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Repetitive transcranial magnetic stimulation (rTMS) is a promising, innovative, and non-invasive therapy used clinically. Efficacy of rTMS has been demonstrated to ameliorate psychiatric disorders and neuropathic pain through neuromodulation of affected neural circuits. However, little is known about the mechanisms and the specific neural circuits via which rTMS facilitates these functional effects. The aim of this study was to begin revealing the mechanisms by which rTMS may tap into existing neural circuits, by using a well characterized spinal motor circuit – the phrenic circuit. Here we hypothesized that rTMS can be used to enhance phrenic motoneuron excitability in anesthetized Sprague Dawley rats. Multiple acute rTMS protocols were used revealing 10 Hz rTMS protocol induced a robust, long-lasting increase in phrenic motoneuron excitability, functionally evaluated by diaphragm motor evoked potentials (59.1 ± 21.1 % of increase compared to baseline 60 min after 10 Hz protocol against 6.0 ± 5.8 % (p = 0.007) for Time Control, −5.8 ± 7.4 % (p < 0.001) for 3 Hz, and 5.2 ± 12.5 % (p = 0.008) for 30 Hz protocols). A deeper analyze allowed to discriminate “responder” and “non-responder” subgroups among 10 Hz rTMS treated animals. Intravenous injections of GABA(A) and GABA(B) receptor agonists prior to 10 Hz rTMS treatment, abolished the enhanced phrenic motoneuron excitability, suggesting GABAergic input plays a mechanistic role in rTMS-induced phrenic excitability. These data demonstrate that a single high frequency rTMS protocol at 10 Hz increases phrenic motoneuron excitability, mediated by a local GABAergic “disinhibition”. By understanding how rTMS can be used to affect neural circuits non-invasively we can begin to harness the therapeutic potential of this neuromodulatory strategy to promote recovery after disease or injury to the central nervous system.

A cluster of cefepime-induced neutropenia (CIN) was identified from June 2017 to May 2018 in a regional outpatient parenteral antimicrobial therapy population. Our data suggest prolonged courses of cefepime (≥2 weeks), administered by rapid intravenous push, were associated with a higher risk of CIN.

Neural stem cells (NSCs) are a valuable tool for the study of neural development and function as well as an important source of cell transplantation strategies for neural disease. NSCs can be used to study how neurons acquire distinct phenotypes and how the interactions between neurons and glial cells in the developing nervous system shape the structure and function of the CNS. NSCs can also be used for cell replacement therapies following CNS injury targeting astrocytes, oligodendrocytes, and neurons. With the availability of patient-derived induced pluripotent stem cells (iPSCs), neurons prepared from NSCs can be used to elucidate the molecular basis of neurological disorders leading to potential treatments. Although NSCs can be derived from different species and many sources, including embryonic stem cells (ESCs), iPSCs, adult CNS, and direct reprogramming of nonneural cells, isolating primary NSCs directly from fetal tissue is still the most common technique for preparation and study of neurons. Regardless of the source of tissue, similar techniques are used to maintain NSCs in culture and to differentiate NSCs toward mature neural lineages. This chapter will describe specific methods for isolating and characterizing multipotent NSCs and neural precursor cells (NPCs) from embryonic rat CNS tissue (mostly spinal cord) and from human ESCs and iPSCs as well as NPCs prepared by reprogramming. NPCs can be separated into neuronal and glial restricted progenitors (NRP and GRP, respectively) and used to reliably produce neurons or glial cells both in vitro and following transplantation into the adult CNS. This chapter will describe in detail the methods required for the isolation, propagation, storage, and differentiation of NSCs and NPCs isolated from rat and mouse spinal cords for subsequent in vitro or in vivo studies as well as new methods associated with ESCs, iPSCs, and reprogramming.

BackgroundMany healthcare organizations have developed processes for supporting the emotional needs of patients and their families after medical errors or adverse events. However, the clinicians involved in such events may become "second victims" and frequently experience emotional harm that impacts their personal and professional lives. Many "second victims," particularly physicians, do not receive adequate support by their organizations.MethodsA multidisciplinary team was assembled to create a clinician peer support program (PSP) at a large academic medical center including both adult and pediatric hospitals. A curriculum was developed to train clinicians to provide support to their peers based on research of clinician response to adverse events, utilization of various support resources, and clinician resiliency and ways to enhance natural resilience. Between April 2014 and January 2017, 165 individuals were referred to the program including 68 (41.2%) residents, 17 (10.3%) fellows, 70 (42.4%) faculty members, 6 (3.6%) nurse practitioners/physician assistants, and 4 (2.4%) certified registered nurse anesthetists. An average of 4.8 individuals were referred per month (range = 0-12). Of the 165 clinicians referred, 17 (10.3%) declined follow-up from the program. Individuals receiving support had a median of two interactions (range = 1-10). Among those receiving support from the clinician PSP, 16 (10.8%) required referral to a higher level of support.ConclusionsWe describe the multiple steps necessary to create a successful PSP focused on physicians and midlevel providers. There is an unmet need to provide support to this group of healthcare providers after medical errors and adverse events.

Unilateral cervical C2 hemisection (C2Hx) is a classic model of spinal cord injury (SCI) for studying respiratory dysfunction and plasticity. However, most previous studies were performed under anesthesia, which significantly alters respiratory network. Therefore, the goal of this work was to assess spontaneous diaphragm recovery post-C2Hx in awake, freely behaving animals. Adult rats were chronically implanted with diaphragm EMG electrodes and recorded during 8 weeks post-C2Hx. Our results reveal that ipsilateral diaphragm activity partially recovers within days post-injury and reaches pre-injury amplitude in a few weeks. However, the full extent of spontaneous ipsilateral recovery is significantly attenuated by anesthesia (ketamine/xylazine, isoflurane, and urethane). This suggests that the observed recovery may be attributed in part to activation of NMDA receptors which are suppressed by anesthesia. Despite spontaneous recovery in awake animals, ipsilateral hemidiaphragm dysfunction still persists: i) Inspiratory bursts during basal (slow) breathing exhibit an altered pattern, ii) the amplitude of sighs – or augmented breaths – is significantly decreased, and iii) the injured hemidiaphragm exhibits spontaneous events of hyperexcitation. The results from this study offer an under-appreciated insight into spontaneous diaphragm activity and recovery following high cervical spinal cord injury in awake animals.

