Galactose-α-1,3-galactose (alpha-gal) allergy: first pediatric case in a series of patients in Spain.

INTRODUCTION AND OBJECTIVES: Allergy to galactose-α-1,3-galactose (alpha-gal) is a peculiar form of food allergy generally manifesting as an anaphylactic reaction hours after mammalian meat consumption, due to the presence of specific IgE against this oligosaccharide. In addition, immediate anaphylaxis may develop after exposure to other sources of alpha-gal, such as monoclonal antibody cetuximab, vaccines, plasma expanders or anti-snake venoms. Sensitization to alpha-gal has also been implicated in the rapid degeneration of biological valve implants, and recognized as a cause of occupational disease in cattle raisers. The implication of tick bites in this type of sensitization has been accepted by all the research groups dedicated to this disease. PATIENTS AND METHOD: The present study describes the clinical and sensitization characteristics of 39 patients diagnosed with alpha-gal allergy in the hospitals of our province (Lugo, Monforte de Lemos and Burela, Spain). RESULTS: Most patients were middle-age males. Of note, is the fact that the series includes the first pediatric patient reported in Spain to date. The predominant clinical manifestations were urticaria or delayed anaphylaxis after consumption of mammalian meat. Seventy-four percent of the patients reported having suffered a previous tick bite, and the clinical presentation of anaphylaxis was significantly more prevalent in those with a persistent local reaction following the bite than in those with no such reaction (p = 0.032). CONCLUSIONS: A review is also made of the disorder which, due to its variable clinical expression, is referred to as alpha-gal syndrome. The study concludes that a diagnosis of alpha-gal allergy should be considered in patients with urticaria-anaphylaxis of uncertain origin or manifesting after the administration of vaccines or products of bovine/porcine origin.

Anafilaxia perioperatoria / Perioperative anaphylaxis

La anafilaxia perioperatoria es un cuadro clínico que puede amenazar la vida del paciente, producido por fármacos o sustancias usados durante la anestesia. Después de una anafilaxia debe realizarse un estudio alergológico para identificar el agente responsable y prevenir recurrencias. La incidencia global se estima de 1 entre 10.000-20.000 anestesias. Los agentes más frecuentemente implicados son los bloqueantes neuromusculares, látex y antibióticos. El diagnóstico inicial es clínico y en el tratamiento es esencial la adrenalina. En este artículo se describe la clínica, pruebas diagnósticas, así como protocolos de prevención y tratamiento del cuadro de anafilaxia perioperatoria. Será importante desarrollar protocolos de detección y manejo precoz de estas reacciones en circuitos de cirugía ambulatoria y establecer un adecuado seguimiento posterior (AU)

Perioperative anaphylaxis may be a life threatening clinical condition and is typically due to the results of drugs used for anesthesia. Once anaphylaxis occurs, allergy studies are essential to identify the responsible agent so to prevent recurrences. The overall incidence is estimated at 1 in 10,000-20,000 anesthetic procedures. The most commonly involved agents are neuromuscular blocking agents, latex and antibiotics. The initial diagnosis is presumptive; including clinical signs and adrenalin is the treatment of choice. The aim of this article is to review etiology, diagnosis, prevention and treatment of perioperative anaphylaxis. It will be important to produce action protocols to ensure the detection of these reactions of anaphylaxis in outpatient surgery and to establish the correct follow-up (AU)

Structural and electrical characterization of ultra-thin SrTiO3 tunnel barriers grown over YBa2Cu3O7 electrodes for the development of high Tc Josephson junctions.

The transport properties of ultra-thin SrTiO(3) (STO) layers grown over YBa(2)Cu(3)O(7) electrodes were studied by conductive atomic force microscopy at the nano-scale. A very good control of the barrier thickness was achieved during the deposition process. A phenomenological approach was used to obtain critical parameters regarding the structural and electrical properties of the system. The STO layers present an energy barrier of 0.9 eV and an attenuation length of 0.23 nm, indicating very good insulating properties for the development of high-quality Josephson junctions.

Detection of Chlamydia trachomatis in pregnant women by the Papanicolaou technique, enzyme immunoassay and polymerase chain reaction.

