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Biomedical subjects

M J Keating

Publications and source records attributed to M J Keating.

At least 361 records · Page 20Linked to original sources
PubMed1981

Natural history of central nervous system acute leukemia in adults.

Central nervous system (CNS) involvement occurred in 45 of 222 (20.3%) leukemic adults achieving bone marrow (BM) complete remission (CR), including 12 of 23 (52%) acute undifferentiated leukemia (AUL), 12 of 32 (39%) lymphoma leukemia, 5 of 26 (19%) acute lymphoblastic leukemia, and 16 of 142 (11%) acute myelogenous leukemia. Risk factors for CNS disease were lactic dehydrogenase (LDH) greater than or equal to 25,000/mm3. AUL morphology, age less than 20 years, and extramedullary involvement were most significant. Pattern of CNS involvement varied with morphology. Survival after CNS relapse depended most on BM status and symptoms. Duration of CNS CR was longest for asymptomatic patients with low CSF cell counts. Also important were duration of first BM CR, ease of achievement of initial BM CR, and leukocyte count (original and at most closely antecedent BM involvement), reflecting the common origin of BM and CNS leukemic cells. Central nervous system relapse generally did not shorten BM CR or survival, although early primary CNS relapse was associated with early BM relapse.

Acute Disease↗
PubMed1981

Chemotherapy-induced oral mucositis in adult leukemia.

Oral mucositis directly attributable to antileukemia chemotherapy occurs in almost 20% of adults undergoing such treatment. Although the mucositis is self-limited when uncomplicated by infection, the attendant extreme discomfort may produce physical and psychologic obstructions to continued anticancer treatment. Because of the ever-present risk of serious infection, drug-induced stomatitis constitutes a threat to the patient that must be kept under constant surveillance and control.

Adult↗
PubMed1981

Treatment of patients over 50 years of age with acute myelogenous leukemia with a combination of rubidazone and cytosine arabinoside, vincristine, and prednisone (ROAP).

We administered a combination of rubidazone, cytosine arabinoside, vincristine, and prednisone (ROAP) to 91 patients with acute myelogenous leukemia who were 50 yr of age or older. These patients had been identified in previous studies to be a group with a relatively poor prognosis. One-third of the patients had an antecedent hematologic disorder prior to treatment. Forty patients (48%) obtained a complete hematologic and clinical remission. A history of an antecedent hematologic disorder, male sex, and absence of Auer rods were adverse factors for achieving remission in this older population. More than half of the patients achieved remission in one course. The major cause of failure to obtain a remission was death due to infection, 40% of which were caused by fungi. Resistance to chemotherapy, although uncommon, was noted more frequently in patients with an antecedent hematologic disorder. Univariate and multivariate prognostic factor analysis was used to compare these patients with a historical control group treated with a program in which adriamycin was used instead of rubidazone (AdOAP). No significant difference in remission rate was detected. Cyclocytidine was used as a maintenance agent in this study, and while the median remission duration was only 37 wk, 30% of patients are expected to be in remission for 2 yr. Chemotherapy programs combining an anthracycline with cytosine arabinoside, given to older patients in similar fasion to younger patients will achieve remissions in one-half of a group of older patients. These remissions are of comparable quality to those of younger patients. Mathematical models derived from analysis of prognostic factors are of use in identifying patients likely to fail these programs who are in need of innovative approaches to treatment.

Aged↗
PubMed1981

Asparaginase and methotrexate combination chemotherapy in relapsed acute lymphoblastic leukemia in adults.

We have treated 37 adults with acute lymphoblastic leukemia (ALL), who have relapsed on previous intensive chemotherapy, with a combination of L-asparaginase and methotrexate (MTX) +/- ifosfamide. The initial study included 26 patients who received the two-drug combination of L-asparaginase and MTX given sequentially. Of the 26 patients, 15 (58%) achieved complete remission (CR), while 3 patients had a partial remission (PR), resulting in an overall response rate of 69%. The median duration of CR was 17.5 weeks. The median survival of complete responders was 39 weeks compared with 10 weeks for failures (P=0.001). The regimen was generally well tolerated and it was possible to give MTX doses of up to 400 mg/m2 with minimal myelosuppression, and severe stomatitis was infrequent. A further study involved the use of this regimen combined with ifosfamide in 11 patients. In this continuing study, there were six CR's (55%) and two PR's, with an overall response rate of 73%. The median duration of CR was 14+ weeks, and the median survival was 40+ weeks. Combination chemotherapy with asparaginase and MTX is effective in inducing remission in adults with ALL in relapse. It should now be considered for inclusion as part of induction therapy of previously untreated adults with ALL.

Adolescent↗
PubMed1981

Pharmacokinetics of [14C]methylglyoxal-bis-guanylhydrazone) in patients with leukemia.

