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Biomedical subjects

M J Keating

Publications and source records attributed to M J Keating.

At least 271 records · Page 15Linked to original sources
PubMed1987

Visual experience and the maturation of the ipsilateral visuotectal projection in Xenopus laevis.

The effect of visual deprivation upon the maturation of the ipsilateral visuotectal projection has been studied in Xenopus laevis. This topographically ordered projection is polysynaptic. The first stage involves the retinal projection to the contralateral optic tectum. The tectum projects to the nucleus isthmi on the same side. The final stage is the crossed isthmotectal projection from the nucleus isthmi to the tectum ipsilateral to the eye. The topographic precision of connections at various points in this polysynaptic pathway has been investigated by quantifying single-unit and multi-unit receptive field sizes in the contralateral and ipsilateral visuotectal projections. Observations have been made on normal animals of different ages to plot the normal maturational course of events. The effects of visual deprivation on this maturational process has been studied. Between one week and one year after metamorphosis there is an increase in the precision of connections in both the contralateral and ipsilateral visuotectal projections. Visual deprivation had no effect upon the parameters of the contralateral visuotectal projection. Ipsilateral visuotectal single units in dark-reared animals had normal receptive field sizes. Ipsilateral multi-unit receptive fields in dark-reared animals were considerably larger than in normal animals. It was concluded that the effects of visual deprivation are limited to effects on the crossed isthmotectal component of the intertectal system. In this component, however, visual experience seems to play an important role in the normal development and modification of connections. It is suggested that visual experience is utilized to accommodate changes in the system required to respond to normal changes in interocular geometry that take place with development in Xenopus.

Animals↗
PubMed1987

Necrotizing dermatitis in patients receiving cancer chemotherapy.

Necrotizing dermatitis in patients being treated with cancer chemotherapeutic agents can be of several types. Microbial causes can include a variety of bacteria and fungi, the most common being Pseudomonas aeruginosa. Gangrene from occlusive causes is not uncommon among cancer patients with coexisting atheromatous, thromboembolic, or obliterative vascular disease. Toxic gangrene is most commonly caused by extravasation of intravenously administered cytotoxic antineoplastic drugs but has also been associated with the use of coumarin congeners and the bite of the brown recluse spider. Pyoderma gangrenosum is an idiopathic condition that has been reported in association with myeloproliferative disorders. Finally, necrosis can be caused by the neoplasm itself, when its growth is so great that blood vessels are compressed and ischemia of the surrounding tissue results.

Antineoplastic Agents↗
PubMed1987

External expressions of internal malignancy.

Paraneoplastic conditions are cancer-connected but are not produced as a direct effect of the tumor or metastasis. Some antedate the appearance of the internal malignancy; some run a course parallel to the tumor; some follow a pattern independent of the neoplasm. They occur in a small minority of patients with cancer and are, for the most part, of unknown cause. When an external disorder is present, it may act as a marker of hidden malignancy and thus contribute to its detection, or it may serve as an indicator of successful treatment. Many of the conditions described occur commonly without any underlying malignancy, but an unusual frequency of association with cancer makes their presence significant.

Acanthosis Nigricans↗
PubMed1987

Mucocutaneous granulocytic sarcomas of the head and neck.

Granulocytic sarcomas are malignant solid tumors composed of poorly differentiated myeloid cells that occur in association with myelocytic leukemia. The clinicopathologic characteristics of granulocytic sarcomas that presented in the oral mucosa and in the facial, scalp and neck skin of 8 patients in the acute phase of myelocytic leukemia are described and discussed. Although most of the tumors were demonstrably sensitive to cytosine arabinoside, alone or in combination with other antineoplastic drugs, the prognostic portent of these lesions was extremely poor.

Adult↗
PubMed1987

Intensive combination chemotherapy and interferons in the management of chronic myelogenous leukemia.

