Effects of music therapy on mood, pain, and satisfaction in the neurologic inpatient setting.

PURPOSE: Music therapy (MT) has been used in health care settings for a wide variety of treatment goals. Many inpatients with neurologic impairments struggle with low mood and pain for which MT may be a novel adjunct treatment. The aims of this study were to: (1) evaluate change in mood and pain following a single MT session; (2) explore the impact of an MT program on mood, pain and satisfaction from the perspective of the patient, family and staff. MATERIALS AND METHODS: A mixed-methods study was conducted. Forty participants completed pre/post MT surveys evaluating mood, pain and satisfaction. Individual semi-structured interviews and focus groups were conducted with 14 MT program participants (inpatients), 5 family members of participants and 16 staff. RESULTS: There was significant improvement in mood (p < 0.001) and decrease in pain (p < 0.05) from pre-to-post MT with 74% reporting being "very satisfied" with the session. "Benefits of MT" was the overarching theme of the qualitative data. Subthemes were emotional regulation, pain management, effects on self-concept, enjoyment, and social connectedness. CONCLUSIONS: Improvements in mood and pain were reported from pre-to-post MT session and in interviews. Further evaluation of MT effectiveness against standard of care rehabilitation and cost implications is required.Implications for RehabilitationMusic therapy (MT) is delivered by accredited music therapists (MTAs) in health care settings, including rehabilitation units, as an individual, group or co-treatment therapy.MT can be used for a range of health outcomes, including the treatment of mood and pain, in addition to improving inpatient satisfaction.Early evidence using pre/post MT surveys suggests an improvement in mood and pain following a single therapy session.Qualitative data suggest overall benefit of offering MT services in addition to standard neurorehabilitation therapy, including improvements to emotional regulation, pain management, self-concept, enjoyment, and social connectedness.

Response to comment on "Evidence of prehistoric human activity in the Falkland Islands".

Hamley et al. previously presented multiple lines of evidence that people were present in the Falkland Islands before Europeans and may have brought the now-extinct canid, Dusicyon australis. Stable isotope data reported by Clark et al. indicate that D. australis had a high-trophic, marine diet that terrestrialized following European arrival. This is consistent with our hypothesis of a human mutualism.

Evidence of prehistoric human activity in the Falkland Islands.

When Darwin visited the Falkland Islands in 1833, he noted the puzzling occurrence of the islands' sole terrestrial mammal, Dusicyon australis (or "warrah"). The warrah's origins have been debated, and prehistoric human transport was previously rejected because of a lack of evidence of pre-European human activity in the Falkland Islands. We report several lines of evidence indicating that humans were present in the Falkland Islands centuries before Europeans, including (i) an abrupt increase in fire activity, (ii) deposits of mixed marine vertebrates that predate European exploration by centuries, and (iii) a surface-find projectile point made of local quartzite. Dietary evidence from D. australis remains further supports a potential mutualism with humans. The findings from our study are consistent with the culture of the Yaghan (Yámana) people from Tierra del Fuego. If people reached the Falkland Islands centuries before European colonization, this reopens the possibility of human introduction of the warrah.

Effectiveness of a Delirium Prevention Initiative on an Inpatient Neuroscience Unit.

ABSTRACT: BACKGROUND: Delirium frequently develops in hospitalized patients and results in increased mortality, longer length of stay, and need for transitional care. Neurological patients are at an increased risk for developing delirium. There is a paucity of research on effective prevention strategies for this population. PURPOSE: The objectives of this project were to improve nurses' knowledge and confidence in delirium prevention, design a delirium volunteer program, and establish ongoing monitoring for continued improvement. METHODS: This study is a quality improvement project using a pretest-posttest design to examine the benefits of refocusing care from delirium management to delirium prevention. The sample included 304 patients pre and 332 post intervention. The interventions included delirium education for nurses and the recruitment of trained volunteers to implement nonpharmacological, multicomponent delirium prevention interventions. RESULTS: Forty-eight nurses completed delirium education, and 11 volunteers were recruited and trained. There was a significant increase in nursing knowledge (z = 3.967, P < .0005) and confidence (z = 3.989, P < .0005). Volunteers visited 54 patients and implemented 99 interventions post implementation. CONCLUSION: This pre-post improvement project provides beginning evidence that nursing education increased nurses' knowledge and confidence in preventing and treating delirium. Trained volunteers supported using nonpharmacological delirium prevention interventions, but ongoing evaluation is needed to determine the impact of volunteers on delirium rates.

