Patient dose management in fluoroscopy : the use of DRL : P123

Purpose: To set local dose reference levels (DRL) that allow radiologists to control stochastic and deterministic effects. Methods and materials: Dose indicators for cerebral angiographies and hepatic embolizations were collected during 4 months and analyzed in our hospital. The data were compared when an image amplifier was used instead of a flat panel detector. The Mann and Whitney test was used. Results: For the 40 cerebral angiographies performed the DRL for DAP, fluoroscopy time and number of images were respectively: 166 Gy.cm2, 19 min, 600. The maximum DAP was 490 Gy.cm2 (fluoroscopy time: 84 min). No significant difference for fluoroscopy time and DAP for image amplifier and flat panel detector (p = 0.88) was observed. The number of images was larger for flat panel detector (p = 0.004). The values obtained were slightly over the present proposed DRL: 150 Gy.cm2, 15 min, 400. Concerning the 13 hepatic embolizations the DRL for DAP fluoroscopy time and number of images were: 315 Gy.cm2, 25 min, 370. The maximum DAP delivered was 845 Gy.cm2 (fluoroscopy time of 48 min). No significant difference between image amplifier and flat panel detector was observed (p = 0.005). The values obtained were also slightly over the present proposed DRL: 300 Gy.cm2, 20 min, 200. Conclusion: These results show that the introduction of flat panel detector did not lead to an increase in patient dose. A DRL concerning the cumulative dose (that allow to control the deterministic effect) should be introduced to allow radiologists to have full control on the risks associated with ionizing radiations. Results of this on going study will be presented.

Low dose endoluminal photodynamic therapy improves murine T cell-mediated colitis.

BACKGROUND AND STUDY AIMS: Low dose photodynamic therapy (LDPDT) may modify the mucosal immune response and may thus provide a therapy for Crohn's disease. We evaluated the efficacy and safety of this technique in a murine T cell-mediated colitis model. METHODS: The safety of LDPDT was first tested in BALB/c mice. Naïve T cells were used to induce colitis in mice with severe combined immunodeficiency, which were followed up endoscopically, and a murine endoscopic index of colitis (MEIC) was developed. The efficacy of LDPDT (10 J/cm (2); delta-aminolevulinic acid, 15 mg/kg bodyweight) was then tested on mice with moderate colitis, while a disease control group received no treatment. The MEIC, weight, length, and histology of the colon, cytokine expression indices, number of mucosal CD4 (+) T cells, percentage of apoptotic CD4 (+) T cells, body weight, and systemic side effects were evaluated. RESULTS: LDPDT improved the MEIC ( P = 0.011) and the histological score ( P = 0.025), diminished the expression indices of the proinflammatory cytokines, interleukin-6 ( P = 0.042), interleukin-17 ( P = 0.029), and interferon-gamma ( P = 0.014), decreased the number of mucosal CD4 (+) T cells, and increased the percentage of apoptotic CD4 (+) T cells compared with the disease control group. No local or systemic side effects occurred. CONCLUSION: LDPDT improves murine T cell-mediated colitis, decreases the proinflammatory cytokines interleukin-6, interleukin-17, and interferon-gamma, and decreases the number of CD4 (+) T cells. No adverse events were observed. Therefore, this technique is now being evaluated in patients with inflammatory bowel disease.

A threefold dose intensity treatment with ifosfamide, carboplatin, and etoposide for patients with small cell lung cancer: a randomized trial.

