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Introduction: Cells containing GIP and CCK predominate in the upper small intestine, while those containing GLP-1 are located more distally. Our aim was to compare the hormonal, glycemic and appetite responses to different sites of glucose delivery.Methods: Ten healthy males were each studied twice, in randomized order. A catheter was positioned with openings 15 cm beyond the pylorus (“duodenal”), and 100 cm beyond (“mid-jejunal”). On one day, glucose was infused into the duodenum (1 kcal/min) and saline into the mid-jejunum, for 90 min. On the other day,the infusion sites were reversed. Blood was sampled frequently, and hunger was scored by questionnaires. The tube was removed and energy intake measured from a buffet meal. Results: Stimulation of CCK and suppression of hunger were greater (each Pb0.05), and energy intake less (P=0.05), with duodenal compared to mid-jejunal glucose infusion. Blood glucose, GIP, and insulin did not differ, and there was minimal GLP-1 increment on either day.Conclusions: There is regional variation in CCK, but not incretin hormone release, in the upper small intestine,and modest differences in the site of glucose exposure affect appetite and energy intake. Refereed/Peer-reviewed

It is unknown how the interdigestive migrating motor complex influences the gastric emptying of liquids. Therefore, the gastric emptying rate of 50- and 200-mL volumes of phenol red solution were measured while monitoring contractile activity. Motor activity was recorded using a hydraulic manometric system and expressed as either the proximity of dosing time to time of appearance of phase III or as a motility index, defined as (contractile area)/(sampling interval time). After an initial lag period, emptying was log linear. With a 50-mL oral dose, the mean gastric emptying rate of the log-linear phase was successively faster during phase I (0.018 +/- 0.003 min-1), phase II (0.083 +/- 0.031 min-1), and late phase II/III (0.171 +/- 0.066 min-1) (P less than 0.05). Similarly, the mean lag time decreased successively with phases I, II, and late II/III (19.1 +/- 12.4, 7.6 +/- 5.6, and 3.8 +/- 2.8 minutes, respectively). At a 200-mL oral dose, there was no difference in the emptying rate between phase I and phase II (0.104 +/- 0.0014 vs. 0.110 +/- 0.041 min-1), but the emptying rate during late phase II/III was significantly greater (0.236 +/- 0.069 min-1); lag time was not dependent on phase. There was a statistical difference in the overall mean emptying rate between the 50- and 200-mL volumes. Also, during phase I, the emptying rate was faster for the 200-mL volume. This study shows a strong dependence of liquid gastric emptying rate and lag time on interdigestive antral motility, the emptying of small volumes being more dependent on motility phase than that of large volumes. Phase-related fluctuations in contractile activity can account for much of the reported variability in gastric emptying data. Furthermore, this study suggests that dose volume and interdigestive motor activity at the time of drug administration can affect absorption and onset of therapeutic response for some drugs.

This report is from the second workshop held in Washington DC on controlled/modified release dosage forms. The objectives were to determine the optimum information needed to characterize the drug entity and the drug dosage form, to explore the in vitro-in vivo relationship so as to determine the criteria for establishing an in vitro-in vivo correlation as well as the usefulness of in vitro data in the drug approval/regulatory process.

Both load and duration of small intestinal lipid infusion affect antropyloroduodenal motility and CCK and peptide YY (PYY) release at loads comparable to and higher than the normal gastric emptying rate. We determined 1) the effects of intraduodenal lipid loads well below the mean rate of gastric emptying on, and 2) the relationships between antropyloroduodenal motility, CCK, PYY, appetite, and energy intake. Sixteen healthy males were studied on four occasions in double-blind, randomized fashion. Antropyloroduodenal motility, plasma CCK and PYY, and appetite perceptions were measured during 50-min IL (Intralipid) infusions at: 0.25 (IL0.25), 1.5 (IL1.5), and 4 (IL4) kcal/min or saline (control), after which energy intake at a buffet meal was quantified. IL0.25 stimulated isolated pyloric pressure waves (PWs) and CCK release, albeit transiently, and suppressed antral PWs, PW sequences, and hunger ( P < 0.05) but had no effect on basal pyloric pressure or PYY when compared with control. Loads ≥ 1.5 kcal/min were required for the stimulation of basal pyloric pressures and PYY and suppression of duodenal PWs ( P < 0.05). All of these effects were related to the lipid load ( R > 0.5 or < −0.5, P < 0.05). Only IL4 reduced energy intake (in kcal: control, 1,289 ± 62; IL0.25, 1,282 ± 44; IL1.5, 1,235 ± 71; and IL4, 1,139 ± 65 compared with control and IL0.25, P < 0.05). In conclusion, in healthy males the effects of intraduodenal lipid on antropyloroduodenal motility, plasma CCK and PYY, appetite, and energy intake are load dependent, and the threshold loads required to elicit responses vary for these parameters.

This is a double-blind placebo-controlled study of sustained-release bupropion as a smoking cessation aid in alcoholics undergoing treatment for their alcoholism. Participants ( N =58) were enrolled within 1 week of entry into alcohol treatment from community and Veterans Affairs Substance Use Disorder programs. All participants received nicotine patch and were invited to attend a smoking cessation lecture and group. Cigarette smoking and alcohol outcomes were measured at 6 months. Bupropion when added to nicotine patch did not improve smoking outcomes. One third of participants on bupropion reported discontinuing the drug during weeks 1–4. Participants reported cigarette outcomes with nicotine patch that are similar to those seen in the general population. All study participants significantly reduced cigarette use. Comorbid affective disorder or antipersonality disorder did not affect outcomes. Alcohol outcomes were improved in those who discontinued cigarettes.

