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Biomedical subjects

Marc D Feldman

Publications and source records attributed to Marc D Feldman.

18 recordsLinked to original sources

Coronary stents: a materials perspective.

The objective of this review is to describe the suitability of different biomaterials as coronary stents. This review focuses on the following topics: (1) different materials used for stents, (2) surface characteristics that influence stent-biology interactions, (3) the use of polymers in stents, and (4) drug-eluting stents, especially those that are commercially available.

Alloys↗

Impact of physiological variables and genetic background on myocardial frequency-resistivity relations in the intact beating murine heart.

Conductance measurements for generation of an instantaneous left ventricular (LV) volume signal in the mouse are limited, because the volume signal is a combination of blood and LV muscle, and only the blood signal is desired. We have developed a conductance system that operates at two simultaneous frequencies to identify and remove the myocardial contribution to the instantaneous volume signal. This system is based on the observation that myocardial resistivity varies with frequency, whereas blood resistivity does not. For calculation of LV blood volume with the dual-frequency conductance system in mice, in vivo murine myocardial resistivity was measured and combined with an analytic approach. The goals of the present study were to identify and minimize the sources of error in the measurement of myocardial resistivity to enhance the accuracy of the dual-frequency conductance system. We extended these findings to a gene-altered mouse model to determine the impact of measured myocardial resistivity on the calculation of LV pressure-volume relations. We examined the impact of temperature, timing of the measurement during the cardiac cycle, breeding strain, anisotropy, and intrameasurement and interanimal variability on the measurement of intact murine myocardial resistivity. Applying this knowledge to diabetic and nondiabetic 11- and 20- to 24-wk-old mice, we demonstrated differences in myocardial resistivity at low frequencies, enhancement of LV systolic function at 11 wk and LV dilation at 20-24 wk, and histological and electron-microscopic studies demonstrating greater glycogen deposition in the diabetic mice. This study demonstrated the accurate technique of measuring myocardial resistivity and its impact on the determination of LV pressure-volume relations in gene-altered mice.

Animals↗

Surface modification of functional self-assembled monolayers on 316L stainless steel via lipase catalysis.

Lipase catalyzed esterification of therapeutic drugs to functional self-assembled monolayers (SAMs) on 316L stainless steel (SS) after assembly has been demonstrated. SAMs of 16-mercaptohexadecanoic acid (-COOH SAM) and 11-mercapto-1-undecanol (-OH SAM) were formed on 316L SS, and lipase catalysis was used to attach therapeutic drugs, perphenazine and ibuprofen, respectively, on these SAMs. The reaction was carried out in toluene at 60 degrees C for 5 h using Novozyme-435 as the biocatalyst. The FTIR spectra after surface modification of -OH SAMs showed the presence of the C=O stretching bands at 1745 cm(-1), which was absent in the FTIR spectra of -OH SAMs. Similarly, the FTIR spectra after the reaction of the -COOH SAM with perphenazine showed two peaks in the carbonyl region, a peak at 1764 cm(-1), which is the representative peak for the C=O stretching for esters. The second peak at 1681 cm(-1) is assigned to the C=O stretching of the remaining unreacted terminal COOH. XPS spectra after lipase catalysis with ibuprofen showed a photoelectron peak evolving at 288.5 eV which arises from the carbon (C=O) of the carboxylic acid of the drug (ibuprofen). Similarly for -COOH SAMs, after esterifiation we see a small, photoelectron peak evolving at 286.5 eV which corresponds to the C in the methylene groups adjacent to the oxygen (C-O), which should evolve only after the esterification of perphenazine with the -COOH SAM. Thus, lipase catalysis provides an alternate synthetic methodology for surface modification of functional SAMs after assembly.

Catalysis↗

Detection of vulnerable plaque in a murine model of atherosclerosis with optical coherence tomography.

