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Biomedical subjects

Reza Shaker

Publications and source records attributed to Reza Shaker.

At least 37 records · Page 2Linked to original sources
PubMed2005

Cingulate cortex: a closer look at its gut-related functional topography.

Earlier studies have documented activation of the cingulate cortex during gut related sensory-motor function. However, topography of the cingulate cortex in relationship to various levels of visceromotor sensory stimuli and gender is not completely elucidated. The aim was to characterize and compare the activation topography of the cingulate cortex in response to 1) subliminal, 2) perceived rectal distensions, and 3) external anal sphincter contraction (EASC) in males and females. We studied 18 healthy volunteers (ages 18-35 yr; 10 women, 8 men) using functional MRI blood-oxygenation-level-dependent technique. We obtained 11 axial slices (voxel vol. 2.5-6.0 x 2.5 x 2.5 mm(3)) through the cingulate cortex during barostat-controlled subliminal, liminal, and supraliminal nonpainful rectal distensions as well as EASC. Overall, for viscerosensation, the anterior cingulate cortex exhibited significantly more numbers of activated cortical voxels for all levels of stimulations compared with the posterior cingulate cortex (P < 0.05). In contrast, during EASC, activity in the posterior cingulate was larger than in the anterior cingulate cortex (P < 0.05). Cingulate activation was similar during EASC in males and females (P = 0.58), whereas there was a gender difference in anterior cingulate activation during liminal and supraliminal stimulations (P < 0.05). In females, viscerosensory cortical activity response was stimulus-intensity dependent. Intestinal viscerosensation and EASC induce different patterns of cingulate cortical activation. There may be gender differences in cingulate cortical activation during viscerosensation. In contrast to male subjects, females exhibit increased activity in response to liminal nonpainful stimulation compared with subliminal stimulation suggesting differences in cognition-related recruitment.

Adolescent↗
PubMed2005

Optimal stimulus intensity and reliability of air stimulation technique for elicitation of laryngo-upper esophageal sphincter contractile reflex.

To determine the optimal air stimulus intensity and duration for elicitation of the laryngo-upper esophageal sphincter (UES) contractile reflex, we studied 37 healthy volunteers 20 to 81 years of age. A sleeve device monitored the UES pressure. For laryngeal stimulation, we used an air stimulator unit (Pentax AP-4000) that incorporated a nasolaryngeal endoscope. The arytenoids and interarytenoid areas were stimulated at least three times by three different stimuli: 6-mm Hg air pulse with 50-ms duration, 10-mm Hg air pulse with 50-ms duration, and 6-mm Hg air pulse with 2-second duration. Of 1,165 air stimulations, 1,041 resulted in mucosal deflections. Of these, 451 resulted in an abrupt increase in UES pressure. The response/deflection ratio for 6-mm Hg stimulation with 2-second duration was significantly higher than those for air pulses with 50-ms duration (p < .001). We conclude that although the laryngo-UES contractile reflex can be elicited by an air pulse with 50-ms duration, this ultrashort stimulation is not reliable. Using longer-duration pulses (at least 2 seconds) improves the reliability of elicitation of the laryngo-UES contractile reflex.

Adult↗
PubMed2004

Acute nociceptive somatic stimulus sensitizes neurones in the spinal cord to colonic distension in the rat.

The common co-existence of fibromyalgia and chronic abdominal pain could be due to sensitization of spinal neurones (SNs), as a result of viscero-somatic convergence. The objective of this study is to explore the influence of acute nociceptive somatic stimulation in the form of acid injections, into the ipsilateral somatic receptive field of neurones responsive to colorectal distension (CRD), and the potential role of ionotropic glutamate receptors on sensitization. Action potentials of CRD-sensitive SNs were recorded extracellularly from the lumbar (L(2)-L(5)) spinal cord. Stimulus-response functions (SRFs) to graded CRD (10-80 mmHg, 30 s) were constructed before and 30 min after ipsilateral injection of low pH (4.0, 100 microl) saline into the somatic receptive fields. In some experiments, cervical (C(1)-C(2)) spinalization was performed to eliminate supraspinal influence. The selective NMDA receptor antagonist CGS 19755 and AMPA receptor antagonist NBQX were injected (25 micromol kg(-1), i.v.) to examine their influence on sensitization. Three types of neurones were characterized as short-latency abrupt (SLA, n = 24), short latency sustained (SLS, n = 12), and long-latency (LL, n = 6) to CRD. Ipsilateral injection of low pH (4.0) in the somatic receptive field, but not the contralateral gastrocnemius (GN) or front leg muscles, sensitized responses of these neurones to CRD. Spinalization had no influence on the development of low pH-induced sensitization. Both CGS 19755 and NBQX significantly attenuated the sensitized response to CRD in intact and spinalized animals. Acute nociceptive somatic stimulus sensitizes CRD-sensitive SNs receiving viscero-somatic convergence. The sensitization occurs at the spinal level and is independent of supraspinal influence. Ionotropic glutamate receptors in the spinal cord are involved in sensitization.

