Investigating the air kerma rate constant for 241Am through first principle calculations and simulation.

The air kerma rate constant is important for estimating radiation dose and shielding calculations to ensure radiation exposure is as low as reasonably achievable (ALARA). Currently, there are significant deviations in this constant reported for 241Am by various institutions. Therefore, through first principle calculations and simulation, we investigate the air kerma rate constant for 241Am based on photon energies and emission probabilities reported in literature.

Investigating coherent normalization and dosimetry for the 241Am-La K XRF system.

OBJECTIVES: Lanthanum (La) retention in bone has been shown to occur in individuals who are orally administered lanthanum carbonate (LaC), a drug to treat hyperphosphatemia. The breakdown of LaC in the gastrointestinal tract into La3+ and carbonate ions results in residual quantities of La being deposited in bone. We previously reported on a non-invasive x-ray fluorescence (XRF) system that was developed to quantify bone La concentrations and applied it to a series of excised cadaver tibiae. However, given interpatient variability in bone shape and size, differential signal attenuation that occurs in bone and tissue, patient movement and overlying tissue thickness at the measurement site, quantifying bone La concentrations during in vivo measurements in live subjects needs to be investigated further along with the radiation dose associated with the measurement. APPROACH: Coherent normalization was investigated as a function of overlying tissue thickness, source-subject distance and bone radius through Monte Carlo simulation and experimental work. This was accomplished by observing the ratio of the net La K x-ray peak area to the coherently scattered peak area at 59.5 keV. In addition, the dose delivered during a 2000 s measurement was determined using radiochromic film. MAIN RESULTS: The coherent normalization of the La x-ray signal was shown to be independent of overlying tissue thickness, source-subject movement and bone radius, which indicates that this normalization procedure can correct for these factors. The equivalent skin dose and effective dose were 18.0 mSv and 3.2 µSv, respectively for a five-year-old. SIGNIFICANCE: While coherent normalization for the bone lead (Pb) and bone gadolinium (Gd) systems has been shown to be successful, we also report that this normalization procedure can correct for these interpatient variabilities in the in vivo 241Am-La K XRF system.

Ex vivo quantification of lanthanum and gadolinium in post-mortem human tibiae with estimated barium and iodine concentrations using K x-ray fluorescence.

OBJECTIVES: Lanthanum (La) and gadolinium (Gd) are known to deposit in bone of exposed populations, namely those who are orally administered lanthanum carbonate (LaC, La2(CO3)3) or are injected with Gd-based contrast agents, respectively. In this work, bone La and Gd concentrations from the environment and diet were measured using x-ray fluorescence in ten post-mortem human tibiae. As a secondary objective, bone barium (Ba) and iodine concentrations were estimated. APPROACH: Two calibration lines were produced for La and Gd and the minimum detection limits (MDLs) of the system were determined using a 180° irradiation-detection geometry. MAIN RESULTS: The MDLs of the system were 0.4 µg La g-1 bone mineral and 0.5 µg Gd g-1 bone mineral. The mean concentrations were -0.02 ± 0.1 µg La g-1 bone mineral and 0.1 ± 0.2 µg Gd g-1 bone mineral in tibiae. The average Ba and iodine concentrations estimated from the experimental La calibration line and Monte-Carlo derived sensitivity factors were determined to be 3.4 ± 0.8 µg Ba g-1 bone mineral and -0.5 ± 0.3 µg iodine g-1 bone mineral. Since it was discovered that four donors previously received an iodine-based contrast agent, the mean concentrations in these donors was 27.8 ± 28.4 µg iodine g-1 bone mineral. SIGNIFICANCE: The XRF system has determined baseline concentrations of these four heavy metals in trace quantities from natural exposure pathways (with the exception of iodine in four donors). This indicates that the system can measure low levels in ex vivo tibiae samples and can potentially be further developed for in vivo studies involving live subjects who are directly exposed to these metals.

