Thalamocortical Projections Are Significantly Impaired in the R6/2 Mouse Model of Huntington's Disease.

As Huntington's disease (HD) progresses, there is a significant loss of neurons in the striatum in addition to a distinct thinning of the cerebral cortex. Despite an early presence of sensorimotor deficits in patients with HD, electrophysiological studies designed to assess the integrity of thalamocortical circuits are sparse. Using the R6/2 mouse model of HD, we provide evidence of reduced connectivity between thalamic cells and their targeted cortical regions. Whole-cell patch clamp recordings from ventral anterolateral nucleus (VAL; motor) and ventral posteromedial nucleus (VPM; somatosensory) thalamic neurons in ex vivo brain slices of R6/2 and wild-type (WT) mice revealed that cells in both thalamic nuclei of R6/2 mice exhibited significant differences in passive and active cell membrane properties (smaller cell membrane capacitances, faster decay time constants and increased input resistances) compared with WT cells. Although only cells in the VPM of symptomatic R6/2 mice had more depolarized resting membrane potentials compared with WTs, cells in both nuclei displayed increased excitability in symptomatic, but not presymptomatic, R6/2 mice. Optical activation of VAL and VPM terminals elicited smaller magnitude current responses in cortical pyramidal neurons (CPNs) in both motor cortex (M1CTX) and somatosensory barrel cortex (BCTX) of symptomatic R6/2 mice compared with CPNs in WT mice. Furthermore, we observed a decrease in the frequency of thalamocortical excitatory quantal events in R6/2 BCTX CPNs, with no genotype-dependent differences in AMPA:NMDA response amplitude ratios. These data suggest there is a decrease in the transmission of thalamocortical information that is likely because of impaired neurotransmitter release.

CREB controls cortical circuit plasticity and functional recovery after stroke.

Treatments that stimulate neuronal excitability enhance motor performance after stroke. cAMP-response-element binding protein (CREB) is a transcription factor that plays a key role in neuronal excitability. Increasing the levels of CREB with a viral vector in a small pool of motor neurons enhances motor recovery after stroke, while blocking CREB signaling prevents stroke recovery. Silencing CREB-transfected neurons in the peri-infarct region with the hM4Di-DREADD blocks motor recovery. Reversing this inhibition allows recovery to continue, demonstrating that by manipulating the activity of CREB-transfected neurons it is possible to turn off and on stroke recovery. CREB transfection enhances remapping of injured somatosensory and motor circuits, and induces the formation of new connections within these circuits. CREB is a central molecular node in the circuit responses after stroke that lead to recovery from motor deficits.

Utility of barium studies for patients with recurrent weight gain after Roux-en-Y gastric bypass.

AIM: To determine the utility of barium studies for detecting abnormalities responsible for recurrent weight gain after gastric bypass surgery. METHODS: A computerized search identified 42 patients who had undergone barium studies for recurrent weight gain after gastric bypass and 42 controls. The images were reviewed to determine the frequency of staple-line breakdown and measure the length/width of the pouch and gastrojejunal anastomosis. A large pouch exceeded 6 cm in length or 5 cm in width and a wide anastomosis exceeded 2 cm. Records were reviewed for the amount of recurrent weight gain and subsequent weight loss after additional treatment. RESULTS: Staple-line breakdown was present in 6/42 patients (14%) with recurrent weight gain. When measurements were obtained, 13/35 patients (37%) with recurrent weight gain had a large pouch, three (9%) had a wide anastomosis, and four (11%) had both, whereas 22/42 controls (52%) had a large pouch, one (2%) had a wide anastomosis, and two (5%) had both. Ten patients (24%) with recurrent weight gain underwent staple-line repair (n = 3) or pouch/anastomosis revision (n = 7). These 10 patients had a mean weight loss of 38.1 lbs versus a mean loss of 8.6 lbs in 19 patients managed medically. CONCLUSION: Only 14% of patients with recurrent weight gain after gastric bypass had staple-line breakdown, whereas 57% had a large pouch, wide anastomosis, or both. Not all patients with abnormal anatomy had recurrent weight gain, but those who did were more likely to benefit from surgical intervention than from medical management.

Utility of chest CT for differentiating primary and secondary achalasia.

