Dose profiles and x-ray energy optimization for microbeam radiation therapy by high-dose, high resolution dosimetry using Sm-doped fluoroaluminate glass plates and Monte Carlo transport simulation.

Microbeam radiation therapy (MRT) utilizes highly collimated synchrotron generated x-rays to create narrow planes of high dose radiation for the treatment of tumors. Individual microbeams have a typical width of 30-50 µm and are separated by a distance of 200-500 µm. The dose delivered at the center of the beam is lethal to cells in the microbeam path, on the order of hundreds of Grays (Gy). The tissue between each microbeam is spared and helps aid in the repair of adjacent damaged tissue. Radiation interactions within the peak of the microbeam, such as the photoelectric effect and incoherent (atomic Compton) scattering, cause some dose to be delivered to the valley areas adjacent to the microbeams. As the incident x-ray energy is modified, radiation interactions within a material change and affect the probability of interactions, as well as the directionality and energy of ionizing particles (electrons) that deposit energy in the valley regions surrounding the microbeam peaks. It is crucial that the valley dose between microbeams be minimal to maintain the effectiveness of MRT. Using a monochromatic x-ray source with x-ray energies ranging from 30 to 150 keV, a detailed investigation into the effect of incident x-ray energy on the dose profiles of microbeams was performed using samarium doped fluoroaluminate (FA) glass as the medium. All dosimetric measurements were carried out using a purpose-built fluorescence confocal microscope dosimetric technique that used Sm-doped FA glass plates as the irradiated medium. Dose profiles are measured over a very a wide range of x-ray energies at micrometer resolution and dose distribution in the microbeam are mapped. The measured microbeam profiles at different energies are compared with the MCNP6 radiation transport code, a general transport code which can calculate the energy deposition of electrons as they pass through a given material. The experimentally measured distributions can be used to validate the results for electron energy deposition in fluoroaluminate glass. Code validation is necessary for using transport codes in future treatment planning for MRT and other radiation therapies. It is shown that simulated and measured micro beam-profiles are in good agreement, and micrometer level changes can be observed using this high-resolution dosimetry technique. Full width at 10% of the maximum peak (FW@10%) was used to quantify the microbeam width. Experimental measurements on FA glasses and simulations on the dependence of the FW@10% at various energies are in good agreement. Simulations on energy deposited in water indicate that FW@10% reaches a local minimum around energies 140 keV. In addition, variable slit width experiments were carried out at an incident x-ray energy of 100 keV in order to determine the effect of the narrowing slit width on the delivered peak dose. The microbeam width affects the peak dose, which decreases with the width of the microbeam. Experiments suggest that a typical microbeam width for MRT is likely to be between 20-50 µm based on this work.

Evaluation of increased vitamin D fortification in high-temperature, short-time-processed 2% milk, UHT-processed 2% fat chocolate milk, and low-fat strawberry yogurt.

The objective of this study was to determine the effect of increased vitamin D fortification (250 IU/serving) of high-temperature, short-time (HTST)-processed 2% fat milk, UHT-processed 2% fat chocolate milk, and low-fat strawberry yogurt on the sensory characteristics and stability of vitamin D during processing and storage. Three replicates of HTST pasteurized 2% fat milk, UHT pasteurized 2% fat chocolate milk, and low-fat strawberry yogurt were manufactured. Each of the 3 replicates for all products contained a control (no vitamin D fortification), a treatment group with 100 IU vitamin D/serving (current level of vitamin D fortification), and a treatment group with 250 IU vitamin D/serving. A cold-water dispersible vitamin D(3) concentrate was used for all fortifications. The HTST-processed 2% fat milk was stored for 21 d, with vitamin D analysis done before processing and on d 0, 14, and 21. Sensory analysis was conducted on d 14. The UHT-processed 2% fat chocolate milk was stored for 60 d, with vitamin D analysis done before processing and on d 0, 40, and 60. Sensory analysis was conducted on d 40. Low-fat strawberry yogurt was stored for 42 d, with vitamin D analysis done before processing, and on d 0, 28, and 42. Sensory analysis was conducted on d 28. Vitamin D levels in the fortified products were found to be similar to the target levels of fortification (100 and 250 IU vitamin D per serving) for all products, indicating no loss of vitamin D during processing. Vitamin D was also found to be stable over the shelf life of each product. Increasing the fortification of vitamin D from 100 to 250 IU/serving did not result in a change in the sensory characteristics of HTST-processed 2% fat milk, UHT-processed 2% fat chocolate milk, or low-fat strawberry yogurt. These results indicate that it is feasible to increase vitamin D fortification from 100 to 250 IU per serving in these products.

Synergy of gene-mediated immunoprophylaxis and microbeam radiation therapy for advanced intracerebral rat 9L gliosarcomas.