Toward a better understanding of the mechanism of action for intra-arterial delivery of irinotecan from DC Bead(TM) (DEBIRI).

DC Bead is designed for the embolization of liver malignancies combined with local sustained chemotherapy delivery. It was first demonstrated around a decade ago that irinotecan could be loaded into DC Bead and used in a transarterially directed procedure to treat colorectal liver metastases, commonly referred to as drug-eluting bead with irinotecan (DEBIRI). Despite numerous reports of its safe and effective use in treating colorectal liver metastases patients, there remains a perceived fundamental paradox as to how this treatment works. This review of the mechanism of action of DEBIRI provides a rationale for why intra-arterial delivery of this prodrug from an embolic bead provides for enhanced tumor selectivity, sparing the normal liver while reducing adverse side effects associated with the irinotecan therapy.

Toenail mercury Levels are associated with amyotrophic lateral sclerosis risk.

INTRODUCTION: Mercury is a neurotoxic metal that is potentially a risk factor for amyotrophic lateral sclerosis (ALS). Consumption of methylmercury contaminated fish is the primary source of US population exposure to mercury. METHODS: We used inductively coupled plasma mass spectrometry to measure levels of mercury in toenail samples from patients with ALS (n = 46) and from controls (n = 66) as a biomarker of mercury exposure. RESULTS: Patients with ALS had higher toenail mercury levels (odds ratio 2.49, 95% confidence interval 1.18-5.80, P = 0.024) compared with controls, adjusted for age and sex. We also estimated the amount of mercury consumed from finfish and shellfish and found toenail mercury levels elevated overall among patients with ALS and controls in the top quartile for consumption (P = 0.018). DISCUSSION: Biomarker data show that ALS is associated with increased with mercury levels, which were related to estimated methylmercury intake via fish. Replication of these associations in additional populations is warranted. Muscle Nerve, 2018.

DC BeadM1™: towards an optimal transcatheter hepatic tumour therapy.

Clinical use of DC Bead™ loaded with doxorubicin (DEBDOX™) or irinotecan (DEBIRI™), for the treatment of primary and secondary tumours of the liver respectively, is showing great promise. Recently there has been a tendency to select smaller bead size ranges to treat tumours in an effort to allow more drug dose to be administered, improve tumoural penetration and resultant drug delivery and tumour coverage. Herein we describe the development and performance characterisation of a new DC Bead size range (DC BeadM1 (TM), 70-150 µm) capable of an increased bead delivery in the distal vasculature, corresponding to greater tumour coverage and drug dose delivered. Both unloaded and drug loaded DC BeadM1 were shown to have a greater density of distal volume of penetration although the ultimate distal level of penetration was the same as that of the 100-300 µm beads in an in vitro penetration model. Elution of doxorubicin was slower than irinotecan elution, but it was similar when comparing the same drug elution from 70 to 150 µm compared to 100-300 µm beads. Radiopaque versions of 70-150 and 100-300 µm beads were prepared in order to evaluate distribution ex vivo using µ-CT and doxorubicin distribution using epifluorescent microscopy. Liver distribution of the radiopaque versions of the beads was shown to be more distal and efficient at filling smaller vessels with the DC BeadM1 and correspondingly more beads were found per vessel histologically with a larger area of drug coverage with the smaller size range. This study indicates that the smaller (70-150 µm) beads should permit an increased dose of drug to be administered to both hypervascular and hypovascular tumours as compared to 100-300 µm beads.

