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Biomedical subjects

M Keating

Publications and source records attributed to M Keating.

At least 163 records · Page 9Linked to original sources
PubMed1989

Association of granulocytosis with poor prognosis in patients with acute myelogenous leukemia and translocation of chromosomes 8 and 21.

Forty-three patients with acute myelogenous leukemia (AML) and a translocation 8;21 were reviewed. The patients' median age was 30 years, and 62% were men. Twenty-three patients (53%) had loss of a sex chromosome and ten (23%) had other chromosomal abnormalities in addition to the 8;21 translocation. Complete remission (CR) with induction chemotherapy was achieved in 40 patients (93%). The median CR duration was 18 months (range, 1 to 137+ months). Median survival time was 17 months (range, 0.5 to 138+ months) with a 3-year survival rate of 31%. Twenty-three patients (53%) relapsed between 1 and 58 months after entering remission with reinduction therapy resulting in 8 CRs (35%). Thirteen characteristics were examined for an effect on survival. The most striking finding was a significant association between elevated absolute granulocyte count and poor survival (P = .002). WBC count greater than 10,000/microL was also associated with shorter survival (P = .05). Patient age, albumin level, and platelet count showed trends for survival association. Although patients with AML and t(8;21) are regarded as a favorable group with respect to survival, we found a subset of patients who do very poorly. Intensive or more investigational approaches in first remission should be considered for these patients.

Adolescent↗
PubMed1989

Treatment of systemic fungal infections with liposomal amphotericin B.

Forty-six patients with systemic fungal infections were treated with liposomal amphotericin B. Twenty-one patients had disseminated candidiasis, 19 had aspergillosis, and the rest had a variety of other fungal infections. Forty patients failed to respond to conventional amphotericin B therapy, and 6 patients were given liposomal amphotericin B because conventional amphotericin B caused severe side effects. Twenty-four patients had a complete response, and 22 patients failed to respond. No short- or long-term toxic reactions were observed. The acute side effects such as fever, chills, and potassium loss were infrequent and milder than those commonly observed with conventional amphotericin B. No chronic renal, hematologic, or central nervous system side effects were observed. Liposomal amphotericin B therapy was effective and less toxic than conventional amphotericin B therapy.

Adolescent↗
PubMed1988

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↗
PubMed1988

Abnormalities of dynamic ventricular shape change in patients with aortic and mitral valvular regurgitation: assessment by Fourier shape analysis and global geometric indexes.

The normal cardiac cycle is associated with dynamic changes in left ventricular shape, which can be disturbed in disease states. To assess the influences of diastolic volume, percent ejected volume, and abnormalities of acute or chronic systolic loading on general and detailed chamber geometry, we studied dynamic shape change recorded by x-ray contrast ventriculography in both normal patients and those with aortic (AR) or mitral (MR) valve regurgitation. While both lesions increased diastolic volume, the character of load throughout ejection differed markedly. Detailed cavity geometry was assessed by a Fourier analysis technique and general shape by eccentricity and circularity indexes. Normal hearts, showed increased systolic elongation by all indexes. AR patients displayed a similar rise in eccentricity during ejection; however, the extent of shape change when measured by Fourier and circular indexes was reduced. In contrast, MR patients displayed enhanced systolic shape change, particularly in chamber elongation. Neither simple eccentricity of circular indexes adequately differentiated these shape abnormalities, whereas detailed Fourier geometric analysis precisely characterized the abnormalities of shape change in these two diseases. Relations between the extent of shape change and ejected volume for each patient group revealed significantly more systolic deformation with a different shape versus volume relation for the MR hearts as compared with AR and controls. Thus, while dynamic left ventricular shape is certainly influenced by the extent of volume change, it also varies independently from volume related to the specific nature of loading during ejection.

Algorithms↗
PubMed1988

A comparison of marrow transplantation with chemotherapy for adults with acute leukemia of poor prognosis in first complete remission.

