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Biomedical subjects

R S Morrison

Publications and source records attributed to R S Morrison.

At least 55 records · Page 3Linked to original sources
PubMed1998

[Inhibition of fibroblast growth factor receptor 1 expression in human glioblastoma cell contributes to the cell growth suppression].

Although normal human astrocytes rarely express fibroblast growth factor receptor 1 (FGFR 1) mRNA, expression of FGFR 1 mRNA in astrocytomas increases as malignancy progresses. This result suggests that FGFR 1 can be one of important factors for glioblastoma cell growth. In our study, specific antisense oligonucleotides for FGFR 1 mRNA inhibited cell growth of SNB 19, human glioblastoma cell line, while sense oligonucleotides showed no cell reduction. And Southern blot analysis demonstrated decreased expression of FGFR 1 mRNA in only antisense group. Furthermore, cross-linking analysis revealed decreased number of FGFR 1 in antisense-treated SNB 19 in protein level. These results conclude that cell growth inhibition was caused by suppression of both transcription and translation of FGFR 1 mRNA. Interestingly, alpha-specific antisense also inhibited expression of beta-, and gamma-type of FGFR 1 mRNA which had no binding sites for the oligonucleotides. This fact indicates that antisense oligonucleotides binds to premature mRNA, which is previous form of mature mRNA before splicing, in nucleus. It is previously reported that basic fibroblast growth factor (bFGF), major ligand to FGFR 1, was overly expressed in human malignant astrocytomas. Thus, increased number of FGFR 1 may contribute to the acceleration of bFGF autocrine or paracrine mechanism in glioblastoma.

Brain Neoplasms↗
PubMed1997

Improving palliative care.

Although most deaths in the United States occur in hospitals, data suggest that hospitals and physicians are not equipped to handle the medical and psychosocial problems of dying patients. In this article, we review the barriers to achieving a peaceful death, including inadequate medical professional education on palliative care, and public and professional uncertainty about the difference between foregoing life-sustaining treatment and active euthanasia, and health professionals' difficulty recognizing when patients are dying and the associated sense that death is a professional failure. Other barriers include fiscal constraints on the length of stay, the number of nurses available to care for dying patients, legal and regulatory constraints on obtaining opioid prescriptions, and a segregated system of hospice care that requires patients to be separated from familiar health care providers and settings in order to receive palliative care at the end of life. Identifying the opportunities that can improve the delivery of palliative care at the end of life is the first step toward developing corrective approaches. Strategies that enhance these opportunities are proposed.

Attitude of Health Personnel↗
PubMed1997

Sequence requirements for regulated RNA splicing of the human fibroblast growth factor receptor-1 alpha exon.

Progression of astrocytes from a benign to a malignant phenotype is accompanied by a change in the RNA processing of the fibroblast growth factor receptor 1 (FGFR-1) gene. The level of a high affinity form of the FGFR-1 is dramatically elevated as a result of alpha-exon skipping during RNA splicing. In this paper we have been able to duplicate this tumor-specific RNA processing pathway by transfection of a chimeric minigene containing a 4-kilobase fragment of the human FGFR-1 gene (including the alpha-exon) into a variety of cell lines. In a transfected human astrocytoma cell line, alpha-exon skipping was consistently observed for RNA transcripts derived from both the chimeric minigene and endogenous gene expression. This exon skipping phenotype was dependent on the size of the flanking intron as deletions which reduced the introns to less than approximately 350 base pairs resulted in enhanced alpha-exon inclusion. Increased exon inclusion was not sequence-specific as exon skipping could be restored with insertion of nonspecific sequence. Cell-specific exon recognition was maintained with a 375-nucleotide sequence inclusive and flanking the alpha-exon, provided that intron size was maintained. These results identify the minimal cis-regulatory sequence requirements for exclusion of FGFR-1 alpha-exon in astrocytomas.

Base Sequence↗
PubMed1997

Identification of nursing management diagnoses.

Theories from nursing and management provide frameworks for enhancing effectiveness of nursing management practice. The concept nursing management diagnosis has been developed by integrating nursing diagnosis and organizational diagnosis as a basis for nurse manager decision-making. Method triangulation was used to identify problems of managing nursing units, to validate those problems for relevancy to practice, to generate nursing management diagnoses, and to validate the diagnoses. Diagnoses were validated according to a definition of nursing management diagnosis provided. Of the 72 nursing management diagnoses identified, 66 were validated at a 70% level of agreement by nurse managers participating in the study.

Decision Making↗
PubMed1997

The relation between leadership style and empowerment on job satisfaction of nurses.

