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Biomedical subjects

M J Keating

Publications and source records attributed to M J Keating.

At least 343 records · Page 19Linked to original sources
PubMed1983

Quantitative cytology in leukemia research.

A study was undertaken to determine the usefulness of flow cytometric analysis of bone marrow cells as an objective means for diagnosis, classification and prognosis in patients with leukemia. Abnormal DNA content as a marker of neoplastic disease was found in only 15% of 264 adult patients with acute leukemia (13% in AML, 26% in ALL/AUL). Alternative means of tumor cell detection in heterogeneous marrow samples include determination of nucleolar antigen density and double-stranded RNA content. Phenotypic characterization of leukemia subtypes can be afforded by RNA content analysis of acridine orange-stained cells, demonstrating significantly higher mean RNA content values in AML, compared to ALL/AUL. Cytokinetic parameters amenable to flow cytometric analysis include measurements of cell cycle compartment distribution by DNA content, of cycle traverse rate by BUdR-induced modification of fluorescence intensity of DNA specific dyes and of growth fraction employing the method of in situ DNA denaturation and subsequent acridine orange staining. Determination of cell cycle distribution and RNA content pretreatment and serially during remission induction in 82 patients demonstrated a significantly lower pretreatment biopsy S phase proportion in responding patients with AML compared to individuals failing treatment whereas an opposite trend was noted in patients with ALL/AUL. While of no prognostic impact pretreatment, serial determinations of the RNA content during the first chemotherapy induction course revealed significant differences between responding and failing patients with AML. Also, patients attaining remission demonstrated a rise in marrow biopsy S phase compartment size by day 10 to 14 of treatment, thus, predicting remission during marrow hypoplasia. We conclude that quantitative cytologic examination of marrow cells from patients with acute leukemia provides useful diagnostic and prognostic information that should aid in the stratification of patients with poor prognosis to receive new agents.

Adult↗
PubMed1983

Phase II trial of mitoxantrone in refractory acute leukemia.

Mitoxantrone was administered to 41 adults with refractory acute leukemia. The initial dose employed was 4 mg/m2/day X 5 days. Eventually a starting dose of 10 mg/m2/day X 5 days was used, with some patients receiving a subsequent course at 12 mg/m2/day X 5 days. Three patients had a complete response, one a partial response, and one hematologic improvement. Although antileukemia effect was more frequent at the higher doses, so was death following treatment.

Acute Disease↗
PubMed1982

Improved prospects for long-term survival in adults with acute myelogenous leukemia.

An improved complete remission rate in acute myelogenous leukemia (AML) has been noted since cytarabine and anthracyclines were introduced into clinical practice. Forty-one (9%) of 457 patients with AML treated between 1965 and 1976 have survived more than five years. The proportion of five-year survivors for patients treated between 1973 and 1976, 1970 and 1972, and 1965 and 1969 were 11.8%, 8.8%, and 1.8%, respectively. The major factor influencing five-year survival was whether or not patients were treated with cytarabine alone or combined with an anthracycline. Thirty-six (17%) of the 207 complete responders remained in continuous complete remission for more than five years. Twenty-four of the 36 patients who are in remission for more than five years have not been receiving chemotherapy for more than five years and are considered potentially cured.

Adolescent↗
PubMed1982

A prognostic factor analysis for use in development of predictive models for response in adult acute leukemia.

The pretreatment characteristics of 325 adults with acute leukemia who were treated at the M. D. Anderson Hospital between 1973 and 1977 have been evaluated to assess their value as prognostic indicators. The patient population includes all patients treated with an anthracycline (Adriamycin or rubidazone), cytosine arabinoside, vincristine, and prednisone during the time period. Most patients had one of the variants of acute myelogenous leukemia (75%), and the remaining patients had acute lymphoblastic leukemia (16%) or undifferentiated leukemia (8%). Twenty-one factors were found to be significantly associated with probability of obtaining a complete response. In addition to characteristics previously known to provide prognostic information such as age, temperature status at the start of treatment, morphology, the presence of Auer rods, sex, and hemoglobin level, we identified the presence of a documented antecedent hematologic disorder and the finding of insufficient metaphases on cytogenetic analysis using the squash technique as being major prognostic variables. In addition, the pretreatment biochemical characteristics of hypoalbuminemia and elevated blood urea nitrogen and creatinine were found to adversely influence prognosis. The prognostic significance of factors such as the leukocyte count and platelet count, identified in earlier studies, was not confirmed in this group of patients. From this natural-history analysis predictive models for response have been developed using multivariate logistic regression techniques. One of these models has been used to evaluate the effect of morphology, treatment, and cytogenetic pattern on response to the combination of drugs used.

Acute Disease↗
PubMed1982

Prediction of remission in adult acute leukemia: development and testing of predictive models.

