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Biomedical subjects

E Barron

Publications and source records attributed to E Barron.

At least 19 recordsLinked to original sources
PubMed2006

Palliation for suspected unresectable hilar cholangiocarcinoma.

AIM: The aim of this study was to evaluate the outcome of different techniques of palliation for patients with hilar cholangiocarcinoma. METHOD: All patients treated with palliative intent between 1988 and 2004 at the Royal Infirmary of Edinburgh were reviewed. Patients were analysed on an intention to treat basis. Demographics, procedure and outcome (including re-admissions) were recorded. RESULTS: Two hundred and thirty-three patients underwent palliative treatment for suspected hilar cholangiocarcinoma. The diagnosis was confirmed histologically in 109 patients. The procedure related morbidity and mortality was 54/225 and 18/207 respectively. Seventy-one patients required re-admission. Twenty patients underwent surgical biliary bypass for jaundice. Those undergoing surgical palliation had a longer median (95% CI) time to re-admission (16 (0-36) vs.7 (2-12) weeks, p=0.001). Endoscopic retrograde cholangio-pancreatography (ERCP) and stenting was only successful in 28 patients and was associated with a significantly higher re-admission rate compared to patients in whom ERCP was not performed (60/179 vs. 4/27, p=0.050). The overall median (95% CI) survival was 145 (124-185) days. CONCLUSION: Current options for palliation of hilar cholangiocarcinoma provide good short term success but are all associated with significant early and late morbidity. Due to its low success and association with an increased re-admission rate, ERCP for definitive palliation should not be used in the first line staging and management of these patients.

Aged↗
PubMed2002

Novel growth factors involved in the pathogenesis of proliferative vitreoretinopathy.

AIMS: To determine whether hepatocyte growth factor (HGF) and connective tissue growth factor (CTGF) are expressed in human specimens of proliferative vitreoretinopathy (PVR) and to propose a model of PVR pathogenesis based upon the known activities of these growth factors. Methods Immunohistochemical methods (ABC Elite) were used to demonstrate the presence of HGF and CTGF in cryostat sections of five human PVR membranes. RESULTS: In each of the five PVR membranes, stromal cells were immunohistochemically positive for both HGF and CTGF. Based upon this information and the known actions of these growth factors, a model of PVR pathogenesis was developed. In this model, injury of the retina induces an inflammatory response that upregulates HGF expression inducing the formation of multilayered groups of migratory retinal pigment epithelial cells (RPE). These RPE, present in a provisional extracellular matrix, come in contact with vitreous containing TGF-beta. The TGF-beta is activated, upregulating expression of CTGF. Under the influence of TGF-beta and CTGF, RPE become myofibroblastic and fibrosis ensues. Retinal traction induces further detachment continuing the cycle of retinal injury. CONCLUSIONS: HGF and CTGF are expressed in PVR membranes and may play important roles in the pathogenesis of PVR. The expression and function of these growth factors should be critically examined in human PVR specimens, in in vitro cultures of RPE, and in animal models of PVR.

Connective Tissue Growth Factor↗
PubMed2001

Synthesis and biological evaluation of destruxin A and related analogs.

This report describes the development of an efficient solid-phase synthesis protocol and adaptation of reported solution phase procedures for the synthesis of the cyclic depsihexapeptide destruxin A and related analogs. The solid-phase method described is based on standard Fmoc peptide chemistry, including a new synthetic method for the assembly of the depsi bond-containing unit. In order to select analogs of destruxin A for synthesis and evaluation of insecticidal activity, the work of Hellberg et al., describing a set of Z-descriptors for amino acid side-chains comparing their physicochemical properties, was utilized. Destruxin A and 27 different analogs with structural variations in four residues were synthesized and insecticidal activity was evaluated via injections into tobacco budworm (Heliothis virescens) larvae. Several destruxin A analogs were found to be at least as potent as the native compound.

Animals↗
PubMed2000

Zinc nasal gel for the treatment of common cold symptoms: a double-blind, placebo-controlled trial.

