Active or passive bio-coating: does it matters in extracorporeal circulation?

BACKGROUND: Two types of surface coating for cardiopulmonary bypass (CPB) are used: bioactive (heparin, nitric oxide) and biopassive (albumin, polyethyleneoxide (PEO), phosphorylcholine). When haemocompatible coatings are combined with the separation of pleuro-pericardial aspiration, attenuation of both the coagulation and complement cascades, as well as better platelet preservation, has been demonstrated. This study wants to investigate if the combination of a bioactive with a biopassive coating (unfractionated heparin embedded in a phosphorylcholine matrix) combines the beneficial effects of both approaches. MATERIALS AND METHODS: Thirty patients undergoing elective CABG were prospectively randomized into two groups of 15 patients. The sole exclusion criterion was an ejection fraction of less than 40%. In the control group (PC), the whole CPB circuit was coated with phosphorylcholine (PC). In the study group (XPC), unfractionated heparin was embedded in the PC matrix of the oxygenator and arterial line filter. RESULTS: No differences were found for haemolytic index, thrombin-anti-thrombin complex (TAT), IL-6, IL-10 and blood loss. PF4 plasma concentration increased from 27.6±22.0 IU/mL to 165.7±43.9 IU/mL (p<0.001) at 15 minutes of CPB in the PC and from 16.0±9.7 IU/mL to 150.9 ± 61.3 IU/mL (p<0.001) in the XPC group. Terminal complement complex (TCC) increased over time in both groups until the end of CPB (Figure 2A). Within each group, TCC generation was statistically significantly higher after the release of the aortic cross-clamp (p<0.001) and at the end of CPB (p<0.001). Total TCC generation was statistically significantly higher in the XPC group compared to the PC group (p=0.026). The difference was statistically significant after the release of the aortic cross-clamp (p=0.005) and at the end of CPB (p=0.001). CONCLUSIONS: Based on our results, there is no additional benefit in combining phosphorylcholine with unfractionated heparin in elective patients undergoing coronary artery bypass grafting (CABG). Massive haemodilution leads to enhanced complement activation.

Correction of diabetic nod mice with insulinomas implanted within Baxter immunoisolation devices.

Insulin replacement by injection is clearly not a cure for Insulin Dependent Diabetes Mellitus (IDDM). Replacement of the destroyed islets by pancreas or islet allograft transplantation can achieve the good metabolic control required to prevent diabetic complications, but tissue supply is limited. The problem of islet supply to treat the 1 million IDDM patients in the USA could be overcome by using immortalized islet beta-cells as a donor source. However, before either allogeneic or xenogeneic immortalized beta-cells are used, some major problems have to be overcome: control of immortalized cell growth, allograft or xenograft rejection and recurrence of autoimmunity. To tackle these problems we have used a cell impermeable immunoisolation device containing mouse insulinoma cells. Transplantation of devices with insulinomas from NOD mice carrying the Rat-insulin promoter regulated SV40 T-Antigen transgene (RIP-TAg), normalized the blood glucose levels of diabetic NOD mice. Insulinomas from allogeneic CBA/NOD-RIP-TAg mice were also capable of normalizing diabetic NOD mice. Not only were non-fasting blood glucoses normalized but when given an intraperitoneal injection of glucose, the corrected mice had a near normal clearance of glucose from the blood. When the devices were removed from normalized mice they became diabetic again, demonstrating that the immunoisolation device was capable of protecting against both alloimmune and autoimmune destruction. The results with allogeneic mouse beta-cells suggest the possibility that immortalized human beta-cells could be an effective source of tissue to correct diabetes in IDDM patients without the use of immunosuppression.

Population pharmacokinetic analysis of pegylated interferon alfa-2b and interferon alfa-2b in patients with chronic hepatitis C.