BACKGROUND: The dose intensity of chemotherapy can be increased to the highest possible level by early administration of multiple and sequential high-dose cycles supported by transfusion with peripheral blood progenitor cells (PBPCs). A randomized trial was performed to test the impact of such dose intensification on the long-term survival of patients with small cell lung cancer (SCLC). METHODS: Patients who had limited or extensive SCLC with no more than two metastatic sites were randomly assigned to high-dose (High, n = 69) or standard-dose (Std, n = 71) chemotherapy with ifosfamide, carboplatin, and etoposide (ICE). High-ICE cycles were supported by transfusion with PBPCs that were collected after two cycles of treatment with epidoxorubicin at 150 mg/m(2), paclitaxel at 175 mg/m(2), and filgrastim. The primary outcome was 3-year survival. Comparisons between response rates and toxic effects within subgroups (limited or extensive disease, liver metastases or no liver metastases, Eastern Cooperative Oncology Group performance status of 0 or 1, normal or abnormal lactate dehydrogenase levels) were also performed. RESULTS: Median relative dose intensity in the High-ICE arm was 293% (range = 174%-392%) of that in the Std-ICE arm. The 3-year survival rates were 18% (95% confidence interval [CI] = 10% to 29%) and 19% (95% CI = 11% to 30%) in the High-ICE and Std-ICE arms, respectively. No differences were observed between the High-ICE and Std-ICE arms in overall response (n = 54 [78%, 95% CI = 67% to 87%] and n = 48 [68%, 95% CI = 55% to 78%], respectively) or complete response (n = 27 [39%, 95% CI = 28% to 52%] and n = 24 [34%, 95% CI = 23% to 46%], respectively). Subgroup analyses showed no benefit for any outcome from High-ICE treatment. Hematologic toxicity was substantial in the Std-ICE arm (grade > or = 3 neutropenia, n = 49 [70%]; anemia, n = 17 [25%]; thrombopenia, n = 17 [25%]), and three patients (4%) died from toxicity. High-ICE treatment was predictably associated with severe myelosuppression, and five patients (8%) died from toxicity. CONCLUSIONS: The long-term outcome of SCLC was not improved by raising the dose intensity of ICE chemotherapy by threefold.

Renal failure after high-dose methotrexate in a child homozygous for MTHFR C677T polymorphism

We report the case of an 11-year-old female treated for mediastinal T-cell lymphoma who presented renal failure following the second cycle of high-dose methotrexate (HDMTX). Because of life threatening plasma methotrexate (MTX) levels, carboxypeptidase G2 (CPDG2) was administered resulting in a dramatic decrease within 1 hr. The patient recovered from renal failure and no other side effects were observed. Homozygosity for the methylentetrahydrofolate reductase (MTHFR) C677T polymorphism diagnosed by molecular genetic analysis was the only explanation for this toxicity.

Dowel Bar Optimization: Phases I and II, October 2001

America’s roadways are in serious need of repair. According to the American Society of Civil Engineers (ASCE), one-third of the nation’s roads are in poor or mediocre condition. ASCE has estimated that under these circumstances American drivers will sacrifice $5.8 billion and as many as 13,800 fatalities a year from 1999 to 2001 ( 1). A large factor in the deterioration of these roads is a result of how well the steel reinforcement transfers loads across the concrete slabs. Fabricating this reinforcement using a shape conducive to transferring these loads will help to aid in minimizing roadway damage. Load transfer within a series of concrete slabs takes place across the joints. For a typical concrete paved road, these joints are approximately 1/8-inch gaps between two adjacent slabs. Dowel bars are located at these joints and used to transfer load from one slab to its adjacent slabs. As long as the dowel bar is completely surrounded by concrete no problems will occur. However, when the hole starts to oblong a void space is created and difficulties can arise. This void space is formed due to a stress concentration where the dowel contacts the concrete. Over time, the repeated process of traffic traveling over the joint crushes the concrete surrounding the dowel bar and causes a void in the concrete. This void inhibits the dowel’s ability to effectively transfer load across the joint. Furthermore, this void gives water and other particles a place to collect that will eventually corrode and potentially bind or lock the joint so that no thermal expansion is allowed. Once there is no longer load transferred across the joint, the load is transferred to the foundation and differential settlement of the adjacent slabs will occur.

Status of eye lens radiation dose monitoring in European hospitals.

A questionnaire was developed by the members of WG12 of EURADOS in order to establish an overview of the current status of eye lens radiation dose monitoring in hospitals. The questionnaire was sent to medical physicists and radiation protection officers in hospitals across Europe. Specific topics were addressed in the questionnaire such as: knowledge of the proposed eye lens dose limit; monitoring and dosimetry issues; training and radiation protection measures. The results of the survey highlighted that the new eye lens dose limit can be exceeded in interventional radiology procedures and that eye lens protection is crucial. Personnel should be properly trained in how to use protective equipment in order to keep eye lens doses as low as reasonably achievable. Finally, the results also highlighted the need to improve the design of eye dosemeters in order to ensure satisfactory use by workers.