Effective treatment for the common cold have been difficult to develop because so many different types of virus are responsible for this condition. Oral zinc has been studied as a possible means of preventing or alleviating symptoms, with mixed results. We studied a new approach to zinc therapy--an over-the-counter nasal gel formulation (Zicam)--to independently evaluate its efficacy as a treatment for the common cold. Our study was conducted at four sites over a 5-month period. The study group consisted of 213 patients with recent-onset(< or = 24) cold symptoms; 108 patients received zinc therapy, and 105 reviewed placebo. Symptom charts were used to track the duration and severity of each patient's symptoms. At study's end, the duration of symptoms was 2.3 days (+/-0.9)in the zinc group and 9.0 days (+/-2.5)in the control group--a statistically significant difference (p <0.05). These results provide evidence that zinc nasal gel is effective in shortening the duration of common cold symptoms off when taken within 24 hours of their onset.

Administration, Intranasal↗
PubMed1999

FGF-2 facilitates binding of SH3 domain of PLC-gamma1 to vinculin and SH2 domains to FGF receptor in corneal endothelial cells.

PURPOSE: To determine the cellular localization of the Src homology (SH)2 and SH3 domains of PLC-gamma1 and their cytoplasmic binding partners, living corneal endothelial cells were microinjected with the fusion proteins containing SH domains. METHODS: Fusion proteins were prepared from plasmid vectors, and the fusion proteins containing SH2-SH2 [(SH2)2], SH2-SH2-SH3 [(SH2)2-SH3] or SH3 were isolated using affinity chromatography. Following microinjection, immunolocalization was analyzed using confocal laser microscope. RESULTS: Microinjected SH domains were targeted to the subcellular location following stimulation with FGF-2: the SH3 domain appeared to be targeted to cytoskeleton; the (SH2)2 domain showed a dual localization in cytoplasm and plasma membrane; the (SH2)2-SH3 domain was predominantly localized at membrane and perinuclear sites. In the absence of stimulation by FGF-2, the microinjected fusion proteins remained at the injection sites. When cytoplasmic binding partners were determined by double-staining, the SH3 domain demonstrated colocalization with vinculin: the staining profile of the SH3 domain was identical to that of vinculin, which demonstrates characteristic punctated profiles. The punctated staining of SH3 disappears toward the basal membrane, while that of vinculin remains in all confocal optical sections. On the other hand, some fraction of the (SH2)2 domain was colocalized with FGF receptor at the membrane site. When PLC-gamma1 and F-actin were double-stained, the endogenous PLC-gamma1 demonstrated a diffuse cytoplasmic staining and/or perinuclear staining, while phalloidin staining demonstrated that all cells have filamentous cytoplasmic distribution of F-actin. CONCLUSIONS: These findings indicate that the SH3 domain directs PLC-gamma1 to bind to vinculin and that the SH2 domains may mediate the binding of PLC-gamma1 to receptor tyrosine kinase. Furthermore, they suggest that phosphorylation is not required for targeting of PLC-gamma1 to membrane or cytoskeleton sites.

Actins↗
PubMed1997

Vascular basement membrane pathology and Alzheimer's disease.

We have previously demonstrated that the capillary vascular basement membrane (VBM) is pathologically altered in Alzheimer's disease (AD). This microangiopathy is highlighted by the immunocytochemical localization of the three principal intrinsic VBM components: heparan sulfate proteoglycan, collagen type IV, and laminin. These three VBM components also immunolable amyloid deposits and senile plaque-associated glial processes. The present study examines the ultrastructure of the VBM in one brain region severely affected (temporal gyrus) and one relatively spared (cerebellum) from the lesions of AD in both AD and neurological control cases. The cross-sectional area as well as the width of the VBM were found to be greater in AD cortical capillaries. In addition, we found ultrastructural evidence for the activation of microglial-related perivascular cells, and their apparent extravasation through the VBM, findings consistent with the hypothesis that these cells are being recruited as part of a disease-related immune response. The recruitment of these "resting" microglial-like cells from their intra-VBM location to plaques and tangles in AD may explain (1) the thickening and vacuolization of the VBM; (2) the specificity of this VBM alteration to brain regions where there are plaques and tangles; and (3) the source of some of the large number of activated microglia in these affected areas. Thus, while VBM alterations may not be specific to AD, these changes appear to be specifically related to the disease process.