OBJECTIVE: To compare Papanicolaou staining, enzyme immunoassay (EIA) and the polymerase chain reaction (PCR) techniques for detecting Chlamydia trachomatis in pregnant women. STUDY DESIGN: Endocervical specimens were taken randomly from 125 pregnant women with or without symptoms. These women attended their first medical consultation at the Regional General Ignacio Zaragoza Hospital. Samples were analyzed for detection of C trachomatis. When results differed between tests, specimens were evaluated by direct immunofluorescence staining. RESULTS: The prevalence of chlamydial infection was 2.4%. The characteristics of patients positive for Chlamydia were: average age, 24 years; first sexual encounter at age 21 years, one partner and six to nine months of gestation. The sensitivity, specificity, accuracy, positive predictive values and negative predictive values were 100%, 99.18%, 99.20%, 75% and 100%, respectively, for Papanicolaou staining; 100%, 92.62%, 92%, 25% and 100% for EIA; and 100%, 100%, 100% and 100% for PCR. CONCLUSION: Both Papanicolaou staining and PCR were adequate for diagnosis of C trachomatis infection. EIA was not reliable and therefore is not recommended for use as a diagnostic technique in a pregnant population with low risk and low prevalence.

In vitro study of biosynthesis of protoporphyrin IX induced by delta-aminolevulinic acid in normal and cancerous cells of the human cervix.

BACKGROUND: delta-Aminolevulinic acid (ALA) is recognized as the starter in the biosynthesis of the heme group, the structural basis of cytochromes, chlorophylls, biliary pigments, and other porphyrins. It is the first intermediary in the biosynthesis of protoporphyrin IX (PpIX), and of the heme group. PpIX is present in low concentration in normal cells, and in high concentration in tumor cells. METHODS: The accumulation of protoporphyrin IX (PpIX) induced by delta-aminolevulinic acid (ALA) was tested in two cervico-uterine cancer cell lines (HeLa and CaLo), and in normal human cervical epithelial (NHCE) cells. RESULTS: The optimal concentration of ALA that induced maximum levels of intra- and extracellular accumulation of PpIX in both HeLa and NHCE cells was 300 micrograms of ALA/mL, and for CaLo cells, 150 micrograms/mL. The viability of HeLa, CaLo, and NHCE cells exposed to ALA measured 81, 98, and 84%, respectively. The optimal time for accumulation of PpIX, both intra- and extracellular, was 4 h for HeLa and NHCE cells and 5 h for CaLo cells per 24 h of exposure to optimal concentrations of ALA. After the maximum level of PpIX accumulation was reached, there was a gradual decrease until there was only a small quantity. A statistically significant difference (p < 0.0001) was found in the accumulation of PpIX, depending on the concentrations of ALA used as well as between cervical cancer cell lines and NHCE cells (p < 0.0001). The concentration ratio of PpIX for NHCE and HeLa cells was 1:7, and for NHCE and CaLo cells, 1:5. CONCLUSIONS: These results are important for determining the usefulness of the sensitizer (PpIX).

Influence of local delivery of the protein tyrosine kinase receptor inhibitor tyrphostin-47 on smooth-muscle cell proliferation in a rat carotid balloon-injury model.

Smooth-muscle cell proliferation in response to arterial injury represents an important etiologic factor in restenosis after angioplasty. Tyrphostin-47, a protein tyrosine kinase inhibitor, inhibits smooth-muscle cell proliferation in vitro. In this study tyrphostin-47 was incorporated into matrixes to determine whether prolonged local delivery would result in a reduction of neointimal proliferation after arterial injury in a rat carotid balloon-injury model. A polymer matrix (polylactic polyglycolic acid copolymer and pluronic gel F-127, mean matrix weight 7.83 +/- 0.39 mg) was loaded with tyrphostin-47 (25% w/w). Release studies demonstrated delivery of 11% of the incorporated drug over a 21-day release period. In cell culture, tyrphostin-47 released from the polymer matrix produced a reduction in smooth-muscle cell proliferation (p < 0.0007). Balloon denudation injury of the left common carotid artery of 34 animals was performed. In 12 animals, polymer matrixes containing tyrphostin-47 were wrapped around the injured arteries to provide prolonged drug delivery (estimated dosage 28 micrograms/kg/24 hr); in 10 animals a polymer matrix without tyrphostin-47 was implanted; and in 12 animals only balloon injury was performed. The mean neointimal cross-sectional areas, luminal areas, and intima/media ratios were not significantly different among animals receiving local treatment with tyrphostin-47, sham polymer after injury, or balloon injury without polymer implantation. We conclude that despite inhibition of smooth-muscle cell proliferation by tyrphostin-47 in vitro, sustained local delivery of this tyrosine kinase inhibitor does not result in a reduction of neointimal proliferation in the rat carotid injury model.

