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Biomedical subjects

R S Morrison

Publications and source records attributed to R S Morrison.

At least 37 records · Page 2Linked to original sources
PubMed2000

Complementary and alternative medicine in the management of pain, dyspnea, and nausea and vomiting near the end of life. A systematic review.

To review the evidence for efficacy of complementary and alternative medicine (CAM) modalities in treating pain, dyspnea, and nausea and vomiting in patients near the end of life, original articles were evaluated following a search through MEDLINE, CancerLIT, AIDSLINE, PsycLIT, CINAHL, and Social Work Abstracts databases. Search terms included alternative medicine, palliative care, pain, dyspnea, and nausea. Two independent reviewers extracted data, including study design, subjects, sample size, age, response rate, CAM modality, and outcomes. The efficacy of a CAM modality was evaluated in 21 studies of symptomatic adult patients with incurable conditions. Of these, only 12 were directly accessed via literature searching. Eleven were randomized controlled trials, two were non-randomized controlled trials, and eight were case series. Acupuncture, transcutaneous electrical nerve stimulation, supportive group therapy, self-hypnosis, and massage therapy may provide pain relief in cancer pain or in dying patients. Relaxation/imagery can improve oral mucositis pain. Patients with severe chronic obstructive pulmonary disease may benefit from the use of acupuncture, acupressure, and muscle relaxation with breathing retraining to relieve dyspnea. Because of publication bias, trials on CAM modalities may not be found on routine literature searches. Despite the paucity of controlled trials, there are data to support the use of some CAM modalities in terminally ill patients. This review generated evidence-based recommendations and identified areas for future research.

Complementary Therapies↗
PubMed2000

The role of p53 in neuronal cell death.

The p53 tumor suppressor gene is a sequence-specific transcription factor that activates the expression of genes engaged in promoting growth arrest or cell death in response to genotoxic stress. A possible role for p53-related modulation of neuronal viability has been suggested by the finding that p53 expression is elevated in damaged neurons in acute models of injury such as ischemia and epilepsy and in brain tissue samples derived from patients with chronic neurodegenerative diseases. Moreover, the absence of p53 has been shown to protect neurons from a wide variety of acute toxic insults. Signal transduction pathways associated with p53-induced cell death are being unraveled and suggest that intervention may prove fruitful in maintaining neuronal viability and restoring function following cytopathic insults.

Animals↗
PubMed2000

Palliative care in advanced dementia: a randomized controlled trial and descriptive analysis.

BACKGROUND: Few patients with end-stage dementia are enrolled in hospice care. A palliative care approach would nonetheless seem to be appropriate in various care settings, including the acute care hospital. METHODS: We conducted a randomized controlled trial of palliative care in patients with advanced dementia (Functional Assessment Staging Tool [FAST] stage 6d-7f) who were hospitalized with acute illness. Intervention patients received recommendations by a palliative care team with the goal of enhancing patient comfort; control patients received usual care without these recommendations. RESULTS: Among 99 patients enrolled over 3 years, groups were comparable at baseline in terms of gender, age, race, dementia stage, and advance directive status. Outcomes were similar in terms of mean number of hospitalizations, average length of stay, and mortality. Intervention patients were more likely than control patients to receive a palliative care plan (23% versus 4%; p = 0.008), usually on discharge, and more decisions were made to forgo certain medical treatments but the numbers were small. Fewer patients in the intervention group received intravenous therapy throughout the admission (66% vs. 81%, p = 0.025). Overall, additional interventions included daily phlebotomy for at least half of the admission (41%), systemic antibiotics (75%), and new feeding tubes (44%). Including tubes present at the time of randomization, a total of 69% received long-term enteral feeding. CONCLUSION: It was difficult for a palliative care research team to influence the care of advanced dementia patients in the acute hospital setting. When patients have advanced dementia, there may be unique barriers, including perceived prognostic uncertainty, difficulty assessing comfort level, and perceptions about tube feeding. There must be a reexamination of treatment approaches for this severely impaired group of patients. Further study should attempt to identify patients prior to the need for acute hospitalization so goals can be established when there is less urgency to make life and death decisions.

