Biomedical subjects

Keith Robinson

Publications and source records attributed to Keith Robinson.

9 recordsLinked to original sources

PubMed2006

Toxic vessel reaction to an absorbable polymer-based paclitaxel-eluting stent in pig coronary arteries.

OBJECTIVES: The goal of this study was to evaluate a new drug-eluting stent (DES) comprising a bioabsorbable polymer eluting a moderate dose of paclitaxel in a clinically relevant animal model. BACKGROUND: Although DES limit restenosis, adverse vascular pathologies and toxicities continue to be of major concern. Optimization of DES components, especially completely absorbable polymers, may reduce these toxicities. METHODS: Bare-metal (BM), absorbable polymer coating only (POLY), and polymer-based paclitaxel-eluting (PACL) stents were implanted in porcine coronary arteries using intravascular ultrasound (IVUS) to optimize stent apposition. The dose density of paclitaxel was 0.30-0.35 mcg/mm2, with in vitro elution studies demonstrating a gradual elution over 6-8 weeks. The animals were terminated at 1 week, 1 month and 3 months. Histopathologic and histomorphometric analyses were perform. RESULTS: The arteries with PACL showed extensive smooth muscle cell necrosis at 1 week and poor apposition of stent struts at 1 month (malapposition measured as gap width between strut and internal elastic lamina), with greater gap width compared to the BM and POLY groups (0.22 mm +/- 0.02 vs. 0.03 mm +/- 0.02 and 0.02 mm +/- 0.01, respectively; p < 0.001). At 3 months, the PACL group showed rebound neointimal thickness and histological percent stenosis compared to the BM group (0.48 mm +/- 0.14 vs. 0.07 mm +/- 0.02, respectively; p < 0.001 and 59% +/- 11 vs. 17% +/- 2, respectively; p < 0.001). CONCLUSIONS: Despite in vitro data showing slow, sustained release of paclitaxel from a bioabsorbable polymer, the porcine coronary artery model demonstrated a sequence of medial necrosis, stent malapposition and late neointimal thickening. Since the therapeutic window for paclitaxel may be narrower than currently inferred, thorough preclinical testing coupled with the polymer development process for stents eluting paclitaxel is needed.

Absorbable Implants↗

PubMed2005

Falling risk factors in Parkinson's disease.

OBJECTIVE: To identify falling risk factors that are potentially modifiable among individuals who have idiopathic Parkinson's disease. DESIGN: A between group comparison of 19 fallers and 21 nonfallers who have Parkinson's disease, across an array of variables that have been identified as falling risk factors among the elderly and among those who have Parkinson's disease. RESULTS: Several variables were demonstrated significantly to distinguish fallers: disease duration and severity; dyskinesias associated with the use of dopaminergic agents; freezing; postural instability; depression; fear of falling; impaired fine motor control and motor planning in the feet; decreased proximal strength and muscular endurance in the legs; and a higher level of disability. CONCLUSIONS: Several of these variables can be viewed a potentially modifiable during a future intervention trial that aims to reduce falls in those who have Parkinson's disease using multidimensional risk factor modification.

Accidental Falls↗

PubMed2003

Fatal cholestatic liver failure associated with gemcitabine therapy.

Drug-induced hepatotoxicity accounts for more than a third of the cases of acute liver failure in the United States. In complex medical conditions, the diagnosis of drug-induced liver injury may be confounding and, specifically, the potential hepatotoxicity of chemotherapeutic agents may be easily overlooked. Two fatal cases of cholestatic hepatotoxicity have been previously reported, clearly implicating gemcitabine therapy. We report a third fatal case of cholestatic liver failure that we think is strongly linked to the use of gemcitabine. This chemotherapeutic agent is a fluorine analog with broad-spectrum antitumor activity commonly used in the treatment of breast, lung, prostate, and cervical cancer. The case we report is of a 45-year-old woman with a history of metastatic breast cancer to her spine. The patient was in remission for two years before she presented with a compensated mixed hepatitis of mild to moderate severity. Inpatient work-up found metastases to the right humerus and inferior pubic ramus, but none in the liver. Gemcitabine and carboplatin therapy was initiated for relapse of breast cancer. The patient's liver enzyme elevation diminished, but did not normalize before the start of chemotherapy. She received four courses of gemcitabine/carboplatin and subsequently presented with decompensated, severe cholestatic hepatitis. Transjugular liver biopsy displayed marked cholestasis and hepatocellular injury consistent with drug-induced hepatoxicity. Gemcitabine has been extensively studied in the oncology literature and at this time is thought to be a low-risk hepatotoxin causing hepatic adaptation and transient, reversible liver enzyme elevation, rarely leading to termination of gemcitabine therapy for solid tumors. We believe that gemcitabine therapy, particularly in the setting of preexisting liver injury or metastases to the liver, increases the relative risk of severe and potentially fatal hepatic injury possibly by idiosyncratic and dose-dependent mechanisms. We recommend careful monitoring and dose adjustment of gemcitabine in patients with abnormal liver function tests or evidence of hepatic metastases until further study clarifies this issue.

