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Biomedical subjects

M J Keating

Publications and source records attributed to M J Keating.

At least 379 records · Page 21Linked to original sources
PubMed1979

A randomized comparative trial of three aminoglycosides--comparison of continuous infusions of gentamicin, amikacin and sisomicin combined with carbenicillin in the treatment of infections in neutropenic patients with malignancies.

Continuous infusions of gentamicin, amikacin or sisomicin combined with carbenicillin were compared in a randomized study in the treatment of 572 febrile episodes in 281 patients with cancer. The three treatments (C+A, C+A and C+S) were equally effective with no significant differences in response rate overall (67%, 68%, 67%) or in any infection, except septicemia where C+G had a significantly lower response rate than the other two groups. Pneumonia, the most common infection, had the lowest response rate for all three groups (45-50%). Klebsiella spp. were the most common pathogens and showed a lower response rate than other gram-negative bacilli (P = 0.003). Patients with persistent severe neutropenia had a response rate of 56%. Azotemia was significantly less common in patients with documented infection treated with C+A than in the C+S group. Combinations of carbenicillin plus an aminoglycoside antibiotic are effective for the treatment of infections in neutropenic patients.

Adolescent↗
PubMed1979

Clinical studies with rubidazone.

One hundred and thirty-three patients, 94 with acute luekemia and 39 with solid tumors, received rubidazone, alone or in combination, at M. D. Anderson Hospital. The initial study, a phase I--II study carried out in 39 patients with acute leukemia, revealed substantial antileukemic activity with optimal results at a dose level of 450 mg/m2. Toxic manifestations included an acute reaction suggestive of histamine release with dose-limiting mucositis at a dose of 600 mg/m2. Forty-seven patients with acute leukemia were treated at phase II dose levels. Thirteen of 32 patients (42%) with acute myelogenous leukemia and seven of ten patients (70%) with acute lymphocytic leukemia achieved complete remission. Twenty-seven previously untreated patients with acute leukemia who were greater than 50 years old were treated with rubidazone in combination with cytosine arabinoside, vincristine, and prednisone. Fifteen patients (50%) achieved complete remission including 12 of 15 patients (73%) who were treated at a dose of 200 mg/m2 of rubidazone on Day 1 and a dose of 70 mg/m2/day X 7 days of cytosine arabinoside (continuous infusion). For patients with solid tumors, the dose-limiting toxic effect was myelosuppression at a dose of 200 mg/m2. Other toxicity at that dose level was minimal. The best responses were seen in patients with carcinoma of the period with two of four evaluable patients showing objective tumor regression. Of six previously untreated patients with thyroid carcinoma none responded, and in a phase II study of patients with breast cancer there were no partial remissions among 13 patients. Cardiac toxicity, manifested by congestive heart failure, occurred in seven patients at cumulative doses of 1050--2600 mg/m2 of rubidazone; all patients had had prior anthracycline therapy at low doses. Rubidazone has been shown to be an active antileukemic agent, but appears to be less active than Adriamycin in our studies of patients with solid tumors.

Acute Disease↗
PubMed1979

Phase I-II study of piperazinedione in adults with solid tumors and acute leukemia.

Piperazinedione was administered to 79 patients with solid tumors on an intermittent schedule with single doses of 1.5-36 mg/m2. Courses were usually repeated at 4-week intervals. Twenty-five patients with leukemia were treated at doses of 18-36 mg/m2 (occasionally for 2 successive days) every 1-4 weeks. Of 48 evaluable patients with malignant melanoma, three (6%) achieved partial remission and nine (20%) had stable disease. Eight of 17 (47%) patients with adenocarcinomas and one of two (50%) patients with lymphomas also had stable disease. Six of 14 (43%) patients with acute myelogenous leukemia showed hematologic improvement, as did one of 11 (9%) patients with blast cell crisis of chronic myelogenous leukemia. The principal toxic effect was myelosuppression, which occurred in 69% of the patients with solid tumors. Profound bone marrow aplasia occurred in 19% of the patients, resulting in six deaths (8%). Risk factors for marrow aplasia included extensive prior therapy, prior nitrosoureas, cumulative toxicity from piperazinedione, and abnormal liver function tests. The recommended doses for further studies are 9 mg/m2 for patients with risk factors for marrow aplasia, 12 mg/m2 for patients with prior therapy, 15 mg/m2 for previously untreated patients, and 24-36 mg/m2 for patients with acute leukemia.

Adult↗
PubMed1979

The relationship between retinal and tectal growth in larval Xenopus: implications for the development of the retino-tectal projection.

