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Biomedical subjects

R Walters

Publications and source records attributed to R Walters.

At least 37 records · Page 2Linked to original sources

Immunohistochemical evaluation of oral myxoid lesions.

Oral examples of neurothekeomas (nerve sheath myxomas), soft tissue myxomas, and focal mucinous and odontogenic myxomas were examined for selected markers. With the use of avidin-biotin complex staining procedures, these specimens of lesions were stained with antibodies to S-100 protein, neurospecific enolase, neurofilaments, desmin, and vimentin. Our results show that the use of immunohistochemical markers for these neural antigens can aid in distinguishing nerve sheath myxomas from other oral myxoid lesions.

Biomarkers, Tumor↗

Determination of bencyclane in human plasma by means of capillary gas chromatography and nitrogen-phosphorus selective detection.

A sensitive and specific method for the determination of bencyclane in human plasma is presented. Bencyclane was extracted from human plasma with two 3-ml volumes of isooctane and was shaken for 10 min. The organic phase was separated and evaporated to dryness at 40 degrees C under a nitrogen stream. The residue was dissolved and an aliquot was injected into the gas chromatograph. The separation was performed with a DB-17 column with helium as the carrier gas. Nitrogen-selective detection was performed. The quantification was performed with the signal output. The limit of detection was 1 ng/ml.

Bencyclane↗

The importance of cytogenetic studies in adult acute lymphocytic leukemia.

PURPOSE: The prognostic importance of pretreatment bone marrow cytogenetic studies in adults with acute lymphocytic leukemia treated at a single institution, with an identical treatment program, is described. PATIENTS AND METHODS: A total of 105 patients with a documented morphologic diagnosis of acute lymphocytic leukemia were reviewed for the purpose of this analysis. All patients had an extensive workup at presentation, and cytogenetic analysis was performed in 103 patients, using the Giemsa banding technique with trypsin pretreatment on 24-hour cultured cells. RESULTS: The specific cytogenetic classification in the 103 patients who had the karyotypic analysis was as follows: diploid 27%; Philadelphia chromosome-positive 13%; hyperdiploid 12%; B-cell karyotype 6%; 6q- and 14q+ abnormalities 4%; pseudodiploid 8%; hypodiploid 2%; and insufficient metaphases 28%. B-cell, 6q- or 14q+, and Philadelphia chromosome-positive karyotypes tended to correlate with other known negative prognostic factors. Patients with diploid, hyperdiploid, pseudodiploid, and hypodiploid karyotypes or with insufficient metaphases could be combined into one group with a favorable prognosis. In this group, the remission rate with induction chemotherapy was 89%, the median complete remission duration was 26 months, and the median survival was 25 months, with a 3-year survival rate of 45%. Patients with Philadelphia chromosome-positive, B-cell, and 6q- or 14q+ abnormalities collectively had an unfavorable prognosis. Their response rate to induction chemotherapy was 65%, the median response duration was 7 months, and the median survival was 8 months, with a 3-year survival rate of less than 10%. CONCLUSION: We conclude that the pretreatment bone marrow karyotype is an important part of the evaluation of adults with acute lymphocytic leukemia and provides significant prognostic information.

Adolescent↗

Response to salvage therapy and survival after relapse in acute myelogenous leukemia.

The response to and survival following first salvage therapy regimens for 243 patients with acute myelogenous leukemia (AML) treated between 1974 and 1985 were evaluated. Eighty (33%) patients obtained a complete remission (CR), 24% died prior to achieving a response, and 43% were resistant on their first salvage regimen. The median survival was 18 weeks. Five percent overall and 16% of the CR patients are predicted to survive for more than 5 years. The factor most strongly associated with response and survival was the duration of the initial remission with 49 of 82 (60%) patients whose initial CR duration was at least 1 year in duration obtaining a second CR v 31 of 161 (19%) for patients with a shorter remission (P less than .01). Age, liver function, serum lactic dehydrogenase (LDH), karyotype, and the proportion of blasts plus promyelocytes present at the time of starting salvage therapy were strongly associated with probability of response and survival. Multivariate analysis was used to develop logistic regression and proportional hazard models to predict probability of response and survival, respectively. The major regimens used were conventional-dose cytarabine (ara-C) (combined with anthracyclines or amsacrine), high-dose ara-C, rubidazone, amsacrine (AMSA), other anthracyclines, and autologous or allogeneic transplant programs. After allowing for the prognostic factors in the models, specific treatment regimens were not strongly associated with prognosis.

Adult↗

Rebound peripheral blastosis with subsequent remission during remission induction in a patient with acute promyelocytic leukemia.

A patient with acute promyelocytic leukemia manifested peripheral blastosis with 50% peripheral blasts and an absolute blast count of 10,000/microliter 2 weeks after the start of induction chemotherapy. The subsequent disappearance of the peripheral and marrow blasts without further chemotherapy was noticed, and complete remission was achieved on day 25 of chemotherapy. The histologic and clinical implications of this phenomenon are discussed.

Adult↗

Mitoxantrone-induced DNA damage in leukemia cells is enhanced by treatment with high-dose arabinosylcytosine.

