Cone-beam CT with megavoltage beams and an amorphous silicon electronic portal imaging device: potential for verification of radiotherapy of lung cancer

We investigate the potential of megavoltage (MV) cone-beam CT with an amorphous silicon electronic portal imaging device (EPID) as a tool for patient position verification and tumor/organ motion studies in radiation treatment of lung tumors. We acquire 25 to 200 projection images using a 22 x 29 cm EPID. The acquisition is automatic and requires 7 minutes for 100 projections; it can be synchronized with respiratory gating. From these images, volumetric reconstruction is accomplished with a filtered backprojection in the cone-beam geometry. Several important prereconstruction image corrections, such as detector sag, must be applied. Tests with a contrast phantom indicate that differences in electron density of 2% can be detected with 100 projections, 200 cGy total dose. The contrast-to-noise ratio improves as the number of projections is increased. With 50 projections (100 cGy), high contrast objects are visible, and as few as 25 projections yield images with discernible features. We identify a technique of acquiring projection images with conformal beam apertures, shaped by a multileaf collimator, to reduce the dose to surrounding normal tissue. Tests of this technique on an anthropomorphic phantom demonstrate that a gross tumor volume in the lung can be accurately localized in three dimensions with scans using 88 monitor units. As such, conformal megavoltage cone-beam CT can provide three-dimensional imaging of lung tumors and may be used, for example, in verifying respiratory gated treatments.     

Permanent impairment of embryo development by hydrosalpinges

Recent reports suggest a deleterious effect of hydrosalpinges on pregnancy outcome for in-vitro fertilization (IVF) and improvement following surgical treatment. We compared the effect of hydrosalpinx on pregnancy outcome in 286 patients having 348 IVF cycles and followed the development of untransferred embryos for 7 days to determine if hydrosalpinges affect oocyte quality or embryo development. The delivery rate per retrieval was significantly lower for patients with hydrosalpinx, but was restored by surgical treatment to that of patients without hydrosalpinx. However, the implantation rate per embryo transferred and normal blastulation of untransferred embryos, which were significantly decreased in patients with hydrosalpinx, and growth arrest and degeneration of untransferred embryos, which were significantly increased compared to patients without hydrosalpinx, were not restored by surgical treatment of hydrosalpinges. We conclude that surgical treatment of hydrosalpinges decreases early pregnancy loss and improves pregnancy outcome, possibly by diminishing reversible deleterious effects exerted on the endometrium. As we have seen in our laboratory, hydrosalpinges may have a permanent negative influence on ovarian function, follicular development and oocyte quality since implantation of transferred embryos and normal blastulation of untransferred embryos remain low, and in-vitro growth arrest and degeneration remain high despite surgical treatment of hydrosalpinges.      

Do Treatment Plans Matter? Moving From Recommendations to Action

We investigated whether a service-planning document outlining recommendations for what providers should address in treatment (i.e., targets) and the associated clinical techniques they should employ (i.e., practices) influenced the targets and practices that providers reported actually implementing during the subsequent treatment episode. Participants included 94 youths ages 4 to 17 (M = 13.57, SD = 3.59) who received community-based mental health services from the Hawai'i Child and Adolescent Mental Health Division. Data on targets and practices were compared across initial Mental Health Treatment Plans and Monthly Treatment and Progress Summaries. Data were analyzed using two-level, generalized mixed effects models with two-way cross-classification or linear mixed effects models. Providers were more likely to report the use of targets and practices in treatment if they were included within the treatment plan. In addition, the more closely targets addressed during treatment followed the recommended targets from the treatment plan, the more closely implemented practices followed the recommended practices listed in the treatment plan. Furthermore, as providers shifted their focus to different targets, a shift in their use of practices was also evident over time. Last, practices for which there is demonstrated efficacy for particular targets were more likely to be used. Service planning documents appear to help organize care; however, results also suggest possible limitations to the current system. These findings highlight potential areas for improvement in planning and care delivery.     