BACKGROUND: This study quantified pharmacokinetic changes in pegylated and nonpegylated interferon alfa-2b during 48 weeks of treatment and the influences of covariates on the basis of sparsely sampled serum concentrations and activity values. Possible relationships between pharmacokinetic and pharmacodynamic variables were investigated. METHODS: Patients with chronic hepatitis C were enrolled in a clinical trial that compared the efficacy of pegylated interferon alfa-2b with interferon alfa-2b. Single blood samples were obtained from each patient at weeks 4, 12, 24, 36, and 48. Three pharmacostatistical models were developed for 2 immunoassays and 1 bioassay. RESULTS: Apparent clearance values of pegylated interferon alfa-2b and interferon alfa-2b at the end of treatment declined 33.7% and 80.0%, respectively, from their week 4 values. Bioactivity increased 41% to 58% at week 48 for different treatment groups. Changes were greatest in the first weeks of administration and diminished during the subsequent months. Body weight had a modest positive effect on clearance values and activity. Within each dose level, no significant associations were observed between pharmacokinetic variables and any pharmacodynamic variables (hepatitis C virus--RNA responses or changes in neutrophils and platelets). CONCLUSIONS: This analysis confirms earlier observations of progressive pharmacokinetic changes in the patients with hepatitis C during 48 weeks of treatment. The absence of a relationship between toxicity or efficacy variables and interferon concentration or activity (within a dose level) suggests that clinical management of patients (eg, for efficacy or to manage toxicity) should be based on clinically derived dosing guidelines rather than on serum concentration or activity criteria.

Pegylated interferon-alpha2b: pharmacokinetics, pharmacodynamics, safety, and preliminary efficacy data. Hepatitis C Intervention Therapy Group.

AIMS: The objectives of this study were to assess the safety, pharmacokinetic and pharmacodynamic profiles, and antiviral efficacy of pegylated interferon-alpha2b monotherapy in patients with chronic hepatitis C. METHODS: Fifty-eight patients (38 men, 20 women; age range, 25 to 65 years) with compensated chronic hepatitis C were enrolled in this open-label, randomized, active controlled study. Patients received 0.035 to 2.0 microg/kg pegylated interferon-alpha2b subcutaneously weekly or the active control, interferon-alpha2b 3 million IU subcutaneously three times/week, for 24 weeks. Safety and antiviral efficacy assessments were performed during treatment and in a subsequent 4-week follow-up period. Detailed pharmacokinetic assessments were performed at weeks 1 and 4. RESULTS: Pegylated interferon-alpha2b produced dose-related reductions in white blood cells, neutrophils, and platelets, and dose-related increases in oral temperature, serum neopterin, and serum 2'5'-oligoadenylate synthetase activity, which were qualitatively similar to those produced by nonpegylated interferon-alpha2b. Reported adverse events (flu-like symptoms, asthenia) were qualitatively similar in pegylated interferon-alpha2b- and nonpegylated interferon-alpha2b-treated groups. Dose-related antiviral activity, as measured by loss of detectable serum hepatitis C virus RNA (<100 copies/mL), was noted at the end of treatment and after 4 weeks of follow-up. Both pegylated and nonpegylated interferon-alpha2b were rapidly absorbed, with maximal concentrations occurring approximately 8 to 12 hours after dose administration. Pegylated interferon-alpha2b had sustained maximal serum concentrations for 48 to 72 hours after dose administration, whereas nonpegylated interferon-alpha2b concentrations declined rapidly. Volume of distribution for both compounds was similar (approximately 1 L/kg). Pegylated interferon-alpha2b elimination half-life was approximately 10-fold greater, and mean apparent clearance was one tenth that of nonpegylated interferon-alpha2b. CONCLUSIONS: Pegylated and nonpegylated interferon-alpha2b safety and pharmacodynamic profiles were comparable. Pegylated interferon-alpha2b demonstrated delayed clearance compared with nonpegylated interferon-alpha2b, consistent with once-weekly administration.

Detection and characterization of antibodies to PEG-IFN-alpha2b using surface plasmon resonance.

Some patients treated with type I interferon (IFN) preparations develop neutralizing antibodies that may abrogate any clinical benefit. We have a new complex of polyethylene glycol12000 and IFN-alpha2b (PEG-IFN-alpha2b) in clinical trials and need to be able to detect any antibodies formed specifically against the complex. We have, therefore, devised a method based on measurement of surface plasmon resonance (SPR) in the BIACORE 2000 apparatus. PEG-IFN-alpha2b is anchored to one flow cell on the sensor chip, IFN-alpha2b to another, and PEG to a third. A 20 microl serum sample flows in turn through the three cells, which are optically scanned. Any antibodies in the serum bind to the corresponding immobilized antigen, and a change in the optical signal is generated. With appropriate specific reagents, their immunoglobulin isotype can be similarly established. The automated assay can quickly test numerous sera. Very little serum is needed, and the assay is reliable and precise and can detect low-alphaffinity antibodies.