AIM: To determine the computed tomography (CT) findings of primary and secondary achalasia and to assess the utility of CT for differentiating these conditions. METHODS: A computerized search revealed 13 patients with primary achalasia and 15 with secondary achalasia who underwent chest CT during a 10-year period. The images were reviewed to determine whether there was distal oesophageal narrowing (including the length/contour of narrowing), oesophageal dilation, oesophageal wall thickening (including degree/symmetry/pattern of thickening), a soft-tissue mass at the gastro-oesophageal junction, mediastinal adenopathy, or other findings of malignant tumour. RESULTS: Eleven (85%) of 13 patients with primary achalasia had distal oesophageal narrowing at CT that was smooth in all patients; four (31%) had oesophageal wall thickening that was smooth and symmetric in all patients; none had a soft-tissue mass at the gastro-oesophageal junction or mediastinal lymphadenopathy; and two (15%) had pulmonary metastases from unrelated lung cancers. In contrast, 12 (80%) of 15 patients with secondary achalasia had distal oesophageal narrowing at CT; 11 (73%) had distal oesophageal wall thickening that was nodular/lobulate and asymmetric in seven (64%) and smooth and symmetric in four (36%); six (40%) had a soft-tissue mass at the gastro-oesophageal junction; seven (47%) had mediastinal lymphadenopathy; and all 15 had other findings of malignant tumour. CONCLUSION: CT is a useful technique for differentiating primary and secondary achalasia. Distal oesophageal wall thickening that is nodular/lobulate and asymmetric, a soft-tissue mass at the gastro-oesophageal junction, mediastinal lymphadenopathy, and pulmonary, hepatic, or osseous metastases are findings that favour secondary achalasia.

Pathophysiology of Huntington's disease: time-dependent alterations in synaptic and receptor function.

Huntington's disease (HD) is a progressive, fatal neurological condition caused by an expansion of CAG (glutamine) repeats in the coding region of the Huntington gene. To date, there is no cure but great strides have been made to understand pathophysiological mechanisms. In particular, genetic animal models of HD have been instrumental in elucidating the progression of behavioral and physiological alterations, which had not been possible using classic neurotoxin models. Our groups have pioneered the use of transgenic HD mice to examine the excitotoxicity hypothesis of striatal neuronal dysfunction and degeneration, as well as alterations in excitation and inhibition in striatum and cerebral cortex. In this review, we focus on synaptic and receptor alterations of striatal medium-sized spiny (MSNs) and cortical pyramidal neurons in genetic HD mouse models. We demonstrate a complex series of alterations that are region-specific and time-dependent. In particular, many changes are bidirectional depending on the degree of disease progression, that is, early vs. late, and also on the region examined. Early synaptic dysfunction is manifested by dysregulated glutamate release in striatum followed by progressive disconnection between cortex and striatum. The differential effects of altered glutamate release on MSNs originating the direct and indirect pathways is also elucidated, with the unexpected finding that cells of the direct striatal pathway are involved early in the course of the disease. In addition, we review evidence for early N-methyl-D-aspartate receptor (NMDAR) dysfunction leading to enhanced sensitivity of extrasynaptic receptors and a critical role of GluN2B subunits. Some of the alterations in late HD could be compensatory mechanisms designed to cope with early synaptic and receptor dysfunctions. The main findings indicate that HD treatments need to be designed according to the stage of disease progression and should consider regional differences.

Gastric bezoars: reassessment of clinical and radiographic findings in 19 patients.

The aim of this study was to reassess the clinical and radiographic findings in a series of patients with gastric bezoars. Radiology files revealed 19 patients with bezoars; 10 patients had CT and 10 had endoscopy before or after the barium studies. 11 patients (58%) had risk factors for gastroparesis and 6 (32%) had had previous gastric surgery, including 3 having had a gastric bypass or vertical banded gastroplasty. 18 patients (95%) had symptoms; in 10 of those patients, symptoms were present for 1 week or less (53%). On barium studies, the bezoars were round or ovoid in 17 patients (89%) and irregular in 2 (11%); mottled in 10 (53%) and homogeneous in 9 (47%); and mobile in 15 (79%) and immobile in 4 (21%). Gastroparesis was observed at fluoroscopy in 8 (62%) out of 13 patients without gastric surgery. Symptoms improved/resolved in 12 (67%) out of 18 patients. Follow-up CT or endoscopy showed resolution of the bezoars in 8 (80%) out of 10 patients; the mean interval to resolution was 12 days. Our experience suggests that gastroparesis is the single most common cause of bezoars, accounting for the majority of cases. Partial gastric resection or bariatric surgery should also be recognized as a cause of bezoar formation. These lesions may be manifested on barium studies by a spectrum of findings, appearing as mottled or homogeneous, mobile or immobile masses, sometimes filling the gastric pouch after bariatric surgery. Affected individuals often have an acute clinical presentation with symptoms for 1 week or less, and some bezoars resolve rapidly on conservative medical treatment.