Acids↗
PubMed2004

Differential activation of medullary vagal nuclei during different phases of swallowing in the cat.

The aim of this study was to identify the medullary vagal nuclei involved in the different phases of swallowing activated physiologically in a species with an esophagus similar to human. In decerebrate cats, the pharyngeal (0.5-1.0 ml water in pharynx (N=6)) or esophageal (1-3 ml air in esophagus (N=5)) phases of swallowing were stimulated separately once per minute for 3 h, and we compared the resulting c-fos immunoreactivity within neuronal cell nuclei of the dorsal motor nucleus (DMN), nucleus tractus solitarius (NTS) and nucleus ambiguus (NA) with a sham control group (N=5). We found that the pharyngeal phase was associated with an elevated number of c-fos positive neurons in the intermediate (NTSim), interstitial (NTSis), ventromedial (NTSvm) subnuclei of the NTS, caudal DMN, and dorsal NA; and the esophageal phase was associated with an elevated number of c-fos positive neurons in the central (NTSce), ventral, dorsolateral, ventrolateral subnuclei of the NTS, rostral DMN, and ventral NA. We concluded that the pharyngeal and esophageal phases of swallowing are associated with different sets of NTS subnuculei; and the DMN and NA may contain functionally different populations of motor neurons situated rostrocaudally and dorsoventrally associated with the different phases of swallowing. The central pattern generator (CPG) for swallowing probably receives significant peripheral feedback, and the NTSvm may participate in the transition of the pharyngeal to the esophageal phase of swallowing.

Animals↗
PubMed2004

Nighttime GERD: clinical implications and therapeutic challenges.

Limited available data specifically addressing nocturnal gastroesophageal reflux indicate its association with more severe injuries such as esophagitis and stricture, adenocarcinoma of the esophagus, respiratory and ENT disorders as well as sleep disturbances, diminished quality of life and undesired changes in activities of daily living. In a recent survey, altogether 79% of respondents reported experiencing heartburn at night. Among those, 75% reported that symptoms affected their sleep, 63% believed that heartburn negatively affected their ability to sleep well, and 40% believed that nocturnal heartburn impaired their ability to function the following day. Of the 791 respondents with nighttime heartburn, 71% reported taking over-the-counter medicine for it, only 29% of these rated this approach extremely effective. Forty-one percent reported trying prescription medicines and 49% of these rated this approach extremely satisfactory. This recent understanding of the prevalence and impact of nighttime heartburn is an indicator of nocturnal acid reflux events and suggests that nighttime heartburn occurs in a large majority of adults with gastroesophageal reflux disease. The fact that expected result from implemented therapy for heartburn is not achieved by a sizable percentage of patients can have significant management implications.

Gastroesophageal Reflux↗
PubMed2004

Eosinophilic esophagitis in adults: an emerging problem with unique esophageal features.