Adenocarcinoma↗

PubMed2002

Osteogenic sarcoma presenting with lung metastasis.

A patient with osteogenic sarcoma presenting with lung metastases is discussed with attention to appropriate diagnosis, staging, and treatment. Multimodality treatment options using chemotherapy, orthopedic surgery and thoracic surgery are presented. Physical medicine and rehabilitation evaluation and treatment are included. Current research options are discussed.

Adult↗

PubMed2002

Aerobic exercise intervention improves aerobic capacity and movement initiation in Parkinson's disease patients.

Parkinson's Disease (PD) is a progressive neurologic disorder, which includes an inability to activate appropriate muscle activity. Very little research has analyzed aerobic exercise for PD patients. The purpose of this study was to investigate the effect of a 16 week aerobic exercise intervention on aerobic capacity and movement initiation (MI) time for PD patients. With 8 PD subjects (Hoehn & Yahr stage 2), 4 completed the exercise intervention. Peak VO_2scores significantly improved (26%) Choice MI improved from 532 ms to 415 ms, while simple MI improved from 285 ms to 261 ms. The improvement in aerobic capacity suggests that PD patients may benefit from exercise just as much as a normal population. The change in MI indicates that aerobic exercise may reduce the detrimental effects of neuromuscular slowing within PD patients, by improving the subjects' ability to initiate and perform appropriate movement patterns.

Aged↗

PubMedDate not supplied

Prevention of intimal hyperplasia; Initial results with low-dose beta-radiation applied by an external vascular polymer wrap.

OBJECTIVE: Endovascular brachytherapy, delivered by a variety of catheter-based devices, has proven clinically effective for the inhibition of neointimal hyperplasia (NIH) after coronary and peripheral balloon/stent angioplasty. No platform, however, has been developed to deliver low-dose radiation in concert with vascular surgical operations. The purpose of this study was to evaluate the vascular response following balloon injury to the rabbit carotid artery, with and without topical low-dose 45Ca, applied by an external vascular "wrap". METHODS: Twelve rabbit carotid arteries were subjected to balloon injury by embolectomy catheter. The common carotid artery was then "wrapped" circumferentially with a biostable polyurethane membrane (Nanoskin Secant Medical, Perkasie, PA), without radiation (n = 6), or with radiation (n = 6) (45Ca approximately 50 microCi). The animals were sacrificed at 4 weeks for histologic assessment of the treated vessels. RESULTS: The 45Ca wrap inhibited NIH evidenced by trends towards reduction of intimal area (0.46 +/- 0.19 control carotid vs. 0.35 +/- 0.15 (45)Ca-treated carotid arteries; P = .11), maximal intimal thickness (0.21 +/- 0.08 vs. 0.16 +/- 0.05; P = .12), average intimal thickness (0.12 +/- 0.06 vs. 0.08 +/- 0.03; P = .08), marginally significant reduction in percent area stenosis (33 +/- 15% vs. 21 +/- 9%; P = .06) and marked neointima suppression in areas immediately adjacent to 45Ca wrap remnants. Medial necrosis (P = .003), however, was observed slightly more for 45Ca-treated carotid arteries versus control arteries. CONCLUSION: Low-dose 45Ca beta-radiation labeled onto a polyurethane membrane appears to inhibit NIH in an animal model.

Angioplasty, Balloon↗

PubMedDate not supplied

Safety of intramyocardial injection of autologous bone marrow cells to treat myocardial ischemia in pigs.