Alterations in corticostriatal synaptic plasticity in mice overexpressing human alpha-synuclein.

Most forms of Parkinson's disease (PD) are sporadic in nature, but some have genetic causes as first described for the alpha-synuclein gene. The alpha-synuclein protein also accumulates as insoluble aggregates in Lewy bodies in sporadic PD as well as in most inherited forms of PD. The focus of the present study is the modulation of synaptic plasticity in the corticostriatal pathway of transgenic (Tg) mice that overexpress the human alpha-synuclein protein throughout the brain (ASOTg). Paired-pulse facilitation was detected in vitro by activation of corticostriatal afferents in ASOTg mice, consistent with a presynaptic effect of elevated human alpha-synuclein. However basal synaptic transmission was unchanged in ASOTg, suggesting that human alpha-synuclein could impact paired-pulse facilitation via a presynaptic mechanism not directly related to the probability of neurotransmitter release. Mice lacking alpha-synuclein or those expressing normal and A53T human alpha-synuclein in tyrosine hydroxylase-containing neurons showed, instead, paired-pulse depression. High-frequency stimulation induced a presynaptic form of long-term depression solely in ASOTg striatum. A presynaptic, N-methyl-d-aspartate receptor-independent form of chemical long-term potentiation induced by forskolin (FSK) was enhanced in ASOTg striatum, while FSK-induced cAMP levels were reduced in ASOTg synaptoneurosome fractions. Overall the results suggest that elevated human alpha-synuclein alters presynaptic plasticity in the corticostriatal pathway, possibly reflecting a reduction in glutamate at corticostriatal synapses by modulation of adenylyl cyclase signaling pathways. ASOTg mice may recapitulate an early stage in PD during which overexpressed alpha-synuclein dampens corticostriatal synaptic transmission and reduces movement.

Extensive early motor and non-motor behavioral deficits are followed by striatal neuronal loss in knock-in Huntington's disease mice.

Huntington's disease is a neurodegenerative disorder, caused by an elongation of CAG repeats in the huntingtin gene. Mice with an insertion of an expanded polyglutamine repeat in the mouse huntingtin gene (knock-in mice) most closely model the disease because the mutation is expressed in the proper genomic and protein context. However, few knock-in mouse lines have been extensively characterized and available data suggest marked differences in the extent and time course of their behavioral and pathological phenotype. We have previously described behavioral anomalies in the open field as early as 1 month of age, followed by the appearance at 2 months of progressive huntingtin neuropathology, in a mouse carrying a portion of human exon 1 with approximately 140 CAG repeats inserted into the mouse huntingtin gene. Here we extend these observations by showing that early behavioral anomalies exist in a wide range of motor (climbing, vertical pole, rotarod, and running wheel performance) and non-motor functions (fear conditioning and anxiety) starting at 1-4 months of age, and are followed by progressive gliosis and decrease in dopamine and cyclic AMP-regulated phosphoprotein with molecular weight 32 kDa (DARPP32) (12 months) and a loss of striatal neurons at 2 years. At this age, mice also present striking spontaneous behavioral deficits in their home cage. The data show that this line of knock-in mice reproduces canonical characteristics of Huntington's disease, preceded by deficits which may correspond to the protracted pre-manifest phase of the disease in humans. Accordingly, they provide a useful model to elucidate early mechanisms of pathophysiology and the progression to overt neurodegeneration.

An 8-year review of barium studies in the diagnosis of gastroparesis.

AIM: To determine the utility of barium studies for diagnosing gastroparesis in patients with nausea, vomiting, or other related symptoms. MATERIALS AND METHODS: Radiology files revealed gastroparesis without gastric outlet obstruction on upper gastrointestinal tract barium studies in 50 patients with nausea, vomiting, and other related symptoms. Original reports and images were reviewed to determine whether gastric peristalsis was decreased/absent and to investigate gastric dilatation, fluid or debris, and delayed emptying of barium. Twenty patients (40%) had nuclear gastric emptying studies. Medical records were reviewed to determine the presentation, treatment, and course. The diagnosis of gastroparesis was considered accurate if patients with gastroparesis on barium studies responded to treatment. RESULTS: Forty-six patients (92%) had predisposing factors for gastroparesis, including narcotics and diabetes. Forty-five patients (90%) presented with nausea or vomiting, and 40 patients (80%) had one or more other symptoms, including bloating, early satiety, postprandial fullness, and abdominal pain. Barium studies revealed decreased gastric peristalsis in 46 (92%) of the 50 patients and absent peristalsis in four (8%); 46 patients (92%) had additional findings, including gastric dilatation in 30 (60%), delayed emptying of barium in 27 (54%), debris in 28 (56%; bezoars in three), and retained fluid in 13 (26%). Thirteen (65%) of 20 patients with nuclear gastric emptying studies had delayed emptying of solids and seven (35%) had normal emptying. Thirty-five (83%) of 42 patients treated for gastroparesis had symptomatic improvement versus two (25%) of eight patients not treated. CONCLUSION: Patients with nausea, vomiting, or other related symptoms who have gastroparesis without gastric outlet obstruction on barium studies can be treated for this condition on the basis of the clinical and radiographic findings.

