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Biomedical subjects

M J Keating

Publications and source records attributed to M J Keating.

At least 307 records · Page 17Linked to original sources
PubMed1986

Visual deprivation and the maturation of the retinotectal projection in Xenopus laevis.

There has been a resurgence of interest, recently, in the possible role of neural activity in the ordering of synaptic connections in the lower vertebrate retinotectal system. Blockade of all neural activity, by chronic administration of tetrodotoxin (TTX), during the regeneration of the optic nerve in goldfish has been found to prevent the re-emergence of a fully ordered retinotectal projection. We sought to determine the effects of visual deprivation, a less radical perturbation of neural activity than that produced by TTX, on the initial development of the retinotectal projection. The contralateral visuotectal projection was studied in Xenopus laevis which had been reared in darkness from before the onset of visual function. The projection mapped electrophysiologically at metamorphic climax, or in postmetamorphic juveniles, showed a normal retinotopic topography. The topographic precision of the projection, as revealed by the multiunit receptive field sizes, was the same in light- and dark-reared animals. The laminar distribution, in the superficial neuropil of the optic tectum, of terminals from different classes of retinal ganglion cells was also normal. It is concluded that the specific retinotectal connections underlying these features of the projection are generated by intrinsic developmental processes which do not require visual experience. Among these intrinsic processes might be 'spontaneous' neural activity.

Animals↗
PubMed1986

PMMA lenses worn for twenty years.

In this study of 150 eyes (75 patients) wearing PMMA lenses for at least twenty years, most patients experienced only small change in corneal curvature. Some developed with-the-rule astigmatism, but 27% showed no variations in corneal toricity, although a refractive change of +/- 3.00 D was observed. 40 eyes had no difference of cylinder Rx and 13 maintained the same spherical correction. Graphs indicate a limited spread of statistically significant changes in the corneal curvature. Complete information on corneal integrity is not included in this study but biomicroscopic examination did not disclose any serious adverse conditions in the opinion of the authors.

Adolescent↗
PubMed1986

Ocular migration and the metamorphic and postmetamorphic maturation of the retinotectal system in Xenopus laevis: an autoradiographic and morphometric study.

The growth of the retina and tectum during larval life in Xenopus has previously been studied extensively. These two structures continue to grow in metamorphosing and postmetamorphic animals. During these later stages there are marked changes in eye position. We have used histogenetic and morphometric techniques to monitor retinal and tectal growth in Xenopus aged from stage 58 of larval life to ten years postmetamorphosis. The relative eye migration was quantified with optical techniques. An attempt has been made to relate modes of retinal growth to problems associated with changing interocular geometry. The predominant mode of growth during this period is hypertrophic, that is, it is due largely to an increase in size and complexity of existing elements, rather than the histogenetic creation of new elements. In the retina, however, tritiated thymidine autoradiography reveals that histogenesis does persist until at least six months after metamorphosis. The rate of histogenesis is much decreased compared with that of larval stages but, like that of larval stages, it takes place at the ciliary margin. It is asymmetrically distributed in the retina, most histogenesis occurring at the ventral retinal pole and very little at the dorsal retinal pole. Some histogenesis occurs at the nasal and temporal retinal poles. Thymidine autoradiography and cell counts indicated that little significant histogenesis occurs in the tectum after metamorphic climax. Two possible biological reasons for the asymmetry of retinal histogenesis have been examined. The first was the suggestion that the asymmetry was related to the emergence, during this period, of a binocular visual field secondary to the relative migration of the two eyes. It is shown that the asymmetric pattern of histogenesis is not closely related to those retinal areas that come to view binocular visual space. It was found, however, that the asymmetry of retinal growth from metamorphic climax was that required to stabilize retinal visual field positions with respect to body position. It is suggested that this minimizes the requirements for visuomotor readjustments that would otherwise be necessary to compensate for a situation in which eye position, relative to the body, is changing.

Age Factors↗
PubMed1985

Subacute pulmonary failure complicating therapy with high-dose Ara-C in acute leukemia.