Younger Dryas deglaciation of Scotland driven by warming summers.

The Younger Dryas Stadial (YDS; ∼ 12,900-11,600 y ago) in the Northern Hemisphere is classically defined by abrupt cooling and renewed glaciation during the last glacial-interglacial transition. Although this event involved a global reorganization of atmospheric and oceanic circulation [Denton GH, Alley RB, Comer GC, Broecker WS (2005) Quat Sci Rev 24:1159-1182], the magnitude, seasonality, and geographical footprint of YDS cooling remain unresolved and pose a challenge to our understanding of abrupt climate change. Here, we present a deglacial chronology from Scotland, immediately downwind of the North Atlantic Ocean, indicating that the Scottish ice cap disintegrated during the first half of the YDS. We suggest that stratification of the North Atlantic Ocean resulted in amplified seasonality that, paradoxically, stimulated a severe wintertime climate while promoting warming summers through solar heating of the mixed layer. This latter process drove deglaciation of downwind landmasses to completion well before the end of the YDS.

Rapid increase in southern elephant seal genetic diversity after a founder event.

Genetic diversity provides the raw material for populations to respond to changing environmental conditions. The evolution of diversity within populations is based on the accumulation of mutations and their retention or loss through selection and genetic drift, while migration can also introduce new variation. However, the extent to which population growth and sustained large population size can lead to rapid and significant increases in diversity has not been widely investigated. Here, we assess this empirically by applying approximate Bayesian computation to a novel ancient DNA dataset that spans the life of a southern elephant seal (Mirounga leonina) population, from initial founding approximately 7000 years ago to eventual extinction within the past millennium. We find that rapid population growth and sustained large population size can explain substantial increases in population genetic diversity over a period of several hundred generations, subsequently lost when the population went to extinction. Results suggest that the impact of diversity introduced through migration was relatively minor. We thus demonstrate, by examining genetic diversity across the life of a population, that environmental change could generate the raw material for adaptive evolution over a very short evolutionary time scale through rapid establishment of a large, stable population.

Histidine kinase activity of the ethylene receptor ETR1 facilitates the ethylene response in Arabidopsis.

In Arabidopsis (Arabidopsis thaliana), ethylene is perceived by a receptor family consisting of five members. Subfamily 1 members ETHYLENE RESPONSE1 (ETR1) and ETHYLENE RESPONSE SENSOR1 (ERS1) have histidine kinase activity, unlike the subfamily 2 members ETR2, ERS2, and ETHYLENE INSENSITIVE4 (EIN4), which lack amino acid residues critical for this enzymatic activity. To resolve the role of histidine kinase activity in signaling by the receptors, we transformed an etr1-9;ers1-3 double mutant with wild-type and kinase-inactive versions of the receptor ETR1. Both wild-type and kinase-inactive ETR1 rescue the constitutive ethylene-response phenotype of etr1-9;ers1-3, restoring normal growth to the mutant in air. However, the lines carrying kinase-inactive ETR1 exhibit reduced sensitivity to ethylene based on several growth response assays. Microarray and real-time polymerase chain reaction analyses of gene expression support a role for histidine kinase activity in eliciting the ethylene response. In addition, protein levels of the Raf-like kinase CONSTITUTIVE TRIPLE RESPONSE1 (CTR1), which physically associates with the ethylene receptor ETR1, are less responsive to ethylene in lines containing kinase-inactive ETR1. These data indicate that the histidine kinase activity of ETR1 is not required for but plays a modulating role in the regulation of ethylene responses. Models for how enzymatic and nonenzymatic regulation may facilitate signaling from the ethylene receptors are discussed.

Cultivable bacteria from ancient algal mats from the McMurdo Dry Valleys, Antarctica.

