Investigating the health disparities in the association between lifestyle behaviors and the risk of head and neck cancer.

Many studies have reported a positive association between lower socioeconomic status (SES) and higher head and neck cancer (HNC) risk. Fewer studies have examined the impact of SES on the association between alcohol or cigarette use and HNC risk. The current case-control study (1104 HNC cases and 1363 controls) investigated the influence of education, a SES indicator, on the association between HNC and the use of alcohol, cigarettes, or betel quids in Taiwan, a country with universal health care. Our results showed a larger increase in HNC risk associated with alcohol among those with lower educational level (odds ratio [OR] = 2.07; 95% confidence interval [CI], 1.53-2.80) than those with higher educational level (OR = 1.38; 95% CI, 1.04-1.85) (heterogeneity-P = .03). Educational level had an influence on the association between alcohol use and HNC risk among those with genetic susceptibility (ALDH2-deficient) to the carcinogenic effect of alcohol. The association between cigarette or betel quid use and HNC risk was similar between the high and low educational groups. National policies and social interventions have led to the decline in the prevalence of cigarette and betel quid users in Taiwan. In contrast, due to the lack of adequate alcohol control policies, alcohol consumption in Taiwan has continued to rise. A higher impact of alcohol on HNC risk among lower SES individuals even with universal health care could be the result of insufficient alcohol control policies in Taiwan.

Economic and Environmental Considerations During Low Fresh Gas Flow Volatile Agent Administration After Change to a Nonreactive Carbon Dioxide Absorbent.

BACKGROUND: Reducing fresh gas flow (FGF) during general anesthesia reduces costs by decreasing the consumption of volatile anesthetics and attenuates their contribution to greenhouse gas pollution of the environment. The sevoflurane FGF recommendations in the Food and Drug Administration package insert relate to concern over potential toxicity from accumulation in the breathing circuit of compound A, a by-product of the reaction of the volatile agent with legacy carbon dioxide absorbents containing strong alkali such as sodium or potassium hydroxide. Newer, nonreactive absorbents do not produce compound A, making such restrictions moot. We evaluated 4 hypotheses for sevoflurane comparing intervals before and after converting from a legacy absorbent (soda lime) to a nonreactive absorbent (Litholyme): (1) intraoperative FGF would be reduced; (2) sevoflurane consumption per minute of volatile agent administration would be reduced; (3) cost savings due to reduced sevoflurane consumption would (modestly) exceed the incremental cost of the premium absorbent; and (4) residual wastage in discarded sevoflurane bottles would be <1%. METHODS: Inspired carbon dioxide (PICO2), expired carbon dioxide, oxygen, air, and nitrous oxide FGF, inspired volatile agent concentrations (FiAgent), and liquid volatile agent consumption were extracted from our anesthesia information management system for 8 4 week intervals before and after the absorbent conversion. Anesthesia providers were notified by e-mail and announcements at Grand Rounds about the impending change and were encouraged to reduce their average intraoperative sevoflurane FGF to 1.25 L/min. Personalized e-mail reports were sent every 4 weeks throughout the study period regarding the average intraoperative FGF (i.e., from surgery begin to surgery end) for each agent. Batch means methods were used to compare FGF, volatile agent consumption, net cost savings, and residual sevoflurane left in bottles to be discarded in the trash after filling vaporizers. The time from reaching a PICO2 = 3 mm Hg for 3 minutes until agent exhaustion (PICO2 = 5 mm Hg for 5 minutes) was evaluated. RESULTS: A total of N = 20,235 cases were analyzed (80.2% sevoflurane, 15.1% desflurane, and 4.7% isoflurane). Intraoperative FGF was reduced for cases in which sevoflurane was administered by 435 mL/min (95% confidence interval [CI], 391 to 479 mL/min; P < 10). Hypothesis 1 was accepted. Sevoflurane consumption per minute of administration decreased by 0.039 mL/min (95% CI, 0.029 to 0.049 mL/min; P < 10) after the change to the nonreactive absorbent. Hypothesis 2 was accepted. The difference in mean cost for the sum of the sevoflurane and absorbent purchases for each of the 10 4-week intervals before and after the absorbent switch was -$293 per 4-week interval (95% CI, -$2853 to $2266; P = 0.81). Hypothesis 3 was rejected. The average amount of residual sevoflurane per bottle was 0.67 ± 0.06 mL (95% CI, 0.54 to 0.81 mL per bottle; P < 10 vs 2.5 mL). Hypothesis 4 was accepted. Once the PICO2 reached 3 mm Hg for at least 3 consecutive minutes, the absorbent became exhausted within 95 minutes in most (i.e., >50%) canisters. CONCLUSIONS: We showed that an anesthesia department can transition to a premium, nonreactive carbon dioxide absorbent in a manner that is at least cost neutral by reducing FGF below the lower flow limits recommended in the sevoflurane package insert. This was achieved, in part, by electronically monitoring PICO2, automatically notifying the anesthesia technicians when to change the absorbent, and by providing personalized feedback via e-mail to the anesthesia providers.