Local intraluminal infusion of biodegradable polymeric nanoparticles. A novel approach for prolonged drug delivery after balloon angioplasty.

BACKGROUND: Several perfusion balloon catheters are under investigation for local drug delivery; however, sustained tissue drug levels are difficult to achieve with these techniques. To overcome this problem, sustained-release, biodegradable nanoparticles represent a potential alternative for prolonged local delivery. METHODS AND RESULTS: A biodegradable polylactic-polyglycolic acid (PLGA) copolymer was used to formulate nanoparticles. Fluorescent-labeled nanoparticles were intraluminally administered in a single, 180-second infusion after balloon injury in the rat carotid model. Localization and retention at different time points and biocompatibility of nanoparticles were evaluated. To evaluate the potential of the system in the prevention of neointimal formation, dexamethasone was incorporated into the particles and delivered locally as above. Nanoparticles were seen in the three layers of the artery at 3 hours and 24 hours. At 3 days, they were mainly present in the adventitial layer, decreasing at 7 days, with no fluorescent activity at 14 days. The PLGA nanoparticles appeared to be fully biocompatible. In the dexamethasone nanoparticle study, a significant amount of dexamethasone was present in the treated segment for up to 14 days after a single infusion, with no plasma levels detected after the first 3 hours. There was a 31% reduction in intima-media ratio in animals treated with local dexamethasone nanoparticles compared with control. CONCLUSIONS: Nanoparticles successfully penetrated into the vessel wall and persisted for up to 14 days after a short, single intraluminal infusion. Local administration of nanoparticles with incorporated dexamethasone significantly decreased neointimal formation. This methodology appears to have important potential for clinical applications in local drug delivery.

Umbilical cord beta-endorphin and early childhood motor development.

Stress during delivery has been associated with elevated umbilical cord plasma beta-endorphin levels. Published research suggests that much cord beta-endorphin originates from fetal pituitary. Intact pituitary function is required for normal growth and development. Relationships between cord beta-endorphin and child development have not been previously reported. We measured paired maternal and cord plasma beta-endorphin concentration in a set of 106 low risk deliveries by solid phase two-site immunoradiometric assay. Geometric mean maternal and cord beta-endorphin concentrations were 128 pg/ml and 196 pg/ml, respectively, with corresponding ranges of 33-533 pg/ml and 70-579 pg/ml. Cord beta-endorphin concentration was significantly higher than maternal, regardless of delivery mode, and the two were significantly correlated (r = 0.231; P = 0.017). Multiple regression modeling showed that forceps delivery, maternal beta-endorphin concentration, bradycardia, vaginal delivery, and birth weight each made independent contributions to elevated cord beta-endorphin. Depressed cord beta-endorphin predicted more day 2 neurological soft signs, lower 6-month mental development, and lower 36-month motor score on psychometric tests of the children. Poorer fine motor control and coordination were predominantly associated with lower beta-endorphin. Level of cord beta-endorphin independent of delivery stress exerted the primary influence upon child motor development. Higher levels of stress-independent beta-endorphin may play a direct role in motor development.

[Regulation of uterine cellular proliferation with estrogens and growth factors]. / Regulación de la proliferación celular uterina por estrógenos y factores de crecimiento.

In this paper the role of estrogen and growth factors in the uterine cellular proliferation is analyzed. The evidences indicate that the estradiol-stimulate cell division is associated with the induction of expression of a variety of growth factors from the all major uterine cell types (epithelia, stroma and myometrium). These growth factors amplify the estrogen proliferation signal in autocrine and/or paracrin fashion. The best-studied growth factors in the uterine response to estradiol are epidermal growth factor (EGF) and insulin-like growth factor (IGF-1). Uterine cell proliferation is a complex process that involves interactions of several growth factors, ovarian steroids hormones action and cell to cell signaling.

[Use of an index of social welfare for health planning at a municipal level]. / Uso de un índice de bienestar social para la planificación de la salud a nivel municipal.

OBJECTIVE: This paper analyzes the relationship between a living standards index for small areas based on census data and information on morbidity and health care utilization. MATERIAL AND METHODS: The information was gathered through a health interview survey of a random sample of 1 238 households from rural areas of Tlaxcala, Mexico. RESULTS: The population from localities with lower living standards showed significantly higher prevalences of morbidity and worse self-reported health status measures, as compared to localities with higher living standards. On the contrary, higher living standards were related with a greater utilization of health services. CONCLUSIONS: The approach proved to be useful in discriminating localities and areas of high and low prevalence of morbidity and utilization of health care services, which in turn could be used to identify those areas where needs are greatest. The implications of the results for health planning and resource allocation (based on population health needs and underlying social conditions) at the local level are discussed.