Seventy-four adult patients with acute leukemia in relapse were studied. They received high-dose intravenous boluses of cytosine arabinoside (Ara-C) according to the following schedules: 3 g/m2 over 2 hours, every 12 hours for 4 to 12 consecutive doses, or a continuous infusion over 5 days at 200, 400, or 800 mg/m2/day. The patients' ages ranged from 16 to 68 years (median, 35). Subacute pulmonary failure attributable to Ara-C was observed in 16 of 72 evaluable patients (22%) and appeared 2 to 21 days (median, 6) after the first dose. None of the 28 patients who received up to six doses experienced any toxicity. With repeated courses or more than six doses in the first course there was a sharp increase in the incidence of toxicity. Thus, subacute pulmonary failure developed in 6 of 24 patients who received 9 doses and 6 of 19 patients who received 12 doses. The increase in toxicity with increasing number of doses is significant (P = 0.03). This suggests that the high-dose Ara-C regimen should be used with awareness of possible drug-induced pulmonary toxicity.

Acute Disease↗
PubMed1985

A species difference between Rana and Xenopus in the occurrence of intertectal neuronal plasticity.

In anuran amphibians, a system of neuronal connections links the two optic tecta and is involved in projections of the binocular visual field to the optic tecta. Electrophysiological studies have shown that in the frog, Xenopus laevis, the pattern of connections may be modified by procedures such as larval rotation of one eye. This modification appears to be effected by visual experience. Workers in other laboratories, however, found no evidence of such a modification in the related frog Rana pipiens. This difference in results may have been due to different rearing conditions and different recording techniques or may reflect a true species difference, in this respect, between Rana and Xenopus. In the present experiments, an attempt was made to distinguish between these possibilities by performing eye rotations in Rana and Xenopus, rearing them as identically as possible and recording from them under identical conditions. It was found that while Xenopus displayed the modification of intertectal connections, Rana did not. It is concluded that the different responses of the intertectal systems to larval eye rotation in Xenopus and Rana reflect a species difference.

Adaptation, Physiological↗
PubMed1985

Remission from central nervous system involvement in adults with acute leukemia. Effect of intensive therapy and prognostic factors.

Eighty-seven adult patients who had achieved bone marrow remission of leukemia developed one or more episodes of meningeal leukemia. Multiple patient characteristics were examined for their effect on probability of achieving complete remission from meningeal disease and for their effect on duration of meningeal remission. Presence of obtundation (P less than 0.01) or other symptoms of meningeal disease (P = 0.02) were associated with a low remission induction rate. Other factors which tended (P = 0.06-0.20) to be associated with low remission induction rates included high cerebrospinal fluid (CSF) opening pressure, absence of splenomegaly at initial diagnosis, high peripheral blood leukocyte count (WBC) at the episode of marrow disease most recently preceding the meningeal disease, and use of only one as opposed to two or more intrathecal drugs as treatment. Factors associated with long duration of meningeal remissions included diagnosis (AML greater than acute undifferentiated leukemia greater than ALL, P = 0.05), absence of symptoms (P = 0.04), low CSF WBC (P = 0.01), rapid attainment of meningeal remission (P = 0.01), rapid attainment of initial bone marrow remission (P = 0.02), and long duration of initial bone marrow remission (P less than 0.01). Absence of cranial or peripheral neuropathies, low CSF protein and opening pressure, and short time interval between diagnosis of marrow and meningeal disease also tended (P = 0.06-0.20) to be associated with long meningeal remissions. Patients treated according to an intensive protocol utilizing cranial irradiation and triple drug treatment via an Ommaya reservoir had substantially longer meningeal remissions than did patients treated with less intensive therapy (P = 0.01). Relapse-free survival curves suggest that some patients are cured of their meningeal disease.

Acute Disease↗
PubMed1985

Phase I evaluation of intravenous difluoromethylornithine--a polyamine inhibitor.

Difluoromethylornithine (DFMO), a non-competitive inhibitor of ornithine decarboxylase (ODC), the rate limiting enzyme of the polyamine synthetic pathway was evaluated in a Phase I trial. Intravenous DFMO was given to twenty patients with refractory leukemia by continuous infusion in doses from 5.5 to 64 g/m2. Toxicity clearly attributable to the drug was not severe and other than nausea and vomiting did not increase with dose. The previously reported ototoxicity which occurred with the oral form appeared to be less frequent. Loss of hearing which improved when the drug was stopped was seen in four patients, three of whom were simultaneously receiving aminoglycosides. Anorexia occurred in some patients at all doses. Vomiting, necessitating dosage reduction, was a significant problem at the highest dose administered. No patient achieved a remission but there was stabilization or decrease in circulating blast cells in several patients. This growth inhibition did not appear to be dosage related.

