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J Finkelstein

Publications and source records attributed to J Finkelstein.

88 records · Page 5Linked to original sources

Multicenter epidemiologic and health services research on therapeutics in the HMO Research Network Center for Education and Research on Therapeutics.

Research and education programs in therapeutics that combine the data, organizational capabilities, and expertise of several managed care organizations working in concert can serve an important role when a single organization is not large enough to address a question of interest, when diversity in populations or delivery systems is required, and when it is necessary to establish consistency of results in different settings. Nine members of the HMO Research Network, a consortium of health maintenance organizations (HMOs) that perform public domain research, have formed a Center for Education and Research on Therapeutics (CERT), sponsored by the Agency for Healthcare Research and Quality, to conduct multicenter research in therapeutics. The CERT uses a distributed organizational model with shared leadership, in which data reside at the originating organization until they are needed to support a specific study. Extraction of data from the host computer systems, and some manipulation of data, is typically accomplished through computer programs that are developed centrally, then modified for use at each site. For complex studies, pooled analysis files are created by a coordinating center, and then analysed by investigators throughout the HMOs. It is also possible to contact HMO members when necessary. This multicenter environment has several benefits, addressing: (1) a wide array of questions about the safety and effectiveness of therapeutics, (2) the impact of efforts to change clinicians' and patients' behavior, and (3) pharmacoeconomic and pharmacogenetic questions.

Community Networks↗

In vitro, release of cholecystokinin from hypothalamus and frontal cortex of Sprague-Dawley, Zucker lean (Fa/-) and obese (fa/fa) rats.

Cholecystokinin (CCK) has been suggested as a putative satiety factor, whose site of action is in the hypothalamus. The genetically obese (fa/fa) Zucker rat has been proposed as a model of human obesity. Though hypothalamic tissue levels of CCK did not vary between the fa/fa rat and age-matched lean littermates (25.5 +/- 5.7 vs. 27.6 +/- 5.2 pmoles/g tissue) we sought to determine if the releasability of hypothalamic and cortical CCK was the same in lean and obese rats. The in vitro superfusion paradigm was used to study the release of CCK and substance P (sP) from hypothalamus, and CCK and vasoactive intestinal polypeptide (VIP) from frontal cortex. The potassium stimulated release of CCK from obese rat hypothalamic tissue was significantly higher than from lean rat hypothalamus (3.62 +/- 0.3 vs. 1.91 +/- 0.3 fmole equivalents CCK-8/mg tissue/10 min). Similarly, sP release was exaggerated in obese rats in a parallel fashion (5.56 +/- 0.44 vs. 2.761 +/- 0.46 fmoles/mg tissue/10 min). However, the potassium stimulated release of CCK and VIP from cortical tissue was the same in all three groups of rats. The obese Zucker rat thus, may have an anomalous release of CCK and sP from the hypothalamus, but not from the frontal cortex, an area not presumably associated with satiety.

Animals↗

Lung inflammation induced by endotoxin is enhanced in rats depleted of alveolar macrophages with aerosolized clodronate.

Clodronate liposomes were given to rats via intratracheal inhalation to investigate the importance of alveolar macrophages (AMs) in inhaled endotoxin-induced lung injury. When AM depletion was maximal (87% to 90%), rats were exposed to lipopolysaccharide (LPS) or saline. Neither clodronate nor saline liposomes induced an influx of neutrophils (PMNs) into the lungs. However, depleted LPS-exposed rats had 5- to 8-fold higher numbers of lavage PMNs and greater lavage cell reactive oxygen species release compared to undepleted rats. Although AM depletion by itself did not significantly increase inflammatory cytokine expression in lung tissue, LPS-induced message levels for interleukin (IL)-1alpha, IL-1beta, IL-6, and tumor necrosis factor (TNF)-alpha were approximately 2-fold higher in AM-depleted rats compared to undepleted rats. These results indicate that cells other than AMs can recruit inflammatory cells into the lungs during acute LPS-induced injury and that AMs play an important suppressive role in the innate pulmonary inflammatory response.

Administration, Inhalation↗

In vivo imaging and evaluation of platelet accumulation vs. time at arterial injury site.

The feasibility of quantitatively imaging platelet deposition over time following angioplasty of the abdominal aorta in a rabbit model, with and without antiplatelet treatment, was investigated. Ten male 3-4 kg rabbits were balloon de-endothelialized and placed on 2% cholesterol diet for eight weeks. Group A was untreated. In Group B, donors and recipients were treated with aspirin (5 mgm/kg) prior to and after angioplasty. Platelets were labelled with indium-111. Labelled platelets were injected just prior to PTA and images of 100,000 counts were obtained immediately and at 30 minutes, 1 hour, and 24 hours. In Group A, increased activity of angioplasty site vs. nonangioplastied aorta was seen immediately. This focal increase became more marked in hypercholesterolemic animals over the 24-hour period. In Group B, both hypercholesterolemic and normocholesterolemic, no focal uptake could be documented on sequential scans. This method and model are promising for in vivo evaluation of platelet-vessel wall interactions, in the setting of angioplasty and antiplatelet therapy.

Angioplasty, Balloon↗

Photodynamic therapy for the treatment of metastatic lesions in bone: studies in rat and porcine models.

This study represents the first reported use of photodynamic therapy (PDT) for metastatic bone lesions and specifically, as a treatment for spinal metastases. A model of bone metastasis in rat confirmed the efficacy of benzoporphyrin derivative-monoacid-mediated PDT for treating lesions within the spine and appendicular bone. Fluorimetry confirmed the selective accumulation of drug into the tumor(s) at 3 h post-injection. 48 h post-light delivery into the vertebral body of the rat spine loss of bioluminescent signal and histological analyses of sectioned spine confirmed MT-1 tumor cell kill in vivo as previously confirmed in vitro using an established cell viability assay. Porcine vertebrae provided a model comparable to that of human for light propagation and PDT response. Histological examination of vertebrae 48 h post-PDT revealed a necrotic radius of 0.6 cm with an average fluence rate of 4.3 mW/cm2. Non-necrotic tissue damage was evident up to 2 cm out from the treatment fiber. Results support the application of PDT to the treatment of primary or metastatic lesions within bone.

Animals↗

A nasal trumpet orthosis to maintain nares openings and respiratory function for patients with facial burns: a case report.

Management of facial burns is a challenge to the burn team because it may lead to functional and cosmetic compromise. Severe scarring of the nares may lead to nasal occlusion. This article introduces a method of maintaining nasal patency that allows respiratory exchange through the use of a custom-fabricated, semirigid tubular orthosis. The technique for fabrication is reviewed, and the use of the device is addressed through a case report. This inexpensive, readily available device is useful in preventing nasal occlusion that results from scar formation.

Adult↗