OBJECTIVES: The aim of this study was to evaluate the feasibility of optical coherence tomography (OCT) to identify the components of vulnerable plaques in a well-established murine model of human atherosclerosis. BACKGROUND: Although the pathologic features that predict plaque rupture at autopsy are well known, the development of a technology to identify these high risk features in vivo is lacking. OCT uses reflected light to provide histology-like images of plaque with higher resolution than competing imaging modalities. Whether OCT can reliably identify the features of an atherosclerotic plaque that define it as vulnerable-thin fibrous cap, large lipid core, and high percent of lipid in the artery-requires further study. METHODS: OCT images of the atherosclerotic innominate artery segments from the apolipoprotein E knockout (apoE(-/-)) mice were recorded and correlated with histology in both in vivo (n = 7) and well as in ex vivo experiments (n = 12). RESULTS: Excellent correlation between the OCT and histology measurements for fibrous cap thickness, lipid core size, and percentage lipid content was found. The fibrous cap thicknesses examined span those of human fibrous caps known to rupture (< 65 microm). Regions of greatest light reflection in OCT images were observed when calcium hydroxy-apatite was scattered in lipid, less in fibrous tissue, and least in lipid. CONCLUSIONS: These findings suggest that OCT holds promise for the identification of features defining vulnerable plaque including fibrous cap thickness, lipid core size, and the percentage of lipid content.

Animals↗

Hypersensitivity cases associated with drug-eluting coronary stents: a review of available cases from the Research on Adverse Drug Events and Reports (RADAR) project.

OBJECTIVES: We undertook the review of all available cases of hypersensitivity reactions after placement of a drug-eluting stent (DES) and classified potential causes. BACKGROUND: Six months after the approval of the first DES, the Food and Drug Administration (FDA) reported 50 hypersensitivity reactions after stent placement but later concluded these were due to concomitantly prescribed medications such as clopidogrel. Nevertheless, the FDA continued to receive reports of hypersensitivity. METHODS: Reports available from April 2003 through December 2004 for hypersensitivity-like reactions associated with the sirolimus-eluting stent (CYPHER, Cordis Corp., Miami Lakes, Florida) and paclitaxel-eluting stent (TAXUS, Boston Scientific Corp., Natick, Massachusetts) were reviewed. Sources of reports included the FDA's adverse-device-event database, the published literature, and investigators from the Research on Adverse Drug/Device events And Reports (RADAR) project. Causality was assessed using standardized World Health Organization criteria. RESULTS: Of 5,783 reports identified for the DES in the FDA database, 262 unique events included hypersensitivity symptoms. Of these reports, 2 were certainly and 39 unlikely caused by clopidogrel and 1 was certainly, 9 probably, and 13 unlikely caused by the DES. From all sources, we identified 17 distinct cases that were probably or certainly caused by the stent, of which 9 had symptoms that lasted longer than four weeks. Four autopsies confirmed intrastent eosinophilic inflammation, thrombosis, and lack of intimal healing. CONCLUSIONS: The FDA reports and autopsy findings suggest that DES may be a cause of systemic and intrastent hypersensitivity reactions that, in some cases, have been associated with late thrombosis and death.

Coronary Vessels↗

Mathematical modeling of the course and prognosis of factitious disorders: a game-theoretic approach.

A mathematical model using simple concepts of repeated games is proposed to model the course and prognosis of factitious disorders. Although simple, the model seems capable of explaining the yet unknown mechanisms underlying the variable course of factitious disorders. One of the notable results of this study is the significant effect of involved physicians in the treatment process on the course of the disease. Particularly, the doctor's error rate in realizing whether the symptoms are real or factitious can considerably affect the course of the disease. This is the first paper to apply a mathematical model to factitious disorders.

Factitious Disorders↗

The Research on Adverse Drug Events and Reports (RADAR) project.

CONTEXT: In 1998, a multidisciplinary team of investigators initiated RADAR (Research on Adverse Drug events And Reports), a clinically based postmarketing surveillance program that systematically investigates and disseminates information describing serious and previously unrecognized adverse drug and device reactions (ADRs). OBJECTIVE: To describe the structure, operations, and preliminary findings from the RADAR project and related dissemination efforts by pharmaceutical suppliers and the US Food and Drug Administration (FDA). DESIGN: After identifying a serious and unexpected clinical event suitable for further investigation, RADAR collaborators postulated clinical hypotheses and derived case series and incidence estimates from physician queries, published and unpublished clinical trials, published case reports, FDA databases, and manufacturer sales figures. RESULTS: RADAR investigators identified 16 types of serious ADRs among 1699 patients, of whom 169 (10%) died as a result of the reaction. Initial cases were identified by 7 RADAR investigators, 4 collaborating physicians, 2 attorneys, and by reviewing 3 published reports. Additional sources included queries of occupational health programs and medical directors of interventional cardiology laboratories (3 types of ADRs), published manuscripts and clinical trials (11 types of ADRs), review of medical records at a RADAR site (2 types of ADRs), unpublished clinical trial reports (3 types of ADRs), and reports from attorneys, family members, or patients (4 types of ADRs). Incidence estimates, ranging from 0.4% to 33%, were derived from 5 clinical trial reports, 2 physician queries, and 2 observational databases. Laboratory support for hypotheses included identification of 3 neutralizing antibodies and 3 histopathological findings. ADR reports were disseminated as 8 revised package inserts, 7 "dear doctor" letters, and 9 peer-reviewed articles. CONCLUSION: A new, clinically based, hypothesis-driven approach to postmarketing surveillance may supplement existing regulatory surveillance systems and improve patient safety.

