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Biomedical subjects

Jeffrey Schwartz

Publications and source records attributed to Jeffrey Schwartz.

At least 19 recordsLinked to original sources

High-yield activation of scaffold polymer surfaces to attach cell adhesion molecules.

Zirconium tetra(tert-butoxide) reacts with surface amide groups of polyamide nylon 6/6 to give (eta(2)-amidate)zirconium complexes in high yield. These surface complexes react to bond the cell-adhesive peptide arginine-glycine-aspartic acid (RGD) to the polymer surface. A surface loading of 0.18 nmol/cm(2) of RGD is achieved, which is 20-1000 times higher than previously reported attainable on natural or synthetic polymers by other strategies. Approximately 40% of the nylon surface is covered by the RGD, which gives a surface that is both stable to hydrolysis and highly active for cell adhesion and spreading in vitro.

Animals↗

Subpopulations of corticotrophs in the sheep pituitary during late gestation: effects of development and placental restriction.

The prepartum surge in fetal plasma cortisol is essential for the normal timing of parturition in sheep and may result from an increase in the ratio of ACTH to proopiomelanocortin (POMC) in the fetal circulation. In fetuses subjected to experimental induction of placental restriction, the prepartum surge in fetal cortisol is exaggerated, whereas pituitary POMC mRNA levels are decreased, and in vitro, unstimulated ACTH secretion is elevated in corticotrophs nonresponsive to CRH. We therefore investigated the changes in the relative proportions of cells expressing POMC, ACTH, and the CRH type 1 receptor (CRHR(1)) shortly before birth and during chronic placental insufficiency. Placental restriction (PR) was induced by removal of the majority of placental attachment sites in five ewes before mating. Pituitaries were collected from control and PR fetal sheep at 140 d (control, n = 4; PR, n = 4) and 144 d (control, n = 6; PR, n = 4). Pituitary sections were labeled with specific antisera raised against POMC, ACTH, and CRHR(1). Three major subpopulations of corticotrophs were identified that expressed POMC + ACTH + CRHR(1), ACTH + CRHR(1), or POMC only. The proportion of pituitary corticotrophs expressing POMC + ACTH + CRHR(1) decreased (P < 0.05) between 140 (control, 60 +/- 1%; PR, 66 +/- 4%) and 144 (control, 45 +/- 2%; PR, 56 +/- 6%) d. A significantly higher (P < 0.05) proportion of corticotrophs expressed POMC + ACTH + CRHR(1) in the pituitary of the PR group compared with controls. This study is the first to demonstrate subpopulations of corticotrophs in the fetal sheep pituitary that differentially express POMC, ACTH, and CRHR(1) and the separate effects of gestational age and placental restriction on these subpopulations of corticotrophs.

Adrenocorticotropic Hormone↗

Characterization of self-assembled organic films using differential charging in X-ray photoelectron spectroscopy.

Differential charging is often regarded as a problem in X-ray photoelectron spectroscopic studies, especially for insulating or partially conducting samples. Application of a positive bias can reduce the effect of differential charging by attracting stray electrons from the system, thereby compensating for the electron loss. On the other hand, differential charging effect can be enhanced by the application of a negative bias to the sample during spectrum acquisition. The successful use of the differential charging technique to distinguish between multi- and monolayer organophosphonate films on oxide-covered silicon has been reported. A detailed description of this technique is now presented which shows how differential charging can be used as an important tool for the characterization of self-assembled films deposited on various surfaces. The dependence of this technique on the conductivity of the substrate has been investigated by studying the spectral behavior of the deposited films of phosphonic acid on conducting, semiconducting, and insulating samples (stainless steel, silicon, and glass). Application of either positive or negative dc electrical bias affects the carbon core-level (C1s) line shape and intensity, which is dependent on the atom's physical location above the surface.

Electric Conductivity↗

Advanced surface modification of indium tin oxide for improved charge injection in organic devices.