Acute Disease↗
PubMed1985

Prospective randomized trial of antibiotic prophylaxis in acute leukemia.

Patients undergoing initial remission induction chemotherapy for acute leukemia in a protected environment unit were randomly assigned to parenteral antibiotic prophylaxis or oral and parenteral antibiotic prophylaxis. Complete remissions were obtained in 82 percent of the 45 patients receiving oral and parenteral antibiotic prophylaxis and 76 percent of the 41 patients receiving parenteral antibiotic prophylaxis. Approximately 20 percent of the patients in both groups have had a continuous complete remission for more than five years. The episodes of fever of unknown origin and major infection were significantly more common in patients receiving parenteral antibiotic prophylaxis, although the episodes of local infection were similar in both groups. The duration of remission and survival was similar in both groups. Hence, the oral and parenteral antibiotic regimen was more effective for infection prophylaxis, but had no effect on response to antileukemic chemotherapy.

Acute Disease↗
PubMed1985

Orofacial aspergillosis in acute leukemia.

The clinicopathologic characteristics of orofacial aspergillosis in thirteen hospitalized patients who developed the infection while receiving chemotherapy for acute leukemia are described. Clinically, the primary sites of infection, in decreasing order of frequency, were the paranasal sinuses, nasal cavity, mouth, and facial skin; the corresponding order for the secondary sites was orbit, nasal cavity, facial skin, and mouth. Pathologically, the fungal lesions in the nasal, oral and sinusoidal cavities were black, ulcerated, and escharotic due as a direct result of tissue destruction by the organism and an indirect result of thrombotic vascular infarction. The orbital lesions were deep red, granulomatous, and productive of proptosis and ectropion. Seven of the thirteen patients had concomitant pulmonary aspergillosis. The orofacial infections were not responsive to antifungal therapy in the absence of remission of the leukemia and restoration of depressed host defenses. In two patients who did achieve remission, the aspergillosis was controlled by the intravenous administration of amphotericin B.

Acute Disease↗
PubMed1985

Intertectal neuronal plasticity in Xenopus laevis: persistence despite catecholamine depletion.

In normal Xenopus, the tectum receives a direct projection from the contralateral retina and an indirect projection, via the intertectal system, from the ipsilateral eye. The two maps of binocular visual space, at each tectum, are in register. If one eye is rotated during larval development, the ipsilateral visuotectal projection compensates by changing its orientation. Rearrangement of the intertectal system brings the ipsilateral map back into register with the contralateral map. We sought to determine whether this intertectal plasticity required normal levels of brain monoamines. Animals received an eye rotation between stages 55-63 of larval life and were then placed in one of 3 groups. A first control group received no further treatment. A second control group was given intraventricular injections of ascorbate vehicle. The experimental group was given intraventricular injections of 6-hydroxydopamine in ascorbate vehicle. Two to 3 months after metamorphosis, visuotectal projections were mapped electrophysiologically and the brains were assayed for monoamines. Intertectal plasticity occurred in all 3 groups of animals, including animals in which brain catecholamine levels were severely reduced. We conclude that normal levels of brain catecholamines are not required for this form of neural plasticity.

Animals↗
PubMed1985

Loss of the Y chromosome in acute myelogenous leukemia: a report of 13 patients.