Structural and biologic characterization of pegylated recombinant IFN-alpha2b.

The type I interferon-alpha (IFN-alpha) family is a family of natural small proteins that have clinically important anti-infective and antitumor activity. We have developed a semisynthetic protein-polymer conjugate of IFN-alpha2b (Intron A) by attaching a 12,000-Da monomethoxypolyethylene glycol (PEG-12000) polymer to the protein. PEG conjugation is thought to increase the serum half-life and thereby prolong patient exposure to IFN-alpha2b without altering the biologic potency to the protein. Matrix-assisted laser desorption ionization/mass spectrometry (MALDI-MS), high-performance size exclusion chromatography (HPSEC), circular dichroism (CD) analysis and tryptic digestion peptide analysis of PEG Intron demonstrated that the IFN-alpha2b protein was approximately 95% monopegylated and that the primary, the secondary, and the tertiary structures were unaltered. Pegylation did not affect the epitope recognition of antibodies used for Intron A quantitation. An extensive analysis of the pegylated positional isomers revealed that approximately 50% of PEG Intron was monopegylated on the His(34) residue of the IFN-alpha2b protein. The highest antiviral activity of the pegylated positional isomers for PEG Intron was associated with the His(34) pegylated isomer. The specific activity for PEG Intron in an antiviral cytopathic protection assay was 28%, relative to Intron A. However, the potency of PEG Intron, defined as bioactivity independent of protein concentration, was comparable to Intron A at both the molecular and cellular levels in a battery of in vitro assays. Equivalent units of PEG Intron and Intron A were indistinguishable for the induction of several key IFN-induced genes, including 2',5'-oligoadenylate synthetase (2',5'-OAS) and protein kinase R (PKR), in Molt 4 cells. The antiviral dose-response curves revealed that there were no significant differences between PEG Intron and Intron A. This demonstrated that the introduction of more IFN-alpha2b protein associated with equivalent unit dosing of PEG Intron did not create any antagonism or agonism in the antiviral assay. In assays for the immune response, PEG Intron and Intron A displayed comparable potency for both natural-killer (NK) and lymphokine-activated killer (LAK) cell cytolytic activity and for the induction of class I major histocompatibility protein. These results demonstrate that PEG Intron maintains an in vitro biologic potency profile for both antiviral and immunotherapeutic activity that is highly comparable to that of Intron A.

Relative anti-caries efficacy of 1100, 1700, 2200, and 2800 ppm fluoride ion in a sodium fluoride dentifrice over 1 year.

There is limited evidence from clinical trials on the dose response of sodium fluoride dentifrices at concentrations above 1100 ppm fluoride ion, with respect to caries efficacy. This randomized, double-blind study examined the anti-caries effectiveness of sodium fluoride dentifrices containing 1700 ppm, 2200 ppm and 2800 ppm fluoride ion relative to an 1100 ppm fluoride ion control. A population of 5439 elementary schoolchildren, aged 6-15 years, was recruited from an urban central Ohio area with a low fluoride content water supply (<0.3 ppm). Subjects were examined by visual-tactile and radiographic examination at baseline and after 1, 2, and 3 years of using the sodium fluoride dentifrices. Subjects were stratified according to gender, age and baseline DMFS scores derived from the visual-tactile baseline examination and randomly assigned to one of four treatment groups: 0.243% sodium fluoride (1100 ppm fluoride ion), 0.376% sodium fluoride (1700 ppm fluoride ion), 0.486% sodium fluoride (2200 ppm fluoride ion), and 0.619% sodium fluoride (2800 ppm fluoride ion). All products were formulated with the same fluoride compatible silica abrasive. Results after 1 year provided evidence of a positive sodium fluoride dose response. Compared to the 1100 ppm fluoride treatment group, the 1700 ppm fluoride treatment group had an 11.0% reduction in DMFS that was not statistically significant, while the 2200 ppm and 2800 ppm fluoride treatment groups showed statistically significant (P<0.05) reductions of 18.6% and 20.4%, respectively. The reductions in caries delivered by the higher fluoride dentifrices were present across all tooth surface types, but were most pronounced for occlusal surfaces. Results at years 2 and 3 were confounded by a concurrent fluoride rinse program, which involved portions of the study population. While the trends for the higher fluoride dentifrices observed at year 1 remained at years 2 and 3, the difference observed between treatments were substantially less and failed to reach statistical significance (P<0.05). Collectively, the data demonstrate that the 2200 ppm and the 2800 ppm fluoride treatments delivered statistically significantly greater caries efficacy than the 1100 ppm fluoride treatment. This large-scale clinical trial provides evidence of a positive statistically significant dose relationship between dental caries and sodium fluoride in a dentifrice at levels above 1100 ppm fluoride at year 1.

