MIRD pamphlet No. 17: the dosimetry of nonuniform activity distributions--radionuclide S values at the voxel level. Medical Internal Radiation Dose Committee

The availability of quantitative three-dimensional in vivo data on radionuclide distributions within the body makes it possible to calculate the corresponding nonuniform distribution of radiation absorbed dose in body organs and tissues. This pamphlet emphasizes the utility of the MIRD schema for such calculations through the use of radionuclide S values defined at the voxel level. The use of both dose point-kernels and Monte Carlo simulation methods is also discussed. PET and SPECT imaging can provide quantitative activity data in voxels of several millimeters on edge. For smaller voxel sizes, accurate data cannot be obtained using present imaging technology. For submillimeter dimensions, autoradiographic methods may be used when tissues are obtained through biopsy or autopsy. Sample S value tabulations for five radionuclides within cubical voxels of 3 mm and 6 mm on edge are given in the appendices to this pamphlet. These S values may be used to construct three-dimensional dose profiles for nonuniform distributions of radioactivity encountered in therapeutic and diagnostic nuclear medicine. Data are also tabulated for 131I in 0.1-mm voxels for use in autoradiography. Two examples illustrating the use of voxel S values are given, followed by a discussion of the use of three-dimensional dose distributions in understanding and predicting biologic response.     

Pathogenicity of Theileria parva is influenced by the host cell type infected by the parasite

Theileria parva has been shown to infect and transform B cells and T cells at similar frequencies in vitro. However, the majority of parasitized cells in the tissues of infected cattle are alpha/beta T cells. The aim of this study was to determine whether the cell type infected with T. parva influenced the pathogenicity of the parasite. The initial approach, which involved inoculation of cattle with autologous cloned cell lines of different phenotypes, failed to resolve the issue, because of prolonged period of culture required to clone and characterize the cell lines resulted in attenuation of the cells. As an alternative approach, cattle were inoculated with purified populations of autologous cells that had been incubated in vitro with T. parva sporozoites for 48 h. As few as 3 x 10(4) peripheral blood mononuclear cells (PBMC) treated in this way were found to produce severe clinical reactions with high levels of parasitosis. Infections of similar severity were produced with purified populations of CD2+, CD4+, and CD8+ T cells. By contrast, infected B cells gave rise to mild self-limiting infections even when administered at a 10-fold-higher dose. In animals that received infected CD4+ or CD8+ T cells, the parasitized cells in the lymph nodes on day 11 of infection were all within the CD4+ and CD8+ populations, respectively, indicating that there had been minimal transfer of the parasite between cell types. Phenotypic analyses of cultures of PBMC infected in vitro with saturating concentrations of sporozoites revealed that parasitized B cells were abundant in the cultures after 1 week but were subsequently overgrown by T cells. The results of these experiments indicate that the cell type infected by T. parva influences the pathogenicity of the parasite.     

Causes and treatment of bone pain of malignant origin

Pain relief has been one of the oldest and most important duties of the physician. There has been little change with regard to this obligation of all caregivers. One-third of patients with advanced cancer will develop clinically relevant skeletal metastases and chronic pain during the course of their disease. All physicians involved in the treatment of cancer patients should know the basic principles of pain treatment. These are described in the following article with special regard to bone pain of malignant origin. Correct assessment of pain intensity and frequency, as well as of the probable causes of pain, and the administration of adequate analgesic treatment should achieve satisfactory results in the vast majority of patients. Every physician should obtain detailed knowledge of the indications and adequate administration of pain-killing therapy as well as possible adverse effects and their successful treatment. It is important in particular to concentrate on a few nonsteroidal anti-inflammatory drugs (NSAIDs) as well as opiates. Knowledge of adequate doses, maximal recommended daily doses, pharmacological properties, important adverse effects and interactions is essential for success in the daily routine. Only by selecting 2 or 3 drugs from each step in the analgesic ladder (WHO) will the nonspecialised physician obtain sufficient experience for optimal analgesia. Physicians should also not hesitate to contact other specialists (medical oncologists, radiotherapists, neurosurgeons, anaesthesiologists and others) in order to maximise benefit for an individual patient.     

Does coronary artery screening by electron beam computed tomography motivate potentially beneficial lifestyle behaviors?

