Patient dose considerations for routine megavoltage cone-beam CT imaging

Megavoltage cone-beam CT (MVCBCT), the recent addition to the family of in-room CT imaging systems for image-guided radiation therapy (IGRT), uses a conventional treatment unit equipped with a flat panel detector to obtain a three-dimensional representation of the patient in treatment position. MVCBCT has been used for more than two years in our clinic for anatomy verification and to improve patient alignment prior to dose delivery. The objective of this research is to evaluate the image acquisition dose delivered to patients for MVCBCT and to develop a simple method to reduce the additional dose resulting from routine MVCBCT imaging. Conventional CT scans of phantoms and patients were imported into a commercial treatment planning system (TPS: Phillips, Pinnacle) and an arc treatment mimicking the MVCBCT acquisition process was generated to compute the delivered acquisition dose. To validate the dose obtained from the TPS, a simple water-equivalent cylindrical phantom with spaces for MOSFETs and an ion chamber was used to measure the MVCBCT image acquisition dose. Absolute dose distributions were obtained by simulating MVCBCTs of 9 and 5 monitor units (MU) on pelvis and head and neck patients, respectively. A compensation factor was introduced to generate composite plans of treatment and MVCBCT imaging dose. The article provides a simple equation to compute the compensation factor. The developed imaging compensation method was tested on routinely used clinical plans for prostate and head and neck patients. The quantitative comparison between the calculated dose by the TPS and measurement points on the cylindrical phantom were all within 3%. The dose percentage difference for the ion chamber placed in the center of the phantom was only 0.2%. For a typical MVCBCT, the dose delivered to patients forms a small anterior-posterior gradient ranging from 0.6 to 1.2 cGy per MVCBCT MU. MVCBCT acquisitions in the pelvis and head and neck areas deliver slightly more dose than current portal imaging but render soft tissue information for positioning. Overall, the additional dose from daily 9 MU MVCBCTs of prostate patients is small compared to the treatment dose (<4%). Dose-volume histograms of compensated plans for pelvis and head and neck patients imaged daily with MVCBCT showed no additional dose to the target and small increases at low doses. The results indicate that the dose delivered for MVCBCT imaging can be precisely calculated in the TPS and therefore included in the treatment plan. This allows simple plan compensations, such as slightly reducing the treatment dose, to minimize the total dose received by critical structures from daily positioning with MVCBCT. The proposed compensation factor reduces the number of MU per treatment beam per fraction. Both the number of fractions and the beam arrangement are kept unchanged. Reducing the imaging volume in the cranio-caudal direction can further reduce the dose delivered for MVCBCT. This is a useful feature to eliminate the imaging dose to the eyes or to focus on a specific region of interest for alignment.     

Effect of meningococcal endotoxin in a rabbit model of shock.

Endotoxin in the form of a lipooligosaccharide (LOS) plays a key role in the development of shock in meningococcal sepsis. To examine hemodynamic and biochemical alterations during meningococcal endotoxic shock, we established a rabbit model. Thirty-nine rabbits, weighing 2.5-4.4 kg, were studied. After anesthesia with intramuscular ketamine (20 mg/kg) and xylazine (4 mg/kg), femoral venous and arterial catheters were inserted. Control animals received only saline, while rabbits in each of four additional groups were given LOS in 10-fold increments from 0.1 microgram/kg to 100 microgram/kg. Mean arterial pressure (MAP), heart rate (HR), respirations (RR), temperature (T), urine output, and arterial blood gases (pH, PCO2, PO2, and bicarbonate) were determined at baseline and hourly. Endotoxin levels and TNF levels were measured at 30, 60, 120, 180, 240, 300, and 360 min post-LOS. Survival was recorded. One-way analysis of variance (ANOVA) and the Scheffe procedure, paired samples t-test, two-tailed t-test, and Fisher's exact test were used. Pearson's coefficients were calculated. Animals receiving meningococcal LOS developed tachycardia and compensated metabolic acidosis with an initially normal pH and MAP. With progression of the shock state, the pH decreased and hypotension ensued. Maximal levels of endotoxin were measured 30 min after LOS injection and declined during the ensuing 6 hr. TNF rose from undetectable to markedly elevated levels and peaked at 60-120 min post-LOS. Increasing the amount of injected endotoxin produced more profound degrees of shock until a dose of 10.0 micrograms/kg was reached. There was no correlation between serum TNF at 60 min and survival at 6 hr or 24 hr.(ABSTRACT TRUNCATED AT 250 WORDS)     