The feasibility of in vivo detection of lanthanum using a 241Am K x-ray fluorescence system.

OBJECTIVE: Lanthanum (La) is commonly used in phosphate binders in the form of lanthanum carbonate in patients with end-stage kidney disease undergoing hemodialysis treatments. With this administration, there is the potential for La storage in the body with bone being the main site of concern. However, the long-term effects of residual La in the body on bone health are not yet known. In this work, we investigate the feasibility of using a K x-ray fluorescence (K-XRF) spectroscopy system to measure bone La in vivo. APPROACH: A series of hydroxyapatite (HAp) bone mineral phantoms were created to represent human bone. A 1.09 GBq 241Am source was used to excite the HAp phantoms doped with various known concentrations of La placed in a 90° geometry relative to the photon source and high-purity germanium (HPGe) detector. MAIN RESULTS: For a detector live time of 2000 s, the minimum detection limit was calculated to be 1.7 µg La g-1 Ca or 0.7 µg La g-1 HAp and is comparable to previously reported in vivo bone La concentrations. SIGNIFICANCE: The technique developed in this study shows promising results and provides an alternative method to invasive biopsy sampling techniques to monitor the accumulation of bone La. To the best of our knowledge, this is the first reported work that seeks to non-invasively measure bone La via in vivo XRF.

A Comparative Analysis of Recombinant Human Bone Morphogenetic Protein-2 with a Demineralized Bone Matrix versus Iliac Crest Bone Graft for Secondary Alveolar Bone Grafts in Patients with Cleft Lip and Palate: Review of 501 Cases.

BACKGROUND: Alveolar cleft reconstruction using iliac crest bone graft is considered standard of care for children with complete cleft lip and palate at the time of mixed dentition. Harvesting bone may result in donor-site morbidity and additional operating time and length of hospitalization. Recombinant human bone morphogenetic protein (rhBMP)-2 with a demineralized bone matrix is an alternative bone source for alveolar cleft reconstruction. The authors investigated the outcomes of rhBMP-2/demineralized bone matrix versus iliac crest bone graft for alveolar cleft reconstruction by reviewing postoperative surgical complications and cleft closure. METHODS: A retrospective chart review was conducted for 258 rhBMP-2/demineralized bone matrix procedures (mean follow-up, 2.9 years) and 243 iliac crest bone graft procedures (mean follow-up, 4.1 years) on 414 patients over a 12-year period. The authors compared complications, canine eruption, and alveolar cleft closure between the two groups. RESULTS: In the rhBMP-2/demineralized bone matrix group, one patient required prolonged intubation because of intraoperative airway swelling not thought to be caused by rhBMP-2, 36 reported facial swelling and one required outpatient steroids as treatment, and 12 had dehiscence; however, half of these complications resolved without intervention. Twenty-three of the 228 rhBMP-2/demineralized bone matrix patients and 28 of the 242 iliac crest bone graft patients required repeated surgery for alveolar cleft repair. Findings for canine tooth eruption into the cleft site through the graft were similar between the groups. CONCLUSIONS: The rhBMP-2/demineralized bone matrix appears to be an acceptable alternative for alveolar cleft repair. The authors found no increase in serious adverse events with the use of this material. Local complications, such as swelling and minor wound dehiscence, predominantly improved without intervention. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Microsurgical Lower Extremity Reconstruction in the Subacute Period: A Safe Alternative.