In a phase II study, patients with chronic myelogenous leukemia in blast crisis (CML-BC) were treated with intravenous (IV) mitoxantrone (5 mg/m2 per day given over 30 min x 5 days and high-dose arabinosylcytosine (ara-C) (3 g/m2 IV q 12 h x 6). The effect of this treatment on DNA damage was studied in the leukemia cells of four patients using the alkaline elution technique modified to measure DNA in unlabeled human cells. A fluorescence assay using Hoechst 33258 dye was applied for the determination of eluted DNA. After a single infusion of mitoxantrone, neither frank nor protein-associated single-strand breaks (SSB) were observed. Even repeated treatment with mitoxantrone on 3 consecutive days did not induce significant SSB. However, after the combined sequential infusion of ara-C and mitoxantrone the DNA elution pattern changed, showing significant DNA damage. SSB remained apparent after 24 h and increased with subsequent doses of ara-C and mitoxantrone. Studies of other patients treated with ara-C alone did not reveal significant SSB (n = 5). Following mitoxantrone infusion the median peak concentrations of intracellular ara-CTP (the triphosphate of ara-C) exceeded 900 microM, a value greater than that observed in CML-BC patients receiving ara-C alone (230 microM, n = 15, P less than 0.02). The present study shows the applicability of the alkaline elution method for the assay of DNA damage in vivo. The enhanced DNA damage after combined treatment with mitoxantrone and high-dose ara-C suggests a synergistic drug effect.

Adult↗

Phase I study of recombinant human granulocyte-macrophage colony-stimulating factor in patients with bone marrow failure and malignancy.

Twenty-five patients with malignancy and/or bone marrow failure were treated with recombinant human granulocyte macrophage colony-stimulating factor (rh GM-CSF) (specific activity 5 x 10(7) units/mg, purity greater than 95%) given by continuous intravenous infusion at various fixed dose levels (15-500 micrograms/m2/day), as part of a phase I study. Treatment was associated with marked increases in white blood cell counts (2-70 fold), consisting mainly of neutrophilic granulocytes. Significant increases were also observed in eosinophils, monocytes and lymphocytes. In addition six patients had multilineage responses characterized by increases in platelet counts (greater than 2 fold and greater than 100,000/mm3) and reticulocyte counts (greater than 2 fold). Three of these 6 patients did not require red cell or platelet transfusion for 17 to 37 weeks. Treatment also resulted in an increase in bone marrow cellularity and myeloid: erythroid cell ratio. The common side effects were constitutional symptoms and bone pain. These findings demonstrate that rh GM-CSF is well tolerated when given by continuous IV infusion and is a potent stimulator of hematopoiesis in vivo.

Bone Marrow↗

Aberrant expression of the K-ras proto-oncogene in B-cell malignancies.

The proto-oncogenes have the capacity for conversion to an oncogene that is capable of inducing or maintaining the transformed state when they are overly expressed or altered by mutation or rearrangement. To study the possible involvement of these genes in the neoplastic transformation of B-cell malignancies, we have analyzed their expression in 18 fresh samples obtained from the peripheral blood of patients with a variety of B-cell malignancies. A high-molecular weight c-k-ras transcript (5.2 kb) was detected in all samples including normal lymphocytes. In contrast, a low-molecular weight c-k-ras transcript (1.2 kb) was not detected in our control normal lymphocytes, but was found in 9 fresh samples. The 1.2 kb c-k-ras transcript was expressed 2-3-fold higher than the 5.2 kb c-k-ras transcript. C-h-ras (2.9 kb, 1.4 kb) was expressed at a low level in 4 and 13 samples, but not in normal lymphocytes. C-myc (2.3 kb) and c-raf (3.8 kb) were expressed in all samples including normal lymphocytes without significant variation in the level of expression. C-fos (2.2 kb) was expressed in 15 samples and normal lymphocytes with a wide range in the level of expression. C-myb (3.7 kb) and c-fes (2.7 kb) were expressed at a low level in 6 and 10 samples, respectively, including normal lymphocytes. C-sis (4.0 kb) was not detected in any sample including normal lymphocytes.

DNA↗

Cytogenetic pattern in acute myelogenous leukemia: a major reproducible determinant of outcome.

An analysis was conducted of clinical and laboratory variables associated with response to remission induction therapy and remission duration in 440 patients with acute myelogenous leukemia treated between 1975 and 1983. The complete remission rate was 259/440 (59%). Specific cytogenetic abnormalities such as t(8;21), t(15;17), and inv16 were found to be favorable for response to therapy and/or remission duration, whereas those with a normal (diploid) karyotype had an intermediate prognosis. All other karyotypic abnormalities were associated with lower response rates and short complete remission durations. The karyotypes were classified as favorable, intermediate, and unfavorable groups for response and remission duration after allowing for all the other observed clinical and laboratory values related to prognosis. The cytogenetic classification was prospectively validated in an independent test group of 130 patients treated between 1983 and 1986 and showed a consistent relationship to response and remission duration. Logistic regression and proportional hazard models developed from the initial 440 patients were prospectively evaluated in the test group of 130 patients. Clear stratifications of patients into good, intermediate, and poor risk groups were obtained in the prospective tests. The karyotype of the leukemia cells is an independent prognostic variable for response and remission duration in acute myelogenous leukemia.