BACKGROUND: Eosinophilic esophagitis is an inflammatory condition in which there is dense eosinophilic infiltration of the surface lining of the esophagus. Reports of eosinophilic esophagitis pertain almost exclusively to pediatric populations. However, eosinophilic esophagitis is emerging as a clinical affliction of adults. This report describes the clinical and endoscopic findings of eosinophilic esophagitis in the largest cohort of adult patients reported to date. METHODS: Twenty-nine patients (21 men, 8 women; mean age 35 years) with documented eosinophilic esophagitis (>/=15 eosinophils per high-power field in biopsy specimens) and a significant history of chronic dysphagia for solid food (24 patients) were evaluated clinically and endoscopically during a 3-year period (1999-2002). Fourteen patients (48%) had a history of asthma, environmental allergy, or atopy. In a subset of 15 patients, the diagnostic accuracy of endoscopy was compared with that of barium contrast esophagography. RESULTS: Twenty-seven patients (93%) had abnormal endoscopic findings; 25 (86%) had unique esophageal structural changes, associated with a preserved mucosal surface, that were highly atypical for acid reflux injury. Structural alterations seen in adult patients with eosinophilic esophagitis may occur in combination or as a primary characteristic, e.g., uniform small-caliber esophagus, single or multiple corrugations (rings), proximal esophageal stenosis, or 1 to 2 mm whitish vesicles scattered over the mucosal surface. Barium contrast radiography combined with swallow of a barium-coated marshmallow identified 10 (67%) of the primary features observed endoscopically in 15 patients. However, radiography failed to detect other features noted at endoscopy (e.g., only 3/6 patients with proximal stenosis, 5/9 patients with concentric rings and none of 4 patients with small caliber esophagus). Eight of the 29 patients (20%) had a history of chronic heartburn. Twelve patients had been treated with a proton pump inhibitor and only 3 reported some improvement in the severity of dysphagia. CONCLUSIONS: Relatively young age, a history of chronic dysphagia for solid food, and endoscopic detection of unique structural alterations atypical for GERD in an adult patient should prompt a suspicion of EE and subsequent biopsy confirmation. Acid reflux appears to have a secondary role in eosinophilic esophagitis. In an uncontrolled comparison, endoscopy was superior to barium contrast radiography for the diagnosis of eosinophilic esophagitis. The incidence of eosinophilic esophagitis in adults appears to be increasing.

Adult↗
PubMed2004

Altered visceral sensation in response to somatic pain in the rat.

BACKGROUND & AIMS: Patients with fibromyalgia commonly have symptoms of abdominal pain, suggesting that altered somatic afferent activity may influence visceral sensations. It is hypothesized that a noxious somatic stimulus increases input to the projection neurons in the dorsal horn, resulting in visceral hyperalgesia. METHODS: Two injections (100 microL, pH 4.0) were given unilaterally in the gastrocnemius muscle 2 days apart in male Sprague-Dawley rats. Paw withdrawal reflex (PWR) was measured to assess somatic pain. The control group received pH 7.2 saline injections. Similar injections (pH 4.0) were given in the front leg in a different group. Electromyography (EMG) from the external oblique muscle was recorded to graded colorectal distention at different time intervals. NMDA receptor antagonist (CGS-19755, 20 nmol) or AMPA/kainate receptor antagonist (NBQX, 20 nmol) was injected intrathecally before low-pH injections. RESULTS: A bilateral decrease in PWR threshold occurred 72 hours after the second low-pH injection. There was no decrease in the threshold in rats injected with pH 7.2 saline. A significant increase in EMG to colorectal distention (> or =30 mm Hg) occurred at 72 hours and 2 weeks in the pH 4.0 group. No change in EMG was observed following 2 unilateral low-pH injections in the front leg. Both the visceral hyperalgesia and the decrease in somatic pain thresholds were prevented by prior intrathecal CGS-19755 or NBQX injections. CONCLUSIONS: Noxious somatic afferent input from the hind limb facilitates visceral hyperalgesia, which is due to viscerosomatic convergence in the lower spinal cord. This can be blocked by ionotropic glutamate receptor antagonists.

Abdominal Pain↗
PubMed2004

Laryngo-upper esophageal sphincter contractile reflex in humans deteriorates with age.

BACKGROUND & AIMS: Recent studies have shown the existence of several reflex connections between the aerodigestive and upper gastrointestinal tracts. Our aim was to study the effect of laryngeal stimulation on upper esophageal sphincter (UES) pressure and to determine the reproducibility of this effect. METHODS: We studied 14 young and 10 elderly healthy nonsmoker volunteers and 7 patients with UES dysphagia using a concurrent manometric and video endoscopic technique. Three levels of laryngeal air stimulation were studied: 6 mm Hg/50 ms, 10 mm Hg/50 ms, and 6 mm Hg/2 s. Ten young subjects were studied twice. RESULTS: For 6-mm Hg/2-s and 6-mm Hg/50-ms duration stimuli, the frequency of UES response to air stimulation as evidenced by mucosal deflection (response/deflection ratio) in the elderly volunteers was significantly lower compared with that of young subjects (P < 0.05). The response/deflection ratio of the 6-mm Hg/2-s stimulus was significantly higher than those induced by stimuli of shorter duration (P < 0.01). Poststimulation UES pressure was significantly higher than prestimulation pressure (P < 0.05) in both groups. The magnitude of the increase in poststimulation UES pressure in the elderly volunteers was similar to that of the young subjects. Findings were similar in repeated studies. Four of 7 dysphagic patients exhibited an abnormal response. CONCLUSIONS: Afferent signals originating from the larynx reproducibly induce contraction of the UES: the laryngo-UES contractile reflex. This reflex is elicited most reliably by 6-mm Hg/2-s air stimulation. Frequency elicitation of this reflex decreases significantly with age while the magnitude of change in UES pressure remains unchanged, indicating a deleterious effect of aging on the afferent arm of this reflex. This reflex is altered in some dysphagic patients.