Behavioral effects of dopaminergic agonists in transgenic mice overexpressing human wildtype alpha-synuclein.

Overexpression of alpha-synuclein causes familial Parkinson's disease and abnormal aggregates of the protein are present in sporadic cases of the disease. We have examined the behavioral effects of direct and indirect dopaminergic agonists in transgenic mice expressing human alpha-synuclein under the Thy-1 promoter (Thy1-aSyn, alpha-synuclein overexpressor), which exhibit progressive impairments in behavioral tests sensitive to nigrostriatal dopamine dysfunction. Male Thy1-aSyn and wild-type mice received vehicle, benserazide/L-DOPA (25 mg/kg, i.p.), high (2 mg/kg, s.c.) and low doses (0.125, 0.25, 0.5 mg/kg, s.c.) of apomorphine, and amphetamine (5 mg/kg, i.p.), beginning at 3 months of age, and were tested on the challenging beam, spontaneous activity, pole test, and gait. l-DOPA had a paradoxical effect and worsened the deficits in Thy1-aSyn mice compared with controls, whereas the high dose of apomorphine only produced few deficits above those already present in Thy1-aSyn. In contrast to wild-type mice, Thy1-aSyn mice did not show amphetamine-induced stereotypies. The results indicate that chronic overexpression of alpha-synuclein led to abnormal pharmacological responses in mice.

Early behavioral deficits in R6/2 mice suitable for use in preclinical drug testing.

Huntington's disease (HD) is a neurodegenerative disorder caused by an elongated glutamine repeat in huntingtin. Improved understanding of the molecular effects of the mutation opens new avenues for treatment. High-throughput automated behavioral tests that produce well-defined markers of disease progression are necessary for in vivo drug screening. We have identified early behavioral deficits in tests of motor function that are amenable to cost effective automated analysis in a mouse model of HD. Running wheel activity and climbing behavior were reduced in R6/2 HD transgenics from as early as 4.5 weeks of age, at a time when rotarod performance and grip strength were still normal. Power calculations showed that the running wheel test was appropriate for efficient, high-throughput drug screening at this early age. Furthermore, the data extend the range of behavioral deficits observed in 1-month-old R6/2 mice, an age when synaptic dysfunction can already be detected in the striatum.

Pediatric cortical dysplasia: correlations between neuroimaging, electrophysiology and location of cytomegalic neurons and balloon cells and glutamate/GABA synaptic circuits.

Seizures in cortical dysplasia (CD) could be from cytomegalic neurons and balloon cells acting as epileptic 'pacemakers', or abnormal neurotransmission. This study examined these hypotheses using in vitro electrophysiological techniques to determine intrinsic membrane properties and spontaneous glutamatergic and GABAergic synaptic activity for normal-pyramidal neurons, cytomegalic neurons and balloon cells from 67 neocortical sites originating from 43 CD patients (ages 0.2-14 years). Magnetic resonance imaging (MRI), (18)fluoro-2-deoxyglucose positron emission tomography (FDG-PET) and electrocorticography graded cortical sample sites from least to worst CD abnormality. Results found that cytomegalic neurons and balloon cells were observed more frequently in areas of severe CD compared with mild or normal CD regions as assessed by FDG-PET/MRI. Cytomegalic neurons (but not balloon cells) correlated with the worst electrocorticography scores. Electrophysiological recordings demonstrated that cytomegalic and normal-pyramidal neurons displayed similar firing properties without intrinsic bursting. By contrast, balloon cells were electrically silent. Normal-pyramidal and cytomegalic neurons displayed decreased spontaneous glutamatergic synaptic activity in areas of severe FDG-PET/MRI abnormalities compared with normal regions, while GABAergic activity was unaltered. In CD, these findings indicate that cytomegalic neurons (but not balloon cells) might contribute to epileptogenesis, but are not likely to be 'pacemaker' cells capable of spontaneous paroxysmal depolarizations. Furthermore, there was more GABA relative to glutamate synaptic neurotransmission in areas of severe CD. Thus, in CD tissue alternate mechanisms of epileptogenesis should be considered, and we suggest that GABAergic synaptic circuits interacting with cytomegalic and normal-pyramidal neurons with immature receptor properties might contribute to seizure generation.

