Accelerator mass spectrometry at Arizona: geochronology of the climate record and connections with the ocean.

There are many diverse uses of accelerator mass spectrometry (AMS). Carbon-14 studies at our laboratory include much research related to paleoclimate, both with 14C as a tracer of past changes in environmental conditions as observed in corals, marine sediments and many terrestrial records. Terrestrial records such as forest fires can also show the influence of oceanic oscillations, whether they are short-term such as ENSO, or on the millennial time scale. In tracer applications, we have developed the use of 129I as well as 14C as tracers for nuclear pollution studies around radioactive waste dump sites, in collaboration with IAEA. We discuss some applications carried out in Tucson for several of these fields and hope to give some idea of the breadth of these studies.

Accelerator mass spectrometry at Arizona: geochronology of the climatic record and connections with the ocean.

There are many diverse uses of accelerator mass spectrometry (AMS). 14C studies at our laboratory include much research related to paleoclimate, with 14C as a tracer of past changes in environmental conditions as observed in corals, marine sediments, and many terrestrial records. Terrestrial records can also show the influence of oceanic oscillations, whether they are short term, such as ENSO (El Niño/Southern Oscillation), or on the millennial time scale. In tracer applications, we have developed the use of 129I as well as 14C as tracers for nuclear pollution studies around radioactive waste dump sites, in collaboration with IAEA. We discuss some applications carried out in Tucson, AZ, for several of these fields and hope to give some idea of the breadth of these studies.

Extremely large variations of atmospheric 14C concentration during the last glacial period.

A long record of atmospheric 14C concentration, from 45 to 11 thousand years ago (ka), was obtained from a stalagmite with thermal-ionization mass-spectrometric 230Th and accelerator mass-spectrometric 14C measurements. This record reveals highly elevated Delta14C between 45 and 33 ka, portions of which may correlate with peaks in cosmogenic 36Cl and 10Be isotopes observed in polar ice cores. Superimposed on this broad peak of Delta14C are several rapid excursions, the largest of which occurs between 44.3 and 43.3 ka. Between 26 and 11 ka, atmospheric Delta14C decreased from approximately 700 to approximately 100 per mil, modulated by numerous minor excursions. Carbon cycle models suggest that the major features of this record cannot be produced with solar or terrestrial magnetic field modulation alone but also require substantial fluctuations in the carbon cycle.

Acute identification of cranial burst fracture: comparison between CT and MR imaging findings.

BACKGROUND AND PURPOSE: Scalp swelling associated with cranial burst fracture, a widely diastatic skull fracture of infants associated with dural laceration and acute cerebral extrusion, may be confused with that of a simple subgaleal hematoma. Both conditions can also be associated with hemorrhagic shock. We sought to improve the early evaluation of infants believed to have sustained cranial burst fracture by including MR imaging, since this study clearly delineates the dural-cortical interface, the site of injury. METHODS: Seven infants aged 1 through 11 months who sustained cranial burst fractures, all initially imaged with skull radiography and CT, were studied or treated from 1992 through 1996. MR imaging was obtained after resuscitation and stabilization. RESULTS: Surgery or autopsy confirmed MR findings (dural laceration and extracalvarial cerebral tissue) in all seven infants. CONCLUSION: MR imaging allows early diagnosis of skull fracture associated with acute cerebral extrusion.

The enigma of lambdoid positional molding.

One hundred and twenty-one consecutive patients presenting to the Children's National Medical Center with lambdoid positional molding (LPM) were reviewed. Clinical features included unilateral occipital flattening and alopecia and forward displacement of the ipsilateral ear, forehead, and maxilla. Head tilt and tightness of the ipsilateral sternocleidomastoid muscle were common. An unexplained preponderance of LPM was found in males (74%) and on the right side (72%), both findings statistically significant (p < 0.001). Importantly, a variety of other abnormalities were seen with LPM: torticollis (41%), large head circumference (40), excess extra-axial cerebrospinal fluid (35), developmental delay (19), and other CNS abnormalities (20%). Systemic problems affecting the mobility were also common. Only 3 patients had craniosynostosis, and only 2 with LPM required surgery for severe cosmetic deformities. An apparent increase in the incidence of LPM was attributed to current recommendations to keep infants supine to decrease the risk of sudden infant death syndrome, overutilization of infant carriers similar to cradleboards of earlier cultures, and neonatal medical problems resulting in relative immobility. No evidence was found to support the concept that LPM causes compressive brain pathology; thus, surgical treatment is not required for such fears. Further, the sequelae of underlying CNS and systemic problems associated with LPM would not be corrected by opening unfused sutures, but could even be misinterpreted as complications of surgery.