Limited data are available regarding the spinal projections of afferent fibers in the phrenic nerve. We describe a method that robustly labels phrenic afferent spinal projections in adult rats. The proximal end of the cut phrenic nerve was secured in a microtube filled with a transganglionic tracer (cholera toxin β-subunit, CT-β, or Cascade Blue) and tissues harvested 96-hrs later. Robust CT-β labeling occurred in C3-C5 dorsal root ganglia cell bodies and phrenic afferent projections were identified in the mid-cervical dorsal horn (laminae I-III), intermediate gray matter (laminae IV, VII) and near the central canal (laminae X). Afferent fiber labeling was reduced or absent when CT-β was delivered to the intrapleural space or directly to the hemidiaphragm. Soaking the phrenic nerve with Cascade Blue also produced robust labeling of mid-cervical dorsal root ganglia cells bodies, and primary afferent fibers were observed in spinal grey matter and dorsal white matter. Our results show that the ‘nerve soak’ method effectively labels both phrenic motoneurons and phrenic afferent projections, and show that primary afferent project throughout the ipsilateral mid-cervical gray matter.

Cervical spinal cord injuries (SCI) result in devastating functional consequences, including respiratory dysfunction. This is largely attributed to the disruption of phrenic pathways, which control the diaphragm. Recent work has identified spinal interneurons as possible contributors to respiratory neuroplasticity. The present work investigated whether transplantation of developing spinal cord tissue, inherently rich in interneuronal progenitors, could provide a population of new neurons and growth-permissive substrate to facilitate plasticity and formation of novel relay circuits to restore input to the partially denervated phrenic motor circuit. One week after a lateralized, C3/4 contusion injury, adult Sprague-Dawley rats received allografts of dissociated, developing spinal cord tissue (from rats at gestational days 13-14). Neuroanatomical tracing and terminal electrophysiology was performed on the graft recipients 1 month later. Experiments using pseudorabies virus (a retrograde, transynaptic tracer) revealed connections from donor neurons onto host phrenic circuitry and from host, cervical interneurons onto donor neurons. Anatomical characterization of donor neurons revealed phenotypic heterogeneity, though donor-host connectivity appeared selective. Despite the consistent presence of cholinergic interneurons within donor tissue, transneuronal tracing revealed minimal connectivity with host phrenic circuitry. Phrenic nerve recordings revealed changes in burst amplitude after application of a glutamatergic, but not serotonergic antagonist to the transplant, suggesting a degree of functional connectivity between donor neurons and host phrenic circuitry that is regulated by glutamatergic input. Importantly, however, anatomical and functional results were variable across animals, and future studies will explore ways to refine donor cell populations and entrain consistent connectivity.

There is growing interest in the use of neural precursor cells to treat spinal cord injury (SCI). Despite extensive pre-clinical research, it remains unclear as to which donor neuron phenotypes are available for transplantation, whether the same populations exist across different sources of donor tissue (e.g., developing tissue vs. cultured cells), and whether donor cells retain their phenotype once transplanted into the hostile internal milieu of the injured adult spinal cord. In addition, while functional improvements have been reported after neural precursor transplantation post-SCI, the extent of recovery is limited and variable. The present work begins to address these issues by harnessing ventrally derived excitatory pre-motor V2a spinal interneurons (SpINs) to repair the phrenic motor circuit after cervical SCI. Recent studies have demonstrated that Chx10-positive V2a SpINs contribute to anatomical plasticity within the phrenic circuitry after cervical SCI, thus identifying them as a therapeutic candidate. Building upon this discovery, the present work tests the hypothesis that transplantation of neural progenitor cells (NPCs) enriched with V2a INs can contribute to neural networks that promote repair and enhance respiratory plasticity after cervical SCI. Cultured NPCs (neuronal and glial restricted progenitor cells) isolated from E13.5 Green fluorescent protein rats were aggregated with TdTomato-mouse embryonic stem cell-derived V2a INs in vitro, then transplanted into the injured cervical (C3-4) spinal cord. Donor cells survive, differentiate and integrate with the host spinal cord. Functional diaphragm electromyography indicated recovery 1 month following treatment in transplant recipients. Animals that received donor cells enriched with V2a INs showed significantly greater functional improvement than animals that received NPCs alone. The results from this study offer insight into the neuronal phenotypes that might be effective for (re)establishing neuronal circuits in the injured adult central nervous system.

Cervical spinal cord injury (cSCI) disrupts bulbospinal projections to motoneurons controlling the upper limbs, resulting in significant functional impairments. Ongoing clinical and experimental research has revealed several lines of evidence for functional neuroplasticity and recovery of upper extremity function after SCI. The underlying neural substrates, however, have not been thoroughly characterized. The goals of the present study were to map the intraspinal motor circuitry associated with a defined upper extremity muscle, and evaluate chronic changes in the distribution of this circuit following incomplete cSCI. Injured animals received a high cervical (C2) lateral hemisection (Hx), which compromises supraspinal input to ipsilateral spinal motoneurons controlling the upper extremities (forelimb) in the adult rat. A battery of behavioral tests was used to characterize the time course and extent of forelimb motor recovery over a 16 week period post-injury. A retrograde transneuronal tracer – pseudorabies virus – was used to define the motor and pre-motor circuitry controlling the extensor carpi radialis longus (ECRL) muscle in spinal intact and injured animals. In the spinal intact rat, labeling was observed unilaterally within the ECRL motoneuron pool and within spinal interneurons bilaterally distributed within the dorsal horn and intermediate gray matter. No changes in labeling were observed 16 weeks post-injury, despite a moderate degree of recovery of forelimb motor function. These results suggest that recovery of the forelimb function assessed following C2Hx injury does not involve recruitment of new interneurons into the ipsilateral ECRL motor pathway. However, the functional significance of these existing interneurons to motor recovery requires further exploration.