The "incretin" hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), account for some 60% of the stimulation of insulin by oral glucose, but the determinants of their secretion from the small intestine are poorly understood. Cells which release GIP (K cells) are localized to the proximal small intestine, while GLP-1 releasing cells (L cells) predominate in the distal gut. It has been suggested that a threshold rate of duodenal glucose delivery (approximately 1.8 kcal/min) needs to be exceeded for stimulation of GLP-1.To determine whether a low intraduodenal glucose load (1 kcal/min) has the capacity to stimulate GLP-1, and if so, the characteristics of the response.Retrospective analysis of all studies in our laboratory involving healthy humans administered intraduodenal glucose at 1 kcal/min for 120 min.Clinical research laboratory.27 healthy subjects (24 male; age 36+/-3 years; BMI 25.2+/-0.7 kg/m(2)).Plasma GLP-1, GIP, insulin, and blood glucose concentrations, reported as mean+/-SEM.During intraduodenal glucose, plasma GLP-1 increased at 15 and 30 min (P0.001 for both) and returned to baseline thereafter. In contrast, there were sustained increases in plasma GIP (P0.001), insulin (P0.001), and blood glucose (P0.001).In healthy subjects, there is early, transient stimulation of GLP-1 by glucose loads hitherto believed to be "sub-threshold". The mechanisms underlying this effect, which could be attributed to initially rapid transit to jejunal L cells, or a duodeno-jejunoileal neural or hormonal loop, remain to be determined.

Summary Objective To evaluate the relationship between neck abscess characteristics on computerized tomography (CT) scan and surgical drainage in pediatric patients. Methods Retrospective data warehouse review identified 43 children younger than 19 years admitted to a tertiary care pediatric hospital during the first quarters of 2000 through 2003 who underwent CT imaging for suspicion of head and neck abscesses involving the neck; face; and peritonsillar, retropharyngeal, and parapharyngeal spaces. A total of 45 scans were graded by a radiologist blinded to management. Thickness of the prevertebral soft tissue; location, dimensions, and degree of enhancement of the abscess; patient age; steroid and preadmission antibiotic use; and surgical intervention were recorded. Results Surgical drainage was performed in 32 of 43 patients (74%). We found no significant correlation between prevertebral soft tissue thickness, abscess dimensions or enhancement on CT scan, and surgical drainage. There was no significant association between surgical drainage and patient age, administration of steroids, or preadmission antibiotic use. Conclusions Neck abscess appearance on CT scan did not predict surgical drainage, although prevertebral soft tissue thickness and abscess dimensions may be important features. Abscess enhancement, patient age, and the use of steroids and prehospitalization antibiotics were not found to correlate with surgical drainage.

Methamphetamine use has been characterized as a “rural” drug; however, little is known about rural methamphetamine use disorders (MUD). This study describes and compares characteristics of rural and urban patients with MUD. Rural study participants reported earlier first regular use of methamphetamine, more alcoholism, more intravenous use, and a greater number of cigarettes/day, and were more likely to report methamphetamine-related psychotic symptoms. Rural methamphetamine users report multiple factors that may contribute to medical and psychiatric complications and worsen their prognosis. This is of significant concern given the limited substance abuse, mental health, and specialty care available in most rural Midwestern communities. (Am J Addict 2007;16:79–84)

Animal studies suggest that the effects of fatty acids on gastric emptying and pancreatic secretion are both concentration and load dependent, while their suppressive effect on energy intake is only load dependent. We postulated that, in humans, the modulation of antropyloroduodenal pressure waves, plasma cholecystokinin (CCK) and peptide YY (PYY) concentrations and energy intake by intraduodenal lauric acid, a fatty acid with 12 carbon atoms (‘C12’) would be load, but not concentration, dependent. Two groups of 12 healthy males were each studied on three separate occasions in double-blind randomized fashion. Antropyloroduodenal pressure waves, plasma CCK and PYY, and appetite perceptions were measured during intraduodenal infusions of C12 at (1) different loads of (i) 0.2, (ii) 0.3 and (iii) 0.4 kcal min−1 (all 56 mm) for 90 min, and (2) different concentrations of (i) 40, (ii) 56 and (iii) 72 mm (all 0.4 kcal min−1) for 60 min. Energy intake at a buffet meal consumed immediately following each infusion was quantified. Suppression of antral and duodenal pressure waves, stimulation of pyloric pressure waves, stimulation of plasma CCK and PYY, and suppression of energy intake, were related to the load of C12 administered (r > 0.65, P < 0.05). In contrast, there were no concentration-dependent effects of C12 on any of these parameters. In conclusion, in humans, the effects of intraduodenal C12 on antropyloroduodenal motility, plasma CCK and PYY and energy intake appear to be related to load, but not concentration, at least at the loads and concentrations evaluated.

Trends of urology workforce, subspecialization, recruitment practices, retirement planning, practice characteristics and managed care impacts in the United States were assessed.In February 1996 the executive interviewing branch of The Gallup Organization selected randomly and interviewed by telephone 507 practicing urologists in the United States who had provided urological patient care for more than 20 hours per week, practiced in 1995 and completed a urological residency program.Several important issues emerged. Urologists think we may be training too many urologists, subspecialty board certification would be a divisive issue to urology as a whole and 90% of urologists have an active retirement plan, although 23% are not funding the plan fully.The American Urological Association Gallup Poll, as refined by the Health Policy Survey and Research Committee, continues to be a unique and valuable tool in assessing practice patterns, gathering demographic data and measuring opinions of the American urologist. This information will help us chart our way to the twenty-first century.