Reduced medical costs and hospital days when using oral arsenic plus ATRA as the first-line treatment of acute promyelocytic leukemia.

We have demonstrated that oral arsenic (Realgar-Indigo naturalis formula, RIF) plus all-trans retinoic acid (ATRA) is not inferior to intravenous arsenic trioxide (ATO) plus ATRA as the first-line treatment of acute promyelocytic leukemia (APL). To compare the cost-effectiveness of oral and intravenous arsenic, we analyzed the results of 30 patients in each group involved in a randomized controlled trial at our center. The median total medical costs were $13,183.49 in the RIF group compared with $24136.98 in the ATO group (p<0.0001). This difference primarily resulted from the different costs of induction therapy (p=0.016) and maintenance treatment (p<0.0001). The length of hospitalization for the RIF group was significantly lower than that for the ATO group (24 vs. 31 days, p<0.0001) during induction therapy. During maintenance treatment, the estimated medical costs were $2047.14 for each patient in the RIF group treated at home compared with $11273.81 for each patient in the ATO group treated in an outpatient setting (p<0.0001). We conclude that oral RIF plus ATRA significantly reduced the medical costs and length of hospital stay during induction and remission therapy compared with ATO plus ATRA in APL patients.

Histologic Assessment of Quick-Set and Mineral Trioxide Aggregate Pulpotomies in a Canine Model.

INTRODUCTION: Quick-Set (Primus Consulting, Bradenton, FL) is a calcium aluminosilicate cement that is a potential alternative to mineral trioxide aggregate (MTA) with greater acid resistance and faster setting. The purpose of this study was to compare the effects of Quick-Set and MTA on pulpal tissues in response to pulpotomy procedures. METHODS: The pulp chambers of 42 maxillary teeth in 7 beagle dogs were accessed, and the coronal pulpal tissue was removed. Pulpotomy procedures were performed, placing the experimental materials directly over the radicular pulp tissues. The dogs were sacrificed at 70 days, and the teeth and surrounding tissues were removed and prepared for histologic analysis. The sections of the pulpotomy areas were scored for inflammation, pulp tissue organization, reactionary dentin formation, and quality of dentinogenesis. RESULTS: The Quick-Set group exhibited significantly more pulpal inflammation (P = .002) and significantly less pulp tissue organization (P = .004). No significant difference was noted for reactionary dentin formation (P = .526) and quality of dentinogenesis (P = .436). CONCLUSIONS: Compared with ProRoot White MTA (Dentsply Tulsa Dental Specialties, Tulsa, OK), Quick-Set exhibited more pulpal inflammation and decreased pulp tissue organization. No significant differences were noted for reactionary dentin formation and quality of dentinogenesis.

Economic evaluation of arsenic trioxide compared to all-trans retinoic acid + conventional chemotherapy for treatment of relapsed acute promyelocytic leukemia in Canada.

