Effects of hepatic arterial yttrium-90 microsphere administration alone and combined with regional bromodeoxyuridine infusion in dogs

Brachytherapy by embolization with radiotherapeutic microspheres following intraarterial infusion of a radiosensitizer represents an attempt to combine several selective modalities into a more potent, focused attack on regionally confined tumors. In pursuit of this goal, we examined the ability of foxhounds with surgically implanted hepatic arterial (HA) delivery systems to tolerate a clinically relevant dosage of HA yttrium-90 (Y-90) by microsphere administration either alone or preceded by a 28-day constant HA infusion of either 5-bromo-2'-deoxyuridine (BUDR) or a control solution. Five dogs received BUDR (10 mg/kg/day) and five a control buffer infusion for 28 days immediately prior to the administration of Y-90-coated 15 micron resin microspheres (equivalent of 5000 rads to the entire liver) to each dog on day 31. In all animals, blood counts, bilirubin, amylase, appetite, weight, and behavior remained unchanged. Dogs receiving the microspheres after buffer infusion alone exhibited no hepatic enzyme alanine aminotransferase or alkaline phosphatase elevation. Alanine aminotransferase and alkaline phosphatase levels both rose during the third week of BUDR infusion, and while subsequent microsphere administration further increased enzyme levels, these levels had largely normalized by necropsy on day 82. At necropsy, the type and degree of hepatic toxicity among the animals receiving radioactive microspheres was comparable to that previously described in patients receiving external beam hepatic irradiation at conventional doses (2000-3000 rads). Also noted was a radiation-induced cholecystitis (due in large part to the gallbladder's total reliance on the hepatic artery for blood supply). One resin microsphere dog exhibited a small quantity of microspheres in the lungs causing focal radiation-induced granulomas suggesting the need to assess shunting of microspheres through the liver in clinical studies. Thus, HA Y-90 microspheres with BUDR can produce acceptable, nonlethal, and tolerable toxicities in this dog model suggesting that clinical studies of this combination are not likely to be contraindicated by synergistic toxicity. Although HA BUDR did not contribute significantly to the toxicity of the Y-90 microspheres, HA BUDR by itself administered uninterrupted for 4 weeks may, like HA FUDR (clinically), cause chemical hepatitis/cholangitis. The unexpected fragmentation of the resin spheres (albeit without myelosuppression) has led us to begin studies with a recently developed nondisruptible glass microsphere (ThereSphere) in which the Y-90 is part of the glass matrix and cannot leach.(ABSTRACT TRUNCATED AT 400 WORDS)     

Hepatic arterial perfusion scintigraphy with Tc-99m-MAA. Use of a totally implanted drug delivery system

Tc-99m-MAA hepatic arterial perfusion scintigraphy ( HAPS ) using a totally implanted drug delivery system was employed for hepatic arterial chemotherapy in 147 patients (335 studies). Complete perfusion of the involved liver was seen in 88% of patients initially [more so in those with normal hepatic vascular anatomy (93%) than those with vascular variants (79%)] and remained good on follow-up. In 67 consecutive patients (95 studies), arteriovenous shunting to the lung ranged from 0.4 to 32% (mean, 6.2% +/- 4.1 S.D.). Uptake at the tip of the catheter was increased in 20% of patients, but good perfusion was usually maintained. A significant decrease in hepatic and/or extrahepatic perfusion associated with a "hot spot" at the tip of the catheter indicated hepatic arterial thrombosis. Extrahepatic perfusion was seen in 14% of cases, usually in the distribution of the stomach, small bowel, and spleen. Significant symptoms of drug toxicity were seen in 70% of patients with extrahepatic perfusion, compared to 19% of those without it.     

A National Cost Analysis of Community Interventions to Prevent Underage Drinking and Prescription Drug Misuse

Prevention Science - This prospective cost analysis addresses a gap in the prevention literature by providing estimates of the typical real-world costs to implement community interventions focused...     

Exploring frontal asymmetry using functional near-infrared spectroscopy: a preliminary study of the effects of social anxiety during interaction and performance tasks

Preliminary studies examining brain function associated with social anxiety suggest the possibility of right-sided prefrontal activation associated with phobic stimulation. Although most existing neuroimaging techniques preclude participants from engaging in ecologically valid social tasks during assessment, functional near-infrared spectroscopy (fNIRS) is a promising new technique that permits such assessment. The present study investigated the utility of the fNIRS procedure and explored frontal asymmetry during in vivo social challenge tasks among female undergraduate students who scored in top and bottom percentiles on a social anxiety screening measure. Results revealed that participants in both groups experienced a significant increase in concentration of blood volume and oxygenated hemoglobin in the right hemisphere compared to the left hemisphere while giving a speech. Non-hemispheric effects were also observed. In addition, the high anxiety group showed a non-significant trend toward greater right frontal activity than the low anxiety group. This study highlights the utility of the fNIRS device in successfully assessing real-time changes in cerebrovascular response as a function of naturalistic social behavior, and supports the potential utility of this technology in the study of the neurophysiology of social anxiety.     