The modes of retinal and tectal histogenesis, as well as the patterns of terminal distribution of optic axons in larval Xenopus were studied, using anatomical techniques. We show that the retina grows by adding strips of cells at its ciliary margin. The pattern of retinal growth is asymmetrical along the dorso-ventral axis of the retina. On the other hand, the tectum grows by adding newly formed cells caudo-medially. The most rapid tectal growth takes place between stages 50 and 53, and thereafter only a small proportion of cells are added near the midline of the caudal tectum. Despite such incongruent modes of retinal and tectal growth, retinotopic order is maintained throughout larval life. We present here further evidence supporting the idea that connexions between the arrays of retinal and tectal cells shift progressively caudo-medially on the tectum during the period of growth. When the temporal pole of the retina is destroyed at various developmental stages, the density of degenerating synapses is always highest in the rostral pole of the tectum. Moreover, optic terminals stemming from the central retina spread caudally, invading newly maturing regions of the tectum. Quantitative analysis of the terminal distributions of optic axons suggest that orderly shifts in synaptic contacts between optic axons and tectal dendrites take place in the course of development. Ultrastructural observations on the maturing tectal neuropil are consistent with this view.

Animals↗
PubMed1978

Randomized trial of protected environment--prophylactic antibiotics in 145 adults with acute leukemia.

One hundred and forty-five adults with acute leukemia were randomized to receive remission induction therapy in or out of a protected environment (PE) with prophylactic antibiotics orally (PA) or systemically (SA). Sixty-three patients were randomized in PE and 82 outside a PE. The proportion of patients who survived long enough to receive an adequate trial was higher in the PE (97%) than out (82%) (P = .01). The complete remission (CR) rate was 71% in and 43% out of the PE (P less than .01). Fifty-five patients received PA and 90 received SA. The CR rates were 61% and 45%, respectively. Of the 145 patients, 73 (50%) developed 102 episodes of major infections. Twenty-six of 63 patients in the PE developed major infection compared to 47 of 82 outside a PE (P = .08). The incidence rate of 13% fatal infections in a PE was significantly smaller than the 28% rate outside a PE (P = .04). The number of days with infections at less than 500 neutrophils/mm3 was also significantly lower inside a PE than outside (P less than .01). When comparing patients receiving SA or PA, there was no statistically significant difference in the incidence of infections. Forty-one patients received OAP Chemotherapy and 104 received adriamycin-OAP plus BCG. The CR rate on OAP was 44% compared with 60% on Ad-OAP + BCG. Infection rates were 76% and 40%, respectively (P less than .01). The median survival time was 72 weeks for patients in PE compared with 42 weeks for patients outside a PE (P less than .01). The prophylactic antibiotic regimens were well tolerated by most patients. This prospective randomized study has demonstrated statistically significant advantages for a lowered risk of fatal infection, higher CR rate and longer survival of patients treated in a PE with prophylactic antibiotics compared with patients treated in a conventional hospital room. Also, there was evidence for the superiority of adriamycin-OAP + BCG treatment compared with OAP.

Acute Disease↗
PubMed1978

Isophosphamide therapy for hematologic malignancies in patients refractory to prior treatment.

Isophosphamide was administered to 27 patients with acute leukemia and to 15 patients with malignant lymphoma refractory to primary therapy. The starting dose of isophosphamide was 1200 mg/m2 administered as a daily continuous infusion x 5 days; the courses of treatment were repeated every 2-3 weeks. Of the 27 patients with acute leukemia, four achieved complete remission, two achieved partial remission, and two achieved hematologic improvement. However, no responses occurred in ten patients with acute myelogenous leukemia (AML). Thus, the response rate was 47% (eight responses among among 17 patients, in patients with acute lymphoblastic leukemia and acute undifferentiated leukemia. Seven of the 15 patients with malignant lymphoma responded. Most responses (five of six patients) occurred in patients with diffuse histiocytic lymphoma. Twenty-one of the 42 patients had received prior therapy with cyclophosphamide and 12 of these patients (two with leukemia and ten with lymphoma) responded, thus suggesting that as in the treatment of L1210 leukemia, isophosphamide is effective for tumors resistant to prior cyclophosphamide therapy. No significant genitourinary toxicity occurred; however, myelosuppression became the dose-limiting toxicity. Isophosphamide is active in malignant lymphomas and acute leukemias (except AML) and may have a role in combination regimens for such diseases.

Acute Disease↗
PubMed1977

Hypocalcemia with hypoparathyroidism and renal tubular dysfunction associated with aminoglycoside therapy.

Seventeen patients with malignant disease developed a complex metabolic syndrome of 2-8 weeks' duration characterized by hypocalcemia, hypomagnesemia and hypokalemia following administration of the aminoglycoside group of antibiotics. Gentamicin, Tobramycin, Amikacin, and Sisomicin were all involved. Other features noted were hypoalbuminemia, hypophosphatemia, and hypouricemia. Low immunoreactive parathyroid hormone (i-PTH) levels in the presence of hypocalcemia and absence of hyperplastic changes in the parathyroid gland examined at postmortem confirmed a diagnosis of hypoparathyroidism. Immunoreactive calcitonin levels (i-CT) were not elevated. Renal tubular wasting of potassium and magnesium was documented in six patients and excessive urinary loss of sodium, phosphate, and uric acid was noticed. Twelve patients died before recovering from the metabolic stress and five patients developed progressive renal impairment. A possible potentiating action of chemotherapeutic agents, especially Adriamycin, is suggested.

Adult↗