Aged↗
PubMed1996

Retinal nerve fiber layer thickness in normal human eyes.

PURPOSE: To measure the histologic thickness of the retinal nerve fiber layer (RNFL) in normal human eyes. METHODS: Human eyes were obtained at autopsy within 6 hours postmortem. The retina was dissected into four quadrants and serially sectioned in historesin. The RNFL thickness was measured histologically in all four quadrants at the disc margin and at regular intervals from the disc margin. Measurements of the RNFL thickness also were obtained at the fovea and in the retinal periphery. RESULTS: Ten eyes of ten white individuals were studied. Age (mean +/- standard deviation) was 53.1 +/- 19.6 years (range, 18-76 years). For the eyes studied, the disc area (mean +/- standard deviation) and cup:disc ratio (mean +/- standard deviation) were 1.92 +/- 0.1 mm2 and 0.3 +/- 0.08, respectively. Mean superior, inferior, nasal, and temporal RNFL thickness at the disc margin was 405, 376, 372, and 316 microns, respectively. In all four quadrants, the RNFL thickness decreased with increasing distance from the disc margin. The average superior and inferior RNFL thickness was inversely related to age (P = 0.033, P = 0.097, respectively). The average RNFL thickness was not related to disc area. The average RNFL thickness just superior, inferior, nasal, and temporal to the foveola was 27, 34, 26, and 12 microns, respectively. The average RNFL thickness just posterior to the ora serrata in the superior, inferior, nasal, and temporal retinal periphery was 8 to 11 microns. CONCLUSION: The peripapillary RNFL thickness in humans is thicker than that seen in nonhuman primates. The thinnest peripapillary RNFL is in the region of the papillomacular bundle. These data can be used to determine the accuracy of NFL analyzers in obtaining in vivo RNFL thickness measurements.

Adolescent↗
PubMed1995

Getting it all together. Systems should link their strategic and financial planning.

Foreseeing dramatic changes in healthcare delivery, the leaders of the Franciscan Health System (FHS) decided in the early 1990s to more closely link their strategic and financial planning. Though this cooperation was tentative at first, by 1993 both our planners and our chief financial officers shared certain assumptions about the future--above all, that the coming delivery model was managed care provided by integrated delivery systems (IDSs). Having agreed on our assumptions, we translated them into a vision statement, from which we derived four strategic goals: Advance the healing mission of our sponsors; Create a culture of continuous improvement in leadership, quality, innovation, cost-effectiveness, and measurable customer value; Create an environment that values and empowers those with whom we work; Develop, through partnering, an IDS that provides affordable care to our communities; Our goals established, we charted what we call a "crosswalk" between the strategic and financial aspects of our budgeting. We found that we had to think in a new way about capital. For example, we began investing as heavily in "soft" items like research, partnerships, and new services as in the traditional "bricks and mortar." This process is new for us, and developing it has not always been comfortable. But we believe it has helped us to more wisely allocate FHS's resources and thus give our system greater stability.

Budgets↗
PubMed1995

Characterization of ORG 20241, a combined phosphodiesterase IV/III cyclic nucleotide phosphodiesterase inhibitor for asthma.