We have investigated the effects of exogenous CCK-8 and GLP-1, alone and in combination, on ghrelin and PYY secretion. Nine healthy males were studied on four occasions. Plasma ghrelin and PYY concentrations were measured during 150 min intravenous infusions of: (i) isotonic saline, (ii) CCK-8 at 1.8 pmol/kg/min, (iii) GLP-1 at 0.9 pmol/kg/min or (iv) CCK-8 and GLP-1 combined. CCK-8 markedly suppressed ghrelin and stimulated PYY when compared with control between t=0-120 min (P0.001 for both). GLP-1 had no effect on ghrelin, but decreased PYY slightly at 120 min (P0.05). During infusion of CCK-8+GLP-1, there was comparable suppression of ghrelin (P0.001), but the stimulation of PYY was less (P0.001), than that induced by CCK-8, between t=20-120 min. In conclusion, in healthy subjects, in the doses evaluated, exogenous CCK-8 suppresses ghrelin and stimulates PYY, and exogenous GLP-1 has no effect on ghrelin and attenuates the effect of CCK-8 on PYY.

Previous observations suggest that glucagon-like peptide-1 (GLP-1) is released into the bloodstream only when dietary carbohydrate enters the duodenum at rates that exceed the absorptive capacity of the proximal small intestine to contact GLP-1 bearing mucosa in more distal bowel. The aims of this study were to determine the effects of modifying the length of small intestine exposed to glucose on plasma concentrations of GLP-1 and also glucose-dependent insulinotropic peptide (GIP), insulin, cholecystokinin (CCK) and ghrelin, and antropyloric pressures. Glucose was infused at 3.5 kcal/min into the duodenum of eight healthy males (age 18–59 yr) over 60 min on the first day into an isolated 60-cm segment of the proximal small intestine (“short-segment infusion”); on the second day, the same amount of glucose was infused with access to the entire small intestine (“long-segment infusion”). Plasma GLP-1 increased and ghrelin decreased ( P < 0.05 for both) during the long-, but not the short-, segment infusion. By contrast, increases in plasma CCK and GIP did not differ between days. The rises in blood glucose and plasma insulin were greater during the long- than during the short-segment infusion ( P < 0.05). During the long- but not the short-segment infusion, antral pressure waves (PWs) were suppressed ( P < 0.05). Isolated pyloric PWs and basal pyloric pressure were stimulated on both days. In conclusion, the release of GLP-1 and ghrelin, but not CCK and GIP, is dependent upon >60 cm of the intestine being exposed to glucose.

Postprandial hypotension (PPH) occurs frequently in the elderly; the magnitude of the fall in blood pressure (BP) is related to the rate of glucose entry into the duodenum during intraduodenal glucose infusion and spontaneous gastric emptying (GE). It is unclear if glucose concentration affects the hypotensive response. Gastric distension may attenuate PPH; therefore, meal volume could influence the BP response. We aimed to determine the effects of 1) drink volume, 2) glucose concentration, and 3) glucose content on the BP and heart rate (HR) responses to oral glucose. Ten subjects (73.9 ± 1.2 yr) had measurements of BP, GE, and blood glucose on 4 days after 1) 25 g glucose in 200 ml (12.5%), 2) 75 g glucose in 200 ml (37.5%), 3) 25 g glucose in 600 ml (4%), and 4) 75 g glucose in 600 ml (12.5%). GE, BP, HR, and blood glucose were measured for 180 min. After all drinks, duodenal glucose loads were similar in the first 60 min. Regardless of concentration, 600-ml (but not 200-ml) drinks initially increased BP, and in the first 30 min, systolic BP correlated ( P < 0.01) with volume in both the proximal and total stomach. At the same concentration (12.5%), systolic BP fell more ( P = 0.02) at the smaller volume; at the same volumes, there were no effects of concentration on BP. There was no difference in the glycemic response to drinks of identical glucose content. We conclude that 1) ingestion of glucose at a higher volume attenuates and 2) under constant duodenal load, glucose concentration (4–37%) does not affect the fall in BP.

The aims of this study were to determine whether the hypotensive and heart rate responses to small intestinal glucose infusion are dependent on the glucose concentration. Eight healthy subjects, aged 65–78 years, were studied on 3 separate days in random order. Each subject received intraduodenal infusions of 50 g of glucose in either 300 mL (16.7%), 600 mL (8.3%), or 1200 mL (4.1%) of saline (0.9%) at a rate of 3 kcal/min for 60 minutes (t = 0–60 minutes), followed by saline (0.9%) for a further 60 minutes (t = 60–120 minutes). During the infusions, blood pressure (systolic and diastolic) and heart rate were measured every 3 minutes, and blood glucose concentrations every 15 minutes. Systolic and diastolic blood pressure fell (P < .0001), and heart rate and blood glucose increased (P = .0001 for both) over time, during all 3 infusions. Between t = −2–120 minutes, there was no difference in systolic blood pressure (P = .20), diastolic blood pressure (P = .61), or heart rate (P = .09) over the study days. There was also no significant difference in the glycemic response to the infusions. We conclude that in healthy older subjects, glucose concentration does not affect the blood pressure or heart rate responses to intraduodenal glucose and that, therefore, the magnitude of the postprandial fall in blood pressure induced by oral glucose is likely to depend primarily on the small intestinal glucose load.