Journal Article↗
PubMed2000

Delirium on hospital admission in aged hip fracture patients: prediction of mortality and 2-year functional outcomes.

BACKGROUND: Hip fracture patients are at increased risk of confusion or delirium due to the trauma associated with the injury and the rapid progression to hospitalization and surgery, in addition to the pain and loss of function experienced. Hip fracture patients who develop delirium may require longer hospital stays, are more often discharged to long-term care, and have a generally poor prognosis for returning home or regaining function in activities of daily living (ADL). METHODS: The present study examines the impact of delirium present on hospital admission in a sample of 682 non-demented, aged hip fracture patients residing in the community at the time of their fracture. In-hospital assessments designed to assess both prefracture and postfracture functioning, as well as follow-up interviews at 2, 6, 12, 18, and 24 months postfracture, were obtained from participants. RESULTS: Analyses indicate that baseline or admission delirium is an important prognostic predictor of poor long-term outcomes in persons without known cognitive impairment, after controlling for age, gender, race, comorbidity, and functional status. Delirium at admission (i.e., prior to surgery) was associated with poorer functioning in physical, cognitive, and affective domains at 6 months postfracture and slower rates of recovery. Impairment and delays in recovery may be further exacerbated by increased depressive symptoms in confused patients over time. Delirium on hospital admission was not a significant predictor of mortality after adjustment for confounding factors. CONCLUSIONS: The present findings further emphasize the significance of immediate detection and treatment of delirium in hip fracture patients to ameliorate the short and long-term effects of acute confusion on functional outcomes.

Activities of Daily Living↗
PubMed1999

Contribution of p53-dependent caspase activation to neuronal cell death declines with neuronal maturation.

Caspases play a pivotal role in neuronal cell death during development and after trophic factor withdrawal. However, the mechanisms regulating caspase activity and the role played by caspase activation in response to neuronal injury is poorly understood. The tumor suppressor gene p53 has been implicated in the loss of neuronal viability caused by excitotoxic and DNA damaging agents. In the present study we determined if p53-mediated neuronal cell death required caspase activation. DNA damage increased caspase activity in both cultured embryonic telencephalic and postnatal cortical neurons in a p53-dependent manner. Caspase inhibitors protected embryonic telencephalic neurons, but not postnatal cortical neurons, from DNA damage-induced cell death as measured by direct cell counting and annexin V staining. In marked contrast to the caspase inhibitors, an inhibitor of the DNA repair enzyme, poly(ADP-ribose) polymerase, conferred significant protection from genotoxic and excitotoxic cell death on postnatal cortical neurons but had no effect on embryonic neurons. Glutamate-mediated excitotoxicity in postnatal neurons was not associated with measurable changes in caspase activity, consistent with the failure of caspase inhibitors to prevent cell death under these conditions. Moreover, adenovirus-mediated overexpression of p53 killed embryonic and postnatal neurons without activating caspases. Thus, p53-mediated neuronal cell death may occur via both caspase-dependent and caspase-independent pathways. These results demonstrate that p53 is required for caspase activation in response to some forms of neuronal injury. However, the relative importance of caspase activation in neurons depends on the developmental status of the cell and the specific nature of the death stimulus.

Adenoviridae↗
PubMed1999

Mechanisms of hypoxia-induced endothelial cell death. Role of p53 in apoptosis.

