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Biomedical subjects

D P Murphy

Publications and source records attributed to D P Murphy.

At least 37 records · Page 2Linked to original sources

The illusion of end-of-life resource savings with advance directives. SUPPORT Investigators. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatment.

OBJECTIVE: Would increasing the documentation of advance directives (ADs) lead to a reduction in resource utilization? We examined this question by conducting three secondary analyses: (1) we tested for a change in resource use among those who died in the hospital at a time before and after an intervention that increased the documentation of ADs in the medical record; (2) we replicated analyses of published studies that reported an association of chart documentation of ADs and hospital resource use; and (3) we examined whether a potential explanation of the observed association is biased documentation of ADs among patients who have completed an AD. DESIGN: Replication of analysis of previous published studies using data from a prospective cohort study and block-randomized controlled trial. SETTING: Five teaching hospitals in the United States. PATIENTS: A total of 9105 seriously ill patients were enrolled in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT), including 4301 patients in the 2 years (1989-91) before the Patient Self-Determination Act (PSDA) and 4804 in the 2 years (1992-94) after the PSDA implementation, with 2652 patients receiving the intervention and 2152 serving as controls. INTERVENTIONS: The SUPPORT intervention provided a nurse to facilitate communication among patients, surrogates, and physicians about preferences for and outcomes of treatments. Documenting existing advance directives was also one of this nurse's tasks. The Patient Self-Determination Act required that health care institutions inquire about and document existing advance directives at the time of hospital admission. MEASUREMENT: Hospital resource use was derived from the Therapeutic Intensity Scoring System and hospital length of stay, converted into 1994 dollars. RESULTS: Chart documentation of existing advance directives at the time of study admission increased with both the PSDA and the SUPPORT intervention. We found that intervention patients were more likely to have pre-existing ADs documented. Despite this increase, there was no corresponding change in hospital resource use for those who died during the enrollment hospitalization. Replication of analyses from published studies using data from the block randomized controlled trial found that ADs documented by the third day of serious illness were associated with a 23% reduction in hospital resource use among control patients ($21,284 with ADs documented compared with $26,127 without, 95% CI 1-48% reduction). However, this association was not observed among intervention patients, who had more pre-existing ADs documented in the medical record. Intervention patients with early documentation of ADs showed a trend toward greater cost ($28,017 compared with $24,178 among those without AD documentation, 95% CI 0-25% increase). The rate of documentation and characteristics of those with documentation differed between control and intervention patients. Intervention patients were more likely (as reported by patient or surrogate interview) to have ADs documented in the medical record by the third day (55% vs 32%, P < .001). In contrast to intervention patients, control patients who were older, less wealthy, less educated, more likely to prefer to forgo CPR, and more likely to want life-sustaining treatment limited had their ADs documented. These associations were not found among intervention patients when comparison was made between those with and those without an AD documented in the medical record. CONCLUSION: Increasing the documentation of pre-existing ADs was not associated with a reduction in hospital resource use. ADs documented without further intervention by the third day of a serious illness were associated with decreased hospital resource use. However, we did not find this association with an intervention that increased AD documentation. One potential explanation of these findings is that classification of those with an AD was based on cha

Advance Directives↗

Liesegang rings.

Explore the source record for details and available documents.

Chemical Precipitation↗

Fibroblast growth factor-2 protects entorhinal layer II glutamatergic neurons from axotomy-induced death.

The entorhinal cortex is a major relay between the hippocampus and other cortical and subcortical regions. Glutamatergic axons from layer II neurons form the entorhinal cortical projection to the hippocampus via the perforant pathway. We have demonstrated previously that lesion of the perforant pathway causes the death of approximately 30% of entorhinal layer II (ECL2) neurons. To elucidate mechanisms contributing to neuronal death and to investigate strategies preventing it, we identified the phenotype of the vulnerable neuronal population. Sections were immunolabeled with antibodies to the neuronal markers NeuN, glutamate, and calbindin-D28k, and to receptors for fibroblast growth factor-2 (FGFR1) and NMDA (NMDAR1) and were examined using confocal microscopy. Calbindin immunoreactivity was strikingly lamina-specific to ECL2, where one-third of all ECL2 neurons were calbindin-positive. Localization of glutamate revealed that half of the glutamatergic ECL2 neurons coexpressed calbindin. Quantification using unbiased stereology at 9 weeks after lesion of the perforant pathway revealed that the only ECL2 neuronal population that experienced a significant (70%) loss (20% of the total) was the population of glutamatergic ECL2 neurons that did not coexpress calbindin. All ECL2 neurons expressed FGFR1; therefore, we tested the role of FGF-2 in the survival of glutamatergic ECL2 neurons. We grafted fibroblasts genetically engineered to express nerve growth factor or FGF-2 and found that only FGF-2 grafts prevented loss of the vulnerable glutamatergic/calbindin-negative neurons. We present a hypothesis for the selective vulnerability of these glutamatergic/calbindin-negative ECL2 neurons and address the role of FGF-2 in neuronal rescue.

Afferent Pathways↗

Mycotic aneurysm of the thoracic aorta caused by Clostridium septicum.