BACKGROUND: Microsurgical reconstruction of the lower extremity is an integral part of the limb salvage algorithm. Success is defined by a pain-free functional extremity, with a healed fracture and sufficient durable soft tissue coverage. Although early flap coverage of lower extremity fractures is an important goal, it is not always feasible because of multiple factors. Between the years 2000 and 2010, approximately 50% of patients at Los Angeles County and University of Southern California Medical Center requiring microsurgical reconstruction did not receive soft tissue coverage until more than 15 days postinjury secondary to primary trauma, physiologic instability, patient comorbidities, or orthopedic and plastic surgery operative backlog. The objective of our study was to evaluate outcomes in patients who underwent microsurgical reconstruction of the lower extremity, in relation to the timing of reconstruction. METHODS: A retrospective chart review was performed for patients requiring immediate lower extremity reconstruction from January 2000 to December 2009 at LAC + USC. RESULTS: Fifty-one patients were identified in this study. The most common mechanisms of injury were motorcycle, motor vehicle, and fall accidents. Eighty-six percent of injuries were open and 74% were comminuted. The distal 1/3 of the tibia, including the tibial pilon, was the most common location of injury. When comparing patients reconstructed in less than 15 days versus greater than or equal to 15 days, there was no significant difference in rates of flap failure, osteomyelitis, bony union, or ambulation. CONCLUSION: Microsurgical reconstruction of the lower extremity in the subacute period is a safe alternative.

Defective fast inactivation recovery of Nav 1.4 in congenital myasthenic syndrome.

OBJECTIVE: To describe the unique phenotype and genetic findings in a 57-year-old female with a rare form of congenital myasthenic syndrome (CMS) associated with longstanding muscle fatigability, and to investigate the underlying pathophysiology. METHODS: We used whole-cell voltage clamping to compare the biophysical parameters of wild-type and Arg1457His-mutant Nav 1.4. RESULTS: Clinical and neurophysiological evaluation revealed features consistent with CMS. Sequencing of candidate genes indicated no abnormalities. However, analysis of SCN4A, the gene encoding the skeletal muscle sodium channel Nav 1.4, revealed a homozygous mutation predicting an arginine-to-histidine substitution at position 1457 (Arg1457His), which maps to the channel's voltage sensor, specifically D4/S4. Whole-cell patch clamp studies revealed that the mutant required longer hyperpolarization to recover from fast inactivation, which produced a profound use-dependent current attenuation not seen in the wild type. The mutant channel also had a marked hyperpolarizing shift in its voltage dependence of inactivation as well as slowed inactivation kinetics. INTERPRETATION: We conclude that Arg1457His compromises muscle fiber excitability. The mutant fast-inactivates with significantly less depolarization, and it recovers only after extended hyperpolarization. The resulting enhancement in its use dependence reduces channel availability, which explains the patient's muscle fatigability. Arg1457His offers molecular insight into a rare form of CMS precipitated by sodium channel inactivation defects. Given this channel's involvement in other muscle disorders such as paramyotonia congenita and hyperkalemic periodic paralysis, our study exemplifies how variations within the same gene can give rise to multiple distinct dysfunctions and phenotypes, revealing residues important in basic channel function.

COOH-terminal collagen Q (COLQ) mutants causing human deficiency of endplate acetylcholinesterase impair the interaction of ColQ with proteins of the basal lamina.

Collagen Q (ColQ) is a key multidomain functional protein of the neuromuscular junction (NMJ), crucial for anchoring acetylcholinesterase (AChE) to the basal lamina (BL) and accumulating AChE at the NMJ. The attachment of AChE to the BL is primarily accomplished by the binding of the ColQ collagen domain to the heparan sulfate proteoglycan perlecan and the COOH-terminus to the muscle-specific receptor tyrosine kinase (MuSK), which in turn plays a fundamental role in the development and maintenance of the NMJ. Yet, the precise mechanism by which ColQ anchors AChE at the NMJ remains unknown. We identified five novel mutations at the COOH-terminus of ColQ in seven patients from five families affected with endplate (EP) AChE deficiency. We found that the mutations do not affect the assembly of ColQ with AChE to form asymmetric forms of AChE or impair the interaction of ColQ with perlecan. By contrast, all mutations impair in varied degree the interaction of ColQ with MuSK as well as basement membrane extract (BME) that have no detectable MuSK. Our data confirm that the interaction of ColQ to perlecan and MuSK is crucial for anchoring AChE to the NMJ. In addition, the identified COOH-terminal mutants not only reduce the interaction of ColQ with MuSK, but also diminish the interaction of ColQ with BME. These findings suggest that the impaired attachment of COOH-terminal mutants causing EP AChE deficiency is in part independent of MuSK, and that the COOH-terminus of ColQ may interact with other proteins at the BL.