The gastrointestinal effects of intraluminal fats may be critically dependent on the chain length of fatty acids released during lipolysis. We postulated that intraduodenal administration of lauric acid (12 carbon atoms; C12) would suppress appetite, modulate antropyloroduodenal pressure waves (PWs), and stimulate the release of cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) more than an identical dose of decanoic acid (10 carbon atoms; C10). Eight healthy males (19–47 yr old) were studied on three occasions in a double-blind, randomized fashion. Appetite perceptions, antropyloroduodenal PWs, and plasma CCK and GLP-1 concentrations were measured during a 90-min intraduodenal infusion of 1) C12, 2) C10, or 3) control (rate: 2 ml/min, 0.375 kcal/min for C12/C10). Energy intake at a buffet meal, immediately after completion of the infusion, was also quantified. C12, but not C10, suppressed appetite perceptions ( P < 0.001) and energy intake (control: 4,604 ± 464 kJ, C10: 4,109 ± 588 kJ, and C12: 1,747 ± 632 kJ; P < 0.001, C12 vs. control/C10). C12, but not C10, also induced nausea ( P < 0.001). C12 stimulated basal pyloric pressures and isolated pyloric PWs and suppressed antral and duodenal PWs compared with control ( P < 0.05 for all). C10 transiently stimulated isolated pyloric PWs ( P = 0.001) and had no effect on antral PWs but markedly stimulated duodenal PWs ( P = 0.004). C12 and C10 increased plasma CCK ( P < 0.001), but the effect of C12 was substantially greater ( P = 0.001); C12 stimulated GLP-1 ( P < 0.05), whereas C10 did not. In conclusion, there are major differences in the effects of intraduodenal C12 and C10, administered at 0.375 kcal/min, on appetite, energy intake, antropyloroduodenal PWs, and gut hormone release in humans.

This study examined the effects of the lipase inhibitor, orlistat, on gastric emptying of, and the glycemic and incretin hormone responses to, a drink containing oil and glucose components in patients with type 2 diabetes. Seven patients (aged 58 5 yr), managed by diet alone, consumed 60 ml olive oil (labeled with 20 MBq 99m Tc-V-thiocyanate) and 300 ml water containing 75 g glucose (labeled with 6 MBq 67 Ga-EDTA), on two occasions, with and without 120 mg orlistat, positioned in the left lateral decubitus position with their back against a camera. Venous blood samples, for measurement of blood glucose and plasma insulin, glucagon-like peptide-1 and glucosedependent insulintropic polypeptide were obtained immediately before, and after, the drink. Gastric emptying of both oil (P < 0.001) and glucose (P < 0.0005) was faster after orlistat compared with control. Postprandial blood glucose (P < 0.001) and plasma insulin (P < 0.05) were substantially greater after orlistat compared with control. In contrast, plasma glucagonlike peptide-1 (P < 0.005) and glucose-dependent insulintropic polypeptide (P < 0.05) were less after orlistat. In conclusion, inhibition of fat digestion, by orlistat, may exacerbate postprandial glycemia, as a result of more rapid gastric emptying and a diminished incretin response. (J Clin Endocrinol Metab 88: 3829 –3834, 2003)

A 13-year-old boy presented to an outside hospital with complaints of intermittent left hip pain after playing football. The patient was thought to have a muscle strain. He was prescribed nonsteroidal antiinflammatory drugs for symptomatic relief, with instructions to temporarily abstain from vigorous sports activities. However, the hip pain persisted. He presented 3 months later to the current authors’ institution with the same complaints. He denied any history of trauma, fever or chills, weight loss, or other symptoms. His medical history was unremarkable. He was not taking any medications at that time. Orthopaedic • Radiology • Pathology Conference CME ARTICLE

The ability of nutrients in the intestinal lumen to exert feedback control over the proximal gastrointestinal tract function is well recognized, yet the control mechanisms are poorly defined. There is evidence that extrinsic sensory pathways from the intestine are required to initiate this regulatory process. Furthermore, CCK appears to be involved in the gastric response to several intestinal stimuli, such as fat, carbohydrate and protein. Our hypothesis is that nutrients release CCK from the intestine, which then stimulates intestinal mucosal afferents to signal reflex changes in gastric motor function and thus inhibit gastric emptying.

Magnetic resonance imaging (MRI) offers promise as a noninvasive method to determine the potential of an osteochondritis dissecans (OCD) lesion to heal without surgical intervention. The purpose of this study was to compare the value of MRI, plain radiographs, and clinical findings in predicting the success of nonoperative treatment of juvenile OCD lesions. Twenty-seven lesions in 24 patients (mean age 12.2 y) with OCD of the distal femur diagnosed based on MRI were identified. A radiologist or orthopaedist, blinded to the clinical status of the patients, correlated the MRIs with patient outcome. MRIs were assessed for lesion size, location, and four criteria evaluating signal intensity changes and articular surface defects to determine lesion stability. Older, more skeletally mature patients with at least one sign of instability on MRI were most likely to have nonoperative treatment fail. Nonoperative treatment failed most often in patients with large lesions in weightbearing areas, as seen on lateral radiographs. However, location based on anteroposterior radiographs was not statistically significant for predicting treatment outcome. Although no single factor was uniformly predictive of successful nonoperative treatment, younger, skeletally immature patients with no MRI criteria of instability were most amenable to nonoperative treatment.

Intestinal perfusion with carbohydrates inhibits gastric emptying via vagal and spinal capsaicin-sensitive afferent pathways. The aim of the present study was to determine the role of 1) 5-hydroxytryptamine (5-HT)3receptors (5-HT3R) in mediating glucose-induced inhibition of gastric emptying and 2) 5-HT3R expression in vagal and spinal afferents in innervating the duodenum. In awake rats fitted with gastric and duodenal cannulas, perfusion of the duodenum with glucose (50 and 100 mg) inhibited gastric emptying. Intestinal perfusion of mannitol inhibited gastric emptying only at the highest concentration (990 mosm/kgH2O). Pretreatment with the 5-HT3R antagonist tropisetron abolished both glucose- and mannitol-induced inhibition of gastric emptying. Retrograde labeling of visceral afferents by injection of dextran-conjugated Texas Red into the duodenal wall was used to identify extrinsic primary afferents. Immunoreactivity for 5-HT3R, visualized with an antibody directed to the COOH terminus of the rat 5-HT3R, was found in >80% of duodenal vagal and spinal afferents. These results show that duodenal extrinsic afferents express 5-HT3R and that the receptor mediates specific glucose-induced inhibition of gastric emptying. These findings support the hypothesis that enterochromaffin cells in the intestinal mucosa release 5-HT in response to glucose, which activates 5-HT3R on afferent nerve terminals to evoke reflex changes in gastric motility. The primary glucose sensors of the intestine may be mucosal enterochromaffin cells.