Intracranial neurological injuries associated with orbital fracture.

We attempted to define the central nervous system (CNS) concomitants of various types of orbital fractures in children by reviewing the records of 95 inpatients with admission diagnoses including orbital fracture who presented to the Children's National Medical Center from 1987 through 1994. Patients were divided into three age groups: group I: 0-5 years; group II: 6-12 years; group III: older than 12 years. Orbital fractures were classified by location: roof alone (A); orbital roof plus another orbital wall (B), and orbital fractures sparing the roof (C). Mechanisms of injury included falls (F), motor vehicle accidents (M), and blunt injuries (S). Admission Glasgow Coma Scale (GCS), neurosurgical intervention, nature of associated intracranial injury, and presence of residual neurologic deficit were recorded. Group I included 38 patients, while groups II and III included 28 and 29, respectively. There were 61 boys and 34 girls. Most fractures confined to the roof occurred in group I patients (12 of 16 fractures; 75%). Twenty-four of the 38 group I patients (63%) sustained orbital fractures involving the roof compared to 12 (43%) and 6 (21%) in groups II and III, respectively. Children with orbital fractures involving the roof and another orbital wall, regardless of age, had lower admission GCS. Over half of type B fracture patients (19/26) were involved in motor vehicle accidents. Intracranial injuries were identified in 26 of the 73 patients (36%) whose CT included the brain. Fifteen of 26 patients (58%) with intracranial injuries sustained fractures involving the orbital roof, but only 3 of these had a type A fracture. Seven of the patients with intracranial injury required emergent neurosurgical procedures. Younger children with maxillofacial injury sparing the orbital roof appear more likely to have coexisting intracranial injury, as reflected by CT findings and GCS on admission, than their older cohorts with similar injuries. Fracture of more than one orbital wall greatly increases risk of concurrent intracranial injury in all age groups.

Comparison of scintigraphy and lactulose breath hydrogen test for assessment of orocecal transit: lactulose accelerates small bowel transit.

UNLABELLED: The lactulose breath test (LBT) and gastroenterocolonic scintigraphy (GECS) can both be used to measure orocecal transit time (OCTT). The aims of this study were (1) to measure OCTT by LBT and GECS and (2) to determine whether lactulose alters orocecal transit. METHODS: Eight normal subjects underwent simultaneous breath hydrogen testing, GECS, and duodenal manometry while receiving either 10 g lactulose or placebo with a radiolabeled solid/liquid test meal during two studies. There was a good correlation between OCTT by LBT and GECS when performed simultaneously (r = 0.95; P < 0.001). OCTT by GECS with lactulose was significantly faster (P = 0.004) than by GECS without lactulose, despite no change in gastric emptying of liquids and slowing of gastric emptying of solids (P = 0.02). The postprandial duodenal motility index was greater with lactulose than with placebo (P = 0.031). This study demonstrates that LBT and GECS (without lactulose) are not equivalent measures of OCTT. The standard LBT accelerates OCTT and slows gastric emptying. Therefore, lactulose has a direct accelerating effect on small intestinal transit.

Radiological and clinical criteria for the management of epidural hematomas in children.

OBJECTIVE: Modern neuroimaging and intensive care permit precise delineation and specific treatment of head injury. Children sustaining cranial trauma associated with epidural hematoma (EDH) represent a heterogeneous group with a variety of clinical outcomes. Treatment consists of simple observation or surgical evacuation. We attempted to define radiological characteristics of the EDH patients that underwent surgical evacuation. METHODS: We reviewed the records and computed tomography scans of 33 children sustaining cranial trauma associated with EDH treated at the Children's National Medical Center between October 1990 and August 1994. The radiological and clinical characteristics of children treated surgically (n = 13) and nonsurgically (n = 20) were compared. RESULTS: Mass effect, a temporal clot location, thickness, length and volume of the clot, and midline shift (p < 0.05) differed significantly between groups. The most important radiological parameters in determining the therapeutic intervention were thickness, midline shift, mass effect, and EDH location. A thickness of the EDH > 18 mm, a midline shift >4 mm, and moderate or severe mass effect correctly predicted therapy in 29 out of 33 patients. By adding the location as a fourth parameter, therapy was accuratly predicted in 31 of 33 patients. Mechanism of injury, interval from injury to initial computed tomography scan, age, sex, Glasgow coma score on admission, or lengths of hospital and intensive care unit stays were not significantly different between groups. CONCLUSION: Although radiological criteria predict surgical intervention for larger EDH, patients harboring intermediate-size EDH will continue to require careful individualized clinical judgement.

