Radiation Safety Aspects of Iodine-131 metaiodobenzylguanidine (131I mIBG) Therapy Program Startup.

As a medical center without a pre-existing radiopharmaceutical therapy program, it was a daunting endeavor to implement a I metaiodobenzylguanidine (mIBG) high-dose treatment regimen. It took several years of planning with hospital administration, vendors, and Texas Department of Health Radiological Control regulators to establish a viable program. Effective communication between physicians, nursing, nuclear medicine, environmental services, maintenance, and other support staff is essential and paramount for the successful execution and continued sustainability of the mIBG therapy program. Besides providing an effective treatment for patients, an additional goal for the program is to keep radiation exposure As Low As Reasonably Achievable (ALARA) for staff and patient caregivers. As such, start-up presented many training, logistical, and radiation safety challenges. The location of the isolation room and shielding specifications were designed to keep radiation exposure to public access areas to less than 2 microsieverts per hour. Before the first patient was treated the policies and procedures for training, radiation safety, product quality control, and infusion process needed to be developed, tested, and approved by various committees. Furthermore, a similar process was required for developing room set-up, post therapy cleanup, and waste storage procedures. Throughout the maturation process of the program, the departments involved have found that our safety culture has continually improved by the re-enforcement of knowledge and lessons learned, as both the ancillary and treatment staff grew more confident in each other's ability during more patient treatments are performed. This article describes the process and lessons learned during the time leading up to the startup and early years of the mIBG therapy program.

Validation of the composite autonomic symptom scale 31 (COMPASS-31) in patients with and without small fiber polyneuropathy.

BACKGROUND AND PURPOSE: The recently developed composite autonomic symptom score 31 (COMPASS-31) is a questionnaire that assess symptoms of dysautonomia. It was distilled from the well-established Autonomic Symptom Profile questionnaire. COMPASS-31 has not yet been externally validated. To do so, its psychometric properties and convergent validity in patients with and without objective diagnosis of small fiber polyneuropathy (SFPN) were assessed. METHODS: Internal validity and reliability of COMPASS-31 were assessed in participants with or without SFPN spanning the full range of severity of autonomic symptoms. Convergent validity was assessed by comparing results of the COMPASS-31 with the "gold standard" autonomic function testing that measures cardiovagal, adrenergic and sudomotor functions. Additionally, relationships between COMPASS-31 and the Short Form McGill Pain Questionnaire, Short Form Health Survey and 0-10 numeric pain scale were measured. COMPASS-31 and all other questionnaire results were compared between patients with or without evidence of SFPN, objectively confirmed by distal-leg PGP9.5-immunolabeled skin biopsy. RESULTS: Amongst 66 participants (28 SFPN+, 38 SFPN-), COMPASS-31 total scores had excellent internal validity (Cronbach's α = 0.919), test-retest reliability (r(s) = 0.886; P < 0.001) and good convergent validity (r(s) = 0.474; P < 0.001). COMPASS-31 scores differed between subjects with or without SFPN (Z = -3.296, P < 0.001) and demonstrated fair diagnostic accuracy. Area under the Receiver Operating Characteristic curve was 0.749 (P = 0.01, 95% confidence interval 0.627-0.871). CONCLUSIONS: COMPASS-31 has good psychometric properties in the population of patients being evaluated for SFPN and thus it might be useful as an initial screening tool for the more expensive SFPN objective tests.

Endoneurial pathology of the needlestick-nerve-injury model of Complex Regional Pain Syndrome, including rats with and without pain behaviors.

Current rodent models of neuropathic pain produce pain hypersensitivity in almost all lesioned animals and not all identified experimental effects are pain specific. 18G needlestick-nerve-injury (NNI) to one tibial nerve of outbred Sprague-Dawley rats models the phenotype of Complex Regional Pain Syndrome (CRPS), a post-traumatic neuropathic pain syndrome, leaving roughly half of NNI rats with hyperalgesia. We compared endoneurial data from these divergent endophenotypes searching for pathological changes specifically associated with pain-behaviors. Tibial, sural, and common sciatic nerves from 12 NNI rats plus 10 nerves from sham-operated controls were removed 14 days post-surgery for morphometric analysis. PGP9.5(+) unmyelinated-fibers were quantitated in plantar hindpaw skin. Distal tibial nerves of NNI rats had endoneurial edema, 30% fewer axons, twice as many mast cells, and thicker blood-vessel walls than uninjured tibial nerves. However the only significant difference between nerves from hyperalgesic versus non-hyperalgesic NNI rats was greater endoneurial edema in hyperalgesic rats (p < 0.01). We also discovered significant axonal losses in uninjured ipsilateral sural nerves of NNI rats, demonstrating spread of neuropathy to nearby nerves formerly thought spared. Tibial and sural nerves contralateral to NNI had significant changes in endoneurial blood-vessels. Similar pathological changes have been identified in CRPS-I patients. The current findings suggest that severity of endoneurial vasculopathy and inflammation may correlate better with neuropathic pain behaviors than degree of axonal loss. Spread of pathological changes to nearby ipsilateral and contralateral nerves might potentially contribute to extraterritorial pain in CRPS.

Cognition, sleep and respiration in at-risk children treated for obstructive sleep apnoea.

