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2.
Am J Physiol Gastrointest Liver Physiol ; 294(3): G787-94, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18187518

ABSTRACT

The cingulate and insular cortices are parts of the limbic system that process and modulate gastrointestinal sensory signals. We hypothesized that sensitization of these two limbic area may operate in esophageal sensitization. Thus the objective of the study was to elucidate the neurocognitive processing in the cingulate and insular cortices to mechanical stimulation of the proximal esophagus following infusion of acid or phosphate buffer solution (PBS) into the esophagus. Twenty-six studies (14 to acid and 12 to PBS infusion) were performed in 20 healthy subjects (18-35 yr) using high-resolution (2.5 x 2.5 x 2.5 mm(3) voxel size) functional MRI (fMRI). Paradigm-driven, 2-min fMRI scans were performed during randomly timed 15-s intervals of proximal esophageal barostatically controlled distentions and rest, before and after 30-min of distal esophageal acid or PBS perfusion (0.1 N HCl or 0.1 M PBS at 1 ml/min). Following distal esophageal acid infusion, at subliminal and liminal levels of proximal esophageal distentions, the number of activated voxels in both cingulate and insular cortices showed a significant increase compared with before acid infusion (P < 0.05). No statistically significant change in cortical activity was noted following PBS infusion. We conclude that 1) acid stimulation of the esophagus results in sensitization of the cingulate and insular cortices to subliminal and liminal nonpainful mechanical stimulations, and 2) these findings can have ramifications with regard to the mechanisms of some esophageal symptoms attributed to reflux disease.


Subject(s)
Cerebral Cortex/physiology , Cognition/physiology , Esophagus/innervation , Esophagus/physiology , Gyrus Cinguli/physiology , Adolescent , Adult , Catheterization , Dilatation , Female , Gastroesophageal Reflux/physiopathology , Humans , Hydrochloric Acid/pharmacology , Hydrogen-Ion Concentration , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Nerve Net/physiology , Pain/physiopathology , Physical Stimulation , Stimulation, Chemical
3.
Curr Opin Gastroenterol ; 23(6): 625-30, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17906438

ABSTRACT

PURPOSE OF REVIEW: This review focuses on progress made in the field of gastric motility in the past year, emphasizing advances in understanding the motor physiology of the stomach in health and disease; noninvasive imaging technology and data on novel pharmacotherapeutics and other therapeutic interventions for gastroparesis. RECENT FINDINGS: The differential conduction pattern in the interstitial cell of Cajal is responsible for the generation of the full spatio-temporal pattern of gastric peristalsis. The mitochondrial powerhouse provides the driving potential for the gastric slow waves. Females are more dependent on the nitrenergic system for gastric relaxation, which is predominantly affected in diabetes. The noninvasive modalities to evaluate gastric function have undergone substantial evolution in the past year. On the therapeutic front, a new generation of medications has been tested and holds promise for the near future. Gastric electrical stimulation is a viable option for medically refractory gastroparesis. SUMMARY: Using dynamic imaging modalities, the pathophysiology of dyspepsia is becoming better understood and recognized as an end point of multifactorial dysfunction of the enteric neural circuitry. Mechanism-targeted drugs, stem cell transplantation and electrical stimulation options are becoming available.


Subject(s)
Dyspepsia/physiopathology , Gastrointestinal Motility/drug effects , Gastrointestinal Motility/physiology , Animals , Botulinum Toxins, Type A/pharmacology , Botulinum Toxins, Type A/therapeutic use , Diabetes Complications/drug therapy , Electric Stimulation Therapy , Gastric Emptying/drug effects , Gastric Emptying/physiology , Gastroparesis/diagnosis , Gastroparesis/drug therapy , Gastroparesis/therapy , Humans , Neuromuscular Agents/pharmacology , Neuromuscular Agents/therapeutic use
4.
Am J Physiol Gastrointest Liver Physiol ; 289(4): G722-30, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16160081

ABSTRACT

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.


Subject(s)
Cerebral Cortex/physiology , Digestive System/innervation , Adolescent , Adult , Cerebral Cortex/anatomy & histology , Data Interpretation, Statistical , Echo-Planar Imaging , Female , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Muscle Contraction/physiology , Neural Pathways/anatomy & histology , Neural Pathways/physiology , Rectum/innervation , Rectum/physiology , Sex Characteristics
6.
Int J Gastrointest Cancer ; 34(1): 49-54, 2003.
Article in English | MEDLINE | ID: mdl-15235135

ABSTRACT

BACKGROUND: Identifying subjects at an increased risk of colorectal cancer (CRC) is of considerable importance in designing effective screening strategies. Malignancies that cosegregate with CRC provide important markers for higher-risk patients. CRC and prostate cancer share many similarities with regard to etiological factors. However, the previous reports on associations between these common malignancies are contradictory and confounded by a lack of rigorous controls. AIM OF THE STUDY: The aim of this study was to further elucidate the relationship between CRC and prostate cancer. METHODS: We performed a retrospective case-control study of subjects receiving medical care at the Omaha Veteran's Administration Medical Center between 1992 and 2002. Cases (patients with CRC) were obtained through the pathology records, whereas controls (patients with a negative colonoscopy during the same time period) were found through assessment of the endoscopy database. All subjects had the pathology database queried for other malignancies. The medical record also was assessed for confounding factors such as prostate cancer screening, radiation therapy status, and so on. RESULTS: We identified 149 male patients with CRC cases and 186 controls (age-matched male patients with a negative colonoscopy). The 10-yr cumulative incidence of prostate cancer was 10.7% of the cases but only 3.8% of the controls (p = 0.016). There were no significant differences between cases and controls among 11 other primary malignancies evaluated. The association between CRC and prostate cancer was unrelated to characteristics such as location in the colon and differentiation. Furthermore, confounding factors including frequency of prostate cancer screening and radiation therapy status did not explain the cosegregation between CRC and prostate. CONCLUSION: This preliminary report suggests that there is an association between CRC and prostate cancer. If replicated in other populations, this may have important implications for cancer screening strategies.


Subject(s)
Colorectal Neoplasms/complications , Prostatic Neoplasms/epidemiology , Adult , Aged , Aged, 80 and over , Case-Control Studies , Colonoscopy , Databases, Factual , Humans , Incidence , Male , Mass Screening , Middle Aged , Prostatic Neoplasms/etiology , Retrospective Studies , Risk Factors
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