From July 1980 to November 1985, 109 patients with acute myelogenous and lymphoblastic leukemia who had reached a complete remission (CR) following induction treatment were assigned to a study comparing marrow transplantation with chemotherapy as a postremission treatment. Sixty-nine patients did not have a human leukocyte antigen (HLA)-identical donor, and therefore served as chemotherapy controls; 40 patients had HLA-identical donors, and therefore were assigned to the transplant arm. Of these, 23 were transplanted in first remission and 17 were not. Ten of these 17 were subsequently transplanted in relapse. Initially, only patients with poor prognosis determined by a predictive model were entered into the study. Subsequently, patients with moderately poor prognosis were admitted. Comparing the chemotherapy group with the patients transplanted in first CR, significant control of leukemia relapse in transplanted patients was seen in the subgroup with acute myelogenous leukemia (AML) (P less than .1), and acute lymphoblastic leukemia (ALL) (P less than .01), in the poor (P = .01) and intermediate subgroup (P = .01), and in the good-prognostic groups (P = .05). The survival was affected significantly in only the poor and intermediate subgroups. The use of predictive models might help to select patients for whom bone marrow transplantation is appropriate in first remission and those for whom bone marrow transplantation can be left as the initial treatment of relapse. Predictive models could further be helpful in comparing studies performed at different transplant centers.

Adolescent↗
PubMed1988

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↗
PubMed1988

Cytogenetic association and prognostic significance of bone marrow blast cell terminal transferase in patients with acute myeloblastic leukemia.

One hundred ninety-two patients with previously untreated AML had TdT studies performed on their presenting BM aspirate specimens. Thirty-seven patients (19%) had greater than 5% TdT-positive (TdT+) blasts in their BM, as determined by an indirect immunofluorescence technique. CR rates were similar in both groups of patients (20/37 vs. 97/155, p = not significant) as were remission durations and median survivals. In the subset of patients younger than 60 years, patients with TdT+ blasts had an increased median survival (110 vs. 54 weeks, p = 0.1) compared with those having TdT- blasts. Six of 37 patients with TdT+ findings had t(8;21) translocations compared to 5 of 155 with TdT- findings (16% vs. 3%, p less than 0.01). Patients with more than 50% BM blast cells showing TdT positivity at diagnosis tended to be younger than those with TdT- (mean age 30.5 years and 50.3 years, p = 0.04). The presence of TdT+ blast cells in the initial marrow in patients with AML may be associated with specific cytogenetic abnormalities and may identify subsets of patients who have improved prognoses.

Bone Marrow↗
PubMed1988

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↗
PubMed1988

Complications of hypospadias repair.

Hypospadias is one of the more common and one of the most challenging problems in urologic surgery. The past two decades have ushered in an era of new operations and variations of older ones, which, when coupled with technical advancements and improvements in management, have redefined the aims of the surgeon, who now strives to create a "normal" penis with a minimum of complications. Minimization of complications is contingent on selection of an operation properly tailored to the individual's anatomy. To this end, the surgeon's armamentarium must include a variety of repairs and familiarity with the limitations and potential complications inherent in each. After describing the principles of surgical selection, technique, and postoperative management used in our institution, this article deals primarily with the avoidance and management of the immediate and long-term complications of hypospadias surgery.

Bandages↗
PubMed1987

Effects of recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes.

