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Biomedical subjects

D Burns

Publications and source records attributed to D Burns.

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

Evaluation of electrochemiluminescent technology for inhibitors of granulocyte colony-stimulating factor receptor binding.

An electrochemiluminescent (ECL) assay was developed to identify compounds that inhibit the interaction of granulocyte colony-stimulating factor (GCSF) with its recombinant human receptor. The ECL technology uses a tris-(bipyridine) chelate of ruthenium, which, in the presence of excess tripropylamine, undergoes a redox reaction cycle to produce light. Paramagnetic beads with primary antibody were coated with secondary anti-GCSF receptor antibody, which were then bound with GCSF receptor. These samples were incubated with ruthenylated GCSF in the presence and absence of test compounds. The bead density, receptor and ligand concentrations, and incubation time were optimized in the assay. A set of mixed compound plates was screened to examine the feasibility of using this technology in high throughput screening. The results from this format were found to be comparable to the assay performed using a time-resolved fluorescence format.

Coloring Agents↗
PubMed1999

The relative value of CD4 cell count and quantitative HIV-1 RNA in predicting survival in HIV-1-infected women: results of the women's interagency HIV study.

OBJECTIVES: To determine factors associated with survival and to assess the relative strength of CD4 cell count and HIV-1 RNA in predicting survival in a cohort of HIV-1-infected women. DESIGN: Prospective cohort, enrolled during 1994-1995, with median follow-up of 29 months RESULTS: Of 1769 HIV-infected women 252 died. In multivariate analyses, lower CD4 cell count, higher quantitative plasma HIV-1 RNA, and the presence of a self-reported AIDS-defining (Class C) condition were significantly associated with shorter survival: the relative hazard (RH) of dying was 1.17, 3.27, and 8.46, respectively for women with baseline CD4 cell count of 200-349, 50-199, and < 50 x 10(6) cells/l, compared with women with CD4 cell count of > or = 350 x 10(6) cells/l. Compared with women with HIV-1 RNA levels of < 4000 copies/ml plasma, the RH of dying for women with baseline quantitative HIV-1 RNA measurements of 4000-20,000, 20,000-100,000, 100,000-500,000 and > 500,000 copies/ml, was 2.19, 2.17, 3.16, and 7.25, respectively. CD4 cell count had as strong a prognostic value as HIV-1 RNA level, particularly among participants with more advanced immunodeficiency. When the analysis was adjusted to eliminate the distortion created by having disproportionately sized strata of the categorized variables, the relative hazard of death associated with CD4 cell count became even larger in comparison with that for HIV-1 RNA. Eliminating from the analysis all follow-up time during which participants could have received highly active antiretroviral therapy did not change these findings. Age was not a predictor of survival after adjustment for covariates. CONCLUSIONS: CD4 cell count and HIV-1 RNA had similar prognostic value in this cohort of HIV-1-infected women. Even in the presence of a low viral burden, a substantially decreased CD4 cell count remained a strong predictor of mortality.

CD4 Lymphocyte Count↗
PubMed1999

Prevalence and predictors of squamous cell abnormalities in Papanicolaou smears from women infected with HIV-1. Women's Interagency HIV Study Group.