Adverse Drug Reaction Reporting Systems↗

Nonlinear conductance-volume relationship for murine conductance catheter measurement system.

The conductance catheter system is a tool to determine instantaneous left ventricular volume in vivo by converting measured conductance to volume. The currently adopted conductance-to-volume conversion equation was proposed by Baan, and the accuracy of this equation is limited by the assumption of a linear conductance-volume relationship. The electric field generated by a conductance catheter is nonuniform, which results in a nonlinear relationship between conductance and volume. This paper investigates this nonlinear relationship and proposes a new nonlinear conductance-to-volume conversion equation. The proposed nonlinear equation uses a single empirically determined calibration coefficient, derived from independently measured stroke volume. In vitro experiments and numerical model simulations were performed to verify and validate the proposed equation.

Animals↗

Celiac disease as a manifestation of Munchausen by proxy.

In typical cases of Munchausen by proxy maltreatment, a mother feigns or produces illness in her child. Her primary goal is to accrue emotional gratification, and no mental disorder better accounts for the behavior. We present the first published case in which the principal manufactured ailment was celiac sprue. In addition, a panoply of other ailments ranging from seizures to behavioral abnormalities was reported. The case is also very unusual in the involvement of the paternal grandmother and, to a lesser extent, the paternal grandfather as the perpetrators. Although definitive intervention to protect the child occurred only after 7 years had passed, multidisciplinary teamwork ultimately resulted in a successful outcome for the child, who is now doing well.

Celiac Disease↗

Enhanced left ventricular systolic function early in type 2 diabetic mice: clinical implications.

It is unclear whether the increase in availability of substrates for energy production in diabetes can lead to enhanced systolic function early in the disease, before the onset of structural changes to the myocardium. To examine this issue, BKS.Cg-m +/+ Lepr db (db/db) mice with type 2 diabetes and wild type controls had left ventricular pressure-volume relationships determined in situ. We demonstrated that the db/db mice, when compared to their wild type controls, generated greater left ventricular pressure and an enhancement of left ventricular systolic function based on enhanced power/EDV, positive dP/dt, preload recruitable stroke work, dP/dt--EDV relationship, and curvilinear end-systolic elastance. This enhancement in systolic function occurred despite the db/db mice having greater body weight, but similar preload (end-diastolic volume) and afterload (effective arterial elastance). We postulate that the previously described enhancement in renal glomerular filtration rate seen early in type 2 diabetes may be in part due to enhanced left ventricular systolic function early in this disease.

Animals↗

Design of instrumentation and data-acquisition system for complex admittance measurement.

Instantaneous left ventricular volume measurements have been made for many years using a tetrapolar conductance catheter. The main objective is to determine the efficiency of the beating heart, using a tetrapolar catheter inserted in the left ventricle of transgenic mice. The effect of the parallel myocardium contribution must be removed from the total measurement. A dual-frequency technique involving 1 kHz and 100 kHz was chosen because it has been established that the imaginary part (the capacitive reactance) of the complex admittance of the cardiac muscle is much smaller in the lower frequency than at the higher frequency. The design involves generation of an accurate frequency source for both the frequencies careful selection of operational amplifiers for the current conversion stage so that the current is not too large to kill the mouse and that it is capable of performing at high frequencies. The band pass filter stage involved careful design with minimal overlap of the pass bands of both the channels. The overall circuit was designed so that there is minimal shift in the phase due to the circuit elements alone. Work also involved design of GPIB--based data acquisition system using LabVIEW and a digital oscilloscope for effective data acquisition even at high frequencies, which are normally limited by the sampling frequency. This data acquisition system is currently being used in laboratory studies in vivo.

Animals↗

Enhancement of contractility with sustained afterload in the intact murine heart: blunting of length-dependent activation.