The myelodysplastic syndromes are characterized by ineffective hematopoiesis and refractory cytopenias. In an attempt to improve hematopoiesis, we administered recombinant human granulocyte--macrophage colony-stimulating factor (GM-CSF) to eight patients with myelodysplastic syndrome, as part of a Phase I trial. The GM-CSF was given by continuous intravenous infusion daily for two weeks and then again after a two-week rest period. Over the entire dose range tested (30 to 500 micrograms per square meter of body-surface area), treatment was associated with marked increases in peripheral-blood leukocytes (5- to 70-fold), including granulocytes (5- to 373-fold), in all eight patients. The absolute number of monocytes, eosinophils, and lymphocytes increased in all patients. Three of eight patients also had 2- to 10-fold increases in platelet counts and improvement in erythropoiesis, with the result that two of three patients who had required red-cell and platelet transfusions no longer needed them (at 20 to 27 weeks of follow-up). Treatment was also associated with increased marrow cellularity and a decreased percentage of blasts in the bone marrow of patients with excess blasts, resulting in an increase in the ratio of differentiated myeloid cells to immature myeloid cells. We observed relatively few side effects, but bone pain was dose-limiting when it was associated with high white-cell counts. Our results showed that GM-CSF is a potent stimulator of hematopoiesis in vivo and may produce hematologic improvement in the short term (8 to 32 weeks of observation) in patients with myelodysplastic syndrome. More experience, with longer follow-up periods, will be necessary to assess the long-term safety and efficacy of this new treatment.

Adult↗
PubMed1987

High dose cyclophosphamide, BCNU, and VP-16 (CBV) as a conditioning regimen for allogeneic bone marrow transplantation for patients with acute leukemia.

A high dose combination chemotherapy regimen (CBV) consisting of cyclophosphamide (1.5 gm/m2 day 1 to day 4); BCNU (300 mg/m2 day 1) and etoposide (100 mg/m2 every 12 hours for 6 doses), followed by bone marrow transplant from human leukocyte antigen (HLA) identical sibling donors, was evaluated in 29 patients in whom acute leukemia was in relapse or remission. Engraftment of donor cell type occurred in all but one of 21 patients, in whom marker differences between donor and recipient were established. Two of 11 patients transplanted during relapse of the disease, lived beyond 1 year after bone marrow transplantation. One patient died free of leukemia, 41 months after transplantation of meningitis. Two of seven patients transplanted during the second remission of the disease, are alive and free of leukemia at 42+, and 8+ months. All patients transplanted during the third or fourth remission of the disease have died from either a further relapse, or transplant related causes. The low incidence of organ toxicity with CBV allows for further dose escalation of its drug components.

Acute Disease↗
PubMed1987

Therapy of chronic myelogenous leukemia.

While the demonstrated antiviral, antiproliferative, and immunomodulatory properties of interferons have led to a number of theories regarding their potential use in treating individuals with chronic myelogenous leukemia (CML), their limited availability has prevented thorough clinical investigation. However, in 1980, successful cloning of the mature human alpha-A interferon led to the production of large quantities of bacterially synthesized human alpha-A interferon, now designated interferon alfa-2a (Roferon-A, Hoffmann-La Roche, Nutley, NJ). This abundance of alfa-2a made possible clinical studies of alpha interferon's capacity to suppress CML Philadelphia (Ph1) clones as well as restore the cells with normal karyotype. The data resulting from these clinical trials indicate that interferon alfa-2a is effective in inducing hematologic remissions in the majority of minimally treated, benign-phase CML, Ph1-positive patients. In some of the patients, treatment resulted in Ph1 chromosome suppression in the bone marrow and in the emergence of cells with a normal karyotype.

Antineoplastic Agents↗
PubMed1987

Clinical and prognostic features of patients with Philadelphia chromosome-positive chronic myelogenous leukemia and extramedullary disease.

Twenty-four patients who developed extramedullary disease during the course of Philadelphia chromosome-positive chronic myelogenous leukemia are described. The most frequent sites of extramedullary disease were lymph nodes (54%), bone (37%), and skin and soft tissue (29%). The appearance of extramedullary disease was associated with a high incidence of other features of accelerated disease (37%) and with cytogenetic clonal evolution (62.5%). The median time from extramedullary disease to blastic crisis was 4 months, and the median survival was 5 months. At the time of analysis, 23 patients have died, 16 after evolving into blastic crisis, and 7 from progressive disease without satisfying the criteria of medullary blastic crisis. This study confirms the importance of extramedullary disease as a sign of poor prognosis in chronic myelogenous leukemia, and the need for alternate therapies when such an event develops.

Bone Neoplasms↗
PubMed1987

DNA aneuploidy in adult acute leukemia.