Several devices are available to measure vertical jump (VJ) height based on flight time, VJ reach height, or ground reaction forces. The purpose of this study was to determine the accuracy of a VJ mat for measuring flight time and VJ height compared with a VJ tester or a force plate. Seventeen men and 18 women (X ± SD; age = 20.9 ± 0.7 years, height = 176.1 ± 0.9 cm, weight = 72.6 ± 13.5 kg) served as subjects. Subjects performed counter-movement vertical jumps while standing on both a force plate (1,000 Hz) and a VJ mat. A Vertec VJ tester was used to measure jump reach. Compared with the force plate, the VJ mat reported greater VJ height (VJ mat = 0.50 ± 0.12 m, force plate = 0.34 ± 0.10 m) and flight time (VJ mat = 0.629 ± 0.078 seconds, force plate = 0.524 ± 0.077 seconds). Comparison of VJ heights from the VJ mat and the Vertec revealed no significant differences (Vertec = 0.48 ± 0.11 m). Regression analyses indicated strong relationships between testing methods and suggested that high VJ performances may be underestimated with the VJ mat. This particular VJ mat compared favorably with the Vertec but not the force plate. It seems that the different flight times derived from the VJ mat may permit the VJ mat to be in closer agreement with VJ heights from the Vertec. Also, the VJ mat may not be an appropriate tool for assessing high VJ performances (i.e., ≥0.70 m; ≈28 inches). Practitioners and researchers using similar VJ mats may not obtain accurate flight times and may underestimate high performers.

RationaleThe demographic, physiological, and computed tomography (CT) features associated with pneumothorax in smokers with and without chronic obstructive pulmonary disease (COPD) are not clearly defined.ObjectivesWe evaluated the hypothesis that pneumothorax in smokers is associated with male sex, tall and thin stature, airflow obstruction, and increased total and subpleural emphysema.MethodsThe study included smokers with and without COPD from the COPDGene Study, with quantitative chest CT analysis. Pleural-based emphysema was assessed on the basis of local histogram measures of emphysema. Pneumothorax history was defined by subject self-report.Measurements and main resultsPneumothorax was reported in 286 (3.2%) of 9,062 participants. In all participants, risk of prior pneumothorax was significantly higher in men (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.08-2.22) and non-Hispanic white subjects (OR, 1.90; 95% CI, 1.34-2.69). Risk of prior pneumothorax was associated with increased percent CT emphysema in all participants and participants with COPD (OR, 1.04 for each 1% increase in emphysema; 95% CI, 1.03-1.06). Increased pleural-based emphysema was independently associated with risk of past pneumothorax in all participants (OR, 1.05 for each 1% increase; 95% CI, 1.01-1.10). In smokers with normal spirometry, risk of past pneumothorax was associated with non-Hispanic white race and lifetime smoking intensity (OR, 1.20 for every 10 pack-years; 95% CI, 1.09-1.33).ConclusionsAmong smokers, pneumothorax is associated with male sex, non-Hispanic white race, and increased percentage of total and subpleural CT emphysema. Pneumothorax was not independently associated with height or lung function, even in participants with COPD. Clinical trial registered with www.clinicaltrials.gov (NCT00608764).

Human immunodeficiency virus (HIV)-infected women are at increased risk of invasive cervical cancer; however, screening rates remain low. The objectives of this study were to analyze a quality improvement intervention to increase cervical cancer screening rates in an urban academic HIV clinic and to identify factors associated with inadequate screening. Barriers to screening were identified by a multidisciplinary quality improvement committee at the Washington University Infectious Diseases clinic. Several strategies were developed to address these barriers. The years pre- and post-implementation were analyzed to examine the clinical impact of the intervention. A total of 422 women were seen in both the pre-implementation and post-implementation periods. In the pre-implementation period, 222 women (53%) underwent cervical cancer screening in the form of Papanicolaou (Pap) testing. In the post-implementation period, 318 women (75.3%) underwent cervical cancer screening (p < 0.01). Factors associated with lack of screening included fewer visits attended (pre: 4.2 ± 1.5; post: 3.4 ± 1.4; p < 0.01). A multidisciplinary quality improvement intervention was successful in overcoming barriers and increasing cervical cancer screening rates in an urban academic HIV clinic.

Evaluate the efficacy of percutaneous vertebroplasty for severe vertebral body compression fractures. Over a period of 6 years and 8 months, 661 vertebroplasties were performed in 292 patients at our institution. Of these, 69 patients met our criteria for a severe vertebral body compression fracture defined as vertebral body collapse to less than one-third of the original height. Of the 69, 25 underwent single level vertebroplasty. Imaging features were then analyzed including location, extent of collapse, pattern of compression, pre- and post-kyphotic angle and adjacent disc height. Complications and clinical outcomes were then evaluated. Involved vertebra ranged from T6 to L5 with 60% at the thoracolumbar junction. Vertebral body collapse ranged from 30 to 14% (mean 22%) of original height. Pattern of collapse included 11/ 25 (44%) plana, 8/25 (32%) gibbus, and 6/25 (24%) H-shaped. Kyphotic angle before vertebroplasty ranged from 33–0° (mean 16°) with an average correction of 1.2° after vertebroplasty. Mean disc height before vertebroplasty was 7.3 mm above and 7.7 mm below. Complications included cement leak to the adjacent disc in 16 (64%) and the paravertebral soft tissues in 3 (12%). Cement leak into the proximal azygous vein was documented in one case. International Quality of Life Questionnaire VAS was completed before and after (6 weeks) the procedure by all but six patients. Mean pre-intervention VAS was reported as 7.00 (range 5–10, SD 1.73) and mean post-intervention VAS was reported as 5.11 (range 0–9, SD 2.56), demonstrating a statistically significant improvement in pain (P

The purpose of this study was to identify a clinical guideline for the evaluation of nonspecific abdominal pain (NSAP) using history, physical examination, laboratory analysis, acute abdominal series (AAS) radiographs, and nonenhanced helical computed tomography (NHCT) clinical predictor variables (CPVs).The setting of this study was at an urban emergency department (ED) with 70,000 yearly visits.This is an institutional review board-approved, prospective, observational study. The primary outcome variable was urgent intervention (UI), defined as a diagnosis requiring surgical or medical treatment to prevent death or major morbidity. Subjects underwent prompted history, physical, laboratory studies, AAS, and NHCT and were followed up to 6 months for ultimate diagnosis and outcome. CPVs were subjected to classification and regression tree analysis.One hundred sixty-five subjects were analyzed. Thirteen percent of subjects required UI within 24 hours of presentation; an additional 34% underwent elective interventions that mitigated morbidity or mortality. Four guideline models were generated. Model 1 consisted of history and physical, with a sensitivity of 25%, a specificity of 92%, a positive likelihood ratio of 3.17, and a negative likelihood ratio of 0.81. Model 2 consisted of model 1 with laboratory, with a sensitivity of 39%, a specificity of 88%, a positive likelihood ratio of 3.25, and a negative likelihood ratio of 0.69. Model 3 consisted of model 2 with AAS, with a sensitivity of 56%, a specificity of 81%, a positive likelihood ratio of 2.94, and a negative likelihood ratio of 0.54. Model 4 comprised all inputs, including NHCT, with a sensitivity of 92%, a specificity of 90%, a positive likelihood ratio of 9.2, and a negative likelihood ratio of 0.089. NHCT was the single most accurate CPV for UI.No clinical guideline was identified exclusive of NHCT that possessed adequate sensitivity for exclusion of UI. NHCT is a rational choice for decision support in the evaluation of NSAP and is likely the single most useful diagnostic adjunct available to augment the clinical evaluation.