Compared to single-agent therapy with hydroxyurea or myleran (155 patients), intensive chemotherapy with vincristine, cytosine arabinoside, prednisone and cyclophosphamide (60 patients) or anthracyclines (37 patients) showed significant survival improvement overall (p less than 0.01) and among intermediate- and high-risk patients. Of 51 patients treated with human leukocyte alpha interferon (IFN-alpha), 36 (71%) had complete hematologic remission (CHR); 20 patients (39%) showed Ph suppression which was persistent in 13 for greater than 21 months. Survival was better in patients obtaining remission with IFN-alpha. Recombinant gamma interferon (IFN-gamma) was also active in chronic myelogenous leukemia. Therapy with combined IFN-alpha + IFN-gamma has been initiated. Compared to the expected survival, the observed survival is favorable for IFN-alpha and the combined chemotherapy and IFN-alpha programs. Future therapeutic trials will incorporate initial IFN therapy followed by cyclic intensive chemotherapy at 6-month intervals and IFN maintenance between chemotherapy cycles.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

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↗
PubMed1987

A strategy for evaluation of new treatments in untreated patients: application to a clinical trial of AMSA for acute leukemia.

This clinical trial (DT7995) was designed to evaluate amsacrine (AMSA) plus cytosine arabinoside (ara-C), vincristine, and prednisone (OAP) therapy in previously untreated patients with adult acute leukemia and to investigate a new strategy for assignment of patients to treatment using estimated probabilities of complete remission (PPR) based on six prognostic factors. In the first stage of the trial, patients with unfavorable prognosis (PPR less than .40) received AMSA-OAP for remission induction and patients with favorable prognosis (PPR greater than or equal to .40) received Adriamycin [Adria Laboratories, Columbus, OH] plus OAP (Ad-OAP). As AMSA-OAP was found to be promising in patients with unfavorable prognosis, it was administered to relatively more favorable patients (PPR less than .60) in the second stage of the trial and to all patients in the third stage. There were 242 patients entered into study; 134 received AMSA-OAP and 108 received Ad-OAP. Outcomes were compared with 242 paired patients who received Ad-OAP therapy from 1973 to 1977. The estimated complete remission rate in previously untreated adults with acute leukemia is 61% for patients receiving Ad-OAP (95% confidence interval, 59% to 64%). Overall, the survival experience for the 242 patients on DT7995 was significantly better than that in the control series (P = .03), but there was no strong statistical evidence (P = .10) that the 134 patients receiving AMSA-OAP had better survival than control patients receiving Ad-OAP, with a median of 32 v 21 weeks, respectively. It is concluded that AMSA-OAP is equivalent to Ad-OAP in the induction of complete remissions (estimated complete remission rate, 61%) and that assignment of patients to treatment based on predicted prognosis is an ethical and efficient strategy for the evaluation of new therapies in previously untreated patients with acute leukemia.

Acute Disease↗
PubMed1987

Central nervous system complications of a newly recognized subtype of leukemia: AMML with a pericentric inversion of chromosome 16.

Ten patients with acute myelomonocytic leukemia (AMML) and inversion of chromosome 16 who had CNS involvement were identified at M.D. Anderson Hospital between January 1972 and December 1984. The nervous system signs and symptoms were evaluated in detail. CT scans, CSF cytologies, and treatment modalities were reviewed. Two patients underwent biopsies of lesions that proved to be granulocytic sarcomas. AMML with inversion 16 carries a much higher (33%) incidence of CNS involvement in the form of leptomeningeal metastasis and/or granulocytic sarcoma than all other acute nonlymphocytic leukemias (5%). The reason for this appears to be related to the chromosomal aberration and not to prolonged survival.

Adult↗
PubMed1987

T-cell receptor gamma chain gene rearrangement in acute myelogenous leukemia--evidence for lymphoid lineage prematurity.

The T-cell receptor gamma chain (TcR gamma) gene is rearranged in early T-cell differentiation. However, rearrangement of the TcR gamma gene is not specific for T lineage since it has also been noted in B-cell neoplasia. TcR beta gene rearrangement and heavy chain immunoglobulin gene rearrangement have also been reported in acute myelogenous leukemia (AML). Because of the previous reports of lineage heterogeneity at the molecular level, we analyzed seven patients who met the standard criteria for AML by Southern blot hybridization with a TcR gamma gene probe, a TcR beta gene probe, and an immunoglobulin heavy chain JH gene probe. In two samples, the TcR gamma gene was rearranged. One of these two samples also had rearrangement of the immunoglobulin JH gene. None of the seven samples showed TcR beta gene rearrangement. The two samples with TcR gamma gene rearrangement also showed 25% and 80% of terminal deoxynucleotidyl transferase (TdT) positivity, respectively. Both samples expressed myeloid lineage-associated antigens without any lymphoid lineage-associated antigens. Our studies indicate that TcR gamma gene rearrangement is not specific for lymphoid lineage and the presence of TcR gamma and immunoglobulin JH gene rearrangements without expression of lymphoid lineage-associated markers supports the concept that there is lymphoid lineage prematurity in AML.