Adult↗
PubMed2004

Physical and pH properties of gastroesophagopharyngeal refluxate: a 24-hour simultaneous ambulatory impedance and pH monitoring study.

OBJECTIVES: Frequency occurrence of nonacidic and nonliquid reflux events in the pharynx has not been systematically studied. The aim of the present study was to characterize the physical (liquid, gas, and mixed gas/liquid) and pH properties of the gastroesophagopharyngeal refluxate. METHODS: We performed a total of 31 24-h simultaneous ambulatory pharyngoesophageal impedance and pH recordings in 11 GERD patients, 10 patients with reflux-attributed laryngitis, and 10 healthy controls. RESULTS: On average, the total number of reflux events (all kinds) in the pharynx was less than half of that in the proximal esophagus (18 +/- 4 vs 50 +/- 4, p < 0.01). Most of the pharyngeal reflux events were gas events and were observed in all three studied groups. Prevalence of these gas reflux events ranged between 0 and 74. The number of gas reflux events accompanied by a minor pH drop in laryngitis patients (1 (0-36)) was significantly higher than those in GERD and controls (0 (0-2) and 0 (0-1), respectively, p < 0.05). There was no significant difference in the number of nonacidic gas reflux events among the three groups (GERD: 10 (2-57), laryngitis: 11.5 (0-51), controls: 10.5 (0-27)). Impedance recording identified a total number of 566 events in the pharynx. Of these, a total of 563 events were compatible with gas reflux events, 101 events were accompanied by minor drops in intrapharyngeal pH, whereas 460 events were not accompanied by any pharyngeal pH change. CONCLUSIONS: Concurrent impedance and pH recordings detect significantly more events qualifying as reflux in the pharynx than pH recordings alone. A substantial majority of these events are gaseous refluxes both with and without minor pH drops. Gas reflux events with weak acidity appear to be more common among patients with reflux-attributed laryngeal lesions compared to GERD patients and controls.

Adult↗
PubMed2004

Effect of lower esophageal sphincter tone and crural diaphragm contraction on distensibility of the gastroesophageal junction in humans.

Previous studies of distensibility of the gastroesophageal junction (GEJ) in humans have not tried to distinguish between the effects of muscle action and passive elastic tissue properties of the GEJ. We studied 15 healthy subjects (ages 23-67 yr, 11 men/4 women) by using a catheter with a highly complaint bag positioned manometrically at the GEJ. The bag was distended with air at a rate of 20 ml/min while intrabag pressure was recorded. Distensions were performed during normal breathing, with breath held at maximum inspiration (MI) to activate the diaphragmatic crura, and with midesophageal balloon distension (BD) to relax the lower esophageal sphincter. In 10 subjects, distensions were performed after atropine injection (12 microg/kg iv). Pressure-volume curves and incremental distensibility values were calculated and compared among the different conditions. Both MI and BD significantly altered the slopes of the pressure-volume curves, whereas no effect was seen with atropine. Maximum distensibility was seen at the volume increment of 5-10 ml and was reduced with larger volumes. Distensibility measurements for the various test conditions tended to converge at the largest volume increment, suggesting that distensibility at this degree of distension was more related to the passive elastic properties of the GEJ. On the basis of these findings, we conclude that there can be significant active muscular contributions to recordings of distensibility at the GEJ, variations that must be controlled for during different study conditions.

Adult↗
PubMed2004

Absence of increasing cortical fMRI activity volume in response to increasing visceral stimulation in IBS patients.