Analysis of Variance↗

Detection of leukemic clone maturation in vivo by premature chromosome condensation.

The purpose of this study was to determine the feasibility of using the technique of premature chromosome condensation to detect the in vivo maturation of abnormal elements in patients with chronic myelogenous leukemia (CML), myelodysplastic syndrome, and acute leukemia. Patients were chosen for study if there were a clinical suggestion of in vivo maturation and a leukemic clone exhibiting a distinguishable karyotypic abnormality. Mature peripheral blood granulocytes were enriched by two-step Ficoll-Hypaque gradient sedimentation and fused with mitotic Chinese hamster ovary cells to induce the formation of prematurely condensed chromosomes (PCC). These PCC were then analyzed for chromosome number per cell (in the case of patients with a numerical abnormality) or by G-banding (in the case of specific translocations). Of 13 patients chosen for study, 12 showed karyotypic evidence for maturation of the abnormal elements in vivo. Maturation was observed in a number of clinical situations including before treatment in benign CML and myelodysplasia, after low-dose and high-dose chemotherapy in myelodysplasia and acute myelogenous leukemia (AML), and in remission. These results suggest that the technique of premature chromosome condensation can be a powerful tool in better understanding the biology of disease and mode of response to therapy in vivo in patients with leukemia and preleukemic syndromes, especially during treatment with agents thought to induce maturation of the leukemic elements.

Aneuploidy↗

Stimulation of hematopoiesis in patients with bone marrow failure and in patients with malignancy by recombinant human granulocyte-macrophage colony-stimulating factor.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multipotential hematopoietin. To assess the toxicity and biological activity of recombinant human GM-CSF (rhGM-CSF) in vivo, 25 patients with malignancy or bone marrow failure were treated with rhGM-CSF (specific activity approximately 5 x 10(7) U/mg) as part of a phase 1 trial. The treatment was administered by continuous intravenous (IV) infusion daily for 2 weeks at fixed dose levels and repeated after a 2-week rest period. Over the entire dose range tested (15 to 500 micrograms/m2/d), rhGM-CSF treatment was associated with dramatic increases (two- to 70-fold) in total leukocyte counts, which consisted predominantly of neutrophils, bands, eosinophils, and monocytes. Furthermore, six of the 14 patients with one or more cytopenias that received at least two cycles of treatment had multilineage responses characterized by twofold or greater increases in platelet count to a level above 100,000, twofold or greater increases in corrected reticulocyte count, and a reduced requirement for red cell transfusions. Three of these patients became independent of both red cell and platelet transfusions for 17 to 37 weeks of follow-up. Treatment was associated also with an increase in bone marrow cellularity and frequency of cycling progenitor cells. The treatment was well tolerated; side effects included constitutional symptoms and bone pain. These results demonstrated that rhGM-CSF has a significant impact on hematopoiesis in patients with advanced malignancy and also in patients with bone marrow failure.

Adult↗

An automated medical record system for a skilled nursing facility.

This paper reports on the development of an on-line automated medical record system suitable for nursing homes. The software was written in standard MUMPS (Massachusetts General Hospital Utilities Multi-Programming System) and is easy for the first-time user to operate. The data managed by the system may be divided into four major components, including text tables, the hierarchical problem dictionary, the patient admission data, and the care plan data. The system met all of the project's objectives and has been enthusiastically received by the nursing home staff.

Medical Records↗

Molecular analysis of chromosome 22 breakpoints in adult Philadelphia-positive acute lymphoblastic leukaemia.

The Philadelphia (Ph) translocation, t(9:22)(q 34:q11), is found in the majority of patients with chronic myelogenous leukaemia (CML) as well as in approximately 20% of adult acute lymphoblastic leukaemia (ALL) patients. The chromosome 22 breakpoint in CML has been localized within a restricted 5.8 kb segment of DNA known as the breakpoint cluster region (bcr). To investigate the chromosome 22 breakpoint in ALL, we analysed five adult Ph-positive ALL patients for bcr rearrangement. Rearrangement was detected within bcr in two patients. However, in one patient the break occurred 5' to the first exon of bcr and in two patients the bcr region was not involved. We conclude that the identical cytogenetic marker, t(9:22), may yield a different genomic configuration in ALL and CML.

Acute Disease↗

Comparison of results of salvage therapy in adult acute myelogenous leukemia.

The results of initial salvage therapy for refractory and relapsed acute myelogenous leukemia for patients treated between 1973 and 1986 have been evaluated. There was no significant improvement in complete remission (CR) rate and survival in patients treated between 1973 and 1980, and the second group between 1981 and 1986. The remission duration was slightly longer in the second time period than in the initial time period. A number of factors were associated with the probability of achieving a CR. The major factors were the age of the patient, duration of the initial CR, liver function test abnormalities, and white blood cell count.

Adult↗