BACKGROUND: Cervical neoplasia occurs with increased frequency among women infected with HIV-1. OBJECTIVE: To characterize prevalence of and risk factors for abnormal cervical cytology among women with HIV and to compare them to uninfected women. METHODS: Baseline cervical cytology was obtained from 1713 women seropositive for HIV and 482 at-risk control women who were enrolled in the Women's Interagency HIV Study, a multicenter prospective cohort study conducted in six U.S. cities. Associations with sociodemographic, medical, and sexual variables were assessed by Fisher's exact test, Mantel extension test, and logistic regression analysis. RESULTS: Cervical cytology was abnormal in 38.3% of HIV-infected women (atypical squamous cells of uncertain significance [ASCUS] 20.9%, low-grade squamous cells of uncertain significance [LSIL] 14.9%, high-grade squamous cells of uncertain significance [HSIL] 2.3%, cancer 0.2%) and 16.2% of HIV-uninfected women (ASCUS 12.7%, LSIL 2.3%, HSIL 1.2%, cancer 0.0%). Risk factors for any abnormal cytology in multivariate analysis included HIV infection, CD4 cell count, HIV RNA level, detection of human papillomavirus (HPV), a prior history of abnormal cytology, employment, and number of male sex partners within 6 months of enrollment. Prior abortion was associated with a decreased risk of cytologic abnormality. CONCLUSIONS: Cervical cytologic abnormalities were frequent among women infected with HIV, although high-grade changes were found in only 2.5%. Factors linked to sexual and reproductive history, HPV infection, and HIV disease all influenced risk.

Adult↗
PubMed1999

Lower genital tract infections among HIV-infected and high-risk uninfected women: findings of the Women's Interagency HIV Study (WIHS).

BACKGROUND AND OBJECTIVES: Few comparisons of factors associated with sexually transmitted diseases (STDs) and HIV are available for representative samples of American women. GOAL OF THE STUDY: To compare factors associated with STDs in a large sample of women infected with HIV and women not infected with HIV. STUDY DESIGN: A cross-sectional analysis of STDs in 2,058 women seropositive (HIV+) for HIV and 567 women seronegative (HIV-) for HIV. RESULTS: HIV + women were more likely than HIV- women to report previous STDs, with the exceptions of chlamydia and bacterial vaginosis. Both HIV status and CD4 lymphocyte count were associated with evidence of genital ulcerations, warts, and vaginal candidiasis (p <0.001 for all). HIV- women were more apt to report recent vaginal intercourse (p <0.001), a factor that was independently associated with the occurrence of bacterial and protozoan infections. CD4 lymphocyte depletion was the factor most closely associated with the expression of chronic viral infections. CONCLUSIONS: In this North American cohort, HIV+ women were more likely than HIV- women to report previous genital tract infections and symptoms. However, the HIV+ women reported less recent sexual activity and few gonococcal or chlamydial infections.

Adolescent↗
PubMed1999

St. Louis encephalitis and the substantia nigra: MR imaging evaluation.

Neuroimaging findings in cases of St. Louis encephalitis (StLE) have yet to be reported despite the relatively high frequency of this entity. An epidemic permitted the documentation of isolated hyperintensity of the substantia nigra on T2-weighted images in two patients with StLE. This distribution of MR imaging abnormality in cases of StLE mirrors the reports presented in the literature that implicate the substantia nigra as peculiarly susceptible to the StLE virus. Isolated lesions of the substantia nigra revealed by T2-weighted imaging should suggest the possibility of StLE.

Adult↗
PubMed1998

Autosomal genomic scan for loci linked to obesity and energy metabolism in Pima Indians.

An autosomal genomic scan to search for linkage to obesity and energy metabolism was completed in Pima Indians, a population prone to obesity. Obesity was assessed by percent body fat (by hydrodensitometry) and fat distribution (the ratio of waist circumference to thigh circumference). Energy metabolism was measured in a respiratory chamber as 24-h metabolic rate, sleeping metabolic rate, and 24-h respiratory quotient (24RQ), an indicator of the ratio of carbohydrate oxidation to fat oxidation. Five hundred sixteen microsatellite markers with a median spacing of 6.4 cM were analyzed, in 362 siblings who had measurements of body composition and in 220 siblings who had measurements of energy metabolism. These comprised 451 sib pairs in 127 nuclear families, for linkage analysis to obesity, and 236 sib pairs in 82 nuclear families, for linkage analysis to energy metabolism. Pointwise and multipoint methods for regression of sib-pair differences in identity by descent, as well as a sibling-based variance-components method, were used to detect linkage. LOD scores >=2 were found at 11q21-q22, for percent body fat (LOD=2.1; P=.001), at 11q23-q24, for 24-h energy expenditure (LOD=2.0; P=.001), and at 1p31-p21 (LOD=2.0) and 20q11.2 (LOD=3.0; P=.0001), for 24RQ, by pointwise and multipoint analyses. With the variance-components method, the highest LOD score (LOD=2.3 P=.0006) was found at 18q21, for percent body fat, and at 1p31-p21 (LOD=2.8; P=.0003), for 24RQ. Possible candidate genes include LEPR (leptin receptor), at 1p31, and ASIP (agouti-signaling protein), at 20q11.2.

