RESUMEN

Echocardiographic evaluation for the recognition of intravascular and left atrial appendage thrombus remains a difficult problem. A thrombus-specific ultrasonographic contrast agent has the potential for an alternative approach for their delineation. The aim of this study was to investigate the usefulness of thrombus-specific contrast agent MRX-408A1 for the detection of acute experimentally created intravascular and intracardiac thrombus. In the first study, we created inferior vena cava thrombus in 9 dogs. With the use of fundamental 2-dimensional echocardiography imaging, we recorded images of the inferior vena cava thrombus at baseline (n = 9), with the thrombus-specific contrast agent MRX-408A1 (n = 9), and with nonspecific contrast agent MRX-113 (n = 6). In the second study, we created a left atrial appendage thrombus in 8 dogs. We imaged left atrial appendage thrombus at baseline and during MRX-113 and MRX-408A1 infusion. Thrombus was successfully created in all dogs in study 1 and in 6 of 8 dogs in study 2. MRX-408A1 produced a visually apparent increase in ultrasonographic contrast enhancement of the thrombus in all cases in which thrombus was found on autopsy. In both studies, MRX-408A1 increased the videointensity of the thrombus significantly compared with baseline images and images obtained during MRX-113 infusion. The size of the visually detectable thrombus on the image was also significantly larger during MRX-408A1 infusion than at baseline and during MRX-113 infusion. These data provide in vivo demonstration of the efficacy of a thrombus-specific contrast agent, MRX-408A1, in the detection of acute intravascular and intracardiac thrombus. It has the potential to improve the diagnostic accuracy of ultrasonography for the detection of acute thrombi at various cardiovascular sites in the clinical setting.

Asunto(s)

RESUMEN

RATIONALE AND OBJECTIVES: A thrombus-specific ultrasound contrast agent, MRX-408, has been developed recently. This agent consists of phospholipid-coated microbubbles with a ligand capable of targeting the GPIIb/IIIa receptor, thereby allowing the microbubbles to bind with thrombi rich in activated platelets. In vitro and in vivo animal experiments have been conducted to examine imaging enhancement and sonothrombolysis using this agent compared with a nontargeted agent. METHODS: For clot binding, blood-smeared slides were incubated with microbubbles and examined under a light microscope. Change in backscatter signals from the blood clots after binding was examined by both an ultrasound scanner and two single-element transducers arranged in a transmitter-receiver pair. For clot lysis, either 1-MHz or 20-KHz ultrasound was used to enhance the lysing effects of MRX-408 with or without urokinase. RESULTS: Evidence of binding was demonstrated under a microscope. In vitro experiments showed that the "acoustic signature", or properties, of blood clots changed after binding. Clots became more echogenic and nonlinear. In vivo fundamental ultrasound imaging confirmed that as a result of binding, blood clots were more visible, the area of detection was improved, and shadowing behind clots was more noticeable. Under 1-MHz ultrasound and 30 minutes of treatment, lysis efficiency reached 34% with MRX-408, whereas there was no visible clot lysis with saline. CONCLUSION: The results of these preliminary studies show that as a contrast agent, MRX-408 enhanced clots under ultrasound imaging and facilitated sonothrombolysis with or without thrombolytic drugs.

Asunto(s)

RESUMEN

RATIONALE AND OBJECTIVES: Paclitaxel-carrying lipospheres (MRX-552) were developed and evaluated as a new ultrasound contrast agent for chemotherapeutic drug delivery. METHODS: Paclitaxel was suspended in soybean oil and added to an aqueous suspension of phospholipids in vials. The headspace of the vials was replaced with perfluorobutane gas; the vials were sealed, and they were agitated at 4200 rpm on a shaking device. The resulting lipospheres containing paclitaxel were studied for concentration, size, acute toxicity in mice, and acoustic activity and drug release with ultrasound. Lipospheres containing sudan black dye were produced to demonstrate the acoustically active liposphere (AAL)-ultrasound release concept. RESULTS: Acoustically active lipospheres containing paclitaxel had a mean particle count of approximately 1 x 10(9) particles per mL and a mean size of 2.9 microns. Acute toxicity studies in mice showed a 10-fold reduction in toxicity for paclitaxel in AALs compared with free paclitaxel. The AALs reflected ultrasound as a contrast agent. Increasing amounts of ultrasound energy selectively ruptured the AALs and released the paclitaxel. CONCLUSIONS: Acoustically active lipospheres represent a new class of acoustically active drug delivery vehicles. Future studies will assess efficacy of AALs for ultrasound-mediated drug delivery.