Thirteen male patients with acute myelogenous leukemia who, on bone marrow chromosome analysis, were missing all or part of the Y chromosome were treated at this institution between 1975 and 1983. Giemsa-banding techniques were performed in 12 cases. Twelve showed -Y in at least 80% of bone marrow metaphases, and one patient had 25% 46,XYqh-. The loss of the Y chromosome was the sole karyotypic abnormality in nine patients, and the remaining four had additional chromosome changes. The peripheral blood lymphocytes were diploid in all except three cases, where no mitotic cells were recovered. The median age was 55 years, eight patients had acute myelogenous leukemia (M2) and five acute myelomonocytic leukemia (M4). Six patients (46%) had an antecedent hematologic disorder. Eleven patients received standard induction combination chemotherapy. Complete remission was achieved in seven patients (63%). Remission bone marrow chromosome analysis showed 100% 46,XY in all seven cases. The median durations of complete remission and survival were 10 months and 12 months, respectively. The review suggests that -Y is a consistent, although uncommon, chromosome marker in acute myelogenous leukemia, associated with an aggressive clinical course and intermediate prognosis.

Adolescent↗
PubMed1985

Suppression of clonal evolution in two chronic myelogenous leukaemia patients treated with leucocyte interferon.

Two patients with Philadelphia chromosome-positive (Ph1+) chronic myelogenous leukaemia (CML) were treated with human leucocyte interferon (HuIFN-alpha). Karyotypic changes in addition to the Ph1 chromosome developed in these patients before the start of HuIFN-alpha treatment. In one patient the administration of HuIFN-alpha resulted in clinical haematological remission and stable suppression of the secondary Ph1 clone. The second patient was in myeloid blastic crisis when given HuIFN-alpha. While she was receiving HuIFN-alpha, suppression of the blast cell population in the bone marrow occurred. The subsequent cytogenetic changes included a near-complete suppression of a secondary Ph 1 clone of cells carrying a deletion in the short arm of chromosome 7 and partial population of the bone marrow with primary Ph1 clone. These observations suggest a potential role for interferons in altering the progressive course of CML.

Adult↗
PubMed1985

Acoustic vibration of the amphibian eardrum studied by white noise analysis and holographic interferometry.

The motion of the amphibian eardrum under free-field acoustic stimulation was investigated using time-averaged holography. We show that the amplitude is linearly related to sound pressure up to +/- 1000 nm. The frequency response of the eardrum shows broad resonance characteristics with a main peak between 1200-2200 Hz. The velocity of the tympanic membrane's motion at its resonance frequency matches the acoustic velocity of air particles. The resonance characteristics of the eardrum are also revealed by white noise stimulation. The power spectrum obtained by Fourier transformation of the autocorrelation of the response to noise resembles closely that obtained by holography.

Acoustic Stimulation↗
PubMed1985

Pretreatment of cytokinetics in acute myelogenous leukemia. Age-related prognostic implications.

To determine the clinical and biologic relevance of cellular kinetics in leukemia, DNA flow cytometric analysis was performed on bone marrow biopsy specimens from 148 previously untreated adult patients with acute myelogenous leukemia. The proportion of cells in synthesis, second growth, and mitosis (S + G2M) ranged from 4% to 33% with a median of 14%. The overall incidence of complete remission was not affected by the pretreatment cell cycle distribution. As in earlier studies, there was a marked decline in remission rate with advancing age from 73% for patients age less than or equal to 50 yr to 50% for those greater than 50 (P less than 0.01). Although not affecting remission induction overall, an increasing proportion of cells in S + G2M phase was favorable in patients under the age of 50 yr, but was associated with a progressive decline in remission rate in older patients (P = 0.01). This age-related divergent effect of cell cycle kinetics on initial response to therapy was confined to the less favorable subgroup of patients with karyotypic abnormalities, whereas patients with normal diploid cytogenetics had a consistently higher response rate regardless of proliferative activity. A positive correlation was also observed between percent of S + G2M cells and the proportion of diploid metaphases in young patients, contrasting with a negative correlation in the older age group. Our observations strongly suggest that the well-recognized prognostic effect of age on remission induction is not entirely host-mediated, but is at least partly an expression of disease-intrinsic differences between young and older patients.

Adult↗
PubMed1985

Intensive combination chemotherapy (ROAP 10) and splenectomy in the management of chronic myelogenous leukemia.