The McMurdo Dry Valleys in Antarctica are a favorable location for preservation of dormant microbes due to their persistent cold and dry climate. In this study, we examined cultivable bacteria in a series of algal mat samples ranging from 8 to 26539 years old. Cultivable bacteria were found in all samples except one (12303 years old), but abundance and diversity of cultivable bacteria decreased with increasing sample age. Only members of the Actinobacteria, Bacteroidetes, and Firmicutes were found in the ancient samples, whereas bacteria in the 8-year-old sample also included Cyanobacteria, Proteobacteria, and Deinococcus-Thermus. Isolates of the Gram-positive spore-forming bacterium Sporosarcina were found in 5 of 8 samples. The growth of these isolates at different temperatures was related to the phylogenetic distance among genotypes measured by BOX-PCR. These findings suggest that adaptation to growth at different temperatures had occurred among Sporosarcina genotypes in the Dry Valleys, causing the existence of physiologically distinct but closely related genotypes. Additionally, fully psychrophilic isolates (that grew at 15°C, but not 25°C) were found in ancient samples, but not in the modern sample. The preservation of viable bacteria in the Dry Valleys could potentially represent a legacy of bacteria that impacts on current microbial communities of this environment.

Antarctic lakes suggest millennial reorganizations of Southern Hemisphere atmospheric and oceanic circulation.

The phasing of millennial-scale oscillations in Antarctica relative to those elsewhere in the world is important for discriminating among models for abrupt climate change, particularly those involving the Southern Ocean. However, records of millennial-scale variability from Antarctica dating to the last glacial maximum are rare and rely heavily on data from widely spaced ice cores, some of which show little variability through that time. Here, we present new data from closed-basin lakes in the Dry Valleys region of East Antarctica that show high-magnitude, high-frequency oscillations in surface level during the late Pleistocene synchronous with climate fluctuations elsewhere in the Southern Hemisphere. These data suggest a coherent Southern Hemisphere pattern of climate change on millennial time scales, at least in the Pacific sector, and indicate that any hypothesis concerning the origin of these events must account for synchronous changes in both high and temperate latitudes.

Rapid response of a marine mammal species to holocene climate and habitat change.

Environmental change drives demographic and evolutionary processes that determine diversity within and among species. Tracking these processes during periods of change reveals mechanisms for the establishment of populations and provides predictive data on response to potential future impacts, including those caused by anthropogenic climate change. Here we show how a highly mobile marine species responded to the gain and loss of new breeding habitat. Southern elephant seal, Mirounga leonina, remains were found along the Victoria Land Coast (VLC) in the Ross Sea, Antarctica, 2,500 km from the nearest extant breeding site on Macquarie Island (MQ). This habitat was released after retreat of the grounded ice sheet in the Ross Sea Embayment 7,500-8,000 cal YBP, and is within the range of modern foraging excursions from the MQ colony. Using ancient mtDNA and coalescent models, we tracked the population dynamics of the now extinct VLC colony and the connectivity between this and extant breeding sites. We found a clear expansion signal in the VLC population approximately 8,000 YBP, followed by directional migration away from VLC and the loss of diversity at approximately 1,000 YBP, when sea ice is thought to have expanded. Our data suggest that VLC seals came initially from MQ and that some returned there once the VLC habitat was lost, approximately 7,000 years later. We track the founder-extinction dynamics of a population from inception to extinction in the context of Holocene climate change and present evidence that an unexpectedly diverse, differentiated breeding population was founded from a distant source population soon after habitat became available.

Transcatheter chemoembolization in the treatment of HCC in patients not eligible for curative treatments: midterm results of doxorubicin-loaded DC bead.