Synergistic myelopoietic actions in vivo after administration to mice of combinations of purified natural murine colony-stimulating factor 1, recombinant murine interleukin 3, and recombinant murine granulocyte/macrophage colony-stimulating factor.

Combinations of low dosages of purified murine hematopoietic colony-stimulating factors (CSFs)--L-cell CSF type 1 (CSF-1), recombinant interleukin 3 (IL-3), and recombinant granulocyte/macrophage CSF (GM-CSF)--were compared with single CSFs for their influence on the cycling rates and numbers of bone marrow granulocyte/macrophage, erythroid, and multipotential progenitor cells in vivo in mice pretreated with human lactoferrin. Lactoferrin was used to enhance detection of the stimulating effects of exogenously administered CSFs. Concentrations of CSFs that were not active in vivo when given alone were active when administered together with other types of CSF. The concentrations of CSF-1, IL-3, and GM-CSF needed to increase progenitor cell cycling rates were reduced by factors of 40-200, 10-50, and 40- greater than 400, respectively; the concentrations needed to increase progenitor cell numbers were reduced by factors of 40-500 (CSF-1), 20-80 (IL-3), and greater than 40- greater than 200 (GM-CSF) when these forms of CSFs were administered in combination with low dosages of one of the other forms of CSFs. The results demonstrate that different CSFs can synergize when administered in vivo to increase the cycling rates and numbers of marrow hematopoietic progenitor cells. These findings may be of relevance physiologically to the regulation of myeloid blood cell production by CSFs.     

Health care costs and costs associated with changes in work productivity among persons with systemic lupus erythematosus

Objective

To estimate health care costs and costs associated with changes in work productivity among persons with systemic lupus erythematosus (SLE) in the US.

Methods

Data were derived from the University of California, San Francisco Lupus Outcomes Study. Participants provided information on their health care resource use and employment. Cost estimates were derived for both direct health care costs and costs related to changes in work productivity. Direct health care costs included costs for hospitalizations, emergency department services, physician visits, outpatient surgical procedures, dialysis, and medications. Productivity costs were estimated by measuring changes in hours of work productivity since diagnosis of SLE; these estimates were also compared with normal US population data.

Results

For the total population of participants, the mean annual direct cost was $12,643 (2004 US dollars). The mean annual productivity cost for subjects of employment age (≥18 and <65 years) was $8,659. The mean annual total cost (direct and productivity) for subjects of employment age was $20,924. Regression results showed that greater disease activity, longer disease duration, and worse physical and mental health were significant predictors of higher direct costs; older age predicted lower direct costs. Older age, greater disease activity, and worse physical and mental health status were significant predictors of higher costs due to changes in work productivity.

Conclusion

Both direct health care costs and costs associated with changes in work productivity are substantial and both represent important contributors to the total costs associated with SLE.     

Parental Bonding Reports of Clients with Obsessive–Compulsive Disorder and Agoraphobia

The study was designed to address two broad purposes: (a) to investigate further the reliability and validity of the Parental Bonding Instrument (PBI) and (b) to examine the relationship of parental warmth and overprotection to specific anxiety disorders and their symptoms, anxious personality traits, and social functioning. The PBI was administered, before and after exposure treatment, to an outpatient sample of 52 adults with obsessive–compulsive disorder and 35 with panic disorder with agoraphobia, and to their parents (n=42), if they resided with the patient. PBI scores remained stable despite improvement in symptom severity and mood. Parents' and patients' recollections of the parents' behaviour towards the patient did not agree. According to patients, their parents most often raised them using affectionless control, whereas parents most often rated themselves as having provided optimal parenting. Patients' PBI scores were not related to type or severity of anxiety disorder. However, reports of poorer parenting were associated with worse social adjustment and higher levels of anxious personality disorder characteristics.     