Role of intimal hyperplasia and arterial remodeling after balloon angioplasty: an experimental study in the atherosclerotic rabbit model.

The arterial response to injury appears to be an important factor in the development or restenosis. Traditionally, intimal hyperplasia has been thought to be the primary mechanism responsible for restenosis. However, recent studies have found that arterial remodeling is a major determinant of lumen loss after balloon angioplasty. In this study, we evaluated the actual separate contributions of intimal hyperplasia and arterial remodeling to the restenotic process after balloon angioplasty in the atherosclerotic rabbit model. One month after induction of focal atherosclerotic lesions, femoral arteries were randomized to receive treatment with either two or six balloon inflations. One group of rabbits was euthanized immediately after angioplasty to evaluate the initial degree of injury with each dilation strategy ("acute group"), and the rest were euthanized 28 days after angioplasty ("chronic group"). Arteries that had been treated with six inflations had a higher injury score than those treated with two (4.0+/-3.0 versus 1.9+/-1.5, P<.05). In the chronic group, there was a significant increase in intimal area in the six inflation-treated arteries compared with the two-inflation group (0.617+/-0.06 versus 0.432+/-0.05 mm2, P<.004). However, there was no significant difference in lumen cross-sectional area between groups. By multivariate analysis, the most important independent predictor of lumen area was the external elastic lamina (EEL) area, although the degree of intimal thickening was also a significant independent predictor. There was a strong, positive correlation between intimal area and EEL area: the larger the intimal area, the larger the EEL area (r=.703, P<.0001). The intimal area was similar in both restenotic and nonrestenotic lesions. In contrast, EEL area was significantly larger (due to remodeling) in nonrestenotic lesions. This study confirms previous findings that the degree of injury determines the degree of neointimal proliferation and supports recent findings that chronic arterial remodeling plays a major role in the final lumen area. Understanding and controlling the remodeling process rather than concentrating solely on intimal hyperplasia may yield better results after balloon angioplasty in the future.

Influence of blockade at specific levels of the coagulation cascade on restenosis in a rabbit atherosclerotic femoral artery injury model.

BACKGROUND: The relation among the coagulation cascade, its individual proteins, and the response to vascular injury is largely undefined. We have evaluated the effect of four probes that block specific levels of coagulation cascade on neointimal hyperplasia in the atherosclerotic rabbit arterial injury model. METHODS AND RESULTS: Focal femoral atherosclerosis was induced by air-desiccation injury and hypercholesterolemic diet in 48 New Zealand White rabbits, followed by balloon angioplasty. Active-site inactivated factor VIIa (DEGR-VIIa), which blocks the binding of factor VIIa to tissue factor, was administered (n = 12 arteries) by intravenous bolus (1 mg/kg) at the time of balloon angioplasty and followed by infusion of 50 micrograms.kg-1.h-1 for 3 days; for the control (n = 13 arteries), 150 U heparin was injected as bolus and followed by infusion of saline at 50 microL.kg-1.min-1. Recombinant tissue factor pathway inhibitor (TFPI), which binds factor Xa and inhibits the tissue factor-factor VIIa complex and factor Xa, was given as a 1 mg/kg bolus followed by 15 micrograms.kg-1.min-1 infusion for 3 days (n = 17 arteries). Recombinant tick anticoagulant peptide (TAP; n = 15 arteries) and hirudin (n = 14 arteries), which block factor Xa and thrombin, respectively, were administered as a 1 mg/kg bolus followed by 5 micrograms.kg-1.min-1 infusion for 3 days. These three groups had their own controls (n = 14 arteries). There were no differences among treatment groups in preangioplasty and postangioplasty minimal luminal diameter (MLD) by angiography. The mean MLD 21 days after balloon angioplasty was significantly different between control and DEGR-VIIa-treated groups (0.74 +/- 0.25 and 1.24 +/- 0.27 mm, respectively; P = .0001) and between the TFPI-treated group and others (0.88 +/- 0.21 mm for control, 0.97 +/- 0.22 mm for hirudin-treated, 0.98 +/- 0.14 mm for TAP-treated, and 1.32 +/- 0.21 mm for TFPI-treated arteries; P = .0001 by ANOVA). By quantitative histological analysis, the ratio of neointimal cross-sectional area compared with the area of internal elastic lamina in the DEGR-VIIa-treated group was significantly less than control (0.48 +/- 0.12 versus 0.67 +/- 0.12, P = .0001), and the ratio of neointimal cross-sectional area to the area demarcated by the internal elastic lamina of the TFPI-treated group was significantly reduced compared with the other groups (0.46 +/- 0.20 for TFPI-treated, 0.67 +/- 0.15 for hirudin-treated, 0.61 +/- 0.15 for TAP-treated, and 0.64 +/- 0.13 for control groups; P = .003). CONCLUSIONS: Treatment with DEGR-VIIa or TFPI for 3 days in this rabbit atherosclerotic injury model reduced angiographic restenosis and decreased neointimal hyperplasia compared with controls. These findings highlight the importance of early initiators of the extrinsic coagulation pathway, especially factor VII and tissue factor, in the response to arterial injury.