The pharmacological profile of a novel cyclic nucleotide phosphodiesterase (PDE) inhibitor, Org 20241, has been characterized. The compound selectively inhibits PDE IV (pIC50, 5.2-6.1) and PDE III (pIC50, 4.4-4.6) from animal and human tissues. Org 20241 relaxed preparations of bovine trachea (pD2, 5.9 and 5.4), guinea pig trachea (pD2, 6.2 and 4.9) and human bronchi (pD2, 5.3 and 4.7) for histamine and methacholine-induced contractions, respectively. Rolipram and Org 20241 inhibited leukotriene B4-induced thromboxaneB2 (IC50, 0.3 and 1.4 microM, respectively) and H2O2 (IC50, 2.1 and 0.4 microM, respectively) production in guinea pig eosinophils. In phenylephrine (0.3 microM) precontracted rabbit aorta preparations, the PDE III inhibitor Org 9935 (pD2, 6.3 and 6.1 in the presence and absence of endothelium, respectively) was the most effective relaxant, whereas Org 20241 (pD2, 5.3 and 5.4 in the presence and absence of endothelium, respectively) was more effective than rolipram (pD2, 4.6 and 4.1 in the presence and absence of endothelium, respectively). Org 20241 relaxed rabbit aorta preparations and airway preparations at similar concentrations. In electrically stimulated rabbit cardiac papillary muscles, Org 20241 had little effect on contractility at concentrations up to 30 microM. Lower concentrations (10 microM) potentiated the inotropic effect of Org 9935. Whereas the PDE III inhibitor milrinone (1-100 microM) enhanced the rate of repolarization of guinea pig papillary muscles and shortened the effective refractory period, Org 20241 and rolipram (1-100 microM) did not reduce the action potential duration. In the presence of Org 20241 or rolipram, isoproterenol did not produce a greater increase in the rate of repolarization or reduction in the effective refractory period than in the absence of these PDE inhibitors. Org 20241 is a dual PDE IV/III inhibitor with some PDE IV selectively. This compound relaxes airways smooth muscle and inhibits eosinophil activation. The data indicate that such PDE IV/III inhibitors may be effective for the long-term therapy of asthma.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1991

Effects of Org 7797 on early, late and inducible arrhythmias following coronary artery occlusion in rats and dogs.

1. The class Ic steroidal antiarrhythmic agent, Org 7797, was compared with two other Ic agents, flecainide and propafenone for intravenous activity against ischaemia-related cardiac arrhythmias and for electrophysiological actions in vivo. In addition the haemodynamic effects of Org 7797 were assessed in greyhounds. 2. Org 7797 (0.5 mg kg-1) significantly reduced the expected incidence of early ischaemia-induced ventricular fibrillation (VF) in rats and greyhound dogs and at doses of 0.5-1.0 mg kg-1 antagonized reperfusion-induced arrhythmias. Comparative studies in rats showed Org 7797 to be 2-4 times more potent than flecainide or propafenone. 3. Org 7797 (0.5 mg kg-1) slowed intracardiac conduction in anaesthetized beagles and again was at least 2-4 times more potent than flecainide or propafenone. 4. Org 7797 (0.5 and 2.0 mg kg-1), flecainide (1.0 and 2.0 mg kg-1) or propafenone (0.5 and 2.0 mg kg-1), did not significantly prevent induction of tachyarrhythmias (VT) in dogs with 5-6 day old myocardial infarcts although all 3 drugs appeared to prevent induced VF. All 3 drugs (notably flecainide) did however reduce the VT rate. 5. All 3 drugs (1-2 mg kg-1) suppressed spontaneous tachyarrhythmias in conscious beagle dogs with 1-2 day old infarcts. Propafenone was the least effective. 6. In an antifibrillatory dose (0.5 mg kg-1), the major haemodynamic effect of Org 7797 was a 10% increase in peripheral vascular resistance. Stroke volume, cardiac output and coronary blood flow were unchanged. In therapeutic doses, Org 7797 was also less negatively chronotropic than flecainide.7. It was concluded that Org 7797 is a potent antifibrillatory agent which is haemodynamically well tolerated. Higher doses are required to suppress late ischaemia-induced tachyarrhythmias which suggest that its antifibrillatory effects are the consequence of an action other than, or in addition to, sodium channel block.

Animals↗
PubMed1991

Putting the poor first. A system's assessment project identifies community needs.

To enhance its mission of promoting compassionate and high-quality holistic healthcare to all people, especially the poor and underserved, Franciscan Health System (FHS), Aston, PA, launched the Service Area Needs Assessment (SANA) project in 1990. The project focused on population segments who live in the most economically deprived ZIP codes within member hospitals' service areas. SANA coordinators surveyed FHS hospitals about their programs and services for the poor and underserved and documented the programs' scope, value, and benefit to the community. When hospital personnel learned the results of the survey, they felt encouraged to interact with one another and learn more about their facilities' contributions to care for the poor and underserved in their communities. SANA coordinators and team members then interviewed community agency representatives, physicians, other service providers, and community residents. The agencies and healthcare providers identified several unmet needs that residents verified. However, the interviews revealed a gap between what providers think the problems of the poor are and what these individuals themselves believe their problems to be. As a result of these interviews, several hospitals have established programs to meet the identified needs. Of the 33 initiatives proposed, 16 represent new activities, 10 represent expansion of existing activities, and 7 represent collaboration with other organizations on new and existing programs. FHS believes the SANA project is just the beginning of a renewed commitment to caring for the poor and underserved.