To investigate the role of intensive chemotherapy in chronic myelogenous leukemia (CML), we treated 37 patients who had Philadelphia-positive benign-phase disease with rubidazone 300 mg/m2/d 1 (or daunorubicin 30 mg/m2/d X 4), cytosine arabinoside 80 mg/m2/d X 10, vincristine 2 mg/d 1, and prednisone 100 mg/d X 5 (ROAP 10), every four weeks for a median of three cycles. This treatment was followed by splenectomy and by subsequent maintenance therapy with 1 to 5 g hydroxyurea daily in intermittent courses. After a median follow-up of 42 months (range, 24 to 54 months), 20 patients (54%) remain in benign phase. The projected median survival is 52 months, and the three-year survival rate is 67%. Six patients (16%) developed blastic crisis, and eight died in the benign phase. A significant cytogenetic response, defined as a fall in the percentage of Philadelphia-positive cells to less than or equal to 30%, occurred in 18 (53%) of 34 patients who had serial cytogenetic studies. Six patients (18%) had reductions to 35% to 90%, whereas ten remained 100% positive. Cytogenetic response lasted for a median of six months from the time of maximal response (range, 1 to 18 months). Blastic crisis or accelerated disease developed in seven (44%) of the 16 patients who manifested minimal or no cytogenetic response, compared to only two of the 18 patients (11%) who achieved a significant cytogenetic response. Toxicity, which resulted in one death, was due to myelosuppression and consisted of febrile episodes during neutropenia (24% of courses), documented infections (8% of courses), and bleeding (8% of courses). ROAP 10 intensive therapy produces moderate survival improvement for CML patients compared to a matched historical control group of patients treated at our institution, but it has considerable myelosuppressive toxicity. The Philadelphia chromosome response is an important treatment-related prognostic factor.

Adolescent↗
PubMed1985

A characteristic pattern of leukemic cell differentiation without cytoreduction during remission induction in acute promyelocytic leukemia.

While differentiation of leukemic cells in vitro is well established, the role of differentiation in vivo is not defined and is generally attributed to differentiation inducers. In five patients with acute promyelocytic leukemia (APL) an unusual pattern of a slow and progressive decrease of immature blasts with a concomitant increase in mature cellular elements was observed following intensive combination chemotherapy. All patients eventually achieved complete remission, four of them without an intermediate phase of marrow hypoplasia. This morphologic pattern of response suggests that leukemic cellular differentiation rather than cytotoxicity was one mechanism involved in remission induction. Cytogenetic studies of remission revealed disappearance of the cytogenetic marker, the balanced translocation between the long arms of chromosomes 15 and 17. This remission induction process appears to be due to the cellular biologic characteristic rather than the therapy used as it occurs in a substantial proportion of patients with APL. It should be considered for optimal diagnostic and therapeutic decisions.

Acute Disease↗
PubMed1985

A unique pattern of central nervous system leukemia in acute myelomonocytic leukemia associated with inv(16)(p13q22).

Twenty-six patients with inv(16)(p13q22) or del(16)(q22) in association with acute myelomonocytic leukemia (AMML-M4, FAB classification), and abnormal marrow eosinophils have been treated at this institute. Initial bone marrow eosinophilia (greater than or equal to 4%) was observed in 22 of 26 patients (85%), and abnormal eosinophil morphology, characterized by immature cells with some interspersed basophilic granules, was evident in 26 of 26 (100%). Giemsa-banded chromosome analysis performed in all patients revealed 16 cases with inv(16)(p13q22) alone, and ten cases with additional chromosome changes. Twenty-five patients received combination induction chemotherapy, and 23 (92%) achieved complete remission (CR). The median duration of remission was 18 months (range, six to 72 + months), and the median duration of survival was 34 months (range, 0.5 to 133 months). Nine patients (35%) relapsed in the CNS at a median time of 19 months (range, six to 133 months) from first marrow CR. All patients had leptomeningeal disease, and in addition, six of nine (66%) demonstrated two or more enhancing lesions on computed tomography brain scan, consistent with intracerebral myeloblastomas. Review of 384 Giemsa-banded patients with acute myeloid leukemia revealed no other morphologic or cytogenetic subgroup with either an equivalent incidence of CNS leukemia or documented intracerebral myeloblastomas. This series of inv(16)(p13q22)/del(16)(q22) AMML reports a favorable prognosis for such patients and associates a specific clonal cytogenetic subgroup of acute leukemia with a distinct propensity for CNS relapse, manifesting as leptomeningeal disease and intracerebral myeloblastomas.

Adult↗