This study sought to determine if obtaining an unenhanced abdominopelvic computed tomography (UHCT) scan alters the disposition of patients presenting to the Emergency Department (ED) with signs and symptoms of acute appendicitis. A convenience sample of 101 patients presenting with a clinical picture suggestive of appendicitis were prospectively enrolled. Emergency physicians (EPs) and general surgeons independently recorded their anticipated disposition of each patient as: discharge, admit for observation, or admit for appendectomy. A UHCT scan was then obtained and the patient's ultimate disposition recorded. EPs altered their dispositions after UHCT scanning in 35 patients (34.7%, 95% CI 25.4% to 44.0%), and general surgeons altered their dispositions in 27 patients (26.7%, 95% CI 18.1% to 35.3%). More patients underwent operative intervention than were originally selected by EPs [14 additional patients, (13.9%, 95% CI 7.1% to 20.6%)] or by surgeons [20 additional patients, (19.8%, 95% CI 12.0% to 27.6%)]. CT scan revealed alternative diagnoses in 20 patients (19.8%). UHCT scanning significantly alters patient disposition, and significantly increases the number of operative interventions performed in patients with suspected appendicitis. UHCT scanning may also identify alternate pathology that clinically mimics appendicitis.

To compare the percentages of normal magnetic resonance imaging (MRI) examination results and clinically significant knee abnormalities in patients referred for MRI of the knee by orthopaedic surgery residents and staff with those of patients referred by nonorthopaedic practitioners.Retrospective review of MRI findings.MRI reports of 754 patients (454 men and 300 women) were retrospectively reviewed; 373 patients were referred from the Department of Orthopaedic Surgery and 381 patients were referred from nonorthopaedic practitioners. The number of normal examination results, meniscal and ligament tears, chondral abnormalities, and Baker's cysts was tabulated and analyzed using a X-square injury analysis.The rate of normal results for nonorthopaedic practitioners was 33.9% (129 of 381) compared with 15.3% (57 of 373) for orthopaedic surgeons (P.001). Nonorthopaedic surgeons referred 69.4% (129 of 186) of the patients who had normal examination results. The positive finding for a lateral meniscus tear was 29.2% (109 of 373) for orthopaedic surgeons compared with 19.1% (73 of 381) for nonorthopaedic practitioners, which was statistically significant (P =.002) in regard to the distribution of injuries. No difference was found in other abnormalities assessed.Patients referred by nonorthopaedic practitioners had significantly more normal knee MRI examination results than did those referred by orthopaedic surgeons.

The purpose of this study was to evaluate the clinical significance of the "flat cava" sign on abdominal CT scans in hospitalized patients without trauma.CT scans of the abdomen of 500 inpatients imaged for a wide variety of nontraumatic indications were retrospectively reviewed for a flat cava sign. Two radiologists measured the maximal anteroposterior and transverse diameters of the inferior vena cava at four predetermined levels. The medical records of the subset of patients with a flat cava sign--defined as a maximal transverse-to-anteroposterior ratio of 3:1 or greater at one or more of the four levels--were reviewed for evidence of hypovolemia or hypotension.Seventy patients (14%; 48 women, 22 men) had a flat inferior vena cava present on at least one of the four levels. Of these 70 patients, 21 had definite and three had possible clinical evidence of hypotension or hypovolemia. A flat cava sign isolated to only one level was seen in 22 of the 70 patients, most commonly at the level just below the renal veins, and only four of these 22 patients had evidence of hypotension or hypovolemia.Of the 500 inpatients, 14% had a flat cava sign on at least one of the four levels examined on abdominal CT scans. The majority of these patients with a flat cava sign did not have hypotension or evidence of hypovolemia, but a minority (30%) did.

Background Antibiotics may interact with warfarin, increasing the risk for significant bleeding events. Methods This is a retrospective cohort study of veterans who were prescribed warfarin for 30 days without interruption through the US Department of Veterans Affairs between October 1, 2002 and September 1, 2008. Antibiotics considered to be high risk for interaction with warfarin include: trimethoprim/sulfamethoxazole (TMP/SMX), ciprofloxacin, levofloxacin, metronidazole, fluconazole, azithromycin, and clarithromycin. Low-risk antibiotics include clindamycin and cephalexin. Risk of bleeding event within 30 days of antibiotic exposure was measured using Cox proportional hazards regression, adjusted for demographic characteristics, comorbid conditions, and receipt of other medications interacting with warfarin. Results A total of 22,272 patients met inclusion criteria, with 14,078 and 8194 receiving high- and low-risk antibiotics, respectively. There were 93 and 36 bleeding events in the high- and low-risk groups, respectively. Receipt of a high-risk antibiotic (hazard ratio [HR] 1.48; 95% confidence interval [CI], 1.00-2.19) and azithromycin (HR 1.93; 95% CI, 1.13-3.30) were associated with increased risk of bleeding as a primary diagnosis. TMP/SMX (HR 2.09; 95% CI, 1.45-3.02), ciprofloxacin (HR 1.87; 95% CI, 1.42-2.50), levofloxacin (HR 1.77; 95% CI, 1.22-2.50), azithromycin (HR 1.64; 95% CI, 1.16-2.33), and clarithromycin (HR 2.40; 95% CI, 1.16-4.94) were associated with serious bleeding as a primary or secondary diagnosis. International normalized ratio (INR) alterations were common; 9.7% of patients prescribed fluconazole had INR value >6. Patients who had INR performed within 3-14 days of co-prescription were at a decreased risk of serious bleeding (HR 0.61; 95% CI, 0.42-0.88). Conclusions Warfarin users who are prescribed high-risk antibiotics are at higher risk for serious bleeding events. Early INR evaluation may mitigate this risk.