OBJECTIVES: Acute promyelocytic leukemia (APL) is an uncommon type of acute leukemia characterized by high early mortality. Current first-line treatments include all-trans retinoic acid (ATRA), anthracyclines, and other conventional chemotherapies (CTs). Although APL is generally associated with a good prognosis, about 20% of patients who achieve remission subsequently relapse and are resistant to the previously administrated treatment. The objective of this study was to assess, from a Canadian perspective, the economic impact of arsenic trioxide (ATO) compared to ATRA+CT for treatment of patients with relapsed/refractory APL. METHODS: The cost-effectiveness of ATO compared to ATRA+CT for treating patients with relapsed/refractory APL was assessed over a lifetime horizon using a Markov model. The model considers five health states: induction, second remission, treatment failure or relapse, postfailure, and death. Markov cycle length was 1 month for the first 24 months and 1 yr thereafter. The model also takes into account the incidence of grade 3-4 adverse events reported in clinical trials. Analyses were conducted from a Canadian Ministry of Health (MoH) and a societal perspective. RESULTS: Compared to ATRA+CT, ATO was associated with incremental cost-effectiveness ratios of $ 20,551/quality-adjusted life year (QALY) from a MoH perspective and $ 22,219/QALY from a societal perspective. Results of the probabilistic sensitivity analysis indicated that ATO is a cost-effective strategy in 99.27% and 98.98% of the simulations from a MoH and a societal perspective, respectively. CONCLUSIONS: This economic evaluation demonstrates that ATO is a cost-effective strategy compared to ATRA+CT for treatment of patients with relapsed/refractory APL in Canada.

Metrics, dose, and dose concept: the need for a proper dose concept in the risk assessment of nanoparticles.

In order to calculate the dose for nanoparticles (NP), (i) relevant information about the dose metrics and (ii) a proper dose concept are crucial. Since the appropriate metrics for NP toxicity are yet to be elaborated, a general dose calculation model for nanomaterials is not available. Here we propose how to develop a dose assessment model for NP in analogy to the radiation protection dose calculation, introducing the so-called "deposited and the equivalent dose". As a dose metric we propose the total deposited NP surface area (SA), which has been shown frequently to determine toxicological responses e.g. of lung tissue. The deposited NP dose is proportional to the total surface area of deposited NP per tissue mass, and takes into account primary and agglomerated NP. By using several weighting factors the equivalent dose additionally takes into account various physico-chemical properties of the NP which are influencing the biological responses. These weighting factors consider the specific surface area, the surface textures, the zeta-potential as a measure for surface charge, the particle morphology such as the shape and the length-to-diameter ratio (aspect ratio), the band gap energy levels of metal and metal oxide NP, and the particle dissolution rate. Furthermore, we discuss how these weighting factors influence the equivalent dose of the deposited NP.

Nanoscale radiotherapy with hafnium oxide nanoparticles.

AIM: There is considerable interest in approaches that could improve the therapeutic window of radiotherapy. In this study, hafnium oxide nanoparticles were designed that concentrate in tumor cells to achieve intracellular high-energy dose deposit. MATERIALS & METHODS: Conventional methods were used, implemented in different ways, to explore interactions of these high-atomic-number nanoparticles and ionizing radiation with biological systems. RESULTS: Using the Monte Carlo simulation, these nanoparticles, when exposed to high-energy photons, were shown to demonstrate an approximately ninefold radiation dose enhancement compared with water. Importantly, the nanoparticles show satisfactory dispersion and persistence within the tumor and they form clusters in the cytoplasm of cancer cells. Marked antitumor activity is demonstrated in human cancer models. Safety is similar in treated and control animals as demonstrated by a broad program of toxicology evaluation. CONCLUSION: These findings, supported by good tolerance, provide the basis for developing this new type of nanoparticle as a promising anticancer approach in human patients.

Assessment of the involvement of oxidative stress and Mitogen-Activated Protein Kinase signaling pathways in the cytotoxic effects of arsenic trioxide and its combination with sulindac or its metabolites: sulindac sulfide and sulindac sulfone on human leukemic cell lines.

The purpose of the study was to characterize the involvement of reactive oxygen species (ROS) in mediating the cytotoxic effects of arsenic trioxide (ATO) in combination with sulindac or its metabolites: sulfide (SS) and sulfone (SF) on human leukemic cell lines. Jurkat, HL-60, K562, and HPB-ALL cells were exposed to the drugs alone or in combinations. Cell viability was measured using WST-1 or XTT reduction tests and ROS production by dichlorodihydrofluorescein diacetate staining (flow cytometry). Modulation of (a) intracellular glutathione (GSH) level was done by using L: -buthionine sulfoximine (BSO) or diethylmaleate (DEM), (b) NADPH oxidase by using diphenyleneiodonium (DPI), and (c) MAP kinases by using SB202190 (p38), SP600125 (JNK), and U0126 (ERK) inhibitors. ATO cytotoxicity (0.5 or 1 µM) was enhanced by sulindacs, with higher activity showed by the metabolites. Strong cytotoxic effects appeared at SS and SF concentrations starting from 50 µM. The induction of ROS production seemed not to be the major mechanism responsible for the cytotoxicity of the combinations. A strong potentiating effect of BSO on ATO cytotoxicity was demonstrated; DEM (10-300 µM) and DPI (0.0025-0.1 µM; 72 h) did not influence the effects of ATO. Some significant decreases in the viability of the cells exposed to ATO in the presence of MAPK inhibitors comparing with the cells exposed to ATO alone were observed; however, the effects likely resulted from a simple additive cytotoxicity of the drugs. The combinations of ATO with sulindacs offer potential therapeutic usefulness.

