Effects of 5-HT(3) antagonism on postprandial gastric volume and symptoms in humans.

BACKGROUND: Alosetron reduces symptoms of dyspepsia, but the physiological basis for the symptomatic benefit is unclear. AIM: To assess 5-HT3 antagonism on postprandial gastric volume and symptoms after ingestion of maximum tolerable volume of a liquid meal. METHODS: In 36 healthy volunteers, we assessed effects of placebo, 0.5 and 1 mg b.d. alosetron on fasting and postprandial gastric volumes (using single photon emission computed tomography) and symptoms based on 100 mm VAS, 30 min after maximum volume ingested. RESULTS: The 5-HT3 antagonist reduced postprandial symptoms (aggregate score: P < 0.05), nausea (P < 0.001), and tended to reduce bloating (P=0.08). Both 0.5 and 1 mg alosetron reduced nausea (P < 0.025); 1 mg alosetron reduced aggregate symptoms (P < 0.05) and bloating (P < 0.05). Effects on pain (P=0.19) and fullness (P=0.14) were not statistically significant. There were no significant effects of the 5-HT3 antagonist on volume of meal tolerated or on SPECT-measured fasting or postprandial gastric volumes. CONCLUSION: 5-HT3 antagonism reduces aggregate symptoms, nausea and bloating after a liquid meal without increase in gastric volumes, suggesting a role for 5-HT3 in afferent functions in healthy humans during the postprandial period.

Effects of an alpha(2)-adrenergic agonist on gastrointestinal transit, colonic motility, and sensation in humans.

To characterize alpha(2)-adrenergic control of motor and sensory functions of gastrointestinal tract and colon, we studied dose-related effects of clonidine (placebo or up to 0.3 mg po) by random assignment in 55 healthy humans. Gastrointestinal transit was measured in all subjects; in 35, we assessed colonic compliance, tone, and sensations of gas and pain during phasic distensions. Clonidine did not significantly alter gastrointestinal or colonic transit, but it increased colonic compliance and reduced fasting tone without altering colonic response to a meal. Clonidine significantly reduced aggregate sensation to distensions overall and had significant linear dose-related sensory effects at 8- and 24-mmHg distensions. Effect on pain (including dose-response relationship) was due to 0.3-mg dose for distensions at 24 mmHg. We confirmed that clonidine relaxes fasting colonic tone and reduces sensation of pain. In this study, gut transit was not altered by clonidine, and novel dose-response characteristics and clonidine's effect on gas sensation are provided. Doses as low as 0.05 mg may be effective and potentially useful in reducing colonic tone and gas sensation.

Gender-related differences in slowing colonic transit by a 5-HT3 antagonist in subjects with diarrhea-predominant irritable bowel syndrome.

OBJECTIVE: To evaluate the influence of gender on the effect of a 5-HT3 antagonist, alosetron, 1 mg b.i.d., on GI and colonic transit in D-IBS. METHODS: Thirty patients (15 male, 15 female) with D-IBS received 1 mg b.i.d. alosetron for 6 wk. Transit was measured by scintigraphy at baseline and at the end of treatment. RESULTS: Alosetron, 1 mg b.i.d., significantly retarded small bowel and, proximal and overall colonic transit in the 30 patients with D-IBS. The effect of alosetron on the primary endpoint, colonic geometric center at 24 h, was significantly greater in females than in males (p < 0.05). However, two females showed no slowing of colonic transit on treatment. Among male patients, two of 15 had a slowing of colonic transit at 24 h that was greater than the mean change in female patients, suggesting responsiveness to alosetron among a subgroup of males. CONCLUSION: A 5-HT3 antagonist, alosetron, significantly retards small intestinal and colonic transit in diarrhea-predominant IBS patients, with significantly greater female to male responsiveness. Gender partly contributes to differences in the serotonergic control of intestinal and colonic transit in patients with D-IBS.

Validation of a stable isotope gastric emptying test for normal, accelerated or delayed gastric emptying.

To validate a 13C-Spirulina platensis breath test for measurement of accelerated or delayed gastric emptying, we measured gastric emptying of egg containing 13C-S. platensis and 99mTc-sulphur colloid by breath 13 CO2 every 15 min over 3 h and scintigraphy every 15-30 min over 5 h in 57 healthy volunteers. Thirty-three received no treatment, 10 received erythromycin, and 14 atropine. A generalized linear regression model predicted half-emptying time by scintigraphy (t1/2S) from breath 13CO2 (t1/2B) data. Accuracy was assessed by standard deviation (SD) of differences between t1/2S and t1/2B and by receiver operating characteristic (ROC) curves. Regression models using breath samples at baseline, and 45, 90, 105 and 120 min, predicted t1/2B (mean +/- SD) at 118 +/- 59 min, similar to t1/2S (118 +/- 67 min). Correlation between t1/2B and t1/2S was significant (r=0.88; P < 0.0001). Differences between t1/2S and t1/2B were: 18-19.2 min for t1/2 < 70-150 min, and 68.3 min for t1/2 > 150 min. Breath test detected abnormal emptying with a sensitivity of 86% and specificity of 80%. Thus, the 13C-S. platensis test measures gastric emptying t1/2 for solids, which is accelerated or delayed to mimic a range of conditions from dumping syndrome to severe gastroparesis, with high sensitivity and specificity. Additional breath samples are needed to increase sensitivity in detecting accelerated gastric emptying.

Insights into the pathophysiology and mechanisms of constipation, irritable bowel syndrome, and diverticulosis in older people.