Chromosome Mapping↗
PubMed1998

Introducing quality assurance to health service delivery--some approaches from South Africa, Ghana and Kenya.

The following report combines the contributions of four health care professionals engaged in quality improvement activities in three different areas of Africa--Ghana in West Africa, Kenya in the East, and the Republic of South Africa. These reports provide current and vivid accounts of the impact of quality assurance and quality improvement activities on areas of change in each country's rapidly expanding health care system.

Delivery of Health Care↗
PubMed1998

Discordant epicardial and microvascular endothelial responses in heart transplant recipients early after transplantation.

BACKGROUND: Cardiac allograft vasculopathy represents the leading cause of death in heart transplant recipients who survive more than 1 year. Functional endothelial abnormalities are sensitive measures of the early development of cardiac allograft vasculopathy, but the relative importance of large and small coronary vessel abnormalities has not been evaluated. The purpose of the study was to distinguish between large and small coronary endothelial dysfunction in patients early after heart transplantation and to test the hypothesis that microvascular endothelial responses can be preserved in the presence of epicardial endothelial dysfunction. METHODS: Changes in epicardial lumen area and coronary artery blood flow in response to intracoronary administration of adenosine, acetylcholine, and nitroglycerin were measured simultaneously by use of an intravascular ultrasound catheter positioned over a Doppler flow wire in the left anterior descending coronary artery. The combination of these techniques allowed distinction between large and small coronary vascular responses. In 19 patients studied early after transplantation, adenosine (16 and 32 microg), acetylcholine (5.4 and 54 microg), and nitroglycerin (200 microg) were infused, with continuous intravascular ultrasound imaging and Doppler velocity measurements. RESULTS: Acetylcholine induced paradoxical epicardial vasoconstriction in 12 of 19 patients (73% +/- 6% of baseline); vasodilation occurred in 7 (108% +/- 3%). In spite of this constriction, coronary artery flow increased in all 19 patients, to the same extent in patients with constriction and those with dilation (239 +/- 26 vs 193 +/- 20, p = 0.38). Adenosine and nitroglycerin increased area (107% +/- 1% and 112% +/- 3%) and flow (258% +/- 17% and 197% +/- 11%) in all patients. None of the area or flow responses correlated with the degree of intimal thickening. CONCLUSIONS: Acetylcholine increased coronary artery flow early after transplantation, indicating preserved microvascular responses in spite of epicardial vasoconstriction. Simultaneous measurement of area and velocity responses, by permitting evaluation of the relative contribution of epicardial and microvascular vessels, may offer unique insights into coronary endothelial function.

Acetylcholine↗
PubMed1997

alpha-MSH modulates local and circulating tumor necrosis factor-alpha in experimental brain inflammation.