PURPOSE: To examine the results of segmental transcatheter arterial chemoembolization with doxorubicin-loaded DC Bead in the treatment of hepatocellular carcinoma (HCC) in non-surgical candidates. MATERIAL AND METHODS: Seventy-one patients (60% men; 11% women; mean age 63; range 46-71 years) with documented HCC of 3-10 cm in diameter (mean 6.2) were enrolled prospectively in the study. All patients had cirrhosis-related HCC that was developed on an underlying controlled hepatitis infection. Only patients with compensated cirrhosis--Child A or B--were included in this study. RESULTS: Overall complete response (CR) according to EASL on an intention to treat basis was seen in 11 patients who developed complete necrosis (15.5%). Objective response (OR) ranged from 66.2% to 85.5% across the four treatments. Survival at 12 months was 97.05%. Sustained CR was observed in 11 (16.1%), and OR in 49 (72%). Sustained partial response was seen in 49 patients (72.05%). Survival at 18 months was 94.1%. At 24 months follow-up survival was 91.1%. Sustained OR was seen in 45 patients (66.2%) while sustained CR was 16.1% (11/68). At 30 months survival was 88.2%. One patient with CR developed multifocal HCC in areas that most likely were not embolized during the previous embolization sessions. In this patient recurrence-free survival was 28 months. Alpha Fetroprotein levels decreased significantly in measurements 1 month post each procedure (p < 0.001). Bilirubin, gamma-GT, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase (ALP) showed only transient increases observed during the study period. Severe procedure-related complications were seen in 4.2% (cholecystitis: n = 1; liver abscess: n = 1; pleural effusion: n = 1). Post Embolization Syndrome (PES) was observed in all patients. CONCLUSION: Transcatheter arterial chemoembolization with DC Bead is an effective and safe procedure in the treatment of HCC patients not eligible for curative treatments with high rates of response and high rates of mid term survival.

Doxorubicin eluting beads-2: methods for evaluating drug elution and in-vitro:in-vivo correlation.

DC Bead is a sulfonate-modified, PVA-based microspherical embolisation agent approved for the treatment of hypervascular tumours and arterio-venous malformations. The beads have previously been shown to actively sequester oppositely charged drugs, such as doxorubicin hydrochloride (dox) by an ion-exchange mechanism. In order to characterise the release kinetics and predict the in vivo behaviour of drug eluting beads (DEB), two elution methods were utilised. The first, an application of the USP dissolution method Type II - Apparatus, enables study of the complete elution of loaded DC Bead in less than 4 h, allowing relatively rapid comparison to be made between different products and formulations. Release data obtained using this method were fitted to first order kinetics (R (2) > 0.998) and the elution constants shown to increase with the total surface area of the beads exposed to the elution medium. Diffusion coefficients were calculated adopting the Fickian diffusion model, which predicted slow elution rates under physiological conditions. The second method involved the use of a T-Apparatus where the drug experiences an element of diffusion through a static environment. This method was developed to resemble the in vivo situation in embolisation procedures more closely. Slow release of dox from DC Bead with half-lives over 1,500 h were predicted for all size ranges using a slow release model. A strong linear relationship was found between the release data from T-Apparatus and pharmacokinetic data obtained from patients treated with DC Bead loaded with dox in transarterial chemoembolisation (TACE) procedures. These data indicated a Level A in vitro-in vivo correlation (IVIVC) for the first 24 h post embolisation. Both systems developed were automated and good reproducibility was obtained for all samples, demonstrating the usefulness of these elution techniques for product development and comparative testing.

Transarterial chemoembolization of unresectable hepatocellular carcinoma with drug eluting beads: results of an open-label study of 62 patients.