Randomized controlled trial of olanzapine or chlorpromazine as addition to lithium in the treatment of a first manic episode with psychotic features: an 8-week, flexible dose, single-blind trial

Background: Association of mood stabiliser and antipsychotic medication is indicated in psychotic mania, but specific guidelines for the treatment of a first episode of psychotic mania are needed. Aims: To compare safety and efficacy profiles of chlorpromazine and olanzapine augmentation of lithium treatment in a first episode of psychotic mania. Methods: A total of 83 patients were randomised to either lithium + chlorpromazine or lithium + olanzapine in an 8-week trial. Data was collected on side effects, vital signs and weight modifications, as well as on clinical variables. Results: There were no differences in the safety profiles of both medications, but patients in the olanzapine group were significantly more likely to have reached mania remission criteria after 8 weeks. Mixed effects models repeated measures analysis of variance showed that patients in the olanzapine group reached mania remission significantly earlier than those in the chlorpromazine group. Conclusions: These results suggest that while olanzapine and chlorpromazine have a similar safety profile in a cohort of patients with first episode of psychotic mania, the former has a greater efficacy on manic symptoms. On this basis, it may be a better choice for such conditions.

Dowel Bar Optimization: Phases I and II, October 2001

America’s roadways are in serious need of repair. According to the American Society of Civil Engineers (ASCE), one-third of the nation’s roads are in poor or mediocre condition (1). ASCE has estimated that under these circumstances American drivers will sacrifice $5.8 billion and as many as 13,800 fatalities a year from 1999 to 2001 ( 1). A large factor in the deterioration of these roads is a result of how well the steel reinforcement transfers loads across the concrete slabs. Fabricating this reinforcement using a shape conducive to transferring these loads will help to aid in minimizing roadway damage. Load transfer within a series of concrete slabs takes place across the joints. For a typical concrete paved road, these joints are approximately 1/8-inch gaps between two adjacent slabs. Dowel bars are located at these joints and used to transfer load from one slab to its adjacent slabs. As long as the dowel bar is completely surrounded by concrete no problems will occur. However, when the hole starts to oblong a void space is created and difficulties can arise. This void space is formed due to a stress concentration where the dowel contacts the concrete. Over time, the repeated process of traffic traveling over the joint crushes the concrete surrounding the dowel bar and causes a void in the concrete. This void inhibits the dowel’s ability to effectively transfer load across the joint. Furthermore, this void gives water and other particles a place to collect that will eventually corrode and potentially bind or lock the joint so that no thermal expansion is allowed. Once there is no longer load transferred across the joint, the load is transferred to the foundation and differential settlement of the adjacent slabs will occur.

Material and Construction Optimization for Prevention of Premature Pavement Distress in PCC Pavements, September 2004

The chemistry of today’s concrete mixture designs is complicated by many variables, including multiple sources of aggregate and cements and a plethora of sometimes incompatible mineral and chemical admixtures. Concrete paving has undergone significant changes in recent years as new materials have been introduced into concrete mixtures. Supplementary cementitious materials such as fly ash and ground granulated blast furnace slag are now regularly used. In addition, many new admixtures that were not even available a few years ago now have widespread usage. Adding to the complexity are construction variables such as weather, mix delivery times, finishing practices, and pavement opening schedules. Mixture materials, mix design, and pavement construction are not isolated steps in the concrete paving process. Each affects and is affected by the other in ways that determine overall pavement quality and long-term performance. Equipment and procedures commonly used to test concrete materials and concrete pavements have not changed in decades, leaving serious gaps in our ability to understand and control the factors that determine concrete durability. The concrete paving community needs tests that will adequately characterize the materials, predict interactions, and monitor the properties of the concrete.

Efficacy of clarithromycin versus that of clindamycin for single-dose prophylaxis of experimental streptococcal endocarditis.

Clarithromycin is compared with clindamycin for single-dose prophylaxis of streptococcal endocarditis in rats. Human-like kinetics of the two antibiotics prevented endocarditis in animals challenged with both small and large amounts of bacterial inocula. Clarithromycin was marginally superior to clindamycin against small amounts of inocula. Clarithromycin may be considered for endocarditis chemoprophylaxis in human.

Development, optimization, and validation of novel anti-TEM1/CD248 affinity agent for optical imaging in cancer.