Tumor necrosis factor (TNF-alpha) underlies pathological processes and functional disturbances in acute and chronic neurological disease and injury. The neuroimmunomodulatory peptide alpha-MSH modulates actions and production of proinflammatory cytokines including TNF-alpha, but there is no prior evidence that it alters TNF-alpha induced within the brain. To test for this potential influence of the peptide, TNF-alpha was induced centrally by local injection of bacterial lipopolysaccharide (LPS). alpha-MSH given once i.c.v. with LPS challenge, twice daily intraperitoneally (i.p.) for 5 d between central LPS injections, or both i.p. and centrally, inhibited production of TNF-alpha within brain tissue. Inhibition of TNF-alpha protein formation by alpha-MSH was confirmed by inhibition of TNF-alpha mRNA. Plasma TNF-alpha concentration was elevated markedly after central LPS, indicative of an augmented peripheral host response induced by the CNS signal. The increase was inhibited by alpha-MSH treatments, in relation to inhibition of central TNF-alpha. Presence within normal mouse brain of mRNA for the alpha-MSH receptor MC-1 suggests that the inhibitory effects of alpha-MSH on brain and plasma TNF-alpha might be mediated by this receptor subtype. The inhibitory effect of alpha-MSH on brain TNF-alpha did not depend on circulating factors because the effect also occurred in brain tissue in vitro. This indicates that alpha-MSH can act directly on brain cells to inhibit their production of TNF-alpha. If central TNF-alpha contributes to pathology in CNS disease and injury, and promotes inflammation in the periphery, agents that act on brain alpha-MSH receptors should decrease the pathological TNF-alpha reaction and promote tissue survival.

Animals↗
PubMed1997

Changes in total, CD4+, and CD8+ lymphocytes during pregnancy and 1 year postpartum in human immunodeficiency virus-infected women. The Women and Infants Transmission Study.

OBJECTIVE: To assess changes in lymphocyte subsets during pregnancy and 1 year postpartum in human immunodeficiency virus (HIV)-infected women. METHODS: Changes in CD4+ and CD8+ cell counts, CD4 and CD8 percent, CD4/CD8 ratio, and total lymphocyte count and percent were assessed in each of 226 HIV-infected women followed during pregnancy and 1 year postpartum, and for each of 100 nonpregnant HIV-infected woman during 1 year. Trends over time were compared between pregnant women with and without several covariates. Postpartum changes over a 1-year period were compared to a 1-year period in the nonpregnant cohort. RESULTS: There was a mean increase of 2.76 per week in the CD4+ cell count during pregnancy (P = .04). No other characteristics changed significantly during pregnancy. The mean CD4+ and CD8+ cell counts, the CD8 percent, and the total lymphocyte count and percent increased immediately postdelivery. During the first postpartum year, there were statistically significant declines in the absolute CD4+ and CD8+ cell counts, the relative CD4 and CD8 percentages, and the total lymphocyte count and percentage. The rate of change for CD4+ and CD8+ counts, but not for CD4 percent, was less during 1 year in the nonpregnant cohort than in the first postpartum year, and the CD8 percent increased in the nonpregnant women. A wide variability in trends of all measurements during pregnancy was seen. CONCLUSION: During pregnancy, CD4 and CD8 percentages remain stable. There are no clinically significant changes during pregnancy or postpartum in any lymphocyte parameter we assessed. Postpartum changes in lymphocytes and lymphocyte subsets most likely represent a return to baseline from the physiologic changes of pregnancy and the immediate postpartum period.

Adult↗
PubMed1997

Testing a community level research utilization intervention.

Research supports changing practice from heparinized to saline flushes for adults, yet heparin continues to be used in clinical practice. The primary aim of this study was to test the effectiveness of a community level innovation diffusion intervention as a method of stimulating research utilization at three acute care facilities in one community simultaneously. The change advocated was the flushing of intermittent intravenous devices (IID) with saline rather than heparin. Pilot IID units were chosen on which to test the change from the use of heparin to saline flushes. The innovation focused on staff empowerment and was implemented in five phases. The change to saline flushes was successful and has been maintained.

Adult↗
PubMed1997

An Eastern Cooperative Oncology Group phase I trial of all-trans-retinoic acid and interferon-alpha: E2Y92.