Catchment Area, Health↗
PubMed1990

Morphologic association between microglia and senile plaque amyloid in Alzheimer's disease.

Alzheimer senile plaques are comprised of extracellular deposits of beta-amyloid. The cell type responsible for the secretion of this amyloid, however, is unknown. In the present study, compact amyloid 'stars' and the cellular elements directly apposed to them were examined at the ultrastructural level. In many cases, amyloid fibrils were closely interdigitated with the plasma membrane of cells with dark cytoplasm, dense bodies and distinctive nuclei. These cells were morphologically identified as microglia, the resident macrophages of the brain. Previous work has described an identical morphologic association between macrophages and several types of systemic and cerebral amyloidoses. Taken together, these data suggest that beta-amyloid may be secreted by microglia.

Aged↗
PubMed1990

Effects of amiodarone on cardiac electrophysiology and inducibility of arrhythmias in chronically infarcted dogs: late arrhythmias, haemodynamics, and sympatholytic actions.

The electrophysiological and antiarrhythmic effects of acute (2 and 10 mg/kg i.v.) and chronic (400 mg/day p.o. for 28 days) amiodarone (AM) treatment were compared in anaesthetised dogs with 5-6-day-old myocardial infarcts. Intravenous AM prolonged the RR interval, sinus node recovery time, the PR interval, and atrial to His conduction time by 36, 33, 25, and 36%, respectively. Corresponding increases after oral amiodarone were 50, 57, 12, and 26%. Atrial and His-Purkinje conduction times were unchanged. Atrial and ventricular refractory periods were increased especially after oral treatment. Oral AM additionally prolonged QRS, QT, and paced QT (by 4, 34, and 19%, respectively). Effects of oral AM on ventricular repolarisation and on the fast inward sodium current were confirmed in vitro. Both modes of AM administration protected against inducible arrhythmias, an effect that was more marked during normal sinus rhythm than during pacing in orally treated dogs. Oral amiodarone failed to protect against spontaneous late arrhythmias 24 h after infarction whilst both modes of administration noncompetitively inhibited isoprenaline-induced tachycardia. Oral AM reduced blood pressure (13%) and LV dP/dt/P (24%) whereas cardiac output was maintained by an increase in stroke volume. It was concluded that oral AM is haemodynamically well tolerated and that prolonged ventricular repolarisation enhanced by bradycardia together with sympatholytic actions may be important mechanisms for antiarrhythmic efficacy, whereas the mechanisms involved in i.v. efficacy are less clear but may depend, at least partly, on sympatholytic actions and perhaps (tentatively) on sodium channel block in Purkinje tissue.

Action Potentials↗
PubMed1990

Measurements of regional cerebral blood flow and cognitive performance in Alzheimer's disease.

Single photon emission computed tomography (SPECT) with 99mTc-HMPAO was used to image 26 patients with dementia of the Alzheimer type (DAT) and 10 healthy controls. Regional cerebral blood flow (rCBF) data indicated a relative sparing of the occipital regions in DAT. Normalisation to occipital flow illustrated highly significant CBF deficits in a number of cortical regions, particularly in the left and right posterior--temporal cortex in DAT compared to controls. The cognitive performance of DAT patients was measured using a clinical cognitive assessment procedure (CAMCOG) and numerous correlations between these scores and rCBF were obtained. The implications and value of this investigative technique are discussed.

Aged↗
PubMed1988

Evaluating researchers for the project.

This is the second in a series on a system-wide geriatric-care marketing initiative undertaken at Franciscan Health System, Chadds Ford, Pa. In the first article, the author outlined the process of gaining the voluntary involvement of internal market segments. In this article, the author details the process of putting out a request for proposal to market-research vendors.

Competitive Bidding↗