PURPOSE: Microbeam radiation therapy (MRT), a novel experimental radiosurgery that largely spares the developing CNS and other normal tissues, is tolerated well by developing animals and palliates advanced 9LGS tumors. This report, to our knowledge, is the first demonstration that gene-mediated immunotherapy (GMIMPR) enhances the efficacy of MRT for advanced 9LGS tumors. METHODS: Seventy-six male Fischer 344 rats were implanted ic with 10(4)9LGS cells on d0. By d14, the cells had generated approximately approximately 40 mm3 ic 9LGS tumours, experimental models for therapy of moderately aggressive human malignant astrocytomas. Each of the 14 untreated (control) rats died from a large (>100 mg) ic tumor before d29 (median, d21). On d14, the remaining 62 rats were given deliberately suboptimal microbeam radiation therapy (MRT) by a single lateral exposure of the tumor-bearing zone of the head to a 10.1 mm-wide, approximately approximately 11 mm-high array of 20-39 microm-wide, nearly parallel beams of synchrotron wiggler-generated radiation (mainly approximately 50-150 keV X-rays) that delivered 625 Gy peak skin doses at approximately approximately 211 microm ctc intervals in approximately approximately 300 ms either without additional treatments (MRT-only, 25 rats), with post-MRT GMIMPR (MRT+GMIMPR, 23 rats: multiple sc injections of irradiated (clonogenically-disabled) GM-CSF gene-transfected 9LGS cells), or with post-MRT IMPR (MRT+IMPR, 14 rats: multiple sc injections of irradiated (clonogenically-disabled) 9LGS cells. RESULTS: The median post-implantation survivals of rats in the MRT-only, MRT+GMIMPR and MRT+IMPR groups were over twice that of controls; further, approximately approximately 20% of rats in MRT-only and MRT+IMPR groups survived >1 yr with no obvious disabilities. Moreover, over 40% of MRT+GMIMPR rats survived >1 yr with no obvious disabilities, a significant (P<0.04) increase over the MRT-only and MRT+IMPR groups. SIGNIFICANCE: These data suggest that the combination of MRT+GMIMPR might be better than MRT only for unifocal CNS tumors, particularly in infants and young children.

Radiosurgical palliation of aggressive murine SCCVII squamous cell carcinomas using synchrotron-generated X-ray microbeams.

Microbeam radiosurgery (MBRS), also referred to as microbeam radiation therapy (MRT), was tested at the European Synchrotron Radiation Facility (ESRF). The left tibiofibular thigh of a mouse bearing a subcutaneously (sc) implanted mouse model (SCCVII) of aggressive human squamous-cell carcinoma was irradiated in two orthogonal exposures with or without a 16 mm aluminium filter through a multislit collimator (MSC) by arrays of nearly parallel microbeams spaced 200 microm on centre (oc). The peak skin-entrance dose from each exposure was 442 Gy, 625 Gy, or 884 Gy from 35 microm wide beams or 442 Gy from 70 microm wide beams. The 442/35, 625/35, 884/35 and 442/70 MBRSs yielded 25 day, 29 day, 37 day and 35 day median survival times (MST) (post-irradiation), respectively, exceeding the 20 day MST from 35 Gy-irradiation of SCCVIIs with a seamless 100 kVp X-ray beam.

Remifentanil sedation compared with propofol during regional anaesthesia.

BACKGROUND: The short onset and offset of remifentanil may allow for accurate dosing of sedative effect with few side-effects and rapid recovery. In this study remifentanil is compared with propofol for sedation during successful regional anaesthetic blocks. METHODS: After informed consent was given, 125 patients undergoing surgery under spinal or brachial plexus anaesthesia were randomized to receive, either propofol: bolus 500 microg/kg plus initial infusion 50 microgkg/min or remifentanil: bolus 0.5 microg/kg plus initial infusion 0.1 microgkg/min. Study drug infusion rate was titrated throughout the procedure according to level of sedation and side-effects. Pain, discomfort, sedation level and side-effects were recorded at regular intervals until discharge from the post operative care unit (PACU). RESULTS: Two patients in the remifentanil group versus ten in the propofol group were treated for discomfort or pain during surgery (P<0.02). Due to a significantly higher rate of respiratory depression (46% vs. 19% with propofol, P<0.01) the mean remifentanil infusion rate was decreased to 0.078 +/- 0.028 microgkg/min, whereas it was kept stable with propofol. Propofol patients had significantly higher (P<0.05) sedation levels and experienced more frequent amnesia of the procedure. Eleven propofol patients experienced pain at injection site, versus two remifentanil patients (P<0.02). Nausea and vomiting were more frequent in the remifentanil patients during infusion (27% vs. 2% in the propofol group, P<0.001) but similar postoperatively. Time to discharge from PACU was similar in the two groups. CONCLUSION: Propofol results in less respiratory depression and nausea when sedation is needed during a case with a successful regional block. Remifentanil may be considered as an alternative if pain during the procedure is a major concern or if amnesia is contraindicated.