OBJECTIVE: The authors explore the relation between leadership style and empowerment and its effect on job satisfaction among the nursing staff of a regional medical center. BACKGROUND: Several empirical studies on transformational leadership-found that transformational leadership behaviors were positively related to work team success and leadership effectiveness. Transformational leadership processes have also been suggested to enhance followers' work-oriented values and shape the self-efficacies of followers. Employee empowerment may be influenced by the perception that the organization cares about its employees' well-being and that their work is valued. Empowering nurses may increase job satisfaction and improve patient care. Leadership style and empowerment influence job satisfaction among workers. METHODS: All nursing department staff were invited to complete a self-report questionnaire with no identifying information. Leadership style was measured using Bass's Multifactor Leadership Questionnaire, empowerment was measured with items from Spreitzer's Psychological Empowerment instrument, and job satisfaction was measured by Warr, Cook, and Wall's job satisfaction questionnaire. RESULTS: Both transformational and transactional leadership were positively related to job satisfaction, as was empowerment. Differences in the contributions of empowerment and leadership style in predicting job satisfaction for licensed and unlicensed workers was evident. CONCLUSION: Designing interventions that allow for the relative influence of leadership style as well as empowerment on varying classifications of nursing personnel may be a more effective strategy and have a greater effect on staff attitudes and behaviors.

Decision Making, Organizational↗
PubMed1997

Advance directives: when, why, and how to start talking.

Advance directives allow patients to influence their medical care after they have lost decision-making capacity. As it is impossible to predict a life-threatening event, physicians should address advance directives with every patient during routine office visits. To make informed decisions, patients must understand their options, such as CPR and artificial nutrition and hydration. Similarly, physicians need to understand patients' values and goals, in order to counsel proxy decision-makers and guide their patients' care. Two office visits are recommended; experienced physicians can usually accomplish the initial conversation in less than 10 minutes and the follow-up in less than 5 minutes. Because opinions and circumstances change, these documents should be reviewed annually.

Advance Directives↗
PubMed1996

Evidence for p53-mediated modulation of neuronal viability.

A role for p53-related modulation of neuronal viability has been suggested by the finding that p53 expression is increased in damaged neurons in models of ischemia and epilepsy. These findings were recently extended with the demonstration that mice deficient in p53 ("knock-out" mice) exhibit almost complete protection from seizure-induced brain injury, whereas wild-type mice display significant neuronal cell loss in the hippocampus and other brain regions. Because the p53 knock-out mice used in the latter study expressed a global p53 deficiency in all cell types, it was not possible to conclude that protection was conferred by the exclusive absence of p53 in neurons. Therefore, in the present study, we determined whether p53 expression in isolated neurons is directly coupled to a loss of viability associated with excitotoxic challenge. Primary cultures of hippocampal or cortical neurons were derived from animals containing p53 (+/+, +/-) or those deficient in p53 (-/-). p53-Deficient neurons appeared identical to wild-type neurons with respect to morphology, neurofilament expression, and resting levels of intracellular calcium. Neurons containing at least one copy of p53 were severely damaged by exposure to kainic acid or glutamate. Cell damage was assessed by direct cell counting and by nuclear morphology after propidium iodide staining of DNA. In contrast, neurons deficient in p53 (-/-) exhibited little or no damage in response to excitotoxin treatment. Despite their divergent outcomes, p53 (+/+) and p53 (-/-) neurons demonstrated similar sustained elevations in intracellular calcium levels triggered by glutamate exposure. Restoring p53 expression to p53-deficient neurons, using adenovirus-mediated transduction, was sufficient to promote neuronal cell death even in the absence of excitotoxin. These results demonstrate a direct relationship between p53 expression and loss of viability in CNS neurons.

Animals↗
PubMed1996

Treatment of the dying in the acute care hospital. Advanced dementia and metastatic cancer.