Using flow cytometric techniques, we determined DNA ploidy levels in the bone marrow of 318 successive adult patients with newly diagnosed acute leukemia. Overall, 26% exhibited DNA stem line abnormalities, usually with a 10%-15% DNA excess, regardless of morphologic diagnosis. DNA aneuploidy was seen most frequently in patients with a hyperdiploid chromosome number and karyotype instability (50%), but was also present in a third of patients with chromosomal translocations and in 20% of patients with a normal diploid karyotype. Thus, among 73 patients with DNA aneuploidy, quantitatively concordant karyotype abnormalities were observed in almost 40% of patients; the discrepancy between DNA content and chromosome number in the remaining patients may reflect differences in the cell cycle position of target cells in G1/0 phase or mitosis, respectively. Cytogenetics affected treatment outcome in acute myelogenous leukemia (AML) with more favorable short- and long-term prognosis among patients with translocations compared with those with numeric abnormalities. The presence of an abnormal DNA stem line, among AML patients with translocations, identified a favorable subgroup with significantly longer remission duration and survival (25 and 26 months versus 18 and 13 months, respectively). In addition, the prognostic implications of DNA aneuploidy in AML were age-dependent, in that favorable effects among patients with translocations and unfavorable effects among those with numeric abnormalities or diploid karyotypes were most obvious in young and not in older patients (greater than or equal to 40 years). In adults with ALL, DNA aneuploidy was associated with shorter survival (15 versus 39 months in the diploid group), an observation that is distinctly at variance with recent findings in childhood ALL. Our results indicated that DNA flow cytometry was complementary to standard cytogenetics for the detection of genomic abnormalities; and DNA aneuploidy emerged, like in children but not in adults with ALL, as a new favorable prognostic feature in a subgroup of adults with AML, the biologic basis of which remains to be determined.

Adult↗
PubMed1987

Amphotericin B or ketoconazole therapy of fungal infections in neutropenic cancer patients.

Fungal infections in neutropenic cancer patients have increased in frequency and constitute an important cause of morbidity and mortality. Empiric antifungal therapy is often administered to those patients who have failed to respond to antibacterial antibiotics. We conducted a prospective, randomized trial of amphotericin B and ketoconazole for 172 neutropenic cancer patients with presumed or proven fungal infections. Overall, amphotericin B and ketoconazole were equally effective. Amphotericin B may have been more effective than ketoconazole for the treatment of pneumonia. Also, five of eight Candida tropicalis infections treated with amphotericin B responded, whereas all eight infections treated with ketoconazole failed to respond (P = 0.03). Response rates for localized fungal infections were similar with both drugs. Ketoconazole should not be used as empiric antifungal therapy at institutions where there is a high frequency of infections caused by Aspergillus spp. or C. tropicalis because this agent lacks activity in vitro against these species.

Adolescent↗
PubMed1987

Hematologic response of four patients with smoldering acute myelogenous leukemia to partially pure gamma interferon.

In vitro and in vivo studies were conducted to obtain basic information on the activity of gamma interferon (IFN-gamma) in acute myelogenous leukemia (AML). In a selected case of AML, recombinant IFN-gamma, but not IFN-alpha, induced differentiation of primary leukemic blasts in vitro. Similarly, IFN-gamma inhibited leukemic colony formation in vitro. This contrasted with IFN-alpha which was inactive. In one case of AML (M2), partially purified IFN-gamma given intravenously caused a shift of the WBC profile from immature blasts to maturing myeloid cells and neutrophil granulocytes. Intravenous IFN-gamma treatment of another patient who had AML as a second malignancy resulted in a complete hematologic remission, normalization of marrow granulocyte-macrophage colony-forming cell in vitro growth, and conversion of marrow cytogenetics from 95% hyperdiploid clone with complex abnormalities into 100% diploid. The results indicate a potential use of IFN-gamma in the treatment of selected patients with AML and the possibility of in vitro pretreatment evaluation of these patients' leukemic response to IFNs.

Adult↗