The purpose of this study was to assess the safety and efficacy of doxorubicin-loaded beads (DC Beads) delivered by transarterial embolization for the treatment of unresectable hepatocellular carcinoma (HCC). This open-label, single-center, single-arm study included 62 cirrhotic patients with documented single unresectable HCC. Mean tumor diameter was 5.6 cm (range, 3-9 cm) classified as Okuda stages 1 (n = 53) and 2 (n = 9). Patients received repeat embolizations with doxorubicin-loaded beads every 3 months (maximum of three). The maximum doxorubicin dose was 150 mg per embolization, loaded in DC Beads of 100-300 or 300-500 microm. Regarding efficacy, overall, an objective response according to the European Association for the Study of the Liver criteria was observed in 59.6%, 81.8%, and 70.8% across three treatments. A complete response was observed in 4.8% after the first procedure and 3.6% and 8.3% after the second and third procedures, respectively. At 9 months a complete response was seen in 12.2%, an objective response in 80.7%, progressive disease in 6.8%, and 12.2% showed stable disease. Mean tumor necrosis ranged from 77.4% to 83.9% (range, 28.6%-100%) across three treatments. alpha-Fetoprotein levels showed a mean decrease of 1123 ng/ml (95% CI = 846-1399; p = 3 x 10(-11)) after the first session and remained stable after the second and third embolizations (42 and 70 ng/ml decrease, respectively). Regarding safety, bilirubin, gamma-glutamyl transferase, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase showed only transient increases during the study period. Severe procedure-related complications were seen in 3.2% (cholecystitis, n = 1; liver abscess, n = 1). Postembolization syndrome was observed in all patients. We conclude that hemoembolization using doxorubicin-loaded DC Beads is a safe and effective treatment of HCC as demonstrated by the low complication rate, increased tumor response, and sustained reduction of alpha-fetoprotein levels.

A strong constitutive ethylene-response phenotype conferred on Arabidopsis plants containing null mutations in the ethylene receptors ETR1 and ERS1.

BACKGROUND: The ethylene receptor family of Arabidopsis consists of five members, falling into two subfamilies. Subfamily 1 is composed of ETR1 and ERS1, and subfamily 2 is composed of ETR2, ERS2, and EIN4. Although mutations have been isolated in the genes encoding all five family members, the only previous insertion allele of ERS1 (ers1-2) is a partial loss-of-function mutation based on our analysis. The purpose of this study was to determine the extent of signaling mediated by subfamily-1 ethylene receptors through isolation and characterization of null mutations. RESULTS: We isolated new T-DNA insertion alleles of subfamily 1 members ERS1 and ETR1 (ers1-3 and etr1-9, respectively), both of which are null mutations based on molecular, biochemical, and genetic analyses. Single mutants show an ethylene response similar to wild type, although both mutants are slightly hypersensitive to ethylene. Double mutants of ers1-3 with etr1-9, as well as with the previously isolated etr1-7, display a constitutive ethylene-response phenotype more pronounced than that observed with any previously characterized combination of ethylene receptor mutations. Dark-grown etr1-9;ers1-3 and etr1-7;ers1-3 seedlings display a constitutive triple-response phenotype. Light-grown etr1-9;ers1-3 and etr1-7;ers1-3 plants are dwarfed, largely sterile, exhibit premature leaf senescence, and develop novel filamentous structures at the base of the flower. A reduced level of ethylene response was still uncovered in the double mutants, indicating that subfamily 2 receptors can independently contribute to signaling, with evidence suggesting that this is due to their interaction with the Raf-like kinase CTR1. CONCLUSION: Our results are consistent with the ethylene receptors acting as redundant negative regulators of ethylene signaling, but with subfamily 1 receptors playing the predominant role. Loss of a single member of subfamily 1 is largely compensated for by the activity of the other member, but loss of both subfamily members results in a strong constitutive ethylene-response phenotype. The role of subfamily 1 members is greater than previously suspected and analysis of the double mutant null for both ETR1 and ERS1 uncovers novel roles for the receptors not previously characterized.

Pharmacokinetic and safety study of doxorubicin-eluting beads in a porcine model of hepatic arterial embolization.