BACKGROUND: Most Americans die in the acute care hospital, where aggressive, life-prolonging interventions are readily performed. Although patients with incurable illness might prefer palliative care, perceived differences in prognosis by physicians may influence the type of care provided. Patients with advanced cancer and advanced dementia represent 2 extremes in the use of hospice services and may also be treated differently in the acute care hospital. We tested this hypothesis and quantitated the use of nonpalliative interventions in hospitalized, incurably ill patients. METHODS: Charts of elderly patients with advanced dementia or metastatic solid tumor malignancy who died during a 13-month period in a tertiary care acute teaching hospital were reviewed. Main outcome measures included the number of patients receiving invasive of noninvasive (but complex) diagnostic tests, invasive nonpalliative treatments, cardiopulmonary resuscitation, systemic antibiotics, and do-not-resuscitate orders. RESULTS: Charts of 164 patients (80 with dementia and 84 with cancer) were reviewed. Overall, 47% received invasive nonpalliative treatments. Controlling for age, sex, length of stay, and insurance status, the groups were equally likely to receive nonpalliative treatments (P = .75), but patients with dementia were more likely to receive new feeding tubes (P = .02). Cardiopulmonary resuscitation was attempted for 24% of each group. Patients with cancer more often received invasive (41% vs 13%; P = .002) and complex noninvasive diagnostic tests (49% vs 23%; P = .02). Overall, 88% received antibiotics, often empirically, but, controlling for neutropenia and invasive tests and treatments, patients with dementia were significantly more likely to receive antibiotics for an identifiable infection (P = .004). CONCLUSIONS: Incurably ill patients often receive nonpalliative interventions at the end of life. Patients with cancer receive more diagnostic tests, but patients with dementia receive more enteral tube feeding. Patients commonly receive systemic antibiotics, often empirically. Cardiopulmonary resuscitation is equally applied, but is out of proportion to expected survival.

Advance Directives↗
PubMed1996

bFGF enhances the protective effects of MK-801 against ischemic neuronal injury in vitro.

The neuroprotective activity of basic fibroblast growth factor (bFGF) in combination with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 was evaluated in organotypic hippocampal slice cultures. Oxygen/glucose deprivation produced neuronal damage which was assessed using propidium iodide fluorescence. Treatment with increasing doses of bFGF demonstrated significant neuroprotection that was optimal at 10 ng ml-t. This effect was diminished at higher concentrations. MK-801, at the optimal concentration of 30 microM, demonstrated greater neuroprotective efficacy than bFGF. However, bFGF significantly enhanced the protection conferred by MK-801 alone. These results suggest that neurotrophic factors such as bFGF may augment the neuroprotective effects of NMDA antagonists against ischemic neuronal injury.

Animals↗
PubMed1996

Marked improvement in recognition and completion of health care proxies. A randomized controlled trial of counseling by hospital patient representatives.

BACKGROUND: Advance directives provide a means for patients to retain influence on their medical care should decisional capacity be lost. Several studies have now demonstrated that advance directives that are completed in the ambulatory care setting are rarely available and recognized when patients are admitted to the acute care hospital. OBJECTIVE: To evaluate a generalizable model for improving recognition of previously completed advance directives and for promoting appointment of health care proxies in hospitalized patients. METHODS: Hospitalized elderly patients were randomly assigned to receive the intervention or usual care (n = 190). Intervention patients with capacity were counseled by hospital patient representatives about advance directives and encouraged to complete health care proxies. Patients with existing proxies had this information noted in their charts. For patients without capacity, counselors reviewed their charts for proxy documentation and if absent, contacted patients' next of kin and private physicians to determine proxy status. Usual care patients were not contacted by patient representatives. RESULTS: Forty-eight percent of intervention patients completed a new proxy or had a previously completed proxy identified compared with 6% of controls (P < .001). For patients with capacity, 22% of intervention patients had a previously appointed proxy agent identified compared with 6% of controls (P < .001). Thirty-six percent of intervention patients appointed a proxy decision maker compared with 0% of controls (P < .02). For patients without capacity, 31% of intervention patients had previously appointed proxies identified compared with 6% of controls (P < .001). CONCLUSIONS: Counseling by hospital patient representatives is an effective and generalizable means of improving recognition and execution of advance directives in the acute care hospital.

Advance Directives↗
PubMed1996

Loss of the p53 tumor suppressor gene protects neurons from kainate-induced cell death.