We describe a case-of a 78-year-old man who presented with a mycotic aneurysm of the thoracic aorta caused by Clostridium septicum and underwent successful resection. There are only 3 cases of mycotic aneurysms caused by Clostridium septicum reported in the literature. Clostridium septicum infections have been shown to have a high association with gastrointestinal and hematologic malignancies. All patients with Clostridium septicum infections, therefore, require a search for gastrointestinal lesions, as they may represent a source of persistent bacteremia. This patient had no malignant lesions but did have multiple benign sigmoid polyps.

Aged↗

Decline in creatinine clearance in a patient with glomerulomegaly associated with a congenital cyanotic heart disease.

Glomerulomegaly is associated with congenital cyanotic heart disease and has heretofore been considered a benign condition. We describe a patient with congenital cyanotic heart disease and glomerulomegaly. Deterioration of renal function was demonstrated by comparison of creatinine clearances measured at the time of kidney biopsy and 4 years later. No alteration in kidney histology other than glomerulomegaly and focal glomerulosclerosis at autopsy could account for this deterioration. This is the first description of deterioration of renal function in a patient with glomerulomegaly and congenital cyanotic heart disease. This observation may influence the management of patients with glomerulomegaly and congenital cyanotic heart disease who are potential recipients of heart or heart-lung allografts.

Adult↗

Synergistic effects of epidermal growth factor (EGF) and insulin-like growth factor I/somatomedin C (IGF-I) on keratinocyte proliferation may be mediated by IGF-I transmodulation of the EGF receptor.

The epidermal growth factor (EGF) receptor pathway is an important mediator of keratinocyte growth in vitro and both receptor and ligand components of this pathway are abnormally expressed in hyperproliferative epidermis. The purpose of this study was to examine interactions between the EGF receptor pathway and the insulin-like growth factor I/somatomedin C (IGF-I) receptor pathway in modulating the growth of cultured normal human keratinocytes. Short-term growth of keratinocytes in a chemically defined medium demonstrated that neither EGF nor IGF-I alone could support significant keratinocyte spreading or proliferation, but that a combination of EGF with IGF-I or high-dose insulin could. IGF-I or high-dose insulin transmodulates keratinocyte EGF receptor expression via the IGF-I receptor in a dose- and time-dependent manner, increasing EGF receptor binding an average of 1.8 times up to a maximum of fourfold without altering EGF binding affinity. Staining of normal human epidermis with an IGF-I receptor specific monoclonal antibody demonstrates that IGF-I receptors localize to the basal proliferative cell compartment, suggesting that IGF-I receptor and EGF receptor pathway interactions may play a role in the regulation of epidermal growth and in the pathogenesis of hyperproliferative skin diseases.

Cell Division↗

Increased dermal expression of platelet-derived growth factor receptors in growth-activated skin wounds and psoriasis.

Platelet-derived growth factor (PDGF) is a potent mitogenic and chemotactic factor for fibroblasts and other cell types. PDGF effects are mediated by binding of PDGF to dimeric PDGF receptors possessing intrinsic tyrosine kinase activity. We examined the expression pattern of PDGF receptors in cryostat sections of normal and growth-activated human skin using a monoclonal antibody, PR7212, specific for the beta subunit of the PDGF receptor. PDGF receptors were expressed at low levels in normal skin, with only occasional staining of dermal connective tissue cells. In contrast, PDGF receptor expression was greatly elevated in the dermis of growth-activated skin from 15 chronic wounds and 10 psoriatic lesions. PDGF receptors were increased in dermal fibroblasts and in dermal blood vessels in both conditions. Immunoblot analysis confirmed the increased expression of beta-subtype PDGF receptors in psoriatic lesional tissue. PDGF receptors were not detected in normal or growth-activated epidermis. Differential expression of PDGF receptors could regulate increased proliferation of vascular and connective tissue cells observed in psoriasis and chronic wounds.

Antibodies, Monoclonal↗

Principles of oncology: how radiation therapy works.

Radiation therapy remains the primary mode of treatment for many types and stages of cancer as well as playing an extremely important adjunct role in the treatment of many other malignancies, often in combination with medical and surgical oncology. The combination treatments often yield cure and long-term control rates far in excess of single modality treatment.

Humans↗

A study comparing the immunologic responses of swine to pseudorabies viral antigens based on the ELISA, serum virus neutralization, and latex agglutination tests.

A study of pseudorabies virus (PRV)-vaccinated pigs comparing the immune responses detected by the latex agglutination test (LAT) with responses detected by other routine tests for pseudorabies antibodies indicated that LAT was more sensitive than either the enzyme-linked immunosorbent assay (ELISA) or the serum virus neutralization test (SVNT). The LAT detected antibodies sooner than ELISA and SVNT in unvaccinated pigs after challenge with virulent PRV. The specificities of the 3 tests were found to be near 100%. The LAT is a good alternative to SVNT or ELISA for detection of PRV-specific antibodies.

Animals↗

Survival of pseudorabies virus in aerosol.