Applicability of a "Pick a Winner" trial design to acute myeloid leukemia.

Randomized clinical trials remain the gold standard to establish efficacy and safety of new treatments. In acute myeloid leukemia, large trials have been associated with gradual improvement in outcome over 2 decades in younger patients without major differences emerging between treatments. By contrast, in older patients, improvement has been minimal, which justifies a new approach to identifying effective treatments. Given the urgent unmet need, and with the emergence of several novel agents or combinations that are likely to be expensive, large benefits are probably required to change clinical practice. To address this issue, we have evolved a "Pick a Winner" randomized progressive design with a rolling incorporation of novel treatments (drug X), which has been tested in older patients with acute myeloid leukemia. The rationale, operational characteristics, and initial experience of such an approach in the context of the United Kingdom National Cancer Research Institute AML16 trial are presented.

Cost-effectiveness of administering oral adsorbent AST-120 to patients with diabetes and advance-stage chronic kidney disease.

AIMS: AST-120, an oral adsorbent currently on-label only in Asian countries with phase III trials ongoing in the US, slows renal disease progression in patients with diabetes and advanced-stage chronic kidney disease (CKD). The objective of this study is to evaluate the cost-effectiveness of using AST-120 to treat patients with type 2 diabetes and advanced-stage CKD. METHODS: We used Markov model simulating the progression of diabetic nephropathy. Data were obtained from randomized trials estimating the progression of diabetic nephropathy with and without AST-120, and published literature. The base population was patients 60 years of age with type 2 diabetes and Stages 3 and 4 CKD. RESULTS: Treating patients with diabetes and advanced-stage CKD was found to be a dominant strategy, and quality of life improved further and more money was saved (0.22 quality-adjusted life years [QALYs] and $15,019 per patient) using AST-120 than the control strategy. Sensitivity analysis results were robust with regard to cost, adherence, and quality of life associated with AST-120 therapy, as well as age at diagnosis. The model was relatively sensitive to the effectiveness of AST-120. CONCLUSIONS: Treating patients with type 2 diabetes and advanced-stage CKD with AST-120 appears to extend life and reduce costs.

Cost-effectiveness of the oral adsorbent AST-120 versus placebo for chronic kidney disease.

AIM: This study was designed to evaluate the cost-effectiveness of AST-120, an oral adsorbent that attenuates the progression of chronic kidney disease. METHODS: We developed a Markov model with six health states, including four levels of serum creatinine, haemodialysis and death, using data from a randomized clinical trial conducted in Japan. Direct costs relevant to chronic kidney disease were calculated from a Japanese reimbursement perspective. Projected quality-adjusted life years (QALY) and costs were compared between the AST-120 and placebo groups. The target population was nondiabetic patients with serum creatinine levels from 5.0 to 8.0 mg/dL (442-707 micromol/L) at baseline. Probabilistic sensitivity analysis was performed to evaluate the stability of the results. RESULTS: At 3 years, mean total costs per patient were estimated at 6.67 million yen (US$56,982) in the AST-120 group and 9.38 million yen (US$80,196) in the placebo group. Mean total costs were 2.72 million yen (US$23,205) lower among patients receiving AST-120. QALY per patient were 0.295 (approximately 3.5 months) greater for patients receiving AST-120 than for those receiving placebo over 3 years. The finding that treatment with AST-120 dominated placebo (i.e. was less costly and resulted in more QALY) was upheld in sensitivity analyses. CONCLUSION: The use of AST-120 in patients with advanced chronic kidney disease may help to slow the rate of growth in expenditures for kidney disease.

Health economic evaluation of ferucarbotran-enhanced MRI in the diagnosis of liver metastases in colorectal cancer patients.