Logistic regression methods were applied to derive a set of models relating achievement of CR to prognostic characteristics in a group of 300 adult acute leukemia patients treated with cytosine arabinoside, vincristine, and prednisone combined with adriamycin (ADOAP) or rubidazone (ROAP). These models were tested prospectively in an independent group of 107 subsequent patients treated with ADOAP or ROAP therapy, by comparing observed outcomes to predictions of response based on the models. Several models were able to identify subgroups of patients with good, intermediate, and poor prognoses. A model regarded as clinically useful and which provided a good fit to both the population from which it was derived and the test population included the pretreatment factors age, history of an antecedent hematologic disorder, temperature, blood urea nitrogen, hemoglobin, and liver size.

Acute Disease↗
PubMed1982

Properties of the receptive fields of frog retinal ganglion cells as revealed by their response to moving stimuli.

Quantitative mapping of the excitatory receptive fields of frog retinal ganglion cells revealed that the precise spatial position and locus of maximal activity within the excitatory receptive field were dependent upon the exact sequence with which the moving stimulus scanned the region of visual space in which the excitatory receptive field was embedded. A first-order asymmetry dependent upon the direction from which the moving stimulus entered the excitatory receptive field was noted. A second-order asymmetry, orthogonal to the first and sensitive to the direction in which a moving stimulus systematically traversed successive columns with in the excitatory receptive field was also described. These findings indicate that complicated interactions, both excitatory and inhibitory, occur between component parts of the receptive field in the frog retina.

Animals↗
PubMed1982

Retrospective analysis of 158 cases of adult acute leukaemia: factors influencing prognosis and treatment response.

Discriminant and regression analyses were employed to determine the influence of a large number of clinical and laboratory indices on outcome of treatment in a series of 158 adults presenting with acute leukaemia between 1970 and 1977. Induction therapy had been most commonly cytosine arabinoside plus daunorubicin, vincristine and prednisolone. This induced complete remission in 42% of non-lymphoblastic, and in 58% of lymphoblastic plus undifferentiated leukaemias. Some induction failures who had non-lymphoblastic leukaemia were treated with cytosine arabinoside plus 6-thioguanine, which induced remissions in 46%. Advanced age was the factor most strongly associated with failure either to achieve or to sustain complete remission. Thrombocytopenia, promyelocytic leukaemia, high percentage of marrow blasts, and absence of metaphases in marrow cytogenetic preparations were also associated with poor survival. A number of other factors which appeared to be associated with poor prognosis were found by the analysis to lack significance as independent variables.

Adult↗
PubMed1982

Modulation of 9-beta-D-arabinofuranosyladenine 5'-triphosphate and deoxyadenosine triphosphate in leukemic cells by 2'-deoxycoformycin during therapy with 9-beta-D-arabinofuranosyladenine.

The effect of the adenosine deaminase inhibitor, 2'-deoxycoformycin, on cellular nucleotides during therapy with continuous infusion of 9-beta-D-arabinofuranosyladenine (ara-A) has been investigated. In three courses of treatment using increasing doses, the active 5'-triphosphate of ara-A, 9-beta-D-arabinofuranosyladenine 5'-triphosphate (ara-ATP) accumulated in leukemic cells and erythrocytes from a patient treated for acute lymphocytic leukemia in proportion to the dose of ara-A. The cellular ara-ATP concentration increased more than 5-fold after the injection of a single, nontoxic, but pharmacologically active dose of 2'-deoxycoformycin 24 hr after initiation of ara-A infusion. However, this response was associated with a concomitant increase in the cellular deoxyadenosine triphosphate concentrations to levels equal to or greater than those of ara-ATP throughout the three treatment courses studied. Consistent with previous results using cell-free systems, it was demonstrated that a competitive relationship exists between deoxyadenosine triphosphate and ara-ATP for the inhibition of DNA synthesis in cultured human lymphoblastoid cells and that the ratio of the cellular concentrations of these nucleotides could predict the extent of inhibition of DNA synthesis. Application of this rationale to the nucleotides in the leukemic cells of the patient suggested that administration of 2'-deoxycoformycin may create a cellular biochemical milieu that could be antagonistic to the inhibition of DNA synthesis by ara-ATP.

Adult↗
PubMed1982

Causes of initial remission induction failure in acute myelogenous leukemia.

One-hundred and sixty-one of 378 previously untreated patients with acute myelogenous leukemia (AML) failed to enter complete remission with a combination of anthracycline, cytosine arabinoside, vincristine, and prednisone between 1973 and 1979. Thirty-six of the failing patients (22%) were considered chemotherapy failures. As in the past, the remainder failed largely because of death from infection. However, despite the routine use of prophylactic platelet transfusions, hemorrhage was a major cause of death in 33%. Thirty-seven percent of the fatal infections were due to fungi and the incidence of fungal infection was as high during the second week of treatment as later. Age greater than 50 yr predisposed to fatal infection but not chemotherapy failure, while the presence of an antecedent hematologic disorder increased the risk of both fatal fungal infection and resistance to chemotherapy. Patients with an initial white blood cell count of greater than or equal to 25000/microliter were more likely to die of hemorrhage at all times during treatment. Improvement in supportive care remains crucial if improved complete rates are to be forthcoming in previously untreated patients.

Adult↗
PubMed1982

Evaluation of AMSA in previously treated patients with acute leukemia: results of therapy in 109 adults.