A new method is described for surface modification of ITO with an electroactive organic monolayer. This procedure was done to enhance hole injection in an electronic device and involves sequential formation of a monolayer of a pi-conjugated organic semiconductor on the indium tin oxide (ITO) surface followed by doping with a strong electron acceptor. The semiconductor monolayer is covalently bound to the ITO, which ensures strong adhesion and interface stability; reduction of the hole injection barrier in these devices is accomplished by formation of a charge-transfer complex by doping within the monolayer. This gives rise to very high current densities in simple single layer devices and double layer light emitting devices compared to those with untreated ITO anodes.

Journal Article↗

Measuring the surface roughness of sputtered coatings by microgravimetry.

A novel application of quartz crystal microgravimetry is described to enable determination of the roughness of native and sputtered oxide coatings. The technique is applicable to coatings that may be too rough for accurate atomic force microscopic imaging where measurements may be limited by the dimensions of the probe tip.

Journal Article↗

Direct measurement of surface complex loading and surface dipole and their effect on simple device behavior.

Tin complexes of phenoxide ligands having a range of dipole moments were prepared on the surface of indium-tin oxide (ITO). Surface complex loadings and stoichiometries were measured by quartz crystal microgravimetry. Work functions of ITO substrates treated with these various surface complexes were measured using a Kelvin probe. Surface complex dipole moments were then calculated based on measured surface loadings. Changes in the ITO work function effected by surface phenoxide complex introduction correlate with these surface complex dipole moments and with total surface dipole per unit area, and current densities in simple hole-only diode devices also correlate with these total surface dipoles.

Journal Article↗

Comparative properties of siloxane vs phosphonate monolayers on a key titanium alloy.

A direct comparison of surface loading, interface shear strength, and interface hydrolytic stability was made between a phosphonate and two siloxane monolayers formed on the native oxide surface of Ti-6Al-4V. Surface loading for the phosphonate was ca. four times greater (on a nanomole/area basis) than for the siloxanes; mechanical strengths per surface-bound molecule were comparable, but the hydrolytic stability (pH 7.5) of the siloxanes was poor. These results suggest that phosphonate monolayer interfaces are more desirable than comparable siloxane ones for applications where such interfaces contact even slightly alkaline water.

Journal Article↗

Self-assembled monolayers of alpha,omega-diphosphonic acids on Ti enable complete or spatially controlled surface derivatization.

Alpha,omega-diphosphonic acids self-assemble on the native oxide surfaces of Ti or Ti-6Al-4V. Heating gives strongly bonded phosphonate monolayers. Infrared and X-ray spectroscopic and water contact angle data show that the films are bonded to the surface by one phosphonate unit; the other remains a phosphonic acid. Surface loadings were measured by quartz crystal microbalance procedures. Mechanical shear strengths for the films were also measured; these do not correlate simply with surface loadings. Films formed from 1,12-diphosphonododecane were treated with zirconium tetra(tert-butoxide) to give surface Zr complex species; derivatives of these surface complexes are stable to hydrolysis under physiological conditions and are mechanically strong. The complexation reaction can be accomplished over the entire surface; alternatively, dropwise application of the alkoxide to the surface enables spatial control of deposition. The cell attractive peptide derivative RGDC can be bound to these surface Zr alkoxide complexes through (maleimido)-alkylcarboxylate intermediates. Surfaces modified with RGDC were shown to be effective for osteoblast binding and proliferation.

Cell Adhesion↗

Easy and efficient bonding of biomolecules to an oxide surface of silicon.

A new method is described to attach biological molecules to the surface of silicon. Semiconductors such as Si modified with surface-bound capture molecules have enormous potential for use in biosensors for which an ideal detection platform should be inexpensive, recognize targets rapidly with high sensitivity and specificity, and possess superior stability. In this process, a self-assembled film of an organophosphonic acid is bonded to the native or synthesized oxide-coated Si surface as a film of the correspondingphosphonate. The phosphonate film is functionalized to enable covalently coupling biological molecules, ranging in size from small peptides to large multi-subunit proteins, to the Si surface. Surface modification and biomolecule coupling procedures are easily accomplished: all reactions can proceed in air, and most take place under ambient conditions. The biomolecule-modified surfaces are stable under physiological conditions, are selective for adhesion of specific cells types, and are reusable.

Animals↗

Need for hospice and palliative care services in patients with end-stage heart failure treated with intermittent infusion of inotropes.