Sleep-disordered breathing in children has been associated with cognitive impairment. The purpose of this study was to examine the impact of tonsillectomy and adenoidectomy (T&A) on sleep, respiration and cognitive function in children of pre-school age with obstructive sleep apnoea (OSA) from a low-income community population. Altogether, 19 children attending state-funded pre-school programmes underwent overnight polysomnography and cognitive assessment before and following surgical treatment for OSA; 19 matched controls were also assessed. Following T&A, OSA subjects' delta sleep increased, rapid eye movement sleep decreased, and respiratory and arousal indices improved. There were no significant differences in OSA subjects' post-operative sleep or respiratory measures compared to controls. Prior to T&A, cognitive scores were significantly lower in OSA subjects versus controls; following T&A, OSA subjects' scores improved compared to pre-operative scores and did not differ from those of matched controls. Following tonsillectomy and adenoidectomy, at-risk pre-schoolers recruited directly from the community showed normalised sleep and respiratory patterns and improved cognitive scores. These findings, in this uniquely vulnerable population, which is unlikely to seek evaluation and treatment for obstructive sleep apnoea, underscore the potential value of outreach screening programmes for sleep-disordered breathing, particularly among low-income groups of pre-school age.

Global spatial normalization of human brain using convex hulls.

UNLABELLED: Global spatial normalization transforms a brain image so that its principal global spatial features (position, orientation and dimensions) match those of a standard or atlas brain, supporting consistent analysis and referencing of brain locations. The convex hull (CH), derived from the brain's surface, was selected as the basis for automating and standardizing global spatial normalization. The accuracy and precision of CH global spatial normalization of PET and MR brain images were evaluated in normal human subjects. METHODS: Software was developed to extract CHs of brain surfaces from tomographic brain images. Pelizzari's hat-to-head least-square-error surface-fitting method was modified to fit individual CHs (hats) to a template CH (head) and calculate a nine-parameter coordinate transformation to perform spatial normalization. A template CH was refined using MR images from 12 subjects to optimize global spatial feature conformance to the 1988 Talairach Atlas brain. The template was tested in 12 additional subjects. Three major performance characteristics were evaluated: (a) quality of spatial normalization with anatomical MR images, (b) optimal threshold for PET and (c) quality of spatial normalization for functional PET images. RESULTS: As a surface model of the human brain, the CH was shown to be highly consistent across subjects and imaging modalities. In MR images (n = 24), mean errors for anterior and posterior commissures generally were <1 mm, with SDs < 1.5 mm. Mean brain-dimension errors generally were <1.3 mm, and bounding limits were within 1-2 mm of the Talairach Atlas values. The optimal threshold for defining brain boundaries in both 18F-fluorodeoxyglucose (n = 8) and 15O-water (n = 12) PET images was 40% of the brain maximum value. The accuracy of global spatial normalization of PET images was shown to be similar to that of MR images. CONCLUSION: The global features of CH-spatially normalized brain images (position, orientation and size) were consistently transformed to match the Talairach Atlas in both MR and PET images. The CH method supports intermodality and intersubject global spatial normalization of tomographic brain images.

Biological and behavioral correlates of quiet sleep respiration rates in infants.

The sleep and respiration of 88 infants were recorded for 24-h periods on the first 2 postnatal days and again at 6 months. The recordings were made with the Motility Monitoring System, which does not require instrumentation of the infants. Quiet sleep respiration rates (QSRR) increased over the first 2 days (mean = 42.2, SD = 1.0 and mean = 44.5, SD = 1.1, respectively), then decreased by 6 months (mean = 25.3, SD = 0.5); females showed lower QSRR on the first 2 days, infants delivered vaginally showed lower QSRR at 6 months; by 6 months QSRR was significantly higher during the day than at night; and significant individual differences across age and from day to nighttime were found at each age. Delivery mode, maternal age and education, and mental scores at 6 and 12 months were negatively related to QSRR at 6 months. Taken together, these data suggest a developmental advantage of slower QSRR and evidence for the role of the higher central nervous centers in the regulation of QSRR.

Inference for an age-dependent, multitype branching-process model of mast cells.

We consider an age-dependent, multitype model for the growth of mast cells in culture. After a colony of cells is established by an initiator type, the two possible types of cells are resting and proliferative. Using novel inferential procedures, we estimate the generation-time distribution and the offspring distribution of proliferative cells, and the waiting-time distribution of resting cells.

A stochastic model for mast cell proliferation in culture.

A birth-death model was developed for the proliferation of mast cells. According to the model, each secondary mast cell colony starts with one proliferative cell. At each generation each cell chooses among three possibilities: 1) division into two proliferative cells; 2) division into two non-proliferative cells; or 3) disappearance. At each step, a non-proliferative cell either does nothing or disappears. A computer simulation of this model could be fitted reasonably well to our data for the size distributions of secondary mast cell colonies recorded after different culture periods. Our model predicts that proliferative cells comprise a larger fraction of the colony in large secondary colonies than in small ones. This prediction was successfully tested by examination of tertiary colony formation. This is a general model for cell proliferation that may be applicable to other types of cells.

Epidemic measles in a highly vaccinated population.

During November, 1975, to May, 1976, measles occurred at a rate of 20.3 cases per 1000 in a purported immunized population, of whom historical and serologic survey revealed that 9 per cent had no history of either measles illness or vaccination and 18 per cent did not have detectable measles antibody. Antibody was detectable in 92 per cent of those vaccinated at greater than or equal to 13 months, 80 per cent at 12 months and 67 per cent of those vaccinated when less than one year old (P less than 0.001), but no significant differences existed with increasing years since vaccination (P greater than 0.1). A second vaccination increased detectable antibody prevalence only in those originally vaccinated when less than nine months old (42 to 80 per cent, P less than 0.02). During a measles outbreak, more cases occurred in those receiving vaccine when less than 12 months old than in those vaccinated at greater than or equal to 12 months (37 per cent vs. 9 per cent, P less than 0.001). A second vaccination protected those originally vaccinated at less than 12 months (35 per cent ill without a second vaccination vs. 2 per cent with, P less than 0.001). Thus, a single measles vaccination of children less than 12 months old does not protect; a second vaccination will protect this group.