Palatally impacted canines: aetiology of impaction and the scope for interception. Report of cases outside the guidelines for interception.

Patients with palatally impacted canines have an increased incidence of missing or anomalous lateral incisors adjacent to the impacted canines. Their arches are often uncrowded and this, in part, is linked to the increased incidence of missing or anomalous lateral incisors. Other teeth are also more frequently missing. The present guidelines for the relief of palatally impacted canines by extraction of the deciduous canine require that the patient is aged between 10-13 years and that normal space conditions are present. Two successful case reports are presented which were outside the recommended guidelines. The technique of relieving a palatal impaction by extraction of the deciduous canine has wide application.

Reducing the incidence of palatally impacted maxillary canines by extraction of deciduous canines: a useful preventive/interceptive orthodontic procedure. Case reports.

The early detection of palatally impacted permanent maxillary canines is stressed. Appropriate radiographs to determine impactions are suggested and removal of deciduous canines to eliminate impactions in patients who have good dental arches with no space deficiency is recommended. Two case histories are presented to illustrate the method.

The impacted maxillary canine. Further observations on aetiology, radiographic localization, prevention/interception of impaction, and when to suspect impaction.

Adjacent anomalous or missing maxillary lateral incisors have been implicated in the aetiology of palatally displaced canines by not providing proper guidance to the canine during its eruption. However, a recent review of the literature suggests that the aetiology of palatally displaced canines is genetic in origin. The aetiology of labially impacted canines differs, being due to inadequate arch space. Vertex occlusal radiographs have been recommended for localization but have limitations, and a case is illustrated where this radiograph is deceptive. The prevention/interception of a palatally displaced canine by the extraction of the deciduous canine is best carried out as early as the displacement is detected, mostly soon after 10 years of age. Usually, prevention/interception will avoid the surgical and orthodontic treatment needed to align a palatally impacted canine and may help prevent resorption of the adjacent incisor root. Suspicions that an impaction could occur or has occurred arise a) before the age of 10 years if there is a familial history and/or the maxillary lateral incisors are anomalous or missing; b) after the age of 10 years if there is asymmetry in palpation or a pronounced difference in eruption of canines between the left and right side; or the canines cannot be palpated and occlusal development is advanced; or, the lateral incisor is proclined and tipped distally; and, on a panoramic radiograph of the late mixed dentition if the incisal up of the canine overlaps the root of the lateral incisor.

Reducing the incidence of unerupted palatally displaced canines by extraction of deciduous canines. The history and application of this procedure with some case reports.

The procedure of extracting the deciduous canine to reduce the incidence of the unerupted palatally displaced canine was first described in 1951, and an article solely devoted to the technique appeared in 1959. The procedure then virtually vanished until 1981. A prospective study published in 1988 created the first widespread interest in the method which now appears in major texts. Why the procedure succeeds is uncertain. In the 1950s non-resorption of the deciduous canine was thought to cause palatal deflection of its successor and therefore it appeared appropriate to extract the obstructing deciduous tooth. It has been estimated that the technique should be successful in approximately one in three of all cases in the population aged 10 to 13 years. The earlier the detection the better the prognosis, because the unerupted canine frequently moves more mesially with time. Before the procedure is attempted it is important to discuss possible outcomes with the patient. Three successfully treated cases are illustrated. The first conformed with the guidelines of having an uncrowded maxillary arch and being aged between 10 and 13 years. The second was aged 15 years 2 months at commencement. An unsuccessful surgical exposure of the permanent canines followed by extraction of the deciduous canines was carried out in the third case.

Treatment planning in orthodontics and orthognathic surgery: the significance of tooth inclination and dental compensations.

The scope of orthodontic treatment is examined and the importance of the initial tooth inclinations and skeletal base relationships is explained. Dental compensations which occur in all three planes of space are discussed. Special attention is given to the importance of dental compensations in the antero-posterior plane in orthognathic surgery treatment planning. There is a necessity for early definitive decision-making in the borderline orthognathic surgery patient and the role of orthodontic camouflage is pointed out. Case selection for treatment with removable appliances is explored.