OBJECTIVES: To review the epidemiology, pathophysiology and mechanisms of irritable bowel syndrome (IBS), constipation, and diverticulosis, for the purpose of addressing these three common conditions in older adults (>65 years of age). DESIGN: Using a MEDLINE search, we identified original English language journal articles and reviews from 1965 to December 1998. We also selected articles published before 1965 or after 1998 that were cross-referenced or pertinent to the topics researched. RESULTS: The prevalence of constipation and diverticulosis is higher in older than in younger adults. Significant risk factors for constipation in older women are failure of the anorectal angle to open or excessive perineal descent, which represent disturbances of pelvic floor function and rectal evacuation. In contrast, the prevalence of IBS is no greater than in younger adults. Nevertheless, these syndromes impact on the patient's functional status and quality of life. The mechanisms resulting in these gastrointestinal syndromes are unclear. Uncoordinated colonic activity and colonic segmentation may lead to IBS and diverticulosis, respectively, and these pathophysiological findings suggest disorders of inhibitory control of neuromuscular function. The total number of neurons in the myenteric plexus is decreased, and collagen deposited in the distal colon is increased with aging in humans. Animal studies suggest that senescent colonic muscle responds less to excitatory factors in vitro, and neural injury in older animals may result from apoptosis, defects of mitochondrial metabolism, and inadequate levels or response to neurotrophins. Future investigations will reveal whether similar mechanisms underlie human disease. Currently, treatment is aimed at relief of symptoms of IBS or constipation or dealing with the complications of diverticulosis. CONCLUSIONS: Constipation, IBS, and diverticulosis are common problems of aging. There is a need for further systematic research of the basic mechanisms in neuromuscular dysfunction with aging, including the studies of physical characteristics of the colonic wall, pelvic floor function (particularly in women with excessive perineal descent), and neurohormonal control of motility and sensation. Insights on the pathophysiology and mechanisms of neural injury may lead to more specific treatments in the future, e.g., serotonergic agents and neurotrophins. Meanwhile, collaborations between primary care physicians, geriatricians, and gastroenterologists can optimize management of these three common conditions that significantly impact the quality of life of older adults.

Factors affecting corneal strip stroma-to-stroma adhesion.

BACKGROUND: Successful laser in situ keratomileusis depends on strong adhesion between the dissected anterior corneal flap and the underlying stromal bed, without suturing. This study attempts to generate new information about the mechanism of this adhesion. METHODS: Strips of fresh bovine corneal stroma were dissected and split apart. The split strips were then made to adhere to each other with varying amounts of combined heat and drying. A relationship was developed between heat applied and hydration of strips. After each heat and drying treatment, the strips were pulled apart and the force needed to accomplish this task was measured. RESULTS: There was a tight linear correlation between increase in temperature and decrease in water content (R2 = 0.7414) and between decrease in water content and increase in the adhesive force (R2 = 0.3355). CONCLUSION: This model suggests that drying increases stromal-stromal adhesion. We speculate this is due to the increased concentration of surface molecules, which have high ionic charge densities and ionic bonding. A higher concentration of these molecules produces stroma-to-stroma adhesion via ionic bonding.

Fall-related injuries in anticoagulated stroke patients during inpatient rehabilitation.

OBJECTIVE: To compare the frequency and severity of fall-related injuries in anticoagulated patients undergoing rehabilitation after stroke to nonanticoagulated stroke patients undergoing rehabilitation. DESIGN: Retrospective chart review. SETTING: Free-standing rehabilitation hospital. PATIENTS: 264 patients who sustained falls while undergoing intensive inpatient rehabilitation after stroke. MEASUREMENTS: Injuries, categorized as minor (abrasions and bruises) or major (intracranial hemorrhage, fracture, major bleeding). MAIN RESULTS: A total of 400 falls in 264 patients undergoing inpatient stroke rehabilitation were reviewed. One hundred thirty-one falls were sustained by 93 patients receiving anticoagulation, whereas 269 falls were sustained by 175 patients not receiving anticoagulation. In both the anticoagulation group and the control (nonanticoagulated) group, approximately one in five falls resulted in minor injuries (abrasions or bruises). Three fractures occurred, but no major bleeding events or intracranial hemorrhage occurred in either group. CONCLUSIONS: The risk for minor injury secondary to fall is comparable between the two groups, and the risk is low in this setting for hemorrhagic injuries in stroke patients falling while receiving anticoagulation.

Measured versus predicted vertical displacement of the sacrum during gait as a tool to measure biomechanical gait performance.

The vertical displacement of the sacrum during walking is proposed as an estimation of the overall biomechanical performance of walking, independent of cardiopulmonary factors. Vertical sacral displacement during walking was measured using an optoelectronic motion analysis system in 10 normal volunteers at variable speeds. Oxygen consumption was simultaneously measured. The actual vertical displacement of the sacrum, when correlated with body weight, reliably predicted oxygen consumption (r2 = 0.91). The relationship between vertical sacral displacement and oxygen consumption persisted when controlling for the variables, velocity, square of velocity, cadence or stride length, each known to co-vary with cardiopulmonary performance. A mathematic model designed to predict the vertical displacement of the sacrum, based on sacral height and average stride length, was tested. The actual vertical sacral displacement correlated with predicted displacement (r = 0.94). Unilateral immobilization of each subject's knee resulted in a greater average vertical sacral displacement during gait than predicted. Comparing measured with predicted vertical sacral displacement may provide a clinically useful and specific overall assessment of biomechanical gait performance.