Tumor Endothelial Marker-1 (TEM1/CD248) is a tumor vascular marker with high therapeutic and diagnostic potentials. Immuno-imaging with TEM1-specific antibodies can help to detect cancerous lesions, monitor tumor responses, and select patients that are most likely to benefit from TEM1-targeted therapies. In particular, near infrared(NIR) optical imaging with biomarker-specific antibodies can provide real-time, tomographic information without exposing the subjects to radioactivity. To maximize the theranostic potential of TEM1, we developed a panel of all human, multivalent Fc-fusion proteins based on a previously identified single chain antibody (scFv78) that recognizes both human and mouse TEM1. By characterizing avidity, stability, and pharmacokinectics, we identified one fusion protein, 78Fc, with desirable characteristics for immuno-imaging applications. The biodistribution of radiolabeled 78Fc showed that this antibody had minimal binding to normal organs, which have low expression of TEM1. Next, we developed a 78Fc-based tracer and tested its performance in different TEM1-expressing mouse models. The NIR imaging and tomography results suggest that the 78Fc-NIR tracer performs well in distinguishing mouse- or human-TEM1 expressing tumor grafts from normal organs and control grafts in vivo. From these results we conclude that further development and optimization of 78Fc as a TEM1-targeted imaging agent for use in clinical settings is warranted.

Materials and Mix Optimization Procedures for PCC Pavements, March 2006

Severe environmental conditions, coupled with the routine use of deicing chemicals and increasing traffic volume, tend to place extreme demands on portland cement concrete (PCC) pavements. In most instances, engineers have been able to specify and build PCC pavements that met these challenges. However, there have also been reports of premature deterioration that could not be specifically attributed to a single cause. Modern concrete mixtures have evolved to become very complex chemical systems. The complexity can be attributed to both the number of ingredients used in any given mixture and the various types and sources of the ingredients supplied to any given project. Local environmental conditions can also influence the outcome of paving projects. This research project investigated important variables that impact the homogeneity and rheology of concrete mixtures. The project consisted of a field study and a laboratory study. The field study collected information from six different projects in Iowa. The information that was collected during the field study documented cementitious material properties, plastic concrete properties, and hardened concrete properties. The laboratory study was used to develop baseline mixture variability information for the field study. It also investigated plastic concrete properties using various new devices to evaluate rheology and mixing efficiency. In addition, the lab study evaluated a strategy for the optimization of mortar and concrete mixtures containing supplementary cementitious materials. The results of the field studies indicated that the quality management concrete (QMC) mixtures being placed in the state generally exhibited good uniformity and good to excellent workability. Hardened concrete properties (compressive strength and hardened air content) were also satisfactory. The uniformity of the raw cementitious materials that were used on the projects could not be monitored as closely as was desired by the investigators; however, the information that was gathered indicated that the bulk chemical composition of most materials streams was reasonably uniform. Specific minerals phases in the cementitious materials were less uniform than the bulk chemical composition. The results of the laboratory study indicated that ternary mixtures show significant promise for improving the performance of concrete mixtures. The lab study also verified the results from prior projects that have indicated that bassanite is typically the major sulfate phase that is present in Iowa cements. This causes the cements to exhibit premature stiffening problems (false set) in laboratory testing. Fly ash helps to reduce the impact of premature stiffening because it behaves like a low-range water reducer in most instances. The premature stiffening problem can also be alleviated by increasing the water–cement ratio of the mixture and providing a remix cycle for the mixture.

Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice.

In vitro studies suggested that sub-millisecond pulses of radiation elicit less genomic instability than continuous, protracted irradiation at the same total dose. To determine the potential of ultrahigh dose-rate irradiation in radiotherapy, we investigated lung fibrogenesis in C57BL/6J mice exposed either to short pulses (≤ 500 ms) of radiation delivered at ultrahigh dose rate (≥ 40 Gy/s, FLASH) or to conventional dose-rate irradiation (≤ 0.03 Gy/s, CONV) in single doses. The growth of human HBCx-12A and HEp-2 tumor xenografts in nude mice and syngeneic TC-1 Luc(+) orthotopic lung tumors in C57BL/6J mice was monitored under similar radiation conditions. CONV (15 Gy) triggered lung fibrosis associated with activation of the TGF-β (transforming growth factor-β) cascade, whereas no complications developed after doses of FLASH below 20 Gy for more than 36 weeks after irradiation. FLASH irradiation also spared normal smooth muscle and epithelial cells from acute radiation-induced apoptosis, which could be reinduced by administration of systemic TNF-α (tumor necrosis factor-α) before irradiation. In contrast, FLASH was as efficient as CONV in the repression of tumor growth. Together, these results suggest that FLASH radiotherapy might allow complete eradication of lung tumors and reduce the occurrence and severity of early and late complications affecting normal tissue.