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Biomedical subjects

J Daly

Publications and source records attributed to J Daly.

At least 163 records · Page 9Linked to original sources
PubMedDate not supplied

Pro-inflammatory complement activation by the A beta peptide of Alzheimer's disease is biologically significant and can be blocked by vaccinia virus complement control protein.

The amyloid plaque is the hallmark of Alzheimer's disease (AD). The transmembrane domain and a portion of the C-terminus (A beta) of the amyloid precursor protein, are known to form the nucleus of the amyloid plaque. It has been demonstrated recently, using in vitro assays, that the A beta peptide can activate both the classical (antibody-independent) and alternate pathways of complement activation. The proposed complement activation is due to the binding of A beta to the complement components C1q and C3, respectively, which initiate formation of the proinflammatory C5a and C5b-9 membrane attack complex. In this report, we have investigated the in vitro findings for the likely complement-dependent proinflammatory properties of the Alzheimer's disease A beta peptide. We have performed experiments using congenic C5-deficient and C5-sufficient mice injected with synthetic A beta and recombinant polypeptide (C-100) containing A beta. Injection of C-100 into C5-sufficient mice induced a clear increase in the number of polymorphonuclear cells (neutrophils) at the site of injection due to complement activation and the subsequent release of proinflammatory chemtoactic factors. In sharp contrast, the C5-deficient mice did not show any increase in cellular influx. The vaccinia virus complement control protein, an inhibitor of both the classical and alternate pathway can down-regulate the biologically significant activation of complement by A beta, as demonstrated by an in vitro immunassay. The therapeutic down-regulation of A beta-caused complement activation could greatly alleviate the progression of some of the chronic neurodegeneration characteristic of Alzheimer's disease.

Alzheimer Disease↗
PubMedDate not supplied

Regional treatment of hepatic micrometastasis by adenovirus vector-mediated delivery of interleukin-2 and interleukin-12 cDNAs to the hepatic parenchyma.

We hypothesize that adenovirus (Ad) vector-mediated delivery of the human interleukin-2 (IL-2) cDNA (AdIL2) or the murine IL-12 cDNA heterodimer (AdIL12) would produce high concentrations of cytokines in the local hepatic milieu to induce host responses sufficient to inhibit the growth of experimental colon carcinoma-derived hepatic metastases. Ad vectors administered intravenously, which is a route known to deliver >90% of the vector to the hepatic parenchyma, achieved significant levels of each cytokine locally, with minimal levels in the sera. To examine the therapeutic effect, the AdIL2 and AdIL12 vectors were evaluated in a hepatic metastasis model that was established by injecting 3 x 10(4) cells from the poorly immunogenic syngeneic C26 colon carcinoma cell line into the right lobe of the livers of BALB/c mice. Animals received AdIL2, AdIL12, or control virus (10(8) plaque-forming units each) intravenously for 2 days after tumor implantation, and tumor growth was compared with naive controls. The AdNull control tumors measured 116 +/- 25 mm2 at 2 weeks. The control virus showed no significant antitumor effect. In marked contrast, both AdIL2 and AdIL12 vectors that were delivered regionally had significant antitumor effects, with AdIL2-treated animals having an average tumor size of 16 +/- 8 mm2; AdIL12-treated tumors measured 6 +/- 6 mm2 (P < .01, both compared with control). Both the AdIL2 and AdIL12 vectors provided a significant survival advantage by log-rank analysis (P < .01), but only AdIL12 translated into an increase in mean survival from 27 (naive control) to 37 days. To evaluate whether these antitumor effects were T-cell-mediated, splenocytes from AdIL2-treated, AdIL12-treated, and naive control groups were stimulated in vitro with gamma-irradiated C26 tumor cells for 5 days and tested for C26 tumor cell cytolysis by an in vitro cytotoxicity assay. Splenocytes from both AdIL2- and AdIL12-treated animals showed a dose-dependent, T-cell-mediated, specific cytolysis of CT26 cells. AdIL12 and to a lesser extent AdIL2 induced natural killer cell activity, as determined by a dose-dependent increase in lysis of the natural killer-specific target cell YAC-1. Overall, these data suggest that regional Ad-mediated delivery of IL-2 and IL-12 cDNAs may be useful for local tumor control and may warrant further investigation as a potentially useful adjuvant for the treatment of hepatic micrometastasis.

Adenoviridae↗
PubMedDate not supplied

Explaining cost variations in clinical trials using severity of illness measures.

OBJECTIVE: To determine the usefulness of severity of illness measures in explaining the variation in costs observed in economic analyses of clinical trials. METHOD: Hospital costs and three severity of illness measures (Medical Illness Severity Grouping System [MedisGroups], Acute Physiology and Chronic Health Evaluation [APACHE] II, APACHE III) were calculated for patients undergoing surgical management of gastrointestinal malignancies. Regression models were developed to determine the predictive ability of the severity of illness measures on total costs and length of stay of surgical patients. RESULTS: There was not a significant reduction in the cost variance among patients after correcting for severity with use of the MedisGroups score. APACHE II scores were a better predictor of total costs, although this relationship did not reach statistical significance. As a continuous variable, APACHE III scores explained $326 of extra cost for each point on the scale, and as a categorical variable, identified those patients who were most expensive to care for and with long lengths of stay. CONCLUSION: Neither MedisGroups nor APACHE II were found to be useful in explaining cost variations in a clinical trial. The APACHE III system was more useful in discriminating resource intensive patients.

Clinical Trials as Topic↗
PubMedDate not supplied

The experience of hope for survivors of acute myocardial infarction (AMI): a qualitative research study.

This qualitative study was undertaken to explore the relevance and meaning of the experience of hope for survivors of acute myocardial infarction (AMI). Depth interviews were conducted with eight survivors (n = 8) of AMI at four weeks following discharge from hospital. Analysis of transcribed interviews revealed three distinct narrative themes. These were holding on to human connectedness, finding and harnessing the 'will' to live, and, having faith in the primacy of a higher power. Study findings are discussed in relation to the literature. Findings of the study assist in building knowledge and understanding of the complex phenomenon of hope. Implications for nursing practice and research are drawn from study findings.

Aged↗
PubMedDate not supplied

Physician use of and attitudes regarding the minimum data set.

OBJECTIVE: To determine physician use of the Minimum Data Set (MDS), part of the Resident Assessment Instrument (RAI). DESIGN: A population-based survey. SETTING: The United States. PARTICIPANTS: A total of 2223 physicians listing geriatrics as their primary specialty, 1921 of whom are internists and 302 family physicians. MEASUREMENTS: A 34-item questionnaire asking nine physician-specific demographic questions; nursing home caseload; percent time spent reviewing MDS and care plan; how the information on the MDS was used. Physicians were also asked to describe their attitudes about the MDS. RESULTS: Among the 472 physicians who completed the survey and cared for nursing home patients, 357 were internists and 107 were family physicians. Ninety-one percent of the physicians were board certified, 76% had certificate of added qualifications in geriatrics,65% oversaw 20 nursing home patients. Only 11% of physicians reported reviewing the entire MDS, and 21% part of the MDS for all of their patients. Nineteen percent of physicians did not review the care plan for any of their patients. Fifty-six percent of 461 comments made by physicians regarding the MDS were negative or derogatory. CONCLUSIONS: Many practicing geriatricians are not using MDS to facilitate medical decisions. If this physician population is not using the MDS, there is a need to improve the information transfer from the MDS form to the busy clinician.

Journal Article↗