Glucocorticoids and immune responses

We describe a series of investigations on mechanisms of antiinflammatory and immunosuppressive actions of glucocorticoids. Glucocorticoid receptors and primary mechanisms of action have been studied with isolated rat thymus cells. When added to these cells glucocorticoids immediately form cytoplasmic hormone-receptor complexes which after activation bind to the nuclei where they apparently induce mRNA for specific proteins that rapidly inhibit glucose transport and acetate incorporation into lipids. Protein and RNA metabolism are inhibited more slowly and eventually the cells die. With normal peripheral human lymphocytes, similar but slower effects are produced. A dramatic increase in receptor sites per cell is seen in lymphocytes stimulated with concanavalin A or antigen. This increase is probably associated with preparation for mitosis. We do not find, contrary to widespread belief, that these stimulated cells are insensitive to glucocorticoids. Such insensitivity has been invoked to explain the insensitivity to glucocorticoid suppression of secondary compared to primary immune responses. An alternative explanation emerges from our experiments with T-cell growth factor. T-cell growth factor, produced by mitogen or antigen stimulated spleen cells, is necessary for the proliferation of T-lymphocytes in culture and may be responsible for clonal expansion of antigen-responsive T-cells. Treatment of Con A-stimulated rat spleen cells or human peripheral mononuclear cells with 100 nM dexamethasone inhibits the production of the growth factor by 95%. This effect is specific for glucocorticoids. Addition of T-cell growth factor completely reverses the inhibition by glucocorticoid of mitogen-induced blastogenesis. We propose that the inhibitory actions of glucocorticoids on antigen- or mitogen-induced T-cell blastogenesis are related to inhibition of production of T-cell growth factor and that the reason the primary immune response is more sensitive to glucocorticoids is that by inhibiting production of T-cell growth factor, glucocorticoids block the clonal expansion necessary to amplify the primary response. We have also studied effects of glucocorticoids on Fc receptors, which play important roles in phagocytosis and other aspects of immune responses. Treatment of the human progranulocytic cell line HL-60 with dexamethasone for 72 hours reduces by 35-50% the Fc receptors per cell with no effect on cell viability or proliferation and slight increase in leucine incorporation. The effect is specific for glucocorticoids. These findings indicate that an important component in glucocorticoid-induced immunosuppression may be a reduction in Fc receptors, and with the results on T-cell growth factor, suggest that glucocorticoids regulate immune processes via effects on lymphokines and other immunologically important proteins.     

Abstracts of Articles on Nutrition and Bone Loss

Objective: To identify if particular foods or food groups may be associated with obesity in children and adolescents and to determine if consuming food away from home (FAFH) has an effect on the nutritional quality of their diets.

Design: One-year cross-sectional study.

Setting/Subjects: The obese subjects (n = 91) were on the waiting list for a hospital-based weight control treatment program. The non-obese subjects (n = 90) were recruited from community advertisements.

Measures of Outcome: Information on food intake was obtained using the dietary history method by a Registered Dietitian. Body fat was determined by bioelectrical impedance analysis.

Results: Obese children and adolescents consumed significantly more servings of meat and alternatives, grain products, FAFH, sugar-sweetened drinks and potato chips which contributed to a higher calorie, fat and sugar intake compared to non-obese children and adolescents. Sugar-sweetened drinks were only significantly greater in boys. The consumption of meat servings, sugar-sweetened drinks and FAFH was positively correlated with percent body fat. The frequency of food consumed outside of the Canada’s Food Guide To Healthy Eating was not different between the two groups.

Conclusions: Obese children and adolescents need to limit their access to food consumed away from home and sugar-sweetened drinks as there is a relationship between these foods and body fatness.     

The Halifax explosion and the birth of a surgical specialty—myth or reality

The work of Dr William E. Ladd after a devastating explosion in Halifax in 1917 has been credited with his decision to devote his subsequent career to the betterment of surgical care for children. He has been recognized as the “father of pediatric surgery” in North America. The authors present a written refutation of this causal association by Dr Ladd.