The 19th Australian & New Zealand scientific meeting on intensive care conference report.
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Biomedical subjects
Publications and source records attributed to A Coleman.
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After adaptation of a mouse plasma cell tumor, MOPC265, to culture, we have found several unique chromosomal alterations in addition to the T(12;15) translocation and trisomy 11 frequently observed in plasmacytomas. Among these alterations is a specific coamplification of the c-Myc and Pvt 1 gene loci from mouse chromosome 15. Further analysis by fluorescence in situ hybridization demonstrates that the amplicons of c-Myc and Pvt 1 exist as extrachromosomal elements as well as within intact chromosomes. Most importantly, the presence of both Pvt 1 and c-Myc in these extrachromosomal elements indicates ongoing coselection for these loci in the propagation of MOPC265.
The development of malignant melanoma is accompanied by an accumulation of genetic damage that is evident within tumor cells at both cytogenetic and molecular levels, and mutations at several gene loci are thought to contribute to malignant progression. Some of these loci are known oncogenes and tumor suppressor genes; others remain to be identified, although their chromosomal locations have been determined. Gene mapping studies indicate the presence of melanoma tumor suppressor genes on chromosomes 1, 6, and 9. The presence of a tumor suppressor gene on a particular chromosome can be demonstrated by transfer of an intact, normal copy of the chromosome into tumor cells. We have used this approach to investigate the mechanisms by which chromosome 6 suppresses the growth and tumorigenicity of human malignant melanoma cells.
Deletions of DNA on chromosome 9p21-22 are frequently observed in cells derived from melanomas, gliomas, non-small cell lung cancers, and acute lymphoblastic leukemia. The minimal deletion shared by the latter three cancers extends from the interferon-alpha locus towards the centromere; its centromeric end is flanked by the gene encoding methylthioadenosine phosphorylase. We have determined that the telomeric end of the minimal homozygous deletion shared by two melanoma cell lines does not include the methylthioadenosine phosphorylase locus. Thus, a distinct region of DNA is lost in melanoma. The physical size of this region remains to be defined precisely, but it may extend over several million base pairs.
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We report a patient who, at age 38, presented with temporal lobe seizures and an atypical memory disorder 3 years before the discovery of a testicular tumor. Detailed neuropsychological testing revealed a relatively isolated amnestic syndrome. The amnesia was atypical as the patient could retain information for hour-long periods, only to lose it later. Serologic studies revealed the presence of a circulating autoantibody that demonstrated an unusual affinity for the nucleolus of cerebral cortical neurons. Western blot analysis of cortical neurons revealed that this antibody reacted with proteins different from other previously identified paraneoplastic neurologic antigens (Hu, Yo, Ri). We believe this to be a case of paraneoplastic limbic encephalitis secondary to the testicular tumor. This patient presents unique characteristics with respect to the mode of presentation, features of the amnesia, and the presence of a circulating antibody with an unusual reactivity pattern.
We describe a new technique for the measurement of retinal nerve fiber layer thickness and compare its results with histopathologic measurements in the same eyes. For these studies, two fixed monkey eyes were incised and placed on a pedestal in a plastic viewing dish. The eyes were perfused to maintain a pressure between 10 and 20 mm Hg. An ellipsometer, an optical device used to measure the change in polarization of light (retardation), was implemented in a laser tomographic scanner to obtain polarization data from the two monkey retinas. For the 15 measured locations, retardation ranged between a mean (+/- SD) of 0.9 degrees +/- 1.8 degrees and 23.7 degrees +/- 0.3 degrees. Subsequently, retinal nerve fiber layer thickness was measured at the imaged points in epoxy resin-embedded sections by an observer masked to the ellipsometry data. These values ranged between 20.4 microns and 213.9 microns. There was an excellent correlation (R = .83) between retardation and the histopathologic measurement of retinal nerve fiber layer thickness. Quantitating retinal nerve fiber layer thickness may enhance discrimination between glaucomatous and normal eyes earlier than is currently available by anatomic and functional approaches.
Twenty-seven patients with open-lung biopsy findings consistent with extrinsic allergic alveolitis (hypersensitivity pneumonitis) were studied. In only one case had the diagnosis been considered prior to the biopsy. Among the 27 patients, a causative exposure was subsequently identified in 10, and no apparent cause could be found in the remaining 17. The prognosis for the entire group was good; all 10 patients in whom an exposure was found and 13 of 17 without causative exposure are alive without progressive lung disease.
A case of adult aleukemic leukemia with an isolated CNS relapse diagnosed by cytologic examination of the CSF is reported. CSF hypereosinophilia of uncertain significance was documented. Immunologic marker studies (CALLA, HTA, Tdt) were performed on the CSF and showed a null cell acute lymphocytic leukemia. Sequential CSF specimens were obtained to determine the continued presence of lymphoblasts. Cytologic monitoring of the CSF in acute leukemia is a useful technique to determine disease status and efficacy of therapy. We advocate the use of cell morphology for monitoring, reserving the use of cell markers for initial identification of malignant cells and for use when the cell morphology is altered.
Fluoxetine, a selective serotonin uptake inhibitor (mean dose 73 mg each morning) was compared with amitriptyline (mean dose 122 mg at night) in a double-blind study of 64 depressed out-patients. Fifty patients completed the 6-week trial. The drugs did not differ with respect to psychiatrists' ratings, but amitriptyline was slightly superior with respect to patients' ratings. The amitriptyline-treated group had complaints of dry mouth and dizziness on standing; the fluoxetine-treated group of sleep disturbances, nausea, and headaches.
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A behavioral management system designed to reduce urinary incontinence was evaluated in two nursing homes with a pretest-posttest control group design with repeated measures. The primary components of the system were prompting and contingent social approval/disapproval which required approximately 2.5 minutes per patient per hour to administer. The frequency of correct toileting for experimental subjects increased by approximately 45%. The experimental groups were significantly different from the control groups on both incontinence and correct toileting measures. The results are discussed in view of the management issues inherent in nursing home settings.
In experiment 1, children between the ages of 6 and 9 years binocularly viewed red vertical and green horizontal gratings for several minutes. This would, in adults, produce a reliable orientation-specific McCollough effect, and it was present in the children. In experiment 2, a second group of children viewed the adaptation patterns with only 1 eye, the other eye being occluded. The McCollough effect was present when the adapted eye viewed the test pattern, but, as in adults, no interocular transfer was found.
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In organizations with the power to persist through turbulent eras, one finds leaders who live as if they were stewards of a legacy-the culture, mission, and founding spirit of the organization. These legacy leaders may be physicians, administrators, chief executives, or board members, but they all have the ability to weave a thread of constancy through times of peril. Five attributes characterize legacy leaders: Their work is a vocation, they possess a moral code, they are committed to stewardship, they have a bias for building, and they instill hope. Legacy leaders stay with one organization a very long time, patiently removing obstacles to worthy accomplishments. Because the profession of healthcare is at heart a vocation, not a business, we must pay attention to the kinds of leaders we place in our healthcare institutions. To carry out their responsibility of transforming healthcare delivery, boards of directors must hire legacy leaders, manage their business focus, carefully evaluate executives, enhance mechanisms for board evaluation, and raise the bar for decision making.