PURPOSE: To determine the accuracy and utility of unenhanced helical CT for suspected renal colic, using a pitch of either 2.5 or 3.0. METHODS: 59 consecutive patients underwent unenhanced helical CT. 5 mm contiguous images were obtained at a kVP of 120 and an mA of 260. Thirty-four patients were imaged at a pitch of 2.5, and 25 patients were imaged at a pitch of 3.0. Two radiologists, an attending (reader 1), and a second-year resident (reader 2), independently and retrospectively reviewed the CT images, blinded to the clinical outcome. The presence or absence of a ureteral stone was recorded and image quality was graded. A third radiologist determined accuracy for each reader. Average entrance exposure was estimated using a CT phantom at a variety of pitches. RESULTS: Overall sensitivity, specificity, and accuracy for reader 1 were 91, 96, and 93%. For reader 2, they were 86, 93, and 90%. There was no significant difference in accuracy using a pitch of 3.0 compared with 2.5 for either reader. Readers 1 and 2 rated image quality at 2.5 pitch as excellent for 88 and 76% of scans, respectively; at 3.0 pitch the scans were rated by both readers as excellent for 40% and acceptable for 60%. Average entrance exposures were estimated at 461, 553. and 913 mR at pitches of 3.0, 2.5, and 1.5. CONCLUSION: Increasing the pitch on unenhanced helical CT for suspected renal colic to 2.5 or 3.0 appears to be an effective method of reducing radiation dose. Although accuracy of the technique did not significantly change using a pitch of 3.0 in one group of patients, compared with a pitch of 2.5 in another group of patients, image quality did decrease.

Typical Findings Unenhanced helical images are obtained from the level of the T12 vertebral body to the pubic symphysis, using 5-mm collimation and a pitch of I .7, in one or more breath-holds. A ureteral stone is identified by following the ureter inferiorly to an area of calcification. This is most easily done by paging or scrolling through the images on the CT monitor. SecondWY signs are common and provide evidence that an acute obstructive process is present [2J (Fig. I ): these signs include hydronephrosis, hydroureter, perinephric edema, enlargement of the kidney, periureteric edema. and edema at

A primary malignant pulmonary hemangiopericytoma was diagnosed in a 45-year-old woman who complained of 10 months of cough and exertional dyspnea. One year after resection of the mass, a metastatic lesion was removed from the contralateral lung. The literature on this unusual pulmonary lesion is reviewed.

The purpose of this study was to determine the diagnostic accuracy of unenhanced helical CT scans in patients with a suspected acute appendicitis.Over a 20-month period, 109 adult patients with suspected acute appendicitis were referred by the emergency department for an unenhanced helical CT scan. Each scan was obtained in a single breath-hold from the T12 vertebral body to the public symphysis using a 5-mm collimation and a pitch of 1.6. No patients were given oral or IV contrast media. The primary CT criteria for diagnosing acute appendicitis was the identification of an appendix with a transverse diameter larger than 6 mm with associated periappendiceal inflammatory changes. The presence of an appendicolith was considered a secondary finding as was isolated periappendiceal inflammation; however, appendicitis was not diagnosed in such patients unless an enlarged appendix was definitely identified. Final diagnoses were established by surgical or clinical follow-up and were compared with the original CT reports.We found 66 true-negatives, 37 true-positives, four false-negatives, and two false-positives that yielded a sensitivity of 90%, a specificity of 97%, a positive predictive value of 95%, a negative predictive value of 95%, and an accuracy of 94%. An alternative diagnosis was established by an unenhanced helical CT scan in 24 patients (22%), which included cecal diverticulitis (seven patients), urinary tract disease (five patients), adnexal pathology (four patients), sigmoid diverticulitis (two patients), small bowel disease (three patients), right lower quadrant tumor (two patients), and an infected dialysis catheter (one patient).Unenhanced thin-section helical CT is an accurate, effective technique for diagnosing acute appendicitis.

T he abdominal mesenteries are primanly composed of fat through which run the major arteries, veins, and lymphatic vessels ofthe bowel. An alteration in the density of the mesenteric fat is often the principal clue of underlying mesenteric and bowel disease. We have coined the term “misty mesentery” to describe the CT appearance of mesenteric fat infiltrated by inflammatory cells, fluid (edema, lymph, and blood), tumor, and fibrosis. We descrbe a wide range of diseases that can produce a misty mesentery, and w f1 i an approach to the differential diagnosis by identifying specific patterns of involvement. Normal and “Misty” Mesentery Most individuals have sufficient mesenteric fat for CT to identify easily the smalland large-bowel mesenteries. Mesenteric fat is similar in density (-100 to -160 H) to the fat in subcutaneous and retroperitoneal spaces. The mesenteric vessels, surrounded by fat, are usually seen on end but may be visualized transversely as they course to the bowel wall. With infiltration of the mesentery by fluid or cells, the mean density of this fat increases to -40 to -60 H, and the mesenteric arteries and veins often lose their sharp interfaces. Depending on the nature and extent of the infiltration, mesenteric vessels may be either completely or partially effaced. A clue to mesenteric disease is often revealed along the visceral peritoneum as the edge of the mesentery becomes accentuated against the surrounding fat (Fig. 1).

The purpose of this study was to characterize the chest CT findings of North American paragonimiasis due to Paragonimus kellicotti in the largest (to our knowledge) case series reported to date and to compare the findings with those reported for paragonimiasis infections in other regions.A retrospective review was performed of chest CT examinations of eight patients with North American paragonimiasis treated at our institution between 2006 and 2010. Findings were characterized by site of involvement, including lungs and pleura, heart and pericardium, lymph nodes, and upper abdomen.The most common chest CT findings in this case series were pleural effusions and internal mammary and cardiophrenic lymphadenopathy. Pulmonary parenchymal findings included peripheral lung nodules of 1-3.5 cm in size with surrounding ground-glass opacity; many nodules had a linear track to the pleural surface that may correspond to the worm's burrow tunnel. Pericardial involvement (5/8 patients) and omental inflammation (5/7 patients), which are uncommon in Asian paragonimiasis, were common in this series.Pleural and pulmonary features of North American paragonimiasis are generally similar to those reported from Asia. The presence of a track between a pulmonary nodule and the pleura may help distinguish paragonimiasis from mimickers, including chronic eosinophilic pneumonia, tuberculosis, fungal infection, or malignancy. Pericarditis, lymphadenopathy, and omental inflammation were more common in our series than in reports on paragonimiasis from other regions. These differences may be related to the infecting parasite species or to the fact that radiologic examinations in the present series were performed relatively early in the course of infection.