Gene Rearrangement, gamma-Chain T-Cell Antigen Rec↗
PubMed1987

Clinical investigation of human alpha interferon in chronic myelogenous leukemia.

Fifty-one patients with previously untreated or minimally treated chronic myelogenous leukemia in chronic phase received human alpha interferon 3 to 9 X 10(6) units intramuscularly (IM) daily until complete hematologic remission, then at doses ranging from 3 X 10(6) units every other day to 9 X 10(6) units daily. Forty-one (80%) patients achieved a hematologic response, 36 (71%) of them attaining a complete hematologic remission with normal peripheral WBC and differential counts. Responding patients showed continuous but slow normalization of several other blood and marrow parameters including platelet counts, serum lactic dehydrogenase and B12 levels, and marrow cellularity and maturation index. Suppression of the Philadelphia chromosome on serial cytogenetic studies of marrow metaphases was documented in 20 of the 36 patients who achieved complete hematologic remission (56%; 39% of total group), eight of whom (22%) had a decrease of the Philadelphia chromosome-positive metaphases to less than 35%. These changes were persistent for 6 months or longer in 18 patients, seven of whom had continuous suppression of the Philadelphia chromosome to less than 90% for a median of 30+ months (range 21+ to 39+ months). After a median follow-up period of 37 months, 25 patients remain in continued disease control with interferon therapy. The projected 3-year survival rate is 76%, with a yearly death rate of 6%, 9%, and 9% in the first 3 years. Response, Philadelphia chromosome suppression, and survival were significantly better among patients in the low-risk category compared to intermediate- and high-risk categories, as defined by a multivariate analysis-derived prognostic model. The projected 3-year survival rate was 94% for patients who achieved a complete hematologic remission on interferon therapy and 45% for those who did not. Thirteen patients have developed blastic crisis, six with lymphoid and three with undifferentiated morphology. We conclude that human leukocyte alpha interferon effectively controls chronic myeloid leukemia and allows reappearance of diploid hemopoietic cells in some patients.

Aged↗
PubMed1987

Old age: a sign of poor prognosis in patients with chronic myelogenous leukemia.

Fifty-four patients aged 60 years or older with a diagnosis of chronic myelogenous leukemia were referred to University of Texas M. D. Anderson Hospital between 1965 and 1982. Patients in this age group had a significantly shorter median survival than that of the 249 patients younger than 60 seen during the same period (26 vs 42 months; P = .01). Old age was associated with a higher incidence of poor performance status, hepatomegaly, and anemia. Fourteen other patient characteristics were correlated with poor prognosis, including black race, weight loss, symptoms, hepatomegaly, splenomegaly, anemia, thrombocytopenia or thrombocytosis, increased peripheral blast cells and promyelocytes or basophils, increased blasts or basophils in the bone marrow, decreased megakaryocytes, and additional cytogenetic abnormalities. A multivariate analysis that accounted for the interactions of these factors identified old age as being of primary adverse prognostic significance in patients with chronic myelogenous leukemia, suggesting a biologic difference in the disease in older patients. The poor prognosis in elderly patients receiving present available therapy justifies promising and well tolerated investigational approaches such as interferons in patients in this age group.

Age Factors↗
PubMed1987

Augmentation of antileukemia lytic activity by OKT3 monoclonal antibody: synergism of OKT3 and interleukin-2.