BACKGROUND: Hospice and palliative care programs to relieve suffering and optimize management of terminally ill patients have grown rapidly in the United States. However, there are no data on the need for these services among patients with end-stage heart failure receiving intermittent infusion of intravenous inotropes. HYPOTHESIS: The need for hospice and palliative care programs among patients in end-stage heart failure who receive intermittent infusion of inotropes is investigated. METHODS: The study included all stable patients with refractory heart failure symptoms treated with inotropes in our outpatient unit. A total of 73 patients (65 +/- 12 years; left ventricular ejection fraction 22 +/- 9%; New York Heart Association class 3.6 +/- 0.4) were seen during a 49-month period. Of these, 35 patients (48%) met hospice or palliative care evaluation criteria upon referral but were offered, and accepted, the alternative of parenteral inotropes. In all, 1,737 individual outpatient treatment sessions were given, with a mean of 24 +/- 19 sessions per patient (range 5 to 118 sessions), representing a minimum of 9,948 h of inotrope therapy. RESULTS: A total of 18 (25%) patients died, 6 (8%) patients were withdrawn from the program (3 by their primary physicians and 3 because of significant travel limitations); 4 (5%) patients required continuous intravenous home therapy; and 44 (61%) patients were discharged with significant improvement in their heart failure symptoms. Only 7 of the 18 patients who died had received hospice or palliative care intervention, mainly for the sake of comfort and to ease the transition among family members. The rest of the patients were comfortable and had accepted the natural evolution of their disease; they were not interested in or did not require hospice or palliative care intervention. Of the patients discharged from the outpatient cardiac infusion unit, the interval free of heart failure symptoms after the final infusion treatment ranged from 201 to 489 days, with no need for hospitalization or emergency room visits. CONCLUSION: Our results demonstrate that intermittent infusion of intravenous inotropes can be safely administered and can improve symptoms in a significant number of patients, probably by slowing the natural progression of heart failure. Although the full clinical impact of inotrope therapy in an outpatient setting has not been fully defined, other nonhemodynamic-related benefits should be sought and investigated. Our results suggest that intermittent infusion of intravenous inotropes is one of the prominent variables that requires particular attention. In our experience, the institution of intermittent infusions of intravenous inotropes can, in fact, modify end-stage heart failure symptoms that, in most patients, are currently perceived to lead to a terminal event. Thus, appropriate use of intermittent infusion of intravenous inotropes may not only improve functional class and symptoms in a significant number of patients identified as terminal by their poor response to conventional therapy, but it may also facilitate better utilization of hospice and palliative care resources among patients with end-stage heart failure. Furthermore, the need for hospice and palliative care in patients with heart failure should be revisited in view of adjuvant treatment options such as intermittent infusion of intravenous inotropes.

Aged↗

Bonding self-assembled, compact organophosphonate monolayers to the native oxide surface of silicon.

A new method is described to prepare strongly bonded, compact monolayer films of alkyl- or arylphosphonates on the native oxide surface of Si (SiO(2)/Si). This method is illustrated for octadecyl- and alpha-quarterthiophene-2-phosphonates. For both cases, AFM shows comprehensive coverage of the SiO(2)/Si surface. The thickness of the continuous film of 4TP/SiO(2)/Si was measured both by AFM and by X-ray reflectivity to be ca. 18 A. Direct gravimetric analysis shows surface coverage by alpha-quarterthiophene-2-phosphonate to be about 0.66 nmol/cm(2), which corresponds to molecular packing in the film close to that of crystalline alpha-quarterthiophene. Coverage by octadecylphosphonate was ca. 0.90 nmol/cm(2), corresponding to a cross-sectional area of about 18.5 A(2)/molecule, consistent with close-packed alkyl chains.

Journal Article↗

Chemistry between magnesium and multiple molecules in tris(8-hydroxyquinoline) aluminum films.