The consequences of spinal cord injury (SCI) are often viewed as the result of white matter damage. However, injuries occurring at any spinal level, especially in cervical and lumbar enlargement regions, also entail segmental neuronal loss. Yet, the contributions of gray matter injury and plasticity to functional outcomes are poorly understood. The present study addressed this issue by investigating changes in respiratory function following bilateral C(3)/C(4) contusion injuries at the level of the phrenic motoneuron (PhMN) pool which in the adult rat extends from C(3) to C(5/6) and provides innervation to the diaphragm. Despite extensive white and gray matter pathology associated with two magnitudes of injury severity, ventilation was relatively unaffected during both quiet breathing and respiratory challenge (hypercapnia). On the other hand, bilateral diaphragm EMG recordings revealed that the ability to increase diaphragm activity during respiratory challenge was substantially, and chronically, impaired. This deficit has not been seen following predominantly white matter lesions at higher cervical levels. Thus, the impact of gray matter damage relative to PhMNs and/or interneurons becomes evident during conditions associated with increased respiratory drive. Unaltered ventilatory behavior, despite significant deficits in diaphragm function, suggests compensatory neuroplasticity involving recruitment of other spinal respiratory networks which may entail remodeling of connections. Transynaptic tracing, using pseudorabies virus (PRV), revealed changes in PhMN-related interneuronal labeling rostral to the site of injury, thus offering insight into the potential anatomical reorganization and spinal plasticity following cervical contusion.

Medications used to treat rheumatoid arthritis (RA) may confer an increased risk of infection. We conducted a retrospective cohort study of veterans with RA followed in the United States Department of Veterans Affairs health care system from October 1998 through September 2005. Risk of hospitalization for infection associated with tumor necrosis factor (TNF)-α antagonists therapy was measured using an extension of Cox proportional hazards regression, adjusting for demographic characteristics, comorbid illnesses, and other medications used to treat RA. A total of 20,814 patients met inclusion criteria, including 3796 patients who received infliximab, etanercept, or adalimumab. Among the study cohort, 1465 patients (7.0%) were hospitalized at least once for infection. There were 1889 hospitalizations for infection. The most common hospitalized infections were pneumonia, bronchitis, and cellulitis. Age and several comorbid medical conditions were associated with hospitalization for infection. Prednisone (hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.88-2.43) and TNF-α antagonist use (HR, 1.24; 95% CI, 1.02-1.50) were associated with hospitalization for infection, while the use of disease-modifying antirheumatic drugs (DMARDs) other than TNF-α antagonists was not. Compared to etanercept, infliximab was associated with risk for hospitalization for infection (HR, 1.51; 95% CI, 1.14-2.00), while adalimumab use was not (HR, 0.95; 95% CI, 0.68-1.33). In all treatment groups, rate of hospitalization for infection was highest in the first 8 months of therapy. We conclude that patients with RA who are treated with TNF-α antagonists are at higher risk for hospitalization for infection than those treated with other DMARDs. Prednisone use is also a risk factor for hospitalization for infection.

Despite extensive gray matter loss following spinal cord injury (SCI), little attention has been given to neuronal replacement strategies and their effects on specific functional circuits in the injured spinal cord. In the present study, we assessed breathing behavior and phrenic nerve electrophysiological activity following transplantation of microdissected dorsal or ventral pieces of rat fetal spinal cord tissue (FSC(D) or FSC(V), respectively) into acute, cervical (C2) spinal hemisections. Transneuronal tracing demonstrated connectivity between donor neurons from both sources and the host phrenic circuitry. Phrenic nerve recordings revealed differential effects of dorsally vs. ventrally derived neural progenitors on ipsilateral phrenic nerve recovery and activity. These initial results suggest that local gray matter repair can influence motoneuron function in targeted circuits following spinal cord injury and that outcomes will be dependent on the properties and phenotypic fates of the donor cells employed.

Paragonimiasis (human infections with the lung fluke Paragonimus westermani) is an important public health problem in parts of Southeast Asia and China. Paragonamiasis has rarely been reported from North America as a zoonosis caused by Paragonimus kellicotti. Paragonimus species have complex life cycles that require 2 intermediate hosts, namely, snails and crustaceans (ie, crabs or crayfish). Humans acquire P. kellicotti when they consume infected raw crayfish. Humans with paragonimiasis usually present with fever and cough, which, together with the presentation of hemoptysis, can be misdiagnosed as tuberculosis. Only 7 autochthonous cases of paragonimiasis have been previously reported from North America. Our study describes 3 patients with proven or probable paragonimiasis with unusual clinical features who were seen at a single medical center during an 18-month period. These patients acquired their infections after consuming raw crayfish from rivers in Missouri. It is likely that other patients with paragonimiasis have been misdiagnosed and improperly treated. Physicians should consider the possibility that patients who present with cough, fever, hemoptysis, and eosinophilia may have paragonimiasis.

Although monosynaptic bulbospinal projections to phrenic motoneurons have been extensively described, little is known about the organization of phrenic premotor neurons in the adult rat spinal cord. Because interneurons may play an important role in normal breathing and recovery following spinal cord injury, the present study has used anterograde and transneuronal retrograde tracing to study their distribution and synaptic relations. Exclusive unilateral, first-order labeling of the phrenic motoneuron pool with pseudorabies virus demonstrated a substantial number of second-order, bilaterally distributed cervical interneurons predominantly in the dorsal horn and around the central canal. Combined transneuronal and anterograde tracing revealed ventral respiratory column projections to prephrenic interneurons, suggesting that some propriospinal relays exist between medullary neurons and the phrenic nucleus. Dual-labeling studies with pseudorabies virus recombinants also showed prephrenic interneurons integrated with either contralateral phrenic or intercostal motoneuron pools. The stability of interneuronal pseudorabies virus labeling patterns following lateral cervical hemisection was then addressed. Except for fewer infected contralateral interneurons at the level of the central canal, the number and distribution of phrenic-associated interneurons was not significantly altered 2 weeks posthemisection (i.e., the point at which the earliest postinjury recovery of phrenic activity has been reported). These results demonstrate a heterogeneous population of phrenic-related interneurons. Their connectivity and relative stability after cervical hemisection raise speculation for potentially diverse roles in modulating phrenic function normally and postinjury.