OBJECTIVE Worldwide attention over iron deficiency anemia (IDA) in pregnancy has shifted recently from providing supplements during pregnancy to attempting to ensure that women, especially adolescents, have adequate iron stores prior to conception. We sought to determine whether adolescent and/or adult women still need supplements during pregnancy to avoid IDA, even if iron stores are adequate, and whether the IDA translates into maternal and/or infant morbidity and mortality. DESIGN Randomized, double-blind clinical trial with placebo control. SETTING Multicenter clinic setting in central Wisconsin. PARTICIPANTS Adolescent women 18 years or less in their first pregnancy, and adult women 19 years or older, who were found to be healthy and iron sufficient at their first prenatal visit. METHODS Participants were randomized to receive iron supplementation (60 mg/day elemental iron) or placebo. Serum ferritin of 12 ng/mL or less with simultaneous hemoglobin of 11 g/dL or less defined IDA. When IDA occurred at the second trimester, a therapeutic supplement of 180 mg of elemental iron per day was initiated. RESULTS Forty-seven percent of all placebo-supplemented and 16% of all iron-supplemented patients exhibited IDA (p

BACKGROUND—Patients with gastro-oesophageal reflux disease (GORD) frequently report that meals high in fat worsen heartburn. Nevertheless, studies to determine whether high fat meals promote gastro-oesophageal reflux have produced conflicting and equivocal conclusions. PATIENTS AND METHODS—To determine, alternatively, whether fat in the small intestinal lumen intensifies the perception of heartburn, we studied 11 patients with typical heartburn from GORD. After being placed on omeprazole to suppress endogenous acid, these fasting subjects underwent oesophageal perfusions with graded doses of HCl at pH values of 1.0, 1.5, 2.0, and 2.5. Oesophageal perfusions were conducted while the duodenum was perfused with saline (control) and again with fat at 8 g/h. RESULTS—Time to onset, intensity, and severity of heartburn varied with dose of oesophageal acid (p

To determine what practices are being utilized in the management of intussusception, a survey was sent to chairpersons of 64 Pediatric Radiology departments in the United States and Canada. There was a 92% response rate. Barium is used in 97% of departments and is the most commonly used contrast-agent in 64%. Water-soluble contrast is used in 83% of departments and air in 50%. In high-risk patients, water soluble contrast is used in 71% of departments, air in 28% and barium in 24%. Glucagon, pre-exam antibiotics, and pre-exam sedation are not used regularly in a majority of departments. The radiologic management of intussusception is more varied than only a few years ago. Use of water-soluble contrast and air have increased, while barium use is less routine.

The objective of this paper is to evaluate the efficacy of various magnetic resonance imaging (MRI) sequences and the general usefulness of prenatal MRI in determining the position of the fetal liver and visualizing lung tissue in fetuses who have congenital diaphragmatic hernia (CDH). This was a retrospective review of prenatal MRI of fetuses with a confirmed diagnosis by surgery or autopsy of CDH. MRI was performed in a 1.5-Tesla magnet using fast gradient echo, half-Fourier single-shot turbo spin-echo (HASTE) and echo planar images. The presence of a chest mass, position of the stomach and liver and visualization of the lungs by MRI was noted in all fetuses. This was compared to ultrasound studies performed the same day and correlated with postnatal or autopsy studies. The fetuses were 18-36 weeks gestational age (mean 24.5 weeks). MRI diagnosed left CDH (33), right CDH (4), and bilateral CDH (1) and agreed with the postnatal diagnosis in all patients. Ultrasound (US) diagnosed left CDH (33), right CDH (2), and congenital cystic adenomatoid malformation (3). MRI changed the diagnosis in four patients. The fetal liver was easily demonstrated with MRI in all fetuses and was herniated into the chest in 25 of the 38. US diagnosed liver up in 21. Correlation with postnatal studies found MRI correctly diagnosed liver position in 37 out of 38 cases. US correctly diagnosed liver position in 32 out of 38. Both lungs could be visualized in all fetuses with MRI. MRI accurately and easily diagnoses CDH and can differentiate it from other chest masses. MRI was superior to US in demonstrating the position of the fetal liver above or below the diaphragm. MRI reliably visualized fetal lung tissue. These findings are important for counseling parents, selecting fetal surgical candidates, and estimating prognosis.

The differential between aneurysmal bone cysts and unicameral bone cysts usually is clear clinically and radiographically. Occasionally there are cases in which the diagnosis is not clear. Because natural history and treatment are different, the ability to distinguish between these two entities before surgery is important. The authors reviewed, in a blinded fashion, the preoperative magnetic resonance images to investigate criteria that could be used to differentiate between the two lesions. All patients had operative or pathologic confirmation of an aneurysmal bone cyst or unicameral bone cyst. The authors analyzed the preoperative magnetic resonance images of 14 patients with diagnostically difficult bone cysts (eight children with unicameral bone cysts and six children with aneurysmal bone cysts) and correlated these findings with diagnosis after biopsy or cyst aspiration and contrast injection. The presence of a double density fluid level within the lesion strongly indicated that the lesion was an aneurysmal bone cyst, rather than a unicameral bone cyst. Other criteria that suggested the lesion was an aneurysmal bone cyst were the presence of septations within the lesion and signal characteristics of low intensity on T1 images and high intensity on T2 images. The authors identified a way of helping to differentiate between aneurysmal bone cysts and unicameral bone cysts on magnetic resonance images. Double density fluid level, septation, and low signal on T1 images and high signal on T2 images strongly suggest the bone cyst in question is an aneurysmal bone cyst, rather than a unicameral bone cyst. This may be helpful before surgery for the child who has a cystic lesion for which radiographic features do not allow a clear differentiation of unicameral bone cyst from aneurysmal bone cyst.