Association of a suprasellar mass and intraocular retinoblastoma: a variant of pineal trilateral retinoblastoma?

OBJECTIVE AND IMPORTANCE: 'Trilateral retinoblastoma' designates the association of bilateral retinoblastomas with an ectopic (non-metastatic) intracranial primitive neuroectodermal tumor (PNET). Although the intracranial tumor, usually located in the pineal region, is seen 2-3 years after discovery of the bilateral ocular tumors, variant presentations do occur. The intraocular tumor can be unilateral, and the intracranial tumor can be suprasellar, presenting before the retinal lesions. CLINICAL PRESENTATION: A 4-month-old boy presented with irritability, vomiting and nystagmus. Head CT revealed a large calcified sellar-suprasellar mass. Ocular examination disclosed white macular lesions in the right fundus. He was taken to surgery where subtotal resection of the sellar-suprasellar mass was achieved. Microscopic examination showed a primitive, small, round, blue cell tumor consistent with retinoblastoma. The right ocular lesions, also consistent with retinoblastoma, were treated by cryosurgery. CONCLUSION: The appearance of a suprasellar PNET can precede the appearance of retinal masses in retinoblastoma. The literature suggests that patients with 'sellar' trilateral retinoblastoma have characteristics that differ from patients with a pineal region trilateral retinoblastoma: the intracranial mass more often presents initially; it occurs at a younger age; it is predominant in females, and is more often associated with unilateral ocular lesions. Retinal screening of patients with suprasellar PNET and other atypically located PNETs may disclose more cases of sellar 'trilateral retinoblastoma' and hereditary retinoblastomas. This will have implications on genetic counseling as siblings harboring the disease may be diagnosed and treated at an earlier stage.

Cranial burst fracture in infants: acute recognition and management.

In the past, the diagnosis of "growing skull fracture" or "diastatic fracture" has included a subset of injuries better referred to as "cranial burst fracture." Cranial burst fracture, typically associated with severe injury in infants less than 1 year of age, is a closed, widely diastatic skull fracture accompanied by acute cerebral extrusion outside the calvarium. We treated 11 such infants at the LeBonheur Children's Medical Center and 2 at the Children's National Medical Center from January 1986 through December 1994. Infants ranged in age from 1 to 17 months, with an average age of 5.7 months. All presented with marked scalp swelling and a Glasgow Coma Scale score of 10 or less. Twelve had a history consistent with severe injury (motor vehicle accident, 7, abuse 5). The cause of injury in one patient remains unproven. Surgery (reduction of herniated cerebral tissue, repair of large dural laceration, and cranioplasty) was usually performed within 10 days of injury, a time period long enough to assure hemodynamic stability and resolution of acute cerebral swelling, yet sufficiently brief to avoid the chronic changes (scarring, parasitization of scalp vessels by damaged cortex) associated with a "growing skull fracture." Prompt repair of cranial burst fracture may prevent ongoing brain injury such as has been neuropathologically demonstrated in patients with "growing skull fracture." Magnetic resonance imaging establishes the diagnosis of cranial burst fracture in equivocal cases, rendering unnecessary a "waiting period" to see if scalp swelling resolves. Our experience, together with information in the neuropathological and neurosurgical literature, suggests that cranial burst fracture is associated with severe trauma, requires expeditious treatment, and has been underdiagnosed in the past, leading to "growing skull fracture," a condition requiring more extensive surgery.

Pediatric cerebellar hemorrhages.

Cerebellar hemorrhage is a devastating condition with morbidity and mortality related not only to the etiology of the hemorrhage, but also to the timing of the intervention. Sixteen consecutive pediatric patients with acute cerebellar hemorrhages are presented: 6 had vascular abnormalities, 3 had tumors, and 2 had hemorrhages of unknown etiology. Thirteen of the 16 patients survived with only 1 of the 13 having persistent vegetative state as a neurologic outcome. Six of 8 patients presenting in a moribund condition had good outcomes, and 3 of 4 patients presenting with fixed and dilated pupils also had good outcomes. Thus, in contrast to adults, rapid evaluation by CT scanning, followed by the judicious use of ventricular drainage and prompt surgical treatment, have resulted in favorable outcomes in pediatric patients despite their poor clinical presentations. None of the neonates having cerebellar hemorrhages required surgical intervention; their courses could be followed clinically and with transfontanel ultrasound.

Childhood survival of atlantooccipital dislocation: underdiagnosis, recognition, treatment, and review of the literature.