Asunto(s)

RESUMEN

Ultrasound is used as a primary diagnostic technique for the detection of deep venous thrombosis. The purpose of this study is to describe the development of a new thrombus-specific ultrasound contrast agent: The linear hexapeptide (lysine-glutamine-alanine-glycine-aspartate-valine) was synthesized and coupled to a lipid moiety. The targeted lipid was then incorporated into the lipid blend for the contrast agent Aerosomes (ImaRx, Tucson, AZ, USA). The lipid blend was used to entrap perfluorobutane microbubbles. The microbubbles were sized and studied in vitro for acoustic stability, binding to blood clot, and ultrasound enhancement in vitro of blood clot. The results showed the mean size of the specific ultrasound contrast agent (MRX-408) was about 2.0 microm. The microbubbles appeared as smooth spherical structures. Microscopy showed that the targeted bubbles bound to blood clot whereas control, nontargeted bubbles did not bind to blood clot. In vitro acoustic study showed similar stability of the microbubbles compared with control microbubbles. The targeted microbubbles enhanced blood clot in vitro whereas nontargeted microbubbles did not enhance clot. Thus this promising new thrombus-specific ultrasound contrast agent could potentially improve detection of thrombosis by ultrasound and might be useful for distinguishing between new and old thrombosis. In vivo studies are in progress.

Asunto(s)

Asunto(s)

RESUMEN

RATIONALE AND OBJECTIVES: Cationic liposomes are under development as delivery agents for gene therapy. The authors studied the effect of ultrasound on gene expression in cell cultures during liposomal transfection experiments. METHODS: Cationic liposomes of dipalmitoylethylphosphocholine and dioleoylphosphatidylethanolamine were used to transfect cultured HeLa, NIH/3T3, and C127I cells with the chloramphenicol acetyl transferase (CAT) gene. A cell viability assay was performed on cultured HeLa cells that were exposed to varying durations (5 seconds or 30 seconds) and intensities of 1 MHz continuous-wave therapeutic ultrasound after transfection, and gene expression was measured 48 hours later. RESULTS: Cells survived 30 seconds or less at a power level of 0.5 watts/cm2 but died when exposed for 60 seconds or longer. Exposures of 5 seconds and 30 seconds of ultrasound resulted in significant increases in gene expression in all three cell types tested in this experiment. CONCLUSIONS: Relatively low levels of ultrasound energy can be used to enhance gene expression from liposomal transfection. Additional experiments are needed to optimize this process and clarify the mechanisms involved.

Asunto(s)

RESUMEN

Populations of feral pigs (Sus scrofa) may serve as an environmental reservoir of Cryptosporidium parvum oocysts and Giardia sp. cysts for source water. We conducted a cross-sectional study to determine the prevalence of and associated demographic and environmental risk factors for the shedding of C. parvum oocysts and Giardia sp. cysts. Feral pigs were either live-trapped or dispatched from 10 populations located along the coastal mountains of western California, and fecal samples were obtained for immunofluorescence detection of C. parvum oocysts and Giardia sp. cysts. We found that 12 (5.4%) and 17 (7.6%) of 221 feral pigs were shedding C. parvum oocysts and Giardia sp. cysts, respectively. The pig's sex and body condition and the presence of cattle were not associated with the probability of the shedding of C. parvum oocysts. However, younger pigs (< or = 8 months) and pigs from high-density populations (> 2.0 feral pigs/km2) were significantly more likely to shed oocysts compared to older pigs (> 8 months) and pigs from low-density populations (< or = 1.9 feral pigs/km2). In contrast, none of these demographic and environmental variables were associated with the probability of the shedding of Giardia sp. cysts among feral pigs. These results suggest that given the propensity for feral pigs to focus their activity in riparian areas, feral pigs may serve as a source of protozoal contamination for surface water.