AMSA was evaluated in the treatment of 109 adults with previously treated acute leukemia. Of the 102 evaluable patients, 82 had AML, 17 ALL, and 3 CML in blastic phase. A number of different dose schedules of AMSA were explored, and we conclude that the optimum dose of AMSA for remission induction in acute leukemia is 120 mg/sq m/day for 5 days. Complete remissions were observed in 23 (28%) patients with AML and in 1 patient with ALL. Patients who achieved complete remission were maintained on AMSA using a dose of 30-40 mg/sq m/day for 5 days repeated at 4-wk intervals. The median duration of complete remission was 12 wk (3-59 wk), and the responders survived significantly longer than the failures (27 wk versus 8 wk, p = 0.002). The side effects associated with AMSA therapy included mild nausea and vomiting, stomatitis, diarrhea, phlebitis, alopecia, and myelosuppression-related infections. Our results indicate that AMSA is a useful new antileukemic agent for the treatment of relapsed acute leukemia and appears to have activity comparable to that of the currently available drugs, such as cytarabine and the anthracycline antibiotics.

Acute Disease↗
PubMed1981

Plasticity in a central nervous pathway in xenopus: anatomical changes in the isthmotectal projection after larval eye rotation.

In this paper we present evidence that early eye rotation in Xenopus leads to anatomical rearrangements in a portion of the binocular visual system. In the past, electrophysiological mapping had shown that the topography of the ipsilateral visuotectal projection is changed by such eye rotation and that this change requires visual experience. However, knowledge of the anatomical basis for this electrophysiological change was lacking. The identification of the nucleus isthmi as a link in the projection has allowed us to study the topography of the ipsilateral system by use of horseradish peroxidase. We present data showing that early eye rotation alters the topography of the crossed isthmotectal projection. These results demonstrate that the orientation of a topographically organized projection can be changed by procedures which do not involve direct manipulation of the source, pathway, or target of the projection.

Animals↗
PubMed1981

A four-year experience with anthracycline, cytosine arabinoside, vincristine and prednisone combination chemotherapy in 325 adults with acute leukemia.

Combination chemotherapy with an anthracycline, Adriamycin or rubidazone, cytosine arabinoside, vincristine and prednisone resulted in a complete remission rate of 62% in 325 consecutive unselected adults with acute leukemia. The results by morphologic categories were 58% for acute myelogenous leukemia (AML), 70% for acute undifferentiated leukemia (AUL), and 77% for acute lymphoblastic leukemia (ALL). The median survival was 43 weeks. Ten percent of all patients are projected to be alive and in remission at five years. The median remission duration for the whole group was 51 weeks, durations being significantly longer for AML (60 wks) than ALL (30 wks) and AUL (21 wks). Central nervous system involvement was uncommon in AML (4%), but much more common in patients with AUL (37%) and ALL (32%). One in five complete responders with AML is projected to be in their first remission at five years off all chemotherapy. Age, sex, morphology, cytogenetic pattern, temperature of presentation, and presence of a documented preceding hematologic abnormality are found to be significant variables for response and survival.

Adolescent↗
PubMed1981

Chemoimmunotherapy of adult acute leukemia.

Sixty-two adult patients with acute myeloid leukemia were treated with a chemotherapy program of Adriamycin, Cytosine Arabinoside (Ara-C), vincristine, and prednisone (Ad-OAP). Immunotherapy with BCG by scarification was administered before and/or during remission induction therapy. Maintenance chemoimmunotherapy consisted of Ara-C, vincristine, prednisone, and BCG. Patients still in remission after 12 months received late intensification chemotherapy for three courses before discontinuing chemotherapy. Forty-four (71%) patients achieved a complete remission (CR). The CR rate for patients less than 50 years of age ws 84% (32/38). Age was strongly predictive for response and survival. An additional 14 patients with acute lymphoid leukemia were treated with the same program; ten patients responded, all have relapsed and died. Nine patients with AML remain alive 4 1/2-6+ years from diagnosis.

Adolescent↗
PubMed1981

Antibody responses of remission leukemia patients receiving active specific and nonspecific immunotherapy.

A solid-phase radioimmunoassay was utilized to evaluate the antibody response of 21 acute myelogenous leukemia (AML) patients to active specific immunotherapy with either pooled allogeneic AML blast cells or leukemia-associated antigen (LAA), admixed with BCG cell-wall skeleton (CWS). Five of 13 patients treated with LAA had a significant antibody response to LAA after immunotherapy. Antibody response correlated with an increased remission duration (159+ vs. 75+ weeks) and an increased survival (164+ vs. 98+ weeks). Two of eight patients treated with cells responded to LAA, and three patients had initially high anti-LAA antibody levels. In the total study, eight of 11 patients surviving longer than 2 1/2 years and six of seven patients maintaining a complete remission longer than 2 years were antibody responders. Neither protocol induced significant antibody to a normal spleen extract, BCG-CWS, or a measles recall antigen. However, five of seven patients with initially high levels of antibody to BCG (following weekly BCG scarification) were long-term survivors. These data suggest that the humoral immune response to immunotherapeutic agents may be a useful parameter for monitoring immunotherapy of AML patients.

Antibodies, Neoplasm↗