Cerebral cortical activity associated with perceived visceral sensation represents registration of afferent transduction and cognitive processes related to perception. Abnormalities of gut sensory function can involve either or both of these processes. Cortical registration of subliminal viscerosensory signals represents cerebral cortical activity induced by stimulation of intestinal sensory neurocircuitry without the influence of perception-related cortical activity, whereas those associated with perception represent both neural circuitry and cognitive processes. Our aims were to determine and compare quantitatively cerebral cortical functional magnetic resonance imaging (fMRI) activity in response to subliminal, liminal, and nonpainful supraliminal rectal distension between a group of irritable bowel syndrome (IBS) patients and age/gender-matched controls. Eight female IBS patients and eight age-matched healthy female control subjects were studied using brain fMRI techniques. Three barostat-controlled distension levels were tested: 1) 10 mmHg below perception (subliminal), 2) at perception (liminal), and 3) 10 mmHg above perception (supraliminal). In control subjects, there was a direct relationship between stimulus intensity and cortical activity volumes, ie., the volume of fMRI cortical activity in response to subliminal (3,226 +/- 335 microl), liminal (5,751 +/- 396 microl), and supraliminal nonpainful stimulation (8,246 +/- 624 microl) were significantly different (P < 0.05). In contrast, in IBS patients this relationship was absent and fMRI activity volumes for subliminal (2,985 +/- 332 microl), liminal (2,457 +/- 342 microl), and supraliminal nonpainful stimulation (2,493 +/- 351 microl) were similar. Additional recruitment of cortical fMRI activity volume in response to increasing stimulation from subliminal to liminal and supraliminal domains is absent in IBS patients, suggesting a difference in the processing of perceived stimulation compared with controls.

Adult↗
PubMed2004

The promise and perils of exhaled breath condensates.

The exhaled breath condensate (EBC) approach provides a convenient and noninvasive approach for sampling the pulmonary epithelial lining fluid (ELF). Increased EBC concentrations of more than a dozen inflammatory markers and hydrogen ions have been reported in lung diseases associated with inflammation. However, the usefulness of EBC is compromised by uncertainties concerning the sources of the EBC droplets and by the extreme and variable dilution of ELF droplets with condensed water vapor ( approximately 20,000-fold). Reported increases in EBC concentrations may reflect proportionate increases in the total volume rather than the concentration of ELF droplets in the collected samples. Conclusions regarding ELF concentrations can only be made if this dilution is estimated with a dilutional indicator (e.g., conductivity of lyophilized EBC). In normal EBC samples, pH is effectively set by oral contamination with NH(3), and EBC pH cannot provide reliable information regarding ELF pH in normal subjects. Acidification of EBC observed in asthma and other conditions may reflect acidification of ELF, decreases in NH(3) added to the EBC, and/or the presence of gastric droplets in the EBC.

Breath Tests↗
PubMed2003

Characterization of the cerebral cortical representation of heartburn in GERD patients.

Although symptoms arising from the esophagus such as heartburn and pain can at times become challenging clinical problems, esophageal viscerosensation, especially with regard to chemical stimulation in humans, is incompletely understood. Our aims were 1) to characterize and ascertain the reproducibility of cerebral cortical registration of heartburn and 2) to elucidate the differences between these findings and those of esophageal subliminal acid stimulation in asymptomatic controls. We studied 11 gastroesophageal reflux disease (GERD) patients (9 males, 30-55 yr) and 15 healthy controls (8 males, 21-49 yr). Cerebral cortical functional magnetic resonance imaging (fMRI) activity was recorded twice in each subject, during two 5-min intervals of 0.1 N HCl, separated by 5 min of NaCl perfusion. Time from onset of acid perfusion to instant of fMRI signal increase and first report of heartburn averaged 1.60 +/- 0.80 and 1.85 +/- 0.60 min, respectively. Average maximum percent signal increase in the GERD patients (16.3 +/- 3.5%) was significantly greater than that of healthy controls (3.8 +/- 0.9%; P < 0.01). Temporal fMRI signal characteristics during heartburn were significantly different from those of subliminal acid stimulation in controls (P < 0.01). Activated cortical regions included sensory/motor, parieto-occipital, cingulate and prefrontal regions, and the insula. There was 92% concordance between the activated Brodmann areas in repeated studies of GERD patients. Cortical activity associated with perceived and unperceived esophageal acid exposure in GERD patients and healthy controls, respectively, involves multiple brain regions but occurs more rapidly and with greater intensity in GERD patients than the activity in response to subliminal acid exposure in healthy controls. The cortical pain-processing pathway seems to be involved in perception of esophageal acid exposure and could explain the variations encountered in clinical practice defining this sensation.

Adult↗