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Biomedical subjects

M O'Leary

Publications and source records attributed to M O'Leary.

At least 55 records · Page 3Linked to original sources
PubMed1993

Neurochemical alterations in Rett syndrome.

The Rett syndrome (RS) is a neurological disorder associated with severe mental deficiency and neurological manifestations of cortical and extrapyramidal dysfunction. The present report is (1) a postmortem brain study that compares the levels of choline acetyltransferase (ChAT) activity and the binding density of selected neurotransmitter receptors in four cases of RS and five normal controls of similar age and (2) a study of cerebrospinal fluid (CSF) concentrations of the endogenous tridecapeptide neurotensin in 12 RS patients and 8 controls of similar age. The level of ChAT activity was lower in many cortical and subcortical regions in the RS brains as compared to control levels. The number of NMDA, AMPA, mu opioid and neurotensin binding sites, as well as CSF concentrations of neurotensin, did not differ significantly from control levels. The results suggest that changes in specific neurotransmitter systems, particularly cholinergic neurons, in the thalamus, cerebellum and basal ganglia may underlie the progressive deterioration in motor and cognitive function characteristic of this disorder.

Adolescent↗
PubMed1993

Synthetic prostaglandin E1 misoprostol as a treatment for tinnitus.

OBJECTIVE: A pilot study to determine if the synthetic prostaglandin E1 misoprostol is effective in treating severe tinnitus, to test the hypothesis that tinnitus production is related to prostaglandin metabolism. DESIGN: Blinded, placebo controlled, hemicrossover. SETTING: House Ear Clinic, Los Angeles, Calif. PATIENTS: A volunteer and convenience sample of 24 subjects complaining of severe tinnitus was recruited from mailings, telephone calls, and the clinic population. The patients were not preselected except to be in otherwise good health. INTERVENTION: Subjects were started on a regimen of placebo or 200 micrograms/d of misoprostol. The dosage was increased every 5 days by 200 micrograms until a total of 800 micrograms/d was achieved. After 1 month of drug administration, the placebo group was crossed over to the active drug phase. MAIN OUTCOME MEASURES: Outcome was measured in terms of subjective reports of tinnitus severity, sleep patterns, and ability to concentrate. RESULTS: Eight (33%) of the 24 patients reported improvement during the active drug phase. There were no placebo responders. Responders reported improvement in tinnitus severity, sleep, and concentration. CONCLUSIONS: Findings support the contention that prostaglandins may be useful in the treatment of tinnitus. Further studies with larger samples are needed before widespread use of this intervention can be recommended.

Adult↗
PubMed1993

Final height after treatment for childhood acute lymphoblastic leukemia: comparison of no cranial irradiation with 1800 and 2400 centigrays of cranial irradiation.

We analyzed growth and final heights in 127 patients (68 female patients) treated for childhood acute lymphoblastic leukemia. Central nervous system prophylaxis included either no cranial radiation therapy (CRT) (n = 38), irradiation with 1800 centigrays (cGy) (n = 36), or irradiation with 2400 cGy (n = 53). None of the patients received spinal irradiation. Mean (+/- SEM) age at diagnosis was 6.4 +/- 0.25 years, mean height standard deviation score (SDS) at diagnosis was 0.28 +/- 0.12, and mean age at final height was 18.26 +/- 0.19 years. The change in height SDS between diagnosis and achievement of final height was significant for all treatment groups: -0.49 +/- 0.14, no CRT; -0.65 +/- 0.15, 1800 cGy; and -1.38 +/- 0.16, 2400 cGy. Irradiated patients had a greater loss in height SDS compared with the nonirradiated patients (p < 0.01), and those treated with 2400 cGy CRT had a greater decrease in final height SDS than the patients treated with 1800 cGy (p < 0.01). Both younger age and female sex were significantly associated with a greater decrease in height SDS in the patients treated with CRT; girls < or = 4 years of age at diagnosis had a mean loss in height SDS that was more than twice that observed for others treated with the same dose of CRT. Thus, although modern regimens for acute lymphoblastic leukemia (no CRT or 1800 cGy CRT) appear overall to have only a modest impact on final height, patients, especially girls, treated with 1800 cGy CRT at a young age remain at risk for clinically significant growth failure.