The purpose of this study was to evaluate the abdominal CT findings in patients with spontaneous intramural small bowel haemorrhage. We retrospectively reviewed the abdominal CT scans of six patients with known intramural small bowel haemorrhage. All of the patients had an underlying coagulopathy. All six patients underwent CT examinations without oral or intravenous contrast media. All six non-contrast CT scans showed hyperattenuation of the involved bowel segments, with thickened and dilated proximal small bowel. Therefore, patients who are clinically at risk for intramural small bowel haemorrhage should undergo a non-contrast CT scan of the abdomen prior to the routine oral and intravenous contrast-enhanced scan. In most cases the non-contrast scan will provide definitive diagnostic information which may not be evident from the contrast-enhanced scan alone.

BACKGROUND Superinfection is an adverse event following smallpox vaccination. The clinical presentation is similar to that of a large normal vaccine reaction or "robust take," and the frequency is unknown. METHODS We retrospectively reviewed all reported severe local reactions consistent with superinfection among United States civilian smallpox vaccinees from January 2003 through January 2004. We applied a standard case definition and estimated the frequency of superinfection following smallpox vaccination. RESULTS We identified 48 reported cases for further review among 39,350 [corrected] smallpox vaccinees. Two (4%) of the 48 reported cases met the case definition for superinfection; neither of the patients had a pathogenic organism isolated from their infection site. Both were treated with antibiotics and resolved their infection. Of the 46 cases determined not to be superinfection, 41 (89%) were temporally consistent with a large normal vaccine reaction. Thirty (75%) of 40 reported case patients for whom data were available received antibiotic therapy. CONCLUSIONS Superinfection following smallpox vaccination is rare. Most of the reported superinfection cases were probably large normal smallpox vaccine reactions. Educating providers about the normal response to smallpox vaccine may decrease the overdiagnosis of superinfection and the unnecessary use of antimicrobials.

We evaluated the incidence and organ distribution of arterial extravasation identified using contrast-enhanced helical CT in patients who had sustained abdominal visceral injuries and pelvic fractures after blunt trauma.Five hundred sixty-five consecutive patients from four level I trauma centers who had CT scans showing abdominal visceral injuries or pelvic fractures were included in this series. The presence or absence of arterial extravasation, as well as the anatomic sites of arterial extravasation, was noted. We obtained clinical follow-up data, including surgical or angiographic findings.In our series, 104 (18.4%) of 565 patients had arterial extravasation. Of the 104 patients, 81 (77.9%) underwent surgery, embolization, or both. The combined rate of surgery or embolization in patients with arterial extravasation was statistically higher than expected at all four institutions (p0.001). The spleen was the most common organ injured, occurring in 277 (49.0%) of 565 patients, and arterial extravasation occurred in 49 (17.7%) of 277 patients with splenic injury. Several other visceral injuries were associated with arterial extravasation, including hepatic, renal, adrenal, and mesenteric injuries.Based on the limited reports of arterial extravasation in the nonhelical CT literature, the percentage (18%) of clinically stable patients in our study with CT scans showing arterial extravasation was higher than anticipated. This finding likely reflects the improved diagnostic capability of helical CT. Although the spleen and liver were the organs most commonly associated with arterial extravasation, radiologists should be aware that arterial extravasation may be associated with several other visceral injuries.

Objectives. To determine the incidence and spectrum of significant alternative or additional diagnoses established or suggested on unenhanced helical computed tomography (CT) in a large series of patients with suspected renal colic. Methods. One thousand consecutive unenhanced helical CT examinations were performed for suspected renal colic. All official CT reports were retrospectively reviewed, which was followed by review of all available relevant follow-up radiology reports. A selected image and chart review was also performed. Results. Ureteral calculi were identified on 557 examinations, findings consistent with a recently passed stone were discovered on 67 examinations, and 275 CT examinations were unremarkable. An alternative or additional diagnosis was established or suggested on 101 examinations, including in 26 patients with concurrent ureteral calculi. There were 62 genitourinary and 39 nongenitourinary tract diagnoses. Eighty-seven of the diagnoses could be confirmed on retrospective image review combined with patient follow-up. There were two false-positive diagnoses for significant, alternative pathologic findings. Conclusions. A wide spectrum of significant, alternative, and additional genitourinary and nongenitourinary diagnoses can be reliably established or suggested on unenhanced helical CT performed for suspected renal colic. These abnormalities were identified in 10% of cases in this series of 1000 consecutive CT examinations.

To determine the accuracy of helical computed tomography (CT) without the oral, intravenous, or rectal administration of contrast material in confirming suspected acute appendicitis.Three hundred consecutive patients referred from the departments of surgery and emergency medicine were examined for suspected acute appendicitis by using thin-section nonenhanced helical CT. All transverse CT scans were obtained in a single breath hold from the upper abdomen (T12 vertebra) to the pubic symphysis with 5-mm collimation and a pitch of 1.6. All scans were obtained without oral, intravenous, or rectal contrast material. Criteria for diagnosis of acute appendicitis included an enlarged appendix (6 mm) and periappendiceal inflammation. CT diagnoses were recorded prospectively. Final diagnoses were established with the results of surgical or clinical follow-up or both.There were 110 true-positive diagnoses, 181 true-negative diagnoses (63 of which were an alternative diagnosis correctly established prospectively), five false-negative diagnoses, and four false-positive diagnoses, which yielded a sensitivity of 96%, a specificity of 99%, and an accuracy of 97%.Nonenhanced helical CT is a highly accurate technique for diagnosing or excluding acute appendicitis. Developing experience with the technique and understanding the subtleties of interpretation can further improve diagnostic accuracy.

Unenhanced helical CT is an accurate technique for the evaluation of patients with suspected acute appendicitis. This non-operator-dependent examination can be performed without the risk of intravenous contrast material or the delay associated with the use of oral and rectal contrast material. This article reviews the unenhanced helical CT findings of acute appendicitis and those entities that commonly mimic acute appendicitis clinically.

The objective of our study was to determine the value of using color and power Doppler sonography to reveal extrathyroidal feeding arteries in the detection of abnormal parathyroid glands.Forty-four patients with primary hyperparathyroidism were imaged prospectively with high-resolution gray-scale, color flow, and power Doppler sonography. The presence of extrathyroidal arteries supplying the adenomas was noted. All patients underwent subsequent neck exploration. The locations of the abnormal glands were recorded.At surgery, 51 abnormal parathyroid glands were removed in the 44 patients. Sonography correctly revealed an adenoma in 40 of the 44 patients. Likewise, sonography revealed 42 of the 51 adenomas. Nine false-negative and two false-positive interpretations of the sonograms were made. Thus, overall sensitivity was 83%, specificity was 98%, and accuracy was 94%. Three of the false-negative interpretations were ectopic glands within the superior mediastinum. Excluding these three glands from analysis, the sensitivity for detection of adenomas within the neck was 88%, specificity was 98%, and accuracy was 95%. An extrathyroidal artery leading to a parathyroid adenoma was seen in 35 of the 42 adenomas revealed by sonography. The presence of an extrathyroidal artery leading to an adenoma was found to aid in the detection of an otherwise inconspicuous parathyroid gland in five patients, which improved sensitivity from 73% to 83%.Prominent vessels supplying parathyroid adenomas are frequently revealed by color flow and power Doppler sonography. These vessels can serve as "road maps" to abnormal parathyroid glands.