Background. During the course of our routine renal ultrasound examinations, we noticed that some children who developed dilatation of a renal pelvis following voiding had reflux found on voiding cystourethrography (VCUG). Purpose. To determine if increase in renal pelvic size on post-void ultrasound is an accurate predictor of vesicoureteral reflux. Materials and methods. Fifty-seven children (113 kidneys) underwent renal ultrasound and VCUG on the same day. Anteroposterior dimensions of the renal pelves were prospectively measured on ultrasound prior to and following patient voiding and correlated with the results of the VCUG. Results. The diameter of the renal pelvis increased in 12 and decreased in 38 kidneys on post-void ultrasound. Vesicoureteral reflux occurred in 19 kidneys and among these kidneys, renal pelvic diameter increased in 2, decreased in 7, and was unchanged in 10 following voiding. There was no significant correlation between post-void change in renal pelvic diameter and the presence of vesicoureteral reflux. Conclusion. Increase in renal pelvic size on post-void ultrasound is not a reliable indicator of vesicoureteral reflux.

This work demonstrates encouraging results for increasing the automation of a practical and precise magnetic resonance brain image segmentation method. The intensity threshold for segmenting the brain exterior is determined automatically by locating the choroid plexus. This is done by finding peaks in a series of histograms taken over regions specified using anatomical knowledge. Intensity inhomogeneities are accounted for by adjusting the global intensity to match the white matter peak intensity in local regions. Automated results are incorporated into the established manually guided segmentation method by providing a trained expert with the automated threshold. The results from 20 different brain scans (over 1000 images) obtained under different conditions are presented to validate the method which was able to determine the appropriate threshold in approximately 80% of the data.

Ehlers-Danlos syndrome (EDS) type IV is a heritable disorder resulting from mutations in the COL3A1 gene that cause deficient production of type III collagen. Clinical manifestations of EDS type IV include hypermobility of small joints, excessive bruisability, thin translucent skin, poor wound healing, bowel rupture, and vascular rupture that is often fatal. A 14-year-old male without a family history of EDS died following multiple bowel and abdominal blood vessel ruptures. Even in areas apart from rupture sites, the bowel wall was thin because of diminished submucosa and muscularis propria. Similarly, the walls of blood vessels in bowel submucosa and elsewhere in the abdomen varied in thickness, and contained frayed and fragmented elastic tissue fibers. Fibroblasts cultured from the patient's skin secreted reduced quantities of type III collagen that was explained by a point mutation in one copy of the COL3A1 gene. EDS type IV should be strongly suspected in any patient with otherwise unexplainable bowel and/or vessel rupture.

Chemosensors throughout small bowel and colon inhibit food intakes when contacted by monomeric nutrients. We postulated that calorie-dependent inhibition of food intakes depended on additions of feedbacks from sensors in proximal and distal bowel contacted after high intakes of nutrients. Therefore, we determined how feedback from sensors in proximal gut interacted with feedback from simultaneously contacted sensors in distal bowel and whether suppression of nutrient intakes by intestinally perfused nutrients depended on length of gut contacted. Suppression of food intakes by maltose simply added to that from dodecanoate when both were present together either in proximal or distal small bowel. When dodecanoate was infused into proximal gut while maltose was infused distally, suppression of intake was threefold higher and was thus potentiated. Limiting contact of slowly absorbed lactose or oleate to 35 cm of jejunum nearly abolished the satiating potencies each exhibited during access to whole gut. The observations were consistent with our hypothesis.

This magnetic resonance imaging (MRI)-based morphometric analysis of cortical topography in the human brain is based upon the segmentation and parcellation of volumetric T1-weighted MRI data for a set of 20 young adult brains including 10 males and 10 females. For the most part, each parcellation unit (PU) of the neocortex corresponds to a single or a portion of a single gyrus. The volumes of each PU were computed for each brain. Subsets of PUs were also grouped so as to represent the neocortex for the frontal, temporal, parietal and occipital lobes. The coefficient of variation of the mean volume of total neocortex and that of the neocortex assigned to individual lobes cluster around 10%, whereas that of neocortex assigned to the individual gyri (PU) is more than twice that value. Approximately 80% of the total variance in gyral volume arises from determinants interactive for individual and specific gyri, while only approximately 10% of the total variance appears to be a reflection of uniform scaling to total neocortical volume. Sexual dimorphism contributes a pervasive though relatively small component of this variance. These results have implications for the study of structure-function correlation, and the proper statistical methods of handling volumetric data in morphometric studies. In addition, the nature of the covariance structure of the data will lead to future hypotheses regarding the relationships between the various potential genetic and epigenetic gyral influencing factors.

