidy status for this study was defined as (1) diploid--DI between 0.97 and 1.03 by FCM or chromosome number +/- 2 from normal by CGA (44-48); and (2) aneuploid--DI < 0.97 or > 1.03 by FCM or total chromosomes < 44 or > 48 by CGA. RESULTS: Forty-nine of the 56 pediatric specimens were evaluable by both techniques. Concordance was observed in 34 cases (69%) between the two techniques in assigning similar ploidy status to a tumor (22 diploid and 12 aneuploid). It also was observed that among the aneuploid concordant cases, the actual DI obtained from archival material could predict total chromosome number with 95% accuracy. The 15 discordant cases showed a distinct aneuploid population by FCM, but were diploid by CGA. CONCLUSIONS: A correlation of 69% was obtained between both techniques to assign a similar ploidy status (diploid versus aneuploid) in 56 pediatric solid tumors. These results support the combined use of CGA and FCM to obtain the most complete analysis of DNA content and chromosome abnormalities in pediatric solid tumors. FCM on formalin-fixed, paraffin-embedded tissue can be used to measure total DNA content.

Adolescent↗
PubMed1993

Practical approach to the investigation of neutropenia.

This article discusses the evaluation of a patient for possible neutropenia. An evaluation must include an integration of complex factors such as age- and race-related normal ranges for absolute neutrophil count, an assessment of other hematopoietic elements in blood, an investigation for possible underlying infections, an examination for splenomegaly, and an evaluation for evidence of recurrent infections or family history suggestive of a constitutional neutropenic disorder.

Adult↗
PubMed1992

Age-linked prognostic categorization based on a new histologic grading system of neuroblastomas. A clinicopathologic study of 211 cases from the Pediatric Oncology Group.

Histologic sections (minimum of four sections per patient) from 211 patients with neuroblastoma were reviewed. The tumors were resected before therapy, which was standardized according to age and stage. Low mitotic rate (MR) (less than or equal to ten per ten high-power fields) and calcification emerged as the most significant prognostic features after statistical analysis by stepwise log-rank tests (P less than 0.0001 and P = 0.0065, respectively). Histologic Grades 1, 2, and 3 were defined on the basis of the presence of both, any one, or none of these two prognostic features, respectively (Grade 3 had absence of low MR, i.e., these tumors had high MR [greater than ten per ten high-power fields]). Statistically significant differences in survival were observed in the grades after adjusting for age and stage (P less than 0.001). The degree of differentiation, although significant by itself, was no longer significant after adjusting for the grades. Age groups (less than or equal to 1 versus greater than 1 year of age), which also emerged as an independent prognostic feature (P less than 0.001), were linked with the grades to define two risk groups as follows: (1) a low-risk (LR) group consisting of patients in both age groups with Grade 1 tumors and patients 1 year of age or younger with Grade 2 tumors and (2) a high-risk (HR) group consisting of patients older than 1 year of age with Grade 2 tumors and patients in both age groups with Grade 3 tumors. The difference in survival between LR (160 cases) and HR groups (51 cases) was statistically significant (P less than 0.001). Concordance between these LR and HR groups and the Shimada classification was observed in 84% of cases. The new histologic grading system has the following advantages: (1) use of familiar terminology and histologic features in the grading system and (2) relative ease of assessment because the degree of differentiation does not need to be determined. The grading system should be tested on a new data set with an appropriate histologic sample of similar size to confirm these results.

Age Factors↗