Endothelial cell death may contribute to tissue injury from ischemia. Little is known, however, about the characteristics of endothelial cell death in response to hypoxia. Using an in vitro model, we found that human umbilical vein endothelial cells were resistant to hypoxia-induced cell death with only a 2% reduction in viability at 24 h and 45% reduction in viability at 48 h. Overexpression of a mutant, IkappaBalpha, via adenoviral vector did not potentiate cell death in hypoxia, indicating that nuclear factor-kappaB activation was not involved in cytoprotection. Cell death in hypoxia was determined to be apoptotic by 3' labeling of DNA using terminal deoxynucleotidyl transferase staining and reversibility of cell death with a caspase inhibitor. Exposure of endothelial cells to hypoxia did not alter levels of proapoptotic and antiapoptotic Bcl-2 family members Bax and Bcl-XL by immunoblot analysis. In contrast, changes in p53 protein levels correlated with the induction of apoptosis in hypoxic endothelial cells. Inhibition of the proteasome increased p53 protein levels and accelerated cell death in hypoxia. Overexpression of p53 by adenoviral transduction was sufficient to initiate apoptosis of normoxic endothelial cells. These data provide a framework for the study of factors regulating endothelial cell survival and death in hypoxia.

Adenoviridae↗
PubMed1999

Suppression of glioblastoma cell growth following antisense oligonucleotide-mediated inhibition of fibroblast growth factor receptor expression.

Astrocytes exhibit significant changes in fibroblast growth factor receptor (FGFR) gene expression during malignant progression. These changes include induction of FGFR1 and concomitant loss of FGFR2 expression. The induction of FGFR1 is believed to endow malignant astrocytes with a selective growth advantage. Glioblastoma (the most malignant form of astrocytoma) cell lines, which exhibit the same pattern of FGFR gene expression as glioblastoma biopsies, were used to evaluate the contribution of FGFR1 expression to glioblastoma cell growth. Addition of phosphorothioate-modified antisense oligonucleotides complementary to the initiation site or the alpha exon of the FGFR1 gene suppressed growth of human glioblastoma-derived cell lines. Reverse antisense controls or antisense oligonucleotide complementary to FGFR2 had no effect on proliferation. Consistent with its growth-suppressive effect, FGFR1 antisense oligonucleotides markedly reduced expression of both FGFR1 mRNA and high-affinity bFGF binding sites, whereas FGFR1 reverse antisense control oligonucleotide had no effect. Antisense oligonucleotide targeted to the alpha exon of the FGFR1 gene suppressed alpha and beta alternatively spliced FGFR1 mRNA isoforms but did not alter the expression of related FGFR family members. Fluorescein-labeled antisense and reverse control oligonucleotides demonstrated cellular uptake and nuclear accumulation. These results indicate that alterations in FGFR expression may contribute to malignant proliferation in human astrocytomas. These findings also illustrate the high degree of selectivity that can be obtained with antisense oligonucleotides, a property that is essential for employing these reagents therapeutically.

Blotting, Southern↗
PubMed1999

Localization of fibroblast growth factor-2 (basic FGF) and FGF receptor-1 in adult human kidney.

BACKGROUND: The expression pattern of fibroblast growth factor-2 (FGF-2; basic FGF), a pleiotrophic growth factor, as well as one of its receptors (FGFR1), in the kidney is highly controversial. METHODS: Using an approach that combines multiple antibodies for immunohistochemistry and correlative in situ hybridization, we assessed the intrarenal expression of both FGF-2 and FGFR1 in 13 specimens of adult kidney removed during tumor nephrectomy. RESULTS: The FGF-2 expression pattern in the kidneys as detected by immunohistochemistry was variable and depended on the antibody used. The most consistent expression of FGF-2 protein was demonstrated in glomerular parietal epithelial cells, tubular cells (mainly of the distal nephron), as well as arterial endothelial cells. These locations also corresponded to areas of FGF-2 mRNA expression. Additionally, by immunohistochemistry, FGF-2 protein was detected in arterial smooth muscle cells and occasional podocytes. The expression of FGFR1 protein and mRNA was most consistently present in tubular cells of the distal nephron and in vascular smooth muscle cells. In situ hybridization, but not immunohistochemistry, also suggested FGFR1 expression in cells that could not be precisely identified within the glomerular tuft as well as some interstitial cells. CONCLUSION: These data suggest potential autocrine and paracrine pathways within the FGF-2 system, particularly within the vascular walls and in the distal nephron, and thereby provide information for further mechanistic understanding of the role of the FGF-2 system in human renal disease.