Teeth in cross-bite: the role of removable appliances.

The role of removable appliances with springs for the treatment of teeth in anterior and posterior cross-bite is discussed. The indications for their use (that is, case selection), and their manipulation are examined. Cases are presented where removable appliances are the appliances of choice in the first stage of the correction of a posterior cross-bite, the final treatment being completed with fixed appliances. The ease of correcting and retaining various maxillary teeth which may be in cross-bite is discussed.

Reduction in dental caries with four concentrations of sodium fluoride in a dentifrice: a meta-analysis evaluation.

Information on the effects of fluoride concentrations above 1,100 ppm in dentifrices is not extensive in the literature. The objective of this meta-analysis was to examine and compare the anticaries effectiveness (in terms of DMFS scores) of 1,700 ppm, 2,200 ppm and 2,800 ppm F- ion (as sodium fluoride) dentifrices vs. an 1,100 ppm F- ion (as sodium fluoride) control dentifrice based on results from six double-blind, randomized clinical studies, each conducted over a two- to three-year period. The studies each enrolled approximately 1,200-2,000 male and female school children per treatment group in grades I through 8, and were conducted in areas with low fluoride content water supplies in the states of Indiana, Pennsylvania, Ohio and Oregon. Separate meta-analyses were performed on the study results (DMFS increment scores determined by visual-tactile examinations supplemented with radiographs) for the one-year, two-year and three-year examinations. Comparisons of the 1,700 ppm F-, 2,200 ppm F-, and 2,800 ppm F- groups vs. the 1,100 ppm F- group were based on pooling the effect sizes for these comparisons from the individual studies. The effect sizes were calculated in two different ways, reflecting the analyses that were performed in the original studies: 1) effects based on the sample means and variances; and 2) effects based on the adjusted sample means and mean squared error from an analysis of covariance. The results obtained from this meta-analysis provide evidence that the use of a 2,800 ppm F- ion, as sodium fluoride, dentifrice results in statistically significantly lower caries increment than the use of an 1,100 ppm F- ion, as sodium fluoride, dentifrice. This result was noted after one, two, and three years of dentifrice use. The 1,700 ppm F- and 2,200 ppm F- dentifrice groups showed some directional advantages over the 1,100 ppm F- dentifrice group, however the analysis did not establish these groups as statistically significantly better than 1,100 ppm F-. The meta-analysis based on analysis of covariance results was somewhat more sensitive to treatment group differences than the analysis based on sample means and variances, as was expected.

Localisation of the unerupted maxillary canine: additional observations.

Occlusal radiographs are recommended for the tube shift method used to localise the unerupted maxillary canine. Several case histories are presented to explore how diagnostic occlusal films may be obtained. The initial maxillary incisor inclination determines the vertical angulation of the tube, while the mesio-distal position of the canine crown determines the horizontal angulation of the tube to the mid-sagittal plane. Increased distances aid localisation: both the distance between the impacted tooth and its reference tooth, and the distance between the positions of the tube at exposure are significant. If an orthopantomogram and an occlusal film are to be taken as initial radiographs, the orthopantomogram should be read first to determine the position of the tube for the occlusal film. Radiographs taken previously may provide information on centring the tube for the occlusal film. The horizontal tube shift between two occlusal films is a more sensitive means of localising canines than is the vertical tube shift available between an orthopantomogram and an occlusal film.

The treatment of traumatized permanent anterior teeth: case report & literature review. Part I--Management of intruded incisors.

A case is reported in which an intruded incisor was initially treated by an endodontic dressing with calcium hydroxide and then extruded using a removable orthodontic appliance. A follow-up examination seven years after completion of endodontic therapy and bleaching showed a favourable response. A review of the relevant literature indicates that intrusion occurs in five to twelve per cent of luxation cases. In this type of injury maximum damage occurs to the pulp and all supporting structures because the tooth is driven into the alveolar process. Complications which have been reported include: pulp necrosis, apical radiolucencies, partial or total pulp calcification, root resorption (surface, inflammatory or replacement), marginal periodontal bone breakdown, and arrested or disturbed root development. The prognosis for pulp survival after intrusion is much more favourable for teeth with incomplete root formation than for teeth with complete root formation. Treatment options available to bring an intruded tooth into alignment are: to await spontaneous re-eruption which may occur if root formation is incomplete, uncovering of the intruded crown, orthodontic extrusion which is allied with gentle luxation if the tooth does not move, and immediate surgical repositioning.