Metal organic contacts are at the basis of devices such as organic light emitting diodes (OLEDs). Here, we report a theoretical investigation of the chemical interaction between a Mg atom and an organic film made of tris(8-hydroxyquinoline)aluminum (Alq3) molecules. The latter is modeled either by an isolated molecule or by a bulk crystal. Using first-principles molecular dynamics for structural optimization, we find that an isolated Alq3 molecule and a Mg atom form an ion-pair. However, when the metal atom interacts with molecules in a bulk crystalline environment, we find that an organometallic complex is energetically preferred over the ion-pair. The complex formation is an effect of the environment which makes possible the interaction of the metal atom with several adjacent molecules. Here, our calculated O(1s) and N(1s) core level shifts agree well with recent experimental data on Alq3 films exposed to Mg. Our results resolve the apparent contradiction between experiment and predictions made in previous calculations in which a single Alq3 molecule was used to model a thin film.

Journal Article↗

Ontogeny of corticotropin-releasing hormone binding in anterior pituitaries of fetal sheep.

OBJECTIVES: Previous studies have shown that anterior pituitary expression of corticotropin-releasing hormone type 1 receptor (CRH-R1) decreases during late gestation. This study sought to determine whether this reduction is from a decrease in the number of cells expressing CRH receptors or a decrease in the number of CRH receptors per cell. METHODS: Fetuses were studied at 100 days' gestational age (100 dGA), 120 dGA, or 140 dGA. Dispersed anterior pituitary cells were incubated with or without fluorescein-conjugated CRH (FL-CRH). FL-CRH binding was assessed by flow cytometry. RESULTS: The number of CRH receptors per cell decreased at 120 dGA and 140 dGA. However, because of an increase in the percentage of cells expressing CRH receptors at 120 dGA, the total receptor index was similar at 100 dGA and 120 dGA. The receptor index tended to decrease at 140 dGA. CONCLUSION: FL-CRH binding was decreased at 140 dGA due to a decrease in the percentage of cells binding CRH and the number of CRH receptors per cell. This could contribute to the decrease in CRH-stimulated adrenocorticotropin release during late gestation in fetal sheep.

Animals↗

Finding meaning in medical necessity.

Managed care organizations have become partners in patient care through their representatives/liaisons---care managers. This article uses personal experiences and relevant literature to highlight the professional conflicts care managers face in the struggle to fulfill two main clinical functions: applying criteria to determine medical necessity and educating practitioners and patients about effective and efficient treatments. Many care managers struggle to maintain cordial relationships with colleagues, while determining which requests for treatment are necessary versus discretionary, and insuring treatment excellence.

Case Management↗

An unusual case of recurrent Loffler endomyocarditis of the aortic valve.

Idiopathic hypereosinophilic syndrome is a rare systemic disease with an unexplained elevated eosinophil count. Loffler endomyocarditis is hypereosinophilic syndrome with endocardial fibrosis and restrictive cardiomyopathy. The atrioventricular valves are frequently involved, causing valvular regurgitation. Previously, there has been one case report of combined aortic and mitral valve involvement with Loffler endomyocarditis that was treated with bivalvular replacement. We describe a previously healthy 50-year-old man diagnosed with Loffler endomyocarditis complicated by peripheral thromboembolism and severe aortic regurgitation due to valve fibrosis and fibrotic vegetation on the aortic valve. He underwent embolectomy and aortic valve replacement in addition to treatment for his hypereosinophilia. He later presented with cardiomyopathy with severe aortic insufficiency due to the destruction of the aortic valve prosthesis by sterile fibrinous vegetation. To our knowledge, this is the second case in the literature in which Loffler endomyocarditis involves the aortic valve and the first patient in whom only the aortic valve is involved.

Aortic Valve↗

Controlling the work function of indium tin oxide: differentiating dipolar from local surface effects.

Indium tin oxide (ITO) reacts with tetra(tert-butoxy)tin to give surface bound alkoxytin species. Ligand exchange occurs in these surface bound species by reaction with substituted phenols. The speciation of surface phenoxides was measured in ultrahigh vacuum by X-ray photoelectron spectroscopy, as was the work function for the surface modified ITO. It is shown that the molecular dipole moment of the phenol correlates strongly with the measured ITO work function change; no such correlation exists between the acidity of the phenol and this measured change in work function. Results are consistent therefore with an electrostatic model and not with one involving electronegativities of the ligated phenoxide oxygens.

Journal Article↗