Although it is possible to diagnose primary high-grade thyroid lymphoma from a fine needle aspiration (FNA) biopsy, the distinction of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) from lymphocytic thyroiditis is sometimes problematic. Definitive diagnosis of lymphoma on cytologic specimens may be facilitated by the documentation of a clonal lymphoid proliferation within the specimen by flow cytometric immunophenotyping or immunocytochemistry. Recently, molecular techniques have also been developed to detect clonal lymphoid proliferation based on immunoglobulin (Ig) or T-cell receptor gene rearrangement. We have used a polymerase chain reaction (PCR)-based assay for Ig heavy chain gene arrangement to identify a clonal population of lymphocytes within the thyroid FNA specimen from a low-grade thyroid MALT lymphoma. Using this assay, we identified no distinct clonal population in five cytologic specimens of lymphocytic thyroiditis. Therefore, this PCR-based clonality assay represents a potentially useful adjunct to the cytologic diagnosis of thyroid lymphoma.

The objective of this study was to determine the incidence of urinary tract findings associated with ureteral stones on unenhanced helical CT scans of patients with acute renal colic.One hundred forty-one consecutive patients with suspected renal colic were referred by the emergency department for a helical CT scan that was obtained without oral or IV contrast. The CT scans of 54 of these patients were interpreted as positive for ureteral calculi, and these CT scans were reviewed retrospectively. The size and location of each ureteral calculus and of any concurrent urinary tract calculi were recorded. The presence or absence of hydronephrosis, hydroureter, perinephric edema or soft-tissue stranding, and periureteral edema was also noted.We reviewed the original 5-mm axial images from the 54 CT scans. Calculi were present in the proximal, mid, and distal ureter in eight, four, and 14 patients respectively, and at the ureterovesicular junction in 28 patients. Only two patients had more than one ureteral calculus, and none had a contralateral ureteral calculus. Concurrent renal parenchymal and/or nonobstructing calculi in the renal pelvis were seen in five patients with proximal, mid, or distal ureteral stones and in 16 patients with ureterovesicular junction stones. Hydronephrosis was found in 37 patients, hydroureter in 36 patients, and perinephric soft-tissue changes in 35 patients. Periureteral edema could not be evaluated in the 28 patients with ureterovesicular junction calculi because of the adjacent bladder, but periureteral edema was clearly seen immediately adjacent to the ureteral stone in 17 of the other 26 patients. Only two of the 54 patients had no evidence of hydronephrosis, hydroureter, or perinephric soft-tissue changes.In patients with ureteral calculi imaged with unenhanced CT for acute renal colic, associated findings included hydronephrosis, hydroureter, perinephric soft-tissue changes, and periureteral edema. These common findings provided supportive evidence that an acute obstructive process was present.

Expeditious diagnosis and treatment of pancreatic injury continues to elude the trauma surgeon and radiologist. Missed or underestimated pancreatic injury is responsible for a high level of morbidity and mortality after blunt or penetrating trauma. Unfortunately, inappropriate therapy can lead to devastating consequences such as severe endocrine or exocrine insufficiency. Abdominal CT is currently the imaging method of choice for evaluating patients with blunt trauma. This article reviews the constellation of CT findings that the radiologist must rely on to establish the diagnosis of pancreatic injury.

The purpose of this study was to determine the value of detecting fluid between the splenic vein and the pancreas on CT scans in the diagnosis of pancreatic injury after blunt abdominal trauma.We retrospectively reviewed the abdominal CT scans of 10 patients with surgical- or autopsy-proved pancreatic injury after blunt abdominal trauma. The finding of fluid interdigitating between the pancreas and the splenic vein was then studied along with the reported CT features of pancreatic injury. These included intraperitoneal fluid, fluid in the lesser sac, extraperitoneal fluid, pancreatic edema or hematoma, and thickening of the anterior renal fascia.The CT scans of all 10 patients reviewed showed abnormalities suggesting pancreatic injury. Only 40% of patients showed all of the findings reported in the literature. Fluid interdigitating between the splenic vein and the pancreatic parenchyma was seen on CT scans in 90%.Our experience suggests that fluid between the splenic vein and the pancreas is a helpful CT finding for the diagnosis of pancreatic injury after blunt abdominal trauma. This finding was easy to recognize and in the proper clinical setting directs attention to additional subtle findings of pancreatic injury.

Hypothesis High-resolution ultrasound and technetium Tc 99m sestamibi scanning can be used for preoperative localization of abnormal parathyroid glands in patients with hyperparathyroidism. Design Ultrasound and sestamibi scanning were performed in patients undergoing neck exploration for hyperparathyroidism. If the 2 scans agreed in identifying a single adenoma, and surgery confirmed the location of a single adenoma and an ipsilateral normal gland, a unilateral exploration was performed. Setting University tertiary care center. Patients Sixty-one consecutive patients undergoing surgery for hyperparathyroidism from September 1, 1994, through September 30, 1997. Interventions High-resolution ultrasound was performed in 59 patients and sestamibi scanning in 58 patients; all patients underwent neck exploration by a single surgeon. Main Outcome Measures The results of preoperative ultrasound and sestamibi scanning were compared with operative and histological findings. Results All patients were cured of hypercalcemia. Specificity of ultrasound and sestamibi scanning was 98% and 99%, respectively; however, their sensitivity was only 57% and 54%, respectively. Both imaging modalities had lower sensitivities in the setting of multigland disease. If both imaging studies were considered as a single test, sensitivity for imaging in patients with primary hyperparathyroidism reached 78%. Our localization protocol allowed a unilateral approach in 43% of patients (23 of 53). Conclusions These results confirm the value of preoperative localization in patients with hyperparathyroidism. A unilateral approach can be used with a high degree of success in cases when ultrasound and sestamibi scanning agree in the identification of a single adenoma confirmed by surgical exploration with the identification of a normal ipsilateral gland.