Age Factors↗
PubMed1993

Auditory brainstem implant: II. Postsurgical issues and performance.

The auditory brainstem implant (ABI) restores some hearing sensations to patients deafened by bilateral acoustic tumors. Electrodes are stable for more than 10 years. In most cases nonauditory side effects can be avoided by judicious selection of the stimulating waveform and electrode configuration. Most perceptual measurements demonstrate that the ABI produces psychophysical and speech performance similar to that of single-channel cochlear implants. ABI patients receive suprasegmental information in speech and significant enhancement of speech understanding when the sound from the ABI is combined with lipreading.

Brain Stem↗
PubMed1991

Effects of interferon beta ser and transforming growth factor beta on prostatic cell lines.

The effect of interferon beta ser (IFN beta ser) on the growth of three prostatic cancer cell lines DU-145, PC-3 and LNCaP was studied. IFN beta ser inhibited growth of anchorage dependent semiconfluent monolayers and anchorage dependent colony formation of both DU-145 and PC-3 in a dose dependent manner but had no effect on LNCaP. Transforming growth factor beta (TGF beta 1) inhibited proliferation of DU-145 and PC-3 cells in 1% but not 8% fetal calf serum. The combination of TGF beta 1 and IFN beta ser was additive in its effects on growth. Neither epidermal growth factor (EGF) nor transforming growth factor alpha (TGF alpha) reduced the antiproliferative effect of IFN beta ser on these cells. These antiproliferative effects were reproduced in studies on primary epithelial cell cultures derived from prostate specimens with various pathologies. The potential use of IFN beta ser in combination with hormonal therapy to delay the development of hormone refractory tumors is discussed.

Cell Count↗
PubMed1990

Organ-specific modulation of gene expression in transgenic plants using antisense RNA.

We have shown leaf-specific inhibition GUS gene expression in transgenic Nicotiana plants using an antisense RNA with a 41-base homology spanning the translation start codon of the gene. GUS was expressed from the nominally constitutive 35S promoter and the antisense RNA was expressed from the light-regulated ca/b promoter of Arabidopsis thaliana. A range of GUS inhibition from 0 to 100% was obtained by screening a small population of transgenic plants and the specific levels of inhibition observed were stably inherited in two generations. An antiGUS 'gene' dosage effect was observed in plants which were homozygous for antiGUS. RNA detection results suggest that duplex formation with the 41 base pair antiGUS RNA destabilized the GUS mRNA and that an excess of antisense RNA was not required. Our results demonstrate the potential of antisense RNA as a strategy for obtaining plant mutants, especially 'down mutations' in essential genes where only a short 5' sequence of the mRNA is required. They also suggest that the 'position effect' on gene expression could be used in conjunction with an antisense RNA strategy to provide a versatile approach for crop improvement.

Base Sequence↗
PubMed1989

The effect of cyclosporine on the use of hospital resources for kidney transplantation.

Over the past decade the clinical results of kidney transplantation have improved substantially, with much of the benefit being attributed to the introduction in late 1983 of the immunosuppressive drug cyclosporine. To assess the effect of cyclosporine on the use of hospital services, we studied 702 patients who received kidney transplants at the University of California, San Francisco, between July 1982 and June 1986. All services were priced in constant 1985 dollars, and multiple regression analysis was used to adjust for changing patient and hospital characteristics. The introduction of cyclosporine for patients receiving kidneys from cadavers was associated with a significantly shorter adjusted mean postoperative stay (26.4 days as compared with 37.0 for patients not taking the drug; P less than 0.0001) and lower adjusted mean hospital charges ($28,649 as compared with $37,895; P less than 0.0001), although cyclosporine was not associated with changes in the use of services by patients who received transplants from living related donors. Cyclosporine was also associated with a reduction in the use of certain ancillary services, such as laboratory tests and radiographic procedures. In patients without diabetes who received cadaver kidneys, a sequential cyclosporine regimen (in which a combination of antilymphoblast globulin, prednisone, and azathioprine was given before cyclosporine) reduced the use of hospital services even more than did a cyclosporine regimen in which the combination was not given. The results suggest that new medications, such as cyclosporine, that reduce the frequency of complications and improve outcomes may also reduce the use of hospital resources.