Adult↗
PubMed1999

The effect of age on medical decisions made by patients with chronic illness.

Patients are currently encouraged to appoint surrogates to make healthcare decisions for them in the event that they are not able to make those decisions for themselves. Many studies have suggested that in hypothetical situations, surrogates often make different decisions than the still-capacitated patients say they would make. Age difference between patient and appointed surrogate is one possible explanation because many surrogates are next-generation relatives. This study evaluated differences in end-of-life decision making between elderly and younger patients with chronic disease. Two age groups were interviewed: (1) geriatric patients aged 70 and older and; (2) acquired immunodeficiency syndrome (AIDS) patients aged 30-50. Subjects who demonstrated an understanding of cardiopulmonary resuscitation (CPR) and artificial nutrition and hydration (ANH) were asked to choose, on a five-point Likert scale, whether they would want these treatments for themselves in four hypothetical scenarios: (1) an older person in a coma after a car accident; (2) a younger person in a coma after a car accident; (3) an older person with Alzheimer's disease; (4) a younger person with AIDS dementia. One hundred seventy-six subjects were included: 84 geriatric patients and 92 AIDS patients. Differences in the two groups were significant only in the scenario of an older person in a coma after a car accident (p = 0.007), with the geriatric patients wanting more treatment. The lack of significant differences between healthcare decisions made by the two groups under the hypothetical scenarios utilized in this study may indicate that age differences will not prevent a next-generation healthcare agent from making substituted judgement that accurately reflects patient wishes.

Journal Article↗
PubMed1999

Feasibility of a healthcare proxy counseling program for patients with Alzheimer's disease.

BACKGROUND: Although significant progress has been made in the implementation of advance directive counseling programs for cognitively intact patients, there is a paucity of information on the outcome of these programs with patients with Alzheimer's disease. This study investigated the prevalence of completed healthcare proxies in a sample of Alzheimer's disease outpatients, and the feasibility of a systematic proxy counseling program for this population. METHODS: The setting was a geriatric psychiatry clinic. Ninety-four patients with Alzheimer's disease were surveyed for their previous completion of a healthcare proxy. All patients with capacity and without a proxy were approached to complete the advance directive with a lay counselor. RESULTS: Thirty-two percent (n = 30) of patients had completed a proxy prior to the initiation of a counseling program. Of patients without proxies (n = 64), 89% had capacity to complete one. Seventy-nine percent subsequently completed a proxy through the counseling program. Hispanics were least likely to have had a proxy prior to initiation of the program, yet were very willing to complete the document. CONCLUSIONS: The majority of patients with Alzheimer's disease in an outpatient setting did not have healthcare proxies, yet had the capacity and motivation to complete this advance directive. With physician input regarding the presence of decisional capacity, a lay counselor successfully implemented the counseling process. These results support the initiation of similar counseling programs for Alzheimer's outpatients.

Journal Article↗
PubMed1998

Evidence for involvement of Bax and p53, but not caspases, in radiation-induced cell death of cultured postnatal hippocampal neurons.

Bax (a death-promoting member of the bcl-2 gene family), the tumor suppressor gene product p53, and the ICE/ced-3-related proteases (caspases) have all been implicated in programmed cell death in a wide variety of cell types. However, their roles in radiation-induced neuronal cell death are poorly understood. In order to further elucidate the molecular mechanisms underlying radiation-induced neuronal cell death, we have examined the ability of ionizing radiation to induce cell death in primary cultured hippocampal neurons obtained from wild-type, p53-deficient and Bax-deficient newborn mice. Survival in neuronal cultures derived from wild-type mice decreased in a dose-dependent manner 24 hr after a single 10 Gy to 30 Gy dose of ionizing radiation. In contrast, neuronal survival in irradiated cultures derived from p53-deficient or Bax-deficient mice was equivalent to that observed in control, nonirradiated cultures. Western blot analyses indicated that neuronal p53 protein levels increased after irradiation in wild-type cells. However, Bax protein levels did not change, indicating that other mechanisms exist for regulating Bax activity. Adenovirus-mediated overexpression of p53 also caused neuronal cell death without increasing Bax protein levels. Irradiation resulted in a significant induction in caspase activity, as measured by increased cleavage of fluorogenic caspase substrates. However, specific inhibitors of caspase activity (zVAD-fmk, zDEVD-fmk and BAF) failed to protect postnatal hippocampal neurons from radiation-induced cell death. Staurosporine (a potent inducer of apoptosis in many cell types) effectively induced neuronal cell death in wild-type, p53-deficient and Bax-deficient hippocampal neurons, indicating that all were competent to undergo programmed cell death. These results demonstrate that both p53 and Bax are necessary for radiation-induced cell death in postnatal cultured hippocampal neurons. The fact that cell death occurred despite caspase inhibition suggests that radiation-induced neuronal cell death may occur in a caspase-independent manner.