The Eastern Cooperative Oncology Group conducted a Phase I trial to determine the maximally tolerated doses of combination therapy with alpha interferon (IFN-alpha) and all-trans-retinoic acid (tRA). Fifty patients with incurable malignancies received IFN-alpha administered subcutaneously three times weekly, and tRA administered by mouth at bedtime. Doses were escalated between patient groups, starting at tRA dose level of 45 mg/m2 and 3 million units of IFN-alpha. Major, dose-limiting toxicities were attributable to either the tRA (rash, chelitis) or IFN (constitutional symptoms), and were observed only at tRA dose levels of 224 mg/m2 and 291 mg/m2, or 6 million units of IFN-alpha. The maximally tolerated dose level of 172.5 mg/m2 of tRA and 3 million units of IFN-alpha was well-tolerated, with no grade 3 or 4 toxicities attributable to therapy. One patient at the third dose level (75 mg/m2 of tRA and 3 million units of IFN-alpha) developed acute hepatic and renal failure and a metabolic encephalopathy of unclear etiology. We conclude that tRA and IFN-alpha may be safely administered together at the maximally tolerated dose of tRA as a single agent without unexpected side effects. The recommended doses of IFN-alpha and tRA for Phase II trials are 3 million units of IFN-alpha and 172.5 mg/m2 of tRA.

Adult↗
PubMed1997

Maternal immunologic and virologic risk factors for infant human immunodeficiency virus type 1 infection: findings from the Women and Infants Transmission Study.

Maternal virus load of human immunodeficiency virus 1 (HIV-1) and maternal immunity are both associated with risk of an infected infant. The interrelationship of these two variables in describing that risk was assessed in a multisite study of 475 mother-infant pairs. Infant infection was associated with low CD4 cell percentage, high CD8, CD8/CD38, and CD8/DR cell percentages, persistently positive HIV-1 cultures, and high HIV-1 titer (P < .001, .001, .005, .006, .001, and .013, respectively). The association of CD4 cell percentage and increased CD8, CD8/CD38, and CD8/DR cell percentages with transmission was restricted to the 42% of women whose HIV-1 cultures were not persistently positive (all P < .001). Women with at least 1 negative culture and high CD4 cell percentage or low CD8 cell percentage were at very low risk (0-4%) of transmitting HIV-1, while those with always positive cultures transmitted at a high rate (18%-27%), regardless of immune status.

Adolescent↗
PubMed1997

Carotid plaque morphology and clinical events.

BACKGROUND AND PURPOSE: Studies have suggested that B-mode ultrasonography can be used to determine carotid plaque composition and that specific plaque characteristics are associated with a worse clinical outcome. However, histological studies examining the relationship between carotid plaque morphology and clinical outcome have reported conflicting findings. Furthermore, few investigators have described plaque morphology in quantifiable terms. This study examines the association between the volume of carotid plaque constituents and preoperative ischemic neurological symptoms. Constituents examined were chosen based on their potential for identification by current diagnostic imaging modalities such as ultrasound or MRI. METHODS: Atherosclerotic plaques from 43 patients undergoing carotid endarterectomy were examined histologically, with sections obtained every 0.5 to 1 mm. The lesions were examined for the presence and quantity of fibrous intimal tissue, intraplaque hemorrhage, lipid core, necrotic plaque core, and calcification. The quantity of each constituent was compared in plaques removed from symptomatic patients with those excised from asymptomatic individuals. Differences were analyzed with a Kolmogorov-Smirnov statistic. RESULTS: There was no difference between plaques removed from asymptomatic and symptomatic patients with regard to the presence and volume of fibrous intimal tissue, intraplaque hemorrhage, the lipid core, the necrotic core, or calcification. CONCLUSIONS: In patients with highly stenotic carotid lesions who are undergoing carotid endarterectomy, gross plaque composition is similar regardless of preoperative symptom status. Given this similarity, it is unlikely that differences in the volume of intraplaque hemorrhage, lipid core, necrotic core, or calcification in atherosclerotic carotid plaques explain their embolic history.

Aged↗