Lipid in the intestine initiates feedback inhibition of proximal gastrointestinal function and food intake. In rats and humans, inhibition of gastric emptying is mediated, at least in part, by cholecystokinin (CCK)-A receptors, and in rats there is evidence for involvement of an intestinal vagal afferent pathway. The mechanism by which luminal lipid acts to release CCK or activate vagal afferent nerve terminals is unclear. The role of chylomicron formation in this sensory transduction pathway has been investigated using the hydrophobic surfactant Pluronic L-81 that inhibits chylomicron formation. Gastric emptying of liquids was measured in awake rats fitted with a Thomas gastric fistula and a duodenal cannula. Intestinal perfusion of lipid induced a dose-dependent inhibition of gastric emptying (6, 12, and 39% inhibition for 25, 50, and 100 mg lipid, respectively). Perfusion of lipid with Pluronic L-81 (2.8% wt/vol) reversed the lipid-induced inhibition of gastric emptying. Pluronic L-63, a chemically similar surfactant that has no effect on chylomicron formation, had no effect on lipid-induced inhibition of gastric emptying. Perfusion of the intestine with lipid (100 mg) increased plasma levels of CCK from 1.9 ± 0.8 to 6.5 ± 1 pM. This increase was blocked by Pluronic L-81 but unaffected by L-63. These results provide evidence that chylomicron formation is important in the signaling of lipid in the intestinal lumen to CCK endocrine cells and to producing feedback inhibition of gastric emptying.

Summary A wide spectrum of malignant and benign diseases can present as tumors involving the chest in children. The imaging evaluation of these children is initially directed by clinical presentation and usually begins with a chest radiograph. Further imaging with CT, MRI, or rarely ultrasonography may be performed to better detect, localize, or characterize the lesion(s). The differential diagnosis of these tumors is guided not only by tumor location and characterization, but also by patient age and clinical presentation. Familiarity with the clinical and radiographic aspects of these diseases will help the radiologist to continue to play a crucial role in the diagnosis and management of these children.

Objective. In order to achieve more “timely” interpretation of radiologic examinations, a 3 to 11 p. m. attending radiologist slot was incorporated into the daily schedule utilizing existing staff. Our purpose was to assess the effectiveness of this practice by measuring report generation times. Material and methods. Using a radiology information system (DecRAD), the time between completion of the technical examination and dictation of the official report for general (plain film) studies was determined for a 2-month period and compared to similar periods 1 and 2 years prior to instituting extended hours. Emergency and portable (ICU) exams were similarly analyzed. Results. The number of examinations reported within 2 h of technical completion increased by 8.5 % (mean); reporting within 4 h increased by 20 %; reporting within 6 and 12 h of completion each increased by 24 %. Over 80 % of cases were dictated within 12 h after the change in practice occurred; whereas, it took up to 24 h in preceding years. Analysis of emergency and portable ICU exams showed similar trends, and the number of next day “call-backs” to the emergency department was significantly reduced. Conclusion. By extending attending coverage, more plain film examinations, especially emergency cases and ICU portables, were read and reported within a shorter time providing prompt communication with clinicians and more opportunity to influence management decisions.

This work demonstrates encouraging initial results for increasing the automation of a practical and precise MR brain image segmentation method. The intensity threshold for segmenting the brain exterior is automatically determined by locating the choroid plexus. This is done by finding peaks in a series of histograms taken over regions specified using anatomical knowledge. Intensity inhomogeneities are accounted for by adjusting the global intensity to match the white matter peak intensity in local regions. The results from 20 different brain scans (over 1000 images) obtained under different conditions are presented to validate the method which was able to determine the appropriate threshold in approximately 80% of the data.

Magnetic resonance imaging was used to visualize the ossified and unossified portions of the bones and soft tissues of the feet in order to evaluate the tarsometatarsal anatomy in sixteen children, three months to six years old (mean, fifteen months old), who were seen in the orthopaedic clinic with a suspected diagnosis of skewfoot. Twenty-seven feet were clinically abnormal and five were normal. Of the abnormal feet, twenty-six had a radiographic diagnosis of skewfoot and one, of simple metatarsus adductus. Of the skewfeet, seven had a talocalcaneal angle of 45 degrees or more as measured on the lateral radiograph and six had a talocalcaneal angle of 45 degrees or more as measured on the anterior radiograph. Valgus deformity of the hindfoot was not apparent on clinical examination in any of the children. The talocalcaneal angles measured on the magnetic resonance images corresponded poorly with those measured on the radiographs, possibly because it is not possible to simulate weight-bearing during magnetic resonance imaging or because the effect of partial volume averaging on thin sections. However, magnetic resonance imaging demonstrated the shapes of the bones and the positions of the unossified portions of the bones. Magnetic resonance imaging showed lateral subluxation of the navicular in twenty-four skewfeet, plantar subluxation in ten, and medial subluxation of the first metatarsal on the medial cuneiform in twenty-five. The alignment of the lateral margin of the calcaneus and cuboid on the magnetic resonance images was normal in all patients. Magnetic resonance imaging has the unique ability to show the cartilaginous and ossified portions of the developing bones of the foot.

Between May 1972 and December 1991, 58 children were seen in the authors' institution for treatment of Langerhans' cell histiocytosis. Of these, 15 children (7 males, 8 females) had biopsy-proven Langerhans' cell histiocytosis with vertebral involvement. The average age at presentation was 6.4 years (range, 0.2-13.3 years). At presentation, 8 patients had involvement of a single vertebra and 4 had involvement of multiple vertebrae. Nine patients had extraspinal skeletal involvement. Two patients had visceral involvement. Currently, 13 patients have had >2 years followup (average, 8.9 years ; range, 2-21 years). None of these patients had clinical evidence of disease at the latest encounter. This group of patients with Langerhans' cell histiocytosis with vertebral involvement has fared well. Most patients have had involvement of multiple vertebrae and many have had extraspinal bony involvement as well. There was a great deal of variability in the extent of collapse and reconstitution of vertebral height, and the amount of reconstitution did not correlate with patient age.