Animals↗
PubMed1998

The medical consultant's role in caring for patients with hip fracture.

BACKGROUND: Hip fractures are an important cause of death and functional dependence in the United States. PURPOSE: To review the evidence for clinical decisions that medical consultants make for patients with hip fracture and to develop recommendations for care. DATA SOURCES: Published reports of clinical studies were found by searching MEDLINE and selected bibliographies. STUDY SELECTION: Studies were included if data were presented on clinical interventions to improve care of conditions typically encountered by medical consultants in the care of patients with hip fracture. Such conditions include timing of surgery, infection prophylaxis, thromboembolic prophylaxis, postoperative nutritional management, urinary tract management, prevention and management of delirium, application and timing of rehabilitation services, and prevention of subsequent falls. Meta-analyses; randomized, controlled trials; or other controlled studies were included if possible. If no such trials were identified, the best evidence from studies with other designs was included. DATA EXTRACTION: Interventions were selected on the basis of their efficacy or potential efficacy in improving functional outcome. Trials with positive and negative results were compared for differences in intervention and strength of study methods. DATA SYNTHESIS: Strong evidence supports medical recommendations for decisions about timing and duration of prophylactic antibiotics, selection of thromboembolic prophylaxis, urinary tract and nutritional management, and rehabilitative services. Many case series support early surgical repair, although patients who would benefit from delay and further medical work-up have not been well identified. Evidence for decisions about assessment of subsequent risk for fall and risk for and management of delirium is based largely on data from patients without hip fracture but is probably applicable. Future research should target optimal duration of thromboembolic prophylaxis, cost-effectiveness of low-molecular-weight heparin compared with that of other thromboembolic prophylactic regimens, management of delirium, rehabilitative services, and efficacy of assessment of risk for later falls. CONCLUSIONS: The data suggest that evidence-based medical care can improve hip fracture outcomes. The medical consultant has a key role in providing this care and managing the preoperative conditions and postoperative complications that may affect optimal functional recovery.

Accidental Falls↗
PubMed1998

A national survey of physician-assisted suicide and euthanasia in the United States.

BACKGROUND: Although there have been many studies of physician-assisted suicide and euthanasia in the United States, national data are lacking. METHODS: In 1996, we mailed questionnaires to a stratified probability sample of 3102 physicians in the 10 specialties in which doctors are most likely to receive requests from patients for assistance with suicide or euthanasia. We weighted the results to obtain nationally representative data. RESULTS: We received 1902 completed questionnaires (response rate, 61 percent). Eleven percent of the physicians said that under current legal constraints, there were circumstances in which they would be willing to hasten a patient's death by prescribing medication, and 7 percent said that they would provide a lethal injection; 36 percent and 24 percent, respectively, said that they would do so if it were legal. Since entering practice, 18.3 percent of the physicians (unweighted number, 320) reported having received a request from a patient for assistance with suicide and 11.1 percent (unweighted number, 196) had received a request for a lethal injection. Sixteen percent of the physicians receiving such requests (unweighted number, 42), or 3.3 percent of the entire sample, reported that they had written at least one prescription to be used to hasten death, and 4.7 percent (unweighted number, 59), said that they had administered at least one lethal injection. CONCLUSIONS: A substantial proportion of physicians in the United States report that they receive requests for physician-assisted suicide and euthanasia, and about 7 percent of those who responded to our survey have complied with such requests at least once.