Development of visual and somatosensory attention of the reach-to-eat movement in human infants aged 6 to 12 months

The reach-to-eat movement is a natural act in which an object or food item is grasped and brought to the mouth. It is one of the earliest forelimb behaviours displayed by human infants, who bring almost all grasped objects to the mouth, and is used daily by adults. In adults, there is a tight coupling between visual attention and the advance phase of the reach-to-eat movement. The target is visually engaged just as hand advance is initiated and visually disengaged just as the target is grasped. This coupling of vision and hand advance suggests that advance is mediated by visual attention and withdrawal by somatosensation. The present study examined when the tight coupling between visual attention and the advance phase of the movement develops in infancy. In a longitudinal study, eight infants, aged 6–12 months, and 20 adults reached for familiar inanimate objects and food items. Visual gaze, hand movement and hand accuracy were measured using frame-by-frame video scoring and 2D kinematic analysis. The study found that the youngest infants (6–8 months) visually engaged the target well before initiating a reaching movement and continued to fixate on the target after it was grasped and as it was brought to the mouth. Between 10 and 12 months of age, infants began to visually engage the target just as the reaching movement was initiated and visually disengaged the target as it was grasped, as did the adults. Over the same developmental time period, the infants developed rotatory hand shaping movements, precision grasping, and improved targeting accuracy both for grasping the object and placing it into the mouth. The results suggest that visual guidance of advance and somatosensory guidance of withdrawal develop together and in concert with hand movement ability and skill.     

Age and distraction are determinants of performance on a novel visual search task in aged Beagle dogs

Aging has been shown to disrupt performance on tasks that require intact visual search and discrimination abilities in human studies. The goal of the present study was to determine if canines show age-related decline in their ability to perform a novel simultaneous visual search task. Three groups of canines were included: a young group (N = 10; 3 to 4.5 years), an old group (N = 10; 8 to 9.5 years), and a senior group (N = 8; 11 to 15.3 years). Subjects were first tested for their ability to learn a simple two-choice discrimination task, followed by the visual search task. Attentional demands in the task were manipulated by varying the number of distracter items; dogs received an equal number of trials with either zero, one, two, or three distracters. Performance on the two-choice discrimination task varied with age, with senior canines making significantly more errors than the young. Performance accuracy on the visual search task also varied with age; senior animals were significantly impaired compared to both the young and old, and old canines were intermediate in performance between young and senior. Accuracy decreased significantly with added distracters in all age groups. These results suggest that aging impairs the ability of canines to discriminate between task-relevant and -irrelevant stimuli. This is likely to be derived from impairments in cognitive domains such as visual memory and learning and selective attention.     

An update on new anticoagulants

A variety of new anticoagulants for the prevention and treatment of venous and arterial thromboembolism are under development. Designed to overcome the limitations of heparin and vitamin K antagonists, these new agents are at various stages of clinical testing. This paper reviews venous and arterial thrombogenesis, discusses the regulation of coagulation, identifies the molecular targets for new anticoagulants, describes new anticoagulants in more advanced stages of clinical testing, and provides perspective on how these agents will impact on practice.     

Similar hand shaping in reaching-for-food (skilled reaching) in rats and humans provides evidence of homology in release, collection, and manipulation movements

Many animal species use their forelimbs to assist in eating, such as occurs in a reach-to-eat task (skilled reaching) in which a forelimb is extended to grasp food that is placed in the mouth for eating. It is unclear the extent to which the skilled reaching movements of different species share common ancestry and so are homologous or evolved independently and so are analogous (homoplasy). Here hand shaping (the movements of the hand and digits) that occur as the hand is transported to the target, were examined using high-speed (1000 frames/s) video recording and kinematic measurement (Peak Motus) in the rat (Rattus norvegicus) and human (Homo sapiens). Ten movement similarities were identified from the point that the limb initiated transport towards the food item to the point that the food was grasped. The digits were closed and semi-flexed as the hand was lifted (released from a substrate) and supinated. They closed further as the hand was collected for aiming. They then extended as the hand was transported to the target and then opened in conjunction with pronation to orient the hand for grasping (manipulation). Finally the digits were flexed and closed for grasping. These movements occurred at approximately the same point of limb transport in both species even though the rat used a whole paw grasp and the humans used a pincer grasp. Bushbabies (Galago garnettii), titi monkeys (Callicebus brunneus), rhesus monkeys (Macaca mulatta) and the bonobo (Pan paniscus) displayed similar hand shaping in skilled reaching despite species differences in grasping movements. Homologous hand shaping in the rodent clade and the primate clade and within the primate lineage is discussed in relation to its possible derivation from hand shaping movements associated with stepping.