The tumor suppressor gene p53 recently has been associated with the induction of cell death in response to some forms of cellular damage. A possible role for p53-related modulation of neuronal viability has been suggested by the finding that p53 expression is increased in damaged neurons in models of ischemia and epilepsy. We evaluated the possibility that p53 expression (in knockout mice) is required for induction of cell damage in a model of seizure activity normally associated with well defined patterns of cell loss. Subcutaneous injection of kainic acid, a potent excitotoxin, induced comparable seizures in both wild-type mice (+/+) and mice deficient in p53 (-/-). Using a silver impregnation technique to examine neurodegeneration in animals killed 7 d after kainate injection, we found that a majority of +/+ mice exhibited extensive cell loss in the hippocampus, involving subregions CA1, CA3, the hilus, and the subiculum. Apoptotic cell death, as identified with an in situ nick end labeling technique to detect DNA fragmentation, was confirmed in CA1- but not CA3-degenerating neurons. In marked contrast, a majority of p53 -/- mice displayed no signs of cell damage; in the remaining p53 -/- mice, damage was mild to moderate and was confined almost entirely to cells in CA3b of the dorsal hippocampus. In +/+ mice, but not in -/- mice, damaged neurons also were observed in the amygdala, piriform cortex, cerebral cortex, caudate-putamen, and thalamus after kainate treatment. The pattern and extent of damage in mice heterozygous for p53 (+/-) were identical to those seen in +/+ mice, suggesting that a single copy of p53 is sufficient to confer neuronal vulnerability. These results demonstrate that p53 influences viability in multiple neuronal subtypes and brain regions after excitotoxic insult.

Animals↗
PubMed1996

Regulation of FGF receptors in the oligodendrocyte lineage.

Fibroblast growth factors (FGFs) affect a broad spectrum of developmentally regulated cellular responses involved in the control of growth and differentiation. To identify specific FGF receptor forms involved in these responses, we have characterized FGF receptor transcript expression, and its modulation by FGF-2, as enriched populations of oligodendrocyte progenitors differentiate into mature oligodendrocytes. The data demonstrate that the levels of mRNA expression for FGF high-affinity receptors-1, -2, and -3 are differentially regulated during lineage progression: FGF receptor-1 expression increases with lineage progression, FGF receptor-2 is predominantly expressed by terminally differentiated oligodendrocytes, and FGF receptor-3 reaches a peak level of expression in late progenitors and then declines upon further differentiation; FGF receptor-4 expression was not detected in oligodendrocytes. Distinct patterns of alternatively spliced variants of FGF receptor-1 and -2 transcripts are expressed: the predominant FGF receptor-1 transcripts contain three Ig-like domains (FGF receptor-1 alpha), whereas the FGF receptor-2 transcripts contain two Ig-like domains (FGF receptor-2 beta 2) and this form is up-regulated as oligodendrocytes differentiate. In addition, the expression of these receptors is differentially regulated by the ligand, FGF-2: FGF receptor-1 mRNA expression is up-regulated in early progenitors, and FGF receptor-2 mRNA expression is down-regulated in mature oligodendrocytes. Finally, astrocytes express FGF receptor-1, -2, and -3 transcripts, but at different levels and with different exon utilization (FGF receptor-1 beta, FGF receptor-2 beta 1/beta 2) compared to oligodendrocytes. To our knowledge this is the first report that demonstrates that the mRNA expression of these three FGF receptor types is differentially regulated in primary cells as they differentiate along a lineage from progenitors to terminally differentiated cells. We propose that this pattern of expression provides a molecular basis for the developmentally varying response of cells to a common ligand. For example, according to this hypothesis, in response to FGF-2, FGF receptor-1 transduces signals that stimulate the prolonged proliferation and migration of early progenitors, FGF receptor-3 promotes the proliferation and arrest of differentiation of late progenitors, and FGF receptor-2 transduces signals for terminal differentiation, but not proliferation, in mature oligodendrocytes.

Alternative Splicing↗
PubMed1996

Palliative medicine: providing care when cure is not possible. A roundtable discussion: Part I.

Palliative medicine describes the care of patients with advanced disease. When cure is no longer possible, the goal becomes control of pain, other symptoms, and psychological distress. In the United States, palliation has been pioneered by the hospice movement for patients with disseminated cancer and AIDS. Palliative care is also appropriate for patients with many of the chronic diseases of aging. For medical, humanitarian, financial, and legal reasons, physicians are being called on to provide palliative care when they make the diagnosis of all illness that is unresponsive to curative treatment.

Acquired Immunodeficiency Syndrome↗
PubMed1996

A peaceful death: how to manage pain and provide quality care. A roundtable discussion: Part 2.

One of the most important components of a peaceful death is adequate control of pain and other distressing symptoms, such as dyspnea, agitation, and restlessness. Pain is an important symptom in 75 to 80% of noncancer patients in the last year of life. Opioid analgesics are often the mainstay of pain treatment for dying patients. A primary care physician also needs to know about anesthetic and neurosurgical approaches, the use of cognitive behavioral approaches, and the availability of specialized pain experts. A sizeable minority of physicians receive requests for an assisted death, which should be seen as a cry for help. The most useful function of advance directives is that they open an avenue for discussion between the doctor and the patient about a difficult subject.