Adult↗
PubMed1998

Bax involvement in p53-mediated neuronal cell death.

The tumor suppressor gene p53 has been implicated in the loss of neuronal viability, but the signaling events associated with p53-mediated cell death in cortical and hippocampal neurons are not understood. Previous work has shown that adenovirus-mediated delivery of the p53 gene causes cortical and hippocampal neuronal cell death with some features typical of apoptosis. In the present study we determined whether p53-initiated changes in neuronal viability were dependent on members of the Bcl-2 family of cell death regulators. Primary cultures of cortical neurons were derived from animals containing Bax (+/+ and +/-) or those deficient in Bax (-/-). Cell damage was assessed by direct cell counting and by measurements of MTT activity. Neurons containing at least one copy of the Bax gene were damaged severely by exposure to excitotoxins or by the induction of DNA damage. In contrast, Bax-deficient neurons (-/-) exhibited significant protection from both types of injury. Bax protein expression was elevated significantly by glutamate exposure, but not by camptothecin-induced DNA damage in wild-type neurons. The glutamate-induced increase in Bax protein was dependent on the presence of the p53 gene. However, increased p53 expression, using adenovirus-mediated transduction, was not sufficient by itself to elevate Bax protein levels. These results demonstrate that Bax is required for neuronal cell death in response to some forms of cytotoxic injury and further support the key role for p53 activation in response to excitotoxic and genotoxic injury.

Animals↗
PubMed1998

Barriers to obtaining consent in dementia research: implications for surrogate decision-making.

OBJECTIVE: To identify barriers to informed consent in research involving subjects with advanced dementia. DESIGN: A randomized controlled clinical trial of palliative care approaches, compared with usual care, in subjects with advanced dementia who are hospitalized. SETTING: A large metropolitan teaching hospital. PARTICIPANTS: All patients older than 65 years of age who have advanced dementia and a Functional Assessment Staging score of 6d to 7f and have been admitted to the hospital. MEASUREMENTS: Surrogates for all eligible subjects were approached for consent to enroll their family members in the trial. Reasons for refusal to enroll in the study were recorded and categorized as either informed refusal (i.e., the surrogate understood the research protocol but declined to give consent for participation) or as a barrier to informed consent (i.e., the surrogates could not participate in the informed consent process or there was no functional surrogate). RESULTS: Forty-nine percent of 146 eligible subjects could not be enrolled in the study. Only four surrogates refused consent for their family members. Of the remaining 68 patients, 41 eligible subjects' surrogates could not be engaged in the informed consent process, and 22 subjects did not have a functional surrogate to consent for research. CONCLUSIONS: Absence of functional surrogate decision-makers is a major barrier to research and clinical decision-making for hospitalized patients with advanced dementia.

Aged↗
PubMed1998

Pain and discomfort associated with common hospital procedures and experiences.

To determine whether reliable and valid rankings of pain and discomfort resulting from hospital procedures encountered by advanced dementia patients could be developed from interviews with cognitively intact adults, rankings of pain and discomfort resulting from 16 common procedures were obtained from two samples of hospitalized, nondemented adults using ten- (N = 100) and five- (N = 35) point numeric rating scales (NRS). Reliability was assessed by having 30 additional subjects complete ten-point NRS representing the ten most frequent procedures in a re-arranged order. By repeated measure analysis of variance, the scales discriminated between procedures (F = 35.1, P < 0.001). Subjects could discriminate between pain and discomfort (F = 21.6, P < 0.001). The five-point NRS exhibited better subject discrimination between experiences. Reliability was also acceptable. A five-point NRS produced reliable and valid pain and discomfort rankings for 16 common hospital procedures and experiences. These rankings should prove useful in reducing suffering and can serve as surrogates for quantifying pain and discomfort in dementia patients.

Adult↗