We have shown that short-term incubation (45 min) of peripheral blood lymphocytes of normal donors with OKT3 monoclonal antibody (MoAb), directed against T-cell-associated antigen CD3, resulted in an acquisition of lytic activity against fresh leukemic cells. Induction of such antileukemia activity was specific for OKT3, since Leu-1 MoAb (directed against another T cell surface molecule, CD5) did not induce a lytic effect. The OKT3-generated antileukemia effect was displayed against various types of leukemia including chronic myelogenous leukemia and acute myelogenous leukemia of various histological subtypes (M1, M2, M5). We furthermore demonstrated that OKT3 MoAb substantially enhanced leukemia killing by interleukin-2 (IL-2)-activated killer cells obtained from peripheral blood of patients with leukemia. Of most importance was the observation that the combined treatment of effector cells with IL-2 and OKT3 MoAb resulted in the highest levels of lysis of both autologous and allogeneic fresh leukemic cells that have been observed in leukemic patients to date. Of importance was to note that OKT3 treatment was effective in induction of cytotoxic activity also in patients whose effector cells were unresponsive to stimulation with IL-2 alone. All of these observations suggest that IL-2-activated and OKT3-MoAb-treated effector cells may represent the most aggressive population of antileukemia-directed killer cells and may play a significant role in the treatment of human leukemia.

Antibodies, Monoclonal↗
PubMed1987

Acute myelomonocytic leukemia associated with abnormalities of chromosome 16: a light and electron microscopic study.

We investigated the light and ultrastructural morphology of 37 patients with acute nonlymphocytic leukemia (ANLL) and inv(16)(p13q22) or del (16)(q22) with specific emphasis on the changes in the eosinophils (EOS). All but one of the 37 patients were classified as French-American-British M4 with eosinophilia (FAB M4-E) on the basis of the monocytoid nature of the leukemic cells and the presence of large EOS with interspersed basophilic-staining granules. A median of 92% of the blasts were peroxidase positive, and Auer rods were found in 71% of cases. Only 27% of the cases had sufficient alpha-naphthyl butyrate positivity to confirm the diagnosis of FAB M4, but electron microscopy demonstrated a sufficient monocytic component to support this classification in all cases examined. Electron microscopy also demonstrated nuclear blebs both in the blasts and notably, in the EOS of all cases examined (16 of 16). Nuclear blebs in EOS were found in only 1 of 13 cases of ANLL that showed eosinophilia but lacked abnormalities of chromosome 16. This case was also classified as FAB M4-E. The finding of nuclear blebs in EOS in FAB M4-E suggests that the EOS may be derived from the malignant clone in this leukemia. These blebs are also of diagnostic in value classifying a leukemia as FAB M4-E.

Adult↗
PubMed1987

Correlative patterns of neutrophil and platelet counts during very early remission of acute myeloblastic leukemia.

Patterns of recovery for peripheral blood neutrophils and platelets were analyzed in 65 patients with acute myeloblastic leukemia (AML) undergoing their first course of induction chemotherapy. Specifically, for every patient linear correlation coefficients (r values) were computed for neutrophils versus platelet counts every three days from Day 12 to 27 of therapy. Correlations were designated as "significant" if r greater than or equal to 0.82 (p less than or equal to 0.05). Patients who would enter complete remission with the first course of therapy were significantly more likely to have significant neutrophil-platelet correlations in the recovery phase than patients who did not achieve remission with the first course or who would have resistant disease (76% versus 20% and 76% versus 15%, respectively, both p less than 0.001). Although these data are preliminary and retrospective they nonetheless demonstrate a trend that may prove useful for patient monitoring if proven correct by formal studies. A prospective investigation examining neutrophil and platelet correlations within a defined period of early hematologic recovery is indicated to assess if such parameters have early prognostic value for the prediction of remission in individual patients receiving induction therapy for AML.

Bone Marrow↗
PubMed1987

Karyotype is prognostically more important than the FAB system's distinction between myelodysplastic syndrome and acute myelogenous leukemia.

Patients with myelodysplastic syndrome (MDS) and patients with acute myelogenous leukemia (AML) share certain specific karyotypes. Therefore, we compared the relative importance of karyotype and morphology (MDS vs. AML) in determining survival in these patients. We analyzed 768 patients with a banded karyotype who presented as either MDS or AML. Patients with "unfavorable" karyotypes had similarly short survivals regardless of whether they were classified as refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEBT), or AML. Patients with diploid karyotypes survived significantly longer, again with relatively minor differences between patients with RAEB, RAEBT, and AML. We conclude that classification of patients with excess myeloblasts in the marrow might more appropriately be based on cytogenetics than on the distinction between MDS and AML.

Anemia, Refractory, with Excess of Blasts↗