PURPOSE: The objective of our study was to analyze the health economic impact of ferucarbotran-enhanced magnetic resonance imaging (MRI) in the diagnosis of hepatic colorectal cancer metastases based on observed changes in medical management. MATERIALS AND METHODS: A decision tree simulating a patient's medical management was designed, comparing two scenarios: contrast-enhanced spiral computed tomography-based vs ferucarbotran-enhanced MRI-based (Resovist, Bayer Schering Pharma AG, Germany) diagnosis. A clinical trial in patients with presumed liver metastases (n=36) provided data on clinical decisions regarding the medical management options in relation to diagnostic outcomes: resection, chemotherapy, or best supportive care. A "gold standard" was established afterward, combining all the available clinical, imaging, laboratory, and pathology findings. A multidisciplinary panel formed by a hepatologist, a liver surgeon, and an interventional radiologist decided on the recommended medical management for each patient. Costs of medical resources associated with each management option (all expressed in Euro) were obtained from the public health insurance (average European values). Life expectancies for the different options were obtained from literature. RESULTS: Despite an initial extra cost of 338 Euro, a significant net saving of 1,443 Euro was obtained with ferucarbotran-enhanced MRI mainly because of avoiding unnecessary surgery. There was no significant difference in the predicted life expectancy between both arms, despite the large difference in medical decision. CONCLUSION: In this comparative medical decision analysis, it was shown that ferucarbotran-enhanced MRI has the potential to improve medical management and save health care costs.

Reduced incidence and severity of acute radiation mucositis by WF10 (IMMUNOKINE) as adjunct to standard of cure in the management of head & neck cancer patients.

OBJECTIVE: To evaluate the role of WF10-immunotherapy in reducing oro-pharyngeal complications in head and neck cancer chemoradiotherapy. MATERIAL AND METHOD: Thirteen patients were enrolled and assigned either to WF10- (n = 6) or control group (n = 7). After completion of their initial (neoadjuvant) chemotherapy, patients received WF10 intravenous infusions at 0.5 mL/kg body weight/day for five consecutive days and repeated every 3 weeks, concomitantly to standard radiotherapy (6,600-7,500 cGy, 200 cGy/day). Control patients received radiotherapy alone. RESULTS: Patients in the WF10-group had a lower incidence of oro-pharyngeal complications grade > 2, including oral mucositis (1 vs. 5), dysphagia (2 vs. 7), oral pain (3 vs. 5), taste alteration (4 vs. 6) and weight loss (2 vs. 4). The statistical significances were achieved for the parameters of oral mucositis (p = 0. 048) and dysphagia (p = 0.009). CONCLUSION: WF10 appears to reduce severity of oro-pharyngeal complications associated with standard chemoradiotherapy for head and neck cancer.

A novel method to radiolabel gastric retentive formulations for gamma scintigraphy assessment.

PURPOSE: To develop a robust radiolabeling technique to enable evaluation of difficult to radiolabel gastric retentive formulations using gamma scintigraphy. The use of a successful radiolabel will allow accurate assessment of the gastric residence time of the formulations. MATERIALS AND METHODS: The retention of two radionuclides, indium ((111)In) and samarium ((153)Sm), with and without further processing to improve radiolabel performance were evaluated in simulated gastric pH in vitro. The most successful formulation from the in vitro screening was further evaluated in preclinical and clinical studies. RESULTS: In vitro evaluation revealed significant radionuclide leakage at pH 1.5 for most radiolabeling attempts. Radionuclide leakage at pH 4.5 was less pronounced. The most successful radiolabel was formulated by adsorbing indium chloride onto activated charcoal, followed by entrapment in a cellulose acetate polymer melt. This provided the best radiolabel retention under both pH conditions in vitro. The radiolabel also proved to be successful during preclinical and clinical evaluations, allowing evaluation of gastric retention performance as well as complete gastrointestinal transit. CONCLUSION: A simple, yet robust radiolabel was developed for gastric retentive formulations to be evaluated pre-clinically or in a clinical setting by entrapping the radionuclide in an insoluble polymer through a simple polymer melt process.

Assessment of myocardial blood volume and water exchange: theoretical considerations and in vivo results.