Analgesics, Opioid↗
PubMed1996

[Expression of fibroblast growth factor receptors (FGFRs) mRNA in human astrocytomas].

Although fibroblast growth factor receptor (FGFR) 4 has been reported not to be expressed in normal human astrocytes, we have demonstrated expression of FGFR-1, -3, and -4 in six human glioblastoma cell lines (SNB19, T98G, UW18, D54 MG, U251MG, and U373MG) by RT-PCR Southern blot analysis. All six lines exhibited predominantly beta-type (with only two extracellular Ig-like domains) FGFR-1 expression. In contrast, FGFR-2 expression was only detected in the UW18 cell line. This evidence support our previous observation that malignant progression in astrocytomas is associated with a shift in FGFR-1 mRNA splicing from the alpha-type (with three extracellular Ig-like domains) to the beta-type with concomitant loss of FGFR-2 expression. It also demonstrates the unique finding that FGFR-4 induction in astrocytomas is associated with transformation. In addition to these cell lines, expression of FGFRs was analyzed in normal human brain tissue and in human astrocytoma tissue samples corresponding to different grades of malignancy. FGFR-4 mRNA was undetectable in normal adult white matter, the site of origin of astrocytomas, while astrocytomas of all grades exhibited significant expression of FGFR-4 mRNA as determined by RT-PCR Southern blot analysis. The proportion of FGFR-4 mRNA did not appear to change in relation to the malignant progression of the astrocytomas. This suggests that induction of FGFR-4 expression in astrocytes represents an early event in their malignant transformation. Induction of FGFR-4 in malignant astrocytomas is consistent with previous reports demonstrating that expression of aFGF, which activates FGFR-4, increases in astrocytomas. The simultaneous induction of FGFR-4 and aFGF may establish a potential autocrine pathway that endows astrocytoma cells with a selective growth advantage. Interestingly, very high expression of FGFR-4 mRNA was found in human fetal brain tissue. The above findings suggest that the malignant transformation of astrocytes may involve the activation of a fetal growth promoting pathway.

Aged↗
PubMed1995

The inaccessibility of advance directives on transfer from ambulatory to acute care settings.

OBJECTIVE: To investigate the accessibility of patients' previously executed advance directives during an acute hospitalization. DESIGN: Retrospective chart review. SETTING: A large metropolitan teaching hospital, a 514-bed skilled nursing facility, a geriatrics ambulatory care clinic, and a geriatrics group practice office. PATIENTS: One hundred fourteen geriatric patients who had previously executed an advance directive. MAIN OUTCOME MEASURES: The medical records of 180 admissions over 3 years, 1991 through 1993, were reviewed for documentation of patients' advance directive status. RESULTS: Twenty-six percent of patients who had previously executed advance directives had their directives recognized during their hospitalization. Of the subgroup of patients who were judged not to have the capacity to make medical decisions during their admissions, 26% (14/53) had their directives recognized. When the advance directive was recognized, it appeared to influence treatment decisions in 12 (86%) of 14 cases. CONCLUSIONS: Previously executed advance directives are not accessible when patients are admitted to hospitals for acute illness. When such directives are recognized, they are used to influence medical treatment decisions. Further research is needed to define and overcome barriers to this inaccessibility.

Advance Directives↗
PubMed1995

Expression of basic fibroblast growth factor in squamous cell carcinoma of the head and neck is associated with degree of histologic differentiation.

Basic fibroblast growth factor (bFGF) is a potent nitogen and angiogenic protein that may function as an autocrine growth regulator in a variety of malignancies. Expression of bFGF in squamous cell carcinoma of the head and neck (SCCHN) was characterized by Western blot and immunohistochemical analyses. We found that the levels of bFGF in tumors were the same or reduced relative to non-malignant adjacent mucosa. Reverse transcription-polymerase chain reaction and Southern blot transfer of mRNA derived from 7 SCCHN cell lines showed that the IIIb isoform of FGF-receptor 2 (FGFR2) was expressed at high levels, whereas the IIIc isoform and FGFRI were weakly expressed or not detected. No correlation was observed between levels of bFGF revealed by immunohistochemical staining and vascular counts in frozen sections derived from 11 different SCCHN tumors. Immunohistochemical analysis demonstrated that all differentiated tumors exhibited high levels of bFGF immunoreactivity, while all poorly differentiated tumors exhibited low to nondetectable levels. This expression pattern is consistent with that observed in non-tumoral mucosa and suggests that other angiogenic factors must play a predominant role in the development of poorly differentiated SCCHN.

Antibodies, Monoclonal↗