Intracoronal radiolucencies in unerupted teeth of orthodontic patients: three case reports.

Three cases of intracoronal radiolucencies in unerupted teeth are reported. The aetiology and treatment of this condition which may first be detected by the orthodontist are discussed. In extreme cases, involved teeth may be lost.

Ankylosis of permanent teeth: a case report and literature review.

A case report describing an ankylosed permanent maxillary canine which was brought into the arch by a combination of surgery and orthodontics is used as a basis to review the literature concerning many aspects of the management of ankylosed permanent teeth. The literature indicates surgical luxation is a two edged sword, that is, it may cause ankylosis if used with surgical exposures but it can also be the only means of treating ankylosis. The treatment of the canine which is the subject of this case report resulted in damage to the tooth. Vanarsdall's recent contributions in this field are detailed.

Endovascular treatment of ruptured brain AVMs in the acute phase of hemorrhage.

BACKGROUND AND PURPOSE: Patients with ruptured brain AVMs are at considerable risk of repeat hemorrhage, particularly when associated intranidal or flow-related aneurysms are present. There is controversy about the timing of diagnosis and treatment of patients with hemorrhagic stroke. We present our results of endovascular treatment of ruptured AVMs in the acute phase. MATERIALS AND METHODS: Between January 2008 and March 2011, 23 patients (16 men, 7 women; mean age 42 years) with AVM-related hemorrhagic stroke were treated with endovascular techniques within 10 days of the ictus. There were 10 micro-AVMs (< 1 cm) and 1 single-hole pial fistula. In 9 patients, an intranidal or flow-related aneurysm was the likely cause of hemorrhage. RESULTS: Complete obliteration of the AVM with Onyx was achieved in 13 of 23 patients (57%). Eight of the 13 AVMs were micro-AVMs and 3 had an intranidal aneurysm. Partial obliteration of the AVM was achieved in 10 of 23 patients (43%). In 6 of these 10 patients, an intranidal (n = 1) or flow-related aneurysm (n = 5) was obliterated with Onyx or coils. There were no complications of treatment. During a mean follow-up of 21 months in 22 surviving patients, no repeat hemorrhage occurred. CONCLUSIONS: Endovascular treatment with Onyx in the acute phase cured most ruptured AVMs. All 9 AVM-associated aneurysms that were considered the source of hemorrhage could be excluded from the circulation. In patients with AVM-related hemorrhagic stroke, prompt angiographic diagnosis and treatment may improve prognosis by reducing repeat hemorrhage rate.

Curative embolization of brain arteriovenous malformations with onyx: patient selection, embolization technique, and results.

BACKGROUND AND PURPOSE: A new curative embolization technique with Onyx for selected small and medium-sized superficially located brain AVMs was developed, which consists of obliteration of the nidus, including incremental occlusion of the draining veins. We report our first clinical results. MATERIALS AND METHODS: Between June 2008 and July 2011, 24 patients (7 women, 17 men; mean age, 41 years; range, 6-74 years) with AVMs were selected for curative embolization with Onyx. Presentation was hemorrhage in 14 and seizures in 10 patients. AVM location was frontal in 11, occipital in 6, parietal in 4, and temporal in 3. AVM size was a mean of 2.2 cm (median, 2; range, 1-3 cm). RESULTS: Complete angiographic obliteration of the AVM with Onyx in a single session was achieved in all 24 patients. There were no hemorrhagic or ischemic complications (0%; 95% CI, 0%-16.3%), and no new deficits induced by the treatment. Of 14 patients with ruptured AVMs, 1 patient who presented with a large frontal hematoma died shortly after surgical evacuation of the hematoma following complete embolization of a micro-AVM. Follow-up angiography at 3 months in 23 patients demonstrated a small AVM remnant in 1 that was treated with gamma knife radiosurgery. The other 22 AVMs remained completely occluded. CONCLUSIONS: In selected patients with small and medium-sized superficial brain AVMs, as defined in our study, injection of Onyx by using a curative embolization technique in a single session seems to provide a safe and effective alternative to radiosurgery or surgery.