The measured signal response in contrast-enhanced myocardial perfusion imaging has been shown to be affected by the rate of water exchange between the intravascular and extravascular compartments, the effect being particularly significant when intravascular contrast agents are used. In the present study, the T(1) relaxation rates were measured in eight pigs in blood and myocardium using a Look-Locker sequence after repeated injections of the intravascular contrast agent NC100150. The selection of myocardial region of interest was automated based on a minimum chi-square method. The intra- and extravascular water exchange rates and the myocardial blood volume were calculated from the measured relaxation rates by applying a two-compartment water exchange limited model that accounts for biexponential longitudinal relaxation. The following (mean +/- SD) values were obtained for the exchange frequency (f), the extravascular residence time (tau(e)), the intravascular residence time (tau(i)) and blood volume (BV), respectively: f = 1.39 +/- 0.52 s(-1), tau(e) = 708 +/- 264 ms, tau(i) = 107 +/- 63 ms, and BV = 11.2 +/- 2.1 mL/100 g. The mean value of f was found to be about 15% higher if biexponential relaxation was not accounted for, supporting the hypothesis that significant biexponential relaxation in tissues with large blood volume can lead to an overestimation of water exchange rates unless corrected for.

Reversibility of experimental acute renal failure in rats: assessment with USPIO-enhanced MR imaging.

The purpose of this study was to evaluate the potential reversibility of kidney lesions in an experimental model of acute renal failure using ultra-small particles of iron oxide (USPIO)-enhanced magnetic resonance (MR) imaging. This study was conducted in 21 uninephrectomized rats using a model of iodinated contrast media-induced renal failure. Thirteen rats received selective intraarterial renal administration of diatrizoate (370 mg/ml) and were compared with two control groups, including six animals injected with saline and two noninjected animals. MR imaging was performed 28 hours, 8 days, and 22 days after the procedure. Each MR session included axial and coronal T1- and coronal T2-weighted images before and after intravenous administration of 60 micromol Fe/kg of USPIO. The rats were sacrificed immediately after the last MR session for pathologic evaluation. MR images were qualitatively and quantitatively interpreted with respect to pathologic data, and differences were statistically studied. At day 22, histology showed 4 severely diseased kidneys with focal areas of necrosis, 5 mildly diseased kidneys with tubular vacuolization, and 12 normal kidneys. On quantitative data, a high correlation between the percentage of negative enhancement and histologic data was observed (P < 0.05). Qualitative interpretation showed a sensitivity and specificity of USPIO-enhanced T2-weighted MR images of 88% and 91%, respectively. Follow-up enhancement curves showed a constant increase of intrarenal USPIO negative enhancement in normal kidneys between day 1 and day 22, whereas all severely involved kidneys displayed higher USPIO negative enhancement at day 1 without significant changes over time until day 22. USPIO may be useful for in vivo follow-up of the reversibility of experimentally induced iodinated contrast media renal impairment in animals.

Assessment of peritoneal tolerance of a new MR blood pool contrast agent in rabbits.

OBJECTIVE: Fast 3D MR angiography in conjunction with a new blood pool contrast agent (iron oxide crystals) is a recently described method for detection and localization of intra-abdominal bleeding sites with high sensitivity and specificity. However, peritoneal reactions to the contrast agent have not yet been investigated. The purpose of this study was to assess the peritoneal tolerance of the contrast agent in an animal experiment. METHODS: Eleven rabbits were intraperitoneally injected with 5 mL diluted NC100150 Injection; two rabbits were used as the control group. Rabbits injected with NC100150 Injection were imaged in pairs at 12, 24, and 48 hours and 3 weeks, and a single rabbit was imaged at 72 hours and 1 and 2 weeks after the intraperitoneal administration of the agent. Immediately after imaging, the rabbits were killed and an autopsy was performed. Samples of peritoneal surfaces and intra-abdominal organs were harvested for histology. MR imaging, gross pathology, and histology were evaluated. RESULTS: MR imaging and gross pathology demonstrated the presence of intraperitoneal contrast agent up to 24 hours after administration. Histology revealed a considerable amount of iron in the peritoneum, mesenteric fat, and lymph nodes within the first 24 hours. In most cases, iron was rapidly cleared from these sites within 2 days; in one animal, however, iron was detectable up to 1 week. No signs of inflammation or fibrosis were detected. CONCLUSIONS: This study shows no evidence of inflammatory reactions or signs of fibrosis after the intraperitoneal application of NC100150 Injection.