Hemoglobin substitute and cardiopulmonary bypass

The effects of diaspirin crosslinked hemoglobin (DCLHb, Baxter Health Care Corp., Round Lake, IL) on oxygen exchange in the setting of cardiopulmonary bypass (CPB) are unknown. Six calves (71.2 +/- 1.3 kg) were connected to CPB by jugular venous and carotid arterial cannulation for 5 hours. Each 1 hour period included 45 min of partial CPB (mean flow rate of 50 ml/kg per min) followed by 15 min without CPB, at the end of which 500 ml of blood were substituted for with either 500 ml of hydroxyethyl starch (Haes; n = 3) or 500 ml of DCLHb (n = 3). A total of 2 liters of blood was, thus, exchanged (28 ml/kg of blood substitute). Values are expressed as mean +/- 1 SD. Analysis of variance for repeated measurements was used. The cardiac output (CO) values at 1 h, 3 h, and 5 h were in the Haes group: 5.7 +/- 2, 6.7 +/- 2.5, and 7.7 +/- 2.5L/min, and in the DCLHb group: 5.7 +/- 0.6, 4 +/- 1, and 4.7 +/- 1.2 L/min, respectively. The arteriovenous oxygen content difference (Ca-Cvo2) values at 1 h, 3 h, and 5 h were in the Haes group: 4.6 +/- 1, 3.3 +/- 1.5, and 3.5 +/- 1.5 ml/dl, and in the DCLHb group: 4.9 +/- 0.6, 7.4 +/- 0.7, and 6.6 +/- 0.6 ml/dl, respectively. The oxygen consumption (Vo2) values at 1 h, 3 h, and 5 h were in the Haes group: 244 +/- 29, 198 +/- 58, and 249 +/- 42 ml/min, and in the DCLHb group: 273 +/- 28, 296 +/- 75, and 306 +/- 65 ml/min, respectively. CO and Ca-Cvo2 showed a significant difference (p < 0.01), whereas Vo2 did not (p = 0.52). In the DCLHb group of this CPB animal model, the cardiac output is lower and the arteriovenous oxygen content difference higher than in the Haes group, allowing for preserved oxygen consumption.     

Evaluation of Murex CMV DNA Hybrid Capture Assay for Detection and Quantitation of Cytomegalovirus Infection in Patients following Allogeneic Stem Cell Transplantation

Murex hybrid capture DNA assay (HCS) is a solution hybridization antibody capture assay for detection and quantitation of cytomegalovirus (CMV) DNA in leukocytes. To determine whether CMV HCS is sensitive enough to initiate and monitor antiviral therapy after allogeneic stem cell transplantation (SCT), 51 consecutive SCT recipients were prospectively screened for the appearance of CMV infection by HCS, PCR, and culture assays from blood samples. Preemptive antiviral therapy was initiated after the second positive PCR result in all patients, as previously reported, and HCS was not considered for clinical decision making. A total of 417 samples were analyzed. Of these, 21 samples were found to be positive by PCR and HCS, 88 samples were PCR positive but HCS negative, and 308 were negative by both assays. Concordance of results between PCR and HCS and between HCS and blood culture was observed in 78.9 and 95.9% of the samples assayed, respectively. PCR was found to be more sensitive than HCS, and HCS was more sensitive than the blood culture assay (P < 0.0001). Four patients with symptomatic CMV infection were PCR positive prior to the onset of CMV-related symptoms, whereas HCS detected CMV DNA in three patients prior to and one at onset of CMV disease. The numbers of genomes per milliliter of blood were higher in patients with symptomatic CMV infection than in those with asymptomatic CMV infection (P = 0.06). None of the HCS-negative patients developed CMV disease. Thus, all patients with CMV disease were correctly identified by HCS; however, the lower sensitivity limit of the HCS assay may still be insufficient to allow diagnosis of CMV infection early enough to prevent CMV disease in patients following allogeneic SCT.     

Potential target sites in peripheral tissues for excitatory neurotransmission and excitotoxicity

Glutamate receptors (GluRs) are ubiquitously present in the central nervous system (CNS) as the major mediators of excitatory neurotransmission and excitotoxicity. Neural injury associated with trauma, stroke, epilepsy, and many neurodegenerative diseases such as Alzheimer's, Huntington's, and Parkinson's diseases and amyotrophic lateral sclerosis may be mediated by excessive activation of GluRs. Neurotoxicity associated with excitatory amino acids encountered in food, such as domoic acid and monosodium glutamate, has also been linked to GluRs. Less is known about GluRs outside the CNS. Recent observations suggest that several subtypes of GluRs are widely distributed in peripheral tissues. Using immunochemical and molecular techniques, the presence of GluR subtypes was demonstrated in the rat and monkey heart, with preferential distribution within the conducting system, nerve terminals, and cardiac ganglia. GluR subtypes NMDAR 1, GluR 2/3, and mGluR 2/3 are also present in kidney, liver, lung, spleen, and testis. Further investigations are needed to assess the role of these receptors in peripheral tissues and their importance in the toxicity of excitatory compounds. Therefore, food safety assessment and neurobiotechnology focusing on drugs designed to interact with GluRs should consider these tissues as potential target/effector sites.     