Transient failure of opening of the lower oesophageal sphincter on upright oesophagrams: radiographic and clinical findings.

The purpose of our study was to determine the frequency, radiographic features, and clinical importance of transient failure of opening of the lower oesophageal sphincter (LOS) on upright double-contrast views of the oesophagus. A computerized search of radiology records identified 16 patients who had transient failure of opening of the LOS on upright views from biphasic oesophagrams or upper gastrointestinal tract examinations using high-density barium but normal opening of the LOS on prone views using low-density barium. The radiographic findings were reviewed and correlated with the clinical and manometric findings. In all cases, barium studies revealed tapered, beaklike narrowing of the distal oesophagus on upright double-contrast views, with a normal-appearing distal oesophagus, normal opening of the LOS, and intact peristalsis on prone single-contrast views. Only seven patients (44%) had dysphagia. Five of these patients had clinical follow-up, and the dysphagia improved or resolved without specific treatment for LOS dysfunction in four. The remaining patient had persistent dysphagia, but this individual had polymyositis as the likely cause for his dysphagia. Manometry revealed incomplete relaxation of the LOS in two patients and normal relaxation in one. Our experience suggests that failure of opening of the LOS may be observed as a transient finding of little clinical importance on upright double-contrast views of the oesophagus using high-density barium, with normal opening of the LOS on prone single-contrast views using low-density barium. It is important to be aware of this finding, so that it is not mistaken for achalasia or other abnormalities of the distal oesophagus.

Gastritis from NSAIDS to Helicobacter pylori.

Gastritis is a histologic diagnosis. To understand gastritis, the radiologist must have some working knowledge of gastric histology and pathology. Therefore, this article first describes normal histologic and radiologic anatomy. The pathology of gastritis is then presented to give the radiologist a basis for understanding the radiologic findings. Finally, gastritis is discussed from a clinical and radiologic perspective.

Barrett esophagus: update for radiologists.

Barrett esophagus is a well-recognized entity in which there is progressive columnar metaplasia of the lower esophagus due to longstanding gastroesophageal reflux and reflux esophagitis [1]. This condition is important because it is associated with an increased risk of developing esophageal adenocarcinoma by a well-established sequence from dysplasia to carcinoma [2]. During the past decade, however, an explosion of new data has dramatically affected our understanding of Barrett esophagus. Not only have revised histopathologic criteria been developed for this condition, but it is currently believed that patients with Barrett esophagus should be classified as having "short-segment" or "long-segment" disease based on the extent of columnar metaplasia in the distal esophagus. This distinction has important implications for the risk of developing esophageal adenocarcinoma and subsequent need for endoscopic surveillance. The purpose of this article is to present these new concepts about Barrett esophagus and provide radiologists with a more current framework for diagnosing this condition.

Laparoscopic Heller myotomy and fundoplication: findings and predictive value of early postoperative radiographic studies.

BACKGROUND: We describe the findings on esophagography, the frequency and appearance of leaks after laparoscopic Heller myotomy and fundoplication, and the utility of early postoperative studies for predicting clinical outcome. METHODS: Our study group consisted of 40 patients who underwent laparoscopic Heller myotomy and fundoplication in whom radiographic studies were performed during the early postoperative period. The radiographic reports and images were reviewed to determine the esophageal diameter, visualization or nonvisualization of the wrap, and the presence or absence of a leak. The esophageal diameter subsequently was correlated with the clinical findings to determine whether this was a useful parameter for predicting clinical outcome. RESULTS: Two patients (5%) had small, sealed-off leaks on radiographic studies, and four (10%) had pseudo-leaks resulting from trapping of contrast material alongside the fundoplication wrap. Twelve (60%) of 20 patients with a dilated esophagus had esophageal symptoms on short-term follow-up versus three (15%) of 20 with a normal-caliber esophagus (p = 0.008), and five (56%) of nine patients with a dilated esophagus had symptoms on long-term follow-up versus six (43%) of 14 with a normal-caliber esophagus (p = 0.68). CONCLUSION: Radiographic studies are useful for showing leaks after laparoscopic Heller myotomy and fundoplication, but radiologists should differentiate true leaks from trapping of contrast material alongside the fundoplication wrap. The caliber of the esophagus on early postoperative studies is also a useful parameter for predicting short-term clinical outcome in these patients.