NC100100, a new echo contrast agent for the assessment of myocardial perfusion--safety and comparison with technetium-99m sestamibi single-photon emission computed tomography in a randomized multicenter study.

BACKGROUND AND HYPOTHESIS: Myocardial contrast echocardiography using second-generation agents has been proposed to study myocardial perfusion. A placebo-controlled, multicenter trial was conducted to evaluate the safety, optimal dose, and imaging mode for NC100100, a novel intravenous second-generation echo contrast agent, and to compare this technique with technetium-99m sestamibi (MIBI) single-photon emission computed tomography (SPECT). METHODS: In a placebo-controlled, multicenter trial, 203 patients with myocardial infarction > 5 days and < 1 year previously underwent rest SPECT and MCE. Fundamental and harmonic imaging modes combined with continuous and electrocardiogram-- (ECG) triggered intermittent imaging were used. Six dose groups (0.030, 0.100, and 0.300 microliter particles/kg body weight for fundamental imaging; and 0.006, 0.030, and 0.150 microliter particles/kg body weight for harmonic imaging) were tested. A saline group was also included. Safety was followed for 72 h after contrast injection. Myocardial perfusion by MCE was compared with myocardial rest perfusion imaging using MIBI as a tracer. RESULTS: NC100100 was well tolerated. No serious adverse events or deaths occurred. No clinically relevant changes in vital signs, laboratory parameters, and ECG recordings were noted. There was no significant difference between adverse events in the NC100100 (25.7%) and in the placebo group (17.9%, p = 0.3). Intermittent harmonic imaging using the intermediate dose was superior to all other modalities, allowing the assessment of perfusion in 76% of all segments. Eighty segments (96%) with normal perfusion by SPECT imaging also showed myocardial perfusion with MCE. However, a substantial percentage of segments (61-80%) with perfusion defects by SPECT imaging also showed opacification by MCE. This resulted in an overall agreement of 66-81% and a high specificity (80-96%), but in low sensitivity (20-39%) of MCE for the detection of perfusion defects. CONCLUSION: NC100100 is safe in patients with myocardial infarction. Intermittent harmonic imaging with a dose of 0.03 microliter particles/kg body weight can be proposed as the best imaging protocol. Myocardial contrast echocardiography with NC 100100 provides perfusion information in approximately 76% of segments and results in myocardial opacification in the vast majority of segments with normal perfusion as assessed by SPECT. Although the discrepancies between MCE and SPECT with regard to the definition of perfusion defects requires further investigation, MCE with NC 100100 is a promising technique for the noninvasive assessment of myocardial perfusion.

[A comparison between GE and SE sequences in MRT after the i.v. application of superparamagnetic iron particles in the assessment of experimentally induced soft-tissue osteosarcomas]. / Vergleich zwischen GE- und SE-Sequenzen in der MRT nach i.v. Applikation von superparamagnetischen Eisenpartikeln bei der Beurteilung von experimentell induzierten Osteosarkomen der Weichteile.

PURPOSE: An MRI study on experimentally induced osteosarcomas of the peripheral soft-tissues in nude rats was conducted, comparing SE and GE sequences after i.v. application of superparamagnetic iron oxides with regard to contrast and image quality. MATERIAL AND METHODS: 40 nude rats with an osteosarcoma in the right hind leg and 7 tumour-free animals were measured without, one and 48 hours after i.v.-injection of the contrast medium. 4 SE and 3 GE sequences with different parameters and slice orientation were applied. The contrast medium consisted of Fe3O4 particles with a core diameter of 6-8 nm and a coating material of polyethylene glycol (PEG). The laboratory animals were divided into 5 groups of 7-12 animals each. The rats of the first 4 groups were given a contrast-medium dosage of 100, 150, 200 and 250 mumol Fe/kg body weight, respectively. The animals of the fifth group were tumour-free and served as controls. RESULTS: The minimum dosage for detection of Fe3O4-containing PEG magnetites, one hour after application, was established at 100-150 mumol Fe/kg body weight. The higher the dosage of the contrast medium, the more signal alterations could be measured. The GE sequences were more sensitive than SE sequences. One GE sequence with the parameters TR 90 ms, TE 13 ms, FL 8 degrees turned out to be highly sensitive. CONCLUSION: Superparamagnetic iron oxides induce signal alterations in tumours of the peripheral soft tissue. GE sequences proved to be more sensitive than SE sequences.