Chorioallantoic membrane angiogenesis model for tissue engineering: a new twist on a classic model

Tissue-engineering (TE) applications include the isolation, culture, and seeding of cells into a suitable matrix or scaffold before in vivo transplantation. After transplantation, vascularization of the scaffold is a principal limiting factor for cell viability for the first 6-8 days posttransplantation. A model for systematic analysis of this process has been developed. Fertilized White Leghorn eggs were incubated (at 37.8 degrees C in 60% relative humidity) and opened on day 3 of incubation. Preadipocyte-seeded fibrin constructs were implanted in a specially designed plastic cylinder and placed through the opening on the surface of the chorioallantoic membrane (CAM) on day 8 of incubation. Vascularization of the constructs by chorioallantoic blood vessels was assessed for up to 8 days posttransplantation. The survival rate for embryos receiving transplanted constructs was about 90%. Histology confirmed transplant cell viability at day 4 posttransplantation and vascularization of the constructs by avian endothelial cells began at this time. A new in vivo model to study the effect of angiogenesis in TE constructs, including assessments of viability, proliferation, and differentiation of transplanted cells and biomaterial properties, is presented. Advantages include easy access to the vascular network of the CAM, lack of immunocompetence, low costs, and avoidance of animal experiments.     

Antithrombotic properties of trillium coated connectors

Trillium coating (Medtronic Inc., Minneapolis, MN) offers, in addition to the presence of heparin, endothelium-like properties of its negatively charged surface. Its thromboresistant properties on coated connectors are tested here and compared with uncoated standard connectors, as well as with the Carmeda BioActive surface (CBAS) heparin surface coating. A partial cardiopulmonary bypass bovine model (body weight 68 +/- 5 kg) was selected, and the surfaces were exposed to the blood stream (pump flow 3.5 L/min) for up to 350 minutes without systemic heparinization. Thereafter, another set of samples was exposed to stagnant blood for 20 minutes. Besides hemodynamic, hematologic, and biochemical analyses, the macroscopic appearance of 45 blood exposed surface samples were graded semiquantitatively on a scale of 0 to 10: no macroscopic deposits = grade 0, one spot (1 mm diameter) = grade 1, two spots = grade 2, five or more spots = grade 5, 10% of the surface covered with clots = grade 6, 100% covered = grade 10. When exposed to blood flow, Trillium and CBAS coatings showed a statistically significant (p = 0.03) better thromboresistance (score: 0 +/- 0 for both) than uncoated connectors (score: 0.8 +/- 1.5) in this nonheparinized model. The same holds true when the connectors were exposed to stagnant blood (score: 0 +/- 0 for both coatings vs 4.3 +/- 2.8 for controls; p = 0.03). Therefore, Trillium coating exhibits significant antithrombotic properties that outperform standards for connectors used in clinical perfusion.     

Lymph Node Mesenchymal and Endothelial Stromal Cells Cooperate via the RANK-RANKL Cytokine Axis to Shape the Sinusoidal Macrophage Niche

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Is fecundability associated with month of birth? An analysis of 19th and early 20th century family reconstitution data from The Netherlands

The relationship between fecundability and month of birth was investigated in a cohort of 1526 women who married between 1802 and 1929, using only women whose first marriage occurred before the age of 35 years. On the basis of their time to pregnancy (TTP, calculated as time between wedding and first birth minus gestational length), women were categorized into two groups: fecunds (TTP up to 12 months or prenuptial conceptions, n = 1348) and subfecunds (TTP >18 months, n = 118). By use of logistic regression, cosinor functions with a period of 1 year or 6 months and variable shift and amplitude were fitted through the monthly odds of subfecunds versus fecunds. The best fitting curve was unimodal, with a zenith in September (P = 0.13 for H0: no differences). Exclusion of childless women (n = 36, minimum follow-up 5 years) from the subfecunds led to a similar curve (P < 0.01), while childless women, as compared with fecunds, showed a birth distribution that was best represented with a bimodal curve with zeniths in January and July (P = 0.06). This study provides evidence for the existence of differences in fecundability by month of birth. The cause of this relationship is unclear, but may lie in a melatonin-dependent circannual variability of the quality of the oocyte.