Psychiatric care for patients with HIV infection. The varying perspectives.

This article reviews the literature on the classification and treatment of psychiatric morbidity associated with infection from the human immunodeficiency virus (HIV). The psychiatric disorders seen in HIV-infected patients are formulated by using one of the following four perspectives as treatment guides: 1) the syndromal or disease perspective, 2) the dispositional or personality perspective, 3) the behavioral or addictive perspective, and 4) the life story perspective.

Manic syndrome early and late in the course of HIV.

In a chart review at a hospital's infectious disease AIDS clinic, manic syndromes affected 8% of patients who had AIDS. Of the 14 patients with manic episodes, those without a family or personal history of mood disorder presented later in the course of HIV infection and had a higher prevalence of comorbid dementia.

Tracking the clinical psychiatric literature : what is out there?

This paper reviews the various resources available to psychiatrists for keeping abreast of the current literature and research in the field and reports the results of a survey that assesses psychiatrists' current practices in tracking the literature. The respondents' knowledge of available resources, their usual searching practices, and their satisfaction with the resource network are presented. The authors draw conclusions about the most efficient means of tracking the literature for various purposes and offer suggestions about improving resources.

An X-ray microprobe facility using synchrotron radiation.

An X-ray microprobe for trace elemental analysis at micrometer spatial resolutions, using synchrotron radiation (SR), is under development. The facility consists of two beamlines, one including a 1:1 focusing mirror and the other an 8:1 ellipsoidal mirror. At present, "white light" is used for excitation of the characteristic X-ray fluorescence lines. Sensitivities in thin biological samples are in the range of 2-20 fg in 100 microns2 areas in 5 min irradiation times. Scanning techniques, as well as microtomography and chemical speciation, are discussed. Application to a specific biomedical study is included.

X-ray fluorescence with synchrotron radiation.

The use of synchrotron radiation for X-ray fluorescence has several advantages over the use of other conventional X-ray sources. The principles of synchrotron radiation and methods for applying synchrotron radiation to the X-ray fluorescence measurements of trace elements are discussed. The Brookhaven National Laboratory X-ray microprobe, facilities dedicated to X-ray fluorescence, and related analytical techniques are discussed. Some examples of trace element analyses in biological materials with synchrotron radiation are presented.

Educating today's students to practice pharmacy in the 21st century: reaction from the perspective of continuing education.

In summary, I have described changes which will occur within continuing education to better prepare the pharmacy school graduate to practice in the 21st century. One level of change deals with an attitude toward lifelong learning which in turn affects the efficiency of continuing education. Although some effort to address this issue currently takes place at the undergraduate level, students in the coming years will witness an increased effort recognizing the importance of lifelong learning with appropriate sensitization and nurturing of self-directed study skills to assist in the lifelong learning process. The second level of change focuses on sophistication within CE and involves a significant change, at least by some providers, in program content which will be more rigorous and tailor-made in the needs of individual practitioners. Through increased efficiency and sophistication, continuing education will be perceived differently in the 21st century. Rather than a current view of continuing education as one of many types of postgraduate education and training, continuing education will be viewed as a learning process which encompasses or includes all other types of postgraduate education and training.

Effect of use-criteria for intravenous administration sets.

Numbers of intravenous administration sets used were studied in a 480-bed hospital before and after criteria for selecting sets were implemented. Criteria for use of eight common administration sets were developed by a committee of nurses and pharmacists. Hospital drug-use review was used as a pattern. Baseline data were collected for seven-day periods on each of five patient-care units; twice daily, one pharmacist recorded the numbers of sets used and determined their compliance with the criteria, which had been established but not disseminated to nurses or implemented. After nurses were instructed on use of the criteria, data were collected for a second seven-day period on each unit. Use of each set type as a percentage of all sets and compliant use of each type as a percentage of all compliant use were calculated. Annual hospitalwide cost savings were predicted from the observed changes in use and the hospital's costs in the six-month period before the study. Significant changes occurred in overall use and in use of individual set types. For each set type, use compliant with the criteria increased. Notable changes included decreased use of volumetric chambers (burettes) and increased relative use of Y maxidrip and Y minidrip sets. Annual savings of more than +20,000 were predicted. Criteria for selection of i.v. administration sets had an effect on set use at this hospital.

The need for evaluation of the ultimate impact of continuing pharmaceutical education.

