Chronic Distention Research Articles

A Novel Role for Biomechanical Forces in the Pathogenesis of Idiopathic Constipation

INTRODUCTION: Chronic constipation is a common gastrointestinal disorder, but an anatomic or physiologic cause is identified in only 5% of patients. Surgery to remove chronically dilated segments of intestine is offered as a last resort. Our goal is to understand how the intestinal microenvironment is affected by biomechanical forces such as chronic distention in idiopathic constipation. METHODS: To evaluate the effects of biomechanical force on the colon, we used 3 models: (1) colon from wildtype mice was cultured ex vivo for 24 hours with and without distention and extracellular matrix–related gene expression was assayed using reverse transcriptase-polymerase chain reaction; (2) an in vivo mouse model of enteric distention was assessed at 7 to 14 days by immunohistochemistry; and (3) human specimens from pediatric patients who underwent colon resections for chronic idiopathic constipation (n = 27) were histologically evaluated to clinically validate our findings (Figure).FigureRESULTS: Ex vivo and in vivo colon under tension demonstrated increased fibrosis compared with control. Tension resulted in significantly decreased expression of antifibrotic Gremlin-1 and increased expression of profibrotic interleukin-1β. Collagens and matrix metalloproteinases were downregulated while laminins were upregulated. Seventy-seven percent of patients with chronic idiopathic constipation displayed dilated and/or redundant colon on imaging. In surgical specimens, 26% had interstitial fibrosis, 33% had muscular hypertrophy, and 15% had myocyte vacuolization. These histologic findings were also seen in distended mouse colon. CONCLUSION: Chronic intestinal distention led to a profibrotic phenotype in all 3 models. We conclude that mechanically sensitive cells may be affected by chronic distention and contribute to intestinal dysfunction in idiopathic constipation.

Cortical Visual Impairment

1. Luis H. Ospina, MD* 1. *Assistant Professor, Pediatric Ophthalmology and Neuro-ophthalmology, Ste-Justine Hospital, University de Montreal, Montreal, Quebec, Canada After completing this article, readers should be able to: 1. Recognize cortical visual impairment (CVI) as an important cause of pediatric visual loss. 2. Identify the most frequent causes of pediatric CVI and, more specifically, understand the role of hypoxia as a cause of central visual damage. 3. Describe the different patterns and implications for future vision of hypoxic central visual damage occurring in preterm compared with term babies. 4. Know the clinical signs suggestive of CVI in children. 5. Discuss the involvement of visual functions other than visual acuity (ie, cognitive visual aspects) in CVI and correlate them with the likely affected neuroanatomic substrates. 6. Explain the value of using a multidisciplinary approach in rehabilitating children who have CVI early in their development. Vision loss caused by central nervous system damage often is referred to as CVI but also may be referred to as cerebral visual impairment or neurologic visual impairment. These terms refer to the fact that the primary defect may not necessarily be limited to the striate (primary visual) cortex and may affect other areas subserving vision, such as the visual associative cortex, optic radiations, and visual attention pathways. Although it is not yet certain which of these three terms best describes the visual deficit, it is clear that use of the label cortical blindness must be abandoned. That term not only evokes negative connotations for the child and the family but is inaccurate because in almost every instance, some degree of residual vision remains, and visual improvement can occur. CVI has become the greatest cause of pediatric visual impairment in developed countries (1)(2)(3)(4)(5) and is becoming increasingly prevalent in developing nations. CVI is a problem of increasing frequency for two primary reasons. First, the progress in neonatal care has resulted in improved survival of …

Corticotropin-Releasing Hormone Receptor 1 Antagonist Blocks Brain–Gut Activation Induced by Colonic Distention in Rats

The corticotropin-releasing hormone receptor 1 mediates stress-induced changes in colonic motor activity and emotion. We tested the hypothesis that pretreatment with JTC-017, a specific corticotropin-releasing hormone receptor 1 antagonist, blocks colorectal distention-induced hippocampal noradrenaline release and visceral perception in rats. We also investigated whether pretreatment with JTC-017 blocks acute or chronic colorectal distention-induced adrenocorticotropic hormone release, anxiety, and stress-induced changes in colonic motility. Rats were pretreated intrahippocampally with alpha-helical corticotropin-releasing hormone (1.25 microg/kg; vehicle), a nonspecific corticotropin-releasing hormone receptor antagonist, or intraperitoneally with JTC-017 (10 mg/kg). Hippocampal noradrenaline release after microdialysis and the frequency of abdominal contractions were measured in response to acute colorectal distention. Plasma adrenocorticotropic hormone levels, anxiety-related behavior, and stress-induced changes in colonic motility were evaluated after acute or chronic colorectal distention followed by exposure to an elevated plus maze. Administration of alpha-helical corticotropin-releasing hormone or JTC-017 significantly attenuated hippocampal noradrenaline release and reduced the frequency of abdominal contractions induced by acute distention. In addition, JTC-017 significantly reduced plasma adrenocorticotropic hormone and anxiety after acute distention. After chronic distention, changes in plasma adrenocorticotropic hormone and anxiety were not significant because of habituation. In contrast, a significant increase in fecal pellet output during the elevated plus maze was observed after chronic distention. This increase in fecal pellet output was blocked by pretreatment with JTC-017. Our results suggest that JTC-017, a specific corticotropin-releasing hormone receptor 1 antagonist, attenuates hippocampal noradrenaline release, visceral perception, adrenocorticotropic hormone release, and anxiety after acute colorectal distention in rats. In addition, JTC-017 blocks stress-induced changes in colonic motility after chronic colorectal distention in rats.