Role of leukocytes in neointimal formation after balloon angioplasty in the rabbit atherosclerotic model.

BACKGROUND: Adherence and transendothelial migration of circulating leukocytes is one of the initial events after vascular injury. This process is mediated principally by the expression of integrins (CD11/C18) on the cell surface, which interact with their counterparts in the vessel wall cells. In order to determine the role of leukocytes in the development of neointimal thickening after balloon angioplasty, a monoclonal antibody (R15.7) against leukocyte adherence glycoprotein CD18 was used. METHODS: Femoral artery atherosclerotic lesions were induced in 20 New Zealand White rabbits, which were subjected to balloon angioplasty 28 days thereafter. Twelve hours before and 48 h after balloon angioplasty, 2 mg/kg body weight anti-CD18 or vehicle was randomly injected intravenously. Twenty-one days later the rabbits were killed and morphometric analysis performed. Measurement of functional activity of R15.7 in rabbit sera was performed, analyzing the capacity of the serum sample to inhibit aggregation of JY cells. RESULTS: The serum obtained from monoclonal antibody-treated rabbits showed more than 50% inhibition of cell aggregation at the time of balloon angioplasty. No effect on cell aggregation was seen in the sera of control rabbits. By angiography, there was no difference in lumen diameter and percentage stenosis at follow-up between the two groups. On morphometric analysis, there were no differences in the cross-sectional areas of intima, media, and lumen between the two treatment groups. The percentage cross-sectional area of intima was also similar in the two groups (0.672 +/- 0.04 versus 0.628 +/- 0.04). CONCLUSIONS: Blocking the CD18/CD11 glycoprotein pathway for leukocyte adhesion with a specific monoclonal antibody did not decrease the restenotic process after balloon angioplasty in the atherosclerotic rabbit arterial injury model.

Restenosis after experimental angioplasty. Intimal, medial, and adventitial changes associated with constrictive remodeling.

Predicting and preventing arterial restenosis after angioplasty has failed despite considerable research into mechanisms and techniques. We examined the roles of chronic constriction, neointimal-medial growth, and adventitial changes in restenosis in atherosclerotic rabbits. Angioplasty was performed on femoral artery lesions 4 weeks after lesion induction by air drying and cholesterol-supplemented diet. Angiographic and histological evaluation was conducted 3 to 4 weeks after angioplasty. The angiographic minimum luminal diameter (MLD) increased from 1.31 +/- 0.21 to 1.73 +/- 0.41 mm after angioplasty. Loss in MLD by 3 to 4 weeks was 0.95 +/- 0.64 mm. Initial gain and late loss correlated (P = .008). Late residual stenosis, defined histologically as the difference between the luminal areas of a proximal reference site and lesion site normalized by the luminal area of the reference site, was 52 +/- 32%. Histological indices of chronic constriction, neointimal-medial growth, and adventitial growth were defined on the basis of the areas of these arterial wall layers at the lesion site relative to the reference site. Another parameter defined as the ratio of adventitial area to the area of intima+media at the lesion site allowed evaluation of the relative importance of these layers. Surprisingly, late residual stenosis correlated with chronic constriction (P = .0003) but not with neointimal-medial growth or adventitial growth. The ratio of adventitial area to the area of intima+media at the lesion site also correlated with chronic constriction (P = .01). These findings suggest that factors related to arterial remodeling rather than neointimal-medial growth may dominate the response to angioplasty.

Effects of antisense c-myb oligonucleotides on vascular smooth muscle cell proliferation and response to vessel wall injury.