Methylglyoxal-bis(guanylhydrazone) (MGBG; NSC 32946), a competitive inhibitor of S-adenosyl-L-methionine decarboxylase (EC 4.1.1.50), currently being reevaluated for its clinical antileukemic activity. MGBG labeled with 14C in the guanylhydrazone moiety was administered i.v. (150 microCi; specific activity, 1.9 microCi/mumol; 20 mg total) to six patients with leukemia. All patients in the study had normal renal and hepatic function. [14C]MGBG underwent no in vivo metabolism; it disappeared from the plasma with an average terminal t 1/2 of 4.1 hr. The 72-hr cumulative urinary excretion was only 14.5 +/- 2.2% (S.E.M.) of the total radioactive dose. The apparent volume of distribution was 661 ml/kg and the total clearance rate was 21.2 ml/kg/min. The low urinary excretion rate and the relatively rapid plasma clearance suggest that MGBG may be sequestered in the body. Therefore, if MGBG is administered by a frequent treatment schedule, the prolonged biological half-life in humans may significantly contribute to its clinical toxicity.

Drug Evaluation↗
PubMed1981

Combination therapy with ticarcillin and sulfamethoxazole-trimethoprim for infections in patients with cancer.

Intravenous (IV) antibiotic therapy with a combination of ticarcillin disodium and sulfamethoxazole-trimethoprim was administered as initial empiric treatment of 218 febrile episodes in patients with cancer. Seventy-nine (77%) of 102 episodes of infection were cured, and the temperature returned to normal in 88 (74%) of 199 febrile episodes without proved infection. The response rates for the major sites of infection were as follows: septicemia, 89%; pneumonia, 52%, soft-tissue infections, 85%; and urinary tract infections, 100%. The cure rate of Gram-negative aerobic bacillary infections was 87%. No significant influence of initial neutrophil count on response rate was noted, although patients in whom the neutrophil count increased during therapy had a higher response rate (84%) than patients in whom the neutrophil count decreased or remained stable (72%). The combination of ticarcillin and IV sulfamethoxazole-trimethoprim is satisfactory initial empiric antibiotic therapy for febrile episodes in neutropenic patients with cancer.

Bacterial Infections↗
PubMed1981

The development of the retinotectal projections from compound eyes in Xenopus.

The retinotectal projections from double-nasal (NN), double-temporal (TT) and double-ventral (VV) compound eyes in Xenopus were studied autoradiographically and electrophysiologically during development. Early TT projections were confined to rostrolateral tectum and spread with advancing age to cover most of the tectum by shortly after metamorphosis. Early VV projections showed a decreased density of label on lateral tectum. Early NN projections appeared to extend across the entire rostrocaudal length of the available tectum at all stages of development, but showed a decrease in label density on rostral tectum. The results are discussed in relation to various hypotheses about the formation of retinotectal connexions.

Animals↗
PubMed1980

Radiation exposure as a possible etiologic factor in hairy cell leukemia (leukemic reticuloendotheliosis).

The frequency of prior occupational, accidental, or therapeutic radiation exposure was significantly higher for hairy cell leukemia patients than for a control group of solid tumor patients (8/23 vs. 4/56, P < 0.01). Hairy cell leukemia patients were also more frequently involved in occupations at high risk of radiation exposure such as chemist, engineer, physicist, and health care facility worker (7/23 vs. 4/56, P < 0.01). The observation that the incidence of thyroid disorders among hairy cell leukemia patients was also unusually high (5/23 vs. 2/56, P < 0.05) was interpreted as further indirect evidence of excessive radiation exposure. It appears that radiation exposure may be an important contribution factor in the development of some case of hairy cell leukemia.

Adult↗
PubMed1980

Diagnosis of leukemia or lymphoma in the central nervous system by beta 2-microglobulin determination.

To detect early relapse in the central nervous systems (CNS) of patients with acute leukemia or lymphoma, we measured levels of beta 2-microglobulin (beta 2 m) in serum and cerebrospinal fluid (CSF). CSF levels were significantly higher in patients with leukemia (P < 0.001) or lymphoma (P < 0.02) with clinical evidence of CNS involvement than in those without this complication. When serum and CSF levels were measured simultaneously, the CSF level of beta 2 m was significantly higher than the serum level in patients with acute leukemia and lymphoma with CNS involvement (P = 0.05), but not in patients without CNS involvement. Serial determination of CSF beta 2 m correlated well with the clinical appearance and disappearance of CNS involvement. These data suggest that serial and simultaneous determination of beta 2 m in serum and CSF may be useful in early diagnosis of CNS involvement and in monitoring intrathecal therapy in patients with acute leukemia or lymphoma.

Acute Disease↗
PubMed1980

Factors related to length of complete remission in adult acute leukemia.

Two hundred and two adult patients with acute leukemia were analyzed to determine pretreatment and treatment factors that could predict for duration of bone marrow remission. Several factors had a significant effect on remission duration, including morphologic diagnosis (AML greater than ALL greater than AUL), initial blast cell count, age, serum LDH, fibrinogen level, labeling index, and in vitro agar colony growth. Patients who attained a remission quickly or in whom leukemic cells in blood and bone marrow were rapidly cleared had long remissions. After applying regression model fitting methods, the six major factors, in order of significance, were the initial serum LDH level, pretreatment fibrinogen level, the number of courses of treatment to obtain a remission, morphologic diagnosis, the halving rate of leukemic cells in the blood, and the age of the patient. The model derived from this study was applied to the 202 patients and suggested that patients likely to have short or long bone marrow remission can be identified.