Radiologic images and medical records of 42 children with Langerhans cell histiocytosis (LCH) (histiocytosis X) were reviewed to evaluate the presentation of the disease and the evolution of the radiologic findings. There were 26 male and 16 female patients aged 3 months to 18 years. Twenty-two patients presented with localized disease; 20 presented with multifocal disease. Four patients developed diabetes insipidus. Two patients had organ dysfunction. The radiologic findings were largely due to destructive bone lesions; 83% of the patients had at least one affected bone. Isolated soft-tissue masses, interstitial lung disease, and central nervous system abnormalities were also seen. Of patients in whom results of appropriate follow-up were available, 91% showed improvement in their lesions, 43% developed new lesions, and 92% had good clinical outcomes. LCH is usually a self-limited disease with a varied clinical and radiologic presentation. The prognosis is generally poor in children with organ dysfunction. In the absence of organ dysfunction, children with either localized or multifocal LCH have an excellent prognosis.

The aims of this study were to evaluate the effects of posture on gastric emptying, intragastric distribution, and satiation after a meal containing oil and aqueous phases in patients with exocrine pancreatic insufficiency. Five patients with cystic fibrosis (CF) consumed 60 ml 99mTc-labeled (V)-thiocyanate olive oil and 290 ml 113mIn-labeled diethylenetriaminepentaacetic acid soup while sitting and while lying in the left lateral decubitus position. Hunger and fullness before and after the meal were recorded. Results were compared with those obtained in 11 normal volunteers. In both postures emptying of oil was faster (P < 0.01) in CF patients. Emptying of the aqueous phase was faster (P < 0.01) in CF patients in the decubitus position. In normal subjects there was no overall difference in emptying of oil between the two postures, whereas emptying of the aqueous phase was delayed (P < 0.01) in the decubitus position. In CF patients emptying of oil was faster (P < 0.01) in the decubitus position, and emptying of the aqueous phase was only slightly faster (P < 0.05) in the sitting position. For both postures there was greater retention (P < 0.05) of oil in the proximal stomach in normal subjects than CF patients. Hunger decreased (P < 0.05) after the meal in the control subjects, but there was no change in CF patients. These results indicate that in CF patients with pancreatic exocrine insufficiency 1) gastric emptying of nonhomogenized fat is faster than normal, 2) gravity affects gastric emptying of oil, and 3) effects of a fatty meal on hunger are reduced.

Focal fibrocartilaginous dysplasia (FFCD) is an uncommon, benign condition associated with unilateral tibia vara in young children. The clinical, pathologic, plain film, and magnetic resonance imaging (MRI) findings of FFCD were reviewed in two children. MRI findings were virtually identical in both patients and correlated well with the plain film and pathologic findings. We believe that FFCD has a typical MRI appearance. However, FFCD also has characteristic plain film findings, and when these are present, MRI is indicated for only an atypical clinical presentation.

We studied gallbladder emptying with gamma scintigraphy in nine dogs prepared with chronic pancreatic fistulas, so that pancreatic enzymes could be either completely excluded from the duodenum or supplied in normal amounts. During duodenal perfusion of the fasted dogs with fat emulsions, gallbladder emptying was significantly less rapid when the emulsion contained inactive vs active enzymes, confirming the potency of lipolytic products in the intestine as stimuli of gallbladder emptying. However, after feeding either a 115-g or a 460-g meal, each 18% fat, the gallbladders emptied identically whether or not pancreatic enzymes were excluded from the duodenum. We concluded that while products of pancreatic lipolysis in the small intestine are potent stimuli of gallbladder contraction, preduodenal mechanisms can compensate completely for the absence of pancreatic hydrolysis in stimulating gallbladder emptying after a meal.

9537 Background: Patients (pts) with Ewing sarcoma (EWS) require local control, either with surgery alone (S), radiation alone (R), or a combination of surgery + radiation (S+R). Optimal choice of local control for disease control remains unclear. Our primary aim was to determine the mode of local control associated with the highest event-free survival (EFS). Methods: Pts with localized EWS of bone treated on INT0091, INT0154, or AEWS0031 phase III trials were included if they had complete local control data, did not have cranial tumors, received local control starting 2-6 months after enrollment, and were randomized to receive standard dose 5-drug chemotherapy every 3 weeks. We used propensity scores to control for differences in age, tumor site, and year of diagnosis between local control groups. We constructed Cox models controlling for local control propensity scores to assess the impact of local control type on EFS and overall survival (OS) from the start of local control. Results: 465 pts were included. Pts selected for S were treated more recently (p < 0.001), more likely to have appendicular tumors (p < 0.001), and younger (p = 0.02). Pts treated with R, compared to S, had higher unadjusted risk of any event (HR 1.70; 95% CI 1.18 - 2.44; p = 0.004) or death (HR 1.84; 95% CI 1.18 – 2.85; p = 0.006). Pts treated with S+R, compared to S, had higher unadjusted risk of death (HR 1.75; 95% CI 1.10 – 2.76; p = 0.02). After adjusting for propensity scores, there was a trend of higher risk of any event for pts treated with R (HR 1.42; 95% CI 0.94 – 2.14; p = 0.10) compared to S, though this was not statistically significant. No other differences in adjusted risk of event or death between local control groups were statistically significant. We confirmed these results with standard Cox models using age, tumor site, and year of diagnosis as covariates. Conclusions: In this large group of uniformly treated pts, investigator choice of local control approach was not significantly related to EFS. These data support current practice of surgical resection when feasible, while validating radiotherapy as a reasonable alternative in selected pts.

In animals, ileal sensors of nutrients signal satiety more potently than similar sensors in jejunum. We postulated that inadequate food intake and weight loss in human pancreatic insufficiency might arise by the displacement of digestion to ileum, where excessive release of digestive products would enhance satiety. To test this idea, we studied dogs prepared with pancreatic fistulas, which allowed reversible switching of pancreatic juice from entry at duodenum to entry at mid-small intestine. Dogs were studied in a crossover design over successive eight-day periods. Food consumption and body weight were measured while the dogs had continuous access to food. Diversion of pancreatic juice to mid-intestine significantly (P