The process of restenosis after arterial balloon dilatation has been demonstrated to involve smooth muscle cell hyperplasia. Initial reports with antisense oligonucleotides directed against the proto-oncogene c-myb suggest marked in vitro specificity and in vivo efficacy. In the present study, we sought to confirm and extend the hypothesis that antisense to c-myb results in a specific antiproliferative effect with a comprehensive assessment by using different oligonucleotide preparations, different species, and tissue and cellular uptake experiments. Phosphorothioate-protected oligonucleotides representing the appropriate sequence for antisense to c-myb and multiple controls were used to inhibit proliferation of platelet-derived growth factor- and fetal bovine serum-stimulated rat, dog, and human aortic smooth muscle cells in vitro and neointimal proliferation in the rat carotid injury model. In vitro experiments using identical culture conditions in rat, dog, and human aortic smooth muscle cells failed to show specificity as well as consistency in growth inhibitory effects that could be attributed to an antisense mechanism. Proliferation of smooth muscle cell growth in culture was consistently inhibited with oligomers containing a contiguous 4-guanosine residue motif. In vivo, the rat carotid injury neointimal hyperplasia was similar for antisense c-myb (0.095 +/- 0.009 mm2) and sense c-myb (0.090 +/- 0.009 mm2). Fluorescent-labeled oligonucleotides were present in tissue after local delivery via pluronic gel, and their activity rapidly declined over a 72-hour period. Our findings point to the potential nonspecificity and lack of consistency of the antisense oligonucleotide to c-myb in vitro and in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of costs of new atherectomy devices and balloon angioplasty for coronary artery disease.

The in-hospital cost for 126 consecutive patients undergoing 1-vessel, single-lesion coronary atherectomy (atherectomy group) beginning January 1, 1991, was reviewed (65 directional, 44 rotational, and 17 extractional atherectomies), and compared with the cost for 126 consecutive patients matched by sex and age who underwent 1-vessel, single-lesion standard balloon coronary angioplasty (angioplasty group). The in-hospital cost for each patient was determined using charges divided by a correction factor for each hospital department involved. Six different cost fields were created. The overall cost/charge ratio was 0.72. Angiographic and clinical success was 91% and 90% in the angioplasty group and 93% and 90% in the atherectomy group, respectively. Patients who underwent angioplasty required 1.3 +/- 0.6 devices/procedure, as compared with those who underwent atherectomy (2.4 +/- 1 devices/procedure) (p < 0.0001). The mean cost of angioplasty was $7,301 +/- $4,637 and of atherectomy devices $9,345 +/- $8,856 (28% increase). The difference was principally related to an increase in cost of supplies: angioplasty $2,028 +/- $1,196 versus atherectomy $3,632 +/- $1,525 (79% increase). There were no significant differences in hospitalization cost, procedure-room cost, and pharmacy and laboratory costs. Thus, higher risk morphologic lesions can be approached with new atherectomy devices with clinical and complication rates similar to coronary angioplasty. However, these results were obtained at a 28% increase in cost.

Local delivery of dexamethasone for prevention of neointimal proliferation in a rat model of balloon angioplasty.

A periadventitial polymer system is an alternative local drug delivery technique to obtain and maintain high tissue levels of the drug at the site of vascular injury. To determine if local periadventitial delivery of dexamethasone decreases neointimal proliferation after balloon vascular injury, in three groups of Sprague-Dawley rats, 5% dexamethasone, 0.5% dexamethasone, and placebo silicone polymers were implanted around the left common carotid artery after balloon injury. In a fourth group, placebo polymers were implanted without balloon injury. Dexamethasone serum and tissue levels after polymer implantation were significantly higher in the 5% dexamethasone group compared with the 0.5% dexamethasone group. There was no neointima formation in any of the arterial segments covered with placebo polymers for 3 wk, but without balloon injury. In the arterial segments covered by the 5 and 0.5% dexamethasone polymers, there was a 76 and 75% reduction in intima/media ratios, respectively, compared with the placebo group (5% dexamethasone, 0.26 +/- 0.04; 0.5% dexamethasone, 0.27 +/- 0.03; placebo, 1.09 +/- 0.16, respectively; P < 0.0001). These results suggest that: (a) silicone polymers wrapped around the common carotid arteries for 3 wk did not, without balloon injury, stimulate neointimal proliferation in the rat model; (b) the activity of the drug-eluting polymer for suppressing intimal proliferation was chiefly, but not exclusively, site specific; and (c) transadventitial local delivery of dexamethasone at two different doses markedly inhibits neointimal proliferation after balloon vascular injury.