Adolescent↗
PubMed1980

Superficial head and neck metastases in adults with widespread cancer.

In this study of 1,782 adult patients with disseminated malignancies, superficial soft tissue cervicocephalic metastases developed in about 1 in 20. In only six patients was the primary tumor located in the head or neck, and in one of these did it involve the skin or oral mucosa. In each instance the intraoral or extraoral soft tissue metastases were clearly apparent on physical examination. Biopsy should be performed on every newly formed persistent mucocutaneous lump or bump in the head and neck to rule out not only local tumor but metastasis from remote primary lesions.

Carcinoma↗
PubMed1980

4'-(9-Acridinylamino) methanesulfon-m-anisidide (AMSA): a new drug effective in the treatment of adult acute leukemia.

Sixty-two adults with previously treated acute leukemia were treated with 4'-(9-acridinylamino) methanesulfon-m-anisidide (AMSA) with a total dose of 150 mg to 1320 mg/m2 of body surface area given over 3 to 14 days intravenously. Of the 56 patients who received an adequate trial, 13 achieved a complete remission and six had a partial remission. The best therapeutic results were observed when AMSA was used at a dose level of 75 to 90 mg/m2 per day for 7 days, which resulted in nine complete remissions among 30 patients. Eleven of 38 patients with myeloblastic leukemia achieved complete remission, and three of 13 with lymphoblastic disease achieved partial remission. Complete remissions were observed in nine of 39 patients who were refractory to cytarabine and anthracyclines, indicating a lack of cross-resistance between these drugs and AMSA. The median duration of remission was 12 weeks, and the median survival of responders was 28.5 weeks. The major toxicity of AMSA therapy was severe myelosuppression resulting in frequent infections during induction therapy. Our results indicate that AMSA has significant activity against refractory adult acute leukemia and deserves further evaluation.

Adolescent↗
PubMed1980

Quantitation of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate in the leukemic cells from bone marrow and peripheral blood of patients receiving 1-beta-D-arabinofuranosylcytosine therapy.

A method for the detection and quantitation of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate (ara-CTP), the active metabolite cells and leukemic cells of the peripheral blood from patients receiving ara-C therapy is described. ara-CTP is separated from normal cellular nucleotides by high-pressure liquid chromatography and is quantitated by its absorbance of ultraviolet light at 280 nm with a lower limit of sensitivity of 25 pmol/2 x 10(7) cell equivalents. During separate courses of continuous infusion of different therapeutic doses of ara-C, ara-CTP accumulated in the leukemic bone marrow cells of a patient with acute myelogenous leukemia in proportion to the dose of ara-C. Continuous infusion of ara-C (90 mg/sq m/day) resulted in plateau levels of ara-CPT in peripheral blast cells after 24 hr (115 pmol/1 x 10(7) cell equivalents). A priming dose of ara-C(125 to 250 mg/sq m) followed by a 1-hr infusion of an equal dose of ara-C to patients with acute myelogenous leukemia facilitated the determination of ara-CTP retention in bone marrow and peripheral blood leukemic cells in vivo. This procedure should be useful for extended studies of the biochemical pharmacology of ara-CTP in vivo.

Arabinofuranosylcytosine Triphosphate↗
PubMed1980

Knowledge acquisition from historical data: application to breast cancer patients.

The thesis of this paper is that knowledge acquired from historical data collected in a clinical research program may be used for planning future clinical trials and evaluating the effect of treatment. In a breast cancer study comparing adjuvant, treatment with FAC-BCG to control treatment Cox's regression model including number of involved nodes, stage of disease, and menopausal status was used to demonstrate that FAC-BCG patients have superior disease-free survival. A logistic regression model for acute leukemia involving age, cytogenetics, prior hematologic abnormality, temperature, serum creatinine, and hemoglobin was obtained by fitting to 325 previously untreated adult patients who received treatment between March, 1973 and April, 1977. The model was validated by prospective application to 107 patients treated between May, 1977 and December, 1978. Results in this trial will be compared with those in similar patients for the historical control series.

Acute Disease↗
PubMed1980

The retinotectal projections from surgically rounded-up half-eyes in Xenopus.

In Xenopus embryos of stage 32 half of one eye anlage was removed and the remaining half was surgically rounded-up. The visuotectal projections through such half-eyes, recorded after metamorphosis, showed in most cases a deformation of the map which corresponded to the deformation imposed on the half-eye at operation. Some eyes gave normal maps and some showed mirror-reduplication.

Animals↗
PubMed1979

Treatment of acute leukemia in protected environment units.

Thirty evaluable patients with acute leukemia (AL), aged 14 to 48-year-old received remission induction chemotherapy on a protected environment-prophylactic antibiotic program. Twenty-seven (90%) of these patients achieved complete remission and 17 remained in complete remission for 1 to 22 months. Although these patients spent 36% of their time with neutrophil counts less than 100/mm3, they spent only 20% of their time with fever. Major infection was present during only 7% of the days when neutrophil count was less than 100/mm3. No patient died of an infectious complication during remission induction therapy.

Adolescent↗