Traumatic childhood atlantooccipital dislocation (AOD) may be overlooked, especially in patients with concomitant closed head injury and multiple trauma. We diagnosed and treated 4 children with traumatic AOD seen in less than a 2-year period. We found published descriptions of only 15 other survivors of childhood traumatic AOD in the literature. Clinical histories, radiographic findings, treatment, outcome, and complications in these 15 children as well as our 4 patients were reviewed. The age distribution of childhood AOD survivors (average age 6.8 years) closely resembles that of pediatric multiple trauma patients. Early diagnosis of traumatic AOD hinges on precise interpretation of the lateral cervical radiograph. Longitudinal AOD was seen most often. Usually these children presented with cranial nerve palsies, major motor deficits, and depressed level of consciousness. Most underwent posterior atlantooccipital fusion. Outcome varied from normal neurological function to prolonged ventilator dependency and delayed demise. AOD must be diagnosed early to avoid attributing potentially reversible neurologic changes to irreversible injuries since closed head injury and high spinal cord dysfunction may be confused clinically and the outcome of a patient with AOD is unpredictable.

The disposition and cerebrospinal fluid penetration of morphine and its two major glucuronidated metabolites in adults undergoing lumbar myelogram.

STUDY OBJECTIVE: To determine the pharmacokinetic disposition of morphine and its two major glucuronidated metabolites, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G), in serum and their penetration into cerebrospinal fluid (CSF). DESIGN: A single-dose, open-label pharmacokinetic study. SETTING: The Memphis Neurosciences Center at Methodist Hospital. PATIENTS: Twenty patients undergoing a diagnostic lumbar myelogram. INTERVENTIONS: All patients received morphine sulfate 10 mg intramuscularly approximately 1.5 hours before the procedure. MEASUREMENTS AND MAIN RESULTS: Three blood samples were drawn after the dose and a CSF sample was drawn immediately after lumbar puncture. The mean +/- standard deviation for the half-life of morphine was 2.8 +/- 1.4 hours. The apparent half-lives of M6G and M3G were 5.7 +/- 3.1 and 6.3 +/- 2.2 hours, respectively, and were inversely related to the estimated creatinine clearance (r = -0.61, p < 0.007 and r = -0.69, p < 0.002, respectively). The mean concentrations of morphine, M6G, and M3G in the CSF (collection time 1.5 +/- 0.32 hrs, n = 19) were 3.1 +/- 3.7, 12.5 +/- 17.6, and 19.6 +/- 16.1 nmol/L, respectively. CONCLUSIONS: Elderly patients and patients with renal dysfunction receiving morphine may experience prolonged analgesic and adverse effects secondary to a decrease in the clearance of M6G.

A Large Drop in Atmospheric 14C/12C and Reduced Melting in the Younger Dryas, Documented with 230Th Ages of Corals.

Paired carbon-14 ((14)C) and thorium-230((230)Th) ages were determined on fossil corals from the Huon Peninsula, Papua New Guinea. The ages were used to calibrate part of the (14)C time scale and to estimate rates of sea-level rise during the last deglaciation. An abrupt offset between the (14)C and (230)Th ages suggests that the atmospheric (14)C/(12)C ratio dropped by 15 percent during the latter part of and after the Younger Dryas (YD). This prominent drop coincides with greatly reduced rates of sea-level rise. Reduction of melting because of cooler conditions during the YD may have caused an increase in the rate of ocean ventilation, which caused the atmospheric (14)C/(12)C ratio to fall. The record of sea-level rise also shows that globally averaged rates of melting were relatively high at the beginning of the YD. Thus, these measurements satisfy one of the conditions required by the hypothesis that the diversion of meltwater from the Mississippi to the St. Lawrence River triggered the YD event.

Pharmacokinetic and tissue residue characteristics of fenprostalene, a prostaglandin F2 alpha analog, in swine.

Fenprostalene, a prostaglandin F2 alpha analog, can be used to induce parturition in swine. As part of the approval process for that indication, pharmacokinetic characteristics of the absorption and elimination of fenprostalene and the depletion of drug residues from the principal edible tissues of swine were studied. Blood samples, urine, and feces were collected from 8 gilts (body weight, 95 +/- 1.7 kg) for up to 72 hours after a single dose of 0.5 mg of 13,14-[3H]-fenprostalene in polyethylene glycol-400 was administered SC. At intervals of 24, 48, 72, and 168 hours after dosing, 2 gilts each were killed, and samples of liver, kidney, muscle, and abdominal fat were obtained for analysis. The mean (+/- SEM) maximal concentration of fenprostalene radioequivalents in plasma (0.41 +/- 0.05 nanogram-equivalents/ml; n = 8) was observed at 12 hours and decreased biexponentially, with half-lives of approximately 8 hours and 9 days. Mean cumulative recovery (n = 4) of the administered dose by 72 hours was 61.2 +/- 5.9% in urine and 18.5 +/- 2.6% in feces. The highest tissue fenprostalene concentration was in kidneys and liver, probably reflecting the role of those organs in excreting fenprostalene. Rates of depletion of fenprostalene equivalents from the injection site, kidneys, and liver were comparable with those previously observed in cattle. The composition of residue in the liver of 2 gilts slaughtered 12 hours after SC administration of [3H]-fenprostalene was examined in a second study. Results suggested that approximately 4% of the total residue was pharmacologically potent fenprostalene or the carboxylic acid form of fenprostalene.(ABSTRACT TRUNCATED AT 250 WORDS)

Extinction of Harrington's mountain goat.