PURPOSE: To present the pathologic and pharmacokinetic findings from hepatic embolization in a porcine model comparing doxorubicin-eluting beads with bland embolization and to correlate these findings with in vitro release kinetics. MATERIALS AND METHODS: Drug-eluting beads (DEB; 100-300 microm and 700-900 microm) loaded with 37.5 mg doxorubicin per milliliter hydrated beads were used to embolize the hepatic artery feeding the left lobe of the liver in young adult Yucatan pigs (n = 5 per group). Control animals underwent embolization with bland beads (100-300 microm; n = 5). Systemic plasma levels of doxorubicin were measured and correlated to in vitro drug release. Blood sampling and histopathologic examination were performed during the 90-day follow-up. RESULTS: All animals underwent successful embolization, and the treatment was well tolerated. Mean volumes of beads administered were 2.0-3.4 mL, with mean doses of 127.5 mg and 78.7 mg of doxorubicin for the 100- to 300-microm and 700- to 900-microm DEB groups, respectively. Gross pathologic examination revealed no effects on organs other than the liver. There was a transient increase in liver enzyme levels, particularly in the groups of animals who underwent embolization with 100- to 300-microm DEB. Histopathologic study showed mostly nonnecrotic changes with bland beads, whereas the effects of DEB were more severe, with large areas of pannecrosis evident with the 100- to 300-microm DEB. Maximum plasma concentrations were 651 ng/mL and 42.8 ng/mL for the 100- to 300-microm and 700- to 900-microm DEB groups, respectively, observed at 1 minute for both groups. Correlation with in vitro data showed a strong linear relationship. CONCLUSIONS: Hepatic arterial embolization with DEB was shown to be safe and well tolerated. The locoregional delivery of doxorubicin from DEB caused targeted tissue damage with minimal systemic impact and could be a promising new approach to transarterial chemoembolization of solid tumors.

DC bead: in vitro characterization of a drug-delivery device for transarterial chemoembolization.

PURPOSE: The purpose of this investigation is to present the in vitro characterization and detailed drug-loading procedure for DC Bead, a microsphere product that can be loaded with chemotherapeutic agents for embolization. MATERIALS AND METHODS: DC Bead is an embolic microsphere product that is capable of being loaded with anthracycline drugs such as doxorubicin just before administration in a transarterial chemoembolization (TACE) procedure. Beads can be loaded from solutions prepared from doxorubicin powder or the doxorubicin HCl formulation. In this evaluation, bead sizes were measured by optical microscopy with video imaging. Gravimetric analysis demonstrated the effect of drug loading on bead water content, and its consequent impact on bead compressibility was determined. The subsequent deliverability of the beads was assessed by mixing the beads with contrast medium and saline solution and passing the beads through an appropriately sized microcatheter. A T-cell apparatus was used to monitor the in vitro elution of the drug from the beads over a period of 24 hours in various elution media. RESULTS: DC Bead spheres could be easily loaded with doxorubicin to a recommended level of 25 mg/mL of hydrated beads by immersion of the beads in the drug solution for 10-120 minutes depending on microsphere size. Other commercial embolic microspheres were shown not to load doxorubicin to the same extent or release it in the same fashion and were considered unsuitable for local drug delivery. Maximum theoretic capacity for DC Bead was approximately 45 mg/mL. Increase in doxorubicin loading resulted in a concomitant decrease in water content and consequential increase in bead resistance to compression force. Drug loading also resulted in a decrease in the average size of the beads, which was dependent on bead size and drug dose. This did not impact bead delivery at any drug loading level to a maximum of 37.5 mg/mL. Beads 100-700 microm in size could be delivered through 2.7-F microcatheters, whereas the 700-900-microm range required 3-F catheters. Modeling of the kinetics of drug elution from the beads in vitro at a loading dose of 25 mg/mL yielded calculated half-lives of 150 hours for the 100-300-microm range to a maximum of 1,730 hours for the 700-900-microm size range, which was dependent on the ionic strength of the elution medium. For comparison, there was a rapid loss of drug from an unstable Lipiodol emulsion with a half-life of approximately 1 hour. CONCLUSIONS: DC Bead can be loaded with doxorubicin to provide an accurate dosage of drug per unit volume of beads. Drug elution is dependent on ion exchange with the surrounding environment and is controlled and sustained, unlike the rapid separation of the drug from Lipiodol. Drug loading has no impact on the handling and deliverability of the beads, making them suitable for superselective TACE.