OBJECTIVE: The purpose of this study is to determine the potential adverse consequences of intracardiac injections of bone marrow mononuclear cells (BMCs) to facilitate the revascularization of ischemic myocardium. BACKGROUND: Bone marrow mononuclear cells are used to treat heart failure, though there are few studies that evaluated the safety of BMC transplantation for chronic myocardial ischemia. METHODS: The pigs received coronary ameroid constrictors to induce chronic myocardial ischemia and left ventricular dysfunction. At 4 weeks, autologous BMCs were injected intramyocardially by Boston Scientific Stiletto catheter with low-dose (10(7) cells) or high-dose BMC (10(8)). Control animals received saline. Blood samples were collected for hematological and chemical indices, including cardiac enzyme levels at regular time intervals postinfarction. At 7 weeks, animals underwent electrophysiological study to evaluate the arrhythmic potential of transplanted BMC, followed by necropsy and histopathology. RESULTS: No mortalities were associated with intramyocardial delivery of BMC or saline. At Day 0, the total creatine phosphokinase (CPK) was in the normal range in all groups. All groups had significant elevations in CPK after ameroid placement, with no significant differences between groups. At 7 weeks, CPK in all groups had returned to pretreatment levels. Electrophysiological assessment revealed that one control animal had an inducible arrhythmia. No arrhythmias were induced in low- or high-dose BMC-treated pigs. There were no histopathological changes associated with BMC injection. CONCLUSION: This study showed, in a clinically relevant large-animal model, that catheter-based intramyocardial injection of autologous BMC into ischemic myocardium is safe.

Animals↗

PubMedDate not supplied

Topical application of beta-radiation to reduce intimal hyperplasia after carotid artery balloon injury in rabbit. A possible application for brachytherapy in vascular surgery.

PURPOSE: Endovascular brachytherapy for the prevention of intimal hyperplasia (IH) and restenosis after balloon/stent angioplasty has proven effective both in animal preparations and clinical trials. A variety of beta-emitting isotopes and catheter-based devices have been developed for the delivery of low-dose radiation in clinical coronary and peripheral trials. No platform, however, has yet been developed for brachytherapy in concert with vascular surgical operations. The purpose of this study was to evaluate the vascular histopathologic response following balloon injury to rabbit carotid arteries with and without topically applied low-dose beta-radiation. METHODS: The beta-emitting isotope strontium-90 (Sr-90) was conjugated onto the matrix of polypropylene (PLYP) mesh. Rabbit carotid arteries were balloon-injured with a #2 embolectomy catheter. Six carotid arteries were wrapped with nonradioactive PLYP mesh (controls) and Sr-90 ( approximately 90 microCi) PLYP mesh in order to deliver low-dose radiation to the vessel wall from the external (adventitial) surface. Tissue was harvested at 6 weeks and processed for histologic examination. RESULTS: There was consistent blockade of fibrocellular neointima formation with virtually no neointima present in all treated segments, compared to moderate neointima formation in controls. Medial thinning and smooth muscle cell (SMC) necrosis were also associated with topical brachytherapy. CONCLUSION: beta-Radiation applied by an externally wrapped PLYP mesh labeled with Sr-90 markedly suppressed neointima formation in an animal vascular surgical injury model. Further studies, however, are necessary to determine a suitable isotope and dosage for clinical application.

Administration, Topical↗

PubMedDate not supplied

External heating of stents by radio waves: pilot studies in rabbit aorta.

PURPOSE: This experiment was designed to assess the feasibility of radio frequency energy delivered by a prototype radio frequency generator inductive heating device (REVAX) positioned external to the body, for transient heating of stents after arterial implant. METHODS AND MATERIALS: Twenty-one New Zealand White rabbits underwent stenting of their infrarenal aorta. Nine rabbits were stented and immediately placed in the REVAX for external stent heating with internal temperature probes in place. Twelve rabbits were stented and 3 days later either heated or placed in the generator as a sham for 20 min. The animals were terminated 28 days later. RESULTS: The REVAX was able to heat the aortic stents in a controlled fashion; in Phase II experiments, the stent temperature was raised to 42 degrees C for 20 min. In Phase I mild necrosis was noted at the stent struts. In Phase II, necrosis and mineralization of the media was seen at the stent struts, and evidence of neointimal suppression was observed. CONCLUSION: This study demonstrated that external heating of stents in a blood vessel in a live animal via radio frequency energy is feasible. Further studies will be needed to assess whether any specific heating regimen might inhibit fibrocellular neointimal hyperplasia.

Animals↗