The survival of pseudorabies virus in an aerosol was studied under different environmental conditions of temperature and relative humidity. Pseudorabies virus decayed logarithmically with mean half-lives of 17.4 (85% relative humidity, 22 C), 18.8 (25% relative humidity, 22 C), 27.3 (85% relative humidity, 4 C), 36.1 (55% relative humidity, 22 C), and 43.6 (55% relative humidity, 4 C) minutes. Virus survival was significantly improved in environments at 55% relative humidity, compared with those at 85% relative humidity (P = 0.017). Rates of survival were improved in environment at 4 C in comparison with those at 22 C. Results suggest that, under the best conditions of this study, the infectivity of pseudorabies virus in an aerosol decreases by 50% in less than 1 hour.

Aerosols↗

Pseudorabies virus latency and reactivation in vaccinated swine.

Latency and reactivation of pseudorabies virus in swine was studied. Thirty-one pigs were assigned to 5 groups and were given 1 of 4 vaccines; 10 remained unvaccinated controls. All pigs were then challenge exposed with a sublethal dose of virulent pseudorabies virus. One hundred one days after challenge exposure, all pigs were treated with dexamethasone to reactivate the virus. Virus-positive tonsil and nasal mucus isolates were recovered from 29 of the 31 pigs over a 12-day period. Frequency and duration of virus-positivity were significantly (P less than 0.05) and consistently lower among vaccinated pigs than among the unvaccinated controls. It was concluded that vaccination before challenge exposure had little or no effect on the rate of establishment of virus latency, but that vaccination reduced shedding after subsequent reactivation of the virus.

Animals↗

Interleukin 6 is expressed in high levels in psoriatic skin and stimulates proliferation of cultured human keratinocytes.

Psoriasis is a common papulosquamous skin disease. The histopathology is characterized by epidermal hyperplasia and inflammation. Recent studies suggest that keratinocyte proliferation and inflammation in psoriasis are manifestations of the same underlying pathological process. Interleukin 6 (IL-6), a cytokine that is a major mediator of the host response to tissue injury and infection, is produced by both keratinocytes and leukocytes in culture. IL-6 expression was studied in psoriatic plaques by immunoperoxidase staining with two different polyclonal anti-recombinant IL-6 antisera and by in situ nucleic acid hybridization with IL-6 cRNA probes. Epidermal and dermal cells in active psoriatic plaques from 35 psoriasis patients stained heavily for IL-6 as compared with nonlesional skin and with plaques after treatment with antimetabolic and antiinflammatory agents. Absorption of the anti-recombinant IL-6 antisera with purified fibroblast-derived IL-6 or with recombinant IL-6, but not bovine serum albumin, removed the immunostaining. Increased levels of IL-6 were detected in the plasma of patients with active psoriasis (mean 3 ng/ml) by using two different bioassays. IL-6 production by proliferating keratinocytes was suggested by IL-6-specific immunostaining in cultured normal and psoriatic keratinocytes and by the detection of mRNA specific for IL-6 in psoriatic epidermis by in situ hybridization. IL-6 stimulated the proliferation of cultured, normal human keratinocytes as assessed by two different assays. Thus, IL-6 could directly contribute to the epidermal hyperplasia seen in psoriatic epithelium as well as affect the function of dermal inflammatory cells.

Cell Division↗

Influence of temperature and age on the recovery of pseudorabies virus from houseflies (Musca domestica).

In laboratory experiments, pseudorabies virus was readily recovered from within the body of houseflies (Musca domestica L) that had ingested the virus. Age of the fly and ambient temperature affected the rate of virus inactivation within the houseflies. Virus half-life in 3-day-old flies was 6.36 hours vs 2.81 hours in flies 8 or 13 days old. Half-life in 5-day-old flies was 12.92 hours at 10 C, 5.95 hours at 20 C, and 2.69 hours at 30 C. Virus half-life in dead flies was 9.06 hours at 10 C, 4.28 hours at 20 C, and 1.71 hours at 30 C. The data did not provide any evidence of virus replication in either living or dead flies.

Aging↗

Carbamazepine vs lithium in the treatment and prophylaxis of mania.

Fifty-four acutely manic patients were allocated to treatment on a double-blind basis with either carbamazepine or lithium carbonate. The short-term effects of treatment were studied over a period of six weeks and the longer term, prophylactic, effects over a period of up to a year. Additional 'rescue' medication was allowed when clinically indicated. There was a high drop-out rate from the trial. Despite this, it appeared that valid comparisons between the two treatments could be made. No statistically significant differences were found, but carbamazepine appeared slightly less effective as a treatment for acute mania and more effective as a prophylactic treatment in this group of patients. Possible predictors of individual responsiveness to each treatment are discussed.

Adolescent↗

Morphometric study of hepatic ultrastructure in alcoholic hepatitis. Veterans Administration Cooperative Study Group on Alcoholic Hepatitis.

We undertook a morphometric analysis of hepatocellular organelles in an attempt to correlate their changes with the clinical stages of patients with alcoholic hepatitis. Although hepatic ultrastructural alterations did not correlate with disease severity, we found significant differences between patient and control groups in the measured parameters of non-organelle cytoplasm, mitochondria, SER, RER, glycogen, and lipid.

Biopsy↗