Keratinous horn sheaths of the extinct Harrington's mountain goat, Oreamnos harringtoni, were recovered at or near the surface of dry caves of the Grand Canyon, Arizona. Twenty-three separate specimens from two caves were dated nondestructively by the tandem accelerator mass spectrometer (TAMS). Both the TAMS and the conventional dates indicate that Harrington's mountain goat occupied the Grand Canyon for at least 19,000 years prior to becoming extinct by 11,160 +/- 125 radiocarbon years before present. The youngest average radiocarbon dates on Shasta ground sloths, Nothrotheriops shastensis, from the region are not significantly younger than those on extinct mountain goats. Rather than sequential extinction with Harrington's mountain goat disappearing from the Grand Canyon before the ground sloths, as one might predict in view of evidence of climatic warming at the time, the losses were concurrent. Both extinctions coincide with the regional arrival of Clovis hunters.

Cation-ratio and accelerator radiocarbon dating of rock varnish on mojave artifacts and landforms.

The first accelerator radiocarbon dates of rock varnishes are reported along with potassium/argon ages of lava flows and conventional radiocarbon dates of pluvial lake shorelines, in an empirical calibration of rock varnish K(+) + Ca(2+)/Ti(4+) ratios with age in the Mojave Desert, eastern California. This calibration was used to determine the cation-ratio dates of 167 artifacts. Although cation-ratio dating is an experimental method, some dates suggest human occupation of the Mojave Desert in the late Pleistocene.

Holocene age of the Yuha burial: direct radiocarbon determinations by accelerator mass spectrometry.

The view that human populations may not have arrived in the Western Hemisphere before about 12,000 radiocarbon yr BP has been challenged by claims of much greater antiquity for a small number of archaeological sites and human skeleton samples. One such site is the Homo sapiens sapiens cairn burial excavated in 1971 from the Yuha desert, Imperial County, California. Radiocarbon analysis of caliche coating one of the bones of the skeleton yielded a radiocarbon age of 21,500 +/- 1,000 yr BP, while radiocarbon and uranium series analyses of caliche coating a cairn boulder yielded ages of 22,125 +/- 400 and 19,000 +/- 3,000 yr BP, respectively. The late Pleistocene age assignment to the Yuha burial has been challenged by comparing the cultural context of the burial with other cairn burials in the same region, on the basis of the site's geomorphological context and from radiocarbon analyses of soil caliches. In rebuttal, arguments in defence of the original age assignment have been presented as well as an amino acid recemization analysis on the Yuha skeleton indicating an age of 23,600 +/- 2,600 yr BP. The tandem accelerator mass spectrometer at the University of Arizona has now been used to measure the ratio of 14C/13C in several organic and inorganic fractions of post-cranial bone from the Yuha H. sapiens sapiens skeleton. Isotope ratios from six chemical fractions all yielded radiocarbon ages for the skeleton of less than 4,000 yr BP. These results indicate that the Yuha skeleton is of Holocene age, in agreement with the cultural context of the burial, and in disagreement with the previously assigned Pleistocene age of 19,000-23,000 yr.

Lung cancer detection using a miniature sodium iodide detector and cobalt-57 bleomycin.

A small sodium iodide scintillation detector was designed for insertion through a fiberoptic bronchoscope to detect and localize sites of deposition of cobalt-57 bleomycin in lung cancer. The detector was used in 40 diagnostic studies of 34 patients; 21 of the patients had tumors. We compared the sensitivity, specificity, accuracy, and predictive value of the detector to those of plain chest x-ray films and bronchoscopy in detecting tumors. Sensitivity and specificity for the detector were 68 percent and 80 percent, respectively; for bronchoscopy, 72 percent and 100 percent; and for roentgenograms, 80 percent and 53 percent. Sensitivity for the detector and bronchoscopy combined was 92 percent. The detector succeeded in locating nonvisible submucosal and extraluminal tumors, and may contribute to early diagnosis and more accurate staging of lung cancer.