Effect of prolonged gastric distention on lower esophageal sphincter function and gastroesophageal reflux

Objectives Morbidly obese patients treated with an intragastric balloon report a transient increase in gastroesophageal reflux (GER) symptoms. In the present study, we evaluated the underlying mechanisms of GER and examined the effect of prolonged gastric distention on lower esophageal sphincter function. Methods Fasting and postprandial manometric studies were performed in obese subjects (n = 15) before, immediately after, and 10 and 20 wk after placement of a 500-ml water-filled balloon. Results Residual lower esophageal sphincter (LES) pressure after water swallows was not affected after balloon placement, excluding mechanical interaction with sleeve function. Postprandial LES pressure was significantly increased after 10 and 20 wk. GER was increased in the right recumbent position until 10 wk after balloon placement, mainly because of an increased percentage of transient lower esophageal sphincter relaxations (TLESRs) accompanied by GER. TLESRs were the main mechanisms underlying reflux both before and after balloon placement. The rate of TLESRs was increased significantly immediately after introduction of the balloon, returning to baseline values after 20 wk. After balloon placement, reflux episodes were evoked by gastric contractions that were not inhibited by meals. Conclusions Chronic distention by an intragastric balloon increased reflux up to 10 wk after placement because of an increase in the percentage of TLESRs accompanied by a reflux episode. In addition, prolonged balloon distention increased the rate of TLESRs and created a postprandial state even 10 wk after balloon placement. After 20 wk these effects largely resolved, illustrating adaptation to this artificial situation.

Surgical Treatment of Diffuse Pigmented Villonodular Synovitis of the Knee

Twenty-five cases of diffuse pigmented villonodular synovitis of the knee in 23 patients were reviewed to determine the results of surgical treatment. All the cases met strict histologic criteria for diagnosis. Long-term clinical follow-up data (average, 58 months) were available for all patients. One case for a patient who was treated by marginal excision recurred within one year. All other cases (initial and recurrent) were treated by total synovectomy, preserving the functional integrity of the knee. Proximal extensor realignments were performed in patients in which chronic distention had caused a redundancy of retinacular tissues. Adhesions, an early complication in eight patients, responded well to closed manipulation and did not adversely affect long-term functional outcome. The outcome was excellent in seven and good in 16 the patients. Two of the patients have had recurrences but have not had another operation. Using this technique, the recurrence rate (8%) and morbidity are significantly lower than those reported previously.

Pneumocele of the maxillary sinus.

Pneumocele of the maxillary sinus has been observed for the first time, to our knowledge. This abnormality probably resulted from a physiologic block to rapid equilibration of intrasinus air pressure through the major sinus ostium as a result of some abnormality producing a one-way valvular mechanism. Repeated air-trapping secondary to sneezing or autoinflation may have produced chronic distention within the maxillary sinus. Roentgenographic findings include bone dehiscence on plain films or tomograms, a normally aerated or hyperlucent sinus, and expansion of the sinus into its various anatomic recesses.

Influence of chronic distention on myometrial contractile protein

Myometrial contractile protein was studied in chronically distended uteri of ovariectomized and estrogen-treated ovariectomized rabbits. Comparative observations were made on uterine surgical specimens obtained from menstruant, postmenopausal, and term pregnant individuals. The animal data indicate that experimentally produced uterine distention does not cause a preferential increase in uterine actomysin. The presence of myometrial hypertrophy resulting in uterine growth is associated with an increase in total myometrial contractile protein. This change in conjunction with an altered viscosity behavior of the isolated actomyosin could account for the increased contractility that has been reported in chronically distended uteri.1

Uterine motility resulting from inflammatory processes in the myometrium, in the absence of ovarian hormones

A T THE present time it is generally held that one may induce motility of uterine muscle in ovariectomized rabbits in only one way, • 5 namely, by the injection of ovarian follieular hormone or other estrogenic agents. When it was found, however, that suitable degrees of chronic distention of the uterus elicit hypertrophy and hyperplasia of the myometrium of ovariectomized rabbits it seemed likely that one would find motility associated with these structural changes. Although distenti011 did not induce motility, it was found that, in certain experiments ih which inflammatory processes were present, uterine motility was indiuced. The procedures were as follows :

The rate of uterine growth resulting from chronic distention

The rate of uterine growth resulting from chronic distention

The effect of progestin on the growth response of the uterus to chronic distention

The effect of progestin on the growth response of the uterus to chronic distention

Failure to Obtain in Immature Rabbits Uterine Growth by Chronic Distention.

In the course of studying the local growth which takes place in chronically distended uteri in both untreated, ovariectomized rabbits and in progestin-treated rabbits,1-4 12 immature rabbits were employed. In the untreated ovariectomized rabbits, 6 separate distention sites were studied, and compared with undistended areas of the same uteri. Lack of sexual maturity was evidenced by the presence of infantile uteri and small, flat ovaries without macroscopic Graafian follicles. It was found that growth resulting from distention was not obtained in any instance, even though the degrees of distention were similar to those which yielded large growth responses in mature rabbits.2,4In the 9 progestin-treated immature rabbits, 14 distention sites were available. These rabbits received 200 r.u. of oestradiol in oil subcutaneously, and a total of 6.6 rb.u. of progestin in 10 days commencing the third day after the oestradiol was given. Despite the fact that the endometrium in each of these rabbits was well prolifer...