BACKGROUND: It has been hypothesized that because of its rapid heart rate, the intact murine heart functions near maximal contractility in the basal state. If this hypothesis is correct, then the fast and slow components of myocardial length-dependent activation should be blunted compared with larger mammals. METHODS AND RESULTS: Mice (n=24) were anesthetized, and via an open chest, LV pressure-volume relationships were determined by a dual-frequency conductance catheter system. Baseline pressure-volume relationships were determined during transient occlusion of the inferior vena cava, and repeat measurements were made after 1 (n=10) and 7 (n=21) minutes of sustained aortic occlusion. Control experiments were performed in a subset of mice (n=3). For baseline to 1 minute, an increase in afterload (maximal pressure 95+/-9 to 126+/-7 mm Hg; P<0.001) and effective arterial elastance (5.9+/-3.1 to 9.2+/-3.9 mm Hg/microl; P<0.001) resulted in an increase in end-diastolic volume (31+/-8 to 35+/-9 microL; P<0.001). The result was maintenance of stroke volume (17+/-6 to 15+/-6; P=NS) owing to an increase in contractility (leftward shift in V100 [the volume of end-systolic elastance at 100 mm Hg], 24+/-9 to 16+/-5 microL; P<0.001). No additional augmentation of systolic function was found at 7 minutes. CONCLUSIONS: This study demonstrates that the fast phase of length-dependent activation is intact but not the slow phase, consistent with murine myocardium functioning near maximal contractility in the basal state.

Animals↗

Use of a blood substitute to determine instantaneous murine right ventricular thickening with optical coherence tomography.

BACKGROUND: A satisfactory imaging technique to determine regional wall thickening of the murine myocardium is not available. Although cardiovascular imaging with light offers a novel solution, application is problematic because scattering by erythrocytes causes significant optical attenuation. METHODS AND RESULTS: Optical coherence tomography (OCT) is a technique for detailed resolution imaging of highly scattering biological tissues. To reduce the high level of blood scattering, a method was devised whereby murine blood was replaced with a hemoglobin-based blood substitute. The scattering and absorption properties of in vitro preparations of whole blood and dilutions of blood with a blood substitute were determined with a spectrophotometer and an inverse-adding doubling algorithm. OCT imaging of the same dilutions demonstrated a significant reduction in scattering at a hematocrit <5%. A fiber-optic OCT imaging system was used to image the murine right midventricular free wall before and after isovolumic replacement with blood substitute. Strong light attenuation prevented full thickness imaging before replacement, whereas visualization of the full ventricular thickness was possible after replacement. Baseline and imaging hematocrits were 52.4+/-3.8% and 3.7+/-1.2%, respectively. End-systolic and end-diastolic thickness values were 0.458+/-0.051 mm and 0.352+/-0.047 mm. Percent thickening fraction was 30.8+/- 7.5%. CONCLUSION: Optical imaging of the intact beating murine right ventricle was substantially improved by isovolumic blood replacement with a hemoglobin-based blood substitute. Although the current study has been directed toward imaging the murine heart, a blood substitute may be applied to various optical diagnostic and therapeutic techniques under investigation in cardiovascular medicine.

Animals↗

Munchausen by Proxy in an international context.

OBJECTIVE: The professional literature on Munchausen by Proxy (MBP) abuse consists of more than 400 articles, chapters, and books. Most have come from a handful of English-speaking industrialized countries. Our aims were to establish the extent to which published work about MBP has emerged from outside these countries, and to determine the characteristics of any reported cases. METHOD: Numerous health care computer databases were queried, and the results supplemented by materials accumulated less formally. RESULTS: We identified 59 articles from 24 countries describing at least 122 cases in 9 different languages. Among cases in which the information was available, the mother was the sole perpetrator in 86%, the victim was aged between 3 years and 13 years in 52%, and the victim was male in 54%. The presentations of MBP appear to be similar across the world with the exception of induced apnea, which emerged as notably uncommon in this review. An extensive table presents the characteristics of each case. CONCLUSIONS: MBP clearly is not a phenomenon unique to Western or highly medicalized societies. This form of abuse is being increasingly recognized and reported throughout the world. The literature from the US, Canada, UK, Australia, and New Zealand often presupposes access to resources, such as subspecialists and social service agencies, that may be seriously constrained in other countries. The contributions of professionals elsewhere will be vital in ensuring that the efforts in English-speaking industrialized settings to develop standards of care encompass an international perspective.

Child↗