Adult↗
PubMed1988

In vitro malignant transformation of in vivo ENU-induced rat ovarian Sertoli cell tumor (adenoma).

An N-ethyl-N-nitrosourea-induced rat ovarian Sertoli cell tumor was grown in tissue culture in Dulbecco's modified Eagle's medium (DMEM) supplemented with 25% horse serum (HS) and a hormone combination of 20 ng/ml each of hydrocortisone, insulin, and prolactin. This tissue culture derived from a nonsteroid hormone-producing tumor. Cytofluorometry and karyotyping of the nonhormone-producing tumor cell line (SCTL-1) revealed a diploid pattern for the early passage (P1), which became hyperdiploid (P10), and then aneuploid (P20). These cells had an epitheloid pattern, grew in a monolayer at early passages. After P10 the cells were transplanted into newborn rats and nude mice and resulted in high incidences of tumors (up to 100%). The cell line (SCTL-1) continued to grow in DMEM, 10% HS, and no hormone supplementation after P10. This study revealed that a benign rat ovarian Sertoli cell tumor after multiple passages in vitro underwent sequential genotypic and phenotypic changes and became highly malignant.

Adenoma↗
PubMed1988

Use of routine chest radiography in the evaluation of fever in neutropenic pediatric oncology patients.

Evaluation of febrile episodes in children who have become neutropenic during treatment for malignant disease has traditionally included radiography of the chest. It has been our impression that the yield of such examination is low. To test this hypothesis we reviewed all chest radiographs (CXRs) obtained in the above setting in our institution over the last 3 years. These radiographs were independently reviewed by two of us (R.C., J.F.). Sixty-one patients experienced 134 febrile neutropenic episodes for which a CXR was obtained. Only eight (6%) of these films revealed any abnormality. After careful review it was apparent that four of these radiographs did not represent a infectious process. Thus only four of 134 films (2.9%) indicated pulmonary infection as the probable cause of fever in the patient. All four of these patients had prominent respiratory signs or symptoms. Of patients who were febrile but without pulmonary signs/symptoms, only one of 49 had an abnormal radiograph. We feel that such a low yield (at most 2%) calls into question the routine practice of obtaining a CXR in the febrile neutropenic child who is otherwise asymptomatic.

Adolescent↗
PubMed1987

Hypertension in neuroblastoma induced by imipramine.

Hypertension is a well-known finding in some patients with neuroblastoma. However, it has not previously been described in association with the use of Imipramine. We report the occurrence of severe hypertension (blood pressure 190/160) in a 4-year-old girl with neuroblastoma who was given Imipramine to control a behavior disorder. It was determined later that this patient's tumor was recurring at the time of her hypertensive episode. Since she had no blood pressure elevation at initial diagnosis and none following discontinuation of the Imipramine (when she was in florid relapse), we believe that this drug rather than her underlying disease alone caused her hypertension. The mechanism for this reaction is believed to be increased levels of vasoactive catecholamines due to interference of their physiologic inactivation by Imipramine. From this experience, we urge extreme caution in the use of tricyclic antidepressants in children with active neuroblastoma.

Adrenal Gland Neoplasms↗
PubMed1986

Bone marrow transplantation for children with acute leukemia and Down syndrome.

Four children with acute leukemia and Down syndrome received high-dose cyclophosphamide therapy and total body irradiation in preparation for bone marrow transplantation. Skin and mucous membrane toxicity was pronounced. Furthermore, three children died during the immediate posttransplantation period of infectious and hemorrhagic pulmonary complications. One patient had hematologic recovery and is surviving disease-free 1 year following transplantation. These preliminary observations are in agreement with previous data suggesting that children with Down syndrome are at higher risk for toxicity, pneumonitis, and, possibly, death following administration of intensive therapy for leukemia in comparison with children without Down syndrome. Improvements in the management of these children in the future will depend upon a better understanding of the biologic and pathophysiologic aspects of Down syndrome and additional clinical experience.

Adolescent↗