Calcium modulates dopamine potentiation of N-methyl-D-aspartate responses: electrophysiological and imaging evidence.

In the striatum, dopamine (DA) exerts a major modulatory influence on voltage- and ligand-gated currents. Previously we have shown that DA modulates glutamatergic neurotransmission and that the direction of this modulation depends on, among other factors, the glutamate and DA receptor subtypes activated. These effects also involve DA-induced alterations in voltage-gated Ca(2+) currents. In the present experiments, the effects of Ca(2+) channel blockers on DA and D1 receptor-dependent potentiation of N-methyl-D-aspartate (NMDA) responses were examined in vitro in striatal slices using current clamp recording techniques. DA or D1 receptor agonists consistently enhanced NMDA responses. Cadmium and the more selective L-type Ca(2+) channel antagonists nifedipine and methoxyverapamil reduced the potentiation of NMDA responses by DA or D1 receptor activation. Furthermore, studies using Ca(2+) imaging with Fluo-3 in cultured cortical or dissociated striatal neurons demonstrated that DA and D1 agonists increased intracellular Ca(2+) transients induced by NMDA. These as well as previous findings indicate that in striatal neurons at least two mechanisms contribute to the enhancement of NMDA responses by DA receptor activation, facilitation of voltage-gated Ca(2+) currents and D1 receptor activation of the cAMP-protein kinase A cascade. The existence of multiple mechanisms leading to a similar outcome allows a certain degree of redundancy in the consequences of DA modulation.

Endogenous opioids mediate basal hedonic tone independent of dopamine D-1 or D-2 receptor activation.

Exogenously administered opiates are recognized as rewarding and the involvement of dopamine systems in mediating their apparent pleasurable effects is contentious. The aversive response to naloxone administration observed in animal studies suggests the presence of an endogenous opioid tone regulating hedonic state. We sought evidence for the requirement for dopamine systems in mediating this action of endogenous opioids by determining whether mice deficient in dopamine D-1 or D-2 receptors were able to display conditioned place aversion to naloxone. Mice received saline in the morning in one chamber and either saline or naloxone (10 mg/kg, s.c.) in the afternoon in another chamber, each day for 3 days. On the test day they were given free access to the testing chambers in the afternoon. Similar to their wild-type littermates, D-1 and D-2 receptor knockout mice receiving naloxone in the afternoon spent significantly less time on the test day in the compartment in which they previously received naloxone, compared with animals receiving saline in the afternoon. The persistence of naloxone-conditioned place aversion in D-1 and D-2 knockout mice suggests that endogenous opioid peptides maintain a basal level of positive affect that is not dependent on downstream activation of dopamine systems involving D-1 or D-2 receptors.

Detection of reflux esophagitis on double-contrast esophagrams and endoscopy using the histologic findings as the gold standard.

The purpose of our study was to determine the accuracy of double-contrast barium studies and endoscopy for detecting reflux esophagitis, using the endoscopic biopsy findings as the gold standard. A review of radiology, endoscopy, and pathology files showed 37 patients with reflux symptoms who underwent double-contrast barium studies and endoscopy with biopsy specimens from the esophagus. The radiographic images were reviewed in a blinded fashion and correlated with the endoscopic and histologic findings to determine the radiographic and endoscopic accuracies for detecting reflux esophagitis, using the endoscopic biopsy specimens as the gold standard. Double-contrast barium studies and endoscopy had low but comparable accuracies for detecting reflux esophagitis, with sensitivities of 35% and 39%, specificities of 79% and 71%, positive predictive values of 73% and 69%, and negative predictive values of 42% and 41%, respectively. When mucosa granularity was evaluated as an individual sign of esophagitis on double-contrast studies, this finding had a sensitivity of 35%, a specificity of 93%, a positive predictive value of 89%, and a negative predictive value of 46% for detecting reflux esophagitis. Our experience suggests that double-contrast barium studies and endoscopy have limited ability to detect reflux esophagitis, in particular mild esophagitis, when using the histologic findings as the gold standard. When radiographic abnormalities are detected, however, mucosal granularity is the single best sign of reflux esophagitis on double-contrast studies.