Asunto(s)

RESUMEN

To answer the question as to the prevalence of sensori-neural hearing loss (SNHL) among neonates receiving ECMO, a retrospective chart review was conducted on 198 infants having surgery between November 1987 and January 1995. One hundred fifty-seven (79.7%) survived. One hundred thirty infants met our criteria of having a pre-discharge auditory brainstem evoked response (ABR) test and at least one follow-up behavioral audiologic examination. Strict criteria were set for normal hearing on both the ABR and follow-up examinations. Only follow-up results are reported. At the time of the most recent follow-up examination, two children could not be adequately studied, 106 exhibited normal hearing, 21 (16%) exhibited either unilateral or bilateral conductive hearing loss and three (2.3%) exhibited unilateral or bilateral SNHL. Only one child is using amplification. With the largest sample size to date, we found a lower prevalence of SNHL after ECMO than has been previously noted in the literature. Although the prevalence of hearing loss is low, the post-ECMO group of infants must be considered at risk for hearing loss. The prevalence of hearing loss cannot be based solely on a pre-discharge ABR, i.e. ongoing follow-up testing is necessary.

Asunto(s)

RESUMEN

We used a combination of Telazol (3.3 mg/kg) and xylazine hydrochloride (1.6 mg/kg to immobilize 144 wild pigs (Sus scrofa) with blow darts. This drug combination was safe and effective for rapidly immobilizing animals ranging in size from 34 to > 170 kg and avoided difficulties associated with hand injections. For 123 single injection immobilizations, mean (+/- SD) induction times and effective handling periods averaged 5 (+/- 2.5) and 52 (+/- 18) min, respectively, and animals generally recovered for release within 120 min of initial injections. Animals that required two injections to immobilize (n = 21) received lower initial doses of Telazol and xylazine hydrochloride than those immobilized with a single injection because of errors in estimating body sizes; we found that there was a threshold dose required to immobilize wild pigs from 2.8 to 3.3 mg/kg Telazol and 1.4 to 1.6 mg/kg xylazine. Although neither age or sex influenced immobilization parameters, animals in good condition required longer to recover than those in poor condition. However, animals immobilized with two injections recovered as rapidly as those immobilized with a single injection. Heart rates and body temperatures declined slightly during the immobilization period, but respiration rates and blood oxygen saturation levels remained stable. In general, single injection immobilizations were preferable because they minimized problems associated with injecting partially immobilized animals. because it was difficult to accurately estimate the sizes of large wild pigs (> or = 90 kg), and because wild pigs that were partially immobilized were difficult to handle, we recommend increasing the drug doses to 4 mg/kg Telazol and 2 mg/kg xylazine hydrochloride when injecting relatively large animals to assure single injection immobilizations. Although recovery periods may be prolonged, higher doses of Telazol and xylazine should be safe based on data from domestic pigs.

Asunto(s)

RESUMEN

A 12 month retrospective study was conducted on 54 children discharged from the Children's Hospital, Birmingham, Alabama, with a diagnosis of generalized meningitis, a major cause of post-natal sensorineural hearing loss (SNHL). Of these high risk patients, 38 or 70% had Haemophilus influenza meningitis and fully 40% of those children tested audiometrically were determined to have SNHL. Because there would appear to be an increase in SNHL in the post meningeal population, all children with a diagnosis of Haemophilus influenza, pneumococcal, or meningococcal meningitis should have an audiological workup, preferably prior to discharge from the hospital.

Asunto(s)

Asunto(s)

Asunto(s)

Asunto(s)