Pfeiffer syndrome twins: despite improved correction in one twin, growth disturbance results in similar need for subsequent monobloc advancement.

BACKGROUND: Twins with Pfeiffer syndrome (or acrocephalosyndactyly) had a similar phenotypic appearance with findings of classic or type 1 Pfeiffer syndrome, including bicoronal and sagittal craniosynostoses, midface hypoplasia, and broad thumbs/toes. We document their treatment with 2 monobloc advancements and discuss growth disturbances in craniofacial dysostosis. METHODS: At 6 months, both twins underwent release of multisuture (bilateral coronal and sagittal) fusions for improvement of scaphocephalic shape and multisuture release; however, one twin had a more aggressive procedure with advancement of the frontal-orbital region. Despite improved initial correction by one twin, at 5 years of age, both twins presented with midface hypoplasia and exorbitism and underwent a monobloc distraction procedure with similar 20-mm advancements. Comparative analysis by our craniofacial multidisciplinary team included perioperative reports, computed tomographic scans, cephalograms, parent questionnaires, and physician surveys. RESULTS: Both twins had an improved confidence interval scores from 84 to 68 and 82 to 69 postoperatively. In 6-month follow-up, the Whitaker score of the first twin was 2.8, whereas that for the second twin with the frontal-orbital advancement was 1.2. Preschool expressive and receptive tests yielded 97 and 95, and 97 and 98, and developmental testing was similar between the twins. Global evaluations were equivalent to age-matched controls, and memory and attention skills were within normal limits. Parental surveys showed a high level of satisfaction after all procedures in both twins. CONCLUSIONS: Our study demonstrates that the phenotypic outcome for both twins remained unchanged when comparing a more aggressive surgery to less aggressive surgery as an infant. The genetic mutation may have overridden the different surgical interventions. Both twins ultimately required 2 subsequent monobloc corrections.

Roman arch, keystone fixation for facial bipartition with monobloc distraction.

BACKGROUND: Patients with craniofacial dysostosis may require correction for hypertelorbitism and midface hypoplasia. Traditionally, these procedures were sequential or staged, and used acute advancement with bone grafting and rigid fixation. The authors reviewed a series of combined, one-stage facial bipartition and monobloc distraction procedures using internal devices. They describe the Roman arch, keystone fixation modification to maximize the stability of the bipartition segments and support the vertical load of the distraction forces. METHODS: Patients diagnosed at the University of California, Los Angeles as having craniofacial dysostosis with hypertelorbitism and midface hypoplasia who underwent the Roman arch, keystone fixation procedure were included in the study (n = 13). Reduction of interdacryon and intercanthal distances and the lateral cephalometric horizontal change of the forehead, midface, and maxilla were studied postoperatively and at 1-year follow-up. RESULTS: There were no serious complications (e.g., cerebrospinal fluid leak, meningitis, frontal bone loss); there was a 10 percent rate of total complications (wound infection). Facial bipartition successfully narrowed the interdacryon distance by a mean of 55 percent (21 mm), with only a 3-mm relapse. The mean distraction advancement/relapse was as follows: forehead, +16 mm/-2 mm; midface, 14 mm/-1 mm; and maxilla, 13 mm/-1 mm. Only one of 13 patients required a repeated monobloc procedure. Of the seven patients who reached skeletal maturity, 86 percent underwent a subsequent Le Fort I and/or III procedure. CONCLUSION: The Roman arch, keystone fixation modification of a combined facial bipartition with monobloc distraction using internal devices provided a stable construct for advancement, with minimal relapse.