Many governmental agencies and professional associations are using continuing education as the single, and relatively untested, means of ensuring that professionals maintain an acceptable level of knowledge and skills. The ultimate goal of continuing education in the health professions is improved professional performance leading to an improvement in the quality of health care provided. However, there is justifiable concern over the lack of a significant link between participation in continuing education activities and professional competence. This issue is explored and a conceptual framework for the evaluation of continuing pharmaceutical education is presented. The conceptual framework is an evaluation hierarchy which depicts the following four levels of a comprehensive evaluation process: participant satisfaction; changes in knowledge, attitudes, and skills; behavior change in practice setting; and improvement in patient care.

Regional distribution of lead in the brains of lead-intoxicated adult mice.

The susceptibility of adult neural tissues to the detrimental effects of Pb poisoning has prompted the present distributional analysis of lead in the brains of chronically lead-exposed mice. A high-resolution microPIXE method was developed for measuring Pb in whole-brain cryosections derived from chronically lead-exposed mice. Spatial resolutions as small as 20 micron were obtained. Details of the methodology are presented together with procedures for Pb standard preparation and control measures employed to reduce potential errors of Pb assay associated with taking brain sections with steel alloy knives. The unique advantages of making microPIXE Pb determinations in nonpreselected brain anatomic regions using freeze-dried semithick cryosections are reviewed. The study revealed that, in lead-intoxicated mice, there existed wide regional variation in Pb concentration in the ppm range, in 50 micron sagittal or coronal sections. Higher Pb levels were found in discrete brain regions of lead-treated adult mice than in matched control brains. Suggestions for further studies of Pb kinetics using microPIXE methods in adults and immature animals, including components of neural barrier tissues, are reviewed.

Epidural anesthesia for cesarean section. The effect of morphine-bupivacaine administered epidurally for intra and postoperative pain relief.

Two groups of mothers who underwent elective cesarean section under epidural analgesia, were studied with the aim of comparing the analgesic potency and side effects of two solutions: morphine-bupivacaine and morphine-saline. Each group comprised 100 patients. The intraoperative anesthesia was established with bupivacaine plain, 5 mg/ml, in amount 85-125 mg. Immediately after the infant was delivered, the mothers received a single epidural dose of 3 mg of preservative-free morphine chloride mixed with either 5 ml of 0.25% bupivacaine (Group I) or 0.9% saline (Group II). The intraoperative observations showed "good effect" without need for supplementation of analgesia in 82 mothers in Group I, compared with 61 mothers in Group II (p less than 0.001). The postoperative observations showed that 82 mothers in Group I were satisfied with a single dose of morphine for more than 24 hours, while in Group II the corresponding number was 63 (p less than 0.01). A significant difference in the incidence of nausea and vomiting was found between the groups; 7 of the mothers experienced nausea and 4 vomited in Group I and 17 experienced nausea and 13 vomited in Group II (p less than 0.05, for both variables). Respiratory depression was seen in one mother during surgery immediately after supplementation of morphine-bupivacaine analgesia with ketamine. Other side effects, such as itching, bradycardia and Horner's triad were rare. It may be concluded that a single epidural dose of morphine in bupivacaine will augment intraoperative analgesia and prolong postoperative analgesia. Less favorable results were obtained when morphine in saline was used. Synergism between bupivacaine and morphine is suggested.

Mercury toxicity and dental amalgam.

There is adequate evidence that dental amalgam restorations, during and after placement, results in the release of Hg into the patient's body. Whether the Hg released from amalgam is due to placement procedures, surface abrasion, or later corrosion breakdown, there is evidence that a low level Hg release continues for years. It is generally agreed that if amalgam was introduced today as a restorative material, they would never pass F.D.A. approval. With new and more accurate techniques of measuring Hg levels, especially in tissue and blood, additional studies are necessary to relate blood-Hg levels with dental amalgam restorations. Studies must relate existing restorations as well as the placement of new restorations to body-Hg levels. It is possible that we have accepted a potentially dangerous material as being safe.

Juvenile rickets and hyperparathyroidism in the Arctic fox.

Three of seven Arctic fox kits, Alopex lagopus, trapped on St. Paul Island, Alaska, had evidence of rickets and hyperparathyroidism. Radiographic, morphologic and histologic examination confirmed the diagnosis. The disease was presumed to be a juvenile-onset disease due to calcium-deficient intake following weaning. The possibility of insufficient exposure to sunlight could not be determined. No other abnormalities (e.g., genitourinary) were found. Skeletal involvement was quite varied. All growth plates exhibited columnar hyperplasia compatible with rickets, while the metaphyses showed decreased trabeculation and cortical thinning compatible with osteodystrophia fibrosa. One fox had bilateral metaphyseal fractures through this osteodystrophic bone.