We evaluated the extent to which cardiovascular risk-reducing behaviors are initiated as a result of knowledge of newly detected coronary artery disease, based on test results from noninvasive electron beam computed tomography (EBCT). A total of 703 men and women, aged 28 to 84 years, asymptomatic and without prior coronary disease, who had a baseline EBCT coronary artery scan and basic medical history and risk factor information completed a follow-up survey questioning them about health behaviors undertaken since their scan. Baseline calcium scores were significantly higher in those who subsequently reported consulting with a physician, or reported new hospitalization, coronary revascularization, beginning aspirin usage, blood pressure medications, cholesterol-lowering therapy, decreasing dietary fat, losing weight, beginning vitamin E, and under more worry (all p <0.01). Other factors, including reducing time worked, obtaining life insurance, losing employment, increased work absenteeism, increasing exercise, or stopping smoking were not associated with coronary calcium. In logistic regression, after adjusting for age, gender, pre-existing high cholesterol, high blood pressure, cigarette smoking, and a positive family history of coronary disease, the natural log of total calcium score remained associated with new aspirin usage, new cholesterol medication, consulting with a physician, losing weight, decreasing dietary fat, new coronary revascularization (all p <0.01), but also new hospitalization (p <0.05) and increased worry (p <0.001). The results suggest that potentially important risk-reducing behaviors may be reinforced by the knowledge of a positive coronary artery scan, independent of preexisting coronary risk factor status.     

Port-site metastases. Impact of local tissue trauma and gas leakage

OBJECTIVE: To determine whether selective 5-lipoxygenase (5-LO) inhibition decreases expression of adhesion molecules (beta2 integrins) on systemic neutrophils, decreases neutrophil infiltration in ischemic flap tissue, and improves flap survival. DESIGN: A randomized, controlled study of 91 adult female Hartley guinea pigs divided into 3 survival groups, 4 neutrophil assay groups, 1 sham group, and 1 control group. Ischemia of varying duration and reperfusion was induced in island flank skin flaps. The treated groups received zileuton, a 5-LO inhibitor, orally during flap ischemia. After reperfusion, systemic neutrophil receptor expression, neutrophil infiltration, and flap survival were measured. Surface receptor molecules on neutrophils from whole blood samples obtained via transcardiac puncture were analyzed using monoclonal antibodies and cell-associated fluorescence. Neutrophil infiltration into a distal 1 cm2 of flap tissue was assessed using myeloperoxidase antibodies. Flap survival was determined within 7 days of surgery. RESULTS: Untreated flaps with 10 hours of ischemia underwent total necrosis. Treated 2- and 10-hour ischemic flaps survived intact. A significant main effect of the drug treatment was detected using analysis of variance (P<.001). Neutrophil receptor detection in the untreated groups undergoing 2 and 10 hours of ischemia was significantly increased compared with that in the treated groups with the same ischemia times. Skin neutrophil infiltration was significantly decreased in the treated groups. CONCLUSIONS: Systemic administration of a 5-LO inhibitor is effective in reducing ischemia-reperfusion injury in flap tissue. Our data indicate that there is a significant reduction in neutrophil receptor expression with administration of 5-LO, reducing the priming of systemic neutrophils from circulating cytokines.     

A high-fat diet influences insulin-stimulated posttransport muscle glucose metabolism in rats

Because of a failure to detect significant quantities of intracellular glucose, it has been generally accepted that transport rather than phosphorylation is the rate-limiting process of muscle glucose metabolism under most (but not all) physiological conditions. Here, we have measured tissue free levels of the glucose analog 2-deoxy-D-glucose (2DG) in red quadriceps muscle of rats fed a high-fat diet (59% of energy from fat) for 3 weeks, to identify the barrier to insulin-stimulated glucose uptake previously seen in such animals. Measurements were performed on pentobarbital-anesthetized rats following exogenous infusion of radiolabeled 2DG. A glucose clamp was used to maintain plasma insulin at high physiological levels (approximately 120 mU/L). Three other treatment groups representing normal insulin action (chow-fed), extreme glucose uptake (maximal insulin stimulation + hyperglycemia), and insulin resistance with elevated free intracellular glucose (epinephrine infusion) were also studied for comparison. In chow-fed animals, no muscle free 2DG was detected, confirming transport as the rate-limiting process. In fat-fed animals, a significant elevation in muscle free 2DG was observed (P < .01 v chow-fed controls). The elevation was similar in magnitude to that in epinephrine-infused rats, and implied a limitation of insulin action at a posttransport step. This result was confirmed with a more complex modeling analysis. We conclude that posttransport steps influence insulin-stimulated in vivo muscle glucose metabolism in long-term high-fat-fed rats.